FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wong, JYY De Vivo, I Lin, XH Christiani, DC AF Wong, Jason Y. Y. De Vivo, Immaculata Lin, Xihong Christiani, David C. TI Cumulative PM2.5 Exposure and Telomere Length in Workers Exposed to Welding Fumes SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; PULMONARY RESPONSES; LEAD-EXPOSURE; BONE-MARROW; LIFE-SPAN; EXPRESSION; CELLS; LYMPHOCYTES; TISSUES; MODEL AB Telomeres are genomic structures that reflect both mitotic history and biochemical trauma to the genome. Metals inherent in fine particulate matter (PM2.5) were shown to be genotoxic via oxidative damage. However, few studies investigated the induction time of cumulative PM2.5 exposure on telomere length in a longitudinal setting. Therefore, the purpose of this study was to assess the association between occupational PM2.5 exposure in various time windows and telomere length. The study population consisted of 48 boilermakers and the follow-up period was 8 yr. The main exposures were cumulative occupational PM2.5 in the month, year, and career prior to each blood draw, assessed via work history questionnaires and area air measures. Repeated telomere length measurements from leukocytes were assessed via real-time qualitative polymerase chain reaction (qPCR). Analysis was performed using linear mixed models controlling for confounders and white blood cell differentials. Cumulative PM2.5 exposure was treated continuously and categorized into quartiles, in separate analyses. At any follow-up time, for each milligram per cubic meter per hour increase in cumulative PM2.5 exposure in the prior month, there was a statistically significant decrease in relative telomere length of -0.04 units. When categorizing the exposure into quartiles, there was a significant negative association between telomere length and highest quartile of cumulative PM2.5 exposure in the prior month (-0.16). These findings suggest that genomic trauma to leukocyte telomeres was more consistent with recent occupational PM2.5 exposure, as opposed to cumulative exposure extending into the distant past. C1 [Wong, Jason Y. Y.; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wong, Jason Y. Y.; 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 02115 USA. RP Wong, JYY (reprint author), Harvard Univ, Sch Publ Hlth, Bldg 2,Room 247,677 Huntington Ave, 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] FX This project was made possible by funding from the National Institute of Environmental Health Sciences (NIEHS) grants R01ES009860 and P50ES00002. This study was approved by the Institutional Review Board of Harvard School of Public Health (OHRA Protocol P10444, Cardiopulmonary Response to Particulate Exposure, PI David C. Christiani). Informed consent was obtained for all subjects prior to inclusion in the study. The authors declare no conflicts of interest. We thank Shona Fang, Jinming Zhang, Rachel Grashow, and Angela Fan for analytical support. In addition, this project would not be possible without laboratory support from Li Su and Lauren Cassidy. Lastly, we extend our gratitude to Dr. Donna Spiegelman and Zhonghua Liu for their statistical insights. NR 48 TC 8 Z9 9 U1 1 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1528-7394 EI 1087-2620 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD APR 18 PY 2014 VL 77 IS 8 BP 441 EP 455 DI 10.1080/15287394.2013.875497 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AE5NC UT WOS:000334034900003 PM 24627998 ER PT J AU Heaton, JT Sheu, SH Hohman, MH Knox, CJ Weinberg, JS Kleiss, IJ Hadlock, TA AF Heaton, James T. Sheu, Shu Hsien Hohman, Marc H. Knox, Christopher J. Weinberg, Julie S. Kleiss, Ingrid J. Hadlock, Tessa A. TI RAT WHISKER MOVEMENT AFTER FACIAL NERVE LESION: EVIDENCE FOR AUTONOMIC CONTRACTION OF SKELETAL MUSCLE SO NEUROSCIENCE LA English DT Article DE autonomic; infraorbital nerve; motor; paralysis; parasympathetic; reinnervation ID VASOACTIVE INTESTINAL POLYPEPTIDE; CUTANEOUS BLOOD-VESSELS; SENSORY PROTECTION; DENERVATED MUSCLE; MYSTACIAL PAD; STRIATED-MUSCLE; PARASYMPATHETIC INNERVATION; FUNCTIONAL-SIGNIFICANCE; CLINICAL-IMPLICATIONS; RHYTHMIC WHISKING AB Vibrissal whisking is often employed to track facial nerve regeneration in rats; however, we have observed similar degrees of whisking recovery after facial nerve transection with or without repair. We hypothesized that the source of non-facial nerve-mediated whisker movement after chronic denervation was from autonomic, cholinergic axons traveling within the infraorbital branch of the trigeminal nerve (ION). Rats underwent unilateral facial nerve transection with repair (N = 7) or resection without repair (N = 11). Post-operative whisking amplitude was measured weekly across 10 weeks, and during intraoperative stimulation of the ION and facial nerves at >= 18 weeks. Whisking was also measured after subsequent ION transection (N = 6) or pharmacologic blocking of the autonomic ganglia using hexamethonium (N = 3), and after snout cooling intended to elicit a vasodilation reflex (N = 3). Whisking recovered more quickly and with greater amplitude in rats that underwent facial nerve repair compared to resection (P < 0.05), but individual rats overlapped in whisking amplitude across both groups. In the resected rats, non-facial-nerve-mediated whisking was elicited by electrical stimulation of the ION, temporarily diminished following hexamethonium injection, abolished by transection of the ION, and rapidly and significantly (P < 0.05) increased by snout cooling. Moreover, fibrillation-related whisker movements decreased in all rats during the initial recovery period (indicative of reinnervation), but re-appeared in the resected rats after undergoing ION transection (indicative of motor denervation). Cholinergic, parasympathetic axons traveling within the ION innervate whisker pad vasculature, and immunohistochemistry for vasoactive intestinal peptide revealed these axons branching extensively over whisker pad muscles and contacting neuromuscular junctions after facial nerve resection. This study provides the first behavioral and anatomical evidence of spontaneous autonomic innervation of skeletal muscle after motor nerve lesion, which not only has implications for interpreting facial nerve reinnervation results, but also calls into question whether autonomic-mediated innervation of striated muscle occurs naturally in other forms of neuropathy. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Heaton, James T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sheu, Shu Hsien] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. [Hohman, Marc H.; Knox, Christopher J.; Weinberg, Julie S.; Kleiss, Ingrid J.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Kleiss, Ingrid J.] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol & Head & Neck Surg, NL-6525 ED Nijmegen, Netherlands. RP Heaton, JT (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, One Bowdoin Sq,Floor 11, Boston, MA 02114 USA. EM james.heaton@mgh.harvard.edu OI Sheu, Shu-Hsien/0000-0003-0758-4654 FU [R01NS071067] FX This work was supported by R01NS071067 to T.A. Hadlock and J.T. Heaton. The authors thank Jeff Lichtman, M.D., Ph.D. for the generous use of his immunohistochemistry lab, and James B. Kobler, Ph.D. for his insightful suggestions regarding the methods used to demonstrate autonomic neural control. NR 70 TC 3 Z9 3 U1 0 U2 7 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 APR 18 PY 2014 VL 265 BP 9 EP 20 DI 10.1016/j.neuroscience.2014.01.038 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AE6UV UT WOS:000334134400002 PM 24480367 ER PT J AU Clark, KB AF Clark, Kevin B. TI Basis for a neuronal version of Grover's quantum algorithm SO FRONTIERS IN MOLECULAR NEUROSCIENCE LA English DT Article DE biotechnology; calcium-induced calcium reactions (CICRs); cellular decision making; classical and quantum computation; inositol 1,4,5-trisphosphate receptors (IP(3)Rs); intracellular calcium; neuronal plasticity; quantum molecular networks and memory ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CA2+ RELEASE CHANNELS; ENDOPLASMIC-RETICULUM; SYNAPTIC PLASTICITY; CALCIUM WAVES; IP3 RECEPTORS; TRISPHOSPHATE RECEPTORS; LANDAUERS PRINCIPLE; FACTORING ALGORITHM; MATHEMATICAL-THEORY AB Grover's quantum (search) algorithm exploits principles of quantum information theory and computation to surpass the strong Church-Turing limit governing classical computers. The algorithm initializes a search field into superposed N (eigen)states to later execute nonclassical "subroutines" involving unitary phase shifts of measured states and to produce root-rate or quadratic gain in the algorithmic time (O(N-1/2)) needed to find some "target" solution m. Akin to this fast technological search algorithm, single eukaryotic cells, such as differentiated neurons, perform natural quadratic speed-up in the search for appropriate store-operated Ca2+ response regulation of, among other processes, protein and lipid biosynthesis, cell energetics, stress responses, cell fate and death, synaptic plasticity, and immunoprotection. Such speed-up in cellular decision making results from spatiotemporal dynamics of networked intracellular Ca2+-induced Ca2+ release and the search (or signaling) velocity of Ca2+ wave propagation. As chemical processes, such as the duration of Ca2+ mobilization, become rate-limiting over interstore distances, Ca2+ waves quadratically decrease interstore-travel time from slow saltatory to fast continuous gradients proportional to the square-root of the classical Ca2+ diffusion coefficient, D-1/2, matching the computing efficiency of Grover's quantum algorithm. In this Hypothesis and Theory article, I elaborate on these traits using a fire-diffuse-fire model of store-operated cytosolic Ca2+ signaling valid for glutamatergic neurons. Salient model features corresponding to Grover's quantum algorithm are parameterized to meet requirements for the Oracle Hadamard transform and Grover's iteration. A neuronal version of Grover's quantum algorithm figures to benefit signal coincidence detection and integration, bidirectional synaptic plasticity, and other vital cell functions by rapidly selecting, ordering, and/or counting optional response regulation choices. C1 [Clark, Kevin B.] Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA USA. [Clark, Kevin B.] Complex Biol Syst Alliance, N Andover, MA USA. RP Clark, KB (reprint author), 4229 SE Harney St, Portland, OR 97206 USA. EM kbclarkphd@yahoo.com NR 177 TC 1 Z9 1 U1 0 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5099 J9 FRONT MOL NEUROSCI JI Front. Molec. Neurosci. PD APR 17 PY 2014 VL 7 AR 29 DI 10.3389/fnmol.2014.00029 PG 20 WC Neurosciences SC Neurosciences & Neurology GA AZ0YX UT WOS:000347968800001 PM 24860419 ER PT J AU Friedman, LS Simmons, LH Goldman, RH Sohani, AR AF Friedman, Lawrence S. Simmons, Leigh H. Goldman, Rose H. Sohani, Aliyah R. TI Case 12-2014: A 59-Year-Old Man with Fatigue, Abdominal Pain, Anemia, and Abnormal Liver Function SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLOOD LEAD; HEMOCHROMATOSIS; ASSOCIATION; PORPHYRIAS; POPULATION; EXPOSURE; GENE AB A 59-year-old man was admitted to the hospital because of fatigue, abdominal pain, new anemia, arthralgias, abnormal liver function, and emotional lability. A peripheral-blood smear showed polychromasia and coarse basophilic stippling of erythrocytes. Presentation of CaseDr. Laura D. Flannery (Medicine): A 59-year-old man was seen in an outpatient clinic at this hospital because of fatigue, abdominal pain, anemia, arthralgias, and abnormal liver function. The patient had been in his usual state of health until approximately 3 days before presentation, when epigastric distress and ankle edema occurred. He also reported increased personal stress, difficulty sleeping, dysgeusia, and nausea. On presentation in an outpatient clinic at this hospital, he reported epigastric pain that he rated at 6 on a scale of 0 to 10 (with 10 indicating the most severe pain) and no weight ... C1 [Friedman, Lawrence S.; Simmons, Leigh H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Friedman, Lawrence S.; Simmons, Leigh H.; Goldman, Rose H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA USA. [Goldman, Rose H.] Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU New England Research Institutes FX Dr. Simmons reports receiving consulting fees from the New England Research Institutes, and Dr. Goldman serving as a paid expert witness in legal cases related to occupational and environmental health. No other potential conflict of interest relevant to this article was reported. NR 25 TC 6 Z9 7 U1 0 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 APR 17 PY 2014 VL 370 IS 16 BP 1542 EP 1550 DI 10.1056/NEJMcpc1314242 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AF3HE UT WOS:000334601600012 PM 24738672 ER PT J AU Lobry, C Oh, P Mansour, MR Look, AT Aifantis, I AF Lobry, Camille Oh, Philmo Mansour, Marc R. Look, A. Thomas Aifantis, Iannis TI Notch signaling: switching an oncogene to a tumor suppressor SO BLOOD LA English DT Review ID HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; MURINE ERYTHROLEUKEMIA-CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; SCFFBW7 UBIQUITIN LIGASE; MARGINAL ZONE LYMPHOMA; F-BOX PROTEIN; SELF-RENEWAL AB The Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types. Notch is a binary cell-fate determinant, and its hyper-activation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL). Recently, several studies also unraveled tumor-suppressor roles for Notch signaling in different tissues, including tissues where it was before recognized as an oncogene in specific lineages. Whereas involvement of Notch as an oncogene in several lymphoid malignancies (T-ALL, B-chronic lymphocytic leukemia, splenic marginal zone lymphoma) is well characterized, there is growing evidence involving Notch signaling as a tumor suppressor in myeloid malignancies. It therefore appears that Notch signaling pathway's oncogenic or tumor-suppressor abilities are highly context dependent. In this review, we summarize and discuss latest advances in the understanding of this dual role in hematopoiesis and the possible consequences for the treatment of hematologic malignancies. C1 [Lobry, Camille; Oh, Philmo; Aifantis, Iannis] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. [Lobry, Camille; Oh, Philmo; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Lobry, Camille; Oh, Philmo; Aifantis, Iannis] NYU, Inst Canc, New York, NY 10016 USA. [Lobry, Camille; Oh, Philmo; Aifantis, Iannis] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Stem Cell Biol, New York, NY 10016 USA. [Mansour, Marc R.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mansour, Marc R.] UCL, Dept Haematol, Inst Canc, London, England. [Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Aifantis, I (reprint author), NYU, Sch Med, 550 1st Ave, New York, NY 10016 USA. EM camille.lobry@nyumc.org; iannis.aifantis@nyumc.org RI lobry, camille/A-6188-2015 OI lobry, camille/0000-0003-0550-4921 FU Research Project Grant Program of the National Cancer Institute [RO1CA173636, RO1CA133379, RO1CA105129, RO1CA149655]; Leukemia & Lymphoma Society; V Foundation for Cancer Research; William Lawrence and Blanche Hughes Foundation; St. Baldrick's Foundation for Cancer Research; New York University Medical Scientist Training Program; Helen and Martin Kimmel Center for Stem Cell Research; Kay Kendall Leukaemia Fund of the United Kingdom; Claudia Adams Barr foundation of the Dana Farber Cancer Institute; National Cancer Institute [5P01CA109901, 1R01CA176746, P30CA06516]; Alex's Lemonade Stand; Team Path To the Cure grant FX I.A. is supported by the National Institutes of Health, Research Project Grant Program of the National Cancer Institute (RO1CA173636, RO1CA133379, RO1CA105129, and RO1CA149655), the Leukemia & Lymphoma Society (Translational Research Program grants), The V Foundation for Cancer Research, the William Lawrence and Blanche Hughes Foundation, and the St. Baldrick's Foundation for Cancer Research. P.O. was supported by the New York University Medical Scientist Training Program. C. L. was supported by the Helen and Martin Kimmel Center for Stem Cell Research and is currently a Leukemia and Lymphoma Society Fellow. M. R. M. is supported by the Kay Kendall Leukaemia Fund of the United Kingdom, a Team Path To the Cure grant, and the Claudia Adams Barr foundation of the Dana Farber Cancer Institute. A. T. L. is supported by grants from the National Cancer Institute (5P01CA109901, 1R01CA176746, and P30CA06516) and by grants from the William Lawrence and Blanche Hughes Foundation and Alex's Lemonade Stand. I. A. is a Howard Hughes Medical Institute Early Career Scientist. NR 129 TC 65 Z9 71 U1 2 U2 32 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 17 PY 2014 VL 123 IS 16 BP 2451 EP 2459 DI 10.1182/blood-2013-08-355818 PG 9 WC Hematology SC Hematology GA AH1PX UT WOS:000335894500010 PM 24608975 ER PT J AU Moulton, EA Becerra, L Johnson, A Burstein, R Borsook, D AF Moulton, Eric A. Becerra, Lino Johnson, Adriana Burstein, Rami Borsook, David TI Altered Hypothalamic Functional Connectivity with Autonomic Circuits and the Locus Coeruleus in Migraine SO PLOS ONE LA English DT Article ID TEMPORAL POLE; RESPONSES; BRAIN; PAIN; METAANALYSIS; ACTIVATION; SYSTEM; CORTEX; SLEEP; PART AB The hypothalamus has been implicated in migraine based on the manifestation of autonomic symptoms with the disease, as well as neuroimaging evidence of hypothalamic activation during attacks. Our objective was to determine functional connectivity (FC) changes between the hypothalamus and the rest of the brain in migraine patients vs. control subjects. This study uses fMRI (functional magnetic resonance imaging) to acquire resting state scans in 12 interictal migraine patients and 12 healthy matched controls. Hypothalamic connectivity seeds were anatomically defined based on high-resolution structural scans, and FC was assessed in the resting state scans. Migraine patients had increased hypothalamic FC with a number of brain regions involved in regulation of autonomic functions, including the locus coeruleus, caudate, parahippocampal gyrus, cerebellum, and the temporal pole. Stronger functional connections between the hypothalamus and brain areas that regulate sympathetic and parasympathetic functions may explain some of the hypothalamic-mediated autonomic symptoms that accompany or precede migraine attacks. C1 [Moulton, Eric A.; Becerra, Lino; Johnson, Adriana; Borsook, David] Harvard Univ, Sch Med, Ctr Pain & Brain, Dept Anesthesia,Boston Childrens Hosp,Pain Analge, Waltham, MA 02138 USA. [Becerra, Lino; Borsook, David] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Borsook, David] Harvard Univ, McLean Hosp, Sch Med, Ctr Pain & Brain,Dept Psychiat,PAIN Grp, Belmont, MA USA. [Burstein, Rami] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Moulton, EA (reprint author), Harvard Univ, Sch Med, Ctr Pain & Brain, Dept Anesthesia,Boston Childrens Hosp,Pain Analge, Waltham, MA 02138 USA. EM eric.moulton@childrens.harvard.edu FU National Institutes of Health [R01NS073997, K24NS0624050]; L Herlands fund FX This work was supported by the National Institutes of Health (R01NS073997 to D. B., K24NS0624050 to D. B.); the L Herlands fund to the P.A.I.N. Group (D. B., L. B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 17 Z9 18 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 APR 17 PY 2014 VL 9 IS 4 AR e95508 DI 10.1371/journal.pone.0095508 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AG3IK UT WOS:000335309100131 PM 24743801 ER PT J AU Joller, N Lozano, E Burkett, PR Patel, B Xiao, S Zhu, C Xia, JR Tan, TG Sefik, E Yajnik, V Sharpe, AH Quintana, FJ Mathis, D Benoist, C Hafler, DA Kuchroo, VK AF Joller, Nicole Lozano, Ester Burkett, Patrick R. Patel, Bonny Xiao, Sheng Zhu, Chen Xia, Junrong Tan, Tze G. Sefik, Esen Yajnik, Vijay Sharpe, Arlene H. Quintana, Francisco J. Mathis, Diane Benoist, Christophe Hafler, David A. Kuchroo, Vijay K. TI Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses SO IMMUNITY LA English DT Article ID REGULATORY T-CELLS; AIRWAY INFLAMMATION; FOXP3; DIFFERENTIATION; INTERLEUKIN-23; RESOLUTION; RECEPTOR; PROMOTE; PROTEIN; T(H)17 AB Foxp3(+) T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3(+) T cells expressing the coinhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses proinflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT(+) Treg cells as an activated Treg cell subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg-cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses. C1 [Joller, Nicole; Burkett, Patrick R.; Patel, Bonny; Xiao, Sheng; Zhu, Chen; Xia, Junrong; Quintana, Francisco J.; Kuchroo, Vijay K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Lozano, Ester; Hafler, David A.] Yale Univ, Sch Med, Dept Neurol & Immunobiol, New Haven, CT 06520 USA. [Burkett, Patrick R.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA. [Sefik, Esen; Sharpe, Arlene H.; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Yajnik, Vijay] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sharpe, Arlene H.; Kuchroo, Vijay K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kuchroo, Vijay K.] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. RP Kuchroo, VK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. EM vkuchroo@rics.bwh.harvard.edu RI Lozano, Ester/H-2215-2014; Joller, Nicole/G-7897-2015 OI Lozano, Ester/0000-0002-6307-9807; Joller, Nicole/0000-0003-1996-1672 FU NIH [P01AI056299, P01AI039671, P01AI073748, R01NS045937, 5T32HL007633, K01DK090105, AI075285, AI09390]; National Multiple Sclerosis Society [RG4111A1, RG2751]; Swiss Multiple Sclerosis Society; Arthritis National Research Foundation; AGAUR-Government of Catalonia FX We would like to thank G. Levi for the Fgl2 reagents and KO mice, Zymogenetics for mice and reagents, D. Kozoriz for cell sorting, J. Sullivan for technical assistance, and members of the V. K. K. group, especially A. Peters, for discussions. This work was supported by grants P01AI056299 (to V. K. K., A. H. S., and C. B.), P01AI039671 (to V. K. K., D. A. H., and A. H. S.), P01AI073748, R01NS045937 (to V. K. K.), 5T32HL007633 (to P. R. B.), K01DK090105 (to S. X.), and AI075285 and AI093903 (to F. J. Q.) from NIH and by RG4111A1 (to F. J. Q.) and RG2751 (to V. K. K.) from the National Multiple Sclerosis Society. N.J. is supported by the Swiss Multiple Sclerosis Society and the Arthritis National Research Foundation. E. L. is recipient of a Postdoctoral Scholarship in the Beatriu de Pinos Programme (2011-2013) (AGAUR-Government of Catalonia). V. K. K. is a founder of, and has a financial interest in, Tempero Pharmaceuticals. V.K.K.'s interests were reviewed and are managed by the Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. NR 33 TC 85 Z9 87 U1 3 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD APR 17 PY 2014 VL 40 IS 4 BP 569 EP 581 DI 10.1016/j.immuni.2014.02.012 PG 13 WC Immunology SC Immunology GA AF6UF UT WOS:000334849400014 PM 24745333 ER PT J AU Goto, Y Panea, C Nakato, G Cebula, A Lee, C Diez, MG Laufer, TM Ignatowicz, L Ivanov, II AF Goto, Yoshiyuki Panea, Casandra Nakato, Gaku Cebula, Anna Lee, Carolyn Diez, Marta Galan Laufer, Terri M. Ignatowicz, Leszek Ivanov, Ivaylo I. TI Segmented Filamentous Bacteria Antigens Presented by Intestinal Dendritic Cells Drive Mucosal Th17 Cell Differentiation SO IMMUNITY LA English DT Article ID REGULATORY T-CELLS; CLASS-II MOLECULES; COMMENSAL BACTERIA; EPITHELIAL-CELLS; LAMINA PROPRIA; DEFICIENT MICE; IMMUNE-SYSTEM; CHAIN GENE; HOMEOSTASIS; MICROBIOTA AB How commensal microbiota contributes to immune cell homeostasis at barrier surfaces is poorly understood. Lamina propria (LP) T helper 17 (Th17) cells participate in mucosal protection and are induced by commensal segmented filamentous bacteria (SFB). Here we show that MHCII-dependent antigen presentation of SFB antigens by intestinal dendritic cells (DCs) is crucial for Th17 cell induction. Expression of MHCII on CD11c(+) cells was necessary and sufficient for SFB-induced Th17 cell differentiation. Most SFB-induced Th17 cells recognized SFB in an MHCII-dependent manner. SFB primed and induced Th17 cells locally in the LP and Th17 cell induction occurred normally in mice lacking secondary lymphoid organs. The importance of other innate cells was unveiled by the finding that MHCII deficiency in group 3 innate lymphoid cells (ILCs) resulted in an increase in SFB-independent Th17 cell differentiation. Our results outline the complex role of DCs and ILCs in the regulation of intestinal Th17 cell homeostasis. C1 [Goto, Yoshiyuki; Panea, Casandra; Nakato, Gaku; Lee, Carolyn; Diez, Marta Galan; Ivanov, Ivaylo I.] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA. [Cebula, Anna; Ignatowicz, Leszek] Georgia Regents Univ, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA. [Laufer, Terri M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Ivanov, II (reprint author), Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA. EM ii2137@columbia.edu FU National Institute of Health [1R01DK098378]; Crohn's and Colitis Foundation of America SRA [259540]; Toyobo Biofoundation; Pew Charitable Trust FX We thank members of the I. I. I. laboratory for their help in all aspects of the project. We thank Yoshinori Umesaki at the Yakult Central Institute for providing feces from SFB-monocolonized mice. We thank Kenya Honda and Seiko Narushima for developing and sharing the SFB sorting protocol. We thank Steve Reiner and Boris Reizis for reading the manuscript and for invaluable scientific discussions. We thank Siu-Hong Ho at the Columbia Center for Translational Immunology Flow Cytometry Core and Amir Figueroa at the Department of Microbiology and Immunology Flow Cytometry Core for help with sorting. This work was supported by the National Institute of Health 1R01DK098378 to I. I. I. and by the Crohn's and Colitis Foundation of America SRA#259540 to I. I. I. G.N. was supported by a long-term research grant from Toyobo Biofoundation. I. I. I. is a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trust. NR 49 TC 116 Z9 121 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD APR 17 PY 2014 VL 40 IS 4 BP 594 EP 607 DI 10.1016/j.immuni.2014.03.005 PG 14 WC Immunology SC Immunology GA AF6UF UT WOS:000334849400016 PM 24684957 ER PT J AU Liu, Y Samuel, BS Breen, PC Ruvkun, G AF Liu, Ying Samuel, Buck S. Breen, Peter C. Ruvkun, Gary TI Caenorhabditis elegans pathways that surveil and defend mitochondria SO NATURE LA English DT Article ID UNFOLDED PROTEIN RESPONSE; C-ELEGANS; CERAMIDE SYNTHASE; APOPTOSIS; ACTIVATION; LONGEVITY; STRESS; UPR AB Mitochondrial function is challenged by toxic by-products of metabolism as well as by pathogen attack(1,2). Caenorhabditis elegans normally responds to mitochondrial dysfunction with activation of mitochondrial-repair, drug-detoxification and pathogen-response pathways(1-7). Here, from a genome-wide RNA interference (RNAi) screen, we identified 45 C. elegans genes that are required to upregulate detoxification, pathogen-response and mitochondrial-repair pathways after inhibition of mitochondrial function by drug-induced or genetic disruption. Animals defective in ceramide biosynthesis are deficient in mitochondrial surveillance, and addition of particular ceramides can rescue the surveillance defects. Ceramide can also rescue the mitochondrial surveillance defects of other gene inactivations, mapping these gene activities upstream of ceramide. Inhibition of the mevalonate pathway, either by RNAi or statin drugs, also disrupts mitochondrial surveillance. Growth of C. elegans with a significant fraction of bacterial species from their natural habitat causes mitochondrial dysfunction. Other bacterial species inhibit C. elegans defence responses to a mitochondrial toxin, revealing bacterial countermeasures to animal defence. C1 [Liu, Ying; Samuel, Buck S.; Breen, Peter C.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Liu, Ying; Samuel, Buck S.; Breen, Peter C.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Samuel, Buck/0000-0002-4347-3997 FU Helen Hay Whitney research fellowship; Charles King Trust postdoctoral fellowship; National Institutes of Health [NIH AG043184-16] FX We thank C. Haynes (Memorial Sloan Kettering Cancer Center), F. Ausubel (Massachusetts General Hospital) and the Caenorhabditis Genetics Center for providing strains; and the V. Mootha laboratory (Massachusetts General Hospital) for providing C2C12 cells. We thank J. Larkins-Ford, C. Phillips, S. Garcia and M. Pellegrino for technical support, as well as M. A. Felix for bacterial strains and for guidance in the collection of microbial strains from C. elegans natural habitats. Y.L. is supported by the Helen Hay Whitney research fellowship; B.S.S. is supported by the Charles King Trust postdoctoral fellowship. The work is supported by a grant from the National Institutes of Health, awarded to G.R. (NIH AG043184-16). NR 24 TC 60 Z9 60 U1 3 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 17 PY 2014 VL 508 IS 7496 BP 406 EP + DI 10.1038/nature13204 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AF0KP UT WOS:000334403000054 PM 24695221 ER PT J AU Polly, P Tan, TC AF Polly, Patsie Tan, Timothy C. TI The role of vitamin D in skeletal and cardiac muscle function SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE cytokines; cancer cachexia; skeletal muscle; cardiac muscle and transcriptome ID EXPERIMENTAL CANCER CACHEXIA; D-RECEPTOR VDR; QUALITY-OF-LIFE; MOLECULAR-MECHANISMS; 1,25-DIHYDROXYVITAMIN-D3 RECEPTORS; RETINOBLASTOMA PROTEIN; PARATHYROID-HORMONE; INSULIN-RESISTANCE; HEART-FAILURE; KNOCKOUT MICE AB Myopathy is a feature of many inflammatory syndromes. Chronic inflammation has been linked to pathophysiological mechanisms which implicate 1,25 dihydroxyvitamin D-3 (1,25-(OH)(2)D-3)-mediated signaling pathways with emerging evidence supporting a role for the vitamin D receptor (VDR) in contractile and metabolic function of both skeletal and cardiac muscle. Altered VDR expression in skeletal and cardiac muscle has been reported to result in significant effects on metabolism, calcium signaling and fibrosis in these tissues. Elevated levels of serum inflammatory cytokines, such as IL-6, TNF-alpha and IFN gamma, have been shown to impact myogenic and nuclear receptor signaling pathways in cancer-induced cachexia. The dysregulation of nuclear receptors, such as VDR and RXR alpha in muscle cells, has also been postulated to result in myopathy via their effects on muscle structural integrity and metabolism. Future research directions include generating transcriptome-wide information incorporating VDR and its gene targets and using systems biology approaches to identify altered molecular networks in human tissues such as muscle. These approaches will aid in the development of novel therapeutic targeting strategies for inflammation-induced myopathies. C1 [Polly, Patsie; Tan, Timothy C.] UNSW Australia, Fac Med, Sch Med Sci, Inflammat & Infect Res Ctr, Kensington, NSW 2052, Australia. [Polly, Patsie] UNSW Australia, Fac Med, Sch Med Sci, Dept Pathol, Kensington, NSW 2052, Australia. [Tan, Timothy C.] Massachusetts Gen Hosp, Dept Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Polly, P (reprint author), UNSW Australia, Fac Med, Sch Med Sci, Dept Pathol, Rm 420 Wallace Wurth East Bldg, Kensington, NSW 2052, Australia. EM patsie.polly@unsw.edu.au NR 89 TC 3 Z9 3 U1 2 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PD APR 16 PY 2014 VL 5 AR 146 DI 10.3389/fphys.2014.00146 PG 7 WC Physiology SC Physiology GA AX6MX UT WOS:000347037300001 ER PT J AU Marinkovic, K Rosen, BQ Cox, B Hagler, DJ AF Marinkovic, Ksenija Rosen, Burke Q. Cox, Brendan Hagler, Donald J., Jr. TI Spatio-temporal processing of words and nonwords: Hemispheric laterality and acute alcohol intoxication SO BRAIN RESEARCH LA English DT Article DE Reading; Anatomically-constrained MEG; ERP; N400; Lexical decision; Pseudoword ID ANTEROVENTRAL TEMPORAL-LOBE; ANTERIOR CINGULATE CORTEX; DEPTH-RECORDED POTENTIALS; EVENT-RELATED POTENTIALS; SURFACE-BASED ANALYSIS; MEDIAL FRONTAL-CORTEX; CORTICAL SURFACE; LEXICAL DECISION; SEMANTIC MEMORY; LANGUAGE COMPREHENSION AB This study examined neurofunctional correlates of reading by modulating semantic, lexical, and orthographic attributes of letter strings. It compared the spatio-temporal activity patterns elicited by real words (RW), pseudowords, Orthographically regular, pronounceable nonwords (PN) that carry no meaning, and orthographically illegal, nonpronounceable nonwords (NN). A double-duty lexical decision paradigm instructed participants to detect RW while ignoring nonwords and to additionally respond to words that refer to animals (AW). Healthy social drinkers (N=22) participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. Whole-head MEG signals were analyzed with an anatomically-constrained MEG method. Simultaneously acquired ERPs confirm previous evidence. Spatio-temporal MEG estimates to RW and PN are consistent with the highly replicable left-lateralized ventral visual processing stream. However, the PN elicit weaker activity than other stimuli starting at similar to 230 ms and extending to the M400 (magnetic equivalent of N400) in the left lateral temporal area, indicating their reduced access to lexicosemantic stores. In contrast, the NN uniquely engage the right hemisphere during the M400. Increased demands on lexicosemantic access imposed by AW result in greater activity in the left temporal cortex starting at similar to 230 ms and persisting through the M400 and response preparation stages. Alcohol intoxication strongly attenuates early visual responses occipito-temporally overall. Subsequently, alcohol selectively affects the left prefrontal cortex as a function of orthographic and semantic dimensions, suggesting that it modulates the dynamics of the lexicosemantic processing in a top-down manner, by increasing difficulty of semantic retrieval. (C) 2014 The Authors. Published by Elsevier B.V. C1 [Marinkovic, Ksenija; Rosen, Burke Q.; Hagler, Donald J., Jr.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Marinkovic, Ksenija; Cox, Brendan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. RP Marinkovic, K (reprint author), Univ Calif San Diego, Dept Radiol, 9500 Gilman Dr,0841, La Jolla, CA 92093 USA. EM xenia@ucsd.edu FU National Institutes of Health [K01-AA13402, R01-AA016624, K01-MH079146, RR031599]; MIND Institute FX This research was supported by Funds from the National Institutes of Health (K01-AA13402 and R01-AA016624 (to KM), K01-MH079146 (to DJH), RR031599), and MIND Institute. The data were collected at Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA. We thank Jonathan Dan, Jason Sherfey, and Sanja Kovacevic for assistance. NR 134 TC 3 Z9 3 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD APR 16 PY 2014 VL 1558 BP 18 EP 32 DI 10.1016/j.brainres.2014.02.030 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AG5AJ UT WOS:000335431200003 PM 24565928 ER PT J AU Gilman, JM Kuster, JK Lee, S Lee, MJ Kim, BW Makris, N van der Kouwe, A Blood, AJ Breiter, HC AF Gilman, Jodi M. Kuster, John K. Lee, Sang Lee, Myung Joo Kim, Byoung Woo Makris, Nikos van der Kouwe, Andre Blood, Anne J. Breiter, Hans C. TI Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cannabis; gray matter density; marijuana; multimodal imaging; reward; topology/shape ID PREFRONTAL CORTEX; HUMAN BRAIN; COLLEGE-STUDENTS; DRUG-USE; COCAINE; ALCOHOL; SCHIZOPHRENIA; MARIJUANA; SHAPE; MORPHOMETRY AB Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Delta 9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization. C1 [Gilman, Jodi M.; Kuster, John K.; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Blood, Anne J.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Lab Neuroimaging & Genet, Charlestown, MA 02129 USA. [Kuster, John K.; Blood, Anne J.; Breiter, Hans C.] Massachusetts Gen Hosp, Mood & Motor Control Lab, Charlestown, MA 02129 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Psychiat, Charlestown, MA 02129 USA. [Gilman, Jodi M.; van der Kouwe, Andre; Blood, Anne J.; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gilman, Jodi M.; Makris, Nikos; van der Kouwe, Andre; Blood, Anne J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Breiter, Hans C.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Warren Wright Adolescent Ctr, Chicago, IL 60611 USA. RP Breiter, HC (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Warren Wright Adolescent Ctr, 710 N Lake Shore Dr,Abbott Hall 1301, Chicago, IL 60611 USA. EM h-breiter@northwestern.edu FU National Institute on Drug Abuse [14118, 026002, 026104, 027804, 034093]; Office of National Drug Control Policy; Counterdrug Technology Assessment Center [DABK39-03-0098, DABK39-03-C-0098]; National Institute of Neurological Disorders and Stroke, National Institutes of Health [052368]; Warren Wright Adolescent Center at Northwestern Memorial Hospital; Northwestern University, Chicago; Harvard Medical School Norman E. Zinberg Fellowship in Addiction Psychiatry Research FX This work was supported by the National Institute on Drug Abuse (Grants 14118, 026002, 026104, and 027804 to H. C. B. and Grant 034093 to J.M.G.), the Office of National Drug Control Policy, Counterdrug Technology Assessment Center (Grants DABK39-03-0098 and DABK39-03-C-0098), and the National Institute of Neurological Disorders and Stroke, National Institutes of Health (Grant 052368 to A.J.B.). H. C. B. was also supported by the Warren Wright Adolescent Center at Northwestern Memorial Hospital and Northwestern University, Chicago. J.M.G. was supported by a Harvard Medical School Norman E. Zinberg Fellowship in Addiction Psychiatry Research. NR 61 TC 57 Z9 58 U1 9 U2 51 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 16 PY 2014 VL 34 IS 16 BP 5529 EP 5538 DI 10.1523/JNEUROSCI.4745-13.2014 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AF7WN UT WOS:000334926000014 PM 24741043 ER PT J AU Fujimoto, K Polimeni, JR van der Kouwe, AJW Reuter, M Kober, T Benner, T Fischl, B Wald, LL AF Fujimoto, Kyoko Polimeni, Jonathan R. van der Kouwe, Andre J. W. Reuter, Martin Kober, Tobias Benner, Thomas Fischl, Bruce Wald, Lawrence L. TI Quantitative comparison of cortical surface reconstructions from MP2RAGE and multi-echo MPRAGE data at 3 and 7 T SO NEUROIMAGE LA English DT Article DE Ultra high-field MRI; Quantitative morphometry; Brain segmentation; FreeSurfer; Cortical thickness ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; HUMAN BRAIN; MRI; THICKNESS; SEGMENTATION; INVERSION; CONTRAST; FIELD; COIL AB The Magnetization-Prepared 2 Rapid Acquisition Gradient Echo (MP2RAGE) method achieves spatially uniform contrast across the entire brain between gray matter and surrounding white matter tissue and cerebrospinal fluid by rapidly acquiring data at two points during an inversion recovery, and then combining the two volumes so as to cancel out sources of intensity and contrast bias, making it useful for neuroimaging studies at ultrahigh field strengths ( 7 T). To quantify the effectiveness of the MP2RAGE method for quantitative morphometric neuroimaging, we performed tissue segmentation and cerebral cortical surface reconstruction of the MP2RAGE data and compared the results with those generated from conventional multi-echo MPRAGE (MEMPRAGE) data across a group of healthy subjects. To do so, we developed a preprocessing scheme for the MP2RAGE image data to allow for automatic cortical segmentation and surface reconstruction using FreeSurfer and analysis methods to compare the positioning of the surface meshes. Using image volumes with 1 mm isotropic voxels we found a scan-rescan reproducibility of cortical thickness estimates to be 0.15 mm (or 6%) for the MEMPRAGE data and a slightly lower reproducibility of 0.19 mm (or 8%) for the MP2RAGE data. We also found that the thickness estimates were systematically smaller in the MP2RAGE data, and that both the interior and exterior cortical boundaries estimated from the MP2RAGE data were consistently positioned within the corresponding boundaries estimated from the MEMPRAGE data. Therefore several measureable differences exist in the appearance of cortical gray matter and its effect on automatic segmentation methods that must be considered when choosing an acquisition or segmentation method for studies requiring cortical surface reconstructions. We propose potential extensions to the MP2RAGE method that may help to reduce or eliminate these discrepancies. (C) 2013 Elsevier Inc. All rights reserved. C1 [Fujimoto, Kyoko; Polimeni, Jonathan R.; van der Kouwe, Andre J. W.; Reuter, Martin; Benner, Thomas; Fischl, Bruce; Wald, Lawrence L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Polimeni, Jonathan R.; van der Kouwe, Andre J. W.; Benner, Thomas; Fischl, Bruce; Wald, Lawrence L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Reuter, Martin] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kober, Tobias] EPFL SB IPSB LIFMET, Ecole Polytech Fed Lausanne, Lab Funct & Metab Imaging, CH-1015 Lausanne, Switzerland. [Kober, Tobias] Siemens Suisse SA CIBM, Adv Clin Imaging Technol, Lausanne, Switzerland. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02142 USA. RP Polimeni, JR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St Suite 2301, Charlestown, MA 02129 USA. EM jonp@nmr.mgh.harvard.edu RI Polimeni, Jonathan/P-1395-2014; Reuter, Martin/B-3456-2010; Wald, Lawrence/D-4151-2009; EPFL, Physics/O-6514-2016; OI Polimeni, Jonathan/0000-0002-1348-1179; Reuter, Martin/0000-0002-2665-9693; Fujimoto, Kyoko/0000-0002-0087-1397 FU NIH National Institute for Biomedical Imaging and Bioengineering [R01-EB006758, P41-EB015896, K01-EB011498, R01-EB006847] FX Support for this research was provided in part by the NIH National Institute for Biomedical Imaging and Bioengineering (R01-EB006758, P41-EB015896, K01-EB011498 and R01-EB006847), the National Institute on Aging (R01-AG022381, R01-AG008122), the National Center for Alternative Medicine (RC1-AT005728), the National Institute for Neurological Disorders and Stroke (R01-NS0525851, R21-N5072652, R01-NS070963), and the National Center for Research Resources (P41RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24RR021382), and was made possible by the resources provided by Shared Instrumentation Grants S10-RR023401, S10-RR019307, S10RR023043, S10-RR019371, and S10-RR020948. Additional support was provided by The Autism 82 Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (U01-MH093765), part of the multi-institutional Human Connectome Project. We thank Allison Player, Nick Schmansky, Thomas Witzel, Bastien Guerin, Dylan Tisdall, and Boris Keil for the helpful discussions. We thank an anonymous reviewer for suggesting the novel idea of a MEMPRAGE acquisition with a GRE reference. NR 50 TC 20 Z9 20 U1 1 U2 14 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 APR 15 PY 2014 VL 90 BP 60 EP 73 DI 10.1016/j.neuroimage.2013.12.012 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1TP UT WOS:000338909500007 PM 24345388 ER PT J AU Radulescu, A Mujica-Parodi, LR AF Radulescu, Anca Mujica-Parodi, Lilianne R. TI Network connectivity modulates power spectrum scale invariance SO NEUROIMAGE LA English DT Article ID HEART-RATE-VARIABILITY; ORNSTEIN-UHLENBECK PROCESS; ORBITAL PREFRONTAL CORTEX; RANDOM BRAIN NETWORKS; FUNCTIONAL MRI; TIME-SERIES; LIMBIC DYSREGULATION; NONLINEAR COMPLEXITY; NEURONAL-ACTIVITY; RATE DYNAMICS AB Measures of complexity are sensitive in detecting disease, which has made them attractive candidates for diagnostic biomarkers; one complexity measure that has shown promise in fMRI is power spectrum scale invariance (PSSI). Even if scale-free features of neuroimaging turn out to be diagnostically useful, however, their underlying neurobiological basis is poorly understood. Using modeling and simulations of a schematic prefrontal-limbic meso-circuit, with excitatory and inhibitory networks of nodes, we present here a framework for how network density within a control system can affect the complexity of signal outputs. Our model demonstrates that scale-free behavior, similar to that observed in fMRI PSSI data, can be obtained for sufficiently large networks in a context as simple as a linear stochastic system of differential equations, although the scale-free range improves when introducing more realistic, nonlinear behavior in the system. PSSI values (reflective of complexity) vary as a function of both input type (excitatory, inhibitory) and input density (mean number of long-range connections, or strength), independent of their node-specific geometric distribution. Signals show pink noise (1/j) behavior when excitatory and inhibitory influences are balanced. As excitatory inputs are increased and decreased, signals shift towards white and brown noise, respectively. As inhibitory inputs are increased and decreased, signals shift towards brown and white noise, respectively. The results hold qualitatively at the hemodynamic scale, which we modeled by introducing a neurovascular component. Comparing hemodynamic simulation results to fMRI PSSI results from 96 individuals across a wide spectrum of anxiety-levels, we show how our model can generate concrete and testable hypotheses for understanding how connectivity affects regulation of meso-circuits in the brain. (C) 2013 Elsevier Inc. All rights reserved. C1 [Radulescu, Anca] Univ Colorado, Dept Math, Boulder, CO 80309 USA. [Mujica-Parodi, Lilianne R.] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. [Mujica-Parodi, Lilianne R.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. RP Mujica-Parodi, LR (reprint author), SUNY Stony Brook, Program Neurosci, Stony Brook, NY 11794 USA. EM lilianne.strey@stonybrook.edu OI Mujica-Parodi, Lilianne/0000-0002-3752-5519 FU National Science Foundation [0954643, 1141915]; Office of Naval Research [N001404-1-005]; Burroughs Wellcome Fund [CRTG 1010138] FX This research was supported by the National Science Foundation (0954643 and 1141915; LRMP), the Office of Naval Research (N001404-1-005; LRMP) and the Burroughs Wellcome Fund (CRTG 1010138; AR). We would like to thank Aaron Clauset and Stephen Preston for our valuable discussions. NR 78 TC 6 Z9 6 U1 2 U2 7 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 APR 15 PY 2014 VL 90 BP 436 EP 448 DI 10.1016/j.neuroimage.2013.12.001 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL1TP UT WOS:000338909500043 PM 24333393 ER PT J AU Vogler, MA Smeaton, LM Wright, RL Cardoso, SW Sanchez, J Infante, R Moran, LE Godfrey, C Demeter, LM Johnson, VA AF Vogler, Mary A. Smeaton, Laura M. Wright, Rodney L. Cardoso, Sandra W. Sanchez, Jorge Infante, Rosa Moran, Laura E. Godfrey, Catherine Demeter, Lisa M. Johnson, Victoria A. TI Combination Antiretroviral Treatment for Women Previously Treated Only in Pregnancy: Week 24 Results of AIDS Clinical Trials Group Protocol A5227 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; postpartum women; efavirenz; adherence; pMTCT ID STRUCTURED TREATMENT INTERRUPTIONS; SINGLE-DOSE NEVIRAPINE; DRUG-RESISTANT HIV-1; VERTICAL TRANSMISSION; RECEIVING NEVIRAPINE; HIV-1-INFECTED WOMEN; THERAPY; ZIDOVUDINE; MUTATIONS; ADHERENCE AB Background: Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). Methods: Nonpregnant women with plasma HIV-1 RNA of >= 500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for >= 24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA < 400 copies/mL) at 24 weeks. Results: Fifty-four women were enrolled between October 2007 and December 2009; 52 of 54 completed 24 weeks of follow-up. Median baseline CD4+ T-cell count was 265/mm(3) and baseline plasma HIV-1 RNA was 4.6 log(10) copies per milliliter. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42 of 52 women or 81% (exact 95% confidence interval: 68% to 90%). There were no differences in response by country, by number, or class of prior pMTCT exposures. Although confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. Conclusions: In this first prospective clinical trial studying combination antiretroviral retreatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported nonadherence. C1 [Vogler, Mary A.] Cornell Univ, Weill Cornell Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. [Smeaton, Laura M.] Harvard Univ, Sch Publ Hlth, Ctr Biostat & AIDS Res, Boston, MA 02115 USA. [Wright, Rodney L.] Albert Einstein Coll Med, Dept Obstet & Gynecol, Bronx, NY 10467 USA. [Cardoso, Sandra W.] Fundacao Oswaldo Cruz, Inst Pesquisa Clin Evandro Chagas, STD AIDS Clin Res Lab, Rio De Janeiro, Brazil. [Sanchez, Jorge; Infante, Rosa] Asociac Civil IMPACTA Salud & Educ, Lima, Peru. [Moran, Laura E.] Social & Sci Syst Inc, Silver Spring, MD USA. [Godfrey, Catherine] NIAID, HIV Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA. [Demeter, Lisa M.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Johnson, Victoria A.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. RP Vogler, MA (reprint author), Cornell Univ, Weill Cornell Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. EM mav9046@med.cornell.edu FU National Institute of Allergy and Infectious Diseases [U01AI068636]; National Institute of Mental Health, National Institute of Dental and Craniofacial Research; Statistical and Data Management Center of the AIDS Clinical Trials Group under the National Institute of Allergy and Infectious Diseases [1 U01AI068634]; University of Alabama at Birmingham ACTG CTU grant [U01 AI069918]; Instituto de Pesquisa Clinica Evandro Chagas CRS Fiocruz Therapeutic and Prevention HIV AIDS CTU grant [12101, 1 U01 AI069476-01]; IMPACTA Peru CTU grant [1U01AI069438-01]; Weill Cornell Medical College ACTG CTU grant [5U01AI069419]; University of Rochester CTU grant [1U01 AI069511] FX Supported by Award no. U01AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health, National Institute of Dental and Craniofacial Research. 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. Supported by the Statistical and Data Management Center of the AIDS Clinical Trials Group under the National Institute of Allergy and Infectious Diseases grant no. 1 U01AI068634. UAB Virology Specialty Laboratory 54 support VSL UM1 AI068636 and UAB CFAR P30; AI27767 for laboratory support and core research facilities within UAB Center for AIDS Research/University of Alabama at Birmingham School of Medicine and Birmingham Veterans Affairs Medical Center, Birmingham Alabama; University of Alabama at Birmingham ACTG CTU grant no. U01 AI069918; Instituto de Pesquisa Clinica Evandro Chagas CRS (12101) Fiocruz Therapeutic and Prevention HIV AIDS CTU grant no. 1 U01 AI069476-01; IMPACTA Peru CTU grant no. 1U01AI069438-01; Weill Cornell Medical College ACTG CTU grant no. 5U01AI069419; University of Rochester CTU grant no. 1U01 AI069511; Bristol Myers Squibb Company, Gilead Sciences, Inc, and Merck & Co, Inc, provided study drugs. NR 31 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2014 VL 65 IS 5 BP 542 EP 550 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4XX UT WOS:000337684400009 PM 24759064 ER PT J AU Yoon, C Davis, JL Huang, L Muzoora, C Byakwaga, H Scibetta, C Bangsberg, DR Nahid, P Semitala, FC Hunt, PW Martin, JN Cattamanchi, A AF Yoon, Christina Davis, J. Lucian Huang, Laurence Muzoora, Conrad Byakwaga, Helen Scibetta, Colin Bangsberg, David R. Nahid, Payam Semitala, Fred C. Hunt, Peter W. Martin, Jeffrey N. Cattamanchi, Adithya TI Point-of-Care C-Reactive Protein Testing to Facilitate Implementation of Isoniazid Preventive Therapy for People Living With HIV SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE tuberculosis; HIV; isoniazid preventive therapy; WHO symptom screen; C-reactive protein; TB screening ID ANTIRETROVIRAL THERAPY; PULMONARY TUBERCULOSIS; PROGNOSTIC VALUE; FOOD INSECURITY; PROCALCITONIN; PNEUMONIA; RECLASSIFICATION; INDIVIDUALS AB Background: Symptom-based tuberculosis screening identifies less than one-third of eligible HIV-infected patients as candidates for isoniazid preventive therapy (IPT). We evaluated whether testing for C-reactive protein (CRP) improves patient selection for IPT. Methods: We measured CRP levels (normal <10 mg/L) using a point-of-care (POC) assay on stored serum samples from HIV-infected Ugandan adults initiating antiretroviral therapy. We assessed diagnostic accuracy in reference to baseline tuberculosis status adjudicated by an expert committee and calculated net reclassification improvement to quantify the incremental discriminatory benefit of POC-CRP in determining IPT eligibility compared to the World Health Organization (WHO) symptom screen. Results: Of 201 patients (median CD4 cell count, 137 cells/mL; interquartile range, 83-206), 5 (2.5%) had tuberculosis. Compared to the WHO symptom screen, POC-CRP had similar sensitivity (100% vs. 80%, P = 0.30) but greater specificity (21% vs. 87%, P < 0.0001) for tuberculosis. If based on the WHO symptom screen, no patients with tuberculosis but only 42 of 196 patients without tuberculosis would have been considered IPT eligible. If POC-CRP were used instead, 1 patient with tuberculosis (reclassification of cases, -20%; P = 0.32) and 129 patients without tuberculosis (reclassification of noncases, +66%; P < 0.001) would have been reclassified as IPT eligible, a net reclassification improvement of 46% (P = 0.03). In addition, POC-CRP testing would have reduced the proportion of patients without active tuberculosis requiring confirmatory tuberculosis testing (87% vs. 21%, P < 0.0001). Conclusions: POC-CRP testing increased more than 4-fold the proportion of HIV-infected adults immediately identified as IPT eligible and decreased the proportion of patients requiring referral for further tuberculosis diagnostic testing. POC-CRP testing could substantially improve implementation of tuberculosis screening guidelines. C1 [Yoon, Christina; Davis, J. Lucian; Huang, Laurence; Nahid, Payam; Cattamanchi, Adithya] Univ Calif San Francisco, San Francisco Gen Hosp, Div Pulm & Crit Care Med, Dept Med, San Francisco, CA USA. [Davis, J. Lucian; Cattamanchi, Adithya] Univ Calif San Francisco, San Francisco Gen Hosp, Curry Int TB Ctr, San Francisco, CA USA. [Huang, Laurence; Hunt, Peter W.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, Dept Med, San Francisco, CA USA. [Muzoora, Conrad; Byakwaga, Helen; Bangsberg, David R.] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda. [Byakwaga, Helen; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Scibetta, Colin] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA. [Bangsberg, David R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Semitala, Fred C.] Makerere Univ, Dept Med, Kampala, Uganda. RP Yoon, C (reprint author), San Francisco Gen Hosp, Div Pulm & Crit Care Med, Room 5K1,1001 Potrero Ave, San Francisco, CA 94110 USA. EM christina.yoon@ucsf.edu FU National Institutes of Health; University of California San Francisco; Gladstone Institute of Virology and Immunology Center for AIDS Research [P30 AI027763]; National Heart, Lung and Blood Institutes at the National Institutes of Health [T32 HL007185] FX This research was supported by a grant from the National Institutes of Health, University of California San Francisco, Gladstone Institute of Virology and Immunology Center for AIDS Research (P30 AI027763 to C.Y.) and the National Heart, Lung and Blood Institutes at the National Institutes of Health [T32 HL007185 to C.Y.]. The iCHROMA POC-CRP Reader and POC-CRP assays used in this study were donated by the manufacturer, BodiTech Med Inc., South Korea. Neither the funders nor BodiTech Med Inc., had any role in study design, data collection/analysis, decision to publish, or preparation of the manuscript. NR 27 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2014 VL 65 IS 5 BP 551 EP 556 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4XX UT WOS:000337684400010 PM 24346636 ER PT J AU Campo, M Oursler, KK Huang, L Goetz, MB Rimland, D Hoo, GS Brown, ST Rodriguez-Barradas, MC Au, D Akgun, KM Shahrir, S Crothers, K AF Campo, Monica Oursler, Krisann K. Huang, Laurence Goetz, Matthew Bidwell Rimland, David Hoo, Guy Soo Brown, Sheldon T. Rodriguez-Barradas, Maria C. Au, David Akguen, Kathleen M. Shahrir, Shahida Crothers, Kristina TI Association of Chronic Cough and Pulmonary Function With 6-Minute Walk Test Performance in HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE 6-MWT; HIV; airflow limitation; performance; pulmonary function tests; FEV1 ID HUMAN-IMMUNODEFICIENCY-VIRUS; VETERANS AGING COHORT; PEAK OXYGEN-UPTAKE; ANTIRETROVIRAL THERAPY; RESPIRATORY SYMPTOMS; REFERENCE EQUATIONS; DIFFUSING-CAPACITY; DISTANCE; ADULTS; LUNG AB Objective: Chronic lung disease has been associated with greater impairment in self-reported physical function in HIV-infected patients. We sought to study this association using objective measures of physical function and pulmonary function. Design: Baseline data from the Examinations of HIV Associated Lung Emphysema study, a multicenter observational cohort of HIV-infected and uninfected veterans. Methods: We assessed the association between clinical, laboratory, and pulmonary function measures with 6-minute walk test (6-MWT). Multivariable linear regression models were generated to identify factors associated with 6-MWT performance. Results: Three hundred forty participants completed 6-MWT (mean age 55 years), with 68% blacks, 94% men, and 62% current smokers. Overall, 180 (53%) were HIV-infected and 63 (19%) had spirometry-defined chronic obstructive pulmonary disease. In a multivariable model, age, current smoking, and obesity (body mass index. 30) were independently associated with lower 6-MWT performance, but HIV infection was not; there was a significant interaction between HIV and chronic cough, such that distance walked among HIV-infected participants with chronic cough was 51.76 m less (P = 0.04) compared with those without cough or HIV. Among HIV-infected participants, the forced expiratory volume in 1 second (FEV1, percent predicted), to a greater extent than total lung capacity or diffusing capacity, attenuated the association with chronic cough; decreased FEV1 was independently associated with lower 6-MWT performance in those with HIV. Conclusions: Older age, current smoking, and airflow limitation were important determinants of 6-MWT performance in the HIV-infected participants. These findings suggest that potential interventions to improve physical function may include early management of respiratory symptoms and airflow limitation. C1 [Campo, Monica; Au, David; Shahrir, Shahida; Crothers, Kristina] Univ Washington, Dept Pulm & Crit Care Med, Seattle, WA 98104 USA. [Oursler, Krisann K.] Baltimore Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Oursler, Krisann K.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Huang, Laurence] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Huang, Laurence] Univ Calif San Francisco, Dept Med, Div HIV AIDS, San Francisco, CA USA. [Goetz, Matthew Bidwell] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Infect Dis Sect, Dept Med, Los Angeles, CA 90095 USA. [Rimland, David] Atlanta Vet Affairs Med Ctr, Div Infect Dis, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Hoo, Guy Soo] Vet Affairs Greater Los Angeles Healthcare Syst, West Los Angeles Healthcare Ctr, Pulm & Crit Care Sect, Los Angeles, CA USA. [Brown, Sheldon T.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Brown, Sheldon T.] Icahn Sch Med Mt Sinai, Dept Med & Infect Dis, Bronx, NY USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VAMC, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Akguen, Kathleen M.] Vet Affairs Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT USA. [Akguen, Kathleen M.] Yale Univ, Sch Med, New Haven, CT USA. RP Campo, M (reprint author), Univ Washington, Harborview Med Ctr, Dept Pulm & Crit Care Med, 325 9th Ave Box 359762, Seattle, WA 98104 USA. EM mcampo@u.washington.edu OI Goetz, Matthew/0000-0003-4542-992X; Crothers, Kristina/0000-0001-9702-0371 FU National Institutes of Health (NIH) [HL090342]; Firland Foundation; Department of Veterans Affairs (VA), Health Services Research and Development; Department of Veterans Affairs; Veterans Health Administration, VISN 1 Career Development Award; Association of Subspecialty Physicians; CHEST Foundation of the American College of Chest Physicians; [NIH R01 HL095136]; [K23 AG02489]; [NIH HL 087713] FX Supported in part by a grant from the National Institutes of Health (NIH) HL090342 (to K.C.); M.C. was supported by the Firland Foundation. K.A.O. was supported by grant NIH R01 HL095136 and K23 AG02489. L. H. was supported by grant NIH HL 087713. Dr D. A. was supported through the Department of Veterans Affairs (VA), Health Services Research and Development. KMA was supported by the Department of Veterans Affairs, Veterans Health Administration, VISN 1 Career Development Award and the Association of Subspecialty Physicians and the CHEST Foundation of the American College of Chest Physicians. NR 38 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2014 VL 65 IS 5 BP 557 EP 563 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4XX UT WOS:000337684400011 PM 24346638 ER PT J AU Hoffmann, A Stoffel, MH Nitzsche, B Lobsien, D Seeger, J Schneider, H Boltze, J AF Hoffmann, Anke Stoffel, Michael H. Nitzsche, Bjoern Lobsien, Donald Seeger, Johannes Schneider, Holm Boltze, Johannes TI The Ovine Cerebral Venous System: Comparative Anatomy, Visualization, and Implications for Translational Research SO PLOS ONE LA English DT Article ID SUPERIOR SAGITTAL SINUS; LARGE ANIMAL-MODEL; ONTOGENIC DEVELOPMENT; CHORDAE WILLISII; CAVERNOUS SINUS; SHEEP; ISCHEMIA; DRAINAGE; CATHETERIZATION; PATTERN AB Cerebrovascular diseases are significant causes of death and disability in humans. Improvements in diagnostic and therapeutic approaches strongly rely on adequate gyrencephalic, large animal models being demanded for translational research. Ovine stroke models may represent a promising approach but are currently limited by insufficient knowledge regarding the venous system of the cerebral angioarchitecture. The present study was intended to provide a comprehensive anatomical analysis of the intracranial venous system in sheep as a reliable basis for the interpretation of experimental results in such ovine models. We used corrosion casts as well as contrast-enhanced magnetic resonance venography to scrutinize blood drainage from the brain. This combined approach yielded detailed and, to some extent, novel findings. In particular, we provide evidence for chordae Willisii and lateral venous lacunae, and report on connections between the dorsal and ventral sinuses in this species. For the first time, we also describe venous confluences in the deep cerebral venous system and an 'anterior condylar confluent' as seen in humans. This report provides a detailed reference for the interpretation of venous diagnostic imaging findings in sheep, including an assessment of structure detectability by in vivo (imaging) versus ex vivo (corrosion cast) visualization methods. Moreover, it features a comprehensive interspecies-comparison of the venous cerebral angioarchitecture in man, rodents, canines and sheep as a relevant large animal model species, and describes possible implications for translational cerebrovascular research. C1 [Hoffmann, Anke; Seeger, Johannes] Univ Leipzig, Inst Anat Histol & Embryol, Fac Vet Med, D-04109 Leipzig, Germany. [Stoffel, Michael H.] Univ Bern, Vetsuisse Fac, Div Vet Anat, Bern, Switzerland. [Nitzsche, Bjoern; Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, Dept Cell Therapy, Leipzig, Germany. [Lobsien, Donald] Univ Hosp Leipzig, Dept Neuroradiol, Leipzig, Germany. [Schneider, Holm] Univ Hosp Erlangen, Dept Pediat, Erlangen, Germany. [Boltze, Johannes] Univ Leipzig, Translat Ctr Regenerat Med, D-04109 Leipzig, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Charlestown, MA USA. [Boltze, Johannes] Harvard Univ, Sch Med, Neurovasc Regulat Lab, Neurosci Ctr, Charlestown, MA USA. RP Boltze, J (reprint author), Fraunhofer Inst Cell Therapy & Immunol, Dept Cell Therapy, Leipzig, Germany. EM johannes.boltze@izi.fraunhofer.de RI Stoffel, Michael/I-6939-2015; OI Stoffel, Michael/0000-0002-4699-5125; Nitzsche, Bjorn/0000-0002-4759-0760 FU University of Leipzig; Fraunhofer-Institute of Cell Therapy and Immunology FX This project was financed by intramural funds and resources provided by the University of Leipzig and the Fraunhofer-Institute of Cell Therapy and Immunology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 6 Z9 6 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 15 PY 2014 VL 9 IS 4 AR e92990 DI 10.1371/journal.pone.0092990 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5PW UT WOS:000336922600012 PM 24736654 ER PT J AU Patel, SR Ghose, K Eskandar, EN AF Patel, Shaun R. Ghose, Kaushik Eskandar, Emad N. TI An Open Source 3-D Printed Modular Micro-Drive System for Acute Neurophysiology SO PLOS ONE LA English DT Article ID NONHUMAN-PRIMATES; MACAQUE MONKEYS; ARRAY; RECORDINGS; CHAMBER; REGIONS AB Current, commercial, electrode micro-drives that allow independent positioning of multiple electrodes are expensive. Custom designed solutions developed by individual laboratories require fabrication by experienced machinists working in well equipped machine shops and are therefore difficult to disseminate into widespread use. Here, we present an easy to assemble modular micro-drive system for acute primate neurophysiology (PriED) that utilizes rapid prototyping (3-d printing) and readily available off the shelf-parts. The use of 3-d printed parts drastically reduces the cost of the device, making it available to labs without the resources of sophisticated machine shops. The direct transfer of designs from electronic files to physical parts also gives researchers opportunities to easily modify and implement custom solutions to specific recording needs. We also demonstrate a novel model of data sharing for the scientific community: a publicly available repository of drive designs. Researchers can download the drive part designs from the repository, print, assemble and then use the drives. Importantly, users can upload their modified designs with annotations making them easily available for others to use. C1 [Patel, Shaun R.; Ghose, Kaushik; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Nayef Al Rodhan Labs, Boston, MA 02114 USA. [Patel, Shaun R.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Patel, SR (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Nayef Al Rodhan Labs, Boston, MA 02114 USA. EM shaun.patel@me.com FU National Institutes of Health NIDA [R01DA026297]; NEI [1R01EY017658-01A1]; NIMH Conte Award [MH086400]; Klingenstein Foundation; Howard Hughes Medical Institute; Dana Foundation; Sackler Programme in Psychobiology FX This work was supported by grants from the National Institutes of Health NIDA R01DA026297. ENE was supported by NEI 1R01EY017658-01A1, NIMH Conte Award MH086400, the Klingenstein Foundation, Howard Hughes Medical Institute, and Dana Foundation. SRP was supported by the Sackler Programme in Psychobiology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 16 TC 0 Z9 0 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 15 PY 2014 VL 9 IS 4 AR e94262 DI 10.1371/journal.pone.0094262 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5PW UT WOS:000336922600054 PM 24736691 ER PT J AU Toschi, L Finocchiaro, G Nguyen, TT Skokan, MC Giordano, L Gianoncelli, L Perrino, M Siracusano, L Di Tommaso, L Infante, M Alloisio, M Roncalli, M Scorsetti, M Janne, PA Santoro, A Varella-Garcia, M AF Toschi, Luca Finocchiaro, Giovanna Nguyen, Teresa T. Skokan, Margaret C. Giordano, Laura Gianoncelli, Letizia Perrino, Matteo Siracusano, Licia Di Tommaso, Luca Infante, Maurizio Alloisio, Marco Roncalli, Massimo Scorsetti, Marta Jaenne, Pasi A. Santoro, Armando Varella-Garcia, Marileila TI Increased SOX2 Gene Copy Number Is Associated with FGFR1 and PIK3CA Gene Gain in Non-Small Cell Lung Cancer and Predicts Improved Survival in Early Stage Disease SO PLOS ONE LA English DT Article ID OPEN-LABEL; AMPLIFICATION; CARCINOMAS; GROWTH; TRANSCRIPTION; SENSITIVITY; ONCOGENE; 1ST-LINE; MUTATION; PATHWAY AB Background: We aimed to investigate prevalence and prognostic role of SOX2, PIK3CA, FGFR1 and BRF2 gene gain in patients with surgically resected non-small cell lung cancer (NSCLC). Methods: SOX2, PIK3CA, FGFR1 and BRF2 gene copy number was assessed by fluorescence in situ hybridization (FISH) in arrayed tissue cores from 447 resected NSCLCs. Results: Increased gene copy number (FISH+) for SOX2, PIK3CA, FGFR1 and BRF2 was observed in 23.6%, 29.2%, 16.6% and 14.9% of cases, respectively. FISH+ status for each gene was significantly associated with smoking history, squamous cell carcinoma (SCC) histology, and increased copy number of the other studied genes. Multivariate analysis of overall survival indicated increased SOX2 gene copy number (P = 0.008), stage I-II (P<0.001), and adenocarcinoma or SCC histology (P = 0.016) as independent, favorable prognostic factors. A statistically significant interaction was observed between stage and SOX2 gene status (P = 0.021), indicating that the prognostic impact of SOX2 gene gain differs across stages and is limited to patients with stage I-II disease (HR 0.44, 95% CI: 0.25-0.77; P = 0.004, adjusted for histology). Conclusions: Increased SOX2 gene copy number is an independent and favorable prognostic factor in surgically resected, early stage NSCLC, regardless of histology. SOX2, PIK3CA, FGFR1 and BRF2 gene gains are likely to occur concurrently, with potentially relevant implications for the development of new therapeutic strategies. C1 [Toschi, Luca; Finocchiaro, Giovanna; Gianoncelli, Letizia; Perrino, Matteo; Siracusano, Licia; Santoro, Armando] Humanitas Clin & Res Ctr, Div Hematol & Oncol, Milan, Italy. [Nguyen, Teresa T.; Varella-Garcia, Marileila] Univ Colorado, Sch Med, Aurora, CO USA. [Skokan, Margaret C.] Denver Police Dept Crime Lab, Forens Biol DNA, Denver, CO USA. [Giordano, Laura] Humanitas Clin & Res Ctr, Biostat Unit, Milan, Italy. [Di Tommaso, Luca; Roncalli, Massimo] Humanitas Clin & Res Ctr, Div Pathol, Milan, Italy. [Di Tommaso, Luca; Roncalli, Massimo] Univ Milan, Milan, Italy. [Infante, Maurizio; Alloisio, Marco] Humanitas Clin & Res Ctr, Div Thorac Surg, Milan, Italy. [Scorsetti, Marta] Humanitas Clin & Res Ctr, Dept Radiotherapy, Milan, Italy. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. RP Toschi, L (reprint author), Humanitas Clin & Res Ctr, Div Hematol & Oncol, Milan, Italy. EM luca.toschi@cancercenter.humanitas.it OI Scorsetti, Marta/0000-0003-0320-559X FU Colorado Lung Cancer SPORE NCI [P50CA058187]; NCI CCSG [P30CA046934]; NIH/NCATS Colorado CTSI [KL2TR000156] FX This work was supported by private donation from Mr. Gerry Scotti, Colorado Lung Cancer SPORE NCI P50CA058187, NCI CCSG P30CA046934 and NIH/NCATS Colorado CTSI KL2TR000156 grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 18 Z9 19 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 15 PY 2014 VL 9 IS 4 AR e95303 DI 10.1371/journal.pone.0095303 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5PW UT WOS:000336922600167 PM 24736592 ER PT J AU Batchelor, TT AF Batchelor, Tracy T. TI Comment: Defining cure in primary CNS lymphoma SO NEUROLOGY LA English DT Editorial Material AB Primary CNS lymphoma (PCNSL), a type of extranodal non-Hodgkin lymphoma, is a potentially curable brain cancer. Ongoing randomized trials assessing treatments for PCNSL will ultimately establish a standard of care. Until that time, practitioners have multiple treatment options from which to choose. In this report, the authors provide long-term follow-up data from a phase 2 clinical trial in newly diagnosed PCNSL patients, ages 18-70, treated with MATILDE chemotherapy followed by whole-brain radiation therapy (WBRT).(1) The MATILDE regimen, like all induction chemotherapy currently utilized for PCNSL, includes methotrexate, the single most effective agent against PCNSL. Following chemotherapy, patients received a consolidative WBRT dose based on their initial response to chemotherapy. C1 [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Div Hematol Oncol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Hematol Oncol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Boston, MA USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Hematol Oncol, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR 15 PY 2014 VL 82 IS 15 BP 1373 EP 1373 DI 10.1212/WNL.0000000000000323 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AH9XG UT WOS:000336498000019 PM 24634452 ER PT J AU Spring, B Sohn, MW Locatelli, SM Hadi, S Kahwati, L Weaver, FM AF Spring, Bonnie Sohn, Min-Woong Locatelli, Sara M. Hadi, Sattar Kahwati, Leila Weaver, Frances M. TI Individual, facility, and program factors affecting retention in a national weight management program SO BMC PUBLIC HEALTH LA English DT Article DE Overweight; Obesity; Veterans; Veterans health; Health education; Weight loss ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE; VETERANS; INTERNET; TECHNOLOGY; PREDICTORS; ATTRITION; OBESITY; ADULTS AB Background: High attrition is a common problem for weight loss programs and directly affects program effectiveness. Since 2006, the Veterans Health Administration (VHA) has offered obesity treatment to its beneficiaries through the MOVE! Weight Management Program for Veterans (MOVE!). An early evaluation of this program showed that attrition rate was high. The present study examines how individual, facility, and program factors relate to retention for participants in the on-site MOVE! group program. Methods: Data for all visits to MOVE! group treatment sessions were extracted from the VHA outpatient database. Participants were classified into three groups by their frequency of visits to the group program during a six month period after enrollment: early dropouts (1 - 3 visits), late dropouts (4 - 5 visits), and completers (6 or more visits). A generalized ordered logit model was used to examine individual, facility, and program factors associated with retention. Results: More than 60% of participants were early dropouts and 11% were late dropouts. Factors associated with retention were older age, presence of one or more comorbidities, higher body mass index at baseline, lack of co-payment requirement, geographic proximity to VA facility, addition of individual consultation to group treatment, greater program staffing, and regular, on-site physical activity programming. A non-completion rate of 74% for on-site group obesity treatment poses a major challenge to reducing the population prevalence of obesity within the VHA. Conclusions: Greater attention to individualized consultation, accessibility to the program, and facility factors including staffing and physical activity resources may improve retention. C1 [Spring, Bonnie] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Sohn, Min-Woong; Locatelli, Sara M.; Weaver, Frances M.] Edward Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Sohn, Min-Woong] Northwestern Univ, Ctr Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Hadi, Sattar] Edward Hines Jr VA Hosp, Patient Care Serv, Hines, IL 60141 USA. [Kahwati, Leila] US Dept Vet Affairs, Natl Ctr Hlth Promot & Dis Prevent, Off Patient Care Serv, Vet Hlth Adm, Durham, NC USA. [Weaver, Frances M.] Loyola Univ Chicago, Stritch Sch Med, Hlth Serv Res Program, Maywood, IL USA. RP Sohn, MW (reprint author), Edward Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. EM msohn@northwestern.edu RI Sohn, Min-Woong/C-3560-2015 OI Sohn, Min-Woong/0000-0002-9474-2907 FU US Department of Veterans Affairs Health Services Research and Development Service [PPO 10-100-1]; National Institutes of Health [RC1DK087126, R01 HL075451] FX The authors gratefully acknowledge the financial support of the US Department of Veterans Affairs Health Services Research and Development Service (PPO 10-100-1; Min-Woong Sohn, Ph.D., Principal Investigator) and the National Institutes of Health (RC1DK087126 and R01 HL075451; Bonnie Spring, Ph.D., Principal Investigator). The paper presents the findings and conclusions of the authors; it does not necessarily represent the Department of Veterans Affairs or Health Services Research and Development Service nor the NIH. The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 30 TC 3 Z9 3 U1 2 U2 11 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 APR 15 PY 2014 VL 14 AR 363 DI 10.1186/1471-2458-14-363 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH5NO UT WOS:000336177200001 PM 24735508 ER PT J AU Kunadian, V Giugliano, RP Newby, LK Zorkun, C Guo, JP Bagai, A Montalescot, G Braunwald, E Califf, RM Van de Werf, F Armstrong, PW Harrington, R Gibson, CM AF Kunadian, Vijay Giugliano, Robert P. Newby, L. Kristin Zorkun, Cafer Guo, Jianping Bagai, Akshay Montalescot, Gilles Braunwald, Eugene Califf, Robert M. Van de Werf, Frans Armstrong, Paul W. Harrington, Robert Gibson, C. Michael TI Angiographic Outcomes With Early Eptifibatide Therapy in Non-ST-Segment Elevation Acute Coronary Syndrome (from the EARLY ACS Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLYCOPROTEIN IIB/IIIA INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; FRAME COUNT; INTERVENTION; METAANALYSIS; ANGIOPLASTY; CLOPIDOGREL; EVENTS; FLOW AB Early administration of glycoprotein IIbIIIa inhibitors results in improved angiographic parameters, including thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count, and TIMI myocardial perfusion grade (TMPG) among patients with ST-segment elevation myocardial infarction. Whether the same is true in the setting of non ST-segment elevation acute coronary syndrome is unknown. The goal of the early glycoprotein IIbIIIa inhibition in non ST-segment elevation acute coronary syndrome (EARLY ACS) angiographic substudy was to compare angiographic outcomes among patients with non ST-segment elevation acute coronary syndrome who were administered early routine versus delayed provisional eptifibatide. Of 9,406 patients in the EARLY ACS trial, 2,066 patients were included in the angiographic substudy (early routine eptifibatide [n = 1,042] or early placebo [n = 1,024] with delayed provisional eptifibatide after angiography and before percutaneous coronary intervention [PCI]). The angiographic substudy primary end point was the incidence of TMPG 3 before and after PCI. TMPG 3 before (43.7% vs 44.9%, p = 0.58) and after PCI (52.4% vs 50.1%, p = 0.73) was similar for early routine versus delayed provisional eptifibatide, respectively. Angiographic procedural complications consisting of a composite of loss of side branch, abrupt vessel closure, distal embolization, and no reflow occurred less frequently in early routine group versus delayed provisional group (9.3% vs 13.6%, respectively, p = 0.01). In the EARLY ACS angiographic substudy, the use of early routine eptifibatide resulted in fewer angiographic procedural complications. These data provide support for the use of eptifibatide in the catheterization laboratory during high-risk cases merely to prevent angiographic procedural complications. (c) 2014 Elsevier Inc. All rights reserved. C1 [Kunadian, Vijay] Newcastle Univ, Fac Med Sci, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England. [Kunadian, Vijay] Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Ctr Cardiothorac, Newcastle Upon Tyne, Tyne & Wear, England. [Giugliano, Robert P.; Guo, Jianping; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Newby, L. Kristin; Bagai, Akshay; Califf, Robert M.] Duke Clin Res Inst, Durham, NC USA. [Zorkun, Cafer] Yedikule Educ & Res Hosp Istanbul, Istanbul, Turkey. [Montalescot, Gilles] Hop La Pitie Salpetriere, Dept Cardiol, Paris, France. [Van de Werf, Frans] Univ Hosp Leuven, Dept Cardiovasc Med, Leuven, Belgium. [Armstrong, Paul W.] Univ Alberta, Dept Med, Edmonton, AB T6G 2M7, Canada. [Harrington, Robert] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Gibson, C. Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, PERFUSE Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02215 USA. RP Gibson, CM (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, PERFUSE Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02215 USA. EM mgibson@perfuse.org OI Van de Werf, Frans/0000-0001-9479-7767 FU Schering-Plough; Millennium Pharmaceuticals (New Jersey) FX The EARLY ACS trial was supported by Schering-Plough and Millennium Pharmaceuticals (New Jersey). NR 20 TC 3 Z9 3 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2014 VL 113 IS 8 BP 1297 EP 1305 DI 10.1016/j.amjcard.2014.01.404 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AF3YG UT WOS:000334648000006 PM 24607027 ER PT J AU Buchanan, GL Chieffo, A Meliga, E Mehran, R Park, SJ Onuma, Y Capranzano, P Valgimigli, M Narbute, I Makkar, RR Palacios, IF Kim, YH Buszman, PP Chakravarty, T Sheiban, I Naber, C Margey, R Agnihotri, A Marra, S Capodanno, D Allgar, V Leon, MB Moses, JW Fajadet, J Lefevre, T Morice, MC Erglis, A Tamburino, C Alfieri, O Serruys, PW Colombo, A AF Buchanan, Gill Louise Chieffo, Alaide Meliga, Emanuele Mehran, Roxana Park, Seung-Jung Onuma, Yoshinobu Capranzano, Piera Valgimigli, Marco Narbute, Inga Makkar, Raj R. Palacios, Igor F. Kim, Young-Hak Buszman, Piotr P. Chakravarty, Tarun Sheiban, Imad Naber, Christoph Margey, Ronan Agnihotri, Arvind Marra, Sebastiano Capodanno, Davide Allgar, Victoria Leon, Martin B. Moses, Jeffrey W. Fajadet, Jean Lefevre, Thierry Morice, Marie-Claude Erglis, Andrejs Tamburino, Corrado Alfieri, Ottavio Serruys, Patrick W. Colombo, Antonio TI Comparison of Percutaneous Coronary Intervention (With Drug-Eluting Stents) Versus Coronary Artery Bypass Grafting in Women With Severe Narrowing of the Left Main Coronary Artery (from the Women-Drug-Eluting stent for LefT main coronary Artery disease Registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID UNPROTECTED LEFT MAIN; IN-HOSPITAL MORTALITY; SURGICAL REVASCULARIZATION; SEX-DIFFERENCES; SURGERY; ANGIOPLASTY; IMPLANTATION; STENOSIS; OUTCOMES; TRIAL AB Women typically present with coronary artery disease later than men with more unfavorable clinical and anatomic characteristics. It is unknown whether differences exist in women undergoing treatment for unprotected left main coronary artery (ULMCA) disease. Our aim was to evaluate long-term clinical outcomes in women treated with percutaneous coronary intervention (PCI) with drug-eluting stents versus coronary artery bypass grafting (CABG). All consecutive women from the Drug-Eluting stent for LefT main coronary Artery disease registry with ULMCA disease were analyzed. A propensity matching was performed to adjust for baseline differences. In total, 817 women were included: 489 (59.8%) underwent treatment with PCI with drug-eluting stents versus 328 (40.2%) with CABG. Propensity score matching identified 175 matched pairs, and at long-term follow-up there were no differences in all-cause (odds ratio [OR] 0.722, 95% confidence interval [CI] 0.357 to 1.461, p = 0.365) or cardiovascular (OR 1.100, 95% CI 0.455 to 2.660, p = 0.832) mortality, myocardial infarction (MI; OR 0.362, 95% CI 0.094 to 1.388, p = 0.138), or cerebrovascular accident (CVA; OR 1.200, 95% CI 0.359 to 4.007, p = 0.767) resulting in no difference in the primary study objective of death, MI, or CVA (OR 0.711, 95% CI 0.387 to 1.308, p = 0.273). However, there was an advantage of CABG in major adverse cardiovascular and cerebrovascular events (OR 0.429, 95% CI 0.254 to 0.723, p = 0.001), driven exclusively by target vessel revascularization (OR 0.185, 95% CI 0.079 to 0.432, p <0.001). In women with significant ULMCA disease, no difference was observed after PCI or CABG in death, MI, and CVA at long-term follow-up. (C) 2014 Elsevier Inc. All rights reserved. C1 [Buchanan, Gill Louise; Chieffo, Alaide; Alfieri, Ottavio; Colombo, Antonio] Ist Sci San Raffaele, I-20132 Milan, Italy. [Meliga, Emanuele] AO Ordine Mauriziano Umberto I, Turin, Italy. [Mehran, Roxana] Mt Sinai Med Ctr, New York, NY 10029 USA. [Park, Seung-Jung; Kim, Young-Hak] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Onuma, Yoshinobu; Serruys, Patrick W.] Erasmus MC, Thoraxctr, Rotterdam, Netherlands. [Capranzano, Piera; Capodanno, Davide; Tamburino, Corrado] Univ Catania, Ferrarotto Hosp, Catania, Italy. [Valgimigli, Marco] Univ Ferrara, S Anna Hosp, I-44100 Ferrara, Italy. [Narbute, Inga; Erglis, Andrejs] Pauls Stradins Clin Univ Hosp, Riga, Latvia. [Narbute, Inga; Erglis, Andrejs] Univ Latvia, Riga, Latvia. [Makkar, Raj R.; Chakravarty, Tarun] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Harvard Univ, Sch Med, Boston, MA USA. [Buszman, Piotr P.] Amer Heart Poland Inc, Katowice, Poland. [Sheiban, Imad; Marra, Sebastiano] Univ Turin, S Giovanni Battista Molinette Hosp, Turin, Italy. [Naber, Christoph] Elisabeth Hosp, Contilia Heart & Vasc Ctr, Essen, Germany. [Allgar, Victoria] Univ York, York YO10 5DD, N Yorkshire, England. [Leon, Martin B.; Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York, NY USA. [Leon, Martin B.; Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA. [Fajadet, Jean] Clin Pasteur, Toulouse, France. [Lefevre, Thierry; Morice, Marie-Claude] Hop Prive Jacques Cartier, Massy, France. RP Chieffo, A (reprint author), Ist Sci San Raffaele, I-20132 Milan, Italy. EM chieffo.alaide@hsr.it FU BMS/Sanofi (Bridgewater, New Jersey); Medicines Company; Lilly/Daiichi Sankyo (Chuo-ko, Tokyo, Japan); Eli Lilly and Medtronic; Abbott; Biotronik; Sadra Medical (Campbell, California); Stentys; Icon (Dublin, Ireland) FX Dr. Mehran is a consultant to Abbott (Abbott Park, Illinois), The Medicines Company (Parsippany, New Jersey), Janssen (Titusville, New Jersey), and Regado (Durham, North Carolina) and has received research grant support from BMS/Sanofi (Bridgewater, New Jersey), The Medicines Company, and Lilly/Daiichi Sankyo (Chuo-ko, Tokyo, Japan). Dr. Makkar is a consultant to Medtronic (Minneapolis, Minnesota) and Abiomed (Danvers, Massachusetts), has received speaker's fees from Eli Lilly and Medtronic, and has received equity from Entourage Medical Technologies (Menlo Park, California). Dr. Naber is a speaker for Abbott, Cordis (East Bridgewater, New Jersey), Biotronik (Lake Oswego, Oregon), Biosensors (Singapore), Medtronic, Stentys (Princeton, New Jersey), Daiichi Sanity, and The Medicines Company, has received research support from Abbott, Biotronik, Sadra Medical (Campbell, California), Stentys, and Icon (Dublin, Ireland), and is on the advisory board of Biotronik and Abbott. Dr. Capodanno has received speaker's honoraria from Eli Lilly and Astra-Zeneca (Wilmington, Delaware). Dr. Moses is a consultant for Cordis and Boston Scientific (Natick, Massachusetts). All other authors have reported that they have no relations relevant to the contents of this report to disclose. NR 28 TC 3 Z9 3 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 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2014 VL 113 IS 8 BP 1348 EP 1355 DI 10.1016/j.amjcard.2014.01.409 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AF3YG UT WOS:000334648000013 PM 24581924 ER PT J AU Bentley-Lewis, R Powe, C Ankers, E Wenger, J Ecker, J Thadhani, R AF Bentley-Lewis, Rhonda Powe, Camille Ankers, Elizabeth Wenger, Julia Ecker, Jeffiey Thadhani, Ravi TI Effect of Race/Ethnicity on Hypertension Risk Subsequent to Gestational Diabetes Mellitus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NEW-YORK-CITY; CARDIOVASCULAR-DISEASE; PREGNANT-WOMEN; PREVALENCE; COHORT; PREECLAMPSIA; ADULTS; TRENDS AB Gestational diabetes mellitus (GDM) prevalence is greater in racially/ethnically diverse groups compared with non-Hispanic white populations. Although race has been shown to modify other cardiovascular disease risk factors in postpartum women, the role of race/ ethnicity on GDM and subsequent hypertension has yet to be examined. The aim of this study was to evaluate the impact of race/ethnicity in relation to GDM and subsequent hypertension in a retrospective analysis of women who delivered at Massachusetts General Hospital from 1998 to 2007. Multivariate analyses were used to determine the associations between GDM and (1) race/ethnicity, (2) hypertension, and (3) the interaction with hypertension and race/ethnicity. Women were monitored for a median of 3.8 years from the date of delivery. In our population of 4,010 women, GDM was more common in nonwhite participants (p<0.0001). GDM was also associated with hypertension subsequent to delivery after adjusting for age, race, parity, first-trimester systolic blood pressure, body mass index, maternal gestational weight gain, and preeclampsia (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.28 to 2.37, p=0.0004). Moreover, Hispanic (HR 3.25, 95% CI 1.85 to 5.72, p<0.0001) and white (HR 1.68, 95% CI 1.10 to 2.57, p=0.02) women with GDM had greater hypertension risk relative to their race/ethnicity specific counterparts without GDM in race-stratified multivariable analyses. In conclusion, Hispanic women compared with white women have an increased risk of hypertension. Hispanic and white women with GDM are at a greater risk for hypertension compared with those without GDM. Because the present study may have had limited power to detect effects among black and Asian women with GDM, further research is warranted to elucidate the need for enhanced hypertension risk surveillance in these young women. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bentley-Lewis, Rhonda] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Powe, Camille; Ankers, Elizabeth; Wenger, Julia; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Ecker, Jeffiey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Bentley-Lewis, R (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM Bentley-Lewis.Rhonda@mgh.harvard.edu FU National Institutes of Health (NIB), Bethesda, Maryland [1K23RR023333, 1R03DK096152]; Robert Wood Johnson Foundation's Harold Amos Medical Faculty Development Program, Princeton, New Jersey; Howard Hughes Medical Institute Medical Research Fellowship, Chevy Chase, Maryland; NIH, Bethesda, Maryland [K24 DK094872] FX This study was supported in part by grants 1K23RR023333 and 1R03DK096152 from the National Institutes of Health (NIB), Bethesda, Maryland and the Robert Wood Johnson Foundation's Harold Amos Medical Faculty Development Program, Princeton, New Jersey awarded to RB-L; the Howard Hughes Medical Institute Medical Research Fellowship, Chevy Chase, Maryland 2009 to 2010, awarded to CP; and grant K24 DK094872 from the NIH, Bethesda, Maryland awarded to RT. The study was conducted entirely in Boston, Massachusetts. NR 21 TC 11 Z9 12 U1 2 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2014 VL 113 IS 8 BP 1364 EP 1370 DI 10.1016/j.amjcard.2014.01.411 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AF3YG UT WOS:000334648000016 PM 24576544 ER PT J AU Middelbeek, RJW Abrahamson, MJ AF Middelbeek, Roeland J. W. Abrahamson, Martin J. TI Diabetes, Prediabetes, and Glycemic Control in the United States: Challenges and Opportunities SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Abrahamson, Martin J.] Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Abrahamson, MJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM martin.abrahamson@joslin.harvard.edu NR 10 TC 2 Z9 3 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2014 VL 160 IS 8 BP 572 EP + DI 10.7326/M14-0539 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AG0ZE UT WOS:000335143700010 PM 24733201 ER PT J AU Eubank, KJ Covinsky, KE AF Eubank, Kathryn J. Covinsky, Kenneth E. TI Delirium Severity in the Hospitalized Patient: Time to Pay Attention SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Eubank, KJ (reprint author), 4150 Clement St,Bldg 203,Room 1B-77, San Francisco, CA 94121 USA. EM kathryn.eubank@ucsf.edu FU NIA NIH HHS [K24AG029812, P30AG044281, P30 AG044281, K24 AG029812] NR 7 TC 1 Z9 1 U1 0 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2014 VL 160 IS 8 BP 574 EP + DI 10.7326/M14-0553 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AG0ZE UT WOS:000335143700011 PM 24733202 ER PT J AU Bandyopadhyay, S Rogers, JT AF Bandyopadhyay, Sanghamitra Rogers, Jack T. TI Alzheimer's disease therapeutics targeted to the control of amyloid precursor protein translation: Maintenance of brain iron homeostasis SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE Alzheimer's disease; Amyloid precursor protein; Brain iron homeostasis ID APP-MESSENGER-RNA; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT; MOUSE MODEL; ALPHA-SYNUCLEIN; 5'UNTRANSLATED REGION; PARKINSONS-DISEASE; LOCUS DUPLICATION; OXIDATIVE STRESS; BETA PEPTIDE AB The neurotoxicity of amyloid beta (A beta), a major cleavage product of the amyloid precursor protein (APP), is enhanced by iron, as found in the amyloid plaques of Alzheimer's disease (AD) patients. By contrast, the long-known neuroprotective activity of APP is evident after alpha-secretase cleavage of the precursor to release sAPP alpha, and depends on the iron export actions of APP itself. The latter underlie its neurotrophic and protective effects in facilitating the homeostatic actions of ferroportin mediated-iron export. Thus APP-dependent iron export may alleviate oxidative stress by minimizing labile iron thus protecting neurons from iron overload during stroke and hemorrhage. Consistent with this, altered phosphorylation of iron-regulatory protein-1 (IRP1) and its signaling processes play a critical role in modulating APP translation via the 5' untranslated region (5'UTR) of its transcript. The APP 5'UTR region encodes a functional iron-responsive element (IRE) RNA stem loop that represents a potential target for modulating APP production. Targeted regulation of APP gene expression via the modulation of 5'UTR sequence function represents a novel approach for the potential treatment of AD since altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. Approved drugs including paroxetine and desferrioxamine and several novel compounds have been identified that suppress abnormal metal-promoted A beta accumulation with a subset of these acting via APP 5'UTR-dependent mechanisms to modulate APP translation and cleavage to generate the non-toxic sAPP alpha. (C) 2014 Elsevier Inc. All rights reserved. C1 [Bandyopadhyay, Sanghamitra; Rogers, Jack T.] Massachusetts Gen Hosp East, Dept Psychiat Neurosci, Neurochem Lab, Charlestown, MA 02129 USA. RP Rogers, JT (reprint author), Massachusetts Gen Hosp East, Dept Psychiat Neurosci, Neurochem Lab, Charlestown, MA 02129 USA. EM jrogers@partners.org OI Bandyopadhyay, Sanghamitra /0000-0002-1490-3599 FU NIH [R21 NS077079, R21 NS064853]; Zenith Grant from the Alzheimer's Association FX Dr. Jack Rogers was supported by R21 grants R21 NS077079 and R21 NS064853 from the NIH, and a Zenith Grant from the Alzheimer's Association. NR 105 TC 11 Z9 14 U1 0 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 2014 VL 88 IS 4 SI SI BP 486 EP 494 DI 10.1016/j.bcp.2014.01.032 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF8PF UT WOS:000334977400006 PM 24513321 ER PT J AU Hickman, SE El Khoury, J AF Hickman, Suzanne E. El Khoury, Joseph TI TREM2 and the neuroimmunology of Alzheimer's disease SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Microglia; Alzheimer's disease; TREM2; Neurolmmunology ID AMYLOID-PRECURSOR-PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NECROSIS-FACTOR-ALPHA; TRANSGENIC MICE; INTERFERON-GAMMA; BETA-SECRETASE; CUTTING EDGE; PPAR-GAMMA; A-BETA; RECEPTOR AB Late-onset Alzheimer's disease (AD) is a sporadic disorder with increasing prevalence in aging. The epsilon 4 allele of Apolipoprotein E(ApoE epsilon 4) was the only known major risk factor for late onset AD. Recently, two groups of investigators independently identified variants of the TREM2 gene, encoding triggering receptor expressed on myeloid cells 2 as causing increased susceptibility to late onset AD with an odds ratio similar to that of ApoE epsilon 4. TREM2 is a receptor expressed on innate immune cells. Using a novel technology called Direct RNA Sequencing wedetermined the quantitative transcriptome of microglia, the principal innate neuroimmune cells and confirmed that TREM2 is a major microglia-specific gene in the central nervous system. Over the past several years we have shown that microglia play a dichotomous role in AD. Microglia can be protective and promote phagocytosis, degradation and ultimately clearance of A beta, the pathogenic protein deposited in the brains of Alzheimer's patients. However, with disease progression, microglia become dysfunctional, release neurotoxins, lose their ability to clear A beta and produce pro-inflammatory cytokines that promote A production and accumulation. TREM2 has been shown to regulate the phagocytic ability of myeloid cells and their inflammatory response. Here we propose that the mechanism(s) by which TREM2 variants cause Alzheimer's disease are via down regulation of the A beta phagocytic ability of microglia and by dysregulation of the pro-inflammatory response of these cells. Based on our discussion we propose that TREM2 is a potential therapeutic target for stopping ordelaying progression of AD. (C) 2014 Elsevier Inc. All rights reserved.' C1 [Hickman, Suzanne E.; El Khoury, Joseph] Harvard Univ, Ctr Immunol & Inflammatory Dis, Sch Med, Boston, MA 02115 USA. [El Khoury, Joseph] Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. RP El Khoury, J (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St, Charlestown, MA 02129 USA. EM jelkhoury@partners.org FU NINDS [NS059005]; NIA [AG032349] FX This work was supported by grants NS059005 from NINDS and AG032349 from NIA to JEK. NR 47 TC 39 Z9 40 U1 7 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 2014 VL 88 IS 4 SI SI BP 495 EP 498 DI 10.1016/j.bcp.2013.11.021 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AF8PF UT WOS:000334977400007 PM 24355566 ER PT J AU Ko, JJ Choueiri, TK Rini, BI Lee, JL Kroeger, N Srinivas, S Harshman, LC Knox, JJ Bjarnason, GA MacKenzie, MJ Wood, L Vaishampayan, UN Agarwal, N Pal, SK Tan, MH Rha, SY Yuasa, T Donskov, F Bamias, A Heng, DYC AF Ko, J. J. Choueiri, T. K. Rini, B. I. Lee, J-L Kroeger, N. Srinivas, S. Harshman, L. C. Knox, J. J. Bjarnason, G. A. MacKenzie, M. J. Wood, L. Vaishampayan, U. N. Agarwal, N. Pal, S. K. Tan, M-H Rha, S. Y. Yuasa, T. Donskov, F. Bamias, A. Heng, D. Y. C. TI First-, second-, third-line therapy for mRCC: benchmarks for trial design from the IMDC SO BRITISH JOURNAL OF CANCER LA English DT Article DE metastatic renal cell carcinoma; targeted molecular therapy; outcomes assessment; overall survival; progression-free survival; mTOR inhibitor; VEGF inhibitor; benchmarks; international metastatic renal cell cancer database consortium ID RENAL-CELL CARCINOMA; DOUBLE-BLIND; PHASE-III; SURVIVAL; SUNITINIB; SORAFENIB; PROGRESSION; PAZOPANIB; ERA AB Background: Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design. Methods: Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria. Results: In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months. Conclusions: Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials. C1 [Ko, J. J.; Kroeger, N.; Heng, D. Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Choueiri, T. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rini, B. I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Lee, J-L] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Kroeger, N.] Univ Med Greifswald, Dept Urol, Greifswald, Germany. [Srinivas, S.] Stanford Med Ctr, Div Oncol, Stanford, CA USA. [Harshman, L. C.] Stanford Sch Med, Stanford Canc Inst, Div Oncol, Stanford, CA USA. [Knox, J. J.] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med, Toronto, ON, Canada. [Bjarnason, G. A.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [MacKenzie, M. J.] London Hlth Sci Ctr, London, ON, Canada. [Wood, L.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Wood, L.] Dalhousie Univ, Halifax, NS, Canada. [Vaishampayan, U. N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Agarwal, N.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Pal, S. K.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Tan, M-H] Natl Canc Ctr, Inst Bioengn & Nanotechnol, Singapore, Singapore. [Rha, S. Y.] Yonsei Univ Hosp, Seoul, South Korea. [Yuasa, T.] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo, Japan. [Donskov, F.] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Bamias, A.] Alexandra Peripheral Gen Hosp, Athens, Greece. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU NCI NIH HHS [P30 CA022453] NR 27 TC 23 Z9 23 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 15 PY 2014 VL 110 IS 8 BP 1917 EP 1922 DI 10.1038/bjc.2014.25 PG 6 WC Oncology SC Oncology GA AF3CA UT WOS:000334587900001 PM 24691425 ER PT J AU Yaffe, K Vittinghoff, E Pletcher, MJ Hoang, TD Launer, LJ Whitmer, R Coker, LH Sidney, S AF Yaffe, Kristine Vittinghoff, Eric Pletcher, Mark J. Hoang, Tina D. Launer, Lenore J. Whitmer, Rachel Coker, Laura H. Sidney, Stephen TI Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function SO CIRCULATION LA English DT Article DE blood pressure; cholesterol; cognition; glucose; risk factors ID CORONARY CALCIUM LATER; LATE-LIFE; ALZHEIMERS-DISEASE; BLOOD-PRESSURE; YOUNG-ADULTS; TEST-PERFORMANCE; DEMENTIA; CHOLESTEROL; HEALTH; AGE AB Background Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife. Methods and Results In a prospective study of 3381 adults (age, 18-30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010-2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized z scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (P<0.05 for all). Fewer significant associations were observed for cholesterol. Conclusions Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine; Vittinghoff, Eric; Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Pletcher, Mark J.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Hoang, Tina D.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Whitmer, Rachel; Sidney, Stephen] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Coker, Laura H.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu FU National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA; NHLBI [AG0005] FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. NR 50 TC 37 Z9 39 U1 0 U2 13 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 APR 15 PY 2014 VL 129 IS 15 BP 1560 EP 1567 DI 10.1161/CIRCULATIONAHA.113.004798 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AE9II UT WOS:000334321100009 PM 24687777 ER PT J AU Yan, TD Tian, DH LeMaire, SA Hughes, GC Chen, EP Misfeld, M Griepp, RB Kazui, T Bannon, PG Coselli, JS Elefteriades, JA Kouchoukos, NT Underwood, MJ Mathew, JP Mohr, FW Oo, A Sundt, TM Bavaria, JE Di Bartolomeo, R Di Eusanio, M Trimarchi, S AF Yan, Tristan D. Tian, David H. LeMaire, Scott A. Hughes, G. Chad Chen, Edward P. Misfeld, Martin Griepp, Randall B. Kazui, Teruhisa Bannon, Paul G. Coselli, Joseph S. Elefteriades, John A. Kouchoukos, Nicholas T. Underwood, Malcolm J. Mathew, Joseph P. Mohr, Friedrich-Wilhelm Oo, Aung Sundt, Thoralf M. Bavaria, Joseph E. Di Bartolomeo, Roberto Di Eusanio, Marco Trimarchi, Santi CA Int Aortic Arch Surg Study Grp TI Standardizing Clinical End Points in Aortic Arch Surgery A Consensus Statement From the International Aortic Arch Surgery Study Group SO CIRCULATION LA English DT Article DE aorta; thoracic; consensus; surgical procedures; operative ID HYPOTHERMIC CIRCULATORY ARREST; RETROGRADE CEREBRAL PERFUSION; ACUTE KIDNEY INJURY; TEMPORARY NEUROLOGICAL DYSFUNCTION; CORONARY-ARTERY BYPASS; ACUTE-RENAL-FAILURE; CARDIAC-SURGERY; RIFLE CRITERIA; GRADING SYSTEM; SURGICAL COMPLICATIONS C1 [Yan, Tristan D.; Tian, David H.; Bannon, Paul G.] Macquarie Univ, Collaborat Res CORE Grp, Sydney, NSW 2109, Australia. [Yan, Tristan D.; Bannon, Paul G.] Univ Sydney, Royal Prince Alfred Hosp, Dept Cardiothorac Surg, Sydney, NSW 2006, Australia. [LeMaire, Scott A.; Coselli, Joseph S.] St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX USA. [LeMaire, Scott A.; Coselli, Joseph S.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77030 USA. [Hughes, G. Chad; Mathew, Joseph P.] Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA. [Hughes, G. Chad; Mathew, Joseph P.] Duke Univ, Med Ctr, Div Cardiothorac Anesthesiol, Durham, NC USA. [Chen, Edward P.] Emory Univ, Sch Med, Div Cardiothorac Surg, Atlanta, GA 30322 USA. [Misfeld, Martin; Mohr, Friedrich-Wilhelm] Univ Leipzig, Heart Ctr Leipzig, Dept Cardiac Surg, D-04109 Leipzig, Germany. [Griepp, Randall B.] Mt Sinai Sch Med, Dept Cardiothorac Surg, New York, NY USA. [Kazui, Teruhisa] Hokkaido Ohno Hosp, Ctr Cardiovasc, Sapporo, Hokkaido, Japan. [Elefteriades, John A.] Yale Univ, Sch Med, Sect Cardiac Surg, New Haven, CT USA. [Kouchoukos, Nicholas T.] Missouri Baptist Med Ctr, St Louis, MO USA. [Underwood, Malcolm J.] Chinese Univ Hong Kong, Div Cardiothorac Surg, Hong Kong, Hong Kong, Peoples R China. [Oo, Aung] Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Bavaria, Joseph E.] Hosp Univ Penn, Dept Cardiovasc Surg, Philadelphia, PA 19104 USA. [Di Bartolomeo, Roberto; Di Eusanio, Marco] Univ Bologna, St Orsola Malpighi Hosp, Dept Cardiovasc Surg, Bologna, Italy. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, Milan, Italy. RP Yan, TD (reprint author), Univ Sydney, Royal Prince Alfred Hosp, Dept Cardiothorac Surg, Level 6 West,Missenden Rd, Camperdown, NSW 2050, Australia. EM tristanyan@annalscts.com RI Trimarchi, Santi/J-7361-2016; Underwood, Malcolm John/L-6823-2016; OI Trimarchi, Santi/0000-0001-5996-3264; di bartolomeo, roberto/0000-0003-3965-5779 NR 49 TC 15 Z9 15 U1 0 U2 2 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 APR 15 PY 2014 VL 129 IS 15 BP 1610 EP 1616 DI 10.1161/CIRCULATIONAHA.113.006421 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AE9II UT WOS:000334321100014 PM 24733540 ER PT J AU Guridi, J Borgatello, C Scremin, OU AF Guridi, Jorge Borgatello, Conrado Scremin, Oscar U. TI Arginine NO-dependent and NO-independent effects on hemodynamics SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE L-NAME; Nitric oxide synthase; Arterial blood pressure; Cardiac output; Systemic vascular resistance ID NITRIC-OXIDE SYNTHASE; IN-VITRO; INDUCED HYPERTENSION; INDUCED HYPOTENSION; BLOOD-PRESSURE; HEART-RATE; ACTIVATION; RATS; SEX; VASODILATION AB L-arginine administration decreases mean arterial blood pressure (MABP), presumably by excess nitric oxide (NO) synthesis. However, some reports indicate that D-arginine, not a substrate of NO synthase (NOS), also induces hypotension. To clarify this phenomenon, the hemodynamic effects of L- and D-arginine and their modification by NOS inhibition with L-nitroarginine methyl ester (L-NAME) were assessed. MABP, cardiac output, stroke volume, heart rate and systemic vascular resistance were recorded in Sprague-Dawley rats under urethane or ketamine/diazepam anesthesia, with or without blockade of NO synthesis by L-NAME. Both stereoisomers of arginine induced a close-related drop in MABP of similar magnitude and time course, but recovery from hypotension was slower in L-arginine than in D-arginine. The hypotension induced by both stereoisomers was clue to a decrease in systemic vascular resistance (SVR) with increase in cardiac output (CO) and stroke volume (SV). Administration of L-NAME induced a pronounced increase in MABP and SVR, with decreases in CO and heart rate (HR). Infusion of l-arginine after I-NAME significantly decreased MABP and SVR at the highest dose while D-arginine failed to do so. After I-NAME, MABP was significantly lower under L-arginine than under D-arginine at all doses. These experiments suggest a dual mechanism in the hypotensive effect of L-arginine: a NO independent action on vascular resistance shared with D-arginine, and a NO dependent mechanism that becomes evident in the presence of NOS inhibition with L-NAME. Cardiac effects of NO do not appear to play a role in L-arginine hypotension. Published by Elsevier B.V. C1 [Guridi, Jorge] Univ Nacl Rosario, Fac Ciencias Med, Dept Ciencias Fisiol, RA-2000 Rosario, Santa Fe, Argentina. [Guridi, Jorge; Borgatello, Conrado; Scremin, Oscar U.] Univ Nacl Rosario, PROFISIO, RA-2000 Rosario, Santa Fe, Argentina. [Scremin, Oscar U.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Scremin, Oscar U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Scremin, Oscar U.] Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina. RP Scremin, OU (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu FU Capacitacion e Investigacion para la Medicina Argentina-Asociacion Civil FX This work was supported with donations of equipment and supply funds from Capacitacion e Investigacion para la Medicina Argentina-Asociacion Civil, a non-profit academic organization. The authors wish to express their gratitude for the technical help provided by Manuel Chasco, Nicolas Turchi and Elisabet Bernaba, NR 29 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 EI 1879-0712 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 15 PY 2014 VL 729 BP 138 EP 143 DI 10.1016/j.ejphar.2014.01.070 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AE1WO UT WOS:000333763200019 PM 24530418 ER PT J AU Goldman, JG Williams-Gray, C Barker, RA Duda, JE Galvin, JE AF Goldman, Jennifer G. Williams-Gray, Caroline Barker, Roger A. Duda, John E. Galvin, James E. TI The spectrum of cognitive impairment in Lewy body diseases SO MOVEMENT DISORDERS LA English DT Review DE dementia; Parkinson's disease; cognition; executive function; mild cognitive impairment ID SOCIETY TASK-FORCE; NEWLY-DIAGNOSED PATIENTS; SLEEP BEHAVIOR DISORDER; POPULATION-BASED COHORT; MINI-MENTAL-STATE; 5-YEAR FOLLOW-UP; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; DELUSIONAL MISIDENTIFICATION; NEURODEGENERATIVE DISEASE AB Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson's disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. It is now recognized that cognitive dysfunction occurs not only in more advanced Parkinson's disease but also in early, untreated patients and even in those patients with pre-motor syndromes, such as rapid eye movement behavior disorder and hyposmia. In recent years, the concept of mild cognitive impairment as a transitional or pre-dementia state in Parkinson's disease has emerged. This has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson's disease, but has also raised questions regarding the usefulness of this concept and its application in clinical and research settings. In addition, the conundrum of whether Parkinson's disease dementia and dementia with Lewy bodies represent the same or different entities remains unresolved. Although these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other elements, such as timing of cognitive, behavioral, and motor symptoms; medication responses; and neuropathological contributions. This article examines the spectrum and evolution of cognitive impairment in Lewy body disorders and debates these controversial issues in the field using point-counterpoint approaches. (c) 2014 International Parkinson and Movement Disorder Society C1 [Goldman, Jennifer G.] Rush Univ Med Ctr, Sect Parkinson Dis & Movement Disorders, Dept Neurol Sci, Chicago, IL 60612 USA. [Williams-Gray, Caroline; Barker, Roger A.] Univ Cambridge, Dept Clin Neurosci, John Van Geest Ctr Brain Repair, Cambridge, England. [Duda, John E.] Univ Penn Perelman Sch Med, Dept Neurol, Philadelphia, PA USA. [Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Galvin, James E.] New York Univ Sch Med, Dept Neurol, New York, NY USA. [Galvin, James E.] New York Univ Sch Med, Dept Psychiat, New York, NY USA. [Galvin, James E.] New York Univ Sch Med, Dept Populat Hlth, New York, NY USA. RP Goldman, JG (reprint author), Rush Univ Med Ctr, Sect Parkinson Dis & Movement Disorders, Dept Neurol Sci, 1725 W Harrison St,Suite 755, Chicago, IL 60612 USA. EM jennifer_g_goldman@rush.edu FU NINDS NIH HHS [K23 NS060949] NR 128 TC 25 Z9 25 U1 4 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD APR 15 PY 2014 VL 29 IS 5 SI SI BP 608 EP 621 DI 10.1002/mds.25866 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA AF5DA UT WOS:000334733000004 PM 24757110 ER PT J AU Aarsland, D Taylor, JP Weintraub, D AF Aarsland, Dag Taylor, John-Paul Weintraub, Daniel TI Psychiatric issues in cognitive impairment SO MOVEMENT DISORDERS LA English DT Review DE Neuropsychiatric symptoms, Parkinson's disease, cognitive impairment, depression, psychosis, anxiety, apathy ID SLEEP BEHAVIOR DISORDER; PARKINSONS-DISEASE PATIENTS; PROGRESSIVE SUPRANUCLEAR PALSY; PLACEBO-CONTROLLED TRIAL; IMPULSE CONTROL DISORDERS; MULTIPLE SYSTEM ATROPHY; EXCESSIVE DAYTIME SLEEPINESS; CORTICOBASAL DEGENERATION; VISUAL HALLUCINATIONS; REM-SLEEP AB Neuropsychiatric symptoms (NPS) such as depression, hallucinations and apathy commonly occur in Parkinson's disease (PD) and have major clinical consequences including a negative impact on quality of life. This review discusses the epidemiology, clinical features, diagnostic procedures and treatment issues of NPS in PD and related disorders in the perspective of cognitive impairment, focusing on depression, anxiety, visual hallucinations, apathy, sleep disturbances, impulse control disorder and non-motor fluctuations. The majority of NPS are more common in PD patients with dementia, possibly related to shared underlying pathologies. Recent studies also suggest that NPS are associated with mild cognitive impairment in PD, in particular with the amnestic type. Accurate diagnosis of NPS is important but can be difficult, due to overlapping symptoms and similar appearance of symptoms of motor symptoms of parkinsonism, cognitive impairment, mood disorders and apathy. There are few systematic studies focusing on the management of NPS in PD with cognitive impairment. (c) 2014 International Parkinson and Movement Disorder Society C1 [Aarsland, Dag] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Alzheimers Dis Res Ctr, Stockholm, Sweden. [Aarsland, Dag] Stavanger Univ Hosp, Ctr Age Related Med, Stavanger, Norway. [Aarsland, Dag] Akershus Univ Hosp, Dept Geriatr Psychiat, Oslo, Norway. [Taylor, John-Paul] Inst Ageing & Hlth, Newcastle Upon Tyne, Tyne & Wear, England. [Taylor, John-Paul] Tyne & Wear NHS Trust, Newcastle Upon Tyne, Tyne & Wear, England. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Educ & Clin Ctr PADRECC, Parkinsons Dis Res, Philadelphia, PA USA. [Weintraub, Daniel] MIRECC, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Aarsland, D (reprint author), Karolinska Inst, Dept Neurobiol Care Sci & Soc, Alzheimers Dis Res Ctr, Stockholm, Sweden. EM daarsland@gmail.com OI Aarsland, Dag/0000-0001-6314-216X FU NINDS NIH HHS [P50 NS053488] NR 167 TC 23 Z9 23 U1 4 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD APR 15 PY 2014 VL 29 IS 5 SI SI BP 651 EP 662 DI 10.1002/mds.25873 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA AF5DA UT WOS:000334733000007 PM 24757113 ER PT J AU Bihorac, A Chawla, LS Shaw, AD Al-Khafaji, A Davison, DL DeMuth, GE Fitzgerald, R Gong, MN Graham, DD Gunnerson, K Heung, M Jortani, S Kleerup, E Koyner, JL Krell, K LeTourneau, J Lissauer, M Miner, J Nguyen, HB Ortega, LM Self, WH Sellman, R Shi, J Straseski, J Szalados, JE Wilber, ST Walker, MG Wilson, J Wunderink, R Zimmerman, J Kellum, JA AF Bihorac, Azra Chawla, Lakhmir S. Shaw, Andrew D. Al-Khafaji, Ali Davison, Danielle L. DeMuth, George E. Fitzgerald, Robert Gong, Michelle Ng Graham, Derrel D. Gunnerson, Kyle Heung, Michael Jortani, Saeed Kleerup, Eric Koyner, Jay L. Krell, Kenneth LeTourneau, Jennifer Lissauer, Matthew Miner, James Nguyen, H. Bryant Ortega, Luis M. Self, Wesley H. Sellman, Richard Shi, Jing Straseski, Joely Szalados, James E. Wilber, Scott T. Walker, Michael G. Wilson, Jason Wunderink, Richard Zimmerman, Janice Kellum, John A. TI Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute kidney injury; biomarkers; cell-cycle arrest; tissue inhibitor of metalloproteinases-2; insulin-like growth factor binding protein 7 ID CORONARY-HEART-DISEASE; INTERMEDIATE-RISK PATIENTS; MYOCARDIAL-INFARCTION; NIDDK WORKSHOP; GUIDELINES; CARE; MORTALITY; SURGERY; SEPSIS; DESIGN AB Rationale: We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. Objectives: We now validate a clinical test for urinary [TIMP-2].[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients. Methods: We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2].[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test. Measurements and Main Results: Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2].[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2].[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2].[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2].[IGFBP7]). Conclusions: Urinary [TIMP-2].[IGFBP7] greater than 0.3 (ng/ml) (2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962). C1 Univ Florida, Dept Anesthesiol, Gainesville, FL USA. [Chawla, Lakhmir S.; Davison, Danielle L.] George Washington Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Washington, DC 20037 USA. [Shaw, Andrew D.] Vanderbilt Univ, Ctr Med, Dept Anesthesiol, Nashville, TN 37232 USA. [Al-Khafaji, Ali] Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA USA. [DeMuth, George E.] Stat Tech Serv LLC, Chapel Hill, NC USA. [Fitzgerald, Robert] Univ Calif San Diego, San Diego, CA 92103 USA. [Gong, Michelle Ng] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Graham, Derrel D.] Louisiana State Univ, Shreveport, LA 71105 USA. [Gunnerson, Kyle] Virginia Commonwealth Univ, Dept Anesthesiol, Richmond, VA USA. [Gunnerson, Kyle] Virginia Commonwealth Univ, Dept Emergency Med, Richmond, VA USA. [Heung, Michael] Univ Michigan, Div Nephrol, Ann Arbor, MI 48109 USA. [Jortani, Saeed] Univ Louisville, Dept Pathol, Louisville, KY 40292 USA. [Kleerup, Eric] Univ Calif Los Angeles, Div Pulm & Crit Care, Los Angeles, CA USA. [Koyner, Jay L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Krell, Kenneth] Eastern Idaho Med Consultants LLC, Idaho Falls, ID USA. [LeTourneau, Jennifer] Portland VA Med Ctr, Portland, OR USA. [Lissauer, Matthew] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. [Miner, James] Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA. [Nguyen, H. Bryant] Loma Linda Univ, Loma Linda, CA 92350 USA. [Ortega, Luis M.] AGH Nephrol Associates, Dept Nephrol, Pittsburgh, PA USA. [Self, Wesley H.] Vanderbilt Univ, Sch Med, Dept Emergency Med, Nashville, TN 37212 USA. [Sellman, Richard] Int Heart Inst Montana, Missoula, MT USA. [Shi, Jing; Walker, Michael G.] Stat Consultant, Carlsbad, CA USA. [Straseski, Joely] Univ Utah, Salt Lake City, UT USA. [Straseski, Joely] ARUP Labs, Salt Lake City, UT USA. [Szalados, James E.] Rochester Gen Med, Rochester, NY USA. [Wilber, Scott T.] Summa Hlth Syst Akron City Hosp, Dept Emergency Med, Akron, OH USA. [Wilson, Jason] Tampa Gen Hosp, Tampa, FL 33606 USA. [Wunderink, Richard] Northwestern Univ, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. [Zimmerman, Janice] Methodist Hosp, Houston, TX 77030 USA. [Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15261 USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Sch Med, CRISMA Ctr, Ctr Crit Care Nephrol,Dept Crit Care Med, Room 604 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu OI Lissauer, Matthew/0000-0002-6008-9778; Wunderink, Richard/0000-0002-8527-4195 FU Astute Medical, San Diego, CA FX Supported by Astute Medical, San Diego, CA. NR 38 TC 107 Z9 108 U1 2 U2 9 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 APR 15 PY 2014 VL 189 IS 8 BP 932 EP 939 DI 10.1164/rccm.201401-0077OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AF0KQ UT WOS:000334403100010 PM 24559465 ER PT J AU Ivers, LC Teng, JE Jerome, JG Bonds, M Freedberg, KA Franke, MF AF Ivers, Louise C. Teng, Jessica E. Jerome, J. Gregory Bonds, Matthew Freedberg, Kenneth A. Franke, Molly F. TI A Randomized Trial of Ready-to-Use Supplementary Food Versus Corn-Soy Blend Plus as Food Rations for HIV-Infected Adults on Antiretroviral Therapy in Rural Haiti SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; food security; food insecurity; nutrition; macronutrient supplement ID DISEASE PROGRESSION; VIRAL LOAD; INSECURITY; INDIVIDUALS; SUPPRESSION; NUTRITION; ADHERENCE; HIV/AIDS; OUTCOMES; HEALTH AB Background. The epidemics of food insecurity, malnutrition, and human immunodeficiency virus (HIV) frequently overlap. HIV treatment programs increasingly provide nutrient-dense ready-to-use supplementary foods (RUSFs) to patients living with HIV and food insecurity, but in the absence of wasting, it is not known if RUSF confers benefit above less costly food commodities. Methods. We performed a randomized trial in rural Haiti comparing an RUSF with less costly corn-soy blend plus (CSB+) as a monthly supplement to patients with HIV infection who were on antiretroviral therapy (ART) <24 months prior to study start. We compared 6- and 12-month outcomes by ration type in terms of immunologic response, body mass index (BMI), adherence to ART, general health quality of life, household food insecurity, and household wealth. Results. A cohort of 524 patients with HIV receiving ART was randomized and followed over time. Median CD4 cell count at baseline was 339 cells/mu L (interquartile range [IQR], 197-475 cells/mu L) for the CSB+ group, and 341 cells/mu L (IQR, 213-464/mu L) for the RUSF group. Measured outcomes improved from baseline over time, but there were no statistically significant differences in change for BMI, household wealth index, hunger, general health perception score, or adherence to ART by ration type at 6 or 12 months. The RUSF group had higher CD4 count at 12 months, but this was also not statistically significant. Conclusions. In 12 months of follow-up, there was no statistically significant difference in outcomes between those receiving RUSF-based compared with CSB+-based rations in a cohort of HIV-infected adults on ART in rural Haiti. C1 [Ivers, Louise C.; Teng, Jessica E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Ivers, Louise C.; Teng, Jessica E.; Franke, Molly F.] Harvard Univ, Partners Hlth, Sch Med, Boston, MA 02115 USA. [Ivers, Louise C.; Bonds, Matthew; Franke, Molly F.] Harvard Univ, Dept Global Hlth & Social Med, Sch Med, Boston, MA 02115 USA. [Jerome, J. Gregory] Zanmi Lasante, St Marc, Haiti. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Gen Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Infect Dis, Boston, MA 02114 USA. RP Ivers, LC (reprint author), Brigham & Womens Hosp, 641 Huntington Ave,4th Floor, Boston, MA 02115 USA. EM livers@pih.org FU National Institute of Child Health and Human Development at the National Institutes of Health [R01HD057627]; Global Health Research Core at the Department of Global Health and Social Medicine, Harvard Medical School; Harvard University Center for AIDS Research, a National Institutes of Health [P30AI060354] FX This study was funded by the National Institute of Child Health and Human Development at the National Institutes of Health (grant number R01HD057627 to L. C. I.). M. F. F. was supported by the Global Health Research Core at the Department of Global Health and Social Medicine, Harvard Medical School. Support was also provided by the Harvard University Center for AIDS Research, a National Institutes of Health funded program (grant number P30AI060354). NR 37 TC 8 Z9 8 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 APR 15 PY 2014 VL 58 IS 8 BP 1176 EP 1184 DI 10.1093/cid/ciu028 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AE6OP UT WOS:000334113700027 PM 24536058 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 Statistical Issues When Searching for Predictors of Post-Lyme Disease Symptoms reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID ERYTHEMA MIGRANS C1 [Strle, Klemen; Drouin, Elise E.; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol,Med Sch, 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 NR 5 TC 0 Z9 0 U1 1 U2 2 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 APR 15 PY 2014 VL 58 IS 8 BP 1200 EP 1200 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AE6OP UT WOS:000334113700034 PM 24470277 ER PT J AU Chakkalakal, JV Christensen, J Xiang, WY Tierney, MT Boscolo, FS Sacco, A Brack, AS AF Chakkalakal, Joe V. Christensen, Josef Xiang, Wanyi Tierney, Mathew T. Boscolo, Francesca S. Sacco, Alessandra Brack, Andrew S. TI Early forming label-retaining muscle stem cells require p27(kip1) for maintenance of the primitive state SO DEVELOPMENT LA English DT Article DE Muscle; Quiescence; Regeneration; Satellite cell; Self-renewal; Stem cell; Mouse ID ADULT SATELLITE CELLS; TEMPLATE DNA STRANDS; SKELETAL-MUSCLE; SELF-RENEWAL; DETERMINATION GENE; PROGENITOR CELLS; CYCLE REGULATION; MYOGENIC CELLS; REGENERATION; QUIESCENCE AB Across different niches, subsets of highly functional stem cells are maintained in a relatively dormant rather than proliferative state. Our understanding of proliferative dynamics in tissue-specific stem cells during conditions of increased tissue turnover remains limited. Using a TetO-H2B-GFP reporter of proliferative history, we identify skeletal muscle stem cell, or satellite cells, that retain (LRC) or lose (non LRC) the H2B-GFP label. We show in mice that LRCs and nonLRCs are formed at birth and persist during postnatal growth and adult muscle repair. Functionally, LRCs and nonLRCs are born equivalent and transition during postnatal maturation into distinct and hierarchically organized subsets. Adult LRCs give rise to LRCs and nonLRCs; the former are able to self-renew, whereas the latter are restricted to differentiation. Expression analysis revealed the CIP/KIP family members p21(cip1) (Cdkn1a) and p27(kip1) (Cdkn1b) to be expressed at higher levels in LRCs. In accordance with a crucial role in LRC fate, loss of p27(kip1) promoted proliferation and differentiation of LRCs in vitro and impaired satellite cell self-renewal after muscle injury. By contrast, loss of p21(cip1) only affected nonLRCs, in which myogenic commitment was inhibited. Our results provide evidence that restriction of self-renewal potential to LRCs is established early in life and is maintained during increased tissue turnover through the cell cycle inhibitor p27(kip1). They also reveal the differential role of CIP/KIP family members at discrete steps within the stem cell hierarchy. C1 [Chakkalakal, Joe V.; Christensen, Josef; Xiang, Wanyi; Brack, Andrew S.] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Christensen, Josef] Univ Copenhagen, Fac Hlth & Med Sci, DK-1870 Copenhagen, Denmark. [Tierney, Mathew T.; Boscolo, Francesca S.; Sacco, Alessandra] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA. [Brack, Andrew S.] Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Brack, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM brack.andrew@mgh.harvard.edu OI Chakkalakal, Joe/0000-0002-8440-7312 FU National Institutes of Health (NIH) [R01 AR060868, R01 AR061002]; Muscular Dystrophy Association; Massachusetts General Hospital Postdoctoral award; Graduate Fellowship from Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Sanford-Burnham Medical Research Institute start-up funds, Ellison Medical Foundation [AG-NS-0843-11]; NIH [AR061303 P30] FX This work was supported by grants from the National Institutes of Health (NIH) [R01 AR060868, R01 AR061002] and Muscular Dystrophy Association to A. S. B.; Massachusetts General Hospital Postdoctoral award to J.V.C.; Graduate Fellowship from Faculty of Health and Medical Sciences, University of Copenhagen, Denmark to J.C.; Sanford-Burnham Medical Research Institute start-up funds, Ellison Medical Foundation [AG-NS-0843-11] and NIH [AR061303 P30] grants to A. S. Deposited in PMC for immediate release. NR 57 TC 20 Z9 20 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD APR 15 PY 2014 VL 141 IS 8 BP 1649 EP 1659 DI 10.1242/dev.100842 PG 11 WC Developmental Biology SC Developmental Biology GA AE9RY UT WOS:000334347900005 PM 24715455 ER PT J AU Kourjian, G Xu, Y Mondesire-Crump, I Shimada, M Gourdain, P Le Gall, S AF Kourjian, Georgio Xu, Yang Mondesire-Crump, Ijah Shimada, Mariko Gourdain, Pauline Le Gall, Sylvie TI Sequence-Specific Alterations of Epitope Production by HIV Protease Inhibitors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; T-CELL RESPONSES; REVERSE-TRANSCRIPTASE INHIBITORS; RESOURCE-LIMITED SETTINGS; MULTIPLE-MYELOMA CELLS; ANTIRETROVIRAL THERAPY; ANTIGEN PRESENTATION; INDUCED HYPERLIPIDEMIA; ENDOPLASMIC-RETICULUM; THIMET OLIGOPEPTIDASE AB Ag processing by intracellular proteases and peptidases and epitope presentation are critical for recognition of pathogen-infected cells by CD8(+) T lymphocytes. First-generation HIV protease inhibitors (PIs) alter proteasome activity, but the effect of first-or second-generation PIs on other cellular peptidases, the underlying mechanism, and impact on Ag processing and epitope presentation to CTL are still unknown. In this article, we demonstrate that several HIV PIs altered not only proteasome but also aminopeptidase activities in PBMCs. Using an in vitro degradation assay involving PBMC cytosolic extracts, we showed that PIs altered the degradation patterns of oligopeptides and peptide production in a sequence-specific manner, enhancing the cleavage of certain residues and reducing others. PIs affected the sensitivity of peptides to intracellular degradation, and altered the kinetics and amount of HIV epitopes produced intracellularly. Accordingly, the endogenous degradation of incoming virions in the presence of PIs led to variations in CTL-mediated killing of HIV-infected cells. By altering host protease activities and the degradation patterns of proteins in a sequence-specific manner, HIV PIs may diversify peptides available for MHC class I presentation to CTL, alter the patterns of CTL responses, and provide a complementary approach to current therapies for the CTL-mediated clearance of abnormal cells in infection, cancer, or other immune disease. C1 [Kourjian, Georgio; Xu, Yang; Mondesire-Crump, Ijah; Shimada, Mariko; Gourdain, Pauline; Le Gall, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT & Harvard,Ragon Inst MGH, Cambridge, MA 02139 USA. RP Le Gall, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT & Harvard,Ragon Inst MGH, 400 Technol Sq, Cambridge, MA 02139 USA. EM sylvie_legall@hms.harvard.edu FU National Institute of Allergy and Infectious Diseases/National Institutes of Health [AI084753, AI084106] FX This work was supported by National Institute of Allergy and Infectious Diseases/National Institutes of Health Grants AI084753 and AI084106 (to S.L.G.). NR 81 TC 6 Z9 6 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 APR 15 PY 2014 VL 192 IS 8 BP 3496 EP 3506 DI 10.4049/jimmunol.1302805 PG 11 WC Immunology SC Immunology GA AE9GB UT WOS:000334312900006 PM 24616479 ER PT J AU Barnett, LG Simkins, HMA Barnett, BE Korn, LL Johnson, AL Wherry, EJ Wu, GF Laufer, TM AF Barnett, Lisa G. Simkins, Helen M. A. Barnett, Burton E. Korn, Lisa L. Johnson, Andy L. Wherry, E. John Wu, Gregory F. Laufer, Terri M. TI B Cell Antigen Presentation in the Initiation of Follicular Helper T Cell and Germinal Center Differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CXC CHEMOKINE RECEPTOR-5; CLASS-II EXPRESSION; MEMORY CD4 CELLS; PRESENTING CELLS; IN-VIVO; DENDRITIC CELLS; DEFICIENT MICE; BCL6 EXPRESSION; RESPONSES; ACTIVATION AB High-affinity class-switched Abs and memory B cells are products of the germinal center (GC). The CD4(+) T cell help required for the development and maintenance of the GC is delivered by follicular Th cells (T-FH), a CD4(+) Th cell subset characterized by expression of Bcl-6 and secretion of IL-21. The cellular interactions that mediate differentiation of T-FH and GC B cells remain an important area of investigation. We previously showed that MHC class II (MHCII)-dependent dendritic cell Ag presentation is sufficient for the differentiation of a T-FH intermediate (termed pre-T-FH), characterized by Bcl-6 expression but lacking IL-21 secretion. In this article, we examine the contributions of MHCII Ag presentation by B cells to T-FH differentiation and GC responses in several contexts. B cells alone do not efficiently prime naive CD4(+) T cells or induce T-FH after protein immunization; however, during lymphocytic choriomeningitis virus infection, B cells induce T-FH differentiation despite the lack of effector CD4(+) T cell generation. Still, MHCII+ dendritic cells and B cells cooperate for optimal T-FH and GC B cell differentiation in response to both model Ags and viral infection. This study highlights the roles for B cells in both CD4(+) T cell priming and T-FH differentiation, and demonstrates that different APC subsets work in tandem to mediate the GC response. C1 [Barnett, Lisa G.; Simkins, Helen M. A.; Korn, Lisa L.; Laufer, Terri M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Barnett, Lisa G.; Simkins, Helen M. A.; Barnett, Burton E.; Korn, Lisa L.; Johnson, Andy L.; Wherry, E. John; Laufer, Terri M.] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA. [Barnett, Burton E.; Johnson, Andy L.; Wherry, E. John] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Wu, Gregory F.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA. [Laufer, Terri M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Laufer, TM (reprint author), Univ Penn, Sch Med, 753 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu FU Target Identification in Lupus award from the Alliance for Lupus; Veteran's Affairs Merit Award [1I01BX000435-01]; National Institute of Neurological Disorders and Stroke Grant [5K08NS062138]; Dana Foundation; National Institutes of Health [AI083005, AI095776, AI083022, AI095608, AI082630, AI045008, HHSN266200500030C, T32 AR 0077442]; Brody Family Medical Trust FX This work was supported by a Target Identification in Lupus award from the Alliance for Lupus (to T. M. L.), Veteran's Affairs Merit Award 1I01BX000435-01 (to T. M. L.), National Institute of Neurological Disorders and Stroke Grant 5K08NS062138, grants from the Dana Foundation (to G. F. W.), National Institutes of Health Grants AI083005, AI095776, AI083022, AI095608, AI082630, AI045008, and HHSN266200500030C (all to E.J.W.) and Training Grant T32 AR 0077442 (to L. L. K.), and a fellowship from the Brody Family Medical Trust (to A.L.J.). NR 68 TC 22 Z9 23 U1 1 U2 11 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 APR 15 PY 2014 VL 192 IS 8 BP 3607 EP 3617 DI 10.4049/jimmunol.1301284 PG 11 WC Immunology SC Immunology GA AE9GB UT WOS:000334312900016 PM 24646739 ER PT J AU Leite-Morris, KA Kobrin, KL Guy, MD Young, AJ Heinrichs, SC Kaplan, GB AF Leite-Morris, Kimberly A. Kobrin, Kendra L. Guy, Marsha D. Young, Angela J. Heinrichs, Stephen C. Kaplan, Gary B. TI Extinction of opiate reward reduces dendritic arborization and c-Fos expression in the nucleus accumbens core SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Conditioned place preference extinction; Morphine; Dendrite; Nucleus accumbens; Structural plasticity; Nucleus accumbens ID CONDITIONED PLACE PREFERENCE; INDUCED MORPHOLOGICAL-CHANGES; MU-OPIOID-RECEPTORS; STRUCTURAL PLASTICITY; MORPHINE; ADDICTION; RATS; NEURONS; EXPOSURE; COCAINE AB Recurrent opiate use combined with environmental cues, in which the drug was administered, provokes cue-induced drug craving and conditioned drug reward. Drug abuse craving is frequently linked with stimuli from a prior drug-taking environment via classical conditioning and associative learning. We modeled the conditioned morphine reward process by using acquisition and extinction of conditioned place preference (CPP) in C57BL/6 mice. Mice were trained to associate a morphine injection with a drug context using a classical conditioning paradigm. In morphine conditioning (0, 0.25, 0.5, 1, 5, or 10 mg/kg) experimental mice acquired a morphine CPP dose response with 10 mg/kg as most effective. During morphine CPP extinction experiments, mice were divided into three test groups: morphine CPP followed by extinction training, morphine CPP followed by sham extinction, and saline controls. Extinction of morphine CPP developed within one extinction experiment (4 days) that lasted over two more trials (another 8 days). However, the morphine CPP/sham extinction group retained a place preference that endured through all three extinction trials. Brains were harvested following CPP extinction and processed using Golgi-Cox impregnation. Changes in dendritic morphology and spine quantity were examined in the nucleus accumbens (NAc) Core and Shell neurons. In the NAcCore only, morphine CPP/extinguished mice produced less dendritic arborization, and a decrease in neuronal activity marker c-Fos compared to the morphine CPP/sham extinction group. Extinction of morphine CPP is associated with decreased structural complexity of dendrites in the NAcCore and may represent a substrate for learning induced structural plasticity relevant to addiction. Published by Elsevier B.V. C1 [Leite-Morris, Kimberly A.; Kobrin, Kendra L.; Guy, Marsha D.; Young, Angela J.; Heinrichs, Stephen C.; Kaplan, Gary B.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Kaplan, Gary B.] VA Boston Healthcare Syst, Mental Hlth Serv, Boston, MA 02130 USA. [Leite-Morris, Kimberly A.; Kaplan, Gary B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Leite-Morris, Kimberly A.; Kobrin, Kendra L.; Kaplan, Gary B.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA. RP Leite-Morris, KA (reprint author), VA Boston Healthcare Syst 151, 150 South Huntington Ave, Boston, MA 02130 USA. EM kleitemo@bu.edu; kendrak@bu.edu; marsha.guy@gmail.com; angela.pieroniyoung@facebook.com; Stephen.Heinrichs@va.gov; Gary.Kaplan@va.gov FU Merit Award from the Department of Veterans Affairs FX This research was supported by a Merit Award from the Department of Veterans Affairs to GBK. Authors KLM and GBK designed the study. Authors GBK, KLM, and KLK wrote the manuscript. Author SCH designed, and SCH and KLK collected, the behavioral measures. MDG, AGY and KLK performed the processing and analyses of Golgi-Cox samples. KLM and SCH performed data analysis and interpretation. GBK and KLM provided a critical review for intellectual content. GBK, KLM, and KLK edited the final version. NR 38 TC 6 Z9 6 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR 15 PY 2014 VL 263 BP 51 EP 59 DI 10.1016/j.bbr.2013.12.041 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AE3NR UT WOS:000333883700007 PM 24406724 ER PT J AU Reckamp, KL Giaccone, G Camidge, DR Gadgeel, SM Khuri, FR Engelman, JA Koczywas, M Rajan, A Campbell, AK Gernhardt, D Ruiz-Garcia, A Letrent, S Liang, J Taylor, I O'Connell, JP Janne, PA AF Reckamp, Karen L. Giaccone, Giuseppe Camidge, D. Ross Gadgeel, Shirish M. Khuri, Fadlo R. Engelman, Jeff A. Koczywas, Marianna Rajan, Arun Campbell, Alicyn K. Gernhardt, Diana Ruiz-Garcia, Ana Letrent, Stephen Liang, Jane Taylor, Ian O'Connell, Joseph P. Jaenne, Pasi A. TI A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non-small cell lung cancer after failure of prior chemotherapy and erlotinib SO CANCER LA English DT Article DE adenocarcinoma; non-small cell lung cancer; nonadenocarcinoma; erlotinib; dacomitinib; PF-00299804 ID TYROSINE KINASE INHIBITORS; CLINICAL-TRIALS; EGFR; MUTATIONS; GEFITINIB; RESISTANT; THERAPY; QLQ-C30 AB BACKGROUND This phase 2 trial ( identifier NCT00548093) assessed the efficacy, safety, and impact on health-related quality of life of dacomitinib (PF-00299804), an irreversible tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, in patients with KRAS wild-type non-small cell lung cancer (NSCLC). METHODS Patients with advanced NSCLC, progression on 1 or 2 regimens of chemotherapy and erlotinib, KRAS wild-type or known EGFR-sensitizing mutant tumor, and Eastern Cooperative Oncology Group performance status of 0 to 2 received 45 mg of dacomitinib once daily continuously in 21-day cycles. RESULTS A total of 66 patients enrolled (adenocarcinoma, n = 50; those without adenocarcinoma [nonadenocarcinoma], n = 16). The objective response rate (ORR) for patients with adenocarcinoma (primary endpoint) was 5% (2 partial responses; 1-sided P = .372 for null hypothesis [H-0]: ORR <= 5%) and 6% (1 partial response) for patients with nonadenocarcinoma. Responders included: 2 of 25 EGFR mutation-positive tumors; 1 of 3 EGFR wild-type with HER2 amplification. Median progression-free survival was 12 weeks overall (n = 66) and 18 weeks (n = 26) for patients with EGFR mutation-positive tumors. Common treatment-related adverse events were of grade 1 or 2 severity, manageable with standard supportive care, and included diarrhea (grade 3 [G3], 12%), acneiform dermatitis (G3, 6%), exfoliative rash (G3, 3%), dry skin (G3, 0%), fatigue (G3, 3%), and stomatitis (G3, 2%). Six patients (9%) discontinued due to treatment-related adverse events. By patient report, NSCLC symptoms of dyspnea, cough, and pain (chest, arm/shoulder) showed improvement first observed after 3 weeks on therapy. CONCLUSIONS Dacomitinib demonstrated preliminary activity and acceptable tolerability in heavily pretreated patients, and may offer benefit in molecularly defined patient subsets. Cancer 2014;120:1145-1154. (c) 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. C1 [Reckamp, Karen L.; Koczywas, Marianna] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Giaccone, Giuseppe; Rajan, Arun] NCI, Bethesda, MD 20892 USA. [Camidge, D. Ross] Univ Colorado Denver, Aurora, CO USA. [Gadgeel, Shirish M.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Khuri, Fadlo R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Engelman, Jeff A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Campbell, Alicyn K.; Gernhardt, Diana; Liang, Jane; Taylor, Ian] Pfizer Oncol, Groton, CT USA. [Ruiz-Garcia, Ana; Letrent, Stephen] Pfizer Oncol, La Jolla, CA USA. [O'Connell, Joseph P.] Pfizer Oncol, New York, NY USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Reckamp, KL (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM kreckamp@coh.org RI Ruiz-Garcia, Ana/O-8252-2014; Giaccone, Giuseppe/E-8297-2017; OI Ruiz-Garcia, Ana/0000-0002-5462-3110; Giaccone, Giuseppe/0000-0002-5023-7562; Reckamp, Karen/0000-0002-9213-0325 FU Pfizer Inc FX This study was sponsored by Pfizer Inc. NR 25 TC 43 Z9 44 U1 0 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 APR 15 PY 2014 VL 120 IS 8 BP 1145 EP 1154 DI 10.1002/cncr.28561 PG 10 WC Oncology SC Oncology GA AE3GT UT WOS:000333865700005 PM 24501009 ER PT J AU Rudek, MA Moore, PC Mitsuyasu, RT Dezube, BJ Aboulafia, D Gerecitano, J Sullivan, R Cianfrocca, ME Henry, DH Ratner, L Haigentz, M Dowlati, A Little, RF Ivy, SP Deeken, JF AF Rudek, Michelle A. Moore, Page C. Mitsuyasu, Ronald T. Dezube, Bruce J. Aboulafia, David Gerecitano, John Sullivan, Ryan Cianfrocca, Mary E. Henry, David H. Ratner, Lee Haigentz, Missak, Jr. Dowlati, Afshin Little, Richard F. Ivy, Susan Percy Deeken, John F. TI A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus-positive patients with cancer: AIDS Malignancy Consortium trial AMC 061 SO CANCER LA English DT Article DE highly active antiretroviral therapy (HAART); clinical trial; phase 1; human immunodeficiency virus (HIV); sunitinib ID TYROSINE KINASE INHIBITOR; HIV-INFECTED INDIVIDUALS; RESISTANCE PROTEIN ABCG2; N-DESETHYL SUNITINIB; P-GLYCOPROTEIN ABCB1; RESPONSE CRITERIA; BREAST-CANCER; IN-VIVO; BRAIN ACCUMULATION; DEFINING CANCERS AB BACKGROUND The treatment of non-acquired immunodeficiency syndrome-defining cancers may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium to assess targeted therapies and HAART in human immunodeficiency virus-positive patients ( identifier: NCT00890747). METHODS In a modified phase 1 study of sunitinib, patients were stratified into 2 treatment arms based on whether they were receiving therapy with ritonavir, a potent CYP3A4 inhibitor. Patients in treatment arm 1 (non-ritonavir HAART) received standard sunitinib dosing (50 mg/day). Treatment arm 2 (ritonavir-based HAART) used a phase 1, 3 + 3 dose escalation design (from 25 mg/day to 50 mg/day). Cycles were comprised of 4 weeks on treatment followed by a 2-week break (6 weeks total). The pharmacokinetics of sunitinib and its active metabolite (N-desethyl sunitinib) were assessed. RESULTS Nineteen patients were enrolled and were evaluable. Patients on treatment arm 1 tolerated treatment with no dose-limiting toxicity observed. In treatment arm 2, a dose-limiting toxicity was experienced at a dose of 37.5 mg, and an additional 3 of 5 patients experienced grade 3 neutropenia (toxicity graded as per National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]), an uncommon toxicity of sunitinib. No patient achieved a response, but 10 patients had stable disease, including 8 with prolonged disease stability. Efavirenz, a potent inducer of CYP3A4, resulted in increased exposure of N-desethyl sunitinib, whereas ritonavir caused decreased exposure of the metabolite. Hand-foot syndrome was associated with higher steady-state trough concentrations of sunitinib. CONCLUSIONS Patients receiving non-ritonavir-based HAART regimens tolerated standard dosing of sunitinib. Patients receiving ritonavir-based therapy who were treated with a dose of 37.5 mg/day experienced higher toxicities. Dose reductions of sunitinib to 37.5 mg may be warranted in patients receiving ritonavir. Cancer 2014;120:1194-1202. (c) 2014 American Cancer Society. C1 [Rudek, Michelle A.] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Moore, Page C.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Mitsuyasu, Ronald T.] Univ Calif Los Angeles, Dept Med, Ctr Clin AIDS Res & Educ CARE Ctr, Los Angeles, CA 90024 USA. [Dezube, Bruce J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Aboulafia, David] Univ Washington, Virginia Mason Med Ctr, Div Hematol & Oncol, Seattle, WA 98195 USA. [Gerecitano, John] Mem Sloan Kettering Canc Ctr, Dept Med, Lymphoma Serv, New York, NY 10021 USA. [Sullivan, Ryan] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Cianfrocca, Mary E.] Northwestern Univ, Chicago, IL 60611 USA. [Henry, David H.] Penn Hosp, Dept Med, Philadelphia, PA 19107 USA. [Ratner, Lee] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Haigentz, Missak, Jr.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Oncol, Bronx, NY 10467 USA. [Dowlati, Afshin; Ivy, Susan Percy] Case Comprehens Canc Ctr, Dept Med, Cleveland, OH USA. [Little, Richard F.] NCI, Canc Therapy Evaluat Program, NIH, Washington, DC USA. [Deeken, John F.] Inova Comprehens Canc & Res Inst, Div Med Oncol Hematol, Falls Church, VA 22042 USA. RP Deeken, JF (reprint author), Inova Comprehens Canc & Res Inst, 3300 Gallows Rd, Falls Church, VA 22042 USA. EM john.deeken@inova.org FU NIH/NCI [U01 CA121947, P30 CA006973, UL1 RR025005, 1S10RR026824-01, UL1TR000124, K12 CA132783] FX The project described was supported by the NIH/NCI award to the AIDS Malignancy Consortium (U01 CA121947). Additional NIH/NCI grant support was provided as follows: Dr. Rudek - P30 CA006973, UL1 RR025005, 1S10RR026824-01; Dr. Mitsuyasu - UL1TR000124; and, Dr. Haigentz - K12 CA132783. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 32 TC 9 Z9 9 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2014 VL 120 IS 8 BP 1194 EP 1202 DI 10.1002/cncr.28554 PG 9 WC Oncology SC Oncology GA AE3GT UT WOS:000333865700011 PM 24474568 ER PT J AU Huang, JF Zheng, SS Liu, YF Wang, HB Chapman, J O'Connell, P Millis, M Fung, J Delmonico, F AF Huang, Jie-Fu Zheng, Shu-Sen Liu, Yong-Feng Wang, Hai-Bo Chapman, Jeremy O'Connell, Philip Millis, Michael Fung, John Delmonico, Francis TI China organ donation and transplantation update: the Hangzhou Resolution SO HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL LA English DT Editorial Material C1 [Huang, Jie-Fu] Beijing Union Med Coll Hosp, Dept Liver Surg, Natl Organ Transplant Comm, Minist Hlth, Beijing 100000, Peoples R China. [Zheng, Shu-Sen] Zhejiang Univ, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China. [Liu, Yong-Feng] China Med Univ, Hosp 1, Shenyang 110001, Peoples R China. [Wang, Hai-Bo] Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China. [Wang, Hai-Bo] China Organ Transplant Response Syst Res Ctr, Shenzhen 518000, Peoples R China. [Chapman, Jeremy; O'Connell, Philip] Univ Sydney, Westmead Millenium Inst, Ctr Renal & Transplant Res, Sydney, NSW 2006, Australia. [Millis, Michael] Univ Chicago, Sect Transplantat Liver Transplantat & Hepatobili, Chicago, IL 60637 USA. [Fung, John] Cleveland Clin, Inst Digest Dis, Dept Gen Surg, Transplant Ctr, Cleveland, OH 44106 USA. [Delmonico, Francis] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Huang, JF (reprint author), Minist Hlth, 1 Xizhimen Wai Nan Rd, Beijing 100044, Peoples R China. EM zhaohtmoh@126.com RI Fung, John/A-2679-2012 NR 2 TC 7 Z9 7 U1 1 U2 8 PU ZHEJIANG UNIV SCH MEDICINE PI HANGZHOU PA FIRST AFFILIATED HOSPITAL, 79 QINGCHUN ROAD, HANGZHOU, 310003, PEOPLES R CHINA SN 1499-3872 J9 HEPATOB PANCREAT DIS JI Hepatob. Pancreatic. Dis. Int. PD APR 15 PY 2014 VL 13 IS 2 BP 122 EP 124 DI 10.1016/S1499-3872(14)60022-9 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AE2FE UT WOS:000333787900001 PM 24686539 ER PT J AU Cao, H Yu, F Zhao, Y Scianmarello, N Lee, J Dai, WD Jen, N Beebe, T Li, RS Ebrahimi, R Chang, DS Mody, FV Pacella, J Tai, YC Hsiai, T AF Cao, Hung Yu, Fei Zhao, Yu Scianmarello, Nick Lee, Juhyun Dai, Wangde Jen, Nelson Beebe, Tyler Li, Rongsong Ebrahimi, Ramin Chang, Donald S. Mody, Freny V. Pacella, John Tai, Yu-Chong Hsiai, Tzung TI Stretchable electrochemical impedance sensors for intravascular detection of lipid-rich lesions in New Zealand White rabbits SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Stretchable micro-sensor; Electrochemical impedance spectroscopy; Balloon inflation; Atherosclerotic lesions; New Zealand White rabbits ID ACUTE CORONARY SYNDROMES; SHEAR-STRESS; ATHEROSCLEROTIC LESIONS; ARTERY-DISEASE; OXIDIZED LDL; SPECTROSCOPY; NITRATION; CATHETER; CLASSIFICATION; INFLAMMATION AB Flexible electronics have enabled catheter-based intravascular sensing. However, real-time interrogation of unstable plaque remains an unmet clinical challenge. Here, we demonstrate the feasibility of stretchable electrochemical impedance spectroscopy (EIS) sensors for endoluminal investigations in New Zealand White (NZW) rabbits on diet-induced hyperlipidemia. A parylene C (PAC)-based EIS sensor mounted on the surface of an inflatable silicone balloon affixed to the, tip of an interrogating catheter was deployed (1) on the explants of NZW rabbit aorta for detection of lipid-rich atherosclerotic lesions, and (2) on live animals for demonstration of balloon inflation and EIS measurements. An input peak-to-peak AC voltage of 10 mV and sweeping-frequency from 300 kHz to 100 Hz were delivered to the endoluminal sites. Balloon inflation allowed EIS sensors to be in contact with endoluminal surface. In the oxidized low-density-lipoprotein (oxLDL)-rich lesions from explants of fat-fed rabbits, impedance magnitude increased significantly by 1.5-fold across the entire frequency band, and phase shifted similar to 5 degrees at frequencies below 10 kHz. In the lesion-free sites of the normal diet-fed rabbits, impedance magnitude increased by 1.2-fold and phase shifted similar to 5 degrees at frequencies above 30 kHz. Thus, we demonstrate the feasibility of stretchable intravascular EIS sensors for identification of lipid rich lesions, with a translational implication for detecting unstable lesions. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved. C1 [Cao, Hung; Yu, Fei; Lee, Juhyun; Jen, Nelson; Beebe, Tyler; Li, Rongsong; Hsiai, Tzung] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Zhao, Yu; Scianmarello, Nick; Tai, Yu-Chong] CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA. [Cao, Hung; Lee, Juhyun; Jen, Nelson; Beebe, Tyler; Li, Rongsong; Ebrahimi, Ramin; Chang, Donald S.; Mody, Freny V.; Hsiai, Tzung] Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Div Cardiol,Dept Med, Los Angeles, CA USA. [Dai, Wangde] Good Samaritan Hosp, Inst Heart, Los Angeles, CA USA. [Pacella, John] Univ Pittsburgh, Sch Med, Div Cardiol, Pittsburgh, PA USA. RP Hsiai, T (reprint author), Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA 90073 USA. EM THsiai@mednet.ucla.edu FU National Institutes of Health [HL083015, HL111437] FX The authors would like to express gratitude for technical advice from Dr. David Shavelle in the Division of Cardiovascular Medicine at USC, and technical support for animal studies from Sharon Hale and Dr. Robert Klonner in the Heart Institute at Good Samaritan Medical Center, Los Angeles. This project was supported by National Institutes of Health, HL083015 (T.K.H.) and HL111437 (T.K.H. and Y.C.T.). NR 31 TC 5 Z9 5 U1 2 U2 21 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 EI 1873-4235 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD APR 15 PY 2014 VL 54 BP 610 EP 616 DI 10.1016/j.bios.2013.11.059 PG 7 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA AD2ND UT WOS:000333071500091 PM 24333932 ER PT J AU Luoto, TM Silverberg, ND Kataja, A Brander, A Tenovuo, O Ohman, J Iverson, GL AF Luoto, Teemu M. Silverberg, Noah D. Kataja, Anneli Brander, Antti Tenovuo, Olli Ohman, Juha Iverson, Grant L. TI Sport Concussion Assessment Tool 2 in a Civilian Trauma Sample with Mild Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE Military Acute Concussion Evaluation; traumatic brain injury; concussion; Sport Concussion Assessment Tool ID ERROR SCORING SYSTEM; HEAD-INJURY; INTERNATIONAL-CONFERENCE; STANDARDIZED ASSESSMENT; POSTTRAUMATIC AMNESIA; EMERGENCY-DEPARTMENT; CONSENSUS STATEMENT; ANKLE INSTABILITY; FOOTBALL PLAYERS; MANAGEMENT AB The aim of the study was to evaluate the validity of the Sport Concussion Assessment Tool-Second Edition (SCAT2) in patients with acute mild traumatic brain injuries (mTBIs) in a civilian trauma setting. In addition, the SCAT2 was compared to the Military Acute Concussion Evaluation (MACE). All the participants of the study were prospectively recruited from the emergency department of Tampere University Hospital (Tampere, Finland). Patients (n=49) between the ages of 18 and 60 years, with no premorbid medical or psychiatric conditions, who met the World Health Organization criteria for mTBI, were enrolled. Trauma controls (n=33) were recruited using similar study criteria. The main measures of the study consisted of SCAT2, MACE, and mTBI severity markers, including neuroimaging (computed tomography and conventional magnetic resonance imaging [MRI]), and 1-month clinical outcomes (postconcussion syndrome diagnosis and return to work status). The scoreable components of the SCAT2 performed variably across five dimensions of validity (diagnostic, criterion, divergent, predictive, and responsiveness). The Standardized Assessment of Concussion component reasonably discriminated mTBI patients from controls, was associated with MRI lesions, improved over time, and predicted return to work. Symptom scores differentiated patients with mTBIs from controls, and elevated initial symptom scores in patients with mTBI were associated with a greater risk of persistent postconcussion symptoms. The SCAT2 was superior to the MACE. The SCAT2 appears useful for detecting acute mTBI-related symptoms and cognitive impairment, refining prognosis, and monitoring recovery. C1 [Luoto, Teemu M.; Ohman, Juha] Tampere Univ Hosp, Dept Neurosci & Rehabil, FI-33521 Tampere, Finland. [Silverberg, Noah D.] Univ British Columbia, Dept Med, Div Phys Med & Rehabil, Vancouver, BC, Canada. [Silverberg, Noah D.] GF Strong Rehab Ctr, Vancouver, BC, Canada. [Kataja, Anneli; Brander, Antti] Tampere Univ Hosp, Dept Radiol, Med Imaging Ctr, FI-33521 Tampere, Finland. [Tenovuo, Olli] Univ Turku, Dept Neurol, FIN-20520 Turku, Finland. [Tenovuo, Olli] Turku Univ, Cent Hosp, Turku, Finland. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Home Base Program, Massachusetts Gen Hosp, Boston, MA USA. [Iverson, Grant L.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. RP Luoto, TM (reprint author), Tampere Univ Hosp, Dept Neurosci & Rehabil, POB 2000, FI-33521 Tampere, Finland. EM teemu.luoto@pshp.fi OI Luoto, Teemu/0000-0002-7329-3284; Ohman, Juha/0000-0002-6592-1367 FU Medical Research Fund of Tampere University Hospital; Maire Taponen Foundation; Emil Aaltonen Foundation; Vancouver Coastal Health Research Institute FX The authors thank research assistants Anne Simi and Marika Suopanki-Ervasti for their contribution in data collection. This study was done as part of the first author's PhD thesis research program. This study was presented at the 4th International Consensus Conference on Concussion in Sport in Zurich, November 2012. This study has been supported by the Medical Research Fund of Tampere University Hospital, the Maire Taponen Foundation, and the Emil Aaltonen Foundation. N.D.S. receives funding from the Vancouver Coastal Health Research Institute. G. L. I. notes that the views expressed in this article are those of the authors and do not reflect the official policy of the Department of Defense or U.S. government. NR 41 TC 13 Z9 13 U1 1 U2 15 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD APR 15 PY 2014 VL 31 IS 8 BP 728 EP 738 DI 10.1089/neu.2013.3174 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AD7PX UT WOS:000333457200004 PM 24502622 ER PT J AU Rodriguez, AR Muller, LPD Brecha, NC AF Rodriguez, Allen R. Mueller, Luis Perez de Sevilla Brecha, Nicholas C. TI The RNA binding protein RBPMS is a selective marker of ganglion cells in the mammalian retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE RNA-binding protein; transcription factor; amacrine cell; melanopsin; SMI-32; ganglion cell ID DISPLACED AMACRINE CELLS; OPTIC-NERVE REGENERATION; MOUSE RETINA; RAT RETINA; MORPHOLOGICAL CLASSIFICATION; QUANTITATIVE-ANALYSIS; MACAQUE MONKEY; RABBIT RETINA; CAT RETINA; ALBINO-RAT AB There are few neurochemical markers that reliably identify retinal ganglion cells (RGCs), which are a heterogeneous population of cells that integrate and transmit the visual signal from the retina to the central visual nuclei. We have developed and characterized a new set of affinity-purified guinea pig and rabbit antibodies against RNA-binding protein with multiple splicing (RBPMS). On western blots these antibodies recognize a single band at similar to 24 kDa, corresponding to RBPMS, and they strongly label RGC and displaced RGC (dRGC) somata in mouse, rat, guinea pig, rabbit, and monkey retina. RBPMS-immunoreactive cells and RGCs identified by other techniques have a similar range of somal diameters and areas. The density of RBPMS cells in mouse and rat retina is comparable to earlier semiquantitative estimates of RGCs. RBPMS is mainly expressed in medium and large DAPI-, DRAQ5-, NeuroTrace- and NeuN-stained cells in the ganglion cell layer (GCL), and RBPMS is not expressed in syntaxin (HPC-1)-immunoreactive cells in the inner nuclear layer (INL) and GCL, consistent with their identity as RGCs, and not displaced amacrine cells. In mouse and rat retina, most RBPMS cells are lost following optic nerve crush or transection at 3 weeks, and all Brn3a-, SMI-32-, and melanopsin-immunoreactive RGCs also express RBPMS immunoreactivity. RBPMS immunoreactivity is localized to cyan fluorescent protein (CFP)-fluorescent RGCs in the B6.Cg-Tg(Thy1-CFP)23Jrs/J mouse line. These findings show that antibodies against RBPMS are robust reagents that exclusively identify RGCs and dRGCs in multiple mammalian species, and they will be especially useful for quantification of RGCs. J. Comp. Neurol. 522:1411-1443, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Rodriguez, Allen R.; Mueller, Luis Perez de Sevilla; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA 90073 USA. RP Brecha, NC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med Los Angeles, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM nbrecha@ucla.edu FU U.S. Army Medical Research & Materiel Command (USAMRMC); Telemedicine & Advanced Technology Research Center (TATRC) at Fort Detrick, MD [W81XWH-10-2-0077]; National Institutes of Health [EY04067]; National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health [P30 DK41301]; VA Merit Review FX Grant sponsor: This research and development project was conducted by the authors at the David Geffen School of Medicine at the University of California at Los Angeles and is made possible by a contract agreement 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; Grant number: W81XWH-10-2-0077; Grant sponsor: National Institutes of Health; Grant sponsor: EY04067; Grant sponsor: National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health; Grant number: P30 DK41301 (UCLA Cure Center Core); Grant sponsor: VA Merit Review (to N.C.B., who is a VA Career Research Scientist). NR 128 TC 42 Z9 43 U1 4 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 15 PY 2014 VL 522 IS 6 BP 1411 EP 1443 DI 10.1002/cne.23521 PG 33 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA AC8BB UT WOS:000332756900013 PM 24318667 ER PT J AU Lojewski, X Staropoli, JF Biswas-Legrand, S Simas, AM Haliw, L Selig, MK Coppel, SH Goss, KA Petcherski, A Chandrachud, U Sheridan, SD Lucente, D Sims, KB Gusella, JF Sondhi, D Crystal, RG Reinhardt, P Sterneckert, J Scholer, H Haggarty, SJ Storch, A Hermann, A Cotman, SL AF Lojewski, Xenia Staropoli, John F. Biswas-Legrand, Sunita Simas, Alexandra M. Haliw, Larissa Selig, Martin K. Coppel, Scott H. Goss, Kendrick A. Petcherski, Anton Chandrachud, Uma Sheridan, Steven D. Lucente, Diane Sims, Katherine B. Gusella, James F. Sondhi, Dolan Crystal, Ronald G. Reinhardt, Peter Sterneckert, Jared Schoeler, Hans Haggarty, Stephen J. Storch, Alexander Hermann, Andreas Cotman, Susan L. TI Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway SO HUMAN MOLECULAR GENETICS LA English DT Article ID PLURIPOTENT STEM-CELLS; MULTIVESICULAR BODY FORMATION; BATTEN-DISEASE; TRIPEPTIDYL-PEPTIDASE; ADENOASSOCIATED VIRUS; MOUSE MODEL; PROTEIN; YEAST; BTN1; ORTHOLOGUE AB Neuronal ceroid lipofuscinosis (NCL) comprises 13 genetically distinct lysosomal disorders primarily affecting the central nervous system. Here we report successful reprograming of patient fibroblasts into induced pluripotent stem cells (iPSCs) for the two most common NCL subtypes: classic late-infantile NCL, caused by TPP1(CLN2) mutation, and juvenile NCL, caused by CLN3 mutation. CLN2/TPP1- and CLN3-iPSCs displayed overlapping but distinct biochemical and morphological abnormalities within the endosomallysosomal system. In neuronal derivatives, further abnormalities were observed in mitochondria, Golgi and endoplasmic reticulum. While lysosomal storage was undetectable in iPSCs, progressive disease subtype-specific storage material was evident upon neural differentiation and was rescued by reintroducing the non-mutated NCL proteins. In proof-of-concept studies, we further documented differential effects of potential small molecule TPP1 activity inducers. Fenofibrate and gemfibrozil, previously reported to induce TPP1 activity in control cells, failed to increase TPP1 activity in patient iPSC-derived neural progenitor cells. Conversely, nonsense suppression by PTC124 resulted in both an increase of TPP1 activity and attenuation of neuropathology in patient iPSC-derived neural progenitor cells. This study therefore documents the high value of this powerful new set of tools for improved drug screening and for investigating early mechanisms driving NCL pathogenesis. C1 [Lojewski, Xenia; Staropoli, John F.; Biswas-Legrand, Sunita; Simas, Alexandra M.; Haliw, Larissa; Coppel, Scott H.; Goss, Kendrick A.; Petcherski, Anton; Chandrachud, Uma; Sheridan, Steven D.; Lucente, Diane; Sims, Katherine B.; Gusella, James F.; Haggarty, Stephen J.; Cotman, Susan L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lojewski, Xenia; Storch, Alexander; Hermann, Andreas] Tech Univ Dresden, Div Neurodegenerat Dis, Dept Neurol, D-01307 Dresden, Germany. [Storch, Alexander] Tech Univ Dresden, CRTD, D-01307 Dresden, Germany. [Staropoli, John F.; Selig, Martin K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Biswas-Legrand, Sunita; Chandrachud, Uma; Sheridan, Steven D.; Sims, Katherine B.; Gusella, James F.; Haggarty, Stephen J.; Cotman, Susan L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sondhi, Dolan; Crystal, Ronald G.] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10021 USA. [Reinhardt, Peter; Sterneckert, Jared; Schoeler, Hans] Max Planck Inst Mol Biomed, D-48149 Munster, Germany. [Storch, Alexander; Hermann, Andreas] German Ctr Neurodegenerat Dis DZNE Dresden, D-01307 Dresden, Germany. RP Cotman, SL (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM cotman@helix.mgh.harvard.edu RI Sterneckert, Jared/E-6802-2015; OI Scholer, Hans/0000-0003-2643-5136; Haggarty, Stephen J./0000-0002-7872-168X FU National Institutes of Health: National Institute of Neurological Disorders Stroke [R01NS073813, R01NS061848, U54NS065768, K08NS079359]; Batten Disease Support and Research Association; National Institute of Mental Health [R33MH087896]; National Contest for Life (NCL Stiftung); Tau Consortium; Massachusetts General Hospital ECOR Tosteson Award; Catherine's Hope for a Cure FX This work was supported in part by the National Institutes of Health: National Institute of Neurological Disorders & Stroke (grant number R01NS073813 to S. L. C.; grant numbers R01NS061848 U54NS065768 to R. G. C. and D. S.; and grant number K08NS079359 to J.F.S.); the Batten Disease Support and Research Association (to J.F.S., S. B. and S. L. C.); the National Institute of Mental Health (grant number R33MH087896 to S.J.H.); The National Contest for Life (NCL Stiftung; to A. S. and A. H.); the Tau Consortium (to S.J.H.); and by a Massachusetts General Hospital ECOR Tosteson Award (to J.F.S.); and by Catherine's Hope for a Cure (to K.B.S. and S.L.C.). NR 64 TC 20 Z9 20 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2014 VL 23 IS 8 BP 2005 EP 2022 DI 10.1093/hmg/ddt596 PG 18 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AD5CP UT WOS:000333269400005 PM 24271013 ER PT J AU Lee, LJ Ratner, E Uduman, M Winter, K Boeke, M Greven, KM King, S Burke, TW Underhill, K Kim, H Boulware, RJ Yu, H Parkash, V Lu, LG Gaffney, D Dicker, AP Weidhaas, J AF Lee, Larissa J. Ratner, Elena Uduman, Mohamed Winter, Kathryn Boeke, Marta Greven, Kathryn M. King, Stephanie Burke, Thomas W. Underhill, Kelly Kim, Harold Boulware, Raleigh J. Yu, Herbert Parkash, Vinita Lu, Lingeng Gaffney, David Dicker, Adam P. Weidhaas, Joanne TI The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Trials 9708 and 9905 SO PLOS ONE LA English DT Article ID LET-7 MICRORNA-BINDING; 3'-UNTRANSLATED REGION; COLORECTAL-CANCER; CISPLATIN/PACLITAXEL CHEMOTHERAPY; CLINICOPATHOLOGICAL SIGNIFICANCE; SITE POLYMORPHISM; POINT MUTATIONS; BREAST-CANCER; CARCINOMA; RISK AB Objective: To explore the association of a functional germline variant in the 39'-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials. Methods/Materials: The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type. Results: The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively, favoring the variant. Conclusions: The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology. C1 [Lee, Larissa J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Ratner, Elena; Boeke, Marta] Yale Univ, Dept Gynecol Oncol, New Haven, CT USA. [Uduman, Mohamed] Yale Univ, Interdept Program Computat Biol & Bioinformat, New Haven, CT USA. [Winter, Kathryn] RTOG, Ctr Stat, Philadelphia, PA USA. [Greven, Kathryn M.] Wake Forest Univ, Baptist Med Ctr, Dept Radiat Oncol, Winston Salem, NC 27109 USA. [King, Stephanie] Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. [Burke, Thomas W.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Underhill, Kelly] Benefis Sletten Canc Inst, Dept Radiat Oncol, Great Falls, MT USA. [Kim, Harold] Wayne State Univ, Dept Radiat Oncol, Karamanos Canc Ctr, Detroit, MI 48202 USA. [Boulware, Raleigh J.] South Carolina Oncol Associates, Radiat Oncol, Columbia, SC USA. [Dicker, Adam P.] Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Philadelphia, PA 19107 USA. [Yu, Herbert; Lu, Lingeng] Yale Univ, Dept Chron Dis & Epidemiol, New Haven, CT USA. [Yu, Herbert] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA. [Weidhaas, Joanne] Yale Univ, Dept Therapeut Radiol, New Haven, CT 06520 USA. [Gaffney, David] Univ Utah, Huntsman Canc Hosp, Dept Radiat Oncol, Salt Lake City, UT USA. [Parkash, Vinita] Yale Univ, Dept Pathol, New Haven, CT USA. RP Weidhaas, J (reprint author), Yale Univ, Dept Therapeut Radiol, New Haven, CT 06520 USA. EM joanne.weidhaas@yale.edu OI Weidhaas, Joanne/0000-0002-5096-3281; Dicker, Adam/0000-0003-0733-3337 FU NCI-NIH [5R01CA098346]; Radiation Therapy Oncology Group/American College of Radiology (RTOG/ACR) Fellowship Program; National Cancer Institute (NCI) [U10 CA21661, U10 CA37422]; [R01 CA131301-04]; [CA-157749-01A15]; [5R01CA131301-05] FX This study was supported by NCI-NIH grant 5R01CA098346. This research was also supported by Radiation Therapy Oncology Group/American College of Radiology (RTOG/ACR) Fellowship Program and RTOG grants U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI) and by NCI-NIH grant 5R01CA098346. JW was supported by R01 CA131301-04, CA-157749-01A15 and 5R01CA131301-05. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 5 Z9 5 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 14 PY 2014 VL 9 IS 4 AR e94167 DI 10.1371/journal.pone.0094167 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI6GP UT WOS:000336970400022 PM 24732316 ER PT J AU Tan, XJ Fuchs, BB Wang, Y Chen, WP Yuen, GJ Chen, RB Jayamani, E Anastassopoulou, C Pukkila-Worley, R Coleman, JJ Mylonakis, E AF Tan, Xiaojiang Fuchs, Beth Burgwyn Wang, Yan Chen, Weiping Yuen, Grace J. Chen, Rosalyn B. Jayamani, Elamparithi Anastassopoulou, Cleo Pukkila-Worley, Read Coleman, Jeffrey J. Mylonakis, Eleftherios TI The Role of Candida albicans SPT20 in Filamentation, Biofilm Formation and Pathogenesis SO PLOS ONE LA English DT Article ID CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATION; SIGNALING SPECIFICITY; GALLERIA-MELLONELLA; HYPHAL FORMATION; BINDING PROTEIN; SAGA COMPLEX; HISTONE H2B; IN-VIVO AB Candida albicans is a ubiquitous fungus, which can cause very serious and sometimes life-threatening infections in susceptible patients. We used Caenorhabditis elegans as a model host to screen a library of C. albicans mutants for decreased virulence and identified SPT20 as important for virulence. The transcription co-activator SPT20 was identified originally as a suppressor of Ty and solo delta insertion mutations, which can cause transcription defects in Saccharomyces cerevisiae. It is resistant to the toxicity caused by overexpression of GAL4-VP16. We constructed a C. albicans spt20 Delta/Delta mutant and found the spt20 Delta/Delta strain was significantly less virulent than the wild-type strain SC5314 in C. elegans (p < 0.0001), Galleria mellonella (p < 0.01) and mice (p < 0.001). Morphologically, spt20 Delta/Delta mutant cells demonstrated a "snow-flake'' shape and clustered together; prolonged culture times resulted in increased size of the cluster. The clustered morphology was associated with defects in nuclei distribution, as the nuclei were not observed in many cellular compartments. In addition, the C. albicans spt20 Delta/Delta mutant resulted in defects in hyphae and biofilm formation (compared to the wild-type strain, p < 0.05), and sensitivity to cell wall and osmotic stressors, and to antifungal agents. Thus our study demonstrated a role of C. albicans SPT20 in overall morphology and distribution of nuclear material, which may cause the defects in filamentation and biofilm formation directly when this gene is deleted. C1 [Tan, Xiaojiang; Chen, Weiping] Southern Med Univ, Nanfang Hosp, Overseas Med Ctr, Dept Respirat, Guangzhou, Guangdong, Peoples R China. [Tan, Xiaojiang; Fuchs, Beth Burgwyn; Jayamani, Elamparithi; Coleman, Jeffrey J.; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Med,Infect Dis Div, Providence, RI 02903 USA. [Tan, Xiaojiang; Fuchs, Beth Burgwyn; Wang, Yan; Anastassopoulou, Cleo; Pukkila-Worley, Read; Coleman, Jeffrey J.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Wang, Yan] Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China. [Yuen, Grace J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. [Yuen, Grace J.] Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. [Chen, Rosalyn B.] Phillips Acad, Andover, MA USA. RP Tan, XJ (reprint author), Southern Med Univ, Nanfang Hosp, Overseas Med Ctr, Dept Respirat, Guangzhou, Guangdong, Peoples R China. EM nfyytxj@gmail.com; emylonakis@lifespan.org RI Coleman, Jeffrey/E-2981-2015; OI Coleman, Jeffrey/0000-0001-8579-1996 FU National Institutes of Health [AI075286, AI070569]; Science and Technology Planning Project of Guangdong Province, P.R. China [2011B080701091] FX This work was supported by the National Institutes of Health through an R01 award (AI075286), and an R21 award (AI070569) to Eleftherios Mylonakis, and Science and Technology Planning Project of Guangdong Province, P.R. China (2011B080701091) to Xiaojiang Tan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 4 Z9 6 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 14 PY 2014 VL 9 IS 4 AR e94468 DI 10.1371/journal.pone.0094468 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI6GP UT WOS:000336970400040 PM 24732310 ER PT J AU Phillips, CM Montgomery, BE Breen, PC Roovers, EF Rim, YS Ohsumi, TK Newman, MA van Wolfswinkel, JC Ketting, RF Ruvkun, G Montgomery, TA AF Phillips, Carolyn M. Montgomery, Brooke E. Breen, Peter C. Roovers, Elke F. Rim, Young-Soo Ohsumi, Toshiro K. Newman, Martin A. van Wolfswinkel, Josien C. Ketting, Rene F. Ruvkun, Gary Montgomery, Taiowa A. TI MUT-14 and SMUT-1 DEAD Box RNA Helicases Have Overlapping Roles in Germline RNAi and Endogenous siRNA Formation SO CURRENT BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; C.-ELEGANS; CHROMOSOME SEGREGATION; FRAMEWORK AB More than 2,000 C. elegans genes are targeted for RNA silencing by the mutator complex, a specialized small interfering RNA (siRNA) amplification module which is nucleated by the Q/N-rich protein MUT-16. The mutator complex localizes to Mutator foci adjacent to P granules at the nuclear periphery in germ cells [1]. Here, we show that the DEAD box RNA helicase smut-1 functions redundantly in the mutator pathway with its paralog mut-14 during RNAi. Mutations in both smut-1 and mut-14 also cause widespread loss of endogenous siRNAs. The targets of mut-14 and smut-1 largely overlap with the targets of other mutator class genes; however, the mut-14 smut-1 double mutant and the mut-16 mutant display the most dramatic depletion of siRNAs, suggesting that they act at a similarly early step in siRNA formation. mut-14 and smut-1 are predominantly expressed in the germline and, unlike other mutator class genes, are specifically required for RNAi targeting germline genes. A catalytically inactive, dominant-negative missense mutant of MUT-14 is RNAi defective in vivo; however, mutator complexes containing the mutant protein retain the ability to synthesize siRNAs in vitro. The results point to a role for mut-14 and smut-1 in initiating siRNA amplification in germ cell Mutator foci, possibly through the recruitment or retention of target mRNAs. C1 [Phillips, Carolyn M.; Breen, Peter C.; Rim, Young-Soo; Ohsumi, Toshiro K.; Newman, Martin A.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Phillips, Carolyn M.; Breen, Peter C.; Rim, Young-Soo; Ohsumi, Toshiro K.; Newman, Martin A.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Montgomery, Brooke E.; Montgomery, Taiowa A.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Roovers, Elke F.; Ketting, Rene F.] Inst Mol Biol, D-55128 Mainz, Germany. [van Wolfswinkel, Josien C.; Ketting, Rene F.] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands. [van Wolfswinkel, Josien C.; Ketting, Rene F.] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu; tai.montgomery@colostate.edu RI Phillips, Carolyn/E-8305-2011; OI Phillips, Carolyn/0000-0002-6228-6468; Montgomery, Taiowa/0000-0001-7857-3253 FU NIH Office of Research Infrastructure Programs [P40 OD010440]; Shohei Mitani of the Japanese National Bioresources Project; European Community; CNRS; NIH [GM44619]; Colorado State University; Massachusetts General Hospital Executive Committee of Research; Damon Runyon Cancer Research Foundation; ERC from the Ideas Program of the European Union Seventh Framework Program [202819] FX Thanks to Ulandt Kim and Yanqun Wang for Illumina sequencing. Strains were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), and Shohei Mitani of the Japanese National Bioresources Project. Mos strains were generated by the Ewbank and Segalat labs as part of the NEMAGENETAG project funded by the European Community and distributed by M. Carre-Pierrat at the UMS 3421, supported by the CNRS. This work was supported by the NIH (GM44619 to G.R.), Colorado State University (T.A.M.), the Massachusetts General Hospital Executive Committee of Research (C.M.P. and T.A.M.), the Damon Runyon Cancer Research Foundation (C.M.P. and T.A.M.), and an ERC Starting Grant (202819) from the Ideas Program of the European Union Seventh Framework Program (R.F.K.). NR 20 TC 8 Z9 8 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD APR 14 PY 2014 VL 24 IS 8 BP 839 EP 844 DI 10.1016/j.cub.2014.02.060 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AE8SQ UT WOS:000334272700019 PM 24684932 ER PT J AU Castellanos-Rizaldos, E Milbury, CA Karatza, E Chen, CC Makrigiorgos, GM Merewood, A AF Castellanos-Rizaldos, Elena Milbury, Coren A. Karatza, Elli Chen, Clark C. Makrigiorgos, G. Mike Merewood, Anne TI COLD-PCR Amplification of Bisulfite-Converted DNA Allows the Enrichment and Sequencing of Rare Un-Methylated Genomic Regions SO PLOS ONE LA English DT Article ID RESOLUTION MELTING ANALYSIS; PROMOTER METHYLATION; MUTATION DETECTION; CANCER; SENSITIVITY; ASSAY; IDENTIFICATION; GLIOBLASTOMA; KRAS AB Aberrant hypo-methylation of DNA is evident in a range of human diseases including cancer and diabetes. Development of sensitive assays capable of detecting traces of un-methylated DNA within methylated samples can be useful in several situations. Here we describe a new approach, fast-COLD-MS-PCR, which amplifies preferentially un-methylated DNA sequences. By employing an appropriate denaturation temperature during PCR of bi-sulfite converted DNA, fast-COLD-MS-PCR enriches un-methylated DNA and enables differential melting analysis or bisulfite sequencing. Using methylation on the MGMT gene promoter as a model, it is shown that serial dilutions of controlled methylation samples lead to the reliable sequencing of un-methylated sequences down to 0.05% un-methylated-to-methylated DNA. Screening of clinical glioma tumor and infant blood samples demonstrated that the degree of enrichment of un-methylated over methylated DNA can be modulated by the choice of denaturation temperature, providing a convenient method for analysis of partially methylated DNA or for revealing and sequencing traces of un-methylated DNA. Fast-COLD-MS-PCR can be useful for the detection of loss of methylation/imprinting in cancer, diabetes or diet-related methylation changes. C1 [Castellanos-Rizaldos, Elena; Milbury, Coren A.; Karatza, Elli; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, San Diego, CA 92103 USA. [Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Phys & Biophys,Dept Radiat Oncol,Brigham, Boston, MA 02115 USA. [Merewood, Anne] Boston Med Ctr, Div Gen Pediat, Boston, MA USA. [Merewood, Anne] Boston Univ, Boston, MA 02215 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu FU NCI [1R03CA139406, R21CA-155615, R21CA-175542] FX This work was supported by NCI grants 1R03CA139406 (AM); R21CA-155615 and R21CA-175542 (GMM). The contents of this manuscript do not necessarily represent the official views of the National Cancer Institute 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 27 TC 3 Z9 5 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2014 VL 9 IS 4 AR e94103 DI 10.1371/journal.pone.0094103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3CI UT WOS:000336736200037 PM 24728321 ER PT J AU Coroller, TP Mak, RH Lewis, JH Baldini, EH Chen, AB Colson, YL Hacker, FL Hermann, G Kozono, D Mannarino, E Molodowitch, C Wee, JO Sher, DJ Killoran, JH AF Coroller, Thibaud P. Mak, Raymond H. Lewis, John H. Baldini, Elizabeth H. Chen, Aileen B. Colson, Yolonda L. Hacker, Fred L. Hermann, Gretchen Kozono, David Mannarino, Edward Molodowitch, Christina Wee, Jon O. Sher, David J. Killoran, Joseph H. TI Low Incidence of Chest Wall Pain with a Risk-Adapted Lung Stereotactic Body Radiation Therapy Approach Using Three or Five Fractions Based on Chest Wall Dosimetry SO PLOS ONE LA English DT Article ID PHASE-II; CANCER; RADIOTHERAPY; IRRADIATION; TOXICITY; OUTCOMES AB Purpose: To examine the frequency and potential of dose-volume predictors for chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung stereotactic body radiotherapy (SBRT) using treatment planning methods to minimize CW dose and a risk-adapted fractionation scheme. Methods: We reviewed data from 72 treatment plans, from 69 lung SBRT patients with at least one year of follow-up or CW toxicity, who were treated at our center between 2010 and 2013. Treatment plans were optimized to reduce CW dose and patients received a risk-adapted fractionation of 18 Gyx3 fractions (54 Gy total) if the CW V30 was less than 30 mL or 1012 Gyx5 fractions (50-60 Gy total) otherwise. The association between CW toxicity and patient characteristics, treatment parameters and dose metrics, including biologically equivalent dose, were analyzed using logistic regression. Results: With a median follow-up of 20 months, 6 (8.3%) patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which was symptomatic. No significant associations between CW toxicity and patient and dosimetric variables were identified on univariate nor multivariate analysis. Conclusions: Optimization of treatment plans to reduce CW dose and a risk-adapted fractionation strategy of three or five fractions based on the CW V30 resulted in a low incidence of CW toxicity. Under these conditions, none of the patient characteristics or dose metrics we examined appeared to be predictive of CW pain. C1 [Coroller, Thibaud P.; Mak, Raymond H.; Lewis, John H.; Baldini, Elizabeth H.; Chen, Aileen B.; Hacker, Fred L.; Hermann, Gretchen; Kozono, David; Mannarino, Edward; Molodowitch, Christina; Killoran, Joseph H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Coroller, Thibaud P.; Mak, Raymond H.; Lewis, John H.; Baldini, Elizabeth H.; Chen, Aileen B.; Colson, Yolonda L.; Hacker, Fred L.; Kozono, David; Wee, Jon O.; Killoran, Joseph H.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Colson, Yolonda L.; Wee, Jon O.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. [Sher, David J.] Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. [Coroller, Thibaud P.] Univ Grenoble 1, Dept Engn Hlth & Med, Grenoble, France. RP Killoran, JH (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM jkilloran@lroc.harvard.edu OI Coroller, Thibaud/0000-0001-7662-8724 FU Kayes Family Scholars Award FX This study was supported by a Kayes Family Scholars Award, an internal grant specific to the authors' department. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 19 TC 9 Z9 9 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2014 VL 9 IS 4 AR e94859 DI 10.1371/journal.pone.0094859 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3CI UT WOS:000336736200136 PM 24728448 ER PT J AU Hammerling, D Cefalu, M Cisewski, J Dominici, F Parmigiani, G Paulson, C Smith, RL AF Hammerling, Dorit Cefalu, Matthew Cisewski, Jessi Dominici, Francesca Parmigiani, Giovanni Paulson, Charles Smith, Richard L. TI Completing the Results of the 2013 Boston Marathon SO PLOS ONE LA English DT Article AB The 2013 Boston marathon was disrupted by two bombs placed near the finish line. The bombs resulted in three deaths and several hundred injuries. Of lesser concern, in the immediate aftermath, was the fact that nearly 6,000 runners failed to finish the race. We were approached by the marathon's organizers, the Boston Athletic Association (BAA), and asked to recommend a procedure for projecting finish times for the runners who could not complete the race. With assistance from the BAA, we created a dataset consisting of all the runners in the 2013 race who reached the halfway point but failed to finish, as well as all runners from the 2010 and 2011 Boston marathons. The data consist of split times from each of the 5 km sections of the course, as well as the final 2.2 km (from 40 km to the finish). The statistical objective is to predict the missing split times for the runners who failed to finish in 2013. We set this problem in the context of the matrix completion problem, examples of which include imputing missing data in DNA microarray experiments, and the Netflix prize problem. We propose five prediction methods and create a validation dataset to measure their performance by mean squared error and other measures. The best method used local regression based on a K-nearest-neighbors algorithm (KNN method), though several other methods produced results of similar quality. We show how the results were used to create projected times for the 2013 runners and discuss potential for future application of the same methodology. We present the whole project as an example of reproducible research, in that we are able to make the full data and all the algorithms we have used publicly available, which may facilitate future research extending the methods or proposing completely different approaches. C1 [Hammerling, Dorit; Smith, Richard L.] Stat & Appl Math Sci Inst, Res Triangle Pk, NC 27709 USA. [Cefalu, Matthew; Dominici, Francesca; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Cisewski, Jessi] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paulson, Charles] Puffinware LLC, State Coll, PA USA. [Smith, Richard L.] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC USA. RP Smith, RL (reprint author), Stat & Appl Math Sci Inst, Res Triangle Pk, NC 27709 USA. EM rls@email.unc.edu OI Hammerling, Dorit/0000-0003-3583-3611 FU National Science Foundation [DMS-1127914, DMS-1043903] FX Dorit Hammerling and Richard Smith were partially supported by the National Science Foundation under Grant DMS-1127914 to the Statistical and Applied Mathematical Sciences Institute, and Jessi Cisewski was partially supported by the National Science Foundation under Grant DMS-1043903. The National Science Foundation had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 7 TC 1 Z9 1 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2014 VL 9 IS 4 AR e93800 DI 10.1371/journal.pone.0093800 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3CI UT WOS:000336736200027 PM 24727904 ER PT J AU Peter, PR Park, KH Huh, JY Wedick, NM Mantzoros, CS AF Peter, Patricia R. Park, Kyung Hee Huh, Joo Young Wedick, Nicole M. Mantzoros, Christos S. TI Circulating Irisin Levels Are Not Affected by Coffee Intake: A Randomized Controlled Trial SO PLOS ONE LA English DT Article ID SKELETAL-MUSCLE; BROWN-FAT; OBESITY; HUMANS; CONSUMPTION; MYOKINE; WEIGHT; PLASMA; COHORT; WOMEN AB Irisin, secreted by skeletal muscle and possibly fat, is hypothesized to play an important role in modulating energy expenditure, obesity and metabolism. Coffee consumption also increases energy expenditure and leads to positive metabolic effects, but whether these effects are mediated by irisin remains unknown. The objective of this study was to determine the association between baseline irisin levels and the metabolic profile in humans and to investigate whether consumption of caffeinated coffee alters irisin levels. To this end, a secondary analysis was performed investigating irisin levels at baseline and after eight weeks in 32 healthy, overweight coffee drinkers who were randomized to consumption of 5 cups per day of instant caffeinated coffee, decaffeinated coffee, or water. Spearman correlation and analysis of covariance analyses were performed to identify possible associations. Irisin levels were positively correlated with waist circumference (r = 0.41, p = 0.02), fat mass (r = 0.44, p = 0.01) and CRP (r = 0.47, p = 0.007). Though there was a trend towards increased levels of irisin over time in the caffeinated coffee group (+ 1.8%) when compared to the placebo group (-4%) this did not reach statistical significance (p = 0.75 for the trend). This first randomized trial failed to reveal any effects of coffee consumption on irisin levels, but a larger trial, appropriately sized on the basis of data provided by this study, is needed to conclusively investigate such a relationship. C1 [Peter, Patricia R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Internal Med, Boston, MA 02215 USA. [Park, Kyung Hee; Huh, Joo Young; 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, South Korea. [Wedick, Nicole M.] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu OI Park, Kyung Hee/0000-0001-9806-0076 FU National Institute of Diabetes and Digestive and Kidney Diseases [81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant 81913 and by the Clinical Science Research and Development Service of the VA Office of Research and Development grant 1I01CX000422-01A1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 8 Z9 8 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 11 PY 2014 VL 9 IS 4 AR e94463 DI 10.1371/journal.pone.0094463 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI3CI UT WOS:000336736200077 PM 24728416 ER PT J AU Goetzman, ES Alcorn, JF Bharathi, SS Uppala, R McHugh, KJ Kosmider, B Chen, RM Zuo, YY Beck, ME McKinney, RW Skilling, H Suhrie, KR Karunanidhi, A Yeasted, R Otsubo, C Ellis, B Tyurina, YY Kagan, VE Mallampalli, RK Vockley, J AF Goetzman, Eric S. Alcorn, John F. Bharathi, Sivakama S. Uppala, Radha McHugh, Kevin J. Kosmider, Beata Chen, Rimei Zuo, Yi Y. Beck, Megan E. McKinney, Richard W. Skilling, Helen Suhrie, Kristen R. Karunanidhi, Anuradha Yeasted, Renita Otsubo, Chikara Ellis, Bryon Tyurina, Yulia Y. Kagan, Valerian E. Mallampalli, Rama K. Vockley, Jerry TI Long-chain Acyl-CoA Dehydrogenase Deficiency as a Cause of Pulmonary Surfactant Dysfunction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Fatty Acid Oxidation; Genetic Diseases; Lung; Mitochondrial Metabolism; Pulmonary Surfactant; Acyl-CoA Dehydrogenase ID ACID BETA-OXIDATION; ORGANIC CATION/CARNITINE TRANSPORTER; RESPIRATORY-DISTRESS-SYNDROME; ALVEOLAR EPITHELIAL-CELLS; CAPTIVE BUBBLE METHOD; FREE CARNITINE LEVELS; INFLUENZA-A VIRUS; LUNG SURFACTANT; IN-VITRO; COMPLEX I AB Background: The contribution of long-chain acyl-CoA dehydrogenase (LCAD) to human fatty acid oxidation is not understood. Results: LCAD localizes to lung alveolar type II cells, which produce pulmonary surfactant; LCAD-deficient mice have surfactant dysfunction. Conclusion: LCAD is important for lung energy metabolism and lung function. Significance: LCAD may play a role in human lung disease and unexplained sudden infant death. Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial fatty acid oxidation enzyme whose expression in humans is low or absent in organs known to utilize fatty acids for energy such as heart, muscle, and liver. This study demonstrates localization of LCAD to human alveolar type II pneumocytes, which synthesize and secrete pulmonary surfactant. The physiological role of LCAD and the fatty acid oxidation pathway in lung was subsequently studied using LCAD knock-out mice. Lung fatty acid oxidation was reduced in LCAD(-/-) mice. LCAD(-/-) mice demonstrated reduced pulmonary compliance, but histological examination of lung tissue revealed no obvious signs of inflammation or pathology. The changes in lung mechanics were found to be due to pulmonary surfactant dysfunction. Large aggregate surfactant isolated from LCAD(-/-) mouse lavage fluid had significantly reduced phospholipid content as well as alterations in the acyl chain composition of phosphatidylcholine and phosphatidylglycerol. LCAD(-/-) surfactant demonstrated functional abnormalities when subjected to dynamic compression-expansion cycling on a constrained drop surfactometer. Serum albumin, which has been shown to degrade and inactivate pulmonary surfactant, was significantly increased in LCAD(-/-) lavage fluid, suggesting increased epithelial permeability. Finally, we identified two cases of sudden unexplained infant death where no lung LCAD antigen was detectable. Both infants were homozygous for an amino acid changing polymorphism (K333Q). These findings for the first time identify the fatty acid oxidation pathway and LCAD in particular as factors contributing to the pathophysiology of pulmonary disease. C1 [Goetzman, Eric S.; Alcorn, John F.; Bharathi, Sivakama S.; Uppala, Radha; McHugh, Kevin J.; McKinney, Richard W.; Skilling, Helen; Suhrie, Kristen R.; Karunanidhi, Anuradha; Yeasted, Renita; Otsubo, Chikara; Vockley, Jerry] Univ Pittsburgh Sch Med, Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15224 USA. [Goetzman, Eric S.; Beck, Megan E.; Vockley, Jerry] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15213 USA. [Kosmider, Beata] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Chen, Rimei; Zuo, Yi Y.] Univ Hawaii Manoa, Dept Mech Engn, Honolulu, HI 96822 USA. [Ellis, Bryon; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Tyurina, Yulia Y.; Kagan, Valerian E.] Univ Pittsburgh, Ctr Free Radical & Antioxidant Hlth, Pittsburgh, PA 15260 USA. [Tyurina, Yulia Y.; Kagan, Valerian E.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15213 USA. RP Goetzman, ES (reprint author), 4401 Penn Ave,Rangos 5117, Pittsburgh, PA 15224 USA. EM eric.goetzman@chp.edu OI Vockley, Jerry/0000-0002-8180-6457 FU National Institutes of Health [DK090242]; NIDDK [DK78775]; NHLBI [HL107380, HL096376, HL097376, HL098174, P01 HL114453] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK090242 (to E. S. G.) and DK78775 (to J. V.) from NIDDK and Grants HL107380 (to J. F. A.), HL096376, HL097376, and HL098174 (to R. K. M.), P01 HL114453 (to R. K. M. and V. E. K.) from NHLBI. NR 69 TC 8 Z9 8 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 11 PY 2014 VL 289 IS 15 BP 10668 EP 10679 DI 10.1074/jbc.M113.540260 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AE8CI UT WOS:000334226400037 PM 24591516 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Depression in primary TKA and higher medical comorbidities in revision TKA are associated with suboptimal subjective improvement in knee function SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article DE Total knee arthroplasty; Knee function; Functional limitation; Primary; Arthroplasty; Joint replacement; Outcomes; Patient-reported outcomes ID QUALITY-OF-LIFE; TOTAL HIP; REPLACEMENT SURGERY; JOINT REPLACEMENT; PAIN MEDICATIONS; UNITED-STATES; POOR PAIN; ARTHROPLASTY; OUTCOMES; PREDICTORS AB Background: To characterize whether medical comorbidities, depression and anxiety predict patient-reported functional improvement after total knee arthroplasty (TKA). Methods: We analyzed the prospectively collected data from the Mayo Clinic Total Joint Registry for patients who underwent primary or revision TKA between 1993-2005. Using multivariable-adjusted logistic regression analyses, we examined whether medical comorbidities, depression and anxiety were associated with patient-reported subjective improvement in knee function 2- or 5-years after primary or revision TKA. Odds ratios (OR), along with 95% confidence intervals (CI) and p-value are presented. Results: We studied 7,139 primary TKAs at 2- and 4,234 at 5-years; and, 1,533 revision TKAs at 2-years and 881 at 5-years. In multivariable-adjusted analyses, we found that depression was associated with significantly lower odds of 0.5 (95% confidence interval [CI]: 0.3 to 0.9; p = 0.02) of 'much better' knee functional status (relative to same or worse status) 2 years after primary TKA. Higher Deyo-Charlson index was significantly associated with lower odds of 0.5 (95% CI: 0.2 to 1.0; p = 0.05) of 'much better' knee functional status after revision TKA for every 5-point increase in score. Conclusions: Depression in primary TKA and higher medical comorbidity in revision TKA cohorts were associated with suboptimal improvement in index knee function. It remains to be seen whether strategies focused at optimization of medical comorbidities and depression pre- and peri-operatively may help to improve TKA outcomes. Study limitations include non-response bias and the use of diagnostic codes, which may be associated with under-diagnosis of conditions. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 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 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. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM Jasvinder.md@gmail.coml FU Mayo Clinic Orthopedic Surgery; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institute of Aging (NIA); National Cancer Institute (NCI) FX This material is the result of work supported with research grants from the Mayo Clinic Orthopedic Surgery research funds and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute of Aging (NIA) and National Cancer Institute (NCI). NR 51 TC 15 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD APR 11 PY 2014 VL 15 AR 127 DI 10.1186/1471-2474-15-127 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AG1PZ UT WOS:000335189300004 PM 24725511 ER PT J AU Groschel, S Sanders, MA Hoogenboezem, R de Wit, E Bouwman, BAM Erpelinck, C van der Velden, VHJ Havermans, M Avellino, R van Lom, K Rombouts, EJ van Duin, M Dohner, K Beverloo, HB Bradner, JE Dohner, H Lowenberg, B Valk, PJM Bindels, EMJ de Laat, W Delwel, R AF Groeschel, Stefan Sanders, Mathijs A. Hoogenboezem, Remco de Wit, Elzo Bouwman, Britta A. M. Erpelinck, Claudia van der Velden, Vincent H. J. Havermans, Marije Avellino, Roberto van Lom, Kirsten Rombouts, Elwin J. van Duin, Mark Doehner, Konstanze Beverloo, H. Berna Bradner, James E. Doehner, Hartmut Lowenberg, Bob Valk, Peter J. M. Bindels, Eric M. J. de Laat, Wouter Delwel, Ruud TI A Single Oncogenic Enhancer Rearrangement Causes Concomitant EVI1 and GATA2 Deregulation in Leukemia SO CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; MONOMAC SYNDROME; SUPER-ENHANCERS; HUMAN GENOME; LOCUS; MUTATIONS; ACTIVATION; HAPLOINSUFFICIENCY; ABNORMALITIES AB Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional genomics and genome-engineering, we demonstrate that both 3q rearrangements reposition a distal GATA2 enhancer to ectopically activate EVI1 and simultaneously confer GATA2 functional haploinsufficiency, previously identified as the cause of sporadic familial AML/MDS and MonoMac/Emberger syndromes. Genomic excision of the ectopic enhancer restored EVI1 silencing and led to growth inhibition and differentiation of AML cells, which could be replicated by pharmacologic BET inhibition. Our data show that structural rearrangements involving the chromosomal repositioning of a single enhancer can cause deregulation of two unrelated distal genes, with cancer as the outcome. C1 [Groeschel, Stefan; Sanders, Mathijs A.; Hoogenboezem, Remco; Erpelinck, Claudia; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J.; van Duin, Mark; Lowenberg, Bob; Valk, Peter J. M.; Bindels, Eric M. J.; Delwel, Ruud] Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 GE Rotterdam, Netherlands. [Groeschel, Stefan; Doehner, Konstanze; Doehner, Hartmut] Ulm Univ Hosp, Dept Internal Med 2, D-89081 Ulm, Germany. [de Wit, Elzo; Bouwman, Britta A. M.; de Laat, Wouter] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands. [de Wit, Elzo; Bouwman, Britta A. M.; de Laat, Wouter] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. [van der Velden, Vincent H. J.] Erasmus Univ, Med Ctr, Dept Immunol, NL-3015 CN Rotterdam, Netherlands. [Beverloo, H. Berna] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands. [Beverloo, H. Berna] Dutch Working Grp Hematooncol Genome Diagnost, NL-3015 GE Rotterdam, Netherlands. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Delwel, R (reprint author), Erasmus Univ, Med Ctr, Dept Hematol, NL-3015 GE Rotterdam, Netherlands. EM h.delwel@erasmusmc.nl OI de Wit, Elzo/0000-0003-2883-1415 FU Deutsche Forschungsgemeinschaft [GR 3955/1-1]; Lady Tata Memorial Trust; Association for International Cancer Research; Center for Translational Molecular Medicine (CTMM) [GR03O-102]; EHA Research Fellowship FX We thank J. Qi for providing JQ1; I. P. Touw, P. van Strien, K. Eiwen, J. van Galen, A. C. Bijkerk, P. Hogenbirk-Hupkes, J. Koenders, F. Cornelissen, H. van de Werken, and other members of the Department of Hematology at the Erasmus MC for their support; E. Simons for editorial assistance. We thank L. Cong and F. Zhang from the Broad Institute for their support with the CRISPR/Cas9 toolbox. This work was financially supported by grants from the Deutsche Forschungsgemeinschaft (GR 3955/1-1, S. Groschel), the Lady Tata Memorial Trust, Association for International Cancer Research (E. Bindels), the Center for Translational Molecular Medicine (CTMM; GR03O-102, M. Sanders) and an EHA Research Fellowship (S. Groschel). NR 35 TC 107 Z9 110 U1 4 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 10 PY 2014 VL 157 IS 2 BP 369 EP 381 DI 10.1016/j.cell.2014.02.019 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AE9DK UT WOS:000334304500011 PM 24703711 ER PT J AU Schnell, E Long, TH Bensen, AL Washbum, EK Westbrook, GL AF Schnell, Eric Long, Thomas H. Bensen, AeSoon L. Washbum, Eric K. Westbrook, Gary L. TI Neuroligin-1 knockdown reduces survival of adult-generated newborn hippocampal neurons SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE adult neurogenesis; neuroligin-1; cell survival; dendritic spine; synaptogenesis; dendritic growth ID TERM SYNAPTIC PLASTICITY; DENTATE GYRUS; NEUROGENESIS; SYNAPTOGENESIS; INTEGRATION; MATURATION; DOMAIN; CELLS; RAC1; MICE AB Survival of adult-born hippocampal granule cells is modulated by neural activity, and thought to be enhanced by excitatory synaptic signaling. Here, we report that a reduction in the synaptogenic protein neuroligin-1 in adult-born neurons in vivo decreased their survival, but surprisingly, this effect was independent of changes in excitatory synaptic function. Instead, the decreased survival was associated with unexpected changes in dendrite and spine morphology during granule cell maturation, suggesting a link between cell growth and survival. C1 [Schnell, Eric] Portland VA Med Ctr, Portland, OR 97239 USA. [Schnell, Eric] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Long, Thomas H.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Bensen, AeSoon L.; Washbum, Eric K.; Westbrook, Gary L.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. RP Schnell, E (reprint author), Portland VA Med Ctr, P3ANES,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM schneler@ohsu.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development CDA-2 award [NIH NS26494, MH046613, UL1TR000128, P30NS061800] FX We thank Stefanie Kaech-Petrie for imaging assistance, Ken Tovar for comments on the manuscript, Bryan Luikart for his work in constructing and optimizing viral vectors, and Laura Villasana for assistance in blinding. This material was supported in part by a Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development CDA-2 award (Eric Schnell) and NIH NS26494 (Gary L. Westbrook), MH046613 (Gary L. Westbrook), UL1TR000128 (Thomas H. Long), and P30NS061800 (OHSU) awards. NR 36 TC 6 Z9 6 U1 1 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD APR 10 PY 2014 VL 8 AR 71 DI 10.3389/fnins.2014.00071 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AW7SD UT WOS:000346463800001 PM 24782702 ER PT J AU Baxt, LA Goldberg, MB AF Baxt, Leigh A. Goldberg, Marcia B. TI Host and Bacterial Proteins That Repress Recruitment of LC3 to Shigella Early during Infection SO PLOS ONE LA English DT Article ID ACTIN-BASED MOTILITY; N-WASP; ANTIBACTERIAL AUTOPHAGY; LISTERIA-MONOCYTOGENES; ESCHERICHIA-COLI; CELL LINES; HELA-CELLS; FLEXNERI; PATHOGENS; PHAGOCYTOSIS AB Shigella spp. are intracytosolic gram-negative pathogens that cause disease by invasion and spread through the colonic mucosa, utilizing host cytoskeletal components to form propulsive actin tails. We have previously identified the host factor Toca-1 as being recruited to intracellular S. flexneri and being required for efficient bacterial actin tail formation. We show that at early times during infection (40 min.), the type three-secreted effector protein IcsB recruits Toca-1 to intracellular bacteria and that recruitment of Toca-1 is associated with repression of recruitment of LC3, as well as with repression of recruitment of the autophagy marker NDP52, around these intracellular bacteria. LC3 is best characterized as a marker of autophagosomes, but also marks phagosomal membranes in the process LC3-associated phagocytosis. IcsB has previously been demonstrated to be required for S. flexneri evasion of autophagy at late times during infection (4-6 hr) by inhibiting binding of the autophagy protein Atg5 to the Shigella surface protein IcsA (VirG). Our results suggest that IcsB and Toca-1 modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants. Together with published results, our findings suggest that IcsB inhibits innate immune responses in two distinct ways, first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants early during infection, and second, by inhibiting autophagy late during infection. C1 [Baxt, Leigh A.; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Cambridge, MA USA. [Baxt, Leigh A.; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Cambridge, MA USA. EM marcia.goldberg@mgh.harvard.edu FU National Institutes of Health (NIH) [R01 AI081724, R21 AI083624, F32 AI092967] FX This work has been supported by National Institutes of Health (NIH) R01 AI081724 (to MBG), NIH R21 AI083624 (to MBG) and NIH F32 AI092967 (to LAB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 19 Z9 19 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 APR 10 PY 2014 VL 9 IS 4 AR e94653 DI 10.1371/journal.pone.0094653 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5LS UT WOS:000336909100117 PM 24722587 ER PT J AU Chang, H Yanachkov, IB Dix, EJ Yanachkova, M Li, YF Barnard, MR Wright, GE Michelson, AD Frelinger, AL AF Chang, Hung Yanachkov, Ivan B. Dix, Edward J. Yanachkova, Milka Li, YouFu Barnard, Marc R. Wright, George E. Michelson, Alan D. Frelinger, Andrew L., III TI Antiplatelet Activity, P2Y(1) and P2Y(12) Inhibition, and Metabolism in Plasma of Stereoisomers of Diadenosine 5 ',5 '''-P-1, P-4-dithio-P-2,P-3-chloromethylenetetraphosphate SO PLOS ONE LA English DT Article ID PLATELET-AGGREGATION; PURINERGIC RECEPTORS; MICROPLATE READER; POLYPHOSPHATES; ADP; DIASTEREOSELECTIVITY; OLIGONUCLEOTIDES; RECOGNITION; ANTAGONISTS; ANALOGS AB Background: Diadenosine tetraphosphate (Ap(4)A), a constituent of platelet dense granules, and its P-1, P-4-dithio and/or P-2, P-3-chloromethylene analogs, inhibit adenosine diphosphate (ADP)-induced platelet aggregation. We recently reported that these compounds antagonize both platelet ADP receptors, P2Y(1) and P2Y(12). The most active of those analogs, diadenosine 5',5''''-P-1, P-4-dithio-P-2, P-3-chloromethylenetetraphosphate, (compound 1), exists as a mixture of 4 stereoisomers. Objective: To separate the stereoisomers of compound 1 and determine their effects on platelet aggregation, platelet P2Y1 and P2Y12 receptor antagonism, and their metabolism in human plasma. Methods: We separated the 4 diastereomers of compound 1 by preparative reversed-phase chromatography, and studied their effect on ADP-induced platelet aggregation, P2Y(1)-mediated changes in cytosolic Ca2+, P2Y(12)-mediated changes in VASP phosphorylation, and metabolism in human plasma. Results: The inhibition of ADP-induced human platelet aggregation and human platelet P2Y12 receptor, and stability in human plasma strongly depended on the stereo-configuration of the chiral P-1 - and P-4-phosphorothioate groups, the SPSP diastereomer being the most potent inhibitor and completely resistant to degradation in plasma, and the RPRP diastereomer being the least potent inhibitor and with the lowest plasma stability. The inhibitory activity of SPRP diastereomers depended on the configuration of the pseudo-asymmetric carbon of the P-2,P-3-chloromethylene group, one of the configurations being significantly more active than the other. Their plasma stability did not differ significantly, being intermediate to that of the SPSP and the RPRP diastereomers. Conclusions: The presently-described stereoisomers have utility for structural, mechanistic, and drug development studies of dual antagonists of platelet P2Y(1) and P2Y(12) receptors. C1 [Chang, Hung; Li, YouFu; Barnard, Marc R.; Michelson, Alan D.; Frelinger, Andrew L., III] Univ Massachusetts, Sch Med, Dept Pediat, Ctr Platelet Funct Studies, Worcester, MA 01605 USA. [Chang, Hung] Chang Gung Univ, Chang Gung Mem Hosp, Div Hematol, Taipei, Taiwan. [Yanachkov, Ivan B.; Dix, Edward J.; Yanachkova, Milka; Wright, George E.] GLSynthesis Inc, Worcester, MA USA. [Michelson, Alan D.; Frelinger, Andrew L., III] Harvard Univ, Sch Med, Dana Farber Canc Inst,Boston Childrens Hosp, Ctr Platelet Res Studies,Div Hematol Oncol, Boston, MA 02115 USA. RP Frelinger, AL (reprint author), Univ Massachusetts, Sch Med, Dept Pediat, Ctr Platelet Funct Studies, Worcester, MA 01605 USA. EM Andrew.Frelinger@childrens.harvard.edu FU SBIR from the National Heart, Lung and Blood Institute [HL081992, HL088828]; CMRP by Chang Gung Memorial Hospital [G380211] FX This work was supported by SBIR grants HL081992 and HL088828 (to I.B. Yanachkov) from the National Heart, Lung and Blood Institute. Support for H. Chang was provided by grant CMRP G380211, provided by Chang Gung Memorial Hospital. There were no other funding sources for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 4 Z9 4 U1 3 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 10 PY 2014 VL 9 IS 4 AR e94780 DI 10.1371/journal.pone.0094780 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5LS UT WOS:000336909100131 PM 24722456 ER PT J AU Wolfe, J Orellana, L Cook, EF Ullrich, C Kang, T Geyer, JR Feudtner, C Weeks, JC Dussel, V AF Wolfe, Joanne Orellana, Liliana Cook, E. Francis Ullrich, Christina Kang, Tammy Geyer, Jeffrey Russell Feudtner, Chris Weeks, Jane C. Dussel, Veronica TI Improving the Care of Children With Advanced Cancer by Using an Electronic Patient-Reported Feedback Intervention: Results From the PediQUEST Randomized Controlled Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; GENERIC CORE SCALES; PHYSICIAN COMMUNICATION; CLINICAL-PRACTICE; OUTCOME MEASURES; ROUTINE PRACTICE; SYMPTOMS; HEALTH; RELIABILITY; VALIDITY AB Purpose This study aimed to determine whether feeding back patient-reported outcomes (PROs) to providers and families of children with advanced cancer improves symptom distress and health-related quality of life (HRQoL). Patients and Methods This study was a parallel, multicentered pilot randomized controlled trial. At most once per week, children age 2 years old with advanced cancer or their parent completed the computer-based Pediatric Quality of Life and Evaluation of Symptoms Technology (PediQUEST) survey consisting of age- and respondent-adapted versions of the Memorial Symptom Assessment Scale (MSAS), Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL4.0), and an overall Sickness question. In the intervention group (n = 51), oncologists and families received printed reports summarizing PROs; e-mails were sent to oncologists and subspecialists when predetermined scores were exceeded. No feedback was provided in the control group (n = 53). Primary outcomes included linear trends of MSAS, PedsQL4.0 total and subscale scores, and Sickness scores during 20 weeks of follow-up, along with child, parent, and provider satisfaction with PediQUEST feedback. Results Feedback did not significantly affect average MSAS, PedsQL4.0, or Sickness score trends. Post hoc subgroup analyses among children age 8 years who survived 20 weeks showed that feedback improved PedsQL4.0 emotional (+8.1; 95% CI, 1.8 to 14.4) and Sickness (-8.2; 95% CI, -14.2 to -2.2) scores. PediQUEST reports were valued by children, parents, and providers and contributed at least sometimes to physician initiation of a psychosocial consult (56%). Conclusion Although routine feedback of PROs did not significantly affect the child's symptoms or HRQoL, changes were in expected directions and improvements observed in emotional HRQoL through exploratory analyses were encouraging. Importantly, children, parents, and providers value PRO feedback. J Clin Oncol 32:1119-1126. (C) 2014 by American Society of Clinical Oncology C1 [Wolfe, Joanne; Ullrich, Christina; Weeks, Jane C.; Dussel, Veronica] Dana Farber Canc Inst, Boston, MA 02215 USA. [Wolfe, Joanne; Ullrich, Christina] Boston Childrens Hosp, Boston, MA USA. [Wolfe, Joanne; Ullrich, Christina; Weeks, Jane C.] Harvard Univ, Sch Med, Boston, MA USA. [Cook, E. Francis] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Orellana, Liliana] Univ Buenos Aires, Buenos Aires, DF, Argentina. [Dussel, Veronica] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Kang, Tammy; Feudtner, Chris] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Kang, Tammy; Feudtner, Chris] Univ Penn, Philadelphia, PA 19104 USA. [Geyer, Jeffrey Russell] Seattle Childrens Hosp, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Geyer, Jeffrey Russell] Univ Washington, Seattle, WA 98195 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA. EM joanne_wolfe@dfci.harvard.edu RI Orellana, Liliana/I-5249-2013; Orellana, Liliana/S-3302-2016 OI Orellana, Liliana/0000-0003-3736-4337; Orellana, Liliana/0000-0003-3736-4337 FU NCI NIH HHS [1K07 CA096746-01, K07 CA096746] NR 52 TC 23 Z9 23 U1 2 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2014 VL 32 IS 11 BP 1119 EP + DI 10.1200/JCO.2013.51.5981 PG 9 WC Oncology SC Oncology GA AG3KG UT WOS:000335314300009 PM 24616307 ER PT J AU Goldkorn, A Ely, B Quinn, DI Tangen, CM Fink, LM Xu, T Twardowski, P Van Veldhuizen, PJ Agarwal, N Carducci, MA Monk, JP Datar, RH Garzotto, M Mack, PC Lara, P Higano, CS Hussain, M Thompson, IM Cote, RJ Vogelzang, NJ AF Goldkorn, Amir Ely, Benjamin Quinn, David I. Tangen, Catherine M. Fink, Louis M. Xu, Tong Twardowski, Przemyslaw Van Veldhuizen, Peter J. Agarwal, Neeraj Carducci, Michael A. Monk, J. Paul, III Datar, Ram H. Garzotto, Mark Mack, Philip C. Lara, Primo, Jr. Higano, Celestia S. Hussain, Maha Thompson, Ian Murchie, Jr. Cote, Richard J. Vogelzang, Nicholas J. TI Circulating Tumor Cell Counts Are Prognostic of Overall Survival in SWOG S0421: A Phase III Trial of Docetaxel With or Without Atrasentan for Metastatic Castration-Resistant Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PREDICTIVE BIOMARKER; PROGRESSION; MEN; CHEMOTHERAPY; ABIRATERONE AB Purpose Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting. J Clin Oncol 32:1136-1142. (C) 2014 by American Society of Clinical Oncology C1 [Goldkorn, Amir; Quinn, David I.; Xu, Tong] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Goldkorn, Amir; Quinn, David I.; Xu, Tong] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Twardowski, Przemyslaw] City Hope Natl Med Ctr, Duarte, CA USA. [Mack, Philip C.; Lara, Primo, Jr.] Univ Calif Davis, Sacramento, CA 95817 USA. [Ely, Benjamin; Tangen, Catherine M.] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Higano, Celestia S.] Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA USA. [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Fink, Louis M.] Nevada Canc Inst, Las Vegas, NV USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Vogelzang, Nicholas J.] US Oncol Res, Las Vegas, NV USA. [Van Veldhuizen, Peter J.] Univ Kansas, Ctr Canc, Westwood, KS USA. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Carducci, Michael A.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Carducci, Michael A.] Eastern Cooperat Oncol Grp, Baltimore, MD USA. [Monk, J. Paul, III] Ohio State Univ, Columbus, OH 43210 USA. [Monk, J. Paul, III] Canc & Leukemia Grp B, Columbus, OH USA. [Datar, Ram H.; Cote, Richard J.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Garzotto, Mark] Portland VA Med Ctr, Portland, OR USA. [Hussain, Maha] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Thompson, Ian Murchie, Jr.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Goldkorn, A (reprint author), USC Keck Sch Med, Dept Internal Med, Div Med Oncol, Los Angeles, CA 90033 USA. EM agoldkor@med.usc.edu RI Quinn, David/F-4343-2015 OI Quinn, David/0000-0002-1411-0417 FU NCI NIH HHS [CA35192, CA014089-38, CA11083, CA12644, CA128567, CA14028, CA16116, CA16385, CA20319, CA21115, CA22433, CA31946, CA31949, CA35090, CA35128, CA35176,, CA35281, CA35421, CA37981, CA42777, CA45377, CA45450, CA45808, CA46282, CA46368, CA58416, CA58723, CA58861, CA58882, CA63845, CA63848, CA68183, CA74647, CA76429, CA76447, CA76448, N01 CA004919, N01 CA013612, N01 CA027057, N01 CA032102, N01 CA035119, N01 CA035176, N01 CA035178, N01 CA035431, N01 CA038926, N01 CA045560, N01 CA045807, N01 CA046441, N01 CA063844, N01 CA067575, P30 CA006973, P30 CA014089, P30 CA093373, R01 CA141077, R01 CA141077-03, U10 CA004919, U10 CA011083, U10 CA013612, U10 CA014028, U10 CA016116, U10 CA020319, U10 CA021115, U10 CA027057, U10 CA031946, U10 CA032102, U10 CA035090, U10 CA035119, U10 CA035128, U10 CA035176, U10 CA035178, U10 CA035192, U10 CA035281, U10 CA035421, U10 CA035431, U10 CA038926, U10 CA042777, U10 CA045377, U10 CA045450, U10 CA045560, U10 CA045807, U10 CA045808, U10 CA046282, U10 CA046368, U10 CA046441, U10 CA058861, U10 CA058882, U10 CA063844, U10 CA063845, U10 CA063848, U10 CA067575, U10 CA074647, U10 CA128567, U10 CA180819, U10 CA180888] NR 32 TC 73 Z9 78 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2014 VL 32 IS 11 BP 1136 EP + DI 10.1200/JCO.2013.51.7417 PG 8 WC Oncology SC Oncology GA AG3KG UT WOS:000335314300011 PM 24616308 ER PT J AU Smith, MR Halabi, S Ryan, CJ Hussain, A Vogelzang, N Stadler, W Hauke, RJ Monk, JP Saylor, P Bhoopalam, N Saad, F Sanford, B Kelly, WK Morris, M Small, EJ AF Smith, Matthew R. Halabi, Susan Ryan, Charles J. Hussain, Arif Vogelzang, Nicholas Stadler, Walter Hauke, Ralph J. Monk, J. Paul Saylor, Philip Bhoopalam, Nirmala Saad, Fred Sanford, Ben Kelly, W. Kevin Morris, Michael Small, Eric J. TI Randomized Controlled Trial of Early Zoledronic Acid in Men With Castration-Sensitive Prostate Cancer and Bone Metastases: Results of CALGB 90202 ( Alliance) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; ORAL SODIUM CLODRONATE; SKELETAL COMPLICATIONS; INCREASED SURVIVAL; LONG-TERM; PREDICTORS AB Purpose Zoledronic acid decreases the risk for skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases but its role earlier in the natural history of the disease is unknown. This phase III study evaluated the efficacy and safety of earlier treatment with zoledronic acid in men with castration-sensitive metastatic prostate cancer. Patients and Methods Men with castration-sensitive prostate cancer and bone metastases whose androgen-deprivation therapy was initiated within 6 months of study entry were randomly assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously every 4 weeks) or a placebo. After their disease progressed to castration-resistant status, all patients received open-label treatment with zoledronic acid. The primary end point was time to first SRE, defined as radiation to bone, clinical fracture, spinal cord compression, surgery to bone, or death as a result of prostate cancer. Target accrual was 680 patients. Primary analysis was planned after 470 SREs. The study was discontinued prematurely (645 patients; 299 SREs) after the corporate supporter withdrew study drug supply. Results Early zoledronic acid was not associated with increased time to first SRE. The median time to first SRE was 31.9 months in the zoledronic acid group (95% CI, 24.2 to 40.3) and 29.8 months in the placebo group (95% CI, 25.3 to 37.2; hazard ratio, 0.97; 95% CI, 0 to 1.17; one-sided stratified log-rank P = .39). Overall survival was similar between the groups (hazard ratio, 0.88; 95% CI, 0.70 to 1.12; P = .29). Rates of adverse events were similar between the groups. Conclusion In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs. J Clin Oncol 32: 1143-1150. (C) 2014 by American Society of Clinical Oncology C1 [Smith, Matthew R.; Saylor, Philip] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. [Halabi, Susan; Sanford, Ben] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Ryan, Charles J.; Small, Eric J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stadler, Walter] Univ Chicago, Chicago, IL 60637 USA. [Bhoopalam, Nirmala] Loyola Univ, Chicago, IL 60611 USA. [Hussain, Arif] Univ Maryland, Baltimore, MD 21201 USA. [Vogelzang, Nicholas] Nevada Canc Res Fdn CCOP, Las Vegas, NV USA. [Hauke, Ralph J.] Univ Nebraska, Omaha, NE 68182 USA. [Monk, J. Paul] Ohio State Univ, Columbus, OH 43210 USA. [Kelly, W. Kevin] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Morris, Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Saad, Fred] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Canc Ctr, Yawkey 7030,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu OI Morris, Michael J./0000-0002-9454-0096 FU NCATS NIH HHS [UL1 TR000430]; NCI NIH HHS [CA45389, CA03927, CA07968, CA16359, CA21060, CA31946, CA31983, CA32291, CA33601, CA35421, CA41287, CA45418, CA47559, CA47577, CA47642, CA59518, CA60138, CA74811, CA77298, CA77406, CA77440, CA77597, CA77651, CA77658, CA86802, K24 CA121990, K24CA121990, P30 CA056036, U10 CA031946, U10 CA033601, U10 CA180867, U10 CA180888] NR 17 TC 55 Z9 55 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 APR 10 PY 2014 VL 32 IS 11 BP 1143 EP + DI 10.1200/JCO.2013.51.6500 PG 9 WC Oncology SC Oncology GA AG3KG UT WOS:000335314300012 PM 24590644 ER PT J AU Ruddy, KJ Gelber, SI Tamimi, RM Ginsburg, ES Schapira, L Come, SE Borges, VF Meyer, ME Partridge, AH AF Ruddy, Kathryn J. Gelber, Shari I. Tamimi, Rulla M. Ginsburg, Elizabeth S. Schapira, Lidia Come, Steven E. Borges, Virginia F. Meyer, Meghan E. Partridge, Ann H. TI Prospective Study of Fertility Concerns and Preservation Strategies in Young Women With Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OVARIAN STIMULATION; AMERICAN-SOCIETY; CHEMOTHERAPY; SURVIVORS; PREMENOPAUSAL; MULTICENTER; LETROZOLE; ESTROGEN; AMENORRHEA; PREGNANCY AB Purpose Most research regarding fertility in young women with breast cancer has focused on long-term survivors. Little is known about how fertility concerns affect treatment decisions or fertility preservation strategies at the time of initial cancer diagnosis. Patients and Methods As part of an ongoing prospective multicenter cohort study, we surveyed women with newly diagnosed early-stage breast cancer at age 40 years. The baseline survey included sociodemographic, medical, and treatment data as well as a modified Fertility Issues Survey, including fertility concern and preservation items. Univariable and multivariable modeling were used to investigate predictors of greater fertility concern. Results Among the first 620 eligible respondents included in this analysis, median age was 37 years (range, 17 to 40 years); 425 women (68%) discussed fertility issues with their physicians before starting therapy, and 319 (51%) were concerned about becoming infertile after treatment. Because of concerns about fertility, four women (1%) chose not to receive chemotherapy, 12 (2%) chose one chemotherapy regimen over another, six (1%) considered not receiving endocrine therapy, 19 (3%) decided not to receive endocrine therapy, and 71 (11%) considered receiving endocrine therapy for < 5 years; 65 (10%) used fertility preservation strategies. Greater concern about fertility was associated with younger age, nonwhite race, not having children, and receipt of chemotherapy. Conclusion Many young women with newly diagnosed breast cancer have concerns about fertility, and for some, these substantially affect their treatment decisions. Only a minority of women currently pursue available fertility preservation strategies in this setting. J Clin Oncol 32:1151-1156. (C) 2014 by American Society of Clinical Oncology C1 [Ruddy, Kathryn J.; Gelber, Shari I.; Meyer, Meghan E.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tamimi, Rulla M.; Ginsburg, Elizabeth S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Come, Steven E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Borges, Virginia F.] Univ Colorado Denver, Aurora, CO USA. RP Ruddy, KJ (reprint author), Mayo Clin, Dept Oncol, 200 First St SW, Rochester, MN 55905 USA. EM ruddy.kathryn@mayo.edu FU NCI NIH HHS [P30 CA046934] NR 26 TC 55 Z9 56 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2014 VL 32 IS 11 BP 1151 EP 1156 DI 10.1200/JCO.2013.52.8877 PG 6 WC Oncology SC Oncology GA AG3KG UT WOS:000335314300013 PM 24567428 ER PT J AU Gandaglia, G Karakiewicz, PI Trinh, QD Sun, M AF Gandaglia, Giorgio Karakiewicz, Pierre I. Quoc-Dien Trinh Sun, Maxine TI Cisplatin-Based Chemotherapy and the Risk of Solid Tumors in Patients With Testicular Nonseminoma: Still a Matter of Debate SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID GERM-CELL TUMORS; ETOPOSIDE; CANCER; SUSCEPTIBILITY; IFOSFAMIDE; BLEOMYCIN C1 [Gandaglia, Giorgio; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Montreal, PQ, Canada. [Gandaglia, Giorgio] Univ Vita Salute San Raffaele, Hosp San Raffaele, Urol Res Inst, Milan, Italy. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, Montreal, PQ, Canada. NR 7 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 APR 10 PY 2014 VL 32 IS 11 BP 1167 EP 1167 DI 10.1200/JCO.2013.53.6482 PG 1 WC Oncology SC Oncology GA AG3KG UT WOS:000335314300016 PM 24590641 ER PT J AU Eikermann, M Velmahos, G Abbara, S Huang, PL Fagan, SP Hirschberg, RE Kwon, JY Nose, V AF Eikermann, Matthias Velmahos, George Abbara, Suhny Huang, Paul L. Fagan, Shawn P. Hirschberg, Ronald E. Kwon, John Y. Nose, Vania TI Case 11-2014: A Man with Traumatic Injuries after a Bomb Explosion at the Boston Marathon SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OPERATION ENDURING FREEDOM; CRITICALLY-ILL PATIENTS; CORONARY-ARTERY; IRAQI FREEDOM; RETRIEVAL; MIGRATION; WOUNDS; PELLET; HEART; VEIN AB A 34-year-old man was brought to the emergency department because of injuries sustained when a bomb exploded at the Boston Marathon. His right leg had been amputated below the knee and his left leg was burned. Imaging showed metallic foreign bodies in the legs, pelvis, and chest. Presentation of CaseDr. John T. Nagurney (Emergency Medicine): A 34-year-old man was brought to the emergency department at this hospital because of multiple traumatic injuries that he sustained when a bomb exploded while he was watching the 2013 Boston Marathon. At the scene, the patient reportedly lost consciousness, had a complete amputation of his right leg directly below the knee, and had copious blood loss. A tourniquet had been applied to the right upper leg. He was placed on a backboard, immobilized, and transported to this hospital by ambulance, arriving at 3:20 p.m., 31 minutes after the explosion. He ... C1 [Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Velmahos, George] Massachusetts Gen Hosp, Dept Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fagan, Shawn P.] Massachusetts Gen Hosp, Dept Burns, Boston, MA 02114 USA. [Hirschberg, Ronald E.] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Kwon, John Y.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Eikermann, Matthias] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Velmahos, George; Fagan, Shawn P.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Kwon, John Y.] Harvard Univ, Sch Med, Dept Orthoped, Boston, MA USA. [Nose, Vania] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. FU Trimed FX Dr. Kwon reports receiving consulting fees from Trimed. No other potential conflict of interest relevant to this article was reported. NR 25 TC 5 Z9 5 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 10 PY 2014 VL 370 IS 15 BP 1441 EP 1451 DI 10.1056/NEJMcpc1314240 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AE6IW UT WOS:000334095200013 PM 24716684 ER PT J AU Hasegawa, K Tsugawa, Y Tsai, CL Brown, DFM Camargo, CA AF Hasegawa, Kohei Tsugawa, Yusuke Tsai, Chu-Lin Brown, David F. M. Camargo, Carlos A., Jr. TI Frequent utilization of the emergency department for acute exacerbation of chronic obstructive pulmonary disease SO RESPIRATORY RESEARCH LA English DT Article DE Chronic obstructive pulmonary disease; Exacerbation; Recurrence; Epidemiology; Emergency service; Hospitalization; Mechanical ventilation; Cost; Healthcare utilization ID UNITED-STATES; COPD; VISITS; HEALTH; HOSPITALIZATIONS; EPIDEMIOLOGY; DECLINE; RATES AB Background: Little is known about patients who frequently visit the emergency department (ED) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We aimed to quantify the proportion and characteristics of patients with frequent ED visits for AECOPD and associated healthcare utilization. Methods: We conducted a retrospective cohort study of adults aged >= 40 years with at least one ED visit for AECOPD between 2010 and 2011, derived from population-based all-payer data of State ED and Inpatient Databases for two large and diverse states: California and Florida. Outcome measures were frequency of ED visits for AECOPD, 30-day ED revisits, subsequent hospitalizations, near-fatal events (AECOPD involving mechanical ventilation), and charges for both ED and inpatient services (available only for Florida) during the year after the first ED visit. Results: The analytic cohort comprised 98,280 unique patients with 154,736 ED visits for AECOPD. During the 1-year period, 29.4% (95% CI, 29.1%-29.7%) of the patients had two or more (frequent) visits, accounting for 55.2% (95% CI, 54.9%-55.4%) of all ED visits for AECOPD. In the multivariable model, significant predictors of frequent ED visits were age 55-74 years (vs. 40-54 years), male sex, non-Hispanic white or black race, Medicaid insurance (vs. private), and lower median household income (all P < 0.001). At the visit-level, 12.3% of ED visits for AECOPD were 30-day revisit events (95% CI, 12.1%-12.4%). Additionally, 62.8% of ED visits for AECOPD (95% CI, 62.6%-63.0%) resulted in a hospitalization; patients with frequent ED visits comprised 55.5% (95% CI, 55.2%-55.8%) of all hospitalizations. Furthermore, 7.3% (95% CI, 7.3%-7.5%) of ED visits for AECOPD led to a near-fatal event; patients with frequent ED visits accounted for 64.4% (95% CI, 63.5%-65.3%) of all near-fatal events. Total charges for AECOPD were $ 1.94 billion (95% CI, $ 1.90-1.97 billion) in Florida; patients with frequent ED visits accounted for $ 1.07 billion (95% CI, $ 1.04-1.09 billion). Conclusions: In this large cohort study, we found that 29% had frequent ED visits for AECOPD and that lower socioeconomic status was significantly associated with a higher frequency of ED visits. Individuals with frequent ED visits for AECOPD accounted for a substantial amount of healthcare utilization and financial burden. C1 [Hasegawa, Kohei; Tsai, Chu-Lin; Brown, David F. M.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hasegawa, Kohei; Tsai, Chu-Lin; Brown, David F. M.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Tsugawa, Yusuke] Harvard Interfaculty Initiat Hlth Policy, Cambridge, MA USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Eleanor and Miles Shore Fellowship Program (Boston, MA); Honjo International Scholarship Foundation (Tokyo, Japan) FX Dr. Hasegawa was supported, in part, by Eleanor and Miles Shore Fellowship Program (Boston, MA). Dr. Tsugawa was supported, in part, by Honjo International Scholarship Foundation (Tokyo, Japan). The funding organizations had 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. NR 34 TC 13 Z9 13 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-993X EI 1465-9921 J9 RESP RES JI Respir. Res. PD APR 10 PY 2014 VL 15 AR 40 DI 10.1186/1465-9921-15-40 PG 13 WC Respiratory System SC Respiratory System GA AG1LN UT WOS:000335176900001 PM 24717062 ER PT J AU Kim, H Dejsuphong, D Adelmant, G Ceccaldi, R Yang, KL Marto, JA D'Andrea, AD AF Kim, Hyungjin Dejsuphong, Donniphat Adelmant, Guillaume Ceccaldi, Raphael Yang, Kailin Marto, Jarrod A. D'Andrea, Alan D. TI Transcriptional Repressor ZBTB1 Promotes Chromatin Remodeling and Translesion DNA Synthesis SO MOLECULAR CELL LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; HOMOLOGOUS RECOMBINATION REPAIR; DOUBLE-STRAND BREAKS; DAMAGE RESPONSE; ZINC-FINGER; HUMAN FIBROBLASTS; UBIQUITIN LIGASE; DVC1 C1ORF124; FACTOR CHD4; REPLICATION AB Timely DNA replication across damaged DNA is critical for maintaining genomic integrity. Translesion DNA synthesis (TLS) allows bypass of DNA lesions using error-prone TLS polymerases. The E3 ligase RAD18 is necessary for proliferating cell nuclear antigen (PCNA) monoubiquitination and TLS polymerase recruitment; however, the regulatory steps upstream of RAD18 activation are less understood. Here, we show that the UBZ4 domain-containing transcriptional repressor ZBTB1 is a critical upstream regulator of TLS. The UBZ4 motif is required for PCNA monoubiquitination and survival after UV damage. ZBTB1 associates with KAP-1, a transcriptional repressor whose phosphorylation relaxes chromatin after DNA damage. ZBTB1 depletion impairs formation of phospho-KAP-1 at UV damage sites and reduces RAD18 recruitment. Furthermore, phosphorylation of KAP-1 is necessary for efficient PCNA modification. We propose that ZBTB1 is required for localizing phospho-KAP-1 to chromatin and enhancing RAD18 accessibility. Collectively, our study implicates a ubiquitin-binding protein in orchestrating chromatin remodeling during DNA repair. C1 [Kim, Hyungjin; Dejsuphong, Donniphat; Ceccaldi, Raphael; Yang, Kailin; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu OI Yang, Kailin/0000-0001-5968-6738 FU Leukemia and Lymphoma Society; NIH [R01DK43889, R37HL52725, 2P01HL048546, P01NS047572] FX We would like to thank Dr. Dipanjan Chowdhury, Dr. Geoffrey Shapiro, Dr. David Kozono (Dana-Farber Cancer Institute), and the members of the D'Andrea laboratory for helpful discussions. We would like to thank Dr. Shunichi Takeda (Kyoto University) for providing DT40 cells. We would also like to thank Joseph Card for sample preparation prior to mass spectrometry analysis. KAP-1 constructs are generous gifts from Dr. Dipanjan Chowdhury (DFCI). H.K. is a recipient of the Leukemia and Lymphoma Society Career Development Fellowship. This work is supported by NIH grants R01DK43889, R37HL52725, and 2P01HL048546 to A.D.D. and P01NS047572 to J.A.M. NR 55 TC 15 Z9 17 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD APR 10 PY 2014 VL 54 IS 1 BP 107 EP 118 DI 10.1016/j.molcel.2014.02.017 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AE9HA UT WOS:000334315900011 PM 24657165 ER PT J AU Sokolowski, E Turina, CB Kikuchi, K Langenau, DM Keller, C AF Sokolowski, E. Turina, C. B. Kikuchi, K. Langenau, D. M. Keller, C. TI Proof-of-concept rare cancers in drug development: the case for rhabdomyosarcoma SO ONCOGENE LA English DT Review DE rhabdomyosarcoma; biomarker; proof-of-concept disease; kinase; rare cancers; drug development ID PRECLINICAL TESTING PROGRAM; CHILDRENS-ONCOLOGY-GROUP; FACTOR-I RECEPTOR; SMALL-MOLECULE INHIBITOR; SOFT-TISSUE SARCOMAS; ENDOTHELIAL GROWTH-FACTOR; PEDIATRIC SOLID TUMORS; T-CELL LYMPHOMA; WILD-TYPE P53; EMBRYONAL RHABDOMYOSARCOMA AB Rare diseases typically affect fewer than 200 000 patients annually, yet because thousands of rare diseases exist, the cumulative impact is millions of patients worldwide. Every form of childhood cancer qualifies as a rare disease-including the childhood muscle cancer, rhabdomyosarcoma (RMS). The next few years promise to be an exceptionally good era of opportunity for public-private collaboration for rare and childhood cancers. Not only do certain governmental regulation advantages exist, but these advantages are being made permanent with special incentives for pediatric orphan drug-product development. Coupled with a growing understanding of sarcoma tumor biology, synergy with pharmaceutical muscle disease drug-development programs, and emerging publically available preclinical and clinical tools, the outlook for academic-community-industry partnerships in RMS drug development looks promising. C1 [Sokolowski, E.; Turina, C. B.] Oregon State Univ, Dept Student Affairs, Corvallis, OR 97331 USA. [Turina, C. B.; Kikuchi, K.; Keller, C.] Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Dept Pediat, Pediat Canc Biol Program, Portland, OR 97239 USA. [Langenau, D. M.] Massachusetts Gen Hosp, Div Mol Pathol, Boston, MA 02114 USA. [Langenau, D. M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Langenau, D. M.] Harvard Univ, Sch Med, Boston, MA USA. [Langenau, D. M.] Harvard Stem Cell Inst, Boston, MA USA. RP Keller, C (reprint author), Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Dept Pediat, Pediat Canc Biol Program, 3181 SW Sam Jackson Pk Rd,MC L321, Portland, OR 97239 USA. EM keller@ohsu.edu OI Kikuchi, Ken/0000-0003-3097-7480 FU Harvard Stem Cell Institute; Ethan Jostad Foundation for Childhood Cancer; [R01CA133229]; [R01CA15923]; [R21CA156056] FX This work was funded by R01CA133229 (CK), R01CA15923 (DML), R21CA156056 (DML), the Harvard Stem Cell Institute and a gift from the Ethan Jostad Foundation for Childhood Cancer. We thank M Imran Aslam, Lara Davis, Ailin Jiang, Leanna Mah, Marissa Peterson, Victoria Reinke, Teagen Settlemeyer, Suman Malempati and R Lor Randall for their contributions to and discussions regarding this topic. Important input on cell lines was made by Karoly Szuhai, Beat Schafer, Frederic Barr, Javed Khan, Corinne Linardic and Peter Houghton. We are grateful for the critical comments of Douglas Hawkins, Malcolm Smith, Idriss Bennani-Baiti, M Simone Nsouli, Parkash Gill, Kathryn Gould, Sandra Smith, Steven Townson, Max Wallace, John Mackintosh, Tommy Pham, Jay Scott, Nadim Nsouli, Christopher Winter and Owen Lockerbie. NR 237 TC 9 Z9 9 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD APR 10 PY 2014 VL 33 IS 15 BP 1877 EP 1889 DI 10.1038/onc.2013.129 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AE9RK UT WOS:000334346300001 PM 23665679 ER PT J AU Choi, YJ Anders, L AF Choi, Y. J. Anders, L. TI Signaling through cyclin D-dependent kinases SO ONCOGENE LA English DT Review DE CDK4; CDK6; cyclin; cell cycle; senescence; apoptosis ID MANTLE CELL LYMPHOMA; T(11-14) CHROMOSOME-TRANSLOCATION; THERAPEUTIC CDK4/6 INHIBITION; TUMOR-SUPPRESSOR GENE; DNA-DAMAGE RESPONSE; E2F TARGET GENES; RETINOBLASTOMA PROTEIN; BREAST-CANCER; TRANSCRIPTION FACTOR; CRYSTAL-STRUCTURE AB Research over the past quarter century has identified cyclin D-dependent kinases, CDK4 and CDK6, as the major oncogenic drivers among members of the CDK superfamily. CDK4/6 are rendered hyperactive in the majority of human cancers through a multitude of genomic alterations. Sustained activation of these protein kinases provides cancer cells with the power to enter the cell cycle continuously by triggering G1-S-phase transitions and dramatically shortening the duration of the G1 phase. It has also become clear, however, that CDK4/6 effectively counter cancer cell-intrinsic tumor suppression mechanisms, senescence and apoptosis, which must be overcome during cell transformation and kept at bay throughout all stages of tumorigenesis. As a central 'node' in cellular signaling networks, cyclin D-dependent kinases sense a plethora of mitogenic signals to orchestrate specific transcriptional programs. As the complexity of the cellular signaling network regulated by these oncogenic kinases unfolds, much remains to be learned about its architecture, its dynamics and the consequences of its perturbation. C1 [Choi, Y. J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Choi, Y. J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Anders, L.] MIT, Whitehead Inst Biomed Res, Dept Biol, Cambridge, MA 02142 USA. RP Anders, L (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge Ctr, Dept Biol, Cambridge, MA 02142 USA. EM lars.anders.hms@gmail.com NR 204 TC 53 Z9 57 U1 4 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD APR 10 PY 2014 VL 33 IS 15 BP 1890 EP 1903 DI 10.1038/onc.2013.137 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AE9RK UT WOS:000334346300002 PM 23644662 ER PT J AU Miller, JA Ding, SL Sunkin, SM Smith, KA Ng, L Szafer, A Ebbert, A Riley, ZL Royall, JJ Aiona, K Arnold, JM Bennet, C Bertagnolli, D Brouner, K Butler, S Caldejon, S Carey, A Cuhaciyan, C Dalley, RA Dee, N Dolbeare, TA Facer, BAC Feng, D Fliss, TP Gee, G Goldy, J Gourley, L Gregor, BW Gu, GY Howard, RE Jochim, JM Kuan, CL Lau, C Lee, CK Lee, F Lemon, TA Lesnar, P McMurray, B Mastan, N Mosqueda, N Naluai-Cecchini, T Ngo, NK Nyhus, J Oldre, A Olson, E Parente, J Parker, PD Parry, SE Stevens, A Pletikos, M Reding, M Roll, K Sandman, D Sarreal, M Shapouri, S Shapovalova, NV Shen, EH Sjoquist, N Slaughterbeck, CR Smith, M Sodt, AJ Williams, D Zollei, L Fischl, B Gerstein, MB Geschwind, DH Glass, IA Hawrylycz, MJ Hevner, RF Huang, H Jones, AR Knowles, JA Levitt, P Phillips, JW Sestan, N Wohnoutka, P Dang, C Bernard, A Hohmann, JG Lein, ES AF Miller, Jeremy A. Ding, Song-Lin Sunkin, Susan M. Smith, Kimberly A. Ng, Lydia Szafer, Aaron Ebbert, Amanda Riley, Zackery L. Royall, Joshua J. Aiona, Kaylynn Arnold, James M. Bennet, Crissa Bertagnolli, Darren Brouner, Krissy Butler, Stephanie Caldejon, Shiella Carey, Anita Cuhaciyan, Christine Dalley, Rachel A. Dee, Nick Dolbeare, Tim A. Facer, Benjamin A. C. Feng, David Fliss, Tim P. Gee, Garrett Goldy, Jeff Gourley, Lindsey Gregor, Benjamin W. Gu, Guangyu Howard, Robert E. Jochim, Jayson M. Kuan, Chihchau L. Lau, Christopher Lee, Chang-Kyu Lee, Felix Lemon, Tracy A. Lesnar, Phil McMurray, Bergen Mastan, Naveed Mosqueda, Nerick Naluai-Cecchini, Theresa Ngo, Nhan-Kiet Nyhus, Julie Oldre, Aaron Olson, Eric Parente, Jody Parker, Patrick D. Parry, Sheana E. Stevens, Allison Pletikos, Mihovil Reding, Melissa Roll, Kate Sandman, David Sarreal, Melaine Shapouri, Sheila Shapovalova, Nadiya V. Shen, Elaine H. Sjoquist, Nathan Slaughterbeck, Clifford R. Smith, Michael Sodt, Andy J. Williams, Derric Zoellei, Lilla Fischl, Bruce Gerstein, Mark B. Geschwind, Daniel H. Glass, Ian A. Hawrylycz, Michael J. Hevner, Robert F. Huang, Hao Jones, Allan R. Knowles, James A. Levitt, Pat Phillips, John W. Sestan, Nenad Wohnoutka, Paul Dang, Chinh Bernard, Amy Hohmann, John G. Lein, Ed S. TI Transcriptional landscape of the prenatal human brain SO NATURE LA English DT Article ID OUTER SUBVENTRICULAR ZONE; RADIAL GLIAL-CELLS; HUMAN FETAL-BRAIN; CEREBRAL-CORTEX; NETWORK ANALYSIS; GENE-EXPRESSION; HUMAN NEOCORTEX; CORTICAL AREAS; MESSENGER-RNA; MOUSE-BRAIN AB The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging(MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. C1 [Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Royall, Joshua J.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A.; Dee, Nick; Dolbeare, Tim A.; Facer, Benjamin A. C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert E.; Jochim, Jayson M.; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A.; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine H.; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael; Sodt, Andy J.; Williams, Derric; Hawrylycz, Michael J.; Jones, Allan R.; Phillips, John W.; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed S.] Allen Inst Brain Sci, Seattle, WA 98103 USA. [Naluai-Cecchini, Theresa; Glass, Ian A.] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. [Stevens, Allison; Zoellei, Lilla; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. [Stevens, Allison; Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Pletikos, Mihovil; Sestan, Nenad] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Pletikos, Mihovil; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA. [Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, Semel Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hevner, Robert F.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98101 USA. [Hevner, Robert F.] Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98105 USA. [Huang, Hao] UT Southwestern Med Ctr, Adv Imaging Res Ctr, Dallas, TX 75390 USA. [Knowles, James A.] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. [Knowles, James A.] Univ So Calif, Dept Psychiat, Los Angeles, CA 90033 USA. [Levitt, Pat] Childrens Hosp, Dept Pediat, Los Angeles, CA 90027 USA. [Levitt, Pat] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. RP Lein, ES (reprint author), Allen Inst Brain Sci, Seattle, WA 98103 USA. EM edl@alleninstitute.org FU National Institutes of Health (NIH) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [5R24HD0008836]; National Institute of Mental Health [RC2MH089921] FX We wish to thank the Allen Institute founders, P. G. Allen and J. Allen, for their vision, encouragement and support. We express our gratitude to past and present Allen Institute staff members R. Adams, A. Alpisa, A. Boe, E. Byrnes, M. Chapin, J. Chen, C. Copeland, N. Dotson, K. Fotheringham, E. Fulfs, M. Gasparrini, T. Gilbert, Z. Haradon, N. Hejazinia, N. Ivanov, J. Kinnunen, A. Kriedberg, J. Laoenkue, S. Levine, V. Menon, E. Mott, N. Motz, J. Pendergraft, L. Potekhina, J. Redmayne-Titley, D. Rosen, C. Simpson, S. Shi, L. Velasquez, U. Wagley, N. Wong and B. Youngstrom for their technical assistance. We would also like to thank J. Augustinack, T. Benner, A. Mayaram, M. Roy, A. van der Kouwe and L. Wald from the Fischl laboratory. Also, we wish to acknowledge Covance Genomics Laboratory (Seattle, Washington) for microarray probe generation, hybridization and scanning. In addition, we express our gratitude to Advanced Bioscience Resources, for providing tissue used for expression profiling and reference atlas generation as well as to the Laboratory of Developmental Biology, University of Washington, for providing tissue used for expression profiling and reference atlas generation. The Laboratory of Developmental Biology work was supported by the National Institutes of Health (NIH) Award Number 5R24HD0008836 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The BrainSpan project was supported by Award Number RC2MH089921 (PIs: E. Lein and M. Hawrylycz, Allen Institute for Brain Science) from the National Institute of Mental Health. The content is solely the responsibility of the respective authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. NR 64 TC 172 Z9 176 U1 9 U2 95 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 10 PY 2014 VL 508 IS 7495 BP 199 EP + DI 10.1038/nature13185 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4UK UT WOS:000333979900036 PM 24695229 ER PT J AU Kraus, D Yang, Q Kong, D Banks, AS Zhang, L Rodgers, JT Pirinen, E Pulinilkunnil, TC Gong, FY Wang, YC Cen, YN Sauve, AA Asara, JM Peroni, OD Monia, BP Bhanot, S Alhonen, L Puigserver, P Kahn, BB AF Kraus, Daniel Yang, Qin Kong, Dong Banks, Alexander S. Zhang, Lin Rodgers, Joseph T. Pirinen, Eija Pulinilkunnil, Thomas C. Gong, Fengying Wang, Ya-chin Cen, Yana Sauve, Anthony A. Asara, John M. Peroni, Odile D. Monia, Brett P. Bhanot, Sanjay Alhonen, Leena Puigserver, Pere Kahn, Barbara B. TI Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity SO NATURE LA English DT Article ID INSULIN-RESISTANCE; ADIPOSE-TISSUE; OXIDATIVE STRESS; CDNA CLONING; EXPRESSION; LIVER; SIRT1; METABOLISM; MOUSE; MICE AB In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes(1). Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity(2). Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue(WAT) from adipose-specific Glut4k-nockout or adipose-specific Glut4-overexpressing mice with their respective controls. NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor(3,4). Nicotinamide is a precursor of NAD(+), an important cofactor linking cellular redox states with energy metabolism(5). SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation(6). Polyamine flux including synthesis, catabolism and excretion, is controlled by the rate-limiting enzymes ornithine decarboxylase (ODC) and spermidine-spermine N-1-acetyltransferase (SSAT; encoded by Sat1) and by polyamine oxidase (PAO), and has a major role in energy metabolism(7,8). We report that NNMT expression is increased in WAT and liver of obese and diabetic mice. Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure. NNMT inhibition increases adipose SAM and NAD(+) levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue. Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism. NNMT inhibition in adipocytes increases oxygen consumption in an ODC-, SSAT- and PAO-dependent manner. Thus, NNMT is a novel regulator of histone methylation, polyamine flux and NAD(+)-dependent SIRT1 signalling, and is a unique and attractive target for treating obesity and type 2 diabetes. C1 [Kraus, Daniel; Yang, Qin; Kong, Dong; Zhang, Lin; Pulinilkunnil, Thomas C.; Gong, Fengying; Wang, Ya-chin; Peroni, Odile D.; Kahn, Barbara B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Kraus, Daniel; Yang, Qin; Kong, Dong; Zhang, Lin; Pulinilkunnil, Thomas C.; Gong, Fengying; Wang, Ya-chin; Asara, John M.; Peroni, Odile D.; Kahn, Barbara B.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Banks, Alexander S.; Rodgers, Joseph T.; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Pirinen, Eija; Alhonen, Leena] Univ Eastern Finland, Bioctr Kuopio, AI Virtanen Inst Mol Sci, FI-70211 Kuopio, Finland. [Cen, Yana; Sauve, Anthony A.] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10065 USA. [Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Monia, Brett P.; Bhanot, Sanjay] ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Kahn, BB (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, 330 Brookline Ave, Boston, MA 02215 USA. EM qin.yang@uci.edu; bkahn@bidmc.harvard.edu RI Cen, Yana/F-4731-2014; Pirinen, Eija/H-9153-2015; Banks, Alexander/B-4832-2012; Pulinilkunnil, Thomas/L-5511-2016 OI Cen, Yana/0000-0001-6436-5744; Pirinen, Eija/0000-0003-1495-3972; Banks, Alexander/0000-0003-1787-6925; Pulinilkunnil, Thomas/0000-0003-1228-893X FU Deutsche Forschungsgemeinschaft [KR 3475/1-1]; American Heart Association (AHA) [09POST2250499]; NIH [R37 DK43051, P30 DK57521, KO8 DK090149, R01 DK100385, BNORC P30 DK046200, NORCH P30 DK040561]; JPB foundation; AHA [13SDG14620005, PF P30 DK0460200]; Ellison Medical Foundation New Scholar in Aging Award; academy of Finland [118590]; [RO1 DK69966]; [P01CA120964]; [P30CA006516-46] FX We thank R. Weinshilboum for NNMT antibody; P. Woster for DFMO; M. Yuan for tandem mass spectrometry; A. Karppinen, A. Korhonen, T. Reponen, A. Uimari, S. Pirnes-Karhu and T. Koponen for measurements of ODC and SSAT activity; C. Semenkovich and S. Fried for protocols for FAS activity measurements; and P. Aryal for assistance with real-time qPCR. D. Kr. is supported by the Deutsche Forschungsgemeinschaft (KR 3475/1-1) and American Heart Association (AHA) (09POST2250499); Q.Y. is a Klarman Scholar at the Beth Israel Deaconess Medical Center. This work is supported by grants from the NIH (R37 DK43051, P30 DK57521) and a grant from the JPB foundation to B. B. K.; grants from the NIH (KO8 DK090149, R01 DK100385, BNORC P30 DK046200 and NORCH P30 DK040561) to Q.Y.; grant RO1 DK69966 to P. P.; P01CA120964 and P30CA006516-46 to J.M.A.; AHA 13SDG14620005 and P&F P30 DK0460200 to D.K.; the Ellison Medical Foundation New Scholar in Aging Award to A. A. S.; and academy of Finland grant 118590 to L.A. NR 43 TC 72 Z9 72 U1 11 U2 88 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 10 PY 2014 VL 508 IS 7495 BP 258 EP + DI 10.1038/nature13198 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4UK UT WOS:000333979900047 PM 24717514 ER PT J AU Spencer, JA Ferraro, F Roussakis, E Klein, A Wu, JW Runnels, JM Zaher, W Mortensen, LJ Alt, C Turcotte, R Yusuf, R Cote, D Vinogradov, SA Scadden, DT Lin, CP AF Spencer, Joel A. Ferraro, Francesca Roussakis, Emmanuel Klein, Alyssa Wu, Juwell Runnels, Judith M. Zaher, Walid Mortensen, Luke J. Alt, Clemens Turcotte, Raphael Yusuf, Rushdia Cote, Daniel Vinogradov, Sergei A. Scadden, David T. Lin, Charles P. TI Direct measurement of local oxygen concentration in the bone marrow of live animals SO NATURE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MODELING PO(2) DISTRIBUTIONS; PROGENITOR CELLS; NICHE; MICROSCOPY; PHOSPHORESCENCE; COMPARTMENT; GRADIENTS; TRACKING; HYPOXIA AB Characterization of how the microenvironment, or niche, regulates stem cell activity is central to understanding stem cell biology and to developing strategies for the therapeutic manipulation of stem cells(1). Low oxygen tension (hypoxia) is commonly thought to be a shared niche characteristic in maintaining quiescence in multiple stem cell types(2-4). However, support for the existence of a hypoxic niche has largely come from indirect evidence such as proteomic analysis(5), expression of hypoxia inducible factor-1 alpha (Hif-1 alpha) and related genes(6), and staining with surrogate hypoxic markers (for example, pimonidazole)(6-8). Here we perform direct in vivo measurements of local oxygen tension (p(O2)) in the bone marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we determined the absolute p(O2) of the bone marrow to be quite low (<32 mm Hg) despite very high vascular density. We further uncovered heterogeneities in local p(O2), with the lowest p(O2) (similar to 9.9 mm Hg, or 1.3%) found in deeper peri-sinusoidal regions. The endosteal region, by contrast, is less hypoxic as it is perfused with small arteries that are often positive for the marker nestin. These p(O2) values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment. C1 [Spencer, Joel A.; Roussakis, Emmanuel; Wu, Juwell; Runnels, Judith M.; Zaher, Walid; Mortensen, Luke J.; Alt, Clemens; Turcotte, Raphael; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Spencer, Joel A.; Wu, Juwell; Runnels, Judith M.; Zaher, Walid; Mortensen, Luke J.; Alt, Clemens; Turcotte, Raphael; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Spencer, Joel A.] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Ferraro, Francesca; Klein, Alyssa; Yusuf, Rushdia; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Ferraro, Francesca; Klein, Alyssa; Yusuf, Rushdia; Scadden, David T.; Lin, Charles P.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Ferraro, Francesca; Klein, Alyssa; Yusuf, Rushdia; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Roussakis, Emmanuel; Vinogradov, Sergei A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Zaher, Walid] King Saud Univ, Coll Med, Dept Anat, Stem Cell Unit, Riyadh 11461, Saudi Arabia. [Turcotte, Raphael] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Cote, Daniel] Univ Laval, Dept Phys Genie Phys & Opt, Quebec City, PQ G1J 2G3, Canada. [Cote, Daniel] Univ Laval, Ctr Rech, Inst Univ Sante Mentale Quebec, Quebec City, PQ G1J 2G3, Canada. RP Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM charles_lin@hms.harvard.edu OI Mortensen, Luke/0000-0002-4331-4099 FU US National Institutes of Health [HL097748, EB017274, HL097794, HL096372, EB014703] FX We thank S. Sakadzic for helpful discussion on setting up the 2PLM experiment. This work was supported by the US National Institutes of Health grant HL097748, EB017274 (to C. P. L.), HL097794, HL096372 and EB014703 (to D.T.S.). NR 32 TC 176 Z9 179 U1 10 U2 103 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 10 PY 2014 VL 508 IS 7495 BP 269 EP + DI 10.1038/nature13034 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4UK UT WOS:000333979900049 PM 24590072 ER PT J AU Khanfar, MA Quinti, L Wang, H Choi, SH Kazantsev, AG Silverman, RB AF Khanfar, Mohammad A. Quinti, Luisa Wang, Hua Choi, Soo Hyuk Kazantsev, Aleksey G. Silverman, Richard B. TI Development and characterization of 3-(benzylsulfonamido) benzamides as potent and selective SIRT2 inhibitors SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE SIRT2; Huntington's disease; 3-(Benzylsulfonamido)benzamides; Polyglutamine aggregation; ADME ID CANCER STEM-CELLS; HUNTINGTONS-DISEASE; POLYGLUTAMINE AGGREGATION; DOWN-REGULATION; SIRTUINS; DISCOVERY; DESIGN; IDENTIFICATION; DEACETYLASES; DERIVATIVES AB Inhibitors of sirtuin-2 deacetylase (SIRT2) have been shown to be protective in various models of Huntington's disease (HD) by decreasing polyglutamine aggregation, a hallmark of HD pathology. The present study was directed at optimizing the potency of SIRT2 inhibitors containing the neuroprotective sulfobenzoic acid scaffold and improving their pharmacology. To achieve that goal, 176 analogues were designed, synthesized, and tested in deacetylation assays against the activities of major human sirtuins SIRT1-3. This screen yielded 15 compounds with enhanced potency for SIRT2 inhibition and 11 compounds having SIRT2 inhibition equal to reference compound AK-1. The newly synthesized compounds also demonstrated higher SIRT2 selectivity over SIRT1 and SIRT3. These candidates were subjected to a dose-response bioactivity assay, measuring an increase in alpha-tubulin K40 acetylation in two neuronal cell lines, which yielded five compounds bioactive in both cell lines and eight compounds bioactive in at least one of the cell lines tested. These bioactive compounds were subsequently tested in a tertiary polyglutamine aggregation assay, which identified five inhibitors. ADME properties of the bioactive SIRT2 inhibitors were assessed, which revealed a significant improvement of the pharmacological properties of the new entities, reaching closer to the goal of a clinically-viable candidate. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Khanfar, Mohammad A.; Wang, Hua; Choi, Soo Hyuk; Silverman, Richard B.] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Chem,Dept Mol Biosci, Evanston, IL 60208 USA. [Khanfar, Mohammad A.] Univ Jordan, Dept Pharmaceut Sci, Amman, Jordan. [Quinti, Luisa; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Quinti, Luisa; Kazantsev, Aleksey G.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Silverman, RB (reprint author), Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Chem,Dept Mol Biosci, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM akazantsev@mgh.harvard.edu; Agman@chem.northwestern.edu FU National Institutes of Health [U01 NS066912] FX The authors are grateful to the National Institutes of Health (Grant U01 NS066912) for financial support of this research. NR 42 TC 10 Z9 10 U1 0 U2 12 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 EI 1768-3254 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD APR 9 PY 2014 VL 76 BP 414 EP 426 DI 10.1016/j.ejmech.2014.02.003 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AG5VS UT WOS:000335487400038 PM 24602787 ER PT J AU Franchetti, Y Ide, H AF Franchetti, Yoko Ide, Hiroo TI Socio-demographic and lifestyle factors for child's physical growth and adiposity rebound of Japanese children: a longitudinal study of the 21st century longitudinal survey in newborns SO BMC PUBLIC HEALTH LA English DT Article DE Obesity; Adiposity rebound (AR); Body mass index (BMI); Longitudinal survey; Lifestyle ID BODY-MASS INDEX; BIRTH COHORT; OBESITY; AGE; OVERWEIGHT; ADULTHOOD; BMI; ADOLESCENTS; SCHOOL; RISK AB Background: It is unknown whether childhood physical development in Asian populations differs from western populations, since no longitudinal analysis has been performed in Asian countries yet. Utilizing the 21st Century Longitudinal Survey in Newborns, we studied the timing of adiposity rebound (AR) among Japanese children and determined whether AR occurs earlier in obese children compared to nonobese children. Furthermore, we identified important demographic, social, and lifestyle factors that affect their physical development. Methods: We used data from the annual surveillance of Japanese children born in 2001, with 45,392 eligible subjects. We applied survival analysis to evaluate the AR and a trajectory method for the BMI transition across 5 1/2 years. Time-dependent and time-independent factors affecting BMI changes were investigated using longitudinal analysis. Accounting for the known difference in prevalence between Japanese and Western children, we adopted a 95th percentile of BMI as criterion for obesity. Results: Mean BMI at birth and at ages 1 1/2, 2 1/2, 3 1/2, 4 1/2, and 5 1/2 years for all subjects were 12.6, 16.3, 16.1, 15.8, 15.5, and 15.4, respectively, showing a progressive reduction after 1 1/2 years. However, among obese children at 5 1/2 years, 39.6% had experienced AR as early as at age 4 1/2 years. Controlling for sex, Cox's proportional hazards model showed that obese children had a 48.5% higher hazard to experience AR than nonobese children. The difference in BMI transition between obese and non-obese children was also captured by a trajectory method. In longitudinal analysis, BMI was lower for children who had a longer gestational period whereas children who received parental care from non-family members gained higher BMI values. Conclusions: With the 95th percentile cutoff for children obesity, obese Japanese children developed AR earlier than nonobese Japanese children, similar to those in Western countries reported in the literature. Primary caretakers and length of gestational period were the most important socio-demographic factors affecting physical development. C1 [Franchetti, Yoko] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Franchetti, Yoko] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ide, Hiroo] Chiba Univ Hosp, Div Res, Hlth Policy Aging Soc, Chuo Ku, Chiba, Japan. RP Ide, H (reprint author), Chiba Univ Hosp, Div Res, Hlth Policy Aging Soc, Chuo Ku, Inohana 1-8-1, Chiba, Japan. EM ide@chiba-u.jp FU Health and Labour Sciences Research Grant, Ministry of Health, Labour and Welfare, Japan FX This study was supported by Health and Labour Sciences Research Grant, Ministry of Health, Labour and Welfare, Japan. NR 40 TC 3 Z9 3 U1 0 U2 2 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 APR 9 PY 2014 VL 14 AR 334 DI 10.1186/1471-2458-14-334 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG6AF UT WOS:000335500000001 PM 24716901 ER PT J AU Pugh, MJ Leykum, LK Lanham, HJ Finley, EP Noel, PH McMillan, KK Pugh, JA AF Pugh, Mary Jo Leykum, Luci K. Lanham, Holly J. Finley, Erin P. Noel, Polly H. McMillan, Katharine K. Pugh, Jacqueline A. TI Implementation of the epilepsy center of excellence to improve access to and quality of care - protocol for a mixed methods study SO IMPLEMENTATION SCIENCE LA English DT Article DE Epilepsy; Relational Coordination; Veterans Health Administration (VA) ID HEALTH-CARE; RELATIONAL COORDINATION; ANTIEPILEPTIC DRUG; SURGICAL-PATIENTS; IMPACT; OUTCOMES; ORGANIZATIONS; MECHANISMS; VETERANS; SERVICES AB Background: To address the growing problem of epilepsy among aging Veterans and younger Veterans who have experienced a traumatic brain injury (TBI), the Veterans Health Administration (VA) has implemented 16 Epilepsy Centers of Excellence (ECOE) to assure increased access to high quality of care for Veterans with epilepsy. Each ECOE consists of a network of regional hubs to which spoke facilities refer Veterans for subspecialty treatment. The ECOEs are expected to improve access to and quality of epilepsy care through patient care, consultation and education. This study aims to: evaluate the effectiveness of the ECOE structure by describing changes in the quality of and access to care for epilepsy before and after the ECOE initiative using QUality Indicators in Epilepsy Treatment (QUIET Indicators); describe associations between changes in the structure and processes of care and Relational Coordination (RC), a model of task-oriented communication that has been shown to play a role in implementation science; and determine if variations in care are related to levels of RC. Methods: This four-year comparative case study uses a mixed-methods approach. We will use VA inpatient, outpatient, pharmacy, and chart abstraction data to identify changes in the quality of and access to epilepsy care in the VA between Fiscal Year 2008 and Fiscal Year 2014. Qualitative and survey methods will be used to identify changes in the structure and processes of epilepsy care and RC over the course of the study. We will then link data from the first two objectives to determine the extent to which quality of and access to epilepsy care is associated with RC using multivariable models. Discussion: This innovative study has the potential to improve understanding of hub-and-spoke model effectiveness, VA epilepsy care, and models of epilepsy specialty care more globally. Moreover, it contributes to implementation science by advancing understanding of the role of RC in the context of a major transformation in the structure of care delivery in a national integrated healthcare system. C1 [Pugh, Mary Jo; Leykum, Luci K.; Lanham, Holly J.; Finley, Erin P.; Noel, Polly H.; McMillan, Katharine K.; Pugh, Jacqueline A.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Pugh, Mary Jo] VA Epilepsy Ctr Excellence, San Antonio, TX 78229 USA. RP Pugh, MJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, 7400 Merton Minter BLVD, San Antonio, TX 78229 USA. EM Maryjo.Pugh2@va.gov OI Pugh, Jacqueline/0000-0003-4933-141X; Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 FU Department of Veterans Affairs, VA Health Services Research and Development Service [IIR-062]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI) FX This project was funded by the Department of Veterans Affairs, VA Health Services Research and Development Service (IIR-062; MJ Pugh PI). Dr. Finley is an investigator with the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University in St. Louis; through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI). NR 38 TC 4 Z9 4 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD APR 9 PY 2014 VL 9 AR 44 DI 10.1186/1748-5908-9-44 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AF7KI UT WOS:000334893300001 PM 24712733 ER PT J AU Horiya, S Bailey, JK Temme, JS Schippe, YVG Krauss, IJ AF Horiya, Satoru Bailey, Jennifer K. Temme, J. Sebastian Schippe, Yollete V. Guillen Krauss, Isaac J. TI Directed Evolution of Multivalent Glycopeptides Tightly Recognized by HIV Antibody 2G12 SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO SELECTION; MESSENGER-RNA DISPLAY; VACCINE DESIGN; DC-SIGN; OLIGOMANNOSE CLUSTERS; CARBOHYDRATE EPITOPE; PURIFIED COMPONENTS; RIBOSOMAL SYNTHESIS; UNNATURAL PEPTIDES AB Herein, we report a method for in vitro selection of multivalent glycopeptides, combining mRNA display with incorporation of unnatural amino acids and "click" chemistry. We have demonstrated the use of this method to design potential glycopeptide vaccines against HIV. From libraries of similar to 10(13) glycopeptides containing multiple Man(9) glycan(s), we selected variants that bind to HIV broadly neutralizing antibody 2G12 with picomolar to low nanomolar affinity. This is comparable to the strength of the natural 2G12-gp120 interaction, and is the strongest affinity achieved to date with constructs containing 3-5 glycans. These glycopeptides are therefore of great interest in HIV vaccine design. C1 [Horiya, Satoru; Bailey, Jennifer K.; Temme, J. Sebastian; Krauss, Isaac J.] Brandeis Univ, Dept Chem, Waltham, MA 02454 USA. [Schippe, Yollete V. Guillen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Schippe, Yollete V. Guillen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Schippe, YVG (reprint author), 3B Pharmaceut GmbH, Magnusstr 11, D-12489 Berlin, Germany. EM yolleteg@gmail.com; kraussi@brandeis.edu FU Brandeis University; NIH [R01 AI090745] FX I.J.K. gratefully acknowledges Brandeis University and the NIH (R01 AI090745). We are grateful to Polymun Scientific for a gift of mAb 2G12, to Prof. Bradley Pentelute for assistance with rapid flow solid-phase peptide synthesis, and to Prof. Jack Szostak for providing S.H. with the opportunity to learn mRNA display techniques in his laboratory. NR 59 TC 27 Z9 27 U1 6 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 9 PY 2014 VL 136 IS 14 BP 5407 EP 5415 DI 10.1021/ja500678v PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA AF2WC UT WOS:000334572200042 PM 24645849 ER PT J AU Costa, SCP Lesser, CF AF Costa, Sonia C. P. Lesser, Cammie F. TI A Multifunctional Region of the Shigella Type 3 Effector IpgB1 Is Important for Secretion from Bacteria and Membrane Targeting in Eukaryotic Cells SO PLOS ONE LA English DT Article ID III SECRETION; SACCHAROMYCES-CEREVISIAE; VIRULENCE PROTEINS; PSEUDOMONAS-EXOS; MAMMALIAN-CELLS; INVASION; SYSTEM; MACHINERY; YEAST; MOTIF AB Type 3 secretion systems are complex nanomachines used by many Gram-negative bacteria to deliver tens of proteins (effectors) directly into host cells. Once delivered into host cells, effectors often target to specific cellular loci where they usurp host cell processes to their advantage. Here, using the yeast model system, we identify the membrane localization domain (MLD) of IpgB1, a stretch of 20 amino acids enriched for hydrophobic residues essential for the targeting of this effector to the plasma membrane. Embedded within these residues are ten that define the IpgB1 chaperone-binding domain for Spa15. As observed with dedicated class IA chaperones that mask hydrophobic MLDs, Spa15, a class IB chaperone, promotes IpgB1 stability by binding this hydrophobic region. However, despite being stable, an IpgB1 allele that lacks the MLD is not recognized as a secreted substrate. Similarly, deletion of the chaperone binding domains of IpgB1 and three additional Spa15-dependent effectors result in alleles that are no longer recognized as secreted substrates despite the presence of intact N-terminal secretion signal sequences. This is in contrast with MLD-containing effectors that bind class IA dedicated chaperones, as deletion of the MLD of these effectors alleviates the chaperone requirement for secretion. These observations indicate that at least for substrates of class IB chaperones, the chaperone-effector complex plays a major role in defining type 3 secreted proteins and highlight how a single region of an effector can play important roles both within prokaryotic and eukaryotic cells. C1 [Lesser, Cammie F.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med Microbiol & Immunol, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lesser, CF (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med Microbiol & Immunol, Cambridge, MA USA. EM clesser@mgh.harvard.edu FU National Institutes of Health [R01 AI064285, R21 AI096134] FX Work was conducted through support from the National Institutes of Health (R01 AI064285 and R21 AI096134). 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 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2014 VL 9 IS 4 AR e93461 DI 10.1371/journal.pone.0093461 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE9PC UT WOS:000334339000034 PM 24718571 ER PT J AU Kelley, JM Kraft-Todd, G Schapira, L Kossowsky, J Riess, H AF Kelley, John M. Kraft-Todd, Gordon Schapira, Lidia Kossowsky, Joe Riess, Helen TI The Influence of the Patient-Clinician Relationship on Healthcare Outcomes: A Systematic Review and MetaAnalysis of Randomized Controlled Trials SO PLOS ONE LA English DT Review ID INCREASE PHYSICAL-ACTIVITY; PRACTITIONER AGREEMENT; PUBLICATION BIAS; COMMUNICATION; INTERVENTION AB Objective: To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes. Design: Systematic review and meta-analysis. Data Sources: Electronic databases EMBASE and MEDLINE and the reference sections of previous reviews. Eligibility Criteria for Selecting Studies: Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions. Results: Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = 2.23 to.66. Using a random-effects model, the estimate of the overall effect size was small (d =.11), but statistically significant (p =.02). Conclusions: This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic. C1 [Kelley, John M.; Kraft-Todd, Gordon; Schapira, Lidia; Riess, Helen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Empathy & Relat Sci Program, Boston, MA 02115 USA. [Kossowsky, Joe] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Placebo Studies & Therapeut Encounter, Boston, MA USA. [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA USA. [Schapira, Lidia] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kossowsky, Joe] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Kossowsky, Joe] Univ Basel, Dept Clin Psychol & Psychotherapy, Basel, Switzerland. RP Kelley, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Empathy & Relat Sci Program, Boston, MA 02115 USA. EM johnkelley@post.harvard.edu FU Arnold P. Gold Foundation [FI-11-004]; Swiss National Science Foundation [P2BSP1_148628] FX This study was made possible with a grant from the Arnold P. Gold Foundation (www.humanism-in-medicine.org; grant # FI-11-004). Joe Kossowsky's contributions to this study were supported by the Swiss National Science Foundation, grant project (P2BSP1_148628). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 46 Z9 46 U1 2 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2014 VL 9 IS 4 DI 10.1371/journal.pone.0094207 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE9PC UT WOS:000334339000090 ER PT J AU Dasgupta, S Erturk-Hasdemir, D Ochoa-Reparaz, J Reinecker, HC Kasper, DL AF Dasgupta, Suryasarathi Erturk-Hasdemir, Deniz Ochoa-Reparaz, Javier Reinecker, Hans-Christian Kasper, Dennis L. TI Plasmacytoid Dendritic Cells Mediate Anti-inflammatory Responses to a Gut Commensal Molecule via Both Innate and Adaptive Mechanisms SO CELL HOST & MICROBE LA English DT Article ID REGULATORY T-CELLS; INDUCIBLE COSTIMULATOR LIGAND; ORAL TOLERANCE; ZWITTERIONIC POLYSACCHARIDES; INDOLEAMINE 2,3-DIOXYGENASE; INTESTINAL INFLAMMATION; IMMUNE-RESPONSES; HUMAN MICROBIOTA; SIGLEC-H; INDUCTION AB Polysaccharide A (PSA), the archetypical immunomodulatory molecule of the gut commensal Bacteroides fragilis, induces regulatory T cells to secrete the anti-inflammatory cytokine interleukin-10 (IL-10). The cellular mediators of PSA's immunomodulatory properties are incompletely understood. In a mouse model of colitis, we find that PSA requires both innate and adaptive immune mechanisms to generate protection. Plasmacytoid DCs (PDCs) exposed to PSA do not produce proinflammatory cytokines, but instead they specifically stimulate IL-10 secretion by CD4+ T cells and efficiently mediate PSA-afforded immunoprotection. PSA induces and preferentially ligates Toll-like receptor 2 on PDCs but not on conventional DCs. Compared with other TLR2 ligands, PSA is better at enhancing PDC expression of costimulatory molecules required for protection against colitis. PDCs can thus orchestrate the beneficial immunoregulatory interaction of commensal microbial molecules, such as PSA, through both innate and adaptive immune mechanisms. C1 [Dasgupta, Suryasarathi; Erturk-Hasdemir, Deniz; Kasper, Dennis L.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Ochoa-Reparaz, Javier] Univ Calif Santa Barbara, Ctr Nanomed, Sanford Burnham Med Res Inst, Santa Barbara, CA 93106 USA. [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Kasper, DL (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. EM dennis_kasper@hms.harvard.edu FU Crohn's and Colitis Foundation of America; R21 NIAID [AI1090102] FX This work was supported by a Senior Research Award from the Crohn's and Colitis Foundation of America and R21 NIAID (AI1090102) to D. L. K. We thank B. Reinap, R. T. Bronson, and J. McCoy for PSA purification, histopathology discussions, and editorial expertise, respectively; N. Reading, H. Chun, E. Troy, and N. Surana for technical help; and Diane Mathis (Harvard Medical School) for manuscript review and helpful suggestions. NR 49 TC 43 Z9 44 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD APR 9 PY 2014 VL 15 IS 4 BP 413 EP 423 DI 10.1016/j.chom.2014.03.006 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AE8VL UT WOS:000334280900006 PM 24721570 ER PT J AU Huijbers, W Mormino, EC Wigman, SE Ward, AM Vannini, P McLaren, DG Becker, JA Schultz, AP Hedden, T Johnson, KA Sperling, RA AF Huijbers, Willem Mormino, Elizabeth C. Wigman, Sarah E. Ward, Andrew M. Vannini, Patrizia McLaren, Donald G. Becker, J. Alex Schultz, Aaron P. Hedden, Trey Johnson, Keith A. Sperling, Reisa A. TI Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloid; default network; entorhinal cortex; fMRI; memory; preclinical Alzheimer's disease ID INTRINSIC FUNCTIONAL CONNECTIVITY; EARLY ALZHEIMERS-DISEASE; BRAINS DEFAULT NETWORK; ENCODING/RETRIEVAL FLIP; MEMORY PERFORMANCE; BETA DEPOSITION; LIFE-SPAN; POSTEROMEDIAL CORTEX; CLINICAL DECLINE; VERBAL MEMORY AB Normal aging is often difficult to distinguish from the earliest stages of Alzheimer's disease. Years before clinical memory deficits manifest, amyloid-beta deposits in the cortex in many older individuals. Neuroimaging studies indicate that a set of densely connected neocortical regions, referred to as the default network, is especially vulnerable to amyloid-beta deposition. Yet, the impact of amyloid-beta on age-related changes within the medial temporal lobe (MTL) memory system is less clear. Here we demonstrate that cognitively normal older humans, compared with young adults, show reduced ability to modulate hippocampal activations and entorhinal deactivations during an episodic memory task. Among older adults, amyloid-beta deposition was associated with failure to modulate activity in entorhinal cortex, but not hippocampus. Furthermore, we show that entorhinal regions demonstrating amyloid-beta-related dysfunction are directly connected to the neocortical regions of the default network. Together these findings link neocortical amyloid-beta deposition to neuronal dysfunction specifically in entorhinal cortex, while aging is associated with more widespread functional changes across the MTL. C1 [Huijbers, Willem; Wigman, Sarah E.; Ward, Andrew M.; Vannini, Patrizia; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Huijbers, Willem; Mormino, Elizabeth C.; Wigman, Sarah E.; Ward, Andrew M.; Vannini, Patrizia; McLaren, Donald G.; Becker, J. Alex; Schultz, Aaron P.; Hedden, Trey; Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Huijbers, Willem; Mormino, Elizabeth C.; Wigman, Sarah E.; Ward, Andrew M.; Vannini, Patrizia; McLaren, Donald G.; Becker, J. Alex; Schultz, Aaron P.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Aging Brain Study, Dept Neurol, Boston, MA 02114 USA. [Hedden, Trey; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Huijbers, W (reprint author), Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL 104, Boston, MA 02115 USA. EM huijbers@nmr.mgh.harvard.edu FU European Molecular Biology Organization [ALTF 318-2011]; Marie Curie Fellowship FP7 [PEOPLE-2007-4-1-IOF]; National Institutes of Health [F32 AG044054, F32 AG042228, K01 AG040197, K24 AG035007, P01AG036694, P50AG005134]; Alzheimer's Association Grant [IIRG-06- AG027435]; Center for Functional Neuroimaging Technologies [P41EB015896]; P41 Biotechnology Resource Grant [National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health.] FX This research was supported by European Molecular Biology Organization Grant ALTF 318-2011 (W.H.); Marie Curie Fellowship FP7-PEOPLE-2007-4-1-IOF (P.V.); National Institutes of Health Grants F32 AG044054 (E.C.M.), F32 AG042228 (D.M.), K01 AG040197 (T.H.), K24 AG035007 (R.S.), (R.S.), P01AG036694 (R.S./ K.A.J.), and P50AG005134 (R.S.); and the Alzheimer's Association Grant IIRG- 06-27374 (K.A.J.).This research was performed in whole or in part at the Athinoula A.Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies Grant P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. NR 92 TC 18 Z9 18 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 9 PY 2014 VL 34 IS 15 BP 5200 EP 5210 DI 10.1523/JNEUROSCI.3579-13.014 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AE9RX UT WOS:000334347700014 PM 24719099 ER PT J AU Hecker, L Logsdon, NJ Kurundkar, D Kurundkar, A Bernard, K Hock, T Meldrum, E Sanders, YY Thannickal, VJ AF Hecker, Louise Logsdon, Naomi J. Kurundkar, Deepali Kurundkar, Ashish Bernard, Karen Hock, Thomas Meldrum, Eric Sanders, Yan Y. Thannickal, Victor J. TI Reversal of Persistent Fibrosis in Aging by Targeting Nox4-Nrf2 Redox Imbalance SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; GROWTH-FACTOR-BETA; HUMAN FIBROBLASTS; KIDNEY-DISEASE; LUNG FIBROSIS; MYOFIBROBLAST; SENESCENCE; TISSUE; DIFFERENTIATION; BLEOMYCIN AB The incidence and prevalence of pathological fibrosis increase with advancing age, although mechanisms for this association are unclear. We assessed the capacity for repair of lung injury in young ( 2 months) and aged ( 18 months) mice. Whereas the severity of fibrosis was not different between these groups, aged mice demonstrated an impaired capacity for fibrosis resolution. Persistent fibrosis in lungs of aged mice was characterized by the accumulation of senescent and apoptosis-resistant myofibroblasts. These cellular phenotypes were sustained by alterations in cellular redox homeostasis resulting from elevated expression of the reactive oxygen species-generating enzyme Nox4 [ NADPH ( reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-4] and an impaired capacity to induce the Nrf2 ( NFE2-related factor 2) antioxidant response. Lung tissues from human subjects with idiopathic pulmonary fibrosis ( IPF), a progressive and fatal lung disease, also demonstrated this Nox4-Nrf2 imbalance. Nox4 mediated senescence and apoptosis resistance in IPF fibroblasts. Genetic and pharmacological targeting of Nox4 in aged mice with established fibrosis attenuated the senescent, antiapoptotic myofibroblast phenotype and led to a reversal of persistent fibrosis. These studies suggest that loss of cellular redox homeostasis promotes profibrotic myofibroblast phenotypes that result in persistent fibrosis associated with aging. Our studies suggest that restoration of Nox4-Nrf2 redox balance in myofibroblasts may be a therapeutic strategy in age-associated fibrotic disorders, potentially able to resolve persistent fibrosis or even reverse its progression. C1 [Hecker, Louise; Logsdon, Naomi J.; Kurundkar, Deepali; Kurundkar, Ashish; Bernard, Karen; Hock, Thomas; Sanders, Yan Y.; Thannickal, Victor J.] Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Hecker, Louise] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Meldrum, Eric] Genkyotex, CH-1228 Geneva, Switzerland. RP Hecker, L (reprint author), Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. EM lhecker@uab.edu; vjthan@uab.edu FU Veterans Administration Health System [1IK2BX001477]; NIH [P01 HL 114470, R01 HL094230, P50 HL107181] FX Supported by Veterans Administration Health System grant 1IK2BX001477 (L.H.) and NIH grants P01 HL 114470, R01 HL094230, and P50 HL107181 (V.J.T.) NR 45 TC 64 Z9 65 U1 2 U2 20 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 9 PY 2014 VL 6 IS 231 AR 231ra47 DI 10.1126/scitranslmed.3008182 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AE9QR UT WOS:000334343900003 PM 24718857 ER PT J AU Greene, SJ Alkhawam, L Vaduganathan, M AF Greene, Stephen J. Alkhawam, Lora Vaduganathan, Muthiah TI Dual Antiplatelet Therapy After Stent Implantation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ELUTING STENTS; TRIAL C1 [Greene, Stephen J.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60601 USA. [Alkhawam, Lora] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60601 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Greene, SJ (reprint author), Northwestern Univ, Feinberg Sch Med, 201 E Huron St, Chicago, IL 60601 USA. EM stephen-greene@md.northwestern.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 9 PY 2014 VL 311 IS 14 BP 1446 EP 1446 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AE4EP UT WOS:000333935000026 PM 24715081 ER PT J AU Jordan, JT Sellner, J Struhal, W Schneider, L Mayans, D AF Jordan, Justin T. Sellner, Johann Struhal, Walter Schneider, Logan Mayans, David TI International Issues: Obtaining an adult neurology residency position in the United States An overview SO NEUROLOGY LA English DT Editorial Material AB Around the world, there are marked differences in neurology training, including training duration and degree of specialization. In the United States, adult neurology residency is composed of 1 year of internal medicine training (preliminary year) and 3 years of neurology-specific training. Child neurology, which is not the focus of this article, is 2 years of pediatrics and 3 years of neurology training. The route to adult neurology residency training in the United States is standardized, and is similar to most other US specialties. Whereas US medical graduates often receive stepwise guidance from their medical school regarding application for residency training, international graduates often enter this complex process with little or no such assistance. Despite this discrepancy, about 10%-15% of residency positions in the United States are filled by international medical graduates.(1,2) In adult neurology specifically, 35% of matched positions were filled by international graduates in 2013, 75% of which were not US citizens.(1) In an effort to provide a preliminary understanding of the application process and related terminology (table 1), and thereby encourage international residency applicants, we describe the steps necessary to apply for neurology residency in the United States. C1 [Jordan, Justin T.] Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02114 USA. [Sellner, Johann] Paracelsus Med Univ, Christian Doppler Klin, Dept Neurol, Salzburg, Austria. [Sellner, Johann] Tech Univ Munich, Dept Neurol, Klinikum Rechts Isar, D-80290 Munich, Germany. [Struhal, Walter] Gen Hosp City Linz, Dept Neurol, Linz, Austria. [Schneider, Logan] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Mayans, David] Neurol Consultants Kansas, Wichita, KS USA. RP Jordan, JT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02114 USA. EM jtjordan@partners.org NR 2 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR 8 PY 2014 VL 82 IS 14 BP E112 EP E115 DI 10.1212/WNL.0000000000000279 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AH9WY UT WOS:000336497000001 PM 24711537 ER PT J AU Inlay, MA Serwold, T Mosley, A Fathman, JW Dimov, IK Seita, J Weissman, IL AF Inlay, Matthew A. Serwold, Thomas Mosley, Adriane Fathman, John W. Dimov, Ivan K. Seita, Jun Weissman, Irving L. TI Identification of Multipotent Progenitors that Emerge Prior to Hematopoietic Stem Cells in Embryonic Development SO STEM CELL REPORTS LA English DT Article ID MURINE YOLK-SAC; MOUSE EMBRYO; AGM REGION; IN-VIVO; PARAAORTIC SPLANCHNOPLEURA; DEFINITIVE HSCS; FETAL LIVER; CIRCULATION; PLACENTA; RECEPTOR AB Hematopoiesis in the embryo proceeds in a series of waves, with primitive erythroid-biased waves succeeded by definitive waves, within which the properties of hematopoietic stem cells (multilineage potential, self-renewal, and engraftability) gradually arise. Whereas self-renewal and engraftability have previously been examined in the embryo, multipotency has not been thoroughly addressed, especially at the single-cell level or within well-defined populations. To identify when and where clonal multilineage potential arises during embryogenesis, we developed a single-cell multipotency assay. We find that, during the initiation of definitive hematopoiesis in the embryo, a defined population of multipotent, engraftable progenitors emerges that is much more abundant within the yolk sac (YS) than the aortagonad- mesonephros (AGM) or fetal liver. These experiments indicate that multipotent cells appear in concert within both the YS and AGM and strongly implicate YS-derived progenitors as contributors to definitive hematopoiesis. C1 [Inlay, Matthew A.; Mosley, Adriane; Fathman, John W.; Dimov, Ivan K.; Seita, Jun; Weissman, Irving L.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Serwold, Thomas] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Fathman, John W.] Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. [Weissman, Irving L.] Stanford Univ, Sch Med, Ludwig Ctr Canc Stem Cell Res & Med, Stanford, CA 94305 USA. RP Inlay, MA (reprint author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. EM minlay@uci.edu OI Seita, Jun/0000-0002-3008-3615 FU National Institutes of Health [5 T32 AI07290, R01HL058770, R01CA86085, U01HL09999]; California Institute for Stem Cell Research [T1-00001, RT2-02060]; Harvard Stem Cell Institute; Siebel Stem Cell Institute; Thomas and Stacey Siebel Foundation; Virginia and D.K. Ludwig Fund for Cancer Research FX The authors wish to thank Adriel Cha, Charles Chan, Nate Fernhoff, Katharina Seiler, Shah Ali, Bevin Brady, Debashis Sahoo, Kyle Loh, Seth Karten, Pamela Wenzel, and Roger Pedersen for sharing reagents and expertise; Libuse Jerabek and Terry Storm for lab management; Teja Naik and Chrissy Muscat for antibody conjugation; and Charlene Wang, Aaron McCarty, Humberto Contreas-Trujillo, and Joel Dollaga for mouse management. The research reported in this article was supported by the National Institutes of Health (5 T32 AI07290 to M.A.I. and J.W.F.; R01HL058770, R01CA86085, and U01HL09999 to I.L.W.), the California Institute for Stem Cell Research (T1-00001 to M.A.I. and J.S.; RT2-02060 to I.L.W.), the Harvard Stem Cell Institute (to T.S.), the Siebel Stem Cell Institute and the Thomas and Stacey Siebel Foundation (to I.K.D.), and the Virginia and D.K. Ludwig Fund for Cancer Research (to I.L.W.). NR 47 TC 16 Z9 16 U1 2 U2 5 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 APR 8 PY 2014 VL 2 IS 4 BP 457 EP 472 DI 10.1016/j.stemcr.2014.02.001 PG 16 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1XP UT WOS:000336648800007 PM 24749071 ER PT J AU Jung, Y Ng, JH Keating, CP Senthil-Kumar, P Zhao, J Randolph, MA Winograd, JM Evans, CL AF Jung, Yookyung Ng, Joanna H. Keating, Cameron P. Senthil-Kumar, Prabhu Zhao, Jie Randolph, Mark A. Winograd, Jonathan M. Evans, Conor L. TI Comprehensive Evaluation of Peripheral Nerve Regeneration in the Acute Healing Phase Using Tissue Clearing and Optical Microscopy in a Rodent Model SO PLOS ONE LA English DT Article ID RAMAN SCATTERING MICROSCOPY; IN-VIVO; SCIATIC-NERVE; INJURY; RAT; SYSTEM; REPAIR; IMPROVES; 3DISCO; ORGANS AB Peripheral nerve injury (PNI), a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout nerves in a PNI model. The methods developed in this study could advance PNI research allowing both researchers and clinicians to further understand the individual events of axonal degeneration and regeneration on a multifaceted level. C1 [Jung, Yookyung; Zhao, Jie; Evans, Conor L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. [Ng, Joanna H.; Keating, Cameron P.; Senthil-Kumar, Prabhu; Randolph, Mark A.; Winograd, Jonathan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg,Plast Surg Res Lab, Boston, MA USA. RP Evans, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. EM Evans.Conor@mgh.harvard.edu FU American Society for Surgery of the Hand (Basic Science Grant); Department of Defense "Center for Integration of Medicine and Innovative Technology" (CIMIT) [W81XWH-09-2-0001]; National Institutes of Heath (NIH) Innovative Molecular Analysis Technologies (IMAT) program [R21 CA155535]; NIH Director's New Innovator Award [DP2 OD007096] FX This research was supported by the American Society for Surgery of the Hand (Basic Science Grant, www.assh.org), the Department of Defense "Center for Integration of Medicine and Innovative Technology" (CIMIT, www.cimit.org) Grant Award #W81XWH-09-2-0001, the National Institutes of Heath (NIH) Innovative Molecular Analysis Technologies (IMAT, imat.cancer.gov) program, grant number R21 CA155535, and the NIH Director's New Innovator Award, grant number DP2 OD007096. Information on the New Innovator Award Program is at http://nihroadmap.nih.gov/newinnovator/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 10 Z9 10 U1 0 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 APR 8 PY 2014 VL 9 IS 4 AR e94054 DI 10.1371/journal.pone.0094054 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE7FA UT WOS:000334160900076 PM 24714405 ER PT J AU Keefe, CC Goldman, MM Zhang, K Clarke, N Reitz, RE Welt, CK AF Keefe, Candace C. Goldman, Mildred M. Zhang, Ke Clarke, Nigel Reitz, Richard E. Welt, Corrine K. TI Simultaneous Measurement of Thirteen Steroid Hormones in Women with Polycystic Ovary Syndrome and Control Women Using Liquid Chromatography-Tandem Mass Spectrometry SO PLOS ONE LA English DT Article ID ANDROGEN OVERPRODUCTION; THECA CELLS; TESTOSTERONE; CATHETERIZATION; HIRSUTISM; RESPONSES; EXCESS; MILIEU; PCOS AB Background: The measurement of adrenal and ovarian androgens in women with PCOS has been difficult based on poor specificity and sensitivity of assays in the female range. Methods: Women with PCOS (NIH criteria; n = 52) and control subjects with 25-35 day menstrual cycles, no evidence of hyperandrogenism and matched for BMI (n = 42) underwent morning blood sampling. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to simultaneously measure 13 steroids from a single blood sample to measure adrenal and ovarian steroids. Androgen and progesterone results were compared in the same samples using RIA. Results: Testosterone, androstenedione, progesterone and 17OH progesterone levels were higher when measured using RIA compared to LC-MS/MS, although the testosterone RIA demonstrated the best agreement with the LC-MS/MS using a Bland-Altman analysis. Results using LC-MS/MS demonstrated that the concentration of androgens and their precursors were higher in women with PCOS than controls [median (2.5, 97.5th % ile); 1607 (638, 3085) vs. 1143 (511, 4784) ng/dL; p = 0.03]. Women with PCOS had higher testosterone [49 (16, 125) vs. 24 (10, 59) ng/dL], androstenedione [203 (98, 476) vs. 106 (69, 223) ng/dL] and 17OH progesterone levels [80 (17, 176) vs. 44 (17, 142) ng/dL] compared to controls (all P<0.02), but no differences in serum concentrations of the adrenal steroids DHEAS, cortisol, corticosterone and their 11 deoxy precursors. Women with PCOS also had an increase in the product: precursor ratio for 3 beta-hydroxysteroid dehydrogenase [22% (6, 92) vs. 20% (4, 43); p = 0.009]. Conclusion: LC-MS/MS was superior to RIA in measuring androstenedione, progesterone and 17OH progesterone levels, while testosterone measurements were better matched in the two assays. Androgen levels were higher in women with PCOS in the absence of a difference in adrenal-predominant steroids. These data support previous findings that the ovary is an important source for the androgen excess in women with PCOS. C1 [Keefe, Candace C.; Welt, Corrine K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Goldman, Mildred M.; Zhang, Ke; Clarke, Nigel; Reitz, Richard E.] Quest Diagnost Nichols Inst, Steroids Dept, San Juan Capistrano, CA USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU National Institutes of Health [1R01HD065029, ADA 1-10-CT-57, 1 UL1 RR025758] FX Funding came from the National Institutes of Health 1R01HD065029 (CKW), ADA 1-10-CT-57 (CKW) and the 1 UL1 RR025758 Harvard Clinical and Translational Science Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 19 Z9 20 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 APR 8 PY 2014 VL 9 IS 4 AR e93805 DI 10.1371/journal.pone.0093805 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE7FA UT WOS:000334160900049 PM 24713888 ER PT J AU Rose, J Augestad, KM Kong, CY Meropol, NJ Kattan, MW Hong, QQ An, XB Cooper, GS AF Rose, Johnie Augestad, Knut Magne Kong, Chung Yin Meropol, Neal J. Kattan, Michael W. Hong, Qingqing An, Xuebei Cooper, Gregory S. TI A simulation model of colorectal cancer surveillance and recurrence SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Colorectal cancer; Recurrence; Surveillance; Follow-up; Model ID COST-EFFECTIVENESS ANALYSIS; FOLLOW-UP; COLON-CANCER; CURATIVE RESECTION; CARCINOEMBRYONIC ANTIGEN; MEDICARE POPULATION; PRACTICE GUIDELINE; HEPATIC RESECTION; DECISION-ANALYSIS; RECTAL-CANCER AB Background: Approximately one-third of those treated curatively for colorectal cancer (CRC) will experience recurrence. No evidence-based consensus exists on how best to follow patients after initial treatment to detect asymptomatic recurrence. Here, a new approach for simulating surveillance and recurrence among CRC survivors is outlined, and development and calibration of a simple model applying this approach is described. The model's ability to predict outcomes for a group of patients under a specified surveillance strategy is validated. Methods: We developed an individual-based simulation model consisting of two interacting submodels: a continuous-time disease-progression submodel overlain by a discrete-time Markov submodel of surveillance and re-treatment. In the former, some patients develops recurrent disease which probabilistically progresses from detectability to unresectability, and which may produce early symptoms leading to detection independent of surveillance testing. In the latter submodel, patients undergo user-specified surveillance testing regimens. Parameters describing disease progression were preliminarily estimated through calibration to match five-year disease-free survival, overall survival at years 1-5, and proportion of recurring patients undergoing curative salvage surgery from one arm of a published randomized trial. The calibrated model was validated by examining its ability to predict these same outcomes for patients in a different arm of the same trial undergoing less aggressive surveillance. Results: Calibrated parameter values were consistent with generally observed recurrence patterns. Sensitivity analysis suggested probability of curative salvage surgery was most influenced by sensitivity of carcinoembryonic antigen assay and of clinical interview/examination (i.e. scheduled provider visits). In validation, the model accurately predicted overall survival (59% predicted, 58% observed) and five-year disease-free survival (55% predicted, 53% observed), but was less accurate in predicting curative salvage surgery (10% predicted; 6% observed). Conclusions: Initial validation suggests the feasibility of this approach to modeling alternative surveillance regimens among CRC survivors. Further calibration to individual-level patient data could yield a model useful for predicting outcomes of specific surveillance strategies for risk-based subgroups or for individuals. This approach could be applied toward developing novel, tailored strategies for further clinical study. It has the potential to produce insights which will promote more effective surveillance-leading to higher cure rates for recurrent CRC. C1 [Rose, Johnie; Meropol, Neal J.; Hong, Qingqing; An, Xuebei; Cooper, Gregory S.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Rose, Johnie; Meropol, Neal J.; Cooper, Gregory S.] Case Comprehens Canc Ctr, Cleveland, OH USA. [Augestad, Knut Magne] Univ Hosp North Norway, Norwegian Natl Ctr Telemed & Integrated Car, Tromso, Norway. [Kong, Chung Yin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meropol, Neal J.; Cooper, Gregory S.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Kattan, Michael W.] Cleveland Clin, Cleveland, OH 44106 USA. RP Rose, J (reprint author), Case Western Reserve Univ, Sch Med, 11000 Cedar Ave,Ste 402, Cleveland, OH 44106 USA. EM johnie.rose@case.edu FU National Cancer Institute Program Grant [5P30 CA043703-21]; American Cancer Society [MRSG-13-315-01-CPHPS]; Mentored Research Scholar Grant in Applied and Clinical Research FX JR, NJM, MWK, and GSC were supported for this work in part by a National Cancer Institute Program Grant (5P30 CA043703-21). JR was supported by a Mentored Research Scholar Grant in Applied and Clinical Research, MRSG-13-315-01-CPHPS from the American Cancer Society. The funders played no role in the study design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 66 TC 3 Z9 3 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD APR 8 PY 2014 VL 14 AR 29 DI 10.1186/1472-6947-14-29 PG 13 WC Medical Informatics SC Medical Informatics GA AF2PR UT WOS:000334554500001 PM 24708517 ER PT J AU Dehmer, GJ Drozda, JP Brindis, RG Masoudi, FA Rumsfeld, JS Slattery, LE Oetgen, WJ AF Dehmer, Gregory J. Drozda, Joseph P., Jr. Brindis, Ralph G. Masoudi, Frederick A. Rumsfeld, John S. Slattery, Lara E. Oetgen, William J. TI Public Reporting of Clinical Quality Data An Update for Cardiovascular Specialists SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE healthcare reform; outcomes; public reporting; quality ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; WISCONSIN PHYSICIAN GROUPS; ADMINISTRATIVE DATA; PERFORMANCE REPORTS; CARDIAC-SURGERY; CLAIMS DATA; OF-CARE; OUTCOMES; MORTALITY AB Public reporting of hospital and individual provider quality of care measures is not a new concept. In the United States, the first national public reports of hospital mortality data occurred in 1986, and detailed physician-level data for cardiac surgery are now reported in 4 states. The development of the "Hospital Compare," and more recently, the " Physician Compare" websites has further expanded public reporting for hospitals and providers. Several professional organizations, including the American Medical Association, Society of Thoracic Surgeons, and the American College of Cardiology, have published policy statements articulating key principles to guide the public reporting process. Despite the rapid proliferation of public reporting efforts, more research is needed to better define meaningful measures to report and fully understand the impact of public reporting on healthcare delivery. (C) 2014 by the American College of Cardiology Foundation C1 [Dehmer, Gregory J.] Baylor Scott & White Hlth, Div Cardiol, Texas A&M Hlth Sci Ctr, Temple, TX 76508 USA. [Drozda, Joseph P., Jr.] Mercy Hlth, Chesterfield, MO USA. [Brindis, Ralph G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Brindis, Ralph G.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [Masoudi, Frederick A.] Univ Colorado, Div Cardiol, Aurora, CO USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Slattery, Lara E.; Oetgen, William J.] Amer Coll Cardiol, Washington, DC USA. [Oetgen, William J.] Georgetown Univ, Dept Med, Washington, DC USA. RP Dehmer, GJ (reprint author), Baylor Scott & White Hlth, Cardiol Div MS 33 ST156, 2401 South 31st St, Temple, TX 76508 USA. EM gdehmer@sw.org NR 56 TC 20 Z9 22 U1 0 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 APR 8 PY 2014 VL 63 IS 13 BP 1239 EP 1245 DI 10.1016/j.jacc.2013.11.050 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE2LK UT WOS:000333804300003 PM 24509280 ER PT J AU Raal, FJ Giugliano, RP Sabatine, MS Koren, MJ Langslet, G Bays, H Blom, D Eriksson, M Dent, R Wasserman, SM Huang, F Xue, A Albizem, M Scott, R Stein, EA AF Raal, Frederick J. Giugliano, Robert P. Sabatine, Marc S. Koren, Michael J. Langslet, Gisle Bays, Harold Blom, Dirk Eriksson, Mats Dent, Ricardo Wasserman, Scott M. Huang, Fannie Xue, Allen Albizem, Moetaz Scott, Rob Stein, Evan A. TI Reduction in Lipoprotein(a) With PCSK9 Monoclonal Antibody Evolocumab (AMG 145) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE dyslipidemia; evolocumab; lipoprotein(a); PCSK9 inhibition ID SUBTILISIN/KEXIN TYPE 9; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; RANDOMIZED-TRIAL; LDL CHOLESTEROL; STATIN THERAPY; RISK-FACTOR; TIMI 57 AB Objectives The purpose of this study was assess the effect of evolocumab (AMG 145) on lipoprotein (Lp)(a) from a pooled analysis of 4 phase II trials. Background Lp(a), a low-density lipoprotein (LDL) particle linked to the plasminogen-like glycoprotein apolipoprotein(a), shows a consistent and independent positive association with cardiovascular disease risk in epidemiological studies. Current therapeutic options to reduce Lp(a) are limited. Methods A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab, a fully human monoclonal antibody to PCSK9, on Lp(a), the relationship between Lp(a) and lowering of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B, and the influence of background statin therapy. Lp(a) was measured using a standardized isoform-independent method. Results Evolocumab treatment for 12 weeks resulted in significant (p < 0.001) mean (95% confidence interval) dose-related reductions in Lp(a) compared to control: 29.5% (23.3% to 35.7%) and 24.5% (20.4% to 28.7%) with 140 mg and 420 mg, dosed every 2 and 4 weeks, respectively, with no plateau of effect. Lp(a) reductions were significantly correlated with percentages of reductions in LDL-C (Spearman correlation coefficient, 0.5134; p < 0.001) and apolipoprotein B (Spearman correlation coefficient, 0.5203; p < 0.001). Mean percentage reductions did not differ based on age or sex but the trend was greater in those patients taking statins. Conclusions Inhibition of PCSK9 with evolocumab resulted in significant dose- related reductions in Lp(a). While the mean percentage of reduction was significantly greater in those patients with baseline Lp(a) of >= 125 nmol/l, the absolute reduction was substantially larger in those with levels >125 nmol/l. (C) 2014 by the American College of Cardiology Foundation C1 [Raal, Frederick J.] Univ Witwatersrand, Fac Hlth Sci, Carbohydrate & Lipid Metab Res Unit, Johannesburg, South Africa. [Giugliano, Robert P.; Sabatine, Marc S.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Koren, Michael J.] Jacksonville Ctr Clin Res, Jacksonville, FL USA. [Langslet, Gisle] Oslo Univ Hosp, Lipid Clin, Oslo, Norway. [Bays, Harold] Louisville Metab & Atherosclerosis Res Ctr, Louisville, KY USA. [Blom, Dirk] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. [Eriksson, Mats] Karolinska Univ Hosp, Stockholm, Sweden. [Dent, Ricardo; Wasserman, Scott M.; Huang, Fannie; Xue, Allen; Albizem, Moetaz; Scott, Rob] Amgen Inc, Thousand Oaks, CA 91320 USA. [Stein, Evan A.] EVLIN Consultants, Chicago, IL USA. RP Stein, EA (reprint author), Metab & Atherosclerosis Res Ctr, 5355 Medspace Way, Cincinnati, OH USA. EM esteinmrl@aol.com FU Amgen, Inc.; Sanofi; TIMI Study Group; Amgen; Daiichi- Sankyo FX This study was funded by Amgen, Inc. Dr. Raal has received consulting fees from Amgen, Inc., and Sanofi related to PCSK9 inhibitors; and his institution has received research funding related to PCSK9 inhibitor clinical trials from Amgen, Inc., and Sanofi. Dr. Giugliano has received honoraria for consulting and CME lectures from Amgen, Daiichi Sankyo, Bristol- Myers Squibb, Merck, Regeneron, and Sanofi; and participates in lipid research as a member of the TIMI Study Group, which has received research grant support for clinical trials from Amgen, Daiichi- Sankyo, and Merck. Dr. Sabatine has received grant support through Brigham and Women's Hospital from Amgen, AstraZeneca, AstraZeneca/Bristol-Myers Squibb Alliance, Bristol-Myers Squibb/Sanofi Joint Venture, Daiichi Sankyo, Eisai, Genzyme, GlaxoSmithKline, Merck, Sanofi, Takeda, Abbott Laboratories, Accumetrics, Critical Diagnostics, Nanosphere, and Roche Diagnostics; and has consulted for Aegerion, Amgen, Diasorin, GlaxoSmithKline, Merck, Pfizer, Sanofi, AstraZeneca, and Vertex. Dr. Koren is an employee of Jacksonville Center for Clinical Research, which has received grants from Amgen Inc. Dr. Langslet is a consultant for and advisory board member of Janssen Pharmaceutical. Dr. Bays has consulted for and received speaker fees from Amarin, Amgen, AstraZeneca, Bristol- Myers Squibb, Catabasis, Daiichi Sankyo, Eisai Merck, VIVUS, and WBL Biotech Co.; and his research site has received grants from Alere, Amarin, Amgen, Ardea, AstraZeneca, Boehringer Ingelheim, BristolMyers Squibb, California Raisin Board, Catabasis, Eisai, Elcelyx, Eli Lilly, Esperion, Essentialis, Forest, Gilead, Given, GlaxoSmithKline, High Point Pharmaceuticals LLC, Hoffman LaRoche, Home Access, Janssen, Merck, Micropharma Limited, Necktar, Novartis, Novo Nordisk, Omthera, Orexigen, Pfizer, Pronova, Regeneron, Stratum Nutrition, Takeda, TIMI, Transtech Pharma, Trygg, VIVUS, WBL Biotech Co., and Xoma. Dr. Blom has received consulting fees from Amgen Inc. and Sanofi related to PCSK9 inhibitors; has served on advisory boards of Amgen, Sanofi, Aegerion, and Merck, Sharpe, Dohme; has received speaker honoraria from Amgen, Aegerion, Merck, Sharpe, Dohme, Unilever, Pfizer, AstraZeneca, Ranbaxy, PharmaDynamics, and Sanofi; and his institution has received research funding related to PCSK9 inhibitor clinical trials from Amgen, Inc., and Sanofi. Dr. Eriksson has received lecture fees from Merck, Sharpe, Dohme and AstraZeneca and consulting fees from Amgen, Sanofi, and Novo Nordisk. Drs. Dent, Wasserman, Huang, Xue, Albizem, and Scott are employees of Amgen, Inc., and have received Amgen stock/stock options. Dr. Stein has received consulting fees from Amgen Inc., Adnexus Therapeutics/Bristol- Myers Squibb, Genentech/Roche, and Regeneron/Sanofi related to PCSK9 inhibitors. NR 34 TC 101 Z9 102 U1 3 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 8 PY 2014 VL 63 IS 13 BP 1278 EP 1288 DI 10.1016/j.jacc.2014.01.006 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE2LK UT WOS:000333804300009 PM 24509273 ER PT J AU Hu, SN Yonetsu, T Jia, HB Karanasos, A Aguirre, AD Tian, JW Abtahian, F Vergallo, R Soeda, T Lee, H McNulty, I Kato, K Yu, B Mizuno, K Toutouzas, K Stefanadis, C Jang, IK AF Hu, Sining Yonetsu, Taishi Jia, Haibo Karanasos, Antonios Aguirre, Aaron D. Tian, Jinwei Abtahian, Farhad Vergallo, Rocco Soeda, Tsunenari Lee, Hang McNulty, Iris Kato, Koji Yu, Bo Mizuno, Kyoichi Toutouzas, Konstantinos Stefanadis, Christodoulos Jang, Ik-Kyung TI Residual Thrombus Pattern in Patients With ST-Segment Elevation Myocardial Infarction Caused by Plaque Erosion Versus Plaque Rupture After Successful Fibrinolysis An Optical Coherence Tomography Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID LESIONS C1 [Hu, Sining; Jia, Haibo; Tian, Jinwei; Yu, Bo] Harbin Med Univ, Key Lab Myocardial Ischemia, Affiliated Hosp 2, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China. [Hu, Sining; Yonetsu, Taishi; Jia, Haibo; Tian, Jinwei; Abtahian, Farhad; Vergallo, Rocco; Soeda, Tsunenari; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Karanasos, Antonios; Toutouzas, Konstantinos; Stefanadis, Christodoulos] Hippokrateion Hosp, Athens Med Sch, Dept Cardiol 1, Athens, Greece. [Aguirre, Aaron D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kato, Koji; Mizuno, Kyoichi] Nippon Med Sch, Dept Cardiovasc Med, Tokyo 113, Japan. RP Yu, B (reprint author), Harbin Med Univ, Key Lab Myocardial Ischemia, Affiliated Hosp 2, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China. EM yubodr@163.com; ijang@partners.org NR 5 TC 5 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 8 PY 2014 VL 63 IS 13 BP 1336 EP 1338 DI 10.1016/j.jacc.2013.11.025 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AE2LK UT WOS:000333804300020 PM 24361315 ER PT J AU Cacciatore, S Luchinat, C Tenori, L AF Cacciatore, Stefano Luchinat, Claudio Tenori, Leonardo TI Knowledge discovery by accuracy maximization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dissimilarity matrix; mapping; multivariate statistics; clustering; data visualization ID NONLINEAR DIMENSIONALITY REDUCTION; GENE-EXPRESSION DATA; CLUSTER-ANALYSIS; CLASSIFICATION; CANCER AB Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold's topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan's presidency and not from its beginning. C1 [Cacciatore, Stefano; Luchinat, Claudio] Univ Florence, Magnet Resonance Ctr CERM, I-50019 Sesto Fiorentino, Italy. [Cacciatore, Stefano; Luchinat, Claudio] Univ Florence, Dept Chem, I-50019 Sesto Fiorentino, Italy. [Cacciatore, Stefano] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cacciatore, Stefano] Univ Rovira & Virgili, Spanish Biomed Res Ctr Diabet & Associated Disord, Metabol Platform, E-43007 Tarragona, Spain. [Luchinat, Claudio; Tenori, Leonardo] FiorGen Fdn, I-50019 Sesto Fiorentino, Italy. RP Luchinat, C (reprint author), Univ Florence, Magnet Resonance Ctr CERM, I-50019 Sesto Fiorentino, Italy. EM luchinat@cerm.unifi.it RI Tenori, Leonardo/J-9258-2016; OI Tenori, Leonardo/0000-0001-6438-059X; Cacciatore, Stefano/0000-0001-7052-7156; Luchinat, Claudio/0000-0003-2271-8921 FU European Commission [312941, 261572, 266331, 284209]; Programmi di Ricerca Nazionale [2009FAKHZT_001]; Fondazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Ricerca sul Cancro FX We thank S. Tyekucheva, A. K. Smilde, E. Saccenti, C. Sander, and M. A. Andrade-Navarro for support and several critical discussions. We also thank E. Emsellem for expressing interest in our analysis of the early-type galaxies datasets, and the anonymous reviewer of the earlier versions of this manuscript for the many constructive criticisms and suggestions that allowed us to significantly improve the paper. This work was partly supported by the European Commission-funded FP7 projects COSMOS (312941), WeNMR (261572), CHANCE (266331), BioMedBridges (284209), and by the Programmi di Ricerca Nazionale (2009FAKHZT_001). S.C. was supported by a fellowship from Fondazione Italiana per la Ricerca sul Cancro. NR 45 TC 9 Z9 9 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 8 PY 2014 VL 111 IS 14 BP 5117 EP 5122 DI 10.1073/pnas.1220873111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200030 PM 24706821 ER PT J AU Macdonald, LE Karow, M Stevens, S Auerbach, W Poueymirou, WT Yasenchak, J Frendewey, D Valenzuela, DM Giallourakis, CC Alt, FW Yancopoulos, GD Murphy, AJ AF Macdonald, Lynn E. Karow, Margaret Stevens, Sean Auerbach, Wojtek Poueymirou, William T. Yasenchak, Jason Frendewey, David Valenzuela, David M. Giallourakis, Cosmas C. Alt, Frederick W. Yancopoulos, George D. Murphy, Andrew J. TI Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genome engineering; therapeutic antibody; immunoglobulin locus ID MEDIATED CASSETTE EXCHANGE; HUMAN-ANTIBODIES; ESCHERICHIA-COLI; TRANSGENIC MICE; KAPPA LOCUS; IGH LOCUS; CRE-LOXP; CELLS; RECOMBINATION; EXPRESSION AB Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and. light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice. C1 [Macdonald, Lynn E.; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T.; Yasenchak, Jason; Frendewey, David; Valenzuela, David M.; Yancopoulos, George D.; Murphy, Andrew J.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Giallourakis, Cosmas C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. [Giallourakis, Cosmas C.; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Giallourakis, Cosmas C.; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Giallourakis, Cosmas C.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Yancopoulos, GD (reprint author), Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA. EM george@regeneron.com; andrew.murphy@regeneron.com OI Frendewey, David/0000-0003-2305-3490; Murphy, Andrew/0000-0003-4152-4081 FU Howard Hughes Medical Institute; NIDDK NIH HHS [P30 DK043351] NR 44 TC 20 Z9 20 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 APR 8 PY 2014 VL 111 IS 14 BP 5147 EP 5152 DI 10.1073/pnas.1323896111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200035 PM 24706858 ER PT J AU Chen, EY Deran, MT Ignatius, MS Grandinetti, KB Clagg, R McCarthy, KM Lobbardi, RM Brockmann, J Keller, C Wu, X Langenau, DM AF Chen, Eleanor Y. DeRan, Michael T. Ignatius, Myron S. Grandinetti, Kathryn Brooke Clagg, Ryan McCarthy, Karin M. Lobbardi, Riadh M. Brockmann, Jillian Keller, Charles Wu, Xu Langenau, David M. TI Glycogen synthase kinase 3 inhibitors induce the canonical WNT/beta-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CANCER STEM-CELLS; IN-VITRO; DIFFERENTIATION; WNT; ACTIVATION; LEUKEMIA; THERAPY; VIVO; PHOSPHORYLATION; GLIOBLASTOMA AB Embryonal rhabdomyosarcoma (ERMS) is a common pediatric malignancy of muscle, with relapse being the major clinical challenge. Self-renewing tumor-propagating cells (TPCs) drive cancer relapse and are confined to a molecularly definable subset of ERMS cells. To identify drugs that suppress ERMS self-renewal and induce differentiation of TPCs, a large-scale chemical screen was completed. Glycogen synthase kinase 3 (GSK3) inhibitors were identified as potent suppressors of ERMS growth through inhibiting proliferation and inducing terminal differentiation of TPCs into myosin-expressing cells. In support of GSK3 inhibitors functioning through activation of the canonical WNT/beta-catenin pathway, recombinant WNT3A and stabilized beta-catenin also enhanced terminal differentiation of human ERMS cells. Treatment of ERMS-bearing zebrafish with GSK3 inhibitors activated the WNT/beta-catenin pathway, resulting in suppressed ERMS growth, depleted TPCs, and diminished self-renewal capacity in vivo. Activation of the canonical WNT/beta-catenin pathway also significantly reduced self-renewal of human ERMS, indicating a conserved function for this pathway in modulating ERMS self-renewal. In total, we have identified an unconventional tumor suppressive role for the canonical WNT/beta-catenin pathway in regulating self-renewal of ERMS and revealed therapeutic strategies to target differentiation of TPCs in ERMS. C1 [Chen, Eleanor Y.; Ignatius, Myron S.; Clagg, Ryan; McCarthy, Karin M.; Lobbardi, Riadh M.; Brockmann, Jillian; Langenau, David M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chen, Eleanor Y.; Ignatius, Myron S.; Clagg, Ryan; McCarthy, Karin M.; Lobbardi, Riadh M.; Brockmann, Jillian; Langenau, David M.] Massachusetts Gen Hosp, Dept Regenerat Med, Boston, MA 02114 USA. [Chen, Eleanor Y.; Ignatius, Myron S.; Clagg, Ryan; McCarthy, Karin M.; Lobbardi, Riadh M.; Brockmann, Jillian; Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Chen, Eleanor Y.; DeRan, Michael T.; Ignatius, Myron S.; Clagg, Ryan; McCarthy, Karin M.; Lobbardi, Riadh M.; Wu, Xu; Langenau, David M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [DeRan, Michael T.; Wu, Xu] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Grandinetti, Kathryn Brooke] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. [Keller, Charles] Pape Family Pediat Res Inst, Dept Pediat, Pediat Canc Biol Program, Portland, OR 97239 USA. RP Wu, X (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM xwu@cbrc2.mgh.harvard.edu; dlangenau@mgh.harvard.edu FU National Institutes of Health [R01CA154923, R01CA143082, R21CA156056, U54CA168512, K08AR063165, K99CA175184]; Alex's Lemonade Stand Foundation; Sarcoma Foundation of America; Massachusetts General Hospital Howard Goodman Fellowship; Harvard Stem Cell Institute; Steward Rahl-Melanoma Research Alliance Young Investigator Award; American Cancer Society Research Scholar Award; St. Baldrick's Foundation Scholar Award; Genomics Institute of the Novartis Research Foundation postdoctoral fellowship; Massachusetts General Hospital Toteson Fund for Medical Discovery FX This work was supported by grants from the National Institutes of Health including R01CA154923 (to D. M. L.), R01CA143082 (to C. K.), R21CA156056 (to D. M. L.), U54CA168512, K08AR063165 (to E.Y.C.), and K99CA175184 (to M. S. I.). Additional support was provided by the Alex's Lemonade Stand Foundation (D. M. L. and M. S. I.), the Sarcoma Foundation of America (D. M. L.), the Massachusetts General Hospital Howard Goodman Fellowship (D. M. L.), the Harvard Stem Cell Institute (D. M. L. and X. W.), the Steward Rahl-Melanoma Research Alliance Young Investigator Award (X. W.), the American Cancer Society Research Scholar Award (X. W.), the St. Baldrick's Foundation Scholar Award (E.Y.C.), the Genomics Institute of the Novartis Research Foundation postdoctoral fellowship (K. B. G.), and the Massachusetts General Hospital Toteson Fund for Medical Discovery (M.S.I.). NR 39 TC 32 Z9 35 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 8 PY 2014 VL 111 IS 14 BP 5349 EP 5354 DI 10.1073/pnas.1317731111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200069 PM 24706870 ER PT J AU Boisvert, H Lorand, L Duncan, MJ AF Boisvert, Heike Lorand, Laszlo Duncan, Margaret J. TI Transglutaminase 2 is essential for adherence of Porphyromonas gingivalis to host cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; GINGIPAIN ADHESIN PEPTIDE; BETA-SANDWICH DOMAIN; TISSUE TRANSGLUTAMINASE; EPITHELIAL-CELLS; PERIODONTAL-DISEASE; FIBRONECTIN; BINDING; FIMBRIAE; SURFACE AB Porphyromonas gingivalis is the major causative agent of periodontitis, and it may also be involved in the development of systemic diseases (atherosclerosis, rheumatoid arthritis). P. gingivalis is found on and within oral and gingival epithelial cells following binding to surface components of host cells, which serve as receptors for the bacterium. Evidence is presented in this study that shows that transglutaminase 2 (TG2) plays a critical role in the adherence of P. gingivalis to host cells. Studies of confocal microscopy indicate colocalization of P. gingivalis with TG2 on the surface of HEp-2 epithelial cells, with clusters of TG2 seen at bacterial attachment sites. By silencing the expression of TG2 with siRNA in HEp-2 cells, P. gingivalis association was greatly diminished. The bacterium does not bind well to a mouse fibroblast cell line that produces low amounts of surface TG2, but binding can be restored by introduction of TG2 expressed on a plasmid. TG2 can form very tight complexes with fibronectin (FN), and the complementary binding sites of the two proteins are known. A synthetic peptide that mimics the main FN-binding sequence of TG2 blocks the formation of TG2-FN complexes and is highly effective in inhibiting adherence of P. gingivalis to host cells. These findings provide evidence of a role for cell-surface TG2 in bacterial attachment and subsequent internalization. C1 [Boisvert, Heike; Duncan, Margaret J.] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. [Lorand, Laszlo] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA. RP Boisvert, H (reprint author), Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. EM hboisvert@forsyth.org; l-lorand@northwestern.edu FU US National Institutes of Health [R01-DE015931, R03-DE023129] FX We thank Dr. Alexey Belkin for the NIH/3T3 pGeneTG2 and control cell lines and his invaluable advice. This work was supported by US National Institutes of Health Grants R01-DE015931 (to M.J.D.) and R03-DE023129 (to H.B.). NR 51 TC 1 Z9 1 U1 1 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 APR 8 PY 2014 VL 111 IS 14 BP 5355 EP 5360 DI 10.1073/pnas.1402740111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE4VU UT WOS:000333985200070 PM 24706840 ER PT J AU Palevsky, PM AF Palevsky, Paul M. TI Renal Angina: Right Concept... Wrong Name? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material DE AKI; biomarkers; diagnosis ID ACUTE KIDNEY INJURY; BIOMARKERS C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Univ Dr,Room 7E123,111F-U, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 12 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR 7 PY 2014 VL 9 IS 4 BP 633 EP 634 DI 10.2215/CJN.01520214 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AE2XM UT WOS:000333836600001 PM 24677556 ER PT J AU Pendergraft, WF Cortazar, FB Wenger, J Murphy, AP Rhee, EP Laliberte, KA Niles, JL AF Pendergraft, William F., III Cortazar, Frank B. Wenger, Julia Murphy, Andrew P. Rhee, Eugene P. Laliberte, Karen A. Niles, John L. TI Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ANTIBODY-ASSOCIATED VASCULITIS; CYCLOPHOSPHAMIDE; GRANULOMATOSIS; POLYANGIITIS; PATHOGENESIS AB Background and objectivesRemission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission.Design, setting, participants, & measurementsA retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined.ResultsIn the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase-ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population.ConclusionThis analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. C1 [Pendergraft, William F., III] Brigham & Womens Hosp, Joint Nephrol Fellowship Program, Boston, MA 02115 USA. [Pendergraft, William F., III] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pendergraft, William F., III; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Pendergraft, William F., III; Murphy, Andrew P.; Laliberte, Karen A.; Niles, John L.] Massachusetts Gen Hosp, Vasculitis & Glomerulonephritis Clin, Div Nephrol, Boston, MA 02114 USA. [Cortazar, Frank B.] Massachusetts Gen Hosp, Categor Internal Med Residency Program, Dept Med, Boston, MA 02114 USA. RP Niles, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 151 Merrimac St,Floor 3, Boston, MA 02114 USA. EM jlniles@partners.org FU Alexion Pharmaceuticals FX J.L.N. has served as a rituximab-specific advisory board member for Genentech, is currently participating in the Genentech-sponsored Rituximab in ANCA-Associated Vasculitis Registry (RAVER) study, and is receiving clinical research funding from Alexion Pharmaceuticals. NR 21 TC 26 Z9 27 U1 1 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR 7 PY 2014 VL 9 IS 4 BP 736 EP 744 DI 10.2215/CJN.07340713 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AE2XM UT WOS:000333836600017 PM 24626432 ER PT J AU Little, MH Brown, D Humphreys, BD McMahon, AP Miner, JH Sands, JM Weisz, OA Mullins, C Hoshizaki, D AF Little, Melissa H. Brown, Dennis Humphreys, Benjamin D. McMahon, Andrew P. Miner, Jeffrey H. Sands, Jeff M. Weisz, Ora A. Mullins, Chris Hoshizaki, Deborah CA KRND TI Defining Kidney Biology to Understand Renal Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article AB The Kidney Research National Dialogue represents a novel effort by the National Institute of Diabetes and Digestive and Kidney Diseases to solicit and prioritize research objectives from the renal research and clinical communities. The present commentary highlights selected scientific opportunities specific to the study of renal development, physiology, and cell biology. Describing such fundamental kidney biology serves as a necessary foundation for translational and clinical studies that will advance disease care and prevention. It is intended that these objectives foster and focus scientific efforts in these areas in the coming decade and beyond. C1 [Little, Melissa H.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. [Brown, Dennis] Harvard Univ, Massachussetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Brown, Dennis] Harvard Univ, Massachussetts Gen Hosp, Program Membrane Biol, Boston, MA 02115 USA. [Brown, Dennis] Harvard Univ, Massachussetts Gen Hosp, Div Nephrol, Boston, MA 02115 USA. [Humphreys, Benjamin D.] Harvard Univ, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [McMahon, Andrew P.] Univ So Calif, Los Angeles, CA USA. [Miner, Jeffrey H.] Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA. [Sands, Jeff M.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Sands, Jeff M.] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA. [Weisz, Ora A.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Mullins, Chris; Hoshizaki, Deborah] NIDDK, NIH, Bethesda, MD 20892 USA. RP Hoshizaki, D (reprint author), NIDDK, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM DKHOSH@NIH.GOV RI Little, Melissa/A-6170-2010 OI Little, Melissa/0000-0003-0380-2263 FU Evotec FX B.D.H. is funded by a grant from Evotec with the goal of discovering new therapeutic targets to treat acute kidney disease and CKD. A.P.M. is in collaboration around kidney disease with Evotec, for which the laboratory of A.P.M. receives research support from Evotec. NR 1 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR 7 PY 2014 VL 9 IS 4 BP 809 EP 811 DI 10.2215/CJN.10851013 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AE2XM UT WOS:000333836600026 PM 24370769 ER PT J AU Stegmaier, K AF Stegmaier, Kimberly TI Targeting Csnk1a1 in leukemia SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material C1 [Stegmaier, Kimberly] Dana Farber Canc Inst, Boston, MA 02215 USA. [Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. RP Stegmaier, K (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM kimberly_stegmaier@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 7 PY 2014 VL 211 IS 4 BP 594 EP 594 DI 10.1084/jem.2114insight1 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AF7TJ UT WOS:000334917400001 PM 24711612 ER PT J AU Clarkson, BDS Ling, CY Shi, YJ Harris, MG Rayasam, A Sun, DD Salamat, MS Kuchroo, V Lambris, JD Sandor, M Fabry, Z AF Clarkson, Benjamin D. S. Ling, Changying Shi, Yejie Harris, Melissa G. Rayasam, Aditya Sun, Dandan Salamat, M. Shahriar Kuchroo, Vijay Lambris, John D. Sandor, Matyas Fabry, Zsuzsanna TI T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ISCHEMIC-STROKE; CEREBRAL-ISCHEMIA; IL-21; LYMPHOCYTES; REJECTION; COUNTERACTS; DYSFUNCTION; EXPRESSION; AUTOIMMUNE; DISEASE AB T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell-derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21-deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4(+) T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4(+) T cells in the area surrounding acute stroke lesions, suggesting that IL-21-mediated brain injury may be relevant to human stroke. C1 [Clarkson, Benjamin D. S.; Ling, Changying; Harris, Melissa G.; Salamat, M. Shahriar; Sandor, Matyas; Fabry, Zsuzsanna] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA. [Shi, Yejie; Sun, Dandan] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol Surg, Madison, WI 53792 USA. [Clarkson, Benjamin D. S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cellular & Mol Pathol, Madison, WI 53792 USA. [Harris, Melissa G.; Rayasam, Aditya] Univ Wisconsin, Sch Med & Publ Hlth, Neurosci Training Program, Madison, WI 53792 USA. [Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. [Kuchroo, Vijay] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Kuchroo, Vijay] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lambris, John D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Fabry, Z (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA. EM zfabry@facstaff.wisc.edu OI Lambris, John/0000-0002-9370-5776; Shi, Yejie/0000-0001-7502-9201 FU American Heart Association [12PRE12060020]; National Institutes of Health [NS037570, NS076946, AI048087, AI068730] FX This work was supported by awards from the American Heart Association (pre-doctoral fellowship # 12PRE12060020 to B. D. S. Clarkson) and the National Institutes of Health (NS037570 and NS076946 to ZF, AI048087 to M. S. Salamat, and AI068730 to J.D. Lambris). NR 30 TC 18 Z9 18 U1 4 U2 13 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 APR 7 PY 2014 VL 211 IS 4 BP 595 EP 604 DI 10.1084/jem.20131377 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AF7TJ UT WOS:000334917400002 PM 24616379 ER PT J AU Hawkes, LA Butler, PJ Frappell, PB Meir, JU Milsom, WK Scott, GR Bishop, CM AF Hawkes, Lucy A. Butler, Patrick J. Frappell, Peter B. Meir, Jessica U. Milsom, William K. Scott, Graham R. Bishop, Charles M. TI Maximum Running Speed of Captive Bar-Headed Geese Is Unaffected by Severe Hypoxia SO PLOS ONE LA English DT Article ID HIGH-ALTITUDE; BARNACLE GEESE; HEART-RATE; OXYGEN-CONSUMPTION; BRANTA-LEUCOPSIS; EXERCISE PERFORMANCE; ENERGY-EXPENDITURE; AYTHYA-FULIGULA; ANSER-INDICUS; SEA-LEVEL AB While bar-headed geese are renowned for migration at high altitude over the Himalayas, previous work on captive birds suggested that these geese are unable to maintain rates of oxygen consumption while running in severely hypoxic conditions. To investigate this paradox, we re-examined the running performance and heart rates of bar-headed geese and barnacle geese (a low altitude species) during exercise in hypoxia. Bar-headed geese (n = 7) were able to run at maximum speeds (determined in normoxia) for 15 minutes in severe hypoxia (7% O-2; simulating the hypoxia at 8500 m) with mean heart rates of 466 +/- 8 beats min(-1). Barnacle geese (n = 10), on the other hand, were unable to complete similar trials in severe hypoxia and their mean heart rate (316 beats.min(-1)) was significantly lower than bar-headed geese. In bar-headed geese, partial pressures of oxygen and carbon dioxide in both arterial and mixed venous blood were significantly lower during hypoxia than normoxia, both at rest and while running. However, measurements of blood lactate in bar-headed geese suggested that anaerobic metabolism was not a major energy source during running in hypoxia. We combined these data with values taken from the literature to estimate (i) oxygen supply, using the Fick equation and (ii) oxygen demand using aerodynamic theory for bar-headed geese flying aerobically, and under their own power, at altitude. This analysis predicts that the maximum altitude at which geese can transport enough oxygen to fly without environmental assistance ranges from 6,800 m to 8,900 m altitude, depending on the parameters used in the model but that such flights should be rare. C1 [Hawkes, Lucy A.] Bangor Univ, Sch Biol Sci, Bangor, Gwynedd, Wales. [Butler, Patrick J.] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. [Frappell, Peter B.] Univ Tasmania, Hobart, Tas, Australia. [Meir, Jessica U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Milsom, William K.] Univ British Columbia, Dept Zool, Vancouver, BC V5Z 1M9, Canada. [Scott, Graham R.] McMaster Univ, Dept Biol, Hamilton, ON, Canada. [Hawkes, Lucy A.; Bishop, Charles M.] Univ Exeter, Coll Life & Environm Sci, Penryn, Cornwall, England. RP Hawkes, LA (reprint author), Bangor Univ, Sch Biol Sci, Bangor, Gwynedd, Wales. EM l.hawkes@exeter.ac.uk OI Hawkes, Lucy/0000-0002-6696-1862 FU Biotechnology and Biological Sciences Research Council (BBSRC) of the United Kingdom [BB/F015615/1] FX The project was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) of the United Kingdom [Grant number BB/F015615/1] to CMB and PJB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 6 Z9 6 U1 6 U2 76 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 7 PY 2014 VL 9 IS 4 AR e94015 DI 10.1371/journal.pone.0094015 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE7EP UT WOS:000334159800086 PM 24710001 ER PT J AU Zhou, YL Zhang, X Klibanski, A AF Zhou, Yunli Zhang, Xun Klibanski, Anne TI Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Sporadic pituitary adenoma; Tumor suppression; Genetic mutation; Epigenetic; RB; p53 ID ARYL-HYDROCARBON-RECEPTOR; MULTIPLE ENDOCRINE NEOPLASIA; INTERACTING-PROTEIN AIP; E-CADHERIN EXPRESSION; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE MGMT; EPITHELIAL-MESENCHYMAL TRANSITION; CELL-CYCLE PROGRESSION; REPRESSES E-CADHERIN; HUMAN HEPATOCELLULAR-CARCINOMA; ONCOGENE-INDUCED SENESCENCE AB Human pituitary adenomas are the most common intracranial neoplasms. Approximately 5% of them are familial adenomas. Patients with familial tumors carry germline mutations in predisposition genes, including AIP, MEN1 and PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which therefore are caused by different mechanisms. Multiple tumor suppressive genes linked to sporadic tumors have been identified. Their inactivation is caused by epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into two groups based on their functional interaction with tumor suppressors RB or p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13, GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group includes MEG3, MGMT, PLAGL1, RASSF1, R4SSF3 and SOCSI. We propose that the tumor suppression function of these genes is mainly mediated by the RB and p53 pathways. We also discuss possible tumor suppression mechanisms for individual genes. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org FU National Institutes of Health [R01DK40947]; Guthart Family Foundation; Jarislowsky Foundation FX This work was supported by grants from the National Institutes of Health (A.K., R01DK40947), the Guthart Family Foundation, and the Jarislowsky Foundation. NR 328 TC 30 Z9 31 U1 1 U2 11 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 APR 5 PY 2014 VL 386 IS 1-2 SI SI BP 16 EP 33 DI 10.1016/j.mce.2013.09.006 PG 18 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AE5EA UT WOS:000334009400003 PM 24035864 ER PT J AU Khan, S Sallum, UW Zheng, X Nau, GJ Hasan, T AF Khan, Shazia Sallum, Ulysses W. Zheng, Xiang Nau, Gerard J. Hasan, Tayyaba TI Rapid optical determination of beta-lactamase and antibiotic activity SO BMC MICROBIOLOGY LA English DT Article DE Fluorescence; Fluorophore; Quenching; Staphylococcus; Cephalosporin; Cefazolin; beta-lactamase; beta-lactam; Antibiotic activity; Antibiotic susceptibility ID RESISTANT STAPHYLOCOCCUS-AUREUS; PENICILLIN-BINDING PROTEIN; SOFT-TISSUE INFECTIONS; MULTIPLEX PCR; ANTIMICROBIAL RESISTANCE; METHICILLIN RESISTANCE; PHOTODYNAMIC THERAPY; CEFAZOLIN THERAPY; ESCHERICHIA-COLI; GENE-EXPRESSION AB Background: The absence of rapid tests evaluating antibiotic susceptibility results in the empirical prescription of antibiotics. This can lead to treatment failures due to escalating antibiotic resistance, and also furthers the emergence of drug-resistant bacteria. This study reports a rapid optical method to detect beta-lactamase and thereby assess activity of beta-lactam antibiotics, which could provide an approach for targeted prescription of antibiotics. The methodology is centred on a fluorescence quenching based probe (beta-LEAF -beta-Lactamase Enzyme Activated Fluorophore) that mimics the structure of beta-lactam antibiotics. Results: The beta-LEAF assay was performed for rapid determination of beta-lactamase production and activity of beta-lactam antibiotic (cefazolin) on a panel of Staphylococcus aureus ATCC strains and clinical isolates. Four of the clinical isolates were determined to be lactamase producers, with the capacity to inactivate cefazolin, out of the twenty-five isolates tested. These results were compared against gold standard methods, nitrocefin disk test for beta-lactamase detection and disk diffusion for antibiotic susceptibility, showing results to be largely consistent. Furthermore, in the sub-set of beta-lactamase producers, it was demonstrated and validated that multiple antibiotics (cefazolin, cefoxitin, cefepime) could be assessed simultaneously to predict the antibiotic that would be most active for a given bacterial isolate. Conclusions: The study establishes the rapid beta-LEAF assay for beta-lactamase detection and prediction of antibiotic activity using S. aureus clinical isolates. Although the focus in the current study is beta-lactamase-based resistance, the overall approach represents a broad diagnostic platform. In the long-term, these studies form the basis for the development of assays utilizing a broader variety of targets, pathogens and drugs. C1 [Khan, Shazia; Sallum, Ulysses W.; Zheng, Xiang; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Nau, Gerard J.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Dept Med,Div Infect Dis, Ctr Vaccine Res,Sch Med, Pittsburgh, PA 15261 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU Department of Defense/Air Force Office of Research (DOD/AFOSR) [FA9550-11-1-0331]; NIH/NIBIB (National Institute of Biomedical Imaging and Bioengineering) (Point of Care Technology in Primary Care) through CIMIT (Centre for Integration of Medicine and Innovation Technology) [U54 EB015408] FX We thank Dr. Mary Jane Ferraro (Microbiology Labs, Massachusetts General Hospital, Boston, MA, USA) for very helpful discussions and for providing the S. aureus clinical isolates. We are grateful to Dr. Robert L. Skov (Statens Serum Institut, Copenhagen, Denmark) for providing some of the genotype data. We would also like to thank Dr. Akilan Palanisami and Dr. Sarika Verma for involved discussions and input, and Dr. S. Sibel Erdem for help in drawing chemical structures and proofreading. This research was funded by the Department of Defense/Air Force Office of Research (DOD/AFOSR) (Grant number FA9550-11-1-0331), and NIH/NIBIB (National Institute of Biomedical Imaging and Bioengineering) (Point of Care Technology in Primary Care) through CIMIT (Centre for Integration of Medicine and Innovation Technology) (Grant number U54 EB015408). NR 75 TC 6 Z9 6 U1 2 U2 29 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD APR 4 PY 2014 VL 14 AR 84 DI 10.1186/1471-2180-14-84 PG 14 WC Microbiology SC Microbiology GA AG4SW UT WOS:000335411600002 PM 24708478 ER PT J AU Fass, DM Schroeder, FA Perlis, RH Haggarty, SJ AF Fass, D. M. Schroeder, F. A. Perlis, R. H. Haggarty, S. J. TI EPIGENETIC MECHANISMS IN MOOD DISORDERS: TARGETING NEUROPLASTICITY SO NEUROSCIENCE LA English DT Review DE epigenetics; chromatin; neuroplasticity; experimental medicine; mood disorders ID HISTONE DEACETYLASE INHIBITORS; CHROMATIN-MEDIATED NEUROPLASTICITY; TREATMENT ENHANCEMENT PROGRAM; WEEKLY SYMPTOMATIC STATUS; PLURIPOTENT STEM-CELLS; BIPOLAR-II DEPRESSION; LONG NONCODING RNAS; GROUP PROTEIN EZH2; STAR-ASTERISK-D; DOUBLE-BLIND AB Developing novel therapeutics and diagnostic tools based upon an understanding of neuroplasticity is critical in order to improve the treatment and ultimately the prevention of a broad range of nervous system disorders. In the case of mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BPD), where diagnoses are based solely on nosology rather than pathophysiology, there exists a clear unmet medical need to advance our understanding of the underlying molecular mechanisms and to develop fundamentally new mechanism experimental medicines with improved efficacy. In this context, recent preclinical molecular, cellular, and behavioral findings have begun to reveal the importance of epigenetic mechanisms that alter chromatin structure and dynamically regulate patterns of gene expression that may play a critical role in the pathophysiology of mood disorders. Here, we will review recent advances involving the use of animal models in combination with genetic and pharmacological probes to dissect the underlying molecular mechanisms and neurobiological consequence of targeting this chromatin-mediated neuroplasticity. We discuss evidence for the direct and indirect effects of mood stabilizers, antidepressants, and antipsychotics, among their many other effects, on chromatin-modifying enzymes and on the epigenetic state of defined genomic loci, in defined cell types and in specific regions of the brain. These data, as well as findings from patient-derived tissue, have also begun to reveal alterations of epigenetic mechanisms in the pathophysiology and treatment of mood disorders. We summarize growing evidence supporting the notion that selectively targeting chromatin-modifying complexes, including those containing histone deacetylases (HDACs), provides a means to reversibly alter the acetylation state of neuronal chromatin and beneficially impact neuronal activity-regulated gene transcription and mood-related behaviors. Looking beyond current knowledge, we discuss how high-resolution, whole-genome methodologies, such as RNA-sequencing (RNA-Seq) for transcriptome analysis and chromatin immunoprecipitation-sequencing (ChIP-Seq) for analyzing genome-wide occupancy of chromatin-associated factors, are beginning to provide an unprecedented view of both specific genomic loci as well as global properties of chromatin in the nervous system. These methodologies when applied to the characterization of model systems, including those of patient-derived induced pluripotent cell (iPSC) and induced neurons (iNs), will greatly shape our understanding of epigenetic mechanisms and the impact of genetic variation on the regulatory regions of the human genome that can affect neuroplasticity. Finally, we point out critical unanswered questions and areas where additional data are needed in order to better understand the potential to target mechanisms of chromatin-mediated neuroplasticity for novel treatments of mood and other psychiatric disorders. This article is part of a Special Issue entitled: Epigenetics in Brain Function. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Fass, D. M.; Schroeder, F. A.; Haggarty, S. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fass, D. M.; Schroeder, F. A.; Haggarty, S. J.] Harvard Univ, Sch Med, Ctr Human Genet Reseach, Boston, MA 02114 USA. [Fass, D. M.; Perlis, R. H.; Haggarty, S. J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Schroeder, F. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Perlis, R. H.; Haggarty, S. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perlis, R. H.; Haggarty, S. J.] Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. RP Haggarty, SJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 185 Cambridge St, Boston, MA 02114 USA. EM haggarty@chgr.mgh.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU NIDA NIH HHS [R01 DA028301] NR 142 TC 20 Z9 21 U1 2 U2 36 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 APR 4 PY 2014 VL 264 BP 112 EP 130 DI 10.1016/j.neuroscience.2013.01.041 PG 19 WC Neurosciences SC Neurosciences & Neurology GA AD2VK UT WOS:000333093700011 PM 23376737 ER PT J AU Wang, C Schroeder, FA Hooker, JM AF Wang, C. Schroeder, F. A. Hooker, J. M. TI VISUALIZING EPIGENETICS: CURRENT ADVANCES AND ADVANTAGES IN HDAC PET IMAGING TECHNIQUES SO NEUROSCIENCE LA English DT Review DE epigenetics; chromatin; brain; imaging; probes translation ID HISTONE DEACETYLASE INHIBITION; POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE-SPECTROSCOPY; MOUSE-BRAIN; IN-VIVO; EXPRESSION; MODEL; ACETYLATION; DEPRESSION; IMPAIRMENT AB Abnormal gene regulation as a consequence of flawed epigenetic mechanisms may be central to the initiation and persistence of many human diseases. However, the association of epigenetic dysfunction with disease and the development of therapeutic agents for treatment are slow. Developing new methodologies used to visualize chromatin-modifying enzymes and their function in the human brain would be valuable for the diagnosis of brain disorders and drug discovery. We provide an overview of current invasive and noninvasive techniques for measuring expression and functions of chromatin-modifying enzymes in the brain, emphasizing tools applicable to histone deacetylase (HDAC) enzymes as a leading example. The majority of current techniques are invasive and difficult to translate to what is happening within a human brain in vivo. However, recent progress in molecular imaging provides new, noninvasive ways to visualize epigenetics in the human brain. Neuroimaging tool development presents a unique set of challenges in order to identify and validate CNS radiotracers for HDACs and other histone-modifying enzymes. We summarize advances in the effort to image HDACs and HDAC inhibitory effects in the brain using positron emission tomography (PET) and highlight generalizable techniques that can be adapted to investigate other specific components of epigenetic machinery. Translational tools like neuroimaging by PET and magnetic resonance imaging provide the best way to link our current understanding of epigenetic changes with in vivo function in normal and diseased brains. These tools will be a critical addition to ex vivo methods to evaluate - and intervene - in CNS dysfunction. This article is part of a Special Issue entitled: Epigenetics in Brain Function. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Wang, C.; Schroeder, F. A.; Hooker, J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Schroeder, F. A.] Harvard Univ, Sch Med, Ctr Human Genet Res, Dept Psychiat,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hooker, JM (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Suite 2301, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu OI Hooker, Jacob/0000-0002-9394-7708 FU NCRR NIH HHS [S10 RR022976, S10 RR023385, S10 RR026666, S10 RR029495]; NIDA NIH HHS [R01 DA030321] NR 54 TC 8 Z9 8 U1 6 U2 16 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 APR 4 PY 2014 VL 264 BP 186 EP 197 DI 10.1016/j.neuroscience.2013.09.018 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AD2VK UT WOS:000333093700016 PM 24051365 ER PT J AU Vassoler, FM Sadri-Vakili, G AF Vassoler, F. M. Sadri-Vakili, G. TI MECHANISMS OF TRANSGENERATIONAL INHERITANCE OF ADDICTIVE-LIKE BEHAVIORS SO NEUROSCIENCE LA English DT Review DE transgenerational inheritance; epigenetics; cocaine; BDNF; prefrontal cortex ID PATERNAL FOLATE-DEFICIENCY; EPIGENETIC REGULATION; DNA METHYLATION; GENE-EXPRESSION; ENVIRONMENTAL SIGNALS; FAMILIAL TRANSMISSION; HISTONE ACETYLATION; SPERM EPIMUTATIONS; EMBRYO DEVELOPMENT; MATERNAL-BEHAVIOR AB Genetic factors are implicated in the heritability of drug abuse. However, even with advances in current technology no specific genes have been identified that are critical for the transmission of drug-induced phenotypes to subsequent generations. It is now evident that epigenetic factors contribute to disease heritability and represent a link between genes and the environment. Recently, epigenetic mechanisms have been shown to underlie drug-induced structural, synaptic, and behavioral plasticity by coordinating the expression of gene networks within the brain. Therefore, the epigenome provides a direct mechanism for drugs of abuse to influence the genetic events involved in the development of addiction as well as its heritability to subsequent generations. In this review we discuss the mechanisms underlying intergenerational epigenetic transmission, highlight studies that demonstrate this phenomenon with particular attention to the field of addiction, and identify gaps for future studies. This article is part of a Special Issue entitled: Epigenetics in Brain Function. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Vassoler, F. M.] Tufts Univ, Cummings Sch Vet Med, Dept Biomed Sci, Grafton, MA 01536 USA. [Sadri-Vakili, G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Sadri-Vakili, G (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Bldg 114,16th St,R2200, Charlestown, MA 02472 USA. EM gsadrivakili@partners.org OI Vassoler, Fair/0000-0001-5317-7174 FU NIDA NIH HHS [K02 DA018678, R01 DA033641] NR 91 TC 21 Z9 21 U1 7 U2 39 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 APR 4 PY 2014 VL 264 BP 198 EP 206 DI 10.1016/j.neuroscience.2013.07.064 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AD2VK UT WOS:000333093700017 PM 23920159 ER PT J AU Iinuma, R Ke, YG Jungmann, R Schlichthaerle, T Woehrstein, JB Yin, P AF Iinuma, Ryosuke Ke, Yonggang Jungmann, Ralf Schlichthaerle, Thomas Woehrstein, Johannes B. Yin, Peng TI Polyhedra Self-Assembled from DNA Tripods and Characterized with 3D DNA-PAINT SO SCIENCE LA English DT Article ID SINGLE-STRANDED-DNA; SUPERRESOLUTION MICROSCOPY; NANOSTRUCTURES; ORIGAMI; SHAPES; OCTAHEDRON; MOLECULE; BINDING; DESIGN AB DNA self-assembly has produced diverse synthetic three-dimensional polyhedra. These structures typically have a molecular weight no greater than 5 megadaltons. We report a simple, general strategy for one-step self-assembly of wireframe DNA polyhedra that are more massive than most previous structures. A stiff three-arm-junction DNA origami tile motif with precisely controlled angles and arm lengths was used for hierarchical assembly of polyhedra. We experimentally constructed a tetrahedron (20 megadaltons), a triangular prism (30 megadaltons), a cube (40 megadaltons), a pentagonal prism (50 megadaltons), and a hexagonal prism (60 megadaltons) with edge widths of 100 nanometers. The structures were visualized by means of transmission electron microscopy and three-dimensional DNA-PAINT super-resolution fluorescent microscopy of single molecules in solution. C1 [Iinuma, Ryosuke; Ke, Yonggang; Jungmann, Ralf; Schlichthaerle, Thomas; Woehrstein, Johannes B.; Yin, Peng] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Ke, Yonggang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ke, Yonggang] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Jungmann, Ralf; Woehrstein, Johannes B.; Yin, Peng] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Yin, P (reprint author), Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. EM py@hms.harvard.edu RI Jungmann, Ralf/A-6357-2015 OI Jungmann, Ralf/0000-0003-4607-3312 FU Office of Naval Research (ONR) [N000141110914]; ONR [N000141010827, N000141310593]; Army Research Office [W911NF1210238]; National Institutes of Health (NIH) [1DP2OD007292, 1R01EB018659, 5R21HD072481]; National Science Foundation (NSF) [CCF1054898, CCF1317291, CCF1162459, CMMI1333215]; JSR corporation; Wyss Institute for Biologically Inspired Engineering Faculty Startup Fund; Alexander von Humboldt Foundation FX We thank S. Woo and W. Shih for discussions. This work is supported by an Office of Naval Research (ONR) Young Investigator Program Award (N000141110914), ONR grants (N000141010827 and N000141310593), an Army Research Office grant (W911NF1210238), a National Institutes of Health (NIH) Director's New Innovator Award (1DP2OD007292), a NIH Transformative Research Award (1R01EB018659), a NIH grant (5R21HD072481), a National Science Foundation (NSF) Faculty Early Career Development Award (CCF1054898), a NSF Expedition in Computing Award (CCF1317291), NSF grants (CCF1162459, CMMI1333215), a gift from JSR corporation, and a Wyss Institute for Biologically Inspired Engineering Faculty Startup Fund to P.Y. R. I. acknowledges support from JSR corporation. R.J. acknowledges support from the Alexander von Humboldt Foundation through a Feodor-Lynen Fellowship. R. I., Y.K., and R.J. contributed equally. R. I. and Y.K. designed the system, conducted the experiments, analyzed the data, and wrote the paper. R.J. designed and performed the super-resolution study, analyzed the data, and wrote the paper. T. S. and J.B.W. performed the super-resolution experiments and analyzed the data. P.Y. conceived, designed, and supervised the study; interpreted the data; and wrote the paper. All authors commented on and approved the manuscript. NR 39 TC 72 Z9 74 U1 30 U2 198 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 4 PY 2014 VL 344 IS 6179 BP 65 EP 69 DI 10.1126/science.1250944 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE1RD UT WOS:000333746100052 PM 24625926 ER PT J AU Robertson, DJ Dominitz, JA AF Robertson, Douglas J. Dominitz, Jason A. TI Stool DNA and Colorectal-Cancer Screening SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID FECAL DNA C1 [Robertson, Douglas J.] White River Junct Vet Affairs VA Med Ctr, White River Jct, VT 05009 USA. [Robertson, Douglas J.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Robertson, DJ (reprint author), White River Junct Vet Affairs VA Med Ctr, White River Jct, VT 05009 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 14 TC 6 Z9 7 U1 0 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 3 PY 2014 VL 370 IS 14 BP 1350 EP 1351 DI 10.1056/NEJMe1400092 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE2VA UT WOS:000333830000015 PM 24645801 ER PT J AU Koch, R Demant, M Aung, T Diering, N Cicholas, A Chapuy, B Wenzel, D Lahmann, M Guntsch, A Kiecke, C Becker, S Hupfeld, T Venkataramani, V Ziepert, M Opitz, L Klapper, W Trumper, L Wulf, GG AF Koch, Raphael Demant, Martin Aung, Thiha Diering, Nina Cicholas, Anna Chapuy, Bjoern Wenzel, Dirk Lahmann, Marlen Guentsch, Annemarie Kiecke, Christina Becker, Sabrina Hupfeld, Timo Venkataramani, Vivek Ziepert, Marita Opitz, Lennart Klapper, Wolfram Truemper, Lorenz Wulf, Gerald G. TI Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; DRUG EFFLUX CAPACITY; BETA-CATENIN; SIDE POPULATION; ELDERLY-PATIENTS; TRANSPORTER A3; GROWTH-FACTORS; CANCER-CELLS; IN-VIVO AB Tumors are composed of phenotypically heterogeneous cell populations. The non-genomic mechanisms underlying transitions and interactions between cell populations are largely unknown. Here, we show that diffuse large B-cell lymphomas possess a self-organized infrastructure comprising side population (SP) and non-SP cells, where transitions between clonogenic states are modulated by exosome-mediated Wnt signaling. DNA methylation modulated SP-non-SP transitions and was correlated with the reciprocal expressions of Wnt signaling pathway agonist Wnt3a in SP cells and the antagonist secreted frizzled-related protein 4 in non-SP cells. Lymphoma SP cells exhibited autonomous clonogenicity and exported Wnt3a via exosomes to neighboring cells, thus modulating population equilibrium in the tumor. C1 [Koch, Raphael; Demant, Martin; Aung, Thiha; Diering, Nina; Cicholas, Anna; Lahmann, Marlen; Guentsch, Annemarie; Kiecke, Christina; Becker, Sabrina; Hupfeld, Timo; Venkataramani, Vivek; Truemper, Lorenz; Wulf, Gerald G.] Univ Gottingen, Dept Hematol & Oncol, D-37075 Gottingen, Germany. [Chapuy, Bjoern] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wenzel, Dirk] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. [Ziepert, Marita] Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Opitz, Lennart] Funct Genom Ctr Zurich, Zurich, Switzerland. [Klapper, Wolfram] Hematopathol Sect, Kiel, Germany. [Klapper, Wolfram] Lymph Node Registry, Kiel, Germany. RP Wulf, GG (reprint author), Univ Gottingen, Dept Hematol & Oncol, Robert Koch Str 40, D-37075 Gottingen, Germany. EM gwulf@med.uni-goettingen.de RI Klapper, Wolfram/S-6314-2016 FU Deutsche Forschungsgemeinschaft [DFG Wu 310/3-1]; University Medicine Goettingen FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG Wu 310/3-1) (G.G.W.) and by the University Medicine Goettingen (Jacob-Henle program grant) (T.A.) (Forschungsforderung) (R.K.). NR 49 TC 19 Z9 21 U1 3 U2 15 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 3 PY 2014 VL 123 IS 14 BP 2189 EP 2198 DI 10.1182/blood-2013-08-523886 PG 10 WC Hematology SC Hematology GA AH1OE UT WOS:000335889600015 PM 24563408 ER PT J AU Mayeur, C Lohmeyer, LK Leyton, P Kao, SM Pappas, AE Kolodziej, SA Spagnolli, E Yu, BL Galdos, RL Yu, PB Peterson, RT Bloch, DB Bloch, KD Steinbicker, AU AF Mayeur, Claire Lohmeyer, Lisa K. Leyton, Patricio Kao, Sonya M. Pappas, Alexandra E. Kolodziej, Starsha A. Spagnolli, Ester Yu, Binglan Galdos, Rita L. Yu, Paul B. Peterson, Randall T. Bloch, Donald B. Bloch, Kenneth D. Steinbicker, Andrea U. TI The type I BMP receptor Alk3 is required for the induction of hepatic hepcidin gene expression by interleukin-6 SO BLOOD LA English DT Article ID REGULATORY PEPTIDE HEPCIDIN; IRON-DEFICIENCY ANEMIA; CHRONIC INFLAMMATION; CHRONIC DISEASE; MICE; PROTEIN; METABOLISM; OVERLOAD; STAT3; CELLS AB Increased IL-6 production induces, via STAT3 phosphorylation, hepatic transcription of the gene encoding the iron-regulatory hormone, hepcidin, leading to development of anemia of chronic disease (ACD). Inhibition of bone morphogenetic protein (BMP) signaling prevents the induction of hepcidin gene expression by IL-6 and ameliorates ACD. Using mice with hepatocyte-specific deficiency of Alk2 or Alk3, we sought to identify the BMP type I receptor that participates in IL-6-mediated induction of hepcidin gene expression. Mice were injected with adenovirus specifying IL-6 (Ad.IL-6) or control adenovirus. Seventy-two hours later, serum iron concentrations and hepatic levels of STAT3 phosphorylation and hepcidin messenger RNA were measured. Additional mice were injected with recombinant murine IL-6 (mIL-6) or vehicle, and hepatic hepcidin gene expression was measured 4 hours later. Deficiency of Alk2 or Alk3 did not alter the ability of Ad.IL-6 injection to induce hepatic STAT3 phosphorylation. Ad.IL-6 increased hepatic hepcidin messenger RNA levels and decreased serum iron concentrations in Alk2-but not Alk3-deficient mice. Similarly, administration of mIL-6 induced hepatic hepcidin gene expression in Alk2- but not Alk3-deficient mice. These results demonstrate that the ability of IL-6 to induce hepatic hepcidin gene expression and reduce serum iron concentrations is dependent on the BMP type I receptor Alk3. C1 [Mayeur, Claire; Lohmeyer, Lisa K.; Leyton, Patricio; Kao, Sonya M.; Pappas, Alexandra E.; Kolodziej, Starsha A.; Spagnolli, Ester; Yu, Binglan; Bloch, Donald B.; Bloch, Kenneth D.; Steinbicker, Andrea U.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Galdos, Rita L.; Bloch, Donald B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Yu, Paul B.; Peterson, Randall T.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Yu, Paul B.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Steinbicker, Andrea U.] Univ Munster, Univ Hosp Muenster, Dept Anesthesiol Intens Care & Pain Med, D-48149 Munster, Germany. RP Steinbicker, AU (reprint author), Univ Hosp Muenster, Dept Anesthesiol Intens Care & Pain Med, Albert Schweitzer Campus 1,Gebaude A1, D-48149 Munster, Germany. EM andrea.steinbicker@ukmuenster.de OI Yu, Paul/0000-0003-2145-4944 FU Deutsche Forschungsgemeinschaft [DFG SW 119/3-1]; "Innovative Medical Research" of the University of Muenster Medical School [IMF-ST-111206]; Deanery of Muenster Medical School; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [R01DK082971]; Fondation LeDucq FX This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG SW 119/3-1), "Innovative Medical Research" of the University of Muenster Medical School (IMF-ST-111206) (A.U.S.), the Deanery of Muenster Medical School (A.U.S.), the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082971) (R.T.P. and K.D.B.), and a grant from the Fondation LeDucq (P.B.Y. and K.D.B.). NR 37 TC 14 Z9 15 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 3 PY 2014 VL 123 IS 14 BP 2261 EP 2268 DI 10.1182/blood-2013-02-480095 PG 8 WC Hematology SC Hematology GA AH1OE UT WOS:000335889600023 PM 24501215 ER PT J AU Lu, A Kabaleeswaran, V Fu, TM Magupalli, VG Wu, H AF Lu, Alvin Kabaleeswaran, Venkataraman Fu, Tianmin Magupalli, Venkat Giri Wu, Hao TI Crystal Structure of the F27G AIM2 PYD Mutant and Similarities of Its Self-Association to DED/DED Interactions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE AIM2; PYD; interaction; inflammasome; DED ID DEATH-EFFECTOR DOMAIN; PYRIN DOMAIN; CYTOPLASMIC DNA; NMR STRUCTURE; INFLAMMASOME; PROTEIN; ASC; ACTIVATION; INSIGHTS; RECEPTOR AB Absent in melanoma 2 (AIM2) is a cytoplasmic double-stranded DNA sensor involved in innate immunity. It uses its C-terminal HIN domain for recognizing double-stranded DNA and its N-terminal pyrin domain (PYD) for eliciting downstream effects through recruitment and activation of apoptosis-associated Speck-like protein containing CARD (ASC). ASC in turn recruits caspase-1 and/or caspase-11 to form the AIM2 inflammasome. The activated caspases process proinflammatory cytokines IL-beta and IL-18 and induce the inflammatory form of cell death pyroptosis. Here we show that AIM PYD (AIM2(PYD)) self-oligomerizes. We notice significant sequence homology of AIM2PYD with the hydrophobic patches of death effector domain (DED)-containing proteins and confirm that mutations on these residues disrupt AIM2PYD self-association. The crystal structure at 1.82 angstrom resolution of such a mutant, F27G of AIM2PYD, shows the canonical six-helix (H1-H6) bundle fold in the death domain superfamily. In contrast to the wild-type AIM2(PYD) structure crystallized in fusion with the large maltose-binding protein tag, the H2-H3 region of the AIM2(PYD) F27G is well defined with low B-factors. Structural analysis shows that the conserved hydrophobic patches engage in a type I interaction that has been observed in DED/DED and other death domain superfamily interactions. While previous mutagenesis studies of PYDs point to the involvement of charged interactions, our results reveal the importance of hydrophobic interactions in the same interfaces. These centrally localized hydrophobic residues within fairly charged patches may form the hot spots in AIM2(PYD) self-association and may represent a common mode of PYD/PYD interactions in general. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lu, Alvin; Kabaleeswaran, Venkataraman; Fu, Tianmin; Magupalli, Venkat Giri; Wu, Hao] Harvard Univ, Sch Med, Program Cellular & Mol Med, Dept Biol Chem & Mol Pharmacol,Boston Childrens H, Boston, MA 02115 USA. RP Wu, H (reprint author), Harvard Univ, Sch Med, Program Cellular & Mol Med, Dept Biol Chem & Mol Pharmacol,Boston Childrens H, Boston, MA 02115 USA. EM hao.wu@childrens.harvard.edu OI Lu, Alvin/0000-0003-2353-848X FU NIAID NIH HHS [R37 AI050872]; NIGMS NIH HHS [P41 GM111244] NR 38 TC 13 Z9 13 U1 1 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD APR 3 PY 2014 VL 426 IS 7 BP 1420 EP 1427 DI 10.1016/j.jmb.2013.12.029 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AF1MM UT WOS:000334478000007 PM 24406744 ER PT J AU Marino-Enriiquez, A Ou, WB Cowley, G Luo, B Jonker, AH Mayeda, M Okamoto, M Eilers, G Czaplinski, JT Sicinska, E Wang, Y Taguchi, T Demetri, GD Root, DE Fletcher, JA AF Marino-Enriquez, A. Ou, W-B Cowley, G. Luo, B. Jonker, A. H. Mayeda, M. Okamoto, M. Eilers, G. Czaplinski, J. T. Sicinska, E. Wang, Y. Taguchi, T. Demetri, G. D. Root, D. E. Fletcher, J. A. TI Genome-wide functional screening identifies CDC37 as a crucial HSP90-cofactor for KIT oncogenic expression in gastrointestinal stromal tumors SO ONCOGENE LA English DT Article DE CDC37; HSP90; GIST; targeted therapy; functional genomics; shRNA library ID IMATINIB MESYLATE; RESISTANCE; INHIBITOR; MUTATIONS; ACTIVATION; CANCER; TRIAL AB Most gastrointestinal stromal tumors (GISTs) contain KIT or PDGFRA kinase gain-of-function mutations, and therefore respond clinically to imatinib and other tyrosine kinase inhibitor (TKI) therapies. However, clinical progression subsequently results from selection of TKI-resistant clones, typically containing secondary mutations in the KIT kinase domain, which can be heterogeneous between and within GIST metastases in a given patient. TKI-resistant KIT oncoproteins require HSP90 chaperoning and are potently inactivated by HSP90 inhibitors, but clinical applications in GIST patients are constrained by the toxicity resulting from concomitant inactivation of various other HSP90 client proteins, beyond KIT and PDGFRA. To identify novel targets responsible for KIT oncoprotein function, we performed parallel genome-scale short hairpin RNA (shRNA)-mediated gene knockdowns in KIT-mutant GIST-T1 and GIST882. GIST cells were infected with a lentiviral shRNA pooled library targeting 11 194 human genes, and allowed to proliferate for 5-7 weeks, at which point assessment of relative hairpin abundance identified the HSP90 cofactor, CDC37, as one of the top six GIST-specific essential genes. Validations in treatment-naive (GIST-T1, GIST882) vs imatinib-resistant GISTs (GIST48, GIST430) demonstrated that: (1) CDC37 interacts with oncogenic KIT; (2) CDC37 regulates expression and activation of KIT and downstream signaling intermediates in GIST; and (3) unlike direct HSP90 inhibition, CDC37 knockdown accomplishes prolonged KIT inhibition (420 days) in GIST. These studies highlight CDC37 as a key biologic vulnerability in both imatinib-sensitive and imatinib-resistant GIST. CDC37 targeting is expected to be selective for KIT/PDGFRA and a subset of other HSP90 clients, and thereby represents a promising strategy for inactivating the myriad KIT/PDGFRA oncoproteins in TKI-resistant GIST patients. C1 [Marino-Enriquez, A.; Ou, W-B; Jonker, A. H.; Mayeda, M.; Eilers, G.; Wang, Y.; Fletcher, J. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Marino-Enriquez, A.] Univ Autonoma Madrid, Hosp Univ La Paz, Fdn Invest Biomed FIBHULP, IdiPAZ,Dept Anat Patol, Madrid, Spain. [Ou, W-B] Tsinghua Univ, Yangtze Delta Reg Inst, Zhejiang Prov Key Lab Appl Enzymol, Jiaxing, Zhejiang, Peoples R China. [Cowley, G.; Luo, B.; Okamoto, M.; Root, D. E.] Harvard & MIT, Broad Inst, RNAi Platform, Cambridge, MA USA. [Czaplinski, J. T.; Sicinska, E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol Med Oncol, Boston, MA 02115 USA. [Taguchi, T.] Kochi Univ, Grad Sch Kuroshio Sci, Dept Human Hlth & Med Sci, Nankoku, Kochi, Japan. [Demetri, G. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Marino-Enriiquez, A (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM admarino@partners.org; jfletcher@partners.org FU GI SPORE [1P50CA12703-05]; Virginia and Daniel K Ludwig Trust for Cancer Research; Paul's Posse and Team Cesarini of the Pan Mass Challenge; LifeRaft Group; GIST Cancer Research Fund; Sarcoma Alliance for Research Through Collaboration (SARC) Career Development Award; Qianjiang Talents Project of Zhejiang [2012R10079]; Science and Technology Bureau of Jiaxing, Zhejiang [2012AY1039]; Major Science and Technology Special Project of Zhejiang Province [2012C03007-4]; RNAI Consortium (TRC) FX Adrian Marino-Enriquez, Wen-Bin Ou, Yuexiang Wang, Jonathan A Fletcher and George D Demetri, are supported by the GI SPORE 1P50CA12703-05, Virginia and Daniel K Ludwig Trust for Cancer Research, Paul's Posse and Team Cesarini of the Pan Mass Challenge, LifeRaft Group and the GIST Cancer Research Fund. Adrian Marino-Enriquez is also supported by a Sarcoma Alliance for Research Through Collaboration (SARC) Career Development Award. Wen-Bin Ou is also supported by Qianjiang Talents Project of Zhejiang (2012R10079), a grant from the Science and Technology Bureau of Jiaxing, Zhejiang (2012AY1039) and the Major Science and Technology Special Project of Zhejiang Province (2012C03007-4). The RNAI Consortium (TRC) supported the development of pooled screening methods used for these screens. NR 23 TC 11 Z9 11 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD APR 3 PY 2014 VL 33 IS 14 BP 1872 EP 1876 DI 10.1038/onc.2013.127 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AE9RE UT WOS:000334345500013 PM 23584476 ER PT J AU Giacobbi, PR Buman, MP Dzierzewski, JM Aiken-Morgan, AT Roberts, BL Marsiske, M Knutson, N McCrae, CS AF Giacobbi, Peter R., Jr. Buman, Matthew P. Dzierzewski, Joseph M. Aiken-Morgan, Adrienne T. Roberts, Beverly L. Marsiske, Michael Knutson, Nicholas McCrae, Christina S. TI Content and Perceived Utility of Mental Imagery by Older Adults in a Peer-Delivered Physical Activity Intervention SO JOURNAL OF APPLIED SPORT PSYCHOLOGY LA English DT Article ID EXERCISE IMAGERY; COMPLEMENTARY; MEDICINE; PROGRAM AB Imagery interventions intended to increase exercise behavior are rare. The Active Adult Mentoring Program (AAMP) was a randomized controlled trial with imagery content. The purposes of this study were to examine the content and perceived utility of mental imagery with 24 AAMP participants (M-age = 65.00, SD = 8.79years). Digital recordings of AAMP sessions and post-intervention interviews were content-analyzed. Emergent themes included images of the physical activity context and negative impressions about imagery. Post-intervention interviews revealed that 13 participants reported positive experiences using mental imagery while 9 would not engage in further use. Important implications are discussed. C1 [Giacobbi, Peter R., Jr.] W Virginia Univ, Morgantown, WV 26506 USA. [Buman, Matthew P.] Arizona State Univ, Tempe, AZ 85287 USA. [Dzierzewski, Joseph M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dzierzewski, Joseph M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Aiken-Morgan, Adrienne T.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Roberts, Beverly L.; Marsiske, Michael; McCrae, Christina S.] Univ Florida, Gainesville, FL 32611 USA. [Knutson, Nicholas] Univ Arizona, Tucson, AZ 85721 USA. RP Giacobbi, PR (reprint author), W Virginia Univ, Morgantown, WV 26506 USA. EM peter.giacobbi@mail.wvu.edu OI Marsiske, Michael/0000-0001-5973-2116; McCrae, Christina/0000-0003-4313-6867 FU National Institute on Aging [1R36AG029664-01, F31-AG-032802, T32-AG000029]; University of Florida (Age Network research award); Research Opportunity Fund in the College of Health and Human Performance at the University of Florida; Department of Veterans Affairs Advanced Geriatrics Fellowship Program, an Institutional Training Grant [T32-AG-020499]; Public Health Service Training Grant from the National Heart, Lung, and Blood Institute [5-T32-HL-007034] FX This work was supported by the National Institute on Aging (1R36AG029664-01, PI: Aiken-Morgan) and University of Florida (Age Network research award, PI: McCrae). This work was also supported, in part, by a Research Opportunity Fund in the College of Health and Human Performance at the University of Florida. Joseph M. Dzierzewski was supported by the Department of Veterans Affairs Advanced Geriatrics Fellowship Program, an Institutional Training Grant, T32-AG-020499, awarded to the University of Florida by the National Institute on Aging, and an Individual Training Grant, F31-AG-032802, awarded by the National Institute on Aging. Matthew P. Buman was supported by Public Health Service Training Grant, 5-T32-HL-007034, from the National Heart, Lung, and Blood Institute. Adrienne T. Aiken-Morgan was supported by an Institutional Training Grant, T32-AG000029, to Duke University by the National Institute on Aging. None of the authors have declared a conflict of interest. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources, nor were funding sources responsible for the design, methods, subject recruitment, data collection, analysis or preparation of paper. NR 25 TC 2 Z9 2 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1041-3200 EI 1533-1571 J9 J APPL SPORT PSYCHOL JI J. Appl. Sport Psychol. PD APR 3 PY 2014 VL 26 IS 2 BP 129 EP 143 DI 10.1080/10413200.2013.803502 PG 15 WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology; Sport Sciences SC Social Sciences - Other Topics; Psychology; Sport Sciences GA AE4WD UT WOS:000333986100001 PM 25067894 ER PT J AU Maynard, MA Marino-Enriquez, A Fletcher, JA Dorfman, DM Raut, CP Yassa, L Guo, CC Wang, YX Dorfman, C Feldman, HA Frates, MC Song, HD Jugo, RH Taguchi, T Hershman, JM Larsen, PR Huang, SA AF Maynard, Michelle A. Marino-Enriquez, Adrian Fletcher, Jonathan A. Dorfman, David M. Raut, Chandrajit P. Yassa, Leila Guo, Cuicui Wang, Yuexiang Dorfman, Clara Feldman, Henry A. Frates, Mary C. Song, Huaidong Jugo, Rebecca H. Taguchi, Takahiro Hershman, Jerome M. Larsen, P. Reed Huang, Stephen A. TI Thyroid Hormone Inactivation in Gastrointestinal Stromal Tumors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYPE-3 IODOTHYRONINE DEIODINASE; CONSUMPTIVE HYPOTHYROIDISM; SUNITINIB; MUTATIONS; SERUM; KIT AB Gastrointestinal stromal tumors (GISTs) are resistant to traditional chemotherapy but are responsive to the tyrosine kinase inhibitors imatinib and sunitinib.(1) The use of these agents has improved the outcome for patients but is associated with adverse effects, including hypothyroidism.(2) Multiple mechanisms of this effect have been proposed, including decreased iodine organification(3) and glandular capillary regression.(4) Here we report the finding of consumptive hypothyroidism caused by marked overexpression of the thyroid hormone-inactivating enzyme type 3 iodothyronine deiodinase (D3) within the tumor. Affected patients warrant increased monitoring and may require supernormal thyroid hormone supplementation. C1 [Maynard, Michelle A.; Guo, Cuicui; Dorfman, Clara; Song, Huaidong; Jugo, Rebecca H.; Huang, Stephen A.] Boston Childrens Hosp, Div Endocrinol, Thyroid Program, Boston, MA 02115 USA. [Feldman, Henry A.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Marino-Enriquez, Adrian; Fletcher, Jonathan A.; Dorfman, David M.; Wang, Yuexiang] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Frates, Mary C.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Yassa, Leila; Larsen, P. Reed; Huang, Stephen A.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Thyroid Sect, Boston, MA 02115 USA. [Fletcher, Jonathan A.; Raut, Chandrajit P.; Larsen, P. Reed; Huang, Stephen A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Taguchi, Takahiro] Kochi Med Sch, Dept Neurobiol & Anat, Nankoku, Kochi, Japan. [Hershman, Jerome M.] Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA USA. RP Huang, SA (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM stephen.huang@childrens.harvard.edu FU National Institutes of Health [DK076099, DK044128, 1P50CA12703]; William F. Milton Foundation Award; Harvard Clinical and Translational Science Center [NIH UL1 RR-025758, NIH UL1 TR-001102] FX Supported by a donation from the Murray Family, grants from the National Institutes of Health (DK076099, DK044128, and 1P50CA12703), the William F. Milton Foundation Award, and a grant from the Harvard Clinical and Translational Science Center (NIH UL1 RR-025758 and NIH UL1 TR-001102, to Dr. Feldman). NR 25 TC 12 Z9 13 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 3 PY 2014 VL 370 IS 14 BP 1327 EP 1334 DI 10.1056/NEJMoa1308893 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AE2VA UT WOS:000333830000011 PM 24693892 ER PT J AU Liu, Y Li, X Aryee, MJ Ekstrom, TJ Padyukov, L Klareskog, L Vandiver, A Moore, AZ Tanaka, T Ferrucci, L Fallin, MD Feinberg, AP AF Liu, Yun Li, Xin Aryee, Martin J. Ekstrom, Tomas J. Padyukov, Leonid Klareskog, Lars Vandiver, Amy Moore, Ann Zenobia Tanaka, Toshiko Ferrucci, Luigi Fallin, M. Daniele Feinberg, Andrew P. TI GeMes, Clusters of DNA Methylation under Genetic Control, Can Inform Genetic and Epigenetic Analysis of Disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID EPIGENOME-WIDE ASSOCIATION; HUMAN GENOME; LOCI; EPIDEMIOLOGY; POPULATION; CONSORTIUM; PATTERNS; SMOKING; CELL AB Epigenetic marks such as DNA methylation have generated great interest in the study of human disease. However, studies of DNA methylation have not established population-epigenetics principles to guide design, efficient statistics, or interpretation. Here, we show that the clustering of correlated DNA methylation at CpGs was similar to that of linkage-disequilibrium (LD) correlation in genetic SNP variation but for much shorter distances. Some clustering of methylated CpGs appeared to be genetically driven. Further, a set of correlated methylated CpGs related to a single SNP-based LD block was not always physically contiguous-segments of uncorrelated methylation as long as 300 kb could be interspersed in the cluster. Thus, we denoted these sets of correlated CpGs as GeMes, defined as potentially noncontiguous methylation clusters under the control of one or more methylation quantitative trait loci. This type of correlated methylation structure has implications for both biological functions of DNA methylation and for the design, analysis, and interpretation of epigenome-wide association studies. C1 [Liu, Yun; Li, Xin; Aryee, Martin J.; Vandiver, Amy; Fallin, M. Daniele; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Liu, Yun; Li, Xin; Vandiver, Amy; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Aryee, Martin J.] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02114 USA. [Aryee, Martin J.] Harvard Univ, Sch Med, Charlestown, MA 02114 USA. [Ekstrom, Tomas J.; Padyukov, Leonid; Klareskog, Lars] Karolinska Inst, Ctr Mol Med, S-17176 Stockholm, Sweden. [Ekstrom, Tomas J.; Padyukov, Leonid; Klareskog, Lars] Univ Hosp, S-17176 Stockholm, Sweden. [Ekstrom, Tomas J.] Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden. [Padyukov, Leonid; Klareskog, Lars] Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden. [Moore, Ann Zenobia; Tanaka, Toshiko; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Fallin, M. Daniele] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Deparment Mental Hlth, Baltimore, MD 21205 USA. RP Fallin, MD (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. EM dfallin@jhsph.edu; afeinberg@jhu.edu OI Klareskog, Lars/0000-0001-9601-6186; Padyukov, Leonid/0000-0003-2950-5670 FU National Institutes of Health (NIH) [HG003233, AG042187]; Swedish AFA Insurance grants; Swedish Strategic Research Foundation; European Research Council; Intramural Research Program of the NIH National Institute on Aging; MedStar Research Institute FX We thank Rafael Irizarry for the idea of using 450K array replicates to estimate and describe between-CpG correlations across the genome. This work was supported by National Institutes of Health (NIH) grants HG003233 (A.P.F) and AG042187 (to A.P.F. and M.D.F.), by Swedish AFA Insurance grants to T.J.E., and by grants to L.K. from the Swedish Strategic Research Foundation and European Research Council. The Baltimore Longitudinal Study of Aging was supported in part by the Intramural Research Program of the NIH National Institute on Aging. A portion of that support was through a research-and-development contract with MedStar Research Institute. NR 44 TC 38 Z9 38 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 3 PY 2014 VL 94 IS 4 BP 485 EP 495 DI 10.1016/j.ajhg.2014.02.011 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AE1XC UT WOS:000333765300001 PM 24656863 ER PT J AU Woo, D Falcone, GJ Devan, WJ Brown, WM Biffi, A Howard, TD Anderson, CD Brouwers, HB Valant, V Battey, TWK Radmanesh, F Raffeld, MR Baedorf-Kassis, S Deka, R Woo, JG Martin, LJ Haverbusch, M Moomaw, CJ Sun, GY Broderick, JP Flaherty, ML Martini, SR Kleindorfer, DO Kissela, B Comeau, ME Jagiella, JM Schmidt, H Freudenberger, P Pichler, A Enzinger, C Hansen, BM Norrving, B Jimenez-Conde, J Giralt-Steinhauer, E Elosua, R Cuadrado-Godia, E Soriano, C Roquer, J Kraft, P Ayres, AM Schwab, K McCauley, JL Pera, J Urbanik, A Rost, NS Goldstein, JN Viswanathan, A Stogerer, EM Tirschwell, DL Selim, M Brown, DL Silliman, SL Worrall, BB Meschia, JF Kidwell, CS Montaner, J Fernandez-Cadenas, I Delgado, P Malik, R Dichgans, M Greenberg, SM Rothwell, PM Lindgren, A Slowik, A Schmidt, R Langefeld, CD Rosand, J AF Woo, Daniel Falcone, Guido J. Devan, William J. Brown, W. Mark Biffi, Alessandro Howard, Timothy D. Anderson, Christopher D. Brouwers, H. Bart Valant, Valerie Battey, Thomas W. K. Radmanesh, Farid Raffeld, Miriam R. Baedorf-Kassis, Sylvia Deka, Ranjan Woo, Jessica G. Martin, Lisa J. Haverbusch, Mary Moomaw, Charles J. Sun, Guangyun Broderick, Joseph P. Flaherty, Matthew L. Martini, Sharyl R. Kleindorfer, Dawn O. Kissela, Brett Comeau, Mary E. Jagiella, Jeremiasz M. Schmidt, Helena Freudenberger, Paul Pichler, Alexander Enzinger, Christian Hansen, Bjorn M. Norrving, Bo Jimenez-Conde, Jordi Giralt-Steinhauer, Eva Elosua, Roberto Cuadrado-Godia, Elisa Soriano, Carolina Roquer, Jaume Kraft, Peter Ayres, Alison M. Schwab, Kristin McCauley, Jacob L. Pera, Joanna Urbanik, Andrzej Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Stoegerer, Eva-Maria Tirschwell, David L. Selim, Magdy Brown, Devin L. Silliman, Scott L. Worrall, Bradford B. Meschia, James F. Kidwell, Chelsea S. Montaner, Joan Fernandez-Cadenas, Israel Delgado, Pilar Malik, Rainer Dichgans, Martin Greenberg, Steven M. Rothwell, Peter M. Lindgren, Arne Slowik, Agnieszka Schmidt, Reinhold Langefeld, Carl D. Rosand, Jonathan CA Int Stroke Genetics Consortium TI Meta-analysis of Genome-wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BRAIN-BARRIER BREAKDOWN; POLYAMINE-SITE; RISK-FACTORS; STROKE; POPULATION; BURDEN; VOLUME; GENE; TRANSCRIPTION; MECHANISMS AB Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 x 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 x 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p 1.6 x 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 x 10(-4); meta-analysis p = 2.2 x 10(-10)) but not for 12q21.1 (p = 0.55; metaanalysis p = 2.6 x 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly. C1 [Woo, Daniel; Haverbusch, Mary; Moomaw, Charles J.; Broderick, Joseph P.; Flaherty, Matthew L.; Martini, Sharyl R.; Kleindorfer, Dawn O.; Kissela, Brett] Univ Cincinnati, Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH 45267 USA. [Falcone, Guido J.; Devan, William J.; Biffi, Alessandro; Anderson, Christopher D.; Brouwers, H. Bart; Valant, Valerie; Battey, Thomas W. K.; Radmanesh, Farid; Raffeld, Miriam R.; Baedorf-Kassis, Sylvia; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Woo, Daniel; Falcone, Guido J.; Devan, William J.; Biffi, Alessandro; Anderson, Christopher D.; Brouwers, H. Bart; Valant, Valerie; Battey, Thomas W. K.; Radmanesh, Farid; Raffeld, Miriam R.; Baedorf-Kassis, Sylvia; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. [Woo, Daniel; Falcone, Guido J.; Devan, William J.; Biffi, Alessandro; Anderson, Christopher D.; Brouwers, H. Bart; Valant, Valerie; Battey, Thomas W. K.; Radmanesh, Farid; Raffeld, Miriam R.; Baedorf-Kassis, Sylvia; Ayres, Alison M.; Schwab, Kristin; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Falcone, Guido J.; Devan, William J.; Biffi, Alessandro; Anderson, Christopher D.; Brouwers, H. Bart; Valant, Valerie; Battey, Thomas W. K.; Radmanesh, Farid; Raffeld, Miriam R.; Baedorf-Kassis, Sylvia; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02141 USA. [Falcone, Guido J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Brown, W. Mark; Howard, Timothy D.; Comeau, Mary E.; Langefeld, Carl D.] Wake Forest Univ, Ctr Publ Hlth Genom, Winston Salem, NC 27157 USA. [Brown, W. Mark; Howard, Timothy D.; Comeau, Mary E.; Langefeld, Carl D.] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Deka, Ranjan; Sun, Guangyun] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Woo, Jessica G.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Martin, Lisa J.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Jagiella, Jeremiasz M.; Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, Coll Med, PL-31008 Krakow, Poland. [Schmidt, Helena; Freudenberger, Paul] Med Univ Graz, Inst Mol Biol & Med Biochem, A-8010 Graz, Austria. [Pichler, Alexander; Enzinger, Christian; Stoegerer, Eva-Maria; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, A-8036 Graz, Austria. [Enzinger, Christian] Med Univ Graz, Div Neuroradiol, Dept Radiol, A-8036 Graz, Austria. [Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Lund Univ, Dept Clin Sci Lund, S-22185 Lund, Sweden. [Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Skane Univ Hosp, Dept Neurol, S-22185 Lund, Sweden. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; Roquer, Jaume] Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Dept Neurol, DCEXS UPF,Neurovasc Res Unit, Barcelona 08035, Spain. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; Roquer, Jaume] Inst Hosp del Mar Invest Med, Cardiovasc Epidemiol & Genet Res Grp, Barcelona 08003, Spain. [McCauley, Jacob L.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Urbanik, Andrzej] Jagiellonian Univ, Coll Med, Dept Radiol, PL-31008 Krakow, Poland. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Tirschwell, David L.] Univ Washington, Stroke Ctr, Harborview Med Ctr, Seattle, WA 98104 USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Stroke Div, Dept Neurol, Boston, MA 02215 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI 48109 USA. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL 32209 USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA 22908 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Kidwell, Chelsea S.] Univ Arizona, Dept Neurol, Tucson, AZ 85724 USA. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, Barcelona 08035, Spain. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, Barcelona 08035, Spain. [Fernandez-Cadenas, Israel] Fundacio Docencia & Recerca Mutuaterrassa, Barcelona 08010, Spain. [Malik, Rainer; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, D-80539 Munich, Germany. [Malik, Rainer; Dichgans, Martin] Munich Cluster Syst Neurol Synergy, D-80539 Munich, Germany. [Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford OX3 9DU, England. RP Woo, D (reprint author), Univ Cincinnati, Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH 45267 USA. EM daniel.woo@uc.edu; jrosand@partners.org RI JIMENEZ-CONDE, JORDI/C-1941-2012; Montaner, Joan/D-3063-2015; Martin, Lisa/E-2425-2016; Goldstein, Joshua/H-8953-2016; IBIS, NEUROVASCULAR/O-1855-2015; Falcone, Guido/L-2287-2016; OI Martin, Lisa/0000-0001-8702-9946; Falcone, Guido/0000-0002-6407-0302; Hansen, Bjorn/0000-0001-8661-9063; Brown, Devin/0000-0002-9815-3421; ELOSUA, ROBERTO/0000-0001-8235-0095; Norrving, Bo/0000-0002-8024-5096; Anderson, Christopher/0000-0002-0053-2002; Kissela, Brett/0000-0002-9773-4013 FU GERFHS, NIH [NS36695, NS30678]; GOCHA, NIH [R01NS059727]; Keane Stroke Genetics Research Fund; Edward and Maybeth Sonn Research Fund; University of Michigan General Clinical Research Center [M01 RR000042]; ERICH, NIH [NS069763]; HM-ICH, Instituto de Salud Carlos III [PI051737]; Fondos de Investigacion Sanitaria ISC III [PI10/02064]; Fondos FEDER/EDRF Red de Investigacion Cardiovascular [RD12/0042]; JUHSS, Polish Ministry of Education [N402 083934]; LSR, Lund University, Region Skane; Swedish Research Council [K2010-61X-20378-04-3]; Swedish Stroke Association; Freemasons Lodge of Instruction EOS in Lund; King Gustaf V foundation; Queen Victoria's foundation; NIH SPOTRIAS fellowship [P50NS061343]; American Brain Foundation; NIH [5K23NS059774, U01 NS074425, R01 NS062675, R01 HL098065, R01 NS070941, R18 HS017690]; NIHR; Wellcome Trust; Blue Cross Blue Shield of Michigan Foundation; Michigan Department of Community Health; University of Michigan FX We thank the Biorepository and Center for Genome Technology (University of Miami) (specifically Sandra West, Ioanna Konidari, and Susan Slifer) and Miguel Hernan for providing expert advice. Computing support, in part, provided by the Wake Forest Center for Public Health Genomics. Funding entities had no direct involvement in study design; data collection, analysis, and interpretation; writing of the manuscript; or the decision to submit for publication. Funding provided as follows: GERFHS, NIH grants NS36695 and NS30678; GOCHA, NIH grant R01NS059727, the Keane Stroke Genetics Research Fund, the Edward and Maybeth Sonn Research Fund, and the University of Michigan General Clinical Research Center M01 RR000042; ERICH, NIH grant NS069763; HM-ICH, Instituto de Salud Carlos III with the grants "Registro BASICMAR" Funding for Research in Health (PI051737), "GWALA project" from Fondos de Investigacion Sanitaria ISC III (PI10/02064), and Fondos FEDER/EDRF Red de Investigacion Cardiovascular (RD12/0042); JUHSS, Polish Ministry of Education grant N402 083934; LSR, Lund University, Region Skane, the Swedish Research Council (K2010-61X-20378-04-3), the Swedish Stroke Association, the Freemasons Lodge of Instruction EOS in Lund, and the King Gustaf V and Queen Victoria's foundations; G.J.F. and H.B.B., NIH SPOTRIAS fellowship P50NS061343; C.D.D., fellowship from the American Brain Foundation; J.N.G., NIH grant 5K23NS059774; P.M.R., awards from the NIHR and the Wellcome Trust; M.S., NIH grant U01 NS074425; and D.L.B., NIH grants R01 NS062675, R01 HL098065, R01 NS070941, and R18 HS017690, the Blue Cross Blue Shield of Michigan Foundation, Michigan Department of Community Health, and the University of Michigan. NR 34 TC 25 Z9 26 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 3 PY 2014 VL 94 IS 4 BP 511 EP 521 DI 10.1016/j.ajhg.2014.02.012 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AE1XC UT WOS:000333765300003 PM 24656865 ER PT J AU Zhang, XC Ling, JQ Barcia, G Jing, LL Wu, J Barry, BJ Mochida, GH Hill, RS Weimer, JM Stein, Q Poduri, A Partlow, JN Ville, D Dulac, O Yu, TW Lam, ATN Servattalab, S Rodriguez, J Boddaert, N Munnich, A Colleaux, L Zon, LI Soll, D Walsh, CA Nabbout, R AF Zhang, Xiaochang Ling, Jiqiang Barcia, Giulia Jing, Lili Wu, Jiang Barry, Brenda J. Mochida, Ganeshwaran H. Hill, R. Sean Weimer, Jill M. Stein, Quinn Poduri, Annapurna Partlow, Jennifer N. Ville, Dorothee Dulac, Olivier Yu, Tim W. Lam, Anh-Thu N. Servattalab, Sarah Rodriguez, Jacqueline Boddaert, Nathalie Munnich, Arnold Colleaux, Laurence Zon, Leonard I. Soell, Dieter Walsh, Christopher A. Nabbout, Rima TI Mutations in QARS, Encoding Glutaminyl-tRNA Synthetase, Cause Progressive Microcephaly, Cerebral-Cerebellar Atrophy, and Intractable Seizures SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MARIE-TOOTH-DISEASE; PONTOCEREBELLAR HYPOPLASIA; MAJOR DETERMINANT; PERRAULT SYNDROME; HEARING-LOSS; COMPLEX; PROTEIN; CLASSIFICATION; ORGANIZATION; DISSECTION AB Progressive microcephaly is a heterogeneous condition with causes including mutations in genes encoding regulators of neuronal survival. Here, we report the identification of mutations in QARS (encoding glutaminyl-tRNA synthetase [QARS]) as the causative variants in two unrelated families affected by progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres. Whole-exome sequencing of individuals from each family independently identified compound-heterozygous mutations in QARS as the only candidate causative variants. QARS was highly expressed in the developing fetal human cerebral cortex in many cell types. The four QARS mutations altered highly conserved amino acids, and the aminoacylation activity of QARS was significantly impaired in mutant cell lines. Variants p. Gly45Val and p.Tyr57His were located in the N-terminal domain required for QARS interaction with proteins in the multisynthetase complex and potentially with glutamine tRNA, and recombinant QARS proteins bearing either substitution showed an over 10-fold reduction in aminoacylation activity. Conversely, variants p.Arg403Trp and p.Arg515Trp, each occurring in a different family, were located in the catalytic core and completely disrupted QARS aminoacylation activity in vitro. Furthermore, p.Arg403Trp and p.Arg515Trp rendered QARS less soluble, and p.Arg403Trp disrupted QARS-RARS (arginyl-tRNA synthetase 1) interaction. In zebrafish, homozygous qars loss of function caused decreased brain and eye size and extensive cell death in the brain. Our results highlight the importance of QARS during brain development and that epilepsy due to impairment of QARS activity is unusually severe in comparison to other aminoacyl-tRNA synthetase disorders. C1 [Zhang, Xiaochang; Barry, Brenda J.; Mochida, Ganeshwaran H.; Hill, R. Sean; Partlow, Jennifer N.; Yu, Tim W.; Lam, Anh-Thu N.; Servattalab, Sarah; Rodriguez, Jacqueline; Walsh, Christopher A.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. [Zhang, Xiaochang; Barry, Brenda J.; Mochida, Ganeshwaran H.; Hill, R. Sean; Partlow, Jennifer N.; Yu, Tim W.; Lam, Anh-Thu N.; Servattalab, Sarah; Rodriguez, Jacqueline; Walsh, Christopher A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Zhang, Xiaochang; Jing, Lili; Barry, Brenda J.; Hill, R. Sean; Partlow, Jennifer N.; Lam, Anh-Thu N.; Servattalab, Sarah; Rodriguez, Jacqueline; Zon, Leonard I.; Walsh, Christopher A.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ling, Jiqiang; Soell, Dieter] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Ling, Jiqiang; Wu, Jiang] Univ Texas Hlth Sci Ctr Houston, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. [Barcia, Giulia; Dulac, Olivier; Nabbout, Rima] Hop Necker Enfants Malad, Assistance Publ Hop Paris, Ctr Reference Epilepsies Rares, Dept Pediat Neurol, F-75015 Paris, France. [Barcia, Giulia; Dulac, Olivier; Nabbout, Rima] Univ Paris 05, INSERM, U1129, F-75006 Paris, France. [Barcia, Giulia; Dulac, Olivier; Nabbout, Rima] Commissariat Energie Atom & Energies Alternat, INSERM, U1129, F-91191 Gif Sur Yvette, France. [Jing, Lili; Zon, Leonard I.] Harvard Univ, Sch Med, Boston Childrens Hosp, Harvard Stem Cell Inst,Stem Cell Program, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. [Weimer, Jill M.] Sanford Res, Sanford Childrens Hlth Res Ctr, Sioux Falls, SD 57104 USA. [Stein, Quinn] Sanford Sch Med, Dept Pediat, Sioux Falls, SD 57105 USA. [Stein, Quinn] Sanford Sch Med, Dept Ob Gyn, Sioux Falls, SD 57105 USA. [Poduri, Annapurna; Yu, Tim W.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Poduri, Annapurna; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Ville, Dorothee] Ctr Hosp Univ Lyon, Dept Pediat Neurol, F-69007 Lyon, France. [Boddaert, Nathalie] Univ Paris 05, Hop Necker Enfants Malades, Imagine Inst, INSERM,U781,Dept Pediat Radiol, F-75006 Paris, France. [Munnich, Arnold; Colleaux, Laurence] Univ Paris 05, Hop Necker Enfants Malades, Imagine Inst, INSERM,U781,Dept Genet, F-75006 Paris, France. [Walsh, Christopher A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Walsh, CA (reprint author), Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu; rima.nabbout@nck.aphp.fr RI zhang, xiaochang/G-4857-2014; Wu, Jiang/N-3838-2014; OI zhang, xiaochang/0000-0001-5768-7470; Wu, Jiang/0000-0002-9336-457X; Stein, Quinn/0000-0002-7670-9281; Ling, Jiqiang/0000-0003-4466-8304; Yu, Timothy/0000-0003-2988-7701 FU National Institute of Neurological Disorders and Stroke [R01 NS35129, K23 NS069784]; Manton Center for Orphan Disease Research; Foundation Maladies Rares; F. Hoffmann-La Roche Ltd. FX We would like to thank Nancy Mendelsohn and Janice Baker at Children's Hospitals and Clinics of Minnesota for organizing clinical visits and information; Wen Fan Hu and Divya Jayaraman for editing the paper; and Aldo Rozzo, Byoung-Il Bae, Xuyu Cai, all C.A.W. lab members, and Chris Cho (Yale University) for helpful discussions and technical assistance. Human tissue was obtained from the National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore. This project was supported by grants from the National Institute of Neurological Disorders and Stroke (R01 NS35129 to C.A.W. and K23 NS069784 to A. P.), the Manton Center for Orphan Disease Research (to C. A. W.), and Foundation Maladies Rares (to R.N.). G.H.M. is the recipient of a research grant from F. Hoffmann-La Roche Ltd. L.I.Z. is a founder and stockholder of Fate Therapeutics Inc. and Scholar Rock. C.A.W. is a Distinguished Investigator of the Paul G. Allen Foundation and a Howard Hughes Medical Institute Investigator. NR 41 TC 25 Z9 29 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 3 PY 2014 VL 94 IS 4 BP 547 EP 558 DI 10.1016/j.ajhg.2014.03.003 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AE1XC UT WOS:000333765300006 PM 24656866 ER PT J AU Gale, JT Shields, DC Ishizawa, Y Eskandar, EN AF Gale, John T. Shields, Donald C. Ishizawa, Yumiko Eskandar, Emad N. TI Reward and reinforcement activity in the nucleus accumbens during learning SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE nucleus accumbens; learning; reward; incentive salience; operant conditioning ID PAVLOVIAN APPROACH BEHAVIOR; VENTRAL STRIATUM; EFFERENT PROJECTIONS; BASAL GANGLIA; INCENTIVE SALIENCE; PREFRONTAL CORTEX; NEURONAL-ACTIVITY; DOPAMINE FUNCTION; MONETARY REWARD; RHESUS-MONKEY AB The nucleus accumbens core (NAcc) has been implicated in learning associations between sensory cues and profitable motor responses. However, the precise mechanisms that underlie these functions remain unclear. We recorded single-neuron activity from the NAcc of primates trained to perform a visual-motor associative learning task. During learning, we found two distinct classes of NAcc neurons. The first class demonstrated progressive increases in firing rates at the go-cue, feedback/tone and reward epochs of the task, as novel associations were learned. This suggests that these neurons may play a role in the exploitation of rewarding behaviors. In contrast, the second class exhibited attenuated firing rates, but only at the reward epoch of the task. These findings suggest that some NAcc neurons play a role in reward-based reinforcement during learning. C1 [Gale, John T.; Shields, Donald C.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Nayef Al Rodhan Lab Cellular Neurosurg & Neurosur, Dept Neurosurg,Med Sch, Boston, MA 02114 USA. [Ishizawa, Yumiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Critical Care & Pain Med, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Wang Ambulatory Care Ctr, 331,15 Parkman St, Boston, MA 02114 USA. EM eeskandar@partners.org FU National Science Foundation [JOB 0645886]; National Institutes of Health [NET 1R01EY017658-01A1, NIDA 1R01N5063249, NIMH MH086400]; Howard Hughes Medical Institute FX This work was supported by grants from the National Science Foundation (JOB 0645886), the National Institutes of Health (NET 1R01EY017658-01A1, NIDA 1R01N5063249, NIMH Conte Award MH086400) and the Howard Hughes Medical Institute. Dr. Gale's current address is the NC-30, 9500 Euclid Avenue, Department of Neuroscience, Cleveland Clinic, Cleveland, OH 44195. Dr. Shield's current address is 2150 Pennsylvania Ave., NW, Ste. 7-420, Washington, DC 20037. NR 50 TC 3 Z9 3 U1 1 U2 14 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PD APR 3 PY 2014 VL 8 DI 10.3389/fnbeh.2014.00114 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AE0QO UT WOS:000333671300001 ER PT J AU Polyak, K Marusyk, A AF Polyak, Kornelia Marusyk, Andriy TI CANCER Clonal cooperation SO NATURE LA English DT Editorial Material ID DIVERSITY C1 [Polyak, Kornelia; Marusyk, Andriy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Polyak, Kornelia; Marusyk, Andriy] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu NR 10 TC 11 Z9 12 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 3 PY 2014 VL 508 IS 7494 BP 52 EP 53 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD9UL UT WOS:000333609900040 PM 24695309 ER PT J AU Chen, X Iliopoulos, D Zhang, Q Tang, QZ Greenblatt, MB Hatziapostolou, M Lim, E Tam, WL Ni, M Chen, YW Mai, JH Shen, HF Hu, DZ Adoro, S Hu, B Song, MY Tan, C Landis, MD Ferrari, M Shin, SJ Brown, M Chang, JC Liu, XS Glimcher, LH AF Chen, Xi Iliopoulos, Dimitrios Zhang, Qing Tang, Qianzi Greenblatt, Matthew B. Hatziapostolou, Maria Lim, Elgene Tam, Wai Leong Ni, Min Chen, Yiwen Mai, Junhua Shen, Haifa Hu, Dorothy Z. Adoro, Stanley Hu, Bella Song, Minkyung Tan, Chen Landis, Melissa D. Ferrari, Mauro Shin, Sandra J. Brown, Myles Chang, Jenny C. Liu, X. Shirley Glimcher, Laurie H. TI XBP1 promotes triple-negative breast cancer by controlling the HIF1 alpha pathway SO NATURE LA English DT Article ID UNFOLDED PROTEIN RESPONSE; STEM-CELLS; STRESS-RESPONSE; ER STRESS; HYPOXIA; METASTASIS; TUMORS; GENERATION; PHENOTYPE; CARCINOMA AB Cancer cells induce a set of adaptive response pathways to survive in the face of stressors due to inadequate vascularization(1). One such adaptive pathway is the unfolded protein(UPR) or endoplasmic reticulum (ER) stress response mediated in part by the ER-localized transmembrane sensor IRE1 (ref. 2) and its substrate XBP1 (ref. 3). Previous studies report UPR activation in various human tumours(4-6), but the role of XBP1 in cancer progression in mammary epithelial cells is largely unknown. Triple-negative breast cancer (TNBC)-a form of breast cancer in which tumour cells do not express the genes for oestrogen receptor, progesterone receptor and HER2 (also called ERBB2 or NEU)-is a highly aggressive malignancy with limited treatment options(7,8). Here we report that XBP1 is activated in TNBC and has a pivotal role in the tumorigenicity and progression of this human breast cancer subtype. In breast cancer cell line models, depletion of XBP1 inhibited tumour growth and tumour relapse and reduced the CD44(high)CD24(low) population. Hypoxia-inducing factor 1 alpha (HIF1 alpha) is known to be hyperactivated in TNBCs9,10. Genome-wide mapping of the XBP1 transcriptional regulatory network revealed that XBP1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1 alpha that regulates the expression of HIF1 alpha targets via the recruitment of RNA polymerase II. Analysis of independent cohorts of patients with TNBC revealed a specific XBP1 gene expression signature that was highly correlated with HIF1 alpha and hypoxia-driven signatures and that strongly associated with poor prognosis. Our findings reveal a key function for the XBP1 branch of the UPR in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer. C1 [Chen, Xi; Adoro, Stanley; Song, Minkyung; Tan, Chen; Glimcher, Laurie H.] Weill Cornell Med Coll, Sandra & Edward Meyer Canc Ctr, New York, NY 10065 USA. [Chen, Xi; Adoro, Stanley; Song, Minkyung; Tan, Chen; Ferrari, Mauro; Chang, Jenny C.; Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Iliopoulos, Dimitrios; Hatziapostolou, Maria] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Syst Biomed, Los Angeles, CA 90095 USA. [Iliopoulos, Dimitrios; Hatziapostolou, Maria] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Zhang, Qing] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Tang, Qianzi] Tongji Univ, Dept Bioinformat, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. [Tang, Qianzi] Sichuan Agr Univ, Coll Anim Sci & Technol, Inst Anim Genet & Breeding, Yaan 625014, Sichuan, Peoples R China. [Greenblatt, Matthew B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lim, Elgene; Ni, Min; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lim, Elgene; Ni, Min; Brown, Myles] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Tam, Wai Leong] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Chen, Yiwen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chen, Yiwen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mai, Junhua; Shen, Haifa; Ferrari, Mauro] Houston Methodist Res Inst, Dept Nanomed, Houston, TX 77030 USA. [Shen, Haifa] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA. [Hu, Dorothy Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Hu, Bella] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Landis, Melissa D.; Chang, Jenny C.] Houston Methodist Canc Ctr, Houston, TX 77030 USA. [Shin, Sandra J.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. RP Glimcher, LH (reprint author), Weill Cornell Med Coll, Sandra & Edward Meyer Canc Ctr, 1300 York Ave, New York, NY 10065 USA. EM lglimche@med.cornell.edu RI Hatziapostolou, Maria/N-1820-2015; chang, jenny/G-7614-2015; OI Hatziapostolou, Maria/0000-0003-2493-7028; Lim, Elgene/0000-0001-8065-8838; chang, jenny/0000-0002-0890-9302; Chen, Xi/0000-0002-7995-6202; Mai, Junhua/0000-0001-8374-4352; Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health [CA112663, AI32412, R01HG004069, K99CA175290]; Leukemia and Lymphoma Society; National Natural Science Foundation of China [NSFC31329003] FX We thank W. G. Kaelin, A.-H. Lee, F. Martinon, M. N. Wein and X. Li for critical review of the manuscript. We are grateful to A. L. Richardson, H. Xu and J. Wang for advice and discussions. We thank L. A. Paskett, X. Liu, R. Kim and Y. Liu for technical support. This work was supported by the National Institutes of Health (CA112663 and AI32412 to L. H. G.; R01HG004069 to X. S. L.; K99CA175290 to Y. C.), the Leukemia and Lymphoma Society (to X. C.) and the National Natural Science Foundation of China (NSFC31329003 to X.S.L.). NR 30 TC 140 Z9 147 U1 16 U2 116 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 3 PY 2014 VL 508 IS 7494 BP 103 EP + DI 10.1038/nature13119 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AD9UL UT WOS:000333609900051 PM 24670641 ER PT J AU Huggett, MT Jermyn, M Gillams, A Illing, R Mosse, S Novelli, M Kent, E Bown, SG Hasan, T Pogue, BW Pereira, SP AF Huggett, M. T. Jermyn, M. Gillams, A. Illing, R. Mosse, S. Novelli, M. Kent, E. Bown, S. G. Hasan, T. Pogue, B. W. Pereira, S. P. TI Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE photodynamic therapy; verteporfin; pancreatic adenocarcinoma ID IRREVERSIBLE ELECTROPORATION; PLUS GEMCITABINE; III TRIAL; TUMOR; ADENOCARCINOMA; SURVIVAL; MULTICENTER; ABLATION; OUTCOMES; MODELS AB Background: Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin. Methods: Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4mg kg(-1) verteporfin. After 60-90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12mm of necrosis was achieved consistently. Results: In all, 12mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm(3) at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy. Conclusions: Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds. C1 [Huggett, M. T.; Pereira, S. P.] UCL, Royal Free Hosp, Sch Med, Inst Liver & Digest Hlth, London NW3 2QG, England. [Jermyn, M.; Pogue, B. W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Gillams, A.; Illing, R.] Univ Coll Hosp, Dept Radiol, London, England. [Mosse, S.; Bown, S. G.] UCL, Natl Med Laser Ctr, London, England. [Novelli, M.] Univ Coll Hosp, Dept Pathol, London, England. [Kent, E.] Univ Coll Hosp, UCLH Canc Clin Trials Unit, London, England. [Hasan, T.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pereira, SP (reprint author), UCL, Royal Free Hosp, Sch Med, Inst Liver & Digest Hlth, Campus U3 Floor,Pond St, London NW3 2QG, England. EM stephen.pereira@ucl.ac.uk FU NIH [P01 CA084203]; Killing Cancer; UCLH Charitable Foundation; UCLH/UCL Comprehensive Biomedical Centre; Health's National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme FX We would like to thank the patients, and their families, without whom this trial would not have been possible. We also thank the UCL Joint Research Office for facilitating the conduct of the study, and the independent data monitoring committee (Professor Hugh Barr (Chair), Mr Hemant Kocher, and Dr Gary Middleton). This work was supported by NIH grant P01 CA084203, Killing Cancer and the UCLH Charitable Foundation. It was also partly supported by the UCLH/UCL Comprehensive Biomedical Centre which receives a proportion of funding from the Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme. NR 37 TC 47 Z9 48 U1 7 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 2 PY 2014 VL 110 IS 7 BP 1698 EP 1704 DI 10.1038/bjc.2014.95 PG 7 WC Oncology SC Oncology GA AF1TD UT WOS:000334495700003 PM 24569464 ER PT J AU Guo, S Lopez-Marquez, H Fan, KC Choy, E Cote, G Harmon, D Nielsen, GP Yang, C Zhang, CQ Mankin, H Hornicek, FJ Borger, DR Duan, ZF AF Guo, Shang Lopez-Marquez, Hector Fan, Kenneth C. Choy, Edwin Cote, Gregory Harmon, David Nielsen, G. Petur Yang, Cao Zhang, Changqing Mankin, Henry Hornicek, Francis J. Borger, Darrell R. Duan, Zhenfeng TI Synergistic Effects of Targeted PI3K Signaling Inhibition and Chemotherapy in Liposarcoma SO PLOS ONE LA English DT Article ID DEDIFFERENTIATED LIPOSARCOMA; LIPOMATOUS TUMORS; EXPRESSION; DIAGNOSIS; PATHWAY; CANCER; MDM2; CDK4; OSTEOSARCOMA; ACTIVATION AB While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%). No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma. C1 [Guo, Shang; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Guo, Shang; Zhang, Changqing] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Shanghai 200030, Peoples R China. [Lopez-Marquez, Hector; Fan, Kenneth C.; Borger, Darrell R.] Massachusetts Gen Hosp, Translat Res Lab, Boston, MA 02114 USA. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yang, Cao] Huazhong Univ Sci & Technol, Union Hosp, Dept Orthopaed, Wuhan 430074, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu OI Cote, Gregory/0000-0003-0181-886X FU Jeff Guyer Fund; Gattegno fund; Wechsler fund; Kenneth Stanton Fund; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [CA 151452-01]; Academic Enrichment Fund of MGH Orthopaedics FX This project was supported, in part, by grants from the Jeff Guyer Fund. Support has also been provided by the Gattegno and Wechsler funds, the Kenneth Stanton Fund. ZD is supported, in part, through a grant from Sarcoma Foundation of America (SFA), a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452-01, and a grant from an Academic Enrichment Fund of MGH Orthopaedics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 9 Z9 9 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 2 PY 2014 VL 9 IS 4 AR e93996 DI 10.1371/journal.pone.0093996 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AE6LC UT WOS:000334103000133 PM 24695632 ER PT J AU Young, KA Franklin, TR Roberts, DCS Jagannathan, K Suh, JJ Wetherill, RR Wang, Z Kampman, KM O'Brien, CP Childress, AR AF Young, Kimberly A. Franklin, Teresa R. Roberts, David C. S. Jagannathan, Kanchana Suh, Jesse J. Wetherill, Reagan R. Wang, Ze Kampman, Kyle M. O'Brien, Charles P. Childress, Anna Rose TI Nipping Cue Reactivity in the Bud: Baclofen Prevents Limbic Activation Elicited by Subliminal Drug Cues SO JOURNAL OF NEUROSCIENCE LA English DT Article DE addiction; baclofen; cocaine; cues; fMRI; subliminal ID COCAINE-SEEKING BEHAVIOR; CONDITIONED DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; DEPENDENT INDIVIDUALS; INTRATHECAL BACLOFEN; RATS; ADDICTION; AMYGDALA; MOTIVATION; METAANALYSIS AB Relapse is a widely recognized and difficult to treat feature of the addictions. Substantial evidence implicates cue-triggered activation of the mesolimbic dopamine system as an important contributing factor. Even drug cues presented outside of conscious awareness (i.e., subliminally) produce robust activation within this circuitry, indicating the sensitivity and vulnerability of the brain to potentially problematic reward signals. Because pharmacological agents that prevent these early cue-induced responses could play an important role in relapse prevention, we examined whether baclofen-a GABA(B) receptor agonist that reduces mesolimbic dopamine release and conditioned drug responses in laboratory animals-could inhibit mesolimbic activation elicited by subliminal cocaine cues in cocaine-dependent individuals. Twenty cocaine-dependent participants were randomized to receive baclofen (60 mg/d; 20 mg t.i.d.) or placebo. Event-related BOLD fMRI and a backward-masking paradigm were used to examine the effects of baclofen on subliminal cocaine (vs neutral) cues. Sexual and aversive cues were included to examine specificity. We observed that baclofen-treated participants displayed significantly less activation in response to subliminal cocaine (vs neutral) cues, but not sexual or aversive (vs neutral) cues, than placebo-treated participants in a large interconnected bilateral cluster spanning the ventral striatum, ventral pallidum, amygdala, midbrain, and orbitofrontal cortex (voxel threshold p < 0.005; cluster corrected at p < 0.05). These results suggest that baclofen may inhibit the earliest type of drug cue-induced motivational processing-that which occurs outside of awareness-before it evolves into a less manageable state. C1 [Young, Kimberly A.; Franklin, Teresa R.; Jagannathan, Kanchana; Suh, Jesse J.; Wetherill, Reagan R.; Wang, Ze; Kampman, Kyle M.; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Roberts, David C. S.] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. [Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Childress, AR (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM childres@mail.med.upenn.edu OI Roberts, David/0000-0001-7040-0155 FU National Institutes of Health [T32 DA029974, R01 DA010241, P50 DA12756]; Commonwealth of Pennsylvania CURE Addiction Center of Excellence FX This work was supported by National Institutes of Health Grants T32 DA029974, R01 DA010241, and P50 DA12756, and the Commonwealth of Pennsylvania CURE Addiction Center of Excellence. We thank the research and clinical staff and nurses at the Center for Studies of Addictions, for their expert assistance throughout the study, the technical staff at the University of Pennsylvania Center for Functional Neuroimaging, and Yin Li, for assistance with image processing. We also thank the National Institute on Drug Abuse for providing the study medication. NR 40 TC 14 Z9 14 U1 1 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 2 PY 2014 VL 34 IS 14 BP 5038 EP 5043 DI 10.1523/JNEUROSCI.4977-13.2014 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AE6CL UT WOS:000334076000027 PM 24695721 ER PT J AU Walter, LC Schonberg, MA AF Walter, Louise C. Schonberg, Mara A. TI Screening Mammography in Older Women A Review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID BREAST-CANCER RISK; CARCINOMA IN-SITU; ESTROGEN PLUS PROGESTIN; HORMONE-RECEPTOR STATUS; REPLACEMENT THERAPY USE; SERVICES TASK-FORCE; AGE 80 YEARS; POSTMENOPAUSAL WOMEN; DECISION-MAKING; UNITED-STATES AB IMPORTANCE Guidelines recommend individualizing screening mammography decisions for women aged 75 years and older. However, little pragmatic guidance is available to help counsel patients. OBJECTIVE To provide an evidence-based approach for individualizing decision-making about screening mammography in older women. E EVIDENCE ACQUISITION We searched PubMed for English-language studies in peer-reviewed journals published from January 1,1990, to February 1, 2014, to identify risk factors for late-life breast cancer in women aged 65 years and older and to quantify the benefits and harms of screening mammography for women aged 75 years and older. FINDINGS Age is the major risk factor for developing and dying from breast cancer. Breast cancer risk factors that reflect hormonal exposures in the distant past, such as age at first birth or age at menarche, are less predictive of late-life breast cancer than factors indicating recent hormonal exposures such as high bone mass or obesity. Randomized trials of the benefits of screening mammography did not include women older than 74 years. Thus it is not known if screening mammography benefits older women. Observational studies favor extending screening mammography to older women who have a life expectancy of more than 10 years. Modeling studies estimate 2 fewer breast cancer deaths/1000 women who in their 70s continue biennial screening for 10 years instead of stopping screening at age 69. Potential harms of continued screening over 10 years include false-positive mammograms in approximately 200/1000 women screened and overdiagnosis (ie, finding breast cancer that would not have clinically surfaced otherwise) in approximately 13/1000 women screened. Providing information about life expectancy along with potential benefits and harms of screening may help older women's decision-making about screening mammography. CONCLUSIONS AND RELEVANCE For women with less than a 10-year life expectancy, recommendations to stop screening mammography should emphasize increased potential harms from screening and highlight health promotion measures likely to be beneficial over the short term. For women with a life expectancy of more than 10 years, deciding whether potential benefits of screening outweigh harms becomes a value judgment for patients, requiring a realistic understanding of screening outcomes. C1 [Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schonberg, Mara A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Dept Med,Med Sch, Boston, MA 02215 USA. RP Walter, LC (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr 181G, 4150 Clement St, San Francisco, CA 94121 USA. EM Louise.Walter@ucsf.edu FU National Cancer Institute [RO1 CA134425]; National Institute on Aging [K24AG041180]; Paul B. Beeson Career Development Award in Aging [K23AG028584]; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation; American Federation for Aging Research FX This work was supported by the National Cancer Institute (grant RO1 CA134425) and the National Institute on Aging (grant K24AG041180) (Dr Walter); the Paul B. Beeson Career Development Award in Aging (grant K23AG028584) (Dr Schonberg); as well as support from the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation, and the American Federation for Aging Research. NR 98 TC 43 Z9 43 U1 1 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2014 VL 311 IS 13 BP 1336 EP 1347 DI 10.1001/jama.2014.2834 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AE0HU UT WOS:000333645400017 PM 24691609 ER PT J AU Li, ZP Heber, D AF Li, Zhaoping Heber, David TI Managing Weight Loss Expectations The Challenge and the Opportunity SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID GASTRIC BYPASS-SURGERY; BARIATRIC SURGERY; MORTALITY; OUTCOMES; RISK AB IMPORTANCE: Weight loss surgery (WLS) has been shown to produce long-term weight loss but is not risk free or universally effective. The weight loss expectations and willingness to undergo perioperative risk among patients seeking WLS remain unknown. OBJECTIVES: To examine the expectations and motivations of WLS patients and the mortality risks they are willing to undertake and to explore the demographic characteristics, clinical factors, and patient perceptions associated with high weight loss expectations and willingness to assume high surgical risk. DESIGN: We interviewed patients seeking WLS and conducted multivariable analyses to examine the characteristics associated with high weight loss expectations and the acceptance of mortality risks of 10% or higher. SETTING: Two WLS centers in Boston. PARTICIPANTS: Six hundred fifty-four patients. MAIN OUTCOME MEASURES: Disappointment with a sustained weight loss of 20% and willingness to accept a mortality risk of 10% or higher with WLS. RESULTS: On average, patients expected to lose as much as 38% of their weight after WLS and expressed disappointment if they did not lose at least 26%. Most patients (84.8%) accepted some risk of dying to undergo WLS, but only 57.5% were willing to undergo a hypothetical treatment that produced a 20% weight loss. The mean acceptable mortality risk to undergo WLS was 6.7%, but the median risk was only 0.1%; 19.5% of all patients were willing to accept a risk of at least 10%. Women were more likely than men to be disappointed with a 20% weight loss but were less likely to accept high mortality risk. After initial adjustment, white patients appeared more likely than African American patients to have high weight loss expectations and to be willing to accept high risk. Patients with lower quality-of-life scores and those who perceived needing to lose more than 10% and 20% of weight to achieve "any" health benefits were more likely to have unrealistic weight loss expectations. Low quality-of-life scores were also associated with willingness to accept high risk. CONCLUSIONS AND RELEVANCE: Most patients seeking WLS have high weight loss expectations and believe they need to lose substantial weight to derive any health benefits. Educational efforts may be necessary to align expectations with clinical reality. C1 [Li, Zhaoping; Heber, David] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. [Li, Zhaoping] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Heber, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, 900 Vet Ave, Los Angeles, CA 90095 USA. EM dheber@mednet.ucla.edu NR 10 TC 0 Z9 0 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2014 VL 311 IS 13 BP 1348 EP 1349 DI 10.1001/jamasurg.2013.1048 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AE0HU UT WOS:000333645400018 PM 24691610 ER PT J AU Anderson, TS Dave, S Good, CB Gellad, WF AF Anderson, Timothy S. Dave, Shravan Good, Chester B. Gellad, Walid F. TI Academic Medical Center Leadership on Pharmaceutical Company Boards of Directors SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Anderson, Timothy S.] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA USA. [Dave, Shravan] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Good, Chester B.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 151C Univ Dr, Pittsburgh, PA 15240 USA. EM wfg3@pitt.edu NR 6 TC 6 Z9 6 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2014 VL 311 IS 13 BP 1353 EP 1355 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AE0HU UT WOS:000333645400020 PM 24691612 ER PT J AU Falcone, GJ Malik, R Dichgans, M Rosand, J AF Falcone, Guido J. Malik, Rainer Dichgans, Martin Rosand, Jonathan TI Current concepts and clinical applications of stroke genetics SO LANCET NEUROLOGY LA English DT Review ID GENOME-WIDE ASSOCIATION; CEREBRAL AMYLOID ANGIOPATHY; CORONARY-ARTERY-DISEASE; LOBAR INTRACEREBRAL HEMORRHAGE; MATTER HYPERINTENSITY VOLUME; BETA PRECURSOR PROTEIN; ACUTE ISCHEMIC-STROKE; SMALL-VESSEL DISEASE; ATRIAL-FIBRILLATION; RISK-FACTORS AB Driven by innovative technologies, novel analytical methods, and collaborations unimaginable not long ago, our understanding of the role of genetic variation in stroke has advanced substantially in recent years. However, a vast amount of data have accumulated quickly, and increasingly complex methodologies used in studies make keeping up to date on relevant findings difficult. In addition to well known, highly penetrant rare mutations that cause mendelian disorders related to stroke, several common genetic variants have been associated with common stroke subtypes, some of which also affect disease severity and clinical outcome. Furthermore, common genetic variations in biological pathways that have an important role in the pathophysiology of cerebrovascular diseases-such as blood pressure and oxidative phosphorylation-have been implicated in stroke. Clinical and translational applications of these and future discoveries in stroke genetics include identification of novel targets for treatment and development of personalised approaches to stroke prevention and management. C1 [Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Falcone, Guido J.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Falcone, Guido J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Malik, Rainer; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jrosand@partners.org RI Falcone, Guido/L-2287-2016 OI Falcone, Guido/0000-0002-6407-0302 FU NIH; National Institute for Neurological Disorders and Stroke (NINDS) [R01NS059727, P50NS061343]; NIH-NINDS SPOTRIAS fellowship grant [P50NS061343] FX Our work has been supported by the NIH and the National Institute for Neurological Disorders and Stroke (NINDS), grants R01NS059727 and P50NS061343. GJF was supported by the NIH-NINDS SPOTRIAS fellowship grant P50NS061343. NR 148 TC 26 Z9 26 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2014 VL 13 IS 4 BP 405 EP 418 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA CB6NN UT WOS:000349743800012 PM 24646874 ER PT J AU Greenberg, SM Salman, RAS Biessels, GJ van Buchem, M Cordonnier, C Lee, JM Montaner, J Schneider, JA Smith, EE Vernooij, M Werring, DJ AF Greenberg, Steven M. Salman, Rustam Al-Shahi Biessels, Geert Jan van Buchem, Mark Cordonnier, Charlotte Lee, Jin-Moo Montaner, Joan Schneider, Julie A. Smith, Eric E. Vernooij, Meike Werring, David J. TI Outcome markers for clinical trials in cerebral amyloid angiopathy SO LANCET NEUROLOGY LA English DT Review ID WHITE-MATTER LESIONS; SMALL-VESSEL DISEASE; AUSTRIAN STROKE PREVENTION; TRANSIENT ISCHEMIC ATTACK; LOBAR INTRACEREBRAL HEMORRHAGE; CORTICAL SUPERFICIAL SIDEROSIS; ENLARGED PERIVASCULAR SPACES; APOLIPOPROTEIN-E GENOTYPE; COGNITIVE FUNCTION; BOSTON CRITERIA AB Efforts are underway for early-phase trials of candidate treatments for cerebral amyloid angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for cerebral amyloid angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for cerebral amyloid angiopathy trials are probably applicable also to other small-vessel brain diseases. C1 [Greenberg, Steven M.] Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. [Salman, Rustam Al-Shahi] Univ Edinburgh, Ctr Clin Brain Sci, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Biessels, Geert Jan] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [van Buchem, Mark] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Cordonnier, Charlotte] Univ Lille Nord France, Lille Univ Hosp, EA 1046, Dept Neurol, Lille, France. [Lee, Jin-Moo] Washington Univ, Sch Med, Dept Neurol, Dept Radiol, St Louis, MO 63110 USA. [Lee, Jin-Moo] Washington Univ, Sch Med, Dept Biomed Engn, St Louis, MO USA. [Lee, Jin-Moo] Washington Univ, Sch Med, Dept Biomed Engn, St Louis, MO USA. [Montaner, Joan] Autonomous Univ Barcelona, Vall Hebron Univ Hosp, Dept Neurol, Barcelona, Spain. [Montaner, Joan] Autonomous Univ Barcelona, Vall Hebron Univ Hosp, Res Inst, Barcelona, Spain. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Vernooij, Meike] Erasmus Univ, Med Ctr, Dept Radiol & Epidemiol, Rotterdam, Netherlands. [Werring, David J.] UCL, Inst Neurol, London, England. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, Dept Neurol, 175 Cambridge St, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Lee, Jin-Moo/K-2024-2015; Smith, Eric/C-5443-2012; Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015 OI Lee, Jin-Moo/0000-0002-3979-0906; Smith, Eric/0000-0003-3956-1668; FU National Institutes of Health [R01 AG26484, R01 NS070834, R01 NS067905]; Medical Research Council; Netherlands Organization for Health Research and Development (ZonMw Vidi grant) [91711384]; Netherlands Heart Foundation [2010T073]; Erasmus MC Clinical Fellowship; Department of Health's National Institute for Health Research Biomedical Research Centres FX We thank Susanne van Veluw, M Edip Gurol and Panos Fotiadis for assistance with figures. SMG is funded by the National Institutes of Health (R01 AG26484, R01 NS070834). RA-SS is funded by a Medical Research Council senior clinical fellowship. GJB is funded by the Netherlands Organization for Health Research and Development (ZonMw Vidi grant 91711384) and the Netherlands Heart Foundation (grant 2010T073). J-ML is funded by the National Institutes of Health (R01 NS067905). MV is funded by an Erasmus MC Clinical Fellowship. DJW's centre receives funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. NR 99 TC 42 Z9 44 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2014 VL 13 IS 4 BP 419 EP 428 DI 10.1016/S1474-4422(14)70003-1 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CB6NN UT WOS:000349743800013 PM 24581702 ER PT J AU Durbin, CG Blanch, L Fan, E Hess, DR AF Durbin, Charles G., Jr. Blanch, Lluis Fan, Eddy Hess, Dean R. TI Respiratory Care Year in Review 2013: Airway Management, Noninvasive Monitoring, and Invasive Mechanical Ventilation SO RESPIRATORY CARE LA English DT Review DE extubation; high-frequency oscillatory ventilation; intubation; lung-protective ventilation; mechanical ventilation; respiratory mechanics; tracheostomy ID ACUTE LUNG INJURY; END-EXPIRATORY PRESSURE; HIGH-FREQUENCY OSCILLATION; RANDOMIZED CONTROLLED-TRIAL; DISTRESS-SYNDROME; CARDIOPULMONARY-RESUSCITATION; DIFFICULT AIRWAY; LATE TRACHEOTOMY; CARDIAC-ARREST; TIDAL VOLUMES AB Fundamental to respiratory care practice are airway management, noninvasive monitoring, and invasive mechanical ventilation. The purpose of this paper is to review the recent literature related to these topics in a manner that is most likely to have interest to the readers of RESPIRATORY CARE. C1 [Durbin, Charles G., Jr.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. [Blanch, Lluis] Univ Autonoma Barcelona, Hosp Univ Corp Sanitaria Parc Tauli Sabadel, Madrid, Spain. [Blanch, Lluis] Inst Salud Carlos III ISCIII, CIBERES, Madrid, Spain. [Fan, Eddy] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Dept, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 69 TC 4 Z9 4 U1 2 U2 9 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD APR PY 2014 VL 59 IS 4 BP 595 EP 606 DI 10.4187/respcare.03199 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CA8VR UT WOS:000349199500019 PM 24713763 ER PT J AU McClintock, TR Chen, Y Parvez, F Makarov, DV Ge, WZ Islam, T Ahmed, A Rakibuz-Zaman, M Hasan, R Sarwar, G Slavkovich, V Bjurlin, MA Graziano, JH Ahsan, H AF McClintock, Tyler R. Chen, Yu Parvez, Faruque Makarov, Danil V. Ge, Wenzhen Islam, Tariqul Ahmed, Alauddin Rakibuz-Zaman, Muhammad Hasan, Rabiul Sarwar, Golam Slavkovich, Vesna Bjurlin, Marc A. Graziano, Joseph H. Ahsan, Habibul TI Association between arsenic exposure from drinking water and hematuria: Results from the Health Effects of Arsenic Longitudinal Study SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Arsenic; Bangladesh; Environmental epidemiology; Hematuria; Mass screening; Urologic neoplasms ID ASYMPTOMATIC MICROSCOPIC HEMATURIA; DISEASE ENDEMIC AREA; KIDNEY CANCER; BLADDER-CANCER; MALIGNANT NEOPLASMS; WELL WATER; MORTALITY; RISK; BANGLADESH; TAIWAN AB Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04-1.59), 1.41 (95% CI: 1.15-1.74), 1.46 (95% CI: 1.19-1.79), and 1.56 (95% CI: 1.27-1.91). Compared to those with relatively little absolute urinary As change during follow-up (-10.40 to 41.17 mu g/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80-1.22) and 0.80(95% CI: 0.65-0.99) for those whose urinary As decreased by >47.49 mu g/l and 10.87 to 47.49 mu g/l since last visit, respectively, and 1.17 (95% CI: 0.94-1.45) and 1.36(95% CI: 1.10-1.66) for those with between-visit increases of 10.40 to 41.17 mu g/l and >41.17 mu g/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As. (C) 2014 Elsevier Inc. All rights reserved. C1 [McClintock, Tyler R.; Chen, Yu; Ge, Wenzhen] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [McClintock, Tyler R.; Chen, Yu; Ge, Wenzhen] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA. [McClintock, Tyler R.; Makarov, Danil V.; Bjurlin, Marc A.] NYU, Sch Med, Dept Urol, New York, NY 10016 USA. [Parvez, Faruque; Slavkovich, Vesna; Graziano, Joseph H.] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. [Makarov, Danil V.] NYU, Robert F Wagner Grad Sch Publ Serv, New York, NY 10016 USA. [Makarov, Danil V.] US Dept Vet Affairs, Harbor Healthcare Syst, New York, NY USA. [Makarov, Danil V.] NYU, Inst Canc, New York, NY 10016 USA. [Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam] U Chicago Res Bangladesh Ltd, Dhaka, Bangladesh. [Ahsan, Habibul] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Ahsan, Habibul] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA. RP Chen, Y (reprint author), NYU, Sch Med, Dept Populat Hlth, 650 First Ave, New York, NY 10016 USA. EM yu.chen@nyumc.org; habib@uchicago.edu OI Makarov, Danil/0000-0002-0565-9272 FU National Institutes of Health [R01 ES017541, R01 CA107431, P42 ES010349, P30 ES000260]; National Center for the Advancement of Translational Science (NCATS), National Institutes of Health [UL1 TR000038] FX This work was supported by the National Institutes of Health (grants R01 ES017541, R01 CA107431, P42 ES010349, and P30 ES000260) and in part by grant UL1 TR000038 from the National Center for the Advancement of Translational Science (NCATS), National Institutes of Health. NR 37 TC 4 Z9 5 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 1 PY 2014 VL 276 IS 1 BP 21 EP 27 DI 10.1016/j.taap.2014.01.015 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CA9XS UT WOS:000349278700002 PM 24486435 ER PT J AU Tolaney, SM Jeong, J Guo, H Brock, J Morganstern, D Come, SE Golshan, M Bellon, J Winer, EP Krop, IE AF Tolaney, Sara M. Jeong, Joon Guo, Hao Brock, Jane Morganstern, Daniel Come, Steven E. Golshan, Mehra Bellon, Jennifer Winer, Eric P. Krop, Ian E. TI A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer SO CANCER MEDICINE LA English DT Article DE Breast; cancer; capecitabine; chemotherapy; preoperative ID THYMIDINE PHOSPHORYLASE EXPRESSION; NEOADJUVANT CHEMOTHERAPY; PLUS IRINOTECAN; DOCETAXEL; CYCLOPHOSPHAMIDE; METHOTREXATE; THERAPY; CELLS; TRIAL AB Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m(2) daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller-Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer. C1 [Tolaney, Sara M.; Morganstern, Daniel; Winer, Eric P.; Krop, Ian E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jeong, Joon] Yonsei Univ, Gangnam Severance Hosp, Dept Surg, Seoul 120749, South Korea. [Guo, Hao] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brock, Jane] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Morganstern, Daniel] Faulkner Hosp, Dept Med Oncol, Boston, MA USA. [Come, Steven E.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Bellon, Jennifer] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Bellon, Jennifer] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tolaney, SM (reprint author), 450 Brookline Ave,Yawkey 1257, Boston, MA 02215 USA. EM stolaney@partners.org RI Guo, Hao/E-8921-2015; OI Guo, Hao/0000-0003-1658-0989; Jeong, Joon/0000-0003-0397-0005 FU Breast Cancer Research Foundation FX This research was supported by a grant from the Breast Cancer Research Foundation. NR 25 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD APR PY 2014 VL 3 IS 2 BP 293 EP 299 DI 10.1002/cam4.164 PG 7 WC Oncology SC Oncology GA AZ4WG UT WOS:000348220600009 PM 24464780 ER PT J AU Johnson, LL Delano, M Spector, M Pittsley, A Gottschalk, A AF Johnson, Lanny Leo Delano, Mark Spector, Myron Pittsley, Andrew Gottschalk, Alexander TI The Long-Term Clinical Outcomes Following Autogenous Bone Grafting for Large-Volume Defects of the Knee: 12-to 21-Year Follow-Up SO CARTILAGE LA English DT Article DE knee; arthroscopy; cartilage repair; matrices ID AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; FULL-THICKNESS DEFECTS; ARTICULAR-CARTILAGE; OSTEOCHONDRITIS-DISSECANS; REPAIR; OSTEONECROSIS; INJURY; OSTEOARTHRITIS; ARTHROPLASTY; SECONDARY AB Objective: We report the long-term clinical outcomes of patients who underwent autogenous bone grafting of large-volume osteochondral defects of the knee due to osteochondritis dessicans (OCD) and osteonecrosis (ON). This is the companion report to one previous published on the biological response. We hypothesized that these grafts would integrate with host bone and the articular surface would form fibrocartilage providing an enduring clinical benefit. Design: Three groups (patients/knees) were studied: OCD without a fragment (n = 12/13), OCD with a partial fragment (n = 14/16), and ON (n = 25/26). Twenty-five of 52 patients were available for clinical follow-up between 12 and 21 years. Electronic medical records provided comparison clinical information. In addition, there were plain film radiographs, MRIs, plus repeat arthroscopy and biopsy on 14 patients. Results: Autogenous bone grafts integrated with the host bone. MRI showed soft tissue covering all the grafts at long-term follow-up. Biopsy showed initial surface fibrocartilage that subsequently converted to fibrocartilage and hyaline cartilage at 20 years. OCD patients had better clinical outcomes than ON patients. No OCD patients were asymptomatic at anytime following surgery. Half of the ON patients came to total knee replacement within 10 years. Conclusions: Autogenous bone grafting provides an alternative biological matrix to fill large-volume defects in the knee as a singular solution integrating with host bone and providing an enduring articular cartilage surface. The procedure is best suited for those with OCD. The treatment for large-volume articular defects by this method remains salvage in nature and palliative in outcome. C1 [Johnson, Lanny Leo] Scripps Hlth, Okemos, MI 48864 USA. [Delano, Mark; Pittsley, Andrew; Gottschalk, Alexander] Michigan State Univ, Grand Rapids, MI USA. [Spector, Myron] Brigham & Womens Hosp, VA Boston Healthcare, Boston, MA 02115 USA. [Spector, Myron] Harvard Univ, Boston, MA 02115 USA. RP Johnson, LL (reprint author), Scripps Hlth, 4658 Chippewa Dr, Okemos, MI 48864 USA. EM lljmd@aol.com OI DeLano, Mark/0000-0003-1550-6445 NR 36 TC 4 Z9 4 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD APR PY 2014 VL 5 IS 2 BP 86 EP 96 DI 10.1177/1947603513518216 PG 11 WC Orthopedics SC Orthopedics GA AZ7ZM UT WOS:000348434400003 PM 26069688 ER PT J AU Foldager, CB Toh, WS Gomoll, AH Olsen, BR Spector, M AF Foldager, Casper Bindzus Toh, Wei Seong Gomoll, Andreas H. Olsen, Bjorn Reino Spector, Myron TI Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues SO CARTILAGE LA English DT Article DE cartilage; pericellular matrix; laminin; collagen type IV; immunohistochemistry ID NUCLEUS PULPOSUS CELLS; ARTICULAR-CARTILAGE; CHONDROCYTE ADHESION; VI COLLAGEN; EXPRESSION; INTEGRINS; OSTEOARTHRITIS; FIBRONECTIN; COMPONENTS AB Objective. The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM. C1 [Foldager, Casper Bindzus; Toh, Wei Seong; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped, Boston, MA 02115 USA. [Foldager, Casper Bindzus; Toh, Wei Seong; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA USA. [Foldager, Casper Bindzus] Aarhus Univ Hosp, Orthopaed Res Lab, DK-8000 Aarhus C, Denmark. [Toh, Wei Seong] Natl Univ Singapore, Discipline Oral Sci, Fac Dent, Singapore 117548, Singapore. [Gomoll, Andreas H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cartilage Repair Ctr, Boston, MA 02115 USA. [Olsen, Bjorn Reino] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Foldager, CB (reprint author), Aarhus Univ Hosp, Orthopaed Res Lab, Noerrebrogade 44,Bldg 1A, DK-8000 Aarhus C, Denmark. EM foldager@ki.au.dk RI Toh, Wei Seong/K-7720-2013 OI Toh, Wei Seong/0000-0001-9147-6423 FU U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service; Elite Research Scholarship from Danish Minister of Science, Technology and Innovation; A*STAR International Fellowship, Agency for Science, Technology and Research (A*STAR) Singapore; Research Career Scientist Award from Department of Veterans Affairs FX The research reported here was supported, in part, by the U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. A postdoctoral research fellowship for CBF by an Elite Research Scholarship from the Danish Minister of Science, Technology and Innovation. WST is supported by A*STAR International Fellowship, Agency for Science, Technology and Research (A*STAR) Singapore. MS is supported by a Research Career Scientist Award from the Department of Veterans Affairs. The authors would like to acknowledge research fellow Thomas Cheriyan, MD, for his technical assistance. NR 26 TC 7 Z9 7 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD APR PY 2014 VL 5 IS 2 BP 123 EP 132 DI 10.1177/1947603513518217 PG 10 WC Orthopedics SC Orthopedics GA AZ7ZM UT WOS:000348434400007 PM 26069692 ER PT J AU Whary, MT Muthupalani, S Ge, ZM Feng, Y Lofgren, J Shi, HN Taylor, NS Correa, P Versalovic, J Wang, TC Fox, JG AF Whary, Mark T. Muthupalani, Sureshkumar Ge, Zhongming Feng, Yan Lofgren, Jennifer Shi, Hai Ning Taylor, Nancy S. Correa, Pelayo Versalovic, James Wang, Timothy C. Fox, James G. TI Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota SO MICROBES AND INFECTION LA English DT Article DE Helicobacter pylori; Heligmosomoides polygyrus; Altered Schaedler Flora; INS-GAS mice; Gastric cancer ID ALTERED SCHAEDLER FLORA; HELIGMOSOMOIDES-POLYGYRUS INFECTION; C57BL/6 MICE; GASTROINTESTINAL-TRACT; DENDRITIC CELLS; TH2 RESPONSE; MOUSE MODEL; CANCER; INFLAMMATION; CARCINOGENESIS AB Higher prevalence of helminth infections in Helicobacter pylori infected children was suggested to potentially lower the life-time risk gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3(+) cells, epithelial eration, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of flammatory mRNA, helminth co-infection increased FoxP3(+) cells in the corpus and reduced H. pylori-associated gastric atrophy (p < dysplasia (p < 0.02) and prevented H. pylori-induced changes in the gastric flora (p < 0.05). This is the first evidence of helminth reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis cancer in humans. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. C1 [Whary, Mark T.; Muthupalani, Sureshkumar; Ge, Zhongming; Feng, Yan; Lofgren, Jennifer; Taylor, Nancy S.; Fox, James G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Shi, Hai Ning] Massachusetts Gen Hosp, Mucosa Immunol Lab, Boston, MA 02114 USA. [Shi, Hai Ning] Harvard Univ, Sch Med, Boston, MA USA. [Correa, Pelayo] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Versalovic, James] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Versalovic, James] Texas Childrens Hosp, Houston, TX 77030 USA. [Wang, Timothy C.] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY USA. RP Whary, MT (reprint author), 77 Mass Ave 16-825A, Cambridge, MA 02139 USA. EM mwhary@mit.edu FU National Institutes of Health [RO1-CA67529, R01DK052413, PO1CA26731, P01 CA028842, P30ESO2109, R01DK065075, R01DK082427] FX We thank Melissa Mobley and Amanda Potter who performed the necropsies and sample collection. Supported in part by RO1-CA67529, R01DK052413, PO1CA26731, P01 CA028842, P30ESO2109, R01DK065075 (JGF) and R01DK082427 (HNS) from the National Institutes of Health. NR 50 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2014 VL 16 IS 4 BP 345 EP 355 DI 10.1016/j.micinf.2014.01.005 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AY9JN UT WOS:000347866400010 PM 24513446 ER PT J AU Cho, E Townsend, M Selhub, J Paul, L Rosner, B Fuchs, C Willett, W Giovannucci, E AF Cho, Eunyoung Townsend, Mary Selhub, Jacob Paul, Ligi Rosner, Bernard Fuchs, Charles Willett, Walter Giovannucci, Edward TI Pre-diagnostic plasma unmetabolized folic acid and the risk of colorectal cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Cho, Eunyoung; Townsend, Mary; Rosner, Bernard; Willett, Walter; Giovannucci, Edward] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cho, Eunyoung; Townsend, Mary; Rosner, Bernard; Willett, Walter; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA. [Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Selhub, Jacob; Paul, Ligi] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 136.5 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700102 ER PT J AU Danial, N AF Danial, Nika TI Programming of mitochondrial fuel metabolism in the control of seizure responses SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Danial, Nika] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 474.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701188 ER PT J AU Gerszten, R AF Gerszten, Robert TI Towards the genetic architecture of the human metabolome SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Gerszten, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 350.1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700448 ER PT J AU Linderman, S Araya, J Pathan, S Nelson, D Phaneuf, M Contreras, M AF Linderman, Shannon Araya, Joel Pathan, Saif Nelson, David Phaneuf, Matthew Contreras, Mauricio TI A small diameter bioactive prosthetic vascular graft with activated protein C SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Contreras, Mauricio] BIDMC, Boston, MA USA. [Pathan, Saif; Nelson, David; Phaneuf, Matthew] Bioengn Biosurfaces, Ashland, MA USA. [Linderman, Shannon] Bioengn BU, Boston, MA USA. [Araya, Joel] North Eastern Univ, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 546.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701349 ER PT J AU Mootha, V AF Mootha, Vamsi TI Systems analysis of mitochondrial pathogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Mootha, Vamsi] Harvard Univ, Sch Med, Dept Syst Biol & Med, Boston, MA USA. [Mootha, Vamsi] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 235.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646700258 ER PT J AU Won, J Kim, J Singh, A Sharma, A Singh, I AF Won, Jeseong Kim, Jinsu Singh, Avtar Sharma, Anand Singh, Inderjit TI STAT3 regulation by S-nitrosylation: implication for inflammatory disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Won, Jeseong; Kim, Jinsu; Singh, Avtar; Sharma, Anand; Singh, Inderjit] Med Univ S Carolina, Charleston, SC 29425 USA. [Singh, Avtar] Ralph H Johnson Vet Adm Med Ctr, Pathol & Lab Med Serv, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 555.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646701390 ER PT J AU Xavier, R AF Xavier, Ramnik TI Post-translational modifications of host proteins in pathogen defense SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting CY APR 26-30, 2014 CL San Diego, CA SP Cenveo, LI COR, Wiley, Mead Johnson Pediat Nutr Inst, IPRECIO, F1000 Res, Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 [Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 98.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0MP UT WOS:000346646705197 ER PT J AU Christensen, H Damkier, H Paunescu, T Brown, D Praetorius, J AF Christensen, Henriette Damkier, Helle Paunescu, Teodor Brown, Dennis Praetorius, Jeppe TI Decreased plasma CO2 induces redistribution of the V-ATPase in the choroid plexus epithelium: involvement in regulation of cerebrospinal fluid pH? SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Christensen, Henriette; Damkier, Helle; Praetorius, Jeppe] Aarhus Univ, Aarhus C, Denmark. [Paunescu, Teodor; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Paunescu, Teodor; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1098.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651001235 ER PT J AU Coon, S Rajendran, V Singh, S AF Coon, Steven Rajendran, Vazhaikkurichi Singh, Satish TI GIP regulates glucose transporer-2 to augment jejunal glucose absorption in obese mouse prior to the onset of diabetes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Coon, Steven; Singh, Satish] Boston Univ, Dept Med, Boston, MA 02215 USA. [Coon, Steven] Boston Univ, Clin & Translat Sci Inst, Boston, MA 02215 USA. [Coon, Steven; Singh, Satish] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Rajendran, Vazhaikkurichi] W Virginia Univ, Dept Biochem & Mol Biol, Morgantown, WV 26506 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 908.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003312 ER PT J AU Davies, G Birtwistle, M Pope, M Perry, V Sacks, H Budge, H Symonds, M AF Davies, Graeme Birtwistle, Mark Pope, Mark Perry, Vivienne Sacks, Harold Budge, Helen Symonds, Michael TI The developmental transition of epicardial, paracardial and omental adipose tissue during early life in the sheep SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Davies, Graeme; Birtwistle, Mark; Pope, Mark; Budge, Helen; Symonds, Michael] Univ Nottingham, Nottingham NG7 2RD, England. [Perry, Vivienne] Univ Nottingham, Sch Vet Med & Sci, Loughborough, Leics, England. [Sacks, Harold] VA Greater Los Angeles Healthcare, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1160.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002192 ER PT J AU Mendoza, D Xu, Y Rodriguez-Barradas, M Tweardy, D Orson, F Corry, D AF Mendoza, Daniel Xu, Yi Rodriguez-Barradas, Maria Tweardy, David Orson, Frank Corry, David TI Human dendritic cells induce B-cell responses to polysaccharide antigens SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Mendoza, Daniel; Xu, Yi; Rodriguez-Barradas, Maria; Tweardy, David; Orson, Frank; Corry, David] Baylor Coll Med, Houston, TX 77030 USA. [Mendoza, Daniel; Rodriguez-Barradas, Maria; Orson, Frank; Corry, David] VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1004.2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000027 ER PT J AU Noiret, L Thomas, SR AF Noiret, Lorette Thomas, S. Randall TI Mathematical model of ammonia handling in the rat renal medulla SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Thomas, S. Randall] CNRS, UMR8081, IR4M, F-91405 Orsay, France. [Noiret, Lorette] Harvard Univ, Sch Med, Boston, MA USA. [Noiret, Lorette] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 891.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003222 ER PT J AU Seo, JH Itagaki, K Wang, YY Hagen, S AF Seo, Ji Hye Itagaki, Kiyoshi Wang, Yaoyu Hagen, Susan TI NMDA channel activation regulates Ca2+ permeation and gene transcription during histamine-stimulated gastric acid secretion SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Seo, Ji Hye; Itagaki, Kiyoshi; Hagen, Susan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wang, Yaoyu] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 904.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651003293 ER PT J AU Toba, H Bras, LD Weintraub, S Jin, YF Bradshaw, A Lindsey, M AF Toba, Hiroe Bras, Lisandra de Castro Weintraub, Susan Jin, Yu-Fang Bradshaw, Amy Lindsey, Merry TI Age and SPARC dependent cardiac collagen changes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Lindsey, Merry] GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA. [Bradshaw, Amy] MUSC, Med Gazes Cardiac Res Instit, Charleston, SC USA. [Toba, Hiroe] Kyoto Pharmaceut Univ, Kyoto 607, Japan. [Bradshaw, Amy] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Toba, Hiroe; Bras, Lisandra de Castro; Weintraub, Susan; Jin, Yu-Fang; Lindsey, Merry] San Antonio CV Prote Ctr, San Antonio, TX USA. [Toba, Hiroe; Bras, Lisandra de Castro; Lindsey, Merry] UMMC, Mississippi Ctr Heart Res, Jackson, MS USA. [Weintraub, Susan] UTHSCSA, San Antonio, TX USA. [Jin, Yu-Fang] UTSA, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1120.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651001397 ER PT J AU Wang, H Troy, L Fox, C Meigs, J McKeown, N Jacques, P AF Wang, Huifen Troy, Lisa Fox, Caroline Meigs, James McKeown, Nicola Jacques, Paul TI Longitudinal association of dairy consumption with changes in blood pressure and incident hypertension SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wang, Huifen; McKeown, Nicola; Jacques, Paul] Tufts Univ, USDA, Human Nutr Res Ctr Aging, JM, Boston, MA 02111 USA. [Meigs, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Caroline] NHLBI Framingham Heart Study, Framingham, MA USA. [Troy, Lisa] Univ Massachusetts, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1018.3 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651000113 ER PT J AU White, J Wrann, C Rao, R Wu, ZD Glass, D Spiegelman, B AF White, James Wrann, Christiane Rao, Rajesh Wu, Zhidan Glass, David Spiegelman, Bruce TI G protein coupled receptor 56 is a target gene of the PGC-1 alpha 4 isoform and regulates overload-induced muscle hypertrophy SO FASEB JOURNAL LA English DT Meeting Abstract C1 [White, James; Wrann, Christiane; Rao, Rajesh; Spiegelman, Bruce] Harvard Univ, Sch Med, DFCI, Boston, MA USA. [Wu, Zhidan] Harvard Univ, Sch Med, DFCI, Cambridge, MA 02138 USA. [Glass, David] Novartis Inst BioMed Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 1 SU S MA 1163.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AX0OG UT WOS:000346651002216 ER PT J AU Eve, EJ Koo, S Alshihri, AA Cormier, J Kozhenikov, M Donoff, B Karimbux, NY AF Eve, Elizabeth J. Koo, Samuel Alshihri, Abdulmonem A. Cormier, Jeremy Kozhenikov, Maria Donoff, Bruce Karimbux, Nadeem Y. TI Performance of Dental Students Versus Prosthodontics Residents on a 3D Immersive Haptic Simulator SO JOURNAL OF DENTAL EDUCATION LA English DT Article DE computer simulation; dental caries; dental education; haptics; operative dentistry; preclinical dental training; virtual reality ID TRAINING SIMULATOR AB This study evaluated the performance of dental students versus prosthodontics residents on a simulated caries removal exercise using a newly designed, 3D immersive haptic simulator. The intent of this study was to provide an initial assessment of the simulator's construct validity, which in the context of this experiment was defined as its ability to detect a statistically significant performance difference between novice dental students (n=12) and experienced prosthodontics residents (n=14). Both groups received equivalent calibration training on the simulator and repeated the same caries removal exercise three times. Novice and experienced subjects' average performance differed significantly on the caries removal exercise with respect to the percentage of carious lesion removed and volume of surrounding sound tooth structure removed (p<0.05). Experienced subjects removed a greater portion of the carious lesion, but also a greater volume of the surrounding tooth structure. Efficiency, defined as percentage of carious lesion removed over drilling time, improved significantly over the course of the experiment for both novice and experienced subjects (p<0.001). Within the limitations of this study, experienced subjects removed a greater portion of carious lesion on a 3D immersive haptic simulator. These results are a first step in establishing the validity of this device. C1 [Eve, Elizabeth J.; Donoff, Bruce] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Koo, Samuel] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. [Alshihri, Abdulmonem A.] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat, Cambridge, MA 02138 USA. [Kozhenikov, Maria] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karimbux, Nadeem Y.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. RP Karimbux, NY (reprint author), Tufts Univ, Sch Dent Med, 1 Kneeland St,DHS-1512, Boston, MA 02111 USA. EM Nadeem.Karimbux@tufts.edu FU Office of Naval Research [N00014-10-1-0638] FX This study was supported by the Office of Naval Research, Grant # N00014-10-1-0638. We thank Didhaptic for support in the development of the haptic exercises used in this experimental protocol. Also, we thank Harvard Catalyst Biostatistics for statistical consultation. NR 10 TC 5 Z9 6 U1 2 U2 8 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 APR PY 2014 VL 78 IS 4 BP 630 EP 637 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AY0HX UT WOS:000347279000016 PM 24706694 ER PT J AU Tanpowpong, P Camargo, CA AF Tanpowpong, Pornthep Camargo, Carlos A., Jr. TI Early-life vitamin D deficiency and childhood-onset coeliac disease SO PUBLIC HEALTH NUTRITION LA English DT Article DE Coeliac disease; Vitamin D; Season; Children ID 25-HYDROXYVITAMIN D; INCREASED RISK; BIRTH; AUTOIMMUNITY; INFECTION; CHILDREN; BARRIER; GLIADIN; COHORT; SEASON AB Many studies have investigated the aetiological roles of genetic and environmental factors in coeliac disease (CD) with the long-term goal of developing an effective primary prevention strategy. CD is a condition with dysregulated systemic and intestinal mucosal immune responses to dietary gluten proteins among genetically predisposed individuals. We recently described spring birth as a novel risk factor for CD in children. We believe that the association between season of birth and CD is due to seasonal differences in sunlight exposure and subsequent vitamin D status. Concomitant with global increases in CD prevalence, vitamin D deficiency also is increasingly recognized in children worldwide. Recent studies have shown that vitamin D deficiency can cause improper immune responses, abnormal intestinal mucosal integrity and impaired local defence to pathogenic microbial agents. In conjunction with other potential aetiological factors, we propose a hypothesis model of early-life vitamin D deficiency in the pathogenesis of childhood-onset CD. C1 [Tanpowpong, Pornthep] Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Pediat Gastroenterol,Dept Pediat, Bangkok 10400, Thailand. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Pediat Gastroenterol,Dept Pediat, Bangkok 10400, Thailand. EM ccamargo@mgh.harvard.edu NR 25 TC 5 Z9 5 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD APR PY 2014 VL 17 IS 4 BP 823 EP 826 DI 10.1017/S1368980013003510 PG 4 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA AW6TX UT WOS:000346402200014 PM 24581000 ER PT J AU Merali, HS Morgan, JF Uk, S Phlan, S Wang, LT Korng, S AF Merali, H. S. Morgan, J. F. Uk, S. Phlan, S. Wang, L. T. Korng, S. TI The Lake Clinic - providing primary care to isolated floating villages on the Tonle Sap Lake, Cambodia SO RURAL AND REMOTE HEALTH LA English DT Article DE Cambodia; floating; mobile; Tonle Sap; villages ID RURAL CAMBODIA; WEALTH INEQUALITY; HEALTH; CHILDREN; INFECTION AB Context: One of the most isolated areas in South-East Asia is the Tonle Sap Lake region in Cambodia. Scattered throughout the lake are remote fishing villages that are geographically isolated from the rest of the country. Issue: Receiving health care at a clinic or hospital often involves a full day of travel from the Tonle Sap Lake region, which is unaffordable for the vast majority of residents. Intervention: The Lake Clinic (TLC) is a non-government organization established in 2007. In 2008, a ship was built that was designed for transport of a medical team and supplies to provide primary care to the fishing villages. Initially the project started with one team serving seven villages. TLC has since expanded to two full teams serving 19 villages. TLC provides adult and pediatric primary care, vaccinations, dental services, eyecare services, antenatal care and health education free of charge. From 2008 to 2012, there were a total of 13 160 pediatric visits and 17 722 adult visits. In addition to these services, 739 patients received dental care, 346 patients received eye care, there were 1239 antenatal visits, 116 family planning visits, and 1600 patients received health education. In total, 130 patients were referred to hospitals or health centers for a higher level of care. A total of 6627 immunizations were provided. The most common pediatric illness was upper respiratory infection (44.4%), and the most common adult illness observed was gastritis (20.6%). Lessons learned: Despite the challenges, TLC has been able to achieve a significant goal: to provide primary care medical services to a remote area of Cambodia where no medical services were previously available. TLC strives to strengthen healthcare delivery with the goal to provide the best possible care in the region. New partnerships have allowed laboratory capacity and a formalized hospital referral system for pediatric patients beginning in 2014. A new boat, which completed construction in December 2013 and is now fully operational, has allowed the TLC team to reach a greater number of patients more efficiently. C1 [Merali, H. S.] Hosp Sick Children, Div Paediat Emergency Med, Toronto, ON M5G 1X8, Canada. [Morgan, J. F.; Uk, S.; Phlan, S.; Korng, S.] Lake Clin Cambodia, Siem Reap, Cambodia. [Wang, L. T.] MassGen Hosp Children, Div Global Hlth, Pediat Emergency Med Serv, Boston, MA USA. RP Merali, HS (reprint author), Hosp Sick Children, Div Paediat Emergency Med, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. NR 23 TC 1 Z9 1 U1 2 U2 14 PU AUSTRALIAN RURAL HEALTH EDUC NETWORK PI DEAKIN WEST PA PO BOX 242, DEAKIN WEST, ACT 2600, AUSTRALIA SN 1445-6354 J9 RURAL REMOTE HEALTH JI Rural Remote Health PD APR-JUN PY 2014 VL 14 IS 2 AR 2612 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AR3WY UT WOS:000343520900012 PM 24811837 ER PT J AU Bakaeen, FG Chu, D Kelly, RF Holman, WL Jessen, ME Ward, HB AF Bakaeen, Faisal G. Chu, Danny Kelly, Rosemary F. Holman, William L. Jessen, Michael E. Ward, Herbert B. TI Perioperative Outcomes after On-and Off-Pump Coronary Artery Bypass Grafting SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE Cardiac surgical procedures/adverse effects/methods/mortality; coronary artery bypass/adverse effects/methods/mortality; morbidity; mortality; outcome assessment ID REDUCE MORBIDITY; RANDOMIZED-TRIAL; SURGERY; MORTALITY; REVASCULARIZATION; STROKE; METAANALYSIS; SURVIVAL; PATENCY; IMPROVEMENT AB Although numerous reports describe the results of off-pump coronary artery bypass grafting (CABG) at specialized centers and in select patient populations, it remains unclear how off-pump CABG affects real-world patient outcomes. We conducted a large, multicenter observational cohort study of perioperative death and morbidity in on-pump (ON) versus off-pump (OFF) CABG. We reviewed Veterans Affairs Surgical Quality Improvement Program data for all patients (N=65,097) who underwent isolated CABG from October 1997 through April 2011 (intention-to-treat data were available from 2005 onward). The primary outcome was perioperative (30-day or in-hospital) death; the secondary outcomes were perioperative stroke, dialysis dependence, reoperation for bleeding, mechanical circulatory support, myocardial infarction, ventilator support >= 48 hr, and mediastinitis. Propensity scores calculated from age, 17 preoperative risk factors, and year of surgery were used to match 8,911 OFF with 26,733 ON patients. In the complete cohort, compared with the ON patients (n=53,468), the OFF patients (n=11,629) had less perioperative death (2.02% vs 2.53%, P=0.0012) and lower incidences of all morbidities except perioperative myocardial infarction. In the matched cohort, perioperative death did not differ significantly between OFF and ON patients (1.94% vs 2.28%, P=0.06), but the OFF group had lower incidences of all morbidities except for perioperative myocardial infarction and mediastinitis. A subgroup intention-to-treat analysis yielded similar but smaller outcome differences between the ON and OFF groups. Off-pump CABG might be associated with decreased operative morbidity but did not affect operative death, compared with on-pump CABG. Future studies should examine the effect of off-pump CABG on long-term outcomes. C1 [Bakaeen, Faisal G.; Chu, Danny] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Bakaeen, Faisal G.; Chu, Danny] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX 77030 USA. [Kelly, Rosemary F.; Ward, Herbert B.] Univ Minnesota, Minneapolis VAMC, Div Cardiothorac Surg, Minneapolis, MN 55417 USA. [Holman, William L.] Univ Alabama Birmingham, Dept Cardiothorac Surg, Birmingham, AL 35233 USA. Birmingham VAMC, Birmingham, AL 35233 USA. [Jessen, Michael E.] Univ Texas SW Med Ctr Dallas, Div Cardiothorac Surg, Dallas, TX 75390 USA. RP Bakaeen, FG (reprint author), Michael E DeBakey VA Med Ctr, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu FU VA Health Services Research and Development Grant [IHY 99214-1]; Office of Research at the Northport and Eastern Colorado Health Care System Denver Veterans Affairs Medical Centers; Office of Development at the Northport and Eastern Colorado Health Care System Denver Veterans Affairs Medical Centers FX The CICSP-X study was initially funded by VA Health Services Research and Development Grant #IHY 99214-1 (Dr. Shroyer, Principal Investigator), with ongoing support from the Office of Patient Care Services, VA Central Office, Washington, DC. This project was supported in part by the Offices of Research and Development at the Northport and Eastern Colorado Health Care System Denver Veterans Affairs Medical Centers. NR 32 TC 5 Z9 6 U1 0 U2 2 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 EI 1526-6702 J9 TEX HEART I J JI Tex. Heart Inst. J. PD APR PY 2014 VL 41 IS 2 BP 144 EP 151 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AQ1MN UT WOS:000342545600012 PM 24808773 ER PT J AU Zhu, ED Louis, L Brooks, DJ Bouxsein, ML Demay, MB AF Zhu, Eric D. Louis, Leeann Brooks, Daniel J. Bouxsein, Mary L. Demay, Marie B. TI Effect of Bisphosphonates on the Rapidly Growing Male Murine Skeleton SO ENDOCRINOLOGY LA English DT Article ID BONE-MINERAL DENSITY; IMPERFECTA TYPE-I; OSTEOGENESIS IMPERFECTA; POSTMENOPAUSAL OSTEOPOROSIS; HYPERTROPHIC CHONDROCYTES; INTRAVENOUS PAMIDRONATE; SECONDARY OSTEOPOROSIS; ALENDRONATE TREATMENT; CONTROLLED-TRIAL; ZOLEDRONIC ACID AB Bisphosphonates are effective for preventing and treating skeletal disorders associated with hyperresorption. Their safety and efficacy has been studied in adults where the growth plate is fused and there is no longitudinal bone growth and little appositional growth. Although bisphosphonate use in the pediatric population was pioneered for compassionate use in the treatment of osteogenesis imperfecta, they are being increasingly used for the treatment and prevention of bone loss in children at risk of hyperresorptive bone loss. However, the effect of these agents on the growing skeleton in disorders other than osteogenesis imperfecta has not been systematically compared. Studies were, therefore, undertaken to examine the consequences of bisphosphonate administration on the growth plate and skeletal microarchitecture during a period of rapid growth. C57Bl6/J male mice were treated from 18 to 38 days of age with vehicle, alendronate, pamidronate, zoledronate, or clodronate at doses selected to replicate those used in humans. Treatment with alendronate, pamidronate, and zoledronate, but not clodronate, led to a decrease in the number of chondrocytes per column in the hypertrophic chondrocyte layer. This was not associated with altered hypertrophic chondrocyte apoptosis or vascular invasion at the growth plate. The effects of pamidronate on trabecular microarchitecture were less beneficial than those of alendronate and zoledronate. Pamidronate did not increase cortical thickness or cortical area/total area relative to control mice. These studies suggest that bisphosphonate administration does not adversely affect skeletal growth. Long-term investigations are required to determine whether the differences observed among the agents examined impact biomechanical integrity of the growing skeleton. C1 [Demay, Marie B.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 11,50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01AR061376] FX This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR061376 (to M.B.D.). NR 39 TC 7 Z9 7 U1 1 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2014 VL 155 IS 4 BP 1188 EP 1196 DI 10.1210/en.2013-1993 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PW UT WOS:000342342000005 PM 24422540 ER PT J AU Abu Shehab, M Damerill, I Shen, T Rosario, FJ Nijland, M Nathanielsz, PW Kamat, A Jansson, T Gupta, MB AF Abu Shehab, Majida Damerill, Ian Shen, Tong Rosario, Fredrick J. Nijland, Mark Nathanielsz, Peter W. Kamat, Amrita Jansson, Thomas Gupta, Madhulika B. TI Liver mTOR Controls IGF-I Bioavailability by Regulation of Protein Kinase CK2 and IGFBP-1 Phosphorylation in Fetal Growth Restriction SO ENDOCRINOLOGY LA English DT Article ID FACTOR-BINDING PROTEIN-1; AMINO-ACID-CONCENTRATIONS; MAMMALIAN TARGET; INTRAUTERINE GROWTH; GENE-EXPRESSION; INSULIN REGULATION; TROPHOBLAST CELLS; CASEIN KINASE-2; HUMAN FETUS; RAPAMYCIN AB Fetal growth restriction (FGR) increases the risk for perinatal complications and predisposes the infant to diabetes and cardiovascular disease later in life. No treatment for FGR is available, and the underlying pathophysiology remains poorly understood. Increased IGFBP-1 phosphorylation has been implicated as an important mechanism by which fetal growth is reduced. However, to what extent circulating IGFBP-1 is phosphorylated in FGR is unknown, and the molecular mechanisms linking FGR to IGFBP-1 phosphorylation have not been established. We used umbilical cord plasma of appropriate for gestational age (AGA) and growth-restricted human fetuses and determined IGFBP-1 and IGF-I concentrations (ELISA) and site-specific IGFBP-1 phosphorylation (Western blotting using IGFBP-1 phospho-site specific antibodies). In addition, we used a baboon model of FGR produced by 30% maternal nutrient restriction and determined mammalian target of rapamycin (mTOR) C1 activity, CK2 expression/activity, IGFBP-1 expression and phosphorylation, and IGF-I levels in baboon fetal liver by Western blot, enzymatic assay, and ELISA. HepG2 cells and primary fetal baboon hepatocytes were used to explore mechanistic links between mTORC1 signaling and IGFBP-1 phosphorylation. IGFBP-1 was hyperphosphorylated at Ser101, Ser119, and Ser169 in umbilical plasma of human FGR fetuses. IGFBP-1 was also hyperphosphorylated at Ser101, Ser119, and Ser169 in the liver of growth-restricted baboon fetus. mTOR signaling was markedly inhibited, whereas expression and activity of CK2 was increased in growth-restricted baboon fetal liver in vivo. Using HepG2 cells and primary fetal baboon hepatocytes, we established a mechanistic link between mTOR inhibition, CK2 activation, IGFBP-1 hyperphosphorylation, and decreased IGF-I-induced IGF-I receptor autophosphorylation. We provide clear evidence for IGFBP-1 hyperphosphorylation in FGR and identified an mTOR and CK2-mediated mechanism for regulation of IGF-I bioavailability. Our findings are consistent with the model that inhibition of mTOR in the fetal liver, resulting in increased CK2 activity and IGFBP-1 hyperphosphorylation, constitutes a novel mechanistic link between nutrient deprivation and restricted fetal growth. C1 [Abu Shehab, Majida; Gupta, Madhulika B.] Univ Western Ontario, Dept Pediat, London, ON N6C 2V5, Canada. [Damerill, Ian; Shen, Tong; Gupta, Madhulika B.] Univ Western Ontario, Dept Biochem, London, ON N6C 2V5, Canada. [Gupta, Madhulika B.] Univ Western Ontario, Childrens Hlth Res Inst, London, ON N6C 2V5, Canada. [Rosario, Fredrick J.; Nijland, Mark; Nathanielsz, Peter W.; Jansson, Thomas] Univ Texas Hlth Sci Ctr San Antonio, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA. [Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Kamat, Amrita] South Texas Vet Hlth Care Syst, Geriatr Res Educ Ctr, San Antonio, TX 78229 USA. [Kamat, Amrita] South Texas Vet Hlth Care Syst, Ctr Clin, San Antonio, TX 78229 USA. RP Gupta, MB (reprint author), Univ Western Ontario, Childrens Hlth Res Inst, Dept Pediat, VRL Room A5-136 WC,800 Commissioners Rd East, London, ON N6C 2V5, Canada. EM mbgupta@uwo.ca OI Nathanielsz, Peter/0000-0001-8410-6280 FU Lawson Health Research Institute and Children's Health Research Institute; National Institutes of Health [HD 078313, HD 21350]; VA (Merit Review Award) [1I01BX001744-01A1] FX This work was supported by the Lawson Health Research Institute and Children's Health Research Institute (grants to M.B.G.), National Institutes of Health (Grants HD 078313 to M.B.G. and T.J. and HD 21350 to P.W.N.), and the VA (Merit Review Award 1I01BX001744-01A1 to A.K.). NR 38 TC 6 Z9 6 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2014 VL 155 IS 4 BP 1327 EP 1339 DI 10.1210/en.2013-1759 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PW UT WOS:000342342000017 PM 24437487 ER PT J AU Fazeli, PK Wang, IS Miller, KK Herzog, DB Misra, M Lee, H Finkelstein, JS Bouxsein, ML Klibanski, A AF Fazeli, Pouneh K. Wang, Irene S. Miller, Karen K. Herzog, David B. Misra, Madhusmita Lee, Hang Finkelstein, Joel S. Bouxsein, Mary L. Klibanski, Anne TI Teriparatide Increases Bone Formation and Bone Mineral Density in Adult Women With Anorexia Nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; PARATHYROID-HORMONE; YOUNG-WOMEN; ADOLESCENT GIRLS; LATE-ONSET; RAT BONE; TURNOVER; DEHYDROEPIANDROSTERONE; OSTEOPOROSIS; METABOLISM AB Context: Anorexia nervosa (AN), a prevalent psychiatric disorder predominantly affecting women, is characterized by self-induced starvation and low body weight. Increased clinical fractures are common, and most women have low bone mineral density (BMD). Previously investigated treatments have led to no or modest increases in BMD in AN. Objective: Our objective was to investigate the effect of teriparatide (TPT; human PTH[1-34]), an anabolic agent, on low bone mass in women with AN. Design, Setting, and Patients: This randomized, placebo-controlled trial at a clinical research center included 21 women with AN: 10 (mean age +/- SEM, 47 +/- 2.7 years) treated with TPT and 11 (47.1 +/- 2.3 years) treated with placebo. Interventions: TPT (20 mu g SC) or placebo was administered for 6 months. Main Outcome Measures: Our primary outcome measure was change in BMD of the spine and hip by dual-energy x-ray absorptiometry. Secondary outcome measures included changes inserum N-terminal propeptide of type 1 procollagen (P1NP), C-terminal collagen cross-links, sclerostin, and IGF-1 levels. Results: At 6 months, spine BMD increased significantly more with TPT (posteroanterior spine, 6.0% +/- 1.4%; lateral spine, 10.5% +/- 2.5%) compared with placebo (posteroanterior spine, 0.2% +/- 0.7%, P < .01; lateral spine, -0.6% +/- 1.0%; P < .01). The results remained significant after controlling for baseline body mass index, P1NP, and IGF-1. Changes in femoral neck (P = .4) and total hip (P = 0.8) BMD were comparable in both groups, as were changes in weight. Serum P1NP levels increased after 3 months of TPT treatment and remained at this higher level at 6 months, whereas P1NP levels were unchanged in the placebo group (P = .02). TPT was well-tolerated by all subjects. Conclusions: This study demonstrates that TPT administration increases spine BMD substantially after only 6 months of therapy in women with AN. C1 [Fazeli, Pouneh K.; Wang, Irene S.; Miller, Karen K.; Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Fazeli, Pouneh K.; Miller, Karen K.; Herzog, David B.; Misra, Madhusmita; Lee, Hang; Finkelstein, Joel S.; Bouxsein, Mary L.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fazeli, PK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM pkfazeli@partners.org FU National Institutes of Health (NIH) [K23-DK094820]; NIH/National Center for Research Resources [UL1 RR025758]; NIH/National Center for Advancing Translational Science [UL1 TR000170-05]; Jane Walentas Women's Health Award from the Foundation for Women's Wellness FX The project described was supported by National Institutes of Health (NIH) Grant K23-DK094820 (Fazeli); the NIH/National Center for Research Resources Grant UL1 RR025758 (to the Harvard Clinical and Translational Science Center); NIH/National Center for Advancing Translational Science Grant UL1 TR000170-05 (to the Harvard Clinical and Translational Science Center); and the Jane Walentas Women's Health Award from the Foundation for Women's Wellness. NR 36 TC 14 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2014 VL 99 IS 4 BP 1322 EP 1329 DI 10.1210/jc.2013-4105 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP7UU UT WOS:000342283500055 PM 24456286 ER PT J AU Bertagna, X Pivonello, R Fleseriu, M Zhang, YM Robinson, P Taylor, A Watson, CE Maldonado, M Hamrahian, AH Boscaro, M Biller, BMK AF Bertagna, Xavier Pivonello, Rosario Fleseriu, Maria Zhang, Yiming Robinson, Paul Taylor, Ann Watson, Catherine E. Maldonado, Mario Hamrahian, Amir H. Boscaro, Marco Biller, Beverly M. K. TI LCI699, a Potent 11 beta-hydroxylase Inhibitor, Normalizes Urinary Cortisol in Patients With Cushing's Disease: Results From a Multicenter, Proof-of-Concept Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MANAGEMENT; KETOCONAZOLE; METYRAPONE; PITUITARY; MITOTANE AB Introduction: The clinical features and increased mortality associated with Cushing's syndrome result from a chronic excess of circulating cortisol. As LCI699 potently inhibits 11 beta-hydroxylase, which catalyzes the final step of cortisol synthesis, it is a potential new treatment for Cushing's disease, the most common cause of endogenous Cushing's syndrome. Methods: Adult patients with moderate-to-severe Cushing's disease (urinary free cortisol [UFC] levels > 1.5 x ULN [upper limit of normal]) received oral LCI699 for 10 weeks in this proof-of-concept study. LCI699 was initiated at 4 mg/d in two equal doses; the dose was escalated every 14 days to 10, 20, 40, and 100 mg/d until UFC normalized, whereupon the dose was maintained until treatment ended (day 70). The primary endpoint was UFC <= ULN or a >= 50% decrease from baseline at day 70. Results: Twelve patients were enrolled and completed the study. Baseline UFC ranged over 1.6-17.0 x ULN. All 12 patients achieved UFC <= ULN or a >= 50% decrease from baseline at day 70; 11 (92%) had normal UFC levels at that time. After treatment discontinuation (day 84), UFC was > ULN in 10 patients with available measurements. Mean 11-deoxycortisol, 11-deoxycorticosterone, and adrenocorticotropic hormone levels increased during treatment and declined after discontinuation. Mean systolic and diastolic blood pressure decreased from baseline by 10.0 and 6.0 mmHg, respectively. LCI699 was generally well tolerated; most adverse events (AEs) were mild or moderate. The most common AEs included fatigue (7/12), nausea (5/12), and headache (3/12). No serious drug-related AEs were reported. Conclusions: LCI699 was efficacious and well tolerated in patients with Cushing's disease enrolled in this proof-of-concept study. C1 [Bertagna, Xavier] Univ Paris 05, Fac Med Paris Descartes, Hop Cochin, Ctr Reference Malad Rares Surrenale, F-75014 Paris, France. [Pivonello, Rosario] Univ Naples Federico II, Dipartimento Med Clin Chirurgia, IT-80131 Naples, Italy. [Fleseriu, Maria] Oregon Hlth & Sci Univ, Northwest Pituitary Ctr, Dept Med & Neurol Surg, Portland, OR 97239 USA. [Zhang, Yiming] Nova Pharmaceut Corp, E Hanover, NJ 07936 USA. [Robinson, Paul] Novartis Pharmaceut UK Ltd, Horsham RH12 5AB, W Sussex, England. [Taylor, Ann; Watson, Catherine E.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA. [Maldonado, Mario] Oncol Business Unit, Clin Dev, CH-4002 Basel, Switzerland. [Hamrahian, Amir H.] Cleveland Clin Fdn, Dept Endocrinol Diabet & Metab, Cleveland, OH 44106 USA. [Boscaro, Marco] Polytech Univ Marche, Div Endocrinol, I-60121 Ancona, Italy. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. RP Bertagna, X (reprint author), Hop Cochin, Dept Endocrinol, 27 Rue Faubourg St Jacques, F-75014 Paris, France. EM xavier.bertagna@cch.aphp.fr OI BOSCARO, MARCO/0000-0003-2596-1652 FU Novartis Pharma AG; Novartis Pharmaceuticals Corporation FX We thank Andrew Jones, PhD for medical editorial assistance with this manuscript. This study was funded by Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. NR 24 TC 57 Z9 58 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2014 VL 99 IS 4 BP 1375 EP 1383 DI 10.1210/jc.2013-2117 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP7UU UT WOS:000342283500061 PM 24423285 ER PT J AU Shaw, ND Srouji, SS Welt, CK Cox, KH Fox, JH Adams, JM Sluss, PM Hall, JE AF Shaw, N. D. Srouji, S. S. Welt, C. K. Cox, K. H. Fox, J. H. Adams, J. M. Sluss, P. M. Hall, J. E. TI Evidence That Increased Ovarian Aromatase Activity and Expression Account for Higher Estradiol Levels in African American Compared With Caucasian Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; GRANULOSA-CELL DIFFERENTIATION; REPRODUCTIVE-AGE WOMEN; INHIBIN-B; CULTURED GRANULOSA; POLYCYSTIC OVARIES; UTERINE LEIOMYOMA; GENE-EXPRESSION; BODY-SIZE AB Context: Serum estradiol levels are significantly higher across the menstrual cycle in African American (AAW) compared with Caucasian women (CW) in the presence of similar FSH levels, yet the mechanism underlying this disparity is unknown. Objective: The objective of the study was to determine whether higher estradiol levels in AAW are due to increased granulosa cell aromatase mRNA expression and activity. Design: The design of the study included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. Subjects: Healthy, normal cycling AAW (n = 15) and CW (n = 14) aged 19-34 years participated in the study. Main Outcome Measures: Hormone levels in peripheral blood and follicular fluid (FF) aspirates and aromatase and FSH receptor mRNA expression in granulosa cells were measured. Results: AAW had higher FF estradiol [1713.0 (1144.5-2032.5) vs 994.5 (647.3-1426.5) ng/mL; median (interquartile range); P < .001] and estrone [76.9 (36.6 -173.4) vs 28.8 (22.5-42.1) ng/mL; P < .001] levels than CW, independent of follicle size. AAW also had lower FF androstenedione to estrone (7 +/- 1.8 vs 15.8 +/- 4.1; mean +/- SE; P = .04) and T to estradiol (0.01 +/- 0.002 vs 0.02 +/- 0.005; P = .03) ratios, indicating enhanced ovarian aromatase activity. There was a 5-fold increase in granulosa cell aromatase mRNA expression in AAW compared with CW (P < .001) with no difference in expression of FSH receptor. FSH, inhibin A, inhibin B, and AMH levels were not different in AAW and CW. Conclusions: Increased ovarian aromatase mRNA expression, higher FF estradiol levels, and decreased FF androgen to estrogen ratios in AAW compared with CW provide compelling evidence that racial differences in ovarian aromatase activity contribute to higher levels of estradiol in AAW across the menstrual cycle. The absence of differences in FSH, FSH receptor expression, and AMH suggest that population-specific genetic variation in CYP19, the gene encoding aromatase, or in factors affecting its expression should be sought. C1 [Shaw, N. D.; Srouji, S. S.; Welt, C. K.; Cox, K. H.; Adams, J. M.; Sluss, P. M.; Hall, J. E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Shaw, N. D.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Srouji, S. S.; Fox, J. H.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Infertil & Reprod Surg, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org RI Cox, Kimberly/P-1931-2016; OI Cox, Kimberly/0000-0002-7097-9563; Welt, Corrine/0000-0002-8219-5504; Shaw, Natalie/0000-0002-0847-9170; Hall, Janet/0000-0003-4644-3061 FU National Institutes of Health [R01HD 42708, M01 RR01066, 1K23 HD073304-01]; Harvard Catalyst and the Harvard Clinical and Translational Science Center (National Center for Research Resources) [8UL1TR000170-05]; Harvard Catalyst and the Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award) [8UL1TR000170-05]; Harvard Catalyst and the Harvard Clinical and Translational Science Center (Harvard University) FX This work was supported by National Institutes of Health Grants R01HD 42708 and M01 RR01066. N.D.S. received support from the National Institutes of Health Grant 1K23 HD073304-01). This work was also supported by the Harvard Catalyst and 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 54 TC 6 Z9 6 U1 0 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2014 VL 99 IS 4 BP 1384 EP 1392 DI 10.1210/jc.2013-2398 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP7UU UT WOS:000342283500062 PM 24285681 ER PT J AU Wewalka, M Patti, ME Barbato, C Houten, SM Goldfine, AB AF Wewalka, Marlene Patti, Mary-Elizabeth Barbato, Corinne Houten, Sander M. Goldfine, Allison B. TI Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE-HOMEOSTASIS; METABOLISM; HUMANS; MICE; MELLITUS; MODEL; CHOLESTEROL; SENSITIVITY; RESISTANCE; CHALLENGE AB Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired-compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A(1c) (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = -0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. C1 [Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wewalka, Marlene; Patti, Mary-Elizabeth; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Houten, Sander M.] Univ Amsterdam, Acad Med Ctr, Lab Genet Metab Dis, Dept Clin Chem, NL-1105 AZ Amsterdam, Netherlands. [Houten, Sander M.] Univ Amsterdam, Acad Med Ctr, Lab Genet Metab Dis, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM marlene.wewalka@meduniwien.ac.at; sander.houten@mssm.edu; allison.goldfine@joslin.harvard.edu OI Houten, Sander/0000-0002-6167-9147 FU National Institutes of Health [DK062948]; Juvenile Diabetes Research Foundation; Marietta Blau Grant [ICM-2010-02797]; Daiichi Sankyo; [DK036836]; [DK060837]; [R56DK095451] FX This work was supported by National Institutes of Health Grant DK062948 (to M.-E.P.); Grants DK036836 and DK060837 (to M.-E.P. and A.B.G.); and Grant R56DK095451 (to A.B.G. and M.W.); the Juvenile Diabetes Research Foundation (to M.-E.P. and A.B.G.); Marietta Blau Grant ICM-2010-02797 (to M.W.); an Investigator Initiated Study Grant from Daiichi Sankyo; and support for the Joslin Clinical Research Center from its philanthropic donors. NR 39 TC 14 Z9 14 U1 1 U2 15 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2014 VL 99 IS 4 BP 1442 EP 1451 DI 10.1210/jc.2013-3367 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP7UU UT WOS:000342283500069 PM 24432996 ER PT J AU Salian-Mehta, S Xu, M Knox, AJ Plummer, L Slavov, D Taylor, M Bevers, S Hodges, RS Crowley, WF Wierman, ME AF Salian-Mehta, S. Xu, M. Knox, A. J. Plummer, L. Slavov, D. Taylor, M. Bevers, S. Hodges, R. S. Crowley, W. F., Jr. Wierman, M. E. TI Functional Consequences of AXL Sequence Variants in Hypogonadotropic Hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; RECEPTOR TYROSINE KINASE; KALLMANN-SYNDROME; NEURONAL MIGRATION; LUTEINIZING-HORMONE; GENE-EXPRESSION; PROTEIN-KINASE; SURVIVAL; IDENTIFICATION; ACTIVATION AB Context: Prior studies showed that Axl /Tyro3 null mice have delayed first estrus and abnormal cyclicity due to developmental defects in GnRH neuron migration and survival. Objective: The objective of the study was to test whether the absence of Axl would alter reproductive function in mice and that mutations in AXL are present in patients with Kallmann syndrome (KS) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Design and Setting: The sexual maturation of Axl null mice was examined. The coding region of AXL was sequenced in 104 unrelated, carefully phenotyped KS or nIHH subjects. Frequency of mutations was compared with other causes of GnRH deficiency. Functional assays were performed on the detected mutations. Results: Axl null mice demonstrated delay in first estrus and the interval between vaginal opening and first estrus. Three missense AXL mutations (p.L50F, p.S202C, and p.Q361P) and one intronic variant 6 bp upstream from the start of exon 5 (c.586-6 C>T) were identified in two KS and 2 two nIHH subjects. Comparison of the frequencies of AXL mutations with other putative causes of idiopathic hypogonadotropic hypogonadism confirmed they are rare variants. Testing of the c.586-6 C>T mutation revealed no abnormal splicing. Surface plasmon resonance analysis of the p.L50F, p.S202C, and p.Q361P mutations showed no altered Gas6 ligand binding. In contrast, GT1-7 GnRH neuronal cells expressing p.S202C or p.Q361P demonstrated defective ligand dependent receptor processing and importantly aberrant neuronal migration. In addition, the p.Q361P showed defective ligand independent chemotaxis. Conclusions: Functional consequences of AXL sequence variants in patients with idiopathic hypogonadotropic hypogonadism support the importance of AXL and the Tyro3, Axl, Mer (TAM) family in reproductive development. C1 [Salian-Mehta, S.; Xu, M.; Knox, A. J.; Wierman, M. E.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA. [Slavov, D.; Taylor, M.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO 80045 USA. [Bevers, S.; Hodges, R. S.] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA. [Wierman, M. E.] Vet Affairs Med Ctr, Vet Affairs Res Serv, Denver, CO 80220 USA. [Plummer, L.; Crowley, W. F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Plummer, L.; Crowley, W. F., Jr.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Wierman, ME (reprint author), Univ Colorado, Sch Med, 12801 East 17th Ave,RC1 South,MS8106, Aurora, CO 80045 USA. EM margaret.wierman@ucdenver.edu FU National Institute of Health [HD31191, U54 HD28138]; NHLBI Gene Ontology Exome Sequencing Project; Lung Gene Ontology Sequencing Project [HL-102923]; Women's Health Initiative Sequencing Project [HL-102924]; Broad Gene Ontology Sequencing Project [HL-102925]; Seattle Gene Ontology Sequencing Project [HL-102926]; Heart Gene Ontology Sequencing Project [HL-103010] FX We thank Angela Pierce and Brian Bliesner for their efforts to characterize the reproductive phenotype of AXL null mice. Surface Plasmon Resonance experiments were conducted in the Biophysics Core Facility at the University of Colorado School of Medicine. We thank Margaret Au (Massachusetts General Hospital) for her help in the initial mutant screening and Nelly Pitteloud (Centre Hospitalier Universitaire Vaudois) for her valuable inputs during the preparation of this manuscript. We acknowledge the NHLBI Gene Ontology Exome Sequencing Project, the Lung Gene Ontology Sequencing Project (HL-102923), the Women's Health Initiative Sequencing Project (HL-102924), the Broad Gene Ontology Sequencing Project (HL-102925), the Seattle Gene Ontology Sequencing Project (HL-102926), and the Heart Gene Ontology Sequencing Project (HL-103010).; This work was supported by National Institute of Health Grant HD31191 (to M.E.W.) and Grant U54 HD28138 (to W.F.C.). NR 40 TC 2 Z9 2 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2014 VL 99 IS 4 BP 1452 EP 1460 DI 10.1210/jc.2013-3426 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP7UU UT WOS:000342283500070 PM 24476074 ER PT J AU Amrein, K Quraishi, SA Litonjua, AA Gibbons, FK Pieber, TR Camargo, CA Giovannucci, E Christopher, KB AF Amrein, Karin Quraishi, Sadeq A. Litonjua, Augusto A. Gibbons, Fiona K. Pieber, Thomas R. Camargo, Carlos A., Jr. Giovannucci, Edward Christopher, Kenneth B. TI Evidence for a U-Shaped Relationship Between Prehospital Vitamin D Status and Mortality: A Cohort Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM 25-HYDROXYVITAMIN D; ALL-CAUSE MORTALITY; LOCALLY WEIGHTED REGRESSION; D DEFICIENCY; D SUPPLEMENTATION; CONTROLLED-TRIAL; CRITICAL-CARE; D TOXICITY; RISK; COMMUNITY AB Objective: The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D] and the risk of mortality after hospital admission. Design: We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011. Setting: The study was conducted at two Boston teaching hospitals. Patients: A total of 24 094 adult inpatients participated in the study. Intervention: There was no intervention. Measurements: All patients had serum 25(OH) D measured before hospitalization. The exposure of interest was 25(OH) D categorized as less than 10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 30-49.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and 70 ng/mL or greater. The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders. Results: After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH) D draw, and the Deyo-Charlson index, patients with 25(OH) D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30-49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D < 10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and >= 70 ng/mL was 2.01 (1.68-2.40), 1.89 (1.64-2.18), 1.34 (1.16-1.56), 0.94 (0.69-1.26), 1.52 (1.03-2.25), and 1.69 (1.09-2.61), respectively, compared with patients with 25(OH)D levels 30-49.9 ng/mL]. Limitations: A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study. Conclusions: Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients. C1 [Amrein, Karin; Pieber, Thomas R.] Med Univ Graz, Dept Internal Med, Div Endocrinol & Metab, A-8036 Graz, Austria. [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, Nathan E Hellman Mem Lab, 75 Francis St,MRB 418, Boston, MA 02115 USA. EM kbchristopher@partners.org FU National Institutes of Health [5T32GM007592-33, UL1 RR025758, R01 AI093723, U01 AI087881, K08AI060881] FX S.A.Q. received support from the National Institutes of Health Grants 5T32GM007592-33 and UL1 RR025758. C.A.C. received support from National Institutes of Health Grants R01 AI093723 and U01 AI087881. K.B.C. received support from National Institutes of Health Grant K08AI060881. NR 57 TC 33 Z9 36 U1 1 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2014 VL 99 IS 4 BP 1461 EP 1469 DI 10.1210/jc.2013-3481 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP7UU UT WOS:000342283500071 PM 24423347 ER PT J AU Brahmer, JR Horn, L Antonia, SJ Spigel, DR Sequist, LV Ahlers, CM Sankar, V Kollia, G Gettinger, S AF Brahmer, J. R. Horn, L. Antonia, S. J. Spigel, D. R. Sequist, L. V. Ahlers, C. M. Sankar, V. Kollia, G. Gettinger, S. TI CLINICAL ACTIVITY, SAFETY AND SUBPOPULATION RESPONSE ANALYSIS OF NIVOLUMAB (ANTI-PD-1; BMS-936558; ONO-4538) IN PATIENTS (PT) WITH NON-SMALL CELL LUNG CANCER (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Brahmer, J. R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Horn, L.] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. [Antonia, S. J.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Interdisciplinary Oncol, Tampa, FL 33682 USA. [Antonia, S. J.] Univ S Florida, H Lee Moffitt Canc Ctr, Program Immunol, Tampa, FL 33682 USA. [Antonia, S. J.] Res Inst, Tampa, FL USA. [Spigel, D. R.] Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. [Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ahlers, C. M.; Sankar, V.; Kollia, G.] Bristol Myers Squibb Co, Princeton, NJ USA. [Gettinger, S.] Yale Canc Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 6 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 APR PY 2014 VL 9 IS 4 SU 1 MA 96PD BP S39 EP S39 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AO9PS UT WOS:000341688500096 ER PT J AU Wakelee, H Soria, J Camidge, R Gadgeel, S Goldman, J Varga, A Solomon, B Papadimitrakopoulou, V Kaur, P Sequist, LV AF Wakelee, H. Soria, J. Camidge, R. Gadgeel, S. Goldman, J. Varga, A. Solomon, B. Papadimitrakopoulou, V. Kaur, P. Sequist, L. V. TI FIRST-IN-HUMAN EVALUATION OF CO-1686, AN IRREVERSIBLE, HIGHLY SELECTIVE TYROSINE KINASE INHIBITOR OF MUTATIONS OF EGFR (ACTIVATING AND T790M) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Wakelee, H.] Stanford Univ, Stanford, CA 94305 USA. [Soria, J.; Varga, A.] Inst Gustave Roussy, Villejuif, France. [Camidge, R.] Univ Colorado, Denver, CO 80202 USA. [Gadgeel, S.] Karmanos Canc Inst, Detroit, MI USA. [Goldman, J.] Univ Calif Los Angeles, Santa Monica, CA USA. [Solomon, B.] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kaur, P.] Clovis Oncol, Clin, Boulder, CO USA. [Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 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 APR PY 2014 VL 9 IS 4 SU 1 MA 93O BP S38 EP S38 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AO9PS UT WOS:000341688500093 ER PT J AU Anderson, T Donohue, JM Morden, NE Zhao, XH Mor, M Thorpe, C Good, C Fine, MJ Gellad, WF AF Anderson, Timothy Donohue, Julie M. Morden, Nancy E. Zhao, Xinhua Mor, Maria Thorpe, Carolyn Good, Chester Fine, Michael J. Gellad, Walid F. TI REGIONAL CORRELATION IN BRAND-NAME PRESCRIPTION DRUG USE AMONG VA AND MEDICARE PART D PATIENTS WITH DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Anderson, Timothy] UPMC, Pittsburgh, PA USA. [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Morden, Nancy E.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Zhao, Xinhua; Mor, Maria; Thorpe, Carolyn; Good, Chester; Fine, Michael J.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Carolyn] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Good, Chester; Fine, Michael J.; Gellad, Walid F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S196 EP S197 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201096 ER PT J AU Ando, N Taki, N Kumabe, A Nishimura, Y Kudo, M Kenzaka, T Dhaliwal, G Matsumura, M AF Ando, Naokatsu Taki, Naoya Kumabe, Ayako Nishimura, Yoshioki Kudo, Michiko Kenzaka, Tsuneaki Dhaliwal, Gurpreet Matsumura, Masami TI PSEUDORENAL FAILURE CAUSED BY SPONTANEOUS RUPTURE OF THE URINARY BLADDER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Ando, Naokatsu; Taki, Naoya; Kumabe, Ayako; Nishimura, Yoshioki; Kudo, Michiko; Kenzaka, Tsuneaki; Matsumura, Masami] Jichi Med Univ, Shimotsuke, Japan. [Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S415 EP S415 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202290 ER PT J AU Atlas, SJ Jernigan, M Ashbumer, JM Chang, J Borowsky, LH Chang, YC Grant, RW AF Atlas, Steven J. Jernigan, Michael Ashbumer, Jeffrey M. Chang, Jaime Borowsky, Leila H. Chang, Yuchiao Grant, Richard W. TI THE MEDICATION METRONOME: A HEALTH IT SYSTEM TO IMPROVE MEDICATION MANAGEMENT AND LABORAIHRY MONITORING FOR CHRONIC DISEASES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Atlas, Steven J.; Jernigan, Michael; Ashbumer, Jeffrey M.; Chang, Jaime; Borowsky, Leila H.; Chang, Yuchiao] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grant, Richard W.] Kaiser Permanente No Calif, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S230 EP S230 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201175 ER PT J AU Azari, S Hurstak, EE Julian, K Dulay, MH Patel, S AF Azari, Soraya Hurstak, Emily E. Julian, Katherine Dulay, Maya H. Patel, Shalini TI CONTINUITY CLINIC IMMERSION FOR INTERNAL MEDICINE INTERNS: IMPROVING EFFICACY IN AMBULATORY CARE EARLY IN RESIDENCY TRAINING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Azari, Soraya; Hurstak, Emily E.; Julian, Katherine; Dulay, Maya H.; Patel, Shalini] UCSF, San Francisco, CA USA. [Hurstak, Emily E.; Dulay, Maya H.; Patel, Shalini] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S512 EP S512 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203098 ER PT J AU Bachhuber, M Patel, S Kim, C O'Brien, B Shunk, RL AF Bachhuber, Melissa Patel, Shalini Kim, Candace O'Brien, Bridget Shunk, Rebecca L. TI AN INTERPROFESSIONAL CARE TRANSITIONS CURRICULUM FOR AMBULATORY INTERNAL MEDICINE RESIDENTS AND NURSE PRACTITIONER STUDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Bachhuber, Melissa; Patel, Shalini; Kim, Candace; O'Brien, Bridget; Shunk, Rebecca L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Bachhuber, Melissa; Patel, Shalini; O'Brien, Bridget; Shunk, Rebecca L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S507 EP S507 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203086 ER PT J AU Bachhuber, M Broering, J Welles, C Wallhagen, M AF Bachhuber, Melissa Broering, Jeanette Welles, Christine Wallhagen, Margaret TI TRANSFORMING CARE TRANSITIONS: IMPLEMENTING PROJECT RED AT A VETERANS AFFAIRS MEDICAL CENTER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Bachhuber, Melissa; Broering, Jeanette] San Francisco VA Med Ctr, San Francisco, CA USA. [Bachhuber, Melissa; Broering, Jeanette; Wallhagen, Margaret] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Welles, Christine] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S499 EP S499 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203067 ER PT J AU Baggett, TP Chang, YC Porneala, B Gaeta, JM O'Connell, JJ Rigotti, NA AF Baggett, Travis P. Chang, Yuchiao Porneala, Bianca Gaeta, Jessie M. O'Connell, James J. Rigotti, Nancy A. TI ESTIMATING TOBACCO-, ALCOHOL-, AND DRUG-ATTRIBUTABLE DEATHS AND THEIR CONTRIBUTION TO MORTALITY DISPARITIES AMONG HOMELESS ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Baggett, Travis P.; Chang, Yuchiao; Porneala, Bianca; O'Connell, James J.; Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Baggett, Travis P.; Gaeta, Jessie M.; O'Connell, James J.] Boston Hlth Care Homeless Program, Boston, MA USA. [Gaeta, Jessie M.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S87 EP S87 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200211 ER PT J AU Barahimi, M Beste, L AF Barahimi, Mitra Beste, Lauren TI TOO MUCH OF "A" GOOD THING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Barahimi, Mitra; Beste, Lauren] Univ Washington, Seattle, WA 98195 USA. [Beste, Lauren] VA Puget Sound Healthcare Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S457 EP S458 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202411 ER PT J AU Baughman, A Chuang, WR Gace, D Hunt, DP AF Baughman, Amy Chuang, Warren Gace, Denisa Hunt, Daniel P. TI DETERMINING THE ACADEMIC HOSPITALIST SAFE CENSUS: RESULTS FROM A PHYSICIAN SURVEY AND HOSPITALIST SERVICE ANALYSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Baughman, Amy; Chuang, Warren; Gace, Denisa; Hunt, Daniel P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Baughman, Amy] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S66 EP S66 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200163 ER PT J AU Bearnot, BI Magantolo, N Kharsany, AB AF Bearnot, Benjamin I. Magantolo, Nomonde Kharsany, Ayesha B. TI TARGETED IMPROVEMENTS IN HIV COUNSELING AND TESTING SERVICES ON A LARGE UNIVERSITY CAMPUS IN DURBAN, SOUTH AFRICA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Bearnot, Benjamin I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bearnot, Benjamin I.; Magantolo, Nomonde; Kharsany, Ayesha B.] Univ KwaZulu Natal, Durban, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S218 EP S218 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201146 ER PT J AU Bergman, AA Frankel, RM Hamilton, AB Yano, EM AF Bergman, Alicia A. Frankel, Richard M. Hamilton, Alison B. Yano, Elizabeth M. TI WOMEN VETERANS' EXPERIENCES AND PREFERENCES WITH VA PRIMARY CARE: A QUALITATIVE STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Bergman, Alicia A.; Hamilton, Alison B.; Yano, Elizabeth M.] Greater Los Angeles VA Healthcare Syst, North Hills, CA USA. [Frankel, Richard M.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S259 EP S260 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201238 ER PT J AU Bharmal, N Clarke, R Di Capua, P Gupta, I Doyle, B Ali, A Malim, A Mittman, BS AF Bharmal, Nazleen Clarke, Robin Di Capua, Paul Gupta, Indu Doyle, Brian Ali, Aliza Malim, Asad Mittman, Brian S. TI DEVELOPMENT AND APPLICATION OF A CLASSIFICATION SCHEME FOR CARE COORDINATION ACTIVITIES IN AN ACADEMIC PRIMARY CARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Bharmal, Nazleen; Clarke, Robin; Di Capua, Paul; Gupta, Indu; Doyle, Brian] Univ Calif Los Angeles, Los Angeles, CA USA. [Ali, Aliza] Lake Erie Coll Osteopath Med, Bradenton, FL USA. [Malim, Asad] Charles R Drew Univ Med & Sci, Coll Sci & Hlth, Los Angeles, CA 90059 USA. [Mittman, Brian S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mittman, Brian S.] Kaiser Permanente So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S67 EP S67 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200165 ER PT J AU Bharmal, N Mittman, BS Shah, R Sarkisian, C AF Bharmal, Nazleen Mittman, Brian S. Shah, Raina Sarkisian, Catherine TI CULTURAL TAILORING OF STROKE RISK FACTOR REDUCTION AND WALKING PROMOTION COMMUNITY INTERVENTION FOR SOUTH ASIAN OLDER ADULT IMMIGRANTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Bharmal, Nazleen; Sarkisian, Catherine] Univ Calif Los Angeles, Los Angeles, CA USA. [Mittman, Brian S.; Sarkisian, Catherine] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Shah, Raina] Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S60 EP S61 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200148 ER PT J AU Brandenburg, S Brandenburg, C Anderson, M AF Brandenburg, Suzanne Brandenburg, Cynthia Anderson, Mel TI ADAPTING TO A MILLENNIAL LEARNING ENVIRONMENT: AN INTERNAL MEDICINE RESIDENCY CURRICULAR IMPROVEMENT PROJECT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Brandenburg, Suzanne; Anderson, Mel] Univ Colorado, Aurora, CO USA. [Brandenburg, Cynthia] Champlain Coll, Burlington, VT USA. [Anderson, Mel] Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S505 EP S505 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203081 ER PT J AU Burke, R Jones, J Bekelman, D AF Burke, Robert Jones, Jacqueline Bekelman, David TI ROLES DESIRED BY CAREGIVERS OF PATIENTS WITH HEART FAILURE: IMPLICATIONS FOR CLINICIANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Burke, Robert; Bekelman, David] Denver VA Med Ctr, Denver, CO USA. [Burke, Robert; Jones, Jacqueline; Bekelman, David] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S204 EP S205 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201114 ER PT J AU Burke, R Jones, CD Levy, C Ginde, A AF Burke, Robert Jones, Christine D. Levy, Cari Ginde, Add TI RESIDENTIAL CARE FACILITIES' ABILITY TO COMMUNICATE WITH HOSPITALS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Burke, Robert] Denver VA Med Ctr, Denver, CO USA. [Burke, Robert; Jones, Christine D.; Levy, Cari; Ginde, Add] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S201 EP S202 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201106 ER PT J AU Cai, S White, KT Hoffman, B AF Cai, Sophie White, Khendi T. Hoffman, Brian TI AN UNEXPECTED CASE OF ACUTE HEPATITIS C SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Cai, Sophie; Hoffman, Brian] Harvard Univ, Sch Med, Boston, MA USA. [Cai, Sophie; White, Khendi T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hoffman, Brian] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S310 EP S311 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201381 ER PT J AU Carter, JACA Crevensten, G AF Carter, Jocelyn A. Carter A. Crevensten, Gwen TI STAAR: IMPROVING THE RELIABUTTY OF CARE COORDENATION AND REDUCENG HOSPITAL READMISSIONS IN AN ACADEMIC MEDICAL CENTER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Carter, Jocelyn A. Carter A.; Crevensten, Gwen] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S495 EP S496 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203060 ER PT J AU Carter, JACA AF Carter, Jocelyn A. Carter A. TI A CASE OF FEVER AND ABDOMINAL PAIN IN A YOUNGER GENTLEMAN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Carter, Jocelyn A. Carter A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S266 EP S266 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201256 ER PT J AU Cascino, T Mckee, K Kohlwes, J AF Cascino, Thomas Mckee, Kanako Kohlwes, Jeff TI ONE OF THESE THINGS IS NOT LIKE THE OTHER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Cascino, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mckee, Kanako; Kohlwes, Jeff] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S400 EP S401 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202251 ER PT J AU Cordasco, KM Zuchowski, J Hamilton, AB Knapp, H Saavedra, JO Washington, DL AF Cordasco, Kristina M. Zuchowski, Jessica Hamilton, Alison B. Knapp, Herschel Saavedra, Joann O. Washington, Donna L. TI VHA'S COMPREHENSIVE WOMEN'S HEALTH SCAN-ECHO PROGRAM: LESSONS LEARNED SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Cordasco, Kristina M.; Zuchowski, Jessica; Hamilton, Alison B.; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. [Knapp, Herschel; Saavedra, Joann O.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cordasco, Kristina M.; Hamilton, Alison B.; Washington, Donna L.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S542 EP S542 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203171 ER PT J AU Eastman, A Chapman, E Jensen, L Bottoms, HI Thompson, M Vogelman, B Kind, AJ AF Eastman, Alexis Chapman, Elizabeth Jensen, Laury Bottoms, Holly I. Thompson, Mary Vogelman, Bennett Kind, Amy J. TI ASSESSING THE IMPACT OF A RESIDENT COORDINATED TRANSITIONAL CARE ROTATION ON RESIDENT ALTITUDES TOWARDS PATIENT TRANSITIONS AND HEALTH MANAGEMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Eastman, Alexis; Chapman, Elizabeth; Vogelman, Bennett] Univ WI Hosp & Clin, Madison, WI USA. [Chapman, Elizabeth; Thompson, Mary; Vogelman, Bennett; Kind, Amy J.] Univ Wisconsin, Madison, WI USA. [Jensen, Laury; Kind, Amy J.] Madison VA Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Bottoms, Holly I.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S29 EP S29 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200072 ER PT J AU Edwards, ST Prentice, J Simon, SR Pizer, SD AF Edwards, Samuel T. Prentice, Julia Simon, Steven R. Pizer, Steven D. TI HOME-BASED PRIMARY CARE IS ASSOCIATED WITH REDUCED AMBULATORY CARE SENSITIVE HOSPITALIZATIONS IN VETERANS WITH :DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Edwards, Samuel T.; Prentice, Julia; Simon, Steven R.; Pizer, Steven D.] VA Boston Healthcare Syst, Boston, MA USA. [Edwards, Samuel T.] Harvard Univ, Sch Med, Boston, MA USA. [Prentice, Julia] Boston Univ, Boston, MA 02215 USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pizer, Steven D.] Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S109 EP S109 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200260 ER PT J AU Edwards, ST Bitton, A Hong, JS Landon, BE AF Edwards, Samuel T. Bitton, Asaf Hong, Johan S. Landon, Bruce E. TI A NATIONAL SURVEY OF PATIENT CENTERED MEDICAL HOME INITIATIVES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Edwards, Samuel T.] Boston VA Healthcare Syst, Boston, MA USA. [Edwards, Samuel T.; Bitton, Asaf; Hong, Johan S.; Landon, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Bitton, Asaf] Brigham & Womens Hosp, Boston, MA 02115 USA. [Landon, Bruce E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S10 EP S11 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200025 ER PT J AU Englander, H Michaels, L Chan, B Kansagara, D AF Englander, Honora Michaels, LeAnn Chan, Benjamin Kansagara, Devan TI THE CARE TRANSITIONS INNOVATION (C-TRAIN) FOR SOCIOECO-NOMICALLY DISADVANTAGED ADULTS, RESULTS OF A CLUSTERED RANDOMIZED CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Englander, Honora; Kansagara, Devan] Oregon Hlth & Sci Univ, Portand, OR USA. [Michaels, LeAnn; Chan, Benjamin] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kansagara, Devan] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S221 EP S221 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201154 ER PT J AU Flickinger, TE Saha, S Roter, DL Korthuis, PT Sharp, VL Cohn, JA Moore, RD Beach, MC AF Flickinger, Tabor E. Saha, Somnath Roter, Debra L. Korthuis, Philip T. Sharp, Victoria L. Cohn, Jonathan A. Moore, Richard D. Beach, Mary Catherine TI IS HEALTHCARE PROVIDERS' RESPECT FOR PATIENTS ASSOCIATED WITH COMMUNICATION BEHAVIORS IN CLINICAL ENCOUNTERS? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Flickinger, Tabor E.] Univ Virginia, Charlottesville, VA USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Saha, Somnath; Korthuis, Philip T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Roter, Debra L.; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD USA. [Sharp, Victoria L.] St Lukes Roosevelt, New York, NY USA. [Cohn, Jonathan A.] Wayne State Univ, Detroit, MI USA. RI Roter, Debra/N-8830-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S133 EP S133 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200316 ER PT J AU Freund, K Raj, A Terrin, N Kaplan, S Urech, T Pathak, S Carr, P AF Freund, Karen Raj, Anita Terrin, Norma Kaplan, Samantha Urech, Tracy Pathak, Subash Carr, Phyllis TI PROGRESS OR STALEMATE IN ACADEMIC GENDER DISPARITIES? 15 YEAR FOLLOW UP OF THE NATIONAL FACULTY SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Freund, Karen; Terrin, Norma] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Freund, Karen; Terrin, Norma; Urech, Tracy; Pathak, Subash] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Raj, Anita] Univ Calif San Diego, San Diego, CA 92103 USA. [Kaplan, Samantha] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kaplan, Samantha] Boston Med Ctr, Boston, MA USA. [Carr, Phyllis] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S184 EP S185 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201069 ER PT J AU Gopalan, A McDottough, KH Kellom, K Schapira, MM AF Gopalan, Anjali McDottough, Kevin H. Kellom, Katherine Schapira, Marilyn M. TI USING PATIENT FEEDBACK TO EXPLORE AND IMPROVE DIABETES CONTROL COMMUNICATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Gopalan, Anjali; Schapira, Marilyn M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gopalan, Anjali; Kellom, Katherine; Schapira, Marilyn M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [McDottough, Kevin H.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S246 EP S247 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201212 ER PT J AU Gopalan, A Lorincz, I Wirtalla, C Long, JA Marcus, SC AF Gopalan, Anjali Lorincz, Ilona Wirtalla, Christopher Long, Judith A. Marcus, Steven C. TI AWARENESS OF PREDIABETES AND ENGAGEMENT IN DIABETES RISK-REDUCING BEHAVIORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Gopalan, Anjali; Long, Judith A.; Marcus, Steven C.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gopalan, Anjali; Lorincz, Ilona; Wirtalla, Christopher; Long, Judith A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S37 EP S37 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200094 ER PT J AU Grande, D Mitra, N Wan, F Shah, A Asch, DA AF Grande, David Mitra, Nandita Wan, Fei Shah, Anand Asch, David A. TI PATIENT PREFERENCES FOR CONSENT FOR SECONDARY USES OF ELECTRONIC HEALTH INFORMATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Grande, David; Mitra, Nandita; Wan, Fei; Asch, David A.] Univ Penn, Philadelphia, PA 19104 USA. [Shah, Anand] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Shah, Anand] PCCI, Dallas, TX USA. [Asch, David A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S167 EP S167 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201031 ER PT J AU Grant, RW Borowsky, LH Ashburner, JM Jernigan, M Atlas, SJ AF Grant, Richard W. Borowsky, Leila H. Ashburner, Jeffrey M. Jernigan, Michael Atlas, Steven J. TI PRIMARY CARE PROVIDER EXPERIENCE WITH A NEW HEALTH INFORMATION TECHNOLOGY TOOL TO FACILITATE BETWEEN VISIT MEDICATION MANAGEMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Borowsky, Leila H.; Ashburner, Jeffrey M.; Jernigan, Michael; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grant, Richard W.] Kaiser Permanente, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S182 EP S182 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201064 ER PT J AU Greene, M Ritchie, C Martin, J Madamba, JA Mattes, M Miao, YH Deeks, S Valcour, V AF Greene, Meredith Ritchie, Christine Martin, Jeff Madamba, Joy A. Mattes, Monica Miao, Yinghui Deeks, Steven Valcour, Victor TI AGING WITH HIV: SYMPTOM BURDEN AND IMPACT ON QUALITY OF LIFE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Greene, Meredith; Ritchie, Christine; Martin, Jeff; Madamba, Joy A.; Deeks, Steven; Valcour, Victor] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Greene, Meredith; Miao, Yinghui] San Francisco VA Med Ctr, San Francisco, CA USA. [Mattes, Monica] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S18 EP S18 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200046 ER PT J AU Griffith, MF Donaldson, D Young, EA Burke, R AF Griffith, Matthew F. Donaldson, Darcy Young, Eric A. Burke, Robert TI A NOVEL APPROACH TO INTERPROFESSIONAL EDUCATION (IPE) FOR RESTDENTS ON AN INPATIENT MEDICAL SERVICE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Griffith, Matthew F.; Young, Eric A.; Burke, Robert] Univ Colorado, Aurora, CO USA. [Donaldson, Darcy; Young, Eric A.; Burke, Robert] Denver Vet Affairs Hosp, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S502 EP S503 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203075 ER PT J AU Griffiths, C Moote, M Becker, C Wietzke, J Brant, AN Nielsen, D Bernstein, SJ Flanders, SA AF Griffiths, Claire Moote, Marc Becker, Carol Wietzke, Julie Brant, Amy N. Nielsen, Daniel Bernstein, Steven J. Flanders, Scott A. TI HOW WELL DOES MEDICARE'S VTE-1 CORE MEASURE CAPTURE HOSPITAL PERFORMANCE FOR VENOUS THROIVIBOEMBOLISM PROPHYLAXIS? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Griffiths, Claire; Moote, Marc; Becker, Carol; Wietzke, Julie; Brant, Amy N.; Nielsen, Daniel; Bernstein, Steven J.; Flanders, Scott A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Bernstein, Steven J.] US Dept Vet Affairs, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S113 EP S113 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200270 ER PT J AU Hanchate, AD Bradley, SM Kapoor, A McCormick, D Lasser, KE Feng, C Kressin, NR AF Hanchate, Amresh D. Bradley, Steven M. Kapoor, Alok McCormick, Danny Lasser, Karen E. Feng, Chen Kressin, Nancy R. TI MASSACHUSETTS HEALTH CARE REFORM REDUCED RACIAL/ETHNIC DISPARITIES IN ELECTIVE PERCUTANEOUS CORONARY INTERVENTION AND CORONARY ARTERY BYPASS GRAFT SURGERY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hanchate, Amresh D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.; Kapoor, Alok; Lasser, Karen E.; Feng, Chen; Kressin, Nancy R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bradley, Steven M.] VA Eastern Colorado Healthcare Syst, Denver, CO USA. [Bradley, Steven M.] Univ Colorado, Denver, CO 80202 USA. [McCormick, Danny] Cambridge Hlth Alliance, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S146 EP S147 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200342 ER PT J AU Hanson, JT AF Hanson, Joshua T. TI A DEADLY SORE THROAT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hanson, Joshua T.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hanson, Joshua T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S274 EP S275 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201278 ER PT J AU Helfrich, C Simonetti, J Reid, R Joos, S Wakefield, BJ Randall, IA Schectman, G Stark, R Fihn, SD Harvey, HB Nelson, KM AF Helfrich, Christian Simonetti, Joseph Reid, Robert Joos, Sandra Wakefield, Bonnie J. Randall, Ian A. Schectman, Gordon Stark, Richard Fihn, Stephan D. Harvey, Henry B. Nelson, Karin M. TI ELEMENTS OF TEAM-BASED CARE IN A PATIENT-CENTERED MEDICAL HOME ARE ASSOCIATED WITH LOWER BURNOUT AMONG VA PRIMARY CARE EMPLOYEES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Helfrich, Christian; Simonetti, Joseph; Randall, Ian A.; Fihn, Stephan D.; Harvey, Henry B.; Nelson, Karin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. [Joos, Sandra] Dept Vet Affairs, Portland, OR USA. [Wakefield, Bonnie J.] Dept Vet Affairs, Iowa City, IA USA. [Schectman, Gordon; Stark, Richard] Vet Hlth Adm, Washington, DC USA. [Reid, Robert] Grp Hlth, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S84 EP S85 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200204 ER PT J AU Hostetler, RL Markowitz, JS AF Hostetler, Rebecca L. Markowitz, Jeremy S. TI A TIGHT SQUEEZE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hostetler, Rebecca L.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Markowitz, Jeremy S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S289 EP S289 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201317 ER PT J AU Hsu, A Nakagawa, S Walter, L Van den Eeden, SK Brown, JS Thom, D Lee, S Huang, AJ AF Hsu, Amy Nakagawa, Sanae Walter, Louise Van den Eeden, Stephen K. Brown, Jeanette S. Thom, David Lee, Sei Huang, Alison J. TI LOOKING BEYOND THE PROSTATE: DETERMINANTS AND IMPACT OF NOCTURIA IN MIDDLE-AGED AND OLDER WOMEN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hsu, Amy; Walter, Louise; Lee, Sei] San Francisco VA Med Ctr, San Francisco, CA USA. [Nakagawa, Sanae; Brown, Jeanette S.; Thom, David; Huang, Alison J.] Univ Calif San Francisco, San, CA USA. [Van den Eeden, Stephen K.] Kaiser Permanente Div Res, San, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S141 EP S141 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200333 ER PT J AU Hwang, AS Liu, SW Yelibi, C Ashbumer, JM He, W Auerbach, B Atlas, SJ Hong, CS AF Hwang, Andrew S. Liu, Shan W. Yelibi, Carine Ashbumer, Jeffrey M. He, Wei Auerbach, Brandon Atlas, Steven J. Hong, Clemens S. TI CHARACTERISTICS OF PERSISTENT EMERGENCY DEPARTMENT HIGH UTILIZERS IN A LARGE PRIMARY CARE PRACTICE-BASED RESEARCH NETWORK SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hwang, Andrew S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Liu, Shan W.; Yelibi, Carine; Ashbumer, Jeffrey M.; He, Wei; Auerbach, Brandon; Atlas, Steven J.; Hong, Clemens S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S47 EP S47 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200116 ER PT J AU Hwang, AS Atlas, SJ Cronin, PR Ashburner, JM Shah, SJ He, W Hong, CS AF Hwang, Andrew S. Atlas, Steven J. Cronin, Patrick R. Ashburner, Jeffrey M. Shah, Sachin J. He, Wei Hong, Clemens S. TI ASSOCIATION BETWEEN OUTPATIENT "NO-SHOWS" AND SUBSEQUENT ACUTE CARE UTILIZATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hwang, Andrew S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Atlas, Steven J.; Cronin, Patrick R.; Ashburner, Jeffrey M.; Shah, Sachin J.; He, Wei; Hong, Clemens S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S31 EP S32 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200079 ER PT J AU Hwang, AS Atlas, SJ Cronin, PR Ashburner, JM Shah, SJ He, W Hong, CS AF Hwang, Andrew S. Atlas, Steven J. Cronin, Patrick R. Ashburner, Jeffrey M. Shah, Sachin J. He, Wei Hong, Clemens S. TI ASSOCIATION BETWEEN OUTPATIENT' "NO-SHOWS" AND SUBSEQUENT CLINICAL OUTCOMES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hwang, Andrew S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Atlas, Steven J.; Cronin, Patrick R.; Ashburner, Jeffrey M.; Shah, Sachin J.; He, Wei; Hong, Clemens S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S32 EP S32 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200080 ER PT J AU Jeffries, EC Ward, CE Cohen, MJ AF Jeffries, Emma C. Ward, Charlotte E. Cohen, Marya J. TI EMPATHY, CAREER INTERESTS, AND FACTORS INFLUENCING CAREER CHOICE AMONG MEDICAL STUDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Jeffries, Emma C.; Ward, Charlotte E.; Cohen, Marya J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S85 EP S85 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200205 ER PT J AU Johnson, K Simon, N Wicks, M Schaad, D Barr, KP O'Connor, K AF Johnson, Kay Simon, Nancy Wicks, Mark Schaad, Doug Barr, Karen P. O'Connor, Kim TI SLEEP HABITS, QUALITY OF LIFE AND SATISFACTION WITH ACADEMIC SUCCESS IN SECOND YEAR MEDICAL STUDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Johnson, Kay; Simon, Nancy; Wicks, Mark; Schaad, Doug; Barr, Karen P.; O'Connor, Kim] Univ Washington, Sch Med, Seattle, WA USA. [Johnson, Kay] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S209 EP S209 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201125 ER PT J AU Kangovi, S Kellom, K Sha, C Johnson, S Chanton, C Carter, T Long, JA Grande, D AF Kangovi, Shreya Kellom, Katherine Sha, Christopher Johnson, Sarah Chanton, Casey Carter, Tamala Long, Judith A. Grande, David TI PATIENT AND PROVIDER PERCEPTIONS OF THE PATIENT CENTERED MEDICAL HOME: AGREEMENT AND TENSIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Kangovi, Shreya; Carter, Tamala; Long, Judith A.; Grande, David] Univ Penn, Perelman Sch Med, Phialdelphia, PA USA. [Kangovi, Shreya; Chanton, Casey] Univ Penn Hlth Syst, Philadelphia, PA USA. [Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kellom, Katherine; Carter, Tamala; Grande, David] Univ Penn, Philadelphia, PA 19104 USA. [Sha, Christopher] Univ San Francisco, San Francisco, CA 94117 USA. [Johnson, Sarah] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S165 EP S165 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201027 ER PT J AU Kansagara, D McCiain, M Englander, H Peters, D Morris, CD AF Kansagara, Devan McCiain, Molly Englander, Honora Peters, Dawn Morris, Cynthia D. TI PATIENT ACTIVATION MEASURE AND CARE TRANSITIONS AMONG SOCIOECONOMICALLY VULNERABLE ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Kansagara, Devan; McCiain, Molly; Englander, Honora; Peters, Dawn; Morris, Cynthia D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kansagara, Devan] Portland VA Med Ctr, Portland, OR USA. [McCiain, Molly] Univ New Mexico, Albuqurque, NM USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S165 EP S165 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201026 ER PT J AU Karwowski, E Miller, AR Sarfaty, S AF Karwowski, Elizabeth Miller, Alexa R. Sarfaty, Suzanne TI VISUAL THINKING STRATEGIES: AN ARTS-BASED INTERVENTION TO TEACH TEAMWORK TO SENIOR MEDICAL STUDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Karwowski, Elizabeth; Sarfaty, Suzanne] Boston Univ, Med Ctr, Boston, MA USA. [Karwowski, Elizabeth] Boston VA Healthcare Syst, Boston, MA USA. [Miller, Alexa R.] Brandeis Univ, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S543 EP S543 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203173 ER PT J AU Karwowski, E Sandman, E Liebschutz, JM Fraser, B Orlander, JD AF Karwowski, Elizabeth Sandman, Elizabeth Liebschutz, Jane M. Fraser, Bruce Orlander, Jay D. TI FACULTY PERCEPTIONS OF COMPETENCY-BASED EVALUATION OF MEDICAL STUDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Karwowski, Elizabeth; Liebschutz, Jane M.; Orlander, Jay D.] Boston Univ, Med Ctr, Boston, MA USA. [Karwowski, Elizabeth; Sandman, Elizabeth; Orlander, Jay D.] Boston VA Healthcare Syst, Boston, MA USA. [Fraser, Bruce] Boston Univ, Sch Educ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S97 EP S97 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200230 ER PT J AU Kertesz, S Holmes, S White, B Pollio, DE Austin, EL Schumacher, JE Lukas, CV AF Kertesz, Stefan Holmes, Sally White, Bert Pollio, David E. Austin, Erika L. Schumacher, Joseph E. Lukas, Carol VanDeusen TI MAKING HOUSING FIRST HAPPEN: ORGANIZATIONAL ACTIONS THAT AFFECT SUCCESS AMONG VA MEDICAL CENTERS IN ENDING HOMELESSNESS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Kertesz, Stefan; Austin, Erika L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kertesz, Stefan; Pollio, David E.; Austin, Erika L.; Schumacher, Joseph E.] Univ Alabama Birmingham, Birmingham, AL USA. [Holmes, Sally; White, Bert; Lukas, Carol VanDeusen] Boston VA Med Ctr, Boston, MA USA. [Holmes, Sally; Lukas, Carol VanDeusen] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S143 EP S143 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200337 ER PT J AU Kiefer, MM Silverman, JB Nelson, KM AF Kiefer, Meghan M. Silverman, Julie B. Nelson, Karin M. TI RACIAL AND ETHNIC DIFFERENCES IN SCREENING FOR DIABETES MELLITUS: NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2005-2012 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Kiefer, Meghan M.; Silverman, Julie B.; Nelson, Karin M.] Univ Washington, Sch Med, Seattle, WA USA. [Kiefer, Meghan M.; Silverman, Julie B.; Nelson, Karin M.] VA Puget Sound Healthcare Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S190 EP S190 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201082 ER PT J AU Klein, JW Evans, GA Golob, A Rhoads, C AF Klein, Jared W. Evans, Ginger A. Golob, Anna Rhoads, Caroline TI ACCELERATING AMBULATORY APLOMB: A NOVEL IMMERSION BLOCK CURRICULUM FOR INTRODUCING INTERNAL MEDICINE HIS TO CONTINUITY CLINIC SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Klein, Jared W.; Evans, Ginger A.; Golob, Anna; Rhoads, Caroline] Univ Washington, Seattle, WA 98195 USA. [Klein, Jared W.; Rhoads, Caroline] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Evans, Ginger A.; Golob, Anna] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S505 EP S505 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203080 ER PT J AU Kullgren, JT Dicks, TN Fu, XY Tzanis, GL Tobi, M Marcus, SC AF Kullgren, Jeffrey T. Dicks, Tanisha N. Fu, Xiaoying Tzanis, George L. Tobi, Martin Marcus, Steven C. TI FINANCIAL INCENTIVES FOR COMPLETION OF FECAL OCCULT BLOOD TESTS AMONG VETERANS: A 2-STAGE PRAGMATIC CLUSTER RANDOMIZED, CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Kullgren, Jeffrey T.] Ann Arbor VA Healthcare Syst, Ann Arbor, MI USA. [Kullgren, Jeffrey T.] Univ Michigan, Ann Arbor, MI 48109 USA. [Dicks, Tanisha N.; Fu, Xiaoying; Tzanis, George L.; Tobi, Martin; Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Tzanis, George L.; Tobi, Martin; Marcus, Steven C.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S98 EP S98 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200234 ER PT J AU Lasser, KE Chu, C McCormick, D Hanchate, AD Kressin, NR AF Lasser, Karen E. Chu, Chieh McCormick, Danny Hanchate, Amresh D. Kressin, Nancy R. TI MASSACHUSETTS HEALTH REFORM WAS ASSOCIATED WITH MOVEMENT OF INPATIENT CARE FROM SAFETY-NET TO NON-SAFETY-NET HOSPITALS AMONG FREQUENTLY HOSPITALIZED PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Hanchate, Amresh D.; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Lasser, Karen E.; Chu, Chieh; Hanchate, Amresh D.; Kressin, Nancy R.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [McCormick, Danny] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. [Lasser, Karen E.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S147 EP S147 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200343 ER PT J AU Lee, JJ Sgro, G AF Lee, Jane J. Sgro, Gaetan TI THE UNUSUAL SUSPECT: PARANEOPLASTIC MONONEURITIS MULTIPLEX SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Lee, Jane J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sgro, Gaetan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S451 EP S451 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202393 ER PT J AU Levander, XA Takahashi, TA Ma, M AF Levander, Ximena A. Takahashi, Traci A. Ma, Maxwell TI REVERSIBLE MYELONEUROPATHY IN A YOUNG WOMAN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Levander, Ximena A.; Takahashi, Traci A.; Ma, Maxwell] Univ Washington, Seattle, WA 98195 USA. [Takahashi, Traci A.] VA Puget Sound Healthcare Syst, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S426 EP S427 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202324 ER PT J AU Levitt, DS Meo, N Chen, CP Murphy, CM Vanderwarker, C Wipf, JE Kaminetzky, CP AF Levitt, David S. Meo, Nicholas Chen, Christopher P. Murphy, Christopher M. Vanderwarker, Christopher Wipf, Joyce E. Kaminetzky, Catherine P. TI QUALITY INITIATIVE TO INCREASE PROVIDER USE OF URINE DRUG TESTING FOR CHRONIC PAIN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Levitt, David S.; Meo, Nicholas; Chen, Christopher P.; Murphy, Christopher M.; Vanderwarker, Christopher; Wipf, Joyce E.; Kaminetzky, Catherine P.] Univ Washington, Seattle, WA 98195 USA. [Levitt, David S.; Meo, Nicholas; Chen, Christopher P.; Murphy, Christopher M.; Vanderwarker, Christopher; Wipf, Joyce E.; Kaminetzky, Catherine P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S493 EP S493 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203055 ER PT J AU Linder, JA Haas, J Rigotti, NA Park, ER Kontos, E Gonzalez, I Klinger, E Marinacci, L Brawarsky, P St Hubert, S AF Linder, Jeffrey A. Haas, Jennifer Rigotti, Nancy A. Park, Elyse R. Kontos, Emily Gonzalez, Irina Klinger, Elissa Marinacci, Lucas Brawarsky, Phyllis St Hubert, Stella TI PROACTIVE OUTREACH OF TOBACCO CESSATION TREATMENT TO DISADVANTAGED SMOKERS AFTER A PRIMARY CARE VISIT: A RANDOMIZED CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Linder, Jeffrey A.; Haas, Jennifer; Gonzalez, Irina; Klinger, Elissa; Marinacci, Lucas; Brawarsky, Phyllis; St Hubert, Stella] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rigotti, Nancy A.; Park, Elyse R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Linder, Jeffrey A.; Haas, Jennifer; Rigotti, Nancy A.; Park, Elyse R.] Harvard Univ, Sch Med, Boston, MA USA. [Kontos, Emily] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kontos, Emily] Lung Canc Dispar Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S184 EP S184 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201067 ER PT J AU Linsky, A Simon, SR Bokhour, BC AF Linsky, Amy Simon, Steven R. Bokhour, Barbara C. TI PATIENT PERCEPTIONS OF INTENTIONAL MEDICATION DISCONTINUATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Linsky, Amy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bokhour, Barbara C.] ENRM Vet Affairs Med Ctr, Bedford, MA USA. [Bokhour, Barbara C.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S166 EP S167 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201030 ER PT J AU Mafi, JN Edwards, ST Pederson, N Davis, RB McCarthy, EP Landon, BE AF Mafi, John N. Edwards, Samuel T. Pederson, Nigel Davis, Roger B. McCarthy, Ellen P. Landon, Bruce E. TI WORSENING TRENDS IN THE AMBULATORY MANAGEMENT OF HEADACHE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Mafi, John N.; Davis, Roger B.; McCarthy, Ellen P.; Landon, Bruce E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Edwards, Samuel T.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Pederson, Nigel] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pederson, Nigel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCarthy, Ellen P.; Landon, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S260 EP S261 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201240 ER PT J AU Maniam, N Slight, SR Seger, DL Amato, M McEvoy, D Nanji, KC Cho, I Dkyes, PC Bates, DW AF Maniam, Nivethietha Slight, Sarah R. Seger, Diane L. Amato, Mary McEvoy, Dustin Nanji, Karen C. Cho, Insook Dkyes, Patricia C. Bates, David W. TI AN EVALUATION OF COMPUTERIZED MEDICATION ALERT OVERRIDE BEHAVIOR IN AMBULATORY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Maniam, Nivethietha; Slight, Sarah R.; Seger, Diane L.; Amato, Mary; McEvoy, Dustin; Cho, Insook; Bates, David W.] Partners HealthCare, Cambridge, MA USA. [Dkyes, Patricia C.; Bates, David W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Slight, Sarah R.] Univ Durham, Sch Med, Stockton On Tees, England. [Nanji, Karen C.; Dkyes, Patricia C.] Harvard Univ, Sch Med, Boston, MA USA. [Nanji, Karen C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cho, Insook] Inha Univ, Inchon, South Korea. [Amato, Mary] Massachusetts Coll Pharm & Allied Hlth Sci, Boston, MA USA. [Amato, Mary] Hlth Sci Univ, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S20 EP S20 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200051 ER PT J AU Mayer, VL Hillier, A Bachhuber, MA Long, JA AF Mayer, Victoria L. Hillier, Amy Bachhuber, Marcus A. Long, Judith A. TI THE RELATIONSHIP BETWEEN NEIGHBORHOOD FOOD ACCESS AND FOOD INSECURITY IN AN URBAN ENVIRONMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Mayer, Victoria L.; Bachhuber, Marcus A.; Long, Judith A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hillier, Amy] Univ Penn, Sch Design, Philadelphia, PA 19104 USA. [Bachhuber, Marcus A.; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S232 EP S232 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201179 ER PT J AU Mayer, VL McDonough, KH Seligman, HK Long, JA AF Mayer, Victoria L. McDonough, Kevin H. Seligman, Hilary K. Long, Judith A. TI FOOD INSECURITY, COPING STRATEGIES, AND GLYCEMIC CONTROL IN LOW-INCOME PATIENTS WITH DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Mayer, Victoria L.; McDonough, Kevin H.; Long, Judith A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Seligman, Hilary K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S101 EP S102 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200241 ER PT J AU McCullough, SA Ufere, N Yeh, A Modi, B Olson, K AF McCullough, Stephen A. Ufere, Nneka Yeh, Albert Modi, Badri Olson, Kristin TI ANCA-ASSOCIATED VASCULITIS PRESENTING AS INTERSTITIAL LUNG DISEASE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [McCullough, Stephen A.; Ufere, Nneka; Yeh, Albert; Modi, Badri; Olson, Kristin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S316 EP S316 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202008 ER PT J AU McCullough, SA Baggett, M Chiappa, V Bazari, H Currier, PF AF McCullough, Stephen A. Baggett, Meridale Chiappa, Victor Bazari, Hasan Currier, Paul F. TI THE EFFECTIVENESS OF A CASE-BASED CURRICUI.A1M ON INTERNAL MEDICINE RESIDENTS' PERCEPTIONS REGARDING APOLOGY FOR MEDICAL ERRORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [McCullough, Stephen A.; Baggett, Meridale; Chiappa, Victor; Bazari, Hasan; Currier, Paul F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S222 EP S222 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201158 ER PT J AU Meo, N Wong, E Bryson, CL Sun, HL Curtis, I Gupta, I Batten, A Fihn, SD Nelson, KM AF Meo, Nicholas Wong, Edwin Bryson, Christopher L. Sun, Haili Curtis, Idamay Gupta, Indra Batten, Adam Fihn, Stephan D. Nelson, Karin M. TI ORGANIZATIONAL FACTORS ASSOCIATED WITH MEDICATION ADHERENCE AFTER PATIENT CENTERED MEDICAL HOME TRANSFORMATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Meo, Nicholas; Bryson, Christopher L.; Fihn, Stephan D.; Nelson, Karin M.] Univ Washington, Seattle, WA 98195 USA. [Wong, Edwin; Bryson, Christopher L.; Sun, Haili; Curtis, Idamay; Gupta, Indra; Batten, Adam; Nelson, Karin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S160 EP S161 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201016 ER PT J AU Merritt, FW Prochazka, AV Aagaard, EM Stickrath, C AF Merritt, Frank W. Prochazka, Allan V. Aagaard, Eva M. Stickrath, Chad TI MEDICINE ATTENDING ROUNDS: FREQUENCY OF OBSERVED TEACHING BEHAVIORS AND LEARNERS' PERCEPTIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Merritt, Frank W.; Prochazka, Allan V.; Aagaard, Eva M.; Stickrath, Chad] Univ Colorado, Sch Med, Denver, CO USA. [Prochazka, Allan V.; Stickrath, Chad] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S149 EP S150 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200349 ER PT J AU Moin, T Steers, N Ettner, S Duru, OK Turk, N Chan, C Luchs, RH Kirvan, A Ho, S Mangione, C AF Moin, Tannaz Steers, Neil Ettner, Susan Duru, O. Kenrik Turk, Norman Chan, Charles Luchs, Robert H. Kirvan, Anya Ho, Sam Mangione, Carol TI THE IMPACT OF A DIABETES-SPECIFIC HEALTH PLAN ON ED AND INPATIENT HOSPITAL USE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Moin, Tannaz] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Moin, Tannaz] HSR&D Ctr Healthcare Innovat, Los Angeles, CA USA. [Moin, Tannaz; Steers, Neil; Ettner, Susan; Duru, O. Kenrik; Turk, Norman; Mangione, Carol] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Chan, Charles; Luchs, Robert H.; Kirvan, Anya; Ho, Sam] UnitedHlth Grp, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S226 EP S227 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201166 ER PT J AU Moin, T Makki, F Weinreb, JE Steinle, N Billington, CJ Havens, K Yancy, W Maciejewski, ML Damschroder, L Richardson, CR AF Moin, Tannaz Makki, Fatima Weinreb, Jane E. Steinle, Nanette Billington, Charles J. Havens, Kathryn Yancy, William Maciejewski, Mathew L. Damschroder, Laura Richardson, Caroline R. TI THE BURDEN OF PRE-DIABETES AMONG OBESE VETERANS: UNDER-STANDLNG THE PREVALENCE OF DISEASE AND MERITS OF ROUTINE SCREENING PROGRAMS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Moin, Tannaz] VA Greater Los Angeles HSR&D Ctr Healthcare Innov, Los Angeles, CA USA. [Moin, Tannaz; Weinreb, Jane E.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Makki, Fatima; Damschroder, Laura] Ann Arbor VA Ctr Clin Management Res, Ann Arbor, MI USA. [Steinle, Nanette] VA Baltimore Healthcare Syst, Baltimore, MD USA. [Steinle, Nanette] Univ Maryland, Baltimore, MD 21201 USA. [Billington, Charles J.] Minneapolis VA Healthcare Syst, Minneapolis, MN USA. [Billington, Charles J.] Univ Minnesota, Milwaukee, MN USA. [Havens, Kathryn] Zablocki VA, Milwaukee, WI USA. [Yancy, William; Maciejewski, Mathew L.] Duke Univ Med Ctr, Durham, NC USA. [Yancy, William; Maciejewski, Mathew L.] Durham VA, Durham, NC USA. [Richardson, Caroline R.] VA Diabet QUERI, Ann Arbor, MI USA. [Richardson, Caroline R.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S220 EP S221 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201153 ER PT J AU Moin, T Li, JN Duru, OK Ettner, S Turk, N Luchs, RH Keckhafer, AM Kirvan, A Mangione, C AF Moin, Tannaz Li, Jinnan Duru, O. Kenrik Ettner, Susan Turk, Norman Luchs, Robert H. Keckhafer, Abigail M. Kirvan, Anya Mangione, Carol TI DIABETES PREVENTION: ARE WE TRANSLATING EVIDENCE INTO PRACTICE? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Moin, Tannaz] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Moin, Tannaz] HSR&D Ctr Healthcare Innovat, Los Angeles, CA USA. [Moin, Tannaz; Li, Jinnan; Duru, O. Kenrik; Ettner, Susan; Turk, Norman; Mangione, Carol] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Luchs, Robert H.; Keckhafer, Abigail M.; Kirvan, Anya] UnitedHlth Grp, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S70 EP S70 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200173 ER PT J AU Morland, TB Synnestvedt, M Honeywell, S Yang, FF Armstrong, K Guerra, CE AF Morland, Thomas B. Synnestvedt, Marie Honeywell, Steven Yang, Feifei Armstrong, Katrina Guerra, Carmen E. TI EFFECT OF FINANCIAL INCENTIVE FOR COLORECTAL CANCER SCREENING ADHERENCE ON APPROPRIATENESS OF COLONOSCOPY ORDERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Morland, Thomas B.] Geisinger Med Ctr, Danville, PA 17822 USA. [Synnestvedt, Marie; Honeywell, Steven; Yang, Feifei; Guerra, Carmen E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S79 EP S79 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200193 ER PT J AU Mortensen, E Halm, E Fine, MJ Johnson, C Anuzeto, A AF Mortensen, Eric Halm, Ethan Fine, Michael J. Johnson, Christopher Anuzeto, Antonio TI AZITHROMYCLIN IS ASSOCIATED WITH INCREASED CARDIAC EVENTS BUT LOWER MORTALITY FOR OLDER PATIENTS HOSPITALIZED WITH PNEUMONIA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Mortensen, Eric; Johnson, Christopher] VANTHCS, Dallas, TX USA. [Mortensen, Eric; Halm, Ethan; Johnson, Christopher] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Fine, Michael J.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Anuzeto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S37 EP S38 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200095 ER PT J AU Musgrove, J Kraemer, R Morris, JL Estrada, C AF Musgrove, John Kraemer, Ryan Morris, Jason L. Estrada, Carlos TI UTILIZING ITERATIVE CASE PRESENTATION TO DEMONSTRATE CONCEPTS OE CLINICAL REASONING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Musgrove, John; Kraemer, Ryan; Morris, Jason L.; Estrada, Carlos] Univ Alabama Birmingham, Birmingham, AL USA. [Kraemer, Ryan; Morris, Jason L.; Estrada, Carlos] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S247 EP S248 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201214 ER PT J AU Musgrove, J Morris, JL Kraemer, R Estrada, C AF Musgrove, John Morris, Jason L. Kraemer, Ryan Estrada, Carlos TI PRIORITIZING CONCEPTS OF CLINICAL REASONING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Musgrove, John; Morris, Jason L.; Kraemer, Ryan; Estrada, Carlos] Univ Alabama Birmingham, Birmingham, AL USA. [Morris, Jason L.; Kraemer, Ryan; Estrada, Carlos] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S183 EP S184 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201066 ER PT J AU Nambudiri, N Nambudiri, VE Tsao, S AF Nambudiri, Navya Nambudiri, Vinod E. Tsao, Sandy TI A RASH ON THE PALMS AND SOLES-AND EVERYWHERE IN BETWEEN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Nambudiri, Vinod E.] Brigham & Women, Brookline, MA USA. [Nambudiri, Vinod E.; Tsao, Sandy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nambudiri, Navya] Cochin Med Coll, Cochin, Kerala, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S285 EP S285 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201308 ER PT J AU Nasir, S Bates, JT AF Nasir, Saifullah Bates, Jeffrey T. TI THYROTOXIC HYPOKALEMIC PERIODIC PARALYSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Nasir, Saifullah; Bates, Jeffrey T.] Baylor Coll Med, Houston, TX 77030 USA. [Nasir, Saifullah; Bates, Jeffrey T.] Houston VAMC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S454 EP S454 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202402 ER PT J AU Nautiyal, K Bates, JI AF Nautiyal, Kirtan Bates, Jeffrey I. TI A SWING AND A MISS: HEPARIN INDUCED THROMBOCYTOPENIA (HIT) WITH AN INITIALLY NEGATIVE ANTIBODY SCREEN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Nautiyal, Kirtan; Bates, Jeffrey I.] Baylor Coll Med, Houston, TX 77030 USA. [Nautiyal, Kirtan; Bates, Jeffrey I.] Michael E DeBakey Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S287 EP S288 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201314 ER PT J AU Nelson, KM Helfrich, C Sun, HL Hebert, P Liu, CF Dolan, ED Taylor, L Wong, E Maynard, C Hernandez, S Sanders, WJ Curtis, I Randall, IA Schectman, G Stark, R Fihn, SD AF Nelson, Karin M. Helfrich, Christian Sun, Haili Hebert, Paul Liu, Chuan-Fen Dolan, Emily D. Taylor, Leslie Wong, Edwin Maynard, Charles Hernandez, Susan Sanders, William J. Curtis, Idamay Randall, Ian A. Schectman, Gordon Stark, Richard Fihn, Stephan D. TI IMPLEMENTATION OF THE PATIENT CENTERED MEDICAL HOME (PCMH) IN THE VETERANS HEALTH ADMINISTRATION (VHA); ASSOCIATIONS WITH CLINICAL OUTCOMES, PATIENT SATISFACTION, PROVIDER BURNOUT AND UTILIZATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Nelson, Karin M.; Helfrich, Christian; Sun, Haili; Hebert, Paul; Liu, Chuan-Fen; Dolan, Emily D.; Taylor, Leslie; Wong, Edwin; Maynard, Charles; Hernandez, Susan; Sanders, William J.; Curtis, Idamay; Randall, Ian A.; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. [Schectman, Gordon; Stark, Richard] Vet Hlth Adm, Washington, DC USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S123 EP S123 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200291 ER PT J AU Nieva, HR Doctor, JN Friedberg, MW Birks, C Kleyner, Y Fiskio, J Volk, LA Linder, JA AF Nieva, Harry Reyes Doctor, Jason N. Friedberg, Mark W. Birks, Caroline Kleyner, Yelena Fiskio, Julie Volk, Lynn A. Linder, Jeffrey A. TI COMPARING CLINICIANS PERCEPTION OF THEIR OWN AND THEIR PEERS' ANTIBIOTIC PRESCRIBING TO ACTUAL ANTIBIOTIC PRESCRIBING FOR ACUTE RESPIRATORY INFECTIONS IN PRIMARY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Nieva, Harry Reyes; Friedberg, Mark W.; Fiskio, Julie; Linder, Jeffrey A.] Brigham & Women, Boston, MA USA. [Nieva, Harry Reyes; Birks, Caroline; Linder, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Doctor, Jason N.] Univ So Calif, Los Angeles, CA USA. [Friedberg, Mark W.] RAND Corp, Boston, MA USA. [Birks, Caroline] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kleyner, Yelena; Volk, Lynn A.] Partners Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S55 EP S55 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200134 ER PT J AU Norcott, A Anderson, E Dann, S Hyson, A Luco, C Meyer, EM Zapatka, SA Brienza, R AF Norcott, Alexandra Anderson, Eskrina Dann, Sarah Hyson, Anne Luco, Cali Meyer, Emily M. Zapatka, Susan A. Brienza, Rebecca TI REDUCING NON-URGENT EMERGENCY ROOM VISITS DURING PRIMARY CARE BUSINESS HOURS: A COLLABORATIVE APPROACH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Norcott, Alexandra; Anderson, Eskrina; Dann, Sarah; Hyson, Anne; Luco, Cali; Meyer, Emily M.; Zapatka, Susan A.; Brienza, Rebecca] US Dept Vet Affairs, West Haven, CT USA. [Norcott, Alexandra; Anderson, Eskrina; Dann, Sarah; Hyson, Anne; Luco, Cali; Meyer, Emily M.; Zapatka, Susan A.; Brienza, Rebecca] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S494 EP S495 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203058 ER PT J AU OBrien, B Keene, T Shunk, RL AF OBrien, Bridget Keene, Terry Shunk, Rebecca L. TI TEAM HUDDLES AS WORKPLACE LEARNING OPPORTUNITIES: AN OBSERVATIONAL STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [OBrien, Bridget; Shunk, Rebecca L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Keene, Terry; Shunk, Rebecca L.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S218 EP S219 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201148 ER PT J AU Overland, MK Pyke, L Poppe, AP Wipf, JE AF Overland, Maryann K. Pyke, Linda Poppe, Anne P. Wipf, Joyce E. TI TEACHING SHARED DECISION MAKING: IMPROVING RESIDENT COMMUNICATION THROUGH CURRICULAR INNOVATION AND OBSERVED VISITS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Overland, Maryann K.; Pyke, Linda; Poppe, Anne P.; Wipf, Joyce E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Overland, Maryann K.; Wipf, Joyce E.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S537 EP S537 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203159 ER PT J AU Pasha, A Kansagara, D Papak, J O'Neil, M Freeman, M Relevo, R Quinones, A Motu'apuaka, M Jou, JH AF Pasha, Amirala Kansagara, Devan Papak, Joel O'Neil, Maya Freeman, Michele Relevo, Rose Quinones, Ana Motu'apuaka, Makalapua Jou, Janice H. TI SCREENING FOR HEPATOCELLULAR CARCINOMA IN CHRONIC LIVER DISEASE: A SYSTEMATIC REVIEW SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Kansagara, Devan; Papak, Joel; O'Neil, Maya; Freeman, Michele; Relevo, Rose; Motu'apuaka, Makalapua; Jou, Janice H.] Portland VA Med Ctr, Portland, OR USA. [Pasha, Amirala; Kansagara, Devan; Papak, Joel; Quinones, Ana; Jou, Janice H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S206 EP S207 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201119 ER PT J AU Percac-Lima, S Cronin, PR Thakkar, A Zai, A AF Percac-Lima, Sanja Cronin, Patrick R. Thakkar, Anjali Zai, Adrian TI IMPROVING ATTENDANCE TO PRIMARY CARE APPOINTMENTS: RANDOMIZED CONTROL TRIAL OF TEXT MESSAGING TO PATIENTS AT A COMMUNITY HEALTH CENTER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Percac-Lima, Sanja] Massachusetts Gen Hosp, Chelsea, MA USA. [Percac-Lima, Sanja; Cronin, Patrick R.; Zai, Adrian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thakkar, Anjali] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S486 EP S486 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203040 ER PT J AU Percac-Lima, S Ashburner, JM Piawah, S McCarthy, AM Atlas, SJ AF Percac-Lima, Sanja Ashburner, Jeffrey M. Piawah, Sorbarikor McCarthy, Anne Marie Atlas, Steven J. TI THE IMPACT OF A COMMUNITY HEALTH CENTER PATIENT :NAVIGATION PROGRAM ON ABNORMAL MAMMOGRAPHY FOLLOW-UP SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Percac-Lima, Sanja; Ashburner, Jeffrey M.; McCarthy, Anne Marie; Atlas, Steven J.] Massachusetts Gen Hosp, Chelsea, MA USA. [Piawah, Sorbarikor] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S226 EP S226 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201165 ER PT J AU Pham, C Kratz, JR McCormick, D AF Pham, Christina Kratz, Johannes R. McCormick, Danny TI CHILDREN: A BARRIER TO MATERNAL HEALTH CARE UTILIZATION? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Kratz, Johannes R.] Massachusetts Gen Hosp, Cambridge, MA USA. [Pham, Christina; McCormick, Danny] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S48 EP S48 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200118 ER PT J AU Raghavan, S Porneala, B Dupuis, J Meigs, JB AF Raghavan, Sridharan Porneala, Bianca Dupuis, Josee Meigs, James B. TI METABOLIC RISK FACTORS AND GENETIC RISK PARTIALLY MEDIATE THE RISK OF TYPE 2 DIABETES CONFERRED BY PARENTAL DIABETES HISTORY IN THE FRAMINGHAM HEART STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Raghavan, Sridharan; Porneala, Bianca; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raghavan, Sridharan; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S150 EP S150 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200350 ER PT J AU Randall, IA Harvey, HB Mohr, D Dolan, ED Nelson, KM Hebert, P Fihn, SD Helfrich, C AF Randall, Ian A. Harvey, Henry B. Mohr, David Dolan, Emily D. Nelson, Karin M. Hebert, Paul Fihn, Stephan D. Helfrich, Christian TI EXPLORING THE ASSOCIATION BETWEEN PATIENT-CENTERED MEDICAL HOME TEAM-BASED CARE ELEMENTS AND EMPLOYEE JOB SATISFACTION AT THE VHA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Randall, Ian A.; Dolan, Emily D.; Nelson, Karin M.; Hebert, Paul; Helfrich, Christian] Univ Washington, Seattle, WA 98195 USA. [Randall, Ian A.; Harvey, Henry B.; Dolan, Emily D.; Nelson, Karin M.; Hebert, Paul; Fihn, Stephan D.; Helfrich, Christian] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Mohr, David] VA Boston Healthcare Syst, Boston, MA USA. [Mohr, David] Boston Univ, Boston, MA 02215 USA. [Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S92 EP S93 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200222 ER PT J AU Rao, SK Thompson, R Milford, C Wei, N Richardson, CA Hoffman, S Ferris, T AF Rao, Sandhya K. Thompson, Ryan Milford, Creagh Wei, Nancy Richardson, Calvin A. Hoffman, Sara Ferris, Timothy TI ACTIVE REFERRAL MANAGEMENT - A SPECIALIST/PCP COLLABORATION TO ADDRESS ACCESS, VALUE, AND EXPERIENCE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Rao, Sandhya K.; Thompson, Ryan; Milford, Creagh; Wei, Nancy; Ferris, Timothy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richardson, Calvin A.; Hoffman, Sara] Massachusetts Gen Phys Org, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S476 EP S477 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203020 ER PT J AU Reddy, SM Ramachandran, A Cabral, H Kazis, L AF Reddy, Shivani M. Ramachandran, Ambili Cabral, Howard Kazis, Lewis TI PROVISION OF FAMILY PLANNING TO WOMEN WITH CARDIOVASCULAR RISK FACTORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Reddy, Shivani M.; Ramachandran, Ambili] Boston Univ, Sch Med, Boston, MA 02118 USA. [Reddy, Shivani M.] VA Boston Healthcare, Boston, MA USA. [Cabral, Howard; Kazis, Lewis] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S187 EP S188 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201075 ER PT J AU Reddy, SM Quintiliani, L Bowen, DJ AF Reddy, Shivani M. Quintiliani, Lisa Bowen, Deborah J. TI INFORMATION AND COMMUNICATION MEDIA USE BY FEMALE RESIDENTS OF PUBLIC HOUSING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Reddy, Shivani M.; Quintiliani, Lisa] Boston Univ, Sch Med, Boston, MA 02118 USA. [Reddy, Shivani M.] VA Boston Healthcare, Boston, MA USA. [Quintiliani, Lisa; Bowen, Deborah J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S127 EP S127 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200300 ER PT J AU Roy, PJ Kartha, A AF Roy, Payel J. Kartha, Anand TI SEEING THINGS - AN UNUSUAL CAUSE OF VISUAL HALLUCINATIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Roy, Payel J.] Boston Univ, Med Ctr, Boston, MA USA. [Kartha, Anand] VA Boston Healthcare Syst, West Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S429 EP S429 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202331 ER PT J AU Saha, S Gatchell, MS O'Neil, M Bates, JT Gordon, HS Long, JA Washington, DI Gerrity, M AF Saha, Somnath Gatchell, Melissa S. O'Neil, Maya Bates, Jeffrey T. Gordon, Howard S. Long, Judith A. Washington, Donna I. Gerrity, Martha TI PROVIDER CULTURAL COMPETENCE AND RACIAL DISPARITY IN DOCTOR-PATIENT RELATIONSHIPS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Saha, Somnath; Gatchell, Melissa S.; O'Neil, Maya; Gerrity, Martha] Portland VA Med Ctr, Portland, OR USA. [Bates, Jeffrey T.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Gordon, Howard S.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Long, Judith A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Washington, Donna I.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S186 EP S186 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201072 ER PT J AU Schwartz, MD Rose, D Bennett, K Yano, EM AF Schwartz, Mark D. Rose, Danielle Bennett, Katelyn Yano, Elizabeth M. TI THE CHAOTIC PRACTICE ENVIRONMENT IN VA PRIMARY CARE CLINICS: :NATIONAL SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Schwartz, Mark D.; Bennett, Katelyn] VA New York Harbor Healthcare Syst, New York, NY USA. [Schwartz, Mark D.; Bennett, Katelyn] NYU Sch Med, New York, NY USA. [Rose, Danielle] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S221 EP S222 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201155 ER PT J AU Shah, SI Hong, CS Cronin, PR Bearnot, BI Richardson, CA Fosburgh, BW Kimball, A AF Shah, Sachin I. Hong, Clemens S. Cronin, Patrick R. Bearnot, Benjamin I. Richardson, Calvin A. Fosburgh, Blair W. Kimball, Alexandra TI EFFECTIVENESS OF TARGETED PHONE CALLS TO REDUCE NO-SHOWS IN A HOSPITAL-BASED PRIMARY CARE CLINIC: A RANDOMIZED CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Shah, Sachin I.; Hong, Clemens S.; Cronin, Patrick R.; Bearnot, Benjamin I.; Richardson, Calvin A.; Fosburgh, Blair W.; Kimball, Alexandra] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S80 EP S81 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200197 ER PT J AU Sheffrin, M Miao, YH Boscardin, WJ Steinman, MA AF Sheffrin, Meera Miao, Yinghui Boscardin, W. John Steinman, Michael A. TI WEIGHT LOSS ASSOCIATED WITH CHOLINESTERASE INHIBITORS IN PATIENTS WITH DEMENTIA IN A NATIONAL HEALTHCARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 UCSF, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S253 EP S253 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201224 ER PT J AU Shunk, RL O'Brien, B Dulay, MH Keene, T Davis, DL Patel, S Bachhuber, M Chou, CL Weaver, K Kim, C O'Brien, L AF Shunk, Rebecca L. O'Brien, Bridget Dulay, Maya H. Keene, Terry Davis, Denise L. Patel, Shalini Bachhuber, Melissa Chou, Calvin L. Weaver, Kristen Kim, Christina O'Brien, Lynn TI TEACHING INTERPROFESSIONAL TRAINEES TO WORK IN CLINICAL CARE TEAMS: THE SAN FRANCISCO VA CENTER OF EXCELLENCE IN PRIMARY CARE EDUCATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Shunk, Rebecca L.; O'Brien, Bridget; Dulay, Maya H.; Keene, Terry; Davis, Denise L.; Patel, Shalini; Bachhuber, Melissa; Chou, Calvin L.; Weaver, Kristen; Kim, Christina; O'Brien, Lynn] UCSF, San Francisco, CA USA. [Shunk, Rebecca L.; Dulay, Maya H.; Keene, Terry; Davis, Denise L.; Patel, Shalini; Bachhuber, Melissa; Chou, Calvin L.; Weaver, Kristen; Kim, Christina; O'Brien, Lynn] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S535 EP S535 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203154 ER PT J AU Silverman, JB Krieger, J Kiefer, MM Hebert, P Drain, N Robinson, J Taylor, L Kapp, J Nelson, KM AF Silverman, Julie B. Krieger, Jim Kiefer, Meghan M. Hebert, Paul Drain, Nathan Robinson, June Taylor, Leslie Kapp, Janet Nelson, Karin M. TI THE ASSOCIATION OF FOOD INSECURITY AND DIABETES CONTROL AMONG LOW-INCOME INDIVIDUALS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Silverman, Julie B.; Kiefer, Meghan M.; Hebert, Paul; Nelson, Karin M.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Silverman, Julie B.; Krieger, Jim; Kiefer, Meghan M.; Hebert, Paul; Nelson, Karin M.] Univ Washington, Seattle, WA 98195 USA. [Krieger, Jim; Drain, Nathan; Robinson, June; Taylor, Leslie; Kapp, Janet] Seattle King Cty Publ Hlth, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S220 EP S220 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201152 ER PT J AU Simmons, LH Leavitt, L Ray, A Fosburgh, BW Sepucha, KR AF Simmons, Leigh H. Leavitt, Lauren Ray, Alaka Fosburgh, Blair W. Sepucha, Karen R. TI SHARED DECISION MAKING IN CHRONIC CONDITIONS: A CURRICULUM IN USING DECISION AIDS FOR INTERNAL MEDICINE RESIDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Simmons, Leigh H.; Leavitt, Lauren; Ray, Alaka; Fosburgh, Blair W.; Sepucha, Karen R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S533 EP S533 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203150 ER PT J AU Simmons, LH Feibelmann, S Sepucha, KR Leavitt, L AF Simmons, Leigh H. Feibelmann, Sandra Sepucha, Karen R. Leavitt, Lauren TI USE OF A PATIENT DECISION AID IN ROUTINE CARE: WHAT IMPACT DOES IT HAVE ON DECISION MAKING ABOUT PROSTATE CANCER SCREENING? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Simmons, Leigh H.; Feibelmann, Sandra; Sepucha, Karen R.; Leavitt, Lauren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Simmons, Leigh H.; Sepucha, Karen R.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S243 EP S244 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201204 ER PT J AU Simon, B Leykum, L O'Rorke, JE Freeman, M AF Simon, Bret Leykum, Luci O'Rorke, Jane E. Freeman, Megan TI USING COLLABORATIVE EVALUATION TO IDENTIFY CRITERIA FOR THE ASSESSMENT OF ATTENDING PHYSICIANS IN HOSPITAL MEDICINE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Simon, Bret; Leykum, Luci; O'Rorke, Jane E.; Freeman, Megan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Leykum, Luci; O'Rorke, Jane E.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S541 EP S541 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203168 ER PT J AU Simon, B Moreland, C Kornsawad, K AF Simon, Bret Moreland, Christopher Kornsawad, Kanapa TI THE RESIDENT AS TEACHER: IMPLEMENTATION OF AN EVIDENCE-BASED, BEST-PRACTICES APPROACH TO CLINICAL EDUCATION THROUGH A TEACHING ELECTIVE FOR RESIDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Simon, Bret; Moreland, Christopher; Kornsawad, Kanapa] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Moreland, Christopher; Kornsawad, Kanapa] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S539 EP S540 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203165 ER PT J AU Simonetti, J Rowhani-Rahbar, A Zatzick, D Young, B Rivara, F AF Simonetti, Joseph Rowhani-Rahbar, Ali Zatzick, Douglas Young, Bessie Rivara, Frederick TI STATE FIREARM LEGISLATION AND NONFATAL FIREARM INJURIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Simonetti, Joseph; Rowhani-Rahbar, Ali; Zatzick, Douglas; Rivara, Frederick] Univ Washington, Seattle, WA 98195 USA. [Simonetti, Joseph; Rowhani-Rahbar, Ali; Young, Bessie] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Young, Bessie] VA Puget Sound, Northwest Ctr Excellence, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S210 EP S210 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201128 ER PT J AU Simonetti, J Lapham, GT Williams, E AF Simonetti, Joseph Lapham, Gwen T. Williams, Emily TI RECEIPT OF ALCOHOL-RELATED ADVICE AND QUALITY OF CARE AMONG VETERAN OUTPATIENTS WITH UNHEALTHY ALCOHOL USE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Simonetti, Joseph; Williams, Emily] Univ Washington, Seattle, WA 98195 USA. [Lapham, Gwen T.; Williams, Emily] VA Puget Sound, Seattle Denver HSR&D COIN, Seattle, WA 98195 USA. [Lapham, Gwen T.] Grp Hlth Res Inst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S194 EP S194 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201091 ER PT J AU Slight, SP Seger, DL Nanji, KC Cho, I Maniam, N Dkyes, PC Bates, DW AF Slight, Sarah P. Seger, Diane L. Nanji, Karen C. Cho, Insook Maniam, Nivethietha Dkyes, Patricia C. Bates, David W. TI AN EVALUATION OF COMPUTERIZED DRUG-DRUG INTERACTION ALERT OVERRIDES IN AMBULATORY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Slight, Sarah P.; Cho, Insook; Dkyes, Patricia C.; Bates, David W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Slight, Sarah P.] Univ Durham, Stockton On Tees, England. [Seger, Diane L.; Maniam, Nivethietha] Partners Healthcare Syst Inc, Boston, MA USA. [Nanji, Karen C.; Dkyes, Patricia C.; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Nanji, Karen C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cho, Insook] Inha Univ, Incheon, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S20 EP S20 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200050 ER PT J AU Sue, K Hubbeling, H Kuo, C Brubaker, K Xu, LY Fernandez-Golarz, C Cohen, MJ Keuroghlian, A AF Sue, Kimberly Hubbeling, Harper Kuo, Christine Brubaker, Katy Xu, Luyi Fernandez-Golarz, Carina Cohen, Marya J. Keuroghlian, Alex TI POST-PRISON BLUES: UTILIZING A PRIMARY CARE STUDENT-FACULTY COLLABORATIVE CLINIC TO CONCURRENTLY TREAT HEROIN ADDICTION, PTSD AND HEPATITIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Sue, Kimberly; Hubbeling, Harper; Kuo, Christine; Brubaker, Katy; Xu, Luyi; Fernandez-Golarz, Carina; Cohen, Marya J.] Harvard Univ, Sch Med, MGH Chelsea, Chelsea, MA USA. [Keuroghlian, Alex] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S411 EP S411 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202279 ER PT J AU Sugiyama, T Hasegawa, K Takahashi, O Fukui, T Tsugawa, Y AF Sugiyama, Takehiro Hasegawa, Kohei Takahashi, Osamu Fukui, Tsuguya Tsugawa, Yusuke TI TIME TRENDS OF CLINICAL OUTCOME AND SPENDING OF CARE FOR ACUTE MYOCARDIAL INFARCTION HOSPITALIZATIONS IN THE UNITED STATES, 2001-2011 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Sugiyama, Takehiro] Univ Tokyo, Tokyo, Japan. [Sugiyama, Takehiro] Natl Ctr Global Hlth & Med, Tokyo, Japan. [Hasegawa, Kohei] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hasegawa, Kohei] Harvard Univ, Sch Med, Boston, MA USA. [Takahashi, Osamu; Fukui, Tsuguya] St Lukes Int Hosp, Tokyo, Japan. [Tsugawa, Yusuke] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S237 EP S237 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201189 ER PT J AU Sylling, PW Wong, E Liu, CF Hernandez, S Batten, A Helfrich, C Nelson, KM Fihn, SD Hebert, P AF Sylling, Philip W. Wong, Edwin Liu, Chuan-Fen Hernandez, Susan Batten, Adam Helfrich, Christian Nelson, Karin M. Fihn, Stephan D. Hebert, Paul TI PATIENT-CENTERED MEDICAL HOME IMPLEMENTATION AND PROVIDER JOB TURNOVER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Sylling, Philip W.; Wong, Edwin; Liu, Chuan-Fen; Hernandez, Susan; Batten, Adam; Helfrich, Christian; Nelson, Karin M.; Hebert, Paul] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Fihn, Stephan D.] Univ Washington, Seattle, WA 98195 USA. [Fihn, Stephan D.] Vet Hlth Adm, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S167 EP S168 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201033 ER PT J AU Thomas, HN Evans, GW Berlowitz, D Bonds, DE Chertow, GM Conroy, MB Foy, C Glasser, S Lewis, CE Riley, WT Russell, L Williams, O Hess, R AF Thomas, Holly N. Evans, Gregory W. Berlowitz, Dan Bonds, Denise E. Chertow, Glenn M. Conroy, Molly B. Foy, Capri Glasser, Stephen Lewis, Cora E. Riley, William T. Russell, Laurie Williams, Olubunmi Hess, Rachel TI THE RELATION BETWEEN ANTIHYPERTENSIVE MEDICATION AND SEXUAL FUNCTION IN WOMEN: BASELINE DATA FROM THE SPRINT STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Thomas, Holly N.; Conroy, Molly B.; Hess, Rachel] Univ Pittsburgh, Pittsburgh, PA USA. [Thomas, Holly N.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Evans, Gregory W.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Berlowitz, Dan] Bedford VA Hosp, Bedford, MA USA. [Berlowitz, Dan] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bonds, Denise E.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Foy, Capri; Russell, Laurie] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Glasser, Stephen; Lewis, Cora E.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Riley, William T.] NIMH, Bethesda, MD 20892 USA. [Williams, Olubunmi] Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S231 EP S231 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201177 ER PT J AU Thomas, HN Hess, R AF Thomas, Holly N. Hess, Rachel TI CORRELATES OF SEXUAL SATISFACTION IN MIDLIFE WOMEN: COMMUNICATION IS KEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Thomas, Holly N.; Hess, Rachel] Univ Pittsburgh, Pittsburgh, PA USA. [Thomas, Holly N.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S58 EP S59 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200143 ER PT J AU Thompson, R Sikora, C Veo, M Jennings, K Ferris, T AF Thompson, Ryan Sikora, Chrisanne Veo, Maria Jennings, Keith Ferris, Timothy TI CONTINUITY VISITS - A MODEL TO IMPROVE RELATIONAL CONTINUITY BETWEEN PATIENTS AND THEIR LONGITUDINAL PHYSICIANS DURING ACUTE HOSPITAL ADMISSIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Thompson, Ryan; Sikora, Chrisanne; Veo, Maria; Jennings, Keith; Ferris, Timothy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S57 EP S57 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200140 ER PT J AU Ueno, R Maeda, A Nagasaka, M Lam, WL Karter, D Perlman, DC AF Ueno, Rie Maeda, Ayumi Nagasaka, Misako Lam, Wan L. Karter, Dennis Perlman, David C. TI DISSEMINATED PYOGENIC INFECTION CAUSED BY STREPTOCOCCUS ANGINOSUS THROUGH HEMATOGENOUS SPREAD VIA INFECTIOUS ENDOCARDITIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Ueno, Rie; Nagasaka, Misako; Lam, Wan L.; Karter, Dennis; Perlman, David C.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Maeda, Ayumi] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S346 EP S347 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996202095 ER PT J AU Vassy, JL Christensen, KD Slashinski, MJ Lautenbach, D Robinson, JO Blumenthal-Barby, JA Feuerman, L Green, RC McGuire, AL AF Vassy, Jason L. Christensen, Kurt D. Slashinski, Melody J. Lautenbach, Denise Robinson, Jill Oliver Blumenthal-Barby, Jennifer A. Feuerman, Lindsay Green, Robert C. McGuire, Amy L. TI "SOMEDAY IT WILL BE THE NORM": PHYSICIAN PERCEPTIONS OF THE CLINICAL UTILITY: OF WHOLE GENOME SEQUENCING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Vassy, Jason L.] VA Boston Healthcare Syst, Boston, MA USA. [Vassy, Jason L.; Christensen, Kurt D.; Lautenbach, Denise; Green, Robert C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Slashinski, Melody J.; Robinson, Jill Oliver; Blumenthal-Barby, Jennifer A.; Feuerman, Lindsay; McGuire, Amy L.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S4 EP S4 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200010 ER PT J AU Vimalananda, V Gupte, G Clark, J Orlander, JD Simon, SR AF Vimalananda, Varsha Gupte, Gouri Clark, Justice Orlander, Jay D. Simon, Steven R. TI ADOPTION AND UTILIZATION OF E-CONSULTS IN A VETERANS AFFAIRS HEALTHCARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Vimalananda, Varsha] CHOIR, Bedford, MA USA. [Clark, Justice; Orlander, Jay D.; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Gupte, Gouri] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S477 EP S478 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203022 ER PT J AU Wachterman, MW McCarthy, EP Marcantonio, ER Ersek, M AF Wachterman, Melissa W. McCarthy, Ellen P. Marcantonio, Edward R. Ersek, Mary TI MISTRUST, MISPERCEPTIONS, AND MISCOMMUNICATION: A QUALITATIVE STUDY OF PREFERENCES ABOUT KIDNEY TRANSPLANTATION AMONG AFRICAN-AMERICANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Wachterman, Melissa W.] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Wachterman, Melissa W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [McCarthy, Ellen P.; Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [McCarthy, Ellen P.] Harvard Univ, Sch Med, Boston, MA USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Ersek, Mary] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S151 EP S152 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200353 ER PT J AU Wakeman, SE Pham-Kanter, G Baggett, M Campbell, E AF Wakeman, Sarah E. Pham-Kanter, Genevieve Baggett, Meridale Campbell, Eric TI IMPROVING INTERNAL MEDICINE RESIDENT PREPAREDNESS TO DIAGNOSE AND TREAT SUBSTANCE USE DISORDERS; EVALUATING THE IMPACT OF AN ENHANCED ADDICTION CURRICULUM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Wakeman, Sarah E.; Baggett, Meridale; Campbell, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pham-Kanter, Genevieve] Univ Colorado, Denver, CO 80202 USA. [Campbell, Eric] Mongan Inst Hlth Policy, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S124 EP S124 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200294 ER PT J AU Walling, AM Tisnado, D Ettner, S Asch, S Dy, SM Pantoja, P Lee, M Ahluwalia, S Schreibeis-Baum, HC Lorenz, K AF Walling, Anne M. Tisnado, Diana Ettner, Susan Asch, Steven Dy, Sydney M. Pantoja, Philip Lee, Martin Ahluwalia, Sangeeta Schreibeis-Baum, Hannah C. Lorenz, Karl TI EARLY PALLIATIVE CARE CONSULTATION IS ASSOCIATED WITH IMPROVED SUPPORTIVE CARE CANCER QUALITY FOR VETERANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Walling, Anne M.; Ettner, Susan] Univ Calif Los Angeles, Los Angeles, CA USA. [Walling, Anne M.; Tisnado, Diana; Pantoja, Philip; Lee, Martin; Schreibeis-Baum, Hannah C.; Lorenz, Karl] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ahluwalia, Sangeeta] Oregon State Univ, Corvallis, OR 97331 USA. [Asch, Steven] VA Palo Alto, Palo Alto, CA USA. [Dy, Sydney M.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S77 EP S77 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200188 ER PT J AU Washington, DI Danz, M Cordasco, KM AF Washington, Donna I. Danz, Marjorie Cordasco, Kristina M. TI DEVELOPMENT OF QUALITY INDICATORS FOR THE CARE OF WOMEN WITH ABNORMAL UTERINE BLEEDING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Washington, Donna I.; Danz, Marjorie; Cordasco, Kristina M.] VA Greater Los Angeles Healthcare, Los Angeles, CA USA. [Washington, Donna I.; Cordasco, Kristina M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Danz, Marjorie] RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S68 EP S69 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200169 ER PT J AU Woodard, LD Virani, SS Petersen, LA Amspoker, A Urecht, T Ramsey, D Adepoju, OE Mehta, P Murawsky, JA Naik, AD AF Woodard, LeChauncy D. Virani, Salim S. Petersen, Laura A. Amspoker, Amber Urecht, Tracy Ramsey, David Adepoju, Omolola E. Mehta, Praveen Murawsky, Jeffrey A. Naik, Aanand D. TI DISPARITIES IN GLYCEMIC AND LIPID CONTROL AMONG DIABETIC PATIENTS IN THE VETERANS ADMINISTRATION: IMPLICATIONS IN THE ERA OF THE AFFORDABLE CARE ACT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Woodard, LeChauncy D.; Virani, Salim S.; Petersen, Laura A.; Amspoker, Amber; Urecht, Tracy; Ramsey, David; Adepoju, Omolola E.; Naik, Aanand D.] Michael E DeBakey Med Ctr, HSR&D, Houston, TX USA. [Mehta, Praveen; Murawsky, Jeffrey A.] VISN 12 Great Lakes, Westchester, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S73 EP S73 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200180 ER PT J AU Yeh, J Austad, K Franklin, JM Chimonas, S Campbell, E Avorn, J Kesselheim, A AF Yeh, James Austad, Kirsten Franklin, Jessica M. Chimonas, Susan Campbell, Eric Avorn, Jerry Kesselheim, Aaron TI STRONG MEDICAL SCHOOL INDUSTRY INTERACTION POLICIES HAVE NO PROTECTIVE EFFECT ON STUDENTS' BEHAVIOR AS RESIDENTS: RESULTS OF A NATIONAL SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Yeh, James; Austad, Kirsten; Franklin, Jessica M.; Avorn, Jerry; Kesselheim, Aaron] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeh, James; Austad, Kirsten; Franklin, Jessica M.; Campbell, Eric; Avorn, Jerry; Kesselheim, Aaron] Harvard Univ, Sch Med, Boston, MA USA. [Chimonas, Susan] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Campbell, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S211 EP S212 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996201131 ER PT J AU Yeh, J Austad, K Franklin, J Chimonas, S Campbell, E Avorn, J Kesselheim, A AF Yeh, James Austad, Kirsten Franklin, Jessica Chimonas, Susan Campbell, Eric Avorn, Jerry Kesselheim, Aaron TI INSTITUTIONAL PREDICTORS OF MEDICAL STUDENTS' INTERACTIONS WITH THE PHARMACEUTICAL AND MEDICAL DEVICE INDUSTRIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Yeh, James; Austad, Kirsten; Franklin, Jessica; Avorn, Jerry; Kesselheim, Aaron] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeh, James; Austad, Kirsten; Franklin, Jessica; Campbell, Eric; Avorn, Jerry; Kesselheim, Aaron] Harvard Univ, Sch Med, Boston, MA USA. [Chimonas, Susan] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Campbell, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S127 EP S128 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200302 ER PT J AU Yelibi, C Ward, CE Chang, YC Ashburner, JM Hong, CS Atlas, SJ AF Yelibi, Carine Ward, Charlotte E. Chang, Yuchiao Ashburner, Jeffrey M. Hong, Clemens S. Atlas, Steven J. TI DO PRIMARY CARE PHYSICIANS WHO DELIVER BETTER QUALITY OF CARE ALSO USE LESS HEALTH CARE RESOURCES? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Yelibi, Carine; Ward, Charlotte E.; Chang, Yuchiao; Ashburner, Jeffrey M.; Hong, Clemens S.; Atlas, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S75 EP S75 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200184 ER PT J AU Young, EA Paulk, J Beck, JM Anderson, M Burck, M Szapor, S Roberts, A Stickrath, C AF Young, Eric A. Paulk, Jaime Beck, James M. Anderson, Mel Burck, McKenna Szapor, Stephen Roberts, Adam Stickrath, Chad TI A UNIQUE MODEL FOR MULTIDISCIPLINARY BEDSIDE ROUNDS IN AN ACADEMIC TEACHLNG HOSPITAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Young, Eric A.; Paulk, Jaime; Beck, James M.; Anderson, Mel; Burck, McKenna; Szapor, Stephen; Roberts, Adam; Stickrath, Chad] Denver VA Med Ctr, Denver, CO USA. [Young, Eric A.; Beck, James M.; Anderson, Mel; Stickrath, Chad] Univ Colorado, Sch Med, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S476 EP S476 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996203019 ER PT J AU Zuchowski, J Hamilton, AB Washington, DL Cordasco, KM AF Zuchowski, Jessica Hamilton, Alison B. Washington, Donna L. Cordasco, Kristina M. TI LEARNING NEEDS OF VHA WOMEN'S HEALTH PROVIDERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-General-Internal-Medicine CY APR 23-26, 2014 CL San Diego, CA SP Soc Gen Internal Med C1 [Zuchowski, Jessica; Hamilton, Alison B.; Washington, Donna L.; Cordasco, Kristina M.] US Dept Vet Affairs, North Hills, CA USA. [Hamilton, Alison B.; Washington, Donna L.; Cordasco, Kristina M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2014 VL 29 SU 1 BP S138 EP S139 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO0JZ UT WOS:000340996200327 ER PT J AU Glassm, PA Schneider, PL Good, CB AF Glassm, Peter A. Schneider, Paul L. Good, Chester B. TI An Ethical Framework for Pharmacy Management: Balancing Autonomy and Other Principles SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Editorial Material ID AMERICAN-COLLEGE; 6TH EDITION; CARE AB Decisions to control pharmaceutical costs can cause conflicts as to what medications are covered. Such conflicts have ethical implications, however implicit, and given this fact, an ethical framework can help address them In the following commentary, we discuss the more traditional, individual-level ethical considerations likely familiar to most clinicians. We, then, discuss population-level ethical constructs that clinicians may not as readily embrace. We also present a hypothetical cancer-care case to illustrate how imbalances in ethical foci between individual- and population-level constructs may lead to conflicts among health care actors and promote shifts in pharmaceutical decision making away from providers and toward payers, paradoxically reducing provider autonomy and hence patient autonomy. Finally, we propose a more comprehensive ethical framework to help converge individual, payer, and societal interests when making pharmaceutical use decisions. Pharmacists play a crucial role as pharmacy benefits managers and should be familiar with individual- and population-based ethical constructs. Copyright (C) 2014, Academy of Managed Care Pharmacy. All rights reserved. C1 [Glassm, Peter A.] VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. [Glassm, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Schneider, Paul L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Schneider, Paul L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Good, Chester B.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Pittsburgh, PA USA. RP Glassm, PA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, 11301 Wilshire Blvd,Mail Stop 111G, Los Angeles, CA 90073 USA. EM peter.glassman@va.gov NR 26 TC 0 Z9 1 U1 0 U2 0 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAGE CARE PHARM JI J. Manag. Care Pharm. PD APR PY 2014 VL 20 IS 4 BP 334 EP 338 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA AO5RO UT WOS:000341403200001 PM 24684637 ER PT J AU Lutwak, N Byne, W AF Lutwak, Nancy Byne, William TI Deployment-Related Risk Factors of Low Back Pain: A Study Among Danish Soldiers Deployed to Iraq SO MILITARY MEDICINE LA English DT Letter C1 [Lutwak, Nancy] VA New York Harbor Healthcare Syst, New York, NY USA. [Byne, William] James J Peters VA Med Ctr, New York, NY USA. RP Lutwak, N (reprint author), VA New York Harbor Healthcare Syst, Manhattan Campus, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD APR PY 2014 VL 179 IS 4 BP VIII EP IX PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AN7UK UT WOS:000340806300019 ER PT J AU Ament, SA Earls, J Grindeland, A St Claire, J Gillis, T O'Moore, J Duong, H Guide, J Cassen, V Mysore, L Troisch, P Kovalenko, M Guide, J Cho, JH Lee, I Howland, D Kwak, S Carroll, J Gusella, J MacDonald, M Lee, JM Geman, D Wheeler, V Price, N Goodman, N Hood, L Carlson, GA AF Ament, Seth A. Earls, John Grindeland, Andrea St Claire, Jason Gillis, Tammy O'Moore, Jill Duong, Hien Guide, Jolene Cassen, Victor Mysore, Lakshmi Troisch, Pam Kovalenko, Marina Guide, Jolene Cho, Ji-Hoon Lee, Inyoul Howland, David Kwak, Seung Carroll, Jeff Gusella, Jim MacDonald, Marcy Lee, Jong Min Geman, Don Wheeler, Vanessa Price, Nathan Goodman, Nat Hood, Lee Carlson, George A. TI Comparison of dynamic perturbed networks in mouse models of Huntington's disease and prion infection SO PRION LA English DT Meeting Abstract C1 [Ament, Seth A.; Earls, John; Duong, Hien; Cassen, Victor; Troisch, Pam; Cho, Ji-Hoon; Lee, Inyoul; Price, Nathan; Goodman, Nat; Hood, Lee] Inst Syst Biol, Seattle, WA USA. [Grindeland, Andrea; O'Moore, Jill; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT USA. [St Claire, Jason; Gillis, Tammy; Guide, Jolene; Mysore, Lakshmi; Kovalenko, Marina; Guide, Jolene; Gusella, Jim; MacDonald, Marcy; Lee, Jong Min; Wheeler, Vanessa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Howland, David; Kwak, Seung] CHDI Fdn, Princeton, NJ USA. [Carroll, Jeff] Western Washington Univ, Bellingham, WA 98225 USA. [Geman, Don] Johns Hopkins Univ, Baltimore, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.176 BP 108 EP 108 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900231 ER PT J AU Minikel, E Vallabh, S Lek, M MacArthur, DG AF Minikel, Eric Vallabh, Sonia Lek, Monkol MacArthur, Daniel G. CA ExAC TI Prion protein genetic variation in 50,000 humans SO PRION LA English DT Meeting Abstract DE genetics; PrP C1 [Minikel, Eric; Vallabh, Sonia] Pr Alliance, Cambridge, MA USA. [Minikel, Eric; Lek, Monkol; MacArthur, Daniel G.] Broad Inst, Cambridge, MA USA. [Minikel, Eric; Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Vallabh, Sonia] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2014 VL 8 SU S MA P.191 BP 115 EP 116 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AN5FD UT WOS:000340614900246 ER PT J AU Provias, T Weinberg, I Schainfeld, R Jaff, M AF Provias, Tim Weinberg, Ido Schainfeld, Robert Jaff, Michael TI Inferior vena cava compression by a hematoma SO VASCULAR MEDICINE LA English DT Editorial Material C1 [Provias, Tim; Weinberg, Ido; Schainfeld, Robert; Jaff, Michael] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Div Cardiol, Boston, MA 02114 USA. RP Provias, T (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM tprovias@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD APR PY 2014 VL 19 IS 2 BP 146 EP 147 DI 10.1177/1358863X14524615 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AM8XI UT WOS:000340162100012 PM 24595326 ER PT J AU Dranoff, G AF Dranoff, Glenn TI Cancer Immunology Essentials: A Prefac0e SO CANCER IMMUNOLOGY RESEARCH LA English DT Editorial Material C1 [Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. RP Dranoff, G (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD APR PY 2014 VL 2 IS 4 BP 287 EP 287 DI 10.1158/2326-6066.CIR-14-0043 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA AM7GO UT WOS:000340033600001 PM 24764574 ER PT J AU Chiocca, EA Rabkin, SD AF Chiocca, E. Antonio Rabkin, Samuel D. TI Oncolytic Viruses and Their Application to Cancer Immunotherapy SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID HERPES-SIMPLEX-VIRUS; VESICULAR STOMATITIS-VIRUS; GM-CSF; ANTITUMOR EFFICACY; IMMUNE-RESPONSES; VIRAL ONCOLYSIS; CDNA LIBRARIES; VIROTHERAPY; ADENOVIRUS; MELANOMA AB Oncolytic viruses (OV) selectively replicate and kill cancer cells and spread within the tumor, while not harming normal tissue. In addition to this direct oncolytic activity, OVs are also very effective at inducing immune responses to themselves and to the infected tumor cells. OVs encompass a broad diversity of DNA and RNA viruses that are naturally cancer selective or can be genetically engineered. OVs provide a diverse platform for immunotherapy; they act as in situ vaccines and can be armed with immunomodulatory transgenes or combined with other immunotherapies. However, the interactions of OVs with the immune system may affect therapeutic outcomes in opposing fashions: negatively by limiting virus replication and/or spread, or positively by inducing antitumor immune responses. Many aspects of the OV-tumor/host interaction are important in delineating the effectiveness of therapy: (i) innate immune responses and the degree of inflammation induced; (ii) types of virus-induced cell death; (iii) inherent tumor physiology, such as infiltrating and resident immune cells, vascularity/hypoxia, lymphatics, and stromal architecture; and (iv) tumor cell phenotype, including alterations in IFN signaling, oncogenic pathways, cell surface immune markers [MHC, costimulatory, and natural killer (NK) receptors], and the expression of immunosuppressive factors. Recent clinical trials with a variety of OVs, especially those expressing granulocyte macrophage colony-stimulating factor (GM-CSF), have demonstrated efficacy and induction of antitumor immune responses in the absence of significant toxicity. Manipulating the balance between antivirus and antitumor responses, often involving overlapping immune pathways, will be critical to the clinical success of OVs. (C)2014 AACR. C1 [Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Rabkin, Samuel D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. RP Chiocca, EA (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 3rd Floor,75 Francis St, Boston, MA 02115 USA. EM EACHIOCCA@PARTNERS.ORG FU NIH [R01CA160762, P01CA163205, P01CA069246, R01CA166172, U01NS061811]; Thomas A. Pappas Chair in Neurosciences FX S.D. Rabkin is funded by the NIH, grant no. R01CA160762 and the Thomas A. Pappas Chair in Neurosciences. E.A. Chiocca is funded by the NIH, grant nos. P01CA163205, P01CA069246, R01CA166172, and U01NS061811. NR 55 TC 52 Z9 53 U1 8 U2 27 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD APR PY 2014 VL 2 IS 4 BP 295 EP 300 DI 10.1158/2326-6066.CIR-14-0015 PG 6 WC Oncology; Immunology SC Oncology; Immunology GA AM7GO UT WOS:000340033600003 PM 24764576 ER PT J AU Lipinski, B AF Lipinski, Boguslaw TI Iron-induced parafibrin formation in tumors fosters immune evasion SO ONCOIMMUNOLOGY LA English DT Article DE fibrinogen; hydrophobic bonds; iron; NK cells; parafibrin; polyphenols ID BREAST-CANCER; MEDITERRANEAN DIET; FIBRINOGEN; DISEASE; CELLS; RISK; TRIAL AB Although efficacious in vitro, it is well known that adoptive immunotherapeutic modalities lose their potency when applied in vivo. Furthermore, malignant cell exposure to blood platelets attenuates the anticancer activity of natural killer (NK) cells. We argue that upon contact with redox iron, fibrinogen is converted to a hydrophobic fibrin-like polymer that coats tumor cells and provides protection from immune-mediated destruction. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Lipinski, B (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM b.lipinski2006@rcn.com NR 30 TC 1 Z9 1 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR PY 2014 VL 3 IS 4 AR e28539 DI 10.4161/onci.28539 PG 4 WC Oncology; Immunology SC Oncology; Immunology GA AM6EL UT WOS:000339955700023 ER PT J AU Zhou, PH Wucherpfennig, KW AF Zhou, Penghui Wucherpfennig, Kai W. TI Discovering cancer immunotherapy targets in vivo SO ONCOIMMUNOLOGY LA English DT Editorial Material DE cancer; T cell; therapeutic targets; RNAi screen; tumor microenvironment ID ANTIBODY; SAFETY; CELLS AB A key challenge facing the cancer immunology field is the discovery of the most suitable targets for therapeutic intervention. We recently reported a novel RNA-interference (RNAi)-based approach for systematic discovery of such targets in the tumor microenvironment in vivo utilizing pooled shRNA libraries as a screening tool. Here, we discuss applying this unbiased method to develop innovative cancer therapeutics. C1 [Zhou, Penghui; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu NR 10 TC 1 Z9 1 U1 1 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR PY 2014 VL 3 IS 4 AR e28500 DI 10.4161/onci.28500 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA AM6EL UT WOS:000339955700021 ER PT J AU Loureiro, J Oliva, E AF Loureiro, Joana Oliva, Esther TI The Spectrum of Cervical Glandular Neoplasia and Issues in Differential Diagnosis SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ADENOCARCINOMA IN-SITU; MINIMAL-DEVIATION ADENOCARCINOMA; FEMALE GENITAL-TRACT; CLEAR-CELL ADENOCARCINOMA; PEUTZ-JEGHERS-SYNDROME; ARIAS-STELLA REACTION; SIGNET-RING CELL; HUMAN-PAPILLOMAVIRUS INFECTION; EARLY INVASIVE ADENOCARCINOMA; VILLOGLANDULAR PAPILLARY ADENOCARCINOMA AB Context.-Premalignant and malignant glandular lesions of the cervix are known to often cause diagnostic problems with a variety of benign (more common) as well as other malignant mimics, the latter setting often being represented by secondary involvement by endometrioid endometrial carcinoma especially in small samplings. Objectives.-To highlight key histologic features and immunohistochemical markers that may be helpful in the distinction of in situ endocervical carcinoma from benign glandular proliferations, and those that separate different subtypes of invasive endocervical carcinoma, as well as invasive carcinoma from other carcinomas secondarily involving the cervix and nonneoplastic proliferations of the cervix. Conclusions.-Clinical and morphologic features as well as immunohistochemistry results should be used in conjunction in the differential diagnosis of glandular proliferations of the cervix, as correct interpretation has major clinical consequences for the patient in most instances (especially benign versus malignant). Immunohistochemical markers should be used as part of a panel of antibodies, as exceptions may occur to the usual pattern of staining, and if used singly, they may mislead the pathologist to establish a wrong diagnosis. C1 [Loureiro, Joana] Inst Portugues Oncol Francisco Gentil, Dept Pathol, Oporto, Portugal. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org NR 313 TC 13 Z9 13 U1 0 U2 5 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2014 VL 138 IS 4 BP 453 EP 483 DI 10.5858/arpa.2012-0493-RA PG 31 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AM0QY UT WOS:000339552200002 PM 24678677 ER PT J AU Zhang, W McQuitty, EB Olsen, R Fan, HX Hendrickson, H Tio, FO Newton, K Cagle, PT Jagirdar, J AF Zhang, Wei McQuitty, Elizabeth B. Olsen, Randall Fan, Hongxin Hendrickson, Heather Tio, Fermin O. Newton, Keith Cagle, Philip T. Jagirdar, Jaishree TI EGFR Mutations in US Hispanic Versus Non-Hispanic White Patients With Lung Adenocarcinoma SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID FACTOR RECEPTOR MUTATIONS; ADJUVANT CHEMOTHERAPY; CANCER; GEFITINIB; RESISTANCE; FUTURE AB Context.-Lung cancer is the leading cause of cancer deaths worldwide. First-generation tyrosine kinase inhibitors improve progression-free survival in lung cancers with epidermal growth factor receptor (EGFR) mutations. EGFR mutations occur predominantly in exons 19 and 21 in lung adenocarcinomas of Asians (similar to 30%), whites (similar to 15%), and African Americans (similar to 19%). However, minimal information exists on the prevalence or type of genetic changes that occur in lung cancers in US Hispanic patients. We investigated the EGFR mutation frequency in primary lung adenocarcinomas in US Hispanics compared with non-Hispanic whites. Objective.-To evaluate EGFR mutations in lung adenocarcinomas from US Hispanic patients compared with those from non-Hispanic white patients. Design.-DNA samples were extracted from paraffin-embedded tissue of consecutive lung adenocarcinomas from 83 patients. Samples were collected from 40 Hispanics and 43 non-Hispanic whites. Mutations in EGFR were analyzed using a custom assay. Results.-Fourteen of 83 patients (16.9%) had EGFR mutations in their tumor DNA, including 6 of 40 Hispanics (15.0%) and 8 of 43 non-Hispanic whites (18.6%). No association with age, sex, or tumor stage was identified. Smoking history could not be obtained for most of the 83 patients, although 8 of the 11 patients with EGFR mutations for whom smoking history was obtained were nonsmokers. Most of the tumors with EGFR mutations (12 of 14; 85.7%) were acinar with lepidic or papillary subtypes. EGFR mutations occurred in exon 19 (42.8%), exon 18 (28.6%), exon 20 (28.6%), and exon 21 (14.3%). Two cases had 2 mutations identified in different exons. Conclusion.-The frequency of EGFR mutations is similar in US Hispanics compared with non-Hispanic whites. C1 [Zhang, Wei; Jagirdar, Jaishree] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Fan, Hongxin] Univ Texas Hlth Sci Ctr San Antonio, Mol Diagnost Lab, San Antonio, TX 78229 USA. [Tio, Fermin O.] Audie L Murphy Mem Vet Adm Med Ctr, Lab Serv, San Antonio, TX 78284 USA. [McQuitty, Elizabeth B.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Olsen, Randall; Hendrickson, Heather; Newton, Keith; Cagle, Philip T.] Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA. RP Jagirdar, J (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Mail Code 7750 7703,Floyd Curl Dr, San Antonio, TX 78229 USA. EM Jagirdar@UTHSCSA.edu NR 24 TC 5 Z9 5 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2014 VL 138 IS 4 BP 543 EP 545 DI 10.5858/arpa.2013-0311-OA PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA AM0QY UT WOS:000339552200011 PM 23937608 ER PT J AU Heng, M Kwon, JY AF Heng, Marilyn Kwon, John Y. TI Percutaneous Osteotomy for Irreducible or Malunited Tongue-type Calcaneus Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE trauma; calcaneus fracture; percutaneous fixation; osteotomy; tongue-type AB The optimal treatment of calcaneus fractures remains a much-debated topic. One of the clearer indications for operative treatment has been the presence of a tongue-type fracture pattern with compromise to the posterior soft tissue envelope which necessitates operative urgency. However, at other times the threat to the skin is minor and the urgency to operate is lessened or perhaps negated by issues such as unfavorable soft tissue swelling or unsuitable overall stability of the patient for surgery. Given the continuity of the depressed posterior facet with the calcaneal tuberosity, tongue-type fractures can often be managed using percutaneous reduction and fixation techniques as described by Essex-Lopresti, Tornetta, Forgon and Zadravecz, and others.(1-5,9) Although open extensile approaches can be used as well, percutaneous techniques mitigate potential wound healing complications. However, fracture consolidation increases as time from injury to definitive fixation increases and the use of percutaneous techniques becomes increasingly more difficult if not impossible. Traditionally, open techniques were employed if reduction was not possible using percutaneous techniques or if surgeons felt that considerable fracture consolidation had already occurred. Yu et al, Rammelt et al, and others have described osteotomies of malunited calcaneus fractures utilizing the extensile lateral approach. We present an operative technique for percutaneous osteotomy of irreducible and malunited tongue-type calcaneus fractures that avoids the use of the extensile lateral approach with an illustrative case presentation. C1 [Heng, Marilyn] Univ Toronto, Toronto, ON M5G 1X5, Canada. [Kwon, John Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Heng, M (reprint author), Univ Toronto, Div Orthopaed Surg, 600 Univ Ave,Room 476i, Toronto, ON M5G 1X5, Canada. EM marilyn.heng@mail.utoronto.ca NR 11 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD APR PY 2014 VL 35 IS 4 BP 408 EP 414 DI 10.1177/1071100713517874 PG 7 WC Orthopedics SC Orthopedics GA AL7QD UT WOS:000339328800015 PM 24357678 ER PT J AU Jennelle, L Hunegnaw, R Dubrovsky, L Pushkarsky, T Fitzgerald, ML Sviridov, D Bukrinsky, M AF Jennelle, Lucas Hunegnaw, Ruth Dubrovsky, Larisa Pushkarsky, Tatiana Fitzgerald, Michael L. Sviridov, Dmitri Bukrinsky, Michael TI HIV-1 Nef regulates activity of endoplasmic reticulum chaperone calnexin SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 15th Annual International Meeting of the Institute-of-Human-Virology CY SEP 08-12, 2013 CL Moscow, RUSSIA SP Inst Human Virol, Univ Maryland Sch Med, Inst Human Virol C1 [Jennelle, Lucas; Hunegnaw, Ruth; Dubrovsky, Larisa; Pushkarsky, Tatiana; Bukrinsky, Michael] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. [Fitzgerald, Michael L.] Harvard Univ, Massachusetts Gen Hosp, Lipid Metab Unit, Sch Med, Boston, MA 02114 USA. [Sviridov, Dmitri] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2014 VL 65 SU 2 MA 136 BP 57 EP 57 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL3LD UT WOS:000339028300033 ER PT J AU Cade, F Paschalis, EI Regatieri, CV Vavvas, DG Dana, R Dohlman, CH AF Cade, Fabiano Paschalis, Eleftherios I. Regatieri, Caio V. Vavvas, Demetrios G. Dana, Reza Dohlman, Claes H. TI Alkali Burn to the Eye: Protection Using TNF-alpha Inhibition SO CORNEA LA English DT Article DE inflammation; alkali burn; chemical injury; ganglion cell layer; cornea ID PHOTORECEPTOR DEATH; CHEMICAL INJURY; INFLIXIMAB; NECROSIS; TUMOR; MODEL AB PURPOSE: The aim of this study was to evaluate early retinal damage after induction of ocular surface alkali burns and the protective effects of tumor necrosis factor alpha (TNF-a) blockade. METHODS: Alkali injury was induced in mouse corneas by using 1 N NaOH. Retinal damage was assessed using a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay, 15 minutes to 14 days postburn. Immune cell infiltration was assessed by CD45 immunolocalization. Retinal cytokines were quantified using the enzyme-linked immunosorbent assay for interleukin (IL)1 beta, IL2, IL6, TNF-alpha, CCL5, and macrophage inflammatory protein-1a. Protection against retinal damage was attempted with a single dose of either anti-TNF-a antibody (infliximab, 6.25 mg/kg) or control immunoglobulin G (IgG), administered intraperitoneally 15 minutes after the burn was inflicted. Corneal injury was evaluated by using TUNEL and CD45 immunolocalization and by quantifying corneal neovascularization. RESULTS: There was significant damage to the retina within 24 hours of the corneal burn being inflicted. TUNEL+ labeling was present in 80% of the retinal ganglion cells, including a few CD45+ cells. There was a 10-fold increase in the retinal inflammatory cytokines in the study groups compared with that in controls. A single intraperitoneal dose of anti-TNF-a antibody, administered 15 minutes after the burn, markedly reduced retinal TUNEL+, CD45+ labeling, and inflammatory cytokine expression, compared with that in the controls. Additionally, TNF-a blockade caused a marked reduction in corneal neovascularization, and in cornea TUNEL and CD45 labeling, 5 days after the burn. CONCLUSIONS: This study shows that alkali corneal burns can induce significant retinal damage within 24 hours. A single dose of anti-TNF-a antibody, administered 15 minutes after inflicting the burn, provides significant retinal and corneal protection. This could lead to the discovery of novel therapies for patients with alkali injuries C1 [Cade, Fabiano; Paschalis, Eleftherios I.; Regatieri, Caio V.; Vavvas, Demetrios G.; Dana, Reza; Dohlman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea Serv,Angiogenesis Lab, Boston, MA 02114 USA. RP Paschalis, EI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM eleftherios_paschalis@meei.harvard.edu FU Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear Infirmary, Boston, MA FX Supported by the Boston Keratoprosthesis Research Fund, Massachusetts Eye and Ear Infirmary, Boston, MA. NR 20 TC 13 Z9 13 U1 1 U2 8 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 APR PY 2014 VL 33 IS 4 BP 382 EP 389 DI 10.1097/ICO.0000000000000071 PG 8 WC Ophthalmology SC Ophthalmology GA AH2GZ UT WOS:000335940800020 PM 24488127 ER PT J AU Wiznia, LE Shanley, KM Federman, DG AF Wiznia, Lauren E. Shanley, Kerry M. Federman, Daniel G. TI Advanced, Neglected Basal Cell Carcinoma SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE basal cell carcinoma; neglected skin cancer; nonmelanoma skin cancer ID NONMELANOMA SKIN-CANCER; MOHS MICROGRAPHIC SURGERY; AGED 90 YEARS; LIFE EXPECTANCY; OLDER; RISK; DIAGNOSIS; MELANOMA AB Although basal cell carcinoma (BCC) rarely metastasizes and has a cure rate >95% when diagnosed early in its course, BCC causes significant morbidity and presents an enormous burden to the healthcare system worldwide. Patients who present late in the course of their disease are particularly challenging in that their treatment can be more complicated and less likely to be effective than had they presented earlier. Given the high prevalence of this malignancy and the morbidity associated with a late presentation, healthcare professionals should be familiar with the consequences of neglected BCCs, as well as their management after presentation. Knowledge of patient risk characteristics may allow earlier engagement and diagnosis of patients, before more significant morbidity occurs. C1 [Wiznia, Lauren E.] Yale Univ, Sch Med, New Haven, CT 06510 USA. VA Connecticut Healthcare Syst, New Haven, CT USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Wiznia, LE (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06510 USA. EM lauren.wiznia@yale.edu NR 32 TC 4 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD APR PY 2014 VL 107 IS 4 BP 242 EP 245 DI 10.1097/SMJ.0000000000000083 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AK9RT UT WOS:000338765100009 PM 24937518 ER PT J AU Townsend, KL Tseng, YH AF Townsend, Kristy L. Tseng, Yu-Hua TI Brown fat fuel utilization and thermogenesis SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review DE brown adipose tissue; energy expenditure; uncoupling protein 1 ID DIET-INDUCED THERMOGENESIS; DROPLET-ASSOCIATED PROTEINS; ADIPOSE-TISSUE LIPOGENESIS; PPAR-GAMMA ACTIVATION; DE-NOVO LIPOGENESIS; ACUTE COLD-EXPOSURE; LIPOPROTEIN-LIPASE; ADAPTIVE THERMOGENESIS; INDUCED OBESITY; INSULIN-RESISTANCE AB Brown adipose tissue (BAT) dissipates energy As heat to maintain optimal thermogenesis and to contribute to energy expenditure in rodents and possibly humans. The energetic processes executed by BAT require a readily-available fuel supply, which includes glucose and fatty acids (FAs). FAs become available by cellular uptake, de novo lipogenesis, and multilocular lipid droplets in brown adipocytes. BAT also possesses a great capacity for glucose uptake and metabolism, and an ability to regulate insulin sensitivity. These properties make BAT an appealing target for the treatment of obesity, diabetes, and other metabolic disorders. Recent research has provided a better understanding of the processes of fuel utilization carried out by brown adipocytes, which is the focus of the current review. C1 [Townsend, Kristy L.; Tseng, Yu-Hua] Joslin Diabet Ctr, Boston, MA 02215 USA. [Townsend, Kristy L.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Tseng, Yu-Hua] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Tseng, YH (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM yu-hua.tseng@joslin.harvard.edu FU National Institutes of Health (NIH) [R01 DK077097, P30 DK036836]; American Diabetes Association; Harvard Stem Cell Institute; NIH [T32 DK007260-33, F32 DK091996] FX The authors wish to thank E. Caniano for administrative assistance, the reviewers for thoughtful and thorough comments, and Y.M. Kwon for editing of the manuscript. Elements of some figures were produced using Servier Medical Art (http://www.servier.com). This work was supported in part by National Institutes of Health (NIH) grants R01 DK077097 (to Y-H.T.) and P30 DK036836 (Diabetes Research Center of the Joslin Diabetes Center), a research grant from the American Diabetes Association and funding from the Harvard Stem Cell Institute (to Y-H.T.). K.L.T. was funded by NIH T32 DK007260-33 and NIH F32 DK091996. NR 111 TC 38 Z9 39 U1 2 U2 23 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 2014 VL 25 IS 4 BP 168 EP 177 DI 10.1016/j.tem.2013.12.004 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AK9OI UT WOS:000338756000002 PM 24389130 ER PT J AU Crnej, A Paschalis, EI Salvador-Culla, B Tauber, A Drnovsek-Olup, B Shen, LQ Dohlman, CH AF Crnej, Alja Paschalis, Eleftherios I. Salvador-Culla, Borja Tauber, Allyson Drnovsek-Olup, Brigita Shen, Lucy Q. Dohlman, Claes H. TI Glaucoma Progression and Role of Glaucoma Surgery in Patients With Boston Keratoprosthesis SO CORNEA LA English DT Article DE Boston keratoprosthesis; glaucoma; glaucoma surgery ID TYPE-1 KERATOPROSTHESIS; I KERATOPROSTHESIS; RISK-FACTORS; COMPLICATIONS; EXPERIENCE; MANAGEMENT AB Purpose: The aim of this study was to evaluate glaucoma onset and progression after implantation of Boston Keratoprostheses (B-KPro)and the role of glaucoma surgery. Methods: Records of patients with B-KPro implantation during 2004 to 2009 were reviewed. Parameters relevant to B-KPro surgery and glaucoma status were recorded. The data were analyzed in 5 groups based on the preoperative diagnosis. Results: One hundred six eyes of 87 patients were included, and the average age was 54 +/- 6.7 years. Forty-six percent were female. Eighteen eyes had a B-KPro with a titanium back plate, and the others had a poly(methyl methacrylate) back plate. Thirty-three eyes were pseudophakic, and the rest were left aphakic. The follow-up time was 3.3 +/- 1.0 years. Indications for implantation included past infection, congenital glaucoma, trauma, autoimmune diseases, aniridia, burns, and others. Sixty-six percent of the eyes had glaucoma preoperatively, and 26% developed de novo glaucoma afterward. The mean intraocular pressure (by finger palpation) was 16.5 +/- 5.7 mm Hg. Reliable visual field tests were only available in 59% of the eyes; hence, the cup-to-disc ratio of the optic nerve head was used as the main outcome measure. In B-KPro-implanted eyes with glaucoma, 65% had undergone glaucoma surgery at some point, and 30% did not show progression. Thirty-one percent of the total cohort had disc pallor with a cup-to-disc ratio of < 0.8. Conclusions: Glaucoma in B-KPro remains a challenge, despite aggressive attempts to slow down its progression. Patients with glaucoma before B-KPro implantation should be considered for glaucoma surgery before or simultaneously with B-KPro implantation. The high number of eyes with disc pallor suggests that additional mechanisms other than elevated intraocular pressure may play a role in optic neuropathy. C1 [Crnej, Alja; Paschalis, Eleftherios I.; Salvador-Culla, Borja; Tauber, Allyson; Shen, Lucy Q.; Dohlman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv, Boston, MA USA. [Crnej, Alja; Drnovsek-Olup, Brigita] Univ Med Ctr, Eye Clin, Ljubljana, Slovenia. RP Dohlman, CH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02115 USA. EM claes_dohlman@meei.harvard.edu NR 22 TC 18 Z9 18 U1 1 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 APR PY 2014 VL 33 IS 4 BP 349 EP 354 DI 10.1097/ICO.0000000000000067 PG 6 WC Ophthalmology SC Ophthalmology GA AH2GZ UT WOS:000335940800002 PM 24531120 ER PT J AU Eastman, KL McFarland, LV Raugi, GJ AF Eastman, Kristin L. McFarland, Lynne V. Raugi, Gregory J. TI A Review of Topical Corrosive Black Salve SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Review ID BASAL-CELL CARCINOMA; NONMELANOMA SKIN-CANCER; ESCHAROTIC AGENTS; SELF-TREATMENT; SANGUINARINE; RECURRENCE; CHELERYTHRINE; APOPTOSIS; INTERNET; SURGERY AB Black salve is a compound derived from various inert ingredients, but it can be transformed into a corrosive ointment by the addition of bloodroot (Sanguinaria canadensis) or zinc chloride. Black salve products have been advertised as a natural remedy for many ailments, ranging from bee stings to skin cancer. This article reviews the current literature surrounding this compound, which in its corrosive form can be dangerous for use without medical supervision. Patients should be educated about the lack of objective evidence supporting the clinical efficacy of black salve as a skin cancer treatment, as well as the possible cosmetic defects resulting from tissue necrosis secondary to the effects of bloodroot and zinc chloride. C1 [Eastman, Kristin L.] Univ Washington, Sch Med, Seattle, WA USA. [Eastman, Kristin L.; McFarland, Lynne V.; Raugi, Gregory J.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Raugi, Gregory J.] Vet Affairs Puget Sound Hlth Care Syst, Dermatol Sect, Hosp & Specialty Med Serv, Seattle, WA 98101 USA. RP McFarland, LV (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Metropolitan Pk West,1100 Olive Way 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov FU US Department of Veterans Affairs; Department of Health Services Research & Development of the Veterans Affairs Puget Sound Health Care System FX Supported by the US Department of Veterans Affairs and the Department of Health Services Research & Development of the Veterans Affairs Puget Sound Health Care System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 33 TC 7 Z9 7 U1 1 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD APR PY 2014 VL 20 IS 4 BP 284 EP 289 DI 10.1089/acm.2012.0377 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA AK3TI UT WOS:000338347200010 PM 24175872 ER PT J AU Abdala, C Guerit, F Luo, P Shera, CA AF Abdala, Carolina Guerit, Francois Luo, Ping Shera, Christopher A. TI Distortion-product otoacoustic emission reflection-component delays and cochlear tuning: Estimates from across the human lifespan SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID COHERENT REFLECTION; HEARING-LOSS; FREQUENCY; SUPPRESSION; CHINCHILLA; BREAKING; ORIGIN; MODEL; EARS AB A consistent relationship between reflection-emission delay and cochlear tuning has been demonstrated in a variety of mammalian species, as predicted by filter theory and models of otoacoustic emission (OAE) generation. As a step toward the goal of studying cochlear tuning throughout the human lifespan, this paper exploits the relationship and explores two strategies for estimating delay trends-energy weighting and peak picking-both of which emphasize data at the peaks of the magnitude fine structure. Distortion product otoacoustic emissions (DPOAEs) at 2f(1)-f(2) were recorded, and their reflection components were extracted in 184 subjects ranging in age from prematurely born neonates to elderly adults. DPOAEs were measured from 0.5-4 kHz in all age groups and extended to 8 kHz in young adults. Delay trends were effectively estimated using either energy weighting or peak picking, with the former method yielding slightly shorter delays and the latter somewhat smaller confidence intervals. Delay and tuning estimates from young adults roughly match those obtained from SFOAEs. Although the match is imperfect, reflection-component delays showed the expected bend (apical-basal transition) near 1 kHz, consistent with a break in cochlear scaling. Consistent with other measures of tuning, the term newborn group showed the longest delays and sharpest tuning over much of the frequency range. (C) 2014 Acoustical Society of America. C1 [Abdala, Carolina; Luo, Ping] House Res Inst, Div Commun & Auditory Neurosci, Los Angeles, CA 90057 USA. [Guerit, Francois] Tech Univ Denmark, Dept Elect Engn, DK-2800 Lyngby, Denmark. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Abdala, C (reprint author), House Res Inst, Div Commun & Auditory Neurosci, 2100 West 3rd St, Los Angeles, CA 90057 USA. EM carolina.abdala@med.usc.edu FU National Institutes of Health [R01 DC003552, R01 DC003687] FX This work was supported by grants R01 DC003552 and R01 DC003687 from the National Institutes of Health. We gratefully acknowledge contributions from Sumit Dhar's laboratory at Northwestern University, and thank Srikanta Mishra, Sumaya Sidique, Abby Rogers, and Angela Garinis for data collection. We also thank Mahnaz Ahmadi for help preparing this manuscript. NR 30 TC 5 Z9 5 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2014 VL 135 IS 4 BP 1950 EP 1958 DI 10.1121/1.4868357 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AK3EX UT WOS:000338307200035 PM 25234993 ER PT J AU Fuchs, BC Hoshida, Y Fujii, T Wei, L Yamada, S Lauwers, GY McGinn, CM DePeralta, DK Chen, XT Kuroda, T Lanuti, M Schmitt, AD Gupta, S Crenshaw, A Onofrio, R Taylor, B Winckler, W Bardeesy, N Caravan, P Golub, TR Tanabe, KK AF Fuchs, Bryan C. Hoshida, Yujin Fujii, Tsutomu Wei, Lan Yamada, Suguru Lauwers, Gregory Y. McGinn, Christopher M. DePeralta, Danielle K. Chen, Xintong Kuroda, Toshihiko Lanuti, Michael Schmitt, Anthony D. Gupta, Supriya Crenshaw, Andrew Onofrio, Robert Taylor, Bradley Winckler, Wendy Bardeesy, Nabeel Caravan, Peter Golub, Todd R. Tanabe, Kenneth K. TI Epidermal Growth Factor Receptor Inhibition Attenuates Liver Fibrosis and Development of Hepatocellular Carcinoma SO HEPATOLOGY LA English DT Article ID HEPATIC STELLATE CELLS; FUNCTIONAL POLYMORPHISM; GENE-EXPRESSION; CIRRHOSIS; HEPATOCARCINOGENESIS; DISEASE; MICE; MECHANISMS; ERLOTINIB; TARGETS AB Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer-related mortality in the United States. Because of the lack of viable treatment options for HCC, prevention in high-risk patients has been proposed as an alternative strategy. The main risk factor for HCC is cirrhosis and several lines of evidence implicate epidermal growth factor (EGF) in the progression of cirrhosis and development of HCC. We therefore examined the effects of the EGF receptor (EGFR) inhibitor erlotinib on liver fibrogenesis and hepatocellular transformation in three different animal models of progressive cirrhosis: a rat model induced by repeated, low-dose injections of diethylnitrosamine (DEN), a mouse model induced by carbon tetrachloride (CCl4), and a rat model induced by bile duct ligation (BDL). Erlotinib reduced EGFR phosphorylation in hepatic stellate cells (HSC) and reduced the total number of activated HSC. Erlotinib also decreased hepatocyte proliferation and liver injury. Consistent with all these findings, pharmacological inhibition of EGFR signaling effectively prevented the progression of cirrhosis and regressed fibrosis in some animals. Moreover, by alleviating the underlying liver disease, erlotinib blocked the development of HCC and its therapeutic efficacy could be monitored with a previously reported gene expression signature predictive of HCC risk in human cirrhosis patients. Conclusion: These data suggest that EGFR inhibition using Food and Drug Administration-approved inhibitors provides a promising therapeutic approach for reduction of fibrogenesis and prevention of HCC in high-risk cirrhosis patients who can be identified and monitored by gene expression signatures. (Hepatology 2014;59:1577-1590) C1 [Fuchs, Bryan C.; Fujii, Tsutomu; Wei, Lan; Yamada, Suguru; DePeralta, Danielle K.; Kuroda, Toshihiko; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA. [Fuchs, Bryan C.; Fujii, Tsutomu; Wei, Lan; Yamada, Suguru; Lauwers, Gregory Y.; McGinn, Christopher M.; DePeralta, Danielle K.; Kuroda, Toshihiko; Lanuti, Michael; Schmitt, Anthony D.; Bardeesy, Nabeel; Golub, Todd R.; Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA. [Hoshida, Yujin; Chen, Xintong] Icahn Sch Med Mt Sinai, Liver Canc Program, Tisch Canc Inst, Div Liver Dis,Dept Med, New York, NY USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Boston, MA 02114 USA. [McGinn, Christopher M.; Lanuti, Michael; Schmitt, Anthony D.] Massachusetts Gen Hosp, Div Thorac Surg, Ctr Canc, Boston, MA 02114 USA. [Gupta, Supriya; Crenshaw, Andrew; Onofrio, Robert; Taylor, Bradley; Winckler, Wendy] Broad Inst, Cambridge, MA USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. [Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA USA. [Golub, Todd R.] Broad Inst, Canc Program, Cambridge, MA USA. [Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tanabe, Kenneth K.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA. EM ktanabe@partners.org RI Fujii, Tsutomu/M-4838-2014 FU National Institutes of Health [K01 CA140861, R01 DK099558, R01 CA076183]; Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery; Howard Hughes Medical Institute; Tucker Gosnell Center for Gastrointestinal Cancers; Aid for Cancer Research FX Supported by the National Institutes of Health (grant numbers K01 CA140861 to B.C.F., R01 DK099558 to Y.H., and R01 CA076183 to K.K.T.); the Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery to B.C.F.; Aid for Cancer Research to B.C.F.; the Howard Hughes Medical Institute to T.R.G.; and the Tucker Gosnell Center for Gastrointestinal Cancers to K.K.T. NR 37 TC 63 Z9 68 U1 6 U2 41 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 APR PY 2014 VL 59 IS 4 BP 1577 EP 1590 DI 10.1002/hep.26898 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD4VQ UT WOS:000333249800040 PM 24677197 ER PT J AU Taudorf, EH Haak, CS Erlendsson, AM Philipsen, PA Anderson, RR Paasch, U Haedersdal, M AF Taudorf, Elisabeth H. Haak, Christina S. Erlendsson, Andres M. Philipsen, Peter A. Anderson, R. Rox Paasch, Uwe Haedersdal, Merete TI Fractional Ablative Erbium YAG Laser: Histological Characterization of Relationships Between Laser Settings and Micropore Dimensions SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE erbium laser; histology; laser assisted drug delivery; MAZ; microscopic ablation zone; photothermolysis; resurfacing ID INTRAOPERATIVE MITOMYCIN-C; ASSISTED DACRYOCYSTORHINOSTOMY; ENDONASAL; REVISION; SATISFACTION; SURGERY AB Background and Objectives: Treatment of a variety of skin disorders with ablative fractional lasers (AFXL) is driving the development of portable AFXLs. This study measures micropore dimensions produced by a small 2,940 nm AFXL using a variety of stacked pulses, and determines a model correlating laser parameters with tissue effects. Materials and Methods: Ex vivo pig skin was exposed to a miniaturized 2,940 nm AFXL, spot size 225 mu m, density 5%, power levels 1.15-2.22 W, pulse durations 50-225 microseconds, pulse repetition rates 100-500 Hz, and 2, 20, or 50 stacked pulses, resulting in pulse energies of 2.3-12.8 mJ/microbeam and total energy levels of 4.6-640 mJ/microchannel. Histological endpoints were ablation depth (AD), coagulation zone (CZ) and ablation width (AW). Data were logarithmically transformed if required prior to linear regression analyses. Results for histological endpoints were combined in a mathematical model. Results: In 138 sections from 91 biopsies, AD ranged from 16 to a maximum of 1,348 mu m and increased linearly with the logarithm of total energy delivered by stacked pulses, but also depended on variations in power, pulse duration, pulse repetition rate, and pulse energy (r(2) = 0.54-0.85, P < 0.0001). Microchannels deeper than 500 mu m were created only by the highest pulse energy of 12.8 mJ/microbeam. Pulse stacking increased AD, and enlarged CZ and AW. CZ varied from 0 to 205 mu m and increased linearly with total energy (r(2) = 0.56-0.75, P < 0.0001). AW ranged from 106 to 422 mu m and increased linearly with the logarithm of number of stacked pulses (r(2) = 0.53-0.61, P < 0.001). The mathematical model estimated micropores of specific ADs with an associated range of CZs and AWs, for example, 300 mu m ADs were associated with CZs from 27 to 73 mu m and AWs from 190 to 347 mu m. Conclusions: Pulse stacking with a small, low power 2,940 nm AFXL created reproducible shallow to deep micropores, and influenced micropore configuration. Mathematical modeling established relations between laser settings and micropore dimensions, which assists in choosing laser settings for desired tissue effects. Lasers Surg. Med. 46:281-289, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Taudorf, Elisabeth H.; Haak, Christina S.; Erlendsson, Andres M.; Philipsen, Peter A.; Haedersdal, Merete] Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen NV, Denmark. [Haak, Christina S.; Anderson, R. Rox; Haedersdal, Merete] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Paasch, Uwe] Univ Leipzig, Dept Dermatol, D-04109 Leipzig, Germany. [Paasch, Uwe] Univ Leipzig, Dept Venereol, D-04109 Leipzig, Germany. [Paasch, Uwe] Univ Leipzig, Dept Allergol, D-04109 Leipzig, Germany. RP Taudorf, EH (reprint author), Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, D-92,Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. EM ehtaudorf@dadlnet.dk FU Pantec Biosolutions FX Conflicts of interest: Merete Haedersdal received research grant from Pantec Biosolutions. NR 37 TC 11 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD APR PY 2014 VL 46 IS 4 BP 281 EP 289 DI 10.1002/lsm.22228 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA AF4KE UT WOS:000334679900005 PM 24500855 ER PT J AU Greninger, DA Lowry, EA Porco, TC Naseri, A Stamper, RL Han, Y AF Greninger, Daniel A. Lowry, Eugene A. Porco, Travis C. Naseri, Ayman Stamper, Robert L. Han, Ying TI Resident-Performed Selective Laser Trabeculoplasty in Patients With Open-Angle Glaucoma SO JAMA OPHTHALMOLOGY LA English DT Article ID OCULAR HYPERTENSION; FOLLOW-UP; TRABECULECTOMY; FLUCTUATION; SURGERY AB IMPORTANCE To our knowledge, this is the first study to investigate effectiveness and complication rates of resident-performed selective laser trabeculoplasty (SLT). OBJECTIVES To evaluate the effectiveness and complications of SLT performed by resident ophthalmologists and to identify predictors for success. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series of 81 patients with open-angle glaucoma undergoing 110 SLT procedures from November 17, 2009, through December 16, 2011, at the San Francisco Veterans Affairs Medical Center. INTERVENTION Resident-performed SLT. MAIN OUTCOMES AND MEASURES Intraocular pressure (IOP) reduction. Secondary outcomes included change in eyedrop medications, complication rates, and predictors of SLT success defined as a 20% reduction in IOP. RESULTS The mean IOP at baseline, defined as the average IOP of the 2 appointments prior to the SLT procedure, was 18.7 mm Hg. The mean decrease in postoperative IOP compared with baseline was 2.2 mm Hg (12%; 95% CI, 5%-19%) at 12 months and 3.3 mm Hg (18%; 95% CI, 13%-23%), 2.8 mm Hg (15%; 95% CI, 10%-21%), and 3.6 mm Hg (19%; 95% CI, 11%-27%) at 3, 6, and 24 months, respectively (all P <.001, linear mixed-effects regression). Success rates were 36% (95% CI, 27%-47%) at 12 months and 41% (95% CI, 31%-53%), 50% (95% CI, 40%-60%), and 39% (95% CI, 26%-53%) at 3, 6, and 24 months, respectively. The most common complication was a temporary IOP spike, with increases of at least 6 mm Hg occurring in 7% (95% CI, 4%-14%) of the population. The largest IOP spike was 11 mm Hg. Increased number of laser shots performed was not associated with better IOP control but was associated with a reduction in number of eyedrop medications (P =.02). Increased baseline IOP was associated with an odds ratio for success of 1.24 (95% CI, 1.08-1.44) at 3 months, 1.20 (95% CI, 1.05-1.37) at 6 months, and 1.31 (95% CI, 1.13-1.53) at 12 months of follow-up (P =.003, P =.006, and P <.001, respectively, logistic regression). In a multivariate analysis, baseline IOP remained the greatest predictor of effectiveness. CONCLUSIONS AND RELEVANCE Resident-performed SLT obtains outcomes similar to the IOP reduction reported in the literature for attending-performed SLT with low levels of complications. Increasing the number of shots in a treatment session may lead to less long-term need for eyedrop medications. In this patient group, higher baseline IOP was the strongest predictor of treatment effectiveness. C1 [Greninger, Daniel A.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Greninger, Daniel A.; Lowry, Eugene A.; Porco, Travis C.; Naseri, Ayman; Stamper, Robert L.; Han, Ying] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Porco, Travis C.] Univ Calif San Francisco, Div Prevent Med & Publ Hlth, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Porco, Travis C.; Naseri, Ayman; Han, Ying] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Naseri, Ayman; Stamper, Robert L.; Han, Ying] San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA USA. RP Han, Y (reprint author), Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way, San Francisco, CA 94143 USA. EM ying.han@ucsf.edu NR 24 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD APR PY 2014 VL 132 IS 4 BP 403 EP 408 DI 10.1001/jamaophthalmol.2013.7651 PG 6 WC Ophthalmology SC Ophthalmology GA AJ7QF UT WOS:000337890500006 PM 24435815 ER PT J AU Rice, WL Kumar, ATN AF Rice, William L. Kumar, Anand T. N. TI Preclinical whole body time domain fluorescence lifetime multiplexing of fluorescent proteins SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescent proteins; lifetime multiplexing; autofluorescence; metastasis ID IN-VIVO; QUANTUM DOTS; ANGIOGENESIS; TOMOGRAPHY; CANCER; TUMORS; MOUSE; CELLS AB The application of time domain (TD) fluorescence lifetime multiplexing for the detection of fluorescent proteins (FPs) in whole animals, in the presence of a strong background tissue autofluorescence and excitation light leakage is discussed. Tissue autofluorescence (AF) exhibits a nonexponential temporal response, distinct from the mono-exponential decay of FPs. This allows a direct separation of FP fluorescence from AF using a dual basis function approach. We establish the detection limits of this approach using in vitro and in vivo measurements. We also demonstrate, using an experimental model of lymph node metastasis, that FP-AF lifetime multiplexing provides a greater than 30-fold improvement in contrast-to-background ratio compared with continuous wave data. In addition, we show that TD detection can simultaneously discriminate between up to three red shifted FPs placed under the skin of a nude mouse based on their distinct fluorescence lifetimes. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Rice, William L.; Kumar, Anand T. N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13 St, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu FU National Institutes of Health [NIH R01 EB015325] FX This work was supported by the National Institutes of Health grant: NIH R01 EB015325. NR 26 TC 4 Z9 4 U1 1 U2 12 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 APR PY 2014 VL 19 IS 4 AR 046005 DI 10.1117/1.JBO.19.4.046005 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AK3OO UT WOS:000338334300011 PM 24715027 ER PT J AU Zhang, Q Ivkovic, V Hu, G Strangman, GE AF Zhang, Quan Ivkovic, Vladimir Hu, Gang Strangman, Gary E. TI Twenty-four-hour ambulatory recording of cerebral hemodynamics, systemic hemodynamics, electrocardiography, and actigraphy during people's daily activities SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE wearable neuromonitoring; near-infrared spectroscopy; tissue oxygenation; brain function; circadian; sleep ID NEAR-INFRARED SPECTROSCOPY; PRACTICE PARAMETERS; NONINVASIVE DETERMINATION; OPTICAL PATHLENGTH; CIRCADIAN-RHYTHMS; BRAIN ACTIVATION; SLEEP DISORDERS; BLOOD-FLOW; FMRI; HUMANS AB The feasibility and utility of wearable 24-h multimodality neuromonitoring during daily activities are demonstrated. We have developed a fourth-generation ambulatory near infrared spectroscopy device, namely NINscan 4. NINscan 4 enables recording of brain function (via cerebral hemodynamics), systemic hemodynamics, electrocardiography, and actigraphy simultaneously and continuously for up to 24 h at 250-Hz sampling rate, during (and with minor restriction to) daily activities. We present initial 24-h human subject test results, with example analysis including (1) comparison of cerebral perfusion and oxygenation changes during wakefulness and sleep over a 24-h period and (2) capturing of hemodynamic changes prior, during and after sudden waken up in the night during sleep. These results demonstrate the first ambulatory 24-h cerebral and systemic hemodynamics monitoring, and its unique advantages including long-term data collection and analysis capability, ability to catch unpredictable transient events during activities of daily living, as well as coregistered multimodality analysis capabilities. These results also demonstrate that NINscan 4's motion artifact at 1-g head movement is smaller than physiological hemodynamic fluctuations during motionless sleep. The broader potential of this technology is also discussed. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Zhang, Quan; Ivkovic, Vladimir; Hu, Gang; Strangman, Gary E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. [Zhang, Quan; Strangman, Gary E.] Baylor Coll Med, Ctr Space Med, Houston, TX 77030 USA. RP Zhang, Q (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, 13th St,Bldg 149,Room 2651, Charlestown, MA 02129 USA. EM qzhang@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 60 TC 2 Z9 2 U1 3 U2 8 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 APR PY 2014 VL 19 IS 4 AR 047003 DI 10.1117/1.JBO.19.4.047003 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AK3OO UT WOS:000338334300031 PM 24781591 ER PT J AU Weng, D Jiang, ZK Jin, J Wu, L Lu, YF AF Weng, Ding Jiang, Ziyue Karen Jin, Jing Wu, Lily Lu, Yunfeng TI Enhanced structural stability of adenovirus nanocapsule SO PROGRESS IN NATURAL SCIENCE-MATERIALS INTERNATIONAL LA English DT Article DE Non-covalent nanocapsule; Adenovirus; Structural stability ID VIRAL VECTORS; GENE-THERAPY; IMMUNIZATION; PROGRESS; VACCINE AB Application of viral vector in gene therapy and vaccination is still limited by their structural stability, which significantly increased avoidable cost in storage and transportation. Herein a non-covalent conjugated low-pH degradable nanocapsule has been adopted to stabilize viral vectors. By utilizing a luciferase expressing adenovirus, AdCMVLuc, we succeeded in a raise of over 11 folds in AdCMVLuc's structural stability after 12 days storage at 4 degrees C. (C) 2014 Chinese Materials Research Society. Production and hosting by Elsevier B.V. All rights reserved. C1 [Weng, Ding; Jiang, Ziyue Karen; Wu, Lily; Lu, Yunfeng] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Weng, Ding] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Weng, Ding] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Jin, Jing] Getein Biotechnol Co Ltd, Nanjing 211505, Jiangsu, Peoples R China. RP Wu, L (reprint author), Univ Calif Los Angeles, 10833 Le Conte Ave,CHS 33-142, Los Angeles, CA 90095 USA. EM lwu@mednet.ucla.edu; luucla@ucla.edu FU DTRA FX We thank Jennifer Kuo for technical assistance. This work was supported by DTRA. NR 14 TC 0 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1002-0071 EI 1745-5391 J9 PROG NAT SCI-MATER JI Prog. Nat. Sci. PD APR PY 2014 VL 24 IS 2 BP 171 EP 174 DI 10.1016/j.pnsc.2014.03.001 PG 4 WC Materials Science, Multidisciplinary; Multidisciplinary Sciences SC Materials Science; Science & Technology - Other Topics GA AJ7HP UT WOS:000337868100013 ER PT J AU O'Dea, J Schainfeld, RM AF O'Dea, John Schainfeld, Robert M. TI Venous Interventions SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE veins; venae cavae; venous thromboembolism; venous thrombosis ID SUPERIOR VENA-CAVA; CATHETER-DIRECTED THROMBOLYSIS; PAGET-SCHROETTER-SYNDROME; DEEP-VEIN THROMBOSIS; ENDOVASCULAR TREATMENT; MANAGEMENT; THERAPY; DISEASE; OBSTRUCTION; PLACEMENT C1 [O'Dea, John] Boston Med Ctr, Boston, MA USA. [Schainfeld, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Schainfeld, RM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Mail Box 800, Boston, MA 02114 USA. EM rschainfeld@partners.org NR 36 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD APR PY 2014 VL 7 IS 2 BP 256 EP 265 DI 10.1161/CIRCINTERVENTIONS.113.000566 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AJ5RY UT WOS:000337746200017 PM 24737335 ER PT J AU Chadwick, KD Fletcher, AM Parrula, MC Bonner-Weir, S Mangipudy, RS Janovitz, E Graziano, MJ Roy, D Reilly, TP AF Chadwick, Kristina D. Fletcher, Anthony M. Parrula, M. Cecilia Bonner-Weir, Susan Mangipudy, Raja S. Janovitz, Evan Graziano, Michael J. Roy, Denis Reilly, Timothy P. TI Occurrence of Spontaneous Pancreatic Lesions in Normal and Diabetic Rats: A Potential Confounding Factor in the Nonclinical Assessment of GLP-1-Based Therapies SO DIABETES LA English DT Article ID DRUG-INDUCED PANCREATITIS; EXOCRINE PANCREAS; RECEPTOR ACTIVATION; NO EVIDENCE; EXENATIDE; SITAGLIPTIN; RISK; ENDOCRINE; CANCER; MODEL AB Glucagon-like peptide 1-based therapies, collectively described as incretins, produce glycemic benefits in the treatment of type 2 diabetes. Recent publications raised concern for a potential increased risk of pancreatitis and pancreatic cancer with incretins based in part on findings from a small number of rodents. However, extensive toxicology assessments in a substantial number of animals dosed up to 2 years at high multiples of human exposure do not support these concerns. We hypothesized that the lesions being attributed to incretins are commonly observed background findings and endeavored to characterize the incidence of spontaneous pancreatic lesions in three rat strains (Sprague-Dawley [S-D] rats, Zucker diabetic fatty [ZDF] rats, and rats expressing human islet amyloid polypeptide [HIP]; n = 36/group) on a normal or high-fat diet over 4 months. Pancreatic findings in all groups included focal exocrine degeneration, atrophy, inflammation, ductular cell proliferation, and/or observations in large pancreatic ducts similar to those described in the literature, with an incidence of exocrine atrophy/inflammation seen in S-D (42-72%), HIP (39%), and ZDF (6%) rats. These data indicate that the pancreatic findings attributed to incretins are common background findings, observed without drug treatment and independent of diet or glycemic status, suggesting a need to exercise caution when interpreting the relevance of some recent reports regarding human safety. C1 [Chadwick, Kristina D.; Fletcher, Anthony M.; Parrula, M. Cecilia; Mangipudy, Raja S.] Bristol Myers Squibb Co, Drug Safety Evaluat, New Brunswick, NJ 08903 USA. [Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Janovitz, Evan] Bristol Myers Squibb Co, Discovery Toxicol, Hopewell, NJ USA. [Graziano, Michael J.; Reilly, Timothy P.] Bristol Myers Squibb Co, Drug Safety Evaluat, Lawrenceville, NJ USA. [Roy, Denis] Amylin LLC, Nonclin Drug Safety, San Diego, CA USA. RP Chadwick, KD (reprint author), Bristol Myers Squibb Co, Drug Safety Evaluat, New Brunswick, NJ 08903 USA. EM kristina.chadwick@bms.com FU Bristol-Myers Squibb; Joslin Diabetes Center FX This work was supported by Bristol-Myers Squibb. At the time the work for the manuscript was planned and executed, all authors were employed by Amylin Pharmaceuticals, LLC (a wholly owned subsidiary of Bristol-Myers Squibb), Bristol-Myers Squibb, or the Joslin Diabetes Center. Some authors held stock in Bristol-Myers Squibb. S.B.-W. did not receive financial or other compensation for her histological review and input on the manuscript. No other potential conflicts of interest relevant to this article were reported. NR 40 TC 11 Z9 12 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2014 VL 63 IS 4 BP 1303 EP 1314 DI 10.2337/db13-1268 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ4FO UT WOS:000337628000025 PM 24222349 ER PT J AU Houde, AA St-Pierre, J Hivert, MF Baillargeon, JP Perron, P Gaudet, D Brisson, D Bouchard, L AF Houde, A. A. St-Pierre, J. Hivert, M. F. Baillargeon, J. P. Perron, P. Gaudet, D. Brisson, D. Bouchard, L. TI Placental lipoprotein lipase DNA methylation levels are associated with gestational diabetes mellitus and maternal and cord blood lipid profiles SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article DE fetal programming; HDL-c; hyperglycemia ID GROWTH-RESTRICTED PREGNANCIES; RELATIVE GENE-EXPRESSION; FETAL-GROWTH; HOUSEKEEPING GENES; ENDOTHELIAL LIPASE; NEWBORN WEIGHT; BIRTH-WEIGHT; GLUCOSE; TRIGLYCERIDE; PLASMA AB Placental lipoprotein lipase (LPL) is crucial for placental lipid transfer. Impaired LPL gene expression and activity were reported in pregnancies complicated by gestational diabetes mellitus (GDM) and intra-uterine growth restriction. We hypothesized that placental LPL DNA methylation is altered by maternal metabolic status and could contribute to fetal programming. The objective of this study was thus to assess whether placental LPL DNA methylation is associated with GDM and both maternal and newborn lipid profiles. Placenta biopsies were sampled at delivery from 126 women including 27 women with GDM diagnosed following a post 75 g-oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. Placental LPL DNA methylation and expression levels were determined using bisulfite pyrosequencing and quantitative real-time PCR, respectively. DNA methylation levels within LPL proximal promoter region (CpG1) and intron 1 CpG island (CpGs 2 and 3) were lower in placenta of women with GDM. DNA methylation levels at LPL-CpG1 and CpG3 were also negatively correlated with maternal glucose (2-h post OGTT; r = -0.22; P = 0.02) and HDL-cholesterol levels (third trimester of pregnancy; r = -0.20; p = 0.03), respectively. Moreover, we report correlation between LPL-CpG2 DNA methylation and cord blood lipid profile. DNA methylation levels within intron 1 CpG island explained up to 26% (r. -0.51; P< 0.001) of placental LPL mRNA expression variance. Overall, we showed that maternal metabolic profile is associated with placental LPL DNA methylation dysregulation. Our results suggest that site-specific LPL epipolymorphisms in the placenta are possibly functional and could potentially be involved in determining the future metabolic health of the newborn. C1 [Houde, A. A.; Bouchard, L.] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Houde, A. A.; St-Pierre, J.; Perron, P.; Gaudet, D.; Brisson, D.; Bouchard, L.] Chicoutimi Hosp, ECOGENE 21, Saguenay, PQ, Canada. [Houde, A. A.; St-Pierre, J.; Perron, P.; Gaudet, D.; Brisson, D.; Bouchard, L.] Chicoutimi Hosp, Clin Res Ctr, Saguenay, PQ, Canada. [Houde, A. A.; St-Pierre, J.; Perron, P.; Gaudet, D.; Brisson, D.; Bouchard, L.] Chicoutimi Hosp, Lipid Clin, Saguenay, PQ, Canada. [St-Pierre, J.] CSSS Chicoutimi, Dept Pediat, Saguenay, PQ, Canada. [Hivert, M. F.; Baillargeon, J. P.] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, M. F.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Gaudet, D.; Brisson, D.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP Bouchard, L (reprint author), CHAU Reg Chicoutimi, Lab ECOGENE 21, Pavillon Augustines AUG-5-06, Saguenay, PQ G1K 7P4, Canada. EM luigi.bouchard@usherbrooke.ca FU Fonds de la recherche en sante du Quebec (FRSQ); Canadian Diabetes Association clinical scientist award FX A.H.is a recipient of a scholarship from FRQ-S.L.B.and M.F.H.are junior research scholars from the Fonds de la recherche en sante du Quebec (FRSQ). M.F.H.is also supported by a Canadian Diabetes Association clinical scientist award. L.B., M.F.H., P.P.and J.P.B.are members of the FRSQ-funded Centre de recherche clinique Etienne- Le Bel (affiliated to Centre Hospitalier de l'Universite de Sherbrooke). NR 51 TC 9 Z9 11 U1 2 U2 10 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 EI 2040-1752 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD APR PY 2014 VL 5 IS 2 BP 132 EP 141 DI 10.1017/S2040174414000038 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AJ5VK UT WOS:000337757700008 PM 24847699 ER PT J AU Kivisakk, P Healy, BC Francois, K Gandhi, R Gholipour, T Egorova, S Sevdalinova, V Quintana, F Chitnis, T Weiner, HL Khoury, SJ AF Kivisaekk, Pia Healy, Brian C. Francois, Katiana Gandhi, Roopali Gholipour, Taha Egorova, Svetlana Sevdalinova, Velina Quintana, Francisco Chitnis, Tanuja Weiner, Howard L. Khoury, Samia J. TI Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Biomarker; disease; ELISA; multiple sclerosis; osteopontin; plasma ID CEREBROSPINAL-FLUID; DISEASE-ACTIVITY; EXPRESSION; CELLS; OSTEOPROTEGERIN; RESPONSES; SEVERITY AB Background: Osteopontin (OPN) is a pleiotropic protein with important roles in inflammation and immunity that has been suggested as a candidate biomarker for disease activity in multiple sclerosis (MS). Objective: We evaluated plasma levels of OPN in an unselected cohort of MS patients, to determine its potential as a biomarker for disease subtype and/or disease activity in a regular clinical setting. Methods: We analyzed OPN plasma levels in 492 consecutive MS patients, using a commercial enzyme-linked immunosorbent assay (ELISA). Results: OPN levels were higher in relapsing-remitting and secondary progressive MS, compared to healthy controls. Treatment with natalizumab or glatiramer acetate was associated with lower OPN levels. There was no significant association between the OPN levels and disease activity, as measured by clinical or radiological criteria. One-third of patients with high OPN levels had concurrent disorders that may also be associated with increased OPN expression, and which may mask a modest effect of MS disease activity on OPN levels. Conclusion: Our data do not support a role for circulating OPN levels as a biomarker for disease activity in a heterogeneous clinical setting, but does not rule out a potential role in the cerebrospinal fluid, in a controlled setting such as a clinical trial, or in concert with other biomarkers. C1 [Kivisaekk, Pia; Healy, Brian C.; Francois, Katiana; Gandhi, Roopali; Gholipour, Taha; Egorova, Svetlana; Sevdalinova, Velina; Quintana, Francisco; Chitnis, Tanuja; Weiner, Howard L.; Khoury, Samia J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Khoury, Samia J.] Amer Univ Beirut, Abu Haidar Neurosci Inst, Beirut, Lebanon. RP Khoury, SJ (reprint author), Brigham & Womens Hosp, Harvard Inst Med, Ctr Neurol Dis, Room NRB641,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM skhoury@partners.org OI Egorova, Svetlana/0000-0002-9873-092X FU EMD Serono FX This work was funded in part by an investigator-initiated research grant from EMD Serono. NR 33 TC 13 Z9 14 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD APR PY 2014 VL 20 IS 4 BP 438 EP 444 DI 10.1177/1352458513503052 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI9WO UT WOS:000337295300009 PM 24005026 ER PT J AU Kim, YW Zipfel, GJ Ogilvy, CS Pricola, KL Welch, BG Shakir, N Patel, B Reavey-Cantwell, JF Kelman, CR Albuquerque, FC Kalani, MYS Hoh, BL AF Kim, Young Woo Zipfel, Gregory J. Ogilvy, Christopher S. Pricola, Katie L. Welch, Babu G. Shakir, Nabeel Patel, Bhuvic Reavey-Cantwell, John F. Kelman, Craig R. Albuquerque, Felipe C. Kalani, M. Yashar S. Hoh, Brian L. TI Preconditioning Effect on Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage SO NEUROSURGERY LA English DT Article DE Aneurysm; Preconditioning; Subarachnoid Hemorrhage; Vasospasm ID ACUTE BRAIN-INJURY; ISCHEMIC TOLERANCE; CLINICAL-TRIAL; LIPOPOLYSACCHARIDE; RAT; MECHANISMS; PROTECTION; OCCLUSION; STROKE AB BACKGROUND: Recent experimental evidence indicates that endogenous mechanisms against cerebral vasospasm can be induced via preconditioning. OBJECTIVE: To determine whether these vascular protective mechanisms are also present in vivo in humans with aneurysmal subarachnoid hemorrhage. METHODS: A multicenter retrospective cohort of patients with aneurysmal subarachnoid hemorrhage was examined for ischemic preconditioning stimulus: preexisting steno-occlusive cerebrovascular disease (CVD) and/or previous cerebral infarct. Generalized estimating equation models were performed to determine the effect of the preconditioning stimulus on the primary end points of radiographic vasospasm, symptomatic vasospasm, and vasospasm-related delayed cerebral infarction and the secondary end point of discharge modified Rankin Scale score. RESULTS: Of 1043 patients, 321 (31%) had preexisting CVD and 437 (42%) had radiographic vasospasm. Patients with preexisting CVD were less likely to develop radiographic vasospasm (odds ratio = 0.67; 95% confidence interval = 0.489-0.930; P = .02) but had no differences in other end points. In terms of the secondary end point, patients with preexisting CVD did not differ significantly from patients without preexisting CVD in mortality or unfavorable outcome in multivariate analyses, although patients with preexisting CVD were marginally more likely to die (P = .06). CONCLUSION: This retrospective case-control study suggests that endogenous protective mechanisms against cerebral vasospasm-a preconditioning effect-may exist in humans, although these results could be the effect of atherosclerosis or some combination of preconditioning and atherosclerosis. Additional studies investigating the potential of preconditioning in aneurysmal subarachnoid hemorrhage are warranted. C1 [Kim, Young Woo] Catholic Univ Korea, Bucheon St Marys Hosp, Dept Neurosurg, Puchon, South Korea. [Zipfel, Gregory J.; Patel, Bhuvic] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA. [Ogilvy, Christopher S.; Pricola, Katie L.] Massachusetts Gen Hosp, Neurovasc Serv, Boston, MA 02114 USA. [Welch, Babu G.; Shakir, Nabeel] UT Southwestern Med Ctr, Dept Radiol, Dallas, TX USA. [Reavey-Cantwell, John F.; Kelman, Craig R.] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA USA. [Albuquerque, Felipe C.; Kalani, M. Yashar S.] St Josephs Hosp, Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ USA. [Hoh, Brian L.] Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. RP Hoh, BL (reprint author), Univ Florida, Dept Neurosurg, POB 100265, Gainesville, FL 32610 USA. EM brian.hoh@neurosurgery.ufl.edu OI Kalani, M. Yashar/0000-0002-5923-1255 FU National Institute of Health [P50 NS055977, 1R01 NS071011-01A1]; Washington University Center for Investigation of Membrane Excitability Diseases; American Heart Association; Neurosurgery Research and Education Foundation; Brain Aneurysm Foundation; Washington University Institute of Clinical and Translational Sciences; National Institutes of Health; American Medical Association FX Dr Zipfel has received research grants from the National Institute of Health (P50 NS055977, 1R01 NS071011-01A1), Washington University Center for Investigation of Membrane Excitability Diseases, American Heart Association, Neurosurgery Research and Education Foundation, Brain Aneurysm Foundation, and Washington University Institute of Clinical and Translational Sciences. Dr Welch serves as a consultant to Stryker Neurovascular. Dr Hoh has received research grants from the National Institutes of Health. Dr Kalani has received research support from the American Medical Association. All other authors have no personal financial disclosures in this article. NR 36 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 2014 VL 74 IS 4 BP 351 EP 358 DI 10.1227/NEU.0000000000000282 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AJ5KW UT WOS:000337722100019 PM 24378827 ER PT J AU Walcott, BP Hattangadi-Gluth, JA Stapleton, CJ Ogilvy, CS Chapman, PH Loeffler, JS AF Walcott, Brian P. Hattangadi-Gluth, Jona A. Stapleton, Christopher J. Ogilvy, Christopher S. Chapman, Paul H. Loeffler, Jay S. TI Proton Beam Stereotactic Radiosurgery for Pediatric Cerebral Arteriovenous Malformations SO NEUROSURGERY LA English DT Article DE Arteriovenous; AVM; Bragg peak; Pediatric; Proton; Radiosurgery; Stereotactic ID GAMMA-KNIFE SURGERY; NATURAL-HISTORY; DOSE-RESPONSE; BRAIN; EMBOLIZATION; RISK; HEMORRHAGE; THERAPY; COMPLICATIONS; OBLITERATION AB BACKGROUND: For cerebral arteriovenous malformations (AVMs) determined to be high risk for surgery or endovascular embolization, stereotactic radiosurgery (SRS) is considered the mainstay of treatment. OBJECTIVE: To determine the outcomes of pediatric patients with AVMs treated with proton SRS. METHODS: We reviewed the records of 44 consecutively treated pediatric patients (younger than 18 years of age) who underwent proton SRS at our institution from 1998 to 2010. The median target volume was 4.5 +/- 5.9 mL (range, 0.3-29.0 mL) and the median maximal diameter was 3.6 +/- 1.5 cm (range, 1-6 cm). Radiation was administered with a median prescription dose of 15.50 +/- 1.87 CGE to the 90% isodose. RESULTS: At a median follow-up of 52 +/- 25 months, 2 patients (4.5%) had no response, 24 patients (59.1%) had a partial response, and 18 patients (40.9%) experienced obliteration of their AVM. The median time to obliteration was 49 +/- 26 months, including 17 patients who underwent repeat proton radiosurgery. Four patients (9%) experienced hemorrhage after treatment at a median time of 45 +/- 15 months. Univariate analysis identified modified AVM scale score (P = .045), single fraction treatment (0.04), larger prescription dose (0.01), larger maximum dose (<0.001), and larger minimum dose (0.01) to be associated with AVM obliteration. CONCLUSION: High-risk AVMs can be safely treated with proton radiosurgery in the pediatric population. Because protons deposit energy more selectively than photons, there is the potential benefit of protons to lower the probability of damage to healthy tissue in the developing brain. C1 [Walcott, Brian P.; Stapleton, Christopher J.; Chapman, Paul H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Hattangadi-Gluth, Jona A.] Univ Calif San Diego, Dept Radiat Oncol, San Diego, CA 92103 USA. [Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NIH [5P01CA021239-26] FX Dr Loeffler is the recipient of NIH grant 5P01CA021239-26. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 46 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD APR PY 2014 VL 74 IS 4 BP 367 EP 373 DI 10.1227/NEU.0000000000000294 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AJ5KW UT WOS:000337722100023 PM 24448188 ER PT J AU Nair, D Kumaraswamy, VM Braver, D Kilbride, RD Borges, LF Simon, MV AF Nair, Dinesh Kumaraswamy, Vishakhadatta M. Braver, Diana Kilbride, Ronan D. Borges, Lawrence F. Simon, Mirela V. TI Dorsal Column Mapping via Phase Reversal Method: The Refined Technique and Clinical Applications SO NEUROSURGERY LA English DT Article DE Dorsal column mapping; Phase reversal; Somatosensory evoked potentials ID RESECTION AB BACKGROUND: Safe resection of intramedullary spinal cord tumors can be challenging, because they often alter the cord anatomy. Identification of neurophysiologically viable dorsal columns (DCs) and of neurophysiologically inert tissue, eg, median raphe (MR), as a safe incision site is crucial for avoiding postoperative neurological deficits. We present our experience with and improvements made to our previously described technique of DC mapping, successfully applied in a series of 12 cases. OBJECTIVE: To describe a new, safe, and reliable technique for intraoperative DC mapping. METHODS: The right and left DCs were stimulated by using a bipolar electric stimulator and the triggered somatosensory evoked potentials recorded from the scalp. Phase reversal and amplitude changes of somatosensory evoked potentials were used to neurophysiologically identify the laterality of DCs, the inert MR, as well as other safe incision sites. RESULTS: The MR location was neurophysiologically confirmed in all patients in whom this structure was first visually identified as well as in those in whom it was not, with 1 exception. DCs were identified in all patients, regardless of whether they could be visually identified. In 3 cases, negative mapping with the use of this method enabled the surgeon to reliably identify additional inert tissue for incision. None of the patients had postoperative worsening of the DC function. CONCLUSION: Our revised technique is safe and reliable, and it can be easily incorporated into routine intramedullary spinal cord tumor resection. It provides crucial information to the neurosurgeon to prevent postoperative neurological deficits. C1 [Nair, Dinesh; Kumaraswamy, Vishakhadatta M.; Braver, Diana; Kilbride, Ronan D.; Simon, Mirela V.] Massachusetts Gen Hosp, Dept Neurol, Neurophysiol Div, Boston, MA 02114 USA. [Nair, Dinesh; Kumaraswamy, Vishakhadatta M.; Braver, Diana; Kilbride, Ronan D.; Borges, Lawrence F.; Simon, Mirela V.] Harvard Univ, Sch Med, Boston, MA USA. [Borges, Lawrence F.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kumaraswamy, Vishakhadatta M.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. RP Simon, MV (reprint author), Massachusetts Gen Hosp, WACC 739-G,55 Fruit St, Boston, MA 02114 USA. EM mvsimon@partners.org NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD APR PY 2014 VL 74 IS 4 BP 437 EP 446 DI 10.1227/NEU.0000000000000287 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AJ5KW UT WOS:000337722100035 PM 24448182 ER PT J AU Chaparro, LE Furlan, AD Deshpande, A Mailis-Gagnon, A Atlas, S Turk, DC AF Chaparro, Luis Enrique Furlan, Andrea D. Deshpande, Amol Mailis-Gagnon, Angela Atlas, Steven Turk, Dennis C. TI Opioids Compared With Placebo or Other Treatments for Chronic Low Back Pain An Update of the Cochrane Review SO SPINE LA English DT Article DE analgesics; opioid/adverse effects; opioid/therapeutic use; buprenorphine/therapeutic use; Cochrane Review; hydromorphone/therapeutic use; low back pain/drug therapy; metaanalysis; morphine/therapeutic use; oxycodone/therapeutic use; oxymorphone/therapeutic use; sciatica/drug therapy; systematic review; tramadol/therapeutic use ID CHRONIC NONCANCER PAIN; TRAMADOL/ACETAMINOPHEN COMBINATION TABLETS; BUPRENORPHINE TRANSDERMAL SYSTEM; OXYMORPHONE EXTENDED-RELEASE; DOUBLE-BLIND; CONTROLLED-TRIAL; EFFICACY; SAFETY; MODERATE; THERAPY AB Study Design. Systematic review and meta-analysis. Objective. To assess the efficacy of opioids in adults with chronic low back pain (CLBP). Summary of Background Data. Opioids for CLBP has increased dramatically. However, the benefits and risks remain unclear. Methods. We updated a 2007 Cochrane Review through October 2012 of randomized controlled trials from multiple databases. Use of noninjectable opioids in CLBP for at least 4 weeks was compared with placebo or other treatments; comparisons with different opioids were excluded. Outcomes included pain and function using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (CIs), and absolute risk difference with 95% CI for adverse effects. Study quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation criteria. Results. Fifteen trials (5540 participants), including twelve new, met the criteria. Tramadol was better than placebo for pain (SMD, -0.55; 95% CI, -0.66 to -0.44) and function (SMD, -0.18; 95% CI, -0.29 to -0.07). Compared with placebo, transdermal buprenorphine decreased pain (SMD, -2.47; 95% CI, -2.69 to -2.25), but not function (SMD, -0.14; 95% CI, -0.53 to 0.25). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), were better than placebo for pain (SMD, -0.43; 95% CI, -0.52 to -0.33) and function (SMD, -0.26; 95% CI, -0.37 to -0.15). One trial demonstrated little difference with tramadol compared with celecoxib for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for pain or function. Reviewed trials had low to moderate quality, high drop-out rates, short duration, and limited interpretability of functional improvement. No serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism) were reported. Conclusion. There is evidence of short-term efficacy (moderate for pain and small for function) of opioids to treat CLBP compared with placebo. The effectiveness and safety of long-term opioid therapy for treatment of CLBP remains unproven. C1 [Chaparro, Luis Enrique] Hosp Pablo Tobon Uribe, Dept Anesthesiol, Medellin, Colombia. [Furlan, Andrea D.] Inst Work & Hlth, Toronto, ON, Canada. [Deshpande, Amol] Univ Hlth Network, Toronto Western Hosp, Comprehens Pain Program, Toronto, ON, Canada. Comprehens Pain Program, Toronto Western Hosp, Dept Med, Toronto, ON, Canada. [Atlas, Steven] Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Chaparro, LE (reprint author), Hosp Pablo Tobon Uribe, Dept Anesthesiol, Medellin, Colombia. EM luisdr74@yahoo.com NR 38 TC 45 Z9 49 U1 3 U2 11 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 APR 1 PY 2014 VL 39 IS 7 BP 556 EP 563 DI 10.1097/BRS.0000000000000249 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AJ1MC UT WOS:000337419100013 PM 24480962 ER PT J AU Baker, JF Conaghan, PG Smolen, JS Aletaha, D Shults, J Emery, P Baker, DG Ostergaard, M AF Baker, Joshua F. Conaghan, Philip G. Smolen, Josef S. Aletaha, Daniel Shults, Justine Emery, Paul Baker, Daniel G. Ostergaard, Mikkel TI Development and Validation of Modified Disease Activity Scores in Rheumatoid Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; METHOTREXATE THERAPY; CLINICAL-PRACTICE; ACTIVITY INDEX; DOUBLE-BLIND; GO-FORWARD; PHASE-III; GOLIMUMAB; ANTIBODY; VALIDITY AB Objective. To develop and validate composite disease activity scores, based on widely available clinical measures, that would demonstrate improved correlation with detection of synovitis on magnetic resonance imaging (MRI) and radiographic progression, in comparison with conventional measures, in patients with rheumatoid arthritis (RA). Methods. This study was conducted as a secondary study of 2 RA clinical trials, GO-BEFORE (development cohort) and GO-FORWARD (validation cohort). Generalized estimating equations were used to evaluate independent cross-sectional associations of component variables (from all time points) with concurrent MRI measures of synovitis and bone edema in the development cohort. Based on regression coefficients, modified versions of the Disease Activity Score in 28 joints (M-DAS28), Simplified Disease Activity Index (M-SDAI), and Clinical Disease Activity Index (M-CDAI) were generated for each subject in the validation cohort. The M-DAS28, M-SDAI, and M-CDAI scores were compared to conventional scores of disease activity with regard to associations with MRI measures of synovitis and radiographic progression, assessed using Pearson's and Spearman's correlations, linear/logistic regression, and receiver operating characteristic analysis. Results. Four variables were independently associated with MRI-detected synovitis and bone edema in the development cohort: C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), swollen joint count in 28 joints (SJC28), and evaluator's global assessment of disease activity using a visual analog scale (EvGA score). Modified disease activity scores were generated using the regression coefficients obtained in the synovitis models for all subjects in the validation cohort; modified scores were calculated as M-DAS28 x 0.49 x ln(CRP) + 0.15 x SJC28 + 0.22 x EvGA + 1 and M-SDAI = CRP + SJC28 + EvGA. Both modified and conventional disease activity scores correlated significantly with MRI measures of synovitis. Modified scores showed superior correlation with synovitis, as compared to conventional scores, at all time points (P < 0.05). Furthermore, the M-DAS28 and M-SDAI had superior test characteristics for prediction of radiographic progression at 52 weeks (both P < 0.05). Conclusion. Modified disease activity scores demonstrated superior correlation with MRI detection of synovitis at all time points, and more accurately predicted radiographic progression in patients with RA in a clinical trial setting. C1 [Baker, Joshua F.; Shults, Justine] Univ Penn, Philadelphia, PA 19104 USA. [Baker, Joshua F.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Conaghan, Philip G.] Univ Leeds, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Conaghan, Philip G.] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. [Smolen, Josef S.; Aletaha, Daniel] Med Univ Vienna, Vienna, Austria. [Emery, Paul] Univ Leeds, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds Inst Rheumat & Musculoskeletal Med, Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. [Emery, Paul] Chapel Allerton Hosp, Leeds, W Yorkshire, England. [Baker, Daniel G.] Janssen Res & Dev LLC, Spring House, PA USA. [Ostergaard, Mikkel] Glostrup Cty Hosp, Copenhagen, Denmark. [Ostergaard, Mikkel] Univ Copenhagen, Copenhagen, Denmark. RP Baker, JF (reprint author), Univ Penn, Dept Med, Div Rheumatol, Hosp Univ Penn, 8 Penn Tower Bldg,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu FU Janssen Biotech FX Funding for the original GO-BEFORE and GO-FORWARD randomized clinical trials was provided by Janssen Biotech. There was no additional funding for this secondary study. Dr. D. G. Baker is an employee of Janssen Biotech. NR 17 TC 16 Z9 16 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD APR PY 2014 VL 66 IS 4 BP 794 EP 802 DI 10.1002/art.38304 PG 9 WC Rheumatology SC Rheumatology GA AJ0QR UT WOS:000337361000005 PM 24757132 ER PT J AU Kwoh, CK Roemer, FW Hannon, MJ Moore, CE Jakicic, JM Guermazi, A Green, SM Evans, RW Boudreau, R AF Kwoh, C. Kent Roemer, Frank W. Hannon, Michael J. Moore, Carolyn E. Jakicic, John M. Guermazi, Ali Green, Stephanie M. Evans, Rhobert W. Boudreau, Robert TI Effect of Oral Glucosamine on Joint Structure in Individuals With Chronic Knee Pain SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID BONE-MARROW ABNORMALITIES; DOUBLE-BLIND; CHONDROITIN SULFATE; CARTILAGE LOSS; LONGITUDINAL CHANGES; LESION ASSESSMENT; CONTROLLED-TRIAL; HEALTH-STATUS; OSTEOARTHRITIS; PROGRESSION AB Objective. To determine the short-term efficacy of oral glucosamine supplementation by evaluating structural lesions in the knee joints, as assessed using 3T magnetic resonance imaging (MRI). Methods. This study was designed as a randomized, double-blind, placebo-controlled trial. Recruitment was performed via mass mailings and an arthritis registry in southwestern Pennsylvania. In total, 201 participants with mild-to-moderate pain in one or both knees, as defined by a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score >= 25 and <= 100, were enrolled. Of these subjects, 69.2% had a Kellgren/Lawrence grade >= 2 in at least 1 knee. Participants received 24 weeks of treatment with 1,500 mg glucosamine hydrochloride in beverage form or a placebo beverage. The primary outcome was decreased worsening of cartilage damage on 3T MRI of both knees, assessed according to a validated scoring system, the Whole-Organ MRI Score (WORMS). Secondary outcomes included change in bone marrow lesion (BML) scores in all knees and change in excretion of urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II). Results. The adjusted odds ratio (OR) for the likelihood of decreased cartilage damage over 24 weeks in any WORMS-scored subregion of the knee in the glucosamine treatment group compared to the control group was 0.938 (95% confidence interval [ 95% CI] 0.528, 1.666). Compared to subjects treated with glucosamine, control subjects showed more improvement in BMLs (adjusted OR 0.537, 95% CI 0.291, 0.990) but no difference in worsening BMLs (adjusted OR 0.691, 95% CI 0.410, 1.166) over 24 weeks. There was no indication that treatment with glucosamine decreased the excretion of urinary CTX-II (beta = -0.10, 95% CI -0.21, 0.002). Conclusion. The results of this short-term study provide no evidence of structural benefits (i.e., improvements in MRI morphologic features or urinary CTX-II excretion) from glucosamine supplementation in individuals with chronic knee pain. C1 [Kwoh, C. Kent; Hannon, Michael J.; Jakicic, John M.; Green, Stephanie M.; Evans, Rhobert W.; Boudreau, Robert] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kwoh, C. Kent; Guermazi, Ali] Univ Arizona, Tucson, AZ USA. [Roemer, Frank W.] Boston Univ, Boston, MA 02215 USA. [Roemer, Frank W.] Klinikum Augsburg, Augsburg, Germany. [Moore, Carolyn E.] Texas Womans Univ, Houston, TX USA. RP Kwoh, CK (reprint author), Univ Arizona, 1501 North Campbell Ave,Room 8303, Tucson, AZ 85724 USA. EM kwoh@arthritis.arizona.edu FU Beverage Institute for Health & Wellness, The Coca-Cola Company; Multidisciplinary Clinical Research Center for Musculoskeletal and Skin Diseases FX Funding for this study was provided by the Beverage Institute for Health & Wellness, The Coca-Cola Company. All statistical analyses were performed at the University of Pittsburgh and were partially supported by the Multidisciplinary Clinical Research Center for Musculoskeletal and Skin Diseases. The Coca-Cola Company had no role in the performance of the statistical analyses. Dr. Moore, formerly Principal Scientist at the Beverage Institute for Health & Wellness, The Coca-Cola Company, was involved with monitoring all aspects of study progress for the funding agency and coordinated the production of the glucosamine beverage, as well as the quality assurance checks on the stability of the beverage contents. Since 2008, Dr. Moore has been a faculty member at Texas Woman's University and was not associated with the Beverage Institute when the study radiographs and MRIs were analyzed. Dr. Moore participated in writing and gave final approval of the manuscript. NR 53 TC 9 Z9 10 U1 6 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD APR PY 2014 VL 66 IS 4 BP 930 EP 939 DI 10.1002/art.38314 PG 10 WC Rheumatology SC Rheumatology GA AJ0QR UT WOS:000337361000018 PM 24616448 ER PT J AU Inamoto, Y Pidala, J Chai, XY Kurland, BF Weisdorf, D Flowers, MED Palmer, J Arai, S Jacobsohn, D Cutler, C Jagasia, M Goldberg, JD Martin, PJ Pavletic, SZ Vogelsang, GB Lee, SJ Carpenter, P AF Inamoto, Yoshihiro Pidala, Joseph Chai, Xiaoyu Kurland, Brenda F. Weisdorf, Daniel Flowers, Mary E. D. Palmer, Jeanne Arai, Sally Jacobsohn, David Cutler, Corey Jagasia, Madan Goldberg, Jenna D. Martin, Paul J. Pavletic, Steven Z. Vogelsang, Georgia B. Lee, Stephanie J. Carpenter, Paul A. TI Assessment of Joint and Fascia Manifestations in Chronic Graft-Versus-Host Disease SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CHRONIC GVHD; CLINICAL-TRIALS; RISK-FACTORS; VALIDATION; CRITERIA; VALIDITY; OUTCOMES AB Objective. To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results. Methods. In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions. Results. Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician-and patient-perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician-and patient-perceived worsening, but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Conclusion. Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases. C1 [Inamoto, Yoshihiro; Chai, Xiaoyu; Kurland, Brenda F.; Flowers, Mary E. D.; Martin, Paul J.; Pavletic, Steven Z.; Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Kurland, Brenda F.] Univ Pittsburgh, Pittsburgh, PA USA. [Weisdorf, Daniel] Univ Minnesota, Minneapolis, MN USA. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Arai, Sally] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Goldberg, Jenna D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA. [Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Carpenter, P (reprint author), Fred Hutchinson Canc Res Ctr, D5-290,POB 19024, Seattle, WA 98109 USA. EM pcarpent@fhcrc.org OI Kurland, Brenda/0000-0002-5669-0595 FU NIH [CA-118953, CA-163438, CA-047904]; NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science; National Cancer Institute [U54-CA-163438]; Fred Hutchinson Cancer Research Center FX Supported by the NIH (grants CA-118953, CA-163438, and CA-047904). The Chronic GVHD Consortium is a part of the NIH Rare Diseases Clinical Research Network, which is supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science, the National Cancer Institute (grant U54-CA-163438), and the Fred Hutchinson Cancer Research Center. NR 26 TC 13 Z9 13 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD APR PY 2014 VL 66 IS 4 BP 1044 EP 1052 DI 10.1002/art.38293 PG 9 WC Rheumatology SC Rheumatology GA AJ0QR UT WOS:000337361000031 PM 24757155 ER PT J AU Boyer, M Tsao, MS Janne, P Ramalingam, S Pitman Lowenthal, S Alam, M AF Boyer, Michael Tsao, Ming-Sound Jaenne, Pasi Ramalingam, Suresh Pitman Lowenthal, Susan Alam, Mahmood TI Preparing for tomorrow: Molecular diagnostics and the changing nonsmall cell lung cancer landscape SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Review DE anaplastic lymphoma kinase (ALK) fusion gene; carcinoma; epidermal growth factor receptor mutation; molecular testing; nonsmall cell lung; targeted therapy ID GROWTH-FACTOR-RECEPTOR; PHASE-II TRIAL; INTERNATIONAL-ASSOCIATION; 1ST-LINE TREATMENT; KINASE INHIBITORS; EGFR MUTATIONS; OPEN-LABEL; ALK; GEFITINIB; CHEMOTHERAPY AB Over the last 10 to 15 years, the landscape of lung cancer has changed dramatically. Where cancers were previously described rather simplistically according to histological subtype, now molecular understanding of tumors has particularly resulted in segmentation of nonsmall cell lung cancer into many different subtypes. A multidisciplinary approach integrating a molecular testing algorithm that ideally includes reflex testing at diagnosis is recommended. This offers clinicians the opportunity to target treatment according to subtype. Identifying patients with rearrangements, such as those associated with the echinoderm microtubule-associated protein-like 4 (EML-4) anaplastic lymphoma kinase (ALK) fusion gene (the major focus of this paper) has allowed clinicians to tailor therapy to target these mutations. The challenge that faces clinicians treating lung cancer is how best to implement the science that sits behind these targeted therapies in clinical practice through the identification of appropriate patients. Precision medicine can lead to the choice of the right medicine for the right patients and is proving to be a better approach than treating unselected patients with systemic chemotherapy. C1 [Boyer, Michael] Pfizer, Chris OBrien Lifehouse, Sydney, NSW, Australia. [Alam, Mahmood] Pfizer, Oncol Business Unit, Sydney, NSW, Australia. [Tsao, Ming-Sound] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Jaenne, Pasi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ramalingam, Suresh] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Pitman Lowenthal, Susan] Pfizer Oncol, Clin Dev & Med Affairs, New York, NY USA. RP Alam, M (reprint author), Pfizer Oncol, 38-42 Wharf Rd, West Ryde, NSW 2114, Australia. EM Mahmood.Alam2@pfizer.com FU Pfizer; Pfizer Oncology; Pfizer Inc. FX This manuscript is based on coverage of a Pfizer sponsored education symposium at the 15th World Lung Cancer Conference, held in Sydney on October 27, 2013. This symposium was organized and funded by Pfizer Oncology and was conducted in accordance with Medicines Australia Code of Conduct. Attendance was limited to healthcare professionals registered to attend World Lung Cancer Conference. The symposium was chaired by Professor Michael Boyer, and included three independent presentations from Professors Ming-Sound Tsao, Pasi Janne and Suresh Ramalingam, followed by a panel discussion. Dr Susan Pitman Lowenthal and Dr Mahmood Alam from Pfizer designed the program, facilitated and reviewed the content of the presentations and the manuscript. Publication of this supplement has been supported through an independent educational grant from Pfizer Oncology. The authors Michael Boyer, Ming-Sound Tsao, Pasi Janne and Suresh Ramalingam have received honoraria and/or research funding from Pfizer Inc. NR 50 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD APR PY 2014 VL 10 SU 2 SI SI BP 2 EP 10 DI 10.1111/ajco.12189 PG 9 WC Oncology SC Oncology GA AJ2TR UT WOS:000337516800002 PM 24673735 ER PT J AU Kadayifci, A Brugge, WR AF Kadayifci, Abdurrahman Brugge, William R. TI Endoscopic ultrasound-guided fine-needle aspiration for the differential diagnosis of intraductal papillary mucinous neoplasms and size stratification for surveillance SO ENDOSCOPY LA English DT Letter ID INTERNATIONAL CONSENSUS GUIDELINES; PANCREATIC CYSTIC NEOPLASMS; MALIGNANCY; MANAGEMENT; CYTOLOGY; IPMN C1 [Kadayifci, Abdurrahman] Massachusetts Gen Hosp, GI Associates 3H, Boston, MA 02114 USA. RP Kadayifci, A (reprint author), Massachusetts Gen Hosp, GI Associates 3H, Zero Emerson Pl Blossom St, Boston, MA 02114 USA. EM akadayifci@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD APR PY 2014 VL 46 IS 4 BP 356 EP 356 PG 1 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AI8HT UT WOS:000337153500019 ER PT J AU Purvis, S Gion, T Kennedy, G Rees, S Safdar, N VanDenBergh, S Weber, J AF Purvis, Suzanne Gion, Therese Kennedy, Gregory Rees, Susan Safdar, Nasia VanDenBergh, Shelly Weber, Jessica TI Catheter-Associated Urinary Tract Infection A Successful Prevention Effort Employing a Multipronged Initiative at an Academic Medical Center SO JOURNAL OF NURSING CARE QUALITY LA English DT Article DE catheter-related infections; patient outcome assessment; quality improvement; urinary tract infections ID HOSPITALIZED-PATIENTS; EPIDURAL ANALGESIA; UNITED-STATES; CARE AB An interdisciplinary clinical improvement workgroup was formed at this academic medical center with the goal of reducing catheter-associated urinary tract infections (CAUTIs). In 2011, the CAUTI rate was noted to be 4.7 CAUTIs per 1000 catheter days. Rounding by 2 lead clinical nurse specialists revealed deficiencies in current practice, which were addressed with multifaceted strategies, including evidence-based indwelling urinary catheter and bladder management protocols, education of staff, reporting of data, and utilization of an icon in the electronic health record (EHR). After the implementation of these strategies, the CAUTI rate decreased and was noted to be 2.4 in February 2013. In addition to this, there was a downward trend line for catheter days. C1 [Purvis, Suzanne; Gion, Therese; VanDenBergh, Shelly; Weber, Jessica] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Rees, Susan] Univ Wisconsin Hosp & Clin, Dev Nursing & Patient Care Serv, Madison, WI 53792 USA. [Kennedy, Gregory] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Infect Dis, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Purvis, S (reprint author), Univ Wisconsin Hosp & Clin, 600 Highland Ave,MC 8340, Madison, WI 53792 USA. EM spurvis@uwhealth.org NR 16 TC 6 Z9 7 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-3631 EI 1550-5065 J9 J NURS CARE QUAL JI J. Nurs. Care Qual. PD APR-JUN PY 2014 VL 29 IS 2 BP 141 EP 148 DI 10.1097/NCQ.0000000000000037 PG 8 WC Nursing SC Nursing GA AI9VJ UT WOS:000337289200010 PM 24316667 ER PT J AU Cho, HY Nasir, HH Sobrin, L AF Cho, H. Y. Nasir, H. H. Sobrin, L. TI Focal Laser Photocoagulation and Photodynamic Therapy for Lupus Choroidopathy SO LUPUS LA English DT Article DE Photodynamic therapy; focal laser photocoagulation; lupus; choroidopathy ID CENTRAL SEROUS CHORIORETINOPATHY; FOLLOW-UP; ERYTHEMATOSUS; TRIAL AB To describe the results of photodynamic therapy (PDT) and/or focal laser photocoagulation in the treatment of serous retinal detachments secondary to lupus choroidopathy. Methods: The medical records of three patients with serous detachments secondary to lupus choroidopathy who were treated with PDT and/or focal laser photocoagulation were reviewed. Concomitant systemic medical therapy as well as visual acuity and optical coherence tomography (OCT) outcomes were recorded. Results: All patients received systemic immunosuppressive therapy and had control of their extraocular manifestations prior to PDT and/or laser photocoagulation. One patient received only focal laser photocoagulation and had complete resolution of the subretinal fluid on OCT. The two other patients received a combination of PDT and focal laser treatment. One had improvement in vision and resolution of subretinal fluid on OCT. The second patient, who had longstanding lupus choroidopathy and associated subretinal fluid and macular edema, had only a significant decrease in fluid on OCT but no vision improvement. Conclusion: In conjunction with control of systemic disease, PDT and/or focal laser photocoagulation can be successful in resolving subretinal fluid secondary to lupus choroidopathy. C1 [Cho, H. Y.; Nasir, H. H.; Sobrin, L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Uveitis & Retina Serv, Boston, MA 02114 USA. [Cho, H. Y.] Hanyang Univ, Dept Ophthalmol, Coll Med, Seoul 133791, South Korea. RP Sobrin, L (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Uveitis & Retina Serv, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu NR 15 TC 1 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 EI 1477-0962 J9 LUPUS JI Lupus PD APR PY 2014 VL 23 IS 4 BP 412 EP 416 DI 10.1177/0961203314522339 PG 5 WC Rheumatology SC Rheumatology GA AI9WS UT WOS:000337296000011 PM 24500485 ER PT J AU McKinlay, JB Trachtenberg, F Marceau, LD Katz, JN Fischer, MA AF McKinlay, John B. Trachtenberg, Felicia Marceau, Lisa D. Katz, Jeffrey N. Fischer, Michael A. TI Effects of Patient Medication Requests on Physician Prescribing Behavior Results of A Factorial Experiment SO MEDICAL CARE LA English DT Article DE direct to consumer; patient activation; disparities ID PRIMARY-CARE; CONSUMER; IMPACT AB Background: Because of internet searches, advice from friends, and pharmaceutical advertising, especially direct-to-consumer advertising, patients are increasingly activated to request medications during a physician encounter. Objectives: To estimate the effect of patient requests for medications on physician-prescribing behavior, unconfounded by patient, physician, and practice-setting factors. Research Design: Two experiments were conducted among 192 primary care physicians, each using different video-based scenarios: an undiagnosed "patient" with symptoms strongly suggesting sciatica, and a "patient" with already diagnosed chronic knee osteoarthritis. Half of patients with sciatica symptoms requested oxycodone, whereas the other half requested something to help with pain. Similarly, half of knee osteoarthritis patients specifically requested celebrex and half requested something to help with pain. Subjects: To increase generalizability and ensure sufficient numbers were available, we recruited 192 primary care physicians from 6 US states. Measures: The primary outcome was whether physicians would accede to a patient's request for a medication. Alternative pain medications prescribed were secondary outcomes. Results: 19.8% of sciatica patients requesting oxycodone would receive a prescription for oxycodone, compared with 1% of those making no specific request (P = 0.001). Fifty-three percent of knee osteoarthritis patients requesting celebrex would receive it, compared with 24% of patients making no request (P = 0.001). Patients requesting oxycodone were more likely to receive a strong narcotic (P = 0.001) and less likely to receive a weak narcotic (P = 0.01). Patients requesting celebrex were much less likely to receive a nonselective nonsteroidal anti-inflammatory drugs (P = 0.008). No patient attributes, physician, or organizational factors influenced a physician's willingness to accede to a patient's medication request. Conclusions: In both scenarios, activated patient requests for a medication substantially affected physician-prescribing decisions, despite the drawbacks of the requested medications. C1 [McKinlay, John B.; Trachtenberg, Felicia; Marceau, Lisa D.] New England Res Inst, Watertown, MA 02472 USA. [McKinlay, John B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med, Boston, MA USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Dept Orthoped Surg, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fischer, Michael A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP McKinlay, JB (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM jmckinlay@neriscience.com FU National Institute of Arthritis and Musculoskeletal and Skin Disorders (NIAMS) (NIH) [AR056992]; CVS-Caremark for studies of medication adherence FX Supported by Award Number AR056992 from the National Institute of Arthritis and Musculoskeletal and Skin Disorders (NIAMS) (NIH).; Dr Fischer has received research support from CVS-Caremark for studies of medication adherence. All other authors attest that they have no financial interest conflicting with complete and accurate reporting of the study findings. NR 18 TC 13 Z9 13 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2014 VL 52 IS 4 BP 294 EP 299 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ0AC UT WOS:000337309800004 PM 24848203 ER PT J AU Hausmann, LRM Gao, S Mor, MK Schaefer, JH Fine, MJ AF Hausmann, Leslie R. M. Gao, Shasha Mor, Maria K. Schaefer, James H., Jr. Fine, Michael J. TI Patterns of Sex and Racial/Ethnic Differences in Patient Health Care Experiences in US Veterans Affairs Hospitals SO MEDICAL CARE LA English DT Article DE sex; race and ethnicity; HCAHPS; health care experiences; veterans ID MEDICAID MANAGED CARE; ETHNIC DISPARITIES; PATIENTS PERCEPTIONS; INPATIENT CARE; UNITED-STATES; SATISFACTION; ASSESSMENTS; RACE/ETHNICITY; PROVIDERS AB Background: Few studies have assessed sex or racial/ethnic differences in inpatient experiences in the Veterans Affairs (VA) Healthcare System. Objectives: This study aimed to compare inpatient experiences by sex and race/ethnicity within and between VA hospitals. Research Design: We used mixed-effects multinomial regression to assess within-facility and between-facility sex and racial/ethnic differences in the 2010 VA Survey of Healthcare Experiences of Patients. Subjects: 50,471 respondents from 144 VA hospitals (4.5% female; 75.4% non-Hispanic white, 14.7% non-Hispanic black, 5.4% Hispanic, and 4.4% other race/ethnicity). Measures: Negative and positive patient-reported experiences in 13 health care domains were included. Results: Adjusted within-facility sex differences indicated that women reported more negative and less positive experiences than men in 4 domains, and less negative and more positive experiences on domains related to noise and privacy. Patients at facilities with more female patients reported more negative and less positive experiences in 4 domains. Blacks and Hispanics reported less negative and/or more positive experiences than whites within the same facility, although patients at facilities with more black and Hispanic patients reported more negative and less positive experiences overall. There were few and inconsistent within-facility differences between other racial/ethnic patients and whites. Patients at facilities with more other racial/ethnic patients reported slightly less negative and more positive experiences. Conclusions: Male, black, and Hispanic patients treated in VA hospitals tend to report more positive experiences than female and white patients treated at the same facilities. However, less positive experiences are reported by patients overall in hospitals that serve larger populations of women and racial/ethnic minorities. C1 [Hausmann, Leslie R. M.; Gao, Shasha; Mor, Maria K.; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hausmann, Leslie R. M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Schaefer, James H., Jr.] Off Informat & Analyt, Dept Vet Affairs, Durham, NC USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot CHERP, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM leslie.hausmann@gmail.com FU Center for Health Equity Research and Promotion (CHERP) VISN4 Pilot Research Program [LIP 72-056]; Veterans Affairs Health Services Research and Development Career Development Program [RCD 06-287] FX Supported by the Center for Health Equity Research and Promotion (CHERP) VISN4 Pilot Research Program (LIP 72-056). L.R.M.H.'s effort was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287). The views expressed here are those of the authors and do not represent those of the Department of Veterans Affairs or the United States Government. NR 27 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2014 VL 52 IS 4 BP 328 EP 335 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ0AC UT WOS:000337309800009 PM 24848206 ER PT J AU Ko, CW Dominitz, JA Neradilek, M Polissar, N Green, P Kreuter, W Baldwin, LM AF Ko, Cynthia W. Dominitz, Jason A. Neradilek, Moni Polissar, Nayak Green, Pam Kreuter, William Baldwin, Laura-Mae TI Determination of Colonoscopy Indication From Administrative Claims Data SO MEDICAL CARE LA English DT Article DE colonoscopy; health services research; electronic health records; algorithms ID COLORECTAL-CANCER; UNITED-STATES; ENDOSCOPY AB Background: Colonoscopy outcomes, such as polyp detection or complication rates, may differ by procedure indication. Objectives: To develop methods to classify colonoscopy indications from administrative data, facilitating study of colonoscopy quality and outcomes. Research Design: We linked 14,844 colonoscopy reports from the Clinical Outcomes Research Initiative, a national repository of endoscopic reports, to the corresponding Medicare Carrier and Outpatient File claims. Colonoscopy indication was determined from the procedure reports. We developed algorithms using classification and regression trees and linear discriminant analysis (LDA) to classify colonoscopy indication. Predictor variables included ICD-9CM and CPT/HCPCS codes present on the colonoscopy claim or in the 12 months prior, patient demographics, and site of colonoscopy service. Algorithms were developed on a training set of 7515 procedures, then validated using a test set of 7329 procedures. Results: Sensitivity was lowest for identifying average-risk screening colonoscopies, varying between 55% and 86% for the different algorithms, but specificity for this indication was consistently over 95%. Sensitivity for diagnostic colonoscopy varied between 77% and 89%, with specificity between 55% and 87%. Algorithms with classification and regression trees with 7 variables or LDA with 10 variables had similar overall accuracy, and generally lower accuracy than the algorithm using LDA with 30 variables. Conclusions: Algorithms using Medicare claims data have moderate sensitivity and specificity for colonoscopy indication, and will be useful for studying colonoscopy quality in this population. Further validation may be needed before use in alternative populations. C1 [Ko, Cynthia W.; Dominitz, Jason A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Neradilek, Moni; Polissar, Nayak] Mt Whisper Light Stat, Seattle, WA USA. [Green, Pam; Baldwin, Laura-Mae] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Kreuter, William] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Ko, CW (reprint author), Univ Washington, Div Gastroenterol, Box 356424, Seattle, WA 98195 USA. EM cwko@u.washington.edu FU NIH [CA127659]; American Society for Gastrointestinal Endoscopy Endoscopic Research Career Development Award; VA Puget Sound Health Care System, Department of Veterans Affairs FX Supported by NIH grant CA127659. J.A.D. was supported by the American Society for Gastrointestinal Endoscopy Endoscopic Research Career Development Award. This material is based upon work supported in part by the VA Puget Sound Health Care System, Department of Veterans Affairs. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 16 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD APR PY 2014 VL 52 IS 4 BP E21 EP E29 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ0AC UT WOS:000337309800001 PM 22437619 ER PT J AU Scott, SA Lubitz, SA AF Scott, Stuart A. Lubitz, Steven A. TI Warfarin pharmacogenetic trials: is there a future for pharmacogenetic-guided dosing? SO PHARMACOGENOMICS LA English DT Editorial Material DE clinical utility; CYP2C9; pharmacogenetics; pharmacogenomics; randomized controlled clinical trial; VKORC1; warfarin ID RANDOMIZED-TRIAL; AMERICAN-COLLEGE; THERAPY; ASSOCIATION; INITIATION; CYP2C9 C1 [Scott, Stuart A.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Scott, SA (reprint author), Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, One Gustave L Levy Pl,Box 1497, New York, NY 10029 USA. EM stuart.scott@mssm.edu FU NHLBI NIH HHS [K23 HL114724, K23HL114724]; NIGMS NIH HHS [K23 GM104401, K23GM104401] NR 19 TC 9 Z9 9 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2014 VL 15 IS 6 BP 719 EP 722 DI 10.2217/PGS.14.18 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI9BC UT WOS:000337220200001 PM 24897277 ER PT J AU Brunet, A Thomas, E Saumier, D Ashbaugh, AR Azzoug, A Pitman, RK Orr, SP Tremblay, J AF Brunet, Alain Thomas, Emilie Saumier, Daniel Ashbaugh, Andrea R. Azzoug, Abdelmadjid Pitman, Roger K. Orr, Scott P. Tremblay, Jacques TI Trauma Reactivation Plus Propranolol Is Associated With Durably Low Physiological Responding During Subsequent Script-Driven Traumatic Imagery SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE posttraumatic stress disorder; treatment; reconsolidation; memory; propranolol; traumatic stress ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOPHYSIOLOGICAL ASSESSMENT; COMBAT VETERANS; RECONSOLIDATION; PTSD; MEMORY; SCALE AB Objective: In a previous, double-blind, placebo-controlled study, patients with posttraumatic stress disorder (PTSD) showed lower physiological response during script-driven traumatic imagery 1 week after receiving a single dose of propranolol given after the retrieval of a traumatic memory. We hypothesized that this effect would extend beyond 1 week using a modified treatment approach. Method: Twenty-eight participants with PTSD read an account of their traumatic event once weekly for 6 consecutive weeks under the influence of open-label propranolol. One week and 4-months later, skin conductance, heart rate, and left corrugator electromyogram responses were measured while participants engaged in script-driven mental imagery of their traumatic event. Results from the 22 study participants were compared with results from treated and untreated participants in a previously published trial. Results: Most participants in our study were classified as non-PTSD cases at posttreatment and follow-up according to a psychophysiological discriminant function analysis. Posttreatment skin conductance and heart rate responses of the current (propranolol-treated) participants were lower than those of placebo participants from the previous study. No difference was observed between physiological responding measured posttreatment and at follow-up. Conclusions: Low physiological responding during script-driven traumatic imagery after treatment extends up to 4 months, demonstrating the durability of the treatment effect's. Limitations include the absence of a placebo-controlled group and lack of physiological baseline measures. Despite these limitations, results point to the need for future trials examining the clinical efficacy of trauma reactivation plus propranolol, as it has the potential to become a novel, cost- and time-effective treatment for PTSD. C1 [Brunet, Alain] Douglas Mental Hlth Univ Inst, Psychosocial Res Div, Montreal, PQ, Canada. [Brunet, Alain; Saumier, Daniel; Tremblay, Jacques] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Thomas, Emilie] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. [Saumier, Daniel; Azzoug, Abdelmadjid; Tremblay, Jacques] Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada. [Saumier, Daniel] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. [Ashbaugh, Andrea R.] Univ Ottawa, Sch Psychol, Ottawa, ON K1N 6N5, Canada. [Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. RP Brunet, A (reprint author), Douglas Inst Res Ctr, 6875 Lasalle Blvd, Montreal, PQ H4H 1R3, Canada. EM alain.brunet@mcgill.ca FU Fonds de recherche du Quebec; United States Army FX Dr Brunet, Dr Ashbaugh, and Ms Thomas received financial support from the Fonds de recherche du Quebec while working on this project. Dr Orr received a grant from the United States Army, which supported this study and other projects of which this study was a component. NR 22 TC 12 Z9 12 U1 9 U2 22 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD APR PY 2014 VL 59 IS 4 BP 228 EP 232 PG 5 WC Psychiatry SC Psychiatry GA AI6CH UT WOS:000336956900008 PM 25007116 ER PT J AU Oreskovic, NM Goodman, E Robinson, AI Perrin, EM Perrin, JM AF Oreskovic, Nicolas M. Goodman, Elizabeth Robinson, Alyssa I. Perrin, Eliana M. Perrin, James M. TI Adolescent Report of Lifestyle Counseling SO CHILDHOOD OBESITY LA English DT Article ID PHYSICAL-ACTIVITY QUESTIONNAIRE; CARDIOVASCULAR RISK; CHILDREN; OVERWEIGHT; OBESITY; PREVENTION; YOUTH AB Background: Physician counseling on lifestyle factors has been recommended as one way to help combat the obesity epidemic in the United States. The aim of this study was to examine the frequency of lifestyle counseling among healthy weight, overweight, and obese adolescents and determine the contributions of adolescent weight and physical activity. Methods: Self-reported surveys on dietary and physical activity counseling, along with measured height, weight, and physical activity data by accelerometry were collected on 76 adolescents ages 11-14 years. General linear models tested for associations of reported lifestyle counseling by weight category, adjusting for physical activity, age, gender, race/ethnicity, and parent education. Results: Half (47%) of the subjects were overweight or obese. Frequency of lifestyle counseling varied by weight category, with obese adolescents reporting greater amounts of lifestyle counseling across all topics than their peers. Obese adolescents received more dietary (beta = 0.88; standard error [SE] = 0.25; p = 0.001) and physical activity (beta = 0.80; SE = 0.28; p = 0.006) counseling than healthy weight youth, as well as being told to increase their physical activity more often (beta = 0.96; SE = 0.29; p = 0.001). There were no differences in lifestyle counseling between overweight and healthy weight subjects. Adolescents with greater daily moderate-to-vigorous physical activity reported less physical activity counseling (beta = -0.02; SE = 0.008; p = 0.05). Conclusions: Despite universal recommendations to counsel adolescents on lifestyle, only obese adolescents consistently report receiving such counseling. Given known difficulties in reversing obesity after onset, efforts should ensure that all adolescents receive lifestyle counseling. C1 [Oreskovic, Nicolas M.; Goodman, Elizabeth; Robinson, Alyssa I.; Perrin, James M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Goodman, Elizabeth; Perrin, James M.] MassGeneral Hosp Children, Dept Pediat, Boston, MA USA. [Oreskovic, Nicolas M.; Goodman, Elizabeth; Perrin, James M.] Harvard Univ, Sch Med, Boston, MA USA. [Perrin, Eliana M.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM noreskovic@partners.org OI Oreskovic, Nicolas/0000-0001-8702-8636 FU National Institutes of Health/National Heart, Lung, and Blood Institute [5K23HL103841]; Boston Nutrition Obesity Research Center FX All phases of this study were supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (5K23HL103841; principal investigator, N.M.O.). The study was also funded by a grant to Dr. Oreskovic from the Boston Nutrition Obesity Research Center. NR 25 TC 2 Z9 2 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-2168 EI 2153-2176 J9 CHILD OBES JI Child Obes. PD APR PY 2014 VL 10 IS 2 BP 107 EP 113 DI 10.1089/chi.2013.0131 PG 7 WC Pediatrics SC Pediatrics GA AI5GD UT WOS:000336892500004 PM 24617855 ER PT J AU Vandrey, R Babson, KA Herrmann, ES Bonn-Miller, MO AF Vandrey, Ryan Babson, Kimberly A. Herrmann, Evan S. Bonn-Miller, Marcel O. TI Interactions between disordered sleep, post-traumatic stress disorder, and substance use disorders SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID ALCOHOL-DEPENDENT INDIVIDUALS; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; CHRONIC COCAINE USERS; DOUBLE-BLIND; MARIJUANA WITHDRAWAL; COMBAT VETERANS; CANNABIS USE; SMOKING-CESSATION; IMAGERY REHEARSAL AB Disordered sleep is associated with a number of adverse health consequences and is an integral component of many psychiatric disorders. Rates of substance use disorders (SUDs) are markedly higher among individuals with post-traumatic stress disorder (PTSD), and this relationship may be partly mediated by disturbed sleep. Sleep disturbances (e. g. insomnia, daytime sleepiness, vivid nightmares) are hallmark features of PTSD and there is evidence that individuals with PTSD engage in substance use as a means of coping with these symptoms. However, prolonged substance use can lead to more severe sleep disturbances due to the development of tolerance and withdrawal. Behavioural or pharmacological treatment of disordered sleep is associated with improved daytime symptoms and psychosocial functioning among individuals who have developed PTSD. Initial research also suggests that improving sleep could be similarly beneficial in reducing coping oriented substance use and preventing relapse among those seeking treatment for SUDs. Together, these findings suggest that ameliorating sleep disturbance among at-risk individuals would be a viable target for the prevention and treatment of PTSD and associated SUDs, but prospective research is needed to examine this hypothesis. Enhanced understanding of the interrelation between sleep, PTSD, and SUDs may yield novel prevention and intervention approaches for these costly, prevalent and frequently co-occurring disorders. C1 [Vandrey, Ryan; Herrmann, Evan S.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Palo Alto, CA USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Babson, Kimberly A.] Stanford Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA. [Bonn-Miller, Marcel O.] Philadelphia Vet Affairs Med Ctr, Ctr Excellence Substance Abuse Treatment & Educ, Philadelphia, PA USA. [Bonn-Miller, Marcel O.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Vandrey, R (reprint author), Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, 5510 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rvandrey@jhmi.edu OI Babson, Kimberly/0000-0002-9233-8230 FU NIDA NIH HHS [U01-DA031784, T32-DA07209, U01 DA031784, T32 DA007209] NR 141 TC 10 Z9 10 U1 3 U2 15 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0954-0261 EI 1369-1627 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD APR PY 2014 VL 26 IS 2 BP 237 EP 247 DI 10.3109/09540261.2014.901300 PG 11 WC Psychiatry SC Psychiatry GA AI6XB UT WOS:000337019200009 PM 24892898 ER PT J AU Grady, D Redberg, RF Mallon, WK AF Grady, Deborah Redberg, Rita F. Mallon, William K. TI How Should Top-Five Lists Be Developed? What Is the Next Step? SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Grady, Deborah; Redberg, Rita F.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Mallon, William K.] Univ So Calif, Keck Sch Med, Dept Clin Emergency Med, Los Angeles, CA 90033 USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. NR 1 TC 7 Z9 7 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 498 EP 499 DI 10.1001/jamainternmed.2013.8272 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900004 PM 24534809 ER PT J AU Aldridge, MD Schlesinger, M Barry, CL Morrison, RS McCorkle, R Hurzeler, R Bradley, EH AF Aldridge, Melissa D. Schlesinger, Mark Barry, Colleen L. Morrison, R. Sean McCorkle, Ruth Huerzeler, Rosemary Bradley, Elizabeth H. TI National Hospice Survey Results For-Profit Status, Community Engagement, and Service SO JAMA INTERNAL MEDICINE LA English DT Article ID FAMILY-MEMBERS; NURSING-HOME; CARE; ENROLLMENT; OWNERSHIP; NONPROFIT; PATTERNS; INDUSTRY; LIFE; END AB IMPORTANCE The impact of the substantial growth in for-profit hospices in the United States on quality and hospice access has been intensely debated, yet little is known about how for-profit and nonprofit hospices differ in activities beyond service delivery. OBJECTIVE To determine the association between hospice ownership and (1) provision of community benefits, (2) setting and timing of the hospice population served, and (3) community outreach. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional survey (the National Hospice Survey), conducted from September 2008 through November 2009, of a national random sample of 591 Medicare-certified hospices operating throughout the United States. EXPOSURES For-profit or nonprofit hospice ownership. MAIN OUTCOMES AND MEASURES Provision of community benefits; setting and timing of the hospice population served; and community outreach. RESULTS A total of 591 hospices completed our survey (84% response rate). For-profit hospices were less likely than nonprofit hospices to provide community benefits including serving as training sites (55% vs 82%; adjusted relative risk [ARR], 0.67 [95% CI, 0.59-0.76]), conducting research (18% vs 23%; ARR, 0.67 [95% CI, 0.46-0.99]), and providing charity care (80% vs 82%; ARR, 0.88 [95% CI, 0.80-0.96]). For-profit compared with nonprofit hospices cared for a larger proportion of patients with longer expected hospice stays including those in nursing homes (30% vs 25%; P =.009). For-profit hospices were more likely to exceed Medicare's aggregate annual cap (22% vs 4%; ARR, 3.66 [95% CI, 2.02-6.63]) and had a higher patient disenrollment rate (10% vs 6%; P <.001). For-profit were more likely than nonprofit hospices to engage in outreach to low-income communities (61% vs 46%; ARR, 1.23 [95% CI, 1.05-1.44]) and minority communities (59% vs 48%; ARR, 1.18 [95% CI, 1.02-1.38]) and less likely to partner with oncology centers (25% vs 33%; ARR, 0.59 [95% CI, 0.44-0.80]). CONCLUSIONS AND RELEVANCE Ownership-related differences are apparent among hospices in community benefits, population served, and community outreach. Although Medicare's aggregate annual cap may curb the incentive to focus on long-stay hospice patients, additional regulatory measures such as public reporting of hospice disenrollment rates should be considered as the share of for-profit hospices in the United States continues to increase. C1 [Aldridge, Melissa D.; Morrison, R. Sean] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Schlesinger, Mark; McCorkle, Ruth; Bradley, Elizabeth H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Morrison, R. Sean] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Huerzeler, Rosemary] John Thompson Hosp Inst Educ Training & Res Inc, Branford, CT USA. RP Aldridge, MD (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,POB 1070, New York, NY 10029 USA. EM Melissa.Aldridge@mssm.edu FU National Cancer Institute [1R01CA116398-01A2]; John D. Thompson Foundation; National Institute of Nursing Research [1K99NR010495-01] FX This study was supported by grant 1R01CA116398-01A2 from the National Cancer Institute (Dr Bradley); the John D. Thompson Foundation (Dr Bradley); and grant 1K99NR010495-01 from the National Institute of Nursing Research (Dr Aldridge). NR 28 TC 11 Z9 11 U1 7 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 500 EP 506 DI 10.1001/jamainternmed.2014.3 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900005 PM 24567076 ER PT J AU Schuur, JD Carney, DP Lyn, ET Raja, AS Michael, JA Ross, NG Venkatesh, AK AF Schuur, Jeremiah D. Carney, Dylan P. Lyn, Everett T. Raja, Ali S. Michael, John A. Ross, Nicholas G. Venkatesh, Arjun K. TI A Top-Five List for Emergency Medicine A Pilot Project to Improve the Value of Emergency Care SO JAMA INTERNAL MEDICINE LA English DT Article ID HEALTH-CARE; METHODOLOGY; RADIOGRAPHY; GUIDELINES; INJURY; TRAUMA AB IMPORTANCE The mean cost of medical care in the United States is growing at an unsustainable rate; from 2003 through 2011, the cost for an emergency department (ED) visit rose 240%, from $560 to $1354. The diagnostic tests, treatments, and hospitalizations that emergency clinicians order result in significant costs. OBJECTIVE To create a "top-five" list of tests, treatments, and disposition decisions that are of little value, are amenable to standardization, and are actionable by emergency medicine clinicians. DESIGN, SETTING, AND PARTICIPANTS Modified Delphi consensus process and survey of 283 emergency medicine clinicians (physicians, physician assistants, and nurse practitioners) from 6 EDs. INTERVENTION We assembled a technical expert panel (TEP) and conducted a modified Delphi process to identify a top-five list using a 4-step process. In phase 1, we generated a list of low-value clinical decisions from TEP brainstorming and e-mail solicitation of clinicians. In phase 2, the TEP ranked items on contribution to cost, benefit to patients, and actionability by clinicians. In phase 3, we surveyed all ordering clinicians from the 6 EDs regarding distinct aspects of each item. In phase 4, the TEP voted for a final top-five list based on survey results and discussion. MAIN OUTCOMES AND MEASURES A top-five list for emergency medicine. The TEP ranked items on contribution to cost, benefit to patients, and actionability by clinicians. The survey asked clinicians to score items on the potential benefit or harm to patients and the provider actionability of each item. Voting and surveys used 5-point Likert scales. A Pearson interdomain correlation was used. RESULTS Phase 1 identified 64 low-value items. Phase 2 narrowed this list to 7 laboratory tests, 3 medications, 4 imaging studies, and 3 disposition decisions included in the phase 3 survey (71.0% response rate). All 17 items showed a significant positive correlation between benefit and actionability (r. 0.19-0.37 [P <= .01]). One item received unanimous TEP support, 4 received majority support, and 12 received at least 1 vote. CONCLUSIONS AND RELEVANCE Our TEP identified clinical actions that are of low value and within the control of ED health care providers. This method can be used to identify additional actionable targets of overuse in emergency medicine. C1 [Schuur, Jeremiah D.; Raja, Ali S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Schuur, Jeremiah D.; Raja, Ali S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Carney, Dylan P.; Venkatesh, Arjun K.] Harvard Univ, Sch Med, Boston, MA USA. [Lyn, Everett T.; Michael, John A.; Ross, Nicholas G.] North Shore Med Ctr, Dept Emergency Med, Salem, MA USA. [Raja, Ali S.] Brigham & Womens Hosp, Ctr Evidence Based Imaging, Boston, MA 02115 USA. [Venkatesh, Arjun K.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schuur, JD (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM jschuur@partners.org FU Emergency Medicine Residents' Association student research grant FX This study was supported by an Emergency Medicine Residents' Association student research grant (Mr Carney). NR 19 TC 31 Z9 31 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 509 EP 515 DI 10.1001/jamainternmed.2013.12688 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900007 PM 24534899 ER PT J AU Billings, JA Bernacki, R AF Billings, J. Andrew Bernacki, Rachelle TI Strategic Targeting of Advance Care Planning Interventions The Goldilocks Phenomenon SO JAMA INTERNAL MEDICINE LA English DT Article ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; CODE STATUS DOCUMENTATION; TERMINALLY-ILL PATIENTS; NURSING-HOME RESIDENTS; SEATTLE HEART-FAILURE; OLDER-ADULTS; ELDERLY-PATIENTS; SUSTAINING TREATMENT; SURPRISE QUESTION AB Strategically selecting patients for discussions and documentation about limiting life-sustaining treatments-choosing the right time along the end-of-life trajectory for such an intervention and identifying patients at high risk of facing end-of-life decisions-can have a profound impact on the value of advance care planning (ACP) efforts. Timing is important because the completion of an advance directive (AD) too far from or too close to the time of death can lead to end-of-life decisions that do not optimally reflect the patient's values, goals, and preferences: a poorly chosen target patient population that is unlikely to need an AD in the near future may lead to patients making unrealistic, hypothetical choices, while assessing preferences in the emergency department or hospital in the face of a calamity is notoriously inadequate. Because much of the currently studied ACP efforts have led to a disappointingly small proportion of patients eventually benefitting from an AD, careful targeting of the intervention should also improve the efficacy of such projects. A key to optimal timing and strategic selection of target patients for an ACP program is prognostication, and we briefly highlight prognostication tools and studies that may point us toward high-value AD interventions. C1 [Billings, J. Andrew] Cambridge Hlth Alliance, Boston, MA USA. [Billings, J. Andrew] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bernacki, Rachelle] Dana Farber Canc Ctr, Dept Psychosocial Oncol & Palliat Care, Boston, MA USA. [Bernacki, Rachelle] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Bernacki, Rachelle] Ariadne Labs, Boston, MA USA. [Billings, J. Andrew; Bernacki, Rachelle] Harvard Univ, Sch Med, Ctr Palliat Care, Cambridge, MA 02138 USA. RP Billings, JA (reprint author), Harvard Univ, Sch Med, Ctr Palliat Care, 11 1-2 Hilliard St, Cambridge, MA 02138 USA. EM jbillings@partners.org FU Health Resources and Services Administration [1K01 HP 20462] FX Dr Bernacki is supported by grant 1K01 HP 20462 from the Health Resources and Services Administration. NR 60 TC 17 Z9 17 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 620 EP 624 DI 10.1001/jamainternmed.2013.14384 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900027 PM 24493203 ER PT J AU Thomas, HN Chang, CCH Dillon, S Hess, R AF Thomas, Holly N. Chang, Chung-Chou H. Dillon, Stacey Hess, Rachel TI Sexual Activity in Midlife Women: Importance of Sex Matters SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Thomas, Holly N.; Chang, Chung-Chou H.; Dillon, Stacey; Hess, Rachel] Univ Pittsburgh, Ctr Res Healthcare, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Thomas, Holly N.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Thomas, HN (reprint author), Univ Pittsburgh, Ctr Res Healthcare, Div Gen Internal Med, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. EM thomashn@upmc.edu FU NIA NIH HHS [AG024254] NR 5 TC 12 Z9 12 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 631 EP + DI 10.1001/jamainternmed.2013.14402 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900030 PM 24515395 ER PT J AU Dhaliwal, G AF Dhaliwal, Gurpreet TI "Expert Opinion" Software for Medical Diagnosis and Treatment Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94131 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Dhaliwal, G (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, 4150 Clement St 111, San Francisco, CA 94131 USA. EM gurpreet.dhaliwal@ucsf.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 639 EP 640 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900037 PM 24711185 ER PT J AU Singh, H Meyer, AND AF Singh, Hardeep Meyer, Ashley N. D. TI "Expert Opinion" Software for Medical Diagnosis and Treatment Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Singh, Hardeep; Meyer, Ashley N. D.] Michael E DeBakey VA Med Ctr, Houston VA Hlth Serv Res & Dev, Ctr Innovat Qual Effectiveness & Safety, Houston, TX USA. [Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 639 EP 639 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900036 PM 24711184 ER PT J AU Jackevicius, CA Krumholz, HM AF Jackevicius, Cynthia A. Krumholz, Harlan M. TI Role of Nicotinic Acid in Atherosclerosis Prevention Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID NIACIN; THERAPY C1 [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA 91766 USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Krumholz, Harlan M.] Sect Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, New Haven, CT USA. [Krumholz, Harlan M.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E Second St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR PY 2014 VL 174 IS 4 BP 649 EP 649 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AI4NK UT WOS:000336841900053 PM 24711201 ER PT J AU Friedman, DJ Wang, N Meigs, JB Hoffmann, U Massaro, JM Fox, CS Magnani, JW AF Friedman, Daniel J. Wang, Na Meigs, James B. Hoffmann, Udo Massaro, Joseph M. Fox, Caroline S. Magnani, Jared W. TI Pericardial Fat is Associated With Atrial Conduction: The Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrium; conduction; electrocardiography; epidemiology; obesity ID EPICARDIAL ADIPOSE-TISSUE; BODY-MASS INDEX; ATHEROSCLEROSIS RISK; INTRATHORACIC FAT; OBESE SUBJECTS; FIBRILLATION; HEALTH; COMMUNITIES; PREVALENCE; MORPHOLOGY AB Background-Obesity is associated with altered atrial electrophysiology and a prominent risk factor for atrial fibrillation. Body mass index, the most widely used adiposity measure, has been related to atrial electrical remodeling. We tested the hypothesis that pericardial fat is independently associated with electrocardiographic measures of atrial conduction. Methods and Results-We performed a cross-sectional analysis of 1946 Framingham Heart Study participants (45% women) to determine the relation between pericardial fat and atrial conduction as measured by P wave indices (PWI): PR interval, P wave duration (P-duration), P wave amplitude (P-amplitude), P wave area (P-area), and P wave terminal force (P-terminal). We performed sex-stratified linear regression analyses adjusted for relevant clinical variables and ectopic fat depots. Each 1-SD increase in pericardial fat was significantly associated with PR interval (beta=1.7 ms, P=0.049), P-duration (beta=2.3 ms, P<0.001), and P-terminal (beta=297 mu V.ms, P<0.001) among women; and P-duration (beta=1.2 ms, P=0.002), P-amplitude (beta=-2.5 mu V, P<0. 001), and P-terminal (beta=160 mu V.ms, P=0.002) among men. Among both sexes, pericardial fat was significantly associated with P-duration in analyses additionally adjusting for visceral fat or intrathoracic fat; a similar but non-significant trend existed with P-terminal. Among women, pericardial fat was significantly associated with P wave area after adjustment for visceral and intrathoracic fat. Conclusions-Pericardial fat is associated with atrial conduction as quantified by PWI, even with adjustment for extracardiac fat depots. Further studies are warranted to identify the mechanisms through which pericardial fat may modify atrial electrophysiology and promote subsequent risk for arrhythmogenesis. C1 [Friedman, Daniel J.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Massaro, Joseph M.; Fox, Caroline S.; Magnani, Jared W.] NHLBI, Framingham, MA USA. [Massaro, Joseph M.; Fox, Caroline S.; Magnani, Jared W.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Magnani, Jared W.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sect Cardiovasc Med, Sch Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Friedman, Daniel /0000-0001-5791-1954 FU American Heart Association [09FTF219028]; Boston University School of Medicine Department of Medicine Career Investment Award; NIH [2K24 DK080140]; National Heart, Lung, and Blood Institute [R21HL1060926]; Framingham Heart Study contract [N01-HC25195] FX Dr Magnani is supported by American Heart Association award 09FTF219028 and a Boston University School of Medicine Department of Medicine Career Investment Award, and Dr Meigs by NIH grant 2K24 DK080140. This work was supported by National Heart, Lung, and Blood Institute grant R21HL1060926 and Framingham Heart Study contract N01-HC25195. NR 30 TC 11 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2014 VL 3 IS 2 AR e000477 DI 10.1161/JAHA.113.000477 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000012 PM 24595189 ER PT J AU Magnani, JW Yin, XY McManus, DD Chuang, ML Cheng, SS Lubitz, SA Arora, G Manning, WJ Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Yin, Xiaoyan McManus, David D. Chuang, Michael L. Cheng, Susan Lubitz, Steven A. Arora, Garima Manning, Warren J. Ellinor, Patrick T. Benjamin, Emelia J. TI Genetic Loci Associated With Atrial Fibrillation: Relation to Left Atrial Structure in the Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrial fibrillation; cohort studies; genetics; left atrium; single nucleotide polymorphism ID GENOME-WIDE ASSOCIATION; LONGITUDINAL TRACKING; CHROMOSOME 4Q25; COMMON VARIANTS; RISK SCORE; M-MODE; SUSCEPTIBILITY; COHORT; METAANALYSIS; COMMUNITY AB Background-Atrial fibrillation (AF) results in significant morbidity and mortality. Genome-wide association studies (GWAS) have identified genetic variants associated with AF. Whether genetic variants associated with AF are also associated with atrial structure, an intermediate phenotype for AF, has had limited investigation. We sought to investigate associations between single nucleotide polymorphisms (SNPs) and atrial structure obtained by cardiovascular imaging in the Framingham Heart Study. Methods and Results-We selected 11 SNPs that have been associated with AF in GWAS. We examined the SNPs' relations to cross-sectional left atrial (LA) dimensions (determined by transthoracic echocardiography) and LA volume (determined by cardiovascular magnetic resonance [CMR]) employing linear regression. The total sample included 1555 participants with CMR LA volume (age 60 +/- 9 years, 53% women) and 6861 participants with echocardiographic LA diameter (age 48 +/- 13 years, 52% women) measured. We employed a significance threshold of P<0.0023 to account for multiple testing of the 11 SNPs and 2 LA measures. In a primary analysis, no SNPs were significantly related to the LA measures. Likewise, in secondary analyses excluding individuals with prevalent AF (n=77, CMR sample; n=105, echocardiography sample) no SNPs were related to LA volume or diameter. Conclusion-In a community-based cohort, we did not identify a statistically significant association between selected SNPs associated with AF and measures of LA anatomy. Further investigations with larger longitudinally assessed samples and a broader array of SNPs may be necessary to determine the relation between genetic loci associated with AF and atrial structure. C1 [Magnani, Jared W.; Yin, Xiaoyan; McManus, David D.; Chuang, Michael L.; Cheng, Susan; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Magnani, Jared W.; Yin, Xiaoyan; McManus, David D.; Chuang, Michael L.; Cheng, Susan; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Yin, Xiaoyan] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [McManus, David D.] Univ Massachusetts, Dept Med, Cardiol Sect, Worcester, MA 01605 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Arora, Garima; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Arora, Garima; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Arora, Garima; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF219028, 13EIA14220013]; NIH [5R21HL106092, 2RO1HL092577, RC1-HL101056, 1R01HL102214, RO1 HL70279, 1RO1HL104156, 1K24HL105780, 6R01-NS17950, N01-HC25195]; Boston University School of Medicine Department of Medicine Career Investment Award FX This work was supported by grants from the American Heart Association (Award 09FTF219028) to Dr Magnani and (13EIA14220013) to Dr Ellinor, and from the NIH to Dr Magnani (5R21HL106092), Drs Benjamin and Ellinor (2RO1HL092577), Dr. Benjamin (RC1-HL101056, 1R01HL102214), Dr Manning (RO1 HL70279), and Dr Ellinor (1RO1HL104156, 1K24HL105780) and 6R01-NS17950, N01-HC25195. This work was further supported by a Boston University School of Medicine Department of Medicine Career Investment Award to Dr Magnani. NR 32 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2014 VL 3 IS 2 AR e000616 DI 10.1161/JAHA.113.000616 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000033 PM 24695651 ER PT J AU Piccini, JP Hellkamp, AS Lokhnygina, Y Patel, MR Harrell, FE Singer, DE Becker, RC Breithardt, G Halperin, JL Hankey, GJ Berkowitz, SD Nessel, CC Mahaffey, KW Fox, KAA Califf, RM AF Piccini, Jonathan P. Hellkamp, Anne S. Lokhnygina, Yuliya Patel, Manesh R. Harrell, Frank E., Jr. Singer, Daniel E. Becker, Richard C. Breithardt, Guenter Halperin, Jonathan L. Hankey, Graeme J. Berkowitz, Scott D. Nessel, Christopher C. Mahaffey, Kenneth W. Fox, Keith A. A. Califf, Robert M. CA ROCKET AF Investigators TI Relationship Between Time in Therapeutic Range and Comparative Treatment Effect of Rivaroxaban and Warfarin: Results From the ROCKET AF Trial SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE rivaroxaban; time in therapeutic range; warfarin ID NONVALVULAR ATRIAL-FIBRILLATION; NORMALIZED RATIO CONTROL; RE-LY TRIAL; ANTICOAGULATION CONTROL; STROKE PREVENTION; ORAL ANTICOAGULATION; OPTIMAL INTENSITY; METAANALYSIS; COUNTRIES; PHYSICIAN AB Background-Time in therapeutic range (TTR) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (cTTR) since such analysis preserves randomized comparisons. Methods and Results-TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio (INR) values performed during warfarin initiation. Measurements during warfarin interruptions >7 days were excluded. INRs were performed via standardized finger-stick point-of-care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non-central nervous system embolism) was examined by quartiles of cTTR and by cTTR as a continuous function. Centers with the highest cTTRs by quartile had lower-risk patients as reflected by lower CHADS(2) scores (P<0.0001) and a lower prevalence of prior stroke or transient ischemic attack (P<0.0001). Sites with higher cTTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of cTTRs (P value for interaction=0.71). The hazard of major and non-major clinically relevant bleeding increased with cTTR (P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold cTTR values. Conclusions-The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of cTTR. C1 [Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Becker, Richard C.; Mahaffey, Kenneth W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27705 USA. [Harrell, Frank E., Jr.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Breithardt, Guenter] Hosp Univ Munster, Munster, Germany. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Icahn Sch Med Mt Sinai, Cardiovasc Inst, New York, NY 10029 USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA 6001, Australia. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA. [Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27705 USA. EM jonathan.piccini@duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ); Bayer HealthCare AG (Leverkusen, Germany) FX Supported by research grants from Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ) and Bayer HealthCare AG (Leverkusen, Germany). NR 21 TC 26 Z9 27 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2014 VL 3 IS 2 AR e000521 DI 10.1161/JAHA.113.000521 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000039 PM 24755148 ER PT J AU Sherwood, MW Wiviott, SD Peng, SA Roe, MT DeLemos, J Peterson, ED Wang, TY AF Sherwood, Matthew W. Wiviott, Stephen D. Peng, S. Andrew Roe, Matthew T. DeLemos, James Peterson, Eric D. Wang, Tracy Y. TI Early Clopidogrel Versus Prasugrel Use Among Contemporary STEMI and NSTEMI Patients in the US: Insights From the National Cardiovascular Data Registry SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE myocardial infarction; P2Y12 antagonist; prasugrel ID ST-SEGMENT-ELEVATION; ACUTE CORONARY SYNDROMES; ASSOCIATION TASK-FORCE; SUPPRESS ADVERSE OUTCOMES; RAPID RISK STRATIFICATION; MYOCARDIAL-INFARCTION; PRACTICE GUIDELINES; EARLY IMPLEMENTATION; ACC/AHA GUIDELINES; CONTROLLED-TRIAL AB Background-P2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. Methods and Results-Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients >= 75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. Conclusions-With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio. C1 [Sherwood, Matthew W.; Peng, S. Andrew; Roe, Matthew T.; Peterson, Eric D.; Wang, Tracy Y.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA. [Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [DeLemos, James] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. RP Sherwood, MW (reprint author), Duke Clin Res Inst, 2400 Pratt St,POB 17969, Durham, NC 27705 USA. EM matthew.sherwood@dm.duke.edu FU Agency for Healthcare Research and Quality [U19HS021092] FX This project was supported in part by grant number U19HS021092 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. NR 36 TC 29 Z9 29 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2014 VL 3 IS 2 AR e000849 DI 10.1161/JAHA.114.000849 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000046 PM 24732921 ER PT J AU Sun, CHJ Ribo, M Goyal, M Yoo, AJ Jovin, T Cronin, CA Zaidat, O Nogueira, R Nguyen, T Hussain, MS Menon, BK Mehta, B Jindal, G Horev, A Norbash, A Leslie-Mazwi, T Wisco, D Gupta, R AF Sun, Chung-Huan J. Ribo, Marc Goyal, Mayank Yoo, Albert J. Jovin, Tudor Cronin, Carolyn A. Zaidat, Osama Nogueira, Raul Nguyen, Thanh Hussain, M. Shazam Menon, Bijoy K. Mehta, Brijesh Jindal, Gaurav Horev, Anat Norbash, Alexander Leslie-Mazwi, Thabele Wisco, Dolora Gupta, Rishi TI Door-to-Puncture: A Practical Metric for Capturing and Enhancing System Processes Associated With Endovascular Stroke Care, Preliminary Results From the Rapid Reperfusion Registry SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE endovascular treatment; ischemic; stroke; stroke delivery; stroke management ID ACUTE ISCHEMIC-STROKE; BALLOON TIME; MYOCARDIAL-INFARCTION; POOLED ANALYSIS; TRIAL; MORTALITY; REVASCULARIZATION; OUTCOMES; THERAPY; SAFETY AB Background-In 2011, the Brain Attack Coalition proposed door-to-treatment times of 2 hours as a benchmark for patients undergoing intra-arterial therapy (IAT). We designed the Rapid Reperfusion Registry to capture the percentage of stroke patients who meet the target and its impact on outcomes. Methods and Results-This is a retrospective analysis of anterior circulation patients treated with IAT within 9 hours of symptom onset. Data was collected from December 31, 2011 to December 31, 2012 at 2 centers and from July 1, 2012 to December 31, 2012 at 7 centers. Short "Door-to-Puncture" (D2P) time was hypothesized to be associated with good patient outcomes. A total of 478 patients with a mean age of 68 +/- 14 years and median National Institutes of Health Stroke Scale (NIHSS) of 18 (IQR 14 to 21) were analyzed. The median times for IAT delivery were 234 minutes (IQR 163 to 304) for "last known normal-to-groin puncture" time (LKN-to-GP) and 112 minutes (IQR 68 to 176) for D2P time. The overall good outcome rate was 39.7% for the entire cohort. In a multivariable model adjusting for age, NIHSS, hypertension, diabetes, reperfusion status, and symptomatic hemorrhage, both short LKN-to-GP (OR 0.996; 95% CI [0.993 to 0.998]; P<0.001) and short D2P times (OR 0.993, 95% CI [0.990 to 0.996]; P<0.001) were associated with good outcomes. Only 52% of all patients in the registry achieved the targeted D2P time of 2 hours. Conclusions-The time interval of D2P presents a clinically relevant time frame by which system processes can be targeted to streamline the delivery of IAT care nationally. At present, there is much opportunity to enhance outcomes through reducing D2P. C1 [Sun, Chung-Huan J.; Nogueira, Raul; Gupta, Rishi] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Ribo, Marc] Univ Autonoma Barcelona, Hosp Vall DHebron, Dept Neurol, Stroke Unit, E-08193 Barcelona, Spain. [Goyal, Mayank] Univ Calgary, Dept Radiol & Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Menon, Bijoy K.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB T2N 1N4, Canada. [Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Mehta, Brijesh; Leslie-Mazwi, Thabele] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Jovin, Tudor; Horev, Anat] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA USA. [Cronin, Carolyn A.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Jindal, Gaurav] Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA. [Zaidat, Osama] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Nguyen, Thanh] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Norbash, Alexander] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02118 USA. [Hussain, M. Shazam; Wisco, Dolora] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Gupta, Rishi] Kennestone Hosp, Wellstar Neurosurg, Marietta, GA USA. RP Gupta, R (reprint author), 61 Whitcher St,Suite 3110, Marietta, GA 30060 USA. EM guptar31@gmail.com RI Demchuk, Andrew/E-1103-2012 OI Demchuk, Andrew/0000-0002-4930-7789 FU Instituto de Salud Carlos III, Ministerio de Economia y Competitividad; Covidien EV3; National Institutes of Health; Remedy Pharmaceuticals; Silk Road Medical; Penumbra Inc FX Sun, none; Ribo, recipient of a grant from Instituto de Salud Carlos III, Ministerio de Economia y Competitividad; Goyal, Institutional grant for ESCAPE trial from Covidien EV3, Covidien EV3 for help with design and execution of SWIFT PRIME; Yoo, receives research funding from the National Institutes of Health, Penumbra Inc, and Remedy Pharmaceuticals; Jovin, Silk Road Medical; Cronin, none; Zaidat, penumbra, stryker, microvention, EV3, codman; Nogueira, Scientific advisory board for Stryker Neurovascular, Covidien, CoAxia. Serves on the Data Safety Monitoring Board for Rapid Medical and Imaging Core Lab for Covidien and Reverse Medical, Editor of Interventional Neurology; Nguyen, none; Hussain, none; Menon, none; Mehta, none; Jindal, none; Horev, none; Norbash, none; Leslie-Mazwi, none; Wisco, none; Gupta, scientific advisory board for Stryker Neurovascular, Covidien, CoAxia. Member of the Data Safety Monitoring Board for Reverse Medical and Rapid Medical; Associate Editor for the Journal of Neuroimaging, Associate Editor for Interventional Neurology, and Associate Editor for the Journal of Neurointerventional Surgery. NR 25 TC 17 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2014 VL 3 IS 2 AR e000859 DI 10.1161/JAHA.114.000859 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI3XC UT WOS:000336798000050 PM 24772523 ER PT J AU Kochendorfer, L Bauer, P Funk, J Toteberg-Harms, M AF Kochendoerfer, L. Bauer, P. Funk, J. Toeteberg-Harms, M. TI Posterior Pole Asymmetry Analysis with Optical Coherence Tomography SO KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE LA English DT Article DE optical coherence tomography; spectral-domain optical coherence tomography; SD-OCT; spectralis OCT; OCT; reproducibility; glaucoma; posterior pole asymmetry analysis ID FIBER LAYER THICKNESS; SPECTRAL-DOMAIN; RETINAL-THICKNESS; GLAUCOMATOUS EYES; REPRODUCIBILITY; OCT AB Background: The aim of this study was to evaluate the reproducibility of the posterior pole asymmetry analysis (PPAA) in glaucomatous eyes and healthy controls in comparison to retinal nerve fiber layer measurements (RNFL) with spectral domain optical coherence tomography (SD-OCT). Patients and Methods: Prospectively, in a single session by one operator, three measurements were taken of the retinal thickness with the PPAA and three measurements of the RNFL with the eye-tracker function of the Heidelberg Spectralis SD-OCT. Results: The mean intraclass correlation coefficient (ICC) and lower confidence intervals (in parentheses) for PPAA were 0.98 (0.96) in both healthy (36 eyes) and glaucomatous eyes (26 eyes). Global coefficients of variation (COVs) were between 0.0 and 1.1% in healthy controls and between 0.0 and 1.9% in glaucoma eyes. Global ICCs for RNFL were 0.98 (0.96) in healthy controls and 0.98 (0.97) in glaucoma eyes and global COVs were between 0.0 and 6.8% in healthy controls and between 0.0 and 3.0% in glaucoma eyes. Conclusion: Reproducibility of the PPAA was good and exceeds that of established RNFL measurements. Thus, PPAA is an additional useful tool in management of glaucoma. C1 [Kochendoerfer, L.; Funk, J.; Toeteberg-Harms, M.] Univ Zurich Hosp, Dept Ophthalmol, CH-8091 Zurich, Switzerland. [Bauer, P.] Cantonal Hosp Winterthur, Dept Ophthalmol, Winterthur, Switzerland. [Toeteberg-Harms, M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Toteberg-Harms, M (reprint author), Univ Zurich Hosp, Dept Ophthalmol, Frauenklin Str 24, CH-8091 Zurich, Switzerland. EM MarcToeteberg@aol.com OI Toeteberg-Harms, Marc/0000-0002-2134-1336 FU Swiss National Science Foundation (SNSF) [PBZHP3_141457] FX M.T.-H. received personal funding by the Swiss National Science Foundation (SNSF Project No. PBZHP3_141457). The authors have no proprietary or commercial interest in any materials discussed in this article. NR 18 TC 4 Z9 4 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0023-2165 EI 1439-3999 J9 KLIN MONATSBL AUGENH JI Klinische Monatsblat. Augenheilkunde PD APR PY 2014 VL 231 IS 4 BP 368 EP 373 DI 10.1055/s-0034-1368213 PG 6 WC Ophthalmology SC Ophthalmology GA AI4PX UT WOS:000336848400028 PM 24771169 ER PT J AU Shtivelman, E Davies, MA Hwu, P Yang, J Lotem, M Oren, M Flaherty, KT Fisher, DE AF Shtivelman, Emma Davies, Michael A. Hwu, Patrick Yang, James Lotem, Michal Oren, Moshe Flaherty, Keith T. Fisher, David E. TI Pathways and therapeutic targets in melanoma SO ONCOTARGET LA English DT Review DE melanoma; targeted therapy; immune therapy ID CIRCULATING TUMOR-CELLS; PHASE-II TRIAL; CUTANEOUS MALIGNANT-MELANOMA; SELECTIVE BRAF INHIBITION; METASTATIC UVEAL MELANOMA; PULSED DENDRITIC CELLS; DOSE IMATINIB MESYLATE; STAGE IV MELANOMA; T-CELLS; B-RAF AB This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments. Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis. This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other "omics") scale analyses of tumors. The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research. The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy. C1 [Shtivelman, Emma] Canc Commons, Palo Alto, CA 94301 USA. [Davies, Michael A.; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yang, James] NCI, NIH, Washington, DC USA. [Lotem, Michal] Hadassah Hebrew Univ Hosp, Jerusalem, Israel. [Oren, Moshe] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Flaherty, Keith T.; Fisher, David E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Shtivelman, E (reprint author), Canc Commons, Palo Alto, CA 94301 USA. EM emma@cancercommons.org FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 348 TC 50 Z9 51 U1 0 U2 21 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR PY 2014 VL 5 IS 7 BP 1701 EP 1752 PG 52 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6EZ UT WOS:000336965400002 PM 24743024 ER PT J AU Sabbatino, F Wang, YY Wang, XH Flaherty, KT Yu, L Pepin, D Scognamiglio, G Pepe, S Kirkwood, JM Cooper, ZA Frederick, DT Wargo, JA Ferrone, S Ferrone, CR AF Sabbatino, Francesco Wang, Yangyang Wang, Xinhui Flaherty, Keith T. Yu, Ling Pepin, David Scognamiglio, Giosue Pepe, Stefano Kirkwood, John M. Cooper, Zachary A. Frederick, Dennie T. Wargo, Jennifer A. Ferrone, Soldano Ferrone, Cristina R. TI PDGFR alpha up-regulation mediated by Sonic Hedgehog pathway activation leads to BRAF inhibitor resistance in melanoma cells with BRAF mutation SO ONCOTARGET LA English DT Article DE BRAF inhibitor resistance; PDGFR alpha up-regulation; PDGFR alpha inhibitors; melanoma; sonic hedgehog pathway; LDE225 ID GASTROINTESTINAL STROMAL TUMORS; TRANSFERRED T-CELLS; ACQUIRED-RESISTANCE; IN-VIVO; B-RAF; IMATINIB MESYLATE; TARGETING STAT3; V600E MUTATION; MEK; PROTEIN AB Control of BRAF(V600E) metastatic melanoma by BRAF inhibitor (BRAF-I) is limited by intrinsic and acquired resistance. Growth factor receptor up-regulation is among the mechanisms underlying BRAF-I resistance of melanoma cells. Here we demonstrate for the first time that PDGFR alpha up-regulation causes BRAF-I resistance. PDGFR alpha inhibition by PDGFR alpha-specific short hairpin (sh) RNA and by PDGFR alpha inhibitors restores and increases melanoma cells' sensitivity to BRAF-I in vitro and in vivo. This effect reflects the inhibition of ERK and AKT activation which is associated with BRAF-I resistance of melanoma cells. PDGFR alpha up-regulation is mediated by Sonic Hedgehog Homolog (Shh) pathway activation which is induced by BRAF-I treatment. Similarly to PDGFR alpha inhibition, Shh inhibition by LDE225 restores and increases melanoma cells' sensitivity to BRAF-I. These effects are mediated by PDGFR alpha down-regulation and by ERK and AKT inhibition. The clinical relevance of these data is indicated by the association of PDGFR alpha up-regulation in melanoma matched biopsies of BRAF-I +/- MEK inhibitor treated patients with shorter time to disease progression and less tumor regression. These findings suggest that monitoring patients for early PDGFR alpha up-regulation will facilitate the identification of those who may benefit from the treatment with BRAF-I in combination with clinically approved PDGFR alpha or Shh inhibitors. C1 [Sabbatino, Francesco; Wang, Yangyang; Wang, Xinhui; Pepin, David; Cooper, Zachary A.; Frederick, Dennie T.; Wargo, Jennifer A.; Ferrone, Soldano; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Sabbatino, Francesco; Wang, Yangyang; Wang, Xinhui; Flaherty, Keith T.; Pepin, David; Cooper, Zachary A.; Frederick, Dennie T.; Wargo, Jennifer A.; Ferrone, Soldano; Ferrone, Cristina R.] Harvard Univ, Sch Med, Boston, MA USA. [Sabbatino, Francesco; Pepe, Stefano] Univ Naples Federico II, Dept Clin & Mol Oncol & Endocrinol, Naples, Italy. [Yu, Ling; Scognamiglio, Giosue] Univ Pittsburgh, Dept Surg, Inst Canc, Pittsburgh, PA USA. [Kirkwood, John M.] Univ Pittsburgh, Dept Med, Inst Canc, Pittsburgh, PA USA. [Yu, Ling] Southwest Univ, Inst Clean Energy & Adv Mat, Chongqing, Peoples R China. [Scognamiglio, Giosue] Fdn G Pascale, Ist Nazl Tumori, Pathol Unit, Naples, Italy. [Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Ferrone, S (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM sferrone@partners.org RI Yu, Ling/J-4286-2016; Scognamiglio, Giosue/K-8247-2016; OI Scognamiglio, Giosue/0000-0003-4376-111X; Sabbatino, Francesco/0000-0001-6431-8278 FU PHS - National Cancer Institute [RO1CA138188, RO1CA110249, P50CA121973]; Fondazione Umberto Veronesi Post Doctoral Fellowship - Fondazione Umberto Veronesi; Susan Komen Post Doctoral Fellowship - Susan G. Komen for the Cure Foundation [KG111486] FX This work was supported by PHS grants RO1CA138188, RO1CA110249 and P50CA121973 awarded by the National Cancer Institute, by a Fondazione Umberto Veronesi Post Doctoral Fellowship awarded by the Fondazione Umberto Veronesi, and by Susan Komen Post Doctoral Fellowship KG111486 awarded by the Susan G. Komen for the Cure Foundation. NR 60 TC 16 Z9 16 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR PY 2014 VL 5 IS 7 BP 1926 EP 1941 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6EZ UT WOS:000336965400018 PM 24732172 ER PT J AU Mitsui, Y Yasumoto, H Nagami, T Hiraki, M Arichi, N Ishikawa, N Araki, A Maruyama, R Tanaka, Y Dahiya, R Shiina, H AF Mitsui, Yozo Yasumoto, Hiroaki Nagami, Taichi Hiraki, Miho Arichi, Naoko Ishikawa, Noriyoshi Araki, Asuka Maruyama, Riruke Tanaka, Yuichiro Dahiya, Rajvir Shiina, Hiroaki TI Extracellular activation of Wnt signaling through epigenetic dysregulation of Wnt inhibitory factor-1 (Wif-1) is associated with pathogenesis of adrenocortical tumor SO ONCOTARGET LA English DT Article DE adrenocortical tumor; Wif-1; epigenetics; Wnt signaling; cyclin D1 ID RENAL-CELL CARCINOMA; BETA-CATENIN MUTATIONS; C-MYC; BLADDER-CANCER; LUNG-CANCER; CYCLIN D1; PATHWAY; EXPRESSION; FREQUENT; GENE AB Wnt/beta-catenin signaling is considered to be an essential regulator of adrenocortical oncogenesis. Wnt inhibitory factor-1 (Wif-1), an extracellular regulator of Wnt signaling, is frequently down-regulated by hypermethylation of the promoter CpG. We investigated epigenetic regulation of Wif-1 and its association with adrenocortical (AC) tumor pathogenesis in light of Wnt activation. The AC tumors showed a high prevalence of Wif-1 promoter methylation and low prevalence of Wif-1 mRNA transcription as compared to the normal adrenal (NA) samples. Furthermore, a significant correlation was found between Wif-1 promoter methylation and mRNA transcription in the tumors. Either intracellular beta-catenin accumulation or beta-catenin mRNA transcription was significantly elevated in the AC tumors, which also showed an inverse correlation with Wif-1 mRNA transcription. Cyclin D1, a target gene of Wnt signaling, was also up-regulated in the AC tumors as compared with the NA samples. In addition, down-regulation of Wif-1was correlated with increased cyclin D1 at both mRNA and protein levels. However, despite the proposed activation of Wnt signaling in AC tumors, only 2 of 20 with intracellular beta-catenin accumulation showed beta-catenin mutations. Thus, genetic alterations of beta-catenin and epigenetics-related Wif-1 promoter hypermethylation may be important mechanisms underlying AC tumor formation through aberrant canonical Wnt/beta-catenin signaling activation. C1 [Mitsui, Yozo; Yasumoto, Hiroaki; Nagami, Taichi; Hiraki, Miho; Arichi, Naoko; Shiina, Hiroaki] Shimane Univ, Fac Med, Dept Urol, Izumo, Shimane 6938501, Japan. [Ishikawa, Noriyoshi; Araki, Asuka; Maruyama, Riruke] Shimane Univ, Fac Med, Pathol Organ Pathol Unit, Izumo, Shimane 6938501, Japan. [Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Tanaka, Yuichiro; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Mitsui, Y (reprint author), Shimane Univ, Fac Med, Dept Urol, 89-1 Enya Cho, Izumo, Shimane 6938501, Japan. EM mitsui@med.shimane-u.ac.jp NR 35 TC 5 Z9 6 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD APR PY 2014 VL 5 IS 8 BP 2198 EP 2207 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AI6FC UT WOS:000336965800017 PM 24755523 ER PT J AU Damico, FM Takahashi, BS Acquesta, FB AF Damico, Francisco Max Takahashi, Beatriz S. Acquesta, Felipe B. TI TRANSSCLERAL DELIVERY OF Nd:YLF LASER AT 1,047 nm CAUSES VASCULAR OCCLUSION IN EXPERIMENTAL PIGMENTED CHOROIDAL MELANOMA SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE melanoma; experimental; lasers; disease models; animal; eye neoplasms ID COLLABORATIVE OCULAR MELANOMA; HAMSTER GREENE MELANOMA; COMS RANDOMIZED-TRIAL; UVEAL MELANOMA; TRANSPUPILLARY THERMOTHERAPY; EXTRASCLERAL EXTENSION; MALIGNANT MELANOMAS; RABBIT MODEL; EYES; ESTABLISHMENT AB Purpose: The aims of this study were to determine the scleral attenuation of focused neodymium: yttrium-lanthanum-fluoride laser at 1,047 nm applied transsclerally and whether transscleral delivery can close the vascular supply at the base of experimental choroidal melanoma in rabbits. Methods: Fifty-two New Zealand albino rabbits were included. Scleral laser attenuation was measured across fresh sclera. B16F10 melanomas were established in the subchoroidal space of 49 rabbits. Twenty-one animals were killed immediately after transscleral treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were performed before treatment, immediately after, and weekly during the follow-up. Eyes were examined by light microscopy. Results: Sclera attenuated laser energy by 31% +/- 7%. Immediately after treatment, angiography showed diffuse hypofluorescence in 71% (15 of 21 rabbits). Light microscopy showed vascular occlusion extending at least two thirds of the tumor thickness from the base. Seven of the 14 tumors followed for 15 days +/- 8 days were eradicated. There was no correlation between tumor height and eradication. Conclusion: Rabbit sclera attenuated 31% +/- 7% of laser energy. A single transscleral treatment causes tumor vascular closure at the base and may serve as an adjuvant therapy to ensure destruction of deep and intrascleral tumor cells. C1 [Damico, Francisco Max] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. [Damico, Francisco Max; Takahashi, Beatriz S.; Acquesta, Felipe B.] Univ Sao Paulo, Dept Ophthalmol, Sch Med, BR-05403900 Sao Paulo, Brazil. RP Damico, FM (reprint author), Univ Sao Paulo, Dept Ophthalmol, Sch Med, Av Dr Eneas Carvalho de Aguiar 255-6, BR-05403900 Sao Paulo, Brazil. EM fmdamico@usp.br FU Massachusetts Lions Eye Research Fund FX Supported in part by Massachusetts Lions Eye Research Fund. NR 27 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD APR PY 2014 VL 34 IS 4 BP 792 EP 800 PG 9 WC Ophthalmology SC Ophthalmology GA AI6DO UT WOS:000336960500029 PM 23974998 ER PT J AU Drain, PK Rhatigan, JJ AF Drain, Paul K. Rhatigan, Joseph J. TI Global Health Training Should Be Structured, Standardized, and Universal SO ACADEMIC MEDICINE LA English DT Letter ID MEDICAL-EDUCATION C1 [Drain, Paul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Rhatigan, Joseph J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Global Hlth Equ, Boston, MA 02115 USA. RP Drain, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM pdrain@partners.org RI yan, liu/A-1822-2015; OI yan, liu/0000-0001-8517-1084; Drain, Paul/0000-0003-3300-3817 NR 4 TC 0 Z9 0 U1 1 U2 5 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 APR PY 2014 VL 89 IS 4 BP 530 EP 531 DI 10.1097/ACM.0000000000000181 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AD6ZO UT WOS:000333410400006 PM 24667469 ER PT J AU Vaduganathan, M Rassiwala, J Evert, J AF Vaduganathan, Muthiah Rassiwala, Jasmine Evert, Jessica TI Potential Benefits of Collaboration in Short-Term Global Health Learning Experiences Reply SO ACADEMIC MEDICINE LA English DT Letter C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rassiwala, Jasmine] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Evert, Jessica] Univ Calif San Francisco, Dept Family & Community Med, Child Family Hlth Int & Clin Fac, San Francisco, CA 94143 USA. RP Vaduganathan, M (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jevert@fcm.ucsf.edu RI yan, liu/A-1822-2015 OI yan, liu/0000-0001-8517-1084 NR 2 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2014 VL 89 IS 4 BP 530 EP 530 DI 10.1097/ACM.0000000000000197 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AD6ZO UT WOS:000333410400005 PM 24667468 ER PT J AU Silber, JH Romano, PS Itani, KMF Rosen, AK Small, D Lipner, RS Bosk, CL Wang, YL Halenar, MJ Korovaichuk, S Even-Shoshan, O Volpp, KG AF Silber, Jeffrey H. Romano, Patrick S. Itani, Kamal M. F. Rosen, Amy K. Small, Dylan Lipner, Rebecca S. Bosk, Charles L. Wang, Yanli Halenar, Michael J. Korovaichuk, Sophia Even-Shoshan, Orit Volpp, Kevin G. TI Assessing the Effects of the 2003 Resident Duty Hours Reform on Internal Medicine Board Scores SO ACADEMIC MEDICINE LA English DT Article ID IN-TRAINING-EXAMINATION; ABIM CERTIFYING EXAMINATION; WORK-HOURS; SLEEP-DEPRIVATION; MEDICARE BENEFICIARIES; TEACHING HOSPITALS; HOURS REGULATIONS; AMERICAN BOARD; PATIENT SAFETY; DOSE-RESPONSE AB Purpose To determine whether the 2003 Accreditation Council for Graduate Medical Education (ACGME) duty hours reform affected medical knowledge as reflected by written board scores for internal medicine (IM) residents. Method The authors conducted a retrospective cohort analysis of postgraduate year 1 (PGY-1) Internal Medicine residents who started training before and after the 2003 duty hour reform using a merged data set of American Board of Internal Medicine (ABIM) Board examination and the National Board of Medical Examiners (NMBE) United States Medical Licensing Examination (USMLE) Step 2 Clinical Knowledge test scores. Specifically, using four regression models, the authors compared IM residents beginning PGY-1 training in 2000 and completing training unexposed to the 2003 duty hours reform (PGY-1 2000 cohort, n = 5,475) to PGY-1 cohorts starting in 2001 through 2005 (n = 28,008), all with some exposure to the reform. Results The mean ABIM board score for the unexposed PGY-1 2000 cohort (n = 5,475) was 491, SD = 85. Adjusting for demographics, program, and USMLE Step 2 exam score, the mean differences (95% CI) in ABIM board scores between the PGY-1 2001, 2002, 2003, 2004 and 2005 cohorts minus the PGY-1 2000 cohort were -5.43 (-7.63, -3.23), -3.44 (-5.65, -1.24), 2.58 (0.36, 4.79), 11.10 (8.88, 13.33) and 11.28 (8.98, 13.58) points respectively. None of these differences exceeded one-fifth of an SD in ABIM board scores. Conclusions The duty hours reforms of 2003 did not meaningfully affect medical knowledge as measured by scores on the ABIM board examinations. C1 [Silber, Jeffrey H.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Even-Shoshan, Orit] Univ Penn, Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Bosk, Charles L.; Even-Shoshan, Orit; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Romano, Patrick S.] Univ Calif Davis, Sch Med, Div Gen Med, Primary Care Outcomes Res Fac Dev Program, Sacramento, CA 95817 USA. [Romano, Patrick S.] Univ Calif Davis, Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA. [Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Itani, Kamal M. F.] VA Boston Hlth Care Syst, Boston, MA USA. [Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA. [Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Small, Dylan] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Lipner, Rebecca S.] Amer Board Internal Med, Philadelphia, PA USA. [Bosk, Charles L.] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. [Bosk, Charles L.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Wang, Yanli; Korovaichuk, Sophia; Even-Shoshan, Orit] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Halenar, Michael J.; Volpp, Kevin G.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Silber, JH (reprint author), Childrens Hosp Philadelphia, Ctr Outcomes Res, 3535 Market St,Suite 1029, Philadelphia, PA 19104 USA. EM silberj@wharton.upenn.edu RI Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 FU National Heart, Lung, and Blood Institute [R01 HL082637] FX This research was supported by a grant from the National Heart, Lung, and Blood Institute, Grant # R01 HL082637. NR 58 TC 4 Z9 4 U1 0 U2 3 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 APR PY 2014 VL 89 IS 4 BP 644 EP 651 DI 10.1097/ACM.0000000000000193 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AD6ZO UT WOS:000333410400032 PM 24556772 ER PT J AU Kesselheim, JC Sun, PL Woolf, AD London, WB Boyer, D AF Kesselheim, Jennifer C. Sun, Pengling Woolf, Alan D. London, Wendy B. Boyer, Debra TI Balancing Education and Service in Graduate Medical Education: Data From Pediatric Trainees and Program Directors SO ACADEMIC MEDICINE LA English DT Article ID COUNCIL AB Purpose To measure pediatric program directors' (PDs') and trainees' perceptions of and expectations for the balance of service and education in their training programs. Method In fall 2011, an electronic survey was sent to PDs and trainees at Boston Children's Hospital. Respondents described perceptions and expectations for service and education and rated the education and service inherent to 12 vignettes. Wilcoxon rank sum tests measured the agreement between PD and trainee perceptions and ratings of service and education assigned to each vignette. Results Responses were received from 28/39 PDs (78%) and 223/430 trainees (52%). Seventy-five (34%) trainees responded that their education had been compromised by excessive service obligations; only 1 (4%) PD agreed (P < .0001). Although 132 (59%) trainees reported that service obligations usually/sometimes predominated over clinical education, only 3 (11%) PDs agreed (P < .0001). One hundred trainees (45%) thought rotations never/rarely/sometimes provided a balance between education and clinical demands compared with 2 PDs (7%) (P < .0001). Both groups agreed that service can, without formal teaching, be considered educational. Trainees scored 6 vignettes as having greater educational value (P .01) and 10 as having lower service content (P .04) than PDs did. Conclusions Trainees and medical educators hold mismatched impressions of their training programs' balance of service and education. Trainees are more likely to report an overabundance of service. These data may impact the interpretation of Accreditation Council for Graduate Medical Education survey results and should be incorporated into dialogue about future curricular design initiatives. C1 [Kesselheim, Jennifer C.; Sun, Pengling; London, Wendy B.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA. [Woolf, Alan D.; Boyer, Debra] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA. RP Kesselheim, JC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_kesselheim@dfci.harvard.edu FU Academy for Teaching and Learning at Boston Children's Hospital FX The study was funded by the Academy for Teaching and Learning at Boston Children's Hospital. NR 8 TC 3 Z9 3 U1 0 U2 3 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 APR PY 2014 VL 89 IS 4 BP 652 EP 657 DI 10.1097/ACM.0000000000000174 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AD6ZO UT WOS:000333410400033 PM 24556769 ER PT J AU Mischoulon, D Price, LH Carpenter, LL Tyrka, AR Papakostas, GI Baer, L Dording, CM Clain, AJ Durham, K Walker, R Ludington, E Fava, M AF Mischoulon, David Price, Lawrence H. Carpenter, Linda L. Tyrka, Audrey R. Papakostas, George I. Baer, Lee Dording, Christina M. Clain, Alisabet J. Durham, Kelley Walker, Rosemary Ludington, Elizabeth Fava, Maurizio TI A Double-Blind, Randomized, Placebo-Controlled Clinical Trial of S-Adenosyl-l-Methionine (SAMe) Versus Escitalopram in Major Depressive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; RATING-SCALE; OUTPATIENTS; METAANALYSIS; OUTCOMES; RATES AB Objective: To examine the comparative antidepressant efficacy of S-adenosyl-l-methionine (SAMe) and escitalopram in a placebo-controlled, randomized, double-blind clinical trial. Method: One hundred eighty-nine outpatients (49.7% female, mean [SD] age = 45 [15] years) with DSM-IV-diagnosed major depressive disorder (MDD) were recruited from April 13, 2005, to December 22, 2009, at the Massachusetts General Hospital and at Butler Hospital. Patients were randomized for 12 weeks to SAMe 1,600-3,200 mg/d, escitalopram 10-20 mg/d, or placebo. Doses were escalated at 6 weeks in the event of nonresponse. The main outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS-17). Tolerability was assessed by the Systematic Assessment for Treatment of Emergent Events-Specific Inquiry (SAFTEE-SI). Results: All 3 treatment arms demonstrated a significant improvement of about 5-6 points in HDRS-17 scores (P < .001 for all), and no significant differences were observed between the treatment arms (P > .05 for all). Response rates in the intent-to-treat sample were 36% for SAMe, 34% for escitalopram, and 30% for placebo. Remission rates were 28% for SAMe, 28% for escitalopram, and 17% for placebo. No comparisons between treatment groups attained significance (P > .05 for all). Tolerability was good, with gastrointestinal side effects (19% for stomach discomfort and 20% for diarrhea) as the most common in the SAMe arm. Significant differences were observed between treatment groups for dizziness, anorgasmia, diminished mental acuity, and hot flashes (P < .05 for all). Conclusions: The results fail to support an advantage over placebo for either the investigational treatment SAMe or the standard treatment escitalopram for MDD. C1 [Mischoulon, David; Papakostas, George I.; Baer, Lee; Dording, Christina M.; Clain, Alisabet J.; Durham, Kelley; Walker, Rosemary; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Mischoulon, David; Papakostas, George I.; Baer, Lee; Dording, Christina M.; Clain, Alisabet J.; Durham, Kelley; Walker, Rosemary; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Price, Lawrence H.; Carpenter, Linda L.; Tyrka, Audrey R.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Mood Disorders Res Program,Butler Hosp, Providence, RI 02912 USA. [Price, Lawrence H.; Carpenter, Linda L.; Tyrka, Audrey R.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Lab Clin & Translat Neurosci,Butler Hosp, Providence, RI 02912 USA. [Ludington, Elizabeth] Agil Clin Inc, Carlsbad, CA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org RI Tyrka, Audrey/L-2504-2014 FU NIH; National Center for Complementary and Alternative Medicine (NCCAM), R01 grant [R01AT001638] FX This study was supported by the NIH and the National Center for Complementary and Alternative Medicine (NCCAM), R01 grant R01AT001638. SAMe tosylate and matching placebo were supplied by Pharmavite LLC, California. NR 29 TC 22 Z9 22 U1 2 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2014 VL 75 IS 4 BP 370 EP U133 DI 10.4088/JCP.13m08591 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AI0HA UT WOS:000336525700012 PM 24500245 ER PT J AU Perez-Rodriguez, MM Baca-Garcia, E Oquendo, MA Wang, S Wall, MM Liu, SM Blanco, C AF Mercedes Perez-Rodriguez, M. Baca-Garcia, Enrique Oquendo, Maria A. Wang, Shuai Wall, Melanie M. Liu, Shang-Min Blanco, Carlos TI Relationship Between Acculturation, Discrimination, and Suicidal Ideation and Attempts Among US Hispanics in the National Epidemiologic Survey of Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID UNITED-STATES 1991-1992; MENTAL-HEALTH; PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; LATINO ADOLESCENTS; COMORBIDITY SURVEY; MEXICAN-AMERICANS; MAJOR DEPRESSION; IMMIGRATION; RATES AB Objective: Acculturation is the process by which immigrants acquire the culture of the dominant society. Little is known about the relationship between acculturation and suicidal ideation and attempts among US Hispanics. Our aim was to examine the impact of 5 acculturation measures (age at migration, time in the United States, social network composition, language, race/ethnic orientation) on suicidal ideation and attempts in the largest available nationally representative sample of US Hispanics. Method: Study participants were US Hispanics (N = 6,359) from Wave 2 of the 2004-2005 National Epidemiologic Survey of Alcohol and Related Conditions (N = 34,653). We used linear chi(2) tests and logistic regression models to analyze the association between acculturation and risk of suicidal ideation and attempts. Results: Factors associated with a linear increase in lifetime risk for suicidal ideation and attempts were (1) younger age at migration (linear chi(2)(1) = 57.15; P < .0001), (2) longer time in the United States (linear chi(2)(1) = 36.09; P < .0001), (3) higher degree of English-language orientation (linear chi(2)(1) = 74.08; P < .0001), (4) lower Hispanic composition of social network (linear chi(2)(1) = 36.34; P < .0001), and (5) lower Hispanic racial/ethnic identification (linear chi(2)(1) = 47.77; P < .0001). Higher levels of perceived discrimination were associated with higher lifetime risk for suicidal ideation (beta = 0.051; P < .001) and attempts (beta = 0.020; P = .003). Conclusions: There was a linear association between multiple dimensions of acculturation and lifetime suicidal ideation and attempts. Discrimination was also associated with lifetime risk for suicidal ideation and attempts. Our results highlight protective aspects of the traditional Hispanic culture, such as high social support, coping strategies, and moral objections to suicide, which are modifiable factors and potential targets for public health interventions aimed at decreasing suicide risk. Culturally sensitive mental health resources need to be made more available to decrease discrimination and stigma. C1 [Mercedes Perez-Rodriguez, M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Mercedes Perez-Rodriguez, M.] James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY USA. [Mercedes Perez-Rodriguez, M.] James J Peters Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. [Mercedes Perez-Rodriguez, M.; Baca-Garcia, Enrique] CIBERSAM, Madrid, Spain. [Baca-Garcia, Enrique] Fdn Jimenez Diaz Hosp, Dept Psychiat, Madrid, Spain. [Baca-Garcia, Enrique] Univ Autonoma Madrid, Madrid, Spain. [Baca-Garcia, Enrique; Oquendo, Maria A.; Wang, Shuai; Liu, Shang-Min; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Baca-Garcia, Enrique; Oquendo, Maria A.; Wang, Shuai; Liu, Shang-Min; Blanco, Carlos] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Wall, Melanie M.] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA. RP Perez-Rodriguez, MM (reprint author), Mt Sinai Sch Med Psychiat, Box 1230,1 Gustave L Levy Pl, New York, NY 10029 USA. EM mercedes.perez@mssm.edu RI Perez Rodriguez, Maria/B-9410-2013; Baca-Garcia, Enrique/F-4106-2015 OI Perez Rodriguez, Maria/0000-0001-5137-1993; Baca-Garcia, Enrique/0000-0002-6963-6555 FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the Veterans Affairs; James J. Peters VAMC; Department of Veterans Affairs NY/NJ (VISN3) Mental Illness Research, Education, and Clinical Center; Alicia Koplowitz Foundation; Instituto de Salud Carlos III; CIBERSAM; Spanish Ministry of Health [SAF2010-21849]; NIH [DA019606, DA020783, DA023200, MH076051]; American Foundation for Suicide Prevention; New York State Psychiatric Institute; NIAAA FX This research is supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the Veterans Affairs, James J. Peters VAMC; the Department of Veterans Affairs NY/NJ (VISN3) Mental Illness Research, Education, and Clinical Center (Dr Perez-Rodriguez); the Alicia Koplowitz Foundation (Dr Baca-Garcia); Instituto de Salud Carlos III, CIBERSAM, and Spanish Ministry of Health grant SAF2010-21849 (Drs Baca-Garcia and Perez-Rodriguez); NIH grants DA019606, DA020783, DA023200, and MH076051 (Dr Blanco); American Foundation for Suicide Prevention (Dr Blanco); and New York State Psychiatric Institute (Drs Blanco and Oquendo). NESARC was funded by NIAAA with supplemental support from the National Institute on Drug Abuse. NR 45 TC 10 Z9 11 U1 3 U2 16 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2014 VL 75 IS 4 BP 399 EP 407 DI 10.4088/JCP.13m08548 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AI0HA UT WOS:000336525700017 PM 24813407 ER PT J AU Timpano, KR Rasmussen, JL Exner, C Rief, W Wilhelm, S AF Timpano, Kiara R. Rasmussen, Jessica L. Exner, Cornelia Rief, Winfried Wilhelm, Sabine TI The association between metacognitions, the obsessive compulsive symptom dimensions and hoarding: A focus on specificity SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Hoarding; Obsessive compulsive symptoms; Metacognitions ID PSYCHOMETRIC PROPERTIES; COGNITIVE ASPECTS; LATENT STRUCTURE; DISORDER; INVENTORY; MODEL; BELIEFS; ANXIETY; TRIAL; RESPONSIBILITY AB In recent year's metacognitive theories - particularly the self-regulatory executive function model proposed by Wells and colleagues - have emerged as a potentially useful perspective from which to extend current cognitive-behavioral models for the mood and anxiety disorders. Metacognitions refer to different beliefs individuals endorse about their thoughts, internal states, and effective coping strategies. Research has linked these attitudes to obsessive compulsive symptoms (OCS), yet it remains unclear whether there may be a differential association with the different OCS dimensions and hoarding. The current study aimed to investigate the specific relationships between the OCS dimensions, hoarding, and metacognitions controlling for general distress. The sample (N=160) was comprised of young adults at a large university in Germany. Although all symptom types were significantly linked with the various metacognitions assessed (all p's < .05), a series of linear regression analyses provided support for more nuanced and particular relationships. The analyses conducted allowed us to examine the specificity of any associations, by factoring out any shared variance between the different OCS dimensions and, hoarding. Results revealed that (1) positive beliefs about worry were significantly associated with obsessions and ordering; (2) negative beliefs about uncontrollability were significantly associated with obsessions and checking; (3) cognitive confidence was significantly associated with ordering and hoarding; (4) beliefs about the need to control thoughts were significantly associated with obsessions, ordering, and hoarding; and (5) cognitive self-consciousness was significantly linked with obsessions and ordering. Additional analyses were conducted to examine the relationships between metacognitions, hoarding-specific beliefs, and hoarding symptoms. Results are discussed from the perspective of current theoretical models of OCD and hoarding and future directions are also highlighted. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Timpano, Kiara R.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Rasmussen, Jessica L.; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Exner, Cornelia] Univ Leipzig, Dept Psychol, D-04109 Leipzig, Germany. [Rief, Winfried] Univ Marburg, Dept Psychol, D-35032 Marburg, Germany. RP Timpano, KR (reprint author), Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. EM kiaratimpano@gmail.com OI Exner, Cornelia/0000-0001-5904-6511 NR 59 TC 2 Z9 2 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD APR PY 2014 VL 3 IS 2 BP 188 EP 194 DI 10.1016/j.jocrd.2013.10.001 PG 7 WC Psychiatry SC Psychiatry GA AI0RZ UT WOS:000336558900016 ER PT J AU Jethwani, KS Mishra, SV Jethwani, PS Sawant, NS AF Jethwani, K. S. Mishra, S., V Jethwani, P. S. Sawant, N. S. TI Surveying Indian gay men for coping skills and HIV testing patterns using the internet SO JOURNAL OF POSTGRADUATE MEDICINE LA English DT Article DE COPE inventory; coping skills; HIV testing behavior; homosexual men; LGBT; online; web-based ID STRESS; HEALTH; RISK; SEX AB Background: Surveying vulnerable and incarcerated populations is often challenging. Newer methods to reach and collect sensitive information in a safe, secure, and valid manner can go a long way in addressing this unmet need. Homosexual men in India live with inadequate social support, marginalization, and lack legal recognition. These make them less reachable by public health agencies, and make them more likely to continue with high-risk behaviors, and contract human immunodeficiency virus (HIV). Aims: To understand coping skills and HIV testing patterns of homosexual men versus heterosexual men. Materials and Methods: An internet based study using a secure web platform and an anonymised questionnaire. The brief COPE Inventory was used to assess coping styles. Results: A total of 124 respondents were studied. Homosexual men used negative coping skills such as behavioral disengagement and tested for HIV significantly more often than heterosexual men. Heterosexual respondents used positive coping skills more often. The most commonly used coping skill by heterosexual men was instrumental coping and by homosexual men was acceptance. Discussion: Overall, homosexual men used negative coping mechanisms, like behavioral disengagement more often. The Indian family structure and social support is probably responsible for heterosexual men's over-reliance on instrumental coping, while resulting in disengagement in homosexuals. Conclusion: The lack of legal and social recognition of homosexuality has negatively impacted lives of gay men in India. This is strongly linked to harmful psychological and public health implications for HIV prevention and mental health for homosexual men. C1 [Jethwani, K. S.] Partners Hlth Care, Ctr Connected Hlth, Boston, MA 02114 USA. [Jethwani, K. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jethwani, K. S.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Mishra, S., V] Decimal Fdn, Mumbai, Maharashtra, India. [Jethwani, P. S.] Samhita Social Ventures, Dept NGO Relationships, Mumbai, Maharashtra, India. [Sawant, N. S.] King Edward Mem Hosp, Dept Psychiat, Mumbai, Maharashtra, India. RP Jethwani, KS (reprint author), Partners Hlth Care, Ctr Connected Hlth, Boston, MA 02114 USA. EM kamal83@gmail.com NR 17 TC 2 Z9 2 U1 0 U2 1 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0022-3859 J9 J POSTGRAD MED JI J. Postgrad. Med. PD APR-JUN PY 2014 VL 60 IS 2 BP 130 EP 134 DI 10.4103/0022-3859.132315 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AH9JX UT WOS:000336459500005 PM 24823510 ER PT J AU Hung, KJ Awtrey, CS Tsai, AC AF Hung, Kristin J. Awtrey, Christopher S. Tsai, Alexander C. TI Urinary Incontinence, Depression, and Economic Outcomes in a Cohort of Women Between the Ages of 54 and 65 Years SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID QUALITY-OF-LIFE; NURSING-HOME ADMISSION; UNITED-STATES; MENTAL-HEALTH; PREVALENCE; IMPACT; COSTS; DISABILITY; SYMPTOMS; SEEKING AB OBJECTIVE: To estimate the association between urinary incontinence (UI) and probable depression, work disability, and workforce exit. METHODS: The analytic sample consisted of 4,511 women enrolled in the population-based Health and Retirement Study cohort. The analysis baseline was 1996, the year that questions about UI were added to the survey instrument, and at which time study participants were 5465 years of age. Women were followed-up with biennial interviews until 2010-2011. Outcomes of interest were onset of probable depression, work disability, and workforce exit. Urinary incontinence was specified in different ways based on questions about experience and frequency of urine loss. We fit Cox proportional hazards regression models to the data, adjusting the estimates for baseline sociodemographic and health status variables previously found to confound the association between UI and the outcomes of interest. RESULTS: At baseline, 727 participants (survey-weighted prevalence, 16.6%; 95% confidence interval [ CI] 15.4-18.0) reported any UI, of which 212 (survey-weighted prevalence, 29.2%; 95% CI 25.4-33.3) reported urine loss on more than 15 days in the past month; and 1,052 participants were categorized as having probable depression (survey-weighted prevalence, 21.6%; 95% CI 19.8-23.6). Urinary incontinence was associated with increased risks for probable depression (adjusted hazard ratio, 1.43; 95% CI 1.27-1.62) and work disability (adjusted hazard ratio, 1.21; 95% CI 1.01-1.45), but not workforce exit (adjusted hazard ratio, 1.06; 95% CI 0.93-1.21). CONCLUSION: In a population-based cohort of women between ages 54 and 65 years, UI was associated with increased risks for probable depression and work disability. Improved diagnosis and management of UI may yield significant economic and psychosocial benefits. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Div Global Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Hung, KJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, 330 Brookline Ave,East Campus,Kirstein 317, Boston, MA 02215 USA. EM khung@bidmc.harvard.edu OI Tsai, Alexander/0000-0001-6397-7917 FU NIH [K23MH096620]; Robert Wood Johnson Foundation Health and Society Scholars Program FX Financial Disclosure Dr. Tsai receives salary support from NIH K23MH096620 and the Robert Wood Johnson Foundation Health and Society Scholars Program. The other authors did not report any potential conflicts of interest. NR 45 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2014 VL 123 IS 4 BP 822 EP 827 DI 10.1097/AOG.0000000000000186 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4BC UT WOS:000336809300015 PM 24785611 ER PT J AU Donahue, JJ McClure, KS Moon, SM AF Donahue, John J. McClure, Kelly S. Moon, Simon M. TI The Relationship Between Emotion Regulation Difficulties and Psychopathic Personality Characteristics SO PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT LA English DT Article DE psychopathy; emotion regulation; self-centered impulsivity; fearless dominance ID CONSTRUCT-VALIDITY; SELF-REPORT; INVENTORY; MODEL; DYSREGULATION; VALIDATION; DISORDER; BEHAVIOR; SUICIDE; RISK AB The factors of psychopathy assessment tools diverge in their relationships with numerous problematic behaviors and psychological disorders. Emotion dysregulation is a pathological process argued to cut across diagnoses, and may be important in better understanding these divergent associations. This study sought to clarify psychopathy's association with emotion regulation difficulties. It was predicted that the Fearless Dominance and Self-Centered Impulsivity factors of the Psychopathic Personality Inventory-Revised would demonstrate differential relationships with a multidimensional conceptualization of emotion regulation difficulties. Ninety-one male undergraduate students and 28 male court-mandated anger management participants completed self-report questionnaires measuring emotion regulation difficulties and psychopathic personality characteristics. Hierarchical regression analyses indicated that emotion regulation difficulties were negatively associated with Fearless Dominance psychopathic traits, but positively associated with Self-Centered Impulsivity and global psychopathic traits. In addition, emotion regulation difficulties explained incremental variance in psychopathic traits over and above negative affect alone. These findings may have clinical implications for the etiology and treatment of psychopathic personality disorder. C1 [Donahue, John J.] Portland VA Med Ctr, VISN Northwest Mental Illness Res Educ & Clin Ctr, Portland, OR 97239 USA. [McClure, Kelly S.; Moon, Simon M.] La Salle Univ, Dept Psychol, Philadelphia, PA 19141 USA. RP Donahue, JJ (reprint author), Portland VA Med Ctr, VISN Northwest Mental Illness Res Educ & Clin Ctr, P3MIRECC,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM John.Donahue4@va.gov NR 47 TC 5 Z9 5 U1 4 U2 19 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1949-2715 EI 1949-2723 J9 PERSONAL DISORD JI Personal. Disord. PD APR PY 2014 VL 5 IS 2 BP 186 EP 194 DI 10.1037/per0000025 PG 9 WC Psychology, Clinical SC Psychology GA AI3ES UT WOS:000336743400009 PM 24341861 ER PT J AU Yeo, RA Martinez, D Pommy, J Ehrlich, S Schulz, SC Ho, BC Bustillo, JR Calhoun, VD AF Yeo, R. A. Martinez, D. Pommy, J. Ehrlich, S. Schulz, S. C. Ho, B-C Bustillo, J. R. Calhoun, V. D. TI The impact of parent socio-economic status on executive functioning and cortical morphology in individuals with schizophrenia and healthy controls SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Executive function; frontal lobes; schizophrenia; socio-economic status; voxel-based morphometry ID 1ST-EPISODE SCHIZOPHRENIA; DEVELOPMENTAL INSTABILITY; BRAIN; CORTEX; MORPHOMETRY; ORIGIN AB Background. Relatively lower executive functioning is characteristic of individuals with schizophrenia. As low socioeconomic status (SES) early in life (i.e. parent SES) has been linked with lower executive skills in healthy children, we hypothesized that parental SES (pSES) would be more strongly related to executive functioning in individuals with schizophrenia than in controls and have a greater impact on prefrontal cortical morphology. Method. Healthy controls (n=125) and individuals with schizophrenia (n=102) completed tests assessing executive functioning and intelligence. The groups were matched on pSES, which was evaluated with the Hollingshead-Redlich scale. A principal components analysis (PCA) was conducted on 10 variables from six executive tests, yielding three specific components (fluency, planning and response inhibition). Voxel-based morphometry (VBM) was used to evaluate effects of pSES on gray matter (GM) concentration. Results. Lower pSES was associated with lower scores across the three executive functioning components, and a significant group by pSES interaction was observed such that low pSES, in particular, affected individuals with schizophrenia. These effects remained significant when intellectual ability, education and self-SES (sSES) were added as covariates. VBM revealed that lower pSES was associated with reduced GM volume in several anterior brain regions, especially the superior frontal gyrus, in patients but not in controls. Conclusions. These findings suggest that individuals with schizophrenia may be particularly vulnerable to the adverse impact of low pSES, in terms of both lower executive skills and reduced anterior GM volumes. C1 [Yeo, R. A.; Martinez, D.; Pommy, J.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Yeo, R. A.; Bustillo, J. R.; Calhoun, V. D.] Mind Res Network, Albuquerque, NM USA. [Ehrlich, S.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ehrlich, S.] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. [Schulz, S. C.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Ho, B-C] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Bustillo, J. R.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Calhoun, V. D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Yeo, RA (reprint author), Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. EM ryeo@unm.edu RI Ho, Beng-Choon/D-6959-2011; OI Ho, Beng-Choon/0000-0003-3976-1555; Ehrlich, Stefan/0000-0003-2132-4445 FU Department of Energy [DE-FG02-08ER64581]; National Institutes of Health [5P20RR021938, 1RC1MH089257, R01EB005846] FX This research was supported by grants from the Department of Energy under Award Number DE-FG02-08ER64581 and the National Institutes of Health (nos 5P20RR021938, 1RC1MH089257 and R01EB005846). NR 45 TC 5 Z9 6 U1 2 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2014 VL 44 IS 6 BP 1257 EP 1265 DI 10.1017/S0033291713001608 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AI2DX UT WOS:000336668700013 PM 23866983 ER PT J AU Gazourian, L Rogers, AJ Ibanga, R Weinhouse, GL Pinto-Plata, V Ritz, J Soiffer, RJ Antin, JH Washko, GR Baron, RM Ho, VT AF Gazourian, Lee Rogers, Angela J. Ibanga, Ruby Weinhouse, Gerald L. Pinto-Plata, Victor Ritz, Jerome Soiffer, Robert J. Antin, Joseph H. Washko, George R. Baron, Rebecca M. Ho, Vincent T. TI Factors associated with bronchiolitis obliterans syndrome and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; AIR-FLOW OBSTRUCTION; PULMONARY COMPLICATIONS; RANDOMIZED-TRIAL; RISK-FACTORS; ANTITHYMOCYTE GLOBULIN; LUNG TRANSPLANTATION; FOLLOW-UP; RECIPIENTS; MORTALITY AB Bronchiolitis obliterans syndrome (BOS) is a form of chronic graft vs. host disease (cGVHD) and a highly morbid pulmonary complication after allogeneic hematopoietic stem cell transplantation (HSCT). We assessed the prevalence and risk factors for BOS and cGVHD in a cohort of HSCT recipients, including those who received reduced intensity conditioning (RIC) HSCT. Between January 1, 2000 and June 30, 2010, all patients who underwent allogeneic HSCT at our institution (n=1854) were retrospectively screened for the development of BOS by PFT criteria. We matched the BOS cases with two groups of control patients: (1) patients who had concurrent cGVHD without BOS and (2) those who developed neither cGVHD nor BOS. Comparisons between BOS patients and controls were conducted using t-test or Fisher's exact tests. Multivariate regression analysis was performed to examine factors associated with BOS diagnosis. All statistical analyses were performed using SAS 9.2. We identified 89 patients (4.8%) meeting diagnostic criteria for BOS at a median time of 491 days (range: 48-2067) after HSCT. Eighty-six (97%) of our BOS cohort had extra-pulmonary cGVHD. In multivariate analysis compared to patients without cGVHD, patients who received busulfan-based conditioning, had unrelated donors, and had female donors were significantly more likely to develop BOS, while ATG administration was associated with a lower risk of BOS. Our novel results suggest that busulfan conditioning, even in RIC transplantation, could be an important risk factor for BOS and cGVHD. Am. J. Hematol. 89:404-409, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Gazourian, Lee; Ibanga, Ruby; Weinhouse, Gerald L.; Pinto-Plata, Victor; Washko, George R.; Baron, Rebecca M.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA. [Rogers, Angela J.] Stanford Univ, Dept Med, Div Pulm & Crit Care Med, Med Ctr, Stanford, CA 94305 USA. [Ritz, Jerome; Soiffer, Robert J.; Antin, Joseph H.; Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Dept Med Oncol, Boston, MA 02115 USA. RP Gazourian, L (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM lgazourian@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health [5T32HL007118-35, 5T32HL007680-20, 5T32HL007633-27, K23HL089353-05, HL107246-03, HL116473-01, HL091957]; Ted and Eileen Pasquarello Research Fund; NIH [CA142106, PO1HL070149-02]; Jock and Bunny Adams Education and Research Fund; Parker B. Francis Foundation FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: 5T32HL007118-35, 5T32HL007680-20, and 5T32HL007633-27 (Dr. Gazourian), K23HL089353-05, HL107246-03 and HL116473-01 (Dr. Washko), and HL091957 (Dr. Baron);; Contract grant sponsor: Ted and Eileen Pasquarello Research Fund (The DFCI BMT data repository);; Contract grant sponsor: NIH; Contract grant number: CA142106 and PO1HL070149-02 (The DFCI BMT data repository);; Contract grant sponsor: the Jock and Bunny Adams Education and Research Fund (The DFCI BMT data repository). Contract grant sponsor: Parker B. Francis Foundation (Dr. Rogers). NR 37 TC 9 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2014 VL 89 IS 4 BP 404 EP 409 DI 10.1002/ajh.23656 PG 6 WC Hematology SC Hematology GA AF3XL UT WOS:000334645900011 PM 24375545 ER PT J AU Freedman, AS AF Freedman, Arnold S. TI Follicular lymphoma: 2014 update on diagnosis and management SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; TERM-FOLLOW-UP; INTERNATIONAL PROGNOSTIC INDEX; BENDAMUSTINE PLUS RITUXIMAB; LOW-TUMOR-BURDEN; INDOLENT B-CELL; PHASE-II TRIAL; ANTI-CD20 MONOCLONAL-ANTIBODY AB Disease overview Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma (FL) is characterized by diffuse lymphoadenopathy, bone marrow involvement, splenomegaly, and less commonly other extranodal sites of involvement. In general cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. Diagnosis Diagnosis is based on histology of preferably a biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10, and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes. Risk stratification The Follicular Lymphoma International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age >60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas > 4. The presence of 0, 1, 2, and >= 3 adverse factors defines low, intermediate, and high-risk disease. With the use of more modern therapies, outcomes have improved. Risk-adapted therapy Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy-rituximab and single agent rituximab. Experimental therapies as well as stem cell transplantation (SCT) are considered for recurrent disease. Am. J. Hematol. 89:430-436, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Freedman, Arnold S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM afreedman@partners.org NR 113 TC 24 Z9 26 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2014 VL 89 IS 4 BP 429 EP 436 DI 10.1002/ajh.23674 PG 8 WC Hematology SC Hematology GA AF3XL UT WOS:000334645900015 PM 24687887 ER PT J AU Lemay, AC Anzueto, A Restrepo, MI Mortensen, EM AF Lemay, Allyson C. Anzueto, Antonio Restrepo, Marcos I. Mortensen, Eric M. TI Predictors of Long-term Mortality After Severe Sepsis in the Elderly SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Sepsis; Predictors; Mortality; Comorbid conditions ID COMORBIDITY INDEX; VETERANS-AFFAIRS; UNITED-STATES; EPIDEMIOLOGY; CARE; VALIDATION; TRAUMA; LIFE AB Background: Mortality rates after severe sepsis are extremely high, and the main focus of most research is short-term mortality, which may not be associated with long-term outcomes. The purpose of this study was to examine long-term mortality after a severe sepsis and identify factors associated with this mortality. Methods: The authors performed a population-based study using Veterans' Affairs administrative data of patients aged 65 years and older. The outcome of interest was mortality > 90 days following hospitalization. Our primary analyses were Cox proportional hazard models to examine specific risk factors for long-term mortality. Results: There were 2,727 patients that met the inclusion criteria. Overall mortality was 55%, and 1- and 2-year mortality rates were 31% and 43%, respectively. Factors significantly associated with long-term mortality included congestive heart failure, peripheral vascular disease, dementia, diabetes with complications and use of mechanical ventilation. Smoking cessation and cardiac medications were associated with decreased long-term mortality rates. Conclusions: The authors identified several factors, including receipt of mechanical ventilation, which were significantly associated with increased long-term mortality for survivors of severe sepsis. This information will help clinicians discuss prognosis with patients and their families. C1 [Restrepo, Marcos I.; Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT Res Program, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Lemay, Allyson C.; Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Div Hosp Med, Dept Med, San Antonio, TX 78229 USA. [Anzueto, Antonio; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, Dept Med, San Antonio, TX 78229 USA. RP Mortensen, EM (reprint author), Dallas VA Med Ctr, 4500 South Lancaster, Dallas, TX 75216 USA. EM Eric.Mortensen@UTSouthwestern.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research [R01NR010828] FX This study was supported by the National Institute of Nursing Research Grant R01NR010828. NR 24 TC 7 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD APR PY 2014 VL 347 IS 4 BP 282 EP 288 DI 10.1097/MAJ.0b013e318295a147 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AH0DG UT WOS:000335788700006 PM 23689053 ER PT J AU Mhyre, JM Tsen, LC Einav, S Kuklina, EV Leffert, LR Bateman, BT AF Mhyre, Jill M. Tsen, Lawrence C. Einav, Sharon Kuklina, Elena V. Leffert, Lisa R. Bateman, Brian T. TI Cardiac Arrest during Hospitalization for Delivery in the United States, 1998-2011 SO ANESTHESIOLOGY LA English DT Article ID CHRONIC HEART-DISEASE; MATERNAL MORBIDITY; CARDIOPULMONARY-RESUSCITATION; PREGNANCY; MORTALITY; SURVIVAL; WOMEN; RISK AB Background: The objective of this analysis was to evaluate the frequency, distribution of potential etiologies, and survival rates of maternal cardiopulmonary arrest during the hospitalization for delivery in the United States. Methods: By using data from the Nationwide Inpatient Sample during the years 1998 through 2011, the authors obtained weighted estimates of the number of U.S. hospitalizations for delivery complicated by maternal cardiac arrest. Clinical and demographic risk factors, potential etiologies, and outcomes were identified and compared in women with and without cardiac arrest. The authors tested for temporal trends in the occurrence and survival associated with maternal arrest. Results: Cardiac arrest complicated 1 in 12,000 or 8.5 per 100,000 hospitalizations for delivery (99% CI, 7.7 to 9.3 per 100,000). The most common potential etiologies of arrest included hemorrhage, heart failure, amniotic fluid embolism, and sepsis. Among patients with cardiac arrest, 58.9% of patients (99% CI, 54.8 to 63.0%) survived to hospital discharge. Conclusions: Approximately 1 in 12,000 hospitalizations for delivery is complicated by cardiac arrest, most frequently due to hemorrhage, heart failure, amniotic fluid embolism, or sepsis. Survival depends on the underlying etiology of arrest. C1 [Mhyre, Jill M.] Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI USA. [Tsen, Lawrence C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Einav, Sharon] Shaare Zedek Med Ctr, Intens Care Unit, Jerusalem, Israel. [Einav, Sharon] Hebrew Univ Jerusalem, Sch Med, IL-91010 Jerusalem, Israel. [Kuklina, Elena V.] US Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Atlanta, GA USA. [Leffert, Lisa R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med,Med Sch, Boston, MA 02115 USA. RP Mhyre, JM (reprint author), Univ Arkansas Med Sci, Dept Anesthesiol, 4301 West Markham St,Slot 515, Little Rock, AR 72205 USA. EM jmmhyre@uams.edu OI Tsen, Lawrence/0000-0002-1964-723X FU Intramural CDC HHS [CC999999] NR 32 TC 33 Z9 36 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2014 VL 120 IS 4 BP 810 EP 818 DI 10.1097/ALN.0000000000000159 PG 9 WC Anesthesiology SC Anesthesiology GA AG4HT UT WOS:000335381000009 PM 24694844 ER PT J AU Kida, K Shirozu, K Yu, BL Mandeville, JB Bloch, KD Ichinose, F AF Kida, Kotaro Shirozu, Kazuhiro Yu, Binglan Mandeville, Joseph B. Bloch, Kenneth D. Ichinose, Fumito TI Beneficial Effects of Nitric Oxide on Outcomes after Cardiac Arrest and Cardiopulmonary Resuscitation in Hypothermia-treated Mice SO ANESTHESIOLOGY LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; AMERICAN-HEART-ASSOCIATION; DECREASES INFARCTION SIZE; MYOCARDIAL-ISCHEMIA; STROKE MODEL; BRAIN-DAMAGE; INHALED NO; SYNTHASE; INHALATION; CARE AB Background: Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Although nitric oxide prevents organ injury induced by ischemia and reperfusion, role of nitric oxide during TH after CPR remains unclear. In this article, the authors examined the impact of endogenous nitric oxide synthesis on the beneficial effects of hypothermia after CA/CPR. The authors also examined whether or not inhaled nitric oxide during hypothermia further improves outcomes after CA/CPR in mice treated with TH. Methods: Wild-type mice and mice deficient for nitric oxide synthase 3 (NOS3(-/-)) were subjected to CA at 37 degrees C and then resuscitated with chest compression. Body temperature was maintained at 37 degrees C (normothermia) or reduced to 33 degrees C (TH) for 24 h after resuscitation. Mice breathed air or air mixed with nitric oxide at 10, 20, 40, 60, or 80 ppm during hypothermia. To evaluate brain injury and cerebral blood flow, magnetic resonance imaging was performed in wild-type mice after CA/CPR. Results: Hypothermia up-regulated the NOS3-dependent signaling in the brain (n = 6 to 7). Deficiency of NOS3 abolished the beneficial effects of hypothermia after CA/CPR (n = 5 to 6). Breathing nitric oxide at 40 ppm improved survival rate in hypothermia-treated NOS3(-/-) mice (n = 6) after CA/CPR compared with NOS3(-/-) mice that were treated with hypothermia alone (n = 6; P < 0.05). Breathing nitric oxide at 40 (n = 9) or 60 (n = 9) ppm markedly improved survival rates in TH-treated wild-type mice (n = 51) (both P < 0.05 vs. TH-treated wild-type mice). Inhaled nitric oxide during TH (n = 7) prevented brain injury compared with TH alone (n = 7) without affecting cerebral blood flow after CA/CPR (n = 6). Conclusions: NOS3 is required for the beneficial effects of TH. Inhaled nitric oxide during TH remains beneficial and further improves outcomes after CA/CPR. Nitric oxide breathing exerts protective effects after CA/CPR even when TH is ineffective due to impaired endogenous nitric oxide production. C1 [Kida, Kotaro; Shirozu, Kazuhiro; Yu, Binglan; Bloch, Kenneth D.; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Charlestown, MA 02129 USA. [Mandeville, Joseph B.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4315, Charlestown, MA 02129 USA. EM fichinose@partners.org FU American Heart Association's Founders Affiliate (Dallas, Texas); Massachusetts General Hospital Tosteson Fund for Medical Discovery (Boston, Massachusetts); R01 grants from the National Institutes of Health National Heart, Lung, and Blood Institute (Bethesda, Maryland) [HL101930, HL110378]; Foundation LeDucq (Paris, France) [10CVD02]; IKARIA Inc. (Hampton, New Jersey) FX This work was supported by postdoctoral fellowships from the American Heart Association's Founders Affiliate (Dallas, Texas) and from the Massachusetts General Hospital Tosteson Fund for Medical Discovery (Boston, Massachusetts) (to Dr. Kida), R01 grants from the National Institutes of Health National Heart, Lung, and Blood Institute (Bethesda, Maryland) (HL101930 to Dr. Ichinose and HL110378 to Drs. Ichinose and Bloch), a network grant (No. 10CVD02) from the Foundation LeDucq (Paris, France) (to Dr. Bloch), and a sponsored research agreement from IKARIA Inc. (Hampton, New Jersey) (to Dr. Ichinose). NR 26 TC 6 Z9 6 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2014 VL 120 IS 4 BP 880 EP 889 DI 10.1097/ALN.0000000000000149 PG 10 WC Anesthesiology SC Anesthesiology GA AG4HT UT WOS:000335381000016 PM 24496125 ER PT J AU Bengali, R Janik, LS Kurtz, M McGovern, F Jiang, YD AF Bengali, Raheel Janik, Luke S. Kurtz, Michael McGovern, Francis Jiang, Yandong TI Successful Cardiopulmonary Resuscitation in the Lateral Position during Intraoperative Cardiac Arrest SO ANESTHESIOLOGY LA English DT Article ID ABDOMINAL COMPRESSION CPR; OPEN-CHEST CPR; PRONE POSITION; VENTRICULAR-FIBRILLATION; PRECORDIAL THUMP C1 [Bengali, Raheel; Janik, Luke S.; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kurtz, Michael; McGovern, Francis] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Bengali, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM rbengali@partners.org NR 14 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2014 VL 120 IS 4 BP 1046 EP 1049 DI 10.1097/ALN.0b013e3182923eb9 PG 4 WC Anesthesiology SC Anesthesiology GA AG4HT UT WOS:000335381000034 PM 23558178 ER PT J AU Nichols, AJ Roussakis, E Klein, OJ Evans, CL AF Nichols, Alexander J. Roussakis, Emmanuel Klein, Oliver J. Evans, Conor L. TI Click-Assembled, Oxygen-Sensing Nanoconjugates for DepthResolved, Near-Infrared Imaging in a 3D Cancer Model SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer; click chemistry; dendrimers; imaging agents; nanotechnology ID PAMAM DENDRIMERS; PHOSPHORESCENCE; TISSUE AB Hypoxia is an important contributing factor to the development of drug-resistant cancer, yet few nonperturbative tools exist for studying oxygenation in tissues. While progress has been made in the development of chemical probes for optical oxygen mapping, penetration of such molecules into poorly perfused or avascular tumor regions remains problematic. A click-assembled oxygen-sensing (CAOS) nanoconjugate is reported and its properties demonstrated in an invitro 3D spheroid cancer model. The synthesis relies on the sequential click-based ligation of poly(amidoamine)-like subunits for rapid assembly. Near-infrared confocal phosphorescence microscopy was used to demonstrate the ability of the CAOS nanoconjugates to penetrate hundreds of micrometers into spheroids within hours and to show their sensitivity to oxygen changes throughout the nodule. This proof-of-concept study demonstrates a modular approach that is readily extensible to a wide variety of oxygen and cellular sensors for depth-resolved imaging in tissue and tissue models. C1 [Nichols, Alexander J.; Roussakis, Emmanuel; Klein, Oliver J.; Evans, Conor L.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Charlestown, MA 02129 USA. [Nichols, Alexander J.; Evans, Conor L.] Harvard Univ, Program Biophys, Boston, MA 02115 USA. [Nichols, Alexander J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Evans, CL (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, CNY 149-3210,13th St, Charlestown, MA 02129 USA. EM evans.conor@mgh.harvard.edu FU NSF; NDSEG; Air Force Office for Scientific Research [FA9550-13-1-0068]; National Institutes of Health through the NIH Director's New Innovator Award Program [1 DP2 OD007096-1] FX A.J.N. would like to acknowledge the support of an NSF Graduate Research Fellowship and an NDSEG Fellowship. This work was funded by the Air Force Office for Scientific Research (FA9550-13-1-0068) and the National Institutes of Health through the NIH Director's New Innovator Award Program, Grant No. 1 DP2 OD007096-1. Information on the New Innovator Award Program can be found at http://nihroadmap.nih.gov/newinnovator/. NR 13 TC 17 Z9 17 U1 2 U2 42 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD APR 1 PY 2014 VL 53 IS 14 BP 3671 EP 3674 DI 10.1002/anie.201311303 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA AD7MH UT WOS:000333447500009 PM 24590700 ER PT J AU Swanson, RA AF Swanson, Raymond A. TI Glucose, Acid, and Aspartate: Friends and Foes of the Axon SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ISCHEMIC-INJURY; NEURONAL DEATH; NADPH OXIDASE; WHITE-MATTER; HYPOGLYCEMIA C1 [Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA USA. RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. OI Swanson, Raymond/0000-0002-3664-5359 FU NINDS NIH HHS [R01 NS041421, R01 NS081149] NR 12 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2014 VL 75 IS 4 BP 490 EP 491 DI 10.1002/ana.24071 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG2GL UT WOS:000335234200004 PM 24272667 ER PT J AU Chen, YZ Friedman, JR Chen, DH Chan, GCK Bloss, CS Hisama, FM Topol, SE Carson, AR Pham, PH Bonkowski, ES Scott, ER Lee, JK Zhang, GF Oliveira, G Xu, J Scott-Van Zeeland, AA Chen, Q Levy, S Topol, EJ Storm, D Swanson, PD Bird, TD Schork, NJ Raskind, WH Torkamani, A AF Chen, Ying-Zhang Friedman, Jennifer R. Chen, Dong-Hui Chan, Guy C. -K. Bloss, Cinnamon S. Hisama, Fuki M. Topol, Sarah E. Carson, Andrew R. Pham, Phillip H. Bonkowski, Emily S. Scott, Erick R. Lee, Janel K. Zhang, Guangfa Oliveira, Glenn Xu, Jian Scott-Van Zeeland, Ashley A. Chen, Qi Levy, Samuel Topol, Eric J. Storm, Daniel Swanson, Phillip D. Bird, Thomas D. Schork, Nicholas J. Raskind, Wendy H. Torkamani, Ali TI Gain-of-Function ADCY5 Mutations in Familial Dyskinesia with Facial Myokymia SO ANNALS OF NEUROLOGY LA English DT Article ID ESSENTIAL BENIGN CHOREA; ADENYLYL-CYCLASE; GENETIC-VARIATION; FDFM; MAP AB ObjectiveTo identify the cause of childhood onset involuntary paroxysmal choreiform and dystonic movements in 2 unrelated sporadic cases and to investigate the functional effect of missense mutations in adenylyl cyclase 5 (ADCY5) in sporadic and inherited cases of autosomal dominant familial dyskinesia with facial myokymia (FDFM). MethodsWhole exome sequencing was performed on 2 parent-child trios. The effect of mutations in ADCY5 was studied by measurement of cyclic adenosine monophosphate (cAMP) accumulation under stimulatory and inhibitory conditions. ResultsThe same de novo mutation (c.1252C>T, p.R418W) in ADCY5 was found in both studied cases. An inherited missense mutation (c.2176G>A, p.A726T) in ADCY5 was previously reported in a family with FDFM. The significant phenotypic overlap with FDFM was recognized in both cases only after discovery of the molecular link. The inherited mutation in the FDFM family and the recurrent de novo mutation affect residues in different protein domains, the first cytoplasmic domain and the first membrane-spanning domain, respectively. Functional studies revealed a statistically significant increase in -receptor agonist-stimulated intracellular cAMP consistent with an increase in adenylyl cyclase activity for both mutants relative to wild-type protein, indicative of a gain-of-function effect. InterpretationFDFM is likely caused by gain-of-function mutations in different domains of ADCY5the first definitive link between adenylyl cyclase mutation and human disease. We have illustrated the power of hypothesis-free exome sequencing in establishing diagnoses in rare disorders with complex and variable phenotype. Mutations in ADCY5 should be considered in patients with undiagnosed complex movement disorders even in the absence of a family history. Ann Neurol 2014;75:542-549 C1 [Chen, Ying-Zhang; Hisama, Fuki M.; Raskind, Wendy H.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA. [Friedman, Jennifer R.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Friedman, Jennifer R.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Chen, Dong-Hui; Bonkowski, Emily S.; Swanson, Phillip D.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Chan, Guy C. -K.; Storm, Daniel] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Bloss, Cinnamon S.; Topol, Sarah E.; Carson, Andrew R.; Pham, Phillip H.; Scott, Erick R.; Lee, Janel K.; Zhang, Guangfa; Oliveira, Glenn; Scott-Van Zeeland, Ashley A.; Levy, Samuel; Topol, Eric J.; Schork, Nicholas J.; Torkamani, Ali] Scripps Hlth, Scripps Translat Sci Inst, San Diego, CA USA. [Bloss, Cinnamon S.; Topol, Sarah E.; Carson, Andrew R.; Pham, Phillip H.; Scott, Erick R.; Lee, Janel K.; Zhang, Guangfa; Oliveira, Glenn; Scott-Van Zeeland, Ashley A.; Levy, Samuel; Topol, Eric J.; Schork, Nicholas J.; Torkamani, Ali] Scripps Res Inst, San Diego, CA USA. [Xu, Jian] Northwestern Univ, Dept Physiol, Chicago, IL 60611 USA. [Chen, Qi] Fujian Normal Univ, Southern Biomed Res Ctr, Fuzhou, Peoples R China. [Bird, Thomas D.; Raskind, Wendy H.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Raskind, Wendy H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Raskind, Wendy H.] Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Torkamani, A (reprint author), 3344 North Torrey Pines Court,Ste 300, La Jolla, CA 92037 USA. EM atorkama@scripps.edu OI Topol, Eric/0000-0002-1478-4729 FU Scripps Genomic Medicine, an NIH National Center for Advancing Translational Sciences Clinical and Translational Science Award [5 UL1 RR025774]; Shaffer Family Foundation; Anne and Henry Zarrow Foundation; NIH/NHGRI [U01 HG006476]; NIH/NINDS [R01 NS069719, NS20498]; Department of Veterans Affairs; American Association for Cancer Research; Johnson Johnson FX This work is supported by Scripps Genomic Medicine, an NIH National Center for Advancing Translational Sciences Clinical and Translational Science Award (5 UL1 RR025774) to Scripps Translational Science Institute, as well as funding from the Shaffer Family Foundation and the Anne and Henry Zarrow Foundation. Further support is from NIH/NHGRI U01 HG006476 (A. T.), NIH/NINDS R01 NS069719 (W. H. R.), and NIH/NINDS NS20498 (D. S.), the Department of Veterans Affairs (T. D. B., W. H. R.), the American Association for Cancer Research (N.J.S.), and a research service contract with Johnson & Johnson (N.J.S.). NR 27 TC 24 Z9 25 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2014 VL 75 IS 4 BP 542 EP 549 DI 10.1002/ana.24119 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG2GL UT WOS:000335234200009 PM 24700542 ER PT J AU Serrano-Pozo, A Qian, J Monsell, SE Blacker, D Gomez-Isla, T Betensky, RA Growdon, JH Johnson, KA Frosch, MP Sperling, RA Hyman, BT AF Serrano-Pozo, Alberto Qian, Jing Monsell, Sarah E. Blacker, Deborah Gomez-Isla, Teresa Betensky, Rebecca A. Growdon, John H. Johnson, Keith A. Frosch, Matthew P. Sperling, Reisa A. Hyman, Bradley T. TI Mild to Moderate Alzheimer Dementia with Insufficient Neuropathological Changes SO ANNALS OF NEUROLOGY LA English DT Article ID NATIONAL INSTITUTE; DISEASE; PET; AUTOPSY AB Recently, approximate to 16% of participants in an anti-A passive immunotherapy trial for mild-to-moderate Alzheimer disease (AD) had a negative baseline amyloid positron emission tomography (PET) scan. Whether they have AD or are AD clinical phenocopies remains unknown. We examined the 2005-2013 National Alzheimer's Coordinating Center autopsy database and found that approximate to 14% of autopsied subjects clinically diagnosed with mild-to-moderate probable AD have no or sparse neuritic plaques, which would expectedly yield a negative amyloid PET scan. More than half of these A-negative subjects have low neurofibrillary tangle Braak stages. These findings support the implementation of a positive amyloid biomarker as an inclusion criterion in future anti-A drug trials. Ann Neurol 2014;75:597-601 C1 [Serrano-Pozo, Alberto; Blacker, Deborah; Gomez-Isla, Teresa; Betensky, Rebecca A.; Growdon, John H.; Johnson, Keith A.; Frosch, Matthew P.; Sperling, Reisa A.; Hyman, Bradley T.] Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA 02129 USA. [Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Johnson, Keith A.; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Qian, Jing] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Monsell, Sarah E.] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA. [Monsell, Sarah E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blacker, Deborah; Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Serrano-Pozo, Alberto] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. RP Hyman, BT (reprint author), Massachusetts Alzheimer Dis Res Ctr, 16th St,Bldg 114, Charlestown, MA 02129 USA. EM bhyman@mgh.harvard.edu OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU Massachusetts Alzheimer's Disease Research Center (NIH) [P50 AG0001534]; NIH National Institute on Aging [U01 AG016976] FX This work was supported by the Massachusetts Alzheimer's Disease Research Center (NIH grant P50 AG0001534; B. T. H.). The NACC database is funded by the NIH National Institute on Aging grant U01 AG016976, R.A.B. NR 20 TC 19 Z9 19 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2014 VL 75 IS 4 BP 597 EP 601 DI 10.1002/ana.24125 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG2GL UT WOS:000335234200015 PM 24585367 ER PT J AU Mannix, R Meehan, WP Feany, M Grant, PE Mandeville, J Kaplan, DL Whalen, M AF Mannix, Rebekah Meehan, William P. Feany, Mel Grant, Patricia Ellen Mandeville, Joseph Kaplan, David L. Whalen, Michael TI Genetic Influences and Neuropathological Sequelae of Repetitive Brain Injury Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Mannix, Rebekah] Childrens Hosp Boston, Div Emergency Med, Boston, MA 02115 USA. [Mannix, Rebekah; Meehan, William P.; Mandeville, Joseph; Whalen, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Meehan, William P.] Boston Childrens Hosp, Div Sports Med, Boston, MA USA. [Meehan, William P.] Micheli Ctr Sports Injury Prevent, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Grant, Patricia Ellen] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kaplan, David L.] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Whalen, Michael] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Mannix, R (reprint author), Childrens Hosp Boston, Div Emergency Med, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2014 VL 75 IS 4 BP 618 EP 618 DI 10.1002/ana.24056 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG2GL UT WOS:000335234200023 PM 24242978 ER PT J AU Alam, SN Yammine, H Moaven, O Ahmed, R Moss, AK Biswas, B Muhammad, N Biswas, R Raychowdhury, A Kaliannan, K Ghosh, S Ray, M Hamarneh, SR Barua, S Malo, NS Bhan, AK Malo, MS Hodin, RA AF Alam, Sayeda Nasrin Yammine, Halim Moaven, Omeed Ahmed, Rizwan Moss, Angela K. Biswas, Brishti Muhammad, Nur Biswas, Rakesh Raychowdhury, Atri Kaliannan, Kanakaraju Ghosh, Sathi Ray, Madhury Hamarneh, Sulaiman R. Barua, Soumik Malo, Nondita S. Bhan, Atul K. Malo, Madhu S. Hodin, Richard A. TI Intestinal Alkaline Phosphatase Prevents Antibiotic-Induced Susceptibility to Enteric Pathogens SO ANNALS OF SURGERY LA English DT Article DE antibiotic-associated diarrhea; bacterial pathogenesis; Clostridium difficile-associated disease; microbiotal homeostasis; salmonellosis ID DIFFICILE-ASSOCIATED DISEASE; GUT MICROBIOTA; INFECTION; DIARRHEA; INFLAMMATION; COLITIS; MICE; LIPOPOLYSACCHARIDE; TYPHIMURIUM; MODELS AB Objective: To determine the efficacy of oral supplementation of the gut enzyme intestinal alkaline phosphatase (IAP) in preventing antibiotic-associated infections from Salmonella enterica serovar Typhimurium (S. Typhimurium) and Clostridium difficile. Background: The intestinal microbiota plays a pivotal role in human health and well-being. Antibiotics inherently cause dysbiosis, an imbalance in the number and composition of intestinal commensal bacteria, which leads to susceptibility to opportunistic bacterial infections. Previously, we have shown that IAP preserves the normal homeostasis of intestinal microbiota and that oral supplementation with calf IAP (cIAP) rapidly restores the normal gut flora. We hypothesized that oral IAP supplementation would protect against antibiotic-associated bacterial infections. Methods: C57BL/6 mice were treated with antibiotic(s) cIAP in the drinking water, followed by oral gavage of S. Typhimurium or C. difficile. Mice were observed for clinical conditions and mortality. After a defined period of time, mice were killed and investigated for hematological, inflammatory, and histological changes. Results: We observed that oral supplementation with cIAP during antibiotic treatment protects mice from infections with S. Typhimurium as well as with C. difficile. Animals given IAP maintained their weight, had reduced clinical severity and gut inflammation, and showed improved survival. Conclusions: Oral IAP supplementation protected mice from antibiotic-associated bacterial infections. We postulate that oral IAP supplementation could represent a novel therapy to protect against antibiotic-associated diarrhea (AAD), C. difficile-associated disease (CDAD), and other enteric infections in humans. C1 [Alam, Sayeda Nasrin; Yammine, Halim; Moaven, Omeed; Ahmed, Rizwan; Moss, Angela K.; Biswas, Brishti; Muhammad, Nur; Biswas, Rakesh; Raychowdhury, Atri; Kaliannan, Kanakaraju; Ghosh, Sathi; Ray, Madhury; Hamarneh, Sulaiman R.; Barua, Soumik; Malo, Nondita S.; Malo, Madhu S.; Hodin, Richard A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Malo, MS (reprint author), Massachusetts Gen Hosp, Dept Surg, Jackson 812,55 Fruit Stt, Boston, MA 02114 USA. EM mmalo@partners.org RI kaliannan, kanakaraju/P-9094-2014; OI Moaven, Omeed/0000-0002-0560-0457 FU National Institute of Health [R01DK050623, R01DK047186]; Gates Foundation Grand Challenge Exploration Grant [OPP1008158]; National Institutes of Health [2P30 DK43351] FX Supported by the National Institute of Health grants R01DK050623 and R01DK047186 to RAH, the Gates Foundation Grand Challenge Exploration Grant OPP1008158 to MSM, and the National Institutes of Health grant 2P30 DK43351 to the Center for the Study of Inflammatory Bowel Disease, MGH. NR 41 TC 10 Z9 10 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD APR PY 2014 VL 259 IS 4 BP 715 EP 722 DI 10.1097/SLA.0b013e31828fae14 PG 8 WC Surgery SC Surgery GA AH6NK UT WOS:000336247400033 PM 23598380 ER PT J AU Lee, E Koo, Y Ng, A Wei, YJ Luby-Phelps, K Juraszek, A Xavier, RJ Cleaver, O Levine, B Amatruda, JF AF Lee, Eunmyong Koo, Yeon Ng, Aylwin Wei, Yongjie Luby-Phelps, Kate Juraszek, Amy Xavier, Ramnik J. Cleaver, Ondine Levine, Beth Amatruda, James F. TI Autophagy is essential for cardiac morphogenesis during vertebrate development SO AUTOPHAGY LA English DT Article DE autophagy; zebrafish; heart development; tbx2; atg5; atg7; becn1 ID C. ELEGANS; CELL-DEATH; EMBRYONIC-DEVELOPMENT; MAMMALIAN DEVELOPMENT; HEMODYNAMIC STRESS; ZEBRAFISH EMBRYOS; SELF-DIGESTION; APOPTOTIC CELL; GENES FUNCTION; HEART FIELD AB Genetic analyses indicate that autophagy, an evolutionarily conserved lysosomal degradation pathway, is essential for eukaryotic differentiation and development. However, little is known about whether autophagy contributes to morphogenesis during embryogenesis. To address this question, we examined the role of autophagy in the early development of zebrafish, a model organism for studying vertebrate tissue and organ morphogenesis. Using zebrafish that transgenically express the fluorescent autophagy reporter protein, GFP-LC3, we found that autophagy is active in multiple tissues, including the heart, during the embryonic period. Inhibition of autophagy by morpholino knockdown of essential autophagy genes (including atg5, atg7, and becn1) resulted in defects in morphogenesis, increased numbers of dead cells, abnormal heart structure, and reduced organismal survival. Further analyses of cardiac development in autophagy-deficient zebrafish revealed defects in cardiac looping, abnormal chamber morphology, aberrant valve development, and ectopic expression of critical transcription factors including foxn4, tbx5, and tbx2. Consistent with these results, Atg5-deficient mice displayed abnormal Tbx2 expression and defects in valve development and chamber septation. Thus, autophagy plays an essential, conserved role in cardiac morphogenesis during vertebrate development. C1 [Lee, Eunmyong; Wei, Yongjie; Levine, Beth; Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Koo, Yeon; Cleaver, Ondine; Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, Aylwin; Xavier, Ramnik J.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Wei, Yongjie; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA. [Wei, Yongjie; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Luby-Phelps, Kate] UT Southwestern Med Ctr, Dept Cell Biol, Dallas, TX USA. [Juraszek, Amy; Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. RP Amatruda, JF (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. EM beth.levine@utsouthwestern.edu; james.amatruda@utsouthwestern.edu OI Cleaver, Ondine/0000-0003-2454-6641 FU Amon G Carter Foundation; CPRIT [RP120718-P1]; [5R01CA135731]; [R01CA109618] FX We thank Ashley Ratley for zebrafish care. This work was supported by grant 5R01CA135731 and a grant from the Amon G Carter Foundation to JFA; and R01CA109618 and CPRIT RP120718-P1 to BL. We thank Daniel Klionsky, Noboru Mizushima, and Tom Look for providing critical reagents and Haley Harrington for providing assistance with manuscript preparation. NR 65 TC 25 Z9 25 U1 1 U2 18 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD APR 1 PY 2014 VL 10 IS 4 BP 572 EP 587 DI 10.4161/auto.27649 PG 16 WC Cell Biology SC Cell Biology GA AG6SD UT WOS:000335547800004 PM 24441423 ER PT J AU Dotto, GP Lefort, K AF Dotto, G. Paolo Lefort, Karine TI miR-34a/SIRT6 in squamous differentiation and cancer SO CELL CYCLE LA English DT Editorial Material DE miR-34a; squamous differentiation; p53; SIRT6; squamous cell carcinoma; actinic keratosis ID NETWORK; SIRT6 C1 [Dotto, G. Paolo; Lefort, Karine] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lefort, Karine] Univ Hosp CHUV, Dept Dermatol, Lausanne, Switzerland. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. EM paolo.dotto@unil.ch; karine.lefort@unil.ch FU NIAMS NIH HHS [R01 AR039190, AR39190] NR 8 TC 5 Z9 5 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 APR 1 PY 2014 VL 13 IS 7 BP 1055 EP 1056 DI 10.4161/cc.28378 PG 2 WC Cell Biology SC Cell Biology GA AG5JR UT WOS:000335455800004 PM 24583844 ER PT J AU Reddy, YM Chinitz, L Mansour, M Bunch, TJ Mahapatra, S Swarup, V Di Biase, L Bommana, S Atkins, D Tung, R Shivkumar, K Burkhardt, JD Ruskin, J Natale, A Lakkireddy, D AF Reddy, Yeruva Madhu Chinitz, Larry Mansour, Moussa Bunch, T. Jared Mahapatra, Srijoy Swarup, Vijay Di Biase, Luigi Bommana, Sudharani Atkins, Donita Tung, Roderick Shivkumar, Kalyanam Burkhardt, J. David Ruskin, Jeremy Natale, Andrea Lakkireddy, Dhanunjaya TI Percutaneous Left Ventricular Assist Devices in Ventricular Tachycardia Ablation Multicenter Experience SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; intra-aortic balloon pumping; tachycardia; ventricular ID CATHETER ABLATION; MYOCARDIAL-INFARCTION; ARRHYTHMIAS; SUPPORT AB Background Data on relative safety, efficacy, and role of different percutaneous left ventricular assist devices for hemodynamic support during the ventricular tachycardia (VT) ablation procedure are limited. Methods and Results We performed a multicenter, observational study from a prospective registry including all consecutive patients (N=66) undergoing VT ablation with a percutaneous left ventricular assist devices in 6 centers in the United States. Patients with intra-aortic balloon pump (IABP group; N=22) were compared with patients with either an Impella or a TandemHeart device (non-IABP group; N=44). There were no significant differences in the baseline characteristics between both the groups. In non-IABP group (1) more patients could undergo entrainment/activation mapping (82% versus 59%; P=0.046), (2) more number of unstable VTs could be mapped and ablated per patient (1.050.78 versus 0.32 +/- 0.48; P<0.001), (3) more number of VTs could be terminated by ablation (1.59 +/- 1.0 versus 0.91 +/- 0.81; P=0.007), and (4) fewer VTs were terminated with rescue shocks (1.9 +/- 2.2 versus 3.0 +/- 1.5; P=0.049) when compared with IABP group. Complications of the procedure trended to be more in the non-IABP group when compared with those in the IABP group (32% versus 14%; P=0.143). Intermediate term outcomes (mortality and VT recurrence) during 12 +/- 5-month follow-up were not different between both groups. Left ventricular ejection fraction 15% was a strong and independent predictor of in-hospital mortality (53% versus 4%; P<0.001). Conclusions Impella and TandemHeart use in VT ablation facilitates extensive activation mapping of several unstable VTs and requires fewer rescue shocks during the procedure when compared with using IABP. C1 [Reddy, Yeruva Madhu; Bommana, Sudharani; Atkins, Donita; Lakkireddy, Dhanunjaya] Univ Kansas Hosp, Cardiovasc Res Inst, Div Cardiovasc Dis, Kansas City, KS 66160 USA. [Reddy, Yeruva Madhu; Bommana, Sudharani; Atkins, Donita; Lakkireddy, Dhanunjaya] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Chinitz, Larry] NYU, Sch Med, Div Cardiol, New York, NY USA. [Mansour, Moussa; Ruskin, Jeremy] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bunch, T. Jared] Intermt Heart Inst, Salt Lake City, UT USA. [Mahapatra, Srijoy] St Jude Med, St Paul, MN USA. [Swarup, Vijay] Arizona Heart Rhythm Ctr, Phoenix, AZ USA. [Di Biase, Luigi; Burkhardt, J. David; Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Tung, Roderick; Shivkumar, Kalyanam] UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA. RP Lakkireddy, D (reprint author), Univ Kansas Hosp, Bloch Heart Rhythm Ctr, KU Cardiovasc Res Inst, 3901 Rainbow Blvd MS 4023, Kansas City, KS 66160 USA. EM dlakkireddy@gmail.com OI Shivkumar, Kalyanam/0000-0002-4121-1766; Di Biase, Luigi/0000-0001-6508-4047 FU NHLBI NIH HHS [R01 HL084261] NR 14 TC 23 Z9 23 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2014 VL 7 IS 2 BP 244 EP 250 DI 10.1161/CIRCEP.113.000548 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG1XO UT WOS:000335209700012 PM 24532564 ER PT J AU Magnani, JW Moser, CB Murabito, JM Sullivan, LM Wang, N Ellinor, PT Vasan, RS Benjamin, EJ Coviello, AD AF Magnani, Jared W. Moser, Carlee B. Murabito, Joanne M. Sullivan, Lisa M. Wang, Na Ellinor, Patrick T. Vasan, Ramachandran S. Benjamin, Emelia J. Coviello, Andrea D. TI Association of Sex Hormones, Aging, and Atrial Fibrillation in Men The Framingham Heart Study SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE aging; atrial fibrillation; epidemiology; men ID POPULATION-BASED COHORT; LOW TESTOSTERONE LEVELS; LOW SERUM TESTOSTERONE; ELDERLY-MEN; ATHEROSCLEROSIS RISK; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; MORTALITY; ESTRADIOL; FAILURE AB Background Endogenous sex hormones have been related to cardiovascular outcomes and mortality. We hypothesized that sex hormones are related to atrial fibrillation (AF) in a community-based cohort of middle-aged to older men. Methods and Results We examined testosterone, estradiol, and dehydroepiandrosterone sulfate in relation to incident AF in men participating in the Framingham Heart Study. We assessed the 10-year risk of AF in multivariable-adjusted hazard models. The cohort consisted of 1251 men (age, 68.08.2 years), of whom 275 developed incident AF. We identified a significant interaction between age and testosterone and, therefore, stratified men into age 55 to 69 years (n=786), 70 to 79 years (n=351), and 80 years (n=114). In men aged 55 to 69 years, each 1 SD decrease in testosterone was associated with hazard ratio (HR) 1.30 (95% confidence interval [CI], 1.07-1.59) for incident AF. The association between testosterone and 10-year incident AF in men 70 to 79 years did not reach statistical significance. In men 80 years, a 1 SD decrease in testosterone was associated with HR 3.53 (95% CI, 1.96-6.37) for AF risk. Estradiol was associated with incident AF (HR, 1.12; 95% CI, 1.01-1.26). Dehydroepiandrosterone sulfate had a borderline association with risk of AF that was not statistically significant (HR, 1.12; 95% CI, 0.99-1.28). Conclusions Testosterone and estradiol are associated with incident AF in a cohort of older men. Testosterone deficiency in men 80 years is strongly associated with AF risk. The clinical and electrophysiological mechanisms underlying the associations between sex hormones and AF in older men merit continued investigation. C1 [Magnani, Jared W.; Murabito, Joanne M.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Coviello, Andrea D.] NHLBI, Boston, MA USA. [Magnani, Jared W.; Murabito, Joanne M.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Coviello, Andrea D.] Boston Univ, Framingham Heart Study, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Coviello, Andrea D.] Boston Univ, Dept Med, Div Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Moser, Carlee B.; Sullivan, Lisa M.; Wang, Na] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.; Coviello, Andrea D.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF219028, 13EIA14220013]; National Institutes of Health [1R03AG045075, HL092577, RO1AG028321, RC1-HL01056, 1R01HL102214, R01 AG29451, 1RO1HL104156, 1K24HL105780, RO1HL094755, 6R01-NS17950, N01-HC25195]; Boston University School of Medicine Department of Medicine Career Investment Award FX This work was supported by an American Heart Association award to J.W.M. (09FTF219028) and P.T.E (13EIA14220013). This work was supported by grants from the National Institutes of Health 1R03AG045075 (to J.W.M.), HL092577 (to E.J.B. and P.T.E.), RO1AG028321, RC1-HL01056, 1R01HL102214 (to E.J.B.), R01 AG29451 (to J.M.M.), 1RO1HL104156, 1K24HL105780 (to P.T.E.), RO1HL094755 (to A.D.C.), 6R01-NS17950, and N01-HC25195, J.W.M. is further supported by a Boston University School of Medicine Department of Medicine Career Investment Award. The authors are solely responsible for the design and conduct of this study, the study analyses, and the drafting and editing of the article, and its final contents. NR 43 TC 12 Z9 12 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2014 VL 7 IS 2 BP 307 EP 312 DI 10.1161/CIRCEP.113.001322 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG1XO UT WOS:000335209700021 PM 24610804 ER PT J AU Harbin, JM Gelso, CJ Rojas, AEP AF Harbin, James M. Gelso, Charles J. Rojas, Andres E. Perez TI Therapist Work With Client Strengths: Development and Validation of a Measure SO COUNSELING PSYCHOLOGIST LA English DT Article DE positive psychotherapy; strengths; positive psychology; self-report measure ID COUNSELING PSYCHOLOGY RESEARCH; POSITIVE PSYCHOLOGY; SELF-CONSCIOUSNESS; PSYCHOTHERAPY; MODEL; PSYCHOPATHOLOGY; INTERVENTIONS; PERSPECTIVE; SUPPORT; SCALE AB Two studies were conducted to investigate the Inventory of Therapist Work With Client Assets and Strengths (IT-WAS), a new measure constructed to assess the importance therapists place on incorporating strength-based approaches in their therapeutic work. In the first study, a combined sample (N = 225), comprising therapists in independent practice, graduate students and faculty in counseling-related fields, and counseling center staff at a large mid-Atlantic university was gathered to conduct an exploratory factor analysis. Results yielded three factors (Theory of Intervention, Assessment of Strengths, and Supporting Progress). The data also provided evidence for the IT-WAS's internal consistency and validity, the latter being supported by correlations with measures of theoretically relevant constructs. In the second study, data from 31 counseling and clinical doctoral students provided evidence for the IT-WAS's test-retest reliability over a 2-week period. Implications for clinical training and practice are discussed, and areas of future research are provided. C1 [Harbin, James M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Harbin, James M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Gelso, Charles J.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Rojas, Andres E. Perez] Univ Maryland, Counseling Psychol Program, College Pk, MD 20742 USA. RP Gelso, CJ (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM gelso@umd.edu NR 52 TC 2 Z9 2 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0011-0000 EI 1552-3861 J9 COUNS PSYCHOL JI Couns. Psychol. PD APR PY 2014 VL 42 IS 3 BP 345 EP 373 DI 10.1177/0011000012470570 PG 29 WC Psychology, Applied SC Psychology GA AB7KU UT WOS:000331969700003 ER PT J AU Tapias, LF Ott, HC AF Tapias, Luis F. Ott, Harald C. TI Decellularized scaffolds as a platform for bioengineered organs SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE bioartificial organs; regeneration; stem cells; tissue scaffolds; transplantation ID LUNG DE-CELLULARIZATION; EXTRACELLULAR-MATRIX; STEM-CELLS; IN-VITRO; ORTHOTOPIC TRANSPLANTATION; REGENERATIVE MEDICINE; MECHANICAL-PROPERTIES; RE-CELLULARIZATION; PORCINE KIDNEYS; RAT-LIVER AB Purpose of reviewPatients suffering from end-stage organ failure requiring organ transplantation face donor organ shortage and adverse effect of chronic immunosuppression. Recent progress in the field of organ bioengineering based on decellularized organ scaffolds and patient-derived cells holds great promise to address these issues.Recent findingsPerfusion-decellularization is the most consistent method to obtain decellularized whole-organ scaffolds to serve as a platform for organ bioengineering. Important advances have occurred in organ bioengineering using decellularized scaffolds in small animal models. However, the function exhibited by bioengineered organs has been rudimentary. Pluripotent stem cells seem to hold promise as the ideal regenerative cells to be used with this approach but the techniques to effectively and reliably manipulate their fate are still to be discovered. Finally, this technology needs to be scaled up to human size to be of clinical relevance.SummaryThe search for alternatives to allogeneic organ transplantation continues. Important milestones have been achieved in organ bioengineering with the use of decellularized scaffolds. However, many challenges remain on the way to producing an autologous, fully functional organ that can be transplanted similar to a donor organ. C1 [Tapias, Luis F.; Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Tapias, Luis F.; Ott, Harald C.] Harvard Univ, Sch Med, Boston, MA USA. [Ott, Harald C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Ott, Harald C.] Harvard Stem Cell Inst, Boston, MA USA. RP Ott, HC (reprint author), 185 Cambridge St,CPZN 4800, Boston, MA 02114 USA. EM hott@mgh.harvard.edu FU NIH [DP2 OD008749-01] FX The present study was supported by the NIH Director's New Innovator Award DP2 OD008749-01, and departmental funds. NR 68 TC 23 Z9 26 U1 6 U2 57 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD APR PY 2014 VL 19 IS 2 BP 145 EP 152 DI 10.1097/MOT.0000000000000051 PG 8 WC Transplantation SC Transplantation GA AD5LF UT WOS:000333293600011 PM 24480969 ER PT J AU Yang, CH David, L Qiao, Q Damko, E Wu, H AF Yang, Chenghua David, Liron Qiao, Qi Damko, Ermelinda Wu, Hao TI The CBM signalosome: Potential therapeutic target for aggressive lymphoma? SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Article; Proceedings Paper CT 14th International TNF Conference - Recent Advances toward Future Challenges CY JUL 07-10, 2013 CL Quebec, CANADA DE CBM complex; Lymphoma; NF-kappa B; Targeted therapy ID NF-KAPPA-B; T-CELL-ACTIVATION; PROTEIN-PROTEIN INTERACTIONS; SMALL-MOLECULE INHIBITORS; MALT LYMPHOMA; PARACASPASE MALT1; RECEPTOR STIMULATION; SIGNALING PATHWAYS; CRYSTAL-STRUCTURE; UBIQUITIN LIGASE AB The CBM signalosome plays a pivotal role in mediating antigen-receptor induced NF-kappa B signaling to regulate lymphocyte functions. The CBM complex forms filamentous structure and recruits downstream signaling components to activate NF-KB. MALT1, the protease component in the CBM complex, cleaves key proteins in the feedback loop of the NF-KB signaling pathway and enhances NF-KB activation. The aberrant activity of the CBM complex has been linked to aggressive lymphoma. Recent years have witnessed dramatic progresses in understanding the assembly mechanism of the CBM complex, and advances in the development of targeted therapy for aggressive lymphoma. Here, we will highlight these progresses and give an outlook on the potential translation of this knowledge from bench to bedside for aggressive lymphoma patients. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Yang, Chenghua] Second Mil Med Univ, Changhai Hosp, Joint Ctr Translat Res Chron Dis, Shanghai 200433, Peoples R China. [Yang, Chenghua] Sloan Kettering Inst, Dept Mol Pharmacol & Chem, New York, NY 10021 USA. [David, Liron; Qiao, Qi; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [David, Liron; Qiao, Qi; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Damko, Ermelinda; Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA. RP Yang, CH (reprint author), Second Mil Med Univ, Changhai Hosp, Joint Ctr Translat Res Chron Dis, Shanghai 200433, Peoples R China. EM chyang@sibs.ac.cn FU NIAID NIH HHS [R01 AI089882, R01AI089882] NR 63 TC 3 Z9 4 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 EI 1879-0305 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD APR PY 2014 VL 25 IS 2 BP 175 EP 183 DI 10.1016/j.cytogfr.2013.12.008 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH4PV UT WOS:000336111400011 PM 24411492 ER PT J AU Florez, H Temprosa, MG Orchard, TJ Mather, KJ Marcovina, SM Barrett-Connor, E Horton, E Saudek, C Pi-Sunyer, XF Ratner, RE Goldberg, RB AF Florez, H. Temprosa, M. G. Orchard, T. J. Mather, K. J. Marcovina, S. M. Barrett-Connor, E. Horton, E. Saudek, C. Pi-Sunyer, X. F. Ratner, R. E. Goldberg, R. B. CA Diabet Prevention Program Res Grp TI Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance SO DIABETES OBESITY & METABOLISM LA English DT Article DE cardiometabolic risk; diabetes prevention; lifestyle; metformin ID PREVENTION-PROGRAM; CARDIOVASCULAR-DISEASE; CARDIOMETABOLIC RISK; INSULIN-RESISTANCE; ABDOMINAL OBESITY; PULSE PRESSURE; MELLITUS; TRIAL; HYPERTENSION; DEFINITION AB AimsTo determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. MethodsWe used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2years. ResultsIn an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. ConclusionsMetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence. C1 [Florez, H.] Univ Miami, Miller Sch Med, Ctr Geriatr Res Educ & Clin, Miami Vet Affairs Healthcare Syst, Miami, FL 33136 USA. [Florez, H.] Univ Miami, Miller Sch Med, Div Epidemiol, Miami, FL 33136 USA. [Florez, H.] Univ Miami, Miller Sch Med, Div Geriatr Med, Miami, FL 33136 USA. [Florez, H.] Univ Miami, Miller Sch Med, Div Endocrinol, Miami, FL 33136 USA. [Temprosa, M. G.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Orchard, T. J.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Mather, K. J.] Indiana Univ Sch Med, Div Endocrinol & Metab, Indianapolis, IN 46202 USA. [Marcovina, S. M.] Univ Washington, NW Lipid Res Labs, Seattle, WA 98195 USA. [Barrett-Connor, E.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Horton, E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Saudek, C.] Johns Hopkins Sch Med, Baltimore, MD USA. [Pi-Sunyer, X. F.] Columbia Univ Coll Phys & Surg, Dept Med, Div Endocrinol Diabet & Nutr, St Lukes Roosevelt Hosp Ctr, New York, NY 10032 USA. [Ratner, R. E.] Medstar Hlth Res Inst, Hyattsville, MD USA. [Goldberg, R. B.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA. RP Florez, H (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Biostat Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu OI orchard, trevor/0000-0001-9552-3215 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; University of Miami [CTSA/1R18AE000049-01/VA-GRECC]; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; McKesson BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson Foundation; Coordinating Centre FX The investigators gratefully acknowledge the commitment and dedication of the participants of the DPP. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centres and the Coordinating Centre for the design and conduct of the study, and collection, management, analysis and interpretation of the data (U01 DK048489). This work was also supported in part by the Intramural Research Program of the NIDDK and the University of Miami CTSA/1R18AE000049-01/VA-GRECC. The General Clinical Research Center Program, National Center for Research Resources and the Department of Veterans Affairs supported data collection at many of the clinical centres. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centres. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. LifeScan Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co. and Quaker Oats Co. donated materials, equipment or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc. and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Centre. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. A complete list of centres, investigators and staff can be found in the Appendix. NR 31 TC 4 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD APR PY 2014 VL 16 IS 4 BP 326 EP 333 DI 10.1111/dom.12220 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8NE UT WOS:000332046500005 PM 24118860 ER PT J AU Josephson, K Ricardo, A Szostak, JW AF Josephson, Kristopher Ricardo, Alonso Szostak, Jack W. TI mRNA display: from basic principles to macrocycle drug discovery SO DRUG DISCOVERY TODAY LA English DT Review ID AMINOACYL-TRANSFER-RNAS; IN-VITRO SELECTION; ELONGATION-FACTOR TU; CYCLIC-PEPTIDES; RIBOSOMAL SYNTHESIS; N-METHYLATION; UNNATURAL PEPTIDES; TRANSLATION; BINDING; PERMEABILITY AB We describe a new discovery technology that uses mRNA-display to rapidly synthesize and screen macrocyclic peptide libraries to explore a valuable region of chemical space typified by natural products. This technology allows high-affinity peptidic macrocycles containing modified backbones and unnatural side chains to be readily selected based on target binding. Success stories covering the first examples of these libraries suggest that they could be used for the discovery of intracellular protein-protein interaction inhibitors, highly selective enzyme inhibitors or synthetic replacements for monoclonal antibodies. The review concludes with a look to the future regarding how this technology might be improved with respect to library design for cell permeability and bioavailability. C1 [Josephson, Kristopher; Ricardo, Alonso] Ra Pharmaceut, Cambridge, MA 02139 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA USA. EM szostak@molbio.mgh.harvard.edu NR 55 TC 25 Z9 26 U1 7 U2 45 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD APR PY 2014 VL 19 IS 4 BP 388 EP 399 DI 10.1016/j.drudis.2013.10.011 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5UL UT WOS:000336196500007 PM 24157402 ER PT J AU Desgagne, V Hivert, MF St-Pierre, J Guay, SP Baillargeon, JP Perron, P Gaudet, D Brisson, D Bouchard, L AF Desgagne, Veronique Hivert, Marie-France St-Pierre, Julie Guay, Simon-Pierre Baillargeon, Jean-Patrice Perron, Patrice Gaudet, Daniel Brisson, Diane Bouchard, Luigi TI Epigenetic dysregulation of the IGF system in placenta of newborns exposed to maternal impaired glucose tolerance SO EPIGENOMICS LA English DT Article DE DNA methylation; gestational diabetes; IGF; mRNA; placenta ID GESTATIONAL DIABETES-MELLITUS; FETAL-GROWTH RESTRICTION; DNA METHYLATION; INCREASING PREVALENCE; FETOPLACENTAL GROWTH; HOUSEKEEPING GENES; INSULIN; EXPRESSION; DISEASE; DESIGNS AB Aims: To determine whether placental IGF1R, IGFBP3, INSR and IGF1 DNA methylation and mRNA levels were dysregulated when exposed to maternal impaired glucose tolerance (IGT) and investigate whether the epigenetic profile is associated with feto-placental developmental markers. Patients & methods: The IGT diagnosis was made according to the WHO criteria (IGT: n = 34; normal glucose tolerance [NGT]: n = 106). DNA methylation and mRNA levels were quantified using bisulfite pyrosequencing and qRT-PCR, respectively. Results:IGF1R and IGFBP3 DNA methylation levels were lower in placentas exposed to IGT compared with NGT (-4.3%; p = 0.021 and -2.5%; p = 0.006 respectively) and correlated with 2-h post-oral glucose tolerance test (OGTT) glycemia (r = -0.23; p = 0.010 and r = -0.20; p = 0.028, respectively). IGF1R mRNA levels were associated with newborns' growth markers (e.g., birth weight; r = 0.20; p = 0.032). Conclusion: These results support the growth-promoting role of the IGF system in placental/fetal development and suggest that the IGF1R and IGFBP3 DNA methylation profiles are dysregulated in IGT, potentially affecting the fetal metabolic programming. C1 [Desgagne, Veronique; Guay, Simon-Pierre; Bouchard, Luigi] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Desgagne, Veronique; St-Pierre, Julie; Guay, Simon-Pierre; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, ECOGENE Clin Res 21, Saguenay, PQ, Canada. [Hivert, Marie-France; Baillargeon, Jean-Patrice; Perron, Patrice] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [St-Pierre, Julie] Chicoutimi Hosp, Dept Pediat, Saguenay, PQ, Canada. [St-Pierre, Julie] Univ Quebec Chicoutimi, Dept Hlth Sci, Saguenay, PQ, Canada. [Gaudet, Daniel; Brisson, Diane] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP Bouchard, L (reprint author), Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. EM luigi.bouchard@usherbrooke.ca FU ECOGENE-21 Clinical research center; Canadian Institutes of Health Research (CIHR); Fonds de Recherche du Quebec en Sante (FRQS); Diabete Quebec; Faculte de medecine et des sciences de la sante (FMSS) of Universite de Sherbrooke; Canadian Diabetes Association clinical scientist award; FRQS; CIHR FX This study was supported by the ECOGENE-21 Clinical research center (principal investigator: D Gaudet, Universite de Montreal), the Canadian Institutes of Health Research (CIHR), the Fonds de Recherche du Quebec en Sante (FRQS) and Diabete Quebec. V Desgagne was supported by Diabete Quebec and by the Faculte de medecine et des sciences de la sante (FMSS) of Universite de Sherbrooke. L Bouchard and M-F Hivert are junior research scholars from the FRQS. M-F Hivert. is also supported by a Canadian Diabetes Association clinical scientist award. L Bouchard and M-F Hivert are members of the FRQS-funded Centre de recherche clinique Etienne-Le Bel (affiliated with Centre Hospitalier de l'Universite de Sherbrooke). During this research, S-P Guay was recipient of a doctoral research award from the CIHR. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 45 TC 9 Z9 9 U1 1 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-1911 EI 1750-192X J9 EPIGENOMICS-UK JI Epigenomics PD APR PY 2014 VL 6 IS 2 BP 193 EP 207 DI 10.2217/epi.14.3 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA AG8RC UT WOS:000335684900009 PM 24811788 ER PT J AU Bhama, PK Hadlock, TA AF Bhama, Prabhat K. Hadlock, Tessa A. TI Contemporary Facial Reanimation SO FACIAL PLASTIC SURGERY LA English DT Article DE facial paralysis; facial nerve; reanimation ID PARALYSIS; NERVE; VALIDATION; MANAGEMENT; SYNKINESIS; SCALE; TOXIN; FACE AB The facial nerve is the most commonly paralyzed nerve in the human body. Facial paralysis affects aesthetic appearance, and it has a profound effect on function and quality of life. Management of patients with facial paralysis requires a multidisciplinary approach, including otolaryngologists, plastic surgeons, ophthalmologists, and physical therapists. Regardless of etiology, patients with facial paralysis should be evaluated systematically, with initial efforts focused upon establishing proper diagnosis. Management should proceed with attention to facial zones, including the brow and periocular region, the midface and oral commissure, the lower lip and chin, and the neck. To effectively compare contemporary facial reanimation strategies, it is essential to employ objective intake assessment methods, and standard reassessment schemas during the entire management period. C1 [Bhama, Prabhat K.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Facial Nerve Ctr, Div Facial Plast & Reconstruct Surg,Dept Otolaryn, Boston, MA 02117 USA. RP Bhama, PK (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Facial Nerve Ctr, Div Facial Plast & Reconstruct Surg,Dept Otolaryn, 243 Charles St,9th Floor, Boston, MA 02117 USA. EM pbhama@gmail.com NR 19 TC 5 Z9 5 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 EI 1098-8793 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD APR PY 2014 VL 30 IS 2 BP 145 EP 151 DI 10.1055/s-0034-1371900 PG 7 WC Surgery SC Surgery GA AH2VY UT WOS:000335981300008 PM 24810125 ER PT J AU Chung, AW Alter, G AF Chung, Amy W. Alter, Galit TI Dissecting the antibody constant region protective immune parameters in HIV infection SO FUTURE VIROLOGY LA English DT Review DE ADCC; antibody; antibody-dependent cellular phagocytosis; antibody-dependent cellular viral inhibition; antibody-dependent complement-dependent cytotoxicity; Fc; Fc effector function; glycosylation; HIV; IgG; subclass ID DEPENDENT CELLULAR CYTOTOXICITY; FC-GAMMA-RECEPTORS; VACCINE EFFICACY TRIAL; HUMAN IMMUNOGLOBULIN-G; SECRETORY IGA; IN-VITRO; ANTIINFLAMMATORY ACTIVITY; MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODY; EFFECTOR-CELLS AB RV144 vaccine immune-correlates analysis has generated a renewed interest in understanding the potentially protective role of non-neutralizing antibodies in HIV infection and vaccine design. Antibodies consist of a variable region involved in antigen binding and a constant region. While both ends of the antibody collaborate to induce protective immunity, it is through the constant portion that an antibody provides instructions to the innate immune system on how the recognized antigen should be processed, contributing directly to antiviral immunity. Antibody constant regions, despite their name, are not uniform structures, but can vary both in protein sequence and glycosylation, together modulating antibody functionality via conformational changes that alter antibody affinity for Fc receptors, complement and so on. This review will focus on how the immune system naturally modulates the Fc domain of antibodies to achieve optimum protective Fc effector responses for vaccine and monoclonal therapeutic design efforts aimed at preventing or curing HIV infection. C1 [Chung, Amy W.; Alter, Galit] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02114 USA. RP Alter, G (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02114 USA. EM galter@mgh.harvard.edu OI Chung, Amy/0000-0003-0020-9704 FU Bill and Melinda Gates Collaboration for AIDS Vaccine Discovery [OPP1032817]; National Health and Medical Research Center [APP1036470]; Massachusetts General Hospital; [NIH1R01AI102660-02]; [5R01Al080289-03] FX This work was supported by: the Bill and Melinda Gates Collaboration for AIDS Vaccine Discovery (OPP1032817: Leveraging Antibody Effector Function); NIH1R01AI102660-02 and 5R01Al080289-03 to G Alter; and National Health and Medical Research Center (APP1036470) and Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery Fellowship to AW Chung. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 150 TC 3 Z9 3 U1 0 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PD APR PY 2014 VL 9 IS 4 BP 397 EP 414 DI 10.2217/fvl.14.19 PG 18 WC Virology SC Virology GA AG6YL UT WOS:000335564900011 ER PT J AU Jilg, N Lin, WY Hong, J Schaefer, EA Wolski, D Meixong, J Goto, K Brisac, C Chusri, P Fusco, DN Chevaliez, S Luther, J Kumthip, K Urban, TJ Peng, LF Lauer, GM Chung, RT AF Jilg, Nikolaus Lin, Wenyu Hong, Jian Schaefer, Esperance A. Wolski, David Meixong, James Goto, Kaku Brisac, Cynthia Chusri, Pattranuch Fusco, Dahlene N. Chevaliez, Stephane Luther, Jay Kumthip, Kattareeya Urban, Thomas J. Peng, Lee F. Lauer, Georg M. Chung, Raymond T. TI Kinetic Differences in the Induction of Interferon Stimulated Genes by Interferon-alpha and Interleukin 28B Are Altered by Infection With Hepatitis C Virus SO HEPATOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; INDUCED VIRAL CLEARANCE; HUMAN HEPATOCYTES; CELL-CULTURE; IL28B; REPLICATION; STAT1; EPIDEMIOLOGY; EXPRESSION; RIBAVIRIN AB Several genome-wide association studies (GWAS) have identified a genetic polymorphism associated with the gene locus for interleukin 28B (IL28B), a type III interferon (IFN), as a major predictor of clinical outcome in hepatitis C. Antiviral effects of the type III IFN family have previously been shown against several viruses, including hepatitis C virus (HCV), and resemble the function of type I IFN including utilization of the intracellular Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. Effects unique to IL28B that would distinguish it from IFN-alpha are not well defined. By analyzing the transcriptomes of primary human hepatocytes (PHH) treated with IFN-alpha or IL28B, we sought to identify functional differences between IFN-alpha and IL28B to better understand the roles of these cytokines in the innate immune response. Although our data did not reveal distinct gene signatures, we detected striking kinetic differences between IFN-alpha and IL28B stimulation for interferon stimulated genes (ISGs). While gene induction was rapid and peaked at 8 hours of stimulation with IFN-alpha in PHH, IL28B produced a slower, but more sustained increase in gene expression. We confirmed these findings in the human hepatoma cell line Huh7.5.1. Interestingly, in HCV-infected cells the rapid response after stimulation with IFN-alpha was blunted, and the induction pattern resembled that caused by IL28B. Conclusion: The kinetics of gene induction are fundamentally different for stimulations with either IFN-alpha or IL28B in hepatocytes, suggesting distinct roles of these cytokines within the immune response. Furthermore, the observed differences are substantially altered by infection with HCV. (Hepatology 2014;59:1250-1261) C1 [Jilg, Nikolaus; Lin, Wenyu; Hong, Jian; Schaefer, Esperance A.; Wolski, David; Meixong, James; Brisac, Cynthia; Chusri, Pattranuch; Fusco, Dahlene N.; Chevaliez, Stephane; Luther, Jay; Kumthip, Kattareeya; Peng, Lee F.; Lauer, Georg M.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Jilg, Nikolaus; Lin, Wenyu; Hong, Jian; Schaefer, Esperance A.; Wolski, David; Meixong, James; Brisac, Cynthia; Chusri, Pattranuch; Fusco, Dahlene N.; Chevaliez, Stephane; Luther, Jay; Kumthip, Kattareeya; Peng, Lee F.; Lauer, Georg M.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Goto, Kaku] Univ Tokyo, Inst Med Sci, Unit Dis Control Genome Med, Tokyo, Japan. [Urban, Thomas J.] Duke Univ, Ctr Human Genome Variat, Durham, NC USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,Warren 1007, Boston, MA 02114 USA. EM rtchung@partners.org FU NIH [N01-DK-7-004/HHSN26l7200700004C] FX The authors thank F. V. Chisari (Scripps Research Institute, La Jolla, CA) for Huh7.5.1 cells, T. Wakita (National Institute for Infectious Diseases, Tokyo, Japan), and Charles M. Rice (Rockefeller University, New York, NY) for the infectious HCV strains JFH1 and Jc1Gluc. Normal human hepatocytes were obtained through the Liver Tissue Cell Distribution System (S. C. Strom, University of Pittsburgh, Pittsburgh, PA) which was funded by NIH Contract # N01-DK-7-004/HHSN26l7200700004C. We thank David Goldstein (Duke University, NC) for facilitating the microarray experiments and T. F. Baumert (INSERM U748, Strasbourg, France) for helpful suggestions. NR 37 TC 23 Z9 24 U1 1 U2 7 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 APR PY 2014 VL 59 IS 4 BP 1250 EP 1261 DI 10.1002/hep.26653 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD4VQ UT WOS:000333249800010 PM 23913866 ER PT J AU Chen, YC Huang, YH Reiberger, T Duyverman, AM Huang, PG Samuel, R Hiddingh, L Roberge, S Koppel, C Lauwers, GY Zhu, AX Jain, RK Duda, DG AF Chen, Yunching Huang, Yuhui Reiberger, Thomas Duyverman, Annique M. Huang, Peigen Samuel, Rekha Hiddingh, Lotte Roberge, Sylvie Koppel, Christina Lauwers, Gregory Y. Zhu, Andrew X. Jain, Rakesh K. Duda, Dan G. TI Differential Effects of Sorafenib on Liver Versus Tumor Fibrosis Mediated by Stromal-Derived Factor 1 Alpha/C-X-C Receptor Type 4 Axis and Myeloid Differentiation Antigen-Positive Myeloid Cell Infiltration in Mice SO HEPATOLOGY LA English DT Article ID HEPATIC STELLATE CELLS; ADVANCED HEPATOCELLULAR-CARCINOMA; GROWTH-FACTOR; PHASE-II; IN-VITRO; ANGIOGENESIS; MICROENVIRONMENT; PATHWAY; CXCR4; EXPRESSION AB Sorafenib-a broad kinase inhibitor-is a standard therapy for advanced hepatocellular carcinoma (HCC) and has been shown to exert antifibrotic effects in liver cirrhosis, a precursor of HCC. However, the effects of sorafenib on tumor desmoplasia-and its consequences on treatment resistance-remain unknown. We demonstrate that sorafenib has differential effects on tumor fibrosis versus liver fibrosis in orthotopic models of HCC in mice. Sorafenib intensifies tumor hypoxia, which increases stromal-derived factor 1 alpha (SDF-1 alpha) expression in cancer and stromal cells and, subsequently, myeloid differentiation antigen-positive (Gr-1(+)) myeloid cell infiltration. The SDF-1 alpha/C-X-C receptor type 4 (CXCR4) pathway directly promotes hepatic stellate cell (HSC) differentiation and activation through the mitogen-activated protein kinase pathway. This is consistent with the association between SDF-1 alpha expression with fibrotic septa in cirrhotic liver tissues as well as with desmoplastic regions of human HCC samples. We demonstrate that after treatment with sorafenib, SDF-1 alpha increased the survival of HSCs and their alpha-smooth muscle actin and collagen I expression, thus increasing tumor fibrosis. Finally, we show that Gr-1(+) myeloid cells mediate HSC differentiation and activation in a paracrine manner. CXCR4 inhibition, using AMD3100 in combination with sorafenib treatment, prevents the increase in tumor fibrosis-despite persistently elevated hypoxia-in part by reducing Gr-1(+) myeloid cell infiltration and inhibits HCC growth. Similarly, antibody blockade of Gr-1 reduces tumor fibrosis and inhibits HCC growth when combined with sorafenib treatment. Conclusion: Blocking SDF-1 alpha/CXCR4 or Gr-1(+) myeloid cell infiltration may reduce hypoxia-mediated HCC desmoplasia and increase the efficacy of sorafenib treatment. (Hepatology 2014;59:1435-1447) C1 [Chen, Yunching; Huang, Yuhui; Reiberger, Thomas; Duyverman, Annique M.; Huang, Peigen; Samuel, Rekha; Hiddingh, Lotte; Roberge, Sylvie; Koppel, Christina; Jain, Rakesh K.; Duda, Dan G.] Harvard Univ, Dept Radiat Oncol, Steele Lab Tumor Biol, Sch Med,Massachusetts Gen Hosp, Boston, MA USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Zhu, Andrew X.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, Steele Lab Tumor Biol, Cox 734,100 Blossom St, Boston, MA 02114 USA. EM duda@steele.mgh.harvard.edu OI Huang, Yuhui/0000-0003-1985-3575 FU National Institutes of Health [P01-CA080124, R01-CA159258, R21-CA139168, R01-CA126642]; National Cancer Institute/Proton Beam Federal Share Program awards; American Cancer Society [120733-RSG-11-073-01-TBG]; Max Kade Fellowship FX This study was supported by the National Institutes of Health grants no.: P01-CA080124, R01-CA159258, R21-CA139168, R01-CA126642 and National Cancer Institute/Proton Beam Federal Share Program awards (to D.G.D. and R.K.J.), by the American Cancer Society grant 120733-RSG-11-073-01-TBG (to D.G.D.) and by a Max Kade Fellowship (to T.R.). NR 50 TC 34 Z9 35 U1 0 U2 16 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 APR PY 2014 VL 59 IS 4 BP 1435 EP 1447 DI 10.1002/hep.26790 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD4VQ UT WOS:000333249800027 PM 24242874 ER PT J AU Granziera, C Daducci, A Romascano, D Roche, A Helms, G Krueger, G Hadjikhani, N AF Granziera, Cristina Daducci, Alessandro Romascano, David Roche, Alexis Helms, Gunther Krueger, Gunnar Hadjikhani, Nouchine TI Structural Abnormalities in the Thalamus of Migraineurs With Aura: A Multiparametric Study at 3 T SO HUMAN BRAIN MAPPING LA English DT Article DE multiparametric MRI; structural MRI; migraine ID MAGNETIZATION-TRANSFER RATIO; PERIAQUEDUCTAL GRAY-MATTER; HUMAN BRAIN; SPREADING DEPRESSION; VENTROPOSTEROMEDIAL NUCLEUS; TRIGEMINOVASCULAR RESPONSES; FUNCTIONAL MRI; IN-VIVO; HEADACHE; MECHANISMS AB Background and objectives: The thalamus exerts a pivotal role in pain processing and cortical excitability control, and migraine is characterized by repeated pain attacks and abnormal cortical habituation to excitatory stimuli. This work aimed at studying the microstructure of the thalamus in migraine patients using an innovative multiparametric approach at high-field magnetic resonance imaging (MRI). Design: We examined 37 migraineurs (22 without aura, MWoA, and 15 with aura, MWA) as well as 20 healthy controls (HC) in a 3-T MRI equipped with a 32-channel coil. We acquired whole-brain T1 relaxation maps and computed magnetization transfer ratio (MTR), generalized fractional anisotropy, and T2* maps to probe microstructural and connectivity integrity and to assess iron deposition. We also correlated the obtained parametric values with the average monthly frequency of migraine attacks and disease duration. Results: T1 relaxation time was significantly shorter in the thalamus of MWA patients compared with MWoA (P < 0.001) and HC (P 0.01); in addition, MTR was higher and T2* relaxation time was shorter in MWA than in MWoA patients (P < 0.05, respectively). These data reveal broad microstructural alterations in the thalamus of MWA patients compared with MWoA and HC, suggesting increased iron deposition and myelin content/cellularity. However, MWA and MWoA patients did not show any differences in the thalamic nucleus involved in pain processing in migraine. Conclusions: There are broad microstructural alterations in the thalamus of MWA patients that may underlie abnormal cortical excitability control leading to cortical spreading depression and visual aura. Hum Brain Mapp 35:1461-1468, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Granziera, Cristina; Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, GRHAD, BMI, SV, CH-1015 Lausanne, Switzerland. [Granziera, Cristina] CHU Vaudois, Dept Clin Neurosci, Lab Rech Neuroimagerie, CH-1011 Lausanne, Switzerland. [Granziera, Cristina] CHU Vaudois, Dept Clin Neurosci, Neuroimmunol Unit, CH-1011 Lausanne, Switzerland. [Granziera, Cristina] Univ Lausanne, Lausanne, Switzerland. [Granziera, Cristina; Daducci, Alessandro; Romascano, David; Roche, Alexis; Krueger, Gunnar] Ecole Polytech Fed Lausanne, Siemens CIBM, Adv Clin Imaging Technol Grp, CH-1015 Lausanne, Switzerland. [Daducci, Alessandro] Ecole Polytech Fed Lausanne, STI IEL LTS5, CH-1015 Lausanne, Switzerland. [Helms, Gunther] Univ Gottingen, MR Forsch Neurol & Psychiat, D-37073 Gottingen, Germany. [Krueger, Gunnar] Siemens Schweiz AG, Healthcare Sect IM&WS S, Renens, Switzerland. [Hadjikhani, Nouchine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Granziera, C (reprint author), EPFL SV BMI GRHAD, Batiment AAB 1 32,Stn 15, CH-1015 Lausanne, Switzerland. EM cristina.granziera@chuv.ch RI Centre d'imagerie Biomedicale, CIBM/B-5740-2012; Helms, Gunther/A-9114-2010; OI Helms, Gunther/0000-0002-1371-5123; Hadjikhani, Nouchine/0000-0003-4075-3106; Granziera, Cristina/0000-0002-4917-8761 FU Swiss National Science Foundation [PZ00P3_131914/1]; Stoicescu Foundation, Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL); Swiss Federal Institute of Technology Lausanne (EPFL); University of Geneva (UniGe); Centre Hospitalier Universitaire Vaudois (CHUV); Hopitaux Universitaires de Geneve (HUG); Leenaards; Jeantet Foundations FX Contract grant sponsor: Swiss National Science Foundation; Contract grant number: PZ00P3_131914/1; Contract grant sponsors: Stoicescu Foundation, Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the University of Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the Hopitaux Universitaires de Geneve (HUG), and the Leenaards and the Jeantet Foundations. NR 44 TC 14 Z9 15 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2014 VL 35 IS 4 BP 1461 EP 1468 DI 10.1002/hbm.22266 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AE9MP UT WOS:000334332200030 PM 23450507 ER PT J AU Pfeiffer, CD Cunningham, MC Poissant, T Furuno, JP Townes, JM Leitz, A Thomas, A Buser, GL Arao, RF Beldavs, ZG AF Pfeiffer, Christopher D. Cunningham, Margaret C. Poissant, Tasha Furuno, Jon P. Townes, John M. Leitz, Andrew Thomas, Ann Buser, Genevieve L. Arao, Robert F. Beldavs, Zintars G. TI Establishment of a Statewide Network for Carbapenem-Resistant Enterobacteriaceae Prevention in a Low-Incidence Region SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID TERM-CARE FACILITIES; KLEBSIELLA-PNEUMONIAE; INFECTION PREVENTION; SPREAD; EMERGENCE; MARYLAND AB Objective.To establish a statewide network to detect, control, and prevent the spread of carbapenem-resistant Enterobacteriaceae (CRE) in a region with a low incidence of CRE infection.Design.Implementation of the Drug Resistant Organism Prevention and Coordinated Regional Epidemiology (DROP-CRE) Network.Setting and participants.Oregon infection prevention and microbiology laboratory personnel, including 48 microbiology laboratories, 62 acute care facilities, and 140 long-term care facilities.Methods.The DROP-CRE working group, comprising representatives from academic institutions and public health, convened an interdisciplinary advisory committee to assist with planning and implementation of CRE epidemiology and control efforts. The working group established a statewide CRE definition and surveillance plan; increased the state laboratory capacity to perform the modified Hodge test and polymerase chain reaction for carbapenemases in real time; and administered surveys that assessed the needs and capabilities of Oregon infection prevention and laboratory personnel. Results of these inquiries informed CRE education and the response plan.Results.Of 60 CRE reported from November 2010 through April 2013, only 3 were identified as carbapenemase producers; the cases were not linked, and no secondary transmission was found. Microbiology laboratories, acute care facilities, and long-term care facilities reported lacking carbapenemase testing capability, reliable interfacility communication, and CRE awareness, respectively. Survey findings informed the creation of the Oregon CRE Toolkit, a state-specific CRE guide booklet.Conclusions.A regional epidemiology surveillance and response network has been implemented in Oregon in advance of widespread CRE transmission. Prospective surveillance will determine whether this collaborative approach will be successful at forestalling the emergence of this important healthcare-associated pathogen. C1 [Pfeiffer, Christopher D.; Townes, John M.] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR 97239 USA. [Pfeiffer, Christopher D.; Leitz, Andrew] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Cunningham, Margaret C.; Poissant, Tasha; Thomas, Ann; Buser, Genevieve L.; Arao, Robert F.; Beldavs, Zintars G.] Oregon Hlth Author, Oregon Publ Hlth Div, Portland, OR USA. [Furuno, Jon P.] Oregon Hlth & Sci Univ, Oregon State Univ, Coll Pharm, Portland, OR 97201 USA. RP Pfeiffer, CD (reprint author), Portland VA Med Ctr, POB 1034 P3 ID, Portland, OR 97239 USA. EM pfeiffec@ohsu.edu OI Poissant, Tasha/0000-0003-4407-272X FU Centers for Disease Control and Prevention Epidemiology and Laboratory Capacity Program through the Affordable Care Act FX Financial support. This work was funded by a cooperative agreement with Centers for Disease Control and Prevention Epidemiology and Laboratory Capacity Program through the Affordable Care Act. NR 19 TC 6 Z9 6 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD APR 1 PY 2014 VL 35 IS 4 SI SI BP 356 EP 361 DI 10.1086/675605 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AC2DP UT WOS:000332308400005 PM 24602939 ER PT J AU Scoville, EA Konijeti, GG Nguyen, DD Sauk, J Yajnik, V Ananthakrishnan, AN AF Scoville, Elizabeth A. Konijeti, Gauree G. Nguyen, Deanna D. Sauk, Jenny Yajnik, Vijay Ananthakrishnan, Ashwin N. TI Venous Thromboembolism in Patients with Inflammatory Bowel Diseases: A Case-control Study of Risk Factors SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE celiac disease; Crohn's disease; ulcerative colitis; thrombosis; prophylaxis ID MEDICALLY ILL PATIENTS; ULCERATIVE-COLITIS; EXTENDED THROMBOPROPHYLAXIS; PULMONARY-EMBOLISM; PROPHYLAXIS; METAANALYSIS; MORTALITY; COHORT; GUIDELINES; THROMBOSIS AB Background:Inflammatory bowel disease (IBD) is a well-known risk factor for venous thromboembolism (VTE). Existing guidelines for thromboprophylaxis in hospitalized patients do not extend to other clinical scenarios that may also be associated with VTE risk. Our aim was to estimate the fraction of VTE events in patients with IBD that could be prevented.Methods:A retrospective analysis assessed all patients with IBD diagnosed with VTE at a single academic medical center from 2002 to 2012. Confirmed cases were analyzed for VTE risk factors, inpatient status, the use of deep venous thrombosis prophylaxis, and when applicable the reason for omission of prophylaxis. IBD VTE cases were compared with age- and sex-matched non-IBD VTE controls with regards to risk factors and potential opportunities for VTE prevention.Results:There were 204 patients with IBD (108 ulcerative colitis, 96 Crohn's disease) diagnosed with VTE (110 deep venous thrombosis, 66 pulmonary embolism, 27 intra-abdominal thromboses, and 1 other). One-third of the VTE events occurred in hospitalized patients. Two-third of the medical inpatients and 44% of surgical inpatients who developed VTE did not receive prophylaxis. Importantly, 129 VTE events occurred in outpatients. The proportion of outpatients hospitalized within 4 weeks of developing venous thrombosis was higher in patients with IBD than non-IBD controls (33% versus 15%, P = 0.0003). One-third (36%) of patients were experiencing ambulatory disease flares at the time of VTE diagnosis.Conclusions:A substantial portion of VTE events in patients with IBD occurred in clinical scenarios is not routinely recommended for thromboprophylaxis. Further investigation of primary prophylaxis for patients with IBD in high-risk outpatients may be warranted. C1 [Scoville, Elizabeth A.; Konijeti, Gauree G.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Konijeti, Gauree G.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institutes of Health (NIH) [P30 DK043351, K23 DK097142] FX Supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. A. N. Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). NR 31 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2014 VL 20 IS 4 BP 631 EP 636 DI 10.1097/MIB.0000000000000007 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AG8EA UT WOS:000335650400008 PM 24552828 ER PT J AU Zhao, X Cao, MQ Feng, HH Fan, H Chen, F Feng, ZJ Li, XS Zhou, XH AF Zhao, Xing Cao, Mingqin Feng, Hai-Huan Fan, Heng Chen, Fei Feng, Zijian Li, Xiaosong Zhou, Xiao-Hua TI Japanese Encephalitis Risk and Contextual Risk Factors in Southwest China: A Bayesian Hierarchical Spatial and Spatiotemporal Analysis SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE Japanese encephalitis; contextual risk factors; meteorological factors; southwest China; Bayesian hierarchical model ID CLIMATE-CHANGE; MALARIA; TRANSMISSION; CHALLENGES; VARIABLES; ECOLOGY; FUTURE; VIRUS AB It is valuable to study the spatiotemporal pattern of Japanese encephalitis (JE) and its association with the contextual risk factors in southwest China, which is the most endemic area in China. Using data from 2004 to 2009, we applied GISmapping and spatial autocorrelation analysis to analyze reported incidence data of JE in 438 counties in southwest China, finding that JE cases were not randomly distributed, and a Bayesian hierarchical spatiotemporal model identified the east part of southwest China as a high risk area. Meanwhile, the Bayesian hierarchical spatial model in 2006 demonstrated a statistically significant association between JE and the agricultural and climatic variables, including the proportion of rural population, the pig-to-human ratio, the monthly precipitation and the monthly mean minimum and maximum temperatures. Particular emphasis was placed on the time-lagged effect for climatic factors. The regression method and the Spearman correlation analysis both identified a two-month lag for the precipitation, while the regression method found a one-month lag for temperature. The results show that the high risk area in the east part of southwest China may be connected to the agricultural and climatic factors. The routine surveillance and the allocation of health resources should be given more attention in this area. Moreover, the meteorological variables might be considered as possible predictors of JE in southwest China. C1 [Zhao, Xing; Feng, Hai-Huan; Fan, Heng; Chen, Fei; Li, Xiaosong] Sichuan Univ, West China Sch Publ Hlth, Chengdu 610041, Peoples R China. [Zhao, Xing; Zhou, Xiao-Hua] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Cao, Mingqin] Xinjiang Med Univ, Sch Publ Hlth, Urumqi 830011, Peoples R China. [Feng, Zijian] Chinese Ctr Dis Control & Prevent China CDC, Off Dis Control & Emergency Response, Beijing 102206, Peoples R China. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. RP Li, XS (reprint author), Sichuan Univ, West China Sch Publ Hlth, Chengdu 610041, Peoples R China. EM zhaoxing731@gmail.com; cmq66@126.com; fenghaihuan@163.com; 13211020002@fudan.edu.cn; jacky2183@163.com; fengzj@chinacdc.cn; lixiaosong1101@126.com; azhou@u.washington.edu FU Natural Science Foundation of China [30571618]; China Scholarship Council FX This study was supported by the Natural Science Foundation of China (No. 30571618) and China Scholarship Council (http://en.csc.edu.cn/). NR 45 TC 4 Z9 4 U1 2 U2 15 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD APR PY 2014 VL 11 IS 4 BP 4201 EP 4217 DI 10.3390/ijerph110404201 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AG9TM UT WOS:000335762700063 PM 24739769 ER PT J AU Dodge, HH Ybarra, O Kaye, JA AF Dodge, Hiroko H. Ybarra, Oscar Kaye, Jeffrey A. TI Tools for advancing research into social networks and cognitive function in older adults SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Editorial Material ID STRESS; SIZE AB People are good for your brain. Decades of research have shown that individuals who have a larger number of people in their social network or higher quality ties with individuals within their network have lower rates of morbidity and mortality across a wide range of health outcomes. Among these outcomes, cognitive function, especially in the context of brain aging, has been one area of particular interest with regard to social engagement, or more broadly, socially integrated lifestyles. Many studies have observed an association between the size of a person's social network or levels of social engagement and the risk for cognitive decline or dementia (e.g. see review by Fratiglioni et al., 2004). The dementia risk reduction associated with a larger social network or social engagement shown by some epidemiological studies is fairly large. The population effect size of increasing social engagement on delaying dementia disease progression could exceed that of current FDA approved medications for Alzheimer's disease. C1 [Dodge, Hiroko H.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Dodge, Hiroko H.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Dodge, Hiroko H.] Univ Michigan Hlth Syst, Dept Neurol, Ann Arbor, MI USA. [Ybarra, Oscar] Univ Michigan, Inst Social Res, Dept Psychol, Res Ctr Grp Dynam, Ann Arbor, MI USA. [Kaye, Jeffrey A.] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. [Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. RP Dodge, HH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. EM dodgeh@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [R01 AG033581, P30 AG008017, P30 AG024978, R01 AG024054]; NIGMS NIH HHS [R01 GM024054] NR 28 TC 8 Z9 8 U1 1 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD APR PY 2014 VL 26 IS 4 BP 533 EP 539 DI 10.1017/S1041610213001750 PG 7 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA AD0MA UT WOS:000332926900002 PM 24152936 ER PT J AU Martinez, P Tsai, AC Muzoora, C Kembabazi, A Weiser, SD Huang, Y Haberer, JE Martin, JN Bangsberg, DR Hunt, PW AF Martinez, Priscilla Tsai, Alexander C. Muzoora, Conrad Kembabazi, Annet Weiser, Sheri D. Huang, Yong Haberer, Jessica E. Martin, Jeffrey N. Bangsberg, David R. Hunt, Peter W. TI Reversal of the Kynurenine Pathway of Tryptophan Catabolism May Improve Depression in ART-Treated HIV-Infected Ugandans SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE tryptophan catabolism; indoleamine 2; 3-dioxygenase-1; depression; antiretroviral therapy; Sub-Saharan Africa ID ACTIVE ANTIRETROVIRAL THERAPY; AIDS-RELATED STIGMA; CD4 CELL COUNT; RURAL UGANDA; INDOLEAMINE 2,3-DIOXYGENASE; FOOD INSECURITY; PATIENT POPULATION; PLASMA TRYPTOPHAN; CLINICAL-PRACTICE; DENDRITIC CELLS AB Background:Major depressive disorder is highly prevalent among HIV-infected persons, and depression symptom severity improves during the course of HIV antiretroviral therapy (ART). The potential biologic pathways explaining these phenomena remain unclear. We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3-dioxygenase-1 and potentially other sources) may correlate with improvements in depression symptom severity in this setting.Method:We used the first year of data from the Uganda AIDS Rural Treatment Outcomes Study, a prospective cohort of 504 HIV-infected individuals initiating their first ART regimen in rural Uganda. We fitted random-effects regression models to estimate the associations between plasma tryptophan, plasma kynurenine, dietary diversity, and self-reported depression symptom severity.Results:Greater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan (KT) ratio over 12-month follow-up. In multivariable-adjusted models, declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity. The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets.Conclusions:Indoleamine 2,3-dioxygenase-1-mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals, particularly among those with poor dietary protein intake. ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms. Interventions to reduce immune activation, and dietary protein supplementation, may be promising strategies to further reduce depression in this setting. C1 [Martinez, Priscilla] Univ Oslo, Norwegian Ctr Addict Res, Oslo, Norway. [Martinez, Priscilla] Univ Calif Berkeley, Sch Publ Hlth, Alcohol Res Grp, Berkeley, CA 94720 USA. [Tsai, Alexander C.; Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Div Global Psychiat, Boston, MA 02114 USA. [Muzoora, Conrad; Kembabazi, Annet; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Weiser, Sheri D.; Huang, Yong; Martin, Jeffrey N.; Hunt, Peter W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Martin, Jeffrey N.; Hunt, Peter W.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Bangsberg, David R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Boston, MA 02115 USA. RP Martinez, P (reprint author), Univ Calif Berkeley, Alcohol Res Grp, 6475 Christie Ave,Suite 400, Emeryville, CA 94608 USA. EM pmartinez@arg.org OI Tsai, Alexander/0000-0001-6397-7917 FU US National Institutes of Health (NIH) [R01MH054907, P30AI27763]; Sullivan Family Foundation FX The Uganda AIDS Rural Treatment Outcomes Study was funded by US National Institutes of Health (NIH) R01MH054907 and P30AI27763, and the Sullivan Family Foundation. NR 62 TC 27 Z9 27 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2014 VL 65 IS 4 BP 456 EP 462 DI 10.1097/QAI.0000000000000062 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AD3PU UT WOS:000333159000018 PM 24220289 ER PT J AU Topalian, SL Sznol, M McDermott, DF Kluger, HM Carvajal, RD Sharfman, WH Brahmer, JR Lawrence, DP Atkins, MB Powderly, JD Leming, PD Lipson, EJ Puzanov, I Smith, DC Taube, JM Wigginton, JM Kollia, GD Gupta, A Pardoll, DM Sosman, JA Hodi, FS AF Topalian, Suzanne L. Sznol, Mario McDermott, David F. Kluger, Harriet M. Carvajal, Richard D. Sharfman, William H. Brahmer, Julie R. Lawrence, Donald P. Atkins, Michael B. Powderly, John D. Leming, Philip D. Lipson, Evan J. Puzanov, Igor Smith, David C. Taube, Janis M. Wigginton, Jon M. Kollia, Georgia D. Gupta, Ashok Pardoll, Drew M. Sosman, Jeffrey A. Hodi, F. Stephen TI Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; SOLID TUMORS; PHASE-II; METASTATIC MELANOMA; ANTI-PD-1 ANTIBODY; B7 FAMILY; IMMUNOTHERAPY; BLOCKADE; IPILIMUMAB; GUIDELINES AB Purpose Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients and Methods Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Results Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Conclusion Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma. C1 [Topalian, Suzanne L.; Sharfman, William H.; Brahmer, Julie R.; Lipson, Evan J.; Taube, Janis M.; Pardoll, Drew M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Sznol, Mario; Kluger, Harriet M.] Yale Univ, Sch Med, New Haven, CT USA. [Sznol, Mario; Kluger, Harriet M.] Yale New Haven Med Ctr, Smilow Canc Ctr, New Haven, CT 06504 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Lawrence, Donald P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carvajal, Richard D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Powderly, John D.] Carolina BioOncol Inst, Huntersville, NC USA. [Leming, Philip D.] Christ Hosp Canc Ctr, Cincinnati, OH USA. [Puzanov, Igor; Sosman, Jeffrey A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Smith, David C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Wigginton, Jon M.; Kollia, Georgia D.; Gupta, Ashok] Bristol Myers Squibb Co, Princeton, NJ USA. RP Topalian, SL (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, 1550 Orleans St,CRB 2,Room 508, Baltimore, MD 21287 USA. EM stopali1@jhmi.edu FU NCI NIH HHS [T32 CA009071, P30 CA006973] NR 38 TC 572 Z9 592 U1 13 U2 83 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2014 VL 32 IS 10 BP 1020 EP + DI 10.1200/JCO.2013.53.0105 PG 12 WC Oncology SC Oncology GA AG0XF UT WOS:000335138400011 PM 24590637 ER PT J AU Holland, JP Liang, SH Rotstein, BH Collier, TL Stephenson, NA Greguric, I Vasdev, N AF Holland, Jason P. Liang, Steven H. Rotstein, Benjamin H. Collier, Thomas L. Stephenson, Nickeisha A. Greguric, Ivan Vasdev, Neil TI Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Review DE Alzheimer's disease; positron emission tomography (PET); A plaque; neuroinflammation; FAAH; GSK-3; MAO-B; tau; acetylcholine esterase; metals ID POSITRON-EMISSION-TOMOGRAPHY; NICOTINIC ACETYLCHOLINE-RECEPTORS; ACID AMIDE HYDROLASE; MONOAMINE-OXIDASE-B; CANNABINOID CB2 RECEPTOR; METABOTROPIC GLUTAMATE RECEPTORS; F-18 LABELED RADIOTRACERS; IN-VIVO EVALUATION; MINI-MENTAL-STATE; CHOLINERGIC HYPOTHESIS AB Alzheimer's disease (AD) and related dementias show increasing clinical prevalence, yet our understanding of the etiology and pathobiology of disease-related neurodegeneration remains limited. In this regard, noninvasive imaging with radiotracers for positron emission tomography (PET) presents a unique tool for quantifying spatial and temporal changes in characteristic biological markers of brain disease and for assessing potential drug efficacy. PET radiotracers targeting different protein markers are being developed to address questions pertaining to the molecular and/or genetic heterogeneity of AD and related dementias. For example, radiotracers including [C-11]-PiB and [F-18]-AV-45 (Florbetapir) are being used to measure the density of A-plaques in AD patients and to interrogate the biological mechanisms of disease initiation and progression. Our focus is on the development of novel PET imaging agents, targeting proteins beyond A-plaques, which can be used to investigate the broader mechanism of AD pathogenesis. Here, we present the chemical basis of various radiotracers which show promise in preclinical or clinical studies for use in evaluating the phenotypic or biochemical characteristics of AD. Radiotracers for PET imaging neuroinflammation, metal ion association with A-plaques, tau protein, cholinergic and cannabinoid receptors, and enzymes including glycogen-synthase kinase-3 and monoamine oxidase B amongst others, and their connection to AD are highlighted. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Holland, Jason P.; Liang, Steven H.; Rotstein, Benjamin H.; Collier, Thomas L.; Stephenson, Nickeisha A.; Vasdev, Neil] Harvard Univ, Sch Med, Div Nucl Med & Mol Imaging, Massachusetts Gen Hosp,Dept Radiol, Boston, MA 02114 USA. [Holland, Jason P.; Greguric, Ivan] Australian Nucl Sci & Technol Org, Life Sci, Kirrawee, NSW 2232, Australia. [Collier, Thomas L.] Advion Inc, Ithaca, NY 14850 USA. RP Vasdev, N (reprint author), Harvard Univ, Sch Med, Div Nucl Med & Mol Imaging, Massachusetts Gen Hosp,Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu OI Holland, Jason/0000-0002-0066-219X; Rotstein, Benjamin/0000-0001-9707-9357 FU Alzheimer's Drug Discovery Foundation FX We gratefully acknowledge financial support from the Alzheimer's Drug Discovery Foundation. We thank Hogger & Co. for graphical abstract and journal cover design. NR 147 TC 15 Z9 15 U1 5 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0362-4803 EI 1099-1344 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 2014 VL 57 IS 4 SI SI BP 323 EP 331 DI 10.1002/jlcr.3158 PG 9 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA AF2KK UT WOS:000334540800022 PM 24327420 ER PT J AU Darragh, TM Wilbur, DC AF Darragh, Teresa M. Wilbur, David C. TI In Reply SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Letter ID LESIONS C1 [Darragh, Teresa M.] Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94143 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Darragh, TM (reprint author), Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94143 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 EI 1526-0976 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD APR PY 2014 VL 18 IS 2 BP E64 EP E65 DI 10.1097/LGT.0b013e3182976077 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AD7PK UT WOS:000333455900010 PM 24670379 ER PT J AU Hart, T Benn, EKT Bagiella, E Arenth, P Dikmen, S Hesdorffer, DC Novack, TA Ricker, JH Zafonte, R AF Hart, Tessa Benn, Emma K. T. Bagiella, Emilia Arenth, Patricia Dikmen, Sureyya Hesdorffer, Dale C. Novack, Thomas A. Ricker, Joseph H. Zafonte, Ross TI Early Trajectory of Psychiatric Symptoms after Traumatic Brain Injury: Relationship to Patient and Injury Characteristics SO JOURNAL OF NEUROTRAUMA LA English DT Article DE longitudinal studies; neurobehavioral signs and symptoms; psychological outcome; traumatic brain injury ID MINOR DEPRESSION; HEALTH OUTCOMES; DISORDERS; PSYCHOPATHOLOGY; FREQUENCY; PATTERNS; VALIDITY; 1-YEAR; RATES AB Psychiatric disturbance is common and disabling after traumatic brain injury (TBI). Few studies have investigated the trajectory of psychiatric symptoms in the first 6 months postinjury, when monitoring and early treatment might prevent persistent difficulties. The aim of this study was to examine the trajectory of psychiatric symptoms 1-6 months post-TBI, the patient/injury characteristics associated with changes, and characteristics predictive of persisting symptoms. A secondary analysis was performed on data from a clinical trial with three data collection points. Across eight centers, 872 participants with complicated mild to severe TBI were administered the Brief Symptom Inventory (BSI) at 30, 90, and 180 days postinjury. Mixed-effects models were used to assess longitudinal changes in the BSI Global Severity Index (GSI). Multi-variate logistic regression was used to assess predictors of clinically significant GSI elevations persisting to 6 months post-TBI. In general, GSI scores improved over time. Women improved faster than men; race/ethnicity was also significantly associated with rate of change, with Hispanics showing the most and African Americans the least improvement. Clinically significant psychiatric symptoms (caseness) occurred in 42% of the sample at 6 months, and more than one type of symptom was common. Significant predictors of caseness included African American race, age from 30 to 60 years, longer post-traumatic amnesia (PTA) duration, pre-TBI unemployment, and pre-TBI risky alcohol use. Findings indicate that psychiatric symptoms are common in the first 6 months post-TBI and frequently extend beyond the depression and anxiety symptoms that may be most commonly screened. Patients with longer PTA and preinjury alcohol misuse may need more intensive monitoring for symptom persistence. C1 [Hart, Tessa] Moss Rehabil Res Inst, Elkins Pk, PA 19027 USA. [Benn, Emma K. T.; Bagiella, Emilia] Icahn Sch Med Mt Sinai, Dept Hlth Evidence & Policy, New York, NY USA. [Benn, Emma K. T.; Bagiella, Emilia] Icahn Sch Med Mt Sinai, Ctr Biostat, New York, NY USA. [Arenth, Patricia; Ricker, Joseph H.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Dikmen, Sureyya] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hesdorffer, Dale C.] Columbia Univ, GH Sergievsky Ctr, New York, NY USA. [Novack, Thomas A.] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL USA. [Zafonte, Ross] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. RP Hart, T (reprint author), Moss Rehabil Res Inst, 50 Township Line Rd, Elkins Pk, PA 19027 USA. EM thart@einstein.edu FU NIH (National Institute of Child Health and Human Development/National Center for Medical Rehabilitation Research) [U01 HD042738] FX This work was funded by Cooperative Agreement #U01 HD042738 from the NIH (National Institute of Child Health and Human Development/National Center for Medical Rehabilitation Research). NR 38 TC 9 Z9 9 U1 2 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD APR 1 PY 2014 VL 31 IS 7 BP 610 EP 617 DI 10.1089/neu.2013.3041 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AD7PB UT WOS:000333455000002 PM 24237113 ER PT J AU Ji, JS Schwartz, J Sparrow, D Hu, H Weisskopf, MG AF Ji, John S. Schwartz, Joel Sparrow, David Hu, Howard Weisskopf, Marc G. TI Occupational Determinants of Cumulative Lead Exposure Analysis of Bone Lead Among Men in the VA Normative Aging Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID BLOOD LEAD; ELDERLY-MEN; UNITED-STATES; CARDIOVASCULAR-DISEASE; BRAIN CANCER; HEALTH; POPULATION; WORKERS; HYPERTENSION; COHORT AB Objectives: To examine the relation between occupation and cumulative lead exposureassessed by measuring bone leadin a community-dwelling population. Method: We measured bone lead concentration with K-shell X-Ray Fluorescence in 1320 men in the Normative Aging Study. We categorized job titles into 14 broad US Census Bureau categories. We used ordinary least squares regression to estimate bone lead by job categories adjusted for other predictors. Results: Service workers, construction, and extractive craft workers and installation, maintenance, and repair craft workers had the highest bone lead concentrations. Including occupations significantly improved the overall model (P < 0.001) and reduced by 15% to 81% the association between bone lead and education categories. Conclusion: Occupation significantly predicts cumulative lead exposure in a community-dwelling population and accounts for a large proportion of the association between education and bone lead. C1 [Ji, John S.; Schwartz, Joel; Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Schwartz, Joel; Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Sparrow, David] VA Boston Healthcare Syst, Boston, MA USA. [Sparrow, David] Boston Univ, Sch Publ Hlth & Med, Boston, MA 02215 USA. [Hu, Howard] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. RP Ji, JS (reprint author), Harvard Univ, Sch Publ Hlth, Landmark Ctr, Dept Environm Hlth, 401 Pk Dr,3 East, Boston, MA 02215 USA. EM joj518@mail.harvard.edu OI Hu, Howard/0000-0002-3676-2707 FU Education and Research Center for Occupational Safety and Health CDC/NIOSH at the Harvard School of Public Health [T42/OH008416]; VA Research Center; Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Boston, MA FX John S. Li was supported by the Education and Research Center for Occupational Safety and Health CDC/NIOSH grant award T42/OH008416 at the Harvard School of Public Health. Dr David Sparrow is supported by a VA Research Center Scientist award. The Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Boston, MA. NR 37 TC 2 Z9 2 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD APR PY 2014 VL 56 IS 4 BP 435 EP 440 DI 10.1097/JOM.0000000000000127 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AG6ZJ UT WOS:000335567400022 PM 24709766 ER PT J AU Hurley, SL Strumpf, N Barg, FK Ersek, M AF Hurley, Susan Lysaght Strumpf, Neville Barg, Frances K. Ersek, Mary TI Not Quite Seamless: Transitions between Home and Inpatient Hospice SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CARE; PLACE; LIFE AB Background: Although most hospice care occurs in the home, a growing number of patients utilize inpatient hospice settings. An inpatient hospice stay requires one or more transitions in care settings, although little is known about these transitions. Objective/Design: Using ethnographic methods, this study examined the beliefs and practices of older adults, their caregivers, and hospice interdisciplinary team (IDT) members surrounding transitions between home and inpatient hospice. Setting/Subjects: Data collection took place over 11 months in a large not-for-profit hospice agency in the northeast. Data were collected through 18 observations and 38 semistructured interviews with patients, family caregivers, and hospice IDT members. Results: Transitions from home to inpatient hospice centered on three processes: developing a plan for future needs, identifying triggers that signaled increased needs for care, and navigating through phases of increased care. Patients, family caregivers, or IDT members identified triggers for more care, and actions were taken to respond in the home care setting. Challenges to these actions occurred in many phases of care and when needs were ultimately unable to be addressed at home, patients were transferred to inpatient hospice. Conclusions: Understanding how care planning, increased needs, and phases of care influence decisions about transitioning patients to inpatient hospice can guide IDT members in minimizing transitions and providing a more seamless continuum of hospice care. C1 [Hurley, Susan Lysaght; Ersek, Mary] North Shore Med Ctr, Salem, MA 01970 USA. [Strumpf, Neville] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Barg, Frances K.] Univ Penn, Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Ersek, Mary] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Hurley, SL (reprint author), North Shore Med Ctr, 81 Highland Ave, Salem, MA 01970 USA. EM slysaghthurley@alumni.upenn.edu FU John A. Hartford Building Academic Geriatric Nursing Capacity Scholar Award; Ruth L. Kirschstein Individual NRSA Predoctoral Fellowship [1F31NR013103] FX S. Lysaght Hurley was supported by a John A. Hartford Building Academic Geriatric Nursing Capacity Scholar Award 2010-2013 and a Ruth L. Kirschstein Individual NRSA Predoctoral Fellowship (1F31NR013103). NR 13 TC 3 Z9 3 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD APR 1 PY 2014 VL 17 IS 4 BP 428 EP 434 DI 10.1089/jpm.2013.0359 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AE2OF UT WOS:000333811900012 ER PT J AU Long, AC Engelberg, RA Downey, L Kross, EK Reinke, LF Feemster, LC Dotolo, D Ford, DW Back, AL Curtis, JR AF Long, Ann C. Engelberg, Ruth A. Downey, Lois Kross, Erin K. Reinke, Lynn F. Feemster, Laura Cecere Dotolo, Danae Ford, Dee W. Back, Anthony L. Curtis, J. Randall TI Race, Income, and Education: Associations with Patient and Family Ratings of End-of-Life Care and Communication Provided by Physicians-in-Training SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HEALTH-CARE; PERCEIVED DISCRIMINATION; SOCIOECONOMIC-STATUS; SEVERE COPD; QUALITY; PERSPECTIVES; DISPARITIES; MATTERS; IMPACT; CANCER AB Background: Minority race and lower socioeconomic status are associated with poorer patient ratings of health care quality and provider communication. Objective: To examine the association of race/ethnicity or socioeconomic status with patients' and families' ratings of end-of-life care and communication about end-of-life care provided by physicians-in-training. Methods: As a component of a randomized trial evaluating a program designed to improve clinician communication about end-of-life care, patients and patients' families completed preintervention survey data regarding care and communication provided by internal medicine residents and medical subspecialty fellows. We examined associations between patient and family race or socioeconomic status and ratings they gave trainees on two questionnaires: the Quality of End-of-Life Care (QEOLC) and Quality of Communication (QOC). Results: Patients from racial/ethnic minority groups, patients with lower income, and patients with lower educational attainment gave trainees higher ratings on the end-of-life care subscale of the QOC (QOCeol). In path models, patient educational attainment and income had a direct effect on outcomes, while race/ethnicity did not. Lower family educational attainment was also associated with higher trainee ratings on the QOCeol, while family non-white race was associated with lower trainee ratings on the QEOLC and general subscale of the QOC. Conclusions: Patient race is associated with perceptions of the quality of communication about end-of-life care provided by physicians-in-training, but the association was opposite to our hypothesis and appears to be mediated by socioeconomic status. Family member predictors of these perceptions differ from those observed for patients. Further investigation of these associations may guide interventions to improve care delivered to patients and families. C1 [Long, Ann C.; Engelberg, Ruth A.; Downey, Lois; Kross, Erin K.; Feemster, Laura Cecere; Dotolo, Danae; Curtis, J. Randall] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Reinke, Lynn F.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Sch Nursing, Seattle, WA 98104 USA. [Back, Anthony L.] Univ Washington, Div Med Oncol, Dept Med, Seattle, WA 98104 USA. [Reinke, Lynn F.; Feemster, Laura Cecere] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Ford, Dee W.] Med Univ S Carolina, Dept Med, Div Pulm & Crit Care Med, Charleston, SC 29425 USA. RP Long, AC (reprint author), Univ Washington, Harborview Med Ctr, 325 9th Ave,Box 359762, Seattle, WA 98104 USA. EM along11@uw.edu FU NIH-NINR [R01NR009987]; NIH-NHLBI [T32 HL007287]; TPM [61-037] FX Funding provided by: NIH-NINR R01NR009987, NIH-NHLBI T32 HL007287, TPM 61-037 NR 30 TC 4 Z9 4 U1 1 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD APR 1 PY 2014 VL 17 IS 4 BP 435 EP 447 DI 10.1089/jpm.2013.0214 PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AE2OF UT WOS:000333811900013 PM 24592958 ER PT J AU Jacobsen, J Kvale, E Rabow, M Rinaldi, S Cohen, S Weissman, D Jackson, V AF Jacobsen, Juliet Kvale, Elizabeth Rabow, Michael Rinaldi, Simone Cohen, Susan Weissman, David Jackson, Vicki TI Helping Patients with Serious Illness Live Well through the Promotion of Adaptive Coping: A Report from the Improving Outpatient Palliative Care ( IPAL-OP) Initiative SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PROBLEM-SOLVING THERAPY; CELL LUNG-CANCER; CONTROLLED-TRIAL; END; LIFE; INTERVENTION; PERCEPTIONS; AWARENESS; PROJECT; HEALTH AB Continuity outpatient palliative care practice is characterized by long relationships between patients, families, and palliative care clinicians and by periods of relative stability when the disease and resultant symptoms are less active. Compared to inpatient palliative care, outpatient practice requires a greater focus on encouraging healthy coping and on helping patients to live well with serious illness. This paper discusses the opportunities to promote adaptive coping in the delivery of outpatient palliative care. C1 [Jacobsen, Juliet; Rinaldi, Simone; Jackson, Vicki] Massachusetts Gen Hosp, Dept Palliat Care, Boston, MA 02114 USA. [Kvale, Elizabeth] Univ Alabama Birmingham, Ctr Palliat & Support Care, Birmingham, AL USA. [Rabow, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Cohen, Susan] NYU, Dept Gen Internal Med, New York, NY USA. [Weissman, David] Ctr Adv Palliat Care, New York, NY USA. [Weissman, David] Med Coll Wisconsin, Dept Neoplast Dis, Milwaukee, WI 53226 USA. RP Jacobsen, J (reprint author), Massachusetts Gen Hosp, Dept Palliat Care, 55 Fruit St,Founders 600, Boston, MA 02114 USA. EM jjacobsen@partners.org NR 31 TC 0 Z9 0 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD APR 1 PY 2014 VL 17 IS 4 BP 463 EP 468 DI 10.1089/jpm.2013.0254 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AE2OF UT WOS:000333811900016 PM 24579823 ER PT J AU Rork, JF Margossian, SP Nambudiri, VE Huang, JT AF Rork, Jillian F. Margossian, Steven P. Nambudiri, Vinod E. Huang, Jennifer T. TI Nonmelanoma Skin Cancer in Childhood After Hematopoietic Stem Cell Transplant: A Report of 4 Cases SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE nonmelanoma skin cancer; hematopoietic stem cell transplant; graft-versus-host disease; voriconazole ID VORICONAZOLE; IRRADIATION; RECIPIENTS; CARCINOMA; SURVIVORS AB Although it is known that hematopoietic stem cell transplantation (HSCT) survivors are at risk of nonmelanoma skin cancer (NMSC), there is limited literature on the incidence of NMSC during childhood in this population. We present 4 HSCT patients ages 13 to 20 years diagnosed with NMSC in our clinic over a 1-year period. Each patient had multiple risk factors associated with NMSC including chronic graft-versus-host disease, prolonged immunosuppression, total-body irradiation, and voriconazole therapy. We conclude that the incidence of NMSC in children after HSCT may be underestimated and should be further investigated. Appropriate skin cancer screening, including annual skin examinations, are advised for pediatric patients with identifiable risk factors. C1 [Rork, Jillian F.; Huang, Jennifer T.] Harvard Univ, Sch Med, Dermatol Program, Boston Childrens Hosp, Boston, MA 02115 USA. [Margossian, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp,Dept Hematol Oncol, Boston, MA 02115 USA. [Nambudiri, Vinod E.] Harvard Univ, Sch Med, Dept Dermatol, Harvard Combined Dermatol Residency Program, Boston, MA 02115 USA. RP Huang, JT (reprint author), Harvard Univ, Sch Med, Dermatol Program, Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM jennifer.huang@childrens.harvard.edu NR 15 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD APR PY 2014 VL 36 IS 3 BP 224 EP 227 DI 10.1097/MPH.0b013e31828e5d96 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AG3XE UT WOS:000335352400027 PM 23619124 ER PT J AU Kenney, LB Duffey-Lind, E Ebb, D Sklar, CA Grier, H Diller, L AF Kenney, Lisa B. Duffey-Lind, Eileen Ebb, David Sklar, Charles A. Grier, Holcombe Diller, Lisa TI Impaired Testicular Function After an Ifosfamide-containing Regimen for Pediatric Osteosarcoma: A Case Series and Review of the Literature SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE ifosfamide; infertility; Leydig cell dysfunction; osteosarcoma; cancer survivor ID LEYDIG-CELL DYSFUNCTION; COMBINATION CHEMOTHERAPY; FERTILITY PRESERVATION; CHILDHOOD-CANCER; SURVIVORS; IMPACT; RISK; CYCLOPHOSPHAMIDE; MEN AB To assess testicular function after standard dose ifosfamide, we evaluated 6 young adult osteosarcoma survivors (median age at diagnosis, 16.5 y; median follow-up, 4 y) treated with ifosfamide (median dose, 45.5 g/m(2)) as part of a chemotherapy regimen (adriamycin/cisplatin/methotrexate/ifosfamide/+/- muramyl-tripeptide-phosphatidyl-ethanolamine). Four of 6 survivors (67%) had abnormal semen analysis (2 oligospermic, 2 azoospermic). Of those, 1/4 had reduced testicular volume, and 2/3 elevated FSH levels. All reported adequate sexual function, 6/6 had normal testosterone levels, but 4/6 had elevated LH levels. Ifosfamide exposure in the context of this regimen was associated with a high likelihood of impaired spermatogenesis and Leydig cell insufficiency. C1 [Kenney, Lisa B.; Duffey-Lind, Eileen; Grier, Holcombe; Diller, Lisa] Boston Childrens Hosp, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02215 USA. [Ebb, David] Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. [Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Kenney, LB (reprint author), Boston Childrens Hosp, Dept Pediat, Dana Farber Canc Inst, D321,450 Brookline Ave, Boston, MA 02215 USA. EM lisa_kenney@dfci.harvard.edu FU Bristol Meyers Squibb; Novo Nordisk FX Supported by Bristol Meyers Squibb.; Dr Sklar was a paid consultant for Novo Nordisk. The remaining authors declare no conflict of interest. NR 19 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD APR PY 2014 VL 36 IS 3 BP 237 EP 240 DI 10.1097/MPH.0b013e3182a27c39 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AG3XE UT WOS:000335352400031 PM 24667129 ER PT J AU Bengali, R Huang, MS Gulur, P AF Bengali, Raheel Huang, Mary S. Gulur, Padma TI The Use of an Intrathecal Pump to Manage Intractable Cancer Pain in a Pediatric Patient: A Case Report SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE intrathecal therapy; intrathecal pump; pediatric; pain; palliative care ID MORPHINE AB A 15-year-old girl with combined immune deficiency syndrome, diagnosed with metastatic squamous cell cancer of the anus, had significant pain secondary to vulvar-perianal condyloma. Conventional treatment with oral and intravenous analgesics was limited by significant side effects of mental status changes and urinary retention leading to clinical deterioration that precluded attempts at chemotherapy. An intrathecal pump was implanted in the challenging setting of neutropenia. There was a drastic improvement in her quality of life and the ability to tolerate further chemotherapy. The option of an intrathecal pump for pain control extended our patient's ability to enjoy important quality time with family by several months. C1 [Bengali, Raheel; Gulur, Padma] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Huang, Mary S.] Massachusetts Gen Hosp Children, Dept Pediat Hematol & Oncol, Boston, MA USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM pgulur@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD APR PY 2014 VL 36 IS 3 BP E162 EP E164 DI 10.1097/MPH.0b013e31828e5dca PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AG3XE UT WOS:000335352400007 PM 23652866 ER PT J AU Choi, YL Lira, ME Hong, M Kim, RN Choi, SJ Song, JY Pandy, K Mann, DL Stahl, JA Peckham, HE Zheng, ZL Han, J Mao, M Kim, J AF Choi, Yoon-La Lira, Maruja E. Hong, Mineui Kim, Ryong Nam Choi, So-Jung Song, Ji-Young Pandy, Kinnari Mann, Derrick L. Stahl, Joshua A. Peckham, Heather E. Zheng, Zongli Han, Joungho Mao, Mao Kim, Jhingook TI A Novel Fusion of TPR and ALK in Lung Adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; ALK; TPR; Translocation ID ANAPLASTIC LYMPHOMA KINASE; 8P11 MYELOPROLIFERATIVE SYNDROME; NUCLEAR-PORE COMPLEX; PROTEIN; GENE; IDENTIFICATION; TRANSFORMATION; LOCALIZATION; EXPRESSION; CANCER AB Introduction: Anaplastic lymphoma kinase (ALK) fusion is the most common mechanism for overexpression and activation in non-small-cell lung carcinoma. Several fusion partners of ALK have been reported, including echinoderm microtubule-associated protein-like 4, TRK-fused gene, kinesin family member 5B, kinesin light chain 1 (KLC1), protein tyrosine phosphatase and nonreceptor type 3, and huntingtin interacting protein 1 (HIP1). Methods and Results: A 60-year-old Korean man had a lung mass which was a poorly differentiated adenocarcinoma with ALK overexpression. By using an Anchored Multiplex polymerase chain reaction assay and sequencing, we found that tumor had a novel translocated promoter region (TPR)-ALK fusion. The fusion transcript was generated from an intact, in-frame fusion of TPR exon 15 and ALK exon 20 (t(1;2)(q31.1;p23)). The TPR-ALK fusion encodes a predicted protein of 1192 amino acids with a coiled-coil domain encoded by the 5'-2(nd) of the TPR and juxtamembrane and kinase domains encoded by the 3'-end of the ALK. Conclusions: The novel fusion gene and its protein TRP-ALK, harboring coiled-coil and kinase domains, could possess transforming potential and responses to treatment with ALK inhibitors. This case is the first report of TPR-ALK fusion transcript in clinical tumor samples and could provide a novel diagnostic and therapeutic candidate target for patients with cancer, including non-small-cell lung carcinoma. C1 [Choi, Yoon-La; Hong, Mineui] Sungkyunkwan Univ, Dept Pathol, Samsung Med Ctr, Coll Med, Seoul 135710, South Korea. [Choi, So-Jung; Kim, Jhingook] Sungkyunkwan Univ, Dept Thorac Surg, Samsung Med Ctr, Coll Med, Seoul 135710, South Korea. [Choi, Yoon-La; Song, Ji-Young; Han, Joungho] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Lab Canc Genom & Mol Pathol,Samsung Biomed Res In, Seoul, South Korea. [Lira, Maruja E.; Pandy, Kinnari; Mao, Mao] Pfizer Inc, Oncol Res Unit, San Diego, CA USA. [Kim, Ryong Nam] Seoul Natl Univ, Dept Pharm, Coll Pharm, Seoul, South Korea. [Mann, Derrick L.; Stahl, Joshua A.; Peckham, Heather E.] ArcherDx Inc, Boulder, CO USA. [Zheng, Zongli] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zheng, Zongli] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Kim, J (reprint author), Sungkyunkwan Univ, Dept Thorac Surg, Samsung Med Ctr, Sch Med, 50 Ilwon Dong, Seoul 135710, South Korea. EM jhingook-kim@gmail.com RI zheng, zongli/B-2917-2011 OI zheng, zongli/0000-0003-4849-4903 FU National Research Foundation of Korea (NRF) grant; Korea government (MSIP) [NRF-2013R1A2A2A01068922] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2013R1A2A2A01068922). NR 15 TC 15 Z9 15 U1 0 U2 11 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 APR PY 2014 VL 9 IS 4 BP 563 EP 566 DI 10.1097/JTO.0000000000000093 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AD3MO UT WOS:000333145300025 PM 24736082 ER PT J AU Sillesen, M Johansson, PI Rasmussen, LS Jin, G Jepsen, CH Imam, A Hwabejire, JO Deperalta, D Duggan, M deMoya, M Velmahos, GC Alam, HB AF Sillesen, Martin Johansson, Paer I. Rasmussen, Lars S. Jin, Guang Jepsen, Cecilie H. Imam, Ayesha Hwabejire, John O. Deperalta, Danielle Duggan, Michael deMoya, Marc Velmahos, George C. Alam, Hasan B. TI Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Trauma; brain; platelets; endothelium; swine ID MASSIVE TRANSFUSION; BRAIN-INJURY; ENDOTHELIAL-CELLS; HEMORRHAGIC-SHOCK; IN-VITRO; MORTALITY; THROMBOCYTOPENIA; COAGULOPATHY; COAGULATION; INHIBITION AB BACKGROUND Platelet dysfunction following trauma has been identified as an independent predictor of mortality. We hypothesized that fresh frozen plasma (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9% normal saline (NS). METHODS Twelve swine were subjected to multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth factor [TGF-], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity. RESULTS ADP-induced platelet aggregation was significantly higher in the FFP group (46.3 U vs. 25.5 U, p < 0.01) following resuscitation. This was associated with higher fibrinogen levels (202 mg/dL vs. 80 mg/dL, p < 0.01) but lower endothelial activation (VCAM-1, 1.25 ng/mL vs. 3.87 ng/mL, p = 0.05). Other markers did not differ. After 6 hours of observation, ADP-induced platelet aggregation remained higher in the FFP group (53.8 U vs. 37.0 U, p = 0.03) as was fibrinogen levels (229 mg/dL vs. 153 mg/dL, p < 0.01). Endothelial activation was lower (ICAM-1, 21.0 ng/mL vs. 24.4 ng/mL, p = 0.05), whereas TGF- levels were higher (2,138 pg/mL vs. 1,802 pg/mL, p = 0.03) in the FFP group. Other markers did not differ. Thromboelastography revealed increased clot strength in the FFP group at both postresuscitation time points. CONCLUSION Resuscitation with FFP resulted in an immediate and sustained improvement in platelet function and clot strength compared with high-volume NS resuscitation. This was associated with an increase in fibrinogen levels and an attenuation of endothelial activation. C1 [Sillesen, Martin; Jepsen, Cecilie H.; Imam, Ayesha; Hwabejire, John O.; Deperalta, Danielle; Duggan, Michael; deMoya, Marc; Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg,Med Sch, Boston, MA USA. [Sillesen, Martin; Rasmussen, Lars S.] Rigshosp, Copenhagen Univ Hosp, Dept Anesthesia, Copenhagen, Denmark. [Johansson, Paer I.; Jepsen, Cecilie H.] Rigshosp, Copenhagen Univ Hosp, Ctr Head & Orthoped, Copenhagen, Denmark. [Johansson, Paer I.; Jepsen, Cecilie H.] Rigshosp, Copenhagen Univ Hosp, Capital Reg Blood Bank, Copenhagen, Denmark. [Johansson, Paer I.] Univ Texas Houston, Sch Med, Dept Surg, Houston, TX USA. [Jin, Guang; Alam, Hasan B.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu RI Johansson, Par/P-9283-2015; OI Johansson, Par/0000-0001-9778-5964; Rasmussen, Lars/0000-0002-7480-3004 FU US Army Medical Research and Materiel Command [GRANTT00521959]; Copenhagen University Hospital, Rigshospitalet (Denmark); Laerdal Foundation (Norway); Aase and Ejnar Danielsen foundation (Denmark); Olof Norlander foundation (Sweden); Maersk Foundation (Denmark); Tryg Foundation (Denmark); Lundbeck Foundation (Denmark); Polsky family FX The study was funded by a grant from the US Army Medical Research and Materiel Command (GRANTT00521959) to H.B.A. Grants from Copenhagen University Hospital, Rigshospitalet (Denmark), The Laerdal Foundation (Norway), The Aase and Ejnar Danielsen foundation (Denmark), The Olof Norlander foundation (Sweden), and The Maersk Foundation (Denmark) supported the work done by M.S. L.S.R. has received funding from the Tryg Foundation (Denmark). P.I.J. received funding from the Lundbeck Foundation (Denmark). M.De. received funding from the Polsky family. The Multiplate machine was on unconditional loan from US Distributor Diapharma Group, Inc. (West Chester, OH) for the duration of the study, while the TEG-5000 machine was on unconditional loan from Haemonetics Corp. (Braintree, MA). These companies did not participate in study planning, execution, data analysis, or manuscript preparation. NR 29 TC 11 Z9 11 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD APR PY 2014 VL 76 IS 4 BP 998 EP 1007 DI 10.1097/TA.0000000000000193 PG 10 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AE7FF UT WOS:000334161500021 PM 24662863 ER PT J AU Sternfeld, B Guthrie, KA Ensrud, KE LaCroix, AZ Larson, JC Dunn, AL Anderson, GL Seguin, RA Carpenter, JS Newton, KM Reed, SD Freeman, EW Cohen, LS Joffe, H Roberts, M Caan, BJ AF Sternfeld, Barbara Guthrie, Katherine A. Ensrud, Kristine E. LaCroix, Andrea Z. Larson, Joseph C. Dunn, Andrea L. Anderson, Garnet L. Seguin, Rebecca A. Carpenter, Janet S. Newton, Katherine M. Reed, Susan D. Freeman, Ellen W. Cohen, Lee S. Joffe, Hadine Roberts, Melanie Caan, Bette J. TI Efficacy of exercise for menopausal symptoms: a randomized controlled trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Physical activity; Intervention; Hot flashes; Sleep quality; Insomnia symptoms; Mood ID MODERATE-INTENSITY EXERCISE; PHYSICAL-ACTIVITY; SLEEP QUALITY; HOT FLASHES; POSTMENOPAUSAL WOMEN; VASOMOTOR SYMPTOMS; RACIAL-DIFFERENCES; AFRICAN-AMERICAN; WEIGHT-LOSS; HEALTH AB Objective This study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms. Methods Late perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms (VMS) participated in a randomized controlled trial conducted in three sites: 106 women randomized to exercise and 142 women randomized to usual activity. The exercise intervention consisted of individual facility-based aerobic exercise training three times per week for 12 weeks. VMS frequency and bother were recorded on daily diaries at baseline and on weeks 6 and 12. Intent-to-treat analyses compared between-group differences in changes in VMS frequency and bother, sleep symptoms (Insomnia Severity Index and Pittsburgh Sleep Quality Index), and mood (Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7 questionnaire). Results At the end of week 12, changes in VMS frequency in the exercise group (mean change, -2.4 VMS/d; 95% CI, -3.0 to -1.7) and VMS bother (mean change on a four-point scale, -0.5; 95% CI, -0.6 to -0.4) were not significantly different from those in the control group (-2.6 VMS/d; 95% CI, -3.2 to -2.0; P = 0.43; -0.5 points; 95% CI, -0.6 to -0.4; P = 0.75). The exercise group reported greater improvement in insomnia symptoms (P = 0.03), subjective sleep quality (P = 0.01), and depressive symptoms (P = 0.04), but differences were small and not statistically significant when P values were adjusted for multiple comparisons. Results were similar when considering treatment-adherent women only. Conclusions These findings provide strong evidence that 12 weeks of moderate-intensity aerobic exercise do not alleviate VMS but may result in small improvements in sleep quality, insomnia, and depression in midlife sedentary women. C1 [Sternfeld, Barbara; Caan, Bette J.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Guthrie, Katherine A.; LaCroix, Andrea Z.; Larson, Joseph C.; Anderson, Garnet L.] Fred Hutchison Canc Res Ctr, Seattle, WA USA. [Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA. [Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Dunn, Andrea L.] Klein Buendel Inc, Denver, CO USA. [Seguin, Rebecca A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA USA. [Reed, Susan D.] Univ Washington, Seattle, WA 98195 USA. [Freeman, Ellen W.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Cohen, Lee S.; Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Roberts, Melanie] Natl Inst Fitness & Sport, Indianapolis, IN USA. RP Sternfeld, B (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Barbara.sternfeld@kp.org FU NIA [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Eunice Kennedy Shriver National Institute of Child Health and Development; National Center for Complementary and Alternative Medicine; Office of Research and Women's Health; Indiana Clinical and Translational Sciences Institute; National Institutes of Health, National Center for Research Resources [UL1 RR025761] FX This study was supported by a cooperative agreement issued by the NIA, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Center for Complementary and Alternative Medicine, and the Office of Research and Women's Health, and by NIA grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700. At the Indiana University site, the project was funded in part with support from the Indiana Clinical and Translational Sciences Institute, funded in part by grant UL1 RR025761 from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award. The omega-3 study supplement (omega-3, n - 3, or polyunsaturated fatty acids) was manufactured as eicosapentaenoic acid and donated, with matching placebo, by Nordic Naturals (Watsonville, CA). NR 52 TC 30 Z9 30 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2014 VL 21 IS 4 BP 330 EP 338 DI 10.1097/GME.0b013e31829e4089 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AX UT WOS:000336214200005 PM 23899828 ER PT J AU Newton, KM Reed, SD Guthrie, KA Sherman, KJ Booth-LaForce, C Caan, B Sternfeld, B Carpenter, JS Learman, LA Freeman, EW Cohen, LS Joffe, H Anderson, GL Larson, JC Hunt, JR Ensrud, KE LaCroix, AZ AF Newton, Katherine M. Reed, Susan D. Guthrie, Katherine A. Sherman, Karen J. Booth-LaForce, Cathryn Caan, Bette Sternfeld, Barbara Carpenter, Janet S. Learman, Lee A. Freeman, Ellen W. Cohen, Lee S. Joffe, Hadine Anderson, Garnet L. Larson, Joseph C. Hunt, Julie R. Ensrud, Kristine E. LaCroix, Andrea Z. TI Efficacy of yoga for vasomotor symptoms: a randomized controlled trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Clinical Trials Network; Vasomotor symptoms; Yoga; Meditation; Menopause; Hot flashes ID HORMONE REPLACEMENT THERAPY; MENOPAUSAL HOT FLASHES; POSTMENOPAUSAL WOMEN; SLEEP QUALITY; PHYSICAL-ACTIVITY; DEPRESSED MOOD; HATHA YOGA; TRANSITION; STRESS; COMPLEMENTARY AB Objective This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms (VMS) frequency and bother. Methods This study was a three-by-two factorial, randomized controlled trial. Eligible women were randomized to yoga (n = 107), exercise (n = 106), or usual activity (n = 142), and were simultaneously randomized to a double-blind comparison of -3 fatty acid (n = 177) or placebo (n = 178) capsules. Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice. Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline, 6 weeks, and 12 weeks. Secondary outcomes included insomnia symptoms (Insomnia Severity Index) at baseline and 12 weeks. Results Among 249 randomized women, 237 (95%) completed 12-week assessments. The mean baseline VMS frequency was 7.4 per day (95% CI, 6.6 to 8.1) in the yoga group and 8.0 per day (95% CI, 7.3 to 8.7) in the usual activity group. Intent-to-treat analyses included all participants with response data (n = 237). There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks (mean difference [yoga - usual activity] from baseline at 6 wk, -0.3 [95% CI, -1.1 to 0.5]; mean difference [yoga - usual activity] from baseline at 12 wk, -0.3 [95% CI, -1.2 to 0.6]; P = 0.119 across both time points). Results were similar for VMS bother. At week 12, yoga was associated with an improvement in insomnia symptoms (mean difference [yoga - usual activity] in the change in Insomnia Severity Index, 1.3 [95% CI, -2.5 to -0.1]; P = 0.007). Conclusions Among healthy women, 12 weeks of yoga class plus home practice, compared with usual activity, do not improve VMS frequency or bother but reduce insomnia symptoms. C1 [Newton, Katherine M.; Sherman, Karen J.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Reed, Susan D.] Univ Washington, Sch Med, Dept Obstet Gynecol, Seattle, WA USA. [Reed, Susan D.] Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA USA. [Guthrie, Katherine A.; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie R.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Data Coordinating Ctr, Seattle, WA 98104 USA. [Booth-LaForce, Cathryn] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Caan, Bette; Sternfeld, Barbara] Kaiser Permanente, Div Res, Med Program Northern Calif, Oakland, CA USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Learman, Lee A.] Indiana Univ Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA. [Freeman, Ellen W.] Univ Penn, Dept Obstet Gynecol, Philadelphia, PA 19104 USA. [Cohen, Lee S.; Joffe, Hadine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ensrud, Kristine E.] VA Med Ctr, Dept Med, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Newton, KM (reprint author), Grp Hlth Res Inst, Suite 1600,1730 Minor Ave, Seattle, WA 98101 USA. EM newton.k@ghc.org FU National Institutes of Health; National Institute on Aging [U01AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Indiana Clinical and Translational Sciences Institute; National Institutes of Health, National Center for Research Resources [UL1RR02571]; Clinical and Translational Sciences Award FX This study was funded by the National Institutes of Health as a cooperative agreement issued by the National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center for Complementary and Alternative Medicine, Office of Research on Women's Health, and grants U01AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700 from the National Institute on Aging. At Indiana University, the project was partly funded by the Indiana Clinical and Translational Sciences Institute, grant UL1RR02571 from the National Institutes of Health, National Center for Research Resources, and Clinical and Translational Sciences Award. NR 61 TC 22 Z9 22 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2014 VL 21 IS 4 BP 339 EP 346 DI 10.1097/GME.0b013e31829e4baa PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AX UT WOS:000336214200006 PM 24045673 ER PT J AU Cohen, LS Joffe, H Guthrie, KA Ensrud, KE Freeman, M Carpenter, JS Learman, LA Newton, KM Reed, SD Manson, JE Sternfeld, B Caan, B Freeman, EW LaCroix, AZ Tinker, LF Booth-LaForce, C Larson, JC Anderson, GL AF Cohen, Lee S. Joffe, Hadine Guthrie, Katherine A. Ensrud, Kristine E. Freeman, Marlene Carpenter, Janet S. Learman, Lee A. Newton, Katherine M. Reed, Susan D. Manson, JoAnn E. Sternfeld, Barbara Caan, Bette Freeman, Ellen W. LaCroix, Andrea Z. Tinker, Lesley F. Booth-LaForce, Cathryn Larson, Joseph C. Anderson, Garnet L. TI Efficacy of omega-3 for vasomotor symptoms treatment: a randomized controlled trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Omega-3; Fish oils; Hot flashes; Vasomotor symptoms; Clinical Trials Network; Menopause ID POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MENOPAUSAL TRANSITION; HOT FLASHES; REPRODUCTIVE HORMONES; EICOSAPENTAENOIC ACID; DEPRESSIVE DISORDER; WOMEN; OMEGA-3-FATTY-ACIDS AB Objective This study aims to determine the efficacy and tolerability of omega-3 fatty acids in reducing vasomotor symptoms (VMS) frequency and bother in perimenopausal and postmenopausal women. Methods This study was a 12-week, three-by-two factorial, randomized controlled trial. Eligible women were randomized to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules, and simultaneously to yoga (n = 107), aerobic exercise (n = 106), or their usual physical activity (n = 142). Participants received 1.8 g of omega-3 daily for 12 weeks. Each capsule contained ethyl eicosapentaenoic acid (425 mg), docosahexaenoic acid (100 mg), and other omega-3s (90 mg). Primary outcomes were VMS frequency and bother. Secondary outcomes included sleep quality (Pittsburgh Sleep Quality Index), insomnia symptoms (Insomnia Severity Index), depressive symptoms (Physician's Health Questionnaire-8), and anxiety (Generalized Anxiety Disorder-7). Results The mean baseline frequency of VMS per day was 7.6 (95% CI, 7.0 to 8.2). After 12 weeks, the reduction in VMS frequency with omega-3 (-2.5; 95% CI, -3.0 to -1.9) did not differ significantly from that with placebo (-2.7; 95% CI, -3.3 to -2.2), with a relative difference of 0.3 fewer hot flashes per day (95% CI, -0.5 to 1.0; P = 0.28). Changes in VMS bother at 12 weeks were also similar between groups, with no relative difference on a four-point scale (95% CI, -0.1 to 0.2; P = 0.36). Omega-3s compared with placebo showed no improvement in self-reported sleep or mood (P > 0.09 for all comparisons). Conclusions Among healthy, sedentary perimenopausal and postmenopausal women, a 12-week treatment with omega-3 does not improve VMS frequency, VMS bother, sleep, or mood compared with placebo. C1 [Cohen, Lee S.; Joffe, Hadine; Freeman, Marlene] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Guthrie, Katherine A.; LaCroix, Andrea Z.; Tinker, Lesley F.; Larson, Joseph C.; Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, MsFLASH Data Coordinating Ctr, Seattle, WA 98104 USA. [Ensrud, Kristine E.] Univ Minnesota, VA Med Ctr, Minneapolis, MN USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Learman, Lee A.] Indiana Univ Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA. [Newton, Katherine M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Reed, Susan D.] Univ Washington, Sch Med, Dept Obstet Gynecol, Seattle, WA USA. [Reed, Susan D.] Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA USA. [Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Sternfeld, Barbara; Caan, Bette] Kaiser Permanente, Div Res, Med Program Northern Calif, Oakland, CA USA. [Freeman, Ellen W.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Booth-LaForce, Cathryn] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM lcohen2@partners.org FU National Institutes of Health [UL1RR02571]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Complementary and Alternative Medicine; Office of Research on Women's Health; National Institute on Aging [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Indiana Clinical and Translational Sciences Institute; National Center for Research Resources; Clinical and Translational Sciences Award FX This study was funded by the National Institutes of Health (as a cooperative agreement issued by the National Institute on Aging), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center for Complementary and Alternative Medicine, Office of Research on Women's Health, and National Institute on Aging (grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700). At Indiana University, the project was partly funded by the Indiana Clinical and Translational Sciences Institute, National Institutes of Health grant UL1RR02571, National Center for Research Resources, and Clinical and Translational Sciences Award. The omega-3 study supplement (omega-3, n - 3, or polyunsaturated fatty acids) was manufactured as ethyl eicosapentaenoic acid and donated, with matching placebo, by Nordic Naturals. NR 26 TC 17 Z9 17 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2014 VL 21 IS 4 BP 347 EP 354 DI 10.1097/GME.0b013e31829e40b8 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AX UT WOS:000336214200007 PM 23982113 ER PT J AU Looby, SE Shifren, J Corless, I Rope, A Pedersen, MC Joffe, H Grinspoon, S AF Looby, Sara E. Shifren, Jan Corless, Inge Rope, Alison Pedersen, Maria C. Joffe, Hadine Grinspoon, Steven TI Increased hot flash severity and related interference in perimenopausal human immunodeficiency virus-infected women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Human immunodeficiency virus; Menopause; Hot flashes; Menopause symptoms; Quality of life ID QUALITY-OF-LIFE; ANTIRETROVIRAL THERAPY; VASOMOTOR SYMPTOMS; MENOPAUSE SYMPTOMS; HIV-INFECTION; DEPRESSIVE SYMPTOMS; MIDLIFE WOMEN; HEALTH; AGE; RISK AB Objective As women with human immunodeficiency virus (HIV) are living longer, more are entering perimenopause. Prior studies suggest that HIV-infected women are more likely to have hot flashes than non-HIV-infected women. However, little is known regarding hot flash severity and hot flash-related interference with daily function, mood, and quality of life in this population. Methods Perimenopausal HIV-infected and non-HIV-infected women matched by age, race, and menstrual patterns completed the Menopause Rating Scale (to assess hot flash severity) and the Hot Flash Related Daily Interference Scale (HFRDIS). Menopause Rating Scale and HFRDIS scores and subscores were compared between the groups. Results Thirty-three HIV-infected women and 33 non-HIV-infected women who were similar in age (median [interquartile range], 47 [45-48] vs 47 [46-49] y), race (64% vs 52% nonwhite, P = 0.32), and menstrual patterns (number of periods in the past year; 5 [4-9] vs 6 [4-10], P = 0.53) were studied. Perimenopausal HIV-infected women reported greater hot flash severity (HIV vs non-HIV: 2 [1-3] vs 1 [0-3], P = 0.03) and hot flash-related interference (HFRDIS total score, 37 [10-60] vs 6 [0-20], P = 0.001). Conclusions Perimenopausal HIV-infected women experience greater hot flash severity and related interference compared with non-HIV-infected perimenopausal women. Increased distress secondary to hot flashes may reduce quality of life and negatively impact important health-promoting behaviors, including adherence to antiretroviral therapy, in HIV-infected women. C1 [Looby, Sara E.; Shifren, Jan; Rope, Alison; Pedersen, Maria C.; Grinspoon, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Corless, Inge] Massachusetts Gen Hosp, Inst Hlth Profess, Charlestown, MA 02114 USA. [Joffe, Hadine] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. RP Looby, SE (reprint author), LON5-207,55 Fruit St, Boston, MA 02114 USA. EM slooby@partners.org OI Corless, Inge/0000-0003-0438-2037 FU Nutrition Obesity Research Center at Harvard [NIH K23 NR011833-01A1, P30-DK040561]; Harvard Catalyst-The Harvard Clinical and Translational Science Center [8UL1TR000170-05]; Harvard University FX This project was funded by grant NIH K23 NR011833-01A1 (S. E. L.) and grant P30-DK040561 from the Nutrition Obesity Research Center at Harvard. This work was supported by Harvard Catalyst-The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic healthcare centers). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. NR 35 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2014 VL 21 IS 4 BP 403 EP 409 DI 10.1097/GME.0b013e31829d4c4c PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AX UT WOS:000336214200015 PM 23820600 ER PT J AU Passarelli, MN Newcomb, PA Makar, KW Burnett-Hartman, AN Phipps, AI David, SP Hsu, L Harrison, TA Hutter, CM Duggan, DJ White, E Chan, AT Peters, U AF Passarelli, Michael N. Newcomb, Polly A. Makar, Karen W. Burnett-Hartman, Andrea N. Phipps, Amanda I. David, Sean P. Hsu, Li Harrison, Tabitha A. Hutter, Carolyn M. Duggan, David J. White, Emily Chan, Andrew T. Peters, Ulrike TI No association between germline variation in catechol-O-methyltransferase and colorectal cancer survival in postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Colorectal cancer; Survival; Catechol-O-methyltransferase; Postmenopausal women ID ESTROGEN PLUS PROGESTIN; SINGLE-NUCLEOTIDE POLYMORPHISMS; HORMONE REPLACEMENT THERAPY; INITIATIVE CLINICAL-TRIAL; BREAST-CANCER; COLON-CANCER; COMT POLYMORPHISMS; GENETIC POLYMORPHISMS; SUSCEPTIBILITY LOCI; DNA-DAMAGE AB Objective Sex steroid hormones play a role in colorectal cancer (CRC) development, but little is known about their influence on tumor progression and metastasis. Because catechol-O-methyltransferase (COMT; 22q11.21) activity is an important component of estrogen-mediated carcinogenesis, we hypothesized that germline variation in COMT may be associated with CRC survival. Methods We identified 10 single nucleotide polymorphisms that tagged variation across two isoforms of COMT in 2,458 women with CRC from the Nurses' Health Study, Postmenopausal Hormones Supplementary Study to the Colon Cancer Family Registry, VITamins And Lifestyle Study, and Women's Health Initiative. All four studies participated in the Genetics and Epidemiology of Colorectal Cancer Consortium. Results During a median follow-up of 7 years across all studies, there were 799 deaths, including 566 deaths from CRC. Based on multiple comparisons, no associations between single nucleotide polymorphisms and CRC-specific or overall survival reached statistical significance, including the well-characterized Val108/158Met polymorphism (rs4680; CRC-specific survival: hazard ratio per minor allele, 1.04; 95% CI, 0.92-1.17; overall survival: hazard ratio per minor allele, 1.01; 95% CI, 0.90-1.14). Conclusions In this large study of women with CRC, we find no evidence that common inherited variation in COMT is associated with survival time after diagnosis. C1 [Passarelli, Michael N.; Newcomb, Polly A.; Makar, Karen W.; Burnett-Hartman, Andrea N.; Phipps, Amanda I.; Hsu, Li; Harrison, Tabitha A.; Hutter, Carolyn M.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Passarelli, Michael N.; Newcomb, Polly A.; White, Emily; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [David, Sean P.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Stanford, CA 94305 USA. [David, Sean P.] SRI Int, Menlo Pk, CA 94025 USA. [Hsu, Li] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Duggan, David J.] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Passarelli, MN (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,M4-B402, Seattle, WA 98109 USA. EM pnewcomb@fhcrc.org OI David, Sean/0000-0002-4922-2603 FU National Institutes of Health, National Cancer Institute [T32CA009168, K05CA152715, U01CA137088, R01CA059045, P01CA087969, P50CA127003, R01CA137178, U24CA074794, R01CA076366, K05CA154337]; National Center for Advancing Translational Sciences [KL2TR000421]; National Institutes of Health, National Heart, Blood, and Lung Institute [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX This work was supported by the National Institutes of Health, National Cancer Institute (T32CA009168 to M.N.P.; K05CA152715 to P.A.N.; U01CA137088 and R01CA059045 to U. P.; P01CA087969, P50CA127003, and R01CA137178 to A. T. C.; U24CA074794 and R01CA076366 to P.A.N.; and K05CA154337 to E. W.), and National Center for Advancing Translational Sciences (KL2TR000421 to A.N.B.-H.). A. T. C. is a Damon Runyon Clinical Investigator. The Women's Health Initiative program was funded by the National Institutes of Health, National Heart, Blood, and Lung Institute, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 52 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2014 VL 21 IS 4 BP 415 EP 420 DI 10.1097/GME.0b013e31829e498d PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AX UT WOS:000336214200017 PM 23880798 ER PT J AU Springer, AM Foster-Schubert, K Morton, GJ Schur, EA AF Springer, Alyse M. Foster-Schubert, Karen Morton, Gregory J. Schur, Ellen A. TI Is there evidence that estrogen therapy promotes weight maintenance via effects on leptin? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Review DE Leptin; Estrogen; Hormone therapy; Obesity ID HORMONE REPLACEMENT THERAPY; NONOBESE POSTMENOPAUSAL WOMEN; INITIATIVE RANDOMIZED-TRIAL; SERUM LEPTIN; BODY-COMPOSITION; PLUS PROGESTIN; TRANSDERMAL ESTRADIOL; BILATERAL OVARIECTOMY; METABOLIC SYNDROME; DOUBLE-BLIND AB Objective Leptin, a hormone secreted by adipocytes, plays a crucial role in regulating energy balance. Estrogen, like leptin, reduces food intake and adiposity while increasing energy expenditure in animals and humans of both sexes through its actions on the central nervous system. We reviewed the literature for studies of the effects of exogenously administered estrogen on serum leptin concentrations and adiposity in women. Methods Using PubMed/Medline, we searched for studies of hormone therapy that enrolled healthy postmenopausal women. Studies were further evaluated to determine if leptin and adiposity were monitored both at baseline and throughout a treatment period of at least 2 months. Results Twenty articles met inclusion criteria. We found no consistent effects of exogenous estrogen on serum leptin concentrations, adiposity, or weight gain. Conclusions Despite suggestive data from animal studies, the current literature does not provide compelling evidence that estrogen therapy attenuates weight gain, alters circulating leptin levels, or improves leptin action in postmenopausal women. C1 [Springer, Alyse M.; Schur, Ellen A.] Univ Washington, Sch Med, Seattle, WA USA. [Foster-Schubert, Karen] Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Foster-Schubert, Karen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Morton, Gregory J.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. [Schur, Ellen A.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. RP Schur, EA (reprint author), Harborview Med Ctr, 325 Ninth Ave,Box 359780, Seattle, WA 98104 USA. EM ellschur@uw.edu FU National Institutes of Health [DK083502]; Diabetes and Endocrinology Research Center [P30DK017047] FX E.A.S. was supported by National Institutes of Health grant DK083502 and a Diabetes and Endocrinology Research Center Pilot and Feasibility Award (P30DK017047). NR 48 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2014 VL 21 IS 4 BP 424 EP 432 DI 10.1097/GME.0000000000000117 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH6AX UT WOS:000336214200019 PM 24149922 ER PT J AU Tan, SW Sasada, T Bershteyn, A Yang, KY Ioji, T Zhang, ZP AF Tan, Songwei Sasada, Tetsuro Bershteyn, Anna Yang, Kunyu Ioji, Tetsuya Zhang, Zhiping TI Combinational delivery of lipid-enveloped polymeric nanoparticles carrying different peptides for anti-tumor immunotherapy SO NANOMEDICINE LA English DT Article DE cancer; immunotherapy; lipid-coated nanoparticle; melanoma; T-cell responses; vaccine antigens ID ANTIGEN-LOSS VARIANTS; PHASE-II TRIAL; DENDRITIC CELLS; T-CELLS; EXOGENOUS ANTIGENS; CELLULAR-IMMUNITY; SUPPRESSOR-CELLS; CANCER-TREATMENT; VACCINES; MELANOMA AB Aim: The authors aimed to investigate whether nanotechnology-based delivery of antigenic peptides is feasible for efficiently inducing anti-tumor cytotoxic T lymphocyte responses through vaccination. Materials & methods: Three different murine melanoma antigens were entrapped in lipid-coated poly(D, L-lactide-co-glycolide) nanoparticles (NPs) by the double emulsion method. Results: The loading efficiency of hydrophilic peptides was greatly improved when lipids were introduced to formulate lipid-coated NPs. The lipid-coated NPs carrying a single peptide and/or combinations of multiple lipid-coated NPs carrying antigenic peptides were characterized in vitro and in vivo in a C57/BL6 (B6) mouse model. Both the single melanoma antigen peptide-loaded NPs and combinational delivery of lipid-coated NPs carrying different peptides could induce antigen-specific T-cell responses. However, single peptide-loaded NPs failed to significantly delay the growth of subcutaneously inoculated B16 melanoma cells in a prophylactic setting. By contrast, the combinational delivery of lipid-coated NPs carrying different peptides significantly suppressed growth of inoculated B16 melanoma cells. C1 [Tan, Songwei; Zhang, Zhiping] Huazhong Univ Sci & Technol, Tongji Sch Pharm, Tongji Med Coll, Wuhan 430030, Peoples R China. [Tan, Songwei; Zhang, Zhiping] Huazhong Univ Sci & Technol, Tongji Med Coll, Natl Engn Res Ctr Nanomed, Wuhan 430030, Peoples R China. [Sasada, Tetsuro; Zhang, Zhiping] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA USA. [Sasada, Tetsuro] Dana Farber Canc Inst, Lab Immunobiol, Boston, MA USA. [Sasada, Tetsuro; Zhang, Zhiping] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Sasada, Tetsuro; Ioji, Tetsuya] Kurume Univ, Sch Med, Dept Immunol & Immunotherapy, Kurume, Fukuoka 8300011, Japan. [Bershteyn, Anna] MIT, Dept Mat Sci & Engn, Boston, MA 02115 USA. [Yang, Kunyu] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Ctr Canc, Wuhan 430030, Peoples R China. RP Zhang, ZP (reprint author), Huazhong Univ Sci & Technol, Tongji Sch Pharm, Tongji Med Coll, Wuhan 430030, Peoples R China. EM zhipingzhang@mail.hust.edu.cn RI zhang, zhiping/H-1786-2011; Tan, Song-wei/H-1789-2011 OI Tan, Song-wei/0000-0002-2986-8968 FU Important National Science and Technology Specific Projects, China (973 Program) [2012CB932500]; NSFC [81241103, 21204024]; Ministry of Education of China [20120142120093]; China Postdoctoral Science Foundation [2013T60722]; Innovative Research Fund; funding for Cancer Vaccine Center at the Dana-Farber Cancer Institute FX This work is supported by the Important National Science and Technology Specific Projects, China (973 Program, 2012CB932500), NSFC (number 81241103 & 21204024), Doctoral Fund of Ministry of Education of China (20120142120093), China Postdoctoral Science Foundation (number 2013T60722), Innovative Research Fund and the funding for Cancer Vaccine Center at the Dana-Farber Cancer Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 52 TC 10 Z9 10 U1 3 U2 43 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PD APR PY 2014 VL 9 IS 5 BP 635 EP 647 DI 10.2217/NNM.13.67 PG 13 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA AH6MZ UT WOS:000336246300013 PM 23905577 ER PT J AU Grubbs, V Wasse, H Vittinghoff, E Grimes, BA Johansen, KL AF Grubbs, Vanessa Wasse, Haimanot Vittinghoff, Eric Grimes, Barbara A. Johansen, Kirsten L. TI Health status as a potential mediator of the association between hemodialysis vascular access and mortality SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE elderly; hemodialysis; mortality; vascular access ID DIALYSIS PATIENTS; ELDERLY-PATIENT; REFER PATIENTS; RISK-FACTORS; FISTULA 1ST; OUTCOMES; PATTERNS; QUESTION; DISEASE AB Background. It is unknown whether the selection of healthier patients for ateriovenous fistula (AVF) placement explains higher observed catheter-associated mortality among elderly hemodialysis patients. Methods. From the United States Renal Data System 2005-2007, we used proportional hazard models to examine 117 277 incident hemodialysis patients aged 67-90 years for the association of initial vascular access type and 5-year mortality after accounting for health status. Health status was defined as functional status at dialysis initiation and number of hospital days within 2 years prior to dialysis initiation. Results. Patients with catheter alone had more limited functional status (25.5 versus 10.8% of those with AVF) and 3-fold more prior hospital days than those with AVF (mean 18.0 versus 5.4). In the unadjusted model, the likelihood of death was higher for arteriovenous grafts (AVG) {Hazard ratio (HR) 1.20 [95% CI (1.16-1.25)], catheter plus AVF [HR 1.34 (1.31-1.38)], catheter plus AVG [HR 1.46 (1.40-1.52)] and catheter only [HR 1.95 (1.90-1.99)]}, compared with AVF (P < 0.001). The association attenuated -23.7% (95% CI -22.0, -25.5) overall (AVF versus all other access types) after adjusting for the usual covariates (including sociodemographics, comorbidities and pre-dialysis nephrology care) {AVG [HR 1.21 (1.17-1.26)], catheter plus AVF [HR 1.27 (1.24-1.30)], catheter plus AVG [HR 1.38 (1.32-1.43)] and catheter only [HR 1.69 (1.66-1.73)], P < 0.001}. Additional adjustment for health status further attenuated the association by another -19.7% (-18.2, -21.3) overall but remained statistically significant < AVG [HR 1.18 (1.13-1.22)], catheter plus AVF [HR 1.20 (1.17-1.23)], catheter plus AVG {HR 1.38 [1.26 (1.21-1.31)]} and catheter only [HR 1.54 (1.50-1.58)], P < 0.001>. Conclusions. The observed attenuation in mortality differences previously attributed to access type alone suggests the existence of selection bias. Nevertheless, the persistence of an apparent survival advantage after adjustment for health status suggests that AVF should still be the access of choice for elderly individuals beginning hemodialysis until more definitive data eliminating selection bias become available. C1 [Grubbs, Vanessa; Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Wasse, Haimanot] Emory Univ, Sch Med, Div Nephrol, Atlanta, GA USA. [Wasse, Haimanot] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Vittinghoff, Eric; Grimes, Barbara A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco Vet Adm Med Ctr, Div Nephrol, San Francisco, CA USA. RP Grubbs, V (reprint author), Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. EM grubbsv@medsfgh.ucsf.edu FU USRDS Nutrition Special Studies Center [N01-DK-7-0005]; National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) [1K23DK093710-01A1]; Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation; NIDDK [N01-DK-7-0005, 1K24DK085153] FX This project was sponsored by the USRDS Nutrition Special Studies Center (N01-DK-7-0005). The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. V. G. was supported by grant 1K23DK093710-01A1 from the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) and by the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation. K.L.J. was supported by contract N01-DK-7-0005 and grant 1K24DK085153 from NIDDK. NR 22 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2014 VL 29 IS 4 BP 892 EP 898 DI 10.1093/ndt/gft438 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA AH4JR UT WOS:000336093700028 PM 24235075 ER PT J AU Gupta, A Christensen, RG Bell, HA Goodwin, M Patel, RY Pandey, M Enuameh, MS Rayla, AL Zhu, C Thibodeau-Beganny, S Brodsky, MH Joung, JK Wolfe, SA Stormo, GD AF Gupta, Ankit Christensen, Ryan G. Bell, Heather A. Goodwin, Mathew Patel, Ronak Y. Pandey, Manishi Enuameh, Metewo Selase Rayla, Amy L. Zhu, Cong Thibodeau-Beganny, Stacey Brodsky, Michael H. Joung, J. Keith Wolfe, Scot A. Stormo, Gary D. TI An improved predictive recognition model for Cys(2)-His(2) zinc finger proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; ONE-HYBRID SYSTEM; DNA RECOGNITION; CRYSTAL-STRUCTURE; IN-VIVO; MEIOTIC RECOMBINATION; REGULATORY ELEMENTS; SEQUENCE FEATURES; GENE-EXPRESSION; OPEN CHROMATIN AB Cys(2)-His(2) zinc finger proteins (ZFPs) are the largest family of transcription factors in higher metazoans. They also represent the most diverse family with regards to the composition of their recognition sequences. Although there are a number of ZFPs with characterized DNA-binding preferences, the specificity of the vast majority of ZFPs is unknown and cannot be directly inferred by homology due to the diversity of recognition residues present within individual fingers. Given the large number of unique zinc fingers and assemblies present across eukaryotes, a comprehensive predictive recognition model that could accurately estimate the DNA-binding specificity of any ZFP based on its amino acid sequence would have great utility. Toward this goal, we have used the DNA-binding specificities of 678 two-finger modules from both natural and artificial sources to construct a random forest-based predictive model for ZFP recognition. We find that our recognition model outperforms previously described determinant-based recognition models for ZFPs, and can successfully estimate the specificity of naturally occurring ZFPs with previously defined specificities. C1 [Gupta, Ankit; Enuameh, Metewo Selase; Rayla, Amy L.; Zhu, Cong; Brodsky, Michael H.; Wolfe, Scot A.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. [Gupta, Ankit; Wolfe, Scot A.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. [Christensen, Ryan G.; Patel, Ronak Y.; Pandey, Manishi; Stormo, Gary D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA. [Bell, Heather A.] Worcester Polytech Inst, Dept Biol & Biochem, Worcester, MA 01609 USA. [Bell, Heather A.] Worcester Polytech Inst, Worcester, MA 01609 USA. [Goodwin, Mathew; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp East, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Goodwin, Mathew; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp East, Ctr Canc Res, Charlestown, MA 02129 USA. [Brodsky, Michael H.] Univ Massachusetts, Sch Med, Dept Mol Med, Worcester, MA 01605 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wolfe, SA (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. EM scot.wolfe@umassmed.edu; stormo@wustl.edu FU U.S. National Institutes of Health (NIH) [GM068110, HG000249, HG004744, GM078369]; U.S. National Institutes of Health (NIH) FX U.S. National Institutes of Health (NIH) [GM068110 to S.A.W., HG000249 to G.D.S., HG004744 to M.H.B. and S.A.W., GM078369 to J.K.J., S.A.W., G.D.S.]. Funding for open access charge: U.S. National Institutes of Health (NIH). NR 110 TC 19 Z9 20 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2014 VL 42 IS 8 BP 4800 EP 4812 DI 10.1093/nar/gku132 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH4JD UT WOS:000336092300014 PM 24523353 ER PT J AU Serrao, E Krishnan, L Shun, MC Li, X Cherepanov, P Engelman, A Maertens, GN AF Serrao, Erik Krishnan, Lavanya Shun, Ming-Chieh Li, Xiang Cherepanov, Peter Engelman, Alan Maertens, Goedele N. TI Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREINTEGRATION COMPLEX-FORMATION; TRANSCRIPTION START SITES; IN-VITRO; STRAND TRANSFER; RETROVIRAL INTEGRASES; TERMINAL DOMAINS; GENETIC ANALYSES; CATALYTIC CORE; HUMAN GENOME AB Retroviruses favor target-DNA (tDNA) distortion and particular bases at sites of integration, but the mechanism underlying HIV-1 selectivity is unknown. Crystal structures revealed a network of prototype foamy virus (PFV) integrase residues that distort tDNA: Ala188 and Arg329 interact with tDNA bases, while Arg362 contacts the phosphodiester backbone. HIV-1 integrase residues Ser119, Arg231, and Lys258 were identified here as analogs of PFV integrase residues Ala188, Arg329 and Arg362, respectively. Thirteen integrase mutations were analyzed for effects on integrase activity in vitro and during virus infection, yielding a total of 1610 unique HIV-1 integration sites. Purine (R)/pyrimidine (Y) dinucleotide sequence analysis revealed HIV-1 prefers the tDNA signature (0)RYXRY(4), which accordingly favors overlapping flexible dinucleotides at the center of the integration site. Consistent with roles for Arg231 and Lys258 in sequence specific and non-specific binding, respectively, the R231E mutation altered integration site nucleotide preferences while K258E had no effect. S119A and S119T integrase mutations significantly altered base preferences at positions -3 and 7 from the site of viral DNA joining. The S119A preference moreover mimicked wild-type PFV selectivity at these positions. We conclude that HIV-1 IN residue Ser119 and PFV IN residue Ala188 contact analogous tDNA bases to effect virus integration. C1 [Serrao, Erik; Krishnan, Lavanya; Shun, Ming-Chieh; Li, Xiang; Engelman, Alan] Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. [Serrao, Erik; Krishnan, Lavanya; Shun, Ming-Chieh; Li, Xiang; Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Cherepanov, Peter; Maertens, Goedele N.] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London W2 1PG, England. [Cherepanov, Peter] Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. RP Maertens, GN (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, St Marys Campus,Norfolk Pl, London W2 1PG, England. EM alan_engelman@dfci.harvard.edu; g.maertens@imperial.ac.uk RI Maertens, Goedele/D-8628-2015; Cherepanov, Peter/F-6859-2010 OI Maertens, Goedele/0000-0002-1963-8026; Cherepanov, Peter/0000-0002-0634-538X FU United States National Institutes of Health (NIH) [AI039394, AI070042]; NIH [T32 AI007245]; Medical Research Council UK [G0900116]; Imperial College London FX United States National Institutes of Health (NIH) [AI039394 and AI070042 to A. E.]; NIH [training grant T32 AI007245 to E. S.]. Medical Research Council UK [G0900116 to P. C.]. Funding for open access charge: Imperial College London. NR 64 TC 22 Z9 22 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2014 VL 42 IS 8 BP 5164 EP 5176 DI 10.1093/nar/gku136 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH4JD UT WOS:000336092300043 PM 24520116 ER PT J AU Nieto-Martinez, R Hamdy, O Marante, D Ines Marulanda, M Marchetti, A Hegazi, RA Mechanick, JI AF Nieto-Martinez, Ramfis Hamdy, Osama Marante, Daniel Ines Marulanda, Maria Marchetti, Albert Hegazi, Refaat A. Mechanick, Jeffrey I. TI Transcultural Diabetes Nutrition Algorithm (tDNA): Venezuelan Application SO NUTRIENTS LA English DT Review DE diabetes; T2D; prediabetes; nutrition; MNT ID ACUTE MYOCARDIAL-INFARCTION; Y GASTRIC BYPASS; MEDITERRANEAN DIET; LIFE-STYLE; AMERICAN ASSOCIATION; LATIN-AMERICAN; RISK-FACTORS; PRIMARY PREVENTION; METABOLIC SYNDROME; CLINICAL-PRACTICE AB Medical nutrition therapy (MNT) is a necessary component of comprehensive type 2 diabetes (T2D) management, but optimal outcomes require culturally-sensitive implementation. Accordingly, international experts created an evidence-based transcultural diabetes nutrition algorithm (tDNA) to improve understanding of MNT and to foster portability of current guidelines to various dysglycemic populations worldwide. This report details the development of tDNA-Venezuelan via analysis of region-specific cardiovascular disease (CVD) risk factors, lifestyles, anthropometrics, and resultant tDNA algorithmic modifications. Specific recommendations include: screening for prediabetes (for biochemical monitoring and lifestyle counseling); detecting obesity using Latin American cutoffs for waist circumference and Venezuelan cutoffs for BMI; prescribing MNT to people with prediabetes, T2D, or high CVD risk; specifying control goals in prediabetes and T2D; and describing regional differences in prevalence of CVD risk and lifestyle. Venezuelan deliberations involved evaluating typical food-based eating patterns, correcting improper dietary habits through adaptation of the Mediterranean diet with local foods, developing local recommendations for physical activity, avoiding stigmatizing obesity as a cosmetic problem, avoiding misuse of insulin and metformin, circumscribing bariatric surgery to appropriate indications, and using integrated health service networks to implement tDNA. Finally, further research, national surveys, and validation protocols focusing on CVD risk reduction in Venezuelan populations are necessary. C1 [Nieto-Martinez, Ramfis] Univ Ctr Occidental Lisandro Alvarado, Sch Med, Dept Physiol, Cardiometab Unit, Barquisimeto 3001, Venezuela. [Hamdy, Osama] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02215 USA. [Marante, Daniel] Ctr Med Docente La Trinidad, Serv Endocrinol, Caracas 1080A, Venezuela. [Ines Marulanda, Maria] Ctr Med Guerra Mendez, Dept Internal Med, Valencia 2001, Venezuela. [Marchetti, Albert] MedERA Inc, New York, NY 10019 USA. [Marchetti, Albert] Univ Med & Dent New Jersey, Dept Prevent Med & Community Hlth, Newark, NJ 07101 USA. [Hegazi, Refaat A.] Abbott Nutr Int, Columbus, OH 43219 USA. [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP Hamdy, O (reprint author), Harvard Univ, Joslin Diabet Ctr, Boston, MA 02215 USA. EM nietoramfis@gmail.com; osama.hamdy@joslin.harvard.edu; daniel.marante@gmail.com; mariainesmarulanda@gmail.com; albertmarchetti@yahoo.com; refaat.hegazi@abbott.com; jeffreymechanick@gmail.com FU Abbott Nutrition; Sanofi-Aventis; GSK; Pfizer; MSD; Novartis; Merck; Roche; Boeringher Inghelheim; Astra-Zeneca; Bayer; BMS; Takeda; Eli Lilly; Abbott Nutrition International FX Ramfis Nieto-Martinez has served as a board member for Abbott Nutrition, Sanofi-Aventis, Astra Zeneca, Bristol-Myers Squibb, Roche and Pfizer; has server as speaker of Abbott Nutrition, Sanofi-Aventis, Astra Zeneca, Bristol-Myers Squibb, GSK, Pfizer, Eli Lilly, MSD, Novartis and Merck; has received funding for travel and accommodations from Abbott Nutrition, Sanofi-Aventis, GSK, Pfizer, MSD, Novartis, Merck and Roche and has received a research grant from Novartis.; Maria Ines Marulanda has served as a board member for Abbott Nutrition, Astra Zeneca and Pfizer; has server as speaker of Abbott Nutrition, Astra Zeneca, Pfizer, Novartis, Roche and Bayer; has received funding for travel and accommodations from Abbott Nutrition, Sanofi-Aventis, Pfizer, Novartis, Boeringher Inghelheim, Astra-Zeneca, Bayer and Roche and has received a research grant from Novartis.; Albert Marchetti has received financial support for research and the development of educational materials from BMS, Abbott Nutrition, Takeda, and Eli Lilly.; Jeffrey Mechanick has received financial support from Abbott Nutrition International for the development of educational presentations. NR 103 TC 5 Z9 5 U1 0 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD APR PY 2014 VL 6 IS 4 BP 1333 EP 1363 DI 10.3390/nu6041333 PG 31 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AG5HJ UT WOS:000335449800001 PM 24699193 ER PT J AU Kulke, MH O'Dorisio, T Yang, QM Jackson, J Jackson, S Boehm, KA Shean, MK Law, L Lapuerta, P Kostelec, J Auguste, P Sommers, R Fleming, D Gelhorn, HL AF Kulke, Matthew H. O'Dorisio, Thomas Yang, Qi M. Jackson, Jessica Jackson, Shanna Boehm, Kristi A. Shean, Mary K. Law, Linda Lapuerta, Pablo Kostelec, Jacqueline Auguste, Priscilla Sommers, Robin Fleming, Doug Gelhorn, Heather L. TI Patient-Reported Symptom Experiences Following Participation in a Study of Telotristat Etiprate for Patients with Carcinoid Tumor and Octreotide-Refractory Diarrhea SO PANCREAS LA English DT Meeting Abstract C1 [Kulke, Matthew H.; Sommers, Robin] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Dorisio, Thomas] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Yang, Qi M.; Jackson, Jessica; Jackson, Shanna; Boehm, Kristi A.; Shean, Mary K.; Law, Linda; Lapuerta, Pablo; Fleming, Doug] Lexicon Pharmaceut Inc, The Woodlands, TX USA. [Kostelec, Jacqueline; Auguste, Priscilla; Gelhorn, Heather L.] United BioSource Corp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 497 EP 498 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800051 ER PT J AU Kulke, MH Strosberg, JR Huynh, L Duh, MS Sahai, V Rademaker, AW Benson, AB AF Kulke, Matthew H. Strosberg, Jonathan R. Lynn Huynh Mei Sheng Duh Sahai, Vaibhav Rademaker, Alfred W. Benson, Al B. TI Dose-Escalation of Octreotide-LAR in Patients With Neuroendocrine Tumors (NET) SO PANCREAS LA English DT Meeting Abstract C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Strosberg, Jonathan R.] H Lee Moffitt Canc Ctr & Res Inst, Dept GI Oncol, Tampa, FL USA. [Lynn Huynh; Mei Sheng Duh] Anal Grp Inc, Boston, MA USA. [Sahai, Vaibhav; Rademaker, Alfred W.; Benson, Al B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 497 EP 497 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800050 ER PT J AU Phan, AT Wolin, EM Chan, J Huang, J Hudson, M Hughes, G Shen, GX Strosberg, JR AF Phan, Alexandria T. Wolin, Edward M. Chan, Jennifer Huang, Jerry Hudson, Michelle Hughes, Gareth Shen, Guoxiang Strosberg, Jonathan R. TI Phase 1 Maximum-Tolerated Dose Study of Pasireotide LAR in Patients with Advanced Neuroendocrine Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Phan, Alexandria T.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wolin, Edward M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Chan, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Huang, Jerry; Hudson, Michelle; Hughes, Gareth; Shen, Guoxiang] Novartis Pharmaceut, Oncol Clin Dev, Florham Pk, NJ USA. [Strosberg, Jonathan R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 501 EP 501 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800061 ER PT J AU Qian, ZR Ter-Minassian, M Chan, JA Hooshmand, SM Brais, LK Lin, XH Christiani, DC Fuchs, CS Ogino, S Kulke, MH AF Qian, Zhi Rong Ter-Minassian, Monica Chan, Jennifer A. Hooshmand, Susanne M. Brais, Lauren K. Lin, Xihong Christiani, David C. Fuchs, Charles S. Ogino, Shuji Kulke, Matthew H. TI Tumor Expression of VEGFA and Its Receptors and Clinical Outcomes in Neuroendocrine Tumors SO PANCREAS LA English DT Meeting Abstract C1 [Qian, Zhi Rong; Ter-Minassian, Monica; Chan, Jennifer A.; Hooshmand, Susanne M.; Brais, Lauren K.; Fuchs, Charles S.; Ogino, Shuji; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Qian, Zhi Rong; Ter-Minassian, Monica; Chan, Jennifer A.; Hooshmand, Susanne M.; Brais, Lauren K.; Fuchs, Charles S.; Ogino, Shuji; Kulke, Matthew H.] Harvard Univ, Sch Med, Boston, MA USA. [Ter-Minassian, Monica] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Lin, Xihong; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 501 EP 502 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800063 ER PT J AU Strosberg, JR Bobiak, S Zornosa, CC Choti, MA Bergsland, EK Benson, AB Bloomston, M Kulke, MH Shah, MH Yao, JC AF Strosberg, Jonathan R. Bobiak, Sarah Zornosa, Carrie C. Choti, Michael A. Bergsland, Emily K. Benson, Al B., III Bloomston, Mark Kulke, Matthew H. Shah, Manisha H. Yao, James C. TI Dosing Patterns for Octreotide LAR in Neuroendocrine Tumor (NET) Patients: NCCN NET Outcomes Database SO PANCREAS LA English DT Meeting Abstract C1 [Strosberg, Jonathan R.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Bobiak, Sarah; Zornosa, Carrie C.] Natl Comprehens Canc Network, Ft Washington, PA USA. [Choti, Michael A.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Bergsland, Emily K.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Bloomston, Mark; Shah, Manisha H.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bloomston, Mark; Shah, Manisha H.] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Bloomston, Mark/E-2767-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD APR PY 2014 VL 43 IS 3 BP 506 EP 506 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AD3SQ UT WOS:000333166800076 ER PT J AU Ostrem, JL Markun, LC Glass, GA Racine, CA Volz, MM Heath, SL de Hemptinne, C Starr, PA AF Ostrem, Jill L. Markun, Leslie C. Glass, Graham A. Racine, Caroline A. Volz, Monica M. Heath, Susan L. de Hemptinne, Coralie Starr, Philip A. TI Effect of frequency on subthalamic nucleus deep brain stimulation in primary dystonia SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Subthalamic nucleus; Deep brain stimulation; Primary dystonia; Frequency ID PRIMARY GENERALIZED DYSTONIA; ADVANCED PARKINSON-DISEASE; CRANIAL-CERVICAL DYSTONIA; GLOBUS-PALLIDUS INTERNUS; STN-DBS; GAIT; PARAMETERS; EFFICACY; IMPACT AB Background: Subthalamic nucleus deep brain stimulation (DBS) is an alternative target choice for treating primary dystonia, but little is known about the most effective programming parameters. Objective: Here we prospectively evaluate the effect of low versus high frequency subthalamic nucleus DBS in patients with predominantly cervical or upper extremity primary dystonia. Methods: Seven patients were stimulated at low frequency stimulation (60 Hz) for the first three months and then switched to high frequency stimulation (130 Hz) until month six. Severity of dystonia was determined by a blinded rater (unaware of the patient's pre or post-operative status) who scored the Burke Fahn Marsden dystonia rating scale movement score (BFMDRS-M) and the Toronto Western Spasmodic Torticollis Rating Scale severity score (TWSTRS-S) preoperatively, three, six, and twelve months post-surgery. Results: Patients had a lower mean improvement of 16.6% in BFMDRS-M and 9.5% in TWSTRS-S at three months using low frequency stimulation compared to a 52.3% (p = 0.018) and 45.2% (p = 0.028), respectively, noted at six months using high frequency stimulation. At 12 months (using 130 Hz), the BFMDRS-M and TWSTRS-S improved by 51.8% (p = 0.022) and 56% (p = 0.034). Patients developed transient dyskinesia (during low and high frequency stimulation) which improved with programming adjustments. Conclusion: This study offers further support of the effectiveness of subthalamic nucleus DBS in the treatment of primary dystonia and finds that high frequency stimulation was more effective than low frequency stimulation. Published by Elsevier Ltd. C1 [Ostrem, Jill L.; Markun, Leslie C.; Glass, Graham A.; Volz, Monica M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94115 USA. [Racine, Caroline A.; de Hemptinne, Coralie; Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Ostrem, Jill L.; Markun, Leslie C.; Glass, Graham A.; Heath, Susan L.; Starr, Philip A.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA 94121 USA. RP Ostrem, JL (reprint author), Univ Calif San Francisco, Dept Neurol, 1635 Divisadero St,5th Floor,Suites 520-530, San Francisco, CA 94115 USA. EM jill.ostrem@ucsf.edu FU Benign Essential Blepharospasm Research Foundation FX This study was supported in part from a grant from the Benign Essential Blepharospasm Research Foundation and from private donors Larry and Kana Miao. NR 31 TC 11 Z9 13 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD APR PY 2014 VL 20 IS 4 BP 432 EP 438 DI 10.1016/j.parkreldis.2013.12.012 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AH7ZV UT WOS:000336354800014 PM 24440061 ER PT J AU Broyles, JM Alrakan, M Ensor, CR Khalifian, S Kotton, CN Avery, RK Brandacher, G Lee, WPA Gordon, CR AF Broyles, Justin M. Alrakan, Mohammed Ensor, Christopher R. Khalifian, Saami Kotton, Camille N. Avery, Robin K. Brandacher, Gerald Lee, W. P. Andrew Gordon, Chad R. TI Characterization, Prophylaxis, and Treatment of Infectious Complications in Craniomaxillofacial and Upper Extremity Allotransplantation: A Multicenter Perspective SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ORGAN-TRANSPLANT RECIPIENTS; COMPOSITE TISSUE ALLOTRANSPLANTATION; SOLID-ORGAN; TACROLIMUS MONOTHERAPY; RENAL-TRANSPLANTATION; CYTOMEGALOVIRUS-INFECTION; BONE-MARROW; LYMPHOPROLIFERATIVE DISORDER; PANCREAS TRANSPLANTATION; ALEMTUZUMAB CAMPATH-1H AB Background: Vascularized composite allotransplants consist of heterogeneous tissues from different germ layers, which include skin, muscle, bone, fat, nerves, and lymph nodes. The antigenic diversity of these tissues, particularly of the highly immunogenic skin component, necessitates potent immunosuppressive regimens similar to that of some solid organ transplants. Indeed, the lifelong, high-dose, multidrug immunosuppressive protocols expose vascularized composite allotransplant recipients to considerable risk of infectious, metabolic, and neoplastic sequelae. In this article, the authors review the infectious risk to patients after vascularized composite allotransplantation, with special attention to the somewhat limited experience with the prophylaxis and treatment of infections after this innovative reconstructive surgery. Methods: A review of the literature was undertaken to elucidate the characterization, prophylaxis, and treatment of all documented infectious complications. Results: Infections in face and hand vascularized composite allotransplants follow a course similar to that of solid organ transplants. Several differences exist, including the unique flora of craniomaxillofacial transplants, the increased risk of donor-derived infections, and the alteration of the risk-to-benefit ratio for cytomegalovirus infections. Conclusions: The patient with a face or limb transplant has many of the same infectious risks as a lung transplant recipient, which include bacterial, viral, and fungal infections. Because of the anatomy, mucosal exposure, and differing donor flora, however, the face or limb transplant is susceptible to invasive diseases from a variety of microbes. C1 [Gordon, Chad R.] Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Div Infect Dis, Dept Med, Baltimore, MD 21287 USA. Univ Pittsburgh, Dept Pharm & Therapeut, Med Ctr, Pittsburgh, PA 15260 USA. Harvard Univ, Div Infect Dis, Dept Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Gordon, CR (reprint author), Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, 601 North Caroline St,8th Floor, Baltimore, MD 21287 USA. EM cgordon@jhmi.edu RI Brandacher, Gerald/L-7540-2016 NR 73 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2014 VL 133 IS 4 BP 543E EP 551E DI 10.1097/PRS.0000000000000015 PG 9 WC Surgery SC Surgery GA AH2YR UT WOS:000335988600011 PM 24675206 ER PT J AU Tessler, O Mattos, D Vorstenbosch, J Jones, D Winograd, JM Liao, EC Austen, WG AF Tessler, Oren Mattos, David Vorstenbosch, Joshua Jones, Daniel Winograd, Jonathan M. Liao, Eric C. Austen, William G., Jr. TI A Methodological Analysis of the Plastic Surgery Cost-Utility Literature Using Established Guidelines SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID QUALITY-OF-LIFE; EPIGASTRIC PERFORATOR FLAP; TOTAL WRIST ARTHROPLASTY; RISK ACCEPTANCE; FACIAL TRANSPLANTATION; RHEUMATOID-ARTHRITIS; BREAST HYPERTROPHY; POSTMASTECTOMY RECONSTRUCTION; REDUCTION MAMMAPLASTY; HAND TRANSPLANTATION AB Background: Cost-utility studies, common in medicine, are rare within plastic surgery despite their capability of measuring the value of procedures by considering the societal costs of improving quality of life. The objectives of this study were to analyze the design quality of the plastic surgery cost-utility literature and to identify areas of needed improvement for future studies. Methods: A scoring tool was constructed based on the Recommendations of the Panel on Cost-Effectiveness in Health and Medicine. A PubMed search through October of 2012 was conducted for English-language plastic surgery utility studies. Articles were selected using two inclusion criteria and evaluated using the scoring tool. Results: A 9-point scoring tool was created, and 37 publications were selected. Their average score was 3 out of 9 points. Thirty studies (81 percent) used population preferences in utility measurements. Fifteen studies (41 percent) measured costs, but only four (11 percent) included indirect costs and only five (14 percent) applied discount rates to calculate the value of treatments over time. Three studies (8 percent) earned zero points. The highest scoring study earned 8 points. Conclusions: The identified studies manifest the potential of cost-utility analyses in plastic surgery. Nonetheless, they are inconsistent in applying established cost-utility guidelines, especially in measuring costs and conducting recommended sensitivity analysis. Following this simple scoring tool can help future studies achieve some necessary improvements. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. McGill Univ, Fac Med, Montreal, PQ H3A 2T5, Canada. RP Mattos, D (reprint author), 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM dmattos@post.harvard.edu NR 57 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2014 VL 133 IS 4 BP 584E EP 592E DI 10.1097/PRS.0000000000000004 PG 9 WC Surgery SC Surgery GA AH2YR UT WOS:000335988600015 PM 24675210 ER PT J AU Figueiredo, JC Hsu, L Hutter, CM Lin, Y Campbell, PT Baron, JA Berndt, SI Jiao, S Casey, G Fortini, B Chan, AT Cotterchio, M Lemire, M Gallinger, S Harrison, TA Le Marchand, L Newcomb, PA Slattery, ML Caan, BJ Carlson, CS Zanke, BW Rosse, SA Brenner, H Giovannucci, EL Wu, KN Chang-Claude, J Chanock, SJ Curtis, KR Duggan, D Gong, J Haile, RW Hayes, RB Hoffmeister, M Hopper, JL Jenkins, MA Kolonel, LN Qu, CH Rudolph, A Schoen, RE Schumacher, FR Seminara, D Stelling, DL Thibodeau, SN Thornquist, M Warnick, GS Henderson, BE Ulrich, C Gauderman, WJ Potter, JD White, E Peters, U AF Figueiredo, Jane C. Hsu, Li Hutter, Carolyn M. Lin, Yi Campbell, Peter T. Baron, John A. Berndt, Sonja I. Jiao, Shuo Casey, Graham Fortini, Barbara Chan, Andrew T. Cotterchio, Michelle Lemire, Mathieu Gallinger, Steven Harrison, Tabitha A. Le Marchand, Loic Newcomb, Polly A. Slattery, Martha L. Caan, Bette J. Carlson, Christopher S. Zanke, Brent W. Rosse, Stephanie A. Brenner, Hermann Giovannucci, Edward L. Wu, Kana Chang-Claude, Jenny Chanock, Stephen J. Curtis, Keith R. Duggan, David Gong, Jian Haile, Robert W. Hayes, Richard B. Hoffmeister, Michael Hopper, John L. Jenkins, Mark A. Kolonel, Laurence N. Qu, Conghui Rudolph, Anja Schoen, Robert E. Schumacher, Fredrick R. Seminara, Daniela Stelling, Deanna L. Thibodeau, Stephen N. Thornquist, Mark Warnick, Greg S. Henderson, Brian E. Ulrich, CorneliaM. Gauderman, W. James Potter, John D. White, Emily Peters, Ulrike CA CCFR GECCO TI Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer SO PLOS GENETICS LA English DT Article ID SUSCEPTIBILITY LOCI; ENVIRONMENT INTERACTION; ASSOCIATION SCAN; COLON-CANCER; RED MEAT; ULCERATIVE-COLITIS; MULTIETHNIC COHORT; METAANALYSIS; FIBER; PROGRESSION AB Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. C1 [Figueiredo, Jane C.; Casey, Graham; Fortini, Barbara; Schumacher, Fredrick R.; Henderson, Brian E.; Gauderman, W. James] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hsu, Li; Lin, Yi; Jiao, Shuo; Harrison, Tabitha A.; Newcomb, Polly A.; Carlson, Christopher S.; Rosse, Stephanie A.; Curtis, Keith R.; Gong, Jian; Qu, Conghui; Stelling, Deanna L.; Thornquist, Mark; Warnick, Greg S.; Ulrich, CorneliaM.; Potter, John D.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Hutter, Carolyn M.; Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cotterchio, Michelle] Canc Care Ontario, Toronto, ON, Canada. [Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Gallinger, Steven] Toronto Gen Hosp, Dept Surg, Univ Hlth Network, Toronto, ON, Canada. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Caan, Bette J.] Kaiser Permanente, Med Care Program, Div Res, Oakland, CA USA. [Zanke, Brent W.] Univ Ottawa, Fac Med, Div Hematol, Ottawa, ON, Canada. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Haile, Robert W.] Stanford Canc Inst, Palo Alto, CA USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Rochester, MN USA. [Ulrich, CorneliaM.] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany. [Ulrich, CorneliaM.] German Canc Res Ctr, Heidelberg, Germany. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Figueiredo, JC (reprint author), Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. EM janefigu@usc.edu; upeters@fhcrc.org RI Hoffmeister, Michael/B-5745-2012; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X FU GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045, R01 CA120582]; CCFR: National Institutes of Health (RFA) [CA-95-011]; National Cancer Institute, National Institutes of Health [U01 CA122839]; National Institutes of Health: Australasian Colorectal Cancer Family Registry [U01 CA097735]; National Institutes of Health: Seattle Colorectal Cancer Family Registry [U01 CA074794]; National Institutes of Health: Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; DACHS: German Research Council (Deutsche Forschungsgemeinschaft [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; DALS: National Institutes of Health [R01 CA48998]; National Institutes of Health [P01 CA 055075, UM1 CA167552, R01 137178, P50 CA 127003]; NHS by the National Institutes of Health [R01 137178, P50 CA 127003, P01 CA 087969]; OFCCR: National Institutes of Health [U01 CA074783]; Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research through Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS FX This work was supported by, GECCO: National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088; R01 CA059045; R01 CA120582). CCFR: National Institutes of Health (RFA # CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR. The following Colon CFR centers contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01 CA097735), Seattle Colorectal Cancer Family Registry (U01 CA074794) and Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). DALS: National Institutes of Health (R01 CA48998 to MLS); HPFS was supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA 127003), and NHS by the National Institutes of Health (R01 137178, P01 CA 087969 and P50 CA 127003,). OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Genetic analyses have been supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M et al. Nat Genet 2007 May; 39(5): 645-9), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L et al. Nat Genet. 2009 Sep; 41(9): 986-90 and Petersen, GM et al Nat Genet. 2010 Mar; 42(3): 224-8), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/)accession numbers 000207v.1p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093 v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (R01 CA076366 to PAN). VITAL: National Institutes of Health (K05 CA154337).; WHI: The WHI program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U. S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 18 Z9 21 U1 4 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004228 DI 10.1371/journal.pgen.1004228 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600015 PM 24743840 ER PT J AU Osorio, A Milne, RL Kuchenbaecker, K Vaclova, T Pita, G Alonso, R Peterlongo, P Blanco, I de la Hoya, M Duran, M Diez, O Cajal, TRY Konstantopoulou, I Martinez-Bouzas, C Conejero, RA Soucy, P McGuffog, L Barrowdale, D Lee, A Arver, B Rantala, J Loman, N Ehrencrona, H Olopade, OI Beattie, MS Domchek, SM Nathanson, K Rebbeck, TR Arun, BK Karlan, BY Walsh, C Lester, J John, EM Whittemore, AS Daly, MB Southey, M Hopper, J Terry, MB Buys, SS Janavicius, R Dorfling, CM van Rensburg, EJ Steele, L Neuhausen, SL Ding, YC Hansen, TVO Jonson, L Ejlertsen, B Gerdes, AM Infante, M Herraez, B Moreno, LT Weitzel, JN Herzog, J Weeman, K Manoukian, S Peissel, B Zaffaroni, D Scuvera, G Bonanni, B Mariette, F Volorio, S Viel, A Varesco, L Papi, L Ottini, L Tibiletti, MG Radice, P Yannoukakos, D Garber, J Ellis, S Frost, D Platte, R Fineberg, E Evans, G Lalloo, F Izatt, L Eeles, R Adlard, J Davidson, R Cole, T Eccles, D Cook, J Hodgson, S Brewer, C Tischkowitz, M Douglas, F Porteous, M Side, L Walker, L Morrison, P Donaldson, A Kennedy, J Foo, C Godwin, AK Schmutzler, RK Wappenschmidt, B Rhiem, K Engel, C Meindl, A Ditsch, N Arnold, N Plendl, HJ Niederacher, D Sutter, C Wang-Gohrke, S Steinemann, D Preisler-Adams, S Kast, K Varon-Mateeva, R Gehrig, A Stoppa-Lyonnet, D Sinilnikova, OM Mazoyer, S Damiola, F Poppe, B Claes, K Piedmonte, M Tucker, K Backes, F Rodriguez, G Brewster, W Wakeley, K Rutherford, T Caldes, T Nevanlinna, H Aittomaki, K Rookus, MA van Os, TAM van der Kolk, L de Lange, JL Meijers-Heijboer, HEJ van der Hout, AH van Asperen, CJ Garcia, EBG Hoogerbrugge, N Collee, JM van Deurzen, CHM van der Luijt, RB Devilee, P Olah, E Lazaro, C Teule, A Menendez, M Jakubowska, A Cybulski, C Gronwald, J Lubinski, J Durda, K Jaworska-Bieniek, K Johannsson, OT Maugard, C Montagna, M Tognazzo, S Teixeira, MR Healey, S Olswold, C Guidugli, L Lindor, N Slager, S Szabo, CI Vijai, J Robson, M Kauff, N Zhang, LY Rau-Murthy, R Fink-Retter, A Singer, CF Rappaport, C Kaulich, DG Pfeiler, G Tea, MK Berger, A Phelan, CM Greene, MH Mai, PL Lejbkowicz, F Andrulis, I Mulligan, AM Glendon, G Toland, AE Bojesen, A Pedersen, IS Sunde, L Thomassen, M Kruse, TA Jensen, UB Friedman, E Laitman, Y Shimon, SP Simard, J Easton, DF Offit, K Couch, FJ Chenevix-Trench, G Antoniou, AC Benitez, J AF Osorio, Ana Milne, Roger L. Kuchenbaecker, Karoline Vaclova, Tereza Pita, Guillermo Alonso, Rosario Peterlongo, Paolo Blanco, Ignacio de la Hoya, Miguel Duran, Mercedes Diez, Orland Ramon y Cajal, Teresa Konstantopoulou, Irene Martinez-Bouzas, Cristina Conejero, Raquel Andres Soucy, Penny McGuffog, Lesley Barrowdale, Daniel Lee, Andrew Arver, Brita Rantala, Johanna Loman, Niklas Ehrencrona, Hans Olopade, Olufunmilayo I. Beattie, Mary S. Domchek, Susan M. Nathanson, Katherine Rebbeck, Timothy R. Arun, Banu K. Karlan, Beth Y. Walsh, Christine Lester, Jenny John, Esther M. Whittemore, Alice S. Daly, Mary B. Southey, Melissa Hopper, John Terry, Mary B. Buys, Saundra S. Janavicius, Ramunas Dorfling, Cecilia M. van Rensburg, Elizabeth J. Steele, Linda Neuhausen, Susan L. Ding, Yuan Chun Hansen, Thomas V. O. Jonson, Lars Ejlertsen, Bent Gerdes, Anne-Marie Infante, Mar Herraez, Belen Moreno, Leticia Thais Weitzel, Jeffrey N. Herzog, Josef Weeman, Kisa Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Scuvera, Giulietta Bonanni, Bernardo Mariette, Frederique Volorio, Sara Viel, Alessandra Varesco, Liliana Papi, Laura Ottini, Laura Tibiletti, Maria Grazia Radice, Paolo Yannoukakos, Drakoulis Garber, Judy Ellis, Steve Frost, Debra Platte, Radka Fineberg, Elena Evans, Gareth Lalloo, Fiona Izatt, Louise Eeles, Ros Adlard, Julian Davidson, Rosemarie Cole, Trevor Eccles, Diana Cook, Jackie Hodgson, Shirley Brewer, Carole Tischkowitz, Marc Douglas, Fiona Porteous, Mary Side, Lucy Walker, Lisa Morrison, Patrick Donaldson, Alan Kennedy, John Foo, Claire Godwin, Andrew K. Schmutzler, Rita Katharina Wappenschmidt, Barbara Rhiem, Kerstin Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Plendl, Hans Joerg Niederacher, Dieter Sutter, Christian Wang-Gohrke, Shan Steinemann, Doris Preisler-Adams, Sabine Kast, Karin Varon-Mateeva, Raymonda Gehrig, Andrea Stoppa-Lyonnet, Dominique Sinilnikova, Olga M. Mazoyer, Sylvie Damiola, Francesca Poppe, Bruce Claes, Kathleen Piedmonte, Marion Tucker, Kathy Backes, Floor Rodriguez, Gustavo Brewster, Wendy Wakeley, Katie Rutherford, Thomas Caldes, Trinidad Nevanlinna, Heli Aittomaki, Kristiina Rookus, Matti A. van Os, Theo A. M. van der Kolk, Lizet de Lange, J. L. Meijers-Heijboer, Hanne E. J. van der Hout, A. H. van Asperen, Christi J. Gomez Garcia, Encarna B. Hoogerbrugge, Nicoline Collee, J. Margriet van Deurzen, Carolien H. M. van der Luijt, Rob B. Devilee, Peter Olah, Edith Lazaro, Conxi Teule, Alex Menendez, Mireia Jakubowska, Anna Cybulski, Cezary Gronwald, Jacek Lubinski, Jan Durda, Katarzyna Jaworska-Bieniek, Katarzyna Johannsson, Oskar Th Maugard, Christine Montagna, Marco Tognazzo, Silvia Teixeira, Manuel R. Healey, Sue Olswold, Curtis Guidugli, Lucia Lindor, Noralane Slager, Susan Szabo, Csilla I. Vijai, Joseph Robson, Mark Kauff, Noah Zhang, Liying Rau-Murthy, Rohini Fink-Retter, Anneliese Singer, Christian F. Rappaport, Christine Kaulich, Daphne Geschwantler Pfeiler, Georg Tea, Muy-Kheng Berger, Andreas Phelan, Catherine M. Greene, Mark H. Mai, Phuong L. Lejbkowicz, Flavio Andrulis, Irene Mulligan, Anna Marie Glendon, Gord Toland, Amanda Ewart Bojesen, Anders Pedersen, Inge Sokilde Sunde, Lone Thomassen, Mads Kruse, Torben A. Jensen, Uffe Birk Friedman, Eitan Laitman, Yael Shimon, Shani Paluch Simard, Jacques Easton, Douglas F. Offit, Kenneth Couch, Fergus J. Chenevix-Trench, Georgia Antoniou, Antonis C. Benitez, Javier CA SWE-BRCA HEBON KConFab Investigators TI DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers SO PLOS GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; BREAST-CANCER; OVARIAN-CANCER; GENETIC MODIFIERS; COMMON VARIANTS; NEIL2; OGG1; INVESTIGATORS; CONSORTIUM; DAMAGE AB Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied. C1 [Osorio, Ana; Vaclova, Tereza; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain. [Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Kuchenbaecker, Karoline; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Ellis, Steve; Frost, Debra; Platte, Radka; Fineberg, Elena; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Pita, Guillermo; Alonso, Rosario; Herraez, Belen; Moreno, Leticia Thais; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Genotyping Unit CeGen, Madrid, Spain. [Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Blanco, Ignacio; Teule, Alex] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain. [de la Hoya, Miguel; Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, IdISSC, Madrid, Spain. [Duran, Mercedes; Infante, Mar] Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain. [Diez, Orland] Univ Hosp Vall dHebron, VHIO, VHIR, Oncogenet Lab, Barcelona, Spain. [Diez, Orland] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Ramon y Cajal, Teresa] Hosp Santa Creu & Sant Pau, Oncol Serv, Barcelona, Spain. [Konstantopoulou, Irene; Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos Aghia Paraskevi Attik, Mol Diagnost Lab IRRP, Athens, Greece. [Martinez-Bouzas, Cristina] Cruces Hosp Barakaldo, Dept Biochem, Mol Genet Lab, Bizkaia, Spain. [Conejero, Raquel Andres] Hosp Clin Lozano Blesa, Med Oncol Serv, Zaragoza, Spain. [Soucy, Penny] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Soucy, Penny] Univ Laval, Quebec City, PQ, Canada. [SWE-BRCA] Lund Univ, Dept Oncol, Lund, Sweden. [Arver, Brita] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Ehrencrona, Hans] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. [Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA USA. [Domchek, Susan M.; Nathanson, Katherine] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Domchek, Susan M.; Nathanson, Katherine] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Karlan, Beth Y.; Walsh, Christine; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA. [Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. [Hopper, John] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Terry, Mary B.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA. [Janavicius, Ramunas] Vilnius Univ Hosp, Santariskiu Clin, Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa. [Steele, Linda; Neuhausen, Susan L.; Ding, Yuan Chun] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Hansen, Thomas V. O.; Jonson, Lars] Univ Copenhagen, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark. [Ejlertsen, Bent] Univ Copenhagen, Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. [Gerdes, Anne-Marie] Univ Copenhagen, Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark. [Weitzel, Jeffrey N.; Herzog, Josef; Weeman, Kisa] City Hope Natl Med Ctr, Clin Canc Genet, Duarte, CA USA. [Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy. [Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy. [Mariette, Frederique; Volorio, Sara] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Mariette, Frederique; Volorio, Sara] Cogentech Canc Genet Test Lab, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Div Expt Oncol 1, Aviano, Italy. [Varesco, Liliana] IST Ist Nazl Ric Cancro, IRCCS AOU San Martino, Dept Epidemiol Prevent & Special Funct, Unit Hereditary Canc, Genoa, Italy. [Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy. [Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. [Tibiletti, Maria Grazia] Osped Circolo Univ Insubria, UO Anat Patol, Varese, Italy. [Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy. [Garber, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Evans, Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Izatt, Louise] Guys Hosp London, South East Thames Reg Genet Serv, London, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, London, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England. [Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England. [Hodgson, Shirley] Univ London, St Georges Hosp, Dept Clin Genet, London, England. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Tischkowitz, Marc] Addenbrookes Hosp, East Anglian Reg Genet Serv, Dept Clin Genet, Cambridge, England. [Douglas, Fiona] Newcastle Upon Tyne Hosp NHS Trust, Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. [Porteous, Mary] Western Gen Hosp, South East Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Side, Lucy] Great Ormond St Hosp Sick Children, North East Thames Reg Genet Serv, London WC1N 3JH, England. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. [Morrison, Patrick] Belfast City Hosp, Northern Ireland Reg Genet Ctr, Belfast BT9 7AD, Antrim, North Ireland. [Donaldson, Alan] South West Reg Genet Serv, Bristol, Avon, England. [Kennedy, John] Univ Dublin Trinity Coll, Acad Unit Clin & Mol Oncol, Dublin 2, Ireland. [Kennedy, John] St James Hosp, Dublin 8, Ireland. [Foo, Claire] Liverpool Womens NHS Fdn Trust, Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin] Univ Hosp Cologne, Ctr Integrated Oncol CIO, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany. [Meindl, Alfons; Ditsch, Nina] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-80290 Munich, Germany. [Arnold, Norbert] Univ Med Ctr Schleswig Holstein, Dept Gynecol & Obstet, Kiel, Germany. [Plendl, Hans Joerg] Univ Med Ctr Schleswig Holstein, Inst Human Genet, Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, Dusseldorf, Germany. [Sutter, Christian] Univ Heidelberg Hosp, Dept Human Genet, Inst Human Genet, Heidelberg, Germany. [Wang-Gohrke, Shan] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Steinemann, Doris] Hannover Med Sch, Inst Cell & Mol Pathol, Hannover, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-48149 Munster, Germany. [Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Obstet & Gynaecol, D-01062 Dresden, Germany. [Varon-Mateeva, Raymonda] Charite, Campus Virchov Klinikum, Inst Human Genet, Berlin, Germany. [Gehrig, Andrea] Univ Wurzburg, Dept Med Genet, Inst Human Genet, Ctr Familial Breast & Ovarian Canc, D-97070 Wurzburg, Germany. [Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumour Biol, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, U830, Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Sinilnikova, Olga M.] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie; Damiola, Francesca] Univ Lyon 1, CNRS UMR5286, INSERM U1052, Ctr Rech Cancerol Lyon, F-69365 Lyon, France. [Poppe, Bruce; Claes, Kathleen] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. [Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Tucker, Kathy] Prince Wales Hosp, Sydney, NSW, Australia. [Backes, Floor] Ohio State Univ, Columbus Canc Council, Columbus, OH 43210 USA. [Rodriguez, Gustavo] NorthShore Univ HealthSyst, Div Gynecol Oncol, Evanston, IL USA. [Brewster, Wendy] NorthShore Univ HealthSyst, Div Gynecol Oncol, Chicago, IL USA. [Wakeley, Katie] Tufts Med Ctr, Boston, MA USA. [Rutherford, Thomas] Yale Univ, Sch Med, New Haven, CT USA. [Nevanlinna, Heli; Aittomaki, Kristiina] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Nevanlinna, Heli; Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [van Os, Theo A. M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [van der Kolk, Lizet] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [de Lange, J. L.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van der Hout, A. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. [Gomez Garcia, Encarna B.] MUMC, Sch Oncol & Dev Biol, Dept Clin Genet, Maastricht, Netherlands. [Gomez Garcia, Encarna B.] MUMC, Sch Oncol & Dev Biol, GROW, Maastricht, Netherlands. [Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands. [van Deurzen, Carolien H. M.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Pathol, Rotterdam, Netherlands. [van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [HEBON] Netherlands Canc Inst, Hereditary Breast & Ovarian Canc Res Grp, Amsterdam, Netherlands. [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. [Lazaro, Conxi; Menendez, Mireia] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain. [Jakubowska, Anna; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Jaworska-Bieniek, Katarzyna] Med Univ Warsaw, Postgrad Sch Mol Med, Warsaw, Poland. [Johannsson, Oskar Th] Univ Iceland, Landspitali Univ Hosp, Dept Oncol, Reykjavik, Iceland. [Johannsson, Oskar Th] Univ Iceland, Fac Med, BMC, Reykjavik, Iceland. [Maugard, Christine] CHRU Nouvel Hop Civil, Hop Univ Strasbourg, Lab Diagnost Genet, Strasbourg, France. [Maugard, Christine] CHRU Nouvel Hop Civil, Hop Univ Strasbourg, Serv Oncohematol, Strasbourg, France. [Montagna, Marco; Tognazzo, Silvia] Veneto Inst Oncol IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal. [Healey, Sue; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet & Computat Biol, Brisbane, Qld 4006, Australia. [KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Melbourne, Vic, Australia. [Olswold, Curtis; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Guidugli, Lucia; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Lindor, Noralane] Mayo Clin, Ctr Individualized Med, Scottsdale, AZ USA. [Slager, Susan] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Szabo, Csilla I.] Univ Delaware, Dept Biol Sci, Ctr Translat Canc Res, Newark, DE USA. [Vijai, Joseph; Robson, Mark; Kauff, Noah; Rau-Murthy, Rohini; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Zhang, Liying] Mem Sloan Kettering Canc Ctr, Diagnost Mol Genet Lab, New York, NY 10021 USA. [Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Berger, Andreas] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Berger, Andreas] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Phelan, Catherine M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Lejbkowicz, Flavio] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel. [Andrulis, Irene] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene] Univ Toronto, Canc Care Ontario, Dept Mol Genet, Toronto, ON, Canada. [Andrulis, Irene] Univ Toronto, Canc Care Ontario, Dept Lab Med, Toronto, ON, Canada. [Andrulis, Irene] Univ Toronto, Canc Care Ontario, Dept Pathobiol, Toronto, ON, Canada. [van der Hout, A. H.; Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Glendon, Gord] Mt Sinai Hosp, Ontario Canc Genet Network Samuel Lunenfeld Res I, Toronto, ON M5G 1X5, Canada. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Dept Internal Med & Mol Virol, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Dept Immunol, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Dept Med Genet, Columbus, OH 43210 USA. [van der Hout, A. H.; Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Clin Biochem, Sect Mol Diagnost, Aalborg, Denmark. [Sunde, Lone; Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Friedman, Eitan; Laitman, Yael; Shimon, Shani Paluch] Sheba Med Ctr, Tel Aviv, Israel. [Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. RP Osorio, A (reprint author), Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. RI Arnold, Norbert/E-3012-2010; Peissel, Bernard/E-8187-2017; Whittemore, Alice/F-9925-2014; Menendez Vila, Mireia/H-9981-2015; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Ditsch, Nina/F-6267-2014; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Osorio, Ana/I-4324-2014; Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; Andrulis, Irene/E-7267-2013; montagna, marco/E-2225-2012; Hoogerbrugge, Nicoline/O-1016-2013; Teixeira, Manuel/E-4885-2011 OI Arnold, Norbert/0000-0003-4523-8808; Sunde, Lone/0000-0002-8479-165X; Kauff, Noah/0000-0001-7242-6156; Joseph, Vijai/0000-0002-7933-151X; Yannoukakos, Drakoulis/0000-0001-7509-3510; Evans, Gareth/0000-0002-8482-5784; Peissel, Bernard/0000-0001-9233-3571; Nevanlinna, Heli/0000-0002-0916-2976; Rappaport-Fuerhauser, Christine/0000-0002-6820-0020; Devilee, Peter/0000-0002-8023-2009; Papi, Laura/0000-0003-4552-9517; Robson, Mark/0000-0002-3109-1692; Barrowdale, Daniel/0000-0003-1661-3939; Eeles, Rosalind/0000-0002-3698-6241; Backes, Floor/0000-0002-9225-6913; Blanco, Ignacio/0000-0002-7414-7481; Menendez Vila, Mireia/0000-0001-8050-0803; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Osorio, Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622; montagna, marco/0000-0002-4929-2150; Teixeira, Manuel/0000-0002-4896-5982 FU Mutua Madrilena Foundation (FMMA); Spanish Association against Cancer [AECC08]; RTICC [06/0020/1060]; European Community [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692, C1287/A11990, C5047/A8385]; National Institutes of Health [CA128978]; Post-Cancer GWAS initiative [1 U19 CA 148537]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR); Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; Swedish Cancer Society; Cancer Association of South Africa (CANSA); NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA125183, R01 CA142996, 1U01CA161032, CA116201]; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; Basser Research Center; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; National Cancer Institute [UM1 CA164920, CA 27469, CA 101165, CA 37517]; Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]; Hereditary Cancer Association (Paveldimo vezio asociacija); LSC [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepaja's municipal council; Morris and Horowitz Families Professorship; NEYE Foundation; City of Hope Clinical Cancer Genetics Community Research Network, National Cancer Institute [RC4A153828]; Office of the Director, National Institutes of Health; Italian Association for Cancer Research (AIRC); FiorGen Foundation for Pharmacogenomics; Associazione CAOS Varese; European Union (European Social Fund - ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA; NIHR; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Intramural Research Program, NCI; RTICC (ISCIII), Spanish Ministry of Economy and Competitivity [RD06/0020/0021]; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI [NWO 184.021.007/CP46]; Hungarian Research Grant KTIA-OTKA [CK-80745]; Polish Foundation of Science; Nordic Cancer Union, Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Ministero dell'Istruzione, dell'Universitae della Ricerca and Ministero della Salute; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; NIH [CA128978]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Sharon Levine Corzine Fund; Niehaus Clinical Cancer Genetics Initiative; Andrew Sabin Family Foundation; Lymphoma Foundation; US National Cancer Institute, NIH; Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), NY; Ohio State University Comprehensive Cancer Center; [FISPI12/00070]; [5U01CA113916]; [R01CA140323] FX The CNIO study was supported by Mutua Madrilena Foundation (FMMA), Spanish Association against Cancer (AECC08), RTICC 06/0020/1060 and FISPI12/00070. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (No. 1 U19 CA 148537 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. SWE-BRCA collaborators are supported by the Swedish Cancer Society. BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to EJvR. UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an ACS Clinical Research Professor. UPENN study is supported by Basser Research Center (SMD, KN, TRR), Breast Cancer Research Foundation (KN), Komen Foundation for the Cure (SMD). The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). BCFR study: This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC is supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012 and Hereditary Cancer Association (Paveldimo vezio asociacija); Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF Nr. 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and Liepaja's municipal council. BRICOH study: NIH R01CA74415 and P30 CA033752. SLN was partially supported by the Morris and Horowitz Families Professorship. CBCS work was supported by the NEYE Foundation. The City of Hope Clinical Cancer Genetics Community Research Network is supported by Award Number RC4A153828 (PI: JNW) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The members of CONSIT TEAM were funded by grants from the Italian Association for Cancer Research (AIRC) to PP, LO and PR; FiorGen Foundation for Pharmacogenomics to LP; Associazione CAOS Varese to MGT and by funds from Italian citizens who allocated the 561000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to SMan and PR.; Demokritos: This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA. Investing in knowledge society through the European Social Fund. We wish to thank Hellenic Cooperative Oncology Group (HeCOG) and the Hellenic Foundation for Cancer Research (HFCR). EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. GE and FLa are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. RE and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. FCCC study: The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, RKS) and by the Center for Molecular Medicine Cologne (CMMC). This study was kindly supported by the German Cancer Aid to RKS (grant no 109076) and by the Center for Molecular Medicine Cologne (CMMC). GEMO study: The study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. GOG study: This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). MHG, PLM and Sharon A. Savage were supported by funding from the Intramural Research Program, NCI. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) CA 27469, CA 37517, and CA 101165. HCSC study was supported by a grant RD06/0020/0021 from RTICC (ISCIII), Spanish Ministry of Economy and Competitivity. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society and the Sigrid Juselius Foundation. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745. IHCC study: KJB is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The ILUH group was supported by the Nordic Cancer Union, Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund.; INHERIT: This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer'' program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. IOVHBOCS study was supported by Ministero dell'Istruzione, dell'Universitae della Ricerca and Ministero della Salute. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. GCT and Amanda B. Spurdle are NHMRC Senior Research Fellows. MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. MSKCC was supported by the Sharon Levine Corzine Fund, Breast Cancer Research Foundation, Niehaus Clinical Cancer Genetics Initiative, Andrew Sabin Family Foundation and Lymphoma Foundation. NCI study: The research of MHG, PLM and Sharon A. Savage was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD. NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. SMC study: This project was partially funded through a grant by the Israel cancer association and the funding for the Israeli Inherited breast cancer consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 8 Z9 8 U1 2 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD APR PY 2014 VL 10 IS 4 AR e1004256 DI 10.1371/journal.pgen.1004256 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AG6AB UT WOS:000335499600026 PM 24698998 ER PT J AU Bouyssou, JMC Manier, S Huynh, D Issa, S Roccaro, AM Ghobrial, IM AF Bouyssou, Juliette M. C. Manier, Salomon Daisy Huynh Issa, Samar Roccaro, Aldo M. Ghobrial, Irene M. TI Regulation of microRNAs in cancer metastasis SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE MicroRNAs; Cancer; Metastasis; EMT; Epigenetics ID EPITHELIAL-MESENCHYMAL TRANSITION; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; HUMAN BREAST-CANCER; GASTRIC-CANCER; COLORECTAL-CANCER; MIR-200 FAMILY; DOWN-REGULATION; E-CADHERIN; HEPATOCELLULAR-CARCINOMA AB Metastasis is a phenomenon of crucial importance in defining prognosis in patients with cancer and is often responsible for cancer-related mortality. It is known that several steps are necessary for clonal cells to disseminate from their primary tumor site and colonize distant tissues, thus originating metastatic lesions. Therefore, investigating the molecular actors regulating this process may provide helpful insights in the development of efficient therapeutic responses. Recent evidences have indicated the role of microRNAs (miRNAs) in modulating the metastatic process in solid tumors. miRNAs are small regulatory non-coding RNAs that bind to specific target mRNAs, leading to translational repression. miRNAs are known to act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both in physiological conditions and during diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an important role in mediating oncogenesis and favoring tumor progression, as a result of their ability to modulate epithelial-to-mesenchymal transition (EMT) and other series of events facilitating the formation of metastasis. The role of miRNAs in cancer development has been widely studied and has helped elucidate events such as the change in expression of oncogenes, tumor-suppressors and cancer-related proteins. This review focuses on the mechanisms underlying the role of miRNAs as part of the metastatic process. (C) 2014 Elsevier B.V. All rights reserved. C1 [Bouyssou, Juliette M. C.; Manier, Salomon; Daisy Huynh; Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bouyssou, Juliette M. C.; Issa, Samar] Ecole Biol Ind, F-95094 Cergy Pontoise, France. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Irene_ghobrial@dfci.harvard.edu FU Leukemia and Lymphoma Society [R01CA154648]; Multiple Myeloma Research Foundation FX Supported in part by R01CA154648, the Leukemia and Lymphoma Society and the Multiple Myeloma Research Foundation. NR 197 TC 72 Z9 77 U1 5 U2 52 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD APR PY 2014 VL 1845 IS 2 BP 255 EP 265 DI 10.1016/j.bbcan2014.02.002 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA AH1IQ UT WOS:000335874200013 PM 24569228 ER PT J AU Bergthold, G Bandopadhayay, P Bi, WL Ramkissoon, L Stiles, C Segal, RA Beroukhim, R Ligon, KL Grill, J Kieran, MW AF Bergthold, Guillaume Bandopadhayay, Pratiti Bi, Wenya Linda Ramkissoon, Lori Stiles, Charles Segal, Rosalind A. Beroukhim, Rameen Ligon, Keith L. Grill, Jacques Kieran, Mark W. TI Pediatric low-grade gliomas: How modern biology reshapes the clinical field SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Pediatric; Low-grade glioma; Genetics; BRAF ID CENTRAL-NERVOUS-SYSTEM; JUVENILE PILOCYTIC ASTROCYTOMAS; OPTIC PATHWAY GLIOMA; CHILDRENS ONCOLOGY GROUP; MIB-1 LABELING INDEX; BRAIN-STEM GLIOMAS; DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; CONFORMAL RADIATION-THERAPY; ONCOGENE-INDUCED SENESCENCE AB Low-grade gliomas represent the most frequent brain tumors arising during childhood. They are characterized by a broad and heterogeneous group of tumors that are currently classified by the WHO according to their morphological appearance. Here we review the clinical features of these tumors, current therapeutic strategies and the recent discovery of genomic alterations characteristic to these tumors. We further explore how these recent biological findings stand to transform the treatment for these tumors and impact the diagnostic criteria for pediatric low-grade gliomas. (C) 2014 Elsevier B.V. All rights reserved. C1 [Bergthold, Guillaume; Bandopadhayay, Pratiti; Bi, Wenya Linda; Stiles, Charles; Segal, Rosalind A.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Grill, Jacques] Univ Paris 11, Dept Cancerol Enfant & Adolescent, Villejuif, France. [Grill, Jacques] Univ Paris 11, CNRS, Unite Mixte Rech 8203, Villejuif, France. [Ramkissoon, Lori; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramkissoon, Lori; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Bandopadhayay, Pratiti; Kieran, Mark W.] Dana Farber Canc Inst, Div Pediat Hematol & Oncol, Boston, MA 02215 USA. [Bandopadhayay, Pratiti; Kieran, Mark W.] Boston Childrens Hosp, Boston, MA USA. [Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Rm D-3154, Boston, MA 02215 USA. EM marlc_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Pediatric Low-Grade Astrocytoma Foundation; Stop&Shop Pediatric Brain Tumor Program; Andrysiak Fund for LGG; Nuovo-Soldati Foundation; Philippe Foundation; Friends of DFCI; Team Jack Foundation; Mill Foundation for Kids; Sontag Foundation; Gray Matters Foundation; NIH [PO1CA142536, PO1NSO47572]; INCA grant [PHRC 2008]; L'Etoile de Martin FX Pediatric Low-Grade Astrocytoma Foundation (GB, PB, RB, LR, RAS, CS and MWK), Stop&Shop Pediatric Brain Tumor Program (PB and MWK), Andrysiak Fund for LGG (MWK), Nuovo-Soldati Foundation (GB), Philippe Foundation (GB), Friends of DFCI (GB and PB),Team Jack Foundation (PB, CS and MWK), the Mill Foundation for Kids (MWK), the Sontag Foundation (RB), Gray Matters Foundation (RB), NIH PO1CA142536 (RAS), NIH PO1NSO47572 (CS), INCA grant PHRC 2008 (JG), L'Etoile de Martin (JG). NR 267 TC 18 Z9 18 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD APR PY 2014 VL 1845 IS 2 BP 294 EP 307 DI 10.1016/j.bbcan.2014.02.004 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA AH1IQ UT WOS:000335874200016 PM 24589977 ER PT J AU Remmers, C Sweet, RA Penzes, P AF Remmers, Christine Sweet, Robert A. Penzes, Peter TI Abnormal kalirin signaling in neuropsychiatric disorders SO BRAIN RESEARCH BULLETIN LA English DT Review DE Schizophrenia; Alzheimer's disease; Mental disorder; Genetic; Glutamatergic; Postmortem ID DENDRITIC SPINE PATHOLOGY; ALZHEIMERS-DISEASE HIPPOCAMPUS; NUCLEOTIDE EXCHANGE FACTOR; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; COGNITIVE IMPAIRMENT; SYNAPTIC PLASTICITY; MENTAL-RETARDATION; FRONTAL-CORTEX; PREFRONTAL CORTEX AB Changes in dendritic spines structure and function play a critical role in a number of physiological processes, including synaptic transmission and plasticity, and are intimately linked to cognitive function. Alterations in dendritic spine morphogenesis occur in a number of neuropsychiatric disorders and likely underlie the cognitive and behavioral changes associated with these disorders. The neuronal guanine nucleotide exchange factor (GEF) kalirin is emerging as a key regulator of structural and functional plasticity at dendritic spines. Moreover, a series of recent studies have genetically and functionally linked kalirin signaling to several disorders, including schizophrenia and Alzheimer's disease. Kalirin signaling may thus represent a disease mechanism and provide a novel therapeutic target. This article is part of a special Issue entitled 'Dendrites and Disease'. (C) 2013 Elsevier Inc. All rights reserved. C1 [Remmers, Christine; Penzes, Peter] Dept Physiol, Chicago, IL 60611 USA. [Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. RP Penzes, P (reprint author), Dept Physiol, 303 E Chicago Ave, Chicago, IL 60611 USA. EM p-penzes@northwestern.edu RI Penzes, Peter/L-3987-2016 OI Penzes, Peter/0000-0001-5449-1640 FU NIH-NIMH [R01MH071316]; Veterans Health Administration [BX000452]; NIH [MH071533, AG005133]; National Center for Research Resources (NCRR); National Center for Advancing Translational Sciences (NCATS); National Institutes of Health (NIH) [8UL1TR000150] FX This work was supported by a grant from NIH-NIMH to P.P. (R01MH071316), by Veterans Health Administration (BX000452) and NIH grants (MH071533 and AG005133) to R.A.S, and by National Center for Research Resources (NCRR) and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) through Grant number 8UL1TR000150 to C.R. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs or, the National Institutes of Health, or the United States Government. NR 112 TC 10 Z9 10 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 EI 1873-2747 J9 BRAIN RES BULL JI Brain Res. Bull. PD APR PY 2014 VL 103 SI SI BP 29 EP 38 DI 10.1016/j.brainresbull.2013.12.006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AH0JV UT WOS:000335806100005 PM 24334022 ER PT J AU Chua, SL Amerson, EH Leslie, KS McCalmont, TH Leboit, PE Martin, JN Bangsberg, D Maurer, TA AF Chua, S. L. Amerson, E. H. Leslie, K. S. McCalmont, T. H. Leboit, P. E. Martin, J. N. Bangsberg, D. Maurer, T. A. TI Factors associated with pruritic papular eruption of human immunodeficiency virus infection in the antiretroviral therapy era SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID T-LYMPHOCYTE ACTIVATION; HIV-INFECTION; MONITOR; BURDEN AB Background Pruritic papular eruption (PPE) of HIV is common in HIV-infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6 months of ART has been proposed as one of several markers of treatment failure. Objectives To determine factors associated with PPE in HIV-infected persons receiving ART. Methods A case-control study nested within a 500-person cohort from a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for >= 15 months and had an itchy papular rash for at least 1 month with microscopic correlation by skin biopsy. Each case was individually matched with two controls for age, sex and ART duration. Results Twenty-five of 45 cases (56%) had microscopic findings consistent with PPE. At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and matched controls had plasma HIV RNA < 400 copies mL(-1) (96% vs. 85%, P = 0.31). The odds of having PPE increased fourfold with every log increase in viral load at ART initiation (P = 0.02) but not at study enrolment. CD4 counts at ART initiation and study enrolment, and CD4 gains and CD8(+) T-cell activation measured 6 and 12 months after ART commencement were not associated with PPE. Study participants who reported daily insect bites had greater odds of being cases [odds ratio (OR) 8.3, P < 0.001] or PPE cases (OR 8.6, P = 0.01). Conclusions Pruritic papular eruption in HIV-infected persons receiving ART for >= 15 months was associated with greater HIV viraemia at ART commencement, independent of CD4 count. Skin biopsies are important to distinguish between PPE and other itchy papular eruptions. C1 [Chua, S. L.] Queen Elizabeth Hosp Birmingham, Dept Dermatol, Birmingham B15 2WB, W Midlands, England. [Amerson, E. H.; Leslie, K. S.; Maurer, T. A.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [McCalmont, T. H.; Leboit, P. E.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Martin, J. N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94140 USA. [Bangsberg, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard,Ctr Global Hlth, Boston, MA USA. [Bangsberg, D.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Chua, SL (reprint author), Queen Elizabeth Hosp Birmingham, Dept Dermatol, Mindelsohn Way, Birmingham B15 2WB, W Midlands, England. EM schua@doctors.org.uk FU National Institutes of Health [R01 MH054907, K24 MH87227, P30 AI027763] FX Uganda AIDS Rural Treatment Outcomes. UARTO is supported by the National Institutes of Health (R01 MH054907, K24 MH87227 and P30 AI027763). S.L.C. was a recipient of the Roger Harman African Travelling Fellowship from the British Association of Dermatologists. NR 24 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2014 VL 170 IS 4 BP 832 EP 839 DI 10.1111/bjd.12721 PG 8 WC Dermatology SC Dermatology GA AE8ND UT WOS:000334257700094 PM 24641299 ER PT J AU Marin, MF Camprodon, JA Dougherty, DD Milad, MR AF Marin, Marie-France Camprodon, Joan A. Dougherty, Darin D. Milad, Mohammed R. TI DEVICE-BASED BRAIN STIMULATION TO AUGMENT FEAR EXTINCTION: IMPLICATIONS FOR PTSD TREATMENT AND BEYOND SO DEPRESSION AND ANXIETY LA English DT Article DE fear learning; extinction retention; exposure therapy; anxiety disorders; TMS; tDCS; VNS; DBS ID POSTTRAUMATIC-STRESS-DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; VENTROMEDIAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; ANTERIOR-CINGULATE-CORTEX; TREATMENT-RESISTANT DEPRESSION; VAGUS NERVE-STIMULATION; CHILDHOOD SEXUAL-ABUSE; CONDITIONED FEAR; HIPPOCAMPAL VOLUME AB Conditioned fear acquisition and extinction paradigms have been widely used both in animals and humans to examine the neurobiology of emotional memory. Studies have also shown that patients suffering from posttraumatic stress disorder (PTSD) exhibit deficient extinction recall along with dysfunctional activation of the fear extinction network, including the ventromedial prefrontal cortex, amygdala, and hippocampus. A great deal of overlap exists between this fear extinction network and brain regions associated with symptom severity in PTSD. This suggests that the neural nodes of fear extinction could be targeted to reduce behavioral deficits that may subsequently translate into symptom improvement. In this article, we discuss potential applications of brain stimulation and neuromodulation methods, which, combined with a mechanistic understanding of the neurobiology of fear extinction, could be used to further our understanding of the pathophysiology of anxiety disorders and develop novel therapeutic tools. To this end, we discuss the following stimulation approaches: deep-brain stimulation, vagus nerve stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation. We propose new translational research avenues that, from a systems neuroscience perspective, aim to expand our understanding of circuit dynamics and fear processing toward the practical development of clinical tools, to be used alone or in combination with behavioral therapies. C1 [Marin, Marie-France; Camprodon, Joan A.; Dougherty, Darin D.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Marin, Marie-France; Camprodon, Joan A.; Dougherty, Darin D.; Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,Off 2614, Boston, MA 02129 USA. EM milad@nmr.mgh.harvard.edu FU Department of Defense [W81XWH-11-2-0079] FX Contract grant sponsor: Department of Defense; Contract grant number: W81XWH-11-2-0079. NR 94 TC 13 Z9 13 U1 5 U2 41 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD APR PY 2014 VL 31 IS 4 BP 269 EP 278 DI 10.1002/da.22252 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AE7JW UT WOS:000334174900001 PM 24634247 ER PT J AU Filippatos, G Teerlink, JR Farmakis, D Cotter, G Davison, BA Felker, GM Greenberg, BH Hua, T Ponikowski, P Severin, T Unemori, E Voors, AA Metra, M AF Filippatos, Gerasimos Teerlink, John R. Farmakis, Dimitrios Cotter, Gad Davison, Beth A. Felker, G. Michael Greenberg, Barry H. Hua, Tsushung Ponikowski, Piotr Severin, Thomas Unemori, Elaine Voors, Adriaan A. Metra, Marco TI Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Serelaxin; Relaxin; Acute heart failure; Heart failure with preserved left ventricular ejection fraction; Diastolic heart failure; Dyspnoea ID TROPONIN ELEVATION; EXERCISE CAPACITY; SYSTOLIC FUNCTION; CLINICAL STATUS; TASK-FORCE; OUTCOMES; LEVOSIMENDAN; EPIDEMIOLOGY; ASSOCIATION; ANTAGONIST AB Aims Serelaxin is effective in relieving dyspnoea and improving multiple outcomes in acute heart failure (AHF). Many AHF patients have preserved ejection fraction (HFpEF). Given the lack of evidence-based therapies in this population, we evaluated the effects of serelaxin according to EF in RELAX-AHF trial. Methods and results RELAX-AHF randomized 1161 AHF patients to 48-h serelaxin (30 mu g/kg/day) or placebo within 16 h from presentation. We compared the effects of serelaxin on efficacy endpoints, safety endpoints, and biomarkers of organ damage between preserved (a parts per thousand yen50%) and reduced (< 50%, HFrEF) EF. HFpEF was present in 26% of patients. Serelaxin induced a similar dyspnoea relief in HFpEF vs. HFrEF patients by visual analogue scale-area under the curve (VAS-AUC) through Day 5 [mean change, 461 (-195, 1117) vs. 397 (10, 783) mm h, P = 0.87], but had possibly different effects on the proportion of patients with moderately or markedly dyspnoea improvement by Likert scale at 6, 12, and 24 h [odds ratio for favourable response, 1.70 (0.98, 2.95) vs. 0.85 (0.62, 1.15), interaction P = 0.030]. No differences were encountered in the effect of serelaxin on short- or long-term outcome between HFpEF and HFrEF patients including cardiovascular death or hospitalization for heart/renal failure through Day 60, cardiovascular death through Day 180, and all-cause death through Day 180. Similar safety and changes in biomarkers (high-sensitivity troponin T, cystatin-C, and alanine/aspartate aminotransferases) were found in both groups. Conclusions In AHF patients with HFpEF compared with those with HFrEF, serelaxin was well tolerated and effective in relieving dyspnoea and had a similar effect on short- and long-term outcome, including survival improvement. C1 [Filippatos, Gerasimos; Farmakis, Dimitrios] Univ Athens, Hosp Attikon, Athens, Greece. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA. [Felker, G. Michael] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. [Greenberg, Barry H.] Univ Calif San Diego, Div Cardiovasc Med, San Diego, CA 92103 USA. [Hua, Tsushung] Novartis Pharmaceut, E Hanover, NJ USA. [Ponikowski, Piotr] Med Univ, Mil Hosp, Dept Heart Dis, Wroclaw, Poland. [Severin, Thomas] Novartis Pharma AG, Basel, Switzerland. [Unemori, Elaine] Corthera Inc, San Carlos, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Brescia, Italy. RP Filippatos, G (reprint author), 28 DoukissisPlakentias, Athens 11523, Greece. EM geros@otenet.gr RI Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449 FU Corthera Inc.; Novartis Pharma AG, Basel, Switzerland FX The RELAX-AHF trial was supported by Corthera Inc., a member of the Novartis group of companies. Steve Winter of Novartis Pharma AG, Basel, Switzerland and Graham Allcock of CircleScience (Tytherington, UK) helped in the preparation of the figures, which was funded by Novartis Pharma AG, Basel, Switzerland. Funding to pay the Open Access publication charges for this article was provided by Novartis Pharma AG. NR 31 TC 39 Z9 39 U1 4 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD APR PY 2014 VL 35 IS 16 BP 1041 EP 1050 DI 10.1093/eurheartj/eht497 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH0MH UT WOS:000335813500012 PM 24316514 ER PT J AU Meder, B Ruhle, F Weis, T Homuth, G Keller, A Franke, J Peil, B Bermejo, JL Frese, K Huge, A Witten, A Vogel, B Haas, J Volker, U Ernst, F Teumer, A Ehlermann, P Zugck, C Friedrichs, F Kroemer, H Dorr, M Hoffmann, W Maisch, B Pankuweit, S Ruppert, V Scheffold, T Kuhl, U Schultheiss, HP Kreutz, R Ertl, G Angermann, C Charron, P Villard, E Gary, F Isnard, R Komajda, M Lutz, M Meitinger, T Sinner, MF Wichmann, HE Krawczak, M Ivandic, B Weichenhan, D Gelbrich, G El-Mokhtari, NE Schreiber, S Felix, SB Hasenfuss, G Pfeufer, A Hubner, N Kaab, S Arbustini, E Rottbauer, W Frey, N Stoll, M Katus, HA AF Meder, Benjamin Ruehle, Frank Weis, Tanja Homuth, Georg Keller, Andreas Franke, Jennifer Peil, Barbara Bermejo, Justo Lorenzo Frese, Karen Huge, Andreas Witten, Anika Vogel, Britta Haas, Jan Voelker, Uwe Ernst, Florian Teumer, Alexander Ehlermann, Philipp Zugck, Christian Friedrichs, Frauke Kroemer, Heyo Doerr, Marcus Hoffmann, Wolfgang Maisch, Bernhard Pankuweit, Sabine Ruppert, Volker Scheffold, Thomas Kuehl, Uwe Schultheiss, Hans-Peter Kreutz, Reinhold Ertl, Georg Angermann, Christiane Charron, Philippe Villard, Eric Gary, Francoise Isnard, Richard Komajda, Michel Lutz, Matthias Meitinger, Thomas Sinner, Moritz F. Wichmann, H. -Erich Krawczak, Michael Ivandic, Boris Weichenhan, Dieter Gelbrich, Goetz El-Mokhtari, Nour-Eddine Schreiber, Stefan Felix, Stephan B. Hasenfuss, Gerd Pfeufer, Arne Huebner, Norbert Kaeaeb, Stefan Arbustini, Eloisa Rottbauer, Wolfgang Frey, Norbert Stoll, Monika Katus, Hugo A. TI A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy SO EUROPEAN HEART JOURNAL LA English DT Article DE Dilated cardiomyopathy; DCM; Genome-wide association study ID CORONARY-ARTERY-DISEASE; HEART-FAILURE; HLA-C; SUSCEPTIBILITY LOCI; MYOCARDITIS; CARDIOLOGY; VARIANTS; SOCIETY; HEALTH; GENE AB Aims Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. Methods and reuslts Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 x 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. Conclusion The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM. C1 [Meder, Benjamin; Weis, Tanja; Franke, Jennifer; Frese, Karen; Vogel, Britta; Haas, Jan; Ehlermann, Philipp; Zugck, Christian; Ivandic, Boris; Rottbauer, Wolfgang; Frey, Norbert; Katus, Hugo A.] Heidelberg Univ, Dept Internal Med 3, D-69120 Heidelberg, Germany. [Meder, Benjamin; Weis, Tanja; Frese, Karen; Haas, Jan; Katus, Hugo A.] DZHK German Ctr Cardiovasc Res, Lubeck, Germany. [Ruehle, Frank; Huge, Andreas; Witten, Anika; Friedrichs, Frauke; Stoll, Monika] Univ Munster, Leibniz Inst Arteriosclerosis Res, D-48149 Munster, Germany. [Homuth, Georg; Voelker, Uwe; Ernst, Florian; Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Keller, Andreas] Univ Saarland, Dept Human Genet, Homburg, Germany. [Peil, Barbara; Bermejo, Justo Lorenzo] Univ Heidelberg Hosp, IMBI, Heidelberg, Germany. [Kroemer, Heyo] Univ Med Greifswald, Dept Pharmacol, Greifswald, Germany. [Doerr, Marcus; Felix, Stephan B.] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany. [Hoffmann, Wolfgang] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Maisch, Bernhard; Pankuweit, Sabine; Ruppert, Volker] Univ Hosp Marburg, Dept Cardiol, Marburg, Germany. [Scheffold, Thomas] Univ Witten Herdecke, Inst Heart & Circulat Res, Dortmund, Germany. [Kuehl, Uwe; Schultheiss, Hans-Peter] Charite, Charite Ctr Cardiovasc Med 11, Dept Cardiol & Pneumonol, D-13353 Berlin, Germany. [Kreutz, Reinhold] Charite, Dept Clin Pharmacol, D-13353 Berlin, Germany. [Ertl, Georg; Angermann, Christiane] Univ & Univ Hosp Wurzburg, Dept Internal Med 1, Wurzburg, Germany. [Ertl, Georg; Angermann, Christiane] Univ & Univ Hosp Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany. [Charron, Philippe; Villard, Eric; Gary, Francoise; Isnard, Richard] Univ Paris 06, Hop La Pitie Salpetriere, AP HP, INSERM UMRS956, Paris, France. [Lutz, Matthias; Frey, Norbert] Univ Kiel, Dept Internal Med, Kiel, Germany. [Meitinger, Thomas] Helmholtz Ctr Munich, Inst Human Genet, Munich, Germany. [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany. [Sinner, Moritz F.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Sinner, Moritz F.] NHLBI, Framingham, MA USA. [Sinner, Moritz F.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Wichmann, H. -Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, Munich, Germany. [Wichmann, H. -Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Krawczak, Michael] Univ Kiel, Inst Med Informat & Stat, Kiel, Germany. [Weichenhan, Dieter] German Canc Res Ctr, Heidelberg, Germany. [Gelbrich, Goetz] Coordinat Ctr Clin Trials Leipzig, Leipzig, Germany. [El-Mokhtari, Nour-Eddine; Schreiber, Stefan] Univ Kiel, Kiel, Germany. [Hasenfuss, Gerd] Univ Gottingen, Dept Cardiol & Pneumol, D-37073 Gottingen, Germany. [Pfeufer, Arne] Tech Univ Munich, Genome Res Ctr Environm Hlth, Inst Human Genet, D-80290 Munich, Germany. [Pfeufer, Arne] Helmholtz Ctr Munich, Munich, Germany. [Huebner, Norbert] Max Delbruck Ctr Mol Med, Berlin, Germany. [Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. [Arbustini, Eloisa] Fdn IRCCS Policlin San Matteo, Ctr Inherited Cardiovasc Dis, Pavia, Italy. [Rottbauer, Wolfgang] Univ Ulm, Dept Internal Med 2, D-89069 Ulm, Germany. RP Katus, HA (reprint author), Heidelberg Univ, Dept Internal Med 3, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM hugo.katus@med.uni-heidelberg.de RI Krawczak, Michael/A-8964-2010; Frey, Norbert/A-9695-2010; Pfeufer, Arne/B-6634-2013; Meitinger, Thomas/O-1318-2015; Katus, Hugo/P-1712-2016; OI Krawczak, Michael/0000-0003-2603-1502; Arbustini, Eloisa/0000-0003-2948-7994; , Andreas/0000-0002-5361-0895 FU Bndesministerium fur Bildung und Forschung' (BMBF) FX This work was supported by grants from the 'Bndesministerium fur Bildung und Forschung' (BMBF): German Center for Cardiovascular Research (GCCR), NGFN II, NGFN- plus, and NGFN- transfer, the medical faculty of the University of Heidelberg, INSIGHT DCM( BMBF & Agence nationale pour la recherche '), the European Union ( FP7 INHERITANCE and BestAgeing), and Deutsche Forschungsgemeinschaft ( SFB TR 19). SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research ( 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg- West Pomerania. Genome- wide data have been supported by the Federal Ministry of Education and Research ( 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg West Pomerania. The Competence Network Heart Failure was funded by the German Federal Ministry of Education and Research ( BMBF, grant number 01GI0205). NR 35 TC 27 Z9 28 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD APR PY 2014 VL 35 IS 16 BP 1069 EP + DI 10.1093/eurheartj/eht251 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH0MH UT WOS:000335813500015 PM 23853074 ER PT J AU Henao, JP Peperzak, KA Lichvar, AB Orebaugh, SL Skledar, SJ Pippi, MA Williams, BA AF Henao, John P. Peperzak, Katherin A. Lichvar, Alicia B. Orebaugh, Steven L. Skledar, Susan J. Pippi, Michael A. Williams, Brian A. TI Extrapyramidal symptoms following administration of oral perphenazine 4 or 8 mg An 11-year retrospective analysis SO EUROPEAN JOURNAL OF ANAESTHESIOLOGY LA English DT Article ID POSTOPERATIVE NAUSEA; PREVENTION; EFFICACY; ONDANSETRON; ANTIEMETICS; DROPERIDOL; MANAGEMENT; SURGERY AB BACKGROUNDPerphenazine is a treatment option in postoperative nausea and vomiting (PONV) prophylaxis. Chronic administration and high dose are known to cause extrapyramidal system (EPS) dysfunction at a frequency of 8%, but the incidence of acute EPS after a single 4 or 8mg dose is unknown.OBJECTIVEA retrospective analysis of patient medication billing data and departmental quality records was performed (January 2001 to 10 July 2012) to identify patients who experienced EPS dysfunction after oral perphenazine.DESIGNA retrospective analysis.SETTINGSurgical outpatients presenting to any one of 10 hospitals in the area of Pittsburgh, Pennsylvania, USA.PATIENTSOverall, 45766 patients received 4 or 8mg of perphenazine before same-day surgery.MAIN OUTCOME MEASURESEPS dysfunction was defined as acute dystonia, akathisia or pseudoparkinsonism. Records were reviewed to determine the likely number of reactions to perphenazine, the nature of these reactions and impact on patient care.RESULTSThere were four likely' cases of EPS dysfunction, and two possible' cases. Five reported events were consistent with akathisia, with the sixth being a dystonic reaction. All six patients had resolution of symptoms, with five receiving intravenous diphenhydramine for treatment. The incidence of EPS dysfunction was 1.3 events per 10000 patients (95% confidence interval (CI) 0.4 to 3.0, based on six events). All patients who experienced reactions pre-operatively were able to proceed to surgery without complications or delay. One patient required unplanned admission and 3-h observation owing to sedation from diphenhydramine. The incidence of EPS dysfunction after oral perphenazine is low. Reactions that did occur were mild and easily treated.CONCLUSIONGiven the infrequent side effects, this single, low dose of perphenazine should be encouraged as a low-risk adjunct to any multimodal PONV prophylaxis regimen, based on the selection criteria described. C1 [Henao, John P.; Peperzak, Katherin A.; Orebaugh, Steven L.] Univ Pittsburgh, Dept Anesthesiol, Med Ctr, Pittsburgh, PA 15261 USA. [Lichvar, Alicia B.; Skledar, Susan J.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15261 USA. [Pippi, Michael A.; Williams, Brian A.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Williams, Brian A.] Vet Affairs Pittsburgh Healthcare Syst, Dept Anesthesiol, Pittsburgh, PA USA. RP Williams, BA (reprint author), Univ Pittsburgh, Dept Anesthesiol, 200 Lothrop St,A-1305, Pittsburgh, PA 15261 USA. EM williamsba@anes.upmc.edu FU National Institutes of Health [UL1 RR024153, UL1TR000005] FX Financial support and sponsorship: assistance with IRB submission and statistical analysis for this project was supported by the National Institutes of Health through Grant Numbers UL1 RR024153 and UL1TR000005. NR 9 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0265-0215 EI 1365-2346 J9 EUR J ANAESTH JI Eur. J. Anaesth. PD APR PY 2014 VL 31 IS 4 BP 231 EP 235 DI 10.1097/EJA.0000000000000048 PG 5 WC Anesthesiology SC Anesthesiology GA AD5AO UT WOS:000333263900008 PM 24503705 ER PT J AU Sander, B de Jong, D Rosenwald, A Xie, WL Balague, O Calaminici, M Carreras, J Gaulard, P Gribben, J Hagenbeek, A Kersten, MJ Molina, TJ Lee, A Montes-Moreno, S Ott, G Raemaekers, J Salles, G Sehn, L Thorns, C Wahlin, BE Gascoyne, RD Weller, E AF Sander, Birgitta de Jong, Daphne Rosenwald, Andreas Xie, Wanling Balague, Olga Calaminici, Maria Carreras, Joaquim Gaulard, Philippe Gribben, John Hagenbeek, Anton Kersten, Marie Jose Molina, Thierry Jo Lee, Abigail Montes-Moreno, Santiago Ott, German Raemaekers, John Salles, Gilles Sehn, Laurie Thorns, Christoph Wahlin, Bjorn E. Gascoyne, Randy D. Weller, Edie TI The reliability of immunohistochemical analysis of the tumor microenvironment in follicular lymphoma: a validation study from the Lunenburg Lymphoma Biomarker Consortium SO HAEMATOLOGICA LA English DT Article ID REGULATORY T-CELLS; INDEPENDENT PREDICTOR; GENE-EXPRESSION; HIGH NUMBERS; CD40 LIGAND; IN-VITRO; SURVIVAL; MACROPHAGES; RITUXIMAB; TRANSFORMATION AB The cellular microenvironment in follicular lymphoma is of biological and clinical importance. Studies on the clinical significance of non-malignant cell populations have generated conflicting results, which may partly be influenced by poor reproducibility in immunohistochemical marker quantification. In this study, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated. The agreement between manual scoring and flow cytometry was moderate for CD3, low for CD4, and moderate to high for CD8, with some laboratories scoring closer to the flow cytometry results. Agreement in manual quantification across the 7 laboratories was low to moderate for CD3, CD4, CD8 and FOXP3 frequencies, moderate for CD21, low for MIB1 and CD68, and high for CD10. Manual scoring of the architectural distribution resulted in moderate agreement for CD3, CD4 and CD8, and low agreement for FOXP3 and CD68. Comparing manual scoring to automated microscopy demonstrated that manual scoring increased the variability in the low and high frequency interval with some laboratories showing a better agreement with automated scores. Manual scoring reliably identified rare architectural patterns of T-cell infiltrates. Automated microscopy analyses for T-cell markers by two different instruments were highly reproducible and provided acceptable agreement with flow cytometry. These validation results provide explanations for the heterogeneous findings on the prognostic value of the microenvironment in follicular lymphoma. We recommend a more objective measurement, such as computer-assisted scoring, in future studies of the prognostic impact of microenvironment in follicular lymphoma patients. C1 [Sander, Birgitta] Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden. [Sander, Birgitta] Karolinska Univ Hosp, Stockholm, Sweden. [de Jong, Daphne; Balague, Olga] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands. [Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, Wurzburg, Germany. [Xie, Wanling; Weller, Edie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Calaminici, Maria; Gribben, John; Lee, Abigail] Univ London, Barts Canc Inst, Ctr Haematooncol, London WC1E 7HU, England. [Carreras, Joaquim] Univ Barcelona, IDIBAPS, Hosp Clin, Hematopathol Sect,Dept Pathol, E-08007 Barcelona, Spain. [Gaulard, Philippe] Univ Paris Est Creteil, Dept Pathol, Paris, France. [Gaulard, Philippe] Univ Paris Est Creteil, INSERM, Hop Henri Mondor, U955, Paris, France. [Hagenbeek, Anton; Kersten, Marie Jose] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands. [Molina, Thierry Jo] Univ Paris 05, Paris, France. [Molina, Thierry Jo] Hop Hotel Dieu, AP HP, Paris, France. [Montes-Moreno, Santiago] Hosp Univ Marques Valdecilla IFIMAV, Dept Pathol, Santander, Spain. [Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Raemaekers, John] Radboud Univ Nijmegen, Med Ctr, Dept Hematol, NL-6525 ED Nijmegen, Netherlands. [Salles, Gilles] Hosp Civils Lyon, Lyon, France. [Salles, Gilles] Univ Lyon 1, CNRS, UMR 5239, F-69365 Lyon, France. [Sehn, Laurie; Gascoyne, Randy D.] Univ British Columbia, British Columbia Canc Agcy, Dept Pathol & Med Oncol, Vancouver, BC V5Z 1M9, Canada. [Thorns, Christoph] Univ Klinikum Schleswig Holstein, Dept Pathol, Kiel, Germany. [Wahlin, Bjorn E.] Karolinska Inst, Div Hematol, Dept Med, Stockholm, Sweden. RP Sander, B (reprint author), Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden. EM birgitta.sander@ki.se RI Thorns, Christoph/E-2945-2010; OI Wahlin, Bjorn/0000-0003-3566-8847; Montes-Moreno, Santiago/0000-0002-3565-8262; Salles, Gilles/0000-0002-9541-8666 FU van Vlissingen Lymphoma Foundation; Genentech/Roche; GlaxoSmithKline; Pfizer Pharma; Teva Pharmaceuticals/Cephalon; Millenium Pharmaceuticals Inc. FX The Lunenburg Lymphoma Biomarker Consortium is a collaboration of 9 international lymphoma collaborative groups, each represented by a clinical investigator and one or more hematopathologists and supported by a team of statisticians. The project has been initiated and is financially supported by the van Vlissingen Lymphoma Foundation. In addition, unrestricted grants were received from Genentech/Roche, GlaxoSmithKline, Pfizer Pharma, Teva Pharmaceuticals/Cephalon and Millenium Pharmaceuticals Inc. EORTC Lymphoma group: Daphne de Jong, John Raemaekers; HOVON: Daphne de Jong, Marie Jose Kersten, Anton Hagenbeek; LYSA (GELA): Philippe Gaulard, Thierry Molina, Josette Briere, Gilles Salles; British Columbia Cancer Center: Randy Gascoyne, Laurie Sehn; ECOG: Randy Gascoyne; DSHBHL (German High Grade non-Hodgkin Lymphoma Group): Christoph Thorns, Andreas Rosenwald, Wolfram Klapper, German Ott, Sylvia Hoeller, Heinz-Wolfram Bernd, Michael Pfreundschuh; NLG: Birgitta Sander, Eva Kimby, Bjorn E. Wahlin; Barts Cancer Institute: Abigail Lee, Andrew Clear, Maria Calaminici, John Gribben, Andrew Lister; Dana-Farber Cancer Institute, Boston, USA: Edie Weller, Wanling Xie; Independent pathology advisor: Elias Campo, Barcelona, Spain. NR 44 TC 19 Z9 19 U1 1 U2 8 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD APR PY 2014 VL 99 IS 4 BP 715 EP 725 DI 10.3324/haematol.2013.095257 PG 11 WC Hematology SC Hematology GA AH6QQ UT WOS:000336256100023 PM 24510338 ER PT J AU Kohrt, BA Rasmussen, A Kaiser, BN Haroz, EE Maharjan, SM Mutamba, BB de Jong, JTVM Hinton, DE AF Kohrt, Brandon A. Rasmussen, Andrew Kaiser, Bonnie N. Haroz, Emily E. Maharjan, Sujen M. Mutamba, Byamah B. de Jong, Joop T. V. M. Hinton, Devon E. TI Cultural concepts of distress and psychiatric disorders: literature review and research recommendations for global mental health epidemiology SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Review DE Culture; developing countries; epidemiologic methods; global mental health; mental disorders; meta-analysis ID ATAQUES-DE-NERVIOS; POSTTRAUMATIC-STRESS-DISORDER; TREATMENT-RESISTANT PTSD; BLOOD-PRESSURE RESPONSE; MIDDLE-INCOME COUNTRIES; PUERTO-RICAN CHILDREN; BRAIN PAG SYNDROME; CAMBODIAN REFUGEES; DHAT-SYNDROME; PANIC-ATTACKS AB Background Burgeoning global mental health endeavors have renewed debates about cultural applicability of psychiatric categories. This study's goal is to review strengths and limitations of literature comparing psychiatric categories with cultural concepts of distress (CCD) such as cultural syndromes, culture-bound syndromes, and idioms of distress. Methods The Systematic Assessment of Quality in Observational Research (SAQOR) was adapted based on cultural psychiatry principles to develop a Cultural Psychiatry Epidemiology version (SAQOR-CPE), which was used to rate quality of quantitative studies comparing CCD and psychiatric categories. A meta-analysis was performed for each psychiatric category. Results Forty-five studies met inclusion criteria, with 18 782 unique participants. Primary objectives of the studies included comparing CCD and psychiatric disorders (51%), assessing risk factors for CCD (18%) and instrument validation (16%). Only 27% of studies met SAQOR-CPE criteria for medium quality, with the remainder low or very low quality. Only 29% of studies employed representative samples, 53% used validated outcome measures, 44% included function assessments and 44% controlled for confounding. Meta-analyses for anxiety, depression, PTSD and somatization revealed high heterogeneity (I-2 > 75%). Only general psychological distress had low heterogeneity (I-2 = 8%) with a summary effect odds ratio of 5.39 (95% CI 4.71-6.17). Associations between CCD and psychiatric disorders were influenced by methodological issues, such as validation designs (beta = 16.27, 95%CI 12.75-19.79) and use of CCD multi-item checklists (beta = 6.10, 95%CI 1.89-10.31). Higher quality studies demonstrated weaker associations of CCD and psychiatric disorders. Conclusions Cultural concepts of distress are not inherently unamenable to epidemiological study. However, poor study quality impedes conceptual advancement and service application. With improved study design and reporting using guidelines such as the SAQOR-CPE, CCD research can enhance detection of mental health problems, reduce cultural biases in diagnostic criteria and increase cultural salience of intervention trial outcomes. C1 [Kohrt, Brandon A.] Duke Global Hlth Inst, Dept Psychiat & Behav Sci, Durham, NC USA. [Rasmussen, Andrew] Fordham Univ, Dept Psychol, New York, NY 10023 USA. [Kaiser, Bonnie N.] Emory Univ, Dept Epidemiol, Dept Anthropol, Atlanta, GA 30322 USA. [Haroz, Emily E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Maharjan, Sujen M.] Tribhuvan Univ, Dept Psychol, Kirtipur, Nepal. [Mutamba, Byamah B.] Butabika Natl Referral Mental & Teaching Hosp, Kampala, Uganda. [de Jong, Joop T. V. M.] Univ Amsterdam, AISSR, NL-1012 WX Amsterdam, Netherlands. [Hinton, Devon E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Boston, MA USA. RP Kohrt, BA (reprint author), Duke Univ, Duke Global Hlth Inst, Trent Hall 213,310 Trent Dr, Durham, NC 27710 USA. EM brandon.kohrt@duke.edu OI Rasmussen, Andrew/0000-0001-9149-4795 FU National Institute of Mental Health [South Asian Hub for Advocacy, Research & Education on Mental Health (SHARE)] [U19 MH095687-01S1]; National Science Foundation Graduate Research Fellowship [0234618] FX This work was supported by the National Institute of Mental Health [U19 MH095687-01S1, South Asian Hub for Advocacy, Research & Education on Mental Health (SHARE), Principal Investigators: Vikram Patel and Atif Rahman] supplement for continuity of research experience during clinical training provided to the first author (BAK). Author BNK is supported by the National Science Foundation Graduate Research Fellowship [Grant No. 0234618]. NR 134 TC 19 Z9 19 U1 8 U2 51 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2014 VL 43 IS 2 BP 365 EP 406 DI 10.1093/ije/dyt227 PG 42 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH1ZD UT WOS:000335919500011 PM 24366490 ER PT J AU Videnovic, A Noble, C Reid, KJ Peng, J Turek, FW Marconi, A Rademaker, AW Simuni, T Zadikoff, C Zee, PC AF Videnovic, Aleksandar Noble, Charleston Reid, Kathryn J. Peng, Jie Turek, Fred W. Marconi, Angelica Rademaker, Alfred W. Simuni, Tanya Zadikoff, Cindy Zee, Phyllis C. TI Circadian Melatonin Rhythm and Excessive Daytime Sleepiness in Parkinson Disease SO JAMA NEUROLOGY LA English DT Article ID HEART-RATE-VARIABILITY; SECRETION PATTERN; SUPRACHIASMATIC NUCLEUS; WAKE CYCLE; DISORDERS; FLUCTUATIONS; PERFORMANCE; HYPOCRETIN; ALZHEIMERS; LEVODOPA AB IMPORTANCE Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. OBJECTIVE To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. INTERVENTIONS Twenty-four hour monitoring of serum melatonin secretion. MAIN OUTCOMES AND MEASURES Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. RESULTS Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score >= 10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. CONCLUSIONS AND RELEVANCE Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD. C1 [Videnovic, Aleksandar] Harvard Univ, Sch Med, Neurol Clin Res Inst, Massachusetts Gen Hosp,Dept Neurol, Boston, MA 02114 USA. [Videnovic, Aleksandar; Noble, Charleston; Reid, Kathryn J.; Marconi, Angelica; Simuni, Tanya; Zadikoff, Cindy; Zee, Phyllis C.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Noble, Charleston] Lund Univ, Dept Phys, S-22362 Lund, Sweden. [Peng, Jie; Rademaker, Alfred W.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Turek, Fred W.] Northwestern Univ, Dept Neurobiol, Chicago, IL 60611 USA. RP Videnovic, A (reprint author), Harvard Univ, Sch Med, Neurol Clin Res Inst, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM avidenovic@mgh.harvard.edu FU National Institute of Neurological and Communicative Disorders and Stroke, NIH [K23 NS072283]; Clinical Scientist Development Award from the American Brain Foundation/Parkinson's Disease Foundation; National Institute on Aging, NIH [5P01AG011412-17]; National Center for Advancing Translational Sciences [8UL1TR000150] FX This study was supported by grant K23 NS072283 from the National Institute of Neurological and Communicative Disorders and Stroke, NIH (Dr Videnovic); by a Clinical Scientist Development Award from the American Brain Foundation/Parkinson's Disease Foundation; by grant 5P01AG011412-17 from the National Institute on Aging, NIH (Dr Turek); and by grant 8UL1TR000150 from the National Center for Advancing Translational Sciences. NR 51 TC 34 Z9 41 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD APR PY 2014 VL 71 IS 4 BP 463 EP 469 DI 10.1001/jamaneurol.2013.6239 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AH2MH UT WOS:000335955100012 PM 24566763 ER PT J AU Felgentreff, K Du, LK Weinacht, KG Dobbs, K Bartish, M Giliani, SC Schlaeger, TM DeVine, A Schambach, A Woodbine, L Davies, GE Baxi, SN van der Burg, M Bleesing, JJ Gennery, AR Manis, JP Pan-Hammarstrom, Q Notarangelo, LD AF Felgentreff, Kerstin Du, Likun Weinacht, Katja G. Dobbs, Kerry Bartish, Margarita Giliani, Silvia C. Schlaeger, Thorsten M. DeVine, Alexander Schambach, Axel Woodbine, Lisa Davies, Graham E. Baxi, Sachin N. van der Burg, Mirjam Bleesing, Jack J. Gennery, Andrew R. Manis, John P. Pan-Hammarstrom, Qiang Notarangelo, Luigi D. TI Differential Role for Dna Ligase 4, Artemis and Dna-Pkcs in the Generation, Dna Damage Response and Myeloid Differentiation of Human Ips Cells SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Felgentreff, Kerstin; Dobbs, Kerry; Baxi, Sachin N.; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Felgentreff, Kerstin; Weinacht, Katja G.; Notarangelo, Luigi D.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Du, Likun; Bartish, Margarita; Pan-Hammarstrom, Qiang] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Div Clin Immunol & Transfus Med,Dept Lab Med, Stockholm, Sweden. [Weinacht, Katja G.; Schlaeger, Thorsten M.; DeVine, Alexander] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. [Weinacht, Katja G.; Schlaeger, Thorsten M.; DeVine, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dobbs, Kerry] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Giliani, Silvia C.] Univ Brescia, Pediat Clin, A Nocivelli Inst Mol Med, Brescia, Italy. [Giliani, Silvia C.] Spedali Civil Brescia, Dept Pathol, Genet Sect, I-25125 Brescia, Italy. [Schambach, Axel] Hannover Med Sch, Inst Expt Hematol, Hannover, Germany. [Woodbine, Lisa] Univ Sussex Falmer Brighton, Sussex Ctr Genome Damage & Stabil, Brighton, E Sussex, England. [Davies, Graham E.] Great Ormond St Hosp Sick Children, Ctr Immunodeficiency, London WC1N 3JH, England. [Davies, Graham E.] Inst Child Hlth, London, England. [van der Burg, Mirjam] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Bleesing, Jack J.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA. [Gennery, Andrew R.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Manis, John P.] Boston Childrens Hosp, Dept Lab Med, Joint Program Transfus Med, 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 SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 352 EP 353 PG 2 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800026 ER PT J AU Walter, JE Rosen, LB Chen, K Lee, YN Tirosh, I Csomos, K Ujhazi, B Al-Herz, W Cowan, MJ Puck, J Bleesing, JJ Malech, H DeRavin, SS Gennery, AR Abraham, RS Butte, MJ Nadeau, KC Sullivan, KE Giliani, S Niehues, T Schuetz, C Kuijpers, T Holland, SM Browne, SK Notarangelo, LD AF Walter, Jolan E. Rosen, Lindsey B. Chen, Karin Lee, Yu Nee Tirosh, Irit Csomos, Krisztian Ujhazi, Boglarka Al-Herz, Waleed Cowan, Morton J. Puck, Jennifer Bleesing, Jack J. Malech, Harry DeRavin, Suk See Gennery, Andrew R. Abraham, Roshini Sarah Butte, Manish J. Nadeau, Kari C. Sullivan, Kathleen E. Giliani, Silvia Niehues, Tim Schuetz, Catharina Kuijpers, Taco Holland, Steven M. Browne, Sarah K. Notarangelo, Luigi D. TI Distinct Anti-Cytokine Autoantibody Profile is Likely Driven by Innate Hyperinflammation Among Patients with Primary Immunodeficiency Secondary To Rag Mutations SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Walter, Jolan E.] Harvard Univ, Sch Med, Boston, MA USA. [Walter, Jolan E.] Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Boston, MA USA. [Walter, Jolan E.; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Rosen, Lindsey B.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Chen, Karin] Univ Utah, Dept Pediat, Div Allergy Immunol & Rheumatol, Salt Lake City, UT USA. [Lee, Yu Nee] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Tirosh, Irit] Boston Childrens Hosp, Boston, MA USA. [Csomos, Krisztian] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. [Ujhazi, Boglarka] Univ Debrecen, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. [Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Kuwait, Kuwait. [Cowan, Morton J.; Puck, Jennifer] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bleesing, Jack J.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA. [Malech, Harry; DeRavin, Suk See] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Gennery, Andrew R.] Newcastle Upon Tyne Hosp, Dept Paediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England. [Abraham, Roshini Sarah] Mayo Clin, Rochester, MN USA. [Butte, Manish J.] Stanford Univ, Dept Pediat, Div Immunol, Stanford, CA 94305 USA. [Nadeau, Kari C.] Stanford Univ, Dept Pediat, Div Immunol, Sch Med, Stanford, CA 94305 USA. [Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Giliani, Silvia] Clin Pediat Azienda Osped Spedali Civili Brescia, Ist Med Mol Angelo Nocivelli, Brescia, Italy. [Niehues, Tim] Acad Hosp, Helios Klinikum Krefeld, Ctr Child Hlth & Adolescence, Dusseldorf, Germany. [Schuetz, Catharina] Univ Hosp, Dept Pediat & Adolescent Med, Ulm, Germany. [Kuijpers, Taco] Emma Childrens Hosp, AMC, Amsterdam, Netherlands. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 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 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 353 EP 354 PG 2 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800030 ER PT J AU Ujhazi, B Csomos, K Fesus, L Notarangelo, LD Korponay-Szabo, IR Walter, J AF Ujhazi, Boglarka Csomos, Krisztian Fesus, Laszlo Notarangelo, Luigi D. Korponay-Szabo, Ilma R. Walter, Jolan TI Detection of Anti-Tissue Transglutaminase Autoantibodies in RAG1 Hypomorph Murine Model of Leaky SCID SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Ujhazi, Boglarka; Csomos, Krisztian] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. [Ujhazi, Boglarka; Fesus, Laszlo] Univ Debrecen, Dept Biochem & Mol Biol, Debrecen, Hungary. [Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Korponay-Szabo, Ilma R.] Heim Pal Childrens Hosp, Budapest, Hungary. [Walter, Jolan] MassGen Hosp Children, Dept Pediat, Div Allergy Immunol, 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 SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 370 EP 370 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800092 ER PT J AU Kuhlen, JL Giallourakis, CP Gibbons, F Hesterberg, P Murali, M Abraham, RS Walter, JE AF Kuhlen, James L., Jr. Giallourakis, Cosmas P. Gibbons, Fiona Hesterberg, Paul Murali, Mandakolathur Abraham, Roshini Sarah Walter, Jolan E. TI A Case of Autoimmunity in Combined Immunodeficiency. Is this Beyond Common Variable Immunodeficiency (CVID)? SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Kuhlen, James L., Jr.; Giallourakis, Cosmas P.; Gibbons, Fiona; Hesterberg, Paul; Murali, Mandakolathur] MGH, Boston, MA USA. Mayo Clin, Rochester, MN USA. [Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 371 EP 371 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800096 ER PT J AU Derfalvi, B Krivan, G Mattyus, I Andorka, C Tulassay, T Veres, G Karpati, S Dobbs, K Csomos, K Massaad, MJ Comeau, AM Thompson, J Notarangelo, LD Walter, J AF Derfalvi, Beata Krivan, Gergely Mattyus, Istvan Andorka, Csilla Tulassay, Tivadar Veres, Gabor Karpati, Sarolta Dobbs, Kerry Csomos, Krisztian Massaad, Michel J. Comeau, Anne Marie Thompson, Jacalyn Notarangelo, Luigi D. Walter, Jolan TI Necrotizing Fistula in Infancy: a Diagnostic Dilemma SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Derfalvi, Beata] Semmelweis Univ, Dept Pediat 2, H-1085 Budapest, Hungary. [Derfalvi, Beata] Dalhousie Univ, Dept Pediat, Div Immunol, IWK Hlth Ctr, Halifax, NS, Canada. [Krivan, Gergely] United St Laszlo & St Istvan Hosp, Budapest, Hungary. [Mattyus, Istvan; Andorka, Csilla; Tulassay, Tivadar; Veres, Gabor] Semmelweis Univ, Dept Pediat 1, H-1085 Budapest, Hungary. [Karpati, Sarolta] Semmelweis Univ, Dept Dermatol & Venereol, H-1085 Budapest, Hungary. [Dobbs, Kerry; Massaad, Michel J.; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA USA. [Csomos, Krisztian] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. [Comeau, Anne Marie; Thompson, Jacalyn] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica Plain, NY USA. [Walter, Jolan] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Div Allergy Immunol, Boston, MA USA. [Walter, Jolan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 389 EP 389 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800162 ER PT J AU Farmer, J Sokol, C Bonilla, F Murali, M Astor, T Walter, JE AF Farmer, Jocelyn Sokol, Caroline Bonilla, Francisco Murali, Mandakolathur Astor, Todd Walter, Jolan E. TI Bilateral Lung Transplantation in a Patient with Atypical Common Variable Immunodeficiency SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Primary Immune Deficiency Diseases North American Conference of the Clinical-Immunology-Society (CIS) CY APR 10-13, 2014 CL Baltimore, MD SP Clin Immunol Soc C1 [Farmer, Jocelyn; Sokol, Caroline; Murali, Mandakolathur; Astor, Todd] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bonilla, Francisco] Childrens Hosp, Boston, MA 02115 USA. [Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2014 VL 34 IS 3 BP 390 EP 390 PG 1 WC Immunology SC Immunology GA AH3SX UT WOS:000336046800165 ER PT J AU Kalapatapu, RK Ho, J Cai, X Vinogradov, S Batki, SL Mohr, DC AF Kalapatapu, Raj K. Ho, Joyce Cai, Xuan Vinogradov, Sophia Batki, Steven L. Mohr, David C. TI Cognitive-Behavioral Therapy in Depressed Primary Care Patients with Co-Occurring Problematic Alcohol Use: Effect of Telephone-Administered vs. Face-to-Face Treatment-A Secondary Analysis SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE alcohol; depressed; face-to-face; primary care; telephone ID RANDOMIZED-CONTROLLED-TRIAL; SUBSTANCE-ABUSE TREATMENT; QUALITY-OF-LIFE; CONTINUING CARE; SMOKING-CESSATION; PROBLEM DRINKING; DUAL DIAGNOSIS; MENTAL-HEALTH; ADDICTION TREATMENT; SELF-MEDICATION AB This secondary analysis of a larger study compared adherence to telephone-administered cognitive-behavioral therapy (T-CBT) vs. face-to-face CBT and depression outcomes in depressed primary care patients with co-occurring problematic alcohol use. To our knowledge, T-CBT has never been directly compared to face-to-face CBT in such a sample of primary care patients. Participants were randomized in a 1: 1 ratio to face-to-face CBT or T-CBT for depression. Participants receiving T-CBT (n = 50) and face-to-face CBT (n = 53) were compared at baseline, end of treatment (week 18), and three-month and six-month follow-ups. Face-to-face CBT and T-CBT groups did not significantly differ in age, sex, ethnicity, marital status, educational level, severity of depression, antidepressant use, and total score on the Alcohol Use Disorders Identification Test. Face-to-face CBT and T-CBT groups were similar on all treatment adherence outcomes and depression outcomes at all time points. T-CBT and face-to-face CBT had similar treatment adherence and efficacy for the treatment of depression in depressed primary care patients with co-occurring problematic alcohol use. When targeting patients who might have difficulties in accessing care, primary care clinicians may consider both types of CBT delivery when treating depression in patients with co-occurring problematic alcohol use. C1 [Kalapatapu, Raj K.; Vinogradov, Sophia; Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Kalapatapu, Raj K.; Vinogradov, Sophia; Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Ho, Joyce; Cai, Xuan; Mohr, David C.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Kalapatapu, RK (reprint author), San Francisco VA Med Ctr, Dept Psychiat, Opioid Replacement Treatment Clin, 4150 Clement St,Mailstop 116F,Bldg 1,Ground Floor, San Francisco, CA 94121 USA. EM kalapatapu.raj.k@gmail.com FU NIDA NIH HHS [K23 DA034883, K23DA034883]; NIMH NIH HHS [R34 MH078922, R01-MH059708, P20 MH090318, R01 MH059708] NR 61 TC 5 Z9 5 U1 4 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0279-1072 EI 2159-9777 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD APR-JUN PY 2014 VL 46 IS 2 BP 85 EP 92 DI 10.1080/02791072.2013.876521 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AH2RL UT WOS:000335968600001 PM 25052784 ER PT J AU Nargiso, JE Kuo, CC Zlotnick, C Johnson, JE AF Nargiso, Jessica E. Kuo, Caroline C. Zlotnick, Caron Johnson, Jennifer E. TI Social Support Network Characteristics of Incarcerated Women with Co-Occurring Major Depressive and Substance Use Disorders SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE depression; dual diagnosis; incarcerated women; social support; substance use disorders; treatment ID MULTIDIMENSIONAL SCALE; PSYCHIATRIC-DISORDERS; GENDER-DIFFERENCES; PSYCHOMETRIC PROPERTIES; DRUG-TREATMENT; ALCOHOL; ABUSE; JAIL; PRISONERS; RELAPSE AB The nature of social support available to incarcerated women is not well-understood, particularly among women at high risk of negative outcomes, including women dually diagnosed with Major Depressive Disorder and a Substance Use Disorder (MDD-SUD). Descriptive statistics and paired-tests were conducted on 60 incarcerated MDD-SUD women receiving in-prison substance use and depression treatments to characterize the women's social networks, including the strength of support, network characteristics, and types of support provided as well as to determine what aspects of social support may be amenable to change during incarceration and post-release. Study results showed that, on average, women perceived they had moderately supportive individuals in their lives, although more than a quarter of the sample could not identify any regular supporters in their network at baseline. During incarceration, women's social networks significantly increased in general supportiveness, and decreased in network size and percentage of substance users in their networks. Participants maintained positive social support gains post-release in most areas while also significantly increasing the size of their support network post-release. Findings suggest that there are aspects of incarcerated MDD-SUD women's social networks that are amenable to change during incarceration and post-release and provide insight into treatment targets for this vulnerable population. C1 [Nargiso, Jessica E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kuo, Caroline C.] Brown Univ, Ctr Alcohol & Addict Studies, Sch Publ Hlth, Providence, RI 02912 USA. [Kuo, Caroline C.] Groote Schuur Hosp Observ, Dept Psychiat & Mental Hlth, Cape Town, South Africa. [Zlotnick, Caron; Johnson, Jennifer E.] Brown Univ, Dept Psychiat & Human Behav, Warren Alpert Med Sch, Providence, RI 02912 USA. [Zlotnick, Caron] Butler Hosp, Providence, RI 02906 USA. RP Nargiso, JE (reprint author), Massachusetts Gen Hosp, 151 Merrimac St,6th Floor, Boston, MA 02114 USA. EM jnargiso@partners.org FU NIDA NIH HHS [K23DA021159, K23 DA021159] NR 55 TC 4 Z9 4 U1 3 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0279-1072 EI 2159-9777 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD APR-JUN PY 2014 VL 46 IS 2 BP 93 EP 105 DI 10.1080/02791072.2014.890766 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AH2RL UT WOS:000335968600002 PM 25052785 ER PT J AU Quigley, KS Barrett, LF AF Quigley, Karen S. Barrett, Lisa Feldman TI Is there consistency and specificity of autonomic changes during emotional episodes? Guidance from the Conceptual Act Theory and psychophysiology SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Autonomic nervous system; Emotion; Psychological construction; Situational response specificity; Individual response specificity; Psychophysiology ID INDIVIDUAL-RESPONSE SPECIFICITY; PSYCHOLOGICAL CONSTRUCTION; PHARMACOLOGICAL BLOCKADES; FUNCTIONAL ARCHITECTURE; STIMULUS-RESPONSE; DISCRETE EMOTIONS; PROACTIVE BRAIN; CARDIAC CONTROL; BASIC EMOTIONS; ANGER AB The consistency and specificity of autonomic nervous system (ANS) responses during emotional episodes remains a topic of debate with relevance for emotional concordance. We present a recent model of how mental states are constructed, the Conceptual Act Theory (CAT), and then review findings from existing meta-analyses and a qualitative review along with studies using pattern classification of multivariate ANS patterns to determine if there is across-study evidence for consistency and specificity of ANS responses during emotional episodes. We conclude that there is thus far minimal evidence for ANS response consistency and specificity across studies. We then review the current understanding of the functional and anatomical features of ANS including its efferent and afferent connections with the central nervous system, which suggests the need to reformulate how we conceptualize ANS response consistency and specificity. We conclude by showing how this reformulation is consistent with the CAT, and how the model suggests when we would and would not expect to see consistency and specificity in ANS responses, and concordance more generally, during emotional episodes. Published by Elsevier B.V. C1 [Quigley, Karen S.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Quigley, Karen S.] Edith Nourse Rogers Bedford Mem VA Hosp, Bedford, MA 01730 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestownl, MA 02129 USA. RP Quigley, KS (reprint author), Northeastern Univ, Dept Psychol, 125 NI, Boston, MA 02115 USA. EM k.quigley@neu.edu FU National Institutes of Health [DP1OD003312] FX This work was supported by a National Institutes of Health Director's Pioneer Award (DP1OD003312) to Lisa Feldman Barrett. NR 94 TC 12 Z9 12 U1 6 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 EI 1873-6246 J9 BIOL PSYCHOL JI Biol. Psychol. PD APR PY 2014 VL 98 BP 82 EP 94 DI 10.1016/j.biopsycho.2013.12.013 PG 13 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA AG6AE UT WOS:000335499900009 PM 24388802 ER PT J AU Ching, SN Brown, EN AF Ching, ShiNung Brown, Emery N. TI Modeling the dynamical effects of anesthesia on brain circuits SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID INDUCED ALPHA-RHYTHM; GENERAL-ANESTHESIA; BURST-SUPPRESSION; GABA(A) RECEPTORS; THALAMOCORTICAL MODEL; SPINDLE OSCILLATIONS; PROPOFOL ANESTHESIA; EEG; CONSCIOUSNESS; ELECTROENCEPHALOGRAM AB General anesthesia is a neurophysiological state that consists of unconsciousness, amnesia, analgesia, and immobility along with maintenance of physiological stability. General anesthesia has been used in the United States for more than 167 years. Now, using systems neuroscience paradigms how anesthetics act in the brain and central nervous system to create the states of general anesthesia is being understood. Propofol is one of the most widely used and the most widely studied anesthetics. When administered for general anesthesia or sedation, the electroencephalogram (EEG) under propofol shows highly structured, rhythmic activity that is strongly associated with changes in the patient's level of arousal. These highly structured oscillations lend themselves readily to mathematical descriptions using dynamical systems models. We review recent model descriptions of the commonly observed EEG patterns associated with propofol: paradoxical excitation, strong frontal alpha oscillations, anteriorization and burst suppression. Our analysis suggests that propofol's actions at GABAergic networks in the cortex, thalamus and brainstem induce profound brain dynamics that are one of the likely mechanisms through which this anesthetic induces altered arousal states from sedation to unconsciousness. Because these dynamical effects are readily observed in the EEG, the mathematical descriptions of how propofol's EEG signatures relate to its mechanisms of action in neural circuits provide anesthesiologists with a neurophysiologically based approach to monitoring the brain states of patients receiving anesthesia care. C1 [Ching, ShiNung] Washington Univ, Dept Elect & Syst Engn, Div Biol & Biomed Sci, St Louis, MO 63130 USA. [Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM enb@neurostat.mit.edu FU National Institutes of Health (NIH) [DP1-OD003646, R01 GM104948-01]; Burroughs-Welcome Fund Careers at the Scientific Interface Award; Massachusetts General Hospital Department of Anesthesia, Critical Care, and Pain Medicine FX Research supported by supported by a National Institutes of Health (NIH) Director's Pioneer Award DP1-OD003646, an NIH Director's Transformative Research Award R01 GM104948-01 (to ENB) and a Burroughs-Welcome Fund Careers at the Scientific Interface Award (to SC). This work was also supported by the Massachusetts General Hospital Department of Anesthesia, Critical Care, and Pain Medicine. NR 62 TC 15 Z9 16 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2014 VL 25 BP 116 EP 122 DI 10.1016/j.conb.2013.12.011 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AG7WF UT WOS:000335628800020 PM 24457211 ER PT J AU Schonbrun, E Malka, R Di Caprio, G Schaak, D Higgins, JM AF Schonbrun, Ethan Malka, Roy Di Caprio, Giuseppe Schaak, Diane Higgins, John M. TI Quantitative Absorption Cytometry for Measuring Red Blood Cell Hemoglobin Mass and Volume SO CYTOMETRY PART A LA English DT Article DE cell volume; hemoglobin mass; red blood cells; quantitative absorption cytometry; microfluidics ID IMAGING FLOW-CYTOMETRY; REFRACTIVE-INDEX; MICROSCOPY; PHASE; DYE; ERYTHROCYTES; EXCLUSION AB We present an optical system, called the quantitative absorption cytometer (QAC), to measure the volume and hemoglobin mass of red blood cells flowing through a microfluidic channel. In contrast to clinical hematology analyzers, where cells are sphered in order for both volume and hemoglobin to be measured accurately, the QAC measures cells in their normal physiological shape. Human red blood cells are suspended in a refractive index-matching absorbing buffer, driven through a microfluidic channel, and imaged using a transmission light microscope onto a color camera. A red and a blue LED illuminate cells and images at each color are used to independently retrieve cell volume and hemoglobin mass. This system shows good agreement with red blood cell indices retrieved by a clinical hematology analyzer and in fact measures a smaller coefficient of variation of hemoglobin concentration. In addition to cell indices, the QAC returns height and mass maps of each measured cell. These quantitative images are valuable for analyzing the detailed morphology of individual cells as well as statistical outliers found in the data. We also measured red blood cells in hypertonic and hypotonic buffers to quantify the correlation between volume and hemoglobin mass under osmotic stress. Because this method is invariant to cell shape, even extremely nonspherical cells in hypertonic buffers can be measured accurately. (c) 2014 International Society for Advancement of Cytometry C1 [Schonbrun, Ethan; Di Caprio, Giuseppe; Schaak, Diane] Harvard Univ, Rowland Inst Harvard, Cambridge, MA 02142 USA. [Malka, Roy; Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Malka, Roy; Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Schonbrun, E (reprint author), Harvard Univ, Rowland Inst, 100 Edwin H Land Blvd, Cambridge, MA 02142 USA. EM schonbrun@rowland.harvard.edu FU NHLBI NIH HHS [U01 HL114476]; NIDDK NIH HHS [DP2 DK098087] NR 26 TC 12 Z9 12 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD APR PY 2014 VL 85 IS 4 BP 332 EP 338 DI 10.1002/cyto.a.22450 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AD9VM UT WOS:000333612700007 PM 24677669 ER PT J AU Kancherla, V Romitti, PA Sun, L Carey, JC Burns, TL Siega-Riz, AM Druschel, CM Lin, AE Olney, RS AF Kancherla, Vijaya Romitti, Paul A. Sun, Lixian Carey, John C. Burns, Trudy L. Siega-Riz, Anna Maria Druschel, Charlotte M. Lin, Angela E. Olney, Richard S. CA Natl Birth Defects Prevention Stud TI Descriptive and risk factor analysis for choanal atresia: The National Birth Defects Prevention Study, 1997-2007 SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Alcohol drinking; Caffeine; Choanal atresia; Cigarette smoking; Diet ID PLASMA ZINC CONCENTRATIONS; MONITORING-SYSTEM PRAMS; NEURAL CREST CELLS; ORAL CLEFTS; CHARGE-SYNDROME; UNITED-STATES; CONGENITAL MALFORMATIONS; PHENOTYPIC SPECTRUM; OROFACIAL CLEFTS; CAFFEINE INTAKE AB Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case-control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997 through 2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. The exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n = 117) and isolated choanal atresia cases (those without additional unrelated major defects; n = 61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CIs) were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR = 1.9; CI = 1.1,3.1), zinc (aOR = 1.7; CI = 1.0,3.1), and niacin (aOR = 1.8; CI = 1.0,3.1), and intake in the lowest quartile for methionine (aOR = 1.6; CI = 1.0,2.6) and vitamin D (aOR = 1.6; CI = 1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR = 2.6; CI = 1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR = 0.4; CI = 0.2,0.9) and fat (aOR = 0.5; 95% CI = 0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR = 2.3; CI = 1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR = 2.5; CI = 1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR = 4.0; CI = 1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Kancherla, Vijaya; Romitti, Paul A.; Sun, Lixian; Burns, Trudy L.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [Carey, John C.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Siega-Riz, Anna Maria] Univ N Carolina, Dept Epidemiol & Nutr, Chapel Hill, NC USA. [Druschel, Charlotte M.] New York State Dept Hlth, Albany, NY USA. [Lin, Angela E.] MassGen Hosp Children, Boston, MA USA. [Olney, Richard S.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. RP Romitti, PA (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, S416 CPHB,145 N Riverside Dr, Iowa City, IA 52242 USA. EM paul-romitti@uiowa.edu FU Centers for Disease Control and Prevention (CDC) [5U01DD000492, 1U01DD001035]; Nutrition Epidemiology Core of the University of North Carolina Clinical Nutrition Research Center [DK56350] FX The authors thank the many study participants and study staff at each site who have contributed to the NBDPS. We also are grateful for the expert administrative assistance provided by Ms. Julee Bormet in the preparation of this manuscript. This work was funded by grants (5U01DD000492 and 1U01DD001035) from the Centers for Disease Control and Prevention (CDC). The CDC was a participating site in the NBDPS and contributed to: study design; data collection, analysis, and interpretation; co-authoring the article, and in the decision to submit the article for publication. Coding of drug information in the National Birth Defects Prevention Study used the Slone Drug Dictionary under license from the Slone Epidemiology Center of Boston University. Nutritional analysis was supported by grant no. DK56350 from the Nutrition Epidemiology Core of the University of North Carolina Clinical Nutrition Research Center. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 69 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 EI 1878-0849 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD APR PY 2014 VL 57 IS 5 BP 220 EP 229 DI 10.1016/j.ejmg.2014.02.010 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AG5GJ UT WOS:000335447200007 PM 24576610 ER PT J AU Noel, SD Abreu, AP Xu, SY Muyide, T Gianetti, E Tusset, C Carroll, J Latronico, AC Seminara, SB Carroll, RS Kaiser, UB AF Noel, Sekoni D. Abreu, Ana Paula Xu, Shuyun Muyide, Titilayo Gianetti, Elena Tusset, Cintia Carroll, Jessica Latronico, Ana Claudia Seminara, Stephanie B. Carroll, Rona S. Kaiser, Ursula B. TI TACR3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients SO FASEB JOURNAL LA English DT Article DE tachykinins; GPCR; hypogonadotropic hypogonadism; neurokinin B ID CALCIUM-SENSING RECEPTOR; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; ACTIVITY-MODIFYING PROTEINS; 3RD INTRACELLULAR LOOP; 1ST EXTRACELLULAR LOOP; NEUROKININ B RECEPTOR; HUMAN SUBSTANCE-P; ARCUATE NUCLEUS; HORMONE SECRETION; QUALITY-CONTROL AB Neurokinin B (NKB) and its G-protein-coupled receptor, NK3R, have been implicated in the neuroendocrine control of GnRH release; however, little is known about the structure-function relationship of this ligand-receptor pair. Moreover, loss-of-function NK3R mutations cause GnRH deficiency in humans. Using missense mutations in NK3R we previously identified in patients with GnRH deficiency, we demonstrate that Y256H and Y315C NK3R mutations in the fifth and sixth transmembrane domains (TM5 and TM6), resulted in reduced whole-cell (79.3 +/- 7.2%) or plasma membrane (67.3 +/- 7.3%) levels, respectively, compared with wild-type (WT) NK3R, with near complete loss of inositol phosphate (IP) signaling, implicating these domains in receptor trafficking, processing, and/or stability. We further demonstrate in a FRET-based assay that R295S NK3R, in the third intracellular loop (IL3), bound NKB but impaired dissociation of G(q)-protein subunits from the receptor compared with WT NK3R, which showed a 10.0 +/- 1.3% reduction in FRET ratios following ligand binding, indicating activation of G(q)-protein signaling. Interestingly, R295S NK3R, identified in the heterozygous state in a GnRH-deficient patient, also interfered with dissociation of G proteins and IP signaling from wild-type NK3R, indicative of dominant-negative effects. Collectively, our data illustrate roles for TM5 and TM6 in NK3R trafficking and ligand binding and for IL3 in NK3R signaling.-Noel, S. D., Abreu, A. P., Xu, S., Muyide, T., Gianetti, E., Tusset, C., Carroll, J., Latronico, A. C., Seminara, S. B., Carroll, R. S., Kaiser, U. B. TACR3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients. C1 [Noel, Sekoni D.; Abreu, Ana Paula; Xu, Shuyun; Muyide, Titilayo; Carroll, Jessica; Carroll, Rona S.; Kaiser, Ursula B.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Noel, Sekoni D.; Abreu, Ana Paula; Xu, Shuyun; Muyide, Titilayo; Carroll, Jessica; Carroll, Rona S.; Kaiser, Ursula B.] Harvard Univ, Sch Med, Boston, MA USA. [Abreu, Ana Paula; Tusset, Cintia; Latronico, Ana Claudia] Univ Sao Paulo, Sch Med, Teaching Hosp, Dev Endocrinol Unit,Lab Hormones & Mol Genet, Sao Paulo, Brazil. [Gianetti, Elena; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Kaiser, UB (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM ukaiser@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH [U54 HD028138]; Ruth L. Kirschstein National Research Service Postdoctoral Award [T32 DK007529-25]; NIH Fellowship [F05 HD072773-01]; [R01 HD019938]; [R01 HD019938-21S] FX The authors thank Dr. John Gill and Dr. Ann-Marie Zavacki for helpful discussions. The authors also thank Drs. Bertil Hille (University of Washington School of Medicine, Seattle, WA, USA), Narasimhan Gautam (Washington University School of Medicine in St. Louis, St. Louis, MO, USA), Stephen Ikeda [National Institute on Alcohol Abuse and Alcoholism, Division of Clinical and Biological Research, U. S. National Institutes of Health (NIH), Bethesda, MD, USA] and Moritz Buneman (Philipps-Universtitaet Marburg, Marburg, Germany) for providing DNA constructs. This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, through cooperative agreement U54 HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (to U. B. K. and S. B. S.), by R01 HD019938 (to U. B. K.), by a T32 DK007529-25 Ruth L. Kirschstein National Research Service Postdoctoral Award (to S.D.N.), by a F05 HD072773-01 NIH Fellowship (to A. P. A.), and by R01 HD019938-21S1 (to J.C.). Author contributions: S.D.N., R. S. C., and U. B. K. designed the study; S.D.N, A. P. A, S. X, T. M., E. G., and J.C. performed experiments; S.D.N. collected and analyzed data; E. G., C. T., A. C. L., S. B. S., R. S. C., and U. B. K. provided materials and reagents; S.D.N. and U. B. K. wrote the manuscript; A. C. L., S. B. S., R. S. C., and U. B. K. gave technical support and conceptual advice. The authors declare no conflicts of interest. NR 87 TC 4 Z9 4 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2014 VL 28 IS 4 BP 1924 EP 1937 DI 10.1096/fj.13-240630 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AG3UC UT WOS:000335344300036 PM 24376026 ER PT J AU Gros, DF Sarver, NW AF Gros, Daniel F. Sarver, Nina Wong TI An investigation of the psychometric properties of the Social Thoughts and Beliefs Scale (STABS) and structure of cognitive symptoms in participants with social anxiety disorder and healthy controls SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Social Thoughts and Beliefs Scale; STABS; Social phobia; Social anxiety disorder; Cognitive; Validity; Reliability ID RATING-SCALE; PHOBIA; THERAPY; MODEL; DEPRESSION; INVENTORY AB Despite the recent increase of measures developed to assess the cognitive symptoms of social anxiety disorder (SOC), their validation is still largely preliminary. Thus, the present studies sought to replicate and extend the psychometric evaluation of the Social Thoughts and Beliefs Scale (STABS). Study 1 involved both participants with SOC (n=206) and healthy controls (n=222) that completed the STABS and other related measures of anxiety. In Study 2, participants with SOC (n=66) completed exposure-based psychotherapy for SOC with the STABS used to track symptom changes. Together, the two studies provided additional support for the validity and reliability of the STABS as a measure of the cognitive symptoms of SOC. However, contrary to previous research with two subscales, a single total scale was suggested as the best interpretation of the STABS, as well as the possible general presentation of the cognitive symptoms of SOC. Published by Elsevier Ltd. C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv, Charleston, SC 29401 USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Sarver, Nina Wong] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU CSRD VA [IK2 CX000845]; NIMH NIH HHS [R01 MH062547, R01MH062547] NR 38 TC 4 Z9 4 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2014 VL 28 IS 3 BP 283 EP 290 DI 10.1016/j.janxdis.2014.01.004 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AG7RO UT WOS:000335616000001 PM 24607834 ER PT J AU Klann, JG Szolovits, P Downs, SM Schadow, G AF Klann, Jeffrey G. Szolovits, Peter Downs, Stephen M. Schadow, Gunther TI Decision support from local data: Creating adaptive order menus from past clinician behavior SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Clinical Decision Support; Data mining; Bayesian analysis ID ELECTRONIC HEALTH RECORDS; SYSTEMS; PHYSICIANS; CARE; SAFETY; ENTRY; CURVE AB Objective: Reducing care variability through guidelines has significantly benefited patients. Nonetheless, guideline-based Clinical Decision Support (CDS) systems are not widely implemented or used, are frequently out-of-date, and cannot address complex care for which guidelines do not exist. Here, we develop and evaluate a complementary approach - using Bayesian Network (BN) learning to generate adaptive, context-specific treatment menus based on local order-entry data. These menus can be used as a draft for expert review, in order to minimize development time for local decision support content. This is in keeping with the vision outlined in the US Health Information Technology Strategic Plan, which describes a healthcare system that learns from itself. Materials and methods: We used the Greedy Equivalence Search algorithm to learn four 50-node domain-specific BNs from 11,344 encounters: abdominal pain in the emergency department, inpatient pregnancy, hypertension in the Urgent Visit Clinic, and altered mental state in the intensive care unit. We developed a system to produce situation-specific, rank-ordered treatment menus from these networks. We evaluated this system with a hospital-simulation methodology and computed Area Under the Receiver-Operator Curve (AUC) and average menu position at time of selection. We also compared this system with a similar association-rule-mining approach. Results: A short order menu on average contained the next order (weighted average length 3.91-5.83 items). Overall predictive ability was good: average AUC above 0.9 for 25% of order types and overall average AUC .714-.844 (depending on domain). However, AUC had high variance (.50-.99). Higher AUC correlated with tighter clusters and more connections in the graphs, indicating importance of appropriate contextual data. Comparison with an Association Rule Mining approach showed similar performance for only the most common orders with dramatic divergence as orders are less frequent. Discussion and conclusion: This study demonstrates that local clinical knowledge can be extracted from treatment data for decision support. This approach is appealing because: it reflects local standards; it uses data already being captured; and it produces human-readable treatment-diagnosis networks that could be curated by a human expert to reduce workload in developing localized CDS content. The BN methodology captured transitive associations and co-varying relationships, which existing approaches do not. It also performs better as orders become less frequent and require more context. This system is a step forward in harnessing local, empirical data to enhance decision support. (C) 2013 Elsevier Inc. All rights reserved. C1 [Klann, Jeffrey G.] Massachusetts Gen Hosp, Comp Sci Lab, Constitut Ctr 1, Boston, MA 02129 USA. [Klann, Jeffrey G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Szolovits, Peter] MIT, Comp Sci & Artificial Intelligence Lab, Stata Ctr, Cambridge, MA 02139 USA. [Downs, Stephen M.] Indiana Univ Sch Med, Childrens Hlth Serv Res, Indianapolis, IN 46202 USA. [Klann, Jeffrey G.; Downs, Stephen M.; Schadow, Gunther] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. RP Klann, JG (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Constitut Ctr 1, Suite 200, Boston, MA 02129 USA. EM jeff.Klann@mgh.harvard.edu OI Szolovits, Peter/0000-0001-8411-6403 FU National Library of Medicine [5T15 LM007117-14] FX Thanks to Jeff Warvel for providing both data and expertise regarding the county-hospital order-entry system; and to Siu Hui for her insights into statistics and evaluation approaches. This work was performed at the Regenstrief Institute, Indianapolis, IN and at the Massachusetts General Hospital Laboratory for Computer Science, Boston, MA. This work was supported in part by Grant 5T15 LM007117-14 from the National Library of Medicine. NR 42 TC 4 Z9 5 U1 6 U2 24 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD APR PY 2014 VL 48 BP 84 EP 93 DI 10.1016/j.jbi.2013.12.005 PG 10 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA AG4ZP UT WOS:000335429200009 PM 24355978 ER PT J AU Bardach, NS Coker, TR Zima, BT Murphy, JM Knapp, P Richardson, LP Edwall, G Mangione-Smith, R AF Bardach, Naomi S. Coker, Tumaini R. Zima, Bonnie T. Murphy, J. Michael Knapp, Penelope Richardson, Laura P. Edwall, Glenace Mangione-Smith, Rita TI Common and Costly Hospitalizations for Pediatric Mental Health Disorders SO PEDIATRICS LA English DT Article DE pediatric hospitalization; child mental health; depression; bipolar disorder; psychosis; costs ID DEPRESSIVE SYMPTOMS; CHILDREN; CARE; ADOLESCENTS; READMISSION; DISPARITIES; PREVALENCE; CALIFORNIA; HOSPITALS; DISEASE AB BACKGROUND AND OBJECTIVES:Inpatient pediatric mental health is a priority topic for national quality measurement and improvement, but nationally representative data on the patients admitted or their diagnoses are lacking. Our objectives were: to describe pediatric mental health hospitalizations at general medical facilities admitting children nationally; to assess which pediatric mental health diagnoses are frequent and costly at these hospitals; and to examine whether the most frequent diagnoses are similar to those at free-standing children's hospitals.METHODS:We examined all discharges in 2009 for patients aged 3 to 20 years in the nationally representative Kids' Inpatient Database (KID) and in the Pediatric Health Information System (free-standing children's hospitals). Main outcomes were frequency of International Classification of Diseases, Ninth Revision, Clinical Modification-defined mental health diagnostic groupings (primary and nonprimary diagnosis) and, using KID, resource utilization (defined by diagnostic grouping aggregate annual charges).RESULTS:Nearly 10% of pediatric hospitalizations nationally were for a primary mental health diagnosis, compared with 3% of hospitalizations at free-standing children's hospitals. Predictors of hospitalizations for a primary mental health problem were older age, male gender, white race, and insurance type. Nationally, the most frequent and costly primary mental health diagnoses were depression (44.1% of all mental health admissions; $1.33 billion), bipolar disorder (18.1%; $702 million), and psychosis (12.1%; $540 million).CONCLUSIONS:We identified the child mental health inpatient diagnoses with the highest frequency and highest costs as depression, bipolar disorder, and psychosis, with substance abuse an important comorbid diagnosis. These diagnoses can be used as priority conditions for pediatric mental health inpatient quality measurement. C1 [Bardach, Naomi S.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Coker, Tumaini R.] Univ Calif Los Angeles, Childrens Discovery & Innovat Inst, Los Angeles, CA USA. [Coker, Tumaini R.] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. [Coker, Tumaini R.] RAND Corp, Santa Monica, CA USA. [Zima, Bonnie T.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Murphy, J. Michael] Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. [Murphy, J. Michael] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Knapp, Penelope] Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. [Richardson, Laura P.; Mangione-Smith, Rita] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Richardson, Laura P.; Mangione-Smith, Rita] Seattle Childrens Res Inst, Ctr Child Hlth Behav & Dev, Seattle, WA USA. [Edwall, Glenace] Minnesota State Hlth Access Data Assistance Ctr, Minneapolis, MN USA. RP Bardach, NS (reprint author), 3333 Calif St,Suite 265, San Francisco, CA 94118 USA. EM bardachn@peds.ucsf.edu OI Bardach, Naomi/0000-0002-5178-0719 FU AHRQ HHS [U18 HS020506, U18 HS020506-03]; NICHD NIH HHS [K23 HD065836, K23HD065836] NR 36 TC 13 Z9 13 U1 2 U2 11 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2014 VL 133 IS 4 BP 602 EP 609 DI 10.1542/peds.2013-3165 PG 8 WC Pediatrics SC Pediatrics GA AG3TU UT WOS:000335343500006 PM 24639270 ER PT J AU Wendt, JM Cohen, JA Mu, Y Dumyati, GK Dunn, JR Holzbauer, SM Winston, LG Johnston, HL Meek, JI Farley, MM Wilson, LE Phipps, EC Beldavs, ZG Gerding, DN McDonald, LC Gould, CV Lessa, FC AF Wendt, Joyanna M. Cohen, Jessica A. Mu, Yi Dumyati, Ghinwa K. Dunn, John R. Holzbauer, Stacy M. Winston, Lisa G. Johnston, Helen L. Meek, James I. Farley, Monica M. Wilson, Lucy E. Phipps, Erin C. Beldavs, Zintars G. Gerding, Dale N. McDonald, L. Clifford Gould, Carolyn V. Lessa, Fernanda C. TI Clostridium difficile Infection Among Children Across Diverse US Geographic Locations SO PEDIATRICS LA English DT Article DE Clostridium difficile; pediatric; community-associated; antimicrobial stewardship ID PROTON PUMP INHIBITORS; RETAIL MEAT; INFANTS; RISK; DISEASE; COLONIZATION; EPIDEMIOLOGY; COMMUNITY; INPATIENTS; DIARRHEA AB OBJECTIVE: Little is known about the epidemiology of Clostridium difficile infection (CDI) among children, particularly children <= 3 years of age in whom colonization is common but pathogenicity uncertain. We sought to describe pediatric CDI incidence, clinical presentation, and outcomes across age groups. METHODS: Data from an active population-and laboratory-based CDI surveillance in 10 US geographic areas during 2010-2011 were used to identify cases (ie, residents with C difficile-positive stool without a positive test in the previous 8 weeks). Community-associated (CA) cases had stool collected as outpatients or <= 3 days after hospital admission and no overnight health care facility stay in the previous 12 weeks. A convenience sample of CA cases were interviewed. Demographic, exposure, and clinical data for cases aged 1 to 17 years were compared across 4 age groups: 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17 years. RESULTS: Of 944 pediatric CDI cases identified, 71% were CA. CDI incidence per 100 000 children was highest among 1-year-old (66.3) and white (23.9) cases. The proportion of cases with documented diarrhea (72%) or severe disease (8%) was similar across age groups; no cases died. Among the 84 cases interviewed who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks. CONCLUSIONS: Similar disease severity across age groups suggests an etiologic role for C difficile in the high rates of CDI observed in younger children. Prevention efforts to reduce unnecessary antimicrobial use among young children in outpatient settings should be prioritized. C1 [Wendt, Joyanna M.; Cohen, Jessica A.; Mu, Yi; McDonald, L. Clifford; Gould, Carolyn V.; Lessa, Fernanda C.] CDC, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Wendt, Joyanna M.] CDC, Epidem Intelligence Serv, Off Surveillance Epidemiol & Lab Serv, Atlanta, GA 30333 USA. [Holzbauer, Stacy M.] CDC, Off Publ Hlth Preparedness & Response, Career Epidemiol Field Off Program, Atlanta, GA 30333 USA. [Cohen, Jessica A.] Atlanta Res & Educ Fdn, Atlanta, GA USA. [Dumyati, Ghinwa K.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. [Dunn, John R.] Tennessee Dept Hlth, Nashville, TN USA. [Holzbauer, Stacy M.] Minnesota Dept Hlth, Dept Med, St Paul, MN USA. [Winston, Lisa G.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Johnston, Helen L.] Colorado Dept Publ Hlth & Environm, Denver, CO USA. [Meek, James I.] Yale Univ, Sch Publ Hlth, Connecticut Emerging Infect Program, New Haven, CT USA. [Farley, Monica M.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Farley, Monica M.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Wilson, Lucy E.] Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA. [Phipps, Erin C.] Univ New Mexico, Emerging Infect Program, Albuquerque, NM 87131 USA. [Beldavs, Zintars G.] Oregon Hlth Author, Publ Hlth Div, Portland, OR USA. [Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Dept Med, Maywood, IL USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Lessa, FC (reprint author), 1600 Clifton Rd,MS A-24, Atlanta, GA 30333 USA. EM flessa@cdc.gov FU Centers for Disease Control and Prevention FX This work was funded by the Centers for Disease Control and Prevention. No external funding was used for this study. NR 33 TC 29 Z9 31 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2014 VL 133 IS 4 BP 651 EP 658 DI 10.1542/peds.2013-3049 PG 8 WC Pediatrics SC Pediatrics GA AG3TU UT WOS:000335343500012 PM 24590748 ER PT J AU Drehmer, JE Ossip, DJ Nabi-Burza, E Rigotti, NA Hipple, B Woo, H Chang, YC Winickoff, JP AF Drehmer, Jeremy E. Ossip, Deborah J. Nabi-Burza, Emara Rigotti, Nancy A. Hipple, Bethany Woo, Heide Chang, Yuchiao Winickoff, Jonathan P. TI Thirdhand Smoke Beliefs of Parents SO PEDIATRICS LA English DT Article DE smoking; tobacco; thirdhand smoke; pediatrics; family practice; parent; smoking cessation; secondhand smoke; environmental tobacco smoke; tobacco control ID TOBACCO-SMOKE; NICOTINE; MODEL; CARCINOGEN; CESSATION; SURFACES; EXPOSURE; OZONE; BANS AB OBJECTIVE:To determine if the belief that thirdhand smoke is harmful to children is associated with smoking parents' attitudes, home or car smoking policies, and quitting behaviors.METHODS:Data from a national randomized controlled trial, Clinical Effort Against Secondhand Smoke Exposure, assessed thirdhand smoke beliefs of 1947 smoking parents in an exit survey after a pediatric office visit in 10 intervention and 10 control practices. Twelve-month follow-up data were collected from 1355 parents. Multivariable logistic regression determined whether belief that thirdhand smoke harms the health of children is independently associated with parental behaviors and attitudes 12 months later. A (2) test assessed whether parents who disagreed that thirdhand smoke is harmful were more likely to make a quit attempt if they later believed that thirdhand smoke is harmful.RESULTS:Belief at the exit survey that thirdhand smoke is harmful was independently associated with having a strictly enforced smoke-free home policy (adjusted odds ratio: 2.05; 95% CI: 1.37-3.05) and car policy (adjusted odds ratio: 1.69; 95% CI: 1.04-2.74) at the 12-month follow-up. A significantly higher percentage (71% vs 50%) of parents who did not hold the thirdhand smoke harm belief at baseline made at least 1 quit attempt if they agreed that thirdhand smoke is harmful at the 12-month follow-up (P = .02).CONCLUSIONS:Thirdhand smoke harm belief was associated with a strictly enforced smoke-free home and car and attempts to quit smoking. Sensitizing parents to thirdhand smoke risk could facilitate beneficial tobacco control outcomes. C1 [Drehmer, Jeremy E.; Nabi-Burza, Emara; Hipple, Bethany; Winickoff, Jonathan P.] Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Drehmer, Jeremy E.; Nabi-Burza, Emara; Rigotti, Nancy A.; Hipple, Bethany; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Ossip, Deborah J.] Univ Rochester, Med Ctr, Dept Publ Hlth Sci, Rochester, NY 14642 USA. [Rigotti, Nancy A.; Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Woo, Heide] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Winickoff, Jonathan P.] Amer Acad Pediat, AAP Richmond Ctr Excellence, Elk Grove Village, IL USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor,Suite 1542A, Boston, MA 02114 USA. EM jwinickoff@mgh.harvard.edu OI Drehmer, Jeremy/0000-0002-5022-5836 FU National Institutes of Health NCI [R01-CA127127]; National Institute on Drug Abuse; Agency for Healthcare Research and Quality; Flight Attendant Medical Research Institute; Pediatric Research in Office Settings (PROS) Network; Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau [HRSA 5-UA6-10-001]; American Academy of Pediatrics FX Supported by the National Institutes of Health NCI grant R01-CA127127 (to Dr Winickoff), the National Institute on Drug Abuse, and the Agency for Healthcare Research and Quality. This study was also partially supported by a grant from the Flight Attendant Medical Research Institute to the AAP Julius B. Richmond Center and the Pediatric Research in Office Settings (PROS) Network, which receives core funding from the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau (HRSA 5-UA6-10-001) and the American Academy of Pediatrics. No funding agency had any role in the design, analysis, or interpretation of the data. Funded by the National Institutes of Health (NIH). NR 24 TC 7 Z9 7 U1 4 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2014 VL 133 IS 4 BP E850 EP E856 DI 10.1542/peds.2013-3392 PG 7 WC Pediatrics SC Pediatrics GA AG3TU UT WOS:000335343500032 PM 24590745 ER PT J AU Cooper, DC Trivedi, RB Nelson, KM Reiber, GE Eugenio, EC Beaver, KA Fan, VS AF Cooper, Denise C. Trivedi, Ranak B. Nelson, Karin M. Reiber, Gayle E. Eugenio, Evercita C. Beaver, Kristine A. Fan, Vincent S. TI ANTIDEPRESSANT ADHERENCE AND RISK OF CORONARY ARTERY DISEASE HOSPITALIZATIONS AMONG OLDER AND YOUNGER VETERANS WITH DEPRESSION SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Cooper, Denise C.] VA Puget Sound Hlth Care Serv, Hlth Serv Res & Dev, Seattle, WA USA. [Trivedi, Ranak B.] VA Palo Alto Hlth Care Syst, Hlth Serv Res & Dev, Menlo Pk, CA USA. [Nelson, Karin M.; Reiber, Gayle E.; Eugenio, Evercita C.; Beaver, Kristine A.; Fan, Vincent S.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A113 EP A113 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100469 ER PT J AU Dinh, J Walser, R Best, S Cloitre, M McCaslin-Rodrigo, S AF Dinh, Julie Walser, Robyn Best, Suzanne Cloitre, Marylene McCaslin-Rodrigo, Shannon TI SELF-COMPASSION IS ASSOCIATED WITH EMOTIONAL STRESS AND PERCEIVED HEALTH-RELATED FUNCTIONING IN VETERANS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Dinh, Julie] San Francisco VA Med Ctr, San Francisco, CA USA. [Walser, Robyn; Cloitre, Marylene; McCaslin-Rodrigo, Shannon] Natl Ctr PTSD, Dept Vet Affairs, Menlo Pk, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A115 EP A115 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100477 ER PT J AU Huffman, J Beale, E Celano, C Beach, S Moore, S Belcher, A Motiwala, S Gandhi, P Gaggin, H Januzzi, J AF Huffman, Jeff Beale, Eleanor Celano, Christopher Beach, Scott Moore, Shannon Belcher, Arianna Motiwala, Shweta Gandhi, Parul Gaggin, Hanna Januzzi, James TI THE GRACE (GRATITUDE RESEARCH IN ACUTE CORONARY EVENTS) TRIAL: DESIGN AND BASELINE DATA SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Huffman, Jeff; Celano, Christopher; Beach, Scott; Januzzi, James] Harvard Univ, Sch Med, Boston, MA USA. [Beale, Eleanor; Moore, Shannon; Belcher, Arianna; Motiwala, Shweta; Gandhi, Parul; Gaggin, Hanna] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A41 EP A41 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100172 ER PT J AU Huffman, JC Mastromauro, CA Beach, SR Celano, CM DuBois, CM Healy, BC Suarez, LR Rollman, BL Januzzi, JL AF Huffman, Jeff C. Mastromauro, Carol A. Beach, Scott R. Celano, Christopher M. DuBois, Christina M. Healy, Brian C. Suarez, Laura R. Rollman, Bruce L. Januzzi, James L. TI THE MOSAIC STUDY: RANDOMIZED TRIAL OF A LOW-INTENSITY COLLABORATIVE CARE INTERVENTION FOR DEPRESSION AND ANXIETY DISORDERS IN PATIENTS WITH ACUTE CARDIAC ILLNESS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Huffman, Jeff C.; Beach, Scott R.; Celano, Christopher M.; Healy, Brian C.; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Mastromauro, Carol A.; DuBois, Christina M.; Suarez, Laura R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rollman, Bruce L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A102 EP A102 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100425 ER PT J AU Huffman, JC Mastromauro, CA DuBois, CM Moore, SV Park, ER AF Huffman, Jeff C. Mastromauro, Carol A. DuBois, Christina M. Moore, Shannon V. Park, Elyse R. TI A QUALITATIVE EXAMINATION OF THE CONNECTION BETWEEN POSITIVE PSYCHOLOGICAL CONSTRUCTS AND PHYSICAL ACTIVITY FOLLOWING AN ACUTE CORONARY SYNDROME SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Huffman, Jeff C.; Park, Elyse R.] Harvard Univ, Sch Med, Boston, MA USA. [Mastromauro, Carol A.; DuBois, Christina M.; Moore, Shannon V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A77 EP A77 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100320 ER PT J AU Kelsch, CB Ironson, G O'Cleirigh, C Leserman, J Fordiani, J Schneiderman, N AF Kelsch, Courtney B. Ironson, Gail O'Cleirigh, Conall Leserman, Jane Fordiani, Joanne Schneiderman, Neil TI EMOTIONAL AND RELIGIOUS WORD CONTENT IN AN EXPRESSIVE WRITING INTERVENTION PREDICTS PHYSICAL SYMPTOMS IN HIV-POSITIVE INDIVIDUALS OVER SIX MONTHS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Kelsch, Courtney B.; Ironson, Gail; Schneiderman, Neil] Univ Miami, Coral Gables, FL 33124 USA. [O'Cleirigh, Conall] Harvard Univ, Sch Med, Boston, MA USA. [Leserman, Jane] Univ N Carolina, Chapel Hill, NC USA. [Fordiani, Joanne] VA Boston Healthcare Syst, Boston VA Res Inst Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A87 EP A87 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100363 ER PT J AU Smith, BN Koucky, EM Neylan, TC Cohen, BE AF Smith, Brian N. Koucky, Ellen M. Neylan, Thomas C. Cohen, Beth E. TI EFFECT OF PTSD ON PSYCHOSOCIAL AND FUNCTIONAL OUTCOMES IN YOUNGER VERSUS OLDER VETERANS: FINDINGS FROM THE MIND YOUR HEART STUDY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Smith, Brian N.] Boston Univ, Sch Med, Dept Psychiat, Natl Ctr PTSD,VA Boston Healthcare Syst, Boston, MA 02118 USA. [Koucky, Ellen M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A85 EP A85 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100356 ER PT J AU Talbot, LS Rao, MN Cohen, BE Mph, ARM Inslicht, SS O'Donovan, A Maguen, S Metzler, TJ Neylan, TC AF Talbot, Lisa S. Rao, Madhu N. Cohen, Beth E. Richards, Anne Inslicht, Sabra S. O'Donovan, Aoife Maguen, Shira Metzler, Thomas J. Neylan, Thomas C. TI METABOLIC RISK FACTORS, SLEEP, AND POSTTRAUMATIC STRESS DISORDER IN YOUNG, UNMEDICATED, MEDICALLY-HEALTHY ADULTS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 72nd Annual Meeting of the American-Psychosomatic-Society CY MAR 12-15, 2014 CL San Francisco, CA SP Amer Psychosomat Soc C1 [Talbot, Lisa S.; Metzler, Thomas J.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Rao, Madhu N.; Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Richards, Anne; Inslicht, Sabra S.; O'Donovan, Aoife; Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2014 VL 76 IS 3 BP A12 EP A13 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AE8FN UT WOS:000334235100052 ER PT J AU Reichert, F Kelly, V Bertolin, A Hardaker, K Salome, C King, G Mahadev, S AF Reichert, F. Kelly, V Bertolin, A. Hardaker, K. Salome, C. King, G. Mahadev, S. TI FORCED OSCILLATION TECHNIQUE AS AN INDICATOR OF AIRWAY CLOSURE SO RESPIROLOGY LA English DT Meeting Abstract DE airway closure; FOT; SBNW C1 [Reichert, F.; Bertolin, A.; Hardaker, K.; Salome, C.; King, G.; Mahadev, S.] Woolcock Inst Med Res, Glebe, NSW, Australia. [Reichert, F.] Univ Groningen, Fac Med Sci, Groningen, Netherlands. [Kelly, V] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bertolin, A.; King, G.; Mahadev, S.] Royal N Shore Hosp, Dept Resp Med, St Leonards, NSW 2065, Australia. [Hardaker, K.; King, G.] Univ Sydney, Sydney, NSW 2006, Australia. 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 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD APR PY 2014 VL 19 SU 2 SI SI BP 132 EP 132 PG 1 WC Respiratory System SC Respiratory System GA AD4RL UT WOS:000333238100354 ER PT J AU Banerjee, SC Hay, JL Geller, AC Gagne, JJ Frazier, AL AF Banerjee, Smita C. Hay, Jenifer L. Geller, Alan C. Gagne, Joshua J. Frazier, A. Lindsay TI QUITTING THE "CANCER TUBE:" A QUALITATIVE EXAMINATION OF THE PROCESS OF INDOOR TANNING CESSATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Banerjee, Smita C.; Hay, Jenifer L.] Mem Sloan Kettering Canc Ctr, New York, NY 10022 USA. [Geller, Alan C.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Gagne, Joshua J.; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. EM banerjes@mskcc.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S8 EP S8 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300028 ER PT J AU Benedict, C Traeger, L Rasheed, M Zhou, E Bustillo, N Kava, B Soloway, M Antoni, M Penedo, F AF Benedict, Catherine Traeger, Lara Rasheed, Mikal Zhou, Eric Bustillo, Natalie Kava, Bruce Soloway, Mark Antoni, Michael Penedo, Frank TI SEXUAL BOTHER IN MEN WITH ADVANCED PROSTATE CANCER UNDERGOING HORMONE THERAPY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Benedict, Catherine] Mem Sloan Kettering Canc Ctr, New York, NY 10022 USA. [Traeger, Lara] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rasheed, Mikal; Bustillo, Natalie; Antoni, Michael] Univ Miami, Miami, FL USA. [Zhou, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kava, Bruce; Soloway, Mark; Antoni, Michael] Univ Miami, Sch Med, Miami, FL USA. [Penedo, Frank] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM benedicc@mskcc.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S11 EP S11 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300040 ER PT J AU Blackmon, JE Chang, G Recklitis, CJ AF Blackmon, Jaime E. Chang, Grace Recklitis, Christopher J. TI ACCURACY OF THE DISTRESS THERMOMETER (DT) IN YOUNG ADULT CANCER SURVIVORS: COMPARISON WITH STRUCTURED DIAGNOSTIC INTERVIEW SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Blackmon, Jaime E.; Recklitis, Christopher J.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Chang, Grace] VA Boston Healthcare Syst, Brockton, MA USA. EM jaime_blackmon@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S101 EP S101 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300382 ER PT J AU Bluethmann, S Allen, JD Tom, L Chenoweth, M Leyva, B AF Bluethmann, Shirley Allen, Jennifer D. Tom, Laura Chenoweth, Matthew Leyva, Bryan TI WOMEN'S INVOLVEMENT IN SHARED DECISION MAKING FOR MAMMOGRAPHY: RESULTS FROM THE HEALTH AND RETIREMENT STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bluethmann, Shirley] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Allen, Jennifer D.; Tom, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. [Chenoweth, Matthew] Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. [Leyva, Bryan] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM shirley.m.bluethmann@uth.tmc.edu RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S193 EP S193 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300739 ER PT J AU Bober, SL Bakan, J Recklitis, CJ Garber, J Patenaude, AF AF Bober, Sharon L. Bakan, Jennifer Recklitis, Christopher J. Garber, Judy Patenaude, Andrea F. TI ADDRESSING SEXUAL DYSFUNCTION AFTER OOPHORECTOMY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bober, Sharon L.; Bakan, Jennifer; Recklitis, Christopher J.; Garber, Judy; Patenaude, Andrea F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. EM sharon_bober@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S77 EP S77 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300293 ER PT J AU Byrne, M Studts, J Hamaan, H Park, E Marcus, P Han, P AF Byrne, Margaret Studts, Jamie Hamaan, Heidi Park, Elyse Marcus, Pamela Han, Paul TI LUNG CANCER SCREENING: A NEW FRONTIER FOR BEHAVIORAL MEDICINE RESEARCH, PRACTICE, AND POLICY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Byrne, Margaret] Univ Miami, Miami, FL 33136 USA. [Studts, Jamie] Univ Kentucky, Lexington, KY USA. [Hamaan, Heidi] UT Southwestern Med Ctr, Dallas, TX USA. [Park, Elyse] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Marcus, Pamela] NCI, Bethesda, MD 20892 USA. [Han, Paul] Maine Med Ctr, Scarborough, ME USA. EM mbyrne2@med.miami.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S77 EP S77 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300294 ER PT J AU Campbell, D Bonner, L Bolkan, C Lanto, A Zivin, K Waltz, T Ruth, K Lisa, R Edmund, C AF Campbell, Duncan Bonner, Laura Bolkan, Cory Lanto, Andy Zivin, Kara Waltz, Thomas Ruth, Klap Lisa, Rubenstein Edmund, Chaney TI A PROSPECTIVE ANALYSIS OF STIGMA AS A PREDICTOR OF DEPRESSION TREATMENT PREFERENCES, MENTAL HEALTH TREATMENT ENGAGEMENT AND CARE QUALITY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Campbell, Duncan] Univ Montana, Missoula, MT 59812 USA. [Bonner, Laura; Edmund, Chaney] VA Puget Sound, Seattle, WA USA. [Bolkan, Cory] Washington State Univ, Vancouver, WA USA. [Lanto, Andy; Ruth, Klap; Lisa, Rubenstein] VA Greater Los Angeles, Los Angeles, CA USA. [Zivin, Kara] VA Ann Arbor, Ann Arbor, MI USA. [Waltz, Thomas] Eastern Michigan Univ, Ypsilanti, MI 48197 USA. EM duncan.campbell@umontana.edu NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S233 EP S233 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301144 ER PT J AU Caspi, CE Allen, JD Yang, M Tamers, S Stoddard, A Leyva, B Tucker-Seeley, R Sorensen, G AF Caspi, Caitlin E. Allen, Jennifer D. Yang, May Tamers, Sara Stoddard, Anne Leyva, Bryan Tucker-Seeley, Reginald Sorensen, Glorian TI PATHWAYS BETWEEN ACCULTURATION AND HEALTH BEHAVIORS AMONG LOW-INCOME HOUSING RESIDENTS: THE MEDIATING ROLE OF SOCIAL/CONTEXTUAL FACTORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Caspi, Caitlin E.] Univ Minnesota, Minneapolis, MN 55406 USA. [Allen, Jennifer D.; Tamers, Sara; Tucker-Seeley, Reginald; Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.; Tamers, Sara; Tucker-Seeley, Reginald; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Yang, May; Stoddard, Anne] New England Res Inst, Watertown, MA 02172 USA. [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. EM cecaspi@umn.edu RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S82 EP S82 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300310 ER PT J AU Cooley, ME Michael, K AF Cooley, Mary E. Michael, Kathleen TI BEHAVIOR CHANGE IN ADULTS ASSOCIATED WITH MANAGEMENT OF CANCER AND STROKE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. [Michael, Kathleen] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S51 EP S51 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300199 ER PT J AU Diefenbach, MA Hall, M Herrera, PC Lake, JR McWilliams, GW Hall, SJ AF Diefenbach, Michael A. Hall, Matt Herrera, Phapichaya Chaoprang Lake, Jessica R. McWilliams, Glen W. Hall, Simon J. TI AN IPOD INTERVENTION TO CONTROL HOT FLASHES IN ADVANCED PROSTATE CANCER PATIENTS ON HORMONE THERAPY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Diefenbach, Michael A.; Hall, Matt; Herrera, Phapichaya Chaoprang; Lake, Jessica R.; Hall, Simon J.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [McWilliams, Glen W.] James J Peters VA Med Ctr, Bronx, NY USA. EM michael.diefenbach@mountsinai.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S98 EP S98 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300372 ER PT J AU Evans, G Hoerster, K Stanley, M Dubbert, P AF Evans, Gina Hoerster, Katherine Stanley, Mindi Dubbert, Patricia TI A QUALITATIVE EVALUATION OF BARRIERS TO WEIGHT LOSS FOR OBESE VETERANS WITH CO-OCCURRING MENTAL ILLNESS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Evans, Gina; Stanley, Mindi] Micheal E DeBakey, Houston, TX 77030 USA. [Hoerster, Katherine] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Evans, Gina; Stanley, Mindi] Baylor Coll Med, Houston, TX 77030 USA. [Dubbert, Patricia] GRECC, VISN VA MIRECC 16, Little Rock, AR USA. EM ginae@bcm.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S144 EP S144 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300555 ER PT J AU Geller, J White, KB AF Geller, Jessica White, Karen Burns TI PROMOTING CULTURALLY SENSITIVE CANCER PREVENTION: FAITH-BASED INITIATIVE FOR LOW-INCOME LATINOS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Geller, Jessica] Univ Colorado Denver, Denver, CO 80217 USA. [White, Karen Burns] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Geller, Jessica] Tufts Univ, Sch Med, Boston, MA 02111 USA. EM jessica.geller@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S248 EP S248 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301202 ER PT J AU Goodrich, DE Littman, AJ Damschroder, LJ Goldberg, R Jones, KR AF Goodrich, David E. Littman, Alyson J. Damschroder, Laura J. Goldberg, Richard Jones, Kenneth R. TI MENTAL HEALTH MATTERS: SCREENING, PARTICIPATION AND OUTCOMES OF WEIGHT MANAGEMENT PROGRAMS FOR VETERANS WITH MENTAL HEALTH CONDITIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Goodrich, David E.; Damschroder, Laura J.] VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI 48109 USA. [Littman, Alyson J.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Goldberg, Richard] VA Maryland Healthcare Syst, Baltimore Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. [Jones, Kenneth R.] Vet Hlth Adm, Natl Ctr Hlth Promot & Dis Prevent, Durham, NC USA. EM david.goodrich2@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S50 EP S50 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300193 ER PT J AU Greer, J Sporn, N Traeger, L Temel, J Pirl, W Safren, S AF Greer, Joseph Sporn, Nora Traeger, Lara Temel, Jennifer Pirl, William Safren, Steven TI ADHERENCE TO ORAL CHEMOTHERAPY IN PATIENTS WITH ADVANCED CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Greer, Joseph; Sporn, Nora; Traeger, Lara; Temel, Jennifer; Pirl, William; Safren, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jgreer2@partners.org NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S250 EP S250 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301207 ER PT J AU Hall, KS Beckham, JC Bosworth, HB Hoerster, KD Jakupcak, M Sloane, R Crawford, E Morey, MC AF Hall, Katherine S. Beckham, Jean C. Bosworth, Hayden B. Hoerster, Katherine D. Jakupcak, Matthew Sloane, Richard Crawford, Eric Morey, Miriam C. TI PHYSICAL ACTIVITY COUNSELING IMPROVES HEALTH IN OLDER VETERANS WITH PTSD SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hall, Katherine S.; Beckham, Jean C.; Bosworth, Hayden B.; Crawford, Eric; Morey, Miriam C.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Hall, Katherine S.; Beckham, Jean C.; Bosworth, Hayden B.; Sloane, Richard; Morey, Miriam C.] Duke Univ, Med Ctr, Durham, NC USA. [Hoerster, Katherine D.; Jakupcak, Matthew] VA Puget Sound Healthcare Syst, Seattle Div, Seattle, WA USA. [Hoerster, Katherine D.; Jakupcak, Matthew] Univ Washington, Seattle, WA 98195 USA. EM katherine.hall@duke.edu NR 0 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S129 EP S129 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300494 ER PT J AU Hayman, LL Walker, LO Cooley, ME Michael, K Resnick, B Galik, E Paul, R AF Hayman, Laura L. Walker, Lorraine O. Cooley, Mary E. Michael, Kathleen Resnick, Barbara Galik, Elizabeth Paul, Regine TI NURSING IMPACT ON BEHAVIOR CHANGE ACROSS THE LIFE COURSE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hayman, Laura L.; Cooley, Mary E.; Paul, Regine] UMass Boston, Coll Nursing & Hlth Sci, Boston, MA USA. [Walker, Lorraine O.] Univ Texas Austin, Sch Nursing, Austin, TX 78712 USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Patient Care, Boston, MA 02115 USA. [Michael, Kathleen; Resnick, Barbara; Galik, Elizabeth] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S51 EP S51 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300197 ER PT J AU Hoerster, KD Jakupcak, M Hanson, R McFall, M Reiber, G Hall, K Nelson, K AF Hoerster, Katherine D. Jakupcak, Matthew Hanson, Robert McFall, Miles Reiber, Gayle Hall, Katherine Nelson, Karin TI PTSD AND DEPRESSION ARE ASSOCIATED WITH BINGE EATING DISORDER AMONG US IRAQ AND AFGHANISTAN VETERANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hoerster, Katherine D.; Jakupcak, Matthew; Hanson, Robert; McFall, Miles; Reiber, Gayle; Nelson, Karin] VA Puget Sound Healthcare Syst, Seattle Div, Seattle, WA 98108 USA. [Hoerster, Katherine D.; Jakupcak, Matthew; Hanson, Robert; McFall, Miles; Reiber, Gayle; Nelson, Karin] Univ Washington, Seattle, WA 98195 USA. [Hall, Katherine] Durham Vet Affairs Med Ctr, Durham, NC USA. [Hall, Katherine] Duke Univ, Durham, NC USA. EM Katherine.Hoerster@va.gov NR 0 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S145 EP S145 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300556 ER PT J AU Hoerster, KD Afari, N Gundy, J Evans, G Jones, K AF Hoerster, Katherine D. Afari, Niloofar Gundy, Jessica Evans, Gina Jones, Kenneth TI MENTAL HEALTH CONSIDERATIONS FOR OPTIMIZING BEHAVIORAL WEIGHT MANAGEMENT INTERVENTIONS WITH OBESE VETERANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hoerster, Katherine D.] VA Puget Sound Healthcare Syst, Seattle Div, Seattle, WA 98108 USA. [Hoerster, Katherine D.] Univ Washington, Seattle, WA 98195 USA. [Afari, Niloofar] Univ Calif San Diego, VA Ctr Excellence Stress & Mental Hlth, San Diego, CA 92103 USA. [Afari, Niloofar] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Afari, Niloofar; Gundy, Jessica] VA San Diego Healthcare Syst, San Diego, CA USA. [Evans, Gina] Houston VA HSR&D, Houston, TX USA. [Jones, Kenneth] VA Natl Ctr Hlth Promot & Dis Prevent, Durham, NC USA. EM Katherine.Hoerster@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S144 EP S144 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300554 ER PT J AU Leyva, B Allen, JD Tom, L Rustan, S Torres, MI Ospino, H AF Leyva, Bryan Allen, Jennifer D. Tom, Laura Rustan, Sarah Torres, Maria I. Ospino, Hosffman TI ORGANIZATIONAL CHARACTERISTICS ASSOCIATED WITH HEALTH PROGRAM OFFERINGS AMONG CATHOLIC PARISHES: BASELINE RESULTS OF THE CRUZA STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. [Allen, Jennifer D.; Tom, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rustan, Sarah; Torres, Maria I.] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. EM leyvavengoechb@nih.gov RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S194 EP S194 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300742 ER PT J AU Leyva, B Allen, JD Rustan, S Tom, L Galeas, A Torres, MI Ospino, H AF Leyva, Bryan Allen, Jennifer D. Rustan, Sarah Tom, Laura Galeas, Ana Torres, Maria I. Ospino, Hosffman TI WORKING WITH PARISHES FOR CANCER CONTROL: RECRUITMENT AND ENGAGEMENT STRATEGIES IN THE CRUZA STUDY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Leyva, Bryan] NCI, Gaithersburg, MD USA. [Allen, Jennifer D.; Tom, Laura; Galeas, Ana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rustan, Sarah; Torres, Maria I.] Univ Massachusetts, Boston, MA 02125 USA. [Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA. EM leyvavengoechb@nih.gov RI Allen, Jennifer/M-2113-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S194 EP S194 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300741 ER PT J AU Littman, AJ Damschroder, L Verchinia, L Lai, ZS Hoerster, K Owen, R Goodrich, D AF Littman, Alyson J. Damschroder, Laura Verchinia, Lilia Lai, Zongshan Hoerster, Katherine Owen, Richard Goodrich, David TI NATIONAL EVALUATION OF MOVE! OUTCOMES FOR VETERANS WITH AND WITHOUT MENTAL HEALTH DIAGNOSES: A RE-AIM ANALYSIS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Littman, Alyson J.; Hoerster, Katherine] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Damschroder, Laura; Verchinia, Lilia; Lai, Zongshan; Goodrich, David] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Owen, Richard] VA Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. EM alyson@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S50 EP S50 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300194 ER PT J AU Markowitz, JT Christian, AJ Harrington, KR Butler, DA Laffel, LM AF Markowitz, Jessica T. Christian, Anna J. Harrington, Kara R. Butler, Deborah A. Laffel, Lori M. TI DEPRESSION SCREENING IN PEDIATRIC TYPE 1 DIABETES (T1D); POSITIVE SCREENING SCORES AND PARENTAL RESPONSES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Markowitz, Jessica T.; Christian, Anna J.; Harrington, Kara R.; Butler, Deborah A.; Laffel, Lori M.] Joslin Diabet Ctr, Boston, MA 02215 USA. EM jessica.markowitz@joslin.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S240 EP S240 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301172 ER PT J AU Martin, E Dick, AM Scioli, E Mitchell, KS AF Martin, Emily Dick, Alexandra M. Scioli, Erica Mitchell, Karen S. TI CHANGES IN PSYCHOLOGICAL DETERMINANTS OF PHYSICAL ACTIVITY DURING A YOGA INTERVENTION FOR PTSD SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Martin, Emily] UTs MD Anderson Canc Ctr, Houston, TX 77025 USA. [Dick, Alexandra M.; Scioli, Erica; Mitchell, Karen S.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Scioli, Erica; Mitchell, Karen S.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. EM emilymar@gmail.com NR 0 TC 0 Z9 0 U1 5 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S130 EP S130 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300499 ER PT J AU Myaskovsky, L AF Myaskovsky, Larissa TI ASSOCIATION OF RACE, CULTURAL AND PSYCHOSOCIAL FACTORS, AND QUALITY OF LIFE IN VETERANS AND NON-VETERANS WITH SPINAL CORD INJURY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Myaskovsky, Larissa] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM larissa.myaskovsky@va.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S55 EP S55 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300215 ER PT J AU Myaskovsky, L Fyffe, D Botticello, A Meade, M AF Myaskovsky, Larissa Fyffe, Denise Botticello, Amanda Meade, Michelle TI THE ROLE OF PERSONAL, ENVIRONMENTAL, AND PROVIDER FACTORS IN HEALTH AND HEALTH CARE DISPARITIES IN ADULTS WITH SPINAL CORD INJURY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Myaskovsky, Larissa] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Myaskovsky, Larissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fyffe, Denise; Botticello, Amanda] Kessler Fdn Res Ctr, W Orange, NJ USA. [Fyffe, Denise; Botticello, Amanda] Rutgers State Univ, New Jersey Med Sch, W Orange, NJ USA. [Meade, Michelle] Univ Michigan, Ann Arbor, MI 48109 USA. EM larissa.myaskovsky@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S55 EP S55 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300213 ER PT J AU Pachucki, MC Christakis, NA AF Pachucki, Mark C. Christakis, Nicholas A. TI EXAMINING EATING BEHAVIORS AND NETWORK DIVERSITY INA LARGE SOCIAL NETWORK OVER TIME SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pachucki, Mark C.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Pachucki, Mark C.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Christakis, Nicholas A.] Yale Univ, Dept Med, New Haven, CT 06520 USA. EM mpachucki@partners.org NR 0 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S263 EP S263 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301262 ER PT J AU Park, ER Gareen, I Sicks, J Hyland, K Streck, J Ostroff, JS Nichter, M Rigotti, NA AF Park, Elyse R. Gareen, Ilana Sicks, JoRean Hyland, Kelly Streck, Joanna Ostroff, Jamie S. Nichter, Mark Rigotti, Nancy A. TI LUNG SCREENING'S EFFECT ON PERCEIVED RISK: IMPLICATIONS FOR TOBACCO TREATMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Park, Elyse R.; Hyland, Kelly; Streck, Joanna; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Gareen, Ilana; Sicks, JoRean] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Ostroff, Jamie S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Nichter, Mark] Univ Arizona, Sch Anthropol, Tucson, AZ USA. EM epark@partners.org RI Gareen, Ilana/I-2816-2014 OI Gareen, Ilana/0000-0002-0457-5595 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S77 EP S77 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300295 ER PT J AU Reese, JB Carpenter, KM Nelson, CJ Bober, SL Rowland, JH AF Reese, Jennifer B. Carpenter, Kristen M. Nelson, Christian J. Bober, Sharon L. Rowland, Julia H. TI NOVEL APPROACHES TO ADDRESSING SEXUAL CONCERNS FOR CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Reese, Jennifer B.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. [Carpenter, Kristen M.] Ohio State Univ, Columbus, OH 43210 USA. [Nelson, Christian J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bober, Sharon L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rowland, Julia H.] NCI, Bethesda, MD 20892 USA. EM jreese13@jhmi.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S76 EP S76 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300289 ER PT J AU Ross, K Hooker, S Masters, K Park, C Allen, LA Bekelman, D Hale-Smith, A AF Ross, Kaile Hooker, Stephanie Masters, Kevin Park, Crystal Allen, Larry A. Bekelman, David Hale-Smith, Amy TI SPIRITUAL WELL-BEING PARALLELS PHYSICAL AND PSYCHOLOGICAL DISTRESS IN PATIENTS WITH HEART FAILURE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ross, Kaile; Hooker, Stephanie; Masters, Kevin; Allen, Larry A.; Bekelman, David] Univ Colorado, Denver, CO 80217 USA. [Hooker, Stephanie; Bekelman, David] Denver Vet Affairs Med Ctr, Denver, CO USA. [Park, Crystal; Hale-Smith, Amy] Univ Connecticut, Storrs, CT USA. EM kaile.ross@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S107 EP S107 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300407 ER PT J AU Sprunck, K Ruddy, KJ Greaney, ML Meyer, ME Emmons, KM Partridge, AH AF Sprunck, Kim Ruddy, K. J. Greaney, M. L. Meyer, M. E. Emmons, K. M. Partridge, A. H. TI A QUALITATIVE STUDY TO EXPLORE THE EXISTING SUPPORTS AND UNMET NEEDS OF A RACIALLY, ETHNICALLY AND GEOGRAPHICALLY DIVERSE GROUP OF YOUNG WOMEN WITH BREAST CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Sprunck, Kim; Emmons, K. M.] DFCI, ICCBR, Boston, MA 02215 USA. [Ruddy, K. J.] Mayo Clin, Rochester, MN USA. [Greaney, M. L.] Univ RI, Kingston, RI USA. [Meyer, M. E.; Partridge, A. H.] DFCI, Boston, MA 02215 USA. EM kim_sprunckharrild@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S253 EP S253 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408301220 ER PT J AU Stokes, E Wiener, L Muriel, AC Loucas, C Pelletier, W Battles, H Zadeh, S AF Stokes, Elaina Wiener, Lori Muriel, Anna C. Loucas, Caitlyn Pelletier, Wendy Battles, Haven Zadeh, Sima TI PARENTS' USE OF DYADIC COPING STRATEGIES DURING ADJUSTMENT TO THEIR CHILD'S CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stokes, Elaina; Wiener, Lori; Battles, Haven; Zadeh, Sima] NCI, NIH, Bethesda, MD 20892 USA. [Muriel, Anna C.; Loucas, Caitlyn] Dana Farber Canc Inst, Div Pediat Psychosocial Oncol, Boston, MA 02115 USA. [Pelletier, Wendy] Alberta Childrens Prov Gen Hosp, Hematol Oncol Transplant Program, Calgary, AB, Canada. EM evstokes@gmail.com NR 0 TC 0 Z9 0 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2014 VL 47 SU 1 BP S103 EP S103 PG 1 WC Psychology, Multidisciplinary SC Psychology GA AF0MI UT WOS:000334408300390 ER EF