FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Richardson, PG Mark, TM Lacy, MQ AF Richardson, Paul G. Mark, Tomer M. Lacy, Martha Q. TI Pomalidomide: New immunomodulatory agent with potent antiproliferative effects SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Pomalidomide; Multiple myeloma; Immunomodulatory agent ID REFRACTORY MULTIPLE-MYELOMA; LENALIDOMIDE PLUS DEXAMETHASONE; IN-VIVO; COMBINATION THERAPY; THALIDOMIDE ANALOGS; CYTOKINE PRODUCTION; CELL-FUNCTION; INHIBIT; DRUGS; CC-4047 AB New treatment options are urgently needed for patients with relapsed multiple myeloma (MM) who are refractory to thalidomide, lenalidomide, and bortezomib therapy. Pomalidomide, a second-generation immunomodulatory agent, has been shown-to exert direct antiproliferative actions on MM cells, effects on the bone-marrow microenvironment, and immunomodulation. In phase I clinical trials, pomalidomide has demonstrated promising response rates in patients with relapsed and/or refractory MM, with manageable toxicity. In phase II trials pomalidomide, 2-4 mg/daily, given continuously or on days 1-21 of a 28-day cycle, in combination with dexamethasone, has been associated with high quality and durable clinical responses in patients who are refractory to lenalidomide, bortezomib, or both. Pomalidomide appears to be well tolerated; hematologic toxicities are the most commonly reported adverse events and peripheral neuropathy is rare. Phase III trials are currently underway to determine the optimal dose and combination regimen of pomalidomide in the treatment of MM. (C) 2013 Published by Elsevier Ireland Ltd. C1 [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mark, Tomer M.] New York Presbyterian Hosp, Div Hematol & Med Oncol, Dept Med, Weill Cornell Med Coll,Cornell Med Ctr, New York, NY USA. [Lacy, Martha Q.] Mayo Clin, Div Hematol, Coll Med, Rochester, MN USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu FU Celgene Corporation FX We thank Shanthi Jayawardena, PhD, and Eva Polk, PhD and Grace Tjon, PhD (Excerpta Medica), for linguistic improvement of the manuscript. Editorial support in the preparation of this manuscript was funded by Celgene Corporation. The authors were fully responsible for all content and editorial decisions for this manuscript. NR 48 TC 14 Z9 14 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD OCT 1 PY 2013 VL 88 SU 1 BP S36 EP S44 DI 10.1016/j.critrevonc.2013.02.001 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 218TI UT WOS:000324455000005 PM 23786844 ER PT J AU Lysy, PA Weir, GC Bonner-Weir, S AF Lysy, Philippe A. Weir, Gordon C. Bonner-Weir, Susan TI Making beta Cells from Adult Cells Within the Pancreas SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetes; Pancreas; Replication; Progenitors; Transdifferentiation; beta cells; Adult cells ID MESENCHYMAL STEM-CELLS; MOLECULE GLUCOKINASE ACTIVATOR; CLINICAL ISLET TRANSPLANTATION; IN-VIVO; MOUSE PANCREAS; DUCT CELLS; PROGENITOR CELLS; EPIGENETIC REGULATION; EXOCRINE PANCREAS; GLUCOSE-TOLERANCE AB Cell therapy is currently considered as a potential therapeutic alternative to traditional treatments of diabetes. Islet and whole pancreas transplantations provided the proof-of-concept of glucose homeostasis restoration after replenishment of the deficiency of beta cells responsible for the disease. Current limitations of these procedures have led to the search for strategies targeting replication of pre-existing beta cells or transdifferentiation of progenitors and adult cells. These investigations revealed an unexpected plasticity towards beta cells of adult cells residing in pancreatic epithelium (eg, acinar, duct, and alpha cells). Here we discuss recent developments in beta-cell replication and beta-cell transdifferentiation of adult epithelial pancreatic cells, with an emphasis on techniques with a potential for clinical translation. C1 [Lysy, Philippe A.] Inst Rech Expt & Clin, Pole Pediat, B-1200 Brussels, Belgium. [Weir, Gordon C.; Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Harvard Stem Cell Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, R01 DK044523] NR 105 TC 19 Z9 19 U1 0 U2 22 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD OCT PY 2013 VL 13 IS 5 BP 695 EP 703 DI 10.1007/s11892-013-0400-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 216AH UT WOS:000324252700013 PM 23925431 ER PT J AU Berg, AT Caplan, R Baca, CB Vickrey, BG AF Berg, Anne T. Caplan, Rochelle Baca, Christine B. Vickrey, Barbara G. TI Early-onset epilepsy, cognition, and behaviour: continuity and challenge Reply SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Letter ID MRI AB Please also see the reply to this letter by . C1 [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, Chicago, IL USA. [Berg, Anne T.] Northwest Mem Feinberg Sch Med, Dept Pediat, Chicago, IL USA. [Caplan, Rochelle] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Baca, Christine B.; Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Baca, Christine B.; Vickrey, Barbara G.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. RP Berg, AT (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, Chicago, IL USA. EM atberg@luriechildrens.org FU NINDS NIH HHS [R37 NS031146, R01 NS031146] NR 5 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD OCT PY 2013 VL 55 IS 10 BP 964 EP 965 DI 10.1111/dmcn.12203 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 213OK UT WOS:000324067100017 PM 23889464 ER PT J AU Ghidei, L Simone, MJ Salow, MJ Zimmerman, KM Paquin, AM Skarf, LM Kostas, TRM Rudolph, JL AF Ghidei, Luwam Simone, Mark J. Salow, Marci J. Zimmerman, Kristin M. Paquin, Allison M. Skarf, Lara M. Kostas, Tia R. M. Rudolph, James L. TI Aging, Antiretrovirals, and Adherence: A Meta Analysis of Adherence among Older HIV-Infected Individuals SO DRUGS & AGING LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEDICATION ADHERENCE; ADVANCED AGE; THERAPY; ADULTS; NONADHERENCE; METAANALYSIS; HIV/AIDS; RESPONSES; OUTCOMES AB Introduction Older adults are generally considered to be at greater risk for medication non-adherence due to factors such as medication complexity, side effects, cost, and cognitive decline. However, this generalization may not apply to older adults with human immunodeficiency virus (HIV). Regardless of age, suboptimal adherence to antiretroviral therapy (ART) can lead to increased viral load, immunosuppression, drug-resistant viral strains, co-morbidities, and opportunistic infections. Understanding trends of adherence to ART among older adults is critical, especially as the population of people living with HIV grows older. Objectives The purpose of this systematic review and meta-analysis is to determine if older individuals with HIV are less likely to be non-adherent to antiretroviral therapy than younger individuals with HIV. Design A systematic search in PubMed, Embase, and PsycINFO was conducted to identify peer-reviewed articles evaluating adherence to ART in older adults. Two independent reviewers screened abstracts, applied inclusion criteria, and appraised study quality. The bibliographies of qualifying studies were searched. Data were abstracted from studies by two independent authors. Meta-analyses were conducted, and adherence levels were reported as the relative risk of non-adherence in older individuals compared to younger individuals. Results The systematic search yielded 1,848 abstracts. Twelve studies met full inclusion criteria. The overall meta-analysis found that older age reduced risk for non-adherence by 27 % (relative risk (RR) 0.72, 95 % confidence interval (CI) 0.64-0.82). Studies assessing both short-term and long-term adherence demonstrated a significant reduction in non-adherence among older patients (RR 0.75, 95 % CI 0.64-0.87 and RR 0.65, 95 % CI 0.50-0.85, respectively). Conclusions Older adults with HIV have a reduced risk for non-adherence to ART than their younger counterparts. Future studies should seek to elucidate contributing factors of adherence among older individuals with HIV. C1 [Ghidei, Luwam] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Simone, Mark J.; Kostas, Tia R. M.; Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Simone, Mark J.; Skarf, Lara M.; Kostas, Tia R. M.; Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Salow, Marci J.; Paquin, Allison M.; Skarf, Lara M.; Kostas, Tia R. M.; Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. [Salow, Marci J.; Zimmerman, Kristin M.; Paquin, Allison M.] VA Boston Healthcare Syst, Dept Pharm, Boston, MA 02130 USA. [Zimmerman, Kristin M.] Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM james.rudolph@va.gov FU HRSA Geriatric Academic Career Award [K01HP23811]; NIH [T35-AG038027-02]; VA Rehabilitation Research Career Development Award; VA Patient Safety Center of Inquiry award; T21 alternative to non-institutional long term care grant FX This work was funded by Dr Simone's HRSA Geriatric Academic Career Award Grant No. K01HP23811 and the NIH T35-AG038027-02 grant awarded to Dr Rudolph and Ms Ghidei. Dr Kostas is partially supported by a John A. Hartford Center of Excellence Award. Dr Rudolph is supported by a VA Rehabilitation Research Career Development Award and a VA Patient Safety Center of Inquiry award. Drs Kostas, Salow, and Rudolph receive funding from a T21 alternative to non-institutional long term care grant. Drs Salow, Paquin, Skarf, Kostas, and Rudolph are employees of the Veterans Health Administration. The views expressed are those of the authors, and do not reflect the official policies of the Veterans Health Administration or U.S. Government. NR 50 TC 25 Z9 26 U1 0 U2 13 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD OCT PY 2013 VL 30 IS 10 BP 809 EP 819 DI 10.1007/s40266-013-0107-7 PG 11 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 219FY UT WOS:000324492800005 PM 23959913 ER PT J AU Barrett, LF AF Barrett, Lisa Feldman TI Psychological Construction: The Darwinian Approach to the Science of Emotion SO EMOTION REVIEW LA English DT Article DE Darwin; emotion; evolution; psychological construction ID INDIVIDUAL-DIFFERENCES; BASIC EMOTIONS; NATURAL KINDS; BRAIN; EXPERIENCE; INFANTS; ANGER; APPRAISAL; CATEGORIZATION; DETERMINANTS AB Psychological construction constitutes a different paradigm for the scientific study of emotion when compared to the current paradigm that is inspired by faculty psychology. This new paradigm is more consistent with the post-Darwinian conceptual framework in biology that includes a focus on (a) population thinking (vs. typologies), (b) domain-general core systems (vs. physical essences), and (c) constructive analysis (vs. reductionism). Three psychological construction approaches (the OCC model, the iterative reprocessing model, and the conceptual act theory) are discussed with respect to these ideas. C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. EM l.barrett@neu.edu NR 76 TC 40 Z9 40 U1 8 U2 44 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1754-0739 J9 EMOT REV JI Emot. Rev. PD OCT PY 2013 VL 5 IS 4 BP 379 EP 389 DI 10.1177/1754073913489753 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 210LD UT WOS:000323833700007 ER PT J AU Pati, S Kumaraswamy, VM Deep, A Chung, SS Plueger, M Kiyota, G Treiman, DM AF Pati, Sandipan Kumaraswamy, Vishakhadatta M. Deep, A. Chung, S. S. Plueger, M. Kiyota, G. Treiman, D. M. TI Characteristics of falls in the epilepsy monitoring unit: A retrospective study SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy monitoring unit; Safety; Fall; Risk assessment ID INPATIENT FALLS; SAFETY AB Falls are an important adverse event in an epilepsy monitoring unit (EMU). We identified patterns of falls in an EMU and compared them with risk factors for inpatient falls. Twenty-six patients with 26 falls (2.3% of admissions) in the EMU were compared with 50 general neurology inpatients with 56 falls over a 4-year period. In the EMU, the majority (62%) of falls happened during the first 3 days of admission, mostly in the bathroom (74%), in patients with a normal mental status (77%). Most general inpatients fell after the third day (64%), inside their rooms (68%), and had an altered mental status before the fall (68%). All 26 EMU patients were identified as high risk at admission, in spite of which falls were not prevented. We outline these differences between EMU patients and general inpatients and highlight the practice gap in preventing falls in an EMU. (C) 2013 Elsevier Inc. All rights reserved. C1 [Pati, Sandipan; Deep, A.; Chung, S. S.; Plueger, M.; Kiyota, G.; Treiman, D. M.] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ USA. [Kumaraswamy, Vishakhadatta M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Pati, S (reprint author), Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, 55 Fruit St, Boston, MA 02114 USA. EM spati@partners.org NR 11 TC 5 Z9 5 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2013 VL 29 IS 1 BP 1 EP 3 DI 10.1016/j.yebeh.2013.06.013 PG 3 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 215WJ UT WOS:000324241300001 PM 23911351 ER PT J AU Mehrotra, P Croft, L Day, HR Perencevich, EN Pineles, L Harris, AD Weingart, SN Morgan, DJ AF Mehrotra, Preeti Croft, Lindsay Day, Hannah R. Perencevich, Eli N. Pineles, Lisa Harris, Anthony D. Weingart, Saul N. Morgan, Daniel J. TI Effects of Contact Precautions on Patient Perception of Care and Satisfaction: A Prospective Cohort Study SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HOSPITALIZED-PATIENTS; ADVERSE EVENTS; INFECTION-CONTROL; DEPRESSION; US AB OBJECTIVE. Contact precautions decrease healthcare worker-patient contact and may impact patient satisfaction. To determine the association between contact precautions and patient satisfaction, we used a standardized interview for perceived issues with care. DESIGN. Prospective cohort study of inpatients, evaluated at admission and on hospital days 3, 7, and 14 (until discharged). At each point, patients underwent a standardized interview to identify perceived problems with care. After discharge, the standardized interview and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey were administered by telephone. Responses were recorded, transcribed, and coded by 2 physician reviewers. PARTICIPANTS. A total of 528 medical or surgical patients not admitted to the intensive care unit. RESULTS. A total of 528 patients were included in the primary analysis, of whom 104 (20%) perceived some issue with their care. On multivariable logistic regression, contact precautions were independently associated with a greater number of perceived concerns with care (odds ratio, 2.05 [95% confidence interval, 1.31-3.21]; P < .01), including poor coordination of care (P = .02) and a lack of respect for patient needs and preferences (P = .001). Eighty-eight patients were included in the secondary analysis of HCAHPS. Patients under contact precautions did not have different HCAHPS scores than those not under contact precautions (odds ratio, 1.79 [95% confidence interval, 0.64-5.00]; P = .27). CONCLUSIONS. Patients under contact precautions were more likely to perceive problems with their care, especially poor coordination of care and a lack of respect for patient preferences. C1 [Mehrotra, Preeti; Croft, Lindsay; Day, Hannah R.; Pineles, Lisa; Harris, Anthony D.; Morgan, Daniel J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Perencevich, Eli N.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Perencevich, Eli N.] Iowa City VA, Iowa City, IA USA. [Harris, Anthony D.; Morgan, Daniel J.] VA Maryland Hlth Care Syst, Baltimore, MD USA. [Weingart, Saul N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weingart, Saul N.] Harvard Univ, Sch Med, Boston, MA USA. RP Mehrotra, P (reprint author), Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM preeti.mehrotra@childrens.harvard.edu FU [1 K08 HS18111-01 AHRQ]; [VA HSRD IIR 09-099]; [1 K24 5K24A1079040-02 NIH] FX 1 K08 HS18111-01 AHRQ (to D.J.M.), VA HSRD IIR 09-099 (to E.N.P.), and 1 K24 5K24A1079040-02 NIH (to A.D.H.). NR 18 TC 14 Z9 15 U1 5 U2 12 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT 1 PY 2013 VL 34 IS 10 BP 1087 EP 1093 DI 10.1086/673143 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 213LH UT WOS:000324058200008 PM 24018926 ER PT J AU Legrand, M Januzzi, JL Mebazaa, A AF Legrand, Matthieu Januzzi, James L., Jr. Mebazaa, Alexandre TI Critical research on biomarkers: what's new? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID ACUTE KIDNEY INJURY; GELATINASE-ASSOCIATED LIPOCALIN; RESPIRATORY-DISTRESS; NATRIURETIC PEPTIDE; TRIAL; DIAGNOSIS; ACCURACY; URINE C1 [Legrand, Matthieu; Mebazaa, Alexandre] Hop St Louis, AP HP, Hop Univ St Louis Lariboisiere, Dept Anesthesiol & Crit Care, F-75010 Paris, France. [Legrand, Matthieu; Mebazaa, Alexandre] Hop St Louis, AP HP, Hop Univ St Louis Lariboisiere, SMUR, F-75010 Paris, France. [Legrand, Matthieu; Mebazaa, Alexandre] Hop St Louis, AP HP, Hop Univ St Louis Lariboisiere, Burn Ctr, F-75010 Paris, France. [Legrand, Matthieu; Mebazaa, Alexandre] Univ Paris Diderot, F-75475 Paris, France. [Legrand, Matthieu; Mebazaa, Alexandre] INSERM, UMR 942, Paris, France. [Januzzi, James L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Legrand, M (reprint author), Hop St Louis, AP HP, Hop Univ St Louis Lariboisiere, Dept Anesthesiol & Crit Care, F-75010 Paris, France. EM matthieu.m.legrand@gmail.com NR 18 TC 4 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 IS 10 BP 1824 EP 1828 DI 10.1007/s00134-013-3008-7 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 215TK UT WOS:000324233200017 PM 23828026 ER PT J AU Wamai, RG Ayissi, CA Oduwo, GO Perlman, S Welty, E Welty, T Manga, S Onyango, MA Ogembo, JG AF Wamai, Richard G. Ayissi, Claudine Akono Oduwo, Geofrey O. Perlman, Stacey Welty, Edith Welty, Thomas Manga, Simon Onyango, Monica A. Ogembo, Javier Gordon TI Awareness, knowledge and beliefs about HPV, cervical cancer and HPV vaccines among nurses in Cameroon: An exploratory study SO INTERNATIONAL JOURNAL OF NURSING STUDIES LA English DT Article DE Cervical cancer; Human papillomavirus virus; Knowledge and attitudes; Nurses; Vaccine; Cameroon ID SQUAMOUS INTRAEPITHELIAL LESIONS; HEALTH-CARE WORKERS; HUMAN-PAPILLOMAVIRUS; DEVELOPING-COUNTRIES; IMMUNIZATION PROGRAMS; VISUAL INSPECTION; WOMEN; VACCINATION; PREVENTION; ATTITUDES AB Background: While it is known that sub-Saharan African countries face multiple obstacles such as cost in adopting vaccination against human papillomavirus (HPV), the crucial role nurses can play in implementing such programs has not been adequately examined. Objectives: To investigate the knowledge and awareness of HPV, primary cause of cervical cancer and HPV vaccine among nurses working at four Cameroon Baptist Convention Health Services facilities, and to explore what factors influence nurses' willingness to inform and recommend HPV vaccine to adolescents and parents attending clinics. Design and setting: A structured questionnaire survey was administered to a convenience sample of nursing staff working at the four health facilities. Results: Of 192 eligible nurses 76(39.6%) participated in the study. There were moderately low levels of knowledge about HPV infection and prevention of cervical cancer, but a moderately high level of knowledge about HPV vaccine. Although 90.8% acknowledged that cervical cancer is directly linked to HPV infection, nearly 32% failed to identify it as a sexually transmitted infection (STI), while 43.4% believed it is an uncommon infection. Willingness to recommend the HPV vaccine was moderate, with 69.7% intentionally initiating discussions with patients about the subject. The most important factors considered when deciding to recommend the vaccine included effectiveness (56.6%) and side effects/safety (11.8%). Cost was less of a concern (6.6%), likely due to the availability of donated vaccine. Conclusion: Despite high awareness about HPV, more education about the virus, cervical cancer and the vaccine are required to further increase nurses' willingness to recommend the vaccine and strengthen strategies for reaching adolescents through nurses in Cameroon. Published by Elsevier Ltd. C1 [Wamai, Richard G.; Ayissi, Claudine Akono; Perlman, Stacey; Ogembo, Javier Gordon] Northeastern Univ, Boston, MA USA. [Ogembo, Javier Gordon] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Oduwo, Geofrey O.] KEMRI CDC Res & Publ Hlth Collaborat, Kisumu, Kenya. [Onyango, Monica A.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Ogembo, JG (reprint author), Harvard Univ, BIDMC, 3 Blackfan Circle Ctr Life Sci Bldg CLS,9th Floor, Boston, MA 02115 USA. EM jogembo@bidmc.harvard.edu OI Oduwo, Geofrey/0000-0003-2530-5428 NR 59 TC 13 Z9 13 U1 1 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7489 EI 1873-491X J9 INT J NURS STUD JI Int. J. Nurs. Stud. PD OCT PY 2013 VL 50 IS 10 BP 1399 EP 1406 DI 10.1016/j.ijnurstu.2012.12.020 PG 8 WC Nursing SC Nursing GA 218SA UT WOS:000324451600013 PM 23395482 ER PT J AU Zietman, AL AF Zietman, Anthony L. TI Falsification, Fabrication, and Plagiarism: The Unholy Trinity of Scientific Writing SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 [Zietman, Anthony L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Amer Soc Radiat Oncol, 8280 Willow Oaks Corp Dr,Suite 500, Fairfax, VA 22031 USA. EM redjournal@astro.org NR 4 TC 5 Z9 5 U1 0 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2013 VL 87 IS 2 BP 225 EP 227 DI 10.1016/j.ijrobp.2013.07.004 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 216UN UT WOS:000324310500001 PM 23958142 ER PT J AU Kim, KW Lee, JM Jeon, YS Lee, IJ Choi, Y Park, J Kiefer, B Kim, C Han, JK Choi, BI AF Kim, Kyung Won Lee, Jeong Min Jeon, Yong Sik Lee, In Joon Choi, YoonSeok Park, Jisuk Kiefer, Berthold Kim, Chin Han, Joon Koo Choi, Byung Ihn TI Vascular disrupting effect of CKD-516: preclinical study using DCE-MRI SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE CKD-516; Vascular disrupting agent; Tubulin; DCE-MRI ID TUBULIN POLYMERIZATION INHIBITOR; TUMOR VASCULATURE; ANTITUMOR-ACTIVITY; TARGETING AGENT; LIVER-TUMOR; PERFUSION; AVE8062; RABBIT AB Vascular disrupting agents (VDAs) are new class of anti-cancer drugs targeting pre-existing tumor vasculature which lead to tumor ischemia and necrosis. An innovative tubulin polymerization inhibitor, CKD-516, was recently developed as a VDA. We attempted to evaluate its tubulin destabilizing effect using immunofluorescence staining on human endothelial cells (HUVECs) and to ascertain its antivascular effect in a rabbit VX2 tumor model using dynamic contrast-enhanced (DCE) MRI by measuring the changes in kinetic parameters such as K-trans and IAUGC. Immunofluorescence staining using anti-tubulin and anti-actin antibodies on HUVECs showed that CKD-516 selectively disrupted tubulin component of the endothelial cytoskeleton. Serial DCE-MRI showed a significant decrease in K-trans and IAUGC parameters from baseline at 4 h (39.9 % in K-trans; -45.0 % in IAUGC) and at 24 h (-32.2 % in K-trans; -36.5 % in IAUGC), and a significant recovery at 48 h (22.9 % in K-trans; 34.8 % in IAUGC) following administration of CKD-516 at a 0.7-mg/kg dose. When the tumors were stratified according to the initial K-trans value of 0.1, tumors with a high K-trans > 0.1 which was indicative of having well-developed pre-existing vessels, showed greater reduction in K-trans and IAUGC values. On histologic examination, the degree of necrosis of treated tumors was significantly greater than that of untreated tumors. In summary, CKD-516 is an effective VDA which results in rapid vascular shutdown by targeting the tubulin component of tumor vessels and thus leads to necrosis. C1 [Kim, Kyung Won] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Jeong Min; Jeon, Yong Sik; Choi, YoonSeok; Park, Jisuk; Han, Joon Koo; Choi, Byung Ihn] Seoul Natl Univ Hosp, Dept Radiol, Seoul 110744, South Korea. [Lee, In Joon] Natl Canc Ctr, Ctr Liver Canc, Koyang, South Korea. [Kiefer, Berthold] Siemens Healthcare, Seoul, South Korea. [Kim, Chin] Chong Keun Dang Pharmaceut, Seoul, South Korea. [Lee, Jeong Min] Seoul Natl Univ, Coll Med, Dept Radiol, Seoul 110744, South Korea. [Lee, Jeong Min] Seoul Natl Univ, Coll Med, Inst Radiat Med, Seoul 110744, South Korea. RP Lee, JM (reprint author), Seoul Natl Univ, Coll Med, Dept Radiol, 28 Yeongon Dong, Seoul 110744, South Korea. EM jmsh@snu.ac.kr FU National Research Foundation of Korea (NRF); Korean Government [2011-0026127]; Ministry of Health, Welfare, and Family Affairs [A100895, A100265] FX This work was partially supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (2011-0026127) and by grants from the Korean Health and Medical Technology R&DProject, Ministry of Health, Welfare, and Family Affairs (A100895, A100265). We thank Bonnie Hami, M.A. (USA) for her editorial assistance. We also thank Hyunjun Ji and Peter Gall for his technical advice regarding Tissue 4D software. NR 23 TC 10 Z9 10 U1 0 U2 17 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD OCT PY 2013 VL 31 IS 5 BP 1097 EP 1106 DI 10.1007/s10637-012-9915-6 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 216HF UT WOS:000324272100001 PM 23299389 ER PT J AU Gupta, P Mulkey, F Hasserjian, RP Sanford, B Vij, R Hurd, DD Odenike, OM Bloomfield, CD Owzar, K Stone, RM Larson, RA AF Gupta, Pankaj Mulkey, Flora Hasserjian, Robert P. Sanford, Ben L. Vij, Ravi Hurd, David D. Odenike, Olatoyosi M. Bloomfield, Clara D. Owzar, Kouros Stone, Richard M. Larson, Richard A. CA Alliance Clinical Trials Oncology TI A phase II study of the oral VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK222584) in myelodysplastic syndrome: Cancer and Leukemia Group B study 10105 (Alliance) SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE (MeSH): Angiogenesis inhibitors; Humans; Myelodysplastic syndromes; Treatment outcome; Vascular endothelial growth factor ID ENDOTHELIAL GROWTH-FACTOR; ACUTE MYELOID-LEUKEMIA; METASTATIC COLORECTAL ADENOCARCINOMA; LIVER METASTASES; CELL GROWTH; FAS LIGAND; TUMOR; PTK787/ZK-222584; ANGIOGENESIS; EXPRESSION AB Background: Angiogenesis is implicated in the pathophysiology and progression of myelodysplastic syndromes (MDS). Vatalanib (PTK787/ZK222584; Novartis and Schering AG) inhibits receptor tyrosine kinases of vascular endothelial growth factor, platelet derived growth factor and c-Kit. We examined whether vatalanib induces hematological responses in MDS and/or delays progression to acute myeloid leukemia (AML) or death. Methods: Two cohorts were studied. Vatalanib 1250 mg orally was given once daily (cohort 1) or 750-1250 mg once daily in an intra-patient dose escalating schedule (cohort 2) in 28-day cycles to 155 patients with MDS; 142 patients were evaluable for response and 153 for toxicity. Results: The median age was 70.5 years; 51 % had low risk (International Prognostic Scoring System {IPSS} Low/Intermediate-1) and 32 % had high risk (IPSS Intermediate-2/High) MDS. Hematological improvement was achieved in 7/142 (5 %) patients; all 7 were among the 47 patients able to remain on vatalanib for at least 3 months (hematological improvement achieved in 15 % of these 47 patients). For patients with low risk and high risk MDS, respectively, median progression-free survivals were 15 and 6 months, median times to transformation to AML were 28 and 6 months, and median overall survivals were 36 and 10 months. The most frequent non-hematological adverse events grade a parts per thousand yen2 were fatigue, nausea or vomiting, dizziness, anorexia, ataxia, diarrhea, and pain. Two deaths (one intra-cerebral hemorrhage and one sudden death) were possibly related to vatalanib. Conclusions: Vatalanib induces improvement in blood counts in a small proportion of MDS patients. Clinical applicability is limited by side effects. C1 [Gupta, Pankaj] Univ Minnesota, Minneapolis, MN USA. [Mulkey, Flora; Sanford, Ben L.; Owzar, Kouros] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vij, Ravi] Washington Univ, St Louis, MO USA. [Hurd, David D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Odenike, Olatoyosi M.; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Bloomfield, Clara D.] Ohio State Univ, Columbus, OH 43210 USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gupta, Pankaj] Minneapolis VA Hlth Care Syst, Hematol Oncol Sect 111E, Minneapolis, MN 55417 USA. RP Gupta, P (reprint author), Minneapolis VA Hlth Care Syst, Hematol Oncol Sect 111E, 1 Vet Dr, Minneapolis, MN 55417 USA. EM gupta013@umn.edu OI Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute [CA16450, CA33601, CA32291, CA77440, CA03927, CA41287, CA77658, CA31946, CA101140]; Coleman Leukemia Research Foundation FX The research for CALGB 10105 (Alliance) was supported, in part, by National Cancer Institute grants no. CA16450 (PG), CA33601 (FM, BLS, KO), CA32291 (RPH, RMS), CA77440 (RV), CA03927 (DDH), CA41287 (OMO, RAL), CA77658 (CDB), CA31946 to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, M. D., Chair) and CA33601 to the Alliance Statistics and Data Center (Daniel J. Sargent, Ph.D.). Dr. Clara D. Bloomfield was supported in part by the National Cancer Institute (CA101140) and by the Coleman Leukemia Research Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 37 TC 8 Z9 10 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD OCT PY 2013 VL 31 IS 5 BP 1311 EP 1320 DI 10.1007/s10637-013-9978-z PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 216HF UT WOS:000324272100026 PM 23700288 ER PT J AU Brown, MC Mukerji, S Drottar, M Windsor, AM Lee, DJ AF Brown, M. Christian Mukerji, Sudeep Drottar, Marie Windsor, Alanna M. Lee, Daniel J. TI Identification of Inputs to Olivocochlear Neurons Using Transneuronal Labeling with Pseudorabies Virus (PRV) SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE superior olive; cochlear nucleus; inferior colliculus; reflex pathway; reticular formation ID POSTEROVENTRAL COCHLEAR NUCLEUS; SUPERIOR OLIVARY COMPLEX; NERVOUS-SYSTEM CIRCUITS; TENSOR TYMPANI MUSCLE; INFERIOR COLLICULUS; GUINEA-PIG; VESTIBULOCOCHLEAR ANASTOMOSIS; HORSERADISH-PEROXIDASE; MULTIPOLAR CELLS; FIBER POPULATION AB Olivocochlear (OC) neurons respond to sound and provide descending input that controls processing in the cochlea. The identities of neurons in the pathways providing inputs to OC neurons are incompletely understood. To explore these pathways, the retrograde transneuronal tracer pseudorabies virus (Bartha strain, expressing green fluorescent protein) was used to label OC neurons and their inputs in guinea pigs. Labeling of OC neurons began 1 day after injection into the cochlea. On day 2 (and for longer survival times), transneuronal labeling spread to the cochlear nucleus, inferior colliculus, and other brainstem areas. There was a correlation between the numbers of these transneuronally labeled neurons and the number of labeled medial (M) OC neurons, suggesting that the spread of labeling proceeds mainly via synapses on MOC neurons. In the cochlear nucleus, the transneuronally labeled neurons were multipolar cells including the subtype known as planar cells. In the central nucleus of the inferior colliculus, transneuronally labeled neurons were of two principal types: neurons with disc-shaped dendritic fields and neurons with dendrites in a stellate pattern. Transneuronal labeling was also observed in pyramidal cells in the auditory cortex and in centers not typically associated with the auditory pathway such as the pontine reticular formation, subcoerulean nucleus, and the pontine dorsal raphe. These data provide information on the identity of neurons providing input to OC neurons, which are located in auditory as well as non-auditory centers. C1 [Brown, M. Christian; Mukerji, Sudeep; Drottar, Marie; Windsor, Alanna M.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Brown, M. Christian; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Chris_Brown@meei.harvard.edu FU NIH [DCD 1 RO1 DC01089, DCD 1 K08 DC06285]; NIH Virus Center [P40RR018604] FX This study was supported by NIH grants DCD 1 RO1 DC01089 (to MCB) and DCD 1 K08 DC06285 (to DJL). We thank Dr. L. W. Enquist (Princeton University) for generously providing the PRV 152 (supported by an NIH Virus Center Grant P40RR018604), Dr. Thane E. Benson for helping with the micrographs, and Dr. M. Charles Liberman for comments on a previous version of the manuscript. Preliminary results of this study were presented in abstract form at the Association for Research in Otolaryngology Midwinter Meeting, February, 2010. NR 63 TC 7 Z9 7 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD OCT PY 2013 VL 14 IS 5 BP 703 EP 717 DI 10.1007/s10162-013-0400-5 PG 15 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 214EK UT WOS:000324113600008 PM 23728891 ER PT J AU Seligowski, AV Kaiser, APP Niles, BL Mori, DL King, LA King, DW AF Seligowski, Antonia V. Kaiser, Anica P. Pless Niles, Barbara L. Mori, DeAnna L. King, Lynda A. King, Daniel W. TI Sleep Quality as a Potential Mediator Between Psychological Distress and Diabetes Quality of Life in Veterans With Type 2 Diabetes SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE sleep quality; depression; anxiety; diabetes; quality of life ID COMORBID ANXIETY; PSYCHOMETRIC PROPERTIES; HEART HEALTH; OLDER-ADULTS; DEPRESSION; ASSOCIATION; SYMPTOMS; INVENTORY; DISTURBANCE; PREVALENCE AB Objective: The goal of this study was to explore sleep quality as a potential mediator between depression symptoms and diabetes quality of life (DQOL), and anxiety symptoms and DQOL. Method: Participants were 83 male and 3 female veterans with type 2 diabetes (M-age = 62.4). Self-report measures were completed during the baseline assessment of a larger intervention study conducted at the VA Boston Healthcare System. Results: Depression symptoms, anxiety symptoms, and sleep quality were all associated with DQOL. Additionally, sleep quality had a partial indirect effect on the relationships between depression symptoms and DQOL, and between anxiety symptoms and DQOL. Conclusions: These findings suggest that sleep quality may have an important role in the way that psychological distress affects diabetes quality of life. (C) 2012 Wiley Periodicals, Inc. C1 [Seligowski, Antonia V.; Kaiser, Anica P. Pless; Niles, Barbara L.; Mori, DeAnna L.; King, Lynda A.; King, Daniel W.] VA Boston Healthcare Syst, Boston, MA USA. [Kaiser, Anica P. Pless; Niles, Barbara L.; Mori, DeAnna L.; King, Lynda A.; King, Daniel W.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Seligowski, AV (reprint author), 150 South Huntington Ave 116B-2, Boston, MA 02130 USA. EM avic858@gmail.com NR 50 TC 4 Z9 6 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD OCT PY 2013 VL 69 IS 10 BP 1121 EP 1131 DI 10.1002/jclp.21866 PG 11 WC Psychology, Clinical SC Psychology GA 213CU UT WOS:000324032200010 PM 22638910 ER PT J AU Cases, M Furlong, LI Albanell, J Altman, RB Bellazzi, R Boyer, S Brand, A Brookes, AJ Brunak, S Clark, TW Gea, J Ghazal, P Graf, N Guigo, R Klein, TE Lopez-Bigas, N Maojo, V Mons, B Musen, M Oliveira, JL Rowe, A Ruch, P Shabo, A Shortliffe, EH Valencia, A van der Lei, J Mayer, MA Sanz, F AF Cases, M. Furlong, L. I. Albanell, J. Altman, R. B. Bellazzi, R. Boyer, S. Brand, A. Brookes, A. J. Brunak, S. Clark, T. W. Gea, J. Ghazal, P. Graf, N. Guigo, R. Klein, T. E. Lopez-Bigas, N. Maojo, V. Mons, B. Musen, M. Oliveira, J. L. Rowe, A. Ruch, P. Shabo, A. Shortliffe, E. H. Valencia, A. van der Lei, J. Mayer, M. A. Sanz, F. TI Improving data and knowledge management to better integrate health care and research SO JOURNAL OF INTERNAL MEDICINE LA English DT Editorial Material ID TRANSLATIONAL RESEARCH; DRUG-INTERACTIONS; SEMANTIC-WEB; MEDICINE; FRAMEWORK C1 [Cases, M.; Furlong, L. I.; Lopez-Bigas, N.; Mayer, M. A.; Sanz, F.] Univ Pompeu Fabra, DCEXS, IMIM, Res Programme Biomed Informat GRIB, Barcelona, Spain. [Albanell, J.] Univ Pompeu Fabra, DCEXS, IMIM, Hosp del Mar,Serv Oncol, Barcelona, Spain. [Altman, R. B.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Altman, R. B.; Klein, T. E.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Altman, R. B.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Bellazzi, R.] Univ Pavia, Dipartimento Ingn Ind & Informaz, I-27100 Pavia, Italy. [Boyer, S.] AstraZeneca, Safety Assessment, Molndal, Sweden. [Brand, A.] Maastricht Univ, Inst Publ Hlth Genom, Maastricht, Netherlands. [Brookes, A. J.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Brunak, S.] Tech Univ Denmark, Univ Copenhagen, Ctr Biol Sequence Anal, Ctr Prot Res, DK-2800 Lyngby, Denmark. [Clark, T. W.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Cambridge, MA USA. [Gea, J.] Univ Pompeu Fabra, CIBERES, DCEXS, IMIM,Hosp del Mar,Serv Pneumol, Barcelona, Spain. [Ghazal, P.] Univ Edinburgh, Div Pathway Med, Edinburgh, Midlothian, Scotland. [Graf, N.] Univ Saarland, Dept Pediat Oncol & Hematol, Homburg, Germany. [Guigo, R.] CRG, Barcelona, Spain. [Guigo, R.; Valencia, A.; Sanz, F.] Spanish Inst Bioinformat INB, Madrid, Spain. [Lopez-Bigas, N.] ICREA, Barcelona, Spain. [Maojo, V.] Univ Politecn Madrid, Biomed Informat Grp, Madrid, Spain. [Mons, B.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Mons, B.] Netherlands Bioinformat Ctr, Nijmegen, Netherlands. [Musen, M.] Stanford Univ, Stanford Ctr Biomed Informat Res, Stanford, CA 94305 USA. [Oliveira, J. L.] Univ Aveiro, DETI IEETA, P-3800 Aveiro, Portugal. [Ruch, P.] Univ Appl Sci, BITEM, Geneva, Switzerland. [Shabo, A.] IBM Res Lab, Haifa, Israel. [Shortliffe, E. H.] Arizona State Univ, Phoenix, AZ USA. [Shortliffe, E. H.] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Valencia, A.] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain. [van der Lei, J.] Erasmus Univ, Dept Med Informat, Med Ctr, NL-3000 DR Rotterdam, Netherlands. RP Sanz, F (reprint author), C Dr Aiguader 88, Barcelona 08003, Spain. EM ferran.sanz@upf.edu RI Oliveira, Jose Luis/A-2223-2012; Sanz, Ferran/B-3852-2009; Gea, Joaquim/E-4841-2014; Mayer, Miguel Angel/K-5255-2014; Guigo, Roderic/D-1303-2010; Lopez-Bigas, Nuria/F-6193-2011; Valencia, Alfonso/I-3127-2015; CESAM, UA/M-3762-2015; Gasull, Martina/A-6630-2013; OI Oliveira, Jose Luis/0000-0002-6672-6176; Rowe, Anthony/0000-0003-1829-1179; Sanz, Ferran/0000-0002-7534-7661; Gea, Joaquim/0000-0001-8718-7346; Mayer, Miguel Angel/0000-0003-0362-6298; Guigo, Roderic/0000-0002-5738-4477; Lopez-Bigas, Nuria/0000-0003-4925-8988; Furlong, Laura I./0000-0002-9383-528X; Mons, Barend/0000-0003-3934-0072; Valencia, Alfonso/0000-0002-8937-6789; Ruch, Patrick/0000-0002-3374-2962 FU NHGRI NIH HHS [U54 HG004028]; NIGMS NIH HHS [R24 GM061374] NR 22 TC 15 Z9 15 U1 1 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD OCT PY 2013 VL 274 IS 4 BP 321 EP 328 DI 10.1111/joim.12105 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 213OZ UT WOS:000324068800003 PM 23808970 ER PT J AU Gurkan, S Cabinian, A Lopez, V Bhaumik, M Chang, JM Rabson, AB Mundel, P AF Gurkan, Sevgi Cabinian, Allison Lopez, Victoria Bhaumik, Mantu Chang, Jer-Ming Rabson, Arnold B. Mundel, Peter TI Inhibition of type I interferon signalling prevents TLR ligand-mediated proteinuria SO JOURNAL OF PATHOLOGY LA English DT Article DE podocyte; TLR; proteinuria; type I IFN ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; TOLL-LIKE RECEPTORS; NEPHROTIC-SYNDROME; AUTOIMMUNE-DISEASES; ACTIN CYTOSKELETON; KIDNEY PODOCYTES; ALPHA; CELLS; EXPRESSION; PATHWAYS AB The mechanisms by which inflammation or autoimmunity causes proteinuric kidney disease remain elusive. Yet proteinuria is a hallmark and a prognostic indicator of kidney disease, and also an independent risk factor for cardiovascular morbidity and mortality. Podocytes are an integral component of the kidney filtration barrier and podocyte injury leads to proteinuria. Here we show that podocytes, which receive signals from the vascular space including circulating antigens, constitutively express TLR1-6 and TLR8. We find that podocytes can respond to TLR ligands including staphylococcal enterotoxin B (SEB), poly I:C, or lipopolysaccharide (LPS) with pro-inflammatory cytokine release and activation of type I interferon (IFN) signalling. This in turn stimulates podocyte B7-1 expression and actin remodelling in vitro and transient proteinuria in vivo. Importantly, the treatment of mice with a type I IFN receptor-blocking antibody (Ab) prevents LPS-induced proteinuria. These results significantly extend our understanding of podocyte response to immune stimuli and reveal a novel mechanism for infection- or inflammation-induced transient proteinuria. Dysregulation or aberrant activation of this response may result in persistent proteinuria and progressive glomerular disease. In summary, the inhibition of glomerular type I IFN signalling with anti-IFN Abs may be a novel therapy for proteinuric kidney diseases. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Gurkan, Sevgi; Cabinian, Allison; Lopez, Victoria; Bhaumik, Mantu; Rabson, Arnold B.] Rutgers State Univ, Dept Pediat, Child Hlth Inst New Jersey, New Brunswick, NJ 08903 USA. [Chang, Jer-Ming] Kaohsiung Med Univ, Dept Internal Med, Kaohsiung, Taiwan. [Mundel, Peter] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Mundel, Peter] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02129 USA. RP Gurkan, S (reprint author), Rutgers Robert Wood Johnson Med Sch, Dept Pediat, 89 French St, New Brunswick, NJ 08901 USA. EM gurkanse@rwjms.rutgers.edu; mundel.peter@mgh.harvard.edu FU NIH [DK57683, DK062472, DK093682-01]; Robert Wood Foundation (RWJF) [67038] FX We would like to thank Amale Laquar, HsinChing Lin, and Celine Granier for technical assistance. We also thank Anna Greka, Boston, for helpful discussion. This work was supported by NIH grants DK57683, DK062472, and DK093682-01 (to PM) and a Robert Wood Foundation grant to the Child Health Institute of New Jersey (RWJF grant No 67038; to SG). NR 45 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 2013 VL 231 IS 2 BP 248 EP 256 DI 10.1002/path.4235 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 213XC UT WOS:000324092800011 PM 24151637 ER PT J AU Barbieri, CE Sboner, A Rubin, MA Garraway, LA AF Barbieri, Christopher E. Sboner, Andrea Rubin, Mark A. Garraway, Levi A. TI Re: Stoehr et al. Lack of evidence for frequent MED12 p.L1224F mutation in prostate tumours from Caucasian patients. J Pathol 2013; 230: 453-456 SO JOURNAL OF PATHOLOGY LA English DT Letter C1 [Barbieri, Christopher E.; Rubin, Mark A.] Weill Cornell Med Coll, Dept Urol, New York, NY 10065 USA. [Barbieri, Christopher E.; Sboner, Andrea; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Sboner, Andrea] Weill Cornell Med Coll, Dept Physiol & Biophys, Inst Computat Biomed, New York, NY 10065 USA. [Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [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. RP Barbieri, CE (reprint author), Weill Cornell Med Coll, Dept Urol, New York, NY 10065 USA. RI Sboner, Andrea/C-6487-2008; OI Sboner, Andrea/0000-0001-6915-3070; Barbieri, Christopher/0000-0002-0381-1947; Rubin, Mark/0000-0002-8321-9950 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 2013 VL 231 IS 2 BP 271 EP 271 DI 10.1002/path.4216 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 213XC UT WOS:000324092800013 PM 23729306 ER PT J AU Stange, JP Sylvia, LG Magalhaes, PVD Frank, E Otto, MW Miklowitz, DJ Berk, M Nierenberg, AA Deckersbach, T AF Stange, Jonathan P. Sylvia, Louisa G. da Silva Magalhaes, Pedro Vieira Frank, Ellen Otto, Michael W. Miklowitz, David J. Berk, Michael Nierenberg, Andrew A. Deckersbach, Thilo TI Extreme attributions predict transition from depression to mania or hypomania in bipolar disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Attributional style; Cognitive style; Cognitive vulnerability; Mania; Hypomania; Manic switch ID BEHAVIORAL-APPROACH SYSTEM; TREATMENT ENHANCEMENT PROGRAM; LIFE EVENTS; SPECTRUM DISORDERS; COGNITIVE THERAPY; INTERNAL STATES; MOOD DISORDERS; STEP-BD; ANXIETY DISORDERS; SOCIAL COGNITION AB Background: Relatively little is known about psychological predictors of the onset of mania among individuals with bipolar disorder, particularly during episodes of depression. In the present study we investigated attributional style as a predictor of onset of hypomanic, manic or mixed episodes among bipolar adults receiving psychosocial treatment for depression. We hypothesized that "extreme" (i.e., excessively pessimistic or optimistic) attributions would predict a greater likelihood of developing an episode of mood elevation. Method: Outpatients with DSM-IV bipolar I or II disorder (N = 105) enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomly allocated to one of three types of intensive psychotherapy for depression or a brief psychoeducational intervention. Patients completed a measure of attributional style at baseline and were followed prospectively for up to one year. All analyses were by intent to treat. Results: Logistic regressions and Cox proportional hazards models indicated that extreme (both positively-and negatively-valenced) attributions predicted a higher likelihood of (and shorter time until) transition from depression to a (hypo)manic or mixed episode (ps < .04), independent of the effects of manic or depressive symptom severity at baseline. Extreme attributions were also retrospectively associated with more lifetime episodes of (hypo)mania and depression (ps < .05). Conclusions: Evaluating extreme attributions may help clinicians to identify patients who are at risk for experiencing a more severe course of bipolar illness, and who may benefit from treatments that introduce greater cognitive flexibility. (C) 2013 Elsevier Ltd. All rights reserved. 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, BR-90046900 Porto Alegre, RS, Brazil. [Frank, Ellen] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Miklowitz, David J.] Univ Calif Los Angeles, Sch Med, Div Child & Adolescent Psychiat, Los Angeles, CA USA. [Berk, Michael] Deakin Univ, Sch Med, Geelong, Vic 3217, Australia. [Berk, Michael] Univ Melbourne, Orygen Youth Hlth Res Ctr, Ctr Youth Mental Hlth, Florey Inst Neurosci & 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 Floor, Boston, MA 02114 USA. EM tdeckersbach@partners.org RI Berk, Michael/M-7891-2013; Magalhaes, Pedro/A-8519-2008; OI Berk, Michael/0000-0002-5554-6946; Magalhaes, Pedro/0000-0002-5644-6357; Miklowitz, David/0000-0002-9647-6147 FU National Institute of Mental Health [N01MH80001, MH29618, MH43931, MH55101]; National Research Service Award from NIMH [F31MH099761]; NIMH; New Harbinger Publishers; Guilford Press; American Psychological Association Press; Brain and Behavior Research Foundation; Danny Alberts Foundation; Attias Family Foundation; John Wiley and Sons; NIH; NHMRC; CRC; Rotary; Simons Foundation; Allen Unwin; Cambridge University Press; K-23 NIMH Career Award [1K23MH074895-01A2]; NARSAD; TSA; OCF; Tufts University; MGH Psychiatry Academy; Brain Cells 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; NIDA; Oxford University Press; NIA; AHRQ; Janssen Pharmaceuticals; Forest Research Institute; Shire Development Inc.; Medtronic; Cyberonics; Northstar FX STEP-BD was funded in part by contract N01MH80001 from the National Institute of Mental Health (Gary Sachs). Support for the development of the psychosocial treatments was provided by grants MH29618 (Ellen Frank), MH43931 (David Miklowitz), and MH55101 (David Miklowitz) from the National Institute of Mental Health and by the National Alliance for Research on Schizophrenia and Depression (David Miklowitz). Jonathan Stange was supported by National Research Service Award F31MH099761 from NIMH. Louisa Sylvia was employed by Massachusetts General Hospital, served as a Consultant for Bracket Global and Clintara, received research support from NIMH, is a former stockholder in Concordant Rater Systems, and has received support from New Harbinger Publishers. Pedro Vieira da Silva Magalhaes reports no relevant financial interests. Ellen Frank has served as a consultant for Servier International, and has received other financial or material support from Guilford Press and the American Psychological Association Press. Michael Otto has served as a consultant for Micro-Transponder, Inc. David Miklowitz has received research support or honoraria from NIMH, Brain and Behavior Research Foundation, Danny Alberts Foundation, and Attias Family Foundation; He has received other financial or material support from Guilford Press, and John Wiley and Sons. Michael Berk is an employee of Barwon Health, Deakin University; he has received research support from NIH; NHMRC, CRC, Rotary and the Simons Foundation; he has received honoraria from Lundbeck, Astrazeneca, Servier, Lilly, and ISBD Korea; he has served as a speaker or on the advisory board for Astrazeneca, Lundbeck, Lilly, and Janssen; and he has received financial or material support from Allen & Unwin and Cambridge University Press. Andrew 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 Pharma, L.P./Mylan Inc., Israel Society for Biological Psychiatry, John Hopkins University, National Association of Continuing Education, PAL Pamlabs, Physicians Postgraduate Press, Ridge Diagnostics, Slack Publishing, Sunovion, Teva Pharmaceuticals, University of Florida, University of Michigan, University of New Mexico, University of Miami, University of Wisconsin, Wolters Klower Publishing. Potential consulting honoraria from Astra Zeneca, Bristol Myers Squibb, Forest, Pfizer, Ridge Diagnostics. Potential support of research at MGH through Biogen Idec, Dey Pharmaceuticals, Pamlabs, Shire, and Sunovian. He owns stock options in Appliance Computing, Inc. (MindSite.com) and BrainCells, 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 Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). Thilo Deckersbach was supported in part by a K-23 NIMH Career Award 1K23MH074895-01A2. His research has also been funded by NARSAD, TSA, OCF and Tufts University. He has received honoraria, consultation fees and/or royalties from the MGH Psychiatry Academy, Brain Cells Inc.; , Systems Research and Applications Corporation, Boston University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, Tufts University, NIDA and Oxford University Press. He has also participated in research funded by NIH, NIA, AHRQ, Janssen Pharmaceuticals, The Forest Research Institute, Shire Development Inc., Medtronic, Cyberonics, and Northstar. NR 62 TC 4 Z9 4 U1 2 U2 30 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 OCT PY 2013 VL 47 IS 10 BP 1329 EP 1336 DI 10.1016/j.jpsychires.2013.05.016 PG 8 WC Psychiatry SC Psychiatry GA 212TC UT WOS:000324004700007 PM 23791456 ER PT J AU Zhang, XY Al Jurdi, RK Zoghbi, AW Chen, DC Xiu, MH Tan, YL Yang, FD Kosten, TR AF Zhang, Xiang Yang Al Jurdi, Rayan K. Zoghbi, Anthony William Chen, Da Chun Xiu, Mei Hong Tan, Yun Long Yang, Fu De Kosten, Thomas R. TI Prevalence, demographic and clinical correlates of suicide attempts in Chinese medicated chronic inpatients with schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Suicide; Risk factors; Smoking; China ID RANDOMIZED CONTROLLED-TRIAL; NEGATIVE SYNDROME SCALE; 1ST EPISODE PSYCHOSIS; QUALITY-OF-LIFE; CIGARETTE-SMOKING; RISK-FACTORS; 1ST-EPISODE PSYCHOSIS; REVISED NOMENCLATURE; PSYCHIATRIC-PATIENTS; SPECTRUM DISORDERS AB The high prevalence of suicide in schizophrenia may be related to its demographic and clinical characteristics. Because suicide prevalence and its associations with clinical variables are less well characterized in Chinese than European patients with schizophrenia, we assessed the suicide attempts in 520 Chinese inpatients with schizophrenia. The suicide attempt data were collected from medical case notes and interviews with the patients and their family members. Patients were rated on the Positive and Negative Syndrome Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS). Smoking severity was evaluated using clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND). We found a suicide attempt rate of 9.2% in these schizophrenic inpatients. The attempters were single, had a significantly younger age but more hospitalizations, had higher depressive symptoms, and began smoking at an earlier age, smoked more cigarettes each day and had higher FTND total scores than patients without suicide attempts. The logistic regression analysis also indicated that suicide attempts were associated with the number of hospitalizations, depressive symptoms and FTND total scores. These results suggest that Chinese inpatients with schizophrenia attempt suicide more often than the general population. Further, some demographic and clinical variables are risk factors for suicide attempts in schizophrenia. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Zhang, Xiang Yang; Al Jurdi, Rayan K.; Zoghbi, Anthony William; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Al Jurdi, Rayan K.; Zoghbi, Anthony William; Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; Tan, Yun Long; Yang, Fu De; Kosten, Thomas R.] Peking Univ, Beijing HuiLongGuan Hosp, Beijing 100871, Peoples R China. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was supported by the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. These sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 54 TC 6 Z9 7 U1 2 U2 11 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 OCT PY 2013 VL 47 IS 10 BP 1370 EP 1375 DI 10.1016/j.jpsychires.2013.05.024 PG 6 WC Psychiatry SC Psychiatry GA 212TC UT WOS:000324004700013 PM 23791457 ER PT J AU Smits, JAJ Rosenfield, D Otto, MW Marques, L Davis, ML Meuret, AE Simon, NM Pollack, MH Hofmann, SG AF Smits, Jasper A. J. Rosenfield, David Otto, Michael W. Marques, Luana Davis, Michelle L. Meuret, Alicia E. Simon, Naomi M. Pollack, Mark H. Hofmann, Stefan G. TI D-cycloserine enhancement of exposure therapy for social anxiety disorder depends on the success of exposure sessions SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE CBT; Cognitive behavioral therapy; Exposure therapy; Fear extinction; D-cycloserine; Moderators; Social anxiety disorder; Social phobia ID COGNITIVE-BEHAVIORAL THERAPY; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; EXTINCTION; FEAR; AUGMENTATION; REDUCTION; REAPPRAISAL; EFFICACY AB Objective: The evidence for the efficacy of D-cycloserine (DCS) for augmenting cognitive behavioral therapy (CBT) for anxiety disorders has been mixed. Guided by preclinical research and initial findings from a small-scale study involving humans, we tested the hypothesis that DCS enhancement of exposure therapy would be specific to successful exposure sessions. Method: Medication-free adults with generalized social anxiety disorder (N = 145) received 50 mg of DCS or placebo 1 h before each of 5 exposure sessions that were part of a standardized 12-session group CBT protocol. Participants provided fear ratings at the beginning and just before the end of exposure exercises. Independent raters, blind to group assignment, administered the clinical global impression improvement and severity scales at each session and at posttreatment. Results: Mixed-effects analyses revealed that, among patients who reported low fear at the end of an exposure session, those who had received DCS evidenced significantly greater clinical improvement at the next session, relative to those who had received placebo. In contrast, when exposure end fear was high, patients receiving DCS exhibited less clinical improvement at the following session than patients receiving placebo. Similarly, patients who had received DCS evidenced lower clinical severity at posttreatment, relative to patients who had received placebo, only when their average end fear for medication-augmented sessions had been in the low to moderate range. Finally, these moderating effects of exposure success as indexed by end fear were not better accounted for by within-session extinction. Conclusions: The efficacy of DCS for augmenting exposure-based CBT depends on the success of exposure sessions. These findings may help guide the development of an algorithm for the effective use of DCS for augmenting exposure-based CBT. Trial registry: http://www.ClinicalTrials.gov, ID# NCT00633984, http://www.clinicaltrials.gov/ct2/show/NCT00633984. (C)2013 Elsevier Ltd. All rights reserved. C1 [Smits, Jasper A. J.; Rosenfield, David; Davis, Michelle L.] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. [Otto, Michael W.; Meuret, Alicia E.; Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02214 USA. [Marques, Luana; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pollack, Mark H.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Fl, Boston, MA 02214 USA. EM jsmits@smu.edu; shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014; Smits, Jasper/A-4350-2008; OI Hofmann, Stefan/0000-0002-3548-9681; Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693 FU NIH from the National Institute of Mental Health [R01MH078308, R01MH075889] FX This study was funded by NIH grants R01MH078308 and R01MH075889 from the National Institute of Mental Health. The sponsor (NIH) had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. Drs. Smits, Pollack, and Hofmann had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 41 TC 34 Z9 34 U1 3 U2 22 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 OCT PY 2013 VL 47 IS 10 BP 1455 EP 1461 DI 10.1016/j.jpsychires.2013.06.020 PG 7 WC Psychiatry SC Psychiatry GA 212TC UT WOS:000324004700025 PM 23870811 ER PT J AU Kasotakis, G Duggan, M Li, YQ O'Dowd, D Baldwin, K de Moya, MA King, DR Alam, HB Velmahos, G AF Kasotakis, George Duggan, Michael Li, Yongqing O'Dowd, David Baldwin, Keith de Moya, Marc A. King, David R. Alam, Hasan B. Velmahos, George TI Optimal pressure of abdominal gas insufflation for bleeding control in a severe swine splenic injury model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Hemorrhage control; Abdominal insufflation; Pneumoperitoneum; Pre-hospital; Resuscitation; Fluidless; Bleeding; Trauma; Abdominal; Injury ID DECREASES BLOOD-LOSS; RESUSCITATION; PNEUMOPERITONEUM; HEMORRHAGE; MORTALITY; SYSTEMS AB Background: We previously demonstrated that abdominal gas insufflation (AGI) reduces intra-abdominal bleeding. To date, this is the only method that holds promise for reducing mortality from internal bleeding in a pre-hospital setting. We aimed to assess the optimal AGI pressure and the effectiveness of a portable miniaturized insufflator in abdominal bleeding control. Materials and methods: We randomized 15 Yorkshire swine to receive AGI of 20, 25 or 30 mm Hg after sustaining a standardized severe splenic injury, to determine the ideal pressure for optimal bleeding control. We randomized six (40%) to insufflation with a custom-designed, battery-operated, 7-oz portable CO2 tank, whereas we used a standard laparoscopic insufflator for the remainder. Intravenous fluid boluses were administered as needed to maintain a mean arterial pressure of >60 mm Hg. At 30 min, the animals were re-laparotomized and their hemoperitoneum was quantified. Results: Target peritoneal pressures were achieved and maintained successfully with both insufflation methods. There was a trend toward greater blood loss and fluid requirements in the 30-mmHg group (P = 0.71 and 0.97, respectively). Increasing the AGI led to less predictable blood loss and fluid resuscitation requirements, as well as worsening of tissue perfusion markers (pH and lactate), likely because of iatrogenic abdominal compartment syndrome. Conclusions: All target peritoneal pressures were easily and reliably achieved with the portable CO2 insufflator. Abdominal gas insufflation produced optimal bleeding control at 20 mm Hg. This technology could be used in a pre-hospital setting to control otherwise lethal hemorrhage at pressures typically used for standard laparoscopic surgery and proven to be safe. Published by Elsevier Inc. C1 [Kasotakis, George; Duggan, Michael; Li, Yongqing; de Moya, Marc A.; King, David R.; Alam, Hasan B.; Velmahos, George] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02118 USA. [O'Dowd, David; Baldwin, Keith] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. RP Kasotakis, G (reprint author), Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp,Dept Surg, 677 Huntington Ave,Mailbox 620, Boston, MA 02118 USA. EM gkasotakis@mail.harvard.edu OI King, David/0000-0003-1028-1478; Kasotakis, George/0000-0002-7630-0742 NR 28 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2013 VL 184 IS 2 BP 931 EP 936 DI 10.1016/j.jss.2013.03.016 PG 6 WC Surgery SC Surgery GA 215XE UT WOS:000324243500039 PM 23545409 ER PT J AU Corcorran, MA Olson, JM Hecht, C Knezevich, S Vary, JC AF Corcorran, Maria A. Olson, Jonathan M. Hecht, Corinne Knezevich, Stevan Vary, Jay C. TI Eruptive squamous cell carcinoma in a patient receiving abatacept for rheumatoid arthritis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Corcorran, Maria A.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Olson, Jonathan M.; Hecht, Corinne; Vary, Jay C.] Univ Washington, Dept Med, Div Dermatol, Seattle, WA 98195 USA. [Knezevich, Stevan] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Olson, Jonathan M.; Hecht, Corinne; Knezevich, Stevan; Vary, Jay C.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Vary, JC (reprint author), Univ Washington, Sch Med, Div Dermatol, Dept Med, 1959 NE Pacific St,Rm BB 1353,Box 356524, Seattle, WA 98195 USA. EM jvary@uw.edu NR 5 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2013 VL 69 IS 4 BP E178 EP E179 DI 10.1016/j.jaad.2013.04.018 PG 3 WC Dermatology SC Dermatology GA 215VM UT WOS:000324238900009 PM 24034388 ER PT J AU Goswami, D Devarakonda, S Chalmers, MJ Pascal, BD Spiegelman, BM Griffin, PR AF Goswami, Devrishi Devarakonda, Srikripa Chalmers, Michael J. Pascal, Bruce D. Spiegelman, Bruce M. Griffin, Patrick R. TI Time Window Expansion for HDX Analysis of an Intrinsically Disordered Protein SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE Hydrogen deuterium exchange; Automation; Electrospray ionization; HPLC; Mass spectrometry; Nuclear receptors; Intrinsically disordered proteins; Conformational mobility; Protein dynamics ID EXCHANGE MASS-SPECTROMETRY; HYDROGEN-EXCHANGE; UNSTRUCTURED PROTEINS; LIGAND INTERACTIONS; NUCLEAR RECEPTORS; STRUCTURAL BASIS; BINDING; DYNAMICS; DISEASES; GAMMA AB Application of typical HDX methods to examine intrinsically disordered proteins (IDP), proteins that are natively unstructured and highly dynamic at physiological pH, is limited because of the rapid exchange of unprotected amide hydrogens with solvent. The exchange rates of these fast exchanging amides are usually faster than the shortest time scale (10 s) employed in typical automated HDX-MS experiments. Considering the functional importance of IDPs and their association with many diseases, it is valuable to develop methods that allow the study of solution dynamics of these proteins as well as the ability to probe the interaction of IDPs with their wide range of binding partners. Here, we report the application of time window expansion to the millisecond range by altering the on-exchange pH of the HDX experiment to study a well-characterized IDP; the activation domain of the nuclear receptor coactivator, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). This method enabled mapping the regions of PGC-1 alpha that are stabilized upon binding the ligand binding domain (LBD) of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma). We further demonstrate the method's applicability to other binding partners of the IDP PGC-1 alpha and pave the way for characterizing many other biologically important ID proteins. C1 [Goswami, Devrishi; Chalmers, Michael J.; Pascal, Bruce D.; Griffin, Patrick R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA. [Devarakonda, Srikripa; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Devarakonda, Srikripa; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Griffin, PR (reprint author), Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA. EM pgriffin@scripps.edu RI Goswami, Devrishi/A-8891-2014 FU Pfizer postdoctoral fellowship; NIGMS [GM084041] FX The authors are grateful for support from Ruben Garcia-Ordonez for the protein preparation. The work was supported in part by a Pfizer postdoctoral fellowship and NIGMS (GM084041, to P.R.G.). NR 45 TC 21 Z9 21 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD OCT PY 2013 VL 24 IS 10 BP 1584 EP 1592 DI 10.1007/s13361-013-0669-y PG 9 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 215TV UT WOS:000324234300015 PM 23884631 ER PT J AU Nazer, B Ray, KK Murphy, SA Gibson, CM Cannon, CP AF Nazer, Babak Ray, Kausik K. Murphy, Sabina A. Gibson, C. Michael Cannon, Christopher P. TI Urinary albumin concentration and long-term cardiovascular risk in acute coronary syndrome patients: a PROVE IT-TIMI 22 substudy SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Albuminuria; Microalbuminuria; Acute coronary syndromes; Myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; PROGNOSTIC-SIGNIFICANCE; GENERAL-POPULATION; EARLY MORTALITY; ALL-CAUSE; MICROALBUMINURIA; EXCRETION; INDIVIDUALS; HEALTH; DEATH AB Albuminuria has been shown to be associated with mortality and cardiovascular events, independent of traditional cardiovascular risk factors. This suggests that albuminuria may not just represent glomerular damage, but may be a marker of more diffuse endothelial dysfunction. We investigated the relationship between urinary albumin levels after an acute coronary syndrome and cardiovascular outcomes in statin treated subjects after acute coronary syndromes (ACS). Furthermore we assessed the effect of intensive statin treatment on albuminuria among patients in the PROVE IT-TIMI 22 trial, in which patients who had been hospitalized with ACS were randomized to pravastatin 40 mg (standard therapy) or atorvastatin 80 mg daily (intensive therapy). In univariate analyses, increasing urine albumin concentration was associated with increased risk of myocardial infarction, stroke, heart failure, and composite of death, myocardial infarction and stroke at 2 years. However, in a multivariable model containing traditional cardiovascular risk factors, albuminuria was not an independent predictor of the primary PROVE IT endpoint of death, myocardial infarction, unstable angina, revascularization and stroke, and was only an independent predictor of all-cause mortality at urinary albumin concentration > 300 mcg/ml. There was no significant change in urinary albumin concentration from enrolment to end of study in either the standard or intensive statin therapy groups, and no significant difference between treatment groups. Our results suggest that after an acute coronary syndrome in statin treated patients, microalbuminuria may reflect traditional cardiovascular risk factor burden and offer little prognostic information independent of those factors. C1 [Nazer, Babak] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Ray, Kausik K.] St Georges Univ London, Div Cardiac & Vasc Sci, London, England. [Murphy, Sabina A.; Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Murphy, Sabina A.; Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Gibson, C. Michael] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc, Boston, MA 02215 USA. RP Ray, KK (reprint author), St Georges Univ London, Div Cardiac & Vasc Sci, London, England. EM kray@sgul.ac.uk FU Bristol-Myers Squibb; Sankyo FX PROVE IT-TIMI 22 was funded by Bristol-Myers Squibb and Sankyo. NR 21 TC 6 Z9 7 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2013 VL 36 IS 3 BP 233 EP 239 DI 10.1007/s11239-012-0853-0 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 217BL UT WOS:000324331400002 PM 23212806 ER PT J AU Denard, J Marolleau, B Jenny, C Rao, TN Fehling, HJ Voit, T Svinartchouk, F AF Denard, Jerome Marolleau, Beatrice Jenny, Christine Rao, Tata Nageswara Fehling, Hans Joerg Voit, Thomas Svinartchouk, Fedor TI C-Reactive Protein (CRP) Is Essential for Efficient Systemic Transduction of Recombinant Adeno-Associated Virus Vector 1 (rAAV-1) and rAAV-6 in Mice SO JOURNAL OF VIROLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; FC-GAMMA-RI; ENDOTHELIAL-CELLS; HEPARIN-BINDING; GENE-EXPRESSION; TISSUE TROPISM; MUSCLE; SEROTYPES; TYPE-1; SPECIFICITY AB The clinical relevance of gene therapy using the recombinant adeno-associated virus (rAAV) vectors often requires widespread distribution of the vector, and in this case, systemic delivery is the optimal route of administration. Humoral blood factors, such as antibodies or complement, are the first barriers met by the vectors administered systemically. We have found that other blood proteins, galectin 3 binding protein (G3BP) and C-reactive protein (CRP), can interact with different AAV serotypes in a species-specific manner. While interactions of rAAV vectors with G3BP, antibodies, or complement lead to a decrease in vector efficacy, systemic transduction of the CRP-deficient mouse and its respective control clearly established that binding to mouse CRP (mCRP) boosts rAAV vector 1 (rAAV-1) and rAAV-6 transduction efficiency in skeletal muscles over 10 times. Notably, the high efficacy of rAAV-6 in CRP-deficient mice can be restored by reconstitution of the CRP-deficient mouse with mCRP. Human CRP (hCRP) does not interact with either rAAV-1 or rAAV-6, and, consequently, the high efficiency of mCRP-mediated muscle transduction by these serotypes in mice cannot be translated to humans. No interaction of mCRP or hCRP was observed with rAAV-8 and rAAV-9. We show, for the first time, that serum components can significantly enhance rAAV-mediated tissue transduction in a serotype-and species-specific manner. Bioprocessing in body fluids should be considered when transfer of a preclinical proof of concept for AAV-based gene therapy to humans is planned. C1 [Denard, Jerome; Marolleau, Beatrice; Jenny, Christine; Svinartchouk, Fedor] Genethon, Evry, France. [Rao, Tata Nageswara; Fehling, Hans Joerg] Univ Ulm, Inst Immunol, D-89069 Ulm, Germany. [Rao, Tata Nageswara] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Rao, Tata Nageswara] Joslin Diabet Ctr, Boston, MA 02215 USA. [Voit, Thomas] Univ Paris 06, INSERM, U974, UM76,CNRS,UMR7215,Inst Myol, Paris, France. RP Svinartchouk, F (reprint author), Genethon, Evry, France. EM svinart@genethon.fr FU Association Francaise contre les Myopathies (AFM) FX This work was supported by the Association Francaise contre les Myopathies (AFM). NR 53 TC 6 Z9 8 U1 0 U2 5 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 OCT PY 2013 VL 87 IS 19 BP 10784 EP 10791 DI 10.1128/JVI.01813-13 PG 8 WC Virology SC Virology GA 214WV UT WOS:000324169200033 PM 23903832 ER PT J AU Kloverpris, HN Stryhn, A Harndahl, M Payne, R Towers, GJ Chen, FB Riddell, L Walker, BD Ndung'u, T Leslie, A Buus, S Goulder, P AF Kloverpris, Henrik N. Stryhn, Anette Harndahl, Mikkel Payne, Rebecca Towers, Greg J. Chen, Fabian Riddell, Lynn Walker, Bruce D. Ndung'u, Thumbi Leslie, Alasdair Buus, Soren Goulder, Philip TI HLA-Specific Intracellular Epitope Processing Shapes an Immunodominance Pattern for HLA-B*57 That Is Distinct from HLA-B*58:01 SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; CLASS-I; IMMUNE CONTROL; ANTIGEN PRESENTATION; TYPE-1 INFECTION; PEPTIDE-BINDING; HIV; DETERMINANTS; ESCAPE AB HLA-B*57 is strongly associated with immune control of HIV and delayed AIDS progression. The closely related, but less protective, HLA-B*58:01 presents similar epitopes, but HLA-B*58:01(+) individuals do not generate CD8(+) T cells targeting the KF11-Gag epitope, which has been linked to low viremia. Here we show that HLA-B*58:01 binds and presents KF11 peptide, but HIV-infected HLA-B*58:01(+) cells fail to process KF11. This unexpected finding demonstrates that immunodominance patterns can be influenced by intracellular events independent of HLA binding motifs. C1 [Kloverpris, Henrik N.; Payne, Rebecca; Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. [Kloverpris, Henrik N.; Stryhn, Anette; Harndahl, Mikkel; Buus, Soren] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. [Chen, Fabian] Royal Berkshire Hosp, Dept Sexual Hlth, Reading RG1 5AN, Berks, England. [Riddell, Lynn] Northamptonshire Healthcare Natl Hlth Serv Trust, Northampton Gen Hosp, Dept Genitourinary Med, Northampton, England. [Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Program, Durban, South Africa. [Walker, Bruce D.; Goulder, Philip] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Towers, Greg J.] UCL, MRC, Ctr Med Mol Virol, Div Infect & Immun, London, England. [Kloverpris, Henrik N.; Leslie, Alasdair] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, K RITH, Nelson R Mandela Sch Med, Durban, South Africa. RP Kloverpris, HN (reprint author), Univ Oxford, Dept Paediat, Oxford, England. EM henrik.kloverpris@k-rith.org RI Buus, Soren/F-5446-2010; OI Buus, Soren/0000-0001-8363-1999; Towers, Gregory/0000-0002-7707-0264; Ndung'u, Thumbi/0000-0003-2962-3992 FU Wellcome Trust; National Institutes of Health [R01 AI46995]; Danish Agency for Science, Technology and Innovation [12-132295] FX This work was supported by the Wellcome Trust (P.G.) and the National Institutes of Health, grant R01 AI46995. H.N.K holds a grant from the Danish Agency for Science, Technology and Innovation, no. 12-132295. NR 24 TC 5 Z9 5 U1 0 U2 3 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 OCT PY 2013 VL 87 IS 19 BP 10889 EP 10894 DI 10.1128/JVI.01122-13 PG 6 WC Virology SC Virology GA 214WV UT WOS:000324169200042 PM 23864640 ER PT J AU Jin, J Limburg, S Joshi, SK Landman, R Park, M Zhang, Q Kim, HT Kuo, AC AF Jin, Jenny Limburg, Sonja Joshi, Sunil K. Landman, Rebeccah Park, Michelle Zhang, Qia Kim, Hubert T. Kuo, Alfred C. TI Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor SO TISSUE ENGINEERING PART A LA English DT Article ID INTRATHECAL DELIVERY-SYSTEM; HYALURONIC-ACID; SCIATIC-NERVE; CONTROLLED-RELEASE; NEURON OUTGROWTH; COLLAGEN MATRIX; AXONAL GROWTH; FIBER GROWTH; SPINAL-CORD; REGENERATION AB Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. C1 [Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.; Kuo, Alfred C.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA USA. [Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.; Kuo, Alfred C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Kuo, AC (reprint author), San Francisco VA Med Ctr, 4150 Clement St Box 112, San Francisco, CA 94121 USA. EM KuoAC@orthosurg.ucsf.edu FU Department of Defense [W81XWH-05-2-0094] FX We thank Professor Song Li and Shyam Patel for informative discussions, Bora Shin and Judy Shigenaga for technical assistance, and Eva Grotkopp for statistical assistance. This work was supported by the Department of Defense Grant (W81XWH-05-2-0094), which was administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California. NR 53 TC 8 Z9 10 U1 3 U2 91 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD OCT 1 PY 2013 VL 19 IS 19-20 BP 2138 EP 2146 DI 10.1089/ten.tea.2012.0575 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 211TI UT WOS:000323933400006 PM 23659607 ER PT J AU Jeng, L Hsu, HP Spector, M AF Jeng, Lily Hsu, Hu-Ping Spector, Myron TI Tissue-Engineered Cartilaginous Constructs for the Treatment of Caprine Cartilage Defects, Including Distribution of Laminin and Type IV Collagen SO TISSUE ENGINEERING PART A LA English DT Article ID CULTURED AUTOLOGOUS CHONDROCYTES; ARTICULAR-CARTILAGE; CANINE MODEL; GOAT MODEL; PERICELLULAR MATRIX; BASEMENT-MEMBRANES; CHONDRAL DEFECT; IN-VITRO; PERLECAN; REPAIR AB The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration. C1 [Jeng, Lily; Hsu, Hu-Ping; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Jeng, Lily] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Dept Orthopaed Surg, Sch Med, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, Mail Stop 151 Res 150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs; Department of Defense; National Science Foundation; Siebel Scholarship; VA Research Career Scientist Award FX This work was supported by the Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs; the Department of Defense; the National Science Foundation Graduate Research Fellowship (L. Jeng); and the Siebel Scholarship (L. Jeng). M. Spector was supported by a VA Research Career Scientist Award. NR 28 TC 8 Z9 8 U1 1 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD OCT 1 PY 2013 VL 19 IS 19-20 BP 2267 EP 2274 DI 10.1089/ten.tea.2013.0013 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 211TI UT WOS:000323933400018 PM 23672504 ER PT J AU Mbah, MLN Poolman, EM Drain, PK Coffee, MP van der Werf, MJ Galvani, AP AF Mbah, Martial L. Ndeffo Poolman, Eric M. Drain, Paul K. Coffee, Megan P. van der Werf, Marieke J. Galvani, Alison P. TI HIV and Schistosoma haematobium prevalences correlate in sub-Saharan Africa SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE HIV; genital schistosomiasis; sub-Saharan Africa; Schistosoma haematobium; Schistosoma mansoni; regression analysis ID FEMALE GENITAL SCHISTOSOMIASIS; RURAL ZIMBABWEAN WOMEN; RISK-FACTORS; UROGENITAL SCHISTOSOMIASIS; DEVELOPING-COUNTRIES; INFECTION; ASSOCIATION; COMMUNITIES; MORBIDITY; HIV/AIDS AB OBJECTIVE Epidemiological studies have observed that genital schistosomiasis increases the risk of HIV infection in Africa. We analysed the correlation between Schistosoma haematobium prevalence and HIV prevalence across sub-Saharan African countries. DESIGN Regression analysis of prevalence of HIV and S. haematobium across sub-Saharan African countries. METHODS Using compiled country-level S. haematobium prevalence, HIV prevalence and other demographic and economic data from published sources, we applied univariate and multivariate regression models to assess the correlations between S. haematobium prevalence and HIV prevalence while controlling for risk factors associated with each infection. RESULTS In 43 sub-Saharan African countries, the mean prevalence of S. haematobium was 22.4% [standard deviation (SD): 9.8%] and for HIV was 6.21% (SD: 5.71%). In multivariate analysis, adjusted for prevalence of male circumcision, years since a country's first HIV/AIDS diagnosis, geographical region and immunization coverage, each S. haematobium infection per 100 individuals was associated with a 2.9% (95% CI: 0.2-5.8%) relative increase in HIV prevalence. S. haematobium was not associated with Schistosoma mansoni, HSV-2, hepatitis C, malaria or syphilis. CONCLUSIONS Schistosoma haematobium prevalence was associated with HIV prevalence in sub-Saharan Africa. Controlling S. haematobium may be an effective means of reducing HIV transmission in sub-Saharan Africa. C1 [Mbah, Martial L. Ndeffo; Galvani, Alison P.] Yale Univ, Sch Publ Hlth, New Haven, CT 06510 USA. [Poolman, Eric M.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Drain, Paul K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Drain, Paul K.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Drain, Paul K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Cambridge, MA 02138 USA. [Coffee, Megan P.] Hop Univ Etat dHaiti, Port Au Prince, Haiti. [van der Werf, Marieke J.] KNCV TB Fdn, The Hague, Netherlands. [van der Werf, Marieke J.] Univ Amsterdam, CINIMA, Amsterdam, Netherlands. RP Mbah, MLN (reprint author), Yale Univ, Sch Publ Hlth, Suite 200,135 Coll St, New Haven, CT 06510 USA. EM martial.ndeffo-mbah@yale.edu OI Drain, Paul/0000-0003-3300-3817; van der Werf, Marieke J./0000-0001-8021-1358 FU Institute for Advanced Studies in Berlin; Notsew Orm Sands Foundation; Ventura County Medical Center; David Geffen School of Medicine at UCLA FX This research was funded by the Institute for Advanced Studies in Berlin and the Notsew Orm Sands Foundation and supported by the Ventura County Medical Center, affiliated with the David Geffen School of Medicine at UCLA. NR 34 TC 9 Z9 9 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2013 VL 18 IS 10 BP 1174 EP 1179 DI 10.1111/tmi.12165 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 213PC UT WOS:000324069100004 ER PT J AU Li, CG Lee, PS Gu, XX Sun, Y Zhang, E Csibi, A Li, J Priolo, C Guo, YN Wu, CL Blenis, J Xu, KF Henske, EP Levy, B Kwiatkowski, D Yu, JJ AF Li, Chenggang Lee, Po-Shun Gu, Xiaoxiao Sun, Yang Zhang, Erik Csibi, Alfredo Li, Jing Priolo, Carmen Guo, Yanan Wu, Chin-Lee Blenis, John Xu, Kai-Feng Henske, Elizabeth Petri Levy, Bruce Kwiatkowski, David Yu, Jane J. TI Estradiol and mTORC2 orchestrate to enhance prostaglandin biosynthesis and tumorigenesis in tuberous sclerosis complex SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Li, Chenggang; Lee, Po-Shun; Sun, Yang; Zhang, Erik; Priolo, Carmen; Guo, Yanan; Henske, Elizabeth Petri; Levy, Bruce; Kwiatkowski, David; Yu, Jane J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Gu, Xiaoxiao; Csibi, Alfredo; Li, Jing; Blenis, John] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Xu, Kai-Feng] Peking Union Med Coll, Beijing 100021, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2013 VL 73 SU 19 MA C59 DI 10.1158/1538-7445.FBCR13-C59 PG 2 WC Oncology SC Oncology GA V40RV UT WOS:000209496600149 ER PT J AU Baratta, MG Baratta, MG Liu, J Liu, J Zwang, Y Zwang, Y Zwang, Y Schinzel, A Schinzel, A Drapkin, R Drapkin, R Hahn, W Hahn, W Hahn, W Livingston, DM Livingston, DM AF Baratta, Maria Giuseppina Baratta, Maria Giuseppina Liu, Joyce Liu, Joyce Zwang, Yaara Zwang, Yaara Zwang, Yaara Schinzel, Anna Schinzel, Anna Drapkin, Ronny Drapkin, Ronny Hahn, William Hahn, William Hahn, William Livingston, David M. Livingston, David M. TI In tumor screening for novel targets in papillary serous ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Baratta, Maria Giuseppina; Liu, Joyce; Zwang, Yaara; Schinzel, Anna; Drapkin, Ronny; Hahn, William; Livingston, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baratta, Maria Giuseppina; Liu, Joyce; Zwang, Yaara; Schinzel, Anna; Drapkin, Ronny; Hahn, William; Livingston, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Zwang, Yaara; Hahn, William] Broad Inst, Cambridge, MA USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA IA3 DI 10.1158/1078-0432.OVCA13-IA3 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100135 ER PT J AU Drapkin, R AF Drapkin, Ronny TI Discovering the distal fallopian tube as the origin for high-grade serous ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA IA5 DI 10.1158/1078-0432.OVCA13-IA5 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100137 ER PT J AU Duraisamy, S Levanon, K Adelmant, G Piao, HY Liu, JC Matulonis, U Hirsch, M Marto, JA Drapkin, R AF Duraisamy, Sekhar Levanon, Keren Adelmant, Guillaume Piao, Huiying Liu, Joyce Matulonis, Ursula Hirsch, Michelle Marto, Jarrod A. Drapkin, Ronny TI TNFAIP2 is required for growth and migration of ovarian cancer cells and functions to regulate trafficking of receptor tyrosine kinases SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Duraisamy, Sekhar; Adelmant, Guillaume; Piao, Huiying; Liu, Joyce; Matulonis, Ursula; Marto, Jarrod A.; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Levanon, Keren] Chaim Sheba Med Ctr, Sheba Canc Res Ctr, Ramat Gan, Israel. [Hirsch, Michelle] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA A80 DI 10.1158/1078-0432.OVCA13-A80 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100066 ER PT J AU Gubbels, JAA Hultgren, EM Johnson, J Johnson, E Sachs, J Hirsch, MS Liu, JC Drapkin, R Egland, KA AF Gubbels, Jennifer A. A. Hultgren, Elizabeth M. Johnson, Jessica Johnson, Emily Sachs, Jeffrey Hirsch, Michelle S. Liu, Joyce Drapkin, Ronny Egland, Kristi A. TI Expression of Sushi Domain Containing 2 (SUSD2) in high-grade ovarian serous carcinoma correlated with increased longevity of patients SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Gubbels, Jennifer A. A.; Johnson, Jessica; Johnson, Emily] Augustana Coll, Sioux Falls, SD USA. [Hultgren, Elizabeth M.; Sachs, Jeffrey; Egland, Kristi A.] Univ S Dakota, Sanford Sch Med, Sanford Res, Sioux Falls, SD USA. [Hirsch, Michelle S.; Liu, Joyce; Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 1 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 OCT 1 PY 2013 VL 19 SU S MA A71 DI 10.1158/1078-0432.OVCA13-A71 PG 2 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100059 ER PT J AU Hung, HI Klein, OJ Jung, YY Kulkarni, KS Rueda, BR Foster, R Evans, CL AF Hung, Hsin-I Klein, Oliver J. Jung, Yookyung Kulkarni, Kashmira S. Rueda, Bo R. Foster, Rosemary Evans, Conor L. TI Mapping, targeting, and eliminating therapeutically unresponsive ovarian cancer with high content imaging and photodynamic therapy SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Hung, Hsin-I; Klein, Oliver J.; Jung, Yookyung; Evans, Conor L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kulkarni, Kashmira S.; Rueda, Bo R.; Foster, Rosemary] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 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 OCT 1 PY 2013 VL 19 SU S MA B44 DI 10.1158/1078-0432.OVCA13-B44 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100104 ER PT J AU Iwanicki, MP Novak, M Zervantonakis, IK Ince, TA Drapkin, R Brugge, JS AF Iwanicki, Marcin P. Novak, Marian Zervantonakis, Ioannis K. Ince, Tan A. Drapkin, Ronny Brugge, Joan S. TI Targeting mutant p53 and cell-cell adhesion in ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Iwanicki, Marcin P.; Zervantonakis, Ioannis K.; Brugge, Joan S.] Harvard Univ, Sch Med, Boston, MA USA. [Novak, Marian; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ince, Tan A.] Univ Miami, Miller Sch Med, Interdisciplinary Stem Cell Inst, Miami, FL 33136 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 1 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 OCT 1 PY 2013 VL 19 SU S MA A7 DI 10.1158/1078-0432.OVCA13-A7 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100006 ER PT J AU Karst, AM Jones, PM Vena, N Ligon, AH Liu, JF Hirsch, MS Etemadmoghadam, D Bowtell, DD Drapkin, R AF Karst, Alison M. Jones, Paul M. Vena, Natalie Ligon, Azra H. Liu, Joyce F. Hirsch, Michelle S. Etemadmoghadam, Dariush Bowtell, David D. Drapkin, Ronny TI Cyclin E1 deregulation occurs early during fallopian tube tumorigenesis and promotes secretory cell transformation SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Karst, Alison M.; Jones, Paul M.; Vena, Natalie; Liu, Joyce F.; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ligon, Azra H.; Hirsch, Michelle S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Etemadmoghadam, Dariush; Bowtell, David D.] Peter MacCallum Canc Ctr, East Melbourne, Australia. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA PR02 DI 10.1158/1078-0432.OVCA13-PR02 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100158 ER PT J AU Labidi-Galy, I Clauss, A Ng, V Duraisamy, S Elias, KM Bilal, E Davidowitz, RA Lu, YL Badalian-Very, G Piao, HY Kang, UB Ficarro, S Ganesan, S Mills, GB Marto, J Drapkin, R AF Labidi-Galy, Intidhar Clauss, Adam Ng, Vivian Duraisamy, Sekhar Elias, Kevin M. Bilal, Erhan Davidowitz, Rachel A. Lu, Yiling Badalian-Very, Gayane Piao, Hui-Ying Kang, Un-Beom Ficarro, Scott Ganesan, Shridar Mills, Gordon B. Marto, Jarrod Drapkin, Ronny TI Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Labidi-Galy, Intidhar; Clauss, Adam; Ng, Vivian; Duraisamy, Sekhar; Badalian-Very, Gayane; Piao, Hui-Ying; Kang, Un-Beom; Ficarro, Scott; Marto, Jarrod; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Elias, Kevin M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bilal, Erhan; Ganesan, Shridar] Canc Inst New Jersey, Brunswick, NJ USA. [Davidowitz, Rachel A.] Harvard Univ, Sch Med, Boston, MA USA. [Lu, Yiling; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA B74 DI 10.1158/1078-0432.OVCA13-B74 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100127 ER PT J AU Labidi-Galy, I Elias, KM Vitonis, AF Hornick, JL Doyle, LA Hirsch, MS Cramer, DW Drapkin, R AF Labidi-Galy, Intidhar Elias, Kevin M. Vitonis, Allison F. Hornick, Jason L. Doyle, Leona A. Hirsch, Michelle S. Cramer, Daniel W. Drapkin, Ronny TI Common links suggest a shared embryologic origin for pancreatic and ovarian mucinous tumors SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Labidi-Galy, Intidhar; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Elias, Kevin M.; Vitonis, Allison F.; Hornick, Jason L.; Doyle, Leona A.; Hirsch, Michelle S.; Cramer, Daniel W.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA A11 DI 10.1158/1078-0432.OVCA13-A11 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100010 ER PT J AU Liu, SB Yang, JZ May, T Hua, YY Lu, S Elias, K Drapkin, R Welch, W Crum, C Berkowitz, RS Ng, SW AF Liu, Shubai Yang, Junzheng May, Taymaa Hua, Yuanyuan Lu, Shi Elias, Kevin Drapkin, Ronny Welch, William Crum, Christopher Berkowitz, Ross S. Ng, Shu-Wing TI The role of C-Terminal Binding Proteins in BRCA1 silencing and genetic instability of ovarian cancer cells SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Liu, Shubai; Yang, Junzheng; May, Taymaa; Hua, Yuanyuan; Lu, Shi; Elias, Kevin; Welch, William; Crum, Christopher; Berkowitz, Ross S.; Ng, Shu-Wing] Brigham & Womens Hosp, Boston, MA 02115 USA. [Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA B29 DI 10.1158/1078-0432.OVCA13-B29 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100095 ER PT J AU Moran-Jones, K Murali, R Chang, DK Wong, CW Spong, SM Hacker, NF Mok, SC Birrer, MJ Samimi, G AF Moran-Jones, Kim Murali, Rajmohan Chang, David K. Wong, Carol W. Spong, Suzanne M. Hacker, Neville F. Mok, Samuel C. Birrer, Michael J. Samimi, Goli TI Connective tissue growth factor (CTGF) as a novel therapeutic target in high grade serous ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Moran-Jones, Kim; Chang, David K.; Samimi, Goli] Garvan Inst Med Res, Sydney, NSW, Australia. [Murali, Rajmohan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wong, Carol W.; Spong, Suzanne M.] FibroGen Inc, San Francisco, CA USA. [Hacker, Neville F.] Royal Hosp Women, Randwick, NSW, Australia. [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA B58 DI 10.1158/1078-0432.OVCA13-B58 PG 2 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100113 ER PT J AU Naffar-Abu Amara, S Selfors, LM Krohn, M Ince, TA Rueda, BR Foster, R Mills, GB Brugge, JS AF Naffar-Abu Amara, Suha Selfors, Laura M. Krohn, Marit Ince, Tan A. Rueda, Bo R. Foster, Rosemary Mills, Gordon B. Brugge, Joan S. TI Cellular heterogeneity of ovarian carcinoma cells and its impact on tumor behavior SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Naffar-Abu Amara, Suha; Selfors, Laura M.; Brugge, Joan S.] Harvard Univ, Sch Med, Boston, MA USA. [Krohn, Marit; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ince, Tan A.] Univ Miami, Miami, FL USA. [Rueda, Bo R.; Foster, Rosemary] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA PR09 DI 10.1158/1078-0432.OVCA13-PR09 PG 1 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100165 ER PT J AU Wyant, GA Perets, R Muto, K Poole, BB Chen, JYH Ohman, AW Setlur, SR Crum, CP Drapkin, R Dinulescu, DM AF Wyant, Gregory A. Perets, Ruth Muto, Katherine Poole, Barish B. Chen, Jin Y. H. Ohman, Anders W. Setlur, Sunita R. Crum, Christopher P. Drapkin, Ronny Dinulescu, Daniela M. TI Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in BRCA/P53 models SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 [Wyant, Gregory A.; Muto, Katherine; Poole, Barish B.; Chen, Jin Y. H.; Ohman, Anders W.; Setlur, Sunita R.; Crum, Christopher P.; Drapkin, Ronny; Dinulescu, Daniela M.] Harvard Univ, Sch Med, Eugene Braunwald Res Ctr, Boston, MA USA. [Perets, Ruth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wyant, Gregory A.; Perets, Ruth; Muto, Katherine; Poole, Barish B.; Chen, Jin Y. H.; Ohman, Anders W.; Setlur, Sunita R.; Crum, Christopher P.; Drapkin, Ronny; Dinulescu, Daniela M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2013 VL 19 SU S MA PR01 DI 10.1158/1078-0432.OVCA13-PR01 PG 2 WC Oncology SC Oncology GA V40RQ UT WOS:000209496100157 ER PT J AU Horning, SM Wilkins, SS Dhanani, S Henriques, D AF Horning, Sheena M. Wilkins, Stacy S. Dhanani, Shawkat Henriques, Donna TI A Case of Elder Abuse and Undue Influence: Assessment and Treatment From a Geriatric Interdisciplinary Team SO CLINICAL CASE STUDIES LA English DT Article DE elder abuse; undue influence; dementia; decision-making capacity ID UNITED-STATES; MISTREATMENT; PREVALENCE AB Elder abuse is a pervasive problem that can have lasting emotional and physical consequences, increasing its victims' risk of mortality. Healthcare providers are frequently involved in the detection and intervention of elder abuse. Because of the complexity of these cases, applying treatment interventions within an interdisciplinary care team has been recommended to ensure older adults' safety and welfare. Psychologists in particular are frequently relied upon in these situations because of their expertise in cognitive, psychiatric, and capacity assessment, as well as their ability to intervene in a variety of difficult situations. The following is a report examining the case of Mr. B, who was a victim of elder abuse involving financial exploitation and undue influence. Assessment and treatment interventions were used within the context of an interdisciplinary care team, using a bio-psychosocial approach. A decision-tree model describing the steps to take in assessing and treating financial elder abuse is proposed. C1 [Horning, Sheena M.; Wilkins, Stacy S.; Dhanani, Shawkat; Henriques, Donna] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90025 USA. [Wilkins, Stacy S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Dhanani, Shawkat] Univ Calif Los Angeles, Los Angeles, CA USA. RP Horning, SM (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychol, 11301 Wilshire Blvd, Los Angeles, CA 90025 USA. EM Sheena.Horning@va.gov OI Horning, Sheena/0000-0002-9704-0070 NR 23 TC 1 Z9 1 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-6501 EI 1552-3802 J9 CLIN CASE STUD JI Clin. Case Stud. PD OCT PY 2013 VL 12 IS 5 BP 373 EP 387 DI 10.1177/1534650113496143 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW9OT UT WOS:000346587700004 ER PT J AU Biederman, J AF Biederman, J. TI Examining the nature of the comorbidity between pediatric attention-deficit/hyperactivity disorder and posttraumatic stress disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.4.f.002 BP S531 EP S532 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200730 ER PT J AU Biederman, J AF Biederman, J. TI Can autistic traits be identified in children with ADHD? A controlled study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.7.b.002 BP S586 EP S587 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200820 ER PT J AU Biederman, J AF Biederman, J. TI Can pediatric bipolar-I disorder be diagnosed in the context of posttraumatic stress disorder? A familial risk analysis SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.2.d.002 BP S363 EP S363 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200459 ER PT J AU Busner, J Kott, A Sachs, G AF Busner, J. Kott, A. Sachs, G. TI Increasing signal over noise in MDD clinical trials: improvement after efficacy scale rater training among experienced MDD investigators SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Busner, J.] Penn State Coll Med & Bracket, Psychiat, Wayne, NJ USA. [Kott, A.] Bracket, Data Analyt, Prague, Czech Republic. [Sachs, G.] Bracket, Lexington, KY 40509 USA. [Sachs, G.] Massachusetts Gen Hosp, Psychiat, Lexington, MA 02421 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.2.b.049 BP S348 EP S348 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200434 ER PT J AU Hansen, HD Mandeville, J Feng, L Sander, CY Hooker, JM Catana, C Rosen, B Knudsen, GM AF Hansen, H. D. Mandeville, J. Feng, L. Sander, C. Y. Hooker, J. M. Catana, C. Rosen, B. Knudsen, G. M. TI Simultaneous PET-MR imaging of the effects of microdose challenges using [C-11]AZ-10419369 in non-human primates SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Hansen, H. D.; Feng, L.; Knudsen, G. M.] Copenhagen Univ Hosp, Rigshosp, Ctr Integrated Mol Brain Imaging, Copenhagen, Denmark. [Mandeville, J.; Sander, C. Y.; Hooker, J. M.; Catana, C.; Rosen, B.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RI Hansen, Hanne Demant/C-9029-2013 OI Hansen, Hanne Demant/0000-0001-5564-7627 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.1.i.024 BP S277 EP S277 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200318 ER PT J AU Herbert, MR AF Herbert, M. R. TI Autism: from static genetic brain defect to dynamic gene-environment modulated pathophysiology SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Herbert, M. R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Neurol, Charlestown, MA USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA S.01.03 BP S111 EP S112 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200010 ER PT J AU Jeon, HJ Woo, JM Lee, SH Kim, EJ Chung, SH Ha, JH Fava, M Mischoulon, D Kim, JH Yu, BH AF Jeon, H. J. Woo, J. M. Lee, S. H. Kim, E. J. Chung, S. H. Ha, J. H. Fava, M. Mischoulon, D. Kim, J. H. Yu, B. H. TI Improvement in subjective and objective neurocognitive functions in patients with major depressive disorder: tianeptine versus escitalopram SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Jeon, H. J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat, Seoul, South Korea. [Woo, J. M.] Inje Univ, Seoul Paik Hosp, Sch Med, Dept Psychiat, Seoul, South Korea. [Lee, S. H.] Inje Univ, Ilsan Paik Hosp, Sch Med, Dept Psychiat, Ilsan, South Korea. [Kim, E. J.] Eulji Univ, Sch Med, Eulji Gen Hosp, Dept Psychiat, Seoul, South Korea. [Chung, S. H.] Univ Ulsan, Coll Med, Dept Psychiat, Asan Med Ctr, Seoul, South Korea. [Ha, J. H.] Konkuk Univ, Sch Med, Dept Psychiat, Seoul, South Korea. [Fava, M.; Mischoulon, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Kim, J. H.; Yu, B. H.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat, Seoul, South Korea. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.2.b.004 BP S320 EP S321 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200389 ER PT J AU Joshi, G Wozniak, J Petty, C Fried, R Galdo, M McDermott, K Epstein, C Walker, R Feinberg, LK Biederman, J AF Joshi, G. Wozniak, J. Petty, C. Fried, R. Galdo, M. McDermott, K. Epstein, C. Walker, R. Feinberg, L. K. Biederman, J. TI Ascertainment source and clinical correlates of autism spectrum disorders (ASD): a comparative study of ASD youth attending a specialty and a general psychiatry clinic SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Joshi, G.; Wozniak, J.; Petty, C.; Fried, R.; Biederman, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat, Boston, MA USA. [Galdo, M.; McDermott, K.; Epstein, C.; Walker, R.; Feinberg, L. K.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.7.b.010 BP S591 EP S592 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200828 ER PT J AU Ketter, TA Sachs, GS Lu, K Ruth, A Laszlovszky, I Nagy, K Starace, A Durgam, S AF Ketter, T. A. Sachs, G. S. Lu, K. Ruth, A. Laszlovszky, I. Nagy, K. Starace, A. Durgam, S. TI Long-term safety and tolerability of open-label cariprazine in patients with bipolar I disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Ketter, T. A.] Stanford Univ, Sch Med, Dept Psychiat & Behav, Stanford, CA 94305 USA. [Sachs, G. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lu, K.; Starace, A.; Durgam, S.] Forest Res Inst, Jersey City, NJ 07311 USA. [Ruth, A.] Prescott Med Commun Grp, Chicago, IL USA. [Laszlovszky, I.; Nagy, K.] Gedeon Richter Plc, Budapest, Hungary. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.2.d.024 BP S377 EP S377 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200481 ER PT J AU Sachs, G Daniel, D Dries, J AF Sachs, G. Daniel, D. Dries, J. TI Could a simplified PANSS be more efficient? SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 [Sachs, G.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sachs, G.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Daniel, D.] Bracket, Washington, DC USA. [Dries, J.] Bracket, Wayne, NJ USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2013 VL 23 SU 2 MA P.3.f.026 BP S506 EP S507 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA V40HR UT WOS:000209470200690 ER PT J AU Casey, JD Moromizato, T Gibbons, FK Christopher, KB AF Casey, J. D. Moromizato, T. Gibbons, F. K. Christopher, K. B. TI THE ASSOCIATION OF HOSPITAL ADMISSION SERUM ALBUMIN AND POST HOSPITAL DISCHARGE MORTALITY IN ICU SURVEAORS: A REGISTRY BASED COHORT STUDY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Casey, J. D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Moromizato, T.; Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0227 BP S276 EP S277 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431600224 ER PT J AU Chhangani, SV AF Chhangani, S. V. TI SETTING UP TELEMEDICINE CRITICAL CARE SERVICE AT A CRITICAL ACCESS HOSPITAL IN THE UNITED STATES SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Chhangani, S. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chhangani, S. V.] Marthas Vineyard Hosp, Oak Bluffs, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0922 BP S472 EP S472 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431601216 ER PT J AU Ehrmann, S Roche-Campo, F Contentin, I Razazi, K Donzeau, A Thevoz, D Dugemier, J Jochmans, S Edelson, A Papanikolaou, M Yoshido, HL Arnal, JM Curiel-Balsera, E Besbes, M Gonzalez, R Daroui, I Apiou-Sbirlea, G Isabey, D Brochard, L AF Ehrmann, S. Roche-Campo, F. Contentin, I. Razazi, K. Donzeau, A. Thevoz, D. Dugemier, J. Jochmans, S. Edelson, A. Papanikolaou, M. Yoshido, H. Leon Arnal, J-M Curiel-Balsera, E. Besbes, M. Gonzalez, R. Daroui, I. Apiou-Sbirlea, G. Isabey, D. Brochard, L. CA AT ICU Study Grp TI AEROSOL-THERAPY IN THE INTENSIVE CARE UNIT: A TWO WEEKS CROSS SECTIONAL STUDY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Ehrmann, S.; Contentin, I.] CHRU, Serv Reanimat Polyvalente, Tours, France. [Ehrmann, S.; Apiou-Sbirlea, G.; Isabey, D.; Brochard, L.] Hop Henri Mondor, INSERM, UMR 955, Equipe Biomecan Cellulaire & Resp, F-94010 Creteil, France. [Ehrmann, S.; Apiou-Sbirlea, G.] Univ Paris Est, Fac Med, Creteil, France. [Roche-Campo, F.] Hosp Santa Creu & Sant Pau, Serv Med Intens, Barcelona, Spain. [Contentin, I.] Ctr Hosp Univ Cochin, AP HP, Serv Reanimat Med, Paris, France. [Razazi, K.] Grp Hosp Henri Mondor, AP HP, Serv Reanimat Med, Paris, France. [Donzeau, A.] CHU Angers, Serv Reanimat Med & Med Hyperbare, Angers, France. [Thevoz, D.] CHU Vaudois, Serv Med Intens Adulte, CH-1011 Lausanne, Switzerland. [Thevoz, D.] CHU Vaudois, Ctr Brules, CH-1011 Lausanne, Switzerland. [Dugemier, J.] Clin Univ St Luc, Intens Care Unit, B-1200 Brussels, Belgium. [Jochmans, S.] Ctr Hosp Marc Sacquet, Serv Reanimat, Melun, France. [Edelson, A.] Ctr Hosp Taaone, Serv Reanimat, Pirae, Fr Polynesia. [Papanikolaou, M.] Hippocrate Gen Hosp Athens, Intens Care Unit, Athens, Greece. [Yoshido, H. Leon] Hosp Nacl Edgardo Rebagliati Martins ESSALUD, Unidad Cuidados Intens, Lima, Peru. [Arnal, J-M] Hop St Musse, Serv Reanimat Polyvalente, Toulon, France. [Curiel-Balsera, E.] Hosp Reg Univ Carlos Haya, Unidad Cuidados Intens, Malaga, Spain. [Besbes, M.] Hosp A Mami, Intens Care Unit, Ariana, Tunisia. [Gonzalez, R.] Hosp Gen Univ Gregorio Maranon, Madrid, Spain. [Daroui, I.] Osped Sacrocuore Don Calabria, Dipartimento Anestesia Rianimaz, Negrar, Italy. [Apiou-Sbirlea, G.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Apiou-Sbirlea, G.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Apiou-Sbirlea, G.] Boston Univ, Sch Med, Boston, MA USA. [Isabey, D.] Univ Paris Est, Fac Med, Creteil, France. [Isabey, D.] Hop Henri Mondor, CNRS, ERL 7240, Equipe Biomecan Cellulaire & Resp, F-94010 Creteil, France. [Brochard, L.] Hop Cantonal Univ Geneva, Serv Soins Intensifs, Geneva, Switzerland. [Brochard, L.] Univ Geneva, Fac Med, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0573 BP S376 EP S377 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431600572 ER PT J AU Lee-Sarwar, KA Gibbons, FK Christopher, KB AF Lee-Sarwar, K. A. Gibbons, F. K. Christopher, K. B. TI VIP STATUS AND OUTCOMES OF CRITICAL CARE SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Lee-Sarwar, K. A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0252 BP S284 EP S284 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431600252 ER PT J AU Okamoto, H Kuriyama, A Fukuoka, T Hasegawa, K AF Okamoto, H. Kuriyama, A. Fukuoka, T. Hasegawa, K. CA Japanese Emergency Med Network TI REPEATED INTUBATION ATTEMPTS AND FEMALE SEX ARE ASSOCIATED WITH ADVERSE EVENTS DURING EMERGENCY INTUBATION EN THE EMERGENCY DEPARTMENTS: AN ANALYSIS FROM A MULTICENTER PROSPECTIVE OBSERVATIONAL STUDY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Okamoto, H.; Kuriyama, A.; Fukuoka, T.] Kurashiki Cent Hosp, Kurashiki, Okayama, Japan. [Hasegawa, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0682 BP S406 EP S406 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431600680 ER PT J AU Purtle, SW McKane, CK Gibbons, FK Christopher, KB AF Purtle, S. W. McKane, C. K. Gibbons, F. K. Christopher, K. B. TI THE ASSOCIATION OF RED CELL DISTRIBUTION WIDTH AT HOSPITAL DISCHARGE IN CRITICAL ILLNESS SURVIVORS AND HOSPITAL READMISSION: A REGISTRY BASED COHORT STUDY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Purtle, S. W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [McKane, C. K.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0661 BP S401 EP S401 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431600660 ER PT J AU Stehman, CR Moromizato, T McKane, CK Mogensen, KM Gibbons, FK Christopher, KB AF Stehman, C. R. Moromizato, T. McKane, C. K. Mogensen, K. M. Gibbons, F. K. Christopher, K. B. TI ASSOCIATION BETWEEN BLOOD ALCOHOL CONCENTRATION AND MORTALITY IN CRITICAL ILLNESS SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Stehman, C. R.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Stehman, C. R.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Moromizato, T.; Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [McKane, C. K.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Mogensen, K. M.] Brigham & Womens Hosp, Dept Nutr, Boston, MA 02115 USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0315 BP S301 EP S302 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431600312 ER PT J AU Thickett, DR Moromizato, T Litonjua, AA Amrein, K Quraishi, SA Lee-Sarwar, KA Gibbons, FK Camargo, CA Giovannucci, E Christopher, KB AF Thickett, D. R. Moromizato, T. Litonjua, A. A. Amrein, K. Quraishi, S. A. Lee-Sarwar, K. A. Gibbons, F. K. Camargo, C. A., Jr. Giovannucci, E. Christopher, K. B. TI ASSOCIATION OF LOW SERUM 25-HYDROXYVITAMIN D LEVELS AND NON-CARDIOGENIC ACUTE RESPIRATORY FAILURE SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT ESICM 26th Annual Congress CY OCT 05-09, 2013 CL Paris, FRANCE SP ESICM C1 [Thickett, D. R.] Univ Birmingham, Sch Clin & Expt Med, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Moromizato, T.; Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Litonjua, A. A.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Amrein, K.] Med Univ Graz, Div Endocrinol & Metab, Graz, Austria. [Quraishi, S. A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Lee-Sarwar, K. A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2013 VL 39 SU 2 MA 0983 BP S489 EP S489 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AP9WI UT WOS:000342431601276 ER PT J AU Kociol, RD Hammill, BG Fonarow, GC Heidenreich, PA Go, AS Peterson, ED Curtis, LH Hernandez, AF AF Kociol, Robb D. Hammill, Bradley G. Fonarow, Gregg C. Heidenreich, Paul A. Go, Alan S. Peterson, Eric D. Curtis, Lesley H. Hernandez, Adrian F. TI Associations Between Use of the Hospitalist Model and Quality of Care and Outcomes of Older Patients Hospitalized for Heart Failure SO JACC-HEART FAILURE LA English DT Article DE heart failure; hospitalists; Medicare; outcome assessment (health care) AB Objectives This study sought to examine the associations of hospitalist and cardiologist care of patients with heart failure with outcomes and adherence to quality measures. Background The hospitalist model of inpatient care has grown nationally, but its associations with quality of care and outcomes of patients hospitalized with heart failure are not known. Methods We analyzed data from the Get With the Guidelines-Heart Failure registry linked to Medicare claims for 2005 through 2008. For each hospital, we calculated the percentage of heart failure hospitalizations for which a hospitalist was the attending physician. We examined outcomes and care quality for patients stratified by rates of hospitalist use. Using multivariable models, we estimated associations between hospital-level use of hospitalists and cardiologists and 30-day risk-adjusted outcomes and adherence to measures of quality care. Results The analysis included 31,505 Medicare beneficiaries in 166 hospitals. Across hospitals, the use of hospitalists varied from 0% to 83%. After multivariable adjustment, a 10% increase in the use of hospitalists was associated with a slight increase in mortality (risk ratio: 1.03; 95% confidence interval [CI]: 1.00 to 1.06) and decrease in length of stay (0.09 days; 95% CI: 0.02 to 0.16). There was no association with 30-day readmission. Increased use of hospitalists in hospitals with high use of cardiologists was associated with improved defect-free adherence to a composite of heart failure performance measures (risk ratio: 1.03; 95% CI: 1.01 to 1.06). Conclusions Hospitalist care varied significantly across hospitals for heart failure admissions and was not associated with improved 30-day outcomes. Comanagement by hospitalists and cardiologists may help to improve adherence to some quality measures, but it remains unclear what care model improves 30-day clinical outcomes. (J Am Coll Cardiol HF 2013; 1: 445-53) (C) 2013 by the American College of Cardiology Foundation C1 [Kociol, Robb D.; Peterson, Eric D.; Curtis, Lesley H.; Hernandez, Adrian F.] Harvard Univ, Beth Israel Deaconess Med Ctr, CardioVasc Inst, Sch Med, Boston, MA 02215 USA. [Hammill, Bradley G.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Heidenreich, Paul A.] Stanford Univ, Sch Med, Palo Alto Vet Affairs Med Ctr, Div Cardiol,Dept Med, Stanford, CA 94305 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peterson, Eric D.; Curtis, Lesley H.; Hernandez, Adrian F.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. RP Kociol, RD (reprint author), Beth Israel Deaconness Med Ctr, 471 Brookline Ave, Boston, MA 02215 USA. EM rkociol@bidmc.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Heidenreich, Paul/0000-0001-7730-8490; Hernandez, Adrian F./0000-0003-3387-9616 NR 25 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD OCT PY 2013 VL 1 IS 5 BP 445 EP 453 DI 10.1016/j.jchf.2013.07.001 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41GY UT WOS:000209535900012 PM 24621978 ER PT J AU Latronico, N Nisoli, E Eikermann, M AF Latronico, Nicola Nisoli, Enzo Eikermann, Matthias TI Muscle weakness and nutrition in critical illness: matching nutrient supply and use SO LANCET RESPIRATORY MEDICINE LA English DT Editorial Material ID PARENTERAL-NUTRITION; CALORIE RESTRICTION C1 [Latronico, Nicola] Univ Brescia, Spedali Civili, Dept Anaesthesia & Crit Care Med, I-25123 Brescia, Italy. [Nisoli, Enzo] Univ Milan, Ctr Study & Res Obes, Dept Med Biotechnol & Translat Med, Milan, Italy. [Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Crit Care & Pain Med, Boston, MA USA. [Eikermann, Matthias] Essen Duisburg Univ, Klin Fuer Anaesthesiol & Intens Med, Essen, Germany. RP Latronico, N (reprint author), Univ Brescia, Spedali Civili, Dept Anaesthesia & Crit Care Med, Piazzale Osped Civili 1, I-25123 Brescia, Italy. EM nicola.latronico@med.unibs.it RI Latronico, Nicola/F-1557-2010 OI Latronico, Nicola/0000-0002-2521-5871 NR 11 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD OCT PY 2013 VL 1 IS 8 BP 589 EP 590 DI 10.1016/S2213-2600(13)70148-6 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ3KC UT WOS:000342690300007 PM 24461653 ER PT J AU Faber, AC Vora, S Engelman, JA AF Faber, Anthony C. Vora, Sadhna Engelman, Jeffrey A. TI Sensitizing low BIM expressing breast cancers to targeted therapies SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract C1 [Faber, Anthony C.; Vora, Sadhna; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2013 VL 11 SU 10 MA A062 DI 10.1158/1557-3125.ADVBC-A062 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA V40OL UT WOS:000209487800038 ER PT J AU Thakkar, A Santagata, S Ergonul, A Wang, B Woo, T Hu, R Harrell, JC McNamara, G Schwede, M Culhane, AC Kindelberger, D Rodig, S Richardson, A Schnitt, SJ Tamimi, RM Ince, TA AF Thakkar, Ankita Santagata, Sandro Ergonul, Ayse Wang, Bin Woo, Terri Hu, Rong Harrell, J. Chuck McNamara, George Schwede, Matthew Culhane, Aedin C. Kindelberger, David Rodig, Scott Richardson, Andrea Schnitt, Stuart J. Tamimi, Rulla M. Ince, Tan A. TI Taxonomy of breast cancer based on normal cell phenotype and ontology SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract C1 [Thakkar, Ankita; Ergonul, Ayse; Wang, Bin; McNamara, George; Ince, Tan A.] Univ Miami, Miami, FL USA. [Santagata, Sandro; Woo, Terri; Kindelberger, David; Rodig, Scott; Richardson, Andrea] Brigham & Womens Hosp, Boston, MA 02115 USA. [Santagata, Sandro; Woo, Terri; Schwede, Matthew; Culhane, Aedin C.; Kindelberger, David; Rodig, Scott; Richardson, Andrea] Harvard Univ, Sch Med, Boston, MA USA. [Hu, Rong; Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Harrell, J. Chuck] Univ N Carolina, Chapel Hill, NC USA. [Schwede, Matthew; Culhane, Aedin C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schnitt, Stuart J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2013 VL 11 SU 10 MA B067 DI 10.1158/1557-3125.ADVBC-B067 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA V40OL UT WOS:000209487800123 ER PT J AU Vora, S Elkabets, M Kim, N Costa, C Liu, M Li, XY Cao, A Schlegel, R Scaltriti, M Baselga, J Huang, A Engelman, JA AF Vora, Sadhna Elkabets, Moshe Kim, Nayoon Costa, Carlotta Liu, Manway Li Xiaoyan Cao, Alex Schlegel, Robert Scaltriti, Maurizio Baselga, Jose Huang, Alan Engelman, Jeffrey A. TI Overcoming resistance to PI3K inhibitors in breast cancer: Results of a pooled shRNA screen and combinatorial drug screen SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract C1 [Vora, Sadhna; Kim, Nayoon; Costa, Carlotta; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Elkabets, Moshe; Scaltriti, Maurizio; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Liu, Manway; Li Xiaoyan; Cao, Alex; Schlegel, Robert; Huang, Alan] Novartis Inst BioMed Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2013 VL 11 SU 10 MA PR06 DI 10.1158/1557-3125.ADVBC-PR06 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA V40OL UT WOS:000209487800179 ER PT J AU Zhang, Y Schroeder, BE Jerevall, PL Stal, O Sgroi, DC Erlander, MG Schnabel, CA AF Zhang, Yi Schroeder, Brock E. Jerevall, Piiha-Lotta Stal, Olle Sgroi, Dennis C. Erlander, Mark G. Schnabel, Catherine A. TI Prediction of the clinical benefit of adjuvant tamoxifen therapy using Breast Cancer Index (HOXB13:IL17BR) SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhang, Yi; Schroeder, Brock E.; Erlander, Mark G.; Schnabel, Catherine A.] BioTheranostics Inc, San Diego, CA USA. [Jerevall, Piiha-Lotta; Sgroi, Dennis C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stal, Olle] Linkoping Univ, Linkoping, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2013 VL 11 SU 10 MA B031 DI 10.1158/1557-3125.ADVBC-B031 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA V40OL UT WOS:000209487800104 ER PT J AU Rinker, JR Cossey, TC Cutter, GR Culpepper, WJ AF Rinker, John R., II Cossey, Tiffany C. Cutter, Gary R. Culpepper, William J. TI A retrospective review of lithium usage in veterans with multiple sclerosis SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Review DE Multiple sclersosi; Lithium; Veteran; Retrospective study; Drug toxicity; Drug tolerance AB Objective: Lithium (Li) reduces disease activity in animal models of multiple sclerosis (MS), but has not been previously studied in human MS. While developing a clinical trial to test the effects of Li in MS, we performed a retrospective chart review to determine the safety and tolerability of Li among US veterans with MS. Methods: We identified all veterans with MS prescribed Li from 1998 to 2009 using the Department of Veterans Affairs Pharmacy Benefits Management. Charts were reviewed for Li-related adverse events and effects on the MS disease course. Results: Among 21,847 veterans with MS, 101 met inclusion criteria and took Li >6 months. Eighteen percent of subjects experienced a Li-associated adverse event. Later age of MS onset was associated with increased risk of Li-related adverse events (p=0.004). Associations between Li use and MS disease activity were mixed: Li was not associated with increased risk of enhancing MRI lesions (p=0.655), but annualized relapse rates were higher on Li (0.34 vs. 0.20, p=0.044). In contrast, change in Expanded Disability Status Scale scores was greater in the off-Li period than the on-Li period (0.8 vs. 0.3, p=0.003). Conclusion: Adverse events occur in a minority of Li-treated MS patients. A consistent effect of Li on MS disease activity was not apparent. These findings indicate a clinical trial will be needed to ascertain Lis effects on the MS disease course. Published by Elsevier B.V. C1 [Rinker, John R., II; Cossey, Tiffany C.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Rinker, John R., II] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Cossey, Tiffany C.] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL 35294 USA. [Cutter, Gary R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Culpepper, William J.] Baltimore VA Med Ctr, VA Multiple Sclerosis Ctr Excellence East, Baltimore, MD 20201 USA. RP Rinker, JR (reprint author), Univ Alabama Birmingham, SC 440,1720 7th Ave South, Birmingham, AL 35233 USA. EM rinkerj@uab.edu FU Department of Veterans Affairs Career Development Award (CDA2); VA MS Center of Excellence East FX Dr. John Rinker is supported by a Department of Veterans Affairs Career Development Award (CDA2).; Dr. Joel Culpepper is supported by the VA MS Center of Excellence East. He reports no conflicts in regards to this work. NR 25 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-0348 EI 2211-0356 J9 MULT SCLER RELAT DIS JI Mult. Scler. Relat. Disord. PD OCT PY 2013 VL 2 IS 4 BP 327 EP 333 DI 10.1016/j.msard.2013.03.004 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA V37LE UT WOS:000209276500007 PM 25877842 ER PT J AU Zhao, S Cao, L Freeman, JW AF Zhao, S. Cao, L. Freeman, J. W. TI Knockdown of RON receptor kinase delays but does not prevent tumor progression while enhancing HGF/MET signaling in pancreatic cancer cell lines SO ONCOGENESIS LA English DT Article DE RON; MET; pancreatic cancer; cancer therapy AB In this study, the role of RON (receptor originated from nantes) in tumor progression was further investigated in context with MET expression and activity. RON and MET expressions were not detected in an immortalized normal human pancreas cell line (HPNE), but were co-expressed in five of seven pancreatic ductal adenocarcinoma (PDAC) cell lines (PANC-1, BxPC-3, Capan-2, CFPAC-1 and AsPC-1). RON expression was knocked down by an shRNA approach in two PDAC cell lines (BxPC-3 and CFPAC-1) that co-express MET. Knockdown of RON significantly inhibited cell growth, clonogenicity and macrophage stimulating protein (MSP), RON ligand induced invasion by in vitro assays and significantly inhibited tumor growth (P<0.001) and metastasis (P<0.009) in an orthotopic pancreatic cancer mouse model at week 7. However, by week 9, the mice implanted with RON knockdown cells had developed similar size primary tumors and metastases compared with that seen in the control group at week 7. Western blotting and immunohistochemistry analyses showed that MET remains highly expressed in cells and tumor tissues where RON was knocked down. Moreover, knockdown of RON did not prevent hepatocyte growth factor (HGF) stimulated invasion in in vitro Matrigel assays. Treating cells with MSP induced the transphosphorylation of MET, suggesting that signaling may be modulated by relative levels of RON and MET receptors and their corresponding ligands. To this point, HGF treatment of RON knockdown cells caused an increase in intensity and duration of MET signaling, suggesting that MET signaling may compensate for loss of RON signaling. Treatment of cells with an MET inhibitor, PHA-665752, had minimal effects on inhibiting cell growth but significantly inhibited cell invasion induce by ligands for either MET or RON. These results suggest that HGF/MET signaling may have a more important role in tumor cell invasion and metastasis rather than in tumor cell proliferation. This study indicates that specific inhibition of RON delays but does not prevent progression of PDAC. Moreover, specific signaling may be modulated by the interaction of RON and MET receptors. This dynamic interaction of RON and MET in pancreatic cancer cells suggests that dual targeting of both RON and MET will be preferable to inhibition of either target alone. C1 [Zhao, S.; Cao, L.; Freeman, J. W.] Univ Texas Hlth Sci Ctr San Antonio, Div Med Oncol, Dept Med, San Antonio, TX 78229 USA. [Freeman, J. W.] Canc Therapy & Res Ctr S Texas, Expt & Dev Therapeut Program, San Antonio, TX 78229 USA. [Freeman, J. W.] Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev, San Antonio, TX USA. RP Freeman, JW (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Med Oncol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freemanjw@uthscsa.edu FU VA merit award; Cancer Center Grant [NIH-RO1CA069122, NIH-P30CA054174] FX We thank Jenny Wang (University of Nebraska Medical Center, Omaha, NE) for the pSuper-shRNA-RON and Ricardo Aguiar (University of Texas Health Science Center, San Antonio, TX) for the PMMP-luciferase plasmids. We thank the University of Texas Health Science Center Animal Care and Use Committee and the Optical Imaging Facility Core of University of Texas Health Science Center (San Antonio, TX) for housing the mice and facility the animal images; and we thank the Histology and Pathology Laboratory (University of Texas Health Science Center, San Antonio, TX) for the histopathology and immunohistochemistry analysis. Grants to JWF, VA merit award, and NIH-RO1CA069122, Cancer Center Grant to CTRC, NIH-P30CA054174, supported this work. NR 50 TC 7 Z9 7 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2157-9024 J9 ONCOGENESIS JI Oncogenesis PD OCT PY 2013 VL 2 AR UNSP e76 DI 10.1038/oncsis.2013.36 PG 10 WC Oncology SC Oncology GA V36OI UT WOS:000209220600002 PM 24100611 ER PT J AU Payakachat, N Tilford, JM Kovacs, E Delahaye, J Kuhlthau, KA AF Payakachat, Nalin Tilford, J. Mick Kovacs, Erica Delahaye, Jennifer Kuhlthau, Karen A. TI Relationship between Child Health-related Quality of Life and SF6D scores for children with autism and their caregivers SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 [Payakachat, Nalin; Tilford, J. Mick] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Kovacs, Erica] Columbia Univ, Med Ctr, Div Child & Adolescent Psychiat, New York, NY 10027 USA. [Delahaye, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kuhlthau, Karen A.] Ctr Child & Adolescent Hlth Policy, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2013 VL 22 SU 1 MA 210.3 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V38QX UT WOS:000209359000095 ER PT J AU Reeve, BB Baker, J Freyer, D Jacobs, S Keller, S Kohler, RK Lyons, JC Mack, J Mowbray, C Sung, L Tomlinson, D Withycombe, J Hinds, P AF Reeve, Bryce B. Baker, Justin Freyer, David Jacobs, Shana Keller, Susan Kohler, R. Kelly Lyons, Jessica C. Mack, Jennifer Mowbray, Catriona Sung, Lillian Tomlinson, Deborah Withycombe, Janice Hinds, Pamela TI Review of self-report symptom measures in pediatric oncology research SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 [Reeve, Bryce B.; Kohler, R. Kelly; Lyons, Jessica C.] Univ N Carolina, Chapel Hill, NC 27514 USA. [Baker, Justin] St Jude Childrens Res Hosp, Memphis, TN USA. [Freyer, David] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Jacobs, Shana; Keller, Susan; Mowbray, Catriona] Childrens Natl Med Ctr, Washington, DC USA. [Mack, Jennifer] Dana Farber Canc Inst, Boston, MA USA. [Sung, Lillian; Tomlinson, Deborah] Hosp Sick Children, Toronto, ON, Canada. [Withycombe, Janice] Palmetto Hlth Chilrens Hosp, Columbia, SC USA. [Hinds, Pamela] St Judes Res Hosp, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2013 VL 22 SU 1 MA 308.3 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V38QX UT WOS:000209359000134 ER PT J AU Ullrich, CK Rodday, AM Parsons, SK AF Ullrich, Christina K. Rodday, Angie Mae Parsons, Susan K. TI Parent prognostic outlook throughout the pediatric hematopoietic stem cell transplant (HSCT) course SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 [Ullrich, Christina K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodday, Angie Mae] Tufts Med Ctr, Boston, MA USA. [Parsons, Susan K.] Tufts Med Ctr, Hlth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2013 VL 22 SU 1 MA 1049 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V38QX UT WOS:000209359000188 ER PT J AU Clark-Cutaia, MN Ren, DX Hoffman, LA Snetselaar, L Sevick, MA AF Clark-Cutaia, Maya N. Ren, Dianxu Hoffman, Leslie A. Snetselaar, Linda Sevick, Mary Ann TI Psychometric Validation of the Self-Efficacy for Restricting Dietary Salt in Hemodialysis Scale SO TOPICS IN CLINICAL NUTRITION LA English DT Article DE consistency; construct validity; convergent validity; dietary sodium intake; fluid restriction; hemodialysis; psychometrics AB The development and progression of left ventricular hypertrophy is a consequence of multiple comorbid conditions associated with end-stage renal disease and large variations in interdialytic weight gains. The literature suggests that dietary sodium restriction alone significantly reduces interdialytic weight gains. A total of 124 hemodialysis participants in an ongoing randomized control trial participated in the validation in which psychometric properties of a self-efficacy survey were a secondary analysis. We evaluated the internal consistency, construct validity, and convergent validity of the instrument. The overall Cronbach alpha was 0.93. Three factors extracted explain 67.8% of the variance of the white and African American participants. The Self-Efficacy Survey has adequate internal consistency and construct and convergent validity. Future research is needed to evaluate the stability and discriminant validity of the instrument. C1 [Clark-Cutaia, Maya N.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Ren, Dianxu] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Hoffman, Leslie A.] Univ Pittsburgh, Nursing Clin & Translat Sci, Pittsburgh, PA USA. [Snetselaar, Linda] Univ Iowa, Dept Epidemiol, Preventat Nutr Educ, Iowa City, IA USA. [Sevick, Mary Ann] US Dept Vet Affairs, VA Pittsburgh Healthcare Syst, Washington, DC USA. [Sevick, Mary Ann] Univ Pittsburgh, Ctr Res Hlth Care, Publ Hlth Clin & Translat Sci, Pittsburgh, PA USA. RP Clark-Cutaia, MN (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM Mayan@nursing.upenn.edu FU [NIH-R01-NR010135]; [NIH-K24-NR012226]; [1F31NR013410] FX This study was supported through grants from NIH-R01-NR010135, NIH-K24-NR012226 received by Mary Ann Sevick, and 1F31NR013410 received by Maya N. Clark, PhD, ACNP-BC, RN. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article . NR 38 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0883-5691 EI 1550-5146 J9 TOP CLIN NUTR JI Top. Clin. Nutr. PD OCT-DEC PY 2013 VL 28 IS 4 BP 384 EP 391 DI 10.1097/01.TIN.0000437407.76867.65 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V41NM UT WOS:000209552900008 PM 26213444 ER PT J AU Karlamangla, AS Mori, T Merkin, SS Seeman, TE Greendale, GA Binkley, N Crandall, CJ AF Karlamangla, Arun S. Mori, Takahiro Merkin, Sharon S. Seeman, Teresa E. Greendale, Gail A. Binkley, Neil Crandall, Carolyn J. TI Childhood socioeconomic status and adult femoral neck bone strength: Findings from the Mid life in the United States Study SO BONE LA English DT Article DE Bone strength; Femoral neck; Childhood socioeconomic advantage; Health behaviors ID HIP FRACTURE RISK; PHYSICAL-ACTIVITY QUESTIONNAIRE; CORONARY HEART-DISEASE; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; SOCIAL-CLASS; RANCHO-BERNARDO; ALLOSTATIC LOAD; WHITE WOMEN; ELDERLY-MEN AB Purpose: Bone acquisition in childhood impacts adult bone mass, and can be influenced by childhood socioeconomic conditions. Socioeconomic status is also associated with body weight which affects the load that bone is exposed to in a fall. We hypothesized that socioeconomic advantage in childhood is associated with greater bone strength relative to load in adulthood. Methods: Hip dual x-ray absorptiometry scans from 722 participants in the Midlife in the United States Study were used to measure femoral neck size and bone mineral density, and combined with body weight and height to create composite indices of femoral neck strength relative to load in different failure modes: compression, bending, and impact. A childhood socioeconomic advantage score was created for the same participants from parental education, self-rated financial status relative to others, and not being on welfare. Multiple linear regression was used to determine the association of childhood socioeconomic advantage with femoral neck composite strength indices, stratified by gender and race (white/non-white), and adjusted for study site, age, menopause status in women; education, and current financial advantage. Results: Childhood socioeconomic advantage was independently associated with higher indices of all three composite strength indices in white men (adjusted standardized effect sizes, 0.19 to 0.27, all p values < 0.01), but not in the other three race/gender groups. Additional adjustment for adult obesity, physical activity in different life stages, smoking, and heavy drinking over the life-course significantly attenuated the associations in white men. Conclusions: Socioeconomic disadvantage in childhood is associated with lower hip strength relative to load in white men, and these influences are dampened by healthy lifestyle choices. (C) 2013 Elsevier Inc. All rights reserved. C1 [Karlamangla, Arun S.; Merkin, Sharon S.; Seeman, Teresa E.; Greendale, Gail A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Dept Med, Los Angeles, CA 90095 USA. [Mori, Takahiro] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Binkley, Neil] Univ Wisconsin, Madison Osteoporosis Clin Ctr & Res Prog, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Crandall, Carolyn J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RP Karlamangla, AS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Dept Med, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM akarlamangla@mednet.ucla.edu FU National Institutes of Health [1R01AG033067, R01-AG-032271, P01-AG-020166]; UCLA GCRC [M01-RR000865] FX This research was supported by the National Institutes of Health grant numbers 1R01AG033067, R01-AG-032271, and P01-AG-020166. The UCLA GCRC helped support this study (UCLA GCRC grant # M01-RR000865). NR 86 TC 4 Z9 4 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 2013 VL 56 IS 2 BP 320 EP 326 DI 10.1016/j.bone.2013.06.021 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 210VX UT WOS:000323864000014 PM 23810840 ER PT J AU Gorin, Y Block, K AF Gorin, Yves Block, Karen TI Nox as a target for diabetic complications SO CLINICAL SCIENCE LA English DT Review DE diabetes; diabetic complications; hyperglycaemia; oxidative stress; Nox; reactive oxygen species; small-molecule inhibitor ID SMOOTH-MUSCLE-CELLS; ENDOTHELIAL GROWTH-FACTOR; GLYCATION END-PRODUCTS; RENIN-ANGIOTENSIN SYSTEM; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; TUBULAR EPITHELIAL-CELLS; INDUCED OXIDATIVE STRESS; ALPHA-LIPOIC ACID; DINUCLEOTIDE PHOSPHATE OXIDASE AB Oxidative stress has been linked to the pathogenesis of the major complications of diabetes in the kidney, the heart, the eye or the vasculature. NADPH oxidases of the Nox family are a major source of ROS (reactive oxygen species) and are critical mediators of redox signalling in cells from different organs afflicted by the diabetic milieu. In the present review, we provide an overview of the current knowledge related to the understanding of the role of Nox in the processes that control cell injury induced by hyperglycaemia and other predominant factors enhanced in diabetes, including the renin angiotensin system, TGF-beta (transforming growth factor-beta) and AGEs (advanced glycation end-products). These observations support a critical role for Nox homologues in diabetic complications and indicate that NADPH oxidases are an important therapeutic target. Therefore the design and development of small-molecule inhibitors that selectively block Nox oxidases appears to be a reasonable approach to prevent or retard the complications of diabetes in target organs. The bioefficacy of these agents in experimental animal models is also discussed in the present review. C1 [Gorin, Yves; Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Block, Karen] South Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 78229 USA. RP Gorin, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM gorin@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU Juvenile Diabetes Research Foundation; National Institutes of Health [RO1 DK 079996, RO1 CA 131272]; Veterans Administration FX Our own work was supported by the Juvenile Diabetes Research Foundation [Multiproject grants (to Y.G and K.B.)], the National Institutes of Health [grant number RO1 DK 079996 (to Y.G.), RO1 CA 131272 (to K.B)] and the Veterans Administration (to K.B.). NR 310 TC 47 Z9 50 U1 1 U2 50 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD OCT PY 2013 VL 125 IS 7-8 BP 361 EP 382 DI 10.1042/CS20130065 PG 22 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 210RQ UT WOS:000323852600006 PM 23767990 ER PT J AU Garland, AF Brookman-Frazee, L Gray, E AF Garland, Ann F. Brookman-Frazee, Lauren Gray, Emily TI The Role of Parent Characteristics in Community-Based Medication Treatment for Children with Disruptive Behavior Problems SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Medication treatment; Disruptive behavior; Routine care; Parent factors ID OPPOSITIONAL DEFIANT DISORDER; OFFICE-BASED PRACTICE; MENTAL-HEALTH-CARE; PSYCHOTROPIC MEDICATION; PSYCHIATRIC-DISORDERS; PRESCRIBING PRACTICES; NATIONAL TRENDS; CLINICAL-TRIAL; SERVICE USE; ADOLESCENTS AB Studies have documented increased psychoactive medication use rates among children, but little is known about what child and/or family characteristics predict medication treatment in community-based care. This study examines the role of parent characteristics in children's medication treatment, while accounting for other potential predictors. Participants included 213 children ages 4-13 with disruptive behavior problems. Medication treatment was assessed by parent report; potential predictors of medication treatment, including child characteristics and parent characteristics (e.g., education level, perceived strain and psychopathology) were assessed at service intake. Over 60 % of children used a psychoactive medication during the 16 month study period (most commonly stimulants). Parent education level and reported strain were significant predictors of children's medication treatment even when accounting for other significant predictors such as child diagnosis, age, race/ethnicity, etc. Results highlight the role that parent characteristics have in accessing community-based medication treatment for children with disruptive behavior problems. C1 [Garland, Ann F.; Brookman-Frazee, Lauren] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Garland, Ann F.; Brookman-Frazee, Lauren] Rady Childrens Hosp, Child & Adolescent Serv Res Ctr CASRC, San Diego, CA 92123 USA. [Gray, Emily] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Garland, AF (reprint author), Rady Childrens Hosp, Child & Adolescent Serv Res Ctr CASRC, 3020 Childrens Way,MC 5033, San Diego, CA 92123 USA. EM agarland@ucsd.edu FU NIMH NIH HHS [K23 MH077584, R01MH66070, P30 MH074678, K23MH077584, R01 MH066070, 1P30MH074678] NR 40 TC 3 Z9 3 U1 3 U2 18 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD OCT PY 2013 VL 49 IS 5 BP 507 EP 514 DI 10.1007/s10597-012-9514-1 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 209DZ UT WOS:000323735800002 PM 22766691 ER PT J AU Franceschini, N Haack, K Goring, HHH Voruganti, VS Laston, S Almasy, L Lee, ET Best, LG Fabsitz, RR North, KE MacCluer, JW Meigs, JB Pankow, JS Cole, SA AF Franceschini, N. Haack, K. Goering, H. H. H. Voruganti, V. S. Laston, S. Almasy, L. Lee, E. T. Best, L. G. Fabsitz, R. R. North, K. E. MacCluer, J. W. Meigs, J. B. Pankow, J. S. Cole, S. A. TI Epidemiology and genetic determinants of progressive deterioration of glycaemia in American Indians: the Strong Heart Family Study SO DIABETOLOGIA LA English DT Article DE Heritability; Impaired fasting glucose; Single nucleotide polymorphisms; Type 2 diabetes ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; NUTRITION EXAMINATION SURVEY; GENOME-WIDE ASSOCIATION; FASTING GLUCOSE; INSULIN-RESISTANCE; LIFE-STYLE; NATURAL-HISTORY; NATIONAL-HEALTH; PIMA-INDIANS AB Type 2 diabetes is a chronic, heterogeneous disease and a major risk factor for cardiovascular diseases. The underlying mechanisms leading to progression to type 2 diabetes are not fully understood and genetic tools may help to identify important pathways of glycaemic deterioration. Using prospective data on American Indians from the Strong Heart Family Study, we identified 373 individuals defined as progressors (diabetes incident cases), 566 individuals with transitory impaired fasting glucose (IFG) and 1,011 controls (normal fasting glycaemia at all visits). We estimated the heritability (h(2)) of the traits and the evidence for association with 16 known variants identified in type 2 diabetes genome-wide association studies. We noted high h(2) for diabetes progression (h(2) = 0.65 +/- 0.16, p = 2.7 x 10(-6)) but little contribution of genetic factors to transitory IFG (h(2) = 0.09 +/- 0.10, p = 0.19) for models adjusted for multiple risk factors. At least three variants (in WFS1, TSPAN8 and THADA) were nominally associated with diabetes progression in age- and sex-adjusted analyses with estimates showing the same direction of effects as reported in the discovery European ancestry studies. Our findings do not exclude these loci for diabetes susceptibility in American Indians and suggest phenotypic heterogeneity of the IFG trait, which may have implications for genetic studies when diagnosis is based on a single time-point measure. C1 [Franceschini, N.; North, K. E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Haack, K.; Goering, H. H. H.; Voruganti, V. S.; Laston, S.; Almasy, L.; MacCluer, J. W.; Meigs, J. B.; Cole, S. A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Lee, E. T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. [Best, L. G.] Missouri Breaks Ind Res, Timber Lake, SD USA. [Fabsitz, R. R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. [Meigs, J. B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Pankow, J. S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Franceschini, N (reprint author), Univ N Carolina, Dept Epidemiol, 137 E Franklin St,Suite 306 CB 8050, Chapel Hill, NC 27599 USA. EM noraf@unc.edu FU NHLBI [U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521]; NIDDK [K24 DK080140] FX The SHS is supported by NHLBI grants U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654 and U01 HL65521. J. B. Meigs is supported in part by NIDDK K24 DK080140. None of the authors have any disclosures to report. NR 49 TC 3 Z9 3 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2013 VL 56 IS 10 BP 2194 EP 2202 DI 10.1007/s00125-013-2988-8 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213MY UT WOS:000324062800013 PM 23851660 ER PT J AU Martindale, JL Noble, VE Liteplo, A AF Martindale, Jennifer L. Noble, Vicki E. Liteplo, Andrew TI Diagnosing pulmonary edema: lung ultrasound versus chest radiography SO EUROPEAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE chest radiograph; congestive heart failure; lung ultrasound; pulmonary edema ID CONGESTIVE-HEART-FAILURE; NATRIURETIC PEPTIDE; WATER; SIGN AB Background Diagnosing the underlying cause of acute dyspnea can be challenging. Lung ultrasound may help to identify pulmonary edema as a possible cause.Objective To evaluate the ability of residents to recognize pulmonary edema on lung ultrasound using chest radiographs as a comparison standard.Methods This is a prospective, blinded, observational study of a convenience sample of resident physicians in the Departments of Emergency Medicine (EM), Internal Medicine (IM), and Radiology. Residents were given a tutorial on interpreting pulmonary edema on both chest radiograph and lung ultrasound. They were then shown both ultrasounds and chest radiographs from 20 patients who had presented to the emergency department with dyspnea, 10 with a primary diagnosis of pulmonary edema, and 10 with alternative diagnoses. Cohen's values were calculated to describe the strength of the correlation between resident and gold standard interpretations.Results Participants included 20 EM, 20 IM, and 20 Radiology residents. The overall agreement with gold standard interpretation of pulmonary edema on lung ultrasound (74%, =0.51, 95% confidence interval 0.46-0.55) was superior to chest radiographs (58%, =0.25, 95% confidence interval 0.20-0.30) (P<0.0001). EM residents interpreted lung ultrasounds more accurately than IM residents. Radiology residents interpreted chest radiographs more accurately than did EM and IM residents.Conclusion Residents were able to more accurately identify pulmonary edema with lung ultrasound than with chest radiograph. Physicians with minimal exposure to lung ultrasound may be able to correctly recognize pulmonary edema on lung ultrasound. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Martindale, Jennifer L.] Kings Cty SUNY Downstate, Brooklyn, NY 11203 USA. [Noble, Vicki E.; Liteplo, Andrew] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Martindale, JL (reprint author), Kings Cty SUNY Downstate, 450 Clarkson Ave,Box 1228, Brooklyn, NY 11203 USA. EM martindale.jen@gmail.com NR 12 TC 12 Z9 15 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0969-9546 J9 EUR J EMERG MED JI Eur. J. Emerg. Med. PD OCT PY 2013 VL 20 IS 5 BP 356 EP 360 DI 10.1097/MEJ.0b013e32835c2b88 PG 5 WC Emergency Medicine SC Emergency Medicine GA 211DK UT WOS:000323884500011 PM 23263648 ER PT J AU Schaudinn, C Jaramillo, D Freire, MO Sedghizadeh, PP Nguyen, A Webster, P Costerton, JW Jiang, C AF Schaudinn, C. Jaramillo, D. Freire, M. O. Sedghizadeh, P. P. Nguyen, A. Webster, P. Costerton, J. W. Jiang, C. TI Evaluation of a nonthermal plasma needle to eliminate ex vivo biofilms in root canals of extracted human teeth SO INTERNATIONAL ENDODONTIC JOURNAL LA English DT Article DE biofilm; Endodontics; micro-CT; nonthermal plasma ID APICAL PERIODONTITIS; ENTEROCOCCUS-FAECALIS; IN-VITRO; BACTERIA; INACTIVATION; EFFICACY; IRRIGANT AB Aim To evaluate the efficacy of a nonthermal plasma (NTP) at atmospheric pressure on ex vivo biofilm in root canals of extracted teeth. Methodology Intracanal contents from three teeth with root canal infections were collected, pooled and grown in thirty-five microCT-mapped root canals of extracted and instrumented human teeth. One group of teeth was treated with NTP, another with 6% NaOCl and one set was left untreated. The intracanal contents from twenty-seven teeth (nine teeth in each group) were plated on agar and colony forming units were determined. Parametric test of one-way analysis of variance (ANOVA) was used to analyse statistical significance. The remaining teeth were cut open, stained with LIVE/DEAD (R) and examined with confocal laser scanning microscopy. Results The untreated root canals were covered with biofilm of varying thickness. Treatment with nonthermal plasma decreased the number of viable bacteria in biofilms by one order of magnitude, whilst the NaOCl control achieved a reduction of more than four magnitudes. Both the NTP and the NaOCl treatment results were significantly different from the negative control (P < 0.05). Conclusion The nonthermal plasma displayed antimicrobial activity against endodontic biofilms in root canals, but was not as effective as the use of 6% NaOCl. C1 [Schaudinn, C.] Robert Koch Inst, Berlin, Germany. [Schaudinn, C.; Webster, P.] House Ear Res Inst, Los Angeles, CA 90034 USA. [Jaramillo, D.] Loma Linda Univ, Sch Dent, Loma Linda, CA 92350 USA. [Freire, M. O.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. [Sedghizadeh, P. P.; Nguyen, A.] Univ So Calif, Herman Ostrow Sch Dent, Los Angeles, CA 90089 USA. [Costerton, J. W.] Allegheny Singer Res Inst, Pittsburgh, PA 15212 USA. [Jiang, C.] Univ So Calif, Viterbi Sch Engn, Los Angeles, CA 90089 USA. RP Jiang, C (reprint author), Univ So Calif, Dept Elect Engn Electrophys, Viterbi Sch Engn, Los Angeles, CA 90089 USA. EM chunqi@usc.edu OI Sedghizadeh, Parish/0000-0003-4190-0497; Freire, Marcelo/0000-0003-4906-7698 FU National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health [R21-DE020167-01A1] FX The work is supported by a research grant (R21-DE020167-01A1) from the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health. We affirm that there is no potential conflict of interest and no financial affiliation or involvement with any commercial organization with direct interest in the subject or materials of the presented work. NR 23 TC 9 Z9 9 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0143-2885 J9 INT ENDOD J JI Int. Endod. J. PD OCT PY 2013 VL 46 IS 10 BP 930 EP 937 DI 10.1111/iej.12083 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 211DP UT WOS:000323885300006 PM 23480318 ER PT J AU Weintraub, D Duda, JE Carlson, K Luo, P Sagher, O Stern, M Follett, KA Reda, D Weaver, FM AF Weintraub, Daniel Duda, John E. Carlson, Kimberly Luo, Ping Sagher, Oren Stern, Matthew Follett, Kenneth A. Reda, Domenic Weaver, Frances M. CA CSP 468 Study Grp TI Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE PARKINSON'S DISEASE; BEHAVIOURAL DISORDER; SURGERY ID DEEP-BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; HEALTH SURVEY SF-36; MOVEMENT-DISORDERS; MEDICAL THERAPY; DEPRESSION; OUTCOMES; MOOD; RISK AB Background The risk of suicide behaviours post-deep brain stimulation (DBS) surgery in Parkinson's disease (PD) remains controversial. We assessed if suicide ideation and behaviours are more common in PD patients (1) randomised to DBS surgery versus best medical therapy (BMT); and (2) randomised to subthalamic nucleus (STN) versus globus pallidus interna (GPi) DBS surgery. Methods In Phase 1 of the Veterans Affairs CSP 468 study, 255 PD patients were randomised to DBS surgery (n=121) or 6months of BMT (n=134). For Phase 2, a total of 299 patients were randomised to STN (n=147) or GPi (n=152) DBS surgery. Patients were assessed serially with the Unified Parkinson's Disease Rating Scale Part I depression item, which queries for suicide ideation; additionally, both suicide behaviour adverse event data and proxy symptoms of increased suicide risk from the Parkinson's Disease Questionnaire (PDQ-39) and the Short Form Health Survey (SF-36) were collected. Results In Phase 1, no suicide behaviours were reported, and new-onset suicide ideation was rare (1.9% for DBS vs 0.9% for BMT; Fisher's exact p=0.61). Proxy symptoms of relevance to suicide ideation were similar in the two groups. Rates of suicide ideation at 6months were similar for patients randomised to STN versus GPi DBS (1.5% vs 0.7%; Fisher's exact p=0.61), but several proxy symptoms were worse in the STN group. Conclusions Results from the randomised, controlled phase of a DBS surgery study in PD patients do not support a direct association between DBS surgery and an increased risk for suicide ideation and behaviours. C1 [Weintraub, Daniel; Duda, John E.; Stern, Matthew] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Philadelphia, PA USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel; Duda, John E.; Stern, Matthew] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Carlson, Kimberly; Luo, Ping; Reda, Domenic] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Vet Affairs Cooperat Studies, Program Coordinating Ctr, Hines, IL 60141 USA. [Sagher, Oren] Univ Michigan, Sch Med, Dept Neurosurg, Ann Arbor, MI USA. [Follett, Kenneth A.] Univ Nebraska, Med Ctr, Omaha VA Med Ctr, Omaha, NE USA. [Follett, Kenneth A.] Univ Nebraska, Med Ctr, Div Neurosurg, Omaha, NE USA. [Weaver, Frances M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hlth Serv Res Ctr, Hines, IL 60141 USA. [Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Dept Med, Chicago, IL 60611 USA. RP Weintraub, D (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia VA Med Ctr, 3615 Chestnut St 330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Cooperative Studies Programme of the Department of Veterans Affairs Office of Research and Development; National Institute of Neurological Disorders and Stroke; Medtronic Neuromodulation [NCT00056563, NCT 01076452.] FX The Cooperative Studies Programme of the Department of Veterans Affairs Office of Research and Development, the National Institute of Neurological Disorders and Stroke, and Medtronic Neuromodulation provided financial support for this study NCT00056563 and NCT 01076452. NR 30 TC 28 Z9 28 U1 0 U2 19 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD OCT PY 2013 VL 84 IS 10 BP 1113 EP 1118 DI 10.1136/jnnp-2012-304396 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 209SH UT WOS:000323779800013 PM 23667214 ER PT J AU Kim, JY Kim, N Zheng, Z Lee, JE Yenari, MA AF Kim, Jong Youl Kim, Nuri Zheng, Zhen Lee, Jong Eun Yenari, Midori A. TI The 70 kDa heat shock protein protects against experimental traumatic brain injury SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Brain injury; Heat shock protein; Cerebral hemorrhage ID OXYGEN-GLUCOSE DEPRIVATION; MATRIX METALLOPROTEINASES; EXPERIMENTAL STROKE; CEREBRAL-ISCHEMIA; INFLAMMATORY RESPONSE; BARRIER DISRUPTION; STRESS-RESPONSE; OVEREXPRESSION; BLOOD; MATRIX-METALLOPROTEINASE-9 AB Traumatic brain injury (TBI) causes disruption of the blood brain barrier (BBB) leading to hemorrhage which can complicate an already catastrophic illness. Matrix metalloproteinases (MMPs) involved in the breakdown of the extracellular matrix may lead to brain hemorrhage. We explore the contribution of the 70 kDa heat shock protein (Hsp70) to outcome and brain hemorrhage in a model of TBI. Male, wildtype (Wt), Hsp70 knockout (Ko) and transgenic (Tg) mice were subjected to TBI using controlled cortical impact (CCI). Motor function, brain hemorrhage and lesion size were assessed at 3, 7 and 14 days. Brains were evaluated for the effects of Hsp70 on MMPs. In Hsp70 Tg mice, CCI led to smaller brain lesions, decreased hemorrhage and reduced expression and activation of MMPs compared to Wt. CCI also significantly decreased right-biased swings and corner turns in the Hsp70 Tg mice. Conversely, Hsp70 Ko mice had significantly increased lesion size, worsened brain hemorrhage and increased expression and activation of MMPs with worsened behavioral outcomes compared to Wt. Hsp70 is protective in experimental TBI. To our knowledge, this is the direct demonstration of brain protection by Hsp70 in a TBI model. Our data demonstrate a new mechanism linking TBI-induced hemorrhage and neuronal injury to the suppression of MMPs by Hsp70, and support the development of Hsp70 enhancing strategies for the treatment of TBI. Published by Elsevier Inc. C1 [Kim, Jong Youl; Kim, Nuri; Zheng, Zhen; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Kim, Jong Youl; Kim, Nuri; Zheng, Zhen; Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Lee, Jong Eun] Yonsei Univ, Coll Med, Dept Anat, Seoul, South Korea. [Lee, Jong Eun] Yonsei Univ, Coll Med, BK Project Med Sci 21, Seoul, South Korea. RP Yenari, MA (reprint author), VAMC 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu OI Lee, Jong Eun/0000-0001-6203-7413 FU National Institutes of Health [NS40516]; Veteran's Merit Award; American Heart Association Western States Affiliate Postdoctoral Fellowship [13POST14810019]; NRF of KOREA; Ministry of Education, Science and Technology [2012-0005827] FX This work was supported by grants from the National Institutes of Health (NS40516) and the Veteran's Merit Award to MY, an American Heart Association Western States Affiliate Postdoctoral Fellowship (13POST14810019) to JYK and Basic Science Research Program through the NRF of KOREA funded by the Ministry of Education, Science and Technology (2012-0005827) to JEL. Grants to MY and JYK were administered by the Northern California Institute for Research and Education, and supported by resources of the Veterans Affairs Medical Center, San Francisco, California. The authors wish to thank Dr. Linda Noble-Haeusslein for helpful discussion and advice. NR 56 TC 18 Z9 19 U1 0 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2013 VL 58 BP 289 EP 295 DI 10.1016/j.nbd.2013.06.012 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 207GC UT WOS:000323585900033 PM 23816752 ER PT J AU Potenza, AS Phelan, EA Cernea, CR Slough, CM Kamani, DV Darr, A Zurakowski, D Randolph, GW AF Potenza, Andre S. Phelan, Eimear A. Cernea, Claudio R. Slough, Cristian M. Kamani, Dipti V. Darr, Ashlie Zurakowski, David Randolph, Gregory W. TI Normative Intra-operative Electrophysiologic Waveform Analysis of Superior Laryngeal Nerve External Branch and Recurrent Laryngeal Nerve in Patients Undergoing Thyroid Surgery SO WORLD JOURNAL OF SURGERY LA English DT Article ID IDENTIFICATION; INNERVATION; PARALYSIS; MUSCLE; ELECTROMYOGRAPHY AB Injury to the external branch of the superior laryngeal nerve (EBSLN) can occur during superior pole dissection in thyroid surgery; the EBSLN injury rate is reported as high as 28 % (Cernea et al., Head Neck 14:380-383, 1992). Injury to the EBSLN leads to variable symptoms that may be overlooked, but that can be significant, especially to professional speakers and singers. Intraoperative nerve monitoring (IONM) is employed widely to aid in nerve identification. We report on normative electroneuromyography (EMG) data on EBSLN-IONM and cricothyroid muscle (CTM) twitch response during stimulation as an aid to EBSLN identification. A prospective study of the SLN and the recurrent laryngeal nerve (RLN) IONM data in 72 consecutive thyroid surgeries was carried out. All patients underwent preoperative and postoperative laryngeal exams, and patients with abnormal preoperative laryngeal function were excluded. Normative EMG data and CTM twitch response during EBSLN stimulation were recorded and analyzed. Stimulation of the EBSLN resulted in a positive CTM twitch response in 100 %, whereas EMG response was recordable in 80 %. Electromyographic amplitude was similar to 1/3 of ipsilateral RLN amplitude and did not change through the case with multiple stimulations. Stimulation of the EBSLN was similar for men and women and at 1 and 2 mA stimulation levels. Intraoperative nerve monitoring of the EBSLN aids in EBSLN identification and provides electroneuromyographic information in 80 % of cases. The laryngeal head of the sternothyroid muscle is a useful landmark to locate EBSLN. C1 [Potenza, Andre S.; Phelan, Eimear A.; Slough, Cristian M.; Kamani, Dipti V.; Darr, Ashlie; Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Thyroid & Parathyroid Surg,Dept Otol & Laryng, Boston, MA 02114 USA. [Cernea, Claudio R.] Univ Sao Paulo, Sch Med, Dept Head & Neck Surg, Sao Paulo, Brazil. [Zurakowski, David] Harvard Univ, Sch Med, Childrens Hosp, Dept Anesthesiol, Boston, MA USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp, Boston, MA 02115 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Endocrine Surg Serv, Boston, MA 02114 USA. RP Randolph, GW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Thyroid & Parathyroid Surg,Dept Otol & Laryng, 243 Charles St, Boston, MA 02114 USA. EM dipti_kamani@meei.harvard.edu; gregory_randolph@meei.harvard.edu RI Cernea, Claudio/F-5610-2016 NR 25 TC 18 Z9 18 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD OCT PY 2013 VL 37 IS 10 BP 2336 EP 2342 DI 10.1007/s00268-013-2148-9 PG 7 WC Surgery SC Surgery GA 208IU UT WOS:000323672300013 PM 23838931 ER PT J AU Orthopoulos, G Sideris, A Velmahos, E Troulis, M AF Orthopoulos, George Sideris, Antonios Velmahos, Elpida Troulis, Maria TI Gunshot Wounds to the Face: Emergency Interventions and Outcomes SO WORLD JOURNAL OF SURGERY LA English DT Article ID MANAGEMENT AB Gunshot wounds to the face (GSWF) may produce life-threatening injuries. Our objective is to describe outcomes of and factors related to interventions for urgent airway control (UAC) and urgent bleeding control (UBC) as well as to analyze complications associated with GSWF. This was a retrospective study of 155 GSWF patients who were admitted to two Level 1 academic trauma centers over an 11-year period. Demographic details, injuries sustained, interventions performed, and timing of the interventions were recorded. Morbidity and mortality data were evaluated. Overall, 115 (74 %) patients suffered isolated GSWF, and none died. Of the 90 (58 %) patients requiring UAC, only three had a cricothyroidotomy. Of the 41 (26 %) patients requiring UBC, only four had angiographic embolization. Intraoral involvement and extrafacial injuries were associated with both UAC and UBC. Overall, 75 patients (48 %) required operations on the bones, eyes, or both. Complications developed in 14 and were treated successfully. UAC and UBC are required frequently after GSWF and are associated with intraoral involvement and injuries beyond the face. Simple methods, such as orotracheal intubation and packing, are typically sufficient for successful management. About half of the patients need further surgery, with infrequent morbidity. C1 [Orthopoulos, George] Boston Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02118 USA. [Sideris, Antonios; Velmahos, Elpida] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Sideris, Antonios; Velmahos, Elpida; Troulis, Maria] Harvard Univ, Sch Med, Boston, MA USA. [Troulis, Maria] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Orthopoulos, G (reprint author), Boston Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, 820 Harisson Ave,FGH 4, Boston, MA 02118 USA. EM george.orthopoulos@bmc.org NR 10 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD OCT PY 2013 VL 37 IS 10 BP 2348 EP 2352 DI 10.1007/s00268-013-2139-x PG 5 WC Surgery SC Surgery GA 208IU UT WOS:000323672300015 PM 23811793 ER PT J AU Manrique, P Freire, MO Chen, C Zadeh, HH Young, M Suci, P AF Manrique, P. Freire, M. O. Chen, C. Zadeh, H. H. Young, M. Suci, P. TI Perturbation of the indigenous rat oral microbiome by ciprofloxacin dosing SO MOLECULAR ORAL MICROBIOLOGY LA English DT Article DE ciprofloxacin; microbiome; oral; periodontitis; rat ID PERIODONTAL-DISEASE; ROTHIA DENTOCARIOSA; AGGREGATIBACTER-ACTINOMYCETEMCOMITANS; STAPHYLOCOCCUS-AUREUS; IMMUNE-RESPONSE; BONE-RESORPTION; BACTERIA; MICROFLORA; BIOFILM; IDENTIFICATION AB Mucosal surfaces such as the gut, vagina and oral cavity are colonized by microbiota that are an integral component of the healthy ecosystem. Recent molecular techniques make it feasible to correlate antimicrobial dosing levels with changes in microbiome composition. The objective of this study was to characterize the rat oral plaque microbiome composition at doses of ciprofloxacin that were considerably above and below nominal in vitro minimal inhibitory concentrations of a variety of gram-positive oral commensal bacteria. We exposed the oral cavities of rats to relatively low (0.1 lg ml(-1)) and high (20 lg ml(-1)) doses of ciprofloxacin in the drinking water over a 3-day period. Plaque microbiota were characterized using 454 pyrosequencing. The rat indigenous community was dominated by the genera Rothia (74.4%) and Streptococcus (4.7%). Dosing at 0.1 lg ml-1 was associated with changes in Rothia and Streptococcus species that were not significant, whereas dosing at 20 lg ml(-1) caused a pronounced (significant) reduction in the relative abundance of the Streptococcus genus. Taxonomic independent analysis indicated that the perturbation in the overall community structure attributed to dosing with ciprofloxacin at either the low or high dose was relatively low. The results suggest that it is feasible to use an anti-microbial dosing regimen to selectively target a specific subset of a mucosal microbiome for elimination with minimal perturbation of the entire community. C1 [Manrique, P.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. [Freire, M. O.] Forsyth Inst, Cambridge, MA USA. [Chen, C.; Zadeh, H. H.] Univ So Calif, Herman Ostrow Sch Dent, Los Angeles, CA USA. [Young, M.; Suci, P.] Montana State Univ, Dept Plant Sci, Bozeman, MT 59717 USA. RP Suci, P (reprint author), Montana State Univ, Dept Plant Sci, Bozeman, MT 59717 USA. EM peter_s@erc.montana.edu OI Freire, Marcelo/0000-0003-4906-7698 FU National Institutes of Health [1R21DE019237-01A1] FX This work was supported by National Institutes of Health grant 1R21DE019237-01A1 to MY. NR 54 TC 2 Z9 2 U1 0 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2041-1006 J9 MOL ORAL MICROBIOL JI Mol. Oral Microbiol. PD OCT PY 2013 VL 28 IS 5 BP 404 EP 414 DI 10.1111/omi.12033 PG 11 WC Dentistry, Oral Surgery & Medicine; Microbiology SC Dentistry, Oral Surgery & Medicine; Microbiology GA 204OT UT WOS:000323377800007 PM 23844936 ER PT J AU Zhu, BL Smith, J Yarmush, ML Nahmias, Y Kirby, BJ Murthy, SK AF Zhu, Beili Smith, James Yarmush, Martin L. Nahmias, Yaakov Kirby, Brian J. Murthy, Shashi K. TI Microfluidic Enrichment of Mouse Epidermal Stem Cells and Validation of Stem Cell Proliferation In Vitro SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID HAIR FOLLICLE BULGE; SEPARATION; SKIN; CAPTURE; MULTIPOTENCY; NICHE AB Bulge stem cells reside in the lowest permanent portion of hair follicles and are responsible for the renewal of these follicles along with the repair of the epidermis during wound healing. These cells are identified by surface expression of CD34 and the alpha 6-integrin. When CD34 and alpha 6 double-positive cells are isolated and implanted into murine skin, they give rise to epidermis and hair follicle structures. The current gold standard for isolation of these stem cells is fluorescence-activated cell sorting (FACS) based on cell surface markers. Here, we describe an alternative method for CD34 bulge stem cell isolation: a microfluidic platform that captures stem cells based on cell surface markers. This method is relatively fast, requiring 30 min of time from direct introduction of murine skin tissue digestate into a two-stage microfluidic device to one-pass elution of CD34(+) enriched cells with a purity of 55.8%+/- 5.1%. The recovered cells remain viable and formed colonies with characteristic morphologies. When grown in culture, enriched cells contain a larger alpha 6(+) population than un-enriched cells. C1 [Zhu, Beili; Murthy, Shashi K.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Dept Chem Engn, Boston, MA 02115 USA. [Smith, James; Kirby, Brian J.] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. [Yarmush, Martin L.; Nahmias, Yaakov] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA USA. [Yarmush, Martin L.; Nahmias, Yaakov] Shriners Hosp Children, Boston, MA USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. [Kirby, Brian J.] Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY USA. RP Murthy, SK (reprint author), Northeastern Univ, Barnett Inst Chem & Biol Anal, Dept Chem Engn, 360 Huntington Ave,342 Snell Engn, Boston, MA 02115 USA. EM s.murthy@neu.edu RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU National Institutes of Health [R01-EB009327] FX Funding was provided by National Institutes of Health under grant R01-EB009327. NR 32 TC 11 Z9 11 U1 1 U2 28 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD OCT PY 2013 VL 19 IS 10 BP 765 EP 773 DI 10.1089/ten.tec.2012.0638 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 203SX UT WOS:000323314700003 PM 23394261 ER PT J AU Shen, Z Chen, L Yang, XJ Zhao, Y Pier, E Zhang, X Yang, XC Xiong, Y AF Shen, Zhu Chen, Ling Yang, Xiaojun Zhao, Yun Pier, Eric Zhang, Xia Yang, Xichuan Xiong, Ya TI Downregulation of Ezh2 methyltransferase by FOXP3: New insight of FOXP3 into chromatin remodeling? SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE FOXP3; Ezh2; Praja1; Transcription; Ubiquitination ID GROUP PROTEIN EZH2; BREAST-CANCER; T-CELLS; TARGET GENES; DNA-DAMAGE; STEM-CELLS; C-MYC; EXPRESSION; ROLES; HYPERMETHYLATION AB Transcription factor FOXP3 (forkhead box P3) is found initially as a key regulator in regulatoiy T cells. Recently its expression has been demonstrated in some non-lymphoid normal and cancerous cells. Now FOXP3 has been proven to regulate cancer-related genes, especially suppressor genes in breast cancer. But the mechanisms by which FOXP3 regulates suppressor genes are not fully determined. In this study, we found the inverse correlation between FOXP3 and Ezh2, an enzyme for histone H3K27 trimethylation (H3K27me3) and a central epigenetic regulator in cancer. The overexpression of FOXP3 weakened Ezh2's enhancement on the mammosphere formation, cell proliferation, directional migration, and colony forming ability of T47D cells. We demonstrated that FOXP3 could downregulate Ezh2 protein level and this depended on not only the FOXP3 expression amount, but also the nuclear localization of FOXP3. More importantly, we demonstrated FOXP3 accelerated Ezh2 protein degradation through the polyubiquitination-proteasome pathway by enhancing the transcription of E3 ligase Praja1 directly. These results provided a new mechanism for FOXP3 in histone modifications as an Ezh2 suppressor and supported new evidence for FOXP3 as a tumor suppressor in breast cancer. 2013 Elsevier B.V. All rights reserved. C1 [Shen, Zhu; Yang, Xichuan; Xiong, Ya] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Chen, Ling] Third Mil Med Univ, Daping Hosp, Dept Dermatol, Chongqing 400042, Peoples R China. [Yang, Xiaojun; Zhang, Xia] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. [Yang, Xiaojun; Zhang, Xia] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China. [Yang, Xiaojun; Zhang, Xia] Minist Educ China, Key Lab Tumor Immunopathol, Chongqing 400038, Peoples R China. [Zhao, Yun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pier, Eric] Tufts Univ, Sch Med, Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Shen, Z (reprint author), Third Mil Med Univ, Southwest Hosp, Dept Dermatol, 30 Gaotanyan Main St, Chongqing 400038, Peoples R China. EM zhushencq@gmail.com RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 FU National Natural Science Foundation of China [30801013, 81072502]; Natural Science Foundation Project of CQ CSTC [CSTC 2009BA5010]; project for the Medical Science Development of PLA [CWS12J027] FX This work was supported by the National Natural Science Foundation of China (No. 30801013, Ling Chen; and No. 81072502, Zhu Shen), the Natural Science Foundation Project of CQ CSTC (No. CSTC 2009BA5010, Zhu Shen), and the project for the Medical Science Development of PLA (No. CWS12J027, Ling Chen). NR 45 TC 5 Z9 6 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT PY 2013 VL 1833 IS 10 BP 2190 EP 2200 DI 10.1016/j.bbamcr.2013.05.014 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 197OA UT WOS:000322859300009 PM 23688634 ER PT J AU Mallampalli, RK Kaercher, L Snavely, C Pulijala, R Chen, BB Coon, T Zhao, J Agassandian, M AF Mallampalli, Rama K. Kaercher, Leah Snavely, Courtney Pulijala, Roopa Chen, Bill B. Coon, Tiffany Zhao, Jing Agassandian, Marianna TI Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase I SO CELLULAR SIGNALLING LA English DT Article DE F-box protein; CaMKI; Calcium signaling; Proteasome degradation; p27(kip1); cdk4/cyclin D1; PKB/AKT ID CELL-CYCLE ARREST; ACTIVATED PROTEIN-KINASE; NUCLEAR EXPORT SIGNAL; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; DEPENDENT PHOSPHORYLATION; P27(KIP1) PHOSPHORYLATION; SUBCELLULAR-LOCALIZATION; CYTOPLASMIC LOCALIZATION; P27 STABILIZATION AB Cell cycle progression through its regulatory control by changes in intracellular Ca2+ levels at the Gl/S transition mediates cellular proliferation and viability. Ca2+/CaM-dependent kinase 1 (CaMKI) appears critical in regulating the assembly of the cyclin D1 /cdk4 complex essential for G1 progression, but how this occurs is unknown. Cyclin D1/cdk4 assembly in the early G1 phase is also regulated via binding to p27. Here, we show that a ubiquitin E3 ligase component, F-box protein Fbxl12, mediates CaMKI degradation via a proteasome-directed pathway leading to disruption of cyclin D1/cdk4 complex assembly and resultant G1 arrest in lung epithelia. We also demonstrate that i) CaMKI phosphorylates p27 at Thr(157) and Thr(198) in human cells and at Thr(170) and Thr(197) in mouse cells to modulate its subcellular localization; ii) Fbxl12-induced CaMKI degradation attenuates p27 phosphorylation at these sites in early G1 and iii) activation of CaMIG during G1 transition followed by p27 phosphorylation appears to be upstream to other p27 phosphorylation events, an effect abrogated by Fbxl12 overexpression. Lastly, known inducers of G1 arrest significantly increase Fbxl12 levels in cells. Thus, Fbxl12 may be a previously uncharacterized, functional growth inhibitor regulating cell cycle progression that might be used for mechanism-based therapy. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved. C1 [Mallampalli, Rama K.; Kaercher, Leah; Snavely, Courtney; Pulijala, Roopa; Chen, Bill B.; Coon, Tiffany; Zhao, Jing; Agassandian, Marianna] 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, Pittsburgh, PA 15213 USA. RP Agassandian, M (reprint author), Univ Pittsburgh, BST 1,W1200-5B,200 Lothrop St, Pittsburgh, PA 15213 USA. EM agassandianm@upmc.edu FU US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174, HL116472]; American Heart Association (AHA) [12SDG9050005] FX We greatly appreciate Cheryl Lyn Walker, Director of Institute of Biosciences & Technology Center for Translational Cancer Research of University of Texas's kind gifts of p27WT, p27T170A, p27T197A and p27T170A/197A plasmids. 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 the National Institutes of Health R01 grants HL096376, HL097376 and HL098174 (to R.K.M.), and HL116472 (to B.B.C.) and from the American Heart Association (AHA) awards 12SDG9050005 (J.Z.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 74 TC 5 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 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD OCT PY 2013 VL 25 IS 10 BP 2047 EP 2059 DI 10.1016/j.cellsig.2013.05.012 PG 13 WC Cell Biology SC Cell Biology GA 198SX UT WOS:000322943700012 PM 23707388 ER PT J AU Dodson, M Darley-Usmar, V Zhang, JH AF Dodson, Matthew Darley-Usmar, Victor Zhang, Jianhua TI Cellular metabolic and autophagic pathways: Traffic control by redox signaling SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE Autophagy; Mitophagy; Oxidative stress; Redox signaling; Cellular bioenergetics; Mitochondria; Glucose; Glycolysis; Glutathione; Aging; Cardiovascular disease; Neurodegeneration; Diabetes; Free radicals ID MITOCHONDRIA-TARGETED ANTIOXIDANT; ENDOPLASMIC-RETICULUM STRESS; ELECTRON-TRANSPORT-CHAIN; NEGATIVELY REGULATES AUTOPHAGY; CHAPERONE-MEDIATED AUTOPHAGY; LIPID-PEROXIDATION PRODUCTS; PENTOSE-PHOSPHATE PATHWAY; EMBRYONIC STEM-CELLS; OXIDATIVE STRESS; ENDOTHELIAL-CELLS AB It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function. (C) 2013 Elsevier Inc. All rights reserved. C1 [Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35233 USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, 901 19th St South,BMR2 534, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU VA merit award; NIH [ES10167, AA13395, DK 75865]; [NIHR01-NS064090] FX The authors acknowledge funding from the following sources: Dr. Jianhua Zhang was supported by NIHR01-NS064090 and a VA merit award. Dr. Victor Darley-Usmar was supported by NIH Grants ES10167, AA13395, and DK 75865. NR 209 TC 98 Z9 107 U1 13 U2 151 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 OCT PY 2013 VL 63 SI SI BP 207 EP 221 DI 10.1016/j.freeradbiomed.2013.05.014 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 200TV UT WOS:000323094700019 PM 23702245 ER PT J AU Sonis, ST Antin, JH Tedaldi, MW Alterovitz, G AF Sonis, S. T. Antin, J. H. Tedaldi, M. W. Alterovitz, G. TI SNP-based Bayesian networks can predict oral mucositis risk in autologous stem cell transplant recipients SO ORAL DISEASES LA English DT Article DE oral mucositis; risk prediction; SNP; stem cell transplant ID GENOME; ASSOCIATION; TOXICITY; OUTCOMES; THERAPY; CANCERS; DNA AB Objective Approximately 40% of patients receiving conditioning chemotherapy prior to autologous hematopoietic stem cell transplants (aHSCT) develop severe oral mucositis (SOM). Aside from disabling pain, ulcerative lesions associated with SOM predispose to poor health and economic outcomes. Our objective was to develop a probabilistic graphical model in which a cluster of single-nucleotide polymorphisms (SNPs) derived from salivary DNA could be used as a tool to predict SOM risk. Methods Salivary DNA was extracted from 153 HSCT patients and applied to Illumina BeadChips. Using sequential data analysis, we filtered extraneous SNPs, selected loci, and identified a predictive SNP network for OM risk. We then tested the predictive validity of the network using SNP array outputs from an independent HSCT cohort. Results We identified an 82-SNP Bayesian network (BN) that was related to SOM risk with a 10-fold cross-validation accuracy of 99.3% and an area under the ROC curve of 99.7%. Using samples from a small independent patient cohort (n=16), we demonstrated the network's predictive validity with an accuracy of 81.2% in the absence of any false positives. Conclusions Our results suggest that SNP-based BN developed from saliva-sourced DNA can predict SOM risk in patients prior to aHSCT. C1 [Sonis, S. T.; Alterovitz, G.] Inform Genom, Boston, MA USA. [Sonis, S. T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Antin, J. H.; Tedaldi, M. W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Alterovitz, G.] Childrens Med Ctr, Boston, MA USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org FU SOBI Pharmaceuticals; Biomodels LLC; InformGenomics FX This work was supported by SOBI Pharmaceuticals, Biomodels LLC, and InformGenomics. NR 25 TC 14 Z9 14 U1 2 U2 55 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD OCT PY 2013 VL 19 IS 7 BP 721 EP 727 DI 10.1111/odi.12146 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 202JK UT WOS:000323210600011 PM 23809011 ER PT J AU Malogolowkin, MH Krailo, M Marina, N Olson, T Frazier, AL AF Malogolowkin, Marcio H. Krailo, Mark Marina, Neyssa Olson, Thomas Frazier, A. Lindsay TI Pilot study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high risk germ cell tumors: A report of the children's oncology group (COG) SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cyclophosphamide; germ cell tumors; maximum tolerated doses ID CHEMOTHERAPY AB Background To establish the maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide with cisplatin, etoposide, and bleomycin (C-PEB) in children with high-risk malignant germ cell tumors (HR-MGCT). Procedure Eligibility criteria included untreated patients21 years of age with stage III/IV extragonadal, extra cranial MGCT. Patients received four cycles (repeated every 3 weeks) of cisplatin (20mg/m(2)/dayx5 days), etoposide (100mg/m(2)/dayx5 days), and bleomycin (15mg/m(2) on Day 1) with escalating doses of cyclophosphamide on Day 1, assigned at the time of enrollment (1.2, 1.8, or 2.4g/m(2)). Patients with complete response had therapy discontinued. Patients with residual disease underwent second-look surgery, those with pathologic evidence of residual MGCT or whose markers had not normalized received two more cycles. All other patients had protocol therapy stopped. Results Nineteen patients were enrolled between July 2004 and August 2007. Three patients were non-evaluable. Sixteen patients completed four cycles. Eleven had complete response, one had progressive disease and four had partial response. All four with partial response underwent second look surgery followed by two more cycles. Only one patient, on dose 1.8g/m(2), experienced dose-limiting toxicity (DLT) during the first cycle of therapy (grade 3 hyperglycemia). The 4-year EFS and OS (+/- standard deviation) were 74 +/- 7% and 89 +/- 10%, respectively. Conclusion The addition of cyclophosphamide to the standard PEB regimen (cisplatin, etoposide, and bleomycin) is feasible and well-tolerated at all dose levels used on this study. Pediatr Blood Cancer 2013;60:1602-1605. (c) 2013 Wiley Periodicals, Inc. C1 [Malogolowkin, Marcio H.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Krailo, Mark] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Marina, Neyssa] Stanford Univ, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [Olson, Thomas] Emory Univ, Atlanta, GA 30322 USA. [Olson, Thomas] Childrens Healthcare Atlanta, Atlanta, GA USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Malogolowkin, MH (reprint author), Med Coll Wisconsin, Div Hematol Oncol Bone Marrow Transplant, Childrens Hosp Wisconsin, MFRC 3018,8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM mmalogol@mcw.edu FU COG Chair's Grant [U10 CA98543-08]; Statistics and Data Center [U10 CA98413-08] FX Grant sponsor: COG Chair's Grant; Grant number: U10 CA98543-08; Grant sponsor: Statistics and Data Center; Grant number: U10 CA98413-08 NR 10 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2013 VL 60 IS 10 BP 1602 EP 1605 DI 10.1002/pbc.24601 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 197XG UT WOS:000322885200016 PM 23703725 ER PT J AU Robison, NJ Prabhu, SP Sun, PL Chi, SN Kieran, MW Manley, PE Cohen, LE Goumnerova, L Smith, ER Scott, RM London, WB Ullrich, NJ AF Robison, Nathan J. Prabhu, Sanjay P. Sun, Pengling Chi, Susan N. Kieran, Mark W. Manley, Peter E. Cohen, Laurie E. Goumnerova, Liliana Smith, Edward R. Scott, R. Michael London, Wendy B. Ullrich, Nicole J. TI Predictors of neoplastic disease in children with isolated pituitary stalk thickening SO PEDIATRIC BLOOD & CANCER LA English DT Article DE diabetes insipidus; germ cell tumor; germinoma; infundibulum; Langerhans cell histiocytosis; pituitary stalk thickening ID CENTRAL DIABETES-INSIPIDUS; LANGERHANS CELL HISTIOCYTOSIS; LYMPHOCYTIC INFUNDIBULONEUROHYPOPHYSITIS; INTRACRANIAL GERMINOMA; PANHYPOPITUITARISM; HYPOPHYSITIS; ADOLESCENTS AB Background The significance of pituitary stalk thickening (PST) on magnetic resonance imaging (MRI) is often unclear. We evaluated presenting symptoms, MRI findings, clinical course, and outcome predictors of patients with PST. Procedure We used a computerized search of the medical record from 1995 to 2008 to identify patients with PST without pituitary mass on MRI. Baseline and follow-up MRIs were reviewed in a blinded fashion. Relevant clinical data were abstracted. Results 69 patients with reported PST and adequate imaging for review were identified; 42 met study criteria. Median age at first abnormal MRI was 13.6 years (range: 0.8-19.7); 43% were male. Median follow-up was 3.4 years (range 0-12.8). Patients with diabetes insipidus (DI) were significantly more likely to have a neoplastic process than those without (P=0.0008). Of 16 patients with DI, 8 (50%) had a neoplastic process, including germ cell tumor (n=4), Langerhans cell histiocytosis (n=3), and lymphoma (n=1). Among patients with DI, 7 (44%) also developed anterior pituitary hormone dysfunction (APD), either at presentation or on pre-biopsy follow-up, including 6/8 patients with stalk neoplasm and only 1/8 patients with non-neoplastic PST (P=0.04). Twenty-six patients presented without DI; none was found to have neoplasm of the stalk except one patient with craniopharyngioma. Progression of PST on follow-up imaging was significantly associated with a subsequent neoplastic diagnosis (P=0.04). Conclusion Patients with PST without DI are unlikely to have a neoplastic process. Among patients with DI, APD or progressive stalk increase over time are predictive of neoplasia. Pediatr Blood Cancer 2013;60:1630-1635. (c) 2013 Wiley Periodicals, Inc. C1 [Robison, Nathan J.; Sun, Pengling; Chi, Susan N.; Kieran, Mark W.; Manley, Peter E.; Goumnerova, Liliana; Smith, Edward R.; Scott, R. Michael; London, Wendy B.; Ullrich, Nicole J.] Boston Childrens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Robison, Nathan J.; Sun, Pengling; Chi, Susan N.; Kieran, Mark W.; Manley, Peter E.; London, Wendy B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Prabhu, Sanjay P.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Cohen, Laurie E.] Boston Childrens Hosp, Div Endocrinol, Dept Med, Boston, MA 02115 USA. [Goumnerova, Liliana; Smith, Edward R.; Scott, R. Michael] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Ullrich, Nicole J.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Ullrich, NJ (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM nicole.ullrich@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 25 TC 4 Z9 8 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2013 VL 60 IS 10 BP 1630 EP 1635 DI 10.1002/pbc.24577 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 197XG UT WOS:000322885200022 PM 23670879 ER PT J AU Croteau, SE Luo, HY Lehmann, LE Chui, DHK Neufeld, EJ AF Croteau, Stacy E. Luo, Hong-Yuan Lehmann, Leslie E. Chui, David H. K. Neufeld, Ellis J. TI Novel dominant -thalassemia: Hb Boston-Kuwait [Codon 139/140(+T)] SO PEDIATRIC BLOOD & CANCER LA English DT Article DE chromouria; dipyrrole methylenes; stem cell transplant; unstable hemoglobin ID BETA-GLOBIN GENE; UNSTABLE HEMOGLOBIN; PHENOTYPE; MUTATION; DELETION; FAMILY; EXON-2; FRAMESHIFT; ANEMIA; TRAIT AB Dominant -thalassemias exhibit a hybrid phenotype of unstable hemoglobin and ineffective erythropoiesis. Most arise from heterozygous -globin gene mutations in exons 3 or 2 and present in adulthood as thalassemia intermedia. We report a novel, de novo -globin mutation presenting in a toddler with features of thalassemia major and chromaturia. Hemoglobin Boston-Kuwait is an elongated -chain variant (163 amino acids) that results from a frameshift mutation caused by a thymidine insertion in codons 139/140. Hematopoietic stem cell transplant provided a successful alternative therapy for this severe form of dominant -thalassemia. Pediatr Blood Cancer 2013;60:E131-E134. (c) 2013 Wiley Periodicals, Inc. C1 [Croteau, Stacy E.; Lehmann, Leslie E.; Neufeld, Ellis J.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Croteau, Stacy E.; Lehmann, Leslie E.; Neufeld, Ellis J.] Harvard Univ, Sch Med, Boston, MA USA. [Luo, Hong-Yuan; Chui, David H. K.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Croteau, SE (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, 450 Brookline Ave,Dana 3, Boston, MA 02215 USA. EM stacy.croteau@childrens.harvard.edu NR 24 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2013 VL 60 IS 10 BP E131 EP E134 DI 10.1002/pbc.24611 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 197XG UT WOS:000322885200007 PM 23776097 ER PT J AU Croteau, SE Henderson, ER Billett, AL Gebhardt, MC Voss, SD AF Croteau, Stacy E. Henderson, Eric R. Billett, Amy L. Gebhardt, Mark C. Voss, Stephan D. TI Resolving bony abnormality evolves to diffuse large B-cell lymphoma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE hyperostosis; malignant conversion; osteoid osteoma ID NON-HODGKINS-LYMPHOMA; CHILDREN AB Primary lymphoma of bone is a rare malignancy that can mimic infection and benign bone lesions radiographically. Malignant conversion of osseous lesions has been reported; evolution to lymphoma has not. We describe an adolescent male diagnosed with atypical osteoid osteoma who, despite near resolution of bony changes involving the anterior tibia, was diagnosed with monostotic diffuse large B-cell lymphoma four years later. Indolent lymphoma of the initial lesion is unlikely. This case highlights the importance of clinical suspicion of malignancy even with recurrence of similar clinical presentation and hints at possible osseous microenvironment abnormalities predisposing to the development of lymphoma. Pediatr Blood Cancer 2013;60:E113-E115. (c) 2013 Wiley Periodicals, Inc. C1 [Croteau, Stacy E.; Billett, Amy L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Croteau, Stacy E.; Billett, Amy L.] Boston Childrens Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA. [Henderson, Eric R.] Geisel Sch Med Dartmouth, Dartmouth Hitchcock Med Ctr, Lebanon, NH USA. [Gebhardt, Mark C.] Boston Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02215 USA. [Voss, Stephan D.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02215 USA. RP Croteau, SE (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, 450 Brookline Ave,Dana 3, Boston, MA 02215 USA. EM Stacy.Croteau@childrens.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2013 VL 60 IS 10 BP E113 EP E115 DI 10.1002/pbc.24609 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 197XG UT WOS:000322885200001 PM 23737071 ER PT J AU Kantardzhieva, A Liberman, MC Sewell, WF AF Kantardzhieva, Albena Liberman, M. Charles Sewell, William F. TI Quantitative analysis of ribbons, vesicles, and cisterns at the cat inner hair cell synapse: Correlations with spontaneous rate SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE synaptic ribbon; presynaptic density; active zone; vesicles; exocytosis; cochlea ID AUDITORY-NERVE FIBERS; PHOSPHATIDIC-ACID; AFFERENT SYNAPSES; MEMBRANE FISSION; PHOSPHOLIPASE-D; GOLGI MEMBRANE; CTBP/BARS; COCHLEA; REPLENISHMENT; ENDOCYTOSIS AB Cochlear hair cells form ribbon synapses with terminals of the cochlear nerve. To test the hypothesis that one function of the ribbon is to create synaptic vesicles from the cisternal structures that are abundant at the base of hair cells, we analyzed the distribution of vesicles and cisterns around ribbons from serial sections of inner hair cells in the cat, and compared data from low and high spontaneous rate (SR) synapses. Consistent with the hypothesis, we identified a "sphere of influence" of 350 nm around the ribbon, with fewer cisterns and many more synaptic vesicles. Although high- and low-SR ribbons tended to be longer and thinner than high-SR ribbons, the total volume of the two ribbon types was similar. There were almost as many vesicles docked at the active zone as attached to the ribbon. The major SR-related difference was that low-SR ribbons had more synaptic vesicles intimately associated with them. Our data suggest a trend in which low-SR synapses had more vesicles attached to the ribbon (51.3 vs. 42.8), more docked between the ribbon and the membrane (12 vs. 8.2), more docked at the active zone (56.9 vs. 44.2), and more vesicles within the "sphere of influence" (218 vs. 166). These data suggest that the structural differences between high-and low-SR synapses may be more a consequence, than a determinant, of the physiological differences. J. Comp. Neurol. J. Comp. Neurol. 521:3260-3271, 2013. (C) 2013 Wiley Periodicals, Inc. C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders [DC00767, DC09651, DC0188]; Hearing Health Foundation FX Grant sponsor: the National Institute on Deafness and Other Communication Disorders; Grand numbers: DC00767 and DC09651 (to W.F.S.) and DC0188 (to M.C.L.); Grant sponsor: the Hearing Health Foundation (to A.K.). NR 56 TC 14 Z9 14 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 1 PY 2013 VL 521 IS 14 BP 3260 EP 3271 DI 10.1002/cne.23345 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 188UP UT WOS:000322220700009 PM 23787810 ER PT J AU Iglesias, JE Sabuncu, MR Van Leemput, K AF Iglesias, Juan Eugenio Sabuncu, Mert Rory Van Leemput, Koen CA Alzheimer's Dis Neuroimaging Initi TI Improved inference in Bayesian segmentation using Monte Carlo sampling: Application to hippocampal subfield volumetry SO MEDICAL IMAGE ANALYSIS LA English DT Article; Proceedings Paper CT Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY 2012 CL Nice, FRANCE DE Bayesian modeling; Segmentation; Monte Carlo sampling; Hippocampal subfields ID IMAGE REGISTRATION TECHNIQUES; MILD COGNITIVE IMPAIRMENT; BRAIN-TUMOR SEGMENTATION; MR-IMAGES; AUTOMATIC SEGMENTATION; ALZHEIMERS-DISEASE; TISSUE CLASSIFICATION; MULTIPLE-SCLEROSIS; OUTLIER DETECTION; GENERATIVE MODEL AB Many segmentation algorithms in medical image analysis use Bayesian modeling to augment local image appearance with prior anatomical knowledge. Such methods often contain a large number of free parameters that are first estimated and then kept fixed during the actual segmentation process. However, a faithful Bayesian analysis would marginalize over such parameters, accounting for their uncertainty by considering all possible values they may take. Here we propose to incorporate this uncertainty into Bayesian segmentation methods in order to improve the inference process. In particular, we approximate the required marginalization over model parameters using computationally efficient Markov chain Monte Carlo techniques. We illustrate the proposed approach using a recently developed Bayesian method for the segmentation of hippocampal subfields in brain MRI scans, showing a significant improvement in an Alzheimer's disease classification task. As an additional benefit, the technique also allows one to compute informative "error bars" on the volume estimates of individual structures. (C) 2013 Elsevier B.V. All rights reserved. C1 [Iglesias, Juan Eugenio; Sabuncu, Mert Rory; Van Leemput, Koen] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Iglesias, Juan Eugenio; Sabuncu, Mert Rory; Van Leemput, Koen] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, Lyngby, Denmark. [Van Leemput, Koen] Aalto Univ, Dept Informat & Comp Sci, Helsinki, Finland. [Van Leemput, Koen] Aalto Univ, Dept Biomed Engn & Computat Sci, Helsinki, Finland. RP Iglesias, JE (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM iglesias@nmr.mgh.harvard.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Van Leemput, Koen/A-9197-2009; Saykin, Andrew/A-1318-2007; Iglesias, Juan Eugenio/K-1184-2014; Jack, Clifford/F-2508-2010 OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Van Leemput, Koen/0000-0001-6466-5309; Saykin, Andrew/0000-0002-1376-8532; Iglesias, Juan Eugenio/0000-0001-7569-173X; Jack, Clifford/0000-0001-7916-622X FU NCRR NIH HHS [1KL2RR025757-01, KL2 RR025757, P41 RR014075, P41-RR14075]; NIA NIH HHS [K01 AG030514, P30 AG008051, P30 AG010129, P50 AG005138, P50 AG008702, U01 AG024904]; NIBIB NIH HHS [R01EB006758, 1K25EB013649-01, K25 EB013649, R01 EB006758, R01 EB013565, R01EB013565]; NINDS NIH HHS [R01 NS052585, R01NS052585] NR 60 TC 12 Z9 12 U1 1 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD OCT PY 2013 VL 17 IS 7 BP 766 EP 778 DI 10.1016/j.media.2013.04.005 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 195GW UT WOS:000322691300006 PM 23773521 ER PT J AU Konukoglu, E Glocker, B Zikic, D Criminisi, A AF Konukoglu, Ender Glocker, Ben Zikic, Dark Criminisi, Antonio TI Neighbourhood approximation using randomized forests SO MEDICAL IMAGE ANALYSIS LA English DT Article; Proceedings Paper CT Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY 2012 CL Nice, FRANCE DE Approximate nearest neighbours; Random decision forests; Patch-based segmentation; Image-based regression; Supervised neighbour search ID SEGMENTATION; CLASSIFICATION; STRATEGIES; MANIFOLDS; AGE AB Leveraging available annotated data is an essential component of many modern methods for medical image analysis. In particular, approaches making use of the "neighbourhood" structure between images for this purpose have shown significant potential. Such techniques achieve high accuracy in analysing an image by propagating information from its immediate "neighbours" within an annotated database. Despite their success in certain applications, wide use of these methods is limited due to the challenging task of determining the neighbours for an out-of-sample image. This task is either computationally expensive due to large database sizes and costly distance evaluations, or infeasible due to distance definitions over semantic information, such as ground truth annotations, which is not available for out-of-sample images. This article introduces Neighbourhood Approximation Forests (NAFs), a supervised learning algorithm providing a general and efficient approach for the task of approximate nearest neighbour retrieval for arbitrary distances. Starting from an image training database and a user-defined distance between images, the algorithm learns to use appearance-based features to cluster images approximating the neighbourhood structured induced by the distance. NAF is able to efficiently infer nearest neighbours of an out-of-sample image, even when the original distance is based on semantic information. We perform experimental evaluation in two different scenarios: (i) age prediction from brain MRI and (ii) patch-based segmentation of unregistered, arbitrary field of view CT images. The results demonstrate the performance, computational benefits, and potential of NAF for different image analysis applications. (C) 2013 Elsevier B.V. All rights reserved. C1 [Konukoglu, Ender] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Glocker, Ben; Zikic, Dark; Criminisi, Antonio] Microsoft Res, Cambridge CB1 2FB, England. RP Konukoglu, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM ender.konukoglu@live.com OI Glocker, Ben/0000-0002-4897-9356 NR 51 TC 21 Z9 21 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 J9 MED IMAGE ANAL JI Med. Image Anal. PD OCT PY 2013 VL 17 IS 7 BP 790 EP 804 DI 10.1016/j.media.2013.04.013 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 195GW UT WOS:000322691300008 PM 23725639 ER PT J AU Sun, XB Cao, ZB Yeh, CK Sun, YY AF Sun, Xinbo Cao, Zhengbing Yeh, Chih-Ko Sun, Yuyu TI Antifungal activity, biofilm-controlling effect, and biocompatibility of poly(N-vinyl-2-pyrrolidinone)-grafted denture materials SO COLLOIDS AND SURFACES B-BIOINTERFACES LA English DT Article DE Drug delivery; Denture; Biofilm; Poly(N-vinyl-2-pyrrolidinone); Biocompatibility ID PLASMA SURFACE MODIFICATION; DRUG-DELIVERY SYSTEMS; CANDIDA-ALBICANS; BIOMEDICAL APPLICATIONS; ANTIBACTERIAL ACTIVITY; TISSUE CONDITIONERS; MICROBIAL BIOFILMS; DENTAL COMPOSITES; SILVER-ZEOLITE; IN-VITRO AB Colonization and biofilm-formation of Candida species on denture surfaces cause Candida-associated denture stomatitis (CADS), a common, recurring disease affecting up to 67% of denture wearers. We developed poly(N-vinyl-2-pyrrolidinone)-grafted denture materials that can be repeatedly recharged with various antifungal drugs to achieve long-term antifungal and biofilm-controlling effects. The monomer, N-vinyl-2-pyrrolidinone (NVP), was grafted onto poly(methyl methacrylate) denture resins through plasma-initiated grafting polymerization. The physical properties and biocompatibility of the resulting resins were not negatively affected by the presence of up to 7.92% of grafted poly (N-vinyl-2-pyrrolidinone) (PNVP). Miconazole and chlorhexidine digluconate (CD) were used as model antifungal drugs. PNVP grafting significantly increased the drug absorption capability of the resulting denture materials. Further, the new materials showed sustained drug release and provided anti fungal effects for weeks (in the case of CD) to months (in the case of miconazole). The drug-depleted resins could be recharged with the same or a different class of antifungal drug to further extend antifungal duration. If needed, drugs on the PNVP-grafted denture materials could be "washed out" (quenched) by treating with PNVP aqueous solutions to stop drug release. These results point to great potentials of the new materials in controlling biofilm-formation in a wide range of device-related applications. (c) 2013 Elsevier B.V. All rights reserved. C1 [Sun, Xinbo; Cao, Zhengbing] Medetech Dev Corp, Lynnwood, WA 98087 USA. [Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. [Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX 78229 USA. [Sun, Yuyu] Univ Massachusetts Lowell, Dept Chem, Lowell, MA 01854 USA. RP Sun, YY (reprint author), Univ Massachusetts Lowell, Dept Chem, Lowell, MA 01854 USA. EM yuyu_sun@uml.edu FU NIDCR, NIH [R01 DE021084]; VA Merit Review [1101BX001103] FX This study was supported by NIDCR, NIH (R01 DE021084) and VA Merit Review (1101BX001103). NR 70 TC 8 Z9 8 U1 1 U2 73 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0927-7765 J9 COLLOID SURFACE B JI Colloid Surf. B-Biointerfaces PD OCT 1 PY 2013 VL 110 BP 96 EP 104 DI 10.1016/j.colsurfb.2013.04.043 PG 9 WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials SC Biophysics; Chemistry; Materials Science GA 185BM UT WOS:000321940200014 PM 23708753 ER PT J AU Wang, LY Murphy, RR Hanscom, B Li, G Millard, SP Petrie, EC Galasko, DR Sikkema, C Raskind, MA Wilkinson, CW Peskind, ER AF Wang, Lucy Y. Murphy, Richard R. Hanscom, Brett Li, Ge Millard, Steven P. Petrie, Eric C. Galasko, Douglas R. Sikkema, Carl Raskind, Murray A. Wilkinson, Charles W. Peskind, Elaine R. TI Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span SO NEUROBIOLOGY OF AGING LA English DT Article DE Noradrenergic system; Norepinephrine; Cognition; Aging ID ALZHEIMERS-DISEASE; PLASMA NOREPINEPHRINE; NORADRENERGIC MODULATION; PREFRONTAL CORTEX; LOCUS-COERULEUS; WORKING-MEMORY; STRESS; CORTISOL; KINETICS; ENHANCEMENT AB Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21-100 years. After adjusting for age, gender, education, and ethnicity, higher CSF NE levels (units of 100 pg/mL) are associated with poorer performance on tests of attention, processing speed, and executive function (Trail Making A: regression coefficient 1.5, standard error [SE] 0.77, p = 0.046; Trail Making B: regression coefficient 5.0, SE 2.2, p = 0.024; Stroop Word-Color Interference task: regression coefficient 6.1, SE 2.0, p = 0.003). Findings are consistent with the earlier literature relating excess noradrenergic activity with cognitive impairment. Published by Elsevier Inc. C1 [Wang, Lucy Y.; Murphy, Richard R.; Li, Ge; Millard, Steven P.; Petrie, Eric C.; Raskind, Murray A.; Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res & Educ Clin Ctr, Seattle, WA USA. [Wang, Lucy Y.; Li, Ge; Petrie, Eric C.; Raskind, Murray A.; Wilkinson, Charles W.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Murphy, Richard R.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Hanscom, Brett] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Sikkema, Carl; Wilkinson, Charles W.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Wang, LY (reprint author), VA Puget Sound Healthcare Syst, Mental Illness Res & Educ Clin Ctr, 1660 South Columbian Way,S-116 MIRECC, Seattle, WA 98115 USA. EM wanglucy@u.washington.edu FU VA Puget Sound Mental Illness Research, Education and Clinical Center (MIRECC); VA Puget Sound Geriatric Research, Education, and Clinical Center; VA Special Fellowship in Advanced Psychiatry (MIRECC); University of Washington's ADRC Pilot Study Award; NIH/NIA [P50AG005136] FX This study was supported by the VA Puget Sound Mental Illness Research, Education and Clinical Center (MIRECC), the VA Puget Sound Geriatric Research, Education, and Clinical Center, the VA Special Fellowship in Advanced Psychiatry (MIRECC), the University of Washington's ADRC Pilot Study Award, and NIH/NIA grant P50AG005136. NR 48 TC 3 Z9 3 U1 0 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2013 VL 34 IS 10 BP 2287 EP 2292 DI 10.1016/j.neurobiolaging.2013.04.007 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 187JM UT WOS:000322113800006 PM 23639207 ER PT J AU Sel, S Munzenberg, C Nass, N Kalinski, T Datan, M Auffarth, GU Toteberg-Harms, M Zenkel, M Kruse, FE Paulsen, F Schicht, M AF Sel, Saadettin Muenzenberg, Christoph Nass, Norbert Kalinski, Thomas Datan, Maja Auffarth, Gerd U. Toeteberg-Harms, Marc Zenkel, Matthias Kruse, Friedrich E. Paulsen, Friedrich Schicht, Martin TI The transcription factor Foxk1 is expressed in developing and adult mouse neuroretina SO GENE EXPRESSION PATTERNS LA English DT Article DE Foxk1; Transcription factor; Retinal development; Retinogenesis ID RETINA; CELLS; DIFFERENTIATION; IDENTIFICATION; GENES; PTF1A AB The forkhead transcription factor Foxk1 is an important regulator of myogenic progenitor cells. Since our previous data from mouse retina revealed that Foxk1 is upregulated in Ptf1a-deficient mice we investigated the spatial and temporal expression of Foxk1 during development of mouse retina. Expression of Foxk1 was analyzed on both mRNA and protein level. To identify Foxk1 transcripts, retina and cerebrum (positive control) of adult animals (postnatal day 90 (P90)) was subjected to reverse transcription polymerase chain reaction (RT-PCR) and sequencing of the amplified cDNA. The Foxk1 protein was analyzed in adult retina by Western blotting and in developing eyes at embryonic day (E) 13, 15, E17, P0, P4, P7, P10 and P90 by immunohistochemistry. Localization of Foxk1 expression was determined using cell-specific markers by double labelling. Foxk1 transcripts were detected in adult retina by RT-PCR and confirmed by sequencing. Western blot analysis confirmed the expression of Foxk1 protein in the adult retina. Immunohistochemical examination of developing eyes localized the protein to bipolar, amacrine and ganglion cells with an onset of Foxk1 expression from E15 onwards. The expression pattern during development suggests that Foxk1 may have an important role in retinal cells. (c) 2013 Elsevier B.V. All rights reserved. C1 [Sel, Saadettin; Zenkel, Matthias; Kruse, Friedrich E.] Univ Erlangen Nurnberg, Dept Ophthalmol, D-91054 Erlangen, Germany. [Sel, Saadettin; Auffarth, Gerd U.] Heidelberg Univ, Dept Ophthalmol, Heidelberg, Germany. [Muenzenberg, Christoph] Univ Halle Wittenberg, Dept Ophthalmol, D-06108 Halle, Germany. [Nass, Norbert; Kalinski, Thomas] Otto Von Guericke Univ, Inst Pathol, Magdeburg, Germany. [Datan, Maja] Ctr Regenerat Therapies Dresden, Dresden, Germany. [Toeteberg-Harms, Marc] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Paulsen, Friedrich; Schicht, Martin] Univ Erlangen Nurnberg, Inst Anat, Dept 2, D-91054 Erlangen, Germany. RP Sel, S (reprint author), Univ Erlangen Nurnberg, Dept Ophthalmol, Schwabachanlage 6, D-91054 Erlangen, Germany. EM saadettinsel@googlemail.com RI Toteberg-Harms, Marc/J-4954-2013; Nass, Norbert/A-5592-2011; OI Toteberg-Harms, Marc/0000-0002-2134-1336; Nass, Norbert/0000-0003-2563-0386; Sel, Saadettin/0000-0003-3307-3305; Auffarth, Gerd/0000-0002-6927-5251 FU Deutsche Forschungsgemeinschaft [SE 1995/1-1]; Wilhelm-Roux program from Martin Luther University Halle-Wittenberg [FKZ 10/41] FX This work was supported in part by the Deutsche Forschungsgemeinschaft (SE 1995/1-1) and the Wilhelm-Roux program (FKZ 10/41) from Martin Luther University Halle-Wittenberg. NR 26 TC 0 Z9 0 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD OCT PY 2013 VL 13 IS 7 BP 280 EP 286 DI 10.1016/j.gep.2013.05.003 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 181PA UT WOS:000321679800009 PM 23714736 ER PT J AU Kolasinski, J Takahashi, E Stevens, AA Benner, T Fischl, B Zollei, L Grant, PE AF Kolasinski, James Takahashi, Emi Stevens, Allison A. Benner, Thomas Fischl, Bruce Zoellei, Lilla Grant, P. Ellen TI Radial and tangential neuronal migration pathways in the human fetal brain: Anatomically distinct patterns of diffusion MRI coherence SO NEUROIMAGE LA English DT Article ID DEVELOPING CEREBRAL-CORTEX; CORTICAL GABAERGIC NEURONS; ADULT HUMAN BRAIN; GANGLIONIC EMINENCE; HUMAN NEOCORTEX; CELL-MIGRATION; INTERNEURON MIGRATION; INTERMEDIATE ZONE; BASAL FOREBRAIN; ORIGINS AB Corticogenesis is underpinned by a complex process of subcortical neuroproliferation, followed by highly orchestrated cellular migration. A greater appreciation of the processes involved in human fetal corticogenesis is vital to gaining an understanding of how developmental disturbances originating in gestation could establish a variety of complex neuropathology manifesting in childhood, or even in adult life. Magnetic resonance imaging modalities offer a unique insight into anatomical structure, and increasingly infer information regarding underlying microstructure in the human brain. In this study we applied a combination of high-resolution structural and diffusion-weighted magnetic resonance imaging to a unique cohort of three post-mortem fetal brain specimens, aged between 19 and 22 post-conceptual weeks. Specifically, we sought to assess patterns of diffusion coherence associated with subcortical neuroproliferative structures: the pallial ventricular/subventricular zone and subpallial ganglionic eminence. Two distinct three-dimensional patterns of diffusion coherence were evident: a clear radial pattern originating in ventaicular/subventricular zone, and a tangentio-radial patterns originating in ganglionic eminence. These patterns appeared to regress in a caudo-rostral and lateral-ventral to medial-dorsal direction across the short period of fetal development under study. Our findings demonstrate for the first time distinct patterns of diffusion coherence associated with known anatomical proliferative structures. The radial pattern associated with dorsopallial ventricular/subventricular zone and the tangentio-radial pattern associated with subpallial ganglionic eminence are consistent with reports of radial-glial mediated neuronal migration pathways identified during human corticogenesis, supported by our prior studies of comparative fetal diffusion MRI and histology. The ability to assess such pathways in the fetal brain using MR imaging offers a unique insight into three-dimensional trajectories beyond those visualized using traditional histological techniques. Our results suggest that ex-vivo fetal MRI is a potentially useful modality in understanding normal human development and various disease processes whose etiology may originate in aberrant fetal neuronal migration. (c) 2013 Elsevier Inc. All rights reserved. C1 [Kolasinski, James; Takahashi, Emi; Stevens, Allison A.; Benner, Thomas; Fischl, Bruce; Zoellei, Lilla; Grant, P. Ellen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02119 USA. [Takahashi, Emi; Zoellei, Lilla; Grant, P. Ellen] Harvard Univ, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Div Newborn Med,Dept Med,Med Sch, Boston, MA 02115 USA. [Kolasinski, James] Univ Oxford, Nuffield Dept Clin Neurosci, Ctr Funct Magnet Resonance Imaging Brain FMRIB, Oxford OX3 9DU, England. RP Takahashi, E (reprint author), Harvard Univ, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Div Newborn Med,Dept Med,Med Sch, Boston, MA 02115 USA. EM emi@nmr.mgh.harvard.edu OI Kolasinski, James/0000-0002-1599-6440 FU National Institute of Mental Health [MH081896, RC2MH089921, RC2MH090047, RC2MH089929]; von Clemm Fellowship at Harvard University; Eunice Shriver Kennedy National Institute of Child Health and Human Development (NICHD) [R21HD069001, K99HD061485]; Biomedical Technology Program of the National Center for Research Resources (NCRR); National Institutes of Health; NCRR Shared Instrumentation Grant Program [S10RR021110]; High-End Instrumentation Grant Program [S10RR021110] FX This study was conducted using postmortem human brain specimens from the tissue collection at the Department of Neurobiology at Yale University School of Medicine (supported by grant MH081896 from the National Institute of Mental Health), which form a part of the BrainSpan Consortium collection (http://www.brainspan.org). This work was supported by the von Clemm Fellowship at Harvard University (JK), the Eunice Shriver Kennedy National Institute of Child Health and Human Development (NICHD) R21HD069001 (ET) and K99HD061485 (LZ), and the National Institute of Mental Health (RC2MH089921, RC2MH090047, and RC2MH089929). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), and the National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically grant number S10RR021110. The content of the manuscript is the view of the authors and does not necessarily represent the official views of the Eunice Shriver Kennedy NICHD, NIMH, or NIH. NR 67 TC 15 Z9 15 U1 0 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2013 VL 79 BP 412 EP 422 DI 10.1016/j.neuroimage.2013.04.125 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 164LS UT WOS:000320412200040 PM 23672769 ER PT J AU Weisbart, RH Chan, G Li, E Farmani, N Heinze, E Rubell, A Nishimura, RN Colburn, K AF Weisbart, Richard H. Chan, Grace Li, Erica Farmani, Niloofar Heinze, Emil Rubell, Antonia Nishimura, Robert N. Colburn, Keith TI BRAF splice variants in rheumatoid arthritis synovial fibroblasts activate MAPK through CRAF SO MOLECULAR IMMUNOLOGY LA English DT Article DE Rheumatoid arthritis; Oncogene; MAPK cascade ID TYPE-1 MATRIX-METALLOPROTEINASE; MUTATIONS; CELLS; AUTOANTIBODIES; INFLAMMATION; INHIBITORS; CARTILAGE; CANCER AB Rheumatoid arthritis (RA) is a destructive polyarthritis in which synovial-like fibroblasts (SFs) invade and erode cartilage by expressing membrane-anchored type 1 matrix metalloproteinase (MT1-MMP). The mitogen activated protein kinase (MAPK) pathway is activated in RA SFs, but the mechanism of activation is unknown. Here we identify aberrant BRAF splice variants with deletions in both the kinase domain and RAS-binding domain (RBD) in SFs from the majority of RA patients and show that these BRAF splice variants constitutively activate MAPK through CRAF, increase expression of MT1-MMP, and enhance fibroblast invasion of collagen. Published by Elsevier Ltd. C1 [Weisbart, Richard H.; Chan, Grace; Li, Erica; Rubell, Antonia] Vet Affairs Greater Los Angeles Health Care Syst, Sepulveda, CA 91343 USA. [Farmani, Niloofar; Heinze, Emil] Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA. [Nishimura, Robert N.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Colburn, Keith] Vet Affairs Med Ctr, Loma Linda, CA 92357 USA. [Colburn, Keith] Loma Linda Univ, Loma Linda, CA 92350 USA. RP Weisbart, RH (reprint author), Vet Affairs Greater Los Angeles Health Care Syst, Dept Res, 16111 Plummer St 111S, Sepulveda, CA USA. EM rweisbar@ucla.edu FU Veterans Affairs FX This work was sponsored by a grant from the Veterans Affairs. NR 30 TC 2 Z9 5 U1 1 U2 51 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 2013 VL 55 IS 3-4 BP 247 EP 252 DI 10.1016/j.molimm.2013.02.001 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 152OE UT WOS:000319540200008 PM 23517740 ER PT J AU Isono, K Endo, TA Ku, MC Yamada, D Suzuki, R Sharif, J Ishikura, T Toyoda, T Bernstein, BE Koseki, H AF Isono, Kyoichi Endo, Takaho A. Ku, Manching Yamada, Daisuke Suzuki, Rie Sharif, Jafar Ishikura, Tomoyuki Toyoda, Tetsuro Bernstein, Bradley E. Koseki, Haruhiko TI SAM Domain Polymerization Links Subnuclear Clustering of PRC1 to Gene Silencing SO DEVELOPMENTAL CELL LA English DT Article ID POLYCOMB-GROUP PROTEINS; NUCLEAR REORGANIZATION; H2A UBIQUITYLATION; HOX GENES; CHROMATIN; COMPLEX; DROSOPHILA; MOUSE; MEDIATE; RING1B AB The Polycomb-group (PcG) repressive complex-1 (PRC1) forms microscopically visible clusters in nuclei; however, the impact of this cluster formation on transcriptional regulation and the underlying mechanisms that regulate this process remain obscure. Here, we report that the sterile alpha motif (SAM) domain of a PRC1 core component Phc2 plays an essential role for PRC1 clustering through head-to-tail macromolecular polymerization, which is associated with stable target binding of PRC1/PRC2 and robust gene silencing activity. We propose a role for SAM domain polymerization in this repression by two distinct mechanisms: first, through capturing and/or retaining PRC1 at the PcG targets, and second, by strengthening the interactions between PRC1 and PRC2 to stabilize transcriptional repression. Our findings reveal a regulatory mechanism mediated by SAM domain polymerization for PcG-mediated repression of developmental loci that enables a robust yet reversible gene repression program during development. C1 [Isono, Kyoichi; Yamada, Daisuke; Suzuki, Rie; Sharif, Jafar; Ishikura, Tomoyuki; Koseki, Haruhiko] Japan Sci & Technol Agcy, RIKEN Ctr Integrat Med Sci IMS RCAI, Lab Dev Genet, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Endo, Takaho A.] Japan Sci & Technol Agcy, RIKEN IMS RCAI, Lab Integrat Genom, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Toyoda, Tetsuro] Japan Sci & Technol Agcy, RIKEN, Adv Ctr Comp & Commun, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Isono, Kyoichi; Koseki, Haruhiko] Japan Sci & Technol Agcy, CREST, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Isono, Kyoichi] Japan Sci & Technol Agcy, PREST, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Ku, Manching; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ku, Manching; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Isono, K (reprint author), Japan Sci & Technol Agcy, RIKEN Ctr Integrat Med Sci IMS RCAI, Lab Dev Genet, Tsurumi Ku, 1-7-22 Suehiro, Yokohama, Kanagawa 2300045, Japan. EM isono@rcai.riken.jp; koseki@rcai.riken.jp RI Koseki, Haruhiko/I-3825-2014; Endo, Takaho/B-5763-2017 OI Koseki, Haruhiko/0000-0001-8424-5854; Endo, Takaho/0000-0002-2801-2463 FU Ministry of Education, Culture, Sports, Science and Technology of Japan; PRESTO program of Japan Science and Technology Agency; CREST program of Japan Science and Technology Agency FX We would like to thank Drs. S. Kobayakawa, K. Abe, M. Vidal, W. Bickmore, and T. Kamijo for the reagents used in this study. We also thank M. Kumon and M. Fujita for help this work. This work was supported by Grants-in-Aid for Scientific Research and for Scientific Research (to K.I. and H.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and PRESTO (to K.I.) and CREST (to H.K.) programs of Japan Science and Technology Agency. NR 40 TC 57 Z9 57 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD SEP 30 PY 2013 VL 26 IS 6 BP 565 EP 577 DI 10.1016/j.devcel.2013.08.016 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 243GO UT WOS:000326305100007 PM 24091011 ER PT J AU Mahler, SA Miller, CD Hollander, JE Nagurney, JT Birkhahn, R Singer, AJ Shapiro, NI Glynn, T Nowak, R Safdar, B Peberdy, M Counselman, FL Chandra, A Kosowsky, J Neuenschwander, J Schrock, JW Plantholt, S Diercks, DB Peacock, WF AF Mahler, Simon A. Miller, Chadwick D. Hollander, Judd E. Nagurney, John T. Birkhahn, Robert Singer, Adam J. Shapiro, Nathan I. Glynn, Ted Nowak, Richard Safdar, Basmah Peberdy, Mary Counselman, Francis L. Chandra, Abhinav Kosowsky, Joshua Neuenschwander, James Schrock, Jon W. Plantholt, Stephen Diercks, Deborah B. Peacock, W. Frank TI Identifying patients for early discharge: Performance of decision rules among patients with acute chest pain SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Chest pain; Risk stratification; Clinical decision rules; Acute coronary syndrome ID ACUTE CORONARY SYNDROMES; EMERGENCY-DEPARTMENT PATIENTS; MYOCARDIAL-INFARCTION; RISK STRATIFICATION; TROPONIN ASSAYS; EARLY-DIAGNOSIS; ROC CURVE; GUIDELINES; EVENTS; SCORE AB Background: The HEART score and North American Chest Pain Rule (NACPR) are decision rules designed to identify acute chest pain patients for early discharge without stress testing or cardiac imaging. This study compares the clinical utility of these decision rules combined with serial troponin determinations. Methods and results: A secondary analysis was conducted of 1005 participants in the Myeloperoxidase In the Diagnosis of Acute coronary syndromes Study (MIDAS). MIDAS is a prospective observational cohort of Emergency Department (ED) patients enrolled from 18 US sites with symptoms suggestive of acute coronary syndrome (ACS). The ability to identify participants for early discharge and the sensitivity for ACS at 30 days were compared among an unstructured assessment, NACPR, and HEART score, each combined with troponin measures at 0 and 3 h. ACS, defined as cardiac death, acute myocardial infarction, or unstable angina, occurred in 22% of the cohort. The unstructured assessment identified 13.5% (95% CI 11.5-16%) of participants for early discharge with 98% (95% CI 95-99%) sensitivity for ACS. The NACPR identified 4.4% (95% CI 3-6%) for early discharge with 100% (95% CI 98-100%) sensitivity for ACS. The HEART score identified 20% (95% CI 18-23%) for early discharge with 99% (95% CI 97-100%) sensitivity for ACS. The HEART score had a net reclassification improvement of 10% (95% CI 8-12%) versus unstructured assessment and 19% (95% CI 17-21%) versus NACPR. Conclusions: The HEART score with 0 and 3 hour serial troponin measures identifies a substantial number of patients for early discharge while maintaining high sensitivity for ACS. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Mahler, Simon A.; Miller, Chadwick D.] Wake Forest Sch Med, Winston Salem, NC 27157 USA. [Hollander, Judd E.] Univ Penn, Philadelphia, PA 19104 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Birkhahn, Robert] New York Methodist Hosp, Brooklyn, NY USA. [Singer, Adam J.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Shapiro, Nathan I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Glynn, Ted] Ingham Reg Med Ctr, Lansing, MI USA. [Nowak, Richard] Henry Ford Hlth Syst, Detroit, MI USA. [Safdar, Basmah] Yale Univ, New Haven, CT USA. [Peberdy, Mary] Virginia Commonwealth Univ, Richmond, VA USA. [Counselman, Francis L.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Chandra, Abhinav] Duke Univ, Durham, NC USA. [Kosowsky, Joshua] Brigham & Womens Hosp, Boston, MA 02115 USA. [Neuenschwander, James] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Schrock, Jon W.] Metro Hlth Med Ctr, Cleveland, OH USA. [Plantholt, Stephen] St Agnes Hosp, Baltimore, MD USA. [Diercks, Deborah B.] Univ Calif Davis, Sacramento, CA 95817 USA. [Peacock, W. Frank] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Mahler, SA (reprint author), Wake Forest Sch Med, Dept Epidemiol & Prevent & Emergency Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM smahler@wakehealth.edu RI Shapiro, Nathan/F-1718-2016; OI Hollander, Judd/0000-0002-1318-2785 FU Biosite; NIH [T32 HL 87730]; Siemens; 3M; PA Department of Health; American Heart Association; Alere; MediciNova; Astute Medical Inc.; Bristol-Myers Squibb; NY Department of Health; NINDS; Clendevor; NHLBI FX The MIDAS trial was funded by Biosite. In addition, Dr. Mahler receives funding from NIH T32 HL 87730. Disclosures (past 12 months): Miller: research support from Siemens, 3M, PA Department of Health, American Heart Association, NIH. Provisional patent filing related to the prediction of coronary disease; Birkhahn: research support from Biosite, Alere, MediciNova, Astute Medical Inc., Bristol-Myers Squibb, NY Department of Health, NINDS; Nagurney: research support from Biosite, Alere, Clendevor, and NHLBI. NR 23 TC 25 Z9 25 U1 2 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 30 PY 2013 VL 168 IS 2 BP 795 EP 802 DI 10.1016/j.ijcard.2012.10.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231JN UT WOS:000325412800047 PM 23117012 ER PT J AU Vergallo, R Yonetsu, T Kato, K Jia, HB Abtahian, F Tian, JW Hu, SN McNulty, I Yu, B Biasucci, LM Crea, F Jang, IK AF Vergallo, Rocco Yonetsu, Taishi Kato, Koji Jia, Haibo Abtahian, Farhad Tian, Jinwei Hu, Sining McNulty, Iris Yu, Bo Biasucci, Luigi M. Crea, Filippo Jang, Ik-Kyung TI Evaluation of culprit lesions by optical coherence tomography in patients with ST-elevation myocardial infarction SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Optical coherence tomography; Thrombus; ST-elevation myocardial infarction ID PLAQUE C1 [Vergallo, Rocco; Yonetsu, Taishi; Kato, Koji; Jia, Haibo; Abtahian, Farhad; Tian, Jinwei; Hu, Sining; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Yu, Bo] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Key Lab Myocardial Ischemia,Chinese Minist Educ, Harbin 150086, Peoples R China. [Biasucci, Luigi M.; Crea, Filippo] Univ Cattolica Sacro Cuore, A Gemelli Hosp, I-00168 Rome, Italy. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org OI biasucci, luigi m/0000-0002-6921-6497 NR 5 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 30 PY 2013 VL 168 IS 2 BP 1592 EP 1593 DI 10.1016/j.ijcard.2013.01.041 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231JN UT WOS:000325412800196 PM 23415175 ER PT J AU Ozcan, C Barrett, CD AF Ozcan, Cevher Barrett, Conor D. TI Ventricular arrhythmias and left ventricular assist device SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Arrhythmia; Circulatory assist devices; Defibrillation; Heart failure ID SUPPORT C1 [Ozcan, Cevher; Barrett, Conor D.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ozcan, Cevher] SUNY Buffalo, Sch Med & Biomed Sci, Div Cardiovasc Med, Buffalo, NY 14203 USA. RP Ozcan, C (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Clin & Translat Res Ctr, Suite 7030,875 Ellicott St, Buffalo, NY 14203 USA. EM cevheroz@buffalo.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 30 PY 2013 VL 168 IS 2 BP E81 EP E83 DI 10.1016/j.ijcard.2013.07.045 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231JN UT WOS:000325412800018 PM 23890887 ER PT J AU Byrareddy, SN Ayash-Rashkovsky, M Kramer, VG Lee, SJ Correll, M Novembre, FJ Villinger, F Johnson, WE von Gegerfelt, A Felber, BK Ruprecht, RM AF Byrareddy, Siddappa N. Ayash-Rashkovsky, Mila Kramer, Victor G. Lee, Sandra J. Correll, Mick Novembre, Francis J. Villinger, Francois Johnson, Welkin E. von Gegerfelt, Agneta Felber, Barbara K. Ruprecht, Ruth M. TI Live Attenuated Rev-Independent Nef(-)SIV Enhances Acquisition of Heterologous SIVsmE660 in Acutely Vaccinated Rhesus Macaques SO PLOS ONE LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; BLOOD-BANK COHORT; CONTROL REPLICATION; NEONATAL MACAQUES; MUCOSAL INFECTION; MICROARRAY DATA; ADULT MACAQUES; SURVIVAL-TIME; HIV-1 VACCINE; SIV VACCINES AB Background: Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef(-) simian immunodeficiency virus (Rev-Ind Nef(-)SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges. Methodology/Principal Findings: Three groups of four RM were inoculated with Rev-Ind Nef(-)SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef(-)SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef(-)SIV. Conclusions/Significance: We conclude that although Rev-Ind Nef(-)SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges. C1 [Byrareddy, Siddappa N.; Ayash-Rashkovsky, Mila; Kramer, Victor G.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Byrareddy, Siddappa N.; Ayash-Rashkovsky, Mila; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Sandra J.; Correll, Mick] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Correll, Mick] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Novembre, Francis J.; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Novembre, Francis J.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Johnson, Welkin E.] Boston Coll, Dept Biol, Boston, MA USA. [von Gegerfelt, Agneta; Felber, Barbara K.] Ctr Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD USA. [von Gegerfelt, Agneta; Felber, Barbara K.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. RP Byrareddy, SN (reprint author), Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. EM siddappa.n.byrareddy@emory.edu OI Byrareddy, Siddappa /0000-0002-7423-1763 FU National Institutes of Health [R01 RR014180, P01 AI048240]; NIH [R01 AI083118]; Intramural Research Program of the National Cancer Institute, NIH; National Center for Research Resources [P51RR169]; Office of Research Infrastructure Programs/OD [P51OD11107] FX This study was supported by National Institutes of Health grants R01 RR014180, P01 AI048240 to RMR, NIH R01 AI083118 to WEJ, and the Intramural Research Program of the National Cancer Institute, NIH to BKF. This project was also funded by the National Center for Research Resources grant P51RR169 and is currently supported by the Office of Research Infrastructure Programs/OD P51OD11107. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 2 Z9 3 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 30 PY 2013 VL 8 IS 9 AR e75556 DI 10.1371/journal.pone.0075556 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231NL UT WOS:000325423500073 PM 24098702 ER PT J AU Tzika, AA Constantinou, C Bandyopadhaya, A Psychogios, N Lee, S Mindrinos, M Martyn, JAJ Tompkins, RG Rahme, LG AF Tzika, A. Aria Constantinou, Caterina Bandyopadhaya, Arunava Psychogios, Nikolaos Lee, Sangseok Mindrinos, Michael Martyn, J. A. Jeevendra Tompkins, Ronald G. Rahme, Laurence G. TI A Small Volatile Bacterial Molecule Triggers Mitochondrial Dysfunction in Murine Skeletal Muscle SO PLOS ONE LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; ACTIVATED-RECEPTOR-GAMMA; FREE FATTY-ACIDS; MUCOID PSEUDOMONAS-AERUGINOSA; LIPOPROTEIN-LIPASE ACTIVITY; CYSTIC-FIBROSIS LUNG; INSULIN-RESISTANCE; PPAR-GAMMA; IN-VIVO; P-31 NMR AB Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute and chronic infection in human tissues, including in the lungs of cystic fibrosis (CF) patients, acts as an interkingdom immunomodulatory signal that facilitates pathogen persistence, and host tolerance to infection. Transcriptome results have led to the hypothesis that 2-AA causes further harm to the host by triggering mitochondrial dysfunction in skeletal muscle. As normal skeletal muscle function is essential to survival, and is compromised in many chronic illnesses, including infections and CF-associated muscle wasting, we here determine the global effects of 2-AA on skeletal muscle using high-resolution magic-angle-spinning (HRMAS), proton (1 H) nuclear magnetic resonance (NMR) metabolomics, in vivo P-31 NMR, whole-genome expression analysis and functional studies. Our results show that 2-AA when injected into mice, induced a biological signature of insulin resistance as determined by 1 H NMR analysis-, and dramatically altered insulin signaling, glucose transport, and mitochondrial function. Genes including Glut4, IRS1, PPAR-c, PGC1 and Sirt1 were downregulated, whereas uncoupling protein UCP3 was up-regulated, in accordance with mitochondrial dysfunction. Although 2-AA did not alter high-energy phosphates or pH by in vivo P-31 NMR analysis, it significantly reduced the rate of ATP synthesis. This affect was corroborated by results demonstrating down-regulation of the expression of genes involved in energy production and muscle function, and was further validated by muscle function studies. Together, these results further demonstrate that 2-AA, acts as a mediator of interkingdom modulation, and likely effects insulin resistance associated with a molecular signature of mitochondrial dysfunction in skeletal muscle. Reduced energy production and mitochondrial dysfunctional may further favor infection, and be an important step in the establishment of chronic and persistent infections. C1 [Tzika, A. Aria; Constantinou, Caterina; Bandyopadhaya, Arunava; Psychogios, Nikolaos; Tompkins, Ronald G.; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Tzika, A. Aria; Constantinou, Caterina; Bandyopadhaya, Arunava; Psychogios, Nikolaos; Lee, Sangseok; Martyn, J. A. Jeevendra; Tompkins, Ronald G.; Rahme, Laurence G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tzika, A. Aria; Psychogios, Nikolaos] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Mindrinos, Michael] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. [Lee, Sangseok; Martyn, J. A. Jeevendra] Harvard Univ, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA USA. [Tzika, A. Aria; Constantinou, Caterina; Bandyopadhaya, Arunava; Psychogios, Nikolaos; Lee, Sangseok; Martyn, J. A. Jeevendra; Rahme, Laurence G.] Shriners Hosp Children Boston, Boston, MA USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM atzika@hms.harvard.edu; rahme@molbio.mgh.harvard.edu OI Psychogios, Nikolaos/0000-0002-2747-6012; Constantinou, Caterina/0000-0003-3589-0739; Lee, Sangseok/0000-0001-7023-3668 FU Shriner's Hospital for Children [87100]; Center grant of the National Institutes of Health FX This work was supported in part by a Shriner's Hospital for Children research grant no. 87100 to Laurence G. Rahme, and by a Center grant of the National Institutes of Health to the Stanford Genome Technology Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 93 TC 9 Z9 9 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 30 PY 2013 VL 8 IS 9 AR e74528 DI 10.1371/journal.pone.0074528 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231NL UT WOS:000325423500026 PM 24098655 ER PT J AU Westover, MB Shafi, MM Ching, SN Chemali, JJ Purdon, PL Cash, SS Brown, EN AF Westover, M. Brandon Shafi, Mouhsin M. Ching, ShiNung Chemali, Jessica J. Purdon, Patrick L. Cash, Sydney S. Brown, Emery N. TI Real-time segmentation of burst suppression patterns in critical care EEG monitoring SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Burst suppression; Medically-induced coma; Quantitative EEG; ICU EEG monitoring ID REFRACTORY STATUS EPILEPTICUS; BISPECTRAL INDEX; PROGNOSTIC VALUE; ANESTHESIA; ISOFLURANE; COMA; ELECTROENCEPHALOGRAM; HYPOTHERMIA; INFUSIONS; DEPTH AB Objective: Develop a real-time algorithm to automatically discriminate suppressions from non-suppressions (bursts) in electroencephalograms of critically ill adult patients. Methods: A real-time method for segmenting adult ICU EEG data into bursts and suppressions is presented based on thresholding local voltage variance. Results are validated against manual segmentations by two experienced human electroencephalographers. We compare inter-rater agreement between manual EEG segmentations by experts with inter-rater agreement between human vs automatic segmentations, and investigate the robustness of segmentation quality to variations in algorithm parameter settings. We further compare the results of using these segmentations as input for calculating the burst suppression probability (BSP), a continuous measure of depth-of-suppression. Results: Automated segmentation was comparable to manual segmentation, i.e. algorithm-vs-human agreement was comparable to human-vs-human agreement, as judged by comparing raw EEG segmentations or the derived BSP signals. Results were robust to modest variations in algorithm parameter settings. Conclusions: Our automated method satisfactorily segments burst suppression data across a wide range adult ICU EEG patterns. Performance is comparable to or exceeds that of manual segmentation by human electroencephalographers. Significance: Automated segmentation of burst suppression EEG patterns is an essential component of quantitative brain activity monitoring in critically ill and anesthetized adults. The segmentations produced by our algorithm provide a basis for accurate tracking of suppression depth. (C) 2013 Elsevier B.V. All rights reserved. C1 [Westover, M. Brandon; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ching, ShiNung; Chemali, Jessica J.; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Brain & Cognit Sci, Boston, MA 02114 USA. [Chemali, Jessica J.; Purdon, Patrick L.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM mwestover@partners.org; mshafi@bidmc.harvard.edu; shinung@neurostat.mit.edu; jessica.chemali@gmail.com; patrickp@nmr.mgh.harvard.edu; scash@partners.org; enb@neurostat.mit.edu FU American Brain Foundation; NIH/NINDS [NS062092]; NIH [DP1OD003646, R01-MH071847, DP2-OD006454, K25-NS057580] FX This study was supported by the following grants: American Brain Foundation (MBW), NIH/NINDS NS062092 (MBW, SSC); NIH Director's Pioneer Award DP1OD003646 and NIH R01-MH071847 (ENB, SC), and NIH New Innovator Award DP2-OD006454 and K-Award K25-NS057580 (PLP). NR 42 TC 5 Z9 5 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP 30 PY 2013 VL 219 IS 1 BP 131 EP 141 DI 10.1016/j.jneumeth.2013.07.003 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 222HX UT WOS:000324722900015 ER PT J AU Milanak, ME Gros, DF Magruder, KM Brawman-Mintzer, O Frueh, BC AF Milanak, Melissa E. Gros, Daniel F. Magruder, Kathryn M. Brawman-Mintzer, Olga Frueh, B. Christopher TI Prevalence and features of generalized anxiety disorder in Department of Veteran Affairs primary care settings SO PSYCHIATRY RESEARCH LA English DT Article DE Posttraumatic stress disorder; Veterans; Comorbidity; Healthcare utilization ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; VA PRIMARY-CARE; PSYCHOMETRIC PROPERTIES; MENTAL-HEALTH; MAJOR DEPRESSION; US VETERANS; DSM-IV; COMORBIDITY; CLINICS AB Generalized anxiety disorder (GAD) is a highly prevalent distressing condition for individuals in both community and community primary care settings. However, despite the high prevalence of GAD identified in epidemiological studies, little is known about GAD and its related symptoms and impairments in veteran populations. The present study investigated the prevalence, comorbidity, physical and mental health impairment, and healthcare utilization of veteran participants with GAD, as well as comparing symptoms of GAD and posttraumatic stress disorder (PTSD). Veterans (N=884) participated in a cross-sectional investigation in primary care clinics in four Veteran Affairs Medical Centers (VAMCs) and completed diagnostic interviews and self-report questionnaires; a chart review was conducted to assess their VAMC healthcare utilization. A large number of participants (12%) met diagnostic criteria for GAD, reporting significantly worse emotional health, pain, and general health, in addition to increased mental healthcare utilization and antidepressant medications. In addition, GAD was found in 40% of participants with PTSD, resulting in more severe symptoms and impairment than in patients with GAD alone. These findings provide evidence of high prevalence and severe impairment associated with GAD in veterans and highlight the need for improved recognition, assessment, and treatments for GAD. (c) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Milanak, Melissa E.; Gros, Daniel F.; Magruder, Kathryn M.; Brawman-Mintzer, Olga] Med Univ S Carolina, Charleston, SC 29403 USA. [Gros, Daniel F.; Magruder, Kathryn M.; Brawman-Mintzer, Olga] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Milanak, ME (reprint author), Med Univ S Carolina, Natl Crime Victims Ctr, 67 President St, Charleston, SC 29403 USA. EM milanak@musc.edu FU Veterans Affairs Health Services Research and Development [VCR-99-010-2] FX This work was partially supported by a grant from Veterans Affairs Health Services Research and Development (VCR-99-010-2). NR 36 TC 11 Z9 11 U1 4 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD SEP 30 PY 2013 VL 209 IS 2 BP 173 EP 179 DI 10.1016/j.psychres.2013.03.031 PG 7 WC Psychiatry SC Psychiatry GA 223GA UT WOS:000324791500008 PM 23659756 ER PT J AU Chao, L Weiner, M Neylan, T AF Chao, Linda Weiner, Michael Neylan, Thomas TI Regional cerebral volumes in veterans with current versus remitted posttraumatic stress disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Posttraumatic stress disorder; Magnetic resonance imaging; Hippocampus; Anterior cingulate; Insula ID SURFACE-BASED ANALYSIS; HIPPOCAMPAL VOLUME; GRAY-MATTER; AMYGDALA VOLUME; BRAIN VOLUME; GULF-WAR; CHILDHOOD MALTREATMENT; ANOREXIA-NERVOSA; DENTATE GYRUS; SEXUAL-ABUSE AB We previously reported that hippocampal volume was associated with current, but not lifetime posttraumatic stress disorder (PTSD) symptom severity. In the present study, we test the hypothesis that like the hippocampus, the volumes of other brain regions previously implicated in PTSD, are also negatively related to current, but not lifetime PTSD symptom severity. One hundred ninety-one veterans underwent structural magnetic resonance imaging (MRI) on a 4 T scanner. Seventy-five veterans were trauma unexposed, 43 were trauma exposed without PTSD, 39 were trauma exposed with current PTSD, and 34 were trauma exposed veterans with remitted PTSD. Hippocampal, amygdala, rostral and caudal anterior cingulate, insula, and corpus callosum volumes, quantified with Freesurfer version 4.5, were analyzed by group using multivariate analysis of covariance. Veterans with PTSD had smaller hippocampal, caudal anterior cingulate, insula, and corpus callosum volumes than the unexposed controls (p <= 0.009); smaller hippocampal, caudal anterior cingulate, insula (p <= 0.009) and marginally smaller corpus callosum (p=0.06) than veterans with remitted PTSD; and smaller hippocampal and caudal anterior cingulate volumes than veterans without PTSD (p <= 0.04). In contrast, there was no significant volume differences between veterans with remitted PTSD compared to those without PTSD or unexposed controls. The finding that current but not lifetime PTSD accounts for the volumes of multiple brain regions suggests that either smaller brain volume is a vulnerability factor that impedes recovery from PTSD or that recovery from PTSD is accompanied by a wide-spread restoration of brain tissue. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Chao, Linda; Weiner, Michael] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94121 USA. [Chao, Linda; Weiner, Michael] Univ Calif San Francisco, Dept Biomed Imaging, San Francisco, CA 94121 USA. [Chao, Linda; Weiner, Michael; Neylan, Thomas] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Chao, Linda; Weiner, Michael] Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Neylan, Thomas] Dept Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. RP Chao, L (reprint author), Univ Calif San Francisco, San Francisco VAMC, Dept Radiol, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu FU Mental Illness Research and Education Clinical Center of the US Veterans Health Administration, Office of Research and Development, Department of Defense [W81XWH-05-2-0094]; Mental Illness Research and Education Clinical Center of Department of Veterans Affairs VA GWI [B3776] FX This study was supported in part by grants from the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration, Office of Research and Development, Department of Defense (No. W81XWH-05-2-0094), and Department of Veterans Affairs VA GWI (No. B3776). Resources and the use of facilities were provided by the Veterans Administration Medical Center, San Francisco, California. NR 96 TC 19 Z9 21 U1 1 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP 30 PY 2013 VL 213 IS 3 BP 193 EP 201 DI 10.1016/j.pscychresns.2013.03.002 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 211TV UT WOS:000323934800003 PM 23816189 ER PT J AU Henry, ME Lauriat, TL Lowen, SB Churchill, JH Hodgkinson, CA Goldman, D Renshaw, PF AF Henry, Michael E. Lauriat, Tara L. Lowen, Steven B. Churchill, Jeffrey H. Hodgkinson, Colin A. Goldman, David Renshaw, Perry F. TI Effects of citalopram and escitalopram on fMRI response to affective stimuli in healthy volunteers selected by serotonin transporter genotype SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Functional magnetic resonance imaging; Pharmaco-fMRI; Antidepressant; Imaging genetics; Affective stimulus ID EMOTIONAL FACIAL EXPRESSIONS; MAJOR DEPRESSION; HUMAN AMYGDALA; FUNCTIONAL CONNECTIVITY; MOOD STATE; METAANALYSIS; FACES; BRAIN; GENE; ACTIVATION AB This study was designed to assess whether functional magnetic resonance imaging (fMRI) following antidepressant administration (pharmaco-fMRI) is sufficiently sensitive to detect differences in patterns of activation between enantiomers of the same compound. Healthy adult males (n = 11) participated in a randomized, double-blind, cross-over trial with three medication periods during which they received citalopram (racemic mixture), escitalopram (S-citalopram alone), or placebo for 2 weeks. All participants had high expression serotonin transporter genotypes. An fMRI scan that included passive viewing of overt and covert affective faces and affective words was performed after each medication period. Activation in response to overt faces was greater following escitalopram than following citalopram in the right insula, thalamus, and putamen when the faces were compared with a fixation stimulus. For the rapid covert presentation, a greater response was observed in the left middle temporal gyrus in the happy versus fearful contrast following escitalopram than following citalopram. Thus, the combination of genomics and fMRI was successful in discriminating between two very similar drugs. However, the pattern of activation observed suggests that further studies are indicated to understand how to optimally combine the two techniques. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Henry, Michael E.; Lauriat, Tara L.; Churchill, Jeffrey H.] St Elizabeths Med Ctr, Dept Psychiat, Boston, MA 02135 USA. [Henry, Michael E.; Lauriat, Tara L.; Lowen, Steven B.] McLean Hosp, McLean Imaging Ctr, Belmont, MA 02478 USA. [Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. [Renshaw, Perry F.] Univ Utah, Inst Brain, Salt Lake City, UT 84112 USA. RP Henry, ME (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM mhenry14@partners.org RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lauriat, Tara/0000-0003-0729-9386 FU Forest Research Institute FX The study was funded by Forest Research Institute as an Investigator-Initiated Trial awarded to MEH. Escitalopram was supplied by Forest and metabolite assays were performed in their analytical laboratory. We thank Hanady Gouta, Athari Alyazidi, and Sophia Shrand for assistance with subject screenings; Ayu Tesfaye for investigational pharmacy services; Cherisse Ferrier for serotonin transporter genotyping; and Bonnie Adams for performing magnetic resonance scans. This study was presented at the 2012 NCDEU meeting in Phoenix, AZ. NR 45 TC 3 Z9 3 U1 4 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP 30 PY 2013 VL 213 IS 3 BP 217 EP 224 DI 10.1016/j.pscychresns.2013.05.008 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 211TV UT WOS:000323934800006 PM 23845563 ER PT J AU Wang, Y Lomakin, A Latypov, RF Laubach, JP Hideshima, T Richardson, PG Munshi, NC Anderson, KC Benedek, GB AF Wang, Ying Lomakin, Aleksey Latypov, Ramil F. Laubach, Jacob P. Hideshima, Teru Richardson, Paul G. Munshi, Nikhil C. Anderson, Kenneth C. Benedek, George B. TI Phase transitions in human IgG solutions SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PROTEIN CRYSTAL NUCLEATION; GAMMA-D-CRYSTALLIN; MONOCLONAL-ANTIBODIES; POLYETHYLENE-GLYCOL; LYSOZYME SOLUTIONS; AQUEOUS-SOLUTIONS; MULTIPLE-MYELOMA; SEPARATION; BEHAVIOR; MODEL AB Protein condensations, such as crystallization, liquid-liquid phase separation, aggregation, and gelation, have been observed in concentrated antibody solutions under various solution conditions. While most IgG antibodies are quite soluble, a few outliers can undergo condensation under physiological conditions. Condensation of IgGs can cause serious consequences in some human diseases and in biopharmaceutical formulations. The phase transitions underlying protein condensations in concentrated IgG solutions is also of fundamental interest for the understanding of the phase behavior of non-spherical protein molecules. Due to the high solubility of generic IgGs, the phase behavior of IgG solutions has not yet been well studied. In this work, we present an experimental approach to study IgG solutions in which the phase transitions are hidden below the freezing point of the solution. Using this method, we have investigated liquid-liquid phase separation of six human myeloma IgGs and two recombinant pharmaceutical human IgGs. We have also studied the relation between crystallization and liquid-liquid phase separation of two human cryoglobulin IgGs. Our experimental results reveal several important features of the generic phase behavior of IgG solutions: (1) the shape of the coexistence curve is similar for all IgGs but quite different from that of quasi-spherical proteins; (2) all IgGs have critical points located at roughly the same protein concentration at similar to 100 mg/ml while their critical temperatures vary significantly; and (3) the liquid-liquid phase separation in IgG solutions is metastable with respect to crystallization. These features of phase behavior of IgG solutions reflect the fact that all IgGs have nearly identical molecular geometry but quite diverse net inter-protein interaction energies. This work provides a foundation for further experimental and theoretical studies of the phase behavior of generic IgGs as well as outliers with large propensity to condense. The investigation of the phase diagram of IgG solutions is of great importance for the understanding of immunoglobulin deposition diseases as well as for the understanding of the colloidal stability of IgG pharmaceutical formulations. (C) 2013 AIP Publishing LLC. C1 [Wang, Ying; Lomakin, Aleksey; Benedek, George B.] MIT, Ctr Mat Proc, Cambridge, MA 02139 USA. [Latypov, Ramil F.] Amgen Inc, Proc & Prod Dev, Seattle, WA 98119 USA. [Laubach, Jacob P.; Hideshima, Teru; Richardson, Paul G.; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Dept Med Oncol, Boston, MA 02215 USA. [Benedek, George B.] MIT, Dept Phys, Cambridge, MA 02139 USA. [Benedek, George B.] MIT, Ctr Mat Sci & Engn, Cambridge, MA 02139 USA. RP Benedek, GB (reprint author), MIT, Ctr Mat Proc, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM gbb@mit.edu FU MIT FX We acknowledge Amgen Inc. for providing us pharmaceutical IgGs. We thank Onofrio Annunziata (Texas Christian University) and Neer Asherie (Yeshiva University) for helpful discussions. This study was supported by funds from the Alfred H. Caspary Professorship of Professor George Benedek (MIT). NR 54 TC 26 Z9 26 U1 4 U2 32 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 28 PY 2013 VL 139 IS 12 AR 121904 DI 10.1063/1.4811345 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 231DA UT WOS:000325392000007 PM 24089716 ER PT J AU Feinstein, TN Yui, N Webber, MJ Wehbi, VL Stevenson, HP King, JD Hallows, KR Brown, D Bouley, R Vilardaga, JP AF Feinstein, Timothy N. Yui, Naofumi Webber, Matthew J. Wehbi, Vanessa L. Stevenson, Hilary P. King, J. Darwin, Jr. Hallows, Kenneth R. Brown, Dennis Bouley, Richard Vilardaga, Jean-Pierre TI Noncanonical Control of Vasopressin Receptor Type 2 Signaling by Retromer and Arrestin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PARATHYROID-HORMONE RECEPTOR; RENAL EPITHELIAL-CELLS; COLLECTING DUCT; BETA-ARRESTINS; PROTEIN-KINASE; PTH RECEPTOR; ENDOCYTOSIS; KIDNEY; WATER; AQUAPORIN-2 AB The vasopressin type 2 receptor (V2R) is a critical G protein-coupled receptor (GPCR) for vertebrate physiology, including the balance of water and sodium ions. It is unclear how its two native hormones, vasopressin (VP) and oxytocin (OT), both stimulate the same cAMP/PKA pathway yet produce divergent antinatriuretic and antidiuretic effects that are either strong (VP) or weak (OT). Here, we present a new mechanism that differentiates the action of VP and OT on V2R signaling. We found that vasopressin, as opposed to OT, continued to generate cAMP and promote PKA activation for prolonged periods after ligand washout and receptor internalization in endosomes. Contrary to the classical model of arrestin-mediated GPCR desensitization, arrestins bind the VP-V2R complex yet extend rather than shorten the generation of cAMP. Signaling is instead turned off by the endosomal retromer complex. We propose that this mechanism explains how VP sustains water and Na+ transport in renal collecting duct cells. Together with recent work on the parathyroid hormone receptor, these data support the existence of a novel "noncanonical" regulatory pathway for GPCR activation and response termination, via the sequential action of beta-arrestin and the retromer complex. C1 [Feinstein, Timothy N.; Wehbi, Vanessa L.; Stevenson, Hilary P.; Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Lab GPCR Biol, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Yui, Naofumi; Webber, Matthew J.; Brown, Dennis; Bouley, Richard] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Yui, Naofumi; Webber, Matthew J.; Brown, Dennis; Bouley, Richard] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Yui, Naofumi; Webber, Matthew J.; Brown, Dennis; Bouley, Richard] Harvard Univ, Sch Med, Boston, MA 02114 USA. [King, J. Darwin, Jr.; Hallows, Kenneth R.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Program Membrane Biol, 185 Cambridge St,CPZN 8218, Boston, MA 02114 USA. EM Bouley.Richard@mgh.harvard.edu; jpv@pitt.edu OI Webber, Matthew/0000-0003-1092-4410 FU National Institutes of Health [R01 DK087688, R01 DK38452, R01 DK96586, R01 DK075048, P30 DK079307]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43341]; Cystic Fibrosis Foundation [KING10F0] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 DK087688 (to J.-P. V.), R01 DK38452, and R01 DK96586 (to D. B.), R01 DK075048 (to K. R. H.), and P30 DK079307 (to the Pittsburgh Kidney Research Center). This work was also supported by Boston Area Diabetes and Endocrinology Research Center Grant DK57521, Center for the Study of Inflammatory Bowel Disease Grant DK43341, and Cystic Fibrosis Foundation Grant KING10F0 (to D. K.). NR 55 TC 38 Z9 38 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 27 PY 2013 VL 288 IS 39 BP 27849 EP 27860 DI 10.1074/jbc.M112.445098 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302OB UT WOS:000330612800013 PM 23935101 ER PT J AU Heinrichs, SC Leite-Morrisa, KA Rasmusson, AM Kaplan, GB AF Heinrichs, Stephen C. Leite-Morrisa, Kimberly A. Rasmusson, Ann M. Kaplan, Gary B. TI Repeated valproate treatment facilitates fear extinction under specific stimulus conditions SO NEUROSCIENCE LETTERS LA English DT Article DE Conditioned fear; Extinction learning; Histone deacetylase inhibitors; Valproate; Sodium butyrate; Mouse ID POSTTRAUMATIC-STRESS-DISORDER; HISTONE DEACETYLASE INHIBITOR; CONTROLLED-TRIAL; SODIUM-BUTYRATE; RECONSOLIDATION; DIVALPROEX; ACQUISITION; MECHANISMS; MOUSE AB Single dose treatment with histone deacetylase inhibitor (HDACi) agents has been shown to enhance extinction learning in rodent models under certain conditions. The present novel studies were designed to examine the effects of repeated HDACi treatment, with valproate or sodium butyrate, on the extinction of conditioned fear. In Experiments 1 and 2, short duration CS exposure (30 s) in combination with vehicle administration progressively attenuated conditioned fear responses over 40 or more sessions. This effective extinction training was not augmented by HDACi treatments. In Experiment 3, we used a long duration CS exposure (120 s) to weaken extinction training. With these extinction parameters, repeated valproate treatment substantially facilitated the acquisition and retention of fear extinction. Results of this study extend previous work suggesting that HDACi's have utility in augmenting the efficiency of fear extinction, although their apparent benefits are critically dependent upon specific parameters of extinction training. (C) 2013 Published by Elsevier Ireland Ltd. C1 [Heinrichs, Stephen C.; Leite-Morrisa, Kimberly A.; Rasmusson, Ann M.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Rasmusson, Ann M.; Kaplan, Gary B.] VA Boston Healthcare Syst, Mental Hlth Serv, Boston, MA 02130 USA. [Leite-Morrisa, Kimberly A.; Rasmusson, Ann M.; Kaplan, Gary B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Leite-Morrisa, Kimberly A.; Kaplan, Gary B.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA. RP Kaplan, GB (reprint author), VA Boston Healthcare Syst, 116A150 South Huntington Ave, Boston, MA 02130 USA. EM Gary.Kaplan@va.gov FU Department of Veterans Affairs FX This research was supported by a Rehabilitation Research & Development grant from the Department of Veterans Affairs to author Kaplan. Authors Kaplan, Leite-Morris, Rasmusson, and Heinrichs designed the study. Author Heinrichs collected the behavioral measures, performed the statistical analysis of results, and wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript. NR 21 TC 8 Z9 8 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 27 PY 2013 VL 552 BP 108 EP 113 DI 10.1016/j.neulet.2013.07.035 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 237YG UT WOS:000325907000022 PM 23916657 ER PT J AU Bourkiza, B Vurro, M Jeffries, A Pezaris, JS AF Bourkiza, Bechir Vurro, Milena Jeffries, Ailsa Pezaris, John S. TI Visual Acuity of Simulated Thalamic Visual Prostheses in Normally Sighted Humans SO PLOS ONE LA English DT Article ID ELECTRICAL-STIMULATION; ARTIFICIAL VISION; CORTEX; BLIND; MICROSTIMULATION; RECOGNITION; INFORMATION; PERCEPTION; BEHAVIOR; RETINA AB Simulation in normally sighted individuals is a crucial tool to evaluate the performance of potential visual prosthesis designs prior to human implantation of a device. Here, we investigated the effects of electrode count on visual acuity, learning rate and response time in 16 normally sighted subjects using a simulated thalamic visual prosthesis, providing the first performance reports for thalamic designs. A new letter recognition paradigm using a multiple-optotype two-alternative forced choice task was adapted from the Snellen eye chart, and specifically devised to be readily communicated to both human and non-human primate subjects. Validation of the method against a standard Snellen acuity test in 21 human subjects showed no significant differences between the two tests. The novel task was then used to address three questions about simulations of the center-weighted phosphene patterns typical of thalamic designs: What are the expected Snellen acuities for devices with varying numbers of contacts, do subjects display rapid adaptation to the new visual modality, and can response time in the task provide clues to the mechanisms of perception in low-resolution artificial vision? Population performance (hit rate) was significantly above chance when viewing Snellen 20/200 optotypes (Log MAR 1.0) with 370 phosphenes in the central 10 degrees of vision, ranging to Snellen 20/800 (Log MAR 1.6) with 25 central phosphenes. Furthermore, subjects demonstrated learning within the 1-2 hours of task experience indicating the potential for an effective rehabilitation and possibly better visual performance after a longer period of training. Response time differences suggest that direct letter perception occurred when hit rate was above 75%, whereas a slower strategy like feature-based pattern matching was used in conditions of lower relative resolution. As pattern matching can substantially boost effective acuity, these results suggest post-implant therapy should specifically address feature detection skills. C1 [Bourkiza, Bechir; Vurro, Milena; Jeffries, Ailsa; Pezaris, John S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Pezaris, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM pezaris.john@mgh.harvard.edu FU National Eye Institute [EY019679]; Institut d'Optique; Rappaport Foundation FX This research was performed with support from the National Eye Institute through grant EY019679 (BB, MV, AJ, JSP; http://www.nei.nih.gov), from Institut d'Optique (BB; http://www.institutoptique.fr), and from the Rappaport Foundation (JSP; http://www.rappaportfoundation.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 6 Z9 6 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 27 PY 2013 VL 8 IS 9 AR UNSP e73592 DI 10.1371/journal.pone.0073592 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228WY UT WOS:000325223900017 PM 24086286 ER PT J AU Lee, HS Schlereth, S Khandelwal, P Saban, DR AF Lee, Hyun Soo Schlereth, Simona Khandelwal, Payal Saban, Daniel R. TI Ocular Allergy Modulation to Hi-Dose Antigen Sensitization Is a Treg-Dependent Process SO PLOS ONE LA English DT Article ID REGULATORY T-CELLS; IN-VIVO; AIRWAY INFLAMMATION; MURINE MODEL; BALB/C MICE; ASTHMA; FOXP3; CONJUNCTIVITIS; RESOLUTION; DEPLETION AB A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 mu g) versus hi-dose (1000 mu g) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease. C1 [Saban, Daniel R.] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27705 USA. [Saban, Daniel R.] Duke Univ, Sch Med, Dept Immunol, Durham, NC USA. [Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA. RP Saban, DR (reprint author), Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27705 USA. EM daniel.saban@duke.edu FU National Institutes of Health [R01EY021798] FX This study was supported by the National Institutes of Health R01EY021798 (Saban DR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 8 Z9 9 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 27 PY 2013 VL 8 IS 9 AR UNSP e75769 DI 10.1371/journal.pone.0075769 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228WY UT WOS:000325223900062 PM 24086630 ER PT J AU Rao, MN Blackwell, T Redline, S Punjabi, NM Barrett-Connor, E Neylan, TC Stone, KL AF Rao, Madhu N. Blackwell, Terri Redline, Susan Punjabi, Naresh M. Barrett-Connor, Elizabeth Neylan, Thomas C. Stone, Katie L. CA Osteoporotic Fractures Men MrOS St TI Association between Sleep Duration and 24-Hour Urine Free Cortisol in the MrOS Sleep Study SO PLOS ONE LA English DT Article ID SELF-REPORTED SLEEP; OSTEOPOROTIC FRACTURES; DEPRIVATION; ACTIGRAPHY; FREQUENCY; RELEASE; ADULTS; MEN AB Context: Short sleep duration is associated with adverse health outcomes, but the mechanisms involved are unknown. It has been postulated that short sleep duration may elevate cortisol levels, but studies have had conflicting results. It is unclear whether these differing findings may be due to methodological issues, such as assessment of sleep duration. Specifically, objective versus subjective methods of measuring habitual sleep duration may account for the conflicting results found in epidemiological studies. Objective: Our goal was to determine whether habitual sleep duration, measured objectively (by actigraphy) and subjectively (by self-report), was associated with 24-hour urine free cortisol (UFC), a measure of integrated cortisol secretion. Our secondary goal was to determine whether slow wave sleep (SWS, determined by polysomnography) was associated with 24-hour UFC. Design/Setting: Cross sectional study of community dwelling older men. Patients/Participants: 325 men (mean age = 76.6 years, SD = 5.5) from the Portland site of the MrOS Sleep Study, who underwent 24-hour urine collection, polysomnography, actigraphy and sleep questionnaire. Primary Outcome: 24-hour UFC. Results: In this study of community dwelling older men, self-reported sleep duration was inversely related to 24-hour UFC levels. Participants reporting <5 hours of habitual sleep had an adjusted mean 24-hour UFC of 29.8 ug, compared to 28.0 ug in participants reporting >5 to <8 hours of sleep 25.5 ug in those reporting >8 hours of habitual sleep. However, sleep duration determined by actigraphy was not associated with 24-hour UFC in either univariable or multivariable regression models. SWS was not associated with 24-hour UFC. Conclusion: Objectively measured (i.e., actigraphic) sleep duration is not associated with 24-hour UFC in these community dwelling older men. This finding, together with prior studies, suggests that elevated levels of integrated cortisol secretion is not the mechanisms by which short sleep duration leads to adverse health outcomes. C1 [Rao, Madhu N.] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. [Blackwell, Terri; Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Epidemiol, La Jolla, CA 92093 USA. [Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Rao, MN (reprint author), Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. EM Madhu.Rao@ucsf.edu FU National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA); National Cancer Institute (NCI); National Center for Research Resources (NCRR); NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; National Heart, Lung, and Blood Institute (NHLBI) [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, R01 HL070839]; NIH Heart, Lung and Blood Institute [K23HL096832] FX The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health 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 Cancer Institute (NCI), the National Center for Research Resources (NCRR) and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. Dr. Rao received funding from the NIH Heart, Lung and Blood Institute (K23HL096832), which also paid for measurement of 24-hour urine free cortisol. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 4 Z9 4 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 27 PY 2013 VL 8 IS 9 AR e75205 DI 10.1371/journal.pone.0075205 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228WY UT WOS:000325223900037 PM 24228086 ER PT J AU Yang, KS Budin, G Tassa, C Kister, O Weissleder, R AF Yang, Katherine S. Budin, Ghyslain Tassa, Carlos Kister, Olivier Weissleder, Ralph TI Bioorthogonal Approach to Identify Unsuspected Drug Targets in Live Cells SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE bioorthogonal reaction; proteins; proteomics; cleavable linkers; drug targets ID IN-VIVO; CHEMICAL PROTEOMICS; AMINO-ACIDS; POLY(ADP-RIBOSE) POLYMERASE; TOPOISOMERASE-II; SMALL MOLECULES; DNA-DAMAGE; KINASE; INHIBITORS; IDENTIFICATION C1 [Yang, Katherine S.; Budin, Ghyslain; Tassa, Carlos; Kister, Olivier; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health (NIH) [RO1CA164448, P50CA86355, T32-CA79443] FX This work was supported by the National Institutes of Health (NIH) grant number RO1CA164448 and P50CA86355, K. Y. was supported by an NIH grant T32-CA79443. NR 48 TC 12 Z9 12 U1 7 U2 55 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD SEP 27 PY 2013 VL 52 IS 40 BP 10593 EP 10597 DI 10.1002/anie.201304096 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 227EF UT WOS:000325091500042 PM 23960025 ER PT J AU Le, DE Pascotto, M Leong-Poi, H Sari, I Micari, A Kaul, S AF Le, D. Elizabeth Pascotto, Marco Leong-Poi, Howard Sari, Ibrahim Micari, Antonio Kaul, Sanjiv TI Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: comparison between carvedilol and metoprolol SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE Ischemic cardiomyopathy; Beta blockers; Regional flow; Regional function; Cytokines; Angiogenesis ID CHRONIC HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; HIBERNATING MYOCARDIUM; ADRENERGIC-BLOCKADE; LIPID-PEROXIDATION; OXIDATIVE STRESS; BLOOD-FLOW; INTERLEUKIN-1-BETA; EXERCISE AB There is controversy regarding the superiority of carvedilol (C) over metoprolol (M) in congestive heart failure. We hypothesized that C is superior to M in chronic ischemic cardiomyopathy because of its better anti-inflammatory and pro-angiogenic effects. In order to test our hypothesis we used a chronic canine model of multivessel ischemic cardiomyopathy where myocardial microcatheters were placed from which interstitial fluid was collected over time to measure leukocyte count and cytokine levels. After development of left ventricular dysfunction, the animals were randomized into four groups: sham (n = 7), placebo (n = 8), M (n = 11), and C (n = 10), and followed for 3 months after treatment initiation. Tissue was examined for immunohistochemistry, oxidative stress, and capillary density. At 3 months both rest and stress wall thickening were better in C compared to the other groups. At the end of 3 months of treatment end-systolic wall stress also decreased the most in C. Similarly resting myocardial blood flow (MBF) improved the most in C as did the stress endocardial/epicardial MBF. Myocardial interstitial fluid showed greater attenuation of leukocytosis with C compared to M, which was associated with less fibrosis and oxidative stress. C also had higher IL-10 level and capillary density. In conclusion, in a chronic canine model of multivessel ischemic cardiomyopathy we found 3 months of C treatment resulted in better resting global and regional function as well as better regional function at stress compared to M. These changes were associated with higher myocardial levels of the anti-inflammatory cytokine IL-10 and less myocardial oxidative stress, leukocytosis, and fibrosis. Capillary density and MBF were almost normalized. Thus in the doses used in this study, C appears to be superior to M in a chronic canine model of ischemic cardiomyopathy from beneficial effects on inflammation and angiogenesis. Further studies are required for comparing additional doses of these drugs. C1 [Le, D. Elizabeth] Portland VA Med Ctr, Portland, OR USA. [Le, D. Elizabeth] Knight Cardiovasc Inst, Portland, OR USA. [Le, D. Elizabeth; Kaul, Sanjiv] OHSU, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Pascotto, Marco] Buon Consiglio Fatebenefratelli Hosp, I-80123 Naples, Italy. [Leong-Poi, Howard] Heart & Stroke Fdn Canada, Ottawa, ON, Canada. [Leong-Poi, Howard] Canadian Inst Hlth Res, Ottawa, ON, Canada. [Sari, Ibrahim] Turkish Cardiac Soc, Istanbul, Turkey. [Micari, Antonio] Aventis Fdn, Italian Soc Cardiol, Milan, Italy. RP Kaul, S (reprint author), OHSU, Knight Cardiovasc Inst, UHN62,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM kauls@ohsu.edu FU National Institutes of Health [K-08-HL0742901, R01-HL660346] FX Supported in part by grants from the National Institutes of Health (K-08-HL0742901, D. Elizabeth Le and R01-HL660346, Sanjiv Kaul). The radiolabeled microspheres were provided by Dupont Pharmaceuticals, North Billerica, MA, and the ultrasound equipment was supplied by Philips Ultrasound, Andover, MA. NR 42 TC 14 Z9 16 U1 0 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD SEP 27 PY 2013 VL 108 IS 6 AR 384 DI 10.1007/s00395-013-0384-7 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 226IL UT WOS:000325028700001 PM 24072434 ER PT J AU Sarosiek, KA Chi, XK Bachman, JA Sims, JJ Montero, J Patel, L Flanagan, A Andrews, DW Sorger, P Letai, A AF Sarosiek, Kristopher A. Chi, Xiaoke Bachman, John A. Sims, Joshua J. Montero, Joan Patel, Luv Flanagan, Annabelle Andrews, David W. Sorger, Peter Letai, Anthony TI BID Preferentially Activates BAK while BIM Preferentially Activates BAX, Affecting Chemotherapy Response SO MOLECULAR CELL LA English DT Article ID CYTOCHROME-C RELEASE; PROGRAMMED CELL-DEATH; MYC-INDUCED APOPTOSIS; BCL-2 FAMILY-MEMBERS; DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; MITOCHONDRIAL APOPTOSIS; DEFICIENT MICE; ANIMAL DEVELOPMENT; OLIGOMERIZES BAK AB Apoptosis is a highly regulated form of cell death that controls normal homeostasis as well as the antitumor activity of many chemotherapeutic agents. Commitment to death via the mitochondrial apoptotic pathway requires activation of the mitochondrial pore-forming proteins BAK or BAX. Activation can be effected by the activator BH3-only proteins BID or BIM, which have been considered to be functionally redundant in this role. Herein, we show that significant activation preferences exist between these proteins: BID preferentially activates BAK while BIM preferentially activates BAX. Furthermore, we find that cells lacking BAK are relatively resistant to agents that require BID activation for maximal induction of apoptosis, including topoisomerase inhibitors and TRAIL. Consequently, patients with tumors that harbor a loss of BAK1 exhibit an inferior response to topoisomerase inhibitor treatment in the clinic. Therefore, BID and BIM have nonoverlapping roles in the induction of apoptosis via BAK and BAX, affecting chemotherapy response. C1 [Sarosiek, Kristopher A.; Montero, Joan; Patel, Luv; Flanagan, Annabelle; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sarosiek, Kristopher A.; Montero, Joan; Patel, Luv; Letai, Anthony] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chi, Xiaoke; Andrews, David W.] McMaster Univ, Dept Chem & Chem Biol, Hamilton, ON L8N 3Z5, Canada. [Bachman, John A.; Sims, Joshua J.; Sorger, Peter] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM anthony_letai@dfci.harvard.edu OI Andrews, David/0000-0002-9266-7157; Bachman, John/0000-0001-6095-2466 FU American Cancer Society [121360-PF-11-256-01-TBG]; Women's Cancers Program at the Dana-Farber Cancer Institute; NIH [RO1CA129974, P01CA139980] FX We kindly thank Dr. John C. Reed for providing us with the pcDNA3-myc-BAK plasmid. We gratefully acknowledge funding from the American Cancer Society Postdoctoral Fellowship 121360-PF-11-256-01-TBG (K.A.S.), Women's Cancers Program at the Dana-Farber Cancer Institute (K.A.S.), and NIH grants RO1CA129974 and P01CA139980. A.L. is a Leukemia and Lymphoma Society Scholar. NR 60 TC 62 Z9 65 U1 3 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD SEP 26 PY 2013 VL 51 IS 6 BP 751 EP 765 DI 10.1016/j.molcel.2013.08.048 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 296NG UT WOS:000330191200006 PM 24074954 ER PT J AU Qiao, Q Yang, CH Zheng, C Fontan, L David, L Yu, X Bracken, C Rosen, M Melnick, A Egelman, EH Wu, H AF Qiao, Qi Yang, Chenghua Zheng, Chao Fontan, Lorena David, Liron Yu, Xiong Bracken, Clay Rosen, Monica Melnick, Ari Egelman, Edward H. Wu, Hao TI Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation-Induced Filamentous Assembly SO MOLECULAR CELL LA English DT Article ID NF-KAPPA-B; MALT1 PROTEASE ACTIVITY; PARACASPASE MALT1; CRYSTAL-STRUCTURE; CARD11 MUTATIONS; CELL LYMPHOMA; ABC-DLBCL; ACTIVATION; COMPLEX; DEATH AB The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-kappa B signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to caspases. Here we show that the reconstituted CBM signalosome is a helical filamentous assembly in which substoichiometric CARMA1 nucleates Bcl10 filaments. Bcl10 filament formation is a highly cooperative process whose threshold is sensitized by oligomerized CARMA1 upon receptor activation. In cells, both cotransfected CARMA1/Bcl10 complex and the endogenous CBM signalosome are filamentous morphologically. Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10. Structure-guided mutagenesis confirmed the observed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-kB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization. C1 [Qiao, Qi; David, Liron; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Qiao, Qi; David, Liron; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yang, Chenghua; Zheng, Chao; Bracken, Clay; Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA. [Fontan, Lorena; Rosen, Monica; Melnick, Ari] Weill Cornell Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY 10021 USA. [Fontan, Lorena; Rosen, Monica; Melnick, Ari] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Yu, Xiong; Egelman, Edward H.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. RP Wu, H (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM hao.wu@childrens.harvard.edu OI Egelman, Edward/0000-0003-4844-5212 FU National Institutes of Health [R01AI089882, R01EB001567]; Cancer Research Institute; Spanish Ministry of Science and Innovation; Michael D. Ditzian Research Fund-Lymphoma Research Foundation FX We thank Natacha Opalka, Seth Darst, Leona Cohen-Gould, and Maria Ericsson for help with EM imaging, and Liwei Wang, Ermelinda Damko, and Qiubai Li for technical assistance, and recognize support from the National Institutes of Health (R01AI089882 to H. W. and R01EB001567 to E. H. E.), Cancer Research Institute (Q.Q., CY., and L.D.), Spanish Ministry of Science and Innovation (L.F.), and Michael D. Ditzian Research Fund-Lymphoma Research Foundation (L.F.). NR 34 TC 49 Z9 50 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD SEP 26 PY 2013 VL 51 IS 6 BP 766 EP 779 DI 10.1016/j.molcel.2013.08.032 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 296NG UT WOS:000330191200007 PM 24074955 ER PT J AU Kibengo, FM Ruzagira, E Katende, D Bwanika, AN Bahemuka, U Haberer, JE Bangsberg, DR Barin, B Rooney, JF Mark, D Chetty, P Fast, P Kamali, A Priddy, FH AF Kibengo, Freddie M. Ruzagira, Eugene Katende, David Bwanika, Agnes N. Bahemuka, Ubaldo Haberer, Jessica E. Bangsberg, David R. Barin, Burc Rooney, James F. Mark, David Chetty, Paramesh Fast, Patricia Kamali, Anatoli Priddy, Frances H. TI Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships: A Randomized, Clinical Trial SO PLOS ONE LA English DT Article ID ANTIRETROVIRAL THERAPY ADHERENCE; SELF-REPORT; INFECTION; PREVENTION; WOMEN; TRANSMISSION; BEHAVIOR; COUPLES; AFRICA; RISK AB Background: Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2: 1: 2: 1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-gamma ELISPOT. Results: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. C1 [Kibengo, Freddie M.; Ruzagira, Eugene; Katende, David; Bwanika, Agnes N.; Bahemuka, Ubaldo; Kamali, Anatoli] Med Res Council MRC Uganda Virus Res Inst UVRI Ug, Entebbe, Uganda. [Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Barin, Burc] EMMES Corp, Rockville, MD USA. [Rooney, James F.] Gilead Sci Inc, Foster City, CA 94404 USA. [Mark, David] Int AIDS Vaccine Initiat, Nairobi, Kenya. [Chetty, Paramesh] Int AIDS Vaccine Initiat, Johannesburg, South Africa. [Fast, Patricia; Priddy, Frances H.] Int AIDS Vaccine Initiat, New York, NY USA. RP Priddy, FH (reprint author), Int AIDS Vaccine Initiat, New York, NY USA. EM fpriddy@iavi.org FU International AIDS Vaccine Initiative FX The study was funded by the International AIDS Vaccine Initiative (www.iavi.org) with support in form of study medication (both active drug and placebo) provided by Gilead Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 23 Z9 24 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 26 PY 2013 VL 8 IS 9 AR e74314 DI 10.1371/journal.pone.0074314 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228VP UT WOS:000325220000008 PM 24086333 ER PT J AU Chakravarti, A Clark, AG Mootha, VK AF Chakravarti, Aravinda Clark, Andrew G. Mootha, Vamsi K. TI Distilling Pathophysiology from Complex Disease Genetics SO CELL LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ENVIRONMENT INTERACTION; HIRSCHSPRUNG-DISEASE; TRAITS; PATHOGENICITY; CHOLESTEROL; MUTATIONS; MEDICINE; NETWORK; COMMON AB Technologies for genome-wide sequence interrogation have dramatically improved our ability to identify loci associated with complex human disease. However, a chasm remains between correlations and causality that stems, in part, from a limiting theoretical framework derived from Mendelian genetics and an incomplete understanding of disease physiology. Here we propose a set of criteria, akin to Koch's postulates for infectious disease, for assigning causality between genetic variants and human disease phenotypes. C1 [Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Clark, Andrew G.] Cornell Univ, Ithaca, NY 14850 USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. EM aravinda@jhmi.edu FU NHLBI NIH HHS [R01 HL072904] NR 35 TC 34 Z9 34 U1 5 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 26 PY 2013 VL 155 IS 1 BP 21 EP 26 DI 10.1016/j.cell.2013.09.001 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 224UX UT WOS:000324916700006 PM 24074858 ER PT J AU Lappalainen, T Sammeth, M Friedlander, MR 't Hoen, PAC Monlong, J Rivas, MA Gonzalez-Porta, M Kurbatova, N Griebel, T Ferreira, PG Barann, M Wieland, T Greger, L van Iterson, M Almlof, J Ribeca, P Pulyakhina, I Esser, D Giger, T Tikhonov, A Sultan, M Bertier, G MacArthur, DG Lek, M Lizano, E Buermans, HPJ Padioleau, I Schwarzmayr, T Karlberg, O Ongen, H Kilpinen, H Beltran, S Gut, M Kahlem, K Amstislavskiy, V Stegle, O Pirinen, M Montgomery, SB Donnelly, P McCarthy, MI Flicek, P Strom, TM Lehrach, H Schreiber, S Sudbrak, R Carracedo, A Antonarakis, SE Haesler, R Syvaenen, AC Van Ommen, GJ Brazma, A Meitinger, T Rosenstiel, P Guigo, R Gut, IG Estivill, X Dermitzakis, ET AF Lappalainen, Tuuli Sammeth, Michael Friedlaender, Marc R. 't Hoen, Peter A. C. Monlong, Jean Rivas, Manuel A. Gonzalez-Porta, Mar Kurbatova, Natalja Griebel, Thasso Ferreira, Pedro G. Barann, Matthias Wieland, Thomas Greger, Liliana van Iterson, Maarten Almloef, Jonas Ribeca, Paolo Pulyakhina, Irina Esser, Daniela Giger, Thomas Tikhonov, Andrew Sultan, Marc Bertier, Gabrielle MacArthur, Daniel G. Lek, Monkol Lizano, Esther Buermans, Henk P. J. Padioleau, Ismael Schwarzmayr, Thomas Karlberg, Olof Ongen, Halit Kilpinen, Helena Beltran, Sergi Gut, Marta Kahlem, Katja Amstislavskiy, Vyacheslav Stegle, Oliver Pirinen, Matti Montgomery, Stephen B. Donnelly, Peter McCarthy, Mark I. Flicek, Paul Strom, Tim M. Lehrach, Hans Schreiber, Stefan Sudbrak, Ralf Carracedo, Angel Antonarakis, Stylianos E. Haesler, Robert Syvaenen, Ann-Christine Van Ommen, Gert-Jan Brazma, Alvis Meitinger, Thomas Rosenstiel, Philip Guigo, Roderic Gut, Ivo G. Estivill, Xavier Dermitzakis, Emmanouil T. CA Geuvadis Consortium TI Transcriptome and genome sequencing uncovers functional variation in humans SO NATURE LA English DT Article ID HUMAN GENE-EXPRESSION; POPULATION; LANDSCAPE; VARIANTS; QTLS AB Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome. C1 [Lappalainen, Tuuli; Giger, Thomas; Padioleau, Ismael; Ongen, Halit; Kilpinen, Helena; Montgomery, Stephen B.; Antonarakis, Stylianos E.; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli; Padioleau, Ismael; Ongen, Halit; Kilpinen, Helena; Antonarakis, Stylianos E.; Dermitzakis, Emmanouil T.] Univ Geneva, iG3, CH-1211 Geneva, Switzerland. [Lappalainen, Tuuli; Padioleau, Ismael; Ongen, Halit; Kilpinen, Helena; Dermitzakis, Emmanouil T.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Sammeth, Michael; Griebel, Thasso; Ribeca, Paolo; Beltran, Sergi; Gut, Marta; Kahlem, Katja; Gut, Ivo G.] Ctr Nacl Anal Genom, Barcelona 08028, Catalonia, Spain. [Sammeth, Michael; Friedlaender, Marc R.; Monlong, Jean; Ferreira, Pedro G.; Bertier, Gabrielle; Lizano, Esther; Guigo, Roderic; Estivill, Xavier] CRG, Barcelona 08003, Catalonia, Spain. [Sammeth, Michael; Friedlaender, Marc R.; Monlong, Jean; Ferreira, Pedro G.; Bertier, Gabrielle; Lizano, Esther; Guigo, Roderic; Estivill, Xavier] UPF, Barcelona 08003, Catalonia, Spain. [Sammeth, Michael; Friedlaender, Marc R.; Monlong, Jean; Ferreira, Pedro G.; Lizano, Esther; Guigo, Roderic; Estivill, Xavier] CRG Hosp del Mar Res Inst, Barcelona 08003, Catalonia, Spain. [Friedlaender, Marc R.; Lizano, Esther; Estivill, Xavier] CRG CIBERESP, Barcelona 08003, Catalonia, Spain. ['t Hoen, Peter A. C.; van Iterson, Maarten; Pulyakhina, Irina; Buermans, Henk P. J.; Van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands. [Rivas, Manuel A.; Pirinen, Matti; Donnelly, Peter; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Gonzalez-Porta, Mar; Kurbatova, Natalja; Greger, Liliana; Tikhonov, Andrew; Stegle, Oliver; Flicek, Paul; Brazma, Alvis] EBI, EMBL, Hinxton CB10 1SD, England. [Barann, Matthias; Esser, Daniela; Schreiber, Stefan; Haesler, Robert; Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany. [Wieland, Thomas; Schwarzmayr, Thomas; Strom, Tim M.; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Almloef, Jonas; Karlberg, Olof; Syvaenen, Ann-Christine] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, S-75185 Uppsala, Sweden. [Sultan, Marc; Amstislavskiy, Vyacheslav; Lehrach, Hans; Sudbrak, Ralf] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [MacArthur, Daniel G.; Lek, Monkol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [MacArthur, Daniel G.; Lek, Monkol] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Buermans, Henk P. J.] Leiden Genome Technol Ctr, NL-2300 RC Leiden, Netherlands. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7BN, England. [Strom, Tim M.; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany. [Lehrach, Hans; Sudbrak, Ralf] Dahlem Ctr Genome Res & Med Syst Biol, D-14195 Berlin, Germany. [Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Genom Med Grp, Fdn Publ Galega Med Xen SERGAS, Santiago De Compostela, Spain. [Meitinger, Thomas] Deutsch Forschungszentrum Herz Kreislauferkrankun, Partner Site Munich Heart Alliance, D-81675 Munich, Germany. RP Lappalainen, T (reprint author), Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. EM tuuli.e.lappalainen@gmail.com; emmanouil.dermitzakis@unige.ch RI Veltman, Joris/F-5128-2010; Beltran, Sergi/I-3408-2015; Meitinger, Thomas/O-1318-2015; Hasler, Robert/A-4908-2009; Almlof, Jonas/E-1608-2017; Ferreira, Pedro/J-6379-2013; Sammeth, Michael/C-1157-2014; Schreiber, Stefan/B-6748-2008; Estivill, Xavier/A-3125-2013; Antonarakis, Stylianos/N-8866-2014; Guigo, Roderic/D-1303-2010 OI Rosenstiel, Philip/0000-0002-9692-8828; Flicek, Paul/0000-0002-3897-7955; Monlong, Jean/0000-0002-9737-5516; Pirinen, Matti/0000-0002-1664-1350; Brazma, Alvis/0000-0001-5988-7409; Kilpinen-Barrett, Leena Helena/0000-0001-6692-6154; Lizano, Esther/0000-0003-3304-9807; Stegle, Oliver/0000-0002-8818-7193; Lappalainen, Tuuli/0000-0002-7746-8109; Gonzalez-Porta, Mar/0000-0002-1661-7254; Kurbatova, Natalja/0000-0002-3973-2909; Bertier, Gabrielle/0000-0002-3319-3721; Carracedo, Angel/0000-0003-1085-8986; Veltman, Joris/0000-0002-3218-8250; Beltran, Sergi/0000-0002-2810-3445; Almlof, Jonas/0000-0002-1211-9821; Friedlander, Marc/0000-0001-6577-4363; Ferreira, Pedro/0000-0003-3838-8664; Sammeth, Michael/0000-0002-6528-9883; Schreiber, Stefan/0000-0003-2254-7771; Estivill, Xavier/0000-0002-0723-2256; Antonarakis, Stylianos/0000-0001-8907-5823; Guigo, Roderic/0000-0002-5738-4477 FU European Commission [261123]; Swiss National Science Foundation [130326, 130342, 127375, 144082]; Louis Jeantet Foundation; ERC [260927, 294653, 249968]; NIH-NIMH [MH090941]; Spanish Plan Nacional (NOVADIS) [SAF2008-00357]; Generalitat de Catalunya AGAUR [2009 SGR-1502]; Instituto de Salud Carlos III (FIS/FEDER) [PI11/00733, PS09/02368]; Spanish Plan Nacional [BIO2011-26205]; ESGI; READNA [2008-201418]; Spanish Ministry of Economy and Competitiveness (MINECO); Generalitat de Catalunya; DFG Cluster of Excellence Inflammation at Interfaces; INTERREG4A project HIT-ID; BMBF IHEC project DEEP [SP 2.3]; German Centre for Cardiovascular Research (DZHK); German Ministry of Education and Research [01GR0802, 01GM0867, 01GR0804, 16EX1020C]; EurocanPlatform [FP7 260791]; ENGAGE [HEALTH-F4-2007-201413]; CAGEKID [241669]; Centre for Medical Systems Biology; Swedish Research Council [C0524801, A028001]; Knut and Alice Wallenberg Foundation [2011.0073]; German Federal Ministry of Education and Research [01GS08201]; Max Planck Society; Wellcome Trust [WT085532, 081917, 090367, 090532, 098381, 076113, 083270]; European Molecular Biology Laboratory; Medical Research Council UK [G0601261]; Wellcome Trust Centre for Human Genetics [090532/Z/09/Z, 075491/Z/04/B]; WTCCC2 project [085475/B/08/Z, 085475/Z/08/Z]; Royal Society Wolfson Merit Award; Wellcome Trust Senior Investigator Award [095552/Z/11/Z]; EMBO long-term fellowship EMBO-ALTF [2010-337]; NIH-NIGMS [R01 GM104371]; Marie Curie; Clarendon Fund of the University of Oxford; Nuffield Department of Medicine; EMBO long-term fellowship [ALTF225-2011]; Emil Aaltonen Foundation; Academy of Finland FX We would like to thank E. Falconnet, L. Romano, A. Planchon, D. Bielsen, A. Yurovsky, A. Buil, J. Bryois, A. Nica, I. Topolsky, N. Fusi, S. Waszak, C. Bustamante, J. Rung, N. Kolesnikov, A. Roa, E. Bragin, S. Brent, J. Gonzalez, M. Morell, A. Puig, E. Palumbo, M. Ventayol Garcia, J. F. J. Laros, J. Blanc, R. Birkelund, G. Plaja, M. Ingham, J. Camps, M. Bayes, L. Agueda, A. Gouin, M.-L. Yaspo, E. Graf, A. Walther, C. Fischer, S. Loesecke, B. Schmick, D. Balzereit, S. Dokel, M. Linser, A. Kovacsovics, M. Friskovec, C. von der Lancken, M. Schlapkohl, A. Hellmann, M. Schilhabel, the SNP&SEQ Technology Platform in Uppsala, S. Sauer, the Vital-IT high-performance computing centre of the SIB Swiss Institute of Bioinformatics, B. Goldstein and others at the Coriell Institute, and J. Cooper, E. Burnett, K. Ball and others at the European Collection of Cell Cultures (ECACC) and the 1000 Genomes Consortium. This project was funded by the European Commission 7th Framework Program (FP7) (261123; GEUVADIS); the Swiss National Science Foundation (130326, 130342), the Louis Jeantet Foundation, and ERC (260927) (E. T. D.); NIH-NIMH (MH090941) (E. T. D., M. I. M., R. G.); Spanish Plan Nacional SAF2008-00357 (NOVADIS), the Generalitat de Catalunya AGAUR 2009 SGR-1502, and the Instituto de Salud Carlos III (FIS/FEDER PI11/00733) (X. E.); Spanish Plan Nacional (BIO2011-26205) and ERC (294653) (R. G.); ESGI, READNA (FP7 Health-F4-2008-201418), Spanish Ministry of Economy and Competitiveness (MINECO) and the Generalitat de Catalunya (I. G. G.); DFG Cluster of Excellence Inflammation at Interfaces, the INTERREG4A project HIT-ID, and the BMBF IHEC project DEEP SP 2.3 (P.Ro.); German Centre for Cardiovascular Research (DZHK) and the German Ministry of Education and Research (01GR0802, 01GM0867, 01GR0804, 16EX1020C) (T. M.); EurocanPlatform (FP7 260791), ENGAGE and CAGEKID (241669) (A. B.); FP7/2007-2013, ENGAGE project, HEALTH-F4-2007-201413, and the Centre for Medical Systems Biology within the framework of The Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific and Research (NWO) (P. AC. H and G.-J.v.O.); The Swedish Research Council (C0524801, A028001) and the Knut and Alice Wallenberg Foundation (2011.0073) (A.-C. S.); The Swiss National Science Foundation (127375, 144082) and ERC (249968) (S. E. A.); Instituto de Salud Carlos III (FIS/FEDER PS09/02368) (A. C.); German Federal Ministry of Education and Research (01GS08201) (R. S.); Max Planck Society (H. L.); Wellcome Trust (WT085532) and the European Molecular Biology Laboratory (P. F.); ENGAGE, Wellcome Trust (081917, 090367, 090532, 098381), and Medical Research Council UK (G0601261) (M. I. M.); Wellcome Trust Centre for Human Genetics (090532/Z/09/Z, 075491/Z/04/B), Wellcome Trust (098381, 090367, 076113, 083270), the WTCCC2 project (085475/B/08/Z, 085475/Z/08/Z), Royal Society Wolfson Merit Award, Wellcome Trust Senior Investigator Award (095552/Z/11/Z) (P. D.); EMBO long-term fellowship EMBO-ALTF 2010-337 (H. K.); NIH-NIGMS (R01 GM104371) (D. G. M.); Marie Curie FP7 fellowship (O.S.); Scholarship by the Clarendon Fund of the University of Oxford, and the Nuffield Department of Medicine (M. A. R.); EMBO long-term fellowship ALTF225-2011 (M. R. F.); Emil Aaltonen Foundation and Academy of Finland fellowships (T.L.). NR 35 TC 403 Z9 405 U1 19 U2 110 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 26 PY 2013 VL 501 IS 7468 BP 506 EP 511 DI 10.1038/nature12531 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223RP UT WOS:000324826300049 PM 24037378 ER PT J AU Marty, FM Winston, DJ Rowley, SD Vance, E Papanicolaou, GA Mullane, KM Brundage, TM Robertson, AT Godkin, S Mommeja-Marin, H Boeckh, M AF Marty, Francisco M. Winston, Drew J. Rowley, Scott D. Vance, Estil Papanicolaou, Genovefa A. Mullane, Kathleen M. Brundage, Thomas M. Robertson, Alice T. Godkin, Susan Mommeja-Marin, Herve Boeckh, Michael CA CMX001-201 Clinical Study Grp TI CMX001 to Prevent Cytomegalovirus Disease in Hematopoietic-Cell Transplantation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REPLICATION IN-VITRO; ACYCLIC NUCLEOSIDE PHOSPHONATES; POLYOMAVIRUS BK REPLICATION; LIPID-ESTER PRODRUGS; ANTIVIRAL ACTIVITY; CYCLIC CIDOFOVIR; GANCICLOVIR PROPHYLAXIS; ALKOXYALKYL ESTERS; MARROW TRANSPLANT; VIRUS-INFECTIONS AB BackgroundThe use of available antiviral agents for the prevention of cytomegalovirus (CMV) disease is limited by frequent toxic effects and the emergence of resistance. CMX001 has potent in vitro activity against CMV and other double-stranded DNA viruses. We evaluated the safety and anti-CMV activity of CMX001 in patients who had undergone allogeneic hematopoietic-cell transplantation. MethodsFrom December 2009 through June 2011, a total of 230 patients with data that could be evaluated were enrolled in the study. We randomly assigned these adult CMV-seropositive transplant recipients from 27 centers to oral administration of CMX001 or placebo. Patients were assigned in a 3:1 ratio to five sequential study cohorts according to a dose-escalating, double-blind design. Randomization was stratified according to the presence or absence of acute graft-versus-host disease and CMV DNA in plasma. Patients received the study drug after engraftment for 9 to 11 weeks, until week 13 after transplantation. Polymerase-chain-reaction analysis of CMV DNA in plasma was performed weekly. Patients in whom CMV DNA was detected at a level that required treatment discontinued the study drug and received preemptive treatment against CMV infection. The primary end point was a CMV event, defined as CMV disease or a plasma CMV DNA level greater than 200 copies per milliliter when the study drug was discontinued. The analysis was conducted in the intention-to-treat population. ResultsThe incidence of CMV events was significantly lower among patients who received CMX001 at a dose of 100 mg twice weekly than among patients who received placebo (10% vs. 37%; risk difference, -27 percentage points; 95% confidence interval, -42 to -12; P=0.002). Diarrhea was the most common adverse event in patients receiving CMX001 at doses of 200 mg weekly or higher and was dose-limiting at 200 mg twice weekly. Myelosuppression and nephrotoxicity were not observed. ConclusionsTreatment with oral CMX001 at a dose of 100 mg twice weekly significantly reduced the incidence of CMV events in recipients of hematopoietic-cell transplants. Diarrhea was dose-limiting in this population at a dose of 200 mg twice weekly. (Funded by Chimerix; CMX001-201 ClinicalTrials.gov number, NCT00942305.) A dose-finding study showed that CMX001 at an oral dose of 100 mg twice weekly, as compared with placebo, reduced the risk of cytomegalovirus events from 37% to 10% among patients who had undergone hematopoietic-cell transplantation. Cytomegalovirus (CMV) infection is a common cause of illness after allogeneic hematopoietic-cell transplantation.(1),(2) CMV seropositivity in transplant recipients is also associated with an increased risk of death after transplantation, despite preemptive and prophylactic strategies with available antiviral agents.(3)-(5) Although valganciclovir is approved for prophylaxis against CMV infection after solid-organ transplantation, its use is limited by myelosuppression, particularly after hematopoietic-cell transplantation.(3),(6)-(8) Thus, there is an unmet need for effective drugs against CMV infection that have a better safety profile. CMX001 is an orally bioavailable lipid acyclic nucleoside phosphonate that is absorbed in the small intestine and transported ... C1 [Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marty, Francisco M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Winston, Drew J.] Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. [Rowley, Scott D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Vance, Estil] Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Papanicolaou, Genovefa A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mullane, Kathleen M.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Brundage, Thomas M.; Robertson, Alice T.; Godkin, Susan; Mommeja-Marin, Herve] Chimerix, Durham, NC USA. [Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Marty, FM (reprint author), Dana Farber Canc Inst, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM fmarty@partners.org OI Papanicolaou, Genovefa/0000-0002-2891-079X FU Chimerix FX Supported by Chimerix. NR 34 TC 124 Z9 128 U1 1 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 26 PY 2013 VL 369 IS 13 BP 1227 EP 1236 DI 10.1056/NEJMoa1303688 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 224LT UT WOS:000324888200009 PM 24066743 ER PT J AU Cho, TA Schmahmann, JD Cunnane, ME AF Cho, Tracey A. Schmahmann, Jeremy D. Cunnane, Mary E. TI Case 30-2013: A 19-Year-Old Man with Otalgia, Slurred Speech, and Ataxia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EPSTEIN-BARR-VIRUS; ACUTE CEREBELLAR-ATAXIA; COGNITIVE-AFFECTIVE SYNDROME; INFECTION; CHILDREN; BRAIN; ENCEPHALITIS C1 [Cho, Tracey A.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cunnane, Mary E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cho, Tracey A.; Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Cunnane, Mary E.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Cho, TA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU WorldCare Clinical; Oncolytics Biotech FX Dr. Cunnane reports receiving payment from WorldCare Clinical for image interpretation for a drug trial sponsored by Oncolytics Biotech. No other potential conflict of interest relevant to this article was reported. NR 39 TC 4 Z9 4 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 26 PY 2013 VL 369 IS 13 BP 1253 EP 1261 DI 10.1056/NEJMcpc1214218 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 224LT UT WOS:000324888200013 PM 24066747 ER PT J AU Nakada, Y Stewart, TG Pena, CG Zhang, S Zhao, N Bardeesy, N Sharpless, NE Wong, KK Hayes, DN Castrillon, DH AF Nakada, Yuji Stewart, Thomas G. Pena, Christopher G. Zhang, Song Zhao, Ni Bardeesy, Nabeel Sharpless, Norman E. Wong, Kwok-Kin Hayes, D. Neil Castrillon, Diego H. TI The LKB1 Tumor Suppressor as a Biomarker in Mouse and Human Tissues SO PLOS ONE LA English DT Article ID LUNG-CANCER; GROWTH-CONTROL; EXPRESSION; DIFFERENTIATION; INACTIVATION; LKB1/STK11; MELANOMA; GENE AB Germline mutations in the LKB1 gene (also known as STK11) cause the Peutz-Jeghers Syndrome, and somatic loss of LKB1 has emerged as causal event in a wide range of human malignancies, including melanoma, lung cancer, and cervical cancer. The LKB1 protein is a serine-threonine kinase that phosphorylates AMP-activated protein kinase (AMPK) and other downstream targets. Conditional knockout studies in mouse models have consistently shown that LKB1 loss promotes a highly-metastatic phenotype in diverse tissues, and human studies have demonstrated a strong association between LKB1 inactivation and tumor recurrence. Furthermore, LKB1 deficiency confers sensitivity to distinct classes of anticancer drugs. The ability to reliably identify LKB1-deficient tumors is thus likely to have important prognostic and predictive implications. Previous research studies have employed polyclonal antibodies with limited success, and there is no widely-employed immunohistochemical assay for LKB1. Here we report an assay based on a rabbit monoclonal antibody that can reliably detect endogenous LKB1 protein (and its absence) in mouse and human formalin-fixed, paraffin-embedded tissues. LKB1 protein levels determined through this assay correlated strongly with AMPK phosphorylation both in mouse and human tumors, and with mRNA levels in human tumors. Our studies fully validate this immunohistochemical assay for LKB1 in paraffin-embedded formalin tissue sections. This assay should be broadly useful for research studies employing mouse models and also for the development of human tissue-based assays for LKB1 in diverse clinical settings. C1 [Nakada, Yuji; Pena, Christopher G.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Nakada, Yuji; Pena, Christopher G.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75390 USA. [Stewart, Thomas G.; Zhao, Ni; Sharpless, Norman E.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. [Stewart, Thomas G.; Zhao, Ni; Sharpless, Norman E.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Stewart, Thomas G.; Zhao, Ni; Sharpless, Norman E.; Hayes, D. Neil] Univ N Carolina, Chapel Hill, NC 27599 USA. [Zhang, Song] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA USA. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hayes, DN (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. EM hayes@med.unc.edu; diego.castrillon@utsouthwestern.edu RI Zhao, Ni/P-9086-2014; OI Zhao, Ni/0000-0002-7762-3949; wong, kwok kin/0000-0001-6323-235X FU National Institutes of Health/National Cancer Institute [R01CA137181, RO1CA163896, U01CA141576]; Cancer Prevention Research Institute of Texas [RP100550] FX This study was supported through National Institutes of Health/National Cancer Institute grants R01CA137181 (DC), RO1CA163896 (NS, KW), U01CA141576 (DC, KW, NB, NS), and Cancer Prevention Research Institute of Texas grant RP100550 (DC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 8 Z9 8 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 25 PY 2013 VL 8 IS 9 AR e73449 DI 10.1371/journal.pone.0073449 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 228VC UT WOS:000325218700009 PM 24086281 ER PT J AU Bowling, CB Sharma, P Fox, CS O'Hare, AM Muntner, P AF Bowling, C. Barrett Sharma, Pradeep Fox, Caroline S. O'Hare, Ann M. Muntner, Paul TI Prevalence of Reduced Estimated Glomerular Filtration Rate Among the Oldest Old From 1988-1994 Through 2005-2010 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CHRONIC KIDNEY-DISEASE; AGE C1 [Bowling, C. Barrett] Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Atlanta, GA 30033 USA. [Sharma, Pradeep; Muntner, Paul] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA. [Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [O'Hare, Ann M.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. RP Bowling, CB (reprint author), Atlanta Vet Affairs Med Ctr, 1670 Clairmont Rd 11B, Decatur, GA 30033 USA. EM cbbowli@emory.edu FU CSRD VA [IK2 CX000856]; NHLBI NIH HHS [Y1-HC-8039]; NIA NIH HHS [R03 AG042336, R03AG042336-01] NR 6 TC 12 Z9 12 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 25 PY 2013 VL 310 IS 12 BP 1284 EP 1286 DI 10.1001/jama.2013.252441 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 222SO UT WOS:000324751800026 PM 24065016 ER PT J AU Baek, JH Eisner, LR Nierenberg, AA AF Baek, Ji Hyun Eisner, Lori R. Nierenberg, Andrew A. TI Smoking and suicidality in subjects with major depressive disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Suicide; Smoking; Epidemiologic database ID CIGARETTE-SMOKING; ANXIETY DISORDERS; BIPOLAR DISORDER; PERSONALITY-DISORDERS; NICOTINE DEPENDENCE; UNITED-STATES; RISK-FACTORS; COMORBIDITY; SYMPTOMS; MOOD AB Background: Detailed characteristics of depressive smokers and its association with suicidality were still less investigated. The aim of this study was to delineate characteristics of smokers with major depressive disorder (MDD) and examine the relationship between these characteristics and suicidality using an epidemiologic database, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Methods: A total of 5695 subjects with MDD, defined by the DSM-IV criteria, were included in our analysis. Current smokers, former smokers, and lifetime nonsmokers were compared in terms of demographic, clinical characteristics, and functional level. Suicidality, evaluated by history of suicide ideation and attempts while in a low mood was evaluated and compared among the groups. Results: Current smokers with MDD showed a greater number of DSM-IV symptoms while in acute episodes, a higher rate of alcohol and drug-use disorders, and poorer functional levels than nonsmokers. Previous smokers displayed intermediate characteristics between current smokers and nonsmokers. The logistic regression analysis revealed that both current and former smoking status predicted the risk of having a history of attempted suicide (current smokers: odds ratio 1.62, 95% Cl, 1.42-1.86; former smokers: odds ratio 1.37, 95% Cl. 1.13-1.66) after adjusting for demographic data, a history of subthreshold hypomania, and a lifetime axis II/anxiety/alcohol use/substance-use disorder. Limitations: Retrospective, cross-sectional evaluation; suicidality assessed only in the most severe depressive episode. Conclusions: The present study corroborates that smokers with MDD showed distinct clinical characteristics, and cigarette smoking can predict attempted suicide in a community representative sample of people with MDD. (C) 2013 Elsevier B.V. All rights reserved C1 [Baek, Ji Hyun; Eisner, Lori R.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Baek, Ji Hyun; Eisner, Lori R.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Eisner, Lori R.; Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Bipolar Clin, 50 Staniford St,Ste 580, Boston, MA 02114 USA. EM anierenberg@partners.org FU MGH from NIMH; AHRQ Forest Research Institute; PamLabs; Pfizer Pharmaceuticals; Shire; Astra Zeneca; Eli Lilly; Janssen Pharmaceuticals FX Health, Shire, Schering-Plough, Targacept, and Takeda/Lundbeck Pharmaceuticals. He received grant/research support through MGH from NIMH, AHRQ Forest Research Institute, PamLabs, Pfizer Pharmaceuticals, Shire; received honoraria from Belvoir Publishing, University of Texas Southwestern Dallas, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, CRICO, Dartmouth Medical School, IMEDEX, Israel Society for Biological Psychiatry, Johns Hopkins University, MJ Consulting, New York State, Medscape, MBL Publishing, National Association of Continuing Education, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, University of Pisa, University of Michigan, University of Miami, APSARD, ISBD, SciMed, Slack Publishing, Wolters Klower Publishing: is a presenter for the Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA were supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: Astra Zeneca, Eli Lilly, and Janssen Pharmaceuticals; in 2009 Astra Zeneca, Eli Lilly, and BristolMyers Squibb: (was) on the advisory boards of Appliance Computing, Inc., Brain Cells, Inc., Eli Lilly and Company, Johnson and Johnson, Takeda/Lundbeck, Targacept, InfoMedic; owns stock options in Appliance Computing, Inc. and Brain Cells, Inc; through MGH, Dr. Nierenberg is named for copyrights to: the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for The American Journal of Psychiatry Page 2 of 18Peer Review Onlythe Montgomery Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). Also, through MGH, Dr. Nierenberg has a patent extension application for the combination of buspirone, bupropion, and melatonin for the treatment of depression. NR 40 TC 10 Z9 10 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP 25 PY 2013 VL 150 IS 3 BP 1158 EP 1166 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 213ER UT WOS:000324038000065 PM 23827531 ER PT J AU Grottkau, BE Yang, XM Zhang, L Ye, L Lin, YF AF Grottkau, Brian E. Yang, Xingmei Zhang, Liang Ye, Ling Lin, Yunfeng TI Comparison of Effects of Mechanical Stretching on Osteogenic Potential of ASCs and BMSCs SO BONE RESEARCH LA English DT Article DE mechanotransduction; stem cells; osteoblasts; adipocytes ID MARROW STROMAL CELLS; MESENCHYMAL STEM-CELLS; HUMAN ADIPOSE-TISSUE; MULTI-LINEAGE CELLS; BONE-MARROW; IN-VITRO; DIFFERENTIATION; ADIPOGENESIS; PROLIFERATION; MOBILIZATION AB Mechanical forces play critical roles in the development and remodeling processes of bone. As an alternative cell source for bone engineering, adipose-derived stem cells (ASCs) should be fully investigated for their responses to mechanical stress. Similarly, the osteogenic potential, stimulated by mechanical stress, should be compared with bone marrow stromal cells (BMSCs), which have been clinically used for bone tissue engineering. In this study, ASCs and BMSCs were osteogenic-induced for 48 hours, and then subjected to uniaxial mechanical stretching for 2 or 6 hours. Cell orientation, osteogenic regulatory genes, osteogenic genes and ALP activities were measured and compared between ASCs and BMSCs. ASCs could align in a perpendicular way to the direction of stretching stress, while BMSCs did not present a specific alignment. Both 2 and 6 hours mechanical stretching could enhance the mRNA expression of Osx and Runx2 in BMSCs and ASCs, while OCN mRNA only increased in ASCs after 6 hours mechanical loading. Mechanical stretching enhanced the BMP-2 mRNA expression in ASCs, while only after 6 hours of mechanical loading significantly increased the BMP-2 gene expression in BMSCs. Significant differences only exist between ASCs and BMSCs loaded at 2 hours of mechanical stretching. It is concluded that ASCs are more rapid responders to mechanical stress, and have greater potential than BMSCs in osteogenesis when stimulated by mechanical stretching, indicating their usefulness for bone study in a rat model. C1 [Grottkau, Brian E.; Lin, Yunfeng] Harvard Univ, MassGen Hosp Children, Sch Med, Dept Orthopaed Surg, Boston, MA 02138 USA. [Grottkau, Brian E.; Lin, Yunfeng] Harvard Univ, Sch Med, Pediat Orthopaed Lab Tissue Engn & Regenerat Med, Boston, MA USA. [Yang, Xingmei; Zhang, Liang; Ye, Ling; Lin, Yunfeng] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. RP Lin, YF (reprint author), Harvard Univ, MassGen Hosp Children, Sch Med, Dept Orthopaed Surg, Boston, MA 02138 USA. EM yunfenglin@scu.edu.cn RI Lin, Yunfeng/M-5438-2013 OI Lin, Yunfeng/0000-0003-1224-6561 FU Peabody Foundation, Inc.; Constance and Anthony A Franchi Fund for Pediatric Orthopaedics at the MassGeneral Hospital for Children; National Natural Science Foundation of China [81071273, 31170929, 81200810] FX This work was funded by the Peabody Foundation, Inc., the Constance and Anthony A Franchi Fund for Pediatric Orthopaedics at the MassGeneral Hospital for Children, and National Natural Science Foundation of China (81071273, 31170929, 81200810). NR 32 TC 17 Z9 18 U1 3 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2095-4700 EI 2095-6231 J9 BONE RES JI Bone Res. PD SEP 25 PY 2013 VL 1 BP 282 EP 290 DI 10.4248/BR201303006 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA AT5OQ UT WOS:000344992500004 PM 26273508 ER PT J AU Stern, RA Daneshvar, DH Baugh, CM Seichepine, DR Montenigro, PH Riley, DO Fritts, NG Stamm, JM Robbins, CA McHale, L Simkin, I Stein, TD Alvarez, VE Goldstein, LE Budson, AE Kowall, NW Nowinski, CJ Cantu, RC McKee, AC AF Stern, Robert A. Daneshvar, Daniel H. Baugh, Christine M. Seichepine, Daniel R. Montenigro, Philip H. Riley, David O. Fritts, Nathan G. Stamm, Julie M. Robbins, Clifford A. McHale, Lisa Simkin, Irene Stein, Thor D. Alvarez, Victor E. Goldstein, Lee E. Budson, Andrew E. Kowall, Neil W. Nowinski, Christopher J. Cantu, Robert C. McKee, Ann C. TI Clinical presentation of chronic traumatic encephalopathy SO NEUROLOGY LA English DT Article ID BRAIN-INJURY; ALZHEIMERS-DISEASE; HEAD-INJURY; FRONTOTEMPORAL DEMENTIA; FOOTBALL; APOLIPOPROTEIN-EPSILON-4; NEUROPATHOLOGY; ASSOCIATION; CONCUSSION; DIAGNOSIS AB Objective: The goal of this study was to examine the clinical presentation of chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases. Methods: Thirty-six adult male subjects were selected from all cases of neuropathologically confirmed CTE at the Boston University Center for the Study of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no comorbid neurodegenerative or motor neuron disease, and had next-of-kin informants to provide retrospective reports of the subjects' histories and clinical presentations. These interviews were conducted blind to the subjects' neuropathologic findings. Results: A triad of cognitive, behavioral, and mood impairments was common overall, with cognitive deficits reported for almost all subjects. Three subjects were asymptomatic at the time of death. Consistent with earlier case reports of boxers, 2 relatively distinct clinical presentations emerged, with one group whose initial features developed at a younger age and involved behavioral and/or mood disturbance (n = 22), and another group whose initial presentation developed at an older age and involved cognitive impairment (n = 11). Conclusions: This suggests there are 2 major clinical presentations of CTE, one a behavior/mood variant and the other a cognitive variant. C1 [Stern, Robert A.; Daneshvar, Daniel H.; Baugh, Christine M.; Seichepine, Daniel R.; Montenigro, Philip H.; Riley, David O.; Fritts, Nathan G.; Stamm, Julie M.; Robbins, Clifford A.; Stein, Thor D.; Alvarez, Victor E.; Nowinski, Christopher J.; Cantu, Robert C.; McKee, Ann C.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02215 USA. [Stern, Robert A.; Stein, Thor D.; Goldstein, Lee E.; Budson, Andrew E.; Kowall, Neil W.; McKee, Ann C.] Boston Univ, Sch Med, BU Alzheimers Dis Ctr, Boston, MA 02215 USA. [Stern, Robert A.; Baugh, Christine M.; Seichepine, Daniel R.; Alvarez, Victor E.; Budson, Andrew E.; Kowall, Neil W.; McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Stern, Robert A.; Cantu, Robert C.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02215 USA. [Stein, Thor D.; Kowall, Neil W.; McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Simkin, Irene] Boston Univ, Sch Med, Mol Genet Core Facil, Boston, MA 02215 USA. [McHale, Lisa; Nowinski, Christopher J.; Cantu, Robert C.] Sports Legacy Inst, Waltham, MA USA. [Stein, Thor D.; Alvarez, Victor E.; Budson, Andrew E.; Kowall, Neil W.; McKee, Ann C.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02215 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Biomed Engn, Boston, MA 02215 USA. [Goldstein, Lee E.] Boston Univ, Sch Med, Dept Elect & Comp Engn, Boston, MA 02215 USA. RP Stern, RA (reprint author), Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02215 USA. EM bobstern@bu.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Montenigro, Philip/0000-0003-4442-9207 FU NIH [R01 NS078337, P30 AG13846]; Department of Veterans Affairs [CSP 501, B6796-C]; Sports Legacy Institute; National Operating Committee on Standards for Athletic Equipment FX Supported by NIH (R01 NS078337, P30 AG13846), Department of Veterans Affairs (CSP 501, B6796-C), Sports Legacy Institute, National Operating Committee on Standards for Athletic Equipment, and unrestricted gifts from the National Football League and the Andlinger Foundation. NR 39 TC 100 Z9 100 U1 6 U2 33 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 24 PY 2013 VL 81 IS 13 BP 1122 EP 1129 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EL UT WOS:000330768000010 PM 23966253 ER PT J AU Moscovitch-Lopatin, M Goodman, RE Eberly, S Ritch, JJ Rosas, HD Matson, S Matson, W Oakes, D Young, AB Shoulson, I Hersch, SM AF Moscovitch-Lopatin, Miriam Goodman, Rachel E. Eberly, Shirley Ritch, James J. Rosas, H. Diana Matson, Samantha Matson, Wayne Oakes, David Young, Anne B. Shoulson, Ira Hersch, Steven M. CA Huntington Study Grp PHAROS TI HTRF analysis of soluble huntingtin in PHAROS PBMCs SO NEUROLOGY LA English DT Article ID MUTANT HUNTINGTIN; DISEASE; BRAIN; ANTIBODIES; PROTEIN; MOUSE; LOCALIZATION; AGGREGATION; REPEAT AB Objective: We measured the levels of mutant huntingtin (mtHtt) and total huntingtin (tHtt) in blood leukocytes from Prospective Huntington At-Risk Observational Study (PHAROS) subjects at 50% risk of carrying the Huntington disease mutation using a homogeneous time-resolved fluorescence (HTRF) assay to assess its potential as a biomarker. Methods: Peripheral blood mononuclear cells from consenting PHAROS subjects were analyzed by HTRF using antibodies that simultaneously measured mtHtt and tHtt. mtHtt levels were normalized to tHtt, double-stranded DNA, or protein and analyzed according to cytosine-adenine-guanine repeat length (CAGn), demographics, predicted time to clinical onset or known time since clinical onset, and available clinical measures. Results: From 363 assayed samples, 342 met quality control standards. Levels of mtHtt andmt/tHtt were higher in 114 subjects with expanded CAG repeats (CAG >= 37) compared with 228 subjects with nonexpanded CAG repeats (CAG <37) (p < 0.0001). Analysis of relationships to predicted time to onset or to phenoconversion suggested that the HTRF signal could mark changes during the Huntington disease prodrome or after clinical onset. Conclusions: The HTRF assay can effectively measure mtHtt in multicenter sample sets and may be useful in trials of therapies targeting huntingtin. C1 [Moscovitch-Lopatin, Miriam; Goodman, Rachel E.; Ritch, James J.; Rosas, H. Diana; Matson, Samantha; Young, Anne B.; Hersch, Steven M.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Eberly, Shirley; Oakes, David] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Matson, Wayne] Vet Adm Hosp, Bedford, MA USA. [Shoulson, Ira] Georgetown Univ, Program Regulatory Sci & Med, Washington, DC USA. RP Hersch, SM (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. EM hersch@helix.mgh.harvard.edu FU NIH/National Institute of Neurological Disorders and Stroke [UO1NS071789, PO1NS058793]; NIH/National Human Genome Research Institute [HG02449-01]; High Q Foundation FX Supported by NIH/National Institute of Neurological Disorders and Stroke grants to S.M.H. (UO1NS071789 and PO1NS058793); PHAROS was supported by NIH/National Human Genome Research Institute (HG02449-01) and the High Q Foundation. The authors have declared that no financial interests exist. The 2B7-Tb antibody was made available to the authors by Novartis for purchase through Cisbio. NR 32 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 24 PY 2013 VL 81 IS 13 BP 1134 EP 1140 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EL UT WOS:000330768000012 PM 23966247 ER PT J AU Berg, AT Baca, CB Loddenkemper, T Vickrey, BG Dlugos, D AF Berg, Anne T. Baca, Christine B. Loddenkemper, Tobias Vickrey, Barbara G. Dlugos, Dennis TI Priorities in pediatric epilepsy research Improving children's futures today SO NEUROLOGY LA English DT Review ID QUALITY STANDARDS SUBCOMMITTEE; INFANTILE SPASMS; INTRACTABLE EPILEPSY; AMERICAN-ACADEMY; UNITED-STATES; PRACTICE PARAMETER; NEUROLOGY SOCIETY; ONSET EPILEPSY; TEMPORAL-LOBE; CARE AB The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of patient-centered and patient-driven mandates for developing best practices in care, particularly for epilepsy beginning under age 3 years. The workshop brought together parents, representatives of voluntary advocacy organizations, physicians, allied health professionals, researchers, and administrators to identify priority areas for pediatric epilepsy care and research including implementation and testing of interventions designed to improve care processes and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure control but also behavioral, academic, and social functioning; 2) early and accurate diagnosis and optimal treatment; 3) role and involvement of parents (communication and shared decision-making); and 4) integration of school and community organizations with epilepsy care delivery. Key factors influencing pediatric epilepsy care included the child's impairments and seizure presentation, parents, providers, the health care system, and community systems. Care was represented as a sequential process from initial onset of seizures to referral for comprehensive evaluation when needed. We considered an alternative model in which comprehensive care would be utilized from onset, proactively, rather than reactively after pharmacoresistance became obvious. Barriers, including limited levels of evidence about many aspects of diagnosis and management, access to care-particularly epilepsy specialty and behavioral health care-and implementation, were identified. Progress hinges on coordinated research efforts that systematically address gaps in knowledge and overcoming barriers to access and implementation. The stakes are considerable, and the potential benefits for reduced burden of refractory epilepsy and lifelong disabilities may be enormous. C1 [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Baca, Christine B.; Vickrey, Barbara G.] Epilepsy Ctr, Chicago, IL USA. [Baca, Christine B.; Vickrey, Barbara G.] Northwestern Mem Feinberg Sch Med, Dept Pediat, Chicago, IL USA. [Baca, Christine B.; Vickrey, Barbara G.] Calif State Univ Los Angeles, Dept Neurol, Los Angeles, CA 90032 USA. [Loddenkemper, Tobias] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Loddenkemper, Tobias] Div Epilepsy & Clin Neurophysiol, Los Angeles, CA USA. [Dlugos, Dennis] Harvard Univ, Sch Med, Dept Neurol, Boston Childrens Hosp, Boston, MA 02115 USA. [Dlugos, Dennis] Univ Penn, Pediat Reg Epilepsy Program, Philadelphia, PA 19104 USA. [Dlugos, Dennis] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Dlugos, Dennis] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. RP Berg, AT (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. EM atberg@luriechildrens.org FU Citizens United for Research on Epilepsy (CURE) FX Citizens United for Research on Epilepsy (CURE) provided funding for travel and accommodations for many of the speakers and participants and made possible the meeting summarized in this report. Additional support for the meeting was provided by the Foundation of Ann & Robert H. Lurie Children's Hospital of Chicago. NR 59 TC 14 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 24 PY 2013 VL 81 IS 13 BP 1166 EP 1175 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EL UT WOS:000330768000017 PM 23966254 ER PT J AU Chan, AT AF Chan, Andrew T. TI Aspirin for the Prevention of Colorectal Cancer SO PROGRESS IN CHEMISTRY LA English DT Article DE aspirin; colorectal cancer; randomized controlled trials; nonaspirin nonsteroidal anti-inflammatory drugs; chemoprevention ID RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE ASPIRIN; CARDIOVASCULAR-DISEASE; PHYSICIANS HEALTH; SURVIVAL AB Consistent experimental, epidemiologic, and recent randomized controlled trial evidence demonstrates that aspirin lowers the risk of colorectal cancer (CRC). Prior expert bodies have recommended against the routine use of aspirin to prevent CRC in individuals at average risk, particularly in view of potential adverse consequences, including gastrointestinal bleeding. However, such recommendations preceded more recent high quality evidence of the benefit of aspirin for the prevention of not only colorectal cancer, but other cancers as well. This review summarizes this compelling body of evidence supporting the chemopreventive efficacy of aspirin. A broad anti-cancer effect of aspirin coupled with its potential role in the prevention of cardiovascular disease may tip the balance in favor of chronic aspirin use for many patients. C1 Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM achan@partners.org NR 17 TC 2 Z9 3 U1 1 U2 11 PU CHINESE ACAD SCIENCES PI BEIJING PA NO. 33 BEISIHUANXILU, ZHONGGUANCUN, BEIJING 100080, PEOPLES R CHINA SN 1005-281X J9 PROG CHEM JI Prog. Chem. PD SEP 24 PY 2013 VL 25 IS 9 SI SI BP 1450 EP 1453 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 244TD UT WOS:000326412200005 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Patients with osteoarthritis and avascular necrosis have better functional outcomes and those with avascular necrosis worse pain outcomes compared to rheumatoid arthritis after primary hip arthroplasty: a cohort study SO BMC MEDICINE LA English DT Article DE Total hip replacement; Diagnosis; Osteoarthritis; Rheumatoid arthritis; Avascular necrosis; Pain; Function; Arthroplasty; Joint replacement; Patient-reported outcomes; Risk factors ID TOTAL JOINT ARTHROPLASTY; QUALITY-OF-LIFE; KNEE REPLACEMENT SURGERY; FOLLOW-UP; PREDICTORS; RESPONSIVENESS; QUESTIONNAIRE; RESPONSES; RATES; SCORE AB Background: This study was conducted to assess whether patient-reported outcomes (PROs) differ by the underlying diagnosis (rheumatoid arthritis (RA)/inflammatory arthritis, osteoarthritis (OA), avascular necrosis of bone (AVN), other) in patients undergoing primary total hip arthroplasty (THA). Methods: We used prospectively collected data to assess the association of diagnosis with index hip function and pain. Moderate-severe activity limitation and moderate-severe pain were assessed at two-and five-year follow-up after primary THA using multivariable-adjusted logistic regression analyses. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results: There were 5,707 primary THAs at two-years and 3,289 at five-years, 51% were women and the mean age was 65 years. The underlying diagnosis was RA in 3%, OA in 87%, AVN in 7% and other in 3%. In multivariable-adjusted analyses, compared to RA, diagnoses of OA and AVN were significantly associated with lower odds of moderate-severe activities of daily living limitations with an OR (95% CI) of 0.5 (0.3 to 0.8) (P = 0.01) and 0.4 (0.2 to 0.8) (P = 0.01), respectively, at two-years, but not at five-years, 0.7 (0.4 to 1.4) (P = 0.36) and 0.9 (0.4 to 1.8) (P = 0.78), respectively. At two-years, neither OA nor AVN were significantly associated with higher odds of moderate-severe pain (1.6 (0.6 to 4.5) (P = 0.40) and 2.8 (0.9 to 8.5) (P = 0 0.06)), respectively. At five-years, AVN was associated with higher odds of moderate-severe pain with OR 4.1 (1.2 to 14.1) (P = 0.02), but not OA, 2.1 (0.7 to 6.5) (P = 0.22). Conclusions: We found that patients with OA and AVN had better functional outcomes and those with AVN worse pain outcomes after primary THA, compared to patients with RA/inflammatory arthritis. Insights into mediators of these relationships are needed to better understand these associations. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Mayo Clinic Orthopedic Surgery research funds; National Institutes of Health (NIH) Clinical Translational Science Award [1 KL2 RR024151-01]; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institute of Aging (NIA); National Cancer Institute (NCI) FX This study was supported by research funds from the Mayo Clinic Orthopedic Surgery research funds, National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. JAS is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute of Aging (NIA) and National Cancer Institute (NCI). The funding agencies played no role in the design, collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. This study was presented as an oral abstract presentation at the 2012 American College of Rheumatology Annual meeting in Washington, DC in November 2012. NR 38 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD SEP 24 PY 2013 VL 11 AR 210 DI 10.1186/1741-7015-11-210 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 241PO UT WOS:000326179600001 PM 24063410 ER PT J AU Lewis, GD Bossone, E Naeije, R Grunig, E Saggar, R Lancellotti, P Ghio, S Varga, J Rajagopalan, S Oudiz, R Rubenfire, M AF Lewis, Gregory D. Bossone, Eduardo Naeije, Robert Gruenig, Ekkehard Saggar, Rajeev Lancellotti, Patrizio Ghio, Stefano Varga, Janos Rajagopalan, Sanjay Oudiz, Ronald Rubenfire, Melvyn TI Pulmonary Vascular Hemodynamic Response to Exercise in Cardiopulmonary Diseases SO CIRCULATION LA English DT Article DE exercise test; hemodynamics; hypertension; pulmonary; pulmonary circulation ID PRESERVED EJECTION FRACTION; CHRONIC HEART-FAILURE; VENTRICULAR SYSTOLIC FUNCTION; ARTERY PRESSURE RESPONSE; AORTIC-VALVE-REPLACEMENT; AIR-FLOW OBSTRUCTION; SYSTEMIC-SCLEROSIS; OF-CARDIOLOGY; PHOSPHODIESTERASE-5 INHIBITION; MITRAL REGURGITATION C1 [Lewis, Gregory D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bossone, Eduardo] IRCCS Policlin San Donato, Milan, Italy. [Naeije, Robert] Univ Libre Brussels, Brussels, Belgium. [Gruenig, Ekkehard] Univ Heidelberg Hosp, Heidelberg, Germany. [Saggar, Rajeev] St Joseph Hosp & Med Ctr, Phoenix, AZ USA. [Lancellotti, Patrizio] Univ Liege Hosp, GIGA Cardiovasc Sci, Liege, Belgium. [Ghio, Stefano] Fdn IRCCS Policlin S Matteo, Pavia, Italy. [Varga, Janos] Natl Koranyi Inst TB & Pulmonol, Budapest, Hungary. [Rajagopalan, Sanjay] Ohio State Univ, Columbus, OH 43210 USA. [Oudiz, Ronald] Univ Calif Los Angeles, David Geffen Sch Med, Torrance, CA USA. [Rubenfire, Melvyn] Univ Michigan, Ann Arbor, MI 48106 USA. RP Rubenfire, M (reprint author), Univ Michigan, 24 Frank Lloyd Wright Dr,Lobby A,Ste 3700, Ann Arbor, MI 48106 USA. EM mrubenfi@med.umich.edu NR 68 TC 87 Z9 89 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 24 PY 2013 VL 128 IS 13 BP 1470 EP 1479 DI 10.1161/CIRCULATIONAHA.112.000667 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223SZ UT WOS:000324831600019 PM 24060943 ER PT J AU Walsh, RM Hochedlinger, K AF Walsh, Ryan M. Hochedlinger, Konrad TI A variant CRISPR-Cas9 system adds versatility to genome engineering SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID CRISPR/CAS C1 [Walsh, Ryan M.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Regenerat Med, Ctr Canc, Boston, MA 02114 USA. [Walsh, Ryan M.; Hochedlinger, Konrad] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Walsh, Ryan M.; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Regenerat Med, Ctr Canc, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu FU Howard Hughes Medical Institute NR 11 TC 7 Z9 10 U1 4 U2 46 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 24 PY 2013 VL 110 IS 39 BP 15514 EP 15515 DI 10.1073/pnas.1314697110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 222XE UT WOS:000324765100015 PM 24014593 ER PT J AU Tsao, HW Tai, TS Tseng, W Chang, HH Grenningloh, R Miaw, SC Ho, IC AF Tsao, Hsiao-Wei Tai, Tzong-Shyuan Tseng, William Chang, Hui-Hsin Grenningloh, Roland Miaw, Shi-Chuen Ho, I-Cheng TI Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTIONAL REPRESSOR BLIMP-1; T-CELL HOMEOSTASIS; RECEPTOR; DIFFERENTIATION; EXPRESSION; ACTIVATION; FAMILY; PHOSPHORYLATION; ENHANCER; GENE AB E26 transformation-specific sequence 1 (Ets-1), the prototype of the ETS family of transcription factors, is critical for the expression of IL-2 by murine Th cells; however, its mechanism of action is still unclear. Here we show that Ets-1 is also essential for optimal production of IL-2 by primary human Th cells. Although Ets-1 negatively regulates the expression of Blimp1, a known suppressor of IL-2 expression, ablation of B lymphocyte-induced maturation protein 1 (Blimp1) does not rescue the expression of IL-2 by Ets-1-deficient Th cells. Instead, Ets-1 physically and functionally interacts with the nuclear factor of activated T-cells (NFAT) and is required for the recruitment of NFAT to the IL-2 promoter. In addition, Ets-1 is located in both the nucleus and cytoplasm of resting Th cells. Nuclear Ets-1 quickly exits the nucleus in response to calcium-dependent signals and competes with NFAT proteins for binding to protein components of noncoding RNA repressor of NFAT complex (NRON), which serves as a cytoplasmic trap for phosphorylated NFAT proteins. This nuclear exit of Ets-1 precedes rapid nuclear entry of NFAT and Ets-1 deficiency results in impaired nuclear entry, but not dephosphorylation, of NFAT proteins. Thus, Ets-1 promotes the expression of IL-2 by modulating the activity of NFAT. C1 [Tsao, Hsiao-Wei; Miaw, Shi-Chuen] Natl Taiwan Univ, Coll Med, Grad Inst Immunol, Taipei 10051, Taiwan. [Tai, Tzong-Shyuan; Tseng, William; Chang, Hui-Hsin; Grenningloh, Roland; Ho, I-Cheng] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Ho, I-Cheng] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ho, I-Cheng] VA Boston Healthcare Syst, Rheumatol Sect, Boston, MA 02130 USA. RP Miaw, SC (reprint author), Natl Taiwan Univ, Coll Med, Grad Inst Immunol, Taipei 10051, Taiwan. EM smiaw@ntu.edu.tw; iho@partners.org OI MIAW, SHI-CHUEN/0000-0003-1347-9367 FU National Institutes of Health [AI081052]; US Department of Defense [W81XWH-11-1-0492]; National Science Council of Taiwan [NSC 100-2320-B-002-090-MY3]; Graduate Students Study Abroad Program FX This work is supported by National Institutes of Health Grant AI081052 (to I.-C.H.), US Department of Defense Grant W81XWH-11-1-0492 (to I.-C. H.), National Science Council of Taiwan Grant NSC 100-2320-B-002-090-MY3 (to S.-C.M.), and Graduate Students Study Abroad Program (H.-W.T.). NR 27 TC 12 Z9 12 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 24 PY 2013 VL 110 IS 39 BP 15776 EP 15781 DI 10.1073/pnas.1304343110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 222XE UT WOS:000324765100060 PM 24019486 ER PT J AU Niederst, MJ Engelman, JA AF Niederst, Matthew J. Engelman, Jeffrey A. TI Bypass Mechanisms of Resistance to Receptor Tyrosine Kinase Inhibition in Lung Cancer SO SCIENCE SIGNALING LA English DT Review ID MUTANT COLORECTAL CANCERS; ACQUIRED-RESISTANCE; MET AMPLIFICATION; EGF RECEPTOR; GEFITINIB RESISTANCE; ACTIVATING MUTATIONS; THERAPY; CELLS; AXL; ERLOTINIB AB Receptor tyrosine kinases (RTKs) are activated by somatic genetic alterations in a subset of cancers, and such cancers are often sensitive to specific inhibitors of the activated kinase. Two well-established examples of this paradigm include lung cancers with either EGFR mutations or ALK translocations. In these cancers, inhibition of the corresponding RTK leads to suppression of key downstream signaling pathways, such as the PI3K (phosphatidylinositol 3-kinase)/AKT and MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathways, resulting in cell growth arrest and death. Despite the initial clinical efficacy of ALK (anaplastic lymphoma kinase) and EGFR (epidermal growth factor receptor) inhibitors in these cancers, resistance invariably develops, typically within 1 to 2 years. Over the past several years, multiple molecular mechanisms of resistance have been identified, and some common themes have emerged. One is the development of resistance mutations in the drug target that prevent the drug from effectively inhibiting the respective RTK. A second is activation of alternative RTKs that maintain the signaling of key downstream pathways despite sustained inhibition of the original drug target. Indeed, several different RTKs have been implicated in promoting resistance to EGFR and ALK inhibitors in both laboratory studies and patient samples. In this mini-review, we summarize the concepts underlying RTK-mediated resistance, the specific examples known to date, and the challenges of applying this knowledge to develop improved therapeutic strategies to prevent or overcome resistance. C1 [Niederst, Matthew J.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Niederst, Matthew J.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM jengelman@partners.org FU NIH/National Cancer Institute [R01CA137008]; Lung Cancer Research Foundation FX This work was supported by the NIH/National Cancer Institute (R01CA137008, J.A.E.) and the Lung Cancer Research Foundation (Scientific Merit Award, M.J.N.). NR 44 TC 68 Z9 68 U1 2 U2 36 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 J9 SCI SIGNAL JI Sci. Signal. PD SEP 24 PY 2013 VL 6 IS 294 AR re6 DI 10.1126/scisignal.2004652 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 224DT UT WOS:000324863000006 PM 24065147 ER PT J AU Dryden-Peterson, S Jayeoba, O Hughes, MD Jibril, H McIntosh, K Modise, TA Asmelash, A Powis, KM Essex, M Shapiro, RL Lockman, S AF Dryden-Peterson, Scott Jayeoba, Oluwemimo Hughes, Michael D. Jibril, Haruna McIntosh, Kenneth Modise, Taolo A. Asmelash, Aida Powis, Kathleen M. Essex, Max Shapiro, Roger L. Lockman, Shahin TI Cotrimoxazole Prophylaxis and Risk of Severe Anemia or Severe Neutropenia in HAART-Exposed, HIV-Uninfected Infants SO PLOS ONE LA English DT Article ID TO-CHILD TRANSMISSION; ANTIRETROVIRAL THERAPY; AFRICAN ADULTS; COTE-DIVOIRE; PREVENTION; ZIDOVUDINE; WOMEN; PREGNANCY; BOTSWANA; REGIMENS AB Background: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure-risk difference, -0.69% (95% confidence interval [CI] -2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI -1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1-6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. C1 [Dryden-Peterson, Scott; Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Dryden-Peterson, Scott; Jayeoba, Oluwemimo; Modise, Taolo A.; Asmelash, Aida; Powis, Kathleen M.; Essex, Max; Shapiro, Roger L.; Lockman, Shahin] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Dryden-Peterson, Scott; McIntosh, Kenneth; Powis, Kathleen M.; Essex, Max; Shapiro, Roger L.; Lockman, Shahin] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Jibril, Haruna] Minist Hlth, Dept Publ Hlth, Gaborone, Botswana. [McIntosh, Kenneth] Boston Childrens Hosp, Div Infect Dis, Boston, MA USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Dryden-Peterson, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. EM scott_peterson@post.harvard.edu FU Harvard University Center for AIDS Research (CFAR), a National Institutes of Health (NIH) [P30 AI060354]; NIH; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; MCCAM; FIC; OAR; Fogarty International Center [R24 TW007988]; Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene; Harvard Institute for Global Health FX Work supported by a research grant from the Harvard University Center for AIDS Research (CFAR), a National Institutes of Health (NIH)-funded program (P30 AI060354) which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, MCCAM, FIC, and OAR, and career development grants (to S. D. P) from the Fogarty International Center (R24 TW007988), Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene, and the Harvard Institute for Global Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 1 Z9 1 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 23 PY 2013 VL 8 IS 9 AR e74171 DI 10.1371/journal.pone.0074171 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246EK UT WOS:000326520200024 PM 24086319 ER PT J AU Zhang, LL Guo, S Schwab, JH Nielsen, GP Choy, E Ye, SN Zhang, Z Mankin, H Hornicek, FJ Duan, ZF AF Zhang, Linlin Guo, Shang Schwab, Joseph H. Nielsen, G. Petur Choy, Edwin Ye, Shunan Zhang, Zhan Mankin, Henry Hornicek, Francis J. Duan, Zhenfeng TI Tissue Microarray Immunohistochemical Detection of Brachyury Is Not a Prognostic Indicator in Chordoma SO PLOS ONE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR BRACHYURY; CANCER; TARGET; EXPRESSION; DIAGNOSIS; TUMOR; GENE AB Brachyury is a marker for notochord-derived tissues and neoplasms, such as chordoma. However, the prognostic relevance of brachyury expression in chordoma is still unknown. The improvement of tissue microarray technology has provided the opportunity to perform analyses of tumor tissues on a large scale in a uniform and consistent manner. This study was designed with the use of tissue microarray to determine the expression of brachyury. Brachyury expression in chordoma tissues from 78 chordoma patients was analyzed by immunohistochemical staining of tissue microarray. The clinicopathologic parameters, including gender, age, location of tumor and metastatic status were evaluated. Fifty-nine of 78 (75.64%) tumors showed nuclear staining for brachyury, and among them, 29 tumors (49.15%) showed 1+ (<= 30% positive cells) staining, 15 tumors (25.42%) had 2+ (31% to 60% positive cells) staining, and 15 tumors (25.42%) demonstrated 3+ (61% to 100% positive cells) staining. Brachyury nuclear staining was detected more frequently in sacral chordomas than in chordomas of the mobile spine. However, there was no significant relationship between brachyury expression and other clinical variables. By Kaplan-Meier analysis, brachyury expression failed to produce any significant relationship with the overall survival rate. In conclusion, brachyury expression is not a prognostic indicator in chordoma. C1 [Zhang, Linlin; Guo, Shang; Schwab, Joseph H.; Choy, Edwin; Ye, Shunan; Zhang, Zhan; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Zhang, Linlin; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Dept Pathol, Zhengzhou 450052, Peoples R China. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Guo, Shang] Shanghai Jiao Tong Univ, Dept Orthopaed, Shanghai Peoples Hosp 6, Shanghai 200030, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. EM zduan@partners.org FU Stephan L. Harris Fund; Jennifer Hunter Yates Foundation FX This project was supported by a grant from the Stephan L. Harris Fund and the Jennifer Hunter Yates Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 14 Z9 16 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 23 PY 2013 VL 8 IS 9 AR e75851 DI 10.1371/journal.pone.0075851 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246EK UT WOS:000326520200122 PM 24086644 ER PT J AU Zuniga, J Yu, N Barquera, R Alosco, S Ohashi, M Lebedeva, T Acuna-Alonzo, V Yunis, M Granados-Montiel, J Cruz-Lagunas, A Vargas-Alarcon, G Rodriguez-Reyna, TS Fernandez-Vina, M Granados, J Yunis, EJ AF Zuniga, Joaquin Yu, Neng Barquera, Rodrigo Alosco, Sharon Ohashi, Marina Lebedeva, Tatiana Acuna-Alonzo, Victor Yunis, Maria Granados-Montiel, Julio Cruz-Lagunas, Alfredo Vargas-Alarcon, Gilberto Rodriguez-Reyna, Tatiana S. Fernandez-Vina, Marcelo Granados, Julio Yunis, Edmond J. TI HLA Class I and Class II Conserved Extended Haplotypes and Their Fragments or Blocks in Mexicans: Implications for the Study of Genetic Diversity in Admixed Populations SO PLOS ONE LA English DT Article ID STR-PCR POLYMORPHISMS; ALLELE FREQUENCIES; AMERINDIAN POPULATIONS; B-ALLELES; EQUATORIAL-GUINEA; CABO-VERDE; C ALLELES; HUMAN MHC; LOCI; RESOLUTION AB Major histocompatibility complex (MHC) genes are highly polymorphic and informative in disease association, transplantation, and population genetics studies with particular importance in the understanding of human population diversity and evolution. The aim of this study was to describe the HLA diversity in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA-A, -B, -C), and class II (HLA-DRB1, -DQB1) genes using high-resolution sequence based typing (SBT) method and we structured the blocks and conserved extended haplotypes (CEHs) in 234 non-related admixed Mexican individuals (468 haplotypes) by a maximum likelihood method. We found that HLA blocks and CEHs are primarily from Amerindian and Caucasian origin, with smaller participation of African and recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in Mexicans from the central area of Mexico. We also analyzed the degree of admixture in this group using short tandem repeats (STRs) and HLA-B that correlated with the frequency of most probable ancestral HLA-C/-B and -DRB1/-DQB1 blocks and CEHs. Our results contribute to the analysis of the diversity and ancestral contribution of HLA class I and HLA class II alleles and haplotypes of Mexican admixed individuals from Mexico City. This work will help as a reference to improve future studies in Mexicans regarding allotransplantation, immune responses and disease associations. C1 [Zuniga, Joaquin; Cruz-Lagunas, Alfredo] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Immunol, Mexico City, DF, Mexico. [Yu, Neng; Alosco, Sharon; Ohashi, Marina; Lebedeva, Tatiana] Amer Red Cross, HLA Lab, Northeast Div, Dedham, MA USA. [Barquera, Rodrigo; Acuna-Alonzo, Victor] Natl Sch Anthropol & Hist, Mol Genet Lab, Mexico City, DF, Mexico. [Yunis, Maria; Yunis, Edmond J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Granados-Montiel, Julio] Inst Nacl Rehabil, Tissue Engn Cell Therapy & Regenerat Med Res Unit, Mexico City, DF, Mexico. [Vargas-Alarcon, Gilberto] Inst Nacl Cardiol Ignacio Chavez, Lab Genom, Mexico City, DF, Mexico. [Rodriguez-Reyna, Tatiana S.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico. [Fernandez-Vina, Marcelo] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Granados, Julio] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Transplantat, Mexico City, DF, Mexico. RP Granados, J (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Transplantat, Mexico City, DF, Mexico. EM julgrate@yahoo.com; Edmond_yunis@dfci.harvard.edu OI CRUZ-LAGUNAS, ALFREDO/0000-0001-5487-5919 NR 87 TC 17 Z9 18 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 23 PY 2013 VL 8 IS 9 AR e74442 DI 10.1371/journal.pone.0074442 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246EK UT WOS:000326520200031 PM 24086347 ER PT J AU Glat, M Skaat, H Menkes-Caspi, N Margel, S Stern, EA AF Glat, Micaela Skaat, Hadas Menkes-Caspi, Noa Margel, Shlomo Stern, Edward A. TI Age-dependent effects of microglial inhibition in vivo on Alzheimer's disease neuropathology using bioactive-conjugated iron oxide nanoparticles SO JOURNAL OF NANOBIOTECHNOLOGY LA English DT Article DE Tau; Microglia; Tangle; Fibrin gamma(377-395) peptide; Iron oxide nanoparticles ID CONVECTION-ENHANCED DELIVERY; TAU-PROTEIN; MAGHEMITE NANOPARTICLES; MOUSE MODEL; NEUROFIBRILLARY TANGLES; PATHOLOGY; CELLS; PHOSPHORYLATION; ACTIVATION; CLEARANCE AB Background: Tau dysfunction is believed to be the primary cause of neurodegenerative disorders referred to as tauopathies, including Alzheimer's disease, Pick's disease, frontotemporal dementia and Parkinsonism. The role of microglial cells in the pathogenesis of tauopathies is still unclear. The activation of microglial cells has been correlated with neuroprotective effects through the release of neurotrophic factors and through clearance of cell debris and phagocytosis of cells with intracellular inclusions. In contrast, microglial activation has also been linked with chronic neuroinflammation contributing to the development of neurodegenerative diseases such as tauopathies. Microglial activation has been recently reported to precede tangle formation and the attenuation of tau pathology occurs after immunosuppression of transgenic mice. Methods: Here we report the specific inhibition of microglial cells in rTg4510 tau-mutant mice by using fibrin gamma(377-395) peptide conjugated to iron oxide (gamma-Fe2O3) nanoparticles of 21 +/- 3.5 nm diameter. Results: Stabilization of the peptide by its covalent conjugation to the gamma-Fe2O3 nanoparticles significantly decreased the number of the microglial cells compared to the same concentration of the free peptide. The specific microglial inhibition induces different effects on tau pathology in an age dependent manner. The reduction of activation of microglial cells at an early age increases the number of neurons with hyperphosphorylated tau in transgenic mice. In contrast, reduction of activation of microglial cells reduced the severity of the tau pathology in older mice. The number of neurons with hyperphosphorylated tau and the number of neurons with tangles are reduced than those in animals not receiving the fibrin gamma(377-395) peptide-nanoparticle conjugate. Conclusions: These results demonstrate a differential effect of microglial activity on tau pathology using the fibrin gamma(377-395) peptide-nanoparticle conjugate, depending on age and/or stage of the neuropathological accumulation and aggregation. C1 [Glat, Micaela; Menkes-Caspi, Noa; Stern, Edward A.] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. [Skaat, Hadas; Margel, Shlomo] Bar Ilan Inst Nanotechnol & Adv Mat, Dept Chem, IL-52900 Ramat Gan, Israel. [Stern, Edward A.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Stern, Edward A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Stern, EA (reprint author), Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. EM sterned@mail.biu.ac.il OI Glat, Micaela Johanna/0000-0001-8332-1667 FU Elias, Genevieve and Georgianna Atol Charitable Trust FX This work was supported by the Elias, Genevieve and Georgianna Atol Charitable Trust. NR 53 TC 5 Z9 5 U1 3 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-3155 J9 J NANOBIOTECHNOL JI J. Nanobiotechnol. PD SEP 23 PY 2013 VL 11 AR 32 DI 10.1186/1477-3155-11-32 PG 12 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 233BB UT WOS:000325538100002 PM 24059692 ER PT J AU Baer, HJ Karson, AS Soukup, JR Williams, DH Bates, DW AF Baer, Heather J. Karson, Andrew S. Soukup, Jane R. Williams, Deborah H. Bates, David W. TI Documentation and Diagnosis of Overweight and Obesity in Electronic Health Records of Adult Primary Care Patients SO JAMA INTERNAL MEDICINE LA English DT Letter ID BODY-MASS INDEX; TRENDS C1 [Baer, Heather J.; Soukup, Jane R.; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02120 USA. [Baer, Heather J.; Karson, Andrew S.; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Baer, Heather J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Karson, Andrew S.] Massachusetts Gen Hosp, Dept Med, Clin Decis Support Unit, Boston, MA 02114 USA. [Bates, David W.] Partners HealthCare, Boston, MA USA. [Bates, David W.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Baer, HJ (reprint author), Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 1620 Tremont St, Boston, MA 02120 USA. EM hbaer@partners.org FU AHRQ HHS [K01HS019789] NR 8 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP 23 PY 2013 VL 173 IS 17 BP 1648 EP 1652 DI 10.1001/jamainternmed.2013.7815 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 228SU UT WOS:000325210600021 PM 23835808 ER PT J AU Caverly, TJ Prochazka, AV AF Caverly, Tanner J. Prochazka, Allan V. TI General Health Checks in Adults Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Caverly, Tanner J.] Univ Colorado, Sch Med, Div Gen Internal Med, Aurora, CO USA. [Prochazka, Allan V.] Denver VA Med Ctr, Denver, CO 80200 USA. RP Prochazka, AV (reprint author), Denver VA Med Ctr, 1055 Clermont, Denver, CO 80200 USA. EM Allan.Prochazka@va.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP 23 PY 2013 VL 173 IS 17 BP 1658 EP 1658 DI 10.1001/jamainternmed.2013.8194 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 228SU UT WOS:000325210600028 PM 24061395 ER PT J AU Islam, SA Ling, MF Leung, J Shreffler, WG Luster, AD AF Islam, Sabina A. Ling, Morris F. Leung, John Shreffler, Wayne G. Luster, Andrew D. TI Identification of human CCR8 as a CCL18 receptor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID C-C CHEMOKINE; T-CELLS; EOSINOPHILIC ESOPHAGITIS; ATOPIC-DERMATITIS; PULMONARY-FIBROSIS; DENDRITIC CELLS; INVOLVEMENT; ACTIVATION; EXPRESSION; AGONIST AB The CC chemokine ligand 18 (CCL18) is one of the most highly expressed chemokines in human chronic inflammatory diseases. An appreciation of the role of CCL18 in these diseases has been hampered by the lack of an identified chemokine receptor. We report that the human chemokine receptor CCR8 is a CCL18 receptor. CCL18 induced chemotaxis and calcium flux of human CCR8-transfected cells. CCL18 bound with high affinity to CCR8 and induced its internalization. Human CCL1, the known endogenous CCR8 ligand, and CCL18 competed for binding to CCR8-transfected cells. Further, CCL1 and CCL18 induced heterologous cross-desensitization of CCR8-transfected cells and human Th2 cells. CCL18 induced chemotaxis and calcium flux of human activated highly polarized Th2 cells through CCR8. Wild-type but not Ccr8-deficient activated mouse Th2 cells migrated in response to CCL18. CCL18 and CCR8 were coexpressed in esophageal biopsy tissue from individuals with active eosinophilic esophagitis (EoE) and were present at markedly higher levels compared with esophageal tissue isolated from EoE patients whose disease was in remission or in normal controls. Identifying CCR8 as a chemokine receptor for CCL18 will help clarify the biological role of this highly expressed chemokine in human disease. C1 [Islam, Sabina A.; Ling, Morris F.; Leung, John; Shreffler, Wayne G.; Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu OI Ling, Morris/0000-0002-9657-8960 FU National Institutes of Health grant [R37AI040618, U19AI095261] FX This work is funded by National Institutes of Health grant R37AI040618 and U19AI095261 to A.D. Luster. NR 30 TC 28 Z9 30 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 23 PY 2013 VL 210 IS 10 BP 1889 EP 1898 DI 10.1084/jem.20130240 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 223NR UT WOS:000324813000001 PM 23999500 ER PT J AU Kreslavsky, T Kim, HJ Koralov, SB Ghitza, D Buch, T Cantor, H Rajewsky, K von Boehmer, H AF Kreslavsky, Taras Kim, Hye-Jung Koralov, Sergei B. Ghitza, Dvora Buch, Thorsten Cantor, Harvey Rajewsky, Klaus von Boehmer, Harald TI Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL-RECEPTOR; V(D)J RECOMBINATION; RAG-2 ACCUMULATION; TRANSGENIC MICE; CLONAL DELETION; EXPRESSION; TOLERANCE; GENE; REARRANGEMENT; ACTIVATION AB Antigen receptor editing-a process of secondary rearrangements of antigen receptor genes in autoreactive lymphocytes-is a well-established tolerance mechanism in B cells, whereas its role in T cells remains controversial. Here, we investigated this issue using a novel Tcra knock-in locus, which ensured appropriate timing of TCR alpha expression and allowed secondary rearrangements. Under these conditions the only response to self-antigen that could be unambiguously identified was negative selection of CD4/CD8 double positive thymocytes. No evidence could be obtained for antigen-induced TCR editing, whereas replacement of the transgenic TCR alpha chain by ongoing gene rearrangement occurred in some cells irrespective of the presence or absence of self-antigen. C1 [Kreslavsky, Taras; Kim, Hye-Jung; Cantor, Harvey; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Koralov, Sergei B.; Ghitza, Dvora; Rajewsky, Klaus] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Koralov, Sergei B.; Ghitza, Dvora; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Buch, Thorsten] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81545 Munich, Germany. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu FU National Institutes of Health [R01 A145846, R01 A151378, R37 AI054636]; Swiss National Fund [SNF 310030_132713] FX These studies were supported by National Institutes of Health grants R01 A145846 and R01 A151378 to Harald von Boehmer and R37 AI054636 to Klaus Rajewsky, and Swiss National Fund SNF 310030_132713 grant to Thorsten Buch. NR 29 TC 7 Z9 7 U1 1 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 23 PY 2013 VL 210 IS 10 BP 1911 EP 1918 DI 10.1084/jem.20130876 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 223NR UT WOS:000324813000003 PM 23980099 ER PT J AU Crocker, B Lewandrowski, EL Lewandrowski, N Gregory, K Lewandrowski, K AF Crocker, Benjamin Lewandrowski, Elizabeth-Lee Lewandrowski, Nicole Gregory, Kimberly Lewandrowski, Kent TI Patient satisfaction with point-of-care laboratory testing: Report of a quality improvement program in an ambulatory practice of an academic medical center SO CLINICA CHIMICA ACTA LA English DT Article DE Point-of-care testing; Patient satisfaction; Primary care; Hemoglobin A1c; Lipid panel; Comprehensive metabolic panel ID FACILITATION; INVOLVEMENT AB Background: Point-of-care laboratory testing (POCT) offers reduced turnaround time and may facilitate medical decision-making and improve clinical operations. However, there is very little published data concerning the impact of POCT on patient satisfaction. Methods: We implemented POCT for hemoglobin A1c, lipid panel and comprehensive metabolic panel in a primary care practice and monitored patient satisfaction with on-site testing using an anonymous survey. Results: A total of 97 surveys (65% response rate) were reviewed. On a scale of 1 (poor) to 4 (excellent) the mean response to the question "Compared with your past experiences of physician office visits that did not have on-site testing please rank your overall level of satisfaction with today's office visit" was 3.96. In 34 surveys a free text comment was included which was uniformly very positive. Conclusions: Our study strongly indicates a high level of patient satisfaction with on-site POCT in a primary care setting. (c) 2013 Published by Elsevier B.V. C1 [Crocker, Benjamin] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lewandrowski, Elizabeth-Lee; Lewandrowski, Nicole; Gregory, Kimberly; Lewandrowski, Kent] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Crocker, Benjamin; Lewandrowski, Elizabeth-Lee; Lewandrowski, Kent] Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Gray 5 Chem, Boston, MA 02114 USA. EM klewandrowski@partners.org FU Siemens Point-of-Care; Abaxis FX This study was funded or supported in part by Siemens Point-of-Care and Abaxis. NR 8 TC 9 Z9 9 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD SEP 23 PY 2013 VL 424 BP 8 EP 11 DI 10.1016/j.cca.2013.04.025 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 226NH UT WOS:000325042600003 PM 23669184 ER PT J AU Torres-Garcia, D Cruz-Lagunas, A Figueroa, MCGS Fernandez-Plata, R Baez-Saldana, R Mendoza-Milla, C Barquera, R Carrera-Eusebio, A Ramirez-Bravo, S Campos, L Angeles, J Vargas-Alarcon, G Granados, J Gopal, R Khader, SA Yunis, EJ Zuniga, JQ AF Torres-Garcia, Diana Cruz-Lagunas, Alfredo Garcia-Sancho Figueroa, Ma Cecilia Fernandez-Plata, Rosario Baez-Saldana, Renata Mendoza-Milla, Criselda Barquera, Rodrigo Carrera-Eusebio, Aida Ramirez-Bravo, Salomon Campos, Lizeth Angeles, Javier Vargas-Alarcon, Gilberto Granados, Julio Gopal, Radha Khader, Shabaana A. Yunis, Edmond J. Zuniga, Joaquin TI Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Tuberculosis; rs352139; TLRs; Gene polymorphisms; Susceptibility; TLR9 ID PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; GLOBAL EPIDEMIOLOGY; NEW-WORLD; POLYMORPHISMS; ASSOCIATION; INFECTION; TLR9; METAANALYSIS; RESISTANCE AB Background: The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. Methods: We carried out a case-control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. Results: We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR=2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected. Conclusions: Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians. C1 [Torres-Garcia, Diana; Cruz-Lagunas, Alfredo; Campos, Lizeth; Zuniga, Joaquin] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Immunol, Mexico City 14080, DF, Mexico. [Garcia-Sancho Figueroa, Ma Cecilia; Fernandez-Plata, Rosario] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Epidemiol & Social Sci, Mexico City, DF, Mexico. [Baez-Saldana, Renata] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept TB, Mexico City, DF, Mexico. [Mendoza-Milla, Criselda] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Pulm Fibrosis, Mexico City, DF, Mexico. [Barquera, Rodrigo] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Mol Genet Lab, Mexico City, DF, Mexico. [Carrera-Eusebio, Aida; Ramirez-Bravo, Salomon] Jurisdicc Sanitaria No 3 Tuxtepec, Serv Salud Estado Oaxaca, Oaxaca, Mexico. [Angeles, Javier; Vargas-Alarcon, Gilberto] Inst Nacl Cardiol Ignacio Chevez, Mexico City, DF, Mexico. [Granados, Julio] Inst Nacl Ciencias Med Nutr Salvador Zubiran, Dept Transplants, Mexico City, DF, Mexico. [Gopal, Radha; Khader, Shabaana A.] UPMC, Childrens Hosp Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Yunis, Edmond J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Figueroa, MCGS (reprint author), Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Epidemiol & Social Sci, Mexico City, DF, Mexico. EM cegarsan@netscape.net; joazu@yahoo.com OI CRUZ-LAGUNAS, ALFREDO/0000-0001-5487-5919 FU National Council of Science and Technology of Mexico (Conacyt) [115497] FX This work was supported by the Grant number 115497 from the National Council of Science and Technology of Mexico (Conacyt). NR 45 TC 18 Z9 18 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD SEP 21 PY 2013 VL 11 AR 220 DI 10.1186/1479-5876-11-220 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 228XW UT WOS:000325226400001 PM 24053111 ER PT J AU Safai, S Trofimov, A Adams, JA Engelsman, M Bortfeld, T AF Safai, S. Trofimov, A. Adams, J. A. Engelsman, M. Bortfeld, T. TI The rationale for intensity-modulated proton therapy in geometrically challenging cases SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TREATMENT UNCERTAINTIES; OPTIMIZATION; BEAM; RADIOTHERAPY; VERIFICATION; RADIOGRAPHY; SENSITIVITY; ROBUSTNESS; DESIGN; GANTRY AB Intensity-modulated proton therapy (IMPT) delivered with beam scanning is currently available at a limited number of proton centers. However, a simplified form of IMPT, the technique of field 'patching', has long been a standard practice in proton therapy centers. In field patching, different parts of the target volume are treated from different directions, i.e., a part of the tumor gets either full dose from a radiation field, or almost no dose. Thus, patching represents a form of binary intensity modulation. This study explores the limitations of the standard binary field patching technique, and evaluates possible dosimetric advantages of continuous dose modulations in IMPT. Specifics of the beam delivery technology, i.e., pencil beam scanning versus passive scattering and modulation, are not investigated. We have identified two geometries of target volumes and organs at risk (OAR) in which the use of field patching is severely challenged. We focused our investigations on two patient cases that exhibit these geometries: a paraspinal tumor case and a skull-base case. For those cases we performed treatment planning comparisons of three-dimensional conformal proton therapy (3DCPT) with field patching versus IMPT, using commercial and in-house software, respectively. We also analyzed the robustness of the resulting plans with respect to systematic setup errors of +/- 1 mm and range errors of +/- 2.5 mm. IMPT is able to better spare OAR while providing superior dose coverage for the challenging cases identified above. Both 3DCPT and IMPT are sensitive to setup errors and range uncertainties, with IMPT showing the largest effect. Nevertheless, when delivery uncertainties are taken into account IMPT plans remain superior regarding target coverage and OAR sparing. On the other hand, some clinical goals, such as the maximum dose to OAR, are more likely to be unmet with IMPT under large range errors. IMPT can potentially improve target coverage and OAR sparing in challenging cases, even when compared with the relatively complicated and time consuming field patching technique. While IMPT plans tend to be more sensitive to delivery uncertainties, their dosimetric advantage generally holds. Robust treatment planning techniques may further reduce the sensitivity of IMPT plans. C1 [Safai, S.; Trofimov, A.; Adams, J. A.; Engelsman, M.; Bortfeld, T.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Safai, S (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. EM sairos.safai@psi.ch FU Swiss National Science Foundation; US National Cancer Institute [POI-CA021239] FX This study was supported by the Swiss National Science Foundation and the US National Cancer Institute award POI-CA021239 'Optimizing Proton Radiation Therapy'. NR 32 TC 6 Z9 6 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2013 VL 58 IS 18 BP 6337 EP 6353 DI 10.1088/0031-9155/58/18/6337 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 220HL UT WOS:000324573400008 PM 23965339 ER PT J AU Goldhirsch, A Gelber, RD Piccart-Gebhart, MJ de Azambuja, E Procter, M Suter, TM Jackisch, C Cameron, D Weber, HA Heinzmann, D Dal Lago, L McFadden, E Dowsett, M Untch, M Gianni, L Bell, R Kohne, CH Vindevoghel, A Andersson, M Brunt, AM Otero-Reyes, D Song, S Smith, I Leyland-Jones, B Baselga, J AF Goldhirsch, Aron Gelber, Richard D. Piccart-Gebhart, Martine J. de Azambuja, Evandro Procter, Marion Suter, Thomas M. Jackisch, Christian Cameron, David Weber, Harald A. Heinzmann, Dominik Dal Lago, Lissandra McFadden, Eleanor Dowsett, Mitch Untch, Michael Gianni, Luca Bell, Richard Koehne, Claus-Henning Vindevoghel, Anita Andersson, Michael Brunt, A. Murray Otero-Reyes, Douglas Song, Santai Smith, Ian Leyland-Jones, Brian Baselga, Jose CA Herceptin Adjuvant HERA Trial TI 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial SO LANCET LA English DT Article ID FOLLOW-UP; NSABP B-31; CHEMOTHERAPY; THERAPY AB Background Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatment, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial. Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant chemotherapy, adjuvant chemotherapy, or both in 5102 patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. The comparison of 2 years versus 1 year of trastuzumab treatment involved a landmark analysis of 3105 patients who were disease-free 12 months after randomisation to one of the trastuzumab groups, and was planned after observing at least 725 disease-free survival events. The updated intention-to-treat comparison of 1 year trastuzumab treatment versus observation alone in 3399 patients at a median follow-up of 8 years (range 0-10) is also reported. This study is registered with ClinicalTrials.gov, number NCT00045032. Findings We recorded 367 events of disease-free survival in 1552 patients in the 1 year group and 367 events in 1553 patients in the 2 year group (hazard ratio [HR] 0.99, 95% CI 0.85-1.14, p=0.86). Grade 3-4 adverse events and decreases in left ventricular ejection fraction during treatment were reported more frequently in the 2 year treatment group than in the 1 year group (342 [20.4%] vs 275 [16.3%] grade 3-4 adverse events, and 120 [7.2%] vs 69 [4.1%] decreases in left ventricular ejection fraction, respectively). HRs for a comparison of 1 year of trastuzumab treatment versus observation were 0.76 (95% CI 0.67-0.86, p<0.0001) for disease-free survival and 0.76 (0.65-0.88, p=0.0005) for overall survival, despite crossover of 884 (52%) patients from the observation group to trastuzumab therapy. Interpretation 2 years of adjuvant trastuzumab is not more effective than is 1 year of treatment for patients with HER2-positive early breast cancer. 1 year of treatment provides a significant disease-free and overall survival benefit compared with observation and remains the standard of care. C1 [Goldhirsch, Aron] European Inst Oncol, Dept Med, I-20141 Milan, Italy. [Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gelber, Richard D.; Procter, Marion; McFadden, Eleanor] Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium. [Suter, Thomas M.] Univ Hosp Bern, Inselspital, Swiss Cardiovasc Ctr, Bern, Switzerland. [Cameron, David] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Cameron, David] Univ Edinburgh, Dept Oncol, Edinburgh, Midlothian, Scotland. [Weber, Harald A.; Heinzmann, Dominik] F Hoffmann La Roche, Basel, Switzerland. [Dowsett, Mitch] Royal Marsden Natl Hlth Serv Trust, Acad Dept Biochem, London, England. [Untch, Michael] Helios Klinikum Berlin Buch, Dept Gynecol & Obstet & Multidisciplinary, Breast Canc Ctr, Berlin, Germany. [Gianni, Luca] Osped San Raffaele, Dept Med Oncol, Milan, Italy. [Bell, Richard] Geelong Hosp, Andrew Love Canc Ctr, Geelong, Vic, Australia. [Koehne, Claus-Henning] Klinikum Oldenburg, Klin Onkol Hamatol, Oldenburg, Germany. [Vindevoghel, Anita] Clin & Maternit St Elisabet, Namur, Belgium. [Andersson, Michael] Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. [Brunt, A. Murray] Univ Hosp North Staffordshire, Ctr Canc, Stoke On Trent, Staffs, England. [Brunt, A. Murray] Keele Univ, Stoke On Trent, Staffs, England. [Otero-Reyes, Douglas] Ctr Int Med Adv, Dept Oncol, San Jose, Costa Rica. [Song, Santai] 307 Hosp PLA, Ctr Canc, Beijing, Peoples R China. Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England. [Smith, Ian] Inst Canc Res, London SW3 6JB, England. [Leyland-Jones, Brian] Sanford Breast Canc Res, Sioux Falls, SD USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med, Via Ripamonti 435, I-20141 Milan, Italy. EM aaron.goldhirsch@ieo.it FU F Hoffmann-La Roche (Roche) FX F Hoffmann-La Roche (Roche). NR 16 TC 149 Z9 158 U1 4 U2 41 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD SEP 21 PY 2013 VL 382 IS 9897 BP 1021 EP 1028 DI 10.1016/S0140-6736(13)61094-6 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 222PB UT WOS:000324742200022 PM 23871490 ER PT J AU Jacobson, CA Freedman, AS AF Jacobson, Caron A. Freedman, Arnold S. TI One Size Does Not Fit All in Follicular Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID 1ST-LINE TREATMENT; PLUS RITUXIMAB; TRIAL; CYCLOPHOSPHAMIDE; MAINTENANCE; VINCRISTINE; COMBINATION; SURVIVAL; INDOLENT; PHASE-3 C1 [Jacobson, Caron A.; Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jacobson, CA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2013 VL 31 IS 27 BP 3307 EP 3308 DI 10.1200/JCO.2013.50.0454 PG 2 WC Oncology SC Oncology GA 301NH UT WOS:000330538500003 PM 23960176 ER PT J AU Kumar, P Temel, JS AF Kumar, Pallavi Temel, Jennifer S. TI End-of-Life Care Discussions in Patients With Advanced Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CODE STATUS DOCUMENTATION; HOSPITAL CARDIAC-ARREST; SHARED DECISION-MAKING; LUNG-CANCER; CARDIOPULMONARY-RESUSCITATION; PALLIATIVE CARE; BREAST-CANCER; MENTAL-HEALTH; IMPROVE CARE AB A 70-year-old man with a history of a Gleason 9 (4 + 5) adenocarcinoma 10 years before that was treated with a radical prostatectomy presented to his primary care physician with a complaint of rectal pain that had persisted for several weeks. A large palpable mass was found on a digital rectal exam and was noted on sigmoidoscopy to cause extrinsic compression of the rectum. A biopsy of the perirectal mass was consistent with metastatic carcinoma that was consistent with a recurrent metastasis of his previous prostate adenocarcinoma, now with small-cell transformation. A computed tomography scan showed the perirectal mass arising from the prior prostatectomy bed, as well as a large hepatic mass and bilateral lung nodules that were consistent with metastatic disease (Fig 1). He had lost 20 lbs over 3 to 4 weeks and complained of progressive fatigue, poor appetite, severe tenesmus, and rectal pain. He presented to the medical oncology department for an initial consultation. Given his significant rectal pain and declining functional status, he was referred for palliative pelvic radiation to be given with concurrent single-agent chemotherapy. The patient had been living independently on the West Coast but had relocated to the East Coast to be closer to his adult children. He stressed that his wishes were to remain as independent and functional as possible. He named his eldest son as his health care proxy but did not have an advance directive or living will. After the visit, the patient's daughter approached the oncologist with concerns about discussing "CPR" (cardiopulmonary resuscitation) and "life support," and indicated that this discussion would be overwhelming for her father. C1 [Kumar, Pallavi; Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Kumar, P (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 49 TC 12 Z9 12 U1 4 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2013 VL 31 IS 27 BP 3315 EP 3319 DI 10.1200/JCO.2013.49.6562 PG 5 WC Oncology SC Oncology GA 301NH UT WOS:000330538500006 PM 23897952 ER PT J AU Sequist, LV Yang, JCH Yamamoto, N O'Byrne, K Hirsh, V Mok, T Geater, SL Orlov, S Tsai, CM Boyer, M Su, WC Bennouna, J Kato, T Gorbunova, V Lee, KH Shah, R Massey, D Zazulina, V Shahidi, M Schuler, M AF Sequist, Lecia V. Yang, James Chih-Hsin Yamamoto, Nobuyuki O'Byrne, Kenneth Hirsh, Vera Mok, Tony Geater, Sarayut Lucien Orlov, Sergey Tsai, Chun-Ming Boyer, Michael Su, Wu-Chou Bennouna, Jaafar Kato, Terufumi Gorbunova, Vera Lee, Ki Hyeong Shah, Riyaz Massey, Dan Zazulina, Victoria Shahidi, Mehdi Schuler, Martin TI Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FACTOR RECEPTOR MUTATIONS; 1ST-LINE TREATMENT; SUPPORTIVE CARE; CLINICAL-TRIALS; OPEN-LABEL; CANCER; CHEMOTHERAPY; GEFITINIB; ERLOTINIB; MULTICENTER AB Purpose The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). Patients and Methods In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). Results A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatment-related adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. Conclusion Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations. (C) 2013 by American Society of Clinical Oncology C1 [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Tsai, Chun-Ming] Taipei Vet Gen Hosp, Taipei, Taiwan. [Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. [Yamamoto, Nobuyuki] Shizuoka Canc Ctr, Shizuoka, Japan. [Kato, Terufumi] Kanagawa Cardiovasc & Resp Ctr, Yokohama, Kanagawa, Japan. [O'Byrne, Kenneth] St James Hosp, Dublin 8, Ireland. [Hirsh, Vera] McGill Univ, Montreal, PQ, Canada. [Mok, Tony] Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Geater, Sarayut Lucien] Songklanagarind Hosp, Songkhla, Thailand. [Orlov, Sergey] Pavlov State Med Univ, St Petersburg, Russia. [Gorbunova, Vera] GU Russian Oncol Res Ctr, Moscow, Russia. [Boyer, Michael] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. [Bennouna, Jaafar] Inst Cancerol Ouest Site Rene Gauducheau, Nantes, France. [Lee, Ki Hyeong] Chungbuk Natl Univ Hosp, Cheongju, South Korea. [Shah, Riyaz] Maidstone Hlth Author, Maidstone & Tunbridge Wells Natl Hlth Serv Trust, Maidstone, Kent, England. [Massey, Dan; Zazulina, Victoria; Shahidi, Mehdi] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England. [Schuler, Martin] Univ Duisburg Essen, West German Canc Ctr, Essen, Germany. RP Yang, JCH (reprint author), Natl Taiwan Univ, Taipei 10764, Taiwan. EM chihyang@ntu.edu.tw RI bennouna, jaafar/K-9350-2015; Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Yang, James Chih-Hsin/0000-0002-5586-5138 FU Boehringer Ingelheim; AstraZeneca FX Research Funding: Lecia V. Sequist, Boehringer Ingelheim; Tony Mok, AstraZeneca; Michael Boyer, Boehringer Ingelheim; Terufumi Kato, Boehringer Ingelheim; Martin Schuler, Boehringer Ingelheim NR 36 TC 703 Z9 741 U1 10 U2 75 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2013 VL 31 IS 27 BP 3327 EP + DI 10.1200/JCO.2012.44.2806 PG 11 WC Oncology SC Oncology GA 301NH UT WOS:000330538500008 PM 23816960 ER PT J AU Yang, JCH Hirsh, V Schuler, M Yamamoto, N O'Byrne, KJ Mok, TSK Zazulina, V Shahidi, M Lungershausen, J Massey, D Palmer, M Sequist, LV AF Yang, James Chih-Hsin Hirsh, Vera Schuler, Martin Yamamoto, Nobuyuki O'Byrne, Kenneth J. Mok, Tony S. K. Zazulina, Victoria Shahidi, Mehdi Lungershausen, Juliane Massey, Dan Palmer, Michael Sequist, Lecia V. TI Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With EGFR Mutations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER CLINICAL-TRIALS; 1ST-LINE TREATMENT; OPEN-LABEL; CHEMOTHERAPY; ERLOTINIB; GEFITINIB; MULTICENTER; ONCOLOGY; QLQ-C30 AB Purpose Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed. Patients and Methods Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2: 1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time. Results Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P = .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P < .001) and dyspnea (P < .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P < .001), role (P = .004), and cognitive (P = .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P < .01). Conclusion In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy. (C) 2013 by American Society of Clinical Oncology C1 [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Hirsh, Vera] McGill Univ, Montreal, PQ, Canada. [Schuler, Martin] Univ Duisburg Essen, West German Canc Ctr, Essen, Germany. [Lungershausen, Juliane] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Yamamoto, Nobuyuki] Shizuoka Canc Ctr, Shizuoka, Japan. [O'Byrne, Kenneth J.] St James Hosp, Dublin 8, Ireland. [Mok, Tony S. K.] Chinese Univ Hong Kong, State Key Lab Southern China, Hong Kong Canc Inst, Hong Kong, Hong Kong, Peoples R China. [Zazulina, Victoria; Shahidi, Mehdi; Massey, Dan] Boehringer Ingelheim Ltd, Bracknell, Berks, England. [Palmer, Michael] Keele Univ, Keele ST5 5BG, Staffs, England. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. RP Yang, JCH (reprint author), Natl Taiwan Univ, Grad Inst Oncol, 7 Chung Shan South Rd, Taipei 10764, Taiwan. EM chihyang@ntu.edu.tw OI Yang, James Chih-Hsin/0000-0002-5586-5138 FU Boehringer Ingelheim FX We gratefully acknowledge the patients, their families, and their caregivers for participation in this study. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Suzanne Patel of Ogilvy Healthworld Medical Education during the preparation of this article. NR 28 TC 108 Z9 123 U1 0 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2013 VL 31 IS 27 BP 3342 EP + DI 10.1200/JCO.2012.46.1764 PG 13 WC Oncology SC Oncology GA 301NH UT WOS:000330538500010 PM 23816967 ER PT J AU Qian, ZR Ter-Minassian, M Chan, JA Imamura, Y Hooshmand, SM Kuchiba, A Morikawa, T Brais, LK Daskalova, A Heafield, R Lin, XH Christiani, DC Fuchs, CS Ogino, S Kulke, MH AF Qian, Zhi Rong Ter-Minassian, Monica Chan, Jennifer A. Imamura, Yu Hooshmand, Susanne M. Kuchiba, Aya Morikawa, Teppei Brais, Lauren K. Daskalova, Anastassia Heafield, Rachel Lin, Xihong Christiani, David C. Fuchs, Charles S. Ogino, Shuji Kulke, Matthew H. TI Prognostic Significance of MTOR Pathway Component Expression in Neuroendocrine Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PANCREATIC ENDOCRINE TUMORS; RENAL-CELL CARCINOMA; AKT/MAMMALIAN TARGET; RAPAMYCIN PATHWAY; ACTIVATION; CANCER; AKT; DOWNSTREAM; EVEROLIMUS; PROTEINS AB Purpose Clinical studies have implicated the mechanistic target of rapamycin (serine/threonine kinase; MTOR) pathway in the regulation of neuroendocrine tumor (NET) growth. We explored whether expression of MTOR pathway components has prognostic significance in NET patients. Patients and Methods We evaluated immunohistochemical expression of MTOR and phospho (p) -MTOR; its downstream targets RPS6KB1, RPS6, and EIF4EBP1; and its upstream regulators, in a cohort of 195 archival neuroendocrine tumors. We correlated expression levels with clinical outcomes, after adjusting for other prognostic variables. Results We observed anticipated correlations between expression of upstream components of the MTOR pathway and their downstream targets. Expression of PIK3CA, MTOR, or p-EIF4EBP1 was associated with high MKI67 (Ki-67) labeling index. We failed to identify clinical correlations associated with expression of the upstream regulators TSC1, TSC2, AKT, p-AKT, PDPK1, PTEN, PIK3R1, or PIK3CA. In contrast, high expression of MTOR or its activated downstream targets p-RPS6KB1, p-RPS6, or p-EIF4EBP1 was associated with adverse clinical outcomes. Conclusion Our observations suggest that expression of MTOR or its downstream targets may be adverse prognostic factors in neuroendocrine tumors. (C) 2013 by American Society of Clinical Oncology C1 [Qian, Zhi Rong; Ter-Minassian, Monica; Chan, Jennifer A.; Imamura, Yu; Hooshmand, Susanne M.; Kuchiba, Aya; Morikawa, Teppei; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Fuchs, Charles S.; Ogino, Shuji; Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Qian, Zhi Rong; Ter-Minassian, Monica; Chan, Jennifer A.; Imamura, Yu; Hooshmand, Susanne M.; Kuchiba, Aya; Morikawa, Teppei; Brais, Lauren K.; Daskalova, Anastassia; Heafield, Rachel; Fuchs, Charles S.; Ogino, Shuji; Kulke, Matthew H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ter-Minassian, Monica; Lin, Xihong; Christiani, David C.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Fuchs, Charles S.; Ogino, Shuji] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Qian, ZR (reprint author), Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave,Room M-420, Boston, MA 02115 USA. EM Zhirong_Qian@dfci.harvard.edu FU Novartis Pharmaceuticals; Raymond and Beverly Sackler American Association of Cancer Research Fellowship for Ileal Carcinoid Research; National Institutes of Health [R01 CA151532-01A1, 5P50CA127003-05] FX Supported by a grant from Novartis Pharmaceuticals, by the Raymond and Beverly Sackler American Association of Cancer Research Fellowship for Ileal Carcinoid Research (M. T.-M.), and in part by Grants No. R01 CA151532-01A1 and 5P50CA127003-05 (Gastrointestinal Cancer SPORE; M. H. K.) from the National Institutes of Health. NR 39 TC 23 Z9 25 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2013 VL 31 IS 27 BP 3418 EP + DI 10.1200/JCO.2012.46.6946 PG 9 WC Oncology SC Oncology GA 301NH UT WOS:000330538500019 PM 23980085 ER PT J AU Goss, PE Liedke, PER Chapman, JAW Shepherd, LE AF Goss, Paul E. Liedke, Pedro E. R. Chapman, Judy-Anne W. Shepherd, Lois E. TI Aromatase Inhibitors and Safety: Clinical or Statistical Significance? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liedke, Pedro E. R.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Chapman, Judy-Anne W.; Shepherd, Lois E.] NCIC Clin Trials Grp, Kingston, ON, Canada. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2013 VL 31 IS 27 BP 3439 EP 3440 DI 10.1200/JCO.2013.51.4893 PG 3 WC Oncology SC Oncology GA 301NH UT WOS:000330538500023 PM 23943834 ER PT J AU Ferreri, AJM Zucca, E Armitage, J Cavalli, F Batchelor, TT AF Ferreri, Andres J. M. Zucca, Emanuele Armitage, James Cavalli, Franco Batchelor, Tracy T. TI Ten Years of International Primary CNS Lymphoma Collaborative Group Studies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID NERVOUS-SYSTEM LYMPHOMA; DESCRIPTIVE ANALYSIS; HODGKIN-LYMPHOMA; INVOLVEMENT C1 [Ferreri, Andres J. M.] Ist Sci San Raffaele, I-20132 Milan, Italy. [Zucca, Emanuele; Cavalli, Franco] Oncol Inst Southern Switzerland, Bellinzona, Switzerland. [Armitage, James] Univ Nebraska Med Ctr, Eppley Canc Ctr, Omaha, NE USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Ferreri, AJM (reprint author), Ist Sci San Raffaele, I-20132 Milan, Italy. FU NCI NIH HHS [R13 CA124293] NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2013 VL 31 IS 27 BP 3444 EP 3445 DI 10.1200/JCO.2013.51.7557 PG 3 WC Oncology SC Oncology GA 301NH UT WOS:000330538500028 PM 23960177 ER PT J AU Kayani, WT Bandeali, SJ Lee, VV Elayda, M Khan, A Nambi, V Jneid, H Alam, M Wilson, JM Huang, HD Birnbaum, Y Ballantyne, CM Virani, SS AF Kayani, Waleed T. Bandeali, Salman J. Lee, Vei-Vei Elayda, MacArthur Khan, Anam Nambi, Vijay Jneid, Hani Alam, Mahboob Wilson, James M. Huang, Henry D. Birnbaum, Yochai Ballantyne, Christie M. Virani, Salim S. TI Association between statins and infections after coronary artery bypass grafting SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Statins; Infection; Coronary artery bypass grafting ID COMMUNITY-ACQUIRED PNEUMONIA; SURGICAL SITE INFECTIONS; PREOPERATIVE STATIN; CARDIAC-SURGERY; MORTALITY; RISK; THERAPY; INHIBITORS; OUTCOMES; DISEASE AB Background: We determined whether pre-operative statin therapy is associated with a decrease in the incidence of infections after coronary artery bypass grafting (CABG). Methods: A retrospective cohort study of 6253 patients undergoing isolated CABG, from the Texas Heart Institute Database from January 1, 2000 to December 31, 2010 (3869 receiving statins and 2384 not receiving statins) was conducted. Primary outcome was the development of any postoperative infection (composite of deep-sternal wound infection, leg harvest-site infection, pneumonia, or sepsis) after CABG. Secondary outcome was the association between pre-operative statin use and individual incidence of each aforementioned infection. Logistic regression analyses were performed. Results: Incidence of any postoperative infection in patients who received statins pre-operatively was 6.5% compared to 8.3% in patients who did not receive statins. Pre-operative statin therapy was associated with a significant reduction in the primary outcome (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.60-0.90) in adjusted models. Among individual secondary outcomes, pre-operative statin therapy was associated with a reduced incidence of sternal wound infections (2.5% vs. 3.2%, OR 0.6, 95% CI 0.5-0.8) and leg harvest site infections (0.6% vs. 1.3%, OR 0.46, 95% CI 0.2-0.8). Pre-operative statin therapy was not associated with a reduced incidence of pneumonia or sepsis. Conclusion: Pre-operative statin use is associated with a decrease in overall incidence of post-operative infections after CABG. We propose immunomodulatory effects of statins leading to a dampening of inflammatory cascade as the cause of our findings. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Kayani, Waleed T.; Bandeali, Salman J.; Nambi, Vijay; Jneid, Hani; Birnbaum, Yochai; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Virani, Salim S.] Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy & Qual Program, Houston, TX USA. [Lee, Vei-Vei; Elayda, MacArthur] St Lukes Episcopal Hosp, Texas Heart Inst, Dept Epidemiol & Biostat, Houston, TX USA. [Nambi, Vijay; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Nambi, Vijay; Ballantyne, Christie M.; Virani, Salim S.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Virani, Salim S.] Michael E DeBakey VA Med Ctr, Cardiol Sect, Houston, TX USA. [Alam, Mahboob] Memphis Vet Affairs Med Ctr, Cardiol Sect, Memphis, TN USA. [Wilson, James M.] St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiol, Houston, TX USA. [Nambi, Vijay; Jneid, Hani; Huang, Henry D.; Birnbaum, Yochai; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Khan, Anam] Aga Khan Univ, Karachi, Pakistan. RP Kayani, WT (reprint author), Baylor Coll Med, Dept Med, 1 Baylor Plaza, Houston, TX 77030 USA. EM kayani@bcm.edu OI Virani, Salim/0000-0001-9541-6954 FU Department of Veterans Affairs Health Services Research and Development Service (HSR&D) Career Development Award [CDA-09-028]; Abbott; AstraZeneca; Bristol-Myers Squibb; GlaxoSmithKline; Genentech; Kowa; Merck; Novartis; Roche; Sanofi-Synthelabo; Takeda; NIH; ADA; AHA; Anthera Pharmaceuticals Research collaboration GE; Medipattern; Tomtec FX Vijay Nambi: disclosures-National monitor, study sponsored by Anthera Pharmaceuticals Research collaboration GE, Medipattern, Tomtec.; Christie M Ballantyne: grant/research support (all paid to institution, not individual): Abbott, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Genentech, Kowa, Merck, Novartis, Roche, Sanofi-Synthelabo, Takeda, NIH, ADA, AHA.; Salim S. Virani: Dr. Virani is supported by a Department of Veterans Affairs Health Services Research and Development Service (HSR&D) Career Development Award (grant number: CDA-09-028). NR 37 TC 10 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 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 20 PY 2013 VL 168 IS 1 BP 117 EP 120 DI 10.1016/j.ijcard.2012.09.060 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231IL UT WOS:000325409800032 PM 23046597 ER PT J AU Vaduganathan, M Allegretti, AS Manchette, AM Patel, SS Olson, KR Bazari, H AF Vaduganathan, Muthiah Allegretti, Andrew S. Manchette, Anastasia M. Patel, Shalin S. Olson, Kristian R. Bazari, Hasan TI Intravenous moderate-dose bumetanide continuous infusion and severe musculoskeletal pain SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Adverse effects; Diuretics; Drug therapy; Heart failure ID DECOMPENSATED HEART-FAILURE; LOOP DIURETICS; OUTCOMES C1 [Vaduganathan, Muthiah; Allegretti, Andrew S.; Patel, Shalin S.; Olson, Kristian R.; Bazari, Hasan] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Manchette, Anastasia M.] Harvard Univ, Sch Med, Dept Pharm, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vaduganathan, M (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM mvaduganathan@partners.org NR 10 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 20 PY 2013 VL 168 IS 1 BP E29 EP E31 DI 10.1016/j.ijcard.2013.05.081 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231IL UT WOS:000325409800013 PM 23727101 ER PT J AU Wiechers, IR Perin, NC Cook-Deegan, R AF Wiechers, Ilse R. Perin, Noah C. Cook-Deegan, Robert TI The emergence of commercial genomics: analysis of the rise of a biotechnology subsector during the Human Genome Project, 1990 to 2004 SO GENOME MEDICINE LA English DT Article AB Background: Development of the commercial genomics sector within the biotechnology industry relied heavily on the scientific commons, public funding, and technology transfer between academic and industrial research. This study tracks financial and intellectual property data on genomics firms from 1990 through 2004, thus following these firms as they emerged in the era of the Human Genome Project and through the 2000 to 2001 market bubble. Methods: A database was created based on an early survey of genomics firms, which was expanded using three web-based biotechnology services, scientific journals, and biotechnology trade and technical publications. Financial data for publicly traded firms was collected through the use of four databases specializing in firm financials. Patent searches were conducted using firm names in the US Patent and Trademark Office website search engine and the DNA Patent Database. Results: A biotechnology subsector of genomics firms emerged in parallel to the publicly funded Human Genome Project. Trends among top firms show that hiring, capital improvement, and research and development expenditures continued to grow after a 2000 to 2001 bubble. The majority of firms are small businesses with great diversity in type of research and development, products, and services provided. Over half the public firms holding patents have the majority of their intellectual property portfolio in DNA-based patents. Conclusions: These data allow estimates of investment, research and development expenditures, and jobs that paralleled the rise of genomics as a sector within biotechnology between 1990 and 2004. C1 [Wiechers, Ilse R.; Perin, Noah C.; Cook-Deegan, Robert] Duke Univ, Inst Genome Sci & Policy, Ctr Publ Genom, Durham, NC 27708 USA. [Cook-Deegan, Robert] Duke Univ, Sanford Sch Publ Policy, Durham, NC 27708 USA. [Wiechers, Ilse R.] Yale Univ, Sch Med, Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. [Wiechers, Ilse R.] US Dept Vet Affairs, New Haven, CT 06520 USA. RP Wiechers, IR (reprint author), Duke Univ, Inst Genome Sci & Policy, Ctr Publ Genom, Box 90141, Durham, NC 27708 USA. EM ilse.wiechers@yale.edu OI Cook-Deegan, Robert/0000-0002-8251-4237 FU Ewing Marion Kauffman Foundation; US Department of Energy [P50 HG003391]; Duke Endowment; National Human Genome Research Institute FX This work was supported in part by grants from the Ewing Marion Kauffman Foundation, the National Human Genome Research Institute and US Department of Energy (P50 HG003391) and the Duke Endowment. The views do not necessarily represent those of the funders. The authors would like to thank the following students and research assistants at the Center for Genome Ethics, Law & Policy whose countless hours of data gathering and entry were invaluable: Phebe Ko, Suparna Salil, Whitney Laemmli, Joe Fore, Alessandra Colaianni, Daidree Tofano, Molly Nicholson, Stacy Lavin, Britt Russert, Marjorie Gurganus, Anupama Kotha, and Cindy Wang. NR 19 TC 1 Z9 1 U1 1 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD SEP 20 PY 2013 VL 5 AR 83 DI 10.1186/gm487 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 230GD UT WOS:000325324000001 PM 24050173 ER PT J AU Kim, T Vidal, GS Djurisic, M William, CM Birnbaum, ME Garcia, KC Hyman, BT Shatz, CJ AF Kim, Taeho Vidal, George S. Djurisic, Maja William, Christopher M. Birnbaum, Michael E. Garcia, K. Christopher Hyman, Bradley T. Shatz, Carla J. TI Human LilrB2 Is a beta-Amyloid Receptor and Its Murine Homolog PirB Regulates Synaptic Plasticity in an Alzheimer's Model SO SCIENCE LA English DT Article ID OCULAR-DOMINANCE PLASTICITY; VISUAL-CORTEX; PRION PROTEIN; MOUSE MODEL; SPINE LOSS; DISEASE; MYELIN; DEPRESSION; OLIGOMERS; COFILIN AB Soluble beta-amyloid (A beta) oligomers impair synaptic plasticity and cause synaptic loss associated with Alzheimer's disease (AD). We report that murine PirB (paired immunoglobulin-like receptor B) and its human ortholog LilrB2 (leukocyte immunoglobulin-like receptor B2), present in human brain, are receptors for A beta oligomers, with nanomolar affinity. The first two extracellular immunoglobulin (Ig) domains of PirB and LilrB2 mediate this interaction, leading to enhanced cofilin signaling, also seen in human AD brains. In mice, the deleterious effect of A beta oligomers on hippocampal long-term potentiation required PirB, and in a transgenic model of AD, PirB not only contributed to memory deficits present in adult mice, but also mediated loss of synaptic plasticity in juvenile visual cortex. These findings imply that LilrB2 contributes to human AD neuropathology and suggest therapeutic uses of blocking LilrB2 function. C1 [Kim, Taeho; Vidal, George S.; Djurisic, Maja; Shatz, Carla J.] Stanford Univ, James H Clark Ctr, Dept Biol & Neurobiol, Stanford, CA 94305 USA. [Kim, Taeho; Vidal, George S.; Djurisic, Maja; Shatz, Carla J.] Stanford Univ, James H Clark Ctr, Dept BioX, Stanford, CA 94305 USA. [William, Christopher M.; Hyman, Bradley T.] Massachusetts Gen Hosp, Neuropathol Serv, Charlestown, MA 02129 USA. [Birnbaum, Michael E.; Garcia, K. Christopher] Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Birnbaum, Michael E.; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. RP Kim, T (reprint author), Stanford Univ, James H Clark Ctr, Dept Biol & Neurobiol, Stanford, CA 94305 USA. EM tkim808@stanford.edu; cshatz@stanford.edu OI William, Christopher/0000-0001-8933-1639 FU NIH [NS069375, EY02858, 5T32EY020485, K08NS069811, 5R01AG041507]; G. Harold and Leila Y. Mathers Charitable Foundation; Ellison Medical Foundation; Regina Casper Stanford Graduate Fellowship; Alzheimer Disease Research Center (NIH) [5P50AG005134]; NSF; HHMI FX We thank the Human Brain and Spinal Fluid Resource Center for providing human brain specimens; P. Kemper, C. Chechelski, and N. Sotelo-Kury for assistance with mouse husbandry; M. Stern for technical assistance; and C. Cepko (Harvard) for providing the pCAGIG vector. We also thank M. Frosch (MGH/Harvard) and M. Shamloo (Stanford Behavioral and Functional Neuroscience Laboratory, NIH grant NS069375) for helpful suggestions and advice. Supported by NIH grant EY02858 (C.J.S.), the G. Harold and Leila Y. Mathers Charitable Foundation (C.J.S.), the Ellison Medical Foundation (C.J.S.), NIH grant 5T32EY020485 (T.K.), a Regina Casper Stanford Graduate Fellowship (G.S.V.), NIH grant K08NS069811 (C.M.W.), NIH grant 5R01AG041507 (B.T.H.), an Alzheimer Disease Research Center pilot grant (NIH grant 5P50AG005134 to C.M.W.), NSF predoctoral fellowship (M.E.B.), and HHMI (K.C.G.). B.T.H. is on the Scientific Advisory Board of Neurophage and is a consultant and collaborator with Takeda Pharmaceutical Company, Bristol Meyer Squibb, Acumen, AZTherapeutics, Siemens, Sanofi, Neotope, and Fidelity Biosciences, none of which were involved in this study. C.J.S. and T.K. are inventors on a patent application assigned to the Board of Trustees of the Leland Stanford Junior University on methods and compositions for inhibiting the effects of beta-amyloid oligomers (U.S. provisional application no. 61/777,835). NR 40 TC 106 Z9 111 U1 6 U2 70 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 20 PY 2013 VL 341 IS 6152 BP 1399 EP 1404 DI 10.1126/science.1242077 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 220PK UT WOS:000324597200048 PM 24052308 ER PT J AU Zhang, R Turka, LA AF Zhang, Ruan Turka, Laurence A. TI A Breath of Fresh Aire SO IMMUNITY LA English DT Editorial Material ID T-CELL ANERGY; TOLERANCE C1 [Zhang, Ruan] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Zhang, R (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St,Room 5101, Boston, MA 02129 USA. EM rzhang5@partners.org NR 9 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD SEP 19 PY 2013 VL 39 IS 3 BP 427 EP 429 DI 10.1016/j.immuni.2013.08.022 PG 4 WC Immunology SC Immunology GA AA2UM UT WOS:000330949600006 PM 24054325 ER PT J AU Henrickson, SE Perro, M Loughhead, SM Senman, B Stutte, S Quigley, M Alexe, G Iannacone, M Flynn, MP Omid, S Jesneck, JL Imam, S Mempel, TR Mazo, IB Haining, WN von Andrian, UH AF Henrickson, Sarah E. Perro, Mario Loughhead, Scott M. Senman, Balimkiz Stutte, Susanne Quigley, Michael Alexe, Gabriela Iannacone, Matteo Flynn, Michael P. Omid, Shaida Jesneck, Jonathan L. Imam, Sabrina Mempel, Thorsten R. Mazo, Irina B. Haining, W. Nicholas von Andrian, Ulrich H. TI Antigen Availability Determines CD8(+) T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions SO IMMUNITY LA English DT Article ID LYMPH-NODES; IN-VIVO; TRANSCRIPTION FACTOR; STOP SIGNAL; EFFECTOR; DIFFERENTIATION; TOLERANCE; DYNAMICS; ACTIVATION; INDUCTION AB T cells are activated by antigen (Ag)-bearing dendritic cells (DCs) in lymph nodes in three phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8(+) T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, whereas higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation but yielded different transcriptome signatures at 12 hr and 24 hr. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics. C1 [Henrickson, Sarah E.; Perro, Mario; Loughhead, Scott M.; Senman, Balimkiz; Stutte, Susanne; Iannacone, Matteo; Flynn, Michael P.; Omid, Shaida; Mazo, Irina B.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Quigley, Michael; Alexe, Gabriela; Jesneck, Jonathan L.; Imam, Sabrina; Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Quigley, Michael; Alexe, Gabriela; Jesneck, Jonathan L.; Imam, Sabrina; Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. EM uva@hms.harvard.edu FU NIH [AI069259, AI072252]; MSTP at Harvard Medical School; Osaka University Immunology Frontier Research Center (iFREC) FX We thank T. Buschman for assistance with programming and G. Cheng and M. Perdue for technical and secretarial assistance, respectively. This work was supported by NIH grants AI069259 and AI072252 to U. H. v. A. and MSTP funding at Harvard Medical School and a Osaka University Immunology Frontier Research Center (iFREC) Postdoctoral Fellowship to S.E.H. NR 58 TC 34 Z9 34 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD SEP 19 PY 2013 VL 39 IS 3 BP 496 EP 507 DI 10.1016/j.immuni.2013.08.034 PG 12 WC Immunology SC Immunology GA AA2UM UT WOS:000330949600013 PM 24054328 ER PT J AU Mao, YD Castillo-Menendez, L Wang, LP Gu, C Herschhorn, A Desormeaux, A Finzi, A Xiang, SH Sodroski, JG AF Mao, Youdong Castillo-Menendez, Luis Wang, Liping Gu, Christopher Herschhorn, Alon Desormeaux, Anik Finzi, Andres Xiang, Shi-Hua Sodroski, Joseph G. TI Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Mao, Youdong; Castillo-Menendez, Luis; Wang, Liping; Gu, Christopher; Herschhorn, Alon; Sodroski, Joseph G.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Mao, Youdong; Castillo-Menendez, Luis; Wang, Liping; Gu, Christopher; Herschhorn, Alon; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Desormeaux, Anik; Finzi, Andres] Univ Montreal, Dept Microbiol & Immunol, Ctr Rech, Ctr Hosp Univ Montreal, Montreal, PQ H3A 2B4, Canada. [Xiang, Shi-Hua] Univ Nebraska, Nebraska Ctr Virol, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA. [Sodroski, Joseph G.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD SEP 19 PY 2013 VL 10 SU 1 BP S1 EP S1 AR O1 PG 1 WC Virology SC Virology GA 240LY UT WOS:000326099100002 ER PT J AU Bateman, BT Bykov, K Choudhry, NK Schneeweiss, S Gagne, JJ Polinski, JM Franklin, JM Doherty, M Fischer, MA Rassen, JA AF Bateman, Brian T. Bykov, Katsiaryna Choudhry, Niteesh K. Schneeweiss, Sebastian Gagne, Joshua J. Polinski, Jennifer M. Franklin, Jessica M. Doherty, Michael Fischer, Michael A. Rassen, Jeremy A. TI Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; PROTON-PUMP INHIBITORS; VENTILATOR-ASSOCIATED PNEUMONIA; INSTRUMENTAL VARIABLE ANALYSIS; MAJOR NONCARDIAC SURGERY; CRITICALLY III PATIENTS; ACID-SUPPRESSIVE DRUGS; 2 RECEPTOR ANTAGONISTS; ADMINISTRATIVE DATA; HEART-SURGERY AB Objective To examine the relation between the type of stress ulcer prophylaxis administered and the risk of postoperative pneumonia in patients undergoing coronary artery bypass grafting. Design Retrospective cohort study. Setting Premier Research Database. Participants: 21 214 patients undergoing coronary artery bypass graft surgery between 2004 and 2010; 9830 (46.3%) started proton pump inhibitors and 11 384 (53.7%) started H-2 receptor antagonists in the immediate postoperative period. Main outcome measure Occurrence of postoperative pneumonia, assessed using appropriate diagnostic codes. Results Overall, 492 (5.0%) of the 9830 patients receiving a proton pump inhibitor and 487 (4.3%) of the 11 384 patients receiving an H2 receptor antagonist developed postoperative pneumonia during the index hospital admission. After propensity score adjustment, an elevated risk of pneumonia associated with treatment with proton pump inhibitors compared with H2 receptor antagonists remained (relative risk 1.19, 95% confidence interval 1.03 to 1.38). In the instrumental variable analysis, use of a proton pump inhibitor (compared with an H-2 receptor antagonist) was associated with an increased risk of pneumonia of 8.2 (95% confidence interval 0.5 to 15.9) cases per 1000 patients. Conclusions Patients treated with proton pump inhibitors for stress ulcer had a small increase in the risk of postoperative pneumonia compared with patients treated with H-2 receptor antagonists; this risk remained after confounding was accounted for using multiple analytic approaches. C1 [Bateman, Brian T.; Bykov, Katsiaryna; Choudhry, Niteesh K.; Schneeweiss, Sebastian; Gagne, Joshua J.; Polinski, Jennifer M.; Franklin, Jessica M.; Doherty, Michael; Fischer, Michael A.; Rassen, Jeremy A.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Bykov, Katsiaryna; Choudhry, Niteesh K.; Schneeweiss, Sebastian; Gagne, Joshua J.; Polinski, Jennifer M.; Franklin, Jessica M.; Doherty, Michael; Fischer, Michael A.; Rassen, Jeremy A.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02120 USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. EM bbateman@partners.org RI Schneeweiss, Sebastian/C-2125-2013; OI Franklin, Jessica/0000-0002-8941-4116 FU Agency for Healthcare Research and Quality [K01 HS018088]; Agency for Healthcare Research and Quality; Harvard-Brigham Drug Safety and Risk Management Research Center; Food and Drug Administration; WHISCON LLC FX JAR is a recipient of a career development award from the Agency for Healthcare Research and Quality (K01 HS018088). Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: SS is principal investigator of the Brigham and Women's Hospital DEcIDE Center on Comparative Effectiveness Research and the DEcIDE Methods Center, both funded by the Agency for Healthcare Research and Quality, and of the Harvard-Brigham Drug Safety and Risk Management Research Center funded by the Food and Drug Administration; SS is a paid consultant to WHISCON LLC and Booz & Co, and he is principal investigator of investigator initiated grants to the Brigham and Women's Hospital from Pfizer, Novartis, and Boehringer-Ingelheim unrelated to the topic of this study; JAR is a paid consultant to WHISCON LLC; no other relationships or activities that could appear to have influenced the submitted work. NR 41 TC 27 Z9 28 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD SEP 19 PY 2013 VL 347 AR f5416 DI 10.1136/bmj.f5416 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 223SY UT WOS:000324831500003 PM 24052582 ER PT J AU Nishihara, R Wu, KN Lochhead, P Morikawa, T Liao, XY Qian, ZR Inamura, K Kim, SA Kuchiba, A Yamauchi, M Imamura, Y Willett, WC Rosner, BA Fuchs, CS Giovannucci, E Ogino, S Chan, AT AF Nishihara, Reiko Wu, Kana Lochhead, Paul Morikawa, Teppei Liao, Xiaoyun Qian, Zhi Rong Inamura, Kentaro Kim, Sun A. Kuchiba, Aya Yamauchi, Mai Imamura, Yu Willett, Walter C. Rosner, Bernard A. Fuchs, Charles S. Giovannucci, Edward Ogino, Shuji Chan, Andrew T. TI Long-Term Colorectal-Cancer Incidence and Mortality after Lower Endoscopy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; COLLEGE-OF-RADIOLOGY; SOCIETY TASK-FORCE; NEGATIVE COLONOSCOPY; AMERICAN-COLLEGE; SCREENING COLONOSCOPY; INTERVAL CANCERS; FAMILY-HISTORY; COLON-CANCER; RISK AB BackgroundColonoscopy and sigmoidoscopy provide protection against colorectal cancer, but the magnitude and duration of protection, particularly against cancer of the proximal colon, remain uncertain. MethodsWe examined the association of the use of lower endoscopy (updated biennially from 1988 through 2008) with colorectal-cancer incidence (through June 2010) and colorectal-cancer mortality (through June 2012) among participants in the Nurses' Health Study and the Health Professionals Follow-up Study. ResultsAmong 88,902 participants followed over a period of 22 years, we documented 1815 incident colorectal cancers and 474 deaths from colorectal cancer. With endoscopy as compared with no endoscopy, multivariate hazard ratios for colorectal cancer were 0.57 (95% confidence interval [CI], 0.45 to 0.72) after polypectomy, 0.60 (95% CI, 0.53 to 0.68) after negative sigmoidoscopy, and 0.44 (95% CI, 0.38 to 0.52) after negative colonoscopy. Negative colonoscopy was associated with a reduced incidence of proximal colon cancer (multivariate hazard ratio, 0.73; 95% CI, 0.57 to 0.92). Multivariate hazard ratios for death from colorectal cancer were 0.59 (95% CI, 0.45 to 0.76) after screening sigmoidoscopy and 0.32 (95% CI, 0.24 to 0.45) after screening colonoscopy. Reduced mortality from proximal colon cancer was observed after screening colonoscopy (multivariate hazard ratio, 0.47; 95% CI, 0.29 to 0.76) but not after sigmoidoscopy. As compared with colorectal cancers diagnosed in patients more than 5 years after colonoscopy or without any prior endoscopy, those diagnosed in patients within 5 years after colonoscopy were more likely to be characterized by the CpG island methylator phenotype (CIMP) (multivariate odds ratio, 2.19; 95% CI, 1.14 to 4.21) and microsatellite instability (multivariate odds ratio, 2.10; 95% CI, 1.10 to 4.02). ConclusionsColonoscopy and sigmoidoscopy were associated with a reduced incidence of cancer of the distal colorectum; colonoscopy was also associated with a modest reduction in the incidence of proximal colon cancer. Screening colonoscopy and sigmoidoscopy were associated with reduced colorectal-cancer mortality; only colonoscopy was associated with reduced mortality from proximal colon cancer. Colorectal cancer diagnosed within 5 years after colonoscopy was more likely than cancer diagnosed after that period or without prior endoscopy to have CIMP and microsatellite instability. C1 [Nishihara, Reiko; Lochhead, Paul; Morikawa, Teppei; Liao, Xiaoyun; Qian, Zhi Rong; Inamura, Kentaro; Kim, Sun A.; Kuchiba, Aya; Yamauchi, Mai; Imamura, Yu; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishihara, Reiko; Lochhead, Paul; Morikawa, Teppei; Liao, Xiaoyun; Qian, Zhi Rong; Inamura, Kentaro; Kim, Sun A.; Kuchiba, Aya; Yamauchi, Mai; Imamura, Yu; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Nishihara, Reiko; Wu, Kana; Kuchiba, Aya; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wu, Kana; Willett, Walter C.; Rosner, Bernard A.; Fuchs, Charles S.; Giovannucci, Edward; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Gastrointestinal Res Grp, Aberdeen, Scotland. [Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Tokyo 113, Japan. [Inamura, Kentaro] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,GRJ 825C, Boston, MA 02114 USA. EM achan@partners.org RI Kim, Sun A/L-4239-2013 OI Kim, Sun A/0000-0002-0891-2093 FU National Institutes of Health FX Funded by the National Institutes of Health and others. NR 39 TC 312 Z9 318 U1 5 U2 30 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 19 PY 2013 VL 369 IS 12 BP 1095 EP 1105 DI 10.1056/NEJMoa1301969 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 220BD UT WOS:000324554800007 PM 24047059 ER PT J AU Friedland, GH Naidoo, P Abdool-Gafoor, B Moosa, MYS Ramdial, PK Gandhi, RT AF Friedland, Gerald H. Naidoo, Pumersha Abdool-Gafoor, Bilal Moosa, Mahomed-Yunus S. Ramdial, Pratistadevi K. Gandhi, Rajesh T. TI Case 29-2013: A 32-Year-Old HIV-Positive African Man with Dyspnea and Skin Lesions SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PULMONARY KAPOSI-SARCOMA; AIDS-RELATED LYMPHOMA; IMMUNE RECONSTITUTION; SOUTH-AFRICA; RISK; TUBERCULOSIS; INFECTION; FEATURES; COHORT AB A 32-year-old man with HIV infection was admitted to a hospital in South Africa because of progressively worsening skin lesions, dyspnea, and cough. A CD4+ T-cell count was 268 per cubic millimeter. Diagnostic procedures were performed. Presentation of CaseDr. Emily K. Wong (Medicine, Massachusetts General Hospital): A 32-year-old man with human immunodeficiency virus (HIV) infection was admitted to a hospital in Durban, South Africa, because of dyspnea and cough. The hospital is associated with Massachusetts General Hospital. Five months before admission, the patient was seen in an outpatient clinic in South Africa for evaluation of a lesion on his left upper eyelid. On examination, violaceous, raised lesions were present on the left eyelid and right side of the chest (Figure 1A).Dr. Pratistadevi K. Ramdial: Pathological examination of an excisional biopsy specimen of the chest ... C1 [Friedland, Gerald H.] Yale New Haven Med Ctr, AIDS Program, New Haven, CT 06504 USA. [Friedland, Gerald H.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Friedland, Gerald H.] Yale Univ, Sch Med, Dept Epidemiol, New Haven, CT 06510 USA. [Friedland, Gerald H.] Yale Univ, Dept Med, Sch Publ Hlth, New Haven, CT 06520 USA. [Friedland, Gerald H.] Yale Univ, Sch Publ Hlth, Dept Epidemiol, New Haven, CT USA. [Naidoo, Pumersha] King Edward VIII Hosp, Dept Radiol, Durban, South Africa. [Abdool-Gafoor, Bilal; Moosa, Mahomed-Yunus S.] King Edward VIII Hosp, Dept Resp Med, Durban, South Africa. [Naidoo, Pumersha] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Radiol, Durban, South Africa. [Abdool-Gafoor, Bilal; Moosa, Mahomed-Yunus S.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Dept Resp Med, Durban, South Africa. [Abdool-Gafoor, Bilal] Inkosi Albert Luthuli Hosp, Dept Resp Med, Durban, South Africa. [Ramdial, Pratistadevi K.] Univ KwaZulu Natal, Sch Lab Med & Med Sci, Dept Anat Pathol, Durban, South Africa. [Ramdial, Pratistadevi K.] Natl Hlth Lab Serv, Durban, South Africa. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gandhi, Rajesh T.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. RP Friedland, GH (reprint author), Yale New Haven Med Ctr, AIDS Program, 20 York St, New Haven, CT 06504 USA. FU Harvard University Center for AIDS Research [NIH P30 AI060354]; McCord Hospital (Durban); University of KwaZulu-Natal; South African HIV Clinicians Society; Department of Health, KwaZulu-Natal FX Rajesh T. Gandhi, M. D., was the guest editor for this case, which was presented at the Sixth Annual Workshop on Advanced Clinical Care-AIDS in Durban, South Africa (and organized by Drs. Henry Sunpath, Mahomed-Yunus S. Moosa, Francois Venter, and Rajesh T. Gandhi). The workshop was sponsored by the Harvard University Center for AIDS Research (NIH P30 AI060354), McCord Hospital (Durban), the University of KwaZulu-Natal, the South African HIV Clinicians Society, and the Department of Health, KwaZulu-Natal. NR 29 TC 2 Z9 2 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 19 PY 2013 VL 369 IS 12 BP 1152 EP 1161 DI 10.1056/NEJMcpc1305985 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 220BD UT WOS:000324554800014 PM 24047065 ER PT J AU Awad, MM Engelman, JA Shaw, AT AF Awad, Mark M. Engelman, Jeffrey A. Shaw, Alice T. TI Acquired Resistance to Crizotinib from a Mutation in CD74-ROS1 REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Awad, Mark M.; Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Awad, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ashaw1@partners.org NR 0 TC 16 Z9 16 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 19 PY 2013 VL 369 IS 12 BP 1173 EP 1173 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 220BD UT WOS:000324554800025 PM 24047072 ER PT J AU Bender, SL Pinsky, E Sherry, NA AF Bender, Suzanne L. Pinsky, Elizabeth Sherry, Nicole A. TI Case 16-2013: A Girl with Irritability, Hypersomnia, and Somatic Symptoms REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ADOLESCENTS; CHILDREN C1 [Bender, Suzanne L.; Pinsky, Elizabeth; Sherry, Nicole A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bender, SL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 19 PY 2013 VL 369 IS 12 BP 1174 EP 1174 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 220BD UT WOS:000324554800027 PM 24047074 ER PT J AU Li, BE Gan, T Meyerson, M Rabbitts, TH Ernst, P AF Li, Bin E. Gan, Tao Meyerson, Matthew Rabbitts, Terence H. Ernst, Patricia TI Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells SO BLOOD LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; HOX GENE-EXPRESSION; HISTONE METHYLTRANSFERASE COMPLEX; TUMOR-SUPPRESSOR PROTEIN; FUSION PROTEINS; TARGET GENES; DNA-DAMAGE; LEUKEMIA; TYPE-1; TRANSCRIPTION AB Mixed Lineage Leukemia (MLL1) translocations encode fusion proteins retaining the N terminus of MLL1, which interacts with the tumor suppressor, menin. This interaction is essential for leukemogenesis and thus is a promising drugtarget. However, wild-type MLL1 plays a critical role in sustaining hematopoietic stem cells (HSCs); therefore, disruption of an essential MLL1 cofactor would be expected to obliterate normal hematopoiesis. Here we show that rather than working together as a complex, menin and MLL1 regulate distinct pathways during normal hematopoiesis, particularly in HSCs and B cells. We demonstrate the lack of genetic interaction between menin and MLL1 in steady-state or regenerative hematopoiesis and in B-cell differentiation despite the fact that MLL1 is critical for these processes. In B cells, menin-or MLL1-regulated genes can be classified into 3 categories: (1) a relatively small group of coregulated genes including previously described targets Hoxa9 and Meis1 but also Mecom and Eya1, and much larger groups of (2) exclusively menin-regulated and (3) exclusively MLL1-regulated genes. Our results highlight the large degree of independence of these 2 proteins and demonstrate that menin is not a requisite cofactor for MLL1 during normal hematopoiesis. Furthermore, our data support the development of menin-MLL1-disrupting drugs as safe and selective leukemia targeting agents. C1 [Li, Bin E.; Gan, Tao; Ernst, Patricia] Geisel Sch Med Dartmouth, Dept Genet, Hanover, NH 03755 USA. [Li, Bin E.; Gan, Tao; Ernst, Patricia] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Hanover, NH 03755 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Rabbitts, Terence H.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Haematol Unit, Oxford OX3 9DU, England. RP Ernst, P (reprint author), Geisel Sch Med Dartmouth, Dept Genet, HB 7400,Remsen 725, Hanover, NH 03755 USA. EM patricia.ernst@dartmouth.edu FU American Cancer Society [RSG-10-242-LIB]; Gabrielle's Angel Foundation for Cancer Research; Lauri Strauss Leukemia Foundation; National Institutes of Health; National Heart, Lung, and Blood Institute [HL090036]; Leukaemia and Lymphoma Research; Medical Research Council; Cancer Center Core Grant [CA23108]; National Center for Research Resources [P20-RR16437] FX This work was supported by grants from the American Cancer Society (RSG-10-242-LIB), Gabrielle's Angel Foundation for Cancer Research, Lauri Strauss Leukemia Foundation, the National Institutes of Health, National Heart, Lung, and Blood Institute (HL090036), and program grants from Leukaemia and Lymphoma Research and the Medical Research Council (T. H. R.). The Dartmouth Genomics and Microarray Laboratory received support from a Cancer Center Core Grant (CA23108), and Dartmouse was established by funding from the National Center for Research Resources (P20-RR16437). NR 50 TC 19 Z9 19 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 19 PY 2013 VL 122 IS 12 BP 2039 EP 2046 DI 10.1182/blood-2013-03-486647 PG 8 WC Hematology SC Hematology GA 224AY UT WOS:000324854800013 PM 23908472 ER PT J AU Kim, Y Chen, LC McCarley, RW Strecker, RE AF Kim, Youngsoo Chen, Lichao McCarley, Robert W. Strecker, Robert E. TI Sleep allostasis in chronic sleep restriction: The role of the norepinephrine system SO BRAIN RESEARCH LA English DT Article DE Chronic sleep restriction; Allostasis; Norepinephrine; Rat ID LOCUS-COERULEUS NEURONS; BASAL FOREBRAIN; STRESS-ULCER; RAT-BRAIN; NORADRENERGIC MODULATION; BEHAVIORAL-RESPONSE; MESSENGER-RNA; DOSE-RESPONSE; WAKING CYCLE; DEPRIVATION AB Sleep responses to chronic sleep restriction may be very different from those observed after acute total sleep deprivation. Specifically, when sleep restriction is repeated for several consecutive days, animals express attenuated compensatory increases in sleep time and intensity during daily sleep opportunities. The neurobiological mechanisms underlying these adaptive, or more specifically, allostatic, changes in sleep homeostasis are unknown. Several lines of evidence indicate that norepinephrine may play a key role in modulating arousal states and NREM EEG delta power, which is widely recognized as a marker for sleep intensity. Therefore, we investigated time course changes in brain adrenergic receptor mRNA levels in response to chronic sleep restriction using a rat model. Here, we observed that significantly altered mRNA levels of the alpha 1- adrenergic receptor in the basal forebrain as well as alpha 2- and beta 1-adrenergic receptor in the anterior cingulate cortex only on the first sleep restriction day. On the other hand, the frontal cortex alpha 1-, alpha 2-, and beta 1-adrenergic receptor mRNA levels were reduced throughout the period of sleep restriction. Combined with our earlier findings on EEG that sleep time and intensity significantly increased only on the first sleep restriction days, these results suggest that alterations in the brain norepinephrine system in the basal forebrain and cingulata cortex may mediate allostatic changes in sleep time and intensity observed during chronic sleep restriction. (c) 2013 Elsevier B.V. All rights reserved. C1 VA Boston Healthcare Syst, Res Serv, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. RP Kim, Y (reprint author), VA Boston Healthcare Syst, 940 Belmont St,151C Brockton, Brockton, MA 02301 USA. EM youngsoo_kim@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veterans Affairs [HL060292, MH039683, HL095491, NHLBI-T32 HL07901] FX This research was supported by: Department of Veterans Affairs Medical Research Service Award (RES), HL060292 (RES & RWM), MH039683 & HL095491 (RWM), NHLBI-T32 HL07901 (YK). We thank Yunren Bolortuya for technical assistance and Drs. Radhika Basheer and Ritchie E. Brown for helpful discussions. NR 61 TC 12 Z9 13 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 19 PY 2013 VL 1531 BP 9 EP 16 DI 10.1016/j.brainres.2013.07.048 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 225OJ UT WOS:000324971900002 PM 23916734 ER PT J AU Steg, PG Mehta, SR Pollack, CV Bode, C Cohen, M French, WJ Hoekstra, J Rao, SV Ruzyllo, W Ruiz-Nodar, JM Sabate, M Widimsky, P Kiss, RG Estrada, JLN Hod, H Kerkar, P Guneri, S Sezer, M Ruda, M Nicolau, JC Cavallini, C Ebrahim, I Petrov, I Kim, JH Jeong, MH Lopez, GAR Laanmets, P Kovar, F Gaudin, C Fanouillere, KC Minini, P Hoffman, EB Moryusef, A Wiviott, SD Sabatine, MS AF Steg, Philippe Gabriel Mehta, Shamir R. Pollack, Charles V., Jr. Bode, Christoph Cohen, Marc French, William J. Hoekstra, James Rao, Sunil V. Ruzyllo, Witold Ruiz-Nodar, Juan M. Sabate, Manel Widimsky, Petr Kiss, Robert Gabor Navarro Estrada, Jose Luis Hod, Hanoch Kerkar, Prafulla Guneri, Sema Sezer, Murat Ruda, Mikhail Nicolau, Jose Carlos Cavallini, Claudio Ebrahim, Iftikhar Petrov, Ivo Kim, Jae-Hyung Jeong, Myung-Ho Ramos Lopez, Gabriel Arturo Laanmets, Peep Kovar, Frantisek Gaudin, Christophe Fanouillere, Karen C. Minini, Pascal Hoffman, Elaine B. Moryusef, Angele Wiviott, Stephen D. Sabatine, Marc S. CA TAO Investigators TI Anticoagulation With Otamixaban and Ischemic Events in Non-ST-Segment Elevation Acute Coronary Syndromes The TAO Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FACTOR XA INHIBITOR; MYOCARDIAL-INFARCTION; UNFRACTIONATED HEPARIN; DOUBLE-BLIND; ANTIPLATELET THERAPIES; GLOBAL REGISTRY; INTERVENTION; EFFICACY; INSIGHTS; FONDAPARINUX AB IMPORTANCE The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial. OBJECTIVE To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, active-controlled superiority trial that enrolled 13 229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection. INTERVENTIONS Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURES The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7. RESULTS Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P=.93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P<.001). Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCE Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention. C1 [Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, F-75018 Paris, France. [Steg, Philippe Gabriel] INSERM, U698, Paris, France. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France. [Mehta, Shamir R.] McMaster Univ, Hamilton, ON, Canada. [Mehta, Shamir R.] Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada. [Pollack, Charles V., Jr.] Univ Penn, Penn Hosp, Dept Emergency Med, Philadelphia, PA 19104 USA. [Bode, Christoph] Med Univ Klin, Freiburg, Germany. [Cohen, Marc] Mt Sinai Sch Med, Newark Beth Israel Med Ctr, Div Cardiol, Newark, NJ USA. [French, William J.] Univ Calif Los Angeles, David Geffen Sch Med, Torrance, CA USA. [Hoekstra, James] Wake Forest Baptist Hlth, Winston Salem, NC USA. [Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA. [Ruzyllo, Witold] Inst Cardiol, Warsaw, Poland. [Ruiz-Nodar, Juan M.] Hosp Gen Univ Alicante, Serv Cardiol, Alicante, Spain. [Sabate, Manel] IDIBAPS, Hosp Clin, Serv Cardiol, Barcelona, Spain. [Widimsky, Petr] Charles Univ Prague, Fac Med 3, Cardioctr, Prague, Czech Republic. [Kiss, Robert Gabor] Mil Hosp, Dept Cardiol, Budapest, Hungary. [Navarro Estrada, Jose Luis] Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina. [Hod, Hanoch] Chaim Sheba Med Ctr, Leviev Heart Ctr, IL-52621 Tel Hashomer, Israel. [Kerkar, Prafulla] Seth GS Med Coll, Mumbai, Maharashtra, India. [Kerkar, Prafulla] KEM Hosp Parel, Mumbai, Maharashtra, India. [Guneri, Sema] Dokuz Eylul Univ, Fac Med, Dept Cardiol, Izmir, Turkey. [Sezer, Murat] Istanbul Univ, Istanbul Fac Med, Dept Cardiol, Istanbul, Turkey. [Ruda, Mikhail] Cardiol Res Ctr, Cardiovasc Div, Moscow 121552, Russia. [Nicolau, Jose Carlos] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. [Cavallini, Claudio] Osped Santa Maria Misericordia, Perugia, Italy. [Ebrahim, Iftikhar] Netcare Unitas Hosp, Centurion, Gauteng, South Africa. [Petrov, Ivo] Tokuda Hosp, Clin Cardiol & Angiol, Sofia, Bulgaria. [Kim, Jae-Hyung] Catholic Univ Korea, Coll Med, Dept Cardiol, Seoul, South Korea. [Jeong, Myung-Ho] Chonnam Natl Univ Hosp, Kwangju, South Korea. [Ramos Lopez, Gabriel Arturo] Hosp Civil Dr Juan I Menchaca, Guadalajara, Jalisco, Mexico. [Laanmets, Peep] North Estonia Med Ctr Fdn, Tallinn, Estonia. [Kovar, Frantisek] Univ Hosp, Internal Clin, Martin, Slovenia. [Gaudin, Christophe; Fanouillere, Karen C.; Minini, Pascal] Sanofi R&D, Paris, France. [Moryusef, Angele] Sanofi, Bridgewater, NJ USA. [Hoffman, Elaine B.; Wiviott, Stephen D.; Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. RP Steg, PG (reprint author), Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE, 46 Rue Henri Huchard, F-75018 Paris, France. EM gabriel.steg@bch.aphp.fr RI Nicolau, Jose/E-1487-2012; Manolis, Antonis/F-5003-2014; Widimsky, Petr/P-8088-2016 OI Widimsky, Petr/0000-0001-5686-7752 FU sanofi FX This trial was funded by sanofi. NR 28 TC 17 Z9 18 U1 0 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 18 PY 2013 VL 310 IS 11 BP 1145 EP 1155 DI 10.1001/jama.2013.277165 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 219IU UT WOS:000324500300021 PM 23995608 ER PT J AU Huang, MQ Kantardzhieva, A Scheffer, D Liberman, MC Chen, ZY AF Huang, Mingqian Kantardzhieva, Albena Scheffer, Deborah Liberman, M. Charles Chen, Zheng-Yi TI Hair Cell Overexpression of Islet1 Reduces Age-Related and Noise-Induced Hearing Loss SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MOTOR-NEURON; INTERNEURON IDENTITY; F1-HYBRID STRAINS; TRANSGENIC MICE; HOMEOBOX GENES; GANGLION-CELL; MOUSE COCHLEA; C57BL/6 MICE; INNER-EAR; ISL1 AB Isl1 is a LIM-homeodomain transcription factor that is critical in the development and differentiation of multiple tissues. In the mouse inner ear, Isl1 is expressed in the prosensory region of otocyst, in young hair cells and supporting cells, and is no longer expressed in postnatal auditory hair cells. To evaluate how continuous Isl1 expression in postnatal hair cells affects hair cell development and cochlear function, we created a transgenic mouse model in which the Pou4f3 promoter drives Isl1 overexpression specifically in hair cells. Isl1 overexpressing hair cells develop normally, as seen by morphology and cochlear functions (auditory brainstem response and otoacoustic emissions). As the mice aged to 17 months, wild-type (WT) controls showed the progressive threshold elevation and outer hair cell loss characteristic of the age-related hearing loss (ARHL) in the background strain (C57BL/6J). In contrast, the Isl1 transgenic mice showed significantly less threshold elevation with survival of hair cells. Further, the Isl1 overexpression protected the ear from noise-induced hearing loss (NIHL): both ABR threshold shifts and hair cell death were significantly reduced when compared with WT littermates. Our model suggests a common mechanism underlying ARHL and NIHL, and provides evidence that hair cell-specific Isl1 expression can promote hair cell survival and therefore minimize the hearing impairment that normally occurs with aging and/or acoustic overexposure. C1 [Huang, Mingqian; Kantardzhieva, Albena; Scheffer, Deborah; Liberman, M. Charles; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Huang, Mingqian; Kantardzhieva, Albena; Scheffer, Deborah; Liberman, M. Charles; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Scheffer, Deborah] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Scheffer, Deborah] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Chen, ZY (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM zheng-yi_chen@meei.harvard.edu OI Scheffer, Deborah/0000-0002-6066-5907 FU National Institutes of Health [R01 DC06908, R01 DC 00188, P30 DC 05029]; Capita Foundation; Ellison Foundation; Fredrick and Ines Yeatts Inner Ear Hair Cell Regeneration Fellowship; Bertarelli Foundation FX This work was supported by National Institutes of Health grants (R01 DC06908 to Z.-Y.C., R01 DC 00188 to M. C. L., and P30 DC 05029 to M. C. L.), a grant from the Capita Foundation (Z.-Y.C.), a grant from the Ellison Foundation (Z.-Y.C.), by the Fredrick and Ines Yeatts Inner Ear Hair Cell Regeneration Fellowship to M. H. and A. K., and by a grant from the Bertarelli Foundation (Z.-Y.C.). NR 52 TC 7 Z9 8 U1 2 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 18 PY 2013 VL 33 IS 38 BP 15086 EP 15094 DI 10.1523/JNEUROSCI.1489-13.2013 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 220LW UT WOS:000324586500015 PM 24048839 ER PT J AU Kalilani-Phiri, L Thesing, PC Nyirenda, OM Mawindo, P Madanitsa, M Membe, G Wylie, B Masonbrink, A Makwakwa, K Kamiza, S Muehlenbachs, A Taylor, TE Laufer, MK AF Kalilani-Phiri, Linda Thesing, Phillip C. Nyirenda, Osward M. Mawindo, Patricia Madanitsa, Mwayi Membe, Gladys Wylie, Blair Masonbrink, Abbey Makwakwa, Kingsley Kamiza, Steve Muehlenbachs, Atis Taylor, Terrie E. Laufer, Miriam K. TI Timing of Malaria Infection during Pregnancy Has Characteristic Maternal, Infant and Placental Outcomes SO PLOS ONE LA English DT Article ID PLASMODIUM-FALCIPARUM INFECTIONS; BIRTH-WEIGHT; ANEMIA AB We conducted a clinical study of pregnant women in Blantyre, Malawi to determine the effect of the timing of malaria infection during pregnancy on maternal, infant and placental outcomes. Women were enrolled in their first or second trimester of their first or second pregnancy and followed every four weeks until delivery. Three doses of sulfadoxine-pyrimethamine were given for intermittent preventive treatment for malaria, and all episodes of parasitemia were treated according to the national guidelines. Placentas were collected at delivery and examined for malaria parasites and pigment by histology. Pregnant women had 0.6 episodes of malaria per person year of follow up. Almost all episodes of malaria were detected at enrollment and malaria infection during the follow up period was rare. Malaria and anemia at the first antenatal visit were independently associated with an increased risk of placental malaria detected at delivery. When all episodes of malaria were treated with effective antimalarial medication, only peripheral malaria infection at the time of delivery was associated with adverse maternal and infant outcomes. One quarter of the analyzed placentas had evidence of malaria infection. Placental histology was 78% sensitive and 89% specific for peripheral malaria infection during pregnancy. This study suggests that in this setting of high antifolate drug resistance, three doses of sulfadoxine-pyrimethamine maintain some efficacy in suppressing microscopically detectable parasitemia, although placental infection remains frequent. Even in this urban setting, a large proportion of women have malaria infection at the time of their first antenatal care visit. Interventions to control malaria early and aggressive case detection are required to limit the detrimental effects of pregnancy-associated malaria. C1 [Kalilani-Phiri, Linda] Univ Malawi, Coll Med, Dept Community Heath, Blantyre, Malawi. [Thesing, Phillip C.; Nyirenda, Osward M.; Mawindo, Patricia; Madanitsa, Mwayi; Taylor, Terrie E.] Univ Malawi, Coll Med, Blantyre Malaria Project, Blantyre, Malawi. [Membe, Gladys] Univ Malawi, Coll Med, Dept Obstet & Gynaecol, Blantyre, Malawi. [Wylie, Blair] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Masonbrink, Abbey] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. [Makwakwa, Kingsley; Kamiza, Steve] Univ Malawi, Coll Med, Dept Histopathol, Blantyre, Malawi. [Muehlenbachs, Atis] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Taylor, Terrie E.] Michigan State Univ, Coll Osteopath Med, Dept Internal Med, E Lansing, MI 48824 USA. [Laufer, Miriam K.] Univ Maryland, Sch Med, Ctr Vaccine Dev HHMI, Baltimore, MD 21201 USA. RP Laufer, MK (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev HHMI, Baltimore, MD 21201 USA. EM mlaufer@medicine.umaryland.edu FU Doris Duke Charitable Foundation [CSDA 081072]; National Institute of Allergy and Infectious Diseases, National Institutes of Health [K23AI059316, R34AI079315, U01AI087624]; Howard Hughes Medical Institute FX This work was funded by the Doris Duke Charitable Foundation (CSDA 081072); National Institute of Allergy and Infectious Diseases, National Institutes of Health (K23AI059316, R34AI079315, U01AI087624; and Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 12 TC 13 Z9 13 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 18 PY 2013 VL 8 IS 9 AR e74643 DI 10.1371/journal.pone.0074643 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 221YD UT WOS:000324695900073 PM 24058614 ER PT J AU Comeau, DC Dogan, RI Ciccarese, P Cohen, KB Krallinger, M Leitner, F Lu, ZY Peng, YF Rinaldi, F Torii, M Valencia, A Verspoor, K Wiegers, TC Wu, CH Wilbur, WJ AF Comeau, Donald C. Dogan, Rezarta Islamaj Ciccarese, Paolo Cohen, Kevin Bretonnel Krallinger, Martin Leitner, Florian Lu, Zhiyong Peng, Yifan Rinaldi, Fabio Torii, Manabu Valencia, Alfonso Verspoor, Karin Wiegers, Thomas C. Wu, Cathy H. Wilbur, W. John TI BioC: a minimalist approach to interoperability for biomedical text processing SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID COMPARATIVE TOXICOGENOMICS DATABASE; INFORMATION EXTRACTION; RESOURCE; BIOLOGY AB A vast amount of scientific information is encoded in natural language text, and the quantity of such text has become so great that it is no longer economically feasible to have a human as the first step in the search process. Natural language processing and text mining tools have become essential to facilitate the search for and extraction of information from text. This has led to vigorous research efforts to create useful tools and to create humanly labeled text corpora, which can be used to improve such tools. To encourage combining these efforts into larger, more powerful and more capable systems, a common interchange format to represent, store and exchange the data in a simple manner between different language processing systems and text mining tools is highly desirable. Here we propose a simple extensible mark-up language format to share text documents and annotations. The proposed annotation approach allows a large number of different annotations to be represented including sentences, tokens, parts of speech, named entities such as genes or diseases and relationships between named entities. In addition, we provide simple code to hold this data, read it from and write it back to extensible mark-up language files and perform some sample processing. We also describe completed as well as ongoing work to apply the approach in several directions. C1 [Comeau, Donald C.; Dogan, Rezarta Islamaj; Lu, Zhiyong; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Ciccarese, Paolo] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ciccarese, Paolo] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Cohen, Kevin Bretonnel] Univ Colorado Denver, Sch Med, Ctr Computat Pharmacol, Aurora, CO 80045 USA. [Krallinger, Martin; Leitner, Florian; Valencia, Alfonso] Spanish Natl Canc Res Ctr, Struct & Computat Biol Grp, E-28029 Madrid, Spain. [Peng, Yifan; Torii, Manabu; Wu, Cathy H.] Univ Delaware, Dept Comp & Informat Sci, Ctr Bioinformat & Computat Biol, Newark, DE 19711 USA. [Rinaldi, Fabio] Univ Zurich, Inst Computat Linguist, CH-8050 Zurich, Switzerland. [Verspoor, Karin] Univ Melbourne, Victoria Res Lab, Natl ICT Australia NICTA, Parkville, Vic 3010, Australia. [Wiegers, Thomas C.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. RP Dogan, RI (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM Rezarta.Islamaj@nih.gov RI Valencia, Alfonso/I-3127-2015; Verspoor, Karin/G-6034-2016; Peng, Yifan/M-1605-2016; OI Valencia, Alfonso/0000-0002-8937-6789; Rinaldi, Fabio/0000-0001-5718-5462; Verspoor, Karin/0000-0002-8661-1544; Peng, Yifan/0000-0001-9309-8331; Leitner, Florian/0000-0003-4458-504X; Torii, Manabu/0000-0002-4825-0696 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine; National Library of Medicine [G08LM010720]; National Institutes of Health [NIH 5R01 LM009254-07, NIH 5R01 LM008111-08]; National Science Foundation [DBI-1062520]; Swiss National Science Foundation [105315_130558/1] FX Intramural Research Program of the National Institutes of Health, National Library of Medicine to D. C. C., R. I. D., Z.L. and W.J.W; National Library of Medicine [G08LM010720] to C. H. W.; National Institutes of Health [NIH 5R01 LM009254-07, NIH 5R01 LM008111-08] to K. B. C.; National Science Foundation [DBI-1062520] to Y.P., M. T. and C. H. W.; and Swiss National Science Foundation [105315_130558/1] to F.R. NR 64 TC 12 Z9 12 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD SEP 18 PY 2013 AR bat064 DI 10.1093/database/bat064 PG 15 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 220XL UT WOS:000324620500001 ER PT J AU Leentjens, AFG Moonen, AJH Dujardin, K Marsh, L Martinez-Martin, P Richard, IH Starkstein, SE Kohler, S AF Leentjens, Albert F. G. Moonen, Anja J. H. Dujardin, Kathy Marsh, Laura Martinez-Martin, Pablo Richard, Irene H. Starkstein, Sergio E. Kohler, Sebastian TI Modeling depression in Parkinson disease Disease-specific and nonspecific risk factors SO NEUROLOGY LA English DT Article ID QUALITY-OF-LIFE; RATING-SCALES; ANXIETY; RECOMMENDATIONS; PREVALENCE; VALIDATION; DEMENTIA; MARKERS; MINI AB Objective: To construct a model for depression in Parkinson disease (PD) and to study the relative contribution of PD-specific and nonspecific risk factors to this model. Methods: Structural equation modeling of direct and indirect associations of risk factors with the latent depression outcome using a cross-sectional dataset of 342 patients with PD. Results: A model with acceptable fit was generated that explained 41% of the variance in depression. In the final model, 3 PD-specific variables (increased disease duration, more severe motor symptoms, the use of levodopa) and 6 nonspecific variables (female sex, history of anxiety and/or depression, family history of depression, worse functioning on activities of daily living, and worse cognitive status) were maintained and significantly associated with depression. Nonspecific risk factors had a 3-times-higher influence in the model than PD-specific risk factors. Conclusion: In this cross-sectional study, we showed that nonspecific factors may be more prominent markers of depression than PD-specific factors. Accordingly, research on depression in PD should focus not only on factors associated with or specific for PD, but should also examine a wider scope of factors including general risk factors for depression, not specific for PD. C1 [Leentjens, Albert F. G.; Moonen, Anja J. H.] Maastricht Univ, Med Ctr, Dept Psychiat, Maastricht, Netherlands. [Leentjens, Albert F. G.; Moonen, Anja J. H.; Kohler, Sebastian] Maastricht Univ, Sch Mental Hlth & Neurosci, Maastricht, Netherlands. [Dujardin, Kathy] Univ Lille, Med Ctr, Neurol & Movement Disorders Unit, Lille, France. [Marsh, Laura] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Martinez-Martin, Pablo] Carlos III Inst Hlth, Alzheimer Ctr Reina Sofia Fdn, Alzheimer Dis Res Unit, Madrid, Spain. [Martinez-Martin, Pablo] Carlos III Inst Hlth, Alzheimer Ctr Reina Sofia Fdn, CIBERNED, Madrid, Spain. [Richard, Irene H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Richard, Irene H.] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. [Starkstein, Sergio E.] Univ Western Australia, Sch Psychiat, Fremantle, WA, Australia. [Starkstein, Sergio E.] Fremantle Hosp, Fremantle, WA, Australia. RP Leentjens, AFG (reprint author), Maastricht Univ, Med Ctr, Dept Psychiat, Maastricht, Netherlands. EM a.leentjens@maastrichtuniversity.nl FU Michael J. Fox Foundation for Parkinson's Research FX This study did not receive any funding. The study on which database this analysis was performed received funding from the Michael J. Fox Foundation for Parkinson's Research. NR 32 TC 11 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 17 PY 2013 VL 81 IS 12 BP 1036 EP 1043 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EK UT WOS:000330767900007 PM 23946309 ER PT J AU Singhal, AB Biller, J Elkind, MS Fullerton, HJ Jauch, EC Kittner, SJ Levine, DA Levine, SR AF Singhal, Aneesh B. Biller, Jose Elkind, Mitchell S. Fullerton, Heather J. Jauch, Edward C. Kittner, Steven J. Levine, Deborah A. Levine, Steven R. TI Recognition and management of stroke in young adults and adolescents SO NEUROLOGY LA English DT Review ID 1ST-EVER ISCHEMIC-STROKE; PATENT FORAMEN OVALE; TERM-FOLLOW-UP; RISK-FACTORS; INTRAVENOUS THROMBOLYSIS; PEDIATRIC STROKE; CARDIOVASCULAR-DISEASE; CEREBRAL INFARCTION; CRYPTOGENIC STROKE; CHILDHOOD STROKE AB Approximately 15% of all ischemic strokes (IS) occur in young adults and adolescents. To date, only limited prior public health and research efforts have specifically addressed stroke in the young. Early diagnosis remains challenging because of the lack of awareness and the relative infrequency of stroke compared with stroke mimics. Moreover, the causes of IS in the young are heterogeneous and can be relatively uncommon, resulting in uncertainties about diagnostic evaluation and cause-specific management. Emerging data have raised public health concerns about the increasing prevalence of traditional vascular risk factors in young individuals, and their potential role in increasing the risk of IS, stroke recurrence, and poststroke mortality. These issues make it important to formulate and enact strategies to increase both awareness and access to resources for young stroke patients, their caregivers and families, and health care professionals. The American Academy of Neurology recently convened an expert panel to develop a consensus document concerning the recognition, evaluation, and management of IS in young adults and adolescents. The report of the consensus panel is presented herein. C1 [Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Biller, Jose] Loyola Univ Chicago, Dept Neurol, Maywood, IL USA. [Elkind, Mitchell S.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Elkind, Mitchell S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Fullerton, Heather J.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Fullerton, Heather J.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Jauch, Edward C.] Med Univ S Carolina, Div Emergency Med, Charleston, SC USA. [Jauch, Edward C.] Med Univ S Carolina, Dept Neurosci, Charleston, SC USA. [Kittner, Steven J.] Baltimore Vet Adm Med Ctr, Dept Neurol, Baltimore, MD USA. [Kittner, Steven J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Levine, Deborah A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Levine, Deborah A.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Levine, Deborah A.] Ann Arbor VA Med Ctr, Ann Arbor, MI USA. [Levine, Steven R.] SUNY Downstate Coll Med & Med Ctr, Dept Neurol, Brooklyn, NY USA. [Levine, Steven R.] SUNY Downstate Coll Med & Med Ctr, Dept Emergency Med, Brooklyn, NY USA. [Levine, Steven R.] Kings Cty Hosp Ctr, Brooklyn, NY USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM asinghal@partners.org FU NIH; Pfizer, Inc.; Photothera, Inc.; diaDexus Inc.; Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; American Heart Association; National Institute of Neurological Disorders and Stroke (NINDS); Novo Nordisk; Genentech; Office of Research and Development; Medical Research Service; Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; NINDS [U01 NS069208-01]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK092926]; National Institute of Aging [K23AG040278]; PCORI FX A. Singhal receives research support from NIH; serves as site investigator in clinical trials sponsored by Pfizer, Inc. and Photothera, Inc.; is a consultant for Biogen-Idec, Inc., serves on event adjudication committees for the TIMI Study Group; has served as a medical expert witness in individual cases concerning stroke in young adults; is Associate Editor for the journal Medical Gas Research; and his wife is an employee of Biogen-Idec, Inc. and holds stock in Biogen-Idec, Inc. and Vertex Pharmaceuticals, Inc. J. Biller serves as Editor of the Journal of Stroke and Cerebrovascular Diseases and Chief Editor of Frontiers in Neurology. M. Elkind receives research support from diaDexus Inc., Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, and the NIH; serves on an event adjudication committee for Jarvik Heart; has received compensation for consulting from Biogen-Idec, Inc. and BMS-Pfizer Partnership, and for participation in litigation on behalf of Novartis, Organon, and GlaxoSmithKline; and receives compensation from the American Academy of Neurology for service as Resident and Fellow Section Editor for the journal Neurology (R). H. Fullerton receives research support from the NIH and American Heart Association. E. Jauch reports research support from the National Institute of Neurological Disorders and Stroke (NINDS), Novo Nordisk, and Genentech, and serves as a consultant to Genentech. S. Kittner was supported by the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs, and by a grant from NINDS (U01 NS069208-01). D. Levine was supported by grant P30DK092926 from the National Institute of Diabetes and Digestive and Kidney Diseases (investigator) and by grant K23AG040278 (D. Levine PI) from the National Institute of Aging, and serves as a consultant (cardiovascular event adjudicator) on the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial (NINDS 1U01S062835; Johnston SC/Easton JD, multiple PIs). S. Levine has previously served on the advisory board of Genentech, Inc. (honorarium donated to stroke research), is Associate Editor of MEDLINK, receives research funding from the NIH, PCORI, and Genentech, and has served as an expert witness in stroke cases including stroke in the young. Go to Neurology.org for full disclosures. NR 60 TC 27 Z9 28 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 17 PY 2013 VL 81 IS 12 BP 1089 EP 1097 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EK UT WOS:000330767900015 PM 23946297 ER PT J AU Ginat, DT Rastalsky, N AF Ginat, Daniel Thomas Rastalsky, Naina TI Teaching NeuroImages: Polymyalgia rheumatica and giant cell arteritis SO NEUROLOGY LA English DT Editorial Material C1 [Ginat, Daniel Thomas] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Rastalsky, Naina] Massachusetts Gen Hosp, Dept Rheumatol, Boston, MA 02114 USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 17 PY 2013 VL 81 IS 12 BP E96 EP E96 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EK UT WOS:000330767900003 PM 24042579 ER PT J AU Neve, KA Ford, CP Buck, DC Grandy, DK Neve, RL Phillips, TJ AF Neve, K. A. Ford, C. P. Buck, D. C. Grandy, D. K. Neve, R. L. Phillips, T. J. TI NORMALIZING DOPAMINE D2 RECEPTOR-MEDIATED RESPONSES IN D2 NULL MUTANT MICE BY VIRUS-MEDIATED RECEPTOR RESTORATION: COMPARING D2(L) AND D2(S) SO NEUROSCIENCE LA English DT Article DE dopamine D2 receptor; methamphetamine; D2 receptor null mutant mouse; potassium channel ID DEFICIENT MICE; AUTORECEPTOR FUNCTION; D2-DOPAMINE RECEPTOR; IN-VIVO; ISOFORMS; NEURONS; EXPRESSION; METHAMPHETAMINE; STIMULATION; FORMS AB D2 receptor null mutant (Drd2(-/-)) mice have altered responses to the rewarding and locomotor effects of psychostimulant drugs, which is evidence of a necessary role for D2 receptors in these behaviors. Furthermore, work with mice that constitutively express only the D2 receptor short form (D2(S)), as a result of genetic deletion of the long form (D2(L)), provides the basis for a current model in which D2(L) is thought to be the postsynaptic D2 receptor on medium spiny neurons in the basal forebrain, and D2(S) the autoreceptor that regulates the activity of dopamine neurons and dopamine synthesis and release. Because constitutive genetic deletion of the D2 or D2(L) receptor may cause compensatory changes that influence functional outcomes, our approach is to identify aspects of the abnormal phenotype of a Drd2(-/-) mouse that can be normalized by virus-mediated D2 receptor expression. Drd2(-/-) mice are deficient in basal and methamphetamine-induced locomotor activation and lack D2 receptor agonist-induced activation of G protein-regulated inward rectifying potassium channels (GIRKs) in dopaminergic neurons. Here we show that virus-mediated expression of D2(L) in the nucleus accumbens significantly restored methamphetamine-induced locomotor activation, but not basal locomotor activity, compared to mice receiving the control virus. It also restored the effect of methamphetamine to decrease time spent in the center of the activity chamber in female but not male Drd2(-/-) mice. Furthermore, the effect of expression of D2(S) was indistinguishable from D2(L). Similarly, virus-mediated expression of either D2(S) or D2(L) in substantia nigra neurons restored D2 agonist-induced activation of GIRKs. In this acute expression system, the alternatively spliced forms of the D2 receptor appear to be equally capable of acting as postsynaptic receptors and autoreceptors. Published by Elsevier Ltd. on behalf of IBRO. C1 [Neve, K. A.; Buck, D. C.; Phillips, T. J.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Neve, K. A.; Buck, D. C.; Phillips, T. J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Neve, K. A.; Buck, D. C.; Phillips, T. J.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA. [Ford, C. P.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA. [Grandy, D. K.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Neve, R. L.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Neve, KA (reprint author), VA Med Ctr, Res Serv R&D 30, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM nevek@ohsu.edu; cpf21@case.edu; buckd@ohsu.edu; grandyd@ohsu.edu; rneve@MIT.EDU; phillipt@ohsu.edu FU NIH [MH045372, DA018165, DA026416]; VA Merit Review program; Career Scientist program FX This work was support by NIH Grants MH045372, DA018165, and DA026416, and the VA Merit Review and Career Scientist programs. NR 33 TC 7 Z9 7 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD SEP 17 PY 2013 VL 248 BP 479 EP 487 DI 10.1016/j.neuroscience.2013.06.035 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 299UV UT WOS:000330422100044 PM 23811070 ER PT J AU Zhao, X Huang, H Chen, Y Liu, Y Zhang, Z Ma, Q Qiu, M AF Zhao, X. Huang, H. Chen, Y. Liu, Y. Zhang, Z. Ma, Q. Qiu, M. TI DYNAMIC EXPRESSION OF SECRETED FRIZZLED-RELATED PROTEIN 3 (sFRP3) IN THE DEVELOPING MOUSE SPINAL CORD AND DORSAL ROOT GANGLIA SO NEUROSCIENCE LA English DT Article DE secreted Frizzled-related protein 3; spinal cord; dorsal root ganglia sensory circuit ID WNT SIGNALING PATHWAY; SPEMANN ORGANIZER; NERVOUS-SYSTEM; RECEPTOR; FRZB-1; FAMILY; TISSUE; BINDING; MORPHOGENESIS; NEUROGENESIS AB Wnt proteins have been implicated in regulating a variety of developmental processes in the CNS. Secreted Frizzled-related protein 3 (sFRP3) is a member of the sFRP family that can inhibit the Wnt signaling by binding directly to Wnts via their regions of homology to the Wnt-binding domain of Frizzleds. Recent studies suggested that sFRP3 plays an important role in cell proliferation and differentiation in various tissues. To understand the role of sFRP3 in neural development, we carried out detailed studies on the expression of sFRP3 in the developing nervous system. Our results revealed that sFRP3 is initially expressed in the ventricular zone of the spinal cord and dorsal root ganglia (DRG), and later in the dorsal horn of spinal cord and subpopulation of DRG neurons. The spatiotemporally dynamic expression of sFRP3 strongly suggests that sFRP3 has potential functions in the sensory neuron genesis and sensory circuitry formation. Published by Elsevier Ltd. on behalf of IBRO. C1 [Zhao, X.; Huang, H.; Chen, Y.; Liu, Y.; Zhang, Z.; Qiu, M.] Hangzhou Normal Univ, Inst Dev & Regenerat Biol, Coll Life & Environm Sci, Hangzhou 310029, Zhejiang, Peoples R China. [Ma, Q.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Ma, Q.] Harvard Univ, Dept Neurobiol, Sch Med, Boston, MA 02115 USA. [Qiu, M.] Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA. RP Qiu, M (reprint author), Hangzhou Normal Univ, Inst Dev & Regenerat Biol, Coll Life & Environm Sci, Hangzhou 310029, Zhejiang, Peoples R China. EM m0qiu001@yahoo.com FU National Key Basic Research Program of China [2013CB531300]; National Natural Sciences Foundation of China [31000488, 31071879]; Zhejiang Provincial Natural Science Foundation of China [Z2100730]; Major Project of Science and Technology Department of Zhejiang Province [2011C13030]; NIH [R01NS37717] FX The National Key Basic Research Program of China (2013CB531300), National Natural Sciences Foundation of China (Grant Nos: 31000488; 31071879), Zhejiang Provincial Natural Science Foundation of China (Z2100730) and Major Project of Science and Technology Department of Zhejiang Province (2011C13030). NIH (R01NS37717). NR 41 TC 2 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD SEP 17 PY 2013 VL 248 BP 594 EP 601 DI 10.1016/j.neuroscience.2013.06.044 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 299UV UT WOS:000330422100053 PM 23827310 ER PT J AU Red Brewer, M Yun, CH Lai, D Lemmon, MA Eck, MJ Pao, W AF Red Brewer, Monica Yun, Cai-Hong Lai, Darson Lemmon, Mark A. Eck, Michael J. Pao, William TI Mechanism for activation of mutated epidermal growth factor receptors in lung cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mutation; TKI; lapatinib; WZ-4002 ID EGFR KINASE DOMAIN; WILD-TYPE RAS; TYROSINE KINASE; ACQUIRED-RESISTANCE; INHIBITOR; MUTATIONS; GEFITINIB; SENSITIVITY; ERLOTINIB; INSIGHTS AB The initiation of epidermal growth factor receptor (EGFR) kinase activity proceeds via an asymmetric dimerization mechanism in which a "donor" tyrosine kinase domain (TKD) contacts an "acceptor" TKD, leading to its activation. In the context of a ligand-induced dimer, identical wild-type EGFR TKDs are thought to assume the donor or acceptor roles in a random manner. Here, we present biochemical reconstitution data demonstrating that activated EGFR mutants found in lung cancer preferentially assume the acceptor role when coexpressed with WT EGFR. Mutated EGFRs show enhanced association with WT EGFR, leading to hyperphosphorylation of the WT counterpart. Mutated EGFRs also hyperphosphorylate the related erythroblastic leukemia viral oncogene (ErbB) family member, ErbB-2, in a similar manner. This directional "superacceptor activity" is particularly pronounced in the drug-resistant L834R/T766M mutant. A 4-angstrom crystal structure of this mutant in the active conformation reveals an asymmetric dimer interface that is essentially the same as that in WT EGFR. Asymmetric dimer formation induces an allosteric conformational change in the acceptor subunit. Thus, superacceptor activity likely arises simply from a lower energetic cost associated with this conformational change in the mutant EGFR compared with WT, rather than from any structural alteration that impairs the donor role of the mutant. Collectively, these findings define a previously unrecognized mode of mutant-specific intermolecular regulation for ErbB receptors, knowledge of which could potentially be exploited for therapeutic benefit. C1 [Red Brewer, Monica; Lai, Darson; Pao, William] Vanderbilt Univ, Dept Med, Div Hematol Oncol, Nashville, TN 37232 USA. [Yun, Cai-Hong; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Yun, Cai-Hong; Eck, Michael J.] Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. [Yun, Cai-Hong; Eck, Michael J.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Lemmon, Mark A.] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Pao, W (reprint author), Vanderbilt Univ, Dept Med, Div Hematol Oncol, Nashville, TN 37232 USA. EM william.pao@vanderbilt.edu OI Lemmon, Mark/0000-0002-3379-5319 FU V Foundation; National Cancer Institute [R01-CA121210, P01-CA129243, U54-CA143798, R01-CA116020, P01-CA154303, R01-CA079992]; Vanderbilt Unversity [CA90949]; Vanderbilt-Ingram Cancer Center Core Grant [P30-CA68485] FX We acknowledge Graham Carpenter and members of the W. P. laboratory for fruitful discussions and Jin H. Park for efforts in further analysis of the mutated EGFRs. This work was supported in part by grants from the V Foundation (to W. P.) and the National Cancer Institute [R01-CA121210, P01-CA129243, and U54-CA143798 (to W. P.); R01-CA116020 and P01-CA154303 (to M.J.E.); and R01-CA079992 (to M. A. L.)]. W. P. received additional support from Vanderbilt Unversity's Specialized Program of Research Excellence in Lung Cancer, Grant CA90949 and the Vanderbilt-Ingram Cancer Center Core Grant, P30-CA68485. NR 41 TC 19 Z9 20 U1 0 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 17 PY 2013 VL 110 IS 38 BP E3595 EP E3604 DI 10.1073/pnas.1220050110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219GW UT WOS:000324495300010 PM 24019492 ER PT J AU Rosenberg, SM Tracy, MS Meyer, ME Sepucha, K Gelber, S Hirshfield-Bartek, J Troyan, S Morrow, M Schapira, L Come, SE Winer, EP Partridge, AH AF Rosenberg, Shoshana M. Tracy, Michaela S. Meyer, Meghan E. Sepucha, Karen Gelber, Shari Hirshfield-Bartek, Judi Troyan, Susan Morrow, Monica Schapira, Lidia Come, Steven E. Winer, Eric P. Partridge, Ann H. TI Perceptions, Knowledge, and Satisfaction With Contralateral Prophylactic Mastectomy Among Young Women With Breast Cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; BRCA2 MUTATION CARRIERS; CARCINOMA IN-SITU; LOCOREGIONAL RECURRENCE; RANDOMIZED-TRIAL; DECISION-MAKING; FAMILY-HISTORY; PERCEIVED RISK; SURGERY; PREDICTORS AB Background: Rates of contralateral prophylactic mastectomy (CPM) have increased dramatically, particularly among younger women with breast cancer, but little is known about how women approach the decision to have CPM. Objective: To examine preferences, knowledge, decision making, and experiences of young women with breast cancer who choose CPM. Design: Cross-sectional survey. Setting: 8 academic and community medical centers that enrolled 550 women diagnosed with breast cancer at age 40 years or younger between November 2006 and November 2010. Patients: 123 women without known bilateral breast cancer who reported having bilateral mastectomy. Measurements: A 1-time, 23-item survey that included items related to decision making, knowledge, risk perception, and breast cancer worry. Results: Most women indicated that desires to decrease their risk for contralateral breast cancer (98%) and improve survival (94%) were extremely or very important factors in their decision to have CPM. However, only 18% indicated that women with breast cancer who undergo CPM live longer than those who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk for contralateral breast cancer, whereas women without a known mutation substantially overestimated this risk. Limitations: The survey, which was administered a median of 2 years after surgery, was not validated, and some questions might have been misinterpreted by respondents or subject to recall bias. Generalizability of the findings might be limited. Conclusion: Despite knowing that CPM does not clearly improve survival, women who have the procedure do so, in part, to extend their lives. Many women overestimate their actual risk for cancer in the unaffected breast. Interventions aimed at improving risk communication in an effort to promote evidence- based decision making are warranted. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Massachusetts Gen Hosp,Sch Publ Hlth, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, D1210,450 Brookline Ave, Boston, MA 02115 USA. EM ahpartridge@partners.org FU National Cancer Institute [NIH 5 R25 CA057711] FX Dr. Partridge and the YWS receive support from Susan G. Komen for the Cure. Dr. Rosenberg receives support from the National Cancer Institute (NIH 5 R25 CA057711). NR 50 TC 79 Z9 79 U1 0 U2 17 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 17 PY 2013 VL 159 IS 6 BP 373 EP + DI 10.7326/0003-4819-159-6-201309170-00003 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 234EY UT WOS:000325625900013 PM 24042365 ER PT J AU Humphrey, LL Deffebach, M Pappas, M Baumann, C Artis, K Mitchell, JP Zakher, B Fu, RW Slatore, CG AF Humphrey, Linda L. Deffebach, Mark Pappas, Miranda Baumann, Christina Artis, Kathryn Mitchell, Jennifer Priest Zakher, Bernadette Fu, Rongwei Slatore, Christopher G. TI Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U. S. Preventive Services Task Force Recommendation SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID 2-YEAR FOLLOW-UP; SMOKING-CESSATION; SPIRAL CT; RANDOMIZED FEASIBILITY; CUMULATIVE INCIDENCE; CHEST RADIOGRAPH; FORMER SMOKERS; ITALUNG TRIAL; DANTE TRIAL; RISK AB Background: Lung cancer is the leading cause of cancer-related death in the United States. Because early-stage lung cancer is associated with lower mortality than late-stage disease, early detection and treatment may be beneficial. Purpose: To update the 2004 review of screening for lung cancer for the U.S. Preventive Services Task Force, focusing on screening with low-dose computed tomography (LDCT). Data Sources: MEDLINE (2000 to 31 May 2013), the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2012), Scopus, and reference lists. Study Selection: English-language randomized, controlled trials or cohort studies that evaluated LDCT screening for lung cancer. Data Extraction: One reviewer extracted study data about participants, design, analysis, follow-up, and results, and a second reviewer checked extractions. Two reviewers rated study quality using established criteria. Data Synthesis: Four trials reported results of LDCT screening among patients with smoking exposure. One large good-quality trial reported that screening was associated with significant reductions in lung cancer (20%) and all-cause (6.7%) mortality. Three small European trials showed no benefit of screening. Harms included radiation exposure, overdiagnosis, and a high rate of falsepositive findings that typically were resolved with further imaging. Smoking cessation was not affected. Incidental findings were common. Limitations: Three trials were underpowered and of insufficient duration to evaluate screening effectiveness. Overdiagnosis, an important harm of screening, is of uncertain magnitude. No studies reported results in women or minority populations. Conclusion: Strong evidence shows that LDCT screening can reduce lung cancer and all-cause mortality. The harms associated with screening must be balanced with the benefits. C1 Oregon Hlth & Sci Univ, Pacific Northwest Evidence Based Practice Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Humphrey, LL (reprint author), Oregon Hlth & Sci Univ, Mailcode BICC, Pacific Northwest Evidence Based Practice Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM linda.humphrey@va.gov OI Slatore, Christopher/0000-0003-0958-8122 FU AHRQ [HHSA-290-2007-10057-IEPC3]; Portland Veterans Affairs Medical Center; Veterans Affairs Health Services Research and Development Career Development Award FX By AHRQ under contract HHSA-290-2007-10057-IEPC3, task order 13, and the Portland Veterans Affairs Medical Center. Drs. Humphrey, Deffebach, and Slatore are supported by resources from the Portland Veterans Affairs Medical Center. Dr. Slatore is sponsored by a Veterans Affairs Health Services Research and Development Career Development Award. NR 100 TC 157 Z9 163 U1 2 U2 22 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 17 PY 2013 VL 159 IS 6 BP 411 EP + DI 10.7326/0003-4819-159-6-201309170-00690 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 234EY UT WOS:000325625900017 PM 23897166 ER PT J AU Lichterfeld, M Rosenberg, ES AF Lichterfeld, Mathias Rosenberg, Eric S. TI Acute HIV-1 Infection: A Call to Action SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY C1 [Lichterfeld, Mathias; Rosenberg, Eric S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray J-504,55 Fruit St, Boston, MA 02114 USA. EM erosenberg1@partners.org FU National Institutes of Health [AI098487, AI093203, AI071915] FX Dr. Lichterfeld is supported by grants AI098487 and AI093203 from the National Institutes of Health. Dr. Rosenberg is supported by grant AI071915 from the National Institutes of Health. NR 10 TC 1 Z9 1 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 17 PY 2013 VL 159 IS 6 BP 425 EP + DI 10.7326/0003-4819-159-6-201309170-00010 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 234EY UT WOS:000325625900020 PM 24042369 ER PT J AU Thompson, BT AF Thompson, B. Taylor TI Prone positioning for 16 h/d reduced mortality more than supine positioning in early severe ARDS SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; METAANALYSIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 17 PY 2013 VL 159 IS 6 AR JC2 DI 10.7326/0003-4819-159-6-201309170-02002 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 234EY UT WOS:000325625900001 PM 24042385 ER PT J AU Gerber, DE Dahlberg, SE Sandler, AB Ahn, DH Schiller, JH Brahmer, JR Johnson, DH AF Gerber, D. E. Dahlberg, S. E. Sandler, A. B. Ahn, D. H. Schiller, J. H. Brahmer, J. R. Johnson, D. H. TI Baseline tumour measurements predict survival in advanced non-small cell lung cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE non-small cell lung cancer; response evaluation criteria in solid tumours; survival; tumour size; tumour dimensions; baseline sum longest diameter ID RESPONSE EVALUATION CRITERIA; SOLID TUMORS; OVARIAN-CANCER; SIZE; CHEMOTHERAPY; CARCINOMA; THERAPY; VOLUME; PROGRESSION; PROGNOSIS AB Background: The association between tumour measurements and survival has been studied extensively in early-stage and locally advanced non-small cell lung cancer (NSCLC). We analysed these factors in patients with advanced NSCLC. Methods: Data were derived from the E4599 trial of paclitaxel-carboplatin +/- bevacizumab. Associations between the Response Evaluation Criteria in Solid Tumors (RECIST) baseline sum longest diameter (BSLD), response rate, progression-free survival (PFS) and overall survival (OS) were evaluated using univariate and multivariable Cox regression models. Results: A total of 759 of the 850 patients (89%) in the E4599 trial had measurable diseases and were included in this analysis. The median BSLD was 7.5 cm. BSLD predicted OS (hazard ratio (HR) 1.41; P<0.001) and had a trend towards association with PFS (HR 1.14; P=0.08). The median OS was 12.6 months for patients with BSLD<7.5 cm compared with 9.5 months for BSLD >= 7.5 cm. This association persisted in a multivariable model controlling multiple prognostic factors, including the presence and sites of extrathoracic disease (HR 1.24; P=0.01). There was no association between BSLD and response rate. Conclusion: Tumour measurements are associated with survival in the E4599 trial. If validated in other populations, this parameter may provide important prognostic information to patients and clinicians. C1 [Gerber, D. E.; Ahn, D. H.; Schiller, J. H.; Johnson, D. H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Dahlberg, S. E.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Sandler, A. B.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Brahmer, J. R.] Johns Hopkins Univ, Baltimore, MD 21231 USA. RP Gerber, DE (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM david.gerber@utsouthwestern.edu FU Public Health Service Grant from the National Cancer Institute, National Institutes of Health [CA23318]; Department of Health and Human Services; National Cancer Institute Cancer Clinical Investigator Team Leadership Award [1P30 CA142543-01]; North and Central Texas Clinical and Translational Science Initiative (NCTCTSI) [KL2RR024983] FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L Comis, MD) and supported in part by the Public Health Service Grant CA23318 from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. This work was also supported by a National Cancer Institute Cancer Clinical Investigator Team Leadership Award (1P30 CA142543-01 supplement) (to DEG) and the North and Central Texas Clinical and Translational Science Initiative (NCTCTSI) (KL2RR024983) (to DEG). The contents of this study are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 31 TC 3 Z9 5 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 17 PY 2013 VL 109 IS 6 BP 1476 EP 1481 DI 10.1038/bjc.2013.472 PG 6 WC Oncology SC Oncology GA 223NN UT WOS:000324812600013 PM 23942074 ER PT J AU Wu, D Pang, Y Wilkerson, MD Wang, D Hammerman, PS Liu, JS AF Wu, D. Pang, Y. Wilkerson, M. D. Wang, D. Hammerman, P. S. Liu, J. S. TI Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity SO BRITISH JOURNAL OF CANCER LA English DT Article DE squamous cell lung cancer subtypes; gene expression; RNAseq; microarray; signature genes; cells of origin; representative cell line; drug sensitivity; classification ID BIOCONDUCTOR; PROGNOSIS; CARCINOMA; SOFTWARE; TARGET; LINES AB Background: Squamous cell lung cancer (SqCC) is the second most common type of lung cancer in the United States. Previous studies have used gene-expression data to classify SqCC samples into four subtypes, including the primitive, classical, secretory and basal subtypes. These subtypes have different survival outcomes, although it is unknown whether these molecular subtypes predict response to therapy. Methods: Here, we analysed RNAseq data of 178 SqCC tumour samples and characterised the features of the different SqCC subtypes to define signature genes and pathway alterations specific to each subtype. Further, we compared the gene-expression features of each molecular subtype to specific time points in models of airway development. We also classified SqCC-derived cell lines and their reported therapeutic vulnerabilities. Results: We found that the primitive subtype may come from a later stage of differentiation, whereas the basal subtype may be from an early time. Most SqCC cell lines responded to one of five anticancer drugs (Panobinostat, 17-AAG, Irinotecan, Topotecan and Paclitaxel), whereas the basal-type cell line EBC-1 was sensitive to three other drugs (PF2341066, AZD6244 and PD-0325901). Conclusion: Compared with the other three subtypes of cell lines, the secretory-type cell lines were significantly less sensitive to the five most effective drugs, possibly because of their low proliferation activity. We provide a bioinformatics framework to explore drug repurposing for cancer subtypes based on the available genomic profiles of tumour samples, normal cell types, cancer cell lines and data of drug sensitivity in cell lines. C1 [Wu, D.; Liu, J. S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Wu, D.; Wang, D.] Monash Univ, Monash Inst Med Res, Ctr Canc Res, Clayton, Vic, Australia. [Pang, Y.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Wilkerson, M. D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Hammerman, P. S.] MIT, Eli & Edythe L Broad Inst Massachusetts, Cambridge, MA 02139 USA. [Hammerman, P. S.] Harvard Univ, Cambridge, MA 02138 USA. [Hammerman, P. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wu, D (reprint author), Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. EM dwu@fas.harvard.edu; jliu@stat.harvard.edu FU Australian National Health and Medical Research Council [1036541]; National Science Foundation [NSF IIS-1017967] FX We thank Drs Neil Hayes at the University of North Carolina at Chapel Hill for providing the SqCC subtype information of the samples in Raponi et al (2006), Alan Dabney at Department of Statistics, Texas A&M University for providing the R code of ClaNC, Heidi Greulich for helping to find the CCLE data sets, Ke Deng and Simeng Han at Harvard Statistics for their discussion, Catherine Wu for proof reading, Laurent Jacob and Terry Speed at the Statistics Department UC Berkely for their suggestion about classification methods, Gordon Smyth and Charity Law at the Walter and Eliza Hall Institute for providing suggestions on how to use 'voom', Robert Plenge at Brigham Women Hospital, Tianxi Cai at Harvard Biostatistics, Bryan Williams at Monash Institute of Medical Research and Matthew Meyerson at Dana Farber Cancer Institute for being supportive. This work was supported by grants from the Australian National Health and Medical Research Council (1036541 to Di Wu), and National Science Foundation (NSF IIS-1017967 for publication). NR 30 TC 9 Z9 10 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 17 PY 2013 VL 109 IS 6 BP 1599 EP 1608 DI 10.1038/bjc.2013.452 PG 10 WC Oncology SC Oncology GA 223NN UT WOS:000324812600030 PM 24002593 ER PT J AU Jackson, A Kloverpris, HN Boffito, M Handley, A Atkins, M Hayes, P Gilmour, J Riddel, L Chen, F Bailey-Tippets, M Walker, B Ackland, J Sullivan, M Goulder, P AF Jackson, Akil Kloverpris, Henrik N. Boffito, Marta Handley, Amanda Atkins, Mark Hayes, Peter Gilmour, Jill Riddel, Lynn Chen, Fabian Bailey-Tippets, Melanie Walker, Bruce Ackland, Jim Sullivan, Mark Goulder, Philip TI A Randomised, Placebo-Controlled, First-In-Human Study of a Novel Clade C Therapeutic Peptide Vaccine Administered Ex Vivo to Autologous White Blood Cells in HIV Infected Individuals SO PLOS ONE LA English DT Article ID VIRAL LOAD; IMMUNOTHERAPY; MACAQUES; RESPONSES; GAG AB Background: Preclinical studies of overlapping 15mer peptides, spanning SIV, SHIV or HIV, pulsed on autologous PBMC ex vivo have demonstrated high level, virus-specific T cell responses and viral suppression in non-human primates (NHP). Opal-HIV-Gag(c) consists of 120 synthetic 15mer peptides spanning Clade C, consensus Gag, manufactured to current good manufacturing practice; having been evaluated in a good laboratory practice toxicology study in Macaca mulatta. We evaluated the safety and preliminary immunogenicity of such peptides administered intravenously after short-duration ex vivo incubation, to HIV-positive adults on suppressive antiretroviral therapy. Methods and Findings: A first-in-human, placebo-controlled, double-blind, dose escalation study was conducted. Twenty-three patients with virus suppressed by antiretroviral therapy were enrolled in four groups 12 mg (n = 6), 24 mg (n = 6), 48 mg (n = 2) or matching placebo (n = 8). Treatment was administered intravenously after bedside enrichment of 120 mL whole blood for white cells using a closed system (Sepax S-100 device), with ex vivo peptide admixture (or diluent alone) and 37 degrees C incubation for one hour prior to reinfusion. Patients received 4 administrations at monthly intervals followed by a 12-week observation post-treatment. Opal-HIV-Gag(c) was reasonably tolerated at doses of 12 and 24 mg. There was an increased incidence of temporally associated pyrexia, chills, and transient/self-limiting lymphopenia in Opal-HIV-Gag(c) recipients compared to placebo. The study was terminated early, after two patients were recruited to the 48 mg cohort; a serious adverse event of hypotension, tachycardia secondary to diarrhoea occurred following a single product administration. An infectious cause for the event could not be identified, leaving the possibility of immunologically mediated product reaction. Conclusions: A serious, potentially life-threatening event of hypotension led to early, precautionary termination of the study. In the absence of a clearly defined mechanism or ability to predict such occurrence, further development of Opal-HIV-Gag(c) will not be undertaken in the current form. Registration: ClinicalTrials.gov NCT01123915; EudraCT: 2008-005142-23 C1 [Jackson, Akil; Boffito, Marta] St Stephens AIDS Trust, Chelsea & Westminster Hosp, London, England. [Kloverpris, Henrik N.; Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. [Handley, Amanda; Sullivan, Mark] Med Dev, Melbourne, Vic, Australia. [Atkins, Mark; Hayes, Peter; Gilmour, Jill] Univ London Imperial Coll Sci Technol & Med, London, England. [Riddel, Lynn] Northampton Gen Hosp, Dept Genitourinary Med, Northampton, England. [Chen, Fabian] Royal Berkshire Hosp, Dept Sexual Hlth, Reading RG1 5AN, Berks, England. [Bailey-Tippets, Melanie] INC, Oakleigh, Vic, Australia. [Walker, Bruce; Goulder, Philip] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Ackland, Jim] Global Biosolut, Craigieburn, Vic, Australia. [Kloverpris, Henrik N.] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. [Kloverpris, Henrik N.] Univ Kwazulu Natal, K RITH, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. RP Jackson, A (reprint author), St Stephens AIDS Trust, Chelsea & Westminster Hosp, London, England. EM akil.jackson@chelwest.nhs.uk FU Phillip T; Susan M Ragon Foundation FX The funding for this project was provided by the Phillip T and Susan M Ragon Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 0 Z9 0 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 17 PY 2013 VL 8 IS 9 AR e73765 DI 10.1371/journal.pone.0073765 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219YJ UT WOS:000324547300022 ER PT J AU Tierney, ESS Gal, D Gauvreau, K Baker, AL Trevey, S O'Neill, SR Jaff, MR de Ferranti, S Fulton, DR Colan, SD Newburger, JW AF Tierney, Elif Seda Selamet Gal, Dana Gauvreau, Kimberly Baker, Annette L. Trevey, Shari O'Neill, Stephen R. Jaff, Michael R. de Ferranti, Sarah Fulton, David R. Colan, Steven D. Newburger, Jane W. TI Vascular Health in Kawasaki Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atherosclerosis; coronary artery aneurysm; endothelial function; Kawasaki; vascular health ID INTIMA-MEDIA THICKNESS; CARDIOVASCULAR RISK-FACTORS; AMERICAN-HEART-ASSOCIATION; LONG-TERM MANAGEMENT; C-REACTIVE PROTEIN; ENDOTHELIAL FUNCTION; CORONARY-ARTERIES; INTRAVASCULAR ULTRASOUND; ESSENTIAL-HYPERTENSION; RHEUMATIC-FEVER AB Objectives The objective of our study was to compare the indices of vascular health in Kawasaki disease (KD) patients to those of control subjects. Background The literature on peripheral vascular health after KD is conflicting. Methods Subjects were patients 11 to 29 years of age with the onset of KD >12 months before the study visit (n = 203) and healthy control subjects (n = 50). We measured endothelial function (using the Endothelial Pulse Amplitude Testing index), intima-media thickness (IMT) of the right common carotid artery (RCCA) and the left common carotid artery (LCCA), and fasting lipid profile and C-reactive protein (CRP). KD patients were classified according to their worst-ever coronary artery (CA) status: group I, always normal CAs (n = 136, 67%); group II, CA z-scores >= 2 but <3 (n = 20, 10%); group III, CA aneurysm z-scores >= 3 but <8 mm (n = 40, 20%); and group IV, giant CA aneurysm, defined as >= 8 mm (n = 7, 3%). Results At a median of 11.6 years (range, 1.2 to 26 years) after KD onset, compared with controls, KD patients had a higher peak velocity in the LCCA (p = 0.04) and higher pulsatility index of both the RCCA and LCCA (p = 0.006 and p = 0.05, respectively). However, there were no differences in the Endo-PAT index or carotid IMT or stiffness. The mean IMT of the LCCA tended to differ across the KD subgroups and control group (p = 0.05), with a higher mean in group IV. Otherwise the KD subgroups and control group had similar vascular health indexes. Conclusions In contrast to some earlier reports, our study of North American children and young adults demonstrated that KD patients whose maximum CA dimensions were either always normal or mildly ectatic have normal vascular health indexes, providing reassurance regarding peripheral vascular health in this population. (C) 2013 by the American College of Cardiology Foundation C1 [Tierney, Elif Seda Selamet; Gal, Dana; Gauvreau, Kimberly; Baker, Annette L.; Trevey, Shari; O'Neill, Stephen R.; de Ferranti, Sarah; Fulton, David R.; Colan, Steven D.; Newburger, Jane W.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Tierney, Elif Seda Selamet; Gal, Dana; Gauvreau, Kimberly; Baker, Annette L.; Trevey, Shari; O'Neill, Stephen R.; de Ferranti, Sarah; Fulton, David R.; Colan, Steven D.; Newburger, Jane W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Tierney, Elif Seda Selamet] Stanford Univ, Dept Pediat, Div Pediat Cardiol, Stanford, CA 94305 USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA USA. RP Tierney, ESS (reprint author), Stanford Univ, Pediat Heart Ctr, 750 Welch Rd,Suite 350,Mail Code 5731, Palo Alto, CA 94304 USA. EM tierneys@stanford.edu FU American Heart Association, National Scientist Development Award; Farb and McCance Family Funds FX Supported by the American Heart Association, National Scientist Development Award, and the Farb and McCance Family Funds. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 50 TC 14 Z9 15 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 17 PY 2013 VL 62 IS 12 BP 1114 EP 1121 DI 10.1016/j.jacc.2013.04.090 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213HX UT WOS:000324047800014 ER PT J AU Samie, M Wang, X Zhang, XL Goschka, A Li, XR Cheng, XP Gregg, E Azar, M Zhuo, Y Garrity, AG Gao, Q Slaugenhaupt, S Pickel, J Zolov, SN Weisman, LS Lenk, GM Titus, S Bryant-Genevier, M Southall, N Juan, M Ferrer, M Xu, HX AF Samie, Mohammad Wang, Xiang Zhang, Xiaoli Goschka, Andrew Li, Xinran Cheng, Xiping Gregg, Evan Azar, Marlene Zhuo, Yue Garrity, Abigail G. Gao, Qiong Slaugenhaupt, Susan Pickel, Jim Zolov, Sergey N. Weisman, Lois S. Lenk, Guy M. Titus, Steve Bryant-Genevier, Marthe Southall, Noel Juan, Marugan Ferrer, Marc Xu, Haoxing TI A TRP Channel in the Lysosome Regulates Large Particle Phagocytosis via Focal Exocytosis SO DEVELOPMENTAL CELL LA English DT Article ID MUCOLIPIDOSIS TYPE-IV; INTRACELLULAR CA2+ STORES; PLASMA-MEMBRANE REPAIR; PHAGOSOME MATURATION; HUMAN NEUTROPHILS; MACROPHAGES; CALCIUM; SECRETION; DYNAMICS; TRAFFICKING AB Phagocytosis of large extracellular particles such as apoptotic bodies requires delivery of the intracellular endosomal and lysosomal membranes to form plasmalemmal pseudopods. Here, we identified mucolipin TRP channel 1 (TRPML1) as the key lysosomal Ca2+ channel regulating focal exocytosis and phagosome biogenesis. Both particle ingestion and lysosomal exocytosis are inhibited by synthetic TRPML1 blockers and are defective in macrophages isolated from TRPML1 knockout mice. Furthermore, TRPML1 overexpression and TRPML1 agonists facilitate both lysosomal exocytosis and particle uptake. Using time-lapse confocal imaging and direct patch clamping of phagosomal membranes, we found that particle binding induces lysosomal PI(3,5)P-2 elevation to trigger TRPML1-mediated lysosomal Ca2+ release specifically at the site of uptake, rapidly delivering TRPML1-resident lysosomal membranes to nascent phagosomes via lysosomal exocytosis. Thus phagocytic ingestion of large particles activates a phosphoinositide- and Ca2+-dependent exocytosis pathway to provide membranes necessary for pseudopod extension, leading to clearance of senescent and apoptotic cells in vivo. C1 [Samie, Mohammad; Wang, Xiang; Zhang, Xiaoli; Goschka, Andrew; Li, Xinran; Cheng, Xiping; Gregg, Evan; Azar, Marlene; Zhuo, Yue; Garrity, Abigail G.; Gao, Qiong; Xu, Haoxing] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. [Lenk, Guy M.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Zolov, Sergey N.; Weisman, Lois S.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Zolov, Sergey N.; Weisman, Lois S.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Slaugenhaupt, Susan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Genet,Ctr Human Genet Res, Boston, MA 02114 USA. [Pickel, Jim] NIH, NIMH Transgen, Bethesda, MD 20892 USA. [Titus, Steve; Bryant-Genevier, Marthe; Southall, Noel; Juan, Marugan; Ferrer, Marc] NIH, NCATS, NCGC, Rockville, MD 20850 USA. RP Xu, HX (reprint author), Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. EM haoxingx@umich.edu RI Southall, Noel/H-8991-2012; Lenk, Guy/Q-1226-2016 OI Southall, Noel/0000-0003-4500-880X; Lenk, Guy/0000-0001-8092-1405 FU National Institutes of Health (NIH) [NS062792, MH096595, AR060837, GM24872, NS064015] FX This work was supported by National Institutes of Health (NIH) (NS062792, MH096595, AR060837 to H.X, GM24872 to M. Meisler, and NS064015 to L.S.W). We are grateful to Dr. Loren Looger for the GCaMP3 construct, Drs. Norma Andrews and Thomas Sudhof for the Syt-VII construct, Florence Niedergang and Robert Edwards for VAMP7 constructs, Ed Stuenkel for the TeNT construct, Johnny Fares for ML1-overexpressing or knockdown RAW macrophages, Gregg Sobocinski for assistance in confocal imaging, and Richard Hume and Miriam Meisler for comments on an earlier version of the manuscript. We appreciate the encouragement and helpful comments from other members of the Xu laboratory. NR 53 TC 58 Z9 58 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD SEP 16 PY 2013 VL 26 IS 5 BP 511 EP 524 DI 10.1016/j.devcel.2013.08.003 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 243GF UT WOS:000326304200006 PM 23993788 ER PT J AU Mann, JK Byakwaga, H Kuang, XMT Le, AQ Brumme, CJ Mwimanzi, P Omarjee, S Martin, E Lee, GQ Baraki, B Danroth, R McCloskey, R Muzoora, C Bangsberg, DR Hunt, PW Goulder, PJR Walker, BD Harrigan, PR Martin, JN Ndung'u, T Brockman, MA Brumme, ZL AF Mann, Jaclyn K. Byakwaga, Helen Kuang, Xiaomei T. Le, Anh Q. Brumme, Chanson J. Mwimanzi, Philip Omarjee, Saleha Martin, Eric Lee, Guinevere Q. Baraki, Bemuluyigza Danroth, Ryan McCloskey, Rosemary Muzoora, Conrad Bangsberg, David R. Hunt, Peter W. Goulder, Philip J. R. Walker, Bruce D. Harrigan, P. Richard Martin, Jeff N. Ndung'u, Thumbi Brockman, Mark A. Brumme, Zabrina L. TI Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes SO RETROVIROLOGY LA English DT Article DE HIV/AIDS; Nef; Viral diversity; Pathogenesis; CD4; HLA class I ID IMMUNODEFICIENCY-VIRUS TYPE-1; COMPLEX CLASS-I; HUMAN-LEUKOCYTE ANTIGEN; DISEASE PROGRESSION; ANTIRETROVIRAL THERAPY; GENETIC-CHARACTERIZATION; ELITE CONTROLLERS; INFECTION; REPLICATION; PROTEINS AB Background: The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison of Nef in vitro function has not been undertaken. Here, we investigate two of Nef's most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. Results: Single HIV-1 plasma RNA Nef clones were obtained from N= 360 antiretroviral-na ve, chronically infected patients from Africa and North America: 96 (subtype A), 93 (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed by flow cytometry. Nef expression was verified by Western blot. Subset analyses and multivariable linear regression were used to adjust for differences in age, sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef sequences were synthesized and functionally assessed. Exploratory sequence analyses were performed to identify potential genotypic correlates of Nef function. Subtype B Nef clones displayed marginally greater CD4 downregulation activity (p = 0.03) and markedly greater HLA class I downregulation activity (p < 0.0001) than clones from other subtypes. Subtype C Nefs displayed the lowest in vitro functionality. Inter-subtype differences in HLA class I downregulation remained statistically significant after controlling for differences in age, sex, and clinical parameters (p < 0.0001). The synthesized consensus subtype B Nef showed higher activities compared to consensus C Nef, which was most pronounced in cells expressing lower protein levels. Nef clones exhibited substantial inter-subtype diversity: cohort consensus residues differed at 25% of codons, while a similar proportion of codons exhibited substantial inter-subtype differences in major variant frequency. These amino acids, along with others identified in intra-subtype analyses, represent candidates for mediating inter-subtype differences in Nef function. Conclusions: Results support a functional hierarchy of subtype B > A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms underlying these differences and their relevance to HIV-1 pathogenicity merit further investigation. C1 [Mann, Jaclyn K.; Omarjee, Saleha; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Durban, South Africa. [Mann, Jaclyn K.; Omarjee, Saleha; Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Byakwaga, Helen; Muzoora, Conrad] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Byakwaga, Helen; Hunt, Peter W.; Martin, Jeff N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kuang, Xiaomei T.; Mwimanzi, Philip; Martin, Eric; Baraki, Bemuluyigza; Danroth, Ryan; Brockman, Mark A.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. [Le, Anh Q.; Mwimanzi, Philip; Baraki, Bemuluyigza; Danroth, Ryan; McCloskey, Rosemary; Brockman, Mark A.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Brumme, Chanson J.; Martin, Eric; Lee, Guinevere Q.; McCloskey, Rosemary; Harrigan, P. Richard; Brockman, Mark A.; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Bangsberg, David R.; Walker, Bruce D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bangsberg, David R.; Walker, Bruce D.] Harvard Univ, Boston, MA 02115 USA. [Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. [Walker, Bruce D.; Ndung'u, Thumbi] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Walker, Bruce D.; Ndung'u, Thumbi] Harvard Univ, Cambridge, MA 02138 USA. [Walker, Bruce D.] Howard Hughes Med Res Inst, Chevy Chase, MD USA. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, D-10117 Berlin, Germany. RP Brockman, MA (reprint author), Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. EM mark_brockman@sfu.ca; zbrumme@sfu.ca RI Lee, Guinevere/D-4436-2017; OI Lee, Guinevere/0000-0002-9412-886X; Ndung'u, Thumbi/0000-0003-2962-3992; Brumme, Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426 FU operating grants from the Canadian Institutes for Health Research (CIHR); Canada-Sub Saharan Africa (CANSSA); Global Health Research Initiative (GHRI); Canadian International Development Agency (CIDA); International Development Research Centre (IDRC); Canada Graduate Scholarship from CIHR; Master's Scholarship from the Canadian Association for HIV Research and Abbott Virology; Merck-Canada Training of Aboriginal Youth in Biomedical Labs program; Research-Undergraduate Student Research Award; Victor Daitz Chair in HIV/TB Research and an International Early Career Scientist Award from the Howard Hughes Medical Institute; Michael Smith Foundation for Health Research; [MOP-93536]; [HOP-115700] FX We thank Dr. Art FY Poon for assistance with HIV-1 sequence alignments. This work was supported by operating grants from the Canadian Institutes for Health Research (CIHR) (MOP-93536 and HOP-115700, to ZLB and MAB). JKM and HB received a pilot grant from the Canada-Sub Saharan Africa (CANSSA) HIV/AIDS Network through funding provided by the Global Health Research Initiative (GHRI), itself a collaborative research funding partnership of the CIHR, the Canadian International Development Agency (CIDA), and the International Development Research Centre (IDRC). CJB is supported by a Vanier Canada Graduate Scholarship from CIHR. EM was supported by a Master's Scholarship from the Canadian Association for HIV Research and Abbott Virology. RD is supported by the Merck-Canada Training of Aboriginal Youth in Biomedical Labs program, while RMM received a Vice President Research-Undergraduate Student Research Award, both at Simon Fraser University. TN holds the South African DST/NRF Research Chair in Systems Biology of HIV/AIDS, the Victor Daitz Chair in HIV/TB Research and an International Early Career Scientist Award from the Howard Hughes Medical Institute. MAB holds a Canada Research Chair in Viral Pathogenesis and Immunity. ZLB is the recipient of a CIHR New Investigator Award and a Scholar Award from the Michael Smith Foundation for Health Research. The funders played no role in the study design; collection, analysis, or interpretation of data; or writing of this manuscript. NR 64 TC 21 Z9 22 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD SEP 16 PY 2013 VL 10 AR 100 DI 10.1186/1742-4690-10-100 PG 16 WC Virology SC Virology GA 228CZ UT WOS:000325164100003 PM 24041011 ER PT J AU Hanna, MC Go, C Roden, C Jones, RT Pochanard, P Javed, AY Javed, A Mondal, C Palescandolo, E Van Hummelen, P Hatton, C Bass, AJ Chun, SM Na, DC Kim, TI Jang, SJ Osarogiagbon, RU Hahn, WC Meyerson, M Garraway, LA MacConaill, LE AF Hanna, Megan C. Go, Christina Roden, Christine Jones, Robert T. Pochanard, Panisa Javed, Ahmed Yasir Javed, Awais Mondal, Chandrani Palescandolo, Emanuele Van Hummelen, Paul Hatton, Charles Bass, Adam J. Chun, Sung Min Na, Deuk Chae Kim, Tae-Im Jang, Se Jin Osarogiagbon, Raymond U. Hahn, William C. Meyerson, Matthew Garraway, Levi A. MacConaill, Laura E. TI Colorectal Cancers from Distinct Ancestral Populations Show Variations in BRAF Mutation Frequency SO PLOS ONE LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; LUNG-CANCER; MOLECULAR ANALYSIS; KOREA INCIDENCE; KRAS MUTATIONS; GENE-MUTATIONS; RAS MUTATIONS; COLON-CANCER; HUMAN-BREAST; SURVIVAL AB It has been demonstrated for some cancers that the frequency of somatic oncogenic mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF mutations occurred at a higher frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer. C1 [Hanna, Megan C.; Go, Christina; Roden, Christine; Jones, Robert T.; Pochanard, Panisa; Mondal, Chandrani; Palescandolo, Emanuele; Van Hummelen, Paul; Hatton, Charles; Hahn, William C.; Meyerson, Matthew; Garraway, Levi A.; MacConaill, Laura E.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Hanna, Megan C.; Go, Christina; Roden, Christine; Jones, Robert T.; Pochanard, Panisa; Mondal, Chandrani; Palescandolo, Emanuele; Van Hummelen, Paul; Hatton, Charles; Bass, Adam J.; Hahn, William C.; Meyerson, Matthew; Garraway, Levi A.; MacConaill, Laura E.] Harvard Univ, Sch Med, Boston, MA USA. [Hanna, Megan C.; Go, Christina; Roden, Christine; Jones, Robert T.; Pochanard, Panisa; Mondal, Chandrani; Palescandolo, Emanuele; Van Hummelen, Paul; Hatton, Charles; Bass, Adam J.; Hahn, William C.; Meyerson, Matthew; Garraway, Levi A.; MacConaill, Laura E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hanna, Megan C.; Bass, Adam J.; Hahn, William C.; Meyerson, Matthew; Garraway, Levi A.; MacConaill, Laura E.] Broad Inst, Cambridge, MA USA. [Javed, Ahmed Yasir; Javed, Awais; Osarogiagbon, Raymond U.] Boston Baskin Canc Fdn, Baptist Canc Ctr, Memphis, TN USA. [Chun, Sung Min; Na, Deuk Chae; Kim, Tae-Im; Jang, Se Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea. RP MacConaill, LE (reprint author), Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. EM Laura_Macconaill@dfci.harvard.edu FU Dana-Farber Cancer Institute; DF/HCC Pilot Program; Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF); Korean Ministry of Education, Science and Technology (MEST) [2011-0030105] FX This study was supported by the Dana-Farber Cancer Institute, the DF/HCC Pilot Program, and the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education, Science and Technology (MEST) (2011-0030105). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 13 Z9 13 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 16 PY 2013 VL 8 IS 9 AR UNSP e74950 DI 10.1371/journal.pone.0074950 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219GJ UT WOS:000324494000142 PM 24066160 ER PT J AU Vengust, M Staempfli, H Viel, L Swenson, ER Heigenhauser, G AF Vengust, Modest Staempfli, Henry Viel, Laurent Swenson, Erik R. Heigenhauser, George TI Acetazolamide attenuates transvascular fluid flux in equine lungs during intense exercise SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CARBONIC-ANHYDRASE INHIBITION; PULMONARY VASCULAR-RESISTANCE; HUMAN ERYTHROCYTE-MEMBRANE; RED-CELL MEMBRANE; ACID-BASE CONTROL; MAXIMAL EXERCISE; HEAVY EXERCISE; GAS-EXCHANGE; WATER PERMEABILITY; CAPILLARY-PRESSURE AB During intense exercise in horses the transvascular fluid flux in the pulmonary circulation (J(v-a)) represents 4% of cardiac output . This fluid flux has been attributed to an increase in pulmonary transmural hydrostatic forces, increases in perfused microvascular surface area, and reversible alterations in capillary permeability under conditions of high flow and pressure. Erythrocyte fluid efflux, however, accounts for a significant fraction of J(v-a). In the lung the Jacobs-Stewart cycle occurs with diffusion of CO2 into alveolar space with possible accompanying chloride (Cl-) and water movement from the erythrocyte directly into the pulmonary interstitium. We hypothesised that inhibition of carbonic anhydrase in erythrocytes inhibits the Jacobs-Stewart cycle and attenuates J(v-a). Five horses were exercised on a treadmill until fatigue without (control) and with acetazolamide treatment (30 mg kg(-1) 30 min before exercise). Erythrocyte fluid efflux, plasma fluid flux across the lung and J(v-a) were calculated using haemoglobin, haematocrit, plasma protein and Q. Fluid fluxes were used to calculate erythrocyte, plasma and whole blood Cl- fluxes across the lung. Cardiac output was not different between control and acetazolamide treatment. During exercise erythrocyte fluid efflux and J(v-a) increased in control (9.3 +/- 3.3 and 11.0 +/- 4.4 l min(-1), respectively) and was higher than after acetazolamide treatment (3.8 +/- 1.6 and 1.2 +/- 1.2 l min(-1), respectively) (P < 0.05). Plasma fluid flux did not change from rest in control and decreased after acetazolamide treatment (-4.5 +/- 1.5 l min(-1)) (P < 0.05). Erythrocyte Cl- flux increased during exercise in control and after acetazolamide treatment (P < 0.05). During exercise plasma Cl- flux across the lung did not change in control; however, it increased with acetazolamide treatment (P= 0.0001). During exercise whole blood Cl- flux increased across the lung in control (P < 0.05) but not after acetazolamide treatment. The results indicate that J(v-a) in the lung is dependent on the Jacobs-Stewart cycle and mostly independent of transmural hydrostatic forces. It also appears that J(v-a) is mediated by Cl- and water egress from erythrocytes directly into the interstitium without transit through plasma. C1 [Vengust, Modest] Univ Ljubljana, Fac Vet, SI-1115 Ljubljana, Slovenia. [Vengust, Modest; Viel, Laurent] Univ Guelph, Firestone Equine Resp Res Lab, Guelph, ON N1G 2W1, Canada. [Staempfli, Henry; Viel, Laurent] Univ Guelph, Dept Clin Studies, Guelph, ON N1G 2W1, Canada. [Swenson, Erik R.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Heigenhauser, George] McMaster Univ, Dept Med, Med Ctr, Hamilton, ON L8N 3Z5, Canada. RP Vengust, M (reprint author), Univ Ljubljana, Fac Vet, POB 3425, SI-1115 Ljubljana, Slovenia. EM modest.vengust@vf.uni-lj.si FU Ontario Ministry of Agriculture and Food - Equine Program; Department of Clinical Studies at the University of Guelph; Canadian Institutes of Health Research; Slovenian Research Agency [P4-0053] FX This study was supported by the Ontario Ministry of Agriculture and Food - Equine Program, Department of Clinical Studies at the University of Guelph, Canadian Institutes of Health Research and the Slovenian Research Agency grant P4-0053. NR 62 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 15 PY 2013 VL 591 IS 18 BP 4499 EP 4513 DI 10.1113/jphysiol.2013.257956 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 219AU UT WOS:000324476900020 PM 23818694 ER PT J AU Goldberg, MS AF Goldberg, Michael S. TI siRNA Delivery for the treatment of ovarian cancer SO METHODS LA English DT Review DE siRNA; Targeted; Delivery; Ovarian cancer ID SYSTEMICALLY ADMINISTERED SIRNA; INTERFERING RNA DELIVERY; LIPID-LIKE MATERIALS; IN-VIVO DELIVERY; NONHUMAN-PRIMATES; TUMOR VASCULATURE; GENE; NANOPARTICLES; MICE; CELLS AB Short interfering RNAs (siRNAs) mediate the catalytic sequence-specific cleavage of target messenger RNA (mRNA) molecules, resulting in the silencing of gene products in an efficient and precise manner. One apparent application of this technology is the knockdown of genes responsible for cancer progression, including pro-proliferative oncogenes, inhibitors of apoptosis, and mediators of angiogenesis. Delivery of siRNAs into particular cells has remained the principal obstacle to the realization of the potential of RNA interference (RNAi) in the clinic. Several groups have worked to develop carriers that facilitate siRNA delivery into ovarian cancer cells in mouse models of ovarian cancer. The results have been promising, often leading to significant survival extension. Such benefit is critical for a disease that is characterized by very poor outcomes and demands novel treatment options. This review describes advancements in siRNA delivery for the treatment of ovarian cancer. (C) 2013 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Goldberg, MS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM michael_goldberg1@dfci.harvard.edu FU Ovarian Cancer Research Fund; Caring Together, NY Ovarian Cancer Research Grant FX I would like to thank the Ovarian Cancer Research Fund and the Caring Together, NY Ovarian Cancer Research Grant for their support of our research. NR 55 TC 4 Z9 5 U1 3 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD SEP 15 PY 2013 VL 63 IS 2 BP 95 EP 100 DI 10.1016/j.ymeth.2013.01.007 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 239EO UT WOS:000326005600002 PM 23403216 ER PT J AU Schoneburg, B Mancini, M Horak, F Nutt, JG AF Schoneburg, Bernadette Mancini, Martina Horak, Fay Nutt, John G. TI Framework for Understanding Balance Dysfunction in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Review DE balance; gait; posture; Parkinson's disease ID DEEP BRAIN-STIMULATION; ANTICIPATORY POSTURAL ADJUSTMENTS; SUBTHALAMIC NUCLEUS; STEP INITIATION; DUAL TASKING; GAIT VARIABILITY; STOOPED POSTURE; OLDER-ADULTS; SWAY; LEVODOPA AB People with Parkinson's disease (PD) suffer from progressive impairment in their mobility. Locomotor and balance dysfunction that impairs mobility in PD is an important cause of physical and psychosocial disability. The recognition and evaluation of balance dysfunction by the clinician are an essential component of managing PD. In this review, we describe a framework for understanding balance dysfunction in PD to help clinicians recognize patients who are at risk for falling and impaired mobility. (c) 2013 International Parkinson and Movement Disorder Society C1 [Schoneburg, Bernadette; Mancini, Martina; Horak, Fay; Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Schoneburg, Bernadette; Nutt, John G.] Portland VA Med Ctr, Portland, OR USA. RP Nutt, JG (reprint author), Parkinson Ctr Oregon, 3181 SW Sam Jackson Pk Rd W OP32, Portland, OR 97239 USA. EM nuttj@ohsu.edu FU PADRECC fellowship; National Institute of Aging; National Parkinson Foundation; National Institute of Neurological Disorders and Stroke; Ceregene FX This study has support from a PADRECC fellowship, the National Institute of Aging, the National Parkinson Foundation, the National Institute of Neurological Disorders and Stroke, and Ceregene. NR 96 TC 34 Z9 34 U1 6 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2013 VL 28 IS 11 SI SI BP 1474 EP 1482 DI 10.1002/mds.25613 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 238VI UT WOS:000325979100002 PM 23925954 ER PT J AU Luo, JH Rossouw, J Tong, E Giovino, GA Lee, CC Chen, C Ockene, JK Qi, LH Margolis, KL AF Luo, Juhua Rossouw, Jacques Tong, Elisa Giovino, Gary A. Lee, Cathy C. Chen, Chu Ockene, Judith K. Qi, Lihong Margolis, Karen L. TI Smoking and Diabetes: Does the Increased Risk Ever Go Away? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE risk factors; smoking; smoking cessation; type 2 diabetes ID BASE-LINE CHARACTERISTICS; MIDDLE-AGED MEN; CIGARETTE-SMOKING; UNITED-STATES; WEIGHT-GAIN; INSULIN-RESISTANCE; CESSATION; MELLITUS; PARTICIPANTS; HAZARDS AB Recent studies reported that smoking cessation leads to higher short-term risk of type 2 diabetes than continuing to smoke. However, the duration of increased diabetes risk following smoking cessation needs further investigation. We followed 135,906 postmenopausal women aged 50-79 years enrolled in the Women's Health Initiative between September 1, 1993, and December 31, 1998, over an average of 11 years to examine the association between smoking cessation and risk of diabetes using Cox proportional hazard multivariable-adjusted regression models. Compared with that for never smokers, the risk for diabetes was significantly elevated in current smokers (hazard ratio = 1.28, 95% confidence interval: 1.20, 1.36) but was even higher in women who quit smoking during the first 3 years of follow-up (hazard ratio = 1.43, 95% confidence interval: 1.26, 1.63). Among former smokers, the risk of diabetes decreased significantly as the time since quitting increased and was equal to that of never smokers following a cessation period of 10 years. In new quitters with low cumulative exposure (<20 pack-years), diabetes risk was not elevated following smoking cessation. In conclusion, the risk of diabetes in former smokers returns to that in never smokers 10 years after quitting, and even more quickly in lighter smokers. C1 [Luo, Juhua] W Virginia Univ, Dept Community Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Rossouw, Jacques] NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Tong, Elisa] Univ Calif Davis, Med Ctr, Div Gen Internal Med, Sacramento, CA 95817 USA. [Giovino, Gary A.] SUNY Buffalo, Dept Community Hlth & Hlth Behav, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. [Lee, Cathy C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Div Geriatr, Los Angeles, CA 90095 USA. [Lee, Cathy C.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. [Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Ockene, Judith K.] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA USA. [Qi, Lihong] Univ Calif Davis, Div Biostat, Dept Publ Hlth Sci, Sch Med, Davis, CA 95616 USA. [Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA. RP Luo, JH (reprint author), Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 1025 East 7th St, Bloomington, IN 47405 USA. EM juhluo@indiana.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, 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]; [HHSN268201100003C] FX The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, 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, and by HHSN268201100003C. NR 41 TC 11 Z9 11 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 2013 VL 178 IS 6 BP 937 EP 945 DI 10.1093/aje/kwt071 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 227YC UT WOS:000325150600016 PM 23817918 ER PT J AU Lebron-Milad, K Tsareva, A Ahmed, N Milad, MR AF Lebron-Milad, K. Tsareva, A. Ahmed, N. Milad, M. R. TI Sex differences and estrous cycle in female rats interact with the effects of fluoxetine treatment on fear extinction SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Fear; Estrous cycle; Estrogen; Fluoxetine; Gonadal hormones; Anxiety disorders ID SEROTONIN REUPTAKE INHIBITORS; POSTTRAUMATIC-STRESS-DISORDER; 5-HT2C RECEPTOR ANTAGONIST; CITALOPRAM INCREASES FEAR; MEDIAL PREFRONTAL CORTEX; CONDITIONED FEAR; ANXIETY DISORDERS; MESSENGER-RNA; AMYGDALA; WOMEN AB A common treatment for anxiety disorders is chronic administration of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Recent data suggest that SSRIs modulate fear responses after conditioned fear extinction and that gonadal hormones influence fear extinction. In this study we investigated the influence of sex and the estrous cycle on the effects of acute (experiment 1) and chronic (experiment 2) fluoxetine treatment on fear extinction. In experiment 1, rats received tone-footshock pairings during day 1. On day 2, rats received either fluoxetine (10 mg/kg in 0.5 mL) or vehicle prior to extinction learning. On day 3, extinction memory was assessed during extinction recall. In experiment 2, rats were exposed to a similar behavioral protocol, except that fluoxetine and vehicle were administered for 14 consecutives days after conditioning (days 2-15). Extinction learning and extinction recall occurred on days 15 and 16, respectively. Acute administration of fluoxetine increased fear responses equally in males and females during extinction learning and extinction recall. Chronic administration of fluoxetine reduced fear responses during extinction learning and extinction recall in female but not in male rats and this effect seems to be modulated by the estrous cycle. The SSRI-induced reduction of freezing during extinction learning and recall suggest a general anxiolytic effect of the drug treatment rather than a specific effect on extinction learning per se. Our data show evidence of sex-specific anxiolytic effects of 14-day treatment of fluoxetine while the acute anxiogenic effect of SSRI seems independent of sex effects. (C) 2013 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lebron-Milad, K (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 149 13th St,CNY 2602, Charlestown, MA 02129 USA. EM kmilad@nmr.mgh.harvard.edu FU National Institute of Mental Health [1R01MH097880-001]; Department of Psychiatry at Massachusetts General Hospital FX This work was supported by the National Institute of Mental Health Grant 1R01MH097880-001 and institutional funds from the Department of Psychiatry at Massachusetts General Hospital to MRM. The authors also appreciate Kara Cover, Edward Pace-Schott, Marie-France Mann and Aaron Landau for reviewing the manuscript. NR 50 TC 18 Z9 19 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP 15 PY 2013 VL 253 BP 217 EP 222 DI 10.1016/j.bbr.2013.07.024 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 222GZ UT WOS:000324720500029 PM 23886596 ER PT J AU Choueiri, TK Fay, AP Gagnon, R Lin, Y Bahamon, B Brown, V Rosenberg, JE Hutson, TE Baker-Neblett, KL Carpenter, C Liu, Y Pandite, L Signoretti, S AF Choueiri, Toni K. Fay, Andre P. Gagnon, Robert Lin, Ying Bahamon, Brittany Brown, Victoria Rosenberg, Jonathan E. Hutson, Thomas E. Baker-Neblett, Katherine L. Carpenter, Christopher Liu, Yuan Pandite, Lini Signoretti, Sabina TI The Role of Aberrant VHL/HIF Pathway Elements in Predicting Clinical Outcome to Pazopanib Therapy in Patients with Metastatic Clear-Cell Renal Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID KIDNEY CANCER; SUPPRESSOR GENE; EXPRESSION; TISSUE; IDENTIFICATION; SUBTYPES; 1-ALPHA AB Purpose: Inactivation of von Hippel-Lindau (VHL) gene in clear-cell renal cell carcinoma (RCC) leads to increased levels of hypoxia-inducible factors (HIF) and overexpression of HIF target genes, such as VEGF and others. VEGF-targeted agents are standard in advanced clear-cell RCC but biomarkers of activity are lacking. Experimental Design: We analyzed tumor tissue samples from metastatic clear-cell RCC patients who received pazopanib as part of clinical trial VEG102616. We evaluated several components of the VHL/HIF pathway: VHL gene inactivation (mutation and/or methylation), HIF-1 alpha and HIF-2 alpha immunohistochemistry staining, and HIF-1 alpha transcriptional signature. We evaluated the association of these biomarkers with best overall response rate (ORR) and progression-free survival (PFS) to pazopanib, a standard first-line VEGF-targeted agent. Results: The VEG102616 trial enrolled 225 patients, from whom 78 samples were available for tumor DNA extraction. Of these, 70 patients had VHL mutation or methylation. VHL gene status did not correlate with ORR or PFS. Similarly, HIF-1 alpha (65 samples) and HIF-2 alpha (66 samples) protein levels (high vs. low) did not correlate with ORR or PFS to pazopanib. The HIF-1 alpha transcriptional signature (46 samples) was enriched in tumors expressing high HIF-1 alpha levels. However, the HIF-1 alpha gene expression signature was not associated with clinical outcome to pazopanib. Conclusions: In patients with advanced clear-cell RCC, several potential biomarkers along the VHL/HIF-1 alpha/HIF-2 alpha axis were not found to be predictive for pazopanib activity. Additional efforts must continue to identify biomarkers associated with clinical outcome to VEGF-targeted agents in metastatic RCC. (C) 2013 AACR. C1 [Choueiri, Toni K.; Fay, Andre P.; Signoretti, Sabina] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.; Bahamon, Brittany; Brown, Victoria; Signoretti, Sabina] Brigham & Womens Hosp, Boston, MA 02115 USA. [Choueiri, Toni K.; Signoretti, Sabina] Harvard Univ, Sch Med, Boston, MA USA. [Gagnon, Robert; Lin, Ying; Baker-Neblett, Katherine L.; Carpenter, Christopher; Liu, Yuan; Pandite, Lini] GlaxoSmithKline, Collegeville, PA USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hutson, Thomas E.] Texas Oncol Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. RP Signoretti, S (reprint author), Brigham & Womens Hosp, 75 Francis St Thorn Bld,504A, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu; ssignoretti@partners.org OI Rosenberg, Jonathan/0000-0003-2637-4249 FU GlaxoSmithKline Pharmaceuticals, Philadelphia, Pennsylvania; Dana-Farber/Harvard Cancer Center Kidney Cancer Program FX This work was supported in part by GlaxoSmithKline Pharmaceuticals, Philadelphia, Pennsylvania, and the Dana-Farber/Harvard Cancer Center Kidney Cancer Program. NR 35 TC 30 Z9 31 U1 0 U2 6 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 SEP 15 PY 2013 VL 19 IS 18 BP 5218 EP 5226 DI 10.1158/1078-0432.CCR-13-0491 PG 9 WC Oncology SC Oncology GA 219NF UT WOS:000324513000032 PM 23881929 ER PT J AU Gagne, V Rousseau, J Labuda, M Sharif-Askari, B Brukner, I Laverdiere, C Ceppi, F Sallan, SE Silverman, LB Neuberg, D Kutok, JL Sinnett, D Krajinovic, M AF Gagne, Vincent Rousseau, Julie Labuda, Malgorzata Sharif-Askari, Bahram Brukner, Ivan Laverdiere, Caroline Ceppi, Francesco Sallan, Stephen E. Silverman, Lewis B. Neuberg, Donna Kutok, Jeffery L. Sinnett, Daniel Krajinovic, Maja TI Bim Polymorphisms: Influence on Function and Response to Treatment in Children with Acute Lymphoblastic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID GLUCOCORTICOID-INDUCED APOPTOSIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; BCL-2 RELATIVE BIM; CELL-DEATH; BH3-ONLY PROTEINS; LYMPHOID-CELLS; RESISTANCE; CHILDHOOD; GENE; MECHANISMS AB Purpose: Corticosteroids induce apoptosis in the malignant lymphoid cells and are critical component of combination therapy for acute lymphoblastic leukemia (ALL). Several genome-wide microarray studies showed major implication of proapoptotic Bim in mediating corticosteroid-related resistance in leukemia cells. Experimental Design: We investigated Bim gene polymorphisms and their association with childhood ALL outcome, and the mechanism underlying the observed finding. Results: Lower overall survival (OS) was associated with Bim C29201T located in Bcl-2 homology 3 (BH3) domain (P = 0.01). An association remained significant in multivariate model (P = 0.007), was more apparent in high-risk patients (P = 0.004) and patients treated with dexamethasone (P = 0.009), and was subsequently confirmed in the replication patient cohort (P = 0.03). RNA analysis revealed that C29201T affects generation of gamma isoforms (gamma 1) that lack proapoptotic BH3 domain. The phenotypic effect was minor suggesting the influence of additional factors that may act in conjunction with Bim genotype. Combined analysis with Mcl gene polymorphism (G-486T) revealed profound reduction in OS in individuals with both risk genotypes (P < 0.0005 in discovery and P = 0.002 in replication cohort) and particularly in high-risk patients (P <= 0.008). Conclusions: Increased expression of prosurvival Mcl1 and presence of Bim isoforms lacking proapoptotic function might explain marked reduction of OS in a disease and dose-dependent manner in ALL patients carrying Bim- and Mcl1-risk genotypes. (C) 2013 AACR. C1 [Gagne, Vincent; Rousseau, Julie; Labuda, Malgorzata; Sharif-Askari, Bahram; Laverdiere, Caroline; Ceppi, Francesco; Sinnett, Daniel; Krajinovic, Maja] CHU St Justine, Ctr Rech, Charles Bruneau Canc Ctr, Montreal, PQ H3T 1C5, Canada. [Laverdiere, Caroline; Sinnett, Daniel; Krajinovic, Maja] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Krajinovic, Maja] Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada. [Brukner, Ivan] McGill Univ, Jewish Gen Hosp, Dept Diagnost Med, Montreal, PQ H3T 1E2, Canada. [Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Krajinovic, M (reprint author), CHU St Justine, Ctr Rech, 3175 Chemin Cote Ste Catherine, Montreal, PQ H3T 1C5, Canada. EM maja.krajinovic@umontreal.ca FU Canadian Institutes of Health Research; Leukemia Lymphoma Society of Canada; Charles Bruneau Foundation; Fonds de la Recherche en Sante du Quebec; Centre d'excellence en Oncologie pediatrique et en soins palliatifs; National Cancer Institute/NIH [P01 CA 68484] FX The authors thank all patients and their parents who consented to participate in genetics studies related to leukemia. Canadian Institutes of Health Research, Leukemia Lymphoma Society of Canada, Charles Bruneau Foundation, Fonds de la Recherche en Sante du Quebec, and Centre d'excellence en Oncologie pediatrique et en soins palliatifs supported this study. Dana-Farber Cancer Institute ALL treatment protocols are supported by the National Cancer Institute/NIH grant P01 CA 68484. NR 55 TC 9 Z9 11 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 SEP 15 PY 2013 VL 19 IS 18 BP 5240 EP 5249 DI 10.1158/1078-0432.CCR-13-1215 PG 10 WC Oncology SC Oncology GA 219NF UT WOS:000324513000034 PM 23908358 ER PT J AU Li, X Strle, K Wang, P Acosta, DI McHugh, GA Sikand, N Strle, F Steere, AC AF Li, Xin Strle, Klemen Wang, Peng Acosta, David I. McHugh, Gail A. Sikand, Nikhil Strle, Franc Steere, Allen C. TI Tick-Specific Borrelial Antigens Appear to Be Upregulated in American but Not European Patients With Lyme Arthritis, a Late Manifestation of Lyme Borreliosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Lyme borreliosis; Borrelia burgdorferi; antibody response; tick; OspA; OspD; BicA ID SURFACE PROTEIN-A; ANTIBIOTIC-REFRACTORY ARTHRITIS; WHOLE-GENOME SEQUENCES; DISEASE SPIROCHETE; ANTIBODY-RESPONSE; LIFE-CYCLE; BURGDORFERI; OSPA; MICE; INFLAMMATION AB Borrelia burgdorferi (Bb) sensu lato, the etiologic agent of Lyme borreliosis, adapts to distinct environments in the mammalian host and the tick vector by differential gene expression. As a result, infected mice are not exposed to and rarely make antibodies to the set of antigens that are preferentially expressed in the tick, including outer surface protein A (OspA), Borrelia iron and copper-binding protein A (BicA), and OspD. Surprisingly, however, antibodies to OspA and BicA have been noted in American patients with Lyme arthritis. Here, we examined serum samples from 210 American patients and 66 European patients with a range of early or late manifestations of Lyme borreliosis and found that only American patients with Lyme arthritis commonly had antibody responses to OspA, BicA, and OspD. This suggests that infection with American but not European Borrelia strains often leads to concerted upregulation or derepression of tick-specific spirochetal antigens in these patients. C1 [Li, Xin; Wang, Peng; Acosta, David I.] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. [Strle, Klemen; McHugh, Gail A.; Sikand, Nikhil; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA USA. [Strle, Klemen; Strle, Franc] Univ Med Ctr Ljubljana, Ljubljana, Slovenia. RP Li, X (reprint author), Ohio State Univ, Dept Vet Biosci, 1900 Coffey Rd,VMAB 344, Columbus, OH 43210 USA. EM xin.li@cvm.osu.edu FU National Institutes of Health [AI-110175, AR-20358, AR-062098]; Centers for Disease Control and Prevention [CCU110 291]; Arthritis Foundation; English, Bonter, Mitchell Foundation; Eshe Fund; Massachusetts General Hospital; Slovenian Research Agency [P3-0296] FX This work was supported in part by the National Institutes of Health (AI-110175 and AR-20358 to A. C. S.; AR-062098 to K. S.); Centers for Disease Control and Prevention (CCU110 291 to A. C. S); the Arthritis Foundation (Arthritis Investigator Award to X. L.; Postdoctoral Fellowship to K. S.); the English, Bonter, Mitchell Foundation (A. C. S.); the Eshe Fund (A. C. S.); Massachusetts General Hospital (Lyme Disease and Arthritis Research Fund to A. C. S.; Claflin Award to X. L.); and the Slovenian Research Agency (P3-0296 to F. S.). NR 50 TC 2 Z9 2 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2013 VL 208 IS 6 BP 934 EP 941 DI 10.1093/infdis/jit269 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 219MD UT WOS:000324510200010 PM 23766526 ER PT J AU Kraft, S Jouvin, MH Kulkarni, N Kissing, S Morgan, ES Dvorak, AM Schroder, B Saftig, P Kinet, JP AF Kraft, Stefan Jouvin, Marie-Helene Kulkarni, Nitin Kissing, Sandra Morgan, Ellen S. Dvorak, Ann M. Schroeder, Bernd Saftig, Paul Kinet, Jean-Pierre TI The Tetraspanin CD63 Is Required for Efficient IgE-Mediated Mast Cell Degranulation and Anaphylaxis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; FC-EPSILON-RI; CLASS-II MOLECULES; SECRETORY GRANULES; MEMBRANE-PROTEIN; HIGH-AFFINITY; MONOCLONAL-ANTIBODY; ANTIGEN ME491; IN-VIVO; ACTIVATION AB Mast cell (MC) activation through the high-affinity IgE receptor Fc epsilon RI leads to the release of mediators involved in immediate-type allergic reactions. Although Abs against the tetraspanins CD63 and CD81 inhibit Fc epsilon RI-induced MC degranulation, the intrinsic role of these molecules in Fc epsilon RI-induced MC activation is unknown. In MCs, CD63 is expressed at the cell surface and in lysosomes (particularly secretory lysosomes that contain allergic mediators). In this study, we investigated the role of CD63 in MC using a CD63 knockout mouse model. CD63-deficiency did not affect in vivo MC numbers and tissue distribution. Bone marrow-derived MC developed normally in the absence of CD63 protein. However, CD63-deficient bone marrow-derived MC showed a significant decrease in Fc epsilon RI-mediated degranulation, but not PMA/ionomycin-induced degranulation, as shown by beta-hexosaminidase release assays. The secretion of TNF-alpha, which is both released from granules and synthesized de novo upon MC activation, was also decreased. IL-6 secretion and production of the lipid mediator leukotriene C-4 were unaffected. There were no ultrastructural differences in granule content and morphology, late endosomal/lysosomal marker expression, Fc epsilon RI-induced global tyrosine phosphorylation, and Akt phosphorylation. Finally, local reconstitution in genetically MC-deficient Kit(w/w-v) mice was unaffected by the absence of CD63. However, the sites reconstituted with CD63-deficient MC developed significantly attenuated cutaneous anaphylactic reactions. These findings demonstrate that the absence of CD63 results in a significant decrease of MC degranulation, which translates into a reduction of acute allergic reactions in vivo, thus identifying CD63 as an important component of allergic inflammation. C1 [Kraft, Stefan; Jouvin, Marie-Helene; Kulkarni, Nitin; Kinet, Jean-Pierre] Beth Israel Deaconess Med Ctr, Dept Pathol, Lab Allergy & Immunol, Boston, MA 02215 USA. [Kraft, Stefan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kissing, Sandra; Schroeder, Bernd; Saftig, Paul] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany. [Morgan, Ellen S.; Dvorak, Ann M.] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02215 USA. RP Kinet, JP (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Lab Allergy & Immunol, 99 Brookline Ave, Boston, MA 02215 USA. EM psaftig@biochem.uni-kiel.de; jkinet@bidmc.harvard.edu RI Schroder, Bernd/C-5504-2011; Saftig, Paul/A-7966-2010 FU National Institutes of Health [RO1 AI41087]; Deutsche Forschungsgemeinschaft [DFG-GRK1459, SPP1580]; Center of Excellence Inflammation at Interfaces FX This work was supported by National Institutes of Health Grant RO1 AI41087 (to J.-P.K.) and grants from the Deutsche Forschungsgemeinschaft (DFG-GRK1459 and SPP1580) and the Center of Excellence Inflammation at Interfaces (to B. S. and P.S.). NR 48 TC 12 Z9 14 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2013 VL 191 IS 6 BP 2871 EP 2878 DI 10.4049/jimmunol.1202323 PG 8 WC Immunology SC Immunology GA 215JV UT WOS:000324206900004 PM 23945142 ER PT J AU Fogli, LK Sundrud, MS Goel, S Bajwa, S Jensen, K Derudder, E Sun, A Coffre, M Uyttenhove, C Van Snick, J Schmidt-Supprian, M Rao, A Grunig, G Durbin, J Casola, SS Rajewsky, K Koralov, SB AF Fogli, Laura K. Sundrud, Mark S. Goel, Swati Bajwa, Sofia Jensen, Kari Derudder, Emmanuel Sun, Amy Coffre, Maryaline Uyttenhove, Catherine Van Snick, Jacques Schmidt-Supprian, Marc Rao, Anjana Grunig, Gabriele Durbin, Joan Casola, Stefano S. Rajewsky, Klaus Koralov, Sergei B. TI T Cell-Derived IL-17 Mediates Epithelial Changes in the Airway and Drives Pulmonary Neutrophilia SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ROR-GAMMA-T; GM-CSF; CYTOKINES IL-17A; T(H)17 CELLS; MURINE MODEL; INFLAMMATION; ASTHMA; EXPRESSION; SPUTUM; STAT3 AB Th17 cells are a proinflammatory subset of effector T cells that have been implicated in the pathogenesis of asthma. Their production of the cytokine IL-17 is known to induce local recruitment of neutrophils, but the direct impact of IL-17 on the lung epithelium is poorly understood. In this study, we describe a novel mouse model of spontaneous IL-17-driven lung inflammation that exhibits many similarities to asthma in humans. We have found that STAT3 hyperactivity in T lymphocytes causes an expansion of Th17 cells, which home preferentially to the lungs. IL-17 secretion then leads to neutrophil infiltration and lung epithelial changes, in turn leading to a chronic inflammatory state with increased mucus production and decreased lung function. We used this model to investigate the effects of IL-17 activity on airway epithelium and identified CXCL5 and MIP-2 as important factors in neutrophil recruitment. The neutralization of IL-17 greatly reduces pulmonary neutrophilia, underscoring a key role for IL-17 in promoting chronic airway inflammation. These findings emphasize the role of IL-17 in mediating neutrophil-driven pulmonary inflammation and highlight a new mouse model that may be used for the development of novel therapies targeting Th17 cells in asthma and other chronic pulmonary diseases. C1 [Fogli, Laura K.; Goel, Swati; Bajwa, Sofia; Sun, Amy; Coffre, Maryaline; Durbin, Joan; Koralov, Sergei B.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Sundrud, Mark S.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA. [Goel, Swati] NYU, Sch Med, Dept Hematol Oncol, New York, NY 10016 USA. [Jensen, Kari; Rajewsky, Klaus] Immune Dis Inst, Boston, MA 02115 USA. [Derudder, Emmanuel] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. [Uyttenhove, Catherine; Van Snick, Jacques] Ludwig Inst, B-1200 Brussels, Belgium. [Schmidt-Supprian, Marc] Max Delbruck Ctr Biochem, D-82152 Munich, Germany. [Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA. [Grunig, Gabriele] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA. [Casola, Stefano S.] Italian Fdn Canc Res, Inst Mol Oncol, I-20139 Milan, Italy. RP Koralov, SB (reprint author), NYU, Sch Med, Dept Pathol, 550 1st Ave, New York, NY 10016 USA. EM sergei.koralov@nyumc.org RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 FU New York University Vittorio Defendi Fellowship; GlaxoSmithKline/Immune Disease Institute; National Institutes of Health [CA42471, AI40127, 1R01 HL095764-01]; New York University Whitehead Fellowship; a Feinberg Lymphoma Grant; Concern Foundation; Cancer Center Support Grant for Shared Resources to New York University Cancer Institute, NCI [2P30CA016087-33] FX L.K.F. was supported by a New York University Vittorio Defendi Fellowship. M. S. S., K. R., and S. B. K. were supported by the GlaxoSmithKline/Immune Disease Institute alliance grant. A. R. was supported by National Institutes of Health Grants CA42471 and AI40127. G. G. was supported by National Institutes of Health Grant 1R01 HL095764-01. S. B. K. was supported by a New York University Whitehead Fellowship, a Feinberg Lymphoma Grant, and the Concern Foundation. L. K. F. and S. B. K. acknowledge the support of Cancer Center Support Grant for Shared Resources to New York University Cancer Institute, NCI 2P30CA016087-33. NR 52 TC 28 Z9 31 U1 0 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2013 VL 191 IS 6 BP 3100 EP 3111 DI 10.4049/jimmunol.1301360 PG 12 WC Immunology SC Immunology GA 215JV UT WOS:000324206900028 PM 23966625 ER PT J AU Kamel, G Hoyos, T Rochard, L Dougherty, M Kong, Y Tse, W Shubinets, V Grimaldi, M Liao, EC AF Kamel, George Hoyos, Tatiana Rochard, Lucie Dougherty, Max Kong, Yawei Tse, William Shubinets, Valeriy Grimaldi, Michael Liao, Eric C. TI Requirement for frzb and fzd7a in cranial neural crest convergence and extension mechanisms during zebrafish palate and jaw morphogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Convergence extension; wnt; frizzled; frzb; fzd7a; Wnt9a; Cranial neural crest; Craniofacial; Zebrafish ID PHARYNGEAL ARCH DEVELOPMENT; NONSYNDROMIC CLEFT-LIP; PLANAR CELL POLARITY; CRANIOFACIAL DEVELOPMENT; GASTRULATION MOVEMENTS; EMBRYONIC-DEVELOPMENT; VENTRICULAR SEPTUM; SIGNALING PATHWAY; HOX EXPRESSION; FRIZZLED 2 AB Regulation of convergence and extension by wnt-frizzled signaling is a common theme in embryogenesis. This study examines the functional requirements of frzb and fzd7a in convergence and extension mechanisms during craniofacial development. Using a morpholino knockdown approach, we found that frzb and fzd7a are dispensable for directed migration of the bilateral trabeculae, but necessary for the convergence and extension of the palatal elements, where the extension process is mediated by chondrocyte proliferation, morphologic change and intercalation. In contrast, frzb and fzd7a are required for convergence of the mandibular prominences, where knockdown of either frzb or fzd7a resulted in complete loss of lower jaw structures. Further, we found that bapx1 was specifically downregulated in the wnt9a/frzb/fzd7a morphants, while general neural crest markers were unaffected. In addition, expression of wnt9a and frzb was also absent in the edn-/- mutant. Notably, over-expression of bapx1 was sufficient to partially rescue mandibular elements in the wnt9a/frzb/fzd7a morphants, demonstrating genetic epistasis of bapx1 acting downstream of edn1 and wnt9a/frzb/fzd7a in lower jaw development. This study underscores the important role of wnt-frizzled signaling in convergence and extension in palate and craniofacial morphogenesis, distinct regulation of upper vs. lower jaw structures, and integration of wnt-frizzled with endothelin signaling to coordinate shaping of the facial form. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kamel, George; Hoyos, Tatiana; Rochard, Lucie; Dougherty, Max; Kong, Yawei; Tse, William; Shubinets, Valeriy; Grimaldi, Michael; Liao, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Kamel, George; Hoyos, Tatiana; Rochard, Lucie; Dougherty, Max; Kong, Yawei; Tse, William; Shubinets, Valeriy; Grimaldi, Michael; Liao, Eric C.] Harvard Univ, Sch Med, MA Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA USA. [Liao, Eric C.] Harvard Stem Cell Inst, Boston, MA USA. RP Liao, EC (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,CPZN 4256, Boston, MA 02114 USA. EM cliao@partners.org RI TSE, KA FAI WILLIAM/C-9384-2012 OI TSE, KA FAI WILLIAM/0000-0002-3738-0460 FU March of Dimes Basil O'Connor Starter Scholar Award; Shriners Hospital for Children; American Surgical Association Research Fellowship; Plastic Surgery Foundation FX We are grateful to Renee Ethier for excellent management of our aquatics facility and all members of the laboratory for helpful discussions. This work was funded by the March of Dimes Basil O'Connor Starter Scholar Award, Shriners Hospital for Children, American Surgical Association Research Fellowship and the Plastic Surgery Foundation. NR 76 TC 16 Z9 17 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2013 VL 381 IS 2 BP 423 EP 433 DI 10.1016/j.ydbio.2013.06.012 PG 11 WC Developmental Biology SC Developmental Biology GA 212ON UT WOS:000323992800011 PM 23806211 ER PT J AU Li, AR Ahsen, OO Liu, JJ Du, C McKee, ML Yang, Y Wasco, W Newton-Cheh, CH O'Donnell, CJ Fujimoto, JG Zhou, C Tanzi, RE AF Li, Airong Ahsen, Osman O. Liu, Jonathan J. Du, Chuang McKee, Mary L. Yang, Yan Wasco, Wilma Newton-Cheh, Christopher H. O'Donnell, Christopher J. Fujimoto, James G. Zhou, Chao Tanzi, Rudolph E. TI Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography SO HUMAN MOLECULAR GENETICS LA English DT Article ID VENTRICULAR DIASTOLIC FUNCTION; GENOME-WIDE ASSOCIATION; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; RETINAL BLOOD-FLOW; HYPERTROPHIC CARDIOMYOPATHY; ATRIAL-FIBRILLATION; FILLING PRESSURE; PROGNOSTIC VALUE; GENE-EXPRESSION AB The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits. C1 [Li, Airong; Yang, Yan; Wasco, Wilma; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [McKee, Mary L.] Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. [Newton-Cheh, Christopher H.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. [Ahsen, Osman O.; Liu, Jonathan J.; Fujimoto, James G.; Zhou, Chao] MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA. [Du, Chuang] Tufts Univ, Sch Med, Ctr Neurosci Res, Boston, MA 02111 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Zhou, Chao] Lehigh Univ, Dept Elect & Comp & Engn, Bethlehem, PA 18015 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM chaozhou@lehigh.edu; tanzi@helix.mgh.harvard.edu RI Zhou, Chao/A-1327-2007; Ahsen, Osman/K-4524-2015 OI Ahsen, Osman/0000-0003-4811-3429 FU Cure Alzheimer's Fund; National Institute of Health [R01AG014713, R01MH60009, R01CA75289, R01HL095717, R00EB010071, R03AR063271]; Air Force Office of Scientific Research [FA9550-07-1-0014]; Massachusetts General Hospital ECOR Award; Boston Area Diabetes and Endocrinology Research Center [DK 57521]; Center for the Study of Inflammatory Bowel Disease [DK 43351] FX This work was supported by the Cure Alzheimer's Fund to R. E. T., the National Institute of Health (R01AG014713 and R01MH60009 to R. E. T.; R01CA75289 and R01HL095717 to J.G.F.; R00EB010071 to C.Z.; R03AR063271 to A. L.), the Air Force Office of Scientific Research (FA9550-07-1-0014 to J.G.F.) and a Massachusetts General Hospital ECOR Award to A. L. The Microscopy Core Facility at the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK 57521) and the Center for the Study of Inflammatory Bowel Disease (DK 43351). NR 81 TC 5 Z9 5 U1 2 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 15 PY 2013 VL 22 IS 18 BP 3798 EP 3806 DI 10.1093/hmg/ddt230 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 207FD UT WOS:000323582000015 PM 23696452 ER PT J AU Klein, AP Lindstrom, S Mendelsohn, JB Steplowski, E Arslan, AA Bueno-de-Mesquita, HB Fuchs, CS Gallinger, S Gross, M Helzlsouer, K Holly, EA Jacobs, EJ LaCroix, A Li, DH Mandelson, MT Olson, SH Petersen, GM Risch, HA Stolzenberg-Solomon, RZ Zheng, W Amundadottir, L Albanes, D Allen, NE Bamlet, WR Boutron-Ruault, MC Buring, JE Bracci, PM Canzian, F Clipp, S Cotterchio, M Duell, EJ Elena, J Gaziano, JM Giovannucci, EL Goggins, M Hallmans, G Hassan, M Hutchinson, A Hunter, DJ Kooperberg, C Kurtz, RC Liu, SM Overvad, K Palli, D Patel, AV Rabe, KG Shu, XO Slimani, N Tobias, GS Trichopoulos, D Van den Eeden, SK Vineis, P Virtamo, J Wactawski-Wende, J Wolpin, BM Yu, H Yu, K Zeleniuch-Jacquotte, A Chanock, SJ Hoover, RN Hartge, P Kraft, P AF Klein, Alison P. Lindstroem, Sara Mendelsohn, Julie B. Steplowski, Emily Arslan, Alan A. Bueno-de-Mesquita, H. Bas Fuchs, Charles S. Gallinger, Steven Gross, Myron Helzlsouer, Kathy Holly, Elizabeth A. Jacobs, Eric J. LaCroix, Andrea Li, Donghui Mandelson, Margaret T. Olson, Sara H. Petersen, Gloria M. Risch, Harvey A. Stolzenberg-Solomon, Rachael Z. Zheng, Wei Amundadottir, Laufey Albanes, Demetrius Allen, Naomi E. Bamlet, William R. Boutron-Ruault, Marie-Christine Buring, Julie E. Bracci, Paige M. Canzian, Federico Clipp, Sandra Cotterchio, Michelle Duell, Eric J. Elena, Joanne Gaziano, J. Michael Giovannucci, Edward L. Goggins, Michael Hallmans, Goeran Hassan, Manal Hutchinson, Amy Hunter, David J. Kooperberg, Charles Kurtz, Robert C. Liu, Simin Overvad, Kim Palli, Domenico Patel, Alpa V. Rabe, Kari G. Shu, Xiao-Ou Slimani, Nadia Tobias, Geoffrey S. Trichopoulos, Dimitrios Van den Eeden, Stephen K. Vineis, Paolo Virtamo, Jarmo Wactawski-Wende, Jean Wolpin, Brian M. Yu, Herbert Yu, Kai Zeleniuch-Jacquotte, Anne Chanock, Stephen J. Hoover, Robert N. Hartge, Patricia Kraft, Peter TI An Absolute Risk Model to Identify Individuals at Elevated Risk for Pancreatic Cancer in the General Population SO PLOS ONE LA English DT Article ID COHORT-CONSORTIUM PANSCAN; GENOME-WIDE ASSOCIATION; ABO BLOOD-GROUP; POOLED-ANALYSIS; FAMILY-HISTORY; HEREDITARY PANCREATITIS; GENETIC EPIDEMIOLOGY; SUSCEPTIBILITY; METAANALYSIS; MUTATIONS AB Purpose: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. Patients and Methods: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. Results: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U. S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. Conclusion: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors. C1 [Klein, Alison P.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21218 USA. [Klein, Alison P.] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA. [Klein, Alison P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lindstroem, Sara; Giovannucci, Edward L.; Hunter, David J.; Trichopoulos, Dimitrios; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lindstroem, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Mendelsohn, Julie B.; Stolzenberg-Solomon, Rachael Z.; Amundadottir, Laufey; Albanes, Demetrius; Tobias, Geoffrey S.; Yu, Kai; Chanock, Stephen J.; Hoover, Robert N.; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Helzlsouer, Kathy] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Helzlsouer, Kathy] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Holly, Elizabeth A.; Bracci, Paige M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [LaCroix, Andrea; Mandelson, Margaret T.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Li, Donghui; Hassan, Manal] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Mandelson, Margaret T.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Petersen, Gloria M.; Bamlet, William R.; Rabe, Kari G.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Risch, Harvey A.; Yu, Herbert] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06510 USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. [Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Allen, Naomi E.] UK Biobank, Oxford, England. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Cotterchio, Michelle] Canc Care Ontario, Toronto, ON, Canada. [Cotterchio, Michelle] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain. [Elena, Joanne] NCI, Div Canc Control & Populat Sci, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hutchinson, Amy] NCI Frederick, SAIC Frederick Inc, Core Genotyping Facil, Frederick, MD USA. [Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Program Biostat & Biomath, Seattle, WA 98104 USA. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Liu, Simin] Univ Calif Los Angeles, Ctr Metab Dis Prevent, Dept Epidemiol, Los Angeles, CA USA. [Liu, Simin] Univ Calif Los Angeles, Dept Med, Ctr Metab Dis Prevent, Los Angeles, CA 90024 USA. [Liu, Simin] Univ Calif Los Angeles, Dept Obstet & Gynecol, Ctr Metab Dis Prevent, Los Angeles, CA 90024 USA. [Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, Aarhus, Denmark. [Palli, Domenico] ISPO Florence, Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Slimani, Nadia] Int Agcy Res Canc, F-69372 Lyon, France. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Van den Eeden, Stephen K.] Kaiser Permanente, Div Res, Northern Calif Reg, Oakland, CA USA. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Klein, AP (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21218 USA. EM aklein1@jhmi.edu RI Gallinger, Steven/E-4575-2013; Liu, Simin/I-3689-2014; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Liu, Simin/0000-0003-2098-3844; Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163; PALLI, Domenico/0000-0002-5558-2437; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI [R01CA034588, R01CA098661, P30CA016087, P50CA62924, R01CA97075, NO1-CN-25514, NO1-CN-25522, NO1-CN-25515, NO1-CN-25512, NO1-CN-25513, NO1-CN-25516, NO1-CN-25511, NO1-CN-25524, NO1-CN-25518, NO1-CN-75022, NO1-CN-25476, NO1-CN-25404]; National Institute of Environmental Health Sciences [ES000260]; National Heart, Lung, and Blood Institute, NIH [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Mayo Clinic SPORE in Pancreatic Cancer [P50 CA102701]; NCI, NIH [5R01CA098870, P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, RO1 CA97193, RO1 CA34944, RO1 CA40360, RO1 HL26490, RO1 HL34595, RO1 CA047988, RO1 HL043851, RO1 HL080467]; Lustgarten Foundation for Pancreatic Cancer Research; National Cancer Institute extramural research grant [R01 CA82729, R37 CA70867]; Intramural Research Program of National Cancer Institute (Division of Cancer Epidemiology and Genetics); NIH [RO1 CA98380]; National Cancer Institute [CA59706, CA108370, CA109767, CA89726, CA98889]; Rombauer Pancreatic Cancer Research Fund; NIH as part of the PACGENE consortium [R01 CA97075]; Intramural Research Program of the NCI, NIH, and through U.S. Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004] FX The NYU Women's Health Study is supported by research grants R01CA034588, R01CA098661, center grant P30CA016087 from the NCI and the center grant ES000260 from the National Institute of Environmental Health Sciences. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The Mayo Clinic Molecular Epidemiology of Pancreatic Cancer study is supported by the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701). The authors would like to acknowledge Traci Hammer, Jodi Cogswell, Hugues Sicotte, Ann Oberg, Janet Olson, Martha Matsumoto, and Dennis Robinson. The Yale University study was supported by grant number 5R01CA098870 from the NCI, NIH. The cooperation of 30 Connecticut hospitals, including Stamford Hospital, in allowing patient access, is gratefully acknowledged. This study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in this study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. The PHS, NHS, HPFS and WHS at Harvard were supported by the NCI, NIH (Grants No. P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, RO1 CA97193, RO1 CA34944, RO1 CA40360, RO1 HL26490, RO1 HL34595, RO1 CA047988, RO1 HL043851, RO1 HL080467). The work at Johns Hopkins University was supported by the NCI (Grants P50CA62924 and R01CA97075) and the Lustgarten Foundation for Pancreatic Cancer Research. The Shanghai Men's Health Study was supported by the National Cancer Institute extramural research grant [R01 CA82729]. The Shanghai Women's Health Study was supported by the National Cancer Institute extramural research grant [R37 CA70867] and, partially for biological sample collection, by the Intramural Research Program of National Cancer Institute (Division of Cancer Epidemiology and Genetics). The authors are in debt to the contributions of Drs. Yu-Tang Gao and Yong-Bing Xiang in these two cohort studies. The studies would not be possible without the continuing support and devotion from the study participants and staff of the SMHS and SWHS. Memorial Sloan Kettering Cancer Center acknowledges the work of Jennifer A. Simon and Irene Orlow. The work at MD Anderson was supported by NIH grant RO1 CA98380. The UCSF study was supported in part by National Cancer Institute grants CA59706, CA108370, CA109767, CA89726 (E. A. Holly, PI) and CA98889 (E. J. Duell, PI) and by the Rombauer Pancreatic Cancer Research Fund. The University of Toronto study was supported by grants from the NIH (R01 CA97075, as part of the PACGENE consortium), The Lustgarten Foundation for Pancreatic Cancer Research and the Ontario Cancer Research Network. The authors acknowledge the Pancreatic Cancer Canada Foundation (www.pancreaticcancercanada.ca) for their continued support of research into the early detection of pancreatic cancer, and the Pancreas Cancer Screening Study at Mount Sinai Hospital and Princess Margaret Hospital. The authors acknowledge Ayelet Borgida and Heidi Rothenmund for their dedicated contributions towards data collection and study co-ordination.; PLCO was supported by individual contracts from the NCI to the University of Colorado Denver NO1-CN-25514, Georgetown University NO1-CN-25522, Pacific Health Research Institute NO1-CN-25515, Henry Ford Health System NO1-CN-25512, University of Minnesota, NO1-CN-25513, Washington University NO1-CN-25516, University of Pittsburgh NO1-CN-25511, University of Utah NO1-CN-25524, Marshfield Clinic Research Foundation NO1-CN-25518, University of Alabama at Birmingham NO1-CN-75022, Westat, Inc. NO1-CN-25476, University of California, Los Angeles NO1-CN-25404. The ATBC Study was supported by funding provided by the Intramural Research Program of the NCI, NIH, and through U.S. Public Health Service contracts (N01-CN-45165, N01-RC-45035, and N01-RC-37004) from the NCI. For the EPIC cohorts, all coauthors coordinated the initial recruitment and management of the studies. The authors thank all of the participants who took part in this research and the funders and support and technical staff who made this study possible. The work described in this paper was carried out with the support of the European Commission: Public Health and Consumer Protection Directorate 1993-2004; Research Directorate-General 2005-."; Ligue contre le Cancer, Societe 3M, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); ISCIII RETIC (RD06/0020) of the Spanish Ministry of Health, The participating regional governments and institutions (Spain); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (United Kingdom); Greek Ministry of Health and Social Solidarity, Hellenic Health Foundation and Stavros Niarchos Foundation (Greece); Italian Association for Research on Cancer (AIRC) (Italy); Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (the Netherlands); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Vasterbotten (Sweden). CLUE II was supported by National Institute of Aging grant (5U01AG018033) and National Cancer Institute grants (CA105069, CA73790). The authors express their appreciation to the participants of the CLUE II cohort and thank the staff at the George W. Comstock Center for Public Health Research and Prevention for their dedication and contributions to the study: Judy HoffmanBolton, Clara Krumpe, Kitty Spoonire and Betty Miner. The Cancer Prevention Study II Nutrition Cohort is supported by the American Cancer Society. The authors thank all of the men and women in the Cancer Prevention Study II Nutrition Cohort for their many years of dedicated participation in the study. The authors wish to thank Debbie Winn, Daniela Seminara and Scott Rogers for assisting with funding coordination for the project and Donghui Li for supporting the study with supplemental grant CA98380. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government.; The authors acknowledge the contribution of the staff of the Core Genotyping Facility, specifically, Zhaoming Wang, Chenwei Liu, Xiang Deng, Laurie Burdett, Aurelie Vogt, and Belynda Hicks. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 37 Z9 39 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 13 PY 2013 VL 8 IS 9 AR e72311 DI 10.1371/journal.pone.0072311 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 218BU UT WOS:000324408400005 PM 24058443 ER PT J AU Shi, Z Hayes, G Ruvkun, G AF Shi, Zhen Hayes, Gabriel Ruvkun, Gary TI Dual Regulation of the lin-14 Target mRNA by the lin-4 miRNA SO PLOS ONE LA English DT Article ID HETEROCHRONIC GENE LIN-14; POSTEMBRYONIC DEVELOPMENTAL EVENTS; CAENORHABDITIS-ELEGANS; TRANSLATIONAL REPRESSION; C-ELEGANS; PROTEIN-SYNTHESIS; MICRORNA TARGETS; INITIATION; DECAY; EXPRESSION AB microRNAs (miRNAs) are similar to 22 nt regulatory RNAs that in animals typically bind with partial complementarity to sequences in the 39 untranslated (UTR) regions of target mRNAs, to induce a decrease in the production of the encoded protein. The relative contributions of translational inhibition of intact mRNAs and degradation of mRNAs caused by binding of the miRNA vary; for many genetically validated miRNA targets, translational repression has been implicated, whereas some analyses of other miRNA targets have revealed only modest translational repression and more significant mRNA destabilization. In Caenorhabditis elegans, the lin-4 miRNA accumulates during early larval development, binds to target elements in the lin-14 mRNA, and causes a sharp decrease in the abundance of LIN-14 protein. Here, we monitor the dynamics of lin-14 mRNA and protein as well as lin-4 miRNA levels in finely staged animals during early larval development. We find complex regulation of lin-14, with the abundance of lin-14 mRNA initially modestly declining followed by fluctuation but little further decline of lin-14 mRNA levels accompanied by continuing and more dramatic decline in LIN-14 protein abundance. We show that the translational inhibition of lin-14 is dependent on binding of the lin-4 miRNA to multiple lin-4 complementary sites in the lin-14 3'UTR. Our results point to the importance of translational inhibition in silencing of lin-14 by the lin-4 miRNA. C1 [Shi, Zhen; Hayes, Gabriel; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Shi, Zhen] Harvard Univ, Sch Med, Biol Sci Dent Med Program, Boston, MA USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIH [R01-GM44619] FX This work was supported by a grant from the NIH to G. R. (R01-GM44619). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. NR 26 TC 0 Z9 0 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 13 PY 2013 VL 8 IS 9 AR e75475 DI 10.1371/journal.pone.0075475 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 218BU UT WOS:000324408400115 PM 24058689 ER PT J AU Apps, R Carrington, M AF Apps, Richard Carrington, Mary TI Response to Comment on "Influence of HLA-C Expression Level on HIV Control" SO SCIENCE LA English DT Editorial Material ID SURFACE EXPRESSION; ASSOCIATION; BINDING C1 [Apps, Richard; Carrington, Mary] Sci Applicat Int Corp Frederick Inc, Canc & Inflammat Program, Lab Expt Immunol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Apps, Richard; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Apps, Richard; Carrington, Mary] Harvard Univ, Cambridge, MA 02139 USA. RP Carrington, M (reprint author), Sci Applicat Int Corp Frederick Inc, Canc & Inflammat Program, Lab Expt Immunol, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM carringm@mail.nih.gov NR 9 TC 1 Z9 1 U1 1 U2 26 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 13 PY 2013 VL 341 IS 6151 DI 10.1126/science.1241854 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215ZA UT WOS:000324248800020 PM 24031003 ER PT J AU Zurzolo, GA Allen, KJ Taylor, SL Shreffler, WG Baumert, JL Tang, MLK Gurrin, LC Mathai, ML Nordlee, JA DunnGalvin, A Hourihane, JO AF Zurzolo, Giovanni A. Allen, Katrina J. Taylor, Steve L. Shreffler, Wayne G. Baumert, Joseph L. Tang, Mimi L. K. Gurrin, Lyle C. Mathai, Michael L. Nordlee, Julie A. DunnGalvin, Audrey Hourihane, Jonathan O'B TI Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a novel single-dose challenge protocol SO ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY LA English DT Article DE Eliciting dose (ED); Food Allergy related Quality of Life Questionnaires-(FAQLQ); Single dose; Peanut thresholds; Oral Food Challenges (OFC); Voluntary Incidental Trace Allergen Labelling (VITAL); Peanut Allergen Threshold Study (PATS) ID ORAL FOOD CHALLENGES; RISK-ASSESSMENT; DOUBLE-BLIND; FRAMEWORK; VALIDITY; WORKSHOP; CHILDREN AB Background: The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients' threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals. Methods/Aims: This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children's Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre. A total of 375 participants, aged 1-18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed. Conclusion: The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population. C1 [Zurzolo, Giovanni A.; Allen, Katrina J.; Tang, Mimi L. K.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Zurzolo, Giovanni A.; Mathai, Michael L.] Victoria Univ, Sch Biomed & Hlth Sci, Biomed & Lifestyle Dis Unit, Melbourne, Vic 8001, Australia. [Allen, Katrina J.; Tang, Mimi L. K.] Royal Childrens Hosp, Dept Allergy & Immunol, Melbourne, Vic, Australia. [Allen, Katrina J.; Tang, Mimi L. K.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Taylor, Steve L.; Baumert, Joseph L.; Nordlee, Julie A.] Univ Nebraska, Food Allergy Res & Resource Program, Lincoln, NE USA. [Shreffler, Wayne G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Food Allergy Ctr, Boston, MA USA. [Shreffler, Wayne G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Gurrin, Lyle C.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. [DunnGalvin, Audrey; Hourihane, Jonathan O'B] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. RP Hourihane, JO (reprint author), Natl Univ Ireland Univ Coll Cork, Cork, Ireland. EM J.Hourihane@ucc.ie OI Zurzolo, Giovanni/0000-0003-0230-0691; Allen, Katrina/0000-0002-1921-4493 FU Food Allergy Research & Resource Program (FARRP); Victorian Government's Operational Infrastructure Support Program; Victoria University FX This project is funded by Food Allergy Research & Resource Program (FARRP). Dr Dean Tey who is a consultant Paediatrician at the Department of Allergy at the Royal Children's Hospital Melbourne for his contribution to the manuscript. The Murdoch Childrens Research Institute is supported by funding from the Victorian Government's Operational Infrastructure Support Program. Also to Victoria University for providing funding for the publishing of this manuscript. NR 21 TC 8 Z9 8 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1710-1484 EI 1710-1492 J9 ALLERGY ASTHMA CL IM JI Allerg Asthma Clin. Immunol. PD SEP 12 PY 2013 VL 9 AR 35 DI 10.1186/1710-1492-9-35 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA AC3JA UT WOS:000332412300001 PM 24028324 ER PT J AU Peisley, A Wu, B Yao, H Walz, T Hur, S AF Peisley, Alys Wu, Bin Yao, Hui Walz, Thomas Hur, Sun TI RIG-I Forms Signaling-Competent Filaments in an ATP-Dependent, Ubiquitin-Independent Manner SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRANDED-RNA; INNATE IMMUNE-RESPONSE; INDUCIBLE GENE-I; STRUCTURAL BASIS; PATTERN-RECOGNITION; DSRNA RECOGNITION; MDA5 FILAMENTS; INFECTED-CELLS; VIRAL-RNA; ACTIVATION AB Retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are paralogous receptors for viral double-stranded RNA (dsRNA) with divergent specificity. We have previously shown that MDA5 forms filaments upon viral dsRNA recognition and that this filament formation is essential for interferon signal activation. Here, we show that while RIG-I binds to a dsRNA end as a monomer in the absence of ATP, it assembles in the presence of ATP into a filament that propagates from the dsRNA end to the interior. Furthermore, RIG-I filaments directly stimulate mitochondrial antiviral signaling (MAVS) filament formation without any cofactor, such as polyubiquitin chains, and forced juxtaposition of the isolated signaling domain of RIG-I, as it would be in the filament, is sufficient to activate interferon signaling. Our findings thus define filamentous architecture as a common yet versatile molecular platform for divergent viral RNA detection and proximity-induced signal activation by RIG-I and MDA5. C1 [Peisley, Alys; Wu, Bin; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Peisley, Alys; Wu, Bin; Yao, Hui; Hur, Sun] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yao, Hui] Nankai Univ, Dept Biochem & Mol Biol, Tianjin 300071, Peoples R China. [Walz, Thomas] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Hur, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM sun.hur@childrens.harvard.edu RI Wu, Bin/C-4715-2015 FU Pew Scholarship; Massachusetts Life Science Center New Investigator Award; Milton Foundation Fund FX B.W. is a GSK fellow. T.W. is an Investigator with the Howard Hughes Medical Institute. S.H. is a recipient of a Pew Scholarship, Massachusetts Life Science Center New Investigator Award, and Milton Foundation Fund. NR 34 TC 63 Z9 63 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD SEP 12 PY 2013 VL 51 IS 5 BP 573 EP 583 DI 10.1016/j.molcel.2013.07.024 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 296MP UT WOS:000330189500005 PM 23993742 ER PT J AU Agam, Y Carey, C Barton, JJS Dyckman, KA Lee, AKC Vangel, M Manoach, DS AF Agam, Yigal Carey, Caitlin Barton, Jason J. S. Dyckman, Kara A. Lee, Adrian K. C. Vangel, Mark Manoach, Dara S. TI Network Dynamics Underlying Speed-Accuracy Trade-Offs in Response to Errors SO PLOS ONE LA English DT Article ID EVENT-RELATED FMRI; POSTERIOR CINGULATE CORTEX; DEFAULT MODE NETWORK; FRONTAL EYE FIELD; FUNCTIONAL CONNECTIVITY; DECISION-MAKING; REACTION-TIME; HUMAN BRAIN; ATTENTION; TASKS AB The ability to dynamically and rapidly adjust task performance based on its outcome is fundamental to adaptive, flexible behavior. Over trials of a task, responses speed up until an error is committed and after the error responses slow down. These dynamic adjustments serve to optimize performance and are well-described by the speed-accuracy trade-off (SATO) function. We hypothesized that SATOs based on outcomes reflect reciprocal changes in the allocation of attention between the internal milieu and the task-at-hand, as indexed by reciprocal changes in activity between the default and dorsal attention brain networks. We tested this hypothesis using functional MRI to examine the pattern of network activation over a series of trials surrounding and including an error. We further hypothesized that these reciprocal changes in network activity are coordinated by the posterior cingulate cortex (PCC) and would rely on the structural integrity of its white matter connections. Using diffusion tensor imaging, we examined whether fractional anisotropy of the posterior cingulum bundle correlated with the magnitude of reciprocal changes in network activation around errors. As expected, reaction time (RT) in trials surrounding errors was consistent with predictions from the SATO function. Activation in the default network was: (i) inversely correlated with RT, (ii) greater on trials before than after an error and (iii) maximal at the error. In contrast, activation in the right intraparietal sulcus of the dorsal attention network was (i) positively correlated with RT and showed the opposite pattern: (ii) less activation before than after an error and (iii) the least activation on the error. Greater integrity of the posterior cingulum bundle was associated with greater reciprocity in network activation around errors. These findings suggest that dynamic changes in attention to the internal versus external milieu in response to errors underlie SATOs in RT and are mediated by the PCC. C1 [Agam, Yigal; Manoach, Dara S.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Agam, Yigal; Vangel, Mark; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Carey, Caitlin] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Barton, Jason J. S.] Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Ophthalmol, Vancouver, BC, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Visual Sci, Vancouver, BC V5Z 1M9, Canada. [Dyckman, Kara A.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Lee, Adrian K. C.] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. RP Agam, Y (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM yigal@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012; OI Lee, Adrian KC/0000-0002-7611-0500; Carey, Caitlin/0000-0002-4953-5351 FU National Institute for Mental Health [F32 MH088081, F32 MH082514, R01 MH67720] FX Funding came from the National Institute for Mental Health F32 MH088081 (YA); F32 MH082514 (KD); R01 MH67720 (DSM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 6 Z9 6 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 12 PY 2013 VL 8 IS 9 AR e73692 DI 10.1371/journal.pone.0073692 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242KO UT WOS:000326240100055 PM 24069223 ER PT J AU Colaneri, A Wang, TY Pagadala, V Kittur, J Staffa, NG Peddada, SD Isganaitis, E Patti, ME Birnbaumer, L AF Colaneri, Alejandro Wang, Tianyuan Pagadala, Vijayakanth Kittur, Jaya Staffa, Nickolas G., Jr. Peddada, Shyamal D. Isganaitis, Elvira Patti, Mary Elizabeth Birnbaumer, Lutz TI A Minimal Set of Tissue-Specific Hypomethylated CpGs Constitute Epigenetic Signatures of Developmental Programming SO PLOS ONE LA English DT Article ID LARGE GENE LISTS; DNA METHYLATION; ISLAND SHORES; GENOME; REVEALS; REGIONS; DISEASE; METHYLOME; CANCER; MOUSE AB Background: Cell specific states of the chromatin are programmed during mammalian development. Dynamic DNA methylation across the developing embryo guides a program of repression, switching off genes in most cell types. Thus, the majority of the tissue specific differentially methylated sites (TS-DMS) must be un-methylated CpGs. Methodology and Principal Findings: Comparison of expanded Methyl Sensitive Cut Counting data (eMSCC) among four tissues (liver, testes, brain and kidney) from three C57BL/6J mice, identified 138,052 differentially methylated sites of which 23,270 contain CpGs un-methylated in only one tissue (TS-DMS). Most of these CpGs were located in intergenic regions, outside of promoters, CpG islands or their shores, and up to 20% of them overlapped reported active enhancers. Indeed, tissue-specific enhancers were up to 30 fold enriched in TS-DMS. Testis showed the highest number of TS-DMS, but paradoxically their associated genes do not appear to be specific to the germ cell functions, but rather are involved in organism development. In the other tissues the differentially methylated genes are associated with tissue-specific physiological or anatomical functions. The identified sets of TS-DMS quantify epigenetic distances between tissues, generated during development. We applied this concept to measure the extent of reprogramming in the liver of mice exposed to in utero or early postnatal nutritional stress. Different protocols of food restriction reprogrammed the liver methylome in different but reproducible ways. Conclusion and Significance: Thus, each identified set of differentially methylated sites constituted an epigenetic signature that traced the developmental programing or the early nutritional reprogramming of each exposed mouse. We propose that our approach has the potential to outline a number of disease-associated epigenetic states. The composition of differentially methylated CpGs may vary with each situation, behaving as a composite variable, which can be used as a pre-symptomatic marker for disease. C1 [Colaneri, Alejandro; Wang, Tianyuan; Pagadala, Vijayakanth; Kittur, Jaya; Staffa, Nickolas G., Jr.; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. [Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Isganaitis, Elvira; Patti, Mary Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Colaneri, A (reprint author), Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. EM acolaneri_2000@yahoo.com.ar; birnbau1@niehs.nih.gov FU National Institutes of Health [Z01-ES-103006]; American Diabetes Association; Graetz Foundation; Lilly Foundation; Lawson-Wilkins Pediatric Endocrine Society; Joslin DERC [5P30 DK036836-23] FX This work was supported by the Intramural Research Program of the National Institutes of Health [2009 NIH Director's Challenge Award and Project Z01-ES-103006 to L. B.]. The authors gratefully acknowledge research grant support from the American Diabetes Association (research grant and mentored postdoctoral fellowship awards to M. E. P.), the Graetz Foundation (to M. E. P.), the Lilly Foundation (to M. E. P.), and the Lawson-Wilkins Pediatric Endocrine Society (to E. I.). This work was also supported in part by the Joslin DERC [5P30 DK036836-23]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 11 Z9 11 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 12 PY 2013 VL 8 IS 9 AR e72670 DI 10.1371/journal.pone.0072670 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242KO UT WOS:000326240100015 PM 24069155 ER PT J AU Xu, YX Ma, AN Liu, L AF Xu, Yu-Xin Ma, Anna Liu, Li TI Transforming Growth Factor beta Signaling Upregulates the Expression of Human GDP-Fucose Transporter by Activating Transcription Factor Sp1 SO PLOS ONE LA English DT Article ID NUCLEOTIDE-SUGAR TRANSPORTERS; RNA-POLYMERASE-II; TATA-BINDING-PROTEIN; ADHESION DEFICIENCY-II; TGF-BETA; GOLGI-APPARATUS; ENDOPLASMIC-RETICULUM; RECEPTOR ACTIVATION; MESSENGER-RNA; IN-VIVO AB GDP-fucose transporter plays a crucial role in fucosylation of glycoproteins by providing activated fucose donor, GDPfucose, for fucosyltransferases in the lumen of the Golgi apparatus. Fucose-containing glycans are involved in many biological processes, which are essential for growth and development. Mutations in the GDP-fucose transporter gene cause leukocyte adhesion deficiency syndrome II, a disease characterized by slow growth, mental retardation and immunodeficiency. However, no information is available regarding its transcriptional regulation. Here, by using human cells, we show that TGF-beta 1 specifically induces the GDP-fucose transporter expression, but not other transporters tested such as CMP-sialic acid transporter, suggesting a diversity of regulatory pathways for the expression of these transporters. The regulatory elements that are responsive to the TGF-beta 1 stimulation are present in the region between bp -330 and -268 in the GDP-fucose transporter promoter. We found that this region contains two identical octamer GC-rich motifs (GGGGCGTG) that were demonstrated to be essential for the transporter expression. We also show that the transcription factor Sp1 specifically binds to the GC-rich motifs in vitro and Sp1 coupled with phospho-Smad2 is associated with the promoter region covering the Sp1-beta inding motifs in vivo using chromatin immunoprecipitation (ChIP) assays. In addition, we further confirmed that Sp1 is essential for the GDP-fucose transporter expression stimulated by TGF-beta 1 using a luciferase reporter system. These results highlight the role of TGF-beta signaling in regulation of the GDP-fucose transporter expression via activating Sp1. This is the first transcriptional study for any nucleotide sugar transporters that have been identified so far. Notably, TGF-beta 1 receptor itself is known to be modified by fucosylation. Given the essential role of GDP-fucose transporter in fucosylation, the finding that TGF-beta 1 stimulates the expression of this transporter, suggests a possible intracellular link between the function of nucleotide sugar transporter and the TGF-beta signaling pathway. C1 [Xu, Yu-Xin; Ma, Anna; Liu, Li] Boston Univ, Goldman Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02215 USA. [Xu, Yu-Xin] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Xu, Yu-Xin] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Liu, L (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02215 USA. EM liul@bu.edu FU NIH [GM30365]; American Heart Association SDG [11SDG7670007] FX This research work was financially supported by NIH Grant R01 (GM30365) to Carlos B. Hirschberg and by American Heart Association SDG (11SDG7670007) to Yu-Xin Xu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 2 Z9 3 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 12 PY 2013 VL 8 IS 9 AR e74424 DI 10.1371/journal.pone.0074424 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242KO UT WOS:000326240100106 PM 24069312 ER PT J AU Nabel, EG Ferris, TG Slavin, PL AF Nabel, Elizabeth G. Ferris, Timothy G. Slavin, Peter L. TI Balancing AMCs' Missions and Health Care Costs - Mission Impossible? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material AB U.S. academic medical centers will soon feel pressure to control costs even as they balance the imperatives of clinical care with missions in research, teaching, and community health. Two large Massachusetts AMCs have begun addressing this challenge. When major provisions of the Affordable Care Act (ACA) are implemented next January, few institutions will feel the pressure to control costs more acutely than academic medical centers (AMCs), which must balance the imperatives of clinical care with cost-intensive missions in research, teaching, and community health. Massachusetts AMCs don't have to guess at the law's likely impact: in 2006, our state launched its own health care reform involving principles and policy solutions similar to the ACA's. Massachusetts therefore provides a laboratory for gauging the effects of such reforms. Having largely solved the insurance problem, Massachusetts passed sweeping cost-control legislation in ... C1 [Nabel, Elizabeth G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ferris, Timothy G.; Slavin, Peter L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nabel, Elizabeth G.; Ferris, Timothy G.; Slavin, Peter L.] Partners HealthCare, Boston, MA USA. RP Nabel, EG (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 3 TC 8 Z9 8 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 12 PY 2013 VL 369 IS 11 BP 994 EP 996 DI 10.1056/NEJMp1309179 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 216SK UT WOS:000324304200006 PM 24024836 ER PT J AU Finkelstein, JS Lee, H Burnett-Bowie, SAM Pallais, JC Yu, EW Borges, LF Jones, BF Barry, CV Wulczyn, KE Thomas, BJ Leder, BZ AF Finkelstein, Joel S. Lee, Hang Burnett-Bowie, Sherri-Ann M. Pallais, J. Carl Yu, Elaine W. Borges, Lawrence F. Jones, Brent F. Barry, Christopher V. Wulczyn, Kendra E. Thomas, Bijoy J. Leder, Benjamin Z. TI Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; BONE-MINERAL DENSITY; HEALTHY-YOUNG MEN; MUSCLE STRENGTH; SERUM TESTOSTERONE; HYPOGONADAL MEN; PROSTATE-CANCER; OLDER MEN; FAT DISTRIBUTION; ADIPOSE-TISSUE AB BackgroundCurrent approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both account for clinical manifestations. MethodsWe provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed. ResultsThe percentage of body fat increased in groups receiving placebo or 1.25 g or 2.5 g of testosterone daily without anastrozole (mean testosterone level, 4413 ng per deciliter, 19178 ng per deciliter, and 337173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25 g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced. ConclusionsThe amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function. Our findings support changes in the approach to evaluation and management of hypogonadism in men. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00114114.) C1 [Finkelstein, Joel S.; Burnett-Bowie, Sherri-Ann M.; Pallais, J. Carl; Yu, Elaine W.; Borges, Lawrence F.; Jones, Brent F.; Barry, Christopher V.; Wulczyn, Kendra E.; Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Thomas, Bijoy J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM jfinkelstein@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU National Institutes of Health FX Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00114114. NR 41 TC 184 Z9 187 U1 0 U2 27 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 12 PY 2013 VL 369 IS 11 BP 1011 EP 1022 DI 10.1056/NEJMoa1206168 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 216SK UT WOS:000324304200010 PM 24024838 ER PT J AU Brown, DFM Jaffer, FA Baker, JN Gurol, ME AF Brown, David F. M. Jaffer, Farouc A. Baker, Joshua N. Gurol, M. Edip TI Case 28-2013: A 52-Year-Old Man with Cardiac Arrest after an Acute Myocardial Infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID THERAPEUTIC HYPOTHERMIA; SURVIVAL; ASSOCIATION; ADULTS AB A 52-year-old man was brought to the emergency department with chest pain and ST-segment elevation. Seconds after his arrival, cardiac arrest occurred. CPR was begun, and nine external countershocks were administered, without resolution. Management decisions were made. Presentation of CaseDr. Lisa A. Arvold (Emergency Medicine): A 52-year-old man was brought to the emergency department at this hospital because of chest pain and ST-segment elevations on electrocardiography (ECG). The patient had been in his usual health, with hypertension, dyslipidemia, and coronary artery disease, until approximately 8:30 on the morning of admission, when his girlfriend found him lying on the floor of his home, unresponsive; she called emergency medical services (EMS). Shortly thereafter, he regained consciousness, rose to sit in a chair, and reported chest pain and dizziness. He took two nitroglycerin tablets (sublingually). On examination by EMS ... C1 [Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Baker, Joshua N.] Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. [Gurol, M. Edip] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Brown, David F. M.; Baker, Joshua N.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gurol, M. Edip] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RI Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU Boston Scientific FX Dr. Jaffer reports receiving consulting fees from Boston Scientific. No other potential conflict of interest relevant to this article was reported. NR 19 TC 6 Z9 7 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 12 PY 2013 VL 369 IS 11 BP 1047 EP 1054 DI 10.1056/NEJMcpc1304164 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 216SK UT WOS:000324304200014 PM 24024842 ER PT J AU Shanmugarajah, K Madariaga, ML Michel, S AF Shanmugarajah, Kumaran Madariaga, Maria Lucia Michel, Sebastian TI Nighttime Physician Staffing in an Intensive Care Unit Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Shanmugarajah, Kumaran] Imperial Coll London, London, England. [Madariaga, Maria Lucia] Massachusetts Gen Hosp Boston, Boston, MA USA. [Michel, Sebastian] Ludwig Maximilians Univ Munchen, Munich, Germany. RP Shanmugarajah, K (reprint author), Imperial Coll London, London, England. EM kshanmugarajah@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 12 PY 2013 VL 369 IS 11 BP 1075 EP 1075 DI 10.1056/NEJMc1308523 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 216SK UT WOS:000324304200037 PM 24024850 ER PT J AU Saber, W Cutler, CS Nakamura, R Zhang, MJ Atallah, E Rizzo, JD Maziarz, RT Cortes, J Kalaycio, ME Horowitz, MM AF Saber, Wael Cutler, Corey S. Nakamura, Ryotaro Zhang, Mei-Jie Atallah, Ehab Rizzo, J. Douglas Maziarz, Richard T. Cortes, Jorge Kalaycio, Matt E. Horowitz, Mary M. TI Impact of donor source on hematopoietic cell transplantation outcomes for patients with myelodysplastic syndromes (MDS) SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; MATCHED UNRELATED DONORS; HLA-IDENTICAL SIBLINGS; GRAFT-VERSUS-LEUKEMIA; RISK-STRATIFICATION; COMORBIDITY INDEX; DECISION-ANALYSIS; OLDER PATIENTS AB Allogeneic hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA) matched related donor (MRD) and matched unrelated donors (MUD) produces similar survival for patients with acute myelogenous leukemia. Whether these results can be extended to patients with myelodysplastic syndromes (MDS) is unknown. Therefore, analysis of post-HCT outcomes for MDS was performed. Outcomes of 701 adult MDS patients who underwent HCT between 2002 and 2006 were analyzed (MRD [n = 176], 8 of 8 HLA-A, -B, -C, -DRB1 allele matched MUD [n = 413], 7 of 8 MUD [n = 112]). Median age was 53 years (range, 22-78 years). In multivariate analyses, MRD HCT recipients had similar disease free survival (DFS) and survival rates compared with 8 of 8 MUD HCT recipients (relative risk [RR] 1.13 [95% confidence interval (CI) 0.91-1.42] and 1.24 [95% CI 0.98-1.56], respectively), and both MRD and 8 of 8 MUD had superior DFS (RR 1.47 [95% CI 1.10-1.96] and 1.29 [95% CI 1.00-1.66], respectively) and survival (RR 1.62 [95% CI 1.21-2.17] and 1.30 [95% CI 1.01-1.68], respectively) compared with 7 of 8 MUD HCT recipients. In patients with MDS, MRD remains the best stem cell source followed by 8 of 8 MUD. Transplantation from 7 of 8 MUD is associated with significantly poorer outcomes. C1 [Saber, Wael; Zhang, Mei-Jie; Rizzo, J. Douglas; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Atallah, Ehab] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kalaycio, Matt E.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. RP Saber, W (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM wsaber@mcw.edu FU National Institutes of Health, National Cancer Institute [U24-CA76518]; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases from National Heart, Lung and Blood Institute [5U01HL069294]; National Cancer Institute [HHSH234200637015C]; Health Resources and Services Administration; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix; GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture, Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle Genetics; Sigma-t Pharmaceuticals; Soligenix, Inc.; Swedish Orphan Biovitrum; THERAKOS, Inc.; Wellpoint, Inc. FX This work (CIBMTR) was supported by the Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Institutes of Health, National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases, a Grant/Cooperative Agreement 5U01HL069294 from the National Heart, Lung and Blood Institute and the National Cancer Institute, a contract HHSH234200637015C with Health Resources and Services Administration, 2 grants (N00014-06-1-0704 and N00014-08-1-0058) from the Office of Naval Research, and grants from Allos, Inc., Amgen, Inc., Angioblast, an anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association, Buchanan Family Foundation, CaridianBCT, Celgene Corporation, CellGenix, GmbH, Children's Leukemia Research Association, Fresenius-Biotech North America, Inc., Gamida Cell Teva Joint Venture, Ltd., Genentech, Inc., Genzyme Corporation, GlaxoSmithKline, Kiadis Pharma, The Leukemia & Lymphoma Society, The Medical College of Wisconsin, Millennium Pharmaceuticals, Inc., Milliman USA, Inc., Miltenyi Biotec, Inc., National Marrow Donor Program, Optum Healthcare Solutions, Inc., Otsuka America Pharmaceutical, Inc., Seattle Genetics, Sigma-t Pharmaceuticals, Soligenix, Inc., Swedish Orphan Biovitrum, THERAKOS, Inc., and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 49 TC 27 Z9 27 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 12 PY 2013 VL 122 IS 11 BP 1974 EP 1982 DI 10.1182/blood-2013-04-496778 PG 9 WC Hematology SC Hematology GA 220GN UT WOS:000324570900021 PM 23847196 ER PT J AU Ran, FA Hsu, PD Lin, CY Gootenberg, JS Konermann, S Trevino, AE Scott, DA Inoue, A Matoba, S Zhang, Y Zhang, F AF Ran, F. Ann Hsu, Patrick D. Lin, Chie-Yu Gootenberg, Jonathan S. Konermann, Silvana Trevino, Alexandro E. Scott, David A. Inoue, Azusa Matoba, Shogo Zhang, Yi Zhang, Feng TI Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity SO CELL LA English DT Article ID ZINC-FINGER NUCLEASES; TAL EFFECTORS; HUMAN-CELLS; BACTERIA; SYSTEM; TRANSCRIPTION; ENDONUCLEASE; GENERATION; MUTATIONS; KNOCKOUT AB Targeted genome editing technologies have enabled a broad range of research and medical applications. The Cas9 nuclease from the microbial CRISPR-Cas system is targeted to specific genomic loci by a 20 nt guide sequence, which can tolerate certain mismatches to the DNA target and thereby promote undesired off-target mutagenesis. Here, we describe an approach that combines a Cas9 nickase mutant with paired guide RNAs to introduce targeted double-strand breaks. Because individual nicks in the genome are repaired with high fidelity, simultaneous nicking via appropriately offset guide RNAs is required for double-stranded breaks and extends the number of specifically recognized bases for target cleavage. We demonstrate that using paired nicking can reduce off-target activity by 50- to 1,500-fold in cell lines and to facilitate gene knockout in mouse zygotes without sacrificing on-target cleavage efficiency. This versatile strategy enables a wide variety of genome editing applications that require high specificity. C1 [Ran, F. Ann; Hsu, Patrick D.; Lin, Chie-Yu; Gootenberg, Jonathan S.; Konermann, Silvana; Trevino, Alexandro E.; Scott, David A.; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Ran, F. Ann; Hsu, Patrick D.; Lin, Chie-Yu; Gootenberg, Jonathan S.; Konermann, Silvana; Scott, David A.; Zhang, Feng] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Ran, F. Ann; Hsu, Patrick D.; Lin, Chie-Yu; Gootenberg, Jonathan S.; Konermann, Silvana; Scott, David A.; Zhang, Feng] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ran, F. Ann; Hsu, Patrick D.; Lin, Chie-Yu; Gootenberg, Jonathan S.; Konermann, Silvana; Scott, David A.; Zhang, Feng] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Ran, F. Ann; Hsu, Patrick D.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Lin, Chie-Yu] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Inoue, Azusa; Matoba, Shogo; Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, F (reprint author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM zhang@broadinstitute.org RI Yang, Sheng/G-1606-2010 OI Yang, Sheng/0000-0003-3742-9989 FU National Institute of General Medical Sciences [T32GM007753]; NIH [GM68804, U01DK089565, 1DP1-MH100706, 1R01-DK097768] FX We thank Joshua Weinstein and Yinqing Li for statistical consultation, Xuebing Wu and Phillip Sharp for assistance with northern blotting experiments, Su Vora for help with the manuscript, and the entire Zhang lab for their support and advice. P.D.H. is a James Mills Pierce Fellow. C.-Y.L. is supported by T32GM007753 from the National Institute of General Medical Sciences. D.A.S. is an NSF predoctoral fellow. A.I. and S.M. are research fellows for Research Abroad of the Japan Society for the Promotion of Science. Y.Z. is supported by NIH grants GM68804 and U01DK089565 and is an Investigator of the Howard Hughes Medical Institute. F.Z. is supported by an NIH Director's Pioneer Award (1DP1-MH100706), a NIH Transformative R01 grant (1R01-DK097768), the Keck, McKnight, Damon Runyon, Searle Scholars, Klingen-stein, Vallee, and Simons Foundations, Bob Metcalfe, and Jane Pauley. NR 40 TC 765 Z9 838 U1 114 U2 682 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 12 PY 2013 VL 154 IS 6 BP 1380 EP 1389 DI 10.1016/j.cell.2013.08.021 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 215VQ UT WOS:000324239300024 PM 23992846 ER PT J AU Hemler, ME Hoff, J Li, Q Yang, XH AF Hemler, M. E. Hoff, J. Li, Q. Yang, X. H. TI Renal disease appears not to affect carcinogenesis in CD151-null mice SO ONCOGENE LA English DT Letter ID TETRASPANIN CD151; DELETION C1 [Hemler, M. E.; Li, Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hoff, J.; Yang, X. H.] Univ Kentucky, Albert B Chandler Med Ctr, Lexington, KY 40536 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Martin_Hemler@dfci.harvard.edu; xiuwei-yang@uky.edu RI Li, Qinglin/K-2570-2015 OI Li, Qinglin/0000-0002-4125-1944 NR 6 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 12 PY 2013 VL 32 IS 37 BP 4458 EP 4458 DI 10.1038/onc.2013.79 PG 1 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 218AF UT WOS:000324404200015 PM 23503459 ER PT J AU Bratcher, PE Gaggar, A AF Bratcher, Preston E. Gaggar, Amit TI Characterization and Prevention of the Adsorption of Surfactant Protein D to Polypropylene SO PLOS ONE LA English DT Article ID LUNG AB Surfactant Protein D (SP-D) is a multifunctional protein present in the lung and in respiratory secretions. In the process of developing new experimental approaches to examine SP-D function, we observed that SP-D adsorbs to polypropylene tubes to a great extent, thereby depleting SP-D from the solution. Although it is well known that proteins adsorb nonspecifically to plastic, this effect is usually diminished by treatments to make the plastic "low-retention" or "low-binding". However, these treatments actually increased the binding of SP-D to the plastic. In addition, this adsorption affected the results of several assays, including proteolytic cleavage assays. In order to block SP-D from adsorbing to polypropylene and the effects caused by this adsorption, we coated the tubes with bovine serum albumin (BSA), as is commonly performed for ELISAs. This coating greatly diminished the amount of SP-D sticking to the plastic, providing an inexpensive and effective method for preventing adsorption and the artifacts resulting from this adsorption. C1 [Bratcher, Preston E.; Gaggar, Amit] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, Lung Hlth Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] Med Serv, US Dept Vet Affairs, Med Ctr, Birmingham, AL USA. RP Bratcher, PE (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. EM bratcher@uab.edu FU National Institutes of Health [HL102371, 5T32HL105346-02]; Cystic Fibrosis Foundation [GAGGAR07] FX This work is supported by the National Institutes of Health (HL102371 to AG, 5T32HL105346-02 to PEB) and the Cystic Fibrosis Foundation (GAGGAR07 to AG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 11 TC 5 Z9 5 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 11 PY 2013 VL 8 IS 9 AR e73467 DI 10.1371/journal.pone.0073467 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 248VW UT WOS:000326734500034 PM 24039953 ER PT J AU Ma, YX Wang, SX Tian, YH Chen, L Li, GY Mao, JR AF Ma, Yuxin Wang, Shuxing Tian, Yinghong Chen, Lucy Li, Guoying Mao, Jianren TI Disruption of Persistent Nociceptive Behavior in Rats with Learning Impairment SO PLOS ONE LA English DT Article ID LONG-TERM POTENTIATION; ASPARTATE RECEPTOR ANTAGONIST; NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; COGNITIVELY INTACT; PROTEIN-SYNTHESIS; SELECTIVE IMPAIRMENT; SYNAPTIC PLASTICITY; GLUTAMATE UPTAKE; MEMORY DEFICITS AB Despite the subjective nature of pain experience with cognitive and affective dimensions, preclinical pain research has largely focused on its sensory dimension. Here, we examined the relationship between learning/memory and nociceptive behavior in rats with combined learning impairment and persistent nociception. Learning impairment was induced by bilateral hippocampal injection of a mixed A beta solution, whereas persistent nociception produced in these rats by complete Freund's adjuvant-induced ankle inflammation. Those rats with learning impairment showed a diminished development of thermal hyperalgesia and mechanical allodynia and a shorter time course of nociceptive behavior without alteration of their baseline nociceptive threshold. In rats with pre-established hyperalgesia and allodynia due to ankle inflammation, bilateral intra-hippocampal injection of cycloheximide (a protein synthesis inhibitor) promoted the earlier recovery of nociceptive behavior. Moreover, expression of A beta, NR1 subunit of the N-methyl-D-aspartate receptor, and protein kinase C gamma was upregulated, whereas the choline acetyl transferase expression was downregulated, in the hippocampus, thalamus, amygdala, and/or spinal cord of rats with combined learning impairment and persistent nociception. The data indicate that learning impairment could disrupt the response to a state of persistent nociception, suggesting an important role for cognitive maladaptation in the mechanisms of chronic pain. These results also suggest that a preclinical model of combined learning impairment and persistent nociception may be useful to explore the brain mechanisms underlying the transition from acute to chronic pain. C1 [Ma, Yuxin; Wang, Shuxing; Tian, Yinghong; Chen, Lucy; Mao, Jianren] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med,MGH Ctr Tran, Boston, MA 02115 USA. [Ma, Yuxin; Li, Guoying] Guangdong Pharmaceut Univ, Sch Basic Med, Dept Anat, Guangzhou, Guangdong, Peoples R China. [Ma, Yuxin] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Anat, Guangzhou 510275, Guangdong, Peoples R China. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med,MGH Ctr Tran, Boston, MA 02115 USA. EM jmao@partners.org FU NIH [R01 DE022901, P20 DA26002, R01 DE18538] FX This study was supported by NIH grants R01 DE022901, P20 DA26002 and R01 DE18538. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 3 Z9 3 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 11 PY 2013 VL 8 IS 9 AR UNSP e74533 DI 10.1371/journal.pone.0074533 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 248VW UT WOS:000326734500100 PM 24040273 ER PT J AU Xu, Y Lopes, C Wende, H Guo, Z Cheng, LP Birchmeier, C Ma, QF AF Xu, Yi Lopes, Claudia Wende, Hagen Guo, Zhen Cheng, Leping Birchmeier, Carmen Ma, Qiufu TI Ontogeny of Excitatory Spinal Neurons Processing Distinct Somatic Sensory Modalities SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CORD DORSAL-HORN; AFFERENT-FIBERS; INTERNEURONS; PAIN; RECEPTOR; ITCH; SPECIFICATION; TLX3; LBX1; MICE AB Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dIL(A), and dIL(B) subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dIL(B) cells. In these CKO mice, development of a subset of excitatory neurons located in laminae I and II was impaired, including itch-related GRPR-expressing neurons, PKC gamma-expressing neurons, and neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1, and the gastrin-releasing peptide. These CKO mice displayed marked deficits in generating nocifensive motor behaviors evoked by a range of pain-related or itch-related stimuli. The mutants also failed to exhibit escape response evoked by dynamic mechanical stimuli but retained the ability to sense innocuous cooling and/or warm. Thus, our studies provide new insight into the ontogeny of spinal neurons processing distinct sensory modalities. C1 [Xu, Yi; Lopes, Claudia; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Xu, Yi; Lopes, Claudia; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Wende, Hagen; Birchmeier, Carmen] Max Delbruck Ctr, Dept Neurosci, D-13125 Berlin, Germany. [Guo, Zhen; Cheng, Leping] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM Qiufu_Ma@dfci.harvard.edu FU National Institutes of Health, National Institute of Neurological Disorders and Stroke [R01NS047710] FX The work done in the Q.M. laboratory was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke Grant R01NS047710. We thank Dr. Silvia Arber for the Tau-loxp-STOP-lox-mGFP-IRES-NLS-LacZ reporter mice; Dr. Jean-Francois Brunet for the Phox2a antibody; and Drs. Clifford Woolf, Wendy Knowlton, Fu-Chia Yang, and Bo Duan for critical discussions and comments. NR 52 TC 22 Z9 22 U1 0 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 11 PY 2013 VL 33 IS 37 BP 14738 EP 14748 DI 10.1523/JNEUROSCI.5512-12.2013 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 216WG UT WOS:000324316200012 PM 24027274 ER PT J AU Reed, M Huang, J Brand, R Graetz, I Neugebauer, R Fireman, B Jaffe, M Ballard, DW Hsu, J AF Reed, Mary Huang, Jie Brand, Richard Graetz, Ilana Neugebauer, Romain Fireman, Bruce Jaffe, Marc Ballard, Dustin W. Hsu, John TI Implementation of an Outpatient Electronic Health Record and Emergency Department Visits, Hospitalizations, and Office Visits Among Patients With Diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INFORMATION-TECHNOLOGY; AMBULATORY-CARE; MEDICAL-RECORD; QUALITY; SYSTEMS; IMPACT; PHYSICIANS; BENEFITS; OUTCOMES; COSTS AB IMPORTANCE The US federal government is spending billions of dollars in physician incentives to encourage the meaningful use of electronic health records (EHRs). Although the use of EHRs has potential to improve patient health outcomes, the existing evidence has been limited and inconsistent. OBJECTIVE To examine the association between implementing a commercially available outpatient EHR and emergency department (ED) visits, hospitalizations, and office visits for patients with diabetes mellitus. DESIGN, SETTING, AND POPULATION Staggered EHR implementation across outpatient clinics in an integrated delivery system (Kaiser Permanente Northern California) between 2005 and 2008 created an opportunity for studying changes associated with EHR use. Among a population-based sample of 169 711 patients with diabetes between 2004 and 2009, we analyzed 4 997 585 person-months before EHR implementation and 4 648 572 person-months after an EHR was being used by patients' physicians. MAIN OUTCOMES AND MEASURES We examined the association between EHR use and unfavorable clinical events (ED visits and hospitalizations) and office visit use among patients with diabetes, using multivariable regression with patient-level fixed-effect analyses and adjustment for trends over time. RESULTS In multivariable analyses, use of the EHR was associated with a statistically significantly decreased number of ED visits, 28.80 fewer visits per 1000 patients annually (95% CI, 20.28 to 37.32), from a mean of 519.12 visits per 1000 patients annually without using the EHR to 490.32 per 1000 patients when using the EHR. The EHR was also associated with 13.10 fewer hospitalizations per 1000 patients annually (95% CI, 7.37 to 18.82), from a mean of 251.60 hospitalizations per 1000 patients annually with no EHR to 238.50 per 1000 patients annually when using the EHR. There were similar statistically significant reductions in nonelective hospitalizations (10.92 fewer per 1000 patients annually) and hospitalizations for ambulatory care-sensitive conditions (7.08 fewer per 1000 patients annually). There was no statistically significant association between EHR use and office visit rates. CONCLUSIONS AND RELEVANCE Among patients with diabetes, use of an outpatient EHR in an integrated delivery system was associated with modest reductions in ED visits and hospitalizations but not office visit rates. Further studies are needed to quantify the association of EHR use with changes in costs. C1 [Reed, Mary; Huang, Jie; Graetz, Ilana; Neugebauer, Romain; Fireman, Bruce] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Brand, Richard] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Jaffe, Marc] Permanente Med Grp Inc, Dept Med & Endocrinol, San Francisco, CA USA. [Ballard, Dustin W.] Permanente Med Grp Inc, Dept Emergency Med, San Rafael, CA USA. [Hsu, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Reed, M (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94610 USA. EM mary.e.reed@kp.org RI Graetz, Ilana/N-1189-2016 OI Graetz, Ilana/0000-0003-3664-5815 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01DK085070]; Agency for Healthcare Research and Quality [R01HS015280] FX Research reported herein was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award R01DK085070 and the Agency for Healthcare Research and Quality under award R01HS015280. NR 27 TC 26 Z9 27 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 11 PY 2013 VL 310 IS 10 BP 1060 EP 1065 DI 10.1001/jama.2013.276733 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 214KZ UT WOS:000324133400023 PM 24026601 ER PT J AU Venkatasubbarao, K Peterson, L Zhao, SJ Hill, P Cao, L Zhou, Q Nawrocki, ST Freeman, JW AF Venkatasubbarao, Kolaparthi Peterson, Lindsay Zhao, Shujie Hill, Ping Cao, Lin Zhou, Qing Nawrocki, Steffan T. Freeman, James W. TI Inhibiting signal transducer and activator of transcription-3 increases response to gemcitabine and delays progression of pancreatic cancer SO MOLECULAR CANCER LA English DT Article DE Pancreatic cancer; STAT3; EGFR inhibitor; Cancer therapy ID GROWTH-FACTOR RECEPTOR; CELL-LINE; STAT3; CARCINOMA; APOPTOSIS; SURVIVAL; THERAPY; PATHWAY; ADENOCARCINOMA; CHEMOTHERAPY AB Background: Among the solid tumors, human pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis. Gemcitabine is the standard first line of therapy for pancreatic cancer but has limited efficacy due to inherent or rapid development of resistance and combining EGFR inhibitors with this regimen results in only a modest clinical benefit. The goal of this study was to identify molecular targets that are activated during gemcitabine therapy alone or in combination with an EGFR inhibitor. Methods: PDAC cell lines were used to determine molecular changes and rates of growth after treatment with gemcitabine or an EGFR inhibitor, AG1478, by Western blot analysis and MTT assays respectively. Flow cytometric analysis was performed to study the cell cycle progression and rate of apoptosis after gemcitabine treatment. ShRNA was used to knockdown STAT3. An in vivo orthotopic animal model was used to evaluate STAT3 as a target. Immunohistochemical analysis was performed to analyze Ki67 and STAT3 expression in tumors. Results: Treatment with gemcitabine increased the levels of EGFR(Tyr1068) and ERK phosphorylation in the PDAC cell lines tested. The constitutive STAT3(Tyr705) phosphorylation observed in PDAC cell lines was not altered by treatment with gemcitabine. Treatment of cells with gemcitabine or AG1478 resulted in differential rate of growth inhibition. AG1478 efficiently blocked the phosphorylation of EGFR(Tyr1068) and inhibited the phosphorylation of down-stream effectors AKT and ERKs, while STAT3(Tyr705) phosphorylation remained unchanged. Combining these two agents neither induced synergistic growth suppression nor inhibited STAT3(Tyr705) phosphorylation, thus prompting further studies to assess whether targeting STAT3 improves the response to gemcitabine or AG1478. Indeed, knockdown of STAT3 increased sensitivity to gemcitabine by inducing pro-apoptotic signals and by increasing G1 cell cycle arrest. However, knockdown of STAT3 did not enhance the growth inhibitory potential of AG1478. In vivo orthotopic animal model results show that knockdown of STAT3 caused a significant reduction in tumor burden and delayed tumor progression with increased response to gemcitabine associated with a decrease in the Ki-67 positive cells. Conclusions: This study suggests that STAT3 should be considered an important molecular target for therapy of PDAC for enhancing the response to gemcitabine. C1 [Venkatasubbarao, Kolaparthi; Peterson, Lindsay; Zhao, Shujie; Hill, Ping; Cao, Lin; Zhou, Qing; Nawrocki, Steffan T.; Freeman, James W.] Univ Texas San Antonio, Hlth Sci Ctr, Div Hematol & Oncol, Dept Med, San Antonio, TX 78229 USA. [Venkatasubbarao, Kolaparthi; Peterson, Lindsay; Zhao, Shujie; Hill, Ping; Cao, Lin; Zhou, Qing; Nawrocki, Steffan T.; Freeman, James W.] Canc Therapy & Res Ctr S Texas, Expt & Dev Therapeut Program, San Antonio, TX 78229 USA. [Freeman, James W.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Freeman, JW (reprint author), Univ Texas San Antonio, Hlth Sci Ctr, Div Hematol & Oncol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM FREEMANJW@UTHSCSA.EDU FU NIH/NCI [RO1 CA69122]; VA-Merit Award; Cancer Center Grant NIH/NCI [P30CA054174] FX This study was supported by NIH/NCI grant RO1 CA69122 and VA-Merit Award to JWF and Cancer Center Grant NIH/NCI P30CA054174 in support of the UTHSCSA Core Flow Cytometry Facility. The authors would like to thank Dr. Subrata Haldar and Ms. Susan Beardales, Division of Scientific Writing, CTRC, UTHSCSA for helpful suggestions during the preparation of this manuscript. NR 34 TC 12 Z9 13 U1 0 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD SEP 11 PY 2013 VL 12 AR 104 DI 10.1186/1476-4598-12-104 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 220BE UT WOS:000324554900001 PM 24025152 ER PT J AU Gazit, R Garrison, BS Rao, TN Shay, T Costello, J Ericson, J Kim, F Collins, JJ Regev, A Wagers, AJ Rossi, DJ AF Gazit, Roi Garrison, Brian S. Rao, Tata Nageswara Shay, Tal Costello, James Ericson, Jeff Kim, Francis Collins, James J. Regev, Aviv Wagers, Amy J. Rossi, Derrick J. CA Immunological Genome Project Conso TI Transcriptome Analysis Identifies Regulators of Hematopoietic Stem and Progenitor Cells SO STEM CELL REPORTS LA English DT Article ID COLONY-STIMULATING FACTOR; GENE-EXPRESSION; SELF-RENEWAL; BLOOD; QUIESCENCE; MOBILIZATION; MIGRATION; LEUKEMIA; MARROW; FAMILY AB Hematopoietic stem cells (HSCs) maintain blood homeostasis and are the functional units of bone marrow transplantation. To improve the molecular understanding of HSCs and their proximal progenitors, we performed transcriptome analysis within the context of the ImmGen Consortium data set. Gene sets that define steady-state and mobilized HSCs, as well as hematopoietic stem and progenitor cells (HSPCs), were determined. Genes involved in transcriptional regulation, including a group of putative transcriptional repressors, were identified in multipotent progenitors and HSCs. Proximal promoter analyses combined with ImmGen module analysis identified candidate regulators of HSCs. Enforced expression of one predicted regulator, Hlf, in diverse HSPC subsets led to extensive self-renewal activity ex vivo. These analyses reveal unique insights into the mechanisms that control the core properties of HSPCs. C1 [Gazit, Roi; Garrison, Brian S.; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Gazit, Roi; Garrison, Brian S.; Rao, Tata Nageswara; Kim, Francis; Wagers, Amy J.; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Rao, Tata Nageswara; Kim, Francis; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Shay, Tal; Regev, Aviv] Broad Inst, Cambridge, MA 02142 USA. [Costello, James; Collins, James J.] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA. [Ericson, Jeff] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Collins, James J.; Regev, Aviv; Wagers, Amy J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Gazit, Roi] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol Immunol & Genet, IL-84105 Beer Sheva, Israel. RP Rossi, DJ (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM derrick.rossi@childrens.harvard.edu RI Shay, Tal/J-4028-2016; OI Shay, Tal/0000-0003-0755-1350; Gazit, Roi/0000-0002-0548-2147 FU NIH/NIAID [R24 AI072073]; GlaxoSmithKline; J.C.F. fellowship; [R01 HL088582]; [R01 HL107630] FX We thank Christophe Benoist and Christoph Bock for insights, and Girijesh Buruzula and Joyce LaVecchio for technical assistance. This work was supported by R24 AI072073 from NIH/NIAID to the ImmGen Consortium, R01 HL088582 to A.J.W., R01 HL107630 to D.J.R., and research funds provided by GlaxoSmithKline. R.G. was supported by a J.C.F. fellowship. A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. D.J.R. is a New York Stem Cell Foundation Robertson Investigator. NR 49 TC 31 Z9 31 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD SEP 10 PY 2013 VL 1 IS 3 BP 266 EP 280 DI 10.1016/j.stemcr.2013.07.004 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1SO UT WOS:000336632700006 PM 24319662 ER PT J AU Bardia, A Juric, D Isakoff, SJ Borger, DR Dias-Santagata, D Higgins, MJ Iafrate, AJ Flaherty, K Moy, B Ellisen, LW AF Bardia, Aditya Juric, Dejan Isakoff, Steven J. Borger, Darrell R. Dias-Santagata, Dora Higgins, Michaela Jane Iafrate, Anthony John Flaherty, Keith Moy, Beverly Ellisen, Leif William TI Impact of routine tumor genotyping on enrollment in targeted therapy trials for metastatic breast cancer (MBC): 4-year review. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Breast Cancer Symposium CY SEP 07-09, 2013 CL San Francisco, CA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2013 VL 31 IS 26 SU S MA 145 PG 1 WC Oncology SC Oncology GA AG6YJ UT WOS:000335564700116 ER PT J AU Iyengar, NM Morris, PG Patil, S Chen, C Abbruzzi, A Lehman, RJ Steingart, R Oeffinger, KC Lin, NU Moy, B Come, SE Winer, EP Norton, L Hudis, C Dang, CT AF Iyengar, Neil M. Morris, Patrick Glyn Patil, Sujata Chen, Carol Abbruzzi, Alyson Lehman, Robert James Steingart, Richard Oeffinger, Kevin C. Lin, Nancy U. Moy, Beverly Come, Steven E. Winer, Eric P. Norton, Larry Hudis, Clifford Dang, Chau T. TI Longer-term cardiac safety and outcomes of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Breast Cancer Symposium CY SEP 07-09, 2013 CL San Francisco, CA C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2013 VL 31 IS 26 SU S MA 167 PG 1 WC Oncology SC Oncology GA AG6YJ UT WOS:000335564700137 ER PT J AU Peterson, DJ Truong, P Sadek, B Shenouda, M Taghian, A Alexander, C AF Peterson, David John Truong, Pauline Sadek, Betro Shenouda, Mina Taghian, Alphonse Alexander, Cheryl TI Do locoregional recurrence and survival outcomes differ in women with node-negative, HER2-positive breast cancer treated with breast-conserving therapy versus mastectomy? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Breast Cancer Symposium CY SEP 07-09, 2013 CL San Francisco, CA C1 British Columbia Canc Agcy, Victoria, BC, Canada. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2013 VL 31 IS 26 SU S MA 69 PG 1 WC Oncology SC Oncology GA AG6YJ UT WOS:000335564700044 ER PT J AU Reynolds, KL Cheng, XX Bhatia, A Specht, MC Smith, BL Moy, B Bardia, A AF Reynolds, Kerry Lynn Cheng, XingXing Bhatia, Ashmeet Specht, Michelle Connolly Smith, Barbara Lynn Moy, Beverly Bardia, Aditya TI Neoadjuvant single and dual HER2 blockade among patients with localized HER2-positive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Breast Cancer Symposium CY SEP 07-09, 2013 CL San Francisco, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. North Shore Med Ctr, Salem, MA USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2013 VL 31 IS 26 SU S MA 147 PG 1 WC Oncology SC Oncology GA AG6YJ UT WOS:000335564700117 ER PT J AU Yardley, DA Krop, IE LoRusso, P Robert, NJ Mayer, M Abidoye, OO Lai, C Yoo, B Perez, EA AF Yardley, Denise Aysel Krop, Ian E. LoRusso, Patricia Robert, Nicholas J. Mayer, Musa Abidoye, Oyewale O. Lai, Catherine Yoo, Bongin Perez, Edith A. TI Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Breast Cancer Symposium CY SEP 07-09, 2013 CL San Francisco, CA C1 Sarah Cannon Res Inst, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Karmanos Canc Inst, Detroit, MI USA. Virginia Canc Specialists, US Oncol Res Network, Fairfax, VA USA. AdvancedBC Org, New York, NY USA. Genentech Inc, San Francisco, CA 94080 USA. Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2013 VL 31 IS 26 SU S MA 166 PG 1 WC Oncology SC Oncology GA AG6YJ UT WOS:000335564700136 ER PT J AU Beaudoin, J Levine, RA Guerrero, JL Yosefy, C Sullivan, S Abedat, S Handschumacher, MD Szymanski, C Gilon, D Palmeri, NO Vlahakes, GJ Hajjar, RJ Beeri, R AF Beaudoin, Jonathan Levine, Robert A. Guerrero, J. Luis Yosefy, Chaim Sullivan, Suzanne Abedat, Susan Handschumacher, Mark D. Szymanski, Catherine Gilon, Dan Palmeri, Nicholas O. Vlahakes, Gus J. Hajjar, Roger J. Beeri, Ronen TI Late Repair of Ischemic Mitral Regurgitation Does Not Prevent Left Ventricular Remodeling Importance of Timing for Beneficial Repair SO CIRCULATION LA English DT Article; Proceedings Paper CT Scientific Sessions of the American-Heart-Association (AHA) CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE heart disease; ischemic; mitral valve regurgitation; remodeling ID MYOCARDIAL-INFARCTION; VALVE ANNULOPLASTY; PAPILLARY-MUSCLE; VOLUME OVERLOAD; WALL COMPLEX; IN-VIVO; LEAFLET; GEOMETRY; MECHANISM; HEART AB Background-Ischemic mitral regurgitation (MR) is a frequent complication of myocardial infarction associated with left ventricular (LV) dilatation and dysfunction, which doubles mortality. At the molecular level, moderate ischemic MR is characterized by a biphasic response, with initial compensatory rise in prohypertrophic and antiapoptotic signals, followed by their exhaustion. We have shown that early MR repair 30 days after myocardial infarction is associated with LV reverse remodeling. It is not known whether MR repair performed after the exhaustion of compensatory mechanisms is also beneficial. We hypothesized that late repair will not result in LV reverse remodeling. Methods and Results-Twelve sheep underwent distal left anterior descending coronary artery ligation to create apical myocardial infarction and implantation of an LV-to-left atrium shunt to create standardized moderate volume overload. At 90 days, animals were randomized to shunt closure (late repair) versus sham (no repair). LV remodeling was assessed by 3-dimensional echocardiography, dP/dt, preload-recruitable stroke work, and myocardial biopsies. At 90 days, animals had moderate volume overload, LV dilatation, and reduced ejection fraction (all P< 0.01 versus baseline, P=NS between groups). Shunt closure at 90 days corrected the volume overload (regurgitant fraction 6 +/- 5% versus 27 +/- 16% for late repair versus sham, P<0.01) but was not associated with changes in LV volumes (end-diastolic volume 106 +/- 15 versus 110 +/- 22 mL; end-systolic volume 35 +/- 6 versus 36 +/- 6 mL) or increases in preload-recruitable stroke work (41 +/- 7 versus 39 +/- 13 mL mm Hg) or dP/dt (803 +/- 210 versus 732 +/- 194 mm Hg/s) at 135 days (all P=NS). Activated Akt, central in the hypertrophic process, and signal transducer and activator of transcription 3 (STAT3), a critical node in the hypertrophic stimulus by cytokines, were equally depressed in both groups. Conclusions-Late correction of moderate volume overload after myocardial infarction did not improve LV volume or contractility. Upregulation of prohypertrophic intracellular pathways was not observed. This contrasts with previously reported study in which early repair (30 days) reversed LV remodeling. This suggests a window of opportunity to repair ischemic MR after which no beneficial effect on LV is observed, despite successful repair. C1 [Beaudoin, Jonathan; Levine, Robert A.; Guerrero, J. Luis; Yosefy, Chaim; Sullivan, Suzanne; Handschumacher, Mark D.; Szymanski, Catherine; Palmeri, Nicholas O.; Vlahakes, Gus J.; Beeri, Ronen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Abedat, Susan; Gilon, Dan; Beeri, Ronen] Hadassah Hebrew Univ, Med Ctr, Cardiovasc Res Ctr, Inst Heart, IL-91120 Jerusalem, Israel. [Hajjar, Roger J.] Mt Sinai Sch Med, Cardiovasc Res Ctr, Cardiovasc Inst, New York, NY USA. RP Beeri, R (reprint author), Hadassah Hebrew Univ, Med Ctr, Cardiovasc Res Ctr, Inst Heart, POB 12000, IL-91120 Jerusalem, Israel. EM RBEERI@partners.org RI Beeri, Ronen/A-4035-2009 OI Beeri, Ronen/0000-0002-8014-0702 FU NCATS NIH HHS [8UL1TR000170-05, UL1 TR000170]; NHLBI NIH HHS [R01 HL072265, R01 HL109506, R01 HL72265, HL109506, K24 HL67434, K24 HL067434, R01 HL119046] NR 25 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 10 PY 2013 VL 128 IS 11 SU 1 BP S248 EP S252 DI 10.1161/CIRCULATIONAHA.112.000124 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 301MD UT WOS:000330535500032 PM 24030415 ER PT J AU Bossone, E Corteville, DC Harris, KM Suzuki, T Fattori, R Hutchison, S Ehrlich, MP Pyeritz, RE Steg, PG Greason, K Evangelista, A Kline-Rogers, E Montgomery, DG Isselbacher, EM Nienaber, CA Eagle, KA AF Bossone, Eduardo Corteville, David C. Harris, Kevin M. Suzuki, Toru Fattori, Rossella Hutchison, Stuart Ehrlich, Marek P. Pyeritz, Reed E. Steg, Philippe Gabriel Greason, Kevin Evangelista, Arturo Kline-Rogers, Eva Montgomery, Daniel G. Isselbacher, Eric M. Nienaber, Christoph A. Eagle, Kim A. TI Stroke and Outcomes in Patients With Acute Type A Aortic Dissection SO CIRCULATION LA English DT Article; Proceedings Paper CT Scientific Sessions of the American-Heart-Association (AHA) CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE aortic dissection; mortality; stroke management ID ACUTE ISCHEMIC-STROKE; NEUROLOGICAL COMPLICATIONS; CEREBRAL INFARCTION; SYMPTOMS; REPAIR; COMA AB Background-Stroke is a highly dreaded complication of type A acute aortic dissection (TAAAD). However, little data exist on its incidence and association with prognosis. Methods and Results-We evaluated 2202 patients with TAAAD (mean age 62 +/- 14 years, 1487 [67.5%] men) from the International Registry of Acute Aortic Dissection to determine the incidence and prognostic impact of stroke in TAAAD. Stroke was present at arrival in 132 (6.0%) patients with TAAAD. These patients were older (65 +/- 12 versus 62 +/- 15 years; P=0.002) and more likely to have hypertension (86% versus 71%; P=0.001) or atherosclerosis (29% versus 22%; P=0.04) than patients without stroke. Chest pain at arrival was less common in patients with stroke (70% versus 82%; P<0.001), and patients with stroke presented more often with syncope (44% versus 15%; P<0.001), shock (14% versus 7%; P=0.005), or pulse deficit (51% versus 29%; P=0.001). Arch vessel involvement was more frequent among patients with stroke (68% versus 37%; P<0.001). They had less surgical management (74% versus 85%; P<0.001). Hospital stay was significantly longer in patients with stroke (median 17.9 versus 13.3 days; P<0.001). In-hospital complications, such as hypotension, coma, and malperfusion syndromes, and in-hospital mortality (adjusted odds ratio, 1.62; 95% confidence interval, 0.99-2.65) were higher among patients with stroke. Among hospital survivors, follow-up mortality was similar between groups (adjusted hazard ratio, 1.15; 95% confidence interval, 0.46-2.89). Conclusions-Stroke occurred in >1 of 20 patients with TAAAD and was associated with increased in-hospital morbidity but not long-term mortality. Whether aggressive early invasive interventions will reduce negative outcomes remains to be evaluated in future studies. C1 [Bossone, Eduardo] Univ Salerno, Dept Cardiol, I-84100 Salerno, Italy. [Corteville, David C.; Kline-Rogers, Eva; Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Harris, Kevin M.] Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN 55407 USA. [Suzuki, Toru] Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan. [Fattori, Rossella] San Salvatore Hosp, Dept Intervent Cardiol, Pesaro, Italy. [Hutchison, Stuart] Univ Calgary, Dept Cardiac Sci, Calgary, AB, Canada. [Ehrlich, Marek P.] Univ Vienna, Dept Cardiothorac Surg, Vienna, Austria. [Pyeritz, Reed E.] Univ Penn, Div Med Genet, Philadelphia, PA 19104 USA. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, Dept Cardiol, F-75877 Paris, France. [Greason, Kevin] Mayo Clin, Div Cardiovasc Surg, Rochester, MN USA. [Evangelista, Arturo] Hosp Gen Univ Vall dHebron, Serv Cardiol, Barcelona, Spain. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Rostock, Dept Internal Med, D-18055 Rostock, Germany. RP Bossone, E (reprint author), Univ Salerno, Div Cardiol, Cava de Tirreni & Amalfi Coast Hosp, Heart Dept, Via Pr Amedeo 36, I-84100 Salerno, Italy. EM ebossone@hotmail.com NR 25 TC 21 Z9 21 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 10 PY 2013 VL 128 IS 11 SU 1 BP S175 EP S179 DI 10.1161/CIRCULATIONAHA.112.000327 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 301MD UT WOS:000330535500021 PM 24030403 ER PT J AU Eckhouse, SR Logdon, CB Oelsen, JM Patel, RK Rice, AD Stroud, RE Wince, WB Mukherjee, R Spinale, FG Ikonomidis, JS Jones, JA AF Eckhouse, Shaina R. Logdon, Christina B. Oelsen, J. Marshall Patel, Risha K. Rice, Allison D. Stroud, Robert E. Wince, W. Benjamin Mukherjee, Rupak Spinale, Francis G. Ikonomidis, John S. Jones, Jeffrey A. TI Reproducible Porcine Model of Thoracic Aortic Aneurysm SO CIRCULATION LA English DT Article; Proceedings Paper CT Scientific Sessions of the American-Heart-Association (AHA) CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE animal models; aortic diseases; aneurysm; cardiovascular disease; remodeling ID MATRIX METALLOPROTEINASES; MURINE MODEL; TISSUE INHIBITORS; ABDOMINAL-AORTA; VALVES; EXPRESSION; DISSECTIONS; INDUCTION; INFUSION; DISEASE AB Background-Thoracic aortic aneurysms (TAAs) develop secondary to abnormal aortic extracellular matrix remodeling, resulting in a weakened and dilated aortic wall that progressed to rupture if left unattended. Currently, no diagnostic/prognostic tests are available for the detection of TAA disease. This is largely driven by the lack of a large animal model, which would permit longitudinal/mechanistic studies. Accordingly, the objective of the present study was to establish a reproducible porcine model of aortic dilatation, which recapitulates the structural and biochemical changes observed during human TAA development. Methods and Results-Descending TAAs were induced in Yorkshire pigs (20-25 kg; n=7) through intra-adventitial injections of collagenase (5 mL, 0.35 mg/mL) and periadventitial application of crystalline CaCl2 (0.5 g). Three weeks after TAA induction, aortas were harvested and tissue was collected for biochemical and histological measurements. A subset of animals underwent MRI preoperatively and at terminal surgery. Results were compared with sham-operated controls (n=6). Three weeks after TAA induction, aortic luminal area increased by 38 +/- 13% (P=0.018 versus control). Aortic structural changes included elastic lamellar degradation and decreased collagen content. The protein abundance of matrix metalloproteinases 3, 8, 9, and 12 increased in TAA tissue homogenates, whereas tissue inhibitors of metalloproteinases 1 and 4 decreased. Conclusions-These data demonstrate aortic dilatation, aortic medial degeneration, and alterations in matrix metalloproteinase/tissue inhibitors of metalloproteinase abundance, consistent with TAA formation. This study establishes for the first time a large animal model of TAA that recapitulates the hallmarks of human disease and provides a reproducible test bed for examining diagnostic, prognostic, and therapeutic strategies. C1 [Eckhouse, Shaina R.; Logdon, Christina B.; Oelsen, J. Marshall; Patel, Risha K.; Rice, Allison D.; Stroud, Robert E.; Mukherjee, Rupak; Ikonomidis, John S.; Jones, Jeffrey A.] Med Univ S Carolina, Div Cardiothorac Surg, Dept Surg, Charleston, SC 29425 USA. [Wince, W. Benjamin] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Jones, Jeffrey A.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Spinale, Francis G.] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC USA. [Spinale, Francis G.] Wm Jennings Bryan Dorn Vet Affairs Med Ctr, Columbia, SC USA. RP Jones, JA (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Strom Thurmond Res Bldg,114 Doughty St,Suite 326C, Charleston, SC 29425 USA. EM jonesja@musc.edu FU NHLBI NIH HHS [T32 HL007260] NR 39 TC 4 Z9 4 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 10 PY 2013 VL 128 IS 11 SU 1 BP S186 EP S193 DI 10.1161/CIRCULATIONAHA.112.000363 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 301MD UT WOS:000330535500023 PM 24030405 ER PT J AU Teman, NR Peterson, MD Russo, MJ Ehrlich, MP Myrmel, T Upchurch, GR Greason, K Fillinger, M Forteza, A Deeb, GM Montgomery, DG Eagle, KA Isselbacher, EM Nienaber, CA Patel, HJ AF Teman, Nicholas R. Peterson, Mark D. Russo, Mark J. Ehrlich, Marek P. Myrmel, Truls Upchurch, Gilbert R., Jr. Greason, Kevin Fillinger, Mark Forteza, Alberto Deeb, George Michael Montgomery, Daniel G. Eagle, Kim A. Isselbacher, Eric M. Nienaber, Christoph A. Patel, Himanshu J. TI Outcomes of Patients Presenting With Acute Type A Aortic Dissection in the Setting of Prior Cardiac Surgery An Analysis From the International Registry of Acute Aortic Dissection SO CIRCULATION LA English DT Article; Proceedings Paper CT Scientific Sessions of the American-Heart-Association (AHA) CY NOV 03-07, 2012 CL Los Angeles, CA SP Amer Heart Assoc DE aorta; aortic diseases; mortality; thoracic; thoracic surgery ID ASCENDING AORTA; MANAGEMENT AB Background-Prior cardiac surgery (PCS) can complicate the presentation and management of patients with type A acute aortic dissection (TAAAD). This report from the International Registry of Acute Aortic Dissection examines this hypothesis. Methods and Results-A total of 352 of 2196 patients with TAAAD (16%) enrolled in the International Registry of Acute Aortic Dissection had cardiac surgery before dissection, including coronary artery bypass grafting (34%), aortic or mitral valve surgery (36%), aortic surgery (42%), and other cardiac surgery (16%). Those with PCS were older, had a higher frequency of diabetes mellitus, hypertension, and atherosclerosis, and presented later from symptom onset to hospital presentation and diagnosis (all P<0.05). In-hospital mortality was significantly higher for PCS patients (34% versus 23%; P<0.001). Five-year mortality was independently predicted by PCS (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.05-3.95), age >70 years (HR, 2.65; 95% CI, 1.40-5.05), medical management (HR, 5.10; 95% CI, 2.43-10.71), distal communication (HR, 2.64; 95% CI, 1.35-5.14), and coma (HR, 9.50; 95% CI, 2.05-44.05). Among patients with PCS, in-hospital (43% medical versus 30% surgical; P=0.033) and intermediate-term mortality was higher in patients with medical versus surgical management. Propensity-matched analysis revealed significant increase in mortality with medical management, but not with PCS. Conclusions-PCS delays presentation, diagnosis, and treatment of TAAAD and is an important adverse risk factor for early and intermediate-term mortality. This effect may be because of increased medical management in this patient population. C1 [Teman, Nicholas R.; Deeb, George Michael; Patel, Himanshu J.] Univ Michigan Hlth Syst, Dept Cardiac Surg, Ann Arbor, MI USA. [Eagle, Kim A.] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Montgomery, Daniel G.] Univ Michigan Hlth Syst, Michigan Cardiovasc Outcomes Res & Reporting Prog, Ann Arbor, MI USA. [Peterson, Mark D.] St Michaels Hosp, Dept Surg, Toronto, ON M5B 1W8, Canada. [Russo, Mark J.] Univ Chicago, Med Ctr, Dept Surg, Chicago, IL 60637 USA. [Ehrlich, Marek P.] Univ Vienna, Dept Cardiothorac Surg, Vienna, Austria. [Myrmel, Truls] Univ Tromso Hosp, Dept Clin Med, N-9012 Tromso, Norway. [Upchurch, Gilbert R., Jr.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA USA. [Greason, Kevin] Mayo Clin, Dept Cardiovasc Surg, Rochester, MN USA. [Fillinger, Mark] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA. [Forteza, Alberto] Hosp Univ 12 Octubre, Dept Cardiac Surg, Madrid, Spain. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Hosp Eppendorf Rostock, Dept Cardiol, Rostock, Germany. RP Patel, HJ (reprint author), Univ Michigan, Dept Cardiac Surg, Ctr Cardiovasc, Cardiovasc Ctr 5144, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM hjpatel@med.umich.edu NR 14 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 10 PY 2013 VL 128 IS 11 SU 1 BP S180 EP S185 DI 10.1161/CIRCULATIONAHA.112.000342 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 301MD UT WOS:000330535500022 PM 24030404 ER PT J AU Langer-Gould, AM Anderson, WE Armstrong, MJ Cohen, AB Eccher, MA Iverson, DJ Potrebic, SB Becker, A Larson, R Gedan, A Getchius, TSD Gronseth, GS AF Langer-Gould, Annette M. Anderson, Wayne E. Armstrong, Melissa J. Cohen, Adam B. Eccher, Matthew A. Iverson, Donald J. Potrebic, Sonja B. Becker, Amanda Larson, Rod Gedan, Alicia Getchius, Thomas S. D. Gronseth, Gary S. TI The American Academy of Neurology's Top Five Choosing Wisely recommendations SO NEUROLOGY LA English DT Article ID CAROTID-ARTERY STENOSIS; ACUTE MIGRAINE; MULTIPLE-SCLEROSIS; RESCUE THERAPY; CONTROLLED-TRIAL; ENDARTERECTOMY; GUIDELINES; HEADACHE; SYNCOPE; SUBCOMMITTEE AB Objective: To discuss the American Academy of Neurology (AAN)'s Top Five Recommendations in the Choosing Wisely campaign promoting high-value neurologic medicine and physician-patient communication. The AAN published its Top Five Recommendations in February 2013 in collaboration with the American Board of Internal Medicine Foundation and Consumer Reports. Methods: A Choosing Wisely Working Group of 10 AAN members was formed to oversee the process and craft the evidence-based recommendations. AAN members were solicited for recommendations, the recommendations were sent out for external review, and the Working Group members (article authors) used a modified Delphi process to select their Top Five Recommendations. Results and recommendations: The Working Group submitted 5 neurologic recommendations to the AAN Practice Committee and Board of Directors; all 5 were approved by both entities in September 2012. Recommendation 1: Don't perform EEGs for headaches. Recommendation 2: Don't perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. Recommendation 3: Don't use opioids or butalbital for treatment of migraine, except as a last resort. Recommendation 4: Don't prescribe interferon-beta or glatiramer acetate to patients with disability from progressive, nonrelapsing forms of multiple sclerosis. Recommendation 5: Don't recommend carotid endarterectomy for asymptomatic carotid stenosis unless the complication rate is low (<3%). C1 [Langer-Gould, Annette M.] Los Angeles Med Ctr, Dept Neurol, Los Angeles, CA USA. [Potrebic, Sonja B.] Kaiser Permanente So Calif, Med Grp, Los Angeles, CA USA. [Langer-Gould, Annette M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Anderson, Wayne E.] Calif Pacific Neurosci Inst, San Francisco, CA USA. [Armstrong, Melissa J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Cohen, Adam B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Eccher, Matthew A.] Geisinger Med Ctr, Danville, PA 17822 USA. [Iverson, Donald J.] Humboldt Neurol Med Grp Inc, Eureka, CA USA. [Becker, Amanda; Larson, Rod; Gedan, Alicia; Getchius, Thomas S. D.] Amer Acad Neurol, Minneapolis, MN USA. [Gronseth, Gary S.] Univ Kansas, Med Ctr, Kansas City, KS USA. EM tgetchius@aan.com FU Biogen-Idec; Hoffman LaRoche; NIH; National MS Society; NCI; Toronto Western Hospital Morton; Gloria Shulman Movement Disorders Clinic; Edmond J. Safra Program in Parkinson's Disease; Abbott; Center for Integration of Medicine and Innovative Technology; Kaiser FX A.M. Langer-Gould serves as a site PI for 2 clinical trials sponsored by Biogen-Idec and Hoffman LaRoche and a diagnostic assay observational study sponsored by Biogen-Idec. Dr. Langer-Gould was formerly a lecturer at Stanford University and currently is also a Clinical Assistant Professor at the University of Southern California. She currently receives grant support from NIH and the National MS Society. Dr. Langer-Gould's husband was formerly an Associate Professor at Stanford University and the University of Southern California. Dr. Langer-Gould's husband was formally a VA employee and currently receives grant support from NIH and NCI. W. E. Anderson serves on the following advisory boards: Depomed, Insys Therapeutics, and Teva. Dr. Anderson receives funding for travel to meetings where he is invited to speak. Dr. Anderson serves as an advisory member of the Online Team of the American Headache Society. Dr. Anderson receives honoraria from a speaker's bureau for Teva, Insys Therapeutics, Pfizer, and Depomed. M.J. Armstrong serves on the Level of Evidence editorial board for Neurology. Dr. Armstrong received fellowship support as an Edmond J. Safra Fellow at the Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease in the last 24 months and receives research funding from Abbott as a study subinvestigator. A. B. Cohen receives royalties from Borm Bruckmeier Publishing, LLC, for neurology-related pocket cards and electronic applications. Dr. Cohen has received research support from the Center for Integration of Medicine and Innovative Technology. M. A. Eccher has nothing to disclose. D. J. Iverson serves as a NeuroPI editor and is also currently serving on Neurology Today's editorial board. Dr. Iverson is a member of Acorda Therapeutics' speaker's bureau. S. B. Potrebic receives honoraria for serving on the American Academy of Neurology Residency In-service Training Exam (RITE) workgroup. Dr. Potrebic has received internal Kaiser funding for biostatistician support for "Safety of Headache Medications in the Elderly." A. Becker is an employee of the American Academy of Neurology and has nothing to disclose. R. Larson is an employee of the American Academy of Neurology and has nothing to disclose. A. Gedan is an employee of the American Academy of Neurology and has nothing to disclose. T. Getchius is an employee of the American Academy of Neurology. Mr. Getchius's spouse is employed by Cigna Health Management. G. S. Gronseth serves on the Neurology Now editorial advisory board and was a member of Boehringer Ingelheim speaker's bureau until December 2011. Dr. Gronseth receives compensation from the American Academy of Neurology for serving as the Evidence-based Medicine Methodologist. Go to Neurology.org for full disclosures. NR 40 TC 23 Z9 23 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 10 PY 2013 VL 81 IS 11 BP 1004 EP 1011 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EI UT WOS:000330767700016 PM 23430685 ER PT J AU Hodi, FS Corless, CL Giobbie-Hurder, A Fletcher, JA Zhu, MJ Marino-Enriquez, A Friedlander, P Gonzalez, R Weber, JS Gajewski, TF O'Day, SJ Kim, KB Lawrence, D Flaherty, KT Luke, JJ Collichio, FA Ernstoff, MS Heinrich, MC Beadling, C Zukotynski, KA Yap, JT Van den Abbeele, AD Demetri, GD Fisher, DE AF Hodi, F. Stephen Corless, Christopher L. Giobbie-Hurder, Anita Fletcher, Jonathan A. Zhu, Meijun Marino-Enriquez, Adrian Friedlander, Philip Gonzalez, Rene Weber, Jeffrey S. Gajewski, Thomas F. O'Day, Steven J. Kim, Kevin B. Lawrence, Donald Flaherty, Keith T. Luke, Jason J. Collichio, Frances A. Ernstoff, Marc S. Heinrich, Michael C. Beadling, Carol Zukotynski, Katherine A. Yap, Jeffrey T. Van den Abbeele, Annick D. Demetri, George D. Fisher, David E. TI Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; PHASE-II TRIAL; METASTATIC MELANOMA; CLINICAL-EFFICACY; MESYLATE; AMPLIFICATION; EXPOSURE; SUBTYPES; GENE AB Purpose Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities. Patients and Methods We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Patients received imatinib 400 mg once per day or 400 mg twice per day if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening was performed by mass spectroscopy. Results Twenty-five patients were enrolled (24 evaluable). Eight patients (33%) had tumors with KIT mutations, 11 (46%) with KIT amplifications, and five (21%) with both. Median follow-up was 10.6 months (range, 3.7 to 27.1 months). Best overall response rate (BORR) was 29% (21% excluding nonconfirmed responses) with a two-stage 95% CI of 13% to 51%. BORR was significantly greater than the hypothesized null of 5% and statistically significantly different by mutation status (7 of 13 or 54% KIT mutated v 0% KIT amplified only). There were no statistical differences in rates of progression or survival by mutation status or by melanoma site. The overall disease control rate was 50% but varied significantly by KIT mutation status (77% mutated v 18% amplified). Four patients harbored pretreatment NRAS mutations, and one patient acquired increased KIT amplification after treatment. Conclusion Melanomas that arise on mucosal, acral, or CSD skin should be assessed for KIT mutations. Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib. (C) 2013 by American Society of Clinical Oncology C1 [Hodi, F. Stephen; Giobbie-Hurder, Anita; Friedlander, Philip; Luke, Jason J.; Zukotynski, Katherine A.; Yap, Jeffrey T.; Van den Abbeele, Annick D.; Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Fletcher, Jonathan A.; Zhu, Meijun; Marino-Enriquez, Adrian] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lawrence, Donald; Flaherty, Keith T.; Fisher, David E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Corless, Christopher L.; Heinrich, Michael C.; Beadling, Carol] Portland VA Med Ctr, Portland, OR USA. [Corless, Christopher L.; Heinrich, Michael C.; Beadling, Carol] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Friedlander, Philip] Mt Sinai Med Ctr, New York, NY 10029 USA. [Gonzalez, Rene] Univ Colorado, Ctr Canc, Aurora, CO USA. [Weber, Jeffrey S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Gajewski, Thomas F.] Univ Chicago, Chicago, IL 60637 USA. [O'Day, Steven J.] Beverly Hills Canc Ctr, Beverly Hills, CA USA. [Kim, Kevin B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Collichio, Frances A.] Univ N Carolina, Chapel Hill, NC USA. [Ernstoff, Marc S.] Geisel Sch Med, Hanover, NH USA. [Ernstoff, Marc S.] Dartmouth Coll, Hitchcock Med Ctr, Norris Cotton Canc Ctr, Hanover, NH 03756 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Stephen_Hodi@dfci.harvard.edu FU Novartis; Ron Gelb Melanoma Research Fund at Dana-Farber Cancer Institute; Veterans Administration Merit Review Grant [1I01BX000338-01]; Virginia and Daniel K. Ludwig Trust for Cancer Research FX Supported by Novartis, Ron Gelb Melanoma Research Fund at Dana-Farber Cancer Institute (F. S. H.), Veterans Administration Merit Review Grant No. 1I01BX000338-01 (M. C. H.), and Virginia and Daniel K. Ludwig Trust for Cancer Research (G. D. D.). Additional support was provided to G. D. D. and the Dana-Farber/Harvard Cancer Center by the Virginia and Daniel K. Ludwig Trust for Cancer Research. NR 33 TC 96 Z9 99 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2013 VL 31 IS 26 BP 3182 EP + DI 10.1200/JCO.2012.47.7836 PG 12 WC Oncology SC Oncology GA 301OF UT WOS:000330541000005 PM 23775962 ER PT J AU Batchelor, TT Mulholland, P Neyns, B Nabors, LB Campone, M Wick, A Mason, W Mikkelsen, T Phuphanich, S Ashby, LS DeGroot, J Gattamaneni, R Cher, L Rosenthal, M Payer, F Jurgensmeier, JM Jain, RK Sorensen, AG Xu, J Liu, Q van den Bent, M AF Batchelor, Tracy T. Mulholland, Paul Neyns, Bart Nabors, L. Burt Campone, Mario Wick, Antje Mason, Warren Mikkelsen, Tom Phuphanich, Surasak Ashby, Lynn S. DeGroot, John Gattamaneni, Rao Cher, Lawrence Rosenthal, Mark Payer, Franz Juergensmeier, Juliane M. Jain, Rakesh K. Sorensen, A. Gregory Xu, John Liu, Qi van den Bent, Martin TI Phase III Randomized Trial Comparing the Efficacy of Cediranib As Monotherapy, and in Combination With Lomustine, Versus Lomustine Alone in Patients With Recurrent Glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; ADJUVANT TEMOZOLOMIDE; CLINICAL-TRIALS; BRAIN-TUMORS; ANGIOGENESIS; GLIOMAS; VEGF; CHEMOTHERAPY; RADIOTHERAPY AB Purpose A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recentin in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma. Patients and Methods Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m(2)); (3) lomustine (110 mg/m(2)) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans. Results The primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone (hazard ratio [HR] = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90) or cediranib in combination with lomustine (HR = 0.76; 95% CI, 0.53 to 1.08; two-sided P = .16) versus lomustine based on independent or local review of postcontrast T1-weighted MRI. Conclusion This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma, although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects. (C) 2013 by American Society of Clinical Oncology C1 [Batchelor, Tracy T.; Jain, Rakesh K.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mulholland, Paul] UCL, London, England. [Gattamaneni, Rao] Christie Fdn Trust Hosp, Manchester, Lancs, England. [Neyns, Bart] Univ Ziekenhuis Brussel, Brussels, Belgium. [Nabors, L. Burt] Univ Alabama Birmingham, Birmingham, AL USA. [Campone, Mario] Ctr Rene Gauducheau, St Herblain, France. [Wick, Antje] Heidelberg Univ, Heidelberg, Germany. [Mason, Warren] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Phuphanich, Surasak] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Ashby, Lynn S.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [DeGroot, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cher, Lawrence] Austin Hlth Canc Serv, Melbourne, Vic, Australia. [Rosenthal, Mark] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Payer, Franz] Med Univ, Graz, Austria. [Juergensmeier, Juliane M.; Xu, John; Liu, Qi] AstraZeneca, Wilmington, DE USA. [van den Bent, Martin] Erasmus Univ, Med Ctr, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org FU AstraZeneca; Millennium; Pfizer; Mario Campone; Novartis; Boehringer Ingelheim; Apogenix; Eli Lilly; Roche; Merck; Celgene; Genetech Oncology; ImmunoCellular Therapeutics; Diffusion Pharmaceutical; Med-Immune; Myrexis; Sanofi-Aventis; EMD-Serono; Dyax FX Tracy T. Batchelor, AstraZeneca, Millennium, Pfizer; Paul Mulholland, AstraZeneca; Mario Campone, Novartis; Antje Wick, Boehringer Ingelheim, Apogenix, Eli Lilly; Tom Mikkelsen, Roche, Merck, Celgene; Surasak Phuphanich, AstraZeneca, Genetech Oncology, ImmunoCellular Therapeutics, Diffusion Pharmaceutical, Med-Immune, Boehringer Ingelheim, Myrexis; John DeGroot, Astra Zeneca, Sanofi-Aventis, EMD-Serono; Lawrence Cher, Astra Zeneca, Roche; Juliane M. Jurgensmeier, AstraZeneca; Rakesh K. Jain, MedImmune, Roche, Dyax; A. Gregory Sorensen, Astra Zeneca; Martin van den Bent, Roche NR 24 TC 136 Z9 139 U1 3 U2 14 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2013 VL 31 IS 26 BP 3212 EP 3218 DI 10.1200/JCO.2012.47.2464 PG 7 WC Oncology SC Oncology GA 301OF UT WOS:000330541000010 PM 23940216 ER PT J AU Richard, EM Thiyagarajan, T Bunni, MA Basher, F Roddy, PO Siskind, LJ Nietert, PJ Nowling, TK AF Richard, Erin Morris Thiyagarajan, Thirumagal Bunni, Marlene A. Basher, Fahmin Roddy, Patrick O. Siskind, Leah J. Nietert, Paul J. Nowling, Tamara K. TI Reducing FLI1 Levels in the MRL/lpr Lupus Mouse Model Impacts T Cell Function by Modulating Glycosphingolipid Metabolism SO PLOS ONE LA English DT Article ID TRANSCRIPTION FACTOR; CYTOKINE PRODUCTION; RENAL-DISEASE; ETS FAMILY; DECREASED EXPRESSION; ANTIGEN RECEPTOR; MURINE LUPUS; MICE; ERYTHEMATOSUS; LYMPHOCYTES AB Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by abnormalities in cells of the immune system including B and T cells. Genetically reducing globally the expression of the ETS transcription factor FLI1 by 50% in two lupus mouse models significantly improves disease measures and survival through an unknown mechanism. In this study we analyze the effects of reducing FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that adoptive transfer of MRL/lpr Fli1(+/+) or Fli1(+/-) T cells and B cells into Rag1-deficient mice results in significantly decreased serum immunoglobulin levels in animals receiving Fli1(+/-) lupus T cells compared to animals receiving Fli1(+/+) lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1(+/-) T cells produce significantly less IL-4 during early and late disease and exhibited significantly decreased TCR-specific activation during early disease compared to Fli1(+/+) T cells. Moreover, the Fli1(+/-) T cells expressed significantly less neuraminidase 1 (Neu1) message and decreased NEU activity during early disease and significantly decreased levels of glycosphingolipids during late disease compared to Fli1(+/+) T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse and human T cell lines. Together, our results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by decreasing TCR-specific activation and IL-4 production in part through the modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic pathway in lupus may serve as a therapeutic approach to treating lupus. C1 [Richard, Erin Morris; Thiyagarajan, Thirumagal; Basher, Fahmin; Nowling, Tamara K.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Bunni, Marlene A.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Nietert, Paul J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Roddy, Patrick O.; Siskind, Leah J.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Siskind, Leah J.; Nowling, Tamara K.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Nowling, TK (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. EM nowling@musc.edu FU Veteran's Administration [BX000115]; National Institutes of Health [NCRR P20 RR17677 COBRE, NIDDK R01 DK093462, NCRR UL1TR000062, NIAMS 1P60 AR062755-01]; Cancer Center Support Grant [P30 CA138313] FX These studies were supported by funding from the Veteran's Administration (Merit Review Grant BX000115 to TKN) and in part by National Institutes of Health (NCRR P20 RR17677 COBRE in Lipidomics and Pathobiology pilot project and NIDDK R01 DK093462 to LJS) and Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina supported by a Cancer Center Support Grant (P30 CA138313). Support for PJN was provided by the National Institutes of Health (NCRR UL1TR000062 and NIAMS 1P60 AR062755-01). The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 8 Z9 9 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 10 PY 2013 VL 8 IS 9 AR e75175 DI 10.1371/journal.pone.0075175 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259PK UT WOS:000327538600131 PM 24040398 ER PT J AU Tomio, K Kawana, K Taguchi, A Isobe, Y Iwamoto, R Yamashita, A Kojima, S Mori, M Nagamatsu, T Arimoto, T Oda, K Osuga, Y Taketani, Y Kang, JX Arai, H Arita, M Kozuma, S Fujii, T AF Tomio, Kensuke Kawana, Kei Taguchi, Ayumi Isobe, Yosuke Iwamoto, Ryo Yamashita, Aki Kojima, Satoko Mori, Mayuyo Nagamatsu, Takeshi Arimoto, Takahide Oda, Katsutoshi Osuga, Yutaka Taketani, Yuji Kang, Jing X. Arai, Hiroyuki Arita, Makoto Kozuma, Shiro Fujii, Tomoyuki TI Omega-3 Polyunsaturated Fatty Acids Suppress the Cystic Lesion Formation of Peritoneal Endometriosis in Transgenic Mouse Models SO PLOS ONE LA English DT Article ID MEDIATOR RESOLVIN E1; IRON OVERLOAD; MICE RICH; INFLAMMATION; FLUID; MACROPHAGES; EXPRESSION; WOMEN; OMEGA-3-FATTY-ACIDS; 12/15-LIPOXYGENASE AB Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis. C1 [Tomio, Kensuke; Kawana, Kei; Taguchi, Ayumi; Yamashita, Aki; Kojima, Satoko; Mori, Mayuyo; Nagamatsu, Takeshi; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Taketani, Yuji; Kozuma, Shiro; Fujii, Tomoyuki] Univ Tokyo, Fac Med, Dept Obstet & Gynecol, Tokyo 113, Japan. [Isobe, Yosuke; Iwamoto, Ryo; Arai, Hiroyuki; Arita, Makoto] Univ Tokyo, Dept Hlth Chem, Grad Sch Pharmaceut Sci, Tokyo 113, Japan. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Kawana, K (reprint author), Univ Tokyo, Fac Med, Dept Obstet & Gynecol, Tokyo 113, Japan. EM kkawana-tky@umin.org; marita@mol.f.u-tokyo.ac.jp FU Tokyo IGAKUKAI; Japan Science and Technology agency Precursory Research for Embryonic Science and Technology (PRESTO); Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This work was supported by Tokyo IGAKUKAI (KK) (http://square.umin.ac.jp/igakukai/02toppage/toppage.html); Japan Science and Technology agency Precursory Research for Embryonic Science and Technology (PRESTO) (MA) (http://www.inflam.jst.go.jp/); and The Ministry of Education, Culture, Sports, Science, and Technology of Japan (MA) (http://www.lipid.med.kyushu-u.ac.jp/). All of them are numberless. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 8 Z9 8 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 10 PY 2013 VL 8 IS 9 AR e73085 DI 10.1371/journal.pone.0073085 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259PK UT WOS:000327538600017 PM 24039864 ER PT J AU Hatano, H Somsouk, M Sinclair, E Harvill, K Gilman, L Cohen, M Hoh, R Hunt, PW Martin, JN Wong, JK Deeks, SG Yukl, SA AF Hatano, Hiroyu Somsouk, Ma Sinclair, Elizabeth Harvill, Kara Gilman, Lee Cohen, Michelle Hoh, Rebecca Hunt, Peter W. Martin, Jeffrey N. Wong, Joseph K. Deeks, Steven G. Yukl, Steven A. TI Comparison of HIV DNA and RNA in gut-associated lymphoid tissue of HIV-infected controllers and noncontrollers SO AIDS LA English DT Article DE controllers; gut-associated lymphoid tissue; HIV; viral reservoir ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; SUPPRESSIVE ANTIRETROVIRAL THERAPY; LOW-LEVEL VIREMIA; ELITE CONTROLLERS; TYPE-1 RNA; REPLICATION; PLASMA; INDIVIDUALS; ACTIVATION AB Objectives:HIV-infected controllers have provided novel insights into mechanisms of viral control. We investigated the degree to which HIV DNA and RNA are present in gut-associated lymphoid tissue (GALT) of controllers. Design:Cross-sectional cohort study. Methods:Colorectal biopsy pieces were obtained from five untreated noncontrollers, five ART-suppressed patients, and nine untreated controllers. Results:Rectal HIV DNA was lower in controllers (median 496copies/10(6) CD4(+) T cells) than in untreated noncontrollers (117483copies/10(6) CD4(+) T cells, P=0.001) and ART-suppressed patients (6116copies/10(6) CD4(+) T cells, P=0.004). Similarly, rectal HIV RNA was lower in controllers (19copies/10(6) CD4(+) T cells) than in noncontrollers (15210copies/10(6) CD4(+) T cells, P=0.001) and ART-suppressed patients (1625copies/10(6) CD4(+) T cells, P=0.0599). Rectal HIV RNA/DNA ratios were not statistically different between the three groups. Conclusion:Despite being able to maintain very low plasma HIV RNA levels in the absence of antiretroviral therapy (ART), HIV-infected controllers have readily measurable levels of HIV DNA and RNA in GALT. As expected, controllers had lower rectal HIV DNA and RNA compared with untreated noncontrollers and ART-suppressed individuals. Compared with the mechanisms of natural' viral control of controllers, long-term ART does not reduce the total HIV reservoir to the level of controllers. C1 [Hatano, Hiroyu; Somsouk, Ma; Sinclair, Elizabeth; Harvill, Kara; Gilman, Lee; Cohen, Michelle; Hoh, Rebecca; Hunt, Peter W.; Wong, Joseph K.; Deeks, Steven G.; Yukl, Steven A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA. [Wong, Joseph K.; Yukl, Steven A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hatano, H (reprint author), San Francisco Gen Hosp, Bldg 80,Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA. EM hhatano@php.ucsf.edu FU National Institute of Allergy and Infectious Diseases [R01 AI087145, K23 AI075985, K24 AI069994, R56 AI091573, R01 NS051132]; National Cancer Institute [K23 CA157929]; Delaney AIDS Research Enterprise (DARE) [U19 AI0961090]; California HIV/AIDS Research Program [ID08-SF-004]; American Foundation for AIDS Research [106710-40-RGRL]; UCSF/Gladstone Institute of Virology & Immunology CFAR [P30 AI027763]; UCSF Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]; Center for AIDS Prevention Studies [P30 MH62246]; CFAR Network of Integrated Systems [R24 AI067039]; U.S. Department of Veterans Affairs [1 IK2 CX000520-01, 5101BX001048] FX This work was supported by grants from the National Institute of Allergy and Infectious Diseases (R01 AI087145, K23 AI075985, K24 AI069994, R56 AI091573, R01 NS051132), the National Cancer Institute (K23 CA157929), the Delaney AIDS Research Enterprise (DARE; U19 AI0961090), California HIV/AIDS Research Program (grant number ID08-SF-004), American Foundation for AIDS Research (106710-40-RGRL), the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), the Center for AIDS Prevention Studies (P30 MH62246), the CFAR Network of Integrated Systems (R24 AI067039), and the U.S. Department of Veterans Affairs (1 IK2 CX000520-01, 5101BX001048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. NR 30 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD SEP 10 PY 2013 VL 27 IS 14 BP 2255 EP 2260 DI 10.1097/QAD.0b013e328362692f PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 248LZ UT WOS:000326702700012 PM 24157906 ER PT J AU Driver, TH Scherzer, R Peralta, CA Tien, PC Estrella, MM Parikh, CR Butch, AW Anastos, K Cohen, MH Nowicki, M Sharma, A Young, MA Abraham, A Shlipak, MG AF Driver, Todd H. Scherzer, Rebecca Peralta, Carmen A. Tien, Phyllis C. Estrella, Michelle M. Parikh, Chirag R. Butch, Anthony W. Anastos, Kathryn Cohen, Mardge H. Nowicki, Marek Sharma, Anjali Young, Mary A. Abraham, Alison Shlipak, Michael G. TI Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women SO AIDS LA English DT Article DE creatinine; cystatin C; glomerular filtration rate; HIV; kidney; mortality; women ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR EVENTS; SERUM CREATININE; HIV-1-INFECTED PATIENTS; ELDERLY PERSONS; INTERAGENCY HIV; RISK; MUSCLE AB Background:Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine. Design:Retrospective cohort analysis. Methods:Cystatin C and creatinine were measured from specimens taken and stored during the 1999-2000 examination among 908 HIV-infected participants in the Women's Interagency HIV study (WIHS). Mean follow-up was 10.2 years. Predictors of differential glomerular filtration rate (GFR) estimates were evaluated with multivariable linear regression. The associations of baseline categories (<60, 60-90, and >90ml/min per 1.73m(2)) of creatinine estimated GFR (eGFR(cr)), cystatin C eGFR (eGFR(cys)), and combined creatinine-cystatin C eGFR (eGFR(cr-cys)) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging. Results:CKD risk factors were associated with lower eGFR(cys) and eGFR(cr-cys) values compared with eGFR(cr). Relative to eGFR more than 90, the eGFR less than 60 category by eGFR(cys) (Adjusted hazard ratio: 2.56; 95% confidence interval: 1.63-4.02), eGFR(cr-cys) (3.11; 1.94-5.00), and eGFR(cr) (2.34; 1.44-3.79) was associated with increased mortality risk. However, the eGFR 60-90 category was associated with increased mortality risk for eGFR(cys) (1.80; 1.28-2.53) and eGFR(cr-cys) (1.91; 1.38-2.66) but not eGFR(cr) (1.20; 0.85-1.67). The overall NRI for mortality was 26% when reclassifying from eGFR(cr) to eGFR(cys) (P<0.001) and was 20% when reclassifying from eGFR(cr) to eGFR(cr-cys) (P<0.001). Conclusion:The addition of cystatin C may improve mortality risk prediction by stages of kidney function relative to creatinine. CKD risk factors are associated with an overestimate of GFR by serum creatinine relative to cystatin C. C1 [Driver, Todd H.] Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Scherzer, Rebecca; Peralta, Carmen A.; Tien, Phyllis C.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Peralta, Carmen A.; Tien, Phyllis C.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Estrella, Michelle M.; Abraham, Alison] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Nephrol Sect, New Haven, CT 06520 USA. [Parikh, Chirag R.] Yale Univ, Program Appl Translat Res, New Haven, CT USA. [Butch, Anthony W.] Univ Calif Los Angeles, Clin Immunol Res Lab, Los Angeles, CA USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Med & Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Nowicki, Marek] Univ So Calif, Los Angeles, CA USA. [Sharma, Anjali] Suny Downstate Med Ctr, Dept Med, Div Infect Dis, Brooklyn, NY 11203 USA. [Young, Mary A.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU UCSF-CTSI [TL1 TR000144]; [R01 AG034853-03] FX Sources of Support: R01 AG034853-03 (Shlipak); UCSF-CTSI Grant Number TL1 TR000144 (Driver). NR 48 TC 12 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD SEP 10 PY 2013 VL 27 IS 14 BP 2291 EP 2299 DI 10.1097/QAD.0b013e328362e874 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 248LZ UT WOS:000326702700016 PM 23669156 ER PT J AU Sarode, R Milling, TJ Refaai, MA Mangione, A Schneider, A Durn, BL Goldstein, JN AF Sarode, Ravi Milling, Truman J., Jr. Refaai, Majed A. Mangione, Antoinette Schneider, Astrid Durn, Billie L. Goldstein, Joshua N. TI Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding A Randomized, Plasma-Controlled, Phase IIIb Study SO CIRCULATION LA English DT Article DE vitamin K antagonist; hemorrhage; prothrombin complex concentrates; plasma; anticoagulants ID FRESH-FROZEN PLASMA; PREVIOUSLY UNTREATED PATIENTS; ORAL ANTICOAGULANT REVERSAL; RECOMBINANT FACTOR-VIII; INTRACRANIAL HEMORRHAGE; CLINICAL-TRIAL; HEMOPHILIA-A; WARFARIN; TRANSFUSION; THERAPY AB Background- Background- Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal. Methods and Results- Methods and Results- In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (<= 1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8-20.0) for the 4F-PCC group and 3.60 (1.9-38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, -5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P < 0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced >= 1 adverse event. Conclusions- Conclusions- 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels. Clinical Trial Registration- Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708435. C1 [Sarode, Ravi] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Milling, Truman J., Jr.] Seton Univ Texas Southwestern, Clin Res Inst Austin, Univ Med Ctr Brackenridge, Dell Childrens Med Ctr, Austin, TX USA. [Refaai, Majed A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Mangione, Antoinette; Durn, Billie L.] CSL Behring LLC, King Of Prussia, PA USA. [Schneider, Astrid] CSL Behring GmbH, Marburg, Germany. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sarode, R (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pathol, Transfus Med & Hemostasis Reference Lab, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM ravi.sarode@utsouthwestern.edu RI Goldstein, Joshua/H-8953-2016 FU CSL Behring FX This research was sponsored by CSL Behring. A steering committee of investigators, academic medical experts, and representatives of the sponsor oversaw the trial design and conduct with the assistance of the independent Data Safety Monitoring Board, SAB, and EAB. The sponsor participated in the selection of the board members. The sponsor was responsible for data processing, management, analysis of the data according to a predefined statistical analysis plan, and reporting of the results. Editorial assistance was funded by the sponsor. All authors had access to the data and jointly decided to submit the manuscript for publication. All authors contributed to interpretation of data and drafting of the manuscript. The authors vouch for the accuracy and completeness of the reported data and analyses, as well as the fidelity of this report to the protocol. All authors read and approved the final manuscript for publication. NR 39 TC 173 Z9 174 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 10 PY 2013 VL 128 IS 11 BP 1234 EP 1243 DI 10.1161/CIRCULATIONAHA.113.002283 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 217RO UT WOS:000324377700021 PM 23935011 ER PT J AU Piccini, JP Stevens, SR Chang, YC Singer, DE Lokhnygina, Y Go, AS Patel, MR Mahaffey, KW Halperin, JL Breithardt, G Hankey, GJ Hacke, W Becker, RC Nessel, CC Fox, KAA Califf, RM AF Piccini, Jonathan P. Stevens, Susanna R. Chang, YuChiao Singer, Daniel E. Lokhnygina, Yuliya Go, Alan S. Patel, Manesh R. Mahaffey, Kenneth W. Halperin, Jonathan L. Breithardt, Guenter Hankey, Graeme J. Hacke, Werner Becker, Richard C. Nessel, Christopher C. Fox, Keith A. A. Califf, Robert M. CA ROCKET AF Steering Comm Investigat TI Response to Letter Regarding Article, "Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation: Validation of the R(2)CHADS(2) Index in the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study Cohorts" SO CIRCULATION LA English DT Letter C1 [Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Mahaffey, Kenneth W.; Becker, Richard C.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. [Chang, YuChiao; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, YuChiao; Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Go, Alan S.] Kaiser Permanente Div Res, Oakland, CA USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Breithardt, Guenter] Hosp Univ Munster, Munster, Germany. [Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. RP Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson Johnson; Boston Scientific; Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital; Bayer HealthCare; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Pfizer; Sanofi; Ortho McNeil Janssen; AstraZeneca; Bayer; Eli Lilly; GlaxoSmithKline; Merck; Momenta Pharmaceuticals; Novartis; Portola; Pozen; Regado Biotechnologies; Sanofi-Aventis; Medicines Company; Ortho/McNeill; Polymedix FX Dr Piccini reports receiving research grants from Johnson & Johnson and Boston Scientific and serves as a consultant to Medtronic, Forest Laboratories, Sanofi Aventis, and Johnson & Johnson. Dr Singer is supported, in part, by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital. He receives consulting fees from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, and Sanofi. Dr Patel receives honoraria from Johnson & Johnson and Bayer and consulting fees from Ortho McNeil Janssen and Bayer HealthCare and serves on an advisory board for Genzyme. Dr Mahaffey receives grant support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, Sanofi-Aventis, Schering-Plow (now Merck), and The Medicines Company. Dr Mahaffey receives consulting fees from AstraZeneca and Johnson & Johnson, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Ortho/McNeill, Pfizer, Polymedix, Sanofi-Aventis, and Schering-Plow (now Merck). Dr Halperin receives honoraria from Johnson & Johnson and Bayer and advisory fees from Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer. Dr Breithardt receives honoraria from Johnson & Johnson and Bayer and advisory board fees from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. Dr Hankey receives honoraria from Johnson & Johnson, Bayer, and Sanofi-Aventis and serves on the trial adjudication committees and an advisory board for Boehringer Ingelheim. Dr Hacke receives honoraria from Johnson & Johnson and Bayer and serves on an advisory board for Boehringer Ingelheim. Dr Becker receives research support from Bayer and Johnson & Johnson. Dr Nessel is an employee of Johnson & Johnson. Dr Fox receives research grants and honoraria from Bayer, Eli Lilly, Boehringer Ingelheim, Sanofi-Aventis, and GlaxoSmithKline. Dr Califf receives consulting fees and research funding from Johnson & Johnson. A full list of the disclosures for Drs Piccini, Patel, Mahaffey, and Califf are listed at www.dcri.org. S. Stevens and Drs Chang, Lokhnygina, and Go report no conflicts. NR 3 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 10 PY 2013 VL 128 IS 11 BP E172 EP E173 DI 10.1161/CIRCULATIONAHA.113.004013 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 217RO UT WOS:000324377700005 PM 24019452 ER PT J AU Foster, R Buckanovich, RJ Rueda, BR AF Foster, Rosemary Buckanovich, Ronald J. Rueda, Bo R. TI Ovarian cancer stem cells: Working towards the root of sternness SO CANCER LETTERS LA English DT Review DE Cancer stem cells; Ovarian cancer ID TUMOR-INITIATING CELLS; SIDE-POPULATION CELLS; MULLERIAN-INHIBITING SUBSTANCE; ALDEHYDE DEHYDROGENASE; BREAST-CANCER; FALLOPIAN-TUBE; MOUSE MODEL; EXPRESSION; IDENTIFICATION; CD133 AB Despite medical advances made over the past decade, ovarian cancer remains one of the more lethal gynecologic cancers in the United States. While current therapeutic strategies are relatively effective, there is a high incidence of recurrent chemoresistant disease. This has been attributed, in part, to a regenerative tumor cell sub-population that has acquired stem cell properties which allows these cells to escape standard chemotherapeutics and drive recurrent disease. To date, a number of laboratories have identified these cancer stem cell (CSC) sub-populations in ovarian cancer cell lines, tumors or ascites and the collective findings suggest ovarian CSCs are likely to be as heterogeneous as the disease itself. Moreover, the multiple ovarian histophenotypes and possible sites of disease origin together with the potential for differential hierarchal contributions of multiple CSCs populations represent significant challenges to the identification, functional characterization and therapeutic targeting of ovarian CSC. This review will highlight the markers and methodology currently used to identify and isolate these cells. We will discuss some of the underlying ovarian CSC biology, the signaling pathways implicated in their survival, replication and differentiation and potential therapeutic targeting strategies. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Buckanovich, Ronald J.] Univ Michigan, Cell & Mol Biol Program, Ann Arbor, MI 48109 USA. [Buckanovich, Ronald J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Buckanovich, Ronald J.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. RP Rueda, BR (reprint author), VCRB Massachusetts Gen Hosp, 55 Fruit St,Thr 901A, Boston, MA 02114 USA. EM brueda@partners.org NR 97 TC 30 Z9 31 U1 3 U2 21 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD SEP 10 PY 2013 VL 338 IS 1 SI SI BP 147 EP 157 DI 10.1016/j.canlet.2012.10.023 PG 11 WC Oncology SC Oncology GA 220ES UT WOS:000324565800022 PM 23138176 ER PT J AU Zavin, A Daniels, K Arena, R Allsup, K Lazzari, A Joseph, J Schulze, PC Lecker, SH Forman, DE AF Zavin, Alexandra Daniels, Karla Arena, Ross Allsup, Kelly Lazzari, Antonio Joseph, Jacob Schulze, P. Christian Lecker, Stewart H. Forman, Daniel E. TI Adiposity facilitates increased strength capacity in heart failure patients with reduced ejection fraction SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Physical function; Body composition; Adiposity ID BODY-MASS INDEX; OBESITY PARADOX; ASSOCIATION; MORTALITY; DISEASE; PROGNOSIS; COHORT; ADULTS; SIZE; FAT AB Background: Obesity is associated with relatively improved prognosis among heart failure (HF) patients. Mechanisms explaining this so-called "obesity paradox" have been unclear. We hypothesized that increased adiposity may contribute to increased strength capacity, and may thereby facilitate clinical benefits. Methods and results: In a controlled, cross-sectional study, adults aged >= 50 years with HF with reduced ejection fraction (HFREF) (LVEF <= 40%) were compared to age matched controls. Body composition was determined by dual-energy X-ray absorptiometry (DXA). Aerobic (cardiopulmonary exercise testing), maximum strength (one repetition maximum [1RM]), and power (submaximal resistance/time) were assessed. 70 adults (31 HFREF, 39 controls; mean age 66.2 +/- 9.6 years) were studied. Peak oxygen consumption (VO2) (15.4 +/- 4.2 vs. 23.4 +/- 6.6 ml O-2 center dot kg(-1).min(-1), p<0.0001), 1RM (154.8 +/- 52.0 vs. 195.3 +/- 56.8 kg, p<0.01) and power (226.4 +/- 99.2 vs. 313.3 +/- 130.6, p<0.01) were lower in HFREF vs. controls. 1RM correlated with total fat (r=0.56, p<0.01), leg fat (r=0.45, p<0.05) and arm fat (r=0.39, p<0.05) in HFREF. Moreover, among HFREF patients with a high (<30 kg/m(2)) body mass index (BMI), 1RM and fat mass were significantly greater than those with lower (<30 kg/m(2)) BMIs. Correlations between 1RM and total fat (r=0.65, p<0.05) and leg fat (r=0.64, p<0.05) were particularly notable in the high BMI subgroup. Conclusion: Increased adiposity correlates with relatively greater strength in HFREF patients which may explain some of the clinical benefits that result from obesity. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Zavin, Alexandra; Daniels, Karla; Allsup, Kelly; Forman, Daniel E.] VA Boston Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Arena, Ross] Univ New Mexico, Sch Med, Dept Orthopaed & Rehabil, Phys Therapy Program,Div Cardiol, Albuquerque, NM 87131 USA. [Arena, Ross] Univ New Mexico, Sch Med, Dept Internal Med, Div Cardiol, Albuquerque, NM 87131 USA. [Lazzari, Antonio] VA Boston Healthcare Syst, Div Rheumatol, Boston, MA USA. [Lazzari, Antonio] Boston Univ, Sch Med, Boston, MA 02118 USA. [Joseph, Jacob; Forman, Daniel E.] VA Boston Healthcare Syst, Div Cardiovasc Med, Boston, MA USA. [Schulze, P. Christian] Columbia Univ, Med Ctr, Div Cardiovasc Med, New York, NY USA. [Lecker, Stewart H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02115 USA. [Joseph, Jacob; Forman, Daniel E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM deforman@partners.org RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 FU VA Merit Award [F4726R] FX This study was funded by: VA Merit Award F4726R, Ubiquitin Proteolysis and PGC-1 alpha in Skeletal Muscle in Heart Failure. NR 29 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 10 PY 2013 VL 167 IS 6 BP 2468 EP 2471 DI 10.1016/j.ijcard.2012.06.007 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 219BH UT WOS:000324478400029 PM 22743190 ER PT J AU Lopes, RD White, JA Tricoci, P White, HD Armstrong, PW Braunwald, E Giugliano, RP Harrington, RA Lewis, BS Brogan, GX Gibson, CM Califf, RM Newby, LK AF Lopes, Renato D. White, Jennifer A. Tricoci, Pierluigi White, Harvey D. Armstrong, Paul W. Braunwald, Eugene Giugliano, Robert P. Harrington, Robert A. Lewis, Basil S. Brogan, Gerard X., Jr. Gibson, C. Michael Califf, Robert M. Newby, L. Kristin TI Age, treatment, and outcomes in high-risk non-ST-segment elevation acute coronary syndrome patients: Insights from the EARLY ACS trial SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Acute coronary syndromes; Glycoprotein IIb/IIIa inhibitor; Elderly ID GLYCOPROTEIN IIB/IIIA INHIBITORS; HEART-ASSOCIATION COUNCIL; HEALTH-CARE PROFESSIONALS; ELDERLY-PATIENTS; MYOCARDIAL-INFARCTION; GLOBAL REGISTRY; ANTITHROMBOTIC STRATEGY; SCIENTIFIC STATEMENT; GERIATRIC-CARDIOLOGY; CLINICAL CARDIOLOGY AB Background: Elderly patients with acute coronary syndromes (ACS) are at high risk for death and recurrent thrombotic events. We evaluated the efficacy and safety of intensive treatment with glycoprotein IIb/IIIa inhibitors in an elderly population, and the relationships between age, timing of administration, and clinical outcomes. Methods: We used data from high-risk non-ST-segment elevation ACS patients randomized to early eptifibatide vs. delayed provisional use at percutaneous coronary intervention. In multivariable models, we included agextreatment interaction terms to assess whether treatment effect varied by age after adjusting for confounders. Results: Of 9406 patients, 13.9% were aged <55 years; 27.6%, 55-64 years; 33.2%, 65-74 years; and 25.3%, >= 75 years. For each 10-year age increase, the adjusted odds ratio (OR) (95% confidence interval [CI]) for 96-hour death, myocardial infarction (MI), recurrent ischemia requiring urgent revascularization, or thrombotic bailout was 1.13 (1.04-1.23) and for 30-day death or MI was 1.13 (1.04-1.22). Increasing age was also associated with greater 1-year mortality (adjusted hazard ratio per 10 years: 1.44, 95% CI 1.30-1.60). There was no interaction between age and treatment (p interaction=0.99, 0.54, and 0.87, respectively). Increasing age was associated with more non-coronary artery bypass grafting-related TIMI major bleeding (adjusted OR and 95% CI per 10 years: 1.54 [1.24-1.92]), GUSTO moderate/severe bleeding (1.52 [1.33-1.75]), and transfusion (1.25 [1.07-1.45]). The amount by which TIMI major bleeding was increased with early vs. delayed provisional eptifibatide use was significantly greater with increasing age (p interaction=0.02), but the agextreatment interactions were not significant for GUSTO moderate/severe bleeding or transfusion (p interaction=0.33 and 0.54, respectively). Conclusion: Increasing age was associated with greater risk for ischemic events and more bleeding. Despite higher baseline ischemic risk in older patients, there was no preferential benefit of early vs. delayed provisional eptifibatide use for ischemic outcomes as age increased, but the incremental bleeding risk was amplified. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Lopes, Renato D.; White, Jennifer A.; Tricoci, Pierluigi; Harrington, Robert A.; Califf, Robert M.; Newby, L. Kristin] Duke Clin Res Inst, Durham, NC 27705 USA. [White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. [Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada. [Braunwald, Eugene; Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Lewis, Basil S.] Lady Davis Carmel Med Ctr, Haifa, Israel. [Brogan, Gerard X., Jr.] NYU, Sch Med, Dept Clin Emergency Med, New York, NY USA. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Lopes, RD (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 0311,Terrace Level, Durham, NC 27705 USA. EM renato.lopes@duke.edu FU Merck Co., Inc.; Merck & Company, Inc., Whitehouse Station, NJ, USA FX The EARLY ACS trial was funded by Schering-Plough Corporation (now Merck & Co., Inc.). These analyses were funded by research grant support from Merck & Company, Inc., Whitehouse Station, NJ, USA. NR 28 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 10 PY 2013 VL 167 IS 6 BP 2580 EP 2587 DI 10.1016/j.ijcard.2012.06.053 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 219BH UT WOS:000324478400046 PM 22795720 ER PT J AU Hage, FG Wackers, FJT Bansal, S Chyun, DA Young, LH Inzucchi, SE Iskandrian, AE AF Hage, Fadi G. Wackers, Frans J. Th Bansal, Shanti Chyun, Deborah A. Young, Lawrence H. Inzucchi, Silvio E. Iskandrian, Ami E. TI The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Type 2 diabetes mellitus; Heart rate; Adenosine; Myocardial perfusion imaging; Autonomic function ID CARDIOVASCULAR AUTONOMIC NEUROPATHY; MYOCARDIAL-ISCHEMIA; DIAD; REGADENOSON; MELLITUS; RISK; DIPYRIDAMOLE; ASSOCIATION; DYSFUNCTION; MORTALITY AB Background: The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk. Methods: In DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR <20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death. Results: During 4.7+/-0.9 years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR <20% (n=79), 20-39% (n=182) and >= 40% (n=257), respectively, p=0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model <0.001). HRR <20% was associated with 9-fold increased risk (p=0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p=0.004). Participants with both abnormal MPI and HRR (n=8) were at highest risk for cardiac events (38%) whereas those with HRR >= 40%, irrespective of MPI abnormalities (n=234), were at extremely low risk (>= 1%, log-rank p<0.001). Conclusions: In DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Hage, Fadi G.; Iskandrian, Ami E.] Univ Alabama Birmingham, Birmingham, AL USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Wackers, Frans J. Th; Bansal, Shanti; Young, Lawrence H.; Inzucchi, Silvio E.] Yale Univ, Sch Med, New Haven, CT USA. [Chyun, Deborah A.] NYU, New York, NY USA. RP Hage, FG (reprint author), Zeigler Res Bldg 1024,703 19th St South, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU General Clinical Research Centers at Yale University (National Institutes of Health) [M01-RR-00125]; University of Rochester [NIH 5M01-RR-00847]; Tulane University [NIH 6M01-RR-05096] FX Financial disclosure: This work was performed with the support of the General Clinical Research Centers at Yale University (National Institutes of Health M01-RR-00125), University of Rochester (NIH 5M01-RR-00847), and Tulane University (NIH 6M01-RR-05096). NR 21 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 10 PY 2013 VL 167 IS 6 BP 2952 EP 2957 DI 10.1016/j.ijcard.2012.08.011 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 219BH UT WOS:000324478400102 PM 22981277 ER PT J AU Ozcan, C Barrett, CD AF Ozcan, Cevher Barrett, Conor D. TI Utility of intracardiac echocardiography for catheter ablation of an anteroseptal accessory pathway from the non-coronary aortic cusp SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Intracardiac echocardiography; Wolf Parkinson White; Atrioventricular reentrant tachycardia; Catheter ablation; Aortic non-coronary cusp; Accessory pathway ID TACHYCARDIA; SINUS C1 [Ozcan, Cevher; Barrett, Conor D.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ozcan, Cevher] SUNY Buffalo, Div Cardiovasc Med, Sch Med & Biomed Sci, Buffalo, NY 14203 USA. RP Ozcan, C (reprint author), SUNY Buffalo, Div Cardiovasc Med, Sch Med & Biomed Sci, Clin & Translat Res Ctr, 7th Floor,875 Ellicott St, Buffalo, NY 14203 USA. EM cevheroz@buffalo.edu NR 9 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 10 PY 2013 VL 167 IS 6 BP E153 EP E155 DI 10.1016/j.ijcard.2013.04.050 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 219BH UT WOS:000324478400001 PM 23664440 ER PT J AU Carroll, JD Edwards, FH Marinac-Dabic, D Brindis, RG Grover, FL Peterson, ED Tuzcu, EM Shahian, DM Rumsfeld, JS Shewan, CM Hewitt, K Holmes, DR Mack, MJ AF Carroll, John D. Edwards, Fred H. Marinac-Dabic, Danica Brindis, Ralph G. Grover, Frederick L. Peterson, Eric D. Tuzcu, E. Murat Shahian, David M. Rumsfeld, John S. Shewan, Cynthia M. Hewitt, Kathleen Holmes, David R., Jr. Mack, Michael J. TI The STS-ACC Transcatheter Valve Therapy National Registry A New Partnership and Infrastructure for the Introduction and Surveillance of Medical Devices and Therapies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE aortic stenosis; mitral regurgitation; registry; valves ID END-POINT DEFINITIONS; CONSENSUS DOCUMENT; THORACIC SURGEONS; AORTIC-STENOSIS; IMPLANTATION; OUTCOMES; SOCIETY; LINKING AB The Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC) transcatheter valve therapy (TVT) registry is a novel, national registry for all new TVT devices created through a partnership of the STS and the ACC in close collaboration with the Food and Drug Administration, the Center for Medicare and Medicaid Services, and the Duke Clinical Research Institute. The registry will serve as an objective, comprehensive, and scientifically based resource to improve the quality of patient care, to monitor the safety and effectiveness of TVT devices, to serve as an analytic resource for TVT research, and to enhance communication among key stakeholders. (C) 2013 by the American College of Cardiology Foundation C1 [Carroll, John D.; Grover, Frederick L.] Univ Colorado, Sch Med, Aurora, CO USA. [Edwards, Fred H.] Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. [Marinac-Dabic, Danica] US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, Washington, DC 20204 USA. [Brindis, Ralph G.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Tuzcu, E. Murat] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rumsfeld, John S.] Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 USA. [Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA. [Hewitt, Kathleen] Amer Coll Cardiol Fdn, Natl Cardiovasc Data Registry, Washington, DC USA. [Holmes, David R., Jr.] Mayo Clin, Rochester, MN USA. [Mack, Michael J.] Med City Hosp, Dallas, TX USA. RP Carroll, JD (reprint author), Univ Colorado Denver, Anschutz Med Campus,Leprino Bldg,12401 East 17th, Aurora, CO 80045 USA. EM john.carroll@ucdenver.edu FU Edwards Lifesciences; Eli Lilly; Janssen Pharmaceuticals; Pfizer; Boehringer Ingleheim FX Dr. Carroll is an investigator for the PARTNER II clinical trial sponsored by Edwards Lifesciences; and a consultant to the Steering Committee of the RESPECT trial of St. Jude Medical. Dr. Marinac-Dabic is director of the Division of Epidemiology, Food and Drug Administration. Dr. Peterson receives research support from Eli Lilly, Janssen Pharmaceuticals, Pfizer, and Boehringer Ingleheim. Dr. Rumsfeld is chief science officer for the National Cardiovascular Data Registry. Dr. Shewan is a co-investigator for the ASCERT study. Dr. Mack is an uncompensated member of the executive committee of the PARTNER trial with travel expenses paid for by Edwards Lifesciences. All other authors have reported they have no relationships relevant to the contents of this paper to disclose. NR 30 TC 50 Z9 50 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 10 PY 2013 VL 62 IS 11 BP 1026 EP 1034 DI 10.1016/j.jacc.2013.03.060 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213HP UT WOS:000324046900015 PM 23644082 ER PT J AU Fuller, MJ Callendret, B Zhu, BG Freeman, GJ Hasselschwert, DL Satterfield, W Sharpe, AH Dustin, LB Rice, CM Grakoui, A Ahmed, R Walker, CM AF Fuller, Michael J. Callendret, Benoit Zhu, Baogong Freeman, Gordon J. Hasselschwert, Dana L. Satterfield, William Sharpe, Arlene H. Dustin, Lynn B. Rice, Charles M. Grakoui, Arash Ahmed, Rafi Walker, Christopher M. TI Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CD4(+) T-CELLS; IMMUNE EVASION; IN-VIVO; HCV; PERSISTENCE; CHIMPANZEES; ACTIVATION; RESPONSES; BLOCKADE; ESCAPE AB Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells that express the inhibitory receptor programmed cell death 1 (PD-1). Blockade of PD-1 signaling improves in vitro proliferation of HCV-specific T lymphocytes, but whether antiviral function can be restored in infected individuals is unknown. To address this question, chimpanzees with persistent HCV infection were treated with anti-PD-1 antibodies. A significant reduction in HCV viremia was observed in one of three treated animals without apparent hepatocellular injury. Viremia rebounded in the responder animal when antibody treatment was discontinued. Control of HCV replication was associated with restoration of intrahepatic CD4+ and CD8+ T-cell immunity against multiple HCV proteins. The responder animal had a history of broader T-cell immunity to multiple HCV proteins than the two chimpanzees that did not respond to PD-1 therapy. The results suggest that successful PD-1 blockade likely requires a critical threshold of preexisting virus-specific T cells in liver and warrants consideration of therapeutic vaccination strategies in combination with PD-1 blockade to broaden narrow responses. Anti-PD-1 immunotherapy may also facilitate control of other persistent viruses, notably the hepatitis B virus where options for long-term control of virus replication are limited. C1 [Fuller, Michael J.; Callendret, Benoit; Walker, Christopher M.] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Columbus, OH 43205 USA. [Zhu, Baogong; Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hasselschwert, Dana L.] Univ Louisiana Lafayette, New Iberia Res Ctr, New Iberia, LA 70560 USA. [Satterfield, William] MD Anderson Canc Ctr, Michale E Keeling Ctr Comparat Med & Res, Dept Vet Sci, Bastrop, TX 78602 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Dustin, Lynn B.; Rice, Charles M.] Rockefeller Univ, Lab Virol & Infect Dis, Ctr Study Hepatitis C, New York, NY 10065 USA. [Grakoui, Arash; Ahmed, Rafi] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA. [Walker, Christopher M.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. RP Ahmed, R (reprint author), Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA. EM rahmed@emory.edu; christopher.walker@nationwidechildrens.org RI Dustin, Lynn/G-5690-2011 OI Dustin, Lynn/0000-0002-2619-1867 FU Gates Foundation; US Public Health Service (USPHS) [AI070101, DK083356]; National Institutes of Health [R37 AI47367, U19 AI48231, P01 AI080192, U19 AI082630, P01 AI056299, R01 AI074417]; Yerkes Research Center [RR-00165]; New Iberia Research Center [9U42 OD014838]; American Cancer Society FX This work was supported by grants from the Gates Foundation (to R.A.) and the US Public Health Service (USPHS) and National Institutes of Health [R37 AI47367 and U19 AI48231 (to C.M.W.) and P01 AI080192, U19 AI082630, P01 AI056299, and R01 AI074417 (to G.J.F.)]. This work was also supported by USPHS Grants AI070101 and DK083356 and Yerkes Research Center Base Grant RR-00165 (to A.G.) and the New Iberia Research Center (9U42 OD014838). M.J.F. was funded in part by a postdoctoral fellowship from the American Cancer Society. NR 36 TC 58 Z9 66 U1 1 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 10 PY 2013 VL 110 IS 37 BP 15001 EP 15006 DI 10.1073/pnas.1312772110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 214IF UT WOS:000324125100048 PM 23980172 ER PT J AU Bhat, KPL Balasubramaniyan, V Vaillant, B Ezhilarasan, R Hummelink, K Hollingsworth, F Wani, K Heathcock, L James, JD Goodman, LD Conroy, S Long, LH Lelic, N Wang, SZ Gumin, J Raj, D Kodama, Y Raghunathan, A Olar, A Joshi, K Pelloski, CE Heimberger, A Kim, SH Cahill, DP Rao, G Den Dunnen, WFA Boddeke, HWGM Phillips, HS Nakano, L Lang, FF Colman, H Sulman, EP Aldape, K AF Bhat, Krishna P. L. Balasubramaniyan, Veerakumar Vaillant, Brian Ezhilarasan, Ravesanker Hummelink, Karlijn Hollingsworth, Faith Wani, Khalida Heathcock, Lindsey James, Johanna D. Goodman, Lindsey D. Conroy, Siobhan Long, Lihong Lelic, Nina Wang, Suzhen Gumin, Joy Raj, Divya Kodama, Yoshinori Raghunathan, Aditya Olar, Adriana Joshi, Kaushal Pelloski, Christopher E. Heimberger, Amy Kim, Se Hoon Cahill, Daniel P. Rao, Ganesh Den Dunnen, Wilfred F. A. Boddeke, Hendrikus W. G. M. Phillips, Heidi S. Nakano, Ichiro Lang, Frederick F. Colman, Howard Sulman, Erik P. Aldape, Kenneth TI Mesenchymal Differentiation Mediated by NF-kappa B Promotes Radiation Resistance in Glioblastoma SO CANCER CELL LA English DT Article ID STEM-CELLS; INITIATING CELLS; TUMOR MICROENVIRONMENT; MALIGNANT GLIOMA; BRAIN-TUMORS; CANCER; EXPRESSION; HETEROGENEITY; MODULATION; SENESCENCE AB Despite extensive study, few therapeutic targets have been identified for glioblastoma (GBM). Here we show that patient-derived glioma sphere cultures (GSCs) that resemble either the proneural (PN) or nnesenchymal (MES) transcriptomal subtypes differ significantly in their biological characteristics. Moreover, we found that a subset of the PN GSCs undergoes differentiation to a MES state in a TNF-alpha/NF-kappa B-dependent manner with an associated enrichment of CD44 subpopulations and radioresistant phenotypes. We present data to suggest that the tumor microenvironment cell types such as macrophages/microglia may play an integral role in this process. We further show that the MES signature, CD44 expression, and NF-kappa B activation correlate with poor radiation response and shorter survival in patients with GBM. C1 [Bhat, Krishna P. L.; Hummelink, Karlijn; Hollingsworth, Faith; Wani, Khalida; Heathcock, Lindsey; James, Johanna D.; Long, Lihong; Olar, Adriana; Aldape, Kenneth] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Ezhilarasan, Ravesanker; Goodman, Lindsey D.; Sulman, Erik P.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Wang, Suzhen] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Gumin, Joy; Heimberger, Amy; Rao, Ganesh; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Balasubramaniyan, Veerakumar; Raj, Divya; Boddeke, Hendrikus W. G. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Neurosci, NL-9713 AV Groningen, Netherlands. [Conroy, Siobhan; Den Dunnen, Wilfred F. A.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 AV Groningen, Netherlands. [Vaillant, Brian] Seton Brain & Spine Inst, Dept Neurol, Austin, TX 78701 USA. [Lelic, Nina; Cahill, Daniel P.] Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurosurg, Boston, MA 02114 USA. [Kodama, Yoshinori] Natl Hosp Org, Osaka Natl Hosp, Div Pathol, Chuo Ku, Osaka 5400006, Japan. [Raghunathan, Aditya] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA. [Joshi, Kaushal; Nakano, Ichiro] Ohio State Univ, Dept Neurosurg, Columbus, OH 43210 USA. [Pelloski, Christopher E.] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 USA. [Kim, Se Hoon] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea. [Phillips, Heidi S.] Genentech Inc, Dept Tumor Biol & Angiogenesis, San Francisco, CA 94080 USA. [Colman, Howard] Univ Utah, Dept Neurosurg, Salt Lake City, UT 84132 USA. [Colman, Howard] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84132 USA. RP Bhat, KPL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. EM kbhat@mdanderson.org; epsulman@mdanderson.org; kaldape@mdanderson.org RI den Dunnen, Wilfred/A-4034-2009 FU Caroline Ross Endowment Fellowship; American Brain Tumor Association Basic Research Fellowship; Odyssey Special Fellowship; MDACC Brain Tumor SPORE Career Development grant; Brain Tumor Funders' Collaborative; Dr. Marnie Rose Foundation; National Brain Tumor Society; V Foundation; NIH/NCI [P50CA127001, R01-CA1208113]; Huntsman Cancer Foundation; Ben and Cathy Ivy Foundation Research Award; SPORE Animal Core grant; Dutch Cancer Society [RUG 2011-5150] FX We would like to acknowledge the Caroline Ross Endowment Fellowship, the American Brain Tumor Association Basic Research Fellowship, the Odyssey Special Fellowship, and the MDACC Brain Tumor SPORE Career Development grant (to K.P.L.B.); the Brain Tumor Funders' Collaborative, the Dr. Marnie Rose Foundation, and the National Brain Tumor Society (to K.A.); the V Foundation and SPORE grant P50CA127001 from NIH/NCI (to K.A. and N.C.); the Huntsman Cancer Foundation (to H.C.); the Ben and Cathy Ivy Foundation Research Award (to F.F.L., K.A., and E.P.S.); the SPORE Animal Core grant (to F.F.L.); grant R01-CA1208113 from NIH/NCI (to A.H.); and Dutch Cancer Society grant RUG 2011-5150 (to V.B., H.W.B., and W.F.D.) for their generous support. We thank Alicia Ledoux, Bhavna Singh, and Susan Cweren for histology; Verlene Henry for animal injections; and the Flow Cytometry & Cellular Imaging Core Facility, Small Animal Imaging Facility, and the Division of Surgery Pathology Core Facility (all at MDACC supported by P30-CA016672) for technical support. We apologize for not citing some original references because of space limitations. H.S.P. is an employee and stockholder of Roche/Genentech. NR 54 TC 170 Z9 174 U1 0 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD SEP 9 PY 2013 VL 24 IS 3 BP 331 EP 346 DI 10.1016/j.ccr.2013.08.001 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 251DN UT WOS:000326908100012 PM 23993863 ER PT J AU Tam, WL Lu, HH Buikhuisen, J Soh, BS Lim, E Reinhardt, F Wu, ZJ Krall, JA Bierie, B Guo, WJ Chen, X Liu, XS Brown, M Lim, B Weinberg, RA AF Tam, Wai Leong Lu, Haihui Buikhuisen, Joyce Soh, Boon Seng Lim, Elgene Reinhardt, Ferenc Wu, Zhenhua Jeremy Krall, Jordan A. Bierie, Brian Guo, Wenjun Chen, Xi Liu, Xiaole Shirley Brown, Myles Lim, Bing Weinberg, Robert A. TI Protein Kinase C alpha Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells SO CANCER CELL LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; FACTOR RECEPTOR INHIBITION; GROWTH-FACTOR; PHOSPHORYLATION; DISEASE; LINES; HETEROGENEITY; FIBROBLASTS; DETERMINANT; SENSITIVITY AB The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C alpha (PKC alpha) specifically targets CSCs but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling and results in the PKC alpha-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKC alpha and FRA1 expression is associated with the aggressive triple-negative breast cancers, and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs. C1 [Tam, Wai Leong; Lu, Haihui; Buikhuisen, Joyce; Reinhardt, Ferenc; Krall, Jordan A.; Bierie, Brian; Weinberg, Robert A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Soh, Boon Seng; Lim, Bing] Genome Inst Singapore, Singapore 138672, Singapore. [Lim, Elgene; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Zhenhua Jeremy; Liu, Xiaole Shirley] Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA. [Wu, Zhenhua Jeremy; Liu, Xiaole Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Guo, Wenjun] Albert Einstein Coll Med, Gottesman Inst Stem Cell & Regenerat Med Res, Bronx, NY 10461 USA. [Chen, Xi] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Weinberg, Robert A.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Weinberg, Robert A.] MIT, Ludwig Ctr Mol Oncol, Cambridge, MA 02139 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu OI Chen, Xi/0000-0002-7995-6202; Lim, Elgene/0000-0001-8065-8838; Brown, Myles/0000-0002-8213-1658; Tam, Wai Leong/0000-0003-2365-5264 FU Breast Cancer Research Foundation; National Cancer Institute Program [P01-CA080111]; National Institutes of Health [R01-CA078461]; MIT Ludwig Center for Molecular Oncology; Agency for Science, Technology and Research (Singapore) FX We thank Tsukasa Shibue for helpful comments and Tom DiCesare for illustrations. This research was supported by grants from the Breast Cancer Research Foundation, National Cancer Institute Program (P01-CA080111), and National Institutes of Health (R01-CA078461). R.A.W. is an American Cancer Society and Ludwig Foundation professor. W.L.T. is supported by the MIT Ludwig Center for Molecular Oncology and the Agency for Science, Technology and Research (Singapore). NR 38 TC 89 Z9 90 U1 4 U2 30 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD SEP 9 PY 2013 VL 24 IS 3 BP 347 EP 364 DI 10.1016/j.ccr.2013.08.005 PG 18 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 251DN UT WOS:000326908100013 PM 24029232 ER PT J AU McLaughlin, SK Olsen, SN Dake, B De Raedt, T Lim, E Bronson, RT Beroukhim, R Polyak, K Brown, M Kuperwasser, C Cichowski, K AF McLaughlin, Sara Koenig Olsen, Sarah Naomi Dake, Benjamin De Raedt, Thomas Lim, Elgene Bronson, Roderick Terry Beroukhim, Rameen Polyak, Kornelia Brown, Myles Kuperwasser, Charlotte Cichowski, Karen TI The RasGAP Gene, RASAL2, Is a Tumor and Metastasis Suppressor SO CANCER CELL LA English DT Article ID HUMAN BREAST-CANCER; ACTIVATED PROTEIN-KINASE; MOLECULAR PORTRAITS; SOMATIC MUTATIONS; IN-SITU; DISEASE; EXPRESSION; PATHWAYS; MODELS; MICE AB RAS genes are commonly mutated in cancer; however, RAS mutations are rare in breast cancer, despite frequent hyperactivation of Ras and ERK. Here, we report that the RasGAP gene, RASAL2, functions as a tumor and metastasis suppressor. RASAL2 is mutated or suppressed in human breast cancer, and RASAL2 ablation promotes tumor growth, progression, and metastasis in mouse models. In human breast cancer, RASAL2 loss is associated with metastatic disease; low RASAL2 levels correlate with recurrence of lumina! B tumors; and RASAL2 ablation promotes metastasis of luminal mouse tumors. Additional data reveal a broader role for RASAL2 inactivation in other tumor types. These studies highlight the expanding role of RasGAPs and reveal an alternative mechanism of activating Ras in cancer. C1 [McLaughlin, Sara Koenig; Olsen, Sarah Naomi; De Raedt, Thomas; Cichowski, Karen] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [McLaughlin, Sara Koenig; Olsen, Sarah Naomi; De Raedt, Thomas; Lim, Elgene; Beroukhim, Rameen; Polyak, Kornelia; Brown, Myles; Cichowski, Karen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [McLaughlin, Sara Koenig; Olsen, Sarah Naomi; De Raedt, Thomas; Lim, Elgene; Bronson, Roderick Terry; Beroukhim, Rameen; Polyak, Kornelia; Brown, Myles; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dake, Benjamin; Kuperwasser, Charlotte] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Dev Mol & Biochem Biol, Boston, MA 02111 USA. [Dake, Benjamin; Kuperwasser, Charlotte] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Lim, Elgene; Polyak, Kornelia; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Beroukhim, Rameen] MIT, Broad Inst, Cambridge, MA 02142 USA. [Beroukhim, Rameen] Harvard Univ, Cambridge, MA 02142 USA. [De Raedt, Thomas; Cichowski, Karen] Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA 02115 USA. RP Cichowski, K (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu OI Lim, Elgene/0000-0001-8065-8838; Brown, Myles/0000-0002-8213-1658 FU Ludwig Center at Dana-Farber/Harvard Cancer Center; National Cancer Institute [R01 CA111754]; Department of Defense [W81XWH-11-1-0140]; National Institutes of Health National Heart, Lung, and Blood Institute [T32-HL07623] FX This work was supported by grants from the Ludwig Center at Dana-Farber/Harvard Cancer Center (to K.C.), the National Cancer Institute (R01 CA111754 to K.C.), the Department of Defense (W81XWH-11-1-0140 to S.K.M.), and the National Institutes of Health National Heart, Lung, and Blood Institute (T32-HL07623 to S.K.M.). NR 43 TC 35 Z9 39 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD SEP 9 PY 2013 VL 24 IS 3 BP 365 EP 378 DI 10.1016/j.ccr.2013.08.004 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 251DN UT WOS:000326908100014 PM 24029233 ER PT J AU Korrapati, MC Howell, LH Shaner, BE Megyesi, JK Siskind, LJ Schnellmann, RG AF Korrapati, Midhun C. Howell, Lauren H. Shaner, Brooke E. Megyesi, Judit K. Siskind, Leah J. Schnellmann, Rick G. TI Suramin: A Potential Therapy for Diabetic Nephropathy SO PLOS ONE LA English DT Article ID TUBULAR EPITHELIAL-CELLS; KAPPA-B ACTIVATION; KIDNEY-DISEASE; RENAL INJURY; DB/DB MOUSE; TGF-BETA; FIBROSIS; MECHANISMS; RATS; MICE AB Objective: To determine whether delayed administration of a single dose of suramin, a drug that has been used extensively in humans to treat trypanosomiasis, attenuates renal injury in a leptin receptor deficient C57BLKS/J db/db type 2 diabetic nephropathy (T2DN) mouse model. Research Design and Methods: Groups of female non-diabetic (control) db/m and diabetic db/db mice of 8 and 16 weeks of age, respectively, were treated with suramin (10 mg/kg) or saline i.v. All animals were euthanized one week later. Measurements in mice 1 week following treatment included the following: body weight; blood glucose; urinary protein excretion; pathological lesions in glomeruli and proximal tubules; changes in protein expression of pro-inflammatory transcription factor nuclear factor kappa B (NF-kappa B) and intracellular adhesion molecule-1 (ICAM-1), profibrotic transforming growth factor-beta 1 (TGF-beta 1), phospho-SMAD-3 and alpha-smooth muscle actin (alpha-SMA); and immunohistochemical analysis of leukocyte infiltration and collagen 1A2 (COL1A2) deposition. Results: Immunoblot analysis revealed increased NF-kappa B, ICAM-1, TGF-beta 1, phospho-SMAD-3, and alpha-SMA proteins in both 9 and 17 week db/db mice as compared to db/m control mice. Immunohistochemical analysis revealed moderate leukocyte infiltration and collagen 1A2 (COL1A2) deposition in 9 week db/db mice that was increased in the 17 week db/db mice. Importantly, suramin significantly decreased expression of all these markers in 9 week db/db mice and partially decreased in 17 week db/db mice without altering body weight, blood glucose or urinary protein excretion. There was no difference in creatinine clearance between 9 week db/m and db/db mice +/- suramin. Importantly, in the 17 week db/db mice suramin intervention reversed the impaired creatinine clearance and overt histological damage. Conclusions: Delayed administration of a single dose of suramin in a model of T2DN attenuated inflammation and fibrosis as well as improved renal function, supporting the use of suramin in T2DN. C1 [Korrapati, Midhun C.; Howell, Lauren H.; Shaner, Brooke E.; Siskind, Leah J.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Megyesi, Judit K.] Univ Arkansas Med Sci, Div Nephrol, Coll Med, Dept Internal Med, Little Rock, AR 72205 USA. [Siskind, Leah J.; Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Siskind, LJ (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. EM leah.siskind@louisville.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01DK093462]; Cancer Center Support Grant [P30 CA138313]; Centers of Biomedical Research Excellence in Lipidomics and Pathobiology [NIH/NCRR P20 RR17677]; South Carolina Centers of Biomedical Research Excellence in Oxidants, Redox Balance and Stress Signaling [P20 GM103542]; National Institutes of Health [GM 084147, C06 RR-015455]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; South Carolina Clinical & Translational Research (SCTR) Institute; Medical University of South Carolina CTSA, NIH/NCRR [UL1RR029882] FX Research reported in this publication was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, [R01DK093462] (to L.J.S.), the Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina supported by a Cancer Center Support Grant [P30 CA138313], pilot project from the [NIH/NCRR P20 RR17677] Centers of Biomedical Research Excellence in Lipidomics and Pathobiology (to L.J.S), South Carolina Centers of Biomedical Research Excellence in Oxidants, Redox Balance and Stress Signaling [P20 GM103542], pilot project from the [NIH/NCRR P20 RR17677], National Institutes of Health Grant [GM 084147] and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by National Institutes of Health grant [C06 RR-015455]. This reseach was supported in part by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina CTSA, NIH/NCRR Grant Number UL1RR029882. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, VA, or National Center for Research Resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 8 Z9 8 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 9 PY 2013 VL 8 IS 9 AR e73655 DI 10.1371/journal.pone.0073655 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 244QV UT WOS:000326405300104 PM 24040012 ER PT J AU Horowitz, SH AF Horowitz, Steven H. TI Diagnostic Decision-Making, Burdens of Proof, and a $6000 per Hour Memory Lapse SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID TRANSIENT GLOBAL AMNESIA C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Horowitz, SH (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 835,55 Fruit St, Boston, MA 02114 USA. EM shhorowitz@partners.org NR 10 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP 9 PY 2013 VL 173 IS 16 BP 1493 EP 1494 DI 10.1001/jamainternmed.2013.8409 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 218VS UT WOS:000324461200003 PM 23836160 ER PT J AU Lam, KD Miao, YH Steinman, MA AF Lam, Khoa D. Miao, Yinghui Steinman, Michael A. TI Cumulative Changes in the Use of Long-term Medications: A Measure of Prescribing Complexity SO JAMA INTERNAL MEDICINE LA English DT Letter ID REGIMEN C1 [Lam, Khoa D.; Steinman, Michael A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Lam, Khoa D.; Miao, Yinghui; Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Miao, Yinghui; Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,POB 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [K23 AG030999, RC1 AG036377, RC1-AG036377, 1K23-AG030999, P30 AG044281] NR 5 TC 3 Z9 3 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP 9 PY 2013 VL 173 IS 16 BP 1546 EP 1547 DI 10.1001/jamainternmed.2013.7060 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 218VS UT WOS:000324461200015 PM 23752793 ER PT J AU Bodhankar, S Chen, YX Vandenbark, AA Murphy, SJ Offner, H AF Bodhankar, Sheetal Chen, Yingxin Vandenbark, Arthur A. Murphy, Stephanie J. Offner, Halina TI PD-L1 enhances CNS inflammation and infarct volume following experimental stroke in mice in opposition to PD-1 SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Co-inhibitory pathway; Inflammatory states; MCAO; Programmed death-1 ligand 1 and 2 ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ISCHEMIC-STROKE; PERIPHERAL TOLERANCE; DEFICIENT MICE; EXPRESSION; RESPONSES; LIGANDS; PATHWAY; IMMUNITY AB Background: Stroke severity is worsened by recruitment of inflammatory immune cells into the brain. This process depends in part on T cell activation, in which the B7 family of co-stimulatory molecules plays a pivotal role. Previous studies demonstrated more severe infarcts in mice lacking programmed death-1 (PD-1), a member of the B7 family, thus implicating PD-1 as a key factor in limiting stroke severity. The purpose of this study was to determine if this protective effect of PD-1 involves either of its ligands, PD-L1 or PD-L2. Methods: Central nervous system (CNS) inflammation and infarct volume were evaluated in male PD-L1 and PD-L2 knockout ((-/-)) mice undergoing 60 minutes of middle cerebral artery occlusion (MCAO) followed by 96 hours of reperfusion and compared to wild-type (WT) C57BL/6J mice. Results: PD-L1(-/-) and PD-L2(-/-) mice had smaller total infarct volumes compared to WT mice. The PD-L1-/-and to a lesser extent PD-L2(-/-) mice had reduced levels of proinflammatory activated microglia and/or infiltrating monocytes and CD4(+) T cells in the ischemic hemispheres. There was a reduction in ischemia-related splenic atrophy accompanied by lower activation status of splenic T cells and monocytes in the absence of PD-L1, suggesting a pathogenic rather than a regulatory role for both PD-1 ligands (PD-Ls). Suppressor T cells (IL-10-producing CD8(+) CD122(+) T cells) trafficked to the brain in PD-L1(-/-) mice and there was decreased expression of CD80 on splenic antigen-presenting cells (APCs) as compared to the WT and PD-L2(-/-) mice. Conclusions: Our novel observations are the first to implicate PD-L1 involvement in worsening outcome of experimental stroke. The presence of suppressor T cells in the right MCAO-inflicted hemisphere in mice lacking PDL1 implicates these cells as possible key contributors for controlling adverse effects of ischemia. Increased expression of CD80 on APCs in WT and PD-L2(-/-) mice suggests an overriding interaction leading to T cell activation. Conversely, low CD80 expression by APCs, along with increased PD-1 and PD-L2 expression in PD-L1(-/-) mice suggests alternative T cell signaling pathways, leading to a suppressor phenotype. These results suggest that agents (for example antibodies) that can target and neutralize PD-L1/2 may have therapeutic potential for treatment of human stroke. C1 [Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, R&D 31, Portland, OR 97239 USA. [Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Chen, Yingxin; Murphy, Stephanie J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Murphy, Stephanie J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH/National Institute of Neurological Disorders and Stroke (NINDS) [1RO1 NS075887]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; Biomedical Laboratory Research and Development FX The authors wish to thank Melissa Barber for assistance with manuscript submission. This work was supported by NIH/National Institute of Neurological Disorders and Stroke (NINDS): 1RO1 NS075887. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 47 TC 21 Z9 21 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD SEP 9 PY 2013 VL 10 AR 111 DI 10.1186/1742-2094-10-111 PG 15 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 214OL UT WOS:000324143300001 PM 24015822 ER PT J AU Tiyanont, K Wales, TE Siebel, CW Engen, JR Blacklow, SC AF Tiyanont, Kittichoat Wales, Thomas E. Siebel, Christian W. Engen, John R. Blacklow, Stephen C. TI Insights into Notch3 Activation and Inhibition Mediated by Antibodies Directed against Its Negative Regulatory Region SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE signal transduction; Notch signaling; autoinhibition; hydrogen exchange-mass spectrometry; regulated intramembrane proteolysis ID SQUAMOUS-CELL CARCINOMA; PROTEOLYTIC ACTIVATION; ALAGILLE-SYNDROME; MUTATIONS; CLEAVAGE; RECEPTORS; LIGAND; DOMAIN; REPEATS; PATHWAY AB Notch receptors are single-pass transmembrane proteins that regulate development and tissue homeostasis in all metazoan organisms. Prior to ligand-induced signaling, Notch receptors adopt a proteolytic resistant conformation maintained by a critical interdomain interface within a negative regulatory region (NRR), which sits immediately external to the plasma membrane. Signaling is initiated when ligand binding induces exposure of the proteolytic cleavage site, termed S2, within the NRR. Here, we use hydrogen exchange in conjunction with mass spectrometry to study the dynamics of the human Notch3 NRR in four distinct biochemical states: in its unmodified quiescent form, in a proteolytically "on" state induced by ethylenediaminetetraacetic acid, and in complex with either agonist or inhibitory antibodies. Induction of the on state by either ethylenediaminetetraacetic acid or the agonist monoclonal antibody leads to accelerated deuteration in the region of the S2 cleavage site, reflecting an increase in S2 dynamics. In contrast, complexation of the Notch3 NRR with an inhibitory antibody retards deuteration not only across its discontinuous binding epitope but also around the S2 site, stabilizing the NRR in its "off" state. Together with previous work investigating the dynamics of the Notch1 NRR, these studies show that key features of autoinhibition and activation are shared among different Notch receptors and provide additional insights into mechanisms of Notch activation and inhibition by modulatory antibodies. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Tiyanont, Kittichoat; Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tiyanont, Kittichoat; Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Wales, Thomas E.; Engen, John R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Siebel, Christian W.] Genentech Inc, Div Res, Dept Mol Biol, San Francisco, CA 94080 USA. [Blacklow, Stephen C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Blacklow, Stephen C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Blacklow, SC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM Stephen_blacklow@hms.harvard.edu FU National Institutes of Health [R01 CA092433, GM086507, GM101135]; Waters Corporation FX This work is supported by National Institutes of Health grant R01 CA092433 (to S.C.B.), National Institutes of Health awards GM086507 and GM101135 (to J.R.E.), and a research collaboration with the Waters Corporation. We thank Wendy Gordon, Jon Aster, and Roxana Iacob for helpful discussions. NR 39 TC 7 Z9 8 U1 1 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 9 PY 2013 VL 425 IS 17 BP 3192 EP 3204 DI 10.1016/j.jmb.2013.05.025 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210UN UT WOS:000323860300013 PM 23747483 ER PT J AU Aldrich, L Castoreno, A Kuo, SY Dancik, V Goel, G Kuballa, P Shamji, A Xavier, R Schreiber, S AF Aldrich, Leslie Castoreno, Adam Kuo, Szu-Yu Dancik, Vlado Goel, Gautam Kuballa, Petric Shamji, Alykhan Xavier, Ramnik Schreiber, Stuart TI Development of small-molecule autophagy modulators for the study of Crohn's disease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 246th National Meeting of the American-Chemical-Society (ACS) CY SEP 08-12, 2013 CL Indianapolis, IN SP Amer Chem Soc C1 [Aldrich, Leslie; Schreiber, Stuart] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Aldrich, Leslie; Castoreno, Adam; Kuo, Szu-Yu; Dancik, Vlado; Goel, Gautam; Kuballa, Petric; Shamji, Alykhan; Xavier, Ramnik; Schreiber, Stuart] Broad Inst, Chem Biol Program, Cambridge, MA USA. [Castoreno, Adam; Goel, Gautam; Kuballa, Petric; Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Kuo, Szu-Yu] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Gastrointenstinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. EM laldrich@fas.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 8 PY 2013 VL 246 MA 255-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 288NJ UT WOS:000329618405008 ER PT J AU Haggarty, S AF Haggarty, Stephen TI Targeting epigenetic mechanisms involved in neuroplasticity and memory SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 246th National Meeting of the American-Chemical-Society (ACS) CY SEP 08-12, 2013 CL Indianapolis, IN SP Amer Chem Soc C1 [Haggarty, Stephen] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Haggarty, Stephen] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM haggarty@chgr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP 8 PY 2013 VL 246 MA 28-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 288NJ UT WOS:000329618404689 ER PT J AU Lane, KJ Scammell, MK Levy, JI Fuller, CH Parambi, R Zamore, W Mwamburi, M Brugge, D AF Lane, Kevin J. Scammell, Madeleine Kangsen Levy, Jonathan I. Fuller, Christina H. Parambi, Ron Zamore, Wig Mwamburi, Mkaya Brugge, Doug TI Positional error and time-activity patterns in near-highway proximity studies: an exposure misclassification analysis SO ENVIRONMENTAL HEALTH LA English DT Article DE Highway proximity; Time-activity; Traffic; Geocoding; Exposure misclassification ID AIR-POLLUTION; ULTRAFINE PARTICLES; PERSONAL EXPOSURE; BLACK CARBON; QUALITY; MODELS; POLLUTANTS; REGRESSION; CHILDREN; MOBILITY AB Background: The growing interest in research on the health effects of near-highway air pollutants requires an assessment of potential sources of error in exposure assignment techniques that rely on residential proximity to roadways. Methods: We compared the amount of positional error in the geocoding process for three different data sources (parcels, TIGER and StreetMap USA) to a "gold standard" residential geocoding process that used ortho-photos, large multi-building parcel layouts or large multi-unit building floor plans. The potential effect of positional error for each geocoding method was assessed as part of a proximity to highway epidemiological study in the Boston area, using all participants with complete address information (N = 703). Hourly time-activity data for the most recent workday/weekday and non-workday/weekend were collected to examine time spent in five different microenvironments (inside of home, outside of home, school/work, travel on highway, and other). Analysis included examination of whether time-activity patterns were differentially distributed either by proximity to highway or across demographic groups. Results: Median positional error was significantly higher in street network geocoding (StreetMap USA = 23 m; TIGER = 22 m) than parcel geocoding (8 m). When restricted to multi-building parcels and large multi-unit building parcels, all three geocoding methods had substantial positional error (parcels = 24 m; StreetMap USA = 28 m; TIGER = 37 m). Street network geocoding also differentially introduced greater amounts of positional error in the proximity to highway study in the 0-50 m proximity category. Time spent inside home on workdays/weekdays differed significantly by demographic variables (age, employment status, educational attainment, income and race). Time-activity patterns were also significantly different when stratified by proximity to highway, with those participants residing in the 0-50 m proximity category reporting significantly more time in the school/work micro-environment on workdays/weekdays than all other distance groups. Conclusions: These findings indicate the potential for both differential and non-differential exposure misclassification due to geocoding error and time-activity patterns in studies of highway proximity. We also propose a multi-stage manual correction process to minimize positional error. Additional research is needed in other populations and geographic settings. C1 [Lane, Kevin J.; Scammell, Madeleine Kangsen; Levy, Jonathan I.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Fuller, Christina H.] Georgia State Univ, Inst Publ Hlth, Atlanta, GA 30303 USA. [Parambi, Ron] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Zamore, Wig] Somerville Transportat Equ Partnership, Somerville, MA USA. [Mwamburi, Mkaya; Brugge, Doug] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Lane, KJ (reprint author), Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. EM KLane@BU.edu RI Levy, Jon/B-4542-2011 OI Levy, Jon/0000-0002-1116-4006 FU National Institute of Environmental Health Sciences [ES015462]; EPA STAR Fellowship [FP-917349-01-0]; STAR Fellowship [FP-917349-01-0]; U.S. Environmental Protection Agency (EPA) FX We would like to thank the members of the CAFEH Steering Committee: Ellin Reisner, John Durant, Baolian Kuang, Lydia Lowe, Edna Carrasco, M. Barton Laws, Yuping Zeng, Emmanuel Owusu, Mae Fripp, Tina Wang, Michelle Liang, and Mario Davia. We also acknowledge the great help from our community partners the Chinatown Progressive Association (CPA) and Somerville Transportation Equity Partnership (STEP) for assisting us in obtaining the apartment building and parcel layout plans. We thank our project manager Don Meglio and his field team: Kevin Stone, Marie Manis, Consuelo Perez, Marjorie Alexander, Maria Crispin, Reva Levin, Helene Sroat, Carmen Rodriguez, Migdalia Tracy, Sidia Escobar, Kim-Lien Le, Stephanie Saintil, Robert Baptiste, Joseph Penella, Lisa Ng, Vladimir Albin Jr., Janet Vo, Quynh Dam, Lin Yian, Betsey Rodman, Marie Echevarria, and Barbara Anderson for their dedication and hard work. Funding was provided by the National Institute of Environmental Health Sciences (ES015462). Support for Lane was provided by an EPA STAR Fellowship (FP-917349-01-0). This publication was developed under STAR Fellowship Assistance Agreement no. FP-917349-01-0 awarded by the U.S. Environmental Protection Agency (EPA). It has not been formally reviewed by EPA. The views expressed in this publication are solely those of Kevin Lane, and EPA does not endorse any products or commercial services mentioned in this publication. NR 31 TC 9 Z9 9 U1 3 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD SEP 8 PY 2013 VL 12 AR 75 DI 10.1186/1476-069X-12-75 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 242YL UT WOS:000326282500001 PM 24010639 ER PT J AU Yarmand, H Winey, B Craft, D AF Yarmand, Hamed Winey, Brian Craft, David TI Guaranteed epsilon-optimal treatment plans with the minimum number of beams for stereotactic body radiation therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RECTANGULAR APERTURES; ANGLE OPTIMIZATION; MAP OPTIMIZATION; RADIOTHERAPY AB Stereotactic body radiation therapy (SBRT) is characterized by delivering a high amount of dose in a short period of time. In SBRT the dose is delivered using open fields (e.g., beam's-eye-view) known as 'apertures'. Mathematical methods can be used for optimizing treatment planning for delivery of sufficient dose to the cancerous cells while keeping the dose to surrounding organs at risk (OARs) minimal. Two important elements of a treatment plan are quality and delivery time. Quality of a plan is measured based on the target coverage and dose to OARs. Delivery time heavily depends on the number of beams used in the plan as the setup times for different beam directions constitute a large portion of the delivery time. Therefore the ideal plan, in which all potential beams can be used, will be associated with a long impractical delivery time. We use the dose to OARs in the ideal plan to find the plan with the minimum number of beams which is guaranteed to be epsilon-optimal (i.e., a predetermined maximum deviation from the ideal plan is guaranteed). Since the treatment plan optimization is inherently a multi-criteria-optimization problem, the planner can navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus OARs sparing, and then use the proposed technique to reduce the number of beams while guaranteeing epsilon-optimality. We use mixed integer programming (MIP) for optimization. To reduce the computation time for the resultant MIP, we use two heuristics: a beam elimination scheme and a family of heuristic cuts, known as 'neighbor cuts', based on the concept of 'adjacent beams'. We show the effectiveness of the proposed technique on two clinical cases, a liver and a lung case. Based on our technique we propose an algorithm for fast generation of epsilon-optimal plans. C1 [Yarmand, Hamed] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yarmand, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM yarmand.hamed@mgh.harvard.edu FU federal share of program income earned by Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267]; RaySearch Laboratories FX This research was supported by the federal share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center, and by RaySearch Laboratories. NR 24 TC 4 Z9 4 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 7 PY 2013 VL 58 IS 17 BP 5931 EP 5944 DI 10.1088/0031-9155/58/17/5931 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 206JX UT WOS:000323517700011 PM 23920378 ER PT J AU Sun, PZ Lu, J Wu, Y Xiao, G Wu, RH AF Sun, Phillip Zhe Lu, Jie Wu, Yin Xiao, Gang Wu, Renhua TI Evaluation of the dependence of CEST-EPI measurement on repetition time, RF irradiation duty cycle and imaging flip angle for enhanced pH sensitivity SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID EXCHANGE SATURATION-TRANSFER; MAGNETIZATION-TRANSFER ASYMMETRY; CHEMICAL-EXCHANGE; IN-VIVO; TRANSFER CONTRAST; PARACEST AGENTS; 7 T; QUANTITATIVE DESCRIPTION; HUMAN BRAIN; MRI AB Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging (MRI) contrast mechanism that can detect dilute CEST agents and microenvironmental properties, with a host of promising applications. Experimental measurement of the CEST effect is complex, and depends on not only CEST agent concentration and exchange rate, but also experimental parameters such as RF irradiation amplitude and scheme. Although echo planar imaging (EPI) has been increasingly used for CEST MRI, the relationship between CEST effect and repetition time (TR), RF irradiation duty cycle (DC) and EPI flip angle (alpha) has not been fully evaluated and optimized to enhance CEST MRI sensitivity. In addition, our study evaluated gradient echo CEST-EPI by quantifying the CEST effect and its signal-to-noise ratio per unit time (SNRput) as functions of TR, DC and alpha. We found that CEST effect increased with TR and DC but decreased with alpha. Importantly, we found that SNRput peaked at intermediate TRs of about twice the T-1 and alpha, at approximately 75 degrees, and increased with RF DC. The simulation results were validated using a dual-pH creatine-gel CEST phantom. In summary, our study provides a useful framework for optimizing CEST MRI experiments. C1 [Sun, Phillip Zhe; Lu, Jie] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sun, Phillip Zhe; Lu, Jie] Harvard Univ, Sch Med, Charlestown, MA USA. [Wu, Yin] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab MRI, Paul C Lauterbur Res Ctr Biomed Imaging, Shenzhen, Peoples R China. [Xiao, Gang] Hanshan Normal Univ, Dept Math & Appl Math, Chaozhou, Peoples R China. [Wu, Renhua] Shantou Univ, Coll Med, Affiliated Hosp 2, Dept Radiol, Shantou 515063, Peoples R China. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM pzhesun@nmr.mgh.harvard.edu; rhwu@stu.edu.cn FU NIH/NIBIB [1K01EB009771]; NIH/NINDS [1R01NS083654]; NIH/NCRR [P41RR14075]; NSFC [30900365, 30930027] FX This study was supported in part by grants from NIH/NIBIB 1K01EB009771, NIH/NINDS 1R01NS083654, NIH/NCRR P41RR14075, NSFC 30900365 and 30930027. The authors would like to thank Nichole Eusemann for editorial assistance. NR 51 TC 11 Z9 12 U1 1 U2 18 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 7 PY 2013 VL 58 IS 17 BP N229 EP N240 DI 10.1088/0031-9155/58/17/N229 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 206JX UT WOS:000323517700001 PM 23939228 ER PT J AU Zhao, PS Canals, M Murphy, JE Klingler, D Eriksson, EM Pelayo, JC Hardt, M Bunnett, NW Poole, DP AF Zhao, Peishen Canals, Meritxell Murphy, Jane E. Klingler, Diana Eriksson, Emily M. Pelayo, Juan-Carlos Hardt, Markus Bunnett, Nigel W. Poole, Daniel P. TI Agonist-biased Trafficking of Somatostatin Receptor 2A in Enteric Neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; ARRESTIN; CELLS; INTERNALIZATION; ENDOSOMES; MOUSE; ENDOCYTOSIS; OCTREOTIDE; EXPRESSION; ISOFORMS AB Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with beta-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin-and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and beta-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/beta-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from beta-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained beta-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions. C1 [Zhao, Peishen; Canals, Meritxell; Bunnett, Nigel W.; Poole, Daniel P.] Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia. [Murphy, Jane E.; Pelayo, Juan-Carlos] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Klingler, Diana; Hardt, Markus] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Eriksson, Emily M.] Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA 94110 USA. RP Bunnett, NW (reprint author), Monash Inst Pharmaceut Sci, 381 Royal Parade, Parkville, Vic 3052, Australia. EM Nigel.Bunnett@Monash.edu; Daniel.Poole@Monash.edu OI Canals, Meritxell/0000-0002-7942-5006 FU NIDCR National Institutes of Health [1R01DE019796]; National Health and Medical Research Council (NHMRC) [63303, 103188]; Monash University; NHMRC [454858] FX This work was supported, in whole or in part, by NIDCR National Institutes of Health Grant 1R01DE019796 (to M. H. and N. W. B). This work was also supported by National Health and Medical Research Council (NHMRC) Grants 63303 and 103188 and Monash University (to N. W. B.) and by NHMRC Grant 454858 (to D. P. P.). NR 32 TC 10 Z9 10 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 6 PY 2013 VL 288 IS 36 BP 25689 EP 25700 DI 10.1074/jbc.M113.496414 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302RT UT WOS:000330623300003 PM 23913690 ER PT J AU Witt, RM Hecht, ML Pazyra-Murphy, MF Cohen, SM Noti, C van Kuppevelt, TH Fuller, M Chan, JA Hopwood, JJ Seeberger, PH Segal, RA AF Witt, Rochelle M. Hecht, Marie-Lyn Pazyra-Murphy, Maria F. Cohen, Samuel M. Noti, Christian van Kuppevelt, Toin H. Fuller, Maria Chan, Jennifer A. Hopwood, John J. Seeberger, Peter H. Segal, Rosalind A. TI Heparan Sulfate Proteoglycans Containing a Glypican 5 Core and 2-O-Sulfo-iduronic Acid Function as Sonic Hedgehog Co-receptors to Promote Proliferation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRIMARY CILIUM; DALLY-LIKE; INTRAFLAGELLAR TRANSPORT; CELL-PROLIFERATION; TOUT-VELU; PROTEINS; PATHWAY; BINDING; ROLES; CDO AB Sonic Hedgehog (Shh) signaling is crucial for growth, cell fate determination, and axonal guidance in the developing nervous system. Although the receptors Patched (Ptch1) and Smoothened (Smo) are required for Shh signaling, a number of distinct co-receptors contribute to these critical responses to Shh. Several membrane-embedded proteins such as Boc, Cdo, and Gas1 bind Shh and promote signaling. In addition, heparan sulfate proteoglycans (HSPGs) have also been implicated in the initiation of Shh responses. However, the attributes of HSPGs that function as co-receptors for Shh have not yet been defined. Here, we identify HSPGs containing a glypican 5 core protein and 2-O-sulfo-iduronic acid residues at the nonreducing ends of the glycans as co-receptors for Shh. These HSPG co-receptors are expressed by cerebellar granule cell precursors and promote Shh binding and signaling. At the subcellular level, these HSPG co-receptors are located adjacent to the primary cilia that act as Shh signaling organelles. Thus, Shh binds to HSPG co-receptors containing a glypican 5 core and 2-O-sulfo-iduronic acid to promote neural precursor proliferation. C1 [Witt, Rochelle M.; Pazyra-Murphy, Maria F.; Cohen, Samuel M.; Segal, Rosalind A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Witt, Rochelle M.; Pazyra-Murphy, Maria F.; Cohen, Samuel M.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02215 USA. [Hecht, Marie-Lyn; Seeberger, Peter H.] Max Planck Inst Colloids & Interfaces, D-14476 Golm, Germany. [Hecht, Marie-Lyn; Noti, Christian] Fed Inst Technol ETH Zurich, CH-8093 Zurich, Switzerland. [van Kuppevelt, Toin H.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Biochem, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. [Fuller, Maria; Hopwood, John J.] SA Pathol, Lysosomal Dis Res Unit, Womens & Childrens Hosp, Adelaide, SA 5006, Australia. [Chan, Jennifer A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 4N1, Canada. [Seeberger, Peter H.] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany. RP Seeberger, PH (reprint author), Max Planck Inst Colloids & Interfaces, Muhlenberg 1, D-14476 Golm, Germany. EM peter.seeberger@mpikg.mpg.de; Rosalind_segal@dfci.harvard.edu RI Kuppevelt, A.H.M.S.M./L-4463-2015 FU National Institutes of Health Director's Pioneer Award [DP1 0D000839]; Quan Fellowship; Swiss National Science Foundation; ETH Zurich; Max-Planck Society; ERC FX This work was supported, in whole or in part, by National Institutes of Health Director's Pioneer Award (Grant DP1 0D000839; to R. A. S.). This work was also supported by a Quan Fellowship (to R. M. W.), the Swiss National Science Foundation (to M. L. H.), ETH Zurich (to P. H. S.), the Max-Planck Society (to P. H. S.), and an ERC advanced grant (to P. H. S. and Harvard NeuroDiscovery Center). NR 56 TC 22 Z9 22 U1 1 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 6 PY 2013 VL 288 IS 36 BP 26275 EP 26288 DI 10.1074/jbc.M112.438937 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302RT UT WOS:000330623300057 PM 23867465 ER PT J AU Tanner, RM Calhoun, DA Bell, EK Bowling, CB Gutierrez, OM Irvin, MR Lackland, DT Oparil, S Warnock, D Muntner, P AF Tanner, Rikki M. Calhoun, David A. Bell, Emmy K. Bowling, C. Barrett Gutierrez, Orlando M. Irvin, Marguerite R. Lackland, Daniel T. Oparil, Suzanne Warnock, David Muntner, Paul TI Prevalence of Apparent Treatment-Resistant Hypertension among Individuals with CKD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; HIGH-BLOOD-PRESSURE; ENDOTHELIAL DYSFUNCTION; UNITED-STATES; RISK; MICROALBUMINURIA; ATHEROSCLEROSIS; SPIRONOLACTONE; PREVENTION; COMMITTEE AB Background and objectivesApparent treatment-resistant hypertension is defined as systolic/diastolic BP140/90 mmHg with concurrent use of three or more antihypertensive medication classes or use of four or more antihypertensive medication classes regardless of BP level.Design, setting, participants, & measurementsThe prevalence of apparent treatment-resistant hypertension among Reasons for Geographic and Racial Differences in Stroke study participants treated for hypertension (n=10,700) was determined by level of estimated GFR and albumin-to-creatinine ratio, and correlates of apparent treatment-resistant hypertension among those participants with CKD were evaluated. CKD was defined as an albumin-to-creatinine ratio30 mg/g or estimated GFR<60 ml/min per 1.73 m(2).ResultsThe prevalence of apparent treatment-resistant hypertension was 15.8%, 24.9%, and 33.4% for those participants with estimated GFR60, 45-59, and <45 ml/min per 1.73 m(2), respectively, and 12.1%, 20.8%, 27.7%, and 48.3% for albumin-to-creatinine ratio<10, 10-29, 30-299, and 300 mg/g, respectively. The multivariable-adjusted prevalence ratios (95% confidence intervals) for apparent treatment-resistant hypertension were 1.25 (1.11 to 1.41) and 1.20 (1.04 to 1.37) for estimated GFR levels of 45-59 and <45 ml/min per 1.73 m(2), respectively, versus 60 ml/min per 1.73 m(2) and 1.54 (1.39 to 1.71), 1.76 (1.57 to 1.97), and 2.44 (2.12 to 2.81) for albumin-to-creatinine ratio levels of 10-29, 30-299, and 300 mg/g, respectively, versus albumin-to-creatinine ratio<10 mg/g. After multivariable adjustment, men, black race, larger waist circumference, diabetes, history of myocardial infarction or stroke, statin use, and lower estimated GFR and higher albumin-to-creatinine ratio levels were associated with apparent treatment-resistant hypertension among individuals with CKD.ConclusionsThis study highlights the high prevalence of apparent treatment-resistant hypertension among individuals with CKD. C1 [Tanner, Rikki M.; Irvin, Marguerite R.; Muntner, Paul] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA. [Calhoun, David A.; Oparil, Suzanne] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Bell, Emmy K.; Gutierrez, Orlando M.; Warnock, David] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Bowling, C. Barrett] Univ Alabama Birmingham, Dept Med, Div Gerontol, Birmingham, AL 35294 USA. [Bowling, C. Barrett] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Lackland, Daniel T.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Muntner, P (reprint author), Univ Alabama Birmingham, Dept Epidemiol, 1665 Univ Blvd,Suite 230J, Birmingham, AL 35294 USA. EM pmuntner@uab.edu FU National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services [U01 NS041588]; Amgen Corporation FX This research project is supported by Cooperative Agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services. Additional funding was provided by an investigator-initiated grant-in-aid from Amgen Corporation. NR 26 TC 32 Z9 38 U1 0 U2 8 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP 6 PY 2013 VL 8 IS 9 BP 1583 EP 1590 DI 10.2215/CJN.00550113 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 235GR UT WOS:000325705500018 PM 23868902 ER PT J AU Weisbord, SD Gallagher, M Kaufman, J Cass, A Parikh, CR Chertow, GM Shunk, KA McCullough, PA Fine, MJ Mor, MK Lew, RA Huang, GD Conner, TA Brophy, MT Lee, J Soliva, S Palevsky, PM AF Weisbord, Steven D. Gallagher, Martin Kaufman, James Cass, Alan Parikh, Chirag R. Chertow, Glenn M. Shunk, Kendrick A. McCullough, Peter A. Fine, Michael J. Mor, Maria K. Lew, Robert A. Huang, Grant D. Conner, Todd A. Brophy, Mary T. Lee, Joanne Soliva, Susan Palevsky, Paul M. TI Prevention of Contrast-Induced AKI: A Review of Published Trials and the Design of the Prevention of Serious Adverse Events following Angiography (PRESERVE) Trial SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; RANDOMIZED CONTROLLED-TRIAL; PERCUTANEOUS CORONARY INTERVENTION; RADIOCONTRAST-INDUCED NEPHROPATHY; ELEVATION MYOCARDIAL-INFARCTION; INTRAVENOUS N-ACETYLCYSTEINE; ISOTONIC SODIUM-BICARBONATE; ASSOCIATION TASK-FORCE; RENAL-INSUFFICIENCY; PRIMARY ANGIOPLASTY AB Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial. C1 [Weisbord, Steven D.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. RP Weisbord, SD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Department of Veterans Affairs Cooperative Studies Program FX This work was supported by the Department of Veterans Affairs Cooperative Studies Program. NR 97 TC 35 Z9 35 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 SEP 6 PY 2013 VL 8 IS 9 BP 1618 EP 1631 DI 10.2215/CJN.11161012 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 235GR UT WOS:000325705500024 PM 23660180 ER PT J AU Best, LG Anderson, CM Saxena, R Almoguera, B Chandrupatla, H Martin, C Falcon, G Keplin, K Pearson, N Keating, BJ AF Best, Lyle G. Anderson, Cindy M. Saxena, Richa Almoguera, Berta Chandrupatla, Hareesh Martin, Candelaria Falcon, Gilbert Keplin, Kylie Pearson, Nichole Keating, Brendan J. TI IBC CARe Microarray Allelic Population Prevalences in an American Indian Population SO PLOS ONE LA English DT Article ID INTERNATIONAL HAPMAP PROJECT; LARGE GENE LISTS; GENOME; ASSOCIATION; VARIANTS AB Background: The prevalence of variant alleles among single nucleotide polymorphisms (SNPs) is not well known for many minority populations. These population allele frequencies (PAFs) are necessary to guide genetic epidemiology studies and to understand the population specific contribution of these variants to disease risk. Large differences in PAF among certain functional groups of genes could also indicate possible selection pressure or founder effects of interest. The 50K SNP, custom genotyping microarray (CARe) was developed, focusing on about 2,000 candidate genes and pathways with demonstrated pathophysiologic influence on cardiovascular disease (CVD). Methods: The CARe microarray was used to genotype 216 unaffected controls in a study of pre-eclampsia among a Northern Plains, American Indian tribe. The allelic prevalences of 34,240 SNPs suitable for analysis, were determined and compared with corresponding HapMap prevalences for the Caucasian population. Further analysis was conducted to compare the frequency of statistically different prevalences among functionally related SNPs, as determined by the DAVID Bioinformatics Resource. Results: Of the SNPs with PAFs in both datasets, 9.8%, 37.2% and 47.1% showed allele frequencies among the American Indian population greater than, less than and either greater or less than (respectively) the HapMap Caucasian population. The 2,547 genes were divided into 53 functional groups using the highest stringency criteria. While none of these groups reached the Bonferroni corrected p value of 0.00094, there were 7 of these 53 groups with significantly more or less differing PAFs, each with a probability of less than 0.05 and an overall probability of 0.0046. Conclusion: In comparison to the HapMap Caucasian population, there are substantial differences in the prevalence among an American Indian community of SNPs related to CVD. Certain functional groups of genes and related SNPs show possible evidence of selection pressure or founder effects. C1 [Best, Lyle G.; Martin, Candelaria; Falcon, Gilbert; Keplin, Kylie; Pearson, Nichole] Turtle Mt Community Coll, Dept Sci, Belcourt, ND USA. [Best, Lyle G.] Univ N Dakota, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. [Anderson, Cindy M.] Univ N Dakota, Coll Nursing, Grand Forks, ND 58201 USA. [Saxena, Richa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Almoguera, Berta; Chandrupatla, Hareesh; Keating, Brendan J.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. RP Best, LG (reprint author), Turtle Mt Community Coll, Dept Sci, Belcourt, ND USA. EM lbest@restel.com FU National Institute of General Medical Sciences of the National Institutes of Health [P20GM12345]; Department of Defense [W911NF-09-1-0016]; NIH NCRR [C06RR022088]; Robert Wood Johnson Foundation FX Research reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM12345, Grant Number W911NF-09-1-0016 from the Department of Defense, NIH NCRR (C06RR022088, Lindseth PI) and the Robert Wood Johnson Foundation, Nurse Faculty Scholar Award (Anderson). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 14 TC 0 Z9 0 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 6 PY 2013 VL 8 IS 9 AR e75080 DI 10.1371/journal.pone.0075080 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224BO UT WOS:000324856500104 PM 24040389 ER PT J AU Meeren, HKM de Gelder, B Ahlfors, SP Hamalainen, MS Hadjikhani, N AF Meeren, Hanneke K. M. de Gelder, Beatrice Ahlfors, Seppo P. Hamalainen, Matti S. Hadjikhani, Nouchine TI Different Cortical Dynamics in Face and Body Perception: An MEG study SO PLOS ONE LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN VISUAL-CORTEX; BRAIN-AREAS; FUSIFORM GYRUS; OCCIPITOTEMPORAL CORTEX; SOURCE LOCALIZATION; BODILY EXPRESSIONS; BIOLOGICAL MOTION AB Evidence from functional neuroimaging indicates that visual perception of human faces and bodies is carried out by distributed networks of face and body-sensitive areas in the occipito-temporal cortex. However, the dynamics of activity in these areas, needed to understand their respective functional roles, are still largely unknown. We monitored brain activity with millisecond time resolution by recording magnetoencephalographic (MEG) responses while participants viewed photographs of faces, bodies, and control stimuli. The cortical activity underlying the evoked responses was estimated with anatomically-constrained noise-normalised minimum-norm estimate and statistically analysed with spatiotemporal cluster analysis. Our findings point to distinct spatiotemporal organization of the neural systems for face and body perception. Face-selective cortical currents were found at early latencies (120-200 ms) in a widespread occipito-temporal network including the ventral temporal cortex (VTC). In contrast, early body-related responses were confined to the lateral occipito-temporal cortex (LOTC). These were followed by strong sustained body-selective responses in the orbitofrontal cortex from 200-700 ms, and in the lateral temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC region has a key role in the early processing of faces, but not of bodies. Instead, the LOTC, which includes the extra-striate body area (EBA), appears the dominant area for early body perception, whereas the VTC contributes to late and post-perceptual processing. C1 [Meeren, Hanneke K. M.; de Gelder, Beatrice] Tilburg Univ, NL-5000 LE Tilburg, Netherlands. [Ahlfors, Seppo P.; Hamalainen, Matti S.; Hadjikhani, Nouchine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP de Gelder, B (reprint author), Tilburg Univ, NL-5000 LE Tilburg, Netherlands. EM b.degelder@uvt.nl RI Hadjikhani, Nouchine/C-2018-2008; Hamalainen, Matti/C-8507-2013; Ahlfors, Seppo/P-3644-2016 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU National Institute of Health (NIH) [RO1NS44824, 5R01EB009048, 5R01NS037462, R01NS57500]; Netherlands Organization for Scientific Research (NWO) [R 95-403, 451-05-014]; MIND institute; Center for Functional Neuroimaging Technologies (NIH) [P41 RR14075]; Swiss National Foundation [PPOOP3_130191]; Human Frontier Science Program [RGP0054/2004-C]; EU [FDP6-NEST-043403]; TANGO (FP7 FET-Open) FX This work was supported by the National Institute of Health (NIH) (grant number RO1NS44824 to NH) and the Netherlands Organization for Scientific Research (NWO grants number R 95-403 and number 451-05-014 to HKMM). MSH, SPA and BdG were supported by the MIND institute, MSH by the Center for Functional Neuroimaging Technologies (NIH grant number P41 RR14075) as well as NIH grants 5R01EB009048 and 5R01NS037462, SPA by NIH grant R01NS57500 and NH by the Swiss National Foundation (PPOOP3_130191). Partial support was also provided by the Human Frontier Science Program (grant number RGP0054/2004-C) and the EU project grants COBOL (FDP6-NEST-043403) and TANGO (FP7 FET-Open) to BdG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 90 TC 15 Z9 16 U1 1 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 6 PY 2013 VL 8 IS 9 AR e71408 DI 10.1371/journal.pone.0071408 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224BO UT WOS:000324856500005 PM 24039712 ER PT J AU Million, M Zhao, JF Luckey, A Czimmer, J Maynard, GD Kehne, J Hoffman, DC Tache, Y AF Million, Mulugeta Zhao, Jing-Fang Luckey, Andrew Czimmer, Jozsef Maynard, George D. Kehne, John Hoffman, Diane C. Tache, Yvette TI The Newly Developed CRF1-Receptor Antagonists, NGD 98-2 and NGD 9002, Suppress Acute Stress-Induced Stimulation of Colonic Motor Function and Visceral Hypersensitivity in Rats SO PLOS ONE LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; CRF1 RECEPTOR ANTAGONIST; FACTOR SIGNALING PATHWAYS; FACTOR TYPE-1 RECEPTOR; COLORECTAL DISTENSION; NONPEPTIDE ANTAGONIST; RECTAL DISTENSION; MAJOR DEPRESSION; PAIN AB Corticotropin releasing factor receptor 1 (CRF1) is the key receptor that mediates stress-related body responses. However to date there are no CRF1 antagonists that have shown clinical efficacy in stress-related diseases. We investigated the inhibitory effects of a new generation, topology 2 selective CRF1 antagonists, NGD 98-2 and NGD 9002 on exogenous and endogenous CRF-induced stimulation of colonic function and visceral hypersensitivity to colorectal distension (CRD) in conscious rats. CRF1 antagonists or vehicle were administered orogastrically (og) or subcutaneously (sc) before either intracerebroventricular (icv) or intraperitoneal (ip) injection of CRF (10 mu g/kg), exposure to water avoidance stress (WAS, 60 min) or repeated CRD (60 mmHg twice, 10 min on/off at a 30 min interval). Fecal pellet output (FPO), diarrhea and visceromotor responses were monitored. In vehicle (og)-pretreated rats, icv CRF stimulated FPO and induced diarrhea in >50% of rats. NGD 98-2 or NGD 9002 (3, 10 and 30 mg/kg, og) reduced the CRF-induced FPO response with an inhibitory IC50 of 15.7 and 4.3 mg/kg respectively. At the highest dose, og NGD 98-2 or NGD 9002 blocked icv CRF-induced FPO by 67-87% and decreased WAS-induced-FPO by 23-53%. When administered sc, NGD 98-2 or NGD 9002 (30 mg/kg) inhibited icv and ip CRF-induced-FPO. The antagonists also prevented the development of nociceptive hyper-responsivity to repeated CRD. These data demonstrate that topology 2 CRF1 antagonists, NGD 98-2 and NGD 9002, administered orally, prevented icv CRF-induced colonic secretomotor stimulation, reduced acute WAS-induced defecation and blocked the induction of visceral sensitization to repeated CRD. C1 [Million, Mulugeta; Zhao, Jing-Fang; Luckey, Andrew; Czimmer, Jozsef; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. [Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Oppenheimer Family Ctr Neurobiol Stress, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. [Million, Mulugeta; Zhao, Jing-Fang; Luckey, Andrew; Czimmer, Jozsef; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Maynard, George D.; Kehne, John; Hoffman, Diane C.] Neurogen Corp, Branford, CT USA. RP Million, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. EM millionmulugeta@mednet.ucla.edu FU Neurogen-Aventis CRF Collaboration, Branford, Connecticut, USA; Veterans Administration Research Career Scientist Award; NIH [RO1 DK-078676, R01 DK-57238, P50 DK-64539, DK-41301] FX This work was supported by an investigator initiated fund from the Neurogen-Aventis CRF Collaboration, Branford, Connecticut, USA (YT, MM); The Veterans Administration Research Career Scientist Award (YT), Center Grant NIH DK-41301 (Animal Model Core, YT, MM); RO1 DK-078676 (MM); R01 DK-57238 (YT) and P50 DK-64539 (YT, MM). The funders had no decision role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 10 Z9 10 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 6 PY 2013 VL 8 IS 9 AR e73749 DI 10.1371/journal.pone.0073749 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224BO UT WOS:000324856500059 PM 24040053 ER PT J AU Wesemann, DR Portuguese, AJ Meyers, RM Gallagher, MP Cluff-Jones, K Magee, JM Panchakshari, RA Rodig, SJ Kepler, TB Alt, FW AF Wesemann, Duane R. Portuguese, Andrew J. Meyers, Robin M. Gallagher, Michael P. Cluff-Jones, Kendra Magee, Jennifer M. Panchakshari, Rohit A. Rodig, Scott J. Kepler, Thomas B. Alt, Frederick W. TI Microbial colonization influences early B-lineage development in the gut lamina propria SO NATURE LA English DT Article ID ANTIBODY REPERTOIRE DEVELOPMENT; CELL DEVELOPMENT; RAG EXPRESSION; RECOMBINATION; IMMUNIZATION; TOLERANCE; GENES; MOUSE; FETAL; MICE AB The RAG1/RAG2 endonuclease (RAG) initiates the V(D)J recombination reaction that assembles immunoglobulin heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires(1). IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH mu and IgL (Ig kappa or Ig lambda) chains generates IgM, which is expressed on immature B cells as the B-cell antigen-binding receptor (BCR). Rag expression can continue in immature B cells(2), allowing continued Ig kappa V(D)J recombination that replaces the initial V kappa J kappa exon with one that generates a new specificity(3-5). This 'receptor editing' process, which can also lead to Ig lambda V(D)J recombination and expression(3,6,7), provides a mechanism whereby antigen encounter at the Rag-expressing immature B-cell stage helps shape pre-immune BCR repertoires. As the major site of postnatal B-cell development, the bone marrow is the principal location of primary immunoglobulin repertoire diversification in mice. Here we report that early B-cell development also occurs within the mouse intestinal lamina propria (LP), where the associated V(D)J recombination/receptor editing processes modulate primary LP immunoglobulin repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B-lineage cells that harbour intermediates indicative of ongoing V(D)J recombination and which contain cells with pro-B, pre-B and editing phenotypes. Consistent with LP-specific receptor editing, Rag-expressing LP B-lineage cells have similar V-H repertoires, but significantly different V kappa repertoires, compared to those of Rag2-expressing bone marrow counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of Ig lambda-expressing versus Ig kappa-expressing B cells specifically in the LP. We conclude that B-cell development occurs in the intestinal mucosa, where it is regulated by extracellular signals from commensal microbes that influence gut immunoglobulin repertoires. C1 [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Wesemann, Duane R.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kepler, Thomas B.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02215 USA. RP Alt, FW (reprint author), Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. EM dwesemann@research.bwh.harvard.edu; alt@enders.tch.harvard.edu FU National Institutes of Health [AI020047, AI89972, HHSN272201000053C]; Lymphoma and Leukemia SCOR [7009-12]; American Academy of Allergy Asthma and Immunology; CSL-Behring; Career Award for Medical Scientists from the Burroughs Wellcome Fund FX This work was supported by National Institutes of Health grants AI020047 (to F. W. A.) and AI89972 (to D. R. W.), Lymphoma and Leukemia SCOR 7009-12 (to F. W. A.), and National Institutes of Health research contract HHSN272201000053C (to T. B. K.). D. R. W. was also supported by an award from the American Academy of Allergy Asthma and Immunology and CSL-Behring and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. F. W. A. is an Investigator of the Howard Hughes Medical Institute. NR 30 TC 58 Z9 63 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD SEP 5 PY 2013 VL 501 IS 7465 DI 10.1038/nature12496 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL8YC UT WOS:000339424700001 PM 23965619 ER PT J AU Byakika-Tusiime, J Polley, EC Oyugi, JH Bangsberg, DR AF Byakika-Tusiime, Jayne Polley, Eric C. Oyugi, Jessica H. Bangsberg, David R. TI Free HIV Antiretroviral Therapy Enhances Adherence among Individuals on Stable Treatment: Implications for Potential Shortfalls in Free Antiretroviral Therapy SO PLOS ONE LA English DT Article ID MARGINAL STRUCTURAL MODELS; BARRIERS; EPIDEMIOLOGY; KAMPALA; UGANDA; ADULTS; HAART; TIME AB Objective: To estimate the population-level causal effect of source of payment for HIV medication on treatment adherence using Marginal Structural Models. Methods: Data were obtained from an observational cohort of 76 HIV-infected individuals with at least 24 weeks of antiretroviral therapy treatment from 2002 to 2007 in Kampala, Uganda. Adherence was the primary outcome and it was measured using the 30-day visual analogue scale. Marginal structural models (MSM) were used to estimate the effect of source of payment for HIV medication on adherence, adjusting for confounding by income, duration on antiretroviral therapy (ART), timing of visit, prior adherence, prior CD4(+) T cell count and prior plasma HIV RNA. Traditional association models were also examined and the results compared. Results: Free HIV treatment was associated with a 3.8% improvement in adherence in the marginal structural model, while the traditional statistical models showed a 3.1-3.3% improvement in adherence associated with free HIV treatment. Conclusion: Removing a financial barrier to treatment with ART by providing free HIV treatment appears to significantly improve adherence to antiretroviral therapy. With sufficient information on confounders, MSMs can be used to make robust inferences about causal effects in epidemiologic research. C1 [Byakika-Tusiime, Jayne] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Kampala, Uganda. [Polley, Eric C.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Oyugi, Jessica H.] Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp Global Hlth, Dept Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. RP Byakika-Tusiime, J (reprint author), Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Kampala, Uganda. EM tusjayne@hotmail.com FU National Institutes of Health [NIMH RO-154907, NIMH RO-3 66654, NIAAA R-21 014784, NIMH K-24 87227]; Fogarty AIDS International Training and Research Program/University of California, Berkeley [1D43 TW00003] FX This work was supported partly by the National Institutes of Health (NIMH RO-154907, NIMH RO-3 66654, NIAAA R-21 014784, NIMH K-24 87227) and the Fogarty AIDS International Training and Research Program/University of California, Berkeley (1D43 TW00003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 1 Z9 1 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 5 PY 2013 VL 8 IS 9 AR e70375 DI 10.1371/journal.pone.0070375 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219CG UT WOS:000324481600005 PM 24039704 ER PT J AU Cron, KR Zhu, KY Kushwaha, DS Hsieh, G Merzon, D Rameseder, J Chen, CC D'Andrea, AD Kozono, D AF Cron, Kyle R. Zhu, Kaya Kushwaha, Deepa S. Hsieh, Grace Merzon, Dmitry Rameseder, Jonathan Chen, Clark C. D'Andrea, Alan D. Kozono, David TI Proteasome Inhibitors Block DNA Repair and Radiosensitize Non-Small Cell Lung Cancer SO PLOS ONE LA English DT Article ID NF-KAPPA-B; DOUBLE-STRAND BREAKS; MULTIPLE-MYELOMA; MAMMALIAN-CELLS; GENE-EXPRESSION; SOLID TUMORS; BORTEZOMIB; ADENOCARCINOMA; RECOMBINATION; CHEMOTHERAPY AB Despite optimal radiation therapy (RT), chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC) fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and proteasome inhibition showed synergistic effects. Proteasome inhibition resulted in an 80-90% decrease in homologous recombination (HR), a 50% decrease in expression of NF-kappa B-inducible HR genes BRCA1 and FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced foci. I kappa B alpha RNAi knockdown rescued NSCLC radioresistance. Irradiation of mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly increased murine survival compared to either treatment alone. Proteasome inhibition is a promising strategy for NSCLC radiosensitization via inhibition of NF-kappa B-mediated expression of Fanconi Anemia/HR DNA repair genes. C1 [Cron, Kyle R.; Zhu, Kaya; Kushwaha, Deepa S.; Hsieh, Grace; Merzon, Dmitry; D'Andrea, Alan D.; Kozono, David] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Rameseder, Jonathan] MIT, Cambridge, MA 02139 USA. [Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, San Diego, CA 92103 USA. [D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kozono, D (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM dkozono@lroc.harvard.edu FU American Society for Radiation Oncology (ASTRO) Junior Faculty Career Research Training Award; Joint Center for Radiation Therapy Foundation Grant; Dana-Farber/Harvard Cancer Center SPORE Developmental Research Project Award in Lung Cancer Research; National Cancer Institute of the National Institutes of Health [K08CA172354] FX This research was supported by an American Society for Radiation Oncology (ASTRO) Junior Faculty Career Research Training Award, a Joint Center for Radiation Therapy Foundation Grant, a Dana-Farber/Harvard Cancer Center SPORE Developmental Research Project Award in Lung Cancer Research, and the National Cancer Institute of the National Institutes of Health under Award Number K08CA172354. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 17 Z9 17 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 5 PY 2013 VL 8 IS 9 AR e73710 DI 10.1371/journal.pone.0073710 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219CG UT WOS:000324481600093 PM 24040035 ER PT J AU Scott, JC Klein, BA Duran-Pinedo, A Hu, LD Duncan, MJ AF Scott, Jodie C. Klein, Brian A. Duran-Pinedo, Ana Hu, Linden Duncan, Margaret J. TI A Two-Component System Regulates Hemin Acquisition in Porphyromonas gingivalis SO PLOS ONE LA English DT Article ID CYSTEINE PROTEINASE; RESPONSE REGULATOR; EPITHELIAL-CELLS; GENOME SEQUENCE; OUTER-MEMBRANE; STRAIN W83; GENES; IDENTIFICATION; HEMOGLOBIN; TRANSPORTERS AB Porphyromonas gingivalis is a Gram-negative oral anaerobe associated with infection of the periodontia. The organism has a small number of two-component signal transduction systems, and after comparing genome sequences of strains W83 and ATCC 33277 we discovered that the latter was mutant in histidine kinase (PGN_0752), while the cognate response regulator (PGN_0753) remained intact. Microarray-based transcriptional profiling and ChIP-seq assays were carried out with an ATCC 33277 transconjugant containing the functional histidine kinase from strain W83 (PG0719). The data showed that the regulon of this signal transduction system contained genes that were involved in hemin acquisition, including gingipains, at least three transport systems, as well as being self-regulated. Direct regulation by the response regulator was confirmed by electrophoretic mobility shift assays. In addition, the system appears to be activated by hemin and the regulator acts as both an activator and repressor. C1 [Scott, Jodie C.; Duran-Pinedo, Ana; Duncan, Margaret J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Klein, Brian A.] Tufts Univ, Sackler Sch Biomed Sci, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Hu, Linden] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Microbiol, Cambridge, MA USA. EM mduncan@forsyth.org RI Hu, Linden/L-6314-2016; OI Hu, Linden/0000-0003-1659-5558; Klein, Brian/0000-0002-7233-2114 FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01 DE015931, F31 DE02249, R21 DE016859] FX Research reported in this publication was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award numbers R01 DE015931 (MD), F31 DE02249 (BK), and R21 DE016859 (LTH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 8 Z9 8 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 5 PY 2013 VL 8 IS 9 AR e73351 DI 10.1371/journal.pone.0073351 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219CG UT WOS:000324481600066 PM 24039921 ER PT J AU Sudore, RL Stewart, AL Knight, SJ McMahan, RD Feuz, M Miao, YH Barnes, DE AF Sudore, Rebecca L. Stewart, Anita L. Knight, Sara J. McMahan, Ryan D. Feuz, Mariko Miao, Yinghui Barnes, Deborah E. TI Development and Validation of a Questionnaire to Detect Behavior Change in Multiple Advance Care Planning Behaviors SO PLOS ONE LA English DT Article ID DIVERSE OLDER-ADULTS AB Introduction: Advance directives have traditionally been considered the gold standard for advance care planning. However, recent evidence suggests that advance care planning involves a series of multiple discrete behaviors for which people are in varying stages of behavior change. The goal of our study was to develop and validate a survey to measure the full advance care planning process. Methods: The Advance Care Planning Engagement Survey assesses "Process Measures'' of factors known from Behavior Change Theory to affect behavior (knowledge, contemplation, self-efficacy, and readiness, using 5-point Likert scales) and "Action Measures'' (yes/no) of multiple behaviors related to surrogate decision makers, values and quality of life, flexibility for surrogate decision making, and informed decision making. We administered surveys at baseline and 1 week later to 50 diverse, older adults from San Francisco hospitals. Internal consistency reliability of Process Measures was assessed using Cronbach's alpha (only continuous variables) and test-retest reliability of Process and Action Measures was examined using intraclass correlations. For discriminant validity, we compared Process and Action Measure scores between this cohort and 20 healthy college students (mean age 23.2 years, SD 2.7). Results: Mean age was 69.3 (SD 10.5) and 42% were non-White. The survey took a mean of 21.4 minutes (+/- 6.2) to administer. The survey had good internal consistency (Process Measures Cronbach's alpha, 0.94) and test-retest reliability (Process Measures intraclass correlation, 0.70; Action Measures, 0.87). Both Process and Action Measure scores were higher in the older than younger group, p<.001. Conclusion: A new Advance Care Planning Engagement Survey that measures behavior change (knowledge, contemplation, self-efficacy, and readiness) and multiple advance care planning actions demonstrates good reliability and validity. Further research is needed to assess whether survey scores improve in response to advance care planning interventions and whether scores are associated with receipt of care consistent with one's wishes. C1 [Sudore, Rebecca L.; McMahan, Ryan D.; Feuz, Mariko; Miao, Yinghui; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Sudore, Rebecca L.; Feuz, Mariko; Miao, Yinghui] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Stewart, Anita L.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA USA. [Knight, Sara J.] Vet Adm, Hlth Serv Res & Dev Serv, Washington, DC USA. [Knight, Sara J.; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Sudore, RL (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM rebecca.sudore@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSRD; National Palliative Care Research Center; National Institute on Aging, National Institutes of Health [P30-AG15272] FX This study was funded in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, HSR&D, the National Palliative Care Research Center, and by Grant P30-AG15272 under the Resource Centers for Minority Aging Research program by the National Institute on Aging, National Institutes of Health. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. NR 20 TC 12 Z9 12 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 5 PY 2013 VL 8 IS 9 AR e72465 DI 10.1371/journal.pone.0072465 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219CG UT WOS:000324481600032 PM 24039772 ER PT J AU Huang, E Ngo, M Yee, S Held, L Norman, K Scremin, AME Scremin, O AF Huang, Emerald Ngo, Mai Yee, Stuart Held, Laura Norman, Keith Scremin, A. M. Erika Scremin, Oscar TI Repeated blast exposure alters open field behavior recorded under low illumination SO BRAIN RESEARCH LA English DT Article DE Brain injury; Blast injury; Rat ID TRAUMATIC BRAIN-INJURY; RAT; CONCUSSION; HEADACHE; MODEL; MICE; AGE AB Blast-induced traumatic brain injury (bTBI) can have devastating behavioral consequences. This study was designed to evaluate the behavioral consequences of single or repeated bTBI, as evaluated by an open field (OF) test conducted in near-darkness to avoid confounding effects of illumination and photophobia. Sprague-Dawley rats under isoflurane anesthesia were exposed to a series of 3 sub-lethal blasts into a compressed air-driven blast chamber separated by 2 week intervals (n=11). Sham controls received anesthesia but without blast exposure (n=11). OF tests were performed 1 or 7 days after each blast using a computerized video tracking system in near-darkness to monitor spontaneous activity. Spatial and temporal variables calculated for both blast and sham groups were: Distance moved (cm) and time (s) spent in the center or periphery zones of the field, total distance traveled, speed in center and periphery zones, rearing events and non-linear regressions of distance moved and rearing events on time. Results showed that the sham group expressed the expected decrease (habituation) in total distance walked, and distance walked as well as speed in center and periphery in successive exposures to the OF while the blast group did not, a sign of impaired learning. The blast group also walked more and faster and demonstrated more rearing behavior, both considered OF signs of anxiety. These results indicate that OF outcomes of bTBI in animals have resemblance to alterations observed in human subjects with this condition and might be useful in evaluating the response of behavioral outcomes of bTBI to experimental treatments. Published by Elsevier B.V. C1 [Huang, Emerald; Ngo, Mai; Yee, Stuart] Univ Calif Los Angeles, VA Multicampus Residency Program, Los Angeles, CA USA. [Held, Laura; Scremin, A. M. Erika] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Norman, Keith; Scremin, Oscar] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Scremin, A. M. Erika] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Scremin, Oscar] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Scremin, O (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Res, 11301 Wilshire Blvd,Bldg 115,Room 319, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu FU Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VARRD) [B5089R]; VA RR&D Research Career Scientist award FX This work was supported by Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VARR&D) #B5089R, and a VA RR&D Research Career Scientist award (to O.U.S.). NR 29 TC 3 Z9 3 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 5 PY 2013 VL 1529 BP 125 EP 133 DI 10.1016/j.brainres.2013.06.042 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 221KQ UT WOS:000324658200013 PM 23850767 ER PT J AU Koreth, J Ritz, J AF Koreth, John Ritz, Jerome TI Tregs, HSCT, and acute GVHD: up close and personal SO BLOOD LA English DT Editorial Material ID REGULATORY T-CELLS; VERSUS-HOST-DISEASE C1 [Koreth, John; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA183559, R01 CA183560] NR 10 TC 3 Z9 3 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 5 PY 2013 VL 122 IS 10 BP 1690 EP 1691 DI 10.1182/blood-2013-07-514125 PG 4 WC Hematology SC Hematology GA 213KX UT WOS:000324057100003 PM 24009174 ER PT J AU Proctor, EK Landsverk, J Baumann, AA Mittman, BS Aarons, GA Brownson, RC Glisson, C Chambers, D AF Proctor, Enola K. Landsverk, John Baumann, Ana A. Mittman, Brian S. Aarons, Gregory A. Brownson, Ross C. Glisson, Charles Chambers, David TI The implementation research institute: training mental health implementation researchers in the United States SO IMPLEMENTATION SCIENCE LA English DT Article DE Dissemination research; Implementation research; Training; Translational research ID COMORBIDITY SURVEY REPLICATION; KNOWLEDGE TRANSLATION; DISSEMINATION; SCIENCE; STRATEGIES; DISORDERS; FRAMEWORK; TRAINEES; SERVICES; QUALITY AB Background: The Implementation Research Institute (IRI) provides two years of training in mental health implementation science for 10 new fellows each year. The IRI is supported by a National Institute of Mental Health (NIMH) R25 grant and the Department of Veterans Affairs (VA). Fellows attend two annual week-long trainings at Washington University in St. Louis. Training is provided through a rigorous curriculum, local and national mentoring, a 'learning site visit' to a federally funded implementation research project, pilot research, and grant writing. Methods: This paper describes the rationale, components, outcomes to date, and participant experiences with IRI. Results: IRI outcomes include 31 newly trained implementation researchers, their new grant proposals, contributions to other national dissemination and implementation research training, and publications in implementation science authored by the Core Faculty and fellows. Former fellows have obtained independent research funding in implementation science and are beginning to serve as mentors for more junior investigators. Conclusions: Based on the number of implementation research grant proposals and papers produced by fellows to date, the IRI is proving successful in preparing new researchers who can inform the process of making evidence-based mental healthcare more available through real-world settings of care and who are advancing the field of implementation science. C1 [Proctor, Enola K.; Baumann, Ana A.] Washington Univ, George Warren Brown Sch Social Work, Ctr Mental Hlth Serv Res, St Louis, MO 63130 USA. [Landsverk, John] San Diego Childrens Hosp, Child & Adolescent Serv Res Ctr, San Diego, CA USA. [Mittman, Brian S.] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. [Aarons, Gregory A.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Brownson, Ross C.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Glisson, Charles] Univ Tennessee, Childrens Mental Hlth Serv Res Ctr, Knoxville, TN USA. [Chambers, David] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Proctor, EK (reprint author), Washington Univ, George Warren Brown Sch Social Work, Ctr Mental Hlth Serv Res, 1 Brookings Dr Campus,Box 1196, St Louis, MO 63130 USA. EM ekp@wustl.edu OI Baumann, Ana/0000-0002-4523-0147; Mittman, Brian/0000-0003-3589-9178 FU National Institute of Mental Health through the Center for Mental Health Services Research [NIMH P30 MH068579]; National Institute of Mental Health through the Implementation Research Institute [NIMH R25 MH080916]; US Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI) FX Preparation of this paper was supported by the National Institute of Mental Health through the Center for Mental Health Services Research (NIMH P30 MH068579) and the Implementation Research Institute (NIMH R25 MH080916) and the US Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI). We gratefully acknowledge learning site hosts who make invaluable contribution to IRI training; administrative support from the Brown School, Washington University in St. Louis; and the volunteer research assistants who contribute to the Institute's success. NR 30 TC 11 Z9 11 U1 4 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD SEP 5 PY 2013 VL 8 AR 105 DI 10.1186/1748-5908-8-105 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 214JQ UT WOS:000324129400001 PM 24007290 ER PT J AU Menees, DS Peterson, ED Wang, Y Curtis, JP Messenger, JC Rumsfeld, JS Gurm, HS AF Menees, Daniel S. Peterson, Eric D. Wang, Yongfei Curtis, Jeptha P. Messenger, John C. Rumsfeld, John S. Gurm, Hitinder S. TI Door-to-Balloon Time and Mortality among Patients Undergoing Primary PCI SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE-MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; CARDIOVASCULAR DATA REGISTRY; PRIMARY ANGIOPLASTY; REPERFUSION; STRATEGIES; OUTCOMES; QUALITY; TRENDS; ASSOCIATION AB BACKGROUND Current guidelines for the treatment of ST-segment elevation myocardial infarction recommend a door-to-balloon time of 90 minutes or less for patients undergoing primary percutaneous coronary intervention (PCI). Door-to-balloon time has become a performance measure and is the focus of regional and national quality-improvement initiatives. However, it is not known whether national improvements in door-to-balloon times have been accompanied by a decline in mortality. METHODS We analyzed annual trends in door-to-balloon times and in-hospital mortality using data from 96,738 admissions for patients undergoing primary PCI for ST-segment elevation myocardial infarction from July 2005 through June 2009 at 515 hospitals participating in the CathPCI Registry. In a subgroup analysis using a linked Medicare data set, we assessed 30-day mortality. RESULTS Median door-to-balloon times declined significantly, from 83 minutes in the 12 months from July 2005 through June 2006 to 67 minutes in the 12 months from July 2008 through June 2009 (P<0.001). Similarly, the percentage of patients for whom the door-to-balloon time was 90 minutes or less increased from 59.7% in the first year to 83.1% in the last year (P<0.001). Despite improvements in door-to-balloon times, there was no significant overall change in unadjusted in-hospital mortality (4.8% in 2005-2006 and 4.7% in 2008-2009, P=0.43 for trend) or in risk-adjusted in-hospital mortality (5.0% in 2005-2006 and 4.7% in 2008-2009, P=0.34), nor was a significant difference observed in unadjusted 30-day mortality (P=0.64). CONCLUSIONS Although national door-to-balloon times have improved significantly for patients undergoing primary PCI for ST-segment elevation myocardial infarction, in-hospital mortality has remained virtually unchanged. These data suggest that additional strategies are needed to reduce in-hospital mortality in this population. C1 [Menees, Daniel S.; Gurm, Hitinder S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Menees, Daniel S.; Gurm, Hitinder S.] Vet Affairs VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Peterson, Eric D.] Duke Univ, Durham, NC USA. [Wang, Yongfei; Curtis, Jeptha P.] Yale Univ, New Haven, CT USA. [Messenger, John C.; Rumsfeld, John S.] Univ Colorado, Sch Med, Aurora, CO USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. RP Menees, DS (reprint author), Univ Michigan, Dept Internal Med, Div Cardiovasc Med, 1500 East Med Ctr Dr,2A396, Ann Arbor, MI 48109 USA. EM dmenees@umich.edu OI Gurm, Hitinder/0000-0002-1646-0218 FU National Cardiovascular Data Registry of the American College of Cardiology Foundation FX Funded by the National Cardiovascular Data Registry of the American College of Cardiology Foundation. NR 23 TC 181 Z9 187 U1 0 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 5 PY 2013 VL 369 IS 10 BP 901 EP 909 DI 10.1056/NEJMoa1208200 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 211KV UT WOS:000323906900007 PM 24004117 ER PT J AU Shlipak, MG Matsushita, K Arnlov, J Inker, LA Katz, R Polkinghorne, KR Rothenbacher, D Sarnak, MJ Astor, BC Coresh, J Levey, AS Gansevoort, RT AF Shlipak, Michael G. Matsushita, Kunihiro Arnlov, Johan Inker, Lesley A. Katz, Ronit Polkinghorne, Kevan R. Rothenbacher, Dietrich Sarnak, Mark J. Astor, Brad C. Coresh, Josef Levey, Andrew S. Gansevoort, Ron T. CA CKD Prognosis Consortium TI Cystatin C versus Creatinine in Determining Risk Based on Kidney Function SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; COLLABORATIVE METAANALYSIS; POPULATION COHORTS; HIGHER ALBUMINURIA; ESTIMATED GFR; ALL-CAUSE; GENERAL-POPULATION; HEART-FAILURE; CKD-EPI AB BACKGROUND Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined. METHODS We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C. RESULTS In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR. CONCLUSIONS The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. C1 [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med Epidemiol & Biostat, San Francisco, CA 94143 USA. [Matsushita, Kunihiro; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Arnlov, Johan] Geriatr Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Arnlov, Johan] Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden. [Inker, Lesley A.; Sarnak, Mark J.; Levey, Andrew S.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Katz, Ronit] Univ Washington, Seattle, WA 98195 USA. [Polkinghorne, Kevan R.] Monash Univ, Dept Nephrol, Monash Med Ctr, Melbourne, Vic 3004, Australia. [Polkinghorne, Kevan R.] Monash Univ, Dept Med, Melbourne, Vic, Australia. [Rothenbacher, Dietrich] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Rothenbacher, Dietrich] Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany. [Astor, Brad C.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. RP Coresh, J (reprint author), Chron Kidney Dis Prognosis Consortium Data Coordi, 615 Wolfe St, Baltimore, MD 21205 USA. RI Arnlov, Johan/N-9886-2013; Schottker, Ben/F-8183-2014; Wetzels, Jack/A-1720-2014; Kronenberg, Florian/B-1736-2008; Brenner, Hermann/B-4627-2017; OI Schottker, Ben/0000-0002-1217-4521; Kronenberg, Florian/0000-0003-2229-1120; Brenner, Hermann/0000-0002-6129-1572; Klein, Ronald/0000-0002-4428-6237; Townend, Jonathan/0000-0002-5881-5806 FU National Kidney Foundation FX Funded by the National Kidney Foundation and others. NR 52 TC 220 Z9 235 U1 2 U2 28 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 5 PY 2013 VL 369 IS 10 BP 932 EP 943 DI 10.1056/NEJMoa1214234 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 211KV UT WOS:000323906900010 PM 24004120 ER PT J AU Prabhakar, AM Harvey, HB Oklu, R AF Prabhakar, Anand M. Harvey, H. Benjamin Oklu, Rahmi TI The Medical Device Excise Tax - Over before It Begins? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Prabhakar, Anand M.; Harvey, H. Benjamin; Oklu, Rahmi] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rahmioklu@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 5 PY 2013 VL 369 IS 10 BP 983 EP 984 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 211KV UT WOS:000323906900027 PM 24004139 ER PT J AU Peyre, M Stemmer-Rachamimov, A Clermont-Taranchon, E Quentin, S El-Taraya, N Walczak, C Volk, A Niwa-Kawakita, M Karboul, N Giovannini, M Kalamarides, M AF Peyre, M. Stemmer-Rachamimov, A. Clermont-Taranchon, E. Quentin, S. El-Taraya, N. Walczak, C. Volk, A. Niwa-Kawakita, M. Karboul, N. Giovannini, M. Kalamarides, M. TI Meningioma progression in mice triggered by Nf2 and Cdkn2ab inactivation SO ONCOGENE LA English DT Article DE meningioma; adenovirus; NF2; CDKN2AB; mouse model ID ANAPLASTIC MENINGIOMAS; TUMOR-SUPPRESSOR; MALIGNANT PROGRESSION; SPORADIC MENINGIOMAS; DCE-MRI; P16(INK4A); GENE; BEVACIZUMAB; SENESCENCE; BENIGN AB Aggressive variants of meningiomas (WHO grade II and III) represent up to 30% of those tumors that are among the most common primary central nervous system tumors in adults. Currently, there is no effective treatment for grade-II and -III meningiomas, the main treatment remaining surgical excision. Genetic studies have highlighted two main events associated with meningioma progression: an increase of chromosomal instability in tumors with NF2 inactivation and homozygous deletions or point mutations of the CDKN2AB locus. In this study we demonstrated that in mice, in addition to bi-allelic Nf2 inactivation, homozygous and heterozygous Adenovirus Cre-mediated Cdkn2ab deletions lead to increased meningioma frequency (72% and 50%, respectively) with a shorter latency (3.5 and 7.8 months, respectively) compared with control cohorts and induce grade II/III meningioma progression with an incidence of 34% and 28%, respectively. Moreover, Cdkn2ab inactivation in arachnoidal cells was associated with decreased senescence compared with Nf2(-/-) and wild-type arachnoidal cells in vitro. We have established three mouse meningioma cell lines and generated a syngenic orthotopic meningioma mouse model with 50-100% grade-II/III meningiomas after reimplantation. Comparative genomic hybridization of four meningiomas from Cdkn2ab homozygous mice and three cell cultures revealed the absence of unbalanced chromosomal segments in tumors and several chromosome imbalances in cell cultures. In addition, we were able to detect meningiomas by using bioluminescence and to evaluate tumor vascular permeability by dynamic magnetic resonance imaging. These results show that Nf2 and Cdkn2ab cooperate to promote meningioma progression in mice. The short latency of tumor development and the ability to derive grade II/III meningioma cell cultures are key aspects of this model to promote its use in pre-clinical drug testing. C1 [Peyre, M.; Kalamarides, M.] Hop Beaujon, AP HP, Dept Neurosurg, F-92110 Clichy, France. [Peyre, M.; Clermont-Taranchon, E.; Niwa-Kawakita, M.; Karboul, N.; Kalamarides, M.] Univ Paris 07, Paris, France. [Peyre, M.; Clermont-Taranchon, E.; Niwa-Kawakita, M.; Karboul, N.; Kalamarides, M.] Fdn Jean Dausset, Unite Inserm U674, Paris, France. [Stemmer-Rachamimov, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathol, Boston, MA USA. [Quentin, S.] Inst Univ Hematol, INSERM, U944, Paris, France. [El-Taraya, N.; Walczak, C.; Volk, A.] Univ Paris 11, INSERM, U759, F-91405 Orsay, France. [El-Taraya, N.; Walczak, C.; Volk, A.] Inst Curie, Ctr Rech, F-91405 Orsay, France. [Giovannini, M.] House Res Inst, Los Angeles, CA USA. RP Kalamarides, M (reprint author), Hop Beaujon, AP HP, Dept Neurosurg, 100 Blvd Gen Leclerc, F-92110 Clichy, France. EM michel.kalamarides@bjn.aphp.fr FU Association pour la Recherche sur le Cancer; Ligue Nationale contre le Cancer-comite Paris; Fondation Anber; Association Neurofibromatoses et Recklinghausen; Inserm FX We thank A Berns for Ink4ab-/+ mutant mice, M Pla and staff of the Institut Universitaire d'Hematologie (IUH), Universite Paris 7, for mouse housing. We also thank J Calderaro and G Morcrette for their help in additional pathological analyses. This work was supported by Grants from the Association pour la Recherche sur le Cancer (subvention fixe and funding to MP), Ligue Nationale contre le Cancer-comite Paris, Fondation Anber, Association Neurofibromatoses et Recklinghausen (to ECT and NK) and Inserm. NR 41 TC 7 Z9 7 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 5 PY 2013 VL 32 IS 36 BP 4264 EP 4272 DI 10.1038/onc.2012.436 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 214WL UT WOS:000324168000008 PM 23045274 ER PT J AU Schweier, C Hanson, JVM Funk, J Toteberg-Harms, M AF Schweier, Caterina Hanson, James V. M. Funk, Jens Toeteberg-Harms, Marc TI Repeatability of intraocular pressure measurements with Icare PRO rebound, Tono-Pen AVIA, and Goldmann tonometers in sitting and reclining positions SO BMC OPHTHALMOLOGY LA English DT Article ID DYNAMIC CONTOUR TONOMETRY; CENTRAL CORNEAL THICKNESS; APPLANATION TONOMETRY; PENETRATING KERATOPLASTIES; AGREEMENT; ACCURACY; EYES AB Background: Icare PRO (ICP) is a new Rebound tonometer that is able to measure intraocular pressure (IOP) in both sitting and reclining positions. In this study, the gold standard Goldmann tonometer (GAT) was compared to ICP and Tono-Pen AVIA (TPA). Hypothesis was that repeatability of GAT is superior to ICP and TPA. Methods: 36 eyes of 36 healthy caucasian individuals, 13 male and 26 females, 17 right and 19 left eyes have been included in this prospective, randomized, cross-sectional study. The study was conducted at a single site (Dept. of Ophthalmology, UniversityHospital Zurich, Switzerland). Primary outcome measures were Intraclass correlation coefficients (ICC) and coefficients of variation (COV) and test-retest repeatability as visualized by Bland-Altman analysis. Secondary outcome measures were IOP in sitting (GAT, ICP and TPA) and in reclining (ICP and TPA) position. Results: Mean IOP measured by GAT was 14.9 +/- 3.5 mmHg. Mean IOP measured by ICP was 15.6 +/- 3.1 mmHg (with TPA 14.8 +/- 2.7 mmHg) in sitting and 16.5 +/- 3.5 mmHg (with TPA 17.0 +/- 3.0 mmHg) in reclining positions. COVs ranged from 2.9% (GAT) to 6.9% (ICP reclining) and ICCs from 0.819 (ICP reclining) to 0.972 (GAT). Conclusions: Repeatability is good with all three devices. GAT has higher repeatability compared to the two tested hand-held devices with lowest COVs and highest ICCs. IOP was higher in the reclining compared to the sitting position. C1 [Schweier, Caterina; Hanson, James V. M.; Funk, Jens; Toeteberg-Harms, Marc] Univ Zurich Hosp, Dept Ophthalmol, CH-8091 Zurich, Switzerland. [Toeteberg-Harms, Marc] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02144 USA. RP Toteberg-Harms, M (reprint author), Univ Zurich Hosp, Dept Ophthalmol, Frauenklin Str 24, CH-8091 Zurich, Switzerland. EM MarcToeteberg@aol.com FU Swiss National Science Foundation (Bern, Switzerland) FX MT-H received personal funding by the Swiss National Science Foundation (Bern, Switzerland). NR 34 TC 7 Z9 7 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2415 J9 BMC OPHTHALMOL JI BMC Ophthalmol. PD SEP 5 PY 2013 VL 13 AR UNSP 44 DI 10.1186/1471-2415-13-44 PG 8 WC Ophthalmology SC Ophthalmology GA 214LN UT WOS:000324134900001 PM 24006952 ER PT J AU Chiu, IM Heesters, BA Ghasemlou, N Von Hehn, CA Zhao, F Tran, J Wainger, B Strominger, A Muralidharan, S Horswill, AR Wardenburg, JB Hwang, SW Carroll, MC Woolf, CJ AF Chiu, Isaac M. Heesters, Balthasar A. Ghasemlou, Nader Von Hehn, Christian A. Zhao, Fan Tran, Johnathan Wainger, Brian Strominger, Amanda Muralidharan, Sriya Horswill, Alexander R. Wardenburg, Juliane Bubeck Hwang, Sun Wook Carroll, Michael C. Woolf, Clifford J. TI Bacteria activate sensory neurons that modulate pain and inflammation SO NATURE LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; FORMYL-PEPTIDE RECEPTORS; ALPHA-HEMOLYSIN; T-CELLS; MICE; NEUTROPHILS; INFECTION; IMMUNITY; USA300; IDENTIFICATION AB Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we demonstrate that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin alpha-haemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Thus, bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation, an unsuspected role for the nervous systemin host-pathogen interactions. C1 [Chiu, Isaac M.; Ghasemlou, Nader; Von Hehn, Christian A.; Tran, Johnathan; Wainger, Brian; Strominger, Amanda; Muralidharan, Sriya; Hwang, Sun Wook; Woolf, Clifford J.] Boston Childrens Hosp, Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Chiu, Isaac M.; Ghasemlou, Nader; Von Hehn, Christian A.; Tran, Johnathan; Wainger, Brian; Strominger, Amanda; Muralidharan, Sriya; Hwang, Sun Wook; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Heesters, Balthasar A.; Carroll, Michael C.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Heesters, Balthasar A.; Carroll, Michael C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Heesters, Balthasar A.] Univ Med Ctr, NL-3584 CX Utrecht, Netherlands. [Zhao, Fan] Brandeis Univ, Dept Chem, Quantitat Biol Program, Waltham, MA 02454 USA. [Horswill, Alexander R.] Univ Iowa, Dept Microbiol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA. [Wardenburg, Juliane Bubeck] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Wardenburg, Juliane Bubeck] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA. [Hwang, Sun Wook] Korea Univ, Grad Sch Med, Seoul 136705, South Korea. RP Woolf, CJ (reprint author), Boston Childrens Hosp, Kirby Neurobiol Ctr, Boston, MA 02115 USA. EM clifford.woolf@childrens.harvard.edu RI Zhao, Fan/A-3686-2012; OI Zhao, Fan/0000-0002-6103-5608; Ghasemlou, Nader/0000-0002-1696-7342 FU NIH [PO1AI078897, 5RO1AI039246, R37NS039518, 5P01NS072040, 5F32NS076297]; FACS FX We thank L. Barrett, V. Wang, N. Andrews, C. Melin, Y. Wang, K. Duong, E. Cobos del Moral, O. Babanyi and G. Bryman for technical help. We thank Y.-C. Cheng and R. Becker for technical advice; J. Sprague and A. Yekkirala for developing whole-well imaging; I. Inoshima for recombinant alpha HL; R. Malley, J. Steen and Q. Ma for discussions; J. Chiu for moral support; S. Liberles, B. Xu and V. Kuchroo for mentoring. This work was supported by NIH PO1AI078897, 5RO1AI039246 (M. C. C.), R37NS039518, 5P01NS072040 (C. J. W.), 5F32NS076297 (I. M. C.), FACS, and microarrays at Boston Children's Hospital IDDRC facilities (NIH-P30-HD018655). NR 53 TC 116 Z9 117 U1 4 U2 95 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 5 PY 2013 VL 501 IS 7465 BP 52 EP + DI 10.1038/nature12479 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 211ER UT WOS:000323888300030 PM 23965627 ER PT J AU Dewing, S Tomlinson, M le Roux, IM Chopra, M Tsai, AC AF Dewing, Sarah Tomlinson, Mark le Roux, Ingrid M. Chopra, Mickey Tsai, Alexander C. TI Food insecurity and its association with co-occurring postnatal depression, hazardous drinking, and suicidality among women in peri-urban South Africa SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Food insecurity; Postnatal depression; Suicide; South Africa ID COMMON MENTAL-DISORDERS; SUB-SAHARAN AFRICA; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; DSM-IV; PREVALENCE; HIV/AIDS; UGANDA; RISK; VALIDATION; PREDICTORS AB Background: Although the public health impacts of food insecurity and depression on both maternal and child health are extensive, no studies have investigated the associations between food insecurity and postnatal depression or suicidality. Methods: We interviewed 249 women three months after they had given birth and assessed food insecurity, postnatal depression symptom severity, suicide risk, and hazardous drinking. Multivariable Poisson regression models with robust standard errors were used to estimate the impact of food insecurity On psychosocial outcomes. Results: Food insecurity, probable depression, and hazardous drinking were highly prevalent and co-occurring. More than half of the women (149 [59.8%]) were severely food insecure, 79 (31.7%) women met screening criteria for probable depression, and 39 (15.7%) women met screening criteria for hazardous drinking. Nineteen (7.6%) women had significant suicidality, of whom 7(2,8%) were classified as high risk. Each additional point on the food insecurity scale was associated with increased risks of probable depression (adjusted risk ratio [ARR], 1.05; 95% CI, 1.02-1.07), hazardous drinking (ARK, 1.04; 95% CI, 1.00-1.09), and suicidality (ARK, 1.12; 95% CI, 1.02-123). Evaluated at the means of the covariates, these estimated associations were large in magnitude. Limitations: The study is limited by lack of data on formal DCM-IV diagnoses of major depressive disorder, potential sample selection bias, and inability to assess the causal impact of food insecurity. Conclusion: Food insecurity is strongly associated with postnatal depression, hazardous drinking, and suicidality. Programmes promoting food security for new may enhance overall psychological well-being in addition to improving nutritional status. (C) 2013 Elsevier B.V. All rights reserved. C1 [Dewing, Sarah] Med Res Council South Africa, Hlth Syst Res Unit, Tygerberg, South Africa. [Tomlinson, Mark] Univ Stellenbosch, Dept Psychol, ZA-7600 Stellenbosch, South Africa. [Tomlinson, Mark] Univ Cape Town, Dept Psychiat & Mental Hlth, Alan J Flisher Ctr Publ Mental Hlth, ZA-7925 Cape Town, South Africa. [le Roux, Ingrid M.] Philani Child Hlth & Nutr Project, Cape Town, South Africa. [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Univ, Sch Med, Boston, MA USA. RP Tsai, AC (reprint author), MGH Ctr Global Hlth, 100 Cambridge Str,15th Floor, Boston, MA 02114 USA. EM actsai@partners.org RI Nguyen, Giang/D-9027-2016; OI Tsai, Alexander/0000-0001-6397-7917 FU Medical Research Council of South Africa; U.S. National Institutes of Health (NIH) [R25 MH-060482]; National Research Foundation (South Africa); Department for International Development (DfID-UK); NIH [K23 MH-096620]; Harvard Global Health Institute FX This study was funded by the Medical Research Council of South Africa and U.S. National Institutes of Health (NIH) R25 MH-060482. MT acknowledges the support of the National Research Foundation (South Africa) and the Department for International Development (DfID-UK). ACT acknowledges salary support from NIH K23 MH-096620 and an International Travel Fellowship Award in Support of Global Infectious Diseases Research from the Harvard Global Health Institute. NR 58 TC 20 Z9 20 U1 7 U2 34 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP 5 PY 2013 VL 150 IS 2 BP 460 EP 465 DI 10.1016/j.jad.2013.04.040 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 206YQ UT WOS:000323563300041 PM 23707034 ER PT J AU Tanenbaum, ML Ritholz, MD Binko, DH Baek, RN Shreck, MSE Gonzalez, JS AF Tanenbaum, Molly L. Ritholz, Marilyn D. Binko, Deborah H. Baek, Rachel N. Shreck, M. S. Erica Gonzalez, Jeffrey S. TI Probing for depression and finding diabetes: a mixed-methods analysis of depression interviews with adults treated for type 2 diabetes SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Diabetes; Depression; Diabetes-related distress; Screening; Comorbidity ID MONTGOMERY-ASBERG DEPRESSION; COMORBID DEPRESSION; DISTRESS SCALE; SELF-CARE; METAANALYSIS; ASSOCIATION; SYMPTOMS; PEOPLE; TEMPERAMENT; PREVALENCE AB Background: Depression has increased prevalence and consistently predicts poor health outcomes among patients with diabetes. The impact of stressors related to diabetes and its treatment on depression assessment is infrequently considered. Methods: We used mixed methods to evaluate depressive symptoms in adults with type 2 diabetes. We categorized responses related to diabetes and its treatment during interviews (n=70) using the Montgomery-Asberg Depression Rating Scale (MADRS) and administered questionnaires to measure diabetes related distress and depressive symptoms. Results: Participants (M age=56, SD=7; 67% female; 64% Black; 21% Latino) had mild depression on average (MADRS M=10, SD=9). Half of those with symptoms spontaneously mentioned diabetes context; 61% said diabetes contributed to their symptoms when questioned directly. Qualitative themes included: overlapping symptoms of diabetes and depression; burden of diabetes treatment; emotional impact of diabetes; and the bidirectional influence of depression and diabetes. Diabetes was mentioned more often at higher levels of depression severity (r=.38, p=.001). Higher HbA1c was associated with mentioning diabetes as a context for depressive symptoms (r=.32, p=.007). Insulin-users mentioned diabetes more often than those on oral medications only (p=.005). Limitations: MADRS is not a traditional qualitative interview so themes may not provide an exhaustive view of the role of diabetes context in depression assessment. Conclusions and clinical implications: The burden of type 2 diabetes and its treatment often provide an explanatory context for depressive symptoms assessed by structured clinical interviews, the gold standard of depression assessment. Diabetes context may influence accuracy of assessment and should inform intervention planning for those needing treatment. (C) 2013 Elsevier B.V. All rights reserved. C1 [Tanenbaum, Molly L.; Binko, Deborah H.; Baek, Rachel N.; Shreck, M. S. Erica; Gonzalez, Jeffrey S.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY 10461 USA. [Ritholz, Marilyn D.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ritholz, Marilyn D.] Harvard Univ, Sch Med, Boston, MA USA. [Ritholz, Marilyn D.] Boston Childrens Hosp, Boston, MA USA. [Gonzalez, Jeffrey S.] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA. RP Gonzalez, JS (reprint author), Yeshiva Univ, Ferkauf Grad Sch Psychol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jeffrey.gonzalez@einstein.yu.edu OI Tanenbaum, Molly/0000-0003-4222-4224 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-020541] FX This study was partially supported by Grant DK-020541 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NR 51 TC 3 Z9 3 U1 8 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP 5 PY 2013 VL 150 IS 2 BP 533 EP 539 DI 10.1016/j.jad.2013.01.029 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 206YQ UT WOS:000323563300051 PM 23453278 ER PT J AU Kameyama, R Inoue, T Uchida, M Tanaka, T Kitaichi, Y Nakato, Y Hayashishita, Y Nakai, Y Nakagawa, S Kusumi, I Koyama, T AF Kameyama, Rie Inoue, Takeshi Uchida, Mai Tanaka, Teruaki Kitaichi, Yuji Nakato, Yasuya Hayashishita, Yoshiyuki Nakai, Yukiei Nakagawa, Shin Kusumi, Ichiro Koyama, Tsukasa TI Development and validation of a screening questionnaire for present or past (hypo)manic episodes based on DSM-IV-TR criteria SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Manic episode screening questionnaire; Bipolar disorder; Self-report; Diagnosis; Misdiagnosis ID BIPOLAR DISORDER; SPECIFICITY; SENSITIVITY; DEPRESSION; MOOD AB Background: We developed a self-reported questionnaire, the Manic Episode Screening Questionnaire (MES), based on the eight diagnostic criteria items of DSM-IV-TR (hypo)manic episodes. This study was designed to determine the optimal screening methods to identify bipolar disorders among mood disorder patients of a psychiatric specialty clinic. Methods: In 95 mood disorder patients, we assessed the operational characteristics of the MES as a screening and diagnostic instrument using a DSM-IV-TR diagnosis by a trained psychiatrist as a reference standard. The reference criteria were bipolar disorders. MES was used with two methods: the diagnostic algorithm and the one-question method (question #1 only). The diagnostic algorithm was regarded as fulfilled if the answers to question #1 and three or more of questions #2 to #8 were "yes", corresponding to the DSM-IV-TR (hypo)manic episode criteria. In different subjects, the test-retest reliability of the MES was examined. Results: The two methods of the MES showed high specificity (0.93-0.94), high positive predictive value (0.81-0.83) and high negative predictive value (0.88-0.90), but the sensitivity scored lower (0.68-0.75). The test-retest reliability was moderate: 0.75 for the diagnostic algorithm and 0.68 for the one-question method. Limitations: This study includes a small number of bipolar l patients. The findings might not be generalized to patients outside of this patient population. Conclusions: The MES is useful for the screening and diagnosis of bipolar disorders among mood disorder patients in psychiatric specialty clinics. The one question method of the MES is more convenient to use than prior questionnaires and is here recommended. (C) 2013 Elsevier B.V. All rights reserved. C1 [Kameyama, Rie; Inoue, Takeshi; Tanaka, Teruaki; Kitaichi, Yuji; Nakato, Yasuya; Hayashishita, Yoshiyuki; Nakai, Yukiei; Nakagawa, Shin; Kusumi, Ichiro; Koyama, Tsukasa] Hokkaido Univ, Grad Sch Med, Dept Psychiat, Kita Ku, Sapporo, Hokkaido 0608638, Japan. [Uchida, Mai] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Inoue, T (reprint author), Hokkaido Univ, Grad Sch Med, Dept Psychiat, North 15,West 7, Sapporo, Hokkaido 0608638, Japan. EM tinoue@med.hokudai.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Ministry of Health, Labour and Welfare, Japan; Interdisciplinary Project for Psychosomatological Research in Hokkaido University FX This study was partly supported by "Integrated research on neuropsychiatric disorders" carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Research Grant 24-2 for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare, Japan and a grant for Interdisciplinary Project for Psychosomatological Research in Hokkaido University. NR 14 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP 5 PY 2013 VL 150 IS 2 BP 546 EP 550 DI 10.1016/j.jad.2013.01.034 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 206YQ UT WOS:000323563300053 PM 23474095 ER PT J AU Cassano, P Chang, T Trinh, NH Baer, L Fava, M Mischoulon, D AF Cassano, Paolo Chang, Trina Nhi-Ha Trinh Baer, Lee Fava, Maurizio Mischoulon, David TI Differential impact of isolated psychotic symptoms on treatment outcome of major depressive disorder in the STAR*D cohort of Whites, Blacks and Latinos SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Latinos; Hispanic; Major depressive disorder; Psychosis-like symptoms; Antidepressants; Remission ID POPULATION; AMERICAN; RACE AB Objective: To determine whether isolated psychotic symptoms are more likely to be endorsed by depressed Latinos as opposed to other ethnic-racial groups; whether these symptoms affect Latinos similarly to other ethnic-racial groups in terms of treatment response; and whether they are more likely to be associated with anxiety disorders in depressed Latinos. Methods: We analyzed data from STAR*D subjects who self identified as White, Black, or Latino. Rates of isolated psychotic symptoms were assessed by the self-rated Psychiatric Diagnostic Screening Questionnaire (PDSQ) and compared between ethnic-racial groups. Depressive remission outcomes were compared within each ethnic-racial group between subjects who endorsed psychotic symptoms versus no psychotic symptoms. Associations between isolated psychotic symptoms and anxiety disorders were also examined. Results: Among 2597 eligible subjects with at least one post-baseline assessment and available PDSQ data excluding first-rank symptoms, the prevalence of auditory-visual hallucination was 2.5% in Whites (n=49/1928), 11.3% in Blacks (n=45/398) 6.3% in Latinos (n=17/270) (chi(2)=64.9; df=2; p < 0.001). Prevalence of paranoid ideation was 15.5% in Whites (n=299/1927), 31.5% in Blacks (n-126/400), and 21.1% in Latinos (n=57/270) (chi(2)=57.3; df=2; p < 0.001). Among Whites and Blacks but not Latinos, depressive remission rates were worse in subjects with auditory-visual hallucinations compared to those without them. Paranoid ideation had a significant negative impact on remission in Whites only In all ethnic-racial groups, a significant association was found between auditory-visual hallucinations and PTSD and panic disorder. Limitations: The STAR*D study did not include any structured clinician-based assessment of psychotic symptoms. Conclusion: Latinos do not appear to have worse outcomes when treated for MDD with auditory-visual hallucinations, differently from Whites and Blacks. (C) 2013 Elsevier B.V. All rights reserved. C1 [Cassano, Paolo; Chang, Trina; Nhi-Ha Trinh; Baer, Lee; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Cassano, Paolo] North Suffolk Mental Hlth Assoc, Chelsea Counseling Ctr, Chelsea, MA 02128 USA. RP Cassano, P (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM pcassano@partners.org FU Federal funds from the National Institute of Mental Health, National Institutes of Health, Bethesda, MD [N01MH90003] FX The START project has been funded with Federal funds from the National Institute of Mental Health, National Institutes of Health, Bethesda, MD, under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (P.I.: AJ Rush). NR 23 TC 3 Z9 3 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP 5 PY 2013 VL 150 IS 2 BP 578 EP 584 DI 10.1016/j.jad.2013.02.012 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 206YQ UT WOS:000323563300058 PM 23489398 ER PT J AU Aussedat, B Vohra, Y Park, PK Fernandez-Tejada, A Alam, SM Dennison, SM Jaeger, FH Anasti, K Stewart, S Blinn, JH Liao, HX Sodroski, JG Haynes, BF Danishefsky, SJ AF Aussedat, Baptiste Vohra, Yusuf Park, Peter K. Fernandez-Tejada, Alberto Alam, S. Munir Dennison, S. Moses Jaeger, Frederick H. Anasti, Kara Stewart, Shelley Blinn, Julie H. Liao, Hua-Xin Sodroski, Joseph G. Haynes, Barton F. Danishefsky, Samuel J. TI Chemical Synthesis of Highly Congested gp120 V1V2 N-Glycopeptide Antigens for Potential HIV-1-Directed Vaccines SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODY PG9; BETA-MANNOPYRANOSIDES; LINKED GLYCOPEPTIDE; GLYCAN RECOGNITION; SULFOXIDE METHOD; HIGH-MANNOSE; CONVERGENT; HIV-1; GLYCOPROTEINS AB Critical to the search for an effective HIV-1 vaccine is the development of immunogens capable of inducing broadly neutralizing antibodies (BnAbs). A key first step in this process is to design immunogens that can be recognized by known BnAbs. The monoclonal antibody PG9 is a BnAb that neutralizes diverse strains of HIV-1 by targeting a conserved carbohydrate protein epitope in the variable 1 and 2 (V1V2) region of the viral envelope. Important for recognition are two closely spaced N-glycans at Asn(160) and Asn(156). Glycopeptides containing this synthetically challenging bis-N-glycosylated motif were prepared by convergent assembly, and were shown to be antigenic for PG9. Synthetic glycopeptides such as these may be useful for the development of HIV-1 vaccines based on the envelope V1V2 BnAb epitope. C1 [Aussedat, Baptiste; Vohra, Yusuf; Park, Peter K.; Fernandez-Tejada, Alberto; Danishefsky, Samuel J.] Sloan Kettering Inst Canc Res, Bioorgan Chem Lab, New York, NY 10065 USA. [Danishefsky, Samuel J.] Columbia Univ, Dept Chem, New York, NY 10027 USA. [Alam, S. Munir; Dennison, S. Moses; Jaeger, Frederick H.; Anasti, Kara; Stewart, Shelley; Blinn, Julie H.; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Haynes, Barton F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. [Sodroski, Joseph G.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Sodroski, Joseph G.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA. RP Danishefsky, SJ (reprint author), Sloan Kettering Inst Canc Res, Bioorgan Chem Lab, 1275 York Ave, New York, NY 10065 USA. EM s-danishefsky@ski.mskcc.org RI Fernandez-Tejada, Alberto/M-2439-2015; OI Fernandez-Tejada, Alberto/0000-0002-1680-0059; Vohra, Yusuf/0000-0003-0385-2965 FU NIH [AI 067854, AI 100645]; American Cancer Society [PF-11-014-01-CDD]; European Commission (Marie Curie International Outgoing Fellowship) FX This work was supported by NIH grants for the Center for HIV/AIDS Vaccine Immunology, AI 067854 and the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery, AI 100645. P.K.P. was supported by a postdoctoral fellowship (PF-11-014-01-CDD) from the American Cancer Society. A.F.-T, thanks the European Commission (Marie Curie International Outgoing Fellowship) for financial support. The authors thank Dr. George Sukenick, Ms. Hui Fang, and Ms. Sylvi Rusli of the NMR Analytical Core Facility at MSKCC for MS and NMR assistance. We also thank Dr. Ping Wang, Dr. Xiangyang Wu, Dr. Maciej Walczak, Dr. Gardner Creech, Dr. Steven Townsend, and Ms. Rebecca Wilson for advice and helpful discussions. We are grateful to Dr. Wayne Koff (International AIDS Vaccine Initiative, New York, NY) and Dr. Dennis Burton (The Scripps Research Institute, La Jolla, CA) for provision of mAb PG9. NR 60 TC 26 Z9 26 U1 3 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 4 PY 2013 VL 135 IS 35 BP 13113 EP 13120 DI 10.1021/ja405990z PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 296CQ UT WOS:000330163100034 PM 23915436 ER PT J AU Gaziano, JM AF Gaziano, J. Michael TI Progress With the Polypill? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CARDIOVASCULAR-DISEASE; DOUBLE-BLIND; RISK-FACTORS; TRIAL C1 [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Boston, MA 02120 USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org NR 9 TC 3 Z9 3 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 2013 VL 310 IS 9 BP 910 EP 911 DI 10.1001/jama.2013.277066 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 211DT UT WOS:000323885700018 PM 24002274 ER PT J AU Ecker, J AF Ecker, Jeffrey TI Cesarean Delivery on Maternal Request Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Ecker, Jeffrey] Harvard Univ, Sch Med, Boston, MA USA. RP Ecker, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Founders 420A, Boston, MA 02114 USA. EM jecker@partners.org NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 2013 VL 310 IS 9 BP 978 EP 979 DI 10.1001/jama.2013.194777 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 211DT UT WOS:000323885700034 PM 24002290 ER PT J AU Al-Mahdawi, S Sandi, C Pinto, RM Pook, MA AF Al-Mahdawi, Sahar Sandi, Chiranjeevi Pinto, Ricardo Mouro Pook, Mark A. TI Friedreich Ataxia Patient Tissues Exhibit Increased 5-Hydroxymethylcytosine Modification and Decreased CTCF Binding at the FXN Locus SO PLOS ONE LA English DT Article ID GAA REPEAT LENGTH; TRIPLET-REPEAT; EPIGENETIC CHANGES; DNA METHYLATION; FRATAXIN GENE; TRANSCRIPTION; BRAIN; 5-METHYLCYTOSINE; HYPEREXPANSION; EXPRESSION AB Background: Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, which induces epigenetic changes and FXN gene silencing. Bisulfite sequencing studies have identified 5-methylcytosine (5mC) DNA methylation as one of the epigenetic changes that may be involved in this process. However, analysis of samples by bisulfite sequencing is a time-consuming procedure. In addition, it has recently been shown that 5-hydroxymethylcytosine (5hmC) is also present in mammalian DNA, and bisulfite sequencing cannot distinguish between 5hmC and 5mC. Methodology/Principal Findings: We have developed specific MethylScreen restriction enzyme digestion and qPCR-based protocols to more rapidly quantify DNA methylation at four CpG sites in the FXN upstream GAA region. Increased DNA methylation was confirmed at all four CpG sites in both FRDA cerebellum and heart tissues. We have also analysed the DNA methylation status in FRDA cerebellum and heart tissues using an approach that enables distinction between 5hmC and 5mC. Our analysis reveals that the majority of DNA methylation in both FRDA and unaffected tissues actually comprises 5hmC rather than 5mC. We have also identified decreased occupancy of the chromatin insulator protein CTCF (CCCTC-binding factor) at the FXN 5' UTR region in the same FRDA cerebellum tissues. Conclusions/Significance: Increased DNA methylation at the FXN upstream GAA region, primarily 5hmC rather than 5mC, and decreased CTCF occupancy at the FXN 5' UTR are associated with FRDA disease-relevant human tissues. The role of such molecular mechanisms in FRDA pathogenesis has now to be determined. C1 [Al-Mahdawi, Sahar; Sandi, Chiranjeevi; Pook, Mark A.] Brunel Univ, Sch Hlth Sci & Social Care, Div Biosci, Ataxia Res Grp, Uxbridge UB8 3PH, Middx, England. [Pinto, Ricardo Mouro] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. RP Pook, MA (reprint author), Brunel Univ, Sch Hlth Sci & Social Care, Div Biosci, Ataxia Res Grp, Uxbridge UB8 3PH, Middx, England. EM Mark.Pook@brunel.ac.uk FU European Union [242193/EFACTS]; Wellcome Trust [089757]; Ataxia UK FX The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242193/EFACTS (CS), the Wellcome Trust [089757] (SA) and Ataxia UK (RMP) to MAP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 8 Z9 9 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 4 PY 2013 VL 8 IS 9 AR e74956 DI 10.1371/journal.pone.0074956 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219OE UT WOS:000324515600163 PM 24023969 ER PT J AU Bouatra, S Aziat, F Mandal, R Guo, AC Wilson, MR Knox, C Bjorndahl, TC Krishnamurthy, R Saleem, F Liu, P Dame, ZT Poelzer, J Huynh, J Yallou, FS Psychogios, N Dong, E Bogumil, R Roehring, C Wishart, DS AF Bouatra, Souhaila Aziat, Farid Mandal, Rupasri Guo, An Chi Wilson, Michael R. Knox, Craig Bjorndahl, Trent C. Krishnamurthy, Ramanarayan Saleem, Fozia Liu, Philip Dame, Zerihun T. Poelzer, Jenna Huynh, Jessica Yallou, Faizath S. Psychogios, Nick Dong, Edison Bogumil, Ralf Roehring, Cornelia Wishart, David S. TI The Human Urine Metabolome SO PLOS ONE LA English DT Article ID FLIGHT MASS-SPECTROMETRY; LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY; SOLID-PHASE MICROEXTRACTION; CEREBROSPINAL-FLUID METABOLOME; ORGANIC-ACIDS; NMR-SPECTROSCOPY; AMINO-ACIDS; BIOLOGICAL SAMPLES; QUANTITATIVE-ANALYSIS; BIOMARKER DISCOVERY AB Urine has long been a "favored" biofluid among metabolomics researchers. It is sterile, easy-to-obtain in large volumes, largely free from interfering proteins or lipids and chemically complex. However, this chemical complexity has also made urine a particularly difficult substrate to fully understand. As a biological waste material, urine typically contains metabolic breakdown products from a wide range of foods, drinks, drugs, environmental contaminants, endogenous waste metabolites and bacterial by-products. Many of these compounds are poorly characterized and poorly understood. In an effort to improve our understanding of this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide characterization of human urine. This involved both computer-aided literature mining and comprehensive, quantitative experimental assessment/validation. The experimental portion employed NMR spectroscopy, gas chromatography mass spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS), inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) experiments performed on multiple human urine samples. This multi-platform metabolomic analysis allowed us to identify 445 and quantify 378 unique urine metabolites or metabolite species. The different analytical platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85) by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our use of multiple metabolomics platforms and technologies allowed us to identify several previously unknown urine metabolites and to substantially enhance the level of metabolome coverage. It also allowed us to critically assess the relative strengths and weaknesses of different platforms or technologies. The literature review led to the identification and annotation of another 2206 urinary compounds and was used to help guide the subsequent experimental studies. An online database containing the complete set of 2651 confirmed human urine metabolite species, their structures (3079 in total), concentrations, related literature references and links to their known disease associations are freely available at http://www.urinemetabolome.ca. C1 [Bouatra, Souhaila; Aziat, Farid; Mandal, Rupasri; Bjorndahl, Trent C.; Krishnamurthy, Ramanarayan; Saleem, Fozia; Liu, Philip; Dame, Zerihun T.; Poelzer, Jenna; Huynh, Jessica; Yallou, Faizath S.; Dong, Edison; Wishart, David S.] Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. [Guo, An Chi; Wilson, Michael R.; Knox, Craig; Wishart, David S.] Univ Alberta, Dept Comp Sci, Edmonton, AB, Canada. [Psychogios, Nick] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Bogumil, Ralf; Roehring, Cornelia] BIOCRATES Life Sci AG, Innsbruck, Austria. [Wishart, David S.] Natl Inst Nanotechnol, Edmonton, AB, Canada. RP Wishart, DS (reprint author), Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. EM david.wishart@ualberta.ca OI Psychogios, Nikolaos/0000-0002-2747-6012; Wishart, David S/0000-0002-3207-2434 FU Genome Canada; Genome Alberta; Canadian Institutes of Health Research; Alberta Innovates BioSolutions; Alberta Innovates Health Solutions; National Research Council; National Institute of Nanotechnology FX Funding for this research has been provided by Genome Canada, Genome Alberta, The Canadian Institutes of Health Research, Alberta Innovates BioSolutions, Alberta Innovates Health Solutions, The National Research Council, The National Institute of Nanotechnology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 120 TC 161 Z9 162 U1 24 U2 251 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 4 PY 2013 VL 8 IS 9 AR e73076 DI 10.1371/journal.pone.0073076 PG 28 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219OE UT WOS:000324515600066 PM 24023812 ER PT J AU Peng, ZC Zhang, NH Wei, WZ Huang, CS Cetina, Y Otis, TS Houser, CR AF Peng, Zechun Zhang, Nianhui Wei, Weizheng Huang, Christine S. Cetina, Yliana Otis, Thomas S. Houser, Carolyn R. TI A Reorganized GABAergic Circuit in a Model of Epilepsy: Evidence from Optogenetic Labeling and Stimulation of Somatostatin Interneurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID TEMPORAL-LOBE EPILEPSY; KAINATE-TREATED RATS; SPONTANEOUS RECURRENT SEIZURES; FIBER SYNAPTIC REORGANIZATION; PILOCARPINE-INDUCED SEIZURES; CA1 PYRAMIDAL CELLS; DENTATE GYRUS; MOUSE MODEL; GRANULE CELLS; FASCIA-DENTATA AB Axonal sprouting of excitatory neurons is frequently observed in temporal lobe epilepsy, but the extent to which inhibitory interneurons undergo similar axonal reorganization remains unclear. The goal of this study was to determine whether somatostatin (SOM)-expressing neurons in stratum (s.) oriens of the hippocampus exhibit axonal sprouting beyond their normal territory and innervate granule cells of the dentate gyrus in a pilocarpine model of epilepsy. To obtain selective labeling of SOM-expressing neurons in s. oriens, a Cre recombinase-dependent construct for channelrhodopsin2 fused to enhanced yellow fluorescent protein (ChR2-eYFP) was virally delivered to this region in SOM-Cre mice. In control mice, labeled axons were restricted primarily to s. lacunosum-moleculare. However, in pilocarpine-treated animals, a rich plexus of ChR2-eYFP-labeled fibers and boutons extended into the dentate molecular layer. Electron microscopy with immunogold labeling demonstrated labeled axon terminals that formed symmetric synapses on dendritic profiles in this region, consistent with innervation of granule cells. Patterned illumination of ChR2-labeled fibers in s. lacunosum-moleculare of CA1 and the dentate molecular layer elicited GABAergic inhibitory responses in dentate granule cells in pilocarpine-treated mice but not in controls. Similar optical stimulation in the dentate hilus evoked no significant responses in granule cells of either group of mice. These findings indicate that under pathological conditions, SOM/GABAergic neurons can undergo substantial axonal reorganization beyond their normal territory and establish aberrant synaptic connections. Such reorganized circuitry could contribute to functional deficits in inhibition in epilepsy, despite the presence of numerous GABAergic terminals in the region. C1 [Peng, Zechun; Zhang, Nianhui; Huang, Christine S.; Cetina, Yliana; Otis, Thomas S.; Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Wei, Weizheng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Otis, Thomas S.; Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, CHS 73-235,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU National Institutes of Health [NS075245, RR029267, NS068408]; Veterans Affairs Medical Research Funds FX This work was supported by National Institutes of Health Grants NS075245 (C. R. H.), RR029267 (T.S.O.), and NS068408 (T.S.O.) and Veterans Affairs Medical Research Funds (C. R. H.). We gratefully acknowledge Dr. Karl Deisseroth for making reagents available through Addgene and the Penn Vector Core in the School of Medicine Gene Therapy Program at the University of Pennsylvania for preparation of the viral vector. We thank Dr. Istvan Mody for helpful discussions. NR 61 TC 29 Z9 29 U1 1 U2 28 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 4 PY 2013 VL 33 IS 36 BP 14392 EP 14405 DI 10.1523/JNEUROSCI.2045-13.2013 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 214VQ UT WOS:000324165500013 PM 24005292 ER PT J AU Castiblanco, J Arcos-Burgos, M Anaya, JM AF Castiblanco, John Arcos-Burgos, Mauricio Anaya, Juan-Manuel TI What is next after the genes for autoimmunity? SO BMC MEDICINE LA English DT Review DE Autoimmunity; Common; Genetics; Genomics; Personalized; Predictive medicine; Polyautoimmunity; Translational medicine ID GENOME-WIDE ASSOCIATION; DISEASE GENETICS; MEDICINE; MECHANISMS; BIOINFORMATICS; HERITABILITY; ENVIRONMENT; MICROBIOME; EXPRESSION; DISORDERS AB Clinical pathologies draw us to envisage disease as either an independent entity or a diverse set of traits governed by common physiopathological mechanisms, prompted by environmental assaults throughout life. Autoimmune diseases are not an exception, given they represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. Although they are pleiotropic outcomes of non-specific disease genes underlying similar immunogenetic mechanisms, research generally focuses on a single disease. Drastic technologic advances are leading research to organize clinical genomic multidisciplinary approaches to decipher the nature of human biological systems. Once the currently costly omic-based technologies become universally accessible, the way will be paved for a cleaner picture to risk quantification, prevention, prognosis and diagnosis, allowing us to clearly define better phenotypes always ensuring the integrity of the individuals studied. However, making accurate predictions for most autoimmune diseases is an ambitious challenge, since the understanding of these pathologies is far from complete. Herein, some pitfalls and challenges of the genetics of autoimmune diseases are reviewed, and an approximation to the future of research in this field is presented. C1 [Castiblanco, John; Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res CREA, Sch Med & Hlth Sci, Bogota, Colombia. [Castiblanco, John] Univ Rosario, Doctoral Program Biomed Sci, Bogota, Colombia. [Castiblanco, John] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX 78229 USA. [Castiblanco, John] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Arcos-Burgos, Mauricio] Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, ANU Coll Med Biol & Environm, Canberra, ACT 2601, Australia. RP Anaya, JM (reprint author), Univ Rosario, Ctr Autoimmune Dis Res CREA, Sch Med & Hlth Sci, Carrera 24 63-C-69, Bogota, Colombia. EM juan.anaya@urosario.edu.co RI CASTIBLANCO, JOHN/B-6599-2009; Anaya, Juan-Manuel/J-1960-2016; OI CASTIBLANCO, JOHN/0000-0002-7965-9822; Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392 FU Universidad del Rosario; Colciencias, Bogota, Colombia [122254531722] FX This work was supported by Universidad del Rosario and Colciencias (122254531722), Bogota, Colombia. NR 60 TC 10 Z9 10 U1 0 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD SEP 4 PY 2013 VL 11 AR 197 DI 10.1186/1741-7015-11-197 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 211KM UT WOS:000323905900001 PM 24107170 ER PT J AU Bruinsma, WE Guitton, TG Warner, JJP Ring, D AF Bruinsma, Wendy E. Guitton, Thierry G. Warner, Jon J. P. Ring, David CA Sci Variation Grp TI Interobserver Reliability of Classification and Characterization of Proximal Humeral Fractures A Comparison of Two and Three-Dimensional CT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NEER-CLASSIFICATION; REPRODUCIBILITY; AGREEMENT; OBSERVER; DOCTORS; SYSTEM AB Background: Interobserver reliability for the classification of proximal humeral fractures is limited. The aim of this study was to test the null hypothesis that interobserver reliability of the AO classification of proximal humeral fractures, the preferred treatment, and fracture characteristics is the same for two-dimensional (2-D) and three-dimensional (3-D) computed tomography (CT). Methods: Members of the Science of Variation Group-fully trained practicing orthopaedic and trauma surgeons from around the world-were randomized to evaluate radiographs and either 2-D CT or 3-D CT images of fifteen proximal humeral fractures via a web-based survey and respond to the following four questions: (1) Is the greater tuberosity displaced? (2) Is the humeral head split? (3) Is the arterial supply compromised? (4) Is the glenohumeral joint dislocated? They also classified the fracture according to the AO system and indicated their preferred treatment of the fracture (operative or nonoperative). Agreement among observers was assessed with use of the multirater kappa (kappa) measure. Results: Interobserver reliability of the AO classification, fracture characteristics, and preferred treatment generally ranged from "slight" to "fair." A few small but statistically significant differences were found. Observers randomized to the 2-D CT group had slightly but significantly better agreement on displacement of the greater tuberosity (kappa = 0.35 compared with 0.30, p < 0.001) and on the AO classification (kappa = 0.18 compared with 0.17, p = 0.018). A subgroup analysis of the AO classification results revealed that shoulder and elbow surgeons, orthopaedic trauma surgeons, and surgeons in the United States had slightly greater reliability on 2-D CT, whereas surgeons in practice for ten years or less and surgeons from other subspecialties had slightly greater reliability on 3-D CT. Conclusions: Proximal humeral fracture classifications may be helpful conceptually, but they have poor interobserver reliability even when 3-D rather than 2-D CT is utilized. This may contribute to the similarly poor interobserver reliability that was observed for selection of the treatment for proximal humeral fractures. The lack of a reliable classification confounds efforts to compare the outcomes of treatment methods among different clinical trials and reports. C1 [Bruinsma, Wendy E.; Guitton, Thierry G.; Warner, Jon J. P.; Ring, David; Sci Variation Grp] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bruinsma, WE (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Borris, Lars/0000-0002-0527-1518; Frihagen, Frede/0000-0002-4811-669X; Guitton, Thierry/0000-0002-2599-1985 NR 19 TC 19 Z9 19 U1 0 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP 4 PY 2013 VL 95A IS 17 BP 1600 EP 1604 DI 10.2106/JBJS.L.00586 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 210VR UT WOS:000323863300011 PM 24005201 ER PT J AU Ji, MB Orringer, DA Freudiger, CW Ramkissoon, S Liu, XH Lau, D Golby, AJ Norton, I Hayashi, M Agar, NYR Young, GS Spino, C Santagata, S Camelo-Piragua, S Ligon, KL Sagher, O Xie, XS AF Ji, Minbiao Orringer, Daniel A. Freudiger, Christian W. Ramkissoon, Shakti Liu, Xiaohui Lau, Darryl Golby, Alexandra J. Norton, Isaiah Hayashi, Marika Agar, Nathalie Y. R. Young, Geoffrey S. Spino, Cathie Santagata, Sandro Camelo-Piragua, Sandra Ligon, Keith L. Sagher, Oren Xie, X. Sunney TI Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID MALIGNANT GLIOMA; IN-VIVO; MOUSE-BRAIN; GENERATION MICROSCOPY; CARS MICROSCOPY; RESECTION; SURGERY; TISSUE; EXTENT; SENSITIVITY AB Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. We describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from nonneoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and hematoxylin and eosin microscopy for detection of glioma infiltration (kappa = 0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct. C1 [Ji, Minbiao; Freudiger, Christian W.; Xie, X. Sunney] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Orringer, Daniel A.; Lau, Darryl; Sagher, Oren] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Ramkissoon, Shakti; Santagata, Sandro; Ligon, Keith L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ramkissoon, Shakti; Hayashi, Marika; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Liu, Xiaohui; Golby, Alexandra J.; Norton, Isaiah; Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Golby, Alexandra J.; Agar, Nathalie Y. R.; Young, Geoffrey S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Spino, Cathie] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Camelo-Piragua, Sandra] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Ligon, Keith L.] Harvard Univ, Dept Pathol, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Xie, XS (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM xie@chemistry.harvard.edu RI Ji, Minbiao/C-7793-2011 OI Ji, Minbiao/0000-0002-9066-4008 FU NIH [1R01EB010244-01, R25CA089017, P01CA095616] FX This work was supported by the NIH Director's Transformative Research Award Program T-R01 (1R01EB010244-01 to X.S.X.) and NIH grants R25CA089017 (to D.A.O.) and P01CA095616 (K.L.L.). NR 39 TC 99 Z9 100 U1 7 U2 48 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD SEP 4 PY 2013 VL 5 IS 201 AR 201ra119 DI 10.1126/scitranslmed.3005954 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 214WJ UT WOS:000324167800006 PM 24005159 ER PT J AU Sorond, FA Hurwitz, S Salat, DH Greve, DN Fisher, NDL AF Sorond, Farzaneh A. Hurwitz, Shelley Salat, David H. Greve, Douglas N. Fisher, Naomi D. L. TI Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; NORMAL BRAIN; BLOOD-FLOW AB Objective: To investigate the relationship between neurovascular coupling and cognitive function in elderly individuals with vascular risk factors and to determine whether neurovascular coupling could be modified by cocoa consumption. Methods: Sixty older people (aged 72.9 +/- 5.4 years) were studied in a parallel-arm, double-blind clinical trial of neurovascular coupling and cognition in response to 24 hours and 30 days of cocoa consumption. Cognitive measures included Mini-Mental State Examination and Trail Making Test A and B. Neurovascular coupling was measured from the beat-to-beat blood flow velocity responses in the middle cerebral arteries to the N-Back Task. In a subset of MRI-eligible participants, cerebral white matter structural integrity was also measured. Results: Neurovascular coupling was associated with Trails B scores (p = 0.002) and performance on the 2-Back Task. Higher neurovascular coupling was also associated with significantly higher fractional anisotropy in cerebral white matter hyperintensities (p = 0.02). Finally, 30 days of cocoa consumption was associated with increased neurovascular coupling (5.6% +/- 7.2% vs 22.4% +/- 4.8%; p = 0.001) and improved Trails B times (116 +/- 78 seconds vs 167 +/- 110 seconds; p = 0.007) in those with impaired neurovascular coupling at baseline. Conclusion: There is a strong correlation between neurovascular coupling and cognitive function, and both can be improved by regular cocoa consumption in individuals with baseline impairments. Better neurovascular coupling is also associated with greater white matter structural integrity. C1 [Sorond, Farzaneh A.] Brigham & Womens Hosp, Dept Neurol, Stroke Div, Boston, MA 02115 USA. [Hurwitz, Shelley; Fisher, Naomi D. L.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Salat, David H.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Salat, David H.; Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02114 USA. [Sorond, Farzaneh A.; Hurwitz, Shelley; Salat, David H.; Greve, Douglas N.; Fisher, Naomi D. L.] Harvard Univ, Sch Med, Boston, MA USA. RP Sorond, FA (reprint author), Brigham & Womens Hosp, Dept Neurol, Stroke Div, 75 Francis St, Boston, MA 02115 USA. EM fsorond@partners.org FU National Institute on Aging [K23-AG030967]; National Heart, Lung, and Blood Institute, Bethesda, MD [RO1HL089570] FX Supported by grants K23-AG030967 (F. A. S.) from the National Institute on Aging, and RO1HL089570 (N.D.L.F.) from the National Heart, Lung, and Blood Institute, Bethesda, MD. Cocoa was provided by Mars Inc. NR 19 TC 19 Z9 19 U1 3 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 3 PY 2013 VL 81 IS 10 BP 904 EP 909 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AA0EF UT WOS:000330767400013 PM 23925758 ER PT J AU Brinkman, TM Zhu, L Zeltzer, LK Recklitis, CJ Kimberg, C Zhang, N Muriel, AC Stovall, M Srivastava, DK Robison, LL Krull, KR AF Brinkman, T. M. Zhu, L. Zeltzer, L. K. Recklitis, C. J. Kimberg, C. Zhang, N. Muriel, A. C. Stovall, M. Srivastava, D. K. Robison, L. L. Krull, K. R. TI Longitudinal patterns of psychological distress in adult survivors of childhood cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE psychological distress; survivorship; childhood cancer ID LONG-TERM SURVIVORS; BRIEF SYMPTOM INVENTORY-18; DEPRESSIVE SYMPTOMS; SPECIALISTS; RESOURCE; IDEATION; OUTCOMES; THERAPY; LIFE AB Background: This study investigated longitudinal patterns of psychological distress in adult survivors of childhood cancer. Methods: Participants included 4569 adult survivors in the Childhood Cancer Survivor Study Cohort (CCSS) who completed the Brief Symptom Inventory-18 on three occasions between 1994 and 2010. Longitudinal latent class analysis was used to identify discrete classes of psychological distress. Predictors of class membership were examined through logistic regression modelling with odds ratios (ORs) and 95% confidence intervals (CIs) reported. Results: Survivors were a median of 39 years of age and 30 years from diagnosis at the most recent follow-up. Most survivors reported few or no symptoms of distress over time, although subsets of survivors reported persistently elevated (depression: 8.9%; anxiety: 4.8%; somatisation: 7.2%) or significant increases in distress symptoms over the follow-up period (depression: 10.2%; anxiety: 11.8%; somatisation: 13.0%). Increasing distress symptoms were predicted by survivor perception of worsening physical health over time (depression: OR=3.3; 95% CI=2.4-4.5; anxiety: OR=3.0; 95% CI=2.2-4.0; somatisation: OR=5.3; 95% CI=3.9-7.4). Persistent distress symptoms were also predicted by survivor perception of worsening physical health over time, as well as by worsening pain and ending analgesic use. Conclusion: Subgroups of adult survivors are at-risk for chronic distress or significant increases in distress decades following their original cancer diagnosis. Routine screening of psychological distress in adult survivors of childhood cancer is warranted, especially for survivors who experience physical health morbidities. C1 [Brinkman, T. M.; Kimberg, C.; Robison, L. L.; Krull, K. R.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Zhu, L.; Zhang, N.; Srivastava, D. K.] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Zeltzer, L. K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Recklitis, C. J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02215 USA. [Muriel, A. C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Stovall, M.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Brinkman, TM (reprint author), St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM tara.brinkman@stjude.org FU National Cancer Institute [U24 CA 055727]; Cancer Center Support (CORE) grant [CA21765]; ALSAC FX This work was supported by grant U24 CA 055727 (LLR) from the National Cancer Institute, with additional support provided to St Jude Children's Research Hospital by the Cancer Center Support (CORE) grant CA21765 and by ALSAC. NR 31 TC 20 Z9 20 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 3 PY 2013 VL 109 IS 5 BP 1373 EP 1381 DI 10.1038/bjc.2013.428 PG 9 WC Oncology SC Oncology GA 214WP UT WOS:000324168500038 PM 23880828 ER PT J AU Farsani, TT Kore, S Nadol, P Ramam, M Thierman, SJ Leslie, K Chandrasekar, C Sikhamani, R Manoharan, G Kubba, A Maurer, TA AF Farsani, Terry T. Kore, Sachin Nadol, Patrick Ramam, Mandalaparthy Thierman, Sara J. Leslie, Kieron Chandrasekar, Chockalingam Sikhamani, Rajasekaran Manoharan, Gurusamy Kubba, Asha Maurer, Toby A. TI Etiology and risk factors associated with a pruritic papular eruption in people living with HIV in India SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY LA English DT Article DE papulopruritic eruption; dermatologic; skin; AIDS; HIV; CD4; eosinophilic folliculitis ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 LYMPHOCYTE COUNTS; INFECTED PATIENTS; DISEASE; MANIFESTATIONS; DISORDERS; SPECTRUM; ZAMBIA AB Introduction: Papulopruritic eruption (PPE) occurs in people living with HIV in India. Understanding the risk factors associated with this disease may help decrease the prevalence of PPE. Methods: This study was a case-control study performed at the Government Hospital of Thoracic Medicine, a tertiary care hospital in Chennai, India. Cases included HIV-positive, antiretroviral (ARV) therapy-naive adults experiencing a pruritic skin eruption for longer than one month, with evidence of multiple papular or nodular lesions and biopsy consistent with arthropod bite. Controls included HIV-positive, ARV-naive patients without active skin rash. Main outcome measures were CD4 cell count, histology, and environmental exposures. We performed statistical analysis using Epi Info version 3.5.1 and SPSS version 11.0 (SPSS Inc., Chicago, IL). Categorical variables such as gender, urban versus rural residence, occupation, treatment history, CD4 count, use of insect repellents, and environmental exposures were evaluated using the chi(2) test (or the Fisher exact test when an expected value for a category was less than 5). The t-test was used to evaluate differences in age and the duration since HIV diagnosis. The Mann-Whitney test was used to compare non-normally distributed values such as CD4 cell count. A p-value that was less than 0.05 was considered to be statistically significant. Results: Forty-one cases and 149 control subjects were included. Subjects with PPE had significantly lower CD4 cell counts compared to controls (225.5 cells/mu L vs. 425 cells/mL; p = 0.0001). Sixty-six percent of cases had a CD4 cell count less than 350 cells/mu L. PPE cases were less likely to use mosquito repellent techniques (odds ratio 2.81, CI = 1.45-5.45). Discussion: PPE may be an altered and exaggerated immune response to arthropod bites in HIV-positive patients. CD4 cell count is significantly lower in patients with PPE, and therefore it may be considered a qualifying clinical finding for ARV initiation in resource-poor settings. Protective measures against mosquito bites appeared to be important in preventing PPE in subjects at risk. C1 [Farsani, Terry T.] Harvard Univ, Sch Med, Boston, MA USA. [Kore, Sachin] Govt Hosp Thorac Med, Madras, Tamil Nadu, India. [Nadol, Patrick; Chandrasekar, Chockalingam; Sikhamani, Rajasekaran; Manoharan, Gurusamy] Int Training & Educ Ctr HIV Itech, Madras, Tamil Nadu, India. [Ramam, Mandalaparthy; Kubba, Asha] All India Inst Med Sci, New Delhi, India. [Thierman, Sara J.] Suny Downstate Med Ctr, Dept Dermatol, New York, NY USA. [Leslie, Kieron; Maurer, Toby A.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Farsani, TT (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 616,55 Fruit St, Boston, MA 02114 USA. EM tfarsani@gmail.com NR 25 TC 1 Z9 1 U1 1 U2 4 PU INT AIDS SOCIETY PI GENEVA PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND SN 1758-2652 J9 J INT AIDS SOC JI J. Int. AIDS Soc. PD SEP 3 PY 2013 VL 16 AR 17325 DI 10.7448/IAS.16.1.17325 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 214VN UT WOS:000324165200001 PM 24004854 ER PT J AU Yi, CL Shen, ZW Stemmer-Rachamimov, A Dawany, N Troutman, S Showe, LC Liu, Q Shimono, A Sudol, M Holmgren, L Stanger, BZ Kissil, JL AF Yi, Chunling Shen, Zhewei Stemmer-Rachamimov, Anat Dawany, Noor Troutman, Scott Showe, Louise C. Liu, Qin Shimono, Akihiko Sudol, Marius Holmgren, Lars Stanger, Ben Z. Kissil, Joseph L. TI The p130 Isoform of Angiomotin Is Required for Yap-Mediated Hepatic Epithelial Cell Proliferation and Tumorigenesis SO SCIENCE SIGNALING LA English DT Article ID ORGAN SIZE CONTROL; HIPPO PATHWAY; TUMOR-SUPPRESSOR; CONTACT INHIBITION; ENDOTHELIAL-CELLS; GROWTH-CONTROL; IN-VIVO; PROTEIN; ANGIOGENESIS; MIGRATION AB The Hippo-Yap signaling pathway regulates a number of developmental and adult cellular processes, including cell fate determination, tissue growth, and tumorigenesis. Members of the scaffold protein angiomotin (Amot) family interact with several Hippo pathway components, including Yap (Yes-associated protein), and either stimulate or inhibit Yap activity. We used a combination of genetic, biochemical, and transcriptional approaches to assess the functional consequences of the Amot-Yap interaction in mice and in human cells. Mice with a liver-specific Amot knockout exhibited reduced hepatic "oval cell" proliferation and tumorigenesis in response to toxin-induced injury or when crossed with mice lacking the tumor suppressor Nf2. Biochemical examination of the Amot-Yap interaction revealed that the p130 splicing isoform of Amot (Amot-p130) and Yap interacted in both the cytoplasm and nucleus, which involved binding of PPxY and LPxY motifs in Amot-p130 to WW domains of Yap. In the cytoplasm, Amot-p130 prevented the phosphorylation of Yap by blocking access of the WW domains to the kinase Lats1. Within the nucleus, Amot-p130 was associated with the transcriptional complex containing Yap and Teads (TEA domain family members) and contributed to the regulation of a subset of Yap target genes, many of which are associated with tumorigenesis. These findings indicated that Amot acts as a Yap cofactor, preventing Yap phosphorylation and augmenting its activity toward a specific set of genes that facilitate tumorigenesis. C1 [Yi, Chunling] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Mol Oncol Program, Washington, DC 20057 USA. [Shen, Zhewei; Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Div Gastroenterol,Dept Med, Philadelphia, PA 19104 USA. [Shen, Zhewei; Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dawany, Noor; Showe, Louise C.; Liu, Qin] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Troutman, Scott; Kissil, Joseph L.] Scripps Inst, Dept Canc Biol, Jupiter, FL 33458 USA. [Shimono, Akihiko] TransGenic Inc, Chuo Ku, Kobe, Hyogo 6500047, Japan. [Sudol, Marius] Weis Ctr Res, Geisinger Clin, Danville, PA 17821 USA. [Sudol, Marius] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Holmgren, Lars] Karolinska Inst, Dept Pathol & Oncol, SE-17176 Stockholm, Sweden. RP Kissil, JL (reprint author), Scripps Inst, Dept Canc Biol, Jupiter, FL 33458 USA. EM cy232@georgetown.edu; bstanger@exchange.upenn.edu; jkissil@scripps.edu FU NIH [DK083355, DK083111, CA142295, NS077952, CA0180815, CA132098]; Commonwealth of Pennsylvania [66651-01]; PA Breast Cancer Coalition [60707, 920093]; Abramson Family Cancer Research Institute; Geisinger Clinic; Pew Charitable Trusts; Children's Tumor Foundation; Georgetown Lombardi Cancer Center; Cell and Molecular Biology training grant [GM 07229-35]; Cancer Center Support Grant [CA051008] FX This work was supported in part by the NIH (DK083355 and DK083111 to B.Z.S., CA142295 and NS077952 to J. L. K., and CA0180815 and CA132098 to L. C. S.), the Commonwealth of Pennsylvania (66651-01 to L. C. S.), the PA Breast Cancer Coalition (60707 and 920093 to M. S.), the Abramson Family Cancer Research Institute, the Geisinger Clinic, and the Pew Charitable Trusts. C.Y. was a recipient of a Young Investigator Award from the Children's Tumor Foundation and is currently supported by a Georgetown Lombardi Cancer Center new faculty startup fund. Z.S. was a recipient of the Cell and Molecular Biology training grant (GM 07229-35). We are thankful for the help from Lombardi Cancer Center tissue culture and microscopy core facilities supported by Cancer Center Support Grant CA051008. NR 46 TC 49 Z9 49 U1 1 U2 22 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 J9 SCI SIGNAL JI Sci. Signal. PD SEP 3 PY 2013 VL 6 IS 291 AR ra77 DI 10.1126/scisignal.2004060 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213VZ UT WOS:000324089800003 PM 24003254 ER PT J AU Deswal, A Basra, SS AF Deswal, Anita Basra, Sukhdeep S. TI Incident Cancer in Patients With Heart Failure Causation or Mere Association? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE cancer; epidemiology; follow-up studies; heart failure; risk C1 [Deswal, Anita] Michael E DeBakey VAMC, Sect Cardiol, Houston, TX USA. [Deswal, Anita; Basra, Sukhdeep S.] Baylor Coll Med, Cardiol Sect, Houston, TX 77030 USA. RP Deswal, A (reprint author), Michael E DeBakey VA Med Ctr 111B, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM adeswal@bcm.edu NR 10 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 3 PY 2013 VL 62 IS 10 BP 887 EP 888 DI 10.1016/j.jacc.2013.04.087 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 211IO UT WOS:000323900300006 PM 23810872 ER PT J AU Tawakol, A Fayad, ZA Mogg, R Alon, A Klimas, MT Dansky, H Subramanian, SS Abdelbaky, A Rudd, JHF Farkouh, ME Nunes, IO Beals, CR Shankar, SS AF Tawakol, Ahmed Fayad, Zahi A. Mogg, Robin Alon, Achilles Klimas, Michael T. Dansky, Hayes Subramanian, Sharath S. Abdelbaky, Amr Rudd, James H. F. Farkouh, Michael E. Nunes, Irene O. Beals, Chan R. Shankar, Sudha S. TI Intensification of Statin Therapy Results in a Rapid Reduction in Atherosclerotic Inflammation Results of a Multicenter Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Feasibility Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atherosclerosis; atorvastatin; FDG; inflammation; plaque; statins ID ACUTE CORONARY SYNDROMES; PLAQUE INFLAMMATION; CARDIOVASCULAR EVENTS; ACTIVATED MACROPHAGES; VASCULAR INFLAMMATION; FDG-PET; ATORVASTATIN; DISEASE; PREVENTION; EFFICACY AB Objectives The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT). Background Intensification of statin therapy reduces major cardiovascular events. Methods Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment. Results Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p < 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [-2.3% to 10.4%]; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes. Conclusions Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261) (C) 2013 by the American College of Cardiology Foundation C1 [Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Tawakol, Ahmed; Subramanian, Sharath S.; Abdelbaky, Amr] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Tawakol, Ahmed; Subramanian, Sharath S.; Abdelbaky, Amr] Harvard Univ, Sch Med, Boston, MA USA. [Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY USA. [Fayad, Zahi A.] Mt Sinai Sch Med, Dept Radiol, New York, NY USA. [Fayad, Zahi A.; Farkouh, Michael E.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY USA. [Mogg, Robin; Alon, Achilles; Klimas, Michael T.; Dansky, Hayes; Nunes, Irene O.; Beals, Chan R.; Shankar, Sudha S.] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Farkouh, Michael E.] Univ Toronto, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Farkouh, Michael E.] Univ Toronto, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org OI Rudd, James/0000-0003-2243-3117 FU Merck Sharp & Dohme Corporation, a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey FX The authors acknowledge the following investigators and sites for clinical and imaging assistance: Jacqueline Brunetti, MD, Nathaniel Lebowitz, MD, Holy Name Medical Center, Department of Radiology, Teaneck, New Jersey; Neil J. Fraser, MD, FACP, Troy Internal Medicine Research, Troy, Michigan; Peter A. McCullough, MD, Ching Yee Wong, MD, William Beaumont Hospital, Beaumont Health Center, Royal Oak, Michigan; Brooke J Nevins, MD, Bronxville, NY; Eli M. Roth, MD, FACC, CPI, Sterling Research Group, Ltd., Cincinnati, Ohio; James M. Rhyne, MD, Lipid Center, Statesville, North Carolina; Joel Rubenstein, MD, Newton-Wellesley Cardiology, Newton, Massachusetts; Cezar S. Staniloae, MD, Gotham Cariovascular Research, PC, New York, New York. Editorial assistance was provided by Wendy Horn, PhD, of Insight Communications Group, Westfield, New Jersey. This assistance was funded by Merck Sharp & Dohme Corporation, a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey. NR 30 TC 102 Z9 103 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 3 PY 2013 VL 62 IS 10 BP 909 EP 917 DI 10.1016/j.jacc.2013.04.066 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 211IO UT WOS:000323900300010 PM 23727083 ER PT J AU Britton, KA Massaro, JM Murabito, JM Kreger, BE Hoffmann, U Fox, CS AF Britton, Kathryn A. Massaro, Joseph M. Murabito, Joanne M. Kreger, Bernard E. Hoffmann, Udo Fox, Caroline S. TI Body Fat Distribution, Incident Cardiovascular Disease, Cancer, and All-Cause Mortality SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE body fat distribution; cancer; cardiovascular disease; obesity; visceral fat ID VISCERAL ADIPOSE-TISSUE; PERICARDIAL FAT; ABDOMINAL FAT; RISK-FACTORS; ASSOCIATION; OBESITY; INFLAMMATION; BURDEN; MEN AB Objectives The aim of this study was to determine whether ectopic fat depots are prospectively associated with cardiovascular disease, cancer, and all-cause mortality. Background The morbidity associated with excess body weight varies among individuals of similar body mass index. Ectopic fat depots may underlie this risk differential. However, prospective studies of directly measured fat are limited. Methods Participants from the Framingham Heart Study (n = 3,086; 49% women; mean age of 50.2 years) underwent assessment of fat depots (visceral adipose tissue, pericardial adipose tissue, and periaortic adipose tissue) using multidetector computed tomography and were followed up longitudinally for a median of 5.0 years. Cox proportional hazards regression models were used to examine the association of each fat depot (per 1 SD increment) with the risk of incident cardiovascular disease, cancer, and all-cause mortality after adjustment for standard risk factors, including body mass index. Results Overall, there were 90 cardiovascular events, 141 cancer events, and 71 deaths. After multivariable adjustment, visceral adipose tissue was associated with cardiovascular disease (hazard ratio: 1.44; 95% confidence interval: 1.08 to 1.92; p = 0.01) and cancer (hazard ratio: 1.43; 95% confidence interval: 1.12 to 1.84; p = 0.005). Addition of visceral adipose tissue to a multivariable model that included body mass index modestly improved cardiovascular risk prediction (net reclassification improvement of 16.3%). None of the fat depots were associated with all-cause mortality. Conclusions Visceral adiposity is associated with incident cardiovascular disease and cancer after adjustment for clinical risk factors and generalized adiposity. These findings support the growing appreciation of a pathogenic role of ectopic fat. (C) 2013 by the American College of Cardiology Foundation C1 [Britton, Kathryn A.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Britton, Kathryn A.; Murabito, Joanne M.; Kreger, Bernard E.; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Murabito, Joanne M.; Kreger, Bernard E.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fox, Caroline S.] NHLBI, Framingham, MA USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Hypertens, Boston, MA 02115 USA. RP Fox, CS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Heart, Lung, and Blood Institute [K12 HL083786] FX Division of Endocrinology, Metabolism and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts. This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195). Dr. Britton was supported by a Research Career Development Award (K12 HL083786) from the National Heart, Lung, and Blood Institute. All other authors have reported that they have no relationships relevant to the content of this paper to disclose. NR 17 TC 102 Z9 108 U1 5 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 3 PY 2013 VL 62 IS 10 BP 921 EP 925 DI 10.1016/j.jacc.2013.06.027 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 211IO UT WOS:000323900300012 PM 23850922 ER PT J AU Hu, J Ho, AL Yuan, L Hu, BL Hua, SJ Hwang, SS Zhang, JH Hu, TY Zheng, HW Gan, BY Wu, GX Wang, YA Chin, LD DePinho, RA AF Hu, Jian Ho, Allen L. Yuan, Liang Hu, Baoli Hua, Sujun Hwang, Soyoon Sarah Zhang, Jianhua Hu, Tianyi Zheng, Hongwu Gan, Boyi Wu, Gongxiong Wang, Yaoqi Alan Chin, Lynda DePinho, Ronald A. TI Neutralization of terminal differentiation in gliomagenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE oncogenomics; cancer stem cells ID EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-INITIATING CELLS; STEM-CELLS; HUMAN GLIOBLASTOMA; HUMAN FIBROBLASTS; 13-CIS-RETINOIC ACID; FUNCTIONAL-NEURONS; DIRECT CONVERSION; RAS; TROPOMYOSIN AB An immature state of cellular differentiation-characterized by stem cell-like tendencies and impaired differentiation-is a hallmark of cancer. Using glioblastoma multiforme (GBM) as a model system, we sought to determine whether molecular determinants that drive cells toward terminal differentiation are also genetically targeted in carcinogenesis and whether neutralizing such genes also plays an active role to reinforce the impaired differentiation state and promote malignancy. To that end, we screened 71 genes with known roles in promoting nervous system development that also sustain copy number loss in GBM through antineoplastic assay and identified A2BP1 (ataxin 2 binding protein 1, Rbfox1), an RNA-binding and splicing regulator that is deleted in 10% of GBM cases. Integrated in silico analysis of GBM profiles to elucidate the A2BP1 pathway and its role in glioma identified myelin transcription factor 1-like (Myt1L) as a direct transcriptional regulator of A2BP1. Reintroduction of A2BP1 or Myt1L in GBM cell lines and glioma stem cells profoundly inhibited tumorigenesis in multiple assays, and conversely, shRNA-mediated knockdown of A2BP1 or Myt1L in premalignant neural stem cells compromised neuronal lineage differentiation and promoted orthotopic tumor formation. On the mechanistic level, with the top-represented downstream target TPM1 as an illustrative example, we demonstrated that, among its multiple functions, A2BP1 serves to regulate TPM1's alternative splicing to promote cytoskeletal organization and terminal differentiation and suppress malignancy. Thus, in addition to the activation of self-renewal pathways, the neutralization of genetic programs that drive cells toward terminal differentiation may also promote immature and highly plastic developmental states that contribute to the aggressive malignant properties of GBM. C1 [Hu, Jian; Ho, Allen L.; Yuan, Liang; Hu, Baoli; Hua, Sujun; Hwang, Soyoon Sarah; Wang, Yaoqi Alan; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Hu, Jian; Ho, Allen L.; Yuan, Liang; Hu, Baoli; Hua, Sujun; Hwang, Soyoon Sarah; Zhang, Jianhua; Wang, Yaoqi Alan; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Gan, Boyi] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Zhang, Jianhua] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. [Ho, Allen L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hu, Tianyi] Duke Univ, Trinity Coll Arts & Sci, Durham, NC 27708 USA. [Zheng, Hongwu] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Wu, Gongxiong] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. EM rdepinho@mdanderson.org OI Zheng, Hongwu/0000-0002-5823-4913 FU National Institutes of Health (NIH) [K99/R00, 5K99CA172700]; Leukemia and Lymphoma Society; Department of Defense [TS093049]; Prostate Cancer Research Program (PCRP) Exploration-Hypothesis Development Grant [PC100356]; Helen Hay Whitney Foundation; Juvenile Diabetes Research Foundation [10-2012-240]; NIH [P01 5P01CA095616, U01 5U01CA084313] FX We thank S. Jiang, R. Narurkar, and E. Fletcher-Sananikone for excellent mouse husbandry and care and all members of the DePinho and Chin laboratories for helpful discussion. We also thank H. Zhang and Y. Xiao for the bioinformatic analysis. J.H. is supported by National Institutes of Health (NIH) K99/R00 Pathway to Independence Award 5K99CA172700. J.H. and B.G. were supported by a Leukemia and Lymphoma Society fellowship. B.G. is supported by the Department of Defense Tuberous Sclerosis Complex Research Program (TSCRP) Career Transition Grant TS093049 and Prostate Cancer Research Program (PCRP) Exploration-Hypothesis Development Grant PC100356. H.Z. was supported by the Helen Hay Whitney Foundation. G.W. is supported by Juvenile Diabetes Research Foundation Grant 10-2012-240. L.C. and R.A.D. are supported by NIH Grants P01 5P01CA095616 and U01 5U01CA084313. R.A.D. is an Ellison Foundation for Medical Research Senior Scholar and an American Cancer Society Research Professor. NR 50 TC 24 Z9 24 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 2013 VL 110 IS 36 BP 14520 EP 14527 DI 10.1073/pnas.1308610110 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 211DY UT WOS:000323886200021 PM 23918370 ER PT J AU Tompkins, RG Warren, HS Mindrinos, MN Xiao, WZ Davis, RW AF Tompkins, Ronald G. Warren, H. Shaw Mindrinos, Michael N. Xiao, Wenzhong Davis, Ronald W. TI Reply to Osterburg et al.: To study human inflammatory diseases in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 [Tompkins, Ronald G.; Warren, H. Shaw; Xiao, Wenzhong; Davis, Ronald W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Tompkins, Ronald G.; Warren, H. Shaw; Xiao, Wenzhong; Davis, Ronald W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Tompkins, Ronald G.; Warren, H. Shaw; Xiao, Wenzhong; Davis, Ronald W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Mindrinos, Michael N.; Xiao, Wenzhong] Stanford Univ, Stanford Genome Technol Ctr, Stanford, CA 94305 USA. RP Davis, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. EM dbowe@stanford.edu FU NIGMS NIH HHS [U54 GM062119, R01 GM040586, R24 GM102656] NR 4 TC 4 Z9 4 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 2013 VL 110 IS 36 BP E3371 EP E3371 DI 10.1073/pnas.1307452110 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 211DY UT WOS:000323886200004 PM 24137798 ER PT J AU Franchetti, Y Anderson, SJ Sampson, AR AF Franchetti, Yoko Anderson, Stewart J. Sampson, Allan R. TI An Adaptive Two-Stage Dose-Response Design Method for Establishing Proof of Concept SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Adding and; or dropping treatment arms; Drug development; Proof of concept; Two-stage adaptive design; xMCP-Mod ID COMBINING MULTIPLE COMPARISONS; PHRMA WORKING GROUP; INTERIM; TRIALS; HYPOTHESES AB We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish global PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs. C1 [Franchetti, Yoko] Dana Faber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Franchetti, Yoko] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Anderson, Stewart J.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sampson, Allan R.] Univ Pittsburgh, Sch Arts & Sci, Dept Stat, Pittsburgh, PA USA. RP Franchetti, Y (reprint author), Dana Faber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM yoko.tnk@gmail.com OI Anderson, Stewart/0000-0001-8948-0650 FU NIMH [ACISR: P30 MH090333]; NIH/NCI [U10CA6965i] FX Stewart J. Anderson was partially supported by an NIMH grant, ACISR: P30 MH090333, and NIH/NCI grant U10CA6965i. The authors thank the associate editor and two referees for their helpful comments and suggestions. NR 24 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD SEP 3 PY 2013 VL 23 IS 5 BP 1124 EP 1154 DI 10.1080/10543406.2013.813519 PG 31 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 204ZJ UT WOS:000323409500013 PM 23957520 ER PT J AU Adland, E Carlson, JM Paioni, P Kloverpris, H Shapiro, R Ogwu, A Riddell, L Luzzi, G Chen, FB Balachandran, T Heckerman, D Stryhn, A Edwards, A Ndung'u, T Walker, BD Buus, S Goulder, P Matthews, PC AF Adland, Emily Carlson, Jonathan M. Paioni, Paolo Kloverpris, Henrik Shapiro, Roger Ogwu, Anthony Riddell, Lynn Luzzi, Graz Chen, Fabian Balachandran, Thambiah Heckerman, David Stryhn, Anette Edwards, Anne Ndung'u, Thumbi Walker, Bruce D. Buus, Soren Goulder, Philip Matthews, Philippa C. TI Nef-Specific CD8+T Cell Responses Contribute to HIV-1 Immune Control SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-I ALLELES; T-LYMPHOCYTE RESPONSES; ELITE CONTROLLERS; HLA-B; DISEASE PROGRESSION; SET-POINT; INFECTION; ESCAPE; GAG AB Recent studies in the SIV-macaque model of HIV infection suggest that Nef-specific CD8+ T-cell responses may mediate highly effective immune control of viraemia. In HIV infection Nef recognition dominates in acute infection, but in large cohort studies of chronically infected subjects, breadth of T cell responses to Nef has not been correlated with significant viraemic control. Improved disease outcomes have instead been associated with targeting Gag and, in some cases, Pol. However analyses of the breadth of Nef-specific T cell responses have been confounded by the extreme immunogenicity and multiple epitope overlap within the central regions of Nef, making discrimination of distinct responses impossible via IFN-gamma ELISPOT assays. Thus an alternative approach to assess Nef as an immune target is needed. Here, we show in a cohort of >700 individuals with chronic C-clade infection that >50% of HLA-B-selected polymorphisms within Nef are associated with a predicted fitness cost to the virus, and that HLA-B alleles that successfully drive selection within Nef are those linked with lower viral loads. Furthermore, the specific CD8+ T cell epitopes that are restricted by protective HLA Class I alleles correspond substantially to effective SIV-specific epitopes in Nef. Distinguishing such individual HIV-specific responses within Nef requires specific peptide-MHC I tetramers. Overall, these data suggest that CD8+ T cell targeting of certain specific Nef epitopes contributes to HIV suppression. These data suggest that a re-evaluation of the potential use of Nef in HIV T-cell vaccine candidates would be justified. C1 [Adland, Emily; Paioni, Paolo; Kloverpris, Henrik; Goulder, Philip] Univ Oxford, Dept Paediat, Oxford, England. [Carlson, Jonathan M.; Heckerman, David] Microsoft Res, eSci Grp, Los Angeles, CA USA. [Shapiro, Roger] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Shapiro, Roger; Ogwu, Anthony] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Riddell, Lynn] Northampton Gen Hosp, Northamptonshire Healthcare NHS Trust, Dept Genitourinary Med, Northampton, England. [Luzzi, Graz] Wycombe Gen Hosp, Dept Genitourinary Med, High Wycombe, Bucks, England. [Chen, Fabian] Royal Berkshire Hosp, Dept Sexual Hlth, Reading RG1 5AN, Berks, England. [Balachandran, Thambiah] Luton & Dunstable Hosp, Dept Genitourinary Med, Luton, Beds, England. [Kloverpris, Henrik; Stryhn, Anette; Buus, Soren] Univ Copenhagen, Fac Hlth Sci, Expt Immunol Lab, Copenhagen, Denmark. [Edwards, Anne] Churchill Hosp, Oxford Dept Genitourinary Med, Oxford OX3 7LJ, England. [Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. [Kloverpris, Henrik] Univ KwaZulu Natal, Nelson R Mandela Sch Med, K RITH, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Ndung'u, Thumbi; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Matthews, Philippa C.] Univ Oxford, Nuffield Dept Med, Oxford, England. RP Adland, E (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg Pathogen Res, Oxford, England. EM emily.adland@paediatrics.ox.ac.uk RI Buus, Soren/F-5446-2010; OI Matthews, Philippa/0000-0002-4036-4269; Ndung'u, Thumbi/0000-0003-2962-3992 FU Oxford University; Wellcome Trust; National Institutes of Health [R01 AI46995] FX PCM is funded by Oxford University as an National Institute for Health Research Clinical Lecturer. PG is supported by grants from the Wellcome Trust (Senior Clinical Fellowship) and by the National Institutes of Health, grant R01 AI46995. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 17 Z9 17 U1 0 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 2 PY 2013 VL 8 IS 9 AR UNSP e73117 DI 10.1371/journal.pone.0073117 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215VH UT WOS:000324238400045 PM 24023819 ER PT J AU Gouni-Berthold, I Berthold, HK Huh, JY Berman, R Spenrath, N Krone, W Mantzoros, CS AF Gouni-Berthold, Ioanna Berthold, Heiner K. Huh, Joo Young Berman, Reena Spenrath, Nadine Krone, Wilhelm Mantzoros, Christos S. TI Effects of Lipid-Lowering Drugs on Irisin in Human Subjects In Vivo and in Human Skeletal Muscle Cells Ex Vivo SO PLOS ONE LA English DT Article ID EZETIMIBE AND/OR SIMVASTATIN; CIRCULATING ADIPONECTIN; RANDOMIZED-TRIAL; HEALTHY-MEN; ENERGY-EXPENDITURE; INSULIN-RESISTANCE; LDL-CHOLESTEROL; STATIN THERAPY; MESSENGER-RNA; LEPTIN LEVELS AB Context and Objective: The myokine irisin has been proposed to regulate energy homeostasis. Little is known about its association with metabolic parameters and especially with parameters influencing pathways of lipid metabolism. In the context of a clinical trial, an exploratory post hoc analysis has been performed in healthy subjects to determine whether simvastatin and/or ezetimibe influence serum irisin levels. The direct effects of simvastatin on irisin were also examined in primary human skeletal muscle cells (HSKMCs). Design and Participants: A randomized, parallel 3-group study was performed in 72 men with mild hypercholesterolemia and without apparent cardiovascular disease. Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination. Results: Baseline irisin concentrations were not significantly correlated with age, BMI, estimated GFR, thyroid parameters, glucose, insulin, lipoproteins, non-cholesterol sterols, adipokines, inflammation markers and various molecular markers of cholesterol metabolism. Circulating irisin increased significantly in simvastatin-treated but not in ezetimibe-treated subjects. The changes were independent of changes in LDL-cholesterol and were not correlated with changes in creatine kinase levels. In HSKMCs, simvastatin significantly increased irisin secretion as well as mRNA expression of its parent peptide hormone FNDC5. Simvastatin significantly induced cellular reactive oxygen species levels along with expression of pro-and anti-oxidative genes such as Nox2, and MnSOD and catalase, respectively. Markers of cellular stress such as atrogin-1 mRNA and Bax protein expression were also induced by simvastatin. Decreased cell viability and increased irisin secretion by simvastatin was reversed by antioxidant mito-TEMPO, implying in part that irisin is secreted as a result of increased mitochondrial oxidative stress and subsequent myocyte damage. Conclusions: Simvastatin increases irisin concentrations in vivo and in vitro. It remains to be determined whether this increase is a result of muscle damage or a protective mechanism against simvastatin-induced cellular stress. Trial Registration: ClinicalTrials.gov NCT00317993 http://clinicaltrials.gov/ct2/show/NCT00317993. C1 [Gouni-Berthold, Ioanna; Spenrath, Nadine; Krone, Wilhelm] Univ Cologne, Ctr Endocrinol Diabet & Prevent Med, D-50931 Cologne, Germany. [Berthold, Heiner K.] Charite, EGZB, D-13353 Berlin, Germany. [Berthold, Heiner K.] Interdisciplinary Metab Ctr, Lipid Clin, Virchow Clin Campus, Berlin, Germany. [Huh, Joo Young; Berman, Reena; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Huh, Joo Young; Berman, Reena; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Gouni-Berthold, I (reprint author), Univ Cologne, Ctr Endocrinol Diabet & Prevent Med, D-50931 Cologne, Germany. EM ioanna.berthold@uni-koeln.de FU MSD Sharp & Dohme (Munich, Germany); Wilhelm-Doerenkamp Foundation (Cologne, Germany) FX The parent trial (1) was supported in part by an investigator-initiated grant from MSD Sharp & Dohme (Munich, Germany) and the Wilhelm-Doerenkamp Foundation (Cologne, Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 39 Z9 40 U1 3 U2 24 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 2 PY 2013 VL 8 IS 9 AR e72858 DI 10.1371/journal.pone.0072858 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 215VH UT WOS:000324238400030 PM 24023786 ER PT J AU Singh, R Gorstein, SV Bednarek, F Chou, JH McGowan, EC Visintainer, PF AF Singh, Rachana Gorstein, Samuel V. Bednarek, Frank Chou, Joseph H. McGowan, Elisabeth C. Visintainer, Paul F. TI A Predictive Model for SIVH risk in Preterm Infants and Targeted Indomethacin Therapy for Prevention SO SCIENTIFIC REPORTS LA English DT Article ID LOW-BIRTH-WEIGHT; NEONATAL INTENSIVE-CARE; INTRAVENTRICULAR HEMORRHAGE; HEAD ULTRASOUND; TRIAL; PROPHYLAXIS; OUTCOMES; AGE; SEVERITY; DELIVERY AB Prophylactic indomethacin may decrease Severe Intraventricular Hemorrhage (SIVH). Our goal was to develop a predictive model for SIVH using parameters available by six hours of age. De-identified data for preterm infants born <= 34 weeks gestational age was abstracted from Vermont Oxford Network database. Using clinical variables available by 6 hrs of age the model was developed, and validated. Statistical methods were used to evaluate the ability of the model to discriminate infants with and without SIVH and, to compare observed and predicted risk. The model achieved excellent discrimination as indicated by ROC curve of 0.85. A good agreement was noted between observed and predicted risk (HLtest: p = 0.22). Application of the model to patients receiving indomethacin suggests a benefit at the highest risk levels. We have developed a valid predictive model for predicting SIVH as well as shown that exposure to indomethacin decreases the incidence of SIVH overall. C1 [Singh, Rachana; Gorstein, Samuel V.] Baystate Childrens Hosp, Springfield, MA USA. [Singh, Rachana; McGowan, Elisabeth C.; Visintainer, Paul F.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Gorstein, Samuel V.; Chou, Joseph H.] Mass Gen Hosp, Boston, MA USA. [Bednarek, Frank] UMass Mem Med Ctr, Worcester, MA USA. [McGowan, Elisabeth C.] Tufts Med Ctr, Boston, MA USA. [Visintainer, Paul F.] Baystate Med Ctr, Springfield, MA USA. RP Singh, R (reprint author), Baystate Childrens Hosp, Springfield, MA USA. EM Rachana.singhmd@bhs.org NR 29 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD SEP 2 PY 2013 VL 3 AR 2539 DI 10.1038/srep02539 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209CW UT WOS:000323732800001 PM 23995978 ER PT J AU Levey, EJ Borba, CPC Harris, BL Carney, JR Dominguez, S Wang, EKS Boxill, R Henderson, DC AF Levey, E. J. Borba, C. P. C. Harris, B. L. Carney, J. R. Dominguez, S. Wang, E. K. S. Boxill, R. Henderson, D. C. TI Assessment of the needs of vulnerable youth populations in post-conflict Liberia SO AFRICAN JOURNAL OF PSYCHIATRY LA English DT Article DE Post-Conflict Liberia; Mental Health Needs Assessment; Children and Adolescents ID AFFECTED CHILDREN; HEALTH; IMPACT AB Objective: The study examined key informants' perceptions of the emotional impact of traumatic events, major problems, functional limitations and appropriate treatment settings for children, adolescents, and young adults in post-conflict Liberia. Method: This research is a based on cross-sectional survey conducted between March 30, 2009 and April 30, 2009 in Liberia with 171 local key Liberian informants. Analysis was conducted using mixed methods. The findings we will report were collected in the qualitative portion of the survey. Results: We found that while different interventions were preferred for different types of young people, some interventions were mentioned for all youth and by all age and gender groups of key informants. These included counseling, education, and skills training. Also frequently chosen were housing, community reintegration, recreation, and medical care. In general, key informants reported similar concerns regardless of their ages or genders. Notable exceptions to this were in interventions for youth who joined fighting forces. Men over 50 were the only ones to recommend apology and reparations. Similarly, in recommendations for criminals and violent youth, a number of men mentioned prison, whereas the women did not. Conclusion: Our findings suggest that the needs of post-conflict Liberian youth span a variety of domains, including physical, emotional, medical, psychological, and educational. These findings can be used to guide the development of treatment programs for these young people. C1 [Levey, E. J.; Borba, C. P. C.; Carney, J. R.; Dominguez, S.; Wang, E. K. S.; Boxill, R.; Henderson, D. C.] Massachusetts Gen Hosp, MD Div Global Psychiat, Boston, MA 02114 USA. [Borba, C. P. C.; Wang, E. K. S.; Henderson, D. C.] Harvard Univ, Sch Med, Boston, MA USA. [Harris, B. L.] Univ Liberia, AM Dogliotti Coll Med, Monrovia, Liberia. RP Levey, EJ (reprint author), Massachusetts Gen Hosp, MD Div Global Psychiat, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM elevey@partners.org NR 12 TC 3 Z9 3 U1 2 U2 9 PU IN HOUSE PUBLICATIONS PI JOHANNESBURG PA PO BOX 412748, CRAIGHALL 2024, JOHANNESBURG, 00000, SOUTH AFRICA SN 1994-8220 J9 AFR J PSYCHIATRY JI Afr. J. Psychiatry PD SEP PY 2013 VL 16 IS 5 BP 349 EP 355 DI 10.4314/ajpsy.v16i5.47 PG 7 WC Psychiatry SC Psychiatry GA AM2DL UT WOS:000339659200009 PM 24051668 ER PT J AU Feke, GT Rhee, DJ Turalba, AV Pasquale, LR AF Feke, Gilbert T. Rhee, Douglas J. Turalba, Angela V. Pasquale, Louis R. TI Effects of Dorzolamide-Timolol and Brimonidine-Timolol on Retinal Vascular Autoregulation and Ocular Perfusion Pressure in Primary Open Angle Glaucoma SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID NORMAL-TENSION GLAUCOMA; OPTIC DISC HEMORRHAGES; BLOOD-FLOW; INTRAOCULAR-PRESSURE; TARTRATE 0.2-PERCENT; CARBONIC-ANHYDRASE; HEALTHY-SUBJECTS; VISUAL FUNCTION; RISK-FACTORS; PROGRESSION AB Purpose: To assess whether dorzolamide 2%-timolol 0.5% (D/T) and/or brimonidine 0.2%-timolol 0.5% (B/T) alters retinal vascular autoregulation (RVA) and seated ocular perfusion pressure (sOPP) in primary open angle glaucoma (POAG) patients who demonstrate retinal vascular dysregulation (RVD) on timolol 0.5% alone. Methods: In this prospective, observer-masked, crossover study, 21 POAG patients with untreated intraocular pressure (IOP) >21 mm Hg were treated for 6 weeks with timolol 0.5%. Subsequently, we measured inferior temporal retinal artery blood flow in the left eye with subjects seated and then while reclined for 30 min using the Canon Laser Blood Flowmeter. Subjects with a change in retinal blood flow in response to posture change outside of the range previously found in healthy subjects were designated as having RVD and randomized to either D/T or B/T for 6 weeks and re-tested. This was followed by treatment with the opposite medication. Results: Seven of the 21 subjects demonstrated RVD in response to posture change following timolol 0.5%. Multiple linear regression analysis indicated that lower sOPP was the main determinant of RVD (P = 0.033). After treatment with D/T, all 7 converted from RVD to normal RVA status (P = 0.001). Four of 6 subjects showed a similar return to normal RVA following B/T (P = 0.066). Mid-morning sOPP was 41.1 +/- 5.5 mm Hg post-timolol, 46.3 +/- 6.5mmHg post-D/T, and 38.6 +/- 6.0 mmHg post-B/T (D/T vs. B/T, P = 0.026). Conclusions: D/T significantly improved RVA in POAG patients exhibiting RVD while on timolol 0.5% alone. D/T also increased sOPP compared to B/T. There was no significant difference (P = 0.37) between D/T and B/T in improving RVA. C1 [Feke, Gilbert T.; Rhee, Douglas J.; Turalba, Angela V.; Pasquale, Louis R.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pasquale, LR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM louis_pasquale@meei.harvard.edu NR 48 TC 7 Z9 7 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1080-7683 EI 1557-7732 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD SEP PY 2013 VL 29 IS 7 BP 639 EP 645 DI 10.1089/jop.2012.0271 PG 7 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA AL6UO UT WOS:000339268700006 PM 23530946 ER PT J AU Walensky, RP AF Walensky, Rochelle P. TI Combination HIV Prevention: The Value and Interpretation of Mathematical Models SO CURRENT HIV/AIDS REPORTS LA English DT Editorial Material DE Combination HIV prevention; Test and treat; Mathematical models; HIV; Cost-effectiveness; HIV transmission ID CONTROLLED-TRIALS AB Mathematical models of HIV prevention interventions often provide critical insights related to programmatic design and economic efficiency. One recent dynamic model by Long et al. highlights that a combination prevention approach - with testing, treatment, circumcision, microbicides and PrEP - may decrease transmissions by over 60 % and may be very cost-effective in South Africa. In this analysis, the authors introduce the critical concept of joint effectiveness of preventions programs and demonstrate how some programs operate synergistically (HIV screening coupled with early treatment) while others may create redundancies (microbicides coupled with pre-exposure prophylaxis). Whether combination HIV prevention programs perform with additive, multiplicative or maximal effectiveness will be important to consider in anticipation of their combined transmission impact. C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [R01 AI093269] NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD SEP PY 2013 VL 10 IS 3 BP 195 EP 198 DI 10.1007/s11904-013-0167-7 PG 4 WC Infectious Diseases SC Infectious Diseases GA AJ7TP UT WOS:000337900600001 PM 23797377 ER PT J AU Triant, VA AF Triant, Virginia A. TI Cardiovascular Disease and HIV Infection SO CURRENT HIV/AIDS REPORTS LA English DT Article DE HIV; Cardiovascular; Coronary; Myocardial infarction; Risk factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; POPULATION-BASED COHORT; RECEIVING ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; CAROTID-ARTERY-DISEASE; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; HEALTH-CARE-SYSTEM AB The emergence of chronic disease complications in controlled HIV disease has changed the landscape of HIV clinical care. HIV infection confers an increased cardiovascular disease risk, which is thought to be due to a complex interplay of mechanistic factors. While traditional cardiovascular risk factors likely play a role, recent evidence suggests that HIV-associated inflammation and immune activation are important mediators of cardiovascular risk. It is unclear whether established preventative interventions for the general population are applicable to HIV-infected patients, and the need to translate mechanistic knowledge into HIV-specific clinical interventions represents an important priority. Developing strategies to prevent cardiovascular disease in HIV-infected individuals calls for a multidisciplinary approach and represents an opportunity to exert a major public health impact in an at-risk population. C1 [Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Triant, Virginia A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Triant, Virginia A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Triant, VA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM vtriant@partners.org FU NIAID NIH HHS [K01 AI073109] NR 100 TC 9 Z9 9 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD SEP PY 2013 VL 10 IS 3 BP 199 EP 206 DI 10.1007/s11904-013-0168-6 PG 8 WC Infectious Diseases SC Infectious Diseases GA AJ7TP UT WOS:000337900600002 PM 23793823 ER PT J AU Shin, J Liang, SY Hassett, MJ Phillips, KA Haas, JS AF Shin, Jaekyu Liang, Su-Ying Hassett, Michael J. Phillips, Kathryn A. Haas, Jennifer S. TI Utilization of cardiac monitoring tests in women with nonmetastatic breast cancer treated with trastuzumab SO PERSONALIZED MEDICINE LA English DT Article DE breast cancer; cardiac monitoring; personalized medicine; quality-of-care; trastuzumab ID ADJUVANT CHEMOTHERAPY; MANAGEMENT; RECOMMENDATIONS; THERAPY; PLUS AB Aims: Trastuzumab, one of the best known examples of personalized medicine, requires regular cardiac monitoring because it can cause heart failure. We aimed to assess the utilization of cardiac monitoring in women with nonmetastatic breast cancer receiving trastuzumab-based chemotherapy in routine clinical practice. Patients & methods: The medical records of women continuously enrolled in a large national health insurance plan who were diagnosed with nonmetastatic breast cancer and treated with trastuzumab from 2006 to 2008 were reviewed (n = 109). The primary outcome variables were the use and type of cardiac monitoring testing before and during trastuzumab therapy. An exploratory multivariable logistic regression ana-lysis was performed to identify predictors for receiving cardiac monitoring both at baseline and during trastuzumab treatment. Results: Monitoring both before and during therapy was less common (62%), although 74% had cardiac monitoring before therapy and 80% had at least one test during therapy. Radionuclide ventriculogram was utilized more often than echocardiography (48 vs 42%). Only the use of anthracycline (odds ratio: 2.39; 95% CI: 1.01-5.71) was significantly associated with use of a cardiac monitoring both at baseline and during trastuzumab treatment. Conclusion: The use of cardiac monitoring testing was variable and opportunities to improve quality and reduce cost are evident. These results have clinical implications for other personalized medicine interventions requiring regular laboratory monitoring. C1 [Shin, Jaekyu; Liang, Su-Ying; Phillips, Kathryn A.] Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, San Francisco, CA 94143 USA. [Shin, Jaekyu; Liang, Su-Ying; Phillips, Kathryn A.] UCSF Ctr Translat & Policy Res Personalized Med T, San Francisco, CA 94143 USA. [Hassett, Michael J.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Shin, J (reprint author), Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, 521 Parnassus St,C-152,Box 0622, San Francisco, CA 94143 USA. EM shinj@pharmacy.ucsf.edu FU National Cancer Institute [P01 CA130818]; NIH/NCRR UCSF-CTSI [UL1 RR024131] FX This project was supported by the National Cancer Institute through P01 CA130818 and, in part, by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. 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 16 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PD SEP PY 2013 VL 10 IS 7 BP 703 EP 708 DI 10.2217/PME.13.68 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI8PX UT WOS:000337184100011 ER PT J AU van der Wilden, GM Janjua, S Wedel, SK Agarwal, S Shapiro, ML Andersen, ND Odom, SR Gates, JD Frakes, MA Chang, YC Velmahos, GC Alam, HB King, DR De Moya, MA AF van der Wilden, Gwendolyn M. Janjua, Sumbal Wedel, Suzanne K. Agarwal, Suresh Shapiro, Mark L. Andersen, Nicholas D. Odom, Stephen R. Gates, Jonathan D. Frakes, Michael A. Chang, Yuchiao Velmahos, George C. Alam, Hasan B. King, David R. De Moya, Marc A. TI Multi-institutional Comparison of Helicopter Transfers Directly to the Operating Room versus the Pit Stop in the Emergency Department SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the New-England-Surgical-Society CY SEP 23-25, 2011 CL Bretton Woods, NH SP New England Surg Soc ID DEMONSTRATE IMPROVED OUTCOMES; TRAUMA PATIENTS; TRANSPORT; INJURY; SYSTEM; SCENE; MORTALITY C1 [van der Wilden, Gwendolyn M.; Janjua, Sumbal; Chang, Yuchiao; Velmahos, George C.; Alam, Hasan B.; King, David R.; De Moya, Marc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [van der Wilden, Gwendolyn M.; Janjua, Sumbal; Odom, Stephen R.; Gates, Jonathan D.; Chang, Yuchiao; Velmahos, George C.; Alam, Hasan B.; King, David R.; De Moya, Marc A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wedel, Suzanne K.; Frakes, Michael A.] Boston MedFlight, Boston, MA USA. [Agarwal, Suresh] Boston Med Ctr, Boston, MA USA. [Agarwal, Suresh] Boston Univ, Boston, MA 02215 USA. [Shapiro, Mark L.; Andersen, Nicholas D.] Duke Univ, Med Ctr, Durham, NC USA. [Shapiro, Mark L.; Andersen, Nicholas D.] Duke Univ, Durham, NC USA. [Odom, Stephen R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Gates, Jonathan D.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP van der Wilden, GM (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvanderwilden@gmail.com NR 15 TC 0 Z9 0 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD SEP PY 2013 VL 79 IS 9 BP 939 EP 943 PG 5 WC Surgery SC Surgery GA AI6EN UT WOS:000336963800034 PM 24069995 ER PT J AU Patel, MS Elias, N Hertl, M Vagefi, PA AF Patel, Madhukar S. Elias, Nahel Hertl, Martin Vagefi, Parsia A. TI Elevated Creatinine after Kidney Transplantation SO AMERICAN SURGEON LA English DT Article ID TRANSCATHETER EMBOLIZATION; BIOPSY; IMMEDIATE C1 [Patel, Madhukar S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Surg, Boston, MA USA. [Elias, Nahel; Hertl, Martin; Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat Surg, Boston, MA USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 544b, Boston, MA 02114 USA. EM pvagefi@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD SEP PY 2013 VL 79 IS 9 BP E308 EP E309 PG 2 WC Surgery SC Surgery GA AI6EN UT WOS:000336963800010 PM 24069971 ER PT J AU Beach, MC Roter, D Korthuis, PT Epstein, RM Sharp, V Ratanawongsa, N Cohn, J Eggly, S Sankar, A Moore, RD Saha, S AF Beach, Mary Catherine Roter, Debra Korthuis, P. Todd Epstein, Ronald M. Sharp, Victoria Ratanawongsa, Neda Cohn, Jonathon Eggly, Susan Sankar, Andrea Moore, Richard D. Saha, Somnath TI A Multicenter Study of Physician Mindfulness and Health Care Quality SO ANNALS OF FAMILY MEDICINE LA English DT Article DE patient-physician relations; patient-physician communication; mindfulness; HIV; acquired immunodeficiency syndrome ID PATIENT-PROVIDER COMMUNICATION; STRESS REDUCTION; CLINICAL-PRACTICE; MEDICAL-STUDENTS; HIV; SATISFACTION; PROGRAM; PARTICIPATION; CENTEREDNESS; ADHERENCE AB PURPOSE Mindfulness (ie, purposeful and nonjudgmental attentiveness to one's own experience, thoughts, and feelings) is associated with physician well-being. We sought to assess whether clinician self-rated mindfulness is associated with the quality of patient care. METHODS We conducted an observational study of 45 clinicians (34 physicians, 8 nurse practitioners, and 3 physician assistants) caring for patients infected with the human immunodeficiency virus (HIV) who completed the Mindful Attention Awareness Scale and 437 HIV-infected patients at 4 HIV specialty clinic sites across the United States. We measured patient-clinician communication quality with audio-recorded encounters coded using the Roter Interaction Analysis System (RIAS) and patient ratings of care. RESULTS In adjusted analyses comparing clinicians with highest and lowest tertile mindfulness scores, patient visits with high-mindfulness clinicians were more likely to be characterized by a patient-centered pattern of communication (adjusted odds ratio of a patient-centered visit was 4.14; 95% CI, 1.58-10.86), in which both patients and clinicians engaged in more rapport building and discussion of psychosocial issues. Clinicians with high-mindfulness scores also displayed more positive emotional tone with patients (adjusted beta = 1.17; 95% CI, 0.46-1.9). Patients were more likely to give high ratings on clinician communication (adjusted prevalence ratio [APR] = 1.48; 95% CI, 1.17-1.86) and to report high overall satisfaction (APR = 1.45; 95 CI, 1.15-1.84) with high-mindfulness clinicians. There was no association between clinician mindfulness and the amount of conversation about biomedical issues. CONCLUSIONS Clinicians rating themselves as more mindful engage in more patient-centered communication and have more satisfied patients. Interventions should determine whether improving clinician mindfulness can also improve patient health outcomes. C1 [Beach, Mary Catherine; Roter, Debra; Moore, Richard D.] Johns Hopkins Univ, Baltimore, MD USA. [Korthuis, P. Todd; Saha, Somnath] Oregon Hlth & Sci Univ, Portland, OR USA. [Epstein, Ronald M.] Univ Rochester, Rochester, NY USA. [Sharp, Victoria] St Lukes Roosevelt Hosp, New York, NY USA. [Ratanawongsa, Neda] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cohn, Jonathon; Eggly, Susan; Sankar, Andrea] Wayne State Univ, Detroit, MI USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. RP Beach, MC (reprint author), Johns Hopkins Univ, Div Gen Internal Med, Room 2-511,2024 East Monument St, Baltimore, MD 21287 USA. EM mcbeach@jhmi.edu RI Roter, Debra/N-8830-2014; OI Eggly, Susan/0000-0002-8137-6098 FU Health Resources Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; National Institute of Drug Abuse [K23 DA019809]; Department of Veterans Affairs; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). In addition, Dr Korthuis was supported by the National Institute of Drug Abuse (K23 DA019809), Dr Saha was supported by the Department of Veterans Affairs, Dr Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05), and both Drs Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. NR 39 TC 33 Z9 33 U1 4 U2 11 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD SEP-OCT PY 2013 VL 11 IS 5 BP 421 EP 428 DI 10.1370/afm.1507 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AI3XN UT WOS:000336799100006 PM 24019273 ER PT J AU Wanyenze, RK Kamya, MR Fatch, R Mayanja-Kizza, H Baveewo, S Szekeres, G Bangsberg, DR Coates, T Hahn, JA AF Wanyenze, Rhoda K. Kamya, Moses R. Fatch, Robin Mayanja-Kizza, Harriet Baveewo, Steven Szekeres, Gregory Bangsberg, David R. Coates, Thomas Hahn, Judith A. TI Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial SO LANCET GLOBAL HEALTH LA English DT Article ID SUB-SAHARAN AFRICA; ANTENATAL CARE; COUNTRIES; SETTINGS; EFFICACY; ACCESS; RISK AB Background HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its effect on HIV risk is uncertain and methods to improve linkage to care have not been studied. Methods We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data officer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6 . 5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). Findings We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27.9%] vs 251/890 [28.2%], diff erence -0.3%, one-sided 95% CI 3.2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0.61, 95% CI 0.44-0.83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a significant effect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per mu L or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0.60, 95% CI 0.41-0.87) and time to HIV care was decreased among women (0.80, 0.66-0.96). Interpretation Abbreviated HIV counselling and testing did not adversely affect risk behaviour. Linkage to care interventions might decrease time to enrolment in HIV care and antiretroviral treatment and thus might affect secondary HIV transmission and improve treatment outcomes. C1 [Wanyenze, Rhoda K.] Makerere Univ Sch Publ Hlth, Dept Dis Control & Environm Hlth, Kampala, Uganda. [Kamya, Moses R.; Mayanja-Kizza, Harriet; Baveewo, Steven] Makerere Univ Sch Med, Dept Med, Kampala, Uganda. [Fatch, Robin; Hahn, Judith A.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA. [Szekeres, Gregory; Coates, Thomas] Univ Calif Los Angeles David Geff Sch Med, Div Infect Dis, Los Angeles, CA USA. [Bangsberg, David R.] Massachusetts Gen Hosp Ctr Global Hlth, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. RP Wanyenze, RK (reprint author), Makerere Univ Sch Publ Hlth, POB 7072, Kampala, Uganda. EM rwanyenze@hotmail.com FU US National Institute of Mental Health [1 R01 MH077512] FX This study was funded by the US National Institute of Mental Health (1 R01 MH077512). We thank the members of the data safety monitoring board for providing oversight for this study. We acknowledge the support from the management of Mulago Hospital and thank the participants and study team for making this study possible. NR 34 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD SEP PY 2013 VL 1 IS 3 BP E137 EP E145 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH8XY UT WOS:000336422700015 PM 25104262 ER PT J AU Joynt, KE Orav, EJ Jha, AK AF Joynt, Karen E. Orav, E. John Jha, Ashish K. TI Physician Volume, Specialty, and Outcomes of Care for Patients With Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE health care costs; heart failure; patient readmission; quality of health care ID ACUTE MYOCARDIAL-INFARCTION; HOSPITAL VOLUME; MEDICARE BENEFICIARIES; MORTALITY-RATES; COSTS; ASSOCIATION; PNEUMONIA; QUALITY; SURGERY AB Background There is an urgent need to improve outcomes and reduce costs for patients with heart failure (HF). Physician volume is associated with better outcomes for patients undergoing procedures, but its association with outcomes for medically managed diseases, such as HF, is not well understood. Methods and Results We used Medicare inpatient data in 2009 to examine all HF admissions to acute care hospitals in the United States. We divided physicians into quintiles according to their volume of patients with HF. We used patient-level regression to compare 30-day risk-adjusted mortality, readmissions, and costs across volume groups, controlling for patient, physician, and hospital characteristics. We examined physician volume within strata of hospital volume and physician specialty. Patients cared for by the high-volume physicians had lower mortality than those by the low-volume physicians (8.9% versus 9.7%; P<0.001); this relationship was strongest in low-volume hospitals. In contrast, patients cared for by high-volume physicians had higher readmission rates (25.8% versus 21.5%; P<0001); this relationship was similar across hospital volume groups. Finally, costs were higher for the high-volume physicians ($8982 versus $8731; P=0.002, a difference that was consistent across hospital volume groups). The relationship between physician volume and mortality was strongest for internists (9.2% versus 10.6%; P<0.001) and weakest for cardiologists (6.4% versus 6.7%; P=0.485). Conclusions Physician volume is associated with lower mortality for HF, particularly in low-volume institutions and among noncardiologist physicians. Our findings suggest that clinician expertise may play an important role in HF care. C1 [Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Orav, E. John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Orav, E. John; Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Joynt, Karen E.; Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org FU American Heart Association [10CRP3780037]; Brigham and Women's Hospital, Cardiovascular Division FX Dr Joynt was supported by Clinical Research Program Grant 10CRP3780037 from the American Heart Association and the Lerner Research Award from Brigham and Women's Hospital, Cardiovascular Division. The other authors have no conflicts to report. NR 21 TC 12 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2013 VL 6 IS 5 BP 890 EP 897 DI 10.1161/CIRCHEARTFAILURE.112.000064 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG2GO UT WOS:000335234500006 PM 23926203 ER PT J AU Dadu, RT Dodge, R Nambi, V Virani, SS Hoogeveen, RC Smith, NL Chen, FJ Pankow, JS Guild, C Tang, WHW Boerwinkle, E Hazen, SL Ballantyne, CM AF Dadu, Razvan T. Dodge, Rhiannon Nambi, Vijay Virani, Salim S. Hoogeveen, Ron C. Smith, Nicholas L. Chen, Fengju Pankow, James S. Guild, Cameron Tang, W. H. Wilson Boerwinkle, Eric Hazen, Stanley L. Ballantyne, Christie M. TI Ceruloplasmin and Heart Failure in the Atherosclerosis Risk in Communities Study SO CIRCULATION-HEART FAILURE LA English DT Article DE cardiovascular diseases; ceruloplasmin; heart failure; polymorphism; single nucleotide ID SENSITIVE PLASMA-PROTEINS; ACUTE-PHASE PROTEINS; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; SERUM CERULOPLASMIN; CARDIOVASCULAR RISK; OXIDATIVE STRESS; NITRIC-OXIDE; DISEASE; ASSOCIATION AB Background Ceruloplasmin (Cp) decreases nitric oxide bioavailability in blood and has been associated with cardiovascular disease (CVD) in clinical studies. We assessed the associations between Cp and incident heart failure (HF), death, and CVD in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results Cp was measured at ARIC visit 4 (1996-1998). We studied 9240 individuals without HF or CVD at ARIC visit 4 and followed them for a mean of 10.5 years. Genome-wide association study was performed to identify genetic determinants of Cp levels and evaluate their association with incident HF in ARIC participants. Cp levels (meanSD) were higher in women versus men (335 +/- 79 versus 258 +/- 44 mg/L; P<0.0001), women on versus not on hormone-replacement therapy (398 +/- 89 versus 291 +/- 60 mg/L; P<0.0001), and African Americans versus whites (299 +/- 63 versus 293 +/- 74 mg/L; P=0.0005). After adjusting for traditional risk factors, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T, higher levels of Cp were associated with HF (hazard ratio, 1.44; 95% confidence interval, 1.13-1.83) and mortality (hazard ratio, 1.38; 95% confidence interval, 1.11-1.63). A locus on the ceruloplasmin gene on chromosome 3 was significantly associated with Cp levels (normal 295.56 +/- 77.60 mg/L; heterozygote 316.72 +/- 88.02 mg/L; homozygote 331.04 +/- 85.40 mg/L; P=8.3x10(-13)) but not with incident HF. After adjustment for traditional risk factors, Cp levels were also weekly associated with CVD. Conclusions Cp was associated with incident HF, mortality, and CVD in the ARIC population. A single locus on chromosome 3 was associated with Cp levels but not with HF. C1 [Dadu, Razvan T.; Nambi, Vijay; Virani, Salim S.; Hoogeveen, Ron C.; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Dadu, Razvan T.; Nambi, Vijay; Virani, Salim S.; Hoogeveen, Ron C.; Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Dodge, Rhiannon; Chen, Fengju; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Virani, Salim S.] Michael E DeBakey VA Med Ctr Hlth Serv, Res & Dev Ctr Excellence, Hlth Policy & Qual Program, Houston, TX USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Guild, Cameron] Univ Mississippi, Med Ctr, Div Cardiovasc Dis, Jackson, MS 39216 USA. [Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin Fdn, Cleveland, OH USA. [Smith, Nicholas L.] Univ Washington, Dept Cardiovasc Res, Seattle, WA 98195 USA. RP Ballantyne, CM (reprint author), Baylor Coll Med, 6565 Fannin St,MS A601, Houston, TX 77030 USA. EM cmb@bcm.edu OI Virani, Salim/0000-0001-9541-6954; Pankow, James/0000-0001-7076-483X FU National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820110 0009C, HHSN268201100010C, HHSN268201100011C, HHSN 268201100012C, R01HL087641, R01HL59367, R01HL 086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C]; NIH [UL1RR025005, 2P01HL076491, 1R01HL103931]; NIH Roadmap for Medical Research FX The Atherosclerosis Risk in Communities study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820110 0009C, HHSN268201100010C, HHSN268201100011C, and HHSN 268201100012C), R01HL087641, R01HL59367, and R01HL 086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health (NIH) contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This work was also supported by NIH grants 2P01HL076491 (Dr Hazen) and 1R01HL103931 (Dr Tang). NR 29 TC 12 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2013 VL 6 IS 5 BP 936 EP 943 DI 10.1161/CIRCHEARTFAILURE.113.000270 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG2GO UT WOS:000335234500012 PM 23861484 ER PT J AU Homma, S Thompson, JLP Sanford, AR Mann, DL Sacco, RL Levin, B Pullicino, PM Freudenberger, RS Teerlink, JR Graham, S Mohr, JP Massie, BM Labovitz, AJ Di Tullio, MR Gabriel, AP Lip, GYH Estol, CJ Lok, DJ Ponikowski, P Anker, SD AF Homma, Shunichi Thompson, John L. P. Sanford, Alexandra R. Mann, Douglas L. Sacco, Ralph L. Levin, Bruce Pullicino, Patrick M. Freudenberger, Ronald S. Teerlink, John R. Graham, Susan Mohr, J. P. Massie, Barry M. Labovitz, Arthur J. Di Tullio, Marco R. Gabriel, Andre P. Lip, Gregory Y. H. Estol, Conrado J. Lok, Dirk J. Ponikowski, Piotr Anker, Stefan D. CA WARCEF Investigators TI Benefit of Warfarin Compared With Aspirin in Patients With Heart Failure in Sinus Rhythm A Subgroup Analysis of WARCEF, a Randomized Controlled Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE aspirin; heart failure; sinus rhythm; stroke; warfarin ID ATRIAL-FIBRILLATION; SURVIVAL; THERAPY; DISEASE; STROKE AB Background The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin. Methods and Results We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03). Conclusions In patients <60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients 60 years, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. C1 [Homma, Shunichi; Di Tullio, Marco R.; Gabriel, Andre P.] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10032 USA. [Mohr, J. P.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Thompson, John L. P.; Sanford, Alexandra R.; Levin, Bruce] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Mann, Douglas L.] Washington Univ, Dept Med, St Louis, MO USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. [Pullicino, Patrick M.] Univ Kent, Kent Inst Med & Hlth Sci, Canterbury, Kent, England. [Freudenberger, Ronald S.] Lehigh Valley Hosp, Dept Med, Div Cardiol, Allentown, PA USA. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, Cardiol Sect, San Francisco, CA USA. [Graham, Susan] SUNY Upstate Med Univ, Dept Med, Div Cardiol, Buffalo, NY USA. [Labovitz, Arthur J.] Univ S Florida, Dept Cardiovasc Med, Tampa, FL USA. [Lip, Gregory Y. H.] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Estol, Conrado J.] Ctr Neurol Tratamiento & Rehabil, Buenos Aires, DF, Argentina. [Lok, Dirk J.] Deventer Hosp, Dept Cardiol, Deventer, Netherlands. [Ponikowski, Piotr] Wroclaw Med Univ, Mil Hosp, Dept Heart Dis, Wroclaw, Poland. [Anker, Stefan D.] Charite, Campus Virchow Klinikum, Dept Cardiol, D-13353 Berlin, Germany. RP Homma, S (reprint author), Columbia Univ, Med Ctr, PH 3-342,622 W 168th St, New York, NY 10032 USA. EM sh23@columbia.edu RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Mann, Douglas /0000-0002-2516-0145 FU National Institute of Neurological Diseases and Stroke [U01-NS-043975, U01-NS-039143] FX The WARCEF trial was supported by grant nos. U01-NS-043975 to Dr Homma and U01-NS-039143 to Dr Thompson from the National Institute of Neurological Diseases and Stroke. Warfarin and warfarin placebo were provided by Taro Pharmaceuticals USA, and aspirin and aspirin placebo by Bayer HealthCare. NR 21 TC 13 Z9 15 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2013 VL 6 IS 5 BP 988 EP 997 DI 10.1161/CIRCHEARTFAILURE.113.000372 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AG2GO UT WOS:000335234500018 PM 23881846 ER PT J AU Anbil, S Rizvi, I Celli, JP Alagic, N Pogue, BW Hasan, T AF Anbil, Sriram Rizvi, Imran Celli, Jonathan P. Alagic, Nermina Pogue, Brian W. Hasan, Tayyaba TI Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE quantitative image analysis; functional imaging; metric validation; photodynamic therapy dose parameters; treatment response heterogeneity; treatment durability ID DERIVATIVE MONOACID RING; MULTICELL TUMOR SPHEROIDS; ENGINEERED MOUSE MODELS; CELL-DEATH PATHWAYS; IN-VITRO; DRUG DISCOVERY; SOLID TUMORS; SURGICAL CYTOREDUCTION; PANCREATIC-CANCER; ANTICANCER AGENTS AB Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching and viability, suggesting that it was a better reporter of PDT efficacy than total volume, which did not correlate with either metric. Based on these findings, live volume and viability are used to probe the susceptibilities of tumor populations to a range of PDT dose parameters administered using 0.25, 1, and 10 mu M benzoporphyrin derivative (BPD). PDT with 0.25 mu M BPD produces the most significant reduction in live volume and viability and mediates a substantial shift toward small nodules. Increasingly sophisticated bioengineered models may complement current treatment planning approaches and provide unique opportunities to critically evaluate key parameters including metrics of therapeutic response. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Anbil, Sriram; Rizvi, Imran; Celli, Jonathan P.; Alagic, Nermina; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. [Celli, Jonathan P.] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. [Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. EM thasan@mgh.harvard.edu OI Rizvi, Imran/0000-0001-9673-4700 FU National Cancer Institute; National Institutes of Health [1RC1CA146337, R01CA158415, R01CA1609998, R00CA155045] FX We would like to thank Ms. Sriya Anbil for advice regarding analysis of complex data sets, Dr. Akilan Palanisami for discussion regarding quantification of photosensitizer photobleaching, and Dr. Bryan Spring for advice regarding image processing. Dr. Hasan and Dr. Celli wish to acknowledge support from the National Cancer Institute and the National Institutes of Health: 1RC1CA146337 (T. H.), R01CA158415 (T. H.), R01CA1609998 (T. H.), and R00CA155045 (J.P.C.). NR 107 TC 11 Z9 11 U1 3 U2 12 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP PY 2013 VL 18 IS 9 AR 098004 DI 10.1117/1.JBO.18.9.098004 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AA6GY UT WOS:000331198000010 PM 24802230 ER PT J AU Spring, BQ Palanisami, A Zheng, LZ Blatt, AE Sears, RB Hasan, T AF Spring, Bryan Q. Palanisami, Akilan Zheng, Lei Zak Blatt, Amy E. Sears, R. Bryan Hasan, Tayyaba TI Efficient measurement of total tumor microvascularity ex vivo using a mathematical model to optimize volume subsampling SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE microvessel density; cancer; antivascular therapy; antiangiogenic therapy; photodynamic therapy; image analysis; fluorescence imaging; immunohistochemistry ID TYROSINE KINASE INHIBITOR; PHOTODYNAMIC THERAPY; IN-VIVO; ANTIANGIOGENIC THERAPY; MICROVESSEL DENSITY; BREAST-CARCINOMA; MOUSE-BRAIN; C-MET; CANCER; ANGIOGENESIS AB We introduce immunofluorescence and automated image processing protocols for serial tumor sections to objectively and efficiently quantify tumor microvasculature following antivascular therapy. To determine the trade-off between tumor subsampling and throughput versus microvessel quantification accuracy, we provide a mathematical model that accounts for tumor-specific vascular heterogeneity. This mathematical model can be applied broadly to define tumor volume samplings needed to reach statistical significance, depending on the biomarker in question and the number of subjects. Here, we demonstrate these concepts for tumor microvessel density and total microvascularity (TMV) quantification in whole pancreatic ductal adenocarcinoma tumors ex vivo. The results suggest that TMV is a more sensitive biomarker for detecting reductions in tumor vasculature following antivascular treatment. TMV imaging is a broadly accessible technique that offers robust assessment of antivascular therapies, and it offers promise as a tool for developing high-throughput assays to quantify treatment-induced microvascular alterations for therapeutic screening and development. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Spring, Bryan Q.; Palanisami, Akilan; Zheng, Lei Zak; Sears, R. Bryan; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. [Sears, R. Bryan] Emmanuel Coll, Dept Chem, Boston, MA USA. [Blatt, Amy E.; Hasan, Tayyaba] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Hasan, Tayyaba] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. EM thasan@mgh.harvard.edu FU US National Institutes of Health [P01-CA084203, R01-CA160998, F32-CA144210] FX We thank M. A. Gimbrone Jr. for a critical reading of the manuscript and insightful comments; I. Rizvi, L. A. Spring and R. P. Spring for helpful critiques; J. Zhao, J. LaGraves, E. Salomatina and P. Sherwood for expert technical assistance. This work was supported by US National Institutes of Health grants P01-CA084203 and R01-CA160998 to T. H. and F32-CA144210 to B. Q. S. NR 60 TC 2 Z9 2 U1 2 U2 4 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP PY 2013 VL 18 IS 9 AR 096015 DI 10.1117/1.JBO.18.9.096015 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AA6GY UT WOS:000331198000004 ER PT J AU Greve, DN Van der Haegen, L Cai, Q Stufflebeam, S Sabuncu, MR Fischl, B Brysbaert, M AF Greve, Douglas N. Van der Haegen, Lise Cai, Qing Stufflebeam, Steven Sabuncu, Mert R. Fischl, Bruce Brysbaert, Marc TI A Surface-based Analysis of Language Lateralization and Cortical Asymmetry SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID WORD FORM AREA; VENTRAL OCCIPITOTEMPORAL CORTEX; PLANUM TEMPORALE ASYMMETRY; HUMAN CEREBRAL-CORTEX; FUSIFORM FACE AREA; FUNCTIONAL MRI; GRAY-MATTER; BROCAS AREA; HEMISPHERIC-SPECIALIZATION; COORDINATE SYSTEM AB Among brain functions, language is one of the most lateralized. Cortical language areas are also some of the most asymmetrical in the brain. An open question is whether the asymmetry in function is linked to the asymmetry in anatomy. To address this question, we measured anatomical asymmetry in 34 participants shown with fMRI to have language dominance of the left hemisphere (LLD) and 21 participants shown to have atypical right hemisphere dominance (RLD). All participants were healthy and left-handed, and most (80%) were female. Gray matter (GM) volume asymmetry was measured using an automated surface-based technique in both ROIs and exploratory analyses. In the ROI analysis, a significant difference between LLD and RLD was found in the insula. No differences were found in planum temporale (PT), pars opercularis (POp), pars triangularis (PTr), or Heschl's gyrus (HG). The PT, POp, insula, and HG were all significantly left lateralized in both LLD and RLD participants. Both the positive and negative ROI findings replicate a previous study using manually labeled ROIs in a different cohort [Keller, S. S., Roberts, N., Garcia-Finana, M., Mohammadi, S., Ringelstein, E. B., Knecht, S., et al. Can the language-dominant hemisphere be predicted by brain anatomy? Journal of Cognitive Neuroscience, 23, 2013-2029, 2011]. The exploratory analysis was accomplished using a new surface-based registration that aligns cortical folding patterns across both subject and hemisphere. A small but significant cluster was found in the superior temporal gyrus that overlapped with the PT. A cluster was also found in the ventral occipitotemporal cortex corresponding to the visual word recognition area. The surface-based analysis also makes it possible to disentangle the effects of GM volume, thickness, and surface area while removing the effects of curvature. For both the ROI and exploratory analyses, the difference between LLD and RLD volume laterality was most strongly driven by differences in surface area and not cortical thickness. Overall, there were surprisingly few differences in GM volume asymmetry between LLD and RLD indicating that gross morphometric asymmetry is only subtly related to functional language laterality. C1 [Greve, Douglas N.; Stufflebeam, Steven; Sabuncu, Mert R.; Fischl, Bruce] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Van der Haegen, Lise; Cai, Qing; Brysbaert, Marc] Univ Ghent, B-9000 Ghent, Belgium. [Cai, Qing] E China Normal Univ, Shanghai, Peoples R China. [Cai, Qing] INSERM, Cognit Neuroimaging Unit, F-75654 Paris 13, France. [Sabuncu, Mert R.; Fischl, Bruce] MIT, Cambridge, MA 02139 USA. RP Greve, DN (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Room 2301,149 13th St, Charlestown, MA 02129 USA. EM greve@nmr.mgh.harvard.edu OI Brysbaert, Marc/0000-0002-3645-3189 FU National Institutes of Health [R01NS052585-03]; National Institute on Aging [5R01AG029411, 5R01AG022381-08]; National Institute of Neurological Disorders and Stroke [1R01NS069696-01A1]; National Center for Research Resources [P41-RR14075, R01 RR16594-01A1]; National Center for Research Resources (NCRR BIRN Morphometric Project) [BIRN002]; National Center for Research Resources (Functional Imaging Biomedical Informatics Research Network [FBIRN]) [U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550, R01 EB006758, 1K25 EB013649-01]; Government of Flanders FX Support for this research was provided in part by the National Institutes of Health (R01NS052585-03), the National Institute on Aging (5R01AG029411, 5R01AG022381-08), the National Institute of Neurological Disorders and Stroke (1R01NS069696-01A1), the National Center for Research Resources (P41-RR14075, R01 RR16594-01A1, the NCRR BIRN Morphometric Project BIRN002, and Functional Imaging Biomedical Informatics Research Network [FBIRN] U24 RR021382), and the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550, R01 EB006758, 1K25 EB013649-01). The scanning was made possible by an Odysseus Grant paid by the Government of Flanders to M.B. NR 83 TC 44 Z9 45 U1 6 U2 18 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 2013 VL 25 IS 9 BP 1477 EP 1492 DI 10.1162/jocn_a_00405 PG 16 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 301GB UT WOS:000330519700008 PM 23701459 ER PT J AU Platt, AB Wick, LC Hurley, S Soto-Calderon, H Wieland, W Staley, B Maislin, G Gurubhagavatula, I AF Platt, Alec B. Wick, Lindsay C. Hurley, Sharon Soto-Calderon, Haideliza Wieland, Will Staley, Beth Maislin, Greg Gurubhagavatula, Indira TI Hits and Misses Screening Commercial Drivers for Obstructive Sleep Apnea Using Guidelines Recommended by a Joint Task Force SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID MOTOR-VEHICLE CRASH; RISK; METAANALYSIS; ACCIDENTS; DIAGNOSIS; OBESITY; ADULTS AB Objective: To evaluate joint task force criteria-based screening for severe obstructive sleep apnea (s-OSA) in commercial drivers. Methods: Among a community-based cohort of licensed commercial vehicle drivers, we assessed utility of the joint task force criteria. We conducted full, 14-channel overnight polysomnography in all drivers, defining s-OSA as an apnea-hypopnea index of 30 or more per hour. Results: One hundred of 104 drivers with successful polysomnography studies were predominantly obese (median body mass index = 32.8 kg/m(2); interquartile range = 26.8 to 37.4) and had a median apnea-hypopnea index of 20.6 per hour (interquartile range = 10.0 to 34.2). Examination-based criteria were more effective (sensitivity = 80%; negative posttest probability [nPTP] = 17%) than symptom-based criteria (sensitivity = 63%; nPTP = 23%). Examination and symptom-based criteria combined had high sensitivity (97%) and low nPTP (7%), but poor specificity (19%). Conclusions: Examination-based criteria missed 20% of s-OSA cases. Combining examination with confidentially reported symptoms improved sensitivity but required confirmatory polysomnography in 86%, supporting universal screening of all drivers. C1 [Platt, Alec B.] Resp Specialists, Wyomissing, PA USA. [Platt, Alec B.; Gurubhagavatula, Indira] Univ Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19104 USA. [Wick, Lindsay C.; Hurley, Sharon; Soto-Calderon, Haideliza; Wieland, Will; Staley, Beth; Maislin, Greg; Gurubhagavatula, Indira] Univ Penn, Med Ctr, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Pulm Crit Care & Sleep Sect, Philadelphia, PA USA. RP Platt, AB (reprint author), 2608 Keiser Blvd, Wyomissing, PA 19610 USA. EM alecplatt@gmail.com FU NIOSH/CDC [R01-OH009149] FX The study was supported by NIOSH/CDC R01-OH009149. Embla Inc provided an unrestricted loan of sleep diagnostic equipment. NR 25 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD SEP PY 2013 VL 55 IS 9 BP 1035 EP 1040 DI 10.1097/JOM.0b013e318298fb0e PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 300EY UT WOS:000330448400007 PM 23969501 ER PT J AU Lawson, EH Hall, BL Ko, CY AF Lawson, Elise H. Hall, Bruce Lee Ko, Clifford Y. TI Risk Factors for Superficial vs Deep/Organ-Space Surgical Site Infections Implications for Quality Improvement Initiatives SO JAMA SURGERY LA English DT Article ID COLORECTAL SURGERY; WOUND-INFECTION; CARE; MORTALITY; PROGRAM; HOSPITALIZATION; SURVEILLANCE; ASSOCIATION; RESECTION; COLON AB IMPORTANCE Surgical site infections (SSIs) are the focus of numerous quality improvement initiatives because they are a common and costly cause of potentially preventable patient morbidity. Superficial and deep/organ-space SSIs differ in terms of anatomical location and clinical severity. OBJECTIVE To identify risk factors that are uniquely predictive of superficial vs deep/organ-space SSIs occurring after colectomy procedures. DESIGN Retrospective cohort study. SETTING American College of Surgeons National Surgical Quality Improvement Program. PARTICIPANTS Patients undergoing colectomy procedures in 2011 were identified by Current Procedural Terminology codes. INTERVENTION Colectomy procedures. MAIN OUTCOMES AND MEASURES We compared rates of superficial SSI and deep/organ-space SSI associated with perioperative variables of interest: demographics; preoperative clinical severity, risk factors, and comorbidities and variables related to the hospitalization or procedure. Hierarchical multivariable logistic regression models were developed to identify risk-adjusted predictors of each SSI type. RESULTS Among 27 011 patients identified from 305 hospitals, 6.2% developed a superficial SSI and 4.7% developed a deep/organ-space SSI. Risk factors common to the occurrence of both SSI types were identified: open surgery (vs laparoscopic) and current smoker. Risk factors with differential effects on each SSI type included specific postoperative diagnoses, disseminated cancer, and irradiation therapy, which were all associated with increased odds of deep/organ-space SSI only. The graded relationship between increasing body mass index and SSI occurrence appeared to be stronger for superficial SSI. CONCLUSIONS AND RELEVANCE Risk factors for superficial SSI and deep/organ-space SSI vary in terms of magnitude and significance, suggesting that these SSI types are somewhat different disease processes. Groups interested in preventing SSIs might improve success by considering these SSI types independently for root-cause analyses and development of best practices and interventions. C1 [Lawson, Elise H.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Hall, Bruce Lee] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hall, Bruce Lee] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Hall, Bruce Lee] St Louis Vet Affairs Med Ctr, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce Lee] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Hall, Bruce Lee; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Lawson, EH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM elawson@mednet.ucla.edu FU VA Health Services Research and Development program grant [RWJ 65-020]; ACS through the Robert Wood Johnson Foundation Clinical Scholars Program FX Dr Lawson's time was supported by VA Health Services Research and Development program grant RWJ 65-020 and the ACS through the Robert Wood Johnson Foundation Clinical Scholars Program. Dr Hall is a consultant for the ACS and Dr Ko is staff at the ACS. NR 30 TC 28 Z9 29 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD SEP PY 2013 VL 148 IS 9 BP 849 EP 858 DI 10.1001/jamasurg.2013.2925 PG 10 WC Surgery SC Surgery GA 228TE UT WOS:000325212300014 PM 23864108 ER PT J AU Cook, JM Pilver, C Dinnen, S Schnurr, PP Hoff, R AF Cook, Joan M. Pilver, Corey Dinnen, Stephanie Schnurr, Paula P. Hoff, Rani TI Prevalence of Physical and Sexual Assault and Mental Health Disorders in Older Women: Findings From a Nationally Representative Sample SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Geriatric; interpersonal violence; PTSD; women ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; TRAUMATIC EVENTS; COMORBIDITY-SURVEY; DOMESTIC VIOLENCE; VERBAL ABUSE; RISK-FACTORS; ADULTS; POPULATION; IMPACT AB Objectives: This study presents prevalence and characteristics of physical and sexual assaults, and their relationship to posttraumatic stress disorder (PTSD), and mood and anxiety disorders in a nationally representative sample of older women. Design and Setting: Face-to-face interviews conducted with adult participants from wave 2 of the National Epidemiological Survey on Alcohol and Related Conditions. Participants: A total of 3,354 community-residing women of age 65 years and older. Measurement: Alcohol Use Disorder and Associated Disabilities Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, current mood and anxiety disorders. Results: Almost 14% of participants reported a history of physical or sexual assault or both during their lifetimes. Assaults were often repeated rather than isolated events. Although the majority of participants did not identify interpersonal violence as their "worst" traumatic event, those who experienced interpersonal violence were generally more likely than those without such history to meet the criteria for past-year and lifetime PTSDs, depression, and anxiety. Conclusions: Some women who have been physically or sexually assaulted decades earlier continue to report significant levels of mood and anxiety disorders into late adulthood. Several ways to increase the identification and treatment of older female trauma survivors by healthcare providers are suggested. C1 [Cook, Joan M.; Pilver, Corey; Dinnen, Stephanie; Hoff, Rani] Yale Univ, Sch Med, New Haven, CT USA. [Cook, Joan M.; Schnurr, Paula P.] US Dept Vet Affairs, Natl Ctr PTSD, Washington, DC USA. [Schnurr, Paula P.] Geisel Sch Med, Dartmouth Med Sch, Hanover, NH USA. RP Cook, JM (reprint author), Yale Univ, Sch Med, Natl Ctr PTSD, NEPEC 182,950 Campbell Ave, West Haven, CT 06516 USA. EM Joan.Cook@yale.edu NR 41 TC 5 Z9 5 U1 7 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SEP PY 2013 VL 21 IS 9 BP 877 EP 886 DI 10.1016/j.jagp.2013.01.016 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 298YW UT WOS:000330361900009 PM 23567392 ER PT J AU Star, KV Ho, VT Wang, HH Odze, RD AF Star, Kremena V. Ho, Vincent T. Wang, Helen H. Odze, Robert D. TI Histologic Features in Colon Biopsies Can Discriminate Mycophenolate From GVHD-induced Colitis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE graft-versus-host disease; drug-induced colitis; toxic colitis; eosinophils; apoptosis; differential diagnosis ID VERSUS-HOST-DISEASE; MOFETIL-RELATED COLITIS; CADAVERIC RENAL-TRANSPLANTATION; VILLOUS ATROPHY; ACUTE REJECTION; GRAFT; RECIPIENTS; DRUG; CELL; PROPHYLAXIS AB Mycophenolate mofetil (MMF) is a T-cell inhibitor frequently used in the treatment of acute allograft rejection. MMF may cause colitis that clinically and histologically resembles graft-versus-host disease (GVHD). The aim of this study was to evaluate a wide range of histologic features that may help differentiate MMF from GVHD-induced colitis and to validate significant features on a cohort of bone marrow transplant patients who were also taking MMF as part of their immunosuppressive regimen and developed a diarrheal illness due to colitis. Routinely processed colonic biopsies from 17 patients with MMF colitis and 40 patients with GVHD-induced colitis were evaluated for the overall grade of colitis (grades 1 to 4) and histologically for a wide range of inflammatory, epithelial, and architectural changes in a blinded manner. Statistically significant features were then tested in a cohort of 20 bone marrow transplant patients who also received MMF, and later developed a diarrheal illness. Both univariate and multivariate analyses (including receiver operating characteristic analysis) were performed. Morphologic features shown to be independently associated with MMF include the presence and quantity of lamina propria eosinophils and endocrine cell aggregates and the presence and quantity of apoptotic microabscesses, hypereosinophilic (degenerated) crypts, and crypt distortion. Eosinophils were present in all MMF patients, but apoptotic microabscesses were present in none and endocrine cell aggregates in only 1 case. When a grade-by-grade comparison was made between MMF and GVHD, grade 1 or 2 MMF also showed an increased prevalence rate and quantity of lamina propria neutrophils in comparison with grade 1 or 2 GVHD. By receiver operating characteristic analysis, a combination of lamina propria eosinophils > 15 per 10 HPF, combined with a lack of endocrine cell aggregates and apoptotic microabscesses, revealed sensitivity, specificity, and positive and negative predictive values of 76%, 93%, 81%, and 90%, respectively, for identification of MMF colitis. On the basis of these data, we conclude that a variety of histologic features, in particular, eosinophils > 15 per 10 HPF, lack of endocrine cell aggregates in the lamina propria, and lack of apoptotic microabscesses, can be used by pathologists to help separate MMF from GVHD-induced colitis in routine clinical practice. C1 [Star, Kremena V.; Odze, Robert D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wang, Helen H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Odze, RD (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM rodze@partners.org NR 38 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2013 VL 37 IS 9 BP 1319 EP 1328 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 299XU UT WOS:000330429800003 PM 24076772 ER PT J AU Abdel-Mesih, A Daya, D Onuma, K Sur, M Tang, SG Akhtar-Danesh, N Boutross-Tadross, O Ceballos, KM Chapman, W Colgan, T Deb, P Nucci, MR Oliva, E Lytwyn, A AF Abdel-Mesih, Amal Daya, Dean Onuma, Kazu Sur, Monalisa Tang, Shangguo Akhtar-Danesh, Noori Boutross-Tadross, Odette Ceballos, Kathy M. Chapman, William Colgan, Terence Deb, Pratima Nucci, Marisa R. Oliva, Esther Lytwyn, Alice TI Interobserver Agreement for Assessing Invasion in Stage 1A Vulvar Squamous Cell Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE vulva; squamous cell carcinoma; stage 1A; depth of invasion; interobserver agreement ID NODE DISSECTION; CANCER; REPRODUCIBILITY; IA AB Invasive squamous cell carcinoma of the vulva with <= 1mm stromal invasion is classified as stage 1A. Cancer staging systems state that the depth of invasion should be measured from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of the invasive tumor. Measurement of the depth of invasion guides patient management. Even though this measurement is critical, no studies have reported the reliability among pathologists for determining the cutoff point of <= 1mm stromal invasion in vulvar cancer. We assessed agreement among pathologists for determining whether a vulvar tumor is invasive, for the depth of invasion, and for tumor thickness. Forty-five cases of vulvar squamous cell carcinoma with a depth of invasion of <= 5mm were chosen. Eleven gynecologic pathologists independently reviewed the slides and, for a subset of cases, pictorially recorded measurements on photographs. The number of cases that were reported as invasive by the 11 pathologists ranged from 21 to 44. The number of cases that were reported as showing a depth of invasion of <= 1mm ranged from 7 to 27. Eight pathologists provided measurements for all lesions reported as invasive, the remaining 3 pathologists stated that they were unable to measure 2, 7, and 16 lesions, respectively. Mean kappa for diagnosing vulvar carcinoma as invasive was 0.24 and for measuring the depth of invasion and thickness was 0.51 and 0.49, respectively. There was only fair agreement in determining whether the lesion was invasive. In cases in which pathologists agreed upon the diagnosis of invasion, agreement on depth was moderate. When using the recommended cancer staging method, interpretation of the location of the most superficial dermal papilla varied among pathologists. Measuring thickness did not improve agreement. This is the first study that has assessed the reliability of the diagnosis of invasion in vulvar cancer among gynecologic pathologists, the interobserver agreement for reporting the critical 1mm threshold of depth of stromal invasion, and the way in which the International Federation of Gynecology and Obstetrics method is used by pathologists. C1 [Abdel-Mesih, Amal; Daya, Dean; Onuma, Kazu; Sur, Monalisa; Tang, Shangguo; Deb, Pratima; Lytwyn, Alice] Juravinski Hosp, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Akhtar-Danesh, Noori] McMaster Univ, Sch Nursing, Hamilton, ON, Canada. [Akhtar-Danesh, Noori; Lytwyn, Alice] McMaster Univ, Med Ctr, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Boutross-Tadross, Odette] McMaster Univ, Med Ctr, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Chapman, William] St Josephs Hosp, Dept Pathol, Toronto, ON, Canada. [Colgan, Terence] Univ Toronto, Mt Sinai Hosp, Dept Pathol, Toronto, ON M5G 1X5, Canada. [Ceballos, Kathy M.] Univ British Columbia, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. [Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Oliva, Esther] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Abdel-Mesih, A (reprint author), St Josephs Hosp, Dept Pathol & Mol Med, 50 Charlton Ave East, Hamilton, ON L8N 4A6, Canada. EM amal.abdel-mesih@medportal.ca RI Colgan, Terence/J-2339-2016 NR 22 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2013 VL 37 IS 9 BP 1336 EP 1341 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 299XU UT WOS:000330429800005 PM 24076774 ER PT J AU Hoang, LN McConechy, MK Kobel, M Han, GM Rouzbahman, M Davidson, B Irving, J Ali, RH Leung, S McAlpine, JN Oliva, E Nucci, MR Soslow, RA Huntsman, DG Gilks, CB Lee, CH AF Hoang, Lien N. McConechy, Melissa K. Koebel, Martin Han, Guangming Rouzbahman, Marjan Davidson, Ben Irving, Julie Ali, Rola H. Leung, Sam McAlpine, Jessica N. Oliva, Esther Nucci, Marisa R. Soslow, Robert A. Huntsman, David G. Gilks, C. Blake Lee, Cheng-Han TI Histotype-Genotype Correlation in 36 High-grade Endometrial Carcinomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial cancer; serous carcinoma; endometrioid; carcinoma; ARID1A; PTEN; PPP2R1A; TP53 ID CLEAR-CELL CARCINOMA; SEROUS CARCINOMAS; SOMATIC MUTATIONS; P16 EXPRESSION; CANCER; OVARIAN; ARID1A; ADENOCARCINOMA; STRATEGIES; AGREEMENT AB Endometrioid, serous, and clear cell carcinomas are the major types of endometrial carcinoma. Histologic distinction between these different tumor types can be difficult in high-grade cases, in which significant interobserver diagnostic disagreement exists. Endometrioid and clear cell carcinomas frequently harbor ARID1A and/or PTEN mutations. Serous carcinoma acquires TP53 mutations/inactivation at onset, with a significant subset harboring an additional mutation in PPP2R1A. This study examines the correlation between tumor histotype and genotype in 36 previously genotyped high-grade endometrial carcinomas. This included 23 endometrioid/clear cell genotype and 13 serous genotype tumors. Eight subspecialty pathologists reviewed representative online slides and rendered diagnoses before and after receiving p53, p16, and estrogen receptor immunostaining results. kappa statistics for histotype-genotype concordance were calculated. The average k values for histotype-genotype concordance was 0.55 (range, 0.30 to 0.67) on the basis of morphologic evaluation alone and it improved to 0.68 (range, 0.54 to 0.81) after immunophenotype consideration (P < 0.001). Genotype-incompatible diagnoses were rendered by at least 2 pathologists in 12 of 36 cases (33%) (3 cases by 2/8 pathologists, 2 by 3/8, 2 by 4/8, 3 by 6/8, 1 by 7/8, and 1 case by 8/8 pathologists). Six of the 12 were endometrioid/clear cell genotype tumors, and the other 6 were serous genotype tumors. The histopathologic features associated with histotype-genotype-discordant cases were reviewed, and specific diagnostic recommendations were made to improve concordance. This study found that although the majority of morphologic diagnoses are genotype concordant, genotype-incompatible diagnoses are made in a significant subset of cases. Judicious use and interpretation of p53 immunohistochemistry in selected scenarios can improve histotype-genotype concordance. C1 [Hoang, Lien N.; McConechy, Melissa K.; Irving, Julie; Ali, Rola H.; Leung, Sam; Huntsman, David G.; Gilks, C. Blake; Lee, Cheng-Han] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E3, Canada. [McAlpine, Jessica N.] Univ British Columbia, Dept Gynecol & Obstet, Vancouver, BC V5Z 4E3, Canada. [Hoang, Lien N.; McConechy, Melissa K.; Irving, Julie; Ali, Rola H.; Leung, Sam; Huntsman, David G.; Gilks, C. Blake; Lee, Cheng-Han] Vancouver Gen Hosp, Genet Pathol Evaluat Ctr, Vancouver, BC, Canada. [Koebel, Martin] Univ Calgary, Dept Pathol, Calgary, AB, Canada. [Han, Guangming; Rouzbahman, Marjan] Univ Toronto, Dept Pathol, Toronto, ON, Canada. [Davidson, Ben] Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Fac Med, Oslo, Norway. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Lee, CH (reprint author), Univ British Columbia, Dept Pathol & Lab Med, JP1400,910 West 10th Ave, Vancouver, BC V5Z 4E3, Canada. EM chenghanlee@gmail.com OI Ali, Rola/0000-0001-5747-8900; Kobel, Martin/0000-0002-6615-2037 FU British Columbia (BC) Cancer Foundation; Vancouver General Hospital (VGH)-University of British Columbia Hospital Foundation FX Supported by grants from the British Columbia (BC) Cancer Foundation and the Vancouver General Hospital (VGH)-University of British Columbia Hospital Foundation (to the OvCaRe ovarian cancer research team in Vancouver) and the Canadian Institutes of Health Research (CIHR). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 38 TC 32 Z9 32 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2013 VL 37 IS 9 BP 1421 EP 1432 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 299XU UT WOS:000330429800017 PM 24076778 ER PT J AU Sholl, LM Sun, H Butaney, M Zhang, CS Lee, C Janne, PA Rodig, SJ AF Sholl, Lynette M. Sun, Heather Butaney, Mohit Zhang, Chengsheng Lee, Charles Jaenne, Pasi A. Rodig, Scott J. TI ROS1 Immunohistochemistry for Detection of ROS1-Rearranged Lung Adenocarcinomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ROS1; lung adenocarcinoma; immunohistochemistry ID CANCER; CRIZOTINIB; MUTATIONS; GEFITINIB; RECEPTOR; THERAPY; EGFR AB ROS1 gene rearrangements are reported in 1% to 2% of lung adenocarcinomas (ACAs) and are associated with response to the multitargeted tyrosine kinase inhibitor crizotinib. ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH); however, immunohistochemistry (IHC) for ROS1 protein is a promising alternate screening modality. In this study, we examine the correlation between ROS1 IHC and FISH and describe the clinicopathologic characteristics of ROS1-rearranged lung tumors. ROS1 IHC was performed using clone D4D6 on whole-tissue sections. In a validation cohort, IHC was compared with ROS1 break-apart FISH in 53 cases of lung ACA enriched for an absence of known genetic alterations and never-smoking status. In a screening cohort, we performed ROS1 IHC on 167 consecutive cases of lung ACA from a routine molecular diagnostic practice and confirmed positive results by FISH. In the validation cohort, 6 cases (11%) were both FISH and IHC positive. One FISH-negative case was strongly ROS1 IHC positive. All IHC-negative cases were FISH negative. In the screening cohort, 2 of 167 (1.2%) had strong, diffuse ROS1 protein expression; a rearrangement was confirmed by FISH in both. ROS1-translocated tumors were wild type for EGFR, KRAS, and ALK and commonly had solid growth with mucinous/cribriform features and psammomatous calcification. ROS1 protein expression in tumor cells is 100% sensitive and 92% specific for ROS1 rearrangements by FISH. ROS1 IHC is an effective screening tool for this rare but clinically important subset of lung ACAs. C1 [Sholl, Lynette M.; Sun, Heather; Zhang, Chengsheng; Lee, Charles; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Butaney, Mohit; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. RP Sholl, LM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lmsholl@partners.org FU Ventana Medical Systems Inc.; Genentech; National Institutes of Health [P50 CA090578]; Pfizer; Boehringer Ingelheim; Roche; Sanofi; Astra Zeneca; Chugai Pharmaceuticals; Lab Corp. FX Cell Signaling Technology Inc. provided ROS1 immunohistochemistry reagents under a research agreement with Brigham and Women's Hospital and Dana Farber Cancer Institute. L. M. S. received travel funding from Ventana Medical Systems Inc. and receives consultancy fees from Genentech. P.A.J. is currently receiving a grant (#P50 CA090578) from the National Institutes of Health and receives consultancy fees from Pfizer, Boehringer Ingelheim, Roche, Sanofi, Astra Zeneca, and Chugai Pharmaceuticals and royalties from Lab Corp. For the remaining authors none were declared. NR 20 TC 47 Z9 48 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2013 VL 37 IS 9 BP 1441 EP 1449 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 299XU UT WOS:000330429800019 PM 23887156 ER PT J AU McCluggage, WG Staats, PN Gilks, CB Clement, PB Young, RH AF McCluggage, W. Glenn Staats, Paul N. Gilks, C. Blake Clement, Philip B. Young, Robert H. TI Luteinized Thecomas (Thecomatosis) Associated With Sclerosing Peritonitis Exhibit Positive Staining With Sex Cord Markers Steroidogenic Factor-1 (SF-1) and FOXL2 SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter ID USEFUL IMMUNOHISTOCHEMICAL MARKER; GRANULOSA-CELL TUMORS; STROMAL TUMORS; DIAGNOSIS; INHIBIN; OVARY C1 [McCluggage, W. Glenn] Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland. [Staats, Paul N.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gilks, C. Blake; Clement, Philip B.] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. [Gilks, C. Blake; Clement, Philip B.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP McCluggage, WG (reprint author), Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland. NR 11 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2013 VL 37 IS 9 BP 1458 EP 1459 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA 299XU UT WOS:000330429800022 PM 24076780 ER PT J AU DeMatteo, RP Ballman, KV Antonescu, CR Corless, C Kolesnikova, V von Mehren, M McCarter, MD Norton, J Maki, RG Pisters, PWT Demetri, GD Brennan, MF Owzar, K AF DeMatteo, Ronald P. Ballman, Karla V. Antonescu, Cristina R. Corless, Christopher Kolesnikova, Violetta von Mehren, Margaret McCarter, Martin D. Norton, Jeffrey Maki, Robert G. Pisters, Peter W. T. Demetri, George D. Brennan, Murray F. Owzar, Kouros CA ACOSOG TI Long-term Results of Adjuvant Imatinib Mesylate in Localized, High-Risk, Primary Gastrointestinal Stromal Tumor ACOSOG Z9000 (Alliance) Intergroup Phase 2 Trial SO ANNALS OF SURGERY LA English DT Article DE gastrointestinal stromal tumor; imatinib mesylate; surgery ID PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; DOSE IMATINIB; KIT; MUTATIONS; SURVIVAL; MANAGEMENT; LEIOMYOSARCOMAS; RECURRENCE; PATTERNS AB Objective: To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST). Background: GIST is the most common sarcoma. Although surgical resection has been the mainstay of therapy for localized, primary GIST, postoperative tumor recurrence is common. The KIT protooncogene or, less frequently, platelet-derived growth factor receptor alpha is mutated in GIST; the gene products of both are inhibited by imatinib mesylate. Methods: This was a phase II, intergroup trial led by the American College of Surgeons Oncology Group, registered at ClinicalTrials. gov as NCT00025246. From September 2001 to September 2003, we accrued 106 patients who had undergone complete gross tumor removal but were deemed at high risk for recurrence. Patients were prescribed imatinib 400 mg per day for 1 year and followed with serial radiologic evaluation. The primary endpoint was overall survival (OS). Results: After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rates were 99%, 97%, and 83%, which compared favorably with a historical 5-year OS rate of 35%. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 96%, 60%, and 40%. On univariable analysis, age and mitotic rate were associated with OS. On multivariable analysis, the RFS rate was lower with increasing tumor size, small bowel site, KIT exon 9 mutation, high mitotic rate, and older age. Conclusions: Adjuvant imatinib in patients with primary GIST who are at high risk of recurrence prolongs OS compared with that of historical controls. Optimal duration of adjuvant therapy remains undefined. (NCT00025246) C1 [DeMatteo, Ronald P.; Antonescu, Cristina R.; Brennan, Murray F.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Ballman, Karla V.] Alliance Stat, Rochester, MN USA. [Ballman, Karla V.] Mayo Clin, Ctr Data, Rochester, MN USA. [Corless, Christopher; Kolesnikova, Violetta] Oregon Hlth & Sci Univ, Portland, OR USA. [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [McCarter, Martin D.] Univ Colorado, Sch Med, Aurora, CO USA. [Norton, Jeffrey] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Maki, Robert G.] Mt Sinai Sch Med, New York, NY USA. [Pisters, Peter W. T.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Owzar, Kouros] Alliance Stat, Durham, NC USA. [Owzar, Kouros] Duke Univ, Ctr Data, Durham, NC USA. RP DeMatteo, RP (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM dematter@mskcc.org OI Brennan, Murray/0000-0003-2358-4371 FU National Cancer Institute [U10 CA076001, CA94503, CA102613, CA31946, CA33601]; Society of Surgical Oncology FX This work was supported by grants U10 CA076001 (ACOSOG) and CA94503 and CA102613 (R. P. D.) from the National Cancer Institute. The research for ACOSOG Z9000 (Alliance) was also supported, in part, by grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair) and to the Alliance Statistics and Data Center (Daniel J. Sargent, PhD, CA33601). Dr DeMatteo was the recipient of a Clinical Investigator Award from the Society of Surgical Oncology. ACOSOG Z9000 was conducted through a contract between Novartis and National Cancer Institute under CRADA 1111.1. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Drs DeMatteo, Corless, von Mehren Maki, Pisters, and Demetri report receiving honoraria from Novartis and have served on Novartis advisory boards. No other relevant conflicts of interest were reported. NR 23 TC 38 Z9 39 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2013 VL 258 IS 3 BP 422 EP 429 DI 10.1097/SLA.0b013e3182a15eb7 PG 8 WC Surgery SC Surgery GA 300KX UT WOS:000330463900006 PM 23860199 ER PT J AU Sahora, K Mino-Kenudson, M Brugge, W Thayer, SP Ferrone, CR Sahani, D Pitman, MB Warshaw, AL Lillemoe, KD Fernandez-del Castillo, CF AF Sahora, Klaus Mino-Kenudson, Mari Brugge, William Thayer, Sarah P. Ferrone, Cristina R. Sahani, Dushyant Pitman, Martha B. Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos F. TI Branch Duct Intraductal Papillary Mucinous Neoplasms Does Cyst Size Change the Tip of the Scale? A Critical Analysis of the Revised International Consensus Guidelines in a Large Single-Institutional Series SO ANNALS OF SURGERY LA English DT Article DE guidelines; intraductal papillary mucinous neoplasm; malignancy; pancreas; pancreatic cystic neoplasm; surgery ID MURAL NODULES; PANCREAS; MANAGEMENT; RESECTION; MALIGNANCY; OPERATE AB Objective: The aim of this study was to critically analyze the safety of the revised guidelines, with focus on cyst size and worrisome features in the management of BD-IPMN. Background: The Sendai guidelines for management of branch duct (BD) intraductal papillary mucinous neoplasm (IPMN) espouse safety of observation of asymptomatic cysts smaller than 3 cm without nodules (Sendai negative). Revised international consensus guidelines published in 2012 suggest a still more conservative approach, even for lesions of 3 cm or larger. By contrast, 2 recent studies have challenged the safety of both guidelines, describing invasive carcinoma or carcinoma in situ in 67% of BD-IPMN smaller than 3 cm and in 25% of "Sendai-negative" BD-IPMN. Methods and Results: Review of a prospective database identified 563 patients with BD-IPMN. A total of 240 patients underwent surgical resection (152 at the time of diagnosis and 88 after being initially followed); the remaining 323 have been managed by observation with median follow-up of 60 months. No patient developed unresectable BD-IPMN carcinoma during follow-up. Invasive cancer arising in BD-IPMN was found in 23 patients of the entire cohort (4%), and an additional 21 patients (3.7%) had or developed concurrent pancreatic ductal adenocarcinoma. According to the revised guidelines, 76% of resected BD-IPMN with carcinoma in situ and 95% of resected BD-IPMN with invasive cancer had high-risk stigmata or worrisome features. The risk of high-grade dysplasia in nonworrisome lesions smaller than 3 cm was 6.5%, but when the threshold was raised to greater than 3 cm, it was 8.8%, and 1 case of invasive carcinoma was found. Conclusions: Expectant management of BD-IPMN following the old guidelines is safe, whereas caution is advised for larger lesions, even in the absence of worrisome features. C1 [Sahora, Klaus; Thayer, Sarah P.; Ferrone, Cristina R.; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Pitman, Martha B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brugge, William] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Sahani, Dushyant] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Fernandez-del Castillo, CF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU Austrian Society of Surgery FX Klaus Sahora was supported by a Grant by the Austrian Society of Surgery. The authors declare no conflicts of interest. NR 26 TC 85 Z9 86 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2013 VL 258 IS 3 BP 466 EP 475 DI 10.1097/SLA.0b013e3182a18f48 PG 10 WC Surgery SC Surgery GA 300KX UT WOS:000330463900011 PM 24022439 ER PT J AU Pitt, HA Sherman, S Johnson, MS Hollenbeck, AN Lee, J Daum, MR Lillemoe, KD Lehman, GA AF Pitt, Henry A. Sherman, Stuart Johnson, Matthew S. Hollenbeck, Andrew N. Lee, Jonathan Daum, Michael R. Lillemoe, Keith D. Lehman, Glen A. TI Improved Outcomes of Bile Duct Injuries in the 21st Century SO ANNALS OF SURGERY LA English DT Article DE bile duct injury; bile duct stricture; bile leak and cholecystectomy ID BENIGN BILIARY STRICTURES; HEPATIC-ARTERY INJURY; QUALITY-OF-LIFE; LAPAROSCOPIC CHOLECYSTECTOMY; SURGICAL REPAIR; RISK-FACTORS; MANAGEMENT; COMPLICATIONS; RECONSTRUCTION; SURGERY AB Objective: The objectives of this analysis were to compare the outcomes of bile duct injuries by specialist over time and the role of management timing and biliary stents. Background: Postoperative bile duct injuries require multidisciplinary management. In recent years, advancements have occurred in patient evaluation and in timing and type of therapy. Methods: A multidisciplinary team managed 528 patients over 18 years. Mean age was 52 years; 69% were women and 95% had a cholecystectomy and/or bile duct exploration. Patients were classified by the Strasberg system as having bile leaks (type A, n = 239, 45%) or bile duct injuries (types B-E, n = 289, 55%). Injury outcomes from 1993 to 2003 (n = 132) were compared with those from 2004 to 2010 (n = 157). A successful outcome was defined as no need for further intervention after the initial 12 months of therapy. Standard statistical methods were employed. Results: Patients with bile leaks were managed almost exclusively by endoscopists (96%) with a 96% success rate. Patients with bile duct injuries were managed most often by endoscopists (N = 115, 40%) followed by surgeons (N = 104, 36%) and interventional radiologists (N = 70, 24%). Overall success rates were best for surgery (88%, P < 0.05) followed by endoscopy (76%) and interventional radiology (50%) and improved over time (78% vs 69%). Outcomes were best for surgery in recent years (95% vs 80%, P < 0.05) and for patients stented for more than 6 months (P < 0.01). Conclusions: Almost all bile leaks and many bile duct injuries can be managed successfully by endoscopists. Selected proximal injuries can be treated by interventional radiologists with modest success. Outcomes of bile duct injuries are best with surgical management and in patients who are stented for more than 6 months. C1 [Pitt, Henry A.; Hollenbeck, Andrew N.; Lee, Jonathan; Daum, Michael R.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Sherman, Stuart; Lehman, Glen A.] Indiana Univ Sch Med, Div Gastroenterol, Indianapolis, IN 46202 USA. [Johnson, Matthew S.] Indiana Univ Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. [Lillemoe, Keith D.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Pitt, HA (reprint author), Temple Univ Hlth Syst, 3509 N Broad St,Boyer Pavil,E938, Philadelphia, PA 19140 USA. EM Henry.Pitt@tuhs.temple.edu NR 45 TC 16 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2013 VL 258 IS 3 BP 490 EP 499 DI 10.1097/SLA.0b013e3182a1b25b PG 10 WC Surgery SC Surgery GA 300KX UT WOS:000330463900014 PM 24022441 ER PT J AU Loscalzo, M Clark, K Pal, S Pirl, WF AF Loscalzo, Matthew Clark, Karen Pal, Sumanta Pirl, William F. TI Role of Biopsychosocial Screening in Cancer Care SO CANCER JOURNAL LA English DT Review DE Cancer; biopsychosocial; distress; problem based; screening; supportive care; psychosocial standards ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-SERVICE USE; 6TH VITAL SIGN; LUNG-CANCER; PSYCHOLOGICAL DISTRESS; MEDICAL ONCOLOGISTS; PALLIATIVE CARE; PATIENT; QUALITY; RECOGNITION AB This review focuses on the aspects of biopsychosocial screening that have specific and significant implications for supportive care related to cancer care and research. There is a robust literature relating to the unmet supportive care needs of cancer patients and their families and the clinical interventions needed to effectively manage many of their problems. The Zeitgeist movement, which promotes the idea that the resources of this planet are the inherent right of all peoples, is also uniquely aligned to see supportive care services in oncology bringing significant value ( cost and quality) to a health care system that is experiencing great uncertainty. Overall, there is a broadening of perspective within the supportive care community that there needs to be greater levels of interdisciplinary integration. More significantly, there is a growing realization that for cancer care to be truly patient and family centered and even minimally efficient, disease-directed care and supportive care need to be integrated from the time of diagnosis. The coordination of these services should not be based on the stage of the disease but rather tailored to the needs of the patient, family, and social context. Biopsychosocial screening programs have the potential to be the connective tissue of these patient- and family-centered systems. C1 [Loscalzo, Matthew; Clark, Karen] City Hope Natl Med Ctr, Support Care Programs, Duarte, CA USA. [Pal, Sumanta] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA. [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA USA. RP Loscalzo, M (reprint author), City Hope Natl Med Ctr, LCSW, 1500 E Duarte Rd,Main Med Bldg,Suite Y-1, Duarte, CA 91010 USA. EM Mloscalzo@COH.org NR 55 TC 1 Z9 1 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD SEP-OCT PY 2013 VL 19 IS 5 BP 414 EP 420 PG 7 WC Oncology SC Oncology GA 300OW UT WOS:000330474300008 PM 24051615 ER PT J AU Al-Gallas, N Abbassi, MS Gharbi, B Manai, M Ben Fayala, MN Bichihi, R Al-Gallas, A Ben Aissa, R AF Al-Gallas, Nazek Abbassi, Mohamed Salah Gharbi, Becher Manai, Molka Ben Fayala, Mohamed N. Bichihi, Raghda Al-Gallas, Amna Ben Aissa, Ridha TI Occurrence of Plasmid-Mediated Quinolone Resistance Determinants and rmtB Gene in Salmonella enterica Serovar Enteritidis and Typhimurium Isolated from Food-Animal Products in Tunisia SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FIELD GEL-ELECTROPHORESIS; ANTIMICROBIAL RESISTANCE; ESCHERICHIA-COLI; MODIFYING ENZYME; VIRULENCE GENES; UNITED-STATES; POULTRY; HUMANS; PREVALENCE; MECHANISMS AB Four hundred and thirty Salmonella isolates, recovered from various food-animal products, were tested for nalidixic acid resistance, plasmid-mediated quinolone resistance, and genetic relationship. One hundred fifteen isolates (113 Salmonella serovar Enteritidis and two Salmonella serovar Typhimurium isolates) of 430 (26.7%) Salmonella isolates exhibited nalidixic acid resistance. Polymerase chain reaction screening for qnrA, qnrB, qnrS, qepA (encoding fluoroquinolones resistance) and rmtB (encoding aminoglycosides resistance) showed that 5 (1.16%) isolates were positive for qnr- and qepA-type genes, and the aac(6')-Ib-cr gene was observed in two (1.7%) Enteritidis isolates concomitantly with qnrA or qnrB. The co-occurrence of qepA and rmtB in one Typhimurium isolate is noteworthy. Pulsed-field gel electrophoresis revealed a high genetic homogeneity of nalidixic-resistant isolates and the persistence of clonal clusters over 4 years in different regions in Tunisia and from various food-animal products. To the best of our knowledge, this is the first report of co-occurrence of qepA and rmtB in a Salmonella C1 [Al-Gallas, Nazek; Gharbi, Becher; Manai, Molka; Ben Fayala, Mohamed N.; Bichihi, Raghda; Ben Aissa, Ridha] Inst Pasteur Tunis, Lab Controle Eaux & Denrees Alimentaires, Ctr Natl Salmonella Shigella & Vibrio Spp, Tunis 1002, Tunisia. [Abbassi, Mohamed Salah] Inst Rech Vet Tunisie, Lab Rech Bacteriol, Tunis, Tunisia. [Al-Gallas, Amna] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Ben Aissa, R (reprint author), Inst Pasteur Tunis, 13 Pl Pasteur,BP 74, Tunis 1002, Tunisia. EM ridha.benaissa@pasteur.rns.tn NR 47 TC 3 Z9 3 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 EI 1556-7125 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD SEP PY 2013 VL 10 IS 9 BP 813 EP 819 DI 10.1089/fpd.2012.1466 PG 7 WC Food Science & Technology SC Food Science & Technology GA 300IF UT WOS:000330456900010 PM 23767853 ER PT J AU Rauh-Hain, JA Guseh, SH Esselen, KM Growdon, WB Schorge, JO Horowitz, NS Krasner, CN del Carmen, MG Birrer, MJ Dizon, DS AF Rauh-Hain, Jose Alejandro Guseh, Stephanie H. Esselen, Katharine M. Growdon, Whitfield B. Schorge, John O. Horowitz, Neil S. Krasner, Carolyn N. del Carmen, Marcela G. Birrer, Michael J. Dizon, Don S. TI Patterns of Recurrence in Patients Treated With Bevacizumab in the Primary Treatment of Advanced Epithelial Ovarian Cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Bevacizumab; Recurrence; Epithelial ovarian cancer ID INTRAPERITONEAL CHEMOTHERAPY; COLORECTAL-CANCER; METASTASES; CARCINOMA AB Objective: The purpose of this study was to compare the distribution of the first site of recurrence in patients with epithelial ovarian cancer (EOC) who received first-line treatment with bevacizumab compared with patients who did not receive bevacizumab. Methods: From the Cancer Registry database at our institutions, we identified a group of patients with recurrent EOC who underwent treatment from January 1, 2005, to December 31, 2010. Each patient record was evaluated to classify the site of first recurrence. Correlation between categorical variables was assessed with W 2 test. Results: Two hundred ninety-two patients with advanced EOC (stage III or IV) who originally responded to chemotherapy and had a recurrence were identified. Of these, 37 (12.5%) had received postoperative chemotherapy bevacizumab, and 255 (87.5%) did not. Compared with those not treated with bevacizumab, there was a lower incidence of liver recurrence (0% vs 9%; P = 0.05) and a higher rate of lung and/or pleural recurrence (22% vs 5%; P = 0.001) and recurrence at distant sites (22% vs 9%; P = 0.03) in patients who received bevacizumab. There was no difference in the incidence of ascites at the time of recurrence between these groups. Conclusions: Patients who received bevacizumab as part of primary treatment for EOC had a higher rate of lung and/or pleural recurrence and a lower rate of liver recurrence. There was no difference in the rate of ascites at the time of recurrence. C1 [Rauh-Hain, Jose Alejandro; Guseh, Stephanie H.; Growdon, Whitfield B.; Schorge, John O.; del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Guseh, Stephanie H.; Esselen, Katharine M.; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. [Krasner, Carolyn N.; Birrer, Michael J.; Dizon, Don S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Dizon, DS (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ddizon@partners.org NR 20 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP PY 2013 VL 23 IS 7 BP 1219 EP 1225 DI 10.1097/IGC.0b013e31829f17c9 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 299CW UT WOS:000330373700011 PM 23975042 ER PT J AU Schlett, CL Maurovich-Horvat, P Ferencik, M Alkadhi, H Stolzmann, P Scheffel, H Seifarth, H Nakano, M Do, S Vorpahl, M Kauczor, HU Bamberg, F Tearney, GJ Virmani, R Hoffmann, U AF Schlett, Christopher L. Maurovich-Horvat, Pal Ferencik, Maros Alkadhi, Hatem Stolzmann, Paul Scheffel, Hans Seifarth, Harald Nakano, Masataka Do, Synho Vorpahl, Marc Kauczor, Hans-Ulrich Bamberg, Fabian Tearney, Guillermo J. Virmani, Renu Hoffmann, Udo TI Histogram Analysis of Lipid-Core Plaques in Coronary Computed Tomographic Angiography Ex Vivo Validation Against Histology SO INVESTIGATIVE RADIOLOGY LA English DT Article DE coronary CT angiography; quantitative histogram analysis; low attenuation plaque; lipid-core plaque; optical coherence tomography; histology ID OPTICAL COHERENCE TOMOGRAPHY; ATHEROSCLEROTIC PLAQUES; INTRAVASCULAR ULTRASOUND; DIAGNOSTIC-ACCURACY; VULNERABLE PLAQUE; PROGNOSTIC VALUE; ARTERY-DISEASE; CHEST-PAIN; CT; LESIONS AB Purpose: In coronary computed tomographic angiography (CTA), low attenuation of coronary atherosclerotic plaque is associated with lipid-rich plaques. However, an overlap in Hounsfield units (HU) between fibrous and lipid-rich plaque as well as an influence of luminal enhancement on plaque attenuation was observed and may limit accurate detection of lipid-rich plaques by CTA. We sought to determine whether the quantitative histogram analysis improves accuracy of the detection of lipid-core plaque (LCP) in ex vivo hearts by validation against histological analysis. Materials and Methods: Human donor hearts were imaged with a 64-slice computed tomographic scanner using a standard coronary CTA protocol, optical coherence tomography (OCT), a histological analysis. Lipid-core plaque was defined in the histological analysis as any fibroatheroma with a lipid/necrotic core diameter of greater than 200 Km and a circumference greater than 60 degrees as well as a cap thickness of less than 450 mu m. In OCT, lipid-rich plaque was determined as a signal-poor region with diffuse borders in 2 quadrants or more. In CTA, the boundaries of the noncalcified plaque were manually traced. The absolute and relative areas of low attenuation plaque based on pixels with less than 30, less than 60, and less than 90 HU were calculated using quantitative histogram analysis. Results: From 5 hearts, a total of 446 cross sections were coregistered between CTA and the histological analysis. Overall, 55 LCPs (12%) were identified by the histological analysis. In CTA, the absolute and relative areas of low attenuation plaque less than 30, less than 60, and less than 90 HU were 0.14 (0.31) mm(2) (4.22% [9.02%]), 0.69 (0.95) mm(2) (18.28% [21.22%]), and 1.35 (1.54) mm(2) (35.65% [32.07%]), respectively. The low attenuation plaque area correlated significantly with histological lipid content (lipid/necrotic core size [in square millimeter] and a portion of lipid/necrotic core on the entire plaque) at all thresholds but was the strongest at less than 60 HU (r = 0.53 and r = 0.48 for the absolute and relative areas, respectively). Using a threshold of 1.0 mm(2) or greater, the absolute plaque area of less than 60 HU in CTA yielded 69% sensitivity and 80% specificity to detect LCP, whereas sensitivity and specificity were 73% and 71% for using 25.0% or higher relative area less than 60 HU. The discriminatory ability of CTA for LCP was similar between the absolute and relative areas (the area under the curve, 0.744 versus 0.722; P = 0.37). Notably, the association of the low attenuation plaque area in CTA with LCP was not altered by the luminal enhancement for the relative (P = 0.48) but for the absolute measurement (P = 0.03). Similar results were achieved when validated against lipid-rich plaque by OCT in a subset of 285 cross sections. Conclusions: In ex vivo conditions, the relative area of coronary atherosclerotic plaque less than 60 HU in CTA as derived from quantitative histogram analysis has good accuracy to detect LCP as compared with a histological analysis independent of differences in luminal contrast enhancement. C1 [Schlett, Christopher L.; Maurovich-Horvat, Pal; Ferencik, Maros; Alkadhi, Hatem; Stolzmann, Paul; Scheffel, Hans; Seifarth, Harald; Do, Synho; Bamberg, Fabian; Hoffmann, Udo] Dept Radiol, Cardiac MR PET CT Program, Boston, MA USA. [Schlett, Christopher L.; Maurovich-Horvat, Pal; Ferencik, Maros; Alkadhi, Hatem; Stolzmann, Paul; Scheffel, Hans; Seifarth, Harald; Do, Synho; Bamberg, Fabian; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Schlett, Christopher L.; Kauczor, Hans-Ulrich] Heidelberg Univ, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Ferencik, Maros; Virmani, Renu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Nakano, Masataka; Vorpahl, Marc] CV Path Inst Inc, Gaithersburg, MD USA. [Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU GE Healthcare, Milwaukee, WI FX Supported by an unrestricted grant from GE Healthcare, Milwaukee, WI. NR 39 TC 13 Z9 14 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 EI 1536-0210 J9 INVEST RADIOL JI Invest. Radiol. PD SEP PY 2013 VL 48 IS 9 BP 646 EP 653 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 300EF UT WOS:000330446500003 PM 23614976 ER PT J AU Weir, GC Aguayo-Mazzucato, C Bonner-Weir, S AF Weir, Gordon C. Aguayo-Mazzucato, Cristina Bonner-Weir, Susan TI beta-cell dedifferentiation in diabetes is important, but what is it? SO ISLETS LA English DT Editorial Material DE beta cell; insulin secretion; diabetes; differentiation; dedifferentiation; islets ID INTENSIVE INSULIN THERAPY; PANCREATIC-ISLETS; CHRONIC HYPERGLYCEMIA; GLUCOSE; SECRETION; RELEASE; DYSFUNCTION; HETEROGENEITY; CULTURE; GENES C1 [Weir, Gordon C.; Aguayo-Mazzucato, Cristina; Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Res Div, Boston, MA 02115 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Res Div, Boston, MA 02115 USA. EM gordon.weir@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK066056, DK 93909, P30 DK036836, P30 DK36836, R01 DK 66056, R01 DK093909] NR 36 TC 22 Z9 22 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1938-2014 EI 1938-2022 J9 ISLETS JI Islets PD SEP-DEC PY 2013 VL 5 IS 5 BP 233 EP 237 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 299GN UT WOS:000330384200009 PM 24356710 ER PT J AU Chen, LX Mao, JJ Fernandes, S Galantino, ML Guo, WS LaRiccia, P Teal, VL Bowman, MA Schumacher, HR Farrar, JT AF Chen, Lan X. Mao, Jun J. Fernandes, Shawn Galantino, Mary Lou Guo, Wensheng LaRiccia, Patrick Teal, Valerie L. Bowman, Marjorie A. Schumacher, H. Ralph Farrar, John T. TI Integrating Acupuncture With Exercise-Based Physical Therapy for Knee Osteoarthritis A Randomized Controlled Trial SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE acupuncture; physical therapy; osteoarthritis of the knee; placebo-controlled randomized trial; obese patients; African American ID CHRONIC PAIN; ALTERNATIVE MEDICINE; CLINICAL IMPORTANCE; PATIENT; EXPECTATIONS; OUTCOMES; RECOMMENDATIONS; COMPLEMENTARY AB Background: Knee osteoarthritis is a chronic disease associated with significant morbidity and economic cost. The efficacy of acupuncture in addition to traditional physical therapy has received little study. Objective: The objective of this study was to compare the efficacy and safety of integrating a standardized true acupuncture protocol versus nonpenetrating acupuncture into exercise-based physical therapy (EPT). Methods: This was a randomized, double-blind, controlled trial at 3 physical therapy centers in Philadelphia, PA. We studied 214 patients (66% African Americans) with at least 6 months of chronic knee pain and x-ray-confirmed Kellgren scores of 2 or 3. Patients received 12 sessions of acupuncture directly following EPT over 6 to 12 weeks. Acupuncture was performed at the same 9 points dictated by the traditional Chinese "Bi" syndrome approach to knee pain, using either standard needles or Streitberger non-skin-puncturing needles. The primary outcome was the proportion of patients with at least a 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index score at 12 weeks. Results: Both treatment groups showed improvement from combined therapy with no difference between true (31.6%) and nonpenetrating acupuncture (30.3%) in Western Ontario and McMaster Universities Osteoarthritis Index response rate (P = 0.5) or report of minor adverse events. A multivariable logistic regression prediction model identified an association between a positive expectation of relief from acupuncture and reported improvement. No differences were noted by race, sex, or age. Conclusions: Puncturing acupuncture needles did not perform any better than nonpuncturing needles integrated with EPT. Whether EPT, acupuncture, or other factors accounted for any improvement noted in both groups could not be determined in this study. Expectation for relief was a predictor of reported benefit. C1 [Chen, Lan X.] Univ Penn, Penn Presbyterian Med Ctr, Philadelphia, PA 19104 USA. [Mao, Jun J.; Fernandes, Shawn; Galantino, Mary Lou; Guo, Wensheng; LaRiccia, Patrick; Teal, Valerie L.; Bowman, Marjorie A.; Farrar, John T.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Mao, Jun J.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Galantino, Mary Lou] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph] Richard Stockton Coll New Jersey, Program Phys Therapy, Galloway, NJ USA. [Schumacher, H. Ralph] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Farrar, JT (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Blockley Hall,Room 816,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jfarrar@mail.med.upenn.edu FU National Institutes of Health/National Center for Complementary and Alternative Medicine (NCCAM) [R01-AT000304]; NCCAM [K23 AT004112] FX This study is supported by a grant from the National Institutes of Health/National Center for Complementary and Alternative Medicine (NCCAM) R01-AT000304. Dr Mao is also supported by NCCAM K23 AT004112. The funding agency had no role in the design and conduct of this study. NR 37 TC 9 Z9 10 U1 0 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD SEP PY 2013 VL 19 IS 6 BP 308 EP 316 DI 10.1097/RHU.0b013e3182a21848 PG 9 WC Rheumatology SC Rheumatology GA 300KC UT WOS:000330461800002 PM 23965480 ER PT J AU Hawkins, EJ Malte, CA Grossbard, J Saxon, AJ Imel, ZE Kivlahan, DR AF Hawkins, Eric J. Malte, Carol A. Grossbard, Joel Saxon, Andrew J. Imel, Zac E. Kivlahan, Daniel R. TI Comparative Safety of Benzodiazepines and Opioids Among Veterans Affairs Patients With Posttraumatic Stress Disorder SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE Posttraumatic stress disorder; antidepressants; opioids; benzodiazepines; adverse events ID PRESCRIPTION OPIOIDS; MILITARY SERVICE; NONCANCER PAIN; METAANALYSIS; OVERDOSE; PTSD; MORTALITY; PATTERNS; TRENDS; FALLS AB Objectives: Although Veterans Affairs (VA) patients with posttraumatic stress disorder (PTSD) are prescribed benzodiazepines and opioids in addition to recommended pharmacotherapies, little is known about the safety of these medications. This study compared the 2-year incidence of adverse events among VA patients with PTSD exposed to combinations of selective serotonin reuptake inhibitors (SSRIs) or serotonin/norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, and opioids. Methods: This retrospective cohort study used VA administrative data from 2004 to 2010 to identify and follow 5236 VA patients with PTSD with new episodes of (1) SSRIs/SNRIs only; (2) concurrent SSRIs/SNRIs and benzodiazepines; and (3) concurrent SSRIs/SNRIs, benzodiazepines, and opioids. Outcome measures were the 2-year incidence and adjusted hazard ratios (AHR) of mental health and medicine/surgery hospitalizations, emergency department visits, harmful events (eg, injuries and death), and any adverse event after adjustment for demographics, clinical covariates, and adverse event history. Results: Comparedwith SSRIs/SNRIs only, the adjusted risk of mental health hospitalizations (AHR: 1.87; 95% confidence interval [CI]: 1.37-2.53) was greater among patients prescribed SSRIs/SNRIs and benzodiazepines concurrently. The AHR of mental health hospitalizations (AHR: 2.00; 95% CI: 1.35-2.98), medicine/surgery hospitalizations (AHR: 4.86; 95% CI: 3.30-7.14), emergency department visits (AHR: 2.01; 95% CI: 1.53-2.65), any harmful event (2.92; 95% CI: 2.21-3.84), and any adverse event (AHR: 2.65; 95% CI: 2.18-3.23) were all significantly greater among patients prescribed SSRIs/SNRIs, benzodiazepines, and opioids than among those prescribed SSRIs/SNRIs only. Conclusions: Concurrently prescribing SSRIs/SNRIs, benzodiazepines, and opioids among patients with PTSD is associated with adverse events. Although efforts are warranted to monitor patients who are prescribed combinations of these medications to prevent adverse events, these results should be interpreted with caution until they are replicated. C1 [Hawkins, Eric J.; Malte, Carol A.; Grossbard, Joel; Kivlahan, Daniel R.] Hlth Serv Res & Dev, Seattle, WA USA. [Hawkins, Eric J.; Malte, Carol A.; Saxon, Andrew J.; Kivlahan, Daniel R.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Hawkins, Eric J.; Saxon, Andrew J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Imel, Zac E.] Univ Utah, Dept Educ Psychol, Salt Lake City, UT 84112 USA. RP Hawkins, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Eric.Hawkins@va.gov OI imel, zachary/0000-0001-9645-7184 FU U.S. Department of Veterans Affairs, Veterans Health Administration; Center of Excellence in Substance Abuse Treatment and Education FX This material is based on the work supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, and Center of Excellence in Substance Abuse Treatment and Education. Supporting organizations had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. NR 34 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD SEP-OCT PY 2013 VL 7 IS 5 BP 354 EP 362 DI 10.1097/ADM.0b013e31829e3957 PG 9 WC Substance Abuse SC Substance Abuse GA 300KR UT WOS:000330463300008 PM 24091764 ER PT J AU Chan, ST Yuen, JWM Gohel, MDI Wong, HC Chung, CP Sun, Y Ng, JN Lie, R Kwong, KK AF Chan, Suk-tak Yuen, John W. M. Gohel, Mayur-Danny I. Wong, Ho-cheong Chung, Chi-ping Sun, Yu Ng, Jia-nian Lie, Rosalind Kwong, Kenneth K. TI Does Guasha Offer Hepatoprotective Effect to Chronic Inactive Hepatitis B Carriers? A Built-in Design to Control Subject Expectation SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEME OXYGENASE-1; SHA THERAPY; INFECTION AB Background: A previous case study showed that Guasha, an ancient manual therapeutic technique, could exert hepatoprotective effect in a human chronic active hepatitis B carrier (active-CHB) by modulating the liver enzymes, cytokines, and heme oxygenase-1 (HO-1). The present study serves as a control to the aforementioned case report. The controls were chronic inactive carriers (inactive-CHB) and noncarriers of hepatitis B (NCs). Besides showing a difference in biochemical markers between controls and the previously reported active-CHB case, the asymptomatic condition in both inactive-and active-CHB offers an excellent control for the patient's expectation about Guasha's efficacy. The purpose of this case study was to investigate whether hepatoprotective biochemical markers previously measured in active-CHB in response to Guasha were also present in controls. Participants and Methods: Four inactive-CHB and nine NC participants were included. Each participant received a 15-minute Guasha treatment. Blood samples were obtained immediately before Guasha (day 0) and after Guasha (days 2, 5, and 7). Biochemistry values for liver function, HO-1, and T-helper (Th) cytokines were determined from blood tests. Neither the participants nor the investigator who administered Guasha were aware of the blood test results until after all data were collected for all participants. Results: In both inactive-CHB and NC participants, liver function, serum HO-1, and Th1/Th2 cytokines did not significantly differ before and after Guasha. Conclusions: In contrast to results in active-CHB patients, Guasha did not induce any significant modulation of liver enzymes, HO-1, or cytokines in inactive-CHB and NC participants. The current results suggest that a Guasha-induced hepatoprotective effect depends on the inflammatory event or clinical stage of chronic hepatitis B. Because both active and inactive carriers were completely unaware of their liver status at the time of receiving Guasha, the research protocol is effective in discounting the model that attributes the Guasha therapeutic efficacy to a placebo effect due to participants' expectations. C1 [Chan, Suk-tak; Kwong, Kenneth K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Yuen, John W. M.] Hong Kong Polytech Univ, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. [Gohel, Mayur-Danny I.; Ng, Jia-nian; Lie, Rosalind] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China. [Wong, Ho-cheong] Hong Kong Polytech Univ, Univ Hlth Serv, Hong Kong, Hong Kong, Peoples R China. [Sun, Yu] Hokkaido Univ, Grad Sch Life Sci, Dept Mol Neuropathol, Sapporo, Hokkaido 060, Japan. RP Chan, ST (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM phoebe@nmr.mgh.harvard.edu RI Chan, Suk-tak/G-5846-2015; Yuen, John Wai-Man/A-4963-2011 OI Yuen, John Wai-Man/0000-0003-1681-233X FU Hong Kong Polytechnic University [5-ZD64] FX This research was supported by The Hong Kong Polytechnic University (5-ZD64). We thank the subjects for their participation in this study. NR 18 TC 1 Z9 1 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2013 VL 19 IS 9 BP 772 EP 776 DI 10.1089/acm.2012.0186 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 300IN UT WOS:000330457700007 PM 23577623 ER PT J AU Batchelor, TT AF Batchelor, Tracy T. TI Flying Solo: Chemotherapy Without Radiation for Primary CNS Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID NERVOUS-SYSTEM LYMPHOMA; WHOLE-BRAIN RADIOTHERAPY; HIGH-DOSE METHOTREXATE; RECURRENT PRIMARY CNS; COGNITIVE FUNCTIONS; TRIAL C1 [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Boston, MA USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. FU NCI NIH HHS [K24 CA125440] NR 18 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2013 VL 31 IS 25 BP 3051 EP + DI 10.1200/JCO.2013.48.9138 PG 4 WC Oncology SC Oncology GA 301OC UT WOS:000330540600003 PM 23715569 ER PT J AU Metzger, O Sun, ZX Viale, G Price, KN Crivellari, D Snyder, RD Gelber, RD Castiglione-Gertsch, M Coates, AS Goldhirsch, A Cardoso, F AF Metzger-Filho, Otto Sun, Zhuoxin Viale, Giuseppe Price, Karen N. Crivellari, Diana Snyder, Raymond D. Gelber, Richard D. Castiglione-Gertsch, Monica Coates, Alan S. Goldhirsch, Aron Cardoso, Fatima TI Patterns of Recurrence and Outcome According to Breast Cancer Subtypes in Lymph Node-Negative Disease: Results From International Breast Cancer Study Group Trials VIII and IX SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT CHEMOENDOCRINE THERAPY; POPULATION-BASED COHORT; 2 RANDOMIZED-TRIALS; MOLECULAR PORTRAITS; HORMONE-RECEPTOR; PREDICTIVE-VALUE; CNS METASTASES; SURVIVAL; EXPRESSION; RELAPSE AB Purpose To retrospectively evaluate the pattern of recurrence and outcome of node-negative breast cancer (BC) according to major subtypes. Patients and Methods In all, 1,951 patients with node-negative, early-stage BC randomly assigned in International Breast Cancer Study Group Trials VIII and IX with centrally reviewed pathology data were included. BC subtypes were defined as triple negative (TN; n = 310), human epidermal growth factor receptor 2 (HER2) positive (n = 369), and hormone receptor positive with high (luminal B-like [LB-like]; n = 763) or low (luminal A-like [LA-like]; n = 509) proliferative activity by Ki-67 labeling index. BC-free interval (BCFI) events were invasive BC recurrence in local, contralateral breast, nodal, bone, or visceral sites. Time to first site-specific recurrence was evaluated by using cumulative incidence and competing risks regression analysis. Results Median follow-up was 12.5 years. The 10-year BCFI was higher for patients with LA-like (86%) BC compared with LB-like (76%), HER2 (73%), and TN (71%; P < .001) BC. TN and HER2 cohorts had higher hazard of BCFI event in the first 4 years after diagnosis (pre-trastuzumab). LB-like cohorts had a continuously higher hazard of BCFI event over time compared with LA-like cohorts. Ten-year overall survival was higher for LA-like (89%) compared with LB-like (83%), HER2 (77%), and TN (75%; P < .001) BC. LB-like subtypes had higher rates of bone as first recurrence site than other subtypes (P = .005). Visceral recurrence as first site was lower for the LA-like subgroup, with similar incidence among the other subgroups when treated with chemotherapy (P = .003). Conclusion BC subtypes have different distant recurrence patterns over time. Defining different patterns of BC recurrence can improve BC care through surveillance guidelines and can guide the design of clinical studies. (C) 2013 by American Society of Clinical Oncology C1 [Metzger-Filho, Otto] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sun, Zhuoxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Viale, Giuseppe; Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Viale, Giuseppe] Univ Milan, Milan, Italy. [Crivellari, Diana] Ctr Riferimento Oncol, Aviano, Italy. [Snyder, Raymond D.] St Vincents Hosp, Melbourne, Vic, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Castiglione-Gertsch, Monica] Univ Hosp, Geneva, Switzerland. [Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Cardoso, Fatima] Champalimaud Canc Ctr, P-1400048 Lisbon, Portugal. RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Av Brasilia Doca Pedroucos, P-1400048 Lisbon, Portugal. EM fatimacardoso@fundacaochampalimaud.pt OI Cardoso, Fatima/0000-0002-6692-2249 FU Swiss Group for Clinical Cancer Research; Frontier Science and Technology Research Foundation; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council); National Institutes of Health [CA-75362]; Swedish Cancer Society; Cancer Association of South Africa; Foundation for Clinical Cancer Research of Eastern Switzerland FX Supported in part by the Swiss Group for Clinical Cancer Research, Frontier Science and Technology Research Foundation, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council), Grant No. CA-75362 from the National Institutes of Health, Swedish Cancer Society, Cancer Association of South Africa, and the Foundation for Clinical Cancer Research of Eastern Switzerland. NR 38 TC 68 Z9 71 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2013 VL 31 IS 25 BP 3083 EP + DI 10.1200/JCO.2012.46.1574 PG 9 WC Oncology SC Oncology GA 301OC UT WOS:000330540600009 PM 23897954 ER PT J AU Freidlin, B Sun, ZX Gray, R Korn, EL AF Freidlin, Boris Sun, Zhuoxin Gray, Robert Korn, Edward L. TI Phase III Clinical Trials That Integrate Treatment and Biomarker Evaluation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; DESIGNS; FLUOROURACIL; PANITUMUMAB; LEUCOVORIN; ERLOTINIB C1 [Freidlin, Boris; Korn, Edward L.] NCI, Bethesda, MD 20852 USA. [Sun, Zhuoxin; Gray, Robert] Eastern Cooperat Oncol Grp, Boston, MA USA. [Sun, Zhuoxin; Gray, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, EPN 8129, Bethesda, MD 20852 USA. EM freidlinb@ctep.nci.nih.gov FU National Institutes of Health [CA023318] FX Supported in part by Grant No. CA023318 from the National Institutes of Health. NR 16 TC 19 Z9 19 U1 1 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2013 VL 31 IS 25 BP 3158 EP 3161 DI 10.1200/JCO.2012.48.3826 PG 4 WC Oncology SC Oncology GA 301OC UT WOS:000330540600018 PM 23569306 ER PT J AU Haddad, R AF Haddad, Robert TI Larynx Preservation: A Debate Worth Preserving SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID NECK-CANCER; FLUOROURACIL; DOCETAXEL; CISPLATIN; HEAD C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Haddad, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2013 VL 31 IS 25 BP 3170 EP 3170 DI 10.1200/JCO.2013.49.1332 PG 1 WC Oncology SC Oncology GA 301OC UT WOS:000330540600025 PM 23897959 ER PT J AU Taneja, AK Bredella, MA Chang, CY Simeone, FJ Kattapuram, SV Torriani, M AF Taneja, Atul K. Bredella, Miriam A. Chang, Connie Y. Simeone, F. Joseph Kattapuram, Susan V. Torriani, Martin TI Extrinsic Wrist Ligaments: Prevalence of Injury by Magnetic Resonance Imaging and Association With Intrinsic Ligament Tears SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE wrist; extrinsic; intrinsic; trauma; ligaments; MR imaging ID DORSAL INTERCARPAL LIGAMENT; SCAPHOLUNATE INSTABILITY; RADIOCARPAL LIGAMENTS; SCAPHOID FRACTURES; MR ARTHROGRAPHY; NORMAL ANATOMY; CAPSULODESIS; ADULT; FETAL AB Objective: The objective of this study was to determine the prevalence of extrinsic wrist ligament injury by magnetic resonance imaging and its association with intrinsic ligament tears. Methods: We reviewed conventional magnetic resonance images performed over a 5-year period from adult patients in the setting of wrist trauma. Two musculoskeletal radiologists examined the integrity of wrist ligaments and presence of bone abnormalities. Results: In a cohort of 75 subjects, extrinsic ligament injury was present in 75%, with radiolunotriquetral being most frequently affected (45%). Intrinsic ligament injury was present in 60%. Almost half of subjects had combined intrinsic and extrinsic ligament injury. Bone abnormalities were seen in 69%. The rate of extrinsic injury was higher in subjects with bone injury (P = 0.008). Conclusions: There is high prevalence of extrinsic ligament injury in the setting of wrist trauma, especially in the presence of bone abnormalities, with combined injury of intrinsic and extrinsic ligaments in about half of cases. C1 Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM torriani.martin@mgh.harvard.edu RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 22 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2013 VL 37 IS 5 BP 783 EP 789 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 298TW UT WOS:000330348400023 PM 24045257 ER PT J AU Matthews, JD Siefert, CJ Blais, MA Park, LT Siefert, CJ Welch, CA DuBois, CM van Nieuwenhuizen, AO Rooney, KO Seabrook, RC Durham, LE Adams, HC Fava, M AF Matthews, John D. Siefert, Caleb J. Blais, Mark A. Park, Lawrence T. Siefert, Caleb J. Welch, Charles A. DuBois, Christina M. van Nieuwenhuizen, Adrienne O. Rooney, Kathryn O. Seabrook, Rita C. Durham, Lauren E. Adams, Heather C. Fava, Maurizio TI A Double-blind, Placebo-Controlled Study of the Impact of Galantamine on Anterograde Memory Impairment During Electroconvulsive Therapy SO JOURNAL OF ECT LA English DT Article DE galantamine; electroconvulsive therapy; anterograde memory impairment ID DIFFERENT STIMULUS INTENSITIES; RANDOMIZED CONTROLLED-TRIAL; RESISTANT MAJOR DEPRESSION; ACETYLCHOLINESTERASE INHIBITION; NEUROPSYCHOLOGICAL STATUS; REPEATABLE BATTERY; BRAIN LEVELS; ECT; EFFICACY; RECEPTORS AB Background: Electroconvulsive therapy (ECT) continues to be an effective treatment option for patients who fail to respond to pharmacological interventions, are unable to tolerate medications, and show a suboptimal response to behavioral and psychotherapeutic treatments. However, risks for cognitive impairment may contribute to some patients' refusal of ECT. Methods: The present study examined galantamine as a pharmacological intervention to reduce cognitive adverse effects from ECT. Thirty-nine inpatients diagnosed with major depressive disorder; bipolar disorder, depressed type; or schizoaffective disorder, depressed type and admitted for ECT were randomized to galantamine or placebo. Study drugs were initiated 24 to 48 hours before starting ECT and continued throughout the course of ECT. A neuropsychological test battery was administered at baseline and 24 to 48 hours after completing a course of ECT treatments. Depression severity was monitored using the 17-item Hamilton Rating Scale for Depression and Clinical Global Impression Scale at baseline, weekly, and end point. Self-rated adverse effects were monitored weekly. Results: Thirty participants (12 patients in the galantamine group, 18 patients in the placebo group) had both pretreatment and post-treatment neuropsychological ratings. Those in the galantamine group scored significantly higher at discharge for delayed memory (t(28) = 2.44, P < 0.05). Hierarchical regressions examined if treatment condition predicted changes in delayed memory scores from baseline to discharge. Inclusion of the treatment condition in the final model made a significant incremental improvement in prediction (Delta R-2 = 0.12, F-1,F-27 change = 4.65, P < 0.05; beta = 0.37, t = 2.16, P < 0.05). Galantamine was well tolerated with no clinically significant bradycardia or prolonged paralysis when administered with ECT. Conclusions: Galantamine may be protective against impairment in retention of new learning. Galantamine exhibited minimal adverse effects and was safe when administered during ECT. The present findings require replication by future researchers using larger samples before broad conclusions can be drawn. C1 [Matthews, John D.; Blais, Mark A.; Welch, Charles A.; DuBois, Christina M.; van Nieuwenhuizen, Adrienne O.; Rooney, Kathryn O.; Seabrook, Rita C.; Durham, Lauren E.; Adams, Heather C.; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Matthews, John D.; Park, Lawrence T.; Welch, Charles A.; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Siefert, Caleb J.] Univ Michigan, Dearborn, MI 48128 USA. [Park, Lawrence T.; Siefert, Caleb J.] US FDA, Silver Spring, MD USA. RP Matthews, JD (reprint author), 55 Fruit St,Blake 11, Boston, MA 02114 USA. EM jmatthews@partners.org FU Janssen Pharmaceutica FX This study was funded by Janssen Pharmaceutica. NR 70 TC 8 Z9 8 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 EI 1533-4112 J9 J ECT JI J. ECT PD SEP PY 2013 VL 29 IS 3 BP 170 EP 178 DI 10.1097/YCT.0b013e31828b3523 PG 9 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 298YX UT WOS:000330362100015 PM 23519225 ER PT J AU Pompili, M Sher, L Serafini, G Forte, A Innamorati, M Dominici, G Lester, D Amore, M Girardi, P AF Pompili, Maurizio Sher, Leo Serafini, Gianluca Forte, Alberto Innamorati, Marco Dominici, Giovanni Lester, David Amore, Mario Girardi, Paolo TI Posttraumatic Stress Disorder and Suicide Risk Among Veterans A Literature Review SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Review DE Suicidal behavior; PTSD; veterans; risk factors; prevention ID AFGHANISTAN WAR VETERANS; VIETNAM VETERANS; DEPRESSED-PATIENTS; PTSD; IDEATION; COMORBIDITY; MILITARY; IRAQ; EXPOSURE; BEHAVIOR AB Posttraumatic stress disorder (PTSD) is frequently associated with suicidal ideation and suicide attempts. Suicide is an important cause of death in veterans, and the risk for intentional death continues to be high many years after service. The aim of the present study was to investigate whether there is a relationship between PTSD and suicidal behavior among veterans. We also discussed the risk factors of suicide among war veterans with PTSD. A systematic review was conducted focusing on war-related PTSD and suicidal behavior. A total of 80 articles from peer-reviewed journals were identified, 34 were assessed for eligibility, and 16 were included. Having a history of PTSD is associated with higher rates of morbidity and mortality and increased the risk for suicidal behavior. The association between PTSD and suicidal behavior was confirmed by the presence of other risk factors and high rates of comorbidity. Current suicidal behavior should be adequately assessed in war veterans. C1 [Pompili, Maurizio; Serafini, Gianluca; Forte, Alberto; Innamorati, Marco; Dominici, Giovanni; Girardi, Paolo] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs, Suicide Prevent Ctr, St Andrea Hosp, I-00185 Rome, Italy. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. [Lester, David] Richard Stockton Coll New Jersey, Galloway, NJ USA. [Amore, Mario] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Sect Psychiat, Genoa, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, Dept Psychiat, St Andrea Hosp, 1035 Via Grottarossa, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it OI Pompili, Maurizio/0000-0003-1886-4977 FU Italian Ministry of University Research-PRIN Project FX This study was supported, in part, by a grant from the Italian Ministry of University Research-PRIN Project (M. P., G. S., P. G.). NR 54 TC 30 Z9 31 U1 6 U2 35 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 2013 VL 201 IS 9 BP 802 EP 812 DI 10.1097/NMD.0b013e3182a21458 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 299DM UT WOS:000330375300012 PM 23995037 ER PT J AU Weingart, SN Carbo, A Tess, A Chiappetta, L Tutkus, S Morway, L Toth, M Davis, RB Phillips, RS Bates, DW AF Weingart, Saul N. Carbo, Alexander Tess, Anjala Chiappetta, Laurel Tutkus, Sherri Morway, Laurinda Toth, Maria Davis, Roger B. Phillips, Russell S. Bates, David W. TI Using a Patient Internet Portal to Prevent Adverse Drug Events: A Randomized, Controlled Trial SO JOURNAL OF PATIENT SAFETY LA English DT Article DE adverse drug event; patient safety; Internet portal; patient-physician communication ID PERSONAL HEALTH RECORDS; PRIMARY-CARE AB Objectives: Adverse drug events (ADEs) are common in ambulatory care and may result from poor patient-physician communication about medication-related symptoms. A module was developed within an electronic patient portal that was designed to enhance communication about medication symptoms and, in turn, reduce ADEs and health-care utilization. Methods: The researchers conducted a randomized, controlled clinical trial of MedCheck, an automated electronic message generated in a patient Internet portal. MedCheck asked intervention patients if they had filled a recent prescription and if they had experienced any problems with the medication. Patients' responses were forwarded automatically to primary care physicians. The study enrolled 375 intervention patients and 363 controls. After 3 months, the investigators reviewed patients' medical records and conducted telephone interviews to identify ADEs and to assess health-care utilization. Results: Among the 375 intervention patients, 184 (49%) responded to at least 1 MedCheck message. Patients reported 52 unfilled prescriptions and 56 medication problems. Patients responded to 72% of messages within 1 day. There was no statistically significant difference between intervention and control groups in the rate of ADEs, preventable or ameliorable ADEs, serious ADEs, or in subjects' health-care utilization. Conclusions: Internet portals have the potential to enhance patient-physician communication. However, additional development is required to demonstrate that such interventions can improve medication safety or health-care utilization. C1 [Weingart, Saul N.; Chiappetta, Laurel; Morway, Laurinda] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. [Weingart, Saul N.; Carbo, Alexander; Tess, Anjala; Tutkus, Sherri; Toth, Maria; Davis, Roger B.; Phillips, Russell S.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Weingart, Saul N.; Carbo, Alexander; Tess, Anjala; Davis, Roger B.; Phillips, Russell S.; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Weingart, SN (reprint author), Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. EM sweingart@tuftsmedicalcenter.org FU U.S. Agency for Healthcare Research and Quality [K08 HS11644]; Blue Cross Blue Shield of Massachusetts FX This study was supported by a clinical scientist career development award from the U.S. Agency for Healthcare Research and Quality (K08 HS11644) and a grant from Blue Cross Blue Shield of Massachusetts. The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review, or approval of the manuscript. NR 14 TC 1 Z9 1 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1549-8417 EI 1549-8425 J9 J PATIENT SAF JI J. Patient Saf. PD SEP PY 2013 VL 9 IS 3 BP 169 EP 175 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 300FT UT WOS:000330450500010 PM 23965840 ER PT J AU Mejaddam, AY Cropano, CM Kalva, S Walker, TG Imam, AM Velmahos, GC de Moya, MA King, DR AF Mejaddam, Ali Y. Cropano, Catrina M. Kalva, Sanjeeva Walker, T. Gregory Imam, Ayesha M. Velmahos, George C. de Moya, Marc A. King, David R. TI Outcomes following "rescue" superselective angioembolization for gastrointestinal hemorrhage in hemodynamically unstable patients SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Gastrointestinal hemorrhage; angiography; embolization; ischemia ID BLEEDING DUODENAL-ULCER; MICROCOIL EMBOLIZATION; TRANSCATHETER EMBOLIZATION; ARTERIAL EMBOLIZATION; MANAGEMENT; SURGERY AB BACKGROUND: Therapeutic angioembolization is a relatively new "rescue treatment'' modality for gastrointestinal hemorrhage (GIH) for unstable patients who fail primary treatment approaches; however, the effectiveness of this treatment and the incidence of ischemic necrosis following embolization for acute GIH are poorly described. The purpose of this study was to evaluate the effectiveness and safety of "rescue'' transcatheter superselective angioembolization (SSAE) for the treatment of hemodynamically unstable patients with GIH. METHODS: A 10-year retrospective review of all hemodynamically unstable patients (systolic blood pressure < 90 mm Hg and ongoing transfusion requirement) who underwent "rescue'' SSAE for GIH after failed endoscopic management was performed. All patients with evidence of active contrast extravasation were included. Data were collected on demographics, comorbidities, clinical presentation, and type of intravascular angioembolic agent used. Outcomes included technical success (cessation of extravasation), clinical success (no rebleeding requiring intervention within 30 days), and incidence of ischemic complications. RESULTS: Ninety-eight patients underwent SSAE for GIH during the study period; 47 were excluded owing to lack of active contrast extravasation. Of the remaining 51 patients, 22 (43%) presented with a lower GIH and 29 (57%) with upper GIH. The majority underwent embolization with a permanent agent (71%), while the remaining patients received either a temporary agent (16%) or a combination (14%). The overall technical and clinical success rates were 98% and 71%, respectively. Of the 14 patients with technical success but clinical failure (rebleeding within 30 days) and the 1 patient with technical failure, 4 were managed successfully with reembolization, while 2 underwent successful endoscopic therapy, and 9 had surgical resections. Only one patient had an ischemic complication (small bowel necrosis) requiring resection. CONCLUSION: SSAE, with reembolization if necessary, is an effective rescue treatment modality for hemodynamically unstable patients with active GIH. Of the patients, 20% will fail SSAE and require additional intervention. Ischemic complications are extremely rare. (Copyright (C) 2013 by Lippincott Williams & Wilkins) C1 [Kalva, Sanjeeva; Walker, T. Gregory] Massachusetts Gen Hosp, Div Vasc Intervent Radiol, Boston, MA 02114 USA. [Mejaddam, Ali Y.; Cropano, Catrina M.; Imam, Ayesha M.; Velmahos, George C.; de Moya, Marc A.; King, David R.] Massachusetts Gen Hosp, Div Trauma Acute Care Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP King, DR (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 NR 25 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD SEP PY 2013 VL 75 IS 3 BP 398 EP 403 DI 10.1097/TA.0b013e31829a8b7a PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 300GZ UT WOS:000330453700007 PM 23928742 ER PT J AU Weinstein, MM AF Weinstein, Milena M. TI Urinary incontinence: still waiting for a champion SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID OVERACTIVE BLADDER; WOMEN C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Weinstein, MM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP PY 2013 VL 20 IS 9 BP 881 EP 882 DI 10.1097/gme.0b013e3182a25e4a PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300KS UT WOS:000330463400002 PM 23963308 ER PT J AU Joffe, H White, DP Crawford, SL McCurnin, KE Economou, N Connors, S Hall, JE AF Joffe, Hadine White, David P. Crawford, Sybil L. McCurnin, Kristin E. Economou, Nicole Connors, Stephanie Hall, Janet E. TI Adverse effects of induced hot flashes on objectively recorded and subjectively reported sleep: results of a gonadotropin-releasing hormone agonist experimental protocol SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Hot flashes; Vasomotor symptoms; Sleep; Quality of life; Depressive symptoms; Actigraphy ID BREAST-CANCER SURVIVORS; CORE BODY-TEMPERATURE; MIDDLE-AGED WOMEN; QUALITY-OF-LIFE; MENOPAUSAL TRANSITION; VASOMOTOR SYMPTOMS; PERIMENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; MASS-SPECTROMETRY; DEPRESSION SCALE AB Objective: The impact of hot flashes on sleep is of great clinical interest, but results are inconsistent, especially when both hot flashes and sleep are measured objectively. Using objective and subjective measurements, we examined the impact of hot flashes on sleep by inducing hot flashes with a gonadotropin-releasing hormone agonist. Methods: The gonadotropin-releasing hormone agonist leuprolide was administered to 20 healthy premenopausal volunteers without hot flashes or sleep disturbances. Induced hot flashes were assessed objectively (skin conductance monitor) and subjectively (daily diary) during 1-month follow-up. Changes from baseline in objective sleep quality (actigraphy) and subjective sleep quality (Pittsburgh Sleep Quality Index) were compared between women who developed and women who did not develop objective hot flashes and, in parallel analyses, subjective hot flashes. Results: New-onset hot flashes were recorded in 14 (70%) women and reported by 14 (70%) women (80% concordance). Estradiol was universally suppressed. Objective sleep efficiency worsened in women with objective hot flashes and improved in women without objective hot flashes (median decrease, 2.6%; median increase, 4.2%; P = 0.005). Subjective sleep quality worsened more in those with subjective hot flashes than in those without subjective hot flashes (median increase in Pittsburgh Sleep Quality Index, 2.5 vs 1.0; P = 0.03). Objective hot flashes were not associated with subjective sleep quality, nor were subjective symptoms linked to objective sleep measures. Conclusions: This experimental model of induced hot flashes demonstrates a causal relationship between hot flashes and poor sleep quality. Objective hot flashes result in worse objective sleep efficiency, whereas subjective hot flashes worsen perceived sleep quality. C1 [Joffe, Hadine; Economou, Nicole; Connors, Stephanie] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Dept Psychiat, Boston, MA 02114 USA. [White, David P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Internal Med,Div Sleep Med, Boston, MA 02115 USA. [Crawford, Sybil L.] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA USA. [McCurnin, Kristin E.; Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, Boston, MA USA. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Suite 2000,Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM hjoffe@partners.org OI Hall, Janet/0000-0003-4644-3061 FU Massachusetts General Hospital Claflin Distinguished Scholar Award; [5R01MH082922] FX This work was supported by grant 5R01MH082922 (H.J.) and by the Massachusetts General Hospital Claflin Distinguished Scholar Award ( H.J.). NR 62 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP PY 2013 VL 20 IS 9 BP 905 EP 914 DI 10.1097/gme.0b013e31828292d1 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300KS UT WOS:000330463400005 PM 23481119 ER PT J AU Abbatiello, SE Mani, DR Schilling, B MacLean, B Zimmerman, LJ Feng, XD Cusack, MP Sedransk, N Hall, SC Addona, T Allen, S Dodder, NG Ghosh, M Held, JM Hedrick, V Inerowicz, HD Jackson, A Keshishian, H Kim, JW Lyssand, JS Riley, CP Rudnick, P Sadowski, P Shaddox, K Smith, D Tomazela, D Wahlander, A Waldemarson, S Whitwell, CA You, J Zhang, SC Kinsinger, CR Mesri, M Rodriguez, H Borchers, CH Buck, C Fisher, SJ Gibson, BW Liebler, D MacCoss, M Neubert, TA Paulovich, A Regnier, F Skates, SJ Tempst, P Wang, M Carr, SA AF Abbatiello, Susan E. Mani, D. R. Schilling, Birgit MacLean, Brendan Zimmerman, Lisa J. Feng, Xingdong Cusack, Michael P. Sedransk, Nell Hall, Steven C. Addona, Terri Allen, Simon Dodder, Nathan G. Ghosh, Mousumi Held, Jason M. Hedrick, Victoria Inerowicz, H. Dorota Jackson, Angela Keshishian, Hasmik Kim, Jong Won Lyssand, John S. Riley, C. Paige Rudnick, Paul Sadowski, Pawel Shaddox, Kent Smith, Derek Tomazela, Daniela Wahlander, Asa Waldemarson, Sofia Whitwell, Corbin A. You, Jinsam Zhang, Shucha Kinsinger, Christopher R. Mesri, Mehdi Rodriguez, Henry Borchers, Christoph H. Buck, Charles Fisher, Susan J. Gibson, Bradford W. Liebler, Daniel MacCoss, Michael Neubert, Thomas A. Paulovich, Amanda Regnier, Fred Skates, Steven J. Tempst, Paul Wang, Mu Carr, Steven A. TI Design, Implementation and Multisite Evaluation of a System Suitability Protocol for the Quantitative Assessment of Instrument Performance in Liquid Chromatography-Multiple Reaction Monitoring-MS (LC-MRM-MS) SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TANDEM MASS-SPECTROMETRY; PEPTIDE IMMUNOAFFINITY ENRICHMENT; ABSOLUTE QUANTIFICATION; TARGETED PROTEOMICS; ISOTOPE-DILUTION; QUALITY-CONTROL; PROTEINS; PLASMA; LC/MS/MS; ASSAYS AB Multiple reaction monitoring (MRM) mass spectrometry coupled with stable isotope dilution (SID) and liquid chromatography (LC) is increasingly used in biological and clinical studies for precise and reproducible quantification of peptides and proteins in complex sample matrices. Robust LC-SID-MRM-MS-based assays that can be replicated across laboratories and ultimately in clinical laboratory settings require standardized protocols to demonstrate that the analysis platforms are performing adequately. We developed a system suitability protocol (SSP), which employs a predigested mixture of six proteins, to facilitate performance evaluation of LC-SID-MRM-MS instrument platforms, configured with nanoflow-LC systems interfaced to triple quadrupole mass spectrometers. The SSP was designed for use with low multiplex analyses as well as high multiplex approaches when software-driven scheduling of data acquisition is required. Performance was assessed by monitoring of a range of chromatographic and mass spectrometric metrics including peak width, chromatographic resolution, peak capacity, and the variability in peak area and analyte retention time (RT) stability. The SSP, which was evaluated in 11 laboratories on a total of 15 different instruments, enabled early diagnoses of LC and MS anomalies that indicated suboptimal LC-MRM-MS performance. The observed range in variation of each of the metrics scrutinized serves to define the criteria for optimized LCSID- MRM-MS platforms for routine use, with pass/ fail criteria for system suitability performance measures defined as peak area coefficient of variation < 0.15, peak width coefficient of variation < 0.15, standard deviation of RT < 0.15 min (9 s), and the RT drift < 0.5min (30 s). The deleterious effect of a marginally performing LC-SID-MRM-MS system on the limit of quantification (LOQ) in targeted quantitative assays illustrates the use and need for a SSP to establish robust and reliable system performance. Use of a SSP helps to ensure that analyte quantification measurements can be replicated with good precision within and across multiple laboratories and should facilitate more widespread use of MRM-MS technology by the basic biomedical and clinical laboratory research communities. C1 [Abbatiello, Susan E.; Mani, D. R.; Addona, Terri; Keshishian, Hasmik; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Schilling, Birgit; Cusack, Michael P.; Held, Jason M.; Gibson, Bradford W.] Buck Inst Res Aging, Novato, CA 94945 USA. [MacLean, Brendan; Tomazela, Daniela; MacCoss, Michael] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Zimmerman, Lisa J.; Shaddox, Kent; Whitwell, Corbin A.; Liebler, Daniel] Vanderbilt Univ, Nashville, TN 37232 USA. [Feng, Xingdong; Sedransk, Nell] Natl Inst Stat Sci, Res Triangle Pk, NC 27709 USA. [Hall, Steven C.; Allen, Simon; Fisher, Susan J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Dodder, Nathan G.; Rudnick, Paul] NIST, Gaithersburg, MD 20899 USA. [Ghosh, Mousumi; Tempst, Paul] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Hedrick, Victoria; Inerowicz, H. Dorota; Riley, C. Paige; Buck, Charles; Regnier, Fred] Purdue Univ, W Lafayette, IN 47907 USA. [Jackson, Angela; Smith, Derek; Borchers, Christoph H.] Univ Victoria, Genome BC Prote Ctr, Victoria, BC V8Z 7X8, Canada. [Kim, Jong Won; You, Jinsam; Wang, Mu] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Lyssand, John S.; Sadowski, Pawel; Wahlander, Asa; Waldemarson, Sofia; Neubert, Thomas A.] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY 10016 USA. [Lyssand, John S.; Sadowski, Pawel; Wahlander, Asa; Waldemarson, Sofia; Neubert, Thomas A.] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. [Zhang, Shucha; Paulovich, Amanda] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry] NCI, NIH, Bethesda, MD 20892 USA. [Skates, Steven J.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Abbatiello, SE (reprint author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM susana@broad.mit.edu RI Dodder, Nathan/C-7971-2015; OI Dodder, Nathan/0000-0001-5913-1767; Tempst, Paul/0000-0002-6680-3987; Held, Jason/0000-0001-8024-2736; Liebler, Daniel/0000-0002-7873-3031 FU National Cancer Institute [U24 CA126476, U24 126477, U24 126480, U24 CA126485, U24 126479]; National Institute of Standards and Technology [70NANB9H9001]; NCRR [S10 RR0021222]; National Institute of Statistical Sciences FX This work was supported by grants from the National Cancer Institute (U24 CA126476, U24 126477, U24 126480, U24 CA126485, and U24 126479), part of NCI Clinical Proteomic Technologies for Cancer (http://proteomics.cancer.gov) initiative. A component of this initiative is the Clinical Proteomic Technology Assessment for Cancer (CPTAC) Network and teams, which include the Broad Institute of MIT and Harvard (with the Fred Hutchinson Cancer Research Center, Massachusetts General Hospital, the University of North Carolina at Chapel Hill, the University of Victoria and the Plasma Proteome Institute), Memorial Sloan-Kettering Cancer Center (with the Skirball Institute at New York University), Purdue University (with Monarch Life Sciences, Indiana University, Indiana University-Purdue University Indianapolis and the Hoosier Oncology Group), University of California, San Francisco (with the Buck Institute for Age Research, Lawrence Berkeley National Laboratory, and the University of Texas M. D. Anderson Cancer Center), and Vanderbilt University School of Medicine (with the University of Texas M. D. Anderson Cancer Center, the University of Washington, and the University of Arizona). The UCSF CPTAC team gratefully acknowledges the support of the Canary Foundation for providing funds to purchase a 4000 QTRAP mass spectrometer. The Vanderbilt CPTAC team was additionally supported by Cooperative Agreement No. 70NANB9H9001 from the National Institute of Standards and Technology. BWG acknowledges instrumentation to the Buck Institute from an NCRR Shared Instrumentation grant S10 RR0021222. The NCI CPTAC also supported the work by the National Institute of Statistical Sciences. NR 35 TC 41 Z9 43 U1 0 U2 27 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2013 VL 12 IS 9 BP 2623 EP 2639 DI 10.1074/mcp.M112.027078 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 301MM UT WOS:000330536400019 PM 23689285 ER PT J AU Lu, P Roberts, CWM AF Lu, Ping Roberts, Charles W. M. TI The SWI/SNF tumor suppressor complex Regulation of promoter nucleosomes and beyond SO NUCLEUS-AUSTIN LA English DT Article DE nucleosome; chromatin remodeling; epigenetic instability; SWI/SNF; SNF5; BAF47; SMARCB1; Brg1; SMARCA4 ID RHABDOID TUMORS; GENE-EXPRESSION; CANCER; GENOME; TRANSCRIPTION; REGIONS; TUMORIGENESIS; ORGANIZATION; EPIGENETICS; ELONGATION AB Nucleosomes, octamers of histones wrapped in 147 bp of DNA, are the basic unit of chromatin. In eukaryotic cells, the placement of nucleosomes along the genome is highly organized, and modulation of this ordered arrangement contributes to regulation of gene expression. The SWI/SNF complex utilizes the energy of AT P hydrolysis to mobilize nucleosomes and remodel chromatin structure. Recently, the complex has also been implicated in oncogenesis as genes encoding multiple SWI/SNF subunits have been found mutated at high frequency across a wide spectrum of cancers. Given that epigenetic aberrations are now characterized as a hallmark of human cancer, hypotheses have been put forth that the SWI/SNF complex inhibits tumor formation by regulating key chromatin functions. To understand how the SWI/SNF complex contributes to nucleosome organization in vivo we performed a genome-wide study in mammalian cells. We found that inactivation of SWI/SNF subunits leads to disruptions of specific nucleosome patterning and a loss of nucleosome occupancy at a large number of promoters. These findings define a direct relationship between the SWI/SNF complex, chromatin structure and transcriptional regulation. In this extra view, we discuss our findings, their relevance to gene regulation and possible links to the tumor suppression activities of the SWI/SNF complex. C1 [Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu FU Alex's Lemonade Stand Innovation; Hyundai Hope on Wheels Awards (CWMR); Garrett B Smith Foundation; Miles for Mary; Cure AT/RT; Avalanna Fund (CWMR); [R01CA113794]; [R01CA172152] FX This work and our efforts described herein were supported in part by R01CA113794 and R01CA172152 (to CWMR) and Alex's Lemonade Stand Innovation and Hyundai Hope on Wheels Awards (CWMR). The Garrett B Smith Foundation, Miles for Mary, Cure AT/RT Now and the Avalanna Fund (CWMR) provided additional support. NR 48 TC 13 Z9 15 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1949-1034 EI 1949-1042 J9 NUCLEUS-AUSTIN JI Nucleus-Austin PD SEP-OCT PY 2013 VL 4 IS 5 BP 374 EP 378 DI 10.4161/nucl.26654 PG 5 WC Cell Biology SC Cell Biology GA 299HK UT WOS:000330386600010 PM 24145903 ER PT J AU Ecker, JL AF Ecker, Jeffrey L. TI Laboring Through Informed Consent SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID DELIVERY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Ecker, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. EM jecker@partners.org NR 5 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 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2013 VL 122 IS 3 BP 513 EP 514 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300DJ UT WOS:000330444300002 PM 23921877 ER PT J AU Rauh-Hain, JA del Carmen, MG AF Rauh-Hain, J. Alejandro del Carmen, Marcela G. TI Endometrial Stromal Sarcoma A Systematic Review SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID LYMPH-NODE METASTASES; UTERINE SARCOMAS; MESENCHYMAL TUMORS; BETA-CATENIN; UTERUS; GRADE; MANAGEMENT; NEOPLASMS; SURVIVAL; POPULATION AB OBJECTIVE: To summarize available studies with respect to evaluation and management of patients with endometrial stromal sarcoma and undifferentiated endometrial sarcoma. DATA SOURCES: We conducted an electronic search of research articles published in English between January 1, 1981, and January 1, 2013, using MEDLINE, PubMed, and ClinicalTrials.gov (www.clinicaltrials.gov) databases. METHODS OF STUDY SELECTION: Of the 115 studies initially identified, 86 were chosen after limiting the review to those articles focusing on endometrial stromal sarcoma and crossreferencing to eliminate duplication. Review articles were excluded. Of the 86 studies meeting eligibility criteria, 84 were retrospective, one was a prospective phase II trial, and one was a phase III randomized study. Data were extracted systematically. Each of the reviewers assessed the quality of each study independently. TABULATION, INTEGRATION, AND RESULTS: Data were abstracted using standard abstraction templates to summarize study findings. Given the rarity of this tumor, we report available data with respect to epidemiology, pathogenesis, prognostic factors, and treatment. Endometrial stromal sarcoma and undifferentiated endometrial sarcoma comprise an estimated 1% of all uterine cancers and less than 10% of all uterine mesenchymal neoplasms. Hysterectomy and bilateral salpingo-oophorectomy is the cornerstone of treatment for early-stage (I or II) disease. Surgical resection when feasible may also be appropriate for patients presenting with advanced-stage tumors. The value of adjuvant therapy for early-stage disease remains unproven. Hormone therapy continues to be the most efficacious treatment modality for patients with advanced-stage or recurrent disease. CONCLUSION: Endometrial stromal sarcoma and undifferentiated endometrial sarcoma are rare tumors. Surgical resection is appropriate for patients with early-stage (I or II) disease and those with resectable, advanced-stage (III or IV) tumors. Hormone therapy may be appropriate in treating advanced and recurrent disease. C1 [Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 39 TC 19 Z9 22 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 2013 VL 122 IS 3 BP 676 EP 683 DI 10.1097/AOG.0b013e3182a189ac PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300DJ UT WOS:000330444300025 PM 23921879 ER PT J AU Hollon, TC Price, RL Kwon, CH Chiocca, EA AF Hollon, Todd C. Price, Richard L. Kwon, Chang-Hyuk Chiocca, E. Antonio TI Mutations in glioblastoma oncosuppressive pathways pave the way for oncomodulatory activity of cytomegalovirus SO ONCOIMMUNOLOGY LA English DT Editorial Material DE viral oncology; tumor suppressor genes; brain tumor; glioma; rhabdomyosarcoma ID INFECTION AB Over the last decade, cytomegalovirus (CMV) has been suggested to promote the development of glioblastoma multiforme (GBM). recent evidence demonstrates that CMV contributes to the progression of GBM in the context of oncosuppressor gene mutations. This finding provides further insights into the mechanisms whereby CMV exacerbates the malignancy of GBM. C1 [Hollon, Todd C.] Univ Michigan Hlth Syst, Dept Neurosurg, Ann Arbor, MI USA. [Price, Richard L.; Kwon, Chang-Hyuk] Ohio State Univ, Wexner Med Ctr, Dardinger Neurooncol Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. [Kwon, Chang-Hyuk] Ohio State Univ, Wexner Med Ctr, James Comprehens Canc Ctr, Solid Tumor Program, Columbus, OH 43210 USA. [Chiocca, E. Antonio] Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvey Cushing Neurooncol Labs,Dept Neurol Surg, Boston, MA 02115 USA. [Chiocca, E. Antonio] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvey Cushing Neurooncol Labs,Dept Neurol Surg, Boston, MA 02115 USA. EM EAChiocca@partners.org NR 10 TC 5 Z9 5 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 EI 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PD SEP PY 2013 VL 2 IS 9 AR e25620 DI 10.4161/onci.25620 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 301EY UT WOS:000330516800016 ER PT J AU McNichol, L Lund, C Rosen, T Gray, M AF McNichol, Laurie Lund, Carolyn Rosen, Ted Gray, Mikel TI Medical Adhesives and Patient Safety: State of the Science Consensus Statements for the Assessment, Prevention, and Treatment of Adhesive-Related Skin Injuries SO ORTHOPAEDIC NURSING LA English DT Reprint ID TAPE; INFECTION; OUTBREAK; BACTERIA; ZYGOMYCOSIS AB Skin injury related to medical adhesive usage is a prevalent but underrecognized complication that occurs across all care settings and among all age groups. If proper technique for application and/or removal of adhesive products is not used, tissue trauma can occur, impacting patient safety and quality of life and increasing healthcare costs. Little guidance exists in the literature regarding appropriate selection and proper use of adhesive products to minimize medical adhesive-related skin injury, as well as best practices for skin care preventive strategies, application and removal techniques, and assessment and treatment of such injuries. In an effort to define best practices for prevention of such injury, a consensus panel of 23 recognized key opinion leaders convened to establish consensus statements on the assessment, prevention, and treatment of medical adhesive-related skin injury. The consensus summit was held in December 2012 and was made possible by an unrestricted educational grant from 3M. This document details the consensus definitions and statements and identifies research priorities for development of new adhesive technologies and protocols for skin protection. KEY WORDS: Bandages, Dressings, Medical adhesive, Skin integrity, Skin stripping, Skin tear, Surgical tape C1 [McNichol, Laurie] Cone Hlth Syst, Greensboro, NC USA. [Lund, Carolyn] Childrens Hosp, Oakland, CA 94609 USA. [Lund, Carolyn] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Rosen, Ted] Baylor Coll Med, Houston, TX 77030 USA. [Rosen, Ted] Houston Vet Affairs Med Ctr, Houston, TX USA. [Gray, Mikel] Univ Virginia, Charlottesville, VA 22908 USA. RP Gray, M (reprint author), Univ Virginia, Dept Urol, POB 800422, Charlottesville, VA 22908 USA. EM MG5K@hscmail.mcc.virginia.edu NR 79 TC 2 Z9 2 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0744-6020 EI 1538-8654 J9 ORTHOP NURS JI Orthop. Nurs. PD SEP-OCT PY 2013 VL 32 IS 5 BP 267 EP 281 DI 10.1097/NOR.0b013e3182a39caf PG 15 WC Nursing; Orthopedics SC Nursing; Orthopedics GA 298VA UT WOS:000330351400007 PM 24022422 ER PT J AU Viana, LM Seyyedi, M Brewer, CC Zalewski, C DiGiovanna, JJ Tamura, D Totonchy, M Kraemer, KH Nadol, JB AF Viana, Lucas M. Seyyedi, Mohammad Brewer, Carmen C. Zalewski, Christopher DiGiovanna, John J. Tamura, Deborah Totonchy, Mariam Kraemer, Kenneth H. Nadol, Joseph B., Jr. TI Histopathology of the Inner Ear in Patients With Xeroderma Pigmentosum and Neurologic Degeneration SO OTOLOGY & NEUROTOLOGY LA English DT Article DE DNA repair; Sensorineural hearing loss; Temporal bone histopathology; Xeroderma pigmentosum ID DNA-REPAIR; COCKAYNE-SYNDROME; SUN SENSITIVITY; DEAFNESS; DISEASE; ABNORMALITIES AB Introduction: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations resulting in defective repair of DNA damage. XP patients have a markedly increased risk of ultraviolet-induced neoplasms and premature aging of sun-exposed tissue. Approximately 25% of XP patients in the United States have neurologic abnormalities including progressive sensorineural hearing loss (SNHL). Objective: To describe the temporal bone histopathology in 2 individuals with XP (XPA and XPD) with neurologic degeneration and to discuss the possible causes of deafness in these patients. Methods: Temporal bones were removed at autopsy and studied using light microscopy. Results: In the case with XPD, the organ of Corti was missing throughout the cochlea, whereas the case with XPA demonstrated scattered presence of sensory cells in the middle and apical turns. In both cases, there was moderate-to-severe patchy atrophy of the stria vascularis in all turns, and cochlear neurons were severely atrophied compared with age-matched controls, with loss of both peripheral dendrites and central axons. There was severe degeneration of Scarpa's ganglion in the case with XPA. Conclusion: Two cases of XP with neurologic degeneration are reported. The case with XPD demonstrated a more severe audiologic phenotype than XPA, although both had similar findings such as atrophy of the organ of Corti, stria vascularis, and spiral ganglia leading to severe or profound SNHL by the third decade of life. It is not clear if the neuronal degeneration in the inner ear was primary or secondary to loss of neuroepithelial cells. C1 [Viana, Lucas M.; Seyyedi, Mohammad; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Viana, Lucas M.; Seyyedi, Mohammad; Nadol, Joseph B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Viana, Lucas M.] Univ Brasilia, Fac Hlth Sci, BR-70910900 Brasilia, DF, Brazil. [Brewer, Carmen C.; Zalewski, Christopher] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Bethesda, MD USA. [DiGiovanna, John J.; Tamura, Deborah; Totonchy, Mariam; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Totonchy, Mariam] NIH, Clin Res Training Program, Bethesda, MD 20892 USA. RP Viana, LM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 4th Floor,243 Charles St, Boston, MA 02114 USA. EM lucasmvianaorl@gmail.com FU Center for Cancer Research, National Cancer Institute; National Institute on Deafness and Other Communication Disorders (NIDCD); Clinical Research Training Program; National Institutes of Health; Pfizer Inc; NIDCD [5U24DC011968] FX This research was supported by the Intramural Research Programs of the Center for Cancer Research, National Cancer Institute (D. T., J. J. D., M. T., and K. H. K.), the National Institute on Deafness and Other Communication Disorders (NIDCD) (C. Z. and C. C. B.), the Clinical Research Training Program (M. B. T.), a public-private partnership supported jointly by the National Institutes of Health and Pfizer Inc (via a grant to the Foundation for National Institutes of Health from Pfizer Inc.), and NIDCD grant no. 5U24DC011968 (J. B. N). NR 22 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2013 VL 34 IS 7 BP 1230 EP 1236 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 301HI UT WOS:000330523000023 PM 23928520 ER PT J AU Quesnel, AM Moonis, G Appel, J O'Malley, JT Curtin, HD McKenna, MJ AF Quesnel, Alicia M. Moonis, Gul Appel, Jason O'Malley, Jennifer T. Curtin, Hugh D. McKenna, Michael J. TI RESPONSE TO LETTER TO THE EDITOR BY DR. TAMAS KAROSI RE: "CORRELATION OF COMPUTED TOMOGRAPHY WITH HISTOPATHOLOGY IN OTOSLCEROSIS", QUESNEL ET AL. OTOL NEUROTOL 2013; 34(1):22-28 SO OTOLOGY & NEUROTOLOGY LA English DT Letter ID SENSORINEURAL HEARING-LOSS; OTOSCLEROSIS C1 [Quesnel, Alicia M.; O'Malley, Jennifer T.; McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Quesnel, Alicia M.; O'Malley, Jennifer T.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Moonis, Gul; Appel, Jason; Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Moonis, Gul] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Quesnel, AM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [U24 DC011943] NR 12 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD SEP PY 2013 VL 34 IS 7 BP 1363 EP 1364 PG 3 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 301HI UT WOS:000330523000045 PM 23921922 ER PT J AU Sarraf, D Chan, C Rahimy, E Abraham, P AF Sarraf, David Chan, Clement Rahimy, Ehsan Abraham, Prema TI PROSPECTIVE EVALUATION OF THE INCIDENCE AND RISK FACTORS FOR THE DEVELOPMENT OF RPE TEARS AFTER HIGH- AND LOW-DOSE RANIBIZUMAB THERAPY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE age-related macular degeneration; antivascular endothelial growth factor; ranibizumab; retinal pigment epithelial tears; vascularized pigment epithelial detachment ID PIGMENT EPITHELIAL TEAR; INTRAVITREAL BEVACIZUMAB INJECTION; OPTICAL COHERENCE TOMOGRAPHY; CHOROIDAL NEOVASCULARIZATION SECONDARY; PROLIFERATIVE DIABETIC-RETINOPATHY; MACULAR DEGENERATION; CLINICOPATHOLOGICAL CORRELATION; RETINAL-DETACHMENT; AVASTIN; PATHOGENESIS AB Purpose: To prospectively determine the incidence and risk factors for retinal pigment epithelial (RPE) tears in eyes with vascularized pigment epithelial detachments (PED) and exudative age-related macular degeneration receiving antivascular endothelial growth factor therapy. Methods: Eyes were prospectively randomized into 1 of 4 arms: 1) 0.5 mg of ranibizumab monthly for 12 months; 2) 0.5 mg of ranibizumab monthly for 3 months and then pro re nata on the basis of clinical and optical coherence tomography-guided indications; 3) high-dose 2.0 mg of ranibizumab monthly for 12 months; or 4) 2.0 mg of ranibizumab monthly for 3 months and then pro re nata thereafter. All PEDs were measured for height, greatest linear diameter, and surface area at baseline. The incidence of RPE tears in the entire 4-arm cohort was determined at the end of 12 months. Eyes were divided into two groups (tear vs. nontear) and statistically compared to determine risk factors for the development of RPE tear. Results: Of 37 eyes, a total of 5 developed postranibizumab RPE tears during the course of the study (incidence 14%). Four of the 5 tears occurred in the high-dose 2.0-mg groups. Baseline PED height, surface area, and greatest linear diameter were significantly greater in the group that developed RPE tears versus the nontear group (P = 0.018, 0.031, and 0.048, respectively). There were significantly more eyes with PED height >550 microns in the RPE tear group (4 of 5, 80%) compared with the nontear group (9 of 32, 18%) (P = 0.042). The presence of PED height >550 microns was associated with an increased tear rate from 14% to 31%. Furthermore, retrospective identification of a ring sign or Grade 1 tear at baseline, in addition to PED height >550 microns, was associated with a further increase in the tear rate to 67%. Conclusion: In this study, the prospective incidence of RPE tears was similar to 14%. A baseline PED height >550 microns and presence of a Grade 1 tear, or positive ring sign, were identified as high-risk factors for the subsequent development of an RPE tear. C1 [Sarraf, David; Rahimy, Ehsan] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Chan, Clement] Southern Calif Desert Retina Consultants, Med Grp, Palm Desert, CA USA. [Chan, Clement] Loma Linda Univ, Dept Ophthalmol, Loma Linda, CA 92350 USA. [Abraham, Prema] Black Hills Reg Eye Inst, Rapid City, SD 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 Genentech; Karl Kirchgessner Foundation at the Jules Stein Eye Institute FX Supported by an Investigator-Supported Trial grant from Genentech and by a grant (D. S.) from the Karl Kirchgessner Foundation at the Jules Stein Eye Institute. NR 51 TC 18 Z9 18 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2013 VL 33 IS 8 BP 1551 EP 1557 PG 7 WC Ophthalmology SC Ophthalmology GA 297CP UT WOS:000330233200009 PM 23652578 ER PT J AU Keck, KM Kalpathy-Cramer, J Ataer-Cansizoglu, E You, S Erdogmus, D Chiang, MF AF Keck, Katie M. Kalpathy-Cramer, Jayashree Ataer-Cansizoglu, Esra You, Sheng Erdogmus, Deniz Chiang, Michael F. TI PLUS DISEASE DIAGNOSIS IN RETINOPATHY OF PREMATURITY Vascular Tortuosity as a Function of Distance from Optic Disk SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE medical informatics; pediatric ophthalmology; retina; retinopathy of prematurity ID DIGITAL IMAGE-ANALYSIS; INTERNATIONAL CLASSIFICATION; RETINAL IMAGES; ACCURACY; TELEMEDICINE; AGREEMENT; SEGMENTATION; RELIABILITY; VESSELS; ROPTOOL AB Purpose: To examine vascular tortuosity as a function of distance from the optic disk in infants with retinopathy of prematurity. Methods: Thirty-four wide-angle retinal images from infants with retinopathy of prematurity were reviewed by 22 experts. A reference standard for each image was defined as the diagnosis (plus vs. not plus) given by the majority of experts. Tortuosity, defined as vessel length divided by straight line distance between vessel end points, was calculated as a function of distance from the disk margin for arteries and veins using computer-based methods developed by the authors. Results: Mean cumulative tortuosity increased with distance from the disk margin, both in 13 images with plus disease (P = 0.007 for arterial tortuosity [n = 62 arteries], P < 0.001 for venous tortuosity [n = 58 veins] based on slope of best fit line by regression), and in 21 images without plus disease (P < 0.001 for arterial tortuosity [n = 94 arteries], P < 0.001 for venous tortuosity [n = 85 veins]). Images with plus disease had significantly higher vascular tortuosity than images without plus disease (P < 0.05), up to 7.0 disk diameters from the optic disk margin. Conclusion: Vascular tortuosity was higher peripherally than centrally, both in images with and without plus disease, suggesting that peripheral retinal features may be relevant for retinopathy of prematurity diagnosis. C1 [Keck, Katie M.; Chiang, Michael F.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA. [Ataer-Cansizoglu, Esra; You, Sheng; Erdogmus, Deniz] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Chiang, Michael F.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Chiang, MF (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM chiangm@ohsu.edu OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU National Institutes of Health, Bethesda, MD [EY19474]; Research to Prevent Blindness, New York, NY; National Library of Medicine, Bethesda, MD [4R00LM009889] FX M.F. Chiang is supported by grant EY19474 from the National Institutes of Health, Bethesda, MD. K. M. Keck and M. F. Chiang are supported by unrestricted departmental funding from Research to Prevent Blindness, New York, NY. J. Kalpathy-Cramer is supported by grant 4R00LM009889 from the National Library of Medicine, Bethesda, MD. NR 37 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2013 VL 33 IS 8 BP 1700 EP 1707 PG 8 WC Ophthalmology SC Ophthalmology GA 297CP UT WOS:000330233200026 PM 23538582 ER PT J AU Dion, GR Weitzel, EK McMains, KC AF Dion, Gregory Robert Weitzel, Erik K. McMains, Kevin C. TI Current Approaches to Diagnosis and Management of Rhinitis SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE allergic rhinitis; infectious rhinitis; nasal airway obstruction; nonallergic rhinitis; nonallergic rhinitis with eosinophilia syndrome; rhinitis; vasomotor rhinitis ID AZELASTINE NASAL SPRAY; ALLERGIC RHINITIS; NONALLERGIC RHINITIS; SUBLINGUAL IMMUNOTHERAPY; GUSTATORY RHINITIS; ATOPIC MARCH; ASTHMA; MEDICAMENTOSA; SWIMMERS; EFFICACY AB Rhinitis affects >20% of the population and is a common reason patients visit their primary care physician. Proper therapeutic intervention initially requires differentiating rhinitis from acute and chronic rhinosinusitis. After establishing rhinitis as the etiology of a patient's symptoms, a careful, thoughtful history and physical examination aids the cause. Rhinitis can be allergic, nonallergic, or mixed (having features of both allergic and nonallergic rhinitis). Therapeutic interventions vary, depending on the etiology of rhinitis. Symptoms that are refractory to avoidance and pharmacotherapy warrant referral to an allergist or otolaryngologist for consideration of immunotherapy or surgical intervention. In many cases, adhering to an evidence-based therapeutic treatment algorithm will allow physicians to effectively manage rhinitis. C1 San Antonio Mil Med Ctr, Ft Sam Houston, TX USA. Wilford Hall Ambulatory Surg Ctr, San Antonio, TX USA. Audie L Murphy Vet Hosp, San Antonio, TX USA. RP Dion, GR (reprint author), ATTN MCHE SDT Oto, Dept Otolaryngol, 3551 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM greg.r.dion@us.army.mil OI Weitzel, Erik/0000-0001-9155-3556 NR 56 TC 1 Z9 1 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD SEP PY 2013 VL 106 IS 9 BP 526 EP 531 DI 10.1097/SMJ.0b013e3182a5f0f6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 298UE UT WOS:000330349200010 PM 24002559 ER PT J AU Deyo, RA Hickam, D Duckart, JP Piedra, M AF Deyo, Richard A. Hickam, David Duckart, Jonathan P. Piedra, Mark TI Complications After Surgery for Lumbar Stenosis in a Veteran Population SO SPINE LA English DT Article DE spinal stenosis; lumbar stenosis; lumbar fusion; complications; surgical complications; postoperative mortality; prediction rule; patient safety; risk prediction; receiver operating characteristic (ROC) ID SPINE SURGERY; RISK-FACTORS; WOUND INFECTIONS; FUSION SURGERY; INSTRUMENTATION; RATES AB Study Design. Secondary analysis of the prospectively collected Veterans Affairs National Surgical Quality Improvement Program database. Objective. Determine rates of major medical complications, wound complications, and mortality among patients undergoing surgery for lumbar stenosis and examine risk factors for these complications. Summary of Background Data. Surgery for spinal stenosis is concentrated among older adults, in whom complications are more frequent than among middle-aged patients. Many studies have focused on infections or device complications, but fewer studies have focused on major cardiopulmonary complications, using prospectively collected data. Methods. We identified patients who underwent surgery for a primary diagnosis of lumbar stenosis between 1998 and 2009 from the Veterans Affairs National Surgical Quality Improvement Program database. We created a composite of major medical complications, including acute myocardial infarction, stroke, pulmonary embolism, pneumonia, systemic sepsis, coma, and cardiac arrest. Results. Among 12,154 eligible patients, major medical complications occurred in 2.1%, wound complications in 3.2%, and 90-day mortality in 0.6%. Major medical complications, but not wound complications, were strongly associated with age. American Society of Anesthesiologists (ASA) class was a strong predictor of compli-cations. Insulin use, long-term corticosteroid use, and preoperative functional status were also significant predictors. Fusion procedures were associated with higher complication rates than with decompression alone. In logistic regressions, ASA class and age were the strongest predictors of major medical complications (odds ratio for ASA class 4 vs. class 1 or 2: 2.97; 95% confidence interval, 1.68-5.25; P = 0.0002). After adjustment for comorbidity, age, and functional status, fusion procedures remained associated with higher medical complication rates than were decompressions alone (odds ratio = 2.85; 95% confidence interval, 2.14-3.78; P < 0.0001). Conclusion. ASA class, age, type of surgery, insulin or corticosteroid use, and functional status were independent risk factors for major medical complications. These factors may help in selecting patients and planning procedures, improving patient safety. C1 [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97239 USA. [Deyo, Richard A.; Hickam, David] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Publ Hlth, Portland, OR 97239 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Prevent Med, Portland, OR 97239 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA. [Piedra, Mark] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. [Hickam, David; Duckart, Jonathan P.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, Dept Family Med, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Institute for Arthritis, Musculoskeletal and Skin Diseases [R01 AR054912]; National Center for Research Resources grant [UL1 RR024140]; Research Enhancement Award Program of the Veterans Health Administration FX National Institute for Arthritis, Musculoskeletal and Skin Diseases (R01 AR054912), National Center for Research Resources grant funds (UL1 RR024140), and the Research Enhancement Award Program of the Veterans Health Administration funds were received to support this work. This material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center, Portland, OR. NR 18 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD SEP 1 PY 2013 VL 38 IS 19 BP 1695 EP 1702 DI 10.1097/BRS.0b013e31829f65c1 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 299AN UT WOS:000330366800020 PM 23778366 ER PT J AU Hart, R McCarthy, I O'Brien, M Bess, S Line, B Adjei, OB Burton, D Gupta, M Ames, C Deviren, V Kebaish, K Shaffrey, C Wood, K Hostin, R AF Hart, Robert McCarthy, Ian O'Brien, Michael Bess, Shay Line, Brett Adjei, Oheneba Boachie Burton, Doug Gupta, Munish Ames, Christopher Deviren, Vedat Kebaish, Khaled Shaffrey, Christopher Wood, Kirkham Hostin, Richard CA Int Spine Study Grp TI Identification of Decision Criteria for Revision Surgery Among Patients With Proximal Junctional Failure After Surgical Treatment of Spinal Deformity SO SPINE LA English DT Article DE adult spinal deformity; revision surgery; proximal junctional failure ID PEDICLE SCREW CONSTRUCTS; RISK-FACTOR ANALYSIS; FOLLOW-UP; IDIOPATHIC SCOLIOSIS; KYPHOSIS; FUSION; OUTCOMES; INSTRUMENTATION; PARAMETERS AB Study Design. Multicenter, retrospective, consecutive case series. Objective. This study aims to identify demographic and radiographical characteristics that influence the decision to perform revision surgery among patients with proximal junctional failure (PJF). Summary of Background Data. Revision rates after PJF remain relatively high, yet the decision criteria for performing revision surgical procedures are not uniform and vary by surgeon. A better understanding of the factors that impact the decision to perform revision surgery is important in order to improve efficiency of surgical treatment of adult spinal deformity. Methods. A cohort of 57 patients with PJF was identified retrospectively from 1218 consecutive patients with adult spinal deformity. PJF was identified on the basis of 10 postoperative increase in kyphosis between upper instrumented vertebra (UIV) and UIV + 2, along with 1 or more of the following: fracture of the vertebral body of UIV or UIV + 1, posterior osseoligamentous disruption, or pullout of instrumentation at the UIV. Univariate statistical analysis was performed using t tests and Fisher exact tests. Multivariate analysis was performed using logistic regression. Results. Twenty-seven (47.4%) patients underwent revision surgery within 6 months of the index operation. Regression results revealed that patients with combined posterior/anterior approaches at index were significantly more likely to undergo revision (P = 0.001) as were patients with more extreme proximal junctional kyphosis angulation (P = 0.034). Patients sustaining trauma were also significantly more likely to undergo revision (P = 0.019). Variables approaching but not reaching significance as predictors of revision included female sex (P = 0.066) and higher sagittal vertical axis (SVA) (P = 0.090). Conclusion. The decision to perform revision surgery is complicated and varies by surgeon. Factors that seem to influence this decision include traumatic etiology of PJF, severity of proximal junctional kyphosis angulation, higher SVA, and female sex. Factors that were expected to influence revision but had no statistical effect included soft tissue versus bony mode of failure, age, levels C1 [Hart, Robert] Oregon Hlth & Sci Univ, Portland, OR USA. [McCarthy, Ian] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. [McCarthy, Ian] So Methodist Univ, Dallas, TX 75275 USA. [McCarthy, Ian; O'Brien, Michael; Hostin, Richard] Baylor Scoliosis Ctr, Plano, TX 75093 USA. [Bess, Shay; Line, Brett] Rocky Mt Scoliosis & Spine, Denver, CO USA. [Adjei, Oheneba Boachie] Hosp Special Surg, Dept Orthoped Surg, New York, NY 10021 USA. [Burton, Doug] Univ Kansas, Med Ctr, Dept Orthoped Surg, Kansas City, KS 66103 USA. [Gupta, Munish] Univ Calif Davis, Dept Orthoped Surg, Sacramento, CA 95817 USA. [Ames, Christopher] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Deviren, Vedat] Univ Calif San Francisco, Dept Orthoped Surg, San Francisco, CA 94143 USA. [Kebaish, Khaled] Johns Hopkins Univ, Dept Orthoped Surg, Baltimore, MD USA. [Shaffrey, Christopher] Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA. [Wood, Kirkham] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McCarthy, I (reprint author), Baylor Scoliosis Ctr, 4708 Alliance Blvd,Ste 800, Plano, TX 75093 USA. EM ianmccarthy.econ@gmail.com OI bess, shay/0000-0002-9697-8999 FU Baylor Health Care System Foundation; Seeger Endowment Fund; Children's Specialist Foundation, Inc. FX Funding in support of this work was provided in-part by the Baylor Health Care System Foundation, Seeger Endowment Fund, and the Children's Specialist Foundation, Inc. as administrator for the International Spine Study Group. NR 17 TC 15 Z9 17 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD SEP 1 PY 2013 VL 38 IS 19 BP E1223 EP E1227 DI 10.1097/BRS.0b013e31829fedde PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 299AN UT WOS:000330366800007 PM 23778370 ER PT J AU Feener, EP Zhou, QF Fickweiler, W AF Feener, Edward P. Zhou, Qunfang Fickweiler, Ward TI Role of plasma kallikrein in diabetes and metabolism SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Plasma kallikrein; diabetes; Klkb1; contact activation pathway ID PLATELET-DERIVED MICROPARTICLES; GLUCAGON-LIKE PEPTIDE-1; RETINAL VASCULAR DYSFUNCTION; GENOME-WIDE ASSOCIATION; GLYCATION END-PRODUCTS; FACTOR-XII; IN-VIVO; KININ SYSTEM; ADIPOCYTE DIFFERENTIATION; PREKALLIKREIN DEFICIENCY AB Plasma kallikrein (PK) is a serine protease generated from plasma pre-kallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition C1 [Feener, Edward P.; Zhou, Qunfang; Fickweiler, Ward] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Div Res, Boston, MA 02115 USA. RP Feener, EP (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU US National Institutes of Health [EY019029, NS077006, DK36836]; JDRF [17-2011-251] FX This work was supported in part by the US National Institutes of Health (grants EY019029, NS077006, & DK36836) and JDRF grant 17-2011-251. NR 90 TC 13 Z9 14 U1 0 U2 6 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP PY 2013 VL 110 IS 3 BP 434 EP 441 DI 10.1160/TH13-02-0179 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 297QW UT WOS:000330271000007 PM 23676986 ER PT J AU Dick, AAS Mercer, LD Smith, JM McDonald, RA Young, B Healey, PJ AF Dick, Andre A. S. Mercer, Laina D. Smith, Jodi M. McDonald, Ruth A. Young, Bessie Healey, Patrick J. TI Donor and Recipient Size Mismatch in Adolescents Undergoing Living-Donor Renal Transplantation Affect Long-Term Graft Survival SO TRANSPLANTATION LA English DT Article DE Body surface area; Renal transplantation; Pediatrics and living donor; Size mismatch; Graft survival ID KIDNEY-TRANSPLANTATION; RACIAL-DIFFERENCES; UNITED-STATES; DISPARITIES; GENDER; OUTCOMES; OVERUSE; FAILURE; WEIGHT; ACCESS AB Background. Controversies exist in the adult literature regarding the use of kidneys from small donors into larger recipients. Little is known regarding this issue in pediatric kidney transplantation. To assess the impact of donor/recipient size mismatch on long-term renal graft survival in pediatric patients undergoing living-donor renal transplantation. Methods. We reviewed the United Network for Organ Sharing database from 1987 to 2010 for adolescent (11-18 years old) patients who underwent primary living-donor renal transplantation. According to donor/recipient body surface area (BSA) ratio, patients were stratified into two categories: BSA ratio <0.9 and >= 0.9. Graft survival rates were compared between these two groups using Kaplan-Meier survival curves and Cox proportional hazards models. Results. Of the 1880 patients identified, 116 (6.2%) had a donor/recipient BSA ratio <0.9 and 1764 (93.8%) had a donor/recipient BSA ratio >= 0.9 group. BSA ratio <0.9 conferred an increased risk of graft loss (adjusted hazard ratio, 1.61; 95% confidence interval, 1.13-2.27; P=0.008). Patients with a donor/recipient BSA ratio >= 0.9 group had a significantly longer graft survival compared with those with a donor/recipient BSA ratio <0.9 after adjustment for donor age and gender, recipient age, gender, ethnicity, cause of renal failure, as well as clinical factors, such as cold and warm ischemia time and HLA mismatch. Conclusion. We conclude that low donor/recipient BSA ratio was associated with an increased risk of graft loss. Appropriate size matching conferred better long-term graft survival in adolescents receiving live-donor kidney transplants. C1 [Dick, Andre A. S.; Healey, Patrick J.] Seattle Childrens Hosp, Dept Surg, Div Pediat Transplantat, Seattle, WA 98105 USA. [Dick, Andre A. S.; Healey, Patrick J.] Univ Washington, Med Ctr, Seattle, WA 98105 USA. [Mercer, Laina D.] Seattle Childrens Res Inst, Core Biomed Stat, Seattle, WA USA. [Smith, Jodi M.; McDonald, Ruth A.] Seattle Childrens, Dept Pediat, Div Nephrol, Seattle, WA USA. [Young, Bessie] Univ Washington, Kidney Res Inst, VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98105 USA. RP Dick, AAS (reprint author), Seattle Childrens Hosp, Dept Surg, Div Pediat Transplantat, 4800 Sand Point Way Northeast,M-S W-7800, Seattle, WA 98105 USA. EM Andre.dick@seattlechildrens.org FU Seattle Children's Center for Clinical and Translational Research Faculty Research Support Fund; Center for Clinical and Translational Research at the Seattle Children's Research Institute; National Institutes of Health/National Center for Research Resources [UL1RR025014]; VA Puget Sound; National Institutes of Health [DK079745] FX This publication was funded by the Seattle Children's Center for Clinical and Translational Research Faculty Research Support Fund. The Seattle Children's Core for Biomedical Statistics is supported by the Center for Clinical and Translational Research at the Seattle Children's Research Institute and the National Institutes of Health/National Center for Research Resources grant UL1RR025014. B.Y. is supported by the VA Puget Sound and by the National Institutes of Health grant DK079745. NR 24 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP PY 2013 VL 96 IS 6 BP 555 EP 559 DI 10.1097/TP.0b013e31829d672c PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 299GK UT WOS:000330383900013 PM 23838999 ER PT J AU Sun, HY Cacciarelli, TV Singh, N AF Sun, Hsin-Yun Cacciarelli, Thomas V. Singh, Nina TI Micafungin Versus Amphotericin B Lipid Complex for the Prevention of Invasive Fungal Infections in High-Risk Liver Transplant Recipients SO TRANSPLANTATION LA English DT Article DE Fungal infections; Liver transplant; Antifungal prophylaxis ID SOLID-ORGAN TRANSPLANTATION; ANTIFUNGAL PROPHYLAXIS; PREEMPTIVE THERAPY; ASPERGILLOSIS; CYTOMEGALOVIRUS; VALGANCICLOVIR; FORMULATIONS; CASPOFUNGIN; MANAGEMENT; MORTALITY AB Background. Limited data exist regarding echinocandins as antifungal prophylaxis in liver transplant recipients. Methods. The efficacy and safety of targeted prophylaxis with micafungin or amphotericin B lipid complex (ABLC) was assessed in a sequential cohort of high-risk patients (posttransplantation dialysis, retransplantation, or reoperation) and compared with those without high risk who did not receive prophylaxis. Outcomes were assessed at 90 days. Results. Micafungin versus ABLC recipients were older (P=0.0065) and more likely to have hepatocellular carcinoma (P=0.025). High-risks, that is, dialysis (55.6% vs. 79.2%), retransplantation (5.6% vs. 12.5%), and reoperation (38.9% vs. 20.8%) did not differ between the two groups. Invasive fungal infections developed in 11.1% (2 of 18) of micafungin recipients, 8.3% (2 of 24) of ABLC recipients, and 3% (7 of 234) of patients without high risks (P=0.12). In nondialyzed patients, ABLC versus micafungin recipients had significantly higher serum creatinine on day 14 (P=0.04). However, renal and hepatic function, rejection, graft loss, and mortality did not differ for the two groups on day 90. Conclusions. Targeted prophylaxis with micafungin or ABLC decreased the risk of mycoses in high-risk recipients compared with that in low-risk recipients. Compared with ABLC, however, micafungin appeared to be associated with lower early-renal dysfunction and no additional risk of hepatic dysfunction. C1 [Sun, Hsin-Yun; Cacciarelli, Thomas V.; Singh, Nina] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Cacciarelli, Thomas V.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. RP Singh, N (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu OI SUN, HSIN-YUN/0000-0003-0074-7721 FU Astellas; Pfizer, Inc.; Astellas Pharma FX This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Pittsburgh Healthcare System (Pittsburgh, PA). The contents do not represent the views of the Department of Veterans Affairs or the U.S. Government. The study was supported through an investigator-initiated grant program of Astellas. The sponsor had no role in study design, conduct, analyses, and interpretation of the results. N.S. has received research support from Pfizer, Inc., and Astellas Pharma. NR 28 TC 16 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP PY 2013 VL 96 IS 6 BP 573 EP 578 DI 10.1097/TP.0b013e31829d674f PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 299GK UT WOS:000330383900016 PM 23842191 ER PT J AU Martins, PNA McDaid, J Markmann, JF AF Martins, Paulo Ney Aguiar McDaid, James Markmann, James F. TI Left Accessory Hepatic Artery Damage by a Misplaced Gastric Band in a Deceased Liver Donor SO TRANSPLANTATION LA English DT Letter ID ANATOMY C1 [Martins, Paulo Ney Aguiar; McDaid, James; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Transplant Div, Boston, MA 02114 USA. RP Martins, PNA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Transplant Div, 55 Fruit St, Boston, MA 02114 USA. EM pnmartins@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP PY 2013 VL 96 IS 6 BP E45 EP E46 DI 10.1097/TP.0b013e3182a1c253 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 299GK UT WOS:000330383900001 PM 24042978 ER PT J AU Zelop, CM Javitt, MC Glanc, P Dubinsky, T Harisinghani, MG Harris, RD Khati, NJ Mitchell, DG Pandharipande, PV Pannu, HK Podrasky, AE Shipp, TD Siegel, CL Simpson, L Wall, DJ Wong-You-Cheong, JJ AF Zelop, Carolyn M. Javitt, Marcia C. Glanc, Phyllis Dubinsky, Theodore Harisinghani, Mukesh G. Harris, Robert D. Khati, Nadia J. Mitchell, Donald G. Pandharipande, Pari V. Pannu, Harpreet K. Podrasky, Ann E. Shipp, Thomas D. Siegel, Cary Lynn Simpson, Lynn Wall, Darci J. Wong-You-Cheong, Jade J. TI ACR Appropriateness Criteria (R) Growth Disturbances-Risk of Intrauterine Growth Restriction SO ULTRASOUND QUARTERLY LA English DT Article DE appropriateness criteria; fetal growth disturbances; risk of intrauterine growth restriction ID UMBILICAL ARTERY VELOCIMETRY; DOPPLER ULTRASONOGRAPHY; FETAL-GROWTH; RETARDATION; PREGNANCIES; ULTRASOUND; PREDICTOR; DIAGNOSIS; FETUSES; BLOOD AB Fetal growth disturbances include fetuses at risk for intrauterine growth restriction. These fetuses may have an estimated fetal weight at less than the 10% or demonstrate a plateau of fetal growth with an estimated fetal growth greater than the 10%. Uteroplacental insufficiency may play a major role in the etiology of intrauterine growth restriction. Fetuses at risk for intrauterine fetal growth restriction are susceptible to the potential hostility of the intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal movement counting. 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 [Zelop, Carolyn M.] Valley Hosp, Ridgewood, NJ USA. [Javitt, Marcia C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA. [Harisinghani, Mukesh G.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Khati, Nadia J.] George Washington Univ Hosp, Washington, DC USA. [Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Pannu, Harpreet K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Podrasky, Ann E.] Baptist Hosp Miami, South Miami Ctr forWomen & Infants, Miami, FL USA. [Shipp, Thomas D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Simpson, Lynn] Columbia Univ, New York, NY USA. [Wall, Darci J.] Mayo Clin, Rochester, MN USA. [Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Zelop, CM (reprint author), Amer Coll Radiol, Dept Qual & Safety, 1891 Preston White Dr, Reston, VA 20191 USA. EM cmzelop@comcast.net NR 29 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD SEP PY 2013 VL 29 IS 3 BP 147 EP 151 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 300EE UT WOS:000330446400002 PM 23867573 ER PT J AU Oyedeji, F Giampoli, E Ginat, D Dogra, V AF Oyedeji, Francisca Giampoli, Ellen Ginat, Daniel Dogra, Vikram TI The Sonographic Appearance of Benign and Malignant Thyroid Diseases and Their Histopathology Correlate Demystifying the Thyroid Nodule SO ULTRASOUND QUARTERLY LA English DT Article DE Comet tail artifact; rim calcifications; spongiform appearance; microcalcifications; hypervascularity; thyroid; ultrasound; color Doppler; papillary carcinoma; Hashimoto disease; anaplastic carcinoma; primary thyroid lymphoma; Graves disease ID FINE-NEEDLE-ASPIRATION; LOW-RISK PATIENTS; FOLLICULAR ADENOMA; LYMPH-NODES; HASHIMOTOS-THYROIDITIS; SERUM THYROGLOBULIN; CARCINOMA; ULTRASOUND; PAPILLARY; FEATURES AB The thyroid gland is one of the largest endocrine glands in the human body. It functions as a regulator of metabolism. Diseases involving the thyroid range from benign to malignant and can be associated with major morbidity and mortality. Ultrasound (US) imaging of the thyroid gland is prompted because of a palpable mass on clinical examination; abnormality of thyroid function tests; incidental finding on other imaging modalities, that is, nuclear scintigraphy or computed tomography scan; screening for patients with risk factors for malignancy, such as multiple endocrine neoplasia type II; or prior neck radiation treatment. Ultrasound is an excellent, noninvasive, and cost-effective diagnostic tool in the detection and characterization of thyroid disease. Most thyroid diseases have pathognomonic features on US, which are of diagnostic importance and lead to appropriate clinical management. Ultrasound plays an important role in differentiating benign from malignant thyroid disease, thereby triaging patients for US-guided fine-needle aspiration. Ultimately, thyroid US, in conjunction with thyroid function tests, can aid in characterizing various thyroid diseases. The main objective of this pictorial essay is to illustrate the sonographic appearance of various benign and malignant diseases of the thyroid with their histopathology correlations. Management of thyroid nodules using US-guided fine-needle aspiration is also briefly discussed. C1 [Oyedeji, Francisca; Dogra, Vikram] Univ Rochester, Med Ctr, Dept Radiol, Rochester, NY 14642 USA. [Giampoli, Ellen] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA. [Ginat, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dogra, V (reprint author), Univ Rochester, Med Ctr, 601 Elmwood Ave,Box 648, Rochester, NY 14642 USA. EM Vikram.Dogra54@gmail.com NR 80 TC 2 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD SEP PY 2013 VL 29 IS 3 BP 161 EP 178 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 300EE UT WOS:000330446400005 PM 23867569 ER PT J AU Rao, M Concannon, TW Iovin, R Yu, WW Chan, JA Lypas, G Terasawa, T Gaylor, JM Kong, LN Rausch, AC Lau, J Kitsios, GD AF Rao, Madhu Concannon, Thomas W. Iovin, Ramon Yu, Winifred W. Chan, Jeffrey A. Lypas, Georgios Terasawa, Teruhiko Gaylor, James M. Kong, Lina Rausch, Andrew C. Lau, Joseph Kitsios, Georgios D. TI Identification of topics for comparative effectiveness systematic reviews in the field of cancer imaging SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH LA English DT Article DE cancer imaging; comparative effectiveness reviews; environmental scan; research prioritization; stakeholders; topic identification ID CENTERED OUTCOMES RESEARCH; STAKEHOLDER ENGAGEMENT; UNITED-STATES; PRIORITIES; TIME AB Aim: With rapid innovations in diagnostic and therapeutic interventions in cancer care, comparative effectiveness reviews (CERs) are essential to inform clinical practice and guide future research. However, the optimal means to identify priority CER topics are uninvestigated. We aimed to devise a transparent and reproducible process to identify ten to 12 CER topics in the area of cancer imaging relevant to a wide range of stakeholders. Materials & methods: Environmental scans and explicit prioritization criteria supported interactions (email communications, web-based discussions and live teleconferences) with experts and stakeholders culminating in a three-phase deductive exercise for prioritization of CER topics. Results: We prioritized 12 CER topics in breast, lung and gastrointestinal cancers that addressed screening, diagnosis, staging, monitoring and evaluating response to treatment. Conclusion: Our project developed and implemented a transparent and reproducible process for research prioritization and topic nomination that can be further refined to improve the relevance of future CERs. C1 [Rao, Madhu; Iovin, Ramon; Yu, Winifred W.; Chan, Jeffrey A.; Terasawa, Teruhiko; Gaylor, James M.; Kong, Lina; Rausch, Andrew C.; Kitsios, Georgios D.] Tufts Med Ctr, ICRHPS, Boston, MA 02111 USA. [Rao, Madhu; Iovin, Ramon; Yu, Winifred W.; Chan, Jeffrey A.; Terasawa, Teruhiko; Gaylor, James M.; Kong, Lina; Rausch, Andrew C.; Kitsios, Georgios D.] Tufts Univ, Sch Med, Boston, MA USA. [Rao, Madhu] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Concannon, Thomas W.] RAND Corp, Boston, MA 02111 USA. [Lypas, Georgios] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lypas, Georgios] Hygeia Hosp, Genet Oncol Unit, Athens, Greece. [Terasawa, Teruhiko] Fujita Hlth Univ, Sch Med, Dept Internal Med, Tsu, Mie, Japan. [Lau, Joseph] Brown Univ, Brown Ctr Evidence Based Med, Providence, RI 02912 USA. [Kitsios, Georgios D.] Lahey Hosp & Med Ctr, Dept Internal Med, Burlington, MA 01805 USA. RP Kitsios, GD (reprint author), Tufts Med Ctr, ICRHPS, Boston, MA 02111 USA. EM georgios.kitsios@lahey.org OI , /0000-0002-6834-7583 FU Agency for Healthcare Research and Quality [HHSA-290-2007-10055-I] FX This work was supported by the Agency for Healthcare Research and Quality, Contract HHSA-290-2007-10055-I, Task Order 7. 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 24 TC 1 Z9 1 U1 3 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 2042-6305 EI 2042-6313 J9 J COMP EFFECT RES JI J. Comp. Eff. Res. PD SEP PY 2013 VL 2 IS 5 BP 483 EP 495 DI 10.2217/cer.13.61 PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 297DX UT WOS:000330236700018 PM 24236745 ER PT J AU Noseworthy, PA Baggish, AL AF Noseworthy, Peter A. Baggish, Aaron L. TI The prevalence and clinical significance of J wave patterns in athletes SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article ID EARLY REPOLARIZATION PATTERN; VENTRICULAR-FIBRILLATION; BRUGADA-SYNDROME; ELECTROCARDIOGRAMS; ABNORMALITIES; POPULATION; VARIANT; DEATH C1 [Noseworthy, Peter A.; Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Baggish, Aaron L.] Harvard Univ, Hlth Serv, Cambridge, MA 02138 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org NR 25 TC 3 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD SEP-OCT PY 2013 VL 46 IS 5 BP 424 EP 426 DI 10.1016/j.jelectrocard.2013.06.021 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 297QA UT WOS:000330268800011 PM 23981309 ER PT J AU Rondas, D Bugliani, M D'Hertog, W Lage, K Masini, M Waelkens, E Marchetti, P Mathieu, C Overbergh, L AF Rondas, Dieter Bugliani, Marco D'Hertog, Wannes Lage, Kasper Masini, Mathilde Waelkens, Etienne Marchetti, Piero Mathieu, Chantal Overbergh, Lut TI Glucagon-Like Peptide-1 Protects Human Islets against Cytokine-Mediated beta-Cell Dysfunction and Death: A Proteomic Study of the Pathways Involved SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE GLP-1; Type 1 diabetes; human islets; cytokines; 2D-DIGE; protein interaction networks ID STIMULATED INSULIN-SECRETION; ENDOPLASMIC-RETICULUM STRESS; ANTI-APOPTOTIC ACTION; POSTTRANSLATIONAL MODIFICATIONS; GENE-EXPRESSION; DIABETIC MICE; RAT ISLETS; ACTIN; EXENDIN-4; TYPE-1 AB Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic beta-cells against cytokine-induced dysfunction and destruction. The mechanisms through which GLP-1 exerts its effects are complex and still poorly understood. The aim of this study was to analyze the protein expression profiles of human islets of Langerhans treated with cytokines (IL-1 beta and IFN-gamma) in the presence or absence of GLP-1 by 2D difference gel electrophoresis and subsequent protein interaction network analysis to understand the molecular pathways involved in GLP-1-mediated beta-cell protection. Co-incubation of cytokine-treated human islets with GLP-1 resulted in a marked protection of beta-cells against cytokine-induced apoptosis and significantly attenuated cytokine-mediated inhibition of glucose-stimulated insulin secretion. The cytoprotective effects of GLP-1 coincided with substantial alterations in the protein expression profile of cytokine-treated human islets, illustrating a counteracting effect on proteins from different functional classes such as actin cytoskeleton, chaperones, metabolic proteins, and islet regenerating proteins. In summary, GLP-1 alters in an integrated manner protein networks in cytokine-exposed human islets while protecting them against cytokine-mediated cell death and dysfunction. These data illustrate the beneficial effects of GLP-1 on human islets under immune attack, leading to a better understanding of the underlying mechanisms involved, a prerequisite for improving therapies for diabetic patients. C1 [Rondas, Dieter; D'Hertog, Wannes; Mathieu, Chantal; Overbergh, Lut] Katholieke Univ Leuven, Lab Clin & Expt Endocrinol, B-3000 Louvain, Belgium. [Waelkens, Etienne] Katholieke Univ Leuven, Lab Prot Phosphorylat & Prote, B-3000 Louvain, Belgium. [Bugliani, Marco; Masini, Mathilde; Marchetti, Piero] Univ Pisa, Dept Endocrinol & Metab, I-56124 Pisa, Italy. [Lage, Kasper] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Lage, Kasper] Massachusetts Gen Hosp, Pediat Surg Res Labs, MassGen Hosp Children, Boston, MA 02114 USA. [Lage, Kasper] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Overbergh, L (reprint author), Katholieke Univ Leuven, Lab Clin & Expt Endocrinol, Herestr 49, B-3000 Louvain, Belgium. EM lut.overbergh@med.kuleuven.be RI Marchetti, Piero/J-7439-2013 OI Marchetti, Piero/0000-0003-4907-0635 FU European Community [241447]; KU Leuven (Geconcerteerde Onderzoeksactie) [GOA 12/24]; Flemish Research Foundation [FWO G.0649.08, G.0619.12]; Juvenile Diabetes Research Foundation International [17-2012-129]; Interuniversity Attraction Poles Program-Belgian Federal Science Policy [P7/13] FX The technical experience of Eefje Verdrengh and Sandy Vandoninck is greatly appreciated. This work was supported by the European Community's seventh Framework Programme NAIMIT under grant agreement no. 241447, the KU Leuven (Geconcerteerde Onderzoeksactie 2009/10 and GOA 12/24), the Flemish Research Foundation (FWO G.0649.08, G.0619.12 and a clinical research fellowship for C.M.) and the Juvenile Diabetes Research Foundation International (17-2012-129), and a grant of the Interuniversity Attraction Poles Program (P7/13)-Belgian Federal Science Policy. NR 56 TC 12 Z9 12 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD SEP PY 2013 VL 12 IS 9 BP 4193 EP 4206 DI 10.1021/pr400527q PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 295WT UT WOS:000330147800033 PM 23937086 ER PT J AU Yonekawa, Y Orbach, DB Trief, D Shah, AS VanderVeen, DK AF Yonekawa, Yoshihiro Orbach, Darren B. Trief, Danielle Shah, Ankoor S. VanderVeen, Deborah K. TI Intra-arterial Chemotherapy for Group C Retinoblastoma With Adjacent High-flow Infantile Hemangioma SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID INTRAOPHTHALMIC ARTERY CHEMOTHERAPY; INTRAOCULAR RETINOBLASTOMA; MANAGEMENT; MELPHALAN; INJECTION; ANATOMY AB Intra-arterial chemotherapy for retinoblastoma is an emerging technique that is being adopted at various centers worldwide. The authors report the first case of an infantile hemangioma that shunted flow during intra-arterial chemotherapy in a 4-month-old girl who presented with macular group C retinoblastoma. Excellent tumor response was noted despite only a fraction of the dose entering the central retinal artery. Further studies to examine intra-arterial chemotherapy's pharmacokinetics and dose-response relations are warranted in order to minimize the necessary exposure to chemotherapy. C1 [Yonekawa, Yoshihiro; Orbach, Darren B.; Trief, Danielle; Shah, Ankoor S.; VanderVeen, Deborah K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston Childrens Hosp,Dept Radiol,Dept Ophthalmol, Boston, MA USA. RP Shah, AS (reprint author), Boston Childrens Hosp, Dept Ophthalmol, Fegan 4,300 Longwood Ave, Boston, MA 02115 USA. EM ankoor.shah@childrens.harvard.edu RI Orbach, Darren/M-5773-2013 OI Orbach, Darren/0000-0002-1793-3398 NR 16 TC 0 Z9 0 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 SEP-OCT PY 2013 VL 44 IS 5 BP 490 EP 492 DI 10.3928/23258160-20130909-13 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 296NS UT WOS:000330192400012 PM 24044714 ER PT J AU Nicholson, L Sobrin, L AF Nicholson, Laura Sobrin, Lucia TI The Use of Pars Plana Vitrectomy in the Treatment of a Serous Retinal Detachment Secondary to Lupus Choroidopathy SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID UVEAL EFFUSION SYNDROME AB This report describes the use of pars plana vitrectomy (PPV) in the management of a patient with a serous retinal detachment (SRD) secondary to lupus choroidopathy. Surgery was performed after anti-inflammatory treatments and laser photocoagulation failed to resolve the condition. The patient's vision improved, and the subretinal fluid has not reaccumulated at 5 years postoperatively. The high viscosity of the subretinal fluid observed during the procedure may account for the persistence of the SRD despite control of inflammation. PPV surgery can be considered as a treatment option for patients with lupus-related SRD when anti-inflammatory medications are not successful and the subretinal fluid does not reabsorb independently. C1 [Nicholson, Laura; Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Sobrin, L (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St,12th floor, Boston, MA 02114 USA. EM Lucia_Sobrin@meei.harvard.edu NR 8 TC 0 Z9 0 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 SEP-OCT PY 2013 VL 44 IS 5 BP 502 EP 504 DI 10.3928/23258160-20130909-17 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 296NS UT WOS:000330192400016 PM 24044718 ER PT J AU Sibila, O Laserna, E Mortensen, EM Anzueto, A Restrepo, MI AF Sibila, Oriol Laserna, Elena Mortensen, Eric M. Anzueto, Antonio Restrepo, Marcos I. TI Effects of Inhaled Corticosteroids on Pneumonia Severity and Antimicrobial Resistance SO RESPIRATORY CARE LA English DT Article DE drug resistance; inhaled corticosteroids; pneumonia; severity of illness index ID OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; LONG-TERM USE; COPD PATIENTS; SALMETEROL/FLUTICASONE PROPIONATE; RISK-FACTORS; METAANALYSIS; SALMETEROL; EXACERBATIONS; FLUTICASONE AB BACKGROUND: Limited information is available regarding the impact of prior use of inhaled corticosteroids (ICS) in patients subsequently developing community-acquired pneumonia (CAP). We assessed the effects of prior ICS use on severity of illness and microbiology in CAP hospitalized patients. METHODS: A retrospective cohort study of subjects with CAP (by the International Classification of Diseases, 9th Revision, Clinical Modification) was conducted over a 4-year period at 2 tertiary teaching hospitals. Subjects were considered to be ICS users if they received ICS prior to admission. Primary outcomes were severity of illness and microbiology at admission. RESULTS: Data were abstracted on 664 subjects: 89 prior ICS users (13.4%) and 575 non-users (86.6%). Prior ICS users had higher severity of illness at admission: mean +/- SD Pneumonia Severity Index 100.8 +/- 31.4 vs 68.8 +/- 33.4, P = .001, and CURB-65 (confusion, urea nitrogen, respiratory rate, blood pressure, >= 65 years of age) score 1.56 +/- 1.02 vs 1.19 +/- 1.02, P = .002. Prior ICS use was independently associated with antimicrobial-resistant pathogens: 11.2% vs 5.9%, odds ratio 2.6, 95% CI 1.1-6.1, P = .04. CONCLUSIONS: Prior ICS use was associated with higher severity of illness at admission and higher incidence of antimicrobial-resistant pathogens in CAP hospitalized patients. C1 [Sibila, Oriol; Laserna, Elena; Anzueto, Antonio; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mortensen, Eric M.] Vet Affairs North Texas Hlth Care Syst, San Antonio, TX 78229 USA. [Mortensen, Eric M.] Univ Texas Sothwestern Med Ctr, San Antonio, TX USA. [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain. [Laserna, Elena] Hosp Comarcal Mollet, Mollet Del Valles, Spain. [Anzueto, Antonio; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst, ALMD 7400,Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Howard Hughes Medical Institute [00378-001]; Department of Veteran Affairs Veterans Integrated Service Network 17; Instituto de Salud Carlos III [BAE11/00102]; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR); Societat Catalana de Pneumologia; Fundacio Catalana de Pneumologia; National Heart, Lung, and Blood Institute [K23HL096054] FX Dr Anzueto has disclosed a relationship with Boehringer Ingelheim, GlaxoSmithKline, Forest Laboratories, Astra-Zeneca, Pfizer, Intermune, Amgen, Bayer-Schering Pharma, Lilly, and the National Institutes of Health. Dr Restrepo has disclosed relationships with Theravance, Forest Laboratories, Johnson & Johnson, Trius, Novartis, and Pfizer. This research was supported by Howard Hughes Medical Institute faculty start-up grant 00378-001, and by a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant. Dr Sibila was supported by Instituto de Salud Carlos III (BAE11/00102). Drs Sibila and Laserna were supported by Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Societat Catalana de Pneumologia and Fundacio Catalana de Pneumologia. Dr Restrepo was partly supported grant K23HL096054 from the National Heart, Lung, and Blood Institute. The funding agencies had no role in the preparation, review, or approval of the manuscript. The views expressed in this report are those of the authors and do not represent the views of the Department of Veterans Affairs. NR 33 TC 5 Z9 5 U1 0 U2 0 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 SEP PY 2013 VL 58 IS 9 BP 1489 EP 1494 DI 10.4187/respcare.02191 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 295EP UT WOS:000330099700011 PM 23345471 ER PT J AU Schatz, CJ Ginat, DT AF Schatz, C. J. Ginat, D. T. TI Imaging of Cosmetic Facial Implants and Grafts SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID CHIN AUGMENTATION; MALAR AUGMENTATION; LIP AUGMENTATION; TURKISH DELIGHT; LATE INFECTION; RHINOPLASTY; RECONSTRUCTION; REJUVENATION; EROSION AB A wide variety of implants and grafts have been used for cosmetic facial surgery, including forehead, nose, cheek, lip, and chin augmentation. Some of the implant materials include silicone, expanded polytetrafluoroethylene (Gore-Tex), hydroxylapatite, and porous polyethylene (Medpor). Grafts include bone and cartilage, which can be prepared as Turkish Delight for rhinoplasty. Imaged facial implants and grafts can be encountered incidentally or purposely to evaluate complications. Many of these materials have distinct radiologic imaging features and should not be misinterpreted as pathology. Conversely, implant complications should be appropriately recognized by using a focused imaging approach. The purpose of this article was to review the different types of cosmetic facial implants and grafts with an emphasis on their expected and complicated radiologic imaging appearances. C1 [Schatz, C. J.] Beverly Tower Wilshire Adv Imaging, Beverly Hills, CA USA. [Schatz, C. J.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Ginat, D. T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ginat, D. T.] Harvard Univ, Sch Med, Boston, MA USA. RP Ginat, DT (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 44 TC 4 Z9 4 U1 0 U2 3 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 SEP PY 2013 VL 34 IS 9 BP 1674 EP 1681 DI 10.3174/ajnr.A3214 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 291SE UT WOS:000329848800009 PM 22878009 ER PT J AU Sabin, AT Gallun, FJ Souza, PE AF Sabin, Andrew T. Gallun, Frederick J. Souza, Pamela E. TI Acoustical correlates of performance on a dynamic range compression discrimination task SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MODULATION TRANSFER-FUNCTIONS; HEARING-AID; AMPLITUDE-MODULATION; GAP DETECTION; SPECTROTEMPORAL MODULATION; SPEECH-INTELLIGIBILITY; RELEASE TIME; NOISE; RECOGNITION; FREQUENCY AB Dynamic range compression is widely used to reduce the difference between the most and least intense portions of a signal. Such compression distorts the shape of the amplitude envelope of a signal, but it is unclear to what extent such distortions are actually perceivable by listeners. Here, the ability to distinguish between compressed and uncompressed versions of a noise vocoded sentence was initially measured in listeners with normal hearing while varying the threshold, ratio, attack, and release parameters. This narrow condition was selected in order to characterize perception under the most favorable listening conditions. The average behavioral sensitivity to compression was highly correlated to several acoustical indices of modulation depth. In particular, performance was highly correlated to the Euclidean distance between the modulation spectra of the uncompressed and compressed signals. Suggesting that this relationship is not restricted to the initial test conditions, the correlation remained largely unchanged both (1) when listeners with normal hearing were tested using a time-compressed version of the original signal, and (2) when listeners with impaired hearing were tested using the original signal. If this relationship generalizes to more ecologically valid conditions, it will provide a straightforward method for predicting the detectability of compression-induced distortions. (C) 2013 Acoustical Society of America. C1 [Sabin, Andrew T.; Souza, Pamela E.] Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL 60201 USA. [Gallun, Frederick J.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res NCRAR, Portland, OR 97239 USA. [Gallun, Frederick J.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97239 USA. RP Sabin, AT (reprint author), Northwestern Univ, Dept Commun Sci & Disorders, 2240 Campus Dr, Evanston, IL 60201 USA. EM a-sabin@northwestern.edu FU NIH [DC60014]; Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (Center of Excellence Award) [C4844C] FX Efoe Nyatepe-Coo and Alex Evanoff helped with data collected. Morten Jepsen, Eric Hoover and Richard Wright provided helpful conversations in the development of this work. This work was funded by NIH grant DC60014 and by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (Center of Excellence Award C4844C). NR 54 TC 3 Z9 3 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2013 VL 134 IS 3 BP 2136 EP 2147 DI 10.1121/1.4816410 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 294LG UT WOS:000330047000041 PM 23967944 ER PT J AU Brill, A Suidan, GL Wagner, DD AF Brill, A. Suidan, G. L. Wagner, D. D. TI Hypoxia, such as encountered at high altitude, promotes deep vein thrombosis in mice SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID WEIBEL-PALADE BODIES; HUMAN-ENDOTHELIAL CELLS; VON-WILLEBRAND-FACTOR; AIR-TRAVEL; VENOUS THROMBOEMBOLISM; PLATELET-ADHESION; RISK-FACTOR; PROTEIN; DISEASE; INJURY C1 [Brill, A.; Suidan, G. L.; Wagner, D. D.] Immune Dis Inst, Boston, MA USA. [Brill, A.; Suidan, G. L.; Wagner, D. D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Brill, A.; Suidan, G. L.; Wagner, D. D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wagner, D. D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM Denisa.Wagner@childrens.harvard.edu FU NHLBI NIH HHS [P01 HL066105, R01 HL041002, R01 HL095091]; NINDS NIH HHS [1F32NS073245, F32 NS073245] NR 21 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD SEP PY 2013 VL 11 IS 9 BP 1773 EP 1775 DI 10.1111/jth.12310 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 216UU UT WOS:000324311400019 PM 23742235 ER PT J AU Yoo, AJ Simonsen, CZ Prabhakaran, S Chaudhry, ZA Issa, MA Fugate, JE Linfante, I Liebeskind, DS Khatri, P Jovin, TG Kallmes, DF Dabus, G Zaidat, OO AF Yoo, Albert J. Simonsen, Claus Z. Prabhakaran, Shyam Chaudhry, Zeshan A. Issa, Mohammad A. Fugate, Jennifer E. Linfante, Italo Liebeskind, David S. Khatri, Pooja Jovin, Tudor G. Kallmes, David F. Dabus, Guilherme Zaidat, Osama O. CA Cerebral Angiographic TI Refining Angiographic Biomarkers of Revascularization Improving Outcome Prediction After Intra-arterial Therapy SO STROKE LA English DT Article DE acute ischemic stroke; endovascular; intra-arterial therapy; modified TICI; revascularization; TIMI ID ACUTE ISCHEMIC-STROKE; RECANALIZATION; TRIAL; THROMBOLYSIS; THROMBECTOMY; REPERFUSION AB Background and Purpose Angiographic revascularization grading after intra-arterial stroke therapy is limited by poor standardization, making it unclear which scale is optimal for predicting outcome. Using recently standardized criteria, we sought to compare the prognostic performance of 2 commonly used reperfusion scales. Methods Inclusion criteria for this multicenter retrospective study were acute ischemic stroke attributable to middle cerebral artery M1 occlusion, intra-arterial therapy, and 90-day modified Rankin scale score. Post-intra-arterial therapy reperfusion was graded using the Thrombolysis in Myocardial Infarction (TIMI) and Modified Thrombolysis in Cerebral Infarction (mTICI) scales. The scales were compared for prediction of clinical outcome using receiver-operating characteristic analysis. Results Of 308 patients, mean age was 65 years, and median National Institutes of Health Stroke Scale score was 17. The mean time from stroke onset to groin puncture was 305 minutes. There was no difference in the time to treatment between patients grouped by final TIMI (ie, 0 versus 1 versus 2 versus 3) or mTICI grades (ie, 0 versus 1 versus 2a versus 2b versus 3). Good outcome (modified Rankin scale, 0-2) was achieved in 32.5% of patients, and mortality rate was 25.3% at 90 days. There was a 6.3% rate of parenchymal hematoma type 2. In receiver-operating characteristic analysis, mTICI was superior to TIMI for predicting 90-day modified Rankin scale 0 to 2 (c-statistic: 0.74 versus 0.68; P<0.0001). The optimal threshold for identifying a good outcome was mTICI 2b to 3 (sensitivity 78.0%; specificity 66.1%). Conclusions mTICI is superior to TIMI for predicting clinical outcome after intra-arterial therapy. mTICI 2b to 3 is the optimal biomarker for procedural success. C1 [Yoo, Albert J.; Chaudhry, Zeshan A.] Massachusetts Gen Hosp, Div Intervent Neuroradiol, Boston, MA 02114 USA. [Simonsen, Claus Z.] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus, Denmark. [Prabhakaran, Shyam] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. [Issa, Mohammad A.; Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurol Neurosurg & Radiol, Milwaukee, WI 53226 USA. [Fugate, Jennifer E.; Kallmes, David F.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Linfante, Italo; Dabus, Guilherme] Baptist Cardiac & Vasc Inst, Div Neurointervent Surg, Miami, FL USA. [Liebeskind, David S.] UCLA Stroke Ctr, Los Angeles, CA USA. [Khatri, Pooja] Univ Cincinnati, Dept Neurol, Acad Hlth Ctr, Cincinnati, OH USA. [Jovin, Tudor G.] Univ Pittsburgh, Dept Neurol, Med Ctr, Pittsburgh, PA 15260 USA. [Prabhakaran, Shyam] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Yoo, AJ (reprint author), Div Diagnost & Intervent Neuroradiol, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org FU National Institutes of Health (NIH); Penumbra Inc; Remedy Pharmaceuticals; Genentech; Stryker; Codman Neurovascular; Covidien; MicroVention; Sequent; Reverse Medical; Gore Medical FX Dr Yoo receives research funding from the National Institutes of Health (NIH), Penumbra Inc, and Remedy Pharmaceuticals. Dr Prabhakaran receives research funding from Genentech. Dr Linfante receives consulting fees and expenses from Stryker and Codman Neurovascular. Dr Liebeskind receives consulting fees and expenses from Stryker and Covidien. Dr Khatri receives research funding from NIH, Penumbra Inc, and Genentech. Dr Kallmes receives research funding from MicroVention, Codman Neurovascular, Sequent, and Covidien, and receives consulting fees and expenses from Codman Neurovascular and Covidien. Dr Dabus receives consulting fees and expenses from Covidien, Codman Neurovascular, and Reverse Medical. Dr Zaidat is an equity shareholder in Galaxy Therapeutics and receives consulting fees and expenses from Stryker and Gore Medical. NR 16 TC 31 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2013 VL 44 IS 9 BP 2509 EP 2512 DI 10.1161/STROKEAHA.113.001990 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 293OP UT WOS:000329982500039 PM 23920017 ER PT J AU Miyamoto, N Pham, LDD Hayakawa, K Matsuzaki, T Seo, JH Magnain, C Ayata, C Kim, KW Boas, D Lo, EH Arai, K AF Miyamoto, Nobukazu Pham, Loc-Duyen D. Hayakawa, Kazuhide Matsuzaki, Toshinori Seo, Ji Hae Magnain, Caroline Ayata, Cenk Kim, Kyu-Won Boas, David Lo, Eng H. Arai, Ken TI Age-Related Decline in Oligodendrogenesis Retards White Matter Repair in Mice SO STROKE LA English DT Article DE aging; animal model; cyclic AMP response element-binding protein; oligodendrocyte; white matter diseases ID DENTATE GYRUS; STROKE; NEUROGENESIS; HIPPOCAMPUS; IMPAIRMENT; EXPRESSION; CILOSTAZOL; DECREASE; INJURY; MYELIN AB Background and Purpose Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury. Methods A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month-old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells to sublethal 7-day CoCl2 treatment to induce chemical hypoxic stress. Results Baseline myelin density in the corpus callosum was similar in 2-month and 8-month-old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in cyclic AMP response element-binding protein signaling may be involved because activating cyclic AMP response element-binding protein with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of oligodendrocyte precursor cells. Conclusions An age-related decline in cyclic AMP response element-binding protein-mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate cyclic AMP response element-binding protein signaling provide a potential therapeutic approach for treating white matter injury in aging brains. C1 [Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Boston, MA 02114 USA. [Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Boston, MA 02114 USA. [Magnain, Caroline; Boas, David] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul, South Korea. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU Deane Foundation, Massachusetts General Hospital (MGH) Executive Committee on Research (ECOR) Fund for Medical Discovery; American Heart Association; National Institutes of Health, Research Abroad from the Uehara Memorial Foundation; National Research Foundation of Korea [R31-2008-000-10103-0, 2011-0021874] FX This work was supported, in part, by the Deane Foundation, Massachusetts General Hospital (MGH) Executive Committee on Research (ECOR) Fund for Medical Discovery, the American Heart Association, the National Institutes of Health, Research Abroad from the Uehara Memorial Foundation, the National Research Foundation of Korea through the World Class University Program (R31-2008-000-10103-0) and the Global Research Laboratory Program (2011-0021874). NR 23 TC 23 Z9 24 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2013 VL 44 IS 9 BP 2573 EP 2578 DI 10.1161/STROKEAHA.113.001530 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 293OP UT WOS:000329982500049 PM 23881957 ER PT J AU Wintermark, M Albers, GW Broderick, JP Demchuk, AM Fiebach, JB Fiehler, J Grotta, JC Houser, G Jovin, TG Lees, KR Lev, MH Liebeskind, DS Luby, M Muir, KW Parsons, MW von Kummer, R Wardlaw, JM Wu, O Yoo, AJ Alexandrov, AV Alger, JR Aviv, RI Bammer, R Baron, JC Calamante, F Campbell, BCV Carpenter, TC Christensen, S Copen, WA Derdeyn, CP Haley, C Khatri, P Kudo, K Lansberg, MG Latour, LL Lee, TY Leigh, R Lin, WL Lyden, P Mair, G Menon, BK Michel, P Mikulik, R Nogueira, RG Ostergaard, L Pedraza, S Riedel, CH Rowley, HA Sanelli, PC Sasaki, M Saver, JL Schaefer, PW Schellinger, PD Tsivgoulis, G Wechsler, LR White, PM Zaharchuk, G Zaidat, OO Davis, SM Donnan, GA Furlan, AJ Hacke, W Kang, DW Kidwell, C Thijs, VN Thomalla, G Warach, SJ AF Wintermark, Max Albers, Gregory W. Broderick, Joseph P. Demchuk, Andrew M. Fiebach, Jochen B. Fiehler, Jens Grotta, James C. Houser, Gary Jovin, Tudor G. Lees, Kennedy R. Lev, Michael H. Liebeskind, David S. Luby, Marie Muir, Keith W. Parsons, Mark W. von Kummer, Ruediger Wardlaw, Joanna M. Wu, Ona Yoo, Albert J. Alexandrov, Andrei V. Alger, Jeffry R. Aviv, Richard I. Bammer, Roland Baron, Jean-Claude Calamante, Fernando Campbell, Bruce C. V. Carpenter, Trevor C. Christensen, Soren Copen, William A. Derdeyn, Colin P. Haley, Clarke, Jr. Khatri, Pooja Kudo, Kohsuke Lansberg, Maarten G. Latour, Lawrence L. Lee, Ting-Yim Leigh, Richard Lin, Weili Lyden, Patrick Mair, Grant Menon, Bijoy K. Michel, Patrik Mikulik, Robert Nogueira, Raul G. Ostergaard, Leif Pedraza, Salvador Riedel, Christian H. Rowley, Howard A. Sanelli, Pina C. Sasaki, Makoto Saver, Jeffrey L. Schaefer, Pamela W. Schellinger, Peter D. Tsivgoulis, Georgios Wechsler, Lawrence R. White, Philip M. Zaharchuk, Greg Zaidat, Osama O. Davis, Stephen M. Donnan, Geoffrey A. Furlan, Anthony J. Hacke, Werner Kang, Dong-Wha Kidwell, Chelsea Thijs, Vincent N. Thomalla, Goetz Warach, Steven J. CA Storke Imageing Res STIR Imaging Virtual Int Stroke Trials Archive TI Acute Stroke Imaging Research Roadmap II SO STROKE LA English DT Article DE angiography; clinical trial; computed tomography; consensus; imaging; magnetic resonance imaging; stroke; thrombolysis ID ACUTE ISCHEMIC-STROKE; MIDDLE CEREBRAL-ARTERY; TISSUE-PLASMINOGEN-ACTIVATOR; BRAIN-BARRIER DISRUPTION; INTRAVENOUS THROMBOLYSIS; HEMORRHAGIC TRANSFORMATION; INTRACEREBRAL HEMORRHAGE; CT ANGIOGRAPHY; PERFUSION; MRI C1 Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Wintermark, Max] CHU Vaudois, Dept Radiol, CH-1011 Lausanne, Switzerland. [Albers, Gregory W.; Bammer, Roland; Christensen, Soren; Lansberg, Maarten G.; Zaharchuk, Greg] Stanford Univ, Dept Neurol, Sch Med, Stanford, CA 94305 USA. [Broderick, Joseph P.; Khatri, Pooja] Univ Cincinnati, Dept Neurol, Inst Neurosci, Cincinnati, OH USA. [Demchuk, Andrew M.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB, Canada. [Demchuk, Andrew M.] Univ Calgary, Dept Radiol, Hotchkiss Brain Inst, Calgary, AB, Canada. [Menon, Bijoy K.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary Stroke Program, Calgary, AB, Canada. [Menon, Bijoy K.] Univ Calgary, Dept Radiol, Hotchkiss Brain Inst, Calgary Stroke Program, Calgary, AB, Canada. [Fiebach, Jochen B.] Charite, Ctr Stroke Res Berlin, Acad Neuroradiol, Dept Neurol, D-13353 Berlin, Germany. [Fiehler, Jens; Tsivgoulis, Georgios] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany. [Grotta, James C.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA. [Houser, Gary] Stroke Grp, Centennial, CO USA. [Jovin, Tudor G.] Univ Pittsburgh, Dept Neurol, Med Ctr, Stroke Inst, Pittsburgh, PA 15260 USA. [Jovin, Tudor G.] UPMC, Ctr Neuroendovasc Therapy, Pittsburgh, PA USA. [Lees, Kennedy R.] Univ Glasgow, Western Infirm, Inst Cardiovasc & Med Sci, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland. [Lev, Michael H.; Wu, Ona; Yoo, Albert J.; Copen, William A.; Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Liebeskind, David S.; Alger, Jeffry R.; Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Stroke Ctr, Los Angeles, CA 90024 USA. [Luby, Marie; Latour, Lawrence L.] NINDS, Stroke Diagnost & Therapeut Sect, Bethesda, MD 20892 USA. [Luby, Marie; Latour, Lawrence L.] NIH, Bethesda, MD 20892 USA. [Muir, Keith W.] Univ Glasgow, So Gen Hosp, Dept Neurol, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland. [Parsons, Mark W.] Univ Newcastle, Hunter Med Res Inst, John Hunter Hosp, Dept Neurol, Callaghan, NSW 2308, Australia. [von Kummer, Ruediger] Tech Univ Dresden, Dept Neuroradiol, D-01062 Dresden, Germany. [von Kummer, Ruediger] Tech Univ Dresden, Dresden Univ, Stroke Ctr, Univ Hosp Carl Gustav Carus, D-01062 Dresden, Germany. [Wardlaw, Joanna M.; Carpenter, Trevor C.] Univ Edinburgh, Dept Clin Neurosci, Brain Res Imaging Ctr, Div Neuroimaging Sci,Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [Alexandrov, Andrei V.] Univ Alabama Hosp & Clin, Comprehens Stroke Ctr, Dept Neurol, Birmingham, AL USA. [Aviv, Richard I.] Univ Toronto, Dept Med Imaging, Toronto, ON, Canada. [Aviv, Richard I.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Baron, Jean-Claude] Sorbonne Paris Cite, INSERM, U894, Paris, France. [Baron, Jean-Claude] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 1TN, England. [Calamante, Fernando; Donnan, Geoffrey A.] Florey Inst Neurosci & Mental Hlth, Dept Med, Melbourne, Vic, Australia. [Campbell, Bruce C. V.; Davis, Stephen M.] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Med, Parkville, Vic, Australia. [Campbell, Bruce C. V.; Davis, Stephen M.] Univ Melbourne, Royal Melbourne Hosp, Melbourne Brain Ctr, Dept Neurol, Parkville, Vic, Australia. [Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Kudo, Kohsuke] Hokkaido Univ Hosp, Dept Diagnost Radiol, Sapporo, Hokkaido 060, Japan. [Lee, Ting-Yim] Univ Western Ontario, Dept Med Imaging, London, ON, Canada. [Leigh, Richard] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Lin, Weili] Univ N Carolina, Biomed Res Imaging Ctr, Chapel Hill, NC USA. [Lin, Weili] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. [Lin, Weili] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. [Lyden, Patrick] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA. [Mair, Grant] Western Gen Hosp, Dept Neuroradiol, Div Neuroimaging Sci, Edinburgh EH4 2XU, Midlothian, Scotland. [Michel, Patrik] Univ Lausanne, CHU Vaudois, Dept Neurol, Lausanne, Switzerland. [Mikulik, Robert] St Annes Hosp, Int Clin Res Ctr, Dept Neurol, Brno, Czech Republic. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurol, Marcus Stroke & Neurosci Ctr,Grady Mem Hosp, Atlanta, GA 30322 USA. [Ostergaard, Leif] Aarhus Univ Hosp, Dept Neurol, Ctr Funct Integrat Neurosci, DK-8000 Aarhus, Denmark. [Pedraza, Salvador] Univ Hosp Dr Josep Trueta, IDIBGI, IDI, Dept Radiol, Girona, Spain. [Riedel, Christian H.] Univ Kiel, Dept Neuroradiol, Kiel, Germany. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Sanelli, Pina C.] NewYork Presbyterian Hosp, Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Sasaki, Makoto] Iwate Med Univ, Inst Biomed Sci, Dept Radiol, Yahaba, Iwate, Japan. [Schellinger, Peter D.] Johannes Wesling Klinikum Minden, Dept Neurol, Minden, Germany. [Tsivgoulis, Georgios] Univ Alabama Birmingham, Dept Neurol, Comprehens Stroke Ctr, Birmingham, AL 35294 USA. [Tsivgoulis, Georgios] Univ Athens, Sch Med, Dept Neurol 2, GR-11527 Athens, Greece. [Wechsler, Lawrence R.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [White, Philip M.] Newcastle Univ, Inst Ageing & Hlth, Dept Neuroradiol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Zaidat, Osama O.] Froedtert Hosp, Milwaukee, WI USA. [Furlan, Anthony J.] Case Western Reserve Univ, Dept Neurol, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany. [Kang, Dong-Wha] Univ Ulsan, Dept Neurol, Asan Med Ctr, Coll Med, Seoul, South Korea. [Kidwell, Chelsea] Georgetown Univ, Dept Neurol, Washington, DC USA. [Kidwell, Chelsea] Georgetown Univ, Stroke Ctr, Washington, DC USA. [Thijs, Vincent N.] Catholic Univ Louvain VIB, Neurobiol Lab, Vesalius Res Ctr, B-3000 Louvain, Belgium. [Thijs, Vincent N.] Catholic Univ Louvain VIB, Leuven Res Inst Neurosci & Dis, B-3000 Louvain, Belgium. [Thijs, Vincent N.] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium. [Warach, Steven J.] Seton UT SW Clin Res Inst Austin, Austin, TX USA. [Warach, Steven J.] UT Southwestern Med Ctr, Dept Neurol & Neurotherapeut, Austin, TX USA. [Wintermark, Max] Univ Virginia, Dept Radiol, Div Neuroradiol, Charlottesville, VA USA. RP Wintermark, M (reprint author), UVA, Dept Radiol, Div Neuroradiol, Charlottesville, VA USA. EM Max.Wintermark@gmail.com RI Michel, Patrik/Q-2275-2016; Lee, Ting-Yim/M-1721-2013; Parsons, Mark/G-3750-2014; Davis, Stephen/L-5260-2013; Demchuk, Andrew/E-1103-2012; Thijs, Vincent/C-3647-2009; Muir, Keith/A-7670-2011; Ostergaard, Leif/A-9281-2008; OI Michel, Patrik/0000-0003-4954-7579; Davis, Stephen/0000-0003-0962-2300; Leigh, Richard/0000-0002-8285-1815; Alexandrov, Andrei V/0000-0001-8871-1023; Saver, Jeffrey/0000-0001-9141-2251; Wintermark, Max/0000-0002-6726-3951; Demchuk, Andrew/0000-0002-4930-7789; Thijs, Vincent/0000-0002-6614-8417; Muir, Keith/0000-0001-9535-022X; Ostergaard, Leif/0000-0003-2930-6997; Fiebach, Jochen B./0000-0002-7936-6958; Campbell, Bruce/0000-0003-3632-9433; Derdeyn, Colin/0000-0002-5932-2683; Donnan, Geoffrey/0000-0001-6324-3403; baron, jean-claude/0000-0002-5264-2588 FU Bayer; GE Healthcare; Philips Healthcare; Siemens Healthcare; Bracco; Toshiba; Vital Images FX Stroke Imaging Research (STIR) efforts were supported by generous grants from Bayer, GE Healthcare, Philips Healthcare, Siemens Healthcare, Bracco, Toshiba, and Vital Images. NR 79 TC 62 Z9 63 U1 2 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2013 VL 44 IS 9 BP 2628 EP 2639 DI 10.1161/STROKEAHA.113.002015 PG 12 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 293OP UT WOS:000329982500063 PM 23860298 ER PT J AU Hosain, GMM Latini, DM Kauth, MR Goltz, HH Helmer, DA AF Hosain, G. M. Monawar Latini, David M. Kauth, Michael R. Goltz, Heather Honore Helmer, Drew A. TI Racial Differences in Sexual Dysfunction Among Postdeployed Iraq and Afghanistan Veterans SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE race; ethnicity; sexual dysfunction; postdeployment; veterans ID POSTTRAUMATIC-STRESS-DISORDER; ERECTILE DYSFUNCTION; CARDIOVASCULAR-DISEASE; UNITED-STATES; RISK-FACTORS; PREVALENCE; MEN; SYMPTOMS; HEALTH; SATISFACTION AB This study examined the racial/ethnic differences in prevalence and risk factors of sexual dysfunction among postdeployed Iraqi/Afghanistan veterans. A total of 3,962 recently deployed veterans were recruited from Houston Veterans Affairs medical center. The authors examined sociodemographic, medical, mental-health, and lifestyle-related variables. Sexual dysfunction was diagnosed by ICD9-CM code and/or medicines prescribed for sexual dysfunction. Analyses included chi-square, analysis of variance, and multivariate logistic regression. Sexual dysfunction was observed 4.7% in Whites, 7.9% in African Americans, and 6.3% in Hispanics. Age, marital status, smoking, and hypertension were risk factors for Whites, whereas age, marital status, posttraumatic stress disorder and hypertension were significant for African Americans. For Hispanics, only age and posttraumatic stress disorder were significant. This study identified that risk factors of sexual dysfunction varied by race/ethnicity. All postdeployed veterans should be screened; and psychosocial support and educational materials should address race/ethnicity-specific risk factors. C1 [Hosain, G. M. Monawar; Latini, David M.; Kauth, Michael R.; Goltz, Heather Honore] Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Hosain, G. M. Monawar; Latini, David M.; Kauth, Michael R.; Goltz, Heather Honore] Baylor Coll Med, Houston, TX 77030 USA. [Kauth, Michael R.] VA South Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Goltz, Heather Honore] Univ Houston Downtown, Houston, TX USA. [Helmer, Drew A.] VA RRD Ctr Excellence & PrimeCare, Houston, TX USA. [Helmer, Drew A.] VA New Jersey Hlth Care Serv, E Orange, NJ USA. [Helmer, Drew A.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. RP Hosain, GMM (reprint author), Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM monawarhosain@gmail.com OI Latini, David/0000-0002-6161-4861 FU NIDDK NIH HHS [K12 DK0083014, K12 DK083014] NR 31 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 1557-9883 EI 1557-9891 J9 AM J MENS HEALTH JI Am. J. Mens Health PD SEP PY 2013 VL 7 IS 5 BP 374 EP 381 DI 10.1177/1557988312471842 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 287WY UT WOS:000329574200003 PM 23300201 ER PT J AU El Ouaamari, A Zhou, JY Dirice, E Liew, C Kim, JS Smith, R Qian, WJ Kulkarni, R AF El Ouaamari, A. Zhou, J-Y Dirice, E. Liew, C. Kim, J-S Smith, R. Qian, W-J Kulkarni, R. TI Mechanisms underlying compensatory islet response to insulin resistance SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [El Ouaamari, A.; Dirice, E.; Liew, C.; Kulkarni, R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Zhou, J-Y; Kim, J-S; Smith, R.; Qian, W-J] Pacific NW Natl Lab, Richland, WA 99352 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 541 BP S223 EP S223 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196901199 ER PT J AU Jacobson, AM Braffett, BH Cleary, PA Dunn, RL Larkin, ME Wessels, H Sarma, AV AF Jacobson, A. M. Braffett, B. H. Cleary, P. A. Dunn, R. L. Larkin, M. E. Wessels, H. Sarma, A. V. CA DCCT EDIC Res Grp TI Urologic complications and health-related quality of life in type 1 diabetes: long-term follow-up in the DCCT/EDIC study SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Jacobson, A. M.] Winthrop Univ Hosp, Diabet Obes & Cardiometab Res Ctr, Mineola, NY 11501 USA. [Braffett, B. H.; Cleary, P. A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Dunn, R. L.; Sarma, A. V.] Univ Michigan, Ann Arbor, MI 48109 USA. [Larkin, M. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wessels, H.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 1316 BP S525 EP S525 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196902514 ER PT J AU Kashyap, SR Schauer, P Bhatt, DL Gupta, M Wolski, K Pothier, C Kirwan, J Brethauer, S Kennedy, L AF Kashyap, S. R. Schauer, P. Bhatt, D. L. Gupta, M. Wolski, K. Pothier, C. Kirwan, J. Brethauer, S. Kennedy, L. TI Increased free testosterone levels following bariatric surgery are related to weight loss and glycaemic control in men with type 2 diabetes: analysis from a RCT SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Kashyap, S. R.; Gupta, M.; Kennedy, L.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Schauer, P.; Brethauer, S.] Cleveland Clin Fdn, Bariatr & Metab Inst, Cleveland, OH 44195 USA. [Bhatt, D. L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Wolski, K.; Pothier, C.] Cleveland Clin Fdn, Inst Heart & Vasc, Cleveland, OH 44195 USA. [Kirwan, J.] Cleveland Clin Fdn, Lerner Inst, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 714 BP S288 EP S288 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196901371 ER PT J AU Laffel, L Chase, P Bailey, T Buckingham, B Liljenquist, D Daniels, M Nakamura, K AF Laffel, L. Chase, P. Bailey, T. Buckingham, B. Liljenquist, D. Daniels, M. Nakamura, K. TI Performance of a new continuous glucose monitoring (CGM) system in youth with diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Laffel, L.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Chase, P.] Barbara Davis Ctr Diabet, Pediat Sect, Aurora, CO USA. [Bailey, T.] Adv Metab Care & Res Inst, Escondido, CA USA. Stanford, Pediat, Palo Alto, CA USA. [Liljenquist, D.] Rocky Mt Diabet & Osteoporosis Ctr, Idaho Falls, ID USA. [Daniels, M.] Childrens Hosp Orange Cty, Orange, CA USA. [Nakamura, K.] Dexcom, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 1094 BP S440 EP S440 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196902291 ER PT J AU Li, L Sun, Z Yang, J Waldron, RT Lugea, A Pandol, SJ AF Li, L. Sun, Z. Yang, J. Waldron, R. T. Lugea, A. Pandol, S. J. TI Hyperglycaemia and hyperinsulinaemia promote fibrogenesis: increased risk of pancreatic cancer SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Li, L.; Sun, Z.; Yang, J.] Southeast Univ, Zhongda Hosp, Nanjing, Jiangsu, Peoples R China. [Li, L.; Waldron, R. T.; Lugea, A.; Pandol, S. J.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Waldron, R. T.; Pandol, S. J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 803 BP S321 EP S321 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196901460 ER PT J AU Lundh, M Galbo, T Wagner, FF Christensen, DP Walpita, D Gale, JP Zhang, YL Hooker, JM Shulman, GI Mandrup-Poulsen, T Holson, EB Wagner, BK AF Lundh, M. Galbo, T. Wagner, F. F. Christensen, D. P. Walpita, D. Gale, J. P. Zhang, Y-L Hooker, J. M. Shulman, G. I. Mandrup-Poulsen, T. Holson, E. B. Wagner, B. K. TI HDAC3 inhibition rescues pancreatic beta cells from glucolipotoxicity and improves insulin secretion in obese diabetic rats SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Lundh, M.; Christensen, D. P.; Mandrup-Poulsen, T.] Univ Copenhagen, Dept Biomed Sci, DK-1168 Copenhagen, Denmark. [Lundh, M.; Walpita, D.; Wagner, B. K.] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA USA. [Galbo, T.; Shulman, G. I.] Yale Univ, Dept Internal Med, New Haven, CT USA. [Wagner, F. F.; Gale, J. P.; Zhang, Y-L; Holson, E. B.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Hooker, J. M.] Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA USA. [Mandrup-Poulsen, T.] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 529 BP S219 EP S219 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196901187 ER PT J AU Marullo, L Voight, B Fuchsberger, C Scapoli, C Dupuis, J Meigs, JB Morris, AP Prokopenko, I AF Marullo, L. Voight, B. Fuchsberger, C. Scapoli, C. Dupuis, J. Meigs, J. B. Morris, A. P. Prokopenko, I. TI Dissecting the pleiotropic effects of established type 2 diabetes and other cardiometabolic trait loci to define pathways and gene networks involved in type 2 diabetes pathogenesis SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Marullo, L.; Scapoli, C.] Univ Ferrara, Dept Life Sci & Biotechnol, Genet Sect, I-44100 Ferrara, Italy. [Marullo, L.; Morris, A. P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Voight, B.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. [Voight, B.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Fuchsberger, C.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Dupuis, J.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Prokopenko, I.] Imperial Coll London, Dept Genom Common Dis, London, England. RI Scapoli, Chiara/E-2268-2015 OI Scapoli, Chiara/0000-0003-4058-4787 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 374 BP S158 EP S159 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196901033 ER PT J AU Marx, N Rosenstock, J Kahn, SE Zinman, B Kastelein, JJ Lachin, J Espeland, MA Bluhmki, E Mattheus, M Patel, S Johansen, O Woerle, HJ AF Marx, N. Rosenstock, J. Kahn, S. E. Zinman, B. Kastelein, J. J. Lachin, J. Espeland, M. A. Bluhmki, E. Mattheus, M. Patel, S. Johansen, O. Woerle, H. -J. TI Baseline characteristics of participants enrolled in the cardiovascular outcome study of linagliptin versus glimepiride in early type 2 diabetes (CAROLINA) SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Marx, N.] Univ Hosp Aachen, Dept Internal Med 1, Aachen, Germany. [Rosenstock, J.] Dallas Diabet & Endocrine Ctr, Dallas, TX USA. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Dept Med, Seattle, WA USA. [Zinman, B.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Zinman, B.] Univ Toronto, Div Endocrinol, Toronto, ON M5S 1A1, Canada. [Kastelein, J. J.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Lachin, J.] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Espeland, M. A.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Bluhmki, E.] Boehringer Ingelheim GmbH & Co KG, Biberach, Germany. [Mattheus, M.; Johansen, O.; Woerle, H. -J.] Boehringer Ingelheim KG, Ingelheim, Germany. [Patel, S.] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 73 BP S36 EP S37 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196900074 ER PT J AU Mezza, T Muscogiuri, G Sorice, G Clemente, G Giaccari, A Kulkarni, RN AF Mezza, T. Muscogiuri, G. Sorice, G. Clemente, G. Giaccari, A. Kulkarni, R. N. TI Effects of altered insulin sensitivity on islet morphology in humans SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Mezza, T.; Kulkarni, R. N.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Mezza, T.; Muscogiuri, G.; Sorice, G.; Clemente, G.; Giaccari, A.] Univ Cattolica Sacro Cuore, I-00168 Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 512 BP S213 EP S213 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196901170 ER PT J AU Newswanger, B Prestrelski, S Scott, N Damiano, ER Jiang, J El-Khatib, FH McKeon, KM Russell, SJ Sluss, P AF Newswanger, B. Prestrelski, S. Scott, N. Damiano, E. R. Jiang, J. El-Khatib, F. H. McKeon, K. M. Russell, S. J. Sluss, P. TI Pharmacokinetics and pharmacodynamics of a chemically stable micro-dosed glucagon in a diabetic swine model of type 1 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Newswanger, B.; Prestrelski, S.; Scott, N.] Xeris Pharmaceut, Austin, TX USA. [Damiano, E. R.; Jiang, J.; El-Khatib, F. H.; McKeon, K. M.] Boston Univ, Boston, MA 02215 USA. [Russell, S. J.; Sluss, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 596 BP S244 EP S244 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196901254 ER PT J AU Njolstad, PR Chudasama, KK Winney, J Johansson, S Claudi, T Koenig, R Haldorsen, I Johansson, B Woo, JR Aarskog, D Sagen, JV Kahn, C Molven, A AF Njolstad, P. R. Chudasama, K. K. Winney, J. Johansson, S. Claudi, T. Koenig, R. Haldorsen, I. Johansson, B. Woo, J. R. Aarskog, D. Sagen, J. V. Kahn, C. Molven, A. TI SHORT syndrome with partial lipodystrophy due to impaired PI 3-kinase signalling SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Njolstad, P. R.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Chudasama, K. K.; Johansson, S.; Johansson, B.; Aarskog, D.] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway. [Winney, J.; Woo, J. R.; Kahn, C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Claudi, T.] Nordlandssykehuset, Dept Med, Bodo, Norway. [Koenig, R.] Goethe Univ Frankfurt, Dept Human Genet, Frankfurt, Germany. [Haldorsen, I.; Sagen, J. V.; Molven, A.] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 33 BP S20 EP S20 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196900034 ER PT J AU Nowak, N Skupien, J Szopa, M Solecka, I Malecki, M AF Nowak, N. Skupien, J. Szopa, M. Solecka, I. Malecki, M. TI Assessment of serum ghrelin as a biomarker of HNF1A-MODY SO DIABETOLOGIA LA English DT Meeting Abstract CT 49th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 23-27, 2013 CL Barcelona, SPAIN SP European Assoc Study Diabet C1 [Nowak, N.; Skupien, J.; Szopa, M.; Solecka, I.; Malecki, M.] Jagiellonian Univ, Dept Metab Dis, Krakow, Poland. [Nowak, N.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2013 VL 56 SU 1 MA 18 BP S14 EP S14 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 282TQ UT WOS:000329196900019 ER PT J AU Nguyen, DD Muthupalani, S Goettel, JA Eston, MA Mobley, M Taylor, NS McCabe, A Marin, R Snapper, SB Fox, JG AF Nguyen, Deanna D. Muthupalani, Suresh Goettel, Jeremy A. Eston, Michelle A. Mobley, Melissa Taylor, Nancy S. McCabe, Amanda Marin, Romela Snapper, Scott B. Fox, James G. TI Colitis and Colon Cancer in WASP-Deficient Mice Require Helicobacter Species SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Helicobacter species; colitis; animal models; inflammatory bowel disease; Wiskott-Aldrich syndrome protein ID WISKOTT-ALDRICH-SYNDROME; INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; SYNDROME PROTEIN; HEPATICUS INFECTION; SCID MICE; SP-NOV; BILIS; MODELS; MULTIPLE AB Background:Wiskott-Aldrich syndrome protein-deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which Helicobacter spp. have been implicated in disease pathogenesis. We sought to determine the role of Helicobacter spp. in colitis development in Wiskott-Aldrich syndrome protein-deficient (WKO) mice.Methods:Feces from WKO mice raised under specific pathogen-free conditions were evaluated for the presence of Helicobacter spp., after which a subset of mice were rederived in Helicobacter spp.-free conditions. Helicobacter spp.-free WKO animals were subsequently infected with Helicobacter bilis.Results:Helicobacter spp. were detected in feces from WKO mice. After rederivation in Helicobacter spp.-free conditions, WKO mice did not develop spontaneous colitis but were susceptible to radiation-induced colitis. Moreover, a T-cell transfer model of colitis dependent on Wiskott-Aldrich syndrome protein-deficient innate immune cells also required Helicobacter spp. colonization. Helicobacter bilis infection of rederived WKO mice led to typhlitis and colitis. Most notably, several H. bilis-infected animals developed dysplasia with 10% demonstrating colon carcinoma, which was not observed in uninfected controls.Conclusions:Spontaneous and T-cell transfer, but not radiation-induced, colitis in WKO mice is dependent on the presence of Helicobacter spp. Furthermore, H. bilis infection is sufficient to induce typhlocolitis and colon cancer in Helicobacter spp.-free WKO mice. This animal model of a human immunodeficiency with chronic colitis and increased risk of colon cancer parallels what is seen in human colitis and implicates specific microbial constituents in promoting immune dysregulation in the intestinal mucosa. C1 [Nguyen, Deanna D.; Eston, Michelle A.; Marin, Romela] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Nguyen, Deanna D.; Eston, Michelle A.; Marin, Romela] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Nguyen, Deanna D.; Goettel, Jeremy A.; Eston, Michelle A.; Snapper, Scott B.] Harvard Univ, Sch Med, Boston, MA USA. [Muthupalani, Suresh; Mobley, Melissa; Taylor, Nancy S.; McCabe, Amanda; Fox, James G.] MIT, Div Comparat Med, Boston, MA USA. [Goettel, Jeremy A.; Snapper, Scott B.] Boston Childrens Hosp, Dept Gastroenterol Nutr, Boston, MA 02115 USA. [Snapper, Scott B.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Snapper, SB (reprint author), Boston Childrens Hosp, Dept Gastroenterol Nutr, 300 Longwood Ave, Boston, MA 02115 USA. EM scott.snapper@childrens.harvard.edu; jgfox@MIT.edu FU National Institutes of Health [K08DK083430, R01AI50950, P01 HL059561, P30 DK34854, R01OD011141, R01CA067529, P01CA026731, P30ES02109]; Crohn's and Colitis Foundation of America Career Development Award [2193] FX Supported by the National Institutes of Health (K08DK083430 to D.D.N.; R01AI50950, P01 HL059561, and P30 DK34854 to S. B. S.; and R01OD011141, R01CA067529, P01CA026731, and P30ES02109 to J.G.F.) and Crohn's and Colitis Foundation of America Career Development Award 2193 (to D.D.N.). NR 49 TC 9 Z9 9 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2013 VL 19 IS 10 BP 2041 EP 2050 DI 10.1097/MIB.0b013e318295fd8f PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284WZ UT WOS:000329354000006 PM 23820270 ER PT J AU Eknoyan, D Hurley, RA Taber, KH AF Eknoyan, Donald Hurley, Robin A. Taber, Katherine H. TI The Neurobiology of Placebo and Nocebo: How Expectations Influence Treatment Outcomes SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID PARKINSONS-DISEASE; DOPAMINE RELEASE; SPINAL-CORD; ANALGESIA; PAIN; RESPONSES; SYSTEM; ACTIVATION; MECHANISMS; BRAIN C1 [Eknoyan, Donald] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Eknoyan, Donald] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Hurley, Robin A.] Vet Affairs Mid Atlantic Mental Illness Res Educ, Durham, NC 27701 USA. [Hurley, Robin A.] WG Hefner Vet Affairs Med Ctr Salisbury, Salisbury, NC USA. [Hurley, Robin A.] Wake Forest Sch Med Winston Salem, Dept Psychiat, Winston Salem, NC USA. [Hurley, Robin A.] Wake Forest Sch Med Winston Salem, Dept Radiol, Winston Salem, NC USA. [Hurley, Robin A.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Taber, Katherine H.] Via Coll Osteopath Med Blacksburg, Div Biomed Sci, Blacksburg, VA USA. [Taber, Katherine H.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Hurley, RA (reprint author), Vet Affairs Mid Atlantic Mental Illness Res Educ, Durham, NC 27701 USA. EM Robin.Hurley@va.gov NR 38 TC 0 Z9 0 U1 1 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2013 VL 25 IS 4 BP 250 EP 254 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 286TN UT WOS:000329491700001 ER PT J AU Marshall, GA Donovan, NJ Lorius, N Gidicsin, CM Maye, J Pepin, LC Becker, JA Amariglio, RE Rentz, DM Sperling, RA Johnson, KA AF Marshall, Gad A. Donovan, Nancy J. Lorius, Natacha Gidicsin, Christopher M. Maye, Jacqueline Pepin, Lesley C. Becker, J. Alex Amariglio, Rebecca E. Rentz, Dorene M. Sperling, Reisa A. Johnson, Keith A. TI Apathy Is Associated With Increased Amyloid Burden in Mild Cognitive Impairment SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC INVENTORY; INSTRUMENTAL ACTIVITIES; EXECUTIVE FUNCTION; DEMENTIA; DEPOSITION; BRAIN; PSYCHOPATHOLOGY; DEPRESSION AB Apathy is the most common neuropsychiatric symptom in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. The authors sought to determine whether apathy is associated with cortical amyloid burden, as measured by Pittsburgh Compound B (PiB) positron emission tomography (PET), and regional hypometabolism, measured by 18F-fluorodeoxyglocuse (FDG) PET in MCI. The authors found a significant association between increased apathy (lower Apathy Evaluation Scale score) and greater cortical PiB retention independent of age, but no significant association between apathy and regional FDG metabolism. These results suggest that increased apathy is associated with greater amyloid burden but not regional hypometabolism in MCI. C1 [Marshall, Gad A.; Lorius, Natacha; Amariglio, Rebecca E.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Ctr Alzheimer Res & Treatment, Brigham & Womens Hosp, Boston, MA 02115 USA. [Marshall, Gad A.; Lorius, Natacha; Amariglio, Rebecca E.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Lorius, Natacha; Amariglio, Rebecca E.; Rentz, Dorene M.] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Harvard Univ, Sch Med, Ctr Alzheimer Res & Treatment, Brigham & Womens Hosp, Boston, MA 02115 USA. EM gamarshall@partners.org FU Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694]; Janssen Alzheimer Immunotherapy; Wyeth/Pfizer Pharmaceuticals; Bristol-Myers-Squibb; [R01 AG027435]; [K23 AG033634]; [K24 AG035007] FX This study was supported by R01 AG027435, K23 AG033634, K24 AG035007, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), and the Harvard Aging Brain Study (P01 AGO36694).; Authors have also received research salary support from Janssen Alzheimer Immunotherapy (DMR, GAM, REA), Wyeth/Pfizer Pharmaceuticals (DMR, GAM, REA), and Bristol-Myers-Squibb (RAS). NR 40 TC 13 Z9 14 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2013 VL 25 IS 4 BP 302 EP 307 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 286TN UT WOS:000329491700038 PM 24247857 ER PT J AU Avidan, A Hays, RD Diaz, N Bordelon, Y Thompson, AW Vassar, SD Vickrey, BG AF Avidan, Alon Hays, Ron D. Diaz, Natalie Bordelon, Yvette Thompson, Alexander W. Vassar, Stefanie D. Vickrey, Barbara G. TI Associations of Sleep Disturbance Symptoms With Health-Related Quality of Life in Parkinson's Disease SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MEDICAL OUTCOMES; DISORDERS; DEPRESSION; SCALE; RECOMMENDATIONS; RESPIRATION; PROGRESSION; INSOMNIA; ONSET AB The authors examined associations of various sleep-disturbance symptoms with health-related quality of life (HRQOL) in 153 adults with Parkinson's disease (PD). PD patients reported more snoring, sleep inadequacy, daytime somnolence, and sleep-maintenance problems than the general population. Symptoms having the broadest and strongest unique associations with generic HRQOL (eight scales; two composites of SF-36) were daytime somnolence (five scales; one composite), sleep initiation (eight scales; two composites), and awakening short of breath or with headache (six scales; two composites). Associations of selected sleep-disturbance symptoms-some unanticipated-suggest that assessing specific symptoms is worthwhile in clinical care. C1 [Avidan, Alon] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. Harbor UCLA, Dept Neurol, Los Angeles, CA USA. Behav Hlth Serv, Grp Hlth Cooperat, Seattle, WA USA. Parkinsons Dis Res Educ & Clin Ctr, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Avidan, A (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. EM avidan@mednet.ucla.edu FU Parkinson Alliance; National Institute of Neurological Disorders and Stroke [NS038367]; Veteran's Administration; National Institute of Aging [P30AG021684]; National Center on Minority Health and Health Disparities [P20MD000182] FX Study support was provided by the Parkinson Alliance, by National Institute of Neurological Disorders and Stroke NS038367, and by the Veteran's Administration. Dr. Hays was supported in part by a National Institute of Aging (P30AG021684) and National Center on Minority Health and Health Disparities (P20MD000182) grants. NR 41 TC 3 Z9 3 U1 0 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2013 VL 25 IS 4 BP 319 EP 326 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 286TN UT WOS:000329491700040 PM 24247858 ER PT J AU Boca, SM Bravo, HC Caffo, B Leek, JT Parmigiani, G AF Boca, Simina M. Bravo, Hector Ceorrada Caffo, Brian Leek, Jeffrey T. Parmigiani, Giovanni TI A Decision-Theory Approach to Interpretable Set Analysis for High-Dimensional Data SO BIOMETRICS LA English DT Article DE Atomic false discovery rate; Gene-sets; Hypothesis testing; Set-level inference ID FALSE DISCOVERY RATE; GENE-EXPRESSION; ENRICHMENT ANALYSIS; MICROARRAY DATA; EXTENSIONS; TESTS; RATES; FMRI AB A key problem in high-dimensional significance analysis is to find pre-defined sets that show enrichment for a statistical signal of interest; the classic example is the enrichment of gene sets for differentially expressed genes. Here, we propose a new decision-theory approach to the analysis of gene sets which focuses on estimating the fraction of non-null variables in a set. We introduce the idea of atoms, non-overlapping sets based on the original pre-defined set annotations. Our approach focuses on finding the union of atoms that minimizes a weighted average of the number of false discoveries and missed discoveries. We introduce a new false discovery rate for sets, called the atomic false discovery rate (afdr), and prove that the optimal estimator in our decision-theory framework is to threshold the afdr. These results provide a coherent and interpretable framework for the analysis of sets that addresses the key issues of overlapping annotations and difficulty in interpreting p values in both competitive and self-contained tests. We illustrate our method and compare it to a popular existing method using simulated examples, as well as gene-set and brain ROI data analyses. C1 [Boca, Simina M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bravo, Hector Ceorrada] Univ Maryland, College Pk, MD 20742 USA. [Caffo, Brian; Leek, Jeffrey T.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Boca, SM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM jleek@jhsph.edu OI Leek, Jeffrey/0000-0002-2873-2671; Corrada Bravo, Hector/0000-0002-1255-4444 FU NIH [3T32GM074906-04S1]; Johns Hopkins Sommer Scholar Program; Intramural Program of the NIH FX We would like to thank Rafael Irizarry, Luigi Marchionni, and John Storey for helpful discussions and sharing of code and data, as well as the referee and editors for their constructive comments. This research was supported by the NIH grant 3T32GM074906-04S1, the Johns Hopkins Sommer Scholar Program, and the Intramural Program of the NIH. NR 37 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2013 VL 69 IS 3 BP 614 EP 623 DI 10.1111/biom.12060 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 283ZO UT WOS:000329285700009 PM 23909925 ER PT J AU Phillips, JJ Aranda, D Ellison, DW Judkins, AR Croul, SE Brat, DJ Ligon, KL Horbinski, C Venneti, S Zadeh, G Santi, M Zhou, SM Appin, CL Sioletic, S Sullivan, LM Martinez-Lage, M Robinson, AE Yong, WH Cloughesy, T Lai, A Phillips, HS Marshall, R Mueller, S Haas-Kogan, DA Molinaro, AM Perry, A AF Phillips, Joanna J. Aranda, Derick Ellison, David W. Judkins, Alexander R. Croul, Sidney E. Brat, Daniel J. Ligon, Keith L. Horbinski, Craig Venneti, Sriram Zadeh, Gelareh Santi, Mariarita Zhou, Shengmei Appin, Christina L. Sioletic, Stefano Sullivan, Lisa M. Martinez-Lage, Maria Robinson, Aaron E. Yong, William H. Cloughesy, Timothy Lai, Albert Phillips, Heidi S. Marshall, Roxanne Mueller, Sabine Haas-Kogan, Daphne A. Molinaro, Annette M. Perry, Arie TI PDGFRA Amplification is Common in Pediatric and Adult High-Grade Astrocytomas and Identifies a Poor Prognostic Group in IDH1 Mutant Glioblastoma SO BRAIN PATHOLOGY LA English DT Article DE astrocytoma; FISH; IDH1; isocitrate dehydrogenase 1; PDGFRA; prognosis ID INTEGRATED GENOMIC ANALYSIS; GROWTH-FACTOR; DIFFUSE GLIOMAS; EGFR; CELL; EXPRESSION; SUBCLASSES; AUTOCRINE; MUTATIONS; RECEPTORS AB High-grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and isocitrate dehydrogenase 1 (IDH1)(R132H) mutation was a significant independent prognostic factor (P=0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs. C1 [Phillips, Joanna J.; Aranda, Derick; Marshall, Roxanne; Perry, Arie] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Phillips, Joanna J.; Aranda, Derick; Robinson, Aaron E.; Molinaro, Annette M.; Perry, Arie] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Phillips, Joanna J.; Aranda, Derick; Robinson, Aaron E.; Marshall, Roxanne; Mueller, Sabine; Haas-Kogan, Daphne A.; Molinaro, Annette M.; Perry, Arie] Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. [Mueller, Sabine] Univ Calif San Francisco, Dept Clin Neurol, San Francisco, CA 94143 USA. [Haas-Kogan, Daphne A.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. [Molinaro, Annette M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Phillips, Heidi S.] Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA. [Judkins, Alexander R.; Zhou, Shengmei] Childrens Hosp Los Angeles, Dept Pathol, Los Angeles, CA 90027 USA. [Yong, William H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Cloughesy, Timothy; Lai, Albert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Ellison, David W.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Brat, Daniel J.; Appin, Christina L.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Sioletic, Stefano] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sioletic, Stefano] Harvard Univ, Sch Med, Boston, MA USA. [Horbinski, Craig] Univ Kentucky, Dept Pathol & Lab Med, Lexington, KY USA. [Venneti, Sriram] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Santi, Mariarita; Sullivan, Lisa M.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Martinez-Lage, Maria] Univ Penn Hlth Syst, Dept Pathol & Lab Med, Philadelphia, PA USA. [Croul, Sidney E.] Univ Toronto, Toronto Western Hosp, Dept Lab Med & Pathobiol, Toronto, ON M5T 2S8, Canada. [Zadeh, Gelareh] Univ Toronto, Toronto Western Hosp, Div Neurosurg, Toronto, ON M5T 2S8, Canada. RP Perry, A (reprint author), Univ Calif San Francisco, Dept Pathol, 505 Parnassus Ave,Room M551,Box 0102, San Francisco, CA 94143 USA. EM arie.perry@ucsf.edu; arie.perry@ucsf.edu OI Perry, Arie/0000-0002-8300-7261; Sullivan, Lisa/0000-0003-0726-7149; Martinez-Lage, Maria/0000-0002-5859-7562 FU National Institutes of Health [K08 NS063456, 1U01CA168878, P01CA095616]; UCSF Brain Tumor SPORE [CA097257]; Ivy Foundation Early Phase Clinical Trials Consortium-Virtual Tissue Bank; University of California San Francisco Departments of Pathology and Neurological Surgery FX This work was supported in part by the National Institutes of Health (K08 NS063456 to JJP; 1U01CA168878 to JJP; and P01CA095616 to KLL), the UCSF Brain Tumor SPORE (CA097257), the Ivy Foundation Early Phase Clinical Trials Consortium-Virtual Tissue Bank, and funds from the University of California San Francisco Departments of Pathology and Neurological Surgery. NR 32 TC 25 Z9 25 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2013 VL 23 IS 5 BP 565 EP 573 DI 10.1111/bpa.12043 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 283XQ UT WOS:000329280700007 PM 23438035 ER PT J AU Tang, R Coopey, SB Buckley, JM Aftreth, OP Fernandez, LJ Brachtel, EF Michaelson, JS Gadd, MA Specht, MC Koerner, FC Smith, BL AF Tang, Rong Coopey, Suzanne B. Buckley, Julliette M. Aftreth, Owen P. Fernandez, Leopoldo J. Brachtel, Elena F. Michaelson, James S. Gadd, Michele A. Specht, Michelle C. Koerner, Frederick C. Smith, Barbara L. TI A Pilot Study Evaluating Shaved Cavity Margins with Micro-Computed Tomography: A Novel Method for Predicting Lumpectomy Margin Status Intraoperatively SO BREAST JOURNAL LA English DT Article DE intraoperative; micro-CT; shaved cavity margin ID BREAST-CONSERVING SURGERY; FROZEN-SECTION ANALYSIS; CARCINOMA IN-SITU; 20-YEAR FOLLOW-UP; RE-EXCISION; CONSERVATION THERAPY; POSITIVE MARGINS; SURGICAL MARGINS; CANCER PATIENTS; TIME AB Microscopically clear lumpectomy margins are essential in breast conservation, as involved margins increase local recurrence. Currently, 18-50% of lumpectomies have close or positive margins that require re-excision. We assessed the ability of micro-computed tomography (micro-CT) to evaluate lumpectomy shaved cavity margins (SCM) intraoperatively to determine if this technology could rapidly identify margin involvement by tumor and reduce re-excision rates. Twenty-five SCM from six lumpectomies were evaluated with a Skyscan 1173 table top micro-CT scanner (Skyscan, Belgium). Micro-CT results were compared to histopathological results. We scanned three SCM at once with a 7-minute scanning protocol, and studied a total of 25 SCM from six lumpectomies. Images of the SCM were evaluated for radiographic signs of breast cancer including clustered microcalcifications and spiculated masses. SCM were negative by micro-CT in 19/25 (76%) and negative (2mm) by histopathology in 19/25 (76%). Margin status by micro-CT was concordant with histopathology in 23/25 (92%). Micro-CT overestimated margin involvement in 1/25 and underestimated margin involvement in 1/25. Micro-CT had an 83.3% positive predictive value, a 94.7% negative predictive value, 83.3% sensitivity, and 94.7% specificity for evaluation of SCM. Evaluation of SCM by micro-CT is an accurate and promising method of intraoperative margin assessment in breast cancer patients. The scanning time required is short enough to permit real-time feedback to the operating surgeon, allowing immediate directed re-excision. C1 [Tang, Rong; Coopey, Suzanne B.; Buckley, Julliette M.; Aftreth, Owen P.; Fernandez, Leopoldo J.; Michaelson, James S.; Gadd, Michele A.; Specht, Michelle C.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Tang, Rong] Cent S Univ, Hunan Prov Tumor Hosp, Div Breast Surg, Affiliated Tumor Hosp,Xiangya Med Sch, Changsha, Hunan, Peoples R China. [Brachtel, Elena F.; Michaelson, James S.; Koerner, Frederick C.] Massachusetts Gen Hosp, Dept Surg Pathol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org NR 38 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD SEP PY 2013 VL 19 IS 5 BP 485 EP 489 DI 10.1111/tbj.12146 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 283ZC UT WOS:000329284500005 PM 23773680 ER PT J AU Weiss, MJ Wolfgang, CL AF Weiss, Matthew J. Wolfgang, Christopher L. TI Irreversible electroporation: A novel pancreatic cancer therapy SO CURRENT PROBLEMS IN CANCER LA English DT Article ID TISSUE ABLATION; MANAGEMENT C1 [Weiss, Matthew J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Weiss, Matthew J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Weiss, Matthew J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weiss, Matthew J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wolfgang, Christopher L.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Weiss, MJ (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 7 TC 4 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 EI 1535-6345 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD SEP-OCT PY 2013 VL 37 IS 5 BP 262 EP 265 DI 10.1016/j.currproblcancer.2013.10.002 PG 4 WC Oncology SC Oncology GA 277CD UT WOS:000328795100003 PM 24331180 ER PT J AU Walker, RJ Smalls, BL Bonilha, HS Campbell, JA Egede, LE AF Walker, Rebekah J. Smalls, Brittany L. Bonilha, Heather Shaw Campbell, Jennifer A. Egede, Leonard E. TI BEHAVIORAL INTERVENTIONS TO IMPROVE GLYCEMIC CONTROL IN AFRICAN AMERICANS WITH TYPE 2 DIABETES: A SYSTEMATIC REVIEW SO ETHNICITY & DISEASE LA English DT Article DE Diabetes; Glucose Control; African Americans; Ethnic Groups; Lifestyle ID SELF-MANAGEMENT EDUCATION; HEALTH DISPARITIES; RACIAL-DIFFERENCES; ADULTS; OLDER; METAANALYSIS; DISEASE; IMPACT; BLACK; TRIAL AB Objective: The use of behavioral interventions has been shown to improve glycemic control, however, the effectiveness of different behavioral interventions in one of the most high risk populations, African Americans, remains unclear. Our systematic review identified and examined findings of published behavioral interventions targeted at African Americans to improve glycemic control. The goal of our study was to distinguish which interventions were effective and identify areas for future research. Design: Medline, PsychInfo, and CINAHL were searched for articles published from January 2000 through January 2012 using a reproducible strategy. Study eligibility criteria included interventions aimed at changing behavior in adult African Americans with type 2 diabetes and measured glycemic control. Results: Ten studies met the inclusion criteria, of which five showed a statistically significant change in HbA1c in the intervention group when compared to the control group. Summary information and characteristics of the reviewed studies are provided. Conclusions: Characteristics of successful interventions included using problem solving with the patient, culturally tailoring the intervention, and using a nurse educator. Limitations include the limited number of intervention studies available using glycemic control as the outcome measure. Clinical trials are needed to determine how best to tailor interventions to this largely underserved population and studies should describe details of cultural tailoring to provide information for future programs. C1 [Walker, Rebekah J.; Smalls, Brittany L.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Disparities Res, Charleston, SC 29425 USA. [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Walker, Rebekah J.; Smalls, Brittany L.; Bonilha, Heather Shaw] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Disparities Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu NR 34 TC 4 Z9 4 U1 3 U2 7 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2013 VL 23 IS 4 BP 401 EP 408 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 280HN UT WOS:000329019400002 PM 24392600 ER PT J AU Betancourt, RM Degnan, KO Long, JA AF Betancourt, Renee M. Degnan, Kathleen O. Long, Judith A. TI RACIAL DIFFERENCES IN GLUCOSE CONTROL AMONG PATIENTS WITH TYPE 2 DIABETES: A SURVEY ON DIETARY TEMPTATIONS, COPING, AND TRUST IN PHYSICIANS SO ETHNICITY & DISEASE LA English DT Article DE Disparities; Diabetes Mellitus; Glucose Control; Psychosocial Factors ID AFRICAN-AMERICAN; GLYCEMIC CONTROL; CARE; DISPARITIES; SCALE; OUTCOMES; BEHAVIORS; MORTALITY; ADHERENCE; QUALITY AB Objective: A quantitative evaluation of self-care behaviors, psychosocial stressors, and patient relationships to health care to better understand racial disparities in these domains. Research Design and Methods: A cross-sectional study of adult patients with type 2 diabetes in University of Pennsylvania Healthcare System who had a HbA1c test within one month of survey administration. The survey instrument included among other items, the Dieter's Inventory of Eating Temptations Self-Efficacy instrument (DIET-SE), the Jalowiec Coping Scale (JCS), and the Trust in Physician (TIP) scale. Results: 332 individuals completed the survey. Poor glucose control was significantly associated with Black race, lower income level, other demographic variables, non-perfect medication adherence, and poorer diet quality. It was also associated with lower self-efficacy to resist social dietary temptations, and among White patients it was associated was decreased use of a confrontive coping style. However, these factors did not explain the racial differences in glucose control between Blacks and Whites. Conclusions: Interventions aimed at dietary temptations, coping styles, or trust in physicians may not reduce racial disparities in glucose control. However, interventions that focus on dietary temptations may positively affect all diabetic patients. C1 [Betancourt, Renee M.] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Degnan, Kathleen O.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Div Gen Internal Med, Philadelphia VA Ctr Hlth Equ Res & Promot, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Betancourt, RM (reprint author), 995 Potrero Ave,Bldg 83, San Francisco, CA 94110 USA. EM betancourtr@fcm.ucsf.edu NR 33 TC 2 Z9 2 U1 1 U2 5 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2013 VL 23 IS 4 BP 409 EP 414 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 280HN UT WOS:000329019400003 PM 24392601 ER PT J AU Doherty, JE Woodard, LE Bear, AS Foster, AE Wilson, MH AF Doherty, Joseph E. Woodard, Lauren E. Bear, Adham S. Foster, Aaron E. Wilson, Matthew H. TI An adaptable system for improving transposon-based gene expression in vivo via transient transgene repression SO FASEB JOURNAL LA English DT Article DE piggyBac; inducible expression; gene transfer ID IMMUNE-RESPONSE; MAMMALIAN-CELLS; HYDRODYNAMIC INJECTION; FIREFLY LUCIFERASE; ADENOVIRAL VECTORS; THERAPY; LIVER; MICE; DELIVERY; TETRACYCLINE AB Transposons permit permanent cellular genome engineering in vivo. However, transgene expression falls rapidly postdelivery due to a variety of mechanisms, including immune responses. We hypothesized that delaying initial transgene expression would improve long-term transgene expression by using an engineered piggyBac transposon system that can regulate expression. We found that a 2-part nonviral Tet-KRAB inducible expression system repressed expression of a luciferase reporter in vitro. However, we also observed nonspecific promoter-independent repression. Thus, to achieve temporary transgene repression after gene delivery in vivo, we utilized a nonintegrating version of the repressor plasmid while the gene of interest was delivered in an integrating piggyBac transposon vector. When we delivered the luciferase transposon and repressor to immunocompetent mice by hydrodynamic injection, initial luciferase expression was repressed by 2 orders of magnitude. When luciferase expression was followed long term in vivo, we found that expression was increased >200-fold compared to mice that received only the luciferase transposon and piggyBac transposase. We found that repression of early transgene expression could prevent the priming of luciferase-specific T cells in vivo. Therefore, transient transgene repression postgene delivery is an effective strategy for inhibiting the antitransgene immune response and improving long-term expression in vivo without using immunosuppression.Doherty, J. E., Woodard, L. E., Bear, A. S., Foster, A. E., Wilson, M. H. An adaptable system for improving transposon-based gene expression in vivo via transient transgene repression. C1 [Doherty, Joseph E.; Bear, Adham S.; Foster, Aaron E.; Wilson, Matthew H.] Baylor Coll Med, Med Scientist Training Program, Houston, TX 77030 USA. [Doherty, Joseph E.; Wilson, Matthew H.] Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA. [Doherty, Joseph E.; Woodard, Lauren E.; Wilson, Matthew H.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Bear, Adham S.; Foster, Aaron E.; Wilson, Matthew H.] Baylor Coll Med, Interdept Program Translat Biol & Mol Med, Houston, TX 77030 USA. [Bear, Adham S.; Foster, Aaron E.; Wilson, Matthew H.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Wilson, Matthew H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Wilson, MH (reprint author), Baylor Coll Med, 1 Baylor Plaza,MS BCM395,ABBR R704, Houston, TX 77030 USA. EM mhwilson@bcm.edu FU U.S. National Institutes of Health (NIH) [T32GM007330]; NIH [T32DK064717, T32DK062706, T32DK060445, R01 DK093660]; U.S. Department of Veterans Affairs FX J.E.D. was supported by U.S. National Institutes of Health (NIH) Medical Scientist Training Program grant T32GM007330, and subsequently by NIH Cell and Gene Therapy Training grant T32DK064717 and the generous support of Bill and Mary Jo Robbins. L. E. W. was supported by NIH grant T32DK062706 and subsequently by NIH grant T32DK060445. M. H. W. was supported in part by a career development award from the U.S. Department of Veterans Affairs and NIH grant R01 DK093660. This work was also made possible by the generous support of Dr. and Mrs. Harold M. Selzman. NR 53 TC 3 Z9 3 U1 1 U2 9 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD SEP PY 2013 VL 27 IS 9 BP 3753 EP 3762 DI 10.1096/fj.13-232090 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 277SV UT WOS:000328840500033 PM 23752206 ER PT J AU Ioannou, GN AF Ioannou, George N. TI Chronic Hepatitis B Infection: A Global Disease Requiring Global Strategies SO HEPATOLOGY LA English DT Editorial Material ID PUBLIC-HEALTH MANAGEMENT; UNITED-STATES; VIRUS INFECTION; LIVER-CANCER; RECOMMENDATIONS; IDENTIFICATION; MODEL C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. [Ioannou, George N.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu NR 20 TC 11 Z9 11 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2013 VL 58 IS 3 BP 839 EP 843 DI 10.1002/hep.26516 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 283YX UT WOS:000329284000001 PM 23703788 ER PT J AU Shrivastava, S Petrone, J Steele, R Lauer, GM Di Bisceglie, AM Ray, RB AF Shrivastava, Shubham Petrone, Jessica Steele, Robert Lauer, Georg M. Di Bisceglie, Adrian M. Ray, Ratna B. TI Up-Regulation of Circulating miR-20a Is Correlated With Hepatitis C Virus-Mediated Liver Disease Progression SO HEPATOLOGY LA English DT Article ID MICRORNA EXPRESSION LEVELS; SERUM MICRORNAS; HEPATOCELLULAR-CARCINOMA; HUMAN HEPATOCYTES; CANCER; BIOMARKERS; INJURY; INFECTION; MIR-122; PLASMA AB Chronic hepatitis C virus (HCV) infection is one of the major causes of liver fibrosis and liver transplantation in the United States. Circulating microRNAs (miRNAs) in the blood are emerging as biomarkers for pathological conditions. In the present study we performed a systematic screening approach to identify up-regulated miRNAs in the plasma/serum of HCV-infected patients with different stages of hepatic histological disease severity. We initially screened serum samples of HCV-infected patients with fibrosis and compared them with sera of healthy volunteers using serum miRNA array profiling and identified a group of modulated miRNAs. Subsequent study demonstrated that miR-20a and miR-92a in HCV-infected fibrosis patients sera were significantly up-regulated when compared with that of healthy volunteers or non-HCV-associated liver disease. We have also observed an increase of plasma miR-20a and miR-92a in acute and chronic HCV-infected patients as compared to that of healthy volunteers. However, there was no correlation between the plasma/serum levels of any of these miRNAs with HCV viral loads. We next investigated longitudinal plasma samples from HCV-infected patients. Our results suggested that miR-20a and miR-92a remained unaltered in HCV-infected patients who progressed from acute to chronic infection. On the other hand, miR-92a expression was reduced in acute to resolved individuals. These data provide evidence that plasma/serum levels of miR-20a and miR-92a have potential as sensitive and cost-effective biomarkers for early detection of HCV infection. Conclusion: Circulating miR-20a may serve as a potential for predictive biomarker in HCV-mediated fibrosis. (Hepatology 2013;53:863-871) C1 [Shrivastava, Shubham; Petrone, Jessica; Steele, Robert; Ray, Ratna B.] St Louis Univ, Dept Pathol, St Louis, MO 63104 USA. [Lauer, Georg M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Di Bisceglie, Adrian M.; Ray, Ratna B.] St Louis Univ, Dept Internal Med, St Louis, MO 63104 USA. [Di Bisceglie, Adrian M.; Ray, Ratna B.] St Louis Univ, Ctr Liver, St Louis, MO 63104 USA. RP Ray, RB (reprint author), St Louis Univ, Dept Pathol, DRC 207,1100 South Grand Blvd, St Louis, MO 63104 USA. EM rayrb@slu.edu FU National Institutes of Health [DK081817]; Saint Louis University Liver Center Seed Grant FX Supported by research grant DK081817 from the National Institutes of Health and Saint Louis University Liver Center Seed Grant. NR 37 TC 49 Z9 50 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2013 VL 58 IS 3 BP 863 EP 871 DI 10.1002/hep.26296 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 283YX UT WOS:000329284000007 PM 23390075 ER PT J AU Ashraf, S Nitschke, K Warshow, UM Brooks, CR Kim, AY Lauer, GM Hydes, TJ Cramp, ME Alexander, G Little, AM Thimme, R Neumann-Haefelin, C Khakoo, SI AF Ashraf, Shirin Nitschke, Katja Warshow, Usama M. Brooks, Collin R. Kim, Arthur Y. Lauer, Georg M. Hydes, Theresa J. Cramp, Matthew E. Alexander, Graeme Little, Ann-Margaret Thimme, Robert Neumann-Haefelin, Christoph Khakoo, Salim I. TI Synergism of Tapasin and Human Leukocyte Antigens in Resolving Hepatitis C Virus Infection SO HEPATOLOGY LA English DT Article ID MHC CLASS-I; INJECTION-DRUG USERS; LINKAGE DISEQUILIBRIUM; APPARENT RESISTANCE; VIRAL CLEARANCE; CELL RESPONSES; HCV INFECTION; PEPTIDE; HLA; POLYMORPHISM AB CD8+ T-cell responses to hepatitis C virus (HCV) are important in generating a successful immune response and spontaneously clearing infection. Human leukocyte antigen (HLA) class I presents viral peptides to CD8+ T cells to permit detection of infected cells, and tapasin is an important component of the peptide loading complex for HLA class I. We sought to determine if tapasin polymorphisms affected the outcome of HCV infection. Patients with resolved or chronic HCV infection were genotyped for the known G/C coding polymorphism in exon 4 of the tapasin gene. In a European, but not a US, Caucasian population, the tapasin G allele was significantly associated with the outcome of HCV infection, being found in 82.5% of resolvers versus 71.3% of persistently infected individuals (P=0.02, odds ratio [OR]=1.90 95% confidence interval [CI]=1.11-3.23). This was more marked at the HLA-B locus at which heterozygosity of both tapasin and HLA-B was protective (P<0.03). Individuals with an HLA-B allele with an aspartate at residue 114 and the tapasin G allele were more likely to spontaneously resolve HCV infection (P<0.00003, OR=3.2 95% CI=1.6-6.6). Additionally, individuals with chronic HCV and the combination of an HLA-B allele with an aspartate at residue 114 and the tapasin G allele also had stronger CD8+ T-cell responses (P=0.02, OR=2.58, 95% CI-1.05-6.5). Conclusion: Tapasin alleles contribute to the outcome of HCV infection by synergizing with polymorphisms at HLA-B in a population-specific manner. This polymorphism may be relevant for peptide vaccination strategies against HCV infection. (Hepatology 2013;53:881-889) C1 [Ashraf, Shirin; Brooks, Collin R.; Hydes, Theresa J.; Khakoo, Salim I.] Univ Southampton, Fac Med, Southampton SO16 6YD, Hants, England. [Nitschke, Katja] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany. [Warshow, Usama M.; Cramp, Matthew E.] Derriford Hosp, Hepatol Res Grp, Peninsula Med Sch, Plymouth PL6 8DH, Devon, England. [Warshow, Usama M.; Cramp, Matthew E.] Derriford Hosp, Hepatol Dept, South West Liver Unit, Plymouth PL6 8DH, Devon, England. [Kim, Arthur Y.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Lauer, Georg M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Alexander, Graeme] Dept Med, Cambridge, England. [Little, Ann-Margaret] Lab Histocompatibil & Immunogenet, Glasgow, Lanark, Scotland. [Thimme, Robert; Neumann-Haefelin, Christoph] Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. RP Khakoo, SI (reprint author), Univ Southampton, Fac Med, Southampton Gen Hosp, Mailpoint 811,Level E South Acad Block,Tremona Rd, Southampton SO16 6YD, Hants, England. EM S.I.Khakoo@soton.ac.uk OI Khakoo, Salim/0000-0002-4057-9091 FU Wellcome Trust; Deutsche Forschungsgemeinschaft DFG [TH-719/3-1, NE1567/1-1]; National Institutes of Health [U19 AI0663445, R01 DA033541, U19 AI082630] FX Supported by grants from the Wellcome Trust (to S. I. K.), the Deutsche Forschungsgemeinschaft DFG (TH-719/3-1 to R. T. and NE1567/1-1 to C.N.H.) and the National Institutes of Health, grants U19 AI0663445 (to G. M. L. and A.Y.K.), R01 DA033541 (to A.Y.K.), and U19 AI082630 (to G.M.L.). NR 40 TC 10 Z9 10 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2013 VL 58 IS 3 BP 881 EP 889 DI 10.1002/hep.26415 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 283YX UT WOS:000329284000009 PM 23532923 ER PT J AU Baker, GM Selim, A Hoang, MP AF Baker, Gabrielle M. Selim, Angelica Hoang, Mai P. TI Vulvar Adnexal Lesions A 32-Year, Single-Institution Review From Massachusetts General Hospital SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID BASAL-CELL CARCINOMA; MAMMARY-LIKE GLANDS; OF-THE-LITERATURE; ADENOID CYSTIC CARCINOMA; EXTRAMAMMARY PAGETS-DISEASE; MUIR-TORRE-SYNDROME; PROGESTERONE-RECEPTOR POSITIVITY; MIXED HISTOPATHOLOGIC FEATURES; IN-SITU HYBRIDIZATION; SEBACEOUS CARCINOMA AB Context.-Because the skin and modified mucosal surfaces of the vulvar region contain dense apocrine glands and anogenital mammary-like glands, in addition to eccrine glands and folliculosebaceous units, benign as well as malignant lesions derived from these adnexal structures are, not surprisingly, found in the vulva. However, their incidence occurring in the vulva has not been reported, to our knowledge. Objective.-To determine the incidence of various vulvar adnexal lesions. Design.-We performed a retrospective review (19782010) of the cases at our institution. Results.-A total of 189 vulvar adnexal lesions were identified. Most of these lesions were benign (133 of 189; 70%), with hidradenoma papilliferum being the most common, followed by syringoma and various types of cysts. Rare cases of tubular adenoma, poroma, spiradenoma, hidradenoma, cylindroma, sebaceoma, and trichoepithelioma were identified. Malignant adnexal neoplasms comprised the remaining 30% (56 of 189) of the cases. Extramammary Paget disease was the most common (49 of 56), and 29% (14 of 49) demonstrated an invasive component. Rare cases of basal cell carcinoma, sebaceous carcinoma, apocrine carcinoma, adenoid cystic carcinoma, and spiradenocarcinoma were identified. Conclusions.-In this retrospective review, we identified several benign entities that have not been previously reported on the vulva, namely pilomatricoma, poroma, spiradenoma, and sebaceoma. Hidradenoma papilliferum and extramammary Paget disease were the most common benign and malignant adnexal neoplasms, respectively. The spectrum of various vulvar adnexal lesions appears to reflect the frequency of the underlying glandular elements. C1 [Baker, Gabrielle M.; Hoang, Mai P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Baker, Gabrielle M.; Hoang, Mai P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Selim, Angelica] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 148 TC 10 Z9 11 U1 1 U2 4 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2013 VL 137 IS 9 BP 1237 EP 1246 DI 10.5858/arpa.2012-0434-OA PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 269SA UT WOS:000328261000014 PM 23991738 ER PT J AU Nencioni, A Cea, M Montecucco, F Longo, VD Patrone, F Carella, AM Holyoake, TL Helgason, GV AF Nencioni, Alessio Cea, Michele Montecucco, Fabrizio Longo, Valter D. Patrone, Franco Carella, Angelo M. Holyoake, Tessa L. Helgason, G. Vignir TI Autophagy in blood cancers: biological role and therapeutic implications SO HAEMATOLOGICA LA English DT Review ID CHRONIC MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MANTLE CELL LYMPHOMA; POTENT ANTITUMOR-ACTIVITY; BCR-ABL; MULTIPLE-MYELOMA; STEM-CELLS; INDUCED APOPTOSIS; UP-REGULATION; PROTEASOME INHIBITORS AB Autophagy is a cell recycling process the molecular apparatus of which has been identified over the past decade. Autophagy allows cells to survive starvation and inhospitable conditions and plays a key role in numerous physiological functions, including hematopoiesis and immune responses. In hematologic malignancies, autophagy can either act as a chemo-resistance mechanism or have tumor suppressive functions, depending on the context. In addition, autophagy is involved in other important aspects of blood cancers as it promotes immune competence and anticancer immunity, and may even help enhance patient tolerance to standard treatments. Approaches exploiting autophagy, either to activate or inhibit it, could find broad application in hematologic malignancies and contribute to improved clinical outcomes. These aspects are discussed here together with a brief introduction to the molecular machinery of autophagy and to its role in blood cell physiology. C1 [Nencioni, Alessio; Cea, Michele; Montecucco, Fabrizio; Patrone, Franco] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Cea, Michele] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA. [Cea, Michele] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Montecucco, Fabrizio] Univ Hosp Geneva, Dept Internal Med, Fdn Med Res, Div Cardiol,Fac Med, CH-1211 Geneva, Switzerland. [Longo, Valter D.] Univ So Calif, Longev Inst, Los Angeles, CA USA. [Longo, Valter D.] Univ So Calif, Dept Biol Sci, Sch Gerontol, Los Angeles, CA 90089 USA. [Carella, Angelo M.] Azienda Osped Univ San Martino, Div Hematol 1, Genoa, Italy. [Holyoake, Tessa L.; Helgason, G. Vignir] Univ Glasgow, Coll Med Vet & Life Sci, Paul OGorman Leukaemia Res Ctr, Glasgow, Lanark, Scotland. RP Nencioni, A (reprint author), Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. EM alessio.nencioni@unige.it RI Montecucco, Fabrizio/K-8543-2016; Holyoake, Tessa/M-3668-2015 OI Montecucco, Fabrizio/0000-0003-0823-8729; Holyoake, Tessa/0000-0002-0608-6066 FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [6108]; European Seventh Framework Program [256986]; Ministero della Salute [GR-2008-1135635]; Compagnia di San Paolo; University of Genoa; Kay Kendall Research Council [G0900882, 61568166]; Scottish Universities Life Sciences Alliance [MSD23_G_Holyoake-Chan]; American Italian Cancer Foundation (AICF postdoctoral fellowship) FX The authors would like to thank the Associazione Italiana per la Ricerca sul Cancro (AIRC, grant code 6108, to AN), the European Seventh Framework Program (project number 256986, PANACREAS, to AN), the Ministero della Salute (GR-2008-1135635 to AN), the Compagnia di San Paolo, the University of Genoa, the Kay Kendall Research Council (G0900882, CHOICES, ISCRTN No. 61568166, to GVH and TLH), the Scottish Universities Life Sciences Alliance (MSD23_G_Holyoake-Chan, to CVH and TLH), and the American Italian Cancer Foundation (AICF postdoctoral fellowship to MC). NR 100 TC 24 Z9 26 U1 2 U2 17 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD SEP PY 2013 VL 98 IS 9 BP 1335 EP 1343 DI 10.3324/haematol.2012.079061 PG 9 WC Hematology SC Hematology GA 273NR UT WOS:000328542500014 PM 24006406 ER PT J AU Lawson, CM Daley, BJ Sams, VG Martindale, R Kudsk, KA Miller, KR AF Lawson, Christy M. Daley, Brian J. Sams, Valerie G. Martindale, Robert Kudsk, Kenneth A. Miller, Keith R. TI Factors That Impact Patient Outcome: Nutrition Assessment SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE nutrition assessment; body mass index; malnutrition; elective surgery ID TOTAL PARENTERAL-NUTRITION; ENTERAL NUTRITION; MALNUTRITION; UNDERNUTRITION; RISK AB Defining malnutrition and nutrition risk has been a topic of many papers and discussions throughout the modern literature. Multiple definitions have been proposed, ranging from simple body weight measurements to a more all-encompassing concept looking at disease-specific inflammatory states. Biochemical markers, elements of a history examination, physical examination findings, calculations, and technical tests have all been proposed to help further characterize and delineate those who might be at risk for malnutrition, translating to an increased risk of adverse outcomes after major surgery. The purpose of this paper is to summarize some of the most utilized and most reliable ways to determine nutrition status within the scope of the North American Surgical Nutrition Summit (2012) and discuss how to incorporate these methods into the way that patients are screened preoperatively for elective surgery. C1 [Lawson, Christy M.; Daley, Brian J.; Sams, Valerie G.] Univ Tennessee, Med Ctr, Dept Surg, Knoxville, TN 37920 USA. [Martindale, Robert] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Veteran Adm Surg Serv, Madison, WI USA. [Miller, Keith R.] Univ Louisville, Dept Surg, Louisville, KY 40292 USA. RP Lawson, CM (reprint author), Univ Tennessee, Med Ctr, Dept Surg, 1924 Alcoa Highway,Box U-11, Knoxville, TN 37920 USA. EM cmlawson@utmck.edu FU Nestle Healthcare Nutrition FX The publication of the supplement in which this article appears is supported by an educational grant from Nestle Healthcare Nutrition. Authors received an honorarium from the Nestle Nutrition Institute for their participation in the North American Surgical Nutrition Summit. NR 29 TC 3 Z9 4 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD SEP PY 2013 VL 37 IS 5 SU S BP 30S EP 38S DI 10.1177/0148607113499372 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 276XL UT WOS:000328782900003 PM 24009247 ER PT J AU Pierre, JF Heneghan, AF Lawson, CM Wischmeyer, PE Kozar, RA Kudsk, KA AF Pierre, Joseph F. Heneghan, Aaron F. Lawson, Christy M. Wischmeyer, Paul E. Kozar, Rosemary A. Kudsk, Kenneth A. TI Pharmaconutrition Review: Physiological Mechanisms SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Review DE immunonutrition; pharmaconutrition; immune modulation; nutrition therapy ID CRITICALLY-ILL PATIENTS; GAMMA-LINOLENIC ACID; INTENSIVE-CARE-UNIT; NITRIC-OXIDE SYNTHASE; ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; TOTAL PARENTERAL-NUTRITION; DOUBLE-BLIND TRIAL; SEVERE BURN INJURY; BACTERIAL-INFECTION RATES AB The search to improve outcomes in critically ill patients through nutrition support has steadily progressed over the past 4 decades. One current approach to this problem is the addition of specific nutrients as primary therapy to improve host defenses and improve the outcome of critically ill patients. The field is referred to as pharmaconutrition, with the hope of focusing investigations on each nutrient to understand its pharmacological effects on immune and clinical outcomes. The purpose of this review is to describe some of the known physiological mechanisms of pharmaconutrients such as glutamine, arginine, -3 fatty acids, and selenium. C1 [Pierre, Joseph F.; Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Pierre, Joseph F.; Heneghan, Aaron F.; Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Lawson, Christy M.] Univ Tennessee, Med Ctr, Dept Surg, Knoxville, TN 37920 USA. [Wischmeyer, Paul E.] Univ Colorado, Dept Anesthesiol, Denver, CO 80202 USA. [Kozar, Rosemary A.] Univ Texas Houston, Hlth Sci Ctr, Dept Surg, Houston, TX USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Nutr Sci, H4-736 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU Nestle Healthcare Nutrition FX The publication of the supplement in which this article appears is supported by an educational grant from Nestle Healthcare Nutrition. Authors received an honorarium from the Nestle Nutrition Institute for their participation in the North American Surgical Nutrition Summit. NR 225 TC 17 Z9 17 U1 2 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD SEP PY 2013 VL 37 IS 5 SU S BP 51S EP 65S DI 10.1177/0148607113493326 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 276XL UT WOS:000328782900005 PM 24009249 ER PT J AU Berker, E Kantarci, A Hasturk, H Van Dyke, TE AF Berker, Ezel Kantarci, Alpdogan Hasturk, Hatice Van Dyke, Thomas E. TI Blocking Proinflammatory Cytokine Release Modulates Peripheral Blood Mononuclear Cell Response to Porphyromonas gingivalis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Interleukin-4; interleukin-10; monocytes; periodontitis; Porphyromonas gingivalis ID RHEUMATOID-ARTHRITIS; PERIODONTAL-DISEASE; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; CYSTEINE PROTEINASES; HUMAN MONOCYTES; TH2 CYTOKINES; INTERLEUKIN-10; VIRULENCE; RECEPTORS; MIGRATION AB Background: Chronic periodontitis (CP) is an inflammatory disease in which cytokines play a major role in the progression of disease. Anti-inflammatory cytokines (interleukin 4 [IL-4] and IL-10) were reported to be absent or reduced in diseased periodontal tissues, suggesting an imbalance between the proinflammatory and anti-inflammatory mediators. This study tests the hypothesis that there is cellular crosstalk mediated by proinflammatory and anti-inflammatory cytokines and that blocking proinflammatory cytokine (tumor necrosis factor-alpha [TNF-alpha] and IL-1) production will enhance antiinflammatory cytokine (IL-4 and IL-10) production from peripheral blood mononuclear cells (PBMCs) in response to Porphyromonas gingivalis. Methods: PBMCs were isolated from individuals diagnosed with CP or healthy individuals and cultured for 24 hours. Concanavalin A (ConA) was used as an activator of lymphocyte function. Live and heat-killed P. gingivalis or lipopolysaccharide from P. gingivalis were used as the bacterial stimulants. TNF-alpha and IL-1 production was neutralized by specific antibodies against TNF-alpha and IL-1a or IL-b. Culture supernatants were evaluated by enzyme-linked immunosorbent assay for TNF-alpha, IL-1b, IL-4, and IL-10 production. Results: Live P. gingivalis did not result in any significant IL-10 or IL-4 release, whereas heat-killed P. gingivalis led to a significant increase in IL-10 levels compared with unstimulated or live P. gingivalis-stimulated cells from both healthy individuals or those with CP. Overall, PBMCs from patients with CP produced significantly lower IL-10 in response to ConA and P. gingivalis, suggesting chronic suppression of the anti-inflammatory cytokine production. Blocking the proinflammatory cytokine response did not result in any substantial change in IL-10 or IL-4 response to live P. gingivalis. Blocking the proinflammatory cytokine response restored IL-10 production by cells from CP in response to P. gingivalis lipopolysaccharide. Conclusions: These findings suggest that PBMCs from patients with CP have suppressed anti-inflammatory cytokine production that can, in part, be restored by neutralizing proinflammatory cytokines. Monocytes are an important source of IL-10 production, and monocyte-derived IL-10 might play a regulatory role in the pathogenesis of CP. C1 [Berker, Ezel] Hacettepe Univ, Fac Dent, Dept Periodontol, TR-06100 Ankara, Turkey. [Berker, Ezel; Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org FU National Institutes of Health [DE15566, DE19938]; Scientific and Technical Research Council of Turkey FX This work was supported in part by National Institutes of Health Grants DE15566 and DE19938 (to TVD, HH, and AK) and The Scientific and Technical Research Council of Turkey (to EB). The authors report no conflicts of interest related to this study. NR 44 TC 1 Z9 3 U1 0 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD SEP PY 2013 VL 84 IS 9 BP 1337 EP 1345 DI 10.1902/jop.2012.120422 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 275NZ UT WOS:000328685400018 PM 23173823 ER PT J AU Fradley, MG Barrett, CD Clark, JR Francis, SA AF Fradley, Michael G. Barrett, Conor D. Clark, John R. Francis, Sanjeev A. TI Ventricular Fibrillation Cardiac Arrest due to 5-Fluorouracil Cardiotoxicity SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE Arrhythmias, cardiac/chemically induced; coronary vasospasm/chemically induced; fluorouracil/adverse effects; heart/drug effects; heart diseases/drug therapy; myocarditis/chemically induced; treatment outcome ID MYOCARDITIS; EXPERIENCE; ANGINA; DEFIBRILLATOR; GUIDELINES; DEATH AB The antimetabolite chemotherapeutic agent 5-fluorouracil is used to treat a variety of cancers. Although 5-fluorouracil is generally well tolerated, its toxicity profile includes potential cardiac ischemia, vasospasm, arrhythmia, and direct myocardial injury These actual or potential toxicities are thought to resolve upon cessation of the medication; however, information about the long-term cardiovascular effects of therapy is not sufficient. We present the case of a 58-year-old man who had 2 ventricular fibrillation cardiac arrests, with evidence of coronary vasospasm and myocarditis, on his 4th day of continuous infusion with 5-fluorouracil. External defibrillation and cessation of the 5-fluorouracil therapy resolved the patient's electrocardiographic abnormalities. In addition to reporting the clinical manifestations of 5-fluorouracil associated cardiotoxicity in our patient, we discuss management challenges in patients who develop severe 5-fluorouracil induced ventricular arrhythmias. C1 [Fradley, Michael G.; Barrett, Conor D.; Francis, Sanjeev A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA 02114 USA. [Clark, John R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Hematol & Oncol, Boston, MA 02114 USA. RP Fradley, MG (reprint author), Univ S Florida, Div Cardiovasc Med, 2 Tampa Gen Cir,5th Fl, Tampa, FL 33606 USA. EM mfradley@health.usf.edu NR 21 TC 5 Z9 6 U1 0 U2 2 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 EI 1526-6702 J9 TEX HEART I J JI Tex. Heart Inst. J. PD SEP PY 2013 VL 40 IS 4 BP 472 EP 476 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273FQ UT WOS:000328521000024 PM 24082383 ER PT J AU Elmariah, S Shah, RV Kostis, WJ Hinson, JT Picard, MH Palacios, IF AF Elmariah, Sammy Shah, Ravi V. Kostis, William J. Hinson, J. Travis Picard, Michael H. Palacios, Igor F. TI Coronary Sinus Pacing for the Management of Right Ventricular and Atrial Infarction with Isolated Right Ventricular Pulsus Alternans SO TEXAS HEART INSTITUTE JOURNAL LA English DT Editorial Material C1 [Elmariah, Sammy; Shah, Ravi V.; Kostis, William J.; Hinson, J. Travis; Picard, Michael H.; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, GRB800,55 Fruit St, Boston, MA 02114 USA. EM ipalacios@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 3 TC 0 Z9 0 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 EI 1526-6702 J9 TEX HEART I J JI Tex. Heart Inst. J. PD SEP PY 2013 VL 40 IS 4 BP 497 EP 499 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273FQ UT WOS:000328521000032 PM 24082391 ER PT J AU Issadore, D Chung, HJ Chung, J Budin, G Weissleder, R Lee, H AF Issadore, David Chung, Hyun Jung Chung, Jaehoon Budin, Ghyslain Weissleder, Ralph Lee, Hakho TI mu Hall Chip for Sensitive Detection of Bacteria SO ADVANCED HEALTHCARE MATERIALS LA English DT Article DE Hall; bacterial detection; magnetic nanoparticles ID GRAM-POSITIVE BACTERIA; BIOORTHOGONAL CHEMISTRY; PATHOGEN DETECTION; NANOPARTICLES; INFECTIONS AB Sensitive, rapid and phenotype-specific enumeration of pathogens is essential for the diagnosis of infectious disease, monitoring of food chains, and for defense against bioterrorism. Microbiological culture and genotyping, techniques that sensitively and selectively detect bacteria in laboratory settings, have limited application in clinical environments due to high cost, slow response times, and the need for specially trained staff and laboratory infrastructure. To address these challenges, we developed a microfluidic chip-based micro-Hall (Hall) platform capable of measuring single, magnetically tagged bacteria directly in clinical specimens with minimal sample processing. We demonstrated the clinical utility of the Hall chip by enumerating Gram-positive bacteria. The overall detection limit of the system was similar to that of culture tests (approximate to 10 bacteria), but the assay time was 50-times faster. This low-cost, single-cell analytical technique is especially well-suited to diagnose infectious diseases in resource-limited clinical settings. C1 [Issadore, David; Chung, Hyun Jung; Chung, Jaehoon; Budin, Ghyslain; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu RI Chung, Hyun Jung/J-3205-2014; Issadore, David/L-8451-2014 FU NHLBI [R01-HL113156, HHSN268201000044C, T32CA79443]; NIBIB [R01-EB010011, R01- EB00462605A1] FX We thank N. Sergeyev for the synthesis of cross-linked dextran iron oxide nanoparticles; C. Min, H. Shao and M. Liong for their helpful discussions; Y. Fisher-Jeffes for critically reviewing the manuscript; R.M. Westervelt (Harvard) for generously supporting fabrication of the device. This work was supported in part by NHLBI grants R01-HL113156 (H.L.), NIBIB R01-EB010011 (R.W.), R01- EB00462605A1 (R.W.), NHLBI contract HHSN268201000044C (R.W.), and T32CA79443 (R.W.). NR 24 TC 17 Z9 18 U1 2 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 EI 2192-2659 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD SEP PY 2013 VL 2 IS 9 BP 1224 EP 1228 DI 10.1002/adhm.201200380 PG 5 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA 263PU UT WOS:000327821300007 PM 23495188 ER PT J AU Hughes, J Jouldjian, S Washington, DL Alessi, CA Martin, JL AF Hughes, Jaime Jouldjian, Stella Washington, Donna L. Alessi, Cathy A. Martin, Jennifer L. TI Insomnia and Symptoms of Post-traumatic Stress Disorder Among Women Veterans SO BEHAVIORAL SLEEP MEDICINE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; MAJOR DEPRESSIVE DISORDER; SLEEP QUALITY INDEX; PSYCHIATRIC-DISORDERS; HEALTH-CARE; OF-LIFE; QUESTIONNAIRE; DISTURBANCES; EPIDEMIOLOGY; AFGHANISTAN AB Women will account for 10% of the Veteran population by 2020, yet there has been little focus on sleep issues among women Veterans. In a descriptive study of 107 women Veterans with insomnia (mean age = 49 years, 44% non-Hispanic white), 55% had probable post traumatic stress disorder (PTSD) (total score 33). Probable PTSD was related to more severe self-reported sleep disruption and greater psychological distress. In a regression model, higher PTSD Checklist-Civilian (PCL-C) total score was a significant independent predictor of worse insomnia severity index score while other factors were not. Women Veterans preferred behavioral treatments over pharmacotherapy in general, and efforts to increase the availability of such treatments should be undertaken. Further research is needed to better understand the complex relationship between insomnia and PTSD among women Veterans. C1 [Hughes, Jaime; Jouldjian, Stella] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behav, Los Angeles, CA 90095 USA. [Alessi, Cathy A.; Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90095 USA. RP Martin, JL (reprint author), 16111 Plummer St 11E, North Hills, CA 91343 USA. EM Jennifer.Martin@va.gov FU VA Health Services Research and Development [PPO 09-282-1]; VA Rehabilitation Research and Development [1RX000135-01]; National Institute on Aging [K23 AG028452]; VAGLAHS Geriatric Research, Education, and Clinical Center (GRECC) FX Supported by: VA Health Services Research and Development (PPO 09-282-1), VA Rehabilitation Research and Development (1RX000135-01), National Institute on Aging (K23 AG028452), and the VAGLAHS Geriatric Research, Education, and Clinical Center (GRECC). NR 51 TC 7 Z9 7 U1 5 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1540-2002 EI 1540-2010 J9 BEHAV SLEEP MED JI Behav. Sleep Med. PD SEP 1 PY 2013 VL 11 IS 4 BP 258 EP 274 DI 10.1080/15402002.2012.683903 PG 17 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 268QR UT WOS:000328186100002 PM 23205531 ER PT J AU Barteneva, NS Maltsev, N Vorobjev, IA AF Barteneva, Natasha S. Maltsev, Natalia Vorobjev, Ivan A. TI Microvesicles and intercellular communication in the context of parasitism SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY LA English DT Review DE microvesicles; exosomes; miRNA; parasite; metabolism synchronization; horizontal gene transfer; co-infection; Plasmodium ID OUTER-MEMBRANE VESICLES; CELL-DERIVED MICROVESICLES; EXTRACELLULAR VESICLES; TRYPANOSOMA-CRUZI; CRYPTOCOCCUS-NEOFORMANS; PLASMODIUM-FALCIPARUM; IN-VITRO; VIRULENCE FACTORS; IMMUNE EVASION; FUNCTIONAL-ANALYSIS AB There is a rapidly growing body of evidence that production of microvesicles (MVs) is a universal feature of cellular life. MVs can incorporate microRNA (miRNA), mRNA, mtDNA, DNA and retrotransposons, camouflage viruses/viral components from immune surveillance, and transfer cargo between cells. These properties make MVs an essential player in intercellular communication. Increasing evidence supports the notion that MVs can also act as long-distance vehicles for RNA molecules and participate in metabolic synchronization and reprogramming eukaryotic cells including stem and germinal cells. MV ability to carry on DNA and their general distribution makes them attractive candidates for horizontal gene transfer, particularly between multi-cellular organisms and their parasites; this suggests important implications for the co-evolution of parasites and their hosts. In this review, we provide current understanding of the roles played by MVs in intracellular pathogens and parasitic infections. We also discuss the possible role of MVs in co-infection and host shifting. C1 [Barteneva, Natasha S.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA USA. [Barteneva, Natasha S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. [Maltsev, Natalia] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow, Russia. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, Fac Biol, Dept Cell Biol & Histol, Moscow, Russia. RP Barteneva, NS (reprint author), Program Cellular & Mol Med, 200 Longwood Ave, Boston, MA 02115 USA. EM Natasha.Barteneva@childrens.harvard.edu; maltsev@uchicago.edu FU Harvard Pilot Grant; Program in Cellular and Molecular Medicine; Russian Foundation for Basic Research [11-04-01749a, 13-04-40189H]; Boler Family Foundation FX We are thankful to Dr. Luke Jasenosky for critical reading and Aleksandra Gorelova (Harvard University) for editorial help. Natasha S. Barteneva was supported by Harvard Pilot Grant and Program in Cellular and Molecular Medicine, and Ivan A. Vorobjev was supported by Russian Foundation for Basic Research grants 11-04-01749a and 13-04-40189H. Natalia Maltsev is grateful to Mr. and Ms. Lawrence Hilibrand and the Boler Family Foundation for their generous support of the project. Space considerations limited us to a selected list of available literature. NR 146 TC 36 Z9 39 U1 8 U2 25 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 2235-2988 J9 FRONT CELL INFECT MI JI Front. Cell. Infect. Microbiol. PD SEP PY 2013 VL 3 AR UNSP 49 DI 10.3389/fcimb.2013.00049 PG 11 WC Immunology; Microbiology SC Immunology; Microbiology GA 269TX UT WOS:000328265900002 PM 24032108 ER PT J AU Mateen, FJ Bahl, S Khera, A Sutter, RW AF Mateen, Farrah J. Bahl, Sunil Khera, Ajay Sutter, Roland W. TI Detection of Diphtheritic Polyneuropathy by Acute Flaccid Paralysis Surveillance, India SO EMERGING INFECTIOUS DISEASES LA English DT Article ID GUILLAIN-BARRE-SYNDROME; POLYNEURITIS; RESURGENCE; ADULTS AB Diphtheritic polyneuropathy is a vaccine-preventable illness caused by exotoxin-producing strains of Corynebacterium diphtheriae. We present a retrospective convenience case series of 15 children (6 girls) <15 years of age (mean age 5.2 years, case-fatality rate 53%, and 1 additional case-patient who was ventilator dependent at the time of last follow-up; median follow-up period 60 days) with signs and symptoms suggestive of diphtheritic polyneuropathy. All cases were identified through national acute flaccid paralysis surveillance, which was designed to detect poliomyelitis in India during 2002-2008. We also report data on detection of diphtheritic polyneuropathy compared with other causes of acute flaccid paralysis identified by this surveillance system. C1 [Mateen, Farrah J.] Johns Hopkins Univ, Baltimore, MD USA. [Mateen, Farrah J.; Sutter, Roland W.] World Hlth Org, Geneva, Switzerland. [Bahl, Sunil] World Hlth Org, Natl Polio Surveillance Project, New Delhi, India. [Khera, Ajay] Minist Hlth & Family Welf, New Delhi, India. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,AC 720, Boston, MA 02114 USA. EM fmateen@gmail.com FU American Brain Foundation FX F.J.M. was supported by a research fellowship from the American Brain Foundation. NR 28 TC 3 Z9 3 U1 0 U2 0 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 SEP PY 2013 VL 19 IS 9 BP 1368 EP 1373 DI 10.3201/eid1909.130117 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268MB UT WOS:000328173800002 PM 23965520 ER PT J AU Kelley, JM Daley, GQ AF Kelley, James M. Daley, George Q. TI Hematopoietic defects and iPSC disease modeling: Lessons learned SO IMMUNOLOGY LETTERS LA English DT Review DE Induced pluripotent stem cells; Reprogramming; Disease modeling; Bone marrow failure ID PLURIPOTENT STEM-CELLS; GENETIC CORRECTION; ANEMIA; PATIENT; PROGENITORS; THALASSEMIA; GENERATION; MUTATION AB Hematopoiesis is a paradigm for stem cell biology in that it centers on differentiation of a self-renewing pluripotent precursor into multiple committed cell types with specific functions. The use of induced pluripotent stem cells (iPSCs) as a disease modeling tool has revealed numerous insights into the underlying pathophysiology of hematological diseases - those disorders arising from defective hematopoiesis. Likewise, studying hematopoiesis and the defects that can arise offer clues to understanding general stem cell survival and differentiation. (C) 2013 Elsevier B.V. All rights reserved. C1 [Kelley, James M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kelley, James M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplant Pro, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplant Pro, Boston, MA 02115 USA. EM George.Daley@childrens.harvard.edu FU US National Institute of Diabetes and Digestive and Kidney Diseases [R24-DK092760, RC4-DK090913]; National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium [UO1-HL100001]; National Institutes for Allergy and Immunology [RO1-AI00887]; Alex's Lemonade Stand; Doris Duke Charitable Foundation FX GQD is supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases (R24-DK092760; RC4-DK090913), the National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium (UO1-HL100001) and the National Institutes for Allergy and Immunology (RO1-AI00887; PI Luigi Notarangelo); Alex's Lemonade Stand; and the Doris Duke Charitable Foundation. GQD is an associate member of the Broad Institute, and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. NR 22 TC 2 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 EI 1879-0542 J9 IMMUNOL LETT JI Immunol. Lett. PD SEP-OCT PY 2013 VL 155 IS 1-2 SI SI BP 18 EP 20 DI 10.1016/j.imlet.2013.09.018 PG 3 WC Immunology SC Immunology GA 268NW UT WOS:000328178600006 PM 24076116 ER PT J AU Vecchio, D Dai, TH Huang, LY Fantetti, L Roncucci, G Hamblin, MR AF Vecchio, Daniela Dai, Tianhong Huang, Liyi Fantetti, Lia Roncucci, Gabrio Hamblin, Michael R. TI Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion SO JOURNAL OF BIOPHOTONICS LA English DT Article DE Antimicrobial photodynamic therapy; methicillin resistant Staphylococcus aureus; skin and soft tissue infection; wound healing; cationic zinc phthalocyanine bioluminescence imaging; skin abrasion ID CANDIDA-ALBICANS; ANIMAL-MODELS; INSIGHTS; RATS AB Photodynamic therapy (PDT) is an alternative treatment for infections that can kill drug resistant bacteria without damaging host-tissue. In this study we used bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin abrasion model, to investigate the effect of PDT on bacterial inactivation and wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria in vivo and the possible recurrence in the days post-treatment were monitored by real-time bioluminescence imaging, and wound healing by digital photography. The results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to inhibit bacterial re-growth after the treatment and to significantly accelerate the wound healing process ((c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) C1 [Vecchio, Daniela; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Vecchio, Daniela; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning 530021, Peoples R China. [Fantetti, Lia; Roncucci, Gabrio] Molteni Therapeut, Siena, Italy. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Fondazione MPS by Alta Formazione Internazionale; Airlift Research Foundation Extremity Trauma Research [109421]; US NIH [R01AI050875]; POR CREO FESR FX This work was supported by Fondazione MPS by Alta Formazione Internazionale. Fellowship to D. Vecchio, T. Dai was supported by an Airlift Research Foundation Extremity Trauma Research Grant 109421. M. R. Hamblin was supported by US NIH R01AI050875. L. Fantetti and G. Roncucci were supported by POR CREO FESR 2007-2013 Orione Toscana. The funding agencies had no involvement in planning the study or writing the paper. NR 31 TC 11 Z9 11 U1 2 U2 14 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD SEP PY 2013 VL 6 IS 9 SI SI BP 733 EP 742 DI 10.1002/jbio.201200121 PG 10 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 263NU UT WOS:000327816100008 PM 22987338 ER PT J AU Psaros, C O'Cleirigh, C Bullis, JR Markowitz, SM Safren, SA AF Psaros, Christina O'Cleirigh, Conall Bullis, Jacqueline R. Markowitz, Sarah M. Safren, Steven A. TI The Influence of Psychological Variables on Health-Related Quality of Life among HIV-Positive Individuals with a History of Intravenous Drug Use SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE anxiety; depression; health-related quality of life; HIV; intravenous drug use ID COGNITIVE-BEHAVIORAL THERAPY; SUBSTANCE USE DISORDERS; PSYCHIATRIC-DISORDERS; UNITED-STATES; ANTIRETROVIRAL THERAPY; SERVICES UTILIZATION; ANXIETY DISORDERS; MEDICAL OUTCOMES; DSM-IV; INFECTION AB Objective: Intravenous drug use (IDU) remains a prominent pathway of HIV transmission in the United States, though little is known about modifiable factors influencing quality of life among IDUs. The goal of this study was to evaluate the influence of psychological variables (e. g., depression and anxiety) on health-related quality of life among HIV-positive individuals with a history of IDU who were enrolled in outpatient treatment for opioid dependence. Method: 108 HIV-positive individuals with a history of IDU and participating in current outpatient treatment for opiate dependence who were screened for participation in a depression and adherence study reported sociodemographic data, depressive and anxiety symptoms, and health-related quality of life (HRQoL; Multidimensional Health Assessment using the ACTG-SF 21). Results: Multiple regression models controlling for disease stage and background characteristics identified significant negative relationships between General Health Perception and Functioning without Pain for anxiety and depression, and between Role Functioning and Physical Functioning for anxiety. CD4 cell count was significantly related to Physical Functioning only. Conclusions: Results indicate that distress (both depression and anxiety) contribute significantly to variation in HRQoL over and above the effects of disease variables. Effective depression and anxiety treatment may result in improved overall functioning. C1 [Psaros, Christina; O'Cleirigh, Conall; Bullis, Jacqueline R.; Markowitz, Sarah M.; Safren, Steven A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [Psaros, Christina; Bullis, Jacqueline R.; Markowitz, Sarah M.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Psaros, C (reprint author), Massachusetts Gen Hosp, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM cpsaros@partners.org FU NIDA NIH HHS [R01 DA018603, DA018603]; NIMH NIH HHS [1 K24MH094214, K23 MH096651, K24 MH094214] NR 51 TC 4 Z9 4 U1 5 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0279-1072 EI 2159-9777 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD SEP-OCT PY 2013 VL 45 IS 4 BP 304 EP 312 DI 10.1080/02791072.2013.825030 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 265HS UT WOS:000327941900003 PM 24377169 ER PT J AU Chatterjee, P Agyemang, AF Alimzhanov, MB Degn, S Tsiftsoglou, SA Alicot, E Jones, SA Ma, MH Carroll, MC AF Chatterjee, Priyadarshini Agyemang, Amma F. Alimzhanov, Marat B. Degn, Soren Tsiftsoglou, Stefanos A. Alicot, Elisabeth Jones, Sarah A. Ma, Minghe Carroll, Michael C. TI Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Autoimmunity; Germinal center; Lupus nucleolar antigen; Negative selection ID CLASSICAL PATHWAY COMPLEMENT; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMACYTOID DENDRITIC CELLS; IMMUNE-COMPLEXES; ANTIBODY-RESPONSES; AUTOIMMUNE MICE; SELF-TOLERANCE; DNA; DELETION; GENE AB The factors that allow self-reactive B cells to escape negative selection and become activated remain poorly defined. Using a BCR knock-in mouse strain, we identify a pathway by which B-cell selection to nucleolar self-antigens is complement dependent. Deficiency in complement component C4 led to a breakdown in the elimination of autoreactive B-cell clones at the transitional stage, characterized by a relative increase in their response to a range of stimuli, entrance into follicles, and a greater propensity to form self-reactive GCs. Using mixed BM chimeras, we found that the myeloid compartment was sufficient to restore negative selection in the autoreactive mice. A model is proposed in which in the absence of complement C4, inappropriate clearance of apoptotic debris promotes chronic activation of myeloid cells, allowing the maturation and activation of self-reactive B-cell clones leading to increased spontaneous formation of GCs. C1 [Chatterjee, Priyadarshini; Agyemang, Amma F.; Alimzhanov, Marat B.; Degn, Soren; Tsiftsoglou, Stefanos A.; Alicot, Elisabeth; Jones, Sarah A.; Ma, Minghe; Carroll, Michael C.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Agyemang, Amma F.; Carroll, Michael C.] Harvard Univ, Sch Med, Grad Program Immunol, Div Med Sci, Boston, MA USA. [Agyemang, Amma F.] Harvard Univ, Sch Med, MD PhD Program, Boston, MA USA. RP Carroll, MC (reprint author), Childrens Hosp, Program Cellular & Mol Med, 300 Longwood Ave, Boston, MA 02115 USA. EM Michael.carroll@Childrens.harvard.edu RI Jones, Sarah/I-1458-2013; OI Jones, Sarah/0000-0001-9571-3289; Degn, Soren/0000-0001-5409-045X FU NIH [R01 AI039246, 1 P01 AI078897]; GSK fellowship FX The authors are grateful for the generous gift of 564 Igi mice by Dr. T. Imanishi-Kari (Tufts New England Medical Center). The authors thank Dr. Fritz Melchers for suggestions on the manuscript and Dr. Harry Leung (IDI imaging core) for help with imaging microscopy, and Carlien Frijlink for technical assistance with the manuscript. This work was supported by NIH grants R01 AI039246 (to M.C.C.) and 1 P01 AI078897 (to M.C.C.). P.C. was supported by a GSK fellowship. NR 46 TC 11 Z9 11 U1 1 U2 6 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 SEP PY 2013 VL 43 IS 9 BP 2441 EP 2450 DI 10.1002/eji.201343412 PG 10 WC Immunology SC Immunology GA 263OZ UT WOS:000327819200023 PM 23749435 ER PT J AU Fredericks, WJ McGarvey, T Wang, HY Zheng, YM Fredericks, NJ Yin, HK Wang, LP Hsiao, W Lee, R Weiss, JS Nickerson, ML Kruth, HS Rauscher, FJ Malkowicz, SB AF Fredericks, William J. McGarvey, Terry Wang, Huiyi Zheng, Yongmu Fredericks, Nathaniel J. Yin, Hankun Wang, Li-Ping Hsiao, Wayland Lee, Rob Weiss, Jayne S. Nickerson, Michael L. Kruth, Howard S. Rauscher, Frank J., III Malkowicz, S. Bruce TI The TERE1 Protein Interacts With Mitochondrial TBL2: Regulation of Trans-Membrane Potential, ROS/RNS and SXR Target Genes SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE TERE1; TBL2; MITOCHONDRIA; LIPID METABOLISM; ROS; SXR TARGET GENES ID BREAST-CANCER CELLS; CARCINOMA-CELLS; NITRIC-OXIDE; BLADDER; UBIAD1; CHOLESTEROL; VITAMIN-K-2; ACTIVATION; RECEPTOR; INHIBITION AB We originally discovered TERE1 as a potential tumor suppressor protein based upon reduced expression in bladder and prostate cancer specimens and growth inhibition of tumor cell lines/xenografts upon ectopic expression. Analysis of TERE1 (aka UBIAD1) has shown it is a prenyltransferase enzyme in the natural bio-synthetic pathways for both vitamin K-2 and COQ10 production and exhibits multiple subcellular localizations including mitochondria, endoplasmic reticulum, and golgi. Vitamin K-2 is involved in mitochondrial electron transport, SXR nuclear hormone receptor signaling and redox cycling: together these functions may form the basis for tumor suppressor function. To gain further insight into mechanisms of growth suppression and enzymatic regulation of TERE1 we isolated TERE1 associated proteins and identified the WD40 repeat, mitochondrial protein TBL2. We examined whether disease specific mutations in TERE1 affected interactions with TBL2 and the role of each protein in altering mitochondrial function, ROS/RNS production and SXR target gene regulation. Biochemical binding assays demonstrated a direct, high affinity interaction between TERE1 and TBL2 proteins; TERE1 was localized to both mitochondrial and non-mitochondrial membranes whereas TBL2 was predominantly mitochondrial; multiple independent single amino acid substitutions in TERE1 which cause a human hereditary corneal disease reduced binding to TBL2 strongly suggesting the relevance of this interaction. Ectopic TERE1 expression elevated mitochondrial trans-membrane potential, oxidative stress, NO production, and activated SXR targets. A TERE1-TBL2 complex likely functions in oxidative/nitrosative stress, lipid metabolism, and SXR signaling pathways in its role as a tumor suppressor. J. Cell. Biochem. 114: 2170-2187, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Fredericks, William J.; Wang, Huiyi; Zheng, Yongmu; Fredericks, Nathaniel J.; Yin, Hankun; Malkowicz, S. Bruce] Univ Penn, Dept Surg, Div Urol, Philadelphia, PA 19104 USA. [Fredericks, William J.; Wang, Huiyi; Zheng, Yongmu; Fredericks, Nathaniel J.; Yin, Hankun; Lee, Rob; Malkowicz, S. Bruce] Vet Affairs Med Ctr Philadelphia, Philadelphia, PA 19104 USA. [McGarvey, Terry] Kirksville Osteopath Med Sch, Dept Anat, Kirksville, MO 63501 USA. [Wang, Li-Ping] Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hsiao, Wayland] Weill Cornell Med Coll, Dept Urol, New York, NY USA. [Lee, Rob] Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. [Weiss, Jayne S.] Louisiana State Univ, Dept Ophthalmol, New Orleans, LA USA. [Weiss, Jayne S.] Louisiana State Univ, Ctr Eye, New Orleans, LA 70112 USA. [Nickerson, Michael L.] NCI, Canc & Inflammat Program, Ft Detrick, MD 21702 USA. [Kruth, Howard S.] NIH, Sect Expt Atherosclerosis, Bethesda, MD 20892 USA. [Rauscher, Frank J., III] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Fredericks, WJ (reprint author), VA Med Ctr Philadelphia, Res Bldg 21,Room A418,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM wjfredericks@verizon.net OI Lee, Robert/0000-0001-5826-6686 FU Veterans Affairs Merit Review; Innisfree Foundation of Bryn Mawr, PA; Castleman Family Fund FX Grant sponsor: Veterans Affairs Merit Review; Grant sponsor: The Innisfree Foundation of Bryn Mawr, PA; Grant sponsor: The Castleman Family Fund. NR 50 TC 11 Z9 11 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP PY 2013 VL 114 IS 9 BP 2170 EP 2187 DI 10.1002/jcb.24567 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 261YA UT WOS:000327699500024 PM 23564352 ER PT J AU Grugan, KD Vega, ME Wong, GS Diehl, JA Bass, AJ Wong, KK Nakagawa, H Rustgi, AK AF Grugan, Katharine D. Vega, Maria E. Wong, Gabrielle S. Diehl, J. Alan Bass, Adam J. Wong, Kwok K. Nakagawa, Hiroshi Rustgi, Anil K. TI A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion SO CANCER BIOLOGY & THERAPY LA English DT Article DE p53 mutation; c-Met; esophageal cancer; tumor invasion ID EPIDERMAL-GROWTH-FACTOR; HUMAN ESOPHAGEAL KERATINOCYTES; LI-FRAUMENI-SYNDROME; MUTANT P53; EPITHELIAL-CELLS; CANCER; CARCINOMA; OVEREXPRESSION; MOUSE; CARCINOGENESIS AB Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive forms of human cancer with poor prognosis due to late diagnosis and metastasis. Common genomic alterations in ESCC include p53 mutation, p120ctn inactivation, and overexpression of oncogenes such as cyclin D1, EGFR, and c-Met. Using esophageal epithelial cells transformed by the overexpression of EGFR and p53(R175H), we find novel evidence of a functional link between p53(R175H) and the c-Met receptor tyrosine kinase to mediate tumor cell invasion. Increased c-Met receptor activation was observed upon p53(R175H) expression and enhanced further upon subsequent EGFR overexpression. We inhibited c-Met phosphorylation, resulting in diminished invasion of the genetically transformed primary esophageal epithelial cells (EPC-hTERT-EGFR-p53(R175H)), suggesting that the mechanism of increased invasiveness upon EGFR and p53(R175H) expression may be the result of increased c-Met activation. These results suggest that the use of therapeutics directed at c-Met in ESCC and other squamous cell cancers. C1 [Grugan, Katharine D.; Vega, Maria E.; Wong, Gabrielle S.; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Grugan, Katharine D.; Vega, Maria E.; Wong, Gabrielle S.; Nakagawa, Hiroshi; Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Diehl, J. Alan] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Bass, Adam J.; Wong, Kwok K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rustgi, Anil K.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Rustgi, AK (reprint author), Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. EM anil2@mail.med.upenn.edu FU NIH/NCI [P01 CA098101, U01 CA 143056]; NIH/NIDDK [P30 DK050306]; American Cancer Society [RP-10-033-01-CCE]; NIH [T32 NIH/NRSA F32 DK082149, T32 CA09140, T32 CA115299] FX The authors would like to thank the members of the Rustgi lab for technical support and helpful discussions. This work was supported by NIH/NCI P01 CA098101, NIH/NCI U01 CA 143056, NIH/NIDDK P30 DK050306 Center for Molecular Studies in Digestive and Liver Diseases (and Molecular Pathology and Imaging, Molecular Biology/Gene Expression, Cell Culture Core Facilities), American Cancer Society Grant RP-10-033-01-CCE (AKR) NIH T32 NIH/NRSA F32 DK082149 (KDG), NIH T32 CA09140 (MEV), and NIH T32 CA115299 (GSW). NR 39 TC 4 Z9 5 U1 0 U2 7 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP 1 PY 2013 VL 14 IS 9 BP 853 EP 859 DI 10.4161/cbt.25406 PG 7 WC Oncology SC Oncology GA 256EP UT WOS:000327292800013 PM 23792586 ER PT J AU Zhang, YQ Park, E Kim, CS Paik, JH AF Zhang, Yuqing Park, Eunmi Kim, Christopher S. Paik, Ji-hye TI ZNF365 promotes stalled replication forks recovery to maintain genome stability SO CELL CYCLE LA English DT Article ID STRAND BREAK REPAIR; HOMOLOGY-DIRECTED REPAIR; COMMON FRAGILE SITES; DNA-DAMAGE RESPONSE; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS; END RESECTION; S-PHASE; RECOMBINATION; CANCER C1 [Zhang, Yuqing; Kim, Christopher S.; Paik, Ji-hye] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Park, Eunmi] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Paik, JH (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. EM jep2025@med.cornell.edu FU Ellison Medical Foundation [AG-NS-0646-10]; Sidney Kimmel Foundation [SKF-092] FX J-HP is supported by the Ellison Medical Foundation (AG-NS-0646-10) and the Sidney Kimmel Foundation (SKF-092). NR 46 TC 4 Z9 5 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD SEP 1 PY 2013 VL 12 IS 17 BP 2817 EP 2828 PG 12 WC Cell Biology SC Cell Biology GA 258CJ UT WOS:000327436300020 PM 23966166 ER PT J AU Ruchat, SM Houde, AA Voisin, G St-Pierre, J Perron, P Baillargeon, JP Gaudet, D Hivert, MF Brisson, D Bouchard, L AF Ruchat, Stephanie-May Houde, Andree-Anne Voisin, Gregory St-Pierre, Julie Perron, Patrice Baillargeon, Jean-Patrice Gaudet, Daniel Hivert, Marie-France Brisson, Diane Bouchard, Luigi TI Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases SO EPIGENETICS LA English DT Article DE epigenetics; epigenome-wide; in utero; maternal hyperglycemia; DNA methylation; fetal metabolic programming ID DNA METHYLATION; INTRAUTERINE EXPOSURE; WEIGHT-GAIN; ASSOCIATION; OBESITY; PREGNANCY; CHILDREN; BIRTH; EXPRESSION; ADIPOSITY AB Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring's methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24-28 weeks of pregnancy. DNA methylation was measured at > 485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 x 10(-06); none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 +/- 3.2% and 3.4 +/- 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 x 10(-13) < p < 4.0 x 10(-03); including diabetes mellitus p = 4.3 x 10(-11)). Among the differentially methylated genes, 326 in placenta and 117 in cord blood were also associated with newborn weight. Our results therefore suggest that GDM has epigenetic effects on genes preferentially involved in the metabolic diseases pathway, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming. C1 [Ruchat, Stephanie-May; Houde, Andree-Anne; Bouchard, Luigi] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Ruchat, Stephanie-May; Houde, Andree-Anne; St-Pierre, Julie; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, ECOGENE Lab & Lipid Clin 21, Saguenay, PQ, Canada. [Voisin, Gregory] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [St-Pierre, Julie] Chicoutimi Hosp, Dept Pediat, Saguenay, PQ, Canada. [Perron, Patrice; Baillargeon, Jean-Patrice; Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Gaudet, Daniel; Brisson, Diane] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Bouchard, L (reprint author), Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. EM luigi.bouchard@usherbrooke.ca FU ECOGENE-21; Canadian Institutes of Health Research (CIHR) [CTP-82941]; CIHR; Fonds de la Recherche du Quebec, Sante (FRQ-S); Canadian Diabetes Association; Diabete Quebec; Faculty of Medicine and Health Sciences; Universite de Sherbrooke; FRQ-S; Canadian Diabetes Association clinical scientist award FX This project was supported by ECOGENE-21, the Canadian Institutes of Health Research (CIHR team in community genetics [grant #CTP-82941]), the CIHR and Fonds de la Recherche du Quebec, Sante (FRQ-S). SMR is recipient of a postdoctoral fellowship from the Canadian Diabetes Association. AAH is a recipient of a scholarship from Diabete Quebec, the Faculty of Medicine and Health Sciences, Universite de Sherbrooke and the FRQ-S. LB and MFH are junior research scholars from the FRQ-S. MFH is also supported by a Canadian Diabetes Association clinical scientist award. LB, MFH, PP and JPB are members of the FRQ-S-funded Centre de recherche clinique Etienne-Le Bel (affiliated to Centre Hospitalier de l'Universite de Sherbrooke). NR 43 TC 60 Z9 61 U1 2 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PD SEP 1 PY 2013 VL 8 IS 9 BP 935 EP 943 DI 10.4161/epi.25578 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 260WG UT WOS:000327624600007 PM 23975224 ER PT J AU Xue, Y Xing, Z Bolstad, AI Van Dyke, TE Mustafa, K AF Xue, Ying Xing, Zhe Bolstad, Anne Isine Van Dyke, Thomas E. Mustafa, Kamal TI Co-culture of human bone marrow stromal cells with endothelial cells alters gene expression profiles SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article DE MSC EC coculture; Microarray ID MESENCHYMAL STEM-CELLS; IN-VITRO; TGF-BETA; DIFFERENTIATION; GROWTH; REGENERATION AB The intricate relationship between angiogenesis and osteogenesis in vivo must be replicated in bone tissue engineering constructs to ensure the formation of a functional vascular network to support successful bone formation. Although communication between bone marrow stromal cells (MSC) and endothelial cells (EC) is recognized as one of the most important cellular interactions in bone regeneration, the underlying mechanisms of this biological process are not well understood. The purpose of this study was to analyze global gene expression associated with intercellular communication between MSC and EC using HumanWG-6 v3.0 expression BeadChips with a one-channel platform system (Illumina, San Diego, CA, USA). Each array contains more than 48,000 probes derived from human genes. A global map of MSC gene expression was generated following co-culture of MSC with EC for 5 and 15 days, in a direct-contact model. The map was used to determine relative alterations in functional processes and pathways. Co-culturing EC with MSC up-regulated genes related to angiogenesis as von Willebrand factor, platelet/endothelial cell adhesion molecule-1, cadherin 5, angiopoietin-related protein 4, and cell surface antigen CD34, and genes playing important roles in osteogenesis as alkaline phosphatase, FK506 binding protein 5, and bone morphogenetic protein. These findings clearly demonstrated that EC had a significant impact on MSC, particularly the bidirectional regulation of angiogenesis and osteogenesis. Moreover, cell-matrix interactions and TGF-beta signal pathways were implicated for a crucial role in endothelial, cell-induced gene regulation in MSCs. A detailed study of the functional correlates of the microarray data is warranted to explore cellular and molecular interactions of importance in bone tissue engineering. C1 [Xue, Ying; Xing, Zhe; Mustafa, Kamal] Univ Bergen, Dept Clin Dent, Ctr Clin Dent Res, N-5020 Bergen, Norway. [Bolstad, Anne Isine] Univ Bergen, Dept Clin Dent Periodont, N-5020 Bergen, Norway. [Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. RP Xue, Y (reprint author), Univ Bergen, Fac Med & Dent, Ctr Clin Dent Res, Dept Clin Dent, Arstadveien 19 POB 7800, N-5020 Bergen, Norway. EM Ying.xue@uib.no RI Xing, Zhe/D-9743-2014 FU VascuBone project; European Union [242175]; Research Council of Norway [Stem Cell 180383/V40, 17734/V50, 156744]; USPHS from the National Institute of Dental and Craniofacial Research [R01-DE19938] FX This project was supported by the VascuBone project, European Union FP7; grant number: 242175; The Research Council of Norway ((Stem Cell 180383/V40), (FRIMED, 17734/V50), (156744)); and supported in part by USPHS grant R01-DE19938 from the National Institute of Dental and Craniofacial Research. NR 20 TC 4 Z9 4 U1 1 U2 15 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 EI 1724-6040 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD SEP PY 2013 VL 36 IS 9 BP 650 EP 662 DI 10.5301/ijao.5000229 PG 13 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 257WR UT WOS:000327419000007 PM 23918270 ER PT J AU Haq, R Fisher, DE AF Haq, Rizwan Fisher, David E. TI Improving apoptotic responses to targeted therapy SO ONCOTARGET LA English DT Editorial Material ID INHIBITOR; RESISTANCE; MELANOMA; CANCER; CELLS C1 [Haq, Rizwan; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Haq, R (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM rhaq@partners.org; dfisher3@partners.org FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369] NR 9 TC 1 Z9 1 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD SEP PY 2013 VL 4 IS 9 BP 1331 EP 1331 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 257QJ UT WOS:000327400300002 PM 23934756 ER PT J AU Li, DP Ilnytskyy, Y Kovalchuk, A Khachigian, LM Bronson, RT Wang, B Kovalchuk, O AF Li, Dongping Ilnytskyy, Yaroslav Kovalchuk, Anna Khachigian, Levon M. Bronson, Roderick T. Wang, Bo Kovalchuk, Olga TI Crucial Role for Early Growth Response-1 in the Transcriptional Regulation of miR-20b in Breast Cancer SO ONCOTARGET LA English DT Article DE EGR1; miR-20b; transcription; PTEN; BRCA1; breast cancer; proliferation; migration; cell cycle arrest ID INHIBITS TUMOR ANGIOGENESIS; MUSCLE-CELL PROLIFERATION; HUMAN PROSTATE-CANCER; GENE-EXPRESSION; FACTOR EGR-1; POSTTRANSCRIPTIONAL REGULATION; MICRORNA CLUSTER; LUNG CANCERS; FACTOR-I; C-MYC AB Transcriptional regulation of miRNAs that control the pathogenesis of breast cancer remains largely unknown. Here, we showed that ionizing radiation, a known breast carcinogen, triggered the differential expression of miR-20b in mammary tissues. We identified several GC-rich consensus binding motifs for the zinc finger transcription factor early growth response-1 (EGR1) in miR-20b promoter. miR-20b was upregulated by IR and its upregulation correlated with EGR1 expression in the breast cancer cell line HCC1806. Therefore, we used HCC1806 cells as a model system to explore the role of EGR1 in miR-20b transcription. siRNA knockdown of EGR1 attenuated miR-20b expression. Luciferase assays showed that whereas EGR1 stimulated luciferase activity driven by the wild-type miR-20b promoter, this induction was abolished in the mutant miR-20b promoter construct. We noted significant enrichment of EGR1 at miR-20b promoter in HCC1806 cells compared with normal human mammary epithelial cells. Suppression of miR-20b significantly inhibited HCC1806 cell proliferation and migration, and led to G(0)/G(1) and S phase arrest. In vitro RNA-pull down assays indicated that miR-20b targets numerous tumor suppressors, including PTEN and BRCA1, which were downregulated in HCC1806. Conversely, suppression of miR-20b increased PTEN and BRCA1 levels. Moreover, immunohistochemical and FISH analyses showed that the miR-20b expression correlated significantly with EGR1 levels in breast cancer tissues. Our findings thus demonstrate for the first time that EGR1 is a key player in the transcriptional control of miR-20b, and miR-20b may in turn function as an oncogene by contributing to breast tumorigenesis via tumor suppressor targeting. C1 [Li, Dongping; Ilnytskyy, Yaroslav; Kovalchuk, Anna; Wang, Bo; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Li, Dongping; Wang, Bo] Qiqihar Med Univ, Dept Biochem, Qiqihar, Peoples R China. [Khachigian, Levon M.] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. [Bronson, Roderick T.] Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca FU Alberta Cancer Foundation/Alberta Innovates-Health Solutions; Canadian Breast Cancer Foundation; Alberta Innovates-Health Solutions Postdoctoral Fellowship FX This study was supported by Alberta Cancer Foundation/Alberta Innovates-Health Solutions and the Canadian Breast Cancer Foundation grants to Dr. O. Kovalchuk. Dr. B. Wang is a recipient of the Alberta Innovates-Health Solutions Postdoctoral Fellowship. We thank Ms. Lida Luzhna for providing IR-exposed rat mammary gland tissue, and Mr. Julian St. Hilaire for performing the BD FACSCanto II Flow Cytometer. NR 62 TC 20 Z9 21 U1 2 U2 6 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD SEP PY 2013 VL 4 IS 9 BP 1373 EP 1387 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 257QJ UT WOS:000327400300009 PM 23945289 ER PT J AU Manchikanti, L Benyamin, RM Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin M. Falco, Frank J. E. Hirsch, Joshua A. TI Recommendations of the Medicare Payment Advisory Commission (MEDPAC) on the Health Care Delivery System: The Impact on Interventional Pain Management in 2014 and Beyond SO PAIN PHYSICIAN LA English DT Review DE Medicare; health care delivery system; Medicare Payment Advisory Commission (MedPAC); hospital outpatient departments (HOPDs); ambulatory surgery centers (ASCs); physician office practices ID LOW-BACK-PAIN; FACET JOINT INTERVENTIONS; EPIDURAL STEROID INJECTIONS; LUMBAR SURGERY SYNDROME; COST-EFFECTIVENESS; SPINAL-STENOSIS; UNITED-STATES; EXERCISE THERAPY; DISC-HERNIATION; DEGENERATIVE-SPONDYLOLISTHESIS AB Continuing rise in health care costs in the United States, the Affordable Care Act (ACA), and a multitude of other regulations impact providers in 2013. Despite federal spending slowing in the past 2 years, the Board of Medicare Trustees believes that cost savings are only achievable if health care providers are able to realize productivity improvements at a quicker pace than experienced historically. Consequently, the re-engineering of U. S. health care and bridging of the divide between health and health care have been proposed beyond affordable care. Thus, the Medicare Payment Advisory Commission (MedPAC) envisions alignment of Medicare payment systems to eliminate variable rates for the same ambulatory services provided to similar patients in different settings, such as the physician's office, hospital outpatient departments (HOPDs), and ambulatory surgery centers (ASCs). MedPAC believes that if the same service can be safely provided in different settings, a prudent purchaser should not pay more for that service in one setting than in another. MedPAC is also concerned that payment variations across settings encourage arrangements among providers that result in care being provided in high paid settings. MedPAC recommends that payment rates be based on the resources needed to treat patients in the most efficient setting, adjusting for differences in patient severity, to the extent the severity differences affect costs. MedPAC has analyzed the costs of evaluation and management (E&M) services and the differences between providing them in a HOPD setting compared to a physician office setting, echocardiography services, and multiple services provided in ASCs and HOPDs. MedPAC has shown that for an established patient office visit (CPT 99213) provided in a free-standing physician's office, the program pays the physician 70% less than in HOPD setting with a payment for physician practice of $72.50 versus $123.38 for HOPD setting. Similarly, for a Level II echocardiogram, HOPD costs 141% more for the same service than a free-standing office ($188.31 versus $452.89). For interventional techniques, Medicare payments vary from physician office to HOPD setting, with $211.96 in an office setting, $407.28 in ASC setting, and $655.62 in HOPD for procedures such as epidural injections. The MedPAC proposal for changing HOPD payment rates for services would reduce program spending and result in beneficiary cost sharing by $900 million in one year. On average, hospitals' overall Medicare revenue will decline by 0.6% and HOPD revenue would fall by 2.7%. Further, MedPAC provided a specific example that aligning payment rates between HOPDs and freestanding offices only for cardiac imaging services would reduce program spending and beneficiary cost sharing by $500 million in one year. In estimating the savings that would be realized by equalizing payment rates between HOPDs and ASCs for certain ambulatory surgical procedures, MedPAC have shown potential Medicare program spending and beneficiary cost savings to be about $590 million per year. The impact of the proposed policies that are discussed in this manuscript would result in savings of approximately $1.5 billion per year for Medicare. MedPAC also has recommended a stop-loss policy that would limit the loss of Medicare revenue for those hospitals. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Pain Med Fellowship Program, Philadelphia, PA 19140 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Endovasc Neurosurg & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 110 TC 8 Z9 8 U1 9 U2 11 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 SEP-OCT PY 2013 VL 16 IS 5 BP 419 EP 440 PG 22 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 259SU UT WOS:000327547400019 PM 24077189 ER PT J AU Verrier, RL Ikeda, T AF Verrier, Richard L. Ikeda, Takanori TI Ambulatory ECG-Based T-Wave Alternans Monitoring for Risk Assessment and Guiding Medical Therapy: Mechanisms and Clinical Applications SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE T-wave alternans; Heterogeneity of repolarization; Risk stratification; Arrhythmia; Sudden cardiac death; Cardiovascular mortality ID SUDDEN CARDIAC DEATH; HEART-RATE TURBULENCE; LEFT-VENTRICULAR DYSFUNCTION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; ACUTE MYOCARDIAL-ISCHEMIA; ACUTE-CORONARY-SYNDROME; SODIUM-CHANNEL BLOCKER; ST-SEGMENT-ELEVATION; ELECTRICAL INSTABILITY; BRUGADA-SYNDROME AB Identification of individuals at risk for sudden cardiac death (SCD), the main cause of adult mortality in developed countries, remains a major challenge. The main contemporary noninvasive marker, left ventricular ejection fraction (LVEF), has not proved adequately reliable, as the majority of individuals who die suddenly have relatively preserved cardiac mechanical function. Monitoring of T-wave alternans (TWA), a beat-to-beat fluctuation in ST-segment or T-wave morphology, on ambulatory electrocardiogram (AECG) is an attractive approach on both scientific and clinical grounds. Specifically, TWA's capacity to assess risk for malignant arrhythmias has been shown to rest on sound electrophysiologic principles and AECG-based TWA monitoring can be performed in the flow of routine clinical evaluation. This review addresses: (1) electrophysiologic and ionic mechanisms underlying TWA's predictivity, (2) principles and practical aspects of AECG-based TWA monitoring, (3) clinical evidence supporting this approach to SCD risk stratification, and (4) current and potential applications in guiding medical therapy. (C) 2013 Elsevier Inc. All rights reserved. C1 [Verrier, Richard L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ikeda, Takanori] Toho Univ, Med Ctr, Fac Med, Tokyo, Japan. RP Verrier, RL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 99 Brookline Ave,RN 301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu FU Gilead Sciences, Inc. FX Dr. Verrier is co-inventor of the Modified Moving Average method for T-wave alternans analysis, with patent assigned to Georgetown University and Beth Israel Deaconess Medical Center and licensed to GE Healthcare, Inc., and Medtronic, Inc. He receives research grants from Gilead Sciences, Inc. NR 82 TC 18 Z9 19 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 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2013 VL 56 IS 2 BP 172 EP 185 DI 10.1016/j.pcad.2013.07.002 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 257VK UT WOS:000327415700007 PM 24215749 ER PT J AU Kilbourne, AM Deeghan, T Jones, KR AF Kilbourne, Amy M. Deeghan, Tisha Jones, Kenneth R. TI Serious Mental Illness and Weight Management Interventions SO PSYCHIATRIC SERVICES LA English DT Letter C1 [Kilbourne, Amy M.] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Ctr Clin Management Res, Ann Arbor, MI USA. [Deeghan, Tisha] Genesee Hlth Syst, Flint, MI USA. [Jones, Kenneth R.] VHA Natl Ctr Hlth Promot & Dis Prevent, Durham, NC USA. RP Kilbourne, AM (reprint author), US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Ctr Clin Management Res, Ann Arbor, MI USA. NR 5 TC 0 Z9 0 U1 6 U2 7 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 SEP PY 2013 VL 64 IS 9 BP 931 EP 931 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255ZC UT WOS:000327277600021 PM 24026842 ER PT J AU Okwemba, R Medvedeva, E Wang, A AF Okwemba, Robert Medvedeva, Elina Wang, Andrew TI Medication Adherence Among Patients With Comorbid Diabetes SO PSYCHIATRIC SERVICES LA English DT Letter ID SCHIZOPHRENIA C1 [Okwemba, Robert; Medvedeva, Elina; Wang, Andrew] Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. RP Okwemba, R (reprint author), Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. NR 3 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 2013 VL 64 IS 9 BP 934 EP 935 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255ZC UT WOS:000327277600025 PM 24026846 ER PT J AU Stoeckel, LE Stewart, CC Griffith, HR Triebel, K Okonkwo, OC den Hollander, JA Martin, RC Belue, K Copeland, JN Harrell, LE Brockington, JC Clark, DG Marson, DC AF Stoeckel, Luke E. Stewart, Christopher C. Griffith, H. Randall Triebel, Kristen Okonkwo, Ozioma C. den Hollander, Jan A. Martin, Roy C. Belue, Katherine Copeland, Jacquelynn N. Harrell, Lindy E. Brockington, John C. Clark, David G. Marson, Daniel C. TI MRI volume of the medial frontal cortex predicts financial capacity in patients with mild Alzheimer's disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Alzheimer's disease; Financial capacity; Magnetic resonance imaging; Frontal cortex; Precuneus; Angular gyrus ID DEMENTIA RATING-SCALE; MINI-MENTAL-STATE; COGNITIVE IMPAIRMENT; PREFRONTAL CORTEX; HIPPOCAMPAL ATROPHY; ABILITIES; ATTENTION; BRAIN; LIFE; CAREGIVERS AB Persons with mild Alzheimer's disease (AD) have significant deficits in financial abilities. This study examined the relationship between brain structure volumes, cognition, and financial capacity in patients with mild AD. Sixteen mild AD patients and 16 older adult comparisons completed the Financial Capacity Instrument (FCI), a psychometric measure of financial abilities, and also underwent magnetic resonance imaging (MRI) to obtain volumes of the bilateral hippocampi, angular gyri, precunei, and medial and dorsolateral frontal cortices. Mild AD patients performed significantly below comparisons on the FCI and had significantly smaller hippocampi. Among mild AD patients, FCI performance was moderately correlated with frontal (medial and dorsolateral frontal cortex) and posterior (angular gyri and precunei) cortical volumes. Stepwise regression demonstrated that medial frontal cortex volume predicted FCI score. The relationship between medial frontal cortex volume and overall FCI score was partially mediated by two measures of simple attention (DRS Attention, DRS Construction). The findings suggest that medial frontal cortex atrophy and associated declines in simple attention play an increasingly important role in declining financial skills in patients with mild AD. C1 [Stoeckel, Luke E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stoeckel, Luke E.] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, Christopher C.] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA. [Griffith, H. Randall; Triebel, Kristen; Martin, Roy C.; Belue, Katherine; Harrell, Lindy E.; Brockington, John C.; Clark, David G.; Marson, Daniel C.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Griffith, H. Randall; Triebel, Kristen; Martin, Roy C.; Belue, Katherine; Harrell, Lindy E.; Brockington, John C.; Clark, David G.; Marson, Daniel C.] Univ Alabama Birmingham, Dept Alzheimers Dis Res Ctr, Birmingham, AL 35294 USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Alzheimers Dis Res Ctr, Madison, WI USA. [den Hollander, Jan A.] Univ Alabama Birmingham, Dept Cardiol, Birmingham, AL USA. [Copeland, Jacquelynn N.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. [Harrell, Lindy E.; Clark, David G.] Birmingham Reg Vet Affairs Med Ctr, Birmingham, AL USA. RP Stoeckel, LE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM lstoeckel@partners.org; christopher_stewart@rush.edu; dmarson@uab.edu FU National Institute on Aging (Alzheimer's Disease Research Center) [1P50 AG16582-10, 1R01 AG021927-05, 5R01 AG021927]; Alzheimer's of Central Alabama, the National Institute of Drug Abuse [K23 DA032612]; Brain & Behavior Research Foundation Young Investigator Award; Charles A. King Trust FX This study was funded by grants from the National Institute on Aging (Alzheimer's Disease Research Center-1P50 AG16582-10: Marson, PI); (1R01 AG021927-05: Marson, PI); (5R01 AG021927: Marson, PI), Alzheimer's of Central Alabama, the National Institute of Drug Abuse (K23 DA032612: Stoeckel, PI), the Brain & Behavior Research Foundation Young Investigator Award (Stoeckel, PI), and the Charles A. King Trust Fellowship (Stoeckel, PI). The authors would like to thank Julia Stern and Caroline Chan for their assistance with manuscript preparation. NR 53 TC 4 Z9 4 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2013 VL 7 IS 3 BP 282 EP 292 DI 10.1007/s11682-013-9226-3 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA 253GG UT WOS:000327071400006 PM 23504597 ER PT J AU Kikinis, Z Makris, N Finn, CT Bouix, S Lucia, D Coleman, MJ Tworog-Dube, E Kikinis, R Kucherlapati, R Shenton, ME Kubicki, M AF Kikinis, Zora Makris, Nikos Finn, Christine T. Bouix, Sylvain Lucia, Diandra Coleman, Michael J. Tworog-Dube, Erica Kikinis, Ron Kucherlapati, Raju Shenton, Martha E. Kubicki, Marek TI Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE 22q11.2 deletion syndrome (22q11.2DS, VCFS); Diffusion Tensor MRI (DT-MRI); Fractional anisotropy (FA); Axial diffusivity (AD); Inferior fronto-occipital fasciculus (IFOF); Inferior longitudinal fasciculus (ILF); High-risk schizophrenia ID CARDIO-FACIAL SYNDROME; INFERIOR LONGITUDINAL FASCICULUS; WHITE-MATTER MICROSTRUCTURE; VELOCARDIOFACIAL SYNDROME; RADIAL DIFFUSIVITY; SCHIZOPHRENIA; CHILDREN; ADOLESCENTS; BRAIN; MRI AB Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA, measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS. C1 [Kikinis, Zora; Makris, Nikos; Bouix, Sylvain; Lucia, Diandra; Coleman, Michael J.; Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Makris, Nikos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Makris, Nikos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Finn, Christine T.] Dartmouth Hitchcock Med Ctr, Dept Psychiat, Lebanon, NH 03766 USA. [Tworog-Dube, Erica] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Kikinis, Ron; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Surg Planning Lab, Boston, MA 02115 USA. [Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Dept Psychiat, Clin Neurosci Div,Lab Neurosci,VA Boston Healthca, Brockton, MA USA. RP Kikinis, Z (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02115 USA. EM zora@bwh.harvard.edu OI Bouix, Sylvain/0000-0003-1326-6054 FU Brain and Behavior Research Foundation; US Department of Veterans Affairs; US Department of Veterans Affairs (Schizophrenia Center); National Institute of Health [MH 50740, MH 070047, MH 080272, RO1 MH082918, U54 EB005149, NAC P41 RR 13218] FX This work was supported by a Brain and Behavior Research Foundation (formerly called NARSAD) (Young Investigator Award to ZK); by the US Department of Veterans Affairs (Merit Awards to MES), (Schizophrenia Center to MES); and by National Institute of Health (Career Reentry Supplement to ZK on MH 50740 to MES), (MH 070047 to MES), (MH 080272 to MES and to MK), (RO1 MH082918 to SB)(U54 EB005149 to RK, to MK, to MES); (NAC P41 RR 13218 to RK). NR 66 TC 8 Z9 8 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2013 VL 7 IS 3 BP 316 EP 325 DI 10.1007/s11682-013-9232-5 PG 10 WC Neuroimaging SC Neurosciences & Neurology GA 253GG UT WOS:000327071400010 PM 23612843 ER PT J AU Makris, N Preti, MG Wassermann, D Rathi, Y Papadimitriou, GM Yergatian, C Dickerson, BC Shenton, ME Kubicki, M AF Makris, N. Preti, M. G. Wassermann, D. Rathi, Y. Papadimitriou, G. M. Yergatian, C. Dickerson, B. C. Shenton, M. E. Kubicki, M. TI Human middle longitudinal fascicle: segregation and behavioral-clinical implications of two distinct fiber connections linking temporal pole and superior temporal gyrus with the angular gyrus or superior parietal lobule using multi-tensor tractography SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE High-angular resolution diffusion imaging; Middle longitudinal fascicle; Middle longitudinal fasciculus; Angulargyrus; Superior parietal lobule; Primary progressive aphasia; Neurodegenerative disorders ID HUMAN CEREBRAL-CORTEX; PRIMARY PROGRESSIVE APHASIA; RIGHT-HEMISPHERE DOMINANCE; SURFACE-BASED ANALYSIS; RHESUS-MONKEY; WHITE-MATTER; HUMAN BRAIN; IN-VIVO; DT-MRI; ALZHEIMERS-DISEASE AB The middle longitudinal fascicle (MdLF) is a major fiber connection running principally between the superior temporal gyrus and the parietal lobe, neocortical regions of great biological and clinical interest. Although one of the most prominent cerebral association fiber tracts, it has only recently been discovered in humans. In this high angular resolution diffusion imaging (HARDI) MRI study, we delineated the two major fiber connections of the human MdLF, by examining morphology, topography, cortical connections, biophysical measures, volume and length in seventy-four brains. These two fiber connections course together through the dorsal temporal pole and the superior temporal gyrus maintaining a characteristic topographic relationship in the mediolateral and ventrodorsal dimensions. As these pathways course towards the parietal lobe, they split to form separate fiber pathways, one following a ventrolateral trajectory and connecting with the angular gyrus and the other following a dorsomedial route and connecting with the superior parietal lobule. Based on the functions of their cortical affiliations, we suggest that the superior temporal-angular connection of the MdLF, i.e., STG(MdLF)AG plays a role in language and attention, whereas the superior temporal-superior parietal connection of the MdLF, i.e., STG(MdLF)SPL is involved in visuospatial and integrative audiovisual functions. Furthermore, the MdLF may have clinical implications in neurodegenerative disorders such as primary progressive aphasia, frontotemporal dementia, posterior cortical atrophy, corticobulbar degeneration and Alzheimer's disease as well as attention-deficit/hyperactivity disorder and schizophrenia. C1 [Makris, N.; Papadimitriou, G. M.; Yergatian, C.; Dickerson, B. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat Serv,Ctr Neural Syst Invest,Ctr Mor, Charlestown, MA 02129 USA. [Makris, N.; Papadimitriou, G. M.; Yergatian, C.; Dickerson, B. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol Serv,Ctr Neural Syst Invest,Ctr Morph, Charlestown, MA 02129 USA. [Makris, N.; Wassermann, D.; Rathi, Y.; Yergatian, C.; Shenton, M. E.; Kubicki, M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiatry, Boston, MA 02115 USA. [Makris, N.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02115 USA. RP Makris, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat Serv,Ctr Neural Syst Invest,Ctr Mor, Bldg 149,13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu FU NIDA [1R01DA027804-01]; NINDS [R21NS077059]; National Institute of Health [K05 MH070047, R01 MH 50740, P50MH 080272, R01 M074794]; Department of Veterans Affairs Merit Award; VA Schizophrenia Center Grant; National Alliance for Medical Image Computing (NA-MIC); National Institutes of Health Roadmap for Medical Research [U54 EB005149]; Progetto Roberto Rocca Foundation FX This study was supported, in part, by grants from: NIDA 1R01DA027804-01 (NM), NINDS R21NS077059 (NM and BCD); the National Institute of Health (K05 MH070047 and R01 MH 50740 (MES), P50MH 080272-CIDAR award (MES and MK), R01 M074794 (MK), the Department of Veterans Affairs Merit Award (MES), the VA Schizophrenia Center Grant (MES); the National Alliance for Medical Image Computing (NA-MIC), the latter a grant supported through the National Institutes of Health Roadmap for Medical Research, Grant U54 EB005149 (MK, MES); Progetto Roberto Rocca Foundation (MGP). The authors would like to thank Dr. Lichen Liang for his contribution to this manuscript. NR 83 TC 13 Z9 13 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2013 VL 7 IS 3 BP 335 EP 352 DI 10.1007/s11682-013-9235-2 PG 18 WC Neuroimaging SC Neurosciences & Neurology GA 253GG UT WOS:000327071400012 PM 23686576 ER PT J AU Doherty, K Ciaranello, A AF Doherty, Katie Ciaranello, Andrea TI What is needed to eliminate new pediatric HIV infections: the contribution of model-based analyses SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE cost-effectiveness; elimination; modeling; pediatric HIV; prevention of mother-to-child HIV transmission ID TO-CHILD-TRANSMISSION; COST-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; PRETERM DELIVERY; PREVENTION; PREGNANCY; INFANTS; HEALTH; NEVIRAPINE; RECOMMENDATIONS AB Purpose of reviewComputer simulation models can identify key clinical, operational, and economic interventions that will be needed to achieve the elimination of new pediatric HIV infections. In this review, we summarize recent findings from model-based analyses of strategies for prevention of mother-to-child HIV transmission (MTCT).Recent findingsIn order to achieve elimination of MTCT (eMTCT), model-based studies suggest that scale-up of services will be needed in several domains: uptake of services and retention in care (the PMTCT cascade'), interventions to prevent HIV infections in women and reduce unintended pregnancies (the four-pronged approach'), efforts to support medication adherence through long periods of pregnancy and breastfeeding, and strategies to make breastfeeding safer and/or shorter. Models also project the economic resources that will be needed to achieve these goals in the most efficient ways to allocate limited resources for eMTCT. Results suggest that currently recommended PMTCT regimens (WHO Option A, Option B, and Option B+) will be cost-effective in most settings.SummaryModel-based results can guide future implementation science, by highlighting areas in which additional data are needed to make informed decisions and by outlining critical interventions that will be necessary in order to eliminate new pediatric HIV infections. C1 [Doherty, Katie] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Gen Med, Boston, MA 02114 USA. [Ciaranello, Andrea] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Doherty, K (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM kdoherty6@partners.org FU National Institutes of Health, National Institute of Allergy and Infectious Disease [K01 AI078754, R01 AI058736]; International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT); March of Dimes Foundation; Massachusetts General Hospital Executive Committee on Research; National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG) [5 U01 AI41110]; IMPAACT Group [1 U01 AI068616]; National Institute of Allergy and Infectious Diseases (NIAID); NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD [N01-DK-9-001/HHSN267200800001C] FX Support for this work was provided by the National Institutes of Health, including the National Institute of Allergy and Infectious Disease (K01 AI078754 (A. C.); R01 AI058736 (K. D.); and the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT: K. D., A. C.), as well as the March of Dimes Foundation (K. D.) and the Massachusetts General Hospital Executive Committee on Research (A. C.). Overall support for IMPAACT was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). NR 58 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD SEP PY 2013 VL 8 IS 5 BP 457 EP 466 DI 10.1097/COH.0b013e328362db0d PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 248US UT WOS:000326730500013 PM 23743788 ER PT J AU Bulka, CM Cassedy, EA Sandberg, WS Ehrenfeld, JM AF Bulka, Catherine M. Cassedy, Eva A. Sandberg, Warren S. Ehrenfeld, Jesse M. TI A survey of modified rapid-sequence induction and intubation in Canadian academic centers SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter C1 [Bulka, Catherine M.; Sandberg, Warren S.; Ehrenfeld, Jesse M.] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37212 USA. [Cassedy, Eva A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Bulka, CM (reprint author), Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37212 USA. EM catherine.m.bulka@vanderbilt.edu OI Ehrenfeld, Jesse/0000-0003-3427-0140; Sandberg, Warren/0000-0002-9246-777X NR 3 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 2013 VL 25 IS 6 BP 515 EP 516 DI 10.1016/j.jclinane.2013.03.016 PG 2 WC Anesthesiology SC Anesthesiology GA 255FI UT WOS:000327224400017 PM 24008190 ER PT J AU Mtonga, P Masamba, L Milner, D Shulman, LN Nyirenda, R Mwafulirwa, K AF Mtonga, P. Masamba, L. Milner, D. Shulman, L. N. Nyirenda, R. Mwafulirwa, K. TI Biopsy case mix and diagnostic yield at a Malawian central hospital SO MALAWI MEDICAL JOURNAL LA English DT Article ID CANCER; POPULATION; TRENDS; BURDEN AB Cancer is a major disease burden worldwide resulting in high morbidity and mortality. It is the leading cause of mortality in developed countries and is one of the three leading causes of death for adults in developing countries. Pathological examination of tissue biopsies with histological confirmation of a correct cancer diagnosis is central to cancer care. Without an accurate and specific pathologic diagnosis, effective treatment cannot be planned or delivered. In addition, there are marked geographical variations in incidence of cancer overall, and of the specific cancers seen. Much of the published literature on cancer incidence in developing countries reflects gross estimates and may not reflect reality. Performing baseline studies to understand these distributions lays the groundwork for further research in this area of cancer epidemiology. Our current study surveys and ranks cancer diagnoses by individual anatomical site at Queen Elizabeth Central Hospital (QECH) which is the largest teaching and referral hospital in Malawi. A retrospective study was conducted reviewing available pathology reports over a period of one full year from January 2010 to December 2010 for biopsies from patients suspected clinically of having cancer. There were 544 biopsies of suspected cancer, taken from 96 anatomical sites. The oesophagus was the most common biopsied site followed by breast, bladder, bone, prostate, bowel, and cervical lymph node. Malignancies were found in biopsies of the oesophagus biopsies (squamous cell carcinoma, 65.1%; adenocarcinoma, 11.6%), breast (57.5%), bladder (squamous cell carcinoma, 53.1%) and stomach (37.6%). Our study demonstrates that the yield of biopsy for clinically suspected malignancy was greater than 50% for the 11 most common sites and provides a current survey of cancer types by site present in the population reporting to our hospital. C1 [Mtonga, P.; Nyirenda, R.; Mwafulirwa, K.] QECH, Blantyre, Malawi. [Masamba, L.; Mwafulirwa, K.] Univ Malawi, QECH, Coll Med, Zomba, Malawi. [Milner, D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shulman, L. N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Masamba, L (reprint author), Univ Malawi, QECH, Coll Med, Zomba, Malawi. EM leomasamba@yahoo.co.uk NR 12 TC 2 Z9 2 U1 0 U2 1 PU MED COLL MALAWI PI CHICHIRI PA MALAWAI MEDICAL JOURNAL, PRIVATE BAG 360, CHICHIRI, BLANTYRE 3 00000, MALAWI SN 1995-7262 EI 1995-7270 J9 MALAWI MED J JI Malawi Med. J. PD SEP PY 2013 VL 25 IS 3 BP 62 EP 64 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 252LQ UT WOS:000327006600002 PM 24358421 ER PT J AU Aspinall, SL Zhao, XH Good, CB Stone, RA Smith, KJ Cunningham, FE AF Aspinall, Sherrie L. Zhao, Xinhua Good, Chester B. Stone, Roslyn A. Smith, Kenneth J. Cunningham, Francesca E. TI FDA Warning and Removal of Rosiglitazone From VA National Formulary SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CARDIOVASCULAR EVENTS; DIABETES-MELLITUS; RISK; PIOGLITAZONE; METAANALYSIS; OUTCOMES; IMPACT; CARE AB Objectives: To describe changes in rosiglitazone prescribing following the US Food and Drug Administration (FDA) warning of potentially increased risk of myocardial infarction and removal from the Department of Veterans Affairs National Formulary (VANF), assess patient-level factors associated with rosiglitazone discontinuation, and evaluate changes in glucose control. Study Design: Historical cohort. Methods: Veterans with an active outpatient prescription for rosiglitazone on April 1, 2007, were followed until June 30, 2008. Incidence rate ratios (IRRs) of rosiglitazone discontinuation were compared over time using Poisson methods. We identified patient-level factors associated with stopping rosiglitazone using multivariable Poisson regression and compared glycated hemoglobin (A1C) values across time among patients who discontinued/continued rosiglitazone using linear mixed models. Results: Of 95,539 veterans with an active outpatient rosiglitazone prescription, 86.7% discontinued rosiglitazone. Discontinuation rates increased significantly after the FDA warning, with IRRs from 1.6 to 1.8. After removal from the VANF, rosiglitazone discontinuation rates again increased significantly. Discontinuing rosiglitazone was associated with the FDA warning, removal from the VANF, female sex, black race, Hispanic ethnicity, comorbidity,A1C greater than 9%, and use of rosiglitazone as first- or second-line therapy. Among patients who did and did not receive a replacement medication, the mean changes in A1C from baseline were 0.12% and 0.46%, respectively. for those who continued rosiglitazone, the mean change in A1C was 0.02%. Conclusion: The rosiglitazone discontinuation rate increased following the FDA warning and increased further following removal of rosiglitazone from the VANE Glucose control may have declined among those who discontinued rosiglitazone. C1 [Aspinall, Sherrie L.; Zhao, Xinhua; Good, Chester B.; Cunningham, Francesca E.] VA Ctr Medicat Safety, Hines, IL USA. [Aspinall, Sherrie L.; Zhao, Xinhua; Good, Chester B.; Stone, Roslyn A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Aspinall, Sherrie L.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Smith, Kenneth J.] Univ Pittsburgh, Div Clin Modeling & Decis Sci, Pittsburgh, PA USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM sherrie.aspinall@va.gov NR 21 TC 6 Z9 6 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2013 VL 19 IS 9 BP 748 EP 758 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 244WF UT WOS:000326420200005 PM 24304257 ER PT J AU Oyer, SL Nagel, W Mulligan, JK AF Oyer, Samuel L. Nagel, Whitney Mulligan, Jennifer K. TI Differential expression of adhesion molecules by sinonasal fibroblasts among control and chronic rhinosinusitis patients SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID NASAL POLYPOSIS; EOSINOPHIL INFILTRATION; TNF-ALPHA; ENDOTHELIAL-CELLS; CHRONIC SINUSITIS; LUNG FIBROBLASTS; INFLAMMATION; BUDESONIDE; VCAM-1; ICAM-1 AB Background: Chronic rhinosinusitis (CRS) is characterized by inflammatory cell migration into sinus tissue with resultant inflammation fueled by a milieu of cytokines. Fibroblasts may contribute to inflammation through expression of leukocyte adhesion molecules such as vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM). VCAM attracts eosinophils and mast cells contributing to Th2 skewing, and ICAM attracts neutrophils and to a lesser degree, eosinophils, and contributes to mixed Th1/Th2 skewing. The purpose of this study was to compare sinus fibroblast adhesion molecule expression ex vivo among CRS subtypes and in vitro after cytokine stimulation. Methods: Sinus biopsy specimens were taken from control patients (n = 13), CRS without nasal polyposis (CRSsNP, n = 6), and CRS with nasal polyposis (CRSwNP, n = 15). Ex vivo levels of VCAM and ICAM were measured by flow cytometry from single cell suspensions of tissue biopsy specimens. Changes in VCAM and ICAM expression to cytokine exposure were assessed using in vitro cultured sinonasal fibroblasts treated with tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, or interferon (IFN)-gamma. Results: Ex vivo VCAM expression was lowest in controls, higher in CRSsNP, and highest in CRSwNP. In vitro stimulation with TNF-alpha and IL-4, but not IFN-gamma, increased VCAM among CRSsNP, while expression in CRSwNP remained elevated with all treatments except IFN-gamma. Ex vivo ICAM expression was elevated in both CRS subtypes. In vitro stimulation with TNF-alpha and IFN-gamma, but not IL-4, increased ICAM expression in all patients with the largest effects among the CRSsNP subgroup. Conclusion: Sinonasal fibroblast expression of adhesion molecules in sinusitis varies by disease state and is selectively influenced by exposure to inflammatory cytokines. C1 [Oyer, Samuel L.; Nagel, Whitney; Mulligan, Jennifer K.] Med Univ S Carolina, Div Rhinol & Sinus Surg, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Oyer, Samuel L.; Nagel, Whitney; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Ralph H Johnson Vet Affairs Med Ctr, Dept Surg, Res Serv, Charleston, SC USA. RP Mulligan, JK (reprint author), MSC 550,135 Rutledge Ave, Charleston, SC 29425 USA. EM konopa@musc.edu FU American Rhinologic Society as part of the Centralized Otolaryngology Research Efforts (CORE) Grants program; Flight Attendant Medical Research Institutes FX Funded by a grant to SL Oyer from the American Rhinologic Society as part of the Centralized Otolaryngology Research Efforts (CORE) Grants program, and a grant to JK Mulligan from the Flight Attendant Medical Research Institutes. The remaining author has no conflicts of interest to declare pertaining to this article NR 28 TC 5 Z9 5 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD SEP-OCT PY 2013 VL 27 IS 5 BP 381 EP 386 DI 10.2500/ajra.2013.27.3934 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 249EL UT WOS:000326759700014 PM 24119601 ER PT J AU Reeves, ST Finley, AC Skubas, NJ Swaminathan, M Whitley, WS Glas, KE Hahn, RT Shanewise, JS Adams, MS Shernan, SK AF Reeves, Scott T. Finley, Alan C. Skubas, Nikolaos J. Swaminathan, Madhav Whitley, William S. Glas, Kathryn E. Hahn, Rebecca T. Shanewise, Jack S. Adams, Mark S. Shernan, Stanton K. CA Amer Soc Echocardiography Soc Cardiovascular Anesthesiologis TI Basic Perioperative Transesophageal Echocardiography Examination: A Consensus Statement of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists SO ANESTHESIA AND ANALGESIA LA English DT Article ID BLUNT CHEST TRAUMA; TRANS-ESOPHAGEAL ECHOCARDIOGRAPHY; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; CARDIAC SURGICAL-PATIENTS; CAPILLARY WEDGE PRESSURE; PARADOXICAL AIR-EMBOLISM; ACUTE PULMONARY-EMBOLISM; CRITICALLY ILL PATIENTS; INTENSIVE-CARE-UNIT; TASK-FORCE C1 [Reeves, Scott T.; Finley, Alan C.] Med Univ S Carolina, New York, NY USA. [Skubas, Nikolaos J.] Weill Cornell Med Coll, New York, NY USA. [Swaminathan, Madhav] Duke Univ, Durham, NC USA. [Shernan, Stanton K.] Harvard Univ, Brighams & Womens Hosp, Sch Med, Boston, MA USA. [Whitley, William S.; Glas, Kathryn E.] Emory Univ, Atlanta, GA 30322 USA. [Hahn, Rebecca T.; Shanewise, Jack S.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Adams, Mark S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reeves, ST (reprint author), Med Univ S Carolina, New York, NY USA. NR 88 TC 17 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2013 VL 117 IS 3 BP 543 EP 558 DI 10.1213/ANE.0b013e3182a00616 PG 16 WC Anesthesiology SC Anesthesiology GA 248JJ UT WOS:000326695200002 PM 23966648 ER PT J AU Henke, VG Bateman, BT Leffert, LR AF Henke, Vanessa G. Bateman, Brian T. Leffert, Lisa R. TI Spinal Anesthesia in Severe Preeclampsia SO ANESTHESIA AND ANALGESIA LA English DT Review ID CESAREAN DELIVERY; EPIDURAL-ANESTHESIA; REGIONAL-ANESTHESIA; GENERAL-ANESTHESIA; BLOOD-FLOW; SECTION; WOMEN; PREGNANCY; RISK; HYPOTENSION AB Spinal anesthesia is widely regarded as a reasonable anesthetic option for cesarean delivery in severe preeclampsia, provided there is no indwelling epidural catheter or contraindication to neuraxial anesthesia. Compared with healthy parturients, those with severe preeclampsia experience less frequent, less severe spinal-induced hypotension. In severe preeclampsia, spinal anesthesia may cause a higher incidence of hypotension than epidural anesthesia; however, this hypotension is typically easily treated and short lived and has not been linked to clinically significant differences in outcomes. In this review, we describe the advantages and limitations of spinal anesthesia in the setting of severe preeclampsia and the evidence guiding intraoperative hemodynamic management. C1 [Henke, Vanessa G.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Henke, Vanessa G.; Bateman, Brian T.; Leffert, Lisa R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Henke, VG (reprint author), Ronald Reagan UCLA Med Ctr, UCLA Dept Anesthesiol, 757 Westwood Plaza,Suite 3325, Los Angeles, CA 90095 USA. EM vanessagiselle@gmail.com NR 55 TC 12 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2013 VL 117 IS 3 BP 686 EP 693 DI 10.1213/ANE.0b013e31829eeef5 PG 8 WC Anesthesiology SC Anesthesiology GA 248JJ UT WOS:000326695200021 PM 23868886 ER PT J AU Chung, J Issadore, D Ullal, A Lee, K Weissleder, R Lee, H AF Chung, Jaehoon Issadore, David Ullal, Adeeti Lee, Kyungheon Weissleder, Ralph Lee, Hakho TI Rare cell isolation and profiling on a hybrid magnetic/size-sorting chip SO BIOMICROFLUIDICS LA English DT Article ID CIRCULATING TUMOR-CELLS; BREAST-CANCER; METASTASIS; CAPTURE; EGFR AB We present a hybrid magnetic/size-sorting (HMSS) chip for isolation and molecular analyses of circulating tumor cells (CTCs). The chip employs both negative and positive cell selection in order to provide high throughput, unbiased CTC enrichment. Specifically, the system utilizes a self-assembled magnet to generate high magnetic forces and a weir-style structure for cell sorting. The resulting device thus can perform multiple functions, including magnetic depletion, size-selective cell capture, and on-chip molecular staining. With such capacities, the HMSS device allowed one-step CTC isolation and single cell detection from whole blood, tested with spiked cancer cells. The system further facilitated the study of individual CTCs for heterogeneity in molecular marker expression. (C) 2013 AIP Publishing LLC. C1 [Chung, Jaehoon; Issadore, David; Ullal, Adeeti; Lee, Kyungheon; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu RI Issadore, David/L-8451-2014 FU NHLBI [R01-HL113156, HHSN268201000044C, T32CA79443]; NIBIB [R01-EB010011, R01-EB00462605] FX We thank V. Cortez-Remano, A. Newton, and F. Pucci for help with flow cytometry; H. Shao, H. Chung, A. Ghazani and C. Castro for helpful discussions. This work was supported in part by NHLBI grants R01-HL113156 (H. L.), NIBIB R01-EB010011 (R. W.), R01-EB00462605 (R. W.), NHLBI contract HHSN268201000044C (R. W.), and T32CA79443 (R.W.). NR 36 TC 20 Z9 21 U1 5 U2 40 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1932-1058 J9 BIOMICROFLUIDICS JI Biomicrofluidics PD SEP PY 2013 VL 7 IS 5 AR 054107 DI 10.1063/1.4821923 PG 9 WC Biochemical Research Methods; Biophysics; Nanoscience & Nanotechnology; Physics, Fluids & Plasmas SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics; Physics GA 250TK UT WOS:000326877600009 PM 24404070 ER PT J AU Erim, T Shiroky, J Pleskow, DK AF Erim, Tolga Shiroky, Jennifer Pleskow, Douglas K. TI Cholangioscopy: the biliary tree never looked so good! SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE biliary disease; cholangioscopy; direct visualization; ERCP ID DIRECT PERORAL CHOLANGIOSCOPY; DOUBLE-BALLOON ENTEROSCOPE; ULTRA-SLIM GASTROSCOPE; ALTERED GI ANATOMY; BILE-DUCT STONES; PRIMARY SCLEROSING CHOLANGITIS; CONFOCAL LASER ENDOMICROSCOPY; PAPILLARY MUCINOUS NEOPLASM; ARGON PLASMA COAGULATION; UPPER ENDOSCOPE AB Purpose of reviewEndoscopists have long awaited advances in the equipment and techniques for cholangiopancreatoscopy. Since the turn of the millennium, endoscopists have witnessed an explosion in the development and refinement of the capabilities of cholangioscopes as they move from being almost exclusive to tertiary care academic settings to a wider range of practices. Recent findingsStudies have tested and constructively critiqued the procedure, hoping to increase the success rate of diagnostic and therapeutic interventions. Many have found significant improvement upon the limitations of radiographic imaging in diagnosing diseases and achieving full clearance of biliary stones. Image quality has improved with a range of features. However, most of these still need to be studied further. The addition of balloon catheters and overtubes has improved stability and access to the biliary ducts, but comes with complications that need to be studied further. SummaryAlthough we still have improvements to yearn for, the future looks bright. As endoscopists continue their commitment to the promise of direct visualization of the biliary trees and the complementary tools for diagnosis and treatment, we are continuing to raise quality of care for patients with complicated biliary diseases. C1 [Erim, Tolga; Shiroky, Jennifer] Cleveland Clin, Dept Gastroenterol & Hepatol, Weston, FL USA. [Pleskow, Douglas K.] Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02215 USA. RP Pleskow, DK (reprint author), BIDMC, Div Gastroenterol, GI West,110 Francis St,Suite 8E, Boston, MA 02215 USA. EM dpleskow@bidmc.harvard.edu OI Pleskow, Douglas/0000-0003-0092-9496 NR 78 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 EI 1531-7056 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2013 VL 29 IS 5 BP 501 EP 508 DI 10.1097/MOG.0b013e3283640f4b PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247CI UT WOS:000326591300003 PM 23852142 ER PT J AU Brugge, WR AF Brugge, William R. TI Endoscopic approach to the diagnosis and treatment of pancreatic disease SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE chronic pancreatitis; endoscopic retrograde cholangio-pancreatography; endoscopic ultrasound; fine needle aspiration; intraductal papillary mucinous neoplasm ID RECURRENT ACUTE-PANCREATITIS; EUS-GUIDED FNA; RETROGRADE CHOLANGIOPANCREATOGRAPHY; BILIARY PANCREATITIS; MASS LESIONS; DUCT STONES; ULTRASOUND; SECRETIN; DRAINAGE; SPHINCTEROTOMY AB Purpose of reviewThe purpose of this review is to examine the recent developments in the use of endoscopic retrograde cholangio-pancreatography (ERCP) and endoscopic ultrasound (EUS) in the management of patients with pancreatic-biliary disease. Recent findingsThe use of ERCP to guide selective placement of pancreatic sphincterotomes, stone extraction balloons, and stents enables clinicians to treat pancreatic sphincteric and ductal disorders. Pancreatic stones are a remediable cause of recurrent pancreatitis and small calculi can be easily removed. The gold standard for the diagnosis of pancreas divisum remains ERCP and sphincterotomy is highly effective in the treatment of relapsing pancreatitis. Intraductal papillary mucinous neoplasms are the most common pancreatic malignancy and ERCP, as well as EUS can identify and sample the solid and cystic lesions. Mural nodules can be detected and sampled effectively by EUS-fine needle aspiration (FNA). The sensitivity of EUS-FNA for pancreatic adenocarcinoma is excellent (more than 85%). Although cyst fluid carcinoembryonic antigen is a very good marker for the presence of a mucinous cystic lesion, it is not an indicator of malignancy. SummaryIn summary, ERCP and EUS are important tools for the management of benign and malignant lesions of the pancreas. C1 [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Blake 452C, Boston, MA 02114 USA. EM WBrugge@partners.org FU RedPath; Asuragen; Cellgene FX Research grants from RedPath, Asuragen, and Cellgene. NR 45 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 EI 1531-7056 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2013 VL 29 IS 5 BP 559 EP 565 DI 10.1097/MOG.0b013e3283639342 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247CI UT WOS:000326591300011 PM 23872485 ER PT J AU Koseoglu, S Flaumenhaft, R AF Koseoglu, Secil Flaumenhaft, Robert TI Advances in platelet granule biology SO CURRENT OPINION IN HEMATOLOGY LA English DT Review DE exocytosis; granules; platelets ID ALPHA-GRANULE; MYOCARDIAL-INFARCTION; MOLECULAR-MECHANISMS; RENAL DYSFUNCTION; MEMBRANE-FUSION; GENE VARIANTS; PROTEIN DRP1; SYNTAXIN 4; SECRETION; RELEASE AB Purpose of reviewThis review will provide an overview of several recent advances in the field of platelet granule biology.Recent findingsThe past few years have witnessed a substantial evolution in our knowledge of platelet granules based on a number of discoveries and new experimental approaches. This article will cover recent studies in five areas. First, the vesicle trafficking pathways responsible for -granule formation are beginning to be assembled as a result of the characterization of patients with -granule deficiencies. Second, a revision of our understanding of which SNARE isoforms mediate platelet granule exocytosis has occurred following evaluation of patients with defects in platelet granule exocytosis and the generation of mice lacking specific SNAREs. Third, investigators have begun to establish how cargos are segregated among -granules and determine whether or not different -granule subpopulations exist in platelets. Fourth, an unanticipated role for -granules in platelet spreading has been identified. Fifth, single-cell amperometry has revealed secretion kinetics with submillisecond temporal resolution enabling evaluation of the molecular control of the platelet fusion pore.SummaryThese new observations reveal a previously unappreciated complexity to platelet granule formation and exocytosis and challenge our earlier notions of how these granules are organized within platelets and contribute to the multitude of physiological activities in which platelets function. C1 [Koseoglu, Secil; Flaumenhaft, Robert] Harvard Univ, Sch Med, Dept Med, Div Hemostasis & Thrombosis,BIDMC, Boston, MA USA. RP Flaumenhaft, R (reprint author), Beth Israel Deaconess Med Ctr, Ctr Life Sci, Room 939,3 Blackfan Circle, Boston, MA 02215 USA. EM rflaumen@bidmc.harvard.edu FU NIH [HL112809]; American Heart Association FX The authors would like to acknowledge the many other important recent studies in the area of platelet granule biology that were not mentioned in this brief review owing to space restrictions. This work was supported by NIH HL112809 (R.F.) and an Established Investigator Award (R.F.) from the American Heart Association. NR 60 TC 26 Z9 26 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD SEP PY 2013 VL 20 IS 5 BP 464 EP 471 DI 10.1097/MOH.0b013e3283632e6b PG 8 WC Hematology SC Hematology GA 248ZS UT WOS:000326746200010 PM 23839294 ER PT J AU Penson, RT Dizon, DS Birrer, MJ AF Penson, Richard T. Dizon, Don S. Birrer, Michael J. TI Clear cell cancer of the ovary SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE angiogenesis; clinical trials; cytokines; ovarian clear cell cancer ID EPITHELIAL OVARIAN; CARCINOMA; CHEMOTHERAPY; PATHOGENESIS; HISTOLOGY; TRIAL AB Purpose of reviewRecent discoveries have demonstrated that ovarian cancer is actually composed of multiple separate diseases. Clear cell cancer is an important example. This review will describe the unique biology of clear cell carcinoma, its novel molecular features, and the recent translation of this into new therapeutic approaches.Recent findingsClear cell cancer of the ovary is now recognized as a unique disease. Recent work has shown that a subset of clear cell cancers evolve from endometriosis. The oxidative stress conditions found within endometriotic lesions are likely to contribute to the transformation process. Molecular alterations within clear cell cancers include unique cytokine expression patterns and c-met amplification. Clear cell-specific clinical trials based upon these biologic discoveries have been designed and are presently active.SummaryThese studies provide substantive support for a unique clinical management of clear cell cancer of the ovary. Future research will exploit the molecular pathways identified in these tumors in an effort to provide more effective therapies. Presently, agents that target angiogenesis or cellular metabolism would be reasonable therapeutic approaches to these tumors. C1 [Penson, Richard T.; Dizon, Don S.; Birrer, Michael J.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Yawkey 9-072,55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org NR 25 TC 7 Z9 8 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD SEP PY 2013 VL 25 IS 5 BP 553 EP 557 DI 10.1097/CCO.0b013e328363e0c7 PG 5 WC Oncology SC Oncology GA 247GR UT WOS:000326605600015 PM 23942300 ER PT J AU Weinberg, I Jaff, MR AF Weinberg, Ido Jaff, Michael R. TI Treating large pulmonary emboli: do the guidelines guide us? SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE guidelines; pulmonary embolism; thrombolysis; venous thromboembolism ID RIGHT-VENTRICULAR DYSFUNCTION; PROGNOSTIC VALUE; PLASMINOGEN-ACTIVATOR; RANDOMIZED-TRIAL; SEVERITY INDEX; VENOUS THROMBOEMBOLISM; MEMBRANE-OXYGENATION; COMPUTED-TOMOGRAPHY; SURGICAL-TREATMENT; BOLUS ALTEPLASE AB Purpose of reviewThe diagnosis and management of patients with large pulmonary emboli can be confusing. This review will summarize available data and suggest the areas of certainty and uncertainty in the treatment of these patients.Recent findingsPulmonary emboli can be stratified according to patient prognosis. Risk-stratification of patients with submassive pulmonary emboli is still lacking. Similarly, although the treatment of low-risk pulmonary embolism is well established, and there is consensus regarding systemic thrombolysis for unstable patients with pulmonary embolism, the management of patients with submassive pulmonary embolism is still a matter of debate. The role of novel approaches such as low-dose thrombolysis, catheter-directed therapies and advanced cardiopulmonary support is yet to be determined. Although some patients in skilled centers may benefit from pulmonary embolectomy, patient selection has yet to be refined.SummaryThe treatment of massive and submassive pulmonary embolism has yet to be standardized. The complexity in choosing appropriate treatments for these patients is due to the lack of high-quality data compounded by an expanding arsenal of therapeutic options. C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 905, Boston, MA 02114 USA. EM mjaff@partners.org NR 66 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 EI 1531-6971 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD SEP PY 2013 VL 19 IS 5 BP 413 EP 421 DI 10.1097/MCP.0b013e3283642a63 PG 9 WC Respiratory System SC Respiratory System GA 247BC UT WOS:000326587100002 PM 23884294 ER PT J AU Gray, PJ Shipley, WU Efstathiou, JA Zietman, AL AF Gray, Phillip J. Shipley, William U. Efstathiou, Jason A. Zietman, Anthony L. TI Recent advances and the emerging role for chemoradiation in nonmuscle invasive bladder cancer SO CURRENT OPINION IN UROLOGY LA English DT Review DE biomarkers; chemoradiation; MRE11; nonmuscle invasive bladder cancer ID TRANSITIONAL-CELL CARCINOMA; BACILLUS-CALMETTE-GUERIN; PROSPECTIVE RANDOMIZED-TRIAL; RADICAL CYSTECTOMY; UROTHELIAL CARCINOMA; NEOADJUVANT CHEMOTHERAPY; TRANSURETHRAL RESECTION; INTRAVESICAL THERAPY; PATHOLOGICAL STAGE; TREATMENT OPTIONS AB Purpose of reviewThe management of nonmuscle invasive bladder cancer (NMIBC) recurrent after bacillus Calmette-Guerin therapy is complex and further complicated by high numbers of patients who are not candidates for cystectomy. This article reviews data supporting the use of chemoradiation in NMIBC and discusses emerging biomarkers of treatment response.Recent findingsRadiotherapy, especially when combined with chemotherapy, has shown great promise for treating bladder cancer. Recent studies have identified that many patients with bladder cancer do not receive potentially curative therapies. Many such patients are elderly or infirm and represent an unmet need for curative therapeutic alternatives to radical cystectomy. Although radiotherapy alone does not appear superior to intravesical therapy in NMIBC, at least one series with long-term follow-up has shown excellent results in patients treated with radiation and concurrent chemotherapy. A clinical trial investigating the role for chemoradiation in T1 disease that has recurred is underway. Biomarkers able to predict radiotherapy response may allow for personalized therapy in the near future.SummaryChemoradiation is an emerging treatment option for selected patients with NMIBC. Prospective validation of currently identified biomarkers is needed along with further research to identify which patients may benefit the most from such therapy. C1 [Gray, Phillip J.; Shipley, William U.; Efstathiou, Jason A.; Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Gray, Phillip J.] Harvard Radiat Oncol Program, Boston, MA USA. RP Gray, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM pjgray@partners.org NR 47 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 EI 1473-6586 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD SEP PY 2013 VL 23 IS 5 BP 429 EP 434 DI 10.1097/MOU.0b013e328363de04 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 248YW UT WOS:000326743400008 PM 23851382 ER PT J AU Bellmunt, J Pons, F Orsola, A AF Bellmunt, Joaquim Pons, Francesc Orsola, Anna TI Molecular determinants of response to cisplatin-based neoadjuvant chemotherapy SO CURRENT OPINION IN UROLOGY LA English DT Review DE bladder-invasive cancer; gene expression profiling; neodjuvant chemotherapy; prognostic markers ID ADVANCED BLADDER-CANCER; TRANSITIONAL-CELL CARCINOMA; MESSENGER-RNA EXPRESSION; PROGNOSTIC VALUE; GENE-EXPRESSION; TUMOR PROGRESSION; ONCOLOGY-GROUP; P53; RESISTANCE; CYSTECTOMY AB Purpose of reviewNeoadjuvant chemotherapy followed by cystectomy improves survival compared with surgery alone. To prevent overtreatment is of outmost importance to define molecular predictors of response for patient selection. We present the currently available data outlining a variety of potential markers to aid for a personalized decision-making process.Recent findingsApart from p53, other markers of cell cycle regulation and apoptosis such as p21WAF1/CIP1 (p21) gene, Bcl-2, mouse double minute-2 and pRB have also been related to survival. The clinical relevance of epidermal growth factor receptor and HER2 expression has also been investigated with no success. Regarding Ki67, overexpressing tumors may potentially benefit from neoadjuvant therapy and conversely overexpression of vascular endothelial growth factor and bFGF have been linked to resistance to cisplatin-induced apoptosis. The role of multidrug resistance gene 1 and excision repair cross-complementing rodent repair deficiency complementation group 1 supports that enhanced DNA repair in the tumor decreases the benefit of platinum-based treatment. A 20-gene expression model has shown to predict lymph node involvement, helping on decision-making. A gene expression profiling has been proposed as predictive for response to neoadjuvant chemotherapy.SummaryPredictive markers will eventually aid in the selection of patients that most likely benefit from preoperative treatment. In the coming years, a panel of markers will become available to achieve the predicted goal. C1 [Bellmunt, Joaquim] Univ Hosp del Mar, Lab Recerca IMIM, Barcelona, Spain. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02215 USA. [Pons, Francesc] Hosp del Mar, Dept Med Oncol, Barcelona, Spain. [Orsola, Anna] Hosp Valle De Hebron, Dept Urol, Barcelona, Spain. RP Bellmunt, J (reprint author), Univ Hosp del Mar, Lab Recerca IMIM, Barcelona, Spain. EM Joaquim_bellmunt@dfci.harvard.edu RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; orsola, anna/0000-0001-8124-4231 FU PiereFabre; Pfizer; SanofiAventis FX J.B.; lectures fees and ad-boards for PiereFabre, Pfizer, and SanofiAventis. NR 35 TC 8 Z9 8 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 EI 1473-6586 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD SEP PY 2013 VL 23 IS 5 BP 466 EP 471 DI 10.1097/MOU.0b013e328363de67 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 248YW UT WOS:000326743400013 PM 23851383 ER PT J AU Aerts, HJ AF Aerts, H. J. TI Radiomics: Promoting evidence through image features from radiographic images SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Aerts, H. J.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 302 BP S69 EP S69 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843600253 ER PT J AU Bellmunt, J Yu, MK Kheoh, T Taplin, ME Davis, ID Schnjvers, D Protheroe, A Molina, A De Bono, JS Scher, HI AF Bellmunt, J. Yu, M. K. Kheoh, T. Taplin, M. E. Davis, I. D. Schnjvers, D. Protheroe, A. Molina, A. De Bono, J. S. Scher, H. I. TI Impact of prior antiandrogen exposure on clinical outcomes in patients (pts) receiving abiraterone acetate (AA): Results from a randomized study (COU-AA-301) in metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel (D) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Bellmunt, J.] Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA 02115 USA. [Yu, M. K.] Janssen Res & Dev, WC Clin Oncol, Los Angeles, CA USA. [Kheoh, T.] Janssen Res & Dev, Biostat & Programming, Los Angeles, CA USA. [Taplin, M. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Davis, I. D.] Monash Univ, Clayton, Vic 3800, Australia. [Davis, I. D.] Eastern Hlth, Eastern Hlth Clin Sch, Melbourne, Vic, Australia. [Schnjvers, D.] ZNA Middelheim Oncol Clin, Antwerp, Belgium. [Protheroe, A.] Churchill Hosp, Oxford OX3 7LJ, England. [Molina, A.] Janssen Res & Dev, Oncol, Los Angeles, CA USA. [De Bono, J. S.] Inst Canc Res, Sutton, Surrey, England. [De Bono, J. S.] Royal Marsden Hosp, Urol Unit, Sutton, Surrey, England. [De Bono, J. S.] Drug Dev Unit, Sutton, Surrey, England. [Scher, H. I.] Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, Genitourinary Oncol Serv, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2897 BP S695 EP S695 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604259 ER PT J AU Bellmunt, J AF Bellmunt, J. TI Biomarkers for neoadjuvant chemotherapy in bladder cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Bellmunt, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellmunt, J.] IMIM Barcelona, Med Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 125 BP S29 EP S30 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843600102 ER PT J AU Blackhall, F Shaw, AT Janne, PA Kim, DW Wilner, KD Schnell, P Polli, A Besse, B AF Blackhall, F. Shaw, A. T. Jaenne, P. A. Kim, D. W. Wilner, K. D. Schnell, P. Polli, A. Besse, B. TI Crizotinib safety profile in elderly and non-elderly patients (pts) with advanced ALK plus non-small cell lung cancer (NSCLC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Blackhall, F.] Christie Hosp NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England. [Shaw, A. T.] Massachusetts Gen Hosp, Dept Thorac Oncol, Boston, MA 02114 USA. [Jaenne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Kim, D. W.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Wilner, K. D.] Pfizer Oncol, Med Oncol, La Jolla, CA USA. [Schnell, P.] Pfizer Oncol, Med Oncol, New York, NY USA. [Polli, A.] Pfizer Oncol, Stat, Milan, Italy. [Besse, B.] Inst Gustave Roussy, Dept Canc Med, Villejuif, France. RI Blackhall, Fiona/N-2186-2015 OI Blackhall, Fiona/0000-0001-8716-3395 NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3476 BP S821 EP S821 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605197 ER PT J AU Blackhall, F Hirsh, V Kim, DW Besse, B Nokihara, H Han, JY Wilner, K Reisman, A Iyer, S Shaw, A AF Blackhall, F. Hirsh, V. Kim, D. W. Besse, B. Nokihara, H. Han, J. Y. Wilner, K. Reisman, A. Iyer, S. Shaw, A. TI Impact of crizotinib on patient-reported general health status compared with single-agent chemotherapy in a phase III study of advanced ALK-positive non-small cell lung cancer (NSCLC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Blackhall, F.] Christie Hosp NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England. [Hirsh, V.] McGill Univ, Dept Oncol, Ctr Hlth, Montreal, PQ, Canada. [Kim, D. W.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Besse, B.] Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Nokihara, H.] Natl Canc Ctr, Div Internal Med, Tokyo, Japan. [Han, J. Y.] Natl Canc Ctr, Ctr Lung Canc, Goyang, South Korea. [Wilner, K.] Pfizer Oncol, Med Oncol, La Jolla, CA USA. [Reisman, A.] Pfizer Specialty Care, Stat, New York, NY USA. [Iyer, S.] Pfizer Oncol, Hlth Econ & Outcomes, New York, NY USA. [Shaw, A.] Massachusetts Gen Hosp, Dept Thorac Oncol, Boston, MA 02114 USA. RI Blackhall, Fiona/N-2186-2015 OI Blackhall, Fiona/0000-0001-8716-3395 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3412 BP S799 EP S800 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843605133 ER PT J AU Blackhall, F Hirsh, V Kim, DW Besse, B Nokihara, H Han, JY Wilner, K Reisman, A Iyer, S Shaw, A AF Blackhall, F. Hirsh, V. Kim, D. W. Besse, B. Nokihara, H. Han, J. Y. Wilner, K. Reisman, A. Iyer, S. Shaw, A. TI Impact of crizotinib on patient-reported symptoms and global quality of life (QoL) compared with chemotherapy in a phase III study of advanced alk-positive non-small cell lung cancer (NSCLC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Blackhall, F.] Christie Hosp NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England. [Hirsh, V.] McGill Univ, Dept Oncol, Ctr Hlth, Montreal, PQ, Canada. [Kim, D. W.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Besse, B.] Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Nokihara, H.] Natl Canc Ctr, Div Internal Med, Tokyo, Japan. [Han, J. Y.] Natl Canc Ctr, Ctr Lung Canc, Goyang, South Korea. [Wilner, K.] Pfizer Oncol, Med Oncol, La Jolla, CA USA. [Reisman, A.] Pfizer Specialty Care, Stat, New York, NY USA. [Iyer, S.] Pfizer Oncol, Hlth Econ & Outcomes, New York, NY USA. [Shaw, A.] Massachusetts Gen Hosp, Dept Thorac Oncol, Boston, MA 02114 USA. RI Blackhall, Fiona/N-2186-2015 OI Blackhall, Fiona/0000-0001-8716-3395 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3400 BP S795 EP S795 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605121 ER PT J AU Blay, J Casali, PG Reichardt, P Kang, YK Rutkowski, P Gelderblom, H Hohenberger, P Kappeler, C Kuss, I Demetri, GD AF Blay, J. Casali, P. G. Reichardt, P. Kang, Y. K. Rutkowski, P. Gelderblom, H. Hohenberger, P. Kappeler, C. Kuss, I. Demetri, G. D. TI Time course of adverse events in the phase III GRID study of regorafenib in patients with metastatic gastrointestinal stromal tumors (GIST) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Blay, J.] Ctr Reg Leon Berard, INSERM, U590, Lyon, France. [Casali, P. G.] Ist Nazl Tumori, Adult Mesenchymal Tumour Med Oncol Unit, I-20133 Milan, Italy. [Reichardt, P.] HELIOS Klinikum Berlin Buch, Interdisciplinary Oncol Sarcoma Ctr Berlin Brande, Berlin, Germany. [Kang, Y. K.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, P.] Inst Oncol, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Gelderblom, H.] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Hohenberger, P.] Univ Mannheim, Med Ctr, Div Surg Oncol & Thorac Surg, D-68131 Mannheim, Germany. [Kappeler, C.] Bayer HealthCare, Global Clin Dev Clin Stat Europe, Berlin, Germany. [Kuss, I.] Bayer Pharma AG, Global Clin Dev Therapeut Area Oncol Ophthalmol &, Berlin, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Demetri, G. D.] Harvard Univ, Sch Med, Ludwig Ctr, Boston, MA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3827 BP S884 EP S885 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843605396 ER PT J AU Camidge, DR Bazhenova, L Salgia, R Weiss, GJ Langer, CJ Shaw, AT Narasimhan, NI Dorer, DJ Zhang, J Gettinger, SN AF Camidge, D. R. Bazhenova, L. Salgia, R. Weiss, G. J. Langer, C. J. Shaw, A. T. Narasimhan, N. I. Dorer, D. J. Zhang, J. Gettinger, S. N. TI Updated results of a first-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Camidge, D. R.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Bazhenova, L.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Salgia, R.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Weiss, G. J.] Scottsdale Healthcare, Virginia G Piper Canc Ctr Clin Trials, Scottsdale, AZ USA. [Langer, C. J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Shaw, A. T.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Gettinger, S. N.] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3401 BP S795 EP S795 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605122 ER PT J AU Chabner, B AF Chabner, B. TI Can drug approval keep pace with translational research in cancer? SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Chabner, B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 335 BP S76 EP S76 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843600277 ER PT J AU Chang, J Casali, PG Reichardt, P Kang, YK Blay, JY Wu, Y Odom, D Kuss, I Demetri, GD AF Chang, J. Casali, P. G. Reichardt, P. Kang, Y. K. Blay, J. Y. Wu, Y. Odom, D. Kuss, I. Demetri, G. D. TI Health-related quality of life (HRQoL) of patients with advanced gastrointestinal stromal tumors (GIST) treated with regorafenib (REG) vs placebo (P) in the phase III GRID trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Chang, J.] Bayer HealthCare Pharmaceut, Global Hlth Econ & Outcomes Res, Montville, NJ USA. [Casali, P. G.] Ist Nazl Tumori, Adult Mesenchymal Tumour Med Oncol Unit, I-20133 Milan, Italy. [Reichardt, P.] HELIOS Klinikum Berlin Buch, Interdisciplinary Oncol Sarcoma Ctr Berlin Brande, Berlin, Germany. [Kang, Y. K.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Blay, J. Y.] Ctr Leon Berard, Dept Medecine, French Sarcoma Grp, F-69373 Lyon, France. [Wu, Y.; Odom, D.] RTI Hlth Solut, Biostat, Durham, NC USA. [Kuss, I.] Bayer Pharma AG, Global Clin Dev Therapeut Area Oncol Ophthalmol &, Berlin, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Demetri, G. D.] Harvard Univ, Sch Med, Global Clin Dev Therapeut Area Oncol Ophthalmol &, Boston, MA USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3830 BP S886 EP S886 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605399 ER PT J AU Chau, I Passalacqua, R Zalcberg, JR Fuchs, CS Liepa, AM Hsu, Y Schwartz, JD Koshiji, M Tabernero, J AF Chau, I. Passalacqua, R. Zalcberg, J. R. Fuchs, C. S. Liepa, A. M. Hsu, Y. Schwartz, J. D. Koshiji, M. Tabernero, J. TI Tolerability and quality-of-life (QoL) results from the phase REGARD study: Ramucirumab versus placebo in patients with previously treated gastric or gastroesophageal junction (GEJ) adenocarcinoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Chau, I.] Royal Marsden Hosp, Dept Med, Sutton, Surrey, England. [Passalacqua, R.] Ist Ospitalieri Cremona, Div Med Oncol, Cremona, Italy. [Zalcberg, J. R.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Zalcberg, J. R.] Univ Melbourne, Div Hematol & Med Oncol, Melbourne, Vic, Australia. [Fuchs, C. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fuchs, C. S.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. [Liepa, A. M.] Eli Lilly & Co, Global Hlth Outcomes, Indianapolis, IN 46285 USA. [Hsu, Y.] ImClone Syst LLC, Global Stat Sci, Bridgewater, MA USA. [Schwartz, J. D.] ImClone Syst LLC, Global Med Sci, Bridgewater, MA USA. [Koshiji, M.] Eli Lilly & Co, Global Med Sci, Indianapolis, IN 46285 USA. [Tabernero, J.] Vall dHebron Univ Hosp, Barcelona, Spain. [Tabernero, J.] Univ Autonoma Barcelona, Dept Med Oncol, E-08193 Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2588 BP S615 EP S615 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604026 ER PT J AU Corcoran, RB Rothenberg, SM Piris, A Nazarian, RM Maheswaran, S Settleman, J Wargo, JA Flaherty, KT Haber, DA Engelman, JA AF Corcoran, R. B. Rothenberg, S. M. Piris, A. Nazarian, R. M. Maheswaran, S. Settleman, J. Wargo, J. A. Flaherty, K. T. Haber, D. A. Engelman, J. A. TI Real-time assessment of TORC1 suppression following RAF inhibitor treatment can predict responsiveness in BRAF-mutant melanoma patients SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Corcoran, R. B.; Rothenberg, S. M.; Piris, A.; Nazarian, R. M.; Maheswaran, S.; Wargo, J. A.; Flaherty, K. T.; Haber, D. A.; Engelman, J. A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Settleman, J.] Genentech Inc, Discovery Oncol, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3712 BP S859 EP S859 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605321 ER PT J AU Crnjevic, TB Chavarri-Guerra, Y Higgins, MJ Liedke, PER Symecko, H Finkelstein, D St Louis, J Vrbanec, D Goss, PE AF Crnjevic, T. Badovinac Chavarri-Guerra, Y. Higgins, M. J. Liedke, P. E. R. Symecko, H. Finkelstein, D. St Louis, J. Vrbanec, D. Goss, P. E. TI Obstacles to delivering optimal care for early breast cancer in Croatia SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Crnjevic, T. Badovinac; Vrbanec, D.] Univ Hosp Zagreb, Zagreb, Croatia. [Chavarri-Guerra, Y.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Higgins, M. J.; St Louis, J.; Goss, P. E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Liedke, P. E. R.] Hosp Clin, Clin Oncol, Affiliat Serv Oncol, Porto Alegre, RS, Brazil. [Symecko, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Finkelstein, D.] Massachusetts Gen Hosp, Canc Ctr Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 1510 BP S330 EP S330 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843602216 ER PT J AU De Bono, J Fizazi, K Shore, N Taplin, M De Wit, R Stenzl, A Hirmand, M Franks, B Scher, H AF De Bono, J. Fizazi, K. Shore, N. Taplin, M. De Wit, R. Stenzl, A. Hirmand, M. Franks, B. Scher, H. TI Assessing the impact of prior treatments on the efficacy of enzalutamide (ENZ): A subanalysis of the phase 3 AFFIRM trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [De Bono, J.] Inst Canc Res, Drug Dev Unit, London SW3 6JB, England. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Shore, N.] Carolina Urol Res Ctr, Grand Strand Urol, Myrtle Beach, SC USA. [Taplin, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [De Wit, R.] Erasmus Univ, Med Ctr, Dept Med Oncol, Rotterdam, Netherlands. [Stenzl, A.] Univ Clin Tubingen, Dept Urol, Tubingen, Germany. [Hirmand, M.] Medivation Inc, Clin Dev, San Francisco, CA USA. [Franks, B.] Astellas, Sci & Med Affairs, Northbrook, IL USA. [Scher, H.] Mem Sloan Kettering Canc Ctr, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, Genitourinary Oncol Serv, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2862 BP S683 EP S683 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604224 ER PT J AU Demetri, G Smeets, JMW Casali, PG Reichardt, P Kang, YK Joensuu, H Rutkowski, P Blay, JY Kuss, I Trnkova, ZJ AF Demetri, G. Smeets, J. M. W. Casali, P. G. Reichardt, P. Kang, Y. K. Joensuu, H. Rutkowski, P. Blay, J. Y. Kuss, I. Trnkova, Z. Jirakova TI Exposure-efficacy analysis of regorafenib (REG) and its metabolites M-2 and M-5 in the phase III GRID study in patients (pts) with metastatic gastrointestinal stromal tumor (GIST) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Demetri, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smeets, J. M. W.] LAP&P Consultants BV, PK PD, Leiden, Netherlands. [Casali, P. G.] Ist Nazl Tumori, Adult Mesenchymal Tumour Med Oncol Unit, I-20133 Milan, Italy. [Reichardt, P.] HELIOS Klinikum Berlin Buch, Interdisciplinary Oncol Sarcoma Ctr Berlin Brande, Berlin, Germany. [Kang, Y. K.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Joensuu, H.] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, P.] Inst Oncol, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Blay, J. Y.] Ctr Leon Berard, Dept Medecine, French Sarcoma Grp, F-69373 Lyon, France. [Kuss, I.] Bayer Pharma AG, Global Clin Dev Therapeut Area Oncol Ophthalmol &, Berlin, Germany. [Trnkova, Z. Jirakova] Bayer Pharma AG, GDD Clin Sci Clin Pharmacol Oncol, Berlin, Germany. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3831 BP S886 EP S886 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605400 ER PT J AU Figlin, RA Hutson, TE Tomczak, P Michaelson, MD Bjarnason, GA Lin, X Lowenthal, SP Korytowsky, B Matczak, E Oudard, S AF Figlin, R. A. Hutson, T. E. Tomczak, P. Michaelson, M. D. Bjarnason, G. A. Lin, X. Lowenthal, S. Pitman Korytowsky, B. Matczak, E. Oudard, S. TI Characterizing prior nephrectomy patients with metastatic renal cell carcinoma (mRCC) treated with first-line sunitinib versus interferon-alfa SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Figlin, R. A.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Hutson, T. E.] Baylor Sammons Canc Ctr Texas Oncol, GU Oncol Program, Dallas, TX USA. [Tomczak, P.] Uniwersytet Med, Klin Onkol, Poznan, Poland. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bjarnason, G. A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Lin, X.] Pfizer Oncol, Biostat, La Jolla, CA USA. [Lowenthal, S. Pitman] Pfizer Oncol, Asia Pacific Canada Med Oncol, New York, NY USA. [Korytowsky, B.] Pfizer Global Pharmaceut, Oncol Hlth Econ Outcomes Res, New York, NY USA. [Matczak, E.] Pfizer Oncol, Med Oncol, New York, NY USA. [Oudard, S.] Univ Paris 05, Hop Europeen Georges Pompidou, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2708 BP S644 EP S645 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843604111 ER PT J AU Finkelstein, DM AF Finkelstein, D. M. TI Correcting for partial crossover to the experimental drug in a clinical trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Finkelstein, D. M.] Harvard Univ, Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 34 BP S10 EP S10 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843600028 ER PT J AU Flaherty, K AF Flaherty, K. TI Resistance mechanisms to BRAF targeted agents SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 292 BP S67 EP S67 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843600244 ER PT J AU Flaherty, KT Lee, SJ Dummer, R Hauschild, A Hennig, M Long, GV Lorigan, P Robert, C Schadendorf, D AF Flaherty, K. T. Lee, S. J. Dummer, R. Hauschild, A. Hennig, M. Long, G. V. Lorigan, P. Robert, C. Schadendorf, D. TI A meta-analysis of randomized, controlled trials in metastatic melanoma establishes progression-free survival as a surrogate for overall survival SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Flaherty, K. T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Lee, S. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dummer, R.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Hauschild, A.] Univ Kiel, Dept Dermatol, Kiel, Germany. [Hennig, M.] GlaxoSmithkline, Biostat & Epidemiol, Munich, Germany. [Long, G. V.] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia. [Long, G. V.] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. [Lorigan, P.] Christies Hosp, Sch Oncol, Manchester, Lancs, England. [Robert, C.] Inst Gustave Roussy, Dept Dermatol, Villejuif, France. [Schadendorf, D.] Univ Hosp Essen, Dept Dermatol, Essen, Germany. RI Lorigan, Paul/J-6898-2015 OI Lorigan, Paul/0000-0002-8875-2164 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3702 BP S856 EP S856 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605311 ER PT J AU Flynn, M Shapiro, G LoRusso, P Kristeleit, R Patel, M Infante, J Giordano, H Borrow, J Jaw-Tsai, S Burris, H AF Flynn, M. Shapiro, G. LoRusso, P. Kristeleit, R. Patel, M. Infante, J. Giordano, H. Borrow, J. Jaw-Tsai, S. Burris, H., III TI A phase I dose-escalation and pk study of continuous oral rucaparib in patients with advanced solid tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Flynn, M.; Patel, M.] Univ Coll London Canc Inst, London, England. [Shapiro, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA. [Patel, M.] Florida Canc Specialists Sarah Cannon Res Inst, Sarasota, FL USA. [Infante, J.; Burris, H., III] Drug Dev Program, Sarah Cannon Res Inst, Nashville, TN USA. [Giordano, H.; Borrow, J.; Jaw-Tsai, S.] Clovis Oncol Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 881 BP S185 EP S185 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843601152 ER PT J AU Garmey, E Conley, S Keefe, S Kerberl, R Krasner, C Lazarus, D Peters, C Pham, E Wicha, M Eliasof, S AF Garmey, E. Conley, S. Keefe, S. Kerberl, R. Krasner, C. Lazarus, D. Peters, C. Pham, E. Wicha, M. Eliasof, S. TI A translational research program to evaluate the synergistic activity of CRLX101, a nanopharmaceutical in phase 2 clinical trials, with antiangiogenic therapies mediated through HIF-1 alpha inhibition SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Garmey, E.] Cerulean Pharma, Med Affairs, Cambridge, MA USA. [Conley, S.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Keefe, S.] Univ Penn, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Kerberl, R.] Sunnybrook Hlth Sci Ctr, Dept Med Biophys, Toronto, ON M4N 3M5, Canada. [Krasner, C.] Massachusetts Gen Hosp, Dept Med Hematol Oncol, Boston, MA 02114 USA. [Lazarus, D.; Peters, C.; Eliasof, S.] Cerulean Pharma, Res, Cambridge, MA USA. [Pham, E.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Wicha, M.] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 674 BP S147 EP S147 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843601029 ER PT J AU Grunwald, V Lin, X Kalanovic, D Mckay, R Perkins, J Simantov, R Choueiri, T AF Gruenwald, V. Lin, X. Kalanovic, D. McKay, R. Perkins, J. Simantov, R. Choueiri, T. TI Tumor response is an independent prognostic factor in patients (pts) treated for metastatic renal cell carcinoma (mRCC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Gruenwald, V.] Hannover Med Sch, Hannover, Germany. [Lin, X.] Pfizer Oncol, Stat, San Diego, CA USA. [Kalanovic, D.] Pfizer Pharma GmbH, Med Oncol, Berlin, Germany. [McKay, R.; Choueiri, T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perkins, J.; Simantov, R.] Pfizer Inc, Oncol Med Affairs, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2702 BP S642 EP S642 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604105 ER PT J AU Han, K Ren, M Wick, W Jin, J Abrey, L Das, A Reardon, D AF Han, K. Ren, M. Wick, W. Jin, J. Abrey, L. Das, A. Reardon, D. TI Progression-free survival as a surrogate endpoint for hazard ratio and median overall survival in glioblastoma: A literature-based meta-analysis from 91 trials SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Han, K.; Ren, M.; Jin, J.; Das, A.] Genentech Inc, Clin Pharmacol, San Francisco, CA 94080 USA. [Wick, W.] Univ Med Ctr, Dept Neurooncol, Heidelberg, Germany. [Abrey, L.] F Hoffmann La Roche Ltd, Oncol Dev, Basel, Switzerland. [Reardon, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RI Han, Kelong/J-5233-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3303 BP S775 EP S776 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843605057 ER PT J AU Hodi, F AF Hodi, F. TI Resistance to combination therapies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Hodi, F.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 294 BP S67 EP S67 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843600246 ER PT J AU Hodi, FS Topalian, SL Brahmer, JR McDermott, DF Smith, DC Gettinger, S Taube, JM Pardoll, DM Wigginton, JM Sznol, M AF Hodi, F. S. Topalian, S. L. Brahmer, J. R. McDermott, D. F. Smith, D. C. Gettinger, S. Taube, J. M. Pardoll, D. M. Wigginton, J. M. Sznol, M. TI Survival and long-term safety in patients (pts) with advanced solid tumors receiving nivolumab (anti-PD-1; BMS-936558; ONO-4538) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Hodi, F. S.] Dana Farber Canc Inst, Melanoma Ctr, Boston, MA 02115 USA. [Topalian, S. L.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Surg, Baltimore, MD USA. [Brahmer, J. R.; Pardoll, D. M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, Boston, MA 02215 USA. [Smith, D. C.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Gettinger, S.] Yale Canc Ctr, Dept Oncol, New Haven, CT USA. [Taube, J. M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Dermatol, Baltimore, MD USA. [Taube, J. M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Pathol, Baltimore, MD USA. [Wigginton, J. M.] Bristol Myers Squibb Co, Dept Immunooncol Early Clin Res, Princeton, NJ USA. [Sznol, M.] Yale Canc Ctr, Dept Internal Med Med Oncol, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 880 BP S185 EP S185 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843601151 ER PT J AU Hodi, FS Powles, T Cassier, P Kowanetz, M Herbst, RS Soria, JC Mokatrin, A Stroh, M Chen, DS Tabernero, J AF Hodi, F. S. Powles, T. Cassier, P. Kowanetz, M. Herbst, R. S. Soria, J. C. Mokatrin, A. Stroh, M. Chen, D. S. Tabernero, J. TI MPDL3280A (anti-PDL1): Clinical activity, safety and biomarkers of an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Hodi, F. S.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Powles, T.] Barts Canc Inst QMUL Barts Hlth NHS Trust, London, England. [Cassier, P.] Ctr Leon Berard, F-69373 Lyon, France. [Kowanetz, M.] Genentech Inc, Oncol Biomarker Dev, San Francisco, CA 94080 USA. [Herbst, R. S.] Yale Univ, Sch Med, New Haven, CT USA. [Soria, J. C.] Inst Gustave Roussy, Villejuif, France. [Mokatrin, A.] Genentech Inc, Biostat, San Francisco, CA 94080 USA. [Stroh, M.] Genentech Inc, Pharmacokinet, San Francisco, CA 94080 USA. [Chen, D. S.] Genentech Inc, Oncol Dev, San Francisco, CA 94080 USA. [Tabernero, J.] Vall dHebron Univ Hosp, Barcelona, Spain. NR 0 TC 2 Z9 2 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 879 BP S184 EP S184 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843601150 ER PT J AU Juric, D Infante, JR Krop, IE Kurkjian, C Patel, MR Graham, RA Wilson, TR Hsu, JY Baselga, J Von Hoff, DD AF Juric, D. Infante, J. R. Krop, I. E. Kurkjian, C. Patel, M. R. Graham, R. A. Wilson, T. R. Hsu, J. Y. Baselga, J. Von Hoff, D. D. TI Evaluation of tolerability and anti-tumor activity of GDC-0032, a PI3K inhibitor with enhanced activity against PIK3CA mutant tumors, administered-to patients with advanced solid tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Juric, D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Infante, J. R.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Krop, I. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kurkjian, C.] Univ Oklahoma, Norman, OK 73019 USA. [Patel, M. R.] Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA. [Graham, R. A.; Wilson, T. R.; Hsu, J. Y.] Genentech Inc, San Francisco, CA 94080 USA. [Baselga, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Von Hoff, D. D.] Virginia G Piper Canc Ctr TGen, Scottsdale, AZ USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 822 BP S168 EP S168 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843601095 ER PT J AU Kibel, A Drake, C Yu, E Adams, G Karsh, L Elfiky, A Vogelzang, N Shore, N Tyler, R Antonarakis, E AF Kibel, A. Drake, C. Yu, E. Adams, G. Karsh, L. Elfiky, A. Vogelzang, N. Shore, N. Tyler, R. Antonarakis, E. TI Metastatic disease detection is an important cause of screen failures in a phase II trial evaluating the optimal sequence of androgen deprivation therapy and sipuleucel-T in hormone-naive patients with biochemically-recurrent prostate cancer (BRPC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Kibel, A.; Elfiky, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Drake, C.] Johns Hopkins, Med Oncol Immunol & Urol, Baltimore, MD USA. [Yu, E.] Univ Washington, Seattle, WA 98195 USA. [Adams, G.] Urol Ctr Alabama, Birmingham, AL USA. [Karsh, L.] Urol Ctr Colorado, Dept Clin Res, Denver, CO USA. [Vogelzang, N.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Tyler, R.] Dendreon Corp, Med Affairs, Seattle, WA USA. [Antonarakis, E.] Johns Hopkins Med, Oncol, Baltimore, MD USA. RI Antonarakis, Emmanuel/E-4550-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2903 BP S697 EP S698 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843604265 ER PT J AU Lacouture, M Grunberg, S Keefe, D Sonis, S Ely, J Gernhardt, D Wang, T Doherty, J O'Connell, J Jatoi, A AF Lacouture, M. Grunberg, S. Keefe, D. Sonis, S. Ely, J. Gernhardt, D. Wang, T. Doherty, J. O'Connell, J. Jatoi, A. TI Impact of doxycycline (doxy) prophylaxis on dermatologic toxicity from dacomitinib (D) for NSCLC, by CTCAE and patient (pt)-reported outcomes (PRO) measures in a placebo-controlled trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Lacouture, M.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Grunberg, S.; Ely, J.] Univ Vermont, Fletcher Allen Hlth Care, Burlington, VT 05405 USA. [Keefe, D.] Univ Adelaide, Royal Adelaide Hosp, Adelaide, SA, Australia. [Sonis, S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gernhardt, D.; Wang, T.; Doherty, J.; O'Connell, J.] Pfizer Oncol, Med Oncol, Groton, CT USA. [Jatoi, A.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3466 BP S817 EP S817 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605187 ER PT J AU Mehra, R Lee, JW Egloff, AM Yang, DH Grandis, JR Burtness, BA Langer, CJ Forastiere, AA AF Mehra, R. Lee, J. W. Egloff, A. M. Yang, D. H. Grandis, J. R. Burtness, B. A. Langer, C. J. Forastiere, A. A. TI Association of XPF and HPV among squamous cell head and neck cancer tumors: Biomarker analysis of ECOG 3303 SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Mehra, R.; Yang, D. H.; Burtness, B. A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Lee, J. W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Egloff, A. M.; Grandis, J. R.] Univ Pittsburgh, Head & Neck Canc Program, Pittsburgh, PA USA. [Langer, C. J.] Univ Penn, Philadelphia, PA 19104 USA. [Forastiere, A. A.] Johns Hopkins, Med Oncol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3152 BP S744 EP S744 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604410 ER PT J AU Ribas, A Hodi, FS Callahan, M Chmielowski, B Lawrence, D Konto, C McHenry, MB Choong, N Wolchok, J AF Ribas, A. Hodi, F. S. Callahan, M. Chmielowski, B. Lawrence, D. Konto, C. McHenry, M. B. Choong, N. Wolchok, J. TI Phase I trial evaluating concurrent vemurafenib and ipilimumab in patients with advanced BRAF-mutant melanoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Ribas, A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Callahan, M.; Wolchok, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chmielowski, B.] Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA USA. [Lawrence, D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Konto, C.] Bristol Myers Squibb Co, Oncol Global Clin Res, Wallingford, CT 06492 USA. [McHenry, M. B.] Bristol Myers Squibb Co, Global Biometr Sci, Wallingford, CT 06492 USA. [Choong, N.] Roche, Prod Dev Oncol, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3736 BP S867 EP S867 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605344 ER PT J AU Rodon, J Dienstmann, R Tabernero, J AF Rodon, J. Dienstmann, R. Tabernero, J. TI Genetic analysis in advanced cancer patients: What test for which patient? Matching patient, biomarker and drug SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Rodon, J.; Tabernero, J.] Vall DHebron Univ Hosp, Barcelona, Spain. [Dienstmann, R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 316 BP S72 EP S72 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843600264 ER PT J AU Ryan, CJ Kheoh, T Molina, A Carles, J Efstathiou, E Kantoff, PW Mulders, PFA Saad, F Griffin, T Chi, KN AF Ryan, C. J. Kheoh, T. Molina, A. Carles, J. Efstathiou, E. Kantoff, P. W. Mulders, P. F. A. Saad, F. Griffin, T. Chi, K. N. TI Prognostic index for progression-free survival in metastatic castration-resistant prostate cancer patients without previous chemotherapy: An analysis of the COU-AA-302 abiraterone acetate study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Ryan, C. J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Kheoh, T.] Janssen Res & Dev, Biostat & Programming, Los Angeles, CA USA. [Molina, A.] Janssen Res & Dev, Oncol, Los Angeles, CA USA. [Carles, J.] Vall dHebron Univ Hosp, Barcelona, Spain. [Efstathiou, E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kantoff, P. W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kantoff, P. W.] Harvard Univ, Sch Med, Boston, MA USA. [Mulders, P. F. A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Saad, F.] Univ Montreal, Div Urol, Montreal, PQ, Canada. [Griffin, T.] Janssen Res & Dev, WC Clin Oncol, Los Angeles, CA USA. [Chi, K. N.] BC Canc Agcy, Oncol, Vancouver, BC, Canada. RI Mulders, Peter/H-8076-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2863 BP S683 EP S684 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843604225 ER PT J AU Smith, M Borre, M Rathenborg, P Werbrouck, P Van Poppel, H Heidenreich, A Iversen, P Baskin-Bey, E Perabo, F Phung, D Tombal, B AF Smith, M. Borre, M. Rathenborg, P. Werbrouck, P. Van Poppel, H. Heidenreich, A. Iversen, P. Baskin-Bey, E. Perabo, F. Phung, D. Tombal, B. TI Enzalutamide (ENZA) monotherapy in hormone naive prostate cancer (HNPC): Complete analysis of a phase 2 study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA USA. [Borre, M.] Aarhus Univ Hosp, Dept Urol, Skejby, Denmark. [Rathenborg, P.] Herlev Hosp, Dept Urol, DK-2730 Herlev, Denmark. [Werbrouck, P.] AZ Groeninge Kortrijk, Dept Urol, Kortrijk, Belgium. [Van Poppel, H.] UZ Leuven, Dept Urol, Louvain, Belgium. [Heidenreich, A.] Univ Klinikum RWTH Aachen, Dept Urol, North Rhine Westphalia, Germany. [Iversen, P.] Univ Copenhagen, Rigshosp, Dept Urol, DK-2100 Copenhagen, Denmark. [Phung, D.] Astellas, Global Data Sci, Leiderdorp, Netherlands. [Tombal, B.] Clin Univ St Luc, Serv Urol, B-1200 Brussels, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2852 BP S680 EP S680 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604215 ER PT J AU Smith, M AF Smith, M. TI Non-androgen receptor (AR) targeted approaches for managing castration-resistant prostate cancer (CRPC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Smith, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 393 BP S89 EP S89 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843600327 ER PT J AU Smith, MR Rathkopf, D Mulders, P Carles, J Van Poppel, H Li, J Kheoh, T Griffin, T Molina, A Ryan, C AF Smith, M. R. Rathkopf, D. Mulders, P. Carles, J. Van Poppel, H. Li, J. Kheoh, T. Griffin, T. Molina, A. Ryan, C. TI Efficacy and safety of abiraterone acetate (AA) in elderly (75 years) chemo-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Rathkopf, D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mulders, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Carles, J.] Vall dHebron Univ Hosp, Barcelona, Spain. [Van Poppel, H.] Univ Hosp KU Leuven, Louvain, Belgium. [Li, J.] Janssen Res & Dev, Biostat Oncol, Raritan, NJ USA. [Kheoh, T.] Janssen Res & Dev, Biostat & Programming, Los Angeles, CA USA. [Griffin, T.] Janssen Res & Dev, WC Clin Oncol, Los Angeles, CA USA. [Molina, A.] Janssen Res & Dev, Oncol, Los Angeles, CA USA. [Ryan, C.] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA. RI Mulders, Peter/H-8076-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2932 BP S708 EP S708 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604294 ER PT J AU Smith, MR Antonarakis, ES Ryan, CJ Berry, WR Shore, ND Liu, G Alumkal, JJ Higano, CS Maneval, EC Rathkopf, DE AF Smith, M. R. Antonarakis, E. S. Ryan, C. J. Berry, W. R. Shore, N. D. Liu, G. Alumkal, J. J. Higano, C. S. Maneval, E. Chow Rathkopf, D. E. TI ARN-509 in men with high risk non-metastatic castration-resistant prostate cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Smith, M. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Antonarakis, E. S.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Ryan, C. J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Berry, W. R.] Canc Ctr North Carolina, Raleigh, NC USA. [Shore, N. D.] Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Liu, G.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Alumkal, J. J.] OHSU Knight Canc Inst, Portland, OR USA. [Higano, C. S.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Maneval, E. Chow] Aragon Pharmaceut, Oncol Clin Dev, San Diego, CA USA. [Rathkopf, D. E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Antonarakis, Emmanuel/E-4550-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2898 BP S695 EP S695 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604260 ER PT J AU Smith, MR Fizazi, K Miller, K Egerdie, B Morote, J Tammela, TL Wong, S Ye, Z Braun, A AF Smith, M. R. Fizazi, K. Miller, K. Egerdie, B. Morote, J. Tammela, T. L. Wong, S. Ye, Z. Braun, A. TI Denosumab in men with nonmetastatic castration-resistant prostate cancer (CRPC) at high risk for bone metastases SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. [Miller, K.] Charite, Berlin, Germany. [Morote, J.] Hosp Valle De Hebron, Barcelona, Spain. [Tammela, T. L.] Tampere Univ Hosp, Tampere, Finland. [Wong, S.] Western Hosp, Footscray, Vic, Australia. [Ye, Z.; Braun, A.] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2859 BP S682 EP S682 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604222 ER PT J AU Sonpavde, G Anderson, JC Welaya, K Chen, D Mehta, A Ghatalia, P Sudarshan, S Grizzle, WE Choueiri, TK Willey, CD AF Sonpavde, G. Anderson, J. C. Welaya, K. Chen, D. Mehta, A. Ghatalia, P. Sudarshan, S. Grizzle, W. E. Choueiri, T. K. Willey, C. D. TI Comprehensive activated kinase profiling to identify novel therapeutic targets in metastatic clear cell (cc)-renal cell carcinoma (RCC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Sonpavde, G.; Anderson, J. C.; Welaya, K.; Chen, D.; Mehta, A.; Ghatalia, P.; Sudarshan, S.; Grizzle, W. E.; Willey, C. D.] UAB, Ctr Canc, Birmingham, AL USA. [Choueiri, T. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, T. K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2796 BP S674 EP S674 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604199 ER PT J AU Sonpavde, G Di Lorenzo, G Necchi, A Eigl, B Kolinsky, M Chacko, R Dorff, T Harshman, L Goyal, J Pond, G AF Sonpavde, G. Di Lorenzo, G. Necchi, A. Eigl, B. Kolinsky, M. Chacko, R. Dorff, T. Harshman, L. Goyal, J. Pond, G. TI Prognostic risk stratification of men with advanced penile squamous cell cancer (PSCC) receiving first-line systemic therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Sonpavde, G.; Goyal, J.] Univ Alabama Birmingham, Ctr Canc, Birmingham, AL USA. [Di Lorenzo, G.] Univ Naples Federico II, Genitourinary Canc Sect, Naples, Italy. [Di Lorenzo, G.] Rare Canc Ctr, Naples, Italy. [Necchi, A.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Eigl, B.] BC Canc Agcy, Vancouver, BC, Canada. [Kolinsky, M.] Univ Alberta, Edmonton, AB, Canada. [Chacko, R.] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Dorff, T.] Univ So Calif, Los Angeles, CA USA. [Harshman, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pond, G.] McMaster Univ, Hamilton, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 2715 BP S647 EP S647 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843604118 ER PT J AU Stupp, R Hegi, ME Gorlia, T Perry, JR Erridge, S Reardon, DA Markivskyy, A Wick, W Hong, YK Weller, M AF Stupp, R. Hegi, M. E. Gorlia, T. Perry, J. R. Erridge, S. Reardon, D. A. Markivskyy, A. Wick, W. Hong, Y. K. Weller, M. TI Standard chemoradiotherapy +/- cilengitide in newly diagnosed glioblastoma (GBM): Updated results and subgroup analyses of the international randomized phase III CENTRIC trial (EORTC trial #26071-22072/Canadian Brain Tumor Consortium) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2013 - 17th ECCO / 38th ESMO / 32nd ESTRO CY SEP 27-OCT 01, 2013 CL Amsterdam, NETHERLANDS SP European Conf Clin Oncol, European Soc Therapeut Radiol & Oncol, European Soc Med Oncol, European Soc Surg Oncol, European Assoc Canc Res, European Oncol Nursing Soc, European Soc Paediat Oncol C1 [Stupp, R.; Hegi, M. E.] CHU Vaudois, Dept Clin Neurosci, CH-1011 Lausanne, Switzerland. [Gorlia, T.] EORTC, Ctr Data, Brussels, Belgium. [Perry, J. R.] Sunnybrook Hlth Sci Ctr, Div Neurol, Toronto, ON M4N 3M5, Canada. [Erridge, S.] Univ Edinburgh, Edinburgh Canc Ctr, Edinburgh, Midlothian, Scotland. [Reardon, D. A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Markivskyy, A.] Merck KGaA, Global Clin Dev Unit Oncol, Darmstadt, Germany. [Wick, W.] Univ Klin Heidelberg, Neurol Klin, Heidelberg, Germany. [Wick, W.] Natl Tumorzentrum, Heidelberg, Germany. [Hong, Y. K.] Catholic Univ Korea, Seoul St Marys Hosp, Seoul, South Korea. [Weller, M.] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 SU 2 MA 3302 BP S775 EP S775 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843605056 ER EF