FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tanaka, N Liu, H Reinsberger, C Madsen, JR Bourgeois, BF Dworetzky, BA Hamalainen, MS Stufflebeam, SM AF Tanaka, N. Liu, H. Reinsberger, C. Madsen, J. R. Bourgeois, B. F. Dworetzky, B. A. Haemaelaeinen, M. S. Stufflebeam, S. M. TI Language Lateralization Represented by Spatiotemporal Mapping of Magnetoencephalography SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SPACE SEPARATION METHOD; SURFACE-BASED ANALYSIS; WADA TEST; CORTICAL ACTIVITY; MEG; DOMINANCE; RECONSTRUCTION; INTERFERENCE; LOCALIZATION; ACCURACY AB BACKGROUND AND PURPOSE: Determination of hemispheric language dominance is critical for planning epilepsy surgery. We assess the usefulness of spatiotemporal source analysis of magnetoencephalography for determining language laterality. MATERIALS AND METHODS: Thirty-five patients with epilepsy were studied. The patients performed a semantic word-processing task during MEG recording. Epochs containing language-related neuromagnetic activity were averaged after preprocessing. The averaged data between 250 and 550 ms after stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were obtained in the opercular and triangular parts of the inferior frontal gyrus, superior temporal gyrus, and supramarginal gyrus in both hemispheres. We calculated laterality indices according to 1) dSPM-amplitude method, based on the amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the number of unit dipoles with activation over a threshold in the ROIs. The threshold was determined as half of the maximum value in all ROIs for each patient. A LI 0.10 or -0.10 was considered left- or right-hemisphere dominance, respectively; a LI between -0.10 and 0.10 was considered bilateral. All patients underwent an intracarotid amobarbital procedure as part of presurgical evaluation. RESULTS: The dSPM-counting method demonstrated laterality consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%) demonstrated bilateral language representation, whereas the dSPM-amplitude method showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to the IAP was found. CONCLUSIONS: Spatiotemporal mapping of language lateralization with the dSPM-counting method may reduce the necessity for an IAP in as many as 90% of patients. C1 [Tanaka, N.; Liu, H.; Haemaelaeinen, M. S.; Stufflebeam, S. M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Reinsberger, C.; Dworetzky, B. A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Madsen, J. R.] Childrens Hosp Boston, Dept Neurosurg, Boston, MA USA. [Bourgeois, B. F.] Childrens Hosp Boston, Dept Neurol, Boston, MA USA. RP Tanaka, N (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM naoro@nmr.mgh.harvard.edu OI Dworetzky, Barbara/0000-0002-3364-2347; Liu, Hesheng/0000-0002-7233-1509 FU National Institutes of Health [P41-RR14075, R01-NS037462-07]; Mental Illness and Neuroscience Discovery Institute; NARSAD Young Investigators Award; Japan Epilepsy Research Foundation FX This work was supported by the National Institutes of Health (Grants P41-RR14075, R01-NS037462-07), Mental Illness and Neuroscience Discovery Institute, NARSAD Young Investigators Award, and Japan Epilepsy Research Foundation. NR 40 TC 8 Z9 8 U1 1 U2 6 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2013 VL 34 IS 3 BP 558 EP 563 DI 10.3174/ajnr.A3233 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 291RN UT WOS:000329846900019 PM 22878013 ER PT J AU Hoang, JK Massoglia, DP Apostol, MA Lascola, CD Eastwood, JD Kranz, PG AF Hoang, J. K. Massoglia, D. P. Apostol, M. A. Lascola, C. D. Eastwood, J. D. Kranz, P. G. TI CT-Guided Cervical Transforaminal Steroid Injections: Where Should the Needle Tip Be Located? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID NERVE ROOT BLOCKS; RADICULOPATHY AB BACKGROUND AND PURPOSE: The aim of CT-guided CTSI is to inject medication into the foraminal region where the nerve root is inflamed. The optimal location for needle placement and therapeutic delivery, however, remain uncertain. The purpose of this study was to investigate how needle positioning and angle of approach impact the transforaminal distribution of injectate. MATERIALS AND METHODS: We retrospectively reviewed fluoroscopic images from 90 CT-guided CTSI procedures for needle-tip location, needle angle, and contrast distribution. Needle-tip position was categorized as either foraminal zone, junctional, or extraforaminal. Distribution of contrast injected immediately before steroid administration was categorized as central epidural, intraforaminal, or extraforaminal in location. Needle-tip location and angle were correlated with contrast distribution. RESULTS: The needle tip was most commonly placed in the junctional position (36 cases, 40%), followed by foraminal (30 cases, 33%) and extraforaminal (24 cases, 27%) locations. Intraforaminal contrast distribution was highest when the needle location was foraminal (30/30, 100%) or junctional (35/36, 97%), compared with extraforaminal (7/24, 29%) (P value <.0001). There was no relationship between needle angle and contrast distribution. CONCLUSIONS: Needle-tip location at the outer edge of the neural foramen (junctional location) correlated well with intraforaminal distribution of contrast for CT-guided CTSI and compared favorably with injectate distribution following foraminal zone needle positioning. Junctional needle positioning may be preferred over the foraminal zone by some proceduralists. Extraforaminal needle positioning resulted in less favorable contrast distribution, which may significantly diminish the therapeutic efficacy of CTSI. C1 [Hoang, J. K.; Lascola, C. D.; Eastwood, J. D.; Kranz, P. G.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Hoang, J. K.] Duke Univ, Med Ctr, Div Neuroradiol, Durham, NC 27710 USA. [Hoang, J. K.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. [Massoglia, D. P.] Ralph Johnson VA Med Ctr, Dept Radiol, Charleston, SC USA. [Apostol, M. A.] Clin Radiologists SC, Springfield, IL USA. RP Hoang, JK (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808,Erwin Rd, Durham, NC 27710 USA. EM jennykh@gmail.com RI Hoang, Jenny/B-7779-2016; Kranz, Peter/B-2471-2016; Lascola, Christopher/B-9126-2017 OI Hoang, Jenny/0000-0002-6715-0922; Kranz, Peter/0000-0001-5410-7135; Lascola, Christopher/0000-0002-8031-782X NR 12 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2013 VL 34 IS 3 BP 688 EP 692 DI 10.3174/ajnr.A3266 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 291RN UT WOS:000329846900039 PM 22954742 ER PT J AU Park, ES Woods, DC White, YAR Tilly, JL AF Park, Eun-Sil Woods, Dori C. White, Yvonne A. R. Tilly, Jonathan L. TI Oogonial Stem Cells Isolated from Ovaries of Adult Transgenic Female Mice Generate Functional Eggs and Offspring Following Intraovarian Transplantation SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI) CY MAR 20-23, 2013 CL Orlando, FL SP Soc Gynecol Invest C1 [Park, Eun-Sil; Woods, Dori C.; White, Yvonne A. R.; Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Park, Eun-Sil; Woods, Dori C.; White, Yvonne A. R.; Tilly, Jonathan L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 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 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2013 VL 20 IS S3 SU 3 BP 75A EP 76A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 287LK UT WOS:000329543100046 ER PT J AU Park, ES Tilly, JL AF Park, Eun-Sil Tilly, Jonathan L. TI Bone Morphogenetic Protein 4 Signaling Promotes Differentiation of Adult Mouse Ovary-Derived Oogonial Stem Cells into Oocytes In Vitro SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI) CY MAR 20-23, 2013 CL Orlando, FL SP Soc Gynecol Invest C1 [Park, Eun-Sil; Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Park, Eun-Sil; Tilly, Jonathan L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2013 VL 20 IS S3 SU 3 BP 189A EP 190A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 287LK UT WOS:000329543100432 ER PT J AU Woods, DC Tilly, JL AF Woods, Dori C. Tilly, Jonathan L. TI Oogonial Stem Cells: A Source for Autologous Germline Mitochondria SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI) CY MAR 20-23, 2013 CL Orlando, FL SP Soc Gynecol Invest C1 [Woods, Dori C.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept OB GYN, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2013 VL 20 IS S3 SU 3 BP 190A EP 190A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 287LK UT WOS:000329543100435 ER PT J AU Jonker, SS Louey, S Thornburg, KL Faber, JJ Giraud, GD AF Jonker, Sonnet S. Louey, Samantha Thornburg, Kent L. Faber, J. Job Giraud, George D. TI Cardiac Myocyte Growth Dynamics Change at Birth SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI) CY MAR 20-23, 2013 CL Orlando, FL SP Soc Gynecol Invest C1 [Jonker, Sonnet S.; Louey, Samantha; Thornburg, Kent L.; Faber, J. Job; Giraud, George D.] OHSU, Heart Res Ctr, Portland, OR USA. [Jonker, Sonnet S.; Louey, Samantha; Thornburg, Kent L.; Giraud, George D.] OHSU, Portland, OR 97201 USA. [Giraud, George D.] Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2013 VL 20 IS S3 SU 3 BP 212A EP 212A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 287LK UT WOS:000329543100508 ER PT J AU Bunce, EE Kaimal, AJ Smith, NA AF Bunce, Emily E. Kaimal, Anjali J. Smith, Nicole A. TI Pregnancy in Women with Breast Cancer: How Do Outcomes Differ in Pregnancy Associated Breast Cancer and Breast Cancer Diagnosed Prior to Pregnancy? SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 60th Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI) CY MAR 20-23, 2013 CL Orlando, FL SP Soc Gynecol Invest C1 [Bunce, Emily E.; Smith, Nicole A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bunce, Emily E.; Kaimal, Anjali J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2013 VL 20 IS S3 SU 3 BP 325A EP 326A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 287LK UT WOS:000329543100896 ER PT J AU Ard, KL Chan, BT Milner, DA Farmer, PE Koenig, SP AF Ard, Kevin L. Chan, Brian T. Milner, Danny A., Jr. Farmer, Paul E. Koenig, Serena P. TI Peritoneal Tuberculosis in a Pregnant Woman from Haiti, United States SO EMERGING INFECTIOUS DISEASES LA English DT Letter C1 [Ard, Kevin L.; Chan, Brian T.; Milner, Danny A., Jr.; Farmer, Paul E.; Koenig, Serena P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ard, Kevin L.; Chan, Brian T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ard, KL (reprint author), Brigham & Womens Hosp, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM kard@partners.org NR 10 TC 1 Z9 1 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR PY 2013 VL 19 IS 3 BP 514 EP 516 DI 10.3201/eid1903.121109 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268LU UT WOS:000328173000034 PM 23750361 ER PT J AU Sherman, ME Knudsen, KJ Sweeney, HA Tam, K Musuuza, J Koroukian, SM AF Sherman, Marion E. Knudsen, Kraig J. Sweeney, Helen Anne Tam, Kwok Musuuza, Jackson Koroukian, Siran M. TI Analysis of Causes of Death for All Decedents in Ohio With and Without Mental Illness, 2004-2007 SO PSYCHIATRIC SERVICES LA English DT Article ID PREMATURE MORTALITY; MEDICAID POPULATION; CARE; DISORDERS; QUALITY; CANCER; INJURY AB Objective: This study compared causes of death, crude mortality rates, and standardized mortality ratios (SMRs) between decedents with mental illness in Ohio's publicly funded mental health system ("mental illness decedents") and all Ohio decedents. Methods: Ohio death certificates and Ohio Department of Mental Health service utilization data were used to assess mortality among decedents from 2004 to 2007. Age-adjusted SMRs and age-adjusted mortality rates were calculated across race and sex strata. Results: Mental illness decedents accounted for 3.3% of all 438,749 Ohio deaths. Age-adjusted SMRs varied widely across the race and sex strata and by cause of death. Nonblacks with or without mental illness showed higher SMRs than blacks. Nonblack females with mental illness showed the highest SMRs in injury-related deaths. Higher SMRs were found for deaths associated with substance abuse; mental illness; diabetes; issues related to the nervous, cardiovascular, or respiratory systems; and injury. With and without mental illness, the top cause of death was violence for youths and cardiovascular disease for adults >35. Conclusions: Deaths from injury and violence, especially among those <35, should be specifically addressed to reduce excess mortality for persons with mental illness. Mental health care should be integrated with primary care to better manage chronic disease, especially cardiovascular disease. Methodological contributions included use of linked files to compare SMR and leading causes of death between mental illness decedents and all Ohio decedents. More research is needed on patterns in cause of death and any interactions from demographic characteristics and mental illness. Health care data silos must be bridged between private and public sectors and the Departments of Veterans Affairs and Defense. C1 [Sherman, Marion E.] VA Gulf Coast Vet Hlth Care Syst, US Dept Vet Affairs, Biloxi, MS 39531 USA. [Knudsen, Kraig J.; Sweeney, Helen Anne] Case Western Reserve Univ, Ohio Dept Mental Hlth, Dept Res & Evaluat, Cleveland, OH 44106 USA. [Musuuza, Jackson] Case Western Reserve Univ, Dept Epidemiol & Biostatist, Cleveland, OH 44106 USA. [Musuuza, Jackson] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53706 USA. RP Sherman, ME (reprint author), VA Gulf Coast Vet Hlth Care Syst, US Dept Vet Affairs, 400 Vet Ave, Biloxi, MS 39531 USA. EM marion.sherman@va.gov FU ODMH; Clinical and Translational Science Collaborative of Cleveland; National Center for Advancing Translational Sciences component of the National Institutes of Health (NIH) [UL1TR000439]; NIH Roadmap for Medical Research FX Dr. Koroukian was funded in part by a contract from ODMH, by a pilot grant from the Clinical and Translational Science Collaborative of Cleveland, by grant UL1TR000439 from the National Center for Advancing Translational Sciences component of the National Institutes of Health (NIH), and by an NIH Roadmap for Medical Research. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of NIH. The authors thank Meatal Patel, M. P. H., M. B. A. candidate, for her assistance in manuscript preparation. NR 20 TC 2 Z9 2 U1 1 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2013 VL 64 IS 3 BP 245 EP 251 DI 10.1176/appi.ps.201100238 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255UM UT WOS:000327265600008 PM 23318767 ER PT J AU Drapalski, AL Lucksted, A Perrin, PB Aakre, JM Brown, CH DeForge, BR Boyd, JE AF Drapalski, Amy L. Lucksted, Alicia Perrin, Paul B. Aakre, Jennifer M. Brown, Clayton H. DeForge, Bruce R. Boyd, Jennifer E. TI A Model of Internalized Stigma and Its Effects on People With Mental Illness SO PSYCHIATRIC SERVICES LA English DT Article ID SCHIZOPHRENIA SPECTRUM DISORDERS; STRESS-COPING MODEL; SELF-EFFICACY SCALE; PERCEIVED DISCRIMINATION; EUROPEAN COUNTRIES; GAMIAN-EUROPE; OUTPATIENTS; EMPOWERMENT; DEPRESSION; VALIDATION AB Objectives: The investigators aimed to examine the prevalence of internalized stigma among individuals with serious mental illness and to construct and test a hypothesized model of the interrelationships among internalized stigma, self-concept, and psychiatric symptoms. Methods: One hundred individuals, most of whom were African American and had a diagnosis of serious mental illness, were receiving mental health services from one of three community outpatient mental health programs or one Veterans Affairs medical center. They completed an interview that included measures of internalized stigma, psychiatric symptoms, self-esteem, self-efficacy, and recovery orientation. Structural equation modeling (SEM) was used to examine the interrelationships among these variables. Results: Thirty-five percent of participants reported moderate to severe levels of internalized stigma, which was not significantly associated with any demographic variable or diagnosis. However, greater internalized stigma was associated with lower levels of self-esteem, self-efficacy, and recovery orientation, as well as with more severe psychiatric symptoms. The SEM produced a nonsignificant chi square statistic and other fit indices indicative of a good model fit (goodness-of-fit index=.96, root mean square error of approximation=.011). Conclusions: Results suggest that internalized stigma was prevalent and problematic among individuals with serious mental illness. There may be multiple pathways through which stigma and discrimination lead to negative outcomes, suggesting that interventions to reduce internalized stigma need to target multiple points along these pathways in order to be effective. C1 [Drapalski, Amy L.; Lucksted, Alicia; Aakre, Jennifer M.; Brown, Clayton H.] VA Maryland Healthcare Syst, MIRECC Annex, Mental Illness Res Educ & Clin Ctr, Vet Affairs VA Capitol Network,Vet Integrated Ser, Baltimore, MD 21201 USA. [Lucksted, Alicia] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Brown, Clayton H.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Perrin, Paul B.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [DeForge, Bruce R.] Univ Maryland, Sch Social Work, Baltimore, MD 21201 USA. [Boyd, Jennifer E.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Boyd, Jennifer E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Drapalski, AL (reprint author), VA Maryland Healthcare Syst, MIRECC Annex, Mental Illness Res Educ & Clin Ctr, Vet Affairs VA Capitol Network,Vet Integrated Ser, 7th Floor,10 N Greene St, Baltimore, MD 21201 USA. EM amy.drapalski@va.gov FU VA Capitol Network (Veterans Integrated Service Network 5) Mental Illness Research, Education and Clinical Center FX This article is the result of work supported by the VA Capitol Network (Veterans Integrated Service Network 5) Mental Illness Research, Education and Clinical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs or the U.S. government. NR 32 TC 43 Z9 43 U1 4 U2 33 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2013 VL 64 IS 3 BP 264 EP 269 DI 10.1176/appi.ps.001322012 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255UM UT WOS:000327265600011 PM 23573532 ER PT J AU Fard, AM Gupta, S Jalali, B AF Fard, Ali M. Gupta, Shalabh Jalali, Bahram TI Photonic time-stretch digitizer and its extension to real-time spectroscopy and imaging SO LASER & PHOTONICS REVIEWS LA English DT Article DE Photonic analog-to-digital conversion; time stretch; optical communications; optical links; real-time spectroscopy; optical sampling; optical kerr nonlinearity; high-throughput imaging ID TO-DIGITAL CONVERTER; OPTICAL-FIBERS; PARAMETRIC AMPLIFICATION; DISPERSION COMPENSATION; POLYMER MODULATORS; A/D CONVERTERS; CONVERSION; WAVELENGTH; SYSTEMS; RESOLUTION AB Real-time wideband digitizers are the key building block in many systems including oscilloscopes, signal intelligence, electronic warfare, and medical diagnostics systems. Continually extending the bandwidth of digitizers has hence become a central challenge in electronics. Fortunately, it has been shown that photonic pre-processing of wideband signals can boost the performance of electronic digitizers. In this article, the underlying principle of the time-stretch analog-to-digital converter (TSADC) that addresses the demands on resolution, bandwidth, and spectral efficiency is reviewed. In the TSADC, amplified dispersive Fourier transform is used to slow down the analog signal in time and hence to compress its bandwidth. Simultaneous signal amplification during the time-stretch process compensates for parasitic losses leading to high signal-to-noise ratio. This powerful concept transforms the analog signal's time scale such that it matches the slower time scale of the digitizer. A summary of time-stretch technology's extension to high-throughput single-shot spectroscopy, a technique that led to the discovery of optical rouge waves, is also presented. Moreover, its application in high-throughput imaging, which has recently led to identification of rogue cancer cells in blood with record sensitivity, is discussed. C1 [Fard, Ali M.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Fard, Ali M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gupta, Shalabh] Indian Inst Technol, Dept Elect Engn, Bombay 400076, Maharashtra, India. [Jalali, Bahram] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA. [Jalali, Bahram] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA. [Jalali, Bahram] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. [Jalali, Bahram] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. RP Fard, AM (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM mfard.ali@mgh.harvard.edu FU US Defense Advanced Research Projects Agency (DARPA); National Science Foundation (NSF) through CIAN-ERC FX The authors would like to acknowledge the support by US Defense Advanced Research Projects Agency (DARPA) and National Science Foundation (NSF) through CIAN-ERC. NR 123 TC 27 Z9 29 U1 3 U2 31 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1863-8880 EI 1863-8899 J9 LASER PHOTONICS REV JI Laser Photon. Rev. PD MAR PY 2013 VL 7 IS 2 BP 207 EP 263 DI 10.1002/lpor.201200015 PG 57 WC Optics; Physics, Applied; Physics, Condensed Matter SC Optics; Physics GA 238HD UT WOS:000325934300006 ER PT J AU Shetty, S Fisher, MC Ahmed, AR AF Shetty, Shawn Fisher, Mark C. Ahmed, A. Razzaque TI Review on the Influence of Protocol Design on Clinical Outcomes in Rheumatoid Arthritis Treated with Rituximab SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; RANDOMIZED CONTROLLED-TRIAL; DISEASE-ACTIVITY; EULAR RECOMMENDATIONS; INADEQUATE RESPONSE; AMERICAN-COLLEGE; DOUBLE-BLIND; CONSENSUS STATEMENT; EFFICACY; SAFETY AB OBJECTIVE: To critically analyze the influence of protocol design on clinical outcome in patients with rheumatoid arthritis (RA) treated with rituximab. DATA SOURCES: A PubMed and EMBASE search (January 2000-January 2012) using the key words rheumatoid arthritis and rituximab was performed. STUDY SELECTION AND DATA EXTRACTION: A search of English-language studies from the data sources was conducted for randomized, double-blind, placebo-controlled studies with 100 patients or more assessing the efficacy and safety of rituximab in the treatment of RA. From these studies, 2 authors independently extracted, compiled, and aggregated the data. DATA SYNTHESIS: Eight studies met the inclusion criteria. In these studies, some patients had not been treated with tumor necrosis factor-alfa (TNF-alpha) inhibitors, while most did not respond to it. The variables compared included dose (500 vs 1000 mg), duration of study (24 vs 48 weeks), and number of cycles (1 vs 2). They were statistically analyzed using the c 2 test. There was a statistically significant difference in the response to rituximab compared to the control (methotrexate) (p < 0.001). In patients who were studied for only 24 weeks, given 500 or 1000 mg for 1 or 2 cycles, a 90% or greater response rate was reported in those who achieved an ACR 20, but no statistically significant differences were observed (p = 0.75). In patients studied for 48 weeks who received 2 cycles of either 500 mg or 1000 mg of rituximab and achieved an ACR 20, a statistically significant difference (p < 0.001) was observed in those who received a dose of 1000 mg for 2 cycles (42.77% vs 67.49%). CONCLUSIONS: In patients who are nonresponsive to disease-modifying antirheumatic drugs and TNF-alpha inhibitors, rituximab may be a promising and well-tolerated biologic agent. The capacity of rituximab to produce long-term, sustained remissions could not be evaluated because the duration of the studies was limited to 24 weeks or 48 weeks. Studies with longer periods of observation are warranted. C1 [Shetty, Shawn; Ahmed, A. Razzaque] Ctr Blistering Dis, Boston, MA USA. [Fisher, Mark C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Rheumatol Serv,Dept Med, Boston, MA USA. RP Ahmed, AR (reprint author), Ctr Blistering Dis, Boston, MA USA. EM arahmedmd@msn.com NR 57 TC 3 Z9 3 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2013 VL 47 IS 3 BP 311 EP 323 DI 10.1345/aph.1R574 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225TZ UT WOS:000324987200006 PM 23447479 ER PT J AU Anderson, DM Pesaturo, KA Casavant, J Ramsey, EZ AF Anderson, Debra M. Pesaturo, Kimberly A. Casavant, Jonathan Ramsey, E. Zachary TI Alteplase for the Treatment of Catheter Occlusion in Pediatric Patients SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; CENTRAL VENOUS CATHETERS; ACCESS DEVICES; LINES; RESTORATION; EFFICACY; TRIAL AB OBJECTIVE: To review the literature pertaining to the efficacy of alteplase for restoration of patency of occluded venous and dialysis catheters in pediatric patients. DATA SOURCES: A MEDLINE search was conducted and cross-referenced with an EMBASE search through November 2012. Search terms included alteplase, tissue plasminogen activator, and catheter. STUDY SELECTION AND DATA EXTRACTION: Search results were limited to humans, English language, and ages from neonates to 18 years. Pertinent studies discussing efficacy of alteplase for restoration of occluded venous or dialysis catheter function were included. Case reports, review articles, and studies that specified inclusion of hemophilia patients or more than 75% of children with malignancy were excluded. DATA SYNTHESIS: Fibrinolytics are the drug class of choice for restoration of patency (defined as the ability to withdraw a blood sample) of thrombus-occluded catheters. The trials used to support Food and Drug Administration approval of alteplase for central venous catheter (CVC) occlusions generally had low pediatric enrollment; however, additional small studies are available that support use of alteplase for this indication in children. Alteplase doses of 0.5-2 mg instilled into the lumen of a CVC with dwell times ranging from 30 to more than 240 minutes plus the potential for repeat dosing were reported. Overall efficacy ranged from approximately 50% to 90%, with greater efficacy generally reported with larger doses and longer dwell times. Alteplase doses of 2-2.5 mg with dwell times of 60120 minutes were observed in 2 studies of occluded peritoneal or hemodialysis catheters, in which efficacy was reported in 57-100% of cases. Limitations of current studies of alteplase for catheter occlusion in children include small study populations and relative lack of pediatric-specific prospective trials. CONCLUSIONS: Alteplase appears to show efficacy for treatment of thrombus-related venous catheter occlusion in pediatric patients; however, data regarding its use in occluded dialysis catheters are limited. C1 [Anderson, Debra M.] Harrington Mem Hosp, Dept Pharm, Southbridge, MA USA. [Pesaturo, Kimberly A.] Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, Boston, MA USA. [Casavant, Jonathan] VA Puget Sound Hlth Care Syst, Dept Pharm, Seattle, WA USA. [Ramsey, E. Zachary] Childrens Hosp Philadelphia, Dept Pharm, Philadelphia, PA USA. RP Anderson, DM (reprint author), Harrington Mem Hosp, Dept Pharm, Southbridge, MA USA. EM danderso@harringtonhospital.org NR 17 TC 5 Z9 5 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2013 VL 47 IS 3 BP 405 EP 410 DI 10.1345/aph.1Q483 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225TZ UT WOS:000324987200016 PM 23463740 ER PT J AU De Luca, G Gibson, M Cutlip, D Huber, K Dudek, D Bellandi, F Noc, M Maioli, M Zorman, S Zeymer, U Secco, GG Gabriel, HM Emre, A Arntz, HR Rakowski, T Gyongyosi, M van't Hof, AWJ AF De Luca, Giuseppe Gibson, Michael Cutlip, Donald Huber, Kurt Dudek, Dariusz Bellandi, Francesco Noc, Marko Maioli, Mauro Zorman, Simona Zeymer, Uwe Secco, Gioel Gabrio Gabriel, Henrique Mesquita Emre, Ayse Arntz, Hans-Richard Rakowski, Tomasz Gyongyosi, Maryann van't Hof, Arnoud W. J. CA EGYPT Cooperation TI Impact of multivessel disease on myocardial perfusion and survival among patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitors SO ARCHIVES OF CARDIOVASCULAR DISEASES LA English DT Article DE Primary angioplasty; Multivessel disease; Myocardial Perfusion; Mortality ID META-REGRESSION ANALYSIS; IIB-IIIA INHIBITORS; TERM-FOLLOW-UP; PRIMARY ANGIOPLASTY; RANDOMIZED-TRIALS; THROMBOLYTIC THERAPY; INFARCTION; METAANALYSIS; REPERFUSION; REVASCULARIZATION AB Background. - Although primary angioplasty achieves thrombolysis in myocardial infarction (TIMI) 3 flow in most patients with ST-elevation myocardial infarction, epicardial recanalization does not guarantee optimal perfusion in a large proportion of patients. The influence of multivessel disease on myocardial reperfusion and survival after primary angioplasty has not been extensively investigated. Aim. - To evaluate the impact of multivessel disease on myocardial perfusion and survival in a large cohort of patients with ST-elevation myocardial infarction treated with angioplasty and glycoprotein (GP) IIb/IIIa inhibitors. Methods. - This analysis is based on 1494 patients undergoing primary angioplasty included in the EGYPT database. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak creatine kinase-MB (CK-MB). Follow-up data were collected between 30 days and 1 year after primary angioplasty. Results. - Multivessel disease was observed in 870 patients (58.2%). The extent of coronary artery disease was associated with age, diabetes, hypertension, previous myocardial infarction, previous revascularization, abciximab treatment and longer ischaemic time, and was independently associated with impaired angiographic myocardial perfusion (adjusted odds ratio 1.18, 95% confidence interval [CI] 1.01-1.40, P=0.049). At 208 160 days, the extent of coronary artery disease was independently associated with higher mortality (adjusted hazard ratio 1.54, 95% CI 1.06-2.24, P=0.022). Conclusions. - Among patients with ST-elevation myocardial infarction undergoing primary angioplasty with GP IIb/IIIa inhibitor treatment, the extent of coronary artery disease was independently associated with impaired myocardial perfusion and survival. (C) 2013 Elsevier Masson SAS. All rights reserved. C1 [De Luca, Giuseppe; Secco, Gioel Gabrio] Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy. [Gibson, Michael] Beth Israel Deaconess Med Ctr, Div Cardiovasc, TIMI Study Grp, Boston, MA 02215 USA. [Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA. [Huber, Kurt] Wilhelminenspital Stadt Wien, Dept Med Cardiol & Emergency Med 3, Vienna, Austria. [Dudek, Dariusz; Rakowski, Tomasz] Jagiellonian Univ, Inst Cardiol, Dept Cardiol 2, Krakow, Poland. [Bellandi, Francesco; Maioli, Mauro] Prato Hosp, Div Cardiol, Prato, Italy. [Noc, Marko; Zorman, Simona] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia. [Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany. [Gabriel, Henrique Mesquita] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal. [Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Istanbul, Turkey. [Arntz, Hans-Richard] Campus Benjamin Franklin, Charite, Med Klin 2, Berlin, Germany. [Gyongyosi, Maryann] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [van't Hof, Arnoud W. J.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands. RP De Luca, G (reprint author), Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy. EM giuseppe.deluca@maggioreosp.novara.it NR 29 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1875-2136 J9 ARCH CARDIOVASC DIS JI Arch. Cardiovasc. Dis. PD MAR PY 2013 VL 106 IS 3 BP 155 EP 161 DI 10.1016/j.acvd.2012.12.007 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 214SA UT WOS:000324154900005 PM 23582677 ER PT J AU LaLonde, JM Le-Khac, M Jones, DM Courter, JR Park, J Schon, A Princiotto, AM Wu, XL Mascola, JR Freire, E Sodroski, J Madani, N Hendrickson, WA Smith, AB AF LaLonde, Judith M. Le-Khac, Matthew Jones, David M. Courter, Joel R. Park, Jongwoo Schoen, Arne Princiotto, Amy M. Wu, Xueling Mascola, John R. Freire, Ernesto Sodroski, Joseph Madani, Navid Hendrickson, Wayne A. Smith, Amos B., III TI Structure-Based Design and Synthesis of an HIV-1 Entry Inhibitor Exploiting X-ray and Thermodynamic Characterization SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIV; gp120; CD4; entry inhibitor; structure-based drug design; thermodynamics; X-ray crystallography; viral inhibition; protein-protein interactions ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEINS; GP120; CD4; BINDING; RECEPTOR; ANTIBODY; COMPLEX; MIMICS AB The design, synthesis, thermodynamic and crystallographic characterization of a potent, broad spectrum, second-generation HIV-1 entry inhibitor that engages conserved carbonyl hydrogen bonds within gp120 has been achieved. The optimized antagonist exhibits a submicromolar binding affinity (110 nM) and inhibits viral entry of clade B and C viruses (IC50 geometric mean titer of 1.7 and 14.0 mu M, respectively), without promoting CD4-independent viral entry. The thermodynamic signatures indicate a binding preference for the (R,R)- over the (S,S)-enantiomer. The crystal structure of the small-molecule/gp120 complex reveals the displacement of crystallographic water and the formation of a hydrogen bond with a backbone carbonyl of the bridging sheet. Thus, structure-based design and synthesis targeting the highly conserved and structurally characterized CD4-gp120 interface is an effective tactic to enhance the neutralization potency of small-molecule HIV-1 entry inhibitors. C1 [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Le-Khac, Matthew] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. [Le-Khac, Matthew; Hendrickson, Wayne A.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Jones, David M.; Courter, Joel R.; Park, Jongwoo; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Princiotto, Amy M.; Sodroski, Joseph; Madani, Navid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wu, Xueling; Mascola, John R.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Sodroski, Joseph] Ragon Inst MGH MIT & Harvard, Boston, MA 02115 USA. [Hendrickson, Wayne A.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. RP LaLonde, JM (reprint author), Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. EM jlalonde@brynmawr.edu; wayne@xtl.cumc.columbia.edu; smithab@sas.upenn.edu FU NIH [GM 56550, AI090682-01]; NIH Intramural IATAP; NIAID programs; Ragon Institute of MGH; Ragon Institute of MIT; Ragon Institute of Harvard FX Funding was provided by NIH GM 56550 to J.M.L., E.F., WA.H., A.B.S., and J.S. and by NIH Intramural IATAP and NIAID programs to J.R.M. and J.S. Funding to N.M. was provided by NIH AI090682-01. N.M. and J.S. were also supported by Ragon Institute of MGH, MIT, and Harvard. NR 27 TC 27 Z9 27 U1 4 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAR PY 2013 VL 4 IS 3 BP 338 EP 343 DI 10.1021/ml300407y PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 207JD UT WOS:000323593800006 PM 23667716 ER PT J AU Mandel, M Askenazi, M Zhang, Y Marto, JA AF Mandel, Micha Askenazi, Manor Zhang, Yi Marto, Jarrod A. TI VARIANCE FUNCTION ESTIMATION IN QUANTITATIVE MASS SPECTROMETRY WITH APPLICATION TO ITRAQ LABELING SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Heteroscedasticity; iTRAQ; mixture model; nuisance parameter; proteomics ID MICROARRAY DATA; IMMUNOASSAY; PROTEOMICS AB This paper describes and compares two methods for estimating the variance function associated with iTRAQ (isobaric tag for relative and absolute quantitation) isotopic labeling in quantitative mass spectrometry based proteomics. Measurements generated by the mass spectrometer are proportional to the concentration of peptides present in the biological sample. However, the iTRAQ reporter signals are subject to errors that depend on the peptide amounts. The variance function of the errors is therefore an essential parameter for evaluating the results, but estimating it is complicated, as the number of nuisance parameters increases with sample size while the number of replicates for each peptide remains small. Two experiments that were conducted with the sole goal of estimating the variance function and its stability over time are analyzed, and the resulting estimated variance function is used to analyze an experiment targeting aberrant signaling cascades in cells harboring distinct oncogenic mutations. Methods for constructing conservative p-values and confidence intervals are discussed. C1 [Mandel, Micha] Hebrew Univ Jerusalem, Dept Stat, IL-91905 Jerusalem, Israel. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Zhang, Yi] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Zhang, Yi] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. RP Mandel, M (reprint author), Hebrew Univ Jerusalem, Dept Stat, IL-91905 Jerusalem, Israel. EM msmic@huji.ac.il NR 21 TC 1 Z9 1 U1 0 U2 5 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD MAR PY 2013 VL 7 IS 1 BP 1 EP 24 DI 10.1214/12-AOAS572 PG 24 WC Statistics & Probability SC Mathematics GA 197DH UT WOS:000322828900001 ER PT J AU Schwartzman, A Jaffe, A Gavrilov, Y Meyer, CA AF Schwartzman, Armin Jaffe, Andrew Gavrilov, Yulia Meyer, Clifford A. TI MULTIPLE TESTING OF LOCAL MAXIMA FOR DETECTION OF PEAKS IN CHIP-SEQ DATA SO ANNALS OF APPLIED STATISTICS LA English DT Article DE False discovery rate; kernel smoothing; matched filter; Poisson sequence; topological inference ID NONHOMOGENEOUS POISSON-PROCESS; INTENSITY FUNCTION; MODEL AB A topological multiple testing approach to peak detection is proposed for the problem of detecting transcription factor binding sites in ChIP-Seq data. After kernel smoothing of the tag counts over the genome, the presence of a peak is tested at each observed local maximum, followed by multiple testing correction at the desired false discovery rate level. Valid p-values for candidate peaks are computed via Monte Carlo simulations of smoothed Poisson sequences, whose background Poisson rates are obtained via linear regression from a Control sample at two different scales. The proposed method identifies nearby binding sites that other methods do not. C1 [Schwartzman, Armin; Gavrilov, Yulia; Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Schwartzman, Armin; Gavrilov, Yulia; Meyer, Clifford A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Jaffe, Andrew] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Jaffe, Andrew] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. RP Schwartzman, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 450 Brookline Ave,CLS-11007, Boston, MA 02115 USA. EM armins@hsph.harvard.edu; andrew.jaffe@libd.org; yuliagavrilov@gmail.com; cliff@jimmy.harvard.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU Claudia Adams Barr Program in Cancer Research; William F. Milton Fund; NIH [P01-CA134294, R01-CA157528]; Predoctoral Biostatistics Training in Genetics/Genomics [T32 GM074906] FX Supported in part by the Claudia Adams Barr Program in Cancer Research, the William F. Milton Fund and NIH Grants P01-CA134294 and R01-CA157528.; Supported in part by T32 GM074906 Predoctoral Biostatistics Training in Genetics/Genomics. NR 26 TC 5 Z9 5 U1 1 U2 3 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD MAR PY 2013 VL 7 IS 1 BP 471 EP 494 DI 10.1214/12-AOAS594 PG 24 WC Statistics & Probability SC Mathematics GA 197DH UT WOS:000322828900020 PM 25411587 ER PT J AU Singh, S Digumarthy, SR Back, A Shepard, JAO Kalra, MK AF Singh, Sarabjeet Digumarthy, Subba R. Back, Anni Shepard, Jo-anne O. Kalra, Mannudeep K. TI Radiation dose reduction for chest CT with non-linear adaptive filters SO ACTA RADIOLOGICA LA English DT Article DE CT radiation dose reduction; non-linear adaptive filters; postprocessing software; chest CT image quality; low dose chest CT; image noise reduction ID IMAGE QUALITY; COMPUTED-TOMOGRAPHY; ABDOMEN; ADULTS AB Background: CT radiation dose reduction results in increased noise or graininess of images which affects the diagnostic information. One of the approaches to lower radiation exposure to patients is to reduce image noise with the use of image processing software in low radiation dose images. Purpose: To assess image quality and accuracy of non-linear adaptive filters (NLAF) at low dose chest CT. Material and Methods: In an IRB approved prospective study, 24 patients (mean age, 63 +/- 7.3 years; M: F ratio, 11: 13) gave informed consent for acquisition of four additional chest CT image series at 150, 110, 75, and 40 mAs (baseline image series) on a 64-slice MDCT over an identical 10-cm length. NLAF was used to process three low dose (110, 75, and 40 mAs) image series (postprocessed image series). Two radiologists reviewed baseline and postprocessed images in a blinded manner for image quality. Objective noise, CT attenuation values, patient weight, transverse diameters, CTDIvol, and DLP were recorded. Statistical analysis was performed using parametric and non-parametric tests for comparing postprocessed and baseline images. Results: No lesions were missed on baseline or postprocessed CT images (n = 80 lesions, 73 lesions <1 cm). At 40 mAs, subjective noise in mediastinal window settings were graded as unacceptable in baseline images and acceptable in postprocessed images. Visibility of smaller structures improved from suboptimal visibility in baseline images at 40 mAs to excellent in postprocessed images at 40 mAs. No major artifacts were seen due to NLAF postprocessing, except for minor beam hardening artifacts not affecting diagnostic decision-making (14/22) in both baseline and postprocessed image series. Diagnostic confidence for chest CT was improved to fully confident in postprocessed images at 40 mAs. Compared to baseline images, postprocessing reduced objective noise by 26% (14.2 +/- 4.7/19.2 +/- 6.4), 31.5% (15.2 +/- 4.7/22.2 +/- 5.7), and 41.5% (16.9 +/- 6/28.9 +/- 10.2) at 110 mAs, 75 mAs, and 40 mAs tube current-time product levels. Conclusion: Applications of NLAF can help reduce tube current down to 40 mAs for chest CT while maintaining lesion conspicuity and image quality. C1 [Singh, Sarabjeet; Digumarthy, Subba R.; Shepard, Jo-anne O.; Kalra, Mannudeep K.] Massachusetts Gen Hosp Imaging, Boston, MA USA. [Back, Anni] ContextVis AB, Linkoping, Sweden. RP Singh, S (reprint author), Massachusetts Gen Hosp Imaging, Boston, MA USA. EM ssingh6@partners.org NR 21 TC 3 Z9 3 U1 0 U2 2 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD MAR PY 2013 VL 54 IS 2 BP 169 EP 174 DI 10.1258/ar.2012.120045 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 190EI UT WOS:000322321400007 PM 23185071 ER PT J AU Kalra, MK Quick, P Singh, S Sandborg, M Persson, A AF Kalra, Mannudeep K. Quick, Petter Singh, Sarabjeet Sandborg, Michael Persson, Anders TI Whole spine CT for evaluation of scoliosis in children: feasibility of sub-milliSievert scanning protocol SO ACTA RADIOLOGICA LA English DT Article DE CT; scoliosis; radiation dose; automatic exposure control ID TUBE CURRENT MODULATION; COMPUTED-TOMOGRAPHY; DOSE REDUCTION; RECONSTRUCTION; OPTIMIZATION; STRATEGIES AB Background: Optimization of CT radiation dose is important for children due to their higher risk of radiation-induced adverse effects. Anatomical structures with high inherent contrast, such as bones can be imaged at very low radiation doses by optimizing scan parameters. Purpose: To assess feasibility of sub-milliSievert whole spine CT scanning protocol for evaluation of scoliosis in children. Material and Methods: With approval of the ethical board, we performed whole spine CT for evaluation of scoliosis in 22 children (age range, 3-18 years; mean age, 13 years; 13 girls, 9 boys) on a 128-slice dual source multidetector-row CT scanner. Lowest possible quality reference mAs value (image quality factor for xy-z automatic exposure control or xyz-AEC, CARE Dose 4D) was selected on a per patient basis. Remaining parameters were held constant at 3.0: 1 pitch, 128 x 0.6 mm detector collimation, 115.2 mm table feed per gantry rotation, 100 kVp, and 1 and 3 mm reconstructed sections. Average mAs, projected estimated dose savings with AEC, computed tomography dose index volume (CTDI vol), and dose length product (DLP) were recorded. Artifacts were graded on a four-point scale (1, no artifacts; 4, severe artifacts). Ability to identify vertebral and pedicular contours, and measure pedicular width and degree of vertebral rotation was graded on a three-point scale (1, unacceptable; 3, excellent). Results: All CT examinations were deemed as reliable for identifying vertebral and pedicular contours as well as for measuring pedicular width (5.9 +/- 1.6 mm) and degree of vertebral rotation (28.7 +/- 23.4 degrees). Mean objective image noise and signal to noise ratio (SNR) were 57.5 +/- 21.5 and 4.7 +/- 2.3, respectively. With a mean quality reference mAs of 13, the scanner employed an average actual effective mAs of 10 +/- 3.8 (range, 6-18 mAs) with an estimated radiation dose saving of 43.5 +/- 16.3% with xyz-AEC compared with fixed mAs. The mean CTDI, DLP, and estimated effective doses were 0.4 +/- 0.1 mGy (0.2-0.7 mGy), 21 +/- 10 mGy. cm (8-41 mGy. cm), and 0.3 +/- 0.1 mSv (0.12-0.64 mSv), respectively. Conclusion: Radiation dose for whole spine CT for evaluation of scoliosis in children can be minimized to less than one-third of a milliSievert while maintaining diagnostic image quality. C1 [Kalra, Mannudeep K.; Quick, Petter; Sandborg, Michael; Persson, Anders] Linkoping Univ, Linkoping Univ Hosp, Ctr Med Image Sci & Visualizat CMIV, Linkoping, Sweden. [Kalra, Mannudeep K.; Singh, Sarabjeet] Massachusetts Gen Hosp, Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. [Sandborg, Michael] Linkoping Univ Hosp, Dept Radiophys, S-58185 Linkoping, Sweden. RP Persson, A (reprint author), Linkoping Univ, Linkoping Univ Hosp, Ctr Med Image Sci & Visualizat CMIV, Linkoping, Sweden. EM anders.persson@cmiv.liu.se RI Persson, Anders/L-1004-2013 OI Persson, Anders/0000-0002-9446-6981 NR 14 TC 11 Z9 11 U1 0 U2 2 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD MAR PY 2013 VL 54 IS 2 BP 226 EP 230 DI 10.1258/ar.2012.110625 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 190EI UT WOS:000322321400015 PM 23138023 ER PT J AU Lopez, L DesRoches, CM Vogeli, C Grant, RW Iezzoni, LI Campbell, EG AF Lopez, Lenny DesRoches, Catherine M. Vogeli, Christine Grant, Richard W. Iezzoni, Lisa I. Campbell, Eric G. TI Characteristics of Primary Care Safety-Net Providers and Their Quality Improvement Attitudes and Activities: Results of a National Survey of Physician Professionalism SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE safety-net physicians; Medicaid; quality improvement; quality activities ID HEALTH-CARE; UNITED-STATES; ETHNIC DISPARITIES; MINORITY; REFORM; PARTICIPATION; MEDICAID; MASSACHUSETTS; INTERVENTIONS; SERVICES AB No current national data exist to characterize safety-net physicians and their attitudes toward and participation in quality improvement activities compared with non-safety-net physicians. The authors conducted a national random sample survey of internal medicine, family practice, and pediatrics primary care physicians (PCPs) and used weighted multivariable regression models to assess attitudes and participation in quality improvement activities. After multivariable adjustment, there were no significant differences in provider attitudes about or participation in quality improvement activities between safety-net and non-safety-net physicians. However, safety-net providers were almost twice as likely to look for racial/ethnic disparities in care within their practices and are as likely to be involved in quality improvement activities as non-safety-net providers; their attitudes are consistent with providing equitable and universal care. Increasing access by expanding Medicaid eligibility will require continued investment in the number and training of safety-net PCPs. C1 [Lopez, Lenny; Vogeli, Christine; Iezzoni, Lisa I.; Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [DesRoches, Catherine M.] Math Policy Res, Princeton, NJ USA. [Grant, Richard W.] Kaiser Permanente No Calif, Oakland, CA USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM llopez1@partners.org OI Grant, Richard/0000-0002-6164-8025 FU Institute on Medicine FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by a grant from the Institute on Medicine as a Profession to Eric Campbell, PhD, at the Mongan Institute for Health Policy at Massachusetts General Hospital. The Institute on Medicine as a Profession had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 48 TC 1 Z9 1 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR PY 2013 VL 28 IS 2 BP 151 EP 159 DI 10.1177/1062860612451048 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 194QV UT WOS:000322648700008 PM 23064095 ER PT J AU Bleier, BS Palmer, JN Cohen, NA AF Bleier, Benjamin S. Palmer, James N. Cohen, Noam A. TI Evaluation of a polysaccharide gel for laser-assisted skull base repair SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article; Proceedings Paper CT Combined Otolaryngological Spring Meeting of the Triologic-Society / 143rd Annual Meeting of the American-Otological-Society CY APR 28-MAY 02, 2010 CL Las Vegas, NV SP Amer Otol Soc, Triol Soc ID HUMAN-EXPERIENCE; TISSUE; RECONSTRUCTION; CLOSURE; MODEL AB Background: Endoscopic reconstruction of skull base defects remains a challenge. Laser tissue welding (LTW) is a technique in which a laser-activated solder is used to create instantaneous repairs of skull base defects with burst strengths far exceeding intracranial pressure (ICP). This study was designed to define the thermal and inflammatory profile of a novel polysaccharide soldering gel, to assess the burst strength of the repair, and to determine the time required for solder resorption. Methods: A prospective study was performed in rabbit and mouse models. Ten dorsal rabbit maxillary sinusotomies were laser welded and burst pressure thresholds were compared with control wounds on postoperative days (PODs) 0 and 5. All welds were examined histologically on PODs 0, 5, and 45 for thermal injury, inflammation, and degree of solder resorption. In mice, dura was exposed and laser welding was performed (n = 2). Results were compared histologically with dura exposed to laser energy alone (n = 2) on POD 7. Results: The burst pressures of the rabbit LTW group were significantly higher than control on PODs 0 (135.0 mmHg and SD = 5.8 versus 8.0 mmHg and SD = 0.5; n = 4) and 5 (155.4 mmHg and SD = 2.9 versus 41.7 mmHg and SD = 7.3; n = 4; p < 0.05). No significant thermal or inflammatory effect was found in any of the rabbit or mouse welds. Complete solder resorption was noted by POD 45. Conclusion: LTW using a polysaccharide gel is capable of creating mucosal repairs capable of withstanding over four times normal ICP without additional grafting materials. These repairs increase in strength over time, have no thermal or inflammatory sequelae, and establish complete solder resorption within 45 days. C1 [Bleier, Benjamin S.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Palmer, James N.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. RP Bleier, BS (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu OI Cohen, Noam/0000-0002-9462-3932 NR 10 TC 0 Z9 0 U1 1 U2 4 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2013 VL 27 IS 2 BP 148 EP 150 DI 10.2500/ajra.2013.27.3885 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 193GR UT WOS:000322547600018 PM 23562206 ER PT J AU Caplan, D Michaud, J Hufford, R AF Caplan, David Michaud, Jennifer Hufford, Rebecca TI Short-term memory, working memory, and syntactic comprehension in aphasia SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article DE Short-term memory; Working memory; Syntactic comprehension; Aphasia ID ONLINE SENTENCE COMPREHENSION; IMMEDIATE SERIAL-RECALL; MOVING-WINDOW TECHNIQUE; ALZHEIMERS-DISEASE; WORD-LENGTH; LANGUAGE COMPREHENSION; INDIVIDUAL-DIFFERENCES; RELATIVE CLAUSES; NEUROPSYCHOLOGICAL EVIDENCE; READING-COMPREHENSION AB Sixty-one people with aphasia were tested on 10 tests of short-term memory (STM) and for the ability to use syntactic structure to determine the meanings of 11 types of sentences in three tasksobject manipulation, picture matching, and picture matching with self-paced listening. Multilevel models showed relationships between measures of the ability to retain and manipulate item and order information in STM and accuracy and reaction time (RT), and a greater relationship between these STM measures and accuracy and RT for several more complex sentence types in individual tasks. There were no effects of measures of STM that reflect the use of phonological codes or rehearsal on comprehension. There was only one effect of STM measures on self-paced listening times. There were double dissociations between performance on STM and individual comprehension tasks, indicating that normal STM is not necessary to perform normally on these tasks. The results are most easily related to the view that STM plays a facilitatory role in supporting the use of the products of the comprehension process to accomplish operations related to tasks. C1 [Caplan, David; Michaud, Jennifer; Hufford, Rebecca] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Neuropsychol Lab, 175 Cambridge St,Suite 340,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD (National Institute on Deafness and Other Communication Disorders) [DC00942] FX This research was supported by NIDCD (National Institute on Deafness and Other Communication Disorders) Grant DC00942 to David Caplan. NR 127 TC 7 Z9 8 U1 7 U2 33 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0264-3294 EI 1464-0627 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD MAR 1 PY 2013 VL 30 IS 2 BP 77 EP 109 DI 10.1080/02643294.2013.803958 PG 33 WC Psychology; Psychology, Experimental SC Psychology GA 188RU UT WOS:000322212100002 PM 23865692 ER PT J AU Yang, X Pu, Y Hsieh, CL Ong, CA Psaltis, D Stankovic, KM AF Yang, Xin Pu, Ye Hsieh, Chia-Lung Ong, Cheng Ai Psaltis, Demetri Stankovic, Konstantina M. TI Two-photon microscopy of the mouse cochlea in situ for cellular diagnosis SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE two photon microscopy; cochlea; diagnosis; noise trauma ID INNER-EAR; FLUORESCENCE MICROSCOPY; ROUND WINDOW; BLOOD-FLOW; TISSUES; NERVE AB Sensorineural hearing loss is the most common type of hearing loss worldwide, yet the underlying cause is typically unknown because the inner ear cannot be biopsied today without destroying hearing, and intracochlear cells have not been imaged with resolution sufficient to establish diagnosis. Intracochlear imaging has been technologically challenging because of the cochlea's small size and encasement in bone. We report, for the first time, imaging of the mouse cochlea in situ without exogenous dyes, through a membranous round window, using a near-infrared femtosecond laser as the excitation and endogenous two-photon excitation fluorescence (TPEF) and second harmonic generation as the contrast mechanisms. We find that TPEF exhibits strong contrast allowing cellular, and even subcellular resolution, and detection of specific, noise-induced pathologic changes. Our results demonstrate that the round window provides a useful access to the cochlea through the middle ear, and they motivate future development of a new and efficient diagnostic tool based on two-photon micro-endoscopy. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Yang, Xin; Pu, Ye; Hsieh, Chia-Lung; Psaltis, Demetri] Ecole Polytech Fed Lausanne, Sch Engn, Opt Lab, CH-1015 Lausanne, Switzerland. [Hsieh, Chia-Lung] CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA. [Ong, Cheng Ai; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Ong, Cheng Ai; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM konstantina_stankovic@meei.harvard.edu RI Hsieh, Chia-Lung/C-8544-2013 OI Hsieh, Chia-Lung/0000-0002-6757-8689 FU Bertarelli Foundation FX We are grateful for the support of the Bertarelli Foundation. NR 29 TC 6 Z9 6 U1 0 U2 9 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR PY 2013 VL 18 IS 3 AR 031104 DI 10.1117/1.JBO.18.3.031104 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 190JV UT WOS:000322336700008 PM 23165736 ER PT J AU Mechanick, JI Youdim, A Jones, DB Garvey, WT Hurley, DL McMahon, MM Heinberg, LJ Kushner, R Adams, TD Shikora, S Dixon, JB Brethauer, S AF Mechanick, Jeffrey I. Youdim, Adrienne Jones, Daniel B. Garvey, W. Timothy Hurley, Daniel L. McMahon, M. Molly Heinberg, Leslie J. Kushner, Robert Adams, Ted D. Shikora, Scott Dixon, John B. Brethauer, Stacy TI Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient-2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery SO OBESITY LA English DT Article DE Bariatric surgery; Obesity; Metabolic surgery; Diabetes surgery; Metabolic syndrome; Clinical practice guidelines; Best practice guidelines; Weight loss surgery ID Y-GASTRIC-BYPASS; LAPAROSCOPIC-SLEEVE-GASTRECTOMY; TYPE-2 DIABETES-MELLITUS; WEIGHT-LOSS SURGERY; BODY-MASS INDEX; PROSPECTIVE-RANDOMIZED-TRIAL; OF-THE-LITERATURE; OUTCOMES LONGITUDINAL DATABASE; HELICOBACTER-PYLORI INFECTION; CARDIOVASCULAR RISK-FACTORS AB The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE-TOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues. C1 [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, New York, NY USA. [Youdim, Adrienne] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Jones, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Birmingham VA Med Ctr, AACE, Birmingham, AL USA. [Hurley, Daniel L.; McMahon, M. Molly] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, AACE, Rochester, MN USA. [Heinberg, Leslie J.] Cleveland Clin, Lerner Coll Med, BMI Director Behav Serv, TOS, Cleveland, OH 44106 USA. [Kushner, Robert] Northwestern Univ, Feinberg Sch Med, TOS, Chicago, IL 60611 USA. [Adams, Ted D.] Univ Utah, Sch Med, TOS, Hlth & Fitness Inst,Intermt Healthcare & Cardiova, Salt Lake City, UT USA. [Shikora, Scott] Harvard Univ, Brigham & Womens Hosp, Sch Med, ASMBS,Ctr Metab Hlth & Bariatr Surg, Boston, MA 02115 USA. [Dixon, John B.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Brethauer, Stacy] Cleveland Clin, Bariatr & Metab Inst, Cleveland Clin Lerner Coll Med, Cleveland, OH 44106 USA. RP Mechanick, JI (reprint author), Icahn Sch Med Mt Sinai, New York, NY USA. EM jeffreymechanick@gmail.com RI Dixon, John/A-5318-2011 OI Dixon, John/0000-0001-5391-4082 FU NIDDK NIH HHS [P30 DK079626] NR 395 TC 183 Z9 189 U1 7 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD MAR PY 2013 VL 21 SU 1 BP S1 EP S27 DI 10.1002/oby.20461 PG 27 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187TB UT WOS:000322141500001 PM 23529939 ER PT J AU Baylor, A Muzoora, C Bwana, M Kembabazi, A Haberer, JE Matthews, LT Tsai, AC Hunt, PW Martin, JN Bangsberg, DR AF Baylor, Anna Muzoora, Conrad Bwana, Mwebsa Kembabazi, Annet Haberer, Jessica E. Matthews, Lynn T. Tsai, Alexander C. Hunt, Peter W. Martin, Jeffrey N. Bangsberg, David R. TI Dissemination of Research Findings to Research Participants Living with HIV in Rural Uganda: Challenges and Rewards SO PLOS MEDICINE LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY; FOOD INSECURITY; INDIVIDUALS; HIV/AIDS C1 [Baylor, Anna; Haberer, Jessica E.; Matthews, Lynn T.; Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Baylor, Anna; Muzoora, Conrad; Bwana, Mwebsa; Kembabazi, Annet; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Haberer, Jessica E.; Matthews, Lynn T.; Tsai, Alexander C.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Hunt, Peter W.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. RP Baylor, A (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM dbangsberg@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU NIAID NIH HHS [P30 AI027763, P30 AI060354]; NIMH NIH HHS [K24 MH-87227, K-24 MH87227, K23 MH-087228, K23 MH-096620, K23 MH087228, K23 MH095655, K23 MH096620, R0-1 MH-54907, R01 MH054907] NR 18 TC 3 Z9 3 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAR PY 2013 VL 10 IS 3 AR e1001397 DI 10.1371/journal.pmed.1001397 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 115GM UT WOS:000316800600002 PM 23472055 ER PT J AU Ayash, CR Simon, SR Marshall, R Kasper, J Chomitz, V Hacker, K Kleinman, KP Taveras, EM AF Ayash, Christine R. Simon, Steven R. Marshall, Richard Kasper, Jill Chomitz, Virginia Hacker, Karen Kleinman, Ken P. Taveras, Elsie M. TI Evaluating the Impact of Point-of-Care Decision Support Tools in Improving Diagnosis of Obese Children in Primary Care SO OBESITY LA English DT Article ID HEALTH INFORMATION-TECHNOLOGY; PEDIATRIC NURSE PRACTITIONERS; ELECTRONIC MEDICAL-RECORD; BODY-MASS INDEX; ADOLESCENT OBESITY; REGISTERED DIETITIANS; OVERWEIGHT CHILDREN; CHILDHOOD OBESITY; US CHILDREN; MANAGEMENT AB Objective: The purpose of this quasi-experimental study was to examine the effect of a computerized point-of-care alert with clinical decision support on the rates of diagnosis of childhood obesity in a multisite group practice in Massachusetts; Cambridge Health Alliance (CHA) which implemented an alert, relative to a separate group practice, Harvard Vanguard Medical Associates (HVMA), that did not. Design and Methods: Height and weight data from 19,466 children of 2-18 years with 34,908 well-child care visits in CHA and 123,446 children with 282,271 visits in HVMA between 2006 and 2008 were collected. The alert and decision support tool was activated for CHA patients with an age-and sex-specific body mass index of >= 95th percentile. The main outcome measure was documentation of an International Classification of Diseases, Ninth Revision [ICD-9] code for obesity before and after implementation of the alert at CHA in 2007. Results: Among obese children, the adjusted rate of an ICD-9 diagnosis of obesity increased from 20062007 to 2008 significantly more at CHA than at HVMA (P < 0.001 for time-by-provider group interaction). In 2006-2007, the rate of ICD-9 diagnosis of obesity was significantly lower at CHA than at HVMA (adjusted odds ratio [OR]: 0.57; 95% confidence interval [CI]: 0.52-0.62); but by 2008 was significantly higher at CHA than HVMA (adjusted OR: 1.25; 95% CI: 1.14-1.38). Conclusion: A point-of-care alert was effective in improving obesity diagnosis in a multisite group practice, relative to a separate group practice that did not adopt an alert. Clinical decision support tools could help improve obesity diagnosis in pediatric primary care. C1 [Ayash, Christine R.; Kleinman, Ken P.] Harvard Univ, Sch Med, Obes Prevent Program, Dept Populat Med, Boston, MA 02115 USA. [Ayash, Christine R.; Kleinman, Ken P.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Simon, Steven R.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Gen Internal Med Sect, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Marshall, Richard] Harvard Vanguard Med Associates, Dept Pediat, Boston, MA USA. [Kasper, Jill] Cambridge Hlth Alliance, Dept Pediat, Cambridge, MA USA. [Chomitz, Virginia; Hacker, Karen] Cambridge Hlth Alliance, Inst Community Hlth, Cambridge, MA USA. [Chomitz, Virginia] Harvard Univ, Sch Med, Inst Community Hlth, Boston, MA USA. [Taveras, Elsie M.] Harvard Univ, Dept Ambulatory Care & Prevent, Sch Med, Bosto, MA USA. RP Ayash, CR (reprint author), Harvard Univ, Sch Med, Obes Prevent Program, Dept Populat Med, Boston, MA 02115 USA. EM Christine_ayash@harvardpilgrim.org FU American Diabetes Association [1-09-CR-49]; American Recovery and Reinvestment Act [R18 AE000026] FX This research was supported in part by grants from The American Diabetes Association (Award #1-09-CR-49) and The American Recovery and Reinvestment Act (Award #R18 AE000026). NR 34 TC 4 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD MAR PY 2013 VL 21 IS 3 BP 576 EP 582 DI 10.1002/oby.20161 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AK UT WOS:000322087600048 PM 23592666 ER PT J AU Lima, MMO Pareja, JC Alegre, SM Geloneze, SR Kahn, SE Astiarraga, BD Chaim, EA Baracat, J Geloneze, B AF Lima, Marcelo M. O. Pareja, Jose C. Alegre, Sarah M. Geloneze, Sylka R. Kahn, Steven E. Astiarraga, Brenno D. Chaim, Elinton A. Baracat, Jamal Geloneze, Bruno TI Visceral Fat Resection in Humans: Effect on Insulin Sensitivity, Beta-Cell Function, Adipokines, and Inflammatory Markers SO OBESITY LA English DT Article ID TYPE-2 DIABETES-MELLITUS; Y GASTRIC BYPASS; METABOLIC SYNDROME; SURGICAL REMOVAL; OBESE-PATIENTS; RESISTANCE; OMENTECTOMY; PATHOGENESIS; ADIPOSITY; RISK AB Objective: The visceral fat is linked to insulin resistance, the metabolic syndrome, type 2 diabetes and an increased cardiovascular risk, but it is not clear whether it has a causative role. Design and Methods: Surgical resection of this fat depot is a research model to address this issue. Twenty premenopausal women with metabolic syndrome and grade III obesity were randomized to undergo Roux-en-Y gastric bypass (RYGBP) either alone or combined with omentectomy. Insulin sensitivity (IS; euglycemic-hyperinsulinemic clamp), acute insulin response to glucose (AIR; intravenous glucose tolerance test), disposition index (DI = AIR x IS measured by clamp), lipid profile, adipokine profile (leptin, adiponectin, resistin, visfatin, interleukin-6, TNF-alpha, MCP-1), ultra-sensitive C-reactive protein (CRP), body composition, and abdominal fat echography were assessed prior to surgery and 1, 6, and 12 months post-surgery. Results: Omentectomy was associated with greater weight loss at all time points. IS improved similarly in both groups. Omentectomy was associated to lower CRP after 12 months, but it did not influence adipokines and other metabolic parameters. Among non-diabetic subjects, omentectomy was associated with a preservation of baseline AIR after 12 months (as opposed to deterioration in the control group) and a greater DI after 6 and 12 months. Conclusion: Although omentectomy did not enhance the effect of RYGBP on insulin sensitivity and adipokines, it was associated with a preservation of insulin secretion, a greater weight loss, and lower CRP. C1 [Lima, Marcelo M. O.; Pareja, Jose C.; Geloneze, Sylka R.; Astiarraga, Brenno D.; Geloneze, Bruno] State Univ Campinas UNICAMP, Lab Invest Metab & Diabet LIMED Gastrocent, Campinas, SP, Brazil. [Pareja, Jose C.; Chaim, Elinton A.] State Univ Campinas UNICAMP, Dept Surg, Campinas, SP, Brazil. [Alegre, Sarah M.; Astiarraga, Brenno D.] State Univ Campinas UNICAMP, Dept Internal Med, Campinas, SP, Brazil. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Baracat, Jamal] State Univ Campinas UNICAMP, Dept Radiol, Campinas, SP, Brazil. RP Lima, MMO (reprint author), State Univ Campinas UNICAMP, Lab Invest Metab & Diabet LIMED Gastrocent, Campinas, SP, Brazil. EM endo.marcelolima@gmail.com OI Kahn, Steven/0000-0001-7307-9002 FU Fundacao de Apoio a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, Brazil [05/58627-2]; US Department of Veterans Affairs FX Funding agencies: This study was funded by Fundacao de Apoio a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, Brazil (Protocol 05/58627-2) and supported in part by funding from the US Department of Veterans Affairs. NR 25 TC 11 Z9 12 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD MAR PY 2013 VL 21 IS 3 BP E182 EP E189 DI 10.1002/oby.20030 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 187AK UT WOS:000322087600002 PM 23404948 ER PT J AU Yuan, YD Andronesi, OC Bortfeld, TR Richter, C Wolf, R Guimaraes, AR Hong, TS Seco, J AF Yuan, Yading Andronesi, Ovidiu C. Bortfeld, Thomas R. Richter, Christian Wolf, Russell Guimaraes, Alexander R. Hong, Theodore S. Seco, Joao TI Feasibility study of in vivo MRI based dosimetric verification of proton end-of-range for liver cancer patients SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Proton therapy; Liver tumor; Radiation effects on liver; Magnetic resonance imaging; In vivo dosimetry; Distal proton range verification ID ENHANCED MRI; THERAPY; TOLERANCE AB Purpose: To investigate the feasibility of using MRI to verify proton beam distal range for liver tumor treatment in a retrospective study. Methods and materials: Because the follow-up hepatocyte-specific functional MR imaging can detect the radiobiological change of liver tissue after radiation, we firstly registered the contrast-enhanced MR images to the planning CT images from 5 liver patients, then overlaid the prescribed dose distribution on the MR images. Since dose calculation is most accurate at the penumbra dose region, we correlated the MR signal intensity (SI) to the radiation dose at the superior/inferior penumbra region. This dose-SI correlation was finally employed on registered MR images to estimate the proton end-of-range. Results: Statistically significant correlations between radiation dose and MR SI were observed in superior/inferior penumbra regions, with correlation coefficient ranging from 0.93 to 0.99. By applying the dose-SI correlation to the distal region of each proton beam, the mean difference between MR-estimated and the planned dose range was -2.18 +/- 4.89 mm for anterior-posterior beams and -3.90 +/- 5.87 mm for lateral beams. Conclusions: This feasibility study proved the principle that proton dose range can be verified in vivo by follow-up MR images after proton liver treatment. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Yuan, Yading; Bortfeld, Thomas R.; Richter, Christian; Wolf, Russell; Hong, Theodore S.; Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yuan, Yading] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yuan, YD (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX 315, Boston, MA 02114 USA. EM yyuan3@partners.org FU Federal Share of program income earned by Massachusetts General Hospital [CA059267]; Proton Therapy Research and Treatment Center FX The authors are grateful to Dr. Gregory C, Sharp for helpful discussion on image registration. They also thank Dr. Peter Biggs for his insightful comments on this study. This study was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06-CA059267, Proton Therapy Research and Treatment Center. NR 17 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAR PY 2013 VL 106 IS 3 BP 378 EP 382 DI 10.1016/j.radonc.2013.01.016 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 189VG UT WOS:000322295800020 PM 23473960 ER PT J AU Zhou, AY Shen, RR Kim, E Lock, YJ Xu, M Chen, ZJJ Hahn, WC AF Zhou, Alicia Y. Shen, Rhine R. Kim, Eejung Lock, Ying J. Xu, Ming Chen, Zhijian J. Hahn, William C. TI IKK epsilon-Mediated Tumorigenesis Requires K63-Linked Polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 Ubiquitin Ligase Complex SO CELL REPORTS LA English DT Article ID NF-KAPPA-B; BREAST-CANCER ONCOGENE; TUMOR-SUPPRESSOR CYLD; KINASE EPSILON; ACTIVATION; PATHWAYS; TBK1; PHOSPHORYLATION; IKBKE; TANK AB I kappa B kinase epsilon (IKK epsilon, IKBKE) is a key regulator of innate immunity and a breast cancer oncogene, amplified in similar to 30% of breast cancers, that promotes malignant transformation through NF-kappa B activation. Here, we show that IKK epsilon is modified and regulated by K63-linked polyubiquitination at lysine 30 and lysine 401. Tumor necrosis factor alpha and interleukin-1 beta stimulation induces IKK epsilon K63-linked polyubiquitination over baseline levels in both macrophages and breast cancer cell lines, and this modification is essential for IKK epsilon kinase activity, IKK epsilon-mediated NF-kappa B activation, and IKK epsilon-induced malignant transformation. Disruption of K63-linked ubiquitination of IKK epsilon does not affect its overall structure but impairs the recruitment of canonical NF-kappa B proteins. A cIAP1/cIAP2/TRAF2 E3 ligase complex binds to and ubiquitinates IKK epsilon. Altogether, these observations demonstrate that K63-linked polyubiquitination regulates IKK epsilon activity in both inflammatory and oncogenic contexts and suggests an alternative approach to targeting this breast cancer oncogene. C1 [Zhou, Alicia Y.; Shen, Rhine R.; Kim, Eejung; Lock, Ying J.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhou, Alicia Y.; Shen, Rhine R.; Kim, Eejung; Lock, Ying J.; Hahn, William C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Zhou, Alicia Y.; Shen, Rhine R.; Kim, Eejung; Lock, Ying J.; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Xu, Ming; Chen, Zhijian J.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Chen, Zhijian J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu FU National Institutes of Health/National Cancer Institute grant [R01 CA130988]; Department of Defense Breast Cancer Research Program Predoctoral Traineeship Award [W81XWH-08-1-0763] FX We thank J. Wade Harper and members of the Hahn and Cichowski labs for thoughtful discussion, reagents, and technical assistance. W.C.H. is a consultant for Novartis Pharmaceuticals. This work was supported in part by National Institutes of Health/National Cancer Institute grant R01 CA130988 (W.C.H.) and Department of Defense Breast Cancer Research Program Predoctoral Traineeship Award W81XWH-08-1-0763 (A.Y.Z.). NR 40 TC 16 Z9 22 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAR PY 2013 VL 3 IS 3 BP 724 EP 733 DI 10.1016/j.celrep.2013.01.031 PG 10 WC Cell Biology SC Cell Biology GA 184MZ UT WOS:000321896000017 PM 23453969 ER PT J AU Tu, DQ Zhu, ZH Zhou, AY Yun, CH Lee, KE Toms, AV Li, YQ Dunn, GP Chan, E Thai, T Yang, SH Ficarro, SB Marto, JA Jeon, H Hahn, WC Barbie, DA Eck, MJ AF Tu, Daqi Zhu, Zehua Zhou, Alicia Y. Yun, Cai-hong Lee, Kyung-Eun Toms, Angela V. Li, Yiqun Dunn, Gavin P. Chan, Edmond Tran Thai Yang, Shenghong Ficarro, Scott B. Marto, Jarrod A. Jeon, Hyesung Hahn, William C. Barbie, David A. Eck, Michael J. TI Structure and Ubiquitination-Dependent Activation of TANK-Binding Kinase 1 SO CELL REPORTS LA English DT Article ID NF-KAPPA-B; INNATE IMMUNE-RESPONSE; BREAST-CANCER ONCOGENE; TUMOR-SUPPRESSOR CYLD; IKK-RELATED KINASE; CELL-TRANSFORMATION; LIVER DEGENERATION; I INTERFERON; CROSS-TALK; TBK1 AB Upon stimulation by pathogen-associated inflammatory signals, TANK-binding kinase 1 (TBK1) induces type I interferon expression and modulates nuclear factor kappa B (NF-kappa B) signaling. Here, we describe the 2.4 angstrom-resolution crystal structure of nearly full-length TBK1 in complex with specific inhibitors. The structure reveals a dimeric assembly created by an extensive network of interactions among the kinase, ubiquitin-like, and scaffold/dimerization domains. An intact TBK1 dimer undergoes K63-linked polyubiquitination on lysines 30 and 401, and these modifications are required for TBK1 activity. The ubiquitination sites and dimer contacts are conserved in the close homolog inhibitor of kB kinase epsilon (IKK epsilon) but not in IKK beta, a canonical IKK that assembles in an unrelated manner. The multidomain architecture of TBK1 provides a structural platform for integrating ubiquitination with kinase activation and IRF3 phosphorylation. The structure of TBK1 will facilitate studies of the atypical IKKs in normal and disease physiology and further the development of more specific inhibitors that may be useful as anticancer or anti-inflammatory agents. C1 [Tu, Daqi; Yun, Cai-hong; Toms, Angela V.; Li, Yiqun; Ficarro, Scott B.; Marto, Jarrod A.; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Zhu, Zehua; Zhou, Alicia Y.; Dunn, Gavin P.; Chan, Edmond; Tran Thai; Yang, Shenghong; Hahn, William C.; Barbie, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tu, Daqi; Yun, Cai-hong; Toms, Angela V.; Ficarro, Scott B.; Marto, Jarrod A.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhu, Zehua; Zhou, Alicia Y.; Dunn, Gavin P.; Chan, Edmond; Tran Thai; Yang, Shenghong; Hahn, William C.; Barbie, David A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Lee, Kyung-Eun; Jeon, Hyesung] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul 130650, South Korea. RP Barbie, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM dbarbie@partners.org; eck@red.dfci.harvard.edu FU NIH [PO1 CA154303, R01 CA130988, P01 CA117969, K08 CA13891801-A1, RO1 GM071834, RO1 CA080942]; Korea Institute of Science and Technology; V Foundation for Cancer Research FX We thank Dr. Natalia Shapiro and Sir Philip Cohen (MRC Protein Phosphorylation Unit, University of Dundee, Scotland, UK) for synthesizing and sharing the MRT67307 used in this study. We thank Nathanael Gray for helpful discussions, and the staff of the NE-CAT beamline at the Advanced Photon Source, Argonne National Laboratory, for assistance with data collection and processing. This work was supported in part by NIH grants PO1 CA154303 (M.J.E. and W.C.H.), R01 CA130988 (W.C.H.), P01 CA117969 (W.C.H.), K08 CA13891801-A1 (D.A.B.), RO1 GM071834 (M.J.E.), and RO1 CA080942 (M.J.E.). H.J. acknowledges support from the intramural research program of the Korea Institute of Science and Technology. D.A.B. was supported by a V Scholar Grant from the V Foundation for Cancer Research. W.C.H. and M.J.E. are consultants for Novartis Pharmaceuticals. NR 52 TC 46 Z9 48 U1 4 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAR PY 2013 VL 3 IS 3 BP 747 EP 758 DI 10.1016/j.celrep.2013.01.033 PG 12 WC Cell Biology SC Cell Biology GA 184MZ UT WOS:000321896000019 PM 23453972 ER PT J AU El Ouaamari, A Kawamori, D Dirice, E Liew, CW Shadrach, JL Hu, J Katsuta, H Hollister-Lock, J Qian, WJ Wagers, AJ Kulkarni, RN AF El Ouaamari, Abdelfattah Kawamori, Dan Dirice, Ercument Liew, Chong Wee Shadrach, Jennifer L. Hu, Jiang Katsuta, Hitoshi Hollister-Lock, Jennifer Qian, Wei-Jun Wagers, Amy J. Kulkarni, Rohit N. TI Liver-Derived Systemic Factors Drive beta Cell Hyperplasia in Insulin-Resistant States (vol 3, pg 401, 2013) SO CELL REPORTS LA English DT Correction C1 [El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Wagers, Amy J.; Kulkarni, Rohit N.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. [Katsuta, Hitoshi; Hollister-Lock, Jennifer] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. [Katsuta, Hitoshi; Hollister-Lock, Jennifer] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Qian, Wei-Jun] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Qian, Wei-Jun] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. EM rohit.kulkarni@joslin.harvard.edu RI Dirice, Ercument/B-2825-2017 NR 1 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAR PY 2013 VL 3 IS 3 BP 968 EP 968 DI 10.1016/j.celrep.2013.03.021 PG 1 WC Cell Biology SC Cell Biology GA 184MZ UT WOS:000321896000038 ER PT J AU Clarke, JC Aragam, JR Bhatt, DL Brown, JD Ferrazzani, S Pietro, DA Maron, BA AF Clarke, Jonathan C. Aragam, Jayashri R. Bhatt, Deepak L. Brown, Jonathan D. Ferrazzani, Sarah Pietro, Daniel A. Maron, Bradley A. TI An Unusual Cause of Dyspnea Diagnosed Late in Life Severe Pulmonary Hypertension Resulting From Isolated Anomalous Pulmonary Venous Connection SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE anomalous pulmonary vein; congenital heart disease; pulmonary hypertension C1 [Clarke, Jonathan C.; Aragam, Jayashri R.; Bhatt, Deepak L.; Brown, Jonathan D.; Ferrazzani, Sarah; Pietro, Daniel A.; Maron, Bradley A.] Vet Affairs Boston Healthcare Syst, Dept Cardiol, Boston, MA USA. [Clarke, Jonathan C.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Clarke, Jonathan C.; Aragam, Jayashri R.; Bhatt, Deepak L.; Brown, Jonathan D.; Maron, Bradley A.] Harvard Univ, Sch Med, Boston, MA USA. [Aragam, Jayashri R.; Bhatt, Deepak L.; Brown, Jonathan D.; Maron, Bradley A.] Brigham & Womens Hosp, Dept Internal Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Maron, BA (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, PBB-1,75 Francis St, Boston, MA 02115 USA. EM bmaron@partners.org FU American Heart Association [11POST6720000]; Lerner Foundation at Brigham and Women's Hospital; Gilead Young Investigator Research Grant; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company FX This work was supported in part by the American Heart Association (11POST6720000) and the Lerner Foundation at Brigham and Women's Hospital (Dr Maron).; Dr Maron is a recipient of the Gilead Young Investigator Research Grant. Dr Bhatt has served on the advisory board for Medscape Cardiology; on the board of directors for Boston VA Research Institute and Society of Chest Pain Centers; and as chair of the American Heart Association Get With The Guidelines Science Subcommittee. Dr Bhatt has received honoraria from the American College of Cardiology (editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (chief medical editor, Cardiology Today Intervention), WebMD (CME steering committees). Dr Ghatt has been senior associate editor, Journal of Invasive Cardiology and has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. Dr Bhatt has performed unfunded research for FlowCo, PLx Pharma, and Takeda. The other authors have no conflicts to report. NR 4 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAR PY 2013 VL 6 IS 2 BP 349 EP 351 DI 10.1161/CIRCIMAGING.112.000145 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 167XM UT WOS:000320668800028 PM 23512781 ER PT J AU Wada, K Gerbaudo, VH Spector, M AF Wada, Keisuke Gerbaudo, Victor H. Spector, Myron TI Effects of PDGF-BB and OP-1 on Mesenchymal Stem Cells in a Porous Mineral Block SO INTERNATIONAL JOURNAL OF PERIODONTICS & RESTORATIVE DENTISTRY LA English DT Article ID ANORGANIC BOVINE BONE; VERTICAL RIDGE AUGMENTATION; GROWTH FACTOR-BB; OSTEOBLASTS; MATRIX; MODEL AB The aim of this study was to evaluate the effects of an osteogenic medium supplemented with platelet-derived growth factor (PDGF) BB and osteogenic protein (OP) 1 on the proliferation and differentiation of mesenchymal stem cells (MSCs) in an anorganic bovine cancellous bone scaffold. At day 7, there was a statistically significant increase in the number of cells in the scaffolds in the group treated with the medium supplemented with both PDGF-BB and OP-1 when compared with the control groups. The highest alkaline phosphate levels, at 14 and 21 days, were recorded for the samples in medium supplemented with OP-1 alone reflecting osteogenic differentiation. The results commend OP-1, as well as PDGF-BB, for incorporation into porous mineral scaffolds for vertical ridge augmentation. C1 [Wada, Keisuke; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Wada, Keisuke] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Wada, Keisuke] Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA. [Gerbaudo, Victor H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Gerbaudo, Victor H.] Brigham & Womens Hosp, Dept Radiol, Nucl Med & Mol Imaging Program, Boston, MA 02115 USA. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu NR 20 TC 2 Z9 2 U1 0 U2 5 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0198-7569 J9 INT J PERIODONT REST JI Int. J. Periodontics Restor. Dent. PD MAR-APR PY 2013 VL 33 IS 2 BP E72 EP E78 DI 10.11607/prd.1670 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 185WP UT WOS:000322001400005 PM 23484183 ER PT J AU Ravven, S Bader, C Azar, A Rudolph, JL AF Ravven, Simha Bader, Caroline Azar, Armin Rudolph, James L. TI Depressive Symptoms After CABG Surgery: A Meta-analysis SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE cardiac surgery; coronary artery bypass graft surgery; depression ID CORONARY-ARTERY-BYPASS; QUALITY-OF-LIFE; GRAFT-SURGERY; RANDOMIZED-TRIAL; NEUROCOGNITIVE FUNCTION; COGNITIVE DECLINE; CARDIAC-SURGERY; RISK-FACTOR; ANXIETY; HEALTH AB Learning Objectives: After participating in this educational activity, the reader should be better able to measure the risk of depression before and after coronary artery bypass graft (CABG) surgery; examine the course of depression after CABG; and apply the results of the study to the treatment of patients. Objective: Depression is highly comorbid with coronary artery disease. Clinicians face the question of whether patients' depressive symptoms will improve after coronary artery bypass graft surgery (CABG). The objective of this meta-analysis is to determine the course of depressive symptoms after CABG. Methods: EMBASE, PubMed, and PsycINFO were searched for studies assessing depression before and after CABG. Meta-analyses were performed for depression at early (1-2 weeks), recovery (>2 weeks to 2 months), mid (>2 months to 6 months), and late (>6 months) postoperative time points. Heterogeneity and publication bias were analyzed. Results: Thirty-nine studies were included in the meta-analysis. Twelve reported dichotomous outcomes; 18 reported continuous outcomes; and 9 reported both. Risk of depression was increased early (relative risk [RR] = 1.27; 95% confidence interval [CI], 1.01-1.61). There was a significantly decreased risk of depression at recovery (RR = 0.78; 95% CI, 0.67-0.90), mid (RR = 0.64; 95% CI, 0.58-0.70), and late (RR = 0.68; 95% CI, 0.58-0.79) time points without heterogeneity. All studies reporting continuous depression scales had significant heterogeneity. Conclusions: The risk of depression decreased post-CABG when depression was measured dichotomously. While depression improves overall and remits for some patients after CABG, the majority of patients will not experience remission of depression. Preoperative and postoperative depression monitoring is important. C1 [Ravven, Simha] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ravven, Simha] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, England. [Bader, Caroline] Albert Einstein Coll Med, New York, NY USA. [Azar, Armin] Providence VA Med Ctr, Providence, RI USA. [Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Rudolph, JL (reprint author), 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU American Federation for Aging Research; Boston MSTAR; National Institute of Health [AG038027-01]; Harvard Medical School Kaplan Depression Fellowship; VA Rehabilitation Career Development Award FX Supported by American Federation for Aging Research, Boston MSTAR, and National Institute of Health (grant no. AG038027-01) (Ms. Bader and Dr. Rudolph); a Harvard Medical School Kaplan Depression Fellowship (Dr. Azar); and a VA Rehabilitation Career Development Award (Dr. Rudolph). NR 51 TC 13 Z9 13 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2013 VL 21 IS 2 BP 59 EP 69 DI 10.1097/HRP.0b013e31828a3612 PG 11 WC Psychiatry SC Psychiatry GA 173RZ UT WOS:000321097900001 PM 23656830 ER PT J AU Uchida, M Schmertz, SK Miller, M Yeung, A AF Uchida, Mai Schmertz, Stefan K. Miller, Martin Yeung, Albert TI A Vietnam War Veteran with Posttraumatic Stress Disorder, Status-Post-Myocardial Infarction, in Therapy with an Asian Therapist SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE cross-cultural; posttraumatic stress disorder; psychotherapy; veteran; Vietnam War ID OUTCOMES C1 [Uchida, Mai; Schmertz, Stefan K.; Miller, Martin; Yeung, Albert] Harvard Univ, Sch Med, Boston, MA USA. [Uchida, Mai; Schmertz, Stefan K.; Miller, Martin; Yeung, Albert] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Miller, Martin] Boston Psychoanalyt Soc & Inst Inc, Child Analyt Program, Boston, MA USA. [Miller, Martin] Psychoanalyt Inst New England, Boston, MA USA. RP Uchida, M (reprint author), Yawkey 6A,55 Fruit St, Boston, MA 02114 USA. EM muchida@partners.org NR 11 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2013 VL 21 IS 2 BP 92 EP 101 DI 10.1097/HRP.0b013e318283bfa2 PG 10 WC Psychiatry SC Psychiatry GA 173RZ UT WOS:000321097900003 PM 23656832 ER PT J AU Rahimy, E Sarraf, D AF Rahimy, Ehsan Sarraf, David TI Cystoid Macular Edema Secondary to Nanoparticle Albumin-Bound Paclitaxel Therapy SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID MACULOPATHY AB The authors report a case of nanoparticle albumin-bound paclitaxel-induced cystoid macular edema (CME) without fluorescein angiographic leakage in a patient being treated for metastatic breast cancer. The CME briskly improved 3 weeks after the chemotherapeutic agent was discontinued and was completely resolved after 6 weeks. Patients receiving taxane therapy must be counseled to report any vision problems during their treatment period because early recognition of this rare but severe adverse event can facilitate appropriate intervention to reverse visual compromise and minimize any potential long-term ophthalmologic sequelae. C1 [Rahimy, Ehsan; Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Sarraf, David] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu FU Karl Kirchgessner Foundation at the Jules Stein Eye Institute FX Supported by a grant from the Karl Kirchgessner Foundation at the Jules Stein Eye Institute. NR 9 TC 5 Z9 5 U1 1 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAR-APR PY 2013 VL 44 IS 2 BP 187 EP 189 DI 10.3928/23258160-20130212-02 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 172PS UT WOS:000321017200015 PM 23421925 ER PT J AU Yonekawa, Y Shildkrot, Y Eliott, D AF Yonekawa, Yoshihiro Shildkrot, Yevgeniy Eliott, Dean TI Inferior Peripheral Nonperfusion in Bilateral Diffuse Uveal Melanocytic Proliferation SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID SICKLE-CELL TRAIT; RETINOPATHY AB Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic syndrome characterized by cataract, photoreceptor loss and subretinal fluid overlying patchy areas of retinal pigment epithelium atrophy, and a diffusely thickened choroid with focal nodules. We present the case of a 64-year-old woman with a history of endometrial adenocarcinoma who developed BDUMP with bilateral exudative retinal detachments with inferior peripheral retinal ischemia. This new finding of peripheral nonperfusion expands the spectrum of BDUMP. C1 [Yonekawa, Yoshihiro; Shildkrot, Yevgeniy; Eliott, Dean] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Eliott, D (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 11 TC 2 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 EI 1938-2375 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAR-APR PY 2013 VL 44 IS 2 BP 190 EP 192 DI 10.3928/23258160-20130313-11 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 172PS UT WOS:000321017200016 PM 23510044 ER PT J AU Sembajwe, G Tveito, TH Hopcia, K Kenwood, C O'Day, ET Stoddard, AM Dennerlein, JT Hashimoto, D Sorensen, G AF Sembajwe, Grace Tveito, Torill Helene Hopcia, Karen Kenwood, Christopher O'Day, Elizabeth Tucker Stoddard, Anne M. Dennerlein, Jack T. Hashimoto, Dean Sorensen, Glorian TI Psychosocial Stress and Multi-site Musculoskeletal Pain A Cross-sectional Survey of Patient Care Workers SO WORKPLACE HEALTH & SAFETY LA English DT Article ID JOB CONTENT QUESTIONNAIRE; LOW-BACK-PAIN; SUBJECTIVE HEALTH COMPLAINTS; MANUAL HANDLING ACTIVITIES; UPPER EXTREMITY DISORDERS; RISK-FACTORS; HOSPITAL NURSES; NURSING PERSONNEL; PSYCHOMETRIC PROPERTIES; PROSPECTIVE COHORT AB The aim of this study was to assess the relationship between psychosocial factors at work and multi-site musculoskeletal pain among patient care workers. In a survey of 1,572 workers from two hospitals, occupational psychosocial factors and health outcomes of workers with single and multi-site pain were evaluated using items from the Job Content Questionnaire that was designed to measure psychological demands, decision latitude, and social support. An adapted Nordic Questionnaire provided data on the musculoskeletal pain outcome. Covariates included body mass index, age, gender, and occupation. The analyses revealed statistically significant associations between psychosocial demands and multi-site musculoskeletal pain among patient care associates, nurses, and administrative personnel, both men and women. Supervisor support played a significant role for nurses and women. These results remained statistically significant after adjusting for covariates. These results highlight the associations between workplace psychosocial strain and multi-site musculoskeletal pain, setting the stage for future longitudinal explorations. C1 [Sembajwe, Grace] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10035 USA. [Tveito, Torill Helene] Univ Bergen, Dept Hlth Promot & Dev, N-5020 Bergen, Norway. [Hopcia, Karen] Univ Illinois, Coll Nursing, Occupat Hlth Nursing Program, Chicago, IL USA. [Kenwood, Christopher] New England Res Inst, Watertown, MA 02172 USA. [O'Day, Elizabeth Tucker; Hashimoto, Dean] Partners HealthCare Inc, Boston, MA USA. [Stoddard, Anne M.] New England Res Inst, Ctr Stat Anal & Res, Watertown, MA 02172 USA. [Dennerlein, Jack T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Dennerlein, Jack T.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Sembajwe, G (reprint author), CUNY Hunter Coll, Sch Publ Hlth, 2180 3rd Ave,Room 527, New York, NY 10035 USA. EM gsembajw@hunter.cuny.edu OI Dennerlein, Jack/0000-0001-7703-643X FU National Institute for Occupational Safety and Health [U19 OH008861] FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard School of Public Health Center for Work, Health and Wellbeing. NR 72 TC 13 Z9 14 U1 5 U2 32 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2165-0799 J9 WORKPLACE HEALTH SAF JI Workplace Health Saf. PD MAR PY 2013 VL 61 IS 3 BP 117 EP 125 DI 10.3928/21650799-20130226-01 PG 9 WC Nursing SC Nursing GA 173TP UT WOS:000321103000004 PM 23452130 ER PT J AU Wang, C Zhang, N Zhang, YL Zhang, J Yang, H Timothy, TC AF Wang, C. Zhang, N. Zhang, Y. L. Zhang, J. Yang, H. Timothy, T. C. TI Comparison of the neurobiological effects of attribution retraining group therapy with those of selective serotonin reuptake inhibitors SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE Attribution retraining group therapy; Selective serotonin reuptake inhibitors; Neurobiological effects; Serotonin; Cortisol ID MAJOR DEPRESSION; ANXIETY; DISORDER; MODULATION; ACTIVATION; CORTISOL; STATES; MODEL; SCALE; STYLE AB The aim of this study was to compare the effectiveness of attribution retraining group therapy (ARGT) with selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), and obsessive-compulsive disorder (OCD). Subjects were sequentially recruited and randomized into two groups, one receiving ARGT (n = 63) and the other SSRIs (n = 66) for 8 weeks. Fifty-four ARGT outpatients with MDD (n = 19), GAD (n = 19), and OCD (n = 16) and 55 SSRI outpatients with MDD (n = 19), GAD (n = 19), and OCD (n = 17) completed the study. All subjects were assessed using the Hamilton Depression Scale and Hamilton Anxiety Scale before and after treatment. The 10-item Yale-Brown Obsessive Compulsive Scale was employed only for OCD subjects. Plasma levels of serotonin, norepinephrine, cortisol, and adrenocorticotropic hormone were also measured at baseline and 8 weeks after completion of treatment. Symptom scores were significantly redu(c)ed (P < 0.001) in both the ARGT and SSRI groups at the end of treatment. However, MDD, GAD and OCD patients in the ARGT group had significantly lower plasma cortisol concentrations compared to baseline (P < 0.05), whereas MDD and OCD patients receiving SSRIs showed significantly increased plasma levels of serotonin (P < 0.05). These findings suggest that ARGT may modulate plasma cortisol levels and affect the hypothalamus-pituitary-adrenal axis as opposed to SSRIs, which may up-regulate plasma serotonin levels via a different pathway to produce an overall improvement in the clinical condition of the patients. C1 [Wang, C.; Zhang, N.; Zhang, J.; Yang, H.] Nanjing Med Univ, Nanjing Brain Hosp, Dept Med Psychol, Nanjing 210029, Jiangsu, Peoples R China. [Wang, C.; Zhang, Y. L.; Zhang, J.] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha 410011, Hunan, Peoples R China. [Timothy, T. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zhang, N (reprint author), Nanjing Med Univ, Nanjing Brain Hosp, Nanjing 210029, Jiangsu, Peoples R China. EM zn6360@126.com; zhangyl69@vip.sina.com FU National Science and Technology Support Projects, China [2009BA177B07]; National Natural Science Foundation for Youth of China [81201064]; Nanjing Medical Science and Technique Development Youth Foundation, China [QYK09184] FX Research supported by the National Science and Technology Support Projects, China (#2009BA177B07), the National Natural Science Foundation for Youth of China (#81201064), and the Nanjing Medical Science and Technique Development Youth Foundation, China (#QYK09184). NR 36 TC 1 Z9 3 U1 1 U2 8 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, 00, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD MAR PY 2013 VL 46 IS 3 BP 318 EP 326 DI 10.1590/1414-431X20122658 PG 9 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 158WG UT WOS:000320004000016 PM 23558857 ER PT J AU Woods, SS Schwartz, E Tuepker, A Press, NA Nazi, KM Turvey, CL Nichol, P AF Woods, Susan S. Schwartz, Erin Tuepker, Anais Press, Nancy A. Nazi, Kim M. Turvey, Carolyn L. Nichol, Paul TI Patient Experiences With Full Electronic Access to Health Records and Clinical Notes Through the My HealtheVet Personal Health Record Pilot: Qualitative Study SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE personal health records; eHealth; patient access to records; veterans; patient participation ID MEDICAL-RECORD; INVITING PATIENTS; GENERAL-PRACTICE; DOCTORS NOTES; CARE RECORD; COMMUNICATION; EXPECTATIONS; INFORMATION; ATTITUDES; TRIAL AB Background: Full sharing of the electronic health record with patients has been identified as an important opportunity to engage patients in their health and health care. The My HealtheVet Pilot, the initial personal health record of the US Department of Veterans Affairs, allowed patients and their delegates to view and download content in their electronic health record, including clinical notes, laboratory tests, and imaging reports. Objective: A qualitative study with purposeful sampling sought to examine patients' views and experiences with reading their health records, including their clinical notes, online. Methods: Five focus group sessions were conducted with patients and family members who enrolled in the My HealtheVet Pilot at the Portland Veterans Administration Medical Center, Oregon. A total of 30 patients enrolled in the My HealtheVet Pilot, and 6 family members who had accessed and viewed their electronic health records participated in the sessions. Results: Four themes characterized patient experiences with reading the full complement of their health information. Patients felt that seeing their records positively affected communication with providers and the health system, enhanced knowledge of their health and improved self-care, and allowed for greater participation in the quality of their care such as follow-up of abnormal test results or decision-making on when to seek care. While some patients felt that seeing previously undisclosed information, derogatory language, or inconsistencies in their notes caused challenges, they overwhelmingly felt that having more, rather than less, of their health record information provided benefits. Conclusions: Patients and their delegates had predominantly positive experiences with health record transparency and the open sharing of notes and test results. Viewing their records appears to empower patients and enhance their contributions to care, calling into question common provider concerns about the effect of full record access on patient well-being. While shared records may or may not impact overall clinic workload, it is likely to change providers' work, necessitating new types of skills to communicate and partner with patients. C1 [Woods, Susan S.; Schwartz, Erin; Tuepker, Anais] Portland VA Med Ctr, Portland, OR 97239 USA. [Woods, Susan S.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Press, Nancy A.] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. [Press, Nancy A.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Nazi, Kim M.] Vet Hlth Adm, Vet & Consumers Hlth Informat Off, Off Informat & Analyt, Washington, DC USA. [Turvey, Carolyn L.] Iowa City VA Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Nichol, Paul] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Woods, SS (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd P3HSRD, Portland, OR 97239 USA. EM susan.woods@va.gov NR 26 TC 45 Z9 45 U1 6 U2 23 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD MAR PY 2013 VL 15 IS 3 BP 182 EP 191 DI 10.2196/jmir.2356 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 151EA UT WOS:000319442300015 PM 23535584 ER PT J AU Tannock, LR AF Tannock, Lisa R. TI U-500: A CONVENIENT INSULIN FOR A CONVENIENCE FOOD NATION SO ENDOCRINE PRACTICE LA English DT Editorial Material ID DIABETES-MELLITUS C1 [Tannock, Lisa R.] Univ Kentucky, US Dept Vet Affairs, Lexington, KY 40536 USA. [Tannock, Lisa R.] Univ Kentucky, Div Endocrinol & Mol Med, Lexington, KY 40536 USA. RP Tannock, LR (reprint author), Univ Kentucky, Room 553,Wethington Bldg,900 S Limestone St, Lexington, KY 40536 USA. EM Lisa.Tannock@uky.edu NR 9 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAR-APR PY 2013 VL 19 IS 2 BP 194 EP 195 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 154JX UT WOS:000319672400005 PM 23598533 ER PT J AU Fleseriu, M Molitch, ME Gross, C Schteingart, DE Vaughan, B Biller, BMK AF Fleseriu, Maria Molitch, Mark E. Gross, Coleman Schteingart, David E. Vaughan, Brooks, III Biller, Beverly M. K. TI A NEW THERAPEUTIC APPROACH IN THE MEDICAL TREATMENT OF CUSHING'S SYNDROME: GLUCOCORTICOID RECEPTOR BLOCKADE WITH MIFEPRISTONE SO ENDOCRINE PRACTICE LA English DT Review ID ECTOPIC ADRENOCORTICOTROPIN SECRETION; LONG-TERM TREATMENT; TRANSSPHENOIDAL SURGERY; CONSENSUS STATEMENT; CARDIOVASCULAR RISK; ANTAGONIST RU-486; MITOTANE THERAPY; CORTISOL-LEVELS; SINGLE-CENTER; DISEASE AB Objective: Cushing's syndrome (CS) is a serious endocrine disorder caused by prolonged exposure to high cortisol levels. Initial treatment of this condition is dependent upon the cause, but is generally surgical. For patients whose hypercortisolism is not cured by surgery, medical therapy is often required. Drugs that have typically been used for CS medical therapy act by decreasing cortisol levels. Mifepristone is a glucocorticoid receptor antagonist now available for use in patients with CS. Unlike other agents, mifepristone does not decrease cortisol levels, but directly antagonizes its effects. Our objective is to review the pharmacology and clinical use of this novel agent and to discuss detailed guidance on the management of CS patients treated with mifepristone. Methods: We review the literature regarding mifepristone use in CS and recently published clinical trial data. Detailed information related to clinical assessment of mifepristone use, potential drug interactions, drug initiation and dose titration, and monitoring of drug tolerability are provided. Results: Clinical trial data have shown that mifepristone improves glycemic control and blood pressure, causes weight loss and a decrease in waist circumference, lessens depression, and improves overall wellbeing. However, adverse effects include adrenal insufficiency, hypokalemia, and endometrial thickening with vaginal bleeding. These findings are supported by the earlier literature case reports. Conclusion: This article provides a review of the pharmacology and clinical use of mifepristone in Cushing's syndrome, as well as detailed guidance on the management of patients treated with this novel agent. C1 [Fleseriu, Maria] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Molitch, Mark E.] Northwestern Univ, Feinberg Med Sch, Chicago, IL 60611 USA. [Gross, Coleman] Corcept Therapeut, Menlo Pk, CA USA. [Schteingart, David E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Vaughan, Brooks, III] Univ Alabama Birmingham, Birmingham, AL USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fleseriu, M (reprint author), Oregon Hlth & Sci Univ, Dept Med, Northwest Pituitary Ctr, 3181 SW Sam,Jackson Pk Rd BTE 472, Portland, OR 97239 USA. EM fleseriu@ohsu.edu FU Corcept Therapeutics, Inc.; Novartis FX B. M. K. B and M. E. M. consulted for Corcept Therapeutics, Inc. B. M. K. B., M. E. M., M. F., T. B. V., and D. E. S. served as investigators on research grants to their institutions from Corcept Therapeutics, Inc. B. M. K. B. and M. F. are consultants to, and serve as investigators on, research grants to their institutions from Novartis. B. M. K. B., M. F., and T. B. V. serve as consultants to Ipsen. C. G. is an employee of Corcept Therapeutics. All drafts of the manuscript were written and reviewed by all the authors. NR 75 TC 18 Z9 18 U1 0 U2 6 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAR-APR PY 2013 VL 19 IS 2 BP 313 EP 326 DI 10.4158/EP12149.RA PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 154JX UT WOS:000319672400023 PM 23337135 ER PT J AU Mechanick, JI Youdim, A Jones, DB Garvey, WT Hurley, DL McMahon, MM Heinberg, LJ Kushner, R Adams, TD Shikora, S Dixon, JB Brethauer, S AF Mechanick, Jeffrey I. Youdim, Adrienne Jones, Daniel B. Garvey, W. Timothy Hurley, Daniel L. McMahon, M. Molly Heinberg, Leslie J. Kushner, Robert Adams, Ted D. Shikora, Scott Dixon, John B. Brethauer, Stacy TI CLINICAL PRACTICE GUIDELINES FOR THE PERIOPERATIVE NUTRITIONAL, METABOLIC, AND NONSURGICAL SUPPORT OF THE BARIATRIC SURGERY PATIENT-2013 UPDATE: COSPONSORED BY AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, THE OBESITY SOCIETY, AND AMERICAN SOCIETY FOR METABOLIC & BARIATRIC SURGERY SO ENDOCRINE PRACTICE LA English DT Article ID Y-GASTRIC-BYPASS; LAPAROSCOPIC-SLEEVE-GASTRECTOMY; TYPE-2 DIABETES-MELLITUS; WEIGHT-LOSS SURGERY; BODY-MASS INDEX; PROSPECTIVE-RANDOMIZED-TRIAL; OF-THE-LITERATURE; OUTCOMES LONGITUDINAL DATABASE; HELICOBACTER-PYLORI INFECTION; CARDIOVASCULAR RISK-FACTORS AB The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE- TOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues. C1 [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, New York, NY 10128 USA. [Youdim, Adrienne] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Jones, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Birmingham VA Med Ctr, AACE, Birmingham, AL USA. [Hurley, Daniel L.; McMahon, M. Molly] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, AACE, Rochester, MN USA. [Heinberg, Leslie J.] Cleveland Clin, Lerner Coll Med, TOS, Cleveland, OH 44106 USA. [Kushner, Robert] Northwestern Univ, Feinberg Sch Med, TOS, Chicago, IL 60611 USA. [Adams, Ted D.] Univ Utah, Sch Med, Intermt Healthcare & Cardiovasc Genet Div, Hlth & Fitness Inst,TOS, Salt Lake City, UT USA. [Shikora, Scott] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Metab Hlth & Bariatr Surg,ASMBS, Boston, MA 02115 USA. [Dixon, John B.] Monash Univ, Baker IDI Heart & Diabet Inst, ASMBS, Melbourne, Vic 3004, Australia. [Brethauer, Stacy] Cleveland Clin, Bariatr & Metab Inst, ASMBS, Cleveland, OH 44106 USA. RP Mechanick, JI (reprint author), Icahn Sch Med Mt Sinai, 1192 Pk Ave, New York, NY 10128 USA. EM jeffreymechanick@gmail.com NR 387 TC 37 Z9 38 U1 1 U2 10 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAR-APR PY 2013 VL 19 IS 2 BP 338 EP 372 PG 35 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 154JX UT WOS:000319672400025 ER PT J AU Mack, J Okai, D Brown, RG Askey-Jones, S Chaudhuri, KR Martin, A Samuel, M David, AS AF Mack, Joel Okai, David Brown, Richard G. Askey-Jones, Sally Chaudhuri, K. Ray Martin, Anne Samuel, Michael David, Anthony S. TI The Role of Self-Awareness and Cognitive Dysfunction in Parkinson's Disease With and Without Impulse-Control Disorder SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID DOPAMINE DYSREGULATION; PSYCHOTIC SYMPTOMS; HALLUCINATIONS; STIMULATION; PREVALENCE; DYSKINESIAS; INVENTORY; DIAGNOSIS; RATINGS; SCALE AB The aim of this study was to investigate the clinical, neuropsychological, and self-awareness correlates of impulse-control disorder (ICD) in a group of 17 Parkinson's disease (PD) subjects with an active ICD and a comparison group of 17 PD subjects without ICD. Self-awareness was assessed with the Beck Cognitive Insight Scale and patient-caregiver discrepancy scores from ratings on the Dysexecutive Questionnaire and the Everyday Memory Questionnaire-Revised. Self-awareness was comparable or increased in those with ICD, versus those without, and measures of neuropsychological functioning did not differ between the two groups. Those with ICD had more motor complications of PD therapy and were more likely to be on an antidepressant than those without ICD, whereas dopaminergic medication profiles were comparable between the two groups. In this group, PD patients with current ICDs were aware of their impulsivity. Although executive dysfunction may contribute to ICD behavior, it is not a necessary component. The awareness of the inability to resist these motivated behaviors may be a source of increased depression. C1 Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. Portland VA Med Ctr, Northwest Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. Kings Coll London, Inst Psychiat, Sect Cognit Neuropsychiat, London WC2R 2LS, England. Imperial Healthcare NHS Trust, London, England. West London Mental Hlth Trust, London, England. Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England. Kings Coll London, Dept Mental Hlth & Specialist Care, Florence Nightingale Sch Nursing & Midwifery, London, England. Kings Hlth Partners, Kings Coll Hosp, Dept Neurol, Natl Parkinson Fdn Ctr Excellence, London, England. East Kent Hosp Univ NHS Fdn Trust, William Harvey Hosp, Ashford, Kent, England. RP Mack, J (reprint author), Portland VA Med Ctr, Portland, OR USA. EM mack@ohsu.edu RI Brown, Richard/A-9599-2010; David, Anthony/C-1315-2011; OI Brown, Richard/0000-0001-9021-0172; David, Anthony/0000-0003-0967-774X; Okai, David/0000-0002-0298-2031; Ray Chaudhuri, K/0000-0003-2815-0505 FU Parkinson's UK; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London; Maudsley NHS Foundation Trust and King's College, London; Medtronic, Inc.; St. Judes, Inc.; Ipsen Pharmaceuticals; Solvay Pharmaceuticals; UCB Pharma, Britannia; GSK; Abbott; Teva; Medtronic; Boehringer Ingelheim; UCB Pharma; Britannia FX The authors acknowledge support from: Parkinson's UK; Authors RGB and ASD acknowledge support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College, London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.; Relevant conflicts of interest/financial disclosures: RGB has received honoraria for speaking at conferences and educational events from UCB Pharma, GSK, Lundbeck, and is an Advisory Board member for UCB Pharma. MS has received lecture fees from Medtronic, Inc., St. Judes, Inc., unrestricted educational grants from Ipsen and Solvay Pharmaceuticals, and sponsorship for educational meetings from Boehringer Ingelheim. KRC serves as the European Editor of Basal Ganglia, as an editorial board member of Parkinsonism and Related Disorders, and The Journal of Parkinson's Disease, and, as the Liaison and PR Committee Chairman of the Movement Disorders Society, has received honoraria for academic lectures at sponsored symposiums from UCB Pharma, Britannia, GSK, Abbott, Teva, Medtronic, and Boehringer Ingelheim, and has received educational grants for research from UCB Pharma, Abbott, Boehringer Ingelheim, and Britannia. NR 51 TC 5 Z9 5 U1 1 U2 14 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2013 VL 25 IS 2 BP 141 EP 149 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156FX UT WOS:000319808300048 PM 23686032 ER PT J AU Daniels, LB Grady, D Mosca, L Collins, P Mitlak, BH Amewou-Atisso, MG Wenger, NK Barrett-Connor, E AF Daniels, Lori B. Grady, Deborah Mosca, Lori Collins, Peter Mitlak, Bruce H. Amewou-Atisso, Messan G. Wenger, Nanette K. Barrett-Connor, Elizabeth CA Raloxifene Use Heart RUTH Trial In TI Is Diabetes Mellitus a Heart Disease Equivalent in Women? Results From an International Study of Postmenopausal Women in the Raloxifene Use for the Heart (RUTH) Trial SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE diabetes mellitus; heart diseases; randomized trial; risk factors; women ID PRIOR MYOCARDIAL-INFARCTION; FACTOR INTERVENTION TRIAL; CARDIOVASCULAR-DISEASE; FOLLOW-UP; DOPPLER ECHOCARDIOGRAPHY; NONDIABETIC INDIVIDUALS; RISK EQUIVALENT; MORTALITY; POPULATION; IMPACT AB Background-Several studies have concluded that diabetes mellitus and heart disease carry similar risk for future cardiovascular disease (CVD). Most of these studies were too small to quantify independent risks specific to women. The purpose of this study was to determine whether diabetes mellitus is a coronary heart disease (CHD) risk equivalent for prediction of future CHD and CVD events in women. Methods and Results-The Raloxifene Use for the Heart (RUTH) trial was an international, multicenter, double-blind, randomized, placebo-controlled trial of raloxifene and CVD outcomes in 10 101 postmenopausal women selected for high CHD risk. Of these, 3672 had a history of diabetes mellitus without known CHD, and 3265 had a history of CHD without known diabetes mellitus. Cox proportional hazard models were used to compare cardiovascular outcomes in these 2 groups. Mean age at baseline was 67.5 years; median follow-up was 5.6 years. There were 725 deaths, including 450 cardiovascular deaths. In age-adjusted analyses, diabetic women had an increased risk of all-cause mortality compared with women with CHD. Although the overall risk of CHD and CVD was lower in diabetic women compared with women with CHD, the risk of fatal CHD, fatal CVD, and all-cause mortality was similar (hazard ratio [95% confidence interval]: 0.85 [0.65-1.12], 0.99 [0.78-1.25], and 1.18 [0.98-1.42], respectively, after adjusting for age, lifestyle factors, CHD risk factors, statin use, and treatment assignment). Conclusions-In the RUTH trial, diabetes mellitus was a CHD risk equivalent in women for fatal, but not nonfatal, CHD and CVD. C1 [Daniels, Lori B.] UC San Diego Hlth Syst, Dept Med, Div Cardiol, La Jolla, CA USA. [Barrett-Connor, Elizabeth] UC San Diego Hlth Syst, Dept Family & Prevent Med, Div Epidemiol, La Jolla, CA USA. [Grady, Deborah] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. [Mosca, Lori] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Collins, Peter] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Dept Cardiac Med, London, England. [Collins, Peter] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Mitlak, Bruce H.; Amewou-Atisso, Messan G.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Wenger, Nanette K.] Emory Univ, Sch Med, Atlanta, GA USA. RP Daniels, LB (reprint author), Univ Calif San Diego, Div Cardiol, Mail Code 7411,9444 Med Ctr Dr, La Jolla, CA 92037 USA. EM lbdaniels@ucsd.edu RI Suryapranata, H./H-8095-2014; Gurevich, Victor/H-2935-2013; OI Gurevich, Victor/0000-0002-6815-444X; Maggioni, Aldo Pietro/0000-0003-2764-6779 FU Eli Lilly and Company, Indianapolis, IN FX This study was sponsored by Eli Lilly and Company, Indianapolis, IN. NR 42 TC 9 Z9 9 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2013 VL 6 IS 2 BP 164 EP + DI 10.1161/CIRCOUTCOMES.112.966986 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150LO UT WOS:000319392100007 PM 23481531 ER PT J AU Merchant, RM Asch, DA Hershey, JC Griffis, HM Hill, S Saynisch, O Leung, AC Asch, JM Lozada, K Nadkarni, LD Kilaru, A Branas, CC Stone, EM Starr, L Shofer, F Nichol, G Becker, LB AF Merchant, Raina M. Asch, David A. Hershey, John C. Griffis, Heather M. Hill, Shawndra Saynisch, Olivia Leung, Alison C. Asch, Jeremy M. Lozada, Kirk Nadkarni, Lindsay D. Kilaru, Austin Branas, Charles C. Stone, Eric M. Starr, Larry Shofer, Frances Nichol, Graham Becker, Lance B. TI A Crowdsourcing Innovation Challenge to Locate and Map Automated External Defibrillators SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cardiopulmonary resuscitation; crowdsourcing; defibrillator; heart arrest ID HOSPITAL CARDIAC-ARREST; PUBLIC-ACCESS DEFIBRILLATION; AMERICAN-HEART-ASSOCIATION; UNITED-STATES; SURVIVAL; OUTCOMES; CARE C1 [Merchant, Raina M.; Griffis, Heather M.; Saynisch, Olivia; Leung, Alison C.; Asch, Jeremy M.; Lozada, Kirk; Nadkarni, Lindsay D.; Stone, Eric M.; Shofer, Frances; Becker, Lance B.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Merchant, Raina M.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.; Hershey, John C.; Hill, Shawndra] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Branas, Charles C.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Nichol, Graham] Univ Washington, Dept Med, Univ Washington Harborview Ctr Prehosp Emergency, Seattle, WA USA. RP Merchant, RM (reprint author), Univ Penn, Perelman Sch Med, 423 Guardian St,1022 Blockley, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation Health and Society Scholars Program at the University of Pennsylvania, National Institutes of Health (NIH) [10714038]; Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; Philips Medical, Seattle, WA; Medtronic Foundation Heart Rescue Project; Penn University Research Fund; McCabe Fund FX This study was supported by the Robert Wood Johnson Foundation Health and Society Scholars Program at the University of Pennsylvania, National Institutes of Health (NIH), K23 Grant 10714038, and pilot funding from Physio-Control, Seattle, WA; Zoll Medical, Boston, MA; Cardiac Science, Bothell, WA; and Philips Medical, Seattle, WA, as well as The Medtronic Foundation Heart Rescue Project; The Penn University Research Fund; and the McCabe Fund. No funders played a 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 25 TC 18 Z9 18 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2013 VL 6 IS 2 BP 229 EP + DI 10.1161/CIRCOUTCOMES.113.000140 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 150LO UT WOS:000319392100016 PM 23481522 ER PT J AU Styskal, J Nwagwu, FA Watkins, YN Liang, H Richardson, A Musi, N Salmon, AB AF Styskal, JennaLynn Nwagwu, Florence A. Watkins, Yvonne N. Liang, Hanyu Richardson, Arlan Musi, Nicolas Salmon, Adam B. TI Methionine sulfoxide reductase A affects insulin resistance by protecting insulin receptor function SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Oxidative stress; Methionine sulfoxide; Diabetes; Obesity; Glucose homeostasis; Protein oxidation ID HUMAN SKELETAL-MUSCLE; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; GLUT4 TRANSLOCATION; 3T3-L1 ADIPOCYTES; ADIPOSE-TISSUE; OBESITY; PHOSPHORYLATION AB Oxidative stress plays a significant role in the development of insulin resistance; however, the cellular targets of oxidation that cause insulin resistance have yet to be fully elucidated. Methionine sulfoxide reductases reduce oxidized methionine residues, thereby repairing and protecting proteins from oxidation. Recently, several genome-wide analyses have found human obesity to be strongly correlated with polymorphisms near the methionine sulfoxide reductase A (MsrA) locus. In this study, we tested whether modulation of MsrA expression significantly alters the development of obesity and/or insulin resistance in mice. We show that mice lacking MsrA (MsrA(-/-)) are prone to the development of high-fat-diet-induced insulin resistance and a reduced physiological insulin response compared to high-fat-fed wild-type mice. We also show that oxidative stress in C2C12 cell cultures reduces both insulin-stimulated phosphorylation and autophosphorylation of the insulin receptor. Tissues from high-fat-fed mice show similar reduction in insulin receptor function and increase in insulin receptor oxidation, which are further exacerbated by the lack of MsrA. Together, these data demonstrate for the first time that MsrA and protein oxidation play a role in the regulation of glucose homeostasis. In addition, these data support a novel hypothesis that obesity-induced insulin resistance is caused in part by reduced function of insulin signaling proteins arising from protein oxidation. Published by Elsevier Inc. C1 [Styskal, JennaLynn; Nwagwu, Florence A.; Watkins, Yvonne N.; Richardson, Arlan; Musi, Nicolas; Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Styskal, JennaLynn; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Nwagwu, Florence A.; Watkins, Yvonne N.; Liang, Hanyu; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Liang, Hanyu; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Richardson, Arlan; Musi, Nicolas; Salmon, Adam B.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Salmon, AB (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM salmona@uthscsa.edu FU National Institutes of Health (NIH) [T32 AG021890-05]; NIH MERIT [R37AG026557]; Mitochondrial Function and Oxidative Damage Core Facility of the San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging FX The authors thank Rodney Levine, Geumsoo Kim, and Hang Zhao from the NIH/NHLBI Laboratory of Biochemistry for sharing MsrA-/- mice to generate our breeding colonies. This study was supported by National Institutes of Health (NIH) Training Grant T32 AG021890-05, NIH MERIT Grant R37AG026557, and the Mitochondrial Function and Oxidative Damage Core Facility of the San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging. NR 49 TC 17 Z9 17 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR PY 2013 VL 56 BP 123 EP 132 DI 10.1016/j.freeradbiomed.2012.10.544 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 154BY UT WOS:000319647700012 PM 23089224 ER PT J AU Shailam, R Jaramillo, D Kan, JH AF Shailam, Randheer Jaramillo, Diego Kan, J. Herman TI Growth arrest and leg-length discrepancy SO PEDIATRIC RADIOLOGY LA English DT Article DE Children; Leg-length discrepancy; Perthes disease; Physeal ID PHYSEAL ARREST; BLOUNT-DISEASE; MR; CHILDREN; KNEE; MANAGEMENT; ARTHRITIS; DEFORMITY AB Identification of congenital and acquired etiologies causing alignment disorders and leg-length discrepancies (LLD) in children is important for management. Minor differences in the lengths of the lower extremities are considered a normal variation and usually have no clinical significance. However, LLD of greater than 1 cm can cause altered biomechanics, resulting in scoliosis, back and lower extremity joint pain, pelvic tilt, abnormal gait and premature degenerative joint disease. The purpose of this pictorial essay is to review the imaging spectrum of growth arrest and resultant alignment and leg-length discrepancies in children. C1 [Shailam, Randheer] Massachusetts Gen Hosp, Pediat Radiol Div, Dept Radiol, Boston, MA 02114 USA. [Jaramillo, Diego] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Kan, J. Herman] Texas Childrens Hosp, Dept Pediat Radiol, Houston, TX 77030 USA. RP Shailam, R (reprint author), Massachusetts Gen Hosp, Pediat Radiol Div, Dept Radiol, 55 Fruit St,Ellison 2, Boston, MA 02114 USA. EM rshailam@partners.org NR 23 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD MAR PY 2013 VL 43 SU 1 BP S155 EP S165 DI 10.1007/s00247-012-2598-5 PG 11 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 143QH UT WOS:000318881800018 PM 23478931 ER PT J AU Utrera-Lagunas, M Orea-Tejeda, A Castillo-Martinez, L Balderas-Munoz, K Keirns-Davis, C Espinoza-Rosas, S Sanchez-Ortiz, NA Olvera-Mayorga, G AF Utrera-Lagunas, Marcelo Orea-Tejeda, Arturo Castillo-Martinez, Lilia Balderas-Munoz, Karla Keirns-Davis, Candace Espinoza-Rosas, Sarahi Alonso Sanchez-Ortiz, Nestor Olvera-Mayorga, Gabriela TI Abnormal myocardial perfusion and risk of heart failure in patients with type 2 diabetes mellitus SO EXPERIMENTAL & CLINICAL CARDIOLOGY LA English DT Article DE Diabetes mellitus; Heart failure; Myocardial perfusion ID COMPLICATIONS; DYSFUNCTION; TRIAL AB BACKGROUND: Diabetes is a major risk factor for heart failure (HF), although the pathophysiological processes have not been clarified. OBJECTIVE: To determine the prevalence of HF and of abnormal myocardial perfusion in diabetic patients evaluated using technetium (99m) sestamibi single-photon emission computed tomography. METHODS: An observational cross-sectional study was conducted that included patients with type 2 diabetes mellitus who underwent echocardiography to diagnose HF and a pharmacological stress test with intravenous dipyridamole to examine cardiac scintigraphic perfusion abnormalities. Clinical and biochemical data were also collected. RESULTS: Of the 160 diabetic patients included, 92 (57.6%) were in HF and 68 (42.5%) were not. When patients were stratified according to the presence of abnormal myocardial perfusion, those with abnormal perfusion had a higher prevalence of HF (93%) than those with normal perfusion (44.4%) (P<0.0001). Patients with HF weighed more (P=0.03), used insulin less frequently (P=0.01), had lower total cholesterol (P=0.05) and high-density lipoprotein cholesterol concentrations (P=0.002), and a greater number of their myocardial segments showed abnormal perfusion (P=0.001). More HF patients had a history of myocardial infarction (P<0.001) compared with those without HF. In a logistic regression analysis, the number of segments exhibiting abnormal myocardial perfusion was an independent risk factor for HF. CONCLUSIONS: The prevalence of HF in diabetic patients was high and HF predominantly occured in association with myocardial ischemia. C1 [Utrera-Lagunas, Marcelo; Orea-Tejeda, Arturo; Castillo-Martinez, Lilia; Balderas-Munoz, Karla; Espinoza-Rosas, Sarahi; Alonso Sanchez-Ortiz, Nestor; Olvera-Mayorga, Gabriela] HF Clin, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Boston, MA USA. [Keirns-Davis, Candace] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Castillo-Martinez, L (reprint author), HF Clin INCMNSZ, Providencia 1218-A Int 402, Mexico City 03100, DF, Mexico. EM cam7125@gmail.com RI Castillo-Martinez, Lilia/H-3750-2013 NR 14 TC 0 Z9 0 U1 1 U2 2 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 1205-6626 J9 EXP CLIN CARDIOL JI Exp. Clin. Cardiol. PD SPR PY 2013 VL 18 IS 1 BP E44 EP E46 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 148CB UT WOS:000319219000011 PM 24294048 ER PT J AU Fisher-Owens, SA Isong, IA Soobader, MJ Gansky, SA Weintraub, JA Platt, LJ Newacheck, PW AF Fisher-Owens, Susan A. Isong, Inyang A. Soobader, Mah-J Gansky, Stuart A. Weintraub, Jane A. Platt, Larry J. Newacheck, Paul W. TI An examination of racial/ethnic disparities in children's oral health in the United States SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE children; oral health; race; ethnic disparities ID SELF-RATED HEALTH; SOCIOECONOMIC-STATUS; NATIONAL-SURVEY; WHITES; CARE; BLACKS; RACE/ETHNICITY; POPULATIONS; PERCEPTIONS; LANGUAGE AB Objective: To assess the extent factors other than race/ethnicity explain apparent racial/ethnic disparities in children's oral health and oral health care. Methods: Data were from the 2007 National Survey of Children's Health, for children 2-17 years (n=82,020). Outcomes included parental reports of child's oral health status, receiving preventive dental care, and delayed dental care/unmet need. Model-based survey-data-analysis examined racial/ethnic disparities, controlling for child, family, and community/state (contextual) factors. Results: Unadjusted results show large racial/ethnic oral health disparities. Compared with non-Hispanic White people, Hispanic and non-Hispanic-Black people were markedly more likely to be reported in only fair/poor oral health [odds ratios (ORs) (95% confidence intervals) 4.3 (4.0-4.6), 2.2 (2.0-2.4), respectively], lack preventive care [ORs 1.9 (1.8-2.0), 1.4 (1.3-1.5)], and experience delayed care/unmet need [ORs 1.5 (1.3-1.7), 1.4 (1.3-1.5)]. Adjusting for child, family, and community/state factors reduced racial/ethnic disparities. Adjusted ORs (AORs) for Hispanics and non-Hispanic Blacks attenuated for fair/poor oral health, to 1.6 (1.5-1.8) and 1.2 (1.1-1.4), respectively. Adjustment eliminated disparities for lacking preventive care [AORs 1.0 (0.9-1.1), 1.1 (1.1-1.2)] and in Hispanics for delayed care/unmet need (AOR 1.0). Among non-Hispanic Blacks, adjustment reversed the disparity for delayed care/unmet need [AOR 0.6 (0.6-0.7)]. Conclusions: Racial/ethnic disparities in children's oral health status and access were attributable largely to socioeconomic and health insurance factors. Efforts to decrease disparities may be more efficacious if targeted at social, economic, and other factors associated with minority racial/ethnic status and may have positive effects on all who share similar social, economic, and cultural characteristics. C1 [Fisher-Owens, Susan A.] Univ Calif San Francisco, Dept Pediat, Sch Med, San Francisco, CA 94110 USA. [Isong, Inyang A.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp,Ctr Child & Adolescent Hlt, Boston, MA 02115 USA. [Soobader, Mah-J] Statworks, Boston, MA USA. [Gansky, Stuart A.] UCSF Sch Dent, Dept Prevent & Restorat Dent Sci, San Francisco, CA USA. [Weintraub, Jane A.] Univ N Carolina, Sch Dent, Deans Off, Chapel Hill, NC USA. [Platt, Larry J.; Newacheck, Paul W.] UCSF Sch Med, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [Newacheck, Paul W.] UCSF Sch Med, Dept Pediat, San Francisco, CA USA. RP Fisher-Owens, SA (reprint author), Univ Calif San Francisco, Dept Pediat, Sch Med, 1001 Potrero Ave,MS 6E37, San Francisco, CA 94110 USA. EM fisherowens@peds.ucsf.edu OI Fisher-Owens, Susan/0000-0002-2482-1220 FU [US DHHS NIH R21 DEO18523] FX Grant number US DHHS NIH R21 DEO18523, Lena Libatique for her outstanding support, and anonymous reviewers for their helpful comments. NR 44 TC 12 Z9 12 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SPR PY 2013 VL 73 IS 2 BP 166 EP 174 DI 10.1111/j.1752-7325.2012.00367.x PG 9 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 150SD UT WOS:000319410400012 PM 22970900 ER PT J AU Kaatz, A Vogelman, PN Carnes, M AF Kaatz, Anna Vogelman, Paul N. Carnes, Molly TI Are Men More Likely than Women To Commit Scientific Misconduct? Maybe, Maybe Not SO MBIO LA English DT Editorial Material ID GENDER; STEREOTYPES; SUCCESS AB In their study published in January 2013 in mBio, Fang et al. reviewed records from the Office of Research Integrity (ORI) and found more cases of scientific misconduct committed by men than women, particularly by faculty (F. C. Fang, J. W. Bennett, and A. Casadevall, mBio 4:1-3, 2013). Powerful social norms shape the way men and women behave, and implicit gender schemas can lead to different evaluation standards for men and women for tasks stereotypically linked to one gender. It is possible that norms for acceptable male and female behavior could lead to a lower threshold for men than women to engage in the risky behavior of scientific misconduct. It is also possible that women and men commit scientific fraud at the same rate but that, because crime is a male-gendered domain, evaluators require more proof of the criminal "competence" of women for an investigation to rise to the level of an ORI case or that female gender norms for likeability and a lower apology threshold more often prevent escalation of women's fraud beyond a local level. Male scientists also have more opportunity to commit fraud than female scientists because they receive more NIH research funding-a finding that may also be influenced by gender schemas. We cannot conclude from the ORI data that men are more likely than women to risk the consequences of committing scientific misconduct simply because risk taking aligns with male gender stereotypes. Neither can we conclude that because men are more likely than women to commit fraud in other contexts, men are also more likely than women to commit scientific fraud. We can conclude, however, that scientific misconduct, regardless of who commits it, diminishes all who contribute to the scientific enterprise. C1 [Kaatz, Anna; Carnes, Molly] Univ Wisconsin Madison, Ctr Womens Hlth Res, Madison, WI 53706 USA. [Carnes, Molly] Univ Wisconsin Madison, Dept Med, Madison, WI USA. [Carnes, Molly] Univ Wisconsin Madison, Dept Ind & Syst Engn, Madison, WI USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Carnes, M (reprint author), Univ Wisconsin Madison, Ctr Womens Hlth Res, Madison, WI 53706 USA. EM mlcarnes@wisc.edu NR 23 TC 2 Z9 2 U1 7 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2013 VL 4 IS 2 AR e00156-13 DI 10.1128/mBio.00156-13 PG 2 WC Microbiology SC Microbiology GA 137JI UT WOS:000318431500025 ER PT J AU Robinson, CM Zhou, XH Rajaiya, J Yousuf, MA Singh, G DeSerres, JJ Walsh, MP Wong, S Seto, D Dyer, DW Chodosh, J Jones, MS AF Robinson, Christopher M. Zhou, Xiaohong Rajaiya, Jaya Yousuf, Mohammad A. Singh, Gurdeep DeSerres, Joshua J. Walsh, Michael P. Wong, Sallene Seto, Donald Dyer, David W. Chodosh, James Jones, Morris S. TI Predicting the Next Eye Pathogen: Analysis of a Novel Adenovirus SO MBIO LA English DT Article ID ACUTE RESPIRATORY-DISEASE; GENOME SEQUENCE; EPIDEMIC KERATOCONJUNCTIVITIS; BIOINFORMATICS ANALYSIS; COMPUTATIONAL ANALYSIS; DNA-SEQUENCE; PENTON BASE; BINDING; CELLS; GENE AB For DNA viruses, genetic recombination, addition, and deletion represent important evolutionary mechanisms. Since these genetic alterations can lead to new, possibly severe pathogens, we applied a systems biology approach to study the pathogenicity of a novel human adenovirus with a naturally occurring deletion of the canonical penton base Arg-Gly-Asp (RGD) loop, thought to be critical to cellular entry by adenoviruses. Bioinformatic analysis revealed a new highly recombinant species D human adenovirus (HAdV-D60). A synthesis of in silico and laboratory approaches revealed a potential ocular tropism for the new virus. In vivo, inflammation induced by the virus was dramatically greater than that by adenovirus type 37, a major eye pathogen, possibly due to a novel alternate ligand, Tyr-Gly-Asp (YGD), on the penton base protein. The combination of bioinformatics and laboratory simulation may have important applications in the prediction of tissue tropism for newly discovered and emerging viruses. IMPORTANCE The ongoing dance between a virus and its host distinctly shapes how the virus evolves. While human adenoviruses typically cause mild infections, recent reports have described newly characterized adenoviruses that cause severe, sometimes fatal human infections. Here, we report a systems biology approach to show how evolution has affected the disease potential of a recently identified novel human adenovirus. A comprehensive understanding of viral evolution and pathogenicity is essential to our capacity to foretell the potential impact on human disease for new and emerging viruses. C1 [Robinson, Christopher M.; Zhou, Xiaohong; Rajaiya, Jaya; Yousuf, Mohammad A.; Singh, Gurdeep; Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Howe Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [DeSerres, Joshua J.; Wong, Sallene] Prov Lab Publ Hlth, Calgary, AB, Canada. [Walsh, Michael P.; Seto, Donald; Jones, Morris S.] George Mason Univ, Sch Syst Biol, Manassas, VA USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Howe Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. EM james_chodosh@meei.harvard.edu; mjones30@gmu.edu FU NIH [EY013124, EY021558, EY014104]; Research to Prevent Blindness Senior Scientific Investigator Award; Falk Foundation; Massachusetts Lions Eye Research Fund FX This study was supported by NIH grants EY013124, EY021558, and EY014104, a Research to Prevent Blindness Senior Scientific Investigator Award (to J.C.), the Falk Foundation, and the Massachusetts Lions Eye Research Fund. NR 48 TC 9 Z9 10 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2013 VL 4 IS 2 AR e00595-12 DI 10.1128/mBio.00595-12 PG 7 WC Microbiology SC Microbiology GA 137JI UT WOS:000318431500042 PM 23572555 ER PT J AU Blouin, AM Fried, I Wilson, CL Staba, RJ Behnke, EJ Lam, HA Maidment, NT Karlsson, KAE Lapierre, JL Siegel, JM AF Blouin, Ashley M. Fried, Itzhak Wilson, Charles L. Staba, Richard J. Behnke, Eric J. Lam, Hoa A. Maidment, Nigel T. Karlsson, Karl A. E. Lapierre, Jennifer L. Siegel, Jerome M. TI Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction SO NATURE COMMUNICATIONS LA English DT Article ID IN-VIVO MICRODIALYSIS; SLEEP-WAKING CYCLE; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE; NARCOLEPTIC DOGS; OREXIN NEURONS; REM-SLEEP; CATAPLEXY; NUCLEUS; RELEASE AB The neurochemical changes underlying human emotions and social behaviour are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 and melanin-concentrating hormone, measured in the human amygdala. We show that hypocretin-1 levels are maximal during positive emotion, social interaction and anger, behaviours that induce cataplexy in human narcoleptics. In contrast, melanin-concentrating hormone levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. Melanin-concentrating hormone levels increase at sleep onset, consistent with a role in sleep induction, whereas hypocretin-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized. C1 [Blouin, Ashley M.; Lam, Hoa A.; Maidment, Nigel T.; Karlsson, Karl A. E.; Lapierre, Jennifer L.; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Blouin, Ashley M.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Fried, Itzhak; Behnke, Eric J.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. [Fried, Itzhak; Wilson, Charles L.; Maidment, Nigel T.; Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Wilson, Charles L.; Staba, Richard J.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Karlsson, Karl A. E.] Reykjavik Univ, Sch Sci & Engn, IS-101 Reykjavik, Iceland. [Siegel, Jerome M.] Vet Adm Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM JSiegel@ucla.edu FU NIH [MH064109, NS14610, NS33310, NS02808]; Medical Research Service of the Department of Veterans Affairs FX These studies were supported by NIH Grants MH064109, NS14610, NS33310 and NS02808, and the Medical Research Service of the Department of Veterans Affairs. We thank Joyel Alamajano, Grace Barber, Josephine Ruidera and Sandeep Sood for assistance with sample collection, and Larry Ackerson, Tony Fields, Jo Hsieh, Yuval Nir, Ronald McGregor, Lalini Ramanathan and M.F. Wu for technical assistance. NR 58 TC 74 Z9 76 U1 2 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2013 VL 4 AR 1547 DI 10.1038/ncomms2461 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143NJ UT WOS:000318873900001 PM 23462990 ER PT J AU Permuth-Wey, J Lawrenson, K Shen, HC Velkova, A Tyrer, JP Chen, ZH Lin, HY Chen, YA Tsai, YY Qu, XT Ramus, SJ Karevan, R Lee, J Lee, N Larson, MC Aben, KK Anton-Culver, H Antonenkova, N Antoniou, AC Armasu, SM Bacot, F Baglietto, L Bandera, EV Barnholtz-Sloan, J Beckmann, MW Birrer, MJ Bloom, G Bogdanova, N Brinton, LA Brooks-Wilson, A Brown, R Butzow, R Cai, QY Campbell, I Chang-Claude, J Chanock, S Chenevix-Trench, G Cheng, JQ Cicek, MS Coetzee, GA Cook, LS Couch, FJ Cramer, DW Cunningham, JM Dansonka-Mieszkowska, A Despierre, E Doherty, JA Dork, T du Bois, A Durst, M Easton, DF Eccles, D Edwards, R Ekici, AB Fasching, PA Fenstermacher, DA Flanagan, JM Garcia-Closas, M Gentry-Maharaj, A Giles, GG Glasspool, RM Gonzalez-Bosquet, J Goodman, MT Gore, M Gorski, B Gronwald, J Hall, P Halle, MK Harter, P Heitz, F Hillemanns, P Hoatlin, M Hogdall, CK Hogdall, E Hosono, S Jakubowska, A Jensen, A Jim, H Kalli, KR Karlan, BY Kaye, SB Kelemen, LE Kiemeney, LA Kikkawa, F Konecny, GE Krakstad, C Kjaer, SK Kupryjanczyk, J Lambrechts, D Lambrechts, S Lancaster, JM Le, ND Leminen, A Levine, DA Liang, D Lim, BK Lin, J Lissowska, J Lu, KH Lubinski, J Lurie, G Massuger, LFAG Matsuo, K McGuire, V McLaughlin, JR Menon, U Modugno, F Moysich, KB Nakanishi, T Narod, SA Nedergaard, L Ness, RB Nevanlinna, H Nickels, S Noushmehr, H Odunsi, K Olson, SH Orlow, I Paul, J Pearce, CL Pejovic, T Pelttari, LM Pike, MC Poole, EM Raska, P Renner, SP Risch, HA Rodriguez-Rodriguez, L Rossing, MA Rudolph, A Runnebaum, IB Rzepecka, IK Salvesen, HB Schwaab, I Severi, G Shridhar, V Shu, XO Shvetsov, YB Sieh, W Song, HL Southey, MC Spiewankiewicz, B Stram, D Sutphen, R Teo, SH Terry, KL Tessier, DC Thompson, PJ Tworoger, SS van Altena, AM Vergote, I Vierkant, RA Vincent, D Vitonis, AF Wang-Gohrke, S Weber, RP Wentzensen, N Whittemore, AS Wik, E Wilkens, LR Winterhoff, B Woo, YL Wu, AH Xiang, YB Yang, HP Zheng, W Ziogas, A Zulkifli, F Phelan, CM Iversen, E Schildkraut, JM Berchuck, A Fridley, BL Goode, EL Pharoah, PDP Monteiro, ANA Sellers, TA Gayther, SA AF Permuth-Wey, Jennifer Lawrenson, Kate Shen, Howard C. Velkova, Aneliya Tyrer, Jonathan P. Chen, Zhihua Lin, Hui-Yi Chen, Y. Ann Tsai, Ya-Yu Qu, Xiaotao Ramus, Susan J. Karevan, Rod Lee, Janet Lee, Nathan Larson, Melissa C. Aben, Katja K. Anton-Culver, Hoda Antonenkova, Natalia Antoniou, Antonis C. Armasu, Sebastian M. Bacot, Francois Baglietto, Laura Bandera, Elisa V. Barnholtz-Sloan, Jill Beckmann, Matthias W. Birrer, Michael J. Bloom, Greg Bogdanova, Natalia Brinton, Louise A. Brooks-Wilson, Angela Brown, Robert Butzow, Ralf Cai, Qiuyin Campbell, Ian Chang-Claude, Jenny Chanock, Stephen Chenevix-Trench, Georgia Cheng, Jin Q. Cicek, Mine S. Coetzee, Gerhard A. Cook, Linda S. Couch, Fergus J. Cramer, Daniel W. Cunningham, Julie M. Dansonka-Mieszkowska, Agnieszka Despierre, Evelyn Doherty, Jennifer A. Doerk, Thilo du Bois, Andreas Duerst, Matthias Easton, Douglas F. Eccles, Diana Edwards, Robert Ekici, Arif B. Fasching, Peter A. Fenstermacher, David A. Flanagan, James M. Garcia-Closas, Montserrat Gentry-Maharaj, Aleksandra Giles, Graham G. Glasspool, Rosalind M. Gonzalez-Bosquet, Jesus Goodman, Marc T. Gore, Martin Gorski, Bohdan Gronwald, Jacek Hall, Per Halle, Mari K. Harter, Philipp Heitz, Florian Hillemanns, Peter Hoatlin, Maureen Hogdall, Claus K. Hogdall, Estrid Hosono, Satoyo Jakubowska, Anna Jensen, Allan Jim, Heather Kalli, Kimberly R. Karlan, Beth Y. Kaye, Stanley B. Kelemen, Linda E. Kiemeney, Lambertus A. Kikkawa, Fumitaka Konecny, Gottfried E. Krakstad, Camilla Kjaer, Susanne Kruger Kupryjanczyk, Jolanta Lambrechts, Diether Lambrechts, Sandrina Lancaster, Johnathan M. Le, Nhu D. Leminen, Arto Levine, Douglas A. Liang, Dong Lim, Boon Kiong Lin, Jie Lissowska, Jolanta Lu, Karen H. Lubinski, Jan Lurie, Galina Massuger, Leon F. A. G. Matsuo, Keitaro McGuire, Valerie McLaughlin, John R. Menon, Usha Modugno, Francesmary Moysich, Kirsten B. Nakanishi, Toru Narod, Steven A. Nedergaard, Lotte Ness, Roberta B. Nevanlinna, Heli Nickels, Stefan Noushmehr, Houtan Odunsi, Kunle Olson, Sara H. Orlow, Irene Paul, James Pearce, Celeste L. Pejovic, Tanja Pelttari, Liisa M. Pike, Malcolm C. Poole, Elizabeth M. Raska, Paola Renner, Stefan P. Risch, Harvey A. Rodriguez-Rodriguez, Lorna Rossing, Mary Anne Rudolph, Anja Runnebaum, Ingo B. Rzepecka, Iwona K. Salvesen, Helga B. Schwaab, Ira Severi, Gianluca Shridhar, Viji Shu, Xiao-Ou Shvetsov, Yurii B. Sieh, Weiva Song, Honglin Southey, Melissa C. Spiewankiewicz, Beata Stram, Daniel Sutphen, Rebecca Teo, Soo-Hwang Terry, Kathryn L. Tessier, Daniel C. Thompson, Pamela J. Tworoger, Shelley S. van Altena, Anne M. Vergote, Ignace Vierkant, Robert A. Vincent, Daniel Vitonis, Allison F. Wang-Gohrke, Shan Weber, Rachel Palmieri Wentzensen, Nicolas Whittemore, Alice S. Wik, Elisabeth Wilkens, Lynne R. Winterhoff, Boris Woo, Yin Ling Wu, Anna H. Xiang, Yong-Bing Yang, Hannah P. Zheng, Wei Ziogas, Argyrios Zulkifli, Famida Phelan, Catherine M. Iversen, Edwin Schildkraut, Joellen M. Berchuck, Andrew Fridley, Brooke L. Goode, Ellen L. Pharoah, Paul D. P. Monteiro, Alvaro N. A. Sellers, Thomas A. Gayther, Simon A. CA Australian Canc Study Australian Ovarian Canc Study Consortium Investigators Modifiers TI Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31 SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; MICRORNA EXPRESSION; GENETIC-VARIANTS; FUNCTIONAL ANNOTATION; SITE POLYMORPHISMS; PARKINSON-DISEASE; COMMON INVERSION; BINDING-SITES; MAPT REGION; RISK AB Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio 1.12, P 10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P 10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARH-GAP27 and PLEKHM1 as candidate EOC susceptibility genes. C1 [Permuth-Wey, Jennifer; Velkova, Aneliya; Tsai, Ya-Yu; Phelan, Catherine M.; Monteiro, Alvaro N. A.; Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33612 USA. [Lawrenson, Kate; Shen, Howard C.; Ramus, Susan J.; Karevan, Rod; Lee, Janet; Lee, Nathan; Pearce, Celeste L.; Pike, Malcolm C.; Stram, Daniel; Wu, Anna H.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Tyrer, Jonathan P.; Song, Honglin] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England. [Chen, Zhihua; Qu, Xiaotao; Bloom, Greg; Fenstermacher, David A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biomed Informat, Tampa, FL 33612 USA. [Lin, Hui-Yi; Chen, Y. Ann] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biostat, Tampa, FL 33612 USA. [Larson, Melissa C.; Armasu, Sebastian M.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Aben, Katja K.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6500 HB Nijmegen, Netherlands. [Aben, Katja K.; Kiemeney, Lambertus A.] Comprehens Canc Ctr Netherlands, NL-1066 CX Amsterdam, Netherlands. [Anton-Culver, Hoda] Univ Calif Irvine, UCI Ctr Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92697 USA. [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk 223040, Byelarus. [Antoniou, Antonis C.; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Chenevix-Trench, Georgia] Queensland Inst Med Res, Canc Genet Lab, Brisbane, Qld 4006, Australia. [Campbell, Ian] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic 3002, Australia. [Bacot, Francois; Tessier, Daniel C.; Vincent, Daniel] McGill Univ, Montreal, PQ H3A 0G1, Canada. [Bacot, Francois; Tessier, Daniel C.; Vincent, Daniel] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada. [Baglietto, Laura; Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia. [Baglietto, Laura; Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Bandera, Elisa V.; Rodriguez-Rodriguez, Lorna] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08901 USA. [Barnholtz-Sloan, Jill; Raska, Paola] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Beckmann, Matthias W.; Fasching, Peter A.; Renner, Stefan P.] Univ Erlangen Nurnberg, Ctr Comprehens Canc, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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RP Permuth-Wey, J (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33612 USA. EM Jenny.Wey@moffitt.org; Thomas.Sellers@moffitt.org; gayther@usc.edu RI salvesen, Helga/C-1187-2017; Osorio, Ana/I-4324-2014; Wyld, David/B-8893-2015; Jakubowska, Anna/O-8050-2014; campbell, Ian/F-6006-2011; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; montagna, marco/E-2225-2012; Woo, Yin Ling/B-5198-2010; KIKKAWA, Fumitaka/I-7341-2014; Nicklin, James/F-8035-2013; van Altena, Anne/B-9824-2016; Aben, Katja/G-9686-2016; Bowtell, David/H-1007-2016; Gronwald, Jacek/A-4576-2017; Massuger, Leon/H-8072-2014; friedlander, michael/G-3490-2013; Noushmehr, Houtan/C-9692-2013; McLaughlin, John/E-4577-2013; Kiemeney, Lambertus/D-3357-2009; Tang, Macy/B-9798-2014; Blanco, Ignacio/D-2565-2013; Renner, Stefan/F-1158-2014; Dork, Thilo/J-8620-2012; Whittemore, Alice/F-9925-2014; Brooks-Wilson, Angela/E-9399-2012; Teo, Soo-hwang/H-2353-2014; Bandera, Elisa/M-4169-2014 OI Ramus, Susan/0000-0003-0005-7798; Lissowska, Jolanta/0000-0003-2695-5799; Nevanlinna, Heli/0000-0002-0916-2976; Halle, Mari/0000-0002-2660-8271; Orlow, Irene/0000-0001-6234-6961; Krakstad, Camilla/0000-0002-0174-8139; Giles, Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314; salvesen, Helga/0000-0002-4438-8831; Tworoger, Shelley/0000-0002-6986-7046; Osorio, Ana/0000-0001-8124-3984; Nathanson, Katherine/0000-0002-6740-0901; Rudolph, Anja/0000-0001-7520-2035; Kjaer, Susanne/0000-0002-8347-1398; Glasspool, Rosalind/0000-0002-5000-1680; Wyld, David/0000-0001-9523-4333; Monteiro, Alvaro/0000-0002-8448-4801; Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; montagna, marco/0000-0002-4929-2150; Woo, Yin Ling/0000-0003-1742-1066; Nicklin, James/0000-0001-5378-496X; Aben, Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525; Gronwald, Jacek/0000-0002-3643-2871; friedlander, michael/0000-0002-6488-0604; Noushmehr, Houtan/0000-0003-4051-8114; Kiemeney, Lambertus/0000-0002-2368-1326; Blanco, Ignacio/0000-0002-7414-7481; Renner, Stefan/0000-0003-2057-1268; Brooks-Wilson, Angela/0000-0003-1009-6408; Bandera, Elisa/0000-0002-8789-2755 FU European Commission [223175-HEALTH-F2-2009-223175]; Ovarian Cancer Research Fund; US National Cancer Institute [R01-CA-114343, R01-CA114343-S1]; Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative [U19-CA148112]; Wellcome Trust [076113]; National Health and Medical Research Council; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; Canadian Institutes of Health Research [MSH-87734]; NHS; American Cancer Society [CRTG-00-196-01-CCE]; California Cancer Research Program [00-01389V-20170, N01-CN25403, 2II0200]; Canadian Institutes for Health Research [MOP-86727]; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; Cancer Institute of New Jersey; Cancer Research UK [C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689]; Celma Mastry Ovarian Cancer Foundation; Danish Cancer Society [94-222-52]; Norwegian Cancer Society, Helse Vest, the Norwegian Research Council; ELAN Funds of the University of Erlangen-Nuremberg; Eve Appeal; Helsinki University Central Hospital Research Fund; Imperial Experimental Cancer Research Centre [C1312/A15589]; Nationaal Kankerplan of Belgium; Ministry of Health Labour and Welfare of Japan; L & S Milken Foundation; Radboud University Nijmegen Medical Centre; Polish Ministry of Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Roswell Park Cancer Institute Alliance Foundation; US National Cancer Institutes [K07-CA80668, K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067001, N01-PC035137, P01-CA017054, P01-CA087696, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419]; NIH/National Center for Research Resources/General Clinical Research Grant [M01-RR000056]; US Army Medical Research and Materiel Command [DAMD17-98-18659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-101-02802]; Department of Defense Ovarian Cancer Research Program [W81XWH-07-1-0449]; National Health and Medical Research Council of Australia [199600, 400281]; German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]; German Cancer Research Center; Pomeranian Medical University; Minnesota Ovarian Cancer Alliance; Mayo Foundation; Fred C. and Katherine B. Andersen Foundation; Malaysian Ministry of Higher Education [UM. C/HlR/MOHE/06]; Cancer Research Initiatives Foundation; Lon V. Smith Foundation [LVS-39420]; Oak Foundation; OHSU Foundation; Mermaid I project; Rudolf-Bartling Foundation; UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; Imperial College London; University College Hospital 'Womens Health Theme'; Royal Marsden Hospital; WorkSafeBC; U.S. Natl Canc Inst [R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA136924, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R01-CA83918, U01-CA069417, U01-CA071966, P30-CA15083, PSA 042205] FX We thank all the individuals who participated in this research and all the researchers, clinicians and administrative staff who have made possible the many studies contributing to this work. In particular, we thank D. Bowtell, P. Webb, A. deFazio, D. Gertig, A. Green, P. Parsons, N. Hayward and D. Whiteman (AUS); D. L. Wachter, S. Oeser, S. Landrith (BAV); G. Peuteman, T. Van Brussel and D. Smeets (BEL); the staff of the genotyping unit, S LaBoissiere and F Robidoux (McGill University and Genome Quebec Innovation Centre); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P. Schuermann, F. Kramer, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (HJO); G. L. Keeney, C. Hilker and J. Vollenweider (MAY); the state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL, GA, HI, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WYL (NHS); L. Paddock, M. King, U. Chandran, A. Samoila and Y. Bensman (NJO); M. Insua and R. Evey (Moffitt); The Sherie Hildredth Ovarian Cancer Foundation (ORE); M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (POL); C. Luccarini, P. Harrington the SEARCH team and ECRIC (SEA); the Scottish Gynaecological Clinical Trails group and SCOTROC1 investigators (SRO); W-H. Chow, Y.-T. Gao, G. Yang, B.-T. Ji (SWH); I. Jacobs, M. Widschwendter, E. Wozniak, N. Balogun, A. Ryan and J. Ford (UKO); M. Notaridou (USC); C. Pye (UKR); and V. Slusher (U19). The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175-HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund, thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07).; The scientific development and funding for this project were in part supported by the US National Cancer Institute (R01-CA-114343 and R01-CA114343-S1) and the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112). This study made use of the data generated by the Wellcome Trust Case Control consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute. Information about TCGA, and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/. D. F. E. is a Principal Research Fellow of Cancer Research UK, G.C.-T. and P. M. W. are supported by the National Health and Medical Research Council. B. K. holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). L. E. K. is supported by a Canadian Institutes of Health Research Investigator award (MSH-87734). M. G. acknowledges NHS funding to the NIHR Biomedical Research Centre. A. C. A. is Cancer Research UK Senior Cancer Research Fellow.; Funding of the constituent studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the Norwegian Cancer Society, Helse Vest, the Norwegian Research Council; ELAN Funds of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Imperial Experimental Cancer Research Centre (C1312/A15589); the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L & S Milken Foundation; the Radboud University Nijmegen Medical Centre; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA80668, K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067001, N01-PC035137, P01-CA017054, P01-CA087696, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA136924, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R01-CA83918, U01-CA069417, U01-CA071966, P30-CA15083, PSA 042205, and Intramural research funds); the NIH/National Center for Research Resources/General Clinical Research Grant (M01-RR000056); the US Army Medical Research and Materiel Command (DAMD17-98-18659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-101- 02802); the Department of Defense Ovarian Cancer Research Program (W81XWH-07-1-0449); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the state of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P. 685); the German Cancer Research Center; Pomeranian Medical University; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Malaysian Ministry of Higher Education (UM. C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital 'Womens Health Theme' and the Royal Marsden Hospital; WorkSafeBC. NR 53 TC 49 Z9 49 U1 2 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2013 VL 4 AR 1627 DI 10.1038/ncomms2613 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143NJ UT WOS:000318873900080 PM 23535648 ER PT J AU Mischoulon, D Freeman, MP AF Mischoulon, David Freeman, Marlene P. TI Omega-3 Fatty Acids in Psychiatry SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Omega-3; n-3; Depression; Bipolar disorder; Complementary and alternative medicine; Ethyl-eicosapentaenoate; Docosahexaenoic acid ID METAANALYSIS; DEPRESSION; TRIALS; MOOD AB Over the past 2 decades, omega-3 fatty acids (n-3FAs) have been increasingly used and studied in the United States and worldwide for various medical and psychiatric indications. Numerous published clinical trials have examined applications of different n-3FA preparations, primarily in mood disorders but also in psychotic disorders, attention-deficit disorder, obsessive-compulsive disorder, and personality disorders. Focusing on clinical issues, this article reviews the impact of n-3FAs on these conditions and covers the relevant research, side effects, dosage guidelines, and drug interactions; clinicians should thus be able to better advise patients who are already taking n-3FAs or are interested in trying them. C1 [Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. [Mischoulon, David; Freeman, Marlene P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Freeman, Marlene P.] Harvard Univ, Perinatal & Reprod Psychiat Program, Sch Med, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org NR 10 TC 11 Z9 11 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 2013 VL 36 IS 1 BP 15 EP + DI 10.1016/j.psc.2012.12.002 PG 10 WC Psychiatry SC Psychiatry GA 145PN UT WOS:000319029400003 PM 23538073 ER PT J AU Sadatsafavi, M Bansback, N Zafari, Z Najafzadeh, M Marra, C AF Sadatsafavi, Mohsen Bansback, Nick Zafari, Zafar Najafzadeh, Mehdi Marra, Carlo TI Need for Speed: An Efficient Algorithm for Calculation of Single-Parameter Expected Value of Partial Perfect Information SO VALUE IN HEALTH LA English DT Article DE Bayesian analysis; decision uncertainty; medical decision making; value of information ID SAMPLE INFORMATION; DECISION; MODELS AB Background: The expected value of partial perfect information (EVPPI) is a theoretically justifiable and informative measure of uncertainty in decision-analytic cost-effectiveness models, but its calculation is computationally intensive because it generally requires two-level Monte Carlo simulation. We introduce an efficient, one-level simulation method for the calculation of single-parameter EVPPI. Objective: We show that under mild regularity assumptions, the expectation-maximization-expectation sequence in EVPPI calculation can be transformed into an expectation-maximization-maximization sequence. By doing so, calculations can be performed in a single-step expectation by using data generated for probabilistic sensitivity analysis. We prove that the proposed estimator of EVPPI converges in probability to the true EVPPI. Methods and Results: The performance of the new method was empirically demonstrated by using three exemplary decision models. Our proposed method seems to achieve remarkably higher accuracy than the two-level method with a fraction of its computation costs, though the achievement in accuracy was not uniform and varied across the parameters of the models. Software is provided to calculate single-parameter EVPPI based on the probabilistic sensitivity analysis data. Conclusions: The new method, though applicable only to single-parameter EVPPI, is fast, accurate, and easy to implement. Further research is needed to evaluate the performance of this method in more complex scenarios and to extend such a concept to similar measures of decision uncertainty. C1 [Sadatsafavi, Mohsen] Univ British Columbia, Dept Med, Vancouver, BC V6T 1Z3, Canada. [Sadatsafavi, Mohsen; Zafari, Zafar; Najafzadeh, Mehdi; Marra, Carlo] Univ British Columbia, Collaborat Outcomes Res & Evaluat, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada. [Sadatsafavi, Mohsen] Univ British Columbia, Vancouver Coastal Hlth Inst, Ctr Clin Epidemiol & Evaluat, Vancouver, BC V6T 1Z3, Canada. [Bansback, Nick] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada. [Najafzadeh, Mehdi] Harvard Univ, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02115 USA. RP Sadatsafavi, M (reprint author), Univ British Columbia, Fac Med, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada. EM sadatsafavi@alumni.ubc.ca FU Canadian Institute of Health Research [200889] FX M.S. was funded by a Canadian Institute of Health Research fellowship award (#200889) during this work. The authors express no apparent or perceived conflict of interest. NR 10 TC 12 Z9 12 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAR-APR PY 2013 VL 16 IS 2 BP 438 EP 448 DI 10.1016/j.jval.2012.10.018 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 144AC UT WOS:000318910400025 PM 23538197 ER PT J AU Wang, YF Velho, S Vakiani, E Peng, SY Bass, AJ Chu, GC Gierut, J Bugni, JM Der, CJ Philips, M Solit, DB Haigis, KM AF Wang, Yufang Velho, Sergia Vakiani, Efsevia Peng, Shouyong Bass, Adam J. Chu, Gerald C. Gierut, Jessica Bugni, James M. Der, Channing J. Philips, Mark Solit, David B. Haigis, Kevin M. TI Mutant N-RAS Protects Colorectal Cancer Cells from Stress-Induced Apoptosis and Contributes to Cancer Development and Progression SO CANCER DISCOVERY LA English DT Article ID ONCOGENIC K-RAS; PHOSPHOINOSITIDE 3-KINASE; TUMOR PROGRESSION; DRUG-SENSITIVITY; RNA INTERFERENCE; CARCINOMA CELLS; COLON-CANCER; H-RAS; ACTIVATION; KINASE AB N-RAS is one member of a family of oncoproteins that are commonly mutated in cancer. Activating mutations in NRAS occur in a subset of colorectal cancers, but little is known about how the mutant protein contributes to the onset and progression of the disease. Using genetically engineered mice, we find that mutant N-RAS strongly promotes tumorigenesis in the context of inflammation. The protumorigenic nature of mutant N-RAS is related to its antiapoptotic function, which is mediated by activation of a noncanonical mitogen-activated protein kinase pathway that signals through STAT3. As a result, inhibition of MAP-ERK kinase selectively induces apoptosis in autochthonous colonic tumors expressing mutant N-RAS. The translational significance of this finding is highlighted by our observation that NRAS mutation correlates with a less favorable clinical outcome for patients with colorectal cancer. These data show for the first time the important role that N-RAS plays in colorectal cancer. SIGNIFICANCE: Little is known about N-RAS function in normal biology or in cancer. Our study links the antiapoptotic function of mutant N-RAS to its ability to promote colorectal cancer in an inflammatory context. In addition, our study pinpoints a therapeutic strategy for this distinct colorectal cancer subtype. Cancer Discov; 3(3); 294-307. (C) 2013 AACR. C1 [Wang, Yufang; Velho, Sergia; Gierut, Jessica; Haigis, Kevin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Pathol Unit,Ctr Canc Res, Charlestown, MA USA. [Wang, Yufang; Velho, Sergia; Gierut, Jessica; Haigis, Kevin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA USA. [Peng, Shouyong; Bass, Adam J.; Chu, Gerald C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Peng, Shouyong; Bass, Adam J.; Chu, Gerald C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Bass, Adam J.; Chu, Gerald C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Chu, Gerald C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Vakiani, Efsevia] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Philips, Mark] NYU, Sch Med, Inst Canc, New York, NY USA. [Bugni, James M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Inflammatory Bowel Dis Ctr, Los Angeles, CA 90095 USA. [Der, Channing J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Der, Channing J.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA. RP Haigis, KM (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149 13th St,7-372, Charlestown, MA 02129 USA. EM khaigis@partners.org RI Velho, Sergia/B-8501-2013 OI Velho, Sergia/0000-0002-7104-8234 FU Portuguese Fundacao para a Ciencia e a Tecnologia; National Cancer Institute [CA118425]; Massachusetts General Hospital Center for the Study of Inflammatory Bowel Disease [DK043351] FX S. Velho is supported by a postdoctoral fellowship from the Portuguese Fundacao para a Ciencia e a Tecnologia. K. M. Haigis was supported by a grant from the National Cancer Institute (CA118425) and by a Pilot Feasibility Award from the Massachusetts General Hospital Center for the Study of Inflammatory Bowel Disease (DK043351). NR 50 TC 19 Z9 22 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2013 VL 3 IS 3 BP 294 EP 307 DI 10.1158/2159-8290.CD-12-0198 PG 14 WC Oncology SC Oncology GA 126FP UT WOS:000317598500014 PM 23274911 ER PT J AU Puissant, A Frumm, SM Alexe, G Bassil, CF Qi, J Chanthery, YH Nekritz, EA Zeid, R Gustafson, WC Greninger, P Garnett, MJ McDermott, U Benes, CH Kung, AL Weiss, WA Bradner, JE Stegmaier, K AF Puissant, Alexandre Frumm, Stacey M. Alexe, Gabriela Bassil, Christopher F. Qi, Jun Chanthery, Yvan H. Nekritz, Erin A. Zeid, Rhamy Gustafson, William Clay Greninger, Patricia Garnett, Matthew J. McDermott, Ultan Benes, Cyril H. Kung, Andrew L. Weiss, William A. Bradner, James E. Stegmaier, Kimberly TI Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition SO CANCER DISCOVERY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ANAPLASTIC LYMPHOMA KINASE; ACUTE MYELOID-LEUKEMIA; CELL LUNG-CANCER; ACTIVATING MUTATIONS; THERAPEUTIC TARGET; DRUG-SENSITIVITY; ALK KINASE; N-MYC; C-MYC AB Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis showed downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knockdown phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a signifi cant survival advantage in 3 in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma. SIGNIFICANCE: Biomarkers of response to small-molecule inhibitors of BET bromodomains, a new compound class with promising anticancer activity, have been lacking. Here, we reveal MYCN amplification as a strong genetic predictor of sensitivity to BET bromodomain inhibitors, show a mechanistic rationale for this finding, and provide a translational framework for clinical trial development of BET bromodomain inhibitors for pediatric patients with MYCN-amplified neuroblastoma. Cancer Discov; 3(3); 308-23. (C) 2012 AACR. C1 [Puissant, Alexandre; Frumm, Stacey M.; Alexe, Gabriela; Bassil, Christopher F.; Kung, Andrew L.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Qi, Jun; Zeid, Rhamy; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Puissant, Alexandre; Frumm, Stacey M.; Alexe, Gabriela; Bassil, Christopher F.; Kung, Andrew L.; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Alexe, Gabriela] Boston Univ, Bioinformat Grad Program, Boston, MA 02215 USA. [Alexe, Gabriela; Stegmaier, Kimberly] Broad Inst Harvard Univ & Massachusetts Inst Tech, Cambridge, MA USA. [Greninger, Patricia; Benes, Cyril H.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA USA. [Chanthery, Yvan H.; Nekritz, Erin A.; Gustafson, William Clay; Weiss, William A.] Helen Diller Family Comprehens Canc Ctr, Dept Pediat, San Francisco, CA USA. [Weiss, William A.] Univ Calif San Francisco, Dept Neurol, Brain Tumor Res Ctr, San Francisco, CA USA. [Weiss, William A.] Univ Calif San Francisco, Dept Neurosurg, Brain Tumor Res Ctr, San Francisco, CA USA. [Garnett, Matthew J.; McDermott, Ultan] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England. RP Stegmaier, K (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM james_bradner@dfci.harvard.edu; kimberly_stegmaier@dfci.harvard.edu RI PUISSANT, ALEXANDRE/O-9575-2016; OI PUISSANT, ALEXANDRE/0000-0002-3997-9282; McDermott, Ultan/0000-0001-9032-4700; Kung, Andrew/0000-0002-9091-488X; Weiss, William/0000-0003-2230-9132 FU V Foundation for Cancer Research Translational Grant; Friends for Life Fellowship; Howard Hughes Medical Institute Physician-Scientist Early Career Award; Damon Runyon Cancer Research Foundation; Smith Family Foundation; Alex's Lemonade Stand; NIH [R01CA102321, P01CA081403, K08NS079485, T32CA151022]; Wellcome Trust [086357]; Katie Dougherty Foundation; Cancer League, Inc.; Samuel Waxman Cancer Research Foundation; L'Association pour la Recherche sur le Cancer; Stand Up to Cancer Innovative Research Grant, a Program of the Entertainment Industry Foundation [SU2C-AACR-IRG0509] FX This study was supported by V Foundation for Cancer Research Translational Grant (to K. Stegmaier and J.E. Bradner); Friends for Life Fellowship (to K. Stegmaier and A. L. Kung); Howard Hughes Medical Institute Physician-Scientist Early Career Award (to K. Stegmaier); Damon Runyon Cancer Research Foundation and Smith Family Foundation (to J.E. Bradner and J. Qi); Alex's Lemonade Stand (to W. C. Gustafson); NIH grants R01CA102321 (to W. A. Weiss), P01CA081403 (to W. A. Weiss), K08NS079485 (to W. C. Gustafson), and T32CA151022 (to Y.H. Chanthery); The Wellcome Trust (086357; to U. McDermott, M. J. Garnett, P. Greninger, and C. H. Benes); The Katie Dougherty Foundation (to W. A. Weiss); The Cancer League, Inc. (to W. A. Weiss); the Samuel Waxman Cancer Research Foundation (to J. E. Bradner and W. A. Weiss); and L'Association pour la Recherche sur le Cancer (to A. Puissant). K. Stegmaier is also supported by a Stand Up to Cancer Innovative Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-IRG0509). NR 50 TC 177 Z9 180 U1 7 U2 37 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2013 VL 3 IS 3 BP 308 EP 323 DI 10.1158/2159-8290.CD-12-0418 PG 16 WC Oncology SC Oncology GA 126FP UT WOS:000317598500015 PM 23430699 ER PT J AU He, L Torres-Lockhart, K Forster, N Ramakrishnan, S Greninger, P Garnett, MJ McDermott, U Rothenberg, SM Benes, CH Ellisen, LW AF He, Lei Torres-Lockhart, Kristine Forster, Nicole Ramakrishnan, Saranya Greninger, Patricia Garnett, Mathew J. McDermott, Ultan Rothenberg, Stephen M. Benes, Cyril H. Ellisen, Leif W. TI Mcl-1 and FBW7 Control a Dominant Survival Pathway Underlying HDAC and Bcl-2 Inhibitor Synergy in Squamous Cell Carcinoma SO CANCER DISCOVERY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BH3 MIMETIC ABT-737; NECK-CANCER; DRUG-SENSITIVITY; TUMOR-SUPPRESSOR; HEAD; APOPTOSIS; VORINOSTAT; EXPRESSION; PREDICTS AB Effective targeted therapeutics for squamous cell carcinoma (SCC) are lacking. Here, we uncover Mcl-1 as a dominant and tissue-specific survival factor in SCC, providing a roadmap for a new therapeutic approach. Treatment with the histone deacetylase (HDAC) inhibitor vorinostat regulates Bcl-2 family member expression to disable the Mcl-1 axis and thereby induce apoptosis in SCC cells. Although Mcl-1 dominance renders SCC cells resistant to the BH3-mimetic ABT-737, vorinostat primes them for sensitivity to ABT-737 by shuttling Bim from Mcl-1 to Bcl-2/Bcl-xl, resulting in dramatic synergy for this combination and sustained tumor regression in vivo. Moreover, somatic FBW7 mutation in SCC is associated with stabilized Mcl-1 and high Bim levels, resulting in a poor response to standard chemotherapy but a robust response to HDAC inhibitors and enhanced synergy with the combination vorinostat/ABT-737. Collectively, our findings provide a biochemical rationale and predictive markers for the application of this therapeutic combination in SCC. SIGNIFICANCE: This study reveals the tissue-specific landscape and biochemistry of the Bcl-2 family in SCC, which underlie moderate sensitivity of these tumors to HDAC inhibitor therapy but dramatic synergy in combination with BH3-mimetic therapy. By establishing predictive biomarkers, we provide evidence that tumors most likely to respond to this therapeutic combination, including those harboring somatic FBW7 mutations, are those most resistant to standard chemotherapy. Cancer Discov; 3(3); 324-37. (C) 2012 AACR. C1 [He, Lei; Torres-Lockhart, Kristine; Forster, Nicole; Ramakrishnan, Saranya; Greninger, Patricia; Rothenberg, Stephen M.; Benes, Cyril H.; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [He, Lei; Torres-Lockhart, Kristine; Forster, Nicole; Ramakrishnan, Saranya; Greninger, Patricia; Rothenberg, Stephen M.; Benes, Cyril H.; Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA USA. [Garnett, Mathew J.; McDermott, Ultan] Wellcome Trust Sanger Inst, Cambridge, England. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ 904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu OI McDermott, Ultan/0000-0001-9032-4700 FU National Institute of Dental and Craniofacial Research [RO1 DE015945]; Congressionally Directed Medical Research Programs/Breast Cancer Research Program [BC093523]; Deutsche Forschungsgemeinschaft (German Research Foundation) [FO 785/1-2]; NIH [KO8 DE-020139]; Wellcome Trust [086357] FX This work was supported by grants National Institute of Dental and Craniofacial Research RO1 DE015945 (to L. W. Ellisen, K. Torres-Lockhart, and S. Ramakrishnan), Congressionally Directed Medical Research Programs/Breast Cancer Research Program BC093523 (to L. He), Deutsche Forschungsgemeinschaft (German Research Foundation) FO 785/1-2 (to N. Forster), and NIH KO8 DE-020139 (to S. M. Rothenberg), and by a grant from the Wellcome Trust (086357; to P. Greninger, U. McDermott, M.J. Garnett, and C. H. Benes). NR 42 TC 22 Z9 23 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2013 VL 3 IS 3 BP 324 EP 337 DI 10.1158/2159-8290.CD-12-0417 PG 14 WC Oncology SC Oncology GA 126FP UT WOS:000317598500016 PM 23274910 ER PT J AU Maertens, O Johnson, B Hollstein, P Frederick, DT Cooper, ZA Messiaen, L Bronson, RT McMahon, M Granter, S Flaherty, K Wargo, JA Marais, R Cichowski, K AF Maertens, Ophelia Johnson, Bryan Hollstein, Pablo Frederick, Dennie T. Cooper, Zachary A. Messiaen, Ludwine Bronson, Roderick T. McMahon, Martin Granter, Scott Flaherty, Keith Wargo, Jennifer A. Marais, Richard Cichowski, Karen TI Elucidating Distinct Roles for NF1 in Melanomagenesis SO CANCER DISCOVERY LA English DT Article ID ONCOGENE-INDUCED SENESCENCE; RAF INHIBITOR RESISTANCE; CELL-CYCLE ARREST; TUMOR-SUPPRESSOR; B-RAF; MALIGNANT-MELANOMA; SOMATIC MUTATIONS; BRAF MUTATIONS; HIGH-FREQUENCY; PATHWAY AB BRAF mutations play a well-established role in melanomagenesis; however, without additional genetic alterations, tumor development is restricted by oncogene-induced senescence (OIS). Here, we show that mutations in the NF1 tumor suppressor gene cooperate with BRAF mutations in melanomagenesis by preventing OIS. In a genetically engineered mouse model, Nf1 mutations suppress Braf-induced senescence, promote melanocyte hyperproliferation, and enhance melanoma development. Nf1 mutations function by deregulating both phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways. As such, Nf1/Braf-mutant tumors are resistant to BRAF inhibitors but are sensitive to combined inhibition of mitogen-activated protein/extracellular signal-regulated kinase kinase and mTOR. Importantly, NF1 is mutated or suppressed in human melanomas that harbor concurrent BRAF mutations, NF1 ablation decreases the sensitivity of melanoma cell lines to BRAF inhibitors, and NF1 is lost in tumors from patients following treatment with these agents. Collectively, these studies provide mechanistic insight into how NF1 cooperates with BRAF mutations in melanoma and show that NF1/neurofibromin inactivation may have an impact on responses to targeted therapies. SIGNIFICANCE: This study elucidates the mechanism by which NF1 mutations cooperate with different BRAF mutations in melanomagenesis and shows that NF1/neurofibromin loss may desensitize tumors to BRAF inhibitors. Cancer Discov; 3(3); 338-49. (C) 2012 AACR. C1 [Maertens, Ophelia; Johnson, Bryan; Hollstein, Pablo; Cichowski, Karen] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. [Granter, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Maertens, Ophelia; Johnson, Bryan; Hollstein, Pablo; Bronson, Roderick T.; Granter, Scott; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Frederick, Dennie T.; Cooper, Zachary A.; Flaherty, Keith; Wargo, Jennifer A.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Frederick, Dennie T.; Cooper, Zachary A.; Flaherty, Keith; Wargo, Jennifer A.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Frederick, Dennie T.; Cooper, Zachary A.; Flaherty, Keith; Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Cichowski, Karen] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Messiaen, Ludwine] Univ Alabama Birmingham, Dept Genet, Med Genom Lab, Birmingham, AL USA. [McMahon, Martin] Univ Calif San Francisco, Canc Res Inst, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [McMahon, Martin] Univ Calif San Francisco, Dept Cell & Mol Pharmacol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Marais, Richard] Univ Manchester, Paterson Inst Canc Res, Manchester, Lancs, England. RP Cichowski, K (reprint author), Brigham & Womens Hosp, 77 Ave Louis Pasteur,NRB 0458C, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu OI Marais, Richard/0000-0001-7484-4183; Cooper, Zachary/0000-0003-1059-0940 FU National Cancer Institute [R01 CA111754]; Ludwig Center at Dana-Farber/Harvard Cancer Center; Novartis; Plexxikon FX K. Cichowski and the majority of this work was supported by the National Cancer Institute (R01 CA111754) and the Ludwig Center at Dana-Farber/Harvard Cancer Center. O. Maertens is a postdoctoral fellow of the Research Foundation Flanders (FWO).; M. McMahon has commercial research grants from Novartis and Plexxikon. R. Marais is Secretary General of the European Association for Cancer Research, has received honoraria from service on the speakers' bureau for Roche, and is a consultant/advisory board member for Novartis and Servier Research Institute. No potential conflicts of interest were disclosed by the other authors. NR 57 TC 74 Z9 76 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2013 VL 3 IS 3 BP 338 EP 349 DI 10.1158/2159-8290.CD-12-0313 PG 12 WC Oncology SC Oncology GA 126FP UT WOS:000317598500017 PM 23171796 ER PT J AU Whittaker, SR Theurillat, JP Van Allen, E Wagle, N Hsiao, J Cowley, GS Schadendorf, D Root, DE Garraway, LA AF Whittaker, Steven R. Theurillat, Jean-Philippe Van Allen, Eliezer Wagle, Nikhil Hsiao, Jessica Cowley, Glenn S. Schadendorf, Dirk Root, David E. Garraway, Levi A. TI A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition SO CANCER DISCOVERY LA English DT Article ID ACQUIRED-RESISTANCE; KINASE INHIBITORS; TUMOR PROGRESSION; IMPROVED SURVIVAL; BRAF INHIBITION; MEK INHIBITION; MELANOMA; MUTATIONS; CRAF; PATHWAY AB RAF inhibitors such as vemurafenib and dabrafenib block BRAF-mediated cell proliferation and achieve meaningful clinical benefit in the vast majority of patients with BRAF(V600E)-mutant melanoma. However, some patients do not respond to this regimen, and nearly all progress to therapeutic resistance. We used a pooled RNA interference screen targeting more than 16,500 genes to discover loss-of-function events that could drive resistance to RAF inhibition. The highest ranking gene was NF1, which encodes neurofibromin, a tumor suppressor that inhibits RAS activity. NF1 loss mediates resistance to RAF and mitogen-activated protein kinase (MAPK) kinase kinase (MEK) inhibitors through sustained MAPK pathway activation. However, cells lacking NF1 retained sensitivity to the irreversible RAF inhibitor AZ628 and an ERK inhibitor. NF1 mutations were observed in BRAF-mutant tumor cells that are intrinsically resistant to RAF inhibition and in melanoma tumors obtained from patients exhibiting resistance to vemurafenib, thus showing the clinical potential for NF1-driven resistance to RAF/MEK-targeted therapies. SIGNIFICANCE: This work identifies functional loss of NF1 as a mediator of resistance to RAF inhibitors in BRAF(V600E)-mutant cancers. Furthermore, we nominate new therapeutic modalities to treat this mechanism of resistance. Cancer Discov; 3(3); 350-62. (C) 2012 AACR. C1 [Whittaker, Steven R.; Theurillat, Jean-Philippe; Van Allen, Eliezer; Wagle, Nikhil; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Garraway, Levi A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Whittaker, Steven R.; Theurillat, Jean-Philippe; Van Allen, Eliezer; Wagle, Nikhil; Hsiao, Jessica; Cowley, Glenn S.; Root, David E.; Garraway, Levi A.] Broad Inst, Cambridge, MA USA. [Schadendorf, Dirk] Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM levi_garraway@dfci.harvard.edu OI Van Allen, Eliezer/0000-0002-0201-4444 FU National Cancer Institute [5P50CA127003-05]; STARR Cancer Consortium [I4-A448]; NIH New Innovator Award [DP2OD002750]; Melanoma Research Alliance; Swiss Foundation for Grants in Biology and Medicine [PASMP3_134379/1]; Novartis FX This study was supported by grants from the National Cancer Institute (5P50CA127003-05) STARR Cancer Consortium (I4-A448), the NIH New Innovator Award (DP2OD002750), and the Melanoma Research Alliance. J.-P. Theurillat is supported by the Swiss Foundation for Grants in Biology and Medicine (PASMP3_134379/1).; N. Wagle has an ownership interest (including patents) and is a consultant/advisory board member for Foundation Medicine. G. S. Cowley and D. Schadendorf have received honoraria from service on the speakers' bureaus from MSD, Roche, and Bristol-Myers Squibb and are consultant/advisory board members of Bristol-Myers Squibb, Roche, GlaxoSmithKline, Amgen, and Novartis. L. A. Garraway has a commercial research grant from Novartis, has ownership interest (including patents) in Foundation Medicine, and is a consultant/advisory board member for Millennium/Takeda, Novartis, and Foundation Medicine. No potential conflicts of interest were disclosed by the other authors. NR 44 TC 109 Z9 113 U1 0 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2013 VL 3 IS 3 BP 350 EP 362 DI 10.1158/2159-8290.CD-12-0470 PG 13 WC Oncology SC Oncology GA 126FP UT WOS:000317598500018 PM 23288408 ER PT J AU McNally, JM McCarley, RW Brown, RE AF McNally, James M. McCarley, Robert W. Brown, Ritchie E. TI Impaired GABAergic Neurotransmission in Schizophrenia Underlies Impairments in Cortical Gamma Band Oscillations SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Schizophrenia; Gamma oscillations; Interneurons; Parvalbumin; NMDAR; GAD67; Psychiatry ID NMDA RECEPTOR HYPOFUNCTION; MESSENGER-RNA EXPRESSION; AUDITORY HALLUCINATION SYMPTOMS; FAST-SPIKING CELLS; PREFRONTAL CORTEX; INHIBITORY NEURONS; NEURAL SYNCHRONY; GENE-EXPRESSION; WORKING-MEMORY; IN-VITRO AB Impairment of cortical circuit function is increasingly believed to be central to the pathophysiology of schizophrenia (Sz). Such impairments are suggested to result in abnormal gamma band oscillatory activity observed in Sz patients, and likely underlie the psychosis and cognitive deficits linked to this disease. Development of improved therapeutic strategies to enhance functional outcome of Sz patients is contingent upon a detailed understanding of the mechanisms behind cortical circuit development and maintenance. Convergent evidence from both Sz clinical and preclinical studies suggests impaired activity of a particular subclass of interneuron which expresses the calcium binding protein parvalbumin is central to the cortical circuit impairment observed. Here we review our current understanding of the Sz related cortical circuit dysfunction with a particular focus on the role of fast spiking parvalbumin interneurons in both normal cortical circuit activity and in NMDA receptor hypofunction models of the Sz disease state. C1 [McNally, James M.; McCarley, Robert W.; Brown, Ritchie E.] Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA 02301 USA. [McNally, James M.; McCarley, Robert W.; Brown, Ritchie E.] VA Boston Healthcare Syst, Neurosci Lab, Brockton, MA USA. RP McNally, JM (reprint author), Harvard Univ, Dept Psychiat, Sch Med, VABHS, 940 Belmont St, Brockton, MA 02301 USA. EM james_mcnally@hms.harvard.edu; robert_mccarley@hms.harvard.edu; ritchie_brown@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Brown, Ritchie/0000-0002-7164-4132 FU Department of Veterans Affairs Medical Research Service; National Institutes of Health [MH040799, MH039683, MH094803] FX This work was supported by Department of Veterans Affairs Medical Research Service Awards (R.W. McCarley), and grants from the National Institutes of Health: MH040799 (R.W. McCarley), MH039683 (R.W. McCarley), and MH094803 (R.E. Brown). NR 101 TC 12 Z9 12 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD MAR PY 2013 VL 15 IS 3 AR 346 DI 10.1007/s11920-012-0346-z PG 9 WC Psychiatry SC Psychiatry GA 141XU UT WOS:000318760700004 PM 23400808 ER PT J AU Ripoll, LH Snyder, R Steele, H Siever, LJ AF Ripoll, Luis H. Snyder, Rebekah Steele, Howard Siever, Larry J. TI The Neurobiology of Empathy in Borderline Personality Disorder SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Borderline personality disorder; BPD; Personality; Empathy; Attachment theory; Social cognition; Aggression; Social affectivity; Neuropeptides; Neurobiology; Psychiatry ID REJECTION SENSITIVITY; EMOTION RECOGNITION; SOCIAL EXCLUSION; FACIAL EMOTION; SELF-INJURY; ATTACHMENT; OXYTOCIN; PAIN; FMRI; CHILDHOOD AB We present a neurobiological model of empathic dysfunction in borderline personality disorder (BPD) to guide future empirical research. Empathy is a necessary component of interpersonal functioning, involving two distinct, parallel neural networks. One form of empathic processing relies on shared representations (SR) of others' mental states, while the other is associated with explicit mental state attribution (MSA). SR processing is visceral and automatic, contributing to attunement, but also emotional contagion. MSA processing contributes to deliberate, perspectival forms of empathic understanding. Empathic dysfunction in BPD may involve hyper-reactivity of SR networks and impairment of MSA networks. Nevertheless, this empathic dysfunction is subtle, but contributes to interpersonal difficulties. Interaction between genetic factors and traumatic attachment stressors may contribute to development of BPD, with painful attachment insecurity and disorganization affecting SR and MSA network functioning. Future avenues for BPD research will include developmental assessment of attachment and neurobiological functioning under varying conditions. C1 [Ripoll, Luis H.; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ripoll, Luis H.] New York Psychoanalyt Inst, New York, NY USA. [Snyder, Rebekah] Columbia Univ, Dept Psychol, Barnard Coll, New York, NY 10027 USA. [Steele, Howard] New Sch Social Res, Dept Psychol, New York, NY 10011 USA. [Siever, Larry J.] Mental Illness Res Educ & Clin Ctr MIRECC, James J Peters VA Med Ctr, Bronx, NY USA. RP Ripoll, LH (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM Luis.ripoll@mssm.edu NR 99 TC 13 Z9 14 U1 4 U2 40 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD MAR PY 2013 VL 15 IS 3 AR 344 DI 10.1007/s11920-012-0344-1 PG 11 WC Psychiatry SC Psychiatry GA 141XU UT WOS:000318760700002 PM 23389774 ER PT J AU Miller, MW Wolf, EJ Reardon, AF Harrington, KM Ryabchenko, K Castillo, D Freund, R Heyman, RE AF Miller, Mark W. Wolf, Erika J. Reardon, Annemarie F. Harrington, Kelly M. Ryabchenko, Karen Castillo, Diane Freund, Rachel Heyman, Richard E. TI PTSD and conflict behavior between veterans and their intimate partners SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Couples; Trauma ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM-WAR VETERANS; MARITAL INTERACTION; COMBAT VETERANS; LIFE EVENTS; COUPLES; FAMILY; ABUSE; ADJUSTMENT; DEPRESSION AB This study examined the influence of trauma history and PTSD symptoms on the behavior of veterans and their intimate partners (287 couples; N = 574) observed during conflict discussions and coded using the Rapid Marital Interaction Coding System (Heyman, 2004). Dyadic structural equation modeling analyses showed that PTSD was associated with more frequent displays of hostility and psychological abuse and fewer expressions of acceptance and humor in both veterans and their partners. Findings provide new insight into the social and emotional deficits associated with PTSD and emphasize the importance of addressing the trauma histories and PTSD of both partners when treating veteran couples with relationship disturbance. Published by Elsevier Ltd. C1 [Miller, Mark W.; Wolf, Erika J.; Reardon, Annemarie F.; Harrington, Kelly M.; Ryabchenko, Karen] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Miller, Mark W.; Wolf, Erika J.; Reardon, Annemarie F.; Harrington, Kelly M.; Ryabchenko, Karen] Boston Univ, Sch Med, Boston, MA 02215 USA. [Castillo, Diane; Freund, Rachel] New Mexico VA Healthcare Syst, Boston, MA USA. [Heyman, Richard E.] NYU, New York, NY 10003 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU NIMH NIH HHS [R01 MH079806] NR 74 TC 10 Z9 10 U1 7 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAR PY 2013 VL 27 IS 2 BP 240 EP 251 DI 10.1016/j.janxdis.2013.02.005 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 136UA UT WOS:000318387700011 PM 23523947 ER PT J AU Deacon, BJ Lickel, JJ Farrell, NR Kemp, JJ Hipol, LJ AF Deacon, Brett J. Lickel, James J. Farrell, Nicholas R. Kemp, Joshua J. Hipol, Leilani J. TI Therapist perceptions and delivery of interoceptive exposure for panic disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Interoceptive exposure; Panic disorder; Diaphragmatic breathing; Treatment ID COGNITIVE-BEHAVIORAL TREATMENT; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; ANXIETY; COMBINATION; AGORAPHOBIA; IMIPRAMINE; EFFICACY AB Interoceptive exposure (IE) is widely regarded as an essential procedure in the cognitive-behavioral treatment of panic disorder (PD). However, treatment manuals differ substantially in their prescribed delivery of IE, and little research exists to inform the optimal manner of its implementation. The present study examined therapists' perceptions and delivery of IE for PD. Results revealed substantial variability in how clinicians provide IE. In contrast to the prolonged and intense manner in which exposure techniques are traditionally applied, many therapists reported delivering a low dose of IE accompanied by controlled breathing strategies. Concerns about the potential adverse effects of IE were common despite the fact that participants reported the actual occurrence of negative outcomes of IE in their own practice to be extremely infrequent. It is possible that some therapists deliver IE in a cautious manner in an attempt to minimize the perceived risks associated with this treatment. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Deacon, Brett J.; Farrell, Nicholas R.; Kemp, Joshua J.; Hipol, Leilani J.] Univ Wyoming, Dept 3415, Dept Psychol, Laramie, WY 82071 USA. [Lickel, James J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Deacon, BJ (reprint author), Univ Wyoming, Dept 3415, Dept Psychol, 1000 East Univ Ave, Laramie, WY 82071 USA. EM bdeacon@uwyo.edu NR 41 TC 20 Z9 20 U1 2 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAR PY 2013 VL 27 IS 2 BP 259 EP 264 DI 10.1016/j.janxdis.2013.02.004 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 136UA UT WOS:000318387700013 PM 23549110 ER PT J AU Tsao, CW O'Donnell, CJ AF Tsao, Connie W. O'Donnell, Christopher J. TI Lipid profiles and coronary artery plaque by CT angiography: Promise for translation of biology to imaging SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Editorial Material ID MULTISLICE COMPUTED-TOMOGRAPHY; ACUTE CHEST-PAIN; CARDIOVASCULAR-DISEASE; MAGNETIC-RESONANCE; PROGNOSTIC VALUE; RISK; CALCIUM; SUBFRACTIONATION; APOLIPOPROTEINS; CHOLESTEROL C1 [Tsao, Connie W.] Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA 01702 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Tsao, CW (reprint author), Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. FU Intramural NIH HHS [ZIA HL006002-06, Z99 HL999999, ZIA HL006002-05] NR 28 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAR-APR PY 2013 VL 7 IS 2 BP 91 EP 93 DI 10.1016/j.jcct.2013.02.001 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 137WV UT WOS:000318469800004 PM 23622504 ER PT J AU Mahadevan, TS Milosevic, M Kojic, M Hussain, F Kojic, N Serda, R Ferrari, M Ziemys, A AF Mahadevan, T. S. Milosevic, M. Kojic, M. Hussain, F. Kojic, N. Serda, R. Ferrari, M. Ziemys, A. TI Diffusion transport of nanoparticles at nanochannel boundaries SO JOURNAL OF NANOPARTICLE RESEARCH LA English DT Article DE Nanoparticle; Nanochannel; Diffusion; Transport; Barrier ID MOLECULAR-DYNAMICS; MESOPOROUS SILICA; NONEQUILIBRIUM; ALGORITHMS; INTERFACE; MODEL AB The manipulation of matter at the nanoscale has unleashed a great potential for engineering biomedical drug carriers, but the transport of nanoparticles (NPs) under nanoscale confinement is still poorly understood. Using colloidal physics to describe NP interactions, we have computationally studied the passive transport of NPs using experimentally relevant conditions from bulk into a nanochannel of 60-90 nm height. NP size, channel height, and the Debye length are comparable so that changes in nanoscale dimensions may induce substantial changes in NP transport kinetics. We show that subtle changes in nanochannel dimensions may alter the energy barrier by about six orders of magnitude resulting in different NP penetration depths and diffusion mechanisms: ballistic, first-order and quasi zero-order transport regimes. The analysis of NP diffusion by continuum methods reveals that apparent diffusivity is reduced by decreasing channel size. The continuum finite element (FE) numerical method reproduced the colloidal model results only when surface interactions were accounted for. These results give a new insight into NP passive transport at the boundaries of nanoconfined domains, and have implications on the design of nanoscale fluidics and NP systems for biomedical and engineering applications. C1 [Mahadevan, T. S.; Kojic, M.; Hussain, F.; Serda, R.; Ferrari, M.; Ziemys, A.] Methodist Hosp, Res Inst, Dept Nanomed, Houston, TX 77030 USA. [Milosevic, M.; Kojic, M.] Univ Metropolitan Belgrade, Bioengn Res & Dev Ctr, Kragujevac 3400, Serbia. [Hussain, F.] Univ Houston, Houston, TX 77204 USA. [Kojic, N.] Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Sch Med, Boston, MA 02114 USA. RP Ziemys, A (reprint author), Methodist Hosp, Res Inst, Dept Nanomed, 6535 Fannin, Houston, TX 77030 USA. EM aziemys@tmhs.org FU Methodist Research Institute; Serbian Ministry of Education and Science [OI 174028]; Ernest Cockrell Jr. Distinguished Endowed Chair; US Department of Defense [W81XWH-09-1-0212]; National Institute of Health [U54CA143837, U54CA151668] FX The authors acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin for providing HPC resources that have contributed to the research results reported within this paper. This project has been partially supported with the Methodist Research Institute, and also by the Grant OI 174028 of the Serbian Ministry of Education and Science. Authors also acknowledge partial supports from the following funding sources: the Ernest Cockrell Jr. Distinguished Endowed Chair (M.F.), US Department of Defense (W81XWH-09-1-0212) (M.F.), National Institute of Health (U54CA143837, U54CA151668) (M.F.). NR 32 TC 3 Z9 3 U1 1 U2 37 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1388-0764 J9 J NANOPART RES JI J. Nanopart. Res. PD MAR PY 2013 VL 15 IS 3 AR 1477 DI 10.1007/s11051-013-1477-9 PG 10 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 138ZP UT WOS:000318551300023 ER PT J AU Nambudiri, VE AF Nambudiri, Vinod E. TI Through the looking-glass SO INDIAN JOURNAL OF DERMATOLOGY VENEREOLOGY & LEPROLOGY LA English DT Editorial Material ID DERMATOLOGY C1 [Nambudiri, Vinod E.] Harvard Univ, Sch Med, Dept Med, Harvard Combined Dermatol Residency Program, Boston, MA USA. [Nambudiri, Vinod E.] Brigham & Womens Hosp, Longwood Med Area, Boston, MA 02115 USA. RP Nambudiri, VE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bartlett Hall 6th Floor, Boston, MA 02114 USA. EM vnambudiri@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0378-6323 J9 INDIAN J DERMATOL VE JI Indian J. Dermatol. Venereol. Leprol. PD MAR-APR PY 2013 VL 79 IS 2 BP 148 EP 150 DI 10.4103/0378-6323.107639 PG 3 WC Dermatology SC Dermatology GA 116TT UT WOS:000316906600002 PM 23442452 ER PT J AU Simonsen, CZ Andersen, G Gonzalez, RG Yoo, AJ AF Simonsen, Claus Z. Andersen, Grethe Gonzalez, R. Gilberto Yoo, Albert J. TI Selection of patients for intra-arterial therapy SO LANCET NEUROLOGY LA English DT Letter ID ISCHEMIC-STROKE; ARTERY C1 [Simonsen, Claus Z.; Andersen, Grethe] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus, Denmark. [Gonzalez, R. Gilberto; Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Diagnost & Intervent Neuroradiol, Boston, MA 02114 USA. RP Simonsen, CZ (reprint author), Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus, Denmark. EM ajyoo@partners.org NR 7 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAR PY 2013 VL 12 IS 3 BP 225 EP 225 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 138SW UT WOS:000318531300007 PM 23415562 ER PT J AU Pardo-Saganta, A Law, BM Gonzalez-Celeiro, M Vinarsky, V Rajagopal, J AF Pardo-Saganta, Ana Law, Brandon M. Gonzalez-Celeiro, Meryem Vinarsky, Vladimir Rajagopal, Jayaraj TI Ciliated Cells of Pseudostratified Airway Epithelium Do Not Become Mucous Cells after Ovalbumin Challenge SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE mucous cell metaplasia; pseudostratified airway epithelium; ovalbumin; ciliated cell; goblet or mucous cell ID PANCREATIC EXOCRINE CELLS; BASAL STEM-CELLS; GOBLET-CELL; RESPIRATORY EPITHELIUM; MUCUS HYPERSECRETION; ALLERGIC-ASTHMA; MOUSE TRACHEA; CLARA CELLS; IN-VIVO; METAPLASIA AB Mucous cell metaplasia is a hallmark of airway diseases, such as asthma and chronic obstructive pulmonary disease. The majority of human airway epithelium is pseudostratified, but the cell of origin of mucous cells has not been definitively established in this type of airway epithelium. There is evidence that ciliated, club cell (Clara), and basal cells can all give rise to mucus-producing cells in different contexts. Because pseudostratified airway epithelium contains distinct progenitor cells from simple columnar airway epithelium, the lineage relationships of progenitor cells to mucous cells may be different in these two epithelial types. We therefore performed lineage tracing of the ciliated cells of the murine basal cell-containing airway epithelium in conjunction with the ovalbumin (OVA)-induced murine model of allergic lung disease. We genetically labeled ciliated cells with enhanced Yellow Fluorescent Protein (eYFP) before the allergen challenge, and followed the fate of these cells to determine whether they gave rise to newly formed mucous cells. Although ciliated cells increased in number after the OVA challenge, the newly formed mucous cells were not labeled with the eYFP lineage tag. Even small numbers of labeled mucous cells could not be detected, implying that ciliated cells make virtually no contribution to the new goblet cell pool. This demonstrates that, after OVA challenge, new mucous cells do not originate from ciliated cells in a pseudostratified basal cell-containing airway epithelium. C1 [Pardo-Saganta, Ana; Law, Brandon M.; Gonzalez-Celeiro, Meryem; Vinarsky, Vladimir; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Pediat, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Rajagopal, Jayaraj] Harvard Stem Cell Inst, Cambridge, MA USA. RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Simches 4-240,185 Cambridge St, Boston, MA 02114 USA. EM jrajagopal@partners.org FU National Institutes of Health-National Heart, Lung, and Blood Institute Early Career Research New Faculty [5P30HL101287-02]; Harvard Stem Cell Institute Junior Investigator Grant FX This work was supported by National Institutes of Health-National Heart, Lung, and Blood Institute Early Career Research New Faculty (P30) award 5P30HL101287-02 and Harvard Stem Cell Institute Junior Investigator Grant (J.R.). NR 40 TC 12 Z9 13 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 2013 VL 48 IS 3 BP 364 EP 373 DI 10.1165/rcmb.2012-0146OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 135EE UT WOS:000318269400013 PM 23239495 ER PT J AU Farnsworth, SL Qiu, ZF Mishra, A Hornsby, PJ AF Farnsworth, Steven L. Qiu, Zhifang Mishra, Anuja Hornsby, Peter J. TI Directed neural differentiation of induced pluripotent stem cells from non-human primates SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE induced pluripotent stem cells; non-human primates; differentiation; cell therapy ID REGENERATIVE MEDICINE; FATE; INDUCTION; BIOLOGY; GENERATION; CONVERSION; INHIBITOR; DISCOVERY; NEURONS; SIGNALS AB Induced pluripotent stem cells (iPS cells) are important for the future development of regenerative medicine involving autologous cell therapy. Before autologous cell therapy can be applied to human patients, suitable animal models must be developed, and in this context non-human primate models are critical. We previously characterized several lines of marmoset iPS cells derived from newborn skin fibroblasts. In the present studies, we explored methods for the directed differentiation of marmoset iPS cells in the neuroectodermal lineage. In this process we used an iterative process in which combinations of small molecules and protein factors were tested for their effects on mRNA levels of genes that are markers for the neuroectodermal lineage. This iterative process identified combinations of chemicals/factors that substantially improved the degree of marker gene expression over the initially tested combinations. This approach should be generally valuable in the directed differentiation of pluripotent cells for experimental cell therapy. C1 [Farnsworth, Steven L.; Qiu, Zhifang; Mishra, Anuja; Hornsby, Peter J.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Farnsworth, Steven L.; Qiu, Zhifang; Mishra, Anuja; Hornsby, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Farnsworth, Steven L.; Qiu, Zhifang; Mishra, Anuja; Hornsby, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. RP Hornsby, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM hornsby@uthscsa.edu RI Qiu, Zhifang/P-8313-2014; OI Qiu, Zhifang/0000-0001-9196-032X FU Department of Veterans Affairs [I01BX001454]; Ted Nash Long Life Foundation; Owens Medical Foundation; COSTAR [T32DE014318]; [F30DE022494] FX This work was supported by grant I01BX001454 from the Department of Veterans Affairs to PJH, and also by grants from the Ted Nash Long Life Foundation and the Owens Medical Foundation. SLF was supported by an individual fellowship (F30DE022494) and by the COSTAR training grant T32DE014318. NR 30 TC 5 Z9 5 U1 0 U2 9 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD MAR PY 2013 VL 238 IS 3 BP 276 EP 284 DI 10.1177/1535370213482442 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 134DA UT WOS:000318188900004 PM 23598973 ER PT J AU Hadlock, TA Kim, SW Weinberg, JS Knox, CJ Hohman, MH Heaton, JT AF Hadlock, Tessa A. Kim, Sang W. Weinberg, Julie S. Knox, Christopher J. Hohman, Marc H. Heaton, James T. TI Quantitative Analysis of Muscle Histologic Method in Rodent Facial Nerve Injury SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID MECHANICAL STIMULATION; INTERSTITIAL FIBROSIS; FUNCTIONAL RECOVERY; CONNECTIVE-TISSUE; WHISKER MOVEMENTS; SKELETAL-MUSCLE; IMAGE-ANALYSIS; MOTOR UNITS; QUANTIFICATION; REGENERATION AB Objective: To describe denervation features of facial musculature following facial nerve injury in a rodent model. Methods: Six Wistar-Hannover rats underwent unilateral transection and immediate repair of the facial nerve. After 8 weeks, muscular bundles consisting of dilator naris and levator labii superioris from both sides were analyzed for mean muscle cell diameter and the percentage of muscle cell cross-sectional area using image processing software. The atrophic features of facial muscles were quantified and compared with the contralateral, healthy side of the face. Results: Weekly postoperative whisking assessment demonstrated the anticipated course of recovery. We observed significant differences between the normal side and the manipulated side, respectively, in the percent-age of muscle specimen cross-sectional area attributable to muscle cell profiles (57% vs 29%; P=.006) and total fiber counts (1346 vs 794; P=.02). The mean cross-sectional area of individual muscle fibers was higher on the normal side (1129 vs 928 mu m(2); P=.39); however, this difference was statistically nonsignificant. Conclusion: The objective, quantitative measures of muscle microstructure used in this report provide a valuable point of comparison for whisking function and electrophysiologic measures and can be used in future studies to assess muscle atrophic features associated with facial nerve injury and repair techniques. JAMA Facial Plast Surg. 2013;15(2):141-146. Published online January 17, 2013. doi:10.1001/jamafacial.2013.430 C1 [Hadlock, Tessa A.; Kim, Sang W.; Weinberg, Julie S.; Knox, Christopher J.; Hohman, Marc H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Tessa_Hadlock@meei.harvard.edu FU Leslie Bernstein resident research grant from the American Academy of Facial Plastic and Reconstructive Surgery FX This study was funded by the Leslie Bernstein resident research grant 2011 from the American Academy of Facial Plastic and Reconstructive Surgery. NR 36 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6076 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD MAR-APR PY 2013 VL 15 IS 2 BP 141 EP 146 DI 10.1001/jamafacial.2013.430 PG 6 WC Surgery SC Surgery GA 133OI UT WOS:000318147600012 PM 23329158 ER PT J AU Gorlach, I Pham-Kanter, G AF Gorlach, Igor Pham-Kanter, Genevieve TI Brightening Up: The Effect of the Physician Payment Sunshine Act on Existing Regulation of Pharmaceutical Marketing SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article AB With the passage of the Physician Payment Sunshine Act as part of the federal health care reform law, pharmaceutical manufacturers are now required to disclose a wide range of payments made by manufacturers to physicians. We review current state regulation of pharmaceutical marketing and consider how the federal sunshine provision will affect existing marketing regulation. We analyze the legal and practical implications of the Physician Payment Sunshine Act. C1 [Pham-Kanter, Genevieve] Harvard Univ, Cambridge, MA 02138 USA. [Pham-Kanter, Genevieve] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pham-Kanter, Genevieve] Univ Colorado, Sch Publ Hlth, Denver, CO 80202 USA. [Pham-Kanter, Genevieve] Univ Colorado, Dept Econ, Denver, CO 80202 USA. OI Pham-Kanter, Genevieve/0000-0002-3044-7829 NR 2 TC 12 Z9 12 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2013 VL 41 IS 1 SI SI BP 315 EP 322 DI 10.1111/jlme.12022 PG 8 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 130IY UT WOS:000317909200022 PM 23581674 ER PT J AU Liao, JM Singh, H AF Liao, Joshua M. Singh, Hardeep TI Reviving the Autopsy as a Diagnostic Error-Reduction Tool SO LABMEDICINE LA English DT Article DE diagnostic errors; autopsy; medical error; patient safety; pathology AB Errors are estimated to occur in 10% to 15% of all diagnoses and can lead to significant harm and costs. An autopsy can reveal clinically significant diagnoses missed before death. Multiple studies have reported poor concordance between clinical and autopsy diagnoses; thus, autopsy remains a powerful tool for the study of diagnostic errors. Although there are benefits to autopsy in the era of advanced diagnostic technology, many barriers exist. In this article, we discuss the role of autopsy in reducing diagnostic errors and make several recommendations of how to invigorate efforts to support autopsy as a potential diagnostic error reduction tool. A resurgence of autopsy as a learning tool will require not only focus on the actions of requesting physicians or pathologists, but also a systems-based approach, including nonphysician personnel, health information technology, reimbursement initiatives, and incentives to promote the use of autopsy. C1 [Liao, Joshua M.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Singh, Hardeep] Baylor Coll Med, Houston VA Hlth Serv Res & Dev HSR&D, Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Singh, H (reprint author), Baylor Coll Med, Houston VA Hlth Serv Res & Dev HSR&D, Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU Houston VA Health Services Research and Development Center of Excellence at the Michael E. DeBakey VA Medical Center, Houston, TX [HFP90-020] FX The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. This paper is supported with resources and the use of facilities at the Houston VA Health Services Research and Development Center of Excellence (HFP90-020) at the Michael E. DeBakey VA Medical Center, Houston, TX. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD SPR PY 2013 VL 44 IS 2 BP 186 EP 190 DI 10.1309/LMI9N2TS8YTQLBDI PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 132HK UT WOS:000318058300017 ER PT J AU Ngwenya, LB Chiocca, A AF Ngwenya, Laura B. Chiocca, Antonio TI Do Meningioma Patients Benefit from Antiepileptic Drug Treatment? SO WORLD NEUROSURGERY LA English DT Editorial Material ID SEIZURES; RESECTION; SURGERY C1 [Ngwenya, Laura B.] James Canc Hosp, Dept Neurol Surg, Columbus, OH USA. [Ngwenya, Laura B.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Chiocca, Antonio] Harvard Univ, Sch Med, Brigham & Womens Faulkner Hosp, Inst Neurosci,Dept Neurosurg, Boston, MA USA. [Chiocca, Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM EA.Chiocca@osumc.edu NR 6 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 J9 WORLD NEUROSURG JI World Neurosurg. PD MAR-APR PY 2013 VL 79 IS 3-4 BP 433 EP 434 DI 10.1016/j.wneu.2012.05.013 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 135CC UT WOS:000318262600011 PM 22634463 ER PT J AU Carrion, IV Nedjat-Haiem, FR AF Carrion, Iraida V. Nedjat-Haiem, Frances R. TI Caregiving for Older Latinos at End of Life: Perspectives From Paid and Family (Unpaid) Caregivers SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE Latinos; end of life; family (unpaid) caregiving; paid caregiving; hospice; settings ID OF-LIFE; QUALITATIVE RESEARCH; INFORMAL CAREGIVERS; HEALTH-CARE; CANCER CAREGIVERS; DECISION-MAKING; UNMET NEEDS; ISSUES; DETERMINANTS; CONSTRUCTION AB This study examined the various settings in which caregiving occurred for terminally ill older Latinos. Qualitative data were collected in Central Florida through in-depth, semi-structured, open-ended interviews. 20 Latinos caring for terminally ill Latinos participated in the study. N = 9 Latino family (unpaid) caregivers provided care in the terminally ill person's home, while N = 4 provided care to a family member in the caregiver's home. N = 4 paid caregivers provided care to terminally ill Latinos who reside in the caregiver's private home and N = 3 in an assisted-living facility. The themes indicate that family (unpaid) caregivers experienced changes in their financial status; they both encountered English language barriers. Geographical distance made caregiving more challenging. Paid caregivers adapted to cultural expectations and their higher income enabled them to hire assistance. C1 [Carrion, Iraida V.] Univ S Florida, Sch Social Work, Tampa, FL 33612 USA. [Nedjat-Haiem, Frances R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Carrion, IV (reprint author), Univ S Florida, Coll Behav & Community Sci, Sch Social Work, 13301 Bruce B Downs Blvd,MHC 1438, Tampa, FL 33612 USA. EM icarrion@usf.edu OI Carrion, Iraida/0000-0003-4076-6644 NR 57 TC 6 Z9 6 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD MAR PY 2013 VL 30 IS 2 BP 183 EP 191 DI 10.1177/1049909112448227 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 127CQ UT WOS:000317673400013 PM 22637704 ER PT J AU van Leyen, K AF van Leyen, Klaus TI Lipoxygenase: An Emerging Target for Stroke Therapy SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Ischemic stroke; neuroprotection; oxidative stress; eicosanoid; lipoxygenase; arachidonic acid cascade ID FOCAL CEREBRAL-ISCHEMIA; HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; CYTOSOLIC PHOSPHOLIPASE A(2); FREE-RADICAL SCAVENGER; E ALPHA-TOCOTRIENOL; CELL-DEATH; OXIDATIVE STRESS; ORGANELLE DEGRADATION; CORTICAL-NEURONS; LIPID MEDIATORS AB Neuroprotection as approach to stroke therapy has recently seen a revival of sorts, fueled in part by the continuing necessity to improve acute stroke care, and in part by the identification of novel drug targets. 12/15-Lipoxygenase (12/15-LOX), one of the key enzymes of the arachidonic acid cascade, contributes to both neuronal cell death and vascular injury. Inhibition of 12/15-LOX may thus provide multifactorial protection against ischemic injury. Targeting 12/15-LOX and related eicosanoid pathways is the subject of this brief review. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, 149 13th St,R 2401, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu FU National Institutes of Health [R01NS049430, R01NS069939] FX Support from the National Institutes of Health (R01NS049430 and R01NS069939) is gratefully acknowledged. A patent on the use of LOXBlock inhibitors to treat stroke has been applied for (U.S. Patent Application No.: 12/671,567). NR 124 TC 13 Z9 13 U1 2 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD MAR PY 2013 VL 12 IS 2 BP 191 EP 199 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 126YQ UT WOS:000317659600005 PM 23394536 ER PT J AU Blumenthal, KJ Saulsgiver, KA Norton, L Troxel, AB Anarella, JP Gesten, FC Chernew, ME Volpp, KG AF Blumenthal, Karen J. Saulsgiver, Kathryn A. Norton, Laurie Troxel, Andrea B. Anarella, Joseph P. Gesten, Foster C. Chernew, Michael E. Volpp, Kevin G. TI Medicaid Incentive Programs To Encourage Healthy Behavior Show Mixed Results To Date And Should Be Studied And Improved SO HEALTH AFFAIRS LA English DT Article ID FINANCIAL INCENTIVES; CONTINGENCY MANAGEMENT; SMOKING-CESSATION; PAY AB In September 2011 the Centers for Medicare and Medicaid Services awarded $85 million in grants to ten states to test financial incentive programs to encourage healthy behavior among Medicaid enrollees with chronic diseases. There is little published evidence about the effectiveness of such incentives within the Medicaid program. We evaluated the available research from three earlier Medicaid incentive programs and found mixed results. On the one hand, in Florida only about half of the $41.3 million in available credits was "claimed" by enrollees between 2006 and 2011. On the other, Idaho's incentive program was credited with improving the proportion of children who were up-to-date on well-child visits. Our findings suggest that Medicaid incentive programs should be designed so that enrollees can understand them and so that the incentives are attractive enough to motivate participation. Medicaid incentive programs also should be subject to rigorous evaluation to more clearly establish their effectiveness. C1 [Blumenthal, Karen J.] Massachusetts Gen Hosp, Internal Med Primary Care Program, Boston, MA 02114 USA. [Saulsgiver, Kathryn A.; Norton, Laurie] Univ Penn, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Troxel, Andrea B.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Troxel, Andrea B.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Anarella, Joseph P.; Gesten, Foster C.] New York State Dept Hlth, Off Qual & Patient Safety, Albany, NY 12237 USA. [Chernew, Michael E.] Harvard Univ, Sch Med, Boston, MA USA. [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Blumenthal, KJ (reprint author), Massachusetts Gen Hosp, Internal Med Primary Care Program, Boston, MA 02114 USA. EM kjblumenthal@gmail.com OI Troxel, Andrea/0000-0002-1393-3075 FU Center for Medicare; Center for Medicaid Services' [1B1CMS330902-01-01]; Discovery (South Africa); McKinsey; Humana; Weight Watchers; Horizon Blue Cross Blue Shield; National Institutes of Health FX The authors acknowledge funding from the Centers for Medicare and Medicaid Services' Medicaid Incentives for the Prevention of Chronic Disease grant program (No. 1B1CMS330902-01-01). Kevin Volpp reports receipt of research funding from Discovery (South Africa), McKinsey, Humana, Weight Watchers, and Horizon Blue Cross Blue Shield; receipt of research funding to his institution from the National Institutes of Health; and provision of consulting services to VAL Healthand CVS-Caremark. NR 46 TC 17 Z9 17 U1 1 U2 12 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR PY 2013 VL 32 IS 3 BP 497 EP 507 DI 10.1377/hlthaff.2012.0431 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 111YK UT WOS:000316557900008 PM 23459728 ER PT J AU Shi, FX Edge, ASB AF Shi, Fuxin Edge, Albert S. B. TI Prospects for replacement of auditory neurons by stem cells SO HEARING RESEARCH LA English DT Review ID SPIRAL GANGLION NEURONS; INDUCED HEARING-LOSS; SPINAL-CORD-INJURY; GUINEA-PIG COCHLEA; MOUSE INNER-EAR; HAIR-CELLS; SENSORY NEURONS; NERVE-FIBERS; IN-VITRO; BRAIN-STEM AB Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regenerative approaches. In this review we critically present the current experimental findings on auditory neuron replacement. We discuss the latest advances with a focus on (a) exogenous stem cell transplantation into the cochlea for neural replacement, (b) expression of local guidance signals in the cochlea after loss of auditory neurons, (c) the possibility of neural replacement from an endogenous cell source, and (d) functional changes from cell engraftment. (C) 2013 Elsevier B.V. All rights reserved. C1 [Shi, Fuxin; Edge, Albert S. B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Shi, Fuxin; Edge, Albert S. B.] Harvard Univ, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Edge, Albert S. B.] Div Hlth Sci & Technol Harvard & MIT, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. RP Edge, ASB (reprint author), Harvard Univ, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM albert_edge@meei.harvard.edu FU National Institute on Deafness and other Communicative Disorders [RO1 DC007174, P30 DC05209] FX This work was supported by grants RO1 DC007174 and P30 DC05209 from the National Institute on Deafness and other Communicative Disorders. NR 112 TC 14 Z9 16 U1 1 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2013 VL 297 SI SI BP 106 EP 112 DI 10.1016/j.heares.2013.01.017 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 127NW UT WOS:000317706700012 PM 23370457 ER PT J AU Jones, C Missanelli, M Dure, L Funkhouser, E Kaffka, J Kilgore, M Saag, K Yu, F Safford, MM AF Jones, Charlotte Missanelli, Megan Dure, Leon Funkhouser, Ellen Kaffka, Jaimee Kilgore, Meredith Saag, Kenneth Yu, Feliciano Safford, Monika M. TI Anticonvulsant Medication Errors in Children With Epilepsy During the Home-to-Hospital Transition SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE patient safety; medication errors; epilepsy; transitions ID ADVERSE DRUG EVENTS; CHRONIC HEALTH CONDITIONS; SEVERE ACUTE ILLNESS; PEDIATRIC INPATIENTS; CARE TRANSITIONS; PATIENT SAFETY AB Children with epilepsy are at risk of having their anticonvulsant regimens disrupted during the home-to-hospital transition. We sought to estimate the frequency of anticonvulsant medication errors during transition into the hospital in children with epilepsy hospitalized for reasons other than seizures, and to examine factors associated with the occurrence of such errors. We examined the medical records to identify errors related to anticonvulsant administration during the transition into the hospital and we examined potential risk factors for error occurrence. Errors were classified as relating to dosing quantity or missing a dose. Among 120 children, 29 (24%) experienced an anticonvulsant medication error. In a multivariable model, the risk factors of changes in responsibility for anticonvulsant administration and frequency of anticonvulsant administration were strongly associated with increased odds of errors. Anticonvulsant medication errors during the home-to-hospital transition may be unacceptably common in children with epilepsy hospitalized for reasons other than seizures. C1 [Jones, Charlotte] Ohio State Univ, Dept Pediat, Div Pediat Neurol, Nationwide Childrens Hosp, Columbus, OH 43205 USA. [Missanelli, Megan] Univ S Alabama, Coll Med, Mobile, AL USA. [Dure, Leon] Univ Alabama Birmingham, Sch Med, Dept Pediat, Div Pediat Neurol, Birmingham, AL USA. [Funkhouser, Ellen] Univ Alabama Birmingham, Sch Med, Dept Med, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. [Funkhouser, Ellen] Birmingham VA Med Ctr, VA Res Enhancement Award Program, Birmingham, AL USA. [Kaffka, Jaimee] Univ Alabama Birmingham, Med Sch Birmingham, Div Continuing Med Educ, Birmingham, AL USA. [Kilgore, Meredith] Univ Alabama Birmingham, Sch Publ Hlth, Sch Med, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL 35294 USA. [Saag, Kenneth] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol,Sch Med, Ctr Educ & Res Therapeut CERTS Musculoskeletal Di, Dept Med,Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. [Yu, Feliciano] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Safford, Monika M.] Univ Alabama Birmingham, Sch Med, Ctr Outcomes & Effectiveness Res & Educ, Dept Med,Div Prevent Med,Div Continuing Med Educ, Birmingham, AL USA. RP Jones, C (reprint author), Ohio State Univ, Dept Pediat, Div Pediat Neurol, Nationwide Childrens Hosp, 700 Childrens Dr ED 520, Columbus, OH 43205 USA. EM Charlotte.Jones@Nationwidechildrens.org FU Agency for Healthcare Research and Quality [5T32HS013852-08]; Center for Outcomes and Effectiveness Research at the University of Alabama, Birmingham, Alabama FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr Jones was supported by a grant (No. 5T32HS013852-08) from the Agency for Healthcare Research and Quality and funding was provided by the Center for Outcomes and Effectiveness Research at the University of Alabama, Birmingham, Alabama. NR 25 TC 7 Z9 7 U1 1 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAR PY 2013 VL 28 IS 3 BP 314 EP 320 DI 10.1177/0883073812446632 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 127ER UT WOS:000317680100006 PM 22752478 ER PT J AU Lund, BC Charlton, ME Steinman, MA Kaboli, PJ AF Lund, Brian C. Charlton, Mary E. Steinman, Michael A. Kaboli, Peter J. TI Regional Differences in Prescribing Quality Among Elder Veterans and the Impact of Rural Residence SO JOURNAL OF RURAL HEALTH LA English DT Article DE geography; geriatrics; pharmacy; quality; rural ID INAPPROPRIATE MEDICATION USE; ADVERSE DRUG-REACTIONS; OLDER-ADULTS; BEERS CRITERIA; EXPLICIT CRITERIA; UNITED-STATES; RISK; CARE; POPULATION; PRESCRIPTION AB Purpose: Medication safety is a critical concern for older adults. Regional variation in potentially inappropriate prescribing practices may reflect important differences in health care quality. Therefore, the objectives of this study were to characterize prescribing quality variation among older adults across geographic region, and to compare prescribing quality across rural versus urban residence. Methods: Cross-sectional study of 1,549,824 older adult veterans with regular Veterans Affairs (VA) primary care and medication use during fiscal year 2007. Prescribing quality was measured by 4 indicators of potentially inappropriate prescribing: Zhan criteria drugs to avoid, Fick criteria drugs to avoid, therapeutic duplication, and drug-drug interactions. Frequency differences across region and rural-urban residence were compared using adjusted odds-ratios. Findings: Significant regional variation was observed for all indicators. Zhan criteria frequencies ranged from 13.2% in the Northeast to 21.2% in the South. Nationally, rural veterans had a significantly increased risk for inappropriate prescribing according to all quality indicators. However, regional analyses revealed this effect was limited to the South and Northeast, whereas rural residence was neutral in the Midwest and protective in the West. Conclusions: Significant regional variation in prescribing quality was observed among older adult veterans, mirroring recent findings among Medicare beneficiaries. The association between rurality and prescribing quality is heterogeneous, and relying solely on national estimates may yield misleading conclusions. Although we documented important variations in prescribing quality, the underlying factors driving these trends remain unknown, and they are a vital area for future research affecting older adults in both VA and non-VA health systems. C1 [Lund, Brian C.; Charlton, Mary E.; Kaboli, Peter J.] VA Iowa City Hlth Care Syst, Vet Rural Hlth Resource Ctr Cent Reg, Iowa City, IA 52246 USA. [Lund, Brian C.; Kaboli, Peter J.] VA Iowa City Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA 52246 USA. [Lund, Brian C.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Steinman, Michael A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Steinman, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kaboli, Peter J.] Univ Iowa, Dept Internal Med, Div Gen Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. RP Lund, BC (reprint author), VA Iowa City Hlth Care Syst, Mailstop 152,601 Hwy 6 West, Iowa City, IA 52246 USA. EM Brian.Lund@va.gov FU Veterans Rural Health Resource Center-Central Region [IMV 04-066-1]; Center for Comprehensive Access & Delivery Research and Evaluation [REA 09-220]; Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics [5 U18 HSO16094]; Career Development Award from the Health Services Research and Development Service, Department of Veterans Affairs [CDA 10-017]; National Institute on Aging; American Federation for Aging Research [K23-AG030999] FX This research was supported by the Veterans Rural Health Resource Center-Central Region (IMV 04-066-1) and the Center for Comprehensive Access & Delivery Research and Evaluation (REA 09-220). This study was also supported in part by an Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics cooperative agreement #5 U18 HSO16094. Dr. Lund was supported by a Career Development Award from the Health Services Research and Development Service, Department of Veterans Affairs (CDA 10-017). Dr. Steinman was supported by an award from the National Institute on Aging and the American Federation for Aging Research (K23-AG030999). NR 47 TC 12 Z9 12 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0890-765X EI 1748-0361 J9 J RURAL HEALTH JI J. Rural Health PD SPR PY 2013 VL 29 IS 2 BP 172 EP 179 DI 10.1111/j.1748-0361.2012.00428.x PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 119CB UT WOS:000317073400006 PM 23551647 ER PT J AU Bolognini, N Convento, S Rossetti, A Merabet, LB AF Bolognini, Nadia Convento, Silvia Rossetti, Angela Merabet, Lotfi B. TI Multisensory processing after a brain damage: Clues on post-injury crossmodal plasticity from neuropsychology SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Multisensory; Perception; Brain damage; Neuropsychology; Plasticity ID SUPERNUMERARY PHANTOM LIMB; OF-BODY EXPERIENCE; DORSAL COCHLEAR NUCLEUS; SPATIAL ATTENTION; PARIETAL CORTEX; NEUROCOGNITIVE MECHANISMS; PERCEPTUAL ENHANCEMENT; VISUOSPATIAL NEGLECT; SELF-CONSCIOUSNESS; AUDIOVISUAL SPEECH AB Current neuropsychological evidence demonstrates that damage to sensory-specific and heteromodal areas of the brain not only disrupts the ability of combining sensory information from multiple sources, but can also cause altered multisensory experiences. On the other hand, there is also evidence of behavioural benefits induced by spared multisensory mechanisms. Thus, crossmodal plasticity can be viewed in both an adaptive and maladaptive context. The emerging view is that different crossmodal plastic changes can result following damage to sensory-specific and heteromodal areas, with post-injury crossmodal plasticity representing an attempt of a multisensory system to reconnect the various senses and by-pass injured areas. Changes can be considered adaptive when there is compensation for the lesion-induced sensory impairment. Conversely, it may prove maladaptive when atypical or even illusory multisensory experiences are generated as a result of re-arranged multisensory networks. This theoretical framework posits new intriguing questions for neuropsychological research and places greater emphasis on the study of multisensory phenomena within the context of damage to large-scale brain networks, rather than just focal damage alone. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Bolognini, Nadia; Convento, Silvia; Rossetti, Angela] Univ Milano Bicocca, Dept Psychol, I-20126 Milan, Italy. [Bolognini, Nadia] IRCCS, Ist Auxol Italian, Neuropsychol Lab, Milan, Italy. [Merabet, Lotfi B.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Lab Visual Neuroplast, Boston, MA 02114 USA. RP Bolognini, N (reprint author), Univ Milano Bicocca, Dept Psychol, Piazza Ateneo Nuovo 1,Ed U6, I-20126 Milan, Italy. EM nadia.bolognini@unimib.it; s.convento@campus.unimib.it; a.rossetti5@campus.unimib.it; lotfi_merabet@meei.harvard.edu RI BOLOGNINI, NADIA/J-5746-2016; ROSSETTI, ANGELA/J-6582-2016 OI BOLOGNINI, NADIA/0000-0002-2921-8658; ROSSETTI, ANGELA/0000-0003-4273-083X FU University of Milano-Bicocca (F.A.R.); NIH/NEI [EY019924] FX This work was supported by grants from the University of Milano-Bicocca (F.A.R. 2011) to N.B. and an NIH/NEI RO1 GRANT EY019924 to L.B.M. NR 116 TC 15 Z9 15 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD MAR PY 2013 VL 37 IS 3 BP 269 EP 278 DI 10.1016/j.neubiorev.2012.12.006 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 125OC UT WOS:000317548100004 PM 23253947 ER PT J AU Lim, CS Baldessarini, RJ Vieta, E Yucel, M Bora, E Sim, K AF Lim, Chin Siang Baldessarini, Ross J. Vieta, Eduard Yucel, Murat Bora, Emre Sim, Kang TI Longitudinal neuroimaging and neuropsychological changes in bipolar disorder patients: Review of the evidence SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Bipolar disorder; Brain imaging; Cognition; Gray matter; Neuroimaging ID GRAY-MATTER VOLUME; ANTERIOR CINGULATE CORTEX; 1ST-EPISODE AFFECTIVE PSYCHOSIS; MAJOR DEPRESSIVE DISORDER; 1ST MANIC EPISODE; I DISORDER; FOLLOW-UP; PREFRONTAL CORTEX; NEUROCOGNITIVE IMPAIRMENT; ORBITOFRONTAL CORTEX AB Longitudinal studies of biological domains in bipolar disorder (BD) are crucial in determining if such baseline changes are progressive. We reviewed reported studies of longitudinal brain structural/functional magnetic resonance imaging (MRI) and neuropsychological changes in BD through November 2012. Longitudinal brain structural MRI studies suggest cortical and subcortical abnormalities within networks subserving emotional regulation. There is evidence of neuroprogressive loss of gray matter volume in prefrontal and anterior cingulate cortex and the subgenual region, with less consistent findings in temporal and subcortical regions. Abnormal amygdala neurodevelopment is noted in adolescent onset BD and possible changes in hippocampus require further evaluation. The fewer reported longitudinal functional MRI studies suggest neurobiological changes in activation patterns involving fronto-limbic circuitry which relate to different illness phase and mood states. Early onset pediatric/adolescent BD may signify a more malignant course of illness in which extensive and executive neurocognitive deficits are found early and may persist, with some potential for improvement during remission and perhaps with treatment. Future studies should include larger samples, combine investigational modalities, incorporate genetic profiles, consider standardization of assessments and collaborative ventures across institutions, selection of more homogeneous subgroups and track neurobiological changes longer to clarify trajectories of changes. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Lim, Chin Siang] Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore. [Lim, Chin Siang; Sim, Kang] Inst Mental Hlth, Dept Gen Psychiat Res, Singapore 539747, Singapore. [Baldessarini, Ross J.] Harvard Univ, Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, Dept Psychiat,Med Sch,McLean Div, Boston, MA USA. [Vieta, Eduard] Univ Clin Hosp Barcelona, Clin Inst Neurosci, Bipolar Disorders Program, IDIBAPS,CIBERSAM, Barcelona, Catalonia, Spain. [Yucel, Murat; Bora, Emre] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Melbourne, Vic 3010, Australia. [Yucel, Murat; Bora, Emre] Melbourne Hlth, Melbourne, Vic, Australia. RP Sim, K (reprint author), Inst Mental Hlth, Dept Gen Psychiat, 10 Buangkok View, Singapore 539747, Singapore. EM kang_sim@imh.com.sg RI Vieta, Eduard/I-6330-2013; bora, emre/D-4123-2009; OI Vieta, Eduard/0000-0002-0548-0053; bora, emre/0000-0002-1598-6832; Yucel, Murat/0000-0002-4705-452X FU NHG [SIG/12004]; SBIC [RP C-009/2006]; Bruce J. Anderson Foundation; McLean Private Donors Bipolar Disorder Research Fund FX This study was supported by NHG (SIG/12004) and SBIC (RP C-009/2006) research grants awarded to KS and, in part by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Bipolar Disorder Research Fund (to RJB). NR 140 TC 60 Z9 62 U1 5 U2 33 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD MAR PY 2013 VL 37 IS 3 BP 418 EP 435 DI 10.1016/j.neubiorev.2013.01.003 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 125OC UT WOS:000317548100015 PM 23318228 ER PT J AU Arango, NA Li, L Dabir, D Nicolau, F Pieretti-Vanmarcke, R Koehler, C McCarrey, JR Lu, NF Donahoe, PK AF Arango, Nelson Alexander Li, Li Dabir, Deepa Nicolau, Fotini Pieretti-Vanmarcke, Rafael Koehler, Carla McCarrey, John R. Lu, Naifang Donahoe, Patricia K. TI Meiosis I Arrest Abnormalities Lead to Severe Oligozoospermia in Meiosis 1 Arresting Protein (M1ap)-Deficient Mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE infertility; meiosis; meiotic arrest; oligozoospermia; spermatogenesis; testis; vertebrates ID MALE GERM-CELLS; MEIOTIC RECOMBINATION; MOUSE SPERMATOCYTES; SPINDLE CHECKPOINT; MALE-FERTILITY; BODY FORMATION; SPERMATOGENESIS; GENE; CHROMOSOMES; EXPRESSION AB Meiosis1 arresting protein ( M1ap) is a novel vertebrate gene expressed exclusively in germ cells of the embryonic ovary and the adult testis. In male mice, M1ap expression, which is present from spermatogonia to secondary spermatocytes, is evolutionarily conserved and has a specific spatial and temporal pattern suggestive of a role during germ cell development. To test its function, mice deficient in M1ap were created. Whereas females had histologically normal ovaries, males exhibited reduced testicular size and a myriad of tubular defects, which led to severe oligozoospermia and infertility. Although some germ cells arrested at the zygotene/ pachytene stages, most cells advanced to metaphase I before arresting and entering apoptosis. Cells that reached metaphase I were unable to properly align their chromosomes at the metaphase plate due to abnormal chromosome synapses and failure to form crossover foci. Depending on the state of tubular degeneration, all germ cells, with the exemption of spermatogonia, disappeared; with further deterioration, tubules displaying only Sertoli cells reminiscent of Sertoli cell-only syndrome in humans were observed. Our results uncovered an essential role for M1ap as a novel germ cell gene not previously implicated in male germ cell development and suggest that mutations in M1AP could account for some cases of nonobstructive oligozoospermia in men. C1 [Arango, Nelson Alexander; Nicolau, Fotini; Pieretti-Vanmarcke, Rafael; Donahoe, Patricia K.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. [Arango, Nelson Alexander; Li, Li; Nicolau, Fotini; Pieretti-Vanmarcke, Rafael; Lu, Naifang; Donahoe, Patricia K.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Li] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Dabir, Deepa] Loyola Marymount Univ, Dept Biol, Los Angeles, CA 90045 USA. [Koehler, Carla] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA. [McCarrey, John R.] Univ Texas San Antonio, Dept Cell & Mol Biol, San Antonio, TX USA. [Lu, Naifang] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Arango, NA (reprint author), Boston Univ, Dept Dermatol, 607 Albany St,Room 409, Boston, MA 02118 USA. EM aarango@bu.edu FU SURDNA/GAR Fellowship Fund from the Department of Surgery, Massachusetts General Hospital; NIH National Cancer Institute [PA-05-015, CA17393] FX This work was supported in part by the SURDNA/GAR Fellowship Fund from the Department of Surgery, Massachusetts General Hospital, and NIH National Cancer Institute, supplement grant PA-05-015 to N.A.A. and research grant CA17393 to P.K.D. NR 47 TC 1 Z9 2 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 2013 VL 88 IS 3 AR 76 DI 10.1095/biolreprod.111.098673 PG 11 WC Reproductive Biology SC Reproductive Biology GA 124NJ UT WOS:000317471100017 PM 23269666 ER PT J AU Garber, JE AF Garber, J. E. TI OBESITY AND ENDOCRINE THERAPY: HOST FACTORS AND BREAST CANCER OUTCOME SO BREAST LA English DT Meeting Abstract ID BODY-MASS INDEX; TRIAL; ANASTROZOLE; LETROZOLE; TAMOXIFEN C1 [Garber, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2013 VL 22 SU 1 BP S6 EP S6 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 126PZ UT WOS:000317634800012 ER PT J AU Goss, PE Badovinac-Crnjevic, T Fan, L AF Goss, P. E. Badovinac-Crnjevic, T. Fan, L. TI EXTENDED ADJUVANT ENDOCRINE THERAPY IN HORMONE-RECEPTOR POSITIVE BREAST CANCER SO BREAST LA English DT Meeting Abstract C1 [Goss, P. E.; Badovinac-Crnjevic, T.; Fan, L.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2013 VL 22 SU 1 BP S18 EP S18 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 126PZ UT WOS:000317634800039 ER PT J AU Harris, J AF Harris, J. TI HYPOFRACTIONATION IN THE ERA OF MODULATED RADIOTHERAPY SO BREAST LA English DT Meeting Abstract ID BREAST-CANCER C1 [Harris, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2013 VL 22 SU 1 BP S14 EP S14 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 126PZ UT WOS:000317634800030 ER PT J AU Partridge, AH AF Partridge, A. H. TI MANAGEMENT OF BREAST CANCER IN THE VERY YOUNG SO BREAST LA English DT Meeting Abstract ID WOMEN; PROGNOSIS; THERAPY C1 [Partridge, A. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2013 VL 22 SU 1 BP S18 EP S19 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 126PZ UT WOS:000317634800040 ER PT J AU Zhang, XL Ran, CZ AF Zhang, Xueli Ran, Chongzhao TI Dual Functional Small Molecule Probes as Fluorophore and Ligand for Misfolding Proteins SO CURRENT ORGANIC CHEMISTRY LA English DT Article DE Dual functional probes; Fluorescent probe; Misfolding proteins; Neurodegenerative disease; In vivo imaging; Fluorescent imaging; Near infrared imaging; Alzheimer's disease; Neurodegenerative diseases ID BETA-AMYLOID PLAQUES; IN-VIVO DETECTION; CERENKOV LUMINESCENCE TOMOGRAPHY; INSULIN GENE-TRANSCRIPTION; FIBRILLAR ALPHA-SYNUCLEIN; THIOFLAVIN-T BINDING; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; PARKINSONS-DISEASE; CONGO RED AB Misfolding of a protein is a destructive process for variety of diseases that include neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, Huntington disease, mad cow disease, amyotrophic lateral sclerosis (ALS), and frontal temporal dementia (FTD), and other non-CNS diseases such as diabetes, cystic fibrosis, and lysosomal storage diseases. Formation of various mis-functional large assembles of the misfolded protein is the primary consequence. To detect the formation of the aggregated species is very important for not only basic mechanism research but also very crucial for diagnosis of the diseases. In this review, we updated references related to the new development of the dual functional fluorescent small molecule probes for detecting the aggregated proteins in vitro and in vivo. C1 [Zhang, Xueli; Ran, Chongzhao] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab,Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02129 USA. [Zhang, Xueli] China Pharmaceut Univ, Sch Pharm, Ctr Drug Discovery, Nanjing, Jiangsu, Peoples R China. RP Ran, CZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab,Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Room 2301,Bldg 149, Boston, MA 02129 USA. EM cran@nmr.mgh.harvard.edu FU NIH/NIA [K25AG036760] FX This work was supported in part by NIH/NIA K25AG036760 award to C.R. We'd like to thank Pamela Pantazopoulos for proof-reading this manuscript. NR 121 TC 5 Z9 5 U1 1 U2 36 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1385-2728 J9 CURR ORG CHEM JI Curr. Org. Chem. PD MAR PY 2013 VL 17 IS 6 BP 580 EP 593 PG 14 WC Chemistry, Organic SC Chemistry GA 121WZ UT WOS:000317277000003 ER PT J AU Ibrahimi, OA Jalian, HR Shofner, JD Anderson, RR AF Ibrahimi, Omar A. Jalian, H. Ray Shofner, Josh D. Anderson, R. Rox TI Yellow Light Gone Wild: A Tale of Permanent Laser Hair Removal With a 595-nm Pulsed-Dye Laser SO JAMA DERMATOLOGY LA English DT Letter C1 [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT 06905 USA. [Ibrahimi, Omar A.; Jalian, H. Ray; Shofner, Josh D.; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Ibrahimi, OA (reprint author), Connecticut Skin Inst, 999 Summer St,Ste 205, Stamford, CT 06905 USA. EM omar.ibrahimi@gmail.com NR 4 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD MAR PY 2013 VL 149 IS 3 BP 376 EP 376 DI 10.1001/jamadermatol.2013.1300 PG 1 WC Dermatology SC Dermatology GA 127WJ UT WOS:000317729300026 PM 23553042 ER PT J AU Saltzman, JW Battaglino, RA Salles, L Jha, P Sudhakar, S Garshick, E Stott, HL Zafonte, R Morse, LR AF Saltzman, Jonah W. Battaglino, Ricardo A. Salles, Loise Jha, Prateek Sudhakar, Supreetha Garshick, Eric Stott, Helen L. Zafonte, Ross Morse, Leslie R. TI B-Cell Maturation Antigen, A Proliferation-Inducing Ligand, and B-Cell Activating Factor Are Candidate Mediators of Spinal Cord Injury-Induced Autoimmunity SO JOURNAL OF NEUROTRAUMA LA English DT Article DE autoimmunity; B cell; rehabilitation; spinal cord injury ID MYELIN BASIC-PROTEIN; CNS; AUTOANTIBODIES; SYSTEM; CYTOKINES; RESPONSES; MICE AB Autoimmunity is thought to contribute to poor neurological outcomes after spinal cord injury (SCI). There are few mechanism-based therapies, however, designed to reduce tissue damage and neurotoxicity after SCI because the molecular and cellular bases for SCI-induced autoimmunity are not completely understood. Recent groundbreaking studies in rodents indicate that B cells are responsible for SCI-induced autoimmunity. This novel paradigm, if confirmed in humans, could aid in the design of neuroprotective immunotherapies. The aim of this study was to investigate the molecular signaling pathways and mechanisms by which autoimmunity is induced after SCI, with the goal of identifying potential targets in therapies designed to reduce tissue damage and inflammation in the chronic phase of SCI. To that end, we performed an exploratory microarray analysis of peripheral blood mononuclear cells to identify differentially expressed genes in chronic SCI. We identified a gene network associated with lymphoid tissue structure and development that was composed of 29 distinct molecules and five protein complexes, including two cytokines, a proliferation-inducing ligand (APRIL) and B-cell-activating factor (BAFF), and one receptor, B-cell maturation antigen (BMCA) involved in B cell development, proliferation, activation, and survival. Real-time polymerase chain reaction analysis from ribonucleic acid samples confirmed upregulation of these three genes in SCI. To our knowledge, this is the first report that peripheral blood mononuclear cells produce increased levels of BAFF and APRIL in chronic SCI. This finding provides evidence of systemic regulation of SCI-autoimmunity via APRIL and BAFF mediated activation of B cells through BMCA and points toward these molecules as potential targets of therapies designed to reduce neuroinflammation after SCI. C1 [Saltzman, Jonah W.; Battaglino, Ricardo A.; Salles, Loise; Morse, Leslie R.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Battaglino, Ricardo A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02114 USA. [Salles, Loise] Univ Brasilia, Inst Biol, Dept Cell Biol, Brasilia, DF, Brazil. [Jha, Prateek; Sudhakar, Supreetha; Stott, Helen L.; Zafonte, Ross; Morse, Leslie R.] Spaulding Rehabil Hosp, Spauling Harvard Spinal Cord Injury Model Syst, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, Boston, MA USA. [Garshick, Eric] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02114 USA. [Zafonte, Ross; Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02114 USA. RP Morse, LR (reprint author), Harvard Univ, Sch Med, Dept PMR, Spaulding Harvard SCI Model Syst, 125 Nashua St, Boston, MA 02114 USA. EM lmorse4@partners.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU National Institute of Child Health and Human Development [R21HD057030, R21HD-057030-02S1]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270-02]; Department of Education [NIDRR H133N110010]; Office of Research and Development, Rehabilitation Research and Development [B6618R]; Massachusetts Veterans Epidemiology Research and Information Center, Cooperative Studies Program, Department of Veterans Affairs FX This study received support from the National Institute of Child Health and Human Development [R21HD057030 and R21HD-057030-02S1], the National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270-02], Department of Education, NIDRR H133N110010, the Office of Research and Development, Rehabilitation Research and Development [Merit Review Grant B6618R], and the Massachusetts Veterans Epidemiology Research and Information Center, Cooperative Studies Program, Department of Veterans Affairs. NR 30 TC 10 Z9 10 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD MAR PY 2013 VL 30 IS 6 BP 434 EP 440 DI 10.1089/neu.2012.2501 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 127ZK UT WOS:000317737400002 PM 23088438 ER PT J AU Cheung, WY Schaefer, K May, CW Glynn, RJ Curtis, LH Stevenson, LW Setoguchi, S AF Cheung, Winson Y. Schaefer, Kristen May, Christopher W. Glynn, Robert J. Curtis, Lesley H. Stevenson, Lynne W. Setoguchi, Soko TI Enrollment and Events of Hospice Patients With Heart Failure vs. Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Hospice; enrollment; heart failure; advanced cancer ID LUNG-CANCER; OF-LIFE; SYMPTOM BURDEN; CARE; END; PREFERENCES; DEATH; PROGNOSIS; QUALITY AB Context. Hospice care is traditionally used for patients with advanced cancer, but it is increasingly considered for patients with end-stage heart failure. Objectives. We compared enrollment patterns and clinical events of hospice patients with end-stage heart failure with those of patients with advanced cancer. Methods. Using Medicare data linked with pharmacy and cancer registry data, we identified patients who were diagnosed with either heart failure or advanced cancer between 1997 and 2004, admitted to hospice at least once after their diagnosis, and died during the study period. We compared patterns of referral, use of acute services, and site of death of hospice patients with heart failure with those of patients with advanced cancer. Logistic regression models were constructed to determine the factors associated with late hospice enrollment as well as the use of and death in acute care. Results. We identified 1580 heart failure patients and 3840 advanced cancer patients: mean ages were 86 and 80 years, 82% and 68% were women, and 97% and 94% were white, respectively. Compared with patients with advanced cancer, those with heart failure were more frequently referred to hospice from hospitals (35% vs. 24%) and nursing facilities (9% vs. 7%) (both P < 0.01). Discharge from hospice before death was similar for patients with heart failure and patients with advanced cancer (10% vs. 9%, P = 0.03). Among patients remaining in hospice, patients with heart failure were more likely to have been enrolled within three days of death (20% vs. 11%, P < 0.01). The prevalence of death in acute care settings was low in both groups after hospice enrollment (4% heart failure vs. 2% advanced cancer, P < 0.01). Although the median interval between enrollment and death was shorter for heart failure patients (12 vs. 20 days, P < 0.001), emergency department visits and hospitalizations after hospice enrollment were more frequent in patients with heart failure (13% vs. 10% and 9% vs. 6%, respectively, both P < 0.01). Conclusion. Compared with patients with advanced cancer, referral to hospice is more often initiated during acute care encounters for patients with end-stage heart failure, who also more frequently return to acute care settings even after hospice enrollment. J Pain Symptom Manage 2013;45:552-560. (C) 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Cheung, Winson Y.] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Schaefer, Kristen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Glynn, Robert J.; Stevenson, Lynne W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [May, Christopher W.; Curtis, Lesley H.; Setoguchi, Soko] Duke Clin Res Inst, Durham, NC USA. RP Cheung, WY (reprint author), British Columbia Canc Agcy, Div Med Oncol, 600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM wcheung@bccancer.bc.ca NR 25 TC 8 Z9 8 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 2013 VL 45 IS 3 BP 552 EP 560 DI 10.1016/j.jpainsymman.2012.03.006 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 123SV UT WOS:000317412000011 PM 22940560 ER PT J AU Ahmad, S Wei, CC Tallaj, J Dell'Italia, LJ Moniwa, N Varagic, J Ferrario, CM AF Ahmad, Sarfaraz Wei, Chih-Chang Tallaj, Jose Dell'Italia, Louis J. Moniwa, Norihito Varagic, Jasmina Ferrario, Carlos M. TI Chymase mediates angiotensin-(1-12) metabolism in normal human hearts SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE ACE2; cardiac myocytes; angiotensin-converting enzyme inhibitors; angiotensin II; heart disease; proangiotensin 12; angiotensin-(1-7) ID II-FORMING CHYMASE; CONVERTING ENZYME; INDEPENDENT MECHANISMS; PROANGIOTENSIN-12 PA12; CARBOXYPEPTIDASE ACE2; MITRAL REGURGITATION; ATRIAL-FIBRILLATION; PEPTIDE METABOLISM; SYSTEM; INHIBITION AB Identification of angiotensin-(1-12) [Ang-(1-12)] in forming angiotensin II (Ang II) by a non-renin dependent mechanism has increased knowledge on the paracrine/autocrine mechanisms regulating cardiac expression of Ang peptides. This study now describes in humans the identity of the enzyme accounting for Ang-(1-12) metabolism in the left ventricular (LV) tissue of normal subjects. Reverse phase HPLC characterized the products of I-125-Ang-(1-12) metabolism in plasma membranes (PMs) from human LV in the absence and presence of inhibitors for chymase (chymostatin), angiotensin-converting enzyme (ACE) 1 (lisinopril) and 2 (MLN-4760), and neprilysin (SHC39370). In the presence of the inhibitor cocktail, >= 98% +/- 2% of cardiac I-125-Ang-(1-12) remained intact, whereas exclusion of chymostatin from the inhibitor cocktail led to significant conversion of Ang-(1-12) into Ang II. In addition, chymase-mediated hydrolysis of I-125-Ang I was higher compared with Ang-(1-12). Negligible Ang-(1-12) hydrolysis occurred by ACE, ACE2, and neprilysin. A high chymase activity was detected for both I-125-Ang-(1-12) and I-125-Ang I substrates. Chymase accounts for the conversion of Ang-(1-12) and Ang I to Ang II in normal human LV. These novel findings expand knowledge of the alternate mechanism by which Ang-(1-12) contributes to the production of cardiac angiotensin peptides. J Am Soc Hypertens 2013;7(2):128-136. (C) 2013 American Society of Hypertension. All rights reserved. C1 [Ahmad, Sarfaraz; Moniwa, Norihito; Varagic, Jasmina; Ferrario, Carlos M.] Wake Forest Univ, Bowman Gray Sch Med, Div Surg Sci, Winston Salem, NC 27157 USA. [Wei, Chih-Chang; Tallaj, Jose; Dell'Italia, Louis J.] Univ Alabama Birmingham, Med Ctr, Birmingham Vet Affair Med Ctr, Birmingham, AL 35294 USA. [Wei, Chih-Chang; Tallaj, Jose; Dell'Italia, Louis J.] Univ Alabama Birmingham, Med Ctr, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Varagic, Jasmina] Wake Forest Univ, Bowman Gray Sch Med, Hypertens & Vasc Res Ctr, Winston Salem, NC 27157 USA. [Varagic, Jasmina; Ferrario, Carlos M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. [Ferrario, Carlos M.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. RP Ferrario, CM (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Surg, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM cferrari@wakehealth.edu FU Heart, Lung, Blood Institute of the National Institutes of Health [HL-051952]; Farley-Hudson Foundation, Jacksonville, NC FX Supported by a grant (HL-051952) from the Heart, Lung, Blood Institute of the National Institutes of Health. We also acknowledge partial support provided by the Farley-Hudson Foundation, Jacksonville, NC. NR 47 TC 17 Z9 17 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD MAR-APR PY 2013 VL 7 IS 2 BP 128 EP 136 DI 10.1016/j.jash.2012.12.003 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 120KI UT WOS:000317168800004 PM 23312967 ER PT J AU Malte, CA McFall, M Chow, B Beckham, JC Carmody, TP Saxon, AJ AF Malte, Carol A. McFall, Miles Chow, Bruce Beckham, Jean C. Carmody, Timothy P. Saxon, Andrew J. TI Survey of Providers' Attitudes Toward Integrating Smoking Cessation Treatment Into Posttraumatic Stress Disorder Care SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE smoking cessation; posttraumatic stress disorder; veterans; mental health providers; provider survey; implementation ID MENTAL-HEALTH-CARE; TOBACCO CESSATION; NICOTINE DEPENDENCE; PARIHS FRAMEWORK; VETERANS; IMPLEMENTATION; PREVALENCE; ADDICTION; ILLNESS AB A survey was administered anonymously to 45 mental health providers who delivered smoking cessation treatment integrated into posttraumatic stress disorder care (integrated care) as part of a multisite clinical trial. Survey items assessed key factors associated with successful implementation of research-based practices from the perspective of treating providers. Factors assessed included prior experiences with cessation treatment, compatibility of integrated care with current practices, feasibility of adopting integrated care into regular practice, and adequacy of training. More than half of respondents reported that integrated care delivery was feasible, and they would be considerably or extremely likely to continue delivery in routine practice. Positive prestudy beliefs and more experience delivering cessation care were associated with stronger endorsement of delivering integrated care after the study. The most frequently cited obstacle to delivering integrated care involved time limitations. Future efforts should focus on developing treatment adaptations that address provider-identified barriers and identifying clinic- and administrative-level supports that facilitate delivery of integrated care and assist providers who incorporate integrated care into clinical practice. C1 [Malte, Carol A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA USA. [McFall, Miles; Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [McFall, Miles; Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Chow, Bruce] Vet Affairs Palo Alto Hlth Care Syst, Vet Affairs Cooperat Studies Program, Palo Alto, CA USA. [Beckham, Jean C.] Vet Affairs Mid Atlantic Reg Mental Illness Res E, Durham Vet Affairs Med Ctr, Durham, NC USA. [Beckham, Jean C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. [Carmody, Timothy P.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Carmody, Timothy P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Malte, CA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116 ATC, Seattle, WA 98108 USA. EM carol.malte@va.gov NR 29 TC 2 Z9 2 U1 0 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD MAR PY 2013 VL 27 IS 1 BP 249 EP 255 DI 10.1037/a0028484 PG 7 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 107RH UT WOS:000316238000029 PM 22642854 ER PT J AU Emery, MJ Eveland, RL Min, JH Hildebrandt, J Swenson, ER AF Emery, Michael J. Eveland, Randy L. Min, Jin-Hye Hildebrandt, Jacob Swenson, Erik R. TI CO2 relaxation of the rat lung parenchymal strip SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE Alveolar; Pulmonary mechanics; Ventilation-to-perfusion matching; Myosin ID AIRWAY SMOOTH-MUSCLE; HYPOXIC PULMONARY VASOCONSTRICTION; STIMULUS-RESPONSE; TISSUE RESISTANCE; MYOSIN-V; CALCIUM; DISSOCIATION; CONTRACTION; TENSION; OXYGEN AB Evidence from liquid-filled rat lungs supported the presence of CO2-dependent, active relaxation of parenchyma under normoxia by unknown mechanisms (Emery et al., 2007). This response may improve matching of alveolar ventilation ((V) over dot(A)) to perfusion ((Q) over dot) by increasing compliance and (V) over dot(A) in overperfused (high CO2) regions, and decrease (V) over dot(A) in underperfused regions. Here, we have more directly studied CO2-dependent parenchymal relaxation and tested a hypothesized role for actin-myosin interaction in this effect. Lung parenchymal strips (similar to 1.5 mm x 1.5 mm x 15 mm) from 16 rats were alternately exposed to normoxic hypocapnia (P-CO2 approximate to 20 mmHg) or hypercapnia (P-CO2 approximate to 53 mmHg). Seven specimens were used to construct length-tension curves, and nine were tested with and without the myosin blocker 2,3-butanedione monoxime (BDM). The results demonstrate substantial, reversible CO2-dependent changes in parenchyma strip recoil (up to 23%) and BDM eliminates this effect, supporting a potentially important role for parenchymal myosin in (V) over dot(A)/(Q) over dot matching. Published by Elsevier B.V. C1 [Emery, Michael J.; Eveland, Randy L.; Min, Jin-Hye; Swenson, Erik R.] VA Puget Sound Hlth Care Syst, Pulm & Crit Care Med S PULM 111, Seattle, WA 98108 USA. [Hildebrandt, Jacob; Swenson, Erik R.] Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Hildebrandt, Jacob; Swenson, Erik R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Emery, MJ (reprint author), VA Puget Sound Hlth Care Syst, Pulm & Crit Care Med S PULM 111, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mjemery@u.washington.edu; jackhil@u.washington.edu; eswenson@u.washington.edu FU VA Merit Review FX The authors gratefully acknowledge Steve Lai-Fook for important conversations concerning quantification of lung mechanical characteristics, Linda Wordeman for important conversations concerning inhibition of contractile proteins, and Albert Gordon for use of essential test equipment. Support for this project was provided by a VA Merit Review awarded to Erik R. Swenson. NR 39 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD MAR 1 PY 2013 VL 186 IS 1 BP 33 EP 39 DI 10.1016/j.resp.2012.12.014 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 124EW UT WOS:000317447600005 PM 23305910 ER PT J AU Balaban, DY Duffin, J Preiss, D Mardimae, A Vesely, A Slessarev, M Zubieta-Calleja, GR Greene, ER MacLeod, DB Fisher, JA AF Balaban, Dahlia Y. Duffin, James Preiss, David Mardimae, Alexandra Vesely, Alex Slessarev, Marat Zubieta-Calleja, G. R. Greene, Ernest R. MacLeod, David B. Fisher, Joseph A. TI The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE Carbon dioxide; Hypoxia; Haemoglobin oxygen saturation; O-2 dissociation curve; Humans; Andeans; High altitude ID OXYGEN-AFFINITY; TIBETAN HIGHLANDERS; NATURAL-SELECTION; PULSE OXIMETER; HEMOGLOBIN; BLOOD; ERYTHROCYTE; ADAPTATION; TRANSPORT; EQUILIBRIUM AB Animals native to hypoxic environments have adapted by increasing their haemoglobin oxygen affinity, but in-vitro studies of the oxyhaemoglobin dissociation curve (ODC) in humans show no changes in affinity under physiological conditions at altitudes up to 4000 m. We conducted the first in-vivo measurement of the ODC; inducing progressive isocapnic hypoxia in lowlanders at sea level, acutely acclimatized lowlanders at 3600m, and native Andeans at that altitude. ODC curves were determined by administering isocapnic steps of increasing hypoxia, and measuring blood oxygen partial pressure and saturation. The ODC data were fitted using the Hill equation and extrapolated to predict the oxygen partial pressure at which haemoglobin was 50% saturated (P-50). In contrast to findings from in-vitro studies, we found a pH-related reduction in P-50 in subjects at altitude, compared to sea-level subjects. We conclude that a pH-mediated increase in haemoglobin oxygen affinity in-vivo may be part of the acclimatization process in humans at altitude. (C) 2013 Elsevier B.V. All rights reserved. C1 [Balaban, Dahlia Y.; Fisher, Joseph A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada. [Duffin, James; Fisher, Joseph A.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. [Duffin, James; Mardimae, Alexandra; Fisher, Joseph A.] Univ Toronto, Dept Anaesthesiol, Toronto, ON M5S 1A8, Canada. [Duffin, James; Mardimae, Alexandra; Fisher, Joseph A.] Univ Hlth Network, Toronto, ON, Canada. [Preiss, David] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Vesely, Alex] Univ British Columbia, Dept Anesthesiol Pharmacol & Therapeut, Vancouver, BC V6T 1Z3, Canada. [Slessarev, Marat] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. [Zubieta-Calleja, G. R.] High Altitude Pathol Inst, La Paz, Bolivia. [Greene, Ernest R.] New Mexico Highlands Univ, Las Vegas, NM 87701 USA. [MacLeod, David B.] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. RP Duffin, J (reprint author), Thornhill Res Inc, 210 Dundas St W Suite 200, Toronto, ON M5G 2E8, Canada. EM j.duffin@utoronto.ca OI Balaban, Dahlia/0000-0002-8521-2402; Duffin, James/0000-0003-2270-7392 NR 37 TC 7 Z9 9 U1 3 U2 41 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD MAR 1 PY 2013 VL 186 IS 1 BP 45 EP 52 DI 10.1016/j.resp.2012.12.011 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 124EW UT WOS:000317447600007 PM 23313855 ER PT J AU Jalian, HR Avram, MM AF Jalian, H. Ray Avram, Mathew M. TI Cryolipolysis: A Historical Perspective and Current Clinical Practice SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article DE cryolipolysis; cryotherapy; body contouring; fat; panniculitis ID COLD PANNICULITIS; NONINVASIVE CRYOLIPOLYSIS AB Dermatologists have long used cold-based therapeutic approaches for a variety of applications. Based on the differences in chemical composition, it is possible to selectively target certain tissues rich with lipid, while sparing the surrounding tissue predominantly containing water. With historical observations of cold-induced panniculitis suggesting the feasibility of this strategy, cryolipolysis has emerged as a new methodology using controlled cooling to selectively target fat. Both preclinical and clinical studies have established the safety and efficacy of cryolipolysis for noninvasive body contouring. This review will focus on the evolution of cryolipolysis from initial case reports of cold-induced panniculitis, to preclinical and clinical studies, and the current clinical practice. Semin Cutan Med Surg 32:31-34 (C) 2013 Frontline Medical Communications C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser & Cosmet Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Jalian, HR (reprint author), Massachusetts Gen Hosp, Dermatol Laser & Cosmet Ctr, Wellman Ctr Photomed, 40 Blossom St,Room 204, Boston, MA 02114 USA. EM HJalian@partners.org NR 20 TC 8 Z9 8 U1 1 U2 14 PU FRONTLINE MEDICAL COMMUNICATIONS PI THE WOODLANDS PA WRIGHTS MEDIA, 2407 TIMBERLOCH PLACE, SUITE B, THE WOODLANDS, TX 77386 USA SN 1085-5629 EI 1558-0768 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD MAR PY 2013 VL 32 IS 1 BP 31 EP 34 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 125GX UT WOS:000317529400006 PM 24049927 ER PT J AU Avci, P Gupta, A Sadasivam, M Vecchio, D Pam, Z Pam, N Hamblin, MR AF Avci, Pinar Gupta, Asheesh Sadasivam, Magesh Vecchio, Daniela Pam, Zeev Pam, Nadav Hamblin, Michael R. TI Low-Level Laser (Light) Therapy (LLLT) in Skin: Stimulating, Healing, Restoring SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID HELIUM-NEON LASER; HERPES-SIMPLEX-VIRUS; CYTOCHROME-C-OXIDASE; EXTRACELLULAR-MATRIX PROTEINS; IL-6 SIGNALING PATHWAY; BIPHASIC DOSE-RESPONSE; IN-VITRO; ACNE-VULGARIS; INFRARED RADIATION; HYPERTROPHIC SCARS AB Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require stimulation of healing, relief of pain and inflammation, and restoration of function. Although skin is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths. The photons are absorbed by mitochondrial chromophores in skin cells. Consequently, electron transport, adenosine triphosphate nitric oxide release, blood flow, reactive oxygen species increase, and diverse signaling pathways are activated. Stem cells can be activated, allowing increased tissue repair and healing. In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a treatment and as a prophylactic measure. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also be managed. The noninvasive nature and almost complete absence of side effects encourage further testing in dermatology. Semin Cutan Med Surg 32:41-52 (C) 2013 Frontline Medical Communications C1 [Avci, Pinar; Gupta, Asheesh; Sadasivam, Magesh; Vecchio, Daniela; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Avci, Pinar; Gupta, Asheesh; Sadasivam, Magesh; Vecchio, Daniela; Hamblin, Michael R.] Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02114 USA. [Gupta, Asheesh] Def Inst Physiol & Allied Sci, Delhi, India. [Sadasivam, Magesh; Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Pam, Zeev; Pam, Nadav] Aripam Med Ctr, Ashdod, Israel. RP Hamblin, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Ctr Photomed, BAR 414 Wellman,40 Blossom St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875]; Boycast Fellowship, Rolo 11, in India FX This work was supported by the US NIH (R01AI050875 to MRH).; Dr Asheesh Gupta has recieved a grant from Boycast Fellowship, Rolo 11, in India. NR 117 TC 74 Z9 74 U1 9 U2 49 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD MAR PY 2013 VL 32 IS 1 BP 41 EP 52 PG 12 WC Dermatology; Surgery SC Dermatology; Surgery GA 125GX UT WOS:000317529400008 PM 24049929 ER PT J AU Kleinerman, R Eisen, DB Kilmer, SL Ibrahimi, OA AF Kleinerman, Rebecca Eisen, Daniel B. Kilmer, Suzanne L. Ibrahimi, Omar A. TI The New Age of Noninvasive Facial Rejuvenation SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article DE nonablative fractional resurfacing; ablative fractional resurfacing; antiaging ID CARBON-DIOXIDE LASER; INTENSE PULSED-LIGHT; FRACTIONAL RESURFACING DEVICE; THULIUM FIBER LASER; TOPICAL VITAMIN-C; ERBIUM-YAG LASER; SIDE-BY-SIDE; ALEXANDRITE LASER; DYE-LASER; SPLIT-FACE AB The techniques of noninvasive facial rejuvenation are forever being redefined and improved. This article will review historical as well as present approaches to resurfacing, discussing the nonablative tools that can complement resurfacing procedures. Current thoughts on the pre- and postoperative care of resurfacing patients are also considered. Semin Cutan Med Surg 32:53-58 (C) 2013 Frontline Medical Communications C1 [Kleinerman, Rebecca] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. [Kleinerman, Rebecca] Schweiger Dermatol, New York, NY USA. [Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Kilmer, Suzanne L.] Laser & Skin Surg Ctr Northern Calif, Sacramento, CA USA. [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT 06905 USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Ibrahimi, OA (reprint author), Connecticut Skin Inst, 999 Summer St, Stamford, CT 06905 USA. EM omar.ibrahimi@gmail.com NR 69 TC 1 Z9 1 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD MAR PY 2013 VL 32 IS 1 BP 53 EP 58 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 125GX UT WOS:000317529400009 PM 24049930 ER PT J AU Cordell, CB Borson, S Boustani, M Chodosh, J Reuben, D Verghese, J Thies, W Fried, LB AF Cordell, Cyndy B. Borson, Soo Boustani, Malaz Chodosh, Joshua Reuben, David Verghese, Joe Thies, William Fried, Leslie B. CA Medicare Detection Cognitive TI Alzheimer's Association recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting SO ALZHEIMERS & DEMENTIA LA English DT Article DE Annual Wellness Visit; AWV; Cognitive impairment; Assessment; Screen; Dementia; Alzheimer's disease; Medicare; Algorithm; Patient Protection and Affordable Care Act ID MINI-MENTAL-STATE; MEMORY IMPAIRMENT; SCREENING-TEST; VULNERABLE ELDERS; CONTROLLED-TRIAL; DEMENTIA CARE; OLDER-ADULTS; INFORMANT; DISEASE; VALIDATION AB The Patient Protection and Affordable Care Act added a new Medicare benefit, the Annual Wellness Visit (AWV), effective January 1, 2011. The AWV requires an assessment to detect cognitive impairment. The Centers for Medicare and Medicaid Services (CMS) elected not to recommend a specific assessment tool because there is no single, universally accepted screen that satisfies all needs in the detection of cognitive impairment. To provide primary care physicians with guidance on cognitive assessment during the AWV, and when referral or further testing is needed, the Alzheimer's Association convened a group of experts to develop recommendations. The resulting Alzheimer's Association Medicare Annual Wellness Visit Algorithm for Assessment of Cognition includes review of patient Health Risk Assessment (HRA) information, patient observation, unstructured queries during the AWV, and use of structured cognitive assessment tools for both patients and informants. Widespread implementation of this algorithm could be the first step in reducing the prevalence of missed or delayed dementia diagnosis, thus allowing for better healthcare management and more favorable outcomes for affected patients and their families and caregivers. (c) 2013 The Alzheimer's Association. All rights reserved. C1 [Cordell, Cyndy B.; Thies, William] Alzheimers Assoc, Chicago, IL 60601 USA. [Borson, Soo] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Borson, Soo] Univ Washington, Sch Med, Memory Disorders Clin, Seattle, WA USA. [Borson, Soo] Univ Washington, Sch Med, Dementia Hlth Serv, Seattle, WA USA. [Boustani, Malaz] Indiana Univ, Ctr Aging Res, Indianapolis, IN 46204 USA. [Boustani, Malaz] Regenstrief Inst Inc, Indianapolis, IN USA. [Boustani, Malaz] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA. [Chodosh, Joshua] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chodosh, Joshua; Reuben, David] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Verghese, Joe] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Fried, Leslie B.] Amer Bar Assoc, Washington, DC 20013 USA. [Fried, Leslie B.] Alzheimers Assoc Medicare Advocacy Project, Washington, DC USA. RP Cordell, CB (reprint author), Alzheimers Assoc, Chicago, IL 60601 USA. EM cyndy.cordell@alz.org OI Chodosh, Joshua/0000-0001-7784-4306 NR 60 TC 80 Z9 81 U1 6 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAR PY 2013 VL 9 IS 2 BP 141 EP 150 DI 10.1016/j.jalz.2012.09.011 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 119JD UT WOS:000317092700006 PM 23265826 ER PT J AU Mooney, LJ Nielsen, S Saxon, A Hillhouse, M Thomas, C Hasson, A Stablein, D McCormack, J Lindblad, R Ling, W AF Mooney, Larissa J. Nielsen, Suzanne Saxon, Andrew Hillhouse, Maureen Thomas, Christie Hasson, Albert Stablein, Don McCormack, Jennifer Lindblad, Robert Ling, Walter TI Cocaine Use Reduction with Buprenorphine (CURB): Rationale, design, and methodology SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Cocaine dependence; Buprenorphine; Naltrexone; Clinical Trials Network; Methods; Kappa antagonist ID OF-LIFE ASSESSMENT; PSYCHOMETRIC PROPERTIES; OPIOID DEPENDENCE; ANTAGONIST; SUBSTANCE; TRIAL; TIME AB Background: Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone (R)) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol (R)) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. Methods: This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Conclusions: This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. (C) 2012 Elsevier Inc. All rights reserved. C1 [Mooney, Larissa J.; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ling, Walter] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA. [Nielsen, Suzanne] Univ Sydney, Drug Hlth Serv C39, Sydney, NSW 2006, Australia. [Saxon, Andrew] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Saxon, Andrew] Univ Washington, Seattle, WA 98108 USA. [Stablein, Don; McCormack, Jennifer; Lindblad, Robert] EMMES Corp, Rockville, MD 20850 USA. RP Mooney, LJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Integrated Subst Abuse Programs, 1640 S Sepulveda Blvd,Suite 120, Los Angeles, CA 90025 USA. EM lmooney@mednet.ucla.edu; suzanne.nielsen@sydney.edu.au; andrew.saxon@va.gov; hillhous@ucla.edu; cthomas@friendsresearch.org; alhasson@ucla.edu; dstablein@emmes.com; jmccormack@emmes.com; rlindblad@emmes.com; lwalter@ucla.edu RI Nielsen, Suzanne/C-3256-2015 OI Nielsen, Suzanne/0000-0001-5341-1055 FU National Institute on Drug Abuse Clinical Trials Network [U10DA013045, U10DA01714]; NIDA [N01DA92217, N01DA102221] FX This work was supported by the National Institute on Drug Abuse Clinical Trials Network Grants U10DA013045 (ISAP, Pacific Region Node); U10DA01714 (RCKC, Pacific Northwest Node); and NIDA Contracts N01DA92217 and N01DA102221 (The EMMES Corporation). We thank the staff and participants at the community treatment programs and regional research and training centers of the National Institute on Drug Abuse Clinical Trials Network for their involvement in this project, including Albert Einstein College of Medicine (Greater New York Node), Bellevue Hospital Center (Greater New York Node), Addiction Research & Treatment Services (Western States Node), CODA, Inc. (Western States Node), Atlanta VA Medical Center (Southern Consortium Node), Howard University (Mid-Atlantic Node), Maryhaven (Ohio Valley Node), Recovery Centers of King County (Pacific Northwest Node), South Texas Veterans Health Care System (Texas Node), Bay Area Addiction Research and Treatment (Pacific Region Node), and UCLA Integrated Substance Abuse Programs (Pacific Region Node). We also thank the staff of the Clinical Coordinating Center and the Data Coordinating Center (The EMMES Corporation, Rockville, MD), and the staff of the Center for the Clinical Trials Network at the National Institute on Drug Abuse (Rockville, MD) for their work on this project. NR 30 TC 11 Z9 13 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAR PY 2013 VL 34 IS 2 BP 196 EP 204 DI 10.1016/j.cct.2012.11.002 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 120KL UT WOS:000317169100002 PM 23159524 ER PT J AU Singh, H Singh, P Kumari, K Chandra, A Dass, SK Chandra, R AF Singh, Harpal Singh, Prashant Kumari, Kamlesh Chandra, Ankush Dass, Sujata K. Chandra, Ramesh TI A Review on Noscapine, and its Impact on Heme Metabolism SO CURRENT DRUG METABOLISM LA English DT Review DE L-(S,R) Noscapine; glutathione S-transferases (GSTs); cytochrome P-450; biliverdin; alanine transaminase (ALT); and bilirubin ID HUMAN OVARIAN-CANCER; MICROTUBULE DYNAMICS; LEUKEMIC-CELLS; APOPTOSIS; GLUTATHIONE; AGENTS; DRUG; TUMORS; PHARMACOKINETICS; CARCINOGENESIS AB This review introduces the Noscapine, which is being used as an antitussive drug for a long time has been recently discovered as a novel tubulin-binding, anti-angiogenic anticancer drug that causes cell cycle arrest and induces apoptosis in cancer cells both in vitro as well as in vivo. Noscapine is a multifunctional molecule i.e. it possesses various functional moieties. We maneuvered various amenable sites and have synthesized analogs, which might prove to be more efficacious and less cytotoxic. Moreover, development of oral controlled release anticancer formulation of noscapine is severely hampered due to short biological half-life (< 2-h), poor absorption, low aqueous solubility, and extensive first pass metabolism, thereby requiring large doses for effective treatment. C1 [Singh, Harpal; Singh, Prashant; Chandra, Ramesh] Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, Delhi 110007, India. [Singh, Prashant] BBA Univ, Dept Appl Chem, Lucknow, Uttar Pradesh, India. [Singh, Prashant] Univ Delhi, ARSD Coll, New Delhi, India. [Kumari, Kamlesh] MNNIT, Dept Chem, Allahabad, Uttar Pradesh, India. [Chandra, Ankush] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Dass, Sujata K.] Univ Delhi, VP Chest Inst, Delhi 110007, India. RP Chandra, R (reprint author), Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, Delhi 110007, India. EM arsdchemistry@yahoo.in FU UGC, New Delhi, India FX The author (Dr. Prashant Singh) is thankful to UGC, New Delhi, India, for providing the funding. NR 65 TC 8 Z9 8 U1 3 U2 26 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD MAR PY 2013 VL 14 IS 3 BP 351 EP 360 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 119SR UT WOS:000317118400010 PM 22935070 ER PT J AU Garibyan, L Rheingold, CG Lerner, EA AF Garibyan, Lilit Rheingold, Curtis G. Lerner, Ethan A. TI Understanding the pathophysiology of itch SO DERMATOLOGIC THERAPY LA English DT Article DE itch; mediator; neuron; pruritus ID HISTAMINE H-4 RECEPTOR; HUMAN SKIN; BRACHIORADIAL PRURITUS; ATOPIC-DERMATITIS; T-CELLS; POSTHERPETIC NEURALGIA; NOTALGIA-PARESTHETICA; CUTANEOUS INNERVATION; SUBSTANCE-P; MAST-CELLS AB Itch is the most common symptom described by our patients. Treating this symptom can be challenging. A revolution is ongoing in understanding the pathophysiology of itch and will allow this challenge to be met. The present authors review and update the current understanding of the pathophysiology of itch. C1 [Garibyan, Lilit; Rheingold, Curtis G.; Lerner, Ethan A.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp, Dermatol Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM elerner@partners.org FU NIH [R01AR057744] FX The present authors thank Dr. Sarina Elmariah for helpful comments. This work was supported by NIH grant R01AR057744 to E. A. L. NR 59 TC 13 Z9 16 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAR-APR PY 2013 VL 26 IS 2 SI SI BP 84 EP 91 DI 10.1111/dth.12025 PG 8 WC Dermatology SC Dermatology GA 119WN UT WOS:000317130100002 PM 23551365 ER PT J AU Garibyan, L Chiou, AS Elmariah, SB AF Garibyan, Lilit Chiou, Albert S. Elmariah, Sarina B. TI Advanced aging skin and itch: addressing an unmet need SO DERMATOLOGIC THERAPY LA English DT Article DE elderly; pruritus; Willan's itch; xerosis ID EPIDERMAL PERMEABILITY BARRIER; TRIGEMINAL TROPHIC SYNDROME; HEMODIALYSIS-PATIENTS; NEUROPATHIC PRURITUS; GROVERS-DISEASE; WALLENBERG SYNDROME; CONTROLLED-TRIAL; UREMIC PRURITUS; LIVER-DISEASE; GABAPENTIN AB Itch is the most common skin disorder in the elderly and frequently diminishes quality of life in this population. The high prevalence of pruritus in elderly patients is attributed in part to the decline in the normal physiology of the advanced aging skin, and reflects poor hydration, impaired skin barrier, and altered neural function, all ultimately contributing to inflammation and pruritus. As the elderly population continues to grow, practitioners need to be aware of how to evaluate and manage pruritus, recognizing the common conditions contributing to itch in elderly patients as well as the challenges of treatment in this group. Ultimately, management of pruritus will require an individually tailored approach that is guided by a patient's general health, severity of symptoms, and the potential adverse effects of itch therapies. C1 [Garibyan, Lilit; Chiou, Albert S.; Elmariah, Sarina B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Elmariah, SB (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, 149 13th St, Charlestown, MA 02129 USA. EM sbelmariah@partners.org FU NIAMS NIH HHS [T32 AR007098] NR 74 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAR-APR PY 2013 VL 26 IS 2 SI SI BP 92 EP 103 DI 10.1111/dth.12029 PG 12 WC Dermatology SC Dermatology GA 119WN UT WOS:000317130100003 PM 23551366 ER PT J AU Pfab, F Schalock, PC Napadow, V Athanasiadis, GI Yosipovitch, G Ring, J AF Pfab, F. Schalock, P. C. Napadow, V. Athanasiadis, G. I. Yosipovitch, G. Ring, J. TI Complementary integrative approach for treating pruritus SO DERMATOLOGIC THERAPY LA English DT Article DE pruritus; complementary; itch; acupuncture; alternative ID HISTAMINE-INDUCED ITCH; TRADITIONAL CHINESE MEDICINE; RANDOMIZED CONTROLLED-TRIAL; I HYPERSENSITIVITY ITCH; ATOPIC-DERMATITIS; DOUBLE-BLIND; ANALGESIC REQUIREMENT; CROSSOVER TRIAL; NEUROGENIC INFLAMMATION; THERAPEUTIC APPROACH AB Complementary and alternative medicine (CAM) is a conservative and increasingly popular approach to treat pruritus for both patients and medical providers. CAM includes natural products, mindbody medicine, and manipulative and body-based practices. In this overview, we summarize current evidence, possible mechanisms and clinical approaches for treating pruritus with CAM techniques. We focus on pruritus associated with atopic dermatitis, herpes zoster, chronic urticaria, burns, and postoperative contexts where the evidence for CAM approaches is promising. C1 [Pfab, F.; Athanasiadis, G. I.; Ring, J.] Tech Univ Munich, Dept Dermatol & Allergy, D-80290 Munich, Germany. [Pfab, F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Prevent & Sports Med, Charlestown, MA USA. [Pfab, F.; Napadow, V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Schalock, P. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Napadow, V.] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Yosipovitch, G.] Wake Forest Univ Hlth Sci, Dept Dermatol Neurobiol & Anat, Winston Salem, NC USA. RP Pfab, F (reprint author), Tech Univ Munich, Dept Dermatol & Allergy, D-80290 Munich, Germany. EM florian.pfab@lrz.tum.de OI Schalock, Peter/0000-0001-8953-4639 NR 83 TC 5 Z9 5 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD MAR-APR PY 2013 VL 26 IS 2 SI SI BP 149 EP 156 DI 10.1111/dth.12031 PG 8 WC Dermatology SC Dermatology GA 119WN UT WOS:000317130100008 PM 23551371 ER PT J AU Leone, V Chang, EB Devkota, S AF Leone, Vanessa Chang, Eugene B. Devkota, Suzanne TI Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases SO JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Inflammatory bowel diseases; Pathobiont; Western diet; Gut microbiota ID GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; DEFICIENT MICE; COLITIS; EPIDEMIOLOGY; PREVALENCE; BACTERIA; POPULATION; ANTIBODIES; EVOLUTION AB The incidence of inflammatory bowel diseases (IBD), as well as other inflammatory conditions, has dramatically increased over the past half century. While many studies have shown that IBD exhibits a genetic component via genome-wide association studies, genetic drift alone cannot account for this increase, and other factors, such as those found in the environment must play a role, suggesting a "multiple hit" phenomenon that precipitates disease. One major environmental factor, dietary intake, has shifted to a high fat, high carbohydrate Western-type diet in developing nations, nearly in direct correlation with the increasing incidence of IBD. Recent evidence suggests that specific changes in dietary intake have led to a shift in the composite human gut microbiota, resulting in the emergence of pathobionts that can thrive under specific conditions. In the genetically susceptible host, the emerging pathobionts can lead to increasing incidence and severity of IBD and other inflammatory disorders. Since the gut microbiota is plastic and responds to dietary modulations, the use of probiotics, prebiotics, and/or dietary alterations are all intriguing complementary therapeutic approaches to alleviate IBD symptoms. However, the interactions are complex and it is unlikely that a one-size-fits all approach can be utilized across all populations affected by IBD. Exploration into and thoroughly understanding the interactions between host and microbes, primarily in the genetically susceptible host, will help define strategies that can be tailored to an individual as we move towards an era of personalized medicine to treat IBD. C1 [Leone, Vanessa; Chang, Eugene B.] Univ Chicago, Dept Med Gastroenterol Hepatol & Nutr, Chicago, IL 60637 USA. [Devkota, Suzanne] Harvard Univ, Sch Med, Dept Med, Res Div,Joslin Diabet Ctr, Boston, MA 02215 USA. RP Devkota, S (reprint author), Harvard Univ, Sch Med, Dept Med, Res Div,Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Suzanne.Devkota@joslin.harvard.edu FU NIH/NIDDK [P30DK42086, UH3DK083993, DK097268, T32DK07074]; NIH/NCAAM [F31AT00607] FX The authors acknowledge support from NIH/NIDDK research grants, P30DK42086, UH3DK083993, DK097268, and T32DK07074; NIH/NCAAM research grant F31AT00607. NR 50 TC 49 Z9 50 U1 2 U2 48 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD MAR PY 2013 VL 48 IS 3 BP 315 EP 321 DI 10.1007/s00535-013-0777-2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 122FZ UT WOS:000317305000003 PM 23475322 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Hermann Staudinger-Founder of Polymer Chemistry SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 NR 1 TC 0 Z9 0 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2013 VL 88 IS 3 BP E23 EP E23 DI 10.1016/j.mayocp.2012.01.026 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 122QD UT WOS:000317331800001 ER PT J AU Maeder, ML Linder, SJ Reyon, D Angstman, JF Fu, YF Sander, JD Joung, JK AF Maeder, Morgan L. Linder, Samantha J. Reyon, Deepak Angstman, James F. Fu, Yanfang Sander, Jeffry D. Joung, J. Keith TI Robust, synergistic regulation of human gene expression using TALE activators SO NATURE METHODS LA English DT Article ID TRANSCRIPTION; PROTEINS; EFFECTORS; CELLS; RNAI AB Artificial activators designed using transcription activator like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins. C1 [Maeder, Morgan L.; Linder, Samantha J.; Reyon, Deepak; Angstman, James F.; Fu, Yanfang; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Maeder, Morgan L.; Linder, Samantha J.; Reyon, Deepak; Angstman, James F.; Fu, Yanfang; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Linder, Samantha J.; Reyon, Deepak; Angstman, James F.; Fu, Yanfang; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Reyon, Deepak; Fu, Yanfang; Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM jjoung@partners.org FU US National Institutes of Health (NIH) [DP1 OD006862, NIH P50 HG005550, R01 NS073124]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award; US National Science Foundation Graduate Research Fellowship; NIH [T32 CA009216, P30 NS45776] FX This work was supported by a US National Institutes of Health (NIH) Director's Pioneer Award DP1 OD006862 (J.K.J.), NIH P50 HG005550 and R01 NS073124 (J.K.J.), the Jim and Ann Orr Massachusetts General Hospital Research Scholar Award (J.K.J.), a US National Science Foundation Graduate Research Fellowship (M.L.M.), and NIH T32 CA009216 (J.D.S.). We thank J. Foley for technical assistance with construction of TALE-activator plasmids, R. Mylvaganam for technical assistance with flow cytometry, and the Massachusetts General Hospital Nucleic Acid Quantitation Core (supported by NIH P30 NS45776) for assistance with performing real-time reverse-transcription-PCR assays. NR 20 TC 95 Z9 98 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD MAR PY 2013 VL 10 IS 3 BP 243 EP 245 DI 10.1038/NMETH.2366 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 113FB UT WOS:000316650800020 PM 23396285 ER PT J AU Mandal, PK Rossi, DJ AF Mandal, Pankaj K. Rossi, Derrick J. TI Reprogramming human fibroblasts to pluripotency using modified mRNA SO NATURE PROTOCOLS LA English DT Article ID HUMAN IPS CELLS; STEM-CELLS; SENDAI-VIRUS; RIG-I; GENERATION; VECTOR; PSEUDOURIDINE; INTEGRATION; EXPRESSION; INDUCTION AB Induced pluripotent stem (iPS) cells hold the potential to revolutionize regenerative medicine through their capacity to generate cells of diverse lineages for future patient-specific cell-based therapies. To facilitate the transition of iPS cells to clinical practice, a variety of technologies have been developed for transgene-free pluripotency reprogramming. We recently reported efficient iPS cell generation from human fibroblasts using synthetic modified mRNAs. Here we describe a stepwise protocol for the generation of modified mRNA-derived iPS cells from primary human fibroblasts, focusing on the critical parameters including medium choice, quality control, and optimization steps needed for synthesizing modified mRNAs encoding reprogramming factors and introducing these into cells over the course of 2-3 weeks to ensure successful reprogramming. The protocol described herein is for reprogramming of human fibroblasts to pluripotency; however, the properties of modified mRNA make it a powerful platform for protein expression, which has broad applicability in directed differentiation, cell fate specification and therapeutic applications. C1 [Mandal, Pankaj K.; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Mandal, Pankaj K.; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Rossi, Derrick J.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Rossi, DJ (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM derrick.rossi@childrens.harvard.edu RI mandal, pankaj/B-4885-2016 FU Harvard Stem Cell Institute FX We thank T. Schlaeger, L. Daheron, W. Ebina and L. Zhangi for their valuable suggestions and discussion, and L. Warren and P. Manos for past contributions. We thank A. Ettenger for technical assistance. This work was funded in part by a grant from the Harvard Stem Cell Institute. D.J.R. is a New York Stem Cell Foundation Robertson Investigator. NR 35 TC 66 Z9 69 U1 6 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD MAR PY 2013 VL 8 IS 3 BP 568 EP 582 DI 10.1038/nprot.2013.019 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 119PU UT WOS:000317110600011 PM 23429718 ER PT J AU Zima, BT Murphy, JM Scholle, SH Hoagwood, KE Sachdeva, RC Mangione-Smith, R Woods, D Kamin, HS Jellinek, M AF Zima, Bonnie T. Murphy, J. Michael Scholle, Sarah Hudson Hoagwood, Kimberly Eaton Sachdeva, Ramesh C. Mangione-Smith, Rita Woods, Donna Kamin, Hayley S. Jellinek, Michael TI National Quality Measures for Child Mental Health Care: Background, Progress, and Next Steps SO PEDIATRICS LA English DT Article DE ADHD; child mental health; clinical validity; depression; quality improvement research; quality measures ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PEDIATRIC PRACTICE; SETTINGS; MEDICAID; CHIPRA; HYPERACTIVITY; ADOLESCENTS; PERSPECTIVE; PREVENTION; DEPRESSION AB OBJECTIVE: To review recent health policies related to measuring child health care quality, the selection processes of national child health quality measures, the nationally recommended quality measures for child mental health care and their evidence strength, the progress made toward developing new measures, and early lessons learned from these national efforts. METHODS: Methods used included description of the selection process of child health care quality measures from 2 independent national initiatives, the recommended quality measures for child mental health care, and the strength of scientific evidence supporting them. RESULTS: Of the child health quality measures recommended or endorsed during these national initiatives, only 9 unique measures were related to child mental health. CONCLUSIONS: The development of new child mental health quality measures poses methodologic challenges that will require a paradigm shift to align research with its accelerated pace. Pediatrics 2013; 131:S38-S49 C1 [Zima, Bonnie T.] Univ Calif Los Angeles, Ctr Hlth Serv & Soc, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Murphy, J. Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Scholle, Sarah Hudson] Natl Comm Qual Assurance, Washington, DC USA. [Hoagwood, Kimberly Eaton] NYU, Med Ctr, Dept Child Psychiat, New York, NY 10016 USA. [Sachdeva, Ramesh C.] Med Coll Wisconsin, Childrens Hosp, Milwaukee, WI 53226 USA. [Mangione-Smith, Rita] Univ Washington, Seattle Childrens Res Inst, Ctr Child Hlth Behav & Dev, Seattle, WA 98195 USA. [Woods, Donna] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA. [Kamin, Hayley S.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Jellinek, Michael] Harvard Univ, Sch Med, Partners Healthcare, Boston, MA USA. RP Zima, BT (reprint author), Univ Calif Los Angeles, Ctr Hlth Serv & Soc, 10920 Wilshire Blvd,300, Los Angeles, CA 90024 USA. EM bzima@mednet.ucla.edu FU National Institute of Mental Health [P30 MH082760]; Agency for Healthcare Research and Quality [1U18HS020506, U18 HS020503, 1U18HS020498]; National Institutes of Health FX This study was supported by the National Institute of Mental Health (P30 MH082760), the Agency for Healthcare Research and Quality (1U18HS020506, U18 HS020503, 1U18HS020498). Funded by the National Institutes of Health. NR 59 TC 20 Z9 20 U1 0 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2013 VL 131 SU 1 BP S38 EP S49 DI 10.1542/peds.2012-1427e PG 12 WC Pediatrics SC Pediatrics GA 121UK UT WOS:000317269700004 PM 23457148 ER PT J AU Rice, T Dobry, Y Wang, E Novakovic, V Sher, L AF Rice, Timothy Dobry, Yuriy Wang, Eugene Novakovic, Vladan Sher, Leo TI Cognitive effects of quetiapine in a patient with dementia with Lewy bodies SO PSYCHOGERIATRICS LA English DT Article DE atypical antipsychotics; CATIE-AD; cognition; dementia with Lewy bodies; neurodegenerative disorders; quetiapine ID VISUAL HALLUCINATIONS; NEUROLEPTIC SENSITIVITY; ALZHEIMERS-DISEASE; BODY DEMENTIA; SCHIZOPHRENIA; METAANALYSIS; OLANZAPINE; PSYCHOSIS; SYMPTOMS; EFFICACY AB A recent large-scale randomized controlled clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study, found a significant worsening of cognitive functioning in a sample of patients with Alzheimer's disease. To date there have been no equally powered studies examining the cognitive effects of atypical antipsychotics in patients with dementia with Lewy bodies, the second most prevalent neurodegenerative disorder. This case report describes a significant cognitive improvement observed through the use of an atypical antipsychotic in a patient with dementia with Lewy bodies. The observed divergence in cognitive responsiveness is discussed mechanistically on both the clinical and neuromolecular level. Limitations to this case study design are presented and discussed. The prudence of caution in importing the results of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study to the dementia with Lewy bodies population is summarized and presented for psychiatrists, neurologists and primary care providers, with an intent to stimulate discussion and further research. C1 [Rice, Timothy; Dobry, Yuriy; Wang, Eugene; Novakovic, Vladan; Sher, Leo] Mt Sinai Sch Med, New York, NY 10029 USA. [Rice, Timothy; Dobry, Yuriy; Novakovic, Vladan; Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY USA. RP Rice, T (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1425 Madison Ave,Box 1230, New York, NY 10029 USA. EM timothy.rice@mssm.edu NR 33 TC 1 Z9 1 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1346-3500 J9 PSYCHOGERIATRICS JI Psychogeriatrics PD MAR PY 2013 VL 13 IS 1 BP 52 EP 57 DI 10.1111/j.1479-8301.2012.00414.x PG 6 WC Geriatrics & Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 117QG UT WOS:000316967600009 PM 23551413 ER PT J AU Czuczman, AD Thomas, LE Boulanger, AB Peak, DA Senecal, EL Brown, DF Marill, KA AF Czuczman, Amanda D. Thomas, Lisa E. Boulanger, Alyson B. Peak, David A. Senecal, Emily L. Brown, David F. Marill, Keith A. TI Interpreting Red Blood Cells in Lumbar Puncture: Distinguishing True Subarachnoid Hemorrhage From Traumatic Tap SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY; EMERGENCY-DEPARTMENT; MANAGEMENT; DIAGNOSIS; SENSITIVITY; HEADACHE; ANEURYSM; RATIO; SCAN; RULE AB Objectives: The study purpose was to determine the optimal use of lumbar puncture (LP) red blood cell (RBC) counts to identify subarachnoid hemorrhage (SAH) when some blood remains in the final tube. Methods A case series was performed at a tertiary emergency department (ED). Records of 4,496 consecutive adult patients billed for LPs between 2001 and 2009 were reviewed. Inclusion criteria were headache (HA), final tube RBCs5, and neurovascular imaging within 2weeks of the visit. Demographics, relevant history and physical examination components, LP results, and neuroimaging findings were recorded for 280 patients. True-positive (TP) and true-negative (TN) SAH were strictly defined. Primary outcomes were the areas under the receiver operating characteristic curves (AUC) for final tube RBC count, differential RBC count between the final and initial tubes, and absolute differential RBC count between the final and initial tubes divided by the mean RBC count of the two tubes (also called the percent change in RBC count). Results There were 26 TP and 196 TN results; 58 patients were neither. The TP group consisted of 19 patients with visible or possible SAH on imaging (17 on noncontrast head computed tomography [CT; 12 definite and five possible] and two on magnetic resonance imaging), six with xanthochromia and a vascular lesion (aneurysm or arteriovenous malformation [AVM]>2mm), and one with xanthochromia and polymerase chain reaction (PCR)-positive meningitis. As a test for SAH, final tube RBC AUC was 0.85 (95% confidence interval [CI]=0.80 to 0.91). Interval likelihood ratios (LRs) for final tube RBC count were LR 0 (95% CI=0 to 0.3) for RBCs<100, LR 1.6 (95% CI=1.1 to 2.3) for 10010,000. Differential RBC count was not associated with SAH, with AUC 0.45 (95% CI=0.31 to 0.60). However, the percent change in RBC count between the final and initial tubes had an AUC 0.84 (95% CI=0.78 to 0.90), and the optimal test threshold for SAH was 0.63, with positive LR 3.6 (95% CI=2.7 to 4.7) and negative LR 0.10 (95% CI=0.03 to 0.4) for percent change<63% and>63%, respectively. This test added additional independent information to the final tube RBC count based on improved logistic regression model fit and discriminatory ability as measured by the LR test and cstatistic, respectively. Conclusions Final LP tube RBC count and the percent change in RBC count, but not the simple differential count between the final and initial tubes, were associated with SAH. In this sample, there were no patients with SAH who had RBCs<100 in the final tube, and RBCs>10,000 increased the odds of SAH by a factor of 6. ACADEMIC EMERGENCY MEDICINE 2013; 20:247-256 (C) 2013 by the Society for Academic Emergency Medicine C1 [Czuczman, Amanda D.] Beverly Hosp, Dept Emergency Med, Beverly, MA USA. [Thomas, Lisa E.] Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA USA. [Boulanger, Alyson B.; Peak, David A.; Senecal, Emily L.; Brown, David F.; Marill, Keith A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Czuczman, AD (reprint author), Beverly Hosp, Dept Emergency Med, Beverly, MA USA. EM amandaczuczman@gmail.com NR 21 TC 14 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2013 VL 20 IS 3 BP 247 EP 256 DI 10.1111/acem.12095 PG 10 WC Emergency Medicine SC Emergency Medicine GA 112VZ UT WOS:000316623600005 PM 23517256 ER PT J AU Diercks, DB Mumma, BE Peacock, WF Hollander, JE Safdar, B Mahler, SA Miller, CD Counselman, FL Birkhahn, R Schrock, J Singer, AJ Nagurney, JT AF Diercks, Deborah B. Mumma, Bryn E. Peacock, W. Frank Hollander, Judd E. Safdar, Basmah Mahler, Simon A. Miller, Chadwick D. Counselman, Francis L. Birkhahn, Robert Schrock, Jon Singer, Adam J. Nagurney, John T. TI Incremental Value of Objective Cardiac Testing in Addition to Physician Impression and Serial Contemporary Troponin Measurements in Women SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; DIAGNOSTIC-ACCURACY; PREDICTIVE ABILITY; CHEST-PAIN; ROC CURVE; I ASSAY; EMERGENCY; RECLASSIFICATION AB Objectives: Guidelines recommend that patients presenting to the emergency department (ED) with chest pain who are at low risk for acute coronary syndrome (ACS) receive an objective cardiac evaluation with a stress test or coronary imaging. It is uncertain whether all women derive benefit from this process. The study aim was to determine the incremental value of objective cardiac testing after serial cardiac markers and physician risk assessment. Methods Women enrolled in the 18-site Myeloperoxidase in the Diagnosis of Acute Coronary Syndrome (MIDAS) study had serial troponinI measured at time 0 and 90minutes and physician risk assessment for the presence of ACS. Risk estimates obtained at the time of ED evaluation were dichotomized as high or nonhigh risk. The primary outcome was the composite of acute myocardial infarction (AMI) or revascularization at 30days. Logistic regression with receiver operator characteristic (ROC) curves and net reclassification index were used to determine the diagnostic accuracy for the composite outcome of 30-day MI or revascularization for two models: 1) troponinI results and physician risk assessment alone and 2) troponinI results, physician risk assessment, and objective cardiac testing. Results A total of 460 women with a median age 58years (interquartile range [IQR]=48.5 to 68years) were included, and 32 (6.9%) experienced AMI or revascularization by 30days. Comparison of the area under the ROC curves (AUC) showed that the addition of objective cardiac testing to the combination of troponinI results and physician risk assessment did not significantly improve prediction of 30-day AMI or revascularization (AUC=0.85 vs. 0.89; p=0.053). Using a threshold of 1%, net reclassification index showed that the addition of objective cardiac testing to troponinI results and physician risk assessment worsened the prediction for 30-day AMI and revascularization. All of the reclassified patients were false positives, with nine (2.1%) patients incorrectly reclassified from <1% risk to 1% risk of 30-day AMI or revascularization. Conclusions In the era of contemporary troponin assays, objective cardiac testing after an ED clinician risk assessment of nonhigh risk and negative troponinI results at 0 and 90minutes does not improve the prediction of 30-day AMI or revascularization in women presenting with chest pain or other symptoms of cardiac ischemia. ACADEMIC EMERGENCY MEDICINE 2013; 20:265-270 (C) 2013 by the Society for Academic Emergency Medicine C1 [Diercks, Deborah B.; Mumma, Bryn E.] Univ Calif Davis, Dept Emergency Med, Sacramento, CA 95817 USA. [Peacock, W. Frank] Cleveland Clin, Dept Emergency Med, Cleveland, OH 44106 USA. [Hollander, Judd E.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Safdar, Basmah] Yale Univ, Dept Emergency Med, New Haven, CT USA. [Mahler, Simon A.; Miller, Chadwick D.] Wake Forest Univ Hlth Sci, Dept Emergency Med, Winston Salem, NC USA. [Counselman, Francis L.] Eastern Virginia Med Sch, Dept Emergency Med, Norfolk, VA 23501 USA. [Birkhahn, Robert] New York Methodist Hosp, Dept Emergency Med, New York, NY USA. [Schrock, Jon] Metrohlth Med Ctr, Div Emergency Med, Cleveland, OH USA. [Singer, Adam J.] SUNY Stony Brook, Dept Emergency Med, Stony Brook, NY 11794 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Diercks, DB (reprint author), Univ Calif Davis, Dept Emergency Med, Sacramento, CA 95817 USA. EM dbdiercks@ucdavis.edu OI Hollander, Judd/0000-0002-1318-2785 FU Alere FX The MIDAS trial was supported by a research grant from Alere. NR 24 TC 2 Z9 2 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2013 VL 20 IS 3 BP 265 EP 270 DI 10.1111/acem.12092 PG 6 WC Emergency Medicine SC Emergency Medicine GA 112VZ UT WOS:000316623600007 PM 23517258 ER PT J AU Cho, HS Alcantara, D Yuan, HS Sheth, RA Chen, HH Huang, P Andersson, SB Sosnovik, DE Mahmood, U Josephson, L AF Cho, Hoonsung Alcantara, David Yuan, Hushan Sheth, Rahul A. Chen, Howard H. Huang, Peng Andersson, Sean B. Sosnovik, David E. Mahmood, Umar Josephson, Lee TI Fluorochrome-Functionalized Nanoparticles for Imaging DNA in Biological Systems SO ACS NANO LA English DT Article DE DNA; Imaging; nanoparticle; fluorochrome; biosensing ID THIAZOLE ORANGE; CELL-DEATH; MAGNETIC NANOPARTICLES; MOLECULAR-INTERACTIONS; DRUG CARRIERS; INTERCALATION; BINDING; DISTRIBUTIONS; ACCUMULATION; PURIFICATION AB Attaching DNA binding fluorochromes to nanoparticles (NPs) provides a way of obtaining NPs that bind to DNA through fluorochrome mediated Interactions. To obtain a nanoparticle (NP) that bound to the DNA in biological systems, we attached the DNA binding fluorochrome, TO-PRO 1(TO), to the surface of the Feraheme (FH) NP, to obtain a fluorochrome-functionalized NP denoted TO-FH. When reacted with DNA in vitro, TO-FH formed microaggregates that were characterized by fluorescence, light scattering, and T2 changes. The formation of DNA/TO-FH microaggregates was also characterized by AFM, with microaggregates exhibiting a median size of 200 nm, and consisting of DNA and multiple TO-FH NPs whose individual diameters were only 25-35 nm. TO-FH failed to bind normal cells In culture, but treatment with chemotherapeutic agents or detergents yielded necrotic cells that bound TO-FH and vital fluorochromes similarly. The uptake of TO-FH by HT-29 xenografts (treated with 5-FU and oxaliplatin) was evident by surface fluorescence and MRI. Attaching multiple DNA binding fluorochromes to magnetic nanoparticles provides a way of generating DNA binding NPs that can be used to detect DNA detection by microaggregate formation in vitro, for imaging the DNA of necrotic cells In culture, and for imaging the DNA of a tumor treated with a chemotherapeutic agent. Fluorochrome functionalized NPs are a multimodal (magnetic and fluorescent), highly multivalent (n approximate to 10 fluorochromes/NP) nanomaterials useful for imaging the DNA of biological systems. C1 [Cho, Hoonsung; Yuan, Hushan; Mahmood, Umar; Josephson, Lee] Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA. [Sheth, Rahul A.; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Charlestown, MA 02129 USA. [Chen, Howard H.; Sosnovik, David E.; Josephson, Lee] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Alcantara, David] Univ Zaragoza, Inst Nanociencia Aragon, E-50009 Zaragoza, Spain. [Huang, Peng; Andersson, Sean B.] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. [Andersson, Sean B.] Boston Univ, Div Syst Engn, Boston, MA 02215 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA. EM ljosephson@mgh.harvard.edu RI Andersson, Sean/A-5903-2010; Alcantara, David /A-3357-2014 FU NIBIB NIH HHS [R01 EB009691, R01 EB011996] NR 36 TC 14 Z9 14 U1 2 U2 66 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD MAR PY 2013 VL 7 IS 3 BP 2032 EP 2041 DI 10.1021/nn305962n PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 115YB UT WOS:000316846700019 PM 23373524 ER PT J AU Lawrence, AE Taft, CT AF Lawrence, Amy E. Taft, Casey T. TI Shame, posttraumatic stress disorder, and intimate partner violence perpetration SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article ID COGNITIVE PROCESSING THERAPY; ARTICULATED THOUGHTS; YOUNG ADOLESCENTS; ANGER; VICTIMS; GUILT; VETERANS; PTSD; MALTREATMENT; AGGRESSION AB Drawing from theoretical and empirical literature linking shame to aggression and violence, the authors propose that shame may be an important variable to examine in studies of posttraumatic stress disorder (PTSD) and intimate partner violence (IPV) perpetration. The authors review the literature linking shame, PTSD, and IPV, propose ideas for future research, and suggest that shame and shame regulation may be a useful target of clinical interventions aimed at violence perpetrators. (C) 2012 Published by Elsevier Ltd. C1 [Lawrence, Amy E.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Taft, Casey T.] Natl Ctr PTSD, Washington, DC USA. [Taft, Casey T.] Boston Univ, Boston, MA 02215 USA. RP Lawrence, AE (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM alawrenc@bu.edu NR 46 TC 8 Z9 8 U1 3 U2 33 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD MAR-APR PY 2013 VL 18 IS 2 BP 191 EP 194 DI 10.1016/j.avb2012.10.002 PG 4 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA 110IY UT WOS:000316437000001 ER PT J AU Kugel, S Mostoslavsky, R AF Kugel, Sita Mostoslavsky, Raul TI SIRT1 Activators: The Evidence STACks up SO AGING-US LA English DT Editorial Material ID SMALL-MOLECULE ACTIVATORS; RESVERATROL; SIRTUINS; SURVIVAL; SRT1720; BIOLOGY; MICE C1 [Kugel, Sita; Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Kugel, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu NR 10 TC 6 Z9 6 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD MAR PY 2013 VL 5 IS 3 BP 142 EP 143 PG 2 WC Cell Biology SC Cell Biology GA 116DO UT WOS:000316863000001 PM 23474671 ER PT J AU Tobin, MJ AF Tobin, M. J. TI Hypercapnia: keeping therapy and diagnosis distinct SO ANAESTHESIA AND INTENSIVE CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; DEAD SPACE; VENTILATION; MORTALITY; VOLUME C1 [Tobin, M. J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Tobin, M. J.] Loyola Univ Chicago, Stritch Sch Med, Hines, IL USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AUSTRALIAN SOC ANAESTHETISTS PI EDGECLIFF PA P O BOX 600, EDGECLIFF, NSW 2027, AUSTRALIA SN 0310-057X J9 ANAESTH INTENS CARE JI Anaesth. Intensive Care PD MAR PY 2013 VL 41 IS 2 BP 149 EP 150 PG 2 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 115TP UT WOS:000316835100002 PM 23577370 ER PT J AU Allard, C Doyon, M Brown, C Carpentier, AC Langlois, MF Hivert, MF AF Allard, Catherine Doyon, Myriam Brown, Christine Carpentier, Andre C. Langlois, Marie-France Hivert, Marie-France TI Lower leptin levels are associated with higher risk of weight gain over 2 years in healthy young adults SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE NUTRITION ET METABOLISME LA English DT Article DE adipokine; leptin; weight regulation; adiposity; physiology; young adults; university students; energy expenditure; dietary intake; prospective study ID SERUM LEPTIN; FITNESS TEST; OBESE WOMEN; HUMANS; GENE; FAT AB Complete leptin deficiency is associated with weight gain and extreme obesity, according to studies of animals and of monogenic obesity in humans. It is still a matter of debate whether relative leptin deficiency plays a physiologic role in adiposity regulation in free-living humans. We hypothesized that leptin levels would be associated with subsequent weight changes in healthy normal-weight young adults. Our prospective cohort involved 150 healthy young adults (114 women and 36 men) followed over their years of study at the Universite de Sherbrooke. Anthropometric measurements, fasting blood samples, 3-day food diaries, and a physical activity questionnaire were collected at baseline. Leptin levels were measured with radioimmunoassay. Associations between baseline leptin levels and subsequent anthropometric changes were assessed with multivariable linear regression models to account for adiposity at baseline, food intake, and energy expenditure. Over the 2-year follow-up, changes in body mass index (BMI) ranged from -0.8 to +2.6 kg.m(-2) in men (mean BMI change, +0.6 kg.m(-2)) and from -2.5 to +3.7 kg.m(-2) in women (mean BMI change, +0.1 kg.m(-2)). Lower leptin levels at baseline were associated with a higher risk of weight gain in women (r = -0.24; p = 0.01 for change in BMI) and in men (r = -0.27, p = 0.11), even after accounting for baseline BMI, total daily caloric intake, and energy expenditure (p = 0.02). In the subsample measured at 4 years (n = 63), baseline leptin levels were not associated with 4-year weight changes. Lower leptin levels are associated with a higher risk of weight gain over 2 years in healthy young adults. C1 [Allard, Catherine; Doyon, Myriam; Brown, Christine; Carpentier, Andre C.; Langlois, Marie-France; Hivert, Marie-France] Univ Sherbrooke, Dept Med, Ctr Rech Clin Etienne Le Bel, Sherbrooke, PQ J1H 5N4, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Univ Sherbrooke, Dept Med, Ctr Rech Clin Etienne Le Bel, Sherbrooke, PQ J1H 5N4, Canada. EM marie-france.hivert@usherbrooke.ca FU Canadian Diabetes Association (CDA); Danone Institute; Fonds de la recherche en sante du Quebec (FRSQ) FX This work was supported by grants from the Canadian Diabetes Association (CDA) and the Danone Institute. The Centre de recherche clinique Etienne-Le Bel is a Fonds de la recherche en sante du Quebec (FRSQ)-funded research center. M. F. H. received career awards from the FRSQ (Research Scholar Award, junior 1 level) and from the CDA (Clinical Scientist). M. F. L. is the recipient of a career award from the FRSQ (National researcher). A. C. C. is the recipient of the CIHR-GSK Chair in Diabetes and is supported by a career award from the FRSQ (Research Scholar Award, senior level). NR 29 TC 4 Z9 4 U1 0 U2 6 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 1200 MONTREAL ROAD, BUILDING M-55, OTTAWA, ON K1A 0R6, CANADA SN 1715-5312 J9 APPL PHYSIOL NUTR ME JI Appl. Physiol. Nutr. Metab. PD MAR PY 2013 VL 38 IS 3 BP 280 EP 285 DI 10.1139/apnm-2012-0225 PG 6 WC Nutrition & Dietetics; Physiology; Sport Sciences SC Nutrition & Dietetics; Physiology; Sport Sciences GA 116CP UT WOS:000316860500008 PM 23537019 ER PT J AU Blum, MA Singh, JA Lee, GC Richardson, D Chen, W Ibrahim, SA AF Blum, Marissa A. Singh, Jasvinder A. Lee, Gwo-Chin Richardson, Diane Chen, Wei Ibrahim, Said A. TI Patient Race and Surgical Outcomes After Total Knee Arthroplasty: An Analysis of a Large Regional Database SO ARTHRITIS CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; MYOCARDIAL-INFARCTION MORTALITY; JOINT REPLACEMENT SURGERY; TOTAL HIP; AFRICAN-AMERICAN; THE-LITERATURE; UNITED-STATES; RIGHT TOOL; APR-DRGS; RISK AB Objective. To examine racial differences in surgical complications, mortality, and revision rates after total knee arthroplasty. Methods. We studied patients undergoing primary total knee arthroplasty using 2001-2007 Pennsylvania Health Care Cost Containment Council data. We conducted bivariate analyses to assess the risk of complications such as myocardial infarction, venous thromboembolism, wound infections, and failure of prosthesis, as well as 30-day and 1-year overall mortality after elective total knee arthroplasty, between racial groups. We estimated Kaplan-Meier 1- and 5-year surgical revision rates, and fit multivariable Cox proportional hazards models to compare surgical revision by race, incorporating 5 years of followup. We adjusted for patient age, sex, length of hospital stay, surgical risk of death, type of health insurance, hospital surgical volume, and hospital teaching status. Results. In unadjusted analyses, there were no significant differences by racial group for either overall 30-day or in-hospital complication rates, or 30-day and 1-year mortality rates. Adjusted Cox models incorporating 5 years of followup showed an increased risk of revisions for African American patients (hazard ratio [HR] 1.39, 95% confidence interval [95% CI] 1.08-1.80), younger patients (HR 2.30, 95% CI 1.96-2.69), and lower risk for female patients (HR 0.81, 95% CI 0.71-0.92). Conclusion. In this sample of patients who underwent knee arthroplasty, we found no significant racial differences in major complication rates or mortality. However, African American patients, younger patients, and male patients all had significantly higher rates of revision based on 5 years of followup. C1 [Blum, Marissa A.] Temple Univ, Sch Med, Philadelphia, PA USA. [Singh, Jasvinder A.] VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Rochester, MN USA. [Lee, Gwo-Chin; Ibrahim, Said A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Richardson, Diane; Chen, Wei; Ibrahim, Said A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Blum, MA (reprint author), 3322 North Broad St,Suite 205, Philadelphia, PA 19140 USA. EM Marissa.blum@tuhs.temple.edu OI singh, jasvinder/0000-0003-3485-0006 FU NIH [1-KL2-RR-024151-01]; NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [1-K24-AR-055259-06]; Zimmer and Smith Nephew FX Dr. Singh's work was supported by the NIH (Clinical Translational Science Award 1-KL2-RR-024151-01). Dr. Ibrahim's work was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 1-K24-AR-055259-06). Dr. Lee's work was supported by Zimmer and Smith & Nephew. NR 34 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAR PY 2013 VL 65 IS 3 BP 414 EP 420 DI 10.1002/acr.21834 PG 7 WC Rheumatology SC Rheumatology GA 116UE UT WOS:000316907700010 PM 22933341 ER PT J AU Ay, I Ay, H AF Ay, Ilknur Ay, Hakan TI Ablation of the sphenopalatine ganglion does not attenuate the infarct reducing effect of vagus nerve stimulation SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Article DE Cerebral ischemia; Vagus nerve; Sphenopalatine ganglion; Cerebral blood flow; Electrical stimulation; Rat ID MIDDLE CEREBRAL-ARTERY; BRAIN-STEM PROJECTIONS; BLOOD-FLOW; ELECTRICAL-STIMULATION; MOTOR COMPONENTS; RAT; OCCLUSION; PATHWAYS; ISCHEMIA; NEURONS AB Electrical stimulation of the cervical vagus nerve reduces infarct size by approximately 50% after cerebral ischemia in rats. The mechanism of ischemic protection by vagus nerve stimulation (VNS) is not known. In this study, we investigated whether the infarct reducing effect of VNS was mediated by activation of the parasympathetic vasodilator fibers that originate from the sphenopalatine ganglion (SPG) and innervate the anterior cerebral circulation. We examined the effects of electrical stimulation of the cervical vagus nerve in two groups of rats: one with and one without SPG ablation. Electrical stimulation was initiated 30 min after induction of ischemia, and lasted for 1 h. Measurement of infarct size 24 h later revealed that the volume of ischemic damage was smaller in those animals that received VNS treatment (41.32 +/- 2.07% vs. 24.19 +/- 2.62% of the contralateral hemispheric volume, n = 6 in both; p<0.05). SPG ablation did not abolish this effect; the reduction in infarct volume following VNS was 58% in SPG-damaged animals, 41% in SPG-intact animals (p> 0.05). In both SPG-intact and SPG-damaged animals VNS treatment resulted in better motor outcome (p<0.05 vs. corresponding controls for both). Our findings show that VNS can protect the brain against acute ischemic injury, and that this effect is not mediated by SPG projections. (C) 2012 Elsevier B.V. All rights reserved. C1 [Ay, Ilknur; Ay, Hakan] Massachusetts Gen Hosp East, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Dept Radiol, Charlestown, MA 02129 USA. RP Ay, I (reprint author), Massachusetts Gen Hosp East, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM iay@partners.org FU American Heart Association [10SDG2600218]; NIH-NINDS [RO1NS059710]; Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital; Center for Functional Neuroimaging Technologies [P41RR14075, a P41]; Biomedical Technology Program of the National Center for Research Resources (NCRR); National Institutes of Health FX I.A. was supported by the American Heart Association (10SDG2600218). HA. was supported by NIH-NINDS (RO1NS059710). This research was carried out in whole at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. We thank Sinan Ozer for his help with data analysis and Nichole L Eusemann for proofreading the manuscript. NR 36 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD MAR PY 2013 VL 174 IS 1-2 BP 31 EP 35 DI 10.1016/j.autneu.2012.12.001 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 115UJ UT WOS:000316837100006 PM 23273773 ER PT J AU Deutsch, CK Hreczko, T Holmes, LB AF Deutsch, Curtis K. Hreczko, Tania Holmes, Lewis B. TI Quantitative assessment of craniofacial morphology in Johanson-Blizzard syndrome SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE Johanson-Blizzard syndrome; autosomal recessive; UBR1 mutations; anthropometry; craniofacial dysmorphology ID PRENATAL ULTRASONOGRAPHIC DIAGNOSIS; UBR1; DELINEATION AB BACKGROUND Here we apply objective, reliable methods of dysmorphology diagnosis to a patient with JohansonBlizzard syndrome (MIM #243800). Using an extensive normative database, we computed standardized scores on a graded continuum for operational definitions of nasal alar hypoplasia, a commonly observed feature of this condition. CASE Most of these measurements in this case were greater than 2 standard deviations below the mean, adjusted for age, gender, and ethnicity. CONCLUSION This report provides a worked example of quantitative anthropometric assessment in the context of a case report, using tools that may find general application in clinical genetics. Birth Defects Research (Part A), 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Deutsch, Curtis K.] Eunice Kennedy Shriver Ctr Mental Retardat Inc, UMMS, Waltham, MA 02452 USA. [Deutsch, Curtis K.; Holmes, Lewis B.] Harvard Univ, Sch Med, Boston, MA USA. [Hreczko, Tania] Hosp Sick Children, Craniofacial Ctr, Toronto, ON, Canada. [Holmes, Lewis B.] MassGen Hosp Children, Genet Unit, Serv Pediat, Boston, MA USA. RP Deutsch, CK (reprint author), Eunice Kennedy Shriver Ctr Mental Retardat Inc, 200 Trapelo Rd, Waltham, MA 02452 USA. EM cdeutsch@shriver.org FU Peabody Foundation (Boston, MA); NIH [NICHD P30 HD004147] FX Supported by the grants from the Peabody Foundation (Boston, MA) and NIH (NICHD P30 HD004147). NR 29 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAR PY 2013 VL 97 IS 3 BP 166 EP 169 DI 10.1002/bdra.23121 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 113VE UT WOS:000316696600006 PM 23463671 ER PT J AU Greenberg, JL Falkenstein, M Reuman, L Fama, J Marques, L Wilhelm, S AF Greenberg, Jennifer L. Falkenstein, Martha Reuman, Lillian Fama, Jeanne Marques, Luana Wilhelm, Sabine TI The phenomenology of self-reported body dysmorphic disorder by proxy SO BODY IMAGE LA English DT Article DE Body dysmorphic disorder; Body dysmorphic disorder by proxy; Dysmorphophobia; Obsessive compulsive spectrum; BDD ID QUALITY-OF-LIFE; POPULATION; IMPAIRMENT; PREVALENCE; IMPACT; SCALE AB Body dysmorphic disorder by proxy (BDDBP), a preoccupation with a perceived defect in another person's appearance may represent a variant of BDD. However, BDDBP has received little empirical attention. We present here the phenomenology of 11 individuals with self-reported BDDBP. Participants completed an internet-based survey that assessed symptoms, psychosocial impact, and treatment history. Participants (8 females, 3 males) reported preoccupation with a wide array of individuals (e.g., spouse, stranger). Body parts of concern most commonly involved the face and head. Most participants spent several (e.g., 3-8) hours per day preoccupied by perceived defects in the person of concern (POC). All participants engaged in rituals to try to alleviate distress or improve the POC's appearance. Most avoided social/occupational activities, including contact with the POC. The impact of BDDBP was profound, particularly on relationships. Findings may help elucidate diagnostic criteria, course, and treatment. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Greenberg, Jennifer L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, JL (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM jlgreenberg@partners.org OI Falkenstein, Martha/0000-0001-5074-3409 FU NIMH NIH HHS [K23 MH096029] NR 22 TC 7 Z9 7 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 J9 BODY IMAGE JI Body Image PD MAR PY 2013 VL 10 IS 2 BP 243 EP 246 DI 10.1016/j.bodyim.2013.01.001 PG 4 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA 118LM UT WOS:000317027000012 PM 23384683 ER PT J AU Blashill, AJ AF Blashill, Aaron J. TI Psychosocial correlates of frequent indoor tanning among adolescent boys SO BODY IMAGE LA English DT Article DE Indoor tanning; Steroids; Eating pathology; Victimization; Adolescent boys; Skin cancer ID UNITED-STATES; SKIN-CANCER; APPEARANCE; BEHAVIORS; MOTIVES; GENDER AB The aim of the current study was to assess psychosocial correlates (i.e., perceived weight, weight control strategies, substance use, and victimization) of frequent indoor tanning in adolescent boys a group at high risk for developing skin cancer. Participants (N=7,907) were drawn from a nationally representative sample of adolescent boys attending high school in the United States. Binary logistic regression revealed that extreme weight control strategies, particularly steroid use (odds ratio=3.67) and compensatory vomiting (odds ratio=2.34), along with substance use and victimization, were significantly related to frequent indoor tanning. These results highlight the role of appearance-changing, and health-risk behaviors in the context of frequent indoor tanning. Skin cancer prevention interventions may benefit from adopting approaches that integrate the treatment of body dissatisfaction and subsequent maladaptive behaviors. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Blashill, Aaron J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU NIMH NIH HHS [K23 MH096647, K23MH096647] NR 22 TC 9 Z9 9 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 J9 BODY IMAGE JI Body Image PD MAR PY 2013 VL 10 IS 2 BP 259 EP 262 DI 10.1016/j.bodyim.2012.11.005 PG 4 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA 118LM UT WOS:000317027000016 PM 23276832 ER PT J AU Johnson, KA Baig, M Ramsey, D Lisanby, SH Avery, D McDonald, WM Li, XB Bernhardt, ER Haynor, DR Holtzheimer, PE Sackeim, HA George, MS Nahas, Z AF Johnson, Kevin A. Baig, Mirza Ramsey, Dave Lisanby, Sarah H. Avery, David McDonald, William M. Li, Xingbao Bernhardt, Elisabeth R. Haynor, David R. Holtzheimer, Paul E., III Sackeim, Harold A. George, Mark S. Nahas, Ziad TI Prefrontal rTMS for treating depression: Location and intensity results from the OPT-TMS multi-site clinical trial SO BRAIN STIMULATION LA English DT Article DE Transcranial magnetic stimulation (TMS); Imaging (MRI); Motor cortex; Prefrontal cortex; Depression; Classifications; Transcranial Magnetic Stimulation (TMS); Psychiatry ID TRANSCRANIAL MAGNETIC STIMULATION; MOTOR-EVOKED-POTENTIALS; ANTIDEPRESSANT RESPONSE; RESISTANT DEPRESSION; RANDOMIZED-TRIAL; HAND PREFERENCE; CORTEX DISTANCE; COIL PLACEMENT; HUMAN-BRAIN; THRESHOLD AB Background: Motor cortex localization and motor threshold determination often guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings for non-motor brain stimulation. However, anatomic variability results in variability of placement and effective intensity. Objective: Post-study analysis of the OPT-TMS Study reviewed both the final positioning and the effective intensity of stimulation (accounting for relative prefrontal scalp-cortex distances). Methods: We acquired MRI scans of 185 patients in a multi-site trial of left prefrontal TMS for depression. Scans had marked motor sites (localized with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm rule"). Based on a visual determination made before the first treatment, TMS therapy occurred either at the 5 cm location or was adjusted 1 cm forward. Stimulation intensity was 120% of resting motor threshold. Results: The "5 cm rule" would have placed stimulation in premotor cortex for 9% of patients, which was reduced to 4% with adjustments. We did not find a statistically significant effect of positioning on remission, but no patients with premotor stimulation achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor threshold, and no seizures were induced across this range. Patients experienced remission with effective stimulation intensity ranging from 93 to 146% of motor threshold, and we did not find a significant effect of effective intensity on remission. Conclusions: Our data indicates that individualized positioning methods are useful to reduce variability in placement. Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad range of patients. (C) 2013 Elsevier Inc. All rights reserved. C1 [Johnson, Kevin A.; Baig, Mirza; Li, Xingbao; George, Mark S.; Nahas, Ziad] Med Univ S Carolina, Charleston, SC 29425 USA. [Lisanby, Sarah H.; Bernhardt, Elisabeth R.; Sackeim, Harold A.] Columbia Univ, New York, NY 10027 USA. [Avery, David; Haynor, David R.] Univ Washington, Seattle, WA 98195 USA. [McDonald, William M.; Holtzheimer, Paul E., III] Emory Univ, Atlanta, GA 30322 USA. [Johnson, Kevin A.] Stanford Univ, Stanford, CA 94305 USA. [Lisanby, Sarah H.; Bernhardt, Elisabeth R.] Duke Univ, Durham, NC 27706 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Johnson, KA (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. EM johnsk@stanford.edu RI Holtzheimer, Paul/B-6212-2015 OI Holtzheimer, Paul/0000-0002-3552-3296 FU National Institute of Mental Health [5R01 MH069929, 5R01MH069887, 5R01MH 069896, 5R01MH069895, 5R01 MH069886] FX This study was supported by the National Institute of Mental Health as the Optimization of TMS for the Treatment of Depression Study (OPT-TMS) involving grants 5R01 MH069929 (Dr. Avery), 5R01MH069887 (Dr. George), 5R01MH 069896 (Dr. George), 5R01MH069895 (Dr. Lisanby), and 5R01 MH069886 (Dr. McDonald). Following a competitive bid and request involving all TMS manufacturers at the time of trial initiation, Neuronetics Inc was selected and loaned the TMS devices, head holders, and coils for the trial and allowed use of the safety Investigational Device Exemption for their device. NR 61 TC 25 Z9 27 U1 5 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X J9 BRAIN STIMUL JI Brain Stimul. PD MAR PY 2013 VL 6 IS 2 BP 108 EP 117 DI 10.1016/j.brs.2012.02.003 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 115VM UT WOS:000316840000003 PM 22465743 ER PT J AU Biederman, J Petty, CR Hammerness, P Woodworth, KY Faraone, SV AF Biederman, Joseph Petty, Carter R. Hammerness, Paul Woodworth, K. Yvonne Faraone, Stephen V. TI Examining the Nature of the Association Between Attention-Deficit Hyperactivity Disorder and Nicotine Dependence: A Familial Risk Analysis SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE attention-deficit hyperactivity disorder; nicotine dependence; smoking; familial risk ID 10-YEAR FOLLOW-UP; DEFICIT/HYPERACTIVITY DISORDER; DIAGNOSTIC-ACCURACY; UNITED-STATES; SMOKING; ADHD; BEHAVIOR; CIGARETTE; ONSET; GIRLS AB Objective: To use familial risk analysis to examine the association between attention-deficit hyperactivity disorder (ADHD) and nicotine dependence (ND). Method: Subjects were children with (n = 257) and without (n = 229) ADHD of both sexes ascertained from pediatric and psychiatric referral sources and their first-degree relatives (N= 1627). Results: ND in probands increased the risk for ND in relatives irrespective of ADHD status. There was no evidence of cosegregation or assortative mating between these disorders. Patterns of familial risk analysis suggest that the association between ADHD and ND is most consistent with the hypothesis of independent transmission of these disorders. Conclusions: These findings may have important implications for the identification of a subgroup of children with ADHD at high risk for ND based on parental history of ND. C1 [Biederman, Joseph; Petty, Carter R.; Hammerness, Paul; Woodworth, K. Yvonne] Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Petty, Carter R.; Hammerness, Paul; Woodworth, K. Yvonne] Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU United States Public Health Service (National Institute for Child Health and Human Development) [5R01 HD-36317-07]; Lilly Foundation; Pediatric Psychopharmacology Council Fund; Elminda; Janssen; McNeil; Shire; Children's Hospital of Southwest Florida/Lee Memorial Health System; MGH Psychiatry Academy; Abbott; Alza; AstraZeneca; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Company; Esai; Fundacion Areces (Spain); Forest; Glaxo; Gliatech; Hastings Center; Medice Pharmaceuticals (Germany); Merck; Matrix Medical Communications Pediatric; National Alliance for Research in Schizophrenia and Affective Disorders; National Institute on Drug Abuse; New River; National Institute of Child Health and Human Development; National Institute of Mental Health; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry Association; Stanley Foundation; UCB Pharma Inc; Veritas; Wyeth; Ortho-McNeil Janssen; Eli Lilly; Elminda Ltd; GlaxoSmithKline; Johnson Johnson; Takeda; MEN Psychiatry Academy FX The study was supported, in part, by grants awarded to Dr Biederman from the United States Public Health Service (National Institute for Child Health and Human Development) 5R01 HD-36317-07, the Lilly Foundation, and the Pediatric Psychopharmacology Council Fund. Dr Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire. In 2012, he received an honorarium from the Massachussetts General Hospital (MGH) Psychiatry Academy and The Children's Hospital of Southwest Florida/Lee Memorial Health System for tuition-funded continuing medical education (CME) courses. In 2011, he gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, and received honoraria for presenting at international scientific conferences on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. He received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire, and AstraZeneca; these royalties are paid to the Department of Psychiatry at the MGH. In 2010, he received a speaker's fee from a single talk given at Fundacion Dr Manuel Camelo AC in Monterrey, Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc and Cipher Pharmaceuticals Inc; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. He also received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In previous years, he received research support, consultation fees, or speaker's fees for or from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Company, Esai, Fundacion Areces (Spain), Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, Matrix Medical Communications Pediatric, National Alliance for Research in Schizophrenia and Affective Disorders, National Institute on Drug Abuse, New River, National Institute of Child Health and Human Development, National Institute of Mental Health, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc, Veritas, and Wyeth.; In the past 2 years, Dr Hammemess has participated in CME activities or professional talks supported by Ortho-McNeil Janssen and Shire, served on the advisory board for Shire, and participated, as an investigator or principal investigator, in research studies funded by Cephalon, Eli Lilly, Elminda Ltd, GlaxoSmithKline, Johnson & Johnson, McNeil, Merck, New River, Novartis, Ortho-McNeil Janssen, Pfizer, Shire, and Takeda. He has also received honoraria from commercial entities supporting the MEN Psychiatry Academy.; In the past year, Dr Faraone received consulting income and research support from Shire and Alcobra and research support from the National Institutes of Health. In previous years, he received consulting fees or was on advisory boards or participated in CME programs sponsored by Shire, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. He receives royalties from books published by Guilford Press (Straight Talk About Your Child's Menial Health) and Oxford University Press (Schizophrenia.. The Facts). Mr Petty and Ms Woodworth do not have any conflicts of interest to disclose. NR 36 TC 1 Z9 1 U1 3 U2 7 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 MAR PY 2013 VL 58 IS 3 BP 177 EP 183 PG 7 WC Psychiatry SC Psychiatry GA 117BX UT WOS:000316928200008 PM 23461889 ER PT J AU Yamaguchi, S Hong, K Liu, R Inoue, A Shen, L Zhang, K Zhang, Y AF Yamaguchi, Shinpei Hong, Kwonho Liu, Rui Inoue, Azusa Shen, Li Zhang, Kun Zhang, Yi TI Dynamics of 5-methylcytosine and 5-hydroxymethylcytosine during germ cell reprogramming SO CELL RESEARCH LA English DT Article DE DNA demethylation; 5-hydroxymethylcytosine; primordial germ cells; reprogramming; pericentric heterochromatin ID MOUSE PREIMPLANTATION DEVELOPMENT; ACTIVE DNA DEMETHYLATION; BASE EXCISION-REPAIR; MAMMALIAN DNA; TET PROTEINS; METHYLATION; SPECIFICATION; MICE; MECHANISMS; 5-CARBOXYLCYTOSINE AB Previous studies have revealed that mouse primordial germ cells (PGCs) undergo genome-wide DNA methylation reprogramming to reset the epigenome for totipotency. However, the precise 5-methylcytosine (5mC) dynamics and its relationship with the generation of 5-hydroxymethylcytosine (5hmC) are not clear. Here we analyzed the dynamics of 5mC and 5hmC during PGC reprograming and germ cell development. Unexpectedly, we found a specific period (E8.5-9.5) during which both 5mC and 5hmC levels are low. Subsequently, 5hmC levels increase reaching its peak at E11.5 and gradually decrease until E13.5 likely by replication-dependent dilution. Interestingly, 5hmC is enriched in chromocenters during this period. While this germ cell-specific 5hmC subnuclear localization pattern is maintained in female germ cells even in mature oocytes, such pattern is gradually lost in male germ cells as mitotic proliferation resumes during the neonatal stage. Pericentric 5hmC plays an important role in silencing major satellite repeat, especially in female PGCs. Global transcriptome analysis by RNA-seq revealed that the great majority of differentially expressed genes from E9.5 to 13.5 are upregulated in both male and female PGCs. Although only female PGCs enter meiosis during the prenatal stage, meiosis-related and a subset of imprinted genes are significantly upregulated in both male and female PGCs at E13.5. Thus, our study not only reveals the dynamics of 5mC and 5hmC during PGC reprogramming and germ cell development, but also their potential role in epigenetic reprogramming and transcriptional regulation of meiotic and imprinted genes. C1 [Yamaguchi, Shinpei; Hong, Kwonho; Inoue, Azusa; Shen, Li; Zhang, Yi] Howard Hughes Med Inst, Boston, MA 02115 USA. [Yamaguchi, Shinpei; Hong, Kwonho; Inoue, Azusa; Shen, Li; Zhang, Yi] Boston Childrens Hosp, Dept Pediat, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yamaguchi, Shinpei; Hong, Kwonho; Inoue, Azusa; Shen, Li; Zhang, Yi] Boston Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Liu, Rui; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Zhang, Y (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu OI Yamaguchi, Shinpei/0000-0002-9377-4835 FU NIH [R01GM097253]; CIRM [RB3-05083, GM68804, U01DK089565] FX We thank Jinzhao Wang and Wei Jiang for FACS sorting; Ho-Lim Fung for Illumina sequencing; Susan Wu and Gustavo German for critical reading of the manuscript. This work was partially supported by NIH R01GM097253 and CIRM RB3-05083 (to KZ); and GM68804 and U01DK089565 (to YZ). YZ is an Investigator of the Howard Hughes Medical Institute. NR 35 TC 55 Z9 57 U1 1 U2 33 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD MAR PY 2013 VL 23 IS 3 BP 329 EP 339 DI 10.1038/cr.2013.22 PG 11 WC Cell Biology SC Cell Biology GA 109NJ UT WOS:000316375000007 PM 23399596 ER PT J AU Yaghootkar, H Lamina, C Scott, R Dastani, Z Hivert, MF Lawlor, D Meigs, J Richards, B Frayling, T AF Yaghootkar, H. Lamina, C. Scott, R. Dastani, Z. Hivert, M. F. Lawlor, D. Meigs, J. Richards, B. Frayling, T. CA ADIPOGen Consortium TI Mendelian randomisation studies do not support a causal role for reduced circulating adiponectin levels in fasting based measures of insulin resistance and Type 2 diabetes SO DIABETIC MEDICINE LA English DT Meeting Abstract C1 [Yaghootkar, H.; Frayling, T.] Peninsula Coll Med & Dent, PCMD, Exeter, Devon, England. [Lamina, C.] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria. [Scott, R.] Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. [Dastani, Z.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3T 1E2, Canada. [Hivert, M. F.] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Lawlor, D.] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Hivert, M. F.; Meigs, J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Richards, B.] McGill Univ, Dept Med Human Genet Epidemiol & Biostat, Montreal, PQ, Canada. [Richards, B.] Kings Coll London, London WC2R 2LS, England. NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAR PY 2013 VL 30 SU 1 SI SI BP 30 EP 30 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108AQ UT WOS:000316263400104 ER PT J AU Marullo, L Dupuis, J Scapoli, C Meigs, JB Morris, A Prokopenko, I AF Marullo, L. Dupuis, J. Scapoli, C. Meigs, J. B. Morris, A. Prokopenko, I. TI Impact of Type 2 diabetes susceptibility loci on variation in multiple cardio-metabolic traits SO DIABETIC MEDICINE LA English DT Meeting Abstract C1 [Marullo, L.; Scapoli, C.] Univ Ferrara, Dept Life Sci & Biotechnol, I-44100 Ferrara, Italy. [Marullo, L.; Morris, A.; Prokopenko, I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Dupuis, J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, J. B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Prokopenko, I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. RI Scapoli, Chiara/E-2268-2015 OI Scapoli, Chiara/0000-0003-4058-4787 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAR PY 2013 VL 30 SU 1 SI SI BP 51 EP 51 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108AQ UT WOS:000316263400161 ER PT J AU Tobi, M Kim, M Weinstein, DH Rambus, MA Hatfield, J Adsay, NV Levi, E Evans, D Lawson, MJ Fligiel, S AF Tobi, Martin Kim, Mijin Weinstein, Douglas H. Rambus, Mary Ann Hatfield, James Adsay, N. Volkan Levi, Edi Evans, Douglas Lawson, Michael J. Fligiel, Suzanne TI Prospective Markers for Early Diagnosis and Prognosis of Sporadic Pancreatic Ductal Adenocarcinoma SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Pancreatic ductal adenocarcinoma (PDA); Adnab-9 monoclonal antibody; K-ras; Her-2/neu ID MONOCLONAL-ANTIBODY ADNAB-9; COLORECTAL NEOPLASIA; MOLECULAR MARKERS; REG-I; CANCER; RISK; CARCINOMA; LESIONS; GENE; PRECURSORS AB Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. No proven screening strategies are available and frequent cross-sectional imaging studies (CT/MRI) are impractical even in patients thought to be at higher risk than the general population. Few PDA biomarkers have been studied prospectively for screening. Here, we prospectively evaluated the Adnab-9 monoclonal antibody in stool, pancreaticobiliary secretions, and tissue for screening and prognostic value in sporadic PDA. We also evaluated the prognostic value of characterized early biomarkers in pancreaticobiliary secretions. Adnab-9 diagnostic ability was tested in stool in 249 and 1,132 patients from China and the US, respectively. Immunohistochemistry was performed in 22 tissue samples with Adnab-9 antibody and anti-Defensin 5, a constituent of Paneth cells. Pancreatobiliary secretions were collected from 12 PDA patients and 9 controls. The enriched PCR method was performed to detect K-ras mutations. ELISA was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti-Reg I). Adnab-9 alone was diagnostic and prognostic when measured in pancreatic secretions, feces, and tissues of PDA patients compared to controls (p < 0.05). Significantly, Adnab-9 fecal binding can precede the clinical diagnosis by 2.3 years, potentially allowing earlier clinical intervention. In pancreatic secretions, a combination of K-ras and Her-2/neu when appropriately standardized can be diagnostic in 75 % of PDA. Our study suggests that Adnab-9 may be an effective marker for diagnosis and prognosis of PDA. Adnab-9 may be reflective of the presence of Paneth cells confirmed by Defensin-5 staining. These cells may modulate the biological activity of the cancer and confer a better prognosis. C1 [Tobi, Martin; Weinstein, Douglas H.] Philadelphia Vet Affairs Med Ctr, Gastroenterol Sect, Philadelphia, PA USA. [Tobi, Martin; Kim, Mijin] Univ Penn, Sch Med, Dept Med, Div Gastroenterol,PVAMC Med GI 3, Philadelphia, PA 19104 USA. [Tobi, Martin; Rambus, Mary Ann; Hatfield, James; Adsay, N. Volkan; Levi, Edi; Fligiel, Suzanne] Wayne State Univ, Sch Med, John D Dingell Vet Affairs Med Ctr, Dept Med & Pathol, Detroit, MI USA. [Evans, Douglas] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lawson, Michael J.] Univ Calif, Kaiser Permanente, Sacramento, CA USA. RP Tobi, M (reprint author), Univ Penn, Sch Med, Dept Med, Div Gastroenterol,PVAMC Med GI 3, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Martin.Tobi@va.gov FU Veterans Administration; Kaiser Permanente Research Foundation FX The authors wish to thank Dr. Vaitkevicius and Pat Arluskas for providing tissue blocks, and Dr. M.N. Ehrinpreis for his assistance with the preparation of this manuscript. We are grateful to Drs. Ralph Hruban, James Abbruzzese, Mei Yuan and Daniel Longnecker for study material and Dr. Ben Stanger for the internal review of this manuscript. This paper is dedicated to the memory of Chaim "Denis" Tobiansky. This study was supported in part by grants from the Veterans Administration and the Kaiser Permanente Research Foundation. NR 40 TC 2 Z9 3 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2013 VL 58 IS 3 BP 744 EP 750 DI 10.1007/s10620-012-2387-x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 119DF UT WOS:000317076700024 PM 23001406 ER PT J AU Tolstykh, GP Cavazos, JE AF Tolstykh, Gleb P. Cavazos, Jose E. TI Potential mechanisms of sudden unexpected death in epilepsy SO EPILEPSY & BEHAVIOR LA English DT Review DE SUDEP; Neuron loss; NTS; Nucleus of the solitary tract; KCNK channels ID BLOOD-PRESSURE VARIABILITY; NUCLEUS-TRACTUS-SOLITARIUS; FIBER SYNAPTIC REORGANIZATION; LIMBIC CORTICAL SEIZURES; KCNQ POTASSIUM CHANNELS; KAINIC ACID; BAROREFLEX SENSITIVITY; ORGAN DAMAGE; HEART-RATE; CARDIAC REPOLARIZATION AB Sudden unexpected death in epilepsy (SUDEP) accounts for 15% of all deaths in people with epilepsy and 50% in refractory epilepsy. The underlying mechanisms are not well understood, but seizure-induced cardiac and respiratory arrests are involved. The cardiovascular and respiratory systems are subject to precise reflex regulation to ensure appropriate oxygen supply under a wide range of circumstances. Barosensory and chemosensory afferents project into the nucleus tractus solitarius (NTS), which relays systemic data to higher brain centers for integration of homeostatic responses in heart rate, peripheral resistance, respiration, and other autonomic reactions. Being the afferent autonomic gatekeeper, NTS plays a critical role in cardiovascular and respiratory regulation. In the course of studying the kainic acid model, we became aware of progressive neuronal loss in the NTS and noted SUDEP-like deaths in rats with frequent convulsions. Increased autonomic susceptibility with inhalation anesthetics was also observed, often seen after impairment of baroreceptor and chemoreceptor reflex loops. Seizure-induced neuron loss in NTS may play a role impairing the integrative functions of NTS resulting in poor homeostatic responses during seizures and leading to SUDEP. This article is part of a Special Issue entitled "The Future of Translational Epilepsy Research". Published by Elsevier Inc. C1 [Tolstykh, Gleb P.; Cavazos, Jose E.] South Texas Vet Hlth Care Syst, Res Div ALM VAMC, San Antonio, TX USA. [Tolstykh, Gleb P.; Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Tolstykh, Gleb P.; Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Tolstykh, Gleb P.; Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Cavazos, Jose E.] South Texas Vet Hlth Care Syst, San Antonio VA Epilepsy Ctr Excellence, San Antonio, TX USA. [Cavazos, Jose E.] South Texas Vet Hlth Care Syst, Div Res, San Antonio, TX USA. RP Cavazos, JE (reprint author), Audie L Murphy VA Hosp, Neurol Sect, Mail Code 111D,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM cavazosj@uthscsa.edu RI Cavazos, Jose/J-4122-2016; OI Cavazos, Jose/0000-0001-5777-2608 NR 95 TC 22 Z9 22 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAR PY 2013 VL 26 IS 3 BP 410 EP 414 DI 10.1016/j.yebeh.2012.09.017 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 113JU UT WOS:000316663900026 PM 23305781 ER PT J AU Verrier, RL Kumar, K Nieminen, T Belardinelli, L AF Verrier, Richard L. Kumar, Kapil Nieminen, Tuomo Belardinelli, Luiz TI Mechanisms of ranolazine's dual protection against atrial and ventricular fibrillation SO EUROPACE LA English DT Review DE Ranolazine; T-wave alternans; Ventricular fibrillation; Atrial fibrillation; Sodium current ID LATE SODIUM CURRENT; RANDOMIZED CONTROLLED-TRIAL; CURRENT BLOCKER RANOLAZINE; ACUTE-CORONARY-SYNDROME; INTACT PORCINE HEART; T-WAVE ALTERNANS; LATE NA+ CURRENT; CURRENT INHIBITION; ANTIANGINAL AGENT; CHRONIC ANGINA AB Coronary artery disease and heart failure carry concurrent risk for atrial fibrillation and life-threatening ventricular arrhythmias. We review evidence indicating that at therapeutic concentrations, ranolazine has potential for dual suppression of these arrhythmias. Mechanisms and clinical implications are discussed. C1 [Verrier, Richard L.; Kumar, Kapil] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kumar, Kapil] Harvard Vanguard Med Associates, Boston, MA USA. [Nieminen, Tuomo] Univ Helsinki, Helsinki Univ Cent Hosp, FIN-00014 Helsinki, Finland. [Belardinelli, Luiz] Gilead Sci Inc, Foster City, CA 94404 USA. RP Verrier, RL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,Harvard Thorndike Electrophysi, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu OI Nieminen, Tuomo/0000-0003-1755-1688 FU Gilead Sciences, Inc. FX R.L.V. receives research grant support from Gilead Sciences, Inc. NR 64 TC 23 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD MAR PY 2013 VL 15 IS 3 BP 317 EP 324 DI 10.1093/europace/eus380 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 111RG UT WOS:000316537800005 PM 23220484 ER PT J AU Kron, J Sauer, W Schuller, J Bogun, F Crawford, T Sarsam, S Rosenfeld, L Mitiku, TY Cooper, JM Mehta, D Greenspon, AJ Ortman, M Delurgio, DB Valadri, R Narasimhan, C Swapna, N Singh, JP Danik, S Markowitz, SM Almquist, AK Krahn, AD Wolfe, LG Feinstein, S Ellenbogen, KA AF Kron, Jordana Sauer, William Schuller, Joseph Bogun, Frank Crawford, Thomas Sarsam, Sinan Rosenfeld, Lynda Mitiku, Teferi Y. Cooper, Joshua M. Mehta, Davendra Greenspon, Arnold J. Ortman, Matthew Delurgio, David B. Valadri, Ravinder Narasimhan, Calambur Swapna, Nalla Singh, Jagmeet P. Danik, Stephan Markowitz, Steven M. Almquist, Adrian K. Krahn, Andrew D. Wolfe, Luke G. Feinstein, Shawn Ellenbogen, Kenneth A. TI Efficacy and safety of implantable cardiac defibrillators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis SO EUROPACE LA English DT Article DE Implantable cardiac defibrillator; Cardiac sarcoidosis ID LEAD FAILURE; STIMULATION; THERAPY; DEVICE AB Aims Implantable cardiac defibrillator (ICD) implantation is a class IIA recommendation for patients with cardiac sarcoidosis (CS). However, little is known about the efficacy and safety of ICDs in this population. The goal of this multi-centre retrospective data review was to evaluate the efficacy and safety of ICDs in patients with CS. Methods and results Electrophysiologists at academic medical centres were asked to identify consecutive patients with CS and an ICD. Clinical information, ICD therapy history, and device complications were collected for each patient. Data were collected on 235 patients from 13 institutions, 64.7% male with mean age 55.6 +/- 11.1. Over a mean follow-up of 4.2 +/- 4.0 years, 85 of 234 (36.2%) patients received an appropriate ICD therapy (shocks and/or anti-tachycardia pacing) and 67 of 226 (29.7%) received an appropriate shock. Fifty-seven of 235 patients (24.3%) received a total of 222 inappropriate shocks. Forty-six adverse events occurred in 41 of 235 patients (17.4%). Patients who received appropriate ICD therapies were more likely to be male (73.8 vs. 59.6%, P = 0.0330), have a history of syncope (40.5 vs. 22.5%, P = 0.0044), lower left ventricular ejection fraction (38.1 +/- 15.2 vs. 48.8 +/- 14.7%, P <= 0.0001), ventricular pacing on baseline electrocardiogram (16.1 vs. 2.1%, P = 0.0002), and a secondary prevention indication (60.7 vs. 24.5%, P < 0.0001) compared with those who did not receive appropriate ICD therapies. Conclusion Patients with CS and ICDs are at high risk for ventricular arrhythmias. This population also has high rates of inappropriate shocks and device complications. C1 [Kron, Jordana; Feinstein, Shawn; Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Dept Cardiac Electrophysiol, Richmond, VA 23298 USA. [Sauer, William; Schuller, Joseph] Univ Colorado, Dept Cardiol, Denver, CO 80202 USA. [Bogun, Frank; Crawford, Thomas; Sarsam, Sinan] Univ Michigan, Dept Cardiol, Ann Arbor, MI 48109 USA. [Rosenfeld, Lynda; Mitiku, Teferi Y.] Yale Univ, Dept Cardiac Electrophysiol, New Haven, CT USA. [Cooper, Joshua M.] Univ Penn, Dept Cardiol, Philadelphia, PA 19104 USA. [Mehta, Davendra] Mt Sinai Hosp, Dept Cardiol, New York, NY 10029 USA. [Greenspon, Arnold J.; Ortman, Matthew] Thomas Jefferson Univ Hosp, Div Cardiol, Philadelphia, PA 19107 USA. [Delurgio, David B.; Valadri, Ravinder] Emory Univ, Dept Cardiol, Atlanta, GA 30322 USA. [Narasimhan, Calambur; Swapna, Nalla] CARE Hosp, Dept Cardiol, Hyderabad, Andhra Pradesh, India. [Singh, Jagmeet P.; Danik, Stephan] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Markowitz, Steven M.] Weill Cornell Med Ctr, Dept Cardiol, New York, NY USA. [Almquist, Adrian K.] Minneapolis Heart Inst, Dept Cardiol, Minneapolis, MN USA. [Krahn, Andrew D.] Univ Western Ontario, Div Cardiol, London, ON, Canada. [Wolfe, Luke G.] Virginia Commonwealth Univ, Dept Gen Surg, Richmond, VA 23298 USA. RP Kron, J (reprint author), Virginia Commonwealth Univ, Med Ctr, POB 980053, Richmond, VA 23298 USA. EM jkron@mcvh-vcu.edu FU Medtronic Inc.; St. Jude Medical; Boston Scientific Corp; Cardiovascular Center at the University of Michigan for development of cardiac sarcoidosis registry; Boston Scientific; Boston Scientific Corp.; Biotronik; CardioInsight Inc.; Thoratec Inc.; Biosense Webster; Biosense Web; Sanofi FX J.K. has reported that she has no relationships relevant to the contents of this paper to disclose. W.S. has reported that he received education grants for EP fellowship and consulting fees from Medtronic Inc., St. Jude Medical, and Boston Scientific Corp. J.S. has reported that he has no relationships relevant to the contents of this paper to disclose. F.B. has reported that he has no relationships relevant to the contents of this paper to disclose. T.C. has received grant support from Cardiovascular Center at the University of Michigan for development of cardiac sarcoidosis registry. S.S. has reported that he has no relationships relevant to the contents of this paper to disclose. L.R. has reported that she has received fellowship support from Medtronic Inc., Boston Scientific, and St. Jude Medical. T.Y.M. has reported that he has no relationships relevant to the contents of this paper to disclose. J.M.C. has received honoraria from Medtronic Inc., Boston Scientific, Biotronik, St. Jude Medical, and Spectranetics. D.M. has reported that he has no relationships relevant to the contents of this paper to disclose. A.J.G. has received honoraria from Medtronic Inc., Boston Scientific, and St. Jude Medical. M.O. has received speaking fees from St. Jude Medical and Boston Scientific. D.B.D. has reported that he has no relationships relevant to the contents of this paper to disclose. R.V. has reported that he has no relationships relevant to the contents of this paper to disclose. C.N. has reported that he has no relationships relevant to the contents of this paper to disclose. N.S. has reported that she has no relationships relevant to the contents of this paper to disclose. J.P.S. has reported that he received research grants from St. Jude Medical, Medtronic Inc., Boston Scientific Corp., and Biotronik; consultant fees from Boston Scientific Corp., Biotronik, St. Jude Medical, Medtronic Inc., CardioInsight Inc., Thoratec Inc., and Biosense Webster; honoraria from Medtronic Inc., Biotronik, Guidant Corp., St Jude Medical, and Sorin Group. S.D. has reported consultant fees from St. Jude Medical, Boston Scientific. S.M.M. has received honoraria from Medtronic Inc., St. Jude Medical, Biotronik, and Sanofi-Aventis. A.K.A. has reported that he has no relationships relevant to the contents of this paper to disclose. A.D.K. has reported that he has no relationships relevant to the contents of this paper to disclose. L.G.W. has reported that he has no relationships relevant to the contents of this paper to disclose. S.F. has reported that he has no relationships relevant to the contents of this paper to disclose. K.A.E. has received honoraria from Medtronic Inc., Boston Scientific, and Cameron Medical; speaking fees from Medtronic Inc., Boston Scientific, St. Jude Medical, Biotronik, and Sanofi; research grants from Medtronic Inc., Boston Scientific, Biosense Web, and Sanofi; fellowship support from Medtronic Inc., Boston Scientific, and Biosense Web. NR 18 TC 34 Z9 34 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD MAR PY 2013 VL 15 IS 3 BP 347 EP 354 DI 10.1093/europace/eus316 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 111RG UT WOS:000316537800010 PM 23002195 ER PT J AU Coffey, JO d'Avila, A Dukkipati, S Danik, SB Gangireddy, SR Koruth, JS Miller, MA Sager, SJ Eggert, CA Reddy, VY AF Coffey, James O. d'Avila, Andre Dukkipati, Srinivas Danik, Stephan B. Gangireddy, Sandeep R. Koruth, Jacob S. Miller, Marc A. Sager, Solomon J. Eggert, Charles A. Reddy, Vivek Y. TI Catheter ablation of scar-related atypical atrial flutter SO EUROPACE LA English DT Article DE Catheter ablation; Scar-related atrial flutter; Multielectrode mapping; Long-term results ID PULMONARY VEIN ABLATION; ELECTROPHYSIOLOGICAL CHARACTERISTICS; FIBRILLATION ABLATION; TACHYCARDIA; ARRHYTHMIAS; MECHANISMS; ISTHMUS AB Aims The aim of the study was to assess the impact of isthmus location of atypical atrial flutters/atrial tachycardias (ATs) on outcomes of catheter ablation. Atrial tachycardias are clinically challenging arrhythmias that can occur in the presence of atrial scar often due to either cardiac surgery or prior ablation for atrial fibrillation. We previously demonstrated a catheter ablation approach employing rapid multielectrode activation mapping with targeted entrainment manoeuvrs. However, the role that AT isthmus location plays in acute and long-term success of ablation remains uncertain. Methods and results Retrospective multicenter analysis of 91 consecutive AT patients undergoing ablation using a systematic four-step approach: (i) high-density activation mapping; (ii) analysis of atrial activation to identify wavefronts of electrical propagation; (iii) targeted entrainment of putative channels; and (iv) irrigated radiofrequency ablation of constrained regions of the circuit. Clinical outcomes, procedural details, and clinical profiles were determined. A total of 171 ATs (1.9 +/- 1.0 per patient, 26% septal ATs) were targeted for ablation. The acute success rates were 97 and 77% for patients with either non-septal ATs or septal ATs, respectively (P = 0.0023). Similarly, the long-term success rates, were 82 and 67% for patients with either no septal ATs or at least one septal AT, respectively (P = 0.1057). The long-term success rates were 75, 88, and 57% for patients with ATs associated with prior catheter ablation, cardiac surgery or MAZE, and idiopathic atrial scar, respectively. Conclusion Catheter ablation of AT can be successfully performed employing a strategy of combined high-density activation and entrainment mapping. Septal ATs are associated with higher rates of acute and long-term recurrences. C1 [Coffey, James O.; d'Avila, Andre; Dukkipati, Srinivas; Gangireddy, Sandeep R.; Koruth, Jacob S.; Miller, Marc A.; Reddy, Vivek Y.] Mt Sinai Sch Med, Helmsley Electrophysiol Ctr, New York, NY 10029 USA. [Danik, Stephan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Sager, Solomon J.] Univ Miami, Med Ctr, Miami, FL USA. [Eggert, Charles A.] St Jude Med SC Inc, St Paul, MN USA. RP Reddy, VY (reprint author), Mt Sinai Sch Med, Helmsley Electrophysiol Ctr, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM vivek.reddy@mountsinai.org RI d'Avila, Andre/F-8009-2010 OI d'Avila, Andre/0000-0001-8769-1411 FU St Jude Medical; Biosense Webster FX A.d'A. and V.Y.R. have received consulting fees, speaker honorarium, and grant support from St Jude Medical, the manufacturer of the electroanatomic mapping system, and Biosense Webster, the manufacturer of the ablation catheter used in this series. S.D. has received research grant support from Biosense Webster. C.A.E. is an employee of St Jude Medical. The remaining authors report no conflicts of interest. No external funding was utilized in this research or in the development of this manuscript. NR 18 TC 15 Z9 15 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD MAR PY 2013 VL 15 IS 3 BP 414 EP 419 DI 10.1093/europace/eus312 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 111RG UT WOS:000316537800023 PM 23385050 ER PT J AU Chen, LC McKenna, JT Bolortuya, Y Brown, RE McCarley, RW AF Chen, Lichao McKenna, James T. Bolortuya, Yunren Brown, Ritchie E. McCarley, Robert W. TI Knockdown of orexin type 2 receptor in the lateral pontomesencephalic tegmentum of rats increases REM sleep SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE diurnal; hypocretin; narcolepsy; RNA interference; siRNA ID PARADOXICAL SLEEP; PERIAQUEDUCTAL GRAY; MESSENGER-RNA; KNOCKOUT MICE; NARCOLEPSY; NEURONS; EXPRESSION; PROTEIN; BRAIN; GENE AB Dysfunction of the orexin/hypocretin neurotransmitter system causes the sleep disorder narcolepsy, characterized by intrusion of rapid eye movement (REM) sleep-like events into normal wakefulness. The sites where orexins act to suppress REM sleep are incompletely understood. Previous studies suggested that the lateral pontomesencephalic tegmentum (lPMT) contains an important REM sleep inhibitory area, and proposed that orexins inhibit REM sleep via orexin type 2 receptors (OxR2) in this region. However, this hypothesis has heretofore not been tested. We thus performed bilateral injection of small interfering RNAs (siRNAs) targeting Ox2R into the lPMT on two consecutive days. This led to a approximately 30% increase of time spent in REM sleep in both the dark and light periods for the first 2days after injection, with a return to baseline over the next two post-injection days. This increase was mainly due to longer (>120s) REM episodes. Cataplexy-like episodes were not observed. The percentage of time spent in wakefulness and non-(N)REM sleep, as well as the power spectral profile of NREM and REM sleep, were unaffected. Control animals injected with scrambled siRNA had no sleep changes post-injection. Quantification of the knockdown revealed that unilateral microinjection of siRNAs targeting OxR2 into the lPMT induced a approximately 40% reduction of OxR2 mRNA 2days following the injections when compared with the contralateral side receiving control (scrambled) siRNA. Orexin type 1 receptor mRNA level was unaffected. Our results indicate that removal of OxR2 neurotransmission in the lPMT enhances REM sleep by increasing the duration of REM episodes. C1 [Chen, Lichao; McKenna, James T.; Bolortuya, Yunren; Brown, Ritchie E.; McCarley, Robert W.] VA Boston Healthcare Syst, Res Serv, Brockton, MA USA. [Chen, Lichao; McKenna, James T.; Bolortuya, Yunren; Brown, Ritchie E.; McCarley, Robert W.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. RP Chen, LC (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. EM lichao_chen@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Brown, Ritchie/0000-0002-7164-4132 FU VA (Merit Award); NIH [R01 MH39683, P01 HL095491, R21 MH094803]; VA MERIT grant FX This study was supported by VA (Merit Award to R.W.M.), and NIH grants R01 MH39683, P01 HL095491 (R.W.M.) and R21 MH094803 (R.E.B.). The authors would like to thank Courtney Birchall, Mike Leonard and Ryan Perry for their technical assistance. We also thank Dr Robert Strecker for the support of his VA MERIT grant, and his effort in providing the staff and resources needed to perform surgery and sleep data analysis for this project. The authors declare no conflict of interest. NR 37 TC 5 Z9 5 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2013 VL 37 IS 6 BP 957 EP 963 DI 10.1111/ejn.12101 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 110UC UT WOS:000316471200009 PM 23282008 ER PT J AU Niessner, H Forschner, A Klumpp, B Honegger, JB Witte, M Bornemann, A Dummer, R Adam, A Bauer, J Tabatabai, G Flaherty, K Beck, D Leiter, U Mauch, C Rosch, A Weide, B Eigentler, T Schadendorf, D Garbe, C Kulms, D Quintanilla-Martinez, L Meier, F AF Niessner, H. Forschner, A. Klumpp, B. Honegger, J. B. Witte, M. Bornemann, A. Dummer, R. Adam, A. Bauer, J. Tabatabai, G. Flaherty, K. Beck, D. Leiter, U. Mauch, C. Roesch, A. Weide, B. Eigentler, T. Schadendorf, D. Garbe, C. Kulms, D. Quintanilla-Martinez, L. Meier, F. TI Targeting hyperactivation of the AKT survival pathway to overcome therapy resistance of melanoma brain metastases SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Association-of-Dermatological-Research CY MAR 14-16, 2013 CL Dessau, GERMANY SP Assoc Dermatolog Res C1 [Niessner, H.; Forschner, A.; Bauer, J.; Beck, D.; Leiter, U.; Weide, B.; Eigentler, T.; Garbe, C.; Meier, F.] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany. [Klumpp, B.] Univ Tubingen, Dept Diagnost & Intervent Radiol, D-72076 Tubingen, Germany. [Honegger, J. B.] Univ Tubingen, Dept Neurosurg, D-72076 Tubingen, Germany. [Witte, M.] Univ Tubingen, Dept Surg, D-72076 Tubingen, Germany. [Bornemann, A.] Univ Tubingen, Dept Neuropathol, D-72076 Tubingen, Germany. [Dummer, R.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Adam, A.; Quintanilla-Martinez, L.] Univ Tubingen, Inst Pathol, D-72076 Tubingen, Germany. [Tabatabai, G.] Univ Zurich, Dept Neurol, CH-72076 Zurich, Switzerland. [Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mauch, C.] Univ Cologne, Dept Dermatol, Cologne, Germany. [Roesch, A.] Univ Homburg, Dept Dermatol, Bad Homburg, Germany. [Schadendorf, D.] Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. [Kulms, D.] Univ Dresden, Dept Dermatol, Dresden, Germany. RI Kulms, Dagmar/H-1653-2014; Eigentler, Thomas/K-8570-2015 OI Eigentler, Thomas/0000-0003-0019-2770 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2013 VL 22 IS 3 BP E38 EP E38 PG 1 WC Dermatology SC Dermatology GA 108YJ UT WOS:000316332000228 ER PT J AU Hideshima, T Anderson, KC AF Hideshima, Teru Anderson, Kenneth C. TI Histone deacetylase inhibitors in the treatment for multiple myeloma SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Multiple myeloma; Histone deacetylase (HDAC); HDAC inhibitor; Proteasome inhibitor ID SUBEROYLANILIDE HYDROXAMIC ACID; CHRONIC LYMPHOCYTIC-LEUKEMIA; CELL LUNG-CANCER; PHASE-I TRIAL; DEPSIPEPTIDE FR901228; HDAC INHIBITOR; FK228 DEPSIPEPTIDE; ANTITUMOR-ACTIVITY; LBH589; COMBINATION AB Histone lysine acetylation is regulated by both histone deacetylases (HDACs) and histone acetyl transferases. Inhibition of deacetylases induces hyperacetylate of target proteins and has a crucial role in the epigenetic regulation of gene expression mediating cell survival and proliferation. Therefore, HDAC inhibitors have emerged as novel therapeutic agents for cancers, including multiple myeloma (MM). Recent studies revealed that HDAC inhibitors trigger hyperacetylation of not only histones, but also non-histone proteins regulating cell growth and survival, revealing the complexity of mechanism of action of HDAC inhibitors. Many HDAC inhibitors have already shown significant anti-MM activities in preclinical studies and are under evaluation in clinical trials. C1 [Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Hideshima, T (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM teru_hideshima@dfci.harvard.edu; kennth_anderson@dfci.harvard.edu FU NCI NIH HHS [P01 CA155258, P50 CA100707, P01 CA078378] NR 48 TC 12 Z9 13 U1 1 U2 14 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD MAR PY 2013 VL 97 IS 3 BP 324 EP 332 DI 10.1007/s12185-013-1290-3 PG 9 WC Hematology SC Hematology GA 109EB UT WOS:000316347600005 PM 23475757 ER PT J AU Stryjewski, TP Vavvas, DG AF Stryjewski, Tomasz P. Vavvas, Demetrios G. TI Genetic Correlates of Proliferative Vitreoretinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Editorial Material C1 [Stryjewski, Tomasz P.; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02115 USA. RP Stryjewski, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02115 USA. EM vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 2 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2013 VL 54 IS 3 BP 1679 EP 1679 DI 10.1167/iovs.12-11508 PG 1 WC Ophthalmology SC Ophthalmology GA 117GV UT WOS:000316942400013 ER PT J AU Sheetz, MJ Aiello, LP Davis, MD Danis, R Bek, T Cunha-Vaz, J Shahri, N Berg, PH AF Sheetz, Matthew J. Aiello, Lloyd Paul Davis, Matthew D. Danis, Ronald Bek, Toke Cunha-Vaz, Jose Shahri, Nazila Berg, Paul H. CA MBDL Study Grp MBCU Study Grp TI The Effect of the Oral PKC beta Inhibitor Ruboxistaurin on Vision Loss in Two Phase 3 Studies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PROTEIN-KINASE-C; NONPROLIFERATIVE DIABETIC-RETINOPATHY; VISUAL-LOSS; CLINICAL-TRIAL; MACULAR EDEMA; GROWTH-FACTOR; COMPLICATIONS; LY333531; SAFETY; RATS AB PURPOSE. To assess the effect of ruboxistaurin (RBX) on vision loss through a prospectively defined combined analysis of two phase 3 trials (MBDL and MBCU). METHODS. Patients in both of these 3-year randomized, placebo-controlled, double-masked trials had best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) >= 75 letters (similar to 20/32 Snellen), ETDRS retinopathy level 20 to 47D (MBDL) or 35B to 53E (MBCU), and no prior panretinal or focal photocoagulation in at least one eye at baseline. Patients received oral placebo (N = 508 total from both studies) or RBX 32 mg/d (N = 520 total). Best-corrected ETDRS VA was measured at 6-month intervals for 3 years (MBDL) or for 18 to 48 months (MBCU). Sustained moderate visual loss (SMVL) was defined as a 15-letter or more reduction from baseline in VA sustained for a patient's last 6 months of study participation. RESULTS. In the combined studies (N = 1028 total), SMVL occurred in 4.4% of placebo-versus 2.3% of RBX-treated patients (P - 0.069). In patients with a minimum of 2 years of follow-up (N = 825 total), there was less SMVL in the RBX group (4.4% placebo versus 2.1% RBX, P = 0.045). Other VA-related measures (mean VA, contrast sensitivity, Visual Functioning Questionnaire 25 [VFQ-25]) either trended toward a benefit for RBX or were also statistically significant in favor of RBX. In contrast, diabetic macular edema (DME) morphology-related measures (occurrence of significant center of macula involvement, optical coherence tomography [OCT]-determined center of macula thickness, application of focal photocoagulation) did not show a consistent trend in favor of or against RBX. CONCLUSIONS. SMVL data in a prospectively defined combined analysis from these two phase 3 trials suggest a magnitude of effect of RBX on vision loss similar to that seen in two prior studies (approximately 50% reduction above standard care). However, event rates were low and statistical significance was not achieved. (ClinicalTrials.gov numbers, NCT00133952, NCT00090519.) (Invest Ophthalmol Vis Sci. 2013;54:17501757) DOI:10.1167/iovs.12-11055 C1 [Sheetz, Matthew J.; Berg, Paul H.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. [Davis, Matthew D.; Danis, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Bek, Toke] Aarhus Univ Hosp, Dept Ophthalmol, DK-8000 Aarhus, Denmark. [Cunha-Vaz, Jose] Univ Coimbra, Assoc Innovat & Biomed Res Light & Image AIBILI, Coimbra, Portugal. [Cunha-Vaz, Jose] Univ Coimbra, Fac Med, Coimbra, Portugal. [Shahri, Nazila] i3 Corp, San Diego, CA USA. RP Sheetz, MJ (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM msheetz@lilly.com FU Eli Lilly and Company, Indianapolis, Indiana; Eli Lilly and Company (Indianapolis, IN) FX Supported by Eli Lilly and Company, Indianapolis, Indiana.; The MBDL and MBCU studies were sponsored by Eli Lilly and Company (Indianapolis, IN). The authors thank the patients who participated in these studies and the physicians and investigative site staff who conducted the studies. We also thank Pamela Anderson of Eli Lilly, who was instrumental in the design and execution of the MBDL study and who provided a valuable review and critique of the manuscript. NR 18 TC 16 Z9 18 U1 0 U2 10 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2013 VL 54 IS 3 BP 1750 EP 1757 DI 10.1167/iovs.12-11055 PG 8 WC Ophthalmology SC Ophthalmology GA 117GV UT WOS:000316942400025 PM 23404115 ER PT J AU Kang, JH Wiggs, JL Pasquale, LR AF Kang, Jae H. Wiggs, Janey L. Pasquale, Louis R. TI A Nested Case Control Study of Plasma ICAM-1, E-Selectin and TNF Receptor 2 Levels, and Incident Primary Open-Angle Glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID TUMOR-NECROSIS-FACTOR; HORMONE REPLACEMENT THERAPY; OPTIC-NERVE HEAD; NORMAL-PRESSURE HYDROCEPHALUS; NORMAL-TENSION GLAUCOMA; FACTOR-ALPHA; INTRAOCULAR-PRESSURE; INSULIN-RESISTANCE; SOLUBLE RECEPTORS; MENSTRUAL-CYCLE AB PURPOSE. To evaluate prediagnostic markers of endothelial dysfunction and inflammatory processes in primary open-angle glaucoma (POAG). METHODS. Blood samples were collected from 1989 to 1990 in the Nurses' Health Study (women) and from 1993 to 1995 in the Health Professionals Follow-up Study (men), and medical-record confirmed incident POAG cases were identified (women: 229 cases and 455 controls; men: 116 cases and 228 controls). Controls were matched on cohort, age, race, ethnicity, cancer status, and date of blood collection. Plasma concentrations of ICAM-1, E-selectin, and soluble TNF receptor 2 (sTNF-R2), a marker related to TNF-alpha, were measured with ELISA assays. Cohort-specific multivariable conditional logistic regression model results were meta-analyzed. RESULTS. We observed no associations with ICAM-1 or E-selectin. For sTNF-R2, the mean (SD) plasma levels (pg/mL) in cases and controls were 2888 (997) and 2993 (913), respectively, in women; and 2622 (664) and 2569 (688), respectively, in men. Pooled multivariable results showed no relation between sTNF-R2 levels and POAG. However, compared with the lowest tertile of sTNF-R2, the highest tertile showed a significant decreased risk of POAG in women (multivariable odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.93; P-trend = 0.03) but not in men (P-trend = 0.21; P for heterogeneity by sex = 0.03). Also, among women, the inverse association with sTNF-R2 was stronger with normal-tension glaucoma (NTG; maximum intraocular pressure <21 mm Hg at diagnosis): highest versus lowest tertile comparison OR = 0.29 (95% CI = 0.12-0.71; P-trend = 0.007). CONCLUSIONS. In women, but not in men, higher sTNF-R2 levels at 6 to 8 years before diagnosis were inversely associated with POAG, but more strongly for NTG. (Invest Ophthalmol Vis Sci. 2013;54:1797-1804) DOI:10.1167/iovs.12-11191 C1 [Kang, Jae H.; Pasquale, Louis R.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Wiggs, Janey L.; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Kang, JH (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02114 USA. EM nhjhk@channing.harvard.edu FU National Institutes of Health [CA87969, CA49449, CA055075, EY09611, EY015473]; Arthur Ashley Foundation; Harvard Glaucoma Center of Excellence FX Supported by Grants CA87969, CA49449, CA055075, EY09611, and EY015473 from the National Institutes of Health and the Arthur Ashley Foundation, and the Harvard Glaucoma Center of Excellence (JLW and LRP). NR 77 TC 2 Z9 3 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2013 VL 54 IS 3 BP 1797 EP 1804 DI 10.1167/iovs.12-11191 PG 8 WC Ophthalmology SC Ophthalmology GA 117GV UT WOS:000316942400030 PM 23412091 ER PT J AU Vavvas, DG AF Vavvas, Demetrios G. TI Anti-VEGF in Retinopathy of Prematurity, Need to Titrate SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Editorial Material C1 [Vavvas, Demetrios G.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Retina Serv, Boston, MA 02114 USA. [Vavvas, Demetrios G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Vavvas, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Angiogenesis Lab, Retina Serv, Boston, MA 02114 USA. EM Vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 4 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2013 VL 54 IS 3 BP 2027 EP 2027 DI 10.1167/iovs.13-11948 PG 1 WC Ophthalmology SC Ophthalmology GA 117GV UT WOS:000316942400061 ER PT J AU Swaminathan, SS Oh, DJ Kang, MH Ren, RY Jin, R Gong, HY Rhee, DJ AF Swaminathan, Swarup S. Oh, Dong-Jin Kang, Min Hyung Ren, Ruiyi Jin, Rui Gong, Haiyan Rhee, Douglas J. TI Secreted Protein Acidic and Rich in Cysteine (SPARC)-Null Mice Exhibit More Uniform Outflow SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AQUEOUS-HUMOR OUTFLOW; OPEN-ANGLE GLAUCOMA; LOWER INTRAOCULAR-PRESSURES; HUMAN TRABECULAR MESHWORK; COLLAGEN FIBRILLOGENESIS; MORPHOLOGICAL-CHANGES; OCULAR HYPERTENSION; CATIONIC FERRITIN; GENE-EXPRESSION; BOVINE EYES AB PURPOSE. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) in many tissues and is highly expressed in trabecular meshwork (TM). SPARC-null mice have a 15% to 20% decrease in intraocular pressure (IOP) compared to wild-type (WT) mice. We hypothesized that mouse aqueous outflow is segmental, and that transgenic deletion of SPARC causes a more uniform pattern that correlates with IOP and TM morphology. METHODS. Eyes of C57BL6-SV129 WT and SPARC-null mice were injected with fluorescent microbeads, which were also passively exposed to freshly enucleated eyes. Confocal and electron microscopy were performed. Percentage effective filtration length (PEFL) was calculated as PEFL = FL/TL x 100%, where TL = total length and FL filtration length. IOP was measured by rebound tonometry. RESULTS. Passive microbead affinity for WT and SPARC-null ECM did not differ. Segmental flow was observed in the mouse eye. SPARC-null mice had a 23% decrease in IOP. PEFL increased in SPARC-null (70.61 +/- 11.36%) versus WT mice (54.68 +/- 9.95%, P < 0.005; n = 11 pairs), and PEFL and IOP were negatively correlated (R-2 = 0.72, n = 10 pairs). Morphologically, TM of high-tracer regions had increased separation between beams compared to low-tracer regions. Collagen fibril diameter decreased in SPARC-null (28.272 nm) versus WT tissue (34.961 nm, P < 0.0005; n = 3 pairs). CONCLUSIONS. Aqueous outflow in mice is segmental. SPARC-null mice demonstrated a more uniform outflow pattern and decreased collagen fibril diameter. Areas of high flow had less compact juxtacanalicular connective tissue ECM, and IOP was inversely correlated with PEFL. Our data show a correlation between morphology, aqueous outflow, and IOP, indicating a modulatory role of SPARC in IOP regulation. (Invest Ophthalmol Vis Sci. 2013; 54: 2035-2047) DOI: 10.1167/iovs.12-10950 C1 [Swaminathan, Swarup S.; Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Ren, Ruiyi; Jin, Rui; Gong, Haiyan] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com OI Gong, Haiyan/0000-0002-7204-5019 FU National Eye Institute [EY019654-01, EY14104, EY018712, EY022634]; Harvard-MIT Division of Health Sciences and Technology Research Assistantship Program; Howard Hughes Medical Institute Medical Research Fellowship; Massachusetts Lions Research Fund FX Supported by National Eye Institute EY019654-01 (DJR), EY14104 (MEEI Vision-Core Grant), EY018712 (HG), and EY022634 (HG); Harvard-MIT Division of Health Sciences and Technology Research Assistantship Program (SSS); Howard Hughes Medical Institute Medical Research Fellowship (SSS); and the Massachusetts Lions Research Fund. NR 50 TC 30 Z9 32 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2013 VL 54 IS 3 BP 2035 EP 2047 DI 10.1167/iovs.12-10950 PG 13 WC Ophthalmology SC Ophthalmology GA 117GV UT WOS:000316942400063 PM 23422826 ER PT J AU Walker, LC Diamond, MI Duff, KE Hyman, BT AF Walker, Lary C. Diamond, Marc I. Duff, Karen E. Hyman, Bradley T. TI Mechanisms of Protein Seeding in Neurodegenerative Diseases SO JAMA NEUROLOGY LA English DT Review ID ALZHEIMERS-DISEASE; ENTORHINAL CORTEX; MOUSE MODEL; TAU; PROPAGATION; TAUOPATHY; PATHOLOGY; BRAIN; NEURONS; MEMORY AB Most age-associated neurodegenerative diseases involve the aggregation of specific proteins within the nervous system. In Alzheimer disease, the insidious pathogenic process begins many years before the symptoms emerge, and the lesions that characterize the disease-senile plaques and neurofibrillary tangles-ramify systematically through the brain. We review evidence that the beta-amyloid and tau proteins, which aggregate to form senile plaques and neurofibrillary tangles, respectively, are induced to misfold and self-assemble by a process of templated conformational change that amplifies a toxic species. Recent data also indicate that the spread of these lesions from one site to another is mediated by the cellular uptake, transport, and release of endogenous seeds formed by the cognate proteins. This simple pathogenic principle suggests that the formation, trafficking, and metabolism of pathogenic protein seeds are promising therapeutic targets for Alzheimer disease and other neurodegenerative disorders. JAMA Neurol. 2013; 70(3):304-310. Published online December 10, 2012. doi:10.1001/jamaneurol.2013.1453 C1 [Walker, Lary C.] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Neurol, Atlanta, GA 30329 USA. [Diamond, Marc I.] Washington Univ, Dept Neurol, St Louis Sch Med, St Louis, MO USA. [Duff, Karen E.] Columbia Univ, Dept Pathol & Cell Biol, Taub Inst Alzheimers Dis Res, New York, NY USA. [Duff, Karen E.] New York State Psychiat Inst & Hosp, Dept Psychiat, New York, NY 10032 USA. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol,Massachusetts Gen Hosp, Alzheimers Dis Res Lab,MassGen Inst Neurodegenera, Boston, MA 02115 USA. RP Walker, LC (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Dept Neurol, 954 Gatewood Rd NE, Atlanta, GA 30329 USA. EM lary.walker@emory.edu RI Walker, L/J-6541-2015 OI Walker, L/0000-0001-9166-3261 FU National Institutes of Health [R21AG040589, P51RR165, P51OD11132, P01AG005119, R01NS071835, 1F31NS079039, R01NS074874, R21AG038835-01A1, R21NS067127]; CART Foundation; Muscular Dystrophy Association; Tau Consortium; American Health Assistance Foundation FX Dr Hyman has stock options with Novartis and consults or has sponsored research agreements for Pfizer, Neurophage, Neotope, Biogen, GlaxoSmithKline, Siemens, Elan, Accumen, and Takeda, none of which were involved in these projects.; This work was supported by grants R21AG040589, P51RR165, P51OD11132, and P01AG005119 (Dr Walker), R01NS071835 (Dr Diamond), 1F31NS079039 and R01NS074874 (Dr Duff), and R21AG038835-01A1 and R21NS067127 (Dr Hyman) from the National Institutes of Health, by grants from the CART Foundation (Dr Walker), Muscular Dystrophy Association (Dr Diamond), Tau Consortium (Dr Diamond), and American Health Assistance Foundation (Drs Diamond and Hyman), and by a postdoctoral fellowship from the American Health Assistance Foundation (Dr Duff's laboratory). NR 33 TC 76 Z9 79 U1 1 U2 50 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD MAR PY 2013 VL 70 IS 3 BP 304 EP 310 DI 10.1001/jamaneurol.2013.1453 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 115HY UT WOS:000316804400003 PM 23599928 ER PT J AU Callahan, AB Rizzo, JF AF Callahan, Alison B. Rizzo, Joseph F. TI Twenty-four-Year-Old Woman With a Droopy Eyelid SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID HORNER SYNDROME C1 [Callahan, Alison B.; Rizzo, Joseph F.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Callahan, AB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM alison_callahan@meei.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAR PY 2013 VL 131 IS 3 BP 401 EP 402 PG 2 WC Ophthalmology SC Ophthalmology GA 113SD UT WOS:000316687600022 PM 23494047 ER PT J AU Guha, S Rees, E Darvasi, A Ivanov, D Ikeda, M Bergen, SE Magnusson, PK Cormican, P Morris, D Gill, M Cichon, S Rosenfeld, JA Lee, A Gregersen, PK Kane, JM Malhotra, AK Rietschel, M Nothen, MM Degenhardt, F Priebe, L Breuer, R Strohmaier, J Ruderfer, DM Moran, JL Chambert, KD Sanders, AR Shi, JX Kendler, K Riley, B O'Neill, T Walsh, D Malhotra, D Corvin, A Purcell, S Sklar, P Iwata, N Hultman, CM Sullivan, PF Sebat, J McCarthy, S Gejman, PV Levinson, DF Owen, MJ O'Donovan, MC Lencz, T Kirov, G AF Guha, Saurav Rees, Elliott Darvasi, Ariel Ivanov, Dobril Ikeda, Masashi Bergen, Sarah E. Magnusson, Patrik K. Cormican, Paul Morris, Derek Gill, Michael Cichon, Sven Rosenfeld, Jeffrey A. Lee, Annette Gregersen, Peter K. Kane, John M. Malhotra, Anil K. Rietschel, Marcella Noethen, Markus M. Degenhardt, Franziska Priebe, Lutz Breuer, Rene Strohmaier, Jana Ruderfer, Douglas M. Moran, Jennifer L. Chambert, Kimberly D. Sanders, Alan R. Shi, Jianxin Kendler, Kenneth Riley, Brien O'Neill, Tony Walsh, Dermot Malhotra, Dheeraj Corvin, Aiden Purcell, Shaun Sklar, Pamela Iwata, Nakao Hultman, Christina M. Sullivan, Patrick F. Sebat, Jonathan McCarthy, Shane Gejman, Pablo V. Levinson, Douglas F. Owen, Michael J. O'Donovan, Michael C. Lencz, Todd Kirov, George CA Mol Genetics Schizophrenia Wellcome Trust Case Control TI Implication of a Rare Deletion at Distal 16p11.2 in Schizophrenia SO JAMA PSYCHIATRY LA English DT Article ID COPY-NUMBER VARIATION; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; DE-NOVO; DEVELOPMENTAL DELAY; DISEASE; GENE; POPULATION; MUTATIONS; PHENOTYPE AB Context: Large genomic copy number variations have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication. Objective: To detect novel copy number variations that increase the susceptibility to schizophrenia by using 2 ethnically homogeneous discovery cohorts and replication in large samples. Design: Genetic association study of microarray data. Setting: Samples of DNA were collected at 9 sites from different countries. Participants: Two discovery cohorts consisted of 790 cases with schizophrenia and schizoaffective disorder and 1347 controls of Ashkenazi Jewish descent and 662 parent-offspring trios from Bulgaria, of which the offspring had schizophrenia or schizoaffective disorder. Replication data sets consisted of 12 398 cases and 17 945 controls. Main Outcome Measures: Statistically increased rate of specific copy number variations in cases vs controls. Results: One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 of 13 850 cases (0.094%) and 3 of 19 954 controls (0.015%) (odds ratio, 6.25 [95% CI, 1.78-21.93]; P=.001, Fisher exact test). Conclusions: Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains 9 genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional 8 genes. Our findings add a new locus to the list of copy number variations that increase the risk for development of schizophrenia. JAMA Psychiatry. 2013; 70(3): 253-260. Published online January 16, 2013. doi:10.1001/2013.jamapsychiatry.71 C1 [Guha, Saurav; Kane, John M.; Malhotra, Anil K.; Lencz, Todd] Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA. [Rees, Elliott; Ivanov, Dobril; Owen, Michael J.; O'Donovan, Michael C.; Kirov, George] Cardiff Univ, Med Res Council, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Rees, Elliott; Ivanov, Dobril; Owen, Michael J.; O'Donovan, Michael C.; Kirov, George] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF10 3AX, S Glam, Wales. [Darvasi, Ariel] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Ikeda, Masashi; Iwata, Nakao] Fujita Hlth Univ, Sch Med, Toyoake, Aichi 47011, Japan. [Bergen, Sarah E.; Purcell, Shaun] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Bergen, Sarah E.; Purcell, Shaun] Harvard Univ, Sch Med, Boston, MA USA. [Bergen, Sarah E.; Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Bergen, Sarah E.; Moran, Jennifer L.; Chambert, Kimberly D.; Purcell, Shaun] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Magnusson, Patrik K.; Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Cormican, Paul; Morris, Derek; Gill, Michael; Corvin, Aiden] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland. [Walsh, Dermot] Hlth Res Board, Dublin, Ireland. [Cichon, Sven; Noethen, Markus M.; Degenhardt, Franziska; Priebe, Lutz] Univ Bonn, Inst Human Genet, Bonn, Germany. [Cichon, Sven; Degenhardt, Franziska; Priebe, Lutz] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Noethen, Markus M.] Ctr Neurodegenerat Dis, Bonn, Germany. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med, Julich, Germany. [Rosenfeld, Jeffrey A.] Univ Med & Dent New Jersey, IST High Performance & Res Comp, Newark, NJ 07103 USA. [Lee, Annette; Gregersen, Peter K.] Feinstein Inst Med Res, Robert S Boas Ctr Human Genet & Genom, Manhasset, NY USA. [Kane, John M.; Malhotra, Anil K.; Lencz, Todd] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Kane, John M.; Malhotra, Anil K.; Lencz, Todd] Hofstra Univ, Sch Med, Dept Psychiat, Long Isl City, NY USA. [Rietschel, Marcella; Breuer, Rene; Strohmaier, Jana] Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Mannheim, Germany. [Ruderfer, Douglas M.; Purcell, Shaun; Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. [Sanders, Alan R.; Gejman, Pablo V.] NorthShore Univ, HealthSyst Res Inst, Dept Psychiat & Behav Sci, Evanston, IL USA. [Sanders, Alan R.; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA. [Shi, Jianxin] NCI, Bethesda, MD 20892 USA. [Kendler, Kenneth] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. [Riley, Brien] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23284 USA. [O'Neill, Tony] Queens Univ, Dept Psychiat, Belfast, Ireland. [Malhotra, Dheeraj; Sebat, Jonathan] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA 92093 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [McCarthy, Shane] Woodbury Genome Ctr, Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring on Hudson, NY USA. [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Lencz, T (reprint author), Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd st, Glen Oaks, NY 11004 USA. EM tlencz@NSHS.edu; Kirov@cardiff.ac.uk RI Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Ruderfer, Douglas/M-5795-2016; Lencz, Todd/J-3418-2014; Magnusson, Patrik/C-4458-2017; OI Gill, Michael/0000-0003-0206-5337; Ivanov, Dobril/0000-0001-6271-6301; Moran, Jennifer/0000-0002-5664-4716; Nothen, Markus/0000-0002-8770-2464; Cichon, Sven/0000-0002-9475-086X; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Guha, Saurav/0000-0002-0620-5408; Morris, Derek/0000-0002-3413-570X; Cichon, Sven/0000-0002-9475-086X; Ruderfer, Douglas/0000-0002-2365-386X; Lencz, Todd/0000-0001-8586-338X; Bergen, Sarah/0000-0002-5888-0034; Sebat, Jonathan/0000-0002-9087-526X FU Medical Research Council [G0800509]; National Institute of Mental Health (NIMH) [2 P50 MH066392-05A1]; EU-GEI from the European Union; Stanley Medical Research Institute; Merck Genome Research Foundation; Herman Foundation; North Shore-Long Island Jewish Health System Foundation; National Institutes of Health [RC2 MH089964, R01 MH084098, P50 MH080173, P30 MH090590]; NIMH [MH67257, H59588, MH59571, MH59565, MH59587, MH60870, MH59566, MH59586, MH61675, MH60879, MH81800, MH46276, MH46289, MH46318, MH79469, MH79470]; National Alliance for Research on Schizophrenia and Depression; Genetic Association Information Network; Paul Michael Donovan Charitable Foundation; Walter E. Nichols, MD, and Eleanor Nichols endowments (Stanford University); National Center for Research Resources [U54 RR020278]; German Federal Ministry of Education and Research (BMBF) [01GS08144, 01GS08147]; Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z, 068545/Z/02]; UK Medical Research Council [G0000934]; UK National Blood Service; Japan Ministry of Education, Culture, Sports, Science and Technology; Ministry of Health, Labor and Welfare; Core Research for Evolutional Science and Technology; Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation) FX Work at Cardiff University was supported by grant G0800509 from the Medical Research Council Programme and Centre Grants, grant 2 P50 MH066392-05A1 from the National Institute of Mental Health (NIMH), and grant EU-GEI from the European Union. Genotyping was funded by multiple grants to the Stanley Center for Psychiatric Research at the Broad Institute from the Stanley Medical Research Institute, the Merck Genome Research Foundation, and the Herman Foundation. The Zucker Hillside Hospital work was supported by the North Shore-Long Island Jewish Health System Foundation and grants RC2 MH089964 (Dr Lencz), R01 MH084098 (Dr Lencz), P50 MH080173 (Dr A. K. Malhotra), and P30 MH090590 (Dr Kane) from the National Institutes of Health. Molecular Genetics of Schizophrenia Consortium data collection was supported by R01 grants MH67257, H59588, MH59571, MH59565, MH59587, MH60870, MH59566, MH59586, MH61675, MH60879, and MH81800 and U01 grants MH46276, MH46289, MH46318, MH79469, and MH79470 from the NIMH. We acknowledge support through Young Investigator Awards (Dr Sanders and Jubao Duan, PhD) from the National Alliance for Research on Schizophrenia and Depression and from the Genetic Association Information Network, the Paul Michael Donovan Charitable Foundation, and the Walter E. Nichols, MD, and Eleanor Nichols endowments (Stanford University). Genotyping performed by the Center for Genotyping and Analysis at the Broad Institute of Harvard and Massachusetts Institute of Technology was supported by grant U54 RR020278 from the National Center for Research Resources. The German study was supported by grants 01GS08144 and 01GS08147 from the German Federal Ministry of Education and Research (BMBF), within the context of the Integrated Genome Research Network MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia). Control data were provided by the community-based studies of PopGen (Population-based Recruitment of Patients and Controls for the Analysis of Complex Genotype-Phenotype Relationships), Cooperative Health Research in the Region Augsburg, the Heinz Nixdorf Recall study, and MooDS. Genotyping of Wellcome Trust Case Control Consortium 2 samples was funded by grants 085475/B/08/Z and 085475/Z/08/Z from the Wellcome Trust. The British 1958 Birth Cohort DNA collection was funded by grant G0000934 from the UK Medical Research Council and grant 068545/Z/02 from the Wellcome Trust, and the UK National Blood Service controls by the Wellcome Trust. The Japanese cohort was supported in part by research grants from the Japan Ministry of Education, Culture, Sports, Science and Technology; the Ministry of Health, Labor and Welfare; the Core Research for Evolutional Science and Technology; and the Health Sciences Foundation (Research on Health Sciences focusing on Drug Innovation). NR 28 TC 23 Z9 23 U1 2 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-622X J9 JAMA PSYCHIAT JI JAMA Psychiatry PD MAR PY 2013 VL 70 IS 3 BP 253 EP 260 DI 10.1001/2013.jamapsychiatry.71 PG 8 WC Psychiatry SC Psychiatry GA 114GY UT WOS:000316730300002 PM 23325106 ER PT J AU Bergman, J Brook, RH Litwin, MS AF Bergman, Jonathan Brook, Robert H. Litwin, Mark S. TI A Call to Action Improving Value by Emphasizing Patient-Centered Care at the End of Life SO JAMA SURGERY LA English DT Editorial Material C1 [Bergman, Jonathan; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Bergman, Jonathan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bergman, Jonathan] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. [Brook, Robert H.] RAND Corp, Santa Monica, CA USA. RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, POB 951738, Los Angeles, CA 90095 USA. EM jbergman@mednet.ucla.edu NR 8 TC 3 Z9 3 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 J9 JAMA SURG JI JAMA Surg. PD MAR PY 2013 VL 148 IS 3 BP 215 EP 216 PG 2 WC Surgery SC Surgery GA 113QG UT WOS:000316682000001 PM 23552885 ER PT J AU Coskun, S Otu, HH Awartani, KA Al-Alwan, LA Al-Hassan, S Al-Mayman, H Kaya, N Inan, MS AF Coskun, Serdar Otu, Hasan H. Awartani, Khalid A. Al-Alwan, Laila A. Al-Hassan, Saad Al-Mayman, Hend Kaya, Namik Inan, Mehmet S. TI Gene expression profiling of granulosa cells from PCOS patients following varying doses of human chorionic gonadotropin SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Granulosa cells; Gene expression; hCG; Microarray/PCOS ID POLYCYSTIC-OVARY-SYNDROME; HUMAN CUMULUS CELLS; FOLLICLE-STIMULATING-HORMONE; IN-VITRO FERTILIZATION; FSH RECEPTOR; MICROARRAY ANALYSIS; OVULATORY FOLLICLE; OOCYTE MATURATION; ANTRAL FOLLICLES; RECOMBINANT FSH AB Human chorionic gonadotrophin (hCG) has been used to induce ovulation and oocyte maturation. Although the most common dose of hCG used in IVF is 10,000 IU, there are reports that suggest 5,000 IU is sufficient to yield similar results. The objective of this study is to evaluate the dose dependent differences in gene expression of granulosa cells following various doses of hCG treatment. Patients with polycystic ovarian syndrome (PCOS) were stimulated for IVF treatment. The hCG injection was either withheld or given at 5,000 or 10,000 IU. Granulosa cells from the follicular fluids have been collected for RNA isolation and analyzed using Affymetrix genechip arrays. Unsupervised hierarchical clustering based on whole gene expression revealed two distinct groups of patients in this experiment. All untreated patients were clustered together whereas hCG-treated patients separated to a different group regardless of the dose. A large number of the transcripts were similarly up- or down-regulated across both hCG doses (2229 and 1945 transcripts, respectively). However, we observed dose-dependent statistically significant differences in gene expression in only 15 transcripts. Although hCG injection caused a major change in the gene expression profile of granulosa cells, 10,000 IU hCG resulted in minimal changes in the gene expression profiles of granulosa cells as compared with 5,000 IU. Thus, based on our results, we suggest the use of 10,000 IU hCG should be reconsidered in PCOS patients. C1 [Coskun, Serdar; Al-Mayman, Hend] King Faisal Specialist Hosp & Res Ctr, Dept Pathol & Lab Med, Riyadh 11211, Saudi Arabia. [Otu, Hasan H.] Harvard Univ, Sch Med, Dept Med, BIDMC Genom Ctr, Boston, MA 02115 USA. [Otu, Hasan H.] Istanbul Bilgi Univ, Dept Genet & Bioengn, TR-34060 Istanbul, Turkey. [Awartani, Khalid A.; Al-Hassan, Saad] King Faisal Specialist Hosp & Res Ctr, Dept Obstet & Gynecol, Riyadh 11211, Saudi Arabia. [Al-Alwan, Laila A.; Kaya, Namik; Inan, Mehmet S.] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. RP Coskun, S (reprint author), King Faisal Specialist Hosp & Res Ctr, Dept Pathol & Lab Med, Riyadh 11211, Saudi Arabia. EM serdar@kfshrc.edu.sa OI Otu, Hasan/0000-0002-9253-8152 NR 46 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD MAR PY 2013 VL 30 IS 3 BP 341 EP 352 DI 10.1007/s10815-013-9935-y PG 12 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 114PC UT WOS:000316753300007 PM 23381551 ER PT J AU Friedstat, JS Moore, ME Goverman, J Fagan, SP AF Friedstat, Jonathan S. Moore, Molly E. Goverman, Jeremy Fagan, Shawn P. TI An Unusual Burn During Routine Magnetic Resonance Imaging SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID PATIENT AB Burn injuries are known to occur from magnetic resonance imaging. Prevention efforts focus on avoiding internal and external metallic objects from contacting the patient's tissue during image acquisition. Despite rigorous screening, however, there is a subset of thermal injuries that can occur through the formation of closed loops of current within the patient. This case report describes an example of this uncommon type of injury as well as a successful, nonoperative management approach. Given the frequent use of magnetic resonance imaging, we report this rare case to raise awareness of this mechanism of injury and its treatment. (J Burn Care Res 2013;34:e110-e111) C1 [Friedstat, Jonathan S.; Moore, Molly E.; Goverman, Jeremy; Fagan, Shawn P.] Massachusetts Gen Hosp, Dept Surg, Div Burns, Boston, MA 02114 USA. RP Fagan, SP (reprint author), 55 Fruit St,GRB 1303, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2013 VL 34 IS 2 BP E110 EP E111 DI 10.1097/BCR.0b013e3182642a40 PG 2 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 117GR UT WOS:000316942000007 PM 23128132 ER PT J AU Fuzaylov, G Driscoll, DN Volfson, I AF Fuzaylov, Gennadiy Driscoll, Daniel N. Volfson, Inna TI A Plan to Improve Pediatric Burn Care in Ukraine SO JOURNAL OF BURN CARE & RESEARCH LA English DT Letter C1 [Fuzaylov, Gennadiy] Harvard Univ, Massachusetts Gen Hosp, Shriners Hosp Burn Children,Med Sch, Dept Anesthesia Crit Care & Pain Med,Doctors Coll, Boston, MA 02115 USA. [Driscoll, Daniel N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Volfson, Inna] Doctors Collaborating Help Children, Wayland, MA USA. RP Fuzaylov, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shriners Hosp Burn Children,Med Sch, Dept Anesthesia Crit Care & Pain Med,Doctors Coll, 55 Fruit St,Gray Jackson 409, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2013 VL 34 IS 2 BP E119 EP E120 DI 10.1097/BCR.0b013e318267c942 PG 2 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 117GR UT WOS:000316942000011 PM 23202873 ER PT J AU Leaf, DE Pereira, RC Bazari, H Juppner, H AF Leaf, David E. Pereira, Renata C. Bazari, Hasan Jueppner, Harald TI Oncogenic Osteomalacia due to FGF23-Expressing Colon Adenocarcinoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INAPPROPRIATE ANTIDIURETIC-HORMONE; SMALL-CELL-CARCINOMA; PROSTATE-CANCER; COLORECTAL-CANCER; VITAMIN-D; K-RAS; HYPOPHOSPHATEMIA; MUTATIONS; RECEPTOR; FGF23 AB Context: Oncogenic osteomalacia, a paraneoplastic syndrome associated with hypophosphatemia due to increased urinary phosphate excretion, is caused by excessive synthesis and secretion of fibroblast growth factor 23 (FGF23), a phosphaturic hormone that is normally produced by osteocytes. Most cases of oncogenic osteomalacia have been associated with benign tumors of bone or soft tissue; however, whether malignant neoplasms can also produce and secrete FGF23 is currently unknown. Objective: The aim was to determine whether a malignant neoplasm could cause oncogenic osteomalacia through excessive production and secretion of FGF23. Setting: We describe an 80-year-old woman with stage IV colon adenocarcinoma who presented with severe hypophosphatemia (0.4 mg/dL; reference, 2.6-4.5 mg/dL). Results: Fractional excretion of phosphate was 34% (reference, <5% in the setting of hypophosphatemia), and plasma levels of FGF23 were highly elevated at 674 RU/mL (reference, <180 RU/mL). Immunohistochemical analysis of the patient's tumor showed strong staining for FGF23. Genetic analyses revealed a point mutation in the KRAS gene. Conclusions: We present the first case in which a malignant neoplasm is documented to produce and secrete FGF23, leading to renal phosphate-wasting. Oncogenic osteomalacia should be considered in the differential diagnosis for patients with a malignant tumor who present with hypophosphatemia. (J Clin Endocrinol Metab 98: 887-891, 2013) C1 [Leaf, David E.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Pereira, Renata C.] Univ Calif Los Angeles, Div Pediat Nephrol, Los Angeles, CA 90095 USA. [Leaf, David E.; Bazari, Hasan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Leaf, DE (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02115 USA. EM DELEAF@partners.org FU National Institutes of Health [PO DK11794] FX This work was supported in part by the National Institutes of Health (PO1 DK11794). NR 25 TC 18 Z9 19 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2013 VL 98 IS 3 BP 887 EP 891 DI 10.1210/jc.2012-3473 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 110BN UT WOS:000316417200032 PM 23393166 ER PT J AU Fazeli, PK Horowitz, MC MacDougald, OA Scheller, EL Rodeheffer, MS Rosen, CJ Klibanski, A AF Fazeli, Pouneh K. Horowitz, Mark C. MacDougald, Ormond A. Scheller, Erica L. Rodeheffer, Matthew S. Rosen, Clifford J. Klibanski, Anne TI Marrow Fat and Bone-New Perspectives SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID PROTON MR SPECTROSCOPY; SYMPATHETIC-NERVOUS-SYSTEM; TRANSCRIPTION FACTOR EBF; MESENCHYMAL STEM-CELLS; PREADIPOCYTE FACTOR-I; MINERAL DENSITY; ADIPOSE-TISSUE; ANOREXIA-NERVOSA; GROWTH-HORMONE; PROGENITOR CELLS AB Context: There is growing interest in the relationship between bone mineral density, bone strength, and fat depots. Marrow adipose tissue, a well-established component of the marrow environment, is metabolically distinct from peripheral fat depots, but its functional significance is unknown. Objective: In this review, we discuss animal and human data linking the marrow adipose tissue depot to parameters of bone density and integrity as well as the potential significance of marrow adipose tissue in metabolic diseases associated with bone loss, including type 1 diabetes mellitus and anorexia nervosa. Potential hormonal determinants of marrow adipose tissue are also discussed. Conclusions: We conclude that whereas most animal and human data demonstrate an inverse association between marrow adipose tissue and measures of bone density and strength, understanding the functional significance of marrow adipose tissue and its hormonal determinants will becritical to better understanding its role in skeletal integrityandthe role of marrow adipose tissue in the pathophysiology of bone loss. (J Clin Endocrinol Metab 98: 935-945, 2013) C1 [Fazeli, Pouneh K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Fazeli, Pouneh K.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Horowitz, Mark C.] Yale Univ, Sch Med, Dept Orthoped & Rehabil, New Haven, CT 06520 USA. [MacDougald, Ormond A.; Scheller, Erica L.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48105 USA. [MacDougald, Ormond A.; Scheller, Erica L.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48105 USA. [Rodeheffer, Matthew S.] Yale Univ, Sch Med, Comparat Med Sect, New Haven, CT 06520 USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org OI MacDougald, Ormond/0000-0001-6907-7960; Scheller, Erica/0000-0002-1551-3816 FU National Institute of Diabetes, Digestive and Kidney Diseases/National Institutes of Health [R24DK092759, K23 DK094820]; Yale Core Center for Musculoskeletal Disorders [P30AR046032]; Departmentof Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven FX Writing of this review and experimental work were enabled by support from the National Institute of Diabetes, Digestive and Kidney Diseases/National Institutes of Health (Grants R24DK092759 and K23 DK094820 to P.K.F.), the Yale Core Center for Musculoskeletal Disorders(GrantP30AR046032), and the Departmentof Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut (to M.C.H.). NR 105 TC 83 Z9 83 U1 4 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2013 VL 98 IS 3 BP 935 EP 945 DI 10.1210/jc.2012-3634 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 110BN UT WOS:000316417200037 PM 23393168 ER PT J AU Roth, MY Nya-Ngatchou, JJS Lin, K Page, ST Anawalt, BD Matsumoto, AM Marck, BT Bremner, WJ Amory, JK AF Roth, M. Y. Nya-Ngatchou, J. J. S. Lin, K. Page, S. T. Anawalt, B. D. Matsumoto, A. M. Marck, B. T. Bremner, W. J. Amory, J. K. TI Androgen Synthesis in the Gonadotropin-Suppressed Human Testes Can Be Markedly Suppressed by Ketoconazole SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INTRATESTICULAR STEROID-LEVELS; HUMAN CHORIONIC-GONADOTROPIN; NORMAL MEN; NONOBSTRUCTIVE AZOOSPERMIA; TESTOSTERONE ENANTHATE; CONTRACEPTIVE EFFICACY; HORMONE ANTAGONIST; DOSE KETOCONAZOLE; MALE-INFERTILITY; YOUNG MEN AB Context: The concentration of intratesticular testosterone (IT-T) required for human spermatogenesis is unknown because spermatogenesis can persist despite the markedly reduced IT-T concentrations observed with LH suppression. Methods to lower IT-T further are needed to determine the relationship between IT-T and spermatogenesis. Objective: The objective of the study was to determine the effect of inhibiting the synthesis and metabolism of testosterone (T) on IT-T in gonadotropin-suppressed human testes. Design/Setting/Patients: Forty normal men participated in a blinded, placebo-controlled, randomized trial at an academic center. Intervention/Outcome Measures: All men were first administered the GnRH antagonist acyline to suppress LH. Forty-eight hours after acyline administration, subjects were randomly assigned to placebo, ketoconazole (to inhibit T synthesis) at 400 or 800 mg, dutasteride (to inhibit T metabolism) 2.5 mg, or anastrazole (to inhibit T metabolism) 1 mg, daily for 7 days (n = 8/group). Intratesticular steroid concentrations were measured 48 hours after acyline administration alone and again after 7 days of combination treatment. Results: After 7 days of combination treatment, the median IT-T (25th, 75th percentile) in the placebo group was 14 (8.0, 21.2) ng/mL. IT-T was reduced to 3.7 (2.5, 7.1) ng/mL in the ketoconazole 400 mg group and 1.7 (0.8, 4.0) ng/mL in the ketoconazole 800 mg group (P < .001 vs placebo for both comparisons). IT-T concentrations in the dutasteride and anastrazole groups were similar to placebo. Conclusion: Combining inhibition of steroidogenesis with gonadotropin suppression lowers IT-T more than gonadotropin suppression alone. This combination might be useful to determine the minimum IT-T concentration necessary for human spermatogenesis, information essential for developing male hormonal contraceptives. (J Clin Endocrinol Metab 98: 1198-1206, 2013) C1 [Roth, M. Y.; Nya-Ngatchou, J. J. S.; Page, S. T.; Anawalt, B. D.; Matsumoto, A. M.; Bremner, W. J.; Amory, J. K.] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. [Lin, K.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Roth, M. Y.; Nya-Ngatchou, J. J. S.; Page, S. T.; Anawalt, B. D.; Matsumoto, A. M.; Bremner, W. J.; Amory, J. K.] Univ Washington, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. [Matsumoto, A. M.; Marck, B. T.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Roth, MY (reprint author), Univ Washington, 1959 NE Pacific St,Box 357138, Seattle, WA 98195 USA. EM mylang@u.washington.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development as part of the Cooperative Contraceptive Research Centers Program [U54 HD-42454]; Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant [K12 HD053984]; National Institute of Diabetes and Digestive and Kidney Diseases [5T32 DK007247-35]; Department of Veterans Affairs FX This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through Cooperative Agreement U54 HD-42454 as part of the Cooperative Contraceptive Research Centers Program. M.Y.R. is supported, in part, by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant K12 HD053984. J.J.S.N. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases training grant 5T32 DK007247-35. A.M.M. is supported by the Department of Veterans Affairs. NR 30 TC 4 Z9 4 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2013 VL 98 IS 3 BP 1198 EP 1206 DI 10.1210/jc.2012-3527 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 110BN UT WOS:000316417200071 PM 23348398 ER PT J AU Bourne, SK Walcott, BP Sheth, SA Coumans, JVCE AF Bourne, Sarah K. Walcott, Brian P. Sheth, Sameer A. Coumans, Jean-Valery C. E. TI Neurological surgery: The influence of physical and mental demands on humans performing complex operations SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Review DE Neurosurgery; Work hours; Endurance; Ergonomics; Error; Fatigue; Music ID AGGRESSIVE MICROSURGICAL RESECTION; WEEKEND HOSPITAL ADMISSION; POSTERIOR SPINAL-FUSION; TERM-FOLLOW-UP; SLEEP-DEPRIVATION; AMERICAN SURGEONS; MEDICAL ERRORS; NEUROMUSCULAR SCOLIOSIS; ACCREDITATION COUNCIL; PSYCHOLOGICAL STRESS AB Performing neurological surgery is an inherently demanding task on the human body, both physically and mentally. Neurosurgeons routinely perform "high stakes" operations in the setting of mental and physical fatigue. These conditions may be not only the result of demanding operations, but also influential to their outcome. Similar to other performance-based endurance activities, training is paramount to successful outcomes. The inflection point, where training reaches the point of diminishing returns, is intensely debated. For the neurosurgeon, this point must be exploited to the maximum, as patients require both the best-trained and best-performing surgeon. In this review, we explore the delicate balance of training and performance, as well as some routinely used adjuncts to improve human performance. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Bourne, Sarah K.; Walcott, Brian P.; Sheth, Sameer A.; Coumans, Jean-Valery C. E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Bourne, Sarah K.; Walcott, Brian P.; Sheth, Sameer A.; Coumans, Jean-Valery C. E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 102 TC 4 Z9 5 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD MAR PY 2013 VL 20 IS 3 BP 342 EP 348 DI 10.1016/j.jocn.2012.09.008 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 115VL UT WOS:000316839900002 PM 23394875 ER PT J AU Stange, JP Sylvia, LG Magalhaes, PVD Miklowitz, DJ Otto, MW Frank, E Berk, M Nierenberg, AA Deckersbach, T AF Stange, Jonathan P. Sylvia, Louisa G. da Silva Magalhaes, Pedro Vieira Miklowitz, David J. Otto, Michael W. Frank, Ellen Berk, Michael Nierenberg, Andrew A. Deckersbach, Thilo TI Extreme Attributions Predict the Course of Bipolar Depression: Results From the STEP-BD Randomized Controlled Trial of Psychosocial Treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; FAMILY-FOCUSED TREATMENT; SOCIAL RHYTHM THERAPY; COGNITIVE THERAPY; MOOD DISORDERS; RELAPSE PREVENTION; ANXIETY DISORDERS; RESPONSE STYLE; CLINICAL-TRIAL; LIFE EVENTS AB Objective: Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study, we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression. Method: 106 depressed outpatients with DSM-IV bipolar I or II disorder who were enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder were randomly assigned to intensive psychotherapy for depression (n=62) or to collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005. Results: All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (P<.01; OR=0.93; 95% CI, 0.88-0.98) and longer time until recovery (P<.01; OR = 0.96; 95% CI, 0.93-0.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, higher initial depression severity predicted a lower likelihood of recovery (P=.01; OR=0.64; 95% CI, 0.45-0.91) and longer time until recovery (P<.001; OR=0.76; 95% CI, 0.66-0.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90; 95% CI, 0.40-2.01) in the full sample. Conclusions:These results suggest that extreme, rigid attributions may be associated with a more severe course of depression and that evaluating attributional style may help clinicians to identify patients who are at risk for experiencing a more severe course of depression. Trial Registration: ClinicalTrials.gov identifier: NCT00012558 J Clin Psychiatry 2013;74(3):249-255 (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Stange, Jonathan P.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Sylvia, Louisa G.; Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sylvia, Louisa G.; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA. [da Silva Magalhaes, Pedro Vieira] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil. [Miklowitz, David J.] Univ Calif Los Angeles, Sch Med, Div Child & Adolescent Psychiat, Los Angeles, CA USA. [Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Frank, Ellen] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Berk, Michael] Deakin Univ, Sch Med, Geelong, Vic 3217, Australia. [Berk, Michael] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Orygen Youth Hlth Res Ctr, Ctr Youth Mental Hlth, Parkville, Vic 3052, Australia. [Berk, Michael] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, 50 Staniford St,5th Fl, Boston, MA 02114 USA. EM tdeckersbach@partners.org RI Magalhaes, Pedro/A-8519-2008; Berk, Michael/M-7891-2013 OI Magalhaes, Pedro/0000-0002-5644-6357; Berk, Michael/0000-0002-5554-6946 FU National Institute of Mental Health (NIMH); New Harbinger Publishers; NIMH; Brain and Behavior Research Foundation; Danny Alberts Foundation; Attias Family Foundation; Guilford Press and John Wiley and Sons; Guilford Press; American Psychological Association Press; National Institutes of Health; National Health and Medical Research Council; CRC Simons; Allen Unwin; Cambridge University Press; American Society of Clinical Psychopharmacology; Australasian Society for Bipolar Disorder; Bayamon Region Psychiatric Society; Belvoir Publishing; Boston Center for the Arts; Corcept; CRICO; Dartmouth; Dey; LP/Mylan; Israel Society for Biological Psychiatry; Johns Hopkins University National Association of Continuing Education; PAI; Pamlab; Physicians Postgraduate Press; Ridge Diagnostics; Slack Publishing; Sunovion, Teva; University of Florida; University of Michigan; University of New Mexico; University of Miami; University of Wisconsin; Wolters Kluwer Publishing; Biogen Idec; Shire; Sunovion; National Alliance for Research on Schizophrenia and Depression; Tourette Syndrome Association; Obsessive-Compulsive Foundation; Tufts University; MGH Psychiatry Academy; BrainCells Inc; Systems Research and Applications Corporation; Boston University; Catalan Agency for Health Technology Assessment and Research; National Association of Social Workers Massachusetts; Massachusetts Medical Society; National Institute on Drug Abuse; Oxford University Press; National Institute on Aging; Agency for Healthcare Research and Quality; Janssen; Forest; Medtronic; Cyberonics; Northstar FX Dr Sylvia has been a consultant for Bracket Global and Clintara, has received research support from National Institute of Mental Health (NIMH), is a former stockholder in Concordant Rater Systems, and has received other financial or material support from New Harbinger Publishers. Dr Miklowitz has received research support or honoraria from NIMH, Brain and Behavior Research Foundation, Danny Alberts Foundation, and Attias Family Foundation and has received other financial or material support from Guilford Press and John Wiley and Sons. Dr Otto has been a consultant for MicroTransponder. Dr Frank has been a consultant for Servier and has received other financial or material support from Guilford Press and the American Psychological Association Press. Dr Berk is an employee of Barwon Health, Deakin University; has received research support from National Institutes of Health, National Health and Medical Research Council, and CRC Simons; has received honoraria from Lundbeck, AstraZeneca, Servier, Eli Lilly, and ISBD Korea; has been on the speakers/advisory boards of AstraZeneca, Lundbeck, Eli Lilly, and Janssen; and has received other financial or material support from Allen & Unwin and Cambridge University Press. Dr Nierenberg has received honoraria or travel expenses from American Society of Clinical Psychopharmacology, Australasian Society for Bipolar Disorder, Bayamon Region Psychiatric Society (San Juan, Puerto Rico), Belvoir Publishing, Boston Center for the Arts, Corcept, CRICO, Dartmouth, Dey, LP/Mylan, Israel Society for Biological Psychiatry, Johns Hopkins University National Association of Continuing Education, PAI, Pamlab, Physicians Postgraduate Press, Ridge Diagnostics, Slack Publishing, Sunovion, Teva, University of Florida, University of Michigan, University of New Mexico, University of Miami, University of Wisconsin, and Wolters Kluwer Publishing; has received potential consulting honoraria from AstraZeneca, Bristol-Myers Squibb, Forest, Pfizer, and Ridge Diagnostics; and has received potential support of research at MGH through Biogen Idec, Dey, Pamlab, Shire, and Sunovion. He owns stock options in Appliance Computing, Inc (MindSite.com) and Brain Cells, Inc. Additional income is possible from Infomedic.com depending on overall revenues of the company, but no revenue has been received to date. Through MGH, Dr Nierenberg is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Rating Scale exclusively licensed to the MGH Clinical Trials Network and Institute. Dr Deckersbach has received funding for his research from National Alliance for Research on Schizophrenia and Depression, Tourette Syndrome Association, Obsessive-Compulsive Foundation, and Tufts University; has received honoraria, consultation fees, and/or royalties from the MGH Psychiatry Academy, BrainCells Inc, Systems Research and Applications Corporation, Boston University, Catalan Agency for Health Technology Assessment and Research, National Association of Social Workers Massachusetts, Massachusetts Medical Society, Tufts University, National Institute on Drug Abuse, and Oxford University Press; and has participated in research funded by National Institutes of Health, National Institute on Aging, Agency for Healthcare Research and Quality, Janssen, Forest, Shire, Medtronic, Cyberonics, and Northstar. Mr Stange and Dr Magalhaes report no relevant financial interests. NR 77 TC 9 Z9 10 U1 5 U2 17 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2013 VL 74 IS 3 BP 249 EP 255 DI 10.4088/JCP.12m08019 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 117AY UT WOS:000316925700004 PM 23561230 ER PT J AU Wecht, JM Bauman, WA AF Wecht, Jill M. Bauman, William A. TI Decentralized cardiovascular autonomic control and cognitive deficits in persons with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Review DE Spinal cord injuries; Cerebral blood flow; Brain injury; Traumatic; Cognitive dysfunction; Arterial pressure; Heart rate; Arterial stiffness; Autonomic dysreflexia; Tetraplegia; Paraplegia; Neuropsychological testing; Rehabilitation ID PULSE-WAVE VELOCITY; LOW BLOOD-PRESSURE; SLEEP-APNEA SYNDROME; CONTINGENT NEGATIVE-VARIATION; INCREASED ARTERIAL STIFFNESS; HEART-RATE-VARIABILITY; ORTHOSTATIC HYPOTENSION; RISK-FACTORS; INTERNATIONAL STANDARDS; SUSTAINED ATTENTION AB Spinal cord injury (SCI) results in motor and sensory impairments that can be identified with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Although, SCI may disrupt autonomic neural transmission, less is understood regarding the clinical impact of decentralized autonomic control. Cardiovascular regulation may be altered following SCI and the degree of impairment may or may not relate to the level of AIS injury classification. In general, persons with lesions above T1 present with bradycardia, hypotension, and orthostatic hypotension; functional changes which may interfere with rehabilitation efforts. Although many individuals with SCI above T1 remain overtly asymptomatic to hypotension, we have documented deficits in memory and attention processing speed in hypotensive individuals with SCI compared to a normotensive SCI cohort. Reduced resting cerebral blood flow (CBF) and diminished CBF responses to cognitive testing relate to test performance in hypotensive non-SCI, and preliminary evidence suggests a similar association in individuals with SCI. Persons with paraplegia below T7 generally present with a normal cardiovascular profile; however, our group and others have documented persistently elevated heart rate and increased arterial stiffness. In the non-SCI literature there is evidence supporting a link between increased arterial stiffness and cognitive deficits. Preliminary evidence suggests increased incidence of cognitive impairment in individuals with paraplegia, which we believe may relate to adverse cardiovascular changes. This report reviews relevant literature and discusses findings related to the possible association between decentralized cardiovascular autonomic control and cognitive dysfunction in persons with SCI. C1 [Wecht, Jill M.; Bauman, William A.] James J Peters VA Med Ctr, Bronx, NY USA. [Wecht, Jill M.; Bauman, William A.] Mt Sinai Sch Med, Ctr Excellence & Med Serv, New York, NY USA. [Wecht, Jill M.; Bauman, William A.] Dept Med, New York, NY USA. [Wecht, Jill M.; Bauman, William A.] Dept Rehabil Med, New York, NY USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Room 1E-02,130 West Kingsbridge Rd, Bronx, NY USA. EM jm.wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [A6161W, B3203R, B4162C] FX This research was supported by the Veterans Affairs Rehabilitation Research and Development Service (Grants: A6161W, B3203R, and B4162C). NR 97 TC 5 Z9 6 U1 1 U2 16 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD MAR PY 2013 VL 36 IS 2 BP 74 EP 81 DI 10.1179/2045772312Y.0000000056 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 112RT UT WOS:000316611400002 PM 23809520 ER PT J AU Carbone, LD Chin, AS Lee, TA Burns, SP Svircev, JN Hoenig, HM Akhigbe, T Weaver, FM AF Carbone, Laura D. Chin, Amy S. Lee, Todd A. Burns, Stephen P. Svircev, Jelena N. Hoenig, Helen M. Akhigbe, Titilola Weaver, Frances M. TI The association of opioid use with incident lower extremity fractures in spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Fractures; Opioids; Bone mineral density; Osteoporosis; Spinal cord injuries; Rehabilitation; Veterans ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; CHRONIC PAIN; OLDER-ADULTS; PHARMACOLOGICAL-TREATMENTS; CALCIUM SUPPLEMENTATION; LONG-TERM; RISK; MEN; OSTEOPOROSIS AB Objective: To determine the association between opioid use and lower extremity fracture risk in men with spinal cord injury (SCI). Design: Retrospective cohort study. Setting: Veterans Affairs Healthcare System. Participants: In total, 7447 male Veterans with a history of a traumatic SCI identified from the Veterans Affairs (VA) Spinal Cord Dysfunction Registry (SCD) from September 2002 through October 2007 and followed through October 2010. Outcome measures: Incident lower extremity fractures by use of opioids. Results: In individuals identified from the VA SCD Registry 2002-2007, opioid use was quite common, with approximately 70% of the cohort having received a prescription for an opioid. Overall, there were 892 incident lower extremity fractures over the time period of this study (597 fractures in the opioid users and 295 fractures in the non-opioid users). After adjusting for covariates, there was a statistically significant relationship between opioid use and increased risk for lower extremity fractures (hazard ratio 1.82 (95% confidence interval 1.59-2.09)). Shorter duration of use (<6 months) and higher doses were positively related to fracture risk (P < 0.0001). Conclusions: Opioid use is quite common in SCI and is associated with an increased risk for lower extremity fractures. Careful attention to fracture prevention is warranted in patients with SCI, particularly upon initiation of an opioid prescription and when higher doses are used. C1 [Carbone, Laura D.; Akhigbe, Titilola] Vet Affairs Med Ctr, Dept Res, Memphis, TN USA. [Carbone, Laura D.; Akhigbe, Titilola] Univ Tennessee, Ctr Hlth Sci, Div Connect Tissues Disorders, Dept Med, Memphis, TN 38163 USA. [Chin, Amy S.; Weaver, Frances M.] Edward Hines Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL USA. [Lee, Todd A.] Univ Illinois, Chicago, IL USA. [Burns, Stephen P.; Svircev, Jelena N.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Burns, Stephen P.; Svircev, Jelena N.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hoenig, Helen M.] Durham Vet Affairs Med Ctr, Durham, NC USA. RP Carbone, LD (reprint author), Univ Tennessee, Ctr Hlth Sci, 956 Court Ave,Rm G326, Memphis, TN 38163 USA. EM lcarbone@uthsc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [IIR 08-033] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development #IIR 08-033. The authors thank Catherine Plunkett for her technical assistance in preparation of this manuscript. NR 53 TC 7 Z9 8 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD MAR PY 2013 VL 36 IS 2 BP 91 EP 96 DI 10.1179/2045772312Y.0000000060 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 112RT UT WOS:000316611400004 PM 23809522 ER PT J AU Harel, NY Asselin, PK Fineberg, DB Pisano, TJ Bauman, WA Spungen, AM AF Harel, Noam Y. Asselin, Pierre K. Fineberg, Drew B. Pisano, Thomas J. Bauman, William A. Spungen, Ann M. TI Adaptation of computerized posturography to assess seated balance in persons with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injuries; Paraplegia; Rehabilitation; Disability; Assistive technology; Berg balance scale; Limits of stability; Modified functional reach test; Posturography ID POSTURAL CONTROL; SCALE; RELIABILITY; VALIDITY; PERFORMANCE; STROKE AB Background: The ability to retain or improve seated balance function after spinal cord injury (SCI) may mean the difference between independence and requiring assistance for basic activities of daily living. Compared with assessments of standing and walking balance, seated balance assessments remain relatively underemphasized and under-utilized. Objective: To optimize tools for assessing seated balance deficits and recovery in SCI. Design: Cross-sectional observational study of different methods for assessing seated balance function. Setting: Veterans Affairs Center of Excellence for the Medical Consequences of Spinal Cord Injury. Participants: Seven able-bodied volunteers, seven participants with chronic motor-complete thoracic SCI. Interventions: A computerized pressure-plate apparatus designed for testing standing balance was adapted into a seated balance assessment system. Outcome measures: Seated section of Berg Balance Scale; modified functional reach test; and two posturography tests: limits of stability and clinical test of sensory integration on balance. Results: Seated posturography demonstrated improved correlation with neurological level of lesion compared to that of routinely applied subjective clinical tests. Conclusion: Seated posturography represents an appealing outcome measure that may be applied toward the measurement of functional changes in response to various rehabilitation interventions in individuals with paralysis. C1 [Harel, Noam Y.; Asselin, Pierre K.; Fineberg, Drew B.; Pisano, Thomas J.; Bauman, William A.; Spungen, Ann M.] James J Peters Vet Affairs Med Ctr, VA RR&D Ctr Excellence Med Consequences Spinal Co, Bronx, NY 10468 USA. [Harel, Noam Y.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Harel, Noam Y.; Bauman, William A.; Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Pisano, Thomas J.] Robert Wood Johnson Med Sch, Piscataway, NJ USA. [Bauman, William A.; Spungen, Ann M.] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. RP Harel, NY (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM noam.harel@va.gov FU VA Rehabilitation Research & Development (RRD) Service; RR&D National Center of Excellence for the Medical Consequences of Spinal Cord Injury [B9212-C]; James J. Peters Veterans Affairs Medical Center (JJPVAMC); Mount Sinai School of Medicine Department of Neurology FX The authors wish to thank the VA Rehabilitation Research & Development (RR&D) Service, the RR&D National Center of Excellence for the Medical Consequences of Spinal Cord Injury (#B9212-C), the James J. Peters Veterans Affairs Medical Center (JJPVAMC), and the Mount Sinai School of Medicine Department of Neurology for providing research and salary support. We would also like to specifically thank Steven Knezevic for his assistance, and the Audiology Service, JJPVAMC, for generously providing us access to the Smart EquiTest apparatus. NR 19 TC 3 Z9 3 U1 4 U2 15 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD MAR PY 2013 VL 36 IS 2 BP 127 EP 133 DI 10.1179/2045772312Y.0000000053 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 112RT UT WOS:000316611400009 PM 23809527 ER PT J AU Thrall, JH AF Thrall, James H. TI Data Mining, Knowledge Creation, and Work Process Enhancement in the Second Generation of Radiology's Digital Age SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,Room 216, Boston, MA 02114 USA. EM jthrall@partners.org NR 0 TC 5 Z9 5 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2013 VL 10 IS 3 BP 161 EP 162 DI 10.1016/j.jacr.2012.08.007 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 113ET UT WOS:000316650000003 PM 23571055 ER PT J AU del Campo, JM Sessa, C Krasner, CN Vermorken, JB Colombo, N Kaye, S Gore, M Zintl, P Gomez, J Parekh, T Park, YC McMeekin, S AF Maria del Campo, Jose Sessa, Cristiana Krasner, Carolyn N. Vermorken, Jan B. Colombo, Nicoletta Kaye, Stan Gore, Martin Zintl, Patrik Gomez, Javier Parekh, Trilok Park, Youn Choi McMeekin, Scott TI Trabectedin as single agent in relapsed advanced ovarian cancer: results from a retrospective pooled analysis of three phase II trials SO MEDICAL ONCOLOGY LA English DT Article DE Trabectedin; Recurrent ovarian cancer; Pooled analysis ID GYNECOLOGIC-ONCOLOGY-GROUP; PEGYLATED LIPOSOMAL DOXORUBICIN; PLATINUM-CONTAINING CHEMOTHERAPY; PROLONGED ORAL ETOPOSIDE; DNA-REPAIR PATHWAYS; PHASE-II; HOMOLOGOUS RECOMBINATION; NUCLEOTIDE-EXCISION; SENSITIVE OVARIAN; UNIQUE MECHANISM AB Three phase II studies evaluated trabectedin monotherapy as second-/third-line therapy in patients with refractory/recurrent ovarian cancer (ROC). Three different schedules were investigated: 3-h infusion every 3 weeks (3-h_q3w), 24-h infusion q3w (24-h_q3w), and 3-h weekly infusion for 3 weeks of a 4-week cycle. This retrospective pooled analysis evaluated the efficacy and the safety profile of trabectedin according to each administered regimen. Data from 295 patients were used to compare weekly versus q3w schedules, and 3-h versus 24-h infusion given q3w. Both q3w regimens showed higher overall response rate (36 vs. 16 %; p = 0.0001), disease control rate (66 vs. 46 %; p = 0.0007), and longer median progression-free survival (5.6 vs. 2.8 months; p < 0.0001) than the weekly schedule. Comparable activity was observed for the 3- and 24-h infusions q3w. Common adverse events were nausea, fatigue, vomiting, transient neutropenia, and transaminase increases. A better safety profile regarding neutropenia, fatigue, and vomiting was seen for the 3-h_ q3w regimen as compared to the 24-h_q3w one. Trabectedin given as a single agent q3w as 3-h infusion is the schedule of choice for the treatment of ROC, and its efficacy and safety profile favorably compares with other active salvage treatments. C1 [Maria del Campo, Jose] Vall dHebron Univ Hosp, Dept Med Oncol, Gynecol Head & Neck Canc Div, Barcelona 08035, Spain. [Sessa, Cristiana] Ist Oncol Svizzera Italiana, Div Med Oncol, CH-6500 Bellinzona, Switzerland. [Sessa, Cristiana] Fdn IRCCS Ist Nazl Tumori, I-20133 Milan, Italy. [Krasner, Carolyn N.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Vermorken, Jan B.] Univ Antwerp Hosp, Dept Med Oncol, B-2650 Edegem, Belgium. [Colombo, Nicoletta] Univ Milano Bicocca, Dept Med Oncol, I-20141 Milan, Italy. [Kaye, Stan] Royal Marsden Hosp, Inst Canc Res, Dept Med Oncol, Sutton SM2 5PT, Surrey, England. [Gore, Martin] Royal Marsden Hosp, Dept Med, London SW3 6JJ, England. [Zintl, Patrik; Gomez, Javier] PharmaMar, Madrid, Spain. [Parekh, Trilok; Park, Youn Choi] Janssen Res & Dev LLC, Raritan, NJ 08869 USA. [McMeekin, Scott] Univ Oklahoma, Gynecol Oncol Sect, Oklahoma City, OK 73190 USA. RP del Campo, JM (reprint author), Vall dHebron Univ Hosp, Dept Med Oncol, Gynecol Head & Neck Canc Div, Passeig Vall dHebron 119-129, Barcelona 08035, Spain. EM jmcampo@vhebron.net; cristiana.sessa@eoc.ch; cnkrasner@partners.org; Jan.B.Vermorken@uza.be; nicoletta.colombo@ieo.it; stan.kaye@rmh.nhs.uk; Martin.Gore@rmh.nthames.nhs.uk; pzintl@pharmamar.com; jgomez@pharmamar.com; TParekh1@ITS.JNJ.COM; YPark3@its.jnj.com; scott-mcmeekin@ouhsc.edus FU PharmaMar, Madrid, Spain; Janssen Research & Development, L.L.C., Raritan, NJ, USA FX The authors would like to acknowledge Antonio Nieto, James Jiao for data analysis and Adnan Tanovic for writing assistance for the manuscript. Those studies were supported by funding form PharmaMar, Madrid, Spain, and Janssen Research & Development, L.L.C., Raritan, NJ 08869, USA. NR 48 TC 12 Z9 12 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD MAR PY 2013 VL 30 IS 1 AR 435 DI 10.1007/s12032-012-0435-1 PG 11 WC Oncology SC Oncology GA 115GO UT WOS:000316800800113 PM 23397080 ER PT J AU Papakostas, GI Shelton, RC Kinrys, G Henry, ME Bakow, BR Lipkin, SH Pi, B Thurmond, L Bilello, JA AF Papakostas, G. I. Shelton, R. C. Kinrys, G. Henry, M. E. Bakow, B. R. Lipkin, S. H. Pi, B. Thurmond, L. Bilello, J. A. TI Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a Pilot and Replication Study SO MOLECULAR PSYCHIATRY LA English DT Article DE major depressive disorder; biomarkers; diagnosis; test ID VS. UNSTRUCTURED INTERVIEWS; SEROTONIN TRANSPORTER GENE; CATECHOLAMINE HYPOTHESIS; ENDOGENOUS-DEPRESSION; MISSING HERITABILITY; PSYCHIATRIC-PATIENTS; NEUROTROPHIC FACTOR; SUPPORTING EVIDENCE; TREATMENT RESPONSE; MOOD DISORDERS AB Despite decades of intensive research, the development of a diagnostic test for major depressive disorder (MDD) had proven to be a formidable and elusive task, with all individual marker-based approaches yielding insufficient sensitivity and specificity for clinical use. In the present work, we examined the diagnostic performance of a multi-assay, serum-based test in two independent samples of patients with MDD. Serum levels of nine biomarkers (alpha1 antitrypsin, apolipoprotein CIII, brain-derived neurotrophic factor, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resistin and soluble tumor necrosis factor alpha receptor type II) in peripheral blood were measured in two samples of MDD patients, and one of the non-depressed control subjects. Biomarkers measured were agreed upon a priori, and were selected on the basis of previous exploratory analyses in separate patient/control samples. Individual assay values were combined mathematically to yield an MDDScore. A 'positive' test, (consistent with the presence of MDD) was defined as an MDDScore of 50 or greater. For the Pilot Study, 36 MDD patients were recruited along with 43 non-depressed subjects. In this sample, the test demonstrated a sensitivity and specificity of 91.7% and 81.3%, respectively, in differentiating between the two groups. The Replication Study involved 34 MDD subjects, and yielded nearly identical sensitivity and specificity (91.1% and 81%, respectively). The results of the present study suggest that this test can differentiate MDD subjects from non-depressed controls with adequate sensitivity and specificity. Further research is needed to confirm the performance of the test across various age and ethnic groups, and in different clinical settings. Molecular Psychiatry (2013) 18, 332-339; doi:10.1038/mp.2011.166; published online 13 December 2011 C1 [Papakostas, G. I.; Bakow, B. R.; Lipkin, S. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papakostas, G. I.; Bakow, B. R.; Lipkin, S. H.] Harvard Univ, Sch Med, Boston, MA USA. [Shelton, R. C.] Vanderbilt Univ, Nashville, TN USA. [Kinrys, G.] Cambridge Hlth Alliance, Cambridge, MA USA. [Kinrys, G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Henry, M. E.] St Elizabeths Med Ctr, Brighton, MA USA. [Pi, B.; Thurmond, L.; Bilello, J. A.] Ridge Diagnost, Res Triangle Pk, NC USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Ridge Diagnostics; Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Pfizer; Eli Lilly and Company; GlaxoSmithKline Pharmaceuticals; Janssen Pharmaceutica; Sanofi Pharmaceutica; Wyeth-Ayerst Laboratories; AstraZeneca Pharmaceutica; Abbott Laboratories; AstraZeneca; Bristol Myers Squibb; Cephalon; Elan Pharmaceuticals; Eli Lilly; Forest Laboratories; Glaxo SmithKline; Janssen; Sanofi-Aventis; Sepracor; UCB Pharma; Wyeth-Ayerst; Shire; Forest; Sunovion; Bracco Diagnostics; GlaxoSmithKline; NARSAD; National Science Foundation FX George Papakostas: Dr Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca PLC, Brainsway, Bristol-Myers Squibb Company, Cephalon, Eli Lilly, GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals and Wyeth. He has received honoraria from Abbott Laboratories, Astra Zeneca PLC, Bristol-Myers Squibb Company, Brainsway, Cephalon, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Titan Pharmaceuticals and Wyeth. He has received research support from Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer and Ridge Diagnostics (formerly known as Precision Human Biolaboratories). Finally, Dr Papakostas has served (in the past, but not currently) on the speaker's bureaus for Bristol-MyersSquibb Co and Pfizer.; Richard Shelton: Dr Shelton has received Grant/research support from Eli Lilly and Company; GlaxoSmithKline Pharmaceuticals; Janssen Pharmaceutica; Pfizer; Sanofi Pharmaceutica; Wyeth-Ayerst Laboratories; AstraZeneca Pharmaceutica; Ridge Diagnostics; and Abbott Laboratories. He has been a paid consultant to Pfizer; Ridge Diagnostics and Janssen Pharmaceutica. He has served on speaker's bureaus for Bristol-Myers Squibb Company; Eli Lilly and Company; Janssen Pharmaceutica; Pfizer; GlaxoSmithKline Pharmaceuticals; Solvay Pharmaceuticals; Wyeth-Ayerst Laboratories and Abbott Laboratories.; Gustavo Kinrys: Dr Kinrys has served as an Advisor and/or consultant to AstraZeneca, Cephalon, Forest Laboratories, Glaxo SmithKline, Pfizer, Sepracor, UCB Pharma and Wyeth-Ayerst. Dr Kinrys has received research support from AstraZeneca, Bristol Myers Squibb, Cephalon, Elan Pharmaceuticals, Eli Lilly, Forest Laboratories, Glaxo SmithKline, Janssen, Pfizer, Ridge Diagnostics, Sanofi-Aventis, Sepracor, UCB Pharma and Wyeth-Ayerst. Dr Kinrys has served on the speaker's bureaus of Glaxo SmithKline, Janssen, and Wyeth-Ayerst.; Michael Henry: Dr Henry has received consulting fees from Ridge Diagnostics and research support from Shire, Forest, Sunovion, Eli Lilly, Bracco Diagnostics, Pfizer, GlaxoSmithKline, NARSAD and Ridge Diagnostics.; Bo Pi: Dr Pi is an employee of and holds stock in Ridge Diagnostics. Dr Pi has received research funding from the National Science Foundation as well as the National Institute of Mental Health. Dr Pi holds several patents and has several patents pending involving the use of biomarkers in major depressive disorder. NR 54 TC 59 Z9 60 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2013 VL 18 IS 3 BP 332 EP 339 DI 10.1038/mp.2011.166 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 112BZ UT WOS:000316568100010 PM 22158016 ER PT J AU Gamazon, ER Badner, JA Cheng, L Zhang, C Zhang, D Cox, NJ Gershon, ES Kelsoe, JR Greenwood, TA Nievergelt, CM Chen, C McKinney, R Shilling, PD Schork, NJ Smith, EN Bloss, CS Nurnberger, JI Edenberg, HJ Foroud, T Koller, DL Scheftner, WA Coryell, W Rice, J Lawson, WB Nwulia, EA Hipolito, M Byerley, W McMahon, FJ Schulze, TG Berrettini, WH Potash, JB Zandi, PP Mahon, PB McInnis, MG Zollner, S Zhang, P Craig, DW Szelinger, S Barrett, TB Liu, C AF Gamazon, E. R. Badner, J. A. Cheng, L. Zhang, C. Zhang, D. Cox, N. J. Gershon, E. S. Kelsoe, J. R. Greenwood, T. A. Nievergelt, C. M. Chen, C. McKinney, R. Shilling, P. D. Schork, N. J. Smith, E. N. Bloss, C. S. Nurnberger, J. I. Edenberg, H. J. Foroud, T. Koller, D. L. Scheftner, W. A. Coryell, W. Rice, J. Lawson, W. B. Nwulia, E. A. Hipolito, M. Byerley, W. McMahon, F. J. Schulze, T. G. Berrettini, W. H. Potash, J. B. Zandi, P. P. Mahon, P. B. McInnis, M. G. Zoellner, S. Zhang, P. Craig, D. W. Szelinger, S. Barrett, T. B. Liu, C. TI Enrichment of cis-regulatory gene expression SNPs and methylation quantitative trait loci among bipolar disorder susceptibility variants SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar disorder; eQTL; GWAS; mQTL ID GENOME-WIDE ASSOCIATION; HUMAN-DISEASE; EPIGENETICS AB We conducted a systematic study of top susceptibility variants from a genome-wide association (GWA) study of bipolar disorder to gain insight into the functional consequences of genetic variation influencing disease risk. We report here the results of experiments to explore the effects of these susceptibility variants on DNA methylation and mRNA expression in human cerebellum samples. Among the top susceptibility variants, we identified an enrichment of cis regulatory loci on mRNA expression (eQTLs), and a significant excess of quantitative trait loci for DNA CpG methylation, hereafter referred to as methylation quantitative trait loci (mQTLs). Bipolar disorder susceptibility variants that cis regulate both cerebellar expression and methylation of the same gene are a very small proportion of bipolar disorder susceptibility variants. This finding suggests that mQTLs and eQTLs provide orthogonal ways of functionally annotating genetic variation within the context of studies of pathophysiology in brain. No lymphocyte mQTL enrichment was found, suggesting that mQTL enrichment was specific to the cerebellum, in contrast to eQTLs. Separately, we found that using mQTL information to restrict the number of single-nucleotide polymorphisms studied enhances our ability to detect a significant association. With this restriction a priori informed by the observed functional enrichment, we identified a significant association (rs12618769, P-bonferroni < 0.05) from two other GWA studies (TGen + GAIN; 2191 cases and 1434 controls) of bipolar disorder, which we replicated in an independent GWA study (WTCCC). Collectively, our findings highlight the importance of integrating functional annotation of genetic variants for gene expression and DNA methylation to advance the biological understanding of bipolar disorder. Molecular Psychiatry (2013) 18, 340-346; doi:10.1038/mp.2011.174; published online 3 January 2012 C1 [Gamazon, E. R.; Cox, N. J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Badner, J. A.; Gershon, E. S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Cheng, L.; Zhang, C.; Chen, C.; Liu, C.] Univ Illinois, Dept Psychiat, Chicago, IL 60607 USA. [Zhang, D.] Zhejiang Univ, Sch Med, Hangzhou, Zhejiang, Peoples R China. [Kelsoe, J. R.; Greenwood, T. A.; Nievergelt, C. M.; McKinney, R.; Shilling, P. D.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Schork, N. J.; Smith, E. N.; Bloss, C. S.] Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA USA. [Nurnberger, J. I.; Koller, D. L.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. [Edenberg, H. J.; Foroud, T.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Scheftner, W. A.] Rush Univ, Dept Psychiat, Chicago, IL 60612 USA. [Coryell, W.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Rice, J.] Washington Univ, Div Biostat, St Louis, MO USA. [Lawson, W. B.; Nwulia, E. A.; Hipolito, M.] Howard Univ, Dept Psychiat, Washington, DC 20059 USA. [Byerley, W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [McMahon, F. J.; Schulze, T. G.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Intramural Res Program, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Schulze, T. G.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany. [Berrettini, W. H.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Potash, J. B.; Zandi, P. P.; Mahon, P. B.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. [McInnis, M. G.; Zoellner, S.; Zhang, P.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Craig, D. W.; Szelinger, S.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. [Barrett, T. B.] Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. RP Liu, C (reprint author), Univ Illinois, Dept Psychiat, 900 S Ashland Ave,Room 1006, Chicago, IL 60607 USA. EM cliu@psych.uic.edu RI Schulze, Thomas/H-2157-2013; Zhang, Peng/N-2920-2014; OI Zhang, Peng/0000-0003-1182-1392; Nievergelt, Caroline/0000-0001-5766-8923; Lawson, William/0000-0002-9324-7090; McMahon, Francis/0000-0002-9469-305X; Greenwood, Tiffany/0000-0002-6080-6503; Nurnberger, John/0000-0002-7674-1767; Edenberg, Howard/0000-0003-0344-9690; Gamazon, Eric/0000-0003-4204-8734 FU PAAR (Pharmacogenetics of Anti-cancer Agents Research) [U01 GM61393]; ENDGAMe (ENhancing Development of Genome-wide Association Methods) initiative [U01 HL084715]; Genotype-Tissue Expression project (GTeX) [R01 MH090937]; [5R01MH080425] FX This work was funded by 5R01MH080425 (to CL), PAAR (Pharmacogenetics of Anti-cancer Agents Research; U01 GM61393), ENDGAMe (ENhancing Development of Genome-wide Association Methods) initiative (U01 HL084715), and the Genotype-Tissue Expression project (GTeX) (R01 MH090937) (to NJC). NR 28 TC 57 Z9 57 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2013 VL 18 IS 3 BP 340 EP 346 DI 10.1038/mp.2011.174 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 112BZ UT WOS:000316568100011 PM 22212596 ER PT J AU Goetz, CG Stebbins, GT Chung, KA Hauser, RA Miyasaki, JM Nicholas, AP Poewe, W Seppi, K Rascol, O Stacy, MA Nutt, JG Tanner, CM Urkowitz, A Jaglin, JA Ge, S AF Goetz, Christopher G. Stebbins, Glenn T. Chung, Kathryn A. Hauser, Robert A. Miyasaki, Janis M. Nicholas, Anthony P. Poewe, Werner Seppi, Klaus Rascol, Olivier Stacy, Mark A. Nutt, John G. Tanner, Caroline M. Urkowitz, Alison Jaglin, Jean A. Ge, Song TI Which dyskinesia scale best detects treatment response? SO MOVEMENT DISORDERS LA English DT Article DE dyskinesia; Parkinson's disease; rating scales; clinimetrics; amantadine; clinical trials ID PARKINSONS-DISEASE; RATING-SCALE; PD; THERAPIES; TRIALS; UPDATE; DRUGS AB Numerous scales assess dyskinesia in Parkinson's disease (PD), variably focusing on anatomical distribution, phenomenology, time, severity, and disability. No study has compared these scales and their relative ability to detect change related to an established treatment. We conducted a randomized placebo-controlled trial of amantadine, assessing dyskinesia at baseline and at 4 and 8 weeks using the following scales: Unified Dyskinesia Rating Scale (UDysRS), Lang-Fahn Activities of Daily Living Dyskinesia Rating Scale (LF), 26-Item Parkinson's Disease Dyskinesia scale (PDD-26), patient diaries, modified Abnormal Involuntary Movements Scale (AIMS), Rush Dyskinesia Rating Scale (RDRS), dyskinesia items from the Movement Disorder Societysponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and Clinical Global Impression (severity and change: CGI-S, CGI-C). Scale order was randomized at each visit, but raters were aware of each scale as it was administered. Sensitivity to treatment was assessed using effect size. Sixty-one randomized dyskinetic PD subjects (31 amantadine, 30 placebo) completed the study. Four of the 8 scales (CGI-C, LF, PDD-26, and UDysRS) detected a significant treatment. The UDysRS Total Score showed the highest effect size (2 = 0.138) for detecting treatment-related change, with all other scales having effect sizes < 0.1. No scale was resistant to placebo effects. This study resolves 2 major issues useful for future testing of new antidyskinesia treatments: among tested scales, the UDysRS, having both subjective and objective dyskinesia ratings, is superior for detecting treatment effects; and the magnitude of the UDysRS effect size from amantadine sets a clear standard for comparison for new agents. (c) 2012 Movement Disorder Society C1 [Goetz, Christopher G.; Stebbins, Glenn T.; Jaglin, Jean A.; Ge, Song] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Chung, Kathryn A.; Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. [Chung, Kathryn A.; Nutt, John G.] Portland VA Med Ctr, Portland, OR USA. [Hauser, Robert A.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. [Miyasaki, Janis M.] Univ Toronto, Edmond J Safra Program Parkinsons Dis, Toronto, ON, Canada. [Nicholas, Anthony P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Nicholas, Anthony P.] Birmingham VA Med Ctr, Birmingham, AL USA. [Poewe, Werner; Seppi, Klaus] Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria. [Rascol, Olivier] Univ Hosp Toulouse, Clin Invest Ctr CIC9302, Toulouse, France. [Rascol, Olivier] Univ Hosp Toulouse, INSERM, Dept Clin Pharmacol, Toulouse, France. [Rascol, Olivier] Univ Hosp Toulouse, INSERM, Dept Neurosci, Toulouse, France. [Rascol, Olivier] Univ Toulouse 3, F-31062 Toulouse, France. [Stacy, Mark A.] Duke Univ, Dept Neurol, Durham, NC USA. [Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA USA. [Tanner, Caroline M.] Ctr Clin, Sunnyvale, CA USA. [Urkowitz, Alison] Michael J Fox Fdn Parkinsons Res, New York, NY USA. RP Goetz, CG (reprint author), Rush Presbyterian St Lukes Med Ctr, Suite 755,1725 W Harrison St, Chicago, IL 60612 USA. EM cgoetz@rush.edu OI Miyasaki, Janis/0000-0002-6372-6007 FU Michael J. Fox Foundation for Parkinson's Research; Parkinson's Disease Foundation FX The trial was sponsored by a grant from the Michael J. Fox Foundation for Parkinson's Research. The Rush Movement Disorder Program is also supported by the Parkinson's Disease Foundation. NR 26 TC 19 Z9 19 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2013 VL 28 IS 3 BP 341 EP 346 DI 10.1002/mds.25321 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 113VF UT WOS:000316696700020 PM 23390076 ER PT J AU Wills, AMA Eberly, S Tennis, M Lang, AE Messing, S Togasaki, D Tanner, CM Kamp, C Chen, JF Oakes, D McDermott, MP Schwarzschild, MA AF Wills, Anne-Marie A. Eberly, Shirley Tennis, Marsha Lang, Anthony E. Messing, Susan Togasaki, Daniel Tanner, Caroline M. Kamp, Cornelia Chen, Jiang-Fan Oakes, David McDermott, Michael P. Schwarzschild, Michael A. CA Parkinson Study Grp TI Caffeine consumption and risk of dyskinesia in CALM-PD SO MOVEMENT DISORDERS LA English DT Article DE caffeine; adenosine; Parkinson's disease; PD; dyskinesia ID RANDOMIZED CONTROLLED-TRIAL; ADENOSINE A(2A) RECEPTORS; PARKINSONS-DISEASE; ISTRADEFYLLINE KW-6002; LEVODOPA AB Background Adenosine A2A receptor antagonists reduce or prevent the development of dyskinesia in animal models of levodopa-induced dyskinesia. Methods We examined the association between self-reported intake of the A2A receptor antagonist caffeine and time to dyskinesia in the Comparison of the Agonist Pramipexole with Levodopa on Motor Complications of Parkinson's Disease (CALM-PD) and CALM Cohort extension studies, using a Cox proportional hazards model adjusting for age, baseline Parkinson's severity, site, and initial treatment with pramipexole or levodopa. Results For subjects who consumed >12 ounces of coffee/day, the adjusted hazard ratio for the development of dyskinesia was 0.61 (95% CI, 0.371.01) compared with subjects who consumed <4 ounces/day. For subjects who consumed between 4 and 12 ounces/day, the adjusted hazard ratio was 0.73 (95% CI, 0.461.15; test for trend, P = .05). Conclusions These results support the possibility that caffeine may reduce the likelihood of developing dyskinesia. (c) 2013 Movement Disorder Society C1 [Wills, Anne-Marie A.; Tennis, Marsha; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eberly, Shirley; Messing, Susan; Oakes, David; McDermott, Michael P.] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA. [Lang, Anthony E.] Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. [Lang, Anthony E.] Univ Hlth Network, Edmond J Safra Program Parkinsons Dis, Toronto, ON, Canada. [Togasaki, Daniel] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA USA. [Kamp, Cornelia; McDermott, Michael P.] Univ Rochester, Dept Neurol, Ctr Human Expt Therapeut, Rochester, NY USA. [Chen, Jiang-Fan] Boston Univ, Mol Neuropharmacol Lab, Boston, MA 02215 USA. RP Schwarzschild, MA (reprint author), MassGen Inst Neurodegenerat Dis, 114 16th St, Boston, MA 02129 USA. EM michaels@helix.mgh.harvard.edu FU Michael J. Fox Foundation for Parkinson's Research Fast Track Program; Parkinson's Disease Foundation; NIH [R01NS054978, K24NS60991] FX The study was supported by the Michael J. Fox Foundation for Parkinson's Research Fast Track 2001 Program, the Parkinson's Disease Foundation, and NIH grants R01NS054978 and K24NS60991. NR 21 TC 15 Z9 15 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2013 VL 28 IS 3 BP 380 EP 383 DI 10.1002/mds.25319 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 113VF UT WOS:000316696700025 PM 23339054 ER PT J AU Gomperts, SN Johnson, KA Growdon, J AF Gomperts, Stephen N. Johnson, Keith A. Growdon, John TI Reply: Beyond the limits of detection: Failure of PiB imaging to capture true A burden SO MOVEMENT DISORDERS LA English DT Letter ID LEWY BODY DISEASES; PARKINSON-DISEASE; DEMENTIA; DEPOSITION; PATHOLOGY; DLB; PDD C1 [Gomperts, Stephen N.; Johnson, Keith A.; Growdon, John] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gomperts, SN (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM sgomperts@partners.org FU NIA NIH HHS [R01 AG027435, P01 AG036694, P50 AG005134, R01 AG037497, U01 AG016976] NR 9 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2013 VL 28 IS 3 BP 407 EP 407 DI 10.1002/mds.25309 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 113VF UT WOS:000316696700038 PM 23401107 ER PT J AU Gray, PJ Efstathiou, JA AF Gray, Phillip J. Efstathiou, Jason A. TI Proton therapy-revolutionary advance or diminishing returns? SO NATURE REVIEWS UROLOGY LA English DT Editorial Material ID MODULATED RADIATION-THERAPY; LOCALIZED PROSTATE-CANCER; RANDOMIZED-TRIAL; ADENOCARCINOMA; TOXICITY; COLLEGE AB Proton therapy is a promising but costly technology for the treatment of prostate cancer. Although compelling evidence has shown proton therapy to be safe and effective for cancer treatment, comparative randomized data are needed to clarify its role and value in future practice. Gray, P.J. & Efstathiou, J.A. Nat. Rev. Urol. 10, 128-129 (2013); published online 12 February 2013; doi:10.1038/nrurol.2013.16 C1 [Gray, Phillip J.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 10 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 J9 NAT REV UROL JI Nat. Rev. Urol. PD MAR PY 2013 VL 10 IS 3 BP 128 EP 129 DI 10.1038/nrurol.2013.16 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 114AQ UT WOS:000316712500001 PM 23399730 ER PT J AU Weiser, TG Porter, MP Maier, RV AF Weiser, Thomas G. Porter, Michael P. Maier, Ronald V. TI Safety in the operating theatre-a transition to systems-based care SO NATURE REVIEWS UROLOGY LA English DT Review ID SURGICAL-SITE INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; SUPPLEMENTAL PERIOPERATIVE OXYGEN; IN-HOSPITAL MORTALITY; ARTERY-BYPASS-SURGERY; INTERMITTENT PNEUMATIC COMPRESSION; ASSESSMENT PROGRAM SCOAP; BETA-BLOCKER WITHDRAWAL; CRITICALLY-ILL PATIENTS; WOUND-INFECTION AB All surgeons want the best, safest care for their patients, but providing this requires the complex coordination of multiple disciplines to ensure that all elements of care are timely, appropriate, and well organized. Quality-improvement initiatives are beginning to lead to improvements in the quality of care and coordination amongst teams in the operating room. As the population ages and patients present with more complex disease pathology, the demands for efficient systematization will increase. Although evidence suggests that postoperative mortality rates are declining, there is substantial room for improvement. Multiple quality metrics are used as surrogates for safe care, but surgical teams including surgeons, anaesthetists, and nurses must think beyond these simple interventions if they are to effectively communicate and coordinate in the face of increasing demands. Weiser, T. G. et al. Nat. Rev. Urol. 10, 161-173; published online 19 February 2013; doi:10.1038/nrurol.2013.13 C1 [Weiser, Thomas G.] Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA. [Porter, Michael P.] Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. RP Weiser, TG (reprint author), Stanford Univ, Med Ctr, Dept Surg, 300 Pasteur Dr S067, Stanford, CA 94305 USA. EM tweiser@stanford.edu NR 169 TC 0 Z9 0 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 EI 1759-4820 J9 NAT REV UROL JI Nat. Rev. Urol. PD MAR PY 2013 VL 10 IS 3 BP 161 EP 173 DI 10.1038/nrurol.2013.13 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 114AQ UT WOS:000316712500007 PM 23419492 ER PT J AU Goyal, RK Sullivan, MP Chaudhury, A AF Goyal, R. K. Sullivan, M. P. Chaudhury, A. TI Progress in understanding of inhibitory purinergic neuromuscular transmission in the gut SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE ATP; exocytosis from nerve terminals; myosin Va; P2Y1 receptor; P2Y1-/- mice; PDGFR alpha plus fibroblast-like cell; SLC17A9; beta-NAD ID PIG SMALL-INTESTINE; NITRIC-OXIDE; ANOCOCCYGEUS MUSCLE; SMOOTH-MUSCLE; ATP RECEPTOR; PEPTIDE-VIP; MYOSIN VA; COLON; NEUROTRANSMISSION; RELEASE AB Recent studies with genetic deletion of P2Y1 receptor (P2Y1-/-) have clinched its role in enteric purinergic inhibitory neurotransmission and suggested that beta-NAD may be the purinergic inhibitory neurotransmitter in the colon. In this issue of the Journal, Gil and colleagues extend their earlier observations to the cecum and gastric antrum, showing that P2Y1 receptor mediated purinergic inhibition may be a general phenomenon in the gut. However, the authors made an unexpected observation in contrast with their earlier findings in the colon that neither the selective P2Y1 receptor antagonist MRS2500, nor P2Y1 receptor deletion, blocked the hyperpolarizing action of beta-NAD in the cecum. These observations suggest that beta-NAD may be the purinergic inhibitory neurotransmitter in the colon, but not in the cecum. This group had previously reported that the selective P2Y1 receptor antagonist MRS 2179 suppressed the hyperpolarizing action of ATP or ADP. Further studies are now needed to determine whether the hyperpolarizing actions of ATP and ADP are suppressed by the more potent P2Y1 antagonist MRS2500, and in P2Y1-/- mutants to test the intriguing possibility that different purines serve as purinergic inhibitory neurotransmitters in the colon and cecum and perhaps in different parts of the gut. Studies in P2Y1-/- mice will resolve other issues in purinergic neurotransmission including cellular localization of the beta-NAD or ATP-activated P2Y1 receptors on either smooth muscle cells or PDGFR alpha+ fibroblast-like cells, relationship of purinergic to nitrergic neurotransmission and understanding the physiological and clinical importance of purinergic transmission in gastrointestinal motility and its disorders. C1 VA Boston HealthCare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goyal, RK (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res 151,1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM raj_goyal@hms.harvard.edu FU Public Health Service grant [DK062867, BX001790] FX This report was supported by a Public Health Service grant (DK062867 to RKG and BX001790 to MPS). NR 36 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAR PY 2013 VL 25 IS 3 BP 203 EP 207 DI 10.1111/nmo.12090 PG 5 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 113UG UT WOS:000316693800008 PM 23414428 ER PT J AU Chitnis, T Tardieu, M Amato, MP Banwell, B Bar-Or, A Ghezzi, A Kornberg, A Krupp, LB Pohl, D Rostasy, K Tenembaum, S Waubant, E Wassmer, E AF Chitnis, Tanuja Tardieu, Marc Amato, Maria Pia Banwell, Brenda Bar-Or, Amit Ghezzi, Angelo Kornberg, Andrew Krupp, Lauren B. Pohl, Daniela Rostasy, Kevin Tenembaum, Silvia Waubant, Emmanuelle Wassmer, Evangeline TI International Pediatric MS Study Group Clinical Trials Summit Meeting report SO NEUROLOGY LA English DT Review ID ONSET MULTIPLE-SCLEROSIS; DEMYELINATING SYNDROMES; PSYCHOSOCIAL FEATURES; CHILDHOOD-ONSET; JUVENILE MS; CHILDREN; DISEASE; LESIONS; COHORT; ADULTS AB Objective: Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research. Methods: The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion. A total of 69 meeting attendees were assembled, including 35 academic experts. Regulatory and pharmaceutical representatives also attended, and provided input, which informed academic expert consensus decisions. Results: The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic, safety and efficacy data, and regulatory approval allowing for greater medication access. The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials. An international standardized cognitive battery was identified. The pros and cons of various trial designs were discussed. Guidelines surrounding MRI studies, pharmacokinetics, pharmacodynamics, and registries were developed. The academic experts agreed that given the limited subject pool, a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion. Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge. Conclusion: Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts, informed by regulatory and industry stakeholders. Neurology (R) 2013; 80:1161-1168 C1 [Chitnis, Tanuja] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Tardieu, Marc] Hop Univ Paris Sud, Assistance Publ Hop Paris, Paris, France. [Amato, Maria Pia] Univ Florence, Dept Neurol, Florence, Italy. [Banwell, Brenda] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Bar-Or, Amit] McGill Univ, Montreal Neurol Inst & Hosp, Montreal, PQ, Canada. [Ghezzi, Angelo] Hosp Gallarate, Multiple Sclerosis Study Ctr, Gallarate, Italy. [Kornberg, Andrew] Royal Childrens Hosp, Parkville, Vic 3052, Australia. [Krupp, Lauren B.] Lourie Ctr Pediat MS, Stony Brook, NY USA. [Pohl, Daniela] Univ Ottawa, Childrens Hosp Eastern Ontario, Ottawa, ON, Canada. [Rostasy, Kevin] Med Univ Innsbruck, Dept Pediat 4, Div Pediat Neurol & Inborn Errors Metab, A-6020 Innsbruck, Austria. [Tenembaum, Silvia] Natl Pediat Hosp, Buenos Aires, DF, Argentina. [Waubant, Emmanuelle] Univ Calif San Francisco, MS Ctr, San Francisco, CA 94143 USA. [Wassmer, Evangeline] Birmingham Childrens Hosp, Birmingham, W Midlands, England. RP Chitnis, T (reprint author), Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. EM tchitnis@partners.org OI amato, Maria Pia/0000-0003-3325-3760 FU US National MS Society; MS International Federation; Merck-Serono; Biogen Idec; Bayer Schering Pharma; Merck Serono; Teva; Sanofi-Aventis; Ammplimmune; EMD Serono; Novartis; Roche FX The meeting was sponsored by the US National MS Society and the MS International Federation.; T. Chitnis has acted as an advisor/consultant/advisory board member or speaker for Biogen-Idec, Merck-Serono, Novartis, Sanofi-Aventis, and Teva. She has received research support from Merck-Serono. M. Tardieu has acted as an advisor/consultant/advisory board member or speaker for Biogen Idec, Genzyme, and Novartis. M.P. Amato has acted as an advisor/consultant/advisory board member or speaker for Biogen Idec, Bayer Schering Pharma, Merck Serono, and Sanofi-Aventis. She has received research support from Biogen Idec, Bayer Schering Pharma, Merck Serono, Teva, and Sanofi-Aventis. B. Banwell has acted as an advisor/consultant/advisory board member or speaker for Biogen Idec, Merck Serono, Novartis, and Teva. A. Bar-Or has acted as an advisor/consultant/advisory board member or speaker for Amplimmune, Aventis, Bayhill Therapeutics, Biogen Idec, Berlex/Bayer, Diogenix, Eli Lilly, Genentech, Glycominds, GlaxoSmithKline, GJGGF, EMD Serono, Novartis, Ono Pharma, Sanofi-Aventis, Roche, Teva, and Wyeth. He has received research support from Ammplimmune, EMD Serono, Novartis, Roche, and Teva. A. Ghezzi acted as an advisor/consultant/advisory board member or speaker for Actelion, Allergan, Bayer-Schering, Biogen-Dompe, Merck-Serono, Novartis, Sanofi-Aventis, and Teva. A. Kornberg has acted as an advisor/consultant/advisory board member or speaker for Biogen Idec. L. Krupp acted as an advisor/consultant/advisory board member or speaker for Acorda, Axon Advisors Genentech, Bayer, Biogen Idec, EMD-Serono, Novartis, Pfizer, Sanofi-Aventis, and Teva. D. Pohl has acted as an advisor/consultant/advisory board member or speaker for or received honoraria from Bayer-Schering, Biogen-Idec, Merck-Serono, and Teva. K. Rostasy reports no disclosures. S. Tenembaum has acted as an advisor/consultant/advisory board member or speaker for Bayer Schering Pharma, Biogen Idec, Genzyme, Merck Serono, and Teva. E. Waubant has acted as an advisor/consultant/advisory board member or speaker for Actelion, Roche, Sanofi-Aventis, and Teva. She has received research support from Biogen Idec, Roche, and Sanofi-Aventis. E. Wassmer has acted as an advisor/consultant/advisory board member or speaker for Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, Shire, and UCB Pharmaceutical. Go to Neurology.org for full disclosures. NR 27 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 2013 VL 80 IS 12 BP 1161 EP 1168 DI 10.1212/WNL.0b013e318288694e PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 113NF UT WOS:000316674000019 PM 23509048 ER PT J AU Jicha, GA Rentz, DM AF Jicha, Gregory A. Rentz, Dorene M. TI Cognitive and brain reserve and the diagnosis and treatment of preclinical Alzheimer disease SO NEUROLOGY LA English DT Editorial Material C1 [Jicha, Gregory A.] Univ Kentucky, Sanders Brown Ctr Aging, Dept Neurol, Lexington, KY 40506 USA. Univ Kentucky, Alzheimers Dis Ctr, Lexington, KY 40506 USA. [Rentz, Dorene M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Jicha, GA (reprint author), Univ Kentucky, Sanders Brown Ctr Aging, Dept Neurol, Lexington, KY 40506 USA. EM gregory.jicha@uky.edu FU NCATS NIH HHS [UL1TR000117, UL1 TR000117]; NIA NIH HHS [R01AG037497, R01AG019241, 2U01AG024904, P01AG036694, R01AG038651, U01AG010483, P30AG028383, P50AG005134, 5R01AG017935, 2R01AG027435, 7R01AG034554]; NICHD NIH HHS [R01HD064993]; NIMH NIH HHS [5R01MH090291]; NINR NIH HHS [R01NR014189] NR 10 TC 3 Z9 3 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 2013 VL 80 IS 13 BP 1180 EP 1181 DI 10.1212/WNL.0b013e318289714a PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 113OF UT WOS:000316676700011 PM 23486882 ER PT J AU Baca, CB Vickrey, BG Vassar, S Hauptman, JS Dadour, A Oh, T Salamon, N Vinters, HV Sankar, R Mathern, GW AF Baca, Christine B. Vickrey, Barbara G. Vassar, Stefanie Hauptman, Jason S. Dadour, Andrew Oh, Taemin Salamon, Noriko Vinters, Harry V. Sankar, Raman Mathern, Gary W. TI Time to pediatric epilepsy surgery is related to disease severity and nonclinical factors SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; RACIAL DISPARITIES; REFERRAL PATTERNS; INFANTILE SPASMS; UNITED-STATES; CHILDREN; OUTCOMES; SEIZURE; RECOMMENDATIONS; ADOLESCENTS AB Objective: To identify clinical and nonclinical factors associated with time from epilepsy onset to surgical evaluation and treatment among a cohort of children having epilepsy surgery. Methods: Data were abstracted from records of 430 children (younger than 18 years) who had epilepsy neurosurgery at the University of California, Los Angeles from 1986 to 2010. Multivariable Cox proportional hazards models were used to analyze unique associations of clinical severity, pre-referral brain MRI, and sociodemographic characteristics with time to surgery. Results: Shorter time to surgery was associated with active (hazard ratio [HR] 5.67, 95% confidence interval [CI] 3.74-8.70) and successfully treated infantile spasms (HR 2.20, 95% CI 1.63-2.96); daily or more seizures (HR 2.09, 95% CI 1.58-2.76); MRI before referral regardless of imaging findings (HR 1.95, 95% CI 1.47-2.58); private insurance (HR 1.54, 95% CI 1.14-2.09); and Hispanic ethnicity (HR 1.38, 95% CI 1.01-1.87). There were race/ethnicity by insurance interactions (log-rank p = 0.049) with shortest time to surgery for Hispanic children with private insurance. Conclusions: Shorter intervals to surgical treatment were associated with greater epilepsy severity and insurance type, consistent with existing literature. However, associations of shorter times to treatment with having a brain MRI before referral and Hispanic ethnicity were unexpected and warrant further investigation. More knowledgeable referring providers and parents with greater help-seeking capability may explain obtaining an MRI before referral. Shorter intervals to surgery among Hispanic children may relate to the same factors yielding an increased volume of Hispanic children receiving surgery at the University of California, Los Angeles since 2000. Neurology (R) 2013;80:1231-1239 C1 [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie; Vinters, Harry V.; Sankar, Raman] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Neurol, Los Angeles, CA 90095 USA. [Hauptman, Jason S.; Dadour, Andrew; Oh, Taemin; Mathern, Gary W.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Neurosurg, Los Angeles, CA 90095 USA. [Sankar, Raman] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Pediat, Los Angeles, CA 90095 USA. [Mathern, Gary W.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Psychiat & Biobehav Med, Los Angeles, CA 90095 USA. [Sankar, Raman] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Div Pediat Neurol, Los Angeles, CA 90095 USA. [Salamon, Noriko] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Div Neuroradiol, Los Angeles, CA 90095 USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Sect Neuropathol, Los Angeles, CA 90095 USA. [Baca, Christine B.; Vickrey, Barbara G.; Vassar, Stefanie] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. RP Baca, CB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Dept Neurol, Los Angeles, CA 90095 USA. EM cbower@mednet.ucla.edu FU Epilepsy Foundation [213971]; NIH [R01 NS38992, NIA: RC4AG038804, P50 AG16570, P01 AG12435, NS 044378]; NIH/National Institute of Neurological Disorders and Stroke [R37-NS031146-11]; NIH (National Institute of Neurological Disorders and Stroke) [R37-NS031146-11, 1U54 NS081764]; US Veterans Administration Health Services Research and Development Service [NRI-11-126, VA QUERI PRP]; American Heart Association [AHA/PRT 0875133N]; Food and Drug Administration [R01 FD003923]; UCB Pharma; Sunovion; Upsher-Smith; Lundbeck Pharma; Pfizer; [NIH-MH079933] FX This study was supported by Epilepsy Foundation grant 213971 (PI: Dr. Baca) and NIH grant R01 NS38992 (PI: Dr. Mathern).; C. Baca receives salary support from Epilepsy Foundation grant 213971 for this project and also receives research support from the NIH/National Institute of Neurological Disorders and Stroke (R37-NS031146-11). B. Vickrey serves on scientific advisory boards for the Sports Concussion Institute, American Heart Association, and the NIH; receives research support from the NIH (NIA: RC4AG038804; National Institute of Neurological Disorders and Stroke: R37-NS031146-11 and 1U54 NS081764), the US Veterans Administration Health Services Research and Development Service (NRI-11-126 and VA QUERI PRP), the American Heart Association (AHA/PRT 0875133N), and the Food and Drug Administration (R01 FD003923); and is a consultant to EMD Serono Canada. S. Vassar, J. Hauptman, A. Dadour, T. Oh, and N. Salamon report no disclosures relevant to the manuscript. H. Vinters: the H. V. Vinters trust owns shares in and receives dividends from the following makers of drugs and medical equipment: GE, 3M, Pfizer, Teva Pharma, Becton Dickinson, and GlaxoSmithKline PLC. The Vinters laboratory has received research funding in the past from Neuropace, Inc., and currently receives NIH funds for research on stroke and dementia (P50 AG16570, P01 AG12435, NS 044378). R. Sankar serves on scientific advisory boards for and has received honoraria and funding for travel from UCB Pharma, Sunovion, Upsher-Smith, and Lundbeck Pharma; serves on speakers' bureaus for and has received speaker honoraria from UCB, GlaxoSmithKline, and Lundbeck. He receives funding from NIH-MH079933 (coinvestigator) and from Pfizer (Lyrica pediatric partial seizures trial). G. Mathern received research funding from NIH grant R01 NS38992, which partially supported this study and he serves on the Data Management Committee for NeuroPace, Inc. Go to Neurology.org for full disclosures. NR 36 TC 21 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 2013 VL 80 IS 13 BP 1231 EP 1239 DI 10.1212/WNL.0b013e3182897082 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 113OF UT WOS:000316676700020 PM 23468549 ER PT J AU Chick, JFB Chauhan, NR Mullen, KM Kamdar, NV Khurana, B AF Chick, Jeffrey Forris Beecham Chauhan, Nikunj Rashmikant Mullen, Katherine Marie Kamdar, Nirav Vikram Khurana, Bharti TI Teaching NeuroImages: Massive abdominal CSFoma SO NEUROLOGY LA English DT Editorial Material ID PSEUDOCYSTS C1 [Chick, Jeffrey Forris Beecham; Chauhan, Nikunj Rashmikant; Mullen, Katherine Marie; Khurana, Bharti] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kamdar, Nirav Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Chick, JFB (reprint author), Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. EM jchick@partners.org NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 2013 VL 80 IS 13 BP E146 EP E146 DI 10.1212/WNL.0b013e318289705e PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 113OF UT WOS:000316676700006 PM 23530158 ER PT J AU McKenna, BS Brown, GG Drummond, SPA Turner, TH Mano, QR AF McKenna, Benjamin S. Brown, Gregory G. Drummond, Sean P. A. Turner, Travis H. Mano, Quintino R. TI Linking Mathematical Modeling With Human Neuroimaging to Segregate Verbal Working Memory Maintenance Processes From Stimulus Encoding SO NEUROPSYCHOLOGY LA English DT Article DE verbal working memory; functional MRI; mathematical modeling; stimulus degradation; pseudoword length ID SHORT-TERM-MEMORY; LATERAL FRONTAL-CORTEX; PRIMARY VISUAL-CORTEX; PARIETAL CORTEX; WORD-LENGTH; ACTIVATION; FMRI; DORSAL; DISSOCIATION; ORGANIZATION AB Objective: A fundamental dissociation for most working memory (WM) theories involves the separation of sensory-perceptual encoding of stimulus information from the maintenance of this information. The present paper reports tests of this separability hypothesis for visually presented pseudowords at both mathematical and neuroimaging levels of analysis. Method: Levels of analysis were linked by two experimental manipulations-visual degradation and pseudoword length variation-that coupled findings from a mathematical modeling study of WM performed in a separate sample to findings from an event-related functional MRI (fMRI) study reported in the present paper. Results from the mathematical modeling study generated parametric signatures of stimulus encoding and WM rehearsal and displacement. These signatures led to specific predictions about neurophysiological responses to study manipulations in a priori regions of interest (ROI). Results: Results demonstrated predicted dissociations of activation signatures in several ROIs. Significant patterns of brain response mirroring the encode signature were observed only during the task encode interval and only in the visual cortex and posterior fusiform gyrus. In contrast, significant brain response mirroring the rehearsal/displacement signature was observed only in the dorsolateral prefrontal cortex, inferior frontal gyrus, and supramarginal gyro. Conclusions: Present findings support the separability hypothesis insofar as brain regions that underlie sensory-perceptual processes demonstrated encode signatures whereas brain regions that support WM maintenance demonstrated the rehearsal/displacement signature. These results also provide evidence for the utility of combining mathematical modeling with fMRI to integrate information across cognitive and neural levels of analysis. C1 [McKenna, Benjamin S.; Brown, Gregory G.; Drummond, Sean P. A.; Mano, Quintino R.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [McKenna, Benjamin S.; Brown, Gregory G.; Mano, Quintino R.] Vet Affairs San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA USA. [Drummond, Sean P. A.] Vet Affairs San Diego Healthcare Syst, Psychol Serv, San Diego, CA USA. [Turner, Travis H.] Ralph H Johnson Vet Affairs Med Ctr, Psychol Serv, Charleston, SC USA. RP Brown, GG (reprint author), 3350 La Jolla Village Dr,Mail Code 116A, La Jolla, CA 92161 USA. EM gbrown@ucsd.edu FU VA Mental Illness Research, Education, and Clinical Center; National Science Foundation [NSF-0729021] FX This research was supported by a VA Mental Illness Research, Education, and Clinical Center grant to the VA Desert Pacific Health care System; by a National Science Foundation Grant NSF-0729021; and by the VA San Diego Center of Excellence for Stress and Mental Health for infrastructure support. NR 56 TC 6 Z9 6 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAR PY 2013 VL 27 IS 2 BP 243 EP 255 DI 10.1037/a0031515 PG 13 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 111NT UT WOS:000316528700011 PM 23527652 ER PT J AU Grashow, R Spiro, A Taylor, KM Newton, K Shrairman, R Landau, A Sparrow, D Hu, H Weisskopf, M AF Grashow, Rachel Spiro, Avron Taylor, Kathryn M. Newton, Kimberly Shrairman, Ruth Landau, Alexander Sparrow, David Hu, Howard Weisskopf, Marc TI Cumulative lead exposure in community-dwelling adults and fine motor function: Comparing standard and novel tasks in the VA Normative Aging Study SO NEUROTOXICOLOGY LA English DT Article DE Grooved pegboard; Lead; NAS; Fine motor; Visuomotor ID INUIT PRESCHOOL-CHILDREN; BONE LEAD; COGNITIVE FUNCTION; ENVIRONMENTAL LEAD; OLDER-ADULTS; APRAXIC AGRAPHIA; BLOOD LEAD; INTELLECTUAL FUNCTION; PARKINSONS-DISEASE; MANGANESE EXPOSURE AB Background and aims: Lead exposure in children and occupationally exposed adults has been associated with reduced visuomotor and fine motor function. However, associations in environmentally exposed adults remain relatively unexplored. To address this, we examined the association between cumulative lead exposure-as measured by lead in bone-and performance on the grooved pegboard (GP) manual dexterity task, as well as on handwriting tasks using a novel assessment approach, among men in the VA Normative Aging Study (NAS). Methods: GP testing was done with 362 NAS participants, and handwriting assessment with 328, who also had tibia and patella lead measurements made with K-X-Ray Fluorescence (KXRF). GP scores were time (s) to complete the task with the dominant hand. The handwriting assessment approach assessed the production of signature and cursive lowercase 1 and m letter samples. Signature and lm task scores reflect consistency in repeated trials. We used linear regression to estimate associations and 95% confidence intervals (CI) with adjustment for age, smoking, education, income and computer experience. A backward elimination algorithm was used in the subset with both GP and handwriting assessment to identify variables predictive of each outcome. Results: The mean (SD) participant age was 69.1 (7.2) years; mean patella and tibia concentrations were 25.0 (20.7) mu g/g and 19.2 (14.6) mu g/g, respectively. In multivariable-adjusted analyses, GP performance was associated with tibia (beta per 15 mu g/g bone = 4.66, 95% CI: 1.73, 7.58, p = 0.002) and patella (beta per 20 mu g/g = 3.93, 95% CI: 1.11, 6.76, p = 0.006). In multivariable adjusted models of handwriting production, only the lm-pattern task showed a significant association with tibia (beta per 15 mu g/g bone = 1.27, 95% CI: 0.24, 2.29, p = 0.015), such that Im pattern production was more stable with increasing lead exposure. GP and handwriting scores were differentially sensitive to education, smoking, computer experience, financial stability, income and alcohol consumption. Conclusions: Long-term cumulative environmental lead exposure was associated with deficits in GP performance, but not handwriting production. Higher lead appeared to be associated with greater consistency on the lm task. Lead sensitivity differences could suggest that lead affects neural processing speed rather than motor function per se, or could result from distinct brain areas involved in the execution of different motor tasks. (C) 2013 Elsevier Inc. All rights reserved. C1 [Grashow, Rachel; Taylor, Kathryn M.; Newton, Kimberly; Weisskopf, Marc] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Spiro, Avron; Sparrow, David] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, Avron; Sparrow, David] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Spiro, Avron; Sparrow, David] Boston Univ, Sch Med, Boston, MA 02118 USA. [Shrairman, Ruth; Landau, Alexander] VeriFax Corp, Boulder, CO USA. [Hu, Howard] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. RP Grashow, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, 401 Pk Dr,3rd Floor, Boston, MA 02215 USA. EM rgrashow@hsph.harvard.edu OI Spiro III, Avron/0000-0003-4080-8621; Hu, Howard/0000-0002-3676-2707 FU NIH; NIH [T32-ES07069, SBIR-NS037290, R01-ES005257, P30-E5000002, R01-ES010798, K01-ES012653]; VA Clinical Science Research; Clinical Science Research and Development Service of the US Department of Veterans Affairs; National Institutes of Health [R01-AA08941, R01-AG13006, R01-AG14345, R01-AG18436, 5-P42-ES05947]; US Department of Agriculture, Agricultural Research Service [53-K06-510]; Cooperative Studies Program/ERIC; US Department of Veterans Affairs FX The development of the Neuroskill device was funded in part by a NIH Small Business Innovation Award to VeriFax Corporation. The Neuroskill technology was conceived and developed by R. Shrairman and A. Landau, who are the President and Vice President for Research & Development of VeriFax, respectively. The other authors have no conflicts of interest to report.; The study was supported by NIH grants T32-ES07069, SBIR-NS037290, R01-ES005257, P30-E5000002 and R01-ES010798. Dr. Weisskopf was supported by NIH grant K01-ES012653. Both Dr. Spiro and Dr. Sparrow were supported by a VA Clinical Science Research 82 Development Merit Review and Research Career Scientist awards.; The Cognition and Health in Aging Men Project (CHAMP) is supported by the Clinical Science Research and Development Service of the US Department of Veterans Affairs, the National Institutes of Health (grants R01-AA08941, R01-AG13006, R01-AG14345, R01-AG18436, 5-P42-ES05947), and the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510).; The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). NR 63 TC 8 Z9 8 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2013 VL 35 BP 154 EP 161 DI 10.1016/j.neuro.2013.01.005 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 114XV UT WOS:000316777200018 PM 23370289 ER PT J AU Wylie, B AF Wylie, Blair TI Score Zero Making Stillbirths Count SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. RP Wylie, B (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 55 Fruit St, Boston, MA 02114 USA. EM bwylie@partners.org NR 9 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2013 VL 121 IS 3 BP 651 EP 653 DI 10.1097/AOG.0b013e3182830ac2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 112QN UT WOS:000316607600022 PM 23635630 ER PT J AU Lee, MS Mamon, HJ Hong, TS Choi, NC Fidias, PM Kwak, EL Meyerhardt, JA Ryan, DP Bueno, R Donahue, DM Jaklitsch, MT Lanuti, M Rattner, DW Fuchs, CS Enzinger, PC AF Lee, Michael S. Mamon, Harvey J. Hong, Theodore S. Choi, Noah C. Fidias, Panagiotis M. Kwak, Eunice L. Meyerhardt, Jeffrey A. Ryan, David P. Bueno, Raphael Donahue, Dean M. Jaklitsch, Michael T. Lanuti, Michael Rattner, David W. Fuchs, Charles S. Enzinger, Peter C. TI Preoperative Cetuximab, Irinotecan, Cisplatin, and Radiation Therapy for Patients With Locally Advanced Esophageal Cancer SO ONCOLOGIST LA English DT Article DE Cetuximab; Esophageal cancer; EGFR; Chemoradiation ID GROWTH-FACTOR RECEPTOR; PLUS CISPLATIN; PHASE-II; NEOADJUVANT CHEMORADIOTHERAPY; ADENOCARCINOMA; RADIOTHERAPY; TRIAL; AMPLIFICATION; CHEMOTHERAPY; CARCINOMA AB Purpose. To determine the efficacy and toxicity of weekly neoadjuvant cetuximab combined with irinotecan, cisplatin, and radiation therapy in patients with locally advanced esophageal or gastroesophageal junction cancer. Methods and Materials. Patients with stage IIA-IVA esophageal or gastroesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received weekly cetuximab on weeks 0-8 and irinotecan and cisplatin on weeks 1, 2, 4, and 5, with concurrent radiotherapy (50.4 Gy on weeks 1-6), followed by surgical resection. Results. In the first stage, 17 patients were enrolled, 16 of whom had adenocarcinoma. Because of a low pathologic complete response (pCR) rate in this cohort, the trial was discontinued for patients with adenocarcinoma but squamous cell carcinoma patients continued to be enrolled; two additional patients were enrolled before the study was closed as a result of poor accrual. Of the 19 patients enrolled, 18 patients proceeded to surgery, and 16 patients underwent an R0 resection. Three patients (16%) had a pCR. The median progression-free survival interval was 10 months, and the median overall survival duration was 31 months. Severe neutropenia occurred in 47% of patients, and severe diarrhea occurred in 47% of patients. One patient died preoperatively from sepsis, and one patient died prior to hospital discharge following surgical resection. Conclusions. This schedule of cetuximab in combination with irinotecan, cisplatin, and radiation therapy was toxic and did not achieve a sufficient pCR rate in patients with localized esophageal adenocarcinoma to undergo further evaluation. The Oncologist 2013;18:281-287 C1 [Lee, Michael S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bueno, Raphael; Jaklitsch, Michael T.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Mamon, Harvey J.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mamon, Harvey J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hong, Theodore S.; Choi, Noah C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Fidias, Panagiotis M.; Kwak, Eunice L.; Ryan, David P.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Donahue, Dean M.; Lanuti, Michael; Rattner, David W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Enzinger, Peter C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lee, Michael S.; Mamon, Harvey J.; Hong, Theodore S.; Choi, Noah C.; Fidias, Panagiotis M.; Kwak, Eunice L.; Meyerhardt, Jeffrey A.; Ryan, David P.; Bueno, Raphael; Donahue, Dean M.; Jaklitsch, Michael T.; Lanuti, Michael; Rattner, David W.; Fuchs, Charles S.; Enzinger, Peter C.] Harvard Univ, Sch Med, Boston, MA USA. RP Enzinger, PC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM peter_enzinger@dfci.harvard.edu FU Bristol-Myers-Squibb; National Institutes of Health [P50-CA127003]; Novartis; Castle Bioscience FX Supported by Bristol-Myers-Squibb and the National Institutes of Health (grant P50-CA127003).; Theodore S. Hong: Illumina (C/A); Novartis (RF); Panagiotis M. Fidias: Genentech (C/A); Raphael Bueno: Exosome Inc. (C/A); Covidien Inc. Device Company (H); Castle Bioscience (RF); David W. Rattner: Olympus Medical (C/A); Charles S. Fuchs: Bristol Myers Squibb, Amgen, Genentech, Metamark Genetics, Sanofi, Bayer (C/A); Peter C. Enzinger: Genentech/Roche, Sanofi-Aventis, Boehringer-Ingelheim (C/A); Other: Data safety monitoring board: Taiho. NR 22 TC 18 Z9 23 U1 1 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAR PY 2013 VL 18 IS 3 BP 281 EP 287 DI 10.1634/theoncologist.2012-0208 PG 7 WC Oncology SC Oncology GA 115AE UT WOS:000316783300009 PM 23429739 ER PT J AU Hanna, GJ Haddad, RI Lorch, JH AF Hanna, Glenn J. Haddad, Robert I. Lorch, Jochen H. TI Induction Chemotherapy for Locoregionally Advanced Head and Neck Cancer: Past, Present, Future? SO ONCOLOGIST LA English DT Article ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; PHASE-III TRIAL; ADVANCED LARYNGEAL-CANCER; UNRESECTABLE HEAD; RANDOMIZED-TRIAL; ONCOLOGY-GROUP; FINAL REPORT; CISPLATIN; DOCETAXEL AB The treatment of patients with locoregionally advanced squamous cell cancer of the head and neck is still evolving. Induction chemotherapy (IC) is widely used in this patient population and it is unclear how to best incorporate IC into multimodality treatment. Recently, the results of two randomized clinical trials were presented (the PARADIGM and Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer trials), which showed no demonstrable benefit of IC followed by concurrent chemoradiation over concurrent chemoradiotherapy alone. However, a lower rate of distant metastatic disease was noted, suggesting that patients who are at high risk for metastatic disease may benefit from IC. This review summarizes how IC has evolved over the years, provides an update of recent developments, and discusses how IC may develop in the future. The Oncologist 2013;18:288-293 C1 [Hanna, Glenn J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Haddad, Robert I.; Lorch, Jochen H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lorch, JH (reprint author), 450Brookline Ave,SW430, Boston, MA 02215 USA. EM Jochen_Lorch@dfci.harvard.edu FU Boehringer Ingelheim; Adler; Novartis FX Robert I. Haddad: Boehringer Ingelheim, Adler (RF); Jochen H. Lorch: Novartis (RF). The other author indicated no financial relationships. NR 34 TC 15 Z9 16 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAR PY 2013 VL 18 IS 3 BP 288 EP 293 DI 10.1634/theoncologist.2012-0286 PG 6 WC Oncology SC Oncology GA 115AE UT WOS:000316783300010 PM 23442306 ER PT J AU Limaye, SA Posner, MR Krane, JF Fonfria, M Lorch, JH Dillon, DA Shreenivas, AV Tishler, RB Haddad, RI AF Limaye, Sewanti A. Posner, Marshall R. Krane, Jeffrey F. Fonfria, Maria Lorch, Jochen H. Dillon, Deborah A. Shreenivas, Aditya V. Tishler, Roy B. Haddad, Robert I. TI Trastuzumab for the Treatment of Salivary Duct Carcinoma SO ONCOLOGIST LA English DT Article DE Salivary duct cancer; Chemotherapy; Targeted therapy ID BREAST-CANCER; GLAND CARCINOMAS; THERAPY; EXPRESSION; OVEREXPRESSION; CHEMOTHERAPY; PROTEIN; HER-2 AB Objectives. Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high mortality and poor response to treatment. A significant fraction of SDCs are HER2 positive. This retrospective review examines HER2 testing in SDC and the outcome of trastuzumab-based therapy in adjuvant and palliative settings. Methods. A total of 13 patients with SDC and HER2/neu expression by immunohistochemistry of 1-3+ were treated with trastuzumab in adjuvant (n = 8) or palliative (n = 5) setting. Adjuvant therapy consisted of concurrent radiation and chemotherapy with weekly paclitaxel, carboplatin, and trastuzumab (TCH) for 6 weeks followed by TCH for 12 weeks and trastuzumab alone for 1 year. Palliative treatment for metastatic disease consisted of TCH every 3 weeks for 6 cycles followed by trastuzumab for variable time periods with or without second-line chemotherapy for progression. All patients had fluorescence in situ hybridization testing for HER2/neu gene amplification. Results. The median duration of follow-up was 27 months (range: 8 - 48 months). In all, 62% of adjuvant patients (5/8) had no evidence of disease more than 2 years from completion of therapy. All patients with metastatic disease (5/5 patients) responded to treatment with TCH. One patient achieved a complete response and remains with no evidence of disease 52 months after initiation of TCH. The median duration of response was 18 months (range: 8 -52 months). Conclusion. HER2/neu positivity and treatment with trastuzumab correlated well with long-term survival and response in our patients. Based on this data, we propose that HER2/neu status be examined routinely in all patients with SDCs and the treatment be directed accordingly. The Oncologist 2013; 18: 294-300 C1 [Limaye, Sewanti A.; Fonfria, Maria; Lorch, Jochen H.; Shreenivas, Aditya V.; Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tishler, Roy B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Tishler, Roy B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Posner, Marshall R.] Mt Sinai Sch Med, Dept Med Oncol, New York, NY USA. [Krane, Jeffrey F.; Dillon, Deborah A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Limaye, SA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SW 430, Boston, MA 02115 USA. EM sewantia_limaye@dfci.harvard.edu FU Head and Neck Cancer Research Fund at the Dana-Farber Cancer Institute FX This study was supported by the Head and Neck Cancer Research Fund at the Dana-Farber Cancer Institute. We thank Mei Zheng and Krishan Taneja for expert technical assistance with immunohistochemistry and fluorescence in situ hybridization, respectively. NR 28 TC 35 Z9 36 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD MAR PY 2013 VL 18 IS 3 BP 294 EP 300 DI 10.1634/theoncologist.2012-0369 PG 7 WC Oncology SC Oncology GA 115AE UT WOS:000316783300011 PM 23429737 ER PT J AU Myers, LC Sun, PL Brennan, LL London, WB Guinan, EC AF Myers, Laura C. Sun, Pengling Brennan, Lisa L. London, Wendy B. Guinan, Eva C. TI Effect of Weight on Outcomes of Children Undergoing Hematopoietic Cell Transplantation SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE bone marrow transplant; children; obesity ID HIGH-DOSE CHEMOTHERAPY; BODY-MASS INDEX; OBESITY; ADOLESCENTS; OVERWEIGHT; COMPLICATIONS; PREVALENCE; PREDICTORS; LYMPHOMA; DISEASES AB Chemotherapy dosing in hematopoietic cell therapy (HCT) conditioning regimens is based on patient weight. We hypothesized that potential underdosing or overdosing of patients with significant deviation of weight from normal might alter HCT outcomes, such as early mortality, overall or organ-specific toxicity, and/or relapse. We therefore conducted a retrospective analysis of 400 children between the ages of 2 and 18 years who underwent HCT for malignant or nonmalignant disease at Boston Children's Hospital over a 10-year period. Using the Centers for Disease Control and Prevention standard weight classification schema, we found no evidence to suggest a difference in survival or in time to engraftment or in relapse in patients with malignant disease. In the subgroups of patients either receiving autologous HCT or with underlying malignancy, combined overweight and obese patients had a higher rate of any organ, but not organ-specific, Grade 3-5 toxicity compared with the normal weight group. The study was not powered to detect a difference between underweight and normal weight patients. These data suggest that multiple outcome measures over the first year after HCT are unaffected by weight. C1 [Myers, Laura C.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Sun, Pengling; London, Wendy B.; Guinan, Eva C.] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Sun, Pengling; London, Wendy B.; Guinan, Eva C.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. [Brennan, Lisa L.; Guinan, Eva C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Eva_Guinan@DFCI.Harvard.edu RI Sun, Pengling/G-1403-2011 FU American Society for Hematology; G. Greene Foundation FX This project was funded by the American Society for Hematology Trainee Research Grant and the G. Greene Foundation. NR 30 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PD MAR PY 2013 VL 30 IS 2 BP 116 EP 130 DI 10.3109/08880018.2012.743201 PG 15 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 112BS UT WOS:000316567400007 PM 23189973 ER PT J AU Couch, FJ Wang, XS McGuffog, L Lee, A Olswold, C Kuchenbaecker, KB Soucy, P Fredericksen, Z Barrowdale, D Dennis, J Gaudet, MM Dicks, E Kosel, M Healey, S Sinilnikova, OM Lee, A Bacot, F Vincent, D Hogervorst, FBL Peock, S Stoppa-Lyonnet, D Jakubowska, A Radice, P Schmutzler, RK Domchek, SM Piedmonte, M Singer, CF Friedman, E Thomassen, M Hansen, TVO Neuhausen, SL Szabo, CI Blanco, I Greene, MH Karlan, BY Garber, J Phelan, CM Weitzel, JN Montagna, M Olah, E Andrulis, IL Godwin, AK Yannoukakos, D Goldgar, DE Caldes, T Nevanlinna, H Osorio, A Terry, MB Daly, MB van Rensburg, EJ Hamann, U Ramus, SJ Toland, AE Caligo, MA Olopade, OI Tung, N Claes, K Beattie, MS Southey, MC Imyanitov, EN Tischkowitz, M Janavicius, R John, EM Kwong, A Diez, O Balmana, J Barkardottir, RB Arun, BK Rennert, G Teo, SH Ganz, PA Campbell, I van der Hout, AH van Deurzen, CHM Seynaeve, C Garcia, EBG van Leeuwen, FE Meijers-Heijboer, HEJ Gille, JJP Ausems, MGEM Blok, MJ Ligtenberg, MJL Rookus, MA Devilee, P Verhoef, S van Os, TAM Wijnen, JT Frost, D Ellis, S Fineberg, E Platte, R Evans, DG Izatt, L Eeles, RA Adlard, J Eccles, DM Cook, J Brewer, C Douglas, F Hodgson, S Morrison, PJ Side, LE Donaldson, A Houghton, C Rogers, MT Dorkins, H Eason, J Gregory, H McCann, E Murray, A Calender, A Hardouin, A Berthet, P Delnatte, C Nogues, C Lasset, C Houdayer, C Leroux, D Rouleau, E Prieur, F Damiola, F Sobol, H Coupier, I Venat-Bouvet, L Castera, L Gauthier-Villars, M Leone, M Pujol, P Mazoyer, S Bignon, YJ Zlowocka-Perlowska, E Gronwald, J Lubinski, J Durda, K Jaworska, K Huzarski, T Spurdle, AB Viel, A Peissel, B Bonanni, B Melloni, G Ottini, L Papi, L Varesco, L Tibiletti, MG Peterlongo, P Volorio, S Manoukian, S Pensotti, V Arnold, N Engel, C Deissler, H Gadzicki, D Gehrig, A Kast, K Rhiem, K Meindl, A Niederacher, D Ditsch, N Plendl, H Preisler-Adams, S Engert, S Sutter, C Varon-Mateeva, R Wappenschmidt, B Weber, BHF Arver, B Stenmark-Askmalm, M Loman, N Rosenquist, R Einbeigi, Z Nathanson, KL Rebbeck, TR Blank, SV Cohn, DE Rodriguez, GC Small, L Friedlander, M Bae-Jump, VL Fink-Retter, A Rappaport, C Gschwantler-Kaulich, D Pfeiler, G Tea, MK Lindor, NM Kaufman, B Paluch, SS Laitman, Y Skytte, AB Gerdes, AM Pedersen, IS Moeller, ST Kruse, TA Jensen, UB Vijai, J Sarrel, K Robson, M Kauff, N Mulligan, AM Glendon, G Ozcelik, H Ejlertsen, B Nielsen, FC Jonson, L Andersen, MK Ding, YC Steele, L Foretova, L Teule, A Lazaro, C Brunet, J Pujana, MA Mai, PL Loud, JT Walsh, C Lester, J Orsulic, S Narod, SA Herzog, J Sand, SR Tognazzo, S Agata, S Vaszko, T Weaver, J Stavropoulou, AV Buys, SS Romero, A de la Hoya, M Aittomaki, K Muranen, TA Duran, M Chung, WK Lasa, A Dorfling, CM Miron, A Benitez, J Senter, L Huo, DZ Chan, SB Sokolenko, AP Chiquette, J Tihomirova, L Friebel, TM Agnarsson, BA Lu, KH Lejbkowicz, F James, PA Hall, P Dunning, AM Tessier, D Cunningham, J Slager, SL Wang, C Hart, S Stevens, K Simard, J Pastinen, T Pankratz, VS Offit, K Easton, DF Chenevix-Trench, G Antoniou, AC AF Couch, Fergus J. Wang, Xianshu McGuffog, Lesley Lee, Andrew Olswold, Curtis Kuchenbaecker, Karoline B. Soucy, Penny Fredericksen, Zachary Barrowdale, Daniel Dennis, Joe Gaudet, Mia M. Dicks, Ed Kosel, Matthew Healey, Sue Sinilnikova, Olga M. Lee, Adam Bacot, Francois Vincent, Daniel Hogervorst, Frans B. L. Peock, Susan Stoppa-Lyonnet, Dominique Jakubowska, Anna Radice, Paolo Schmutzler, Rita Katharina Domchek, Susan M. Piedmonte, Marion Singer, Christian F. Friedman, Eitan Thomassen, Mads Hansen, Thomas V. O. Neuhausen, Susan L. Szabo, Csilla I. Blanco, Ignacio Greene, Mark H. Karlan, Beth Y. Garber, Judy Phelan, Catherine M. Weitzel, Jeffrey N. Montagna, Marco Olah, Edith Andrulis, Irene L. Godwin, Andrew K. Yannoukakos, Drakoulis Goldgar, David E. Caldes, Trinidad Nevanlinna, Heli Osorio, Ana Terry, Mary Beth Daly, Mary B. van Rensburg, Elizabeth J. Hamann, Ute Ramus, Susan J. Toland, Amanda Ewart Caligo, Maria A. Olopade, Olufunmilayo I. Tung, Nadine Claes, Kathleen Beattie, Mary S. Southey, Melissa C. Imyanitov, Evgeny N. Tischkowitz, Marc Janavicius, Ramunas John, Esther M. Kwong, Ava Diez, Orland Balmana, Judith Barkardottir, Rosa B. Arun, Banu K. Rennert, Gad Teo, Soo-Hwang Ganz, Patricia A. Campbell, Ian van der Hout, Annemarie H. van Deurzen, Carolien H. M. Seynaeve, Caroline Garcia, Encarna B. Gomez van Leeuwen, Flora E. Meijers-Heijboer, Hanne E. J. Gille, Johannes J. P. Ausems, Margreet G. E. M. Blok, Marinus J. Ligtenberg, Marjolijn J. L. Rookus, Matti A. Devilee, Peter Verhoef, Senno van Os, Theo A. M. Wijnen, Juul T. Frost, Debra Ellis, Steve Fineberg, Elena Platte, Radka Evans, D. Gareth Izatt, Louise Eeles, Rosalind A. Adlard, Julian Eccles, Diana M. Cook, Jackie Brewer, Carole Douglas, Fiona Hodgson, Shirley Morrison, Patrick J. Side, Lucy E. Donaldson, Alan Houghton, Catherine Rogers, Mark T. Dorkins, Huw Eason, Jacqueline Gregory, Helen McCann, Emma Murray, Alex Calender, Alain Hardouin, Agnes Berthet, Pascaline Delnatte, Capucine Nogues, Catherine Lasset, Christine Houdayer, Claude Leroux, Dominique Rouleau, Etienne Prieur, Fabienne Damiola, Francesca Sobol, Hagay Coupier, Isabelle Venat-Bouvet, Laurence Castera, Laurent Gauthier-Villars, Marion Leone, Melanie Pujol, Pascal Mazoyer, Sylvie Bignon, Yves-Jean Zlowocka-Perlowska, Elzbieta Gronwald, Jacek Lubinski, Jan Durda, Katarzyna Jaworska, Katarzyna Huzarski, Tomasz Spurdle, Amanda B. Viel, Alessandra Peissel, Bernard Bonanni, Bernardo Melloni, Giulia Ottini, Laura Papi, Laura Varesco, Liliana Tibiletti, Maria Grazia Peterlongo, Paolo Volorio, Sara Manoukian, Siranoush Pensotti, Valeria Arnold, Norbert Engel, Christoph Deissler, Helmut Gadzicki, Dorothea Gehrig, Andrea Kast, Karin Rhiem, Kerstin Meindl, Alfons Niederacher, Dieter Ditsch, Nina Plendl, Hansjoerg Preisler-Adams, Sabine Engert, Stefanie Sutter, Christian Varon-Mateeva, Raymonda Wappenschmidt, Barbara Weber, Bernhard H. F. Arver, Brita Stenmark-Askmalm, Marie Loman, Niklas Rosenquist, Richard Einbeigi, Zakaria Nathanson, Katherine L. Rebbeck, Timothy R. Blank, Stephanie V. Cohn, David E. Rodriguez, Gustavo C. Small, Laurie Friedlander, Michael Bae-Jump, Victoria L. Fink-Retter, Anneliese Rappaport, Christine Gschwantler-Kaulich, Daphne Pfeiler, Georg Tea, Muy-Kheng Lindor, Noralane M. Kaufman, Bella Paluch, Shani Shimon Laitman, Yael Skytte, Anne-Bine Gerdes, Anne-Marie Pedersen, Inge Sokilde Moeller, Sanne Traasdahl Kruse, Torben A. Jensen, Uffe Birk Vijai, Joseph Sarrel, Kara Robson, Mark Kauff, Noah Mulligan, Anna Marie Glendon, Gord Ozcelik, Hilmi Ejlertsen, Bent Nielsen, Finn C. Jonson, Lars Andersen, Mette K. Ding, Yuan Chun Steele, Linda Foretova, Lenka Teule, Alex Lazaro, Conxi Brunet, Joan Angel Pujana, Miquel Mai, Phuong L. Loud, Jennifer T. Walsh, Christine Lester, Jenny Orsulic, Sandra Narod, Steven A. Herzog, Josef Sand, Sharon R. Tognazzo, Silvia Agata, Simona Vaszko, Tibor Weaver, Joellen Stavropoulou, Alexandra V. Buys, Saundra S. Romero, Atocha de la Hoya, Miguel Aittomaki, Kristiina Muranen, Taru A. Duran, Mercedes Chung, Wendy K. Lasa, Adriana Dorfling, Cecilia M. Miron, Alexander Benitez, Javier Senter, Leigha Huo, Dezheng Chan, Salina B. Sokolenko, Anna P. Chiquette, Jocelyne Tihomirova, Laima Friebel, Tara M. Agnarsson, Bjarni A. Lu, Karen H. Lejbkowicz, Flavio James, Paul A. Hall, Per Dunning, Alison M. Tessier, Daniel Cunningham, Julie Slager, Susan L. Wang, Chen Hart, Steven Stevens, Kristen Simard, Jacques Pastinen, Tomi Pankratz, Vernon S. Offit, Kenneth Easton, Douglas F. Chenevix-Trench, Georgia Antoniou, Antonis C. CA KConFab Investigators SWE-BRCA Ontario Canc Genetics Network HEBON EMBRACE GEMO Study Collaborators BCFR CIMBA TI Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk SO PLOS GENETICS LA English DT Article ID COMMON VARIANTS; SUSCEPTIBILITY ALLELES; GENETIC-VARIANTS; MODIFIERS; INVESTIGATORS; POPULATION; CONSORTIUM; SELECTION; SUBTYPES; ZNF365 AB BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. C1 [Couch, Fergus J.; Wang, Xianshu; Cunningham, Julie; Stevens, Kristen] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Couch, Fergus J.; Cunningham, Julie; Stevens, Kristen] Mayo Clin, Rochester, MN USA. [McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline B.; Barrowdale, Daniel; Dennis, Joe; Dicks, Ed; Peock, Susan; Frost, Debra; Fineberg, Elena; Platte, Radka; Easton, Douglas F.; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Olswold, Curtis; Fredericksen, Zachary; Kosel, Matthew; Slager, Susan L.; Wang, Chen; Hart, Steven; Pankratz, Vernon S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Soucy, Penny; Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Soucy, Penny; Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia. [Sinilnikova, Olga M.; Calender, Alain; Leone, Melanie] Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, Ctr Leon Berard, Lyon, France. 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[Morrison, Patrick J.] Belfast Hlth & Social Care Trust, Northern Ireland Reg Genet Ctr, Belfast, Antrim, North Ireland. [Morrison, Patrick J.] Queens Univ Belfast, Dept Med Genet, Belfast, Antrim, North Ireland. [Side, Lucy E.] Great Ormond St Hosp Sick Children, North East Thames Reg Genet Serv, London WC1N 3JH, England. [Side, Lucy E.] UCL, Inst Womens Hlth, London, England. [Donaldson, Alan] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England. [Houghton, Catherine] Liverpool Womens NHS Fdn Trust, Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England. [Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales. [Dorkins, Huw] Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England. [Eason, Jacqueline] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England. [Gregory, Helen] NHS Grampian, North Scotland Reg Genet Serv, Aberdeen, Scotland. 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RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. EM couch.fergus@mayo.edu; Antonis@srl.cam.ac.uk RI Andrulis, Irene/E-7267-2013; Ditsch, Nina/F-6267-2014; James, Paul/G-2943-2014; friedlander, michael/G-3490-2013; Leroux, Dominique/G-7309-2014; Teo, Soo-hwang/H-2353-2014; Osorio, Ana/I-4324-2014; Toland, Amanda/E-4202-2011; Joseph, Vijai/J-9158-2013; Radice, Paolo/O-3119-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Blanco, Ignacio/D-2565-2013; Spurdle, Amanda/A-4978-2011; Arnold, Norbert/E-3012-2010; pujana, Miguel Angel/N-3127-2014; Jakubowska, Anna/O-8050-2014; campbell, Ian/F-6006-2011; montagna, marco/E-2225-2012; Ligtenberg, Marjolijn/N-9666-2013; Wang, Chen/B-3244-2011; Sokolenko, Anna/G-3123-2013; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; OI Dunning, Alison Margaret/0000-0001-6651-7166; ROMERO, ATOCHA/0000-0002-1634-7397; Muranen, Taru/0000-0002-5895-1808; VENAT-BOUVET, Laurence/0000-0002-0716-2550; Evans, Gareth/0000-0002-8482-5784; friedlander, michael/0000-0002-6488-0604; Osorio, Ana/0000-0001-8124-3984; Joseph, Vijai/0000-0002-7933-151X; Blanco, Ignacio/0000-0002-7414-7481; Ramus, Susan/0000-0003-0005-7798; Papi, Laura/0000-0003-4552-9517; Brunet, Joan/0000-0003-1945-3512; Kauff, Noah/0000-0001-7242-6156; Nevanlinna, Heli/0000-0002-0916-2976; Yannoukakos, Drakoulis/0000-0001-7509-3510; Rappaport-Fuerhauser, Christine/0000-0002-6820-0020; Spurdle, Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939; Barton, David E/0000-0002-2031-9719; Dite, Gillian/0000-0002-2448-2548; Robson, Mark/0000-0002-3109-1692; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Devilee, Peter/0000-0002-8023-2009; Arnold, Norbert/0000-0003-4523-8808; pujana, Miguel Angel/0000-0003-3222-4044; montagna, marco/0000-0002-4929-2150; Ligtenberg, Marjolijn/0000-0003-1290-1474; Wang, Chen/0000-0003-2638-3081; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Dennis, Joe/0000-0003-4591-1214; Janavicius, Ramunas/0000-0002-3773-8485 FU NIH [CA128978, P30 CA033752, R01CA74415, 1R01 CA149429-01]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S. Department of Defense Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen Foundation for the Cure; Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]; European Commission [223175 (HEALTH-F2-2009-223175)]; National Cancer Institute, National Institutes of Health under RFA [CA-06-503]; Breast Cancer Family Registry (BCFR); Cancer Care Ontario [U01 CA69467]; Cancer Prevention Institute of California [U01 CA69417]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; National Institutes of Health [P01 CA16094, R01 CA22435]; National Center for Research Resources; National Center for Advancing Translational Sciences, NIH [UL1 RR025764]; National Cancer Institute [P30 CA042014, RC4A153828, CA 27469, CA 37517, CA 101165]; Research Council of Lithuania [LIG-19/2010]; Lithuania (BFBOCC-LT); Hereditary Cancer Association (Paveldimo vezio asociacija); LSC [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Cancer Association of South Africa (CANSA); Morris and Horowitz Families Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation (FMMA); Office of the Director, National Institutes of Health; Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"); Italian Association for Cancer Research (AIRC) [IG 8713]; Italian Minitry of Health; Italian Ministry of Education, University and Research, Centro di Ascolto Donne Operate al Seno (CAOS) association; DKFZ; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; NWO [91109024]; Pink Ribbon grant [110005]; BBMRI [CP46/NWO]; NIHR; Royal Marsden NHS Foundation Trust; University of Kansas Cancer Center; 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!"; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Intramural Research Program, NCI, NIH; RETICC [06/0020/0021]; FIS [09/00859]; Instituto de Salud Carlos III; Spanish Ministry of Economy and Competitivity; European Regional Development Fund (ERDF); Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation; Hong Kong Hereditary Breast Cancer Family Registry; Dr. Ellen Li Charitable Foundation, Hong Kong; Hungarian Research [HU0115/NA/2008-3/OP-9]; Asociacion Espanola Contra el Cancer; Spanish Health Research Foundation; Ramon Areces Foundation; Carlos III Health Institute; Catalan Health Institute; Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, PI09/02483, PI10/01422, PI10/00748, 2009SGR290, 2009SGR283]; Polish Foundation of Science; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance [019511]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Ministero dell'Istruzione, dell'Universitae della Ricerca; Ministero della Salute [RFPS 2006-5-341353, ACC2/R6.9]; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; Cancer Councils of New South Wales, Tasmania; Cancer Councils of New South Wales, South Australia; Cancer Foundation of Western Australia; NHMRC; Cancer Australia [628333]; Jewish General Hospital; Quebec Ministry of Economic Development, Innovation, and Export Trade; Niehaus Clinical Cancer Genetics Initiative; Andrew Sabin Family Foundation; Lymphoma Foundation; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; Intramural Research Program of the US National Cancer Institute, NIH; Westat, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), NY; Russian Foundation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Royal Society [JP090615]; Ohio State University Comprehensive Cancer Center; Swedish Cancer Society; US National Cancer Institute (NIH/NCI); Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance,; Jonsson Comprehensive Cancer Center Foundation; UCSF Cancer Risk Program; Helen Diller Family Comprehensive Cancer Center; CRUK; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Rooney Family Foundation; Susan G. Komen Foundation for the Cure; Macdonald Family Foundation; Victorian Cancer Agency; Cancer Australia; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; [SAF2010-20493]; [5U01CA113916]; [R01CA140323] FX The study was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341), grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure; Cancer Research UK grants C12292/A11174 and C1287/A10118; the European Commission's Seventh Framework Programme grant agreement 223175 (HEALTH-F2-2009-223175). Breast Cancer Family Registry Studies (BCFR): supported by the National Cancer Institute, National Institutes of Health under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute of California (U01 CA69417), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), and University of Melbourne (U01 CA69638). The Australian BCFR was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. Melissa C. Southey is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. Carriers at FCCC were also identified with support from National Institutes of Health grants P01 CA16094 and R01 CA22435. The New York BCFR was also supported by National Institutes of Health grants P30 CA13696 and P30 ES009089. The Utah BCFR was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH grant UL1 RR025764, and by Award Number P30 CA042014 from the National Cancer Institute. Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC): BFBOCC is partly supported by Lithuania (BFBOCC-LT), Research Council of Lithuania grant LIG-19/2010, 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. BRCA-gene mutations and breast cancer in South African women (BMBSA): BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. Beckman Research Institute of the City of Hope (BRICOH): Susan L. Neuhausen was partially supported by the Morris and Horowitz Families Endowed Professorship. BRICOH was supported by NIH R01CA74415 and NIH P30 CA033752. Copenhagen Breast Cancer Study (CBCS): The CBCS study was supported by the NEYE Foundation. Spanish National Cancer Centre (CNIO): This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena Foundation (FMMA) and SAF2010-20493. City of Hope Cancer Center (COH): The City of Hope Clinical Cancer Genetics Community Research Network is supported by Award Number RC4A153828 (PI: Jeffrey N. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health.; CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella (CONSIT TEAM): CONSIT TEAM was funded by grants from Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"), Italian Association for Cancer Research (AIRC, IG 8713), Italian Minitry of Health (Extraordinary National Cancer Program 2006, "Alleanza contro il Cancro" and "Progetto Tumori Femminili), Italian Ministry of Education, University and Research (Prin 2008) Centro di Ascolto Donne Operate al Seno (CAOS) association 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 '561000'). German Cancer Research Center (DKFZ): The DKFZ study was supported by the DKFZ. The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON): HEBON is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the NWO grant 91109024, the Pink Ribbon grant 110005, and the BBMRI grant CP46/NWO. Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE): EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo 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. Rosalind A. Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Fox Chase Cancer Canter (FCCC): The authors acknowledge support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. Andrew K. Godwin was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC): The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers (GEMO): The GEMO 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. Gynecologic Oncology Group (GOG): This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committtee (CA 101165). Drs. Mark H. Greene and Phuong L. Mai were supported by funding from the Intramural Research Program, NCI, NIH. Hospital Clinico San Carlos (HCSC): HCSC was supported by RETICC 06/0020/0021, FIS research grant 09/00859, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitivity, and the European Regional Development Fund (ERDF). Helsinki Breast Cancer Study (HEBCS): The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, the Nordic Cancer Union, and the Sigrid Juselius Foundation.; Study of Genetic Mutations in Breast and Ovarian Cancer patients in Hong Kong and Asia (HRBCP): HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr. Ellen Li Charitable Foundation, Hong Kong. Molecular Genetic Studies of Breast and Ovarian Cancer in Hungary (HUNBOCS): HUNBOCS was supported by Hungarian Research Grant KTIA-OTKA CK-80745 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. Institut Catala d'Oncologia (ICO): The ICO study was supported by the Asociacion Espanola Contra el Cancer, Spanish Health Research Foundation, Ramon Areces Foundation, Carlos III Health Institute, Catalan Health Institute, and Autonomous Government of Catalonia and contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI09/02483, PI10/01422, PI10/00748, 2009SGR290, and 2009SGR283. International Hereditary Cancer Centre (IHCC): Supported by the Polish Foundation of Science. Katarzyna Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. Iceland Landspitali-University Hospital (ILUH): The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INterdisciplinary HEalth Research Internal Team BReast CAncer susceptibility (INHERIT): INHERIT 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. Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics. Istituto Oncologico Veneto (IOVHBOCS): The IOVHBOCS study was supported by Ministero dell'Istruzione, dell'Universitae della Ricerca and Ministero della Salute ("Progetto Tumori Femminili" and RFPS 2006-5-341353, ACC2/R6.9"). Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab): kConFab is supported by grants from the National Breast Cancer Foundation and 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. Amanda B. Spurdle is an NHMRC Senior Research Fellow. The Clinical Follow Up Study was funded from 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia # 628333. Mayo Clinic (MAYO): 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. McGill University (MCGILL): The McGill Study was supported by Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation, and Export Trade. Memorial Sloan-Kettering Cancer Center (MSKCC): The MSKCC study was supported by Breast Cancer Research Foundation, Niehaus Clinical Cancer Genetics Initiative, Andrew Sabin Family Foundation, and Lymphoma Foundation. Modifier Study of Quantitative Effects on Disease (MODSQUAD): MODSQUAD was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101). Women's College Research Institute, Toronto (NAROD): NAROD was supported by NIH grant: 1R01 CA149429-01. National Cancer Institute (NCI): Drs. Mark H.; Greene and Phuong L. Mai were 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, Rockville, MD. National Israeli Cancer Control Center (NICCC): 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. N. N. Petrov Institute of Oncology (NNPIO): The NNPIO study has been supported by the Russian Foundation for Basic Research (grants 11-04-00227, 12-04-00928, and 12-04-01490), the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780), and through a Royal Society International Joint grant (JP090615). The Ohio State University Comprehensive Cancer Center (OSU-CCG): OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. South East Asian Breast Cancer Association Study (SEABASS): SEABASS is supported by the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM. C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. Sheba Medical Centre (SMC): The SMC study was partially funded through a grant by the Israel Cancer Association and the funding for the Israeli Inherited Breast Cancer Consortium. Swedish Breast Cancer Study (SWE-BRCA): SWE-BRCA collaborators are supported by the Swedish Cancer Society. The University of Chicago Center for Clinical Cancer Genetics and Global Health (UCHICAGO): UCHICAGO is supported by grants from the US National Cancer Institute (NIH/NCI) 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. University of California Los Angeles (UCLA): The UCLA study was supported by the Jonsson Comprehensive Cancer Center Foundation and the Breast Cancer Research Foundation. University of California San Francisco (UCSF): The UCSF study was supported by the UCSF Cancer Risk Program and the Helen Diller Family Comprehensive Cancer Center. United Kingdom Familial Ovarian Cancer Registries (UKFOCR): UKFOCR was supported by a project grant from CRUK to Paul Pharoah. University of Pennsylvania (UPENN): The UPENN study was supported by the National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855), Breast Cancer Research Foundation, Rooney Family Foundation, Susan G. Komen Foundation for the Cure, and the Macdonald Family Foundation. Victorian Familial Cancer Trials Group (VFCTG): The VFCTG study was supported by the Victorian Cancer Agency, Cancer Australia, and National Breast Cancer Foundation. Women's Cancer Research Initiative (WCRI): The WCRI at the Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 85 Z9 87 U1 12 U2 75 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 MAR PY 2013 VL 9 IS 3 AR e1003212 DI 10.1371/journal.pgen.1003212 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA 116EY UT WOS:000316866700002 PM 23544013 ER PT J AU Nickels, S Truong, T Hein, R Stevens, K Buck, K Behrens, S Eilber, U Schmidt, M Haberle, L Vrieling, A Gaudet, M Figueroa, J Schoof, N Spurdle, AB Rudolph, A Fasching, PA Hopper, JL Makalic, E Schmidt, DF Southey, MC Beckmann, MW Ekici, AB Fletcher, O Gibson, L Silva, ID Peto, J Humphreys, MK Wang, J Cordina-Duverger, E Menegaux, F Nordestgaard, BG Bojesen, SE Lanng, C Anton-Culver, H Ziogas, A Bernstein, L Clarke, CA Brenner, H Muller, H Arndt, V Stegmaier, C Brauch, H Bruning, T Harth, V Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Lambrechts, D Smeets, D Neven, P Paridaens, R Flesch-Janys, D Obi, N Wang-Gohrke, S Couch, FJ Olson, JE Vachon, CM Giles, GG Severi, G Baglietto, L Offit, K John, EM Miron, A Andrulis, IL Knight, JA Glendon, G Mulligan, AM Chanock, SJ Lissowska, J Liu, JJ Cox, A Cramp, H Connley, D Balasubramanian, S Dunning, AM Shah, M Trentham-Dietz, A Newcomb, P Titus, L Egan, K Cahoon, EK Rajaraman, P Sigurdson, AJ Doody, MM Guenel, P Pharoah, PDP Schmidt, MK Hall, P Easton, DF Garcia-Closas, M Milne, RL Chang-Claude, J AF Nickels, Stefan Truong, Therese Hein, Rebecca Stevens, Kristen Buck, Katharina Behrens, Sabine Eilber, Ursula Schmidt, Martina Haeberle, Lothar Vrieling, Alina Gaudet, Mia Figueroa, Jonine Schoof, Nils Spurdle, Amanda B. Rudolph, Anja Fasching, Peter A. Hopper, John L. Makalic, Enes Schmidt, Daniel F. Southey, Melissa C. Beckmann, Matthias W. Ekici, Arif B. Fletcher, Olivia Gibson, Lorna Silva, Isabel dos Santos Peto, Julian Humphreys, Manjeet K. Wang, Jean Cordina-Duverger, Emilie Menegaux, Florence Nordestgaard, Borge G. Bojesen, Stig E. Lanng, Charlotte Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Clarke, Christina A. Brenner, Hermann Mueller, Heiko Arndt, Volker Stegmaier, Christa Brauch, Hiltrud Bruening, Thomas Harth, Volker Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Lambrechts, Diether Smeets, Dominiek Neven, Patrick Paridaens, Robert Flesch-Janys, Dieter Obi, Nadia Wang-Gohrke, Shan Couch, Fergus J. Olson, Janet E. Vachon, Celine M. Giles, Graham G. Severi, Gianluca Baglietto, Laura Offit, Kenneth John, Esther M. Miron, Alexander Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Chanock, Stephen J. Lissowska, Jolanta Liu, Jianjun Cox, Angela Cramp, Helen Connley, Dan Balasubramanian, Sabapathy Dunning, Alison M. Shah, Mitul Trentham-Dietz, Amy Newcomb, Polly Titus, Linda Egan, Kathleen Cahoon, Elizabeth K. Rajaraman, Preetha Sigurdson, Alice J. Doody, Michele M. Guenel, Pascal Pharoah, Paul D. P. Schmidt, Marjanka K. Hall, Per Easton, Doug F. Garcia-Closas, Montserrat Milne, Roger L. Chang-Claude, Jenny CA GENICA Network kConFab AOCS Management Grp TI Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MAMMOGRAPHIC DENSITY; 14Q24.1 RAD51L1; HORMONE-THERAPY; POOLED ANALYSIS; TUMOR SUBTYPES; VARIANTS; CONSORTIUM; FGFR2; WOMEN AB Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (P-interaction = 2.4 x 10(-6)) and between CASP8-rs17468277 and alcohol consumption (P-interaction = 3.1 x 10(-4)). Overall, the perallele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank >= 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (P-interaction = 5.3 x 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors. C1 [Nickels, Stefan; Behrens, Sabine; Eilber, Ursula; Vrieling, Alina; Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Truong, Therese; Cordina-Duverger, Emilie; Menegaux, Florence; Guenel, Pascal] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc U1018, Villejuif, France. [Hein, Rebecca] Univ Cologne, PMV Res Grp, Dept Child & Adolescent Psychiat & Psychotherapy, D-50931 Cologne, Germany. [Stevens, Kristen; Olson, Janet E.; Vachon, Celine M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Buck, Katharina] Natl Ctr Tumor Dis, Dept Prevent Oncol, Heidelberg, Germany. [Schmidt, Martina] German Canc Res Ctr, Environm Epidemiol Unit, Heidelberg, Germany. [Haeberle, Lothar; Fasching, Peter A.; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Univ Hosp, D-91054 Erlangen, Germany. [Vrieling, Alina] Radboud Univ Nijmegen Med Ctr, Dept Hlth Evidence, Nijmegen, Netherlands. [Gaudet, Mia] Amer Canc Soc, Epidemiol Res Program, Div Canc Epidemiol, Atlanta, GA 30329 USA. [Figueroa, Jonine; Hall, Per] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Schoof, Nils] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Spurdle, Amanda B.] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Hopper, John L.; Makalic, Enes; Schmidt, Daniel F.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Fletcher, Olivia] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Gibson, Lorna; Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, London WC1, England. [Humphreys, Manjeet K.; Wang, Jean; Easton, Doug F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Nordestgaard, Borge G.; Bojesen, Stig E.] Univ Copenhagen, Copenhagen Gen Populat Study, Herlev Univ Hosp, Copenhagen, Denmark. [Nordestgaard, Borge G.; Bojesen, Stig E.] Univ Copenhagen, Dept Clin Biochem, Herlev Univ Hosp, Copenhagen, Denmark. [Lanng, Charlotte] Univ Copenhagen, Dept Breast Surg, Herlev Univ Hosp, Copenhagen, Denmark. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA. [Clarke, Christina A.; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Clarke, Christina A.; John, Esther M.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Div Epidemiol, Stanford, CA 94305 USA. [Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Ageing Res, Heidelberg, Germany. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany. [Bruening, Thomas] Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med German Social Accid In, Bochum, Germany. [Harth, Volker] Univ Saarland, Med Ctr, Inst & Outpatient Clin Occupat Med, Homburg, Germany. [Harth, Volker] Univ Saarland, Fac Med, Homburg, Germany. [Harth, Volker] Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, Hamburg, Germany. Johanniter Krankenhaus, Dept Internal Med, Evangel Kliniken Bonn gGmbH, Bonn, Germany. Univ Bonn, Inst Pathol, Bonn, Germany. [GENICA Network] German Canc Res Ctr, Heidelberg, Germany. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med, Dept Pathol & Forens Med, Kuopio, Finland. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Bioctr Kuopio, Canc Ctr Eastern Finland, Kuopio, Finland. [Kataja, Vesa] Univ Eastern Finland, Sch Med, Inst Clin Med, Dept Oncol, Kuopio, Finland. [kConFab; AOCS Management Grp] Peter MacCallum Canc Ctr, Kathleen Cuningham Fdn Resesarch Familial Breast, East Melbourne, Australia. [Lambrechts, Diether; Smeets, Dominiek] Katholieke Univ Leuven VIB, Vesalius Res Ctr, Louvain, Belgium. [Neven, Patrick; Paridaens, Robert] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Flesch-Janys, Dieter; Obi, Nadia] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany. [Flesch-Janys, Dieter; Obi, Nadia] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Miron, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA. [Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ontario Canc Genet Network, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Glendon, Gord] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Chanock, Stephen J.; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore. [Cox, Angela; Cramp, Helen; Connley, Dan] Univ Sheffield, Inst Canc Studies, Dept Oncol, Sheffield, S Yorkshire, England. [Balasubramanian, Sabapathy] Univ Sheffield, Acad Unit Surg Oncol, Dept Oncol, Sheffield, S Yorkshire, England. [Dunning, Alison M.; Shah, Mitul; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England. [Trentham-Dietz, Amy; Newcomb, Polly] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Newcomb, Polly] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Titus, Linda] Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Dept Pediat, Dartmouth Med Sch, Lebanon, NH 03766 USA. [Cahoon, Elizabeth K.; Rajaraman, Preetha; Sigurdson, Alice J.; Doody, Michele M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Schmidt, Marjanka K.] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands. [Schmidt, Marjanka K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. [Garcia-Closas, Montserrat] Inst Canc Res, Epidemiol Sect, London SW3 6JB, England. [Garcia-Closas, Montserrat] Inst Canc Res, Genet Sect, London SW3 6JB, England. [Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London, England. [Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Human Canc Genet Programme, Madrid, Spain. RP Nickels, S (reprint author), German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. EM j.chang-claude@dkfz.de RI Verdrengh, Evelien/H-4571-2012; Vrieling, Alina/A-2725-2016; Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; Brenner, Hermann/B-4627-2017; Spurdle, Amanda/A-4978-2011; Andrulis, Irene/E-7267-2013; Ekici, Arif/C-3971-2013; Knight, Julia/A-6843-2012; Garcia-Closas, Montserrat /F-3871-2015; Hartikainen, Jaana/E-6256-2015 OI Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464; Brenner, Hermann/0000-0002-6129-1572; Rudolph, Anja/0000-0001-7520-2035; Spurdle, Amanda/0000-0003-1337-7897; Garcia-Closas, Montserrat /0000-0003-1033-2650; FU Cancer Research UK [C1287/A10118, C1287/A12014, C490/A6187, C490/A10119, C490/A10124]; European Community [223175 (HEALTH-F2-2009-223175)]; European Union COST programme [BM0606]; Fondo de Investigacion Sanitario [PI11/00923]; Australian NHMRC; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); National Cancer Institute, National Institutes of Health under RFA [CA-06-503]; BCFR and Principal Investigators; Cancer Care Ontario [U01 CA69467]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; Cancer Prevention Institute of California [U01 CA69417]; University of Melbourne [U01 CA69638]; Georgetown University Medical Center Informatics Support Center [HHSN261200900010C]; ELAN-Fond of the University Hospital of Erlangen; Cancer Research UK; Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); Fondation de France; French National Institute of Cancer (INCa); National League against Cancer; National Agency for Environmental and Occupational Health and Food Safety (ANSES); National Agency for Research (ANR); Association for Research against Cancer (ARC); Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Herlev Hospital; California Breast Cancer Act of 1993; National Institutes of Health [R01 CA77398]; Lon V Smith Foundation [LVS39420]; California Breast Cancer Research Fund [97-10500]; Baden Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid (Deutsche Krebshilfe); Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany; Deutsche Krebshilfe e.V. [70492, 70-2892-BR I]; Government Funding (EVO) of Kuopio University Hospital; Cancer Fund of North Savo; Finnish Cancer Organizations; Academy of Finland; University of Eastern Finland; National Breast Cancer Foundation; NHMRC; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508, 199600]; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of Tasmania and Cancer Foundation of Western Australia; Stichting tegen Kanker [232-2008, 196-2010]; Hamburg Cancer Society; German Cancer Research Center; NIH [CA122340, CA128978]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Australian NHMRC [209057, 251553, 504711]; National Cancer Institute, Department of Health and Human Services, USA; Agency for Science, Technology and Research of Singapore (A*STAR); U.S. National Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation; Marit and Hans Rausings Initiative Against Breast Cancer; Yorkshire Cancer Research and the Breast Cancer Campaign; UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; Massachusetts (KME) [R01CA47305]; Wisconsin (PAN) [R01 CA47147]; New Hampshire (LT-E) [R01CA69664]; Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA FX BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme [BM0606]. DF Easton is a Principal Research Fellow of CR-UK. RL Milne is supported by Fondo de Investigacion Sanitario (PI11/00923). The Australian Breast Cancer Family Registry (ABCFR; 1992-1995) was supported by the Australian NHMRC, the New South Wales Cancer Council, and the Victorian Health Promotion Foundation (Australia). The Breast Cancer Family Registry (BCFR) was supported by the National Cancer Institute, National Institutes of Health, under RFA # CA-06-503, and through cooperative agreements with members of the BCFR and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (U01 CA69417), University of Melbourne (U01 CA69638), and Georgetown University Medical Center Informatics Support Center (HHSN261200900010C). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating BCFR centres, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. JL Hopper is an Australia Fellow and MC Southey is a Senior Research Fellow of the National Health and Medical Research Council (NHMRC) of Australia. MC Southey and JL Hopper are Group Leaders of the Victorian Breast Cancer Research Consortium. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The CECILE study was funded by the Fondation de France, the French National Institute of Cancer (INCa), The National League against Cancer, the National Agency for Environmental and Occupational Health and Food Safety (ANSES), the National Agency for Research (ANR), and the Association for Research against Cancer (ARC). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev Hospital. The CTS was supported by the California Breast Cancer Act of 1993, National Institutes of Health (grants R01 CA77398 and the Lon V Smith Foundation [LVS39420]), and the California Breast Cancer Research Fund (contract 97-10500). Collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The ESTHER study was supportd by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe).; The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114; the Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e.V. [70492] and genotyping in part by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm [P. 685]. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland, and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation; the NHMRC; the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC [145684, 288704, 454508]. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC [199600]. AB Spurdle is supported by an NHMRC Senior Research Fellowship. LMBC is supported by the "Stichting tegen Kanker" (232-2008 and 196-2010). The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I], the Hamburg Cancer Society, the German Cancer Research Center, and genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. The MCBCS was supported by the NIH grants [CA122340, CA128978] and a Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The Singapore and Swedish Breast Cancer Study (SASBAC) was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR); the U.S. National Institute of Health (NIH); the Susan G. Komen Breast Cancer Foundation; and Marit and Hans Rausings Initiative Against Breast Cancer. The SBCS was supported by Yorkshire Cancer Research and the Breast Cancer Campaign. SEARCH is funded by grants from Cancer Research UK [C490/A6187, C490/A10119, C490/A10124] and the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The US3SS study was supported by Massachusetts (KME, R01CA47305), Wisconsin (PAN, R01 CA47147), and New Hampshire (LT-E, R01CA69664) centers and by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The USRT study was funded by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 55 Z9 55 U1 5 U2 36 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2013 VL 9 IS 3 AR e1003284 DI 10.1371/journal.pgen.1003284 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 116EY UT WOS:000316866700004 PM 23544014 ER PT J AU Spielmans, GI Berman, MI Linardatos, E Rosenlicht, NZ Perry, A Tsai, AC AF Spielmans, Glen I. Berman, Margit I. Linardatos, Eftihia Rosenlicht, Nicholas Z. Perry, Angela Tsai, Alexander C. TI Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes SO PLOS MEDICINE LA English DT Article ID EXTENDED-RELEASE QUETIAPINE; TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED-TRIAL; A-DOUBLE-BLIND; CLINICAL-TRIALS; OLANZAPINE/FLUOXETINE COMBINATION; INADEQUATE-RESPONSE; RISPERIDONE AUGMENTATION AB Background: Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk-benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. Methods and Findings: We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio [OR], 2.01; 95% CI, 1.48-2.73), OFC (OR, 1.42; 95% CI, 1.01-2.0), quetiapine (OR, 1.79; 95% CI, 1.33-2.42), and risperidone (OR, 2.37; 95% CI, 1.31-4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58-2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87-1.93), quetiapine (OR, 1.53, 95% CI, 1.17-2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16-2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery-Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g = 0.49). Treatment was linked to several adverse events, including akathisia (aripiprazole), sedation (quetiapine, OFC, and aripiprazole), abnormal metabolic laboratory results (quetiapine and OFC), and weight gain (all four drugs, especially OFC). Shortcomings in study design and data reporting, as well as use of post hoc analyses, may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events. Conclusions: Atypical antipsychotic medications for the adjunctive treatment of depression are efficacious in reducing observer-rated depressive symptoms, but clinicians should interpret these findings cautiously in light of (1) the small-to-moderate-sized benefits, (2) the lack of benefit with regards to quality of life or functional impairment, and (3) the abundant evidence of potential treatment-related harm. C1 [Spielmans, Glen I.; Perry, Angela] Metropolitan State Univ, Dept Psychol, St Paul, MN USA. [Berman, Margit I.; Linardatos, Eftihia] Dartmouth Med Sch, Dept Psychiat, Lebanon, NH USA. [Rosenlicht, Nicholas Z.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Rosenlicht, Nicholas Z.] San Francisco VA Med Ctr, San Francisco, CA USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. RP Spielmans, GI (reprint author), Metropolitan State Univ, Dept Psychol, St Paul, MN USA. EM glen.spielmans@metrostate.edu OI Tsai, Alexander/0000-0001-6397-7917 FU US National Institute of Mental Health [K23 MH-096620] FX ACT acknowledges salary support through Mentored Patient-Oriented Research Career Development Award K23 MH-096620, US National Institute of Mental Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 84 TC 68 Z9 68 U1 4 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAR PY 2013 VL 10 IS 3 AR e1001403 DI 10.1371/journal.pmed.1001403 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA 115GM UT WOS:000316800600008 PM 23554581 ER PT J AU Djonovic, S Urbach, JM Drenkard, E Bush, J Feinbaum, R Ausubel, JL Traficante, D Risech, M Kocks, C Fischbach, MA Priebe, GP Ausubel, FM AF Djonovic, Slavica Urbach, Jonathan M. Drenkard, Eliana Bush, Jenifer Feinbaum, Rhonda Ausubel, Jonathan L. Traficante, David Risech, Martina Kocks, Christine Fischbach, Michael A. Priebe, Gregory P. Ausubel, Frederick M. TI Trehalose Biosynthesis Promotes Pseudomonas aeruginosa Pathogenicity in Plants SO PLOS PATHOGENS LA English DT Article ID CELL-WALL STRUCTURE; CAENORHABDITIS-ELEGANS; ARABIDOPSIS-THALIANA; BACTERIAL VIRULENCE; EXPRESSION PROFILES; MICROARRAY ANALYSIS; ESCHERICHIA-COLI; CYSTIC-FIBROSIS; INNATE IMMUNITY; OSMOTIC-STRESS AB Pseudomonas aeruginosa strain PA14 is a multi-host pathogen that infects plants, nematodes, insects, and vertebrates. Many PA14 factors are required for virulence in more than one of these hosts. Noting that plants have a fundamentally different cellular architecture from animals, we sought to identify PA14 factors that are specifically required for plant pathogenesis. We show that synthesis by PA14 of the disaccharide trehalose is required for pathogenesis in Arabidopsis, but not in nematodes, insects, or mice. In-frame deletion of two closely-linked predicted trehalose biosynthetic operons, treYZ and treS, decreased growth in Arabidopsis leaves about 50 fold. Exogenously co-inoculated trehalose, ammonium, or nitrate, but not glucose, sulfate, or phosphate suppressed the phenotype of the double Delta treYZ Delta treS mutant. Exogenous trehalose or ammonium nitrate does not suppress the growth defect of the double Delta treYZ Delta treS mutant by suppressing the plant defense response. Trehalose also does not function intracellularly in P. aeruginosa to ameliorate a variety of stresses, but most likely functions extracellularly, because wild-type PA14 rescued the in vivo growth defect of the Delta treYZ Delta treS in trans. Surprisingly, the growth defect of the double Delta treYZ Delta treS double mutant was suppressed by various Arabidopsis cell wall mutants that affect xyloglucan synthesis, including an xxt1xxt2 double mutant that completely lacks xyloglucan, even though xyloglucan mutants are not more susceptible to pathogens and respond like wild-type plants to immune elicitors. An explanation of our data is that trehalose functions to promote the acquisition of nitrogen-containing nutrients in a process that involves the xyloglucan component of the plant cell wall, thereby allowing P. aeruginosa to replicate in the intercellular spaces in a leaf. This work shows how P. aeruginosa, a multi-host opportunistic pathogen, has repurposed a highly conserved "house-keeping" anabolic pathway (trehalose biosynthesis) as a potent virulence factor that allows it to replicate in the intercellular environment of a leaf. C1 [Djonovic, Slavica; Urbach, Jonathan M.; Drenkard, Eliana; Bush, Jenifer; Feinbaum, Rhonda; Ausubel, Jonathan L.; Kocks, Christine; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Djonovic, Slavica; Drenkard, Eliana; Feinbaum, Rhonda; Kocks, Christine; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Fischbach, Michael A.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Traficante, David; Risech, Martina; Priebe, Gregory P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Priebe, Gregory P.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Div Crit Care Med, Boston, MA USA. RP Djonovic, S (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU MBRC Tosteson Fellowship; Program for Breakthrough Biomedical Research; NIH [DP2 OD007290, R01 HL092515, R37 GM48707, R01 AI085581]; NSF [MCB-0519898] FX This work was funded by an MBRC Tosteson Fellowship awarded to SD, an Opportunity Award from the Program for Breakthrough Biomedical Research and NIH grant DP2 OD007290 awarded to MAF, NIH grant R01 HL092515 awarded to GPP, and NIH grants R37 GM48707 and R01 AI085581 and by NSF grant MCB-0519898 awarded to FMA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 20 Z9 22 U1 3 U2 33 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAR PY 2013 VL 9 IS 3 AR e1003217 DI 10.1371/journal.ppat.1003217 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 117LB UT WOS:000316953800022 PM 23505373 ER PT J AU Jemielity, S Wang, JJ Chan, YK Ahmed, AA Li, WH Monahan, S Bu, X Farzan, M Freeman, GJ Umetsu, DT DeKruyff, RH Choe, H AF Jemielity, Stephanie Wang, Jinyize J. Chan, Ying Kai Ahmed, Asim A. Li, Wenhui Monahan, Sheena Bu, Xia Farzan, Michael Freeman, Gordon J. Umetsu, Dale T. DeKruyff, Rosemarie H. Choe, Hyeryun TI TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine SO PLOS PATHOGENS LA English DT Article ID FOLATE RECEPTOR-ALPHA; PH-DEPENDENT FUSION; HEPATITIS-A VIRUS; HEMORRHAGIC-FEVER ARENAVIRUSES; LAKE-VICTORIA-MARBURGVIRUS; T-CELL IMMUNOGLOBULIN; HUMAN DENDRITIC CELLS; NIEMANN-PICK C1; EBOLA-VIRUS; DENGUE VIRUS AB Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies. C1 [Jemielity, Stephanie; Wang, Jinyize J.; Ahmed, Asim A.; Choe, Hyeryun] Harvard Univ, Sch Med, Div Resp Dis, Childrens Hosp Boston, Boston, MA 02115 USA. [Chan, Ying Kai; Farzan, Michael] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, New England Primate Ctr, Boston, MA USA. [Li, Wenhui] Natl Inst Biol Sci, Beijing, Peoples R China. [Monahan, Sheena; Umetsu, Dale T.; DeKruyff, Rosemarie H.] Harvard Univ, Sch Med, Div Immunol, Childrens Hosp Boston, Boston, MA USA. [Bu, Xia; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Jemielity, S (reprint author), Harvard Univ, Sch Med, Div Resp Dis, Childrens Hosp Boston, Boston, MA 02115 USA. EM hchoe@scripps.edu OI Li, Wenhui/0000-0003-1305-7404 FU NIH [AI074879, AI057159, AI054456, AI089955]; Swiss National Science Foundation FX This project was supported by NIH grants AI074879 to HC, AI057159 to HC and MF and AI054456 and AI089955 to GJF, DTU and RHD (http://www.nih.gov). SJ was supported by a fellowship from the Swiss National Science Foundation (http://www.snf.ch/E/Pages/default.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 69 Z9 75 U1 3 U2 36 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD MAR PY 2013 VL 9 IS 3 AR e1003232 DI 10.1371/journal.ppat.1003232 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 117LB UT WOS:000316953800032 PM 23555248 ER PT J AU Buxton, D Potter, MP Bostic, JQ AF Buxton, David Potter, Mona Patel Bostic, Jeff Q. TI Coping Strategies for Child Bully-Victims SO PSYCHIATRIC ANNALS LA English DT Article ID SCHOOL-STUDENTS; PARENTAL MALTREATMENT; MIDDLE SCHOOL; VICTIMIZATION; ASSOCIATIONS; RISK; INTERVENTION; ADOLESCENCE; EXPERIENCES; DEPRESSION C1 [Buxton, David] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buxton, David] McLean Hosp, Belmont, MA USA. [Potter, Mona Patel; Bostic, Jeff Q.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Potter, Mona Patel; Bostic, Jeff Q.] Massachusetts Gen Hosp, Sch Psychiat, Dept Psychiat, Boston, MA 02114 USA. [Bostic, Jeff Q.] Massachusetts Gen Hosp, Massachusetts Child Psychiat Access Project Site, Boston, MA 02114 USA. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, Sch Psychiat, Dept Psychiat, Boston, MA 02114 USA. EM jbostic@partners.org NR 31 TC 0 Z9 0 U1 1 U2 10 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAR PY 2013 VL 43 IS 3 BP 101 EP 105 DI 10.3928/00485713-20130306-04 PG 5 WC Psychiatry SC Psychiatry GA 118CN UT WOS:000317000200004 ER PT J AU Parker, AM Liu, XG Harris, AD Shanholtz, CB Smith, RL Hess, DR Reynolds, M Netzer, G AF Parker, Ann M. Liu, Xinggang Harris, Anthony D. Shanholtz, Carl B. Smith, Robin L. Hess, Dean R. Reynolds, Marty Netzer, Giora TI Respiratory Therapy Organizational Changes Are Associated With Increased Respiratory Care Utilization SO RESPIRATORY CARE LA English DT Article DE personnel staffing and scheduling; critical care; respiratory care units; mechanical ventilators; health resources; work load ID VENTILATOR-ASSOCIATED PNEUMONIA; POSTOPERATIVE PULMONARY COMPLICATIONS; RESISTANT PSEUDOMONAS-AERUGINOSA; MECHANICAL VENTILATION; STAPHYLOCOCCUS-AUREUS; HOSPITALIZED-PATIENTS; WEANING PROTOCOL; CHEST PERCUSSION; PATIENT OUTCOMES; DRIVEN PROTOCOLS AB BACKGROUND: The effect of the respiratory therapist (RT)/patient ratio and RT organizational factors on respiratory resource utilization is unknown. We describe the impact of a multi-component intervention that called for an increase in RT/patient ratio (1:14 to 1:10), improved RT orientation, and formation of a core staffing model on best practice, including spontaneous breathing trials (SSTs) and catheter and bronchoscopically directed lower respiratory tract cultures, or bronchoalveolar lavage (BAL), in both ventilated and non-ventilated patients in the ICU. METHODS: We conducted a single center, quasi-experimental study comparing 651 patients with single and first admissions between April 19, 2005 and April 18, 2006 before the RT services reorganization with 1,073 patients with single and first admissions between September 16, 2007 and September 4, 2008. Baseline characteristics were compared, along with SBTs, BAL use, lower respiratory tract cultures, and chest physiotherapy. RESULTS: Patients in the 2 groups were similar in terms of age (52.9 +/- 15.8 y vs 53.9 +/- 16.4 y, P = .23), comorbidity as measured by Charlson score (2.8 +/- 2.6 vs 2.8 +/- 2.7, P = .56), and acuity of illness as measured by the Case Mix Index (3.2 +/- 3.9 vs 3.3 +/- 4.1, P = .47). Mechanically ventilated patients had similar prevalences of respiratory diseases (24.2% vs 25.1%, P = .61). There was an increase in SBTs (0.5% vs 73.1%, P < .001), chest physiotherapy (7.4% vs 21.6%, P < .001), BALs (24.0% vs 41.4%, P < .001), and lower respiratory tract cultures (21.5% vs 38.0%, P < .001) in mechanically ventilated patients post-intervention. CONCLUSIONS: A multi-component intervention, including an increase in RT/patient ratio, improved RT orientation, and establishment of a core staffing model, was associated with increased respiratory resource utilization and evidence-based practice, specifically BALs and SBTs. C1 [Parker, Ann M.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Liu, Xinggang; Harris, Anthony D.; Netzer, Giora] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Shanholtz, Carl B.; Netzer, Giora] Univ Maryland, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. [Smith, Robin L.; Reynolds, Marty] Univ Maryland, Med Ctr, Dept Resp Care, Baltimore, MD 21201 USA. [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA USA. [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Parker, AM (reprint author), Johns Hopkins Univ, Div Pulm & Crit Care Med, 1830 E Monument St, Baltimore, MD 21205 USA. EM aparke36@jhu.edu OI Shanholtz, Carl/0000-0003-3938-178X FU National Institutes of Health FX Editor in Chief Dean Hess was blinded to the peer review of this paper, which was managed by Deputy Editor Richard Branson. Dr Netzer was supported by a National Institutes of Health Clinical Research Career Development Award. Dr Harris was supported by a National Institutes of Health Midcareer Investigator Grant. NR 47 TC 2 Z9 2 U1 0 U2 5 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 MAR PY 2013 VL 58 IS 3 BP 438 EP 449 DI 10.4187/respcare.01562 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 110IB UT WOS:000316434700004 PM 22782139 ER PT J AU Mechanick, JI Youdim, A Jones, DB Garvey, WT Hurley, DL McMahon, MM Heinberg, LJ Kushner, R Adams, TD Shikora, S Dixon, JB Brethauer, S AF Mechanick, Jeffrey I. Youdim, Adrienne Jones, Daniel B. Garvey, W. Timothy Hurley, Daniel L. McMahon, M. Molly Heinberg, Leslie J. Kushner, Robert Adams, Ted D. Shikora, Scott Dixon, John B. Brethauer, Stacy TI Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient-2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Bariatric surgery; Obesity; Metabolic surgery; Diabetes surgery; Metabolic syndrome; Clinical practice guidelines; Best practice guidelines; Weight loss surgery ID Y-GASTRIC-BYPASS; LAPAROSCOPIC-SLEEVE-GASTRECTOMY; TYPE-2 DIABETES-MELLITUS; WEIGHT-LOSS SURGERY; PROSPECTIVE-RANDOMIZED-TRIAL; OF-THE-LITERATURE; BODY-MASS INDEX; OUTCOMES LONGITUDINAL DATABASE; HELICOBACTER-PYLORI INFECTION; CARDIOVASCULAR RISK-FACTORS AB The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE-TOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues. (Surg Obes Relat Dis 2013;9:159-191.) (C) 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved. C1 [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, New York, NY 10128 USA. [Youdim, Adrienne] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Jones, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, AACE, Birmingham VA Med Ctr, Birmingham, AL USA. [Hurley, Daniel L.; McMahon, M. Molly] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, AACE, Rochester, MN USA. [Heinberg, Leslie J.] Cleveland Clin, Lerner Coll Med, TOS, BMI Director Behav Serv, Cleveland, OH 44106 USA. [Kushner, Robert] Northwestern Univ, TOS, Feinberg Sch Med, Chicago, IL 60611 USA. [Adams, Ted D.] Univ Utah, Sch Med, Hlth & Fitness Inst, TOS,Intermt Healthcare & Cardiovasc Genet Div, Salt Lake City, UT USA. [Shikora, Scott] Harvard Univ, Brigham & Womens Hosp, ASMBS, Med Sch,Ctr Metab Hlth & Bariatr Surg, Boston, MA 02115 USA. [Dixon, John B.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Brethauer, Stacy] Cleveland Clin, Lerner Coll Med, Bariatr & Metab Inst, ASMBS, Cleveland, OH 44106 USA. RP Mechanick, JI (reprint author), Icahn Sch Med Mt Sinai, 1192 Pk Ave, New York, NY 10128 USA. EM jeffreymechanick@gmail.com NR 395 TC 142 Z9 151 U1 2 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAR-APR PY 2013 VL 9 IS 2 BP 159 EP 191 DI 10.1016/j.soard.2012.12.010 PG 33 WC Surgery SC Surgery GA 117BA UT WOS:000316925900001 PM 23537696 ER PT J AU Udayasankar, J Zraika, S Aston-Mourney, K Subramanian, SL Brooks-Worrell, BM Taborsky, GJ Hull, RL AF Udayasankar, J. Zraika, S. Aston-Mourney, K. Subramanian, S. L. Brooks-Worrell, B. M. Taborsky, G. J. Hull, R. L. TI Rosiglitazone Treatment Does Not Decrease Amyloid Deposition in Transplanted Islets From Transgenic Mice Expressing Human Islet Amyloid Polypeptide SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID DIABETES-MELLITUS; MOUSE ISLETS; HYPERGLYCEMIA; DYSFUNCTION; ACTIVATION; PREVENTS; LANGERHANS; SECRETION; METFORMIN; PANCREAS AB In human islet transplantation, insulin independence decreases over time. We previously showed that amyloid deposition following transplantation of islets from human islet amyloid polypeptide (hIAPP) transgenic mice resulted in B-cell loss and that rosiglitazone treatment decreased islet amyloid deposition and preserved B-cell area in the endogenous pancreas of hIAPP transgenic mice. Thus, we sought to determine if rosiglitazone treatment decreases islet amyloid deposition and the associated B-cell loss after islet transplantation. Streptozocin-diabetic mice were transplanted with 100 islets from hIAPP transgenic (T) mice or nontransgenic (NT) littermates under the kidney capsule and received either rosiglitazone (R) in drinking water or plain drinking water (C). The resultant groups (NTC [n = 11], NTR [n = 9], TC [n = 14], and TR [n = 10]) were followed for 12 weeks after which the graft was removed and processed for histology. Amyloid was detected in nearly all T islet grafts (TC = 13/14, TR = 10/10) but not in NT grafts. Rosiglitazone did not alter amyloid deposition (% graft area occupied by amyloid; TC: 2.15 +/- 0.7, TR: 1.72 +/- 0.66; P = .86). % beta-celligraft area was decreased in the TC grafts compared to NTC (56.2 +/- 3.1 vs 73.8 +/- 1.4; P < .0001) but was not different between TC and TR groups (56.2 +/- 3.1 vs 61.0 +/- 2.9; P = .34). Plasma glucose levels before and after transplantation did not differ between NTC and TC groups and rosiglitazone did not affect plasma glucose levels post islet transplantation. Rosiglitazone did not decrease amyloid deposition in hIAPP transgenic islet grafts. Therefore, rosiglitazone treatment of recipients of amyloid forming islets may not improve transplantation outcomes. C1 VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@u.washington.edu OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Hull, Rebecca/0000-0001-9690-4087 FU Department of Veterans Affairs; VA Puget Sound Health Care System (Seattle, WA, USA); GlaxoSmithKline [DK74404, DK80945, DK017047]; Juvenile Diabetes Research Foundation Postdoctoral Fellowship; American Diabetes Association Mentor-Based Fellowship; University of Washington McAbee Fellowship; NIH [DK007247] FX This work was supported by the Department of Veterans Affairs, VA Puget Sound Health Care System (Seattle, WA, USA), an investigator-initiated research grant from GlaxoSmithKline (GJT), DK74404 (RLH), DK80945 (SZ), DK017047 (University of Washington Diabetes Research Center, Cellular and Molecular Imaging Core), Juvenile Diabetes Research Foundation Postdoctoral Fellowship (JU), American Diabetes Association Mentor-Based Fellowship (KAM), University of Washington McAbee Fellowship (KAM) and NIH-training grant DK007247 (SLS). NR 37 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD MAR PY 2013 VL 45 IS 2 BP 574 EP 579 DI 10.1016/j.transproceed.2012.05.079 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 114WA UT WOS:000316772500019 PM 23267797 ER PT J AU Badell, IR Hanish, SI Hughes, CB Hewitt, WR Chung, RT Spivey, JR Knechtle, SJ AF Badell, I. R. Hanish, S. I. Hughes, C. B. Hewitt, W. R. Chung, R. T. Spivey, J. R. Knechtle, S. J. TI Domino Liver Transplantation in Maple Syrup Urine Disease: A Case Report and Review of the Literature SO TRANSPLANTATION PROCEEDINGS LA English DT Review ID CHILDREN; ADULTS AB Background. Improved outcomes have expanded the indications for liver transplantation, thus aggravating the already limited supply of donor organs. Domino liver transplantation (DLT) has been one strategy to augment the supply of donor organs in cases of inborn errors of metabolism. One such disease is maple syrup urine disease (MSUD), an inherited disorder of branched-chain amino acid (BCAA) metabolism. Methods. We report on the transplantation of a deceased donor liver into a patient with MSUD, and the sequential transplantation of the explanted liver into a patient with hemophilia A, HIV, hepatitis C, and a low priority on the transplant waiting list. Results. At 30 months, the MSUD recipient has had significant correction of BCAA metabolism on a protein-unrestricted diet and no progression of neuropsychiatric symptoms. The DLT recipient has been cured of hemophilia and has normal BCAA homeostasis. This case provides further evidence that elective orthotopic liver transplantation for MSUD attenuates the disease with restoration of BCAA metabolism, and that DLT in this setting can achieve excellent results in ESLD patients. Conclusion. It is possible that domino grafts from patients with MSUD could be used in more conventional recipients, but additional studies and longer-term outcomes are needed to determine the validity of DLT in MSUD. C1 [Badell, I. R.; Hanish, S. I.; Hughes, C. B.; Hewitt, W. R.; Spivey, J. R.; Knechtle, S. J.] Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA. [Chung, R. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Knechtle, SJ (reprint author), Emory Transplant Ctr, Div Transplant Surg, Dept Surg, 101 Woodruff Circle,WMB 5105, Atlanta, GA 30322 USA. EM Stuart.Knechtle@emoryhealthcare.org NR 19 TC 7 Z9 7 U1 1 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD MAR PY 2013 VL 45 IS 2 BP 806 EP 809 DI 10.1016/j.transproceed.2012.04.031 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 114WA UT WOS:000316772500060 PM 23267808 ER PT J AU Hari, R Himberg, T Nummenmaa, L Hamalainen, M Parkkonen, L AF Hari, Riitta Himberg, Tommi Nummenmaa, Lauri Hamalainen, Matti Parkkonen, Lauri TI Synchrony of brains and bodies during implicit interpersonal interaction SO TRENDS IN COGNITIVE SCIENCES LA English DT Editorial Material ID SOCIAL-INTERACTION; MOTION AB To successfully interact with others, people automatically mimic their actions and feelings. Yet, neurobehavioral studies of interaction are few because of lacking conceptual and experimental frameworks. A recent study introduced an elegantly simple motor task to unravel implicit interpersonal behavioral synchrony and brain function during face-to-face interaction. C1 [Hari, Riitta; Himberg, Tommi; Hamalainen, Matti] Aalto Univ, Brain Res Unit, OV Lounasmaa Lab, Espoo, Finland. [Nummenmaa, Lauri; Parkkonen, Lauri] Aalto Univ, Dept Biomed Engn & Computat Sci, Espoo, Finland. [Nummenmaa, Lauri] Turku Univ Hosp, Turku PET Ctr, FIN-20520 Turku, Finland. [Hamalainen, Matti] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Hari, R (reprint author), Aalto Univ, Brain Res Unit, OV Lounasmaa Lab, Espoo, Finland. EM riitta.hari@aalto.fi RI Hari, Riitta/J-1880-2012; Hamalainen, Matti/C-8507-2013; Nummenmaa, Lauri/G-6910-2012; Parkkonen, Lauri/G-6755-2012 OI Hari, Riitta/0000-0002-3142-2703; Nummenmaa, Lauri/0000-0002-2497-9757; Parkkonen, Lauri/0000-0002-0130-0801 NR 10 TC 22 Z9 22 U1 2 U2 38 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD MAR PY 2013 VL 17 IS 3 BP 105 EP 106 DI 10.1016/j.tics.2013.01.003 PG 2 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 113ZT UT WOS:000316709900003 PM 23384658 ER PT J AU Gomez, DI Twahirwa, M Schlesinger, LS Restrepo, BI AF Gomez, Diana I. Twahirwa, Marcel Schlesinger, Larry S. Restrepo, Blanca I. TI Reduced Mycobacterium tuberculosis association with monocytes from diabetes patients that have poor glucose control SO TUBERCULOSIS LA English DT Article DE Tuberculosis; Diabetes; Complement; Monocyte; Mycobacterium ID MONONUCLEAR PHAGOCYTES; COMPLEMENT RECEPTORS; MELLITUS; INTERLEUKIN-12; EXPRESSION; ANTIBODIES; INCREASES; METFORMIN; RESPONSES; VIRULENT AB The re-emerging importance of type 2 diabetes mellitus (DM) to tuberculosis (TB) control is of growing concern, but the basis for this relationship is poorly understood. Given the importance of mononuclear phagocytes for TB control and the reported alterations in monocytes of DM patients, we evaluated whether the initial interaction between both was affected in diabetics. Mycobacterium tuberculosis-naive individuals with and without DM were group matched by age and gender and the efficiency of M. tuberculosis association (attachment and ingestion) with their monocytes was assessed in the presence of autologous serum. The association of M. tuberculosis with monocytes was significantly lower in diabetics (19.2 +/- 6.1) than non-diabetics (27.5 +/- 7.9; p = 0.02). Multivariate analysis controlling for host socio demographics, DM characteristics and serum lipids indicated that male gender (p = 0.04) and poorly-controlled DM (high HbA(1c) and hyperglycemia; p = 0.01) were significantly associated with the lower interaction of M. tuberculosis with monocytes. Serum heat-inactivation reduced the association of M. tuberculosis to similar levels in both study groups (p = 0.69) suggesting alterations in the complement pathway of DM patients. These findings suggest an altered route of entry of the pathogen in DM patients that may influence the downstream activation of signaling pathways in the monocyte and the survival of mycobacteria. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Gomez, Diana I.; Restrepo, Blanca I.] Univ Texas Hlth Sci Ctr San Antonio, Sch Publ Hlth Brownsville, Div Epidemiol, Brownsville, TX 78520 USA. [Twahirwa, Marcel] Doctors Hosp Renaissance, Joslin Diabet Ctr, Edinburg, TX USA. [Schlesinger, Larry S.] Ohio State Univ, Ctr Microbial Interface Biol, Columbus, OH 43210 USA. [Schlesinger, Larry S.] Ohio State Univ, Dept Microbial Infect & Immun, Columbus, OH 43210 USA. RP Restrepo, BI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Publ Hlth Brownsville, Div Epidemiol, 80 Ft Brown,SPH Bldg, Brownsville, TX 78520 USA. EM Diana.i.gomez@gmail.com; m.twahirwa@dhr-rgv.com; larry.schlesinger@osumc.edu; blanca.i.restrepo@uth.tmc.edu FU National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R21AI079624-01A1] FX This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant number R21AI079624-01A1). The sponsor had no role in the study design, collection, analysis or interpretation of data. NR 39 TC 26 Z9 27 U1 0 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD MAR PY 2013 VL 93 IS 2 BP 192 EP 197 DI 10.1016/j.tube.2012.10.003 PG 6 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 114IJ UT WOS:000316734000011 PM 23131496 ER PT J AU Bhargava, P Lackey, AE Dhand, S Moshiri, M Jambhekar, K Pandey, T AF Bhargava, Puneet Lackey, Amanda E. Dhand, Sabeen Moshiri, Mariam Jambhekar, Kedar Pandey, Tarun TI Radiology Education 2.0-On the Cusp of Change: Part 1. Tablet Computers, Online Curriculums, Remote Meeting Tools and Audience Response Systems SO ACADEMIC RADIOLOGY LA English DT Article DE Radiology education; tablet computers; portable devices ID RESOURCES; RETENTION; INTERNET; FUTURE AB We are in the midst of an evolving educational revolution. Use of digital devices such as smart phones and tablet computers is rapidly increasing among radiologists who now regularly use them for medical, technical, and administrative tasks. These electronic tools provide a wide array of new tools to the radiologists allowing for faster, more simplified, and widespread distribution of educational material. The utility, future potential, and limitations of some these powerful tools are discussed in this article. C1 [Bhargava, Puneet] Univ Washington, Dept Radiol, Seattle, WA 98108 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Lackey, Amanda E.; Jambhekar, Kedar; Pandey, Tarun] Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA. [Dhand, Sabeen] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Moshiri, Mariam] Univ Washington, Med Ctr, Seattle, WA 98108 USA. RP Bhargava, P (reprint author), Univ Washington, Dept Radiol, Mail Box 358280,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 21 TC 14 Z9 14 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2013 VL 20 IS 3 BP 364 EP 372 DI 10.1016/j.acra.2012.11.002 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109LE UT WOS:000316369200015 PM 23452483 ER PT J AU Bhargava, P Dhand, S Lackey, AE Pandey, T Moshiri, M Jambhekar, K AF Bhargava, Puneet Dhand, Sabeen Lackey, Amanda E. Pandey, Tarun Moshiri, Mariam Jambhekar, Kedar TI Radiology Education 2.0-On the Cusp of Change: Part 2. eBooks; File Sharing and Synchronization Tools; Websites/Teaching Files; Reference Management Tools and Note Taking Applications SO ACADEMIC RADIOLOGY LA English DT Article ID INTERNET AB Increasing use of smartphones and handheld computers is accompanied by a rapid growth in the other related industries. Electronic books have revolutionized the centuries-old conventional books and magazines markets and have simplified publishing by reducing the cost and processing time required to create and distribute any given book. We are now able to read, review, store, and share various types of documents via several electronic tools, many of which are available free of charge. Additionally, this electronic revolution has resulted in an explosion of readily available Internet-based educational resources for the residents and has paved the path for educators to reach out to a larger and more diverse student population. (C)AUR, 2013 C1 [Bhargava, Puneet] Univ Washington, Dept Radiol, Seattle, WA 98108 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Dhand, Sabeen] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Moshiri, Mariam] Univ Washington, Med Ctr, Seattle, WA 98108 USA. [Lackey, Amanda E.; Pandey, Tarun; Jambhekar, Kedar] Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA. RP Bhargava, P (reprint author), Univ Washington, Dept Radiol, Mail Box 358280,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 8 TC 13 Z9 13 U1 1 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2013 VL 20 IS 3 BP 373 EP 381 DI 10.1016/j.acra.2012.11.001 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109LE UT WOS:000316369200016 PM 23452484 ER PT J AU Haussen, DC Henninger, N Selim, M AF Haussen, Diogo C. Henninger, Nils Selim, Magdy TI Diffusion-weighted imaging of intramural hematoma in internal carotid artery dissection SO ACTA NEUROLOGICA BELGICA LA English DT Editorial Material ID CEREBRAL VENOUS THROMBOSIS C1 [Haussen, Diogo C.; Henninger, Nils; Selim, Magdy] Harvard Univ, Sch Med, Beth Israel Deacones Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Haussen, DC (reprint author), Harvard Univ, Sch Med, Beth Israel Deacones Med Ctr, Dept Neurol, 330 Brookline Ave,Palmer 127,West Campus, Boston, MA 02215 USA. EM dhaussen@gmail.com OI Henninger, Nils/0000-0002-3883-5623 NR 4 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-9009 J9 ACTA NEUROL BELG JI Acta Neurol. Belg. PD MAR PY 2013 VL 113 IS 1 BP 109 EP 110 DI 10.1007/s13760-012-0131-0 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 107OF UT WOS:000316226800026 PM 22975838 ER PT J AU Potter, CM Kaiser, AP King, LA King, DW Davison, EH Seligowski, AV Brady, CB Spiro, A AF Potter, Carrie M. Kaiser, Anica Pless King, Lynda A. King, Daniel W. Davison, Eve H. Seligowski, Antonia V. Brady, Christopher B. Spiro, Avron, III TI Distinguishing late-onset stress symptomatology from posttraumatic stress disorder in older combat veterans SO AGING & MENTAL HEALTH LA English DT Article DE aging male combat veterans; war experiences; re-engagement; discriminant validity ID MILITARY SERVICE; LIFE; SATISFACTION; SCALE AB Objective: To assess the discriminant validity of late-onset stress symptomatology (LOSS) in terms of its distinction from posttraumatic stress disorder (PTSD). Method: The LOSS Scale, PTSD Checklist Civilian Version, and related psychological measures were administered to 562 older male combat veterans via a mailed questionnaire. Analyses focused on: (a) comparing associations of LOSS and PTSD with other psychological variables and (b) examining a hypothesized curvilinear relationship between LOSS and PTSD scores. Results: Compared to PTSD, LOSS was more strongly associated with concerns about retirement and less strongly associated with depression, anxiety, sense of mastery, and satisfaction with life. LOSS also demonstrated a curvilinear relationship with PTSD, such that the positive association between LOSS and PTSD diminished at higher levels of PTSD. Conclusion: LOSS is conceptually and statistically more strongly associated with a normative late-life stressor than is PTSD, but is less strongly related to mental health symptoms and emotional well-being. Additionally, LOSS seems more related to subthreshold PTSD than it is to clinically significant PTSD. The present findings support the discriminant validity of LOSS. C1 [Potter, Carrie M.; Kaiser, Anica Pless; King, Lynda A.; King, Daniel W.; Seligowski, Antonia V.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. [Potter, Carrie M.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Kaiser, Anica Pless; Brady, Christopher B.; Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Kaiser, Anica Pless; King, Lynda A.; King, Daniel W.; Davison, Eve H.; Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Davison, Eve H.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Brady, Christopher B.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Brady, Christopher B.] Boston Univ, Sch Med, Program Behav Neurosci, Boston, MA 02118 USA. [Brady, Christopher B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Potter, CM (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. EM carrie.potter@temple.edu OI Brady, Christopher/0000-0002-6095-6480; Spiro III, Avron/0000-0003-4080-8621 FU US Department of Veterans Affairs; R.E. Mitchell Center for Prisoner of War Studies, Pensacola, FL; Cooperative Studies Program/Epidemiology Research and Information Centers, US Department of Veterans Affairs; Health Services Research and Development Service, US Department of Veterans Affairs [SDR 91006-S]; National Institute on Aging [R01-AG18436]; National Center for PTSD; Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System FX The views expressed in this article are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. This research was supported by funding from the US Department of Veterans Affairs, the R.E. Mitchell Center for Prisoner of War Studies, Pensacola, FL, and by a Research Career Science and Merit Review award from the US. Department of Veterans Affairs. The Normative Aging Study (NAS) and the Veterans Health Study (VHS) graciously provided access to samples of their veteran participants. The NAS is supported by the Cooperative Studies Program/Epidemiology Research and Information Centers, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center. The VHS was supported by grant SDR 91006-S from the Health Services Research and Development Service, US Department of Veterans Affairs. Additional support was provided by grant R01-AG18436 (Dan Mroczek, Principal Investigator) from the National Institute on Aging. The authors express their appreciation to colleagues of the Stress, Health, and Aging Research Program (SHARP), VA Boston Healthcare System; SHARP is supported by the National Center for PTSD and the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System. NR 24 TC 2 Z9 2 U1 1 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD MAR 1 PY 2013 VL 17 IS 2 BP 173 EP 179 DI 10.1080/13607863.2012.717259 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 100ED UT WOS:000315677700005 PM 22962937 ER PT J AU Baker, JW Craig, TJ Riedl, MA Banerji, A Fitts, D Kalfus, IN Uknis, ME AF Baker, James W. Craig, Timothy J. Riedl, Marc A. Banerji, Aleena Fitts, David Kalfus, Ira N. Uknis, Marc E. TI Nanofiltered C1 esterase inhibitor (human) for hereditary angioedema attacks in pregnant women SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID CLINICAL SYNDROME; MANAGEMENT; CONCENTRATE; PROPHYLAXIS; DIAGNOSIS; DANAZOL; EDEMA AB Data are limited on hereditary angioedema (HAE) in pregnant women and the safety and efficacy of therapies for treatment and prevention of HAE attacks during pregnancy. Prospective studies are unlikely given the rarity of HAE and ethical considerations regarding enrollment of pregnant female subjects in clinical trials. A retrospective analysis of clinical trial and compassionate-use data was conducted to identify subjects who received nanofiltered Cl esterase inhibitor (C1 INH-nf; human) during pregnancy. This study evaluates the efficacy and safety of human C1 INH-nf for treatment and prevention of HAE attacks in pregnant women. Data from pregnant subjects enrolled in either open-label extensions of two randomized, double-blind, placebo-controlled trials of C1 INH-nf or in a compassionate-use program were retrospectively analyzed for efficacy (e.g., total attacks, attack frequency during prophylaxis, and monthly attack rates) and safety (e.g., pregnancy outcomes and adverse events). C1 INH-nf was administered as acute treatment, preprocedural prophylaxis, or routine prophylaxis. C1 INH-nf prophylaxis substantially reduced monthly attack rates. Of 16 subjects, 13 delivered 14 healthy neonates (1 set of twins). Two adverse fetal outcomes were reported; neither was considered by the principal investigator to be related to C1 INH-nf. One subject's pregnancy outcome was unknown. This analysis shows a favorable risk-benefit profile for C1 INH-nf for managing HAE during pregnancy. NCT Identifi er: NCT00438815; NCT00462709.. (Allergy Asthma Proc 34:162-169, 2013; doi: 10.2500/aap.2013.34.3645) C1 [Baker, James W.] Baker Allergy Asthma & Dermatol, Lake Oswego, OR 97035 USA. [Craig, Timothy J.] Penn State Univ, Coll Med, Hershey, PA USA. [Riedl, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Clin Immunol & Allergy, Los Angeles, CA 90095 USA. [Banerji, Aleena] Massachusetts Gen Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02114 USA. [Fitts, David; Uknis, Marc E.] Viro Pharma Inc, Exton, PA USA. [Kalfus, Ira N.] M2G Consulting, New York, NY USA. RP Baker, JW (reprint author), Baker Allergy Asthma & Dermatol, 3975 Mercantile Dr,Suite 158, Lake Oswego, OR 97035 USA. EM jameswbaker@aadrc.com FU ViroPharma; Pharming; Shire; Dyax; CSL Behring; ViroPharma, Inc FX Editorial assistance was funded by ViroPharma, Inc; JW Baker is a speaker and receives grants from ViroPharma, Pharming and Shire. TJ Craig is a speaker, consults, or receives grants from Dyax, ViroPharma, Shire and Pharming. M Riedl is a speaker, consults or receives grants from Dyax, ViroPharma, CSL Behring, Pharming, also consults for Biocryst. A Banerji consults and receives grants from Shire, Dyax and CSL Behring. D Fitts is an employee of ViroPharma. IN Kalfus is a consultant for ViroPharma. ME Uknis is a stockholder and employee for ViroPharma NR 35 TC 6 Z9 6 U1 2 U2 4 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 2013 VL 34 IS 2 BP 162 EP 169 DI 10.2500/aap.2013.34.3645 PG 8 WC Allergy SC Allergy GA 107SE UT WOS:000316240300008 PM 23484892 ER PT J AU Foley, JM Gooding, AL Thames, AD Ettenhofer, ML Kim, MS Castellon, SA Marcotte, TD Sadek, JR Heaton, RK van Gorp, WG Hinkin, CH AF Foley, J. M. Gooding, A. L. Thames, A. D. Ettenhofer, M. L. Kim, M. S. Castellon, S. A. Marcotte, T. D. Sadek, J. R. Heaton, R. K. van Gorp, W. G. Hinkin, C. H. TI Visuospatial and Attentional Abilities Predict Driving Simulator Performance Among Older HIV-infected Adults SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE HIV; aging; driving performance; independent functioning; cognition ID HUMAN-IMMUNODEFICIENCY-VIRUS; PARKINSONS-DISEASE; VISUAL-ATTENTION; MEDICATION ADHERENCE; ALZHEIMER-DISEASE; NEUROPSYCHOLOGICAL IMPAIRMENT; HUNTINGTONS-DISEASE; VEHICLE CRASHES; BASAL GANGLIA; AIDS PATIENTS AB Objectives: To examine the effects of aging and neuropsychological (NP) impairment on driving simulator performance within a human immunodeficiency virus (HIV)-infected cohort. Methods: Participants included 79 HIV-infected adults (n = 58 > age 50, n = 21 <= 40) who completed a NP battery and a personnel computer-based driving simulator task. Outcome variables included total completion time (time) and number of city blocks to complete the task (blocks). Results: Compared to the younger group, the older group was less efficient in their route finding (blocks over optimum: 25.9 [20.1] vs 14.4 [16.9]; P = .02) and took longer to complete the task (time: 1297.6 [577.6] vs 804.4 [458.5] seconds; P = .001). Regression models within the older adult group indicated that visuospatial abilities (blocks: b = -0.40, P < .001; time: b = -0.40, P = .001) and attention (blocks: b = -0.49, P = .001; time: b = -0.42, P = .006) independently predicted simulator performance. The NP-impaired group performed more poorly on both time and blocks, compared to the NP normal group. Conclusions: Older HIV-infected adults may be at risk of driving-related functional compromise secondary to HIV-associated neurocognitive decline. C1 [Foley, J. M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Foley, J. M.; Kim, M. S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Gooding, A. L.] Fordham Univ, Dept Psychol, New York, NY 10023 USA. [Thames, A. D.; Castellon, S. A.; Hinkin, C. H.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Ettenhofer, M. L.] Uniformed Serv Univ Hlth Sci, Bethesda, NE USA. [Kim, M. S.] Cambridge Hlth Alliance, Cambridge, MA USA. [Castellon, S. A.; Hinkin, C. H.] VA Med Ctr, Los Angeles, CA USA. [Marcotte, T. D.; Heaton, R. K.] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Sadek, J. R.] Univ New Mexico, New Mexico VAMC, Dept Psychiat, Albuquerque, NM 87131 USA. [van Gorp, W. G.] Columbia Presbyterian Med Ctr, New York, NY 10032 USA. RP Foley, JM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM jessicafoley@gmail.com RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189 FU VA Merit Review: Aging & HIV/AIDS: Neurocognitive Sequelae and Functional Consequences [NCT00675766] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: VA Merit Review: Aging & HIV/AIDS: Neurocognitive Sequelae and Functional Consequences to CHH [grant number NCT00675766]. NR 75 TC 10 Z9 10 U1 6 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD MAR PY 2013 VL 28 IS 2 BP 185 EP 194 DI 10.1177/1533317512473192 PG 10 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA 112YB UT WOS:000316630100012 PM 23314403 ER PT J AU Friedrichsen, M Birk, JB Richter, EA Ribel-Madsen, R Pehmoller, C Hansen, BF Beck-Nielsen, H Hirshman, MF Goodyear, LJ Vaag, A Poulsen, P Wojtaszewski, JFP AF Friedrichsen, Martin Birk, Jesper B. Richter, Erik A. Ribel-Madsen, Rasmus Pehmoller, Christian Hansen, Bo Falck Beck-Nielsen, Henning Hirshman, Michael F. Goodyear, Laurie J. Vaag, Allan Poulsen, Pernille Wojtaszewski, Jorgen F. P. TI Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH2-terminal (sites 2+2a) phosphorylation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glycogen synthesis; insulin signaling; muscle; phosphatidylinositol 3-kinase/protein kinase B; diabetes ID DEPENDENT DIABETES-MELLITUS; PROTEIN-KINASE-B; INSULIN ACTION; GLUCOSE-TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE; LIPID-METABOLISM; ACTIVATION; EXERCISE; TWINS; SENSITIVITY AB Friedrichsen M, Birk JB, Richter EA, Ribel-Madsen R, Pehmoller C, Hansen BF, Beck-Nielsen H, Hirshman MF, Goodyear LJ, Vaag A, Poulsen P, Wojtaszewski JF. Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH2-terminal (sites 2 + 2a) phosphorylation. Am J Physiol Endocrinol Metab 67: E631-E639, 2013. First published January 15, 2012; doi:10.1152/ajpendo.00494.2012.-Type 2 diabetes is characterized by reduced muscle glycogen synthesis. The key enzyme in this process, glycogen synthase (GS), is activated via proximal insulin signaling, but the exact molecular events remain unknown. Previously, we demonstrated that phosphorylation of Thr(308) on Akt (p-Akt-Thr(308)), Akt2 activity, and GS activity in muscle were positively associated with insulin sensitivity. Here, in the same study population, we determined the influence of several upstream elements in the canonical PI3K signaling on muscle GS activation. One-hundred eighty-one nondiabetic twins were examined with the euglycemic hyperinsulinemic clamp combined with excision of muscle biopsies. Insulin signaling was evaluated at the levels of the insulin receptor, IRS-1-associated PI3K (IRS-1-PI3K), Akt, and GS employing activity assays and phosphospecific Western blotting. The insulin-stimulated GS activity was positively associated with p-Akt-Thr(308) (P = 0.01) and Akt2 activity (P = 0.04) but not p-Akt-Ser(473) or IRS-1-PI3K activity. Furthermore, p-Akt-Thr(308) and Akt2 activity were negatively associated with NH2-terminal GS phosphorylation (P = 0.001 for both), which in turn was negatively associated with insulin-stimulated GS activity (P < 0.001). We found no association between COOH-terminal GS phosphorylation and Akt or GS activity. Employing whole body Akt2-knockout mice, we validated the necessity for Akt2 in insulin-mediated GS activation. However, since insulin did not affect NH2-terminal phosphorylation in mice, we could not use this model to validate the observed association between GS NH2-terminal phosphorylation and Akt activity in humans. In conclusion, our study suggests that although COOH-terminal dephosphorylation is likely necessary for GS activation, Akt2-dependent NH2-terminal dephosphorylation may be the site for "fine-tuning" insulin-mediated GS activation in humans. C1 [Friedrichsen, Martin; Ribel-Madsen, Rasmus; Vaag, Allan; Poulsen, Pernille] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Friedrichsen, Martin] Univ Copenhagen, Dept Biomed Sci, DK-2100 Copenhagen, Denmark. [Friedrichsen, Martin; Birk, Jesper B.; Richter, Erik A.; Pehmoller, Christian; Wojtaszewski, Jorgen F. P.] Univ Copenhagen, Mol Physiol Grp, August Krogh Ctr, Dept Nutr Exercise & Sports, DK-2100 Copenhagen, Denmark. [Pehmoller, Christian; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, Boston, MA 02115 USA. [Hansen, Bo Falck; Poulsen, Pernille] Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. [Beck-Nielsen, Henning] Odense Univ Hosp, Diabet Res Ctr, DK-5000 Odense, Denmark. [Vaag, Allan] Rigshosp, Dept Diabet & Metab, DK-2100 Copenhagen, Denmark. RP Friedrichsen, M (reprint author), Univ Copenhagen, Mol Physiol Grp, August Krogh Ctr, Dept Nutr Exercise & Sports, DK-2100 Copenhagen, Denmark. EM martin.friedrichsen@ifi.ku.dk RI Wojtaszewski, Jorgen /P-6583-2014; Friedrichsen, Martin/A-3638-2015; Birk, Jesper/D-3523-2015 OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Friedrichsen, Martin/0000-0003-3383-9593; Birk, Jesper/0000-0001-9775-4789 FU Danish Agency for Science Technology and Innovation; Danish Medical Research Council; Danish Strategic Research Council; Novo Nordisk Foundation; Danish Diabetes Association; Lundbeck Foundation; UNIK Project: Food, Fitness, & Pharma for Health and Disease; Danish Ministry of Science, Technology, and Innovation; integrated 6th Frame Work EU project (EXGENESIS) from the European Union [LSHM-CT-2004-005272]; National Institutes of Health [R01-AR-42238] FX M. Friedrichsen was supported by a grant from the Danish Agency for Science Technology and Innovation. This study was supported by grants from the Danish Medical Research Council, the Danish Strategic Research Council, the Novo Nordisk Foundation, the Danish Diabetes Association, the Lundbeck Foundation, The UNIK Project: Food, Fitness, & Pharma for Health and Disease, supported by the Danish Ministry of Science, Technology, and Innovation, and an integrated 6th Frame Work EU project (EXGENESIS) (contract no. LSHM-CT-2004-005272) from the European Union. This work was supported in part by the National Institutes of Health (R01-AR-42238 to L. J. Goodyear). NR 45 TC 5 Z9 5 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2013 VL 304 IS 6 BP E631 EP E639 DI 10.1152/ajpendo.00494.2012 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 107FK UT WOS:000316200100008 PM 23321478 ER PT J AU Moss, AK Hamarneh, SR Mohamed, MMR Ramasamy, S Yammine, H Patel, P Kaliannan, K Alam, SN Muhammad, N Moaven, O Teshager, A Malo, NS Narisawa, S Millan, JL Warren, HS Hohmann, E Malo, MS Hodin, RA AF Moss, Angela K. Hamarneh, Sulaiman R. Mohamed, Mussa M. Rafat Ramasamy, Sundaram Yammine, Halim Patel, Palak Kaliannan, Kanakaraju Alam, Sayeda N. Muhammad, Nur Moaven, Omeed Teshager, Abeba Malo, Nondita S. Narisawa, Sonoko Millan, Jose Luis Warren, H. Shaw Hohmann, Elizabeth Malo, Madhu S. Hodin, Richard A. TI Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE lipopolysaccharide; P2Y(6) pyrimidinergic receptor; intestinal loop model ID INFLAMMATORY-BOWEL-DISEASE; P2Y(6) RECEPTOR; KNOCKOUT MICE; NEUTROPHIL MIGRATION; SPONTANEOUS COLITIS; CROHNS-DISEASE; GUT MICROBIOTA; IN-VIVO; CELLS; EXPRESSION AB Uridine diphosphate (UDP) is a proinflammatory nucleotide implicated in inflammatory bowel disease. Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor capable of inhibiting intestinal inflammation. We used the malachite green assay to show that IAP dephosphorylates UDP. To study the anti-inflammatory effect of IAP, UDP or other proinflammatory ligands (LPS, flagellin, Pam3Cys, or TNF-alpha) in the presence or absence of IAP were applied to cell cultures, and IL-8 was measured. UDP caused dose-dependent increase in IL-8 release by immune cells and two gut epithelial cell lines, and IAP treatment abrogated IL-8 release. Costimulation with UDP and other inflammatory ligands resulted in a synergistic increase in IL-8 release, which was prevented by IAP treatment. In vivo, UDP in the presence or absence of IAP was instilled into a small intestinal loop model in wild-type and IAP-knockout mice. Luminal contents were applied to cell culture, and cytokine levels were measured in culture supernatant and intestinal tissue. UDP-treated luminal contents induced more inflammation on target cells, with a greater inflammatory response to contents from IAP-KO mice treated with UDP than from WT mice. Additionally, UDP treatment increased TNF-alpha levels in intestinal tissue of IAP-KO mice, and cotreatment with IAP reduced inflammation to control levels. Taken together, these studies show that IAP prevents inflammation caused by UDP alone and in combination with other ligands, and the anti-inflammatory effect of IAP against UDP persists in mouse small intestine. The benefits of IAP in intestinal disease may be partly due to inhibition of the proinflammatory activity of UDP. C1 [Moss, Angela K.; Hamarneh, Sulaiman R.; Mohamed, Mussa M. Rafat; Ramasamy, Sundaram; Yammine, Halim; Patel, Palak; Kaliannan, Kanakaraju; Alam, Sayeda N.; Muhammad, Nur; Moaven, Omeed; Teshager, Abeba; Malo, Nondita S.; Malo, Madhu S.; Hodin, Richard A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Narisawa, Sonoko; Millan, Jose Luis] Sanford Childrens Hlth Res Ctr, Burnham Inst Med Res, La Jolla, CA USA. [Warren, H. Shaw; Hohmann, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Moss, AK (reprint author), Massachusetts Gen Hosp, Dept Surg, GRB 4-425,55 Fruit St, Boston, MA 02114 USA. EM akmoss@partners.org RI kaliannan, kanakaraju/P-9094-2014; OI Moaven, Omeed/0000-0002-0560-0457; Kuhnen, Angela/0000-0003-4944-9143 FU National Institutes of Health [R01 DK-050623, R01 DK-047186, T32 CA-009535, AI-059010]; Shiners Hospital for Crippled Children [8720]; Grand Challenge Exploration Grant from the Gates Foundation FX This study was supported by National Institutes of Health Grants R01 DK-050623 (R. A. Hodin), R01 DK-047186 (R. A. Hodin), T32 CA-009535 (M. M. Bertagnolli), and AI-059010 (H. S. Warren), Shiners Hospital for Crippled Children Grant 8720 (H. S. Warren), and a Grand Challenge Exploration Grant from the Gates Foundation (M. S. Malo). NR 48 TC 14 Z9 15 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2013 VL 304 IS 6 BP G597 EP G604 DI 10.1152/ajpgi.00455.2012 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 107EV UT WOS:000316198500005 PM 23306083 ER PT J AU Huang, JV Lu, L Ye, SY Bergman, BC Sparagna, GC Sarraf, M Reusch, JEB Greyson, CR Schwartz, GG AF Huang, Janice V. Lu, Li Ye, Shuyu Bergman, Bryan C. Sparagna, Genevieve C. Sarraf, Mohammad Reusch, Jane E. B. Greyson, Clifford R. Schwartz, Gregory G. TI Impaired contractile recovery after low-flow myocardial ischemia in a porcine model of metabolic syndrome SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE metabolic syndrome; heart; ischemia; reperfusion; contractility; fatty acids; Akt; cardiolipin ID PYRUVATE-DEHYDROGENASE COMPLEX; CORONARY-ARTERY-DISEASE; DIET-INDUCED OBESITY; HIGH-FAT DIET; INSULIN-RESISTANCE; ISCHEMIA/REPERFUSION INJURY; NONDIABETIC PATIENTS; CARDIOVASCULAR RISK; GLUCOSE-METABOLISM; REPERFUSION INJURY AB Huang JV, Lu L, Ye S, Bergman BC, Sparagna GC, Sarraf M, Reusch JE, Greyson CR, Schwartz GG. Impaired contractile recovery after low-flow myocardial ischemia in a porcine model of metabolic syndrome. Am J Physiol Heart Circ Physiol 304: H861-H873, 2013. First published January 18, 2013; doi:10.1152/ajpheart.00535.2012.Clinical metabolic syndrome conveys a poor prognosis in patients with acute coronary syndrome, not fully accounted for by the extent of coronary atherosclerosis. To explain this observation, we determined whether postischemic myocardial contractile and metabolic function are impaired in a porcine dietary model of metabolic syndrome without atherosclerosis. Micropigs (n = 28) were assigned to a control diet (low fat, no added sugars) or an intervention diet (high saturated fat and simple sugars, no added cholesterol) for 7 mo. The intervention diet produced obesity, hypertension, dyslipidemia, and impaired glucose tolerance, but not atherosclerosis. Under open-chest, anesthetized conditions, pigs underwent 45 min of low-flow myocardial ischemia and 120 min of reperfusion. In both diet groups, contractile function was similar at baseline and declined similarly during ischemia. However, after 120 min of reperfusion, regional work recovered to 21 +/- 12% of baseline in metabolic syndrome pigs compared with 61 +/- 13% in control pigs (P = 0.01). Ischemiareperfusion caused a progressive decline in mechanical/metabolic efficiency (regional work/O-2 consumption) in metabolic syndrome hearts, but not in control hearts. Metabolic syndrome hearts demonstrated altered fatty acyl composition of cardiolipin and increased Akt phosphorylation in both ischemic and nonischemic regions, suggesting tonic activation. Metabolic syndrome hearts used more fatty acid than control hearts (P = 0.03). When fatty acid availability was restricted by prior insulin exposure, differences between groups in postischemic contractile recovery and mechanical/metabolic efficiency were eliminated. In conclusion, pigs with characteristics of metabolic syndrome demonstrate impaired contractile and metabolic recovery after low-flow myocardial ischemia. Contributory mechanisms may include remodeling of cardiolipin, abnormal activation of Akt, and excessive utilization of fatty acid substrates. C1 [Huang, Janice V.; Lu, Li; Ye, Shuyu; Sparagna, Genevieve C.; Sarraf, Mohammad; Greyson, Clifford R.; Schwartz, Gregory G.] Vet Affairs Med Ctr, Cardiol Sect, Denver, CO USA. [Huang, Janice V.; Lu, Li; Ye, Shuyu; Sarraf, Mohammad; Greyson, Clifford R.; Schwartz, Gregory G.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA. [Bergman, Bryan C.; Reusch, Jane E. B.] Univ Colorado, Sch Med, Div Endocrinol & Metab, Aurora, CO USA. [Sparagna, Genevieve C.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Reusch, Jane E. B.] Vet Affairs Med Ctr, Endocrinol & Metab Sect, Denver, CO USA. RP Schwartz, GG (reprint author), Denver Vet Affairs Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM Gregory.Schwartz@va.gov FU National Heart, Lung, and Blood Institute [HL-049944]; Medical Research Service of the Department of Veterans Affairs FX This work was supported by National Heart, Lung, and Blood Institute Grant HL-049944 (to G. G. Schwartz) and the Medical Research Service of the Department of Veterans Affairs. NR 63 TC 3 Z9 3 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2013 VL 304 IS 6 BP H861 EP H873 DI 10.1152/ajpheart.00535.2012 PG 13 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 107HM UT WOS:000316206400010 PM 23335793 ER PT J AU Patel, SS Patel, MS Goldfarb, M Ortega, A Ault, GT Kaiser, AM Senagore, AJ AF Patel, Supriya S. Patel, Madhukar S. Goldfarb, Melanie Ortega, Adrian Ault, Glenn T. Kaiser, Andreas M. Senagore, Anthony J. TI Elective versus emergency surgery for ulcerative colitis: a National Surgical Quality Improvement Program analysis SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Ulcerative colitis; Emergency; Elective; Surgery; Medical therapy ID POSTOPERATIVE COMPLICATIONS; COLECTOMY; RISK AB BACKGROUND: It is unclear whether advances in the medical management of ulcerative colitis (UC) have altered outcomes for medically intractable disease. Therefore, it is essential to understand the current impact of elective versus emergency surgery for UC. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to compare outcomes for elective versus emergency UC surgery between 2005 and 2010. RESULTS: Four thousand nine hundred sixty-two patients were eligible for study (94% elective and 6% emergent). Emergency surgery patients were significantly older and frequently underwent open surgery. Emergency cases were associated with a higher frequency of cardiac, pulmonary, and renal comorbidities; postoperative complications; longer hospital stays; and higher rates of return to the operating room. CONCLUSIONS: In the era of advanced UC medical therapy, the need for emergency surgery still exists and is associated with substantial morbidity and mortality. Data are needed to determine if earlier selection of surgery would be beneficial. (C) 2013 Elsevier Inc. All rights reserved. C1 [Patel, Supriya S.; Goldfarb, Melanie; Ortega, Adrian; Ault, Glenn T.; Kaiser, Andreas M.; Senagore, Anthony J.] Univ So Calif, Keck Sch Med, Div Colorectal Surg, Los Angeles, CA 90033 USA. [Patel, Madhukar S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Senagore, AJ (reprint author), Univ So Calif, Keck Sch Med, Div Colorectal Surg, 1441 Eastlake Ave,Suite 7418, Los Angeles, CA 90033 USA. EM anthony.senagore@med.usc.edu NR 11 TC 12 Z9 14 U1 1 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAR PY 2013 VL 205 IS 3 BP 333 EP 337 DI 10.1016/j.amjsurg.2012.10.014 PG 5 WC Surgery SC Surgery GA 103VZ UT WOS:000315948900039 PM 23369311 ER PT J AU Singh, NM Husain, S AF Singh, N. M. Husain, S. CA AST Infect Dis Community Practice TI Aspergillosis in Solid Organ Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Antifungal; aspergillosis; invasive fungal infections; opportunistic infection; pulmonary infection ID INVASIVE FUNGAL-INFECTIONS; COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELL; B LIPID COMPLEX; CHRONIC GRANULOMATOUS-DISEASE; SURVEILLANCE NETWORK TRANSNET; BRONCHOALVEOLAR LAVAGE FLUID; POLYMERASE-CHAIN-REACTION; AMPHOTERICIN-B; LUNG TRANSPLANTATION C1 [Singh, N. M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Singh, N. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Husain, S.] Univ Toronto, Univ Hlth Network Multiorgan Transplant, Toronto, ON, Canada. RP Singh, NM (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM nis5@pitt.edu FU Pfizer; Astellas FX The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Dr. Singh has received investigator initiated grant support from Pfizer and Astellas. Dr. Husain receives grant support from Pfizer and Astellas and is a consultant for Merck. NR 139 TC 49 Z9 49 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2013 VL 13 SU 4 SI SI BP 228 EP 241 DI 10.1111/ajt.12115 PG 14 WC Surgery; Transplantation SC Surgery; Transplantation GA 103HY UT WOS:000315907900025 PM 23465016 ER PT J AU Baddley, JW Forrest, GN AF Baddley, J. W. Forrest, G. N. CA AST Infect Dis Community Practice TI Cryptococcosis in Solid Organ Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Antifungal; cryptococcus; fungal infection; fungal meningitis; meningitis; pulmonary infection ID RECONSTITUTION INFLAMMATORY SYNDROME; INVASIVE FUNGAL-INFECTIONS; CALCINEURIN-INHIBITOR AGENTS; HEMATOPOIETIC STEM-CELL; B LIPID COMPLEX; AMPHOTERICIN-B; PULMONARY CRYPTOCOCCOSIS; NEOFORMANS INFECTION; PACIFIC-NORTHWEST; BRITISH-COLUMBIA C1 [Baddley, J. W.] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, J. W.] Birmingham Vet Affairs, Birmingham, AL USA. [Forrest, G. N.] Portland VA Med Ctr, Portland, OR USA. RP Baddley, JW (reprint author), Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. EM jbaddley@uab.edu NR 86 TC 18 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2013 VL 13 SU 4 SI SI BP 242 EP 249 DI 10.1111/ajt.12116 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 103HY UT WOS:000315907900026 PM 23465017 ER PT J AU Martin, SI Fishman, JA AF Martin, S. I. Fishman, J. A. CA AST Infect Dis Community Practice TI Pneumocystis Pneumonia in Solid Organ Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE opportunistic infection; Pneumocystis; pneumonia; posttransplant infection; trimethoprim sulfamethoxazole ID HUMAN-IMMUNODEFICIENCY-VIRUS; REAL-TIME PCR; BRONCHOALVEOLAR LAVAGE FLUID; BONE-MARROW-TRANSPLANTATION; BETA-D-GLUCAN; CARINII-PNEUMONIA; JIROVECII PNEUMONIA; IMMUNOCOMPROMISED PATIENTS; HIV-INFECTION; TRIMETHOPRIM-SULFAMETHOXAZOLE C1 [Martin, S. I.] Ohio State Univ, Wexner Med Ctr, Div Infect Dis, Columbus, OH 43210 USA. [Martin, S. I.] Ohio State Univ, Wexner Med Ctr, Comprehens Transplant Ctr, Columbus, OH 43210 USA. [Fishman, J. A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Fishman, J. A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. RP Martin, SI (reprint author), Ohio State Univ, Wexner Med Ctr, Div Infect Dis, Columbus, OH 43210 USA. EM stanley.martin@osumc.edu RI Martin, Stanley/E-3600-2011 NR 70 TC 26 Z9 26 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2013 VL 13 SU 4 SI SI BP 272 EP 279 DI 10.1111/ajt.12119 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 103HY UT WOS:000315907900029 PM 23465020 ER PT J AU Kotton, CN Hibberd, PL AF Kotton, C. N. Hibberd, P. L. CA AST Infect Dis Community Practice TI Travel Medicine and Transplant Tourism in Solid Organ Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Solid organ transplant; travel medicine; vaccinations; vaccines ID YELLOW-FEVER VACCINE; IMMUNIZATION PRACTICES ACIP; HEPATITIS-A VACCINATION; HIV-INFECTED PATIENTS; UNITED-STATES; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; ADVISORY-COMMITTEE; SINGLE-CENTER; RECIPIENTS C1 [Kotton, C. N.] Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, Boston, MA 02114 USA. [Kotton, C. N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hibberd, P. L.] Massachusetts Gen Hosp, Div Global Hlth, Boston, MA 02114 USA. [Hibberd, P. L.] Harvard Univ, Sch Med, Boston, MA USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, Boston, MA 02114 USA. EM ckotton@partners.org NR 61 TC 16 Z9 16 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2013 VL 13 SU 4 SI SI BP 337 EP 347 DI 10.1111/ajt.12125 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 103HY UT WOS:000315907900035 PM 23465026 ER PT J AU Burke, LG Joyce, N Baker, WE Biddinger, PD Dyer, KS Friedman, FD Imperato, J King, A Maciejko, TM Pearlmutter, MD Sayah, A Zane, RD Epstein, SK AF Burke, Laura G. Joyce, Nina Baker, William E. Biddinger, Paul D. Dyer, K. Sophia Friedman, Franklin D. Imperato, Jason King, Alice Maciejko, Thomas M. Pearlmutter, Mark D. Sayah, Assaad Zane, Richard D. Epstein, Stephen K. TI The Effect of an Ambulance Diversion Ban on Emergency Department Length of Stay and Ambulance Turnaround Time SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY JUN, 2011 CL Boston, MA SP Soc Acad Emergency Med ID VARIABLES; IMPACT AB Study objective: Massachusetts became the first state in the nation to ban ambulance diversion in 2009. It was feared that the diversion ban would lead to increased emergency department (ED) crowding and ambulance turnaround time. We seek to characterize the effect of a statewide ambulance diversion ban on ED length of stay and ambulance turnaround time at Boston-area EDs. Methods: We conducted a retrospective, pre-post observational analysis of 9 Boston-area hospital EDs before and after the ban. We used ED length of stay as a proxy for ED crowding. We compared hospitals individually and in aggregate to determine any changes in ED length of stay for admitted and discharged patients, ED volume, and turnaround time. Results: No ED experienced an increase in ED length of stay for admitted or discharged patients or ambulance turnaround time despite an increase in volume for several EDs. There was an overall 3.6% increase in ED volume in our sample, a 10.4-minute decrease in length of stay for admitted patients, and a 2.2-minute decrease in turnaround time. When we compared high- and low-diverting EDs separately, neither saw an increase in length of stay, and both saw a decrease in turnaround time. Conclusion: After the first statewide ambulance diversion ban, there was no increase in ED length of stay or ambulance turnaround time at 9 Boston-area EDs. Several hospitals actually experienced improvements in these outcome measures. Our results suggest that the ban did not worsen ED crowding or ambulance availability at Boston-area hospitals. [Ann Emerg Med. 2013;61:303-311.] C1 [Burke, Laura G.; Joyce, Nina; Epstein, Stephen K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Baker, William E.] Boston Med Ctr, Boston, MA USA. [Biddinger, Paul D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dyer, K. Sophia; Maciejko, Thomas M.] Boston Emergency Med Serv, Boston, MA USA. [Friedman, Franklin D.] Tufts Med Ctr, Boston, MA USA. [Imperato, Jason] Mt Auburn Hosp, Cambridge, MA USA. [King, Alice; Zane, Richard D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pearlmutter, Mark D.] St Elizabeths Med Ctr, Boston, MA USA. [Sayah, Assaad] Cambridge Hlth Alliance, Cambridge, MA USA. RP Burke, LG (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM lgburke@bidmc.harvard.edu RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017; OI Baker, William/0000-0002-4915-2553 NR 31 TC 9 Z9 9 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2013 VL 61 IS 3 BP 303 EP 311 DI 10.1016/j.annemergmed.2012.09.009 PG 9 WC Emergency Medicine SC Emergency Medicine GA 106TL UT WOS:000316167500012 PM 23352752 ER PT J AU Doran, KM Colucci, AC Hessler, RA Ngai, CK Williams, ND Wallach, AB Tanner, M Allen, MH Goldfrank, LR Wall, SP AF Doran, Kelly M. Colucci, Ashley C. Hessler, Robert A. Ngai, Calvin K. Williams, Nicholas D. Wallach, Andrew B. Tanner, Michael Allen, Machelle H. Goldfrank, Lewis R. Wall, Stephen P. TI An Intervention Connecting Low-Acuity Emergency Department Patients With Primary Care: Effect on Future Primary Care Linkage SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID FOLLOW-UP COMPLIANCE; PREVENTIVE CARE; MISSING DATA; UNINSURED EMERGENCY; PEDIATRIC EMERGENCY; ADVANCED STATISTICS; CLINICAL-RESEARCH; CONTROLLED-TRIAL; ACUTE ASTHMA; IMPROVE AB Study objective: Our objective is to determine whether a point-of-care intervention that navigates willing, low-acuity patients from the emergency department (ED) to a Primary Care Clinic will increase future primary care follow-up. Methods: We conducted a quasi-experimental trial at an urban safety net hospital. Adults presenting to the ED for select low-acuity problems were eligible. Patients were excluded if arriving by emergency medical services, if febrile, or if the triage nurse believed they required ED care. We enrolled 965 patients. Navigators escorted a subset of willing participants to the Primary Care Clinic (in the same hospital complex), where they were assigned a personal physician, were given an overview of clinic services, and received same-day clinic care. The primary outcome was Primary Care Clinic follow-up within 1 year of the index ED visit among patients having no previous primary care provider. Results: In the bivariate intention-to-treat analysis, 50.3% of intervention group patients versus 36.9% of control group patients with no previous primary care provider had at least 1 Primary Care Clinic follow-up visit in the year after the intervention. In the multivariable analysis, the absolute difference in having at least 1 Primary Care Clinic follow-up for the intervention group compared with the control group was 9.3% (95% confidence interval 2.2% to 16.3%). There was no significant difference in the number of future ED visits. Conclusion: A point-of-care intervention offering low-acuity ED patients the opportunity to alternatively be treated at the hospital's Primary Care Clinic resulted in increased future primary care follow-up compared with standard ED referral practices. [Ann Emerg Med. 2013;61:312-321.] C1 [Doran, Kelly M.] Yale Univ, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, New Haven, CT USA. [Doran, Kelly M.] US Dept Vet Affairs, New Haven, CT USA. [Colucci, Ashley C.; Hessler, Robert A.; Ngai, Calvin K.; Williams, Nicholas D.; Goldfrank, Lewis R.; Wall, Stephen P.] Bellevue Hosp Ctr, Dept Emergency Med, New York, NY 10016 USA. [Wallach, Andrew B.; Tanner, Michael] Bellevue Hosp Ctr, Div Gen Internal Med, New York, NY 10016 USA. [Allen, Machelle H.] Bellevue Hosp Ctr, Dept Obstet & Gynecol, New York, NY 10016 USA. NYU, Sch Med, New York, NY USA. RP Wall, SP (reprint author), Bellevue Hosp Ctr, Dept Emergency Med, New York, NY 10016 USA. EM stephen.wall@nyumc.org OI Wall, Stephen/0000-0003-3965-5074; Wallach, Andrew/0000-0003-4791-2376; Tanner, Michael/0000-0002-3012-8641 FU Commonwealth Fund FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. The Primary Care Access Project was supported by a grant from The Commonwealth Fund. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and the preparation, review, or approval of the article. NR 55 TC 12 Z9 12 U1 3 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2013 VL 61 IS 3 BP 312 EP 321 DI 10.1016/j.annemergmed.2012.10.021 PG 10 WC Emergency Medicine SC Emergency Medicine GA 106TL UT WOS:000316167500013 PM 23261312 ER PT J AU Akhter, M Runde, D Lee, J AF Akhter, Murtaza Runde, Dan Lee, Jarone TI Which Central Line Insertion Site Is the Least Prone to Infection? SO ANNALS OF EMERGENCY MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CENTRAL VENOUS CATHETERS; INTENSIVE-CARE-UNIT; COMPLICATIONS; PREVENTION; THERAPY C1 [Akhter, Murtaza] Emory Univ, Dept Emergency Med, Atlanta, GA 30322 USA. [Lee, Jarone] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Trauma, Cambridge, MA 02138 USA. [Lee, Jarone] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Surg, Cambridge, MA 02138 USA. [Lee, Jarone] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg Crit Care, Cambridge, MA 02138 USA. RP Akhter, M (reprint author), Emory Univ, Dept Emergency Med, Atlanta, GA 30322 USA. OI Lee, Jarone/0000-0002-4532-8523 NR 10 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2013 VL 61 IS 3 BP 362 EP 363 PG 2 WC Emergency Medicine SC Emergency Medicine GA 106TL UT WOS:000316167500023 PM 23141919 ER PT J AU Hodi, FS AF Hodi, F. S. TI NEW TOXICITIES OF IMMUNE CHECKPOINT MODULATORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Congress on Targeted Anticancer Therapies (TAT) CY MAR 04-06, 2013 CL Paris, FRANCE SP Natl Canc Inst, Ctr Canc Res, Novartis Pharma, AbbVie, Astex Pharmaceut, Boehringer Ingelheim Int, Roche, Servier, Pfizer Pharma, Sanofi-Aventis France C1 [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2013 VL 24 SU 1 BP 7 EP 7 PG 1 WC Oncology SC Oncology GA 106EN UT WOS:000316125600005 ER PT J AU Janne, PA AF Janne, P. A. TI GENE TRANSLOCATIONS AS TARGETS FOR TREATMENT SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Congress on Targeted Anticancer Therapies (TAT) CY MAR 04-06, 2013 CL Paris, FRANCE SP Natl Canc Inst, Ctr Canc Res, Novartis Pharma, AbbVie, Astex Pharmaceut, Boehringer Ingelheim Int, Roche, Servier, Pfizer Pharma, Sanofi-Aventis France C1 [Janne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2013 VL 24 SU 1 BP 12 EP 12 PG 1 WC Oncology SC Oncology GA 106EN UT WOS:000316125600022 ER PT J AU Wagner, AJ Zhang, YX Sicinska, E Czaplinski, JT Remillard, SP Demetri, GD Weng, S Debussche, L AF Wagner, A. J. Zhang, Y. X. Sicinska, E. Czaplinski, J. T. Remillard, S. P. Demetri, G. D. Weng, S. Debussche, L. TI POTENT INHIBITION OF HUMAN LIPOSARCOMA GROWTH AND SURVIVAL BY NOVEL MODULATORS OF THE MDM2-P53 INTERACTION SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Congress on Targeted Anticancer Therapies (TAT) CY MAR 04-06, 2013 CL Paris, FRANCE SP Natl Canc Inst, Ctr Canc Res, Novartis Pharma, AbbVie, Astex Pharmaceut, Boehringer Ingelheim Int, Roche, Servier, Pfizer Pharma, Sanofi-Aventis France C1 [Wagner, A. J.; Zhang, Y. X.; Sicinska, E.; Czaplinski, J. T.; Remillard, S. P.; Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weng, S.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Debussche, L.] Sanofi, Vitry Sur Seine, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2013 VL 24 SU 1 BP 14 EP 14 PG 1 WC Oncology SC Oncology GA 106EN UT WOS:000316125600033 ER PT J AU Meng, R Molife, LR de Mattos-Arruda, L Hollebecque, A Isakoff, SJ Roda, D Yan, Y Cervantes, A Soria, JC Mateo, J Argiles, G Bendell, JC AF Meng, R. Molife, L. R. de Mattos-Arruda, L. Hollebecque, A. Isakoff, S. J. Roda, D. Yan, Y. Cervantes, A. Soria, J. C. Mateo, J. Argiles, G. Bendell, J. C. TI PI3K/AKT ACTIVATION AND RESPONSE IN PHASE IB: AKT INHIBITOR GDC-0068 WITH DOCETAXEL (D) OR MFOLFOX6 (F) IN REFRACTORY SOLID TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Congress on Targeted Anticancer Therapies (TAT) CY MAR 04-06, 2013 CL Paris, FRANCE SP Natl Canc Inst, Ctr Canc Res, Novartis Pharma, AbbVie, Astex Pharmaceut, Boehringer Ingelheim Int, Roche, Servier, Pfizer Pharma, Sanofi-Aventis France C1 [Meng, R.; Yan, Y.] Genentech Inc, San Francisco, CA 94080 USA. [Molife, L. R.; Mateo, J.] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England. [de Mattos-Arruda, L.; Argiles, G.] Vall dHebron Univ Hosp, Barcelona, Spain. [Hollebecque, A.; Soria, J. C.] Inst Gustave Roussy, Villejuif, France. [Isakoff, S. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Roda, D.; Cervantes, A.] Univ Valen, Inst Hlth Res INCLIVA, Valencia, Spain. [Bendell, J. C.] Sarah Cannon Res Inst, Nashville, TN USA. RI Hollebecque, Antoine/M-2695-2013 OI Hollebecque, Antoine/0000-0003-2869-7551 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2013 VL 24 SU 1 BP 33 EP 33 PG 1 WC Oncology SC Oncology GA 106EN UT WOS:000316125600095 ER PT J AU Friedman, AD Hillman, RE Landau-Zemer, T Burns, JA Zeitels, SM AF Friedman, Aaron D. Hillman, Robert E. Landau-Zemer, Tali Burns, James A. Zeitels, Steven M. TI Voice Outcomes for Photoangiolytic KTP Laser Treatment of Early Glottic Cancer SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 18-19, 2012 CL San Diego, CA SP Amer Broncho Esophagol Assoc DE glottis; laryngeal cancer; laser; microlaryngoscopy; phonomicrosurgery; phonosurgery; vocal cord; vocal fold; voice ID VOCAL FOLD INFUSION; QUALITY-OF-LIFE; FUNCTIONAL OUTCOMES; LARYNGEAL-CANCER; CARCINOMA; CO2-LASER; RADIOTHERAPY; SURGERY; MANAGEMENT; CORDECTOMY AB Objectives: Surgery and radiotherapy routinely provide high cure rates in treating early glottic cancer. Therefore, key metrics for success are optimal voice outcome and preservation of future cancer treatment options. Remarkably, there is a paucity of pretreatment versus posttreatment voice outcome data. Angiolytic KTP (potassium titanyl phosphate) laser treatment of early glottic cancer with ultranarrow margins was initiated to better preserve vocal function. Given that effective oncological results have been achieved, it was hypothesized that this approach would also result in improved posttreatment measures of vocal function that more closely approximate historical norms than pretreatment values. Methods: Pretreatment and posttreatment voice outcome data were obtained for 92 patients (64 with T1 cancer and 28 with T2 cancer) who underwent 532-nm KTP laser treatment of early glottic cancer in a study design in which each patient essentially served as his or her own control. The evaluations included objective measures (acoustic and aerodynamic) and patients' self-assessments of vocal function (Voice-Related Quality of Life; V-RQOL). A series of mixed analyses of variance were conducted for all vocal function measures, with tumor stage and depth of invasion as the between-subjects variables and time (presurgery versus postsurgery) as the within-subject variable. Results: There were statistically significant (p <= 0.05) postoperative improvements for acoustic (perturbation and noise-to-harmonics ratio) and aerodynamic (subglottic pressure and vocal efficiency) measures of vocal function, as well as for V-RQOL assessment. Conclusions: Comprehensive pretreatment and posttreatment voice measures in a large patient cohort demonstrated that the KTP laser significantly improved postoperative vocal function in patients with early glottic cancer. Furthermore, radiotherapy was preserved as an oncological treatment option. C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 41 TC 7 Z9 7 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2013 VL 122 IS 3 BP 151 EP 158 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 108OG UT WOS:000316304700002 PM 23577566 ER PT J AU Jung, M Rhee, HS AF Jung, Minsoo Rhee, Hyun Sill TI Determinants of Community Capacity Influencing Residents' Health Status in Seoul, South Korea SO ASIA-PACIFIC JOURNAL OF PUBLIC HEALTH LA English DT Article DE community capacity; social capital; social determinants of health; resident; collective health status ID SELF-RATED HEALTH; PUBLIC-HEALTH; PARTICIPATION; PARTNERSHIPS; SENSE AB The effect of community capacity on health was evaluated by assessing the community via a questionnaire that included a capacity index in the social capital scale. The impact of the length of residence and the size and solidarity of networking on community capacity was also explored. The authors used logistic regression models controlling for sociodemographic factors and health behaviors among 1019 residents. The results indicate that lower community identity and social trust all led to statistically poor health levels. The manner in which members perceive their community was determined by cohesion, participation, length of residence, and the extent and strength of a member's network. Partnerships among and the subsequent organization of public resources by community members helped solidify the sense of community. With enhanced levels of sense of community, the collective level of health among residents can be readily and effectively improved. C1 [Jung, Minsoo] Korea Univ, Hlth Sci Res Inst, Seoul 136703, South Korea. [Jung, Minsoo] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rhee, Hyun Sill] Korea Univ, Seoul 136703, South Korea. RP Rhee, HS (reprint author), Korea Univ, Dept Healthcare Management, San1, Seoul 136703, South Korea. EM pridehyun@korea.ac.kr OI Jung, Minsoo/0000-0003-3317-6507 FU National Research Foundation of Korea; Korean Government [NRF-2011-357-E00028] FX This work was supported by National Research Foundation of Korea Grant funded by the Korean Government to Dr. Minsoo Jung (PI) (NRF-2011-357-E00028). NR 30 TC 4 Z9 4 U1 0 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1010-5395 J9 ASIA-PAC J PUBLIC HE JI Asia-Pac. J. Public Health PD MAR PY 2013 VL 25 IS 2 BP 199 EP 208 DI 10.1177/1010539512441819 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 112ZK UT WOS:000316634700009 PM 22500030 ER PT J AU Wilbur, DC Darragh, TM AF Wilbur, David C. Darragh, Teresa M. TI Harmony at LAST SO CANCER CYTOPATHOLOGY LA English DT Editorial Material ID TERMINOLOGY STANDARDIZATION PROJECT; OF-AMERICAN-PATHOLOGISTS; CERVICAL PATHOLOGY; CONSENSUS RECOMMENDATIONS; COLPOSCOPY; SOCIETY C1 [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Darragh, Teresa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Darragh, TM (reprint author), UCSF, Mt Zion Med Ctr, Dept Pathol, Box 1785,1600 Divisadero St,Room B618, San Francisco, CA 94115 USA. EM teresa.darragh@ucsf.edu NR 10 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD MAR PY 2013 VL 121 IS 3 BP 111 EP 115 DI 10.1002/cncy.21275 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 108AD UT WOS:000316261900002 PM 23408704 ER PT J AU Faquin, WC AF Faquin, William C. TI Can a gene-expression classifier with high negative predictive value solve the indeterminate thyroid fine-needle aspiration dilemma? SO CANCER CYTOPATHOLOGY LA English DT Editorial Material ID UNDETERMINED SIGNIFICANCE; COST-EFFECTIVENESS; NODULES; DIAGNOSIS; CYTOLOGY; MANAGEMENT AB The recent study by Alexander et al validates the effectiveness of the Afirma test, and suggests a potential ancillary role for this unique test when appropriately applied in the evaluation of thyroid nodules classified by fine-needle aspiration as indeterminate. Cancer (Cancer Cytopathol) 2013. (c) 2013 American Cancer Society C1 [Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org NR 22 TC 15 Z9 15 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD MAR PY 2013 VL 121 IS 3 BP 116 EP 119 DI 10.1002/cncy.21277 PG 4 WC Oncology; Pathology SC Oncology; Pathology GA 108AD UT WOS:000316261900003 PM 23364882 ER PT J AU Nathwani, BB Yang, TT Liao, JC AF Nathwani, Bhavik B. Yang, T. Tony Liao, Jung-Chi TI Towards a Subdiffraction View of Motor-Mediated Transport in Primary Cilia SO CELLULAR AND MOLECULAR BIOENGINEERING LA English DT Article DE Superresolution; STED; PALM; STORM; SIM; Intraflagellar transport; IFT; Kinesin; Dynein; Anterograde; Retrograde ID RETROGRADE INTRAFLAGELLAR TRANSPORT; LIGHT INTERMEDIATE CHAIN; LEFT-RIGHT ASYMMETRY; TUG-OF-WAR; HETEROTRIMERIC KINESIN-II; FLAGELLAR LENGTH CONTROL; MECKEL-GRUBER-SYNDROME; SMOOTH-MUSCLE-CELLS; CYTOPLASMIC DYNEIN; BASAL BODY AB Primary cilia play important sensory and signaling roles, with proteins responsible for functional activities delivered to the ciliary compartment via intraflagellar transport (IFT). IFT is a bidirectional microtubule-based motility mediated by molecular motors. This review aims to survey the course of motor-mediated transport in different stages of IFT and demonstrate the potential of using superresolution imaging in the studies of dynamic activities in primary cilia. Three major superresolution imaging techniques, i.e., STED, PALM/STORM, and SIM, are compared to illustrate their advantages and challenges. We overview the processes of recruitment of molecules to the base of a primary cilium, the assembly at the ciliary base, the passage through the transition zone, the anterograde IFT driven by kinesin, the turnover at the ciliary tip, the retrograde IFT driven by dynein, and the exit from the ciliary compartment. Given the small characteristic lengths of the molecules and structural elements involved in the motor-mediated transport and at the path of IFT, we further examine the advantages of using superresolution microscopy and the current development in subdiffraction studies of primary cilia. C1 [Nathwani, Bhavik B.; Yang, T. Tony; Liao, Jung-Chi] Columbia Univ, Dept Mech Engn, New York, NY 10027 USA. [Liao, Jung-Chi] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Nathwani, Bhavik B.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Nathwani, Bhavik B.] Harvard Univ, Sch Med, Dept Biochem & Mol Pharmacol, Boston, MA USA. [Nathwani, Bhavik B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Liao, JC (reprint author), Columbia Univ, Dept Mech Engn, New York, NY 10027 USA. EM Bhavik_Nathwani@dfci.harvard.edu; jcliao@columbia.edu RI Liao, Jung-Chi/B-3336-2014 FU NSF [CHE-0641523, CMMI-1125760] FX B.B. Nathwani, T.T. Yang, and J.-C. Liao were supported by NSF CHE-0641523 and CMMI-1125760. NR 148 TC 2 Z9 2 U1 1 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1865-5025 J9 CELL MOL BIOENG JI Cell. Mol. Bioeng. PD MAR PY 2013 VL 6 IS 1 SI SI BP 82 EP 97 DI 10.1007/s12195-013-0271-1 PG 16 WC Cell & Tissue Engineering; Biophysics; Cell Biology SC Cell Biology; Biophysics GA 109GY UT WOS:000316355800009 ER PT J AU Steen, DL Cannon, CP Lele, SS Rajapurkar, MM Mukhopadhyay, B Scirica, BM Murphy, SA Morrow, DA AF Steen, Dylan L. Cannon, Christopher P. Lele, Suhas S. Rajapurkar, Mohan M. Mukhopadhyay, Banibrata Scirica, Benjamin M. Murphy, Sabina A. Morrow, David A. TI Prognostic Evaluation of Catalytic Iron in Patients With Acute Coronary Syndromes SO CLINICAL CARDIOLOGY LA English DT Article ID BLEOMYCIN-DETECTABLE IRON; HEART-DISEASE; LIPID-PEROXIDATION; RADICAL GENERATION; REPERFUSION INJURY; METAL-IONS; ISCHEMIA; COPPER; CYTOCHROME-P-450; ATHEROSCLEROSIS AB Background: The potential of iron to generate reactive oxygen species has motivated a long-standing interest in whether excess iron is causally linked to atherosclerotic heart disease. Circulating catalytic iron (free iron) is that which is not bound to transferrin or ferritin and is available to generate reactive oxygen species that may have deleterious vascular effects. Hypothesis: We hypothesized that increased levels of catalytic iron would be associated with increased cardiovascular events. Methods: We investigated the association of catalytic iron with clinical outcomes in 1701 patients with unstable angina, nonST-segment elevation myocardial infarction (MI), or ST-segment elevation MI who were followed for a median of 10 months. All endpoints were adjudicated by a blinded Clinical End Points Committee. Results: The median catalytic iron level was significantly higher in those who died, 0.45 mu mol/L (0.37, 0.57), compared with survivors, 0.37 mu mol/L (0.31, 0.46; P = 0.016). Catalytic iron was associated with a stepwise increased risk of death, with the highest quartile at an almost 4-fold risk compared with baseline (hazard ratio: 3.94, P = 0.035), which persisted after adjustment for age, diabetes, prior MI, prior congestive heart failure, ST-segment deviation, creatinine clearance, B-type natriuretic peptide, smoking, and Killip class (adjusted hazard ratio: 3.97, P = 0.036). There was no association between catalytic iron and risk of MI, recurrent ischemia, heart failure, or bleeding. Conclusions: Increasing catalytic iron levels were associated with increased all-cause mortality. Although our findings suggest that catalytic iron is not likely to add to available tools as a routine biomarker for risk stratification of recurrent ischemic events, its association with mortality is intriguing and leaves open the question of whether cardiovascular therapeutics aimed at catalytic iron may be useful. The TIMI Study Group has received research grant support from the Muljibhai Patel Society for Research in Nephro-Urology. There are no other financial relationships, or conflicts of interest relevant to this manuscript to disclose. C1 [Steen, Dylan L.; Cannon, Christopher P.; Scirica, Benjamin M.; Murphy, Sabina A.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Lele, Suhas S.] Bhailal Amin Gen Hosp, Dept Cardiol, Vadodara, India. [Rajapurkar, Mohan M.] Muljibhai Patel Urol Hosp, Dept Nephrol, Nadiad, India. [Mukhopadhyay, Banibrata] Muljibhai Patel Urol Hosp, Dept Biochem, Nadiad, India. RP Steen, DL (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM steendy@gmail.com FU Muljibhai Patel Society for Research in Nephro-Urology FX The TIMI Study Group has received research grant support from the Muljibhai Patel Society for Research in Nephro-Urology. There are no other financial relationships, or conflicts of interest relevant to this manuscript to disclose. NR 27 TC 11 Z9 11 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2013 VL 36 IS 3 BP 139 EP 145 DI 10.1002/clc.22089 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 107PO UT WOS:000316230600005 PM 23377899 ER PT J AU Bis, S Tsao, H AF Bis, Sabina Tsao, Hensin TI Melanoma genetics: the other side SO CLINICS IN DERMATOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; RAF INHIBITOR RESISTANCE; KIT PROTEIN EXPRESSION; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; UVEAL MELANOMA; NRAS MUTATIONS; B-RAF; DIFFERENTIAL-DIAGNOSIS; ACTIVATING MUTATIONS AB Although melanoma has traditionally been regarded as a uniformly fatal malignancy, personalized treatment of this cancer relies on the recognition of its genetic heterogeneity and our ability to pharmacologically target these specific and recurrent changes. Recent advances in the treatment of melanoma have come from the understanding that melanoma is a large family of molecularly distinct diseases. Advances in melanoma genetics and new molecular technology, such as whole-exome and whole-genome sequencing, have lead to unprecedented progress in understanding the key oncogenes and signaling pathways involved in the pathogenesis and progression of melanoma. In addition, we have gained an appreciation for the complexity of such a system with numerous points of cross talk, which has partially impeded our current therapeutic strategies in patients with advanced melanoma. In this review, we focus on the novel discoveries in melanoma genetics and the potential for therapeutic options. (C) 2013 Published by Elsevier Inc. C1 [Bis, Sabina; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Melanoma & Pigmented Les Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. EM htsao@partners.org FU National Institutes of Health [K24 CA14920] FX Supported in part by National Institutes of Health Grant K24 CA14920 and by generous donors to the MGH Millennium Melanoma Fund. NR 60 TC 7 Z9 7 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD MAR-APR PY 2013 VL 31 IS 2 BP 148 EP 155 DI 10.1016/j.clindermatol.2012.08.003 PG 8 WC Dermatology SC Dermatology GA 105SY UT WOS:000316094000003 PM 23438378 ER PT J AU Schmidt, HD McGinty, JF West, AE Sadri-Vakili, G AF Schmidt, Heath D. McGinty, Jacqueline F. West, Anne E. Sadri-Vakili, Ghazaleh TI Epigenetics and Psychostimulant Addiction SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; BDNF MESSENGER-RNA; INDUCED BEHAVIORAL SENSITIZATION; MESOLIMBIC DOPAMINE SYSTEM; COCAINE-INDUCED PLASTICITY; MEDIAL PREFRONTAL CORTEX; GENE-EXPRESSION; NEUROTROPHIC FACTOR; NUCLEUS-ACCUMBENS; SYNAPTIC PLASTICITY AB Chronic drug exposure alters gene expression in the brain and produces long-term changes in neural networks that underlie compulsive drug taking and seeking. Exactly how drug-induced changes in synaptic plasticity and subsequent gene expression are translated into persistent neuroadaptations remains unclear. Emerging evidence suggests that complex drug-induced neuroadaptations in the brain are mediated by highly synchronized and dynamic patterns of gene regulation. Recently, it has become clear that epigenetic mechanisms contribute to drug-induced structural, synaptic, and behavioral plasticity by regulating expression of gene networks. Here we review how alterations in histone modifications, DNA methylation, and microRNAs regulate gene expression and contribute to psychostimulant addiction with a focus on the epigenetic mechanisms that regulate brain-derived neurotrophic factor (BDNF) expression following chronic cocaine exposure. Identifying epigenetic signatures that define psychostimulant addiction may lead to novel, efficacious treatments for drug craving and relapse. C1 [Schmidt, Heath D.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [McGinty, Jacqueline F.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [West, Anne E.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. [Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Schmidt, HD (reprint author), Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. EM hschmidt@mail.med.upenn.edu FU individual K01 award [DA030445]; [P50-DA15369]; [R01-DA03982]; [R01-DA022202]; [NS063953]; [DA022339] FX H.D.S. is supported by an individual K01 award (DA030445). J.F.M. is supported by P50-DA15369 and R01-DA03982. A. E. W is supported by R01-DA022202. G. S-V. is supported by NS063953 and DA022339. NR 163 TC 21 Z9 22 U1 3 U2 22 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD MAR PY 2013 VL 3 IS 3 AR a012047 DI 10.1101/cshperspect.a012047 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 111ZO UT WOS:000316561200007 PM 23359110 ER PT J AU Calkins, H AF Calkins, Hugh TI Arrhythmogenic Right Ventricular Dysplasia SO CURRENT PROBLEMS IN CARDIOLOGY LA English DT Review ID ELECTROCARDIOGRAPHIC FEATURES; CATHETER ABLATION; WOOLLY HAIR; CARDIOMYOPATHY; DYSPLASIA/CARDIOMYOPATHY; TACHYCARDIA; DISEASE; PLAKOGLOBIN; KERATODERMA; MUTATIONS AB Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy and is also called ARVD/C. In most cases, ARVD is inherited in an autosomal-dominant pattern and clinically is characterized by ventricular arrhythmias with an increased risk of sudden death. Although it is prominently a disease of the right ventricle (RV), involvement of the left ventricle is not uncommon. Pathologically, there is RV myocardial atrophy with thinning of the wall, aneurysm, and global RV dilatation. Genetic testing and magnetic resonance imaging of the RV are an increasing aspect of the diagnosis. Diagnosis relies on a scoring system with major or minor criteria. Prevention of sudden death is the primary goal of management Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and implantable cardioverter defibrillator are the mainstay of treatment of ARVD/C. (Curr Probl Carcliol 2013;38:103-123.) C1 [Calkins, Hugh] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Calkins, Hugh] Johns Hopkins Univ Hosp, Clin Electrophysiol Lab, Atrial Fibrillat Ctr, Arrhythmia Serv, Baltimore, MD 21287 USA. [Calkins, Hugh] Johns Hopkins Univ Hosp, Arrhythmogen Right Ventricular Dysplasia Program, Baltimore, MD 21287 USA. [Calkins, Hugh] Williams Coll, Williamstown, MA 01267 USA. [Calkins, Hugh] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Calkins, Hugh] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Calkins, Hugh] Univ Michigan, Ann Arbor, MI 48109 USA. RP Calkins, H (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 30 TC 18 Z9 18 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0146-2806 J9 CURR PROB CARDIOLOGY JI Curr. Probl. Cardiol. PD MAR PY 2013 VL 38 IS 3 BP 103 EP 123 DI 10.1016/j.cpcardiol.2012.12.002 PG 21 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 113FH UT WOS:000316651400002 PM 23453020 ER PT J AU Diercks, GR Iannuzzi, RA McCowen, K Sadow, PM AF Diercks, Gillian R. Iannuzzi, Ralph A. McCowen, Karen Sadow, Peter M. TI Dermoid Cyst of the Lateral Neck Associated with the Thyroid Gland: a Case Report and Review of the Literature SO ENDOCRINE PATHOLOGY LA English DT Review DE Dermoid cyst; Thyroid; Cervical mass ID CHILDREN; LESIONS; NODULE; HEAD AB Dermoid cysts are the most common teratomatous lesion; however, they infrequently arise in the head and neck region. Very rarely, dermoid cysts have been described in the thyrohyoid region, masquerading as a thyroid nodule. We describe the case of a 31-year-old woman with a lateral neck mass, associated with the thyroid gland inferiorly, which was excised and found to be a dermoid cyst. We then review the pathogenesis of dermoid cysts in this region, as well as review diagnosis and treatment of dermoid cysts of the head and neck. C1 [Diercks, Gillian R.; Iannuzzi, Ralph A.; Sadow, Peter M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Diercks, Gillian R.; Iannuzzi, Ralph A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Iannuzzi, Ralph A.] Harvard Vanguard Med Associates, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [McCowen, Karen] Harvard Univ, Sch Med, Dept Endocrinol, Boston, MA USA. [McCowen, Karen] Harvard Vanguard Med Associates, Dept Endocrinol, Boston, MA USA. [McCowen, Karen] Beth Israel Deaconess Med Ctr, Dept Endocrinol, Boston, MA 02215 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Diercks, GR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM gillian_diercks@meei.harvard.edu NR 10 TC 1 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD MAR PY 2013 VL 24 IS 1 BP 45 EP 48 DI 10.1007/s12022-013-9234-2 PG 4 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 109FG UT WOS:000316351000008 PM 23417694 ER PT J AU Guintivano, J Aryee, MJ Kaminsky, ZA AF Guintivano, Jerry Aryee, Martin J. Kaminsky, Zachary A. TI A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression SO EPIGENETICS LA English DT Article DE DNA methylation; neurons; glia; fluorescence activated cell sorting; epigenetics; cellular heterogeneity; microarray; age; brain region ID DNA METHYLATION SIGNATURES; CPG ISLAND SHORES; GENE-EXPRESSION; SYNAPTIC PLASTICITY; PREFRONTAL CORTEX; BIPOLAR DISORDER; AGING MOUSE; TISSUE; NEURONS; SCHIZOPHRENIA AB Brain cellular heterogeneity may bias DNA methylation patterns, influencing findings in psychiatric epigenetic studies. We performed fluorescence activated cell sorting (FACS) of neuronal nuclei and Illumina HM450 DNA methylation profiling in post mortem frontal cortex of 29 major depression subjects and 29 matched controls. We identify genomic features and ontologies enriched for cell type specific epigenetic variation. Using the top cell epigenotype specific (CETS) marks, we generated a publically available R package, "CETS," located at http://psychiatry.igm.jhmi.edu/kaminsky/software.htm that is capable of quantifying neuronal proportions and generating in silico neuronal profiles capable of removing cell type heterogeneity bias from DNA methylation data. We demonstrate a significant overlap in major depression DNA methylation associations between FACS separated and CETS model generated neuronal profiles relative to bulk profiles. CETS derived neuronal proportions correlated significantly with age in the frontal cortex and cerebellum and accounted for epigenetic variation between brain regions. CETS based control of cellular heterogeneity will enable more robust hypothesis testing in the brain. C1 [Guintivano, Jerry; Kaminsky, Zachary A.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Mood Disorders Ctr, Baltimore, MD 21205 USA. [Aryee, Martin J.] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Biostat, Baltimore, MD 21205 USA. [Aryee, Martin J.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Aryee, Martin J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kaminsky, ZA (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Mood Disorders Ctr, Baltimore, MD 21205 USA. EM zkamins1@jhmi.edu FU NIMH [1R21MH094771-01] FX Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders and the University of Maryland, Baltimore, MD. This work was funded by NIMH 1R21MH094771-01. We would like to further thank The Solomon R. and Rebecca D. Baker Foundation for their generous support of this research. NR 47 TC 84 Z9 84 U1 0 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD MAR PY 2013 VL 8 IS 3 BP 290 EP 302 DI 10.4161/epi.23924 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103NE UT WOS:000315923300007 PM 23426267 ER PT J AU Gallagher, A Tanaka, N Suzuki, N Liu, HS Thiele, EA Stufflebeam, SM AF Gallagher, Anne Tanaka, Naoaki Suzuki, Nao Liu, Hesheng Thiele, Elizabeth A. Stufflebeam, Steven M. TI Diffuse cerebral language representation in tuberous sclerosis complex SO EPILEPSY RESEARCH LA English DT Article DE Magnetoencephalography (MEG); Source localization; Distributed source model; Tuberous sclerosis complex (TSC); Epilepsy; Language ID SURFACE-BASED ANALYSIS; CORTICAL ACTIVITY; WORD RECOGNITION; BRAIN; MEG; MAGNETOENCEPHALOGRAPHY; RECONSTRUCTION; EPILEPSY; MODELS; CORTEX AB Introduction: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder affecting multiple organs, including the brain, and very often associated with epileptic activity. Language acquisition and development seems to be altered in a significant proportion of patients with TSC. In the present study, we used magnetoencephalography (MEG) to investigate spatiotemporal cerebral language processing in subjects with TSC and epilepsy during a reading semantic decision task, compared to healthy control participants. Methods: Fifteen patients with TSC and 31 healthy subjects performed a lexico-semantic decision task during MEG recording. Minimum-norm estimates (MNE) were computed allowing identification of cerebral generators of language evoked fields (EF) in each subject. Results: Source analysis of the language EF demonstrated early bilateral medial occipital activation (125 ms) followed by a fusiform gyrus activation around 135 ms. At 270 ms post stimuli presentation, a strong cerebral activation was recorded in the left basal temporal language area. Finally, cerebral activations were measured in Wernicke's area followed by Broca's area. The healthy control group showed larger and earlier language activations in Broca and Wernicke's areas compared to TSC patients. Moreover, cerebral activation from Broca's area was greater than activation from Wernicke's area in both groups, but this difference between anterior and posterior regions was smaller in the TSC group. Finally, the activation latency difference between Broca and Wernicke's areas was greater in healthy controls than in TSC patients, which shows that activations in these areas are more serial in control subjects compared to TSC patients in whom activations occur more simultaneously. Conclusions: This is the first study to investigate cerebral language pattern in patients with TSC. Compared to healthy controls, atypical neuromagnetic language responses may reflect cerebral reorganization in these patients in response to early epileptogenic activity or presence at birth of multiple brain lesions. (c) 2012 Elsevier B.V. All rights reserved. C1 [Gallagher, Anne; Tanaka, Naoaki; Suzuki, Nao; Liu, Hesheng; Stufflebeam, Steven M.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gallagher, Anne; Tanaka, Naoaki; Suzuki, Nao; Liu, Hesheng; Thiele, Elizabeth A.; Stufflebeam, Steven M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gallagher, Anne; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gallagher, A (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM anneg@nmr.mgh.harvard.edu OI Liu, Hesheng/0000-0002-7233-1509 FU National Center For Research Resources [S10RR031599]; National Institutes of Health [P41RR14075, RO1NS037462-07, R01NS069696]; Canadian Institute of Health Research (CIHR); Herscot Center for Tuberous Sclerosis Complex FX This research was supported by Award Number S10RR031599 from the National Center For Research Resources, and National Institutes of Health (P41RR14075, RO1NS037462-07, R01NS069696). This work was also supported by a scholarship by the Canadian Institute of Health Research (CIHR) awarded to Anne Gallagher, Ph.D. as well as by the Herscot Center for Tuberous Sclerosis Complex. NR 47 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD MAR PY 2013 VL 104 IS 1-2 BP 125 EP 133 DI 10.1016/j.eplepsyres.2012.09.011 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 111QH UT WOS:000316535300016 PM 23092910 ER PT J AU Lawson, EA Ackerman, KE Estella, NM Guereca, G Pierce, L Sluss, PM Bouxsein, ML Klibanski, A Misra, M AF Lawson, Elizabeth A. Ackerman, Kathryn E. Estella, Nara Mendes Guereca, Gabriela Pierce, Lisa Sluss, Patrick M. Bouxsein, Mary L. Klibanski, Anne Misra, Madhusmita TI Nocturnal oxytocin secretion is lower in amenorrheic athletes than nonathletes and associated with bone microarchitecture and finite element analysis parameters SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID QUANTITATIVE COMPUTED-TOMOGRAPHY; PLASMA OXYTOCIN; DISTAL RADIUS; HUMAN OSTEOBLASTS; EXERCISE; HORMONE; WOMEN; OSTEOPENIA; STRENGTH; FLUID AB Objective: Preclinical data indicate that oxytocin, a hormone produced in the hypothalamus and secreted into the peripheral circulation, is anabolic to bone. Oxytocin knockout mice have severe osteoporosis, and administration of oxytocin improves bone microarchitecture in these mice. Data suggest that exercise may modify oxytocin secretion, but this has not been studied in athletes in relation to bone. We therefore investigated oxytocin secretion and its association with bone microarchitecture and strength in young female athletes. Design: Cross-sectional study of 45 females, 14-21 years (15 amenorrheic athletes (AA), 15 eumenorrheic athletes (EA), and 15 nonathletes (NA)), of comparable bone age and BMI. Methods: We used high-resolution peripheral quantitative CT to assess bone microarchitecture and finite element analysis to estimate bone strength at the weight-bearing distal tibia and non-weight-bearing ultradistal radius. Serum samples were obtained every 60 min, 2300-0700 h, and pooled for an integrated measure of nocturnal oxytocin secretion. Midnight and 0700 h samples were used to assess diurnal variation of oxytocin. Results: Nocturnal oxytocin levels were lower in AA and EA than in NA. After controlling for estradiol, the difference in nocturnal oxytocin between AA and NA remained significant. Midnight and 0700 h oxytocin levels did not differ between groups. At the tibia and radius, AA had impaired microarchitecture compared with NA. In AA, nocturnal oxytocin correlated strongly with trabecular and cortical microarchitecture, particularly at the non-weight-bearing radius. In regression models that include known predictors of microarchitecture in AA, oxytocin accounted for a substantial portion of the variability in microarchitectural and strength parameters. Conclusions: Nocturnal oxytocin secretion is low in AA compared with NA and associated with site-dependent microarchitectural parameters. Oxytocin may contribute to hypoestrogenemic bone loss in AA. European Journal of Endocrinology 168 457-464 C1 [Lawson, Elizabeth A.; Ackerman, Kathryn E.; Estella, Nara Mendes; Guereca, Gabriela; Pierce, Lisa; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Lawson, Elizabeth A.; Ackerman, Kathryn E.; Estella, Nara Mendes; Guereca, Gabriela; Pierce, Lisa; Sluss, Patrick M.; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ackerman, Kathryn E.] Childrens Hosp, Dept Orthoped, Div Sports Med, Boston, MA 02115 USA. [Ackerman, Kathryn E.; Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02116 USA. EM ealawson@partners.org RI Mendes Estella, Nara/A-1469-2015 FU NIH [UL1 RR025758, RO1 HD060827, K23 MH092560]; Massachusetts General Hospital Claflin Distinguished Scholar Award FX NIH Grants UL1 RR025758, RO1 HD060827, and K23 MH092560; Massachusetts General Hospital Claflin Distinguished Scholar Award. NR 29 TC 12 Z9 12 U1 0 U2 5 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAR PY 2013 VL 168 IS 3 BP 457 EP 464 DI 10.1530/EJE-12-0869 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 110LG UT WOS:000316443000023 PM 23258269 ER PT J AU Benichou, G Tocco, G AF Benichou, Gilles Tocco, Georges TI The road to transplant tolerance is paved with good dendritic cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Editorial Material DE Allorecognition; Dendritic cells; Regulatory T (Treg) cells; Tolerance; Transplantation ID REGULATORY T-CELLS; CORNEAL TRANSPLANTATION; TRYPTOPHAN CATABOLISM; GRAFT-REJECTION; ALLOGRAFTS; ALLORECOGNITION; PATHWAYS; SKIN; ALLOREACTIVITY; MECHANISMS AB After transplantation, recipient T cells can recognize donor antigens either by interacting with MHC class II on donor bone marrow-derived cells (direct allorecognition), or by recognizing allogeneic peptides bound to self-MHC class II molecules on recipient antigen presenting cells (indirect allorecognition). The activation of pro-inflammatory T cells via either of these pathways leads to allograft rejection, so the suppression of both of these pathways is needed to achieve transplantation tolerance. A study in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43: 734746] shows that allogeneic dendritic cells (DCs) modified to either lack expression of CD80/86 or over-express indoleamine 2,3-dioxygenase (IDO) are able to inhibit direct and/or indirect alloresponses in vitro and in vivo in mice. Notably, both allorecognition pathways were suppressed by the coexpression of self- and allo-MHC molecules on semi-allogeneic DCs. This Commentary discusses the challenges and potential of using genetically-modified DCs to suppress alloreactivity in the context of transplant tolerance. C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Thier 807,55 Fruit St, Boston, MA 02114 USA. EM gbenichou@partners.org FU United States National Institute of Health (NIH) [R03AI09423, R21AI100278] FX The authors of this commentary are supported by the United States National Institute of Health (NIH grants R03AI09423 and R21AI100278). We would also like to thank Ms. Kate Capetta for her assistance with the preparation of this manuscript. NR 31 TC 3 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2013 VL 43 IS 3 BP 584 EP 588 DI 10.1002/eji.201343361 PG 5 WC Immunology SC Immunology GA 106JW UT WOS:000316140600004 PM 23412714 ER PT J AU Jilg, N Chung, RT AF Jilg, Nikolaus Chung, Raymond T. TI One more piece in the interleukin 28B gene puzzle? The case of hepatitis B SO HEPATOLOGY LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; C VIRUS-REPLICATION; INTERFERON-ALPHA; IL28B; INFECTION; THERAPY; POLYMORPHISMS; EXPRESSION; CLEARANCE; VARIANTS C1 [Jilg, Nikolaus; Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org NR 20 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2013 VL 57 IS 3 BP 870 EP 872 DI 10.1002/hep.26026 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099TG UT WOS:000315644200003 PM 22911469 ER PT J AU Kim, AY Nagami, EH Birch, CE Bowen, MJ Lauer, GM McGovern, BH AF Kim, Arthur Y. Nagami, Ellen H. Birch, Christopher E. Bowen, Melinda J. Lauer, Georg M. McGovern, Barbara H. TI A simple strategy to identify acute hepatitis C virus infection among newly incarcerated injection drug users SO HEPATOLOGY LA English DT Article ID UNITED-STATES; YOUNG-ADULTS; HCV INFECTION; RISK; METAANALYSIS; OPPORTUNITY; PREVALENCE; FACILITIES; PRISONERS; EPIDEMIC AB Acute hepatitis C virus (HCV) infection is underdiagnosed because most patients are asymptomatic. The majority of new infections occur among people who inject drugs (PWID), many of whom have a history of incarceration. In a previous pilot study, we identified symptomatic HCV cases, mainly among Caucasian inmates. We designed a cross-sectional study to evaluate whether risk factorbased screening of newly incarcerated inmates would enhance identification of asymptomatic acute HCV infection and elucidate any demographic shifts in HCV acquisition. From October 2006 to March 2008, 6,342 inmates underwent health assessments and 3,470 inmates (55%) were screened. The racial distribution was as follows: African American, 24.0%; Caucasian, 49.5%; Hispanic, 22.2%. One hundred seventy-one inmates (4.9%) were classified as high-risk. After further evaluation, 35 (20.5%) inmates were diagnosed with acute HCV with a mean age of 29 years; 62.9% were female and 91% were Caucasian. No African Americans were diagnosed with acute HCV. Our case-finding rate was 1.9 patients/month nearly a three-fold increase compared with our historical control period with a higher proportion of asymptomatic cases. We estimate a prevalence of approximate to 1.0% (95% confidence interval, 0.7%-1.4%) of acute HCV infections among newly incarcerated inmates. Conclusion: Within the correctional system, systematic screening based on risk factors successfully identifies acute HCV infection among PWID, including asymptomatic patients. Our data also reflect changing nationwide patterns of injection drug use that vary by age, ethnicity, and race, leading to a marked reduction of acute HCV infections among African Americans compared with non-Hispanic whites. The nationwide implementation of this simple low-cost strategy in prison-based settings could identify more than 7,000 acute HCV infections among PWID, provide insight into changing epidemiologic trends, and facilitate appropriate therapeutic and preventive interventions. (HEPATOLOGY 2013) C1 [Kim, Arthur Y.; Nagami, Ellen H.; Birch, Christopher E.; Bowen, Melinda J.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Kim, Arthur Y.; Nagami, Ellen H.; Birch, Christopher E.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Nagami, Ellen H.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Nagami, Ellen H.; Birch, Christopher E.; McGovern, Barbara H.] Lemuel Shattuck Hosp, Jamaica Plain, MA USA. [McGovern, Barbara H.] Tufts Med Sch, Boston, MA USA. [Bowen, Melinda J.] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Kim, AY (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Jackson 504, Boston, MA 02114 USA. EM akim1@partners.org FU National Institutes of Health National Institute of Allergy and Infectious Diseases Hepatitis C Cooperative Center [U19 AI066345]; Harvard University Center for AIDS Research [P30 AI060354]; [K23 AI054379] FX Supported by the National Institutes of Health National Institute of Allergy and Infectious Diseases Hepatitis C Cooperative Center (Grant U19 AI066345 [to G.M.L. and A.Y.K.] and Grant K23 AI054379 [to A.Y.K.]) and the Harvard University Center for AIDS Research (Grant P30 AI060354). NR 43 TC 10 Z9 10 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2013 VL 57 IS 3 BP 944 EP 952 DI 10.1002/hep.26113 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099TG UT WOS:000315644200015 PM 23111904 ER PT J AU Zhu, X Walton, RG Tian, L Luo, N Ho, SR Fu, Y Garvey, WT AF Zhu, X. Walton, R. G. Tian, L. Luo, N. Ho, S-R. Fu, Y. Garvey, W. T. TI Prostaglandin A(2) Enhances Cellular Insulin Sensitivity via a Mechanism that Involves the Orphan Nuclear Receptor NR4A3 SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE NR4A3; MINOR; insulin sensitivity; prostaglandin A(2); glucose transport; skeletal muscle; C2C12 cells ID 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); GLUCOSE-METABOLISM; ENDOTHELIAL-CELLS; GENE-EXPRESSION; INDUCTION; PRODUCTS; NUR77; IDENTIFICATION; TRANSCRIPTION; SUPERFAMILY AB We have previously reported that members of the NR4A family of orphan nuclear receptors can augment insulin's ability to stimulate glucose transport in adipocytes. In the current study, we endeavored to test for an insulin-sensitizing effect in muscle cells and to identify a potential transactivator. Lentiviral constructs were used to engineer both hyperexpression and shRNA silencing of NR4A3 in C2C12 myocytes. The NR4A3 hyper-expression construct led to a significant increase in glucose transport rates in the presence of maximal insulin while the NR4A3 knock-down exhibited a significant reduction in insulin-stimulated glucose transport rates. Consistently, insulin-mediated AKT phosphorylation was increased by NR4A3 hyperexpression and decreased following shRNA NR4A3 suppression. Then, we examined effects of prostaglandin A(2)(PGA(2)) on insulin action and NR4A3 transactivation. PGA(2) augmented insulin-stimulated glucose uptake in C2C12 myocytes and AKT phosphorylation after 12-h treatment, without significant effects on basal transport or basal AKT phosphorylation. More importantly, we demonstrated that PGA(2) led to a greater improvement in insulin-stimulated glucose rates in NR4A3 over-expressing C2C12 myocytes, when compared with Lac-Z controls stimulated with insulin and PGA(2). Moreover, the sensitizing effect of PGA(2) was significantly diminished in NR4A3 knockdown myocytes compared to scramble controls. These results show for the first time that: (i) PGA(2) augments insulin action in myocytes as manifested by enhanced stimulation of glucose transport and AKT phosphorylation; and (ii) the insulin sensitizing effect is dependent upon the orphan nuclear receptor NR4A3. C1 [Zhu, X.; Tian, L.; Ho, S-R.] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA. [Walton, R. G.; Luo, N.; Fu, Y.; Garvey, W. T.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. T.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Zhu, X (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA. EM xiaolin@uab.edu FU National Institutes of Health [DK-083562, DK-038764, HL-055782]; Merit Review program of the Department of Veterans Affairs; American Diabetes Association; UAB Diabetes Research and Training Center [P60-DK079626]; UAB Nutrition and Obesity Research Center [P30-DK56336] FX This work was supported from grants from the National Institutes of Health ( DK-083562, DK-038764, HL-055782 to W.T.G.), the Merit Review program of the Department of Veterans Affairs (W.T.G.), and the American Diabetes Association (Y.F.). We gratefully acknowledge the support of the research core facilities of the UAB Diabetes Research and Training Center (P60-DK079626) and the UAB Nutrition and Obesity Research Center (P30-DK56336). NR 29 TC 5 Z9 5 U1 0 U2 8 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD MAR PY 2013 VL 45 IS 3 BP 213 EP 220 DI 10.1055/s-0032-1327619 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 106ZZ UT WOS:000316185700005 PM 23104421 ER PT J AU Sakamoto, K Kim, MJ Rhoades, ER Allavena, RE Ehrt, S Wainwright, HC Russell, DG Rohde, KH AF Sakamoto, Kaori Kim, Mi Jeong Rhoades, Elizabeth R. Allavena, Rachel E. Ehrt, Sabine Wainwright, Helen C. Russell, David G. Rohde, Kyle H. TI Mycobacterial Trehalose Dimycolate Reprograms Macrophage Global Gene Expression and Activates Matrix Metalloproteinases SO INFECTION AND IMMUNITY LA English DT Article ID CORD FACTOR TREHALOSE-6,6'-DIMYCOLATE; NECROSIS-FACTOR-ALPHA; CELL-WALL LIPIDS; GRANULOMATOUS RESPONSE; TISSUE INHIBITORS; IMMUNE-RESPONSE; MYCOLIC ACIDS; IN-VIVO; ANTISENSE OLIGONUCLEOTIDES; TUBERCULOSIS INFECTION AB Trehalose 6,6'-dimycolate (TDM) is a cell wall glycolipid and an important virulence factor of mycobacteria. In order to study the role of TDM in the innate immune response to Mycobacterium tuberculosis, microarray analysis was used to examine gene regulation in murine bone marrow-derived macrophages in response to 90-mu m-diameter polystyrene microspheres coated with TDM. A large number of genes, particularly those involved in the immune response and macrophage function, were up-or downregulated in response to these TDM-coated beads compared to control beads. Genes involved in the immune response were specifically upregulated in a myeloid differentiation primary response gene 88 (MyD88)-dependent manner. The complexity of the transcriptional response also increased greatly between 2 and 24 h. Matrix metalloproteinases (MMPs) were significantly upregulated at both time points, and this was confirmed by quantitative real-time reverse transcription-PCR (RT-PCR). Using an in vivo Matrigel granuloma model, the presence and activity of MMP-9 were examined by immunohistochemistry and in situ zymography (ISZ), respectively. We found that TDM-coated beads induced MMP-9 expression and activity in Matrigel granulomas. Macrophages were primarily responsible for MMP-9 expression, as granulomas from neutrophil-depleted mice showed staining patterns similar to that for wild-type mice. The relevance of these observations to human disease is supported by the similar induction of MMP-9 in human caseous tuberculosis (TB) granulomas. Given that MMPs likely play an important role in both the construction and breakdown of tuberculous granulomas, our results suggest that TDM may drive MMP expression during TB pathogenesis. C1 [Sakamoto, Kaori] Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA. [Kim, Mi Jeong] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Immunobiol, Boston, MA 02115 USA. [Rhoades, Elizabeth R.] Cornell Univ, Cornell NanoScale Sci & Technol Facil, Ithaca, NY USA. [Allavena, Rachel E.] Univ Queensland, Sch Vet Sci, Gatton, Qld, Australia. [Ehrt, Sabine; Wainwright, Helen C.] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY USA. [Ehrt, Sabine; Wainwright, Helen C.] Univ Cape Town, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Russell, David G.] Cornell Univ, Dept Microbiol & Immunol, Ctr Vet Med, Ithaca, NY USA. [Rohde, Kyle H.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA. RP Sakamoto, K (reprint author), Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA. EM kaoris@uga.edu RI Allavena, Rachel /F-5720-2012; Russell, David/D-4533-2009 OI Allavena, Rachel /0000-0001-5126-7125; FU U.S. Public Health Service [HL055936, AI067027] FX This work was supported in part by U.S. Public Health Service grants HL055936 and AI067027 to D.G.R. NR 77 TC 14 Z9 16 U1 2 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2013 VL 81 IS 3 BP 764 EP 776 DI 10.1128/IAI.00906-12 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108RH UT WOS:000316313200018 PM 23264051 ER PT J AU Fiorentino, M Ding, H Blanchard, TG Czinn, SJ Sztein, MB Fasano, A AF Fiorentino, Maria Ding, Hua Blanchard, Thomas G. Czinn, Steven J. Sztein, Marcelo B. Fasano, Alessio TI Helicobacter pylori-Induced Disruption of Monolayer Permeability and Proinflammatory Cytokine Secretion in Polarized Human Gastric Epithelial Cells SO INFECTION AND IMMUNITY LA English DT Article ID CAG PATHOGENICITY ISLAND; IV SECRETION; TRANSEPITHELIAL MIGRATION; BARRIER FUNCTION; TRANSLOCATION; PROTEIN; KINASE; INTERLEUKIN-8; INDUCTION; INFECTION AB Helicobacter pylori infection of the stomach is related to the development of diverse gastric pathologies. The ability of H. pylori to compromise epithelial junctional complexes and to induce proinflammatory cytokines is believed to contribute to pathogenesis. The purpose of this study was to use an in vitro human gastric epithelial model to investigate the ability of H. pylori to affect permeability and the extent and polarity of the host inflammatory response. NCI-N87 monolayers were cocultured with live or heat-killed H. pylori or culture supernatants. Epithelial barrier function was measured by transepithelial electric resistance (TEER) analysis, diffusion of fluorescein isothiocyanate (FITC)-labeled markers, and immunostaining for tight junction proteins. Supernatants from both apical and basolateral chambers were tested for cytokine production by multiplex analysis. H. pylori caused a significant decrease in TEER, an increased passage of markers through the infected monolayer, and severe disruption and mislocalization of ZO-1 and claudin-1 proteins. Cell viability was not altered by H. pylori, indicating that loss of barrier function could be attributed to a breakdown of tight junction integrity. Significantly high levels of cytokine secretion were induced by either viable or heat-killed H. pylori. H. pylori affects monolayer permeability of polarized human gastric epithelial cells. Proinflammatory cytokines were secreted in a polarized manner, mostly basolaterally. Live bacteria are required for disruption of tight junctions but not for the induction of cytokine secretion. The NCI-N87 cell line provides an excellent model for the in vitro study of H. pylori pathogenesis and the epithelial cell host response to infection. C1 [Fiorentino, Maria; Fasano, Alessio] Univ Maryland, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA. [Fiorentino, Maria; Ding, Hua; Blanchard, Thomas G.; Czinn, Steven J.; Sztein, Marcelo B.; Fasano, Alessio] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Sztein, Marcelo B.] Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. RP Fasano, A (reprint author), Massachusetts Gen Hosp East, Mucosal Immunol & Biol Res Ctr, Charlestown, MA USA. EM afasano@partners.org OI Fiorentino, Maria R/0000-0001-5318-7313 FU NIAID (NIH, DHHS) grant (Cooperative Center for Translational Research in Human Immunology and Biodefense; CCHI) [U19 AI082655]; NIDDK (NIH, DHHS) [RO1 DK 45461] FX These studies were funded by NIAID (NIH, DHHS) grant U19 AI082655 (Cooperative Center for Translational Research in Human Immunology and Biodefense; CCHI) to M.B.S. and A.F. and by NIDDK (NIH, DHHS) grant RO1 DK 45461 to S.J.C. NR 38 TC 14 Z9 16 U1 1 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2013 VL 81 IS 3 BP 876 EP 883 DI 10.1128/IAI.01406 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108RH UT WOS:000316313200027 PM 23297384 ER PT J AU Sibila, O Restrepo, MI Anzueto, A AF Sibila, Oriol Restrepo, Marcos I. Anzueto, Antonio TI What is the Best Antimicrobial Treatment for Severe Community-Acquired Pneumonia (Including the Role of Steroids and Statins and Other Immunomodulatory Agents) SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Community-acquired infections; Pneumonia; Therapeutics; Intensive care unit ID RESISTANT STAPHYLOCOCCUS-AUREUS; BACTEREMIC PNEUMOCOCCAL PNEUMONIA; INTENSIVE-CARE-UNIT; CONVERTING-ENZYME-INHIBITOR; POPULATION-BASED COHORT; RESPIRATORY-TRACT INFECTIONS; RANDOMIZED CONTROLLED-TRIALS; SEVERE SEPSIS; PSEUDOMONAS-AERUGINOSA; CYTOKINE EXPRESSION AB Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases in the United States. The mortality rate due to severe CAP has shown little improvement over the past few years, with a rate as high as 50% mainly in patients admitted to intensive care units. Death and adverse outcomes from CAP result from a complex interplay between the pathogen and the host. Several therapies have been tested in patients with severe CAP in recent years. This article reviews recent data regarding different treatments including antimicrobials and adjunctive therapies in patients with severe CAP. C1 [Sibila, Oriol; Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Restrepo, Marcos I.; Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Anzueto, A (reprint author), South Texas Vet Hlth Care Syst, Audie L Murphy Div San Antonio, 7400 Merton Minter Blvd,11C6, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU Instituto de Salud Carlos III [BAE11/00102]; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR); Societat Catalana de Pneumologia (SOCAP); Fundacio Catalana de Pneumologia (FUCAP); National Heart, Lung, and Blood Institute [K23HL096054] FX Financial Support: Dr Sibila is supported by Instituto de Salud Carlos III (BAE11/00102), Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Societat Catalana de Pneumologia (SOCAP) and Fundacio Catalana de Pneumologia (FUCAP). Dr Restrepo's time is partially protected by Award Number K23HL096054 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. The funding agencies had no role in the preparation, review, or approval of the article. The views expressed in this article are those of the author and do not necessarily represent the views of the Department of Veterans Affairs. Conflicts of Interest: Dr Marcos I. Restrepo participated as a consultant in the data safety monitoring board for clinical trials run by Theravance, Trius, and Pfizer (Wyeth). Dr Antonio Anzueto has served in the speaker's bureaus of Pfizer, Boehringer Ingelheim, GlaxoSmithKline, Astra-Zeneca; and in the advisory board of Glaxo SmithKline, Boehringer Ingelheim, Bayer-Healthcare, and Pfizer. NR 110 TC 11 Z9 12 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 EI 1557-9824 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2013 VL 27 IS 1 BP 133 EP + DI 10.1016/j.idc.2012.11.014 PG 16 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 104YH UT WOS:000316032200011 PM 23398870 ER PT J AU Khalili, H Ananthakrishnan, AN Higuchi, LM Richter, JM Fuchs, CS Chan, AT AF Khalili, Hamed Ananthakrishnan, Ashwin N. Higuchi, Leslie M. Richter, James M. Fuchs, Charles S. Chan, Andrew T. TI Early Life Factors and Risk of Inflammatory Bowel Disease in Adulthood SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; Crohn's disease; ulcerative colitis; early life factors; breastfeeding; birth weight; prematurity; Nurses Health Study ID ULCERATIVE-COLITIS; CROHNS-DISEASE; INTESTINAL MICROBIOTA; RHEUMATOID-ARTHRITIS; OLMSTED COUNTY; PRETERM BIRTH; YOUNGER WOMEN; US WOMEN; CHILDHOOD; MORTALITY AB Background: Early life factors have been postulated to play a role in development of immune tolerance and intestinal microbiome, which in turn may influence the risk of inflammatory bowel disease. Methods: We conducted a prospective cohort study of 60,186 U. S. women enrolled since 1976 in the Nurses Health Study (NHS) I and 86,495 women enrolled since 1989 in the NHS II with no history of ulcerative colitis (UC) or Crohn's disease (CD). Information about breastfeeding, birth weight, and preterm birth were collected in 1992 in NHS I and 1991 in NHS II. Diagnoses of CD and UC were confirmed through review of medical records. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. Results: Among 146,681 women over 3,373,726 person-years of follow-up, we documented 248 cases of CD and 304 cases of UC through 2007 in NHS II and 2008 in NHS I. The median age of diagnosis was 51 for CD and 49 for UC. Compared with women who were not breastfed, women who were breastfed had multivariate-adjusted hazard ratios of 0.99 (95% confidence interval, 0.76-1.30) for CD and 1.03 (95% confidence interval, 0.81-1.32) for UC. Similarly, low or high birth weight and preterm birth were not significantly associated with risk of UC or CD. Conclusions: In 2 large prospective cohorts of U. S. women, we did not observe a significant association between early life factors including having been breastfed, birth weight, preterm birth, and risk of adult-onset UC and CD. (Inflamm Bowel Dis 2013;19:542-547) C1 [Khalili, Hamed; Ananthakrishnan, Ashwin N.; Richter, James M.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Ananthakrishnan, Ashwin N.; Higuchi, Leslie M.; Richter, James M.; Fuchs, Charles S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Higuchi, Leslie M.] Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-728A, Boston, MA 02114 USA. EM achan@partners.org FU Broad Medical Research Program of the Broad Foundation; Crohn's and Colitis Foundation of American and IBD Working Group; National Institute of Diabetes and Digestive and Kidney Diseases [K08 DK064256]; American Gastroenterological Association; [R01 CA137178]; [R01 CA050385]; [P01 CA87969]; [P30 DK043351] FX Funded by R01 CA137178, R01 CA050385, P01 CA87969, P30 DK043351, K08 DK064256, and the Broad Medical Research Program of the Broad Foundation. A. T. Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator. H. Khalili is supported by a career development award from the Crohn's and Colitis Foundation of American and IBD Working Group. L. M. Higuchi is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK064256). A. N. Ananthakrishnan is supported by a Research Scholars Award from the American Gastroenterological Association. A. T. Chan has served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, and Pfizer Inc. NR 36 TC 16 Z9 16 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAR PY 2013 VL 19 IS 3 BP 542 EP 547 DI 10.1097/MIB.0b013e31828132f8 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 110NG UT WOS:000316450200024 PM 23429446 ER PT J AU Melmed, GY Siegel, CA Spiegel, BM Allen, JI Cima, R Colombel, JF Dassopoulos, T Denson, LA Dudley-Brown, S Garb, A Hanauer, SB Kappelman, MD Lewis, JD Lynch, I Moynihan, A Rubin, DT Sartor, RB Schwartz, RM Wolf, DC Ullman, TA AF Melmed, Gil Y. Siegel, Corey Allan Spiegel, Brennan M. Allen, John I. Cima, Robert Colombel, Jean-Frederic Dassopoulos, Themistocles Denson, Lee A. Dudley-Brown, Sharon Garb, Andrew Hanauer, Stephen B. Kappelman, Michael D. Lewis, James D. Lynch, Isabelle Moynihan, Amy Rubin, David T. Sartor, R. Balfour Schwartz, Ronald M. Wolf, Douglas C. Ullman, Thomas A. TI Quality Indicators for Inflammatory Bowel Disease: Development of Process and Outcome Measures SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; Crohn's disease; ulcerative colitis; quality; quality indicators; quality of care; quality measures ID ULCERATIVE-COLITIS; CROHNS-DISEASE; ARTHRITIS CARE; OF-CARE; SET; MANAGEMENT; ADULTS; GUIDELINES; CHILDREN; EXPERTS AB Introduction: Variation in adherence to management guidelines for inflammatory bowel disease (IBD) suggests variable quality of care. Quality indicators (QIs) can be developed to measure the structure, processes, and outcomes of health care delivery. The RAND/UCLA appropriateness method was used to develop a set of process and outcome QIs to define quality of care for IBD. Methods: Guidelines and position papers for IBD published from 2006 to 2011 were reviewed for potential QIs, which were rated by a multidisciplinary panel. Potential process and outcome QIs were discussed at 3 moderated in-person meetings, with pre-meeting and post-meeting confidential electronic voting. Panelists rated the validity and feasibility of QIs on a 1 through 9 scale; disagreement was assessed using a validated index. QIs rated above 8 were selected for the final set. Results: More than 500 potential process QIs were extracted from guidelines. Following ratings and discussion by the first panel, 35 process QIs were selected for literature review. After the second panel, 10 process QIs were included in the final set. Candidate outcome QIs were then derived from physician, nurse, and patient input and ratings, in addition to outcomes associated with candidate process QIs. None of the top QIs exhibited disagreement. Conclusions: A set of QIs for IBD was developed with expert interpretation of the literature and multidisciplinary input. Outcome QIs focused largely on remission and quality of life, whereas process QIs were aimed at therapeutic optimization and patient safety. Evaluation of these QIs in clinical practice is needed to assess the correlation of performance on process QIs with performance on outcome QIs. (Inflamm Bowel Dis 2013;19:662-668) C1 [Melmed, Gil Y.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Melmed, Gil Y.; Spiegel, Brennan M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Siegel, Corey Allan; Moynihan, Amy] Dartmouth Hitchcock Med Ctr, Dept Gastroenterol, Lebanon, NH 03766 USA. [Siegel, Corey Allan; Moynihan, Amy] New Hampshire & Dartmouth Inst Hlth Policy & Clin, Hanover, NH USA. [Spiegel, Brennan M.] VA Greater Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Spiegel, Brennan M.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Spiegel, Brennan M.] UCLA VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Allen, John I.] Minnesota Gastroenterol, Dept Gastroenterol, Minneapolis, MN USA. [Cima, Robert] Mayo Clin, Dept Surg, Rochester, MN USA. [Colombel, Jean-Frederic] Icahn Sch Med Mt Sinai, New York, NY USA. [Dassopoulos, Themistocles] Washington Univ Sch Med, Dept Gastroenterol, St Louis, MO USA. [Denson, Lee A.] Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA. [Dudley-Brown, Sharon] Johns Hopkins Univ, JSch Med & Nursing, Baltimore, MD USA. [Garb, Andrew] Loeb & Loeb, Los Angeles, CA USA. [Hanauer, Stephen B.; Rubin, David T.] Univ Chicago, Dept Med & Gastroenterol, Chicago, IL 60637 USA. [Kappelman, Michael D.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Sartor, R. Balfour] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Sartor, R. Balfour] Univ N Carolina, Dept Microbiol, Chapel Hill, NC USA. [Sartor, R. Balfour] Univ N Carolina, Dept Immunol, Chapel Hill, NC USA. [Lewis, James D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lynch, Isabelle] VA San Francisco, Dept Gastroenterol, San Francisco, CA USA. [Schwartz, Ronald M.] Minnesota Gastroenterol, Minneapolis, MN USA. [Wolf, Douglas C.] Atlanta Gastroenterol Associates, Atlanta, GA USA. [Ullman, Thomas A.] Mt Sinai Sch Med, Dept Med, Dr Henry Janowitz Div Gastroenterol, New York, NY USA. RP Melmed, GY (reprint author), 8730 Alden Dr,203B, Los Angeles, CA 90048 USA. EM melmedg@cshs.org FU Crohn's and Colitis Foundation of America; Pfizer; Abbott Laboratories; Janssen Pharmaceuticals; Salix; UCB; Warner-Chilcott; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK078678, DK088957]; Shire; Centocor; Takeda; Janssen; Abbott Laboratories, Abbott Park, Illinois; Abbott Laboratories, Abbott Park, Paris; Abbott Laboratories, Abbott Park, France; Centocor, Malvern, PA; Falk Pharma, Freiburg, Germany; Given Imaging, Hamburg, Germany; Merck Co., Inc., NJ; Schering Plough Corporation, Kenilworth, NJ; Shire Pharmaceuticals, Wayne, PA; UCB Pharma; Abbott/Abvie; Prometheus FX Supported by the Crohn's and Colitis Foundation of America.; G. Y. Melmed: consultant (Janssen, Celgene, Amgen, Given Imaging), non-CME speaker (Abbott Laboratories, Prometheus Labs), and research support (Pfizer); co-chairs the Quality of Care committee of the CCFA.; C. A. Siegel serves as a consultant to Abbott Laboratories, Elan, Given Imaging, Janssen Pharmaceuticals, Millenium, Salix and UCB; received research support from Abbott Laboratories, Janssen Pharmaceuticals, Salix, UCB and Warner-Chilcott, and has delivered CME talks for Abbott Laboratories and Janssen Pharmaceuticals. Supported by Grant Number K23DK078678 from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Siegel is the Chair of the Quality of Care committee of the CCFA.; J. D. Lewis: served as a consultant for Amgen, Millennium Pharmaceuticals, and Abbott. He has served on a Data and Safety Monitoring Board for clinical trials sponsored by Pfizer. He has received research support from Shire, Centocor, and Takeda. He has provided expert opinion related to legal matters on behalf of Roche. Dr. Lewis is Chair of the Crohn's and Colitis Foundation of America's National Scientific Advisory Committee.; M. D. Kappelman: serves as a consultant to GlaxoSmithKline and Cubist, and has received research support from Janssen. Dr. Kappelman is supported by Grant Number DK088957 from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Kappelman is the Chair of the Professional Education Committee and a member of the Quality of Care committee of the CCFA.; J.-F. Colombel: Consultant: Abbott Laboratories, Abbott Park, Illinois; Amgen, Thousand Oaks, CA; Biogen Idec Inc, Cambridge, M; Boehringer-Ingelheim, Inc., Ridgefield, CT; Bristol Meyers Squibb, Princeton, NJ; Cellerix SL, Madrid, Spain; Chemocentryx, Inc., Mountain View, CA; Centocor, Malvern, PA; Cosmo Technologies, Ltd, Milan, Italy; Elan Pharmaceuticals, Inc., San Francisco, CA; Genentech, San Francisco, CA; Giuliani SPA, Milano, It; Given Imaging, Hamburg, Ge; Glaxo Smith Kline, Research Triangle Park, NC; Immune Pharmaceuticals Ltd., ISR; Merck & Co., Inc., NJ; Millenium Pharmaceuticals Inc., Cambridge, MA; Neovacs SA, Paris, F; Ocerra Therapeutics, Inc. (previously named Renovia, Inc.), San Diego, CA; Pfizer Inc., New York, NY; Prometheus, San Diego, CA; Sanofi, USA; Schering Plough Corporation, Kenilworth, NJ; Shire Pharmaceuticals, Wayne, PA; Synta Pharmaceutical Corporation, Lexington, MA; Takeda, Philadelphia, PE; Teva Pharmaceuticals, North Wales, PA and Petah Tikva, Israel; Therakos, Exton, PA; TXcell, Valbonne, France; UCB Pharma (previously named Celltech Therapeutics, Ltd), Atlanta, GA and Brussels, Belgium; Wyeth Pharmaceuticals, Collegeville, PA. Speakers fees: Abbott Laboratories, Abbott Park, Illinois and Paris, France; Centocor, Malvern, PA; Falk Pharma, Freiburg, Germany; Ferring, Denmark and Paris, France; Given Imaging, Hamburg, Germany; Merck & Co., Inc., NJ; Schering Plough Corporation, Kenilworth, NJ and Paris, France; Shire Pharmaceuticals, Wayne, PA; UCB Pharma, Atlanta GA and Brussels, Belgium and Paris, France.; D. T. Rubin: Consultant: Abbott/Abbvie, UCB, Janssen, Prometheus. Grant support: Abbott/Abvie, UCB, Prometheus, Salix. CCFA: Professional Education Committee member, Chair, Professional Membership Task Force. NR 29 TC 42 Z9 47 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAR PY 2013 VL 19 IS 3 BP 662 EP 668 DI 10.1097/mib.0b013e31828278a2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 110NG UT WOS:000316450200038 PM 23388547 ER PT J AU Siebert, U Wurm, J Gothe, RM Arvandi, M Vavricka, SR von Kanel, R Begre, S Sulz, MC Meyenberger, C Sagmeister, M AF Siebert, Uwe Wurm, Johannes Gothe, Raffaella Matteucci Arvandi, Marjan Vavricka, Stephan R. von Kaenel, Roland Begre, Stefan Sulz, Michael C. Meyenberger, Christa Sagmeister, Markus CA Swiss IBD Cohort Study Grp TI Predictors of Temporary and Permanent Work Disability in Patients With Inflammatory Bowel Disease: Results of the Swiss Inflammatory Bowel Disease Cohort Study SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; Crohn's disease; ulcerative colitis; disability; multivariate analysis ID QUALITY-OF-LIFE; CROHNS-DISEASE; HEALTH-CARE; EPIDEMIOLOGY; UNEMPLOYMENT; GERMANY; IMPACT; COST AB Background: Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. Methods: A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. Results: Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. Conclusions: We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability. (Inflamm Bowel Dis 2013; 19: 847-855) C1 [Siebert, Uwe; Wurm, Johannes; Gothe, Raffaella Matteucci; Arvandi, Marjan] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, A-6060 Hall In Tirol, Austria. [Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Publ Hlth Decis Modeling Hlth Technol Assessm, Innsbruck, Austria. [Sulz, Michael C.; Meyenberger, Christa; Sagmeister, Markus] Kantonsspital, Div Gastroenterol, St Gallen, Switzerland. [Vavricka, Stephan R.] Stadtspital Triemli, Div Gastroenterol, Zurich, Switzerland. [von Kaenel, Roland; Begre, Stefan] Univ Hosp Bern, Div Psychosomat Med, Dept Gen Internal Med, Inselspital, CH-3010 Bern, Switzerland. [von Kaenel, Roland; Begre, Stefan] Univ Bern, Bern, Switzerland. RP Siebert, U (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. EM public-health@umit.at RI Schappi, Michela/D-5363-2012; Rogler, Gerhard/O-5308-2015; OI Rogler, Gerhard/0000-0002-1733-9188; Tutuian, Radu/0000-0001-9182-2517; Mueller, Christoph/0000-0002-3921-8678 FU Swiss National Science Foundation [3347CO-108792]; Abbott, Switzerland; [320000-114009/1] FX Supported by a research grant from the Swiss National Science Foundation grant 3347CO-108792 (Swiss IBD Cohort) and 320000-114009/1 (to S. R. V.) and an unrestricted educational grant by Abbott, Switzerland. NR 24 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAR-APR PY 2013 VL 19 IS 4 BP 847 EP 855 DI 10.1097/MIB.0b013e31827f278e PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 110NT UT WOS:000316451600032 PM 23446333 ER PT J AU Gordon, BR Hurst, DS Fornadley, JA Hunsaker, DH AF Gordon, Bruce R. Hurst, David S. Fornadley, John A. Hunsaker, Darrell H. TI Safety of intradermal skin tests for inhalants and foods: a prospective study SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE intradermal skin tests; skin test safety; anaphylaxis; non-IgE-mediated food allergy; food allergy; inhalant allergy; subcutaneous immunotherapy ID SYSTEMIC REACTIONS; PREDICTING RESPONSE; NASAL PROVOCATION; ADVERSE-REACTIONS; AMERICAN-ACADEMY; DOUBLE-BLIND; ALLERGY; IMMUNOTHERAPY; PRICK; AEROALLERGENS AB Background Intradermal skin testing is a useful allergy diagnostic tool. Although considered safe when properly performed, systemic reactions have been reported. This is the first large, prospective study to record and evaluate all systemic reactions from intradermal skin testing (IDT) to inhalant or food antigens. Methods A 24-month prospective study by 40 physician practices, recording all IDT tests, including reactions, symptoms, severity, time after injection, and reaction treatments. Results Eighty systemic reactions (22 major) occurred among 20,530 patients (878,583 wheals). Nine had epinephrine treatment, 4 were observed in an emergency department, and there were no hospitalizations or fatalities. The overall systemic reaction risk was 0.009%. The risk of having a major reaction was 0.003%, or 1 reaction per 933 patients. Conclusion Intradermal skin tests for inhalants or foods, when performed with appropriate precautions, have a safety profile comparable to skin prick tests. C1 [Gordon, Bruce R.] Cape Cod Hosp, Dept Otolaryngol, Hyannis, MA USA. [Gordon, Bruce R.] Harvard Univ, Dept Laryngol & Otol, Cambridge, MA 02138 USA. [Gordon, Bruce R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hurst, David S.] Tufts Univ, Dept Otolaryngol, Boston, MA 02111 USA. [Fornadley, John A.] Penn State Univ, Dept Surg, Hershey, PA USA. [Hunsaker, Darrell H.] USN, Dept Otolaryngol, Med Ctr, San Diego, CA 92152 USA. RP Gordon, BR (reprint author), Cape Cod ENT, 65 Cedar St, Hyannis, MA 02601 USA. EM docbruce@comcast.net FU American Academy of Otolaryngic Allergy Foundation FX Funding sources for the study: American Academy of Otolaryngic Allergy Foundation. NR 34 TC 4 Z9 4 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD MAR PY 2013 VL 3 IS 3 BP 171 EP 176 DI 10.1002/alr.21091 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 108BE UT WOS:000316265000002 PM 23044726 ER PT J AU Adappa, ND Howland, TJ Palmer, JN Kennedy, DW Doghramji, L Lysenko, A Reed, DR Lee, RJ Cohen, NA AF Adappa, Nithin D. Howland, Timothy J. Palmer, James N. Kennedy, David W. Doghramji, Laurel Lysenko, Anna Reed, Danielle R. Lee, Robert J. Cohen, Noam A. TI Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE innate immunity; antimicrobial; nitric oxide; mucociliary clearance; endoscopic sinus surgery ID SOLITARY CHEMOSENSORY CELLS; ENDOSCOPIC SINUS SURGERY; PHENYLTHIOCARBAMIDE; BIOFILMS; IMPACT; LONG AB Background We recently demonstrated the bitter taste receptor T2R38 upregulates sinonasal mucosal innate defense in response to gram-negative quorum-sensing molecules through increased nitric oxide production and mucociliary clearance. T2R38 was initially identified in the quest to understand the variability in bitter taste perception to the compound phenylthiocarbamide (PTC) and demonstrated to have polymorphisms generating diplotypes dividing people into PTC supertasters, heterozygotes (with variable PTC detection), and nontasters. We have further demonstrated that sinonasal epithelial cultures derived from supertasters significantly increase innate defenses in response to gram-negative quorum-sensing molecules compared with sinonasal cultures derived from heterozygotes and nontaster individuals. Based on this data, we hypothesize that supertasters are less likely to require sinus surgery compared with heterozygous or nontasters and that supertasters have improved surgical outcomes. Methods Banked sinonasal tissue samples from patients who had undergone primary functional endoscopic sinus surgery at the University of Pennsylvania or the Philadelphia Veterans Affairs Medical Center were genotyped for T2R38 and compared to the expected population distribution. Necessity for additional antibiotic therapy following the postoperative healing time frame was evaluated. Results A total of 28 patients were included in the study. Only 1 supertaster was identified (expected 5.6, p < 0.043). Additionally, 14 heterozygous and 13 nontaster patients were identified. Conclusion This pilot study investigating the genetics of the bitter taste receptor T2R38 in the context of primary sinonasal surgery demonstrates supertaster patients are less likely to need surgical intervention for chronic rhinosinusitis. Additional study is necessary to ascertain postsurgical outcomes. C1 [Adappa, Nithin D.; Howland, Timothy J.; Palmer, James N.; Kennedy, David W.; Doghramji, Laurel; Lee, Robert J.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Lysenko, Anna; Reed, Danielle R.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM noam.cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Reed, Danielle/0000-0002-4374-6107; Lee, Robert/0000-0001-5826-6686 NR 16 TC 31 Z9 31 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD MAR PY 2013 VL 3 IS 3 BP 184 EP 187 DI 10.1002/alr.21140 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 108BE UT WOS:000316265000004 PM 23322450 ER PT J AU Thomas, ML Brown, GG Gur, RC Hansen, JA Nock, MK Heeringa, S Ursano, RJ Stein, MB AF Thomas, Michael L. Brown, Gregory G. Gur, Ruben C. Hansen, John A. Nock, Matthew K. Heeringa, Steven Ursano, Robert J. Stein, Murray B. TI Parallel psychometric and cognitive modeling analyses of the Penn Face Memory Test in the Army Study to Assess Risk and Resilience in Servicemembers SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Psychometric modeling; Item response theory; Cognitive modeling; Penn Face Memory Test; Army Study to Assess Risk and Resilience in Servicemembers ID MEDIAL TEMPORAL-LOBE; ITEM RESPONSE THEORY; CEREBRAL BLOOD-FLOW; RECOGNITION MEMORY; CONSTRUCT-VALIDITY; SIGNAL-DETECTION; INDIVIDUAL-DIFFERENCES; VALIDATION; RECOLLECTION; PSYCHOLOGY AB Objective: The psychometric properties of the Penn Face Memory Test (PFMT) were investigated in a large sample (4,236 participants) of U.S. Army Soldiers undergoing computerized neurocognitive testing. Data were drawn from the initial phase of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), a large-scale study directed towards identifying risk and resilience factors for suicidal behavior and other stress-related disorders in Army Soldiers. In this paper, we report parallel psychometric and cognitive modeling analyses of the PFMT to determine whether ability estimates derived from the measure are precise and valid indicators of memory in the Army STARRS sample. Method: Single-sample cross-validation methodology combined with exploratory factor and multidimensional item response theory techniques were used to explore the latent structure of the PFMT. To help resolve rotational indeterminacy of the exploratory solution, latent constructs were aligned with parameter estimates derived from an unequal-variance signal detection model. Results: Analyses suggest that the PFMT measures two distinct latent constructs, one associated with memory strength and one associated with response bias, and that test scores are generally precise indicators of ability for the majority of Army STARRS participants. Conclusions: These findings support the use of the PFMT as a measure of major constructs related to recognition memory and have implications for further cognitivepsychometric model development. C1 [Thomas, Michael L.; Brown, Gregory G.; Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Brown, Gregory G.] VA San Diego Healthcare Syst, San Diego, CA USA. [Gur, Ruben C.; Hansen, John A.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Ruben C.; Hansen, John A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Heeringa, Steven] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Brown, GG (reprint author), San Diego VA Med Ctr, Psychol Serv 116B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM gbrown@ucsd.edu FU Department of the Army; U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH) [U01MH087981] FX Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement U01MH087981 with the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH). The contents are solely the responsibility of the authors and do not necessarily represent the views of the Department of Health and Human Services, NIMH, the Department of the Army, or the Department of Defense. NR 70 TC 8 Z9 8 U1 14 U2 28 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1380-3395 EI 1744-411X J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD MAR 1 PY 2013 VL 35 IS 3 BP 225 EP 245 DI 10.1080/13803395.2012.762974 PG 21 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 104IM UT WOS:000315985900001 PM 23383967 ER PT J AU Melrose, RJ Harwood, D Khoo, T Mandelkern, M Sultzer, DL AF Melrose, Rebecca J. Harwood, Dylan Khoo, Theresa Mandelkern, Mark Sultzer, David L. TI Association between cerebral metabolism and Rey-Osterrieth Complex Figure Test performance in Alzheimer's disease SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Alzheimer's disease; ReyOsterrieth Complex Figure; Fluorodeoxyglucose positron emission tomography; Visuospatial; Construction ID CLOCK DRAWING TEST; PREDICT INSTRUMENTAL ACTIVITIES; MILD COGNITIVE IMPAIRMENT; FUNCTIONAL ABILITIES; BLOOD-FLOW; BRAIN; DEMENTIA; DISTURBANCES; OBJECT; DIAGNOSIS AB The copy condition of the ReyOsterrieth Complex Figure (ROCF) is sensitive to Alzheimer's disease (AD) pathology, but its neural correlates remain unclear. We used fluorodeoxyglucose positron emission tomography (FDGPET) to elucidate this association in 77 patients with probable AD. We observed a correlation between ROCF and metabolic rate of bilateral temporalparietal cortex and occipital lobe, and right frontal lobe. Global and local elements of the ROCF correlated with metabolic rate of these same regions. The copy approach correlated with right lateral temporal cortex. The ROCF appears reflective of posterior temporalparietal cortex functioning, highlighting the role of visuospatial processing in constructional abilities in AD. C1 [Melrose, Rebecca J.; Harwood, Dylan; Khoo, Theresa; Sultzer, David L.] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA. [Melrose, Rebecca J.; Harwood, Dylan; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Mandelkern, Mark] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Melrose, RJ (reprint author), West Los Angeles VA Healthcare Syst, Bldg 401,Room A209,11301 Wilshire Blvd,116AE, Los Angeles, CA 90073 USA. EM rjmelrose@ucla.edu FU Department of Veterans Affairs; National Institutes of Health (NIH) [R01 MH56031]; Forest Research Institute FX Support was provided by the Department of Veterans Affairs (Merit Review to D. Sultzer and Career Development Award to R. Melrose) and National Institutes of Health (NIH; R01 MH56031). David Sultzer has received research grant support from Forest Research Institute. Potential conflicts to study participants were disclosed. NR 61 TC 6 Z9 6 U1 5 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD MAR 1 PY 2013 VL 35 IS 3 BP 246 EP 258 DI 10.1080/13803395.2012.763113 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 104IM UT WOS:000315985900002 PM 23387510 ER PT J AU Penedo, FJ Benedict, C Zhou, ES Rasheed, M Traeger, L Kava, BR Soloway, M Czaja, S Antoni, MH AF Penedo, Frank J. Benedict, Catherine Zhou, Eric S. Rasheed, Mikal Traeger, Lara Kava, Bruce R. Soloway, Mark Czaja, Sara Antoni, Michael H. TI Association of Stress Management Skills and Perceived Stress with Physical and Emotional Well-Being Among Advanced Prostrate Cancer Survivors Following Androgen Deprivation Treatment SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE Prostatic neoplasms; Stress management; Health related quality of life; Physical functioning; Emotional well-being; Prostate cancer ID QUALITY-OF-LIFE; LOCALIZED PROSTATE-CANCER; HEALTH SURVEY SF-36; RADICAL PROSTATECTOMY; SEXUAL FUNCTION; MEN; CARCINOMA; OUTCOMES; SPOUSES; INTERVENTION AB Advanced prostate cancer (APC) is associated with disruptions that compromise health related quality of life (HRQOL). Treatment often includes androgendeprivation therapy (ADT), which results in a range of side effects (e.g., fatigue, urinary dysfunction) that further impact HRQOL. Despite these challenges, there are limited evaluations of the impact of stress and stress management skills on HRQOL among APC survivors on ADT. This study evaluated relationships among stress, stress management skills, and HRQOL, and it was hypothesized that better stress management skills would relate to greater physical and emotional well-being by mitigating perceived stress levels. Participants (N = 77) were 69.7 years old (SD = 9.8), 18.6 months post-treatment (SD = 17.5), and ethnically diverse (65 % Non-Hispanic White, 13 % Hispanic, 21 % African-American). Measures included the Measure of Current Status for stress management skills, the Perceived Stress Scale for perceived stress, and the Medical Outcomes Study-Short Form (MOS SF-36; physical functioning and emotional well-being subscales) for HRQOL. Direct effects and mediation models were evaluated to determine the relationships between perceived stress, stress management skills, and HRQOL domains, controlling for relevant covariates. Stress management skills and perceived stress were significantly associated with physical functioning (beta = .24, p < .05 and beta = -.43, p < .01, respectively) and emotional well-being (beta = .35, p < .01 and beta = -.64, p < .01, respectively). Regression analyses supported the hypothesis that reduced perceived stress mediated the relationship between stress management skills and both physical functioning and emotional well-being. These results demonstrate that one way stress management skills may impact HRQOL is by lessening ongoing perceptions of stress. C1 [Penedo, Frank J.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Benedict, Catherine; Zhou, Eric S.; Rasheed, Mikal; Antoni, Michael H.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Traeger, Lara] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kava, Bruce R.; Soloway, Mark] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Czaja, Sara] Univ Miami, Dept Psychiat & Behav Sci, Miami, FL USA. [Antoni, Michael H.] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL USA. RP Benedict, C (reprint author), Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. EM cbenedict@psy.miami.edu NR 40 TC 10 Z9 10 U1 1 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD MAR PY 2013 VL 20 IS 1 BP 25 EP 32 DI 10.1007/s10880-012-9308-1 PG 8 WC Psychology, Clinical SC Psychology GA 107OU UT WOS:000316228500003 PM 22739661 ER PT J AU Cai, WL Zhang, D Lee, JG Shirai, Y Kim, SH Yoshida, H AF Cai, Wenli Zhang, Da Lee, June-Goo Shirai, Yu Kim, Se Hyung Yoshida, Hiroyuki TI Dual-Energy Index Value of Luminal Air in Fecal-Tagging Computed Tomography Colonography: Findings and Impact on Electronic Cleansing SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CT colonography; dual-energy computed tomography; fecal-tagging dual-energy CTC; electronic cleansing ID BEAM HARDENING CORRECTION; CT COLONOGRAPHY; EXPERIENCE; ARTIFACT AB Purpose: The purpose of our study was to measure the dual-energy index (DEI) value of colonic luminal air in both phantom and clinical fecal-tagging dual-energy computed tomography (CT) colonography (DE-CTC) images and to demonstrate its impact on dual-energy electronic cleansing. Methods: For the phantom study, a custom-ordered colon phantom was scanned by a dual-energy CT scanner (SOMATON Definition Flash; Siemens Healthcare, Forchheim, Germany) at two photon energies: 80 and 140 kVp. Before imaging, the phantom was filled with a 300-mL mixture of simulated fecal materials tagged by a nonionic iodinated contrast agent at three contrast concentrations: 20, 40, and 60 mg/mL. Ten regions-of-interest (ROIs) were randomly placed in each of the colonic luminal air, abdominal fat, bony structure, and tagged material in each scan. For the clinical study, 22 DE-CTC (80 and 140 kVp) patient cases were collected, who underwent a low-fiber, low-residue diet bowel preparation and orally administered iodine-based fecal tagging. Twenty ROIs were randomly placed in each of the colonic luminal air, abdominal fat, abdominal soft tissue, and tagged fecal material in each scan. For each ROI, the mean CT values in both 80- and 140-kVp images were measured, and then its DEI was calculated. Results: In the phantom study, the mean DEI values of luminal air were 0.270, 0.298, 0.386, and 0.402 for the four groups of tagging conditions: no tagged material and tagged with three groups of contrast concentrations at 20, 40, and 60 mg/mL. In the clinical study, the mean DEI values were 0.341, -0.012, -0.002, and 0.188 for colonic luminal air, abdominal fat, abdominal soft tissue, and tagged fecal material, respectively. Conclusions: In our study, we observed that the DEI values of colonic luminal air in DE-CTC images (>0.10) were substantially higher than the theoretical value of 0.0063. In addition, the observed DEI values of colonic luminal air were significantly higher than those of soft tissue. These findings have an important impact on electronic cleansing: it may provide an effective means of differentiating colonic soft-tissue structures from the air-tagging mixture caused by the partial volume effect and thus of minimizing the cleansing artifacts. C1 [Cai, Wenli; Zhang, Da; Lee, June-Goo; Shirai, Yu; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; Zhang, Da; Lee, June-Goo; Shirai, Yu; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Se Hyung] Seoul Natl Univ Hosp, Coll Med, Dept Radiol, Seoul 110744, South Korea. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA. EM Cai.Wenli@mgh.harvard.edu FU American Cancer Society [RSG-11-076-01-CCE]; National Cancer Institute [R01CA095279, R01CA131718] FX The project described was partly supported by research scholar grant RSG-11-076-01-CCE from the American Cancer Society and by grants R01CA095279 and R01CA131718 from National Cancer Institute. NR 28 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2013 VL 37 IS 2 BP 183 EP 194 DI 10.1097/RCT.0b013e31827bc266 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109AO UT WOS:000316337700010 PM 23493207 ER PT J AU Moreno, CC Pinho, D Nelson, RC Sahani, DV Jenkins, M Zabrycki, M Chaudhry, H Kang, J Chen, ZJ AF Moreno, Courtney Coursey Pinho, Daniella Nelson, Rendon C. Sahani, Dushyant V. Jenkins, Melissa Zabrycki, MaryAnne Chaudhry, Humaira Kang, Jian Chen, Zhengjia TI Lessons Learned from 118,970 Multidetector Computed Tomographic Intravenous Contrast Material Administrations: Impact of Catheter Dwell Time and Gauge, Catheter Location, Rate of Contrast Material Administration, and Patient Age and Sex on Volume of Extravasate SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE extravasation; contrast material; computed tomography ID INJECTION; MEDIA; CT; MANAGEMENT; ULCERATION; FREQUENCY AB Objectives: The aim of this study was to determine the impact of catheter dwell time and gauge, catheter location, rate of contrast material administration, and patient age and sex on volume of extravasate at intravenous contrast-enhanced multidetector computed tomography. Methods: Incident reports were reviewed for all extravasation events that occurred in adult patients between March 2006 and December 2009 at 2 institutions. Patient age and sex; catheter dwell time, gauge, and location; rate of contrast material administration; and estimated volume of extravasated contrast material were recorded. Results: Three hundred thirty extravasation events were recorded for the 118,970 contrast material administrations (0.3%). Mean volume of extravasated contrast material was statistically significantly less for catheters newly placed in the radiology department, for higher flow rates, for smaller gauge catheters, and for catheters placed in the hand. Mean volume of extravasated contrast material did not vary significantly based on patient age or sex. Conclusions: The volume of extravasate was likely to be smaller for smaller-gauge catheters in the hand with higher flow rates and for catheters newly placed in the radiology department. C1 [Moreno, Courtney Coursey; Kang, Jian] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. [Pinho, Daniella; Sahani, Dushyant V.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Nelson, Rendon C.; Jenkins, Melissa; Zabrycki, MaryAnne] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chaudhry, Humaira] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Chen, Zhengjia] Emory Univ, Sch Med, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. RP Moreno, CC (reprint author), Emory Univ, Sch Med, Dept Radiol & Imaging Sci, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM courtney.coursey@emoryhealthcare.org FU Becton, Dickinson and Company (Franklin Lakes, NJ) [07417] FX Support for this research was provided by Becton, Dickinson and Company (Franklin Lakes, NJ 07417). NR 13 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2013 VL 37 IS 2 BP 286 EP 288 DI 10.1097/RCT.0b013e31828211da PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109AO UT WOS:000316337700024 PM 23493221 ER PT J AU Christophi, CA Resnick, HE Ratner, RE Temprosa, M Fowler, S Knowler, WC Shamoon, H Barrett-Connor, E Kahn, SE AF Christophi, C. A. Resnick, H. E. Ratner, R. E. Temprosa, M. Fowler, S. Knowler, W. C. Shamoon, H. Barrett-Connor, E. Kahn, S. E. CA Diabet Prevention Program Res Grp TI Confirming Glycemic Status in the Diabetes Prevention Program: Implications for Diagnosing Diabetes in High Risk Adults SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetes mellitus; Screening; Epidemiology ID IMPAIRED GLUCOSE-TOLERANCE; NUTRITION EXAMINATION SURVEY; CAUCASIAN POPULATION; FASTING GLUCOSE; PREVALENCE; HEALTH; HOORN AB Aims: To examine the ability of fasting plasma glucose (FPG) and/or 2-h glucose to confirm diabetes and to determine the proportion of participants with HbA1c >= 6.5%. Methods: Diabetes confirmation rates were calculated after a single elevated FPG and/or 2-h glucose on an oral glucose tolerance test (OGTT) using a confirmatory OGTT performed within 6 weeks. Results: 772 (24%) participants had elevated FPG or 2-h glucose on an OGTT that triggered a confirmation visit. There were 101 triggers on FPG alone, 574 on 2-h glucose alone, and 97 on both. Only 47% of participants who triggered had confirmed diabetes. While the confirmation rate for FPG was higher than that for 2-h glucose, the larger number of 2-h glucose triggers resulted in 87% of confirmed cases triggering on 2-h glucose. Confirmation rates increased to 75% among persons with FPG >= 126 mg/dl and HbA1c >= 6.5%. Conclusions: Only half of the persons with elevated FPG and IGT were subsequently confirmed to have diabetes. At current diagnostic levels, more persons trigger on 2-h glucose than on FPG, but fewer of these persons have their diagnoses confirmed. In individuals with FPG >= 126 mg/dl and HbA1c >= 6.5%, the confirmation rate was increased. (C) 2013 Elsevier Inc. All rights reserved. C1 [Christophi, C. A.; Temprosa, M.; Fowler, S.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Resnick, H. E.] Amer Assoc Homes & Serv Aging, Inst Future Aging Serv, Washington, DC USA. [Resnick, H. E.] Georgetown Univ, Washington, DC USA. [Ratner, R. E.] MedStar Res Inst, Hyattsville, MD USA. [Knowler, W. C.] NIDDKD, Phoenix, AZ USA. [Shamoon, H.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Barrett-Connor, E.] Univ Calif San Diego, San Diego, CA 92103 USA. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. RP Christophi, CA (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. EM dppmail@bsc.gwu.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; Uwaifo, Gabriel/M-2361-2016; OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Uwaifo, Gabriel/0000-0002-6962-9304; Shamoon, Harry/0000-0002-5014-5211; Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; 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; Department of Veterans Affairs; American Diabetes Association; intramural research program of the NIDDK; McKesson BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson Foundation; Coordinating Center 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 centers and the Coordinating Center for the design and conduct of the study; collection, management, analysis, and interpretation of the data. 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 and Department of Veteran Affairs supported data collection at many of the clinical centers. 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 Department of Veterans Affairs and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. 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 Center. 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 Centers, investigators, and staff can be found in Appendix 1. NR 20 TC 5 Z9 5 U1 0 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR-APR PY 2013 VL 27 IS 2 BP 150 EP 157 DI 10.1016/j.jdiacomp.2012.09.012 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109NG UT WOS:000316374700008 PM 23140912 ER PT J AU Faulenbach, MV Wright, LA Lorenzo, C Utzschneider, KM Goedecke, JH Fujimoto, WY Boyko, EJ McNeely, MJ Leonetti, DL Haffner, SM Kahn, SE AF Faulenbach, Mirjam V. Wright, Lorena A. Lorenzo, Carlos Utzschneider, Kristina M. Goedecke, Julia H. Fujimoto, Wilfred Y. Boyko, Edward J. McNeely, Marguerite J. Leonetti, Donna L. Haffner, Steven M. Kahn, Steven E. CA Amer Diabet Assoc GENNID Study Grp TI Impact of differences in glucose tolerance on the prevalence of a negative insulinogenic index SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Oral glucose tolerance test; Glucose; Insulin; Insulinogenic index; Impaired glucose tolerance; Diabetes ID BETA-CELL FUNCTION; DIABETES-MELLITUS; MEXICAN-AMERICANS; HIGH-RISK; SECRETION; HYPERINSULINEMIA; SENSITIVITY; RESISTANCE; OBESITY; NIDDM AB Objective: To determine the prevalence of a negative insulinogenic index (change in plasma insulin/change in plasma glucose from 0 to 30 mm) from an oral glucose tolerance test according to glucose tolerance category. Materials and Methods: Data from the San Antonio Heart Study (n = 2494), Japanese American Community Diabetes Study (JACDS; n=594) and Genetics of NIDDM Study (n=1519) were examined. Glucose tolerance was defined by ADA criteria. Results: In the combined cohort, the prevalence of a negative insulinogenic index was significantly higher in diabetes 20/616 (3.2%) compared to normal glucose tolerance 43/2667 (1.6%) (p<0.05). Longitudinally, in the JACDS cohort, the prevalence did not change from baseline (3/594; 0.5%) to 5 (4/505; 0.7%) and 10 years (8/426; 1.9%) (p=0.9) and no subject had a repeat negative insulinogenic index. Conclusions: A negative insulinogenic index occurs at a low prevalence across glucose tolerance categories although more often in diabetes, but without recurrence over time. (C) 2013 Published by Elsevier Inc. C1 [Faulenbach, Mirjam V.; Wright, Lorena A.; Utzschneider, Kristina M.; Fujimoto, Wilfred Y.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Faulenbach, Mirjam V.; Wright, Lorena A.; Utzschneider, Kristina M.; Fujimoto, Wilfred Y.; Boyko, Edward J.; Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Lorenzo, Carlos; Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Goedecke, Julia H.; McNeely, Marguerite J.] Univ Cape Town, Dept Human Biol, South African Med Res Council, ZA-7700 Rondebosch, South Africa. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Dept Med, Div Gen Internal Med, Seattle, WA USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst 151, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Goedecke, Julia/J-8628-2013; Goedecke, Julia/E-1820-2016; OI Goedecke, Julia/0000-0001-6795-4771; Goedecke, Julia/0000-0001-6795-4771; Kahn, Steven/0000-0001-7307-9002 FU Department of Veterans Affairs; NIH in Seattle [DK-002654, DK-007247, DK-017047, DK-031170, DK-035816, HL-049293, RR-000037]; NIH in San Antonio [HL-24799, HL-36820]; American Diabetes Association; Swiss National Foundation [PBZHB-116877] FX We thank the study participants who made this analysis possible. The study was supported in part by the Department of Veterans Affairs, NIH grants, DK-002654, DK-007247, DK-017047, DK-031170, DK-035816, HL-049293 and RR-000037 in Seattle, HL-24799 and HL-36820 in San Antonio, and the American Diabetes Association. MVF was supported by the Swiss National Foundation grant PBZHB-116877. NR 15 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR-APR PY 2013 VL 27 IS 2 BP 158 EP 161 DI 10.1016/j.jdiacomp.2012.09.011 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109NG UT WOS:000316374700009 PM 23140910 ER PT J AU Maison, SF Pyott, SJ Meredith, AL Liberman, MC AF Maison, Stephane F. Pyott, Sonja J. Meredith, Andrea L. Liberman, M. Charles TI Olivocochlear suppression of outer hair cells in vivo: evidence for combined action of BK and SK2 channels throughout the cochlea SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE inner ear; efferent feedback; calcium-activated channels; cholinergic ID ACTIVATED POTASSIUM CHANNELS; CA2+-ACTIVATED K+ CHANNEL; ACOUSTIC INJURY; CHOLINERGIC INHIBITION; MOUSE COCHLEA; ALPHA-SUBUNIT; HEARING-LOSS; CALCIUM; IDENTIFICATION; LOCALIZATION AB Maison SF, Pyott SJ, Meredith AL, Liberman MC. Olivocochlear suppression of outer hair cells in vivo: evidence for combined action of BK and SK2 channels throughout the cochlea. J Neurophysiol 109: 1525-1534, 2013. First published January 2, 2013; doi: 10.1152/jn.00924.2012.-Cholinergic inhibition of cochlear hair cells via olivocochlear (OC)-efferent feedback is mediated by Ca2+ entry through alpha(9)-/alpha(10)-nicotinic receptors, but the nature of the K+ channels activated by this Ca2+ entry has been debated (Yoshida N, Hequembourg SJ, Atencio CA, Rosowski JJ, Liberman MC. J Neurophysiol 85: 84-88, 2001). A recent in vitro study (Wersinger E, McLean WJ, Fuchs PA, Pyott SJ. PLoS One 5: e13836, 2010) suggests that small-conductance (SK2) channels mediate cholinergic effects in the apical turn, whereas large-conductance (BK) channels mediate basal turn effects. Here, we measure, as a function of cochlear frequency, the magnitude of BK and SK2 expression in outer hair cells and the strength of in vivo OC suppression in BK+/+ mice vs. BK-/- lacking the obligatory alpha-subunit (Meredith AL, Thorneloe KS, Werner ME, Nelson MT, Aldrich RW. J Biol Chem 279: 3674636752, 2004). Except at the extreme apical tip, we see immunostaining for both BK and SK2 in BK+/+. Correspondingly, at all testable frequencies (8-45 kHz), we see evidence for both SK2 and BK contributions to OC effects evoked by electrically stimulating the OC bundle: OC-mediated suppression was reduced, but not eliminated, at all frequencies in the BK-/- ears. The suppression remaining in BK nulls was blocked by strychnine, suggesting involvement of alpha(9)-/alpha(10) cholinergic receptors, coupled to activation of the remaining SK2 channels. C1 [Maison, Stephane F.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Maison, Stephane F.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Maison, Stephane F.; Liberman, M. Charles] Harvard Program Speech & Hearing Biosci & Technol, Boston, MA USA. [Pyott, Sonja J.] Univ N Carolina, Dept Biol & Marine Biol, Wilmington, NC 28401 USA. [Meredith, Andrea L.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM stephane_maison@meei.harvard.edu FU Hearing Health Foundation; National Institutes of Health [R01-DC-0188, P30-DC-5029, R01-HL-102758] FX This work was supported by grants from the Hearing Health Foundation (S. J. Pyott) and the National Institutes of Health Grants R01-DC-0188 (M. C. Liberman), P30-DC-5029 (M. C. Liberman), and R01-HL-102758 (A. L. Meredith). NR 37 TC 12 Z9 12 U1 0 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2013 VL 109 IS 6 BP 1525 EP 1534 DI 10.1152/jn.00924.2012 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 107HC UT WOS:000316205100006 PM 23282326 ER PT J AU Abramowicz, S Kim, S Susarla, HK Kaban, LB AF Abramowicz, Shelly Kim, Susan Susarla, Harlyn K. Kaban, Leonard B. TI Differentiating Arthritic From Myofascial Pain in Children With Juvenile Idiopathic Arthritis: Preliminary Report SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons (AAOMS) Held in Conjunction with the Scandinavian-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 12-17, 2011 CL Philadelphia, PA SP Amer Assoc Oral & Maxillofacial Surg (AAOMS), Scandinavian Assoc Oral & Maxillofacial Surg ID TEMPOROMANDIBULAR-JOINT ARTHRITIS; MAGNETIC-RESONANCE; INVOLVEMENT; PREVALENCE; ULTRASOUND AB Purpose: To differentiate between temporomandibular joint (TMJ) inflammation and myofascial pain (MPD) in children with juvenile idiopathic arthritis (JIA). Patients and Methods: We performed a retrospective study of children with JIA evaluated at Boston Children's Hospital, Boston, Massachusetts. Patients, aged 16 years or younger at the time of diagnosis, were included if they had confirmed JIA with jaw signs or symptoms. Medical records and imaging studies were reviewed to document demographic, clinical, and radiographic findings. Patients with clinical evidence (joint pain/tenderness, asymmetry, limited motion) and radiographic evidence (condylar asymmetry, flattening, accentuated antegonial notch) of TMJ inflammation but without muscle pain were diagnosed with arthritis. Those with only muscle tenderness and/or limited jaw motion were diagnosed with MPD. Patients with TMJ inflammation and muscle pain/tenderness were considered to have coexisting arthritis and MPD. Outcome variables were the presence of TMJ arthritis and/or MPD. Descriptive statistics were computed. Results: There were 61 patients (44 girls) with a mean age of 12.7 years (range, 3 to 16 years) who met the inclusion criteria. The most common clinical findings were limited mouth opening (n = 24), malocclusion/asymmetry (n = 23), and/or tenderness to palpation (n = 18). Twenty-one patients had multiple signs and symptoms. Panoramic radiographs showed condylar abnormalities in 32 patients. Overall, 21 patients (34.4%) were diagnosed with active TMJ arthritis, 21 (34.4%) with MPD, and 11 (18%) with both arthritis and MPD. Of the patients, 8 (13.1%) were in remission. Conclusions: The results of this study indicate that in patients with JIA and jaw signs/symptoms, there is an overlap in diagnoses between arthritis and MPD. This has considerable implications for patient management. (C) 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71:493-496, 2013 C1 [Abramowicz, Shelly; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Abramowicz, Shelly] Boston Childrens Hosp, Boston, MA 02445 USA. [Kim, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Susan] Boston Childrens Hosp, Rheumatol Program, Boston, MA 02445 USA. [Susarla, Harlyn K.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Kaban, Leonard B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Abramowicz, S (reprint author), Boston Childrens Hosp, Dept Plast & Oral Surg, 300 Longwood Ave, Boston, MA 02445 USA. EM shelly.abramowicz@childrens.harvard.edu NR 21 TC 8 Z9 8 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2013 VL 71 IS 3 BP 493 EP 496 DI 10.1016/j.joms.2012.10.027 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 107YM UT WOS:000316256900008 PM 23298802 ER PT J AU Chae, Y Chang, DS Lee, SH Jung, WM Lee, IS Jackson, S Kong, J Lee, H Park, HJ Lee, H Wallraven, C AF Chae, Younbyoung Chang, Dong-Seon Lee, Soon-Ho Jung, Won-Mo Lee, In-Seon Jackson, Stephen Kong, Jian Lee, Hyangsook Park, Hi-Joon Lee, Hyejung Wallraven, Christian TI Inserting Needles Into the Body: A Meta-Analysis of Brain Activity Associated With Acupuncture Needle Stimulation SO JOURNAL OF PAIN LA English DT Review DE Acupuncture; analgesia; functional magnetic resonance imaging (fMRI); meta-analysis; pain ID ELECTROACUPUNCTURE STIMULATION; IMPLICATED ACUPOINTS; NEURONAL SPECIFICITY; CORTICAL ACTIVATIONS; ALTERNATIVE MEDICINE; DEFAULT MODE; FMRI; PAIN; POINT; MECHANISMS AB Acupuncture is a therapeutic treatment that is defined as the insertion of needles into the body at specific points (ie, acupoints). Advances in functional neuroimaging have made it possible to study brain responses to acupuncture; however, previous studies have mainly concentrated on acupoint specificity. We wanted to focus on the functional brain responses that occur because of needle insertion into the body. An activation likelihood estimation meta-analysis was carried out to investigate common characteristics of brain responses to acupuncture needle stimulation compared to tactile stimulation. A total of 28 functional magnetic resonance imaging studies, which consisted of 51 acupuncture and 10 tactile stimulation experiments, were selected for the meta-analysis. Following acupuncture needle stimulation, activation in the sensorimotor cortical network, including the insula, thalamus, anterior cingulate cortex, and primary and secondary somatosensory cortices, and deactivation in the limbic-paralimbic neocortical network, including the medial prefrontal cortex, caudate, amygdala, posterior cingulate cortex, and parahippocampus, were detected and assessed. Following control tactile stimulation, weaker patterns of brain responses were detected in areas similar to those stated above. The activation and deactivation patterns following acupuncture stimulation suggest that the hemodynamic responses in the brain simultaneously reflect the sensory, cognitive, and affective dimensions of pain. Perspective: This article facilitates a better understanding of acupuncture needle stimulation and its effects on specific activity changes in different brain regions as well as its relationship to the multiple dimensions of pain. Future studies can build on this meta-analysis and will help to elucidate the clinically relevant therapeutic effects of acupuncture. (C) 2013 by the American Pain Society. Published by Elsevier Inc. All rights reserved C1 [Chae, Younbyoung; Chang, Dong-Seon; Lee, Soon-Ho; Lee, In-Seon; Lee, Hyangsook; Park, Hi-Joon; Lee, Hyejung] Kyung Hee Univ, Acupuncture & Meridian Sci Res Ctr, Seoul 130701, South Korea. [Chae, Younbyoung; Jung, Won-Mo; Jackson, Stephen; Wallraven, Christian] Korea Univ, Dept Brain Cognit Engn, Seoul, South Korea. [Chang, Dong-Seon] Univ Tubingen, Int Max Planck Res Sch, Grad Sch Neural & Behav Sci, Tubingen, Germany. [Jackson, Stephen] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England. [Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Chae, Y (reprint author), Kyung Hee Univ, Acupuncture & Meridian Sci Res Ctr, 1 Hoegi Dong, Seoul 130701, South Korea. EM ybchae@khu.ac.kr RI Jackson, Stephen/B-1233-2009; OI Jackson, Stephen/0000-0002-5676-4072; Chang, Dong-Seon/0000-0003-4562-1321; LEE, HYANGSOOK/0000-0002-1107-9389 FU Basic Science Research Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2011-0009913, 2005-0049404] FX Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0009913 and No. 2005-0049404). NR 64 TC 43 Z9 45 U1 6 U2 46 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD MAR PY 2013 VL 14 IS 3 BP 215 EP 222 DI 10.1016/j.jpain.2012.11.011 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 105AO UT WOS:000316038200001 PM 23395475 ER PT J AU Traeger, L Cannon, S Pirl, WF Park, ER AF Traeger, Lara Cannon, Sheila Pirl, William F. Park, Elyse R. TI Depression and Undertreatment of Depression: Potential Risks and Outcomes in Black Patients with Lung Cancer SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE lung cancer; health disparities; depression; mental health care; psychosocial services ID MENTAL-HEALTH-SERVICES; NATIONAL COMORBIDITY SURVEY; PRIMARY-CARE PATIENTS; AFRICAN-AMERICAN; UNITED-STATES; RACIAL DISPARITIES; ETHNIC DISPARITIES; CULTURAL-DIFFERENCES; MINORITY-GROUPS; WHITE PATIENTS AB In the United States, Black men are at higher risk than White men for lung cancer mortality whereas rates are comparable between Black and White women. This article draws from empirical work in lung cancer, mental health, and health disparities to highlight that race and depression may overlap in predicting lower treatment access and utilization and poorer quality of life among patients. Racial barriers to depression identification and treatment in the general population may compound these risks. Prospective data are needed to examine whether depression plays a role in racial disparities in lung cancer outcomes. C1 [Traeger, Lara; Pirl, William F.; Park, Elyse R.] Massachusetts Gen Hosp, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Cannon, Sheila] Massachusetts Gen Hosp, Coll Nursing & Hlth Sci, Boston, MA 02114 USA. [Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Traeger, L (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ltraeger@partners.org FU NCI NIH HHS [U54 CA156732, 1U54 CA156732] NR 82 TC 3 Z9 3 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PD MAR 1 PY 2013 VL 31 IS 2 BP 123 EP 135 DI 10.1080/07347332.2012.761320 PG 13 WC Psychology, Social SC Psychology GA 108YA UT WOS:000316331100001 PM 23514250 ER PT J AU Delahanty, L Kriska, A Edelstein, S Amodei, N Chadwick, J Copeland, K Galvin, B El Ghormli, L Haymond, M Kelsey, MM Lassiter, C Milaszewski, K Syme, A Mayer-Davis, E AF Delahanty, Linda Kriska, Andrea Edelstein, Sharon Amodei, Nancy Chadwick, Jennifer Copeland, Kenneth Galvin, Bryan El Ghormli, Laure Haymond, Morey Kelsey, Megan M. Lassiter, Chad Milaszewski, Kerry Syme, Amy Mayer-Davis, Elizabeth TI Self-Reported Dietary Intake of Youth with Recent Onset of Type 2 Diabetes: Results from the TODAY Study SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Food/nutrient intake; Diet intake assessment; Type 2 diabetes; Adolescence; Obesity/overweight ID BASE-LINE; CARDIOVASCULAR RISK; NATIONAL-HEALTH; ADOLESCENTS; CHILDREN; SEARCH; CONSUMPTION; MELLITUS; VALIDITY; PROGRAM AB Despite the widely recognized importance of diet in managing diabetes, few studies have documented usual dietary intake in young people with type 2 diabetes. The objectives of our study were to assess dietary intake among a large, ethnically diverse cohort of young people with type 2 diabetes and compare intake to current recommendations. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is a multicenter randomized clinical trial of 699 youth aged 10 to 17 years. At baseline, following a run-in period that included standard diabetes education, diet was assessed using a food frequency questionnaire between 2004 and 2009. Analysis of variance and nonparametric tests were used to compare mean and median nutrient intakes; logistic regression was used to compare the odds of meeting predefined dietary intake recommendation cutpoints between subgroups of age, sex, and race-ethnicity. Percent of energy from saturated fat was consistently 13% to 14% across all subgroups substantially exceeding national recommendations. Overall, only 12% of youth met Healthy People 2010 guidelines for intake of <10% of energy from saturated fat and only 1% of youth met American Diabetes Association recommendations for intake of <7% of energy from saturated fat. Dietary intake fell substantially below other Healthy People 2010 targets; only 3% met calcium intake goals, 11% met fruit consumption goals, 5% met vegetable consumption goals, and 67% met grain intake goals. Overall, dietary intake in this large cohort of young people with type 2 diabetes fell substantially short of recommendations, in ways that were consistent by sex, age, and race-ethnicity. The data suggest a critical need for better approaches to improve dietary intake of these young people. J Acad Nutr Diet. 2013;113:431-439. C1 [Delahanty, Linda] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delahanty, Linda] Harvard Univ, Sch Med, Boston, MA USA. [Kriska, Andrea] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Edelstein, Sharon; El Ghormli, Laure] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Amodei, Nancy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX USA. [Chadwick, Jennifer] Univ Oklahoma, Childrens Diabet Ctr, Native Amer Program, Oklahoma City, OK USA. [Copeland, Kenneth] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA. [Galvin, Bryan] Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Pittsburgh, PA USA. [Haymond, Morey] Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Kelsey, Megan M.] Childrens Hosp Colorado, Aurora, CO USA. [Lassiter, Chad] Univ Penn, Black Men Penn, Philadelphia, PA 19104 USA. [Lassiter, Chad] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Milaszewski, Kerry] Joslin Diabet Ctr, Boston, MA 02215 USA. [Syme, Amy] Yale Univ, Dept Pediat Endocrinol, New Haven, CT USA. [Mayer-Davis, Elizabeth] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. RP El Ghormli, L (reprint author), George Washington Univ, Ctr Biostat, 6110 Execut Blvd,Ste 750, Rockville, MD 20852 USA. EM elghorml@biostat.bsc.gwu.edu OI Kriska, Andrea/0000-0002-3522-0869 FU Daichii Sankyo; Bristol-Myers Squibb; Merck; National Institute of Diabetes and Digestive and Kidney Disease/National Institutes of Health [U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254]; National Center for Research Resources General Clinical Research Centers Program [M01-RR00036, M01-RR00043-45, M01-RR00069, M01-RR00084, M01-RR01066, M01-RR00125, M01-RR14467]; National Center for Research Resources Clinical and Translational Science Awards [UL1-RR024134, UL1-RR024139, UL1-RR024153, UL1-RR024989, UL1-RR024992, UL1-RR025758, UL1-RR025780]; Becton, Dickinson and Company; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc; Pfizer; Sanofi-Aventis FX Dr Copeland is on the National Advisory Committee and a consultant with Honoraria to Novo Nordisk and Daiichi Sankyo Inc; Dr Kelsey is an investigator for type 2 diabetes sponsored by Daichii Sankyo; Bristol-Myers Squibb,and Merck; Ms Milaszewski is a consultant for Medtronic insulin pumps; the other authors have indicated they have no financial relationships relevant to this article to disclose.; This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Disease/National Institutes of Health grant nos. U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254; from the National Center for Research Resources General Clinical Research Centers Program grant nos, M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (childrens Hospital Los Angeles), M01-RR00069 (University of Colorado Denver), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and from the National Center for Research Resources Clinical and Translational Science Awards grant nos.UL1-RR024134 (Children's Hospital of Philadelphia), UL1-RR024139 (Yale University), UL1-RR024153 (Children's Hospital of Pittsburgh), UL1-RR024989 (Case Western Reserve University), UL1-RR024992 (Washington University), UL1-RR025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver). The TODAY Study Group thanks the following companies for donations in support of the study's efforts: Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc; Pfizer; and Sanofi-Aventis. The authors alto thank the American Indian partners associated with the clinical center located at the University of Oklahoma Health Sciences Center, including members of the Absentee Shawnee Tribe, Cherokee Nation, Chickasaw Nation, Choctaw Nation of Oklahoma, and Oklahoma City Area Indian Health Service. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the respective Tribal and Indian Health Service Institution Review Boards or their members. NR 29 TC 4 Z9 4 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD MAR PY 2013 VL 113 IS 3 BP 431 EP 439 DI 10.1016/j.jand.2012.11.015 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 102JU UT WOS:000315841700008 PM 23438494 ER PT J AU Jones, BA Hull, MA Potanos, KM Zurakowski, D Fitzgibbons, SC Ching, YA Duggan, C Jaksic, T Kim, HB AF Jones, Brian A. Hull, Melissa A. Potanos, Kristina M. Zurakowski, David Fitzgibbons, Shimae C. Ching, Y. Avery Duggan, Christopher Jaksic, Tom Kim, Heung Bae CA Int STEP Data Registry TI Report of 111 Consecutive Patients Enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: A Retrospective Observational Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SHORT-BOWEL SYNDROME; OUTCOMES; CHILDREN; MODEL AB BACKGROUND: The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors that are significantly associated with transplantation or death or attainment of enteral autonomy after STEP. STUDY DESIGN: Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine the predictors of transplantation or death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. RESULTS: Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = 0.05 and p < 0.001, respectively). Of the 78 patients who were 7 days of age or older and required parenteral nutrition at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = 0.002). Median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI, 12-30). CONCLUSIONS: Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy. (J Am Coll Surg 2013;216:438-446. (C) 2013 by the American College of Surgeons) C1 [Jones, Brian A.] Univ Texas Med Sch Houston, Dept Pediat Surg, Houston, TX USA. [Hull, Melissa A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Potanos, Kristina M.; Zurakowski, David; Jaksic, Tom; Kim, Heung Bae] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Potanos, Kristina M.; Kim, Heung Bae] Boston Childrens Hosp, Pediat Transplant Ctr, Boston, MA USA. [Duggan, Christopher; Jaksic, Tom; Kim, Heung Bae] Boston Childrens Hosp, Ctr Adv Intestinal Rehabil, Boston, MA USA. [Duggan, Christopher] Boston Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Fitzgibbons, Shimae C.] Lahey Clin Med Ctr, Dept Surg, Burlington, MA 01803 USA. [Ching, Y. Avery] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. RP Kim, HB (reprint author), Pediat Transplant Ctr, Dept Surg, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. EM heung.kim@childrens.harvard.edu FU NICHD NIH HHS [K24 HD058795] NR 16 TC 29 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2013 VL 216 IS 3 BP 438 EP 446 DI 10.1016/j.jamcollsurg.2012.12.018 PG 9 WC Surgery SC Surgery GA 109GH UT WOS:000316353900013 PM 23357726 ER PT J AU Zhu, CW Sano, M Ferris, SH Whitehouse, PJ Patterson, MB Aisen, PS AF Zhu, Carolyn W. Sano, Mary Ferris, Steven H. Whitehouse, Peter J. Patterson, Marian B. Aisen, Paul S. TI Health-Related Resource Use and Costs in Elderly Adults with and without Mild Cognitive Impairment SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mild cognitive impairment; casecontrol study; medical care; resource use; cost; informal care ID ALZHEIMERS-DISEASE; CLINICAL-TRIALS; CARE UTILIZATION; RATING-SCALE; SELF-REPORTS; DEMENTIA AB Objectives To assess differences in resource use and cost between older adults with and without mild cognitive impairment (MCI) over time. Design Multicenter, longitudinal study. Setting Sixty-eight Alzheimer's Disease Cooperative Study (ADCS) sites in the United States. Participants Two hundred fifty-nine individuals diagnosed with MCI and 107 cognitively normal elderly adults followed annually for 3years. Measurements The Resource Use Instrument (RUI) was used to capture medical and nonmedical care use. Generalized linear latent and mixed models were used to estimate differences in resource use and costs in older adults with and without MCI after controlling for clinical and demographic characteristics. Results At baseline, average annual direct medical cost per person was substantially higher for participants with MCI ($6,499) than for those without ($2,969) P<.001). Informal care use was also substantially higher (33% vs 8.4%, P<.001). Results from multivariate analyses of longitudinal data show that, after controlling for participant and informant characteristics, direct medical costs were 44% higher for participants with MCI than for those without. Participants with MCI were almost five times as likely to use informal care as those without. Number of medical conditions and older age were associated with higher medical cost. Worse functional and cognitive status, older age, being married, and being female were associated with higher likelihood of informal care use. Having an adult child informant was associated with higher likelihood of using informal care. Conclusion The RUI captured differences in resource use and costs between individuals with and without MCI. Clinicians who care for individuals with MCI should address informal care needs early in the disease course. C1 [Zhu, Carolyn W.] Alzheimer Dis Res Ctr, Dept Geriatr & Palliat Med, Bronx, NY USA. [Sano, Mary] Alzheimer Dis Res Ctr, Mt Sinai Sch Med, Dept Psychiat, Bronx, NY USA. [Sano, Mary] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Ferris, Steven H.] NYU, Langone Med Ctr, Alzheimers Dis Ctr, New York, NY USA. [Whitehouse, Peter J.; Patterson, Marian B.] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. RP Zhu, CW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM carolyn.zhu@mssm.edu OI Ferris, Steven/0000-0001-8641-6223 FU National Institute on Aging [U01AG10483]; National Institute on Aging (NIA), National Center for Research Resources, National Institutes of Health (NIH); Baxter; Bristol Myers Squibb; Janssen Alzheimer Immunotherapy; Eisai; Eli Lilly; Medivation; Pfizer; NIA, NIH; Pfizer Inc.; Baxter International Inc.; NIH [NIA U01-AG10483, NIA U01-AG024904, NIA R01-AG030048, R01-AG16381] FX The work was supported by National Institute on Aging Grant U01AG10483. Dr. Sano serves on a scientific advisory board for Medivation, Inc. and as a consultant for Bayer Schering Pharma, Bristol-Meyers Squibb, Elan Corporation, Genentech, Inc., Medivation, Inc., Medpace Inc., Pfizer Inc, Janssen, Takeda Pharmaceutical Company Limited, and United Biosource Corporation and receives research support from the National Institute on Aging (NIA), National Center for Research Resources, National Institutes of Health (NIH).; Dr. Ferris serves as a consultant or advisory board member for Accera, Baxter, Bristol Myers Squibb, Eisai, Intellect Neurosciences, Janssen Alzheimer Immunotherapy, Elan, Eli Lilly, MedAvante, Merck, Merz, Neuronix, Pfizer, and United Biosource and receives research support from Baxter, Bristol Myers Squibb, Janssen Alzheimer Immunotherapy, Eisai, Eli Lilly, Medivation, Pfizer, and the NIA, NIH.; D. Aisen serves on a scientific advisory board for NeuroPhage and as a consultant to Elan Corporation, Wyeth, Eisai Inc., Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck & Co., Roche, Amgen, Abbott, Pfizer Inc, Novartis, Bayer, Astellas, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, AstraZeneca, Janssen, Medivation, Inc., Theravance, Cardeus, and Anavex and receives research support from Pfizer Inc., Baxter International Inc., and the NIH (NIA U01-AG10483 (PI), NIA U01-AG024904 (Coordinating Center Director), NIA R01-AG030048 (PI), and R01-AG16381 (Co-I)). NR 29 TC 14 Z9 14 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2013 VL 61 IS 3 BP 396 EP 402 DI 10.1111/jgs.12132 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 108ZM UT WOS:000316334900011 PM 23414481 ER PT J AU Buehring, B Hind, J Fidler, E Krueger, D Binkley, N Robbins, J AF Buehring, Bjoern Hind, Jacqueline Fidler, Ellen Krueger, Diane Binkley, Neil Robbins, JoAnne TI Tongue Strength Is Associated with Jumping Mechanography Performance and Handgrip Strength but Not with Classic Functional Tests in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sarcopenia; swallowing; jumping mechanography; muscle function; tongue strength ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; LINGUAL EXERCISE; HIP FRACTURE; MUSCLE MASS; SARCOPENIA; AGE; DISABILITY; POWER; HOSPITALIZATION AB Objectives To determine whether classic muscle function tests and jumping mechanography (JM) are related to tongue strength. Design Cross-sectional. Setting Community. Participants Ninety-seven community-dwelling individuals aged 70 and older (49 female, 48 male, mean age 80.7, range 7095) with and without identified sarcopenia. Measurements Participants performed muscle function tests including the Short Physical Performance Battery (SPPB), grip strength, and JM. Isometric tongue strength was evaluated using the Iowa Oral Performance Instrument (IOPI). JM consisted of maximal countermovement jumps performed on a force plate to calculate weight-corrected peak power and jump height. Total body dual-energy X-ray absorptiometry was used to assess appendicular lean mass (ALM) to define sarcopenia based on commonly used ALM/height2 cutoffs. Associations between IOPI measures and other muscle function tests were evaluated. Results Sarcopenia was present in 23.7% (23/97) of this cohort. Anterior isometric tongue pressure was positively correlated with grip strength (P=.003), jump height (P=.01), and power (P=.04). Individuals in the lowest tertile of tongue pressure had lower scores on these muscle function tests than individuals in the other tertiles. Classic functional tests and ALM/height2 were unrelated to tongue strength. Conclusion In older adults with and without sarcopenia, isometric tongue pressure is positively correlated with grip strength and jump height and power. These data support consideration of oropharyngeal functional decline as part of the sarcopenia syndrome. C1 [Buehring, Bjoern; Fidler, Ellen; Krueger, Diane; Binkley, Neil] Univ Wisconsin, Osteoporosis Clin Res Program, Madison, WI 53705 USA. [Buehring, Bjoern; Hind, Jacqueline; Binkley, Neil; Robbins, JoAnne] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Buehring, Bjoern; Hind, Jacqueline; Binkley, Neil; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. RP Buehring, B (reprint author), Univ Wisconsin, Osteoporosis Clin Res Program, 2870 Univ Ave,Suite 100, Madison, WI 53705 USA. EM bbuehring@medicine.wisc.edu RI Buehring, Bjoern/L-5581-2013 OI Buehring, Bjoern/0000-0003-3841-624X FU Merck Co., Inc. FX Sponsored by an investigator initiated research grant from Merck & Co., Inc. Jacqueline Hind was a consultant for Swallow Solutions, LLC, during data collection and analysis for this manuscript. Dr. Binkley is participating in a multicenter trial with Lilly in functional outcomes in older adults. He also consults on the same project. Dr. Robbins serves as the Chief Clinical Research Officer for Swallow Solutions, LLC. All other authors have no conflicts of interest. NR 29 TC 16 Z9 16 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2013 VL 61 IS 3 BP 418 EP 422 DI 10.1111/jgs.12124 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 108ZM UT WOS:000316334900015 PM 23379330 ER PT J AU Neuman, MD Ibrahim, SA Barg, FA Osigwe, C Karlawish, JH AF Neuman, Mark D. Ibrahim, Said A. Barg, Frances A. Osigwe, Chidimma Karlawish, Jason H. TI Race and Patient Preferences for Hip Fracture Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Neuman, Mark D.] Univ Penn, Leonard Davis Inst Hlth Econ, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.; Karlawish, Jason H.] Univ Penn, Leonard Davis Inst Hlth Econ, Dept Med, Philadelphia, PA 19104 USA. [Barg, Frances A.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Osigwe, Chidimma] Louisiana State Univ, Sch Med, New Orleans, LA USA. RP Neuman, MD (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. FU NIA NIH HHS [P30AG031043] NR 10 TC 1 Z9 1 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2013 VL 61 IS 3 BP 468 EP 470 DI 10.1111/jgs.12082 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 108ZM UT WOS:000316334900031 PM 23496189 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Keeping Cancer Patients Out of the Hospital at the End of Life SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID OF-LIFE; CARE; HEALTH; PLACE; DEATH C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] Dana Farber, Boston, MA USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2013 VL 11 IS 3 BP 229 EP 230 PG 2 WC Oncology SC Oncology GA 105AG UT WOS:000316037400001 PM 23486448 ER PT J AU Roeland, E Loprinzi, C Moynihan, TJ Smith, TJ Temel, J AF Roeland, Eric Loprinzi, Charles Moynihan, Timothy J. Smith, Thomas J. Temel, Jennifer TI In Chemotherapy for Lung Cancer, Sometimes Less is More SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID RETROSPECTIVE ANALYSIS; PERFORMANCE STATUS; PALLIATIVE CARE; SURVIVAL; LIFE; END; HOSPICE; AGGRESSIVENESS; CARBOPLATIN; DISCUSSIONS C1 [Roeland, Eric] UC San Diego Moores Canc Ctr, La Jolla, CA 92093 USA. [Loprinzi, Charles; Moynihan, Timothy J.] Mayo Clin, Rochester, MN USA. [Smith, Thomas J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Temel, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roeland, E (reprint author), UC San Diego Moores Canc Ctr, La Jolla, CA 92093 USA. NR 28 TC 5 Z9 5 U1 0 U2 5 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2013 VL 11 IS 3 BP 232 EP 235 PG 4 WC Oncology SC Oncology GA 105AG UT WOS:000316037400002 PM 23486449 ER PT J AU Zelenetz, AD Wierda, WG Abramson, JS Advani, RH Andreadis, CB Bartlett, N Bellam, N Byrd, JC Czuczman, MS Fayad, LE Glenn, MJ Gockerman, JP Gordon, LI Harris, NL Hoppe, RT Horwitz, SM Kelsey, CR Kim, YH Krivacic, S LaCasce, AS Nademanee, A Porcu, P Press, O Pro, B Reddy, N Sokol, L Swinnen, L Tsien, C Vose, JM Yahalom, J Zafar, N Dwyer, MA Naganuma, M AF Zelenetz, Andrew D. Wierda, William G. Abramson, Jeremy S. Advani, Ranjana H. Andreadis, C. Babis Bartlett, Nancy Bellam, Naresh Byrd, John C. Czuczman, Myron S. Fayad, Luis E. Glenn, Martha J. Gockerman, Jon P. Gordon, Leo I. Harris, Nancy Lee Hoppe, Richard T. Horwitz, Steven M. Kelsey, Christopher R. Kim, Youn H. Krivacic, Susan LaCasce, Ann S. Nademanee, Auayporn Porcu, Pierluigi Press, Oliver Pro, Barbara Reddy, Nishitha Sokol, Lubomir Swinnen, Lode Tsien, Christina Vose, Julie M. Yahalom, Joachim Zafar, Nadeem Dwyer, Mary A. Naganuma, Maoko TI Non-Hodgkin's Lymphomas, Version 1.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID HEPATITIS-B-VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; GENOTYPE 1 INFECTION; LENALIDOMIDE PLUS DEXAMETHASONE; STEM-CELL TRANSPLANTATION; NATURAL-KILLER-CELL; C-VIRUS; POSITIVE PATIENTS; CYTOTOXIC CHEMOTHERAPY; MALIGNANT-LYMPHOMA AB These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Non-Hodgkin's Lymphomas (NHL) and provide a discussion of the clinical evidence that support the updates. The updates discussed in this article feature recommendations for additional treatment options in patients with chronic lymphocytic leukemia and guidance surrounding the management Of hepatitis virus reactivation/infections in high-risk patients with NHL undergoing antitumor therapy. (JNCCN 2013;11:257-273) C1 [Zelenetz, Andrew D.; Horwitz, Steven M.; Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Wierda, William G.; Fayad, Luis E.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Abramson, Jeremy S.; Harris, Nancy Lee] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Advani, Ranjana H.; Hoppe, Richard T.; Kim, Youn H.] Stanford Canc Inst, Stanford, CA 94305 USA. [Andreadis, C. Babis] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA. [Bartlett, Nancy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Bartlett, Nancy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bellam, Naresh] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, W Midlands, England. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Byrd, John C.; Porcu, Pierluigi] Solove Res Inst, Columbus, OH USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Gockerman, Jon P.; Kelsey, Christopher R.] Duke Canc Inst, Durham, NC USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [LaCasce, Ann S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Nademanee, Auayporn] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Press, Oliver] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Pro, Barbara] Fox Chase Canc Ctr, Philadelphia, PA USA. [Reddy, Nishitha] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Swinnen, Lode] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Tsien, Christina] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Vose, Julie M.] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Zafar, Nadeem] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Dwyer, Mary A.; Naganuma, Maoko] Natl Comprehens Canc Network, Ft Washington, PA USA. RP Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. OI Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [P30 CA016672] NR 97 TC 23 Z9 29 U1 0 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2013 VL 11 IS 3 BP 257 EP 273 PG 17 WC Oncology SC Oncology GA 105AG UT WOS:000316037400005 PM 23486452 ER PT J AU Guinto, JB Szabatura, AH AF Guinto, Jake B. Szabatura, Audrea H. TI A Perspective on Dose Banding SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Guinto, Jake B.] Washington Univ, St Louis, MO USA. [Guinto, Jake B.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Guinto, Jake B.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Szabatura, Audrea H.] Dana Farber Canc Inst, Dept Pharm, Boston, MA 02115 USA. NR 2 TC 0 Z9 1 U1 0 U2 5 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2013 VL 11 IS 3 BP 357 EP 359 PG 3 WC Oncology SC Oncology GA 105AG UT WOS:000316037400013 PM 23486460 ER PT J AU Deffebach, ME Fuss, C AF Deffebach, Mark E. Fuss, Cristina TI Ground Glass Nodules: Just the Beginning SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID FLEISCHNER-SOCIETY; GUIDELINES; MANAGEMENT C1 [Deffebach, Mark E.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Fuss, Cristina] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Deffebach, ME (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,P3PULM, Portland, OR 97201 USA. EM deffebac@ohsu.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAR PY 2013 VL 8 IS 3 BP 257 EP 258 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 107HG UT WOS:000316205600008 PM 23407555 ER PT J AU Birkelbach, M Ferraiolo, N Gheorghiu, L Pfaffle, HN Daly, B Ebright, MI Spencer, C O'Hara, C Whetstine, JR Benes, CH Sequist, LV Zou, L Dahm-Daphi, J Kachnic, LA Willers, H AF Birkelbach, Moritz Ferraiolo, Natalie Gheorghiu, Liliana Pfaeffle, Heike N. Daly, Benedict Ebright, Michael I. Spencer, Cheryl O'Hara, Carl Whetstine, Johnathan R. Benes, Cyril H. Sequist, Lecia V. Zou, Lee Dahm-Daphi, Jochen Kachnic, Lisa A. Willers, Henning TI Detection of Impaired Homologous Recombination Repair in NSCLC Cells and Tissues SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Homologous recombination; RAD51; Biomarker ID IONIZING-RADIATION; BREAST-CANCER; LUNG-CANCER; PATHWAY; BRCA1; PHOSPHORYLATION; INHIBITION; EXPRESSION; CISPLATIN; DEFECTS AB Introduction: Homologous recombination repair (HRR) is a critical pathway for the repair of DNA damage caused by cisplatin or poly-ADP ribose polymerase (PARP) inhibitors. HRR may be impaired by multiple mechanisms in cancer, which complicates assessing the functional HRR status in cells. Here, we monitored the ability of non-small-cell lung cancer (NSCLC) cells to form subnuclear foci of DNA repair proteins as a surrogate of HRR proficiency. Methods: We assessed clonogenic survival of 16 NSCLC cell lines in response to cisplatin, mitomycin C (MMC), and the PARP inhibitor olaparib. Thirteen tumor explants from patients with NSCLC were subjected to cisplatin ex vivo. Cells were assayed for foci of repair-associated proteins such as BRCA1, FANCD2, RAD51, and gamma-H2AX. Results: Four cell lines (25%) showed an impaired RAD51 foci-forming ability in response to cisplatin. Impaired foci formation correlated with cellular sensitivity to cisplatin, MMC and olaparib. Foci responses complemented or superseded genomic information suggesting alterations in the ATM/ATR and FA/BRCA pathways. Because baseline foci in untreated cells did not predict drug sensitivity, we adapted an ex vivo biomarker assay to monitor damageinduced RAD51 foci in NSCLC explants from patients. Ex vivo cisplatin treatment of explants identified two tumors (15%) exhibiting compromised RAD51 foci induction. Conclusions: A fraction of NSCLC harbors HRR defects that may sensitize the affected tumors to DNA-damaging agents including PARP inhibitors. We propose that foci-based functional biomarker assays represent a powerful tool for prospective determination of treatment sensitivity, but will require ex vivo techniques for induction of DNA damage to unmask the underlying HRR defect. C1 [Birkelbach, Moritz; Ferraiolo, Natalie; Gheorghiu, Liliana; Pfaeffle, Heike N.; Kachnic, Lisa A.; Willers, Henning] Massachusetts Gen Hosp, Lab Cellular & Mol Radiat Oncol, Dept Radiat Oncol, Ctr Canc, Charlestown, MA USA. [Birkelbach, Moritz; Dahm-Daphi, Jochen] Univ Med Ctr Hamburg Eppendorf, Lab Radiobiol & Expt Radiat Oncol, Hamburg, Germany. [Daly, Benedict; Ebright, Michael I.] Boston Med Ctr, Dept Surg, Boston, MA USA. [Spencer, Cheryl; O'Hara, Carl] Boston Med Ctr, Dept Pathol, Boston, MA USA. [Whetstine, Johnathan R.; Benes, Cyril H.; Zou, Lee] Massachusetts Gen Hosp, Ctr Canc Res, Ctr Canc, Charlestown, MA USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Dahm-Daphi, Jochen] Univ Marburg, Inst Radiobiol & Mol Radiat Oncol, Marburg, Germany. [Kachnic, Lisa A.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. RP Willers, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3,55 Fruit St, Boston, MA 02114 USA. EM hwillers@partners.org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Department of Defense [W81XWH-06-1-0309]; Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer [NCI P50 CA090578, NCI R01 GM097360]; Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267]; Ellison Medical Foundation; German Cancer Aid (Deutsche Krebshilfe) [108903] FX This work was supported by the Department of Defense W81XWH-06-1-0309 (L.A.K., H.W.), the Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, NCI P50 CA090578 (L.Z., H.W.), NCI R01 GM097360 (J.W.), the Federal Share of program income earned by the Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center (J.W., L.Z., L.S., H.W.), the Ellison Medical Foundation (J.W.), and by the German Cancer Aid (Deutsche Krebshilfe) 108903 (J.D.D.). The authors declare no conflict of interest. NR 26 TC 18 Z9 19 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAR PY 2013 VL 8 IS 3 BP 279 EP 286 DI 10.1097/JTO.0b013e31827ecf83 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 107HG UT WOS:000316205600011 PM 23399959 ER PT J AU Wong, ML Clarke, CA Yang, J Hwang, J Hiatt, RA Wang, S AF Wong, Melisa L. Clarke, Christina A. Yang, Juan Hwang, Jimmy Hiatt, Robert A. Wang, Sunny TI Incidence of Non-Small-Cell Lung Cancer among California Hispanics According to Neighborhood Socioeconomic Status SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small-cell lung cancer; Incidence; Socioeconomic status; Hispanic Americans; Race and ethnicity ID CIGARETTE-SMOKING BEHAVIOR; ENGLISH-LANGUAGE USE; UNITED-STATES; EDUCATION; PATTERNS; MORTALITY; WOMEN; ACCULTURATION; BELIEFS; GENDER AB Introduction: Lung cancer incidence is associated with markers of lower socioeconomic status (SES) in whites, blacks, and Asians but with markers of higher SES in Hispanics. The magnitude and etiology of this positive gradient in Hispanics remain undefined. We examined non-small-cell lung cancer (NSCLC) incidence and eversmoking rates among California Hispanics according to measures of SES. Methods: We computed neighborhood (n) SES-specific incidence rates by sex and race or ethnicity for 74,179 NSCLC cases in the California Cancer Registry, 1998-2002. Associations between nSES and NSCLC incidence were examined, using incidence rate ratios and linear trend tests, and stratified by age, stage, and histology. Ever-smoking rates among Hispanics were obtained from California Health Interview Survey 2001 data, and odds ratios for ever-smoking were calculated for measures of SES and acculturation. Results: Compared with the lowest nSES quintile, the NSCLC incidence in the highest quintile was 1.86 and 1.18 times higher for Hispanic women and men, respectively. The positive nSES gradients remained significant for all ages, stages, and nonsquamous histologies in women, and only for older age, local or regional stages, and adenocarcinoma histology in men. Ever-smoking rates were associated with English-speaking households and U.S.-born status for Hispanic women and low education and U.S.-born status for Hispanic men. Conclusions: For California Hispanics, higher nSES was strongly associated with increased NSCLC incidence in women, but weakly associated in men, and ever-smoking rates were strongly correlated with increased acculturation. This finding may portend an increasing burden of NSCLC in Hispanic women, given future trends in acculturation and SES. C1 [Wong, Melisa L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Clarke, Christina A.; Yang, Juan] Canc Prevent Inst Calif, Fremont, CA USA. [Clarke, Christina A.] Stanford Canc Ctr, Dept Med, Stanford, CA USA. [Hwang, Jimmy; Hiatt, Robert A.; Wang, Sunny] Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Hiatt, Robert A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Wang, Sunny] San Francisco VA Med Ctr, Dept Med, Div Hematol & Oncol, San Francisco, CA 94121 USA. RP Wang, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111H1, San Francisco, CA 94121 USA. EM sunny.wang@ucsf.edu FU California Department of Public Health; National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000036C, HHSN261201000035C, HHSN261201000034C, HHSN261201000040C]; Centers for Disease Control and Prevention's National Program of Cancer Registries [1U58 DP000807-01]; University of California, San Francisco Pathways Funding Agency, Philip R. Lee Program; Northern California Institute for Research and Education (NCIRE), San Francisco VA Medical Center; University of California, San Francisco Pathways Funding Agency, Philip R. Lee Program, University of California, San Francisco, Department of Medicine; University of California, San Francisco Helen Diller Comprehensive Cancer Center FX Drs. Clarke and Yang's efforts on this project and the collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000036C awarded to the Northern California Cancer Center, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #1U58 DP000807-01 awarded to the Public Health Institute.; This work is supported by the National Cancer Institute's Surveillance, Epidemiology and End Results program under contract HHSN261201000040C awarded to the Cancer Prevention Institute of California; the University of California, San Francisco Pathways Funding Agency, Philip R. Lee Program; and the Northern California Institute for Research and Education (NCIRE), San Francisco VA Medical Center.; Dr. Wong's efforts on this project were supported by the University of California, San Francisco Pathways Funding Agency, Philip R. Lee Program, University of California, San Francisco, Department of Medicine. Dr. Wang's efforts on this project were supported by the Northern California Institute for Research and Education, San Francisco VA Medical Center, and the University of California, San Francisco Helen Diller Comprehensive Cancer Center. All the other authors declare no conflict of interest. NR 36 TC 2 Z9 2 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAR PY 2013 VL 8 IS 3 BP 287 EP 294 DI 10.1097/JTO.0b013e31827bd7f5 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 107HG UT WOS:000316205600012 PM 23399956 ER PT J AU Sholl, LM Weremowicz, S Gray, SW Wong, KK Chirieac, LR Lindeman, NI Hornick, JL AF Sholl, Lynette M. Weremowicz, Stanislawa Gray, Stacy W. Wong, Kwok-Kin Chirieac, Lucian R. Lindeman, Neal I. Hornick, Jason L. TI Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK-Rearranged Lung Adenocarcinomas SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Anaplastic lymphoma kinase; Lung adenocarcinoma; Fluorescence in situ hybridization; Immunohistochemistry ID CANCER PATIENTS; FUSION; EGFR; MUTATIONS; GEFITINIB AB Introduction: ALK gene rearrangements occur in approximately 5% of lung adenocarcinomas (ACAs), leading to anaplastic lymphoma kinase (ALK) overexpression and predicting response to targeted therapy. Fluorescence in situ hybridization (FISH) is the standard procedure for detection of ALK rearrangements in lung ACA but requires specialized equipment and expertise. Immunohistochemistry (IHC) for ALK protein overexpression is a promising screening modality, with reports of newer antibodies showing excellent sensitivity and specificity for ALK-rearranged lung ACA. Methods: In this study, we analyzed ALK IHC (5A4 clone) in 186 cases from our clinical service and compared it with ALK FISH and EGFR and KRAS mutation status. Results: Twelve cases had concordant ALK protein overexpression and ALK rearrangement by FISH. Three ALK-rearranged cases lacked ALK protein expression. Of these discrepant cases, one had a coexisting EGFR mutation and a subtle atypical ALK rearrangement manifested as a break in the 5' centromeric portion of the FISH probe. One case had a concurrent BRAF mutation. Follow-up testing on a metastasis revealed absence of the ALK rearrangement, with persistent BRAF mutation. In one ALK-rearranged protein negative case, very limited tissue remained for ALK IHC, raising the possibility of false negativity because of protein expression heterogeneity. Importantly, ALK protein expression was detected in one case initially thought not to have an ALK rearrangement. In this case, FISH was falsely negative because of interference by benign reactive nuclei. After correcting for these cases, ALK IHC was 93% sensitive and 100% specific as compared with FISH. Conclusions: ALK IHC improves the detection of ALK rearrangements when used together with FISH, and its use in lung ACA genetic testing algorithms should be considered. C1 [Sholl, Lynette M.; Weremowicz, Stanislawa; Chirieac, Lucian R.; Lindeman, Neal I.; Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gray, Stacy W.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Thorac Oncol, Boston, MA 02115 USA. RP Sholl, LM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lmsholl@partners.org OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [P50 CA090578] NR 17 TC 72 Z9 73 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAR PY 2013 VL 8 IS 3 BP 322 EP 328 DI 10.1097/JTO.0b013e31827db604 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 107HG UT WOS:000316205600017 PM 23407557 ER PT J AU Hirsch, FR Janne, PA Eberhardt, WE Cappuzzo, F Thatcher, N Pirker, R Choy, H Kim, ES Paz-Ares, L Gandara, DR Wu, YL Ahn, MJ Mitsudomi, T Shepherd, FA Mok, TS AF Hirsch, Fred R. Jaenne, Pasi A. Eberhardt, Wilfried E. Cappuzzo, Federico Thatcher, Nick Pirker, Robert Choy, Hak Kim, Edward S. Paz-Ares, Luis Gandara, David R. Wu, Yi-Long Ahn, Myung-Ju Mitsudomi, Tetsuya Shepherd, Frances A. Mok, Tony S. TI Epidermal Growth Factor Receptor Inhibition in Lung Cancer Status 2012 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Review DE EGFR antibodies; Carcinoma; non-small-cell lung; Molecular targeted therapy; Epidermal growth factor receptor; Tyrosine kinase inhibitors ID PHASE-III TRIAL; TYROSINE KINASE INHIBITORS; PLATINUM-BASED CHEMOTHERAPY; PREVIOUSLY TREATED PATIENTS; ACQUIRED-RESISTANCE; 1ST-LINE CHEMOTHERAPY; MET AMPLIFICATION; MOLECULAR PREDICTORS; RANDOMIZED-TRIAL; EGFR MUTATION AB Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing. C1 [Hirsch, Fred R.] Univ Colorado, Dept Med, Div Med Oncol, Ctr Canc, Aurora, CO 80045 USA. [Hirsch, Fred R.] Univ Colorado, Dept Pathol, Ctr Canc, Aurora, CO 80045 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Eberhardt, Wilfried E.] West German Canc Ctr, Dept Med Canc Res, Essen, Germany. [Cappuzzo, Federico] Osped Civile, Dept Oncol, Inst Toscano Tumori, Venice, Livorno, Italy. [Thatcher, Nick] Christie Hosp NHS Trust, Dept Med Oncol, Manchester M20 4BX, Lancs, England. [Pirker, Robert] Med Univ Vienna, Dept Med 1, Vienna, Austria. [Choy, Hak] Univ Texas SW Med Ctr Dallas, Dept Therapeut Radiat Oncol, Dallas, TX 75390 USA. [Kim, Edward S.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Paz-Ares, Luis] Univ Hosp Virgen del Rocio, Dept Med, Inst Biomed Sevilla, Seville, Spain. [Gandara, David R.] UC Davis Canc Ctr, Dept Internal Med, Div Hematol Oncol, Sacramento, CA USA. [Gandara, David R.] UC Davis Canc Ctr, Dept Radiat Oncol, Sacramento, CA USA. [Wu, Yi-Long] Guangdong Gen Hosp, Dept Med, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Wu, Yi-Long] Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China. [Ahn, Myung-Ju] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hematol Oncol, Seoul, South Korea. [Mitsudomi, Tetsuya] Kinki Univ, Dept Surg, Div Thorac Surg, Sch Med, Higashiosaka, Osaka 577, Japan. [Shepherd, Frances A.] Princess Margaret Hosp, Dept Med, Div Med Oncol & Hematol, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. [Shepherd, Frances A.] Univ Toronto, Toronto, ON, Canada. [Mok, Tony S.] Chinese Univ Hong Kong, Dept Clin Oncol, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. RP Hirsch, FR (reprint author), Univ Colorado, Dept Med, Div Med Oncol, Ctr Canc, 12801 E 17th Ave, Aurora, CO 80045 USA. EM fred.hirsch@ucdenver.edu RI IBIS, NUEVAS TERAPIA/P-3415-2015; OI Wu, Yi-Long/0000-0002-3611-0258; Cappuzzo, Federico/0000-0002-6295-6767; Mitsudomi, Tetsuya/0000-0001-9860-8505 FU Roche; AstraZeneca; Biodesix; ImClone; Eli Lilly, Celgene; Morphotek; OSI Pharmaceuticals; Boehringer Ingelheim; Genentech; Merrimack; Italian Association for Cancer research. FX This review was based on an EGFR summit held in London in 2011 and since updated with the most recent data. The EGFR summit was supported by unrestricted grants from Roche, AstraZeneca, and Biodesix.; Dr. Hirsch is a consultant on advisory boards to Genentech-Roche, Boehringer-Ingelheim, Bristol-Myers Squibb, ImClone, Celgene, Eli Lilly, Merck-Serono, and Pfizer, has received research funding for the laboratory (through the University of Colorado) from ImClone, Eli Lilly, Celgene, Morphotek, OSI Pharmaceuticals, and AstraZeneca, and is co-inventor of a University of Colorado-owned patent: EGFR biomarker (IHC, FISH) for predicting outcome to EGFR inhibitors, which is licensed to Abbott Laboratories. Dr. Jenne is a consultant on advisory boards to Roche, Genentech, AstraZeneca, Boehringer-Ingelheim, Pfizer, and Sanofi, and has a relationship to LabCorp. Dr. Eberhardt received travel support and fees for participation in review activities from AstraZeneca, is a member of an advisory board or a consultant for AstraZeneca, Roche, Boehringer Ingelheim, Amgen, Pfizer, GlaxoSmithKline, MerckSerono, Merck, Novartis and Eli Lilly, and a grant from Eli Lilly. He was also paid for lectures including speakers bureaus from Eli Lilly, AstraZeneca, Boehringer Ingelheim, Pfizer, Amgen, Merck, MerckSerono, Pierre Fabre, and Teva Pharmaceuticals. Dr. Cappuzzo was a consultant to Roche, AstraZeneca, and Eli Lilly. Dr. Thatcher has received honoraria for board membership, consultancy, payment for lectures including speaker bureaus, travel accommodations and meeting expenses from AstraZeneca and Roche, and expert testimony from Roche. Dr. Pirker has a compensated consultancy role with AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Merck-Serono, and Roche and has received payments for lectures or service on speakers' bureaus from Merck-Serono and travel support from Boehringer-Ingelheim. Dr. Kim was a consultant for Boehringer-Ingelheim and Roche. Dr. Paz-Ares received expert testimony from Roche, AstraZeneca, Lilly, Pfizer, and Merck. Dr. Gandara has received grants from Genentech and Merrimack, was or is a consultant for Bristol-Myers Squibb and Pfizer, has received payments for lectures (including service on speaker bureaus) from AstraZeneca and travel support from Pfizer. Dr. Wu has received payments for lectures (including service on speaker bureaus) from Roche, AstraZeneca, Pfizer, Eli Lilly, and Sanofi-Aventis.. Dr. Mitsudomi was a consultant for AstraZeneca, Boehringer-Ingelheim, Chugai, Roche, Pfizer, and Eli Lilly. He received payments for lectures (including service on speaker bureaus) from Taiho, Sanofi-Aventis, Kyowa-Hakko, and Daiichi-Sankyo. Dr. Shepherd is a consultant for Roche, and was a consultant for AstraZeneca and Merck. She received payments for lectures (including service on speaker bureaus) from Roche. Dr. Mok is a consultant for Roche, Pfizer, Taiho, Novartis, Janssen, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Eisai, and MerckSerono, received research funding from AstraZeneca, was paid for lectures (including service on speaker bureaus) from Janssen and Novartis, received fees for participation in review activities (such as data monitoring boards, statistical analysis, end point committees) from Roche, and received a grant from AstraZeneca. Dr. Cappuzzo was supported in part by the Italian Association for Cancer research. All other authors declare no conflicts of interest NR 113 TC 58 Z9 59 U1 0 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAR PY 2013 VL 8 IS 3 BP 373 EP 384 DI 10.1097/JTO.0b013e31827ed0ff PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 107HG UT WOS:000316205600025 PM 23370315 ER PT J AU Bigatello, LM Amirfarzan, H Haghighi, AK Newhouse, B Del Rio, JM Allen, K Chang, A Schmidt, U Razavi, M AF Bigatello, Luca M. Amirfarzan, Houman Haghighi, Asieh Kazem Newhouse, Beverly Del Rio, J. Mauricio Allen, Kathrin Chang, Anne Schmidt, Ulrich Razavi, Moaven TI Effects of routine monitoring of delirium in a surgical/trauma intensive care unit SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE ICU delirium; diagnostic instruments for delirium; CAM-ICU; delirium in surgical patients; delirium in trauma patients ID CRITICALLY-ILL PATIENTS; MECHANICALLY VENTILATED PATIENTS; CONFUSION ASSESSMENT METHOD; TRAUMA PATIENTS; SEDATION; RELIABILITY; MANAGEMENT; ICU; IMPLEMENTATION; EFFICACY AB BACKGROUND: Delirium is prevalent in surgical and trauma intensive care units (ICUs) and carries substantial morbidity. This study tested the hypothesis that daily administration of a diagnostic instrument for delirium in a surgical/trauma ICU decreases the time of institution of pharmacologic therapy and improves related outcomes. METHODS: Controlled trial of two concurrent groups. The Confusion-Assessment Method for ICU was administered daily to all eligible patients admitted to our surgical/trauma ICU for 48 hours or longer. The result was communicated to one of the two preexisting ICU services (intervention service) and not the other (control service). Primary outcome was the time between diagnosis of delirium and pharmacologic treatment. Secondary outcomes included duration of delirium, mechanical ventilation, and ICU stay. RESULTS: Delirium occurred in 98 (35%) of 283 consecutive patients. Time between diagnosis and therapy did not differ between intervention (35 [35] hours) and control (40 [41] hours) groups. There was a difference in the number of delirium days treated in the intervention (73%) versus control (64%) groups (p = 0.035). The intervention group had significantly lower odds to neglect treating delirium when delirium was present (odds ratio, 0.67; 95% confidence interval, 0.45-1.00; p = 0.05). In the subgroup of trauma patients, the odds ratio of negligence was 0.37 (95% confidence interval, 0.14-0.99; p = 0.048), indicating lower probability for trauma patients to be untreated. There was no difference in the average duration of delirium, mechanical ventilation, and ICU stay. CONCLUSION: In our surgical/trauma ICU, daily screening for delirium did not affect the timing of pharmacologic therapy. Although the intervention resulted in a higher number of delirious ICU patients being treated, particularly trauma patients, there was no effect on related outcomes. (J Trauma Acute Care Surg. 2013;74: 876-883. Copyright (c) 2013 by Lippincott Williams & Wilkins) C1 [Bigatello, Luca M.; Haghighi, Asieh Kazem] St Elizabeths Med Ctr, Dept Anesthesiol & Pain Med, Boston, MA 02135 USA. [Bigatello, Luca M.; Haghighi, Asieh Kazem] Tufts Univ, Sch Med, Medford, MA USA. [Amirfarzan, Houman] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Schmidt, Ulrich] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Chang, Anne] Newton Wellesley Hosp, Newton, MA USA. [Razavi, Moaven] Brandeis Univ, Heller Sch, Schneider Inst Hlth Policy, Waltham, MA 02254 USA. [Newhouse, Beverly] Univ Calif San Diego, Dept Anesthesia, San Diego, CA 92103 USA. [Del Rio, J. Mauricio] Duke Univ, Dept Anesthesiol, Durham, NC USA. [Allen, Kathrin] W Virginia Univ, Dept Anesthesia, Morgantown, WV 26506 USA. RP Bigatello, LM (reprint author), St Elizabeths Med Ctr, Dept Anesthesiol & Pain Med, 376 Cambridge St, Boston, MA 02135 USA. EM luca.bigatello@Steward.org FU Clinical Innovation Award of the Massachusetts General Hospital FX This study was funded by a Clinical Innovation Award of the Massachusetts General Hospital (to L.M.B.). NR 32 TC 9 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAR PY 2013 VL 74 IS 3 BP 876 EP 883 DI 10.1097/TA.0b013e31827e1b69 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 108UO UT WOS:000316321900033 PM 23425751 ER PT J AU Henry, AJ Hevelone, ND Hawkins, AT Watkins, MT Belkin, M Nguyen, LL AF Henry, Antonia J. Hevelone, Nathanael D. Hawkins, Alexander T. Watkins, Michael T. Belkin, Michael Nguyen, Louis L. TI Factors predicting resource utilization and survival after major amputation SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID UNITED-STATES; LIMB SALVAGE; ISCHEMIA; OUTCOMES; COSTS; CHEMOTHERAPY; MORTALITY; EVENTS; CANCER; BYPASS AB Objective: Major amputation is associated with increased short-term healthcare resource utilization (RU), early mortality, and socioeconomic status (SES) disparities. Our objective is to study patient-specific and SES-related predictors of long-term RU and survival after amputation. Methods: This retrospective analysis identified 364 adult patients who underwent index major amputation for critical limb ischemia from January 1995 through December 2000 at two tertiary centers with outcomes through December 2010. Age, gender, SES (race, income, insurance, and marital status), comorbidities (congestive heart failure [CHF], diabetes, diabetes with complications, and renal failure [RF]), subsequent procedures, cumulative length of stay (cLOS), and mortality were analyzed. Bivariate and multivariate Poisson regression for subsequent procedures and cLOS and Cox proportional hazard modeling for all-cause mortality were undertaken. Results: During a mean follow-up of 3.25 years, amputation patients had mean cLOS of 71.2 days per person-year (median, 17.6), 19.5 readmissions per person-year (median, 2.1), 0.57 amputation-related procedures (median, 0), and 0.31 cardiovascular procedures (median, 0). Below-knee amputation as the index procedure was performed in 70% of patients, and 25% had additional amputation procedures. Of readmissions at <= 30 days, 52% were amputation-related. Overall mortality during follow-up was 86.9%; 37 patients (10.2%) died within 30 days. Among patients surviving >30 days, multivariate Poisson regression demonstrated that younger age (incidence rate ratio [IRR], 0.98), public insurance (IRR, 1.63), CHF (IRR, 1.60), and RF (IRR, 2.12) were associated with increased cLOS. Diabetes with complications (IRR, 1.90) and RF (IRR, 2.47) affected subsequent amputation procedures. CHF (IRR, 1.83) and RF (IRR, 3.67) were associated with a greater number of cardiovascular procedures. Cox proportional hazard modeling indicated older age (hazard ratio [HR], 1.04), CHF (HR, 2.26), and RF (HR, 2.60) were risk factors for decreased survival. Factors associated with SES were not significantly related to the outcomes. Conclusions: This study found that RU is high for amputees, and increased RU persists beyond the perioperative period. Results were similar across SES indices, suggesting higher SES may not be protective against poor outcomes when limb salvage is no longer attainable. These findings support the hypothesis that SES disparities may be more modifiable during earlier stages of care for critical limb ischemia. (J Vasc Surg 2013;57:784-90.) C1 [Henry, Antonia J.; Hevelone, Nathanael D.; Hawkins, Alexander T.; Belkin, Michael; Nguyen, Louis L.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hawkins, Alexander T.; Watkins, Michael T.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Henry, Antonia J.; Hawkins, Alexander T.; Watkins, Michael T.; Belkin, Michael; Nguyen, Louis L.] Harvard Univ, Sch Med, Boston, MA USA. RP Nguyen, LL (reprint author), Brigham & Womens Hosp, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA. EM llnguyen@partners.org OI Hevelone, Nathanael/0000-0003-4740-2085 FU NIH K23 Research Career Development Award [HL084386]; National Research Service Award T32 Institutional Research Training Grant [HL00734] FX This work was supported by NIH K23 Research Career Development Award (HL084386) (L.N.), and National Research Service Award T32 Institutional Research Training Grant (HL00734) (A.J.H). NR 19 TC 6 Z9 6 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 2013 VL 57 IS 3 BP 784 EP 790 DI 10.1016/j.jvs.2012.09.035 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 103UH UT WOS:000315944400030 PM 23312839 ER PT J AU Iverson, KM Pogoda, TK Gradus, JL Street, AE AF Iverson, Katherine M. Pogoda, Terri K. Gradus, Jaimie L. Street, Amy E. TI Deployment-Related Traumatic Brain Injury Among Operation Enduring Freedom/Operation Iraqi Freedom Veterans: Associations with Mental and Physical Health by Gender SO JOURNAL OF WOMENS HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; POLYTRAUMA CLINICAL TRIAD; PSYCHIATRIC DIAGNOSES; SERVICE MEMBERS; WAR VETERANS; COMBAT; MILITARY; AFGHANISTAN; CONCUSSION AB Background: Traumatic brain injury (TBI) research among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans has focused primarily on men. We examine associations between probable deployment-related TBI and postdeployment mental and physical health symptoms separately by gender. To identify unique associations of probable TBI with health symptoms, analyses were also conducted separately for veterans with and without probable posttraumatic stress disorder (PTSD). Methods: A mail survey, including self-report measures of probable deployment-related TBI and mental and physical health symptoms, was completed by 2348 OEF/OIF veterans (51% female), sampled randomly within gender from a national roster. We conducted logistic regressions stratified by gender and probable PTSD status to evaluate associations between probable TBI and health symptoms. Results: Of the respondents, 10.7% of women and 19.7% of men screened positive for probable deployment-related TBI. Probable TBI was significantly associated with increased risk of mental and physical health symptoms for both genders, even after adjusting for potential confounders. Odds ratios for the associations of probable TBI with health symptoms ranged between 2.63 and 9.20 for women and between 1.94 and 7.44 for men. Among veterans with probable PTSD, symptomatic anxiety and symptomatic physical health remained associated with probable TBI. Among veterans without probable PTSD, TBI remained strongly associated with all health symptoms for women and symptomatic anxiety and physical health for men, suggesting an association between TBI and some health symptoms independent of PTSD. Conclusions: Strong associations between probable TBI and health symptoms for women and men confirm the importance of screening for TBI and treatment of associated health symptoms for all OEF/OIF veterans. C1 [Iverson, Katherine M.; Gradus, Jaimie L.; Street, Amy E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Iverson, Katherine M.; Gradus, Jaimie L.; Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Pogoda, Terri K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Pogoda, Terri K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM katherine.iverson@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU National Center for PTSD, Mental Health Services, Department of Veterans Affairs; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSRD) Services [CDA 10-029] FX This research was supported by the National Center for PTSD, Mental Health Services, Department of Veterans Affairs. The funding agency was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. Additionally, the research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of Dr. Katherine Iverson's HSR&D Career Development Award (CDA 10-029). 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 51 TC 11 Z9 11 U1 2 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2013 VL 22 IS 3 BP 267 EP 275 DI 10.1089/jwh.2012.3755 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 105IU UT WOS:000316061700134 PM 23421581 ER PT J AU Stone, JH AF Stone, John H. TI IgG4: a tantalizing link between causes of membranous glomerulonephritis and systemic disease SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID IGG4-RELATED DISEASE; TUBULOINTERSTITIAL NEPHRITIS; AUTOIMMUNE PANCREATITIS; NEPHROPATHY AB Alexander et al. give a detailed description of IgG4-related membranous glomerulonephritis (MGN). Their data delineate for the first time in IgG4-related disease (IgG4-RD) a second pattern of tissue injury occurring within the same organ. The paper highlights that MGN can occur alone or simultaneously with IgG4-related tubulointerstitial nephritis. Thus, it extends our understanding of IgG4-RD and illuminates potential pathways for new investigations into its pathophysiology. Kidney International (2013) 83, 348-350. doi:10.1038/ki.2012.454 C1 [Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 14 TC 6 Z9 8 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2013 VL 83 IS 3 BP 348 EP 350 DI 10.1038/ki.2012.454 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 106PD UT WOS:000316156100003 PM 23446252 ER PT J AU Detappe, A Tsiamas, P Ngwa, W Zygmanski, P Makrigiorgos, M Berbeco, R AF Detappe, Alexandre Tsiamas, Panagiotis Ngwa, Wilfred Zygmanski, Piotr Makrigiorgos, Mike Berbeco, Ross TI The effect of flattening filter free delivery on endothelial dose enhancement with gold nanoparticles SO MEDICAL PHYSICS LA English DT Article DE gold nanoparticle; vascular-disrupting agent; flattening filter free; dose enhancement; Monte-Carlo ID VASCULAR DISRUPTING AGENTS; MONTE-CARLO; CANCER-THERAPY; RADIOTHERAPY AB Purpose: The aim of this study is to quantify and to compare the dose enhancement factor from gold nanoparticles (AuNP) to tumor endothelial cells for different concentrations of AuNP, and clinical MV beam configurations. Methods: Tumor endothelial cells are modeled as slabs measuring 10 x 10 x 2 mu m. A spherical AuNP is simulated on the surface of the endothelial cell, within the blood vessel. 6 MV photon beams with and without the flattening filter are investigated for different field sizes, depths in material and beam modulation. The incident photon energy spectra for each configuration is generated using EGSnrc. The dose enhancement in the tumor endothelial cell is found using an analytical calculation. The endothelial dose enhancement factor is defined to be the ratio of the dose deposited with and without AuNPs. Results: It is found that clinical beam parameters may be chosen to maximize the effect of gold nanoparticles during radiotherapy. This effect is further amplified similar to 20% by the removal of the flattening filter. Modulation of the clinical beam with the multileaf collimator tends to decrease the proportion of low energy photons, therefore providing less enhancement than the corresponding open field. Conclusions: The results of this work predict a dose enhancement to tumor blood vessel endothelial cells using conventional therapeutic (MV) x-rays and quantify the relative change in enhancement with treatment depth and field size. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4791671] C1 [Detappe, Alexandre; Tsiamas, Panagiotis; Ngwa, Wilfred; Zygmanski, Piotr; Makrigiorgos, Mike; Berbeco, Ross] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Detappe, Alexandre; Tsiamas, Panagiotis; Ngwa, Wilfred; Zygmanski, Piotr; Makrigiorgos, Mike; Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Detappe, Alexandre] Univ Grenoble 1, Dept Med Phys, Grenoble 38000, France. [Tsiamas, Panagiotis] Univ Thessaly, Sch Med, Dept Med Phys, Larisa 41100, Greece. RP Detappe, A (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM rberbeco@lroc.harvard.edu OI Detappe, Alexandre/0000-0001-9364-1621 FU Brigham and Women's Hospital Biomedical Research Institute Seed Grant; National Cancer Institute [R03CA164645] FX The project described was supported, in part, by a Brigham and Women's Hospital Biomedical Research Institute Seed Grant and by Award No. R03CA164645 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 22 TC 8 Z9 9 U1 0 U2 15 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2013 VL 40 IS 3 AR 031706 DI 10.1118/1.4791671 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109LG UT WOS:000316369400009 PM 23464301 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Monte Carlo assessment of CT dose equilibration in PMMA and water cylinders with diameters from 6 to 55 cm SO MEDICAL PHYSICS LA English DT Article DE computed tomography (CT); dose; equilibration; mathematical model; calculation ID ATTENUATION-BASED ESTIMATION; COMPUTED-TOMOGRAPHY; PRACTICAL APPROACH; PATIENT SIZE; DOSIMETRY; VALIDATION; EQUATIONS; PROFILES; INFINITY; PURPOSE AB Purpose: In multidetector CT, the dose integral DIL, of single scan dose profile over the integration interval (-L/2, L/2) can predict the accumulated dose D-L(0) at the center of the scan range (-L/2, L/2) for a helical scan of pitch = 1. Both DIL, and DL(0) increase with L until the limiting levels (DI infinity and D-eq) are reached. The DL(0) equilibration is related to the DIL equilibration. The aim of this study was to evaluate the DIL/DI infinity growth curve, and its variations with factors such as phantom diameter, phantom axis (center or periphery), material (PMMA or water), tube voltage, and. bowtie filter (head or body). Methods: A Geant4-based Monte Carlo program was used to simulate single axial scans on a clinical CT scanner, and to compute axial dose profiles in the cylinders of 90 cm in length, and 6-50 cm (PMMA) and 6-55 cm (water) in diameters. DIL/DI infinity ratios were calculated over a range of integration lengths, and were fitted to a mathematical model: f (L) = 1 - alpha x exp[-(L/d)(n)], where alpha, d, and n were fitting parameters. The minimum length required for DIL to approach within 2% of DI infinity was referred to as the equilibrium length L-eq. It could be directly derived from data, and was also calculated from the fits. Results: The L-eq results of the above two approaches were consistent (deviation: 1.4% on average, and 3.6% maximum). When the other conditions (such as tube voltage, bowtie filter, and phantom material) were the same, DI infinity increased with the reduced phantom diameters. The center/periphery DI infinity ratio was greater than 1 for small phantoms, and increased with larger phantoms until their diameters were above about 16 cm. Dose to water was substantially higher than that to PMMA, especially at the centers of large phantoms. As phantom diameter increased, alpha, n, and L-eq increased on the central axis, and initially increased and then saturated [alpha approximate to 0.555 (PMMA and water), n approximate to 0.81 (PMMA) and 0.80 (water), and L-eq approximate to 29 cm (PMMA) and 30 cm (water)] on the peripheral axis. Bowtie filter and tube voltage affected dose, but had small effects on alpha, n, and L-eq. L-eg was almost constant on the central or peripheral phantom axis for beam widths from 0.1 to 40 mm Conclusions: The mathematical model can represent the DIL/DI infinity curve from a single axial CT scan. Generally, n not equal 1. The equilibrium dose, alpha, n, and L-eq exhibit strong dependencies on phantom diameter and location in the phantom. On the other hand, alpha, n, and L-eq have relatively weak dependencies on material (PMMA or water), tube voltage (80-140 kVp), and bowtie filter, and L-eq is also insensitive to beam width (<= 4 cm). A weak dependency of the DIL/DI infinity curve on CT scanner using 80-140 kVp and beam width up to 4 cm is consistent with the results of this study and previous publications. The dose equilibration data provided in this paper can be useful for CT dose evaluation. A framework is presented for assessing dose at any point in infinitely long PMMA and water cylinders undergoing multidetector CT examinations. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4790470] C1 [Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Webster Ctr Adv Res & Educ Radiat, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 17 TC 13 Z9 13 U1 1 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2013 VL 40 IS 3 AR 031903 DI 10.1118/1.4790470 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109LG UT WOS:000316369400026 PM 23464318 ER PT J AU Cibulskis, K Lawrence, MS Carter, SL Sivachenko, A Jaffe, D Sougnez, C Gabriel, S Meyerson, M Lander, ES Getz, G AF Cibulskis, Kristian Lawrence, Michael S. Carter, Scott L. Sivachenko, Andrey Jaffe, David Sougnez, Carrie Gabriel, Stacey Meyerson, Matthew Lander, Eric S. Getz, Gad TI Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples SO NATURE BIOTECHNOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; SEQUENCING DATA; LUNG ADENOCARCINOMA; PANCREATIC-CANCER; PROSTATE-CANCER; GENOME; EVOLUTION; TUMOR; LANDSCAPE; DISCOVERY AB Detection of somatic point substitutions is a key step in characterizing the cancer genome. However, existing methods typically miss low-allelic-fraction mutations that occur in only a subset of the sequenced cells owing to either tumor heterogeneity or contamination by normal cells. Here we present MuTect, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity. We also describe benchmarking approaches that use real, rather than simulated, sequencing data to evaluate the sensitivity and specificity as a function of sequencing depth, base quality and allelic fraction. Compared with other methods, MuTect has higher sensitivity with similar specificity, especially for mutations with allelic fractions as low as 0.1 and below, making MuTect particularly useful for studying cancer subclones and their evolution in standard exome and genome sequencing data. C1 [Cibulskis, Kristian; Lawrence, Michael S.; Carter, Scott L.; Sivachenko, Andrey; Jaffe, David; Sougnez, Carrie; Gabriel, Stacey; Meyerson, Matthew; Lander, Eric S.; Getz, Gad] Broad Inst Harvard, Cambridge, MA USA. [Cibulskis, Kristian; Lawrence, Michael S.; Carter, Scott L.; Sivachenko, Andrey; Jaffe, David; Sougnez, Carrie; Gabriel, Stacey; Meyerson, Matthew; Lander, Eric S.; Getz, Gad] MIT, Cambridge, MA 02139 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Getz, G (reprint author), Broad Inst Harvard, Cambridge, MA USA. EM gadgetz@broadinstitute.org FU US National Institutes of Health [U54HG003067, U24CA143845] FX This work was supported by US National Institutes of Health grants U54HG003067 and U24CA143845. We thank the Genome Analysis ToolKit (GATK) group, and our beta test users for their valuable feedback. NR 45 TC 582 Z9 587 U1 7 U2 78 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2013 VL 31 IS 3 BP 213 EP 219 DI 10.1038/nbt.2514 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 110JX UT WOS:000316439500014 PM 23396013 ER PT J AU Hwang, WY Fu, YF Reyon, D Maeder, ML Tsai, SQ Sander, JD Peterson, RT Yeh, JRJ Joung, JK AF Hwang, Woong Y. Fu, Yanfang Reyon, Deepak Maeder, Morgan L. Tsai, Shengdar Q. Sander, Jeffry D. Peterson, Randall T. Yeh, J-R Joanna Joung, J. Keith TI Efficient genome editing in zebrafish using a CRISPR-Cas system SO NATURE BIOTECHNOLOGY LA English DT Article ID ZINC-FINGER NUCLEASES; TALENS; PROKARYOTES; BACTERIA; IMMUNITY AB In bacteria, foreign nucleic acids are silenced by clustered, regularly interspaced, short palindromic repeats (CRISPR) CRISPR-associated (Gas) systems. Bacterial type II CRISPR systems have been adapted to create guide RNAs that direct site-specific DNA cleavage by the Cas9 endonuclease in cultured cells. Here we show that the CRISPR-Cas system functions in vivo to induce targeted genetic modifications in zebrafish embryos with efficiencies similar to those obtained using zinc finger nucleases and transcription activator like effector nucleases. C1 [Hwang, Woong Y.; Peterson, Randall T.; Yeh, J-R Joanna] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Fu, Yanfang; Reyon, Deepak; Maeder, Morgan L.; Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. [Fu, Yanfang; Reyon, Deepak; Maeder, Morgan L.; Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Fu, Yanfang; Reyon, Deepak; Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Peterson, Randall T.; Yeh, J-R Joanna] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Yeh, J-R Joanna] Broad Inst, Cambridge, MA USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. EM jyeh1@partners.org; jjoung@partners.org FU US National Institutes of Health (NIH) [DP1 GM105378]; NIH [R01 GM088040, P50 HG005550, K01 AG031300]; Jim and Ann Orr Research Scholar Award; Massachusetts General Hospital FX This work was supported by a US National Institutes of Health (NIH) Director's Pioneer Award DP1 GM105378 (J.K.J.), NIH R01 GM088040 (J.K.J. & R.T.P.), NIH P50 HG005550 (J.K.J.), the Jim and Ann Orr Research Scholar Award (J.K.J.), NIH K01 AG031300 (J.-R.J.Y.) and a Massachusetts General Hospital Claflin award (J.-R.J.Y.). We thank G. Church, J. Aach and P. Mali for sharing unpublished results and helpful discussions. NR 20 TC 869 Z9 967 U1 127 U2 728 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2013 VL 31 IS 3 BP 227 EP 229 DI 10.1038/nbt.2501 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 110JX UT WOS:000316439500016 PM 23360964 ER PT J AU McMillin, DW Negri, JM Mitsiades, CS AF McMillin, Douglas W. Negri, Joseph M. Mitsiades, Constantine S. TI The role of tumour-stromal interactions in modifying drug response: challenges and opportunities SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID CELL LUNG-CANCER; BONE-MARROW MICROENVIRONMENT; CHRONIC LYMPHOCYTIC-LEUKEMIA; RAF INHIBITOR RESISTANCE; MESENCHYMAL STEM-CELLS; ROUS-SARCOMA-VIRUS; MULTIPLE-MYELOMA; KINASE INHIBITORS; OVARIAN-CANCER; MOUSE MODEL AB The role of stromal cells and the tumour nnicroenvironnnent in general in modulating tumour sensitivity is increasingly becoming a key consideration for the development of active anticancer therapeutics. Here, we discuss how these tumour stromal interactions affect tumour cell signalling, survival, proliferation and drug sensitivity. Particular emphasis is placed on the ability of stromal cells to confer - to tumour cells - resistance or sensitization to different classes of therapeutics, depending on the specific microenvironmental context. The mechanistic understanding of these microenvironmental interactions can influence the evaluation and selection of candidate agents for various cancers, in both the primary site as well as the metastatic setting. Progress in in vitro screening platforms as well as orthotopic and 'orthometastatic' xenograft mouse models has enabled comprehensive characterization of the impact of the tumour nnicroenvironment on therapeutic efficacy. These recent advances can hopefully bridge the gap between preclinical studies and clinical trials of anticancer agents. C1 [McMillin, Douglas W.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [McMillin, Douglas W.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [McMillin, Douglas W.] Axios Biosci, Cambridge, MA 02139 USA. [Negri, Joseph M.] Harvard Univ, Sch Med, Biol & Biomed Sci Fac, Boston, MA 02115 USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM constantine_mitsiades@dfci.harvard.edu FU US National Institutes of Health [RO1-50947] FX The authors thank A. L Kung and N. S. Gray for their suggestions during the preparation of this manuscript. This study was supported by the US National Institutes of Health (grant RO1-50947 to C.S.M.). NR 148 TC 118 Z9 118 U1 4 U2 63 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD MAR PY 2013 VL 12 IS 3 BP 217 EP 228 DI 10.1038/nrd3870 PG 12 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 105BT UT WOS:000316041300021 PM 23449307 ER PT J AU Stuart, LM Paquette, N Boyer, L AF Stuart, Lynda M. Paquette, Nicholas Boyer, Laurent TI Effector-triggered versus pattern-triggered immunity: how animals sense pathogens SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID PORE-FORMING TOXINS; DAMAGE-RESPONSE FRAMEWORK; BACTERIAL EFFECTORS; INNATE IMMUNITY; TRANSLATIONAL INHIBITION; MICROBIAL PATHOGENESIS; LEGIONELLA-PNEUMOPHILA; ACTIVATION; RECOGNITION; DANGER AB A fundamental question regarding any immune system is how it can discriminate between pathogens and non-pathogens. Here, we discuss how this discrimination can be mediated by a surveillance system distinct from pattern-recognition receptors that recognize conserved microbial patterns. It can be based instead on the ability of the host to sense perturbations in host cells induced by bacterial toxins or 'effectors' that are encoded by pathogenic microorganisms. Such 'effector-triggered immunity' was previously demonstrated mainly in plants, but recent data confirm that animals can also use this strategy. C1 [Stuart, Lynda M.; Paquette, Nicholas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Immunol CCIB, Boston, MA 02114 USA. [Stuart, Lynda M.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Boyer, Laurent] Ctr Mediterraneen Med Mol, C3M, U1065, INSERM, F-06204 Nice, France. RP Stuart, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Immunol CCIB, Boston, MA 02114 USA. EM lstuart@partners.org RI Boyer, laurent/F-8921-2015 OI Boyer, laurent/0000-0002-1375-1706 FU US National Institutes of Health (NIH)/US National Institute of Allergy and Infectious Diseases (NIAID) through the New England Regional Center of Excellence (NERCE) [U54 AI057159]; Ligue Nationale Contre le Cancer; INSERM; Fondation Infectiopole Sud; Fondation ARC pour la Recherche sur le Cancer [ARC SFI 20111203659, ARC SFI 20121205382]; NIH/NIAID FX The authors would like to thank E. Lemichez, F. Ausubel, A. Lacy-Hulbert and J. Irazoqui for their helpful discussion and critical reading of the manuscript. N.P. was supported by the US National Institutes of Health (NIH)/US National Institute of Allergy and Infectious Diseases (NIAID) through the New England Regional Center of Excellence (NERCE) (U54 AI057159); L.B. was supported by Ligue Nationale Contre le Cancer, by institutional funding from INSERM and by grants from Fondation Infectiopole Sud and Fondation ARC pour la Recherche sur le Cancer (ARC SFI 20111203659 and ARC SFI 20121205382); and L.M.S. was supported by grants from NIH/NIAID. NR 58 TC 60 Z9 61 U1 6 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD MAR PY 2013 VL 13 IS 3 BP 199 EP 206 DI 10.1038/nri3398 PG 8 WC Immunology SC Immunology GA 112TJ UT WOS:000316616100012 PM 23411798 ER PT J AU Chowdhury, D Choi, YE Brault, ME AF Chowdhury, Dipanjan Choi, Young Eun Brault, Marie Eve TI DNA DAMAGE - OPINION Charity begins at home: non-coding RNA functions in DNA repair SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAK; MICRORNA BINDING-SITES; TUMOR-SUPPRESSOR; HOMOLOGOUS RECOMBINATION; ULTRACONSERVED REGIONS; BRCA1 EXPRESSION; PROSTATE-CANCER; DOWN-REGULATION; MESSENGER-RNAS; PATHWAY CHOICE AB During the past decade, evolutionarily conserved microRNAs (miRNAs) have been characterized as regulators of almost every cellular process and signalling pathway. There is now emerging evidence that this new class of regulators also impinges on the DNA damage response (DDR). Both miRNAs and other small non-coding RNAs (ncRNAs) are induced at DNA breaks and mediate the repair process. These intriguing observations raise the possibility that crosstalk between ncRNAs and the DDR might provide a means of efficient and accurate DNA repair and facilitate the maintenance of genomic stability. C1 [Chowdhury, Dipanjan; Choi, Young Eun; Brault, Marie Eve] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02215 USA. RP Chowdhury, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02215 USA. EM dipanjan_chowdhury@dfci.harvard.edu FU National Cancer Institute (NCI) [R01CA142698]; National Institute of Allergy and Infectious Diseases (NIAID) [R01 AI101897-01]; Basic Scholar Grant (ACS); Ann-Fuller Foundation; Dana-Farber Cancer Institute (DFCI); Fonds de la Recherche en Sante du Quebec (FRSQ) FX D.C. is supported by the National Cancer Institute (NCI) (R01CA142698), the National Institute of Allergy and Infectious Diseases (NIAID) (R01 AI101897-01), a Basic Scholar Grant (ACS), the Ann-Fuller Foundation and start-up funds from the Dana-Farber Cancer Institute (DFCI). M.E.B. is supported by a fellowship from the Fonds de la Recherche en Sante du Quebec (FRSQ). The authors apologize to their colleagues whose work could not be discussed owing to space constraints. NR 96 TC 48 Z9 48 U1 1 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD MAR PY 2013 VL 14 IS 3 BP 181 EP 189 DI 10.1038/nrm3523 PG 9 WC Cell Biology SC Cell Biology GA 112FK UT WOS:000316577700013 PM 23385724 ER PT J AU Huckans, M Hutson, L Twamley, E Jak, A Kaye, J Storzbach, D AF Huckans, Marilyn Hutson, Lee Twamley, Elizabeth Jak, Amy Kaye, Jeffrey Storzbach, Daniel TI Efficacy of Cognitive Rehabilitation Therapies for Mild Cognitive Impairment (MCI) in Older Adults: Working Toward a Theoretical Model and Evidence-Based Interventions SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE Mild cognitive impairment; Cognitive rehabilitation therapy; Cognitive training; Systematic review; Neuropsychological; Dementia ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; ALZHEIMERS-DISEASE; RISK-FACTORS; PREDICT CONVERSION; PHARMACOLOGICAL-TREATMENT; CARDIOVASCULAR HEALTH; DEPRESSIVE SYMPTOMS; MEDITERRANEAN DIET; PHYSICAL-ACTIVITY AB To evaluate the efficacy of cognitive rehabilitation therapies (CRTs) for mild cognitive impairment (MCI). Our review revealed a need for evidence-based treatments for MCI and a lack of a theoretical rehabilitation model to guide the development and evaluation of these interventions. We have thus proposed a theoretical rehabilitation model of MCI that yields key intervention targets-cognitive compromise, functional compromise, neuropsychiatric symptoms, and modifiable risk and protective factors known to be associated with MCI and dementia. Our model additionally defines specific cognitive rehabilitation approaches that may directly or indirectly target key outcomes-restorative cognitive training, compensatory cognitive training, lifestyle interventions, and psychotherapeutic techniques. Fourteen randomized controlled trials met inclusion criteria and were reviewed. Studies markedly varied in terms of intervention approaches and selected outcome measures and were frequently hampered by design limitations. The bulk of the evidence suggested that CRTs can change targeted behaviors in individuals with MCI and that CRTs are associated with improvements in objective cognitive performance, but the pattern of effects on specific cognitive domains was inconsistent across studies. Other important outcomes (i.e., daily functioning, quality of life, neuropsychiatric symptom severity) were infrequently assessed across studies. Few studies evaluated long-term outcomes or the impact of CRTs on conversion rates from MCI to dementia or normal cognition. Overall, results from trials are promising but inconclusive. Additional well-designed and adequately powered trials are warranted and required before CRTs for MCI can be considered evidence-based. C1 [Huckans, Marilyn; Storzbach, Daniel] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Huckans, Marilyn; Hutson, Lee; Storzbach, Daniel] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Huckans, Marilyn; Storzbach, Daniel] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Twamley, Elizabeth] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA. [Twamley, Elizabeth] Univ Calif San Diego, Stein Inst Res Aging, San Diego, CA 92093 USA. [Twamley, Elizabeth] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA 92161 USA. [Jak, Amy] VA San Diego Healthcare Syst, Dept Psychol Serv, San Diego, CA 92161 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Dept Neurol, Portland, OR 97239 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97239 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol ORATECH, Portland, OR 97239 USA. [Huckans, Marilyn] Portland VA Med Ctr MHN, Portland, OR 97239 USA. RP Huckans, M (reprint author), Portland VA Med Ctr MHN, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM marilyn.huckans@va.gov OI Kaye, Jeffrey/0000-0002-9971-3478 FU VA Merit Review awards; National Institute on Drug Abuse [2P50DA018165-06A1]; National Institute on Aging [P30AG08017, P30AG024978] FX This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center, Portland, Oregon and Oregon Health & Science University, Portland Oregon. This work is in part supported by VA Merit Review awards to DS and JK, a grant from the National Institute on Drug Abuse to MH (2P50DA018165-06A1), and grants from the National Institute on Aging to JK (P30AG08017; P30AG024978). All authors read and approved the final contents of the manuscript. NR 84 TC 40 Z9 40 U1 6 U2 57 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD MAR PY 2013 VL 23 IS 1 SI SI BP 63 EP 80 DI 10.1007/s11065-013-9230-9 PG 18 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 107MR UT WOS:000316222200005 PM 23471631 ER PT J AU De Castro, DK Fay, A Wladis, EJ Nguyen, J Osaki, T Metson, R Curry, W AF De Castro, Dawn K. Fay, Aaron Wladis, Edward J. Nguyen, John Osaki, Tammy Metson, Ralph Curry, William TI Self-Irrigating Piezoelectric Device in Orbital Surgery SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ULTRASONIC BONE REMOVAL; TECHNICAL NOTE; CRANIOFACIAL SURGERY; DECOMPRESSION; OSTEOTOMIES; PIEZOSURGERY; NERVE AB Purpose: Orbital osteotomy risks injury to the eyeball and orbit soft tissues. Used extensively in oral and maxillofacial surgery, piezoelectric technology offers a greater margin of safety than traditional bone cutting instruments. The authors describe the novel use of this system in a variety of orbital surgeries. Methods: This interventional case series was performed in accordance with institutional review board regulations. The medical records of all patients who had undergone orbital surgery using the piezoelectric blade at 3 institutions were reviewed. Indication for surgery, gender, age, duration of follow up, intraoperative complications, surgical result, and postoperative course was recorded. Results: Sixteen patients underwent surgery on 18 orbits using the piezoelectric system between August 2011 and June 2012. Surgeries performed included orbital decompression (8), lateral orbitotomy ( 5), cranio-orbitotomy ( 4), and external dacryocystorhinostomy ( 1). Eight were female and 8 were male patients. Mean age was 55 years old ( standard deviation 15 years). Mean follow up was 82 days. The osteotomy created by the blade was narrow and smooth in every case. The surgeons uniformly appreciated the precision and safety of the instrument compared with traditional electric saw blades. There were no soft tissue lacerations or intraoperative complications and reconstructions were uniformly uneventful. Postoperative healing was rapid with no unexpected inflammation, and no palpable bony defects were appreciated in the reconstructed cases. Conclusions: Because it does not cut soft tissue and cuts a narrow trough, the self-irrigating piezoelectric saw blade appears safer and more precise than traditional electric saw blades in and around the orbit. (Ophthal Plast Reconstr Surg 2013;29:118-122) C1 [De Castro, Dawn K.; Fay, Aaron; Osaki, Tammy] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [De Castro, Dawn K.; Fay, Aaron; Osaki, Tammy] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Wladis, Edward J.] Albany Med Coll, Dept Ophthalmol, Albany, NY 12208 USA. [Nguyen, John] W Virginia Univ, Dept Ophthalmol, Morgantown, WV 26506 USA. [Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Curry, William] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Fay, A (reprint author), Mass Eye & Ear, 243 Charles St, Boston, MA 02114 USA. EM Aaron_fay@meei.harvard.edu RI Osaki, Tammy /G-1539-2016; Menezes, Isabel/D-9281-2012 NR 36 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2013 VL 29 IS 2 BP 118 EP 122 DI 10.1097/IOP.0b013e31827f59d4 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 105HN UT WOS:000316057400023 PM 23328785 ER PT J AU Osaki, TH Fay, A Mehta, M Nallasamy, N Waner, M De Castro, DK AF Osaki, Tammy H. Fay, Aaron Mehta, Manisha Nallasamy, Nambi Waner, Milton De Castro, Dawn K. TI Orbital Development as a Function of Age in Indigenous North American Skeletons SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID COMPUTED-TOMOGRAPHY; GROWTH; VOLUME; SURVIVORS; TRENDS; ADULT AB Purpose: Infants with orbital hemangiomas and vascular malformations often develop expanded orbits or regional hyperostosis. Treatment in these cases depends, in part, on the stage of orbital development at the time of intervention; yet, orbital development with respect to age is not well-known. The authors sought to determine the rate of orbital development and the age of orbital maturation in a single ethnic population. Methods: Skeletons recovered in North America and housed at the Peabody Museum of Archaeology and Ethnology, Harvard University, were inspected. The age of specimen was determined by dentition. Orbital volume was measured using 1-mm glass beads and a graduated cylinder. Linear measurements were taken with calipers and paper rulers. The measurements were plotted against age, and statistical analysis was performed. Relevant literature was reviewed. Results: Of the hundreds of skeletons examined, 42 were sufficiently intact for orbital measurement. The specimens represented a period of up to 1000 years. Thirty-two were pediatric (defined prenatal to 18 years) and 10 were adults. Mean adult orbital volume was 26.2 ml. Based on the regression analysis, 60% of adult orbital volume was achieved at 4.35 years, 75% at 9.36 years, and 90% at 17.13 years of age. Linear dimensions progressively increased with age. Conclusions: This largest direct-measure study of pediatric orbital volume suggests that orbital growth continually decelerates from birth until maturity at 22 years. With 50% of orbital growth occurring by 16 months of age, surgeons removing periocular vascular anomalies after that age should consider concurrent skeletal management. (Ophthal Plast Reconstr Surg 2013;29:131-136) C1 [Osaki, Tammy H.; Fay, Aaron; De Castro, Dawn K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Osaki, Tammy H.; Fay, Aaron; De Castro, Dawn K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Osaki, Tammy H.] Fed Univ Sao Paulo UNIFESP, Dept Ophthalmol, Ophthalm Plast Surg Div, Sao Paulo, Brazil. [Mehta, Manisha] Boston Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. [Nallasamy, Nambi] Harvard Univ, Sch Med, Boston, MA USA. [Waner, Milton] St Lukes Roosevelt Hosp, Vasc Birthmark Inst, New York, NY 10025 USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,10th Floor, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu RI Osaki, Tammy /G-1539-2016; Menezes, Isabel/D-9281-2012 NR 43 TC 5 Z9 6 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2013 VL 29 IS 2 BP 131 EP 136 DI 10.1097/IOP.0b013e3182831c49 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 105HN UT WOS:000316057400026 PM 23416385 ER PT J AU Jakobiec, FA Zakka, FR Yoon, MK AF Jakobiec, Frederick A. Zakka, Fouad R. Yoon, Michael K. TI Complex Orbital Angiomyoma With Features of a Lymphangiohemangioma SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID VENOUS ANOMALIES; OPTIC-NERVE; LYMPHATICS; IDENTIFICATION; MALFORMATIONS; LYMPHANGIOMA; OUTFLOW AB A 31-year-old woman developed left frontal headache and retrobulbar pain with exotropia and mild limitation of upgaze without proptosis. Imaging studies disclosed a circumscribed mass measuring 1.5 cm in the greatest diameter. At surgery, the lesion was adherent to the surrounding normal orbital tissues, making for a difficult and dangerous resection. Histopathologically and immunohistochemically, the lesion was a mixed cavernous angiomatous (CD31-positive) and lymphangiomatous (D2-40-postive) tumor with abundant interstitial smooth muscle. Such lesions can present significant surgical challenges due to incomplete pseudoencapsulation. C1 [Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Oculoplast Serv, Boston, MA 02114 USA. [Yoon, Michael K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol,Dept Ophthalmol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 21 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2013 VL 29 IS 2 BP E61 EP E65 DI 10.1097/IOP.0b013e31826b777d PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 105HN UT WOS:000316057400013 PM 23235513 ER PT J AU Westbrook, SD Kirkpatrick, WR Wiederhold, NP Freytes, CO Toro, JJ Patterson, TF Redding, SW AF Westbrook, Steven D. Kirkpatrick, William R. Wiederhold, Nathan P. Freytes, Cesar O. Toro, Juan J. Patterson, Thomas F. Redding, Spencer W. TI Microbiology and epidemiology of oral yeast colonization in hemopoietic progenitor cell transplant recipients SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; FUNGAL-INFECTIONS; SEPSIS SECONDARY; FLUCONAZOLE; MUCOSITIS; CHEMOTHERAPY; PREVENTION; TRIAL AB Objective. We monitored the epidemiology and microbiology of oral yeast colonization in patients undergoing hemopoietic progenitor cell transplantation (HPCT) to examine associations between yeast colonization and oral mucositis. Study Design. One hundred twenty-one consecutive HPCT patients were sampled for oral yeasts prior to fluconazole (FLC) prophylaxis, at transplantation, and weekly until discharge. Clinical oral mucositis screenings were performed triweekly. Results. Yeast colonization was evident at 216 of 510 total visits. Candida albicans and Candida glabrata were the predominant organisms. Eight patients showed elevated minimal inhibitory concentrations to FLC. One patient developed fungal septicemia. Patients with oral mucositis assessment scale scores <20 had higher colonization rates than those with higher scores. Conclusions. FLC is effective in controlling a variety of oral yeasts in HPCT recipients. FLC-resistant yeasts do emerge and can be the source of fungal sepsis. A positive association was not shown between yeast colonization and the presence or severity of oral mucositis. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:354-358) C1 [Westbrook, Steven D.; Redding, Spencer W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Kirkpatrick, William R.; Wiederhold, Nathan P.; Freytes, Cesar O.; Toro, Juan J.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Austin, TX USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Div Pharmacotherapy, Austin, TX 78712 USA. RP Westbrook, SD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, 7703 Floyd Curl Dr,MSC 7914, San Antonio, TX 78229 USA. EM westbrooks@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU Public Health Service from the National Institute of Dental and Craniofacial Research [DE-18096] FX The authors thank Marcos Olivo for his technical assistance with yeast identification and isolation. We are grateful to the Fungus Testing Laboratory of the University of Texas Health Science Center at San Antonio for their assistance in determining the MICs of the yeast isolates. This work was supported in part by Public Health Service Grant DE-18096 from the National Institute of Dental and Craniofacial Research. NR 20 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-4403 J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD MAR PY 2013 VL 115 IS 3 BP 354 EP 358 DI 10.1016/j.oooo.2012.10.012 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 109DJ UT WOS:000316345500022 PM 23312542 ER PT J AU Murinson, BB Gordin, V Flynn, S Driver, LC Gallagher, RM Grabois, M AF Murinson, Beth B. Gordin, Vitaly Flynn, Susie Driver, Larry C. Gallagher, Rollin M. Grabois, Martin CA Amer Acad Pain Med TI Recommendations for a New Curriculum in Pain Medicine for Medical Students: Toward a Career Distinguished by Competence and Compassion SO PAIN MEDICINE LA English DT Article DE Medical Education; Curriculum; AAPM; Medical Student; Learning Objectives ID PHYSICIANS; EDUCATION; EMPATHY; SCHOOLS AB Objective The education of physicians is a fundamental obligation within medicine that must remain closely aligned with clinical care. And although medical education in pain care is essential, the current state of medical education does not meet the needs of physicians, patients, or society. To address this, we convened a committee of pain specialist medical student educators. Methods Tasked with creating systematically developed and valid recommendations for clinical education, we conducted a survey of pain medicine leadership within the American Academy of Pain Medicine (AAPM). The survey was conducted in two waves. We asked AAPM board members to rate 194 previously published pain medicine learning objectives for medical students; 79% of those eligible for participation responded. Results The Top 5 list included the awareness of acute and chronic pain, skillfulness in clinical appraisal, promotion of compassionate practices, displaying empathy toward the patient, and knowledge of terms and definitions for substance abuse. The Top 10 list included the major pharmacological classes as well as skills in examination, communication, prescribing, and interviewing. The Top 20 list included the pain care of cognitively impaired populations, those with comorbid illness, and older adults. With the survey results in consideration, the committee produced a new recommended topic list for curricula in pain medicine. We strongly recommend that adequate resources are devoted to fully integrated medical curricula in pain so that students will learn not only the necessary clinical knowledge but also be prepared to address the professional, personal, and ethical challenges that arise in caring for those with pain. Conclusions We conclude that improved medical education in pain is essential to prepare providers who manifest both competence and compassion toward their patients. C1 [Murinson, Beth B.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Gordin, Vitaly] Penn State Coll Med, Dept Anesthesia, Hershey, PA USA. [Flynn, Susie] Amer Acad Pain Med, Chicago, IL USA. [Driver, Larry C.] UT MD Anderson Canc Ctr, Dept Anesthesiol & Pain Med, Houston, TX USA. [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Dept Pain Med, Philadelphia, PA USA. [Gallagher, Rollin M.] Univ Penn, Ctr Pain Med Res & Policy, Philadelphia, PA 19104 USA. [Grabois, Martin] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Murinson, BB (reprint author), Johns Hopkins Sch Med, Dept Neurol, Ctr Excellence Pain Educ, Meyer 5-119,600 North Wolfe St, Baltimore, MD 21287 USA. EM bb@jhmi.edu OI Murinson, Beth/0000-0003-1543-4322 FU Mayday Fund; Milbank Foundation for Rehabilitation Research; National Institute of Health Pain Consortium; National Institutes of Health FX This work was supported in part by philanthropic funding from the Mayday Fund and the Milbank Foundation for Rehabilitation Research. Dr. Murinson was the recipient of a National Institutes of Health career development award and the director of the Johns Hopkins University Center of Excellence in Pain Education funded by the National Institute of Health Pain Consortium. NR 20 TC 13 Z9 13 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD MAR PY 2013 VL 14 IS 3 BP 345 EP 350 DI 10.1111/pme.12051 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 107IV UT WOS:000316210600011 PM 23387441 ER PT J AU Keel, JC Lau, ME Gulur, P AF Keel, John C. Lau, Mary E. Gulur, Padma TI Spinal Cord Stimulation for Radicular Pain Following Retained Bullet in the Spinal Canal SO PAIN PHYSICIAN LA English DT Article DE Spinal cord stimulation; radicular pain; retained bullet; gunshot wound; spinal canal; spinal injury; lumbar spine ID GUNSHOT WOUNDS AB We are reporting on the implantation of a spinal cord stimulator to treat intractable radicular pain following a retained bullet fragment in the spinal canal. Such retained fragments are associated with risks including pain, neurological deficit, infection, toxic effects, and migration. Our patient was a young man with radicular pain and history of a gunshot entering the abdomen. Computed tomography of the spine had revealed a nearly complete bullet in the right paracentral canal at L4, partially extending into the lateral recess. He presented 17 months after his injury with gradually worsening pain and parasthesias radiating from the back to the whole right leg and foot. There was no weakness. As the patient had failed conservative therapy, procedural options were considered. In this case, the potential benefits of epidural steroid injection by any approach might not have outweighed risks of infection, related to foreign body and local steroid, or possible migration due to mechanical forces during injection. As he may well need repeated epidural steroid injections to manage his pain, this increases his risk for infection. A percutaneous trial spinal cord stimulation lead was placed, with epidural entry well away from the bullet. After good results, a permanent system was implanted. There was no evidence of infection or migration, and excellent pain relief was achieved. Bullets and other foreign bodies retained in the spinal canal can cause progressive neurologic symptoms through reactive tissue formation and compression. Spinal cord stimulation can relieve radicular pain while avoiding risks associated with altering the location of the offending foreign body. C1 [Gulur, Padma] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Keel, John C.; Lau, Mary E.; Gulur, Padma] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keel, John C.; Gulur, Padma] Harvard Univ, Sch Med, Boston, MA USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 15 Parkman St,WACC330, Boston, MA 02114 USA. EM pgulur@yahoo.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAR-APR PY 2013 VL 16 IS 2 BP E103 EP E106 PG 4 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 109JI UT WOS:000316362700006 PM 23511684 ER PT J AU Fu, Y Cheetham, T Bourn, D Orwoll, E Cohen, DM AF Fu, Yi Cheetham, Tim Bourn, David Orwoll, Eric Cohen, David M. TI Functional polymorphisms affecting the clinically important arginine-137 residue of AVPR2 do not influence serum sodium concentration at the population level SO PHYSIOLOGICAL GENOMICS LA English DT Article DE osmoregulation; arginine vasopressin; hyponatremia; hypernatremia ID NEPHROGENIC DIABETES-INSIPIDUS; CORONARY-HEART-DISEASE; V2 RECEPTOR MUTANTS; VASOPRESSIN RECEPTOR; INAPPROPRIATE ANTIDIURESIS; OSTEOPOROTIC FRACTURES; HYPONATREMIA; RESCUE; MEN; HOPEWELL AB Fu Y, Cheetham T, Bourn D, Orwoll E, Cohen DM. Functional polymorphisms affecting the clinically important arginine-137 residue of AVPR2 do not influence serum sodium concentration at the population level. Physiol Genomics 45: 210-216, 2013. First published January 29, 2013; doi:10.1152/physiolgenomics.00161.2012.-The protein product of the AVPR2 gene, coding for the arginine vasopressin receptor type 2, is essential for vasopressin-dependent concentration of the urine. The arginine residue at position 137 in the protein product of this gene is uniquely pivotal for function. The R137H mutant inactivates the receptor conferring congenital nephrogenic diabetes insipidus, whereas activating mutations at this same residue (i.e., R137C and R137L) confer pathological water retention in the nephrogenic syndrome of inappropriate antidiuresis. These mutations were discovered in human subjects with conspicuous phenotypes in clinical water balance. Prevalence of these polymorphisms among asymptomatic individuals has not been assessed, nor has their contribution to broad interindividual variation in serum sodium concentration; no data addressing minor allele frequency are available. We genotyped two large cohorts using a validated high-throughput Pyrosequencing-based assay that we designed to capture the totality of pathological variation at this important residue. In the Osteoporotic Fractures in Men (MrOS) Study, all participants were male (i.e., hemizygous for AVPR2 gene on the X-chromosome), and participants were oversampled at the extremes of the population distribution for serum sodium concentration. In the Offspring Cohort of the Framingham Heart Study, male and female participants were genotyped. No pathological variants affecting R137 were detected among the 5,142 AVPR2 alleles successfully genotyped. Even at the population extremes of serum sodium distribution, we estimate minor allele frequency < 0.06%. We conclude that these disease-associated variants are exceedingly uncommon and do not contribute broadly to interindividual variability in serum sodium concentration or to its heritability. C1 [Fu, Yi; Cohen, David M.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. [Orwoll, Eric] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol & Metab, Portland, OR 97239 USA. [Fu, Yi; Cohen, David M.] Portland VA Med Ctr, Portland, OR USA. [Cheetham, Tim] Royal Victoria Infirm, Dept Paediat Endocrinol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Bourn, David] Inst Genet, Mol Genet Lab, Newcastle Upon Tyne, Tyne & Wear, England. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Mailcode PP262, Portland, OR 97239 USA. EM cohend@ohsu.edu OI Orwoll, Eric/0000-0002-8520-7355 FU National Institutes of Health (NIH); Department of Veterans Affairs; American Heart Association; NIH; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA); National Center for Research Resources; NIH Roadmap for Medical Research [U01 AR-45580, U01 AR-45614, U01 AR-45632, U01 AR-45647, U01 AR-45654, U01 AR-45583, U01 AG-18197, U01-AG-027810, UL1 RR-024140]; American Diabetes Association [1-04-JF-46]; NIAMS [R01-AR-051124]; National Heart, Lung, and Blood Institute's (NHLBI's) Framingham Heart Study [N01-HC-25195]; NHLBI; Boston University FX This work is supported by grants from the National Institutes of Health (NIH), the Department of Veterans Affairs, and the American Heart Association. The MrOS Study is supported by NIH funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources, and NIH Roadmap for Medical Research under the following grant numbers: U01 AR-45580, U01 AR-45614, U01 AR-45632, U01 AR-45647, U01 AR-45654, U01 AR-45583, U01 AG-18197, U01-AG-027810, and UL1 RR-024140. Support for MrOS was also provided by the American Diabetes Association (1-04-JF-46). The NIAMS provides funding for the MrOS ancillary study "Replication of candidate gene associations and bone strength phenotype in MrOS" under the grant number R01-AR-051124.; A portion of this work was supported by the National Heart, Lung, and Blood Institute's (NHLBI's) Framingham Heart Study (contract no. N01-HC-25195). The Framingham Heart Study is conducted and supported by the NHLBI in collaboration with Boston University. This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. NR 36 TC 4 Z9 4 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAR PY 2013 VL 45 IS 6 BP 210 EP 216 DI 10.1152/physiolgenomics.00161.2012 PG 7 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 109EF UT WOS:000316348100002 PM 23362144 ER PT J AU Kim, W Charchian, B Chang, EY Liang, LJ Dumas, AJ Perez, M Siebens, HC Kim, HS AF Kim, Woojae Charchian, Beny Chang, Eric Y. Liang, Li-Jung Dumas, Armen J. Perez, Mario Siebens, Hilary C. Kim, Hyung S. TI Strengthening Information Capture in Rehabilitation Discharge Summaries: An Application of the Siebens Domain Management Model SO PM&R LA English DT Article ID BIOPSYCHOSOCIAL MODEL; MEDICAL RECORDS; CARE; PATTERNS; PATIENT; TEACH; GUIDE AB Objective: To increase relevant information capture in inpatient rehabilitation discharge summaries. Design: In July 2008, the Siebens Domain Management Model (SDMM) was incorporated into discharge summaries. This model organizes patients' health-related issues into 4 domains: I. Medical/Surgical Issues, II. Mental Status/Emotions/Coping, III. Physical Function, and IV. Living Environment ((c) Hilary C. Siebens MD 2005). Discharge summary content was measured through retrospective chart review. Setting: An inpatient rehabilitation unit affiliated with a physical medicine and rehabilitation residency program. Participants: Forty cases with discharge summaries: 20 traditional reports (historic controls) and 20 SDMM reports after model introduction randomly chosen from residents' final inpatient rotation week. Methods: A documentation review form included 36 items that covered the 4 SDMM domains and assessed item presence in reports. The Global score and 4 Domain scores per each patient report were calculated to reflect the percentage of items present in the entire report and each domain, respectively. Descriptive statistics for these scores were generated and compared between traditional and SDMM reports by using a 2-group t-test. Main Outcome Measurements: Global scores and Domain scores. Results: Global scores increased from 34% to 53% of items present in traditional versus SDMM reports respectively (P < .001); Domain Scores also increased in domains 1(81% to 92%, P = .047), II (9% to 47%, P < .001), III (25% to 34%, P = .062), and IV (11% to 33%, P < .001). Conclusion: Traditional rehabilitation discharge summaries lacked information relevant to rehabilitation care. Information capture and total relevant report content increased significantly after SDMM integration into reports. PM R 2013;5:182-188 C1 [Kim, Woojae] Valley Orthoped Inst, Palmdale, CA USA. [Charchian, Beny] Orthohealing Ctr, Los Angeles, CA USA. [Chang, Eric Y.] Univ Calif Irvine, Sch Med, Div Pain Med, Dept Anesthesiol & Perioperat Care, Irvine, CA 92717 USA. [Chang, Eric Y.] Univ Calif Irvine, Sch Med, Dept Phys Med & Rehabil, Irvine, CA 92717 USA. [Liang, Li-Jung; Dumas, Armen J.; Perez, Mario; Kim, Hyung S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Dumas, Armen J.; Perez, Mario; Kim, Hyung S.] VA Greater Los Angeles Healthcare Syst, Phys Med & Rehabil Serv, Los Angeles, CA USA. [Siebens, Hilary C.] Siebens Patient Care Commun, Seal Beach, CA USA. RP Kim, HS (reprint author), 11301 Wilshire Blvd MC117, Los Angeles, CA 90073 USA. EM Hyung.Kim@va.gov FU Department of Veterans Affairs, Greater Los Angeles FX We thank Harriet U. Aronow, PhD, Carol Stein, MA, OTR/L, Crystal Barker, MSN, RN-BC, PHN, CRRN, Milena Zirovich, MD, Stephen Figoni, PhD, and Antonia E. Scremin, MD, for their contributions to this project, and the Department of Veterans Affairs, Greater Los Angeles for funding statistical support. NR 38 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2013 VL 5 IS 3 BP 182 EP 188 DI 10.1016/j.pmrj.2013.01.003 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 110HN UT WOS:000316433300004 PM 23481328 ER PT J AU Suri, P Dharamsi, AS Gaviola, G Isaac, Z AF Suri, Pradeep Dharamsi, Aisha S. Gaviola, Glenn Isaac, Zacharia TI Are Facet Joint Bone Marrow Lesions and Other Facet Joint Features Associated With Low Back Pain? A Pilot Study SO PM&R LA English DT Article ID HIGH-INTENSITY ZONE; KNEE OSTEOARTHRITIS; LUMBAR SPINE; DISCOGRAPHY CORRELATION; CLINICAL-FEATURES; EDEMA; PREVALENCE; MRI; SYNOVITIS; DISK AB Objective: To determine the frequency of facet joint (FJ) bone marrow lesions, high FJ periarticular signal intensity, and FJ effusions in a convenience sample of patients with axial low back pain (LBP). Design: A cross-sectional pilot study with-retrospective data collection. Setting: Outpatient spine clinics. Patients: Sixty-four adults with axial LBP scheduled to receive an FJ intra-articular corticosteroid injection. Methods: Clinical data were abstracted from the medical record by 1 physician, who was blinded to results of the magnetic resonance imaging evaluations. A musculoskeletal radiologist blinded to clinical information performed standardized assessments of the L1-S1 spinal levels for FJ bone marrow lesions, effusions, and high periarticular signal intensity on lumbar magnetic resonance imaging, including short tau inversion recovery sequences. We calculated the frequency of these FJ features and used generalized estimating equations to examine side-specific associations between the location of FJ features and the side on which LBP was experienced. Results: The sample included 64 participants with a mean (standard deviation) age of 59.9 +/- 14.5 years. FJ bone marrow lesions were present in 64.1%, effusions in 70.3%, and high periarticular signal intensity in 65.6% of participants. All the features were most common at the L4-L5 level. These FJ features showed significant associations with the side on which LBP was experienced or statistical trends toward an association, with or without adjustment for age, gender, and body mass index. The strongest side-specific associations were seen for the number of bone marrow lesions (odds ratio [OR] 1.60 [95% confidence interval (CI),1.05-2.43]), any FJ effusion (OR 2.23 [95% CI, 1.02-4.85]), and the number of joints with -high periarticular signal intensity (OR 1.75 [95% CI, 1.16-2.63]). Conclusions: FJ bone marrow lesions, effusions, and high periarticular signal intensity were common in this sample of patients with axial LBP and substantially more frequent than in prior reports from unselected samples of patients with or without radicular pain. These FJ features demonstrate side-specific associations with LBP. Further study of associations between these FJ features and LBP are warranted. PM R2013;5:194-200 C1 [Suri, Pradeep] VA Boston Healthcare Syst, Div Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep; Dharamsi, Aisha S.; Isaac, Zacharia] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep; Dharamsi, Aisha S.; Isaac, Zacharia] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep] New England Baptist Hosp, Dept Orthoped, Boston, MA USA. [Suri, Pradeep] VA Puget Sound Healthcare Syst, Div Rehabil Care Serv, Seattle, WA 98108 USA. [Gaviola, Glenn] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Gaviola, Glenn] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Isaac, Zacharia] Brigham & Womens Hosp, Dept Phys Med & Rehabil, Boston, MA 02115 USA. RP Suri, P (reprint author), VA Boston Healthcare Syst, Div Phys Med & Rehabil, Boston, MA USA. EM pradeep.suri@va.gov FU NICHD NIH HHS [K12 HD 01097] NR 41 TC 5 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2013 VL 5 IS 3 BP 194 EP 200 DI 10.1016/j.pmrj.2012.09.002 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 110HN UT WOS:000316433300006 PM 23122893 ER PT J AU Evans, CT St Andre, JR Pape, TLB Steiner, ML Stroupe, KT Hogan, TP Weaver, FM Smith, BM AF Evans, Charlesnika T. St Andre, Justin R. Pape, Theresa L. -B. Steiner, Monica L. Stroupe, Kevin T. Hogan, Timothy P. Weaver, Frances M. Smith, Bridget M. TI An Evaluation of the Veterans Affairs Traumatic Brain Injury Screening Process Among Operation Enduring Freedom and/or Operation Iraqi Freedom Veterans SO PM&R LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; AFGHANISTAN; SYMPTOMS; HEALTH; CARE AB Objective: To describe the early results of the U.S. Department of Veterans Affairs (VA) screening program for traumatic brain injury (TBI) and to identify patient and facility characteristics associated with receiving a TBI screen and results of the screening. Design: National retrdspective cohort study. Setting: VA Medical facilities. Patients: A total of 170,681 Operation Enduring Freedom and/or Operation Iraqi Freedom (OEF/OIF) Veterans who sought care at VA medical facilities from April 2007 to September 30, 2008. Methods: Data were abstracted from VA administrative and operational databases, including patient demographics, facility characteristics, and outcomes. Main Outcome Measurements: The main outcomes were receipt of and results of the TBI screen. Results: The majority of veterans eligible received the TBI screen (91.6%). Screening rates varied by patient and facility characteristics. In all, 25% of screened veterans had probable TBI exposure, in which the majority. of the exposures were blasts (85.0%). The rate of a positive TBI screen was 20.5% for the screened cohort. Male gender, service in the army, multiple deployments, and mental health diagnoses in the previous year were associated with a positive screen. Conclusions: TBI screening rates are high in VA; concomitant mental health diagnoses were highly prevalent in individuals with positive TBI screens. These data indicate that there will be a significant need for long-term health care services for veterans with TBI symptomatology. PM R 2013;5:210-220 C1 [Evans, Charlesnika T.] Edward Hines Jr Vet Affairs VA Hosp, Dept VA, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Evans, Charlesnika T.] Spinal Cord Injury Qual Enhancement Res Initiat S, Dept VA, Hines, IL USA. [Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. [St Andre, Justin R.; Pape, Theresa L. -B.; Stroupe, Kevin T.; Hogan, Timothy P.; Weaver, Frances M.; Smith, Bridget M.] Hines VA Hosp, Ctr Management Complex Chron Care, Dept VA, Hines, IL USA. [St Andre, Justin R.; Hogan, Timothy P.; Weaver, Frances M.; Smith, Bridget M.] SCI QUERI, Dept VA, Hines, IL USA. [St Andre, Justin R.] Hlth Res & Educ Trust, Chicago, IL USA. [Pape, Theresa L. -B.; Steiner, Monica L.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept VA, Hines, IL 60141 USA. [Pape, Theresa L. -B.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Stroupe, Kevin T.; Weaver, Frances M.; Smith, Bridget M.] Loyola Univ Chicago, Stritch Sch Med, Program Hlth Serv Res, Maywood, IL USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, eHlth QUERI, Natl eHlth QUERI Coordinating Ctr, Bedford, MA USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA USA. RP Evans, CT (reprint author), Edward Hines Jr Vet Affairs VA Hosp, Dept VA, Ctr Management Complex Chron Care, 5000 S 5th Ave, Hines, IL 60141 USA. EM Charlesnika.Evans@va.gov OI Pape, Theresa/0000-0001-7738-5963 NR 21 TC 12 Z9 12 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2013 VL 5 IS 3 BP 210 EP 220 DI 10.1016/j.pmrj.2012.12.004 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 110HN UT WOS:000316433300008 PM 23375630 ER PT J AU Kang, JX AF Kang, Jing X. TI Dr. Alexander Leaf, an exemplary physician-scientist and a great man Obituary SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Biographical-Item C1 [Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. EM kang.jing@mgh.harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAR PY 2013 VL 88 IS 3 BP 197 EP 199 DI 10.1016/j.plefa.2013.01.008 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 110EP UT WOS:000316425700001 PM 23615572 ER PT J AU Timpano, KR Broman-Fulks, JJ Glaesmer, H Exner, C Rief, W Olatunji, BO Keough, ME Riccardi, CJ Brahler, E Wilhelm, S Schmidt, NB AF Timpano, Kiara R. Broman-Fulks, Joshua J. Glaesmer, Heide Exner, Cornelia Rief, Winfried Olatunji, Bunmi O. Keough, Meghan E. Riccardi, Christina J. Braehler, Elmar Wilhelm, Sabine Schmidt, Norman B. TI A Taxometric Exploration of the Latent Structure of Hoarding SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE hoarding; taxometrics; dimensional latent structure ID SYMPTOM DIMENSIONS; COGNITIVE ASPECTS; DISORDER; PSYCHOPATHOLOGY; CLASSIFICATION; DISTRIBUTIONS; INVENTORY; BURDEN; TESTS; MODEL AB Despite controversy regarding the classification and diagnostic status of hoarding disorder, there remains a paucity of research on the nosology of hoarding that is likely to inform the classification debate. The present investigation examined the latent structure of hoarding in three, large independent samples. Data for three well-validated measures of hoarding were subjected to taxometric procedures, including MAXimum EIGenvalue, Mean Above Minus Below A Cut, and Latent-Mode factor. Two symptom measures, one of which closely mirrors the proposed diagnostic criteria for hoarding disorder, and a measure of hoarding beliefs were analyzed. Sample 1 (n = 2,501) was representative of the general German population, while Samples 2 (n = 1,149) and 3 (n = 500) consisted of unselected undergraduate students. Findings across all three samples and taxometric procedures provided converging evidence that hoarding is best conceptualized as a dimensional construct, present in varying degrees in all individuals. Results have implications across research and treatment domains, particularly with respect to assessment approaches, treatment response determination, and policy decisions. These findings underscore the need for further investigations on the nosology of hoarding, to help validate this construct as we move forward with respect to our research and treatment efforts, as well as the potential inclusion of hoarding disorder in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2012). C1 [Timpano, Kiara R.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Broman-Fulks, Joshua J.] Appalachian State Univ, Dept Psychol, Boone, NC 28608 USA. [Glaesmer, Heide; Braehler, Elmar] Univ Leipzig, Abt Med Psychol & Med Soziol, D-04109 Leipzig, Germany. [Exner, Cornelia] Univ Leipzig, Dept Clin Psychol, D-04109 Leipzig, Germany. [Rief, Winfried] Univ Marburg, Dept Psychol, D-35032 Marburg, Germany. [Olatunji, Bunmi O.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37235 USA. [Keough, Meghan E.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Riccardi, Christina J.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Schmidt, Norman B.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Timpano, KR (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd, Coral Gables, FL 33146 USA. EM kiaratimpano@gmail.com OI Exner, Cornelia/0000-0001-5904-6511; Timpano, Kiara/0000-0002-0665-8722 NR 41 TC 13 Z9 13 U1 1 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 2013 VL 25 IS 1 BP 194 EP 203 DI 10.1037/a0029966 PG 10 WC Psychology, Clinical SC Psychology GA 104EH UT WOS:000315974000018 PM 22984803 ER PT J AU Blais, MA Malone, JC Stein, MB Slavin-Mulford, J O'Keefe, SM Renna, M Sinclair, SJ AF Blais, Mark A. Malone, Johanna C. Stein, Michelle B. Slavin-Mulford, Jenelle O'Keefe, Sheila M. Renna, Megan Sinclair, Samuel J. TI Treatment as Usual (TAU) for Depression: A Comparison of Psychotherapy, Pharmacotherapy, and Combined Treatment at a Large Academic Medical Center SO PSYCHOTHERAPY LA English DT Article DE outcomes monitoring; depression; psychotherapy; pharmacotherapy; treatment as usual ID MENTAL-HEALTH TREATMENT; STAR-ASTERISK-D; CLINICAL-SIGNIFICANCE; MAJOR DEPRESSION; METAANALYSIS; CARE; DISORDER; OUTCOMES; REPLICATION; THERAPIES AB Depression is among the most prevalent and burdensome psychiatric disorders in the United States (Kessler et al., Achieves of General Psychiatry 62:617-627, 2005). There is substantial empirical support regarding efficacy of pharmacotherapy, psychotherapy, and combined treatment (both pharmacotherapy and psychotherapy) for treating depression. However, far less is known about the effectiveness of these treatments for real-world patients treated within routine clinical care settings (Cahill et al., The British Journal of Clinical Psychology 49:421-453, 2010). This study seeks to explore the effectiveness of treatment as usual (TAU) for depression in a large cohort of psychiatric outpatients receiving psychotherapy, pharmacotherapy, or combined treatment within an academic medical center. Initial and follow-up self-report assessments were analyzed for 1,322 patients receiving treatment for depression. Using these data, we determined treatment effect sizes, rates of reliable improvement (and deterioration), and rates of clinically significant improvement for psychotherapy, pharmacotherapy, and combined care. On average, all treatments produced significant improvement with effect sizes surpassing our no-treatment benchmark. No significant between-group (treatment) differences in self-report outcomes were found. The rates of reliable change were similar for all treatment groups consistent with past research. The present findings support the effectiveness of psychotherapy, pharmacotherapy, and combined treatment as routinely provided within a large academic medical center for the treatment of real-world patients suffering with depression. C1 [Blais, Mark A.; Malone, Johanna C.; Stein, Michelle B.; O'Keefe, Sheila M.; Renna, Megan; Sinclair, Samuel J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blais, Mark A.; Malone, Johanna C.; Stein, Michelle B.; O'Keefe, Sheila M.; Renna, Megan; Sinclair, Samuel J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Slavin-Mulford, Jenelle] Georgia Regents Univ, Dept Psychol, Augusta, GA USA. RP Blais, MA (reprint author), Psychol Assessment Ctr, 1 Bowdoin Sq,702, Boston, MA 02114 USA. EM Mblais@partners.org NR 45 TC 6 Z9 6 U1 6 U2 40 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD MAR PY 2013 VL 50 IS 1 SI SI BP 110 EP 118 DI 10.1037/a0031385 PG 9 WC Psychology, Clinical SC Psychology GA 106PA UT WOS:000316155800015 PM 23505987 ER PT J AU Weinstein, S Osei-Bonsu, S Aslam, R Yee, J AF Weinstein, Stefanie Osei-Bonsu, Samuel Aslam, Rizwan Yee, Judy TI Multidetector CT of the Postoperative Colon: Review of Normal Appearances and Common Complications SO RADIOGRAPHICS LA English DT Article ID POUCH-ANAL ANASTOMOSIS; COMPUTED-TOMOGRAPHY; ANTERIOR RESECTION; RECTAL-CANCER; ABDOMINOPERINEAL RESECTION; ABDOMINAL COMPLICATIONS; DIVERSION COLITIS; COLORECTAL-CANCER; HARTMANNS POUCH; BARIUM ENEMA AB If not properly recognized, the normal postoperative appearance of the pelvis following colorectal surgery can be misinterpreted as disease, including infection or recurrent tumor. However, multidetector computed tomography (CT) with the supplemental use of multiplanar reformation clearly demonstrates the expected postoperative anatomic changes in this setting. The high-resolution images achievable with multidetector CT enable the radiologist to play an important role in the postoperative assessment of patients following colon surgery. Whenever possible, the radiologist should be aware of the specific indication for the study, the type of surgery that was performed (ranging from segmental bowel excision to more extensive radical resection), and what anastomoses were created. This knowledge, as well as familiarity with the normal multidetector CT appearances of various postoperative complications, is critical for prompt diagnosis and appropriate management of these complications and for better differentiation of complications from normal findings. (C)RSNA, 2013 center dot radiographics.rsna.org C1 [Weinstein, Stefanie; Osei-Bonsu, Samuel; Aslam, Rizwan; Yee, Judy] UCSF Med Ctr, Dept Radiol, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Weinstein, S (reprint author), UCSF Med Ctr, Dept Radiol, San Francisco VA Med Ctr, 4150 Clement St 114, San Francisco, CA 94121 USA. EM Stefanie.Weinstein@ucsf.edu NR 54 TC 7 Z9 7 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2013 VL 33 IS 2 BP 515 EP 532 DI 10.1148/rg.332125723 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 104MU UT WOS:000315998700016 PM 23479710 ER PT J AU Soehnlein, O Swirski, FK AF Soehnlein, Oliver Swirski, Filip K. TI Hypercholesterolemia links hematopoiesis with atherosclerosis SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review DE hypercholesterolemia; atherosclerosis; hematopoietic stem and progenitor cells; monocytes; neutrophils ID LIVER-X-RECEPTOR; ACUTE CORONARY SYNDROMES; STEM-CELL PROLIFERATION; BONE-MARROW; LXR-ALPHA; ACCELERATES ATHEROSCLEROSIS; PROGENITOR CELLS; DEFICIENT MICE; HEART-DISEASE; REDUCES ATHEROSCLEROSIS AB Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to the necrotic core of lesions. Lipids and leukocytes also interact in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol-sensing pathways control the proliferation of hematopoietic stem-cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation, and propose several strategies that could target this axis for the treatment of cardiovascular disease. C1 [Soehnlein, Oliver] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. [Soehnlein, Oliver] Univ Munich, Inst Cardiovasc Prevent, Munich, Germany. [Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA USA. RP Soehnlein, O (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. EM oliver.soehnlein@gmail.com FU German Research Foundation [SO876/3-1, FOR809, SFB914 TPB08]; German-Israeli Foundation; FoFoLe Program within the Medical Faculty of the LMU Munich; Else Kroner Fresenius Stiftung; NWO; National Institutes of Health [R01 HL095612] FX O.S. was supported by the German Research Foundation (SO876/3-1, FOR809, SFB914 TPB08), the German-Israeli Foundation, the FoFoLe Program within the Medical Faculty of the LMU Munich, the Else Kroner Fresenius Stiftung, and the NWO. F.K.S. was supported by the National Institutes of Health (R01 HL095612). NR 99 TC 22 Z9 22 U1 0 U2 11 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 MAR PY 2013 VL 24 IS 3 BP 129 EP 136 DI 10.1016/j.tem.2012.10.008 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109LS UT WOS:000316370700003 PM 23228326 ER PT J AU Habener, JF Stanojevic, V AF Habener, Joel F. Stanojevic, Violeta TI Alpha cells come of age SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review DE transdifferentiation; beta cell regeneration; alpha cell hyperplasia; GLP-1-derived peptides ID GLUCAGON-LIKE PEPTIDE-1; PANCREATIC BETA-CELLS; RECEPTOR KNOCKOUT MICE; EPITHELIAL-MESENCHYMAL TRANSITIONS; TYPE-2 DIABETES-MELLITUS; ADULT-MOUSE PANCREAS; GLP-1 9-36 AMIDE; ENDOCRINE PANCREAS; PROGENITOR CELLS; INSULIN SENSITIVITY AB The alpha cells that coinhabit the islets with the insulin-producing beta cells have recently captured the attention of diabetes researchers because of new breakthrough findings highlighting the importance of these cells in the maintenance of beta cell health and functions. In normal physiological conditions alpha cells produce glucagon but in conditions of beta cell injury they also produce glucagon-like peptide-1 (GLP-1), a growth and survival factor for beta cells. In this review we consider these new findings on the functions of alpha cells. Alpha cells remain somewhat enigmatic inasmuch as they now appear to be important in the maintenance of the health of beta cells, but their production of glucagon promotes diabetes. This circumstance prompts an examination of approaches to coax alpha cells to produce GLP-1 instead of glucagon. C1 [Habener, Joel F.; Stanojevic, Violeta] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. EM jhabener@partners.org FU Juvenile Diabetes Research Foundation; American Diabetes Association; Novo Nordisk; Merck Company FX We thank Vishal Saxena and Rebecca Laudone for helpful suggestions for revising the manuscript. Supported in part by grants from the Juvenile Diabetes Research Foundation, the American Diabetes Association, Novo Nordisk, and Merck & Company. NR 137 TC 25 Z9 26 U1 1 U2 16 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 MAR PY 2013 VL 24 IS 3 BP 153 EP 163 DI 10.1016/j.tem.2012.10.009 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109LS UT WOS:000316370700006 PM 23260869 ER PT J AU Brazeau, NF Harvey, HB Pinto, EG Deipolyi, A Hesketh, RL Oklu, R AF Brazeau, Nicholas F. Harvey, Harlan B. Pinto, Erique G. Deipolyi, Amy Hesketh, Richard L. Oklu, Rahmi TI May-Thurner syndrome: diagnosis and management SO VASA-EUROPEAN JOURNAL OF VASCULAR MEDICINE LA English DT Review DE May-Thurner syndrome; iliac vein compression ID COMMON ILIAC VEIN; DEEP VENOUS THROMBOSIS; INFERIOR VENA-CAVA; NONMALIGNANT OCCLUSIVE DISEASE; ILIOCAVAL COMPRESSION SYNDROME; PATENT FORAMEN OVALE; ENDOVASCULAR MANAGEMENT; INTRAVASCULAR ULTRASOUND; SURGICAL RECONSTRUCTION; ILIOFEMORAL VEINS AB For over fifty years, the pathogenesis of May-Thurner syndrome (MTS) has been associated with chronic left common iliac vein compression resulting in the formation of intraluminal, permanent obstructive lesions. However, despite this association, the mechanism by which compression produces these lesions is unknown. Diagnostic accuracy of MTS is critical since it often afflicts young patients requiring endovascular management. This review will focus on the historical, embryological and evolutionary description of MTS and examine its development, diagnosis, clinical management and potential diagnostic errors. C1 [Brazeau, Nicholas F.] Harvard Univ, Boston, MA 02114 USA. [Harvey, Harlan B.; Deipolyi, Amy; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Pinto, Erique G.] Hosp Prof Doutor Fernando Fonseca, Dept Imagiol, Amadora, Portugal. [Hesketh, Richard L.] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St GRB 290A, Boston, MA 02114 USA. OI Deipolyi, Amy/0000-0003-3144-386X NR 64 TC 10 Z9 14 U1 0 U2 11 PU VERLAG HANS HUBER HOGREFE AG PI BERN 9 PA LAENGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0301-1526 J9 VASA JI Vasa PD MAR PY 2013 VL 42 IS 2 BP 96 EP 105 DI 10.1024/0301-1526/a000252 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 109NC UT WOS:000316374300004 PM 23485836 ER PT J AU Ybarra, ML Korchmaros, J Kiwanuka, J Bangsberg, DR Bull, S AF Ybarra, Michele L. Korchmaros, Josephine Kiwanuka, Julius Bangsberg, David R. Bull, Sheana TI Examining the Applicability of the IMB Model in Predicting Condom Use Among Sexually Active Secondary School Students in Mbarara, Uganda SO AIDS AND BEHAVIOR LA English DT Article DE IMB model; Uganda; Adolescents; Condom use ID BEHAVIORAL SKILLS MODEL; SOUTH-AFRICAN ADOLESCENTS; INTIMATE PARTNER VIOLENCE; AIDS-RISK BEHAVIOR; HIV PREVENTION; REPRODUCTIVE HEALTH; INTERNET HARASSMENT; CAPE-TOWN; WOMEN; INFORMATION AB The applicability of the IMB model in predicting condom use was tested among 390 sexually active secondary school students in Mbarara, Uganda. Adolescents across five secondary schools completed a self-report survey about their health and sexual experiences. Based upon results from structural equation modeling, the IMB model partially predicts condom use. Condom use was directly predicted by HIV prevention information and behavioral skills regarding having and using condoms. It was indirectly predicted (through behavioral skills regarding having and using condoms) by behavioral intentions regarding using condoms and talking to one's partner about safer sex. Aspects of one's first sexual experience (i.e., age at first sex, having discussed using condoms with first sex partner, willingness at first sex) were strongly influential in predicting current condom use; this was especially true for discussing condoms with one's first sex partner. Findings highlight the importance of providing clear and comprehensive condom use training in HIV prevention programs aimed at Ugandan adolescents. They also underscore the importance of targeting abstinent youth before they become sexually active to positively affect their HIV preventive behavior at their first sexual experience. C1 [Ybarra, Michele L.; Korchmaros, Josephine] Ctr Innovat Publ Hlth Res Inc, San Clemente, CA USA. [Kiwanuka, Julius] Mbarara Univ Sci & Technol, Dept Pediat, Mbarara, Uganda. [Bangsberg, David R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Ragon Inst MGH MIT & Harva, Mbarara Univ Sci & Technol,Ctr Global Hlth, Cambridge, MA 02138 USA. [Bull, Sheana] Colorado Sch Publ Hlth, Denver, CO USA. RP Ybarra, ML (reprint author), Ctr Innovat Publ Hlth Res Inc, San Clemente, CA USA. EM Michele@InnovativePublicHealth.com FU NIMH NIH HHS [K24 MH087227, R01 MH054907, R01 MH080662, R01 MH080662-03, R01MH080662] NR 64 TC 5 Z9 5 U1 5 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD MAR PY 2013 VL 17 IS 3 BP 1116 EP 1128 DI 10.1007/s10461-012-0137-x PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 099VC UT WOS:000315649700027 PM 22350827 ER PT J AU Smith, SW Diercks, DB Nagurney, JT Hollander, JE Miller, CD Schrock, JW Singer, AJ Apple, FS McCullough, PA Ruff, CT Sesma, A Peacock, WF AF Smith, Stephen W. Diercks, Deborah B. Nagurney, John T. Hollander, Judd E. Miller, Chadwick D. Schrock, Jon W. Singer, Adam J. Apple, Fred S. McCullough, Peter A. Ruff, Christian T. Sesma, Arturo, Jr. Peacock, W. Frank CA MIDAS Investigators TI Central versus local adjudication of myocardial infarction in a cardiac biomarker trial SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Conference of the Society-for-Academic-Emergency-Medicine CY MAY, 2012 CL Chicago, IL SP Soc Acad Emergency Med, Alere, Biosite ID INTERNATIONAL CLINICAL-TRIAL; ACUTE CORONARY SYNDROMES; TROPONIN-I ASSAY; EARLY-DIAGNOSIS; END-POINTS; EVENTS; PREDICTION; COMMITTEE; RISK AB Objectives The impact of regulatory requirements, which require central adjudication for the diagnosis of acute myocardial infarction (AMI) in cardiac biomarker studies, is unclear. We determined the impact of local (at the site of subject enrollment) versus central adjudication of AMI on final diagnosis. Methods This is a retrospective analysis of data from the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study, an 18-center prospective study of patients with suspected acute coronary syndromes, with enrollment from December 19, 2006, to September 20, 2007. Local adjudication of AMI was performed by a single site investigator at each center following the protocol-specified definition and according to the year 2000 definition of AMI, which based cardiac troponin (cTn) elevation on local cut points for each of the 13 different assays. After completion of the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study primary analysis and to evaluate a new troponin assay, a Food and Drug Administration-mandated central adjudication was performed by 3 investigators at different institutions. This adjudication used the 2007 Universal Definition of AMI, which differs by use of the manufacturer's 99th percentile cTn cut point. We describe the outcome of this process and compare it with the local adjudication. Central adjudicators were not blinded to local adjudications. For central adjudication, discrepant diagnoses were resolved by consensus. Local versus central cTn cut points differed for 6 assays. Both definitions required a rise and/or fall of cTn. Discrepant cases were reviewed by the lead author. Difficult cases were defined as having a difference between local and central adjudication, an elevated cTn with a temporal rise and fall, and a negative or absent risk stratification test. Statistics were by chi(2), kappa, and logistic regression. Results Of 1,107 patients enrolled, 11 had indeterminate central adjudication, leaving 1,096 for analysis. In spite of high agreement across central versus local adjudicators, kappa = 0.79 (95% CI [0.73, 0.85]), AMI was diagnosed more often by central adjudication, 134 (12.2%) versus 104 (9.5%), with 44 local diagnoses (4%) changed from non-AMI to AMI (n = 37) or AMI to non-AMI (n = 7) (P < .001). These 44 represented 34% (95% CI 26%-42%) of 141 cases in which either central or local adjudication was AMI. Of diagnoses changed to AMI, 3 reasons contributed approximately one-third each: the local use of a non-99th percentile cTn cutoff (32%), the possibility of human error (34%), and difficult cases (34%). Conclusion Despite an acceptable., over a third of patients with a diagnosis of AMI were not assigned that diagnosis by both sets of adjudicators. This supports the importance of 1 standard method for diagnosis of AMI. (Am Heart J 2013;165:273-279.e1.) C1 [Smith, Stephen W.] Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA. [Smith, Stephen W.; Apple, Fred S.] Univ Minnesota, Minneapolis, MN USA. [Diercks, Deborah B.] Univ Calif Davis, Dept Emergency Med, Davis, CA 95616 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hollander, Judd E.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Miller, Chadwick D.] Wake Forest Sch Med, Dept Emergency Med, Winston Salem, NC USA. [Schrock, Jon W.] Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH USA. [Singer, Adam J.] SUNY Stony Brook, Dept Emergency Med, Stony Brook, NY 11794 USA. [Apple, Fred S.] Hennepin Cty Med Ctr, Dept Lab Med & Pathol, Minneapolis, MN 55415 USA. [McCullough, Peter A.] St John Providence Hlth Syst, Detroit, MI USA. [Ruff, Christian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Sesma, Arturo, Jr.] St Catherine Univ, Dept Psychol, St Paul, MN USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. RP Smith, SW (reprint author), Hennepin Emergency Dept, ER R-2,701 S Pk Ave, Minneapolis, MN 55415 USA. EM smith253@umn.edu OI Hollander, Judd/0000-0002-1318-2785 NR 17 TC 8 Z9 8 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2013 VL 165 IS 3 BP 273 EP + DI 10.1016/j.ahj.2012.12.012 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100OL UT WOS:000315710500007 PM 23453092 ER PT J AU Maynard, C Bradley, SM Bryson, CL AF Maynard, Charles Bradley, Steven M. Bryson, Chris L. TI The practice of transradial percutaneous coronary intervention in the Washington State Clinical Outcomes Assessment Program SO AMERICAN HEART JOURNAL LA English DT Article ID CARDIOVASCULAR DATA REGISTRY; TRANSFEMORAL APPROACH; FEMORAL ACCESS; ANGIOGRAPHY AB Background Transradial percutaneous coronary intervention (tPCI) as opposed to the femoral approach (fPCI) is associated with lower rates of bleeding. The purposes of this study were to describe the use of tPCI in the Washington State Clinical Outcomes Assessment Program, identify the predictors of bleeding, and determine whether tPCI was associated with less bleeding in women vs men, age <75 years vs >= 75 years, and baseline creatinine <2.0 mg/dL vs >= 2.0 mg/dL. Methods This study included 23,599 individuals who had a first tPCI or fPCI performed in 30 centers in Washington State in 2010 and 2011. Data were collected according to specifications from the American College of Cardiology National Cardiovascular Data Registry Cath-PCI version 4.3. The American College of Cardiology National Cardiovascular Data Registry bleeding model was used to calculate adjusted rates. Results Transradial percutaneous coronary intervention was used in only 5% of procedures, and in just 3 centers, tPCI was used in >10% of cases. Patient demographics and medical histories were similar in tPCI and fPCI, although the percent of acute cases was higher in fPCI (68% vs 45%, P < .0001). The overall bleeding rate was 2.2%, and the 3 most important predictors of bleeding were acute procedure, women, and age >= 75 years. For women, unadjusted rates of bleeding were 1.4% for tPCI and 4.0% for fPCI (P = .013). Among women, adjusted rates were almost 20% lower for tPCI (3.3% vs 4.1%). Conclusion In Washington State, tPCI was used infrequently, although it was associated with lower bleeding rates in high-risk groups including women. (Am Heart J 2013;165:332-7.) C1 [Maynard, Charles; Bryson, Chris L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Northwest Ctr Excellence, Seattle, WA USA. [Maynard, Charles; Bryson, Chris L.] Univ Washington, Seattle, WA 98195 USA. [Maynard, Charles; Bryson, Chris L.] Fdn Hlth Care Qual, Clin Outcomes Assessment Program, Seattle, WA USA. [Bradley, Steven M.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Bradley, Steven M.] Univ Colorado, Denver, CO 80202 USA. RP Maynard, C (reprint author), Hlth Serv Res & Dev, 1100 Olive Way 1400, Seattle, WA 98101 USA. EM cmaynard@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 12 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2013 VL 165 IS 3 BP 332 EP 337 DI 10.1016/j.ahj.2012.11.011 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100OL UT WOS:000315710500016 PM 23453101 ER PT J AU Hess, CN Rao, SV Kong, DF Miller, JM Anstrom, KJ Bertrand, OF Collet, JP Effron, MB Eloff, BC Fadiran, EO Farb, A Gilchrist, IC Holmes, DR Jacobs, AK Kaul, P Newby, LK Rutledge, DR Tavris, DR Tsai, TT White, RM Peterson, ED Krucoff, MW AF Hess, Connie N. Rao, Sunil V. Kong, David F. Miller, Julie M. Anstrom, Kevin J. Bertrand, Olivier F. Collet, Jean-Philippe Effron, Mark B. Eloff, Benjamin C. Fadiran, Emmanuel O. Farb, Andrew Gilchrist, Ian C. Holmes, David R. Jacobs, Alice K. Kaul, Prashant Newby, L. Kristin Rutledge, David R. Tavris, Dale R. Tsai, Thomas T. White, Roseann M. Peterson, Eric D. Krucoff, Mitchell W. TI TransRadial Education And Therapeutics (TREAT): Shifting the balance of safety and efficacy of antithrombotic agents in percutaneous coronary intervention. A report from the Cardiac Safety Research Consortium SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-OUTCOMES; FEMORAL APPROACH; VASCULAR COMPLICATIONS; ANTIPLATELET THERAPY; GENDER-DIFFERENCES; RANDOMIZED-TRIALS; HEART-ASSOCIATION; BLOOD-TRANSFUSION; ADVERSE OUTCOMES AB Percutaneous coronary intervention (PCI) is an integral part of the treatment of coronary artery disease. The most common complication of PCI, bleeding, typically occurs at the vascular access site and is associated with short-term and long-term morbidity and mortality. Periprocedural bleeding also represents the primary safety concern of concomitant antithrombotic therapies essential for PCI success. Use of radial access for PCI reduces procedural bleeding and hence may change the risk profile and net clinical benefit of these drugs. This new drug-device safety interaction creates opportunities to advance the safe and effective use of antithrombotic agents during PCI. In June 2010 and March 2011, leaders from government, academia, professional societies, device manufacturing, and pharmaceutical industries convened for 2 think tank meetings. Titled TREAT I and II, these forums examined approaches to improve the overall safety of PCI by optimizing strategies for antithrombotic drug use and radial artery access. This article summarizes the content and proceedings of these sessions. (Am Heart J 2013;165:344-353.e1.) C1 [Hess, Connie N.; Rao, Sunil V.; Kong, David F.; Anstrom, Kevin J.; Newby, L. Kristin; Peterson, Eric D.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Miller, Julie M.] Johns Hopkins Univ, Baltimore, MD USA. [Bertrand, Olivier F.] Quebec Heart Lung Inst, Quebec City, PQ, Canada. [Collet, Jean-Philippe] Inst Cardiol, Paris, France. [Effron, Mark B.] Lilly USA LLC, Indianapolis, IN USA. [Eloff, Benjamin C.; Fadiran, Emmanuel O.; Farb, Andrew; Tavris, Dale R.] US FDA, Silver Spring, MD USA. [Gilchrist, Ian C.] Penn State Heart & Vasc Inst, Hershey, PA USA. [Holmes, David R.] Mayo Clin, Rochester, MN USA. [Jacobs, Alice K.] Boston Med Ctr, Boston, MA USA. [Kaul, Prashant] Univ N Carolina, Chapel Hill, NC USA. [Rutledge, David R.; White, Roseann M.] Abbott Vasc, San Francisco, CA USA. [Tsai, Thomas T.] Denver VA Med Ctr, Denver, CO USA. RP Krucoff, MW (reprint author), Duke Clin Res Inst, 508 Fulton, Durham, NC 27705 USA. EM kruco001@mc.duke.edu RI Effron, Mark/P-9300-2015; OI Gilchrist, Ian/0000-0001-8525-8454 FU NIH [5T32HL069749-09] FX We thank Drs Morton J. Kern, Venugopal Menon, Tejas Patel, Jon R. Resar, Tara A. Ryan, Jeffrey E. Shuren, Norman Stockbridge, and Jean-Francois Tanguay for their reviews of this manuscript. C.N.H. was funded by NIH grant 5T32HL069749-09. NR 47 TC 3 Z9 3 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2013 VL 165 IS 3 BP 344 EP + DI 10.1016/j.ahj.2012.09.008 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100OL UT WOS:000315710500018 PM 23453103 ER PT J AU Neilan, TG Coelho, OR Shah, RV Feng, JZH Pena-Herrera, D Mandry, D Pierre-Mongeon, F Heydari, B Francis, SA Moslehi, J Kwong, RY Jerosch-Herold, M AF Neilan, Tomas G. Coelho-Filho, Otavio R. Shah, Ravi V. Feng, Jiazuo H. Pena-Herrera, Diego Mandry, Damien Pierre-Mongeon, Francois Heydari, Bobak Francis, Sanjeev A. Moslehi, Javid Kwong, Raymond Y. Jerosch-Herold, Michael TI Myocardial Extracellular Volume by Cardiac Magnetic Resonance Imaging in Patients Treated With Anthracycline-Based Chemotherapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; EJECTION FRACTION; MATRIX EXPANSION; HEART-FAILURE; FIBROSIS; QUANTIFICATION; ASSOCIATION; CARDIOMYOPATHY; MORTALITY; DISEASE AB We aimed to determine whether the myocardial extracellular volume (ECV), measured using T1 measurements obtained during cardiac magnetic resonance imaging were increased in patients treated with anthracyclines. We performed cardiac magnetic resonance imaging and echocardiography and measured the ECV in 42 patients treated with anthracyclines. The data from the cardiac magnetic resonance study were compared to those from healthy volunteers. The anthracycline-treated cohort consisted of 21 men and 21 women with a mean age of 55 +/- 17 years, who presented a median of 84 months after chemotherapy with a cumulative anthracycline exposure of 282 +/- 65 mg/m(2) and a mean left ventricular ejection fraction of 52 +/- 12%. The ECV was elevated in the anthracycline-treated patients compared to the age- and gender-matched controls (0.36 +/- 0.03 vs 0.28 +/- 0.02, p <0.001). A positive association was found between the ECV and left atrial volume (ECV vs indexed left atrial volume, r = 0.65, p <0.001), and negative association was found between the ECV and diastolic function (E' lateral, r = -0.64, p <0.001). In conclusion, the myocardial ECV is elevated in patients with previous anthracycline treatment and is associated with the diastolic function and increased atrial volumes. (c) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:717-722) C1 [Neilan, Tomas G.; Coelho-Filho, Otavio R.; Shah, Ravi V.; Feng, Jiazuo H.; Pena-Herrera, Diego; Mandry, Damien; Pierre-Mongeon, Francois; Heydari, Bobak; Moslehi, Javid; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Neilan, Tomas G.; Shah, Ravi V.; Francis, Sanjeev A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Moslehi, Javid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Neilan, TG (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. EM tneilan@partners.org OI Feng, Jiazuo/0000-0002-6974-2956 FU American Heart Association (Dallas, Texas) [12FTF12060588]; National Institutes of Health (Bethesda, Maryland) [T32 HL094301-02]; Health Career Development grant from the National Institutes of Health [K08HL097031-02]; [R01HL090634-01A1]; [R01HL091157] FX This work was supported in part by Fellow to Faculty grant 12FTF12060588 from the American Heart Association (Dallas, Texas), T32 Training grant T32 HL094301-02 (to T. G. Neilan) from the National Institutes of Health (Bethesda, Maryland), Health Career Development grant K08HL097031-02) (to J. Moslehi) from the National Institutes of Health, and project grants R01HL090634-01A1 (to M. Jerosch-Herold) and R01HL091157 (to R. Y. Kwong). NR 25 TC 34 Z9 34 U1 1 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 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2013 VL 111 IS 5 BP 717 EP 722 DI 10.1016/j.amjcard.2012.11.022 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100AH UT WOS:000315666600016 PM 23228924 ER PT J AU Goldsmith, EC Bradshaw, AD Spinale, FG AF Goldsmith, Edie C. Bradshaw, Amy D. Spinale, Francis G. TI Cellular Mechanisms of Tissue Fibrosis. 2. Contributory pathways leading to myocardial fibrosis: moving beyond collagen expression SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE fibrosis; collagen; myocardium; extracellular matrix ID PROCOLLAGEN C-PROTEINASE; VENTRICULAR PRESSURE-OVERLOAD; BONE MORPHOGENETIC PROTEIN-1; MARROW-DERIVED CELLS; FRIZZLED-RELATED PROTEIN-2; NEWLY SYNTHESIZED COLLAGEN; EHLERS-DANLOS-SYNDROME; CARDIAC FIBROBLASTS; MYOFIBROBLAST DIFFERENTIATION; MATRIX METALLOPROTEINASES AB Goldsmith EC, Bradshaw AD, Spinale FG. Cellular Mechanisms of Tissue Fibrosis. 2. Contributory pathways leading to myocardial fibrosis: moving beyond collagen expression. Am J Physiol Cell Physiol 304: C393-C402, 2013. First published November 21, 2012; doi: 10.1152/ajpcell.00347.2012.-While the term "fibrosis" can be misleading in terms of the complex patterns and processes of myocardial extracellular matrix (ECM) remodeling, fibrillar collagen accumulation is a common consequence of relevant pathophysiological stimuli, such as pressure overload (PO) and myocardial infarction (MI). Fibrillar collagen accumulation in both PO and MI is predicated on a number of diverse cellular and extracellular events, which include changes in fibroblast phenotype (transdifferentiation), post-translational processing and assembly, and finally, degradation. The expansion of a population of transformed fibroblasts/myofibroblasts is a significant cellular event with respect to ECM remodeling in both PO and MI. The concept that this cellular expansion within the myocardial ECM may be due, at least in part, to endothelial-mesenchymal transformation and thereby not dissimilar to events observed in cancer progression holds intriguing future possibilities. Studies regarding determinants of procollagen processing, such as procollagen C-endopeptidase enhancer (PCOLCE), and collagen assembly, such as the secreted protein acidic and rich in cysteine (SPARC), have identified potential new targets for modifying the fibrotic response in both PO and MI. Finally, the transmembrane matrix metalloproteinases, such as MMP-14, underscore the diversity and complexity of this ECM proteolytic family as this protease can degrade the ECM as well as induce a profibrotic response. The growing recognition that the myocardial ECM is a dynamic entity containing a diversity of matri-cellular and nonstructural proteins as well as proteases and that the fibrillar collagens can change in structure and content in a rapid temporal fashion has opened up new avenues for modulating what was once considered an irreversible event - myocardial fibrosis. C1 [Goldsmith, Edie C.; Spinale, Francis G.] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29208 USA. [Spinale, Francis G.] Univ S Carolina, Sch Med, Cardiovasc Translat Res Ctr, Columbia, SC 29208 USA. [Spinale, Francis G.] WJB Dorn Vet Affairs Med Ctr, Columbia, SC USA. [Bradshaw, Amy D.] Med Univ S Carolina, Div Cardiol, Columbia, SC USA. [Bradshaw, Amy D.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Spinale, FG (reprint author), Univ S Carolina, Sch Med, CBA, Cardiovasc Translat Res Ctr, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM cvctrc@uscmed.sc.edu FU National Institutes of Health [HL-057952, HL-089944, HL-095608, HL-111090, HL-097214, HL-094517]; Veterans' Affairs Health Administration [5I01BX000168, 1I01BX001385] FX This work was supported by National Institutes of Health Grants HL-057952, HL-089944, HL-095608, HL-111090, HL-097214, and HL-094517 and by Merit Awards (5I01BX000168 and 1I01BX001385) from the Veterans' Affairs Health Administration. NR 98 TC 45 Z9 47 U1 0 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAR PY 2013 VL 304 IS 5 BP C393 EP C402 DI 10.1152/ajpcell.00347.2012 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 100EX UT WOS:000315680300001 PM 23174564 ER PT J AU Dowdy, DW Basu, S Andrews, JR AF Dowdy, David W. Basu, Sanjay Andrews, Jason R. TI Is Passive Diagnosis Enough? The Impact of Subclinical Disease on Diagnostic Strategies for Tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE tuberculosis; diagnostic techniques and procedures; models; theoretical; epidemiology ID SMEAR-POSITIVE TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; UNDIAGNOSED TUBERCULOSIS; RANDOMIZED-TRIAL; HIV; PREVALENCE; REINFECTION; COMMUNITY; TRANSMISSION; PROGRESSION AB Rationale: Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited. Objectives: To estimate the population-level impact of TB case-finding strategies in the presence of subclinical and prediagnostic disease. Methods: We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active"). Measurements and Main Results: If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase. Conclusions: Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection. C1 [Dowdy, David W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Dowdy, David W.] Johns Hopkins Univ, Ctr TB Res, Baltimore, MD USA. [Basu, Sanjay] Stanford Univ, Prevent Res Ctr, Dept Med, Palo Alto, CA 94304 USA. [Basu, Sanjay] London Sch Hyg & Trop Med, Dept Publ Hlth & Policy, London WC1, England. [Andrews, Jason R.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Dowdy, DW (reprint author), 615 North Wolfe St,E6531, Baltimore, MD 21205 USA. EM ddowdy@jhsph.edu OI Andrews, Jason/0000-0002-5967-251X FU National Institutes of Health [T32 AI007433, 1R21AI101152] FX Supported in part by grants T32 AI007433 (J.R.A.) and 1R21AI101152 (D.W.D.) from the National Institutes of Health. NR 42 TC 27 Z9 27 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2013 VL 187 IS 5 BP 543 EP 551 DI 10.1164/rccm.201207-1217OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 104FL UT WOS:000315977200014 PM 23262515 ER PT J AU Kim, KW Krajewski, KM Jagannathan, JP Nishino, M Shinagare, AB Hornick, JL Ramaiya, NH AF Kim, Kyung Won Krajewski, Katherine M. Jagannathan, Jyothi P. Nishino, Mizuki Shinagare, Atul B. Hornick, Jason L. Ramaiya, Nikhil H. TI Cancer of Unknown Primary Sites: What Radiologists Need to Know and What Oncologists Want to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE carcinoma of unknown primary sites; diagnosis; imaging; immunohistochemistry; occult primary ID POSITRON-EMISSION-TOMOGRAPHY; SERUM TUMOR-MARKERS; CARCINOMA; MANAGEMENT; METASTASES; STATISTICS; GUIDELINES; DIAGNOSIS; SEARCH; PET/CT AB OBJECTIVE. In this article, we review the role of imaging in cancer of unknown primary site (CUP) diagnosis and management and the utility of immunohistochemistry, serum tumor markers, and molecular profiling in the optimized care of CUP patients. CONCLUSION. With advances in imaging, pathology, and molecular medicine, the diagnosis and management of CUP have evolved into more personalized and site-specific therapies. A multidisciplinary integrated approach among oncologists, pathologists, and radiologists is extremely important. C1 [Kim, Kyung Won; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Nishino, Mizuki; Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Kim, Kyung Won] Seoul Asan Med Ctr, Dept Radiol, Seoul, South Korea. [Hornick, Jason L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. RP Kim, KW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM medimash@gmail.com FU (NCI) from the National Institutes of Health [1K23CA157631] FX M. Nishino was supported by grant 1K23CA157631 (NCI) from the National Institutes of Health. NR 38 TC 11 Z9 11 U1 0 U2 7 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2013 VL 200 IS 3 BP 484 EP 492 DI 10.2214/AJR.12.9363 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 105GM UT WOS:000316054500018 PM 23436835 ER PT J AU Lim, R Khawaja, RDA Nimkin, K Sagar, P Shailam, R Gee, MS Westra, SJ AF Lim, Ruth Khawaja, Ranish Deedar Ali Nimkin, Katherine Sagar, Pallavi Shailam, Randheer Gee, Michael S. Westra, Sjirk J. TI Relationship Between Radiologist Training Level and Fluoroscopy Time for Voiding Cystourethrography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE fluoroscopy; radiation exposure; radiologist education; voiding cystourethrography ID RADIATION-DOSE REDUCTION; URINARY-TRACT-INFECTION; PEDIATRIC FLUOROSCOPY; VESICOURETERAL REFLUX; CANCER RISK; EXPOSURE; CHILDREN; FILTRATION; INFANTS; PAUSE AB OBJECTIVE. The objective of our study was to determine whether voiding cystourethrography (VCUG) fluoroscopy time is related to the training level of the performing radiologist. MATERIALS AND METHODS. VCUG reports with normal findings from 2008 to 2011 at one institution were retrospectively reviewed. The average fluoroscopy time was calculated for first-year radiology residents, senior radiology residents, pediatric radiology fellows, and attending pediatric radiologists. The average fluoroscopy time was also calculated for radiologist sex, patient sex, and patient age group. The analysis of variance was used to evaluate differences in average fluoroscopy times between training levels of radiologists, patient age groups, and patient sexes. RESULTS. We reviewed 784 VCUG reports with normal findings: 340 (43.4%) were performed by first-year residents; 181 (23%), by senior residents; 161 (20.5%), by fellows; and 102 (13%), by attending pediatric radiologists. The overall average fluoroscopy time was 1.86 minutes (SD +/- 0.98). The attending pediatric radiologists had the shortest average fluoroscopy time (1.63 +/- 0.92 minutes), significantly shorter than senior residents (1.96 +/- 1.09 minutes; p = 0.0070) and fellows (1.91 +/- 0.85 minutes; p = 0.0255). There was no significant difference between attending radiologists and first-year residents (1.85 +/- 1.00 minutes; p = 0.0550). The male-to-female ratio of radiologists was 54% versus 46%, with identical average fluoroscopy times: male radiologists, 1.86 +/- 1.05 minutes; female radiologists, 1.86 +/- 0.90 minutes. There was no significant difference in average fluoroscopy times among patient age groups: 1.93, 1.76, and 1.78 minutes, respectively, for groups A (0-1 years), B (> 1 to <= 5 years), and C (> 5 years) (p = 0.1750, 0.4605, 0.6303). The average fluoroscopy time for male patients (2.02 +/- 1.00 minutes) was significantly longer than that for female patients (1.71 +/- 0.95 minutes; p < 0.0001). CONCLUSION. Attending pediatric radiologists have the shortest fluoroscopy time; the differences between their average time compared with the average times of pediatric radiology fellows and of senior radiology residents were statistically significant. The average fluoroscopy time is longer for male patients than for female patients. C1 [Lim, Ruth; Nimkin, Katherine; Sagar, Pallavi; Shailam, Randheer; Gee, Michael S.; Westra, Sjirk J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Pediat Imaging, Boston, MA 02114 USA. [Khawaja, Ranish Deedar Ali] Aga Khan Univ, Sch Med, Karachi, Pakistan. RP Lim, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Pediat Imaging, 34 Fruit St,Ellison 237, Boston, MA 02114 USA. EM rlim@partners.org NR 19 TC 9 Z9 9 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2013 VL 200 IS 3 BP 645 EP 651 DI 10.2214/AJR.12.8902 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 105GM UT WOS:000316054500040 PM 23436857 ER PT J AU Verma, S Harisinghani, M AF Verma, Sadhna Harisinghani, Mukesh TI Limitations, Disabilities, and Pitfalls of Dynamic Contrast-Enhanced MRI as a Diagnostic Modality in Prostate Cancer Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 [Verma, Sadhna] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Verma, S (reprint author), Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. NR 2 TC 0 Z9 0 U1 1 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2013 VL 200 IS 3 BP W327 EP W327 DI 10.2214/AJR.12.9873 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 105GM UT WOS:000316054500015 PM 23547334 ER PT J AU Desai, R Miller, KW Raines, DE AF Desai, Rooma Miller, Keith W. Raines, Douglas E. TI The Pyrrole Etomidate Analog Carboetomidate Potently Inhibits Human 5-HT3A Receptor Function: Comparisons with Etomidate and Potential Implications for Emetogenesis SO ANESTHESIA AND ANALGESIA LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; SEROTONIN; ANTAGONISTS; PREVENTION; CHANNELS AB BACKGROUND: 5-Hydroxytryptamine type 3 (5-HT3) receptors are excitatory ion channels belonging to the cys-loop family of ligand-gated ion channels. They are involved in nausea and vomiting and their antagonists are used clinically as antiemetic drugs. We previously reported the development of a novel pyrrole analog of etomidate, (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), which retains etomidate's desirable anesthetic and hemodynamic properties, but lacks its potent inhibitory effect on adrenocorticotropic hormone stimulated steroid synthesis. Also in contrast to etomidate, carboetomidate potently inhibits nicotinic acetylcholine receptors. Because nicotinic acetylcholine and 5-HT3 receptors are highly homologous, we hypothesized that carboetomidate might also potently inhibit 5-HT3 receptors with potentially important implications for the drug's emetogenic activity. In the current studies, we investigated and compared modulation of 5-HT3A receptors by carboetomidate and etomidate. METHODS: 5-HT3 receptors were heterologously expressed in human embryonic kidney cells. Drugs were applied with a multichannel superfusion pipette coupled to piezoelectric elements, and currents were recorded from cells in either the whole-cell or excised outside-out patch configuration of patch-clamp recordings. RESULTS: Carboetomidate and etomidate inhibited integrated 5-HT3A receptor mediated currents with respective half-inhibitory concentrations of 1.9 mu M (95% confidence interval [CI] = 1.4-2.7 mu M) and 251 mu M (95% CI = 17-37 mu M). These values may be compared with respective hypnotic concentrations of 5.4 and 2.3 mu M. This inhibition reflected hypnotic effects on peak current amplitudes and desensitization rates. Half-inhibitory concentrations for reducing peak current amplitudes were 34 mu M (95% CI = 24-48 mu M) for carboetomidate and 171 mu M (95% CI = 128-228 mu M) for etomidate. Half-inhibitory concentrations for reducing the desensitization time constant were 3.5 mu M (95% CI = 2.4-5.1 mu M) for carboetomidate and 36 mu M (95% CI = 21-59 mu M) for etomidate. CONCLUSIONS: In contrast to etomidate, carboetomidate inhibits 5-HT3A receptor mediated currents at hypnotic concentrations. This inhibition is primarily the result of enhancing the rate of desensitization. Because carboetomidate potently inhibits 5-HT3A receptors, it may be less emetogenic than etomidate. (Anesth Analg 2013;116:573-9) C1 [Desai, Rooma; Miller, Keith W.; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM draines@partners.org FU National Institutes of Health [2P01-GM058448-11, R01-GM087316, R21-DA029253] FX Supported by National Institutes of Health grants 2P01-GM058448-11, R01-GM087316, and R21-DA029253. NR 22 TC 3 Z9 4 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2013 VL 116 IS 3 BP 573 EP 579 DI 10.1213/ANE.0b013e31827d204d PG 7 WC Anesthesiology SC Anesthesiology GA 098HQ UT WOS:000315540400013 PM 23400978 ER PT J AU Pierce, ET Kumar, V Zheng, H Peterfreund, RA AF Pierce, Eric T. Kumar, Vikram Zheng, Hui Peterfreund, Robert A. TI Medication and Volume Delivery by Gravity-Driven Micro-Drip Intravenous Infusion: Potential Variations During "Wide-Open" Flow SO ANESTHESIA AND ANALGESIA LA English DT Article AB BACKGROUND: Gravity-driven micro-drip infusion sets allow control of medication dose delivery by adjusting drops per minute. When the roller clamp is fully open, flow in the drip chamber can be a continuous fluid column rather than discrete, countable, drops. We hypothesized that during this "wide-open" state, drug delivery becomes dependent on factors extrinsic to the micro-drip set and is therefore difficult to predict. We conducted laboratory experiments to characterize volume delivery under various clinically relevant conditions of wide-open flow in an in vitro laboratory model. METHODS: A micro-drip infusion set, plugged into a bag of normal saline, was connected to a high-flow stopcock at the distal end. Vertically oriented IV catheters (gauges 14-22) were connected to the stopcock. The fluid meniscus height in the bag was fixed (60-120 cm) above the outflow point. The roller clamp on the infusion set was in fully open position for all experiments resulting in a continuous column of fluid in the drip chamber. Fluid volume delivered in 1 minute was measured 4 times with each condition. To model resistive effects of carrier flow, volumetric infusion pumps were used to deliver various flow rates of normal saline through a carrier IV set into which a micro-drip infusion was "piggybacked." We also compared delivery by micro-drip infusion sets from 3 manufacturers. RESULTS: The volume of fluid delivered by gravity-driven infusion under wide-open conditions (continuous fluid column in drip chamber) varied 2.9-fold (95% confidence interval, 2.84-2.96) depending on catheter size and fluid column height. Total model resistance of the micro-drip with stopcock and catheter varied with flow rate. Volume delivered by the piggybacked micro-drip decreased up to 29.7% +/- 0.8% (mean +/- SE) as the carrier flow increased from 0 to 1998 mL/min. Delivery characteristics of the micro-drip infusion sets from 3 different manufacturers were similar. CONCLUSIONS: Laboratory simulation of clinical situations with gravity-driven micro-drip infusion sets under wide-open flow conditions revealed that infusion rate (drug and/or volume delivery) can vary widely depending on extrinsic factors including catheter size, fluid column height, and carrier flow. The variable resistance implies nonlaminar flow in the micro-drip model that cannot be easily predicted mathematically. These findings support the use of mechanical pumps instead of gravity-driven micro-drips to enhance the precision and safety of IV infusions, especially for vasoactive drugs. (Anesth Analg 2013;116:614-18) C1 [Pierce, Eric T.; Kumar, Vikram; Peterfreund, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Sch Med, Boston, MA 02114 USA. [Zheng, Hui] Harvard Univ, Massachusetts Gen Hosp, Ctr Biostat, Sch Med, Boston, MA 02114 USA. RP Pierce, ET (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM etpierce@partners.org NR 7 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2013 VL 116 IS 3 BP 614 EP 618 DI 10.1213/ANE.0b013e31827bc235 PG 5 WC Anesthesiology SC Anesthesiology GA 098HQ UT WOS:000315540400019 PM 23400996 ER PT J AU Yoon, J Park, J Choi, M Choi, WJ Choi, C AF Yoon, Jonghee Park, Junseong Choi, Myunghwan Choi, Won Jong Choi, Chulhee TI Application of femtosecond-pulsed lasers for direct optical manipulation of biological functions SO ANNALEN DER PHYSIK LA English DT Article DE Biophotonics; calcium; cell signaling; lighttissue interaction; low-density plasma; optical modulation; photontissue interaction; reactive oxygen species; ultrashort-pulsed lasers; femtosecond-pulsed laser ID (ROS)-INDUCED ROS RELEASE; IN-VIVO; PHOTODYNAMIC THERAPY; CARDIAC MYOCYTES; CALCIUM; OXYGEN; CELLS; MUSCLE; ABLATION; MITOCHONDRIA AB Absorption of photon energy by cells or tissue can evoke photothermal, photomechanical, and photochemical effects, depending on the density of the deposited energy. Photochemical effects require a low energy density and can be used for reversible modulation of biological functions. Ultrashort-pulsed lasers have a high intensity due to the short pulse duration, despite its low average energy. Through nonlinear absorption, these lasers can deliver very high peak energy into the submicrometer focus area without causing collateral damage. Absorbed energy delivered by ultrashort-pulsed laser irradiation induces free electrons, which can be readily converted to reactive oxygen species (ROS) and related free radicals in the localized region. Free radicals are best known to induce irreversible biological effects via oxidative modification; however, they have also been proposed to modulate biological functions by releasing calcium ions from intracellular organelles. Calcium can evoke variable biological effects in both excitable and nonexcitable cell types. Controlled stimulation by ultrashort laser pulses generate intracellular calcium waves that can modulate many biological functions, such as cardiomyocyte beat rate, muscle contractility, and bloodbrain barrier (BBB) permeability. This article presents optical methods that are useful therapeutic and research tools in the biomedical field and discuss the possible mechanisms responsible for biological modulation by ultrashort-pulsed lasers, especially femtosecond-pulsed lasers. C1 [Yoon, Jonghee; Park, Junseong; Choi, Won Jong; Choi, Chulhee] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. [Choi, Myunghwan] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305701, South Korea. [Choi, Myunghwan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Choi, Myunghwan] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Choi, Chulhee] Korea Adv Inst Sci & Technol, Inst BioCentury, Taejon 305701, South Korea. RP Choi, C (reprint author), Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. EM cchoi@kaist.ac.kr RI Choi, Chulhee/C-1642-2011; Park, Junseong/C-1973-2012; OI Choi, Chulhee/0000-0001-5542-9136; Park, Junseong/0000-0003-0436-8614; Choi, Myunghwan/0000-0002-4235-7003 FU Brain Research Center of the 21st Century Frontier Research Program [2011K000286]; Ministry of Education, Science and Technology, the Republic of Korea FX This research was supported by a grant (2011K000286) from the Brain Research Center of the 21st Century Frontier Research Program, funded by the Ministry of Education, Science and Technology, the Republic of Korea (to C.C.). NR 76 TC 4 Z9 4 U1 0 U2 27 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0003-3804 J9 ANN PHYS-BERLIN JI Ann. Phys.-Berlin PD MAR PY 2013 VL 525 IS 3 BP 205 EP + DI 10.1002/andp.201200099 PG 10 WC Physics, Multidisciplinary SC Physics GA 100PT UT WOS:000315713900001 ER PT J AU Huffman, DM Augenlicht, LH Zhang, XY Lofrese, JJ Atzmon, G Chamberland, JP Mantzoros, CS AF Huffman, Derek M. Augenlicht, Leonard H. Zhang, Xueying Lofrese, John J. Atzmon, Gil Chamberland, John P. Mantzoros, Christos S. TI Abdominal Obesity, Independent from Caloric Intake, Accounts for the Development of Intestinal Tumors in Apc1638N/+ Female Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID BODY-MASS INDEX; HIGH-FAT DIET; COLON-CANCER; INSULIN-RESISTANCE; OVARIAN HORMONES; SURGICAL REMOVAL; RECTAL-CANCER; US ADULTS; RISK; GROWTH AB To determine whether visceral fat (VF), independent of other confounders, is causally linked to intestinal tumorigenesis, we surgically removed visceral fat in Apc(1638/N+) mice. At 15 weeks of age, male and female Apc(1638/N+) mice were randomized to one of three groups: ad libitum, visceral fat removal (VF-) and ad libitum fed, or caloric restriction, and were studied for effects on tumorigenesis and survival. As compared with ad libitum, VF- and caloric restriction reduced macroadenomas to a similar extent (P < 0.05), but only caloric restriction significantly improved survival (P < 0.05). Given that a significant group x gender interaction was observed, we next examined males and females separately. In females, macroadenomas were markedly attenuated by VF- (1.33 +/- 0.23 mean +/- SE; P < 0.05), but not by caloric restriction (2.35 +/- 0.25; P = 0.71), as compared with ad libitum(2.50 +/- 0.34). In males, however, caloric restriction (1.71 +/- 0.26; P < 0.01), but not VF- (2.94 +/- 0.42; P = 0.29), reduced macroadenomas, as compared with ad libitum males (3.47 +/- 0.30). In females, both VF- (P = 0.05) and caloric restriction (P < 0.01) improved survival, but not in male mice (P = 0.15). The benefits observed with caloric restriction were consistent with favorable metabolic adaptations, but protection conferred in VF- females was despite lower adiponectin levels (P < 0.05), and failure to reduce body mass, total adiposity, glucose, insulin, leptin, and chemokine (C-X-C motif) ligand 1 (CXCL-1) levels. In conclusion, these data provide the first causal evidence linking visceral fat to intestinal cancer risk, and suggest that factors, other than known metabolic mediators, may impact tumor development. Furthermore, these data emphasize that strategies designed to deplete visceral fat stores in humans should be considered in the prevention of intestinal cancer. Cancer Prev Res; 6(3); 177-87. (C) 2012 AACR. C1 [Huffman, Derek M.; Augenlicht, Leonard H.; Zhang, Xueying; Lofrese, John J.; Atzmon, Gil] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Atzmon, Gil] Yeshiva Univ Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Augenlicht, Leonard H.] Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. [Huffman, Derek M.; Lofrese, John J.; Atzmon, Gil] Yeshiva Univ Albert Einstein Coll Med, Inst Aging Res, Bronx, NY 10461 USA. [Zhang, Xueying] Chinese Acad Sci, Inst Zool, Beijing, Peoples R China. [Chamberland, John P.; Mantzoros, Christos S.] VA Boston Healthcare Syst, Dept Internal Med, Sect Endocrinol, Boston, MA USA. [Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Internal Med,Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Huffman, DM (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Med, Inst Aging Res, Div Endocrinol, 1300 Morris Pk Ave,Golding Bldg Room 502, Bronx, NY 10461 USA. EM derek.huffman@einstein.yu.edu OI Chamberland, John/0000-0002-7862-1371 FU Prevent Cancer Foundation; National Institute on Aging [AG037574]; Einstein Nathan Shock Center Healthy Aging Physiology Core [P30AG038072]; Diabetes Research and Training Center at the Albert Einstein College of Medicine [DK20541]; National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX This work has been supported by grants from the Prevent Cancer Foundation and National Institute on Aging (AG037574) to D. M. Huffman, and the Einstein Nathan Shock Center Healthy Aging Physiology Core (P30AG038072) and the Diabetes Research and Training Center (DK20541) at the Albert Einstein College of Medicine. C.S. Mantzoros is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929, and 81913 as well as Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 42 TC 11 Z9 11 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAR PY 2013 VL 6 IS 3 BP 177 EP 187 DI 10.1158/1940-6207.CAPR-12-0414 PG 11 WC Oncology SC Oncology GA 102UI UT WOS:000315869300004 PM 23466815 ER PT J AU Morikawa, T Kuchiba, A Lochhead, P Nishihara, R Yamauchi, M Imamura, Y Liao, XY Qian, ZR Ng, K Chan, AT Meyerhardt, JA Giovannucci, E Fuchs, CS Ogino, S AF Morikawa, Teppei Kuchiba, Aya Lochhead, Paul Nishihara, Reiko Yamauchi, Mai Imamura, Yu Liao, Xiaoyun Qian, Zhi Rong Ng, Kimmie Chan, Andrew T. Meyerhardt, Jeffrey A. Giovannucci, Edward Fuchs, Charles S. Ogino, Shuji TI Prospective Analysis of Body Mass Index, Physical Activity, and Colorectal Cancer Risk Associated with beta-Catenin (CTNNB1) Status SO CANCER RESEARCH LA English DT Article ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; POSTMENOPAUSAL HORMONE-THERAPY; LIFE-STYLE FACTORS; ISLAND METHYLATOR PHENOTYPE; UNIQUE TUMOR PRINCIPLE; MICROSATELLITE INSTABILITY; PERSONALIZED MEDICINE; OLDER WOMEN; METAANALYSIS; EXPRESSION AB Dysregulation of the WNT/beta-catenin (CTNNB1) signaling pathway is implicated in colorectal carcinoma and metabolic diseases. Considering these roles and cancer prevention, we hypothesized that tumor CTNNB1 status might influence cellular sensitivity to obesity and physical activity. In clinical follow-up of 109,046 women in the Nurses' Health Study and 47,684 men in the Health Professionals Follow-up Study, there were 861 incident rectal and colon cancers with tissue immunohistochemistry data on nuclear CTNNB1 expression. Using this molecular pathological epidemiology database, we conducted Cox proportional hazards regression analysis using data duplication method to assess differential associations of body mass index (BMI) or exercise activity with colorectal cancer risk according to tumor CTNNB1 status. Greater BMI was associated with a significantly higher risk of CTNNB1-negative cancer [multivariate HR = 1.34; 95% confidence interval (CI), 1.18-1.53 for 5.0 kg/m(2) increment; P-trend = 0.0001] but not with CTNNB1-positive cancer risk (multivariate HR = 1.07; 95% CI, 0.92-1.25 for 5.0 kg/m(2) increment; P-trend = 0.36; P-heterogeneity = 0.027, between CTNNB1-negative and CTNNB1-positive cancer risks). Physical activity level was associated with a lower risk of CTNNB1-negative cancer (multivariate HR = 0.93; 95% CI, 0.87-1.00 for 10 MET-h/wk increment; P-trend = 0.044) but not with CTNNB1-positive cancer risk (multivariate HR = 0.98; 95% CI, 0.91-1.05 for 10 MET-h/wk increment; Ptrend 0.60). Our findings argue that obesity and physical inactivity are associated with a higher risk of CTNNB1-negative colorectal cancer but not with CTNNB1-positive cancer risk. Furthermore, they suggest that energy balance and metabolism status exerts its effect in a specific carcinogenesis pathway that is less likely dependent on WNT/CTNNB1 activation. Cancer Res; 73(5); 1600-10. (C) 2012 AACR. C1 [Morikawa, Teppei; Kuchiba, Aya; Lochhead, Paul; Nishihara, Reiko; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Qian, Zhi Rong; Ng, Kimmie; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles S.] Harvard Univ, Sch Med, Dept Med, Channing Div Network Med, Boston, MA 02215 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU U.S. NIH [P01CA87969, P01CA55075, P50CA127003, R01CA151993, K07 CA148894, R01CA137178]; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science; Harvard University Frank Knox Memorial Fellowship FX This work was supported by U.S. NIH grants P01CA87969 (S.E. Hankinson), P01CA55075 (W.C. Willett), P50CA127003 (C.S. Fuchs), R01CA151993 (S. Ogino), K07 CA148894 (K. Ng), and R01CA137178 (A.T. Chan) and by grants from the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. A.T. Chan is a Damon Runyon Clinical Investigator. T. Morikawa was supported by a fellowship grant from the Japan Society for Promotion of Science. P. Lochhead was a Scottish Government Clinical Academic Fellow and was supported by a Harvard University Frank Knox Memorial Fellowship. NR 50 TC 37 Z9 37 U1 1 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2013 VL 73 IS 5 BP 1600 EP 1610 DI 10.1158/0008-5472.CAN-12-2276 PG 11 WC Oncology SC Oncology GA 100YM UT WOS:000315741500016 PM 23442321 ER PT J AU Marshall, AL Christiani, DC AF Marshall, Ariela L. Christiani, David C. TI Genetic susceptibility to lung cancerulight at the end of the tunnel? SO CARCINOGENESIS LA English DT Review ID GLUTATHIONE-S-TRANSFERASE; DNA-REPAIR GENES; NUCLEOTIDE-EXCISION-REPAIR; MICROSOMAL EPOXIDE HYDROLASE; GENOME-WIDE ASSOCIATION; NICOTINIC ACETYLCHOLINE-RECEPTOR; TP53 ARG72PRO POLYMORPHISM; CODON 72 POLYMORPHISM; MYELOPEROXIDASE G-463A POLYMORPHISM; QUINONE OXIDOREDUCTASE POLYMORPHISM AB Lung cancer is one of the most common and deadliest cancers in the world. The major socio-environmental risk factor involved in the development of lung cancer is cigarette smoking. Additionally, there are multiple genetic factors, which may also play a role in lung cancer risk. Early work focused on the presence of relatively prevalent but low-penetrance alterations in candidate genes leading to increased risk of lung cancer. Development of new technologies such as genomic profiling and genome-wide association studies has been helpful in the detection of new genetic variants likely involved in lung cancer risk. In this review, we discuss the role of multiple genetic variants and review their putative role in the risk of lung cancer. Identifying genetic biomarkers and patterns of genetic risk may be useful in the earlier detection and treatment of lung cancer patients. C1 [Marshall, Ariela L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institutes of Health [CA074386, CA092824, CA090578] FX National Institutes of Health grants (CA074386, CA092824 and CA090578). NR 299 TC 29 Z9 31 U1 0 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2013 VL 34 IS 3 BP 487 EP 502 DI 10.1093/carcin/bgt016 PG 16 WC Oncology SC Oncology GA 099NR UT WOS:000315629000001 PM 23349013 ER PT J AU Sabbatino, F Ferrone, S AF Sabbatino, Francesco Ferrone, Soldano TI Can the "Right" EGFR-Specific mAb Dramatically Improve EGFR-Targeted Therapy? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID C-RECEPTOR POLYMORPHISMS; CANCER-THERAPY; ANTIBODY; CETUXIMAB; EFFICACY AB EGF receptor (EGFR)-specific monoclonal antibodies (mAb) display limited therapeutic efficacy in EGFR-positive solid tumors. To overcome this limitation, the significant improvement of the antibody-dependent cell-mediated cytotoxicity-mediated antitumor activity of a novel EGFR-specific mAb is described. Its potential impact on the efficacy of immunotherapy for EGFR-positive solid tumors is discussed. Clin Cancer Res; 19(5); 958-60. (C) 2013 AACR. C1 [Sabbatino, Francesco; Ferrone, Soldano] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Ferrone, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM sferrone@partners.org OI Sabbatino, Francesco/0000-0001-6431-8278 FU PHS grants [RO1 CA110249, RO1 CA138188]; National Cancer Institute FX This work was supported by PHS grants RO1 CA110249 and RO1 CA138188 awarded by the National Cancer Institute (to S. Ferrone). NR 12 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2013 VL 19 IS 5 BP 958 EP 960 DI 10.1158/1078-0432.CCR-12-3586 PG 3 WC Oncology SC Oncology GA 100YB UT WOS:000315740200002 PM 23340298 ER PT J AU Agarwal, A Ghobrial, IM AF Agarwal, Amit Ghobrial, Irene M. TI Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma: A Review of the Current Understanding of Epidemiology, Biology, Risk Stratification, and Management of Myeloma Precursor Disease SO CLINICAL CANCER RESEARCH LA English DT Review ID BONE-MARROW ENVIRONMENT; LIGHT-CHAIN RATIO; SIGNIFICANCE MGUS; PLASMA-CELLS; MALIGNANT-TRANSFORMATION; ADULT-POPULATION; NATURAL-HISTORY; PROGRESSION; PREVALENCE; PATHOGENESIS AB The term monoclonal gammopathy of undetermined significance (MGUS) was coined in 1978. The recent advances in our knowledge about MGUS and smoldering multiple myeloma (SMM) have helped us better understand the pathogenesis of myeloma. It seems that myeloma evolves from a precursor state in almost all cases. We do not completely understand the multistep process from the precursor state to myeloma, but studies like whole genome sequencing continue to improve our understanding of this process. The process of transformation may not be linear acquisition of changes, but rather a branched heterogeneous process. Clinical features that are prognostic of rapid transformation have been identified, but no specific molecular markers have been identified. Even with recent advances, multiple myeloma remains an incurable disease in the vast majority, and intervening at the precursor state provides a unique opportunity to alter the natural history of the disease. A limitation is that a vast majority of patients with precursor disease, especially low-risk MGUS, will never progress to myeloma in their lifetime, and treating these patients is not only unnecessary but may be potentially harmful. The challenge is to identify a subset of patients with the precursor state that would definitely progress to myeloma and in whom interventions will have a meaningful impact. As our understanding of the molecular and genetic processes improves, these studies will guide the selection of high-risk patients more appropriately and ultimately direct a tailored management strategy to either delay progression to symptomatic myeloma or even "cure" a person at this premalignant stage. Clin Cancer Res; 19(5); 985-94. (C) 2012 AACR. C1 [Agarwal, Amit] Univ Arizona, Div Hematol Oncol, Tucson, AZ USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu FU [R01CA125690]; [R01CA133799]; [R01CA154648] FX I.M. Ghobrial is supported in part by grants R01CA125690, R01CA133799, and R01CA154648. NR 72 TC 23 Z9 24 U1 2 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2013 VL 19 IS 5 BP 985 EP 994 DI 10.1158/1078-0432.CCR-12-2922 PG 10 WC Oncology SC Oncology GA 100YB UT WOS:000315740200006 PM 23224402 ER PT J AU Lohavanichbutr, P Mendez, E Holsinger, FC Rue, TC Zhang, YZ Houck, J Upton, MP Futran, N Schwartz, SM Wang, P Chen, C AF Lohavanichbutr, Pawadee Mendez, Eduardo Holsinger, F. Christopher Rue, Tessa C. Zhang, Yuzheng Houck, John Upton, Melissa P. Futran, Neal Schwartz, Stephen M. Wang, Pei Chen, Chu TI A 13-Gene Signature Prognostic of HPV-Negative OSCC: Discovery and External Validation SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PLASMINOGEN-ACTIVATOR INHIBITOR; HUMAN-PAPILLOMAVIRUS; GENE-EXPRESSION; OROPHARYNGEAL CANCER; LUNG-CANCER; ORAL-CANCER; HIGH-RISK; RECEPTOR; SURVIVAL AB Purpose: To identify a prognostic gene signature for patients with human papilloma virus (HPV)negative oral squamous cell carcinomas (OSCC). Experimental Design: Two gene expression datasets were used: a training dataset from the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA; n = 97) and a validation dataset from the MD Anderson Cancer Center (MDACC, Houston, TX; n = 71). We applied L1/L2-penalized Cox regression models to the FHCRC data on the 131-gene signature previously identified to be prognostic in patients with OSCCs to identify a prognostic model specific for patients with high-risk HPV-negative OSCCs. The models were tested with the MDACC dataset using a receiver operating characteristic (ROC) analysis. Results: A 13-gene model was identified as the best predictor of HPV-negative OSCC-specific survival in the training dataset. The risk score for each patient in the validation dataset was calculated from this model and dichotomized at the median. The estimated 2-year mortality (+/- SE) of patients with high-risk scores was 47.1% (+/- 9.24%) compared with 6.35% (+/- 4.42) for patients with low-risk scores. ROC analyses showed that the areas under the curve for the age, gender, and treatment modality-adjusted models with risk score [0.78; 95% confidence interval (CI), 0.74-0.86] and risk score plus tumor stage (0.79; 95% CI, 0.75-0.87) were substantially higher than for the model with tumor stage (0.54; 95% CI, 0.48-0.62). Conclusions: We identified and validated a 13-gene signature that is considerably better than tumor stage in predicting survival of patients with HPV-negative OSCCs. Further evaluation of this gene signature as a prognostic marker in other populations of patients with HPV-negative OSCC is warranted. Clin Cancer Res; 19(5); 1197-203. (C) 2012 AACR. C1 [Lohavanichbutr, Pawadee; Houck, John; Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. [Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Zhang, Yuzheng; Wang, Pei] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98109 USA. [Mendez, Eduardo; Futran, Neal; Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Rue, Tessa C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. [Holsinger, F. Christopher] Univ Texas Houston, MD Anderson Canc Ctr, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. RP Chen, C (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Avenue North,M5-C800,POB 19024, Seattle, WA 98109 USA. EM cchen@fhcrc.org OI Schwartz, Stephen/0000-0001-7499-8502 FU NIH, National Cancer Institute [NIH NCI R01CA095419]; National Center for Research Resources grant [1KL2RR025015-01]; Amos Medical Faculty Development Program Award from the Robert Wood Johnson Foundation; Fred Hutchinson Cancer Research Center; Specialized Program of Research Excellence in Head and Neck Cancer Grant from the National Cancer Institute [P50CA97007]; Clinician Investigator Program in Translational Research [K12CA088084]; Clinical Research Program [2 L30CA117652-02A1]; THANC Foundation Young Investigator Award FX The study at FHCRC was supported by grants from the NIH, National Cancer Institute (NIH NCI R01CA095419), National Center for Research Resources grant 1KL2RR025015-01, Amos Medical Faculty Development Program Award from the Robert Wood Johnson Foundation, and by institutional funds from the Fred Hutchinson Cancer Research Center. The study at the MD Anderson Cancer Center was supported by Specialized Program of Research Excellence in Head and Neck Cancer Grant P50CA97007 from the National Cancer Institute, "Clinician Investigator Program in Translational Research" K12CA088084, Clinical Research Program 2 L30CA117652-02A1, and THANC Foundation Young Investigator Award in Head and Neck Cancer. NR 37 TC 18 Z9 18 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2013 VL 19 IS 5 BP 1197 EP 1203 DI 10.1158/1078-0432.CCR-12-2647 PG 7 WC Oncology SC Oncology GA 100YB UT WOS:000315740200027 PM 23319825 ER PT J AU Frederick, DT Piris, A Cogdill, AP Cooper, ZA Lezcano, C Ferrone, CR Mitra, D Boni, A Newton, LP Liu, CW Peng, WY Sullivan, RJ Lawrence, DP Hodi, FS Overwijk, WW Lizee, G Murphy, GF Hwu, P Flaherty, KT Fisher, DE Wargo, JA AF Frederick, Dennie T. Piris, Adriano Cogdill, Alexandria P. Cooper, Zachary A. Lezcano, Cecilia Ferrone, Cristina R. Mitra, Devarati Boni, Andrea Newton, Lindsay P. Liu, Chengwen Peng, Weiyi Sullivan, Ryan J. Lawrence, Donald P. Hodi, F. Stephen Overwijk, Willem W. Lizee, Gregory Murphy, George F. Hwu, Patrick Flaherty, Keith T. Fisher, David E. Wargo, Jennifer A. TI BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RAF INHIBITION; RESISTANCE; MEK; IMMUNOTHERAPY; VEMURAFENIB; MUTATIONS; THERAPY AB Purpose: To evaluate the effects of BRAF inhibition on the tumor microenvironment in patients with metastatic melanoma. Experimental Design: Thirty-five biopsies were collected from 16 patients with metastatic melanoma pretreatment (day 0) and at 10 to 14 days after initiation of treatment with either BRAF inhibitor alone (vemurafenib) or BRAF + MEK inhibition (dabrafenib + trametinib) and were also taken at time of progression. Biopsies were analyzed for melanoma antigens, T-cell markers, and immunomodulatory cytokines. Results: Treatment with either BRAF inhibitor alone or BRAF + MEK inhibitor was associated with an increased expression of melanoma antigens and an increase in CD8+ T-cell infiltrate. This was also associated with a decrease in immunosuppressive cytokines [interleukin (IL)-6 and IL-8] and an increase in markers of T-cell cytotoxicity. Interestingly, expression of exhaustion markers TIM-3 and PD1 and the immunosuppressive ligand PDL1 was increased on treatment. A decrease in melanoma antigen expression and CD8 T-cell infiltrate was noted at time of progression on BRAF inhibitor alone and was reversed with combined BRAF and MEK inhibition. Conclusions: Together, these data suggest that treatment with BRAF inhibition enhances melanoma antigen expression and facilitates T-cell cytotoxicity and a more favorable tumor microenvironment, providing support for potential synergy of BRAF-targeted therapy and immunotherapy. Interestingly, markers of T-cell exhaustion and the immunosuppressive ligand PDL1 are also increased with BRAF inhibition, further implying that immune checkpoint blockade may be critical in augmenting responses to BRAF-targeted therapy in patients with melanoma. Clin Cancer Res; 19(5); 1225-31. (C) 2013 AACR. C1 [Frederick, Dennie T.; Cogdill, Alexandria P.; Cooper, Zachary A.; Ferrone, Cristina R.; Boni, Andrea; Newton, Lindsay P.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Sullivan, Ryan J.; Lawrence, Donald P.; Flaherty, Keith T.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Piris, Adriano] Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. [Mitra, Devarati; Fisher, David E.] Massachusetts Gen Hosp, Div Dermatol, Boston, MA 02114 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lezcano, Cecilia; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02115 USA. [Liu, Chengwen; Peng, Weiyi; Overwijk, Willem W.; Lizee, Gregory; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Ctr Canc Immunol Res, Houston, TX 77030 USA. RP Wargo, JA (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM jwargo@partners.org OI Murphy, George/0000-0003-3464-793X; Cogdill, Alexandria/0000-0001-8917-9462; Cooper, Zachary/0000-0003-1059-0940 FU NIH [1K08CA160692-01A1, 1U54CA163125-01]; MGH Vaccine and Immunotherapy Center; Claflin Distinguished Scholar Award FX This work is supported by NIH grants 1K08CA160692-01A1 (J.A. Wargo) and 1U54CA163125-01 (J.A. Wargo, K.T. Flaherty, and F.S. Hodi), the MGH Vaccine and Immunotherapy Center (J.A. Wargo), and the Claflin Distinguished Scholar Award (J.A. Wargo), and through the generous philanthropic support of several families whose lives have been affected by melanoma. NR 23 TC 258 Z9 265 U1 7 U2 51 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2013 VL 19 IS 5 BP 1225 EP 1231 DI 10.1158/1078-0432.CCR-12-1630 PG 7 WC Oncology SC Oncology GA 100YB UT WOS:000315740200030 PM 23307859 ER PT J AU Schneider, BP Gray, RJ Radovich, M Shen, F Vance, G Li, L Jiang, GL Miller, KD Gralow, JR Dickler, MN Cobleigh, MA Perez, EA Shenkier, TN Nielsen, KV Muller, S Thor, A Sledge, GW Sparano, JA Davidson, NE Badve, SS AF Schneider, Bryan P. Gray, Robert J. Radovich, Milan Shen, Fei Vance, Gail Li, Lang Jiang, Guanglong Miller, Kathy D. Gralow, Julie R. Dickler, Maura N. Cobleigh, Melody A. Perez, Edith A. Shenkier, Tamara N. Nielsen, Kirsten Vang Muller, Sven Thor, Ann Sledge, George W., Jr. Sparano, Joseph A. Davidson, Nancy E. Badve, Sunil S. TI Prognostic and Predictive Value of Tumor Vascular Endothelial Growth Factor Gene Amplification in Metastatic Breast Cancer Treated with Paclitaxel with and without Bevacizumab; Results from ECOG 2100 Trial SO CLINICAL CANCER RESEARCH LA English DT Article ID PLUS ADJUVANT CHEMOTHERAPY; PHASE-III; TRASTUZUMAB; BIOMARKERS; THERAPY; ASSOCIATION; EXPRESSION; DOCETAXEL; CARCINOMA; HYPOXIA AB Purpose: Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here. Experimental Design: E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted. Results: Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR- tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2-. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P = 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant. Conclusion: VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab. Clin Cancer Res; 19(5); 1281-9. (C) 2012 AACR. C1 [Schneider, Bryan P.; Radovich, Milan; Shen, Fei; Vance, Gail; Li, Lang; Jiang, Guanglong; Miller, Kathy D.; Sledge, George W., Jr.; Badve, Sunil S.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Gray, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gralow, Julie R.] Puget Sound Oncol Consortium, Seattle, WA USA. [Dickler, Maura N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cobleigh, Melody A.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Perez, Edith A.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Shenkier, Tamara N.] BCCA Vancouver Canc Ctr, Vancouver, BC, Canada. [Nielsen, Kirsten Vang; Muller, Sven] Dako Denmark, Glostrup, Denmark. [Thor, Ann] Univ Colorado, Denver, CO 80202 USA. [Sparano, Joseph A.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Schneider, BP (reprint author), Indiana Univ Sch Med, Dept Med, Div Hematol Oncol, Indianapolis, IN 46202 USA. EM bpschnei@iupui.edu OI Nielsen, Kirsten Vang/0000-0001-7956-1748 FU Public Health Service [CA23318, CA66636, CA21115, CA49883, CA16116, CA32102, CA20319, CA14958, CA77651, CA12027, CA25224]; National Cancer Institute; NIH; Department of Health and Human Services; Breast Cancer Research Foundation; [R-01 CA155311-01A1] FX This study was coordinated by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA49883, CA16116, CA32102, CA20319, CA14958, CA77651, CA12027, CA25224 and from the National Cancer Institute, NIH, and the Department of Health and Human Services. The science was also supported by an R-01 CA155311-01A1 (B.P. Schneider; principal investigator). The procurement and preparation of samples was supported by the Breast Cancer Research Foundation. NR 44 TC 22 Z9 23 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2013 VL 19 IS 5 BP 1281 EP 1289 DI 10.1158/1078-0432.CCR-12-3029 PG 9 WC Oncology SC Oncology GA 100YB UT WOS:000315740200035 PM 23340303 ER PT J AU McCleary, NJ Odejide, O Szymonifka, J Ryan, D Hezel, A Meyerhardt, JA AF McCleary, Nadine Jackson Odejide, Oreofe Szymonifka, Jackie Ryan, David Hezel, Aram Meyerhardt, Jeffrey A. TI Safety and Effectiveness of Oxaliplatin-Based Chemotherapy Regimens in Adults 75 Years and Older With Colorectal Cancer SO CLINICAL COLORECTAL CANCER LA English DT Article DE Chemotherapy toxicity; Colorectal cancer; Comparative effectiveness; Comorbid medical conditions; Elderly; Oxaliplatin ID COMPREHENSIVE GERIATRIC ASSESSMENT; III COLON-CANCER; CLINICAL-TRIALS; ADJUVANT CHEMOTHERAPY; AGE; DISPARITIES; SURVIVAL; BARRIERS; THERAPY AB Although the safety and efficacy of oxaliplatin-based chemotherapy regimens for colorectal cancer (CRC) have been demonstrated in adults >= 75 years of age enrolled in clinical trials, safety and effectiveness outside the trial setting are less established. In this comparative effectiveness study, we note that older adults with stage III and metastatic CRC treated outside of a clinical trial experienced safety and effectiveness of oxaliplatin-based chemotherapy regimens comparable to that of younger adults. Background: Although the safety and efficacy of oxaliplatin-based chemotherapy regimens for colorectal cancer (CRC) have been demonstrated in adults >= 75 years of age who are enrolled in clinical trials, safety and effectiveness outside the trial setting are less established. Methods: We retrospectively collected cases of patients >= 75 years of age who were diagnosed with stage III and metastatic CRC and initiated treatment between January 2000 and January 2007 at 2 academic hospitals in Boston, MA. Cases were matched in a 1:2 ratio to controls who were < 75 years of age by hospital site, stage of disease (stage III vs. metastatic) and line of therapy (first- or second-line or beyond). The primary study endpoints were grade 3 treatment-associated toxicities and intolerance (number of dose delays/reductions and hospital/facility admissions during treatment). The secondary endpoint was overall survival. Results: We identified 84 patients 75 years of age (25% >= 80 years) and 168 controls. In the cohort, 77% had colon cancer, 75% had metastatic disease, and 60% were receiving oxaliplatin as first-line therapy. There was no significant difference in grade >= 3 treatment-associated toxicities between the patients and the controls (71.4% vs. 68.5%, respectively; P = .63). Further there was no statistically significant difference between patients and controls for combined endpoints of any grade >= 3 toxicity or hospital/facility admission (P = .92). With a median follow-up of 52 months, 2-year overall survival was similar between patients and controls (43% vs. 52%, respectively; P = .87). Conclusion: Older adults with stage III and metastatic CRC treated outside of a clinical trial experienced safety and effectiveness of oxaliplatin-based chemotherapy regimens that was comparable to that of younger adults. Clinical Colorectal Cancer, Vol. 12, No. 1, 62-9 (C) 2013 Elsevier Inc. All rights reserved. C1 [McCleary, Nadine Jackson; Odejide, Oreofe; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Szymonifka, Jackie] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Ryan, David] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Hezel, Aram] Univ Rochester, Med Ctr, Wilmot Canc Ctr, Rochester, NY 14642 USA. RP McCleary, NJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM nj_mccleary@dfci.harvard.edu FU American Society of Clinical Oncologists Young Investigator Award; Program in Cancer Outcomes Research Training NIH [R25CA092203]; Dana-Farber Cancer Institute gastrointestinal SPORE Career Development Award [NIH 5P50CA127003-05] FX This work was supported by the American Society of Clinical Oncologists Young Investigator Award, Program in Cancer Outcomes Research Training NIH R25CA092203, Dana-Farber Cancer Institute gastrointestinal SPORE Career Development Award NIH 5P50CA127003-05. NR 22 TC 12 Z9 12 U1 0 U2 7 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD MAR PY 2013 VL 12 IS 1 BP 62 EP 69 DI 10.1016/j.clcc.2012.09.001 PG 8 WC Oncology SC Oncology GA 102GS UT WOS:000315833500009 PM 23102897 ER PT J AU Goldstein, SL Jaber, BL Faubel, S Chawla, LS AF Goldstein, Stuart L. Jaber, Bertrand L. Faubel, Sarah Chawla, Lakhmir S. CA Amer Soc Nephrology TI AKI Transition of Care: A Potential Opportunity to Detect and Prevent CKD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; STEM-CELL TRANSPLANTATION; CRITICALLY-ILL CHILDREN; LONG-TERM RISK; CARDIAC-SURGERY; CARDIOVASCULAR-DISEASE; HOSPITALIZED-PATIENTS; PROSPECTIVE COHORT AB The incidence rate of AKI is increasing across the spectrum of hospitalized children and adults. Given the increased morbidity and mortality associated with AKI, significant research effort has been appropriately focused on standardizing AKI definitions, identifying risk factors, and discovering and validating novel, earlier structural biomarkers of kidney injury. In addition, a growing body of evidence demonstrates that AKI is a risk factor for the future development or accelerated progression of CKD. Unfortunately, prospective observational studies have not consistently followed survivors of episodes of AKI for longitudinal outcomes after hospital discharge, which could lead to ascertainment bias in terms of over- or underestimation of CKD development. Furthermore, data show that clinical follow-up of AKI survivors is low. This lack of systematic study and clinical follow-up represents a potential missed opportunity to prevent chronic disease after an acute illness and improve outcomes. Therefore, prospective study of transitions of care after episodes of AKI is needed to identify which patients are at risk for CKD development and to optimally target therapeutic interventions. Clin J Am Soc Nephrol 8: 476-483, 2013. doi: 10.2215/CJN.12101112 C1 [Goldstein, Stuart L.] Cincinnati Childrens Hosp Med Ctr, Ctr Acute Care Nephrol, Cincinnati, OH 45229 USA. [Jaber, Bertrand L.] Tufts Univ, Sch Med, Dept Med, St Elizabeths Med Ctr,Div Nephrol, Boston, MA 02111 USA. [Faubel, Sarah] Univ Colorado, Div Nephrol, Denver, CO 80202 USA. [Faubel, Sarah] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chawla, Lakhmir S.] George Washington Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Washington, DC 20037 USA. RP Goldstein, SL (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 7022,RILF 2, Cincinnati, OH 45229 USA. EM stuart.goldstein@cchmc.org FU NIDDK NIH HHS [R01 DK075976, R01 DK088923] NR 75 TC 54 Z9 55 U1 0 U2 7 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 MAR PY 2013 VL 8 IS 3 BP 476 EP 483 DI 10.2215/CJN.12101112 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 102GP UT WOS:000315833200020 PM 23471414 ER PT J AU Munshi, MN Segal, AR Suhl, E Ryan, C Sternthal, A Giusti, J Lee, Y Fitzgerald, S Staum, E Bonsignor, P DesRochers, L McCartney, R Weinger, K AF Munshi, Medha N. Segal, Alissa R. Suhl, Emmy Ryan, Courtney Sternthal, Adrianne Giusti, Judy Lee, Yishan Fitzgerald, Shane Staum, Elizabeth Bonsignor, Patricia DesRochers, Laura McCartney, Richard Weinger, Katie TI Assessment of Barriers to Improve Diabetes Management in Older Adults A randomized controlled study SO DIABETES CARE LA English DT Article ID DYSFUNCTION; MELLITUS; VALIDITY AB OBJECTIVE-To evaluate whether assessment of barriers to self-care and strategies to cope with these barriers in older adults with diabetes is superior to usual care with attention control. The American Diabetes Association guidelines recommend the assessment of age-specific barriers. However, the effect of such strategy on outcomes is unknown. RESEARCH DESIGN AND METHODS-We randomized 100 subjects aged >= 69 years with poorly controlled diabetes (A1C >8%) in two groups. A geriatric diabetes team assessed barriers and developed strategies to help patients cope with barriers for an intervention group. The control group received equal amounts of attention time. The active intervention was performed for the first 6 months, followed by a "no-contact" period. Outcome measures included A1C, Tinetti test, 6-min walk test (6MWT), self-care frequency, and diabetes-related distress. RESULTS-We assessed 100 patients (age 75 +/- 5 years, duration 21 +/- 13 years, 68% type 2 diabetes, 89% on insulin) over 12 months. After the active period, A1C decreased by -0.45% in the intervention group vs. -0.31% in the control group. At 12 months, A1C decreased further in the intervention group by -0.21% vs. 0% in control group (linear mixed-model, P < 0.03). The intervention group showed additional benefits in scores on measures of self-care (Self-Care Inventory-R), gait and balance (Tinetti), and endurance (6MWT) compared with the control group. Diabetes-related distress improved in both groups. CONCLUSIONS-Only attention between clinic visits lowers diabetes-related distress in older adults. However, communication with an educator cognizant of patients' barriers improves glycemic control and self-care frequency, maintains functionality, and lowers distress in this population. Diabetes Care 36:543-549, 2013 C1 [Munshi, Medha N.; Segal, Alissa R.; Suhl, Emmy; Ryan, Courtney; Sternthal, Adrianne; Giusti, Judy; Lee, Yishan; Fitzgerald, Shane; Staum, Elizabeth; Bonsignor, Patricia; DesRochers, Laura; McCartney, Richard; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Munshi, Medha N.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Munshi, Medha N.; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Segal, Alissa R.] Massachusetts Coll Pharm Hlth Sci, Boston, MA USA. RP Munshi, MN (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM mmunshi@bidmc.harvard.edu FU American Diabetes Association [1-07-CR-40]; U.S. Department of Defense Peer Reviewed Medical Research Program of the Office of the Congressionally Directed Medical Research Programs [W81XWH-07-1-0282]; sanofi-aventis FX The study was partly supported by a grant from a clinical research award from the American Diabetes Association, 1-07-CR-40 (M.N.M.), and partly from the U.S. Department of Defense Peer Reviewed Medical Research Program of the Office of the Congressionally Directed Medical Research Programs, W81XWH-07-1-0282 (M.N.M.).; M.N.M. received research funding from sanofi-aventis. No other potential conflicts of interest relevant to this article were reported. NR 23 TC 11 Z9 11 U1 4 U2 19 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2013 VL 36 IS 3 BP 543 EP 549 DI 10.2337/dc12-1303 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 103OU UT WOS:000315928700018 PM 23193208 ER PT J AU Falvey, CM Rosano, C Simonsick, EM Harris, T Strotmeyer, ES Satterfield, S Yaffe, K AF Falvey, Cherie M. Rosano, Caterina Simonsick, Eleanor M. Harris, Tamara Strotmeyer, Elsa S. Satterfield, Suzanne Yaffe, Kristine CA Hlth ABC Study TI Macro- and Microstructural Magnetic Resonance Imaging Indices Associated With Diabetes Among Community-Dwelling Older Adults SO DIABETES CARE LA English DT Article ID DIFFUSION TENSOR MRI; WHITE-MATTER; COGNITIVE DECLINE; SPATIAL STATISTICS; ALZHEIMERS-DISEASE; HUMAN BRAIN; TYPE-2; MELLITUS; ATROPHY; ABNORMALITIES AB OBJECTIVE-To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (RO1s) in a group of community-dwelling elders with and without diabetes. RESEARCH DESIGN AND METHODS-MRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized beta values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROIs. Models were adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total brain volume (TBV). RESULTS-In multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMHs. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results. CONCLUSIONS-In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline. Diabetes Care 36:677-682,2013 C1 [Falvey, Cherie M.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Falvey, Cherie M.; Yaffe, Kristine] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Rosano, Caterina; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Falvey, CM (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM cherie.falvey@ucsf.edu RI Strotmeyer, Elsa/F-3015-2014; OI Rosano, Caterina/0000-0002-0909-1506; Strotmeyer, Elsa/0000-0002-4093-6036; Rosano, Caterina/0000-0002-4271-6010 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research [R01-NR012459]; National Institutes of Health (NIH), NIA; American Health Assistance Foundation [A201-0029]; NIA [K24AG031155]; NIH (NIA, National Institute of Diabetes and Digestive and Kidney Diseases, and NIMH); Department of Defense; American Health Assistance Foundation; Anonymous Foundation; Alzheimer's Association; NIH/NIA; NIH FX This work was supported by National Institute on Aging (NIA) grants N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, and R01-AG028050 and National Institute of Nursing Research Grant R01-NR012459. This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), NIA, and American Health Assistance Foundation Grant A201-0029. K.Y. is supported in part by NIA Grant K24AG031155. K.Y. has served on data safety-monitoring boards for the NIH (National Institute of Mental Health [NIMH] and NIA trials) and has received research support from the NIH (NIA, National Institute of Diabetes and Digestive and Kidney Diseases, and NIMH), Department of Defense, American Health Assistance Foundation, Anonymous Foundation, and Alzheimer's Association. S.S. receives research support from the NIH/NIA. T.H. receives research support from the NIH. NR 40 TC 33 Z9 38 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2013 VL 36 IS 3 BP 677 EP 682 DI 10.2337/dc12-0814 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 103OU UT WOS:000315928700040 PM 23160721 ER PT J AU Qi, QB Meigs, JB Rexrode, KM Hu, FB Qi, L AF Qi, Qibin Meigs, James B. Rexrode, Kathryn M. Hu, Frank B. Qi, Lu TI Diabetes Genetic Predisposition Score and Cardiovascular Complications Among Patients With Type 2 Diabetes SO DIABETES CARE LA English DT Article ID RISK; DISEASE; VARIANTS; ATHEROSCLEROSIS; POPULATION; MORTALITY; OBESITY; WOMEN AB OBJECTIVE-To examine the association between genetic predisposition to type 2 diabetes (T2D) and risk of cardiovascular disease (CVD) among patients with T2D. RESEARCH DESIGN AND METHODS-The current study included 1,012 men and 1,310 women with T2D from the Health Professionals Follow-up Study and Nurses' Health Study, including 677 patients with CVD and 1,645 non-CVD control subjects. A genetic predisposition score (GPS) was calculated on the basis of 36 established independent diabetes-predisposing variants. RESULTS-Each additional diabetes-risk allele in the GPS was associated with a 3% increased risk of CVD (odds ratio [OR] 1.03 [95% CI 1.00-1.06]). The OR was 1.47 (1.11-1.95) for CVD risk by comparing extreme quartiles of the GPS (P for trend = 0.01). We also found that the GPS was positively associated with hemoglobin A(1c) levels (P = 0.009). CONCLUSIONS-Genetic predisposition to T2D is associated with an increased risk of cardiovascular complications in patients with T2D. Diabetes Care 36:737-739,2013 C1 [Qi, Qibin; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Gen Med Div, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Rexrode, Kathryn M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Rexrode, Kathryn M.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu OI Rexrode, Kathryn/0000-0003-3387-8429 FU National Institutes of Health [DK-091718, HL-071981, HL-073168, CA-87969, CA-49449, HL-34594, HL-088521, U01-HG-004399, DK-080140, DK-58845, DK-46200]; American Heart Association [0730094N] FX This study was supported by grants DK-091718, HL-071981, HL-073168, CA-87969, CA-49449, HL-34594, HL-088521, U01-HG-004399, DK-080140, DK-58845, and DK-46200 from the National Institutes of Health. L.Q. is a recipient of the American Heart Association Scientist Development Award (0730094N). NR 15 TC 7 Z9 7 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2013 VL 36 IS 3 BP 737 EP 739 DI 10.2337/dc12-0852 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 103OU UT WOS:000315928700050 PM 23069839 ER PT J AU Simic, P Zainabadi, K Bell, E Sykes, DB Saez, B Lotinun, S Baron, R Scadden, D Schipani, E Guarente, L AF Simic, Petra Zainabadi, Kayvan Bell, Eric Sykes, David B. Saez, Borja Lotinun, Sutada Baron, Roland Scadden, David Schipani, Ernestina Guarente, Leonard TI SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating beta-catenin SO EMBO MOLECULAR MEDICINE LA English DT Article DE bone; cartilage; fat; mesenchymal stem cells; sirtuin ID SUPPRESSES OSTEOGENIC DIFFERENTIATION; RUNX2 GENE-EXPRESSION; BONE-MARROW; OSTEOBLAST DIFFERENTIATION; CAENORHABDITIS-ELEGANS; PROMOTES PROLIFERATION; CALORIE RESTRICTION; OXIDATIVE STRESS; STROMAL CELLS; LIFE-SPAN AB Mesenchymal stem cells (MSCs) are multi-potent cells that can differentiate into osteoblasts, adipocytes, chondrocytes and myocytes. This potential declines with aging. We investigated whether the sirtuin SIRT1 had a function in MSCs by creating MSC specific SIRT1 knock-out (MSCKO) mice. Aged MSCKO mice (2.2 years old) showed defects in tissues derived from MSCs; i.e. a reduction in subcutaneous fat, cortical bone thickness and trabecular volume. Young mice showed related but less pronounced effects. MSCs isolated from MSCKO mice showed reduced differentiation towards osteoblasts and chondrocytes in vitro, but no difference in proliferation or apoptosis. Expression of -catenin targets important for differentiation was reduced in MSCKO cells. Moreover, while -catenin itself (T41A mutant resistant to cytosolic turnover) accumulated in the nuclei of wild-type MSCs, it was unable to do so in MSCKO cells. However, mutating K49R or K345R in -catenin to mimic deacetylation restored nuclear localization and differentiation potential in MSCKO cells. We conclude that SIRT1 deacetylates -catenin to promote its accumulation in the nucleus leading to transcription of genes for MSC differentiation. C1 [Simic, Petra; Zainabadi, Kayvan; Bell, Eric; Guarente, Leonard] MIT, Dept Biol, Glenn Lab Sci Aging, Cambridge, MA 02139 USA. [Sykes, David B.; Saez, Borja; Scadden, David] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Dept Oral Med, Sch Dent Med Infect & Immun, Boston, MA 02115 USA. [Schipani, Ernestina] MGH Harvard Med Sch, Endocrinol Unit, Boston, MA USA. RP Guarente, L (reprint author), MIT, Dept Biol, Glenn Lab Sci Aging, Cambridge, MA 02139 USA. EM leng@mit.edu OI Lotinun, Sutada/0000-0002-5127-3039 FU Fulbright Association; NIH; [F32 CA 132358] FX We wish to thank Eric O. Williams for help during the preparation of the manuscript. This work is supported by Fulbright Association post-doctoral fellowship to P. S., F32 CA 132358 to E. L. B. and grants from the NIH and a gift from the Glenn Medical Foundation to L.G. NR 64 TC 69 Z9 76 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD MAR PY 2013 VL 5 IS 3 BP 430 EP 440 DI 10.1002/emmm.201201606 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 102RH UT WOS:000315861200010 PM 23364955 ER PT J AU Lubitz, SA Rienstra, M AF Lubitz, Steven A. Rienstra, Michiel TI Genetic susceptibility to atrial fibrillation: does heart failure change our perspective? SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Editorial Material ID CHROMOSOME 4Q25; LIFETIME RISK; VARIANTS; ASSOCIATION; STROKE; ZFHX3 AB This editorial refers to 'Genetic polymorphisms confer risk of atrial fibrillation in patients with heart failure: a population-based study', by J.G. Smith et al., published in this issue on pages 250-257. C1 [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.] Cardiovasc Res Inst, Boston, MA USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. RP Rienstra, M (reprint author), Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Hanzepl 1, NL-9700 RB Groningen, Netherlands. EM m.rienstra@umcg.nl RI sebastianovitsch, stepan/G-8507-2013; OI Rienstra, Michiel/0000-0002-2581-070X NR 22 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAR PY 2013 VL 15 IS 3 BP 244 EP 246 DI 10.1093/eurjhf/hft005 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 106RD UT WOS:000316161500002 PM 23315103 ER PT J AU Smith, JG Melander, O Sjogren, M Hedblad, B Engstrom, G Newton-Cheh, C Platonov, PG AF Smith, J. Gustav Melander, Olle Sjogren, Marketa Hedblad, Bo Engstrom, Gunnar Newton-Cheh, Christopher Platonov, Pyotr G. TI Genetic polymorphisms confer risk of atrial fibrillation in patients with heart failure: a population-based study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Atrial fibrillation; Heart failure; Genetic association; Risk factors; Genetic predisposition ID CHROMOSOME 4Q25; VARIANTS; SUSCEPTIBILITY; MORTALITY; DIAGNOSIS; REGISTER; THERAPY; COHORT; STAT3; ZFHX3 AB Aims Atrial fibrillation (AF) is a frequent co-morbidity in heart failure (HF) associated with increased mortality, but little is known about the mechanisms underlying AF onset in HF patients. We evaluated the association of cardiovascular and genetic risk factors with AF in HF patients. Methods and results Individuals hospitalized for HF (n = 1040; 500 with AF) were identified from a large, population-based cohort study (n = 30 447; 2339 with AF). Genetic polymorphisms in the chromosomal regions 4q25 (rs2200733) and 16q22 (rs2106261) associated with AF in genome-wide association studies were genotyped. Association of cardiovascular risk factors and polymorphisms with AF was tested in HF patients and the entire cohort using both prospective and non-time-dependent models. Cardiovascular risk factors-hypertension, body mass index, sex, smoking, diabetes, and myocardial infarction-were associated with AF in the entire cohort but not in HF patients. In contrast, polymorphisms on chromosomes 16q22 and 4q25 were associated with AF both in the entire cohort and in HF patients, conferring 75% [95% confidence interval (CI) 35-126, P = 2 x 10(-5)] and 57% (95% CI 18-109, P = 0.002) increased risk of AF per copy in HF patients, respectively. In the entire cohort, AF risk in the presence of HF was multiplicatively magnified by genotype for 16q22 (P for interaction = 7 x 10(-4)) but not 4q25 (P = 0.83). In prospective analyses excluding patients with AF diagnosis prior to or simultaneously with HF diagnosis, 16q22 but not 4q25 remained robustly associated with AF (hazard ratio 1.96, 95% CI 1.40-2.73, P = 8 x 10(-5)). The proportion of AF diagnoses in HF patients attributable to polymorphisms was 19% and 12%, respectively. Conclusions A polymorphism in the ZFHX3 gene, encoding a cardiac transcription factor, was associated with increased AF risk in HF patients, and the genetic association with AF was more pronounced in HF patients than in the general population. C1 [Smith, J. Gustav; Platonov, Pyotr G.] Lund Univ, Dept Cardiol, SE-22185 Lund, Sweden. [Smith, J. Gustav; Melander, Olle; Sjogren, Marketa; Hedblad, Bo; Engstrom, Gunnar] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Smith, J. Gustav; Newton-Cheh, Christopher] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Smith, J. Gustav; Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cambridge, MA USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA USA. [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Boston, MA USA. RP Smith, JG (reprint author), Lund Univ, Fac Med, Dept Cardiol, Skane Univ Hosp, SE-22185 Lund, Sweden. EM gustav.smith@med.lu.se OI Engstrom, Gunnar/0000-0002-8618-9152 FU Swedish Cancer Society; Swedish Medical Research Council; Swedish Dairy Association; Albert Pahlsson Foundation; Gunnar Nilsson Foundation; Malmo City Council; Swedish National Health Service; Swedish Heart-Lung Foundation; Lund University; Medical Faculty of Lund University; Skane University Hospital in Malmo; Albert Pahlsson Research Foundation; Crafoord Foundation; Hulda and Conrad Mossfelt Foundation; Ernhold Lundstroms Research Foundation; King Gustaf V and Queen Victoria Fund; Lennart Hanssons Memorial Fund; Marianne and Marcus Wallenberg Foundation; Knut and Alice Wallenberg Foundation; National Institutes of Health [HL080025, HL098283]; Doris Duke Charitable Foundation; Burroughs Wellcome Fund; Lund University Hospital; Craaford Foundation FX The Malmo Diet and Cancer Study was supported by the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Pahlsson and Gunnar Nilsson Foundations, and Malmo City Council. Genotyping was supported by governmental funding of clinical research within the Swedish National Health Service to P.G.P. The Swedish Heart-Lung Foundation (J.G.S.); the Swedish Medical Research Council and Lund University (O.M. and B.H.); the Medical Faculty of Lund University, Skane University Hospital in Malmo, the Albert Pahlsson Research Foundation, the Crafoord Foundation, Swedish National Health Service, the Hulda and Conrad Mossfelt Foundation, the Ernhold Lundstroms Research Foundation, the King Gustaf V and Queen Victoria Fund, the Lennart Hanssons Memorial Fund, the Marianne and Marcus Wallenberg Foundation, and the Knut and Alice Wallenberg Foundation (O.M.); National Institutes of Health (grants HL080025 and HL098283 to C.N.C.); a Doris Duke Charitable Foundation Clinical Scientist Development Award, and a Burroughs Wellcome Fund Career Award for Medical Scientists (C.N-C.); the Swedish National Health Service, Lund University Hospital and the Craaford Foundation (P.G.P.). NR 35 TC 7 Z9 7 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAR PY 2013 VL 15 IS 3 BP 250 EP 257 DI 10.1093/eurjhf/hfs176 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 106RD UT WOS:000316161500004 PM 23132824 ER PT J AU Weiner, RB Baggish, AL Chen-Tournoux, A Marshall, JE Gaggin, HK Bhardwaj, A Mohammed, AA Rehman, SU Barajas, L Barajas, J Gregory, SA Moore, SA Semigran, MJ Januzzi, JL AF Weiner, Rory B. Baggish, Aaron L. Chen-Tournoux, Annabel Marshall, Jane E. Gaggin, Hanna K. Bhardwaj, Anju Mohammed, Asim A. Rehman, Shafiq U. Barajas, Linda Barajas, Justine Gregory, Shawn A. Moore, Stephanie A. Semigran, Marc J. Januzzi, James L., Jr. TI Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Natriuretic peptides; Remodelling; Outcomes ID LEFT-VENTRICULAR DYSFUNCTION; ENZYME-INHIBITOR ENALAPRIL; LONG-TERM PROGRESSION; MYOCARDIAL-INFARCTION; SYSTOLIC DYSFUNCTION; MITRAL REGURGITATION; EUROPEAN-ASSOCIATION; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; OF-CARDIOLOGY AB Aims We sought to determine if heart failure (HF) care with a goal to lower N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations, compared with standard of care (SOC) management, is associated with improvement in echocardiographic parameters of cardiac structure and function. Methods Of 151 subjects with HF due to left ventricular systolic dysfunction (LVSD) prospectively randomized to and results NT-proBNP-guided vs. SOC HF care, 116 had serial echocardiographic data. Endpoints in this echocardiographic study included the relationship between change in NT-proBNP and LV reverse remodelling, as well as associations between biomarker-guided therapy and measures of diastolic function, right ventricular (RV) size and function, estimates of LV filling pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation (MR). After a mean of 10 months of study procedures, in adjusted analyses, final NT-proBNP concentrations predicted risk of remodelling [hazard ratio (HR) up arrow LV end-diastolic volume index = 1.43, 95% confidence interval (CI) 1.10-1.86, P = 0.007; HR up arrow LV end-systolic volume index = 1.54, 95% Cl 1.10-1.91, P = 0.01; HR si,LV ejection fraction (LVEF) = 1.53, 905% CI 1.12-1.89, P = 0.021 In addition to greater improvement in LVEF and reductions in LV volume, compared with SOC, NT-proBNP-guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity (E/E'), pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity. Conclusion NT-proBNP concentrations may serve as a non-invasive indicator of the state of cardiac structure and function in HF due to LVSD. Multiple, prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT-proBNP-guided care vs. SOC. C1 [Weiner, Rory B.; Baggish, Aaron L.; Chen-Tournoux, Annabel; Marshall, Jane E.; Gaggin, Hanna K.; Bhardwaj, Anju; Mohammed, Asim A.; Rehman, Shafiq U.; Barajas, Linda; Barajas, Justine; Gregory, Shawn A.; Moore, Stephanie A.; Semigran, Marc J.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Roche Diagnostics Corporation, Indianapolis, IN; Dennis and Marilyn Barry Cardiology Fellowship; Roman W. Desanctis Clinical Scholar Endowment FX Roche Diagnostics Corporation, Indianapolis, IN (to J.L.J.); the Dennis and Marilyn Barry Cardiology Fellowship (to H.K.G., A.B., A.A.M., and S.U.R.); the Roman W. Desanctis Clinical Scholar Endowment (to J.L.J.). NR 34 TC 17 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAR PY 2013 VL 15 IS 3 BP 342 EP 351 DI 10.1093/eurjhf/hfs180 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 106RD UT WOS:000316161500015 PM 23132825 ER PT J AU Singh, N Eskander, A Huang, SH Curtin, H Bartlett, E Vescan, A Kraus, D O'Sullivan, B Gentili, F Gullane, P Yu, E AF Singh, Navneet Eskander, Antoine Huang, Shao-Hui Curtin, Hugh Bartlett, Eric Vescan, Allan Kraus, Dennis O'Sullivan, Brian Gentili, Fred Gullane, Patrick Yu, Eugene TI Imaging and resectability issues of sinonasal tumors SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE imaging; outcomes; resection; sinonasal tumors ID SQUAMOUS-CELL CARCINOMA; CLINICAL PERINEURAL INVASION; CAROTID-ARTERY INVASION; PARANASAL SINUS TUMORS; ANTERIOR SKULL BASE; MALIGNANT-TUMORS; COMPUTED-TOMOGRAPHY; NECK-CANCER; CRANIOFACIAL RESECTION; PROGNOSTIC-FACTORS AB Sinonasal tumors can invade into the critical structures of the anterior and central skull base. Although the determination of precise tumor histology is difficult with imaging, radiology is important in helping differentiate malignant from benign disease. Imaging helps to map the anatomical extent of intracranial and intraorbital tumor, which has important implications for staging, treatment and prognosis. Imaging also helps to facilitate and plan for craniofacial or endoscopic surgical approaches and radiation planning. This paper will review the locoregional invasion patterns for sinonasal tumors, with emphasis on their imaging features. The authors will discuss the implications for staging, resection potential, choice and details of radiotherapy with or without chemotherapy and prognosis. The imaging assessment of structures and compartments that are critical to the skull base team are highlighted: orbit, cavernous sinus, anterior cranial fossa dura/intracranial tumor, lateral frontal sinus, vascular tumor encasement, perineural tumor spread and tumor effect on the surrounding bony structures. C1 [Singh, Navneet; Bartlett, Eric; Yu, Eugene] Univ Toronto, Fac Med, Dept Med Imaging, Toronto, ON, Canada. [Singh, Navneet; Eskander, Antoine] Univ Toronto, Fac Med, Clinician Investigator Program, Toronto, ON, Canada. [Eskander, Antoine; Bartlett, Eric; Vescan, Allan; O'Sullivan, Brian; Gullane, Patrick; Yu, Eugene] Univ Toronto, Fac Med, Dept Otolaryngol Head & Neck Surg, Toronto, ON, Canada. [Huang, Shao-Hui; O'Sullivan, Brian] Univ Toronto, Dept Radiat Oncol, Princess Margaret Hosp, Toronto, ON, Canada. [Curtin, Hugh] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA USA. [Kraus, Dennis] North Shore LIJ Hlth Syst, New York Head & Neck Inst, New York, NY USA. [Gentili, Fred] Univ Toronto, Dept Surg, Div Neurosurg, Toronto, ON, Canada. RP Yu, E (reprint author), Univ Toronto, Fac Med, Dept Med Imaging, Toronto, ON, Canada. EM eugene.yu@uhn.ca NR 53 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAR PY 2013 VL 13 IS 3 BP 297 EP 312 DI 10.1586/ERA.13.5 PG 16 WC Oncology SC Oncology GA 105FH UT WOS:000316051100014 PM 23477517 ER PT J AU Frantz, S Hofmann, U Fraccarollo, D Schafer, A Kranepuhl, S Hagedorn, I Nieswandt, B Nahrendorf, M Wagner, H Bayer, B Pachel, C Schon, MP Kneitz, S Bobinger, T Weidemann, F Ertl, G Bauersachs, J AF Frantz, Stefan Hofmann, Ulrich Fraccarollo, Daniela Schaefer, Andreas Kranepuhl, Stefanie Hagedorn, Ina Nieswandt, Bernhard Nahrendorf, Matthias Wagner, Helga Bayer, Barbara Pachel, Christina Schoen, Michael P. Kneitz, Susanne Bobinger, Tobias Weidemann, Frank Ertl, Georg Bauersachs, Johann TI Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction SO FASEB JOURNAL LA English DT Article DE extracellular matrix; ischemia; inflammation ID MONOCYTE SUBSETS; MICE; ACTIVATION; EXPRESSION; IMPACT AB Myocardial infarction (MI) leads to rapid necrosis of cardiac myocytes. To achieve tissue integrity and function, inflammatory cells are activated, including monocytes/macrophages. However, the effect of monocyte/macrophage recruitment after MI remains poorly defined. After experimental MI, monocytes and macrophages were depleted through serial injections of clodronate-containing liposomes. Monocyte/macrophage infiltration was reduced in the myocardium after MI by active treatment. Mortality was increased due to thromboembolic events in monocyte-and macrophage-depleted animals (92 vs. 33%; P<0.01). Left ventricular thrombi were detectable as early as 24 h after MI; this was reproduced in a genetic model of monocyte/macrophage ablation. A general prothrombotic state, increased infarct expansion, and deficient neovascularization were not observed. Severely compromised extracellular matrix remodeling (collagen I, placebo liposome vs. clodronate liposome, 2.4 +/- 0.2 vs. 0.8 +/- 0.2 arbitrary units; P<0.001) and locally lost integrity of the endocardium after MI are potential mechanisms. Patients with a left ventricular thrombus had a relative decrease of CD14(+) CD16(+) monocyte/macrophage subsets in the peripheral blood after MI (no thrombus vs. thrombus, 14.2 +/- 0.9 vs. 7.80 +/- 0.4%; P<0.05). In summary, monocytes/macrophages are of central importance for healing after MI. Impaired monocyte/macrophage function appears to be an unrecognized new pathophysiological mechanism for left ventricular thrombus development after MI.-Frantz, S., Hofmann, U., Fraccarollo, D., Schafer, A., Kranepuhl, S., Hagedorn, I., Nieswandt, B., Nahrendorf, M., Wagner, H., Bayer, B., Pachel, C., Schon, M.P., Kneitz, S., Bobinger, T., Weidemann, F., Ertl, G., Bauersachs, J. Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction. FASEB J. 27, 871-881 (2013). www.fasebj.org C1 [Frantz, Stefan; Hofmann, Ulrich; Kranepuhl, Stefanie; Wagner, Helga; Bayer, Barbara; Pachel, Christina; Bobinger, Tobias; Weidemann, Frank; Ertl, Georg] Univ Hosp Wurzburg, Dept Internal Med 1, Rudolf Virchow Ctr, Wurzburg, Germany. [Hagedorn, Ina; Nieswandt, Bernhard] Univ Hosp Wurzburg, Rudolf Virchow Ctr, Dept Vasc Med, Wurzburg, Germany. [Frantz, Stefan; Hofmann, Ulrich; Hagedorn, Ina; Nieswandt, Bernhard; Wagner, Helga; Bayer, Barbara; Pachel, Christina; Weidemann, Frank; Ertl, Georg] Univ Wurzburg, Comprehens Heart Failure Ctr, Microarray Core Facil, D-97080 Wurzburg, Germany. [Kneitz, Susanne] Univ Wurzburg, Interdisciplinary Ctr Clin Res, Microarray Core Facil, D-97080 Wurzburg, Germany. [Fraccarollo, Daniela; Schaefer, Andreas; Bauersachs, Johann] Hannover Med Sch, Dept Cardiol & Angiol, D-30623 Hannover, Germany. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Schoen, Michael P.] Univ Gottingen, Dept Dermatol Venereol & Allergol, D-37073 Gottingen, Germany. RP Frantz, S (reprint author), Univ Wurzburg, Dept Internal Med 1, Univ Hosp Wurzburg, Comprehens Heart Failure Ctr, Oberdurrbacher Str 6, D-97080 Wurzburg, Germany. EM frantz_s@medizin.uni-wuerzburg.de RI Frantz, Stefan/G-1723-2012; OI Schon, Michael/0000-0002-0698-4130 FU Bundesministerium fur Bildung und Forschung [BMBF01 EO1004]; Deutsche Forschungsgemeinschaft [SFB688 TP A10] FX The authors thank Charlotte Dienesch, Benjamin Vogel, Niklas Beyersdorf, Thomas Kerkau, and Jens Biesenbaum for their excellent technical support. This work was supported by grants from the Bundesministerium fur Bildung und Forschung (BMBF01 EO1004; G.E., S.F.) and by the Deutsche Forschungsgemeinschaft (SFB688 TP A10; G.E., S.F.). The authors declare no conflicts of interest. NR 19 TC 48 Z9 53 U1 1 U2 18 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2013 VL 27 IS 3 BP 871 EP 881 DI 10.1096/fj.12-214049 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 098YO UT WOS:000315585200004 PM 23159933 ER PT J AU Lim, TC Rokkappanavar, S Toh, WS Wang, LS Kurisawa, M Spector, M AF Lim, Teck Chuan Rokkappanavar, Swetha Toh, Wei Seong Wang, Li-Shan Kurisawa, Motoichi Spector, Myron TI Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1 alpha release and compatible structural support SO FASEB JOURNAL LA English DT Article DE tissue engineering; cavitary brain lesion; injectable biomaterials; nanoparticles; matrix metalloproteinases ID GROWTH-FACTOR; STEM-CELLS; NEUROBLAST MIGRATION; FACTOR-I; NEUROGENESIS; REGENERATION; NEURONS; STROKE; BRAIN; RAT AB Without chemotactic cues and structural support, cavitary brain lesions typically fail to recruit endogenous neural progenitor cells (NPCs). Toward resolving this, we engineered multifunctional biomaterials comprising injectable gelatin-hydroxyphenylpropionic acid (Gtn-HPA) hydrogels and dextran sulfate/chitosan polyelectrolyte complex nanoparticles (PCNs) that delivered stromal cell-derived factor-1 alpha (SDF-1 alpha). Over 7 d of interface with in vitro tissue simulant containing adult rat hippocampal NPCs (aNPCs) and their neuronal progeny, Gtn-HPA/SDF-1 alpha-PCN hydrogels promoted chemotactic recruitment to enhance infiltration of aNPCs by 3- to 45-fold relative to hydrogels that lacked SDF-1 alpha or vehicles to sustain SDF-1 alpha release. When cross-linked with 0.85-0.95mM H2O2, Gtn-HPA/SDF-1 alpha-PCN hydrogels provided optimally permissive structural support for migration of aNPCs. Specific matrix metalloproteinase (MMP) inhibitors revealed that 42, 30, and 55% of cell migration into Gtn-HPA/SDF-1 alpha-PCN hydrogels involved MMP-2, 3, and 9, respectively, demonstrating the hydrogels to be compatible toward homing endogenous NPCs, given their expression of similar MMPs. Interestingly, PCNs utilized FGF-2 found in situ to induce chemokinesis, potentiate SDF-1 alpha chemotactic recruitment, and increase proliferation of recruited cells, which collectively orchestrated a higher number of migrated aNPCs. Overall, Gtn-HPA/SDF-1 alpha-PCN hydrogels prove to be promising biomaterials for injection into cavitary brain lesions to recruit endogenous NPCs and enhance neural tissue repair/regeneration.-Lim, T. C., Rokkappanavar, S., Toh, W. S., Wang, L.-S., Kurisawa, M., Spector, M. Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1 alpha release and compatible structural support. FASEB J. 27, 1023-1033 (2013). www.fasebj.org C1 [Lim, Teck Chuan; Spector, Myron] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lim, Teck Chuan; Rokkappanavar, Swetha; Toh, Wei Seong; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Rokkappanavar, Swetha; Toh, Wei Seong; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Wang, Li-Shan; Kurisawa, Motoichi] Inst Bioengn & Nanotechnol, Singapore, Singapore. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn Labs, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Wang, Li Shan/F-9460-2013; Toh, Wei Seong/K-7720-2013; KURISAWA, MOTOICHI/C-1325-2014 OI Toh, Wei Seong/0000-0001-9147-6423; KURISAWA, MOTOICHI/0000-0003-2413-6933 FU U.S. Department of Veterans Affairs and Agency for Science, Technology and Research, Singapore FX The authors thank Marsha Doudna Guy for technical assistance and Chyan Ying Ke for critical reading of the manuscript. This work was supported by the Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs and Agency for Science, Technology and Research, Singapore ( to T.C.L., W.S.T., L.W., and M.K.). NR 33 TC 15 Z9 15 U1 2 U2 19 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2013 VL 27 IS 3 BP 1023 EP 1033 DI 10.1096/fj.12-221515 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 098YO UT WOS:000315585200017 PM 23193174 ER PT J AU Iager, AE Kocabas, AM Otu, HH Ruppel, P Langerveld, A Schnarr, P Suarez, M Jarrett, JC Conaghan, J Rosa, GJM Fernandez, E Rawlins, RG Cibelli, JB Crosby, JA AF Iager, Amy E. Kocabas, Arif M. Otu, Hasan H. Ruppel, Patricia Langerveld, Anna Schnarr, Patricia Suarez, Mariluz Jarrett, John C. Conaghan, Joe Rosa, Guilherme J. M. Fernandez, Emilio Rawlins, Richard G. Cibelli, Jose B. Crosby, Javier A. TI Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential SO FERTILITY AND STERILITY LA English DT Article DE Human cumulus cells; gene expression; pregnancy outcome; human oocyte; human embryo ID LUTEINIZING-HORMONE RECEPTOR; DEVELOPMENTAL COMPETENCE; EXPRESSION PROFILES; EMBRYO COMPETENCE; MARKER GENES; FERTILIZATION; INDICATOR; TRANSCRIPTOME; ASSOCIATION; METABOLISM AB Objective: To identify a gene expression signature in human cumulus cells (CCs) predictive of pregnancy outcome across multiple clinics, taking into account the clinic and patient variations inherent in IVF practice. Design: Retrospective analysis of single human cumulus-oocyte complexes with the use of a combined microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) approach. Setting: Multiple private IVF clinics. Patient(s): Fifty-eight patients. Samples from 55 patients underwent qRT-PCR analysis, and samples from 27 patients resulted in live birth. Intervention(s): Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately after oocyte retrieval. Pregnancy prediction analysis used leave-one-out cross-validation with weighted voting. Main Outcome Measure(s): Combinatorial expression of 12 genes in 101 samples from 58 patients. Result(s): We found a set of 12 genes predictive of pregnancy outcome based on their expression levels in CCs. This pregnancy prediction model had an accuracy of 78%, a sensitivity of 72%, a specificity of 84%, a positive predictive value of 81%, and a negative predictive value of 76%. Receiver operating characteristic analysis found an area under the curve of 0.763 +/- 0.079, significantly greater than 0.5 (random chance prediction). Conclusion(s): Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET. (Fertil Steril (R) 2013;99:745-52. (C) 2013 by American Society for Reproductive Medicine.) C1 [Iager, Amy E.; Cibelli, Jose B.] Gema Diagnost, Ann Arbor, MI USA. [Kocabas, Arif M.] Rockefeller Univ, Dev Neurobiol Lab, New York, NY 10021 USA. [Otu, Hasan H.] Harvard Univ, Sch Med, Dept Med, BIDMC Genom Ctr, Boston, MA USA. [Otu, Hasan H.] Istanbul Bilgi Univ, Dept Bioengn, Istanbul, Turkey. [Ruppel, Patricia] Innovat Analyt, Kalamazoo, MI USA. [Langerveld, Anna; Jarrett, John C.] Genemarkers, Kalamazoo, MI USA. [Schnarr, Patricia] Jarrett Fertil Grp, Carmel, IN USA. [Suarez, Mariluz] Stanford Hosp, Stanford Fertil & Reprod Med Ctr, Palo Alto, CA USA. [Conaghan, Joe] Pacific Fertil Ctr, San Francisco, CA USA. [Rosa, Guilherme J. M.] Univ Wisconsin, Dept Anim Sci, Madison, WI USA. [Rosa, Guilherme J. M.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Fernandez, Emilio; Crosby, Javier A.] Clin Las Condes, Unidad Med Reprod, Santiago, Chile. [Rawlins, Richard G.] Rush Univ, Med Ctr, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Cibelli, Jose B.] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. [Cibelli, Jose B.] Michigan State Univ, Dept Anim Sci, E Lansing, MI 48824 USA. [Cibelli, Jose B.] Consejeria Salud, Lab Andaluz Reprogramac Celular LARCEL, Seville, Spain. RP Cibelli, JB (reprint author), B270 Anthony Hall, E Lansing, MI 48823 USA. EM cibelli@msu.edu OI Otu, Hasan/0000-0002-9253-8152; J. M. Rosa, Guilherme/0000-0001-9172-6461 FU Gema Diagnostics FX Supported by Gema Diagnostics. NR 44 TC 20 Z9 21 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2013 VL 99 IS 3 BP 745 EP + DI 10.1016/j.fertnstert.2012.10.041 PG 14 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 098ZZ UT WOS:000315589300026 PM 23200692 ER PT J AU Kung, JTY Colognori, D Lee, JT AF Kung, Johnny T. Y. Colognori, David Lee, Jeannie T. TI Long Noncoding RNAs: Past, Present, and Future SO GENETICS LA English DT Review ID X-CHROMOSOME INACTIVATION; BETA-GLOBIN LOCUS; NATURAL ANTISENSE TRANSCRIPT; EMBRYONIC STEM-CELLS; STEROID-RECEPTOR COACTIVATOR; SMALL INTERFERING RNAS; PROTEIN-CODING GENE; EARLY MOUSE EMBRYOS; MESSENGER-RNA; INTERGENIC TRANSCRIPTION AB Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes. C1 [Kung, Johnny T. Y.; Colognori, David; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Kung, Johnny T. Y.; Colognori, David; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kung, Johnny T. Y.; Colognori, David; Lee, Jeannie T.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU Postgraduate Scholarship from the Natural Sciences and Engineering Research Council of Canada; National Institutes of Health [R01-GM090278] FX We thank members of the laboratory and T. R. Gregory for many helpful discussions, and we apologize to any of our colleagues whose work could not be cited here for space constraints. J.T.Y.K. was supported by a Postgraduate Scholarship from the Natural Sciences and Engineering Research Council of Canada, and J.T.L. is supported by the National Institutes of Health (R01-GM090278). J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 263 TC 275 Z9 301 U1 30 U2 244 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD MAR PY 2013 VL 193 IS 3 BP 651 EP 669 DI 10.1534/genetics.112.146704 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 103MD UT WOS:000315920000001 PM 23463798 ER PT J AU Shi, Z Montgomery, TA Qi, Y Ruvkun, G AF Shi, Zhen Montgomery, Taiowa A. Qi, Yan Ruvkun, Gary TI High-throughput sequencing reveals extraordinary fluidity of miRNA, piRNA, and siRNA pathways in nematodes SO GENOME RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS GENOME; C-ELEGANS; CHROMOSOME SEGREGATION; GENE-EXPRESSION; MICRORNAS; GERMLINE; RNA; 21U-RNAS; SCALE; SPERMATOGENESIS AB The nematode Caenorhabditis elegans contains each of the broad classes of eukaryotic small RNAs, including microRNAs (miRNAs), endogenous small-interfering RNAs (endo-siRNAs), and piwi-interacting RNAs (piRNAs). To better understand the evolution of these regulatory RNAs, we deep-sequenced small RNAs from C. elegans and three closely related nematodes: C. briggsae, C. remanei, and C. brenneri. The results reveal a fluid landscape of small RNA pathways with essentially no conservation of individual sequences aside from a subset of miRNAs. We identified 54 miRNA families that are conserved in each of the four species, as well as numerous miRNAs that are species-specific or shared between only two or three species. Despite a lack of conservation of individual piRNAs and siRNAs, many of the features of each pathway are conserved between the different species. We show that the genomic distribution of 26G siRNAs and the tendency for piRNAs to cluster is conserved between C. briggsae and C. elegans. We also show that, in each species, 26G siRNAs trigger stage-specific secondary siRNA formation. piRNAs in each species also trigger secondary siRNA formation from targets containing up to three mismatches. Finally, we show that the production of male-and female-specific piRNAs is conserved in all four species, suggesting distinct roles for piRNAs in male and female germlines. C1 [Shi, Zhen; Montgomery, Taiowa A.; Qi, Yan; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Shi, Zhen] Harvard Univ, Sch Med, Biol Sci Dent Med Program, Boston, MA 02115 USA. [Montgomery, Taiowa A.; Qi, Yan; 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 Montgomery, Taiowa/0000-0001-7857-3253 FU American Heart Association; Damon Runyon Cancer Research Foundation [DRG 2029-09]; Massachusetts General Hospital Executive Committee of Research Tosteson; Ellison Medical Foundation/AFAR; Life Sciences Research Foundation; NIH [R01-GM44619] FX We thank the Ruvkun lab members for constructive suggestions and thoughtful critiques of the work. We thank Allison Billi, Mallory Freeberg, and John Kim for sharing unpublished information. We thank the Caenorhabditis Genetics Center (CGC) for worm strains. Z.S. is supported by an American Heart Association predoctoral fellowship. T.A.M. was supported by the Damon Runyon Cancer Research Foundation (DRG 2029-09) and is a Massachusetts General Hospital Executive Committee of Research Tosteson postdoctoral fellow. Y.Q. is an Ellison Medical Foundation/AFAR postdoctoral fellow supported by the Life Sciences Research Foundation. This work was supported by a grant from the NIH to G.R. (R01-GM44619). NR 50 TC 20 Z9 319 U1 1 U2 36 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAR PY 2013 VL 23 IS 3 BP 497 EP 508 DI 10.1101/gr.149112.112 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 101XD UT WOS:000315806800009 PM 23363624 ER PT J AU Gheorghiade, M Vaduganathan, M Ambrosy, A Bohm, M Campia, U Cleland, JGF Fedele, F Fonarow, GC Maggioni, AP Mebazaa, A Mehra, M Metra, M Nodari, S Pang, PS Ponikowski, P Sabbah, HN Komajda, M Butler, J AF Gheorghiade, Mihai Vaduganathan, Muthiah Ambrosy, Andrew Boehm, Michael Campia, Umberto Cleland, John G. F. Fedele, Francesco Fonarow, Gregg C. Maggioni, Aldo P. Mebazaa, Alexandre Mehra, Mandeep Metra, Marco Nodari, Savina Pang, Peter S. Ponikowski, Piotr Sabbah, Hani N. Komajda, Michel Butler, Javed TI Current management and future directions for the treatment of patients hospitalized for heart failure with low blood pressure SO HEART FAILURE REVIEWS LA English DT Article DE Heart failure; Blood pressure; Epidemiology; Hemodynamics; Outcomes ID CORONARY-ARTERY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; LEFT-VENTRICULAR SHAPE; FUNCTIONAL MITRAL REGURGITATION; NATIONAL REGISTRY ADHERE; WORSENING RENAL-FUNCTION; IDIOPATHIC DILATED CARDIOMYOPATHY; INITIATE LIFESAVING TREATMENT; ACUTE MYOCARDIAL-INFARCTION; INTENSIVE-CARE MEDICINE AB Although patients hospitalized with heart failure have relatively low in-hospital mortality, the post-discharge rehospitalization and mortality rates remain high despite advances in treatment. Most patients admitted for heart failure have normal or high blood pressure, but 15-25 % have low systolic blood pressure with or without signs and/or symptoms of hypoperfusion. All pharmacological agents known to improve the prognosis of patients with heart failure also reduce blood pressure, and this limits their use in patients with heart failure and low blood pressure (HF-LBP). However, patients with HF-LBP have much higher in-hospital and post-discharge mortality. In these patients, a conceptually important therapeutic target is to improve cardiac output in order to alleviate signs of hypoperfusion. Accordingly, the majority of these patients will require an inotrope as cardiac dysfunction is the cause of their low cardiac output. However, the short-term use of currently available inotropes has been associated with further decreases in blood pressure and increases in heart rate, myocardial oxygen consumption and arrhythmias. Agents that improve cardiac contractility without this undesirable effects should be developed. To the best of our knowledge, the epidemiology, pathophysiology and therapy of patients with HF-LBP have not been addressed thoroughly. In June 2010, a workshop that included scientists and clinicians was held in Rome, Italy. The objectives of this meeting were to (1) develop a working definition for HF-LBP, (2) describe its clinical characteristics and pathophysiology, (3) review current therapies and their limitations, (4) discuss novel agents in development and (5) create a framework for the design and conduct of future clinical trials. C1 [Gheorghiade, Mihai; Campia, Umberto; Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ambrosy, Andrew] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Boehm, Michael] Univ Hosp Saarland, Dept Internal Med 3, Homburg, Germany. [Cleland, John G. F.] Univ Hull, Hull York Med Sch, Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England. [Fedele, Francesco] Univ Roma La Sapienza, Dept Cardiovasc Resp & Morphol Sci, Rome, Italy. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Mebazaa, Alexandre] Univ Paris, Dept Anesthesia & Intens Care, Lariboisiere Hosp, F-75252 Paris, France. [Mehra, Mandeep] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Metra, Marco; Nodari, Savina] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [Metra, Marco; Nodari, Savina] Civil Hosp Brescia, Brescia, Italy. [Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Ponikowski, Piotr] Wroclaw Med Univ, Dept Cardiol, Wroclaw, Poland. [Sabbah, Hani N.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Komajda, Michel] Univ Paris 06, AP HP, Paris, France. [Butler, Javed] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 North Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Ponikowski, Piotr/O-6454-2015; OI Campia, Umberto/0000-0002-7894-3565; Cleland, John/0000-0002-1471-7016; Maggioni, Aldo Pietro/0000-0003-2764-6779; Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Mehra, Mandeep/0000-0001-8683-7044 FU Boehringer-Ingelheim; Servier; Pfizer; Medtronic; National Institutes of Health [K12-HL083790]; National Heart Lung and Blood Institute, National Institutes of Health; Abbott; Bayer Healthcare AG; Johnson Johnson; Stealth Peptides; Sigma Tau; GE Healthcare FX Mihai Gheorghiade MD: consultant-Abbott Laboratories (modest), Astellas (modest), Astra Zeneca (modest), Bayer Schering Pharma AG (significant), CorThera, Inc. (modest), Cytokinetics, Inc. (modest), DebioPharm SA (significant), Errekappa Terapeutici (Milan, Italy) (modest), GlaxoSmithKline (modest), Johnson & Johnson (modest), Medtronic (significant), Merck (modest), Novartis Pharma AG (significant), Otsuka Pharmaceuticals (significant), Pericor Therapeutics (significant), Protein Design Laboratories (modest), Sanofi-Aventis (modest), Sigma Tau (significant), Solvay Pharmaceuticals (significant); Muthiah Vaduganathan MD MPH: none; Andrew Ambrosy MD: none; Michael Boehm MD PhD: support by Boehringer-Ingelheim, Servier, Pfizer, Medtronic; Umberto Campia MD: supported by a National Institutes of Health grant (K12-HL083790); John GF Cleland MD: received an honorarium from Bayer for an advisory board. Funding level modest; Francesco Fedele MD: none; Gregg C. Fonarow MD: consultant for Novartis, Medtronic and Takeda; Aldo P. Maggioni MD: none; Alexandre Mebazaa MD: honoraria from Orion, Alere, Thermofisher and Bayer and consultant for Bayer Pharma; Mandeep Mehra MD: consultant for Johnson & Johnson, Medtronics, St. Judes Inc. Research support, National Heart Lung and Blood Institute, National Institutes of Health; Marco Metra MD: honoraria and advisory board from Bayer and Novartis. Modest funding level; Savina Nodari MD: none; Peter S. Pang MD: consultant for Bayer, Medtronic, Novartis, Otsuka, Sigma Tau, Trevena, honoraria from Johnson & Johnson, the Medicines Company and Corthera, and research support from Abbott; Piotr Ponikowski MD: consultant to Bayer Schering AG, Corthera, Amgen, Johnson & Johnson; Hani N. Sabbah PhD: research grants from Bayer Healthcare AG, Johnson & Johnson, Stealth Peptides, Sigma Tau. Consultant to Bayer Healthcare AG and Johnson and Johnson; Michel Komajda MD: none; Javed Butler MD MPH: consultant to Cardiomems, Trevena, Bayer Healthcare, Takeda and Amgen. Events Committee for WorldHeart and Corthera. Research support by GE Healthcare, Medtronic, National Heart Lung and Blood Institute, National Institutes of Health. NR 104 TC 17 Z9 17 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 J9 HEART FAIL REV JI Heart Fail. Rev. PD MAR PY 2013 VL 18 IS 2 BP 107 EP 122 DI 10.1007/s10741-012-9315-1 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 105OW UT WOS:000316082600001 PM 22581217 ER PT J AU Brandimarte, F Vaduganathan, M Mureddu, GF Cacciatore, G Sabbah, HN Fonarow, GC Goldsmith, SR Butler, J Fedele, F Gheorghiade, M AF Brandimarte, Filippo Vaduganathan, Muthiah Mureddu, Gian Francesco Cacciatore, Giuseppe Sabbah, Hani N. Fonarow, Gregg C. Goldsmith, Steven R. Butler, Javed Fedele, Francesco Gheorghiade, Mihai TI Prognostic implications of renal dysfunction in patients hospitalized with heart failure: data from the last decade of clinical investigations SO HEART FAILURE REVIEWS LA English DT Article DE Heart failure; Renal function; Prognosis; Mortality; Hospitalizations ID CORONARY-ARTERY-DISEASE; BLOOD UREA NITROGEN; ACUTE KIDNEY INJURY; LONG-TERM OUTCOMES; CARDIORENAL SYNDROME; IMPACT; RISK; INSUFFICIENCY; POPULATION; ADMISSION AB Numerous studies over the last decade have demonstrated that renal dysfunction and worsening renal function (WRF) are common in patients hospitalized for heart failure (HHF) and appear to be associated with poor in-hospital and post-discharge outcomes. Unfortunately, its etiology has not been completely understood, and its prediction during hospitalization remains challenging. The evaluation of renal impairment during hospitalization should take into consideration the underlying renal substrate (e.g., predisposing clinical comorbidities such as diabetes and hypertension), initiating mechanisms (e.g., in-hospital therapies such as diuretics), and amplifying factors (neurohormonal and hemodynamic profile changes). Various patterns of WRF may have different prognostic implications and may require different therapeutic approaches. WRF may be initially classified by duration (transient vs. persistent) and by etiology (elevated venous pressures vs. arterial underfilling). Other critical contributing factors during hospitalization include progressive left ventricular dysfunction, neurohormonal activation, and medications. Transient WRF as a result of aggressive therapy targeting congestion may not be associated with poor outcomes. Persistent WRF seen in patients with severe hemodynamic derangements may be associated with poor post-discharge prognosis. Future investigations must clarify the pathophysiological correlates of various patterns of WRF. To date, there is an unmet clinical need to achieve adequate control over congestion while preserving renal function in HHF patients. Thus, the aim of this review is to provide an in-depth and critical interpretation of the available data on the prognostic importance of RD and WRF during hospitalization in an effort to improve HF management. C1 [Brandimarte, Filippo; Mureddu, Gian Francesco; Cacciatore, Giuseppe] San Giovanni Addolorata Community Hosp, Dept Cardiovasc Dis, Rome, Italy. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sabbah, Hani N.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Goldsmith, Steven R.] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Butler, Javed] Emory Clin Cardiovasc Res Inst, Atlanta, GA USA. [Fedele, Francesco] Univ Roma La Sapienza, Dept Cardiovasc Resp Nephrol & Geriatr Dis, Rome, Italy. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. RP Brandimarte, F (reprint author), San Giovanni Addolorata Community Hosp, Dept Cardiovasc Dis, Rome, Italy. EM brandimarte.filippo@gmail.com FU Bayer Healthcare AG; Johnson and Johnson; Stealth Peptides; Sigma Tau; Events Committee for WorldHeart; Corthera; GE Healthcare, Medtronic; National Heart Lung and Blood Institute, National Institutes of Health FX Conflict of interest Filippo Brandimarte, MD: None; Muthiah Vaduganathan, MD MPH: None; Gian francesco Mureddu, MD: None; Giuseppe Cacciatore, MD: None; Hani N. Sabbah, PhD: Research Grants from Bayer Healthcare AG, Johnson and Johnson, Stealth Peptides, Sigma Tau, Consultant to Bayer Healthcare AG, and Johnson and Johnson; Gregg C. Fonarow, MD: Consultant for Novartis, Medtronic, and Takeda; Steven R. Goldsmith, MD: Consultant for Astellas and Otsuka; Javed Butler, MD MPH: Consultant to Cardiomems, Trevena, Bayer Healthcare, Takeda, and Amgen; Events Committee for WorldHeart and Corthera, Research Support, GE Healthcare, Medtronic, National Heart Lung and Blood Institute, National Institutes of Health; Francesco Fedele, MD: None; Mihai Gheorghiade, MD: Consultant - Abbott Laboratories (modest), Astellas (modest), Astra Zeneca (modest), Bayer Schering Pharma AG (significant), CorThera, Inc (modest), Cytokinetics, Inc (modest), DebioPharm SA (significant), Errekappa Terapeutici (Milan, Italy) (modest), GlaxoSmithKline (modest), Johnson & Johnson (modest), Medtronic (significant), Merck (modest), Novartis Pharma AG (significant), Otsuka Pharmaceuticals (significant), Pericor Therapeutics (significant), Protein Design Laboratories (modest), Sanofi-Aventis (modest), Sigma Tau (significant), Solvay Pharmaceuticals (significant). NR 51 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 J9 HEART FAIL REV JI Heart Fail. Rev. PD MAR PY 2013 VL 18 IS 2 BP 167 EP 176 DI 10.1007/s10741-012-9317-z PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 105OW UT WOS:000316082600006 PM 22572909 ER PT J AU Deo, R Nalls, MA Avery, CL Smith, JG Evans, DS Keller, MF Butler, AM Buxbaum, SG Li, G Quibrera, PM Smith, EN Tanaka, T Akylbekova, EL Alonso, A Arking, DE Benjamin, EJ Berenson, GS Bis, JC Chen, LY Chen, W Cummings, SR Ellinor, PT Evans, MK Ferrucci, L Fox, ER Heckbert, SR Heiss, G Hsueh, WC Kerr, KF Limacher, MC Liu, Y Lubitz, SA Magnani, JW Mehra, R Marcus, GM Murray, SS Newman, AB Njajou, O North, KE Paltoo, DN Psaty, BM Redline, SS Reiner, AP Robinson, JG Rotter, JI Samdarshi, TE Schnabel, RB Schork, NJ Singleton, AB Siscovick, D Soliman, EZ Sotoodehnia, N Srinivasan, SR Taylor, HA Trevisan, M Zhang, Z Zonderman, AB Newton-Cheh, C Whitsel, EA AF Deo, R. Nalls, M. A. Avery, C. L. Smith, J. G. Evans, D. S. Keller, M. F. Butler, A. M. Buxbaum, S. G. Li, G. Quibrera, P. Miguel Smith, E. N. Tanaka, T. Akylbekova, E. L. Alonso, A. Arking, D. E. Benjamin, E. J. Berenson, G. S. Bis, J. C. Chen, L. Y. Chen, W. Cummings, S. R. Ellinor, P. T. Evans, M. K. Ferrucci, L. Fox, E. R. Heckbert, S. R. Heiss, G. Hsueh, W. C. Kerr, K. F. Limacher, M. C. Liu, Y. Lubitz, S. A. Magnani, J. W. Mehra, R. Marcus, G. M. Murray, S. S. Newman, A. B. Njajou, O. North, K. E. Paltoo, D. N. Psaty, B. M. Redline, S. S. Reiner, A. P. Robinson, J. G. Rotter, J. I. Samdarshi, T. E. Schnabel, R. B. Schork, N. J. Singleton, A. B. Siscovick, D. Soliman, E. Z. Sotoodehnia, N. Srinivasan, S. R. Taylor, H. A. Trevisan, M. Zhang, Z. Zonderman, A. B. Newton-Cheh, C. Whitsel, E. A. TI Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants SO HEART RHYTHM LA English DT Article DE African Americans; Heart rate; Singe nucleotide polymorphisms; Meta-analysis ID SICK SINUS SYNDROME; MIDDLE-AGED MEN; RISK-FACTOR; FOLLOW-UP; POPULATIONS; MORTALITY; DISEASE; CONDUCTION; VARIANTS; MICE AB BACKGROUND Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE To identify novel genetic variants associated with resting heart rate in African Americans. METHODS Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of singe nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P <= 2.5 x 10(-8)). RESULTS Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98 x 10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin. C1 [Deo, R.] Univ Penn, Div Cardiol, Electrophysiol Sect, Philadelphia, PA 19104 USA. [Nalls, M. A.; Keller, M. F.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Avery, C. L.; Whitsel, E. A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Smith, J. G.] Lund Univ, Fac Med, Dept Cardiol, Lund, Sweden. [Smith, J. G.; Newton-Cheh, C.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA. [Evans, D. S.; Cummings, S. R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Keller, M. F.] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA. [Butler, A. M.; Quibrera, P. Miguel; Heiss, G.; North, K. E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Buxbaum, S. G.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA. [Buxbaum, S. G.] Jackson State Univ, Sch Hlth Sci, Dept Epidemiol & Biostat, Jackson, MS USA. [Li, G.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Smith, E. N.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. [Smith, E. N.] Univ Calif San Diego, Sch Med, Radys Childrens Hosp, La Jolla, CA 92093 USA. [Tanaka, T.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Akylbekova, E. L.; Fox, E. R.; Taylor, H. A.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Alonso, A.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Arking, D. E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Benjamin, E. J.] NHLBI, Framingham Study, Framingham, MA USA. [Benjamin, E. J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, E. J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, E. J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Benjamin, E. J.] Boton Univ, Evans Mem Whitaker Cardiovasc Inst, Boston, MA USA. [Berenson, G. S.; Chen, W.; Srinivasan, S. R.] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Bis, J. C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Chen, L. Y.] Univ Minnesota, Sch Med, Div Cardiovasc, Cardiac Arrhythmia Ctr, Minneapolis, MN 55455 USA. [Ellinor, P. T.; Lubitz, S. A.; Newton-Cheh, C.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, P. T.; Lubitz, S. A.; Newton-Cheh, C.] Harvard Univ, Sch Med, Boston, MA USA. [Ellinor, P. T.; Newton-Cheh, C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Evans, M. K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Ferrucci, L.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Heckbert, S. R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Hsueh, W. C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kerr, K. F.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Limacher, M. C.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA. [Liu, Y.] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Magnani, J. W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Magnani, J. W.] NHLBI, Framingham, MA USA. [Magnani, J. W.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Mehra, R.] Case Western Sch Med, Dept Med, Cleveland, OH USA. [Marcus, G. M.] Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, San Francisco, CA USA. [Murray, S. S.; Schork, N. J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Murray, S. S.; Schork, N. J.] Scripps Res Inst, La Jolla, CA 92037 USA. [Newman, A. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Njajou, O.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [North, K. E.] Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Paltoo, D. N.] NIH, Off Sci Policy, Off Director, Bethesda, MD 20892 USA. [Psaty, B. M.; Siscovick, D.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, B. M.; Siscovick, D.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Redline, S. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med,Dept Hlth, Boston, MA 02115 USA. [Reiner, A. P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Robinson, J. G.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Rotter, J. I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Samdarshi, T. E.] Univ Mississippi, Sch Med, Jackson, MS 39216 USA. [Schnabel, R. B.] Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Singleton, A. B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Soliman, E. Z.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA. [Sotoodehnia, N.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Taylor, H. A.] Univ Mississippi, Med Ctr, Dept Epidemiol, Jackson, MS 39216 USA. [Taylor, H. A.] Univ Mississippi, Med Ctr, Dept Prevent Med, Jackson, MS 39216 USA. [Trevisan, M.] CUNY City Coll, Sophie Davis Sch Biomed Educ, New York, NY USA. [Zhang, Z.] Wake Forest Sch Med, Epidemiol Cardiol Ctr EPICARE, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Zonderman, A. B.] NIA, Bethesda, MD 20892 USA. [Zonderman, A. B.] NIH Biomed Res Ctr, NIH Intramural Res Program, Baltimore, MD USA. [Whitsel, E. A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Deo, R (reprint author), Univ Penn, Div Cardiol, Electrophysiol Sect, 3400 Spruce St, Philadelphia, PA 19104 USA. EM Rajat.Deo@uphs.upenn.edu RI Singleton, Andrew/C-3010-2009; Alonso, Alvaro/A-4917-2010; Schnabel, Renate/F-6527-2014; Newman, Anne/C-6408-2013; Kerr, Kathleen/A-2893-2013; Buxbaum, Sarah/E-1970-2013; OI Zonderman, Alan B/0000-0002-6523-4778; Alonso, Alvaro/0000-0002-2225-8323; Newman, Anne/0000-0002-0106-1150; Buxbaum, Sarah/0000-0002-4886-3564; Mehra, Reena/0000-0002-6222-2675; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015]; Baylor Medical College [N01-HC-55016]; University of Mississippi Medical Center [N01-HC-55021]; University of Minnesota [N01-HC-55019]; Johns Hopkins University [N01-HC-55020]; University of Texas, Houston [N01-HC-55022]; University of North Carolina, Forsyth County [N01-HC-55018]; National Institutes of Health (NIB), National Institute on Aging (NIA); MedStar Research Institute; NIH/National Center for Research Resources (NCRR) [UL1 RR025774]; Scripps Genomic Medicine; National Institute of Child Health and Human Development [HD-061437, HD-062783]; NIA [AG-16592, AG-023629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756, HL085251, N02-HL-64278]; National Institute of Neurological Disorders and Stroke (NINDS); National Center of Advancing Translational Technologies CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; NIH [HHSN268200782096C, K23DK089118]; NIH, NIA; National Center on Minority Health and Health Disparities [Z01-AG000513, 2009-149]; NIH by the NHLIB [N01-HC-95170, N01-HC-95171, N01-HC-95172]; National Center for Minority Health and Health Disparities; NHLBI, NIH, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; NIH/NIEHS [1-R01-ES017794]; NIH/NCI [N01-WH-2-2110]; NHLBI/NIH [R00HL098458]; Swedish Heart-Lung Foundation; [NIB HL 46380]; [M01RR00080]; [N01-HC-95159]; [N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95168]; [N01-HC95163]; [N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167]; [N01-HC-95169]; [R01-HL-071205] FX The first 5 authors should be regarded as first authors. Atherosclerosis Risk in Communities (ARIC): The ARIC study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts to the University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55022), and University of North Carolina, Forsyth County (N01-HC-55018). Baltimore Longitudinal Study of Aging (BLSA): The BLSA was supported in part by the Intramural Research Program of the National Institutes of Health (NIB), National Institute on Aging (NIA). A portion of that support was through an R&D contract with MedStar Research Institute. Bogalusa Heart Study (BHS): Dr Smith, Dr Murray, and Dr Schork were supported in part by NIH/National Center for Research Resources (NCRR) grant number UL1 RR025774 and Scripps Genomic Medicine. The BHS was supported by grants HD-061437 and HD-062783 from the National Institute of Child Health and Human Development and AG-16592 from the NIA. Cleveland Family Study (CFS): This study was supported by grant to Case Western Reserve University (NIB HL 46380, M01RR00080). Cardiovascular Health Study (CHS): This CHS research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, and HHSN268201200036C and NHLBI grants HL080295, HL087652, HL105756, and HL085251 with additional contribution from National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping were supported in part by National Center of Advancing Translational Technologies CTSI grant UL1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Health, Aging, and Body Composition (Health ABC) study: The Health ABC study was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the NIH to Johns Hopkins University (contract number HHSN268200782096C). This research was supported in part by the Intramural Research Program of the NIH, NIA. The Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study: This HANDLS study was supported by the Intramural Research Program of the NIH, NIA, and the National Center on Minority Health and Health Disparities (contract number Z01-AG000513 and human subjects protocol number 2009-149). Data analyses for the HANDLS study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (http://biowulf.nih.gov). Jackson Heart Study (JHS): This JHS was supported by NIH contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172 provided by the NHLIB and the National Center for Minority Health and Health Disparities.; Multi-Ethnic Study of Atherosclerosis (MESA): This study was supported by grants to the University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC-95169), Cedars-Sinai Medical Center (R01-HL-071205), and University of Virginia (subcontract to R01-HL-071205). Women's Health Initiative (WHI): The WHI program is funded by the NHLBI, NIH, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. This article was prepared in collaboration with the investigators of WHI and has been reviewed and/or approved by WHI. WHI investigators are listed at http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf. Funding for WHI SHARe genotyping was provided by NHLBI contract N02-HL-64278. Analyses in WHI were funded by the NIH/NIEHS (1-R01-ES017794, Whitsel) and the NIH/NCI (N01-WH-2-2110, North). Dr Deo was supported by K23DK089118 from the NIH. Dr Avery was partially supported by NHLBI/NIH grant R00HL098458. Dr Smith was supported by the Swedish Heart-Lung Foundation. Address reprint requests and correspondence: Dr Rajat Deo, Division of Cardiology, Electrophysiology Section, University of Pennsylvania, 3400 Spruce St, 9 Founders Cardiology, Philadelphia, PA 19104. E-mail address: Rajat.Deo@uphs.upenn.edu. NR 35 TC 10 Z9 10 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2013 VL 10 IS 3 BP 401 EP 408 DI 10.1016/j.hrthm.2012.11.014 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101KD UT WOS:000315773000017 PM 23183192 ER PT J AU Jain, A Singh, JA AF Jain, Archana Singh, Jasvinder A. TI Harms of TNF inhibitors in rheumatic diseases: a focused review of the literature SO IMMUNOTHERAPY LA English DT Review DE adverse effect; biologic; harm; rheumatic disease; rheumatoid arthritis; TNF biologic; TNF inhibitor ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA ANTAGONISTS; SERIOUS BACTERIAL-INFECTIONS; MODIFYING ANTIRHEUMATIC DRUGS; RANDOMIZED CONTROLLED-TRIALS; DAILY CLINICAL-PRACTICE; FACTOR THERAPY; BIOLOGICS-REGISTER; BRITISH-SOCIETY; HEART-FAILURE AB A focused review of the risk of harms of anti-TNF inhibitors in adult rheumatic diseases was performed. An increased risk of serious infections, tuberculosis and other opportunistic infections has been reported across various studies, with etanercept appearing to have a modestly better safety profile in terms of tuberculosis and opportunistic infections, and infliximab posing a higher risk of serious infections. Evidence suggests no increase in risk of cancer with anti-TNF biologics, but there is an increased risk of non-melanoma skin cancer. Elderly patients appear to be at increased risk of incident or worsening heart failure with anti-TNF biologic use. C1 [Jain, Archana; 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.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Takeda; Savient; URL pharmaceuticals; Ardea; Novartis; Allergan FX JA Singh has received research and travel grants from Takeda and Savient; and consultant fees from URL pharmaceuticals, Savient, Takeda, Ardea, Novartis and Allergan. 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 81 TC 28 Z9 29 U1 0 U2 15 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD MAR PY 2013 VL 5 IS 3 BP 265 EP 299 DI 10.2217/IMT.13.10 PG 35 WC Immunology SC Immunology GA 100LU UT WOS:000315703500012 PM 23444956 ER PT J AU Patel, AB Dhande, LA Pusdekar, YV Borkar, JA Badhoniya, NB Hibberd, PL AF Patel, Archana B. Dhande, Leena A. Pusdekar, Yamini V. Borkar, Jitesh A. Badhoniya, Neetu B. Hibberd, Patricia L. TI Childhood illness in households using biomass fuels in India: secondary data analysis of nationally representative national family health surveys SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE Indoor air pollution; Biomass; Solid fuels; Respiratory infection; Diarrhea; Fever; Under nutrition; India ID INDOOR AIR-POLLUTION; DEVELOPING-COUNTRIES; BIRTH-WEIGHT; EXPOSURE; CHILDREN; SMOKE; PNEUMONIA; MORTALITY; GUATEMALA; RISK AB Background: Half of the world's population uses solid fuels for energy and cooking, resulting in 1.5 million deaths annually, approximately one-third of which occur in India. Most deaths are linked to childhood pneumonia or acute lower respiratory tract infection (ALRI), conditions that are difficult to diagnose. The overall effect of biomass combustion on childhood illness is unclear. Objectives: To evaluate whether type of household fuel is associated with symptoms of ALRI (cough and difficulty breathing), diarrhea or fever in children aged 0-36 months. Methods: We analyzed nationally representative samples of households with children aged 0-36 months from three national family health surveys conducted between 1992 and 2006 in India. Households were categorized as using low (liquid petroleum gas/electricity), medium (coal/kerosene) or high polluting fuel (predominantly wood/agricultural waste). Odds ratios adjusted for confounders for exposure to high and medium polluting fuel were compared with low polluting fuel (LPF). Results: Use of high polluting fuel (HPF) in India changed minimally (82 to 78 %), although LPF use increased from 8% to 18%. HPF was consistently associated with ALRI [ adjusted odds ratio (95% confidence interval) 1.48 (1.08-2.03) in 1992-3; 1.54 (1.33-1.77) in 1998-9; and 1.53 (1.21-1.93) in 2005-6). Fever was associated with HPF in the first two surveys but not in the third survey. Diarrhea was not consistently associated with HPF. Conclusions: There is an urgent need to increase the use of LPF or equivalent clean household fuel to reduce the burden of childhood illness associated with IAP in India. C1 [Patel, Archana B.; Dhande, Leena A.; Pusdekar, Yamini V.; Borkar, Jitesh A.; Badhoniya, Neetu B.] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Patel, Archana B.; Dhande, Leena A.] Indira Gandhi Govt Med Coll, Dept Pediat, Nagpur, Maharashtra, India. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. RP Patel, AB (reprint author), Kinkinie Grover Mem Charitable Trust, Lata Med Res Fdn, 9-1 Kinkinie Kutir,Near Deeksha Bhoomi Sq, Nagpur 440022, Maharashtra, India. EM dr_apatel@yahoo.com FU National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health [U01-HD 058322, K24-AT003683] FX This publication was made possible in part by funding obtained (grant nos. U01-HD 058322 and K24-AT003683) from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health. We also acknowledge editorial support of Lauren Kleimola. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCCAM. NR 27 TC 3 Z9 3 U1 0 U2 8 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD MAR PY 2013 VL 19 IS 1 BP 35 EP 42 DI 10.1179/2049396712Y.0000000013 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 104PS UT WOS:000316007300005 PM 23582613 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Coronary Plaque Erosion Recognition and Management SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE optical coherence tomography; plaque rupture; STEMI ID ACUTE MYOCARDIAL-INFARCTION; ATHEROSCLEROTIC PLAQUES; THROMBOSIS; MORPHOLOGY; RUPTURE C1 [Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 8 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2013 VL 6 IS 3 BP 288 EP 289 DI 10.1016/j.jcmg.2013.01.003 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 103SN UT WOS:000315939300002 PM 23473110 ER PT J AU Douglas, PS Picard, MH AF Douglas, Pamela S. Picard, Michael H. TI Healthcare Reform for Imagers Finding a Way Forward Now SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE access; cost; health care reform; leadership; quality ID CT ANGIOGRAPHY; THINK-TANK; QUALITY; COLLEGE; HEART AB The changing healthcare environment presents many challenges to cardiovascular imagers. This perspective paper uses current trends to propose strategies that cardiovascular imagers can follow to lead in managing change and developing the imaging laboratory of the future. In the area of quality, imagers are encouraged to follow guidelines and standards, implement structured reporting and laboratory databases, adopt ongoing quality improvement programs, and use benchmarks to confirm imaging quality. In the area of access, imagers are encouraged to enhance availability of testing, focus on patient and referring physician value and satisfaction, collaboratively implement new technologies and uses of imaging, integrate health information technology in the laboratory, and work toward the appropriate inclusion of imaging in new healthcare delivery models. In the area of cost, imagers are encouraged to minimize laboratory operating expenses without compromising quality, and to take an active role in care redesign initiatives to ensure that imaging is utilized appropriately and at proper time intervals. Imagers are also encouraged to learn leadership and management skills, undertake strategic planning exercises, and build strong, collaborative teams. Although it is difficult to predict the future of cardiovascular imaging delivery, a reasonable sense of the likely direction of many changes and careful attention to the fundamentals of good health care (quality, access, and cost) can help imagers to thrive now and in the future. C1 [Douglas, Pamela S.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Douglas, PS (reprint author), 7022 North Pavil DUMC,POB 17969, Durham, NC 27715 USA. EM pamela.douglas@duke.edu OI Picard, Michael/0000-0002-9264-3243 NR 16 TC 4 Z9 4 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2013 VL 6 IS 3 BP 385 EP 391 DI 10.1016/j.jcmg.2012.10.009 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 103SN UT WOS:000315939300015 PM 23219412 ER PT J AU Beckett, EL Stevens, RL Jarnicki, AG Kim, RY Hanish, I Hansbro, NG Deane, A Keely, S Horvat, JC Yang, M Oliver, BG van Rooijen, N Inman, MD Adachi, R Soberman, RJ Hamadi, S Wark, PA Foster, PS Hansbro, PM AF Beckett, Emma L. Stevens, Richard L. Jarnicki, Andrew G. Kim, Richard Y. Hanish, Irwan Hansbro, Nicole G. Deane, Andrew Keely, Simon Horvat, Jay C. Yang, Ming Oliver, Brian G. van Rooijen, Nico Inman, Mark D. Adachi, Roberto Soberman, Roy J. Hamadi, Sahar Wark, Peter A. Foster, Paul S. Hansbro, Philip M. TI A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Cigarette smoke; chronic obstructive pulmonary disease; inflammation; emphysema; airway remodeling; lung function; macrophage; mast cell; protease; mouse mast cell protease 6; htryptase-beta ID ALLERGIC AIRWAYS DISEASE; SMOKE-INDUCED EMPHYSEMA; REGULATORY T-CELLS; STREPTOCOCCUS-PNEUMONIAE; INFLAMMATORY ARTHRITIS; RESPIRATORY-INFECTION; TGF-BETA; ASTHMA; COPD; MICE AB Background: Cigarette smoke-induced chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory disorder of the lung. The development of effective therapies for COPD has been hampered by the lack of an animal model that mimics the human disease in a short timeframe. Objectives: We sought to create an early-onset mouse model of cigarette smoke-induced COPD that develops the hallmark features of the human condition in a short time-frame. We also sought to use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in patients with COPD. Methods: Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathologic features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated by using depletion and in vitro studies and MC protease 6-deficient mice. Results: After just 8 weeks of smoke exposure, wild-type mice had chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features of COPD were glucocorticoid resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart and increased susceptibility to respiratory tract infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced proinflammatory responses from cultured macrophages. Conclusion: A short-term mouse model of cigarette smoke-induced COPD was developed in which the characteristic features of the disease were induced more rapidly than in existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs. (J Allergy Clin Immunol 2013;131:752-62.) C1 [Beckett, Emma L.; Jarnicki, Andrew G.; Kim, Richard Y.; Hanish, Irwan; Hansbro, Nicole G.; Deane, Andrew; Keely, Simon; Horvat, Jay C.; Yang, Ming; Wark, Peter A.; Foster, Paul S.; Hansbro, Philip M.] Univ Newcastle, Prior Res Ctr Asthma & Resp Dis, Newcastle, NSW 2308, Australia. [Beckett, Emma L.; Jarnicki, Andrew G.; Kim, Richard Y.; Hanish, Irwan; Hansbro, Nicole G.; Deane, Andrew; Keely, Simon; Horvat, Jay C.; Yang, Ming; Wark, Peter A.; Foster, Paul S.; Hansbro, Philip M.] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2308, Australia. [Stevens, Richard L.; Soberman, Roy J.] Harvard Univ, Dept Med, Sch Med, Cambridge, MA 02138 USA. [Stevens, Richard L.; Hamadi, Sahar] Brigham & Womens Hosp, Boston, MA 02115 USA. [Oliver, Brian G.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Oliver, Brian G.] Univ Sydney, Woolcock Inst Med Res, Sydney, NSW 2006, Australia. [van Rooijen, Nico] Vrije Univ, Dept Mol Cell Biol, Med Ctr, Amsterdam, Netherlands. [Inman, Mark D.] St Josephs Healthcare, Firestone Inst Resp Hlth, Hamilton, ON, Canada. [Adachi, Roberto] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA. [Soberman, Roy J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wark, Peter A.] John Hunter Hosp, Dept Resp & Sleep Med, Newcastle, NSW, Australia. RP Hansbro, PM (reprint author), Univ Newcastle, Prior Res Ctr Asthma & Resp Dis, Newcastle, NSW 2308, Australia. EM Philip.Hansbro@newcastle.edu.au RI Foster, Paul/G-5057-2013; Oliver, Brian/E-7939-2010; OI Oliver, Brian/0000-0002-7122-9262; Kim, Richard/0000-0002-8709-5270; Wark, Peter/0000-0001-5676-6126; Hanish, Irwan/0000-0002-0478-7424; Beckett, Emma/0000-0002-8888-3789 FU National Health and Medical Research Council of Australia [510762, 569219, 1003565, 1003593, 1023131]; US National Institutes of Health [AI065858, AI059746]; Harvard Club of Australia Foundation; National Institutes of Health FX Supported by grants from the National Health and Medical Research Council of Australia (510762, 569219, 1003565, 1003593, and 1023131), the US National Institutes of Health (AI065858 and AI059746), and the Harvard Club of Australia Foundation.; Disclosure of potential conflict of interest: R. L. Stevens has been supported by one or more grants from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. NR 70 TC 60 Z9 62 U1 1 U2 30 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2013 VL 131 IS 3 BP 752 EP + DI 10.1016/j.jaci.2012.11.053 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA 098ZM UT WOS:000315587800017 PM 23380220 ER PT J AU Yu, YM Zhu, JH Huang, PS Wang, JH Pullen, N Springer, TA AF Yu, Yamei Zhu, Jianghai Huang, Po-Ssu Wang, Jia-huai Pullen, Nick Springer, Timothy A. TI Domain 1 of Mucosal Addressin Cell Adhesion Molecule Has an I1-set Fold and a Flexible Integrin-binding Loop SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-LEVEL EXPRESSION; STRUCTURAL SPECIALIZATIONS; CRYSTAL-STRUCTURE; I-DOMAIN; MADCAM-1; RECOGNITION; IMMUNOGLOBULIN; VCAM-1; ALPHA(4)BETA(7); FRAGMENT AB Mucosal addressin cell adhesion molecule (MAdCAM) binds integrin alpha(4)beta(7). Their interaction directs lymphocyte homing to mucosa-associated lymphoid tissues. The interaction between the two immunoglobulin superfamily (IgSF) domains of MAdCAM and integrin alpha(4)beta(7) is unusual in its ability to mediate either rolling adhesion or firm adhesion of lymphocytes on vascular surfaces. We determined four crystal structures of the IgSF domains of MAdCAM to test for unusual structural features that might correlate with this functional diversity. Higher resolution 1.7- and 1.4-angstrom structures of the IgSF domains of MAdCAM in a previously described crystal lattice revealed two alternative conformations of the integrin-binding loop, which were deformed by large lattice contacts. New crystal forms in the presence of two different Fabs to MAdCAM demonstrate a shift in IgSF domain topology from the I2- to I1-set, with a switch of integrin-binding loop from CC' to CD. The I1-set fold and CD loop appear biologically relevant. The different conformations seen in crystal structures suggest that the integrin-binding loop of MAdCAM is inherently flexible. This contrasts with rigidity of the corresponding loops in vascular cell adhesion molecule, intercellular adhesion molecule (ICAM)-1, ICAM-2, ICAM-3, and ICAM-5 and may reflect a specialization of MAdCAM to mediate both rolling and firm adhesion by binding to different alpha(4)beta(7) integrin conformations. C1 [Yu, Yamei; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02215 USA. [Yu, Yamei; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Huang, Po-Ssu] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Pullen, Nick] Pfizer Global Res & Dev, Cambridge, MA 02140 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, 3 Blackfan Circle, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Zhu, Jianghai/B-7339-2014 FU National Institutes of Health [HL103526] FX This work was supported, in whole or in part, by National Institutes of Health Grant HL103526. NR 46 TC 2 Z9 4 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 2013 VL 288 IS 9 BP 6284 EP 6294 DI 10.1074/jbc.M112.413153 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102CJ UT WOS:000315820700023 PM 23297416 ER PT J AU Zou, CB Chen, Y Smith, RM Snavely, C Li, J Coon, TA Chen, BB Zhao, YT Mallampalli, RK AF Zou, Chunbin Chen, Yan Smith, Rebecca M. Snavely, Courtney Li, Jin Coon, Tiffany A. Chen, Bill B. Zhao, Yutong Mallampalli, Rama K. TI SCFFbxw15 Mediates Histone Acetyltransferase Binding to Origin Recognition Complex (HBO1) Ubiquitin-Proteasomal Degradation to Regulate Cell Proliferation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; F-BOX; EPITHELIAL-CELLS; BETA-TRCP; PROTEIN; PHOSPHORYLATION; LIPOPOLYSACCHARIDE; ACTIVATION; LIGASES; ACETYLATION AB Histone acetyltransferase binding to origin recognition complex (HBO1) plays a crucial role in DNA replication licensing and cell proliferation, yet its molecular regulation in cells is relatively unknown. Here an uncharacterized protein, Fbxw15, directly interacts with HBO1, a labile protein (t(1/2) = similar to 3 h), to mediate its ubiquitination (Lys(338)) and degradation in the cytoplasm. Fbxw15-mediated HBO1 depletion required mitogen-activated protein kinase 1 (Mek1), which was sufficient to trigger HBO1 phosphorylation and degradation in cells. Mek1 ability to produce HBO1 degradation was blocked by Fbxw15 silencing. Lipopolysaccharide induced HBO1 degradation, an effect abrogated by Fbxw15 or Mek1 cellular depletion. Modulation of Fbxw15 levels was able to differentially regulate histone H3K14 acetylation and cellular proliferation by altering HBO1 levels. These studies authenticate Fbxw15 as a ubiquitin E3 ligase subunit that mediates endotoxin-induced HBO1 depletion in cells, thereby controlling cell replicative capacity. C1 [Zou, Chunbin; Chen, Yan; Smith, Rebecca M.; Snavely, Courtney; Li, Jin; Coon, Tiffany A.; Chen, Bill B.; Zhao, Yutong; Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Dept Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15260 USA. [Chen, Yan] Cent S Univ, Xiangya Hosp 2, Dept Internal Med, Div Resp Dis, Changsha 410011, Hunan, Peoples R China. RP Mallampalli, RK (reprint author), Dept Med, Div Pulm Allergy & Crit Care Med, 628 NW Montefiore,3459 5th Ave, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU National Institutes of Health [HL096376, HL097376, HL098174, HL116472, HL01916]; United States Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Biomedical Laboratory Research and Development; American Heart Association [12SDG12040330] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL096376, HL097376, and HL098174 (to R. K. M.), HL116472 (to B. B. C.), and HL01916 (to Y. Z.). This work was also supported in part by the United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, a Merit Review Award from the United States Department of Veterans Affairs, and American Heart Association Award 12SDG12040330 (to C. Z.). NR 46 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 2013 VL 288 IS 9 BP 6306 EP 6316 DI 10.1074/jbc.M112.426882 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102CJ UT WOS:000315820700025 PM 23319590 ER PT J AU Xu, AJ Springer, TA AF Xu, Amy J. Springer, Timothy A. TI Mechanisms by which von Willebrand Disease Mutations Destabilize the A2 Domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VONWILLEBRAND DISEASE; MULTIMERS; CLEAVAGE; ADHESION; UPDATE; IIA AB von Willebrand Factor (VWF) is an ultralong, concatameric, and adhesive glycoprotein. On short time scales, adhesiveness for platelets is activated by elongation of VWF by altered hydrodynamics at sites of hemostasis. Over longer time scales, the length of VWF is regulated by ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13), cleavage by which in the VWF A2 domain is dependent on elongational force. Patients with von Willebrand disease type 2A present with increased bleeding due to mutations within the VWF A2 domain that enhance cleavage. We tested using temperature and force the hypothesis that von Willebrand disease mutations disrupt A2 force sensing by destabilizing the folded state. Mutations R1597W, M1528V, and E1638K reduced A2 thermal stability by 10-18 degrees C. M1528V and E1638K showed a marked further decrease in stability upon calcium removal. In contrast, R1597W, which resides within the A2 calcium-binding loop, exhibited similar stability in the presence and absence of calcium. Using single molecule optical tweezers and R1597W, we measured the force dependence of unfolding and refolding kinetics. In the presence of calcium, the R1597W mutation slowed the rate of refolding but had no effect on unfolding. The three mutations highlight the calcium-binding loop (R1597W), the hydrophobic core around the vicinal disulfide (M1528V), and hydrogen bonds to the alpha 4-less loop (E1638K), as structural features critically important to the function of A2 as a force sensor in regulating thrombogenic activity in the vasculature. C1 [Springer, Timothy A.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, 3 Blackfan Circle, Boston, MA 02115 USA. EM springer@idi.harvard.edu FU National Institutes of Health [HL-48675]; Molecular Biophysics and General Medical Sciences Training Grants from NIGMS [T32 GM008313, GM007753] FX This work was supported by National Institutes of Health Grant HL-48675 (to T. A. S.) and Molecular Biophysics and General Medical Sciences Training Grants T32 GM008313 and GM007753 (from NIGMS; to A. J. X.). NR 25 TC 11 Z9 11 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 2013 VL 288 IS 9 BP 6317 EP 6324 DI 10.1074/jbc.M112.422618 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102CJ UT WOS:000315820700026 PM 23322777 ER PT J AU Wang, HY He, LF Ma, F Regan, MM Balk, SP Richardson, AL Yuan, X AF Wang, Hongyun He, Lingfeng Ma, Fen Regan, Meredith M. Balk, Steven P. Richardson, Andrea L. Yuan, Xin TI SOX9 Regulates Low Density Lipoprotein Receptor-related Protein 6 (LRP6) and T-cell Factor 4 (TCF4) Expression and Wnt/beta-catenin Activation in Breast Cancer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMARY STEM-CELLS; AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; BETA-CATENIN; CHONDROCYTE DIFFERENTIATION; INTESTINAL EPITHELIUM; CAMPOMELIC DYSPLASIA; TRANSCRIPTION FACTOR; GLAND DEVELOPMENT; WNT PROTEINS AB Gene expression profiling has identified breast cancer (BCa) subtypes, including an aggressive basal-like (BL) subtype. The molecular signals underlying the behavior observed in BL-BCa group are largely unknown, although recent results indicate a prevalent increase in Wnt/beta-catenin activity. Our immunohistochemistry study confirmed that SOX9, one of the BL-BCa signature genes, was expressed by most BL-BCa, and its expression correlated with indicators of poor prognosis. Importantly, BCa gene expression profiling strongly associated SOX9 with the expression of Wnt/beta-catenin pathway components, LRP6 and TCF4. In cancer cell lines, SOX9 silencing reduced cell proliferation and invasion, LRP6 and TCF4 transcription, and decreased Wnt/beta-catenin activation. SOX9 expression was also increased by Wnt, indicating that SOX9 is at the center of a positive feedback loop that enhances Wnt/beta-catenin signaling. Consistently, SOX9 overexpression in BCa cell lines and transgenic SOX9 expression in breast epithelium caused increased LRP6 and TCF4 expression and Wnt/beta-catenin activation. These results identify SOX9-mediated Wnt/beta-catenin activation as one of the molecular mechanisms underlying aberrant Wnt/beta-catenin activity in BCa, especially in the BL-BCa subgroup. C1 [Wang, Hongyun; He, Lingfeng; Ma, Fen; Balk, Steven P.; Yuan, Xin] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Richardson, Andrea L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. RP Richardson, AL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Smith 936A, Boston, MA 02215 USA. EM arichardson@partners.org; xyuan@bidmc.harvard.edu FU National Institutes of Health [R01 DK079962]; Dana-Farber/Harvard SPORE in Prostate Cancer Grant [P50 CA 090381]; Dana-Farber/Harvard SPORE in Breast Cancer Grant [CA089393]; Breast Cancer Research Foundation; Department of Defense [W81XWH-08-1-0160] FX This work was supported by National Institutes of Health Grant R01 DK079962 (to X. Y.); the Dana-Farber/Harvard SPORE in Prostate Cancer Grant P50 CA 090381 (to S. P. B.) and Dana-Farber/Harvard SPORE in Breast Cancer Grant CA089393 (to A. L. R.), the Breast Cancer Research Foundation (to A. L. R.), and Department of Defense Postdoctoral Award W81XWH-08-1-0160 (to H. W.). NR 60 TC 19 Z9 19 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 2013 VL 288 IS 9 BP 6478 EP 6487 DI 10.1074/jbc.M112.419184 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102CJ UT WOS:000315820700041 PM 23306204 ER PT J AU Hall, JA Dominy, JE Lee, Y Puigserver, P AF Hall, Jessica A. Dominy, John E. Lee, Yoonjin Puigserver, Pere TI The sirtuin family's role in aging and age-associated pathologies SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID FATTY-ACID OXIDATION; MITOCHONDRIAL PROTEIN HYPERACETYLATION; PANCREATIC BETA-CELLS; CALORIE RESTRICTION; LIFE-SPAN; GENE-EXPRESSION; HISTONE H3; IN-VIVO; SIRT3-MEDIATED DEACETYLATION; AXONAL DEGENERATION AB The 7 mammalian sirtuin proteins compose a protective cavalry of enzymes that can be invoked by cells to aid in the defense against a vast array of stressors. The pathologies associated with aging, such as metabolic syndrome, neurodegeneration, and cancer, are either caused by or exacerbated by a lifetime of chronic stress. As such, the activation of sirtuin proteins could provide a therapeutic approach to buffer against chronic stress and ameliorate age-related decline. Here we review experimental evidence both for and against this proposal, as well as the implications that isoform-specific sirtuin activation may have for healthy aging in humans. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Puigserver, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,CLSB 11144, Boston, MA 02215 USA. EM pere_puigserver@dfci.harvard.edu FU American Heart Association predoctoral fellowship; NIH National Research Service Award Kirschstein fellowship; Ewha Womans University; Dana-Farber Cancer Institute; American Diabetes Association; Department of Defense; NIH/NIDDK [RO1069966] FX J.A. Hall is supported by an American Heart Association predoctoral fellowship. J.E. Dominy is supported in part by an NIH National Research Service Award Kirschstein fellowship. Y. Lee is funded by a scholarship from Ewha Womans University. P. Puigserver has received support from the Dana-Farber Cancer Institute, American Diabetes Association, Department of Defense, and NIH/NIDDK (grant RO1069966). NR 124 TC 61 Z9 62 U1 0 U2 40 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2013 VL 123 IS 3 BP 973 EP 979 DI 10.1172/JCI64094 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 101BE UT WOS:000315749400008 PM 23454760 ER PT J AU Cai, CM Wang, HY He, HSHS Chen, S He, LF Ma, F Mucci, L Wang, QB Fiore, C Sowalsky, AG Loda, M Liu, XS Brown, M Balk, SP Yuan, X AF Cai, Changmeng Wang, Hongyun He, Housheng Hansen Chen, Sen He, Lingfeng Ma, Fen Mucci, Lorelei Wang, Qianben Fiore, Christopher Sowalsky, Adam G. Loda, Massimo Liu, X. Shirley Brown, Myles Balk, Steven P. Yuan, Xin TI ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TO-MESENCHYMAL TRANSITION; AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; TRANSCRIPTION FACTOR; CAMPOMELIC DYSPLASIA; UP-REGULATION; EXPRESSION; GROWTH; TUMOR; TMPRSS2-ERG AB Fusion of the androgen receptor-regulated (AR-regulated) TMPRSS2 gene with ERG in prostate cancer (PCa) causes androgen-stimulated overexpression of ERG, an ETS transcription factor, but critical downstream effectors of ERG-mediating PCa development remain to be established. Expression of the SOX9 transcription factor correlated with TMPRSS2:ERG fusion in 3 independent PCa cohorts, and ERG-dependent expression of SOX9 was confirmed by RNAi in the fusion-positive VCaP cell line. SOX9 has been shown to mediate ductal morphogenesis in fetal prostate and maintain stem/progenitor cell pools in multiple adult tissues, and has also been linked to PCa and other cancers. SOX9 overexpression resulted in neoplasia in murine prostate and stimulated tumor invasion, similarly to ERG. Moreover, SOX9 depletion in VCaP cells markedly impaired invasion and growth in vitro and in vivo, establishing SOX9 as a critical downstream effector of ERG. Finally, we found that ERG regulated SOX9 indirectly by opening a cryptic AR-regulated enhancer in the SOX9 gene. Together, these results demonstrate that ERG redirects AR to a set of genes including SOX9 that are not normally androgen stimulated, and identify SOX9 as a critical downstream effector of ERG in TMPRSS2:ERG fusion-positive PCa. C1 [Cai, Changmeng; Wang, Hongyun; Chen, Sen; He, Lingfeng; Ma, Fen; Sowalsky, Adam G.; Balk, Steven P.; Yuan, Xin] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Cai, Changmeng; Wang, Hongyun; Chen, Sen; He, Lingfeng; Ma, Fen; Sowalsky, Adam G.; Balk, Steven P.; Yuan, Xin] Harvard Univ, Sch Med, Boston, MA USA. [He, Housheng Hansen; Wang, Qianben; Fiore, Christopher; Loda, Massimo; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, Housheng Hansen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mucci, Lorelei] Dana Farber Canc Inst, Dept Epidemiol, Boston, MA 02115 USA. [Mucci, Lorelei] Dana Farber Canc Inst, Dept Nutr, Boston, MA 02115 USA. [Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM sbalk@bidmc.harvard.edu; xyuan@bidmc.harvard.edu RI Sowalsky, Adam/K-1485-2013; OI Sowalsky, Adam/0000-0003-2760-1853; Brown, Myles/0000-0002-8213-1658; Cai, Changmeng/0000-0002-8701-2586 FU NIH [R01 DK079962, K99 CA166507]; SPORE in Prostate Cancer [P50 CA090381]; Department of Defense [W81XWH-08-1-0160, W81XWH-09-1-0159, W81XWH-09-1-0435]; Prostate Cancer Foundation FX This work was supported by grants from the NIH (R01 DK079962 to X. Yuan, and K99 CA166507 to C. Cai); SPORE in Prostate Cancer P50 CA090381; postdoctoral awards from the Department of Defense (W81XWH-08-1-0160 to H. Wang, and W81XWH-09-1-0159 to C. Cai); Idea Development Award from the Department of Defense (W81XWH-09-1-0435 to S.P. Balk); and by a Challenge Award from the Prostate Cancer Foundation. NR 50 TC 44 Z9 44 U1 0 U2 42 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2013 VL 123 IS 3 BP 1109 EP 1122 DI 10.1172/JCI66666 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 101BE UT WOS:000315749400025 PM 23426182 ER PT J AU Leavenworth, JW Tang, XL Kim, HJ Wang, XY Cantor, H AF Leavenworth, Jianmei W. Tang, Xiaolei Kim, Hye-Jung Wang, Xiaoyang Cantor, Harvey TI Amelioration of arthritis through mobilization of peptide-specific CD8(+) regulatory T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RHEUMATOID-ARTHRITIS; ENDOPLASMIC-RETICULUM; SELF-TOLERANCE; ANIMAL-MODELS; IFN-GAMMA; IL-15; DISEASE; MICE AB Current therapies to treat autoimmune disease focus mainly on downstream targets of autoimmune responses, including effector cells and cytokines. A potentially more effective approach would entail targeting autoreactive T cells that initiate the disease cascade and break self tolerance. The murine MHC class Ib molecule Qa-1b (HLA-E in humans) exhibits limited polymorphisms and binds to 2 dominant self peptides: Hsp60(p216) and Qdm. We found that peptide-induced expansion of tetramer-binding CD8(+) Tregs that recognize Qa-1-Hsp60(p216) but not Qa-1-Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheumatoid arthritis. Perforin-dependent elimination of autoreactive follicular Th (T-FH) and Th17 cells by CD8(+) Tregs inhibited disease development. Infusion of in vitro-expanded CD8(+) Tregs increased the efficacy of methotrexate treatment and halted disease progression after clinical onset, suggesting an alternative approach to this first-line treatment. Moreover, infusion of small numbers of Qa-1-Hsp60(p216)-specific CD8(+) Tregs resulted in robust inhibition of autoimmune arthritis, confirming the inhibitory effects of Hsp60(p216) peptide immunization. These results suggest that strategies designed to expand Qa-1-restricted (HLA-E-restricted), peptide-specific CD8(+) Tregs represent a promising therapeutic approach to autoimmune disorders. C1 [Leavenworth, Jianmei W.; Tang, Xiaolei; Kim, Hye-Jung; Wang, Xiaoyang; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Leavenworth, Jianmei W.; Tang, Xiaolei; Kim, Hye-Jung; Wang, Xiaoyang; Cantor, Harvey] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA USA. [Wang, Xiaoyang] Univ Gothenburg, Dept Neurosci & Physiol, Sahlgrenska Acad, Perinatal Ctr, Gothenburg, Sweden. [Wang, Xiaoyang] Zhengzhou Univ, Affiliated Hosp 3, Dept Pediat, Zhengzhou, Peoples R China. RP Cantor, H (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Harvey_Cantor@dfci.harvard.edu FU NIH [AI 037562]; Swedish Research Council Award; VINNMER-Marie Curie international qualification (VINNOVA) [2011-03458]; National Research Service Award [T32 CA070083]; NovoNordisk A/G FX This work was supported in part by NIH research grant AI 037562, a collaborative research agreement with NovoNordisk A/G, and a gift from the LeRoy Schecter Research Foundation to H. Cantor; and a Swedish Research Council Award and VINNMER-Marie Curie international qualification (VINNOVA, 2011-03458) to X. Wang. J.W. Leavenworth is an National Research Service Award fellow (T32 CA070083); X. Tang is an NRSA fellow (T32 CA 009382); H.-J. Kim is a scholar of the Arthritis National Research Foundation. We thank C. Schellack Wenander for critical reading and insightful comments and A. Angel for manuscript and figure preparation. NR 45 TC 26 Z9 27 U1 0 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2013 VL 123 IS 3 BP 1382 EP 1389 DI 10.1172/JCI66938 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 101BE UT WOS:000315749400047 PM 23376792 ER PT J AU Dobs, AS Goldstein, BJ Aschner, P Horton, ES Umpierrez, GE Duran, L Hill, JS Chen, Y Golm, GT Langdon, RB Williams-Herman, DE Kaufman, KD Amatruda, JM Ferreira, JCA AF Dobs, Adrian S. Goldstein, Barry J. Aschner, Pablo Horton, Edward S. Umpierrez, Guillermo E. Duran, Lorraine Hill, Julie S. Chen, Yu Golm, Gregory T. Langdon, Ronald B. Williams-Herman, Debora E. Kaufman, Keith D. Amatruda, John M. Ferreira, Juan Camilo Arjona TI Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes SO JOURNAL OF DIABETES LA English DT Article DE dipeptidyl peptidase-4 inhibitor; glycemic control; incretins; sitagliptin ID DIPEPTIDYL PEPTIDASE-4 INHIBITOR; BETA-CELL FUNCTION; GLYCEMIC CONTROL; PLUS METFORMIN; PLASMA-GLUCOSE; PARALLEL-GROUP; DOUBLE-BLIND; PIOGLITAZONE; INCRETIN; GLP-1 AB Background: New therapeutic approaches are needed to improve glycemic control in patients with type 2 diabetes (T2D), a progressive disorder that often requires combination therapy. The present study assessed the efficacy and safety of sitagliptin as add-on therapy to metformin and rosiglitazone in patients with T2D. Methods: The present study was a randomized double-blind placebo-controlled parallel-group 54-week study conducted at 41 sites across North and South America, Europe, and Asia in 278 patients with HbA1c ranging from >= 7.5% to <= 11.0% despite ongoing combination therapy with metformin (>= 1500 mg/day) and rosiglitazone (>= 4 mg/day). Patients were randomized (2: 1) to receive sitagliptin 100 mg or placebo once daily. The main outcome measure was change from baseline in HbA1c at Week 18. Results: Mean baseline HbA1c was 8.8%. The mean placebo-adjusted change from baseline in HbA1c with sitagliptin treatment was) 0.7% (P < 0.001) at Week 18 and) -0.8% (P < 0.001) at Week 54. There were also significant (P < 0.001) reductions in 2-h post-meal glucose and fasting plasma glucose compared with placebo at Weeks 18 and 54. Significantly higher proportions of sitagliptin-than placebo-treated patients had HbA1c<7.0% at Weeks 18 (22% vs 9%; P = 0.003) and 54 (26% vs 14%; P = 0.015). Changes in body weight and the rates of adverse events overall, hypoglycemia, and gastrointestinal adverse events were similar in the sitagliptin and placebo groups during the 54-week study. Conclusions: In patients with T2D, the addition of sitagliptin for 54 weeks to ongoing therapy with metformin and rosiglitazone improved glycemic control and was generally well tolerated compared with placebo. C1 [Dobs, Adrian S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Goldstein, Barry J.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Goldstein, Barry J.; Duran, Lorraine; Hill, Julie S.; Chen, Yu; Golm, Gregory T.; Langdon, Ronald B.; Williams-Herman, Debora E.; Kaufman, Keith D.; Amatruda, John M.; Ferreira, Juan Camilo Arjona] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Umpierrez, Guillermo E.] Emory Univ, Sch Med, Atlanta, GA USA. [Aschner, Pablo] Javeriana Univ, Sch Med, Bogota, Colombia. [Aschner, Pablo] Colombian Diabet Assoc, Bogota, Colombia. RP Ferreira, JCA (reprint author), Merck Res Labs, 126 East Lincoln Ave,RY34-A232, Rahway, NJ 07065 USA. EM juan.arjona@merck.com FU Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA FX This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. The authors thank Sheila Erespe (Merck & Co.) for editorial assistance. NR 36 TC 23 Z9 27 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1753-0393 J9 J DIABETES JI J. Diabetes PD MAR PY 2013 VL 5 IS 1 BP 68 EP 79 DI 10.1111/j.1753-0407.2012.00223.x PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 087IG UT WOS:000314754200012 PM 22742523 ER PT J AU Chen, LM Birkmeyer, JD Saint, S Jha, AK AF Chen, Lena M. Birkmeyer, John D. Saint, Sanjay Jha, Ashish K. TI Hospitalist Staffing and Patient Satisfaction in the National Medicare Population SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID PRIMARY-CARE PHYSICIAN; QUALITY-OF-CARE; INPATIENT CARE; UNITED-STATES; HEART-FAILURE; IMPLEMENTATION; COMMUNICATION; PERFORMANCE; EXPERIENCE; IMPACT AB BACKGROUND Payers are increasingly holding hospitals accountable for patients' experiences with their care. This may conflict with another trend among US hospitalsgreater hospitalist careas hospitalists may have less familiarity with the history and preferences of their patients compared with primary-care physicians. OBJECTIVE Our objective was to better understand the relationship between hospitalist care and patients' experiences with their care. DESIGN This was a retrospective cohort study. SETTING The setting was 2843 US acute-care hospitals (bottom tertile or non-hospitalist hospitals: median of 0% of general-medicine patients cared for by hospitalists; middle tertile or mixed hospitals: median of 39.5%; top tertile or hospitalist hospitals: median of 76.5%). PATIENTS The patients were 132,814 hospitalized Medicare beneficiaries cared for by a general medicine physician in 2009. MEASUREMENTS The measurements were hospitalist use, based on Medicare claims data, and patient satisfaction, as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems survey. RESULTS Hospitalist hospitals had better performance on global measures of patient satisfaction than mixed or non-hospitalist hospitals (overall satisfaction: 65.6% vs 63.9% vs 63.9%, respectively, P value for difference < 0.001). Hospitalist hospitals performed better in 6 specific domains of care, with the largest difference in satisfaction with discharge compared with mixed or non-hospitalist hospitals (80.3% vs 79.1% vs 78.1%, P < 0.001). Hospitalist care was not associated with patient satisfaction in 2 domains of care: cleanliness of room and communication with physician. CONCLUSION For most measures of patient satisfaction, greater hospitalist care was associated with modestly better patient-centered care. Journal of Hospital Medicine 2013;8:126131. (c) 2012 Society of Hospital Medicine C1 [Chen, Lena M.; Saint, Sanjay] Univ Michigan, Div Gen Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Chen, Lena M.; Saint, Sanjay] VA Ann Arbor Healthcare Syst, Hosp Outcomes Program Excellence, Ann Arbor, MI USA. [Chen, Lena M.; Saint, Sanjay] VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, Ann Arbor, MI USA. [Chen, Lena M.; Birkmeyer, John D.] Univ Michigan, Ctr Healthcare Outcomes & Policy, Ann Arbor, MI 48109 USA. [Birkmeyer, John D.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Jha, Ashish K.] Harvard Univ, Sch Med, Boston, MA USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Chen, LM (reprint author), Univ Michigan, Div Gen Med, Dept Internal Med, North Campus Res Complex,2800 Plymouth Rd,Bldg 16, Ann Arbor, MI 48109 USA. EM lenac@umich.edu FU National Institutes of Health/National Institute on Aging (University of Michigan Claude D. Pepper Older Americans Independence Center) [AG024824]; National Institutes of Health/National Center for Research Resources (Michigan Institute for Clinical and Health Research) [UL1-RR024986]; Agency for Healthcare Research and Quality [K08HS020671] FX Dr. Chen's work is supported in part by the National Institutes of Health/National Institute on Aging (AG024824, University of Michigan Claude D. Pepper Older Americans Independence Center), and the National Institutes of Health/National Center for Research Resources (UL1-RR024986, Michigan Institute for Clinical and Health Research). Dr. Chen is also supported by a Career Development Grant Award (K08HS020671) from the Agency for Healthcare Research and Quality. NR 20 TC 8 Z9 8 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAR PY 2013 VL 8 IS 3 BP 126 EP 131 DI 10.1002/jhm.2001 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 100UZ UT WOS:000315731000003 PM 23288691 ER PT J AU Teekakirikul, P Kelly, MA Rehm, HL Lakdawala, NK Funke, BH AF Teekakirikul, Polakit Kelly, Melissa A. Rehm, Heidi L. Lakdawala, Neal K. Funke, Birgit H. TI Inherited Cardiomyopathies Molecular Genetics and Clinical Genetic Testing in the Postgenomic Era SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Review ID RIGHT-VENTRICULAR CARDIOMYOPATHY; FAMILIAL DILATED CARDIOMYOPATHY; CARDIAC TROPONIN-T; IDIOPATHIC RESTRICTIVE CARDIOMYOPATHY; SARCOMERE PROTEIN GENES; HYPERTROPHIC CARDIOMYOPATHY; HEART-FAILURE; ALPHA-TROPOMYOSIN; NON-COMPACTION; ECHOCARDIOGRAPHIC ANALYSIS AB Inherited cardiomyopathies include hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, Left ventricular noncompaction, and restrictive cardiomyopathy. These diseases have a substantial genetic component and predispose to sudden cardiac death, which provides a high incentive to identify and sequence disease genes in affected individuals to identify pathogenic variants. Clinical genetic testing, which is now widely available, can be a powerful tool for identifying presymptomatic individuals. However, locus and allelic heterogeneity are the rule, as are clinical variability and reduced penetrance of disease in carriers of pathogenic variants. These factors, combined with genetic and phenotypic overlap between different cardiomyopathies, have made clinical genetic testing a Lengthy and costly process. Next-generation sequencing technologies have removed many limitations such that comprehensive testing is now feasible, shortening diagnostic odysseys for clinically complex cases. Remaining challenges include the incomplete understanding of the spectrum of benign and pathogenic variants in the cardiomyopathy genes, which is a source of inconclusive results. This review provides an overview of inherited cardiomyopathies with a focus on their genetic etiology and diagnostic testing in the postgenomic era. (J Mol Diagn 2013, 15: 158-170; http://dx.doi.org/10.1016/j.jmoldx.2012.09.002) C1 [Teekakirikul, Polakit] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Teekakirikul, Polakit; Lakdawala, Neal K.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Teekakirikul, Polakit; Lakdawala, Neal K.; Funke, Birgit H.] Harvard Univ, Sch Med, Boston, MA USA. [Kelly, Melissa A.; Rehm, Heidi L.; Funke, Birgit H.] Partners HealthCare Ctr Personalized Genet Med, Lab Mol Med, Cambridge, MA 02139 USA. [Rehm, Heidi L.; Funke, Birgit H.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Funke, BH (reprint author), Partners HealthCare Ctr Personalized Genet Med, Lab Mol Med, 65 Landsdowne St, Cambridge, MA 02139 USA. EM bfunke@partners.org FU American Society for Clinical Pathology (ASCP); American Society for Investigative Pathology (ASIP) FX CME Accreditation Statement: This activity ("JMD 2013 CME Program in Molecular Diagnostics") has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Society for Clinical Pathology (ASCP) and the American Society for Investigative Pathology (ASIP). ASCP is accredited by the ACCME to provide continuing medical education for physicians. NR 99 TC 50 Z9 52 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAR PY 2013 VL 15 IS 2 BP 158 EP 170 DI 10.1016/j.jmoldx.2012.09.002 PG 13 WC Pathology SC Pathology GA 102JT UT WOS:000315841600003 PM 23274168 ER PT J AU Dapul, HR Park, J Zhang, J Lee, C DanEshmand, A Lok, J Ayata, C Gray, T Scalzo, A Qiu, JH Lo, EH Whalen, MJ AF Dapul, Heda R. Park, Juyeon Zhang, Jimmy Lee, Christopher DanEshmand, Ali Lok, Josephine Ayata, Cenk Gray, Tory Scalzo, Allison Qiu, Jianhua Lo, Eng H. Whalen, Michael J. TI Concussive Injury before or after Controlled Cortical Impact Exacerbates Histopathology and Functional Outcome in a Mixed Traumatic Brain Injury Model in Mice SO JOURNAL OF NEUROTRAUMA LA English DT Article DE brain injury; cognition; concussion; controlled cortical impact; mice; models ID DIFFUSE AXONAL INJURY; MICROGLIAL ACTIVATION; SEIZURE SUSCEPTIBILITY; CEREBRAL CONCUSSION; COGNITIVE DEFICITS; HEAD-INJURIES; CELL-DEATH; RATS; MOUSE; NEURODEGENERATION AB Traumatic brain injury (TBI) may involve diverse injury mechanisms (e. g., focal impact vs. diffuse impact loading). Putative therapies developed in TBI models featuring a single injury mechanism may fail in clinical trials if the model does not fully replicate multiple injury subtypes, which may occur concomitantly in a given patient. We report development and characterization of a mixed contusion/concussion TBI model in mice using controlled cortical impact (CCI; 0.6mm depth, 6 m/sec) and a closed head injury (CHI) model at one of two levels of injury (53 vs. 83 g weight drop from 66 in). Compared with CCI or CHI alone, sequential CCI-CHI produced additive effects on loss of consciousness (p < 0.001), acute cell death (p < 0.05), and 12-day lesion size (p < 0.05) but not brain edema or 48-h contusion volume. Additive effects of CHI and CCI on post-injury motor (p < 0.05) and cognitive (p < 0.005) impairment were observed with sequential CCI-CHI (83 g). The data suggest that concussive forces, which in isolation do not induce histopathological damage, exacerbate histopathology and functional outcome after cerebral contusion. Sequential CHI-CCI may model complex injury mechanisms that occur in some patients with TBI and may prove useful for testing putative therapies. C1 [Dapul, Heda R.; Park, Juyeon; Zhang, Jimmy; Lee, Christopher; DanEshmand, Ali; Lok, Josephine; Ayata, Cenk; Qiu, Jianhua; Lo, Eng H.; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Ctr, Charlestown, MA USA. [Dapul, Heda R.; Park, Juyeon; Zhang, Jimmy; Lee, Christopher; Lok, Josephine; Gray, Tory; Qiu, Jianhua; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Charlestown, MA USA. [DanEshmand, Ali; Ayata, Cenk; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Ayata, Cenk; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Scalzo, Allison] Penn State Univ, University Pk, PA 16802 USA. RP Whalen, MJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Charlestown, MA 02129 USA. EM mwhalen@partners.org FU [1R21NS075226]; [RO1NS047447]; [RO1NS064545] FX This work was supported by 1R21NS075226, RO1NS047447 and RO1NS064545 (MJW). NR 43 TC 8 Z9 10 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD MAR PY 2013 VL 30 IS 5 BP 382 EP 391 DI 10.1089/neu.2012.2536 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 103CI UT WOS:000315891600008 PM 23153355 ER PT J AU Josephson, L Rudin, M AF Josephson, Lee Rudin, Markus TI Barriers to Clinical Translation with Diagnostic Drugs SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE IND; NDA; imaging ID AGENTS AB Radioactive imaging agents, like diagnostic drugs generally, undergo a drug development process that parallels that of therapeutic agents, with similar development times but substantially lower development costs and substantially smaller postapproval markets. Although rapid advances in genetic and expression profiling are furthering the development of expensive pharmacotherapies targeted to small patient populations, the commercial development of imaging agents for small patient populations is blocked by the limited revenues available with current per-dose pricing and the relatively small numbers of imaging procedures that would be performed. A wide-ranging discussion on the best approaches to allow new diagnostic imaging agents to become part of the health-care system, and benefit the patient, is needed. C1 [Josephson, Lee] Massachusetts Gen Hosp, Dept Radiol, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA USA. [Josephson, Lee] Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Rudin, Markus] Univ Zurich, Inst Biomed Engn, Zurich, Switzerland. [Rudin, Markus] Swiss Fed Inst Technol, Zurich, Switzerland. [Rudin, Markus] Univ Zurich, Inst Pharmacol & Toxicol, Zurich, Switzerland. RP Josephson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149 13th St, Charlestown, MA 02129 USA. EM ljosephson@mgh.harvard.edu NR 11 TC 12 Z9 12 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR 1 PY 2013 VL 54 IS 3 BP 329 EP 332 DI 10.2967/jnumed.112.107615 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 099PA UT WOS:000315632500026 PM 23359658 ER PT J AU Johnson, KA Minoshima, S Bohnen, NI Donohoe, KJ Foster, NL Herscovitch, P Karlawish, JH Rowe, CC Carrillo, MC Hartley, DM Hedrick, S Pappas, V Thies, WH AF Johnson, Keith A. Minoshima, Satoshi Bohnen, Nicolaas I. Donohoe, Kevin J. Foster, Norman L. Herscovitch, Peter Karlawish, Jason H. Rowe, Christopher C. Carrillo, Maria C. Hartley, Dean M. Hedrick, Saima Pappas, Virginia Thies, William H. TI Appropriate Use Criteria for Amyloid PET: A Report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer's Association SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE guidelines; AUC; imaging; amyloid; MCI; Alzheimer's; PET; florbetapir; biomarker; beta-amyloid; dementia; radiopharmaceutical ID PITTSBURGH COMPOUND-B; POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; NATIONAL INSTITUTE; FDG-PET; A-BETA; NEUROPATHOLOGIC ASSESSMENT; DIFFERENTIAL-DIAGNOSIS; VASCULAR DEMENTIA; C-11-PIB PET AB Positron emission tomography (PET) of brain amyloid b is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. To provide guidance to dementia care practitioners, patients, and caregivers, the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be used appropriately. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. Although empirical evidence of impact on clinical outcomes is not yet available, a set of specific appropriate use criteria (AUC) were agreed on that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes. C1 [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Minoshima, Satoshi] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Bohnen, Nicolaas I.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Bohnen, Nicolaas I.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Bohnen, Nicolaas I.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Donohoe, Kevin J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Foster, Norman L.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Herscovitch, Peter] NIH, PET Dept, NIH Clin Ctr, Bethesda, MD 20892 USA. [Karlawish, Jason H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Rowe, Christopher C.] Austin Hlth, Dept Nucl Med, Heidelberg, Vic, Australia. [Rowe, Christopher C.] Austin Hlth, Ctr PET, Heidelberg, Vic, Australia. [Carrillo, Maria C.; Hartley, Dean M.; Thies, William H.] Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL 60601 USA. [Hedrick, Saima; Pappas, Virginia] Soc Nucl Med & Mol Imaging, Reston, VA USA. RP Carrillo, MC (reprint author), Alzheimers Assoc, Div Med & Sci Relat, Chicago, IL 60601 USA. EM maria.carrillo@alz.org NR 80 TC 68 Z9 70 U1 1 U2 35 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR 1 PY 2013 VL 54 IS 3 BP 476 EP 490 DI 10.2967/jnumed.113.120618 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 099PA UT WOS:000315632500045 PM 23359661 ER PT J AU Benkov, K Lu, Y Patel, A Rahhal, R Russell, G Teitelbaum, J AF Benkov, Keith Lu, Ying Patel, Ashish Rahhal, Riad Russell, Gary Teitelbaum, Jonathan CA NASPGHAN Comm Inflammatory Bowel TI Role of Thiopurine Metabolite Testing and Thiopurine Methyltransferase Determination in Pediatric IBD SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE azathioprine; Crohn disease; inflammatory bowel disease; 6-mercaptopurine; 6-methylmercaptopurine; 6-thioguanine nucleotides; thiopurine; thiopurine methyltransferase; ulcerative colitis ID INFLAMMATORY-BOWEL-DISEASE; 6-THIOGUANINE NUCLEOTIDE LEVELS; ADVERSE DRUG-REACTIONS; LONG-TERM TOXICITY; RED-BLOOD-CELLS; CROHNS-DISEASE; S-METHYLTRANSFERASE; AZATHIOPRINE THERAPY; 6-MERCAPTOPURINE THERAPY; COMBINATION THERAPY AB Thiopurines have been used in inflammatory bowel disease (IBD) for >30 years, and measurements of both thiopurine methyltransferase (TPMT) and thiopurine (TP) metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP), have been readily available. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Committee on Inflammatory Bowel Disease thought it appropriate to review the present indications for use of TPMT and TP metabolite testing. Substantial evidence demonstrates that TP therapy is useful for both Crohn disease and ulcerative colitis. Review of the existing data yielded the following recommendations. TPMT testing is recommended before initiation of TPs to identify individuals who are homozygote recessive or have extremely low TPMT activity, with the latter having more reliability than the former. Individuals who are homozygous recessive or have extremely low TPMT activity should avoid the use of TPs because of concerns for significant leukopenia. TMPT testing does not predict all cases of leukopenia and has no value to predict hypersensitivity adverse effects such as pancreatitis. Any potential value to reduce the risk of malignancy has not been studied. All individuals taking TPs should have routine monitoring with complete blood cell count and white blood cell count differential to evaluate for leukopenia regardless of TPMT testing results. Metabolite testing can be used to determine adherence with TP therapy. Metabolite testing can be used to guide dose increases or modifications in patients with active disease. Consideration would include either increasing the dose, changing therapy or for those with elevated transaminases or an elevated 6-MMP, using adjunctive allopurinol to help raise 6-thioguanine metabolites and suppress formation of 6-MMP. Routine and repetitive metabolite testing has little or no role in patients who are doing well and taking an acceptable dose of a TP. C1 [Benkov, Keith] Mt Sinai Sch Med, New York, NY 10029 USA. [Lu, Ying] Cohen Childrens Med Ctr New York, Lake Success, NY USA. [Patel, Ashish] Childrens Med Ctr Dallas, Dallas, TX USA. [Rahhal, Riad] Univ Iowa, Iowa City, IA USA. [Russell, Gary] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. [Teitelbaum, Jonathan] Drexel Univ, Sch Med, Philadelphia, PA 19104 USA. RP Benkov, K (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA. EM keith.benkov@mssm.edu NR 93 TC 10 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAR PY 2013 VL 56 IS 3 BP 333 EP 340 DI 10.1097/MPG.0b013e3182844705 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 097GG UT WOS:000315461400023 PM 23287804 ER PT J AU Tanpowpong, P Obuch, JC Jiang, HY McCarty, CE Katz, AJ Leffler, DA Kelly, CP Weir, DC Leichtner, AM Camargo, CA AF Tanpowpong, Pornthep Obuch, Joshua C. Jiang, Hongyu McCarty, Caitlin E. Katz, Aubrey J. Leffler, Daniel A. Kelly, Ciaran P. Weir, Dascha C. Leichtner, Alan M. Camargo, Carlos A., Jr. TI Multicenter Study on Season of Birth and Celiac Disease: Evidence for a New Theoretical Model of Pathogenesis SO JOURNAL OF PEDIATRICS LA English DT Article ID VITAMIN-D; PEDIATRIC-GASTROENTEROLOGY; INCREASED RISK; AUTOIMMUNITY; DIAGNOSIS; PREVALENCE; INFECTION; CHILDREN; GENDER; ASSOCIATION AB Objective To investigate whether season of birth is associated with celiac disease (CD). Study design We performed a medical record review of 1964 patients with biopsy-proven CD at 3 teaching hospitals (2 pediatric centers and 1 adult center) between 2000 and 2010. The first positive small intestinal biopsy result defined age of diagnosis. The observed proportions of births in each season (spring [March-May], summer [June-August], fall [September-November], and winter [December-February]) were compared with the expected proportions using binomial probability tests. Results The mean age at diagnosis was 9.8 +/- 5.0 years in the 2 pediatric centers and 43.6 +/- 15.8 years in the adult center. The cohort was predominately female (69%). Overall, more patients were born in spring (27%) than in any other season: summer (25%), fall (25%), and winter (23%). In patients diagnosed before age 15 years, the spring birth excess was present in boys (33%; P = .0005), but not in girls (26%; P = .43). The sex difference in season of birth was less striking in patients with CD diagnosed at age >= 15 years. Conclusion Season of birth is an environmental risk factor for CD, particularly in boys diagnosed before age 15 years. The results are consistent with a new theoretical model that integrates potential environmental factors (eg, gluten introduction, ultraviolet-B exposure, vitamin D status) and acute viral gastrointestinal infections in early childhood. (J Pediatr 2013;162:501-4). C1 [Tanpowpong, Pornthep; Katz, Aubrey J.] Massachusetts Gen Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Boston, MA 02114 USA. [Obuch, Joshua C.; Leffler, Daniel A.; Kelly, Ciaran P.] Beth Israel Deaconess Med Ctr, Celiac Ctr, Boston, MA 02215 USA. [Jiang, Hongyu; McCarty, Caitlin E.; Weir, Dascha C.; Leichtner, Alan M.] Boston Childrens Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 30 TC 7 Z9 8 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2013 VL 162 IS 3 BP 501 EP 504 DI 10.1016/j.jpeds.2012.08.056 PG 4 WC Pediatrics SC Pediatrics GA 101QS UT WOS:000315790100015 PM 23084709 ER PT J AU Timpano, KR Rasmussen, J Exner, C Rief, W Schmidt, NB Wilhelm, S AF Timpano, Kiara R. Rasmussen, Jessica Exner, Cornelia Rief, Winfried Schmidt, Norman B. Wilhelm, Sabine TI Hoarding and the multi-faceted construct of impulsivity: A cross-cultural investigation SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Hoarding; Impulsivity; Classification; Compulsivity ID OBSESSIVE-COMPULSIVE DISORDER; PSYCHOMETRIC PROPERTIES; COLLEGE-STUDENTS; LATENT STRUCTURE; DSM-V; INVENTORY; PERSONALITY; VERSION; MODEL; OCD AB The proposed hoarding disorder represents a serious psychiatric condition and considerable public health burden. Although tremendous strides have been made in understanding the phenomenology and treatment of this condition, many features regarding the etiology and nosology remain unclear. In particular, the association between impulsivity and hoarding, as well as the differential role of impulsivity versus compulsivity has yet to be fully considered. The current investigation sought to fill this gap in the literature by examining the relationship between hoarding and impulsivity across two independent, cross-cultural investigations. Two separate conceptualizations of the impulsivity construct were considered, including the Barratt Impulsivity Scale and the UPPS Impulsive Behavior Scale. Across Study 1 (US young adult sample; N = 372) and Study 2 (German young adult sample; N = 160) results revealed that hoarding was associated with greater rates of impulsivity, despite controlling for theoretically relevant covariates. More fined-grained analyses revealed a differential relationship with respect to the various facets of impulsivity, such that hoarding was most strongly linked with attentional and motor impulsivity, as well as urgency (i.e., impulsive behaviors in response to negative affect) and lack of perseverance. When considered simultaneously, both impulsivity and non-hoarding OCD symptoms explained unique variance in hoarding. The implications of impulsivity for hoarding are discussed from a classification perspective, as well as from a vulnerability standpoint. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Timpano, Kiara R.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Rasmussen, Jessica; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Exner, Cornelia] Univ Leipzig, Dept Psychol, Leipzig, Germany. [Rief, Winfried] Univ Marburg, Dept Psychol, D-35032 Marburg, Germany. [Schmidt, Norman B.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Timpano, KR (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd, Coral Gables, FL 33146 USA. EM kiaratimpano@gmail.com OI Exner, Cornelia/0000-0001-5904-6511; Timpano, Kiara/0000-0002-0665-8722 NR 51 TC 11 Z9 11 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAR PY 2013 VL 47 IS 3 BP 363 EP 370 DI 10.1016/j.jpsychires.2012.10.017 PG 8 WC Psychiatry SC Psychiatry GA 098HG UT WOS:000315539200011 PM 23168138 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Safe Travels! After Cancer Treatment SO JOURNAL OF TRAVEL MEDICINE LA English DT Editorial Material ID ORGAN TRANSPLANT RECIPIENTS; YELLOW-FEVER VACCINE; MORBIDITY C1 [Kotton, Camille Nelson] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kotton, Camille Nelson] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 16 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1195-1982 J9 J TRAVEL MED JI J. Travel Med. PD MAR-APR PY 2013 VL 20 IS 2 BP 69 EP 70 DI 10.1111/jtm.12014 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 104DX UT WOS:000315971600002 PM 23464711 ER PT J AU Sakhel, K Benson, CB Platt, LD Goldstein, SR Benacerraf, BR AF Sakhel, Khaled Benson, Carol B. Platt, Lawrence D. Goldstein, Steven R. Benacerraf, Beryl R. TI Begin With the Basics Role of 3-Dimensional Sonography as a First-line Imaging Technique in the Cost-effective Evaluation of Gynecologic Pelvic Disease SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID CONGENITAL UTERINE ANOMALIES; MULLERIAN DUCT ANOMALIES; MAGNETIC-RESONANCE; 3D SONOGRAPHY; ULTRASOUND; DIAGNOSIS; WOMEN; ACCURACY; HYSTEROSALPINGOGRAPHY; ULTRASONOGRAPHY C1 [Sakhel, Khaled] Eastern Virginia Med Sch, Dept Obstet & Gynecol, Norfolk, VA 23501 USA. [Benson, Carol B.; Benacerraf, Beryl R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Platt, Lawrence D.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Fetal Med & Womens Ultrasound, Los Angeles, CA 90095 USA. [Platt, Lawrence D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Goldstein, Steven R.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Benacerraf, Beryl R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benacerraf, Beryl R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Benacerraf, BR (reprint author), Harvard Univ, Sch Med, Dept Radiol, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 32 TC 9 Z9 9 U1 1 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2013 VL 32 IS 3 BP 381 EP 388 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 102HO UT WOS:000315835900001 PM 23443177 ER PT J AU Durfee, SM Benson, CB Adams, SR Ecker, J House, M Jennings, R Katz, D Pettigrew, C Wolfberg, A AF Durfee, Sara M. Benson, Carol B. Adams, Sonia R. Ecker, Jeffrey House, Michael Jennings, Russell Katz, Daniel Pettigrew, Courtenay Wolfberg, Adam TI Postnatal Outcome of Fetuses With the Prenatal Diagnosis of Gastroschisis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE gastroschisis; obstetric sonography; outcome ID ABDOMINAL-WALL DEFECTS; SONOGRAPHIC FINDINGS; ANTENATAL DIAGNOSIS; INTESTINAL DAMAGE; RISK-FACTORS; FETAL BOWEL; SURVEILLANCE; OMPHALOCELE; PREVALENCE; MANAGEMENT AB Objectives-The purpose of this study was to assess the postnatal outcome and complications that arise in infants with the prenatal diagnosis of gastroschisis. Methods-Prenatal sonograms with the diagnosis of gastroschisis were identified. Maternal age, indication for sonography, gestational age at diagnosis, other sonograpbic abnormalities, and postnatal outcome were recorded. Results-Ninety-eight fetuses at 14.3 to 36 weeks' gestation had the diagnosis of gastroschisis on sonography. In 14 cases (14%), other fetal anomalies were identified, including hydronephrosis, hydrocephalus, coarctation of the aorta, and a limb anomaly. Bowel dilatation developed in 72 of 84 cases (86%) followed prenatally with sonography, and bowel wall thickening developed in 40 of 73 cases (55%). On postnatal follow-up, 57 of 68 infants (84%) had postnatal complications, many with multisystem complications, including 6 deaths, 40 with bowel-related complications, 30 with infectious complications, and 32 with anomalies involving other systems (genitourinary, cardiac, and central nervous system). The postnatal outcome did not correlate with the presence of bowel dilatation or bowel wall thickening on prenatal sonography. Only 11 infants (16.2%) had a completely uncomplicated postsurgical course. Hospital stays in survivors (n = 92) ranged from 8 to 307 days (mean, 53 days). Conclusions-Although reported survival rates are good for gastroschisis, the postoperative hospital stay is often lengthy, and complications are very common, especially those related to the gastrointestinal tract. Associated anomalies were more common in our study than previously reported. C1 [Durfee, Sara M.; Benson, Carol B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Adams, Sonia R.; House, Michael; Pettigrew, Courtenay; Wolfberg, Adam] Tufts Med Ctr, Boston, MA USA. [Ecker, Jeffrey; Katz, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jennings, Russell] Childrens Hosp, Boston, MA 02115 USA. RP Durfee, SM (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM sdurfee@partners.org NR 37 TC 13 Z9 14 U1 0 U2 5 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2013 VL 32 IS 3 BP 407 EP 412 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 102HO UT WOS:000315835900004 PM 23443180 ER PT J AU Lin, NU AF Lin, Nancy U. TI Brain metastases in HER2-positive breast cancer SO LANCET ONCOLOGY LA English DT Editorial Material ID NERVOUS-SYSTEM METASTASES; TRASTUZUMAB; LAPATINIB; CAPECITABINE; TRIALS; WOMEN C1 Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, Boston, MA 02215 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Womens Canc, Boston, MA 02215 USA. EM nlin@partners.org NR 11 TC 3 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2013 VL 14 IS 3 BP 185 EP 186 DI 10.1016/S1470-2045(13)70046-9 PG 3 WC Oncology SC Oncology GA 103OV UT WOS:000315928800026 PM 23414590 ER PT J AU Pestalozzi, BC Holmes, E de Azambuja, E Metzger, O Hogge, L Scullion, M Lang, I Wardley, A Lichinitser, M Sanchez, RIL Muller, V Dodwell, D Gelber, RD Piccart-Gebhart, MJ Cameron, D AF Pestalozzi, Bernhard C. Holmes, Eileen de Azambuja, Evandro Metzger-Filho, Otto Hogge, Laurence Scullion, Matt Lang, Istvan Wardley, Andrew Lichinitser, Mikhail Lopez Sanchez, Roberto I. Mueller, Volkmar Dodwell, David Gelber, Richard D. Piccart-Gebhart, Martine J. Cameron, David TI CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01) SO LANCET ONCOLOGY LA English DT Article ID NERVOUS-SYSTEM METASTASES; BRAIN METASTASES; RISK; CHEMOTHERAPY; CARCINOMA; THERAPY AB Background Several randomised trials have confirmed the benefit of adjuvant trastuzumab for patients with HER2-positive early breast cancer. However, concern has been expressed that adjuvant trastuzumab might be associated with an increased frequency of CNS relapses. We assessed the frequency and course of CNS relapses, either as first event or at any time, using data from the HERA trial. Methods We estimated the cumulative incidence of first disease-free survival (DFS) events in the CNS versus other sites by competing risks analysis in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years (IQR 3.5-4.8). To obtain further information about CNS relapse at any time before death, we circulated a data collection form to investigators to obtain standardised information about CNS events that occurred in all patients who had died before July, 2009. We estimated the cumulative incidence of CNS relapse at any time with a competing risks analysis. Results Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2%) had a CNS relapse as first DFS event and 747 (22%) had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab (37 [2%] of 1703 patients) and the observation group (32 [2%] of 1698; p=0.55 [Gray's test]). 481 data collection forms were distributed, of which 413 (86%) were returned. The proportion of patients who had died and experienced a CNS relapse was numerically higher in the observation group (129 [57%] of 227) than in the group given trastuzumab for 1 year (88 [47%] of 186; p=0.06 [Gray's test]). Most CNS relapses were symptomatic (189 [87%] of 217). Conclusion Adjuvant trastuzumab does not increase the risk of CNS relapse in patients with HER2-positive early breast cancer. C1 [Pestalozzi, Bernhard C.] Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. [Holmes, Eileen] Frontier Sci Scotland, Kincraig, Scotland. [de Azambuja, Evandro; Hogge, Laurence] Inst Jules Bordet, B-1000 Brussels, Belgium. [de Azambuja, Evandro; Hogge, Laurence] Breast European Adjuvant Study Team, Brussels, Belgium. [Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Scullion, Matt] Roche Prod Dev Clin Oncol, Welwyn Garden City, Herts, England. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Wardley, Andrew] Christie Hosp, Dept Med Oncol, Manchester, Lancs, England. [Lichinitser, Mikhail] Blokhin Canc Res Ctr, Moscow, Russia. [Lopez Sanchez, Roberto I.] Isthmian Med Res Ctr SA, Panama City, Panama. [Mueller, Volkmar] Univ Klinikum Hamburg Eppendorf, Dept Gynecol, Hamburg, Germany. [Dodwell, David] St James Hosp, Inst Oncol, Leeds LS9 7TF, W Yorkshire, England. [Piccart-Gebhart, Martine J.] Univ Libre Brussels, Dept Med, Inst Jules Bordet, Brussels, Belgium. [Cameron, David] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Cameron, David] Western Gen Hosp, Dept Oncol, Edinburgh EH4 2XU, Midlothian, Scotland. RP Pestalozzi, BC (reprint author), Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. EM bernhard.pestalozzi@usz.ch RI Wardley, ANdrew/N-8135-2015 OI Wardley, ANdrew/0000-0002-9639-0888 FU Roche; GlaxoSmithKline FX EdA has received honoraria and a travel grant from Roche. MS is an employee of Roche Products. AW has received F Hoffmann-La Roche honoraria payments. VM has received speaker honoraria from Roche. MJP-G has received honoraria from Roche (40%. We then compared the IgG4-related RPF patients and the non-IgG4-related RPF patients in terms of both the presence of histopathologic features typical of IgG4-related disease and the simultaneous occurrence (or history) of other organ manifestations typical of IgG4-related disease. The IgG4-related RPF and non-IgG4-related RPF groups were also analyzed in terms of clinical, laboratory, and radiologic features and treatment review. We identified 13 cases of IgG4-related RPF (57% of the total cohort). The distinguishing features of IgG4-related RPF were histopathologic and extra-organ manifestations of IgG4-related disease. The IgG4-related RPF patients were statistically more likely than non-IgG4-related RPF patients to have retroperitoneal biopsies showing lymphoplasmacytic infiltrate (p = 0.006), storiform fibrosis (p = 0.006), or tissue eosinophilia (p = 0.0002). Demographics of the 2 groups, including a middle-aged, male predominance (mean age, 58 yr; 73% male), were similar. IgG4-related disease accounts for a substantial percentage of patients with "idiopathic" RPF. Histopathologic features such as storiform fibrosis, obliterative phlebitis, and tissue eosinophilia are critical to identifying this disease association. Extraretroperitoneal manifestations of IgG4-related disease are also often present among patients with IgG4-related RPF. Elevated IgG4/total IgG ratios in tissue biopsies are more useful than the number of IgG4+ plasma cells per high-power field in cases of RPF that are highly fibrotic. (Medicine 2013; 92: 82-91) C1 [Khosroshahi, Arezou; Carruthers, Mollie N.; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Shinagare, Shweta; Hasserjian, Robert P.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Shinagare, Shweta; Hasserjian, Robert P.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sainani, Nisha] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org FU Genentech; Roche; Genzyme (consultancy); Amgen (consultancy); Colorado Society of Pathologists; Elsevier; American Society for Clinical Pathology; United States and Canadian Academy of Pathology; Harvard Medical School FX Financial support and conflicts of interest: Dr. Stone reports financial support for work outside this study from Genentech (visiting lectureship and grant support to his institution for open label trial of rituximab in IgG4-related disease) and Roche (consultancy and grant support to his institution for multicenter clinical trial). Dr. Hasserjian reports financial support for work outside this study from Genzyme (consultancy) and Amgen (consultancy), as well as support from the Colorado Society of Pathologists, Elsevier, American Society for Clinical Pathology, United States and Canadian Academy of Pathology, and Harvard Medical School (for lectures, royalties, and/or travel expenses). NR 56 TC 46 Z9 53 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 2013 VL 92 IS 2 BP 82 EP 91 DI 10.1097/MD.0b013e318289610f PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 103VH UT WOS:000315947100003 PM 23429355 ER PT J AU Joffe, H Guthrie, KA Larson, J Cohen, LS Carpenter, JS LaCroix, AZ Freeman, EW AF Joffe, Hadine Guthrie, Katherine A. Larson, Joseph Cohen, Lee S. Carpenter, Janet S. LaCroix, Andrea Z. Freeman, Ellen W. TI Relapse of vasomotor symptoms after discontinuation of the selective serotonin reuptake inhibitor escitalopram: results from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health Research Network SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Hot flash; Vasomotor symptoms; Selective serotonin reuptake inhibitor; Escitalopram; Randomized trial; Recurrence; Relapse ID POSTMENOPAUSAL HORMONE-THERAPY; PLACEBO-CONTROLLED TRIAL; HOT FLASHES; WOMENS HEALTH; EXPERIENCE; EFFICACY AB Objective: Vasomotor symptoms (VMS) recur after discontinuation of hormonal therapy. Selective serotonin reuptake inhibitors (SSRIs) are used increasingly to treat VMS, but whether VMS recur after cessation of SSRI is unknown. We hypothesized that relapse of VMS to baseline levels after SSRI cessation would be common and predicted by menopausal and psychological characteristics. Methods: Recurrence of VMS (frequency, severity, and bother) was measured with daily diaries for 3 weeks after cessation of escitalopram, which was administered to perimenopausal/postmenopausal women with hot flashes and night sweats in an 8-week randomized, placebo-controlled trial. Blinding of staff and participants was maintained throughout. Relapse was defined as mean daily VMS frequency, severity, or bother 20% or less lower than pretreatment levels. Results: Of 76, 57, and 51 women included in the analysis for VMS frequency, severity, and bother, 34.2%, 38.6%, and 37.3%, respectively, had relapse of VMS frequency, severity, and bother. In adjusted models, VMS frequency relapse was predicted by higher levels of pretreatment insomnia symptoms (P = 0.02) and a weaker response to escitalopram (P = 0.03). Conclusions: Among women whose VMS improved with escitalopram, approximately one third relapsed swiftly after discontinuation of the medication. Those with pretreatment insomnia and those with a weaker response to escitalopram may be at greatest risk for VMS relapse after treatment discontinuation. Women should be educated about the likelihood of VMS symptom relapse when they discontinue SSRIs after receiving benefits from short-term treatment. C1 [Joffe, Hadine; Cohen, Lee S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Guthrie, Katherine A.; Larson, Joseph; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Freeman, Ellen W.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Womens Mental Hlth, 185 Cambridge St, Boston, MA 02114 USA. EM hjoffe@partners.org FU National Institute on Aging; Eunice Kennedy Shriver National Institute of Child Health and Development; National Center for Complementary and Alternative Medicine; Office of Research and Women's Health from the National Institute on Aging [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Indiana Clinical and Translational Sciences Institute; National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award [UL1 RR025761]; Forest Laboratories Inc.; Ortho-McNeil Janssen; Pfizer Inc.; Astra-Zeneca Pharmaceuticals; Bristol-Myers and Squib; Cephalon Inc.; GlaxoSmithKline; Sunovion Pharmaceuticals Inc.; Bionovo FX This study was supported by a cooperative agreement issued by the National Institute on Aging, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Center for Complementary and Alternative Medicine, and the Office of Research and Women's Health, and by grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700 from the National Institute on Aging. 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. Escitalopram and matching placebo pills were provided by Forest Research Institute.; Dr. Joffe serves on the board of Noven Pharmaceuticals Inc., is an unpaid consultant to Sunovion Pharmaceuticals, and has received a research grant from Cephalon Inc. Dr. Cohen consults for Noven Pharmaceutical and PamLab LLC and has received grants from Forest Laboratories Inc., Ortho-McNeil Janssen, Pfizer Inc., Astra-Zeneca Pharmaceuticals, Bristol-Myers and Squib, Cephalon Inc., GlaxoSmithKline, and Sunovion Pharmaceuticals Inc. Dr. LaCroix is a board member of the Center for Outcomes Research at the University of Massachusetts and the Amgen Scientific Methodology Advisory Committee for Profile. She is also a consultant for the Pfizer Mammographic Breast Density Advisory Meeting. Dr. Freeman has received research grants from Forest Laboratories Inc. and Bionovo. NR 13 TC 6 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR PY 2013 VL 20 IS 3 BP 261 EP 268 DI 10.1097/gme.0b013e31826d3108 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 099EN UT WOS:000315603200007 PM 23435022 ER PT J AU Kaneki, M Fukushima, Y Shinozaki, S Fukaya, M Habiro, M Shimizu, N Chang, K Yasuhara, S Martyn, JAJ AF Kaneki, Masao Fukushima, Yuji Shinozaki, Shohei Fukaya, Makiko Habiro, Mayu Shimizu, Nobuyuki Chang, Kyungho Yasuhara, Shingo Martyn, J. A. Jeevendra TI iNOS inhibitor, L-NIL, reverses bum-induced glycogen synthase kinase-3 beta activation in skeletal muscle of rats SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Akt/PKB ID NITRIC-OXIDE SYNTHASE; INDUCED INSULIN-RESISTANCE; BURN INJURY; TARGETED DISRUPTION; KINASE; CELLS; MICE; HYPERGLYCEMIA; EXPRESSION AB Objectives. Recent studies suggest that activation of glycogen synthase kinase (GSK)-3 beta may be involved in burn injury-induced metabolic derangements and protein breakdown in skeletal muscle. However, the mechanism for GSK-3 beta activation after burn injury is unknown. To investigate the role of inducible nitric oxide synthase (iNOS) in this scenario, a major mediator of inflammation, we examined the effects of a specific inhibitor for iNOS, L-NIL, on GSK-3 beta activity in skeletal muscle of burned rats. Materials/Methods. Full-thickness third degree burn injury comprising 40% of total body surface area was produced under anesthesia in male Sprague-Dawley rats (160-190g) by immersing the back of the trunk for 15s and the abdomen for Es in 80 degrees C water. Burned and sham-burned rats were treated with L-NIL (60mg/kg BW, b.i.d., IP) or phosphate-buffered saline for three days. GSK-3 beta activity in skeletal muscle was evaluated by immune complex kinase assay, and by phosphorylation status of GSK-3 beta and its endogenous substrate, glycogen synthase. Results. GSK-3 beta activity was increased in a time-dependent manner in skeletal muscle after burn injury, concomitant with the induction of iNOS expression. iNOS inhibitor, L-NIL, reverted the elevated GSK-3 beta activity in skeletal muscle of burned rats, although L-NIL did not alter GSK-3 beta activity in sham-burned rats. Conclusions. Our results clearly indicate that iNOS plays an important role in burn injury-induced GSK-3 beta activation in skeletal muscle. These findings suggest that iNOS may contribute to burn injury-induced metabolic derangements, in part, by activating GSK-3 beta. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kaneki, Masao; Fukushima, Yuji; Shinozaki, Shohei; Fukaya, Makiko; Habiro, Mayu; Shimizu, Nobuyuki; Chang, Kyungho; Yasuhara, Shingo; Martyn, J. A. Jeevendra] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Shriners Hosp Children, Boston, MA 02114 USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, 149 13th St, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu; jmartyn@etherdome.mgh.harvard.edu FU National Institutes of Health (NIH) [GM21700, GM31569, GM55082]; Microscopy and Image Analysis Core of Massachusetts General Hospital [P30NS045776]; Shriners Hospitals for Children; [DK58127] FX The present study was supported by grants of the National Institutes of Health (NIH) to J.A.J. Martyn (GM21700-Project 4, GM31569 and GM55082), M. Kaneki (DK58127), and the Microscopy and Image Analysis Core of Massachusetts General Hospital (P30NS045776), and Shriners Hospitals for Children (J.A.J. Martyn, M. Kaneki and S. Yasuhara). NR 22 TC 5 Z9 5 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 2013 VL 62 IS 3 BP 341 EP 346 DI 10.1016/j.metabol.2012.08.010 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 101BY UT WOS:000315751400004 PM 22995863 ER PT J AU Ciesienski, KL Yang, Y Ay, I Chonde, DB Loving, GS Rietz, TA Catana, C Caravan, P AF Ciesienski, Katie L. Yang, Yan Ay, Ilknur Chonde, Daniel B. Loving, Galen S. Rietz, Tyson A. Catana, Ciprian Caravan, Peter TI Fibrin-Targeted PET Probes for the Detection of Thrombi SO MOLECULAR PHARMACEUTICS LA English DT Article DE fibrin; copper; positron emission tomography; magnetic resonance imaging ID ANTI-D-DIMER; DEEP-VEIN THROMBOSIS; MR CONTRAST AGENT; PULMONARY EMBOLI; VENOUS THROMBI; MOLECULAR MRI; RECURRENT STROKE; FAB FRAGMENTS; AORTIC-ARCH; PHASE-II AB There is an ongoing effort to develop better methods for noninvasive detection and characterization of thrombi. Here we describe the synthesis and evaluation of three new fibrin-targeted positron emission tomography (PET) probes (FBP1, FBP2, FBP3). Three fibrin-specific peptides were conjugated as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-monoamides at the C- and N-termini and chelated with (CuCl2)-Cu-64. Probes were prepared with a specific activity ranging from 10 to 130 mu Ci/nmol. Both the peptides and the probes exhibited nanomolar dissociation constants (K-d) for the soluble fibrin fragment DD(E), although the Cu-DOTA derivatization resulted in a 2-3 fold loss in affinity relative to the parent peptide. Biodistribution and imaging studies were performed in a rat model of carotid artery thrombosis. For FBP1 and FBP2 at 120 min post injection, the vessel containing the thrombus showed the highest concentration of radioactivity after the excretory organs, that is, the liver and kidneys. This was confirmed ex vivo by autoradiography, which showed >4-fold activity in the thrombus-containing artery compared to the contralateral artery. FBP3 showed much lower thrombus uptake, and the difference was traced to greater metabolism of this probe. Hybrid MR-PET imaging with FBP1 or FBP2 confirmed that these probes were effective for the detection of an arterial thrombus in this rat model. A thrombus was visible on PET images as a region of high activity that corresponded to a region of arterial occlusion identified by simultaneous MR angiography. FBP1 and FBP2 represent promising new probes for the molecular imaging of thrombi. C1 [Caravan, Peter] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institutes of Health [R01HL109448, T32CA009502, P41RR14075] FX This work was supported in part by Awards R01HL109448, T32CA009502, and P41RR14075 from the National Institutes of Health. NR 67 TC 17 Z9 18 U1 1 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAR PY 2013 VL 10 IS 3 BP 1100 EP 1110 DI 10.1021/mp300610s PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 101GP UT WOS:000315763500031 PM 23327109 ER PT J AU Aster, JC DeAngelo, DJ AF Aster, Jon C. DeAngelo, Daniel J. TI Resistance revealed in acute lymphoblastic leukemia SO NATURE MEDICINE LA English DT Editorial Material ID MYELOID-LEUKEMIA; 5'-NUCLEOTIDASE; METABOLISM; MUTATIONS; RELAPSE AB The treatment of acute lymphoblastic leukemia (ALL) is one of the great success stories in oncology. However, patients who fail to achieve remission or relapse after chemotherapy continue to have a very poor prognosis, and the mechanisms underlying therapy failures are largely unknown. A new study suggests that gain-of-function mutations in NT5C2, a gene that encodes an enzyme that metabolizes chemotherapeutic drugs used against ALL, contribute to chemotherapy resistance (pages 368-371). C1 [Aster, Jon C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Aster, JC (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jaster@rics.bwh.harvard.edu; daniel_deangelo@dfci.harvard.edu NR 14 TC 1 Z9 1 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2013 VL 19 IS 3 BP 264 EP 265 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 105BN UT WOS:000316040700013 PM 23467232 ER PT J AU Unger, RH Berglund, ED Habener, JF Cherrington, AD AF Unger, Roger H. Berglund, Eric D. Habener, Joel F. Cherrington, Alan D. TI Dissecting the actions of widely used diabetes drugs SO NATURE MEDICINE LA English DT Editorial Material ID GLUCAGON AB The biguanides, first discovered as glucose-lowering agents isolated from French lilac (Galega officinalis) plants, are one of the most effective first-line drugs to treat type 2 diabetes. Despite the wide use of the biguanides metformin and phenformin, their mechanism of action has been unclear. In a recent study, Miller et al.(1) describe a new mechanism through which metformin antagonizes the hormone glucagon, thus reducing fasting glucose concentrations. The authors' findings add further support to the notion that glucagon is a major player in the pathogenesis of diabetes. We asked three experts to comment on these results and on how they might be applied to develop new, more efficacious therapies to target diabetes. C1 [Unger, Roger H.] Univ Texas SW Med Ctr Dallas, Touchstone Ctr Diabet Res, Dallas, TX 75390 USA. [Berglund, Eric D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, Dallas, TX 75390 USA. [Habener, Joel F.] Harvard Univ, Sch Med, Boston, MA USA. [Habener, Joel F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. [Habener, Joel F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cherrington, Alan D.] Vanderbilt Univ, Sch Med, Jacquelyn A Turner & Dr Dorothy J Turner Chair Di, Nashville, TN 37212 USA. RP Unger, RH (reprint author), Univ Texas SW Med Ctr Dallas, Touchstone Ctr Diabet Res, Dallas, TX 75390 USA. NR 10 TC 0 Z9 0 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2013 VL 19 IS 3 BP 272 EP 273 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 105BN UT WOS:000316040700017 PM 23467236 ER PT J AU Kiechl, S Wittmann, J Giaccari, A Knoflach, M Willeit, P Bozec, A Moschen, AR Muscogiuri, G Sorice, GP Kireva, T Summerer, M Wirtz, S Luther, J Mielenz, D Billmeier, U Egger, G Mayr, A Oberhollenzer, F Kronenberg, F Orthofer, M Penninger, JM Meigs, JB Bonora, E Tilg, H Willeit, J Schett, G AF Kiechl, Stefan Wittmann, Juergen Giaccari, Andrea Knoflach, Michael Willeit, Peter Bozec, Aline Moschen, Alexander R. Muscogiuri, Giovanna Sorice, Gian Pio Kireva, Trayana Summerer, Monika Wirtz, Stefan Luther, Julia Mielenz, Dirk Billmeier, Ulrike Egger, Georg Mayr, Agnes Oberhollenzer, Friedrich Kronenberg, Florian Orthofer, Michael Penninger, Josef M. Meigs, James B. Bonora, Enzo Tilg, Herbert Willeit, Johann Schett, Georg TI Blockade of receptor activator of nuclear factor-kappa B (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus SO NATURE MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE; PLASMID DNA; BONE LOSS; IKK-BETA; OSTEOPROTEGERIN; LIGAND; RISK; EXPRESSION; OBESITY; METABOLISM AB Hepatic insulin resistance is a driving force in the pathogenesis of type 2 diabetes mellitus (T2DM) and is tightly coupled with excessive storage of fat and the ensuing inflammation within the liver(1-3). There is compelling evidence that activation of the transcription factor nuclear factor-kappa B (NF-kappa B) and downstream inflammatory signaling pathways systemically and in the liver are key events in the etiology of hepatic insulin resistance and p-cell dysfunction, although the molecular mechanisms involved are incompletely understood(3-6). We here test the hypothesis that receptor activator of NE-kappa B ligand (RANKL), a prototypic activator of NF-kappa B, contributes to this process using both an epidemiological and experimental approach. In the prospective population-based Bruneck Study, a high serum concentration of soluble RANKL emerged as a significant (P < 0.001) and independent risk predictor of T2DM manifestation. In close agreement, systemic or hepatic blockage of RANKL signaling in genetic and nutritional mouse models of T2DM resulted in a marked improvement of hepatic insulin sensitivity and amelioration or even normalization of plasma glucose concentrations and glucose tolerance. Overall, this study provides evidence for a role of RANKL signaling in the pathogenesis of T2DM. If so, translation to the clinic may be feasible given current pharmacological strategies to lower RANKL activity to treat osteoporosis. C1 [Kiechl, Stefan; Knoflach, Michael; Willeit, Peter; Willeit, Johann] Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria. [Wittmann, Juergen; Mielenz, Dirk] Univ Erlangen Nurnberg, Dept Internal Med 3, Div Mol Immunol, D-91054 Erlangen, Germany. [Giaccari, Andrea; Muscogiuri, Giovanna; Sorice, Gian Pio] Univ Cattolica Sacro Cuore, Div Endocrinol & Metab Dis, Policlin A Gemelli, Rome, Italy. [Giaccari, Andrea] Fdn Don C Gnocchi, Milan, Italy. [Willeit, Peter] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Bozec, Aline; Kireva, Trayana; Luther, Julia; Schett, Georg] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. [Moschen, Alexander R.; Tilg, Herbert] Med Univ Innsbruck, Div Endocrinol Gastroenterol & Metab, Dept Med 1, A-6020 Innsbruck, Austria. [Summerer, Monika; Kronenberg, Florian] Med Univ Innsbruck, Div Genet Epidemiol Mol & Clin Pharmacol, Dept Med Genet, A-6020 Innsbruck, Austria. [Wirtz, Stefan; Billmeier, Ulrike] Univ Erlangen Nurnberg, Dept Internal Med 1, D-91054 Erlangen, Germany. [Egger, Georg; Oberhollenzer, Friedrich] Bruneck Hosp, Dept Internal Med, Brunico, Italy. [Mayr, Agnes] Bruneck Hosp, Dept Lab Med, Brunico, Italy. [Orthofer, Michael; Penninger, Josef M.] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1010 Vienna, Austria. [Meigs, James B.] Harvard Univ, Dept Internal Med, Boston, MA 02115 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Bonora, Enzo] Univ & Hosp Trust Verona, Div Endocrinol Diabet & Metab Dis, Verona, Italy. RP Kiechl, S (reprint author), Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria. EM stefan.kiechl@i-med.ac.at; georg.schett@uk-erlangen.de RI Penninger, Josef/I-6860-2013; Kronenberg, Florian/B-1736-2008; OI Penninger, Josef/0000-0002-8194-3777; Kronenberg, Florian/0000-0003-2229-1120; BONORA, Enzo/0000-0003-1074-5164 FU Deutsche Forschungsgemeinschaft [SPP1468-IMMUNOBONE]; Bundesministerium fur Bildung und Forschung (Bundesministerium fur Bildung und Forschung project ANCYLOSS); European Union; Innovative Medicines Initiative funded project BTCure; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; Genomics of Lipid-associated Disorders of the Austrian Genome Research Programme GEN-AU; 'Pustertaler Verein zur Pravention von Herz- und Hirngefasserkrankungen; Gesundheitsbetrieb Bruneck; Assessorat fur Gesundheitswesen, Familie und Soziales, Bolzand; Umberto Di Mario Prize by the Societa Italiana di Diabetologia; Fondazione Don Gnocchi; Universita Cattolica del Sacro Cuore (Fondi Ateneo Linea D.3.2 Sindrome Metabolica); Italian Ministry of Education, University and Research [PRIN 2010JS3PMZ_011]; Christian Doppler Research Society; Italian Ministry of Education, University and Research; University of Verona; European Research Council; Austrian Academy of Sciences; National Bank Foundation; Era of Hope/US Department of Defense FX This study was supported by the Deutsche Forschungsgemeinschaft (SPP1468-IMMUNOBONE to G.S.), the Bundesministerium fur Bildung und Forschung (Bundesministerium fur Bildung und Forschung project ANCYLOSS to G.S.), the European Union (Masterswitch to G.S.), the Innovative Medicines Initiative funded project BTCure (to G.S.), the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080140 to J.B.M.), the Genomics of Lipid-associated Disorders of the Austrian Genome Research Programme GEN-AU (to EK.), the 'Pustertaler Verein zur Pravention von Herz- und Hirngefasserkrankungen; the 'Gesundheitsbetrieb Bruneck' and the Assessorat fur Gesundheitswesen, Familie und Soziales, Bolzand. G.M. is recipient of the Umberto Di Mario Prize by the Societa Italiana di Diabetologia 2011. A.G. was supported by grants from Fondazione Don Gnocchi, Universita Cattolica del Sacro Cuore (Fondi Ateneo Linea D.3.2 Sindrome Metabolica) and the Italian Ministry of Education, University and Research (PRIN 2010JS3PMZ_011). A.M. and H.T. were supported by the Christian Doppler Research Society. E.B. is recipient of grants from the Italian Ministry of Education, University and Research and the University of Verona. J.M.P. holds an advanced European Research Council grant and is supported by the Austrian Academy of Sciences, a Grant by the National Bank Foundation and Era of Hope/US Department of Defense. We thank B. Enrich for technical support. NR 40 TC 65 Z9 69 U1 3 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2013 VL 19 IS 3 BP 358 EP 363 DI 10.1038/nm.3084 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 105BN UT WOS:000316040700030 PM 23396210 ER PT J AU Saylor, PJ AF Saylor, Philip J. TI PROSTATE CANCER The androgen receptor remains front and centre SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID ABIRATERONE; CHEMOTHERAPY; MITOXANTRONE; PREDNISONE; DOCETAXEL; SURVIVAL C1 Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM psaylor@partners.org NR 9 TC 13 Z9 13 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAR PY 2013 VL 10 IS 3 BP 126 EP 128 DI 10.1038/nrclinonc.2013.14 PG 3 WC Oncology SC Oncology GA 104FE UT WOS:000315976400002 PM 23381000 ER PT J AU Salsman, JM Butt, Z Pilkonis, PA Cyranowski, JM Zill, N Hendrie, HC Kupst, MJ Kelly, MAR Bode, RK Choi, SW Lai, JS Griffith, JW Stoney, CM Brouwers, P Knox, SS Cella, D AF Salsman, John M. Butt, Zeeshan Pilkonis, Paul A. Cyranowski, Jill M. Zill, Nicholas Hendrie, Hugh C. Kupst, Mary Jo Kelly, Morgen A. R. Bode, Rita K. Choi, Seung W. Lai, Jin-Shei Griffith, James W. Stoney, Catherine M. Brouwers, Pim Knox, Sarah S. Cella, David TI Emotion assessment using the NIH Toolbox SO NEUROLOGY LA English DT Article ID POSITIVE EMOTIONS; PSYCHOLOGICAL STRESS; DEPRESSIVE SYMPTOMS; HEALTH; LIFE; WELL; LONELINESS; RECOVERY; PURPOSE; RISK AB One of the goals of the NIH Toolbox for Assessment of Neurological and Behavioral Function was to identify or develop brief measures of emotion for use in prospective epidemiologic and clinical research. Emotional health has significant links to physical health and exerts a powerful effect on perceptions of life quality. Based on an extensive literature reviewand expert input, the Emotion team identified 4 central subdomains: Negative Affect, Psychological Well-Being, Stress and Self-Efficacy, and Social Relationships. A subsequent psychometric review identified several existing self-report and proxy measures of these subdomains with measurement characteristics that met the NIH Toolbox criteria. In cases where adequate measures did not exist, robust item banks were developed to assess concepts of interest. A population-weighted sample was recruited by an online survey panel to provide initial item calibration andmeasure validation data. Participants aged 8 to 85 years completed self-report measures whereas parents/guardians responded for children aged 3 to 12 years. Data were analyzed using a combination of classic test theory and item response theory methods, yielding efficient measures of emotional health concepts. An overview of the development of the NIH Toolbox Emotion battery is presented along with preliminary results. Norming activities led to further refinement of the battery, thus enhancing the robustness of emotional health measurement for researchers using the NIH Toolbox. Neurology (R) 2013; 80 (Suppl3):S76-S86 C1 [Salsman, John M.; Butt, Zeeshan; Choi, Seung W.; Lai, Jin-Shei; Griffith, James W.; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Bode, Rita K.] Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. [Salsman, John M.; Lai, Jin-Shei; Cella, David] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Butt, Zeeshan] Northwestern Univ, Comprehens Transplant Ctr, Chicago, IL 60611 USA. [Salsman, John M.; Butt, Zeeshan; Lai, Jin-Shei; Griffith, James W.; Cella, David] Northwestern Univ, Ctr Patient Centered Outcomes, Chicago, IL 60611 USA. [Pilkonis, Paul A.; Cyranowski, Jill M.; Kelly, Morgen A. R.] Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA USA. [Zill, Nicholas] Westat Corp, Rockville, MD USA. [Hendrie, Hugh C.] Indiana Univ Sch Med, Ctr Aging Res, Indianapolis, IN USA. [Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Kelly, Morgen A. R.] Family Serv Western Pennsylvania, Pittsburgh, PA USA. [Kelly, Morgen A. R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Stoney, Catherine M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Brouwers, Pim] NIH, Div AIDS Res, Bethesda, MD 20892 USA. [Knox, Sarah S.] W Virginia Univ, Sch Med, Dept Community Med, Morgantown, WV 26506 USA. RP Salsman, JM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. EM j-salsman@northwestern.edu RI Griffith, James/O-2551-2016 OI Griffith, James/0000-0002-4840-8692 FU Office of Behavioral and Social Sciences Research, NIH [HHS-N-260-2006-00007-C]; Blueprint for Neuroscience Research; NIH [HHSN265200423601C, U01 AR052177-05, KL2RR0254740, HD067440, DK091786, DK062467-10, DK06246708S1, AR052155, AT006453, MH056888, MH066302, MH090333, HL076852, AR52155, MH37896, MH085874, MH083647, AG012546, AR052186, MH086637, U01 DK082342]; GlaxoSmithKline; American Cancer SocietyIllinois Division [PSB-08-15]; National Cancer Institute [5K07CA158008-01A1]; Boehringer Ingelheim; Pfizer; Patient-Centered Outcomes Research Institute (PCORI); Daiichi Sankyo, Inc.; Frankel Foundation; Pittsburgh Foundation; National Council for Adoption; Brookings Institution; Marriage and Religion Research Institute; NorthShore University HealthSystem; Cleveland Clinic Foundation/Teva Neurosciences, Inc.; Ironwood Pharmaceuticals, Inc.; Forest Laboratories, Inc.; Department of Defense (DOD)-United States Army; FWO FX This study is funded in whole or in part with Federal funds from the Blueprint for Neuroscience Research and the Office of Behavioral and Social Sciences Research, NIH, under contract no. HHS-N-260-2006-00007-C.; J. Salsman served as an independent contractor for the RTOG (Study no. 0841) and has received research support from the NIH (Contract no. HHSN265200423601C), GlaxoSmithKline, the American Cancer SocietyIllinois Division (PSB-08-15), and the NIH (U01 AR052177-05). He currently receives research support from the National Cancer Institute (5K07CA158008-01A1). Z. Butt served as a consultant for Johnson & Johnson and the American Society of Transplant Surgeons. He received support from Boehringer Ingelheim, Pfizer, the Patient-Centered Outcomes Research Institute (PCORI), and NIH grant KL2RR0254740. He currently receives research support from Daiichi Sankyo, Inc., the Frankel Foundation, and NIH grants HD067440, DK091786, DK062467-10, and DK06246708S1. P. Pilkonis served as a consultant for Lundbeck Pharmaceuticals. He currently receives support from NIH grants AR052155, AT006453, MH056888, MH066302, and MH090333. J. Cyranowski has received research funding from the Pittsburgh Foundation and from NIH grants HL076852, AR52155, and MH37896; she currently receives research support from NIH grants MH085874, MH083647, AG012546, AR052186, and MH086637. N. Zill received research support from the National Council for Adoption, the Brookings Institution, and the Marriage and Religion Research Institute. He served as a reviewer for an NIH SBIR Review Panel. He holds a TIAA-CREF Retirement Annuity Contract that invests in US Treasury Bonds and an International Stock Index Fund. He received consulting income and income from selling stock and exercising stock options from Westat, an employee-owned S Corporation. He holds an IRA and brokerage account with Vanguard that includes holdings in the Vanguard Health Care, Precious Metals and Mining, High-Yield Corporate Bond, High-Yield Tax Exempt Bond, and Long-Term Corporate Bond mutual funds, as well as the Vanguard Consumer Discretionary, Consumer Staples, FTSE International Small Cap, and Corporate Long-Term Bond Exchange Traded Funds. He has holdings in a number of closed-ended mutual funds, including the Aberdeen Asia Pacific Income Fund, Templeton Global High Income Fund, Templeton Dragon Fund, Alliance-Bernstein Global High Income Fund, Alliance-Bernstein Corporate Income Fund, Blackrock Income Opportunity Trust, Putnam Master Intermediate Income Trust, Nuveen Floating Rate Income Opportunity Fund, India Fund, Morgan Stanley India Investment Fund, Latin American Discovery Fund, Aberdeen Latin American Equity Fund, Singapore Fund, and Turkish Investment Fund. He has stock holdings in AT& T, Boardwalk Pipeline Partners, Banco de Columbia, Consolidated Edison, Exxon, Frontier Communications, GlaxoSmithKline, Honeywell, Huntington Ingalls Industries, IBM, Intel, 3M, MeadWestvaco, Newell Rubbermaid, Northrop Grumman, Occidental Petroleum, SCANA, Sherwin-Williams, Siemens, Southern, Verizon, Johnson Controls, American Superconductor, Ocean Power Technology, and Maxwell Technology. Dr. Zill's wife, Karen, prepared discussion guides for the Independent Lens program on PBS. She holds a TIAA Retirement Annuity Contract that invests in US Treasury Bonds. H. Hendrie currently receives research funding from NIH/NIA grant R01AG009956, R24MH080827, 5R01AG026096-05, UF20303/U01AG022376, R01AG031222, R01AG019181, and R01AG029884. M. Kupst reports no disclosures. M. Kelly has been employed by the University of Pittsburgh School of Medicine and Family Services of Western Pennsylvania. Dr.; Kelly is the coprincipal investigator on a study sponsored by Ortho McNeil Janssen for which Family Services of Western Pennsylvania receives remuneration. Dr. Kelly does not receive direct remuneration for her role in that study. R. Bode reports no disclosures. S. Choi has received research support from Boehringer-Ingelheim, Novartis, and the NIH. J.-S. Lai has received research support from the NIH, Agency for Healthcare Research and Quality, and Pfizer, Inc. J. Griffith has received financial support from NorthShore University HealthSystem, the Cleveland Clinic Foundation/Teva Neurosciences, Inc., Ironwood Pharmaceuticals, Inc., and Forest Laboratories, Inc., the NIH, the Department of Defense (DOD)-United States Army, and the FWO, Belgium. In addition to NIH Toolbox funding, he receives funding from the NIH for other research (grant U01 DK082342). He has also been a paid consultant to Dr. Kathryn Grant of DePaul University, and maintains a clinical psychology practice for which he bills for his services. C. Stoney reports no disclosures. P. Brouwers and S. Knox report no disclosures. D. Cella serves on the editorial board of the Journal of Supportive Oncology, has received travel support from Pfizer, honoraria from Virginia Commonwealth University and Moffit Cancer Center for speaking engagements, and research support from Boehringer-Ingelheim, Novartis, and the NIH. He also receives royalties from Up to Date. Go to Neurology. org for full disclosures. NR 33 TC 10 Z9 10 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 2013 VL 80 SU 3 BP S76 EP S86 DI 10.1212/WNL.0b013e3182872e11 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 104LS UT WOS:000315995100014 PM 23479549 ER PT J AU Yanamadala, V Walcott, BP Nahed, BV Barker, FG AF Yanamadala, Vijay Walcott, Brian P. Nahed, Brian V. Barker, Fred G., II TI Retrograde Third Ventriculocisternostomy From the Posterior Fossa SO NEUROSURGERY LA English DT Article DE Cerebellopontine; Cerebrospinal fluid; Hydrocephalus; Posterior fossa; Third ventriculostomy ID GIANT ACOUSTIC NEUROMAS; PERSISTENT HYDROCEPHALUS; PEDIATRIC-PATIENTS; TUMOR SURGERY; VENTRICULOSTOMY; CHILDREN; MANAGEMENT; CSF; REMOVAL; SHUNT AB BACKGROUND: Postoperative hydrocephalus is common in patients after resection of a posterior fossa tumor, with as many as 25% of patients requiring permanent cerebrospinal fluid diversion in the form of ventricular shunting or ventriculocisternostomy in some series. Prophylactic ventriculocisternostomy has been described with success in this patient population to prevent postoperative hydrocephalus. OBJECTIVE: To define the technique of microsurgical retrograde third ventriculostomy from the posterior fossa. METHODS: The operative technique is described and a single patient with 4-year follow-up is reported. RESULTS: We describe the case of a 32-year-old woman who presented with a large cerebellopontine angle epidermoid tumor. She underwent a simultaneous lesion resection and third ventriculocisternostomy by accessing the interpeduncular cistern via a suboccipital posterior fossa approach and then making an incision through the tuber cinereum to access the third ventricle under direct vision. CONCLUSION: Retrograde third ventriculostomy may be useful in the surgical treatment of patients already undergoing operations for large posterior fossa lesions who have a high likelihood of requiring permanent cerebrospinal fluid diversion and in whom exposure of the interpeduncular cistern is available. C1 [Yanamadala, Vijay; Walcott, Brian P.; Nahed, Brian V.; Barker, Fred G., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Dept Surg Neurosurg, Boston, MA 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 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 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 2013 VL 72 SU S BP 9 EP 13 AR ons9 DI 10.1227/NEU.0b013e3182744b67 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 103UK UT WOS:000315944800006 PM 23037821 ER PT J AU Beverly, EA Caballero, AE Fitzgerald, S Ganda, OP Weinger, K AF Beverly, Elizabeth A. Caballero, A. Enrique Fitzgerald, Shane Ganda, Om P. Weinger, Katie TI Older Adults with Diabetes Benefit from Diabetes Education Similarly to Younger and Middle-Aged Adults SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Beverly, Elizabeth A.; Caballero, A. Enrique; Ganda, Om P.; Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E37 EP E37 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300104 ER PT J AU Boucher, JE Berry, D Boyajian, R Mcdermott, K Roper, K Underhill, M Walsh, M AF Boucher, Jean E. Berry, Donna Boyajian, Richard Mcdermott, Kathleen Roper, Kristin Underhill, Meghan Walsh, Michele TI Description of Baseline Data from a Nurse-led Home Based Activity Intervention for Patients with Cancer Related Fatigue SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Boucher, Jean E.] Univ Massachusetts Worcester, Worcester, MA USA. [Berry, Donna; Boyajian, Richard; Mcdermott, Kathleen; Roper, Kristin; Walsh, Michele] Dana Farber Canc Inst, Boston, MA USA. [Underhill, Meghan] U Mass Boston, Dana Farber Canc Inst, 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E50 EP E51 PG 2 WC Nursing SC Nursing GA 103WX UT WOS:000315951300141 ER PT J AU Boucher, JE Berry, D Boyajian, R McDermott, K Roper, K Underhill, M Walsh, M Yeh, YT AF Boucher, Jean E. Berry, Donna Boyajian, Rochard McDermott, Kathleen Roper, Kristin Underhill, Meghan Walsh, Michelle Yeh, Yating TI Description and Correlations of Initial Patient Reported Cancer Related Fatigue and Activity Diary Data; Outcomes from a Summer Student Internship SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Boucher, Jean E.; Berry, Donna; Boyajian, Rochard; McDermott, Kathleen; Roper, Kristin; Walsh, Michelle; Yeh, Yating] Dana Farber Canc Inst, Boston, MA USA. [Underhill, Meghan] U Mass Boston, Dana Farber Canc Inst, Boston, MA 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E50 EP E50 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300140 ER PT J AU Corless, IB Brion, J Chen, WT Cuca, Y Rose, CD Eller, LS Hickey, D Holzemer, WL Hoyt, A Huang, E Iipinge, S Johnson, MO Kemppainen, J Kirksey, K Lindgren, T Maryland, M Nicholas, PK Nokes, KM Phillips, JC Portillo, C Reid, P Rivero-Mendez, M Sefcik, E Sullivan, K Tyer-Viola, LA Voss, J Wantland, D Webel, A AF Corless, Inge B. Brion, John Chen, Wei-Ti Cuca, Yvette Rose, Carol Dawson Eller, Lucille S. Hickey, Dorothy Holzemer, William L. Hoyt, Alex Huang, Emily Iipinge, Scholastika Johnson, Mallory O. Kemppainen, Jeanne Kirksey, Kenn Lindgren, Teri Maryland, Mary Nicholas, Patrice K. Nokes, Kathleen M. Phillips, J. Craig Portillo, Carmen Reid, Paula Rivero-Mendez, Marta Sefcik, Elizabeth Sullivan, Kathleen Tyer-Viola, Lynda A. Voss, Joachim Wantland, Dean Webel, Allison TI Why Do Women Stop Taking Antiretroviral Medications? SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Corless, Inge B.; Hoyt, Alex; Nicholas, Patrice K.; Tyer-Viola, Lynda A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Brion, John] Duke Univ, Durham, NC 27706 USA. [Chen, Wei-Ti] Yale Univ, Coll Nursing, New Haven, CT 06520 USA. [Cuca, Yvette; Huang, Emily; Portillo, Carmen] UCSF, San Francisco, CA USA. [Rose, Carol Dawson] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eller, Lucille S.; Holzemer, William L.] Rutgers State Univ, Piscataway, NJ 08855 USA. [Hickey, Dorothy] NYU, Coll Nursing, New York, NY 10003 USA. [Iipinge, Scholastika] Univ Namibia, Windhoek, Namibia. [Kemppainen, Jeanne; Reid, Paula] Univ N Carolina Wilmington, Wilmington, NC USA. [Kirksey, Kenn] Lyndon B Johnson Hosp, Houston, TX USA. [Maryland, Mary] Chicago State Univ, Chicago, IL USA. [Phillips, J. Craig] Univ Ottawa, Ottawa, ON K1N 6N5, Canada. [Rivero-Mendez, Marta] Univ Puerto Rico, San Juan, PR 00936 USA. [Sefcik, Elizabeth] Texas A&M Univ Corpus Christi, Corpus Christi, TX USA. [Sullivan, Kathleen] Univ Hawaii, Manoa, HI USA. [Voss, Joachim] Univ Washington, Seattle, WA 98195 USA. [Webel, Allison] Case Western Reserve Univ, Cleveland, OH 44106 USA. RI Brion, John/B-3623-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E38 EP E38 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300108 ER PT J AU Cronin, JA AF Cronin, Julie A. TI Family Member's Perceptions of Most Helpful Interventions during End-of-Life Care of a Loved One SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Cronin, Julie A.] 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E55 EP E55 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300152 ER PT J AU D'Alonzo, KT DeMarco, RF DeSanto-Madeya, S Horowitz, JA Moriarty, HJ Shepard, M AF D'Alonzo, Karen T. DeMarco, Rosanna F. DeSanto-Madeya, Susan Horowitz, June Andrews Moriarty, Helene J. Shepard, Margaret TI Effective use of Critique and Dialog at Academic Conferences- Building a Community of Scholars SO NURSING RESEARCH LA English DT Meeting Abstract C1 [D'Alonzo, Karen T.] Rutgers State Univ, Piscataway, NJ 08855 USA. [DeMarco, Rosanna F.; Horowitz, June Andrews] Boston Coll, Chestnut Hill, MA 02167 USA. [DeSanto-Madeya, Susan] Univ Massachusetts Boston, Boston, MA USA. [Moriarty, Helene J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Shepard, Margaret] UMDNJ, Newark, NJ 07107 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E7 EP E8 PG 2 WC Nursing SC Nursing GA 103WX UT WOS:000315951300020 ER PT J AU Ditomassi, M Erickson, JI AF Ditomassi, Marianne Erickson, Jeanette Ives TI Innovation Units: Effective Testing Grounds For Change SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Ditomassi, Marianne; Erickson, Jeanette Ives] 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E4 EP E4 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300011 ER PT J AU Flanagan, J Habin, K Pos, K Winters, L AF Flanagan, Jane Habin, Karleen Pos, Kathryn Winters, Loren TI Women's Experiences of Transitioning to Endocrine-based Oral Therapy SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Flanagan, Jane] Boston Coll, Chestnut Hill, MA 02167 USA. [Habin, Karleen] 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E33 EP E34 PG 2 WC Nursing SC Nursing GA 103WX UT WOS:000315951300095 ER PT J AU Horowitz, JA DuBois, N Hayes, M Moriarty, HJ Zirkle, D AF Horowitz, June Andrews DuBois, Nancy Hayes, Margaret Moriarty, Helene J. Zirkle, Dorothy TI Challenges and Strategies When Context, Culture, and Time Affect Measurement in Family Research SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Horowitz, June Andrews; Hayes, Margaret; Zirkle, Dorothy] Boston Coll, Chestnut Hill, MA 02167 USA. [DuBois, Nancy] Thomas Jefferson Univ, Philadelphia, PA USA. [Moriarty, Helene J.] Philadelphia VA Med Ctr, Philadelphia, PA 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E41 EP E41 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300116 ER PT J AU Hoyt, A AF Hoyt, Alex TI Differences in Rates of Clinical Preventive Service Delivery between Nurses and Physicians; Results from a National Study SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Hoyt, Alex] Massachusetts Gen Hosp, Inst Hlth Profess, 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E27 EP E28 PG 2 WC Nursing SC Nursing GA 103WX UT WOS:000315951300076 ER PT J AU Jackson-Malik, P McLaughlin, M AF Jackson-Malik, Pamela McLaughlin, Mary TI Rapid Oral Fluid Testing for HIV in Veterans with Mental Health Diagnoses and Living in Community Assisted Living Residences SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Jackson-Malik, Pamela; McLaughlin, Mary] Philadelphia VA Med Ctr, Philadelphia, PA 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E106 EP E106 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300302 ER PT J AU Jones, DA Adams, J Ditomassi, M Duffy, M Erickson, JI AF Jones, Dorothy A. Adams, Jeffrey Ditomassi, Marianne Duffy, Mary Erickson, Jeanette Ives TI The Psychometric Evaluation of Three Measures of Professional Practice environments SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Jones, Dorothy A.] Boston Coll, Chestnut Hill, MA 02167 USA. [Jones, Dorothy A.; Adams, Jeffrey; Ditomassi, Marianne; Duffy, Mary; Erickson, Jeanette Ives] 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E14 EP E14 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300039 ER PT J AU Meisenhelder, JB D'Ambra, CJ AF Meisenhelder, Janice Bell D'Ambra, Charae J. TI Journaling as an Intervention: A Case Study of Spiritual Coping SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Meisenhelder, Janice Bell; D'Ambra, Charae J.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E16 EP E16 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300045 ER PT J AU Moriarty, HJ DeMarco, RF Horowitz, JA True, G Winter, L AF Moriarty, Helene J. DeMarco, Rosanna F. Horowitz, June Andrews True, Gala Winter, Laraine TI Using Qualitative Data to Understand and Inform Quantitative Data in Intervention Studies with Families SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Moriarty, Helene J.; Winter, Laraine] Philadelphia VA Med Ctr, Philadelphia, PA USA. [True, Gala] Philadelphia VA Med Ctr, CHERP, Philadelphia, PA USA. [DeMarco, Rosanna F.; Horowitz, June Andrews] Boston Coll, Chestnut Hill, MA 02167 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E42 EP E42 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300118 ER PT J AU Mylott, LA Banister, G Mulready-Schick, J AF Mylott, Laura A. Banister, Gaurdia Mulready-Schick, Joann TI Enriching Undergraduate Clinical Education: A Randomized Study Comparing a Dedicated Education Unit (DEU) With Traditional Clinical Education SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Mylott, Laura A.] Northeastern Univ, Boston, MA USA. [Banister, Gaurdia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mulready-Schick, Joann] UMASS Boston, 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E12 EP E12 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300033 ER PT J AU Shepard, M DeSanto-Madeya, S Horowitz, JA Moriarty, HJ AF Shepard, Margaret DeSanto-Madeya, Susan Horowitz, June Andrews Moriarty, Helene J. TI Emerging Research Methods That Are Responsive To Families And Communities SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Shepard, Margaret] UMDNJ, Newark, NJ USA. [DeSanto-Madeya, Susan] Univ Massachusetts Boston, Boston, MA USA. [Horowitz, June Andrews] Boston Coll, Chestnut Hill, MA 02167 USA. [Moriarty, Helene J.] Philadelphia VA Med Ctr, Philadelphia, PA 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 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E41 EP E41 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300115 ER PT J AU Underhill, M Crotser, C AF Underhill, Meghan Crotser, Cheryl TI Finding the Balance: Decision Support Needs of Women without a Cancer Diagnosis with a Known Hereditary Predisposition to Breast and Ovarian Cancer SO NURSING RESEARCH LA English DT Meeting Abstract C1 [Underhill, Meghan] U Mass Boston, Dana Farber Canc Inst, Boston, MA USA. [Crotser, Cheryl] Roberts Wesleyan Coll, Rochester, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAR-APR PY 2013 VL 62 IS 2 BP E52 EP E52 PG 1 WC Nursing SC Nursing GA 103WX UT WOS:000315951300145 ER PT J AU Hagstrom, SA Ying, GS Pauer, GJT Sturgill-Short, GM Huang, JY Callanan, DG Kim, IK Klein, ML Maguire, MG Martin, DF AF Hagstrom, Stephanie A. Ying, Gui-shuang Pauer, Gayle J. T. Sturgill-Short, Gwen M. Huang, Jiayan Callanan, David G. Kim, Ivana K. Klein, Michael L. Maguire, Maureen G. Martin, Daniel F. CA Comparison AMD Treatments Trials R TI Pharmacogenetics for Genes Associated with Age-related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT) SO OPHTHALMOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; INTRAVITREAL RANIBIZUMAB; POLYMORPHISM; BEVACIZUMAB; HTRA1; SUSCEPTIBILITY; Y402H AB Purpose: To evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment withranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD. Design: Clinical trial. Participants: Eight hundred thirty-four (73%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. Methods: Each patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). Main Outcomes Measures: Genotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, P <= 0.01 was considered statistically significant. Results: No statistically significant differences in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing. Conclusions: Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:593-599 (C) 2013 by the American Academy of Ophthalmology. C1 [Hagstrom, Stephanie A.; Pauer, Gayle J. T.; Sturgill-Short, Gwen M.; Martin, Daniel F.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44195 USA. [Hagstrom, Stephanie A.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Ophthalmol, Cleveland, OH 44106 USA. [Ying, Gui-shuang; Huang, Jiayan; Maguire, Maureen G.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Callanan, David G.] Texas Retina Associates, Arlington, TX USA. [Kim, Ivana K.] Harvard Univ, Sch Med, Dept Ophthalmol, Retina Serv,Massachusetts Eye & Ear Infirm, Boston, MA USA. [Klein, Michael L.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR USA. RP Hagstrom, SA (reprint author), Cleveland Clin, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM hagstrs@ccf.org FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [U10 EY017823, U10 EY017825, U10 EY017826, U10 EY017828] FX Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (cooperative agreement nos.: U10 EY017823, U10 EY017825, U10 EY017826, and U10 EY017828). The sponsor or funding organization had no role in the design or conduct of this research. NR 23 TC 68 Z9 71 U1 1 U2 40 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2013 VL 120 IS 3 BP 593 EP 599 DI 10.1016/j.ophtha.2012.11.037 PG 7 WC Ophthalmology SC Ophthalmology GA 100XJ UT WOS:000315738200025 PM 23337555 ER PT J AU Hong, JX Xu, JJ Hua, J Sun, XH AF Hong, Jiaxu Xu, Jianjiang Hua, Jing Sun, Xinghuai TI Bacterial Keratitis in Shanghai SO OPHTHALMOLOGY LA English DT Letter ID SHIFTING TRENDS; RESISTANCE C1 [Hong, Jiaxu; Xu, Jianjiang; Sun, Xinghuai] Fudan Univ, Sch Shanghai Med, Eye Ear Nose & Throat Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China. [Hua, Jing] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Hua, Jing] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Hong, JX (reprint author), Fudan Univ, Sch Shanghai Med, Eye Ear Nose & Throat Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China. OI Hong, Jiaxu/0000-0001-9912-633X NR 5 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2013 VL 120 IS 3 BP 647 EP 647 PG 1 WC Ophthalmology SC Ophthalmology GA 100XJ UT WOS:000315738200037 PM 23714610 ER PT J AU Oh, JE Cho, YW Scarcelli, G Kim, YH AF Oh, Joo-Eon Cho, Young-Wook Scarcelli, Giuliano Kim, Yoon-Ho TI Sub-Rayleigh imaging via speckle illumination SO OPTICS LETTERS LA English DT Article ID DIFFRACTION-LIMIT; RESOLUTION LIMIT; MICROSCOPY; LIGHT AB We demonstrate sub-Rayleigh limit imaging of an object via speckle illumination. Imaging beyond the conventional Rayleigh limit is achieved by illuminating the object with pseudothermal light that exhibits a random speckle pattern. An object image is reconstructed from the second-order correlation measurement and the resolution of the image, which exceeds the Rayleigh limit, is shown to be related to the size of the speckle pattern that is tied to the lateral coherence length of the pseudothermal light. (c) 2013 Optical Society of America C1 [Oh, Joo-Eon; Cho, Young-Wook; Kim, Yoon-Ho] Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, South Korea. [Scarcelli, Giuliano] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Scarcelli, Giuliano] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Kim, YH (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, South Korea. EM yoonho@postech.ac.kr RI Cho, Young-Wook/B-3124-2014; OI scarcelli, giuliano/0000-0002-1736-077X FU National Research Foundation [2011-0021452, 2012-002588]; National Junior Research Fellowship [2011-0010895]; Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; American Society for Laser Medicine and Surgery FX This work was supported in part by the National Research Foundation (2011-0021452 and 2012-002588). Y.-W.C. acknowledges support from National Junior Research Fellowship (2011-0010895). G. S. acknowledges support from the Harvard Clinical and Translational Science Center (NIH #UL1 RR 025758) and the American Society for Laser Medicine and Surgery. NR 22 TC 20 Z9 20 U1 0 U2 20 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 1 PY 2013 VL 38 IS 5 BP 682 EP 684 PG 3 WC Optics SC Optics GA 099EI UT WOS:000315602600029 PM 23455264 ER PT J AU Hoffmeister, P Gautam, S Peralta, A Kinlay, S AF Hoffmeister, Peter Gautam, Sandeep Peralta, Adelqui Kinlay, Scott TI Intravascular Ultrasound-Assisted Coronary Sinus Lead Implant in Patient with Contrast Anaphylaxis SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material DE CRT; imaging; pacing ID CARDIAC RESYNCHRONIZATION THERAPY; INTRACARDIAC ECHOCARDIOGRAPHY; INTERVENTIONS; ANGIOGRAPHY AB Ultrasound imaging has been used in a range of cardiac interventions. We describe the use of intravascular ultrasound to assist in coronary sinus lead implantation in a patient where contrast venography was contraindicated. (PACE 2013; 36:e74-e76) C1 [Hoffmeister, Peter; Gautam, Sandeep; Peralta, Adelqui] VA Boston Healthcare Syst, Dept Cardiac Pacing & Electrophysiol, West Roxbury, MA 02132 USA. [Hoffmeister, Peter] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. [Hoffmeister, Peter; Gautam, Sandeep; Peralta, Adelqui; Kinlay, Scott] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Cardiol, Boston, MA 02115 USA. [Kinlay, Scott] VA Boston Healthcare Syst, Dept Intervent Cardiol & Vasc Med, West Roxbury, MA 02132 USA. RP Hoffmeister, P (reprint author), VA Boston Healthcare Syst, Dept Cardiac Pacing & Electrophysiol, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM Peter.hoffmeister@va.gov OI Gautam, Sandeep/0000-0002-5629-0145 NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 EI 1540-8159 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAR PY 2013 VL 36 IS 3 BP e74 EP e76 DI 10.1111/j.1540-8159.2012.03361.x PG 3 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 102RL UT WOS:000315861600004 PM 22469186 ER PT J AU Duncan, CN Lehmann, LE Cheifetz, IM Greathouse, K Haight, AE Hall, MW Herschberger, A Hill, KS Moffet, JR Morrison, RR Norris, AL Petrovic, A Spear, DA Steiner, ME Talano, JAM Tamburro, RF Wagner, J McArthur, J AF Duncan, Christine N. Lehmann, Leslie E. Cheifetz, Ira M. Greathouse, Kristin Haight, Ann E. Hall, Mark W. Herschberger, Amber Hill, Katherine S. Moffet, Jerelyn R. Morrison, R. Ray Norris, Angela L. Petrovic, Aleksandra Spear, Debra A. Steiner, Marie E. Talano, Julie-An M. Tamburro, Robert F. Wagner, John McArthur, Jennifer CA Pediatric Acute Lung Injury Sepsis TI Clinical Outcomes of Children Receiving Intensive Cardiopulmonary Support During Hematopoietic Stem Cell Transplant SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE bone marrow transplantation; hematopoietic stem cell transplantation; ICU; mechanical ventilation; pediatrics; respiratory failure ID BONE-MARROW-TRANSPLANTATION; CARE-UNIT; REQUIRING ADMISSION; MECHANICAL VENTILATION; RESPIRATORY-FAILURE; HURLER-SYNDROME; RECIPIENTS; MORTALITY; SURVIVAL; PROGNOSIS AB Objective: We investigated the short-term and 1-year clinical outcomes of 129 children who received intensive cardiopulmonary support during hematopoietic stem cell transplant. Intensive cardiopulmonary support was defined as receiving at least one of the following interventions: continuous positive pressure ventilation, dopamine infusion greater than or equal to 10 mcg/kg/minute, or the use of any other vasoactive infusion. Duration of intensive cardiopulmonary support, survival to hospital discharge, and predictors of these outcome variables were compared with 387 hematopoietic stem cell transplant patients who did not receive intensive support during the same period. We also report the 1-year survival; presence of chronic graft-versus-host disease; and renal, cardiac, and pulmonary function for all patients. Design: A multicenter retrospective cohort study. Setting: The ICU and hematopoietic stem cell transplant unit of nine pediatric tertiary care centers. Patients: Children undergoing hematopoietic stem cell transplant who required intensive cardiopulmonary support. Interventions: None. Results: Predictors of the need for intensive support included unrelated donor allogeneic transplant, glomerular filtration rate less than 85 mL/minute/1.73 m(2), and nonmalignant disease as the indication for transplant. The survival to discontinuation of intensive support for all patients was 62% and 58% for patients who received invasive mechanical ventilatory support. The duration of mechanical ventilation was not predictive of survival. Predictors of intensive support mortality included macroscopic bleeding, engraftment, and pediatric logistic organ dysfunction score greater than one in two domains. Survival to hospital discharge was 50% for the intensive support group and 99% for the nonintensive support group. Overall 1-year survival was 40% in the intensive support population and 65% in the nonintensive support group. There were no significant differences in the survival, rates of chronic graft-versus-host disease, creatinine, forced expiratory volume in 1-minute, cardiac shortening fraction, or performance status in intensive and nonintensive support patients who survived to hospital discharge. Conclusion: Intensive cardiopulmonary support plays an important and potentially life-saving role in the care of pediatric stem cell transplant patients. Survivors of intensive support do not have compromised 1-year survival or organ function compared with children who did not receive intensive support. (Pediatr Crit Care Med 2013; 14:261-267) C1 [Duncan, Christine N.; Lehmann, Leslie E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Cheifetz, Ira M.; Moffet, Jerelyn R.] Duke Childrens Hosp, Dept Pediat, Durham, NC USA. [Greathouse, Kristin; Hall, Mark W.] Nationwide Childrens Hosp, Dept Crit Care Med, Columbus, OH USA. [Haight, Ann E.; Hill, Katherine S.] Childrens Healthcare Atlanta, Dept Pediat, Atlanta, GA USA. [Herschberger, Amber] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Oncol, Tampa, FL 33682 USA. [Morrison, R. Ray; Norris, Angela L.] St Jude Childrens Res Hosp, Dept Pediat Med, Memphis, TN 38105 USA. [Petrovic, Aleksandra] Univ S Florida, All Childrens Hosp, Dept Pediat, St Petersburg, FL 33701 USA. [Spear, Debra A.; Tamburro, Robert F.] Penn State Hershey Childrens Hosp, Dept Med, Hershey, PA USA. [Steiner, Marie E.; Wagner, John] Univ Minnesota, Dept Pediat, Childrens Hosp, Minneapolis, MN 55455 USA. [Talano, Julie-An M.; McArthur, Jennifer] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Duncan, CN (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM christine_duncan@dfci.-harvard.edu RI Hall, Mark/E-3193-2011 FU Medical College of Wisconsin; Dana-Farber Cancer Institution FX Supported, in part, by donation to the Dana-Farber Cancer Institution and the Medical College of Wisconsin institutional funds. NR 31 TC 13 Z9 13 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAR PY 2013 VL 14 IS 3 BP 261 EP 267 DI 10.1097/PCC.0b013e3182720601 PG 7 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 103WG UT WOS:000315949600010 PM 23392372 ER PT J AU Dylewksi, ML Baker, M Prelack, K Weber, JM Hursey, D Lydon, M Fagan, SP Sheridan, RL AF Dylewksi, Maggie L. Baker, Meghan Prelack, Kathy Weber, Joan M. Hursey, Derek Lydon, Martha Fagan, Shawn P. Sheridan, Robert L. TI The Safety and Efficacy of Parenteral Nutrition Among Pediatric Patients With Burn Injuries SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE burns; critical illness; enteral nutrition; hyperglycemia; infection; parenteral nutrition ID CRITICALLY-ILL PATIENTS; BLOOD-STREAM INFECTIONS; ENTERAL NUTRITION; MECHANICAL VENTILATION; TRAUMA PATIENTS; ADULT PATIENTS; CALORIC-INTAKE; ICU PATIENTS; METAANALYSIS; OUTCOMES AB Objective: Although enteral nutrition is the ideal mode of nutritional support following burn injury, it is often interrupted during episodes of severe sepsis and hemodynamic instability, leading to significant energy and protein deficits. Parenteral nutrition is not commonly used in burn centers due to concerns that it will lead to hyperglycemia, infection, and increased mortality. However, parenteral nutrition is often utilized in our burn unit when goal rate enteral nutrition is not feasible. To determine the safety and efficacy of a standardized protein-sparing parenteral nutrition protocol in which glucose infusion is limited to 5-7 mg/kg/hour. Design: Retrospective observational study. Setting: Pediatric burn hospital. Patients: A retrospective medical record review of all children admitted to our hospital with burns >= 30% total body surface area was conducted. Only patients admitted within one week of injury and who survived > 24 hours after admission were included in this study. Interventions: None. Measurements and Main Results: Of the 105 patients who met the inclusion criteria, 96 (91%) received parenteral nutrition or a combination of parenteral nutrition and enteral nutrition at some point during their care. Nine patients received only enteral nutrition. Demographic data were similar between groups. Protein intake was significantly higher in the parenteral nutrition group. Incidence of catheter-related blood infections did not differ between groups. Use of parenteral nutrition was not associated with blood or respiratory infections. Overall mortality rate was low (4%), as most patients (96%) achieved wound closure and were discharged home. Conclusions: Judicious use of parenteral nutrition is a safe and effective means of nutritional support when goal enteral nutrition cannot be achieved. A hypocaloric, high-nitrogen parenteral nutrition solution can reduce energy and protein deficits while minimizing complications commonly associated with parenteral nutrition usage. (Pediatr Crit Care Med 2013; 14:e120-e125) C1 [Dylewksi, Maggie L.; Prelack, Kathy; Weber, Joan M.; Hursey, Derek; Lydon, Martha; Fagan, Shawn P.; Sheridan, Robert L.] Shriners Hosp Children, Boston, MA USA. [Baker, Meghan; Fagan, Shawn P.; Sheridan, Robert L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dylewksi, ML (reprint author), Shriners Hosp Children, Boston, MA USA. EM mdylewski@shrinenet.org NR 35 TC 3 Z9 3 U1 0 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAR PY 2013 VL 14 IS 3 BP E120 EP E125 DI 10.1097/PCC.0b013e3182712b2b PG 6 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 103WG UT WOS:000315949600001 PM 23392358 ER PT J AU Balk, SJ Fisher, DE Geller, AC AF Balk, Sophie J. Fisher, David E. Geller, Alan C. TI Stronger Laws Are Needed to Protect Teens From Indoor Tanning SO PEDIATRICS LA English DT Editorial Material DE indoor tanning; artificial tanning; tanning legislation; teenagers; skin cancer; melanoma; prevention; tanning legislation ID CUTANEOUS MELANOMA; RISK; SUN C1 [Balk, Sophie J.] Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA. [Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Balk, SJ (reprint author), 1621 Eastchester Rd, Bronx, NY 10461 USA. EM sbalk@montefiore.org FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 20 TC 4 Z9 4 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2013 VL 131 IS 3 BP 586 EP 588 DI 10.1542/peds.2012-3367 PG 3 WC Pediatrics SC Pediatrics GA 098ZI UT WOS:000315587400064 PM 23439900 ER PT J AU Kriska, A Delahanty, L Edelstein, S Amodei, N Chadwick, J Copeland, K Galvin, B El Ghormli, L Haymond, M Kelsey, M Lassiter, C Mayer-Davis, E Milaszewski, K Syme, A AF Kriska, Andrea Delahanty, Linda Edelstein, Sharon Amodei, Nancy Chadwick, Jennifer Copeland, Kenneth Galvin, Bryan El Ghormli, Laure Haymond, Morey Kelsey, Megan Lassiter, Chad Mayer-Davis, Elizabeth Milaszewski, Kerry Syme, Amy TI Sedentary Behavior and Physical Activity in Youth With Recent Onset of Type 2 Diabetes SO PEDIATRICS LA English DT Article DE inactivity; accelerometer; adolescence; obesity; movement ID ADOLESCENT GIRLS; FITNESS; AGE AB OBJECTIVE: With the rise of type 2 diabetes in youth, it is critical to investigate factors such as physical activity (PA) and time spent sedentary that may be contributing to this public health problem. This article describes PA and sedentary time in a large cohort of youth with type 2 diabetes and compares these levels with other large-scale investigations. METHODS: The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial is a study in 699 youth, recruited from 15 US clinical centers, aged 10 to 17 years with <2 years of type 2 diabetes and a BMI >= 85th percentile. RESULTS: In comparison with the subset of the NHANES cohort who were obese (BMI >= 95th percentile), TODAY youth spent significantly more time being sedentary (difference averaging 56 minutes per day; P<.001) as assessed by accelerometry. Although moderate to vigorous activity levels in both obese cohorts for all age groups were exceptionally low, younger TODAY boys were still significantly less active than similarly aged NHANES youth. Comparisons between the TODAY girls and other investigations suggest that the TODAY girls also had relatively lower PA and fitness levels. CONCLUSIONS: Adolescents with type 2 diabetes from the large TODAY cohort appear to be less physically active and tend to spend more time being sedentary than similarly aged youth without diabetes identified from other large national investigations. Treatment efforts in adolescents with type 2 diabetes should include decreasing sitting along with efforts to increase PA levels. Pediatrics 2013;131:e850-e856 C1 [Kriska, Andrea] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Delahanty, Linda] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Edelstein, Sharon; El Ghormli, Laure] George Washington Univ, Biostat Ctr, Rockville, MD 20852 USA. [Amodei, Nancy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Chadwick, Jennifer; Copeland, Kenneth] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Galvin, Bryan] Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Pittsburgh, PA USA. [Haymond, Morey] Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Kelsey, Megan] Univ Colorado Denver, Childrens Hosp Colorado, Aurora, CO USA. [Lassiter, Chad] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Mayer-Davis, Elizabeth] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Milaszewski, Kerry] Joslin Diabet Ctr, Boston, MA 02215 USA. [Syme, Amy] Yale Univ, Sch Med, Dept Pediat Endocrinol, New Haven, CT USA. RP El Ghormli, L (reprint author), George Washington Univ, Biostat Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM elghorml@bsc.gwu.edu OI Kriska, Andrea/0000-0002-3522-0869 FU Daichii Sankyo; Bristol-Myers Squibb; Merck FX Dr Copeland is on the National Advisory Committee and a consultant with Honoraria to Novo Nordisk and Daiichi Sankyo Inc; Dr Kelsey is an investigator for type 2 diabetes sponsored by Daichii Sankyo, Bristol-Myers Squibb, and Merck; Ms Milaszewski is a consultant for Medtronic insulin pumps; the other authors have indicated they have no financial relationships relevant to this article to disclose. NR 19 TC 24 Z9 24 U1 2 U2 20 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2013 VL 131 IS 3 BP E850 EP E856 DI 10.1542/peds.2012-0620 PG 7 WC Pediatrics SC Pediatrics GA 098ZI UT WOS:000315587400025 PM 23400602 ER PT J AU Eberlin, KR Hartzell, TL Kuo, P Winograd, J Day, C AF Eberlin, Kyle R. Hartzell, Tristan L. Kuo, Phoebe Winograd, Jonathan Day, Charles TI Patients Transferred for Emergency Upper Extremity Evaluation: Does Insurance Status Matter? SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID I TRAUMA CENTER; ORTHOPEDIC INJURIES; SYSTEM; TRIAGE; CARE AB Background: Academic institutions receive many patients transferred specifically for hand surgery evaluation. The purpose of this study was to evaluate the demographics and insurance status of patients transferred for this reason. Methods: A retrospective review was performed of 155 transferred and 1017 nontransferred patients with a primary hand diagnosis during 3 summermonths at two urban academic institutions. Patients were evaluated for insurance status/type, medical comorbidities, employment status, and reason for transfer. Insurance was defined as present/absent and favorable/unfavorable, with unfavorable defined as Medicaid or state-sponsored insurance. Reason for transfer or presenting diagnosis was separated by category. Results: The mean age was similar between groups, but a higher percentage of transfer patients were men (69.9 percent versus 59.7 percent; p < 0.05). The percentage of insured patients was similar (92.9 percent versus 93.2 percent), but the number with no insurance or undesirable insurance was greater for transferred patients (30.1 percent versus 22.9 percent; p < 0.05). Patients with poor or no insurance were twice as likely to be inappropriately transferred (OR, 2.17; p < 0.03). Transferred patients were less likely to be employed (55.1 percent versus 64.8 percent; p < 0.05); however, the percentages of workers' compensation (13.5 percent versus 14.6 percent) and diabetes (6.41 percent versus 6.10 percent) cases were similar. Common reasons for transfer were closed fractures/dislocations (21.9 percent), infection (17.4 percent), and amputation/devascularization (17.4 percent). Conclusion: Patients transferred to tertiary care centers for emergency upper extremity evaluation have a higher rate of undesirable or no insurance and are more likely to be male or unemployed. (Plast. Reconstr. Surg. 131: 593, 2013.) C1 Harvard Univ, Div Plast Surg, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Dept Orthoped Surg, Beth Israel Deaconess Med Ctr, Sch Med, Cambridge, MA 02138 USA. RP Eberlin, KR (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 55 Fruit St,WACC 435, Boston, MA 02114 USA. EM keberlin@partners.org NR 23 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2013 VL 131 IS 3 BP 593 EP 600 DI 10.1097/PRS.0b013e31827c6e82 PG 8 WC Surgery SC Surgery GA 098UA UT WOS:000315573400065 PM 23446571 ER PT J AU Nickerson, A Bryant, RA Aderka, IM Hinton, DE Hofmann, SG AF Nickerson, Angela Bryant, Richard A. Aderka, Idan M. Hinton, Devon E. Hofmann, Stefan G. TI The Impacts of Parental Loss and Adverse Parenting on Mental Health: Findings From the National Comorbidity Survey-Replication SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE parent death; parenting; depression; anxiety; mental health ID ADULT PSYCHIATRIC-DISORDERS; DSM-IV-DISORDERS; CHILDHOOD ADVERSITIES; NCS-R; MAJOR DEPRESSION; SOCIAL SUPPORT; ELDERLY PARENT; SELF-ESTEEM; DEATH; ANXIETY AB There has been much controversy regarding the psychological impact of the death of a parent, partly arising from neglect of potential moderating factors. The present study uses data from the National Comorbidity Survey Replication (NCS-R) to investigate the relative impacts of age at death of parent, adverse parenting practices, and time since loss on mental health outcomes in 2,823 bereaved adults. Logistic regression analyses controlling for sex and race revealed that younger age at the time of parental death was associated with poorer mental health outcomes. Further, adverse parenting practices during childhood were related to greater psychopathology in adulthood. Results also indicated that psychological distress following the death of a parent reduces over time. Notably, each of these factors significantly predicted psychopathology when controlling for all other variables. Findings are discussed in the context of current theories of attachment and psychopathology. C1 [Nickerson, Angela] Massachusetts Vet Epidemiol Res & Informat Ctr, Sydney, NSW, Australia. [Nickerson, Angela; Bryant, Richard A.] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia. [Aderka, Idan M.; Hofmann, Stefan G.] Boston Univ, Psychotherapy & Emot Res Lab, Boston, MA 02215 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Nickerson, A (reprint author), Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia. EM a.nickerson@unsw.edu.au RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Bryant, Richard/0000-0002-9607-819X NR 59 TC 5 Z9 5 U1 0 U2 30 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2013 VL 5 IS 2 BP 119 EP 127 DI 10.1037/a0025695 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 102JP UT WOS:000315841200003 ER PT J AU Iverson, KM Bauer, MR Shipherd, JC Pineles, SL Harrington, EF Resick, PA AF Iverson, Katherine M. Bauer, Margaret R. Shipherd, Jillian C. Pineles, Suzanne L. Harrington, Ellen F. Resick, Patricia A. TI Differential Associations Between Partner Violence and Physical Health Symptoms Among Caucasian and African American Help-Seeking Women SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE race; women; partner violence; physical health; moderation ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL SUPPORT; BATTERED WOMEN; SEXUAL-HARASSMENT; BLACK; SPIRITUALITY; EXPERIENCES; SURVIVORS; CONFLICT; OUTCOMES AB The relationship between partner violence and physical health symptoms is well-established. Although some researchers have theorized that the physical health effects of partner violence may be worse for ethnic minority women, there is little research addressing this topic. The current study examined whether African American women demonstrate a differential association in this relationship than Caucasian women. This study included 323 women (232 African American, 91 Caucasian) who participated in a larger investigation of the psychological and psychophysiological correlates of recent partner violence among women seeking help for the abuse. Race was examined as a moderator of the relationship between partner violence frequency and physical health symptoms. Although mean levels of partner violence frequency and physical health symptoms did not significantly differ between African American and Caucasian women, linear regression analyses demonstrated a significant positive relationship between partner violence frequency and physical health symptoms for African American women; whereas there was no association observed between these variables for Caucasian women. Post hoc analyses revealed that posttraumatic stress disorder symptoms partially mediated the association between partner violence frequency and physical health symptoms for the African American women. The current findings underscore the importance of considering race when studying the effect of partner violence on women's health. C1 [Iverson, Katherine M.; Bauer, Margaret R.; Shipherd, Jillian C.; Pineles, Suzanne L.; Resick, Patricia A.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Iverson, Katherine M.; Shipherd, Jillian C.; Pineles, Suzanne L.; Resick, Patricia A.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Harrington, Ellen F.] Summa Hlth Syst, Ctr Treatment & Study Traumat Stress, Akron, OH USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Iverson, KM (reprint author), WHSD VA Boston Healthcare Syst, 150 South Huntington Ave,116B-3, Boston, MA 02130 USA. EM Katherine.Iverson@va.gov FU NIMH NIH HHS [R01 MH055542, R01 MH055542-03] NR 59 TC 3 Z9 3 U1 4 U2 10 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2013 VL 5 IS 2 BP 158 EP 166 DI 10.1037/a0025912 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 102JP UT WOS:000315841200008 PM 23616911 ER PT J AU Sloan, DM Feinstein, BA Gallagher, MW Beck, JG Keane, TM AF Sloan, Denise M. Feinstein, Brian A. Gallagher, Matthew W. Beck, J. Gayle Keane, Terence M. TI Efficacy of Group Treatment for Posttraumatic Stress Disorder Symptoms: A Meta-Analysis SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE group treatment; PTSD; trauma; meta-analysis ID CHILDHOOD SEXUAL-ABUSE; FOCUSED GROUP-THERAPY; RANDOMIZED-TRIAL; WOMEN; MANAGEMENT; VETERANS; PTSD; PSYCHOTHERAPY; GUIDELINES; EXPOSURE AB This study conducted a meta-analysis of published randomized clinical group trials for adult survivors of trauma to examine the efficacy of the group format. Effect sizes for posttraumatic stress disorder (PTSD) severity outcome were examined. Sixteen studies were included, with a total of 1686 participants. Results of a random effects model meta-analysis indicated that group treatments are associated with significant pre- to posttreatment reduction in PTSD symptom severity (within treatment d = .71, 95% CI [.51, .91]), and result in superior treatment effects relative to a wait list comparison condition (d = .56, 95% CI [.31, .82]). However, no significant findings were obtained for group interventions relative to active treatment comparison conditions (d = .09, 95% CI [-.03, .22]). Moderator analyses also indicated that gender and type of trauma moderated treatment effects for PTSD outcome, with smaller effect sizes associated with males relative to females and combined gender samples, and smaller effect sizes for combat and child sexual assault trauma samples relative to mixed-trauma sample studies. Taken together, group treatment for trauma symptoms is better than no treatment but not better relative to comparison conditions that control for nonspecific benefits of therapy. Additional work is needed to identify effective group treatments for PTSD, especially for patients with repeated or chronic traumatization. C1 [Sloan, Denise M.; Gallagher, Matthew W.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Sloan, Denise M.; Gallagher, Matthew W.; Keane, Terence M.] Boston Univ, Behav Sci Div, Boston, MA 02215 USA. [Feinstein, Brian A.] SUNY Stony Brook, Deparment Psychol, Stony Brook, NY USA. [Beck, J. Gayle] Univ Memphis, Deparment Psychol, Memphis, TN 38152 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov NR 37 TC 21 Z9 21 U1 3 U2 30 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2013 VL 5 IS 2 BP 176 EP 183 DI 10.1037/a0026291 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 102JP UT WOS:000315841200010 ER PT J AU Bonn-Miller, MO Boden, MT Vujanovic, AA Drescher, KD AF Bonn-Miller, Marcel O. Boden, Matthew Tyler Vujanovic, Anka A. Drescher, Kent D. TI Prospective Investigation of the Impact of Cannabis Use Disorders on Posttraumatic Stress Disorder Symptoms Among Veterans in Residential Treatment SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; PTSD; trauma; cannabis; marijuana ID SUBSTANCE USE DISORDERS; USE COPING MOTIVES; MARIJUANA USE; PSYCHOMETRIC PROPERTIES; PTSD CHECKLIST; ABUSE; VALIDITY; SAMPLE AB This investigation sought to provide the first prospective examination of the association between the presence of a current cannabis use disorder (CUD) diagnosis and changes in posttraumatic stress disorder (PTSD) symptoms over time after discontinuation, after accounting for the theoretically relevant effects of age, trauma severity, psychological distress, and co-occurring substance use disorders. The study was longitudinal and assessed clinical patients at two time points: residential PTSD treatment intake and discharge. The sample consisted of 260 male combat-exposed military veteran patients (M-age = 52.57 years, SD = 5.47) admitted to a Veterans Affairs residential rehabilitation program for PTSD between 2000 and 2008. Diagnoses were obtained using the Structured Clinical Interview for DSM-IV, and PTSD outcomes were determined by the PTSD Checklist-Military Version. Results indicate that the presence of a CUD diagnosis was significantly predictive of lower levels of change (between treatment intake and discharge) in PTSD symptom severity as well as PTSD avoidance-numbing and hyperarousal symptom cluster severity (all ps < .05). This study presents the first evidence of a prospective relation between problematic cannabis use and PTSD symptoms, indicating that individuals with a CUD are likely to experience lower levels of change in PTSD symptoms over time, within the context of discontinuation owing to residential PTSD treatment. C1 [Bonn-Miller, Marcel O.; Drescher, Kent D.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.; Boden, Matthew Tyler] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Vujanovic, Anka A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Bonn-Miller, MO (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM Marcel.Bonn-Miller@va.gov NR 36 TC 13 Z9 13 U1 0 U2 12 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2013 VL 5 IS 2 BP 193 EP 200 DI 10.1037/a0026621 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 102JP UT WOS:000315841200012 ER PT J AU Kontos, N Freudenreich, O Querques, J AF Kontos, Nicholas Freudenreich, Oliver Querques, John TI Beyond Capacity: Identifying Ethical Dilemmas Underlying Capacity Evaluation Requests SO PSYCHOSOMATICS LA English DT Article ID DECISION-MAKING CAPACITY; COMPETENCE EVALUATIONS; HATEFUL PATIENT; MEDICAL-ETHICS; HEALTH-CARE; CONSULTATION; AUTONOMY; RESPONSIBILITY; PSYCHIATRY; EXPERTISE AB Background: Psychiatric consultations involving the evaluation of patients' medical decision-making capacity often seem to have little to do with truly compromised patient autonomy. Objective: The authors seek to examine hidden ethical dilemmas that lead to capacity evaluation requests. Method: The authors utilize the "principlism" approach to biomedical ethics to illustrate some common moral issues in patient care that are poorly captured by the "autonomy-versus-paternalism" paradigm. Results: Patient autonomy sometimes comes into conflict with ethical imperatives to do "good," to avoid harm, and to deliver care fairly, as well as with the autonomy of others. Consultation psychiatrists are well positioned to unearth these dilemmas and begin to address them. Discussion: Effective engagement of everyday ethics in clinical medicine is hindered by reflexive resort to capacity evaluations when moral problems arise. Greater attention to matters of values, aggressive urges, and obligations to others can enhance the negotiation of routine ethical dilemmas. (Psychosomatics 2013; 54:103-110) C1 [Kontos, Nicholas; Freudenreich, Oliver; Querques, John] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kontos, Nicholas; Freudenreich, Oliver; Querques, John] Harvard Univ, Sch Med, Boston, MA USA. RP Kontos, N (reprint author), Massachusetts Gen Hosp, Psychiat Consultat Serv, 55 Fruit St,Warren 605, Boston, MA 02114 USA. EM nkontos@partners.org NR 64 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2013 VL 54 IS 2 BP 103 EP 110 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 104ET UT WOS:000315975300001 PM 23218060 ER PT J AU Park, ER Traeger, L Vranceanu, AM Scutt, M Lerner, JA Benson, H Denninger, J Fricchione, GL AF Park, Elyse R. Traeger, Lara Vranceanu, Ana-Maria Scutt, Matthew Lerner, Jonathan A. Benson, Herbert Denninger, John Fricchione, Gregory L. TI The Development of a Patient-Centered Program Based on the Relaxation Response: The Relaxation Response Resiliency Program (3RP) SO PSYCHOSOMATICS LA English DT Article ID BEHAVIORAL MEDICINE INTERVENTION; MIND-BODY MEDICINE; WORKING POPULATION; SYMPTOM REDUCTION; ALLOSTATIC LOAD; STRESS; MEDITATION; HEALTH; ADAPTATION; MANAGEMENT AB Background: Chronic daily stress has significant physical, emotional, and financial implications; levels of stress are increasing in the US. Dr. Benson highlighted how the mind and body function together in one's experience of the stress response and proposed the existence of the relaxation response (RR). Objective: The current paper describes the foundation and development of an 8-session multimodal treatment program for coping with chronic stress: the Relaxation Response Resiliency Program (3RP). Methods: We review the past decades of RR research, outline the development of the 3RP treatment, and provide an overview of the program's theory and content. Results: Extensive research and clinical work have examined how eliciting the RR may combat stress through down-regulation of the sympathetic nervous system. Related to this work are the multidimensional constructs of resiliency and allostatic load. The 3RP is based on principles from the fields of stress management, cognitive-behavioral therapy, and positive psychology, and has three core target areas: (1) elicitation of the RR; (2) stress appraisal and coping; and (3) growth enhancement. An 8-week patient-centered treatment program has been developed, with the purpose of assisting patients with a variety of psychological and medical issues to better cope with chronic stress. Conclusions: Mastery of the RR is theorized to maximize one's ability to benefit from multimodal mind body strategies. The goal of the 3RP is to enhance individuals' adaptive responses to chronic stress through increasing awareness and decreasing the physiological, emotional, cognitive, and behavioral effects of the stress response, while simultaneously promoting the effects of being in the RR. (Psychosomatics 2013; 54:165-174) C1 [Park, Elyse R.; Traeger, Lara; Vranceanu, Ana-Maria; Scutt, Matthew; Lerner, Jonathan A.; Benson, Herbert; Denninger, John; Fricchione, Gregory L.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Park, Elyse R.; Traeger, Lara; Vranceanu, Ana-Maria; Lerner, Jonathan A.; Benson, Herbert; Denninger, John; Fricchione, Gregory L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM epark@partners.org OI Scult, Matthew/0000-0001-5554-8186 FU Center for Disease Control and Prevention [R01DP000339] FX This work was supported by the Center for Disease Control and Prevention (Grant R01DP000339). NR 55 TC 17 Z9 17 U1 3 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2013 VL 54 IS 2 BP 165 EP 174 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 104ET UT WOS:000315975300009 PM 23352048 ER PT J AU Alfson, ED Awosika, OO Singhal, T Fricchione, GL AF Alfson, Elizabeth D. Awosika, Oluwole O. Singhal, Tarun Fricchione, Gregory L. TI Lysis of Catatonic Withdrawal by Propofol in a Bone-Marrow Transplant Recipient with Adenovirus Limbic Encephalitis SO PSYCHOSOMATICS LA English DT Article ID RELEASE; SYNAPTOSOMES; ANESTHETICS; THERAPY C1 [Alfson, Elizabeth D.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Alfson, Elizabeth D.; Awosika, Oluwole O.; Singhal, Tarun] Harvard Univ, Sch Med, Boston, MA USA. [Awosika, Oluwole O.; Singhal, Tarun] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Fricchione, Gregory L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Alfson, ED (reprint author), Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. EM ealfson@partners.org NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2013 VL 54 IS 2 BP 192 EP 195 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 104ET UT WOS:000315975300013 PM 22705183 ER PT J AU Royer, HR Falk, EC Heidrich, SM AF Royer, Heather R. Falk, Elizabeth C. Heidrich, Susan M. TI Sexually Transmitted Disease Testing Misconceptions Threaten the Validity of Self-Reported Testing History SO PUBLIC HEALTH NURSING LA English DT Article DE beliefs; screening; sexually transmitted diseases; women's health ID UNITED-STATES; YOUNG-WOMEN; CHLAMYDIA; STIGMA; ADOLESCENTS; INFECTIONS; PREVALENCE; KNOWLEDGE; GONORRHEA; HEALTH AB Objective Sexually transmitted disease (STD) testing is fundamental to STD prevention and control. We sought to comprehensively examine young women's beliefs about the STD testing process. Design and Sample Descriptive, cross-sectional, survey investigation. Women aged 1824 (n=302) drawn from four women's health clinics and one university classroom. Measures Participants completed the RoTEST, which measures five domains of women's STD testing beliefs and a demographic survey. Results Many women believed they would be screened for all STDs when they receive STD testing (40%) and that visual inspection by a provider was a valid method of STD screening for gonorrhea (35%), chlamydia (32%) and HSV (77%). More than a quarter believed that a Pap test screens for gonorrhea (23%) and chlamydia (26%). Twenty-one percent reported that discussing STD testing with a provider is difficult and most reported feeling more comfortable seeking STD testing from an STD specialist rather than a family doctor (79%). Conclusions Young women have numerous misconceptions about the STD testing process that may interfere with the validity of their self-reported STD testing history and subsequently undermine public health efforts to improve STD prevention and control. Innovative approaches to educating women about the testing process are needed. C1 [Royer, Heather R.] Univ Wisconsin Milwaukee, Coll Nursing, Milwaukee, WI USA. [Falk, Elizabeth C.] Univ Wisconsin Whitewater, Univ Hlth & Counseling Serv, Whitewater, WI USA. [Heidrich, Susan M.] Univ Wisconsin Madison, Sch Nursing, Madison, WI USA. [Heidrich, Susan M.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. RP Royer, HR (reprint author), 1921 E Hartford Ave, Milwaukee, WI 53211 USA. EM hrroyer@uwm.edu NR 23 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0737-1209 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD MAR-APR PY 2013 VL 30 IS 2 BP 117 EP 127 DI 10.1111/phn.12013 PG 11 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA 100BK UT WOS:000315669500004 PM 23452106 ER PT J AU Roffman, JL Brohawn, DG Nitenson, AZ Macklin, EA Smoller, JW Goff, DC AF Roffman, Joshua L. Brohawn, David G. Nitenson, Adam Z. Macklin, Eric A. Smoller, Jordan W. Goff, Donald C. TI Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE gene-environment interaction; methylation; epigenetics; genetic risk score ID CATECHOL-O-METHYLTRANSFERASE; ONE-CARBON METABOLISM; METHYLENETETRAHYDROFOLATE REDUCTASE; RISK-FACTOR; HOMOCYSTEINE LEVELS; DNA-METHYLATION; COMMON MUTATION; BLADDER-CANCER; POLYMORPHISMS; DEPRESSION AB Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients. C1 [Roffman, Joshua L.; Brohawn, David G.; Nitenson, Adam Z.; Smoller, Jordan W.; Goff, Donald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Macklin, Eric A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 2606, Charlestown, MA 02129 USA. EM jroffman@partners.org RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 FU Harvard-Massachusetts Institute of Technology Division of Health Science and Technology Clinical Investigator Training Program; Howard Hughes Medical Institute Early Career Physician Scientist Award; Charles King Trust/Campbell and Hall/Alden Trust; National Institute of Mental Health [MH079799, MH0060450, MH070831, MH002025]; NARSAD Independent Investigator Award; PamLab; Pfizer; Janssen; Novartis; GlaxoSmithKline; Harvard-MIT Division of Health Sciences Clinical Investigator Training Program; Merck FX Harvard-Massachusetts Institute of Technology Division of Health Science and Technology Clinical Investigator Training Program, Howard Hughes Medical Institute Early Career Physician Scientist Award, and Charles King Trust/Campbell and Hall/Alden Trust (to J.L.R.); National Institute of Mental Health (MH079799 to J.W.S. and MH0060450, MH070831, MH002025 to D.C.G.) and a NARSAD Independent Investigator Award to D.C.G.; Disclosures: Drs D.C.G. and J.L.R. have submitted a US patent application concerning the effects of MTHFR, MTR, and FOLH1 on response to folate supplementation in schizophrenia. Dr D.C.G. reports having served as a consultant or advisor to: Xytis, Forest Labs, Pfizer, Indevus Pharmaceuticals, H. Lundbeck, Schering-Plough, Eli Lilly, Takeda, Biovail, Solvay, Hoffman-La Roche, Cypress, and Dainippon Sumitomo. He received grant support from PamLab, Pfizer, Janssen, Novartis, and GlaxoSmithKline Dr J.L.R. has received fellowship support from the Harvard-MIT Division of Health Sciences Clinical Investigator Training Program, which receives funding through unrestricted educational grants from Merck and Pfizer. No other authors report biomedical financial interests or potential conflicts of interest. Presented in part at the American College of Neuropsychopharmacology 2009 Annual Meeting. NR 42 TC 18 Z9 18 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2013 VL 39 IS 2 BP 330 EP 338 DI 10.1093/schbul/sbr150 PG 9 WC Psychiatry SC Psychiatry GA 098NV UT WOS:000315556900017 PM 22021659 ER PT J AU Wiener, H Klei, L Calkins, M Wood, J Nimgaonkar, V Gur, R Bradford, LD Richard, J Edwards, N Savage, R Kwentus, J Allen, T McEvoy, J Santos, A Gur, R Devlin, B Go, R AF Wiener, Howard Klei, Lambertus Calkins, Monica Wood, Joel Nimgaonkar, Vishwajit Gur, Ruben Bradford, L. DiAnne Richard, Jan Edwards, Neil Savage, Robert Kwentus, Joseph Allen, Trina McEvoy, Joseph Santos, Alberto Gur, Raquel Devlin, Bernie Go, Rodney TI Principal Components of Heritability From Neurocognitive Domains Differ Between Families With Schizophrenia and Control Subjects SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; cognition; heritability; principal components; linkage ID RECURRENT MICRODELETIONS; AFRICAN-AMERICANS; PSYCHOSIS VARIANT; LINKAGE ANALYSIS; EXPLORE RISKS; CHILDHOOD; ZNF804A; MEMORY; IMPAIRMENT; PROJECT AB Objective: Various measures of neurocognitive function show mean differences among individuals with schizophrenia (SZ), their relatives, and population controls. We use eigenvector transformations that maximize heritability of multiple neurocognitive measures, namely principal components of heritability (PCH), and evaluate how they distribute in SZ families and controls. Methods: African-Americans with SZ or schizoaffective disorder (SZA) (n = 514), their relatives (n = 1092), and adult controls (n = 300) completed diagnostic interviews and computerized neurocognitive tests. PCH were estimated from 9 neurocognitive domains. Three Pd, PCH1-PCH3, were modeled to determine if status (SZ, relative, and control), other psychiatric covariates, and education were significant predictors of mean values. A small-scale linkage analysis was also conducted in a subset of the sample. Results: PCH1, PCH2, and PCH3 account for 72% of the genetic variance. PCH1 represents 8 of 9 neurocognitive domains, is most highly correlated with spatial processing and emotion recognition, and has unadjusted heritability of 68%. The means for PCH1 differ significantly among SZ, their relatives, and controls. PCH2, orthogonal to PCH1, is most closely correlated with working memory and has an unadjusted heritability of 45%. Mean PCH2 is different only between SZ families and controls. PCH3 apparently represents a heritable component of neurocognition similar across the 3 diagnostic groups. No significant linkage evidence to PCH1-PCH3 or individual neurocognitive measures was discovered. Conclusions: PCH1 is highly heritable and genetically correlated with SZ. It should prove useful in future genetic analyses. Mean PCH2 differentiates SZ families and controls but not SZ and unaffected family members. C1 [Wiener, Howard; Go, Rodney] Univ Alabama Birmingham, Dept Epidemiol & Int Hlth, Birmingham, AL USA. [Klei, Lambertus; Wood, Joel; Nimgaonkar, Vishwajit; Devlin, Bernie] Univ Pittsburgh Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. [Calkins, Monica; Gur, Ruben; Richard, Jan; Gur, Raquel] Univ Penn, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Nimgaonkar, Vishwajit; Devlin, Bernie] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Gur, Ruben] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Bradford, L. DiAnne] Morehouse Sch Med, Dept Psychiat, Atlanta, GA 30310 USA. [Edwards, Neil] Univ Tennessee, Coll Med, Dept Psychiat, Memphis, TN USA. [Savage, Robert] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL USA. [Kwentus, Joseph] Univ Mississippi Med Ctr, Dept Psychiat & Human Behav, Jackson, MS USA. [Allen, Trina; McEvoy, Joseph] Duke Univ Med Ctr, John Umstead Hosp, Butner, NC USA. [Santos, Alberto] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Devlin, B (reprint author), Western Psychiat Inst & Clin, Computat Genet Program, Room 430,Oxford Bldg,3501 Forbes Ave, Pittsburgh, PA 15213 USA. EM devlinbj@upmc.edu FU National Institute of Mental Health [MH066006, MH066278, MH066049, MH066181, MH066121, MH066005, MH066050, MH066263, MH066004, K08MH79364]; National Institute of Mental Health; federal contract from the National Institutes of Health [HHSN268200782096C]; University of Pennsylvania; AstraZeneca; Pfizer; Merck; University of Mississippi; Eli Lilly; Bristol Meyers; Johnson Johnson; Takeda FX This work was supported by the National Institute of Mental Health (MH066006, MH066278, MH066049, MH066181, MH066121, MH066005, MH066050, MH066263, MH066004, and K08MH79364). The National Institute of Mental Health also provided funding to pay for Open Access. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. University of Pennsylvania with AstraZeneca, Pfizer, and Merck (to Ru.G.). University of Mississippi with Eli Lilly, AstraZeneca, Pfizer, Bristol Meyers, Johnson & Johnson and Takeda (to J.K.). University of Pennsylvania with AstraZeneca and Pfizer. (Dr Ra.G.) Drs Ru.G. and Ra.G. and Ms J.R. may receive royalties from future commercial use of the Penn Computerized Neurocognitive Battery. NR 40 TC 5 Z9 5 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2013 VL 39 IS 2 BP 464 EP 471 DI 10.1093/schbul/sbr161 PG 8 WC Psychiatry SC Psychiatry GA 098NV UT WOS:000315556900029 PM 22234486 ER PT J AU Christov, M Juppner, H AF Christov, Marta Jueppner, Harald TI Insights From Genetic Disorders of Phosphate Homeostasis SO SEMINARS IN NEPHROLOGY LA English DT Review DE FGF23; hypophosphatemic rickets; renal phosphate transport; phosphate control ID FIBROBLAST GROWTH FACTOR-23; HEREDITARY HYPOPHOSPHATEMIC RICKETS; FAMILIAL TUMORAL CALCINOSIS; CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLISM; D-DEPENDENT RICKETS; D-DEFICIENCY RICKETS; PARATHYROID-HORMONE; AUTOSOMAL-DOMINANT; ONCOGENIC OSTEOMALACIA C1 [Christov, Marta] Beth Israel Deaconess Med Ctr, Dept Med, Renal Unit, Boston, MA 02215 USA. [Christov, Marta; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Christov, Marta; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Christov, Marta; Jueppner, Harald] Massachusetts Gen Hosp, Dept Med, Pediat Nephrol Unit, Boston, MA 02114 USA. [Christov, Marta; Jueppner, Harald] Massachusetts Gen Hosp, Dept Pediat, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Christov, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM mchristov@partners.org FU National Institutes of Health, National Institute for Diabetes and Digestive and Kidney Diseases [DK-46718, DK-11794, DK-93608] FX supported by grants from the National Institutes of Health, National Institute for Diabetes and Digestive and Kidney Diseases (DK-46718 and DK-11794 (subproject IV) to H.J. and DK-93608 to M.C.). NR 139 TC 9 Z9 9 U1 0 U2 35 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 2013 VL 33 IS 2 BP 143 EP 157 DI 10.1016/j.semnephrol.2012.12.015 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 106SM UT WOS:000316165000006 PM 23465501 ER PT J AU Anderson, CD Biffi, A Nalls, MA Devan, WJ Schwab, K Ayres, AM Valant, V Ross, OA Rost, NS Saxena, R Viswanathan, A Worrall, BB Brott, TG Goldstein, JN Brown, D Broderick, JP Norrving, B Greenberg, SM Silliman, SL Hansen, BM Tirschwell, DL Lindgren, A Slowik, A Schmidt, R Selim, M Roquer, J Montaner, J Singleton, AB Kidwell, CS Woo, D Furie, KL Meschia, JF Rosand, J AF Anderson, Christopher D. Biffi, Alessandro Nalls, Michael A. Devan, William J. Schwab, Kristin Ayres, Alison M. Valant, Valerie Ross, Owen A. Rost, Natalia S. Saxena, Richa Viswanathan, Anand Worrall, Bradford B. Brott, Thomas G. Goldstein, Joshua N. Brown, Devin Broderick, Joseph P. Norrving, Bo Greenberg, Steven M. Silliman, Scott L. Hansen, Bjoern M. Tirschwell, David L. Lindgren, Arne Slowik, Agnieszka Schmidt, Reinhold Selim, Magdy Roquer, Jaume Montaner, Joan Singleton, Andrew B. Kidwell, Chelsea S. Woo, Daniel Furie, Karen L. Meschia, James F. Rosand, Jonathan CA Int Stroke Genetics Consortium TI Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage SO STROKE LA English DT Article DE genes; mitochondria; OXPHOS; stroke ID COMPLEX I; ASSOCIATION; DISEASE; MICROBLEEDS; DYSFUNCTION; PATHWAY AB Background and Purpose-Previous studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods-This association study used a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing gene-set enrichment analysis were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results-IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio [OR], 1.17; P=0.008) and complex I (OR, 1.06; P=0.050). Among IS subtypes, small vessel stroke showed association with OXPHOS (OR, 1.16; P=0.007), complex I (OR, 1.13; P=0.027), and complex IV (OR, 1.14; P=0.018). To further explore this small vessel association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and complex IV (OR, 1.08; P=0.008). Conclusions-This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for small vessel stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. (Stroke. 2013;44:612-619.) C1 [Anderson, Christopher D.; Biffi, Alessandro; Devan, William J.; Valant, Valerie; Rost, Natalia S.; Saxena, Richa; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Devan, William J.; Valant, Valerie; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Devan, William J.; Schwab, Kristin; Ayres, Alison M.; Valant, Valerie; Rost, Natalia S.; Viswanathan, Anand; Goldstein, Joshua N.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Devan, William J.; Valant, Valerie; Rost, Natalia S.; Saxena, Richa; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Nalls, Michael A.; Singleton, Andrew B.] NIA, Dept Neurogenet, Intramural Res Program, Bethesda, MD 20892 USA. [Ross, Owen A.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA. [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Brown, Devin] Univ Michigan Hlth Syst, Stroke Program, Dept Neurol, Ann Arbor, MI USA. [Broderick, Joseph P.; Woo, Daniel] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA. [Norrving, Bo; Hansen, Bjoern M.; Lindgren, Arne] Lund Univ, Dept Clin Sci Lund, Lund, Sweden. [Norrving, Bo; Hansen, Bjoern M.; Lindgren, Arne] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Stroke Ctr, Seattle, WA 98104 USA. [Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Roquer, Jaume] Univ Autonoma Barcelona, Neurovasc Res Unit, Dept Neurol, E-08193 Barcelona, Spain. [Roquer, Jaume] Univ Autonoma Barcelona, Program Inflammat & Cardiovasc Disorders, Inst Municipal Invest Med, Hosp del Mar, E-08193 Barcelona, Spain. [Montaner, Joan] Univ Autonoma Barcelona, Neurovasc Res Lab, E-08193 Barcelona, Spain. [Montaner, Joan] Univ Autonoma Barcelona, Neurovasc Unit, Inst Recerca, Hosp Vall dHebron, E-08193 Barcelona, Spain. [Kidwell, Chelsea S.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. RP Anderson, CD (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CZPN 5820, Boston, MA 02114 USA. EM cdanderson@partners.org RI Ross, Owen/D-7573-2013; Singleton, Andrew/C-3010-2009; Montaner, Joan/D-3063-2015; Goldstein, Joshua/H-8953-2016; IBIS, NEUROVASCULAR/O-1855-2015; OI Brown, Devin/0000-0002-9815-3421; Hansen, Bjorn/0000-0001-8661-9063; Norrving, Bo/0000-0002-8024-5096; Ayres, Alison/0000-0002-5492-1695; Anderson, Christopher/0000-0002-0053-2002 FU American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010 N]; National Institutes of Health (NIH)-National Institute for Neurological Disorders and Stroke (NINDS) [R01 NS059727, U01 NS069208, R01 NS42733, R01 NS39987, U54NS057405, NS36695, NS30678, K23NS042695, 5K23NS059774, R01NS059727, 5R01NS042147]; Keane Genetics Fund; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; US NIH; National Heart, Lung, and Blood Institute STAMPEED genomics research program [R01 HL087676]; National Center for Research Resources [U54 RR020278]; American Brain Foundation; Intramural Research Program of NIH-National Institute on Aging (NIA) [Z01 AG000954-06, Z01 AG000015-50]; Marriott Disease Risk and Regenerative Medicine Initiative Award in Individualized Medicine; Marriott Mitochondrial Fund; American Heart Association, James and Esther King Biomedical Research Program; Florida Department of Health; Myron and Jane Hanley Award in Stroke Research; National Institute on Minority Health and Health Disparities (NIMHD) [U54NS057405]; Greater Cincinnati Foundation Grant (Cincinnati Control Cohort); Keane Stroke Genetics Research Fund; Edward and Maybeth Sonn Research Fund; University of Michigan General Clinical Research Center [M01 RR000042]; Instituto de Salud Carlos III, Spanish Research Networks Red HERACLES FEDER [RD06/009]; Polish Ministry of Education [NN402083934]; Lund University; Region Skane; King Gustaf V's and Queen Victoria's Foundation; Swedish Medical Research Council [K2010-61X-20378-04-3]; Austrian Science Fund [P20545-P05, P13180]; National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Minority Health and Health Disparities [NS U54NS057405] FX Massachusetts General Hospital/MIGen: These studies were funded by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010 N), the National Institutes of Health (NIH)-National Institute for Neurological Disorders and Stroke (NINDS; R01 NS059727, U01 NS069208), The Keane Genetics Fund, and the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke. The MIGen study was funded by the US NIH and National Heart, Lung, and Blood Institute STAMPEED genomics research program (R01 HL087676) and a grant from the National Center for Research Resources. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research resources. C.D.A., A.B., and N.S.R. were supported in part by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research, and C.D.A. was supported by the American Brain Foundation.; Ischemic Stroke Genetics Study/Siblings with Ischemic Stroke Study: These studies were funded by NIH-NINDS (R01 NS42733, R01 NS39987), the Intramural Research Program of NIH-National Institute on Aging (NIA; Z01 AG000954-06), and by the Marriott Disease Risk and Regenerative Medicine Initiative Award in Individualized Medicine and the Marriott Mitochondrial Fund. The inclusion of BLSA samples was supported in part by the Intramural Research Program of NIH-NIA (Z01 AG000015-50). O.A.R. was supported by the American Heart Association, James and Esther King Biomedical Research Program, the Florida Department of Health, and the Myron and Jane Hanley Award in Stroke Research.; International Stroke Genetics Consortium: The Differences in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) project was supported by Award Number U54NS057405 from the NIH-NINDS and National Institute on Minority Health and Health Disparities (NIMHD) (U54NS057405). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health (DECIPHER). The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study was supported by NIH-NINDS (NS36695 and NS30678), and by the Greater Cincinnati Foundation Grant (Cincinnati Control Cohort). The Massachusetts General Hospital Intracerebral Hemorrhage Stroke Genome-Wide Association study was funded by NIH-NINDS (K23NS042695, 5K23NS059774, R01NS059727, and 5R01NS042147), the Keane Stroke Genetics Research Fund, the Edward and Maybeth Sonn Research Fund, by the University of Michigan General Clinical Research Center (M01 RR000042), and by a grant from the National Center for Research Resources. The Hospital del Mar ICH (HM-ICH) study was funded by the Instituto de Salud Carlos III, Spanish Research Networks Red HERACLES (RD06/009) FEDER. The Jagiellonian University Hemorrhagic Stroke Study (JUHSS) was supported by a grant funded by the Polish Ministry of Education (NN402083934). The Lund Stroke Register (LSR) was funded by Lund University, Region Skane, King Gustaf V's and Queen Victoria's Foundation, and the Swedish Medical Research Council (K2010-61X-20378-04-3). Biobank services and genotyping were done at Region Skane Competence Center (RSKC Malmo), Skane University Hospital, Malmo, Sweden. Controls from the Medical University of Graz ICH (MUG-ICH) study were from the Austrian Stroke Prevention Study, which is a population-based study funded by the Austrian Science Fund grant numbers P20545-P05 and P13180; the Medical University of Graz supports the databank of the Austrian Stroke Prevention Study.; This work used samples and clinical data from the National Institutes of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds). This study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (NIH), Bethesda, MD (http://biowulf.nih.gov). The project described was supported in part by a grant from the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Minority Health and Health Disparities (NS U54NS057405). The content is solely the responsibility of the authors and does not necessarily represent the official views of NINDS or NIH. NR 30 TC 14 Z9 15 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2013 VL 44 IS 3 BP 612 EP + DI 10.1161/STROKEAHA.112.672089 PG 49 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 097AW UT WOS:000315447400013 PM 23362085 ER PT J AU Morrow, DA Alberts, MJ Mohr, JP Ameriso, SF Bonaca, MP Goto, S Hankey, GJ Murphy, SA Scirica, BM Braunwald, E AF Morrow, David A. Alberts, Mark J. Mohr, Jay P. Ameriso, Sebastian F. Bonaca, Marc P. Goto, Shinya Hankey, Graeme J. Murphy, Sabina A. Scirica, Benjamin M. Braunwald, Eugene CA Thrombin Receptor Antagonist TI Efficacy and Safety of Vorapaxar in Patients With Prior Ischemic Stroke SO STROKE LA English DT Article DE clinical trial; secondary prevention; stroke; thrombin ID THROMBIN-RECEPTOR ANTAGONIST; ACUTE CORONARY SYNDROMES; SECONDARY PREVENTION; 50 TRIAL; CLOPIDOGREL; ASPIRIN; EVENTS; ATHEROTHROMBOSIS; DIPYRIDAMOLE; OUTPATIENTS AB Background and Purpose-Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the protease-activated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods-We randomly assigned patients with prior atherothrombosis (myocardial infarction, peripheral artery disease, or ischemic stroke) to receive vorapaxar (2.5 mg daily) or placebo added to standard antiplatelet therapy. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 weeks to 12 months. The primary end point was the composite of cardiovascular death, myocardial infarction, or any stroke. Results-The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other/unknown in 18%. In the stroke cohort, cardiovascular death, myocardial infarction, or stroke through 3 years was not reduced with vorapaxar versus placebo (13.0% vs 11.7%; hazard ratio, 1.03; 95% confidence interval, 0.85-1.25), including recurrent ischemic stroke (hazard ratio, 0.99; 95% confidence interval, 0.78-1.25). There were no significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke. Intracranial hemorrhage at 3 years was increased with vorapaxar (2.5% vs 1.0%; hazard ratio, 2.52; 95% confidence interval, 1.46-4.36). Conclusions-In patients with prior ischemic stroke who receive standard antiplatelet therapy, adding vorapaxar increased the risk of intracranial hemorrhage without an improvement in major vascular events, including ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke. Clinical Trial Registration Information-http://www.clinicaltrials.gov. Unique identifier: NCT00526474. (Stroke. 2013; 44:691-698.) C1 [Morrow, David A.; Bonaca, Marc P.; Murphy, Sabina A.; Scirica, Benjamin M.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Alberts, Mark J.] Univ Texas Southwestern, Dept Neurol, Dallas, TX USA. [Mohr, Jay P.] Columbia Univ, Dept Neurol, New York, NY USA. [Ameriso, Sebastian F.] Raul Carrea Inst Neurol Res FLENI, Buenos Aires, DF, Argentina. [Goto, Shinya] Tokai Univ, Sch Med, Div Cardiol, Tokyo 151, Japan. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Merck; Abbott; AstraZeneca; Amgen; Bristol-Myers Squibb; Daiichi Sankyo; Eisai; Eli Lilly; GlaxoSmithKline; Novartis; Johnson Johnson; Boehringer Ingelheim; Sanofi Aventis; Utsuka FX This study was supported by Merck.; Dr Morrow reports that the Thrombolysis in Myocardial Infarction (TIMI) Study Group has received research grants from Abbott, AstraZeneca, Amgen, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Merck, Novartis, and Johnson & Johnson. He reports having served as a consultant for Merck, Boehringer Ingelheim, Gilead, Genentech, and Servier. Dr Alberts has received grants from Merck, been on the speaker's bureau for Sanofi Aventis, and is a paid consultant for Sanofi Aventis, Merck, and Pozen. Dr Mohr has received consulting fees from Merck. Dr Ameriso has received grants from Merck and has served on the speaker's bureau for Bayer, Bristol-Myers Squibb, and Boehringer Ingelheim. Dr Bonaca is a member of the TIMI Study Group. Dr Goto has received grants from Boehringer Ingelheim, Daiichi Sankyo, Sanofi Aventis, and Utsuka. He has received honoraria from AstraZeneca and Sanofi Aventis, and been a consultant to Bayer and Bristol-Myers Squibb. Dr Hankey has received honoraria for serving on the executive committee of clinical trials (Boehringer Ingelheim, Johnson & Johnson, Merck, and Sanofi Aventis). He has received honoraria from Bayer, Boehringer Ingelheim, and Pfizer Australia for speaking at sponsored symposia and consulting. S. A. Murphy is a member of the TIMI Study Group. She has been a consultant for Eli Lilly and Amarin Pharmaceuticals. Dr Scirica is a member of the TIMI Study Group. He has been a consultant for Lexicon, Arena, Gilead, and Eisai. Dr Braunwald is a member of the TIMI Study Group. He has served as a consultant for Merck (no compensation), Amorcyte, Daiichi Sankyo, Medicines Co, Ikaria, and CVRx (no compensation). NR 16 TC 43 Z9 44 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2013 VL 44 IS 3 BP 691 EP + DI 10.1161/STROKEAHA.111.000433 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 097AW UT WOS:000315447400026 PM 23396280 ER PT J AU Fan, X Lo, EH Wang, XY AF Fan, Xiang Lo, Eng H. Wang, Xiaoying TI Effects of Minocycline Plus Tissue Plasminogen Activator Combination Therapy After Focal Embolic Stroke in Type 1 Diabetic Rats SO STROKE LA English DT Article DE combination therapy; diabetes mellitus; embolic stroke; hyperglycemia; minocycline; tissue plasminogen activator ID ACUTE ISCHEMIC-STROKE; CEREBRAL-ISCHEMIA; HEMORRHAGIC COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; ADMISSION HYPERGLYCEMIA; BRAIN INFLAMMATION; THROMBOLYSIS; REPERFUSION; MODEL; PREDICTS AB Background and Purpose-Poststroke hyperglycemia is associated with resistance to tissue plasminogen activator (tPA) reperfusion, higher risk of intracerebral hemorrhage, and worse neurological outcomes. In this study, we asked whether minocycline combined with intravenous tPA may ameliorate inflammation and brain injury after focal embolic stroke in type 1 diabetic rats. Methods-Type 1 diabetic rats were subjected to a focal embolic stroke. Three treatment groups were used: (1) saline at 1.5 hours after stroke; (2) tPA alone at 1.5 hours after stroke; (3) combined minocycline (intravenously) at 1 hour plus tPA at 1.5 hours, and second treatment of minocycline (intraperitoneally) at 12 hours after stroke. Acute brain tissue damages were assessed at 24 hours after stroke. Inflammatory biomarkers interleukin-1 beta and matrix metalloproteinases 2 and 9 were examined in plasma. Neutrophil infiltration, microglia activation, matrix metalloproteinase activation, and degradation of the tight junction protein claudin-5 were examined in the brain. Results-Compared with saline or tPA alone treatments, minocycline plus tPA combination therapy significantly reduced brain infarction, intracerebral hemorrhage, and hemispheric swelling at 24 hours after stroke. The combination also significantly suppressed the elevated plasma levels of matrix metalloproteinase-9 and interleukin-1 beta up to 24 hours after stroke. At 16 hours after stroke, neutrophil infiltration, microglia activation, matrix metalloproteinase-9, and tight junction protein claudin-5 degradation in the peri-infarct brain tissues were also significantly attenuated by the combination therapy. Conclusions-Combination therapy with minocycline plus tPA may be beneficial in ameliorating inflammation and reducing infarction, brain swelling, and hemorrhage after ischemic stroke with diabetes mellitus/hyperglycemia. (Stroke. 2013;44:745-752.) C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuroprotect Res Lab,Neurosci Program, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neuroprotect Res Lab,Neurosci Program, Boston, MA 02129 USA. RP Wang, XY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuroprotect Res Lab, 149 13th St,Room 2411A, Boston, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU National Institutes of Health [R01-NS065998, UO1-NS072324] FX This work was supported, in part, by the National Institutes of Health grants R01-NS065998 and UO1-NS072324 (to X. Wang). NR 38 TC 24 Z9 24 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2013 VL 44 IS 3 BP 745 EP + DI 10.1161/STROKEAHA.111.000309 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 097AW UT WOS:000315447400034 PM 23422086 ER PT J AU Linos, D Economopoulos, KP Kiriakopoulos, A Linos, E Petralias, A AF Linos, Dimitrios Economopoulos, Konstantinos P. Kiriakopoulos, Andreas Linos, Eleni Petralias, Athanassios TI Scar perceptions after thyroid and parathyroid surgery: Comparison of minimal and conventional approaches SO SURGERY LA English DT Article ID VIDEO-ASSISTED THYROIDECTOMY; ROBOTIC THYROIDECTOMY; ASSESSMENT QUESTIONNAIRE; LOBECTOMY; OUTCOMES; ACCESS AB Background. An incision less than 3 cm in length in the neck is the main feature that discriminates the minimally invasive thyroidectomy and parathyroidectomy from traditional procedures. Smaller neck scars are assumed to yield better patient satisfaction, although no established data support this. In this analysis, we evaluated the satisfaction of patients who had undergone both procedures, while examining the effects of sociodemographic and surgical characteristics. Methods. We analyzed data from 691 patients who underwent a thyroidectomy or parathyroidectomy between January 2000 and March 2010. We assessed the satisfaction of patients who underwent conventional compared to minimally invasive procedures, using the validated Patient Scar Assessment Questionnaire (PSAQ). We included both the appearance and the consciousness subscales. Results. Overall, patients were satisfied with their neck scars, as indicated by the low scores in appearance (13.3; range, 9 to 31) and consciousness (8.5; range, 6 to 24) subscales. The degree of satisfaction, improved with increased time since surgery (P<.001). Patient satisfaction was similar regardless of the procedure used, implying that smaller scars do not provide better patient satisfaction. Most patients (81.2%) reported that they would not have preferred a transaxillary procedure over the procedure they received. Conclusion. A smaller incision in the neck was not associated with better patient satisfaction. New surgical approaches aimed at maximizing cosmesis while minimizing scar size should be evaluated for cost-effectiveness and clinical outcomes, as well as patient-satisfaction, before becoming the standard of care. (Surgery 2013;153:400-7.) C1 [Linos, Dimitrios] Athens Med Sch, Athens, Greece. [Linos, Dimitrios; Kiriakopoulos, Andreas] Hygeia Hosp, Dept Surg, Athens, Greece. [Linos, Dimitrios; Economopoulos, Konstantinos P.; Petralias, Athanassios] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Linos, Eleni] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Petralias, Athanassios] Athens Univ Econ & Business, Dept Stat, Athens, Greece. RP Linos, D (reprint author), Fragoklisias 7, Athens 15125, Greece. EM dlinos@hms.harvard.edu RI Linos, Eleni/C-4392-2014; OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700; Economopoulos, Konstantinos/0000-0003-4856-0405 NR 33 TC 15 Z9 16 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2013 VL 153 IS 3 BP 400 EP 407 DI 10.1016/j.surg.2012.08.008 PG 8 WC Surgery SC Surgery GA 101AQ UT WOS:000315748000016 PM 22980435 ER PT J AU Lawson, EH Ko, CY Louie, R Han, L Rapp, M Zingmond, DS AF Lawson, Elise H. Ko, Clifford Y. Louie, Rachel Han, Lein Rapp, Michael Zingmond, David S. TI Linkage of a clinical surgical registry with Medicare inpatient claims data using indirect identifiers SO SURGERY LA English DT Article ID SURGERY; LINKING; NSQIP AB Background. A variety of data sources are available for measuring the quality of health care. Linking records from different sources can create unique and powerful databases that can be used to evaluate clinically relevant questions and direct health care policy. The objective of this study was to develop and validate a deterministic linkage algorithm that uses indirect patient identifiers to reliably match records from a surgical clinical registry with Medicare inpatient claims data. Methods. Patient records from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), years 2005-2008, were linked to claims data in the Medicare Provider Analysis and Review file (MedPAR) by the use of a deterministic linkage algorithm and the following indirect patient identifiers: hospital, age, sex, diagnosis, procedure and dates of admission, discharge, and procedure. We validated the linkage procedure by systematically reviewing subsets of matched and unmatched records and by determining agreement on patient-level coding of inpatient mortality. Results. Of the 150,454 records in ACS-NSQIP eligible for matching, 80.5% were linked to a MedPAR record. This percentage is within the expected match range given the estimated percentage of ACS-NSQIP patients likely to be Medicare beneficiaries. Systematic checks revealed no evidence of bias in the linkage procedure and there was excellent agreement on patient-level coding of mortality (kappa 0.969). The final linked database contained 121,070 patient records from 217 hospitals. Conclusion. This study demonstrates the feasibility and validity of a method for linking 2 data sources without direct personal identifiers. As clinical registries and other data sources continue to proliferate, linkage algorithms such as described here will be critical for quality measurement purposes. (Surgery 2013;153:423-30.) C1 [Lawson, Elise H.; Ko, Clifford Y.; Louie, Rachel; Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lawson, Elise H.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Lawson, Elise H.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Han, Lein; Rapp, Michael] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave 72-215 CHS, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu FU Centers for Medicare & Medicaid Services (CMS); VA Health Services Research and Development program [RWJ 65-020]; American College of Surgeons through the Robert Wood Johnson Foundation Clinical Scholars Program FX Supported by a contract from the Centers for Medicare & Medicaid Services (CMS). In addition, Dr Lawson's time was supported by the VA Health Services Research and Development program (RWJ 65-020) and the American College of Surgeons through the Robert Wood Johnson Foundation Clinical Scholars Program. Dr Ko is an employee of the American College. of Surgeons. Dr Han and Dr Rapp are employees of CMS. NR 5 TC 24 Z9 24 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2013 VL 153 IS 3 BP 423 EP 430 DI 10.1016/j.surg.2012.08.065 PG 8 WC Surgery SC Surgery GA 101AQ UT WOS:000315748000019 PM 23122901 ER PT J AU Daniels, GH AF Daniels, Gilbert H. TI Radioactive Iodine: A Slice of History SO THYROID LA English DT Editorial Material ID GRAVES-DISEASE; HYPERTHYROIDISM; THYROTOXICOSIS; RADIOIODINE; THERAPY; HYPERPARATHYROIDISM; HYPOTHYROIDISM; METABOLISM; CHERNOBYL; SURGERY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Med,Thyroid Unit, Boston, MA 02114 USA. RP Daniels, GH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Med,Thyroid Unit, Boston, MA 02114 USA. EM gdaniels@partners.org NR 31 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 1050-7256 J9 THYROID JI Thyroid PD MAR PY 2013 VL 23 IS 3 BP 253 EP 258 DI 10.1089/thy.2011.0333 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 103XD UT WOS:000315951900001 PM 23121056 ER PT J AU Vivero, M Kraft, S Barletta, JA AF Vivero, Marina Kraft, Stefan Barletta, Justine A. TI Risk Stratification of Follicular Variant of Papillary Thyroid Carcinoma SO THYROID LA English DT Article ID INCREASING INCIDENCE; GENETIC ALTERATIONS; GROWTH-PATTERN; UNITED-STATES; CANCER; FEATURES; SURVIVAL; DIAGNOSIS; ENTITY AB Background: Recent studies have described an encapsulated and an infiltrative form of follicular variant of papillary thyroid carcinoma (FVPTC). While encapsulated tumors have been reported to have virtually no metastatic potential or recurrence risk if angioinvasion and capsular penetration are absent, infiltrative tumors have been found to have a significant metastatic potential and a risk of recurrence. In our experience, a substantial number of FVPTCs are neither fully encapsulated nor infiltrative, but instead are partially-encapsulated (PE) or well-circumscribed (WC). Thus, the aim of this study was to investigate the metastatic potential and recurrence risk of PE/WC FVPTCs in comparison with that of encapsulated and infiltrative tumors. Methods: We studied 77 FVPTCs resected between 2000 and 2002 and characterized the tumors as encapsulated, PE/WC, or infiltrative. Histologic assessment was then correlated with lymph node status and clinical outcome. Results: In our cohort, 27 (35%) tumors were encapsulated, 35 (45%) were PE/WC, and 15 (19%) were infiltrative. Lymph node status was similar between PE/WC and encapsulated tumors, but was significantly different between encapsulated and infiltrative groups (p < 0.001), and PE/WC and infiltrative groups (p < 0.001). Lymph node metastases were absent in all 15 cases of encapsulated tumors and all 9 cases of PE/WC tumors with sampled lymph nodes, but were present in 7 of 9 (78%) cases of infiltrative tumors with sampled lymph nodes. For patients with available clinical follow-up (66 cases, 86%), the median follow-up time was 111 months. No patients with encapsulated tumors recurred, one (3%) patient with a PE/WC tumor had recurrent/residual disease, and two (15%) patients with infiltrative tumors had recurrent/residual disease. The one patient with a PE/WC tumor who had recurrent/residual disease had a tumor bed recurrence 7 years after initial resection. Significantly, this was the only patient in the PE/WC group that had a positive resection margin. Conclusions: Our results demonstrate that PE/WC FVPTCs have a very low metastatic potential/recurrence risk, indicating that they should be distinguished from more aggressive infiltrative FVPTCs. C1 [Vivero, Marina; Barletta, Justine A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kraft, Stefan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kraft, Stefan] Harvard Univ, Sch Med, Boston, MA USA. RP Barletta, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jbarletta@partners.org FU Eleanor and Miles Shore Fellowship for Scholars in Medicine, Harvard Medical School FX This work was supported by the Eleanor and Miles Shore Fellowship for Scholars in Medicine, Harvard Medical School. NR 29 TC 47 Z9 48 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAR PY 2013 VL 23 IS 3 BP 273 EP 279 DI 10.1089/thy.2012.0369 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 103XD UT WOS:000315951900005 PM 23025507 ER PT J AU Stickrath, C Aagaard, E Anderson, M AF Stickrath, Chad Aagaard, Eva Anderson, Mel TI MiPLAN: A Learner-Centered Model for Bedside Teaching in Today's Academic Medical Centers SO ACADEMIC MEDICINE LA English DT Article ID DUTY-HOUR REGULATIONS; INTERNAL-MEDICINE; CASE PRESENTATIONS; ATTENDING ROUNDS; EXAMINATION ROOM; EDUCATION; STUDENTS; STRATEGIES; RESIDENT; FACULTY AB Clinician educators and medical trainees face intense pressure to complete numerous patient care and teaching activities in a limited amount of time. To address the need for effective and efficient teaching methods for use in the inpatient setting, the authors used constructivist learning theory, the principles of adult learning, and their expertise as clinician educators to develop the MiPLAN model for bedside teaching. This three-part model is designed to enable clinical teachers to simultaneously provide care to patients while assessing learners, determining high-yield teaching topics, and providing feedback to learners. The "M" refers to a preparatory meeting between teacher and learners before engaging in patient care or educational activities. During this meeting, team members should become acquainted and the teacher should set goals and clarify expectations. The "i" refers to five behaviors for the teacher to adopt during learners' bedside presentations: introduction, in the moment, inspection, interruptions, and independent thought. "PLAN" is an algorithm to establish priorities for teaching subsequent to a learner's presentation: patient care, learners' questions, attending's agenda, and next steps. The authors suggest that the MiPLAN model can help clinical teachers gain more confidence in their ability to teach at the bedside and increase the frequency and quality of bedside teaching. They propose further research to assess the generalizability of this model to other institutions, settings, and specialties and to evaluate educational and patient outcomes. C1 [Stickrath, Chad; Aagaard, Eva; Anderson, Mel] Univ Colorado, Sch Med, Aurora, CO USA. [Stickrath, Chad; Anderson, Mel] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Stickrath, C (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St 111, Denver, CO 80220 USA. EM Chad.Stickrath@va.gov NR 38 TC 10 Z9 10 U1 1 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAR PY 2013 VL 88 IS 3 BP 322 EP 327 DI 10.1097/ACM.0b013e318280d8f7 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 098CJ UT WOS:000315522600016 PM 23348088 ER PT J AU Cheriyan, T Ready, JE Brick, GW Martin, SD Martin, TL Schmid, TM Padera, RF Spector, M AF Cheriyan, Thomas Ready, John E. Brick, Gregory W. Martin, Scott D. Martin, Tamara L. Schmid, Thomas M. Padera, Robert F. Spector, Myron TI Lubricin and smooth muscle alpha-actin-containing myofibroblasts in the pseudomembranes around loose hip and knee prostheses SO ACTA BIOMATERIALIA LA English DT Article DE Prosthesis; Loosening; Pseudomembrane; Lubricin; Smooth muscle actin ID SUPERFICIAL ZONE PROTEIN; EXPRESSION; MEMBRANE; BONE; ARTHROPLASTY; INTERFACE; TENDON; TISSUE AB The objective was to evaluate the presence and distribution of the lubricating and anti-adhesion glycoprotein lubricin and cells containing the contractile isoform smooth muscle alpha-actin (SMA) in pseudo-membranes around loose hip prostheses. Periprosthetic tissue was obtained at revision arthroplasty of eight aseptic, loose hip implants, and for comparison three loose knee prostheses. Immunohistochemical analysis was performed in 3 zones: zone 1, within 300 mu m of the edge of the implant-tissue interface; zone 2, between zones 1 and 3; zone 3, within 300 mu m of the resected/trimmed edge. The presence of lubricin was extensive in all samples: (1) as a discrete layer at the implant-tissue interface; (2) within the extracellular matrix (ECM); (3) intracellularly. There was significantly more high grade (>50%) lubricin surface staining at the implant-tissue interface compared with the resected edge. While there was also a significant effect of location of high grade ECM lubricin staining, there was no significant effect of implant type (i.e. hip versus knee). All but two hip pseudomembrane samples showed the presence of many SMA-containing cells. There was a significant effect of location on the number of SMA-expressing cells, but not of implant type. These findings might explain why the management of loose prosthesis is so challenging. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Cheriyan, Thomas; Martin, Tamara L.; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Cheriyan, Thomas; Ready, John E.; Brick, Gregory W.; Martin, Scott D.; Martin, Tamara L.; Padera, Robert F.; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Cheriyan, Thomas] NYU, Hosp Joint Dis, Dept Orthopaed Surg, New York, NY 10003 USA. [Schmid, Thomas M.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Department of Veterans Affairs, Veterans Health Administration Research and Development Service FX This work was supported in part by the Department of Veterans Affairs, Veterans Health Administration Research and Development Service. M.S. is a Veterans Administration Research Career Scientist. NR 16 TC 1 Z9 1 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD MAR PY 2013 VL 9 IS 3 BP 5751 EP 5758 DI 10.1016/j.actbio.2012.11.010 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 098GH UT WOS:000315536000035 PM 23174700 ER PT J AU Durazzo, TC Mon, A Gazdzinski, S Meyerhoff, DJ AF Durazzo, Timothy C. Mon, Anderson Gazdzinski, Stefan Meyerhoff, Dieter J. TI Chronic cigarette smoking in alcohol dependence: associations with cortical thickness and N-acetylaspartate levels in the extended brain reward system SO ADDICTION BIOLOGY LA English DT Review DE Alcohol dependence; brain reward system; cigarette smoking; cortical thickness; N-acetylaspartate; nicotine ID MAGNETIC-RESONANCE-SPECTROSCOPY; FRONTAL-SUBCORTICAL CIRCUITS; NATIONAL EPIDEMIOLOGIC SURVEY; ANTERIOR CINGULATE CORTEX; PROTON MR SPECTROSCOPY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; SHORT-TERM RECOVERY; DSM-IV ALCOHOL; ORBITOFRONTAL CORTEX AB Chronic smoking in alcohol dependence is associated with abnormalities in brain morphology and metabolite levels in large lobar regions (e.g. frontal lobe). Here, we evaluated if these abnormalities are specifically apparent in several cortical and select subcortical components of the extended brain reward system (BRS), a network that is critically involved in the development and maintenance of all forms of addictive disorders. We studied 33 non-smoking and 43 smoking alcohol-dependent individuals (ALC) with 1 week of abstinence and 42 non-smoking Controls. At 1.5 Tesla, we obtained regional measures of cortical thickness and N-acetylaspartate (NAA; a surrogate marker of neuronal integrity) concentration in major components of the BRS as well as the corresponding measures throughout the cortex. Smoking ALC and non-smoking ALC demonstrated decreased thickness compared with Controls in the dorsolateral prefrontal cortex (DLPFC), insula, orbitofrontal cortex (OFC), the total BRS, total frontal cortex and global cortex. Smoking ALC had significantly decreased thickness compared to non-smoking ALC in the ACC, insula, the total BRS and total frontal cortex. Smoking ALC had also lower NAA concentrations than both non-smoking ALC and Controls in the DLPFC, insula, superior corona radiata and the total BRS. Alcohol consumption and common medical and psychiatric co-morbidities did not mediate differences between smoking and non-smoking ALC. This dual modality magnetic resonance (MR) study indicated that chronic smoking in ALC was associated with significant cortical thinning and NAA abnormalities in anterior brain regions that are implicated in the development and maintenance of addictive disorders. C1 [Durazzo, Timothy C.; Mon, Anderson; Gazdzinski, Stefan; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Mon, Anderson; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU National Institutes of Health [AA10788, DA24136] FX This work was supported by the National Institutes of Health [AA10788 to D.J.M.; DA24136 to T. C. D.] and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. The authors have no disclosures or conflicts of interest to report. We thank Mary Rebecca Young, Bill Clift, and Drs. Peter Banys and Ellen Herbst of the Veterans Administration Substance Abuse Day Hospital, which routinely offers smoking cessation with substance abuse treatment, and Dr. David Pating, Karen Moise and their colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 112 TC 18 Z9 18 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD MAR PY 2013 VL 18 IS 2 BP 379 EP 391 DI 10.1111/j.1369-1600.2011.00407.x PG 13 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 097VB UT WOS:000315500500017 PM 22070867 ER PT J AU McGinnis, KA Justice, AC Kraemer, KL Saitz, R Bryant, KJ Fiellin, DA AF McGinnis, Kathleen A. Justice, Amy C. Kraemer, Kevin L. Saitz, Richard Bryant, Kendall J. Fiellin, David A. TI Comparing Alcohol Screening Measures Among HIV-Infected and -Uninfected Men SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE AUDIT; HIV; Veterans; Alcohol-Related Disorders; Mass Screening ID IDENTIFICATION TEST AUDIT; USE DISORDERS; PRIMARY-CARE; CONSUMPTION QUESTIONS; DISEASE PROGRESSION; FOLLOW-UP; DRINKING; RELIABILITY; DRINKERS; RISK AB Background Brief measures of unhealthy alcohol use have not been well validated among people with HIV. We compared the Alcohol Use Disorders Identification Test (AUDIT) to reference standards for unhealthy alcohol use based on 30-day Timeline Follow Back (TLFB) and Composite International Diagnostic InterviewSubstance Abuse Module (CIDI-SAM), among 837 male HIV-infected and -uninfected patients in the Veterans Aging Cohort Study. Methods Three reference standards were (i) Risky drinkingbased on TLFB >14 drinks over 7 consecutive days or >4 drinks on 1day; (ii) Alcohol dependencebased on a CIDI-SAM diagnosis; and (iii) Unhealthy alcohol userisky drinking or a CIDI-SAM diagnosis of abuse or dependence. Various cutoffs for the AUDIT, AUDIT-C, and heavy episodic drinking were compared with the reference standards. Results Mean age of patients was 52years, 53% (444) were HIV-infected, and 53% (444) were African American. Among HIV-infected and -uninfected patients, the prevalence of risky drinking (14 vs. 12%, respectively), alcohol dependence (8 vs. 7%), and unhealthy alcohol use (22 vs. 20%) was similar. For risky drinking and alcohol dependence, multiple cutoffs of AUDIT, AUDIT-C, and heavy episodic drinking provided good sensitivity (80%) and specificity (90%). For unhealthy alcohol use, few cutoffs provided sensitivity 80%; however, many cutoffs provided good specificity. For all 3 alcohol screening measures, sensitivity improved when heavy episodic drinking was included with the cutoff. Sensitivity of measures for risky drinking and unhealthy alcohol use was lower in HIV-infected than in uninfected patients. Conclusions For identifying risky drinking, alcohol dependence, and unhealthy alcohol use, AUDIT-C performs as well as AUDIT and similarly in HIV-infected and -uninfected patients. Cutoffs should be based on the importance of specific operating characteristics for the intended research or clinical use. Incorporating heavy episodic drinking increased sensitivity for detecting alcohol dependence and unhealthy alcohol use. C1 [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Div Gen Internal Med, New Haven, CT USA. [Justice, Amy C.; Fiellin, David A.] West Haven VA Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, West Haven, CT USA. [Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [Kraemer, Kevin L.] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA USA. [Saitz, Richard] Boston Med Ctr, Dept Med, Clin Addict Res & Educ CARE Unit, Gen Internal Med Sect, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. [Saitz, Richard] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Bryant, Kendall J.] NIAAA, Bethesda, MD USA. RP McGinnis, KA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM kathleen.mcginnis3@va.gov OI Fiellin, David/0000-0002-4006-010X; /0000-0002-2535-1427 FU National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566] FX The Veterans Aging Cohort Study is funded by the National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566). NR 34 TC 15 Z9 15 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2013 VL 37 IS 3 BP 435 EP 442 DI 10.1111/j.1530-0277.2012.01937.x PG 8 WC Substance Abuse SC Substance Abuse GA 097VC UT WOS:000315500600009 PM 23050632 ER PT J AU Lim, S Kim, MJ Choi, SH Shin, CS Park, KS Jang, HC Billings, LK Meigs, JB AF Lim, Soo Kim, Min Joo Choi, Sung Hee Shin, Chan Soo Park, Kyong Soo Jang, Hak Chul Billings, Liana K. Meigs, James B. TI Association of vitamin D deficiency with incidence of type 2 diabetes in high-risk Asian subjects SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID SERUM 25-HYDROXYVITAMIN D; BETA-CELL DYSFUNCTION; GLUCOSE-TOLERANCE; INSULIN SENSITIVITY; OLDER-ADULTS; PANCREATIC-SECRETION; PARATHYROID-HORMONE; HYPOVITAMINOSIS-D; D INADEQUACY; COHORT AB Background: Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes (T2D) risk. However, prospective studies investigating the relation between vitamin D inadequacy and incidence of T2D incorporating obesity and dynamic measures of insulin resistance (IR) and pancreatic beta cell function are limited. Objective: We tested the hypothesis that baseline 25(OH)D is associated with the incidence of T2D in high-risk subjects for up to 5 y of follow-up, independently of obesity, baseline IR. and beta cell function. Design: We recruited 1080 nondiabetic Korean subjects [mean +/- SD age: 49.5 +/- 11.4 y] based on the presence of one or more risk factors for T2D, including obesity, hypertension, dyslipidemia, and/or family history of T2D. We measured anthropometric and biochemical indicators, HOMA2-IR, and the insulinogenic index (IGI; calculated as change in insulin at 30 min/change in glucose at 30 min) from a 75-g oral-glucose-tolerance test. Results: Of the participants, 10.5% had a serum 25(OH)D deficiency (<10 ng/mL), 51.6% had an insufficiency (10.0-19.9 ng/mL), and 38.0% had a sufficiency (>= 20 ng/mL), and the incidence of T2D at 32.3 +/- 15.6 mo (+/- SD) declined accordingly: 15.9%, 10.2%, and 5.4%, respectively (P < 0.001). After adjustment for age, sex, blood pressure, lifestyles, family history, season, parathyroid hormone, and high-sensitivity C-reactive protein, the participants with 25(OH)D deficiency had an increased risk of T2D independently of BMI, HOMA2-IR, and IGI; the HRs were 2.06 (95% CI: 1.22, 3.49) for 25(OH)D 10-19.9 ng/mL compared with >= 20 ng/mL and 3.23 (95% CI: 1.66, 6.30) for 25(OH)D <10 ng/mL compared with >= 20 ng/mL. Conclusion: The current prospective study suggests that vitamin D metabolism may play a role in T2D pathogenesis independently of known risk factors. This trial was registered at clinicaltrials.gov as NCT01508481. Am J Curt Nutr 2013;97:524-30. C1 [Lim, Soo; Kim, Min Joo; Choi, Sung Hee; Jang, Hak Chul] Seoul Natl Univ, Coll Med, Songnam 463707, South Korea. [Lim, Soo; Kim, Min Joo; Choi, Sung Hee; Jang, Hak Chul] Seoul Natl Univ, Bundang Hosp, Songnam 463707, South Korea. [Shin, Chan Soo; Park, Kyong Soo] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Billings, Liana K.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Boston, MA 02114 USA. [Lim, Soo; Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, HC (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 300 Gumi Dong, Songnam 463707, South Korea. EM janghak@snu.ac.kr RI Park, Kyong Soo/C-2265-2008; OI Park, Kyong Soo/0000-0003-3597-342X; CHOI, SUNG HEE/0000-0003-0740-8116 FU National Research Foundation; Korean government [2006-2005410]; Seoul National University Bundang Hospital; Seoul Research & Business Development program, Republic of Korea [10526]; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [K24 DK080140]; Endocrine Society's Lilly Endocrine Scholar's Award; NIH Loan Repayment Award; NIDDK [1 L30 DK089944-01]; Doris Duke Charitable Foundation FX Supported by the National Research Foundation grant funded by the Korean government (2006-2005410), Seoul National University Bundang Hospital, and Seoul Research & Business Development program, Republic of Korea (10526). JBM was supported by the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) K24 DK080140. LKB was supported by the Endocrine Society's Lilly Endocrine Scholar's Award, NIH Loan Repayment Award, NIDDK 1 L30 DK089944-01, and a Distinguished Clinical Scientist Award to David Altshuler from the Doris Duke Charitable Foundation. NR 49 TC 36 Z9 40 U1 1 U2 18 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2013 VL 97 IS 3 BP 524 EP 530 DI 10.3945/ajcn.112.048496 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 096UV UT WOS:000315431000011 PM 23364011 ER PT J AU Sadrzadeh, H Hasserjian, R Fathi, AT AF Sadrzadeh, Hossein Hasserjian, Robert Fathi, Amir T. TI Pure erythroid leukemia evolving from a therapy-related myelodysplastic syndrome secondary to treatment for chronic lymphocytic leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID ERYTHROLEUKEMIA C1 [Sadrzadeh, Hossein; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol Oncol, Boston, MA 02215 USA. [Hasserjian, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Fathi, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol Oncol, Boston, MA 02215 USA. EM afathi@partners.org NR 4 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2013 VL 88 IS 3 BP 240 EP 241 DI 10.1002/ajh.23224 PG 2 WC Hematology SC Hematology GA 096PB UT WOS:000315415600015 PM 22565525 ER PT J AU Plotkin, SR Blakeley, JO Evans, DG Hanemann, CO Hulsebos, TJM Hunter-Schaedle, K Kalpana, GV Korf, B Messiaen, L Papi, L Ratner, N Sherman, LS Smith, MJ Stemmer-Rachamimov, AO Vitte, J Giovannini, M AF Plotkin, Scott R. Blakeley, Jaishri O. Evans, D. Gareth Hanemann, C. Oliver Hulsebos, Theo J. M. Hunter-Schaedle, Kim Kalpana, Ganjam V. Korf, Bruce Messiaen, Ludwine Papi, Laura Ratner, Nancy Sherman, Larry S. Smith, Miriam J. Stemmer-Rachamimov, Anat O. Vitte, Jeremie Giovannini, Marco TI Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Review DE neurofibromatoses; schwannoma; rhabdoid tumor ID CHROMATIN-REMODELING COMPLEX; TUMOR-SUPPRESSOR GENE; MALIGNANT RHABDOID TUMORS; GERMLINE SMARCB1 MUTATION; AURORA KINASE INHIBITORS; TARGETING CYCLIN D1; NUCLEAR-PROTEIN 2; SWI-SNF COMPLEX; FAMILIAL SCHWANNOMATOSIS; SPORADIC SCHWANNOMATOSIS AB Schwannomatosis is the third major form of neurofibromatosis and is characterized by the development of multiple schwannomas in the absence of bilateral vestibular schwannomas. The 2011 Schwannomatosis Update was organized by the Children's Tumor Foundation (www.ctf.org) and held in Los Angeles, CA, from June 58, 2011. This article summarizes the highlights presented at the Conference and represents the state-of-the-field in 2011. Genetic studies indicate that constitutional mutations in the SMARCB1 tumor suppressor gene occur in 4050% of familial cases and in 810% of sporadic cases of schwannomatosis. Tumorigenesis is thought to occur through a four-hit, three-step model, beginning with a germline mutation in SMARCB1 (hit 1), followed by loss of a portion of chromosome 22 that contains the second SMARCB1 allele and one NF2 allele (hits 2 and 3), followed by mutation of the remaining wild-type NF2 allele (hit 4). Insights from research on HIV and pediatric rhabdoid tumors have shed light on potential molecular pathways that are dysregulated in schwannomatosis-related schwannomas. Mouse models of schwannomatosis have been developed and promise to further expand our understanding of tumorigenesis and the tumor microenvironment. Clinical reports have described the occurrence of intracranial meningiomas in schwannomatosis patients and in families with germline SMARCB1 mutations. The authors propose updated diagnostic criteria to incorporate new clinical and genetic findings since 2005. In the next 5 years, the authors expect that advances in basic research in the pathogenesis of schwannomatosis will lead toward clinical investigations of potential drug therapies. (c) 2013 Wiley Periodicals, Inc. C1 [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Blakeley, Jaishri O.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Evans, D. Gareth; Smith, Miriam J.] Univ Manchester, St Marys Hosp, Manchester Acad Hlth Sci Ctr MAHSC, Dept Med Genet, Manchester M13 9PL, Lancs, England. [Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Med, Plymouth PL4 8AA, Devon, England. [Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Dent, Plymouth PL4 8AA, Devon, England. [Hulsebos, Theo J. M.] Univ Amsterdam, Acad Med Ctr, Dept Genome Anal, NL-1105 AZ Amsterdam, Netherlands. [Hunter-Schaedle, Kim] Childrens Tumor Fdn, New York, NY USA. [Kalpana, Ganjam V.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Kalpana, Ganjam V.] Albert Einstein Coll Med, Ctr Canc, Bronx, NY 10467 USA. [Korf, Bruce; Messiaen, Ludwine] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Papi, Laura] Univ Florence, Dept Clin Physiopathol, Med Genet Unit, Florence, Italy. [Ratner, Nancy] Childrens Hosp, Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Sherman, Larry S.] Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Sherman, Larry S.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Beaverton, OR USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Vitte, Jeremie; Giovannini, Marco] House Ear Res Inst, Los Angeles, CA 90034 USA. RP Plotkin, SR (reprint author), Yawkey 9E Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org RI Smith, Miriam/J-4001-2015; Vitte, Jeremie/B-9874-2017; OI Smith, Miriam/0000-0002-3184-0817; Vitte, Jeremie/0000-0002-2567-7988; Papi, Laura/0000-0003-4552-9517; Hanemann, Clemens Oliver/0000-0002-1951-1025; Evans, Gareth/0000-0002-8482-5784 FU NCI NIH HHS [P30 CA006973] NR 122 TC 50 Z9 53 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR PY 2013 VL 161A IS 3 BP 405 EP 416 DI 10.1002/ajmg.a.35760 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 095NQ UT WOS:000315341700002 PM 23401320 ER PT J AU Skotko, BG Davidson, EJ Weintraub, GS AF Skotko, Brian G. Davidson, Emily Jean Weintraub, Gil S. TI Contributions of a specialty clinic for children and adolescents with Down syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Down syndrome; ambulatory care; clinical practice; trisomy 21 ID OBSTRUCTIVE SLEEP-APNEA; AUTISM SPECTRUM DISORDERS; HEALTH SUPERVISION; CELIAC-DISEASE; CARE; PREVALENCE; GUIDELINES; SEVERITY AB We investigated what added value, if any, a Down syndrome specialty clinic brings to the healthcare needs of children and adolescents with Down syndrome. For this quality improvement study, we performed a retrospective chart review of 105 new patients with Down syndrome, ages 3 and older, seen during the inaugural year of our specialty clinic. We asked how many of our patients were already up-to-date on the healthcare screenings recommended for people with Down syndrome. We further analyzed what tests we ordered, which referrals we suggested, and, ultimately, what new diagnoses of co-occurring medical conditions were made. Only 9.8% of our patients were current on all of the recommended Down syndrome healthcare screenings. Parents came to clinic with a variety of concerns, and after laboratory tests, radiologic studies, and subspecialty referrals, we made many new diagnoses of gastrointestinal conditions (e.g., constipation and celiac disease), seasonal allergies, dermatologic conditions (e.g., xerosis), behavioral diagnoses (e.g., autism spectrum disorder and disruptive behavior not otherwise specified), and clarifications of neurologic conditions. A Down syndrome specialty clinic can identify and address many healthcare needs of children and adolescents with Down syndrome beyond that which is provided in primary care settings. (c) 2013 Wiley Periodicals, Inc. C1 [Skotko, Brian G.] Massachusetts Gen Hosp, Dept Pediat, Div Genet, Boston, MA 02114 USA. [Davidson, Emily Jean] Boston Childrens Hosp, Div Dev Med, Dev Med Ctr, Boston, MA USA. [Davidson, Emily Jean] Boston Childrens Hosp, Div Gen Pediat, Dev Med Ctr, Dept Med, Boston, MA USA. [Weintraub, Gil S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Skotko, BG (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Room 2222, Boston, MA 02114 USA. EM bskotko@partners.org RI Skotko, Brian/D-1375-2013 OI Skotko, Brian/0000-0002-5232-9882 NR 41 TC 9 Z9 9 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR PY 2013 VL 161A IS 3 BP 430 EP 437 DI 10.1002/ajmg.a.35795 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 095NQ UT WOS:000315341700004 PM 23401090 ER PT J AU Waxler, JL Cherniske, EM Dieter, K Herd, P Pober, BR AF Waxler, Jessica L. Cherniske, Elizabeth M. Dieter, Kristen Herd, Pamela Pober, Barbara R. TI Hearing from parents: The impact of receiving the diagnosis of Williams syndrome in their child SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE breaking bad news; Williams syndrome; WilliamsBeuren syndrome; diagnostic process; parental recollections ID BREAKING BAD-NEWS; DOWN-SYNDROME; QUALITATIVE-ANALYSIS; POSTNATAL DIAGNOSIS; DIFFICULT NEWS; GUIDELINES; EXPERIENCE AB Healthcare providers often share difficult or life-altering news with their patients yet this challenging and delicate process is frequently met with dissatisfaction by those receiving this news. Articles and guidelines exist to aid providers in sharing diagnoses such as Down syndrome, but relatively few have focused on rare genetic conditions often diagnosed years after birth. For this reason, we sought to learn about the experience of receiving a diagnosis from parents of children with Williams syndrome. We asked members of the Williams Syndrome Association to complete an anonymous online survey about recollections related to the diagnostic process. Responses, both close-ended and open-ended, were received from 600 families across the United States. Analysis revealed a high proportion of families (59.91%) with at least some negative recollections about the experience (and nearly half of those with negative recollections denied recalling anything positive). Factors influencing a more positive overall perception of the experience included receiving written information about Williams syndrome and seeing a genetic counselor. Analysis of open-ended responses identified additional positive and negative themes; for example, nearly one quarter of respondents expressed a desire to be given hope when receiving the diagnosis. Based on these analyses, we offer several specific recommendations for improving the diagnostic process in the future. (c) 2013 Wiley Periodicals, Inc. C1 [Waxler, Jessica L.; Pober, Barbara R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cherniske, Elizabeth M.] Yale Univ, Sch Med, New Haven, CT USA. [Dieter, Kristen] NW Reprod Genet, Chicago, IL USA. [Herd, Pamela] Univ Wisconsin, Madison, WI USA. [Pober, Barbara R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Waxler, JL (reprint author), 175 Cambridge St,Room 502, Boston, MA 02114 USA. EM jwaxler@partners.org NR 29 TC 3 Z9 3 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR PY 2013 VL 161A IS 3 BP 534 EP 541 DI 10.1002/ajmg.a.35789 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 095NQ UT WOS:000315341700017 PM 23401422 ER PT J AU Perry, LJP Jakobiec, FA Zakka, FR Reichel, E Herwig, MC Perry, A Brat, DJ Grossniklaus, HE AF Perry, Lynn J. Poole Jakobiec, Frederick A. Zakka, Fouad R. Reichel, Elias Herwig, Martina C. Perry, Arie Brat, Daniel J. Grossniklaus, Hans E. TI Reactive Retinal Astrocytic Tumors (So-called Vasoproliferative Tumors): Histopathologic, Immunohistochemical, and Genetic Studies of Four Cases SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GIANT-CELL ASTROCYTOMA; SUBRETINAL FIBROSIS; NEUROFIBROMATOSIS TYPE-2; PHOTODYNAMIC THERAPY; SURGICAL-MANAGEMENT; ROSENTHAL FIBERS; UVEITIS SYNDROME; OCULAR FUNDUS; BRAIN-TUMORS; PARS-PLANA AB PURPOSE: To evaluate the cellular nature of and diagnostic terminology used in connection with acquired retinal "vasoproliferative tumors." DESIGN: Retrospective clinicopathologic study. METHODS: Clinical records and microscopic slides of 4 enucleated globes were reviewed. Special stains and immunohistochemical probes for CD31, CD34, p53, glial fibrillary acidic protein (GFAP), CD163, and Ki67 (cell replication) were employed; ultrastructural and fluorescence in situ hybridization (FISH) analyses were performed. RESULTS: Tumors were located inferotemporally in middle-aged patients. They were uniformly composed of compacted elongated, GFAP-positive spindle cells (due to intermediate filaments identified ultrastructurally) with a Ki67 index of less than 1%. Rosenthal fibers and eosinophilic granular bodies were observed. Hyalinized periodic acid Schiff-positive vessels were widely separated. CD31 and CD34 revealed a sparse microvasculature. Tumor-associated exudate spread predominantly subretinally. The retinal pigment epithelium had undergone extensive placoid fibrous metaplasia with focal ossification. P53 upregulation, BRAF-KIAA gene rearrangement, and IDH1 R132H mutation typically associated with low-grade astrocytic neoplasms were absent. CONCLUSIONS: Retinal "vasoproliferative" tumors have been mischaracterized, because they actually display a paucity of microvessels. Proliferating fibrous astrocytes with a very low proliferation index predominate, without immunohistochemical or genetic evidence favoring a neoplasm. Subretinal exudate appeared capable of provoking widespread fibrous metaplasia of the pigment epithelium that was mainly responsible for secondary retinal damage. The term "reactive retinal astrocytic tumor" is proposed as more appropriate for this entity. In carefully selected progressive lesions, consideration should be given to earlier surgical intervention before extensive subretinal exudate accumulates and pigment epithelial proliferation with fibrous metaplasia ensues. (Am J Ophthalmol 2013;155:593-608. (C) 2013 by Elsevier Inc. All rights reserved.) C1 [Perry, Lynn J. Poole; Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Perry, Lynn J. Poole; Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cogan Eye Pathol Lab, Boston, MA USA. [Reichel, Elias] Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. [Herwig, Martina C.] Univ Bonn, Dept Ophthalmol, Bonn, Germany. [Perry, Arie] UCSF Sch Med, Dept Pathol & Lab Med, San Francisco, CA USA. [Herwig, Martina C.; Brat, Daniel J.; Grossniklaus, Hans E.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Grossniklaus, Hans E.] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu OI Perry, Arie/0000-0002-8300-7261 FU Heed Ophthalmic Foundation; Emory University [NIH/NEI p30 ey06360]; RPB Inc, New York, New York FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. The authors report rib financial disclosures. L.J.P.P. is supported in part by a Heed Ophthalmic Foundation fellowship. Funding through Emory University is provided by a departmental core grant (NIH/NEI p30 ey06360) and unrestricted grant from RPB Inc, New York, New York. Contributions of authors: design of study (L.P., F.A.J., H.G.); conduct of study (L.P., F.A.J., H.G., F.Z., M.H., A.P., D.B., E.R.); analysis of data (L.P., F.A.J., H.G., M.H., A.P., D.B., E.R.); and manuscript preparation (L.P., F.A.J., E.R., H.G.). NR 70 TC 9 Z9 9 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2013 VL 155 IS 3 BP 593 EP 608 DI 10.1016/j.ajo.2012.09.002 PG 16 WC Ophthalmology SC Ophthalmology GA 096TA UT WOS:000315426000024 ER PT J AU Shi, Y Pulliam, DA Liu, YH Hamilton, RT Jernigan, AL Bhattacharya, A Sloane, LB Qi, WB Chaudhuri, A Buffenstein, R Ungvari, Z Austad, SN Van Remmen, H AF Shi, Yun Pulliam, Daniel A. Liu, Yuhong Hamilton, Ryan T. Jernigan, Amanda L. Bhattacharya, Arunabh Sloane, Lauren B. Qi, Wenbo Chaudhuri, Asish Buffenstein, Rochelle Ungvari, Zoltan Austad, Steven N. Van Remmen, Holly TI Reduced mitochondrial ROS, enhanced antioxidant defense, and distinct age-related changes in oxidative damage in muscles of long-lived Peromyscus leucopus SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE Peromyscus leucopus; mitochondria; reactive oxygen species; skeletal muscle; oxidative damage; comparative biology of aging ID HYDROGEN-PEROXIDE PRODUCTION; SKELETAL-MUSCLE; UNCOUPLING PROTEIN-3; SUPEROXIDE-DISMUTASE; ELECTRON-TRANSPORT; STRESS RESISTANCE; MOUSE HINDLIMB; FIBER TYPES; LONGEVITY; MICE AB Shi Y, Pulliam DA, Liu Y, Hamilton RT, Jernigan AL, Bhattacharya A, Sloane LB, Qi W, Chaudhuri A, Buffenstein R, Ungvari Z, Austad SN, Van Remmen H. Reduced mitochondrial ROS, enhanced antioxidant defense, and distinct age-related changes in oxidative damage in muscles of long-lived Peromyscus leucopus. Am J Physiol Regul Integr Comp Physiol 304: R343-R355, 2013. First published January 16, 2013; doi:10.1152/ajpregu.00139.2012.-Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus. C1 [Shi, Yun; Pulliam, Daniel A.; Liu, Yuhong; Hamilton, Ryan T.; Jernigan, Amanda L.; Bhattacharya, Arunabh; Sloane, Lauren B.; Qi, Wenbo; Chaudhuri, Asish; Buffenstein, Rochelle; Austad, Steven N.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Shi, Yun; Pulliam, Daniel A.; Liu, Yuhong; Hamilton, Ryan T.; Jernigan, Amanda L.; Bhattacharya, Arunabh; Qi, Wenbo; Austad, Steven N.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cell & Struct Biol, San Antonio, TX 78245 USA. [Chaudhuri, Asish] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78245 USA. [Buffenstein, Rochelle; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Chaudhuri, Asish; Van Remmen, Holly] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu FU NCCIH NIH HHS [R01 AT006526]; NIA NIH HHS [R01 AG022891]; NINDS NIH HHS [R01 NS056218] NR 71 TC 16 Z9 17 U1 0 U2 32 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 2013 VL 304 IS 5 BP R343 EP R355 DI 10.1152/ajpregu.00139.2012 PG 13 WC Physiology SC Physiology GA 100DY UT WOS:000315677200003 PM 23325454 ER PT J AU Bouley, R Nunes, P Andriopoulos, B McLaughlin, M Webber, MJ Lin, HY Babitt, JL Gardella, TJ Ausiello, DA Brown, D AF Bouley, Richard Nunes, Paula Andriopoulos, Billy, Jr. McLaughlin, Margaret Webber, Matthew J. Lin, Herbert Y. Babitt, Jodie L. Gardella, Thomas J. Ausiello, Dennis A. Brown, Dennis TI Heterologous downregulation of vasopressin type 2 receptor is induced by transferrin SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE G protein-coupled receptor; endocytosis; antidiuretic hormone; kidney epithelial cells ID PROTEIN-COUPLED RECEPTORS; NEPHROGENIC DIABETES-INSIPIDUS; CLATHRIN-MEDIATED ENDOCYTOSIS; MEDULLARY COLLECTING DUCT; BONE-MARROW-CELLS; V-2 MESSENGER-RNA; EPITHELIAL-CELLS; LYSOSOMAL DEGRADATION; BETA-ARRESTIN; INTERNALIZATION AB Bouley R, Nunes P, Andriopoulos Jr. B, McLaughlin M, Webber MJ, Lin HY, Babitt JL, Gardella TJ, Ausiello DA, Brown D. Heterologous downregulation of vasopressin type 2 receptor is induced by transferrin. Am J Physiol Renal Physiol 304: F553-F564, 2013. First published December 12, 2012; doi:10.1152/ajprenal.00438.2011.-Vasopressin (VP) binds to the vasopressin type 2 receptor (V2R) to trigger physiological effects including body fluid homeostasis and blood pressure regulation. Signaling is terminated by receptor downregulation involving clathrin-mediated endocytosis and V2R degradation. We report here that both native and epitope-tagged V2R are internalized from the plasma membrane of LLC-PK1 kidney epithelial cells in the presence of another ligand, transferrin (Tf). The presence of iron-saturated Tf (holo-Tf; 4 h) reduced V2R binding sites at the cell surface by up to 33% while iron-free (apo-Tf) had no effect. However, no change in green fluorescent protein-tagged V2R distribution was observed in the presence of bovine serum albumin, atrial natriuretic peptide, or ANG II. Conversely, holo-Tf did not induce the internalization of another G protein-coupled receptor, the parathyroid hormone receptor. In contrast to the effect of VP, Tf did not increase intracellular cAMP or modify aquaporin-2 distribution in these cells, although addition of VP and Tf together augmented VP-induced V2R internalization. Tf receptor coimmunoprecipitated with V2R, suggesting that they interact closely, which may explain the additive effect of VP and Tf on V2R endocytosis. Furthermore, Tf-induced V2R internalization was abolished in cells expressing a dominant negative dynamin (K44A) mutant, indicating the involvement of clathrin-coated pits. We conclude that Tf can induce heterologous downregulation of the V2R and this might desensitize VP target cells without activating downstream V2R signaling events. It also provides new insights into urine-concentrating defects observed in rat models of hemochromatosis. C1 [Bouley, Richard; Nunes, Paula; Andriopoulos, Billy, Jr.; McLaughlin, Margaret; Webber, Matthew J.; Lin, Herbert Y.; Babitt, Jodie L.; Ausiello, Dennis A.; Brown, Dennis] Massachusetts Gen Hosp, Nephrol Div, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Bouley, Richard; Nunes, Paula; Andriopoulos, Billy, Jr.; McLaughlin, Margaret; Webber, Matthew J.; Lin, Herbert Y.; Babitt, Jodie L.; Gardella, Thomas J.; Ausiello, Dennis A.; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, MGH Ctr Syst Biol, Program Membrane Biol,Nephrol Div, 185 Cambridge St, Boston, MA 02114 USA. EM bouley.richard@mgh.harvard.edu RI Nunes-Hasler, Paula/N-4337-2015; OI Nunes-Hasler, Paula/0000-0002-4598-685X; Webber, Matthew/0000-0003-1092-4410 FU National Institutes of Health (NIH) [PO1DK38452, DK96586]; National Kidney Foundation; Doctoral Level Postgraduate Scholarship from National Sciences and Engineering Research Council; NIH [K08 DK-075846, RO1 DK063016, ROI DK069533, ROI 071837, DK11794]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43351] FX This work was supported by National Institutes of Health (NIH) Grants PO1DK38452 (to D. Brown and D. A. Ausiello) and DK96586 (to D. Brown). R. Bouley received an investigator award from the National Kidney Foundation. P. Nunes was supported by a Doctoral Level Postgraduate Scholarship from National Sciences and Engineering Research Council. J. L. Babitt was supported by NIH Grants K08 DK-075846 and RO1 DK063016. Dr. Lin is supported by NIH Grants ROI DK069533 and ROI 071837. Dr. T. J. Gardella is supported by NIH Grant DK11794. The Microscopy Core facility of the MGH Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (Grant DK57521) and the Center for the Study of Inflammatory Bowel Disease (Grant DK43351). NR 74 TC 2 Z9 2 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2013 VL 304 IS 5 BP F553 EP F564 DI 10.1152/ajprenal.00438.2011 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 100ER UT WOS:000315679500012 PM 23235478 ER PT J AU Vedovelli, L Rothermel, JT Finberg, KE Wagner, CA Azroyan, A Hill, E Breton, S Brown, D Paunescu, TG AF Vedovelli, Luca Rothermel, John T. Finberg, Karin E. Wagner, Carsten A. Azroyan, Anie Hill, Eric Breton, Sylvie Brown, Dennis Paunescu, Teodor G. TI Altered V-ATPase expression in renal intercalated cells isolated from B1 subunit-deficient mice by fluorescence-activated cell sorting SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE vacuolar H+-ATPase; proton pump; urinary acidification; pH homeostasis; Atp6v1b1(-/-) mice; collecting duct ID VACUOLAR H+-ATPASE; EPIDIDYMAL CLEAR CELLS; MEDULLARY COLLECTING DUCT; MALE REPRODUCTIVE-TRACT; EPITHELIAL-CELLS; PROTEIN-KINASE; TUBULAR-ACIDOSIS; B2 SUBUNIT; ADENOSINE-TRIPHOSPHATASE; LUMINAL ACIDIFICATION AB Vedovelli L, Rothermel JT, Finberg KE, Wagner CA, Azroyan A, Hill E, Breton S, Brown D, Paunescu TG. Altered V-ATPase expression in renal intercalated cells isolated from B1 subunit-deficient mice by fluorescence-activated cell sorting. Am J Physiol Renal Physiol 304: F522-F532, 2013. First published December 26, 2012; doi:10.1152/ajprenal.00394.2012.-Unlike human patients with mutations in the 56-kDa B1 subunit isoform of the vacuolar proton-pumping ATPase (V-ATPase), B1-deficient mice (Atp6v1b1(-/-)) do not develop metabolic acidosis under baseline conditions. This is due to the insertion of V-ATPases containing the alternative B2 subunit isoform into the apical membrane of renal medullary collecting duct intercalated cells (ICs). We previously reported that quantitative Western blots (WBs) from whole kidneys showed similar B2 protein levels in Atp6v1b1(-/-) and wild-type mice (Paunescu TG, Russo LM, Da Silva N, Kovacikova J, Mohebbi N, Van Hoek AN, McKee M, Wagner CA, Breton S, Brown D. Am J Physiol Renal Physiol 293: F1915-F1926, 2007). However, WBs from renal medulla (including outer and inner medulla) membrane and cytosol fractions reveal a decrease in the levels of the ubiquitous V-ATPase E1 subunit. To compare V-ATPase expression specifically in ICs from wild-type and Atp6v1b1(-/-) mice, we crossed mice in which EGFP expression is driven by the B1 subunit promoter (EGFP-B1(-/-) mice) with Atp6v1b1(-/-) mice to generate novel EGFP-B1(-/-) mice. We isolated pure IC populations by fluorescence-assisted cell sorting from EGFP-B1(-/-) and EGFP-B1(-/-) mice to compare their V-ATPase subunit protein levels. We report that V-ATPase A, E1, and H subunits are all significantly downregulated in EGFP-B1(-/-) mice, while the B2 protein level is considerably increased in these animals. We conclude that under baseline conditions B2 upregulation compensates for the lack of B1 and is sufficient to maintain basal acid-base homeostasis, even when other V-ATPase subunits are downregulated. C1 [Vedovelli, Luca; Rothermel, John T.; Azroyan, Anie; Hill, Eric; Breton, Sylvie; Brown, Dennis; Paunescu, Teodor G.] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Vedovelli, Luca; Rothermel, John T.; Azroyan, Anie; Hill, Eric; Breton, Sylvie; Brown, Dennis; Paunescu, Teodor G.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Vedovelli, Luca; Rothermel, John T.; Azroyan, Anie; Hill, Eric; Breton, Sylvie; Brown, Dennis; Paunescu, Teodor G.] Harvard Univ, Sch Med, Boston, MA USA. [Vedovelli, Luca] Univ Padua, Dept Pharmacol & Anesthesiol, Padua, Italy. [Finberg, Karin E.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. [Wagner, Carsten A.] Univ Zurich, Inst Physiol, Zurich, Switzerland. [Wagner, Carsten A.] Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. RP Paunescu, TG (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Program Membrane Biol, 185 Cambridge St,CPZN8150, Boston, MA 02114 USA. EM Paunescu.Teodor@mgh.harvard.edu OI Vedovelli, Luca/0000-0003-4847-2333 FU National Institutes of Health (NIH) [73266, DK-42956, DK-97124, HD-40793]; Swiss National Research Foundation Grant [31003A_138143/1]; Boston Area Diabetes and Endocrinology Research Center [NIH DK-57521]; Center for the Study of Inflammatory Bowel Disease [NIH DK-43341] FX This work was supported by National Institutes of Health (NIH) Grants DK-73266 (to T. G. Paunescu), DK-42956 (to D. Brown), DK-97124 (to S. Breton), and HD-40793 (to S. Breton) and by Swiss National Research Foundation Grant 31003A_138143/1 (to C. A. Wagner). The Microscopy Core Facility of the Program in Membrane Biology received additional support from the Boston Area Diabetes and Endocrinology Research Center (NIH DK-57521) and from the Center for the Study of Inflammatory Bowel Disease (NIH DK-43341). NR 48 TC 9 Z9 9 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2013 VL 304 IS 5 BP F522 EP F532 DI 10.1152/ajprenal.00394.2012 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 100ER UT WOS:000315679500009 PM 23269648 ER PT J AU Mengel, M Campbell, P Gebel, H Randhawa, P Rodriguez, ER Colvin, R Conway, J Hachem, R Halloran, PF Keshavjee, S Nickerson, P Murphey, C O'Leary, J Reeve, J Tinckam, K Reed, EF AF Mengel, M. Campbell, P. Gebel, H. Randhawa, P. Rodriguez, E. R. Colvin, R. Conway, J. Hachem, R. Halloran, P. F. Keshavjee, S. Nickerson, P. Murphey, C. O'Leary, J. Reeve, J. Tinckam, K. Reed, E. F. TI Precision Diagnostics in Transplantation: From Bench to Bedside SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Antibody-testing; Banff; precision diagnostics; transplantation ID ANTIBODY-MEDIATED REJECTION; DONOR-SPECIFIC ANTIBODIES; HLA-SPECIFIC ANTIBODIES; BRONCHIOLITIS OBLITERANS SYNDROME; RENAL-ALLOGRAFT REJECTION; POSITIVE CROSS-MATCH; LUNG TRANSPLANTATION; KIDNEY-TRANSPLANTATION; C1Q ASSAY; BANFF AB The Canadian and American Societies of Transplantation held a symposium on February 22, 2012 in Quebec City focused on discovery, validation and translation of new diagnostic tools into clinical transplantation. The symposium focused on antibody testing, transplantation pathology, molecular diagnostics and laboratory support for the incompatible patient. There is an unmet need for more precise diagnostic approaches in transplantation. Significant potential for increasing the diagnostic precision in transplantation was recognized through the integration of conventional histopathology, molecular technologies and sensitive antibody testing into one enhanced diagnostic system. C1 [Mengel, M.; Campbell, P.; Halloran, P. F.; Reeve, J.] Univ Alberta, Edmonton, AB, Canada. [Gebel, H.] Emory Univ, Atlanta, GA 30322 USA. [Randhawa, P.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Rodriguez, E. R.] Cleveland Clin, Cleveland, OH 44106 USA. [Colvin, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Conway, J.; Keshavjee, S.; Tinckam, K.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Hachem, R.] Washington Univ, St Louis, MO USA. [Nickerson, P.] Univ Manitoba, Winnipeg, MB, Canada. [Murphey, C.] Southwest Immunodiagnost Inc, San Antonio, TX USA. [O'Leary, J.] Baylor Univ, Med Ctr, Dallas, TX USA. [Reed, E. F.] Univ Calif Los Angeles, Los Angeles, CA USA. EM mmengel@ualberta.ca RI Halloran, Philip/J-1390-2012; OI Halloran, Philip/0000-0003-1371-1947; Tinckam, Kathryn/0000-0002-6638-2887; Nickerson, Peter/0000-0002-7393-7799 NR 66 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2013 VL 13 IS 3 BP 562 EP 568 DI 10.1111/j.1600-6143.2012.04344.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 097CW UT WOS:000315452600008 PM 23279692 ER PT J AU Shen, X Dong, YL Xu, ZP Wang, H Miao, CH Soriano, SG Sun, DD Baxter, MG Zhang, YY Xie, ZC AF Shen, Xia Dong, Yuanlin Xu, Zhipeng Wang, Hui Miao, Changhong Soriano, Sulpicio G. Sun, Dandan Baxter, Mark G. Zhang, Yiying Xie, Zhongcong TI Selective Anesthesia-induced Neuroinflammation in Developing Mouse Brain and Cognitive Impairment SO ANESTHESIOLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; NF-KAPPA-B; ENVIRONMENTAL ENRICHMENT; GENERAL-ANESTHESIA; NERVOUS-SYSTEM; CASPASE ACTIVATION; CARDIAC-SURGERY; EARLY EXPOSURE; PROTEIN-LEVELS; IMMUNE-SYSTEM AB Background: Recent population studies have suggested that children with multiple exposures to anesthesia and surgery at an early age are at an increased risk of cognitive impairment. The authors therefore have established an animal model with single versus multiple exposures of anesthetic(s) in young versus adult mice, aiming to distinguish the role of different types of anesthesia in cognitive impairment. Methods: Six-and 60-day-old mice were exposed to various anesthesia regimens. The authors then determined the effects of the anesthesia on learning and memory function, levels of proinflammatory cytokine interleukin-6 and tumor necrosis factor-alpha in brain tissues, and the amount of ionized calcium-binding adaptor molecule 1-positive cells, the marker of microglia activation, in the hippocampus. Results: In this article, the authors show that anesthesia with 3% sevoflurane for 2 h daily for 3 days induced cognitive impairment and neuroinflammation (e.g., increased interleukin-6 levels, 151 +/- 2.3% [mean +/- SD] vs. 100 +/- 9.0%, P = 0.035, n = 6) in young but not in adult mice. Anesthesia with 3% sevoflurane for 2 h daily for 1 day and 9% desflurane for 2 h daily for 3 days induced neither cognitive impairment nor neuroinflammation. Finally, an enriched environment and antiinflammatory treatment (ketorolac) ameliorated the sevoflurane-induced cognitive impairment. Conclusions: Anesthesia-induced cognitive impairment may depend on developmental stage, anesthetic agent, and number of exposures. These findings also suggest the cellular basis and the potential prevention and treatment strategies for anesthesia-induced cognitive impairment, which may ultimately lead to safer anesthesia care and better postoperative outcomes for children. C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health, Bethesda, Maryland [R21AG029856, R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, Illinois; Cure Alzheimer's Fund, Wellesley, Massachusetts FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts. Submitted for publication June 21, 2012. Accepted for publication October 19, 2012. This research was supported by grants R21AG029856, R21AG038994, R01 GM088801, and R01 AG041274 from the National Institutes of Health, Bethesda, Maryland; an investigator-initiated research grant from the Alzheimer's Association, Chicago, Illinois; and Cure Alzheimer's Fund, Wellesley, Massachusetts (to Dr. Xie). Anesthetic sevoflurane and desflurane were generously provided by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Drs. Shen and Dong contributed equally to this work. NR 69 TC 90 Z9 107 U1 4 U2 33 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2013 VL 118 IS 3 BP 502 EP 515 DI 10.1097/ALN.0b013e3182834d77 PG 14 WC Anesthesiology SC Anesthesiology GA 093LH UT WOS:000315192900009 PM 23314110 ER PT J AU Zheng, H Dong, YL Xu, ZP Crosby, G Culley, DJ Zhang, YY Xie, ZC AF Zheng, Hui Dong, Yuanlin Xu, Zhipeng Crosby, Gregory Culley, Deborah J. Zhang, Yiying Xie, Zhongcong TI Sevoflurane Anesthesia in Pregnant Mice Induces Neurotoxicity in Fetal and Offspring Mice SO ANESTHESIOLOGY LA English DT Article ID NF-KAPPA-B; TRAUMATIC BRAIN-INJURY; AMYLOID PROTEIN-LEVELS; ENVIRONMENTAL ENRICHMENT; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; SYSTEMIC INFECTION; SYNAPSE LOSS; ISOFLURANE; ACTIVATION AB Background: Each year, over 75,000 pregnant women in the United States undergo anesthesia care. The authors set out to assess the effects of the anesthetic sevoflurane on neurotoxicity in pregnant mice and on learning and memory in fetal and offspring mice. Methods: Pregnant mice (gestational day 14) and mouse primary neurons were treated with 2.5% sevoflurane for 2 h and 4.1% sevoflurane for 6 h, respectively. Brain tissues of both fetal and offspring mice (P31) and the primary neurons were harvested and subjected to Western blot and immunohistochemistry to assess interleukin-6, the synaptic markers postsynaptic density-95 and synaptophysin, and caspase-3 levels. Separately, learning and memory function in the offspring mice was determined in the Morris water maze. Results: Sevoflurane anesthesia in pregnant mice induced caspase-3 activation, increased interleukin-6 levels (256 +/- 50.98% [ mean +/- SD] vs. 100 +/- 54.12%, P = 0.026), and reduced postsynaptic density-95 (61 +/- 13.53% vs. 100 +/- 10.08%, P = 0.036) and synaptophysin levels in fetal and offspring mice. The sevoflurane anesthesia impaired learning and memory in offspring mice at P31. Moreover, interleukin-6 antibody mitigated the sevoflurane-induced reduction in postsynaptic density-95 levels in the neurons. Finally, environmental enrichment attenuated the sevoflurane- induced increases in interleukin-6 levels, reductions of synapse markers, and learning and memory impairment. Conclusions: These results suggest that sevoflurane may induce detrimental effects in fetal and offspring mice, which can be mitigated by environmental enrichment. These findings should promote more studies to determine the neurotoxicity of anesthesia in the developing brain. C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health, Bethesda, Maryland [R21AG029856, R21AG038994, R01 GM088801]; Cure Alzheimer's Fund, Wellesley, Massachusetts FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Submitted for publication March 14, 2012. Accepted for publication August 14, 2012. Supported by grants R21AG029856, R21AG038994, and R01 GM088801 from the National Institutes of Health, Bethesda, Maryland; and from Cure Alzheimer's Fund, Wellesley, Massachusetts (to Dr. Xie). The cost of anesthetic sevoflurane was generously provided by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Drs. Zheng and Dong contributed equally to this work. NR 55 TC 46 Z9 53 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2013 VL 118 IS 3 BP 516 EP 526 DI 10.1097/ALN.0b013e3182834d5d PG 11 WC Anesthesiology SC Anesthesiology GA 093LH UT WOS:000315192900010 PM 23314109 ER PT J AU Ahn, Y Gorlinger, K Alam, HB Eikermann, M AF Ahn, Young Goerlinger, Klaus Alam, Hasan B. Eikermann, Matthias TI Case Scenario: Pain-associated Respiratory Failure in Chest Trauma SO ANESTHESIOLOGY LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; PARTIAL THROMBOPLASTIN TIME; REGIONAL-ANESTHESIA; EPIDURAL HEMATOMA; HYPERCOAGULABLE STATE; DIABETES-MELLITUS; PROTHROMBIN TIME; CLOPIDOGREL; PATIENT; MANAGEMENT C1 [Ahn, Young; Goerlinger, Klaus; Alam, Hasan B.; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM meikermann@partners.org NR 45 TC 4 Z9 4 U1 0 U2 1 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 MAR PY 2013 VL 118 IS 3 BP 701 EP 708 DI 10.1097/ALN.0b013e318283996b PG 8 WC Anesthesiology SC Anesthesiology GA 093LH UT WOS:000315192900026 PM 23403516 ER PT J AU Odden, MC Tager, IB Gansevoort, RT Bakker, SJL Fried, LF Newman, AB Katz, R Satterfield, S Harris, TB Sarnak, MJ Siscovick, D Shlipak, MG AF Odden, Michelle C. Tager, Ira B. Gansevoort, Ron T. Bakker, Stephan J. L. Fried, Linda F. Newman, Anne B. Katz, Ronit Satterfield, Suzanne Harris, Tamara B. Sarnak, Mark J. Siscovick, David Shlipak, Michael G. TI Hypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Chronic kidney insufficiency; Aged; Hypertension; Cholesterol; Obesity; Smoking ID SERUM CYSTATIN-C; URINARY ALBUMIN EXCRETION; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; RENAL DYSFUNCTION; BLOOD-PRESSURE; POPULATION; RISK; ATHEROSCLEROSIS; PREDICTORS AB Purpose: To determine if the associations among established risk factors and reduced kidney function vary by age. Methods: We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort. Results: Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 23 (95% confidence interval [CI], 0.1, 4.4), 5.1 (95% Cl, 4.1, 6.1), and 6.9 (95% CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80 years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95% CI, 3.5, 6.3), 7.1 (95% CI, 6.0, 83), 8.9 (95% CI, 5.4,11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest. Conclusions: Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults. (C) 2013 Elsevier Inc. All rights reserved. C1 [Odden, Michelle C.] Oregon State Univ, Sch Biol & Populat Hlth Sci, Corvallis, OR 97331 USA. [Tager, Ira B.] Univ Calif Berkeley, Dept Epidemiol, Berkeley, CA 94720 USA. [Gansevoort, Ron T.; Bakker, Stephan J. L.] Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Med, Hlth Sci Ctr, Memphis, TN 38104 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Dept Med, Boston, MA USA. [Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. RP Odden, MC (reprint author), Oregon State Univ, 321 Milam Hall, Corvallis, OR 97331 USA. EM Michelle.Odden@oregonstate.edu RI Newman, Anne/C-6408-2013; Bakker, Stephan/J-4023-2015 OI Newman, Anne/0000-0002-0106-1150; Bakker, Stephan/0000-0003-3356-6791 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; NHLBI [HL080295, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169]; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, R01AG027002]; National Institute of Nursing Research [R01-NR012459]; NIH, NIA; Dutch Kidney Foundation, Bussum, The Netherlands [E013]; National Institute of Diabetes and Digestive, and Kidney Diseases [T32DK07791, DK52866]; American Heart Association Western States Affiliate Clinical Research Program; National Institute on Aging [K01AG039387]; [R01-HL-63963-01A1] FX The Cardiovascular Health Study was supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grant HL080295, with additional contribution from National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA). See also http://www.chs-nhlbi.org/pi.htm. Health ABC was supported through the NIA contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050, and National Institute of Nursing Research grant R01-NR012459. In addition, this research was supported in part by the Intramural Research Program of the NIH, NIA. MESA was supported by grant R01-HL-63963-01A1 and by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the NHLBI. PREVEND is supported by grant E013 of the Dutch Kidney Foundation, Bussum, The Netherlands, and grants T32DK07791 and DK52866 from the National Institute of Diabetes and Digestive, and Kidney Diseases.; This project was also supported by grant R01AG027002 from the NIA. Dr. Odden is supported by a the American Heart Association Western States Affiliate Clinical Research Program and the National Institute on Aging (K01AG039387). NR 34 TC 8 Z9 8 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 2013 VL 23 IS 3 BP 106 EP 111 DI 10.1016/j.annepidem.2012.12.004 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 095XI UT WOS:000315367900002 PM 23313266 ER PT J AU Tanpowpong, P Broder-Fingert, S Obuch, JC Rahni, DO Katz, AJ Leffler, DA Kelly, CP Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Obuch, Joshua C. Rahni, David O. Katz, Aubrey J. Leffler, Daniel A. Kelly, Ciaran P. Camargo, Carlos A., Jr. TI Multicenter study on the value of ICD-9-CM codes for case identification of celiac disease SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Coding; Serology; Endoscopy; Administrative ID AT-RISK GROUPS; DIAGNOSIS; PREVALENCE; ASSOCIATION; MANAGEMENT; MORTALITY; ACCURACY AB Purpose: To evaluate the value of ICD-9-CM code for identifying celiac disease (CD). Methods: We searched administrative data to identify all adults with ICD-9-CM diagnosis code 579.0 (CD) at three teaching hospitals between 2000 and 2010. We then stratified patients according to the presence/absence of relevant serology and endoscopy codes into four groups: None, serology, endoscopy, and both. A diagnostic algorithm was applied to define CD status. Results: Through random sampling and appropriate weighting, the 1200 reviewed patients represented a cohort of 8,122 cases. The overall positive predictive value (PPV) of the ICD-9-CM code was 15% (95% confidence interval [CI], 13%-17%). Case identification by a diagnosis code alone had a PPV of 4%, whereas the group with diagnosis code plus both serology and endoscopy testing had a PPV of 49%. Independent predictors of CD were non-Hispanic white, ICD-9-CM coded patient group, total number of a diagnosis code, and receiving a diagnosis code by a gastroenterologist. The model had an area under the curve of 0.87 (95% CI, 0.84-0.89). Conclusions: The performance of ICD-9-CM 579.0 alone for identifying CD is extremely poor. Adding other readily available administrative data significantly improves CD case identification. The proposed case finding strategy via administrative databases may facilitate future research on CD. (C) 2013 Elsevier Inc. All rights reserved. C1 [Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp Children, Boston, MA 02115 USA. [Obuch, Joshua C.; Rahni, David O.; Leffler, Daniel A.; Kelly, Ciaran P.] Harvard Univ, Sch Med, Celiac Ctr, Boston, MA USA. [Obuch, Joshua C.; Rahni, David O.; Leffler, Daniel A.; Kelly, Ciaran P.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02215 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Sch Med, Boston, MA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Obuch, Joshua/0000-0003-3764-9869; Broder-Fingert, Sarabeth/0000-0002-0932-4461 NR 20 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 2013 VL 23 IS 3 BP 136 EP 142 DI 10.1016/j.annepidem.2012.12.009 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 095XI UT WOS:000315367900007 PM 23313264 ER PT J AU Zatzick, D Jurkovich, G Rivara, FP Russo, J Wagner, A Wang, J Dunn, C Lord, SP Petrie, M O'Connor, SS Katon, W AF Zatzick, Douglas Jurkovich, Gregory Rivara, Frederick P. Russo, Joan Wagner, Amy Wang, Jin Dunn, Chris Lord, Sarah Peregrine Petrie, Megan O'Connor, Stephen S. Katon, Wayne TI A Randomized Stepped Care Intervention Trial Targeting Posttraumatic Stress Disorder for Surgically Hospitalized Injury Survivors SO ANNALS OF SURGERY LA English DT Article DE injury; physical function; PTSD; stepped care; surgical hospitalization; traumatic brain injury ID COGNITIVE-BEHAVIORAL THERAPY; NATIONAL COMORBIDITY SURVEY; TRAUMATIC BRAIN-INJURY; COLLABORATIVE CARE; PREVENTIVE INTERVENTIONS; FUNCTIONAL OUTCOMES; POPULATION-IMPACT; ANXIETY DISORDERS; MAJOR TRAUMA; DEPRESSION AB Objective: To test the effectiveness of a stepped care intervention model targeting posttraumatic stress disorder (PTSD) symptoms after injury. Background: Few investigations have evaluated interventions for injured patients with PTSD and related impairments that can be feasibly implemented in trauma surgical settings. Methods: The investigation was a pragmatic effectiveness trial in which 207 acutely injured hospitalized trauma survivors were screened for high PTSD symptom levels and then randomized to a stepped combined care management, psychopharmacology, and cognitive behavioral psychotherapy intervention (n = 104) or usual care control (n = 103) conditions. The symptoms of PTSD and functional limitations were reassessed at 1, 3, 6, 9, and 12 months after the index injury admission. Results: Regression analyses demonstrated that over the course of the year after injury, intervention patients had significantly reduced PTSD symptoms when compared with controls [group by time effect, CAPS (Clinician-Administered PTSD Scale): F(2, 185) = 5.50, P < 0.01; PCL-C (PTSD Checklist Civilian Version): F(4, 185) = 5.45, P < 0.001]. Clinically and statistically significant PTSD treatment effects were observed at the 6-, 9-, and 12-month postinjury assessments. Over the course of the year after injury, intervention patients also demonstrated significant improvements in physical function [MOS SF-36 PCS (Medical Outcomes Study Short Form 36 Physical Component Summary) main effect: F(1, 172) = 9.87, P < 0.01]. Conclusions: Stepped care interventions can reduce PTSD symptoms and improve functioning over the course of the year after surgical injury hospitalization. Orchestrated investigative and policy efforts could systematically introduce and evaluate screening and intervention procedures for PTSD at US trauma centers. (Trial Registration: clinicaltrials.gov identifier: NCT00270959) C1 [Zatzick, Douglas; Russo, Joan; Wagner, Amy; Wang, Jin; Dunn, Chris; Lord, Sarah Peregrine; Petrie, Megan; O'Connor, Stephen S.; Katon, Wayne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Zatzick, Douglas; Jurkovich, Gregory; Rivara, Frederick P.; Wang, Jin; O'Connor, Stephen S.] Univ Washington, Sch Med, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. [Jurkovich, Gregory] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98104 USA. [Rivara, Frederick P.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98104 USA. [Wagner, Amy] Portland VA Med Ctr, Portland, OR USA. RP Zatzick, D (reprint author), Univ Washington, Sch Med, Harborview Injury Prevent & Res Ctr, 325 9th Ave,Box 359911, Seattle, WA 98104 USA. EM dzatzick@u.washington.edu FU National Institute of Mental Health [R01/MH073613, K24/MH086814] FX This work was supported by the National Institute of Mental Health grants R01/MH073613 and K24/MH086814 (Dr Zatzick). NR 55 TC 53 Z9 53 U1 7 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2013 VL 257 IS 3 BP 390 EP 399 DI 10.1097/SLA.0b013e31826bc313 PG 10 WC Surgery SC Surgery GA 088BN UT WOS:000314808900004 PM 23222034 ER PT J AU Borsook, D Kussman, BD George, E Becerra, LR Burke, DW AF Borsook, David Kussman, Barry D. George, Edward Becerra, Lino R. Burke, Dennis W. TI Surgically Induced Neuropathic Pain Understanding the Perioperative Process SO ANNALS OF SURGERY LA English DT Article DE analgesics; anesthesia; blockade; brain; centralization; central sensitization; genetic; near-infrared spectroscopy; nerve; preventive; surgery; trauma ID SOMATOSENSORY-EVOKED-POTENTIALS; RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER; SCIATIC-NERVE CONSTRICTION; LOWER-EXTREMITY AMPUTATION; LOWER-LIMB AMPUTATION; BYPASS GRAFT-SURGERY; POSTOPERATIVE PAIN; CENTRAL SENSITIZATION; PREEMPTIVE ANALGESIA AB Nerve damage takes place during surgery. As a consequence, significant numbers (10%-40%) of patients experience chronic neuropathic pain termed surgically induced neuropathic pain (SNPP). The initiating surgery and nerve damage set off a cascade of events that includes both pain and an inflammatory response, resulting in "peripheral and central sensitization," with the latter resulting from repeated barrages of neural activity from nociceptors. In affected patients, these initial events produce chemical, structural, and functional changes in the peripheral and central nervous systems (CNS). The maladaptive changes in damaged nerves lead to peripheral manifestations of the neuropathic state-allodynia, sensory loss, shooting pains, etc, that can manifest long after the effects of the surgical injury have resolved. The CNS manifestations that occur are termed "centralization of pain" and affect sensory, emotional, and other (eg, cognitive) systems as well as contributing to some of the manifestations of the chronic pain syndrome (eg, depression). Currently there are no objective measures of nociception and pain in the peri-operative period. As such, intermittent or continuous pain may take place during and after surgery. New technologies including direct measures of specific brain function of nociception and new insights into preoperative evaluation of patients including genetic predisposition, appear to provide initial opportunities for decreasing the burden of SNPP, until treatments with high efficacy and low adverse effects that either prevent or treat pain are discovered. C1 [Borsook, David; Kussman, Barry D.; Becerra, Lino R.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. [George, Edward] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Burke, Dennis W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA. EM david.borsook@childrens.harvard.edu FU NINDS [K24 NS064050] FX This work was supported by a grant from NINDS to DB (K24 NS064050). NR 170 TC 30 Z9 30 U1 4 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2013 VL 257 IS 3 BP 403 EP 412 DI 10.1097/SLA.0b013e3182701a7b PG 10 WC Surgery SC Surgery GA 088BN UT WOS:000314808900006 PM 23059501 ER PT J AU Merkow, RP Hall, BL Cohen, ME Wang, X Adams, JL Chow, WB Lawson, EH Bilimoria, KY Richards, K Ko, CY AF Merkow, Ryan P. Hall, Bruce L. Cohen, Mark E. Wang, Xue Adams, John L. Chow, Warren B. Lawson, Elise H. Bilimoria, Karl Y. Richards, Karen Ko, Clifford Y. TI Validity and Feasibility of the American College of Surgeons Colectomy Composite Outcome Quality Measure SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; colon surgery; outcomes; quality improvement; quality measure; surgery ID IMPROVEMENT PROGRAM; RISK-ADJUSTMENT; CARE; ASSOCIATION AB Objective: To develop a reliable, robust, parsimonious, risk-adjusted 30-day composite colectomy outcome measure. Background: A fundamental aspect in the pursuit of high-quality care is the development of valid and reliable performance measures in surgery. Colon resection is associated with appreciable morbidity and mortality and therefore is an ideal quality improvement target. Methods: From 2010 American College of Surgeons National Surgical Quality Improvement Program data, patients were identified who underwent colon resection for any indication. A composite outcome of death or any serious morbidity within 30 days of the index operation was established. A 6-predictor, parsimonious model was developed and compared with a more complex model with more variables. National caseload requirements were calculated on the basis of increasing reliability thresholds. Results: From 255 hospitals, 22,346 patients were accrued who underwent a colon resection in 2010, most commonly for neoplasm (46.7%). A mortality or serious morbidity event occurred in 4461 patients (20.0%). At the hospital level, the median composite event rate was 20.7% (interquartile range: 15.8%-26.3%). The parsimonious model performed similarly to the full model (Akaike information criterion: 19,411 vs 18,988), and hospital-level performance comparisons were highly correlated (R = 0.97). At a reliability threshold of 0.4, 56 annual colon resections would be required and achievable at an estimated 42% of US and 69% of American College of Surgeons National Surgical Quality Improvement Program hospitals. This 42% of US hospitals performed approximately 84% of all colon resections in the country in 2008. Conclusions: It is feasible to design a measure with a composite outcome of death or serious morbidity after colon surgery that has a low burden for data collection, has substantial clinical importance, and has acceptable reliability. C1 [Merkow, Ryan P.; Hall, Bruce L.; Cohen, Mark E.; Wang, Xue; Chow, Warren B.; Bilimoria, Karl Y.; Richards, Karen; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Colorado Denver, Dept Surg, Aurora, CO USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO 63130 USA. [Hall, Bruce L.] Barnes Jewish Hosp, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO 63130 USA. [Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Adams, John L.] RAND Corp, Santa Monica, CA USA. [Chow, Warren B.; Lawson, Elise H.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Chow, Warren B.; Lawson, Elise H.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Merkow, RP (reprint author), Amer Coll Surg, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM RMerkow@facs.org FU American College of Surgeons Clinical Scholars in Residence Program, Chicago, IL FX RPM and WBC are supported by the American College of Surgeons Clinical Scholars in Residence Program, Chicago, IL. BLH, JLA, and KYB are consultants to the ACS NSQIP. The authors declare no conflicts of interest. NR 23 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2013 VL 257 IS 3 BP 483 EP 489 DI 10.1097/SLA.0b013e318273bf17 PG 7 WC Surgery SC Surgery GA 088BN UT WOS:000314808900017 PM 23299518 ER PT J AU Liao, KP Kurreeman, F Li, G Duclos, G Murphy, S Guzman, R Cai, TX Gupta, N Gainer, V Schur, P Cui, J Denny, JC Szolovits, P Churchill, S Kohane, I Karlson, EW Plenge, RM AF Liao, Katherine P. Kurreeman, Fina Li, Gang Duclos, Grant Murphy, Shawn Guzman, Raul Cai, Tianxi Gupta, Namrata Gainer, Vivian Schur, Peter Cui, Jing Denny, Joshua C. Szolovits, Peter Churchill, Susanne Kohane, Isaac Karlson, Elizabeth W. Plenge, Robert M. TI Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and nonrheumatoid arthritis controls SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; CYCLIC CITRULLINATED PEPTIDE; CELIAC-DISEASE; DISCOVERY RESEARCH; HEALTH RECORDS; GENETIC-BASIS; PHENOME-WIDE; ANTI-CCP; VARIANTS AB Objective The significance of nonrheumatoid arthritis (RA) autoantibodies in patients with RA is unclear. The aim of this study was to assess associations of autoantibodies with autoimmune risk alleles and with clinical diagnoses from the electronic medical records (EMRs) among RA cases and non-RA controls. Methods Data on 1,290 RA cases and 1,236 non-RA controls of European genetic ancestry were obtained from the EMRs of 2 large academic centers. The levels of anticitrullinated protein antibodies (ACPAs), antinuclear antibodies (ANAs), antitissue transglutaminase antibodies (AGTAs), and antithyroid peroxidase (anti-TPO) antibodies were measured. All subjects were genotyped for autoimmune risk alleles, and the association between number of autoimmune risk alleles present and number of types of autoantibodies present was studied. A phenome-wide association study (PheWAS) was conducted to study potential associations between autoantibodies and clinical diagnoses among RA cases and non-RA controls. Results The mean ages were 60.7 years in RA cases and 64.6 years in non-RA controls. The proportion of female subjects was 79% in each group. The prevalence of ACPAs and ANAs was higher in RA cases compared to controls (each P < 0.0001); there were no differences in the prevalence of anti-TPO antibodies and AGTAs. Carriage of higher numbers of autoimmune risk alleles was associated with increasing numbers of autoantibody types in RA cases (P = 2.1 x 105) and non-RA controls (P = 5.0 x 103). From the PheWAS, the presence of ANAs was significantly associated with a diagnosis of Sjogren's/sicca syndrome in RA cases. Conclusion The increased frequency of autoantibodies in RA cases and non-RA controls was associated with the number of autoimmune risk alleles carried by an individual. PheWAS of EMR data, with linkage to laboratory data obtained from blood samples, provide a novel method to test for the clinical significance of biomarkers in disease. C1 [Liao, Katherine P.; Kurreeman, Fina; Li, Gang; Duclos, Grant; Schur, Peter; Cui, Jing; Karlson, Elizabeth W.; Plenge, Robert M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kurreeman, Fina; Gupta, Namrata; Plenge, Robert M.] Broad Inst, Cambridge, MA USA. [Kurreeman, Fina] Leiden Univ, Med Ctr, Leiden, Netherlands. [Murphy, Shawn; Guzman, Raul; Gainer, Vivian; Churchill, Susanne] Partners Healthcare, Charlestown, MA USA. [Murphy, Shawn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Denny, Joshua C.] Vanderbilt Univ, Nashville, TN USA. [Szolovits, Peter] MIT, Cambridge, MA 02139 USA. [Churchill, Susanne; Kohane, Isaac] I2b2 Ctr Biomed Comp, Boston, MA USA. [Kohane, Isaac] Harvard Univ, Sch Med, Boston, MA USA. RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St,PBB B3, Boston, MA 02115 USA. EM kliao@partners.org OI Szolovits, Peter/0000-0001-8411-6403 FU NIH [U54-LM-008748, K08-AR-060257, K24-AR-052403, R01-AR-049880, P60-AR-047782, R01-AR-057108, R01-AR-056768, U01-GM-092691, R01-AR-059648]; Burroughs Wellcome Fund FX Supported by NIH grant U54-LM-008748. Dr. Liao's work was supported by NIH grant K08-AR-060257 (the Katherine Swan Ginsburg Fund). Dr. Karlson's work was supported by NIH grants K24-AR-052403, R01-AR-049880, and P60-AR-047782. Dr. Plenge's work was supported by NIH grants R01-AR-057108, R01-AR-056768, U01-GM-092691, and R01-AR-059648. Dr. Plenge holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. NR 48 TC 29 Z9 29 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAR PY 2013 VL 65 IS 3 BP 571 EP 581 DI 10.1002/art.37801 PG 11 WC Rheumatology SC Rheumatology GA 097CU UT WOS:000315452400005 PM 23233247 ER PT J AU Agassandian, M Mallampalli, RK AF Agassandian, Marianna Mallampalli, Rama K. TI Surfactant phospholipid metabolism SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Surfactant; Apoprotein; Phospholipid ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; RESPIRATORY-DISTRESS-SYNDROME; FATTY-ACID SYNTHASE; HUMAN CARDIOLIPIN SYNTHASE; HUMAN-FETAL LUNG; ADULT-RAT LUNG; LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE 1; EARLY EMBRYONIC LETHALITY; CHOLINE-KINASE-ALPHA; II CELLS AB Pulmonary surfactant is essential for life and is composed of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant components, disaturated phosphatidylcholine that confers surface-tension lowering activities, and phosphatidylglycerol, recently implicated in innate immune defense. Future studies providing a better understanding of the molecular control and physiological relevance of minor surfactant lipid components are needed. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. (C) 2012 Elsevier B.V. All rights reserved. C1 [Agassandian, Marianna; Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence, Dept Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, UPMC Montefiore, Dept Med, NW 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174] FX The authors wish to thank Leah Kaercher for editorial assistance with the manuscript and preparation of the figures. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health RO1 grants HL096376, HL097376 and HL098174 (to R.K.M.). NR 272 TC 37 Z9 37 U1 4 U2 48 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD MAR PY 2013 VL 1831 IS 3 SI SI BP 612 EP 625 DI 10.1016/j.bbalip.2012.09.010 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 099IB UT WOS:000315613600015 PM 23026158 ER PT J AU Schroder, MS Gusenleitner, D Quackenbush, J Culhane, AC Haibe-Kains, B AF Schroeder, Markus S. Gusenleitner, Daniel Quackenbush, John Culhane, Aedn C. Haibe-Kains, Benjamin TI RamiGO: an R/Bioconductor package providing an AmiGO Visualize interface SO BIOINFORMATICS LA English DT Article ID METASTASIS AB The R/Bioconductor package RamiGO is an R interface to AmiGO that enables visualization of Gene Ontology (GO) trees. Given a list of GO terms, RamiGO uses the AmiGO visualize API to import Graphviz-DOT format files into R, and export these either as images (SVG, PNG) or into Cytoscape for extended network analyses. RamiGO provides easy customization of annotation, highlighting of specific GO terms, colouring of terms by P-value or export of a simplified summary GO tree. We illustrate RamiGO functionalities in a genome-wide gene set analysis of prognostic genes in breast cancer. C1 [Schroeder, Markus S.] Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland. [Schroeder, Markus S.; Gusenleitner, Daniel; Quackenbush, John; Culhane, Aedn C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Gusenleitner, Daniel] Boston Univ, Dept Bioinformat, Boston, MA 02215 USA. [Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Quackenbush, John; Culhane, Aedn C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Haibe-Kains, Benjamin] Inst Rech Clin Montreal, Bioinformat & Computat Genom Lab, Montreal, PQ H2W 1R7, Canada. RP Schroder, MS (reprint author), Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland. EM markus.schroeder@ucdconnect.ie RI Haibe-Kains, Benjamin/D-3702-2011 OI Haibe-Kains, Benjamin/0000-0002-7684-0079 FU National Human Genome Research Institute [1P50 HG004233]; Fulbright Commission for Educational Exchange; US National Institutes of Health [1U01CA151118-01A1, R01 LM010129-01]; Claudia Adams Barr Program in Innovative Basic Cancer Research; DFCI Breast Cancer SPORE, Dana-Farber Cancer Institute Women's Cancer Program [CA089393] FX This work was supported by the National Human Genome Research Institute (1P50 HG004233 to M. S. S.); Fulbright Commission for Educational Exchange to (B.H.-K.); US National Institutes of Health (#1U01CA151118-01A1 to J.Q., R01 LM010129-01 to B.H.-K. and J.Q.); Claudia Adams Barr Program in Innovative Basic Cancer Research (A. C. C. and J.Q.); Career Development grant from DFCI Breast Cancer SPORE: CA089393, Dana-Farber Cancer Institute Women's Cancer Program (to A.C.C). NR 7 TC 10 Z9 11 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 1 PY 2013 VL 29 IS 5 BP 666 EP 668 DI 10.1093/bioinformatics/bts708 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 099LO UT WOS:000315623000023 PM 23297033 ER PT J AU Armand, P AF Armand, Philippe TI Hyperferritinemia in Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID IRON OVERLOAD C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM parmand@partners.org NR 6 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2013 VL 19 IS 3 BP 336 EP 337 DI 10.1016/j.bbmt.2013.01.002 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 096SX UT WOS:000315425700002 PM 23295165 ER PT J AU Bolanos-Meade, J Wu, J Logan, BR Levine, JE Ho, VT Alousi, AM Weisdorf, DJ Luznik, L AF Bolanos-Meade, Javier Wu, Juan Logan, Brent R. Levine, John E. Ho, Vincent T. Alousi, Amin M. Weisdorf, Daniel J. Luznik, Leo CA Blood & Marrow Transplant Clinical TI Lymphocyte Phenotype during Therapy for Acute Graft-versus-Host Disease: A Brief Report from BMT-CTN 0302 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Flow cytometry; Chronic graft-versus-host-disease ID HEMATOPOIETIC-CELL TRANSPLANTATION; T-CELLS; MYCOPHENOLATE; PENTOSTATIN; ETANERCEPT; DENILEUKIN; TRIAL; BLOOD AB Although significant strides have been made in understanding the biology of graft-versus-host disease (GVHD) and its prevention over the last 4 decades, little is known about the different populations of lymphocytes and the changes in response to treatment for this condition. BMT-CTN 0302 was a randomized phase II clinical trial in the Blood and Marrow Transplant Clinical Trials Network that assessed the efficacy of combination therapy with steroids plus pentostatin, mycophenolate mofetil, etanercept, or denileukin diftitox in patients with acute GVHD. Patients enrolled in the study underwent blood analysis by flow cytometry on days 0, 14, and 28 of therapy to enumerate the number of total lymphocytes, T cells, B cells, and lymphocytes expressing activation markers. Baseline total lymphocyte counts and subpopulations were similar in the 4 treatment arms. Responding patients had a smaller decrease in total CD45(+) cell count (P = .005) compared with nonresponding patients at day 28. On univariate analysis, those who developed chronic GVHD had significantly higher CD8(+) cell counts at day 14 compared with those without it (P = .005). There was no significant association between baseline lymphocyte count and survival. On univariate analysis, among the patients with higher lymphocyte counts at days 14 and 28, there was a trend toward better survival at day 180, although this trend did not reach the predetermined threshold for significance. We found no significant differences in lymphocyte total or subpopulation counts among the 4 treatment arms, and no notable influence on outcomes. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Bolanos-Meade, Javier] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Wu, Juan] EMMES Corp, Rockville, MD USA. [Logan, Brent R.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Levine, John E.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Levine, John E.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA. [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Weisdorf, Daniel J.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. RP Bolanos-Meade, J (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Bunting Blaustein Canc Res Bldg,1650 Orleans St,R, Baltimore, MD 21231 USA. EM Fbolano2@jhmi.edu OI Levine, John/0000-0002-9133-0800 FU National Heart, Lung, and Blood Institute [U10HL069294]; National Cancer Institute; National Institute of Allergy and Infectious Disease FX Support for this study was provided by grant U10HL069294 from the National Heart, Lung, and Blood Institute, and the National Cancer Institute, along with contributions from Eisai, Hospira, Roche Laboratories, and Immunex Corporation, a wholly owned subsidiary of Amgen. Additional support was provided by the National Institute of Allergy and Infectious Disease for the ancillary studies "Analysis of Serum Biomarkers Related to aGVHD Treatment Responsiveness" and "Pharmacogenetics of Steroid Responsiveness in aGVHD." The analyses were performed independent of any of the study sponsors. NR 13 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2013 VL 19 IS 3 BP 481 EP 485 DI 10.1016/j.bbmt.2012.12.003 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 096SX UT WOS:000315425700023 PM 23247045 ER PT J AU Preston, MA Harisinghani, MG Mucci, L Witiuk, K Breau, RH AF Preston, Mark A. Harisinghani, Mukesh G. Mucci, Lorelei Witiuk, Kelsey Breau, Rodney H. TI Diagnostic tests in urology: magnetic resonance imaging (MRI) for the staging of prostate cancer SO BJU INTERNATIONAL LA English DT Article DE diagnostic test; prostate cancer; magnetic resonance imaging; MRI; evidence-based medicine ID METAANALYSIS C1 [Preston, Mark A.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Preston, Mark A.; Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Witiuk, Kelsey; Breau, Rodney H.] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Breau, Rodney H.] Univ Ottawa, Div Urol, Dept Surg, Ottawa, ON, Canada. [Preston, Mark A.; Breau, Rodney H.] Int Evidence Based Urol Working Grp, Gainesville, FL 32610 USA. RP Breau, RH (reprint author), Dept Surg, Div Urol, 501 Smyth Rd,Box 222, Ottawa, ON K1H 8L6, Canada. EM rodneybreau@yahoo.ca FU Canadian Urological Association Scholarship Foundation; AUA Northeastern Section Young Investigator Award; Prostate Cancer Canada Network FX Rodney H. Breau is supported by the Canadian Urological Association Scholarship Foundation, the AUA Northeastern Section Young Investigator Award, and Prostate Cancer Canada Network. NR 8 TC 3 Z9 3 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2013 VL 111 IS 3 BP 514 EP 517 DI 10.1111/j.1464-410X.2012.11447.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 096HQ UT WOS:000315395200038 PM 23320634 ER PT J AU Kazer, MW Bailey, DE Chipman, J Psutka, SP Hardy, J Hembroff, L Regan, M Dunn, RL Crociani, C Sanda, MG AF Kazer, Meredith Wallace Bailey, Donald E., Jr. Chipman, Jonathan Psutka, Sarah P. Hardy, Jill Hembroff, Larry Regan, Meredith Dunn, Rodney L. Crociani, Catrina Sanda, Martin G. CA PROSTQA Consortium Study Grp TI Uncertainty and perception of danger among patients undergoing treatment for prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; uncertainty; danger; treatment satisfaction ID QUALITY-OF-LIFE; INTERVENTION; SATISFACTION; MANAGEMENT; SURVIVORS AB Study Type Therapy (attitude prevalence) Level of Evidence2a What's known on the subject? and What does the study add? Marked differences in uncertainty among patients have been found relating to race and social environment indicating that as uncertainty increases, social functioning declines. Correlations have been found between uncertainty and patients' coping, psychological adjustment and perceptions of their health and illness. Studies suggest the detrimental effect of uncertainty among patients with prostate cancer in the perception of their quality of life. These studies underline the potential benefit of targeted intervention. The study provides a unique insight into the impact of uncertainty and perception of danger on overall satisfaction with treatment outcomes in men with prostate cancer. Its results suggest that possible disparities related to patient racial background and education may exist in the perception of cancer-related uncertainty. Racial and educational disparities, coupled with a mild to moderate association of uncertainty or danger perception and overall outcome satisfaction, suggest an unmet need for healthcare and nursing services for men undergoing treatment for prostate cancer. OBJECTIVES center dot To investigate patient uncertainty and perception of danger regarding prospects for clinical prostate cancer control. center dot To determine the impact of these factors on satisfaction with overall prostate cancer treatment outcome. PATIENTS AND METHODS center dot Men who had undergone primary treatment for early stage prostate cancer and who were participants in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) prospective cohort study of prostate cancer outcomes (the parent study) were offered the opportunity to participate in the present study. center dot Centralized phone interviews were conducted to determine patient-reported uncertainty regarding cancer status (measured by the Mishel Uncertainty in Illness Scale-Community Form), perception of danger (measured by Folkman and Lazarus' Appraisal Scale) and satisfaction with treatment outcome (measured by the Service Satisfaction Scale for Cancer Care). The study used the same centralized telephone interview centre as was used in the parent study. center dot Data were collected at 48, 60 or 72 months after the completion of prostate cancer treatment. center dot Relationships among measures were characterized by Spearman rank correlation coefficients (r). RESULTS center dot A total of 338 agreed to participate, representing 76% of those who were invited. center dot Younger patients experienced less uncertainty (r= 0.20, P < 0.001), yet reported greater perception of danger (r=0.12; P= 0.03) concerning their previously treated prostate cancer. center dot African-American patients showed greater uncertainty than other ethnic groups (P= 0.005) but did not have a greater perception of danger (P= 0.36). center dot Education played a major role in uncertainty; patients with lower levels of education tended to report higher degrees of uncertainty (r=0.25; P < 0.001). center dot There was a mild to moderate general association between the three outcomes. A greater sense of uncertainty was associated with a greater perception of danger (r= 0.34, P < 0.001), and as danger and uncertainty increased, satisfaction with treatment outcome tended to decrease (r was between 0.30 and 0.34, P < 0.001). CONCLUSIONS center dot Results suggest that possible disparities related to patient racial background and education may exist in the perception of cancer-related uncertainty. center dot Racial and educational disparities, coupled with a mild to moderate association of uncertainty or danger perception and overall outcome satisfaction, suggest an unmet need for healthcare and nursing services for men undergoing treatment for prostate cancer. C1 [Kazer, Meredith Wallace; Regan, Meredith] Fairfield Univ, Sch Nursing, Fairfield, CT 06430 USA. [Bailey, Donald E., Jr.] Duke Univ, Sch Nursing, Durham, NC USA. [Chipman, Jonathan] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Psutka, Sarah P.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Crociani, Catrina; Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Urol, Boston, MA 02215 USA. [Crociani, Catrina; Sanda, Martin G.] Harvard Univ, Sch Med, Boston, MA USA. [Hardy, Jill; Hembroff, Larry] Michigan State Univ, Off Survey Res, E Lansing, MI 48824 USA. [Dunn, Rodney L.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. RP Kazer, MW (reprint author), Fairfield Univ, Fairfield, CT 06824 USA. EM mkazer@fairfield.edu RI Sanda, Martin/B-2023-2015 FU NIH [R01 CA 95662, 1RC1CA146596] FX NIH R01 CA 95662; NIH 1RC1CA146596. NR 18 TC 7 Z9 7 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2013 VL 111 IS 3B BP E84 EP E91 DI 10.1111/j.1464-410X.2012.11439.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 099SU UT WOS:000315642700011 PM 22985348 ER PT J AU Lee, RS Roberts, CWM AF Lee, Ryan S. Roberts, Charles W. M. TI Rhabdoid Tumors: An Initial Clue to the Role of Chromatin Remodeling in Cancer SO BRAIN PATHOLOGY LA English DT Article DE AT/RT; cancer genomics; epigenetics; rhabdoid; SMARCB1; SWI/SNF ID CENTRAL-NERVOUS-SYSTEM; ATYPICAL TERATOID/RHABDOID TUMORS; IDENTIFIES FREQUENT MUTATION; SUPPRESSOR SNF5 LEADS; SOMATIC MUTATIONS; CELL CARCINOMA; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; GENOMIC INSTABILITY; LUNG ADENOCARCINOMA AB The discovery of biallelic, inactivating SMARCB1 mutations in rhabdoid tumors (RTs) over a decade ago represented the first recognized link between chromatin remodeling and tumor suppression. SMARCB1 is a core subunit of the SWI/SNF chromatin remodeling complex, and the recent emergence of frequent mutations in genes that encode subunits of this complex across a wide variety of cancers suggests that perturbation of this chromatin remodeling complex constitutes a key driver of cancer formation. Despite the highly aggressive nature of RTs, they are genetically simple cancers that appear to lack chromosomal instability and contain very few mutations. Indeed, the mutation rate in RTs is among the lowest of all cancers sequenced, with loss of SMARCB1 as essentially the sole recurrent event. Given the genetic simplicity of this disease, understanding the chromatin dysregulation caused by SMARCB1 loss may provide more general insight into how epigenetic alterations can contribute to oncogenic transformation and may reveal opportunities for targeted therapy not only of RT but also the variety of other SWI/SNF mutant cancers. C1 [Lee, Ryan S.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Lee, Ryan S.; Roberts, Charles W. M.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Lee, Ryan S.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Charles_Roberts@dfci.harvard.edu NR 87 TC 13 Z9 13 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD MAR PY 2013 VL 23 IS 2 BP 200 EP 205 DI 10.1111/bpa.12021 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 096MD UT WOS:000315407300010 PM 23432645 ER PT J AU Hebron, E Hope, C Kim, J Jensen, JL Flanagan, C Bhatia, N Maroulakou, I Mitsiades, C Miyamoto, S Callander, N Hematti, P Asimakopoulos, F AF Hebron, Ellen Hope, Chelsea Kim, Jaehyup Jensen, Jeffrey L. Flanagan, Claire Bhatia, Neehar Maroulakou, Ioanna Mitsiades, Constantine Miyamoto, Shigeki Callander, Natalie Hematti, Peiman Asimakopoulos, Fotis TI MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myeloma; bone marrow pathology; macrophages ID MULTIPLE-MYELOMA; MACROPHAGES; PATHWAY; INDUCTION; ALPHA AB Benefit from cytotoxic therapy in myeloma may be limited by the persistence of residual tumour cells within protective niches. We have previously shown that monocytes/macrophages acquire a proinflammatory transcriptional profile in the myeloma microenvironment. Here we report constitutive activation of MAP3K8 kinase-dependent pathways that regulate the magnitude and extent of inflammatory activity of monocytes/macrophages within myeloma niches. In myeloma tumour cells, MAP3K8 acts as mitogen-induced MAP3K in mitosis and is required for TNF-mediated ERK activation. Pharmacological MAP3K8 inhibition results in dose-dependent, tumour cell-autonomous apoptosis despite contact with primary stroma. MAP3K8 blockade may disrupt crucial macrophage-tumour cell interactions within myeloma niches. C1 [Hebron, Ellen; Hope, Chelsea; Kim, Jaehyup; Jensen, Jeffrey L.; Flanagan, Claire; Bhatia, Neehar; Callander, Natalie; Hematti, Peiman; Asimakopoulos, Fotis] Univ Wisconsin, Dept Med, Madison Sch Med & Publ Hlth, Div Hematol Oncol, Madison, WI USA. [Hebron, Ellen; Hope, Chelsea; Kim, Jaehyup; Jensen, Jeffrey L.; Flanagan, Claire; Bhatia, Neehar; Miyamoto, Shigeki; Callander, Natalie; Hematti, Peiman; Asimakopoulos, Fotis] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Maroulakou, Ioanna] Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece. [Mitsiades, Constantine] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Miyamoto, Shigeki] Univ Wisconsin, Dept Oncol, Madison Sch Med & Publ Hlth, Madison, WI USA. RP Asimakopoulos, F (reprint author), 1111 Highland Ave,WIMR 4031, Madison, WI 53705 USA. EM fasimako@medicine.wisc.edu RI Kim, Jaehyup/N-5800-2015 OI Kim, Jaehyup/0000-0003-0373-5080 FU Leukemia Research Foundation; Kirschstein National Research Service Award [T32 HL007899]; Clinical and Translational Science Award (CTSA) programme through the National Center for Research Resources (NCRR) [1UL1RR025011]; National Center for Advancing Translational Sciences (NCATS) [9U54TR000021]; NHLBI - NIH [K08 HL081076]; UWCCC Trillium Fund for Multiple Myeloma Research; UW Horace Collins Research Fund; Wisconsin Alumni Research Foundation through the UW Graduate School; UW Carbone Cancer Center [P30 CA014520]; UW-Madison School of Medicine and Public Health FX We thank Dr. Emery Bresnick for critical review of the manuscript and the Bresnick laboratory members for valuable help with the experiments. FA is the recipient of a Leukemia Research Foundation New Investigator Award. CH is the recipient of a Kirschstein National Research Service Award (T32 HL007899-Hematology in Training-PI, John Sheehan). JLJ is the recipient of a TL1 trainee award from the Clinical and Translational Science Award (CTSA) programme, previously through the National Center for Research Resources (NCRR) grant 1UL1RR025011, and now by the National Center for Advancing Translational Sciences (NCATS), grant 9U54TR000021 (PI, Marc Drezner). PH is recipient of NHLBI - NIH grant K08 HL081076. This work was supported in part by funds from the UWCCC Trillium Fund for Multiple Myeloma Research, the UW Horace Collins Research Fund, the Wisconsin Alumni Research Foundation through the UW Graduate School, the UW Carbone Cancer Center (Core Grant P30 CA014520) and the UW-Madison School of Medicine and Public Health. NR 15 TC 3 Z9 3 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2013 VL 160 IS 6 BP 779 EP 784 DI 10.1111/bjh.12175 PG 6 WC Hematology SC Hematology GA 100ZF UT WOS:000315743700007 PM 23252623 ER PT J AU Wender, R Fontham, ETH Barrera, E Colditz, GA Church, TR Ettinger, DS Etzioni, R Flowers, CR Gazelle, GS Kelsey, DK LaMonte, SJ Michaelson, JS Oeffinger, KC Shih, YCT Sullivan, DC Travis, W Walter, L Wolf, AMD Brawley, OW Smith, RA AF Wender, Richard Fontham, Elizabeth T. H. Barrera, Ermilo, Jr. Colditz, Graham A. Church, Timothy R. Ettinger, David S. Etzioni, Ruth Flowers, Christopher R. Gazelle, G. Scott Kelsey, Douglas K. LaMonte, Samuel J. Michaelson, James S. Oeffinger, Kevin C. Shih, Ya-Chen Tina Sullivan, Daniel C. Travis, William Walter, Louise Wolf, Andrew M. D. Brawley, Otis W. Smith, Robert A. TI American Cancer Society Lung Cancer Screening Guidelines SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article DE humans; lung neoplasms; mortality; radiography; radiation dosage; randomized controlled trials as topic; risk; risk reduction behavior; x-ray; computed tomography; adverse effects; lung cancer screening ID LOW-DOSE CT; COMPUTED-TOMOGRAPHY SCANS; SPIRAL CT; FOLLOW-UP; FORMER SMOKERS; DANTE TRIAL; MORTALITY; SMOKING; RISK; PROGRAM AB Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. CA Cancer J Clin 2013;63:106-117. (C) 2013 American Cancer Society. C1 [Wender, Richard] Thomas Jefferson Univ, Coll Med, Dept Family & Community Med, Philadelphia, PA 19107 USA. [Fontham, Elizabeth T. H.] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA. [Barrera, Ermilo, Jr.] NorthShore Univ Hlth Syst, Dept Surg, Evanston, IL USA. [Barrera, Ermilo, Jr.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Inst Publ Hlth, St Louis, MO USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Dept Environm Hlth Sci, Masonic Canc Ctr, Minneapolis, MN USA. [Ettinger, David S.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [Etzioni, Ruth] Univ Washington, Sch Publ Hlth, Fred Hutchinson Canc Res Ctr, Hlth Serv, Seattle, WA 98195 USA. [Flowers, Christopher R.] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Ctr Comprehens Informat,Winship Canc Inst, Atlanta, GA USA. [Gazelle, G. Scott] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Kelsey, Douglas K.] US Med Div Neurosci, Lilly Res Labs, Indianapolis, IN USA. [LaMonte, Samuel J.] Louisiana State Univ, Sch Med, Dept Otolaryngol & Head & Neck Surg, Shreveport, LA USA. [Michaelson, James S.] Massachusetts Gen Hosp, Lab Quantitat Med, Cambridge, MA USA. [Michaelson, James S.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Adult Long Term Follow Up Program, New York, NY 10021 USA. [Shih, Ya-Chen Tina] Univ Chicago, Dept Med, Sect Hosp Med, Chicago, IL 60637 USA. [Shih, Ya-Chen Tina] Univ Chicago, Program Econ Canc, Chicago, IL 60637 USA. [Sullivan, Daniel C.] Duke Univ, Med Ctr, Dept Radiol, Chapel Hill, NC USA. [Travis, William] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Walter, Louise] Univ Calif San Francisco, Dept Med, Div Geriatr, Geriatr Res Program, San Francisco, CA USA. [Wolf, Andrew M. D.] Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA USA. [Brawley, Otis W.] Amer Canc Soc, Atlanta, GA 30303 USA. [Smith, Robert A.] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA. RP Smith, RA (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St,Suite 600, Atlanta, GA 30303 USA. EM robert.smith@cancer.org RI Flowers, Christopher/F-1953-2010; Colditz, Graham/A-3963-2009; OI Flowers, Christopher/0000-0002-9524-3990; Colditz, Graham/0000-0002-7307-0291; Church, Timothy R./0000-0003-3292-5035 FU Celgene Corporation; Spectrum; Seattle Genetics, Inc; OptumRx; Clinical Care Options; Education Concepts Group FX Dr. Flowers has received consulting fees from Celgene Corporation; Spectrum; Seattle Genetics, Inc; OptumRx; Clinical Care Options; and Education Concepts Group. He has performed contracted research for Millennium Pharmaceuticals, Celgene Corporation, Spectrum, Gilead Pharmaceuticals, and Janssen Pharmaceuticals. Dr. Gazelle is a consultant to GE Healthcare. His work for GE Healthcare is not directly related to this article. Dr. Kelsey is employed by Eli Lilly and Company. NR 55 TC 197 Z9 210 U1 5 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAR-APR PY 2013 VL 63 IS 2 BP 107 EP 117 DI 10.3322/caac.21172 PG 11 WC Oncology SC Oncology GA 099TZ UT WOS:000315646500004 PM 23315954 ER PT J AU Abel, GA Chen, K Taback, N Hassett, MJ Schrag, D Weeks, JC AF Abel, Gregory A. Chen, Kun Taback, Nathan Hassett, Michael J. Schrag, Deborah Weeks, Jane C. TI Impact of oncology-related direct-to-consumer advertising Association With Appropriate and Inappropriate Prescriptions SO CANCER LA English DT Article; Proceedings Paper CT CTRC-AACR CY FEB 19, 2013 CL San Antonio, TX DE direct-to-consumer advertising; health services research; breast cancer; outcomes; population sciences ID POSITIVE BREAST-CANCER; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; MENOPAUSAL STATUS; AMERICAN-SOCIETY; ADJUVANT THERAPY; NATIONAL TRENDS; TRIAL; TAMOXIFEN; PROMOTION AB BACKGROUND: Little is known about the impact of direct-to-consumer advertising (DTCA) on appropriate versus inappropriate prescribing. Aromatase inhibitor (AI) therapy for breast cancer provides an ideal paradigm for studying this issue, because AIs have been the focus of substantial DTCA, and because they should only be used in postmenopausal women, age can serve as a simple surrogate marker of appropriateness. METHODS: Data regarding national DTCA spending for the AIs were obtained from TNS Multimedia; hormonal therapy prescription data were obtained from IMS Health. Time series analyses were performed to characterize the association between monthly changes in DTCA spending for the AIs and monthly changes in the proportion of all new hormonal therapy prescriptions represented by the AIs from October 2005 to September 2007. Analyses were stratified by age, considering prescriptions for women 40 (likely premenopausal) to be inappropriate and those for women > 60 (likely postmenopausal) to be appropriate. RESULTS: Monthly dollars spent on AI-associated DTCA varied considerably ($118,600 to $22,019,660). Time series analysis revealed that for every million dollars spent on DTCA for the AIs, there was an associated increase 3 months later in the new AI prescription proportion of 0.15% for all ages (P < .0001) and 0.18% for those > 60 years (P < .0001), but no significant change for those 40 at any time from 0 to 6 months. CONCLUSIONS: DTCA for the AIs was associated with increases in appropriate prescriptions with no significant effect on inappropriate prescriptions, suggesting that DTCA may not foster inappropriate medication use for certain drug classes. Cancer 2013. (c) 2012 American Cancer Society. C1 [Abel, Gregory A.; Chen, Kun; Taback, Nathan; Hassett, Michael J.; Schrag, Deborah; Weeks, Jane C.] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02215 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave,Dana 1106, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu FU American Society for Clinical Oncology Conquer Cancer Foundation FX This work was partially funded by an American Society for Clinical Oncology Conquer Cancer Foundation Career Development Award. NR 43 TC 5 Z9 5 U1 1 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 MAR 1 PY 2013 VL 119 IS 5 BP 1065 EP 1072 DI 10.1002/cncr.27814 PG 8 WC Oncology SC Oncology GA 093TD UT WOS:000315214000021 PM 23132702 ER PT J AU Swirski, FK Robbins, CS AF Swirski, Filip K. Robbins, Clinton S. TI Neutrophils Usher Monocytes Into Sites of Inflammation SO CIRCULATION RESEARCH LA English DT Editorial Material DE cathelicidin; chemokine; inflammation; monocyte; neutrophil; recruitment ID ATHEROSCLEROSIS; MICE C1 [Swirski, Filip K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Robbins, Clinton S.] Univ Toronto, Toronto Gen Res Inst, Heart & Stroke Richard Lewar Ctr Excellence Cardi, Toronto, ON M5G 1L7, Canada. RP Swirski, FK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Simches Res Bldg,Room 8-226,185 Cambridge St, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu; crobbins@uhnres.utoronto.ca FU NHLBI NIH HHS [R01HL095612] NR 8 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 1 PY 2013 VL 112 IS 5 BP 744 EP 745 DI 10.1161/CIRCRESAHA.113.300867 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 098YV UT WOS:000315585900002 PM 23449542 ER PT J AU Majmudar, MD Yoo, J Keliher, EJ Truelove, JJ Iwamoto, Y Sena, B Dutta, P Borodovsky, A Fitzgerald, K Di Carli, MF Libby, P Anderson, DG Swirski, FK Weissleder, R Nahrendorf, M AF Majmudar, Maulik D. Yoo, Jeongsoo Keliher, Edmund J. Truelove, Jessica J. Iwamoto, Yoshiko Sena, Brena Dutta, Partha Borodovsky, Anna Fitzgerald, Kevin Di Carli, Marcelo F. Libby, Peter Anderson, Daniel G. Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias TI Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques SO CIRCULATION RESEARCH LA English DT Article DE atherosclerosis; inflammation; macrophage; molecular imaging; nanoparticles; PET/MRI ID POSITRON-EMISSION-TOMOGRAPHY; INFLAMMATION; MICE; MONOCYTES; DISEASE; MYOCARDIUM; CHEMOKINES AB Rationale: Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocytes and macrophages could serve as a biomarker of disease progression and therapeutic intervention. Objective: To noninvasively assess plaque inflammation with dextran nanoparticle (DNP)-facilitated hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Methods and Results: Using clinically approved building blocks, we systematically developed 13-nm polymeric nanoparticles consisting of cross-linked short chain dextrans, which were modified with desferoxamine for zirconium-89 radiolabeling (Zr-89-DNP) and a near-infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in monocytes and macrophages (76.7%) and lower signal originating from other leukocytes, such as neutrophils and lymphocytes (11.8% and 0.7%, P<0.05 versus monocytes and macrophages). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of Zr-89-DNP in the aortic root of apolipoprotein E knock out (ApoE(-/-)) mice (standard uptake value, ApoE(-/-) mice versus wild-type controls, 1.9+/-0.28 versus 1.3+/-0.03; P<0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor C-C chemokine receptor type 2 with short-interfering RNA decreased Zr-89-DNP plaque signal (P<0.05) and inflammatory gene expression (P<0.05). Conclusions: Hybrid PET/MRI with a 13-nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy. (Circ Res. 2013;122:755-761.) C1 [Majmudar, Maulik D.; Yoo, Jeongsoo; Keliher, Edmund J.; Truelove, Jessica J.; Iwamoto, Yoshiko; Sena, Brena; Dutta, Partha; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Majmudar, Maulik D.; Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Yoo, Jeongsoo] Kyungpook Natl Univ, Sch Med, Dept Mol Med, Taegu, South Korea. [Borodovsky, Anna; Fitzgerald, Kevin] Alnylam Pharmaceut, Cambridge, MA USA. [Di Carli, Marcelo F.] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Anderson, Daniel G.] MIT, Div Hlth Sci Technol, Cambridge, MA 02139 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268201000044C, R01-HL096576, R01-HL095629, T32-HL094301] FX This project has been funded in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (HHSN268201000044C, R01-HL096576, R01-HL095629, and T32-HL094301). NR 22 TC 58 Z9 59 U1 4 U2 60 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 1 PY 2013 VL 112 IS 5 BP 755 EP 761 DI 10.1161/CIRCRESAHA.111.300576 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 098YV UT WOS:000315585900006 PM 23300273 ER PT J AU Hayes, P Gilmour, J von Lieven, A Gill, D Clark, L Kopycinski, J Cheeseman, H Chung, A Alter, G Dally, L Zachariah, D Lombardo, A Ackland, J Sayeed, E Jackson, A Boffito, M Gazzard, B Fast, PE Cox, JH Laufer, D AF Hayes, Peter Gilmour, Jill von Lieven, Andrea Gill, Dilbinder Clark, Lorna Kopycinski, Jakub Cheeseman, Hannah Chung, Amy Alter, Galit Dally, Len Zachariah, Devika Lombardo, Angela Ackland, James Sayeed, Eddy Jackson, Akil Boffito, Marta Gazzard, Brian Fast, Patricia E. Cox, Josephine H. Laufer, Dagna TI Safety and Immunogenicity of DNA Prime and Modified Vaccinia Ankara Virus-HIV Subtype C Vaccine Boost in Healthy Adults SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; NEUTRALIZING ANTIBODY-RESPONSE; IMMUNE-RESPONSES; PHASE-1 SAFETY; CANDIDATE VACCINE; CLINICAL-TRIALS; EFFICACY TRIALS; RHESUS-MONKEYS; TYPE-1; MVA AB A randomized, double-blind, placebo-controlled phase I trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of 3 doses of DNA vaccine (Advax) plus 1 dose of recombinant modified vaccinia virus Ankara (MVA) (TBC-M4) or 3 doses of TBC-M4 alone (groups A and B, respectively). Both vaccine regimens were found to be safe and well tolerated. Gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assay responses were detected in 1/10 (10%) individuals in group A after three Advax primes and in 9/9 individuals (100%) after the MVA boost. In group B, IFN-gamma ELISPOT responses were detected in 6/12 (50%) and 7/11 (64%) individuals after the second and third MVA vaccinations, respectively. Responses to all vaccine components, but predominantly to Env, were seen. The breadth and magnitude of the T cell response and viral inhibition were greater in group A than in group B, indicating that the quality of the T-cell response was enhanced by the DNA prime. Intracellular cytokine staining indicated that the T-cell responses were polyfunctional but were skewed toward Env with a CD4(+) phenotype. At 2 weeks after the last vaccination, HIV-specific antibody responses were detected in all (100%) group B and 1/11 (9.1%) group A vaccinees. Vaccinia virus-specific responses were detected in all (100%) group B and 2/11 (18.2%) group A vaccinees. In conclusion, HIV-specific T-cell responses were seen in the majority of volunteers in groups A and B but with a trend toward greater quality of the T-cell response in group A. Antibody responses were better in group B than in group A. C1 [Hayes, Peter; Gilmour, Jill; Gill, Dilbinder; Clark, Lorna; Kopycinski, Jakub; Cheeseman, Hannah; Cox, Josephine H.] Univ London Imperial Coll Sci Technol & Med, IAVI Human Immunol Lab, London, England. [von Lieven, Andrea; Zachariah, Devika; Lombardo, Angela; Sayeed, Eddy; Fast, Patricia E.; Laufer, Dagna] Int AIDS Vaccine Initiat, New York, NY USA. [Chung, Amy; Alter, Galit] MIT, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA. [Chung, Amy; Alter, Galit] Harvard Univ, Charlestown, MA USA. [Dally, Len] EMMES Corp, Rockville, MD USA. [Ackland, James] Global BioSolut, Melbourne, Vic, Australia. [Jackson, Akil; Boffito, Marta; Gazzard, Brian] Chelsea & Westminster Hosp, St Stephens Ctr, London, England. RP Cox, JH (reprint author), Univ London Imperial Coll Sci Technol & Med, IAVI Human Immunol Lab, London, England. EM jcox@iavi.org OI Chung, Amy/0000-0003-0020-9704 FU International AIDS Vaccine Initiative; United States Agency for International Development (USAID) [GPO-A-00-06-00006-00]; Government of Canada; Government of Denmark; Government of Ireland; Government of The Netherlands; Government of Norway; Government of Sweden; Government of United Kingdom; Basque Autonomous Government; European Union; Bill & Melinda Gates Foundation; National Institutes of Health [R01AI080289]; American-Australian Association (AAA); National Health and Medical Research Center [APP1036470] FX This study was sponsored by the International AIDS Vaccine Initiative and funded by its donors, including the United States Agency for International Development (USAID Cooperative Agreement Number GPO-A-00-06-00006-00), the Governments of Canada, Denmark, Ireland, The Netherlands, Norway, Sweden, and the United Kingdom, the Basque Autonomous Government, the European Union, and the Bill & Melinda Gates Foundation. The Luminex antibody assays were conducted at the Ragon Institute and supported by the National Institutes of Health (R01AI080289), the American-Australian Association (AAA), and National Health and Medical Research Center (APP1036470). NR 61 TC 10 Z9 10 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAR PY 2013 VL 20 IS 3 BP 397 EP 408 DI 10.1128/CVI.00637-12 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 096NL UT WOS:000315411100010 PM 23345581 ER PT J AU Lu, WD Rosenthal, DS AF Lu, Weidong Rosenthal, David S. TI Acupuncture for Cancer Pain and Related Symptoms SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Acupuncture; Acupuncture protocol; Aromatase inhibitor-associated joint pain; Cancer pain; Chemotherapy-induced neuropathy; Clinical practice; Clinical trials; Electroacupuncture; Evidence; Neck dissection-related pain; Oncology acupuncture; Opioid-induced constipation; Opioid-induced pruritus; Postoperative cancer pain; Postoperative nausea and vomiting; Postsurgical gastroparesis syndrome ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; INTEGRATIVE ONCOLOGY; COMPLEMENTARY THERAPIES; POSTOPERATIVE NAUSEA; RAT MODEL; ELECTROACUPUNCTURE; MANAGEMENT; ANALGESIA; PLACEBO AB Cancer pain is one of most prevalent symptoms in patients with cancer. Acupuncture and related techniques have been suggested for the management of cancer pain. The National Comprehensive Cancer Network guidelines for adult cancer pain recommends acupuncture, as one of several integrative interventions, in conjunction with pharmacologic intervention as needed. This review presents the latest available evidence regarding the use of acupuncture for cancer pain. It also provides "actionable" acupuncture protocols for specific cancer pain conditions and related symptoms in order to provide more clinically relevant solutions for clinicians and cancer patients with pain. These conditions include postoperative cancer pain, postoperative nausea and vomiting, postsurgical gastroparesis syndrome, opioid-induced constipation, opioid-induced pruritus, chemotherapy-induced neuropathy, aromatase inhibitor-associated joint pain, and neck dissection-related pain and dysfunction. C1 [Lu, Weidong; Rosenthal, David S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. RP Lu, WD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, 44 Binney St, Boston, MA 02115 USA. EM weidong_lu@dfci.harvard.edu RI Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 FU National Center for Complementary and Alternative Medicine (NCCAM) [1K01 AT004415] FX This study was supported by grant #1K01 AT004415 from the National Center for Complementary and Alternative Medicine (NCCAM). NR 54 TC 11 Z9 11 U1 2 U2 43 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD MAR PY 2013 VL 17 IS 3 DI 10.1007/s11916-013-0321-3 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 099OD UT WOS:000315630200006 PM 23338773 ER PT J AU Guner-Ataman, B Paffett-Lugassy, N Adams, MS Nevis, KR Jahangiri, L Obregon, P Kikuchi, K Poss, KD Burns, CE Burns, CG AF Guner-Ataman, Burcu Paffett-Lugassy, Noelle Adams, Meghan S. Nevis, Kathleen R. Jahangiri, Leila Obregon, Pablo Kikuchi, Kazu Poss, Kenneth D. Burns, Caroline E. Burns, C. Geoffrey TI Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function SO DEVELOPMENT LA English DT Article DE Gata4; Heart development; Lineage tracing; Nkx2.5; Second heart field; Zebrafish ID HOMEOBOX GENE NKX2-5; CARDIAC DEVELOPMENT; ARTERIAL POLE; CARDIOMYOCYTE DIFFERENTIATION; RESTRICTED EXPRESSION; DISTINCT PHASES; OUTFLOW TRACT; SMOOTH-MUSCLE; DISEASE; CELLS AB Second heart field (SHF) progenitors perform essential functions during mammalian cardiogenesis. We recently identified a population of cardiac progenitor cells (CPCs) in zebrafish expressing latent TGF beta-binding protein 3 (ltbp3) that exhibits several defining characteristics of the anterior SHF in mammals. However, ltbp3 transcripts are conspicuously absent in anterior lateral plate mesoderm (ALPM), where SHF progenitors are specified in higher vertebrates. Instead, ltbp3 expression initiates at the arterial pole of the developing heart tube. Because the mechanisms of cardiac development are conserved evolutionarily, we hypothesized that zebrafish SHF specification also occurs in the ALPM. To test this hypothesis, we Cre/loxP lineage traced gata4(+) and nkx2.5(+) ALPM populations predicted to contain SHF progenitors, based on evolutionary conservation of ALPM patterning. Traced cells were identified in SHF-derived distal ventricular myocardium and in three lineages in the outflow tract (OFT). We confirmed the extent of contributions made by ALPM nkx2.5+ cells using Kaede photoconversion. Taken together, these data demonstrate that, as in higher vertebrates, zebrafish SHF progenitors are specified within the ALPM and express nkx2.5. Furthermore, we tested the hypothesis that Nkx2.5 plays a conserved and essential role during zebrafish SHF development. Embryos injected with an nkx2.5 morpholino exhibited SHF phenotypes caused by compromised progenitor cell proliferation. Co-injecting low doses of nkx2.5 and ltbp3 morpholinos revealed a genetic interaction between these factors. Taken together, our data highlight two conserved features of zebrafish SHF development, reveal a novel genetic relationship between nkx2.5 and ltbp3, and underscore the utility of this model organism for deciphering SHF biology. C1 [Guner-Ataman, Burcu; Paffett-Lugassy, Noelle; Adams, Meghan S.; Nevis, Kathleen R.; Jahangiri, Leila; Obregon, Pablo; Burns, Caroline E.; Burns, C. Geoffrey] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Guner-Ataman, Burcu; Paffett-Lugassy, Noelle; Adams, Meghan S.; Nevis, Kathleen R.; Jahangiri, Leila; Obregon, Pablo; Burns, Caroline E.; Burns, C. Geoffrey] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Paffett-Lugassy, Noelle; Burns, Caroline E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Kikuchi, Kazu; Poss, Kenneth D.] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA. [Kikuchi, Kazu; Poss, Kenneth D.] Duke Univ, Howard Hughes Med Inst, Durham, NC 27710 USA. RP Burns, CE (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM cburns6@partners.org; gburns@cvrc.mgh.harvard.edu RI Kikuchi, Kazu/A-4097-2017 OI Kikuchi, Kazu/0000-0002-4681-4275 FU American Heart Association (AHA) [10POST4170037, 10GRNT4270021]; Harvard Stem Cell Institute (HSCI) [5T32HL087735]; Cell and Molecular Training Grant For Cardiovascular Biology [5T32HL007208]; National Research Service Award from the National Heart, Lung and Blood Institute (NHLBI) [5F32HL110627]; NHLBI [5R01HL111179, 5R01HL096816]; March of Dimes Foundation [1-FY12-467] FX B.G.-A. was funded by an American Heart Association (AHA) Post-Doctoral Fellowship [10POST4170037], N.P.-L. was funded by the Harvard Stem Cell Institute (HSCI) Training Program for Post-Doctoral Fellows [5T32HL087735], M.S.A. was funded by the Cell and Molecular Training Grant For Cardiovascular Biology [5T32HL007208], K.R.N. was funded by a National Research Service Award [5F32HL110627] from the National Heart, Lung and Blood Institute (NHLBI). This work was funded by awards from the NHLBI [5R01HL111179], the March of Dimes Foundation [1-FY12-467] and the HSCI (Seed Grant and Young Investigator Award) to C.E.B.; and by NHLBI [5R01HL096816], AHA [Grant in Aid number 10GRNT4270021] and HSCI (Seed Grant) awards to C.G.B. Deposited in PMC for release after 12 months. NR 63 TC 23 Z9 24 U1 1 U2 17 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 2013 VL 140 IS 6 BP 1353 EP 1363 DI 10.1242/dev.088351 PG 11 WC Developmental Biology SC Developmental Biology GA 097AH UT WOS:000315445800021 PM 23444361 ER PT J AU Tanigaki, K Vongpatanasin, W Barrera, JA Atochin, DN Huang, PL Bonvini, E Shaul, PW Mineo, C AF Tanigaki, Keiji Vongpatanasin, Wanpen Barrera, Jose A. Atochin, Dmitriy N. Huang, Paul L. Bonvini, Ezio Shaul, Philip W. Mineo, Chieko TI C-Reactive Protein Causes Insulin Resistance in Mice Through Fc gamma Receptor IIB-Mediated Inhibition of Skeletal Muscle Glucose Delivery SO DIABETES LA English DT Article ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL NO SYNTHASE; ADIPOSE-TISSUE; METABOLIC SYNDROME; DIABETES-MELLITUS; TRANSGENIC MICE; IN-VIVO; INFLAMMATION; OBESITY; HYPERTENSION AB Elevations in C-reactive protein (CRP) are associated with an increased risk of insulin resistance. Whether CRP plays a causal role is unknown. Here we show that CRP transgenic mice and wild-type mice administered recombinant CRP are insulin resistant. Mice lacking the inhibitory Fc gamma receptor IIB (Fc gamma RIIB) are protected from CRP-induced insulin resistance, and immunohistochemistry reveals that Fc gamma RIIB is expressed in skeletal muscle microvascular endothelium and is absent in skeletal muscle myocytes, adipocytes, and hepatocytes. The primary mechanism in glucose homeostasis disrupted by CRP is skeletal muscle glucose delivery, and CRP attenuates insulin-induced skeletal muscle blood flow. CRP does not impair skeletal muscle glucose delivery in Fc gamma RIIB-/- mice or in endothelial nitric oxide synthase knock-in mice with phosphomimetic modification of Ser1176, which is normally phosphorylated by insulin signaling to stimulate nitric oxide-mediated skeletal muscle blood flow and glucose delivery and is dephosphorylated by CRP/Fc gamma RIIB. Thus, CRP causes insulin resistance in mice through Fc gamma RIIB-mediated inhibition of skeletal muscle glucose delivery. Diabetes 62:721-731, 2013 C1 [Tanigaki, Keiji; Barrera, Jose A.; Shaul, Philip W.; Mineo, Chieko] Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Pulm & Vasc Biol, Dallas, TX 75390 USA. [Vongpatanasin, Wanpen] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Hypertens Sect, Dallas, TX 75390 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. [Bonvini, Ezio] MacroGenics Inc, Rockville, MD USA. RP Mineo, C (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Pulm & Vasc Biol, Dallas, TX 75390 USA. EM chieko.mineo@utsouthwestern.edu RI Atochin, Dmitriy/Q-3150-2016 FU American Diabetes Association [1-10-BS-124]; National Institutes of Health [HL-75473, NS-33335]; Donald W. Reynolds Cardiovascular Clinical Research Center; O'Brien Kidney Center; American Heart Association Scientist Development; Children's Medical Center of Dallas Research Foundation; [0835344N] FX This work was supported by the American Diabetes Association Grant 1-10-BS-124 (C.M.), National Institutes of Health Grants HL-75473 (P.W.S.) and NS-33335 (P.L.H.), the Donald W. Reynolds Cardiovascular Clinical Research Center (W.V.), the O'Brien Kidney Center (W.V.), the American Heart Association Scientist Development Grant 0835344N (D.N.A.), and the Children's Medical Center of Dallas Research Foundation (P.W.S.). NR 46 TC 13 Z9 15 U1 2 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2013 VL 62 IS 3 BP 721 EP 731 DI 10.2337/db12-0133 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 098NQ UT WOS:000315556400016 PM 23069625 ER PT J AU Qatanani, M Tan, YJ Dobrin, R Greenawalt, DM Hu, GH Zhao, WQ Olefsky, JM Sears, DD Kaplan, LM Kemp, DM AF Qatanani, Mohammed Tan, Yejun Dobrin, Radu Greenawalt, Danielle M. Hu, Guanghui Zhao, Wenqing Olefsky, Jerrold M. Sears, Dorothy D. Kaplan, Lee M. Kemp, Daniel M. TI Inverse Regulation of Inflammation and Mitochondrial Function in Adipose Tissue Defines Extreme Insulin Sensitivity in Morbidly Obese Patients SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; METABOLIC DISEASE; RESISTANCE; MECHANISMS; EPIDEMIC; PROFILE; CELLS; FAT; INDIVIDUALS; HOMEOSTASIS AB Obesity is associated with insulin resistance, a major risk factor for type 2 diabetes and cardiovascular disease. However, not all obese individuals are insulin resistant, which confounds our understanding of the mechanistic link between these conditions. We conducted transcriptome analyses on 835 obese subjects with mean BMI of 48.8, on which we have previously reported genetic associations of gene expression. Here, we selected similar to 320 nordiabetic (HbA(1c) <7.0) subjects and further stratified the cohort into insulin-resistant versus insulin-sensitive subgroups based on homeostasis model assessment-insulin resistance. An unsupervised informatics analysis revealed that immune response and inflammation-related genes were significantly downregulated in the omental adipose tissue of obese individuals with extreme insulin sensitivity and, to a much lesser extent, in subcutaneous adipose tissue. In contrast, genes related to beta-oxidation and the citric acid cycle were relatively overexpressed in adipose of insulin-sensitive patients. These observations were verified by querying an independent cohort of our published dataset of 37 subjects whose subcutaneous adipose tissue was sampled before and after treatment with thiazolidinediones. Whereas the immune response and inflammation pathway genes were downregulated by thiazolidinedione treatment, beta-oxidation and citric acid cycle genes were upregulated. This work highlights the critical role that mental adipose inflammatory pathways might play in the pathophysiology of insulin resistance, independent of body weight. Diabetes 62:855-863, 2013 C1 [Qatanani, Mohammed; Tan, Yejun; Dobrin, Radu; Greenawalt, Danielle M.; Hu, Guanghui; Zhao, Wenqing; Kemp, Daniel M.] Merck Res Labs, Discovery & Preclin Sci, Rahway, NJ 07055 USA. [Qatanani, Mohammed; Kemp, Daniel M.] Merck Res Labs, Diabet & Endocrinol, Rahway, NJ USA. [Tan, Yejun; Dobrin, Radu; Greenawalt, Danielle M.; Hu, Guanghui; Zhao, Wenqing] Merck Res Labs, Informat & Anal, Rahway, NJ USA. [Olefsky, Jerrold M.; Sears, Dorothy D.] Univ Calif San Diego, Dept Med, Div Endocrinol & Metab, La Jolla, CA 92093 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Metab Lab, Boston, MA 02114 USA. [Kaplan, Lee M.] Harvard Univ, Sch Med, Boston, MA USA. RP Kemp, DM (reprint author), Merck Res Labs, Discovery & Preclin Sci, Rahway, NJ 07055 USA. EM daniel_kemp@merck.com OI Dobrin, Radu/0000-0002-3336-0091 NR 47 TC 21 Z9 21 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2013 VL 62 IS 3 BP 855 EP 863 DI 10.2337/db12-0399 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 098NQ UT WOS:000315556400029 PM 23223024 ER PT J AU Lee, KY Russell, SJ Ussar, S Boucher, J Vernochet, C Mori, MA Smyth, G Rourk, M Cederquist, C Rosen, ED Kahn, BB Kahn, CR AF Lee, Kevin Y. Russell, Steven J. Ussar, Siegfried Boucher, Jeremie Vernochet, Cecile Mori, Marcelo A. Smyth, Graham Rourk, Michael Cederquist, Carly Rosen, Evan D. Kahn, Barbara B. Kahn, C. Ronald TI Lessons on Conditional Gene Targeting in Mouse Adipose Tissue SO DIABETES LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; HUMAN THP-1 MACROPHAGES; INSULIN-RESISTANCE; BINDING-PROTEIN; CRE RECOMBINASE; IN-VIVO; MEDIATED RECOMBINATION; NERVOUS-SYSTEM; MICE; EXPRESSION AB Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation. To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven. by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter. All three Cre lines demonstrated recombination in the brown and white fat pads. Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat. The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, non-myocyte cells in the skeletal muscle. In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in similar to 2% of spermatozoa. Thus, different "adipocyte-specific" Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology. Diabetes 62:864-874, 2013 C1 [Lee, Kevin Y.; Russell, Steven J.; Ussar, Siegfried; Boucher, Jeremie; Vernochet, Cecile; Mori, Marcelo A.; Smyth, Graham; Rourk, Michael; Cederquist, Carly; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Rosen, Evan D.; Kahn, Barbara B.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu RI Smyth, Gordon/B-5276-2008; OI Smyth, Gordon/0000-0001-9221-2892; Ussar, Siegfried/0000-0001-7575-0920 FU Joslin Training Grant [T32DK-007260]; Human Frontier Sciences Program Long-term Fellowship; National Institutes of Health [DK-60837, -DK 82655]; American Diabetes Association Mentor-Based Award; Mary K. Iacocca Professorship FX This work was supported by a Joslin Training Grant (T32DK-007260) to K.Y.L., a Human Frontier Sciences Program Long-term Fellowship to S.U., and National Institutes of Health Grants DK-60837 and-DK 82655, an American Diabetes Association Mentor-Based Award, and the Mary K. Iacocca Professorship to C.R.K. NR 51 TC 97 Z9 97 U1 1 U2 25 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2013 VL 62 IS 3 BP 864 EP 874 DI 10.2337/db12-1089 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 098NQ UT WOS:000315556400030 PM 23321074 ER PT J AU Zheng, PL Kissler, S AF Zheng, Peilin Kissler, Stephan TI PTPN22 Silencing in the NOD Model Indicates the Type 1 Diabetes-Associated Allele Is Not a Loss-of-Function Variant SO DIABETES LA English DT Article ID REGULATORY T-CELLS; PROTEIN-TYROSINE-PHOSPHATASE; B-LYMPHOCYTES; AUTOIMMUNITY; HOMEOSTASIS; EXPRESSION; HELIOS; LYP AB PTPN22 encodes the lymphoid tyrosine phosphatase (LYP) and is the second strongest non-HLA genetic risk factor for type 1 diabetes. The PTPN22 susceptibility allele generates an LYP variant with an arginine-to-tryptophan substitution at position 620 (R620W) that has been reported by several studies to impart a gain of function. However, a recent report investigating both human cells and a knockin mouse model containing the R620W homolog suggested that this variation causes faster protein degradation. Whether LYP R620W is a gain- or loss-of-function variant, therefore, remains controversial. To address this issue, we generated transgenic NOD mice (nonobese diabetic) in which Ptpn22 can be inducibly silenced by RNA interference. We found that Ptpn22 silencing in the NOD model replicated many of the phenotypes observed in C57BL/6 Ptpn22 knockout mice, including an increase in regulatory T cells. Notably, loss of Ptpn22 led to phenotypic changes in B cells opposite to those reported for the human susceptibility allele. Furthermore, Ptpn22 knockdown did not increase the risk of autoimmune diabetes but, rather, conferred protection from disease. Overall, to our knowledge, this is the first functional study of Ptpn22 within a model of type 1 diabetes, and the data do not support a loss of function for the PTPN22 disease variant. Diabetes 62:896-904, 2013 C1 [Zheng, Peilin; Kissler, Stephan] Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, D-97070 Wurzburg, Germany. [Kissler, Stephan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kissler, S (reprint author), Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, D-97070 Wurzburg, Germany. EM stephan.kissler@joslin.harvard.edu RI Zheng, Peili/B-4360-2015; OI Zheng, Peili/0000-0002-4712-4903; , /0000-0003-3062-7800 FU German Excellence Initiative; Deutsche Forschungsgemeinschaft [FZ82]; Juvenile Diabetes Research Foundation [2-2010-383] FX P.Z. was supported by a grant from the German Excellence Initiative to the Graduate School of Life Sciences of the University of Wurzburg. This work was funded by the Deutsche Forschungsgemeinschaft (FZ82) and by a Career Development Award from the Juvenile Diabetes Research Foundation (2-2010-383) to S.K. The funder played no role in the conduct of the study, collection of data, management of the study, analysis of data, interpretation of data, or preparation of the manuscript. NR 28 TC 25 Z9 25 U1 0 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2013 VL 62 IS 3 BP 896 EP 904 DI 10.2337/db12-0929 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 098NQ UT WOS:000315556400033 PM 23193190 ER PT J AU Ng, MCY Saxena, R Li, J Palmer, ND Dimitrov, L Xu, JZ Rasmussen-Torvik, LJ Zmuda, JM Siscovick, DS Patel, SR Crook, ED Sims, M Chen, YDI Bertoni, AG Li, MY Grant, SFA Dupuis, J Meigs, JB Psaty, BM Pankow, JS Langefeld, CD Freedman, BI Rotter, JI Wilson, JG Bowden, DW AF Ng, Maggie C. Y. Saxena, Richa Li, Jiang Palmer, Nicholette D. Dimitrov, Latchezar Xu, Jianzhao Rasmussen-Torvik, Laura J. Zmuda, Joseph M. Siscovick, David S. Patel, Sanjay R. Crook, Errol D. Sims, Mario Chen, Yii-Der I. Bertoni, Alain G. Li, Mingyao Grant, Struan F. A. Dupuis, Josee Meigs, James B. Psaty, Bruce M. Pankow, James S. Langefeld, Carl D. Freedman, Barry I. Rotter, Jerome I. Wilson, James G. Bowden, Donald W. TI Transferability and Fine Mapping of Type 2 Diabetes Loci in African Americans SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; RISK LOCI; JAPANESE POPULATION; GENETIC-VARIANTS; DISEASES; LINKAGE; METAANALYSIS; REPLICATION; PEDIGREES AB Type 2 diabetes (T2D) disproportionally affects African Americans (AfA) but, to date, genetic variants identified from genome-wide association studies (GWAS) are primarily from European and Asian populations. We examined the single nucleotide polymorphism (SNP) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2,806 T2D case subjects with or without end-stage renal disease and 4,265 control subjects from the Candidate Gene Association Resource Plus Study. Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0.05). The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1.30; P = 6.86 X 10(-8)). Locus-wide analysis demonstrated significant associations (P-emp < 0.05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus. Of these loci, the regional best SNPs were in differential linkage disequilibrium (LD) with the index and adjacent SNPs. Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA. with similar effect sizes. The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations. Diabetes 62:965-976, 2013 C1 [Ng, Maggie C. Y.; Palmer, Nicholette D.; Dimitrov, Latchezar; Bowden, Donald W.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. [Ng, Maggie C. Y.; Li, Jiang; Palmer, Nicholette D.; Xu, Jianzhao; Bowden, Donald W.] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Palmer, Nicholette D.; Bowden, Donald W.] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA. [Rasmussen-Torvik, Laura J.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Patel, Sanjay R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Crook, Errol D.] Univ S Alabama, Coll Med, Ctr Hlth Communities, Mobile, AL USA. [Sims, Mario] Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA. [Chen, Yii-Der I.] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90048 USA. [Chen, Yii-Der I.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Bertoni, Alain G.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Li, Mingyao] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Grant, Struan F. A.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Langefeld, Carl D.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Freedman, Barry I.; Bowden, Donald W.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. RP Ng, MCY (reprint author), Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. EM mng@wakehealth.edu OI Dupuis, Josee/0000-0003-2871-3603; Patel, Sanjay/0000-0002-9142-5172; Pankow, James/0000-0001-7076-483X FU National Institutes of Health (NIH) [HHSC268200782096C]; NIH [K99-DK-081350, R01-DK-066358, R01-DK-053591, R01-11L-56266, R01-DK-070941, HHSN268200625226C]; General Clinical Research Center of the WFSM [M01-RR-07122]; NHLBI; DNA samples through the Massachusetts Institute of Technology-Broad Institute [N01-HC-65226]; NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, BESN268201100010C, HHSN268201100011C, HHSN268201100012C, R01-HL-087641, R01-HL-59367, R01-HL-086694, N02-HL-6-4278]; National Human Genome Research Institute [UOI-HG-004402]; NIH and NIH Roadmap for Medical Research [ULl-RR-025005]; University of Alabama at Birmingham [N01-HC-48047, N01-HC-95095]; University of Minnesota [N01-HC-48048]; Northwestern University [N01-HC-48049]; Kaiser Foundation Research Institute [N01-HC-48050]; Tufts-New England Medical Center [N01-HC-45204]; WFSM [N01-HC-45205]; Harbor-UCLA Research and Education Institute [N01-HC-05187]; University of California Irvine [N01-HC-45134, N01-HC-95100]; CFS is affiliated with Case Western Reserve University [NIH HL-46380, M01-RR-00080]; JHS is affiliated with Jackson State University [N01-HC-95170]; University of Mississippi [N01-HC-95171]; Tougaloo College [N01-HC-95172]; NHLBI in collaboration with MESA investigators; NIMBI [N01-HC-65226]; National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-078616, K24DK-080140]; [N01-HC-95159]; [N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169]; [RR-024156] FX Genotyping services for the WFSM study were provided by the CIDR. CIDR is fully funded through a federal contract from the National Institutes of Health (NIH) to The Johns Hopkins University (Contract HHSC268200782096C). The work at Wake Forest was supported by NIH grants K99-DK-081350 (N.D.P.), R01-DK-066358 (D.W.B.), R01-DK-053591 (D.W.B.), R01-11L-56266 (B.I.F.), and R01-DK-070941 (B.I.F.), and in part by the General Clinical Research Center of the WFSM Grant M01-RR-07122. This work was also supported by the NHLBI. The following five parent studies have contibuted parent study data, ancillary study data, and DNA samples through the Massachusetts Institute of Technology-Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community: ARIC, CARDIA, CFS, JHS, and MESA. ARIC is carried out as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, BESN268201100010C, HHSN268201100011C, and HHSN268201100012C) R01-HL-087641, R01-HL-59367, and R01-HL-086694, National Human Genome Research Institute contract UOI-HG-004402, and NIH contract HHSN268200625226C. Infrastructure was partly supported by Grant ULl-RR-025005, a component of the NIH and NIH Roadmap for Medical Research. CARDIA is affiliated with University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), WFSM (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), and University of California Irvine (N01-HC-45134, N01-HC-95100). CFS is affiliated with Case Western Reserve University (NIH HL-46380 and M01-RR-00080). JHS is affiliated with Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), and Tougaloo College (N01-HC-95172). MESA is conducted and supported by the NHLBI in collaboration with MESA investigators. Support is provided by grants and contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, and RR-024156. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. Funding for CARe genotyping was provided by NIMBI Contract N01-HC-65226. J.B.M. is supported by National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-078616 and K24DK-080140). NR 49 TC 28 Z9 29 U1 1 U2 19 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2013 VL 62 IS 3 BP 965 EP 976 DI 10.2337/db12-0266/-/DC1 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 098NQ UT WOS:000315556400040 PM 23193183 ER PT J AU Brazeau, NF Pinto, EG Harvey, HB Oliveira, GR Pomerantz, BJ Wicky, S Oklu, R AF Brazeau, Nicholas F. Pinto, Erique G. Harvey, Harlan B. Oliveira, George R. Pomerantz, Benjamin J. Wicky, Stephan Oklu, Rahmi TI Critical limb ischemia: an update for interventional radiologists SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Review ID PERIPHERAL ARTERIAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; MAGNETIC-RESONANCE ANGIOGRAPHY; CT ANGIOGRAPHY; OCCLUSIVE DISEASE; BYPASS-SURGERY; ENDOVASCULAR MANAGEMENT; RISK-FACTORS; PREVENT-III AB Critical limb ischemia (CLI) is a growing epidemic with bleak patient outcomes. A variety of treatment modalities have been adopted to address CLI based on comorbidities, life expectancy, and the nature of the arterial disease. With advances in technology and treatment strategies, the clinical outcomes of CLI patients have significantly improved over recent years. However, despite progress, patency rates of both surgical and endovascular interventions, limb-salvage and amputation rates are still dismal. We review the epidemiology, treatment strategies, imaging modalities, and the microcirculation aspect of CLI. C1 [Brazeau, Nicholas F.; Harvey, Harlan B.; Oliveira, George R.; Wicky, Stephan; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc Imaging & Intervent, Boston, MA 02115 USA. [Pinto, Erique G.] Hosp Prof Doutor Fernando Fonseca, Dept Imaging, Amadora, Portugal. [Pomerantz, Benjamin J.] Kalispell Reg Med Ctr, Dept Radiol, Kalispell, MT USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc Imaging & Intervent, Boston, MA 02115 USA. EM rahmioklu@gmail.com NR 60 TC 1 Z9 2 U1 0 U2 7 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD MAR-APR PY 2013 VL 19 IS 2 BP 173 EP 180 DI 10.4261/1305-3825.DIR.5955-12.1 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 101CO UT WOS:000315753000015 PM 23233402 ER PT J AU Yoon, WJ Daglilar, ES Pitman, MB Brugge, WR AF Yoon, W. J. Daglilar, E. S. Pitman, M. B. Brugge, W. R. TI Cystic pancreatic neuroendocrine tumors: endoscopic ultrasound and fine-needle aspiration characteristics SO ENDOSCOPY LA English DT Article ID FLUID CARCINOEMBRYONIC ANTIGEN; ENDOCRINE NEOPLASMS; PREOPERATIVE DIAGNOSIS; FEATURES; EUS AB Background and study aims: Limited data are available on the endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) characteristics of cystic pancreatic neuroendocrine tumors (CPanNets). The aims of this study were to describe the EUS and FNA characteristics of pathologically confirmed CPanNets and to compare these characteristics with mucinous cysts from matched patients. Patients and methods: From an EUS-FNA database (between 1999 and 2011), 19 patients with a pathologically confirmed CPanNet were identified. Patient characteristics, cyst fluid carcinoembryonic antigen (CEA) levels, pathology, and EUS findings were analyzed. For comparison, age- and sex-matched patients with mucinous cysts were randomly chosen from the same database. Results: Of the 19 patients, two had multiple endocrine neoplasia type 1 and two had metastases. The median diameter of the lesions was 24 mm. EUS revealed unilocular lesions in 7 patients, thinly septated lesions with thin walls in 1, and mixed solid-cystic lesions in 11. EUS-FNA cytology confirmed neoplasm in 12 of the 19 patients (63.2%). The median cyst fluid CEA level (n=15) was 1.1 ng/mL (range 0.3-500 ng/mL). Compared with matched patients with mucinous cysts, the median cyst fluid CEA was lower (1.1 ng/mL vs. 400 ng/mL), thick walls were more common (66.7% vs. 13.3%), and diagnostic cytology was more likely (73.3% vs. 20.0%). Conclusions: Analysis of EUS and FNA results showed that the cyst fluid from CPanNets had a lower CEA concentration, a higher frequency of thick walls on EUS, and higher diagnostic cytology compared with mucinous cysts. These findings may aid in the diagnosis of CPanNets. C1 [Yoon, W. J.; Daglilar, E. S.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Pitman, M. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brugge, W. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM wbrugge@partners.org FU 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) [8UL1TR000170-05]; Harvard University FX This work was conducted with support from 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 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 27 TC 14 Z9 14 U1 0 U2 5 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD MAR PY 2013 VL 45 IS 3 BP 189 EP 194 DI 10.1055/s-0032-1325990 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 098RI UT WOS:000315566000006 PM 23296363 ER PT J AU Beardsley, RM Suhler, EB Rosenbaum, JT Lin, P AF Beardsley, Robert M. Suhler, Eric B. Rosenbaum, James T. Lin, Phoebe TI Pharmacotherapy of scleritis: current paradigms and future directions SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE alkylating agent; antimetabolite; biologic response modifier; noninfectious; scleritis; therapy ID JUVENILE IDIOPATHIC ARTHRITIS; INFLAMMATORY EYE DISEASE; NONNECROTIZING ANTERIOR SCLERITIS; SYSTEMIC AUTOIMMUNE-DISEASE; PRIMARY SJOGRENS-SYNDROME; TERM-FOLLOW-UP; RHEUMATOID-ARTHRITIS; WEGENERS-GRANULOMATOSIS; BEHCETS-DISEASE; LONG-TERM AB Introduction: Scleritis is an inflammatory condition affecting the eye wall that may be associated with a number of systemic inflammatory diseases. Because scleritis can be refractory to standard treatment, knowledge of the body of available and emerging therapies is paramount and is reviewed here. Areas covered: This review focuses on both traditional and emerging therapies for noninfectious scleritis. The authors cover the mechanisms of action and potential adverse effects of each of the treatment modalities. In addition, a summary of the significant MEDLINE indexed literature under the subject heading 'scleritis', 'treatment', 'immunomodulator' will be provided on each therapy, including commentary on appropriate use and relative contra-indications. Novel treatments and potential drug candidates that are currently being evaluated in clinical trials with therapeutic potential will also be reviewed. Expert opinion: While oral nonsteroidal anti-inflammatory drugs and oral corticosteroids are widely used, effective, first-line agents for inflammatory scleritis, refractory cases require antimetabolites, T-cell inhibitors, or biologic response modifiers. In particular, there is emerging evidence for the use of targeted biologic response modifiers, and potentially, for local drug delivery. C1 [Beardsley, Robert M.; Suhler, Eric B.; Rosenbaum, James T.; Lin, Phoebe] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Rosenbaum, James T.] Devers Eye Inst, Portland, OR USA. RP Lin, P (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM linp@ohsu.edu FU Department of Veterans Affairs; RPB (research to prevent blindness); Aquinox; Mitotech; [IK08EY022948-01] FX P Lin has received IK08EY022948-01 grant support. Eric B Suhler runs clinical trials for BMS, Genentech, Eyegate, Novartis and Abbott. He is supported by the Department of Veterans Affairs and by an RPB (research to prevent blindness) grant. James T Rosenbaum runs clinical trials for BMS, Eyegate, Genentech, Novartis and Abbott. He also consults for Teva, Regeneron, Santen, Allergan, Novartis, UCB, Amgen, Elan. He also has research grants from Aquinox and Mitotech. NR 141 TC 8 Z9 8 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD MAR PY 2013 VL 14 IS 4 BP 411 EP 424 DI 10.1517/14656566.2013.772982 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 096OT UT WOS:000315414800005 PM 23425055 ER PT J AU Kohan, R Carabelos, MN Xin, WN Sims, K Guelbert, N Cismondi, IA Pons, P Alonso, GI Troncoso, M Witting, S Pearce, DA de Kremer, RD Oller-Ramirez, AM de Halac, IN AF Kohan, Romina Noelia Carabelos, Maria Xin, Winnie Sims, Katherine Guelbert, Norberto Adriana Cismondi, Ines Pons, Patricia Irene Alonso, Graciela Troncoso, Monica Witting, Scarlet Pearce, David A. Dodelson de Kremer, Raquel Maria Oller-Ramirez, Ana Noher de Halac, Ines TI Neuronal ceroid lipofuscinosis type CLN2: A new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America SO GENE LA English DT Article DE Neuronal ceroid lipofuscinoses; Tripeptidyl-peptidase 1; TPP1/CLN2 gene; Phenotype; South American population; Mutational spectrum ID PROGRESSIVE MYOCLONIC EPILEPSY; TRIPEPTIDYL-PEPTIDASE-I; CATHEPSIN-D DEFICIENCY; CHANNEL-RELATED GENE; TRANSMEMBRANE PROTEIN; BATTEN-DISEASE; ANTISENSE OLIGONUCLEOTIDES; CELLULAR PATHOLOGY; MUTANT MICE; MUTATIONS AB Tripeptidyl-peptidase 1 (TPP1) null or residual activity occurs in neuronal ceroid lipofuscinosis (NCL) with underlying TPP1/CLN2 mutations. A survey of 25 South American CLN2 affected individuals enabled the differentiation of two phenotypes: classical late-infantile and variant juvenile, each in approximately 50% of patients, with residual TPP1 activity occurring in approximately 32%. Each individual was assigned to one of three subgroups: (I) n = 11, null TPP1 activity in leukocytes; (II) n = 8, residual TPP1 activity of 0.60-15.85 nmol/h/mg (nr 110-476); (III) n = 6, activity not measured in leukocytes. Curvilinear bodies (0) appeared in almost all studied CLN2 subjects; the only exceptions occurred in cases of subgroup II: two individuals had combined CBs/fingerprints (FPs), and one case had pure FPs. There were 15 mutations (4 first published in this paper, 3 previously observed in South America by our group, and 8 previously observed by others). In subgroup I, mutations were either missense or nonsense; in subgroups II and III, mutations prevailed at the non-conserved intronic site, c.887 - 10A>G (intron 7), and to a lesser extent at c.89 + 5G>C (intron 2), in heterozygous combinations. Grouping phenotypically and genetically known individuals on the basis of TPP1 activity supported the concept that residual enzyme activity underlies a protracted disease course. The prevalence of intronic mutations at non-conserved sites in subgroup II individuals indicates that some alternative splicing might allow some residual TPP1 activity. (c) 2013 Elsevier B.V. All rights reserved. C1 [Kohan, Romina; Noelia Carabelos, Maria; Guelbert, Norberto; Adriana Cismondi, Ines; Irene Alonso, Graciela; Dodelson de Kremer, Raquel; Maria Oller-Ramirez, Ana; Noher de Halac, Ines] Univ Nacl Cordoba, Fac Ciencias Med, Catedra Clin Pediat, Ctr Estudio Metabolopatias Congenitas CEMECO, RA-5014 Cordoba, Argentina. [Kohan, Romina; Adriana Cismondi, Ines] Univ Nacl Cordoba, Fac Odontol, RA-5000 Cordoba, Argentina. [Kohan, Romina] Univ Nacl Cordoba, Secretaria Ciencia & Tecnol SECyT, RA-5000 Cordoba, Argentina. [Xin, Winnie; Sims, Katherine] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA. [Pons, Patricia] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Microscopia Elect, RA-5000 Cordoba, Argentina. [Troncoso, Monica; Witting, Scarlet] Hosp Clin San Borja Arriaran, Serv Neuropsiquiatria Infantil, Santiago, Chile. [Pearce, David A.] Sanford Res USD, Sanford Childrens Hlth Res Ctr, Sioux Falls, SD USA. [Noher de Halac, Ines] Consejo Nacl Invest Cient & Tecn CONICET, Buenos Aires, DF, Argentina. RP de Halac, IN (reprint author), Univ Nacl Cordoba, Fac Ciencias Med, CEMECO, Ferroviarios 1250, RA-5014 Cordoba, Argentina. EM nclcemeco@nclcemeco.com.ar FU Argentinean National Research Council (CONICET-RA); Secretary of Science and Technology of the National University Cordoba (SECyT-UNC); Batten Disease Support and Research Association (BDSRA-US); NIH-Fogarty [R21TW00843301-US]; von Humboldt Foundation FX We are especially grateful to the NCL families of South America. We also acknowledge the personnel of the Center for the Study of Inborn Errors of Metabolism (CEMECO) at the Children's Hospital, Cordoba, Argentina; Hugo Arroyo, Liliana Czornij, Soledad Monges, and Mariana Loos from the Hospital Garrahan, Buenos Aires, Argentina; Alejandra Barile and Adriana Becerra from the Children's Hospital, Cordoba, Argentina; Ana Lia Taratuto, Mercedes Villanueva, and Santiago Vazquez from the Foundation for Neurological Disease Control for Children (FLENI), Buenos Aires, Argentina; and all of the pediatricians, ophthalmologists, radiologists, physiotherapists, and other professionals that care for the patients and their families. We also thank the laboratory personnel in the Neurogenetics DNA Diagnostic Laboratory, Massachusetts General Hospital, Boston; Michael Fietz and Viv Muller from Women's and Children's Hospital, Adelaide, Australia; Hans H. Goebel, Alfried Kohlschutter, Zoltan Luckacs, and Robert Steinfeld from Mainz and Hamburg Universities, Germany; and Sara E. Mole from the MRC Laboratory for Molecular Cell Biology, University College London, UK We thank the organizations that provided grant support to the investigation during the last 5 years: Argentinean National Research Council (CONICET-RA); Secretary of Science and Technology of the National University Cordoba (SECyT-UNC); Batten Disease Support and Research Association (BDSRA-US), especially its former executive director, Mr. Lance Johnston; NIH-Fogarty R21TW00843301-US; and the von Humboldt Foundation, which provided grant support for INH's travels to Germany. NR 70 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR PY 2013 VL 516 IS 1 BP 114 EP 121 DI 10.1016/j.gene.2012.12.058 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 095XE UT WOS:000315367500016 PM 23266810 ER PT J AU Koika, V Varnavas, P Valavani, H Sidis, Y Plummer, L Dwyer, A Quinton, R Kanaka-Gantenbein, C Pitteloud, N Sertedaki, A Dacou-Voutetakis, C Georgopoulos, NA AF Koika, Vasiliki Varnavas, Petros Valavani, Helen Sidis, Yisrael Plummer, Lacey Dwyer, Andrew Quinton, Richard Kanaka-Gantenbein, Christine Pitteloud, Nelly Sertedaki, Amalia Dacou-Voutetakis, Catherine Georgopoulos, Neoklis A. TI Comparative functional analysis of two fibroblast growth factor receptor 1 (FGFR1) mutations affecting the same residue (R254W and R254Q) in isolated hypogonadotropic hypogonadism (IHH) SO GENE LA English DT Article DE Kallmann syndrome; Anosmia; IHH; KS; GnRH deficiency ID KALLMANN-SYNDROME; HORMONE DEFICIENCY; STRUCTURAL BASIS; GENETICS; DIMERIZATION; ACTIVATION; ANOSMIA AB FGFR1 mutations have been identified in both Kallmann syndrome and normosmic HH (nIHH). To date, few mutations in the FGFR1 gene have been structurally or functionally characterized in vitro to identify molecular mechanisms that contribute to the disease pathogenesis. We attempted to define the in vitro functionality of two FGFR1 mutants (R254W and R254Q), resulting from two different amino add substitutions of the same residue, and to correlate the in vitro findings to the patient phenotypes. Two unrelated GnRH deficient probands were found to harbor mutations in FGFR1 (R254W and R254Q). Mutant signaling activity and expression levels were evaluated in vitro and compared to a wild type (WT) receptor. Signaling activity was determined by a FGF2/FGFR1 dependent transcription reporter assay. Receptor total expression levels were assessed by Western blot and cell surface expression was measured by a radiolabeled antibody binding assay. The R254W maximal receptor signaling capacity was reduced by 45% (p<0.01) while R254Q activity was not different from WT. However, both mutants displayed diminished total protein expression levels (40 and 30% reduction relative to WT, respectively), while protein maturation was unaffected. Accordingly, cell surface expression levels of the mutant receptors were also significantly reduced (35% p<0.01 and 15% p<0.05, respectively). The p.R254W and p.R254Q are both loss-of-function mutations as demonstrated by their reduced overall and cell surface expression levels suggesting a deleterious effect on receptor folding and stability. It appears that a tryptophan substitution at R254 is more disruptive to receptor structure than the more conserved glutamine substitution. No clear correlation between the severity of in vitro loss-of-function and phenotypic presentation could be assigned. (C) 2012 Elsevier B.V. All rights reserved. C1 [Koika, Vasiliki; Varnavas, Petros; Georgopoulos, Neoklis A.] Univ Patras, Sch Med, Div Reprod Endocrinol, Dept Obstet & Gynecol, Patras 26500, Greece. [Valavani, Helen; Kanaka-Gantenbein, Christine; Sertedaki, Amalia; Dacou-Voutetakis, Catherine] Univ Athens, Sch Med, Dept Pediat 1, Div Endocrinol Diabet & Metab, GR-11527 Athens, Greece. [Sidis, Yisrael; Dwyer, Andrew; Pitteloud, Nelly] Univ Lausanne, Dept Physiol, Sch Biol & Med, Lausanne, Switzerland. [Sidis, Yisrael; Dwyer, Andrew; Pitteloud, Nelly] Serv Endocrinol, Lausanne, Switzerland. [Plummer, Lacey] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Quinton, Richard] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Koika, V (reprint author), Univ Patras, Univ Hosp, Div Reprod Endocrinol, Dept Obstet & Gynecol,Med Sch, Patras 26500, Greece. EM vkoika@upatras.gr RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; NR 25 TC 7 Z9 7 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR PY 2013 VL 516 IS 1 BP 146 EP 151 DI 10.1016/j.gene.2012.12.041 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 095XE UT WOS:000315367500022 PM 23276709 ER PT J AU Jakobiec, FA Yoon, MK AF Jakobiec, Frederick A. Yoon, Michael K. TI Histopathologic proof for the origin of ectopic cilia of the eyelid skin SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE Cilia; Ectopic eyelashes; Distichiasis; Eyelids ID EYELASHES AB The origin of congenitally displaced cilia of the eyelid margin remains a controversial subject. Case report with literature review. The clinical, surgical, and histopathologic findings of the current and published cases were used to determine the location of the generative hair bulbs of ectopic cilia. A 36 year-old man underwent complete excision of a congenital papule containing approximately 25 cilia located in the left lateral upper eyelid. These cilia were separated by 3 mm superior from the normal cilia where there was a miniscule gap. The hair bulbs were located in dense fibrous tissue at the level of the lower dermis but above the orbicularis striated muscle, which during surgery was not defective or colobomatous. This case supplies additional evidence that ectopic eyelid cilia arise in the eyelid skin and not as has been postulated within metaplastic Meibomian glands of the tarsus. C1 [Jakobiec, Frederick A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Yoon, Michael K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St 3rd Floor, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 20 TC 2 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD MAR PY 2013 VL 251 IS 3 BP 985 EP 988 DI 10.1007/s00417-012-2224-0 PG 4 WC Ophthalmology SC Ophthalmology GA 096PY UT WOS:000315418000047 PM 23263620 ER PT J AU Jakobiec, FA Callahan, AB Zakka, FR AF Jakobiec, Frederick A. Callahan, Alison B. Zakka, Fouad R. TI Intraocular PAS-positive macrophages simulating Whipple's disease SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID OCULAR INVOLVEMENT; ENDOPHTHALMITIS; BACILLUS; LIGHT C1 [Jakobiec, Frederick A.; Callahan, Alison B.; Zakka, Fouad R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol,Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD MAR PY 2013 VL 251 IS 3 BP 1033 EP 1036 DI 10.1007/s00417-012-2070-0 PG 4 WC Ophthalmology SC Ophthalmology GA 096PY UT WOS:000315418000068 PM 22669409 ER PT J AU May, T Shoni, M Crum, CP Xian, W Vathipadiekal, V Birrer, M Rosen, B Tone, A Murphy, KJ AF May, Taymaa Shoni, Melina Crum, Christopher P. Xian, Wa Vathipadiekal, Vinod Birrer, Michael Rosen, Barry Tone, Alicia Murphy, K. Joan TI Low-grade and high-grade serous Mullerian carcinoma: Review and analysis of publicly available gene expression profiles SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian carcinoma; Fallopian tube carcinoma; Low-grade serous carcinoma; High-grade serous carcinoma; Gene expression analysis; Taxane resistance ID EPITHELIAL OVARIAN-CANCER; MALIGNANT POTENTIAL TUMORS; FALLOPIAN-TUBE EPITHELIUM; IMATINIB MESYLATE; MUTATIONAL ANALYSIS; CLINICAL-TRIALS; 2-TIER SYSTEM; CELL-LINES; STAGE-III; NEW-MODEL AB Objective. Mullerian low grade serous carcinoma (LGSC) and high grade serous carcinoma (HGSC) have distinct molecular profiles, clinical behavior and treatment response. Our objective was to study the biological profiles of these carcinomas. Methods. This study examines publicly available gene expression profiles. of LGSC and HGSC to identify differentially expressed genes and key pathways involved in carcinogenesis and chemotherapy response. Results. Our analysis supports the hypothesis that serous mullerian carcinoma develop through two different pathways yielding two distinct malignancies, namely LGSC and HGSC. Furthermore, genes potentially involved in chemotherapeutic resistance of LGSC were identified. Suppressing the levels of these genes/proteins may increase clinical response to standard chemotherapy in patients with LGSC. Conclusion. In summary, this review shows the molecular profile of LGSC and HGSC through multi-center analysis of gene expression profiles of these tumors. The gene signatures of these neoplasms may potentially be used to develop disease-specific, targeted therapy for LGSC and HGSC. (C) 2012 Elsevier Inc. All rights reserved. C1 [May, Taymaa; Shoni, Melina] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02115 USA. [Crum, Christopher P.; Xian, Wa] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Pathol,Div Gynecol Oncol, Boston, MA 02115 USA. [Vathipadiekal, Vinod; Birrer, Michael] Harvard Univ, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Rosen, Barry; Murphy, K. Joan] Princess Margaret Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Toronto, ON M4X 1K9, Canada. [Tone, Alicia] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. RP May, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM tmay1@partners.org OI Vathipadiekal, Vinod/0000-0002-8181-6890 NR 60 TC 7 Z9 7 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2013 VL 128 IS 3 BP 488 EP 492 DI 10.1016/j.ygyno.2012.12.009 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 095FU UT WOS:000315320900014 PM 23253401 ER PT J AU Kagee, A Tsai, AC Lund, C Tomlinson, M AF Kagee, Ashraf Tsai, Alexander C. Lund, Crick Tomlinson, Mark TI Screening for common mental disorders in low resource settings: reasons for caution and a way forward SO INTERNATIONAL HEALTH LA English DT Article DE Screening; Common mental disorders; Low and middle income countries ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; HEALTH-WORKERS; DEPRESSION; INTERVENTION; METAANALYSIS; INSTRUMENTS; MEDICATION; THERAPY AB Recognition of high rates of common mental disorders in many resource-constrained contexts has indicated the need for routine screening of patients attending public health facilities. Screening may facilitate entry into community level psychiatric services for those identified as disordered. Yet, screening instruments will need to ensure high specificity so as to minimise expenditures on treating false positives. Task shifting of screening activities to primary health care staff and lay workers in low income settings may hold some population-level advantages, including greater population coverage, more efficient deployment of health care staff, and the reduction of stigma if specific conditions are met. C1 [Kagee, Ashraf; Tomlinson, Mark] Univ Stellenbosch, Dept Psychol, ZA-7602 Matieland, South Africa. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Lund, Crick; Tomlinson, Mark] Univ Cape Town, Dept Psychiat & Mental Hlth, Alan J Flisher Ctr Publ Mental Hlth, ZA-7700 Cape Town, South Africa. RP Kagee, A (reprint author), Univ Stellenbosch, Dept Psychol, Private Bag X1, ZA-7602 Matieland, South Africa. EM skagee@sun.ac.za OI Tsai, Alexander/0000-0001-6397-7917 FU Medical Research Council (South Africa); U.S. National Institutes of Health [K23 MH-096620]; National Research Foundation (South Africa); Department for International Development (DfID-UK); U.S National Institute of Mental Health [U19MH095699-02] FX AK acknowledges support from the Medical Research Council (South Africa). ACT acknowledges salary support from the U.S. National Institutes of Health K23 MH-096620. MT acknowledges support from National Research Foundation (South Africa). MT and CL acknowledge support from the Department for International Development (DfID-UK). CL acknowledges support from the U.S National Institute of Mental Health U19MH095699-02. The opinions expressed in this article do not necessarily reflect those of the funders. NR 19 TC 32 Z9 34 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1876-3413 J9 INT HEALTH JI Int. Health PD MAR PY 2013 VL 5 IS 1 BP 11 EP 14 DI 10.1093/inthealth/ihs004 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 099UI UT WOS:000315647500005 PM 23580905 ER PT J AU Huang, SS Han, DY Wang, GJ Yuan, YY Song, YS Han, MY Chen, ZY Dai, P AF Huang, Shasha Han, Dongyi Wang, Guojian Yuan, Yongyi Song, Yueshuai Han, Mingyu Chen, Zhengyi Dai, Pu TI Sensorineural hearing loss caused by mutations in two alleles of both GJB2 and SLC26A4 genes SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Sensorineural hearing loss; Autosomal recessive; Double-allele mutations; Different genes ID ENLARGED VESTIBULAR AQUEDUCT; MOLECULAR ETIOLOGY; PENDRED-SYNDROME; DEAFNESS; IMPAIRMENT; SPECTRUM; POPULATION; PREVALENCE; CHINA AB Background: Most studies of the molecular etiology of sensorineural hearing loss have described deafness as a monogenic disease encompassing double-allele mutations for patients with autosomal recessive deafness. Here, we report the first case of autosomal recessive genetic deafness in an enlarged vestibular aqueduct syndrome (EVAS) patient With biallelic mutations in two deafness genes. Methods: Temporal computed tomography (CT), complete physical and otoscopic examinations, and an audiological study, including tympanometry, pure-tone audiometry or auditory steady-state response (ASSR), were carried out. Exon 2 of GJB2 and the coding exons of SLC26A4 were sequenced. Results: A patient with an enlarged vestibular aqueduct was found to carry c.1229C>T/c.1079C>T compound heterozygous mutations in SLC26A4. This individual also carried c.257C>G/c.299-300delAT compound heterozygous mutations in GJB2. As a result, the recurrent risk of the patient's siblings increased significantly from 25% for typical autosomal recessive deafness to 43.75%. Conclusions: The findings of the present study challenge the traditional diagnostic strategy in which testing is generally considered complete upon identification of a double-allele mutation within one gene, with significant implications for genetic counseling and risk prediction. Our results suggest that, with advances in sequencing technology, it will be possible and necessary to test all known deafness genes in the near future, as this will likely allow more accurate genetic counseling of patients. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Huang, Shasha; Han, Dongyi; Wang, Guojian; Yuan, Yongyi; Song, Yueshuai; Han, Mingyu; Dai, Pu] Peoples Liberat Army Gen Hosp, Dept Otolaryngol, Beijing, Peoples R China. [Huang, Shasha; Wang, Guojian; Yuan, Yongyi; Song, Yueshuai; Han, Mingyu; Dai, Pu] PIA Gen Hosp, Hainan Branch, Dept Otolaryngol, Sanya, Peoples R China. [Chen, Zhengyi] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dai, P (reprint author), Peoples Liberat Army Gen Hosp, Dept Otolaryngol, Beijing, Peoples R China. EM Zheng-Yi_Chen@meeil.harvard.edu; daipu301@vip.sina.com FU Project of the National Natural Science Foundation of China [30801285, 31071099, 81000415]; State 863 High Technology R&D Key Project of China [2011AA02A112]; Ministery of Science and Technology of China [2012BAI09B02]; Ministery of Health of China [201202005]; New Star Program of Beijing Science and Technology [2009 B 34, 2010B081] FX This work was supported by grants from the Project of the National Natural Science Foundation of China (Grant No.30801285, 31071099, 81000415), grant from State 863 High Technology R&D Key Project of China (2011AA02A112), grant from Ministery of Science and Technology of China (2012BAI09B02), grant from Ministery of Health of China (201202005) and the New Star Program of Beijing Science and Technology (Grant No. 2009 B 34, 2010B081). We thank the patients and families for their participation in this study. NR 26 TC 5 Z9 7 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD MAR PY 2013 VL 77 IS 3 BP 379 EP 383 DI 10.1016/j.ijporl.2012.11.031 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 095XF UT WOS:000315367600015 PM 23266159 ER PT J AU Kuusikko-Gauffin, S Pollock-Wurman, R Mattila, ML Jussila, K Ebeling, H Pauls, D Moilanen, I AF Kuusikko-Gauffin, Sanna Pollock-Wurman, Rachel Mattila, Marja-Leena Jussila, Katja Ebeling, Hanna Pauls, David Moilanen, Irma TI Social Anxiety in Parents of High-Functioning Children with Autism and Asperger Syndrome SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Adult; Age; Autism spectrum disorders; Gender; Social anxiety; SPAI ID SPECTRUM DISORDERS; PHOBIA; INVENTORY; VALIDITY; ADOLESCENTS; COMORBIDITY; FAMILIES; SAMPLE; DISCRIMINANT; ALEXITHYMIA AB We evaluated social anxiety (SA) symptoms in parents of children with autism spectrum disorders (ASDs; N = 131) and community parents (N = 597) using the Social Phobia and Anxiety Inventory (SPAI). SA was significantly more common in ASD than control mothers (15.6 vs. 6.7 %) and more equal between the ASD and control fathers (3.3 vs. 4.8 %). The ASD mothers scored significantly higher than control mothers on all SPAI scales. ASD fathers scored significantly higher than control fathers on the somatic, cognitive, avoidance and agoraphobic symptoms of SA. It is of clinical import to support ASD parents' well-being as their psychiatric features may contribute greatly to their children's emotional development and the well-being of the whole family. C1 [Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jussila, Katja; Ebeling, Hanna; Moilanen, Irma] Univ & Univ Hosp Oulu, Fac Med, Inst Clin Med, Dept Child Psychiat, Oulu 90029, Finland. [Pollock-Wurman, Rachel; Pauls, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kuusikko-Gauffin, S (reprint author), Univ & Univ Hosp Oulu, Fac Med, Inst Clin Med, Dept Child Psychiat, POB 26, Oulu 90029, Finland. EM Sanna.kuusikko-gauffin@oulu.fi NR 51 TC 12 Z9 12 U1 4 U2 46 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAR PY 2013 VL 43 IS 3 BP 521 EP 529 DI 10.1007/s10803-012-1581-1 PG 9 WC Psychology, Developmental SC Psychology GA 095LU UT WOS:000315336800002 PM 22733299 ER PT J AU Scahill, L Hallett, V Aman, MG McDougle, CJ Arnold, LE McCracken, JT Tierney, E Deng, YH Dziura, J Vitiello, B AF Scahill, Lawrence Hallett, Victoria Aman, Michael G. McDougle, Christopher J. Arnold, L. Eugene McCracken, James T. Tierney, Elaine Deng, Yanhong Dziura, James Vitiello, Benedetto CA Res Units Pediatric TI Brief Report: Social Disability in Autism Spectrum Disorder: Results from Research Units on Pediatric Psychopharmacology (RUPP) Autism Network Trials SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Social disability; Autism; Research Units on Pediatric Psychopharmacology (RUPP) Autism Network; Social withdrawal; Risperidone; Aberrant Behavior Checklist ID PERVASIVE DEVELOPMENTAL DISORDERS; ABERRANT BEHAVIOR CHECKLIST; YOUNG-PEOPLE; CHILDREN; RISPERIDONE; SYMPTOMS; IRRITABILITY; ARIPIPRAZOLE; INDIVIDUALS; ADOLESCENTS AB There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials. We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded, multi-site, randomized trials with risperidone. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. Study 2 included 49 subjects assigned to risperidone only and 75 subjects assigned to risperidone plus parent training. After 8 weeks of treatment, all active treatments were superior to placebo (effect sizes ranging from 0.42 to 0.65). The findings suggest that the Social Withdrawal subscale may be a useful measure of social disability in acute treatment trials. C1 [Scahill, Lawrence; Hallett, Victoria] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Scahill, Lawrence; Hallett, Victoria] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Aman, Michael G.; Arnold, L. Eugene] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [McDougle, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lurie Ctr Autism, Boston, MA USA. [McDougle, Christopher J.] Indiana Univ, Indinapolis, IN USA. [McCracken, James T.] Univ Calif Los Angeles, Div Child Psychiat, Los Angeles, CA USA. [Tierney, Elaine] Johns Hopkins Univ, Baltimore, MD USA. [Tierney, Elaine] Kennedy Krieger Inst, Baltimore, MD USA. [Deng, Yanhong] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Dziura, James] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. RP Scahill, L (reprint author), Emory Univ, Dept Pediat, 1920 Briarcliff Rd, Atlanta, GA 30329 USA. EM lawrence.scahill@emory.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU NCATS NIH HHS [UL1 TR001108]; NCRR NIH HHS [UL1 RR025761, UL1 RR024139, UL1 RR025755]; NIDA NIH HHS [N01MH80011]; NIMH NIH HHS [U10 MH066768, U10MH66766, N01MH70009, K24 MH001805, U10 MH066764, U01 MH070009, U10MH66768, N01MH80011, N01MH70010, U10 MH066766, U01 MH070010, U10MH66764, N01MH70001] NR 28 TC 13 Z9 13 U1 1 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAR PY 2013 VL 43 IS 3 BP 739 EP 746 DI 10.1007/s10803-012-1689-3 PG 8 WC Psychology, Developmental SC Psychology GA 095LU UT WOS:000315336800020 PM 23104617 ER PT J AU Balkaya, M Krober, JM Rex, A Endres, M AF Balkaya, Mustafa Kroeber, Jan M. Rex, Andre Endres, Matthias TI Assessing post-stroke behavior in mouse models of focal ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE behavior; focal ischemia; functional outcome; sensory-motor tests; stroke ID MIDDLE CEREBRAL-ARTERY; SPINAL-CORD-INJURY; FUNCTIONAL RECOVERY; EXPERIMENTAL STROKE; COGNITIVE DEFICITS; BRAIN ISCHEMIA; STAIRCASE TEST; GAIT ANALYSIS; MICE; SENSORIMOTOR AB Experimental treatment strategies and neuroprotective drugs that showed therapeutic promise in animal models of stroke have failed to produce beneficial effects in human stroke patients. The difficulty in translating preclinical findings to humans represents a major challenge in cerebrovascular research. The reasons behind this translational road block might be explained by a number of factors, including poor quality control in various stages of the research process, the validity of experimental stroke models, and differences in drug administration and pharmacokinetics. Another major difference between animal studies and clinical trials is the choice of end point or outcome measures. Here, we discuss the necessity of poststroke behavioral testing to bridge the gap between clinical and experimental end points. We review established sensory-motor tests for outcome determination after focal ischemia based on the published literature as well as our own personal experience. Selected tests are described in more detail and good laboratory practice standards for behavioral testing are discussed. This review is intended for stroke researchers planning to use behavioral testing in mice. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 330-338; doi:10.1038/jcbfm.2012.185; published online 12 December 2012 C1 [Balkaya, Mustafa; Kroeber, Jan M.; Rex, Andre; Endres, Matthias] Charite, Neurol Klin & Poliklin, D-13353 Berlin, Germany. [Balkaya, Mustafa; Kroeber, Jan M.; Rex, Andre; Endres, Matthias] Charite, Ctr Stroke Res Berlin, D-13353 Berlin, Germany. [Balkaya, Mustafa] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Charlestown, MA 02129 USA. [Balkaya, Mustafa] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Balkaya, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, 149 13th St, Charlestown, MA 02129 USA. EM mgokalpbalkaya@partners.org NR 75 TC 31 Z9 31 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2013 VL 33 IS 3 BP 330 EP 338 DI 10.1038/jcbfm.2012.185 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 099AG UT WOS:000315590200003 PM 23232947 ER PT J AU Kassam, A Skiadaresis, J Habib, S Alexander, S Wolfe, J AF Kassam, Alisha Skiadaresis, Julia Habib, Sharifa Alexander, Sarah Wolfe, Joanne TI Moving Toward Quality Palliative Cancer Care: Parent and Clinician Perspectives on Gaps Between What Matters and What Is Accessible SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHILDREN; LIFE; END; PROGNOSIS; SYMPTOMS; THERAPY; GOALS AB Purpose The National Consensus Project (NCP) published a set of standards for quality palliative care delivery. A key step before applying these guidelines to pediatric oncology is to evaluate how much families and clinicians value these standards. We aimed to determine which elements of palliative care are considered important according to bereaved parents and pediatric oncology clinicians and to determine accessibility of these elements. Methods We administered questionnaires to 75 bereaved parents (response rate, 54%) and 48 pediatric oncology clinicians (response rate, 91%) at a large teaching hospital. Outcome measures included importance ratings and accessibility of core elements of palliative care delivery. Results Fifteen of 20 core elements were highly valued by both parents and clinicians (defined as > 60% of parents and clinicians reporting the item as important). Compared with clinicians, parents gave higher ratings to receiving cancer-directed therapy during the last month of life (P < .01) and involvement of a spiritual mentor (P = .03). Of the valued elements, only three were accessible more than 60% of the time according to clinicians and parents. Valued elements least likely to be accessible included a direct admission policy to hospital, sibling support, and parent preparation for medical aspects surrounding death. Conclusion Parents and clinicians highly value a majority of palliative care elements described in the NCP framework. Children with advanced cancer may not be receiving key elements of palliative care despite parents and clinicians recognizing them as important. Evaluation of barriers to provision of quality palliative care and strategies for overcoming them are critical. J Clin Oncol 31: 910-915. (C) 2012 by American Society of Clinical Oncology C1 [Kassam, Alisha; Skiadaresis, Julia; Habib, Sharifa; Alexander, Sarah] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Kassam, Alisha; Skiadaresis, Julia; Habib, Sharifa; Alexander, Sarah] Univ Toronto, Toronto, ON, Canada. [Wolfe, Joanne] Harvard Univ, Childrens Hosp, Dana Farber Canc Insitute, Sch Med, Boston, MA 02115 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Dana 1103,450 Brookline Ave, Boston, MA 02215 USA. EM joanne_wolfe@dfci.harvard.edu FU Pediatric Oncology Group of Ontario FX Supported by the Pediatric Oncology Group of Ontario. NR 21 TC 17 Z9 17 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2013 VL 31 IS 7 BP 910 EP 915 DI 10.1200/JCO.2012.44.8936 PG 6 WC Oncology SC Oncology GA 097AU UT WOS:000315447200020 PM 23182989 ER PT J AU Attar, EC Johnson, JL Amrein, PC Lozanski, G Wadleigh, M DeAngelo, DJ Kolitz, JE Powell, BL Voorhees, P Wang, ES Blum, W Stone, RM Marcucci, G Bloomfield, CD Moser, B Larson, RA AF Attar, Eyal C. Johnson, Jeffrey L. Amrein, Philip C. Lozanski, Gerard Wadleigh, Martha DeAngelo, Daniel J. Kolitz, Jonathan E. Powell, Bayard L. Voorhees, Peter Wang, Eunice S. Blum, William Stone, Richard M. Marcucci, Guido Bloomfield, Clara D. Moser, Barry Larson, Richard A. TI Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; FACTOR-KAPPA-B; CELLS; AML; ESCALATION; EXPRESSION; APOPTOSIS; REGIMEN; CANCER; TRIAL AB Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m(2) intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m(2) on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m(2)). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed. Results Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival. Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved tolerable. Further testing of this regimen is planned. J Clin Oncol 31:923-929. (C) 2012 by American Society of Clinical Oncology C1 [Attar, Eyal C.; Amrein, Philip C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wadleigh, Martha; DeAngelo, Daniel J.; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Johnson, Jeffrey L.; Moser, Barry] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Powell, Bayard L.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. [Voorhees, Peter] Univ N Carolina, Chapel Hill, NC USA. [Lozanski, Gerard; Blum, William; Marcucci, Guido; Bloomfield, Clara D.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Kolitz, Jonathan E.] Hofstra North Shore LIJ Sch Med, Lake Success, NY USA. [Wang, Eunice S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Larson, Richard A.] Canc & Leukemia Grp B, Chicago, IL USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Ctr Canc, 100 Blossom, Boston, MA 02114 USA. EM eattar@partners.org RI Blum, William/E-2769-2011; OI Larson, Richard/0000-0001-9168-3203 FU Alliance for Clinical Trials in Oncology [CA35279, CA59518, CA41287, CA31946]; Alliance Statistical Center from the National Cancer Institute [CA33601]; Leukemia Clinical Research Foundation; National Institutes of Health [NIH-5K23CA118419-05]; [CA32291]; [CA03927]; [CA47559]; [CA77658]; [CA101140]; [CA140148]; [CA16058] FX Supported by Grants No. CA32291 (E.C.A., P.C.A.); CA32291 (M.W., D.J.D., R.M.S.); CA33601 (J.L.J., B.K.M.); CA03927 (B.L.P.); CA47559 (P.M.V.); CA77658, CA101140, CA140148, and CA16058 (G.L., W.B., G.M., C.D.B.); CA35279 (J.E.K.); CA59518 (E.S.W.); CA41287 (R.A.L.); CA31946 to the Alliance for Clinical Trials in Oncology; and CA33601 to the Alliance Statistical Center from the National Cancer Institute; by the Leukemia Clinical Research Foundation (G.L., W.B., G.M., C.D.B.); and in part by Grant No. NIH-5K23CA118419-05 (E.C.A.) from the National Institutes of Health. NR 20 TC 37 Z9 40 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2013 VL 31 IS 7 BP 923 EP 929 DI 10.1200/JCO.2012.45.2177 PG 7 WC Oncology SC Oncology GA 097AU UT WOS:000315447200022 PM 23129738 ER PT J AU Trippa, L Lee, EQ Wen, PY Batchelor, TT Cloughesy, T Parmigiani, G Alexander, BM AF Trippa, Lorenzo Lee, Eudocia Q. Wen, Patrick Y. Batchelor, Tracy T. Cloughesy, Timothy Parmigiani, Giovanni Alexander, Brian M. TI Adaptive Randomization Versus Interim Monitoring Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Trippa, Lorenzo; Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Trippa, Lorenzo; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lee, Eudocia Q.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Lee, Eudocia Q.; Wen, Patrick Y.; Batchelor, Tracy T.; Alexander, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA. [Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Trippa, L (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 6 TC 1 Z9 1 U1 0 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2013 VL 31 IS 7 BP 970 EP 971 DI 10.1200/JCO.2012.47.4403 PG 3 WC Oncology SC Oncology GA 097AU UT WOS:000315447200030 PM 23565532 ER PT J AU Chan, JA Kulke, MH AF Chan, Jennifer A. Kulke, Matthew H. TI Bevacizumab and Subtype-Adapted Chemotherapy Backbone in Neuroendocrine Tumors Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID TEMOZOLOMIDE C1 [Chan, Jennifer A.] Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA151532] NR 8 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2013 VL 31 IS 7 BP 977 EP 978 DI 10.1200/JCO.2012.47.0575 PG 3 WC Oncology SC Oncology GA 097AU UT WOS:000315447200037 PM 23565537 ER PT J AU Chiesa-Fuxench, ZC Kim, EJ Schaffer, A Fett, N AF Chiesa-Fuxench, Zelma C. Kim, Ellen J. Schaffer, Andras Fett, Nicole TI Linear lupus panniculitis of the scalp presenting as alopecia along Blaschko's lines: A variant of lupus panniculitis not unique to East Asians SO JOURNAL OF DERMATOLOGY LA English DT Letter C1 [Chiesa-Fuxench, Zelma C.] Univ Puerto Rico, Sch Med, Dept Dermatol, San Juan, PR 00936 USA. [Kim, Ellen J.; Schaffer, Andras; Fett, Nicole] Univ Penn, Dept Dermatol, Sch Med, Philadelphia, PA 19104 USA. [Fett, Nicole] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Fett, N (reprint author), Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM nicole.fett@uphs.upenn.edu NR 4 TC 2 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD MAR PY 2013 VL 40 IS 3 BP 231 EP 232 DI 10.1111/1346-8138.12041 PG 2 WC Dermatology SC Dermatology GA 097JE UT WOS:000315469000023 PM 23252454 ER PT J AU Barnes, DE Boscardin, WJ Landefeld, CS AF Barnes, Deborah E. Boscardin, W. John Landefeld, C. Seth TI Recovery, Dependence or Death After Discharge SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter C1 [Barnes, Deborah E.; Boscardin, W. John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA. [Barnes, Deborah E.; Boscardin, W. John] San Francisco VA Med Ctr, San Francisco, CA USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM Deborah.barnes@ucsf.edu NR 4 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 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2013 VL 28 IS 3 BP 343 EP 343 DI 10.1007/s11606-012-2310-3 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 096WA UT WOS:000315434200006 PM 23435831 ER PT J AU Chang, ET Rose, DE Yano, EM Wells, KB Metzger, ME Post, EP Lee, ML Rubenstein, LV AF Chang, Evelyn T. Rose, Danielle E. Yano, Elizabeth M. Wells, Kenneth B. Metzger, Maureen E. Post, Edward P. Lee, Martin L. Rubenstein, Lisa V. TI Determinants of Readiness for Primary Care-Mental Health Integration (PC-MHI) in the VA Health Care System SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; mental health; depression; collaborative care; implementation; readiness ID COMORBIDITY SURVEY REPLICATION; RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; COLLABORATIVE CARE; QUALITY-IMPROVEMENT; COST-EFFECTIVENESS; ORGANIZATIONAL READINESS; TRANSLATING EVIDENCE; UNITED-STATES; MEDICAL HOME AB Depression management can be challenging for primary care (PC) settings. While several evidence-based models exist for depression care, little is known about the relationships between PC practice characteristics, model characteristics, and the practice's choices regarding model adoption. We examined three Veterans Affairs (VA)-endorsed depression care models and tested the relationships between theoretically-anchored measures of organizational readiness and implementation of the models in VA PC clinics. 1) Qualitative assessment of the three VA-endorsed depression care models, 2) Cross-sectional survey of leaders from 225 VA medium-to-large PC practices, both in 2007. We assessed PC readiness factors related to resource adequacy, motivation for change, staff attributes, and organizational climate. As outcomes, we measured implementation of one of the VA-endorsed models: collocation, Translating Initiatives in Depression into Effective Solutions (TIDES), and Behavioral Health Lab (BHL). We performed bivariate and, when possible, multivariate analyses of readiness factors for each model. Collocation is a relatively simple arrangement with a mental health specialist physically located in PC. TIDES and BHL are more complex; they use standardized assessments and care management based on evidence-based collaborative care principles, but with different organizational requirements. By 2007, 107 (47.5 %) clinics had implemented collocation, 39 (17.3 %) TIDES, and 17 (7.6 %) BHL. Having established quality improvement processes (OR 2.30, [1.36, 3.87], p = 0.002) or a depression clinician champion (OR 2.36, [1.14, 4.88], p = 0.02) was associated with collocation. Being located in a VA regional network that endorsed TIDES (OR 8.42, [3.69, 19.26], p < 0.001) was associated with TIDES implementation. The presence of psychologists or psychiatrists on PC staff, greater financial sufficiency, or greater spatial sufficiency was associated with BHL implementation. Both readiness factors and characteristics of depression care models influence model adoption. Greater model simplicity may make collocation attractive within local quality improvement efforts. Dissemination through regional networks may be effective for more complex models such as TIDES. C1 [Chang, Evelyn T.] VA Greater Los Angeles, Los Angeles, CA 90073 USA. [Rose, Danielle E.; Yano, Elizabeth M.; Lee, Martin L.; Rubenstein, Lisa V.] VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA USA. [Yano, Elizabeth M.; Wells, Kenneth B.; Lee, Martin L.] UCLA Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Wells, Kenneth B.] UCLA Psychiat & Biobehav Sci, Los Angeles, CA USA. [Wells, Kenneth B.; Rubenstein, Lisa V.] RAND, Santa Monica, CA USA. [Metzger, Maureen E.; Post, Edward P.] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Metzger, Maureen E.; Post, Edward P.] Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. [Post, Edward P.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. RP Chang, ET (reprint author), VA Greater Los Angeles, Los Angeles, CA 90073 USA. EM evelyn.chang@va.gov OI Post, Edward/0000-0002-5782-8736 FU VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program [TMP 65-020]; VA HSR&D Service through a Research Career Scientist Award [RCS 05-195]; VA HSRD Project [09-082] FX Funding support provided by VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program (TMP 65-020). Dr. Yano's time was funded by the VA HSR&D Service through a Research Career Scientist Award (Project # RCS 05-195). The project was also supported by VA HSR&D Project # 09-082 (Yano, PI). NR 59 TC 18 Z9 18 U1 1 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2013 VL 28 IS 3 BP 353 EP 362 DI 10.1007/s11606-012-2217-z PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 096WA UT WOS:000315434200010 PM 23054917 ER PT J AU Ring, D AF Ring, David TI First Hand: Kraftskiva SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2013 VL 38A IS 3 BP 562 EP 563 DI 10.1016/j.jhsa.2012.11.021 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 099XW UT WOS:000315660200021 ER PT J AU Aslan, M Concato, J Peduzzi, PN Proctor, SP Schnurr, PP Marx, BP McFall, M Gleason, T Huang, GD Vasterling, JJ AF Aslan, Mihaela Concato, John Peduzzi, Peter N. Proctor, Susan P. Schnurr, Paula P. Marx, Brian P. McFall, Miles Gleason, Theresa Huang, Grant D. Vasterling, Jennifer J. TI Design of "Neuropsychological and Mental Health Outcomes of Operation Iraqi Freedom: A Longitudinal Cohort Study'' SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE posttraumatic stress disorders; brain injuries; traumatic; neuropsychological tests; closed cohort studies; methods ID ADMINISTERED PTSD SCALE; CES-D; DEPLOYMENT; PERSONNEL; VETERANS; WAR AB Objective: This study aimed to describe methodological challenges encountered in designing a follow-up assessment of US Army Soldiers who served in Operation Iraqi Freedom. Study Design and Setting: The Neurocognition Deployment Health Study (NDHS) enrolled 1595 soldiers at 2 military installations, starting in 2003. Prior work compared predeployment and postdeployment assessments among Iraq-deployed and nondeployed soldiers. The current phase, as VA Cooperative Studies Program #566, is collecting follow-up data on participants who were deployed to Iraq or Afghanistan. Specific aims include evaluating the prevalence and course of posttraumatic stress disorder (PTSD), the persistence of previously observed neuropsychological changes, and the relationship of these changes-and traumatic brain injury-to subsequent PTSD. The target sample size is 817 participants, with 200 participants also receiving performance-based neuropsychological assessments. Results: We describe 6 methodological challenges and their implications for longitudinal research among a "closed,'' young, mobile study population: transitioning from cluster-based (battalion) sampling to individual-level sampling; overcoming practical barriers (such as location searches); selecting exposure and outcome measures that combine previously collected and current study data; accounting for loss of an exposed (deployed) versus (nonexposed) nondeployed comparison; determining timing of assessments; and developing a complex statistical analysis plan. Enrollment is ongoing. Conclusions: The study provides unique insights regarding elements of study design and analysis that are relevant to longitudinal research. In particular, the dynamic "real-life'' context of military deployment provides a basis for applying observational methodology to characterize mental health disorders associated with exposure to war-zone deployment and other contexts associated with exposure to extreme stress. C1 [Aslan, Mihaela; Concato, John] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT 06516 USA. [Aslan, Mihaela; Concato, John] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Peduzzi, Peter N.] Yale Univ, Yale Ctr Analyt Sci, New Haven, CT USA. [Peduzzi, Peter N.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Proctor, Susan P.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Proctor, Susan P.] USA, Environm Med Res Inst, Natick, MA 01760 USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. [Schnurr, Paula P.] White River Junction VA Med Ctr, VA Natl Ctr Posttraumat Stress Disorder PTSD, White River Jct, VT USA. [Marx, Brian P.; Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Marx, Brian P.; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Marx, Brian P.; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [McFall, Miles] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [McFall, Miles] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Gleason, Theresa; Huang, Grant D.] US Dept Vet Affairs, Off Res & Dev, NW, Washington, DC USA. RP Aslan, M (reprint author), VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, 950 Campbell Ave,Mailcode 151B, West Haven, CT 06516 USA. EM mihaela.aslan@va.gov FU Department of Veterans Affairs Cooperative Studies Program; Abt SRBI, Inc. FX Supported by the Department of Veterans Affairs Cooperative Studies Program.; The authors thank all the participants in this study. Participants are enrolled by staff at sites in Boston and Seattle, with specific services provided via a contract with Abt SRBI, Inc. The study is managed by the CSP #566 Chair's office at the Boston VA Healthcare System, the VA Clinical Epidemiology Research Center (CERC) at VA Connecticut Healthcare System in West Haven, an Executive Committee, and a Data Monitoring Committee; the entire initiative is overseen by VA Office of Research and Development. In addition to the authors of the paper, the following persons have provided expertise or assistance in the conduct of the study. Boston site: Fabiana Cabral, Meredith Charney, May Chen, Kaitlyn Gorman, Sohyun Han, Darren Holowaka, Heather Kapson, Amy Lawrence, Mary Alice Mills, Nicole Rodier, Paola Rodriguez, and Erin Ulloa. Seattle site: Kate Hoerster, Matthew Jakupcak, David Slagle, David Tice, and Ollie (Richie) Yarbrough. Chair's Office: Molly Franz, Anna Graefe, and Helen MacDonald. West Haven CERC and CSP Coordinating Center: Margaret Antonelli, Donna Cavaliere, Patricia Crutchfield, Maria deAsis, Peter Guarino, Adrienne Hoey, John Ko, Kathy Newvine, Susan O'Neil, Diane Orlando, Thomas Roy, and Joseph Turner. Executive Committee members: Paul Amoroso, Paul Bliese, Charles Hoge, and Theresa O'Connor. Data Monitoring Committee: Haiqun Lin, Scott Orr, Margaret Ryan, Karen Schwab, and Ayumi Shintani. VA Central Office: Timothy O'Leary. CSP Clinical Research Pharmacy Coordinating Center (CSPCRPCC): Clair Haakenson, Darlene Krueger, Amanda Snodgrass, and Kathleen Swanson [Site Monitoring, Auditing and Review Team (SMART)]. NR 28 TC 1 Z9 1 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2013 VL 61 IS 3 BP 569 EP 577 DI 10.231/JIM.0b013e31828407ff PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 097GU UT WOS:000315462800012 PM 23392054 ER PT J AU Ning, MM Lopez, M Sarracino, DA Feeney, K Thayer, M Elia, M Koop, H McMullin, D Demirjian, Z Inglessis-Azuaje, I Silverman, S Dec, GW Palacios, I Lo, EH Buonanno, FS AF Ning, MingMing Lopez, Mary Sarracino, David A. Feeney, Kathleen Thayer, Molly Elia, Mikaela Koop, Hailey McMullin, David Demirjian, Zareh Inglessis-Azuaje, Ignacio Silverman, Scott Dec, G. William Palacios, Igor Lo, Eng H. Buonanno, Ferdinando S. TI Proteomic Profiles in Long Term Follow-up of Patent Foramen Ovale Related Stroke Patients SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Eastern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 16-17, 2013 CL Washington, DC SP Amer Federat Med Res (AFMR) C1 [Ning, MingMing; Lopez, Mary; Sarracino, David A.; Feeney, Kathleen; Thayer, Molly; Elia, Mikaela; Koop, Hailey; McMullin, David; Demirjian, Zareh; Inglessis-Azuaje, Ignacio; Silverman, Scott; Dec, G. William; Palacios, Igor; Lo, Eng H.; Buonanno, Ferdinando S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Prote Res Ctr, Boston, MA 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2013 VL 61 IS 3 BP 671 EP 671 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 097GU UT WOS:000315462800060 ER PT J AU Egyhazi, R Ramakrishnan, P Ning, MM AF Egyhazi, Rachel Ramakrishnan, Pankaja Ning, MingMing TI Opthalmologic Findings Associated with Recurrent Stroke in a Young Adult SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Eastern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 16-17, 2013 CL Washington, DC SP Amer Federat Med Res (AFMR) C1 [Egyhazi, Rachel] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. [Ramakrishnan, Pankaja] Emory Univ, Sch Med, Atlanta, GA USA. [Ning, MingMing] Harvard Univ, Sch Med, Dept Neurol, Cardioneurol Clin,Massachusetts Gen Hosp, 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2013 VL 61 IS 3 BP 675 EP 675 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 097GU UT WOS:000315462800073 ER PT J AU Cao, J Buonanno, FS Feeney, K Elia, M Koop, H McMullin, D Guo, SZ Arai, K Lo, EH Ning, MM AF Cao, Jing Buonanno, Ferdinando S. Feeney, Kathleen Elia, Mikaela Koop, Hailey McMullin, David Guo, Shu-Zhen Arai, Ken Lo, Eng H. Ning, MingMing TI Glyco-proteomic Study of "Cool Therapy" in Global Ischemic Brain Injury Post Cardiac Arrest SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Eastern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 16-17, 2013 CL Washington, DC SP Amer Federat Med Res (AFMR) C1 [Cao, Jing; Buonanno, Ferdinando S.; Feeney, Kathleen; Elia, Mikaela; Koop, Hailey; McMullin, David; Guo, Shu-Zhen; Arai, Ken; Lo, Eng H.; Ning, MingMing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Prote Res Ctr, Boston, MA 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2013 VL 61 IS 3 BP 676 EP 676 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 097GU UT WOS:000315462800076 ER PT J AU Ning, MM Cao, J Lopez, M Sarracino, DA McMullin, D Walleigh, D Sena, D Feeney, K Thayer, M Elia, M Koop, H Buonanno, FS Wang, XY Lo, EH AF Ning, MingMing Cao, Jing Lopez, Mary Sarracino, David A. McMullin, David Walleigh, Diana Sena, Dayse Feeney, Kathleen Thayer, Molly Elia, Mikaela Koop, Hailey Buonanno, Ferdinando S. Wang, Xiaoying Lo, Eng H. TI Plasma Protein Changes after Tissue Plasminogen Activator (tPA) treatment in Acute Ischemic Stroke Patients SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Eastern Regional Meeting of the American-Federation-for-Medical-Research (AFMR) CY APR 16-17, 2013 CL Washington, DC SP Amer Federat Med Res (AFMR) C1 [Ning, MingMing; Cao, Jing; Lopez, Mary; Sarracino, David A.; McMullin, David; Walleigh, Diana; Sena, Dayse; Feeney, Kathleen; Thayer, Molly; Elia, Mikaela; Koop, Hailey; Buonanno, Ferdinando S.; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Prote Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2013 VL 61 IS 3 BP 676 EP 676 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 097GU UT WOS:000315462800077 ER PT J AU Jin, JO Yu, Q AF Jin, Jun-O Yu, Qing TI Systemic administration of TLR3 agonist induces IL-7 expression and IL-7-dependent CXCR3 ligand production in the lung SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE poly I:C; IFN-gamma; M1 macrophage; chemokine; effector T cells; NK cells ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; INTESTINAL EPITHELIAL-CELLS; T-CELLS; INTERLEUKIN-7 RECEPTOR; MACROPHAGE DIFFERENTIATION; HOMEOSTATIC PROLIFERATION; RHEUMATOID-ARTHRITIS; INDEPENDENT PATHWAYS; INTERFERON INDUCTION AB In this study, we tested the hypothesis that systemic administration of TLR3 agonist poly I: C can enhance T cell infiltration of lung through up-regulating IL-7 expression. poly I: C, a synthetic analog of viral dsRNA and a TLR3 agonist, is studied extensively as vaccine adjuvant as a result of its pleotropic immune-stimulatory effects. Here, we show that systemic poly I: C administration induces substantial IL-7 production in the lung in a type 1 IFN- and IFN-gamma-dependent fashion. Blockade of the IL-7R alpha signal with a neutralizing antibody abrogated poly I: C-induced MCP-1 up-regulation, macrophage recruitment, and CXCR3 ligand expression in the lung. Conversely, administration of IL-7 enhances these events, and it does so by enhancing T cell IFN-gamma production. We also show that the initial up-regulation of CXCR3 ligands and infiltration of T cells in the lung are mediated by poly I: C-induced IFN-gamma from NK cells; however, the sustained and optimal CXCR3 ligand expression and T cell infiltration require poly I: C-induced IL-7 and T cell-derived IFN-gamma. In a model of multiorgan inflammation elicited by adoptive transfer of immune cells into RAG1(-/-) mice, we show that poly I: C enhances IL-7 production in the lung and promotes expression of CXCR3 ligands and recruitment of IFN-gamma(+) T cells in an IL-7-dependent fashion. Collectively, these results strongly support our hypothesis and delineate a new mechanism by which poly I: C boosts the T cell immune response in the lung by inducing local IL-7 production, which in turn, enhances T cell-derived IFN-gamma to promote macrophage recruitment, CXCR3 ligand expression, and T cell infiltration. J. Leukoc. Biol. 93: 413-425; 2013. C1 [Jin, Jun-O; Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. RP Yu, Q (reprint author), Forsyth Inst, Dept Immunol, 245 1st St, Cambridge, MA 02142 USA. EM qyu@forsyth.org FU U.S. National Institutes of Health [P30DE020751] FX This study was supported by grants from the U.S. National Institutes of Health (P30DE020751). We thank Dr. D. J. Smith for support and advice in this project. We thank Drs. A. Bhandoola and K. Shortman for critical reading of the manuscript, the Forsyth Institute Animal Facility for maintaining animals, and Biological Resources Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, for providing rhIL-7. NR 71 TC 6 Z9 7 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 2013 VL 93 IS 3 BP 413 EP 425 DI 10.1189/jlb.0712360 PG 13 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 098WL UT WOS:000315579700011 PM 23271706 ER PT J AU Chen, AY Yoon, MK Haugh, S Phan, LT Song, J McCulley, TJ AF Chen, Aiyin Yoon, Michael K. Haugh, Sarah Phan, Laura T. Song, Jonathan McCulley, Timothy J. TI Surgical Management of an Optic Nerve Glioma with Perineural Arachnoidal Gliomatosis Growth Pattern SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID VISUAL PATHWAY; NEUROFIBROMATOSIS; TUMORS AB We describe a vision sparing surgical approach for optic nerve glioma. A 7-year-old girl experienced declining academic performance and social withdrawal attributed to progressive disfiguring proptosis. Three years earlier, she had undergone a limited biopsy, a course of chemotherapy, and orbital radiation therapy for a right optic nerve glioma with perineural arachnoidal gliomatosis (PAG). Because of marked proptosis, another surgery was performed via a lateral orbitotomy. After cutting a window in the thickened dura of the optic nerve, rouge colored spongy tissue was suctioned from the subarachnoid space. Small, more solidified areas were excised with unipolar cautery. Care was taken to avoid identifiable blood vessels and the optic nerve, and approximately 60%-70% of the tumor was removed. The dural window was approximated with interrupted sutures. Postoperatively, there was 9 mm reduction in right proptosis and visual acuity improved to from 20/70 to 20/60. This case illustrates the possibility of debulking optic nerve gliomas without sacrificing vision. It should be stressed that this technique is only applicable to gliomas with PAG and the durability of the surgical benefit is unknown. Journal of Neuro-Ophthalmology 2013; 33:51-53 doi: 10.1097/WNO.0b013e3182745090 (C) 2012 by North American Neuro-Ophthalmology Society C1 [Chen, Aiyin; Haugh, Sarah] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. [Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Phan, Laura T.; Song, Jonathan; McCulley, Timothy J.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Song, Jonathan; McCulley, Timothy J.] King Khalid Eye Specialist Hosp, Riyadh, Saudi Arabia. RP McCulley, TJ (reprint author), Johns Hopkins Sch Med, Wilmer Eye Inst, 600 North Wolfe St,Wilmer 110, Baltimore, MD 21287 USA. EM tmccull5@jhmi.edu FU Research to Prevent Blindness Inc, New York FX Supported in part by an unrestricted grant to the Wilmer Ophthalmological Institute from Research to Prevent Blindness Inc, New York. NR 12 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD MAR PY 2013 VL 33 IS 1 BP 51 EP 53 DI 10.1097/WNO.0b013e3182745090 PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 095MO UT WOS:000315338800015 PM 23149617 ER PT J AU Neimark, MAH Konstas, AA Lee, L Laine, AF Pile-Spellman, J Choi, J AF Neimark, Matthew Aaron Harold Konstas, Angelos Aristeidis Lee, Leslie Laine, Andrew Francis Pile-Spellman, John Choi, Jae TI Brain temperature changes during selective cooling with endovascular intracarotid cold saline infusion: simulation using human data fitted with an integrated mathematical model SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID MODERATE HYPOTHERMIA; ACUTE STROKE; CEREBRAL-ISCHEMIA; CARDIAC-ARREST; FEASIBILITY; INFARCTION; SAFETY; FLOW; AID AB The feasibility of rapid cerebral hypothermia induction in humans with intracarotid cold saline infusion (ICSI) was investigated using a hybrid approach of jugular venous bulb temperature (JVBT) sampling and mathematical modeling of transient and steady state brain temperature distribution. This study utilized both forward mathematical modeling, in which brain temperatures were predicted based on input saline temperatures, and inverse modeling, where brain temperatures were inferred based on JVBT. Changes in ipsilateral anterior circulation territory temperature (IACT) were estimated in eight patients as a result of 10 min of a cold saline infusion of 33 ml/min. During ICSI, the measured JVBT dropped by 0.76 +/- 0.18 degrees C while the modeled JVBT decreased by 0.86 +/- 0.18 degrees C. The modeled IACT decreased by 2.1 +/- 0.23 degrees C. In the inverse model, IACT decreased by 1.9 +/- 0.23 degrees C. The results of this study suggest that mild cerebral hypothermia can be induced rapidly and safely with ICSI in the neuroangiographical setting. The JVBT corrected mathematical model can be used as a non-invasive estimate of transient and steady state cerebral temperature changes. C1 [Neimark, Matthew Aaron Harold] SUNY Downstate, Dept Radiol, Brooklyn, NY USA. [Konstas, Angelos Aristeidis] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, Leslie] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. [Laine, Andrew Francis] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Pile-Spellman, John] Neurol Surg PC, Dept Intervent Radiol, Great Neck, NY USA. [Choi, Jae] Columbia Univ, Dept Neurol, New York, NY USA. RP Neimark, MAH (reprint author), SUNY Downstate, Dept Radiol, 451 Clarkson Ave,Box 47,B Bldg,3rd Floor,Room 330, Brooklyn, NY USA. EM man2003@columbia.edu FU Dana Foundation (Clinical Neuroscience Research Award) FX This study was supported by a grant from the Dana Foundation (Clinical Neuroscience Research Award; JP-S and JC). NR 31 TC 3 Z9 3 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAR PY 2013 VL 5 IS 2 BP 165 EP 171 DI 10.1136/neurintsurg-2011-010150 PG 7 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 095XP UT WOS:000315368600016 PM 22270331 ER PT J AU Dabus, G Pryor, J Spilberg, G Samaniego, EA Nogueira, RG AF Dabus, Guilherme Pryor, Johnny Spilberg, Gabriela Samaniego, Edgar A. Nogueira, Raul G. TI Embolization of intra-axial hypervascular tumors with Onyx: report of three cases SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID PREOPERATIVE ENDOVASCULAR EMBOLIZATION; DURAL ARTERIOVENOUS-FISTULAS; HEMANGIOBLASTOMAS AB Complete surgical resection of intra-axial hypervascular tumors located in the posterior fossa, in particular hemangioblastomas, may be challenging due to tumor. location, mass effect and excessive bleeding. Embolization of these lesions can be done preoperatively or as a palliative measure in patients who are not surgical candidates. Preoperative embolization may reduce intraoperative blood loss, shorten surgical time and increase the chance of a complete resection. However, the safety and effectiveness of this procedure is still a matter of debate. Three cases of intra-axial hypervascular tumors in the posterior fossa (two confirmed hemangioblastomas) that were embolized using a non-adhesive liquid embolic agent (Onyx) are reported. C1 [Dabus, Guilherme; Samaniego, Edgar A.] Baptist Cardiac & Vasc Inst, Dept Neurointervent Surg, Miami, FL USA. [Pryor, Johnny] Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Spilberg, Gabriela] Univ Massachusetts, Dept Radiol, Worcester, MA 01605 USA. [Nogueira, Raul G.] Emory Univ, Dept Neurol, Atlanta, GA 30303 USA. RP Nogueira, RG (reprint author), Emory Univ, Dept Neurol, Atlanta, GA 30303 USA. EM raul.g.nogueira@emory.edu NR 13 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAR PY 2013 VL 5 IS 2 BP 177 EP 180 DI 10.1136/neurintsurg-2011-010212 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 095XP UT WOS:000315368600018 PM 22266792 ER PT J AU Jimenez, R Zhang, BH Joffe, S Nilsson, M Rivera, L Mutchler, J Lathan, C Paulk, ME Prigerson, HG AF Jimenez, Rachel Zhang, Baohui Joffe, Steven Nilsson, Matthew Rivera, Lorna Mutchler, Jan Lathan, Christopher Paulk, M. Elizabeth Prigerson, Holly G. TI Clinical Trial Participation among Ethnic/Racial Minority and Majority Patients with Advanced Cancer: What Factors Most Influence Enrollment? SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID LIFE; BARRIERS; RACE; END; DISPARITIES; CARE AB Background: Studies using administrative data report that racial/ethnic minority patients enroll in clinical trials less frequently than white patients. We studied a cohort of terminally ill cancer patients to determine a) if racial/ethnic minority patients have lower rates of drug trial enrollment than white patients once socioeconomic characteristics are accounted for and b) what factors most influence drug trial enrollment among patients with advanced canceroverall. Methods: Coping with Cancer (CwC) is a National Cancer Institute/National Institute of Mental Health (NCI/NIMH)-funded multisite, prospective, longitudinal study of patients with advanced cancer. Baseline interviews assessed drug trial enrollment as well as socioeconomic characteristics. Logistic regression models estimated associations between drug trial enrollment and baseline characteristics. Stepwise, backward, and subset model selection was applied to select the final model where characteristics significant at a = 0.05 remained in the model. Results: At a median of 4.4 months prior to death, 35 of 358 patients (9.8%) were enrolled in a drug trial. In unadjusted analyses, race/ethnicity, health insurance, performance status, recruitment site, cancer type, preference for life-extending care, and lack of end-of-life care planning were associated (p < 0.05) with enrollment. In multivariable analysis, patient race/ethnicity was not significantly associated with enrollment. Patients who reported not having an end-of-life discussion (adjusted odds ratio [AOR], 0.18; 95% confidence interval [CI] 0.04-0.83) and those not wanting to discuss life expectancy (AOR, 0.31; 95% CI 0.12-0.79) were more likely to be trial enrollees. Conclusion: Patient race/ethnicity was not associated with clinical trial enrollment after adjustment for socioeconomic covariates. Patients with advanced cancer endorsing less engagement in end-of-life planning were more likely to be enrolled in a clinical trial. C1 [Jimenez, Rachel] Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA USA. [Zhang, Baohui; Nilsson, Matthew; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol Res, Boston, MA 02215 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Lathan, Christopher; Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Rivera, Lorna] Univ Massachusetts, Dept Womens Studies, Boston, MA 02125 USA. [Mutchler, Jan] Univ Massachusetts, Program Social & Demog Res, Inst Gerontol, McCormack Grad Sch Policy & Global Studies, Boston, MA 02125 USA. [Paulk, M. Elizabeth] Univ Texas Southwestern Med Sch, Dept Internal Med, Dallas, TX USA. [Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM holly_prigerson@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [U54 CA156732] NR 20 TC 7 Z9 7 U1 0 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAR PY 2013 VL 16 IS 3 BP 256 EP 262 DI 10.1089/jpm.2012.0413 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 097GO UT WOS:000315462200011 PM 23384245 ER PT J AU Anderson, WG Horton, JR Johnson, K Goldstein, NE AF Anderson, Wendy G. Horton, Jay R. Johnson, Kimberly Goldstein, Nathan E. TI Update in Hospice and Palliative Care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID DEMENTIA; TRIAL; PAIN; COMMUNICATION; EFFICACY; LIFE; END C1 [Anderson, Wendy G.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Anderson, Wendy G.] Univ Calif San Francisco, Palliat Care Program, San Francisco, CA 94143 USA. [Horton, Jay R.; Goldstein, Nathan E.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Johnson, Kimberly] Duke Univ, Med Ctr, Ctr Geriatr Res Educ & Clin, VA Med Ctr,Div Geriatr, Durham, NC USA. [Johnson, Kimberly] Duke Univ, Med Ctr, Ctr Geriatr Res Educ & Clin, VA Med Ctr,Ctr Palliat Care, Durham, NC USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Anderson, WG (reprint author), Univ Calif San Francisco, 521 Parnassus Ave,Box 0903, San Francisco, CA 94143 USA. EM Wendy.Anderson@ucsf.edu FU University of California San Francisco Clinical and Translational Science Institute Career Development Program; NIH [5KL2 RR024130-06] FX Dr. Anderson was funded by the University of California San Francisco Clinical and Translational Science Institute Career Development Program, which is supported by NIH grant number 5KL2 RR024130-06. The authors presented these articles for the State of the Science Plenary Session at the Annual Assembly of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association on March 10, 2012, in Denver, Colorado. NR 18 TC 0 Z9 0 U1 1 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAR PY 2013 VL 16 IS 3 BP 314 EP 319 DI 10.1089/jpm.2012.0481 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 097GO UT WOS:000315462200021 ER PT J AU Bouldin, ELD Andresen, EM Dunton, NE Simon, M Waters, TM Liu, MZ Daniels, MJ Mion, LC Shorr, RI AF Bouldin, Erin L. D. Andresen, Elena M. Dunton, Nancy E. Simon, Michael Waters, Teresa M. Liu, Minzhao Daniels, Michael J. Mion, Lorraine C. Shorr, Ronald I. TI Falls Among Adult Patients Hospitalized in the United States: Prevalence and Trends SO JOURNAL OF PATIENT SAFETY LA English DT Article DE accidental falls; epidemiology; hospital units; injuries/epidemiology; databases ID PREVENTING FALLS; INPATIENT FALLS; ACUTE-CARE; INJURIES; CIRCUMSTANCES; SYSTEM AB Objectives: The purpose of this study was to provide normative data on fall prevalence in U. S. hospitals by unit type and to determine the 27-month secular trend in falls before the implementation of the Centers for Medicare and Medicaid Service (CMS) rule, which does not reimburse hospitals for care related to injury resulting from hospital falls. Methods: We used data from the National Database of Nursing Quality Indicators (NDNQI) collected between July 1, 2006, and September 30, 2008, to estimate prevalence and secular trends of falls occurring in adult medical, medical-surgical, and surgical nursing units. More than 88 million patient days (pd) of observation were contributed from 6100 medical, surgical, and medical-surgical nursing units in 1263 hospitals across the United States. Results: A total of 315,817 falls occurred (rate = 3.56 falls/1000 pd) during the study period, of which, 82,332 (26.1%) resulted in an injury (rate = 0.93/1000 pd). Both total fall and injurious fall rates were highest in medical units (fall rate = 4.03/1000 pd; injurious fall rate = 1.08/1000 pd) and lowest in surgery units (fall rate = 2.76/1000 pd; injurious fall rate = 0.67/1000 pd). Falls (0.4% decrease per quarter, P < 0.0001) and injurious falls (1% decrease per quarter, P G 0.0001) both decreased over the 27-month study. Conclusions: In this large sample, fall and injurious fall prevalence varied by nursing unit type in U.S. hospitals. Over the 27-month study, there was a small, but statistically significant, decrease in falls (P G 0.0001) and injurious falls (P < 0.0001). C1 [Bouldin, Erin L. D.] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA. [Bouldin, Erin L. D.; Andresen, Elena M.] Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL USA. [Bouldin, Erin L. D.; Andresen, Elena M.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Epidemiol, Gainesville, FL USA. [Andresen, Elena M.] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97201 USA. [Dunton, Nancy E.] Univ Kansas, Med Ctr, Sch Nursing, Dept Hlth Policy & Management, Kansas City, KS 66103 USA. [Simon, Michael] Univ Southampton, Fac Hlth Sci, Southampton SO9 5NH, Hants, England. [Waters, Teresa M.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Knoxville, TN 37996 USA. [Liu, Minzhao; Daniels, Michael J.] Univ Florida, Dept Stat, Coll Liberal Arts & Sci, Gainesville, FL 32611 USA. [Mion, Lorraine C.] Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. [Shorr, Ronald I.] Malcom Randall VAMC, GRECC, Gainesville, FL 32608 USA. [Shorr, Ronald I.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. RP Shorr, RI (reprint author), Malcom Randall VAMC, GRECC 182, 1601 SW Archer Rd, Gainesville, FL 32608 USA. EM rshorr@ufl.edu RI Simon, Michael/C-5601-2008 OI Simon, Michael/0000-0003-2349-7219 FU NIH/NIA [R01-AG025285, R01-AG033005] FX Grant Support: NIH/NIA R01-AG025285, NIH/NIA R01-AG033005 NR 22 TC 25 Z9 27 U1 0 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1549-8417 J9 J PATIENT SAF JI J. Patient Saf. PD MAR PY 2013 VL 9 IS 1 BP 13 EP 17 DI 10.1097/PTS.0b013e3182699b64 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 096MO UT WOS:000315408600003 PM 23143749 ER PT J AU Kelly, MS Conway, M Wirth, KE Potter-Bynoe, G Billett, AL Sandora, TJ AF Kelly, Matthew S. Conway, Margaret Wirth, Kathleen E. Potter-Bynoe, Gail Billett, Amy L. Sandora, Thomas J. TI Microbiology and Risk Factors for Central Line-Associated Bloodstream Infections Among Pediatric Oncology Outpatients: A Single Institution Experience of 41 Cases SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE catheter infections; pediatric oncology; community-onset CLABSI; neutropenia ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; HICKMAN CATHETERS; SURVEILLANCE; PREVENTION; CANCER; STATISTICS; HEMATOLOGY; MORTALITY; CHILDREN AB Background: Risk factors for central line-associated bloodstream infections (CLABSI) among children with cancer in the outpatient setting remain poorly defined, and the microbiology may differ from hospital-onset CLABSI. Materials and Methods: We conducted a matched case-control study of oncology patients followed at the Dana Farber/Children's Hospital Cancer Center. Cases (N = 41) were patients with CLABSI as per National Healthcare Safety Network criteria who had not been hospitalized in the preceding 48 hours. For each case we randomly selected 2 oncology outpatients with a central venous catheter and a clinic visit within 30 days of the case subject's CLABSI. Multivariate conditional logistic regression models were used to identify independent risk factors for CLABSI. We compared the microbiology to that of 54 hospital-onset CLABSI occurring at our institution during the study period. Results: Independent predictors of community-onset CLABSI included neutropenia in the prior week (odds ratio 17.46; 95% confidence interval, 4.71-64.67) and tunneled externalized catheter (vs. implantable port; odds ratio 10.30; 95% confidence interval, 2.42-43.95). Nonenteric gram-negative bacteria were more frequently isolated from CLABSI occurring among outpatients. Discussion: Pediatric oncology outpatients with recent neutropenia or tunneled externalized catheters are at increased risk of CLABSI. The microbiology of community-onset CLABSI differs from hospital-onset CLABSI. C1 [Kelly, Matthew S.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Conway, Margaret] Boston Childrens Hosp, Med Patient Serv, Boston, MA USA. [Potter-Bynoe, Gail; Sandora, Thomas J.] Boston Childrens Hosp, Boston, MA USA. [Billett, Amy L.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Sandora, Thomas J.] Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. [Sandora, Thomas J.] Boston Childrens Hosp, Dept Med & Lab Med, Boston, MA USA. [Wirth, Kathleen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Billett, Amy L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kelly, MS (reprint author), 3535 Market St,Suite 1300, Philadelphia, PA 19104 USA. EM kellym8@email.chop.edu FU US National Institutes of Health [AI 007433] FX K.E.W. received grant support from the US National Institutes of Health (AI 007433). NR 30 TC 9 Z9 9 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAR PY 2013 VL 35 IS 2 BP E71 EP E76 DI 10.1097/MPH.0b013e3182820edd PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 095TH UT WOS:000315357100007 PM 23412591 ER PT J AU Dionne, KR Zhuang, YH Leser, JS Tyler, KL Clarke, P AF Dionne, Kalen R. Zhuang, Yonghua Leser, J. Smith Tyler, Kenneth L. Clarke, Penny TI Daxx Upregulation within the Cytoplasm of Reovirus-Infected Cells Is Mediated by Interferon and Contributes to Apoptosis SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; DEATH-ASSOCIATED PROTEIN; TRAIL-INDUCED APOPTOSIS; PML ONCOGENIC DOMAINS; N-TERMINAL KINASE; GENE-EXPRESSION; JNK ACTIVATION; KAPPA-B; INTERACTING PROTEIN; SIGNALING PATHWAYS AB Reovirus infection is a well-characterized experimental system for the study of viral pathogenesis and antiviral immunity within the central nervous system (CNS). We have previously shown that c-Jun N-terminal kinase (JNK) and the Fas death receptor each play a role in neuronal apoptosis occurring in reovirus-infected brains. Death-associated protein 6 (Daxx) is a cellular protein that mechanistically links Fas signaling to JNK signaling in several models of apoptosis. In the present study, we demonstrate that Daxx is upregulated in reovirus-infected brain tissue through a type I interferon-mediated mechanism. Daxx upregulation is limited to brain regions that undergo reovirus-induced apoptosis and occurs in the cytoplasm and nucleus of neurons. Cytoplasmic Daxx is present in Fas-expressing cells during reovirus encephalitis, suggesting a role for Daxx in Fas-mediated apoptosis following reovirus infection. Further, in vitro expression of a dominant negative form of Daxx (DN-Daxx), which binds to Fas but which does not transmit downstream signaling, inhibits apoptosis of reovirus-infected cells. In contrast, in vitro depletion of Daxx results in increased expression of caspase 3 and apoptosis, suggesting that Daxx plays an antiapoptotic role in the nucleus. Overall, these data imply a regulatory role for Daxx in reovirus-induced apoptosis, depending on its location in the nucleus or cytoplasm. C1 [Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado, Med Scientist Training Program, Aurora, CO USA. [Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado, Neurosci Program, Denver, CO 80202 USA. [Dionne, Kalen R.; Zhuang, Yonghua; Leser, J. Smith; Tyler, Kenneth L.; Clarke, Penny] Univ Colorado, Dept Neurol, Denver, CO 80202 USA. [Tyler, Kenneth L.] Univ Colorado, Dept Med, Denver, CO USA. [Tyler, Kenneth L.] Univ Colorado, Dept Microbiol, Denver, CO 80202 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Clarke, P (reprint author), Univ Colorado, Dept Neurol, Denver, CO 80202 USA. EM Penny.Clarke@UCDenver.edu RI Zhuang, Yonghua/A-2946-2013; OI Zhuang, Yonghua/0000-0002-1822-2395; Tyler, Kenneth/0000-0003-3294-5888 FU VA Merit Grant [1/01BX000963]; institutional Medical Scientist Training Program training grant [T32GM008497]; National Research Service Award for Individual Predoctoral MD/PhD Fellows [F30NS071630]; [RO1NS076512] FX This work was supported by RO1NS076512 (K.L.T) and VA Merit Grant 1/01BX000963 (K.L.T). K.R.D. was supported by an institutional Medical Scientist Training Program training grant (T32GM008497) and a National Research Service Award for Individual Predoctoral MD/PhD Fellows (F30NS071630). NR 75 TC 11 Z9 11 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2013 VL 87 IS 6 BP 3447 EP 3460 DI 10.1128/JVI.02324-12 PG 14 WC Virology SC Virology GA 095QD UT WOS:000315348500043 PM 23302889 ER PT J AU Pretorius, E Vermeulen, N Bester, J Lipinski, B AF Pretorius, Etheresia Vermeulen, Natasha Bester, Janette Lipinski, Boguslaw TI Novel Use of Scanning Electron Microscopy for Detection of Iron-Induced Morphological Changes in Human Blood SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE purified fibrinogen; human plasma; novel laboratory model; electron microscopy; iron ID FIBRINOGEN; COAGULATION AB Fibrinogen is key to the maintenance of hemostasis and is an acute phase protein that is part of the coagulation cascade of proteins. It plays a fundamental role in inflammation, particularly as indicator for a proinflammatory state and is a prominent marker for developing vascular inflammatory diseases. The ultrastructure of fibrin nets can be studied using scanning electron microscopy (SEM) with the addition of thrombin to plasma. In inflammatory conditions such as thromboembolic ischemic stroke and diabetes, the fibrin networks are changed to from dense matted fibrin deposits (DMDs) instead of typical netlike appearance. Similar DMDs can also be induced with the addition of FeCl2 and FeCl3. Importantly, the iron-induced DMDs look similar to those from patients with prothrombotic conditions. Excessive or misplaced tissue iron now is recognized to pose a substantial health risk. The current research therefore investigates the establishment of a laboratory fibrinogen model to study that might mimic fibrin fiber generation that is achieved using plasma from healthy and diseased individuals. Furthermore, to determine whether the addition of iron to purified fibrinogen will show DMDs and whether hydrophilic agents can prevent them. We conclude that SEM is a very effective tool for the visualization of circulatory consequences of the interaction of iron-induced hydroxyl radicals with human fibrinogen. Furthermore, this novel fibrinogen model provides a convenient method to study the interactions of the intramolecular and intermolecular hydrophobic forces responsible for the maintenance of the tertiary structure of native fibrin(ogen) and the prevention of iron-induced DMDs formation by hydrophilic agents. Microsc. Res. Tech. 76:268271, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Pretorius, Etheresia; Vermeulen, Natasha; Bester, Janette] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa. [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag X323, ZA-0007 Arcadia, South Africa. EM resia.pretorius@up.ac.za OI Pretorius, Etheresia/0000-0002-9108-2384 NR 14 TC 9 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD MAR PY 2013 VL 76 IS 3 BP 268 EP 271 DI 10.1002/jemt.22163 PG 4 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 097RD UT WOS:000315490300009 PM 23280783 ER PT J AU Pugh, TJ Morozova, O Attiyeh, EF Asgharzadeh, S Wei, JS Auclair, D Carter, SL Cibulskis, K Hanna, M Kiezun, A Kim, J Lawrence, MS Lichenstein, L McKenna, A Pedamallu, CS Ramos, AH Shefler, E Sivachenko, A Sougnez, C Stewart, C Ally, A Birol, I Chiu, R Corbett, RD Hirst, M Jackman, SD Kamoh, B Khodabakshi, AH Krzywinski, M Lo, A Moore, RA Mungall, KL Qian, J Tam, A Thiessen, N Zhao, YJ Cole, KA Diamond, M Diskin, SJ Mosse, YP Wood, AC Ji, LY Sposto, R Badgett, T London, WB Moyer, Y Gastier-Foster, JM Smith, MA Auvil, JMG Gerhard, DS Hogarty, MD Jones, SJM Lander, ES Gabriel, SB Getz, G Seeger, RC Khan, J Marra, MA Meyerson, M Maris, JM AF Pugh, Trevor J. Morozova, Olena Attiyeh, Edward F. Asgharzadeh, Shahab Wei, Jun S. Auclair, Daniel Carter, Scott L. Cibulskis, Kristian Hanna, Megan Kiezun, Adam Kim, Jaegil Lawrence, Michael S. Lichenstein, Lee McKenna, Aaron Pedamallu, Chandra Sekhar Ramos, Alex H. Shefler, Erica Sivachenko, Andrey Sougnez, Carrie Stewart, Chip Ally, Adrian Birol, Inanc Chiu, Readman Corbett, Richard D. Hirst, Martin Jackman, Shaun D. Kamoh, Baljit Khodabakshi, Alireza Hadj Krzywinski, Martin Lo, Allan Moore, Richard A. Mungall, Karen L. Qian, Jenny Tam, Angela Thiessen, Nina Zhao, Yongjun Cole, Kristina A. Diamond, Maura Diskin, Sharon J. Mosse, Yael P. Wood, Andrew C. Ji, Lingyun Sposto, Richard Badgett, Thomas London, Wendy B. Moyer, Yvonne Gastier-Foster, Julie M. Smith, Malcolm A. Auvil, Jaime M. Guidry Gerhard, Daniela S. Hogarty, Michael D. Jones, Steven J. M. Lander, Eric S. Gabriel, Stacey B. Getz, Gad Seeger, Robert C. Khan, Javed Marra, Marco A. Meyerson, Matthew Maris, John M. TI The genetic landscape of high-risk neuroblastoma SO NATURE GENETICS LA English DT Article ID ACTIVATING MUTATIONS; SOMATIC MUTATIONS; NOONAN-SYNDROME; CHILDHOOD-CANCER; SOLID TUMORS; ALK KINASE; AMPLIFICATION; LEUKEMIA; DISEASE; PTPN11 AB Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers. C1 [Pugh, Trevor J.; Auclair, Daniel; Carter, Scott L.; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S.; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H.; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA USA. [Pugh, Trevor J.; Ramos, Alex H.; London, Wendy B.; Meyerson, Matthew] Harvard Univ, Sch Med, Boston, MA USA. [Pugh, Trevor J.; Hanna, Megan; Pedamallu, Chandra Sekhar; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Morozova, Olena; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D.; Hirst, Martin; Jackman, Shaun D.; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A.; Mungall, Karen L.; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Jones, Steven J. M.; Marra, Marco A.] Univ British Columbia, British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1M9, Canada. [Morozova, Olena; Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Attiyeh, Edward F.; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Hogarty, Michael D.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Attiyeh, Edward F.; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Hogarty, Michael D.; Maris, John M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Attiyeh, Edward F.; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Hogarty, Michael D.; Maris, John M.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asgharzadeh, Shahab; Ji, Lingyun; Sposto, Richard; Seeger, Robert C.] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Asgharzadeh, Shahab; Ji, Lingyun; Sposto, Richard; Seeger, Robert C.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Asgharzadeh, Shahab; Ji, Lingyun; Sposto, Richard; Seeger, Robert C.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Wei, Jun S.; Badgett, Thomas; Khan, Javed] NIH, Pediat Oncol Branch, Oncogen Sect, Ctr Canc Res, Gaithersburg, MD USA. [London, Wendy B.] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA. [London, Wendy B.] Childrens Oncol Grp, Boston, MA USA. [Moyer, Yvonne; Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Biopathol Ctr, Columbus, OH USA. [Moyer, Yvonne; Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Auvil, Jaime M. Guidry; Gerhard, Daniela S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. RP Marra, MA (reprint author), Univ British Columbia, British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1M9, Canada. EM mmarra@bcgsc.ca; matthew_meyerson@dfci.harvard.edu; maris@chop.edu RI Tang, Macy/B-9798-2014; Khan, Javed/P-9157-2014; Cole, Kristina/M-3922-2015; Hirst, Martin/B-7684-2016; Jones, Steven/C-3621-2009; Marra, Marco/B-5987-2008; Birol, Inanc/G-5440-2011 OI Khan, Javed/0000-0002-5858-0488; Birol, Inanc/0000-0003-0950-7839 FU US National Institutes of Health [CA98543, CA98413, RC1MD004418, CA124709, CA060104]; National Human Genome Research Institute grant [U54HG003067]; National Cancer Institute, US National Institutes of Health [HHSN261200800001E]; Canadian Institutes of Health Research Fellowship; Roman M. Babicki Fellowship in Medical Research at the University of British Columbia; Canada Research Chair in Genome Science; Giulio D'Angio Endowed Chair; Alex's Lemonade Stand Foundation; Arms Wide Open Foundation; Cookies for Kids Foundation FX We thank the Children's Oncology Group for the collection and annotation of samples for this study, and all TARGET co-investigators for scientific support of this project. Funding was provided by US National Institutes of Health grants CA98543 and CA98413 to the Children's Oncology Group, RC1MD004418 to the TARGET consortium, CA124709 (J.M.M.) and CA060104 (R.C.S.) and National Human Genome Research Institute grant U54HG003067 (E.S.L., D.A., S.B.G., G.G. and M.M.), as well as a contract from the National Cancer Institute, US National Institutes of Health (HHSN261200800001E). Additional support included a Canadian Institutes of Health Research Fellowship (T.J.P.), a Roman M. Babicki Fellowship in Medical Research at the University of British Columbia (O.M.), the Canada Research Chair in Genome Science (M.A.M.), the Giulio D'Angio Endowed Chair (J.M.M.), the Alex's Lemonade Stand Foundation (J.M.M.), the Arms Wide Open Foundation (J.M.M.) and the Cookies for Kids Foundation (J.M.M.). We thank E. Nickerson, S. Charmer, K. Novik, C. Suragh and R. Roscoe for project management support. We also thank the staff of the Genome Sciences Centre Biospecimen Core, Library Construction, Sequencing and Bioinformatics teams, and the staff of the Broad Institute Biological Samples, Genome Sequencing and Genetic Analysis Platforms for their expertise in genomic processing of samples, and generating the sequencing data used in this analysis. NR 70 TC 228 Z9 230 U1 8 U2 67 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 2013 VL 45 IS 3 BP 279 EP 284 DI 10.1038/ng.2529 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 099ZP UT WOS:000315664800011 PM 23334666 ER PT J AU Brastianos, PK Horowitz, PM Santagata, S Jones, RT McKenna, A Getz, G Ligon, KL Palescandolo, E Van Hummelen, P Ducar, MD Raza, A Sunkavalli, A MacConaill, LE Stemmer-Rachamimov, AO Louis, DN Hahn, WC Dunn, IF Beroukhim, R AF Brastianos, Priscilla K. Horowitz, Peleg M. Santagata, Sandro Jones, Robert T. McKenna, Aaron Getz, Gad Ligon, Keith L. Palescandolo, Emanuele Van Hummelen, Paul Ducar, Matthew D. Raza, Alina Sunkavalli, Ashwini MacConaill, Laura E. Stemmer-Rachamimov, Anat O. Louis, David N. Hahn, William C. Dunn, Ian F. Beroukhim, Rameen TI Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations SO NATURE GENETICS LA English DT Article ID BASAL-CELL CARCINOMAS; NF2; PATHWAY; CANCER; MEDULLOBLASTOMA; COMPLEXITY; LANDSCAPE; PATTERNS; TUMORS AB Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of all meningiomas(1), but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas had simple genomes, with fewer mutations, rearrangements and copy-number alterations than reported in other tumors in adults. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements, including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers in an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets. C1 [Brastianos, Priscilla K.; Jones, Robert T.; Van Hummelen, Paul; Ducar, Matthew D.; Raza, Alina; Sunkavalli, Ashwini; MacConaill, Laura E.; Hahn, William C.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brastianos, Priscilla K.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Brastianos, Priscilla K.; Horowitz, Peleg M.; Santagata, Sandro; Ligon, Keith L.; Stemmer-Rachamimov, Anat O.; Louis, David N.; Hahn, William C.; Dunn, Ian F.; Beroukhim, Rameen] Harvard Univ, Sch Med, Boston, MA USA. [Brastianos, Priscilla K.; Horowitz, Peleg M.; McKenna, Aaron; Getz, Gad; Hahn, William C.; Dunn, Ian F.; Beroukhim, Rameen] Broad Inst MIT & Harvard, Boston, MA USA. [Horowitz, Peleg M.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Horowitz, Peleg M.; Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Santagata, Sandro; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jones, Robert T.; Palescandolo, Emanuele; Van Hummelen, Paul; Ducar, Matthew D.; Raza, Alina; Sunkavalli, Ashwini; MacConaill, Laura E.; Hahn, William C.; Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Stemmer-Rachamimov, Anat O.; Louis, David N.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Beroukhim, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu; idunn@partners.org; rameen@broadinstitute.org OI Brastianos, Priscilla/0000-0003-4470-8425; Horowitz, Peleg/0000-0002-5177-1783 FU Brain Science Foundation; Pediatric Low-Grade Astrocytoma Foundation; American Brain Tumor Association; Conquer Cancer Foundation Young Investigator Award; US National Institutes of Health (NIH) [K08 CA122833, K08 NS064168, K12 CA090354-11]; US Department of Defense grant [W81XWE-12-1-0136] FX The authors would like to thank M. Lawrence, N. Stransky, M. Imielinski, K. Cibulskis, S. Carter, C. Stewart, C.-Z. Zhang, Y. Drier, S. Schumacher and B. Tabak for their assistance with genomic analyses; P. Wen, O. Al-Mefty, T. Batchelor, B. Reisler, M. Johnson, W. Richards and J. Kim for their assistance with tissue acquisition; and A. Pisarek-Horowitz, S.A. Horowitz, G. Bergthold and C.H. Brastianos for critical review of the manuscript. This work was supported by the Brain Science Foundation (I.F.D., P.K.B., R.B. and S.S.), the Pediatric Low-Grade Astrocytoma Foundation (R.B. and W.C.H.), the American Brain Tumor Association (P.K.B.), a Conquer Cancer Foundation Young Investigator Award (P.K.B.), US National Institutes of Health (NIH) grants K08 CA122833 (R.B.), K08 NS064168 (S.S.) and K12 CA090354-11 (P.K.B.), and US Department of Defense grant W81XWE-12-1-0136 (P.M.H.). NR 40 TC 123 Z9 126 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2013 VL 45 IS 3 BP 285 EP 289 DI 10.1038/ng.2526 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 099ZP UT WOS:000315664800012 PM 23334667 ER PT J AU Kirby, A Gnirke, A Jaffe, DB Baresova, V Pochet, N Blumenstiel, B Ye, C Aird, D Stevens, C Robinson, JT Cabili, MN Gat-Viks, I Kelliher, E Daza, R DeFelice, M Hulkova, H Sovova, J Vylet'al, P Antignac, C Guttman, M Handsaker, RE Perrin, D Steelman, S Sigurdsson, S Scheinman, SJ Sougnez, C Cibulskis, K Parkin, M Green, T Rossin, E Zody, MC Xavier, RJ Pollak, MR Alper, SL Lindblad-Toh, K Gabriel, S Hart, PS Regev, A Nusbaum, C Kmoch, S Bleyer, AJ Lander, ES Daly, MJ AF Kirby, Andrew Gnirke, Andreas Jaffe, David B. Baresova, Veronika Pochet, Nathalie Blumenstiel, Brendan Ye, Chun Aird, Daniel Stevens, Christine Robinson, James T. Cabili, Moran N. Gat-Viks, Irit Kelliher, Edward Daza, Riza DeFelice, Matthew Hulkova, Helena Sovova, Jana Vylet'al, Petr Antignac, Corinne Guttman, Mitchell Handsaker, Robert E. Perrin, Danielle Steelman, Scott Sigurdsson, Snaevar Scheinman, Steven J. Sougnez, Carrie Cibulskis, Kristian Parkin, Melissa Green, Todd Rossin, Elizabeth Zody, Michael C. Xavier, Ramnik J. Pollak, Martin R. Alper, Seth L. Lindblad-Toh, Kerstin Gabriel, Stacey Hart, P. Suzanne Regev, Aviv Nusbaum, Chad Kmoch, Stanislav Bleyer, Anthony J. Lander, Eric S. Daly, Mark J. TI Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing SO NATURE GENETICS LA English DT Article ID GENETIC DIAGNOSIS; CHROMOSOME 1Q21; REFINEMENT; LINKAGE; LOCUS; MCKD1; MAP AB Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (similar to 1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing. C1 [Kirby, Andrew; Gnirke, Andreas; Jaffe, David B.; Pochet, Nathalie; Blumenstiel, Brendan; Ye, Chun; Aird, Daniel; Stevens, Christine; Robinson, James T.; Cabili, Moran N.; Gat-Viks, Irit; Daza, Riza; DeFelice, Matthew; Guttman, Mitchell; Handsaker, Robert E.; Perrin, Danielle; Steelman, Scott; Sigurdsson, Snaevar; Sougnez, Carrie; Cibulskis, Kristian; Parkin, Melissa; Green, Todd; Rossin, Elizabeth; Zody, Michael C.; Xavier, Ramnik J.; Lindblad-Toh, Kerstin; Gabriel, Stacey; Regev, Aviv; Nusbaum, Chad; Lander, Eric S.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Kirby, Andrew; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Baresova, Veronika; Hulkova, Helena; Sovova, Jana; Vylet'al, Petr; Kmoch, Stanislav] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Prague, Czech Republic. [Pochet, Nathalie] Univ Ghent VIB, Dept Plant Syst Biol, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium. [Cabili, Moran N.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Gat-Viks, Irit] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Antignac, Corinne] INSERM, U983, Paris, France. [Antignac, Corinne] Univ Paris 05, Inst Imagine, Paris, France. [Antignac, Corinne] Hop Necker Enfants Malad, Assistance Publ Hop Paris, Dept Genet, Paris, France. [Handsaker, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Scheinman, Steven J.] Commonwealth Med Coll, Scranton, PA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Ctr Study Inflammatory Bowe, Boston, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Pollak, Martin R.; Alper, Seth L.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Pollak, Martin R.; Alper, Seth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab Uppsala, Uppsala, Sweden. [Hart, P. Suzanne] NHGRI, Off Clin Director, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Bleyer, Anthony J.] Wake Forest Sch Med, Sect Nephrol, Winston Salem, NC 27106 USA. RP Bleyer, AJ (reprint author), Wake Forest Sch Med, Sect Nephrol, Winston Salem, NC 27106 USA. EM ableyer@wfubmc.edu; lander@broadinstitute.org; mjdaly@atgu.mgh.harvard.edu RI Vyletal, Petr/F-4771-2017 OI Vyletal, Petr/0000-0002-9357-1237 FU Carlos Slim Health Institute; Intramural Research Program of the US NIH, National Human Genome Research Institute (NHGRI); Charles University [PRVOUK-P24/LF1/3, UNCE 204011]; Ministry of Education [LH12015, NT13116-4/2012]; US NIH grant [DK34854]; Human Frontier Science Program, Alon; Israeli Centers of Research Excellence (I-CORE); Edmond J. Safra Center for Bioinformatics at Tel Aviv University; Ministry of Health of the Czech Republic FX We thank T.L. Hatte for reagent use. We thank D. Altshuler, T. Carter and J. Schlondorff for useful discussions and M. Cortes, M. Ilzarbe and M. Betancourt for helpful project management. We also thank F. Letendre, M. Coole, R.P. Frere, C. Bonnet, L. Mulrain, N. Norbui and H. Arachchi for Sanger sequencing. This work was conducted as part of the Slim Initiative for Genomic Medicine, a joint United States-Mexico project funded by the Carlos Slim Health Institute. This research was supported in part by the Intramural Research Program of the US NIH, National Human Genome Research Institute (NHGRI). S.K., H.H., J.S. and V.B. were funded by Charles University programs PRVOUK-P24/LF1/3 and UNCE 204011, and their work was supported by grants LH12015 and NT13116-4/2012 from the Ministry of Education and the Ministry of Health of the Czech Republic. S.L.A. was supported by US NIH grant DK34854 (The Harvard Digestive Diseases Center). N.P. is a Broad Fellow of the Broad Institute and a postdoctoral research fellow of the Fund for Scientific Research-Flanders (FWO Vlaanderen, Belgium). I.G.-V. was supported by the Human Frontier Science Program, Alon, the Israeli Centers of Research Excellence (I-CORE) and the Edmond J. Safra Center for Bioinformatics at Tel Aviv University. NR 19 TC 50 Z9 53 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2013 VL 45 IS 3 BP 299 EP 303 DI 10.1038/ng.2543 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 099ZP UT WOS:000315664800015 PM 23396133 ER PT J AU Bloecker, K Guermazi, A Wirth, W Benichou, O Kwoh, CK Hunter, DJ Englund, M Resch, H Eckstein, F AF Bloecker, K. Guermazi, A. Wirth, W. Benichou, O. Kwoh, C. K. Hunter, D. J. Englund, M. Resch, H. Eckstein, F. CA OAI Investigators TI Tibial coverage, meniscus position, size and damage in knees discordant for joint space narrowing - data from the Osteoarthritis Initiative SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Meniscus; Joint space narrowing; Radiographic osteoarthritis; Magnetic resonance imaging; Tibial coverage ID CARTILAGE LOSS; LATERAL MENISCUS; RADIOGRAPHIC FEATURES; ARTICULAR-CARTILAGE; MRI; ASSOCIATION; EXTRUSION; VOLUME; OAI; SEGMENTATION AB Introduction: Meniscal extrusion is thought to be associated with less meniscus coverage of the tibial surface, but the association of radiographic disease stage with quantitative measures of tibial plateau coverage is unknown. We therefore compared quantitative and semi-quantitative measures of meniscus position and morphology in individuals with bilateral painful knees discordant on medial joint space narrowing (mJSN). Methods: A sample of 60 participants from the first half (2,678 cases) of the Osteoarthritis Initiative cohort fulfilled the inclusion criteria: bilateral frequent pain, Osteoarthritis Research Society International (OARSI) mJSN grades 1-3 in one, no-JSN in the contra-lateral (CL), and no lateral JSN in either knee (43 unilateral mJSN1; 17 mJSN2/3; 22 men, 38 women, body mass index (BMI) 31.3 +/- 3.9 kg/m(2)). Segmentation and three-dimensional quantitative analysis of the tibial plateau and meniscus, and semiquantitative evaluation of meniscus damage (magnetic resonance imaging (MRI) osteoarthritis knee score = MOAKS) was performed using coronal 3T MR images (MPR DESSwe and intermediate-weighted turbo spin echo (IW-TSE) images). CL knees were compared using paired t-tests (between-knee, within-person design). Results: Medial tibial plateau coverage was 36 +/- 9% in mJSN1 vs 45 +/- 8% in CL no-JSN knees, and was 31 +/- 9% in mJSN2/3 vs 46 +/- 6% in no-JSN knees (both P < 0.001). mJSN knees showed greater meniscus extrusion and damage (MOAKS), but no significant difference in meniscus volume. No significant differences in lateral tibial coverage, lateral meniscus morphology or position were observed. Conclusions: Knees with medial JSN showed substantially less medial tibial plateau coverage by the meniscus. We suggest that the less meniscal coverage, i.e., less mechanical protection may be a reason for greater rates of cartilage loss observed in JSN knees. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Bloecker, K.; Wirth, W.; Eckstein, F.] Paracelsus Med Univ, Inst Anat & Musculoskeletal Res, A-5020 Salzburg, Austria. [Bloecker, K.; Resch, H.] Paracelsus Med Univ, Dept Traumatol & Sports Injuries, A-5020 Salzburg, Austria. [Guermazi, A.] Boston Univ, Sch Med, Dept Radiol, Quantitat Imaging Ctr, Boston, MA 02118 USA. [Guermazi, A.] BICL LLC, Boston, MA USA. [Wirth, W.; Eckstein, F.] Chondrometrics GmbH, Ainring, Germany. [Benichou, O.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Kwoh, C. K.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA. [Kwoh, C. K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hunter, D. J.] Univ Sydney, Royal N Shore Hosp, Dept Rheumatol, Sydney, NSW 2006, Australia. [Hunter, D. J.] Univ Sydney, Kolling Inst, Sydney, NSW 2006, Australia. [Englund, M.] Lund Univ, Dept Orthoped, Lund, Sweden. [Englund, M.] Boston Univ, Sch Med, Clin Epidemiol Res &Training Unit, Boston, MA 02118 USA. RP Bloecker, K (reprint author), Paracelsus Med Univ, Inst Anat & Musculoskeletal Res, Strubergasse 21, A-5020 Salzburg, Austria. EM katja.bloecker@pmu.ac.at RI Wirth, Wolfgang/C-8724-2011; Englund, Martin/J-7245-2012 OI Wirth, Wolfgang/0000-0002-2297-8283; Englund, Martin/0000-0003-3320-2437 FU OAI [N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, N01-AR-2-2262]; National Institutes of Health, a branch of the Department of Health and Human Services; Pfizer, Inc.; Novartis Pharmaceuticals Corporation; Merck Research Laboratories; GlaxoSmithKline; Foundation for the National Institutes of Health; Paracelsus Medical University (PMU) Forschungsfond [PMU FFF R-12702/036/BLO]; Australian Research Council Future Fellowship; Swedish Research Council; Royal Physiographic Society in Lund and Koch Foundations FX We would like to thank the OAI participants, OAI investigators and OAI Clinical Center's staff for generating this publicly available image data set. The study and image acquisition were supported by the Osteoarthritis Initiative (OAI). The OAI is a public-private partnership comprised of five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators. Private funding partners include Pfizer, Inc.; Novartis Pharmaceuticals Corporation; Merck Research Laboratories; and GlaxoSmithKline. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This manuscript has received the approval of the OAI Publications Committee based on a review of its scientific content and data interpretation. The image analysis was supported by the Paracelsus Medical University (PMU) Forschungsfond (PMU FFF R-12702/036/BLO).; David Hunter is funded by an Australian Research Council Future Fellowship. Martin Englund is funded by Swedish Research Council, the Royal Physiographic Society in Lund, King Gustav 80-Year Birthday Fund and Koch Foundations. NR 44 TC 24 Z9 24 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD MAR PY 2013 VL 21 IS 3 BP 419 EP 427 DI 10.1016/j.joca.2012.11.015 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 098MA UT WOS:000315552200003 PM 23220556 ER PT J AU Lo, MS Lee, GM Gunawardane, N Burchett, SK Lachenauer, CS Lehmann, LE AF Lo, Mindy S. Lee, Grace M. Gunawardane, Nilanthi Burchett, Sandra K. Lachenauer, Catherine S. Lehmann, Leslie E. TI The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy SO PEDIATRIC TRANSPLANTATION LA English DT Article DE stem cell transplantation; solid organ transplantation; malignancy; immunocompromised; adenovirus; respiratory syncytial virus ID RESPIRATORY VIRAL-INFECTIONS; SYNCYTIAL VIRUS-INFECTIONS; IMMUNE FUNCTION; RECIPIENTS; CHILDREN AB RVIs are a significant cause of morbidity and mortality in immunocompromised children. We analyzed the characteristics and outcomes of infection by four respiratory viruses (RSV, adenovirus, influenza, and parainfluenza) treated at a pediatric tertiary care hospital in a retrospective cohort of patients who had received cancer chemotherapy, hematopoietic stem cell, or SOT. A total of 208 infections were studied among 166 unique patients over a time period of 19932006 for transplant recipients, and 20002005 for patients with cancer. RSV was the most common respiratory virus identified. There were 17 (10% of all patients) deaths overall, of which 12 were at least partly attributed to the presence of a RVI. In multivariate models, LRT symptoms in the absence of upper respiratory symptoms on presentation (OR 10.2 [2.3, 45.7], p=0.002) and adenoviral infection (OR 3.7 [1.1, 12.6], p=0.034) were significantly associated with poor outcome, defined as death or disability related to RVI. All of the deaths occurred in patients who had received either solid organ or HSCT. There were no infections resulting in death or disability in the cancer chemotherapy group. C1 [Lo, Mindy S.] Boston Childrens Hosp, Div Immunol, Dept Med, Boston, MA USA. [Lo, Mindy S.; Lee, Grace M.; Burchett, Sandra K.; Lachenauer, Catherine S.; Lehmann, Leslie E.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Grace M.; Burchett, Sandra K.; Lachenauer, Catherine S.] Boston Childrens Hosp, Div Infect Dis, Dept Med, Boston, MA USA. [Lee, Grace M.] Harvard Pilgrim Hlth Care Inst, Ctr Child Hlth Care Studies, Dept Populat Med, Boston, MA USA. [Gunawardane, Nilanthi] Northwestern Univ, Chicago, IL 60611 USA. [Lehmann, Leslie E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Lehmann, LE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM leslie_lehmann@dfci.harvard.edu FU Pediatric Transplant Center and Pediatric Oncology Division at Children's Hospital FX We gratefully acknowledge the support of the Pediatric Transplant Center and Pediatric Oncology Division at Children's Hospital. Specifically, we thank Betsy Blume, Deborah Boyer, Susan Chi, William Harmon, Maureen Jonas, Heung Bae Kim, Lewis Silverman, and others who contributed departmental records. We also acknowledge Yvette Maxwell for medical records support, and Pamela Butler and Denise Simon for help with database construction and data cleaning. NR 19 TC 13 Z9 13 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD MAR PY 2013 VL 17 IS 2 BP 133 EP 143 DI 10.1111/petr.12022 PG 11 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 097IK UT WOS:000315467000014 PM 23228170 ER PT J AU Reusch, JEB Bridenstine, M Regensteiner, JG AF Reusch, Jane E. B. Bridenstine, Mark Regensteiner, Judith G. TI Type 2 diabetes mellitus and exercise impairment SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE Diabetes; Exercise capacity; Vascular; Endothelial function; Diastolic dysfunction ID ALL-CAUSE MORTALITY; LOW CARDIORESPIRATORY FITNESS; UPTAKE KINETIC RESPONSES; LIFE-STYLE INTERVENTION; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; DIASTOLIC DYSFUNCTION; OXYGEN-UPTAKE AB Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study. C1 [Reusch, Jane E. B.] Denver VA Med Ctr, Denver, CO 80220 USA. [Reusch, Jane E. B.; Bridenstine, Mark] Univ Colorado, Sch Med, Div Endocrinol, Aurora, CO 80045 USA. [Regensteiner, Judith G.] Univ Colorado, Sch Med, Div Gen Internal Med & Cardiol, Aurora, CO 80045 USA. [Reusch, Jane E. B.; Regensteiner, Judith G.] Univ Colorado, Sch Med, Dept Med, Ctr Womens Hlth Res, Aurora, CO 80045 USA. RP Reusch, JEB (reprint author), Denver VA Med Ctr, Clermont St, Denver, CO 80220 USA. EM Jane.Reusch@ucdenver.edu FU NCATS NIH HHS [UL1 TR000154]; NHLBI NIH HHS [P01 HL014985, T32 HL007171]; NICHD NIH HHS [K12 HD057022]; NIDDK NIH HHS [R01 DK064741] NR 87 TC 26 Z9 27 U1 0 U2 31 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 EI 1573-2606 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD MAR PY 2013 VL 14 IS 1 BP 77 EP 86 DI 10.1007/s11154-012-9234-4 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 098SC UT WOS:000315568000010 PM 23299658 ER PT J AU Nayagam, BA Edge, AS Needham, K Hyakumura, T Leung, J Nayagam, DAX Dottori, M AF Nayagam, Bryony A. Edge, Albert S. Needham, Karina Hyakumura, Tomoko Leung, Jessie Nayagam, David A. X. Dottori, Mirella TI An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants SO STEM CELLS AND DEVELOPMENT LA English DT Article ID SPIRAL-GANGLION NEURONS; EMBRYONIC STEM-CELLS; PRIMARY AUDITORY NEURONS; INNER-EAR DEVELOPMENT; HAIR-CELLS; SENSORY NEURONS; MOLECULAR-BASIS; DIFFERENTIATION; NEUROTROPHINS; EXPRESSION AB In mammals, the sensory hair cells and auditory neurons do not spontaneously regenerate and their loss results in permanent hearing impairment. Stem cell therapy is one emerging strategy that is being investigated to overcome the loss of sensory cells after hearing loss. To successfully replace auditory neurons, stem cell-derived neurons must be electrically active, capable of organized outgrowth of processes, and of making functional connections with appropriate tissues. We have developed an in vitro assay to test these parameters using cocultures of developing cochlear explants together with neural progenitors derived from human embryonic stem cells (hESCs). We found that these neural progenitors are electrically active and extend their neurites toward the sensory hair cells in cochlear explants. Importantly, this neurite extension was found to be significantly greater when neural progenitors were predifferentiated toward a neural crest-like lineage. When grown in coculture with hair cells only (denervated cochlear explants), stem cell-derived processes were capable of locating and growing along the hair cell rows in an en passant-like manner. Many presynaptic terminals (synapsin 1-positive) were observed between hair cells and stem cell-derived processes in vitro. These results suggest that differentiated hESC-derived neural progenitors may be useful for developing therapies directed at auditory nerve replacement, including complementing emerging hair cell regeneration therapies. C1 [Nayagam, Bryony A.; Needham, Karina; Hyakumura, Tomoko] Univ Melbourne, Dept Otolaryngol, Parkville, Vic 3052, Australia. [Nayagam, Bryony A.; Leung, Jessie; Dottori, Mirella] Univ Melbourne, Ctr Neurosci, Parkville, Vic 3052, Australia. [Nayagam, Bryony A.; Nayagam, David A. X.] Bion Inst, East Melbourne, Australia. [Edge, Albert S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab, Boston, MA USA. [Leung, Jessie; Dottori, Mirella] Univ Melbourne, Dept Anat & Neurosci, Parkville, Vic 3052, Australia. [Nayagam, David A. X.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RP Nayagam, BA (reprint author), Univ Melbourne, Dept Otolaryngol, Royal Victorian Eye & Ear Hosp, Level 2,32 Gisborne St, East Melbourne, Vic 3002, Australia. EM b.nayagam@unimelb.edu.au; mdottori@unimelb.edu.au OI Nayagam, Bryony/0000-0003-1069-6059 FU National Health and Medical Research Council of Australia; Garnett Passe and Rodney Williams Memorial Foundation; Friedreich Ataxia Research Association; University of Melbourne: Department of Otolaryngology; University of Melbourne: Department of Pharmacology; University of Melbourne: Centre for Neuroscience; Royal Victorian Eye and Ear Hospital FX The authors would like to thank Dr. Aurore Brugeaud for her assistance teaching the early postnatal cochlear denervation dissection, and Ms. Ricki Minter and Ms Rachael Sheridan for their technical laboratory support. We also thank Professors David Ryugo, Ed Rubel, Remy Pujol, and Peter Thorne for helpful discussions regarding the interpretation of experimental data and Dr. Clare Parish for her collaboration and provision of reagents. We gratefully acknowledge financial support from the following organizations: the National Health and Medical Research Council of Australia, the Garnett Passe and Rodney Williams Memorial Foundation, the Friedreich Ataxia Research Association, the University of Melbourne: Departments of Otolaryngology, Pharmacology and the Centre for Neuroscience, and the Royal Victorian Eye and Ear Hospital. NR 57 TC 10 Z9 10 U1 1 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD MAR PY 2013 VL 22 IS 6 BP 901 EP 912 DI 10.1089/scd.2012.0082 PG 12 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 098YC UT WOS:000315584000007 PM 23078657 ER PT J AU Patterson, AL Zhang, L Arango, NA Teixeira, J Pru, JK AF Patterson, Amanda L. Zhang, Ling Arango, Nelson A. Teixeira, Jose Pru, James K. TI Mesenchymal-to-Epithelial Transition Contributes to Endometrial Regeneration Following Natural and Artificial Decidualization SO STEM CELLS AND DEVELOPMENT LA English DT Article ID INSULIN-PRODUCING CELLS; MULLERIAN DUCT; STEM-CELLS; MOUSE MODEL; PROGRESSION; REGRESSION; DISEASE; GROWTH; DIFFERENTIATION; IDENTIFICATION AB Despite being a histologically dynamic organ, mechanisms coordinating uterine regeneration during the menstrual/estrous cycle and following parturition are poorly understood. In the current study, we hypothesized that endometrial epithelial tissue regeneration is accomplished, in part, by mesenchymal-to-epithelial transition (MET). To test this hypothesis, fate mapping studies were completed using a double transgenic (Tg) reporter strain, Amhr2-Cre; Rosa26-Stop(fl/fl-EYFP) (i.e., flox-stop EYFP reporter). EYFP expression was observed in Mullerian duct mesenchyme-derived stroma and myometrium, but not epithelia in young and peripubertal double Tg female mice. However, mosaic EYFP expression was observed in epithelia of double Tg mice after parturition. To ensure the observed epithelial EYFP expression was not due to leaky Amhr2 promoter activity, resulting in aberrant Cre expression, transgenic mice expressing LacZ under the control of the Amhr2 promoter (Amhr2-LacZ) were used to monitor beta-galactosidase (beta-Gal) activity within the uterus. beta-Gal activity was not detected in luminal or glandular epithelia regardless of age, reproductive status, or degree of damage incurred within the uterus. Lastly, a unique population of transitional cells was identified that expressed the epithelial cell marker, pan-cytokeratin, and the stromal cell marker, vimentin. These cells localized predominantly to the regeneration zone in the mesometrial region of the endometrium. These findings suggest a previously unappreciated role for MET in endometrial regeneration and have important implications for proliferative diseases of the endometrium such as endometriosis. C1 [Patterson, Amanda L.; Pru, James K.] Washington State Univ, Dept Anim Sci, Ctr Reprod Biol, Sch Mol Biosci, Pullman, WA 99164 USA. [Zhang, Ling; Teixeira, Jose] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA USA. [Arango, Nelson A.] Massachusetts Gen Hosp, Pediat Surg Res Lab, Dept Surg, Boston, MA 02114 USA. [Arango, Nelson A.] Harvard Univ, Sch Med, Boston, MA USA. RP Pru, JK (reprint author), Washington State Univ, Dept Anim Sci, Ctr Reprod Biol, Sch Mol Biosci, Pullman, WA 99164 USA. EM jpru@wsu.edu OI Teixeira, Jose/0000-0002-6438-5064 FU Vincent Memorial Research Funds; NIH [HD066297] FX This work was supported in part by Vincent Memorial Research Funds and NIH HD066297. Submitted material will be presented at the 45th annual Society for the Study of Reproduction conference. NR 48 TC 16 Z9 20 U1 1 U2 22 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD MAR PY 2013 VL 22 IS 6 BP 964 EP 974 DI 10.1089/scd.2012.0435 PG 11 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 098YC UT WOS:000315584000012 PM 23216285 ER PT J AU Harris, RD Javitt, MC Glanc, P Brown, DL Dubinsky, T Harisinghani, MG Khati, NJ Kim, YB Mitchell, DG Pandharipande, PV Pannu, HK Podrasky, AE Royal, HD Shipp, TD Siegel, CL Simpson, L Wall, DJ Wong-You-Cheong, JJ Zelop, CM AF Harris, Robert D. Javitt, Marcia C. Glanc, Phyllis Brown, Douglas L. Dubinsky, Theodore Harisinghani, Mukesh G. Khati, Nadia J. Kim, Young Bae Mitchell, Donald G. Pandharipande, Pari V. Pannu, Harpreet K. Podrasky, Ann E. Royal, Henry D. Shipp, Thomas D. Siegel, Cary Lynn Simpson, Lynn Wall, Darci J. Wong-You-Cheong, Jade J. Zelop, Carolyn M. TI ACR Appropriateness Criteria (R) Clinically Suspected Adnexal Mass SO ULTRASOUND QUARTERLY LA English DT Article DE appropriateness criteria; color doppler sonography; transvaginal ultrasound; adnexal masses; ovarian cysts; ovarian malignancy ID 3-DIMENSIONAL POWER DOPPLER; LOGISTIC-REGRESSION MODELS; OVARIAN-CANCER; POSTMENOPAUSAL WOMEN; DIFFERENTIAL-DIAGNOSIS; SONOGRAPHIC FINDINGS; PELVIC MASSES; GRAY-SCALE; CA 125; ULTRASOUND AB Adnexal masses are a common problem clinically and imaging-wise, and transvaginal US (TVUS) is the first-line imaging modality for assessing them in the vast majority of patients. The findings of US, however, should be correlated with the history and laboratory tests, as well as any patient symptoms. Simple cysts are uniformly benign, and most warrant no further interrogation or treatment. Complex cysts carry more significant implications, and usually engender serial ultrasound(s), with a minority of cases warranting a pelvic MRI. Morphological analysis of adnexal masses with gray-scale US can help narrow the differential diagnosis. Spectral Doppler analysis has not proven useful in most well-performed studies. However, the use of color Doppler sonography adds significant contributions to differentiating between benign and malignant masses and is recommended in all cases of complex masses. Malignant masses generally demonstrate neovascularity, with abnormal branching vessel morphology. Optimal sonographic evaluation is achieved by using a combination of gray-scale morphologic assessment and color or power Doppler imaging to detect flow within any solid areas. The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Javitt, Marcia C.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Brown, Douglas L.; Wall, Darci J.] Mayo Clin, Rochester, MN USA. [Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Khati, Nadia J.] George Washington Univ Hosp, Washington, DC USA. [Kim, Young Bae] Tufts Med Ctr, Boston, MA USA. [Kim, Young Bae] Soc Gynecol Oncologists, Chicago, IL USA. [Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Pandharipande, Pari V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pannu, Harpreet K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Podrasky, Ann E.] Baptist Hosp Miami, South Miami Ctr Women & Infants, Miami, FL USA. [Royal, Henry D.; Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Royal, Henry D.] Soc Nucl Med, Reston, VA 20190 USA. [Shipp, Thomas D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shipp, Thomas D.; Simpson, Lynn; Zelop, Carolyn M.] Amer Coll Obstetricians & Gynecologists, Boston, MA USA. [Simpson, Lynn] Columbia Univ, New York, NY USA. [Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zelop, Carolyn M.] Valley Hosp, Ridgewood, NJ USA. RP Harris, RD (reprint author), Dartmouth Hitchcock Clin, Dept Radiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM rdh@hitchcock.org NR 45 TC 5 Z9 5 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 J9 ULTRASOUND Q JI Ultrasound Q. PD MAR PY 2013 VL 29 IS 1 BP 79 EP 86 DI 10.1097/RUQ.0b013e3182814d9b PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 097BQ UT WOS:000315449400010 PM 23358212 ER PT J AU Nakabayashi, M Xie, WL Buckle, G Bubley, G Ernstoff, MS Walsh, W Morganstern, DE Kantoff, PW Taplin, ME AF Nakabayashi, Mari Xie, Wanling Buckle, Geoffrey Bubley, Glenn Ernstoff, Marc S. Walsh, William Morganstern, Daniel E. Kantoff, Philip W. Taplin, Mary-Ellen TI Long-term Follow-up of a Phase II Trial of Chemotherapy Plus Hormone Therapy for Biochemical Relapse After Definitive Local Therapy for Prostate Cancer SO UROLOGY LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; EARLY BREAST-CANCER; RADICAL PROSTATECTOMY; DOCETAXEL; MEN; ESTRAMUSTINE; MITOXANTRONE; PROGRESSION; PREDNISONE; RECURRENCE AB OBJECTIVE To evaluate long-term follow-up of a phase II trial of chemohormonal therapy in 62 men with prostate cancer biochemical relapse (BR). METHODS Treatment was 4 cycles of docetaxel (70 mg/m(2)) every 3 weeks and estramustine 280 mg three times a day (days 1-5) followed by 15 months of goserelin acetate/bicalutamide. The primary endpoint was the proportion with prostate-specific antigen (PSA) <0.1 with recovered testosterone 5 years after completion of therapy. Secondary endpoints included time to progression (TTP), time to reinitiate androgen deprivation therapy (ADT), the proportion with castration-resistant prostate cancer (CRPC), and overall survival (OS). RESULTS Median follow-up was 8.6 years (range 1.3-11.1 years). At 5 year follow-up, 7 patients (11%) had PSA <0.1 (5 undetectable); 8 (13%) had PSA >0.1 but without reinitiation of ADT (median PSA 0.37). Of the 15 (24%) men without reinitiation of ADT, and 14 have recovered testosterone to normal range. Median TTP for the complete cohort was 35.0 months (95% confidence interval [CI] 31.7-39.2). Baseline PSA <3.0 ng/dL, no prior ADT, and prostatectomy (vs radiation) were associated with longer TTP (P = .0001, P = .0055, and P = .0398, respectively). At the time of analysis, 42 men (68%) had restarted ADT, 23 men had CRPC (37%), and 11 (18%) had chemotherapy. Median time to reinitiation of ADT was 32.6 months (range 0-107.6 months). Median OS has not been reached; there were 15 deaths. CONCLUSION Chemotherapy plus ADT for BR resulted in durable (>5 years) complete responses (<0.1 ng/mL) in 7 men (11%). Twenty-four percent of men have not re-initiated ADT 5 years from completion of protocol therapy. UROLOGY 81: 611-616, 2013. (c) 2013 Elsevier Inc. C1 Lank Ctr Genitourinary Oncol, Div Med Oncol, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Norris Cotton Canc Ctr, Lebanon, NH USA. UMass Mem Med Ctr, Worcester, MA USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, Dept Med, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM mary_taplin@dfci.harvard.edu FU Sanofi-Aventis; Fairweather Foundation; Sally and Michael Fairweather Fund; Uribe Family Fund FX Supported by a grant from Sanofi-Aventis and funding from the Fairweather Foundation, Sally and Michael Fairweather Fund, and Uribe Family Fund (to Mary-Ellen Taplin). NR 16 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAR PY 2013 VL 81 IS 3 BP 611 EP 616 DI 10.1016/j.urology.2012.12.025 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 098EX UT WOS:000315530800037 PM 23452809 ER PT J AU Oliva, E Prat, J Young, RH AF Oliva, Esther Prat, Jaime Young, Robert H. TI Dr. Robert E. Scully: a tribute OBITUARY SO VIRCHOWS ARCHIV LA English DT Biographical-Item C1 [Oliva, Esther; Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. [Prat, Jaime] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain. [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 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD MAR PY 2013 VL 462 IS 3 BP 255 EP 256 DI 10.1007/s00428-012-1364-2 PG 2 WC Pathology SC Pathology GA 099RR UT WOS:000315639400001 PM 23344925 ER EF