FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Temel, J Bondarde, S Jain, M Allen, S Mann, W AF Temel, J. Bondarde, S. Jain, M. Allen, S. Mann, W. TI Efficacy and safety of anamorelin HCl in NSCLC patients: Results from a randomized, double-blind, placebo-controlled, multicenter phase II 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 [Temel, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bondarde, S.] Shatabdi Super Specialty Hosp, Nasik, Maharashtra, India. [Jain, M.] Xylem Clin Res Pvt Ltd, Ruby Hall Clin, Pune, Maharashtra, India. [Allen, S.; Mann, W.] Helsinn Therapeut US Inc, Res & Dev, Bridgewater, MA USA. NR 0 TC 1 Z9 1 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 1308 BP S269 EP S270 PG 2 WC Oncology SC Oncology GA 250HY UT WOS:000326843602015 ER PT J AU Verbeek, FPR Troyan, SL Mieog, JSD Liefers, GJ Van De Velde, CJH Vahrmeijer, AL Frangioni, JV AF Verbeek, F. P. R. Troyan, S. L. Mieog, J. S. D. Liefers, G. J. Van de Velde, C. J. H. Vahrmeijer, A. L. Frangioni, J. V. TI Near-infrared fluorescence sentinel lymph node mapping in breast cancer: A multicenter experience 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 [Verbeek, F. P. R.; Mieog, J. S. D.; Liefers, G. J.; Van de Velde, C. J. H.; Vahrmeijer, A. L.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Troyan, S. L.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Frangioni, J. V.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 1250 BP S260 EP S260 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843601397 ER PT J AU Yang, JCH Sequist, L O'Byrne, K Schuler, M Mok, T Geater, S Massey, D O'Brien, D Zazulina, V Wu, YL AF Yang, J. Chih-Hsin Sequist, L. O'Byrne, K. Schuler, M. Mok, T. Geater, S. Massey, D. O'Brien, D. Zazulina, V. Wu, Y. L. TI Epidermal growth factor receptor (EGFR)-mediated adverse events (AEs) in patients (pts) with EGFR mutation positive (EGFR M plus ) non-small cell lung cancer treated with afatinib 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 [Yang, J. Chih-Hsin] Natl Taiwan Univ Hosp, Grad Inst Oncol, Taipei, Taiwan. [Yang, J. Chih-Hsin] Canc Res Ctr, Taipei, Taiwan. [Sequist, L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [O'Byrne, K.] St James Hosp, Dublin 8, Ireland. [Schuler, M.] Univ Duisburg Essen, West German Canc Ctr, Essen, Germany. [Mok, T.] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Geater, S.] Prince Songkla Univ, Hat Yai, Thailand. [Massey, D.; Zazulina, V.] Boehringer Ingelheim Ltd, Bracknell, Berks, England. [O'Brien, D.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Wu, Y. L.] Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China. NR 0 TC 4 Z9 4 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 895 BP S190 EP S190 PG 1 WC Oncology SC Oncology GA 250HY UT WOS:000326843601166 ER PT J AU Hastie, PA Calderon, A Rolim, RJ Guarino, AJ AF Hastie, Peter A. Calderon, Antonio Rolim, Ramiro J. Guarino, Anthony J. TI The Development of Skill and Knowledge During a Sport Education Season of Track and Field Athletics SO RESEARCH QUARTERLY FOR EXERCISE AND SPORT LA English DT Article DE accountability; instructional models; Portugal; secondary school physical education ID PHYSICAL-EDUCATION AB Purpose: The purpose of this study was to examine the relative effectiveness of 2 forms of physical education instruction on students' skill and technical performance, as well as content knowledge in 3 track and field events. Method: Students from 6 classes in 3 Portuguese schools completed 900-min units conducted under the auspices of sport education or a more traditional teacher-directed format. Classes were randomly assigned to these conditions within each school. Results: Although both groups improved significantly from pretest to posttest, the sport education classes outperformed the traditional classes in both technique and skill execution. Only the sport education group made significant improvements in content knowledge. When the students in the traditional group were tested at the point in time where they would usually complete a unit of physical education (450 min), there were no significant improvements in any of the study's variables. Conclusion: The explanation given for the superior performance outcomes of the sport education classes lies in the nature of formal competition and team affiliation, which are cornerstones of this pedagogical model. That is, students take their learning experiences more seriously than in traditional and often inauthentic classes. In terms of content knowledge, the fact that sport education has a level of content-embedded accountability that holds students accountable for their officiating duties is postulated as a significant contributor to their increased understanding of rules and protocols of athletic events. C1 [Hastie, Peter A.] Auburn Univ, Auburn, AL 36849 USA. [Calderon, Antonio] Catholic Univ San Antonio, San Antonio, TX USA. [Rolim, Ramiro J.] Univ Porto, P-4100 Oporto, Portugal. [Guarino, Anthony J.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Hastie, PA (reprint author), Auburn Univ, Dept Hlth & Human Performance, 2050 Mem Coliseum, Auburn, AL 36849 USA. EM hastipe@auburn.edu RI Calderon, Antonio/E-5328-2010 OI Calderon, Antonio/0000-0003-1389-9898 FU Seneca Foundation-Agency for Science and Technology in the Murcia Region within the framework of II PCTRM [11682/IV2/09] FX This work is the result of the funding 11682/IV2/09 granted by the Seneca Foundation-Agency for Science and Technology in the Murcia Region within the framework of II PCTRM 2007-2010. NR 34 TC 17 Z9 19 U1 5 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0270-1367 EI 2168-3824 J9 RES Q EXERCISE SPORT JI Res. Q. Exerc. Sport PD SEP 1 PY 2013 VL 84 IS 3 BP 336 EP 344 DI 10.1080/02701367.2013.812001 PG 9 WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology; Sport Sciences SC Social Sciences - Other Topics; Psychology; Sport Sciences GA 218KG UT WOS:000324430700008 PM 24261013 ER PT J AU King, B Geary, J Sturtevant, OJ Ritz, J Kao, G AF King, B. Geary, J. Sturtevant, O. J. Ritz, J. Kao, G. TI Comparative Predictive Value of Peripheral CD34 and Novel Parameters in Stem Cell Mobilization SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 12-15, 2013 CL Denver, CO SP AABB C1 [King, B.; Sturtevant, O. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Geary, J.; Ritz, J.; Kao, G.] Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA. EM bking3@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2013 VL 53 SU 2 SI SI BP 65A EP 65A PG 1 WC Hematology SC Hematology GA 218CA UT WOS:000324409000126 ER PT J AU Stasko, KD Hansen, HM AF Stasko, K. D. Hansen, H. M. TI Bridging the Gap: Providing a Web-Based Forum for Education and Communication in a Challenging Workplace Environment SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 12-15, 2013 CL Denver, CO SP AABB C1 [Stasko, K. D.; Hansen, H. M.] Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA. EM karl_stasko@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2013 VL 53 SU 2 SI SI BP 248A EP 248A PG 1 WC Hematology SC Hematology GA 218CA UT WOS:000324409000583 ER PT J AU Stapleton, CJ Ogilvy, CS AF Stapleton, Christopher J. Ogilvy, Christopher S. TI Treatment of Intracranial Aneurysms with the Pipeline Embolization Device from a U.S. Multicenter Experience SO WORLD NEUROSURGERY LA English DT News Item ID RECONSTRUCTION C1 [Stapleton, Christopher J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stapleton, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD SEP-OCT PY 2013 VL 80 IS 3-4 BP 231 EP 233 DI 10.1016/j.wneu.2013.07.008 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 247WM UT WOS:000326653900025 PM 23871814 ER PT J AU Peruzzi, P Chiocca, EA AF Peruzzi, Pierpaolo Chiocca, E. Antonio TI Understanding Glioma Invasion: A Necessity for Effective Therapy SO WORLD NEUROSURGERY LA English DT Editorial Material DE Glioma; Invasion; Matrix metalloproteinase-9; Migration; NF-E2 related factor 2 ID TUMOR; GLIOBLASTOMA; MIGRATION; CELLS; IRRADIATION; INVOLVEMENT C1 [Peruzzi, Pierpaolo] Ohio State Univ, Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA. [Peruzzi, Pierpaolo] James Canc Hosp, Columbus, OH USA. [Chiocca, E. Antonio] Harvard Univ, Sch Med, Inst Neurosci, Dept Neurosurg,Brigham & Womens Faulker Hosp, Boston, MA USA. [Chiocca, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM eachiocca@partners.org NR 20 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD SEP-OCT PY 2013 VL 80 IS 3-4 BP 281 EP 283 DI 10.1016/j.wneu.2011.10.003 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 247WM UT WOS:000326653900039 PM 22120237 ER PT J AU Gephart, MGH Hansasuta, A Balise, RR Choi, C Sakamoto, GT Venteicher, AS Soltys, SG Gibbs, IC Harsh, GR Adler, JR Chang, SD AF Gephart, Melanie G. Hayden Hansasuta, Ake Balise, Raymond R. Choi, Clara Sakamoto, Gordon T. Venteicher, Andrew S. Soltys, Scott G. Gibbs, Iris C. Harsh, Griffith R. Adler, John R. Chang, Steven D. TI Cochlea Radiation Dose Correlates with Hearing Loss After Stereotactic Radiosurgery of Vestibular Schwannoma SO WORLD NEUROSURGERY LA English DT Article DE Cochlea; Hearing preservation; Radiation; Stereotactic radiosurgery; Vestibular schwannoma ID GAMMA-KNIFE RADIOSURGERY; ACOUSTIC NEUROMA RADIOSURGERY; 13 GY; PRESERVATION; IRRADIATION; EXPERIENCE; SURGERY AB OBJECTIVE: For multisession radiosurgery, no published data relate the volume and dose of cochlear irradiation to quantified risk of hearing loss. We conducted a retrospective, dosimetric study to evaluate the relationship between hearing loss after stereotactic radiosurgery (SRS) and the dose-volume of irradiated cochlea. METHODS: Cochlear dose data were retrospectively collected on consecutive patients who underwent SRS (18 Gy in 3 sessions) for vestibular schwanoma between 1999 and 2005 at Stanford University Hospital. Inclusion criteria included Gardner-Robertson (GR) grade I or II hearing prior to radiosurgical treatment, complete audiograms, and magnetic resonance imaging (MRI) follow-up. A cochlea dose-volume histogram was generated for each of the 94 patients who qualified for this study. RESULTS: GR grade I-II hearing posttreatment was maintained in 74% of patients (70/94). Median time to last follow-up audiogram was 2.4 years (range 0.4-8.9) and to last MRI was 3.6 years (range 0.5-9.4). Each higher level of cochlear irradiation was associated with increased risk of hearing loss. Larger cochlear volume was associated with lower risk of hearing loss. Controlling for differences in cochlear volume among subjects, each additional mm(3) of cochlea receiving 10 to 16 Gy (single session equivalent doses of 6.6-10.1 Gy(3)) significantly increased the odds of hearing loss by approximately 5%. CONCLUSIONS: Larger cochlear volume is associated with lower risk of hearing loss following trisession SRS for vestibular schwannoma. Controlling for this phenomenon, higher radiation dose and larger irradiated cochlear volume are significantly associated with higher risk of hearing loss. This study confirms and quantifies the risk of hearing loss following trisession SRS for vestibular schwannoma. C1 [Gephart, Melanie G. Hayden; Choi, Clara; Harsh, Griffith R.; Adler, John R.; Chang, Steven D.] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA. [Balise, Raymond R.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Soltys, Scott G.; Gibbs, Iris C.] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. [Hansasuta, Ake] Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Neurosurg,Dept Surg, Bangkok 10400, Thailand. [Sakamoto, Gordon T.] Palo Alto Med Fdn, Palo Alto, CA USA. [Venteicher, Andrew S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Chang, SD (reprint author), Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA. EM sdchang@stanford.edu FU California Institute of Regenerative Medicine FX Dr. John Adler is Vice President of Varian Medical, Inc., Dr. Iris Gibbs is a member of the Clinical Advisory Board and the Speakers' Bureau of Accuray, Inc., manufacturer of the CyberKnife radiosurgical system. This work is in part supported by gifts from Robert C. and Jeannette Powell, Alan Wong and Sylvia Tang, and Paula and William Zappettini to Steven D. Chang, MD. M. G. Hayden Gephart is supported by a postdoctoral fellowship from the California Institute of Regenerative Medicine. NR 20 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD SEP-OCT PY 2013 VL 80 IS 3-4 BP 359 EP 363 DI 10.1016/j.wneu.2012.04.001 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 247WM UT WOS:000326653900061 ER PT J AU Patel, SR Aronson, JP Sheth, SA Eskandar, EN AF Patel, Shaun R. Aronson, Joshua P. Sheth, Sameer A. Eskandar, Emad N. TI Lesion Procedures in Psychiatric Neurosurgery SO WORLD NEUROSURGERY LA English DT Article DE Major depression; Neurosurgery; Obsessive-compulsive disorder; Stereotactic; Surgery ID OBSESSIVE-COMPULSIVE DISORDER; STEREOTACTIC SUBCAUDATE TRACTOTOMY; TERM-FOLLOW-UP; NUCLEUS-ACCUMBENS; LIMBIC LEUKOTOMY; DRUG-ADDICTION; STRUCTURAL ABNORMALITIES; PSYCHOLOGICAL DEPENDENCE; ANTERIOR CINGULOTOMY; PSYCHOSURGERY AB OBJECTIVE: Lesion procedures for psychiatric indications have a history that spans more than a century. This review provides a brief history of psychiatric surgery and addresses the most recent literature on lesion surgery for the treatment of anxiety and mood disorders. METHODS: Relevant data described in publications from the early 1900s through the modern era regarding lesion procedures for psychiatric indications, both historical and current use, are reported. RESULTS: The early procedures of Burkhardt, Moniz, and Freeman are reviewed, followed by descriptions of the more refined techniques of Leksell, Knight, Foltz, White, and Kelly. The application of lesion procedures to obsessive-compulsive disorder, mood disorders, and addiction are discussed. CONCLUSIONS: Lesioning procedures have informed modern deep brain stimulation targets. Recent lesioning studies demonstrate the efficacy and durability of these procedures in severely disabled patients. Judicious application of these techniques should continue for appropriately selected patients with severe, refractory psychiatric disorders. C1 [Patel, Shaun R.; Aronson, Joshua P.; Sheth, Sameer A.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM eeskandar@partners.org NR 71 TC 4 Z9 4 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD SEP-OCT PY 2013 VL 80 IS 3-4 AR UNSP S31.E9 DI 10.1016/j.wneu.2012.11.038 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 247WM UT WOS:000326653900017 PM 23159652 ER PT J AU Privette, ED Werth, VP AF Privette, Emily D. Werth, Victoria P. TI Update on pathogenesis and treatment of CLE SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE Cutaneous Lupus Disease Area and Severity Index; Cutaneous Lupus Erythematous; hydroxychloroquine; interferon ID CUTANEOUS LUPUS-ERYTHEMATOSUS; AICARDI-GOUTIERES SYNDROME; BLOOD MONONUCLEAR-CELLS; DISEASE-ACTIVITY; SEVERITY INDEX; RENAL-DISEASE; EFFICACY; THERAPY; SMOKING; HYDROXYCHLOROQUINE AB Purpose of review Cutaneous Lupus Erythematous (CLE) is an autoimmune disease in which patients may present with isolated skin findings or have CLE associated with underlying systemic disease. The most significant recent studies on its pathogenesis and therapeutic management are reviewed here. Recent findings Patients with subacute and Discoid Lupus Erythematous had elevated Interferon score, about a third of all cases of SCLE could be attributed to previous drug exposure, and smoking may be more closely associated with CLE than Systemic Lupus Erythematous (SLE). An underlying genetic defect in some subsets of CLE patients may also be shared with SLE. Efficacy of antimalarial therapy is enhanced by increasing treatment duration or maintaining higher blood drug concentrations. Combination antimalarials that include quinacrine, thalidomide analogs, and Mycophenalate Mofetil may also be effective in refractory CLE. Summary The pathogenesis of CLE remains unclear, and is likely multifactorial. Identified associations with subsets of CLE suggest future research questions in CLE pathogenesis. Subsets of CLE associated with interface dermatitis may share an underlying genetic defect in interferon signaling with SLE. The Cutaneous Lupus Disease Area and Severity Index is a valuable and widely used tool allowing standardized assessment and reporting of cutaneous disease activity and damage. More evidence is available to guide treatment of refractory CLE, but larger studies are needed. Video abstract http://links.lww.com/COR/A4. C1 [Privette, Emily D.; Werth, Victoria P.] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Privette, Emily D.; Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development); National Institutes of Health [NIH K24-AR 02207] FX This material is based upon work supported by a Merit Review Grant from the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) and by the National Institutes of Health (NIH K24-AR 02207) to V.P.W. NR 43 TC 7 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 EI 1531-6963 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD SEP PY 2013 VL 25 IS 5 BP 584 EP 590 DI 10.1097/BOR.0b013e32836437ba PG 7 WC Rheumatology SC Rheumatology GA 248KD UT WOS:000326697400004 PM 23872903 ER PT J AU Tirumani, SH Jagannathan, JP Shinagare, AB Kim, KW Krajewski, KM Ramaiya, NH AF Tirumani, Sree Harsha Jagannathan, Jyothi P. Shinagare, Atul B. Kim, Kyung Won Krajewski, Katherine M. Ramaiya, Nikhil H. TI Acute pancreatitis associated with molecular targeted therapies: A retrospective review of the clinico-radiological features, management and outcome SO PANCREATOLOGY LA English DT Review DE Molecular targeted therapy; Acute pancreatitis; MDCT; Cancer ID REFRACTORY SOLID TUMORS; JAPANESE PATIENTS; PHASE-I; SORAFENIB; INHIBITOR; CARCINOMA; KINASE AB Purpose: To study the presentation, radiological features, management and outcome of acute pancreatitis detected on imaging in patients receiving molecular targeted therapy (MTT). Materials and methods: In this IRE-approved, HIPAA-compliant retrospective study, search of the radiology database from January 2005 through September 2012 revealed 91 cancer patients with radiologic evidence of acute pancreatitis. Of these, 15 patients receiving MU (7 women, 8 men; mean age 59 years, range 25-84 years) and fulfilling the criteria of acute pancreatitis without any confounding factors were included. Imaging at initial diagnosis of pancreatitis and subsequently were reviewed by three radiologists in consensus; clinical presentation, management, and outcome were documented from the medical record. Results: Eleven patients had focal and four had diffuse pancreatitis. The tail of the pancreas (n = 6) was the most common site of focal pancreatitis. Of the 14/15 patients who underwent CT, modified CT severity index was 2 in 12 patients and 4 in 2 patients. One patient (1/15) who underwent only FDG-PET/CT showed focal pancreatitis. None of the patients had pancreatic necrosis or peripancreatic collections. Findings resolved in all the patients after discontinuation of MTT, except in one patient who died of progressive disease. No radiological or surgical interventions were required in any of the patients. Findings recurred in 4/9 patients (44%) in whom MTT was restarted. Conclusion: MTT-associated pancreatitis is usually mild, focal, and managed conservatively with discontinuation of MTT. The imaging findings are subtle and in our study, pancreatitis recurred in 44% of patients after restarting MTT. Copyright (C) 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. C1 [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Shinagare, Atul B.; Kim, Kyung Won; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Shinagare, Atul B.; Kim, Kyung Won; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org; jjagannathan@partners.org; ashinagare@partners.org; medimash@gmail.com; kmkrajewski@partners.org; nramaiya@partners.org NR 15 TC 7 Z9 7 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 EI 1424-3911 J9 PANCREATOLOGY JI Pancreatology PD SEP-OCT PY 2013 VL 13 IS 5 BP 461 EP 467 DI 10.1016/j.pan.2013.08.001 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 245SG UT WOS:000326483500001 PM 24075509 ER PT J AU Brown, DE Libby, SJ Moreland, SM McCoy, MW Brabb, T Stepanek, A Fang, FC Detweiler, CS AF Brown, D. E. Libby, S. J. Moreland, S. M. McCoy, M. W. Brabb, T. Stepanek, A. Fang, F. C. Detweiler, C. S. TI Salmonella enterica Causes More Severe Inflammatory Disease in C57/BL6 Nramp 1(G169) Mice Than Sv129S6 Mice SO VETERINARY PATHOLOGY LA English DT Article DE anemia; dendritic cells; inflammation; macrophages; mouse; Nramp1; Salmonella enterica; typhoid fever ID MOUSE STRAIN DIFFERENCES; MURINE TYPHOID-FEVER; SEROVAR TYPHIMURIUM; IRON-DEFICIENCY; GENETIC-ANALYSIS; SV. TYPHIMURIUM; EXPRESSION; INFECTION; MACROPHAGES; RESISTANCE AB Salmonella enterica serovar Typhimurium (S. Typhimurium) causes systemic inflammatory disease in mice by colonizing cells of the mononuclear leukocyte lineage. Mouse strains resistant to S. Typhimurium, including Sv129S6, have an intact Nramp1 (Slc11a1) allele and survive acute infection, whereas C57/BL6 mice, homozygous for a mutant Nramp1 allele, Nramp1(G169D) , develop lethal infections. Restoration of Nramp1 (C57/BL6 Nramp1(G169) ) reestablishes resistance to S. Typhimurium; mice survive at least 3 to 4 weeks postinfection. Since many transgenic mouse strains are on a C57/BL6 genetic background, C57/BL6 Nramp1(G169) mice provide a model to examine host genetic determinants of resistance to infection. To further evaluate host immune response to S. Typhimurium, we performed comparative analyses of Sv129S6 and C57/BL6 Nramp1(G169) mice 3 weeks following oral S. Typhimurium infection. C57/BL6 Nramp1(G169) mice developed more severe inflammatory disease with splenic bacterial counts 1000-fold higher than Sv129S6 mice and relatively greater splenomegaly and blood neutrophil and monocyte counts. Infected C57/BL6 Nramp1(G169) mice developed higher proinflammatory serum cytokine and chemokine responses (interferon-, tumor necrosis factor-, interleukin [IL]-1, and IL-2 and monocyte chemotactic protein-1 and chemokine [C-X-C motif] ligand 1, respectively) and marked decreases in anti-inflammatory serum cytokine concentrations (IL-10, IL-4) compared with Sv129S6 mice postinfection. Splenic dendritic cells and macrophages in infected compared with control mice increased to a greater extent in C57/BL6 Nramp1(G169) mice than in Sv129S6 mice. Overall, data show that despite the Nramp1 gene present in both strains, C57/BL6 Nramp1(G169) mice develop more severe, Th1-skewed, acute inflammatory responses to S. Typhimurium infection compared with Sv129S6 mice. Both strains are suitable model systems for studying inflammation in the context of adaptive immunity. C1 [Brown, D. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. [Brown, D. E.; Stepanek, A.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Libby, S. J.; Fang, F. C.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Moreland, S. M.; McCoy, M. W.; Detweiler, C. S.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Brabb, T.] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA. [Fang, F. C.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Brown, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149 13th St, Boston, MA 02129 USA. EM dbrown31@partners.org OI Fang, Ferric/0000-0002-3243-110X FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [AI072492, AI095395, AI77629, AI39557] FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, award number AI072492 and AI095395 to CSD, and AI77629 and AI39557 to FCF. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 45 TC 12 Z9 13 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 EI 1544-2217 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 2013 VL 50 IS 5 BP 867 EP 876 DI 10.1177/0300985813478213 PG 10 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 245PI UT WOS:000326475500019 PM 23446432 ER PT J AU Jacobs, RL Harper, N He, W Rather, CG Castiblanco, J Carrillo, A Manoharan, M Avadhanam, N Liu, Y Ingale, P Andrews, CP Ramirez, DA Ahuja, SK AF Jacobs, R. L. Harper, N. He, W. Rather, C. G. Castiblanco, J. Carrillo, A. Manoharan, M. Avadhanam, N. Liu, Y. Ingale, P. Andrews, C. P. Ramirez, D. A. Ahuja, S. K. TI Evaluation of ultra-rush immunotherapy for Virginia live oak in a pollen challenge chamber identifies cytokine and transcriptional correlates of protection SO ALLERGY LA English DT Meeting Abstract CT World Allergy and Asthma Congress of the European-Academy-of-Allergy-and-Clinical-Immunology and World-Allergy-Organization CY JUN 22-26, 2013 CL Milan, ITALY SP European Acad Allergy & Clin Immunol, World Allergy Org C1 [Jacobs, R. L.; Rather, C. G.; Andrews, C. P.; Ramirez, D. A.] Biogen Res Chamber, San Antonio, TX USA. [Harper, N.; He, W.; Castiblanco, J.; Carrillo, A.; Manoharan, M.; Avadhanam, N.; Liu, Y.; Ingale, P.; Ahuja, S. K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Harper, N.; He, W.; Castiblanco, J.; Carrillo, A.; Manoharan, M.; Avadhanam, N.; Liu, Y.; Ingale, P.; Ahuja, S. K.] South Texas Vet Hlth Care Syst, Vet Adm Ctr Personalized Med, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2013 VL 68 SU 97 SI SI BP 20 EP 20 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 227VH UT WOS:000325142900044 ER PT J AU Long, AA Rahmaoui, A Rothman, KJ Guinan, EC Eisner, MD Bradley, MS Iribarren, C Chen, H Carrigan, G Rosen, K Szefler, SJ AF Long, A. A. Rahmaoui, A. Rothman, K. J. Guinan, E. C. Eisner, M. D. Bradley, M. S. Iribarren, C. Chen, H. Carrigan, G. Rosen, K. Szefler, S. J. TI The incidence of malignancy is similar among asthma patients treated with or without omalizumab: results from the long-term EXCELS study SO ALLERGY LA English DT Meeting Abstract CT World Allergy and Asthma Congress of the European-Academy-of-Allergy-and-Clinical-Immunology and World-Allergy-Organization CY JUN 22-26, 2013 CL Milan, ITALY SP European Acad Allergy & Clin Immunol, World Allergy Org C1 [Long, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rahmaoui, A.; Eisner, M. D.; Bradley, M. S.; Chen, H.; Carrigan, G.; Rosen, K.] Genentech Inc, San Francisco, CA 94080 USA. [Rothman, K. J.] RTI Hlth Solut, Res Triangle Pk, NC USA. [Guinan, E. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Iribarren, C.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA USA. [Szefler, S. J.] Natl Jewish Hlth, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2013 VL 68 SU 97 SI SI BP 39 EP 39 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 227VH UT WOS:000325142900083 ER PT J AU Patil, S Schneider, M Ma, A Brennan, A Alejos, A Shreffler, WG AF Patil, S. Schneider, M. Ma, A. Brennan, A. Alejos, A. Shreffler, W. G. TI Programmatic analysis of basophil activation testing SO ALLERGY LA English DT Meeting Abstract CT World Allergy and Asthma Congress of the European-Academy-of-Allergy-and-Clinical-Immunology and World-Allergy-Organization CY JUN 22-26, 2013 CL Milan, ITALY SP European Acad Allergy & Clin Immunol, World Allergy Org C1 [Patil, S.; Ma, A.; Brennan, A.; Alejos, A.; Shreffler, W. G.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schneider, M.] Buhlmann Labs, Schonenbuch, Switzerland. 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 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2013 VL 68 SU 97 SI SI BP 130 EP 131 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 227VH UT WOS:000325142901044 ER PT J AU Patil, SU Ogunniyi, AO Kubala, S Brennan, A Ma, A Moon, J Love, C Shreffler, WG AF Patil, S. U. Ogunniyi, A. O. Kubala, S. Brennan, A. Ma, A. Moon, J. Love, C. Shreffler, W. G. TI Induction of antigen-specific B cells using novel tetramer-based approach occurs early during peanut oral immunotherapy SO ALLERGY LA English DT Meeting Abstract CT World Allergy and Asthma Congress of the European-Academy-of-Allergy-and-Clinical-Immunology and World-Allergy-Organization CY JUN 22-26, 2013 CL Milan, ITALY SP European Acad Allergy & Clin Immunol, World Allergy Org C1 [Patil, S. U.; Brennan, A.; Ma, A.; Moon, J.; Shreffler, W. G.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ogunniyi, A. O.; Love, C.] MIT, Boston, MA USA. [Kubala, S.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2013 VL 68 SU 97 SI SI BP 469 EP 470 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 227VH UT WOS:000325142904139 ER PT J AU Joseph, J AF Joseph, Jacob TI Selenium and Cardiometabolic Health: Inconclusive Yet Intriguing Evidence SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Selenium; Cardiometabolic health; Selenoproteins ID CHRONIC HEART-FAILURE; SERUM SELENIUM; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; PLASMA SELENIUM; RISK; CARDIOMYOPATHY; CANCER; SUPPLEMENTATION; POPULATION AB Selenium is incorporated as the unique amino acid selenocysteine into selenoproteins, which regulate important biologic processes such as redox balance. The results of epidemiologic and clinical investigations are inconclusive regarding the relation of the plasma selenium level to cardiometabolic parameters and does not support the routine use of selenium supplements to prevent cancer or cardiovascular disease. Variability in the selenium status of the populations studied and lack of standardization of measures of selenium status may account for part of the confusion regarding selenium and cardiometabolic health. Another possibility is that differences in the effects of selenoproteins, as opposed to those of low-molecular-weight selenium compounds derived from in vivo metabolism of selenium, may explain the unusual phenomenon of a similar phenotype induced by both selenium deficiency and excess in experimental models and offer a plausible explanation for the lack of consistency in clinical studies. The epidemiologic, clinical, and experimental evidence, although inconclusive in terms of the precise relation of selenium to cardiometabolic health, is however very intriguing in terms of the urgent need for further mechanistic research to enable the clinical use of this potent micronutrient. C1 [Joseph, Jacob] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Joseph, Jacob] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Cardiol Sect 111, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM jjoseph16@partners.org FU National Institutes of Health [HL89734] FX Supported by the National Institutes of Health grant HL89734. NR 33 TC 6 Z9 6 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD SEP PY 2013 VL 346 IS 3 BP 216 EP 220 DI 10.1097/MAJ.0b013e3182638716 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 242MX UT WOS:000326247500009 PM 22990046 ER PT J AU Perkins, J Misleh, J AF Perkins, James, Jr. Misleh, Jamal TI Looking Beyond the Test SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Autoimmune hemolytic anemia; Direct antiglobulin test; Lactate dehydrogenase ID AUTOIMMUNE HEMOLYTIC-ANEMIA C1 [Perkins, James, Jr.] Temple Univ Hlth Syst, Philadelphia, PA USA. [Misleh, Jamal] Helen F Graham Canc Ctr, Christiana Care, Med Oncol Hematol Consultants PA, Newark, DE USA. RP Perkins, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St WAC 460, Boston, MA 02114 USA. EM albperk27@yahoo.com NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD SEP PY 2013 VL 346 IS 3 BP 234 EP 235 DI 10.1097/MAJ.0b013e31826af71a PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 242MX UT WOS:000326247500013 PM 23135231 ER PT J AU Land, AM Nelson, GA Bell, SG Denby, KJ Estrada, CA Willett, LL AF Land, Andrew M. Nelson, George A. Bell, Stephen G. Denby, Kara J. Estrada, Carlos A. Willett, Lisa L. TI Widening the Differential for Brain Masses in Human Immunodeficiency Virus-Positive Patients: Syphilitic Cerebral Gummata SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Syphilis; HIV; Neurosyphilis; Gumma ID HIV-INFECTION; NEUROSYPHILIS AB A 39-year-old man with newly diagnosed human immunodeficiency virus (HIV) infection was admitted with right-sided weakness, right-sided vision loss and slurred speech, which worsened over several weeks. Brain imaging revealed bilateral intraparenchymal ring-enhancing lesions and enhancement of the right optic nerve. Serological findings were positive for venereal disease research laboratory test, whereas the cerebrospinal fluid venereal disease research laboratory test was nonreactive. Brain biopsy suggested a diagnosis of syphilitic cerebral gummata, and the patient's improvement with penicillin and dexamethasone further supported this etiology. Syphilitic cerebral gummata have rarely been reported in patients with HIV infection. This patient demonstrates that cerebral gummata should be considered in the differential diagnosis in immunocompromised patients with characteristic brain masses, that HIV and syphilis often coexist with early neurosyphilis appearing more frequently in this patient population and that normal cerebrospinal fluid studies may not represent a true lack of syphilitic activity in HIV patients. C1 [Land, Andrew M.; Nelson, George A.; Bell, Stephen G.] Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, Birmingham, AL 35294 USA. [Denby, Kara J.] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA. [Estrada, Carlos A.; Willett, Lisa L.] Univ Alabama Birmingham, Birmingham Hosp, Div Gen Internal Med, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Qual Scholars Fellowship Program, Birmingham, AL USA. RP Land, AM (reprint author), Univ Alabama Birmingham, BDB 327,1720 2nd Ave South, Birmingham, AL 35294 USA. EM amland@uab.edu FU Department of Veterans Affairs National Quality Scholars Fellowship (VAQS); Department of Veterans Affairs Office of Academic Affiliations (OAA) FX The Department of Veterans Affairs National Quality Scholars Fellowship (VAQS) is funded by the Department of Veterans Affairs Office of Academic Affiliations (OAA). The opinions expressed in this article are those of the contributing authors alone and do not necessarily reflect the views, opinions or policies of the Department of Veterans Affairs. NR 13 TC 2 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD SEP PY 2013 VL 346 IS 3 BP 253 EP 255 DI 10.1097/MAJ.0b013e31828c9f22 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 242MX UT WOS:000326247500020 PM 23588265 ER PT J AU Forcione, DG AF Forcione, David G. TI On-site cytopathology for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses Is it Time to Make it Standard of Care? SO CANCER CYTOPATHOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Forcione, DG (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD SEP PY 2013 VL 121 IS 9 BP 471 EP 472 DI 10.1002/cncy.21341 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 217VL UT WOS:000324390300001 PM 24039158 ER PT J AU Yonker, LM Kinane, TB AF Yonker, Lael M. Kinane, T. Bernard TI Pediatric Interstitial Lung Disease Thyroid Transcription Factor-1 Mutations and Their Phenotype Potpourri SO CHEST LA English DT Editorial Material ID GENE; PROTEIN; EXPRESSION; MORPHOGENESIS; CELLS C1 [Yonker, Lael M.; Kinane, T. Bernard] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulmonol, Boston, MA 02114 USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulmonol, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM tbkinane@partners.org NR 12 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 EI 1931-3543 J9 CHEST JI Chest PD SEP PY 2013 VL 144 IS 3 BP 728 EP 730 DI 10.1378/chest.13-0550 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 241JC UT WOS:000326161700004 PM 24008946 ER PT J AU Kumetz, EA Goodson, JD AF Kumetz, Erik A. Goodson, John D. TI The Undervaluation of Evaluation and Management Professional Services The Lasting Impact of Current Procedural Terminology Code Deficiencies on Physician Payment SO CHEST LA English DT Article ID RELATIVE VALUE SCALE; PRIMARY-CARE; UNINTENDED CONSEQUENCES; WORK-INTENSITY; INCOME GAP; SPECIALTIES AB The Resource-Based Relative Value Scale (RBRVS) is fundamentally undermined by the following foundational errors: (1) The full range of office-based evaluation and management (E/M) activities are not captured by the Current Procedural Terminology (CPT) code choices, (2) it places relatively high values on procedural services, (3) there is no measure of intensity for complex outpatient E/M care, and (4) its maintenance and update have been delegated to select professional societies. Limitations imposed on the development of the RBRVS dating back to the early 1980s have not been corrected. The repertoire of codes for physician office-based E/M work must be expanded to create a new topology of choices with new outpatient code families with discrete service code levels, such as comprehensive outpatient consultation care, comprehensive outpatient primary care, and limited outpatient consultation care. Service code relative values must be based on representative samples and reliable survey data, draw from the broader literature on work intensity, and be developed with accountable and representative professional engagement. C1 [Kumetz, Erik A.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Goodson, John D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Internal Med Unit,Dept Med, Boston, MA USA. [Goodson, John D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, John D Stoeckle Ctr Primary Care Innovat, Boston, MA USA. RP Goodson, JD (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. EM JGoodson1@Partners.org NR 25 TC 6 Z9 6 U1 1 U2 8 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2013 VL 144 IS 3 BP 740 EP 745 DI 10.1378/chest.13-0381 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 241JC UT WOS:000326161700009 PM 23764970 ER PT J AU Bersohn, MM Turner, MP Traiger, GL Frost, AE Shapiro, S AF Bersohn, Malcolm M. Turner, Michelle P. Traiger, Glenna L. Frost, Adaani E. Shapiro, Shelley TI Systemic BP and Heart Rate as Prognostic Indicators in Pulmonary Arterial Hypertension SO CHEST LA English DT Article ID REVEAL REGISTRY; DISEASE MANAGEMENT; FAILURE; PREDICTORS; INSIGHTS; OUTCOMES; ASSOCIATION; GUIDELINES; DIAGNOSIS; MORTALITY AB Background: Heart rate (HR) and systolic BP (SBP) are significant multivariate predictors of survival in patients with pulmonary arterial hypertension (PAH) as part of a 19-element formula. To what extent HR and BP alone predict survival and future hospitalization in patients with PAH is unknown. Methods: We analyzed data from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry), a prospective, observational study of patients with PAH. Patients were analyzed by quintile (Q) according to values of HR, SBP, and SBP/HR. Kaplan-Meier curves were calculated by Q for survival and freedom from hospitalization. Results: For patients in the worst Q, 1-year survival after enrollment was 85% +/- 2% for SBP, 86% +/- 2% for HR, and 84% +/- 2% for SBP/HR vs 91% +/- 1% for the middle three Qs (P < .001). Hospitalization occurred more frequently than mortality but with a similar pattern among Qs. One-year survival after first follow-up of patients in the worst Q for change (Delta) in SBP since enrollment was 85% +/- 2% (P = .004), 86% +/- 2% for Delta HR (P = .12), and 84% +/- 2% for Delta SBP/HR (P = .024) vs the middle three Qs (Delta SBP: 91% +/- 1%; Delta HR: 90% +/- 1%; Delta SBP/HR: 90% +/- 1%). Conclusions: Changes in vital signs from enrollment to first follow-up were less predictive of mortality than the values of vital-sign parameters at either enrollment or first follow-up. HR, SBP, and SBP/HR at enrollment identified high-risk groups with survival differences of 5% to 7% and freedom from hospitalization differences of 9% to 11% vs lower-risk groups. SBP/HR defines the highest-risk group, including most of the high-risk patients defined by HR and SBP separately. C1 [Bersohn, Malcolm M.; Shapiro, Shelley] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bersohn, Malcolm M.; Shapiro, Shelley] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Turner, Michelle P.] ICON Late Phase & Outcomes Res, San Francisco, CA USA. [Traiger, Glenna L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Frost, Adaani E.] Baylor Coll Med, Houston, TX 77030 USA. RP Bersohn, MM (reprint author), VA Greater Angeles Healthcare Syst, Cardiol 111E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mbersohn@ucla.edu FU Cotherix Inc FX Funding and support for the REVEAL Registry were provided by Cotherix Inc, and its affiliate Actelion Pharmaceuticals US Inc. NR 15 TC 3 Z9 3 U1 3 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 EI 1931-3543 J9 CHEST JI Chest PD SEP PY 2013 VL 144 IS 3 BP 959 EP 965 DI 10.1378/chest.12-2572 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 241JC UT WOS:000326161700034 PM 23598723 ER PT J AU Wiggs, JL Hauser, MA Abdrabou, W Allingham, RR Budenz, DL DelBono, E Friedman, DS Kang, JH Gaasterland, D Gaasterland, T Lee, RK Lichter, PR Loomis, S Liu, YT McCarty, C Medeiros, FA Moroi, SE Olson, LM Realini, A Richards, JE Rozsa, FW Schuman, JS Singh, K Stein, JD Vollrath, D Weinreb, RN Wollstein, G Yaspan, BL Yoneyama, S Zack, D Zhang, K Pericak-Vance, M Pasquale, LR Haines, JL AF Wiggs, Janey L. Hauser, Michael A. Abdrabou, Wael Allingham, Robert Rand Budenz, Donald L. DelBono, Elizabeth Friedman, David S. Kang, Jae H. Gaasterland, Douglas Gaasterland, Terry Lee, Richard K. Lichter, Paul R. Loomis, Stephanie Liu, Yutao McCarty, Cathy Medeiros, Felipe A. Moroi, Sayoko E. Olson, Lana M. Realini, Anthony Richards, Julia E. Rozsa, Frank W. Schuman, Joel S. Singh, Kuldev Stein, Joshua D. Vollrath, Douglas Weinreb, Robert N. Wollstein, Gadi Yaspan, Brian L. Yoneyama, Sachiko Zack, Don Zhang, Kang Pericak-Vance, Margaret Pasquale, Louis R. Haines, Jonathan L. TI The NEIGHBOR Consortium Primary Open-Angle Glaucoma Genome-wide Association Study: Rationale, Study Design, and Clinical Variables SO JOURNAL OF GLAUCOMA LA English DT Article DE primary open-angle glaucoma; genome-wide association study; genetics ID BASE-LINE CHARACTERISTICS; CENTRAL CORNEAL THICKNESS; SYNTHASE GENE VARIANTS; FACTOR-H POLYMORPHISM; BALTIMORE EYE SURVEY; BEAVER-DAM EYE; MACULAR DEGENERATION; SUSCEPTIBILITY LOCUS; REFRACTIVE ERROR; COMMON VARIANTS AB Primary open-angle glaucoma (POAG) is a common disease with complex inheritance. The identification of genes predisposing to POAG is an important step toward the development of novel gene-based methods of diagnosis and treatment. Genome-wide association studies (GWAS) have successfully identified genes contributing to complex traits such as POAG however, such studies frequently require very large sample sizes, and thus, collaborations and consortia have been of critical importance for the GWAS approach. In this report we describe the formation of the NEIGHBOR consortium, the harmonized case control definitions used for a POAG GWAS, the clinical features of the cases and controls, and the rationale for the GWAS study design. C1 [Wiggs, Janey L.; Hauser, Michael A.; Abdrabou, Wael; Allingham, Robert Rand; Budenz, Donald L.; DelBono, Elizabeth; Friedman, David S.; Kang, Jae H.; Gaasterland, Douglas; Gaasterland, Terry; Lee, Richard K.; Lichter, Paul R.; Loomis, Stephanie; Liu, Yutao; McCarty, Cathy; Medeiros, Felipe A.; Moroi, Sayoko E.; Olson, Lana M.; Realini, Anthony; Richards, Julia E.; Rozsa, Frank W.; Schuman, Joel S.; Singh, Kuldev; Stein, Joshua D.; Vollrath, Douglas; Weinreb, Robert N.; Wollstein, Gadi; Yaspan, Brian L.; Yoneyama, Sachiko; Zack, Don; Zhang, Kang; Pericak-Vance, Margaret; Pasquale, Louis R.; Haines, Jonathan L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Schuman, Joel/K-7304-2012; OI Schuman, Joel/0000-0002-8885-3766; Rozsa, Frank/0000-0002-1378-7020; Zack, Don/0000-0002-7966-1973 FU National Eye Institute through ARRA [3R01EY015872-05S1, 3R01EY019126-02S1]; NIH [EY015543, EY006827, HL73042, HL073389, EY13315, CA87969, CA49449, CA55075, EY009149, HG004608, EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178, RR015574, EY015872, EY010886, EY009847, EY011008, EY144428, EY144448, EY18660, T32EY021453]; Harvard Glaucoma Center for Excellence; Margolis Fund; Glaucoma Research Foundation; National Glaucoma Research of American Health Assistance Foundation; The Glaucoma Foundation; Research to Prevent Blindness FX Collecting and processing samples for the NEIGHBOR data set was supported by the National Eye Institute through ARRA grants 3R01EY015872-05S1 (J.L.W.) and 3R01EY019126-02S1 (M. A. H.). Funding for the collection of cases and controls was provided by NIH grants: EY015543 (R. R. A.), EY006827 (Gaasterland), HL73042 (Goldschmidt), HL073389 (Hauser, E); EY13315 (M. A. H.); CA87969 (J.H.K.), CA49449 (J.H.K.), CA55075 (J.H.K.), EY009149 (P. R. L.), HG004608 (C. M.), EY008208 (F. A. M.), EY015473 (L. R. P.), EY012118 (M. P.-V.), EY015682 (A. R.), EY011671 (J.E.R.), EY09580 (J.E.R.), EY013178 (J.S.S.), RR015574 (Spirou), EY015872 (J.L.W.), EY010886 (J.L.W.), EY009847 (J.L.W.), EY011008 (Zangwill), EY144428 (K.Z.), EY144448 (K.Z.), EY18660 (K.Z.). J.L.W. and L. R. P. are also supported by the Harvard Glaucoma Center for Excellence, and the Margolis Fund. B.L.Y. is supported in part by NIH grant T32EY021453. Y.L. is supported in part by the Glaucoma Research Foundation, National Glaucoma Research of American Health Assistance Foundation, and The Glaucoma Foundation. J.L.W., L. R. P., and J.E.R. are supported by Research to Prevent Blindness. A full listing of collaborators for GLAUGEN can be found in dbGaP at The POAG Genes and Environment (GLAUGEN) Study. Study Accession: phs000308.v1.p1. In addition, Drs. Cynthia Grosskreutz, Teresa Chen, Douglas Rhee, Tim Johnson, Colm O'Brien, Ms Katy Downs, and the CIGTS investigators and AGIS investigators helped identify patients and controls for these studies. NR 56 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD SEP PY 2013 VL 22 IS 7 BP 517 EP 525 DI 10.1097/IJG.0b013e31824d4fd8 PG 9 WC Ophthalmology SC Ophthalmology GA 217UU UT WOS:000324388300003 PM 22828004 ER PT J AU Alasil, T Wang, KD Keane, PA Lee, H Baniasadi, N Boer, JF Chen, TC AF Alasil, Tarek Wang, Kaidi Keane, Pearse A. Lee, Hang Baniasadi, Neda de Boer, Johannes F. Chen, Teresa C. TI Analysis of Normal Retinal Nerve Fiber Layer Thickness by Age, Sex, and Race Using Spectral Domain Optical Coherence Tomography SO JOURNAL OF GLAUCOMA LA English DT Article DE spectralis; spectral domain optical coherence tomography; retinal nerve fiber layer ID GLAUCOMATOUS EYES; LINEAR-MODEL; STRATUS OCT; TIME-DOMAIN; VISUAL FUNCTION; NORMAL-CHILDREN; HEALTHY EYES; HIGH-SPEED; ISNT RULE; DISC SIZE AB Purpose: To determine the effects of age, sex, and race on the retinal nerve fiber layer (RNFL) in the normal human eye as measured by the spectral domain optical coherence tomography (SD-OCT) Spectralis machine (Heidelberg Engineering). Methods: Peripapillary SD-OCT RNFL thickness measurements were determined in normal subjects seen at a university-based clinic. One randomly selected eye per subject was used for analysis in this cross-sectional study. Multiple regression analysis was applied to assess the effects of age, sex, ethnicity, and mean refractive error on peripapillary RNFL thickness. Results are expressed as means +/- SD wherever applicable. Results: The study population consisted of 190 healthy participants from 9 to 86 years of age. Of the 190 participants, 62 (33%) were men, 125 (66%) Caucasians, 26 (14%) African Americans, 14 (7%) Hispanics, 16 (8%) Asians, and 9 (5%) other races. The mean RNFL thickness for the normal population studied was 97.3 +/- 9.6 mu m. Normal RNFL thickness values follow the ISNT rule with decreasing RNFL thickness values starting from the thickest quadrant inferiorly to the thinnest quadrant temporally: inferior quadrant (126 +/- 15.8), superior quadrant (117.2 +/- 16.13), nasal quadrant (75 +/- 13.9), and temporal quadrant (70.6 +/- 10.8 mu m). Thinner RNFL measurements were associated with older age (P<0.001); being Caucasian, versus being either Hispanic or Asian (P=0.02 and 0.009, respectively); or being more myopic (P<0.001). For every decade of increased age, mean RNFL thickness measured thinner by approximately 1.5 mu m (95% confidence interval, 0.24-0.07). Comparisons between ethnic groups revealed that Caucasians had mean RNFL values (96 +/- 9.2 mu m) slightly thinner than those of Hispanics (102.9 +/- 11 mu m; P=0.02) or Asians (100.7 +/- 8.5 mu m; P=0.009). African Americans RNFL values (99.2 +/- 10.2 mu m) were not significantly different when compared with Caucasians. There was no relationship between RNFL thickness and sex. Conclusions: The thickest RNFL measurements were found in the inferior quadrant, followed by the superior, nasal, and temporal quadrants (ISNT rule applied to the RNFL). Thinner RNFL measurements were associated with older age and increasing myopia. Caucasians tend to have thinner RNFL values when compared with Hispanics and Asians. SD-OCT analysis of the normal RNFL showed results similar to time domain OCT studies. C1 [Alasil, Tarek; Baniasadi, Neda; Chen, Teresa C.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Wang, Kaidi] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Lee, Hang] Harvard Catalyst Program, Boston, MA USA. [Keane, Pearse A.] Moorfields Eye Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res Biomed Res Ctr Ophthalmol, London, England. [Keane, Pearse A.] UCL, Inst Ophthalmol, London, England. [de Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys & Astron, Amsterdam, Netherlands. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU Department of Health's National Institute for Health Research Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology; Nidek; Harvard Catalyst; The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758] FX P.A.K. receives funding from the Department of Health's National Institute for Health Research Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology. J.F.d.B. has received past research support from Nidek. Also, J.F.d.B. has patents in spectral domain OCT technology. This work was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centers). NR 63 TC 63 Z9 65 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD SEP PY 2013 VL 22 IS 7 BP 532 EP 541 DI 10.1097/IJG.0b013e318255bb4a PG 10 WC Ophthalmology SC Ophthalmology GA 217UU UT WOS:000324388300005 PM 22549477 ER PT J AU Alasil, T Jakobiec, FA Zakka, FR Gardiner, M Chen, TC AF Alasil, Tarek Jakobiec, Frederick A. Zakka, Fouad R. Gardiner, Matthew Chen, Teresa C. TI Inadvertent Filtering Bleb Due to Corneal Stromal Wick Syndrome SO JOURNAL OF GLAUCOMA LA English DT Article DE tissue incarceration; hypotony; corneal stroma; glaucoma; unplanned filtering bleb; cataract surgery ID CATARACT-SURGERY AB We report a unique case in which an inadvertent filtering bleb was created after a complicated cataract surgery through an unusual mechanism: an internal fragment of corneal stroma, which was still attached at one end of the clear corneal wound, was pushed into the anterior chamber, became inadvertently entrapped in the wound, and served as a wick to prevent complete healing. C1 [Alasil, Tarek; Chen, Teresa C.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Gardiner, Matthew] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Comprehens Ophthalmol Serv, Boston, MA 02114 USA. [Alasil, Tarek; Jakobiec, Frederick A.; Zakka, Fouad R.; Gardiner, Matthew; Chen, Teresa C.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chen, TC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu OI Gardiner, Matthew/0000-0002-8864-2379 NR 8 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD SEP PY 2013 VL 22 IS 7 BP e14 EP e15 DI 10.1097/IJG.0b013e3182a07604 PG 2 WC Ophthalmology SC Ophthalmology GA 217UU UT WOS:000324388300001 PM 23872620 ER PT J AU Kramer, H Dugas, L Rosas, SE AF Kramer, Holly Dugas, Lara Rosas, Sylvia E. TI Race and the Insulin Resistance Syndrome SO SEMINARS IN NEPHROLOGY LA English DT Review DE Metabolic syndrome; African Americans; racial differences; diabetes ID BODY-MASS INDEX; CHRONIC KIDNEY-DISEASE; FATTY LIVER-DISEASE; NUTRITION EXAMINATION SURVEY; ADIPOSE-TISSUE DISTRIBUTION; AFRICAN-AMERICAN WOMEN; STAGE RENAL-DISEASE; APOLIPOPROTEIN L1 APOL1; 3RD NATIONAL-HEALTH; 3 GENE PNPLA3 AB Type 2 diabetes remains an important cause of morbidity and mortality. The metabolic syndrome affects 25% of the adult US population based on the Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults from the National Cholesterol Education Program. Knowledge on the impact of obesity on metabolic health parameters has increased greatly over the past decade. This review discusses the limitations of the National Cholesterol Education Program metabolic syndrome definition and the racial disparities in the clinical presentation of the insulin resistance syndrome. We also examine the current literature with particular emphasis on albuminuria, nonalcoholic fatty liver disease, and intramyocellular lipid content. This review explores potential environmental and genetic reasons for differences in the manifestation of insulin resistance across racial/ethnic groups and highlights several promising areas for further study. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kramer, Holly; Dugas, Lara] Loyola Univ, Dept Publ Hlth Sci, Div Nephrol & Hypertens, Maywood, IL 60153 USA. [Kramer, Holly; Dugas, Lara] Loyola Univ, Dept Med, Div Nephrol & Hypertens, Maywood, IL 60153 USA. [Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kramer, H (reprint author), Loyola Univ, Dept Publ Hlth Sci, Hlth Sci Campus,2160 S 1st Ave, Maywood, IL 60153 USA. EM hkramer@lumc.edu OI Kramer, Holly/0000-0002-6374-837X NR 132 TC 2 Z9 2 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 EI 1558-4488 J9 SEMIN NEPHROL JI Semin. Nephrol. PD SEP PY 2013 VL 33 IS 5 BP 457 EP 467 DI 10.1016/j.semnephrol.2013.07.007 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 240ZB UT WOS:000326135100007 PM 24119851 ER PT J AU Inabnet, WB Bour, E Carlin, AM Clements, R Finks, J Hutter, M Joyce, C Marley, K Moran, J Morton, J Reavis, K Richardson, WS Satgunam, S AF Inabnet, William B., III Bour, Eric Carlin, Arthur M. Clements, Ronald Finks, Jonathan Hutter, Matt Joyce, Christopher Marley, Kim Moran, Joe Morton, John Reavis, Kevin Richardson, William S. Satgunam, Shean TI Joint task force recommendations for credentialing of bariatric surgeons SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Editorial Material C1 [Inabnet, William B., III] Ichan Sch Med Mt Sinai, New York, NY USA. [Bour, Eric] Greenville Hlth Systenz, Hillcrest Mem Hosp, Greenville, SC USA. [Carlin, Arthur M.] Wayne State Univ, Detroit, MI USA. [Clements, Ronald] Vanderbilt Univ, Nashville, TN 37235 USA. [Finks, Jonathan] Univ Michigan, Ann Arbor, MI 48109 USA. [Hutter, Matt] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Joyce, Christopher] BMI Surg, New Lenox, IL USA. [Marley, Kim] Windber Med Ctr, Windber, PA USA. [Moran, Joe] Raleigh Ctr Weight Loss Surg & Rex Healthcare, Raleigh, NC USA. [Morton, John] Stanford Sch Med, Stanford, CA USA. [Reavis, Kevin] Oregon Clin, Div Gastrointestinal & Minimally Invas Surg, Portland, OR USA. [Richardson, William S.] Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA. [Satgunam, Shean] Michigan State Univ, E Lansing, MI 48824 USA. RP Inabnet, WB (reprint author), Ichan Sch Med Mt Sinai, New York, NY USA. RI Richardson, William/D-3569-2011 NR 2 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD SEP-OCT PY 2013 VL 9 IS 5 BP 595 EP 597 DI 10.1016/j.soard.2013.06.014 PG 3 WC Surgery SC Surgery GA 236GG UT WOS:000325782900001 PM 24079897 ER PT J AU Yusin, JS Klaustermeyer, W Simmons, CW Baum, M AF Yusin, J. S. Klaustermeyer, W. Simmons, C. W. Baum, M. TI Desensitization in patients with beta-lactam drug allergy SO ALLERGOLOGIA ET IMMUNOPATHOLOGIA LA English DT Article DE Beta-lactam antibiotic; Hypersensitivity; Desensitization ID PENICILLIN ALLERGY; IMMEDIATE HYPERSENSITIVITY; CLINICAL HISTORY; CROSS-REACTIVITY; TOLERABILITY; EXPERIENCE; REAGENTS; IMIPENEM AB Background: Patients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients' histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization. Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options. This paper reviews the safety of beta-lactam desensitization. Objective: To perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. Methods: A retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed. Results: A total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36-92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full therapeutic courses of their antibiotic. Conclusion: Beta-lactam antibiotic sensitivity continues to present a challenging problem for physicians. Patients with drug resistant infections who are unable to obtain skin testing or who test positive to skin tests may need either a challenge or desensitization. Desensitization, saved for those with a convincing beta-lactam hypersensitivity history is often the choice of last resort given the associated cost and risk of anaphylaxis. However, once desensitization is complete, patients are usually able to tolerate full doses of antibiotics for full treatment length with minimal side effects. Published by Elsevier Espana, S.L. on behalf of SEICAP. C1 [Yusin, J. S.; Simmons, C. W.; Baum, M.] Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. [Klaustermeyer, W.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Yusin, JS (reprint author), Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. EM Joseph.Yusin2@va.gov FU Department of Veterans Affairs FX This material is based upon work supported by the Department of Veterans Affairs. NR 23 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0301-0546 EI 1578-1267 J9 ALLERGOL IMMUNOPATH JI Allergol. Immunopath. PD SEP-OCT PY 2013 VL 41 IS 5 BP 298 EP 303 DI 10.1016/j.aller.2012.06.003 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 237BL UT WOS:000325843100004 PM 23177979 ER PT J AU Clark, KB AF Clark, Kevin B. TI New Therapeutic Bearings for Repositioned Drugs SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Editorial Material C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. RP Clark, KB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, 4229 SE Harney St, Los Angeles, CA 90073 USA. NR 0 TC 3 Z9 3 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD SEP PY 2013 VL 13 IS 18 BP 2281 EP 2282 PG 2 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 238EX UT WOS:000325926500006 PM 24059466 ER PT J AU Clark, KB Eisenstein, EM Krahl, SE AF Clark, Kevin B. Eisenstein, Edward M. Krahl, Scott E. TI Calcium Antagonists: A Ready Prescription for Treating Infectious Diseases? SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Antibiotic tolerance or resistance; antimicrobial drugs; biotechnology; disease transmission and virulence; microbial pathogens and parasites; pharmaceuticals ID WORLD-HEALTH-ORGANIZATION; LEISHMANIA L. CHAGASI; ANTIMICROBIAL AGENTS; ANTIBIOTIC-RESISTANCE; CA2+ CHANNEL; OLD DRUGS; IN-VITRO; PROTOZOAN PARASITES; FILAMENTOUS FUNGUS; CANDIDA-ALBICANS AB Emergence of new and medically resistant pathogenic microbes continues to escalate toward worldwide public health, wild habitat, and commercial crop and livestock catastrophes. Attempts at solving this problem with sophisticated modern biotechnologies, such as smart vaccines and microbicidal and microbistatic drugs that precisely target parasitic bacteria, fungi, and protozoa, remain promising without major clinical and industrial successes. However, discovery of a more immediate, broad spectrum prophylaxis beyond conventional epidemiological approaches might take no longer than the time required to fill a prescription at your neighborhood pharmacy. Findings from a growing body of research suggest calcium antagonists, long approved and marketed for various human cardiovascular and neurological indications, may produce safe, efficacious antimicrobial effects. As a general category of drugs, calcium antagonists include compounds that disrupt passage of Ca2+ molecules across cell membranes and walls, sequestration and mobilization of free intracellular Ca2+, and downstream binding proteins and sensors of Ca2+-dependent regulatory pathways important for proper cell function. Administration of calcium antagonists alone at current therapeutically relevant doses and schedules, or with synergistic compounds and additional antimicrobial medications, figures to enhance host immunoprotection by directly altering pathogen infection sequences, life cycles, homeostasis, antibiotic tolerances, and numerous other infective, survival, and reproductive processes. Short of being miracle drugs, calcium antagonists are welcome old drugs with new tricks capable of controlling some of the most virulent and pervasive global infectious diseases of plants, animals, and humans, including Chagas' disease, malaria, and tuberculosis. C1 [Eisenstein, Edward M.; Krahl, Scott E.] Vet Affairs Greater Los Angeles Hlth Care Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. [Krahl, Scott E.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. RP Clark, KB (reprint author), 4229 S E Harney St, Portland, OR 97206 USA. EM kbclarkphd@yahoo.com NR 143 TC 3 Z9 3 U1 1 U2 14 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD SEP PY 2013 VL 13 IS 18 BP 2291 EP 2305 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 238EX UT WOS:000325926500008 PM 24059464 ER PT J AU Garvey, WT AF Garvey, W. Timothy TI NEW TOOLS FOR WEIGHT-LOSS THERAPY ENABLE A MORE ROBUST MEDICAL MODEL FOR OBESITY TREATMENT: RATIONALE FOR A COMPLICATIONS-CENTRIC APPROACH SO ENDOCRINE PRACTICE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTION; BODY-MASS INDEX; CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; LIPOPROTEIN SUBCLASS PROFILE; TOPIRAMATE EXTENDED-RELEASE; TYPE-2 DIABETES-MELLITUS; OBSTRUCTIVE SLEEP-APNEA; CARDIOVASCULAR RISK; METABOLIC SYNDROME AB Objective: Recent advances in lifestyle intervention programs, pharmacotherapy, and bariatric surgery have enabled the development of medical models for the treatment of obesity. Regarding pharmacotherapy, in 2012 the U.S. Food and Drug Administration approved two new effective and safe weight-loss medications, phentermine/topiramate extended release and lorcaserin, which has greatly augmented options for medically assisted weight loss. Methods: The rationale for advantages of a complications- centric medical model over current body mass index (BMI)-centric indications for therapy is examined. Results: Currently, the baseline BMI level is the principle determinant of indications for obesity treatment using medication and surgery. However, the BMI-centric approach fails to target therapy to those obese patients who will benefit most from weight loss. In contrast, a complications- centric medical model is proposed that will earmark the modality and intensity of the therapeutic intervention based on the presence and severity of complications that can be ameliorated by weight loss. Conclusion: The complications-centric approach to "medicalizing" obesity care employs weight loss primarily as a tool to treat obesity-related complications and promotes the optimization of health outcomes, the benefit/ risk ratio, and the cost-effectiveness of therapy. C1 [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Webb 232,1720 2nd Ave South, Birmingham, AL 35294 USA. EM garveyt@uab.edu FU Weight Watchers International Inc.; Amylin; Merck FX Dr. Garvey is an advisor for Alkermes Plc, Daiichi-Sankyo Inc, LipoScience, VIVUS Inc, Janssen Pharmaceuticals, Novo Nordisk, Eisai, AstraZeneca/Bristol-Myers-Squibb, and Tethys. He is a speaker for Merck & Company and Amylin Pharmaceuticals Inc and holds stock in Bristol-Myers Squibb Company, Isis/Genzyme, Merck, Pfizer Inc, Eli Lilly and Company, and VIVUS Inc. He has received research support from Amylin, Merck, and Weight Watchers International Inc. NR 77 TC 16 Z9 16 U1 0 U2 7 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD SEP-OCT PY 2013 VL 19 IS 5 BP 864 EP 874 DI 10.4158/EP13263.RA PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 235WC UT WOS:000325750800022 PM 24014010 ER PT J AU Dording, C Cassiello, C King, F Pencina, M Fava, M Mischoulon, D AF Dording, Christina Cassiello, Clair King, Franklin Pencina, Michael Fava, Maurizio Mischoulon, David TI The effects of aripiprazole on the subscales of the Kellner Symptom Questionnaire in treatment resistant depression SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE aripiprazole; augmentation; treatment resistant depression ID GENERALIZED ANXIETY DISORDER; SEROTONIN REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; DOUBLE-BLIND; ANTIDEPRESSANT THERAPY; INADEQUATE RESPONSE; CONTROLLED-TRIALS; BIPOLAR DISORDER; CASE SERIES; AUGMENTATION AB We have recently examined the efficacy of low-dose aripiprazole augmentation for major depressive disorder (MDD), with modest nonsignificant benefit found. In a secondary investigation, we examined whether aripiprazole resulted in improvement in four subscales (depression, anxiety, somatic symptoms, and hostility) of the Kellner Symptom Questionnaire (KSQ). We reanalyzed data from the main outcome study on 221 MDD patients with inadequate response to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. Patients were randomized, using the sequential parallel comparison design, into two 30-day phases, as follows: drug/drug (aripiprazole 2 mg/day in phase 1, aripiprazole 5 mg/day in phase 2), placebo/drug (placebo in phase 1, aripiprazole 2 mg/day in phase 2), or placebo/placebo (placebo in both phases). We examined changes in the KSQ score from baseline to endpoint on the basis of the subscaled Well-being and Reversal Distressed Anxiety Subscales. The score for the KSQ depression subscale improved from baseline to the end of follow-up, with a significant advantage for aripiprazole over placebo (P=0.0327). Although improvement was also observed in the anxiety and hostility scales, neither attained a significant advantage over placebo; no significant change was observed for the somatization subscale. Aripiprazole augmentation resulted in a significant improvement compared with placebo augmentation only in the depression subscale of the KSQ; however, the low dose may not have been enough to have an impact on the anxiety and hostility scales. The good tolerability of the low dose may have resulted in the absence of worsening of somatic symptoms. Prospective studies are needed to better characterize the impact of low doses of aripiprazole augmentation on different manifestations of MDD. C1 [Dording, Christina; Cassiello, Clair; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Pencina, Michael] Boston Univ, Dept Biostat, Sch Mental Hlth, Boston, MA 02215 USA. [King, Franklin] Univ Massachusetts, Med Ctr, Worcester, MA USA. RP Dording, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM cdording@partners.org FU Bristol-Myers Squibb FX The study from which data for the present paper were taken [A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy (ADT) among depressed outpatients with inadequate response to prior ADT (ADAPT-A Study)] was an investigator-initiated study supported by Bristol-Myers Squibb, which provided blinded study medication. Bristol-Myers Squibb did not have a role in the study design, collection, analysis, or interpretation of data in the ADAPT-A Study. Bristol-Myers Squibb had no role in the writing of the present paper or the decision to submit the paper for publication. The present paper was submitted for review by Bristol-Myers Squibb before submission to the Journal of Psychiatric Research. NR 31 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 EI 1473-5857 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 2013 VL 28 IS 5 BP 238 EP 244 DI 10.1097/YIC.0b013e32836220df PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 240HT UT WOS:000326086800003 PM 23764521 ER PT J AU Thakurathi, N Stock, S Oppenheim, CE Borba, CPC Vincenzi, B Seidman, LJ Stone, WS Henderson, DC AF Thakurathi, Neelam Stock, Shannon Oppenheim, Claire E. Borba, Christina P. C. Vincenzi, Brenda Seidman, Larry J. Stone, William S. Henderson, David C. TI Open-label pilot study on vitamin D-3 supplementation for antipsychotic-associated metabolic anomalies SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE antipsychotic; diabetes; hyperlipidemia; hypertension; metabolic syndrome; vitamin D ID PLACEBO-CONTROLLED TRIAL; CORONARY HEART-DISEASE; GLUCOSE-TOLERANCE TEST; MINIMAL MODEL ANALYSIS; D DEFICIENCY; WEIGHT-GAIN; ATYPICAL ANTIPSYCHOTICS; 1,25-DIHYDROXYVITAMIN D-3; SERUM CONCENTRATIONS; CARDIOVASCULAR RISK AB Previous studies have linked vitamin D deficiency to hypertension, dyslipidemia, diabetes mellitus, and cardiovascular disease. The aim of this study was to investigate the short-term effects of vitamin D-3 supplementation on weight and glucose and lipid metabolism in antipsychotic-treated patients. A total of 19 schizophrenic or schizoaffective patients (BMI>27 kg/m(2)) taking atypical antipsychotics were recruited and dispensed a 2000 IU daily dose of vitamin D-3. On comparing baseline with week 8 (study end) results, we found a statistically significant increase in vitamin D-3 and total vitamin D levels but no statistically significant changes in weight, glucose, or lipids measurements. Patients whose vitamin D-3 level at week 8 was 30 ng/ml or more achieved a significantly greater decrease in total cholesterol levels compared with those whose week 8 vitamin D-3 measurement was less than 30 ng/ml. These results suggest that a randomized trial with a longer follow-up period would be helpful in further evaluating the effects of vitamin D-3 on weight, lipid metabolism, and on components of metabolic syndrome in antipsychotic-treated patients. C1 [Thakurathi, Neelam; Oppenheim, Claire E.; Borba, Christina P. C.; Vincenzi, Brenda; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA. [Borba, Christina P. C.; Seidman, Larry J.; Stone, William S.; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stock, Shannon] Coll Holy Cross, Dept Math & Comp Sci, Worcester, MA 01610 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org FU Commonwealth of Massachusetts grant, Center of Excellence in Clinical Neuroscience and Psychopharmacological Research [SCDMH82101008006] FX This study was supported in part by the Commonwealth of Massachusetts grant (SCDMH82101008006), Center of Excellence in Clinical Neuroscience and Psychopharmacological Research (Seidman, Principal Investigator). NR 63 TC 5 Z9 6 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 EI 1473-5857 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 2013 VL 28 IS 5 BP 275 EP 282 DI 10.1097/YIC.0b013e3283628f98 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 240HT UT WOS:000326086800008 PM 23694999 ER PT J AU Loewenstein, G Friedman, JY McGill, B Ahmad, S Linck, S Sinkula, S Beshears, J Choi, JJ Kolstad, J Laibson, D Madrian, BC List, JA Volpp, KG AF Loewenstein, George Friedman, Joelle Y. McGill, Barbara Ahmad, Sarah Linck, Suzanne Sinkula, Stacey Beshears, John Choi, James J. Kolstad, Jonathan Laibson, David Madrian, Brigitte C. List, John A. Volpp, Kevin G. TI Consumers' misunderstanding of health insurance SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Insurance; Behavioral economics; Simplification ID INFORMATION; MARKETS; CHOICE; COVERAGE AB We report results from two surveys of representative samples of Americans with private health insurance. The first examines how well Americans understand, and believe they understand, traditional health insurance coverage. The second examines whether those insured under a simplified all-copay insurance plan will be more likely to engage in cost-reducing behaviors relative to those insured under a traditional plan with deductibles and coinsurance, and measures consumer preferences between the two plans. The surveys provide strong evidence that consumers do not understand traditional plans and would better understand a simplified plan, but weaker evidence that a simplified plan would have strong appeal to consumers or change their healthcare choices. (C) 2013 Elsevier B.V. All rights reserved. C1 [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Friedman, Joelle Y.] Univ Penn, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [McGill, Barbara] Colchester Consulting Grp, Glencoe, IL 60022 USA. [Linck, Suzanne] Humana, Strateg Consultant Product Dev Small Business, Green Bay, WI 54344 USA. [Sinkula, Stacey] Humana, Managing Actuary Small Business, Green Bay, WI 54344 USA. [Beshears, John] Stanford Grad Sch Business, Stanford, CA 94305 USA. [Choi, James J.] Yale Sch Management, New Haven, CT 06520 USA. [Kolstad, Jonathan] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Laibson, David] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA. [Madrian, Brigitte C.] Harvard Univ, Cambridge, MA 02138 USA. [List, John A.] Univ Chicago, Chicago, IL USA. [Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Volpp, Kevin G.] Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Davis, CA USA. [Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Ahmad, Sarah] Dev Humana, Commercial Product, Louisville, KY 40202 USA. RP Loewenstein, G (reprint author), Carnegie Mellon Univ, 5000 Forbes Ave,319 C Porter Hall, Pittsburgh, PA 15213 USA. EM gl20@andrew.cmu.edu; bmcgill@colchesterconsultinggroup.com; sahmad@humana.com; ssinkula@humana.com; beshears@stanford.edu; james.choi@yale.edu; jkolstad@wharton.upenn.edu; Dlaibson@harvard.edu; brigitte_madrian@harvard.edu; jlist@uchicago.edu RI Choi, James/D-4706-2012 NR 29 TC 27 Z9 27 U1 2 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 EI 1879-1646 J9 J HEALTH ECON JI J. Health Econ. PD SEP PY 2013 VL 32 IS 5 BP 850 EP 862 DI 10.1016/j.jhealeco.2013.04.004 PG 13 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 239YD UT WOS:000326061000008 PM 23872676 ER PT J AU Chordas, C Manley, P Modest, AM Chen, B Liptak, C Recklitis, CJ AF Chordas, Christine Manley, Peter Modest, Anna Merport Chen, Bing Liptak, Cori Recklitis, Christopher J. TI Screening for Pain in Pediatric Brain Tumor Survivors Using the Pain Thermometer SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING LA English DT Article DE brain tumor; survivors; pain; screening ID QUALITY-OF-LIFE; CHILDHOOD-CANCER SURVIVOR; VISUAL ANALOG THERMOMETER; 5TH VITAL SIGN; PSYCHOMETRIC PROPERTIES; TESTICULAR CANCER; CLINICAL-TRIALS; ADULT SURVIVORS; SELF-REPORT; CHILDREN AB Numerous instruments have been developed to measure pain within various populations; however, there remains limited understanding of how these tools are applicable to childhood cancer survivors. This study compared a single-item screening measure, the Pain Thermometer (PT), with a more in-depth measure, the Brief Pain Survey (BPS), in a cohort of childhood brain tumor survivors. Ninety-nine survivors (aged 13-32 years) with a median time from diagnosis of 9.9 years (range = 2-18 years) completed the 2 instruments. Thirty-seven survivors (37.4%) were identified on the BPS as having clinically significant pain, but the PT was not found to be an accurate tool for identifying these pain cases. Application of receiver operating characteristic curve analysis of PT ratings against BPS criterion indicated overall concordance between measures. No cutoff score on the PT were identified that resulted in acceptable sensitivity, meaning pain cases identified on the BPS would be missed on the PT. Findings suggest that a multi-item screening measure may better identify clinically significant pain in childhood brain tumor survivors compared with a 1-item screening measure alone. C1 [Chordas, Christine; Manley, Peter; Modest, Anna Merport; Chen, Bing; Liptak, Cori] Dana Farber Canc Inst, Boston, MA 02115 USA. [Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. RP Chordas, C (reprint author), Dana Farber Childrens Hosp, Ctr Canc, Stop & Shop Family Pediat Neurooncol Outcomes Pro, 450 Brookline Ave, Boston, MA 02115 USA. EM christine_chordas@dfci.harvard.edu NR 76 TC 2 Z9 2 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1043-4542 EI 1532-8457 J9 J PEDIATR ONCOL NURS JI J. Pediatr. Oncol. Nurs. PD SEP PY 2013 VL 30 IS 5 BP 249 EP 259 DI 10.1177/1043454213493507 PG 11 WC Oncology; Nursing SC Oncology; Nursing GA 229IV UT WOS:000325257100003 PM 23867966 ER PT J AU Bandopadhayay, P Jabbour, A Riffkin, C Salmanidis, M Gordon, L Popovski, D Rigby, L Ashley, D Watkins, D Watkins, D Thomas, D Algar, E Ekert, P AF Bandopadhayay, P. Jabbour, A. Riffkin, C. Salmanidis, M. Gordon, L. Popovski, D. Rigby, L. Ashley, D. Watkins, D. Watkins, D. Thomas, D. Algar, E. Ekert, P. TI THE ONCOGENIC PROPERTIES OF THE EWS/WT1 FUSION PROTEIN OF DESMOPLASTIC SMALL ROUND CELL TUMOUR SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bandopadhayay, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jabbour, A.; Riffkin, C.; Salmanidis, M.; Ekert, P.] Walter Eliza Hall Inst Med Res, Melbourne, Vic, Australia. [Gordon, L.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Popovski, D.; Rigby, L.] Murdoch Childrens Res Inst, Childrens Canc Ctr, Melbourne, Vic, Australia. [Ashley, D.] Barwon Hlth, Andrew Love Canc Ctr, Melbourne, Vic, Australia. [Watkins, D.; Watkins, D.; Ekert, P.] Monash Univ, Monash Inst Med Res, Melbourne, Vic 3004, Australia. [Thomas, D.] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic, Australia. RI Gordon, Lavinia/L-1310-2016 OI Gordon, Lavinia/0000-0003-3469-8489 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 8 EP 8 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500026 ER PT J AU Moskowitz, CS Chou, JF Wolden, SL Malhotra, J Friedman, DN Mubdi, NZ Henderson, TO Leisenring, WM Stovall, M Hammond, S Hudson, MM Diller, LR Bhatia, S Neglia, JP Begg, CB Robison, LL Oeffinger, KC AF Moskowitz, C. S. Chou, J. F. Wolden, S. L. Malhotra, J. Friedman, D. N. Mubdi, N. Z. Henderson, T. O. Leisenring, W. M. Stovall, M. Hammond, S. Hudson, M. M. Diller, L. R. Bhatia, S. Neglia, J. P. Begg, C. B. Robison, L. L. Oeffinger, K. C. TI LOWER DOSES OF CHEST RADIATION TO LARGE FIELDS MAY INCREASE BREAST CANCER RISK AMONG FEMALE CANCER SURVIVORS: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Moskowitz, C. S.; Chou, J. F.; Begg, C. B.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Wolden, S. L.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Malhotra, J.] Mt Sinai Med Ctr, Dept Hematol & Oncol, New York, NY 10029 USA. [Friedman, D. N.; Oeffinger, K. C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Mubdi, N. Z.; Oeffinger, K. C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Henderson, T. O.] Univ Chicago, Dept Pediat, Med Comer Childrens Hosp, Chicago, IL 60637 USA. [Leisenring, W. M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Stovall, M.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Hammond, S.] Nationwide Childrens Hosp, Dept Lab Med, Columbus, OH USA. [Hudson, M. M.] St Jude Childrens Res Hosp, Dept Oncol Epidemiol & Canc Control, Memphis, TN 38105 USA. [Hudson, M. M.] St Jude Childrens Res Hosp, Dept Psychol, Memphis, TN 38105 USA. [Diller, L. R.] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Bhatia, S.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Neglia, J. P.] Univ Minnesota, Dept Pediat, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Robison, L. L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 12 EP 13 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500043 ER PT J AU Kieran, M Yao, X Macy, M Geyer, R Cohen, K MacDonald, T Allen, J Boklan, J Smith, A Nazemi, K Gore, L Trippett, T DiRenzo, J Narendran, A Perentesis, J Prabhu, S Pinches, N Robison, N Manley, P Chi, S AF Kieran, M. Yao, X. Macy, M. Geyer, R. Cohen, K. MacDonald, T. Allen, J. Boklan, J. Smith, A. Nazemi, K. Gore, L. Trippett, T. DiRenzo, J. Narendran, A. Perentesis, J. Prabhu, S. Pinches, N. Robison, N. Manley, P. Chi, S. TI A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA. A POETIC CONSORTIUM TRIAL SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kieran, M.; Yao, X.; Pinches, N.; Robison, N.; Manley, P.; Chi, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Macy, M.; Gore, L.] Childrens Hosp Colorado, Aurora, CO USA. [Geyer, R.] Seattle Childrens Hosp, Seattle, WA USA. [Cohen, K.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [MacDonald, T.] Childrens Healthcare Atlanta, Pediat Oncol, Atlanta, GA USA. [Allen, J.] NYU, New York, NY USA. [Boklan, J.] Phoenix Childrens Hosp, Phoenix, AZ USA. [Smith, A.] MD Anderson Canc Ctr Orlando, Orlando, FL USA. [Trippett, T.; DiRenzo, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Narendran, A.] Alberta Childrens Prov Gen Hosp, Calgary, AB T2T 5C7, Canada. [Perentesis, J.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Prabhu, S.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 19 EP 20 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500069 ER PT J AU Bergthold, G Rich, B Bandopadhayay, P Chan, J Santagata, S Hoshida, Y Golub, T Tabak, B Ferrer-Luna, R Grill, J Wen, PY Stiles, C Kieran, M Ligon, K Beroukhim, R AF Bergthold, G. Rich, B. Bandopadhayay, P. Chan, J. Santagata, S. Hoshida, Y. Golub, T. Tabak, B. Ferrer-Luna, R. Grill, J. Wen, P. Yung Stiles, C. Kieran, M. Ligon, K. Beroukhim, R. TI GENE EXPRESSION ANALYSIS OF 163 PEDIATRIC LOW-GRADE GLIOMAS REVEALS THEIR MOLECULAR HETEROGENEITY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bergthold, G.; Rich, B.; Bandopadhayay, P.; Tabak, B.; Ferrer-Luna, R.; Stiles, C.; Kieran, M.; Beroukhim, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chan, J.; Santagata, S.; Wen, P. Yung] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hoshida, Y.; Golub, T.] Broad Inst Harvard & MIT, Canc Program, Cambridge, England. [Grill, J.] Inst Gustave Roussy, Villejuif, France. [Ligon, K.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Ligon, K.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 20 EP 20 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500070 ER PT J AU Blackmon, J Chang, G Roman, A Recklitis, C AF Blackmon, J. Chang, G. Roman, A. Recklitis, C. TI TELEPHONE AUTOMATED COMPUTER ASSISTED SELF INTERVIEWS (TACASIS) TO ASSESS PSYCHOSOCIAL OUTCOMES OF PEDIATRIC CANCER SURVIVORS: ASSESSING USABILITY AND SURVIVOR PREFERENCE SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Blackmon, J.; Recklitis, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chang, G.] VA Boston Healthcare Syst, Psychiat, Brockton, MA USA. [Roman, A.] Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 6 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 22 EP 22 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500078 ER PT J AU Marcus, K Kim, H Lehmann, L Brennan, L Guinan, E AF Marcus, K. Kim, H. Lehmann, L. Brennan, L. Guinan, E. TI THE EFFECT OF EXTRAMEDULLARY DISEASE ON OUTCOME FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANT IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Marcus, K.] Boston Childrens Hosp, Boston, MA USA. [Kim, H.; Lehmann, L.; Brennan, L.; Guinan, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 28 EP 29 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500105 ER PT J AU Bandopadhayay, P Nguyen, B Masoud, S Vue, N Gholamin, S Yu, F Schubert, S Bergthold, G Mitra, S Cheshire, S Qi, J Bradner, JE Kieran, MW Beroukhim, R Cho, YJ AF Bandopadhayay, P. Nguyen, B. Masoud, S. Vue, N. Gholamin, S. Yu, F. Schubert, S. Bergthold, G. Mitra, S. Cheshire, S. Qi, J. Bradner, J. E. Kieran, M. W. Beroukhim, R. Cho, Y. J. TI BET BROMODOMAIN INHIBITION OF MYC-AMPLIFIED MEDULLOBLASTOMA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bandopadhayay, P.; Bergthold, G.; Kieran, M. W.; Beroukhim, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, B.; Masoud, S.; Vue, N.; Gholamin, S.; Yu, F.; Schubert, S.; Mitra, S.; Cheshire, S.; Cho, Y. J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Nguyen, B.; Masoud, S.; Vue, N.; Gholamin, S.; Yu, F.; Schubert, S.; Mitra, S.; Cheshire, S.; Cho, Y. J.] Stanford Univ, Lucile Packard Childrens Hosp, Stanford, CA 94305 USA. [Qi, J.; Bradner, J. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 36 EP 36 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500132 ER PT J AU Acord, M Chaudry, G Shaikh, R AF Acord, M. Chaudry, G. Shaikh, R. TI PEDIATRIC SOFT TISSUE TUMORS: DETERMINISTIC FACTORS FOR SAFETY AND ACCURACY OF DIAGNOSTIC YIELD IN IMAGE-GUIDED PERCUTANEOUS CORE-NEEDLE BIOPSIES SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Acord, M.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Chaudry, G.; Shaikh, R.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 96 EP 97 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500395 ER PT J AU Rodrigues, M Silva, R Friedrich-Medina, P Frazier, L Ribeiro, R Ribeiro, K Rodriguez-Galindo, C AF Rodrigues, M. Silva, R. Friedrich-Medina, P. Frazier, L. Ribeiro, R. Ribeiro, K. Rodriguez-Galindo, C. TI DESCRIPTIVE EPIDEMIOLOGY OF ADRENOCORTICAL CARCINOMA IN THE UNITED STATES: INCIDENCE, OUTCOME, AND RISK OF SECOND MALIGNANT NEOPLASMS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Rodrigues, M.; Silva, R.; Ribeiro, K.] Fac Ciencias Med Santa Casa, Sao Paulo, Brazil. [Friedrich-Medina, P.; Frazier, L.; Rodriguez-Galindo, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ribeiro, R.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 105 EP 105 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735500431 ER PT J AU Slavc, I Peyrl, A Chocholous, M Kieran, MW Azizi, AA Czech, T Dieckmann, K Haberler, C AF Slavc, I. Peyrl, A. Chocholous, M. Kieran, M. W. Azizi, A. A. Czech, T. Dieckmann, K. Haberler, C. TI IMPROVED SURVIVAL OF PATIENTS WITH RECURRENT MEDULLOBLASTOMA TREATED WITH A METRONOMIC AND TARGETED ANTI-ANGIOGENESIS THERAPY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Slavc, I.; Peyrl, A.; Chocholous, M.; Azizi, A. A.; Czech, T.; Dieckmann, K.] Med Univ Vienna, Vienna, Austria. [Kieran, M. W.] Dana Faber Canc Inst, Boston, MA USA. [Kieran, M. W.] Childrens Hosp, Boston, MA 02115 USA. [Haberler, C.] Med Univ Vienna, Inst Neurol, Vienna, Austria. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 132 EP 132 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735501018 ER PT J AU Bandopadhayay, P Silvera, VM Ciarlini, P La Madrid, AM Bergthold, G Ullrich, N Scott, RM Marcus, KJ Robison, N Manley, PE Chi, S Ligon, KL Goumnerova, LC Kieran, M AF Bandopadhayay, P. Silvera, V. M. Ciarlini, P. La Madrid, A. Morales Bergthold, G. Ullrich, N. Scott, R. M. Marcus, K. J. Robison, N. Manley, P. E. Chi, S. Ligon, K. L. Goumnerova, L. C. Kieran, M. TI PEDIATRIC MYXOPAPILLARY EPENDYMOMA IS ASSOCIATED WITH A SIGNIFICANT INCIDENCE OF DISSEMINATED OR RECURRENT DISEASE BUT AN EXCELLENT OVERALL SURVIVAL. SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bandopadhayay, P.; La Madrid, A. Morales; Bergthold, G.; Robison, N.; Manley, P. E.; Chi, S.; Kieran, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Silvera, V. M.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [Ciarlini, P.; Ligon, K. L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Ullrich, N.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Scott, R. M.; Goumnerova, L. C.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Marcus, K. J.] Boston Childrens Hosp, Dept Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 136 EP 136 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735501037 ER PT J AU Bandopadhayay, P Bergthold, G Goumnerova, L La Madrid, AM Chi, S Ullrich, N Robison, N Marcus, K Beroukhim, R Kieran, M Manley, P AF Bandopadhayay, P. Bergthold, G. Goumnerova, L. La Madrid, A. Morales Chi, S. Ullrich, N. Robison, N. Marcus, K. Beroukhim, R. Kieran, M. Manley, P. TI LONG-TERM OUTCOME OF 3945 CHILDREN DIAGNOSED WITH PEDIATRIC LOW-GRADE GLIOMAS: AN ANALYSIS OF THE SURVEILLANCE EPIDEMIOLOGY AND END RESULTS (SEER) DATABASE SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bandopadhayay, P.; Bergthold, G.; La Madrid, A. Morales; Chi, S.; Robison, N.; Marcus, K.; Beroukhim, R.; Kieran, M.; Manley, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goumnerova, L.; Ullrich, N.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2013 VL 60 SU 3 BP 136 EP 136 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 222MP UT WOS:000324735501035 ER PT J AU Spencer, JK AF Spencer, Jacqueline K. TI A Variation on the Patient-Centered Medical Home: Transforming Primary Care within the Veteran's Health Administration SO PUBLIC ADMINISTRATION REVIEW LA English DT Editorial Material C1 VA Boston Healthcare Syst, Primary & Ambulatory Care, Boston, MA USA. RP Spencer, JK (reprint author), VA Boston Healthcare Syst, Primary & Ambulatory Care, Boston, MA USA. EM jacqueline.spencer3@va.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0033-3352 EI 1540-6210 J9 PUBLIC ADMIN REV JI Public Adm. Rev. PD SEP PY 2013 VL 73 SU 1 SI SI BP S92 EP S93 DI 10.1111/puar.12126 PG 2 WC Public Administration SC Public Administration GA 217VY UT WOS:000324391800012 ER PT J AU Yadav, P De Castro, DK Waner, M Meyer, L Fay, A AF Yadav, Prashant De Castro, Dawn K. Waner, Milton Meyer, Lutz Fay, Aaron TI Vascular Anomalies of the Head and Neck: A Review of Genetics SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE Arteriovenous malformation; hemangioma; inheritance; lymphatic malformation; port wine stain; venous malformation ID PORT-WINE STAIN; VENOUS MALFORMATIONS; INFANTILE HEMANGIOMA; RASA1 MUTATIONS; ARTERIOVENOUS-MALFORMATIONS; CAPILLARY MALFORMATION; NUCHAL TRANSLUCENCY; TYROSINE KINASE; TURNER SYNDROME; CHROMOSOME AB Purpose: Vascular anomalies comprise malformations, hemangiomas, and rare tumors. The commonality among these lesions is their origin in vascular endothelia. Most occur sporadically, but occasional inheritance is observed and thus allows genetic research and insight into etiology. This review highlights those vascular anomalies in which genetic inheritance has been demonstrated. Methods: A comprehensive literature search was performed on PubMed. Fifty-five full-length articles were reviewed. Results: Five categories of vascular anomalies with patterned inheritance were identified: arteriovenous malformation (AVM), capillary malformation (CM), lymphatic malformation (LM), venous malformation (VM), and infantile hemangioma (IH). Capillary and arteriovenous malformation subtypes are associated with a RASA-1 gene mutation and show autosomal dominant inheritance. VEGFR3 mutations have been associated with generalized forms of LM and lymphedema. Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance. Familial clustering and atopic disease are associated with infantile hemangioma, and gene expression varies with the developmental stage of these lesions. Conclusion: Most vascular anomalies occur sporadically, but several genes and genetic disorders have been associated with them. Specific forms of capillary malformation appear to be most convincingly associated with genomic errors. Further research promises new insights into the development of this diverse group of disorders. C1 [Yadav, Prashant; De Castro, Dawn K.; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Yadav, Prashant; De Castro, Dawn K.; Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Waner, Milton] Lenox Hill Hosp, Vasc Birthmark Inst New York, New York, NY 10021 USA. [Meyer, Lutz] St Joseph Hosp, Ctr Vasc Malformat Children, Berlin, Germany. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu NR 53 TC 5 Z9 7 U1 0 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 257 EP 266 DI 10.3109/08820538.2013.825279 PG 10 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800001 PM 24010650 ER PT J AU Lee, NG Kim, LA Freitag, SK AF Lee, Nahyoung Grace Kim, Leo A. Freitag, Suzanne K. TI The Role of Genetics in the Pathogenesis of Periocular Cutaneous Neoplasms: Implications for Targeted Therapy SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Cancer; eyelid; genetics; targeted; therapies ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; MUIR-TORRE SYNDROME; PHASE-II; MOLECULAR PATHOGENESIS; METASTATIC MELANOMA; NEVUS SYNDROME; SKIN-CANCER; SIGNALING PATHWAY; HEDGEHOG PATHWAY AB In the past, cutaneous malignancies of the periocular region were primarily treated surgically with few other options. As the genetic bases of these tumors have become elucidated, targeted therapies aimed specifically at pathways that are felt to be responsible for cellular proliferation and uncontrolled growth have emerged with new promise. This review contains a summary of the various genetic implications of cutaneous neoplasms as well as their corresponding targeted systemic therapies. C1 [Lee, Nahyoung Grace; Kim, Leo A.; Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Lee, NG (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Grace_Lee@meei.harvard.edu FU NEI NIH HHS [K12 EY016335] NR 57 TC 0 Z9 0 U1 1 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 267 EP 274 DI 10.3109/08820538.2013.825278 PG 8 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800002 PM 24138034 ER PT J AU Chang, HYP Chodosh, J AF Chang, Han-Ying Peggy Chodosh, James TI The Genetics of Keratoconus SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Genetics; keratoconus ID AUTOSOMAL-DOMINANT KERATOCONUS; LEBER CONGENITAL AMAUROSIS; MITRAL-VALVE-PROLAPSE; DOWN-SYNDROME; ANTERIOR KERATOCONUS; FAMILIAL KERATOCONUS; CORNEAL TOPOGRAPHY; MONOZYGOTIC TWINS; CANDIDATE GENE; LYSYL OXIDASE AB Keratoconus is a bilateral, non-inflammatory corneal ectasia characterized by progressive conical thinning and protrusion of the cornea. Its etiology has long been believed to be multifactorial, with environmental, behavioral, and genetic factors all contributing to the disease process. This review focuses specifically on examining the evidence that supports a genetic basis for keratoconus. C1 [Chang, Han-Ying Peggy; Chodosh, James] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM James_Chodosh@meei.harvard.edu NR 98 TC 6 Z9 6 U1 0 U2 9 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 275 EP 280 DI 10.3109/08820538.2013.825295 PG 6 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800003 PM 24138035 ER PT J AU Hamill, CE Schmedt, T Jurkunas, U AF Hamill, Cecily E. Schmedt, Thore Jurkunas, Ula TI Fuchs Endothelial Cornea Dystrophy: A Review of the Genetics Behind Disease Development SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE cornea; Fuchs dystrophy; endothelium; genetics; penetrating keratoplasty ID PENETRATING KERATOPLASTY; IC3D CLASSIFICATION; MISSENSE MUTATIONS; CELL-DEVELOPMENT; VIII COLLAGEN; UNITED-STATES; RISK-FACTORS; LOCUS; PROTEINS; E2-2 AB Fuchs dystrophy represents the most common form of endothelial dystrophy and is a significant cause of visual impairment. The cause of Fuchs dystrophy is a complicated combination of both genetic and environmental factors. Understanding the underlying causes of the disease can potentially lead to new medical treatments preventing loss of vision. C1 [Hamill, Cecily E.; Schmedt, Thore; Jurkunas, Ula] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Hamill, CE (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM cecily_hamill@meei.harvard.edu FU NEI NIH HHS [R01 EY020581] NR 50 TC 6 Z9 6 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 281 EP 286 DI 10.3109/08820538.2013.825283 PG 6 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800004 PM 24138036 ER PT J AU Qazi, Y Hamrah, P AF Qazi, Yureeda Hamrah, Pedram TI Gene Therapy in Corneal Transplantation SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Alternative splicing; angiogenesis; graft survival; immunomodulation; keratoplasty; nanotechnology ID HIGH-RISK KERATOPLASTY; COMPACTED DNA-NANOPARTICLES; RECOMBINANT ADENOASSOCIATED VIRUS; HIGH-EFFICIENCY TRANSDUCTION; RANDOMIZED CONTROLLED-TRIAL; RETINAL-PIGMENT EPITHELIUM; INDUCED IMMUNE DEVIATION; PROMOTES GRAFT-SURVIVAL; T MONOCLONAL-ANTIBODIES; TOPICAL CYCLOSPORINE-A AB Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection. C1 [Qazi, Yureeda; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea & Refract Surg Serv, Boston, MA 02114 USA. [Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP Hamrah, P (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu FU NEI NIH HHS [K08 EY020575, L30 EY021919] NR 192 TC 3 Z9 3 U1 0 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 287 EP 300 DI 10.3109/08820538.2013.825297 PG 14 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800005 PM 24138037 ER PT J AU Ojha, P Wiggs, JL Pasquale, LR AF Ojha, Pallavi Wiggs, Janey L. Pasquale, Louis R. TI The Genetics of Intraocular Pressure SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Genetics; glaucoma; intraocular pressure; risk factors ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; TO-DISC RATIO; CENTRAL CORNEAL THICKNESS; BEAVER-DAM EYE; RISK-FACTORS; CIGARETTE-SMOKING; HERITABILITY; POPULATION; MYOCILIN AB Glaucoma is a leading cause of irreversible blindness. Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, yet there is little known about the molecular events that regulate IOP. Genetic and genomic studies have helped identify genes that influence IOP and could lead to the identification of biological pathways that serve as targets for novel pressure-modifying therapies. Genetic linkage studies resulted in the identification of several genes that cause Mendelian (autosomal dominant or autosomal recessive) forms of high-pressure glaucoma, including MYOC, PITX2, FOXC1, and CYP1B1. Classical twin studies suggest that IOP is a heritable trait. More recently, genome-wide association studies (GWAS) have shown that common genetic variants in the GAS7 and TMCO1 genomic regions are associated with elevated IOP. TMCO1 has also been associated with primary open-angle glaucoma in patients with advanced disease. A further study identifying additional genes contributing to IOP will be necessary to fully define the underlying genetic architecture of IOP. C1 [Ojha, Pallavi; Wiggs, Janey L.; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Pasquale, Louis R.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. RP Ojha, P (reprint author), 2 Hawthorne Pl,Apt 2C, Boston, MA 02114 USA. EM Pallavi_Ojha@meei.harvard.edu NR 46 TC 5 Z9 6 U1 0 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 301 EP 305 DI 10.3109/08820538.2013.825291 PG 5 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800006 PM 24138038 ER PT J AU Lee, HJ Colby, KA AF Lee, Hyunjoo J. Colby, Kathryn A. TI A Review of the Clinical and Genetic Aspects of Aniridia SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Aniridia; genetics; keratopathy; keratoprosthesis; PAX6 ID AUTOSOMAL-DOMINANT KERATITIS; PAX6 GENE; GILLESPIE-SYNDROME; PENETRATING KERATOPLASTY; BOSTON KERATOPROSTHESIS; CONGENITAL ANIRIDIA; MENTAL-RETARDATION; CEREBELLAR-ATAXIA; MUTATIONS; KERATOPATHY AB Aniridia classically presents with a bilateral congenital absence or malformation of the irides, foveal hypoplasia, and nystagmus, and patients tend to develop visually significant pre-senile cataracts and keratopathy. Additionally, they are at high risk for developing glaucoma. Classic aniridia can be genetically defined as the presence of a PAX6 gene deletion or loss-of-function mutation that results in haploinsufficiency. Variants of aniridia, which include a condition previously referred to as autosomal dominant keratitis, are likely due to PAX6 mutations that lead to partial loss of PAX6 function. Aniridia-associated keratopathy (AAK) is a progressive and potentially debilitating problem affecting aniridic patients. The current treatments for AAK are to replace the limbal stem cells through keratolimbal allograft (KLAL) with or without subsequent keratoplasty for visual rehabilitation, or to implant a Boston type 1 keratoprosthesis. Future therapies for AAK may be aimed at the genetic modification of corneal limbal stem cells. C1 [Lee, Hyunjoo J.; Colby, Kathryn A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Colby, KA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Kathryn_Colby@MEEI.Harvard.edu NR 37 TC 9 Z9 9 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 306 EP 312 DI 10.3109/08820538.2013.825293 PG 7 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800007 PM 24138039 ER PT J AU Mansouri, B Stacy, RC Kruger, J Cestari, DM AF Mansouri, Behzad Stacy, Rebecca C. Kruger, Joshua Cestari, Dean M. TI Deprivation Amblyopia and Congenital Hereditary Cataract SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Amblyopia; cataract; congenital; deprivation; genetic; hereditary ID BILATERAL VISUAL IMPAIRMENT; QUALITY-OF-LIFE; CHILDREN AGED 7; RANDOMIZED-TRIAL; MISSENSE MUTATION; ANISOMETROPIC AMBLYOPIA; VISUOMOTOR BEHAVIOR; PEDIATRIC CATARACT; MODERATE AMBLYOPIA; GENE DOSAGE AB Amblyopia is a neurodevelopmental disorder of vision associated with decreased visual acuity, poor or absent stereopsis, and suppression of information from one eye.(1,2) Amblyopia may be caused by strabismus (strabismic amblyopia), refractive error (anisometropic amblyopia), or deprivation from obstructed vision (deprivation amblyopia).(1) In the developed world, amblyopia is the most common cause of childhood visual impairment,(3) which reduces quality of life(4) and also almost doubles the lifetime risk of legal blindness.(5,6) Successful treatment of amblyopia greatly depends on early detection and treatment of predisposing disorders such as congenital cataract, which is the most common cause of deprivational amblyopia. Understanding the genetic causes of congenital cataract leads to more effective screening tests, early detection and treatment of infants and children who are at high risk for hereditary congenital cataract. C1 [Mansouri, Behzad; Stacy, Rebecca C.; Kruger, Joshua; Cestari, Dean M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Mansouri, Behzad] Univ Manitoba, Dept Internal Med, Neurol Sect, Winnipeg, MB, Canada. RP Cestari, DM (reprint author), Massachusetts Eye & Ear Infirm Neuro Ophthalmol, 9th Floor,243 Charles St, Boston, MA 02114 USA. EM dean_cestari@meei.harvard.edu NR 79 TC 3 Z9 3 U1 2 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 321 EP 326 DI 10.3109/08820538.2013.825289 PG 6 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800009 PM 24138041 ER PT J AU Pillai, P Sobrin, L AF Pillai, Parvathy Sobrin, Lucia TI Blau Syndrome-Associated Uveitis and the NOD2 Gene SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Blau syndrome; NOD2; pediatric uveitis ID PEDIATRIC GRANULOMATOUS ARTHRITIS; EARLY-ONSET SARCOIDOSIS; CARD15 MUTATIONS; CROHNS-DISEASE; SYSTEMIC GRANULOMATOSIS; KAPPA-B; NOD2/CARD15; SUSCEPTIBILITY; ACTIVATION; PHENOTYPE AB Blau syndrome (BS), a rare autosomal dominant autoinflammatory syndrome, is an example of a monogenic disease. It was first described as a classic triad of uveitis, arthritis, and exanthema, typically seen in patients less than four years of age. Since that time, the phenotype has been expanded to include fever, cranial neuropathies, cardiovascular abnormalities, and granulomas of the liver and kidney. The ocular inflammation is often a panuveitis that occurs later in the disease course and typically carries the greatest morbidity in BS. BS has been mapped to the chromosomal region 16q12-21, also known as the NOD2 gene (formerly CARD15/NOD2). The disease is secondary to a single amino acid mutation NOD2 that leads to peptidoglycan-independent activity of nuclear factor (NF)-kappa B. Clinical and genetic aspects of BS will be discussed, as well as recent advances in treatment protocols. C1 [Pillai, Parvathy; Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis Serv, Boston, MA USA. RP Sobrin, L (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM lucia_sobrin@meei.harvard.edu NR 48 TC 4 Z9 4 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 327 EP 332 DI 10.3109/08820538.2013.825285 PG 6 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800010 PM 24010719 ER PT J AU Omar, AF Silva, PS Sun, JK AF Omar, Ahmed F. Silva, Paolo S. Sun, Jennifer K. TI Genetics of Diabetic Retinopathy SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Diabetic retinopathy; eye; genetics; single nucleotide polymorphism; vascular endothelial growth factor ID ALDOSE REDUCTASE GENE; ENDOTHELIAL GROWTH-FACTOR; SOUTH INDIAN COHORT; REPEAT POLYMORPHIC MARKER; RENIN-ANGIOTENSIN SYSTEM; GLYCATION END-PRODUCTS; VEGF GENE; RISK-FACTORS; RAGE GENE; MICROVASCULAR COMPLICATIONS AB Multiple studies have shown that genetic factors may play an important role in determining an individual's risk for the development of diabetic retinopathy (DR) and progression to proliferative DR. However, consistent and definitive genetic associations with DR across broad populations have been not been established. Numerous genes have been studied for their association with DR and the results of these investigations have most specifically pointed to three specific genes that are likely involved in DR development and progression. The gene coding for vascular endothelial growth factor, aldose reductase, and the receptor for advanced glycation end products have been extensively evaluated, and specific polymorphisms of these genes have been suggested to potentially increase the risk of DR development. In this paper, we have reviewed the published literature on the genetics of DR and the potential implications for DR development and progression. C1 [Omar, Ahmed F.; Silva, Paolo S.; Sun, Jennifer K.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo S.; Sun, Jennifer K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM PaoloAntonio.Silva@joslin.harvard.edu NR 96 TC 7 Z9 7 U1 2 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 337 EP 346 DI 10.3109/08820538.2013.825287 PG 10 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800012 PM 24138043 ER PT J AU Dyer, KH Silva, PS Sun, JK AF Dyer, Kelli H. Silva, Paolo S. Sun, Jennifer K. TI Vascular Endothelial Growth Factor Gene Polymorphisms and Vitreous Proteome Changes in Diabetic Retinopathy SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE carbonic anhydrase-I (CA-I); C-634G polymorphism; kallikrein-kinin system; Rs3025021 polymorphism; Rs699947 polymorphism; single nucleotide polymorphisms (SNPs) ID MACULAR EDEMA; PERMEABILITY FACTOR; VEGF GENE; RETINAL NEOVASCULARIZATION; IRIS NEOVASCULARIZATION; PIGMENT EPITHELIUM; AQUEOUS-HUMOR; ASSOCIATION; RISK; RANIBIZUMAB AB Ischemic retinal diseases, particularly diabetic retinopathy, continue to significantly impact vision and remain a leading cause of vision loss in working-aged adults. Identifying specific genetic risk factors for ischemic-driven pathways that increase susceptibility to developing diabetic retinopathy is a priority to allow development of accurate risk assessment algorithms, employ earlier intervention, and design novel treatment strategies to reduce the associated visual complications. Single nucleotide polymorphisms (SNPs) in the VEGF gene have been shown to influence the expression of the VEGF protein. Several studies suggest that SNPs in the VEGF gene mediate genetic predisposition to diabetic retinopathy. In addition, alterations in the vitreous proteome, including carbonic anhydrase mediated vascular permeability, have been found to be associated with sight-threatening proliferative diabetic retinopathy and macular edema. Inhibition of these factors could provide new therapeutic opportunities for the treatment of diabetic retinopathy. C1 [Dyer, Kelli H.; Silva, Paolo S.; Sun, Jennifer K.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo S.; Sun, Jennifer K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Sun, JK (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM Jennifer.Sun@joslin.harvard.edu NR 46 TC 2 Z9 2 U1 2 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 347 EP 354 DI 10.3109/08820538.2013.825284 PG 8 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800013 PM 24138044 ER PT J AU Kanoff, J Miller, J AF Kanoff, Justin Miller, Joan TI Pharmacogenetics of the Treatment Response of Age-Related Macular Degeneration with Ranibizumab and Bevacizumab SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Bevacizumab; complement factor H; macular degeneration; pharmacogenetics; ranibizumab ID COMPLEMENT FACTOR-H; ENDOTHELIAL GROWTH-FACTOR; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; RANDOMIZED CLINICAL-TRIAL; PHOTODYNAMIC THERAPY; ASSOCIATION; SUSCEPTIBILITY; RISK; POLYMORPHISMS; VERTEPORFIN AB Introduction: Age-related macular degeneration is a major cause of blindness among people aged 50 and older in industrialized countries. Anti-VEGF therapy has been tremendously successful in the treatment of neovascular macular degeneration. Examining the pharmacogenetics of patients' response to the anti-VEGF molecules could allow for a tailored treatment strategy based on patients' underlying genetics rather than the "one-size fits all" approach currently used. Methods: Review of the English literature for papers examining the pharmacogenetics of treatment response of neovascular macular degeneration to either ranibizumab or bevacizumab. Polymorphisms in CFH, ARMS2, HTRA1 and VEGF A were examined and reviewed. Results: Patients with the high-risk CC genotype in complement factor H (CFH) had a worse response to therapy with ranibizumab and bevacizumab. No clear trends were found with ARMS2, HTRA1 and VEGF A. Conclusions: The goal of personalized medicine is to craft a treatment program that is ideally suited to an individual patient's disease and genetic make-up rather than simply what works for a large population who share similar disease characteristics. Continued research is needed to achieve this goal for the treatment of age-related macular degeneration. C1 [Kanoff, Justin; Miller, Joan] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Kanoff, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Justin_Kanoff@meei.harvard.edu NR 41 TC 6 Z9 6 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 355 EP 360 DI 10.3109/08820538.2013.825292 PG 6 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800014 PM 24010796 ER PT J AU Werdich, XQ Jakobiec, FA Singh, AD Kim, IK AF Werdich, Xiang Q. Jakobiec, Frederick A. Singh, Arun D. Kim, Ivana K. TI A Review of Advanced Genetic Testing for Clinical Prognostication in Uveal Melanoma SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE BAP1; cytogenetics; gene expression profile; genetic testing; metastasis; monosomy 3; prognostication; uveal melanoma ID COMPARATIVE GENOMIC HYBRIDIZATION; DEPENDENT PROBE AMPLIFICATION; IN-SITU HYBRIDIZATION; COMS RANDOMIZED TRIAL; CHOROIDAL MELANOMA; MICROSATELLITE ANALYSIS; MALIGNANT-MELANOMA; TUMOR PROGRESSION; MONOSOMY 3; IODINE-125 BRACHYTHERAPY AB Uveal melanoma (UM) has a strong propensity to metastasize and the prognosis for metastatic disease is very poor. It has been suggested that occult micrometastases are already present, but undetectable, in many patients at the time when the primary ocular tumor is diagnosed and treated. To identify high-risk patients for close monitoring and early intervention with prophylactic adjuvant systemic therapy, an accurate predictive system is necessary for stratifying those patients at risk of developing metastatic disease. To date, many clinical and histopathological features, molecular pathway characteristics, and genetic fingerprints of UM have been suggested for disease prognostication. Among the newest of them, tumor genetics has received the most attention in demonstrating promise as a prognostic tool. Because of the plethora of recent developments, we summarize and compare in this review the important standard and more advanced cytogenetic prognostic markers. We further describe the variety of genetic tests available for prognostication of UM, and provide a critical assessment of the respective advantages and disadvantages of these tools. C1 [Werdich, Xiang Q.; Jakobiec, Frederick A.; Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Singh, Arun D.] Cleveland Clin, Cole Eye Inst, Dept Ophthalm Oncol, Cleveland, OH 44106 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 95 TC 2 Z9 2 U1 0 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 361 EP 371 DI 10.3109/08820538.2013.825290 PG 11 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800015 PM 24010756 ER PT J AU Abdollahi, SH Hirose, T AF Abdollahi, Sara Haji Hirose, Tatsuo TI Stargardt-Fundus Flavimaculatus: Recent Advancements and Treatment SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE ABCA4; atp-binding cassette transporter; Fundus flavimaculatus; Juvenile macular dystrophy; Stargardt disease ID MACULAR DEGENERATION; ABCA4 MUTATIONS; DISEASE; DYSTROPHY; GENE; ACCUMULATION; PHENOTYPES; RETINA; ELOVL4; LIGHT AB Stargardt disease is the most common form of autosomal recessive macular dystrophy. Mutation in the ABCA4 gene (ABCR protein) is responsible for disease manifestation in more than 95% of Stargardt patients. ABCA4 codes for a member of the ATP binding cassette transmembrane protein involved in the transport of all-trans retinal. Dysfunction in this protein causes accumulation of lipofuscin, which is toxic to the RPE and photoreceptors. Presenting symptoms, fundus appearance, and progression of the disease are widely variable in this disease. Different imaging modalities have been utilized to study the presentation and evolution of fundus changes. Although there is ongoing research to better understand the disease process and ways to alternate its path, currently there is no treatment for Startgardt patients. C1 [Abdollahi, Sara Haji] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hirose, Tatsuo] Harvard Univ, Sch Med, Dept Opthalmol, Boston, MA USA. [Hirose, Tatsuo] Boston Eye Grp, Boston, MA USA. RP Abdollahi, SH (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Sara_haji@meei.harvard.edu NR 48 TC 4 Z9 4 U1 0 U2 8 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 372 EP 376 DI 10.3109/08820538.2013.825286 PG 5 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800016 ER PT J AU Haddad, NMN Cavallerano, JD Silva, PS AF Haddad, Nour Maya N. Cavallerano, Jerry D. Silva, Paolo S. TI Von Hippel-Lindau Disease: A Genetic and Clinical Review SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE Angiogenesis; genotype-phenotype correlation; hypoxia induced factor; optic disc hemangioblastoma; retinal hemangioblastoma; VEGF ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR PROTEIN; GENOTYPE-PHENOTYPE CORRELATION; VASCULAR-PERMEABILITY FACTOR; RECEPTOR INHIBITOR SU5416; VHL DISEASE; RETINAL HEMANGIOBLASTOMA; VISUAL FUNCTION; CANCER-THERAPY; EXPRESSION AB Background: Von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited systemic cancer syndrome that gives rise to cystic and highly vascularized tumors in many organs, including the eye. Recent studies have contributed to the understanding of VHL pathophysiology, genetics, and the role of the VHL protein. This article reviews recent studies on VHL clinical findings, genetics and tumorigenesis. Methods: Literature review of articles on VHL genetics with correlation to clinical findings. Results: Genotype-phenotype correlation studies show that patients with a complete deletion mutation of the VHL gene, relative to participants with a missense or protein-truncating mutation, had better visual acuity and decreased tumorigenesis incidence of retinal hemangioblastomas. It has also been documented that higher levels of vascular endothelial growth factor (VEGF), hypoxia induced factor (HIF), and ubiquitin are found in ocular hemangioblastomas. The stromal foamy vacuolated cells seem to be the true tumor cells of the disease acting on the surrounding endothelial cells in ocular hemangioblastomas. Tumor cells and ocular lesions have shown increased levels of Erythropoietin (Epo), Epo receptor (EpoR), and CD133. Also, CXCR4, a CXC chemokine receptor, is expressed in retinal VHL hemangioblastomas. Recent studies suggest that the VHL mutation alone may not be sufficient to develop VHL-associated neoplasms. Studies suggest that targeting various proteins along with anti-angiogenesis molecules may be a better therapeutic approach than targeting VEGF alone. Conclusion: Understanding of the mechanisms and genetics underlying VHL and its associated retinal hemangioblastomas has increased substantially in recent years. This knowledge suggests that future advances may include better identification of individuals at higher risk of vision loss and the development of novel individualized therapies. C1 [Haddad, Nour Maya N.; Cavallerano, Jerry D.; Silva, Paolo S.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Cavallerano, Jerry D.; Silva, Paolo S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Haddad, NMN (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM nour.haddad@joslin.harvard.edu NR 76 TC 10 Z9 11 U1 2 U2 19 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 377 EP 386 DI 10.3109/08820538.2013.825281 PG 10 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800017 PM 24138046 ER PT J AU Kim, DY Mukai, S AF Kim, David Y. Mukai, Shizuo TI X-linked Juvenile Retinoschisis (XLRS): A Review of Genotype-Phenotype Relationships SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE Genotype; juvenile X-linked retinischisis; phenotype; retinischisis; XLRS ID CONGENITAL RETINOSCHISIS; CLINICAL-FEATURES; MUTATIONS; GENE; EXPRESSION; FAMILY; CELLS; RS1; PHOTORECEPTOR; SPECTRUM AB X-linked juvenile retinoschisis (XLRS) is one of the most common genetic causes of juvenile progressive retinal-vitreal degeneration in males. To date, more than 196 different mutations of the RS1 gene have been associated with XLRS. The mutation spectrum is large and the phenotype variable. This review will focus on the clinical features of XLRS and examine the relationship between phenotype and genotype. C1 [Kim, David Y.; Mukai, Shizuo] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Mukai, S (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM shizuo_mukai@meei.harvard.edu NR 37 TC 3 Z9 3 U1 2 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 392 EP 396 DI 10.3109/08820538.2013.825299 PG 5 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800019 PM 24138048 ER PT J AU Ehrenberg, M Pierce, EA Cox, GF Fulton, AB AF Ehrenberg, Miriam Pierce, Eric A. Cox, Gerald F. Fulton, Anne B. TI CRB1: One Gene, Many Phenotypes SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Coats disease; early onset rod-cone dystrophy (EORCD); inherited retinal dystrophy (IRD); Leber congenital amaurosis (LCA); preserved para-arteriolar retinal pigment epithelium (PPRPE); retinitis pigmentosa (RP) ID LEBER CONGENITAL AMAUROSIS; INHERITED RETINAL DYSTROPHIES; DOMINANT RETINITIS-PIGMENTOSA; MOUSE MODEL; CRUMBS HOMOLOG-1; PHOTORECEPTOR DEGENERATION; EXUDATIVE VASCULOPATHY; GENOTYPING MICROARRAY; DROSOPHILA-CRUMBS; MODIFIER ALLELES AB Mutations in the CRB1 gene cause severe retinal degenerations, which may present as Leber congenital amaurosis, early onset retinal dystrophy, retinitis pigmentosa, or cone-rod dystrophy. Some clinical features should alert the ophthalmologist to the possibility of CRB1 disease. These features are nummular pigmentation of the retina, atrophic macula, retinal degeneration associated with Coats disease, and a unique form of retinitis pigmentosa named para-arteriolar preservation of the retinal pigment epithelium (PPRPE). Retinal degenerations associated with nanophthalmos and hyperopia, or with keratoconus, can serve as further clinical cues to mutations in CRB1. Despite this, no clear genotype-phenotype relationship has been established in CRB1 disease. In CRB1-disease, as in other inherited retinal degenerations (IRDs), it is essential to diagnose the specific disease-causing gene for the disease as genetic therapy has progressed considerably in the last few years and might be applicable. C1 [Ehrenberg, Miriam; Fulton, Anne B.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, Boston, MA 02115 USA. [Ehrenberg, Miriam; Pierce, Eric A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,ERG Serv, Boston, MA 02115 USA. [Cox, Gerald F.] Boston Childrens Hosp, Div Genet, Boston, MA USA. [Cox, Gerald F.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Cox, Gerald F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cox, Gerald F.] Genzyme, Clin Dev, Cambridge, MA USA. RP Ehrenberg, M (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM miriberg@gmail.com OI Pierce, Eric/0000-0002-2354-4102 NR 72 TC 3 Z9 3 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 397 EP 405 DI 10.3109/08820538.2013.825277 PG 9 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800020 PM 24138049 ER PT J AU Ramsey, DJ Ramsey, KM Vavvas, DG AF Ramsey, David J. Ramsey, Kathryn Moynihan Vavvas, Demetrios G. TI Genetic Advances in Ophthalmology: The Role of Melanopsin-Expressing, Intrinsically Photosensitive Retinal Ganglion Cells in the Circadian Organization of the Visual System SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Circadian photoentrainment; intrinsically photosensitive retinal ganglion cells; melanopsin (OPN4); retina; molecular clock ID SEASONAL AFFECTIVE-DISORDER; HEREDITARY OPTIC NEUROPATHY; RHYTHM SLEEP DISORDERS; MOUSE RETINA; MAMMALIAN RETINA; LIGHT RESPONSE; SUPRACHIASMATIC NUCLEUS; INTRAOCULAR-PRESSURE; MESSENGER-RNA; BRIGHT LIGHT AB Daily changes in the light-dark cycle are the principal environmental signal that enables organisms to synchronize their internal biology with the 24-hour day-night cycle. In humans, the visual system is integral to photoentrainment and is primarily driven by a specialized class of intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin (OPN4) in the inner retina. These cells project through the retinohypothalamic tract (RHT) to the suprachiasmatic nuclei (SCN) of the hypothalamus, which serves as the body's master biological clock. At the same time, the retina itself possesses intrinsic circadian oscillations, exemplified by diurnal fluctuations in visual sensitivity, neurotransmitter levels, and outer segment turnover rates. Recently, it has been noted that both central and peripheral oscillators share a molecular clock consisting of an endogenous, circadian-driven, transcription-translation feedback loop that cycles with a periodicity of approximately 24 hours. This review will cover the role that melanopsin and ipRGCs play in the circadian organization of the visual system. C1 [Ramsey, David J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02114 USA. [Ramsey, David J.; Vavvas, Demetrios G.] Mass Gen Hosp, Boston, MA USA. [Ramsey, Kathryn Moynihan] Northwestren Univ Feinberg, Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL USA. [Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 177 TC 4 Z9 4 U1 1 U2 15 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 406 EP 421 DI 10.3109/08820538.2013.825294 PG 16 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800021 PM 24010846 ER PT J AU Skidd, PM Lessell, S Cestari, DM AF Skidd, P. M. Lessell, S. Cestari, D. M. TI Autosomal Dominant Hereditary Optic Neuropathy (ADOA): A Review of the Genetics and Clinical Manifestations of ADOA and ADOA SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Autosomal dominant hereditary optic atrophy plus; genetics; Kjer's syndrome; neuro-ophthalmology; OPA1 ID OPA1 MUTATIONS; MISSENSE MUTATION; ATROPHY; DISORDER; PATHOPHYSIOLOGY; OPHTHALMOPLEGIA; PENETRANCE; SPECTRUM AB Autosomal dominant hereditary optic atrophy (ADOA), also known as Kjer's syndrome, is a common hereditary cause of progressive bilateral vision loss. Recent advancements in the understanding of the genetics of this condition have revealed that a single gene may account for a large portion of the clinical manifestations in these patients. It has long been recognized that in a not-insignificant number of ADOA patients, a number of "plus" symptoms may follow decades after vision loss. It is important that clinicians recognize the potential link to "plus" manifestations. The goal of this manuscript is to provide for the general ophthalmologist a practical outline of the genetics and clinical manifestations of ADOA and the ADOA+. C1 [Skidd, P. M.; Lessell, S.; Cestari, D. M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Skidd, PM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM philskidd@hotmail.com NR 29 TC 4 Z9 4 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 422 EP 426 DI 10.3109/08820538.2013.825296 PG 5 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800022 PM 24138050 ER PT J AU Kruger, JM Mansouri, B Cestari, DM AF Kruger, Joshua M. Mansouri, Behzad Cestari, Dean M. TI An Update on the Genetics of Comitant Strabismus SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Genetics; strabismus; STBMS1 ID SUSCEPTIBILITY LOCUS; EXPRESSION; ORIGIN AB Genetics play a significant role in the development of comitant strabismus and elucidating the relevant mechanisms that cause it may lead to the development of new therapeutic options. The genetics of strabismus are complex and involve the interactions of multiple genes. This article reviews the progress that has been made in the understanding of the genetic causes of comitant strabismus including linkage studies that have identified a variety of candidate sites, RNA and protein studies that have identified genes with altered regulation, and a study that establishes a role for genetic imprinting in comitant strabismus. C1 [Kruger, Joshua M.; Mansouri, Behzad; Cestari, Dean M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Neuro Ophthalmol Serv, Boston, MA 02114 USA. RP Cestari, DM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Neuro Ophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. EM Dean_Cestari@meei.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PD SEP-NOV PY 2013 VL 28 IS 5-6 BP 438 EP 441 DI 10.3109/08820538.2013.825298 PG 4 WC Ophthalmology SC Ophthalmology GA 239QP UT WOS:000326040800024 PM 24138052 ER PT J AU Ganguly, K Byl, NN Abrams, GM AF Ganguly, Karunesh Byl, Nancy N. Abrams, Gary M. TI Neurorehabilitation: Motor Recovery After Stroke as an Example SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; INDUCED MOVEMENT THERAPY; UPPER-LIMB RECOVERY; SPINAL-CORD-INJURY; FUNCTIONAL RECOVERY; BRAIN-STIMULATION; ISCHEMIC-STROKE; CORTICAL STIMULATION; CONTROLLED-TRIAL; CLINICAL-TRIALS AB The field of neurorehabilitation aims to translate neuroscience research toward the goal of maximizing functional recovery after neurological injury. A growing body of research indicates that the fundamental principles of neurological rehabilitation are applicable to a broad range of congenital, degenerative, and acquired neurological disorders. In this perspective, we will focus on motor recovery after acquired brain injuries such as stroke. Over the past few decades, a large body of basic and clinical research has created an experimental and theoretical foundation for approaches to neurorehabilitation. Recent randomized clinical trials all emphasize the requirement for intense progressive rehabilitation programs to optimally enhance recovery. Moreover, advances in multimodal assessment of patients with neuroimaging and neurophysiological tools suggest the possibility of individualized treatment plans based on recovery potential. There are also promising indications for medical as well as noninvasive brain stimulation paradigms to facilitate recovery. Ongoing or planned clinical studies should provide more definitive evidence. We also highlight unmet needs and potential areas of research. Continued research built upon a robust experimental and theoretical foundation should help to develop novel treatments to improve recovery after neurological injury. Ann Neurol 2013;74:373-381 C1 [Ganguly, Karunesh; Abrams, Gary M.] Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, Dept Neurol & Rehabil, San Francisco, CA 94143 USA. [Ganguly, Karunesh; Abrams, Gary M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Byl, Nancy N.] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, San Francisco, CA 94143 USA. RP Ganguly, K (reprint author), 127 Neurol,4150 Clement St, San Francisco, CA 94121 USA. EM Karunesh.Ganguly@ucsf.edu FU Department of Veterans Affairs [B6674W]; American Heart Association [0875016N]; Burroughs Wellcome Fund (CAMS); University of California, California Institute for Technology, Research and Innovation Science (CITRIS) [A115093, P0036258] FX Supported by grants to K. G. and G. A. from the Department of Veterans Affairs (B6674W) and to K. G. from the American Heart Association (0875016N) and the Burroughs Wellcome Fund (CAMS). Also supported by funding to N.N.B. from the University of California, California Institute for Technology, Research and Innovation Science (CITRIS) Award# A115093, P0036258 (PI Jacob Rosen). NR 105 TC 4 Z9 4 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2013 VL 74 IS 3 BP 373 EP 381 DI 10.1002/ana.23994 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 232BJ UT WOS:000325463100013 PM 25813243 ER PT J AU Li, PY Gan, Y Sun, BL Zhang, F Lu, BF Gao, YQ Liang, WM Thomson, AW Chen, J Hu, XM AF Li, Peiying Gan, Yu Sun, Bao-Liang Zhang, Feng Lu, Binfeng Gao, Yanqin Liang, Weimin Thomson, Angus W. Chen, Jun Hu, Xiaoming TI Adoptive Regulatory T-Cell Therapy Protects Against Cerebral Ischemia SO ANNALS OF NEUROLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; EXPERIMENTAL STROKE; NEUTROPHIL INFILTRATION; REG CELLS; IN-VIVO; MATRIX-METALLOPROTEINASE-9; DISEASE; INJURY; GAMMA; VITRO AB ObjectiveRecent evidence suggests that functional deficiency in regulatory T cells (Tregs), an innate immunomodulator, exacerbates brain damage after cerebral ischemia. We therefore evaluated the effect of Treg transfer in rodent models of ischemic stroke and further investigated the mechanism underlying Treg-afforded neuroprotection. MethodsWe examined the therapeutic potential of Tregs and the mechanisms of neuroprotection in vivo in 2 rodent models of ischemic stroke and in vitro in Treg-neutrophil cocultures using a combined approach including cell-specific depletion, gene knockout mice, and bone marrow chimeras. ResultsSystemic administration of purified Tregs at 2, 6, or even 24 hours after middle cerebral artery occlusion resulted in a marked reduction of brain infarct and prolonged improvement of neurological functions lasting out to 4 weeks. Treg-afforded neuroprotection was accompanied by attenuated blood-brain barrier (BBB) disruption during early stages of ischemia, decreased cerebral inflammation, and reduced infiltration of peripheral inflammatory cells into the lesioned brain. Surprisingly, Tregs exerted early neuroprotection without penetrating into the brain parenchyma or inhibiting the activation of residential microglia. Rather, both in vivo and in vitro studies demonstrated that Tregs suppressed peripheral neutrophil-derived matrix metallopeptidase-9 production, thus preventing proteolytic damage of the BBB. In addition to its potent central neuroprotection, Treg treatment was shown to ameliorate poststroke lymphopenia, suggesting a beneficial effect on immune status. InterpretationOur study suggests that Treg adoptive therapy is a novel and potent cell-based therapy targeting poststroke inflammatory dysregulation and neurovascular disruption. Ann Neurol 2013;74:458-471 C1 [Li, Peiying; Zhang, Feng; Gao, Yanqin; Liang, Weimin; Chen, Jun; Hu, Xiaoming] Fudan Univ, Huashan Hosp, Dept Anesthesiol, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Li, Peiying; Zhang, Feng; Gao, Yanqin; Liang, Weimin; Chen, Jun; Hu, Xiaoming] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Li, Peiying; Gan, Yu; Zhang, Feng; Chen, Jun; Hu, Xiaoming] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA USA. [Sun, Bao-Liang] Shandong Univ, Affiliated Hosp, Taishan Med Coll, Dept Neurol, Tai An, Shandong, Peoples R China. [Sun, Bao-Liang] Shandong Univ, Affiliated Hosp, Taishan Med Coll, Key Lab Cerebral Microcirculat, Tai An, Shandong, Peoples R China. [Lu, Binfeng; Thomson, Angus W.] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. [Thomson, Angus W.] Univ Pittsburgh, Sch Med, Dept Surg, Starzl Transplantat Inst, Pittsburgh, PA USA. [Chen, Jun; Hu, Xiaoming] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Hu, XM (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu; hux2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU Veterans Health Administration (GRECC); NIH NINDS [NS36736, NS43802, NS45048]; American Heart Association [10POST4150028, 10SDG2560122]; Chinese Natural Science Foundation [8107094] FX This work was supported by the Veterans Health Administration (GRECC pilot grant to J.C.), NIH NINDS grants (NS36736, NS43802, and NS45048 to J.C.), and grants from the American Heart Association (10POST4150028 to X. H., 10SDG2560122 to F.Z.). B.-L. S. was supported by Chinese Natural Science Foundation grants (8107094). NR 38 TC 48 Z9 51 U1 5 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2013 VL 74 IS 3 BP 458 EP 471 DI 10.1002/ana.23815 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 232BJ UT WOS:000325463100024 PM 23674483 ER PT J AU Baruch, L Sherman, O AF Baruch, Lawrence Sherman, Olga TI Inaccuracy of Point-of-Care International Normalized Ratio in Rivaroxaban-Treated Patients SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE rivaroxaban; point-of-care INR; INR; anticoagulation; factor Xa inhibitor; deep vein thrombosis AB Objective: To report 2 cases in which point-of-care international normalized ratios (POC-INRs) measured using a Hemochron Jr. Signature Elite device (International Technidyne Corporation) were inaccurate in rivaroxaban-treated patients. Case Summaries: Therapy in an 86-year-old man with atrial fibrillation was converted from warfarin to rivaroxaban 15 mg twice daily because of a deep venous thrombotic event despite an INR of 2.4, which was within the therapeutic range. One week later a POC-INR was inadvertently measured, which was 6.3. In light of the POC-INR being markedly elevated, a laboratory test for INR was performed, which gave a result of 2.74. Therapy in a 66-year-old man was converted from war-farin to rivaroxaban 15 mg twice daily because of unstable INRs and a pulmonary embolism despite a therapeutic INR. Seven days after rivaroxaban was started, the patient's POC-INR was 9.2; simultaneously measured laboratory-determined INR was 2.0. For both patients, coagulation tests performed on follow-up visits revealed continued discordance between the POC and laboratory assays. Discussion: Rivaroxaban is an oral factor Xa inhibitor with a predictable pharmacokinetic profile, allowing for a fixed-dose regimen without the need for coagulation monitoring. When patients' therapy is switched from rivaroxaban to warfarin, it is recommended that the drugs be given concurrently until the INR is 2.0 or higher, to ensure adequate anticoagulation during this well-recognized vulnerable period for stroke. POC testing is a common method of INR assessment in clinical practice. During 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), POC-INRs were measured exclusively with the INRatio device (Hemosense), and values above 4 were seen very rarely (0.25%), which indicates that the values determined in our patients were highly unusual. Conclusions: Our 2 patients receiving rivaroxaban had POC-INRs elevated beyond what was expected; these measurements were discordant from INRs simultaneously measured via the laboratory. A prospective evaluation assessing the accuracy of other commonly used POC-INR devices in patients receiving rivaroxaban would determine whether our findings extend to other devices. Until that time, laboratory measurement of INR or POC-INR using an INRatio device is recommended when patients' therapy is transitioned from rivaroxaban to warfarin. C1 [Baruch, Lawrence] James J Peters VA Med Ctr, Program Med, Bronx, NY USA. [Baruch, Lawrence] Mt Sinai Sch Med, Dept Cardiol, New York, NY USA. [Sherman, Olga] James J Peters VA Med Ctr, Pharm Program, Bronx, NY USA. RP Baruch, L (reprint author), James J Peters VA Med Ctr, Program Med, Bronx, NY USA. EM lawrence.baruch@va.gov NR 1 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD SEP PY 2013 VL 47 IS 9 BP 1210 EP 1212 DI 10.1177/1060028013503129 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225UR UT WOS:000324989700014 PM 24259738 ER PT J AU Savoia, E Lin, L Viswanath, K AF Savoia, Elena Lin, Leesa Viswanath, Kasisomayajula TI COMMUNICATIONS IN PUBLIC HEALTH EMERGENCY PREPAREDNESS: A SYSTEMATIC REVIEW OF THE LITERATURE SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE LA English DT Article ID RISK COMMUNICATION; PANDEMIC INFLUENZA; AVIAN INFLUENZA; INFORMATION-SOURCES; NATURAL DISASTERS; MASS-MEDIA; RADIOLOGICAL/NUCLEAR TERRORISM; VULNERABLE POPULATIONS; COMMUNITY MITIGATION; DISEASE OUTBREAKS AB During a public health crisis, public health agencies engage in a variety of public communication efforts to inform the population, encourage the adoption of preventive behaviors, and limit the impact of adverse events. Given the importance of communication to the public in public health emergency preparedness, it is critical to examine the extent to which this field of study has received attention from the scientific community. We conducted a systematic literature review to describe current research in the area of communication to the public in public health emergency preparedness, focusing on the association between sociodemographic and behavioral factors and communication as well as preparedness outcomes. Articles were searched in PubMed and Embase and reviewed by 2 independent reviewers. A total of 131 articles were included for final review. Fifty-three percent of the articles were empirical, of which 74% were population-based studies, and 26% used information environment analysis techniques. None had an experimental study design. Population-based studies were rarely supported by theoretical models and mostly relied on a cross-sectional study design. Consistent results were reported on the association between population socioeconomic factors and public health emergency preparedness communication and preparedness outcomes. Our findings show the need for empirical research to determine what type of communication messages can be effective in achieving preparedness outcomes across various population groups. They suggest that a real-time analysis of the information environment is valuable in knowing what is being communicated to the public and could be used for course correction of public health messages during a crisis. C1 [Savoia, Elena] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Savoia, Elena] Harvard Univ, Sch Publ Hlth, Div Policy Translat & Leadership Dev, Boston, MA 02115 USA. [Lin, Leesa; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Lin, Leesa; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lin, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Landmark Ctr,PERRC, 677 Huntington Ave,3rd Floor East, Boston, MA 02115 USA. EM llin@hsph.harvard.edu FU OPHPR CDC HHS [5P01TP000307-05] NR 152 TC 6 Z9 6 U1 3 U2 37 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-7135 EI 1557-850X J9 BIOSECUR BIOTERROR JI Biosecur. Bioterror. PD SEP 1 PY 2013 VL 11 IS 3 BP 170 EP 184 DI 10.1089/bsp.2013.0038 PG 15 WC Public, Environmental & Occupational Health; International Relations SC Public, Environmental & Occupational Health; International Relations GA 218JL UT WOS:000324428600002 PM 24041193 ER PT J AU Yonetsu, T Kato, K Uemura, S Kim, BK Jang, Y Kang, SJ Park, SJ Lee, S Kim, SJ Jia, HB Vergallo, R Abtahian, F Tian, JW Hu, SN Yeh, RW Sakhuja, R McNulty, I Lee, H Zhang, SS Yu, B Kakuta, T Jang, IK AF Yonetsu, Taishi Kato, Koji Uemura, Shiro Kim, Byeong-Keuk Jang, Yangsoo Kang, Soo-Jin Park, Seung-Jung Lee, Stephen Kim, Soo-Joong Jia, Haibo Vergallo, Rocco Abtahian, Farhad Tian, Jinwei Hu, Sining Yeh, Robert W. Sakhuja, Rahul McNulty, Iris Lee, Hang Zhang, Shaosong Yu, Bo Kakuta, Tsunekazu Jang, Ik-Kyung TI Features of Coronary Plaque in Patients With Metabolic Syndrome and Diabetes Mellitus Assessed by 3-Vessel Optical Coherence Tomography SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE diabetes mellitus; metabolic syndrome; plaque; tomography; optical coherence ID CARDIOVASCULAR-DISEASE; INTRAVASCULAR ULTRASOUND; RISK-FACTORS; ATHEROSCLEROSIS; NEOVASCULARIZATION; ACQUISITION; MORPHOLOGY; RUPTURE; DEATH; MEN AB Background The pathophysiological basis for the association between metabolic syndrome (MetS) and coronary artery disease is not well understood. We sought to characterize coronary plaques in patients with MetS by using optical coherence tomography. Methods and Results We identified 451 coronary plaques from 171 subjects who underwent optical coherence tomographic imaging in 3 coronary arteries. Subjects were divided into 3 groups: diabetes mellitus (DM, n=77), MetS (n=35), and a control group (C group, n=59) without DM or MetS. Optical coherence tomographic analysis included the presence of lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index (LI), fibrous cap thickness, and thin-cap fibroatheroma. We defined LI as mean lipid arc multiplied by lipid-core length. Lipid-core length and LI were significantly greater in DM and MetS than in C group (lipid-core length: 7.74.0 and 7.0 +/- 3.8 versus 5.5 +/- 2.4 mm; P<0.001 and P=0.012, and LI: 1164 +/- 716 and 1086 +/- 693 versus 796 +/- 417 mm; P<0.001 and P=0.008). Maximum lipid arc was significantly greater in DM than in C group, whereas no significant difference was observed between MetS and C group (196 +/- 45 degrees, 187 +/- 42 degrees versus 176 +/- 52 degrees; P=0.002 and P=0.182). Fibrous cap thickness and thin-cap fibroatheroma showed no significant difference among the 3 groups. In multivariate analysis, DM and MetS were independently associated with LI, whereas only acute coronary syndrome was the independent predictor for thin-cap fibroatheroma. Conclusions Compared with control subjects, coronary plaques in MetS contain larger lipid. However, the MetS criteria used in this study could not distinguish the vulnerable features such as thin-cap fibroatheroma, suggesting the necessity of complementary information to identify patients at high risk for cardiovascular events. C1 [Yonetsu, Taishi; Kato, Koji; Kang, Soo-Jin; Jia, Haibo; Vergallo, Rocco; Abtahian, Farhad; Tian, Jinwei; Hu, Sining; Yeh, Robert W.; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Kim, Byeong-Keuk; Jang, Yangsoo] Yonsei Univ, Severance Cardiovasc Hosp, Seoul 120749, South Korea. [Kang, Soo-Jin; Park, Seung-Jung] Asan Med Ctr, Seoul, South Korea. [Lee, Stephen] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. [Kang, Soo-Jin] Kyung Hee Univ, Coll Med, Div Cardiol, Seoul, South Korea. [Jia, Haibo; Tian, Jinwei; Hu, Sining; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin 150086, Peoples R China. [Jia, Haibo; Tian, Jinwei; Hu, Sining; Yu, Bo] Chinese Minist Educ, Key Lab Myocardial Ischemia, Harbin, Peoples R China. [Sakhuja, Rahul] Wellmont CVA Heart Inst, Kingsport, TN USA. [Zhang, Shaosong] LightLab Imaging Inc, Westford, MA USA. [Zhang, Shaosong] Harbin Med Univ, Harbin 150086, Peoples R China. [Kakuta, Tsunekazu] Tsuchiura Kyodo Gen Hosp, Tsuchiura, Ibaraki, Japan. RP Yu, B (reprint author), Harbin Med Univ, Chinese Minist Educ, Key Lab Myocardial Ischemia, Dept Cardiol,Affiliated Hosp 2, Harbin 150086, Peoples R China. EM yubodr@163.com FU St. Jude Medical; Dr John Nam Fellowship Grant; Cardiology Division of Massachusetts General Hospital FX This study was supported by research grants from St. Jude Medical, the Cardiology Division of Massachusetts General Hospital, and Dr John Nam Fellowship Grant. NR 34 TC 7 Z9 7 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2013 VL 6 IS 5 BP 665 EP 673 DI 10.1161/CIRCIMAGING.113.000345 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 219RQ UT WOS:000324526900012 PM 23922003 ER PT J AU Cheng, S Larson, MG McCabe, EL Osypiuk, E Lehman, BT Stanchev, P Aragam, J Benjamin, EJ Solomon, SD Vasan, RS AF Cheng, Susan Larson, Martin G. McCabe, Elizabeth L. Osypiuk, Ewa Lehman, Birgitta T. Stanchev, Plamen Aragam, Jayashri Benjamin, Emelia J. Solomon, Scott D. Vasan, Ramachandran S. TI Age- and Sex-Based Reference Limits and Clinical Correlates of Myocardial Strain and Synchrony The Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE echocardiography; left ventricular function; reference values ID SPECKLE-TRACKING ECHOCARDIOGRAPHY; GLOBAL LONGITUDINAL STRAIN; CARDIAC RESYNCHRONIZATION THERAPY; ASE/EAE CONSENSUS STATEMENT; 2-DIMENSIONAL STRAIN; STRESS ECHOCARDIOGRAPHY; MECHANICAL DYSSYNCHRONY; QUANTITATIVE-EVALUATION; MAGNETIC-RESONANCE; ULTRASOUND METHOD AB Background There is rapidly growing interest in applying measures of myocardial strain and synchrony in clinical investigations and in practice; data are limited regarding their reference ranges in healthy individuals. Methods and Results We performed speckle-tracking-based echocardiographic measures of left ventricular myocardial strain and synchrony in healthy adults (n=739, mean age 63 years, 64% women) without cardiovascular disease. Reference values were estimated using quantile regression. Age- and sex-based upper (97.5th quantile) limits were: -14.4% to -17.1% (women) and -14.4 to -15.2% (men) for longitudinal strain; -22.3% to -24.7% (women) and -17.9% to -23.7% (men) for circumferential strain; 121 to 165 ms (women) and 143 to 230 ms (men) for longitudinal segmental synchrony (SD of regional time-to-peak strains); and 200 to 222 ms (women) and 216 to 303 ms (men) for transverse segmental synchrony. In multivariable analyses, women had approximate to 1.7% greater longitudinal strain, approximate to 2.2% greater transverse strain, and approximate to 3.2% greater circumferential strain (P<0.0001 for all) compared with men. Older age and higher diastolic blood pressure, even within the normal range, were associated with worse transverse segmental synchrony (P<0.001). Overall, covariates contributed to 12% of the variation in myocardial strain or synchrony in this healthy sample. Conclusions We estimated age- and sex-specific reference limits for measures of left ventricular strain and synchrony in a healthy community-based sample, wherein clinical covariates contributed to only a modest proportion of the variation. These data may facilitate the interpretation of left ventricular strain-based measures obtained in future clinical research and practice. C1 [Cheng, Susan; Larson, Martin G.; McCabe, Elizabeth L.; Lehman, Birgitta T.; Stanchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 02115 USA. [Larson, Martin G.; McCabe, Elizabeth L.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Aragam, Jayashri] Vet Adm Hosp, Div Cardiovasc, West Roxbury, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Cheng, S (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St,PBB 119, Boston, MA 02115 USA. EM scheng3@partners.org OI Ramachandran, Vasan/0000-0001-7357-5970 FU Ellison Foundation; National Heart, Lung and Blood Institute's Framingham Heart Study [NIH/NHLBI N01-HC-25195]; [NIH/NHLBI K99HL107642]; [NIH/NHLBI R01HL093328] FX This work was supported by the Ellison Foundation (Dr Cheng), the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. NIH/NHLBI N01-HC-25195), and the following grants: NIH/NHLBI K99HL107642 (Dr Cheng) and NIH/NHLBI R01HL093328 (Dr Vasan). The other authors report no conflicts. NR 45 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2013 VL 6 IS 5 BP 692 EP 699 DI 10.1161/CIRCIMAGING.112.000627 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 219RQ UT WOS:000324526900015 PM 23917618 ER PT J AU Abdelbaky, A Corsini, E Figueroa, AL Fontanez, S Subramanian, S Ferencik, M Brady, TJ Hoffmann, U Tawakol, A AF Abdelbaky, Amr Corsini, Erin Figueroa, Amparo L. Fontanez, Sara Subramanian, Sharath Ferencik, Maros Brady, Thomas J. Hoffmann, Udo Tawakol, Ahmed TI Focal Arterial Inflammation Precedes Subsequent Calcification in the Same Location A Longitudinal FDG-PET/CT Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE positron-emission tomography; vascular calcification; arterial inflammation ID POSITRON-EMISSION-TOMOGRAPHY; CAROTID PLAQUE INFLAMMATION; ALL-CAUSE MORTALITY; COMPUTED-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE; VASCULAR CALCIFICATION; ACTIVATED MACROPHAGES; CARDIOVASCULAR EVENTS; AORTIC CALCIFICATION; RISK-FACTORS AB Background Arterial calcium (Ca) deposition has been identified as an active inflammatory process. We sought to test the hypothesis that local vascular inflammation predisposes to subsequent arterial calcium deposition in humans. Methods and Results From a hospital database, we identified 137 patients (age, 6113 years; 48.1% men) who underwent serial positron-emission tomography/computed tomography (1-5 years apart). Focal arterial inflammation was prospectively determined by measuring 18F-flourodeoxyglucose uptake (using baseline positron-emission tomography) within predetermined locations of the thoracic aortic wall and was reported as a standardized uptake value. A separate, blinded investigator evaluated calcium deposition (on the baseline and follow-up computed tomographic scans) along the same standardized sections of the aorta. New calcification was prospectively defined using square root-transformed difference of calcium volume score, with a cutoff value of 2.5. Accordingly, vascular segment was classified as either with or without subsequent calcification. Overall, 67 (9%) of aortic segments demonstrated subsequent calcification. Baseline median (interquartile range) standardized uptake value was higher in segments with versus without subsequent calcification (2.09 [1.84-2.44] versus 1.92 [1.72-2.20], P=0.002). This was also true in the subset of segments with Ca present at baseline (2.08 [1.81-2.40] versus 1.86 [1.66-2.09], P=0.02), as well as those without (2.17 [1.87-2.51] versus 1.93 [1.73-2.20], P=0.04). Furthermore, across all patients, subsequent Ca deposition was associated with the underlying 18F-flourodeoxyglucose uptake (inflammatory signal), measured as standardized uptake value (odds ratio [95% confidence interval]=2.94 [1.27-6.89], P=0.01) or target-to-background ratio (2.59 [1.18-5.70], P=0.02), after adjusting for traditional cardiovascular risk factors. Conclusions Here, we provide first-in-man evidence that arterial inflammation precedes subsequent Ca deposition, a marker of plaque progression, within the underlying location in the artery wall. C1 [Abdelbaky, Amr; Corsini, Erin; Figueroa, Amparo L.; Fontanez, Sara; Subramanian, Sharath; Ferencik, Maros; Brady, Thomas J.; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Ferencik, Maros; Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org NR 36 TC 36 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2013 VL 6 IS 5 BP 747 EP 754 DI 10.1161/CIRCIMAGING.113.000382 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 219RQ UT WOS:000324526900021 PM 23833282 ER PT J AU Beaudoin, J Thai, WE Wai, B Handschumacher, MD Levine, RA Truong, QA AF Beaudoin, Jonathan Thai, Wai-Ee Wai, Bryan Handschumacher, Mark D. Levine, Robert A. Truong, Quynh A. TI Assessment of Mitral Valve Adaptation With Gated Cardiac Computed Tomography Validation With Three-Dimensional Echocardiography and Mechanistic Insight to Functional Mitral Regurgitation SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE 3-dimensional echocardiography; cardiac computed tomography; mitral valve insufficiency ID LEFT-VENTRICULAR SHAPE; HEART-FAILURE; LEAFLET ADAPTATION; ORIFICE AREA; QUANTIFICATION; FLOW; CT; DETERMINANT; DYSFUNCTION; SEVERITY AB Background Mitral valve (MV) enlargement is a compensatory mechanism capable of preventing functional mitral regurgitation (FMR) in dilated ventricles. Total leaflet area and its relation with closure area measured by 3-dimensional (3D) echocardiography have been related to FMR. Whether these parameters can be assessed with other imaging modalities is not known. Our objectives are to compare cardiac computed tomography (CT)-based measurements of MV leaflets with 3D echocardiography and determine the relationship of these metrics to the presence of FMR. Methods and Results We used 2 cohorts of patients who had cardiac CT to measure MV total leaflet, closure, and annulus areas. In cohort 1 (26 patients), we validated these CT metrics to 3D echocardiography. In cohort 2 (66 patients), we assessed the relation of MV size with the presence of FMR in 3 populations: heart failure with FMR, heart failure without FMR, and normal controls. Cardiac CT and 3D echocardiography produced similar results for total leaflet (R-2=0.97), closure (R-2=0.89), and annulus areas (R-2=0.84). MV size was the largest in heart failure without FMR compared with controls and patients with FMR (9.11.7 versus 7.5 +/- 1.0 versus 8.1 +/- 0.9 cm(2)/m(2); P<0.01). Patients with FMR had reduced ratios of total leaflet to closure areas and total leaflet to annulus areas when compared with patients without FMR (P<0.01). Conclusions MV size measured by CT is comparable with 3D echocardiography. MV enlargement in cardiomyopathy suggests leaflet adaptation. Patients with FMR have inadequate adaptation as reflected by decreased ratios of leaflet area and areas determined by ventricle size (annulus and closure areas). These measurements provide additional insight into the mechanism of FMR. C1 [Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Truong, QA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU AHA-Founders Affiliate postdoctoral fellowship, Dallas, TX [10POST4580055]; National Institutes of Health (NIH) [K23HL098370, L30HL093896]; Leducq Foundation, Paris, France [07CVD04]; NIH [K24 HL67434, R01 HL109506]; Qi Imaging, LLC; St. Jude Medical FX Dr Beaudoin is funded by an AHA-Founders Affiliate postdoctoral fellowship grant 10POST4580055, Dallas, TX. Dr Truong received support from National Institutes of Health (NIH) grants K23HL098370 and L30HL093896. Dr Levine received support from grant 07CVD04 of the Leducq Foundation, Paris, France, for the Leducq Transatlantic MITRAL Network, and by NIH K24 HL67434 and R01 HL109506. Dr Truong receives research grants from Qi Imaging, LLC (formerly Ziosoft) and St. Jude Medical. NR 29 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2013 VL 6 IS 5 BP 784 EP 789 DI 10.1161/CIRCIMAGING.113.000561 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 219RQ UT WOS:000324526900026 PM 23873402 ER PT J AU Groeneveld, PW AF Groeneveld, Peter W. TI Can Advanced Healthcare Technology Save Money? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE Editorials; chest pain diagnosis; computed tomographic angiography; emergency medicine; health economics; hospital costs ID CORONARY; ANGIOGRAPHY; PREDICTORS; IMPACT; TRIAL; SCORE; RISK C1 [Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Groeneveld, Peter W.] Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), Univ Penn, Sch Med, 1229 Blockley Hall,423 Serv Dr, Philadelphia, PA 19104 USA. EM petergro@mail.med.upenn.edu NR 13 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2013 VL 6 IS 5 BP 509 EP 510 DI 10.1161/CIRCOUTCOMES.113.000533 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 219RM UT WOS:000324526400003 PM 24021698 ER PT J AU Hulten, E Goehler, A Bittencourt, MS Bamberg, F Schlett, CL Truong, QA Nichols, J Nasir, K Rogers, IS Gazelle, SG Nagurney, JT Hoffmann, U Blankstein, R AF Hulten, Edward Goehler, Alexander Bittencourt, Marcio Sommer Bamberg, Fabian Schlett, Christopher L. Truong, Quynh A. Nichols, John Nasir, Khurram Rogers, Ian S. Gazelle, Scott G. Nagurney, John T. Hoffmann, Udo Blankstein, Ron TI Cost and Resource Utilization Associated With Use of Computed Tomography to Evaluate Chest Pain in the Emergency Department The Rule Out Myocardial Infarction Using Computer Assisted Tomography (ROMICAT) Study SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute coronary syndrome; chest pain; multidetector computed tomography; economics ID CORONARY-ARTERY-DISEASE; AMERICAN-HEART-ASSOCIATION; CT ANGIOGRAPHY; CLINICAL-OUTCOMES; DIAGNOSTIC PERFORMANCE; MAGNETIC-RESONANCE; PROGNOSTIC VALUE; EARLY TRIAGE; TASK-FORCE; PERFUSION AB Background Coronary computed tomographic angiography (cCTA) allows rapid, noninvasive exclusion of obstructive coronary artery disease (CAD). However, concern exists whether implementation of cCTA in the assessment of patients presenting to the emergency department with acute chest pain will lead to increased downstream testing and costs compared with alternative strategies. Our aim was to compare observed actual costs of usual care (UC) with projected costs of a strategy including early cCTA in the evaluation of patients with acute chest pain in the Rule Out Myocardial Infarction Using Computer Assisted Tomography I (ROMICAT I) study. Methods and Results We compared cost and hospital length of stay of UC observed among 368 patients enrolled in the ROMICAT I study with projected costs of management based on cCTA. Costs of UC were determined by an electronic cost accounting system. Notably, UC was not influenced by cCTA results because patients and caregivers were blinded to the cCTA results. Costs after early implementation of cCTA were estimated assuming changes in management based on cCTA findings of the presence and severity of CAD. Sensitivity analysis was used to test the influence of key variables on both outcomes and costs. We determined that in comparison with UC, cCTA-guided triage, whereby patients with no CAD are discharged, could reduce total hospital costs by 23% (P<0.001). However, when the prevalence of obstructive CAD increases, index hospitalization cost increases such that when the prevalence of 50% stenosis is >28% to 33%, the use of cCTA becomes more costly than UC. Conclusions cCTA may be a cost-saving tool in acute chest pain populations that have a prevalence of potentially obstructive CAD <30%. However, increased cost would be anticipated in populations with higher prevalence of disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00990262. C1 [Hulten, Edward; Bittencourt, Marcio Sommer; Blankstein, Ron] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Hulten, Edward; Bittencourt, Marcio Sommer; Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Cardiovasc Div, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Hulten, Edward; Bittencourt, Marcio Sommer; Blankstein, Ron] Harvard Univ, Sch Med, Boston, MA USA. [Goehler, Alexander; Schlett, Christopher L.; Nichols, John; Nagurney, John T.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Goehler, Alexander] Yale Univ, Dept Radiol, New Haven, CT USA. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-80539 Munich, Germany. [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Nasir, Khurram] Baptist Hlth South Florida, Miami, FL USA. [Rogers, Ian S.] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA. [Gazelle, Scott G.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Gazelle, Scott G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Hulten, E (reprint author), Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, 75 Francis St, Boston, MA 02115 USA. EM ehulten@partners.org RI Bittencourt, Marcio/C-1444-2011; OI Bittencourt, Marcio/0000-0002-3711-1754; Hulten, Edward/0000-0001-9281-0032 FU National Institutes of Health (NIH) [R01 HL080053]; Siemens Medical Solutions; GE Healthcare; NIH [K23HL098370, L30HL093896] FX This work was supported by the National Institutes of Health (NIH) R01 HL080053 and supported in part by Siemens Medical Solutions and GE Healthcare. Dr Truong was supported by NIH grants K23HL098370 and L30HL093896. NR 41 TC 12 Z9 12 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2013 VL 6 IS 5 BP 514 EP 524 DI 10.1161/CIRCOUTCOMES.113.000244 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 219RM UT WOS:000324526400005 PM 24021693 ER PT J AU Schwamm, LH Ali, SF Reeves, MJ Smith, EE Saver, JL Messe, S Bhatt, DL Grau-Sepulveda, MV Peterson, ED Fonarow, GC AF Schwamm, Lee H. Ali, Syed F. Reeves, Mathew J. Smith, Eric E. Saver, Jeffrey L. Messe, Steven Bhatt, Deepak L. Grau-Sepulveda, Maria V. Peterson, Eric D. Fonarow, Gregg C. TI Temporal Trends in Patient Characteristics and Treatment With Intravenous Thrombolysis Among Acute Ischemic Stroke Patients at Get With the Guidelines-Stroke Hospitals SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cerebrovascular disorders; ischemic attack; transient; thrombolysis; therapeutic ID TISSUE-PLASMINOGEN ACTIVATOR; UNITED-STATES; ASSOCIATION; CARE; TPA; ELIGIBILITY; OUTCOMES; REGISTRY; THERAPY; PROGRAM AB Background Substantial efforts over the past decade have increased rates of intravenous tissue plasminogen activator (tPA) use in the United States. We sought to determine changes in patient characteristics and rates of tPA use over time among hospitalized acute ischemic stroke (AIS) patients. Methods and Results We analyzed all AIS patients (n=1093895) and those arriving 2 hours and treated with tPA 3 hours after onset (n=50798) from 2003 to 2011 in the American Heart Association's Get with the Guideline-Stroke (GWTG-Stroke). Categorical data were analyzed by Pearson (2) and continuous data by Wilcoxon test. Intravenous tPA use 3 hours after onset increased from 4.0% to 7.0% in all AIS admissions and 42.6% to 77.0% in AIS patients arriving 2 hours and fully eligible for tPA (P<0.001). In univariate analysis, tPA use increased over time, especially in those aged >85 years, nonwhite, and with milder strokes (National Institutes of Health Stroke Scale 0-4). Door-to-image time (median 24 versus 20 minutes) and door-to-tPA time (median 81 versus 72 minutes) also improved, with approximate to 65% of tPA-treated patients getting brain imaging 25 minutes after arrival. Multivariable analysis showed that with each additional calendar year, the odds that an eligible patient would receive tPA increased by 1.37-fold, adjusting for other covariates. Conclusions The frequency of IV tPA use among all AIS patients, regardless of contraindications, nearly doubled from 2003 to 2011. Treatment with tPA has expanded to include more patients with mild deficits, nonwhite race/ethnicity, and oldest old age. C1 [Schwamm, Lee H.; Ali, Syed F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Saver, Jeffrey L.; Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Messe, Steven] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA. [Grau-Sepulveda, Maria V.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. RP Schwamm, LH (reprint author), Harvard Univ, Dept Neurol, MGH, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; Janseen Pharmaceutical Companies of Johnson Johnson; American Heart Association Pharmaceutical Roundtable FX The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janseen Pharmaceutical Companies of Johnson & Johnson, and the American Heart Association Pharmaceutical Roundtable. Dr Bhatt discloses the following relationships: Advisory Board, Medscape Cardiology; Board of Directors, Boston VA Research Institute, Society of Chest Pain Centers; Chair, American Heart Association Get With The Guidelines Science Subcommittee; Honoraria, American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Other, Senior Associate Editor, Journal of Invasive Cardiology; Research Grants, Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research, FlowCo, PLx Pharma, Takeda. The other authors report no conflicts. NR 26 TC 62 Z9 63 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2013 VL 6 IS 5 BP 543 EP 549 DI 10.1161/CIRCOUTCOMES.111.000303 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 219RM UT WOS:000324526400008 PM 24046398 ER PT J AU Canavan, C Eisenburg, J Meng, L Corey, K Hur, C AF Canavan, C. Eisenburg, J. Meng, L. Corey, K. Hur, C. TI Ultrasound Elastography for Fibrosis Surveillance Is Cost Effective in Patients with Chronic Hepatitis C Virus in the UK SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Hepatitis C; Liver fibrosis; Hepatocellular carcinoma; Screening; Health economics; Outcomes research; Radiology/imaging ID SMALL HEPATOCELLULAR-CARCINOMA; CHRONIC LIVER-DISEASE; GENOTYPE 1 INFECTION; TRANSIENT ELASTOGRAPHY; PROGRESSION RATES; RISK-FACTORS; CIRRHOSIS; TRANSPLANTATION; MORTALITY; METAANALYSIS AB Background Chronic hepatitis C (HCV) is a significant risk factor for cirrhosis and subsequently hepatocellular carcinoma (HCC). HCV patients with cirrhosis are screened for HCC every 6 months. Surveillance for progression to cirrhosis and consequently access to HCC screening is not standardized. Liver biopsy, the usual test to determine cirrhosis, carries a significant risk of morbidity and associated mortality. Transient ultrasound elastography (fibroscan) is a non-invasive test for cirrhosis. Purpose This study assesses the cost effectiveness of annual surveillance for cirrhosis in patients with chronic HCV and the effect of replacing biopsy with fibroscan to diagnose cirrhosis. Method A Markov decision analytic model simulated a hypothetical cohort of 10,000 patients with chronic HCV initially without fibrosis over their lifetime. The cirrhosis surveillance strategies assessed were: no surveillance; current practice; fibroscan in current practice with biopsy to confirm cirrhosis; fibroscan completely replacing biopsy in current practice (definitive); annual biopsy; annual fibroscan with biopsy to confirm cirrhosis; annual definitive fibroscan. Results Our results demonstrate that annual definitive fibroscan is the optimal strategy to diagnose cirrhosis. In our study, it diagnosed 20 % more cirrhosis cases than the current strategy, with 549 extra patients per 10,000 accessing screening over a lifetime and, consequently, 76 additional HCC cases diagnosed. The lifetime cost is 98.78 pound extra per patient compared to the current strategy for 1.72 additional unadjusted life years. Annual fibroscan surveillance of 132 patients results in the diagnosis one additional HCC case over a lifetime. The incremental cost-effectiveness ratio for an annual definitive fibroscan is 6,557.06 pound/quality-adjusted life years gained. Conclusion Annual definitive fibroscan may be a cost-effective surveillance strategy to identify cirrhosis in patients with chronic HCV, thereby allowing access of these patients to HCC screening. C1 [Canavan, C.] Univ Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG5 1PB, England. [Eisenburg, J.; Meng, L.; Hur, C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Corey, K.; Hur, C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Canavan, C (reprint author), Univ Nottingham, Div Epidemiol & Publ Hlth, Clin Sci Bldg,City Hosp Campus,Hucknall Rd, Nottingham NG5 1PB, England. EM mczcpc@nottingham.ac.uk OI Hur, Chin/0000-0002-2819-7576 FU MRC [RA0837] FX CC is funded by MRC Population Health Scientist Fellowship RA0837. NR 71 TC 11 Z9 11 U1 2 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2013 VL 58 IS 9 BP 2691 EP 2704 DI 10.1007/s10620-013-2705-y PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 215YE UT WOS:000324246300055 PM 23720196 ER PT J AU Liu, LY Fox, CS North, TE Goessling, W AF Liu, Leah Y. Fox, Caroline S. North, Trista E. Goessling, Wolfram TI Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development SO DISEASE MODELS & MECHANISMS LA English DT Article ID NONALCOHOLIC FATTY LIVER; GENOME-WIDE ASSOCIATION; HEREDITARY FRUCTOSE INTOLERANCE; HEPATIC STEATOSIS; SUSCEPTIBILITY; ACETAMINOPHEN; VARIANTS; DISEASE; DISRUPTION; PROMOTER AB Genome-wide association studies (GWAS) have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf) and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10) decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50) decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes. C1 [Liu, Leah Y.; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Fox, Caroline S.] Ctr Populat Studies, Framingham, MA 01702 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [North, Trista E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [North, Trista E.; Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA. [Goessling, Wolfram] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. RP Goessling, W (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. EM wgoessling@partners.org OI Goessling, Wolfram/0000-0001-9972-1569 FU Harvard Stem Cell Institute; National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK090311]; National Science Foundation FX This work was supported by a seed grant from the Harvard Stem Cell Institute and the National Institute of Diabetes and Digestive and Kidney Diseases 1R01DK090311 (to W.G.). L.Y.L. was supported by the National Science Foundation. NR 33 TC 6 Z9 6 U1 2 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD SEP PY 2013 VL 6 IS 5 BP 1271 EP 1278 DI 10.1242/dmm.011726 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 236IV UT WOS:000325789600022 PM 23813869 ER PT J AU Holmes, AK Rauch, PK Cozza, SJ AF Holmes, Allison K. Rauch, Paula K. Cozza, Stephen J. TI When a Parent Is Injured or Killed in Combat SO FUTURE OF CHILDREN LA English DT Article ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; BEREAVED CHILDREN; PSYCHOLOGICAL DISTRESS; PROVIDER PERSPECTIVES; VIETNAM VETERANS; TERM ADJUSTMENT; SERVICE MEMBERS; WAR VETERANS AB When a service member is injured or dies in a combat zone, the consequences for his or her family can be profound and long-lasting. Visible, physical battlefield injuries often require families to adapt to long and stressful rounds of treatment and rehabilitation, and they can leave the service member with permanent disabilities that mean new roles for everyone in the family. Invisible injuries, both physical and psychological, including traumatic brain injury and combat-related stress disorders, are often not diagnosed until many months after a service member returns from war (if they are diagnosed at all-many sufferers never seek treatment). They can alter a service member's behavior and personality in ways that make parenting difficult and reverberate throughout the family. And a parent's death in combat not only brings immediate grief but can also mean that survivors lose their very identity as a military family when they must move away from their supportive military community. Sifting through the evidence on both military and civilian families, Allison Holmes, Paula Rauch, and Stephen Cozza analyze, in turn, how visible injuries, traumatic brain injuries, stress disorders, and death affect parents' mental health, parenting capacity, and family organization; they also discuss the community resources that can help families in each situation. They note that most current services focus on the needs of injured service members rather than those of their families. Through seven concrete recommendations, they call for a greater emphasis on family-focused care that supports resilience and positive adaptation for all members of military families who are struggling with a service member's injury or death. C1 [Holmes, Allison K.; Cozza, Stephen J.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Rauch, Paula K.] Massachusetts Gen Hosp Home Base Team, Boston, MA USA. [Rauch, Paula K.] Harvard Univ, Med School, Cambridge, MA 02138 USA. [Cozza, Stephen J.] US Army, Adelphi, MD USA. RP Holmes, AK (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. NR 82 TC 10 Z9 10 U1 2 U2 10 PU PRINCETON UNIV PI PRINCETON PA 277 WALLACE HALL, PRINCETON, NJ 08544 USA SN 1054-8289 EI 1550-1558 J9 FUTURE CHILD JI Future Child. PD FAL PY 2013 VL 23 IS 2 BP 143 EP 162 PG 20 WC Family Studies; Health Policy & Services; Social Sciences, Interdisciplinary SC Family Studies; Health Care Sciences & Services; Social Sciences - Other Topics GA 230FR UT WOS:000325322600008 PM 25518696 ER PT J AU Li, JS Hosseini, A Cancre, L Ryan, N Rubash, HE Li, GA AF Li, Jing-Sheng Hosseini, Ali Cancre, Lucile Ryan, Nolan Rubash, Harry E. Li, Guoan TI Kinematic characteristics of the tibiofemoral joint during a step-up activity SO GAIT & POSTURE LA English DT Article DE Cartilage contact; Condylar motion; In vivo knee kinematics; Step-up activity ID CRUCIATE LIGAMENT DEFICIENCY; FLUOROSCOPIC IMAGING TECHNIQUE; KNEE KINEMATICS; LIVING KNEE; CONTACT POINTS; STANCE PHASE; STAIR ASCENT; MOTION; MRI; MOVEMENT AB The step-up activity (stair-ascending) is an important daily function of the knee. This study aimed to investigate the articular cartilage contact kinematics on both tibial and femoral cartilage surfaces and describe the femoral condylar motion using the transepicondylar axis (TEA) and the geometric center axis (GCA) during a step-up activity. Twenty-one healthy subjects were included and their knee joint models were reconstructed using MR images. A single-stair step-up activity was imaged using a dual-fluoroscopic imaging system. Three-dimensional knee joint contact points were determined and projected onto the tibial plateau and femoral condylar surfaces. The contact points on the medial and lateral tibial plateau moved anteriorly (by 13.5 +/- 3.2 and 10.7 +/- 5.0 mm, respectively, p > 0.05) with knee extension. The contact points on the medial and lateral femoral condyle moved from the posterior to the anterior portion (by 32.2 +/- 4.9 mm and 25.5 +/- 4.2 mm, respectively, p < 0.05) and were located on the inner half of the femoral cartilage throughout the activity. The data on articular contact kinematics and the femoral condylar motion described using the TEA and GCA indicated that the medial and lateral compartments had similar motion patterns during the step-up activity. The knee does not demonstrate a medial-pivoting motion character during the step-up activity. The data may provide insight to contemporary TKA development. (C) 2013 Elsevier B.V. All rights reserved. C1 [Li, Jing-Sheng; Hosseini, Ali; Cancre, Lucile; Ryan, Nolan; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Sch Med, Orthopaed Bioengn Lab, Massachusetts Gen Hosp, 55 Fruit St GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institute of Health [R01 AR055612]; Department of Orthopaedic Surgery at Massachusetts General Hospital FX The authors would like to gratefully acknowledge the financial support of the National Institute of Health (R01 AR055612) and the Department of Orthopaedic Surgery at Massachusetts General Hospital. NR 30 TC 10 Z9 11 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 EI 1879-2219 J9 GAIT POSTURE JI Gait Posture PD SEP PY 2013 VL 38 IS 4 BP 712 EP 716 DI 10.1016/j.gaitpost.2013.03.004 PG 5 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 231MV UT WOS:000325421900028 PM 23541765 ER PT J AU Ademi, Z Liew, D Zomer, E Gorelik, A Hollingsworth, B Steg, PG Bhatt, DL Reid, CM AF Ademi, Zanfina Liew, Danny Zomer, Ella Gorelik, Alexandra Hollingsworth, Bruce Steg, Ph. Gabriel Bhatt, Deepak L. Reid, Christopher M. TI Outcomes and Excess Costs among Patients with Cardiovascular Disease SO HEART LUNG AND CIRCULATION LA English DT Article DE Cardiovascular disease; Resource use; Excess costs ID ATHEROTHROMBOTIC DISEASE; REACH REGISTRY; UNITED-STATES; EVENT RATES; AUSTRALIA; RISK; CONSEQUENCES; OUTPATIENTS AB Objective: To report on two-year cardiovascular (CV) event rates and quantify the cost of cardiovascular disease using the Australian Reduction of Atherothrombosis for Continued Health (REACH) registry. Methods: Prospective registry of 2873 patients with multiple risk factors (MRF), coronary artery disease (CAD), cerebrovascular disease (CerVD) and peripheral artery disease (PAD), recruited through 273 Australian general practitioners. Government reimbursement data from 2011 was used to calculate direct health care costs (pharmaceuticals, outpatient and hospitalisation costs). The main outcome of interest was two-year rates and associated excess costs of cardiovascular death, myocardial infarction, stroke, and hospitalisation for cardiovascular procedures. Results: The two year follow-up data were available for 2856 (99.4%) patients. Incidence of any hospitalisation and cardiovascular death was highest among those with previous history of PAD at baseline 49% (n = 126), and 5.1% (n = 13). Non-fatal cardiovascular events were highest among the PAD and CAD groups (21.8% (n = 56) and 14.1% (n = 297) respectively). Those with previous history of PAD and CerVD at baseline had the highest likelihood of CV death (OR = 2.53(95% CI: 1.58-4.08) and OR = 1.61 (1.05-2.46) respectively) in comparison to other groups. Patients with PAD had the highest likelihood of vascular interventions OR = 3.11 (95% CI: 2.09-4.63) at two years. Overall, the mean (SD) direct expenditure over two years of follow-up per person was A$7544 (A$10,758). In the adjusted model, patients with CAD and PAD incurred A$1093 (95% CI A$24 - A$2072) and A$4890 (95% CI A$3105 - A$6869) more in mean total costs compared to patients with MRF. Conclusions: Patients with PAD had the highest likelihood of vascular interventions and CV death, and incurred high excess costs in comparison to other groups. (C) 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved. C1 [Ademi, Zanfina; Liew, Danny; Gorelik, Alexandra] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne EpiCtr, Melbourne, Vic 3010, Australia. [Ademi, Zanfina; Zomer, Ella; Reid, Christopher M.] Monash Univ, Dept Epidemiol & Prevent Med, Clayton, Vic 3800, Australia. [Hollingsworth, Bruce] Univ Lancaster, Div Hlth Res, Lancaster LA1 4YW, England. [Steg, Ph. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Steg, Ph. Gabriel] AP HP, Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ademi, Z (reprint author), Royal Melbourne Hosp, Melbourne EpiCtr, 7 East,Main Bldg,Grattan St, Parkville, Vic 3050, Australia. EM zademi@unimelb.edu.au OI Hollingsworth, Bruce/0000-0002-4314-6523; Liew, Danny/0000-0002-0131-623X; Gorelik, Alexandra/0000-0003-1032-0457 FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan) FX The global REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb and the Waksman Foundation (Tokyo, Japan), and is endorsed by the World Heart Federation. The REACH Registry enforces a no-ghostwriting policy. The sponsors provide logistical support. All manuscripts in the REACH Registry are led by independent authors who are not governed by the funding sponsors and are reviewed by an academic publication committee before submission. The funding sponsors have the opportunity to review manuscript submissions but do not have authority to change any aspect of a manuscript. A complete list of the REACH Registry Investigators appears in JAMA. 2006; 295(2): 180-189. NR 22 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1443-9506 EI 1444-2892 J9 HEART LUNG CIRC JI Heart Lung Circ. PD SEP PY 2013 VL 22 IS 9 BP 724 EP 730 DI 10.1016/j.hlc.2013.02.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 233TK UT WOS:000325592200006 PM 23510668 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Thomas Ince: Hollywood's independent pioneer SO HISTORICAL JOURNAL OF FILM RADIO AND TELEVISION LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0143-9685 EI 1465-3451 J9 HIST J FILM RADIO TV JI Hist. J. Film Radio Telev. PD SEP 1 PY 2013 VL 33 IS 3 SI SI BP 495 EP 499 PG 5 WC Film, Radio, Television SC Film, Radio & Television GA 222HZ UT WOS:000324723100020 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Col. William N. Selig, the Man who Invented Hollywood SO HISTORICAL JOURNAL OF FILM RADIO AND TELEVISION LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0143-9685 EI 1465-3451 J9 HIST J FILM RADIO TV JI Hist. J. Film Radio Telev. PD SEP 1 PY 2013 VL 33 IS 3 SI SI BP 495 EP 499 PG 5 WC Film, Radio, Television SC Film, Radio & Television GA 222HZ UT WOS:000324723100019 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI The Sounds of the Silents in Britain SO HISTORICAL JOURNAL OF FILM RADIO AND TELEVISION LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0143-9685 EI 1465-3451 J9 HIST J FILM RADIO TV JI Hist. J. Film Radio Telev. PD SEP 1 PY 2013 VL 33 IS 3 SI SI BP 499 EP 500 DI 10.1080/01439685.2013.822662 PG 2 WC Film, Radio, Television SC Film, Radio & Television GA 222HZ UT WOS:000324723100021 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Moving Color: early film, mass culture, modernism SO HISTORICAL JOURNAL OF FILM RADIO AND TELEVISION LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp Arch, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0143-9685 EI 1465-3451 J9 HIST J FILM RADIO TV JI Hist. J. Film Radio Telev. PD SEP 1 PY 2013 VL 33 IS 3 SI SI BP 501 EP 502 DI 10.1080/01439685.2013.822663 PG 2 WC Film, Radio, Television SC Film, Radio & Television GA 222HZ UT WOS:000324723100022 ER PT J AU Robbins, GK Testa, MA Su, M Safren, SA Morse, G Lammert, S Shafer, RW Reynolds, NR Chesney, MA AF Robbins, Gregory K. Testa, Marcia A. Su, Max Safren, Steven A. Morse, Gene Lammert, Sara Shafer, Robert W. Reynolds, Nancy R. Chesney, Margaret A. TI Site Nurse-Initiated Adherence and Symptom Support Telephone Calls for HIV-Positive Individuals Starting Antiretroviral Therapy, ACTG 5031: Substudy of ACTG 384 SO HIV CLINICAL TRIALS LA English DT Article DE adherence intervention; antiretroviral therapy; human immunodeficiency virus (HIV); nursing telephone support; randomized controlled trial ID RANDOMIZED-CONTROLLED-TRIALS; SEQUENTIAL 3-DRUG REGIMENS; SELF-REPORTED ADHERENCE; COMBINATION THERAPY; MEDICATION ADHERENCE; INCREASE ADHERENCE; INHIBITOR THERAPY; UNITED-STATES; INFECTION; INTERVENTIONS AB Background: Effective and easy to implement interventions to improve adherence to antiretroviral therapy are needed. Objective: To compare site nurse-initiated adherence and symptom support telephone calls for HIV-positive individuals starting antiretroviral therapy to the study site's standard of care. Methods: A randomized controlled trial of site nurse-initiated adherence and symptom support telephone calls for HIV-positive individuals starting antiretroviral therapy. Subjects were randomized to receive site nurse-initiated telephone calls (intervention) or no additional calls to the site's standard of care (control). Subjects received calls 1 to 3 days after initiating antiretrovirals, on weeks 1, 2, 3, 6, 10, 14, 18, 22, and 26, and every 8 weeks thereafter. Self-reported adherence was captured during study visits. Results: A total of 333 subjects starting antiretrovirals as part of ACTG 384 were co-enrolled into ACTG 5031. Subjects were followed for up to 160 weeks and were contacted for 74% of scheduled calls. There was no significant difference in proportion of patients with >95% mean total adherence (87.9% and 91.2%; P = .34) and mean self-reported total adherence (97.9% and 98.4%) in the intervention and control groups, respectively, or in symptom distress and clinical endpoints. Conclusions: In the context of a clinical trial where self-reported adherence was exceptionally high, the site nurse-initiated telephone calls did not further improve self-reported adherence, symptom distress, or clinical outcomes. C1 [Robbins, Gregory K.; Lammert, Sara] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Robbins, Gregory K.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Testa, Marcia A.] Harvard Sch Publ Hlth, Boston, MA USA. [Su, Max] Phase V Technol Inc, Boston, MA USA. [Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Morse, Gene] SUNY Buffalo, Buffalo, NY 14260 USA. [Shafer, Robert W.] Stanford Univ, Div Infect Dis, Stanford, CA 94305 USA. [Reynolds, Nancy R.] Yale Univ, New Haven, CT USA. [Chesney, Margaret A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Robbins, GK (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM Grobbins@partners.org FU National Institute of Allergy and Infectious Diseases [AI062435, UM1AI068636]; National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR); Harvard University [AI069472]; New York University [AI069532]; Stanford University [AI069556]; University California, Los Angeles [AI069424]; University California, San Diego [AI069432]; University California, San Francisco [AI069502]; University of Miami [AI069477]; University of Rochester Medical Center [AI069511]; University of Southern California [AI069428]; University of Washington [AI069434]; University of Cincinnati [AI069513]; Case Western Reserve University [AI069501]; Northwestern University [AI069471]; Beth Israel Medical Center [AI069472]; University of Puerto Rico [AI069415]; University of Alabama [AI069452]; University of Colorado [AI069450]; Columbia University [AI069470]; Johns Hopkins University [AI069465]; University of Minnesota; Tulane University; Indiana University; University of Hawaii; Howard University; University of Texas, Galveston FX The study was supported by AI062435 (GKR), UM1AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR) and the following ACTG sites: Harvard University (AI069472), New York University (AI069532), Stanford University (AI069556), University California, Los Angeles (AI069424), University California, San Diego (AI069432), University California, San Francisco (AI069502), University of Miami (AI069477), University of Rochester Medical Center (AI069511), University of Southern California (AI069428), University of Washington (AI069434), University of Cincinnati (AI069513), Case Western Reserve University (AI069501), Northwestern University (AI069471), Beth Israel Medical Center (AI069472), University of Puerto Rico (AI069415), University of Alabama (AI069452), University of Colorado (AI069450), Columbia University (AI069470), Johns Hopkins University (AI069465), and past sites: University of Minnesota, Tulane University, Indiana University, University of Hawaii, Howard University, and University of Texas, Galveston. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. NR 30 TC 5 Z9 5 U1 1 U2 5 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119-3627 USA SN 1528-4336 EI 1945-5771 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD SEP-OCT PY 2013 VL 14 IS 5 BP 235 EP 253 DI 10.1310/hct1405-235 PG 19 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 233SJ UT WOS:000325589500006 PM 24144900 ER PT J AU Nambudiri, VE Mutyambizi, K Walls, AC Fisher, DC Bleday, R Saavedra, AP AF Nambudiri, Vinod E. Mutyambizi, Kudakwashe Walls, Andrew C. Fisher, David C. Bleday, Ronald Saavedra, Arturo P. TI Successful Treatment of Perianal Giant Condyloma Acuminatum in an Immunocompromised Host With Systemic Interleukin 2 and Topical Cidofovir SO JAMA DERMATOLOGY LA English DT Article ID CELLS; TUMOR; WARTS C1 [Nambudiri, Vinod E.; Mutyambizi, Kudakwashe; Walls, Andrew C.; Saavedra, Arturo P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Fisher, David C.; Bleday, Ronald; Saavedra, Arturo P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bleday, Ronald] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Div Colorectal Surg, Boston, MA 02115 USA. RP Saavedra, AP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, 221 Longwood Ave, Boston, MA 02115 USA. EM asoavedra@partners.org NR 9 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 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD SEP PY 2013 VL 149 IS 9 BP 1068 EP 1070 DI 10.1001/jamadermatol.2013.5160 PG 3 WC Dermatology SC Dermatology GA 228SN UT WOS:000325209400009 PM 23824272 ER PT J AU Liu, Y Rhee, DJ AF Liu, Yao Rhee, Douglas J. TI Acute Bilateral Angle Closure SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID UVEAL EFFUSION; GLAUCOMA; TOPIRAMATE C1 [Liu, Yao; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Liu, Yao] Univ Wisconsin, Glaucoma Serv, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53705 USA. RP Liu, Y (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 2870 Univ Ave,Ste 102, Madison, WI 53705 USA. EM yaoliumd@gmail.com NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD SEP PY 2013 VL 131 IS 9 BP 1231 EP 1232 DI 10.1001/jamaophthalmol.2013.5186 PG 2 WC Ophthalmology SC Ophthalmology GA 232HC UT WOS:000325482400019 PM 24030335 ER PT J AU Rae, L Pham, TN Carrougher, G Honari, S Gibran, NS Arnoldo, BD Gamelli, RL Tompkins, RG Herndon, DN AF Rae, Lisa Pham, Tam N. Carrougher, Gretchen Honari, Shari Gibran, Nicole S. Arnoldo, Brett D. Gamelli, Richard L. Tompkins, Ronald G. Herndon, David N. TI Differences in Resuscitation in Morbidly Obese Burn Patients May Contribute to High Mortality SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID BODY-MASS INDEX; SEVERE BLUNT TRAUMA; ORGAN FAILURE; INJURY; METAANALYSIS; IMPACT; RISK; ASSOCIATION; MULTICENTER; OUTCOMES AB The rising number of obese patients poses new challenges for burn care. These may include adjustments in calculations of burn size, resuscitation, ventilator wean, nutritional goals as well as challenges in mobilization. The authors have focused this observational study on resuscitation in the obese patient population in the first 48 hours after burn injury. Previous trauma studies suggest a prolonged time to reach end points of resuscitation in the obese compared to nonobese injured patients. The authors hypothesize that obese patients have worse outcomes after thermal injury and that differences in the response to resuscitation contribute to this disparity. The authors retrospectively analyzed data prospectively collected in a multicenter trial to compare resuscitation and outcomes in patients stratified by National Institutes of Health/World Health Organization body mass index (BMI) classification (BMI: normal weight, 18.5-24.9; overweight, 25-29.9, obese, 30-39.9; morbidly obese, 40). Because of the distribution of body habitus in the obese, total burn size was recalculated for all patients by using the method proposed by Neaman and compared with Lund-Browder estimates. The authors analyzed patients by BMI class for fluids administered and end points of resuscitation at 24 and 48 hours. Multivariate analysis was used to compare morbidity and mortality across BMI groups. The authors identified 296 adult patients with a mean TBSA of 41%. Patient and injury characteristics were similar across BMI categories. No significant differences were observed in burn size calculations by using Neaman vs Lund-Browder formulas. Although resuscitation volumes exceeded the predicted formula in all BMI categories, higher BMI was associated with less fluid administered per actual body weight (P = .001). Base deficit on admission was highest in the morbidly obese group at 24 and 48 hours. Furthermore, the morbidly obese patients did not correct their metabolic acidosis to the extent of their lower BMI counterparts (P values .04 and .03). Complications and morbidities across BMI groups were similar, although examination of organ failure scores indicated more severe organ dysfunction in the morbidly obese group. Compared with being normal weight, being morbidly obese was an independent risk factor for death (odds ratio = 10.1; confidence interval, 1.94-52.5; P = .006). Morbidly obese patients with severe burns tend to receive closer to predicted fluid resuscitation volumes for their actual weight. However, this patient group has persistent metabolic acidosis during the resuscitation phase and is at risk of developing more severe multiple organ failure. These factors may contribute to higher mortality risk in the morbidly obese burn patient. C1 [Rae, Lisa; Pham, Tam N.; Carrougher, Gretchen; Honari, Shari; Gibran, Nicole S.] Univ Washington, Harborview Med Ctr, Med Reg Burn Ctr, Seattle, WA 98104 USA. [Arnoldo, Brett D.] Univ Texas Southwestern, Parkland Mem Hosp, Dallas, TX USA. [Gamelli, Richard L.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herndon, David N.] Univ Texas Med Branch, Galveston, TX 77555 USA. RP Rae, L (reprint author), Harborview Med Ctr, 325 9th Ave,Box 359796, Seattle, WA 98103 USA. FU National Institute of General Medical Sciences [2-U54-GM062119] FX Supported by the Inflammation and the Host Response to Injury ("the Glue Grant") Large-Scale Collaborative Project Award 2-U54-GM062119 from the National Institute of General Medical Sciences. The data set obtained from the Glue Grant program does not reflect the opinions or views of the Inflammation and Host Response to Injury investigators or the National Institutes of General Medical Sciences. NR 28 TC 7 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD SEP-OCT PY 2013 VL 34 IS 5 BP 507 EP 514 DI 10.1097/BCR.0b013e3182a2a771 PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 235GT UT WOS:000325705700012 PM 23966116 ER PT J AU Ulu, A Harris, TR Morisseau, C Miyabe, C Inoue, H Schuster, G Dong, H Iosif, AM Liu, JY Weiss, RH Chiamvimonvat, N Imig, JD Hammock, BD AF Ulu, Arzu Harris, Todd R. Morisseau, Christophe Miyabe, Christina Inoue, Hiromi Schuster, Gertrud Dong, Hua Iosif, Ana-Maria Liu, Jun-Yan Weiss, Robert H. Chiamvimonvat, Nipavan Imig, John D. Hammock, Bruce D. TI Anti-inflammatory Effects of omega-3 Polyunsaturated Fatty Acids and Soluble Epoxide Hydrolase Inhibitors in Angiotensin-II-Dependent Hypertension SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE omega-3 polyunsaturated fatty acids; EPA; DHA; soluble epoxide hydrolase inhibitors; angiotensin-II-dependent hypertension ID PLACEBO-CONTROLLED TRIAL; LONG-CHAIN OMEGA-3-FATTY-ACIDS; BLOOD-PRESSURE; DOCOSAHEXAENOIC ACID; CARDIOVASCULAR-DISEASE; CYTOCHROME-P450 EPOXYGENASES; KNOCKOUT MICE; DOUBLE-BLIND; FISH-OIL; METABOLITES AB The mechanisms underlying the anti-inflammatory and antihypertensive effects of long-chain -3 polyunsaturated fatty acids (-3 PUFAs) are still unclear. The epoxides of an -6 fatty acid, arachidonic acid epoxyeicosatrienoic acids also exhibit antihypertensive and anti-inflammatory effects. Thus, we hypothesized that the major -3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may lower the blood pressure and attenuate renal markers of inflammation through their epoxide metabolites. Here, we supplemented mice with an -3 rich diet for 3 weeks in a murine model of angiotensin-II-dependent hypertension. Also, because EPA and DHA epoxides are metabolized by soluble epoxide hydrolase (sEH), we tested the combination of an sEH inhibitor and the -3 rich diet. Our results show that -3 rich diet in combination with the sEH inhibitor lowered Ang-II, increased the blood pressure, further increased the renal levels of EPA and DHA epoxides, reduced renal markers of inflammation (ie, prostaglandins and MCP-1), downregulated an epithelial sodium channel, and upregulated angiotensin-converting enzyme-2 message and significantly modulated cyclooxygenase and lipoxygenase metabolic pathways. Overall, our findings suggest that epoxides of the -3 PUFAs contribute to lowering systolic blood pressure and attenuating inflammation in part by reduced prostaglandins and MCP-1 and by upregulation of angiotensin-converting enzyme-2 in angiotensin-II-dependent hypertension. C1 [Ulu, Arzu; Harris, Todd R.; Morisseau, Christophe; Miyabe, Christina; Dong, Hua; Liu, Jun-Yan; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Ulu, Arzu; Harris, Todd R.; Morisseau, Christophe; Miyabe, Christina; Dong, Hua; Liu, Jun-Yan; Hammock, Bruce D.] Univ Calif Davis, UC Davis Comprehens Canc Ctr, Davis, CA 95616 USA. [Inoue, Hiromi; Weiss, Robert H.] Univ Calif Davis, Sch Med, Div Nephrol, Davis, CA 95616 USA. [Schuster, Gertrud] Univ Calif Davis, Sch Med, Dept Nutr, Davis, CA 95616 USA. [Chiamvimonvat, Nipavan] Univ Calif Davis, Sch Med, Dept Internal Med, Div Cardiovasc Med, Davis, CA 95616 USA. [Iosif, Ana-Maria] Univ Calif Davis, Sch Med, Dept Publ Hlth, Div Biostat, Davis, CA 95616 USA. [Weiss, Robert H.; Chiamvimonvat, Nipavan] US Dept Vet Affairs, Med Ctr, Sacramento, CA USA. [Imig, John D.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. RP Hammock, BD (reprint author), Univ Calif Davis, Dept Entomol, 1 Shields Ave, Davis, CA 95616 USA. EM bdhammock@ucdavis.edu RI Liu, Jun-Yan/D-8890-2014; OI Imig, John/0000-0002-9668-2899 FU NIEHS [R01 ES002710]; NIEHS Superfund Research Program [P42 ES004699]; NIH [5UO1CA86402, 1R01CA135401-01A1, 1R01DK082690-01A1, HL59699, DK38226]; Medical Service of the US Department of Veterans' Affairs; NIDDK [U24 DK097154]; National Center for Advancing Translational Sciences, NIH [UL1 TR000002]; NIH T32 training grant in basic and translational cardiovascular science [T32 HL86350] FX Supported by NIEHS grant R01 ES002710 and NIEHS Superfund Research Program grant P42 ES004699; NIH grants 5UO1CA86402 (Early Detection Research Network), 1R01CA135401-01A1, and 1R01DK082690-01A1; and the Medical Service of the US Department of Veterans' Affairs (all to R. H. W.). Analytical work was partially supported by the NIH and NIDDK grant U24 DK097154. Studies and analyses performed by J. D. Imig were supported by NIH grants HL59699 and DK38226. Analyses performed by A.-M. Iosif were supported by the National Center for Advancing Translational Sciences, NIH, through grant UL1 TR000002. T. R. Harris is supported by NIH T32 training grant in basic and translational cardiovascular science (T32 HL86350). B. D. Hammock is a George and Judy Marcus senior fellow of the American Asthma Foundation, and was supported by NIEHS grant R01 ES002710 and NIEHS Superfund Research Program grant P42 ES004699. NR 65 TC 29 Z9 31 U1 3 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD SEP PY 2013 VL 62 IS 3 BP 285 EP 297 DI 10.1097/FJC.0b013e318298e460 PG 13 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 219WX UT WOS:000324543400008 PM 23676336 ER PT J AU Schmidt, P Otto, M Hechler, T Metzing, S Wolfe, J Zernikow, B AF Schmidt, Pia Otto, Michael Hechler, Tanja Metzing, Sabine Wolfe, Joanne Zernikow, Boris TI Did Increased Availability of Pediatric Palliative Care Lead to Improved Palliative Care Outcomes in Children with Cancer? SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID END-OF-LIFE; SYMPTOMS; PARENTS; PERSPECTIVES; DECISIONS; DEATH AB Background: Awareness for pediatric palliative care in children with cancer increased in the last ten years in Germany. In this study we sought to determine whether this change in awareness led to improved palliative care outcomes in children dying due to cancer. Methods: In 2005 we interviewed a cohort of 48 bereaved parents who had a lost a child to cancer approximately five years earlier (2000 cohort), and in 2010 we interviewed another cohort of 48 parents who had lost a child due to cancer approximately five years before (2005 cohort). Children of the 2000 cohort were cared for by six specialized oncology departments in North-Rhine-Westphalia (NRW), Germany, and children of the 2005 cohort by 16 specialized pediatric oncology departments in NRW, Germany. Parents of both cohorts were interviewed using the Survey of Caring for Children with Cancer (SCCC). Results: The children of both parental cohorts were similar in terms of disease characteristics and sociodemographic variables. Children suffered in a very similar manner from core symptoms such as pain and dyspnea. However, symptom treatment increased for all symptoms. In case of treatment of anxiety the increase was statistically significant (p=0.035). Location of care changed with almost three-quarters of the 2005 cohort receiving palliative home care, significantly more than in the 2000 cohort (p=0.007). Additionally, fewer children of the 2005 cohort died in the intensive care unit. Conclusion: While the location of care during the end-of-life period shifted (from hospital to home), there remains substantial work to ease the suffering in children with cancer at end of life. C1 [Schmidt, Pia; Otto, Michael; Hechler, Tanja; Zernikow, Boris] Herdecke Univ, Paediat Palliat Care Ctr, Childrens & Adolescents Hosp Datteln, Dept Childrens Pain Therapy & Paediat Palliat Car, Datteln, Germany. [Metzing, Sabine] Univ Witten Herdecke, Sch Nursing Sci, Witten, Germany. [Wolfe, Joanne] Harvard Univ, Sch Med, Pediat Palliat Care Serv, Childrens Hosp Boston,Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Schmidt, P (reprint author), Childrens & Adolescents Hosp Datteln, Dept Childrens Pain Therapy & Pediat Palliat Care, Dr Friedrich Steiner Str 5, D-45711 Datteln, Germany. EM P.Schmidt@kinderklinik-datteln.de FU German Children's Cancer Fund (Deutsche Kinderkrebshilfe e.V.) FX We would like to thank all parents who participated in our study and the participating oncology departments. This survey has been supported by the German Children's Cancer Fund (Deutsche Kinderkrebshilfe e.V.). NR 18 TC 17 Z9 19 U1 0 U2 20 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP 1 PY 2013 VL 16 IS 9 BP 1034 EP 1039 DI 10.1089/jpm.2013.0014 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 218YI UT WOS:000324468400009 PM 23901834 ER PT J AU Chittenden, EH Anderson, WG Lai, CJ O'Sullivan, P AF Chittenden, Eva H. Anderson, Wendy G. Lai, Cindy J. O'Sullivan, Patricia TI An Evaluation of Interactive Web-Based Curricula for Teaching Code Status Discussions SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HEALTH-PROFESSIONS; METAANALYSIS; CARE AB Background: Teaching resuscitation discussions to medical students and residents is time intensive and should be taught by teachers with competence in this area of clinical practice. There are plenty of data that these discussions are often inadequate, and that communication skills training, while time and faculty intensive, improves these conversations. The role of online instruction in teaching communication skills, such as resuscitation discussions, is not established. Objective: The study objective was to evaluate the effectiveness of an interactive online curriculum in teaching code status discussions to third-year medical students at one medical school. Design: In this study we block randomized third-year medical students to one of two web-based curricula versus a similar written curriculum and used standardized patient scores on a communication exercise to measure differences in performance. We used student surveys to measure student satisfaction with the curricula. Setting/subjects: Of 121 students participating in the study between April 2007 and March 2008, 88 were randomized to one of two website formats and 33 to the written curriculum. Measurements: We compared average scores on content and communication checklists between groups. Results: There were no differences between the three groups in the primary outcome of student performance. We could not analyze data on satisfaction with or completion rates for the three curricula due to poor response rates to the student surveys. Conclusions: This block randomized study of web-based curricula versus a written curriculum did not show differences in student performance in code status discussions. The optimal use of online communication training remains unclear and requires further investigation. C1 [Chittenden, Eva H.] Massachusetts Gen Hosp, Dept Gen Med & Palliat Care, Boston, MA 02115 USA. [Anderson, Wendy G.; Lai, Cindy J.; O'Sullivan, Patricia] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Chittenden, EH (reprint author), Massachusetts Gen Hosp, 55 Fruit St Founders 600, Boston, MA 02115 USA. EM echittenden@partners.org OI O'Sullivan, Patricia/0000-0002-8706-4095 NR 11 TC 1 Z9 1 U1 2 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP 1 PY 2013 VL 16 IS 9 BP 1070 EP 1073 DI 10.1089/jpm.2012.0611 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 218YI UT WOS:000324468400014 PM 23937063 ER PT J AU Auchincloss, HG Loehrer, A Hutter, MM AF Auchincloss, Hugh Glimcher Loehrer, Andrew Hutter, Matthew M. TI Reducing readmissions after complex GI surgery: targeting high-risk patients alone is inadequate SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Auchincloss, Hugh Glimcher; Loehrer, Andrew; Hutter, Matthew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S107 EP S107 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900215 ER PT J AU Chao, TE Sharma, K Hagander, L Meara, JG AF Chao, Tiffany E. Sharma, Ketan Hagander, Lars Meara, John G. TI Defining the role of surgery in global health: a systematic review of cost-effectiveness of surgery in developing countries SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Chao, Tiffany E.; Sharma, Ketan; Hagander, Lars; Meara, John G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S62 EP S62 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900115 ER PT J AU DePeralta, DK Fuchs, BC Yamada, S Fujii, T Lauwers, GY Lanuti, M Tanabe, KK AF DePeralta, Danielle K. Fuchs, Bryan C. Yamada, Suguru Fujii, Tsutomu Lauwers, Gregory Y. Lanuti, Michael Tanabe, Kenneth K. TI Epithelial growth factor receptor inhibition effectively inhibits liver fibrosis and hepatocellular carcinoma SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [DePeralta, Danielle K.; Fuchs, Bryan C.; Yamada, Suguru; Fujii, Tsutomu; Lauwers, Gregory Y.; Lanuti, Michael; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S20 EP S20 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900024 ER PT J AU Hamarneh, SR Kopecky, KE Economopoulos, KP Tao, QS Teshager, A Patel, P Malo, NS Muhammad, N Malo, MS Hodin, RA AF Hamarneh, Sulaiman R. Kopecky, Kimberly E. Economopoulos, Konstantinos P. Tao, Qingsong Teshager, Abeba Patel, Palak Malo, Nondita S. Muhammad, Nur Malo, Madhu S. Hodin, Richard A. TI The effect of intestinal alkaline phosphatase on abscess fluid-induced inflammation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Hamarneh, Sulaiman R.; Kopecky, Kimberly E.; Economopoulos, Konstantinos P.; Tao, Qingsong; Teshager, Abeba; Patel, Palak; Malo, Nondita S.; Muhammad, Nur; Malo, Madhu S.; Hodin, Richard A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S44 EP S44 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900077 ER PT J AU Jepsen, CH Johansson, PI Perner, A Sillesen, MH Alam, HB deMoya, MA AF Jepsen, Cecilie H. Johansson, Paer I. Perner, Anders Sillesen, Martin H. Alam, Hasan B. deMoya, Marc A. TI Valproic acid increases endothelial glycocalyx shedding and decreases lesion size volume in a rodent model of severe isolated traumatic brain injury SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Jepsen, Cecilie H.; Johansson, Paer I.; Perner, Anders; Sillesen, Martin H.; Alam, Hasan B.; deMoya, Marc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S32 EP S32 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900050 ER PT J AU Lee, S Yamada, Y Tonsho, M Boskovic, S Smith, RN Colvin, RB Madsen, JC Cosimi, AB Benichou, G Kawai, T AF Lee, Soyoung Yamada, Yohei Tonsho, Makoto Boskovic, Svjetlan Smith, Rex Neal Colvin, Robert B. Madsen, Joren C. Cosimi, A. Benedict Benichou, Gilles Kawai, Tatsuo TI Renal allograft tolerance can be achieved in non-human primates via delayed mixed-hematopoietic chimerism and alefacept treatment SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Lee, Soyoung; Yamada, Yohei; Tonsho, Makoto; Boskovic, Svjetlan; Smith, Rex Neal; Colvin, Robert B.; Madsen, Joren C.; Cosimi, A. Benedict; Benichou, Gilles; Kawai, Tatsuo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S142 EP S142 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900295 ER PT J AU Lee, S Aoyama, A Tonsho, M Boskovic, S Smith, RN Cosimi, AB Madsen, JC Benichou, G Kawai, T Allan, JS AF Lee, Soyoung Aoyama, Akihiro Tonsho, Makoto Boskovic, Svjetlan Smith, Rex Neal Cosimi, A. Benedict Madsen, Joren C. Benichou, Gilles Kawai, Tatsuo Allan, James S. TI Lung allograft tolerance in non-human primates following delayed donor bone marrow transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Lee, Soyoung; Aoyama, Akihiro; Tonsho, Makoto; Boskovic, Svjetlan; Smith, Rex Neal; Cosimi, A. Benedict; Madsen, Joren C.; Benichou, Gilles; Kawai, Tatsuo; Allan, James S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S142 EP S143 PG 4 WC Surgery SC Surgery GA 233OG UT WOS:000325577900296 ER PT J AU Ligorio, M Briet, JP Alfaro, E Sabbatino, F Wargo, J Vikram, D Fernandez-del Castillo, C Goff, S Lillemoe, KD Ferrone, CR AF Ligorio, Matteo Briet, Jan Paul Alfaro, Eduardo Sabbatino, Francesco Wargo, Jennifer Vikram, Deshpande Fernandez-del Castillo, Carlos Goff, Stephanie Lillemoe, Keith D. Ferrone, Cristina R. TI PHH3 immunostaining: a novel prognostic biomarker in pancreatic neuroendocrine tumors SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Ligorio, Matteo; Briet, Jan Paul; Alfaro, Eduardo; Sabbatino, Francesco; Wargo, Jennifer; Vikram, Deshpande; Fernandez-del Castillo, Carlos; Goff, Stephanie; Lillemoe, Keith D.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S129 EP S129 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900263 ER PT J AU Loehrer, AP Auchincloss, HG Song, ZR Hutter, MM AF Loehrer, Andrew P. Auchincloss, Hugh G. Song, Zirui Hutter, Matthew M. TI Massachusetts health care reform is associated with reduced disparities in the management of acute cholecystitis SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Loehrer, Andrew P.; Auchincloss, Hugh G.; Song, Zirui; Hutter, Matthew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S101 EP S102 PG 4 WC Surgery SC Surgery GA 233OG UT WOS:000325577900202 ER PT J AU Moaven, O Economopoulos, KP Alam, SN Muhammad, N Kaliannan, K Ray, M Mohamed, MMR Moss, AK Malo, MS Hodin, RA AF Moaven, Omeed Economopoulos, Konstantinos P. Alam, Sayeda N. Muhammad, Nur Kaliannan, Kanakaraju Ray, Madhury Mohamed, Mussa M. Rafat Moss, Angela K. Malo, Madhu S. Hodin, Richard A. TI Intestinal alkaline phosphatase is an endogenous regulator of host microbiota SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Moaven, Omeed; Economopoulos, Konstantinos P.; Alam, Sayeda N.; Muhammad, Nur; Kaliannan, Kanakaraju; Ray, Madhury; Mohamed, Mussa M. Rafat; Moss, Angela K.; Malo, Madhu S.; Hodin, Richard A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI kaliannan, kanakaraju/P-9094-2014 NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S14 EP S14 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900007 ER PT J AU Sabbatino, F Wang, YY Poudel, R Ligorio, M Favoino, E Wang, XH Wargo, J Ferrone, S Lillemoe, KD Ferrone, CR AF Sabbatino, Francesco Wang, Yangyang Poudel, Ravin Ligorio, Matteo Favoino, Elvira Wang, Xinhui Wargo, Jennifer Ferrone, Soldano Lillemoe, Keith D. Ferrone, Cristina R. TI Novel combinatorial therapy for pancreatic adenocarcinoma SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Sabbatino, Francesco; Wang, Yangyang; Poudel, Ravin; Ligorio, Matteo; Favoino, Elvira; Wang, Xinhui; Wargo, Jennifer; Ferrone, Soldano; Lillemoe, Keith D.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Favoino, Elvira/D-4804-2014; OI Sabbatino, Francesco/0000-0001-6431-8278 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S137 EP S137 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900282 ER PT J AU Sadeghipour, H Torabi, R Leonard, D Gottschall, J Sachs, DH Cetrulo, CL Moore, FD AF Sadeghipour, Hamed Torabi, Radbeh Leonard, David Gottschall, James Sachs, David H. Cetrulo, Curtis L., Jr. Moore, Francis D. TI Effect of nonmuscle myosin-derived peptide on cutaneous burn wound injury SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 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 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S93 EP S93 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900184 ER PT J AU Schmidt, B Deperalta, DK Wei, L Hoshida, Y Tanabe, KK Fuchs, BC AF Schmidt, Benjamin Deperalta, Danielle K. Wei, Lan Hoshida, Yujin Tanabe, Kenneth K. Fuchs, Bryan C. TI Molecular subclasses of human hepatocellular carcinoma predict sensitivity to fibroblast growth factor receptor inhibition SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Schmidt, Benjamin; Deperalta, Danielle K.; Wei, Lan; Hoshida, Yujin; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S132 EP S132 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900271 ER PT J AU Sillesen, M Johansson, PI Rasmussen, LS Jin, G Imam, A Hwabejire, JO Jepsen, CH Velmahos, G deMoya, MA Alam, HB AF Sillesen, Martin Johansson, Paer I. Rasmussen, Lars S. Jin, Guang Imam, Ayesha Hwabejire, John O. Jepsen, Cecilie H. Velmahos, George deMoya, Marc A. Alam, Hasan B. TI Fresh frozen plasma resuscitation attenuates platelet dysfunction and endothelial activation in a large animal model of poly-trauma SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Sillesen, Martin; Johansson, Paer I.; Rasmussen, Lars S.; Jin, Guang; Imam, Ayesha; Hwabejire, John O.; Jepsen, Cecilie H.; Velmahos, George; deMoya, Marc A.; Alam, Hasan B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S50 EP S51 PG 4 WC Surgery SC Surgery GA 233OG UT WOS:000325577900090 ER PT J AU Sillesen, M Johansson, PI Rasmussen, LS Jin, G Jepsen, CH Imam, A Hwabejire, JO Velmahos, G deMoya, MA Alam, HB AF Sillesen, Martin Johansson, Per I. Rasmussen, Lars S. Jin, Guang Jepsen, Cecilie H. Imam, Ayesha Hwabejire, John O. Velmahos, George deMoya, Marc A. Alam, Hasan B. TI Valproic acid attenuates platelet dysfunction, endothelial glycocalyx shedding and protein C activation in a porcine model of traumatic brain injury and shock SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Sillesen, Martin; Johansson, Per I.; Rasmussen, Lars S.; Jin, Guang; Jepsen, Cecilie H.; Imam, Ayesha; Hwabejire, John O.; Velmahos, George; deMoya, Marc A.; Alam, Hasan B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S51 EP S51 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900091 ER PT J AU Zhao, T Li, YQ Liu, BL Mazitschek, R Duan, XZ Velmahos, GC Alam, HB AF Zhao, Ting Li, Yongqing Liu, Baoling Mazitschek, Ralph Duan, Xiuzhen Velmahos, George C. Alam, Hasan B. TI Selective inhibition of histone deacetylase 6 attenuates inflammation and improves long-term survival in a lethal septic model SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg C1 [Zhao, Ting; Li, Yongqing; Liu, Baoling; Mazitschek, Ralph; Duan, Xiuzhen; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 SU S BP S45 EP S45 PG 1 WC Surgery SC Surgery GA 233OG UT WOS:000325577900079 ER PT J AU Choi, SY Chacon-Heszele, MF Huang, LW McKenna, S Wilson, FP Zuo, XF Lipschutz, JH AF Choi, Soo Young Chacon-Heszele, Maria F. Huang, Liwei McKenna, Sarah Wilson, F. Perry Zuo, Xiaofeng Lipschutz, Joshua H. TI Cdc42 Deficiency Causes Ciliary Abnormalities and Cystic Kidneys SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; RAC1 SMALL GTPASES; CELL-POLARITY; EPITHELIAL-CELLS; PRIMARY CILIOGENESIS; SPINDLE ORIENTATION; KUPFFERS VESICLE; PRIMARY CILIUM; KIF3A SUBUNIT; KINESIN-II AB Ciliogenesis and cystogenesis require the exocyst, a conserved eight-protein trafficking complex that traffics ciliary proteins. In culture, the small GTPase Cdc42 co-localizes with the exocyst at primary cilia and interacts with the exocyst component Sec10. The role of Cdc42 in vivo, however, is not well understood. Here, knockdown of cdc42 in zebrafish produced a phenotype similar to sec10 knockdown, including tail curvature, glomerular expansion, and mitogen-activated protein kinase (MAPK) activation, suggesting that cdc42 and sec10 cooperate in ciliogenesis. In addition, cdc42 knockdown led to hydrocephalus and loss of photoreceptor cilia. Furthermore, there was a synergistic genetic interaction between zebrafish cdc42 and sec10, suggesting that cdc42 and sec10 function in the same pathway. Mice lacking Cdc42 specifically in kidney tubular epithelial cells died of renal failure within weeks of birth. Histology revealed cystogenesis in distal tubules and collecting ducts, decreased ciliogenesis in cyst cells, increased tubular cell proliferation, increased apoptosis, increased fibrosis, and led to MAPK activation, all of which are features of polycystic kidney disease, especially nephronophthisis. Taken together, these results suggest that Cdc42 localizes the exocyst to primary cilia, whereupon the exocyst targets and docks vesicles carrying ciliary proteins. Abnormalities in this pathway result in deranged ciliogenesis and polycystic kidney disease. C1 [Choi, Soo Young; Chacon-Heszele, Maria F.; Huang, Liwei; McKenna, Sarah; Wilson, F. Perry; Zuo, Xiaofeng; Lipschutz, Joshua H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Wilson, F. Perry] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lipschutz, Joshua H.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Lipschutz, JH (reprint author), Room 405C,Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. EM jhlipsch@mail.med.upenn.edu FU Department of Veterans Affairs [1L01BX00820]; National Institutes of Health [DK069909, DK047757, DK093625]; Satellite Healthcare; NephHope Postdoctoral Fellowship; University of Pennsylvania Translational Medicine Institute FX This work was supported in part by grants from the Department of Veterans Affairs (VA Merit Award 1L01BX00820 to J.H.L.), National Institutes of Health (DK069909 and DK047757 to J.H.L., and DK093625 to L. H.), Satellite Healthcare (Norman S. Coplon Extramural Research Grant to J.H.L), a NephHope Postdoctoral Fellowship (to M. F. C. H.), and the University of Pennsylvania Translational Medicine Institute (pilot grant to J.H.L). NR 63 TC 20 Z9 20 U1 0 U2 7 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2013 VL 24 IS 9 BP 1435 EP 1450 DI 10.1681/ASN.2012121236 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA 227EO UT WOS:000325092900015 PM 23766535 ER PT J AU O'Seaghdha, CM Hwang, SJ Ho, JE Vasan, RS Levy, D Fox, CS AF O'Seaghdha, Conall M. Hwang, Shih-Jen Ho, Jennifer E. Vasan, Ramachandran S. Levy, Daniel Fox, Caroline S. TI Elevated Galectin-3 Precedes the Development of CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; PLASMA TOTAL HOMOCYSTEINE; ALL-CAUSE MORTALITY; HEART-FAILURE; RENAL-INSUFFICIENCY; DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; BLOOD-PRESSURE AB Galectin-3, a profibrotic mediator, is linked to the development of renal fibrosis in animal models and inversely correlates with GFR in humans, but whether galectin-3 predicts incident kidney disease is unknown. Here, we assessed renal outcomes for 2450 Framingham Offspring participants who attended examination 6 (1995-1998) and had follow-up data at examination 8 (2005-2008). Renal outcomes of interest included rapid decline in renal function (3 ml/min per 1.73 m(2) per year decline in estimated GFR [eGFR]), CKD (eGFR < 60 ml/min per 1.73 m(2)), and albuminuria (albumin-to-creatinine ratio 17 mg/g in men or 25 mg/g in women). We used multivariable logistic regression models to evaluate associations between galectin-3 with incident renal outcomes at examination 8. During a mean follow-up of 10.1 years, GFR declined rapidly in 241 (9.2%) participants, incident CKD developed in 277 (11.3%), and albuminuria developed in 194 (10.1%). Higher plasma levels of galectin-3 were associated with rapid decline in eGFR (per 1-SD log-galectin-3; adjusted odds ratio [OR], 1.49; 95% confidence interval [CI], 1.28 to 1.73]) and a higher risk of incident CKD (OR, 1.47; 95% CI, 1.27 to 1.71), but not with the risk of incident albuminuria. The addition of galectin-3 to clinical predictors improved the C-statistic (0.837-0.845; P=0.02) but did not reach predefined thresholds for clinically significant improvements to risk prediction based on reclassification indices. In conclusion, elevated levels of plasma galectin-3 are associated with increased risks of rapid GFR decline and of incident CKD in the community, which calls for further study in higher-risk groups. C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Ho, Jennifer E.; Vasan, Ramachandran S.; Levy, Daniel; Fox, Caroline S.] NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA. [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Ho, Jennifer E.; Vasan, Ramachandran S.; Levy, Daniel; Fox, Caroline S.] Ctr Populat Studies, Bethesda, MD USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [Ho, Jennifer E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [O'Seaghdha, Conall M.] Beaumont Hosp, Div Nephrol & Transplantat, Dublin 9, Ireland. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Cardiol & Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Epidemiol Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; American Heart Association FX The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute (N01-HC-25195). J.E.H. is supported by an American Heart Association Clinical Research Program award. NR 69 TC 42 Z9 46 U1 0 U2 11 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2013 VL 24 IS 9 BP 1470 EP 1477 DI 10.1681/ASN.2012090909 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 227EO UT WOS:000325092900018 PM 23766533 ER PT J AU Woodruff, MC Herndon, CN Heesters, BA Carroll, MC AF Woodruff, Matthew C. Herndon, Caroline N. Heesters, B. A. Carroll, Michael C. TI Contextual Analysis of Immunological Response through Whole- Organ Fluorescent Imaging SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID T-CELL-ACTIVATION; LYMPH-NODES; DENDRITIC CELLS; L-SELECTIN; IN-VIVO; MICROSCOPY; ANTIGEN; DYNAMICS; ORGANIZATION; GROWTH AB Background: As fluorescent microscopy has developed, significant insights have been gained into the establishment of immune response within secondary lymphoid organs, particularly in draining lymph nodes. While established techniques such as confocal imaging and intravital multi-photon microscopy have proven invaluable, they provide limited insight into the architectural and structural context in which these responses occur. To interrogate the role of the lymph node environment in immune response effectively, a new set of imaging tools taking into account broader architectural context must be implemented into emerging immunological questions. Methods and Results: Using two different methods of whole-organ imaging, optical clearing and three-dimensional reconstruction of serially sectioned lymph nodes, fluorescent representations of whole lymph nodes can be acquired at cellular resolution. Using freely available post-processing tools, images of unlimited size and depth can be assembled into cohesive, contextual snapshots of immunological response. Through the implementation of robust iterative analysis techniques, these highly complex three-dimensional images can be objectified into sortable object data sets. These data can then be used to interrogate complex questions at the cellular level within the broader context of lymph node biology. Conclusions: By combining existing imaging technology with complex methods of sample preparation and capture, we have developed efficient systems for contextualizing immunological phenomena within lymphatic architecture. In combination with robust approaches to image analysis, these advances provide a path to integrating scientific understanding of basic lymphatic biology into the complex nature of immunological response. C1 [Woodruff, Matthew C.] Harvard Univ, Sch Med, Grad Program Immunol, Boston, MA 02115 USA. [Woodruff, Matthew C.; Herndon, Caroline N.; Heesters, B. A.; Carroll, Michael C.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Heesters, B. A.] Univ Med Ctr Utrecht, Utrecht, Netherlands. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, 200 Longwood Ave,Room 251, Boston, MA 02115 USA. EM Michael.Carroll@childrens.harvard.edu FU NIH-NIAID [1 P01 AI078897, 5 P01 AI07889705]; NIH [T32 AI007498]; American Lung Association [RT-224269-N] FX This study is financially supported by NIH-NIAID (1 P01 AI078897 to M. C. C., 5 P01 AI07889705 to U. H. v. A.), NIH T32 Training Grant in Transplantation (T32 AI007498 to M. C. W.), and the American Lung Association (RT-224269-N to C. H.). Drs. Herndon and Carrol and M. C. Woodruff and B. A. Heesters disclosed on conflicts of interest or financial ties. NR 32 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 EI 1557-8585 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PD SEP 1 PY 2013 VL 11 IS 3 SI SI BP 121 EP 127 DI 10.1089/lrb.2013.0011 PG 7 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 219AY UT WOS:000324477300004 PM 24044754 ER PT J AU Liao, S Padera, TP AF Liao, Shan Padera, Timothy P. TI Lymphatic Function and Immune Regulation in Health and Disease SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID HIGH ENDOTHELIAL VENULES; SUBCAPSULAR SINUS MACROPHAGES; GROWTH-FACTOR-C; SENTINEL-NODE BIOPSY; L-SELECTIN LIGANDS; DENDRITIC CELLS; NITRIC-OXIDE; STEADY-STATE; IN-VIVO; CANCER-CELLS C1 Harvard Univ, Sch Med, Dept Radiat Oncol, EL Steele Lab, Boston, MA USA. [Padera, Timothy P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Padera, TP (reprint author), Massachusetts Gen Hosp, Radiat Oncol Cox 7,100 Blossom St, Boston, MA 02114 USA. EM tpadera@steele.mgh.harvard.edu OI Padera, Timothy/0000-0002-3453-9384 FU NIH [R00CA137167, DP2OD008780, R21AI097745, K99HL111343]; NCI Federal Share/Proton Beam Income; Charles King Trust Fellowship FX The authors are supported by NIH R00CA137167, NIH DP2OD008780, NIH R21AI097745 and NCI Federal Share/Proton Beam Income (TPP), Charles King Trust Fellowship and NIH K99HL111343 (SL). NR 116 TC 12 Z9 12 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 EI 1557-8585 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PD SEP 1 PY 2013 VL 11 IS 3 SI SI BP 136 EP 143 DI 10.1089/lrb.2013.0012 PG 8 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 219AY UT WOS:000324477300006 PM 24024577 ER PT J AU Cheng, C Gao, XQ Feng, BM Sheen, J Shan, LB He, P AF Cheng, Cheng Gao, Xiquan Feng, Baomin Sheen, Jen Shan, Libo He, Ping TI Plant immune response to pathogens differs with changing temperatures SO NATURE COMMUNICATIONS LA English DT Article ID INNATE IMMUNITY; NUCLEAR ACCUMULATION; DISEASE RESISTANCE; EFFECTOR AVRRPT2; PLASMA-MEMBRANE; RECEPTOR FLS2; ARABIDOPSIS; DEFENSE; KINASE; RECOGNITION AB Temperature fluctuation is a key determinant for microbial invasion and host evasion. In contrast to mammals that maintain constant body temperature, plant temperature oscillates on a daily basis. It remains elusive how plants operate inducible defenses in response to temperature fluctuation. Here we report that ambient temperature changes lead to pronounced shifts of the following two distinct plant immune responses: pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). Plants preferentially activate ETI signaling at relatively low temperatures (10-23 degrees C), whereas they switch to PTI signaling at moderately elevated temperatures (23-32 degrees C). The Arabidopsis arp6 and hta9hta11 mutants, phenocopying plants grown at elevated temperatures, exhibit enhanced PTI and yet reduced ETI responses. As the secretion of bacterial effectors favours low temperatures, whereas bacteria multiply vigorously at elevated temperatures accompanied with increased microbe-associated molecular pattern production, our findings suggest that temperature oscillation might have driven dynamic co-evolution of distinct plant immune signaling responding to pathogen physiological changes. C1 [Cheng, Cheng; Feng, Baomin; He, Ping] Texas A&M Univ, Dept Biochem & Biophys, Inst Plant Genom & Biotechnol, College Stn, TX 77843 USA. [Gao, Xiquan; Shan, Libo] Texas A&M Univ, Dept Plant Pathol & Microbiol, Inst Plant Genom & Biotechnol, College Stn, TX 77843 USA. [Gao, Xiquan] Nanjing Agr Univ, Cytogenet Inst, Natl Key Lab Crop Genet & Germplasm Enhancement, Nanjing 210095, Jiangsu, Peoples R China. [Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP He, P (reprint author), Texas A&M Univ, Dept Biochem & Biophys, Inst Plant Genom & Biotechnol, College Stn, TX 77843 USA. EM pinghe@tamu.edu FU NIH [R01 GM70567, 1R01GM097247, R01GM092893]; NSF [IOS-1030250]; Robert A. Welch Foundation [A-1795]; USDA National Institute of Food and Agriculture [2012-67013-19433] FX We thank Dr. B. Staskawicz for DEX-avrRpt2 and pRPS2::RPS2-HA transgenic plant seeds, Dr. D. Mackey for DEX-avrRpm1-HA (rpm1) transgenic plant seeds, Dr. T. Nurnberger for HrpZ and NPP1 clones, Dr P. Wigge for arp6-10 and hta9hta11 mutant seeds and Dr. G. Coaker for a-RIN4 antibody. This work was supported by NIH (R01 GM70567) to J.S., NSF (IOS-1030250), NIH (1R01GM097247) and The Robert A. Welch Foundation (A-1795) to L.S., NIH (R01GM092893) to P.H., and USDA National Institute of Food and Agriculture (2012-67013-19433) to L.S. and P.H. NR 46 TC 21 Z9 24 U1 4 U2 69 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD SEP PY 2013 VL 4 AR 2530 DI 10.1038/ncomms3530 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233AQ UT WOS:000325536900001 PM 24067909 ER PT J AU Park, HJ Bonmassar, G Kaltenbach, JA Machado, AG Manzoor, NF Gale, JT AF Park, Hyun-Joo Bonmassar, Giorgio Kaltenbach, James A. Machado, Andre G. Manzoor, Nauman F. Gale, John T. TI Activation of the central nervous system induced by micro-magnetic stimulation SO NATURE COMMUNICATIONS LA English DT Article ID DEEP BRAIN-STIMULATION; DORSAL COCHLEAR NUCLEUS; ELECTRICAL-STIMULATION; COGNITIVE NEUROSCIENCE; PARKINSON-DISEASE; THALAMOTOMY; RECOVERY; SURGERY; TISSUE AB Electrical and transcranial magnetic stimulations have proven to be therapeutically beneficial for patients suffering from neurological disorders. Moreover, these stimulation technologies have provided invaluable tools for investigating nervous system functions. Despite this success, these technologies have technical and practical limitations impeding the maximization of their full clinical and preclinical potential. Recently, micro-magnetic stimulation, which may offer advantages over electrical and transcranial magnetic stimulation, has proven effective in activating the neuronal circuitry of the retina in vitro. Here we demonstrate that this technology is also capable of activating neuronal circuitry on a systems level using an in vivo preparation. Specifically, the application of micro-magnetic fields to the dorsal cochlear nucleus activates inferior colliculus neurons. Additionally, we demonstrate the efficacy and characteristics of activation using different magnetic stimulation parameters. These findings provide a rationale for further exploration of micro-magnetic stimulation as a prospective tool for clinical and preclinical applications. C1 [Park, Hyun-Joo; Kaltenbach, James A.; Machado, Andre G.; Manzoor, Nauman F.; Gale, John T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44195 USA. [Bonmassar, Giorgio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr, Charlestown, MA 02129 USA. [Kaltenbach, James A.] Cleveland Clin, Head & Neck Inst, Cleveland, OH 44195 USA. [Machado, Andre G.; Gale, John T.] Cleveland Clin, Ctr Neurol Restorat, Cleveland, OH 44195 USA. RP Gale, JT (reprint author), Cleveland Clin, Dept Neurosci, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM galej@ccf.org RI Machado, Andre/B-7572-2014 OI Machado, Andre/0000-0002-8132-5610 FU National Eye Institute [1R21EY020961-01]; NIH [R01 DC009097]; National Center for Research Resources (NCRR) [P41-RR14075]; MIND Institute FX Funding for this project was provided by the National Eye Institute (1R21EY020961-01), NIH grant R01 DC009097, the National Center for Research Resources (NCRR) (P41-RR14075), and by the MIND Institute. NR 42 TC 9 Z9 9 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD SEP PY 2013 VL 4 AR 2463 DI 10.1038/ncomms3463 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232ZO UT WOS:000325533900010 PM 24030203 ER PT J AU Polley, DB Thompson, JH Guo, W AF Polley, Daniel B. Thompson, John H. Guo, Wei TI Brief hearing loss disrupts binaural integration during two early critical periods of auditory cortex development SO NATURE COMMUNICATIONS LA English DT Article ID INFERIOR COLLICULUS; OTITIS-MEDIA; VISUAL-CORTEX; RESPONSE PROPERTIES; SENSITIVE PERIODS; LEVEL DIFFERENCES; CORTICAL-NEURONS; SUPERIOR OLIVE; SOUND LOCATION; BRAIN-STEM AB Early binaural experience can recalibrate central auditory circuits that support spatial hearing. However, it is not known how binaural integration matures shortly after hearing onset or whether various developmental stages are differentially impacted by disruptions of normal binaural experience. Here we induce a brief, reversible unilateral conductive hearing loss (CHL) at several experimentally determined milestones in mouse primary auditory cortex (A1) development and characterize its effects similar to 1 week after normal hearing is restored. We find that CHL shapes A1 binaural selectivity during two early critical periods. CHL before P16 disrupts the normal coregistration of interaural frequency tuning, whereas CHL on P16, but not before or after, disrupts interaural level difference sensitivity contained in long-latency spikes. These data highlight an evolving plasticity in the developing auditory cortex that may relate to the aetiology of amblyaudia, a binaural hearing impairment associated with bouts of otitis media during human infancy. C1 [Polley, Daniel B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Polley, Daniel B.; Thompson, John H.; Guo, Wei] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Polley, Daniel B.; Guo, Wei] Boston Univ, Ctr Computat Neurosci & Neural Technol, Boston, MA 02215 USA. RP Polley, DB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. EM daniel_polley@meei.harvard.edu OI Polley, Daniel/0000-0002-5120-2409 FU National Institutes of Health [R01 DC009836, P30 DC5029]; Howard Hughes Medical Institute International Student Research Fellowship FX This work was supported by the National Institutes of Health Grants R01 DC009836 (D.B.P.), P30 DC5029 and a Howard Hughes Medical Institute International Student Research Fellowship (W.G.). NR 70 TC 26 Z9 26 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD SEP PY 2013 VL 4 AR 2547 DI 10.1038/ncomms3547 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233BC UT WOS:000325538200001 PM 24077484 ER PT J AU Zhao, JH Zhou, HJ Liu, YY AF Zhao, Jin-Hua Zhou, Hai-Jun Liu, Yang-Yu TI Inducing effect on the percolation transition in complex networks SO NATURE COMMUNICATIONS LA English DT Article ID SCALE-FREE NETWORKS; RANDOM GRAPHS; INTERDEPENDENT NETWORKS; EXPLOSIVE PERCOLATION; MODEL; CASCADES; CORE; LOAD AB Percolation theory concerns the emergence of connected clusters that percolate through a networked system. Previous studies ignored the effect that a node outside the percolating cluster may actively induce its inside neighbours to exit the percolating cluster. Here we study this inducing effect on the classical site percolation and K-core percolation, showing that the inducing effect always causes a discontinuous percolation transition. We precisely predict the percolation threshold and core size for uncorrelated random networks with arbitrary degree distributions. For low-dimensional lattices the percolation threshold fluctuates considerably over realizations, yet we can still predict the core size once the percolation occurs. The core sizes of real-world networks can also be well predicted using degree distribution as the only input. Our work therefore provides a theoretical framework for quantitatively understanding discontinuous breakdown phenomena in various complex systems. C1 [Zhao, Jin-Hua; Zhou, Hai-Jun] Chinese Acad Sci, Inst Theoret Phys, State Key Lab Theoret Phys, Beijing 100190, Peoples R China. [Liu, Yang-Yu] Northeastern Univ, Ctr Complex Network Res & Dept Phys, Boston, MA 02115 USA. [Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Zhou, HJ (reprint author), Chinese Acad Sci, Inst Theoret Phys, State Key Lab Theoret Phys, Zhong Guan Cun East Rd 55, Beijing 100190, Peoples R China. EM zhouhj@itp.ac.cn RI Zhou, Hai-Jun/A-9804-2009; Zhao, Jin-Hua/I-7437-2016; OI Zhou, Hai-Jun/0000-0003-4228-4438; Zhao, Jin-Hua/0000-0002-6234-5579; Liu, Yang-Yu/0000-0003-2728-4907 FU National Basic Research Program of China [2013CB932804]; Knowledge Innovation Program of Chinese Academy of Sciences [KJCX2-EW-J02]; National Science Foundation of China [11121403, 11225526]; Network Science Collaborative Technology Alliance [W911NF-09-2-0053]; Defense Advanced Research Projects Agency [11645021]; Defense Threat Reduction Agency-WMD award [HDTRA1-08-1-0027, HDTRA1-10-1-0100] FX J.-H.Z. and H.-J.Z. thank Prof. Zhong-Can Ou-Yang for support and Hong-Bo Jin for technical assistance on computer simulation. J.-H.Z. and H.-J.Z. were supported by the National Basic Research Program of China (No. 2013CB932804), the Knowledge Innovation Program of Chinese Academy of Sciences (No. KJCX2-EW-J02) and the National Science Foundation of China (grant Nos. 11121403, 11225526). Y.-Y.L. was supported by the Network Science Collaborative Technology Alliance under Agreement Number W911NF-09-2-0053, the Defense Advanced Research Projects Agency under Agreement Number 11645021, the Defense Threat Reduction Agency-WMD award numbers HDTRA1-08-1-0027 and HDTRA1-10-1-0100, and the generous support of Lockheed Martin. NR 43 TC 16 Z9 16 U1 6 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD SEP PY 2013 VL 4 AR 2412 DI 10.1038/ncomms3412 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232ZM UT WOS:000325533700009 PM 24013476 ER PT J AU Pan, Q Delahanty, LM Jablonski, KA Knowler, WC Kahn, SE Florez, JC Franks, PW AF Pan, Qing Delahanty, Linda M. Jablonski, Kathleen A. Knowler, William C. Kahn, Steven E. Florez, Jose C. Franks, Paul W. CA Diabet Prevention Program Res Grp TI Variation at the Melanocortin 4 Receptor Gene and Response to Weight-Loss Interventions in the Diabetes Prevention Program SO OBESITY LA English DT Article ID LIFE-STYLE INTERVENTION; BODY-MASS INDEX; COMMON VARIANTS; PIMA-INDIANS; MC4R GENE; BASE-LINE; OBESITY; METFORMIN; COHORT; RISK AB Objective: To assess associations and genotype x treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits. Design and Methods: Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment. Results: The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all P-interaction < 0.05). Conclusion: This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions. C1 [Pan, Qing; Jablonski, Kathleen A.] George Washington Univ, Biostat Ctr, Dept Biostat & Epidemiol, Dept Stat, Rockville, MD USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Diabet Res Ctr, MGH Diabet Ctr, Dept Med, Boston, MA 02114 USA. [Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Franks, Paul W.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. RP Franks, PW (reprint author), Lund Univ, Dept Clin Sci, Malmo, Sweden. EM paul.franks@med.lu.se OI Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; Department of Veterans Affairs; American Diabetes Association; McKesson BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson Foundation; Novo Nordisk; Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Diabetes Association; [R01 DK072041-02] FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study; collection, management, analysis, and interpretation of the data (U01 DK048489). The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health, the Department of Veterans Affairs, and the American Diabetes Association. This research was also supported, in part, by the intramural research program of the NIDDK. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. This work was funded by R01 DK072041-02 to JCF and KAJ (PWF and WCK are unpaid co-investigators). PWF was supported by grants from Novo Nordisk, the Swedish Research Council, the Swedish Heart-Lung Foundation and the Swedish Diabetes Association. SEK is supported in part by the Department of Veterans Affairs. JCF has received consulting honoraria from Novartis, Lilly and Pfizer. No other potential conflict of interest is declared by any author. NR 28 TC 11 Z9 11 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD SEP PY 2013 VL 21 IS 9 BP E520 EP E526 DI 10.1002/oby.20459 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 231ON UT WOS:000325426600026 PM 23512951 ER PT J AU Arterburn, D Livingston, EH Olsen, MK Smith, VA Kavee, AL Kahwati, LC Henderson, WG Maciejewski, ML AF Arterburn, David Livingston, Edward H. Olsen, Maren K. Smith, Valerie A. Kavee, Andrew L. Kahwati, Leila C. Henderson, William G. Maciejewski, Matthew L. TI Predictors of initial weight loss after gastric bypass surgery in twelve veterans affairs medical centers SO OBESITY RESEARCH & CLINICAL PRACTICE LA English DT Article DE Gastric bypass surgery ID LONG-TERM MORTALITY; BARIATRIC SURGERY; SURGICAL CARE; OUTCOMES; QUALITY; IMPACT; IMPROVEMENT; OPERATIONS; FACILITIES; PROGRAM AB The objective of this study was to identify determinants of significant weight loss one year after gastric bypass surgery among United States veterans. Using data from the Veterans Affairs (VA) Surgical Quality Improvement Program, we identified 516 veterans who had gastric bypass surgery (24% laparoscopic) in one of twelve VA bariatric centers in 2000-2006 and one or more postoperative weight measures. The probability of losing 30% or more of baseline weight at one year was estimated via logistic regression, examining the following potential predictor variables: age, gender, race, marital status, body mass index (BMI), American Society of Anesthesiologists class, comorbidity burden, smoking status, diabetes medications taken and surgical procedure (open or laparoscopic). The 516 cases had a mean BMI of 49 kg/m(2), mean age of 51.5 years, 74% were male, 77% were Caucasian, and 55% were married. The predicted mean weight loss was 76 (95% CI: 73-79) pounds (22%) at six months and 109 (95% CI: 104-114) pounds (32%) at one-year. Based upon estimated individual trajectories of 370 patients with adequate follow-up data, 58% of the sample lost 30% or more of their baseline weight at one year; and <1% lost <10% of their baseline weight at 1 year. In the logistic regression, patients were more likely to Lose 30% or more of their baseline weight if they were female (odds ratio (OR) = 2.5, p < 0.01) or Caucasian (OR = 2.3, p < 0.01). We conclude that gastric bypass surgery yields significant weight loss for most patients in Veterans Affairs Medical Centers, but is particularly effective for female and Caucasian patients. (C) 2012 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. C1 [Arterburn, David] Grp Hlth Res Inst, Seattle, WA USA. [Arterburn, David] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Livingston, Edward H.] Univ Texas SW Med Ctr Dallas, Div Gastrointestinal & Endocrine Surg, Dallas, TX 75390 USA. [Livingston, Edward H.] Vet Adm North Texas Hlth Care Syst, Dallas, TX USA. [Livingston, Edward H.] Univ Texas Arlington, Dept Biomed Engn, Arlington, TX 76019 USA. [Olsen, Maren K.; Smith, Valerie A.; Kavee, Andrew L.; Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Olsen, Maren K.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27706 USA. [Henderson, William G.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Henderson, William G.] Univ Colorado, Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Henderson, William G.] Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Aurora, CO USA. [Maciejewski, Matthew L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC 27706 USA. RP Maciejewski, ML (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care 152, 411 West Chapel Hill St,Suite 600, Durham, NC 27705 USA. EM arterburn.d@ghc.org; matthew.maciejewski@va.gov FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 05-201, SHP 08-137]; Takeda Pharmaceuticals; Novartis; Surgical Review Corporation FX This work was supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs (IIR 05-201, SHP 08-137). The authors also would like to acknowledge the VA Surgical Quality Data Use Group (SQDUG) for its role as scientific advisors and for the critical review of data use and analysis presented in this manuscript. Dr. Arterburn was formerly with the Cincinnati VA and Dr. Livingston was formerly with the Dallas VA. Dr. Maciejewski has received consultation funds from Takeda Pharmaceuticals, Novartis and the Surgical Review Corporation, and owns stock in Amgen. The views expressed are those of the authors and do not reflect the views of the Department of Veterans Affairs, the United States Government, Duke University, the University of Texas Southwestern Medical Center, the University of Texas, the University of Colorado, the Group Health Research Institute, or the University of Washington. NR 28 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1871-403X EI 1878-0318 J9 OBES RES CLIN PRACT JI Obes. Res. Clin. Pract. PD SEP-OCT PY 2013 VL 7 IS 5 BP E367 EP E376 DI 10.1016/j.orcp.2012.02.009 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 232EU UT WOS:000325475100006 PM 24304479 ER PT J AU Grove, AS Weber, AL AF Grove, Arthur S., Jr. Weber, Alfred L. TI Orbital Pseudotumor-Historical Origin and Modern Relevance SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Purpose: To translate the original article from German in order to understand what the author was describing when Birch-Hirschfeld first used the diagnosis of orbital pseudotumor in 1905. To study why he used that diagnosis in the context of medical care and orbital diagnosis at the beginning of the twentieth century. Then to determine whether the term still has scientific relevance today. Design: Perspective. Results: In 1905, orbital pseudotumor was used as a term to describe clinical situations in which modern scientific methods would have provided more accurate and specific diagnoses. The original reasons for its use were a consequence of the limitations of medical care at the juncture of the nineteenth and twentieth centuries and the nature of orbital diseases more than a century ago. Conclusions: Orbital pseudotumor should no longer be used as a diagnosis because it is not based on current scientific knowledge. It is not specific and it hinders the application of diagnoses that are more useful in patient management. C1 [Grove, Arthur S., Jr.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol Orbital & Ophthalm Reconstruct Su, Boston, MA USA. [Weber, Alfred L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Grove, AS (reprint author), 50 Staniford St,3rd Floor, Boston, MA 02114 USA. EM arthurgrove@comcast.net NR 11 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP PY 2013 VL 29 IS 5 BP 341 EP 346 DI 10.1097/IOP.0b013e31828dea74 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 220NT UT WOS:000324592000014 PM 23584450 ER PT J AU De Castro, DK Santiago, YMB Cunningham, M Gray, ST Metson, R Fay, A AF De Castro, Dawn K. Santiago, Yvette Marie B. Cunningham, Michael Gray, Stacey T. Metson, Ralph Fay, Aaron TI A Modified Lacrimal Sac Implant for High-Risk Dacryocystorhinostomy SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID FRONTAL-SINUS SURGERY; WEGENERS-GRANULOMATOSIS; ENDONASAL DACRYOCYSTORHINOSTOMY; DRAINAGE SURGERY; SARCOIDOSIS; STENT; LONG; RECONSTRUCTION; OBSTRUCTION; DISEASE AB Purpose: The reported 5% of patients with nasolacrimal duct obstruction who fail dacryocystorhinostomy likely include patients with severe mucosal disease or anatomical anomalies. The technique described herein avoids mucosal anastomosis and minimizes mucosal manipulation by inserting a permanent silicone conduit from the lacrimal sac into the nasal cavity. Methods: This retrospective review of 9 surgical cases was performed with institutional review board approval. Six patients underwent 9 surgeries (3 sequentially bilateral) for dacryocystitis. Two patients had Wegener granulomatosis, 1 had pemphigoid, 1 sarcoidosis, 1 Rosai-Dorfman disease, and 1 congenital choanal atresia with chronic neonatal dacryocystitis. In each case, a modified Rains sinus stent was inserted through an external lacrimal sac incision with the draining end positioned in the nasal cavity. Two patients underwent concurrent canalicular intubation with Guibor silicone stents to prevent internal punctum obstruction by the lacrimal sac implant. Recurrence of symptoms, patient comfort, and modified Rains stent stability and patency were evaluated. Results: Mean follow up was 30 months (range 7-59 months). The modified Rains stent remained stable and patent in 7 of 9 cases, and symptoms resolved in 8 of 9 cases. In 1 patient with sarcoidosis, the modified Rains stent became repeatedly obstructed with nasal secretions and ultimately dislodged after intranasal manipulation by a physician unfamiliar with the surgery. In no other case did the patient experience recurrent infection, and in those cases, epiphora resolved entirely. In the patient with pemphigoid, one of the modified Rains stents extruded 6 months postoperatively, but his symptoms remained controlled. No adverse reaction to the implant material was seen. Conclusions: A Rains silicone frontal sinus stent can be modified for implantation into the lacrimal sac and can safely and effectively drain the lacrimal sac into the nose in patients with severe mucosal disease or anatomical anomalies. Additional study and a stent specifically designed for this application will likely improve outcomes. C1 [De Castro, Dawn K.; Fay, Aaron] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [De Castro, Dawn K.; Fay, Aaron] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Santiago, Yvette Marie B.] St Lukes Med Ctr, Int Eye Inst, Quezon City, Philippines. [Cunningham, Michael; Gray, Stacey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Cunningham, Michael; Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Gray, Stacey T.; Metson, Ralph] Boston Childrens Hosp, Dept Otolaryngol, Boston, MA USA. RP Fay, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu NR 38 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP PY 2013 VL 29 IS 5 BP 367 EP 372 DI 10.1097/IOP.0b013e31829a72d4 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 220NT UT WOS:000324592000021 PM 23880973 ER PT J AU Golberg, A AF Golberg, Alexander TI The impact of pulsed electric fields on cells and biomolecules Comment on "Lightning-triggered electroporation and electrofusion as possible contributors to natural horizontal gene transfer" by Tadej Kotnik SO PHYSICS OF LIFE REVIEWS LA English DT Editorial Material ID MEMBRANE ELECTROPORATION; DNA C1 [Golberg, Alexander] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Golberg, Alexander] Shriners Burns Inst, Boston, MA 02114 USA. RP Golberg, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. EM agolberg@partners.org OI Golberg, Alexander/0000-0001-8782-8879 NR 16 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1571-0645 EI 1873-1457 J9 PHYS LIFE REV JI Phys. Life Rev. PD SEP PY 2013 VL 10 IS 3 BP 382 EP 383 DI 10.1016/j.plrev.2013.07.025 PG 2 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 231UW UT WOS:000325444900026 PM 23948139 ER PT J AU Kelton, D Lysecki, C Aukema, H Anderson, B Kang, JX Ma, DWL AF Kelton, D. Lysecki, C. Aukema, H. Anderson, B. Kang, J. X. Ma, D. W. L. TI Endogenous synthesis of n-3 PUFA modifies fatty acid composition of kidney phospholipids and eicosanoid levels in the fat-1 mouse SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Arachidonic acid; Fat-1; Kidney; Phospholipid; Eicosanoids; Polyunsaturated fatty acids; Docosahexaenoic acid; Eicosapentaenoic acid ID DIETARY FISH-OIL; EICOSAPENTAENOIC ACID; IGA NEPHROPATHY; DOCOSAHEXAENOIC ACID; LUPUS NEPHRITIS; RENAL-DISEASE; EVOLUTIONARY ASPECTS; CONTROLLED-TRIAL; OMEGA-3; MICE AB The goal of the present study was to determine whether endogenous synthesis of n-3 polyunsaturated fatty acids (PUFA) in the fat-1 mouse is comparable to fish oil feeding with respect to kidney n-3 PUFA composition and eicosanoid levels. Wild-type and heterozygous fat-1 mice, capable of synthesizing n-3 PUFA endogenously, were given diets enriched in either n-3 or n-6 PUFA in a 2 x 2 factorial design and terminated after 12 weeks. Kidney phospholipid fatty acids were analysed by gas chromatography. Kidney eicosanoids were analysed by liquid chromatography tandem mass spectrometry. Relative to control mice fed n-6 PUFA, n-3 PUFA fed and fat-1 mice had higher levels of kidney phospholipid n-3 PUFA, and lower levels of n-6 PUFA and eicosanoids. However, mice fed n-3 PUFA mice had higher levels of n-3 PUFA and lower levels of eicosanoids as compared to fat-1 mice. In conclusion, diet feeding had a greater impact on kidney fatty acid composition and eicosanoid levels than the genetic effect of the fat-1 gene. However, the fat-1 mouse remains a close approximation that can be used as a complementary model to study the role of n-3 PUFA in the kidney. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Kelton, D.; Anderson, B.; Ma, D. W. L.] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada. [Lysecki, C.; Aukema, H.] Univ Manitoba, Dept Human Nutr Sci, Winnipeg, MB, Canada. [Kang, J. X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kang, J. X.] Harvard Univ, Sch Med, Boston, MA USA. RP Ma, DWL (reprint author), Univ Guelph, Coll Biol Sci, Dept Human Hlth & Nutr Sci, Anim Sci Nutr Bldg,Rm 342,491 Gordon St, Guelph, ON N1G 2W1, Canada. EM davidma@uoguelph.ca OI Aukema, Harold/0000-0002-6982-7239 FU Natural Sciences and Engineering Research Council [312062-2010, 217412]; Canada Foundation for Innovation and Ministry of Research and Innovation FX This study was supported by funding from the Natural Sciences and Engineering Research Council (grant #312062-2010), Canada Foundation for Innovation and Ministry of Research and Innovation to D. Ma. H. Aukema was supported by funding from the Natural Sciences and Engineering Research Council (grant #217412). We thank Lyn Hillyer for her technical expertise. NR 58 TC 3 Z9 3 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD SEP PY 2013 VL 89 IS 4 BP 169 EP 177 DI 10.1016/j.plefa.2013.08.002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 235TH UT WOS:000325743100006 PM 23994161 ER PT J AU Aschbacher, K O'Donovan, A Wolkowitz, OM Dhabhar, FS Su, YL Epel, E AF Aschbacher, Kirstin O'Donovan, Aoife Wolkowitz, Owen M. Dhabhar, Firdaus S. Su, Yali Epel, Elissa TI Good stress, bad stress and oxidative stress: Insights from anticipatory cortisol reactivity SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Oxidative stress; Biological aging; Chronic stress; Acute stress; DNA/RNA damage; Cortisol; Hypothalamic-pituitaryadrenal axis; Eustress; Resilience; Reactive oxygen species ID PSYCHOLOGICAL STRESS; IMMUNE FUNCTION; MEDIATION ANALYSIS; PERCEIVED STRESS; TELOMERE LENGTH; FREE-RADICALS; DNA-DAMAGE; RESPONSES; DISEASE; ALLOSTASIS AB Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F-2 alpha (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p < .01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants ( p <= .01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less studied model of 'eustress' - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M.; Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Aschbacher, Kirstin] Inst Integrat Hlth, Baltimore, MD USA. [O'Donovan, Aoife] San Francisco VA Med Ctr, San Francisco, CA USA. [Dhabhar, Firdaus S.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Dhabhar, Firdaus S.] Stanford Univ, Stanford Inst Immun Transplantat & Infect, Palo Alto, CA 94304 USA. [Su, Yali] SilverCreek Technol, Gilbert, AZ USA. RP Aschbacher, K (reprint author), Univ Calif San Francisco, Sch Med, Dept Psychiat, 3333 Calif St,Suite 465, San Francisco, CA 94143 USA. EM kirstin.aschbacher@ucsf.edu FU NIH/NIA [R01 AG030424-01A2]; NIH/NHLBI [K23 HL112955]; Institute for Integrative Health, Baltimore, MD; NIH/NCRR UCSF-CTSI [UL1 RR024131] FX This research was supported in part by funding from the NIH/NIA grant R01 AG030424-01A2, as well as support for the first author from the NIH/NHLBI grant K23 HL112955 and The Institute for Integrative Health, Baltimore, MD. The CTSI CCRC and the Core Immunology Lab were supported by NIH/NCRR UCSF-CTSI Grant No. UL1 RR024131. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 54 TC 47 Z9 49 U1 6 U2 61 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD SEP PY 2013 VL 38 IS 9 BP 1698 EP 1708 DI 10.1016/j.psyneuen.2013.02.004 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 228LM UT WOS:000325188300024 PM 23490070 ER PT J AU Loftis, JM AF Loftis, Jennifer M. TI Indolamine 2,3-dioxygenase regulation and neuropsychiatric symptoms SO PSYCHONEUROENDOCRINOLOGY LA English DT Letter DE Anxiety; Depression; Cytokine; Inflammation; Tryptophan ID DEPRESSION C1 [Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Res & Dev Serv, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM loftisj@ohsu.edu FU BLRD VA [I01 BX002061]; NIDA NIH HHS [P50 DA018165] NR 8 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD SEP PY 2013 VL 38 IS 9 BP 1829 EP 1830 DI 10.1016/j.psyneuen.2013.05.020 PG 2 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 228LM UT WOS:000325188300039 PM 23810316 ER PT J AU Yehuda, R Hildebrandt, T Spiegel, D AF Yehuda, Rachel Hildebrandt, Tom Spiegel, David TI Introduction to Special Issue of Psychoneuroendocrinology "Enduring effects of Traumatic Stress: Molecular and Hormonal Mechanisms" SO PSYCHONEUROENDOCRINOLOGY LA English DT Editorial Material C1 [Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY USA. [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, Bronx, NY 10468 USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY USA. [Hildebrandt, Tom] Icahn Sch Med Mt Sinai, Dept Psychiat, Eating & Weight Disorders Program, New York, NY USA. [Spiegel, David] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Div, 526 OOMH PTSD 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov OI Hildebrandt, Thomas/0000-0001-7054-9590 NR 6 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD SEP PY 2013 VL 38 IS 9 BP 1832 EP 1834 DI 10.1016/j.psyneuen.2013.06.018 PG 3 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 228LM UT WOS:000325188300041 PM 23849599 ER PT J AU Daskalakis, NP Bagot, RC Parker, KJ Vinkers, CH de Kloet, ER AF Daskalakis, Nikolaos P. Bagot, Rosemary C. Parker, Karen J. Vinkers, Christiaan H. de Kloet, E. R. TI The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Vulnerability; Resilience; Stress adaptation; Three hit; HPA axis; Developmental programming; Epigenetics Genetic predisposition; Early life environment; Later life environment ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING-FACTOR; GLUCOCORTICOID-RECEPTOR GENE; POSTTRAUMATIC-STRESS-DISORDER; MARMOSET CALLITHRIX-JACCHUS; INFANT SQUIRREL-MONKEYS; EARLY SOCIAL ENRICHMENT; MATERNAL-CARE; DIFFERENTIAL SUSCEPTIBILITY; ADRENOCORTICAL-RESPONSE AB Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Daskalakis, Nikolaos P.] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY USA. [Daskalakis, Nikolaos P.] Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY USA. [Daskalakis, Nikolaos P.] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, PTSD Clin Res Program, Bronx, NY USA. [Daskalakis, Nikolaos P.] James J Peters Vet Affairs Med Ctr, Lab Clin Neuroendocrinol & Neurochem, Bronx, NY USA. [Daskalakis, Nikolaos P.; de Kloet, E. R.] Leiden Univ, Leiden Acad, Ctr Drug Res, Div Med Pharmacol, Leiden, Netherlands. [Daskalakis, Nikolaos P.; de Kloet, E. R.] Leiden Univ, Leiden Univ Med Ctr, Leiden, Netherlands. [Bagot, Rosemary C.] Douglas Mental Hlth Univ Inst, Neurosci Div, Montreal, PQ, Canada. [Bagot, Rosemary C.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Fishberg Dept Neurosci, Lab Mol Psychiat, New York, NY USA. [Parker, Karen J.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Vinkers, Christiaan H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Vinkers, Christiaan H.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacol, Utrecht, Netherlands. [Vinkers, Christiaan H.] Univ Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. RP Daskalakis, NP (reprint author), Mt Sinai Sch Med, Lab Mol Neuropsychiat, 1 Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM Nikolaos.daskalakis@mssm.edu RI Daskalakis, Nikolaos/B-7930-2014; Parker, Karen/G-1347-2012 OI Parker, Karen/0000-0002-6836-6338; Daskalakis, Nikolaos/0000-0003-1660-9112; FU Dutch Top-Institute Pharma [T5-209]; Royal Netherlands Academy for Sciences; [NIH-R01HD67175] FX We would like to thank the organizers of 42nd ISPNE Conference for choosing our proposal for a Symposium. We would like to thank Dr. Esther Nederhof for participating as a speaker in the Symposium. ND and EdK were supported by the Dutch Top-Institute Pharma T5-209, and KP by the NIH-R01HD67175. EdK was also supported by the Royal Netherlands Academy for Sciences. NR 200 TC 75 Z9 75 U1 10 U2 72 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD SEP PY 2013 VL 38 IS 9 BP 1858 EP 1873 DI 10.1016/j.psyneuen.2013.06.008 PG 16 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 228LM UT WOS:000325188300045 PM 23838101 ER PT J AU van Ast, VA Cornelisse, S Marin, MF Ackermann, S Garfinkel, SN Abercrombie, HC AF van Ast, Vanessa A. Cornelisse, Sandra Marin, Marie-France Ackermann, Sandra Garfinkel, Sarah N. Abercrombie, Heather C. TI Modulatory mechanisms of cortisol effects on emotional learning and memory: Novel perspectives SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Cortisol; Stress; Memory; Encoding; Consolidation; Modulators; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; LONG-TERM POTENTIATION; POLYMORPHISMS; AMYGDALA; IMPAIRS; CONTEXT; BRAIN; GLUCOCORTICOIDS; RECONSOLIDATION; ENVIRONMENTS AB It has long been known that cortisol affects learning and memory processes. Despite a wealth of research dedicated to cortisol effects on learning and memory, the strength or even directionality of the effects often vary. A number of the factors that alter cortisol's effects on learning and memory are well-known. For instance, effects of cortisol can be modulated by emotional arousal and the memory phase under study. Despite great advances in understanding factors that explain variability in cortisol's effects, additional modulators of cortisol effects on memory exist that are less widely acknowledged in current basic experimental research. The goal of the current review is to disseminate knowledge regarding less well-known modulators of cortisol effects on learning and memory. Since several models for the etiology of anxiety, such as post-traumatic stress disorder (PTSD), incorporate stress and the concomitant release of cortisol as important vulnerability factors, enhanced understanding of mechanisms by which cortisol exerts beneficial as opposed to detrimental effects on memory is very important. Further elucidation of the factors that modulate (or alter) cortisol's effects on memory will allow reconciliation of seemingly inconsistent findings in the basic and clinical literatures. The present review is based on a symposium as part of the 42nd International Society of Psychoneuroendocrinology Conference, New York, USA, that highlighted some of those modulators and their underlying mechanisms. (C) 2013 Elsevier Ltd. All rights reserved. C1 [van Ast, Vanessa A.] Univ Amsterdam, Dept Clin Psychol, NL-1018 WB Amsterdam, Netherlands. [Cornelisse, Sandra] Univ Med Ctr Utrecht, Dept Neurosci & Pharmacol, Rudolf Magnus Inst Neurosci, NL-3584 CG Utrecht, Netherlands. [Marin, Marie-France] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Marin, Marie-France] Univ Montreal, Ctr Studies Human Stress, Mental Hlth Univ Inst Montreal, Montreal, PQ, Canada. [Ackermann, Sandra] Univ Basel, Dept Psychol, Div Mol Neurosci, Basel, Switzerland. [Garfinkel, Sarah N.] Sussex Med Sch, Sackler Ctr Consciousness Sci, Brighton, E Sussex, England. [Abercrombie, Heather C.] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Cornelisse, S (reprint author), Univ Med Ctr Utrecht, Dept Neurosci & Pharmacol, Rudolf Magnus Inst Neurosci, Univ Weg 100, NL-3584 CG Utrecht, Netherlands. EM s.cornelisse-5@umcutrecht.nl FU TopTalent grant [021.002.103]; National Institutes of Health [1K08MH07415, R01 MH094478]; NARSAD Young Investigator Award FX We would like to thank the organizers of the 42nd International Society of Psychoneuroendocrinology Conference, New York, USA arranging the conference as well as this special edition of Psychoneuroendocrinology. Further, we would like to thank the attendees of our symposium for interesting discussion. This work was supported by a TopTalent grant (Vanessa A. van Ast, #021.002.103). The work was also supported in part by National Institutes of Health grants (1K08MH07415 and R01 MH094478) and a NARSAD Young Investigator Award to Heather Abercrombie. NR 57 TC 5 Z9 6 U1 3 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD SEP PY 2013 VL 38 IS 9 BP 1874 EP 1882 DI 10.1016/j.psyneuen.2013.06.012 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 228LM UT WOS:000325188300046 PM 23845515 ER PT J AU Daskalakis, NP Yehuda, R Diamond, DM AF Daskalakis, Nikolaos P. Yehuda, Rachel Diamond, David M. TI Animal models in translational studies of PTSD SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Post-traumatic stress disorder; PTSD; Animal model; Translational; Bionnarkers; Therapeutics; Individual differences ID POSTTRAUMATIC-STRESS-DISORDER; HIPPOCAMPUS-DEPENDENT MEMORY; NATIONAL COMORBIDITY SURVEY; BDNF VAL66MET POLYMORPHISM; MENSTRUAL-CYCLE MODULATION; MEDIAL PREFRONTAL CORTEX; HIGH-DOSE CORTICOSTERONE; LONG-TERM POTENTIATION; HEALTHY-YOUNG MEN; DSM-IV DISORDERS AB Understanding the neurobiological mechanisms of post-traumatic stress disorder (PTSD) is of vital importance for developing biomarkers and more effective pharmacotherapy for this disorder. The design of bidirectional translational studies addressing all facets of PTSD is needed. Animal models of PTSD are needed not only to capture the complexity of PTSD behavioral characteristics, but also to address experimentally the influence of variety of factors which might determine an individual's vulnerability or resilience to trauma, e.g., genetic predisposition, early-life experience and social support. The current review covers recent translational approaches to bridge the gap between human and animal PTSD research and to create a framework for discovery of biomarkers and novel therapeutics. Published by Elsevier Ltd. C1 [Daskalakis, Nikolaos P.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY USA. [Daskalakis, Nikolaos P.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY USA. [Daskalakis, Nikolaos P.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Mental Hlth Care Ctr, PTSD Clin Res Program, Bronx, NY USA. [Daskalakis, Nikolaos P.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Lab Clin Neuroendocrinol & Neurochem, Bronx, NY USA. [Diamond, David M.] Vet Affairs Hosp, Res & Dev Serv, Tampa, FL USA. [Diamond, David M.] Univ S Florida, Dept Psychol, Ctr Preclin & Clin Res PTSD, Tampa, FL 33620 USA. [Diamond, David M.] Univ S Florida, Dept Mol Pharmacol & Physiol, Ctr Preclin & Clin Res PTSD, Tampa, FL 33620 USA. RP Diamond, DM (reprint author), Univ S Florida, Dept Psychol, 4202 E Fowler Ave,PCD 4118G, Tampa, FL 33620 USA. EM ddiamond@usf.edu RI Daskalakis, Nikolaos/B-7930-2014 OI Daskalakis, Nikolaos/0000-0003-1660-9112 FU Department of Defense grant; Veterans Affairs Department FX We would like to thank the organizers of 42nd ISPNE Conference for choosing our proposal for a Symposium. We would like to thank Dr. Israel Liberzon and Dr. Joseph Rayman for participating as speakers in the Symposium. DMD was supported by Career Scientist and Merit Review Awards from the Veterans Affairs Department during the production of this review. NPD and RY were supported by a Department of Defense grant. The opinions expressed in this review are those of the authors and not of the Department of Veterans Affairs, Department of Defense or the US government. NR 276 TC 38 Z9 39 U1 7 U2 42 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD SEP PY 2013 VL 38 IS 9 BP 1895 EP 1911 DI 10.1016/j.psyneuen.2013.06.006 PG 17 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 228LM UT WOS:000325188300048 PM 23845512 ER PT J AU Yehuda, R Neylan, TC Flory, JD McFarlane, AC AF Yehuda, Rachel Neylan, Thomas C. Flory, Janine D. McFarlane, Alexander C. TI The use of biomarkers in the military: From theory to practice SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Biomarker; PTSD; Trauma; Military; Risk; Resilience; Neurobiology; Combat exposure ID POSTTRAUMATIC-STRESS-DISORDER; RISK-FACTORS; TRAUMA; PTSD; RESILIENCE; DEPRESSION; DEPLOYMENT; VETERANS; EXPOSURE; IDENTIFICATION AB This paper provides a summary of relevant issues covered in the conference, "The Use of Biomarkers in the Military: Theory to Practice" held at the New York Academy of Science on September 14, 2012. The conference covered the state of the science in identification of PTSD biomarkers, including, the definition of different classes of biomarkers pertaining to PTSD. The aim of the satellite conference was to bring together researchers who have been supported by the Department of Defense, Veterans Administration, National Institutes of Health, and other agencies around the world, who are interested in the identification of biomarkers for PTSD risk, diagnosis, symptom severity and treatment response, for a discussion of salient issues regarding biomarker development for PTSD, as well as special considerations for the use of biomarkers in the military. (C) 2013 Published by Elsevier Ltd. C1 [Yehuda, Rachel; Flory, Janine D.] James J Peters VAMC, Dept Psychiat, Bronx, NY 10468 USA. [Yehuda, Rachel; Flory, Janine D.] Mt Sinai Sch Med, Dept Psychiat & Neurosci, New York, NY USA. [Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Neylan, Thomas C.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [McFarlane, Alexander C.] Univ Adelaide, Dept Psychiat, Adelaide, SA, Australia. RP Yehuda, R (reprint author), James J Peters VAMC, 526 OOMH,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov FU DOD [W81XWH-10-2-0072, W81XWH-09-2-0044] FX This work was supported by the following funding: DOD W81XWH-10-2-0072 (RY) and DOD W81XWH-09-2-0044 (RY) NR 43 TC 13 Z9 13 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD SEP PY 2013 VL 38 IS 9 BP 1912 EP 1922 DI 10.1016/j.psyneuen.2013.06.009 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 228LM UT WOS:000325188300049 PM 23927936 ER PT J AU Fehling, M Nelson, BD Ahn, R Eckardt, M Tiernan, M Purcell, G El-Bashir, A Burke, TF AF Fehling, M. Nelson, B. D. Ahn, R. Eckardt, M. Tiernan, M. Purcell, G. El-Bashir, A. Burke, T. F. TI Development of a community-based maternal, newborn and child emergency training package in South Sudan SO PUBLIC HEALTH LA English DT Article DE Training; Curriculum; Maternal health; Newborn health; Child health; Traditional birth attendant ID TRADITIONAL BIRTH ATTENDANTS; MILLENNIUM DEVELOPMENT GOALS; LOW-RESOURCE SETTINGS; DYING EVERY YEAR; POSTPARTUM HEMORRHAGE; COST-EFFECTIVENESS; NEONATAL DEATHS; MORTALITY; CARE; PAKISTAN AB Objective: To develop an evidence-based maternal, newborn and child emergency training package for community-based frontline health workers (FHWs) in post-conflict South Sudan. Methods: In partnership with the new Republic of South Sudan, a multimodal needs assessment was conducted through purposive sampling, involving key informant interviews, focus group discussions, provider knowledge assessments and facility surveys. Data were analyzed using traditional qualitative techniques and compared with existing training programmes and curricula. These findings informed the development and implementation of the novel training approach. Results: The needs assessment involved 33 FHWs, eight diverse health facilities in Eastern Equatoria, and stakeholders within 18 governmental and non-governmental organizations. Significant consensus emerged regarding the need for greater capacity among previously untrained FHWs. A maternal, newborn and child health training package was developed that included: (1) a participatory training course taught through a 'training of trainers' approach; (2) nine different pictorial action-based checklists covering basic management and referral of maternal, newborn and child emergencies; and (3) essential setting-appropriate equipment. Conclusion: A novel maternal, newborn and child survival package was developed for previously untrained and illiterate FHWs in South Sudan. It is hoped that this approach will build community-based capacity in resource-limited settings while greater capacity is being developed for facility-based deliveries by skilled birth attendants. (C) 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved. C1 [Fehling, M.; Nelson, B. D.; Ahn, R.; Eckardt, M.; Tiernan, M.; Purcell, G.; El-Bashir, A.; Burke, T. F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Fehling, M.; Tiernan, M.] Maternal Newborn & Child Survival Initiat, Juba, South Sudan, Sudan. [Nelson, B. D.; Ahn, R.; El-Bashir, A.; Burke, T. F.] Harvard Univ, Sch Med, Boston, MA USA. [Nelson, B. D.; Burke, T. F.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. [Eckardt, M.] Boston Med Ctr, Boston, MA USA. [Burke, T. F.] Boston Childrens Hosp, Boston, MA USA. RP Fehling, M (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, 0 Emerson Pl, Boston, MA 02114 USA. EM maya.fehling@gmail.com OI Nelson, Brett/0000-0002-5049-1798 FU Republic of South Sudan Ministry of Health; Multi-Donor Trust Fund for South Sudan FX This project was funded by the Republic of South Sudan Ministry of Health and the Multi-Donor Trust Fund for South Sudan. NR 69 TC 1 Z9 1 U1 2 U2 11 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0033-3506 EI 1476-5616 J9 PUBLIC HEALTH JI Public Health PD SEP PY 2013 VL 127 IS 9 BP 797 EP 805 DI 10.1016/j.puhe.2013.01.010 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 233YI UT WOS:000325605200002 PM 23958386 ER PT J AU Hula, WD Cherney, LR Worrall, LE AF Hula, William D. Cherney, Leora R. Worrall, Linda E. TI Setting a Research Agenda to Inform Intensive Comprehensive Aphasia Programs SO TOPICS IN STROKE REHABILITATION LA English DT Article DE aphasia; cost-benefit analysis; rehabilitation; treatment efficacy; treatment effectiveness; treatment outcome ID CLINICAL-OUTCOME RESEARCH; INDUCED LANGUAGE THERAPY; RANDOMIZED-TRIALS; CLUSTER RANDOMIZATION; CONSORT STATEMENT; BROCAS APHASIA; STROKE; RECOVERY; EFFICACY; HEALTH AB Research into intensive comprehensive aphasia programs (ICAPs) has yet to show that this service delivery model is efficacious, effective, has cost utility, or can be broadly implemented. This article describes a phased research approach to the study of ICAPs and sets out a research agenda that considers not only the specific issues surrounding ICAPs, but also the phase of the research. Current ICAP research is in the early phases, with dosing and outcome measurement as prime considerations as well as refinement of the best treatment protocol. Later phases of ICAP research are outlined, and the need for larger scale collaborative funded research is recognized. The need for more rapid translation into practice is also acknowledged, and the use of hybrid models of phased research is encouraged within the ICAP research agenda. C1 [Hula, William D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hula, William D.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. [Cherney, Leora R.] Rehabil Inst Chicago, Ctr Aphasia Res & Treatment, Chicago, IL USA. [Cherney, Leora R.] Northwestern Univ, Chicago, IL 60611 USA. [Worrall, Linda E.] Univ Queensland, Sch Hlth & Rehabil Sci, Brisbane, Qld, Australia. RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RI Worrall, Linda/D-2579-2010 OI Worrall, Linda/0000-0002-3283-7038 FU Veterans Affairs Rehabilitation Research and Development Career Development Award [C6210M]; NHMRC [569935] FX We acknowledge the Veterans Affairs Rehabilitation Research and Development Career Development Award C6210M and NHMRC grant 569935 to the Centre for Clinical Research Excellence in Aphasia Rehabilitation. NR 69 TC 4 Z9 4 U1 2 U2 13 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119-3627 USA SN 1074-9357 J9 TOP STROKE REHABIL JI Top. Stroke Rehabil. PD SEP-OCT PY 2013 VL 20 IS 5 BP 409 EP 420 DI 10.1310/tsr2005-409 PG 12 WC Rehabilitation SC Rehabilitation GA 231WE UT WOS:000325448300005 PM 24091283 ER PT J AU Votruba, KL Rapport, LJ Whitman, RD Johnson, A Langenecker, S AF Votruba, Kristen L. Rapport, Lisa J. Whitman, R. Douglas Johnson, Alex Langenecker, Scott TI Personality Differences among Patients with Chronic Aphasia Predict Improvement in Speech-Language Therapy SO TOPICS IN STROKE REHABILITATION LA English DT Article DE affectivity; depression; executive functioning; speech-language therapy ID QUALITY-OF-LIFE; STROKE IMPACT SCALE; POSTSTROKE DEPRESSION; LESION LOCATION; POSITIVE AFFECT; NEGATIVE AFFECT; RECOVERY; STRESS; HEALTH; IMPAIRMENT AB Background: Negative affectivity and neurocognitive deficits including executive dysfunction have been shown to be detrimental to rehabilitation therapies. However, research on the relationship between neuropsychological deficits and improvement in speech-language therapy (SLT) for aphasia is sparse. Objective: To examine the relationships among neurocognitive and psychological functioning and improvement in SLT following aphasia due to stroke. Methods: Fifty patients who were >= 9 months post stroke and enrolled in outpatient SLT to treat aphasia participated. Using standard language assessment measures, the authors evaluated language functioning at initiation of the study and after participants completed various SLT protocols. Executive functioning, visuospatial skills, attention, and memory also were assessed to provide indices of convergent and discriminant validity. Participants' mood and affectivity were evaluated by self-report, and their functional abilities and recovery of function since stroke were assessed via caregiver report. Results: A multiple regression model testing the combined powers of neurocognitive and psychological variables was significant (P=.004, R-2 = 0.33), with psychological and neurocognitive functioning accounting for 15% of the variance in relative language change beyond that accounted for by stroke severity and gross cognitive functioning. Negative affectivity expressed on the Positive and Negative Affectivity Scale made unique contributions to the model. Conclusions: Improvement in SLT is substantially related to neurocognitive and psychological functioning, particularly affectivity. Assessment of these characteristics may assist in identifying patients who are likely to improve and in tailoring treatment programs to yield optimal outcomes. C1 [Votruba, Kristen L.; Rapport, Lisa J.; Whitman, R. Douglas] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. [Johnson, Alex] Wayne State Univ, Dept Audiol, Detroit, MI USA. [Johnson, Alex] Massachusetts Gen Hosp, Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA 02114 USA. [Langenecker, Scott] Univ Michigan, Med Ctr, Dept Psychiat, Neuropsychol Sect, Ann Arbor, MI 48109 USA. RP Votruba, KL (reprint author), Univ Michigan, Med Ctr, Dept Psychiat, Neuropsychol Sect, Ann Arbor, MI 48109 USA. FU Wayne State University FX This study was supported by a grant from Wayne State University (dissertation research grant). Results of this study were presented at the annual meeting of the American Psychological Association; August 17, 2008; Boston, Massachusetts. NR 60 TC 8 Z9 8 U1 0 U2 19 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119-3627 USA SN 1074-9357 J9 TOP STROKE REHABIL JI Top. Stroke Rehabil. PD SEP-OCT PY 2013 VL 20 IS 5 BP 421 EP 431 DI 10.1310/tsr2005-421 PG 11 WC Rehabilitation SC Rehabilitation GA 231WE UT WOS:000325448300006 PM 24091284 ER PT J AU Juan, J Hind, J Jones, C McCulloch, T Gangnon, R Robbins, J AF Juan, Junerose Hind, Jacqueline Jones, Corinne McCulloch, Timothy Gangnon, Ron Robbins, JoAnne TI Case Study: Application of Isometric Progressive Resistance Oropharyngeal Therapy Using the Madison Oral Strengthening Therapeutic Device SO TOPICS IN STROKE REHABILITATION LA English DT Article DE deglutition; dysphagia; rehabilitation; strengthening; stroke ID NECK-CANCER PATIENTS; PENETRATION-ASPIRATION SCALE; QOL OUTCOMES TOOL; SWAL-QOL; DYSPHAGIA; STROKE; ADULTS; PNEUMONIA; EXERCISE; MUSCLE AB Purpose: Isometric progressive resistance oropharyngeal (I-PRO) therapy improves swallowing function; however, current devices utilize a single sensor that provides limited information or are prohibitively expensive. This single-subject study presents results of I-PRO therapy, detraining, and maintenance using the 5-sensor Madison Oral Strengthening Therapeutic (MOST) device combined with upper esophageal sphincter (UES) dilatation. Methods: A 56-year-old female nurse who was 27 months post stroke and subsequent to traditional behavioral interventions and UES dilatations presented limited to gastrostomy tube intake only and expectorating all saliva. She completed 8 weeks of I-PRO therapy, 5 weeks of detraining, and 9 weeks of I-PRO maintenance (reduced frequency) followed by a third UES dilatation post intervention. Data included diet inventory, lingual pressures (MOST), lingual volume (magnetic resonance imaging), postswallow residue (videofluoroscopy), UES and pharyngeal pressures (high-resolution manometry), and quality of life (QOL). Results: Findings after 8 weeks of I-PRO therapy were progression to general oral diet, 15 lb weight gain, increased isometric pressures (Delta > 16 kPa) with transference to swallowing pressures, increased lingual volume (8.3%), reduced pharyngeal wall residue (P = .03), increased pharyngeal pressures (Delta > 43 mm Hg) and increased UES opening (nadir) pressures(Delta > 9 mm Hg) with improved temporopressure coordination across the pharynx, and improved QOL. After detraining, decreased isometric pressures and reduced UES opening were noted. After I-PRO maintenance, isometric anterior lingual pressures returned to levels noted after the 8 weeks of intervention. Conclusion: I-PRO therapy, facilitated by the MOST device combined with instrumental UES dilatation, improved swallow safety, increased oropharyngeal intake, and facilitated UES opening while enriching QOL. C1 [Juan, Junerose; Hind, Jacqueline; Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. [Juan, Junerose; Hind, Jacqueline; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ Clin Ctr, Madison, WI USA. [Jones, Corinne; McCulloch, Timothy] Univ Wisconsin, Dept Surg, Madison, WI USA. [Gangnon, Ron] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. RP Juan, J (reprint author), Univ Wisconsin, Dept Med, Madison, WI USA. FU VA Merit Grant [C4796R] FX This article is the result of work supported by VA Merit Grant C4796R and resources at the Geriatric Research, Education, and Clinical Center (GRECC) in the William S. Middleton Memorial Veterans Hospital. This is GRECC manuscript #09. The senior author, Dr. Robbins, serves in a leadership position for Swallow Solutions, LLC, and is an equity holder. NR 31 TC 1 Z9 1 U1 2 U2 11 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119-3627 USA SN 1074-9357 J9 TOP STROKE REHABIL JI Top. Stroke Rehabil. PD SEP-OCT PY 2013 VL 20 IS 5 BP 450 EP 470 DI 10.1310/tsr2005-450 PG 21 WC Rehabilitation SC Rehabilitation GA 231WE UT WOS:000325448300009 PM 24091287 ER PT J AU Tomlinson, L Boone, LI Ramaiah, L Penraat, KA von Beust, BR Ameri, M Poitout-Belissent, FM Weingand, K Workman, HC Aulbach, AD Meyer, DJ Brown, DE MacNeill, AL Bolliger, AP Bounous, DI AF Tomlinson, Lindsay Boone, Laura I. Ramaiah, Lila Penraat, Kelley A. von Beust, Barbara R. Ameri, Mehrdad Poitout-Belissent, Florence M. Weingand, Kurt Workman, Heather C. Aulbach, Adam D. Meyer, Dennis J. Brown, Diane E. MacNeill, Amy L. Bolliger, Anne Provencher Bounous, Denise I. TI Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries SO VETERINARY CLINICAL PATHOLOGY LA English DT Article DE Biomarkers; laboratory standards; preclinical development; preclinical safety; translational medicine ID BIOANALYTICAL METHOD VALIDATION; ASSURANCE GUIDELINES CONTROL; LIGAND-BINDING ASSAYS; TEST-STRIP; PRECLINICAL TOXICOLOGY; BRONCHOALVEOLAR LAVAGE; LACTATE-DEHYDROGENASE; REFERENCE INTERVALS; DRUG DEVELOPMENT; REFERENCE VALUES AB The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. C1 [Tomlinson, Lindsay] Pfizer Inc, Drug Safety & Res Dev, Cambridge, MA USA. [Boone, Laura I.; Workman, Heather C.] Covance Labs Inc, Greenfield, IN USA. [Ramaiah, Lila] Huntingdon Life Sci, E Millstone, NJ USA. [Penraat, Kelley A.] Alpha Omega Vet Consultant Serv, Lafayette, NJ USA. [von Beust, Barbara R.] Lab Zugersee, Hunenberg, Switzerland. [Ameri, Mehrdad] Amgen Inc, Dept Pathol, Thousand Oaks, CA 91320 USA. [Poitout-Belissent, Florence M.; Meyer, Dennis J.; Bolliger, Anne Provencher] Charles River Labs, Clin Pathol, Reno, NV USA. [Weingand, Kurt] SciComPro LLC, Phoenix, AZ USA. [Aulbach, Adam D.] MPI Res, Mattawan, MI USA. [Brown, Diane E.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [MacNeill, Amy L.] Univ Illinois, Dept Pathobiol, Urbana, IL 61801 USA. [Bounous, Denise I.] Bristol Myers Squibb Co, Discovery Toxicol, Lawrenceville, NJ USA. RP Tomlinson, L (reprint author), Pfizer Inc, Drug Safety & Res Dev, Cambridge, MA USA. EM lindsay.tomlinson@pfizer.com RI MacNeill, Amy/D-6066-2017 OI MacNeill, Amy/0000-0002-1690-3787 NR 97 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0275-6382 EI 1939-165X J9 VET CLIN PATH JI Vet. Clin. Pathol. PD SEP PY 2013 VL 42 IS 3 BP 252 EP 269 DI 10.1111/vcp.12059 PG 18 WC Veterinary Sciences SC Veterinary Sciences GA 217YU UT WOS:000324400200003 PM 23889060 ER PT J AU Benassi, B Marani, M Loda, M Blandino, G AF Benassi, B. Marani, M. Loda, M. Blandino, G. TI USP2a alters chemotherapeutic response by modulating redox SO CELL DEATH & DISEASE LA English DT Article DE USP2a; miR-34b/c; c-Myc; GSH; chemotherapy; prostate cancer ID HUMAN PROSTATE-CANCER; ATTENUATES PACLITAXEL-RESISTANCE; DEUBIQUITINATING ENZYME USP2A; SQUAMOUS-CELL CARCINOMA; FATTY-ACID SYNTHASE; C-MYC; OXIDATIVE STRESS; MICRORNA EXPRESSION; PC3 CELLS; PROTEASOME INHIBITORS AB Cancer cells are characterized by altered ubiquitination of many proteins. The ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme overexpressed in prostate adenocarcinomas, where it exhibits oncogenic behavior in a variety of ways including targeting c-Myc via the miR-34b/c cluster. Here we demonstrate that USP2a induces drug resistance in both immortalized and transformed prostate cells. Specifically, it confers resistance to typically pro-oxidant agents, such as cisplatin (CDDP) and doxorubicin (Doxo), and to taxanes. USP2a overexpression protects from drug-induced oxidative stress by reducing reactive oxygen species (ROS) production and stabilizing the mitochondrial membrane potential (Delta Psi), thus impairing downstream p38 activation and triggering of apoptosis. The molecular mediator of the USP2a protective function is the glutathione (GSH). Through miR-34b/c-driven c-Myc regulation, USP2a increases intracellular GSH content, thus interfering with the oxidative cascade triggered by chemotherapeutic agents. In light of these findings, targeting Myc and/or miR-34b/c might revert chemo-resistance. C1 [Benassi, B.] ENEA Casaccia, Unit Radiat Biol & Human Hlth, I-00123 Rome, Italy. [Marani, M.] Italian Natl Canc Inst Regina Elena, Dept Mol Med, Rome, Italy. [Loda, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, M.] Kings Coll London, Div Canc Studies, London, England. [Blandino, G.] Italian Natl Canc Inst Regina Elena, Translat Oncogen Unit, Rome, Italy. RP Benassi, B (reprint author), ENEA Casaccia, Unit Radiat Biol & Human Hlth, Via Anguillarese 301, I-00123 Rome, Italy. EM barbara.benassi@enea.it OI Marani, Marina/0000-0003-1585-3586 NR 60 TC 8 Z9 8 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD SEP PY 2013 VL 4 AR e812 DI 10.1038/cddis.2013.289 PG 10 WC Cell Biology SC Cell Biology GA 230VC UT WOS:000325370300029 PM 24071644 ER PT J AU Mayes, DA Rizvi, TA Titus-Mitchell, H Oberst, R Ciraolo, GM Vorhees, CV Robinson, AP Miller, SD Cancelas, JA Stemmer-Rachamimov, AO Ratner, N AF Mayes, Debra A. Rizvi, Tilat A. Titus-Mitchell, Haley Oberst, Rachel Ciraolo, Georgianne M. Vorhees, Charles V. Robinson, Andrew P. Miller, Stephen D. Cancelas, Jose A. Stemmer-Rachamimov, Anat O. Ratner, Nancy TI Nf1 Loss and Ras Hyperactivation in Oligodendrocytes Induce NOS-Driven Defects in Myelin and Vasculature SO CELL REPORTS LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; IN-VIVO; BRAIN; CELLS; DIFFERENTIATION; PROGENITORS; EXPRESSION; MOUSE AB Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor NG-nitro-L-arginine methyl ester or the antioxidant N-acetyl cysteine corrected cellular phenotypes. CNP-HRasG12V mice also displayed locomotor hyperactivity, which could be rescued by antioxidant treatment. We conclude that Nf1/Ras regulates oligodendrocyte NOS and that dysregulated NO signaling in oligodendrocytes can alter the surrounding vasculature. The data suggest that antioxidants may improve some behavioral deficits in Rasopathy patients. C1 [Mayes, Debra A.; Rizvi, Tilat A.; Titus-Mitchell, Haley; Oberst, Rachel; Cancelas, Jose A.; Ratner, Nancy] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Ciraolo, Georgianne M.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA. [Vorhees, Charles V.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH 45229 USA. [Robinson, Andrew P.; Miller, Stephen D.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ratner, N (reprint author), Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. EM nancy.ratner@cchmc.org OI Titus, Haley/0000-0002-2327-9791; Robinson, Andrew/0000-0002-1867-5634 FU DAMD Program on Neurofibromatosis [W81XWH-06-1-0114, W81XWH-10-1-0116]; Children's Tumor Foundation; NIH NRSA [T32CA117846]; National Multiple Sclerosis Society [FG1762A1/1] FX We thank Brian Popko (University of Chicago) for providing the inducible Plp-Cre-ERT mice, and Luis Parada (UTSW) for the Nf1fl/fl mice. We also thank Nathan Kalasinski for carrying out some of the mouse genotyping for this project, and Peter Pytel (University of Chicago) for performing the autopsy on the NF1 patient studied. This work was supported by grants from the DAMD Program on Neurofibromatosis (W81XWH-06-1-0114 and W81XWH-10-1-0116 to N.R.) and a Drug Discovery Initiative Award from the Children's Tumor Foundation. D. A. M. was partially supported by grants from the NIH NRSA (T32CA117846) and the National Multiple Sclerosis Society (FG1762A1/1). D. A. M. performed all animal work and experiments, analyzed and interpreted data, identified the phenotypes and developed the mechanism, created the figures, and wrote and edited the paper. T. A. R. performed the Ras activation assay, characterized cells affected by the HRas mutation in the CNP-HRas animals, and performed the NOS stain on sections. G. C. prepared sections for electron microscopy. R.O. helped in animal behavior experiments and C. V. analyzed animal behavior. H. T. M. and J.C. performed the flow cytometry and interpreted the results. A. P. R. and S. D. M. provided the mature oligodendrocyte dissociation protocol for flow cytometry. A.O.S. analyzed stained brain and optic-nerve section histology and pathology. N.R. conceptualized the original experimental plan, aided in data analysis and interpretation, and edited the paper and figures. NR 53 TC 11 Z9 11 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD SEP PY 2013 VL 4 IS 6 BP 1197 EP 1212 DI 10.1016/j.celrep.2013.08.011 PG 16 WC Cell Biology SC Cell Biology GA 230KB UT WOS:000325336500014 PM 24035394 ER PT J AU Reschke, M Clohessy, JG Seitzer, N Goldstein, DP Breitkopf, SB Schmolze, DB Ala, U Asara, JM Beck, AH Pandolfi, PP AF Reschke, Markus Clohessy, John G. Seitzer, Nina Goldstein, Daniel P. Breitkopf, Susanne B. Schmolze, Daniel B. Ala, Ugo Asara, John M. Beck, Andrew H. Pandolfi, Pier Paolo TI Characterization and Analysis of the Composition and Dynamics of the Mammalian Riboproteome SO CELL REPORTS LA English DT Article ID AMINO-ACIDS; CANCER; NUCLEOPHOSMIN; MECHANISM; RIBOSOMES; PROTEOME; LEUKEMIA; BIOLOGY; PIK3CA; MTORC1 AB Increasing evidence points to an important role for the ribosome in the regulation of biological processes and as a target for deregulation in disease. Here, we describe a SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry approach to probing mammalian riboproteomes. Using a panel of cell lines, as well as genetic and pharmacological perturbations, we obtained a comparative characterization of the cellular riboproteome. This analysis identified a set of riboproteome components, consisting of a diverse array of proteins with a strong enrichment for RNA-binding proteins. Importantly, this global analysis uncovers a high incidence of genetic alterations to riboproteome components in cancer, with a distinct bias toward genetic amplification. We further validated association with polyribosomes for several riboproteome components and demonstrate that enrichment at the riboproteome can depend on cell type, genetics, or cellular stimulus. Our results have important implications for the understanding of how ribosomes function and provide a platform for uncovering regulators of translation. C1 [Reschke, Markus; Clohessy, John G.; Seitzer, Nina; Goldstein, Daniel P.; Ala, Ugo; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Genet Program,Dept Med & Pathol, Boston, MA 02215 USA. [Breitkopf, Susanne B.; Asara, John M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct,Dept Med, Boston, MA 02215 USA. [Schmolze, Daniel B.; Beck, Andrew H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Schmolze, Daniel B.; Beck, Andrew H.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Ala, Ugo] Univ Turin, Mol Biotechnol Ctr, I-10124 Turin, Italy. [Ala, Ugo] Univ Turin, Dept Genet Biol & Biochem, I-10124 Turin, Italy. RP Pandolfi, PP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Genet Program,Dept Med & Pathol, Boston, MA 02215 USA. EM ppandolf@bidmc.harvard.edu RI Ala, Ugo/K-2029-2016 OI Ala, Ugo/0000-0001-5408-6397 FU NIH [RC1 DK087679, 5P01CA120964-04]; German Academy of Sciences Leopoldina (Leopoldina Research Fellowship) [LPDS 2009-27]; AIRC [IG-9408]; NIH DF/HCC Cancer Center Support Grant [5P30CA006516-46] FX We would like to thank all Pandolfi laboratory members for critical discussions. We would like to thank Min Yuan of the BIDMC Mass Spectrometry Core for help with sample preparation. This research was supported by NIH grant RC1 DK087679 to P. P. P. M. R. received support from the German Academy of Sciences Leopoldina (Leopoldina Research Fellowship grant number: LPDS 2009-27). U.A. received support from AIRC under grant IG-9408. J.M.A. received support from grants NIH 5P01CA120964-04 and NIH DF/HCC Cancer Center Support Grant 5P30CA006516-46. NR 26 TC 15 Z9 15 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD SEP PY 2013 VL 4 IS 6 BP 1276 EP 1287 DI 10.1016/j.celrep.2013.08.014 PG 12 WC Cell Biology SC Cell Biology GA 230KB UT WOS:000325336500020 PM 24055062 ER PT J AU Papakostas, TD Lee, NG Lefebvre, DR Barshak, MB Freitag, SK AF Papakostas, Thanos D. Lee, N. Grace Lefebvre, Daniel R. Barshak, Miriam B. Freitag, Suzanne K. TI Endogenous panophthalmitis with orbital cellulitis secondary to Escherichia coli SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID ENDOPHTHALMITIS C1 [Papakostas, Thanos D.; Lee, N. Grace; Lefebvre, Daniel R.; Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Barshak, Miriam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Infect Dis, Boston, MA USA. RP Papakostas, TD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1442-6404 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD SEP PY 2013 VL 41 IS 7 BP 716 EP 718 DI 10.1111/ceo.12094 PG 3 WC Ophthalmology SC Ophthalmology GA 227WP UT WOS:000325146700016 PM 23432793 ER PT J AU Marechal, A Zou, L AF Marechal, Alexandre Zou, Lee TI DNA Damage Sensing by the ATM and ATR Kinases SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; REPLICATION PROTEIN-A; HOMOLOGOUS RECOMBINATION REPAIR; CELL-CYCLE CHECKPOINT; MAINTAINS GENOMIC STABILITY; EARLY EMBRYONIC LETHALITY; S-PHASE CHECKPOINT; C-TERMINAL TAIL; ATAXIA-TELANGIECTASIA; MRE11-RAD50-NBS1 COMPLEX AB In eukaryotic cells, maintenance of genomic stability relies on the coordinated action of a network of cellular processes, including DNA replication, DNA repair, cell-cycle progression, and others. The DNA damage response (DDR) signaling pathway orchestrated by the ATM and ATR kinases is the central regulator of this network in response to DNA damage. Both ATM and ATR are activated by DNA damage and DNA replication stress, but their DNA damage specificities are distinct and their functions are not redundant. Furthermore, ATM and ATR often work together to signal DNA damage and regulate downstream processes. Here, we will discuss the recent findings and current models of how ATM and ATR sense DNA damage, how they are activated by DNA damage, and how they function in concert to regulate the DDR. C1 [Marechal, Alexandre; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU Fonds de Recherche du Quebec-Sante (FRQS); NIH [GM076388] FX We are especially grateful to Dr. Stephen Elledge for his insightful comments on the manuscript. A.M. is supported by a postdoctoral fellowship from the Fonds de Recherche du Quebec-Sante (FRQS). L.Z. is a Jim and Ann Orr Massachusetts General Hospital Research Scholar and is supported by NIH grant GM076388. We apologize to colleagues whose work we could not discuss because of space constraints. NR 154 TC 17 Z9 18 U1 4 U2 25 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD SEP PY 2013 VL 5 IS 9 AR a012716 DI 10.1101/cshperspect.a012716 PG 17 WC Cell Biology SC Cell Biology GA 228EO UT WOS:000325168700005 ER PT J AU Bowles, DW Weickhardt, A Jimeno, A AF Bowles, D. W. Weickhardt, A. Jimeno, A. TI AFATINIB FOR THE TREATMENT OF PATIENTS WITH EGFR-POSITIVE NON-SMALL CELL LUNG CANCER SO DRUGS OF TODAY LA English DT Article DE Afatinib; EGFR; Non-small cell lung cancer; BIBW-2992; Dual inhibitor ID GROWTH-FACTOR RECEPTOR; ADVANCED SOLID TUMORS; ERBB FAMILY BLOCKER; TYROSINE KINASE INHIBITOR; METASTATIC BREAST-CANCER; I DOSE-ESCALATION; PHASE-I; OPEN-LABEL; ACQUIRED-RESISTANCE; BIBW 2992 AB Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are valuable treatments for EGFR-mutated non-small cell lung cancer (NSCLC). Anti-EGFR anti-bodies are widely used in the treatment of head and neck squamous cell carcinomas (HNSCC) and in KRAS wildtype colorectal cancer. The first-generation, reversible EGFR inhibitors erlotinib and gefitinib in the first-line setting provide superior progression-free survival and quality of life compared to conventional chemotherapy in NSCLC harboring activating EGFR mutations. However, these therapies eventually fail and new options are needed. Afatinib is a novel irreversible inhibitor of the ErbB family members EGFR, tyrosine kinase-type cell surface receptors HER2 and HER4. It shows preclinical efficacy in NSCLC with common EGFR-activating mutations and the T790M mutation typically associated with EGFR TKI resistance. Preclinical activity is seen in other tumor types as well, including HNSCC. Clinically, afatinib has been evaluated in the broad-reaching LUX Lung trial program, with significant activity seen in the first and later-line settings. It is also under investigation in multiple other tumor types. This review will stress on afatinib's preclinical pharmacology, pharmacokinetics and clinical activity with a focus on NSCLC. C1 [Bowles, D. W.; Jimeno, A.] Univ Colorado, Sch Med, Div Med Oncol, Denver, CO USA. [Bowles, D. W.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Weickhardt, A.] Austin Hosp, Olivia Newton John Canc & Wellness Ctr, Melbourne, Vic 3084, Australia. RP Jimeno, A (reprint author), Univ Colorado Denver, Div Med Oncol, 12801 East 17th Ave,MS 8117, Aurora, CO 80045 USA. EM antonio.jimeno@ucdenver.edu NR 73 TC 7 Z9 8 U1 0 U2 18 PU PROUS SCIENCE, SAU-THOMSON REUTERS PI BARCELONA PA 398 PROVENCA, 08025 BARCELONA, SPAIN SN 1699-3993 J9 DRUG TODAY JI Drugs Today PD SEP PY 2013 VL 49 IS 9 BP 523 EP 535 DI 10.1358/dot.2013.49.9.2016610 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225SO UT WOS:000324982800001 PM 24086949 ER PT J AU Daskalakis, NP Lehrner, A Yehuda, R AF Daskalakis, Nikolaos P. Lehrner, Amy Yehuda, Rachel TI Endocrine Aspects of Post-traumatic Stress Disorder and Implications for Diagnosis and Treatment SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article DE Stress; Sympathetic; Hypothalamic-pituitary-adrenal axis; Cortisol; Post-traumatic stress disorder ID GLUCOCORTICOID-RECEPTOR EXPRESSION; NATIONAL COMORBIDITY SURVEY; COMBAT VETERANS; RISK-FACTORS; LOW CORTISOL; HOLOCAUST SURVIVORS; MAJOR DEPRESSION; ANIMAL-MODEL; HPA AXIS; PTSD AB Post-traumatic stress disorder (PTSD) is a serious, multisystem disorder with multiple medical comorbidities. This article reviews the current literature on the endocrine aspects of PTSD, specifically hypothalamic-pituitary-adrenal axis alterations indicative of low cortisol and increased glucocorticoid sensitivity, and the proposed mechanisms whereby these alterations increase risk or reflect pathophysiology. Discussion includes novel treatment innovations and directions for future research. C1 [Daskalakis, Nikolaos P.; Lehrner, Amy; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. [Daskalakis, Nikolaos P.; Lehrner, Amy; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY 10029 USA. [Daskalakis, Nikolaos P.; Lehrner, Amy; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, PTSD Program, Mental Hlth Care Ctr, Bronx, NY 10468 USA. [Daskalakis, Nikolaos P.; Lehrner, Amy; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Lab Clin Neuroendocrinol & Neurochem, Bronx, NY 10468 USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Daskalakis, NP (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, Lab Mol Neuropsychiat, Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM nikolaos.daskalakis@mssm.edu RI Daskalakis, Nikolaos/B-7930-2014 OI Daskalakis, Nikolaos/0000-0003-1660-9112 NR 68 TC 38 Z9 42 U1 7 U2 34 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2013 VL 42 IS 3 BP 503 EP + DI 10.1016/j.ecl.2013.05.004 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228MO UT WOS:000325191100007 PM 24011883 ER PT J AU Miller, KK AF Miller, Karen Klahr TI Endocrine Effects of Anorexia Nervosa SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article DE Anorexia nervosa; Hypogonadism; Hypercortisolemia; Growth hormone; Osteoporosis ID BONE-MINERAL DENSITY; TRABECULAR STRUCTURE-ANALYSIS; HORMONE SECRETORY PATTERN; DWELLING ADOLESCENT GIRLS; PANEL VOLUME CT; GROWTH-HORMONE; PEPTIDE-YY; HYPOTHALAMIC AMENORRHEA; EATING-DISORDERS; YOUNG-WOMEN AB A key feature of anorexia nervosa, a disease primarily psychiatric in origin, is chronic starvation, which results in profound neuroendocrine dysregulation, including hypogonadism, relative growth hormone resistance, and hypercortisolemia. A recent area of investigation is appetite hormone dysregulation. Whether such dysregulation is compensatory or plays a role in the pathophysiology of anorexia nervosa is incompletely understood. The primary therapy for anorexia remains psychiatric, and endocrine abnormalities tend to improve with weight restoration, although residual endocrine dysfunction can occur. In addition, therapies directed at specific complications have been a particular focus of research. C1 [Miller, Karen Klahr] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Miller, Karen Klahr] Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B, Boston, MA 02114 USA. RP Miller, KK (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM kkmiller@partners.org FU NIH [R01 DK052625, R01 MH083657] FX Dr Miller has no relevant conflicts to disclose. This work was completed with the support of the following NIH grants: R01 DK052625 and R01 MH083657. NR 80 TC 7 Z9 7 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2013 VL 42 IS 3 BP 515 EP + DI 10.1016/j.ecl.2013.05.007 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228MO UT WOS:000325191100008 PM 24011884 ER PT J AU Dossett, ML Kohatsu, W Nunley, W Mehta, D Davis, RB Phillips, RS Yeh, G AF Dossett, Michelle L. Kohatsu, Wendy Nunley, William Mehta, Darshan Davis, Roger B. Phillips, Russell S. Yeh, Gloria TI A MEDICAL STUDENT ELECTIVE PROMOTING HUMANISM, COMMUNICATION SKILLS, COMPLEMENTARY AND ALTERNATIVE MEDICINE AND PHYSICIAN SELF-CARE: AN EVALUATION OF THE HEART PROGRAM SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Article DE Professionalism; humanism; communication skills; integrative medicine; self-care skills; medical education ID HIDDEN CURRICULUM; EMPATHY; PROFESSIONALISM; BURNOUT; NARRATIVES; ATTITUDES; EROSION AB Objective: In 2002 the American Medical Student Association (AMSA) created a fourth-year medical student elective known as the Humanistic Elective in alternative medicine, Activism, and Reflective Transformation (HEART) that provided the opportunity for students to explore humanism in medicine, self-care, complementary and alternative medicine modalities, communication, activism, and community building in a four-week immersion experience. The educational effects of this elective, and whether it has met its stated goals, are unknown. Method: The authors conducted a web-based, cross-sectional survey of the first eight cohorts of HEART graduates in 2010. Survey questions assessed respondents' demographics and perspectives on the educational impact of the elective. Descriptive statistics were used to characterize the sample and qualitative analyses were guided by grounded theory. Results: Of 168 eligible alumni, 122 (73%) completed the survey. The majority were female (70%), age <= 35 (77%) years, and trained in primary care specialties (66%). Half were attendings in practice. The majority of respondents felt the elective taught professionalism (89%) and communication skills (92%) well or very well. The majority highly agreed that the elective helped them better cope with stress during residency training (80%), taught them self-care skills (75%), and improved their ability to empathize and connect with patients (71%). Qualitative analysis of the personal and professional impact of the elective identified twelve common themes with self-discovery, self-care, and collegial development/community most frequently cited. Conclusions: The majority of HEART graduates endorse learning important skills and benefiting from the experience both personally and professionally. Aspects of the HEART curriculum may help training programs teach professionalism and improve trainee well-being. C1 [Dossett, Michelle L.; Davis, Roger B.; Phillips, Russell S.; Yeh, Gloria] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Dossett, Michelle L.; Mehta, Darshan; Davis, Roger B.; Phillips, Russell S.; Yeh, Gloria] Harvard Univ, Sch Med, Boston, MA USA. [Kohatsu, Wendy] Univ Calif San Francisco, Santa Rosa Family Med Residency, Santa Rosa, CA USA. [Nunley, William] CareOregon, Portland, OR USA. [Nunley, William] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Dossett, Michelle L.; Mehta, Darshan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Davis, Roger B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Dossett, ML (reprint author), 330 Brookline Ave,CO-215, Boston, MA 02215 USA. EM mdossett@bidmc.harvard.edu OI Mehta, Darshan/0000-0003-0457-4717 FU institutional National Research Service Award [T32AT000051]; Katherine Swan-Ginsberg Humanism in Medicine Fellowship; Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center FX Dr. Dossett was supported by an institutional National Research Service Award #T32AT000051, a Katherine Swan-Ginsberg Humanism in Medicine Fellowship, and by the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center. NR 28 TC 8 Z9 8 U1 2 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD SEP-OCT PY 2013 VL 9 IS 5 BP 292 EP 298 DI 10.1016/j.explore.2013.06.003 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 229XA UT WOS:000325300000007 PM 24021470 ER PT J AU Tanner, JB Tanner, SME Thapa, GB Chang, YC Watson, KLM Staunton, E Howarth, C Basnyat, B Harris, NS AF Tanner, John B. Tanner, Sarah M. E. Thapa, Ghan Bahadur Chang, Yuchiao Watson, Kirsty L. M. Staunton, Eamon Howarth, Claire Basnyat, Buddha Harris, N. Stuart TI A Randomized Trial of Temazepam versus Acetazolamide in High Altitude Sleep Disturbance SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE acetazolamide; altitude; hypoxia; sleep disorders; temazepam ID ACUTE MOUNTAIN-SICKNESS; SIMULATED ALTITUDE; ACTIGRAPHY; ZOLPIDEM; PERFORMANCE; VENTILATION; PATTERNS; ZALEPLON; QUALITY AB Tanner, John B., Sarah M.E. Tanner, Ghan Bahadur Thapa, Yuchiao Chang, Kirsty L.M. Watson, Eamon Staunton, Claire Howarth, Buddha Basnyat, and N. Stuart Harris. A randomized trial of temazepam versus acetazolamide in high-altitude sleep disturbance. High Alt Med Biol 14, 234-239, 2013.This study is the first comparative trial of sleep medications at high altitude. We performed a randomized, double-blind trial of temazepam and acetazolamide at an altitude of 3540 meters. 34 healthy trekkers with self-reports of high-altitude sleep disturbance were randomized to temazepam 7.5mg or acetazolamide 125mg taken at bedtime for one night. The primary outcome was sleep quality on a 100mm visual analog scale. Additional measurements were obtained with actigraphy; pulse oximetry; and questionnaire evaluation of sleep, daytime drowsiness, daytime sleepiness, and acute mountain sickness. Sixteen subjects were randomized to temazepam and 18 to acetazolamide. Sleep quality on the 100mm visual analog scale was higher for temazepam (59.6, SD 20.1) than acetazolamide (46.2, SD 20.2; p=0.048). Temazepam also demonstrated higher subjective sleep quality on the Groningen Sleep Quality Scale (3.5 vs. 6.8, p=0.009) and sleep depth visual analog scale (60.3 vs. 41.4, p=0.028). The acetazolamide group reported significantly more awakenings to urinate (1.8 vs. 0.5, p=0.007). No difference was found with regards to mean nocturnal oxygen saturation (84.1 vs. 84.4, p=0.57), proportion of the night spent in periodic breathing, relative desaturations, sleep onset latency, awakenings, wake after sleep onset, sleep efficiency, Stanford Sleepiness Scale scores, daytime drowsiness, or change in self-reported Lake Louise Acute Mountain Sickness scores. We conclude that, at current recommended dosing, treatment of high-altitude sleep disturbance with temazepam is associated with increased subjective sleep quality compared to acetazolamide. C1 [Tanner, John B.; Harris, N. Stuart] Massachusetts Gen Hosp, Dept Emergency Med, Div Wilderness Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tanner, Sarah M. E.; Staunton, Eamon; Howarth, Claire; Basnyat, Buddha] Himalayan Rescue Assoc, Kathmandu, Nepal. [Thapa, Ghan Bahadur] Mt Med Soc Nepal, Kathmandu, Nepal. [Watson, Kirsty L. M.] Royal Lancaster Infirm, Lancaster, England. RP Tanner, JB (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM john.barlow.tanner@gmail.com FU Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard University; Massachusetts General Hospital Department of Emergency Medicine FX This work was conducted with support from Harvard Catalyst. The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health.; This study was funded by the Massachusetts General Hospital Department of Emergency Medicine. NR 33 TC 4 Z9 4 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD SEP 1 PY 2013 VL 14 IS 3 BP 234 EP 239 DI 10.1089/ham.2013.1023 PG 6 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 223TV UT WOS:000324834700015 PM 24028643 ER PT J AU Cakmak, S Keklikci, K Sivrioglu, AK Rodop, O AF Cakmak, Selami Keklikci, Kenan Sivrioglu, Ali Kemal Rodop, Osman TI Intrathoracic displacement of the humeral head in a trauma patient SO INDIAN JOURNAL OF ORTHOPAEDICS LA English DT Letter C1 [Cakmak, Selami; Keklikci, Kenan; Rodop, Osman] GATA Haydarpasa Hosp, Dept Orthopaed & Traumatol, Istanbul, Turkey. [Sivrioglu, Ali Kemal] Aksaz Mil Hosp, Dept Radiol, Mugla, Turkey. RP Cakmak, S (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,Jackson 1206, Boston, MA 02114 USA. EM selamicakmak@gmail.com NR 3 TC 1 Z9 1 U1 0 U2 1 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0019-5413 J9 INDIAN J ORTHOP JI Indian J. Orthop. PD SEP-OCT PY 2013 VL 47 IS 5 BP 530 EP U112 DI 10.4103/0019-5413.118215 PG 2 WC Orthopedics SC Orthopedics GA 231FJ UT WOS:000325400200019 PM 24133318 ER PT J AU Thomas, WW Harvey, RJ Rudmik, L Hwang, PH Schlosser, RJ AF Thomas, W. Walsh, III Harvey, Richard J. Rudmik, Luke Hwang, Peter H. Schlosser, Rodney J. TI Distribution of topical agents to the paranasal sinuses: an evidence-based review with recommendations SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE sinusitis; topical; spray; irrigation; nebulizer; therapies; anatomy; surgery ID CLINICAL-PRACTICE GUIDELINES; NASAL IRRIGATION; MIDDLE MEATUS; HEAD POSITION; CHRONIC RHINOSINUSITIS; SINONASAL IRRIGATION; INTRANASAL DELIVERY; PULSATING AEROSOLS; CONTROLLED-TRIAL; NOSE DROPS AB BackgroundThe objective of this work was to review the literature concerning the distribution of topical therapeutics to the sinuses versus nasal cavity regarding: surgical state, delivery device, head position, and nasal anatomy and to provide evidence-based recommendations. MethodsA systematic review was conducted using Medline, EMBASE, and Cochrane databases to perform a Medical Subject Heading search of the literature from 1946 until the last week of May 2012. Articles were independently reviewed and graded for level of evidence. All authors came to consensus on recommendations through an iterative process. ResultsRecommendations were made for: improved sinus delivery with high-volume devices and after standard sinus surgery. Recommendations were made against low-volume delivery devices, such as drops, sprays, or simple nebulizers as they do not reliably reach the sinuses. If large-volume devices are not tolerated, low-volume devices are recommended using the lying head back or lateral head low positions to improve nasal cavity distribution to the middle meatus or olfactory cleft. ConclusionSurgery, volume of device, head position, and nasal anatomy were shown to impact distribution to the sinuses. Recommendations are made based upon this evidence as to how to best maximize therapeutic distribution to the sinuses. C1 [Thomas, W. Walsh, III; Schlosser, Rodney J.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29403 USA. [Thomas, W. Walsh, III; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29403 USA. [Harvey, Richard J.] Univ New S Wales, Div Rhinol & Endoscop Skull Base Surg, Sydney, NSW, Australia. [Harvey, Richard J.] St Vincents Hosp, Sydney, NSW 2010, Australia. [Rudmik, Luke] Univ Calgary, Div Otolaryngol Head & Neck Surg, Calgary, AB T2N 1N4, Canada. [Hwang, Peter H.] Stanford Univ, Dept Otolaryngol Head & Neck Surg, Palo Alto, CA 94304 USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29403 USA. EM schlossr@musc.edu NR 42 TC 28 Z9 28 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD SEP PY 2013 VL 3 IS 9 BP 691 EP 703 DI 10.1002/alr.21172 PG 13 WC Otorhinolaryngology SC Otorhinolaryngology GA 227KL UT WOS:000325111500002 PM 23729216 ER PT J AU Sedaghat, AR Gray, ST Chambers, KJ Wilke, CO Caradonna, DS AF Sedaghat, Ahmad R. Gray, Stacey T. Chambers, Kyle J. Wilke, Claus O. Caradonna, David S. TI Sinonasal anatomic variants and asthma are associated with faster development of chronic rhinosinusitis in patients with allergic rhinitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE allergic rhinitis; chronic rhinosinusitis; computed tomography; infraorbital cell; Haller cell; frontal intersinus cell; asthma ID ENDOSCOPIC SINUS SURGERY; PATHOPHYSIOLOGY; EPIDEMIOLOGY; INFLAMMATION; REFLUX; IMPACT; CT AB BackgroundAllergic rhinitis (AR) and chronic rhinosinusitis (CRS) are a major burden to the healthcare system. Although no causal relationship has been established, previous work has demonstrated a strong association of AR with CRS. In this study, we sought to identify risk factors that may influence speed of development of CRS in patients with AR. MethodsRetrospective review of all patients diagnosed with AR without CRS presenting to an otolaryngology clinic at a tertiary medical center as part of a multidisciplinary allergy evaluation between March 2004 and November 2011. Medical records were evaluated for clinicodemographic factors including age, gender, smoking history, medical comorbidities, categories of AR based on formal allergy testing, the presence of sinonasal anatomic variants on computed tomography as well as subsequent development of CRS. ResultsFaster progression to CRS in patients with AR was associated with comorbid asthma (hazard ratio [HR] = 3.97) as well as sinonasal anatomic variants, such as infraorbital cells (HR = 7.39), and frontal intersinus cells (HR = 68.03), on multivariate survival analysis. A statistically significant but negative interaction between infraorbital cells and frontal intersinus cells suggests that concomitant presence of both leads to a less than additive increase in the rate of CRS progression. ConclusionSinonasal anatomical variants, infraorbital cells, and frontal intersinus cells, as well as comorbid asthma are associated with faster development of CRS in patients with AR. The presence of these clinical risk factors identifies patients who should be counseled on compliance with medical therapy for AR. C1 [Sedaghat, Ahmad R.; Gray, Stacey T.; Chambers, Kyle J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Chambers, Kyle J.; Caradonna, David S.] Beth Israel Deaconess Med Ctr, Div Otolaryngol, Boston, MA 02215 USA. [Sedaghat, Ahmad R.; Gray, Stacey T.; Chambers, Kyle J.; Caradonna, David S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Wilke, Claus O.] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA. [Wilke, Claus O.] Univ Texas Austin, Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu RI Wilke, Claus/B-4643-2008 OI Wilke, Claus/0000-0002-7470-9261 NR 25 TC 16 Z9 17 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD SEP PY 2013 VL 3 IS 9 BP 755 EP 761 DI 10.1002/alr.21163 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 227KL UT WOS:000325111500012 PM 23504927 ER PT J AU Garone, C Donati, MA Sacchini, M Garcia-Diaz, B Bruno, C Calvo, S Mootha, VK DiMauro, S AF Garone, Caterina Donati, Maria Alice Sacchini, Michele Garcia-Diaz, Beatriz Bruno, Claudio Calvo, Sarah Mootha, Vamsi K. DiMauro, Salvatore TI Mitochondrial Encephalomyopathy Due to a Novel Mutation in ACAD9 SO JAMA NEUROLOGY LA English DT Article ID COMPLEX I DEFICIENCY; GENES AB IMPORTANCE Mendelian forms of complex I deficiency are usually associated with fatal infantile encephalomyopathy. Application of "MitoExome" sequencing (deep sequencing of the entire mitochondrial genome and the coding exons of >1000 nuclear genes encoding the mitochondrial proteome) allowed us to reveal an unusual clinical variant of complex I deficiency due to a novel homozygous mutation in ACAD9. The patient had an infantile-onset but slowly progressive encephalomyopathy and responded favorably to riboflavin therapy. OBSERVATION A 13-year-old boy had exercise intolerance, weakness, and mild psychomotor delay. Muscle histochemistry showed mitochondrial proliferation, and biochemical analysis revealed severe complex I deficiency (15% of normal). The level of complex I holoprotein was reduced as determined by use ofWestern blot both in muscle (54%) and in fibroblasts (57%). CONCLUSIONS AND RELEVANCE The clinical presentation of complex I deficiency due ACAD9 mutations spans from fatal infantile encephalocardiomyopathy to mild encephalomyopathy. Our data support the notion that ACAD9 functions as a complex I assembly protein. ACAD9 is a flavin adenine dinucleotide-containing flavoprotein, and treatment with riboflavin is advisable. C1 [Garone, Caterina; Garcia-Diaz, Beatriz; DiMauro, Salvatore] Columbia Univ, Med Ctr, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Garone, Caterina] Univ Turin, Joint PhD Program, I-10124 Turin, Italy. [Garone, Caterina] Univ Bologna, I-40126 Bologna, Italy. [Donati, Maria Alice; Sacchini, Michele] Univ Florence, Meyer Childrens Hosp, Dept Pediat, Metab & Muscular Unit, I-50121 Florence, Italy. [Bruno, Claudio] Gaslini Inst, IRCCS G, Unit Muscular & Neurodegenerat Dis, Genoa, Italy. [Calvo, Sarah; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Calvo, Sarah; Mootha, Vamsi K.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Calvo, Sarah; Mootha, Vamsi K.] MIT, Cambridge, MA 02139 USA. RP DiMauro, S (reprint author), Columbia Univ, Med Ctr, Coll Phys & Surg, Dept Neurol, 630 W 168th St,Room 4-424B, New York, NY 10032 USA. EM sd12@columbia.edu RI Bruno, Claudio/A-3148-2015; OI Bruno, Claudio/0000-0002-3426-2901; Garone, Caterina/0000-0003-4928-1037 FU National Institutes of Health [HD032062]; Italian Congenital Metabolic Disorders Association; Marriott Mitochondrial Disorders Clinical Research Fund FX Dr DiMauro receives compensation as a member of the editorial board of MedLink Neurology.; This work has been supported by the National Institutes of Health (grant HD032062), the Italian Congenital Metabolic Disorders Association, and the Marriott Mitochondrial Disorders Clinical Research Fund. NR 10 TC 11 Z9 12 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD SEP PY 2013 VL 70 IS 9 BP 1177 EP 1179 DI 10.1001/jamaneurol.2013.3197 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 228TB UT WOS:000325211600015 PM 23836383 ER PT J AU Codd, PJ Agarwalla, PK Berry-Candelario, J Nahed, BV AF Codd, Patrick J. Agarwalla, Pankaj K. Berry-Candelario, John Nahed, Brian V. TI Kernohan-Woltman Notch Phenomenon in Acute Subdural Hematoma SO JAMA NEUROLOGY LA English DT Editorial Material ID CONTRALATERAL BRAIN-TUMOR; INCISURA; CRUS C1 [Codd, Patrick J.; Agarwalla, Pankaj K.; Berry-Candelario, John; Nahed, Brian V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Codd, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,Gray 502, Boston, MA 02114 USA. EM pcodd@partners.org NR 3 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 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD SEP PY 2013 VL 70 IS 9 BP 1194 EP 1195 DI 10.1001/2013.jamaneurol.54 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 228TB UT WOS:000325211600019 PM 23857229 ER PT J AU Hill, CA Ramakrishna, J Fracchia, MS Sternberg, D Ojha, S Infusino, S Hartnick, CJ AF Hill, Courtney A. Ramakrishna, Jyoti Fracchia, M. Shannon Sternberg, Daniel Ojha, Shilpa Infusino, Scott Hartnick, Christopher J. TI Prevalence of Eosinophilic Esophagitis in Children With Refractory Aerodigestive Symptoms SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ASSOCIATION AB IMPORTANCE Eosinophilic esophagitis (EoE) is an increasingly important diagnosis for children; it has a remarkable impact on their quality of life and can present with aerodigestive symptoms commonly evaluated by otolaryngologists. OBJECTIVES To evaluate the prevalence of EoE in children presenting to a pediatric aerodigestive clinic, to describe their presentation, and to review the role of subsequent food allergy evaluation and treatment. DESIGN Review of a prospective database. SETTING Tertiary pediatric multispecialty aerodigestive center. PATIENTS Children with aerodigestive symptoms refractory to medical treatment who underwent direct laryngoscopy with rigid or flexible bronchoscopy and esophagoscopy with or without pH probe study. MAIN OUTCOMES AND MEASURES Diagnosis of EoE. RESULTS Between 2003 and 2012, 376 of 1540 children seen in the center (mean [range] age, 4.54 [0-18.6] years; male to female ratio, 1.72:1) remained symptomatic despite medical therapy and thus underwent triple endoscopic evaluation. Of the 376 children, 14 (3.7%) were eventually diagnosed as having EoE, as defined by 15 or more eosinophils per high-power field on esophageal biopsy and either a negative pH study result or nonresponse to a trial of high-dose proton pump inhibitors. The subpopulation with EoE presented with airway symptoms and diagnoses, most commonly cough (n = 6; 42.9%). Inflammatory subglottic stenosis due to EoE was identified in 1 patient. Of the 14 children with EoE, 6 presented with gastrointestinal symptomatology, most commonly choking or gagging. Subsequent treatment including food allergy challenge and elimination diet resulted in a clinical improvement in half of the cases identified. CONCLUSIONS AND RELEVANCE This represents the largest multispecialty clinic epidemiologic study evaluating the prevalence of EoE in children presenting not strictly with gastrointestinal symptoms but rather with aerodigestive symptoms that are frequently evaluated by pediatric otolaryngologists. Although the prevalence is low, EoE should be considered for children with appropriate symptoms in whom other medical therapies fail. C1 [Hill, Courtney A.] Dartmouth Hitchcock Med Ctr, Otolaryngol Sect, Lebanon, NH 03766 USA. [Ramakrishna, Jyoti; Fracchia, M. Shannon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sternberg, Daniel; Ojha, Shilpa; Infusino, Scott; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Div Pediat Otolaryngol, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 11 TC 6 Z9 8 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD SEP PY 2013 VL 139 IS 9 BP 903 EP 906 DI 10.1001/jamaoto.2013.4171 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 228IZ UT WOS:000325180700004 PM 24051745 ER PT J AU Knoechel, B Lohr, JG AF Knoechel, Birgit Lohr, Jens G. TI Genomics of lymphoid malignancies reveal major activation pathways in lymphocytes SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Autoimmunity; Lymphoid malignancies; Somatic mutations ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-CELL LYMPHOMA; REGULATORY T-CELLS; BET BROMODOMAIN INHIBITION; MIXED-LINEAGE LEUKEMIA; REPRESSIVE COMPLEX 2; DNA METHYLATION; GENE-EXPRESSION AB Breakdown of tolerance leads to autoimmunity due to emergence of autoreactive T or B cell clones. Autoimmune diseases predispose to lymphoid malignancies and lymphoid malignancies, conversely, can manifest as autoimmune diseases. While it has been clear for a long time that a competitive advantage and uncontrolled growth of lymphocytes contribute to the pathogenesis of both lymphoid malignancies as well as autoimmune diseases, the overlap of the underlying mechanisms has been less well described. Next generation sequencing has led to massive expansion of the available genomic data in many diseases over the last five years. These data allow for comparison of the molecular pathogenesis between autoimmune diseases and lymphoid malignancies. Here, we review the similarities between autoimmune diseases and lymphoid malignancies: 1) Both, autoimmune diseases and lymphoid malignancies are characterized by activation of the same T and B cell signaling pathways, and dysregulation of these pathways can occur through genetic or epigenetic events. 2) In both scenarios, clonal and subclonal evolution of lymphocytes contribute to disease. 3) Development of both diseases not only depends on T or B cell intrinsic factors, such as germline or somatic mutations, but also on environmental factors. These include infections, the presence of other immune cells in the microenvironment, and the cytokine milieu. A better mechanistic understanding of the parallels between lymphomagenesis and autoimmunity may help the development of precision treatment strategies with rationally designed therapeutic agents. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Knoechel, Birgit] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Knoechel, Birgit] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Knoechel, Birgit] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Knoechel, Birgit; Lohr, Jens G.] Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA. [Knoechel, Birgit] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Knoechel, Birgit] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Knoechel, Birgit] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lohr, Jens G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Lohr, JG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM jlohr@partners.org FU NHLBI NIH HHS [T32 HL007574] NR 140 TC 2 Z9 2 U1 1 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD SEP PY 2013 VL 45 BP 15 EP 23 DI 10.1016/j.jaut.2013.06.012 PG 9 WC Immunology SC Immunology GA 231WH UT WOS:000325448600003 PM 23880067 ER PT J AU Pillai, S AF Pillai, Shiv TI Rethinking mechanisms of autoimmune pathogenesis SO JOURNAL OF AUTOIMMUNITY LA English DT Review DE Autoimmunity; Epigenetics; Genetic variants; Microbiome; SIAE ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-CELL ACTIVATION; LYMPHOID TYROSINE PHOSPHATASE; RHEUMATOID-ARTHRITIS; CD22-DEFICIENT MICE; INDEPENDENT RESPONSES; INHIBITORY RECEPTOR; NEGATIVE REGULATOR; DIABETES-MELLITUS; ADHESION MOLECULE AB Why exactly some individuals develop autoimmune disorders remains unclear. The broadly accepted paradigm is that genetic susceptibility results in some break in immunological tolerance, may enhance the availability of autoantigens, and may enhance inflammatory responses. Some environmental insults that occur on this background of susceptibility may then contribute to autoimmunity. In this review we discuss some aspects related to inhibitory signaling and rare genetic variants, as well as additional factors that might contribute to autoimmunity including the possible role of clonal somatic mutations, the role of epigenetic events and the contribution of the intestinal microbiome. Genetic susceptibility alleles generally contribute to the loss of immunological tolerance, the increased availability of autoantigens, or an increase in inflammation. Apart from common genetic variants, rare loss-of-function genetic variants may also contribute to the pathogenesis of autoimmunity. Studies of an inhibitory signaling pathway in B cells helped identify a negative regulatory enzyme called sialic acid acetyl esterase. The study of rare genetic variants of this enzyme provides an illustrative example showing the importance of detailed functional analyses of variant alleles and the need to exclude functionally normal common or rare genetic variants from analysis. It has also become clear that pathways that are functionally impacted by either common or rare defective variants can also be more significantly compromised by gene expression changes that may result from epigenetic alterations. Another important and evolving area that has been discussed relates to the role of the intestinal microbiome in influencing helper T cell polarization and the development of autoimmunity. (C) 2013 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Boston, MA 02129 USA. RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NIAID NIH HHS [R01 AI076505, R01 AI064930] NR 82 TC 38 Z9 39 U1 4 U2 34 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD SEP PY 2013 VL 45 BP 97 EP 103 DI 10.1016/j.jaut.2013.05.003 PG 7 WC Immunology SC Immunology GA 231WH UT WOS:000325448600012 PM 23809879 ER PT J AU Jenkins, AJ Yu, J Alaupovic, P Basu, A Klein, RL Lopes-Virella, M Baker, NL Hunt, KJ Lackland, DT Garvey, WT Lyons, TJ AF Jenkins, Alicia J. Yu, Jeremy Alaupovic, Petar Basu, Arpita Klein, Richard L. Lopes-Virella, Maria Baker, Nathaniel L. Hunt, Kelly J. Lackland, Daniel T. Garvey, W. Timothy Lyons, Timothy J. CA DCCT EDIC Res Grp TI Apolipoprotein-defined lipoproteins and apolipoproteins: Associations with abnormal albuminuria in type 1 diabetes in the diabetes control and complications trial/epidemiology of diabetes interventions and complications cohort SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Type 1 diabetes; Nephropathy; Albuminuria; Lipoproteins; Apolipoproteins ID CARDIOVASCULAR RISK-FACTOR; B-CONTAINING LIPOPROTEINS; VASCULAR-DISEASE RISK; DCCT/EDIC COHORT; RENAL-INSUFFICIENCY; INSULIN-RESISTANCE; C-III; DENSITY-LIPOPROTEIN; CENTRAL OBESITY; NEPHROPATHY AB Aims: Dyslipoproteinemia has been associated with nephropathy in diabetes, with stronger correlations in men than in women. We aimed to characterize and compare plasma lipoprotein profiles associated with normal and increased albuminuria in men and women using apolipoprotein-defined lipoprotein subclasses and simple apolipoprotein measures. Methods: This is a cross-sectional study in a subset (154 women and 282 men) of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, using samples obtained in 1997-9. Immunochemical methods were used to quantify plasma apolipoprotein-based lipoprotein subclasses and individual apolipoprotein levels. Results: In adjusted analyses, elevated Lipoprotein-B (Lp-B) was significantly associated with macroalbuminuria in men [odds ratios (OR) and 95% confidence interval (CI): 2.13 (1.15-3.97)] and women [3.01 (1.11-8.12)], while association with Lp-B:C was observed only in men [1.84 (1.19-2.86)]. For individual apolipoproteins the following significant associations with macroalbuminuria were observed in men only: Apolipoprotein B (ApoB) [1.97 (1.20-3.25)], Apo-AII [0.52 (0.29-0.93)], ApoC-III [1.95 (1.16-3.30)], "ApoC-III in VLDL" (heparin-manganese precipitate) [1.88 (1.16-3.04)1, and "ApoCIII in HDL" (heparin-manganese supernatant) [2.03 (1.27-3.26)], all P < 0.05). Conclusions: Atherogenic apolipoprotein-based profiles are associated with nephropathy in Type 1 diabetic men and to a lesser extent in women. The difference could result from the greater prevalence and severity of dyslipoproteinemia, and from the greater prevalence of renal dysfunction, in men vs women. (C) 2013 Elsevier Inc. All rights reserved. C1 [Jenkins, Alicia J.; Yu, Jeremy; Lyons, Timothy J.] Univ Oklahoma, Harold Hamm Diabet Ctr, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Jenkins, Alicia J.; Yu, Jeremy; Lyons, Timothy J.] Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK 73104 USA. [Alaupovic, Petar] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Basu, Arpita] Oklahoma State Univ, Dept Nutr Sci, Stillwater, OK 74078 USA. [Klein, Richard L.; Lopes-Virella, Maria] Med Univ S Carolina, Div Endocrinol, Charleston, SC 29425 USA. [Klein, Richard L.; Lopes-Virella, Maria] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Baker, Nathaniel L.; Hunt, Kelly J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Lackland, Daniel T.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr, Birmingham, AL 35294 USA. RP Lyons, TJ (reprint author), Harold Hamm Diabet Ctr, 1000 North Lincoln Blvd,Suite 2900, Oklahoma City, OK 73104 USA. EM t.lyons@qub.ac.uk FU American Diabetes Association, the National Institutes of Health NIH [PO1 HL55782]; Juvenile Diabetes Research Foundation [4-1998-272, 996001, 197028]; Diabetes Research and Wellness Foundation, Inc. (Fairfax, Virginia); Presbyterian Health Foundation of Oklahoma City; Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH (NCRR) [M01-RR-1070, M01 RR-14467]; OUHSC; Genentech, Inc.; NIDDK FX Grants were provided by: the American Diabetes Association, the National Institutes of Health NIH (PO1 HL55782), Juvenile Diabetes Research Foundation (# 4-1998-272, 996001, and 197028), the Diabetes Research and Wellness Foundation, Inc. (Fairfax, Virginia), and the Presbyterian Health Foundation of Oklahoma City. The DCCT/EDIC is sponsored through research contracts from the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Additional support was provided by the NIH (NCRR) Grants M01-RR-1070 and M01 RR-14467 to the General Clinical Research Centers at MUSC and OUHSC, and by Genentech, Inc. through a Cooperative Research and Development Agreement with the NIDDK. NR 48 TC 2 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD SEP-OCT PY 2013 VL 27 IS 5 BP 447 EP 453 DI 10.1016/j.jdiacomp.2013.06.002 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 229WX UT WOS:000325299700007 PM 23850262 ER PT J AU Henry, RR Chilton, R Garvey, WT AF Henry, Robert R. Chilton, Robert Garvey, W. Timothy TI New options for the treatment of obesity and type 2 diabetes mellitus (narrative review) SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Review DE Phentermine; Topiramate extended-release; Obesity; Type 2 diabetes; Cardiovascular ID CARDIOVASCULAR RISK-FACTORS; CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTION; HIGH BLOOD-PRESSURE; BODY-MASS INDEX; FREE FATTY-ACID; WEIGHT-LOSS; INSULIN-RESISTANCE; BARIATRIC SURGERY AB Moderate weight loss (>5%), which has been associated with improvements in glycemic parameters in patients with dysglycemia, also reduces the presence of other comorbidities, including dyslipidemia and hypertension, culminating in a reduced risk of cardiovascular disease. Lifestyle changes are the recommended preliminary approach to weight loss, with an initial weight-loss goal of 10% of body weight achieved over 6 months at a rate of 1-2 pounds per week selected as an appropriate target to decrease the severity of obesity-related risk factors. Implementing and maintaining the lifestyle changes associated with weight loss can, however, be challenging for many patients. Therefore, additional interventions sometimes may be necessary. Bariatric surgery can also be a highly effective option for weight loss and comorbidity reduction, but surgery carries considerable risks and is still applicable only to selected patients with type 2 diabetes. Thus, attention is turning to the use of weight-loss medications, including 2 recently approved compounds: twice-daily lorcaserin and a once-daily combination of phentermine and topiramate extended-release, both shown to be safe and effective therapies in the management of obesity in patients with type 2 diabetes. (C) 2013 Elsevier Inc. All rights reserved. C1 [Henry, Robert R.] VA San Diego Healthcare Syst, Ctr Metab Res, San Diego, CA USA. [Henry, Robert R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Chilton, Robert] Cardiovasc Dis & Intervent Cardiol Univ Hosp, San Antonio, TX USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. RP Henry, RR (reprint author), VA San Diego Healthcare Syst, Ctr Metab Res, San Diego, CA USA. EM rrhenry@vapop.ucsd.edu FU VIVUS, Inc. FX We would like to acknowledge and thank The Lockwood Group for editorial assistance (funding was provided by VIVUS, Inc.), and VIVUS, Inc. internal contributors. NR 66 TC 14 Z9 16 U1 2 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD SEP-OCT PY 2013 VL 27 IS 5 BP 508 EP 518 DI 10.1016/j.jdiacomp.2013.04.011 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 229WX UT WOS:000325299700017 PM 23726071 ER PT J AU Iwaki, S Bonmassar, G Belliveau, JW AF Iwaki, Sunao Bonmassar, Giorgio Belliveau, John W. TI Dynamic cortical activity during the perception of three-dimensional object shape from two-dimensional random-dot motion SO JOURNAL OF INTEGRATIVE NEUROSCIENCE LA English DT Article DE MEG-fMRI integration; 3D structure perception from motion (3D SFM); Granger causality; effective connectivity; dorsal visual system; ventral visual system ID STRUCTURE-FROM-MOTION; SURFACE-BASED ANALYSIS; COORDINATE SYSTEM; DEPTH-PERCEPTION; GLOBAL MOTION; HUMAN BRAIN; FMRI; CORTEX; MAGNETOENCEPHALOGRAPHY; DISSOCIATION AB Recent neuroimaging studies implicate that both the dorsal and ventral visual pathways, as well as the middle temporal (MT) areas which are critical for the perception of visual motion, are involved in the perception of three-dimensional (3D) structure from two-dimensional (2D) motion (3D-SFM). However, the neural dynamics underlying the reconstruction of a 3D object from 2D optic flow is not known. Here we combined magnetoencephalography (MEG) and functional MRI (fMRI) measurements to investigate the spatiotemporal brain dynamics during 3D-SFM. We manipulated parametrically the coherence of randomly moving groups of dots to create different levels of 3D perception and to study the associated changes in brain activity. At different latencies, the posterior infero-temporal (pIT), the parieto-occipital (PO), and the intraparietal (IP) regions showed increased neural activity during highly coherent motion conditions in which subjects perceived a robust 3D object. Causality analysis between these regions indicated significant causal influence from IP to pIT and from pIT to PO only in conditions where subjects perceived a robust 3D object. Current results suggest that the perception of a 3D object from 2D motion includes integration of global motion and 3D mental image processing, as well as object recognition that are accomplished by interactions between the dorsal and ventral visual pathways. C1 [Iwaki, Sunao] Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, Tsukuba, Ibaraki 3058566, Japan. [Iwaki, Sunao; Bonmassar, Giorgio; Belliveau, John W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Iwaki, S (reprint author), Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, Tsukuba, Ibaraki 3058566, Japan. EM s.iwaki@aist.go.jp RI Iwaki, Sunao/B-1079-2011 OI Iwaki, Sunao/0000-0002-7123-7203 FU NICHD NIH HHS [R01 HD040712]; NINDS NIH HHS [R01 NS037462] NR 38 TC 2 Z9 3 U1 0 U2 8 PU IMPERIAL COLLEGE PRESS PI LONDON PA 57 SHELTON ST, COVENT GARDEN, LONDON WC2H 9HE, ENGLAND SN 0219-6352 J9 J INTEGR NEUROSCI JI J. Integr. Neurosci. PD SEP PY 2013 VL 12 IS 3 BP 355 EP 367 DI 10.1142/S0219635213500210 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 229PI UT WOS:000325279000004 PM 24070059 ER PT J AU Scheib, SA Jones, HH Boruta, DM Simpson, K Bedaiwy, M Grumbine, FC Fader, AN AF Scheib, Stacey A. Jones, Howard H. Boruta, David M. Simpson, Khara Bedaiwy, Mohamed Grumbine, Francis C. Fader, Amanda N. TI Laparoendoscopic Single-Site Surgery for Management of Adnexal Masses in Pregnancy: Case Series SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Adnexal mass; Laparoscopic single-site surgery; Pregnancy; Single Port Laparoscopy ID LAPAROSCOPIC CHOLECYSTECTOMY; OVARIAN-TUMORS; LAPAROTOMY; RISK; CHOLELITHIASIS; COMPLICATIONS; APPENDICITIS; OUTCOMES; HERNIA AB The incidence of adnexal masses in pregnancy is estimated to be 1% to 4%. In select cases, surgical intervention is required. Recent studies have demonstrated that laparoscopy during pregnancy is safe and confers many advantages over laparotomy. Herein we present a series of nine cases collected prospectively that demonstrate the feasibility, safety, and putative benefits of laparoendoscopic single-site surgery for treatment of adnexal masses in pregnant women. Journal of Minimally Invasive Gynecology (2013) 20, 701-707 (C) 2013 AAGL. All rights reserved. C1 [Scheib, Stacey A.; Simpson, Khara; Fader, Amanda N.] Johns Hopkins Med Inst, Baltimore, MD USA. [Jones, Howard H.] Vanderbilt Univ, Nashville, TN 37235 USA. [Boruta, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bedaiwy, Mohamed] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Simpson, Khara; Grumbine, Francis C.; Fader, Amanda N.] Greater Baltimore Med Ctr, Baltimore, MD USA. RP Scheib, SA (reprint author), Johns Hopkins Med Inst, 600 N Wolfe St,Ste 246, Baltimore, MD USA. EM sscheib1@jhmi.edu NR 37 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD SEP-OCT PY 2013 VL 20 IS 5 BP 701 EP 707 DI 10.1016/j.jmig.2013.02.024 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 229WY UT WOS:000325299800029 PM 24034540 ER PT J AU Erickson, JI AF Erickson, Jeanette Ives TI A Chief Nurse's Reflections on Marathon Monday 2013 SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Erickson, JI (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jiveserickson@partners.org NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD SEP PY 2013 VL 43 IS 9 BP 429 EP 430 DI 10.1097/NNA.0b013e3182a23aa3 PG 2 WC Nursing SC Nursing GA 219QA UT WOS:000324521900001 PM 23979030 ER PT J AU Cho, CH Seo, HJ Bae, KC Lee, KJ Hwang, I Warner, JJP AF Cho, Chul-Hyun Seo, Hyuk-Jun Bae, Ki-Cheor Lee, Kyung-Jae Hwang, Ilseon Warner, Jon J. P. TI The impact of depression and anxiety on self-assessed pain, disability, and quality of life in patients scheduled for rotator cuff repair SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Rotator cuff; psychological distress; depression; anxiety; pain; functional disability; quality of life ID PROGNOSTIC-FACTORS; SHOULDER FUNCTION; KNEE REPLACEMENT; HEALTH-STATUS; WHOQOL-BREF; TEARS; OUTCOMES; MULTIPRACTICE; COMORBIDITY; DISORDERS AB Background: Psychological status may be an important predictor of outcome and patient satisfaction after treatment for rotator cuff disease. Few prior studies have considered these factors. The objective of the study was to investigate the prevalence of psychological distress and its effect on self-assessed pain, disability, and health-related quality of life in patients scheduled for rotator cuff repair. Materials and methods: We assessed 107 consecutive patients preoperatively using the Hospital Anxiety and Depression Scale (HADS); visual analog scale pain score; American Shoulder and Elbow Surgeons (ASES) scale; Korean Shoulder Scale (KSS); and World Health Organization Quality of Life Scale, Abbreviated Version (WHOQOL-BREF). Preoperative demographic, clinical, and radiologic parameters were also evaluated. Results: Of the patients, 28 (26.2%) had depression and 25 (23.4%) had anxiety. The HADS depression score was positively correlated with the visual analog scale pain score (P=.048) and negatively correlated with the ASES, KSS, and WHOQOL-BREF scores (P=.005, P=.004, and P<.0001, respectively). The HADS anxiety score was negatively correlated with the ASES, KSS, and WHOQOL-BREF scores (P=.034, P=.037, and P<.0001, respectively). On multivariate analysis with a linear regression model, the HADS depression score was an independent predictor of ASES, KSS, and WHOQOL-BREF scores (P=.02, P=.005, and P=.001, respectively). Conclusion: Depression and anxiety had a negative impact on self-assessed outcome measurements in patients scheduled for rotator cuff repair. Depression was a strong predictor of functional disability and health-related quality of life. Our results suggest that preoperative psychological status may influence postoperative outcome after rotator cuff repair and thus is an essential part of preoperative assessment. Level of evidence: Level I, Prospective Cohort, Prognosis Study. Crown Copyright (C) 2013 Published by Elsevier Ltd on behalf of Neonatal Nurses Association. All rights reserved. C1 [Cho, Chul-Hyun; Seo, Hyuk-Jun; Bae, Ki-Cheor; Lee, Kyung-Jae] Keimyung Univ, Sch Med, Dongsan Med Ctr, Dept Orthoped Surg,Pain Res Ctr, Taegu 700712, South Korea. [Hwang, Ilseon] Keimyung Univ, Sch Med, Dongsan Med Ctr, Dept Pathol, Taegu 700712, South Korea. [Warner, Jon J. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Shoulder Serv, Boston, MA USA. RP Cho, CH (reprint author), Keimyung Univ, Sch Med, Dongsan Med Ctr, Dept Orthoped Surg, 56 Dalseong Ro, Taegu 700712, South Korea. EM oscho5362@dsmc.or.kr OI Hwang, Ilseon/0000-0002-6122-4417; Cho, Chul-Hyun/0000-0003-0252-8741 NR 38 TC 23 Z9 24 U1 1 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP PY 2013 VL 22 IS 9 BP 1160 EP 1166 DI 10.1016/j.jse.2013.02.006 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 221GX UT WOS:000324647100008 PM 23594716 ER PT J AU Erickson, CS Barlow, AJ Pierre, JF Heneghan, AF Epstein, ML Kudsk, KA Gosain, A AF Erickson, Christopher S. Barlow, Amanda J. Pierre, Joseph F. Heneghan, Aaron F. Epstein, Miles L. Kudsk, Kenneth A. Gosain, Ankush TI Colonic enteric nervous system analysis during parenteral nutrition SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Enteric nervous system; nNOS; Neurotransmitter; Motility; TPN; Parenteral nutrition; Bombesin ID MOUSE MODEL; HIRSCHSPRUNGS-DISEASE; BARRIER FUNCTION; NEUROTRANSMITTER EXPRESSION; GASTROINTESTINAL-TRACT; LYMPHOID-TISSUE; BOMBESIN; MOTILITY; MICE; IMMUNITY AB Introduction: Parenteral nutrition (PN) is a necessary therapy used to feed patients with gastrointestinal dysfunction. Unfortunately, PN results in intestinal atrophy and changes to host immune function. PN may also induce additional effects on gut motility that we hypothesized would result from changes in the enteric nervous system. Methods: Mice received an intravenous (IV) catheter and were randomized to chow (n = 5), IV PN (n = 6), or IV PN + bombesin (BBS, 15 mu g/kg, 3 x/d) (n = 6) for 5 d. Colons were removed and dissected to measure the length and circumference. Enteric neuronal density and neurotransmitter expression were determined by co-immunostaining whole-mount tissue with Hu and neuronal nitric oxide synthase (nNOS). Results: The number of myenteric neurons expressing Hu and nNOS increased per unit length in the mid-colon during PN treatment compared with chow. This increase was abrogated by the addition of BBS to the PN regimen. However, the percentage of nNOS-expressing neurons was not significantly altered by PN. Morphometric analysis revealed a decrease in the length and circumference of the colon during PN administration that was partially normalized by supplementation of PN with BBS. A significant reduction in total fecal output was observed in PN animals compared with chow and was increased by mice receiving BBS in addition to PN. Conclusions: PN causes a constriction of the bowel wall, reducing not only the length but also the circumference of the colon. These changes cause a condensation of enteric neurons but no difference in neurotransmitter expression. BBS supplementation partially restores the constriction and increases the fecal output during PN treatment compared with PN treatment alone. (C) 2013 Elsevier Inc. All rights reserved. C1 [Erickson, Christopher S.; Epstein, Miles L.] Univ Wisconsin, Madison Sch Med & Publ Hlth, Dept Neurosci, Madison, WI 53792 USA. [Barlow, Amanda J.; Pierre, Joseph F.; Heneghan, Aaron F.; Kudsk, Kenneth A.; Gosain, Ankush] Univ Wisconsin, Madison Sch Med & Publ Hlth, Dept Surg, Madison, WI 53792 USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Gosain, A (reprint author), Univ Wisconsin, Dept Surg, 600 Highland Ave,K4-752 CSC, Madison, WI 53792 USA. EM gosain@surgery.wisc.edu FU Central Surgical Association Foundation Turcotte Award; NIH-NIDDK [RO1DK081634]; Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [I01BX001672] FX This research is supported by a Central Surgical Association Foundation Turcotte Award (AG), NIH-NIDDK RO1DK081634 grant (MLE), and grant I01BX001672 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (KAK). The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 27 TC 3 Z9 3 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2013 VL 184 IS 1 BP 132 EP 137 DI 10.1016/j.jss.2013.02.044 PG 6 WC Surgery SC Surgery GA 207NX UT WOS:000323609400022 PM 23601532 ER PT J AU Cheung, T Noecker, A McIntyre, CC Alterman, RL Tagliati, M AF Cheung, T. Noecker, A. McIntyre, C. C. Alterman, R. L. Tagliati, M. TI PRESENTATION: Modeling the Regions of Influence of Pallidal DBS for Dystonia. SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 27th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinson Disease and Other Movement Disorders CY OCT 01, 2013 CL PSG Symposium Comm, Montreal, CANADA SP PSG Funct Neurosurg & Hlth Care Outcomes & Disparities Working Grp HO PSG Symposium Comm C1 [Cheung, T.; Tagliati, M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Noecker, A.; McIntyre, C. C.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Alterman, R. L.] Beth Israel Deaconness Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2013 VL 28 IS 10 BP E1 EP E2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 224YV UT WOS:000324930300002 ER PT J AU Wong, JC Li, Y Schwarzschild, MA Ascherio, A Gao, X AF Wong, J. C. Li, Y. Schwarzschild, M. A. Ascherio, A. Gao, X. TI Restless legs syndrome: an early clinical feature of Parkinson's disease in men. SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 27th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinson Disease and Other Movement Disorders CY OCT 01, 2013 CL PSG Symposium Comm, Montreal, CANADA SP PSG Funct Neurosurg & Hlth Care Outcomes & Disparities Working Grp HO PSG Symposium Comm C1 [Wong, J. C.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Wong, J. C.; Schwarzschild, M. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wong, J. C.; Schwarzschild, M. A.; Ascherio, A.; Gao, X.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Y.; Ascherio, A.; Gao, X.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ascherio, A.; Gao, X.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2013 VL 28 IS 10 BP E5 EP E5 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 224YV UT WOS:000324930300013 ER PT J AU Gray, PJ Shipley, WU Efstathiou, JA AF Gray, Phillip J. Shipley, William U. Efstathiou, Jason A. TI T1 High-Grade Bladder Cancer Recurring After BCG Therapy: A Curative Alternative to Radical Cystectomy Exists SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BACILLUS-CALMETTE-GUERIN C1 [Gray, Phillip J.; Shipley, William U.; Efstathiou, Jason A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gray, Phillip J.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Cambridge, MA 02138 USA. RP Gray, PJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD SEP PY 2013 VL 27 IS 9 BP 873 EP + PG 2 WC Oncology SC Oncology GA 229CE UT WOS:000325238600008 PM 24282983 ER PT J AU Zuckerman, KE Mattox, K Donelan, K Batbayar, O Baghaee, A Bethell, C AF Zuckerman, Katharine E. Mattox, Kimber Donelan, Karen Batbayar, Oyundari Baghaee, Anita Bethell, Christina TI Pediatrician Identification of Latino Children at Risk for Autism Spectrum Disorder SO PEDIATRICS LA English DT Article DE autism spectrum disorder; Hispanic Americans; pediatrics; health care disparities; child development; developmental disabilities; developmental screening ID LIMITED ENGLISH PROFICIENCY; DEFICIT-HYPERACTIVITY DISORDER; HEALTH-CARE; ETHNIC DISPARITIES; YOUNG-CHILDREN; US CHILDREN; DEVELOPMENTAL-DISABILITIES; NATIONAL-SURVEY; SERVICES; DIAGNOSIS AB BACKGROUND AND OBJECTIVES: Latino-white disparities in age at autism spectrum disorder (ASD) diagnosis may be modified by primary care pediatrician (PCP) practices and beliefs. The objectives of this study were to assess ASD and developmental screening practices, attitudes toward ASD identification in Latino children, and barriers to ASD identification for Latino children, in a sample of 267 California PCPs. METHODS: In mail-based PCP survey, we assessed rates of bilingual general developmental and ASD screening, perceptions of parent ASD knowledge in Latino and white families, reports of difficulty assessing for ASDs in Latino and white children, and perceptions of barriers to early ASD identification for Latinos. RESULTS: Although 81% of PCPs offered some form of developmental screening, 29% of PCPs offered Spanish ASD screening per American Academy of Pediatrics guidelines, and only 10% offered both Spanish general developmental and Spanish ASD screening per American Academy of Pediatrics guidelines. Most PCPs thought that Latino (English and Spanish primary family language) parents were less knowledgeable about ASDs than white parents. PCPs had more difficulty assessing ASD risk for Latino children with Spanish primary family language than for white children, even when the PCP conducted recommended ASD screening or had > 25% Latino patients. The most frequent barrier to ASD identification in Latinos was access to developmental specialists. CONCLUSIONS: Multiple factors in the primary care setting may contribute to delayed ASD identification for Latinos. Promoting language-appropriate screening, disseminating culturally appropriate ASD materials to Latino families, improving the specialist workforce, and providing PCP support in screening and referral of Latino children may be important ways to reduce racial and ethnic differences in care. C1 [Zuckerman, Katharine E.; Mattox, Kimber; Batbayar, Oyundari; Baghaee, Anita; Bethell, Christina] Oregon Hlth & Sci Univ, Child & Adolescent Hlth Measurement Initiat, Portland, OR 97239 USA. [Zuckerman, Katharine E.; Mattox, Kimber] Oregon Hlth & Sci Univ, Div Gen Pediat, Portland, OR 97239 USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Zuckerman, KE (reprint author), Oregon Hlth & Sci Univ, 707 SW Gaines Rd,Mail Code CDRC P, Portland, OR 97239 USA. EM zuckerma@ohsu.edu FU Academic Pediatric Association/Commonwealth Fund Young Investigator Award; National Institute of Mental Health [1K23MH095828]; National Institutes of Health (NIH) FX This project was funded by an Academic Pediatric Association/Commonwealth Fund Young Investigator Award (principal investigator, Dr Zuckerman). Dr Zuckerman's effort was partially funded by grant 1K23MH095828 from the National Institute of Mental Health. Funded by the National Institutes of Health (NIH). NR 32 TC 33 Z9 33 U1 2 U2 27 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2013 VL 132 IS 3 BP 445 EP 453 DI 10.1542/peds.2013-0383 PG 9 WC Pediatrics SC Pediatrics GA 226ZX UT WOS:000325077800039 PM 23958770 ER PT J AU Kotte, A Joshi, G Fried, R Uchida, M Spencer, A Woodworth, KY Kenworthy, T Faraone, SV Biederman, J AF Kotte, Amelia Joshi, Gagan Fried, Ronna Uchida, Mai Spencer, Andrea Woodworth, K. Yvonne Kenworthy, Tara Faraone, Stephen V. Biederman, Joseph TI Autistic Traits in Children With and Without ADHD SO PEDIATRICS LA English DT Article DE ADD; ADHD; attention deficit disorder; attention-deficit/hyperactivity disorder; AT; autistic traits; autism traits; comorbidity; social disability ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HIGH-FUNCTIONING AUTISM; SPECTRUM DISORDERS; COGNITIVE FLEXIBILITY; MATERNAL INFECTION; ASPERGERS-SYNDROME; BIPOLAR DISORDER; MOTOR IMPAIRMENT; PERCEPTION DAMP AB OBJECTIVE: To assess the implications of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD) without a diagnosis of autism. METHODS: Participants were youth with (n = 242) and without (n = 227) ADHD and controls without ADHD in whom a diagnosis of autism was exclusionary. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. ATs were operationalized by using the withdrawn + social + thought problems T scores from the Child Behavior Checklist. RESULTS: A positive AT profile was significantly overrepresented among ADHD children versus controls (18% vs 0.87%; P < .001). ADHD children with the AT profile were significantly more impaired than control subjects in psychopathology, interpersonal, school, family, and cognitive domains. CONCLUSIONS: A substantial minority of ADHD children manifests ATs, and those exhibiting ATs have greater severity of illness and dysfunction. C1 [Kotte, Amelia; Fried, Ronna; Uchida, Mai; Spencer, Andrea; Woodworth, K. Yvonne; Kenworthy, Tara; Biederman, Joseph] Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Kotte, Amelia; Fried, Ronna; Uchida, Mai; Spencer, Andrea; Woodworth, K. Yvonne; Kenworthy, Tara; Biederman, Joseph] Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Joshi, Gagan; Fried, Ronna; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Joshi, Gagan] Massachusetts Gen Hosp, Alan & Lorraine Bressler Ctr, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Clin Program Pediat Psychopharmacol & Adult ADHD, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Kotte, Amelia/0000-0002-0198-7914; Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Mental Health [MH-41314, HD036317, MH050657]; Pediatric Psychopharmacology Research Council Fund; National Institutes of Health (NIH) FX The data acquisition from which this analysis was derived was funded by National Institute of Mental Health grants MH-41314, HD036317, and MH050657 to Dr Biederman. The manuscript and analysis of the data were indirectly supported by the Pediatric Psychopharmacology Research Council Fund. Funded by the National Institutes of Health (NIH). NR 58 TC 18 Z9 18 U1 2 U2 33 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2013 VL 132 IS 3 BP E612 EP E622 DI 10.1542/peds.2012-3947 PG 11 WC Pediatrics SC Pediatrics GA 226ZX UT WOS:000325077800006 PM 23979086 ER PT J AU Beaudoin, M Goyette, P Boucher, G Lo, KS Rivas, MA Stevens, C Alikashani, A Ladouceur, M Ellinghaus, D Torkvist, L Goel, G Lagace, C Annese, V Bitton, A Begun, J Brant, SR Bresso, F Cho, JH Duerr, RH Halfvarson, J McGovern, DPB Radford-Smith, G Schreiber, S Schumm, PL Sharma, Y Silverberg, MS Weersma, RK D'Amato, M Vermeire, S Franke, A Lettre, G Xavier, RJ Daly, MJ Rioux, JD AF Beaudoin, Melissa Goyette, Philippe Boucher, Gabrielle Lo, Ken Sin Rivas, Manuel A. Stevens, Christine Alikashani, Azadeh Ladouceur, Martin Ellinghaus, David Torkvist, Leif Goel, Gautam Lagace, Caroline Annese, Vito Bitton, Alain Begun, Jakob Brant, Steve R. Bresso, Francesca Cho, Judy H. Duerr, Richard H. Halfvarson, Jonas McGovern, Dermot P. B. Radford-Smith, Graham Schreiber, Stefan Schumm, Philip L. Sharma, Yashoda Silverberg, Mark S. Weersma, Rinse K. D'Amato, Mauro Vermeire, Severine Franke, Andre Lettre, Guillaume Xavier, Ramnik J. Daly, Mark J. Rioux, John D. CA Quebec IBD Genetics Consortium NIDDK IBD Genetics Consortium Int IBD Genetics Consortium TI Deep Resequencing of GWAS Loci Identifies Rare Variants in CARD9, IL23R and RNF186 That Are Associated with Ulcerative Colitis SO PLOS GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; INTESTINAL EPITHELIAL-CELLS; NUCLEAR FACTOR 4-ALPHA; SUSCEPTIBILITY LOCI; UBIQUITIN LIGASES; GENETIC-VARIANTS; CROHNS-DISEASE; EXPRESSION; LIVER AB Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (similar to 14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. C1 [Beaudoin, Melissa; Goyette, Philippe; Boucher, Gabrielle; Lo, Ken Sin; Alikashani, Azadeh; Ladouceur, Martin; Lagace, Caroline; Lettre, Guillaume; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Rivas, Manuel A.; Stevens, Christine] Broad Inst, Ctr Study IBD CSIBD Genet, Cambridge, MA USA. [Ellinghaus, David; Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Torkvist, Leif] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Goel, Gautam; Begun, Jakob; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Goel, Gautam; Begun, Jakob; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Annese, Vito] Ist Ricovero & Cura Carattere Sci Casa Sollievo S, Gastroenterol Unit, San Giovanni Rotondo, Italy. [Annese, Vito] Azienda Osped Univ AOU Careggi, Unit Gastroenterol SOD2, Florence, Italy. [Bitton, Alain] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Div Gastroenterol, Montreal, PQ H3A 1A1, Canada. [Brant, Steve R.] Johns Hopkins Univ, Sch Med, Dept Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD 21205 USA. [Brant, Steve R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Bresso, Francesca] Karolinska Univ Hosp, Dept Med, Solna, Sweden. [Cho, Judy H.; Sharma, Yashoda] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Cho, Judy H.; Sharma, Yashoda] Yale Univ, Dept Genet, New Haven, CT USA. [Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Halfvarson, Jonas] Orebro Univ Hosp, Dept Internal Med, Div Gastroenterol, Orebro, Sweden. [Halfvarson, Jonas] Univ Orebro, Sch Hlth & Med Sci, Orebro, Sweden. [McGovern, Dermot P. B.] Cedars Sinai Med Ctr, Cedars Sinai F Widjaja Inflammatory Bowel & Immun, Los Angeles, CA 90048 USA. [McGovern, Dermot P. B.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Radford-Smith, Graham] Univ Queensland, Royal Brisbane & Womens Hosp, Queensland Inst Med Res, Brisbane, Qld, Australia. [Radford-Smith, Graham] Univ Queensland, Royal Brisbane & Womens Hosp, Dept Gastroenterol, Brisbane, Qld, Australia. [Radford-Smith, Graham] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Schreiber, Stefan; Franke, Andre] Univ Kiel, Dept Gen Internal Med, Kiel, Germany. [Schumm, Philip L.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada. [Weersma, Rinse K.] Univ Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands. [Weersma, Rinse K.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden. [Vermeire, Severine] Univ Hosp Gasthuisberg, Div Gastroenterol, B-3000 Louvain, Belgium. [Lettre, Guillaume; Rioux, John D.] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada. [Xavier, Ramnik J.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. [Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA USA. RP Beaudoin, M (reprint author), Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. EM john.david.rioux@umontreal.ca RI Whiteman, David/P-2728-2014; Ellinghaus, David/G-4467-2012; Franke, Andre/B-2151-2010; Silverberg, Mark/B-4183-2008; Schreiber, Stefan/B-6748-2008; Begun, Jakob/J-6793-2014; Prescott, Natalie/F-6490-2011; Rioux, John/A-9599-2015; Mathew, Christopher/G-3434-2015; Palmieri, Orazio/J-7697-2012; OI Laukens, Debby/0000-0002-1984-5850; Panes, Julian/0000-0002-4971-6902; Cottone, Mario/0000-0003-1523-7556; Potocnik, Uros/0000-0003-1624-9428; Wijmenga, Cisca/0000-0002-5635-1614; Barrett, Jeffrey/0000-0002-1152-370X; D'Amato, Mauro/0000-0003-2743-5197; Latiano, Anna/0000-0003-3719-2061; Lee, James/0000-0001-5711-9385; Gearry, Richard/0000-0002-2298-5141; Halfvarson, Jonas/0000-0003-0122-7234; Newman, William/0000-0002-6382-4678; Whiteman, David/0000-0003-2563-9559; Franke, Andre/0000-0003-1530-5811; Schreiber, Stefan/0000-0003-2254-7771; Begun, Jakob/0000-0001-5256-7672; Prescott, Natalie/0000-0002-5901-7371; Duerr, Richard/0000-0001-6586-3905; Rioux, John/0000-0001-7560-8326; Mathew, Christopher/0000-0003-4178-1838; Palmieri, Orazio/0000-0002-0019-7929; Vermeire, Severine/0000-0001-9942-3019 FU Swedish Society of Medicine; Ihre Foundation; Orebro University Hospital Research Foundation; Karolinska Institutet; Swedish National Program; Swedish Organization; Swedish Medical Research Council; Netherlands Organization for Scientific Research (NWO) [90.700.281]; National Genome Research Network (NGFN) of the BMBF; US National Institutes of Diabetes, Digestive and Kidney Diseases [DK062432, DK064869]; Crohn's and Colitis Foundation of Canada (CCFC); Canadian Institutes of Health Research [GPG-102170]; [DK062431]; [DK062422]; [DK062429]; [DK062420]; [DK062423]; [DK062413] FX Research in Sweden was supported by the Swedish Society of Medicine, Ihre Foundation, Orebro University Hospital Research Foundation, Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, and the Swedish Medical Research Council. RKW is supported by a clinical fellowship grant (90.700.281) from the Netherlands Organization for Scientific Research (NWO). Genotyping of the German samples was supported by the National Genome Research Network (NGFN) of the BMBF. The German platform received infrastructure support from the DFG Cluster of Excellence "Inflammation at Interfaces" and the PopGen biobank. The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (SRB), DK062422 & DK062429 (JHC), DK062420 (RHD), DK062423 (MS), DK062413 (DPBM) and DK062432 (JDR). JDR holds a Canada Research Chair and is funded by grants from the US National Institutes of Diabetes, Digestive and Kidney Diseases (DK064869; DK062432), the Crohn's and Colitis Foundation of Canada (CCFC), and the Canadian Institutes of Health Research (GPG-102170). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 54 Z9 55 U1 3 U2 24 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2013 VL 9 IS 9 AR e1003723 DI 10.1371/journal.pgen.1003723 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 226ZM UT WOS:000325076600010 PM 24068945 ER PT J AU Glover-Cutter, KM Lin, S Blackwell, K AF Glover-Cutter, Kira M. Lin, Stephanie Blackwell, Keith TI Integration of the Unfolded Protein and Oxidative Stress Responses through SKN-1/Nrf SO PLOS GENETICS LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; MICROSOMAL 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE; TRANSCRIPTION FACTOR NRF1; RNA PROCESSING FACTORS; CAENORHABDITIS-ELEGANS; C-ELEGANS; MESSENGER-RNA; CELL-SURVIVAL; ER STRESS; LIFE-SPAN AB The Unfolded Protein Response (UPR) maintains homeostasis in the endoplasmic reticulum (ER) and defends against ER stress, an underlying factor in various human diseases. During the UPR, numerous genes are activated that sustain and protect the ER. These responses are known to involve the canonical UPR transcription factors XBP1, ATF4, and ATF6. Here, we show in C. elegans that the conserved stress defense factor SKN-1/Nrf plays a central and essential role in the transcriptional UPR. While SKN-1/Nrf has a well-established function in protection against oxidative and xenobiotic stress, we find that it also mobilizes an overlapping but distinct response to ER stress. SKN-1/Nrf is regulated by the UPR, directly controls UPR signaling and transcription factor genes, binds to common downstream targets with XBP-1 and ATF-6, and is present at the ER. SKN-1/Nrf is also essential for resistance to ER stress, including reductive stress. Remarkably, SKN-1/Nrf-mediated responses to oxidative stress depend upon signaling from the ER. We conclude that SKN-1/Nrf plays a critical role in the UPR, but orchestrates a distinct oxidative stress response that is licensed by ER signaling. Regulatory integration through SKN-1/Nrf may coordinate ER and cytoplasmic homeostasis. C1 [Glover-Cutter, Kira M.; Lin, Stephanie; Blackwell, Keith] Joslin Diabet Ctr, Harvard Stem Cell Inst, Boston, MA 02215 USA. [Glover-Cutter, Kira M.; Lin, Stephanie; Blackwell, Keith] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Glover-Cutter, KM (reprint author), USDA, Agr Res Serv, Corvallis, OR USA. EM keith.blackwell@joslin.harvard.edu OI Glover-Cutter, Kira/0000-0002-7321-8604 FU NIH [GM062891, GM094398]; NIDDK [DK036836, T32]; NRSA [F32GM090405] FX This work was supported by NIH grants GM062891 and GM094398 to TKB, a DRC grant from the NIDDK (DK036836), and NIDDK T32 and NRSA (F32GM090405) awards to KGC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 90 TC 39 Z9 42 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2013 VL 9 IS 9 AR e1003701 DI 10.1371/journal.pgen.1003701 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 226ZM UT WOS:000325076600002 PM 24068940 ER PT J AU O'Seaghdha, CM Wu, HS Yang, Q Kapur, K Guessous, I Zuber, AM Kottgen, A Stoudmann, C Teumer, A Kutalik, Z Mangino, M Dehghan, A Zhang, WH Eiriksdottir, G Li, G Tanaka, T Portas, L Lopez, LM Hayward, C Lohman, K Matsuda, K Padmanabhan, S Firsov, D Sorice, R Ulivi, S Brockhaus, AC Kleber, ME Mahajan, A Ernst, FD Gudnason, V Launer, LJ Mace, A Boerwinckle, E Arking, DE Tanikawa, C Nakamura, Y Brown, MJ Gaspoz, JM Theler, JM Siscovick, DS Psaty, BM Bergmann, S Vollenweider, P Vitart, V Wright, AF Zemunik, T Boban, M Kolcic, I Navarro, P Brown, EM Estrada, K Ding, JZ Harris, TB Bandinelli, S Hernandez, D Singleton, AB Girotto, G Ruggiero, D d'Adamo, AP Robino, A Meitinger, T Meisinger, C Davies, G Starr, JM Chambers, JC Boehm, BO Winkelmann, BR Huang, J Murgia, F Wild, SH Campbell, H Morris, AP Franco, OH Hofman, A Uitterlinden, AG Rivadeneira, F Volker, U Hannemann, A Biffar, R Hoffmann, W Shin, SY Lescuyer, P Henry, H Schurmann, C Munroe, PB Gasparini, P Pirastu, N Ciullo, M Gieger, C Marz, W Lind, L Spector, TD Smith, AV Rudan, I Wilson, JF Polasek, O Deary, IJ Pirastu, M Ferrucci, L Liu, YM Kestenbaum, B Kooner, JS Witteman, JCM Nauck, M Kao, WHL Wallaschofski, H Bonny, O Fox, CS Bochud, M AF O'Seaghdha, Conall M. Wu, Hongsheng Yang, Qiong Kapur, Karen Guessous, Idris Zuber, Annie Mercier Koettgen, Anna Stoudmann, Candice Teumer, Alexander Kutalik, Zoltan Mangino, Massimo Dehghan, Abbas Zhang, Weihua Eiriksdottir, Gudny Li, Guo Tanaka, Toshiko Portas, Laura Lopez, Lorna M. Hayward, Caroline Lohman, Kurt Matsuda, Koichi Padmanabhan, Sandosh Firsov, Dmitri Sorice, Rossella Ulivi, Sheila Brockhaus, A. Catharina Kleber, Marcus E. Mahajan, Anubha Ernst, Florian D. Gudnason, Vilmundur Launer, Lenore J. Mace, Aurelien Boerwinckle, Eric Arking, Dan E. Tanikawa, Chizu Nakamura, Yusuke Brown, Morris J. Gaspoz, Jean-Michel Theler, Jean-Marc Siscovick, David S. Psaty, Bruce M. Bergmann, Sven Vollenweider, Peter Vitart, Veronique Wright, Alan F. Zemunik, Tatijana Boban, Mladen Kolcic, Ivana Navarro, Pau Brown, Edward M. Estrada, Karol Ding, Jingzhong Harris, Tamara B. Bandinelli, Stefania Hernandez, Dena Singleton, Andrew B. Girotto, Giorgia Ruggiero, Daniela d'Adamo, Adamo Pio Robino, Antonietta Meitinger, Thomas Meisinger, Christa Davies, Gail Starr, John M. Chambers, John C. Boehm, Bernhard O. Winkelmann, Bernhard R. Huang, Jie Murgia, Federico Wild, Sarah H. Campbell, Harry Morris, Andrew P. Franco, Oscar H. Hofman, Albert Uitterlinden, Andre G. Rivadeneira, Fernando Voelker, Uwe Hannemann, Anke Biffar, Reiner Hoffmann, Wolfgang Shin, So-Youn Lescuyer, Pierre Henry, Hughes Schurmann, Claudia Munroe, Patricia B. Gasparini, Paolo Pirastu, Nicola Ciullo, Marina Gieger, Christian Maerz, Winfried Lind, Lars Spector, Tim D. Smith, Albert V. Rudan, Igor Wilson, James F. Polasek, Ozren Deary, Ian J. Pirastu, Mario Ferrucci, Luigi Liu, Yongmei Kestenbaum, Bryan Kooner, Jaspal S. Witteman, Jacqueline C. M. Nauck, Matthias Kao, W. H. Linda Wallaschofski, Henri Bonny, Olivier Fox, Caroline S. Bochud, Murielle CA SUNLIGHT Consortium GEFOS Consortium TI Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations SO PLOS GENETICS LA English DT Article ID IMPRINTED PHLDA2 GENE; VITAMIN-D METABOLISM; PARATHYROID-HORMONE; PHOSPHATE HOMEOSTASIS; PLACENTAL EXPRESSION; UROGENITAL SYSTEM; RENAL-FUNCTION; MAMMARY-GLAND; BIRTH-WEIGHT; PLASMA AB Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in <= 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis. C1 [O'Seaghdha, Conall M.; Wu, Hongsheng; Yang, Qiong; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Seaghdha, Conall M.; Wu, Hongsheng; Yang, Qiong; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. [Wu, Hongsheng; Yang, Qiong] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Wu, Hongsheng] Univ Split, Sch Med, Dept Med Biol, Split, Croatia. [Kapur, Karen; Kutalik, Zoltan; Mace, Aurelien; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Guessous, Idris; Bochud, Murielle] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland. [Guessous, Idris; Theler, Jean-Marc] Univ Hosp Geneva, Dept Community Med & Primary Care & Emergency Med, Div Primary Care Med, Unit Populat Epidemiol, Geneva, Switzerland. [Guessous, Idris] ASF, Geriatr Unit, Florence, Italy. [Zuber, Annie Mercier; Stoudmann, Candice; Firsov, Dmitri; Bonny, Olivier] Univ Lausanne, Dept Pharmacol & Toxicol, Lausanne, Switzerland. [Koettgen, Anna] Freiburg Univ Hosp, Div Renal, Freiburg, Germany. [Koettgen, Anna; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Teumer, Alexander; Ernst, Florian D.; Voelker, Uwe; Schurmann, Claudia] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Kutalik, Zoltan; Mace, Aurelien; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland. [Mangino, Massimo; Spector, Tim D.] Kings Coll London, London, England. [Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Zhang, Weihua; Chambers, John C.; Kooner, Jaspal S.] Ealing Gen Hosp, Catheter Lab, Southall, Middx, England. [Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Eiriksdottir, Gudny; Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Li, Guo; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Tanaka, Toshiko] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Portas, Laura; Murgia, Federico; Pirastu, Mario] CNR Traversa La Crucca, Inst Populat Genet, Sassari, Italy. [Lopez, Lorna M.; Davies, Gail; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Hayward, Caroline; Vitart, Veronique; Wright, Alan F.; Navarro, Pau] Univ Edinburgh, MRC IGMM, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Lohman, Kurt] ClinPhenomics GmbH&Co KG, Cardiol Grp, Frankfurt, Germany. [Matsuda, Koichi; Tanikawa, Chizu; Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan. [Padmanabhan, Sandosh] Univ Glasgow, Div Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Sorice, Rossella; Ruggiero, Daniela; Ciullo, Marina] CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80125 Naples, Italy. [Ulivi, Sheila; Girotto, Giorgia; d'Adamo, Adamo Pio; Robino, Antonietta; Gasparini, Paolo; Pirastu, Nicola] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy. [Brockhaus, A. Catharina; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany. [Brockhaus, A. Catharina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Kleber, Marcus E.] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany. [Mahajan, Anubha; Morris, Andrew P.] Wellcome Trust Ctr Human Genet, Oxford, England. [Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Reykjavik, Iceland. [Launer, Lenore J.; Harris, Tamara B.; Ferrucci, Luigi] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Boerwinckle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Brown, Morris J.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Gaspoz, Jean-Michel] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Vollenweider, Peter] Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland. [Zemunik, Tatijana; Kolcic, Ivana; Polasek, Ozren] Univ Split, Fac Med, Split, Croatia. [Boban, Mladen] Univ Split, Fac Med, Dept Pharmacol, Split, Croatia. [Brown, Edward M.; Ding, Jingzhong] Univ Hosp Geneva, Div Lab Med, Geneva, Switzerland. [Estrada, Karol; Uitterlinden, Andre G.; Rivadeneira, Fernando] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Bandinelli, Stefania] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England. [Hernandez, Dena; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Meitinger, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany. [Meitinger, Thomas] Wentworth Inst Technol, Dept Comp Sci & Networking, Boston, MA USA. [Meisinger, Christa] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, London, England. [Boehm, Bernhard O.] Univ Ulm, Dept Internal Med 1, Med Ctr, D-89069 Ulm, Germany. [Boehm, Bernhard O.] Univ London Imperial Coll Sci Technol & Med, LKC Sch Med, Singapore, Singapore. [Boehm, Bernhard O.] Nanyang Technol Univ, Singapore 639798, Singapore. [Winkelmann, Bernhard R.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Huang, Jie] Univ Hosp Geneva, Dept Community Med & Primary Care & Emergency Med, Div Primary Care Med, Geneva, Switzerland. [Wild, Sarah H.; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Hannemann, Anke; Nauck, Matthias; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Biffar, Reiner] Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany. [Hoffmann, Wolfgang] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Shin, So-Youn] Wellcome Trust Sanger Inst, Hinxton, England. [Lescuyer, Pierre] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Henry, Hughes] Univ Lausanne Hosp, Clin Chem Lab, Lausanne, Switzerland. [Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Maerz, Winfried] Synlab Ctr Lab Diagnost, Heidelberg, Germany. [Lind, Lars] Univ Uppsala Hosp, Inst Med Sci, Uppsala, Sweden. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Kestenbaum, Bryan] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, Fac Med, London, England. [Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London, England. [Kao, W. H. Linda] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Bonny, Olivier] Univ Lausanne Hosp, Serv Nephrol, Lausanne, Switzerland. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP O'Seaghdha, CM (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov; Murielle.Bochud@chuv.ch RI Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Rudan, Igor/I-1467-2012; Colaus, PsyColaus/K-6607-2013; Gasparini, Paolo/B-6173-2014; d'Adamo, Adamo Pio/G-4064-2011; Meisinger, Christine/B-5358-2014; Singleton, Andrew/C-3010-2009; Yang, Qiong/G-5438-2014; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Smith, Albert/K-5150-2015; ruggiero, daniela/K-5638-2016; Schurmann, Claudia/L-1204-2016; Bochud, Murielle/A-3981-2010; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Padmanabhan, Sandosh/S-3963-2016; Boban, Mladen/E-2777-2017; Kolcic, Ivana/E-2713-2017; OI Rivadeneira, Fernando/0000-0001-9435-9441; Rudan, Igor/0000-0001-6993-6884; d'Adamo, Adamo Pio/0000-0001-9367-4909; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Pirastu, Nicola/0000-0002-5363-3886; Padmanabhan, Sandosh/0000-0003-3869-5808; Gieger, Christian/0000-0001-6986-9554; Meisinger, Christa/0000-0002-9026-6544; Girotto, Giorgia/0000-0003-4507-6589; Navarro, Pau/0000-0001-5576-8584; Smith, Albert/0000-0003-1942-5845; ruggiero, daniela/0000-0003-3898-7827; Schurmann, Claudia/0000-0003-4158-9192; Bochud, Murielle/0000-0002-5727-0218; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Kolcic, Ivana/0000-0001-7918-6052; Lescuyer, Pierre/0000-0001-6986-8738 FU MIUR [5571/DSPAR/2002]; (FIRB) D. M. [718/Ric/2005]; [3100AO-116323/1,310000-112552]; [LSHG-CT-2006- 018947]; [108-1080315- 0302]; [N01-HC-25195]; [N02-HL-6-4278]; [N01AG62101]; [N01AG62103]; [N01AG62106]; [1R01AG032098-01A1]; [HHSN268200782096C]; [ICS110.1/RF97.71]; [263 MD 9164]; [263 MD 821336]; [N01-AG-1-2100]; [HHSN268201100005C]; [HHSN268201100006C]; [HHSN268201100007C]; [HHSN268201100008C]; [HHSN268201100009C]; [HHSN268201100010C]; [HHSN268201100011C]; [HSN268201100012C]; [01ZZ 0403]; [HEALTH-F2-2008-201865-GEFOS]; [HEALTH-F4-2007-201413]; [QLG2-CT-2002-01254]; [R01HL087641]; [R01HL59367]; [R01HL086694]; [U01HG004402]; [HHSN268200625226C]; [O3598/2-1]; [UL1RR025005]; [N01-HC-85239]; [N01-HC-85079]; [N01-HC-85080]; [N01-HC-85081]; [N01-HC-85082]; [N01-HC-85083]; [N01-HC-85084]; [N01-HC-85085]; [N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01 - HC-75150]; [N01-HC-45133]; [HHSN268201200036C]; [HL080295]; [HL087652]; [HL105756]; [AG-023629]; [AG]; [SP/04/002. G0700704/84698]; [LSHG-CT-2006-018947]; [01ZZ9603]; [01ZZ0103]; [01ZZ0403]; [03IS2061A]; [03ZIK012]; [175.010.2005.011]; [911-03-012]; [014-93-015]; [RIDE2. 050-060-810]; [vici, 918-76-619]; [Vasoplus-037254]; [FIRB - RBIN064YAT]; [LSHM-CT-2004-503485]; [WT064890]; [-15928]; [AG-20098]; [AG-027058]; [UL1RR033176]; [UL1TR000124]; [DK063491]; [33CSCO- 122661]; [3200BO-111361/2]; [WT081682]; [G20234]; [091746/Z/10/Z]; [G9521010D]; [PG/02/128]; [SP/04/002]; [PP00P3-133648] FX All grant numbers for each human study and for the animal studies are listed in the Acknowledgement section of the Supplementary material. There is no specific funding for the GWAS meta-analysis itself. Grant numbers: N01-AG-1-2100. HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HSN268201100012C, R01HL087641, R01HL59367, R01HL086694, U01HG004402, HHSN268200625226C. KO3598/2-1. UL1RR025005. N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01 - HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756, AG-023629, AG-15928, AG-20098, AG-027058, UL1RR033176, UL1TR000124, DK063491. 33CSCO- 122661, 3200BO-111361/2, 3100AO-116323/1,310000-112552. LSHG-CT-2006- 018947. 108- 1080315-0302. LSHG-CT-2006-018947, 108-1080315- 0302. 108-1080315- 0302. N01-HC-25195. N02-HL-6-4278. N01AG62101, N01AG62103, N01AG62106. 1R01AG032098-01A1. HHSN268200782096C. ICS110.1/RF97.71. 263 MD 9164 and 263 MD 821336. SP/04/002. G0700704/84698. (MIUR) no. 5571/DSPAR/2002 and (FIRB) D. M. no. 718/Ric/2005. LSHG-CT-2006-018947. 01ZZ9603, 01ZZ0103, 01ZZ0403, 03IS2061A, 03ZIK012. 175.010.2005.011, 911-03-012. 014-93-015; RIDE2. 050-060-810. vici, 918-76-619. Vasoplus-037254. FIRB - RBIN064YAT. LSHM-CT-2004-503485. WT064890, WT081682. 01ZZ9603, 01ZZ0103, and 01ZZ 0403. 03IS2061A. 03ZIK012. HEALTH-F2-2008-201865-GEFOS. HEALTH-F4-2007-201413. QLG2-CT-2002-01254. G20234. 091746/Z/10/Z. G9521010D. PG/02/128. SP/04/002. SP/04/002. PP00P3-133648. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 23 Z9 23 U1 1 U2 41 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2013 VL 9 IS 9 AR e1003796 DI 10.1371/journal.pgen.1003796 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 226ZM UT WOS:000325076600054 PM 24068962 ER PT J AU Taylor, JB Stern, TA AF Taylor, John B. Stern, Theodore A. TI Conflicts Between Consultants and Consultees: Causes, Consequences, and Corrective Actions SO PSYCHOSOMATICS LA English DT Article ID PSYCHIATRIC-CONSULTATION; RECOMMENDATIONS; CONCORDANCE C1 [Taylor, John B.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Taylor, JB (reprint author), Massachusetts Hosp, Dept Psychiat, 15 Parkman St, Boston, MA 02114 USA. EM taylor.john@mgh.harvard.edu NR 17 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2013 VL 54 IS 5 BP 479 EP 483 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 225LX UT WOS:000324965500010 PM 23473450 ER PT J AU Cardoos, A Inamori, A Sanacora, G Fava, M Mischoulon, D AF Cardoos, Amber Inamori, Aya Sanacora, Gerard Fava, Maurizio Mischoulon, David TI Delayed Amnesic Syndrome after Riluzole Use in Major Depressive Disorder: A Case Report SO PSYCHOSOMATICS LA English DT Article ID OPEN-LABEL TRIAL; SERUM CONCENTRATIONS; METABOLISM; RECEPTORS; SYMPTOMS; DISEASE; NMDA; MICE; ALS C1 [Cardoos, Amber; Inamori, Aya; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Sanacora, Gerard] Yale Univ, Clin Neurosci Res Unit, Dept Psychiat, Sch Med, New Haven, CT USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org FU NIMH [R01 MH08055]; Connecticut Department of Mental Health and Addiction Services FX This study was supported by the NIMH through R01 MH08055 (Gerard Sanacora) and the Connecticut Department of Mental Health and Addiction Services (Gerard Sanacora). NR 20 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2013 VL 54 IS 5 BP 488 EP 492 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 225LX UT WOS:000324965500012 PM 23473447 ER PT J AU Tan, CS Fintelmann, F Joe, J Ganguli, S Wu, S AF Tan, Chieh Suai Fintelmann, Florian Joe, Jennifer Ganguli, Suvranu Wu, Steven TI Coronary-Subclavian Steal Syndrome in a Hemodialysis Patient, a Case Report and Review of Literature SO SEMINARS IN DIALYSIS LA English DT Article ID INTERNAL THORACIC ARTERY; EXTREMITY ARTERIOVENOUS-FISTULA; DIALYSIS PATIENTS; MAMMARY GRAFT; STENOSIS AB Dialysis vascular access associated coronary-subclavian steal or hypoperfusion syndrome is an uncommon but potentially life threatening condition. Awareness of this syndrome is important in the management of vascular access in hemodialysis patients. We report a case of dialysis vascular access associated coronary-subclavian steal syndrome and review the literature on its pathogenesis and therapeutic implications. C1 [Tan, Chieh Suai; Fintelmann, Florian; Ganguli, Suvranu; Wu, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vasc Imaging & Intervent Div, Boston, MA 02114 USA. [Joe, Jennifer; Wu, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Joe, Jennifer; Wu, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Tan, Chieh Suai; Fintelmann, Florian; Ganguli, Suvranu; Wu, Steven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wu, S (reprint author), Massachusetts Gen Hosp, Dept Med & Radiol, Hemodialysis Vasc Access Program, 55 Fruit St, Boston, MA 02114 USA. EM wu.steven@mgh.harvard.edu NR 24 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD SEP PY 2013 VL 26 IS 5 BP E42 EP E46 DI 10.1111/sdi.12077 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 224XH UT WOS:000324925000001 PM 23458240 ER PT J AU Gracz, AD Fuller, MK Wang, FC Li, LH Stelzner, M Dunn, JCY Martin, MG Magness, ST AF Gracz, Adam D. Fuller, Megan K. Wang, Fengchao Li, Linheng Stelzner, Matthias Dunn, James C. Y. Martin, Martin G. Magness, Scott T. TI Brief Report: CD24 and CD44 Mark Human Intestinal Epithelial Cell Populations with Characteristics of Active and Facultative Stem Cells SO STEM CELLS LA English DT Article DE Tissue-specific stem cells; Cell surface markers; Fluorescence-activated cell sorting; Flow cytometry; Cell culture ID EXPRESSION MARKS; IN-VITRO; LGR5; EXPANSION; ORGANOIDS; COLON AB Recent seminal studies have rapidly advanced the understanding of intestinal epithelial stem cell (IESC) biology in murine models. However, the lack of techniques suitable for isolation and subsequent downstream analysis of IESCs from human tissue has hindered the application of these findings toward the development of novel diagnostics and therapies with direct clinical relevance. This study demonstrates that the cluster of differentiation genes CD24 and CD44 are differentially expressed across LGR5 positive active stem cells as well as HOPX positive facultative stem cells. Fluorescence-activated cell sorting enables differential enrichment of LGR5 (CD24-/CD44+) and HOPX (CD24+/CD44+) cells for gene expression analysis and culture. These findings provide the fundamental methodology and basic cell surface signature necessary for isolating and studying intestinal stem cell populations in human physiology and disease. STEM Cells2013;31:2024-2030 C1 [Gracz, Adam D.; Magness, Scott T.] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. [Gracz, Adam D.; Magness, Scott T.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA. [Fuller, Megan K.] Univ N Carolina, Dept Surg, Chapel Hill, NC 27599 USA. [Magness, Scott T.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Wang, Fengchao; Li, Linheng] Stowers Inst Med Res, Kansas City, MO USA. [Fuller, Megan K.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Stelzner, Matthias; Dunn, James C. Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Martin, Martin G.] Univ Calif Los Angeles, Dept Pediat, Div Gastroenterol, Los Angeles, CA 90024 USA. RP Magness, ST (reprint author), Univ N Carolina, 111 Mason Farm Rd,CB 7032,MBRB Rm 4337, Chapel Hill, NC 27599 USA. EM magness@med.unc.edu FU NC TraCS Institute Pilot Grant Program [2KR271103, 2KR381202]; Center for Gastrointestinal Biology and Disease [5P30DK034987-27]; University Cancer Research Fund Innovation Award; NIH National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health FX We thank the UNC flow cytometry facility (P30CA06086) and the neuroscience confocal facility, which is cofunded by the National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Human Development (P30NS045892). Drs. Timothy Farrell and Wayne Overby, and Myra Jones, Karen Colton, and Lisa Prestia, for coordinating the collection of deidentified remnant jejunal tissue from gastric-bypass operations. The Duke Human Vaccine Institute flow cytometry core, and Dr. John Whitesides and Ian Cumming, for technical assistance. Drs. Tope Keku and Robert Sandler for unpublished data regarding mucosal biopsy weight. Drs. P. Kay Lund, Susan Henning (SJH), and Christopher Dekaney for useful discussions and critical review of the manuscript. This work was funded by the NC TraCS Institute Pilot Grant Program, 2KR271103 (Gracz/Fuller) and 2KR381202 (Gracz), the Center for Gastrointestinal Biology and Disease, 5P30DK034987-27 (Magness), and a University Cancer Research Fund Innovation Award (Magness). The NC TraCS Institute is supported by Grants UL1RR025747, KL2RR025746, and TLRR025745 from the NIH National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health. The National Institute of Diabetes and Digestive and Kidney Diseases/National Institute of Allergy and Infectious Disease Intestinal Stem Cell Consortium (U01DK085541-SJH; U01DK85507-LL/FW; U01DK85535-MGM/JCYD/MS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 19 TC 28 Z9 28 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 2013 VL 31 IS 9 BP 2024 EP 2030 DI 10.1002/stem.1391 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 229II UT WOS:000325255700027 PM 23553902 ER PT J AU Wong, EB Cohen, KA Bishai, WR AF Wong, Emily B. Cohen, Keira A. Bishai, William R. TI Rising to the challenge: new therapies for tuberculosis SO TRENDS IN MICROBIOLOGY LA English DT Review DE tuberculosis; bedaquiline; PA-824; delamanid; clofazimine; oxazolidinones ID DRUG-RESISTANT TUBERCULOSIS; EARLY BACTERICIDAL ACTIVITY; MYCOBACTERIAL ATP SYNTHASE; MULTIDRUG-RESISTANT; PULMONARY TUBERCULOSIS; MURINE MODEL; INTERFERON-GAMMA; ANTITUBERCULOSIS ACTIVITY; DIARYLQUINOLINE TMC207; MEROPENEM-CLAVULANATE AB The standard treatment for tuberculosis (TB) is lengthy, complex, and significantly toxic. Drug development for TB has stagnated for decades, but in recent years renewed commitment and coordinated research has generated a modest pipeline of new drugs that hold the potential to make treatment more effective, shorter, less complex, and less toxic in the near future. With a particular focus on bedaquiline (TMC207), the first anti-TB drug of a novel class to be approved by the US Food and Drug Administration (FDA) in 40 years, this review summarizes the recent evidence behind new developments in TB treatment. Novel drug classes, repurposed drugs, and host-directed therapies are reviewed. In parallel to these exciting developments in drug discovery, we propose that it is crucial to develop more rapid and comprehensive diagnostics that will allow the timely selection of the best regimen for individual patients. C1 [Wong, Emily B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Wong, Emily B.; Cohen, Keira A.; Bishai, William R.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Bishai, William R.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. RP Bishai, WR (reprint author), KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. EM wbishai@jhmi.edu FU National Institutes of Health [AI036973, AI03856, AI097138, A107387]; Howard Hughes Medical Institute (HHMI) FX The authors gratefully acknowledge the support of the National Institutes of Health (grants AI036973, AI03856, AI097138 to W.R.B., and A107387 to E.B.W) and the Howard Hughes Medical Institute (HHMI). NR 76 TC 42 Z9 42 U1 1 U2 41 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 2013 VL 21 IS 9 BP 493 EP 501 DI 10.1016/j.tim.2013.05.002 PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 225NK UT WOS:000324969400009 PM 23764389 ER PT J AU Onoe, T Kalscheuer, H Yamada, K Sykes, M AF Onoe, Takashi Kalscheuer, Hannes Yamada, Kazuhiko Sykes, Megan TI Xenograft tolerance and immune functions of human T cells developing in pig thymus xenografts in humanized mice SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of 12th International-Xenotransplantation-Association and Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients CY NOV 10-13, 2013 CL Osaka, JAPAN SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc C1 [Onoe, Takashi; Kalscheuer, Hannes; Yamada, Kazuhiko; Sykes, Megan] Harvard Univ, Sch Med, Dept Surg, Transplantat Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kalscheuer, Hannes; Sykes, Megan] Columbia Univ, Coll Phys & Surg, Columbia Ctr Translat Immunol, Dept Med Surg & Microbiol Immunol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2013 VL 20 IS 5 SI SI BP 341 EP 342 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 224YG UT WOS:000324928400082 ER PT J AU Tasaki, M Wamala, I Aseda, T Trabi, R Villani, V Sekijima, M Hanekamp, I Sachs, D Yamada, K AF Tasaki, Masayuki Wamala, Isaac Aseda, Tena Trabi, Radbeh Villani, Vincenzo Sekijima, Mitsuhiro Hanekamp, Isabel Sachs, David Yamada, Kazuhiko TI Intra-bone bone marrow transplantation achieves longer peripheral macrochimerism and prolongs xeno-kidney graft survival in a pig-to-baboon xeno-transplantation model SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of 12th International-Xenotransplantation-Association and Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients CY NOV 10-13, 2013 CL Osaka, JAPAN SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc C1 [Tasaki, Masayuki; Wamala, Isaac; Aseda, Tena; Trabi, Radbeh; Villani, Vincenzo; Sekijima, Mitsuhiro; Hanekamp, Isabel; Sachs, David; Yamada, Kazuhiko] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2013 VL 20 IS 5 SI SI BP 341 EP 341 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 224YG UT WOS:000324928400080 ER PT J AU Tena, A Leonard, D Tasaki, M Mallard, C Germana, S Farkash, E Mastroianni, M Sachs, D Hawley, R AF Tena, Aseda Leonard, David Tasaki, Masayuki Mallard, Christopher Germana, Sharon Farkash, Evan Mastroianni, Melissa Sachs, David Hawley, Robert TI Initial evidence for functional immune modulation in primate recipients of porcine skin grafts following conditioning with human CD47 transgeneic pig hematopoietic stem cells SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of 12th International-Xenotransplantation-Association and Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients CY NOV 10-13, 2013 CL Osaka, JAPAN SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc C1 [Tena, Aseda; Leonard, David; Tasaki, Masayuki; Mallard, Christopher; Germana, Sharon; Mastroianni, Melissa; Sachs, David; Hawley, Robert] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Farkash, Evan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2013 VL 20 IS 5 SI SI BP 341 EP 341 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 224YG UT WOS:000324928400081 ER PT J AU Shimizu, A Yamada, K Sachs, DH Colvin, RB AF Shimizu, Akira Yamada, Kazuhiko Sachs, David H. Colvin, Robert B. TI Pathologic characteristics of transplanted GalTKO pig kidney xenografts in baboons SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of 12th International-Xenotransplantation-Association and Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients CY NOV 10-13, 2013 CL Osaka, JAPAN SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc C1 [Shimizu, Akira; Yamada, Kazuhiko; Sachs, David H.] Nippon Med Sch, Dept Pathol, Tokyo 113, Japan. [Shimizu, Akira] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Shimizu, Akira; Colvin, Robert B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2013 VL 20 IS 5 SI SI BP 349 EP 350 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 224YG UT WOS:000324928400105 ER PT J AU Sachs, DH AF Sachs, David H. TI Bone marrow xenotransplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of 12th International-Xenotransplantation-Association and Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients CY NOV 10-13, 2013 CL Osaka, JAPAN SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc C1 [Sachs, David H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2013 VL 20 IS 5 SI SI BP 350 EP 350 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 224YG UT WOS:000324928400107 ER PT J AU Tena, A Kurtz, J Leonard, D Mallard, C Germana, S Mtango, N Verstegen, J Sachs, D Hawley, R AF Tena, Aseda Kurtz, Josef Leonard, David Mallard, Christopher Germana, Sharon Mtango, Namdori Verstegen, John Sachs, David Hawley, Robert TI Engraftment and peripheral persistence of human CD47 transgenic porcine progenitor cells in CHEF-NSG mice SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of 12th International-Xenotransplantation-Association and Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients CY NOV 10-13, 2013 CL Osaka, JAPAN SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc C1 [Tena, Aseda; Kurtz, Josef; Leonard, David; Mallard, Christopher; Germana, Sharon; Sachs, David; Hawley, Robert] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Kurtz, Josef] Univ Cambridge Emmanuel Coll, Dept Biol, Boston, MA USA. [Mtango, Namdori; Verstegen, John] Minitube Amer, Verona, WI USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2013 VL 20 IS 5 SI SI BP 363 EP 364 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 224YG UT WOS:000324928400144 ER PT J AU Villani, V Sekijima, M Tasaki, M Torabi, R Cormack, T Torabi, R Moran, S Wilkinson, R Fishman, J Sachs, D Yamada, K AF Villani, Vincenzo Sekijima, Mitsuhiro Tasaki, Masayuki Torabi, Radbeh Cormack, Taylor Torabi, Ramyar Moran, Shannon Wilkinson, Robert Fishman, Jay Sachs, David Yamada, Kazuhiko TI Porcine CMV infection is associated with early rejection of kidney grafts in a pig-to-baboon xenotransplantation model SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of 12th International-Xenotransplantation-Association and Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients CY NOV 10-13, 2013 CL Osaka, JAPAN SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc C1 [Villani, Vincenzo; Sekijima, Mitsuhiro; Tasaki, Masayuki; Torabi, Radbeh; Cormack, Taylor; Torabi, Ramyar; Moran, Shannon; Sachs, David; Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Wilkinson, Robert; Fishman, Jay] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2013 VL 20 IS 5 SI SI BP 366 EP 366 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 224YG UT WOS:000324928400152 ER PT J AU Clark, S Espinola, JA Rudders, SA Banerji, A Camargo, CA AF Clark, Sunday Espinola, Janice A. Rudders, Susan A. Banerji, Aleena Camargo, Carlos A., Jr. TI Favorable trends in the frequency of US emergency department visits for food allergy, 2001-2009 SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID REPEAT EPINEPHRINE TREATMENTS; ANAPHYLACTIC REACTIONS; UNITED-STATES; MULTICENTER; PREVALENCE; CHILDREN; PEANUT AB Several studies suggest an increase in both the prevalence of food allergy and in the frequency of emergency department (ED) visits for food-related allergic reactions, including anaphylaxis. This study evaluates time trends in the frequency of ED visits for food allergy, with a focus on possible differences by age. Data from two multicenter ED-based studies were used to identify the proportion of patients assigned to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes with actual food-related acute allergic reaction and the proportion of these patients with food-induced anaphylaxis. We multiplied these proportions against counts from nationally representative data (2001-2009) to estimate the number of U.S. ED visits for each ICD-9-CM code with likely food allergy. Over the 9-year study period, there were similar to 1,892,000 ED visits for food allergy. The number of ED visits for food allergy did not significantly change among children aged <18 years (77,000 visits in 2001 versus 92,000 visits in 2009; p = 0.85), but among adults aged >= 18 years, there was a decline (147,000 visits versus 97,000 visits; p = 0.046). Looking across all ED visits (any cause), the proportion of ED visits for food allergy was stable for children (0.29% versus 0.28%; p = 0.22) but decreased for adults (0.18% versus 0.09%; p = 0.01). The number of U.S. ED visits for food-related acute allergic reactions is significantly higher than prior reports. These results also suggest that the frequency of ED visits for food allergy was stable or decreased from 2001 to 2009, despite reports suggesting an ongoing rise in the prevalence of food allergy. C1 [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY 10065 USA. [Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rudders, Susan A.] Hasbro Childrens Hosp, Ctr Asthma & Allergy, Providence, RI USA. [Banerji, Aleena; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Clark, S (reprint author), Weill Cornell Med Coll, Dept Emergency Med, 525 East 68th St,Box 179, New York, NY 10065 USA. EM suc2010@med.cornell.edu FU Food Allergy Research and Education (FARE), New York, New York FX Funded by Food Allergy Research and Education (FARE), New York, New York NR 33 TC 7 Z9 7 U1 1 U2 17 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 2013 VL 34 IS 5 BP 439 EP 445 DI 10.2500/aap.2013.34.3679 PG 7 WC Allergy SC Allergy GA 221OY UT WOS:000324669400007 PM 23998241 ER PT J AU Li, G Bekris, LM Leong, L Steinbart, EJ Shofer, JB Crane, PK Larson, EB Peskind, ER Bird, TD Yu, CE AF Li, Ge Bekris, Lynn M. Leong, Lesley Steinbart, Ellen J. Shofer, Jane B. Crane, Paul K. Larson, Eric B. Peskind, Elaine R. Bird, Thomas D. Yu, Chang-En TI TOMM40 intron 6 poly-T length, age at onset, and neuropathology of AD in individuals with APOE epsilon 3/epsilon 3 SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Age at onset; Genetic; APOE; TOMM40; PSEN1 mutation; PSEN2 mutation; Neuropathology ID FAMILIAL ALZHEIMERS-DISEASE; GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E; PROTEIN-LEVELS; DIAGNOSIS; DEMENTIA; COHORT; LOCI; PRESENILIN-1; SENSITIVITY AB Background: This study investigates the association between TOMM40 poly-T length, age at onset, and neuropathology in individuals with Alzheimer's disease (AD) with the apolipoprotein E (APOE) epsilon 3/epsilon 3 allele. Methods: Thirty-two presenilin 1 (PSEN1) mutation carriers with AD, 27 presenilin 2 (PSEN2) mutation carriers with AD, 59 participants with late-onset AD (LOAD), and 168 autopsied subjects from a community-based cohort were genotyped for TOMM40 intron 6 poly-T (rs10524523) length using short tandem repeat assays. Results: Among AD individuals with PSEN2 mutations, the presence of a long poly-T was associated with an earlier age at onset, whereas there were no such associations for subjects with PSEN1 mutations or LOAD. In community-based participants, the presence of a long poly-T was associated with increased neuritic tangles and a greater likelihood of pathologically diagnosed AD. Conclusion: TOMM40 intron 6 poly-T length may explain some of the variation in age at onset in PSEN2 familial AD and may be associated with AD neuropathology in persons with APOE epsilon 3/epsilon 3. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Li, Ge; Shofer, Jane B.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bekris, Lynn M.; Crane, Paul K.; Larson, Eric B.; Yu, Chang-En] Univ Washington, Dept Med, Seattle, WA USA. [Bekris, Lynn M.; Leong, Lesley; Steinbart, Ellen J.; Bird, Thomas D.; Yu, Chang-En] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Steinbart, Ellen J.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Li, G (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM gli@u.washington.edu RI Crane, Paul/C-8623-2014 FU National Institute of Aging [AG033693, AG006781, AG05136, AG034214]; U.S. Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program FX This study was supported by grants AG033693, AG006781, AG05136, and AG034214 from the National Institute of Aging and by the U.S. Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program. The study sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. NR 43 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD SEP PY 2013 VL 9 IS 5 BP 554 EP 561 DI 10.1016/j.jalz.2012.06.009 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 222IN UT WOS:000324724500009 PM 23183136 ER PT J AU Geda, YE Schneider, LS Gitlin, LN Miller, DS Smith, GS Bell, J Evans, J Lee, M Porsteinsson, A Lanctot, KL Rosenberg, PB Sultzer, DL Francis, PT Brodaty, H Padala, PP Onyike, CU Ortiz, LA Ancoli-Israel, S Bliwise, DL Martin, JL Vitiello, MV Yaffe, K Zee, PC Herrmann, N Sweet, RA Ballard, C Khin, NA Alfaro, C Murray, PS Schultz, S Lyketsos, CG AF Geda, Yonas E. Schneider, Lon S. Gitlin, Laura N. Miller, David S. Smith, Gwenn S. Bell, Joanne Evans, Jovier Lee, Michael Porsteinsson, Anton Lanctot, Krista L. Rosenberg, Paul B. Sultzer, David L. Francis, Paul T. Brodaty, Henry Padala, Prasad P. Onyike, Chiadikaobi U. Ortiz, Luis Agueera Ancoli-Israel, Sonia Bliwise, Donald L. Martin, Jennifer L. Vitiello, Michael V. Yaffe, Kristine Zee, Phyllis C. Herrmann, Nathan Sweet, Robert A. Ballard, Clive Khin, Ni A. Alfaro, Cara Murray, Patrick S. Schultz, Susan Lyketsos, Constantine G. CA Neuropsychiat Syndromes TI Neuropsychiatric symptoms in Alzheimer's disease: Past progress and anticipation of the future SO ALZHEIMERS & DEMENTIA LA English DT Article DE Neuropsychiatric symptoms; Behavioral and psychological symptoms of dementia; Agitation/aggression; Sleep disorders; Depression; Apathy; Psychosis; Delusions; Hallucinations; Dementia; Alzheimer's disease; Mild cognitive impairment; Mild behavioral impairment ID MILD COGNITIVE IMPAIRMENT; VASCULAR DEPRESSION HYPOTHESIS; PITTSBURGH COMPOUND-B; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; BEHAVIORAL SYMPTOMS; NATIONAL INSTITUTE; RANDOMIZED-TRIAL; RATING-SCALE; DOUBLE-BLIND AB Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS-PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome-specific synthetic reviews and recommendations prepared by NPS-PIA workgroups on depression, apathy, sleep, agitation, and psychosis. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Geda, Yonas E.] Mayo Clin, Coll Med, Dept Psychiat, Scottsdale, AZ USA. [Geda, Yonas E.] Mayo Clin, Coll Med, Dept Neurol, Scottsdale, AZ USA. [Schneider, Lon S.] Univ So Calif, Los Angeles, CA USA. [Gitlin, Laura N.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Miller, David S.] Bracket, Wayne, PA USA. [Smith, Gwenn S.; Rosenberg, Paul B.; Onyike, Chiadikaobi U.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21218 USA. [Evans, Jovier] NIMH, Geriatr Res Branch, Geriatr Translat Neurosci & MultiModal Interv Pro, Geriatr Pharmacol Intervent, Bethesda, MD 20892 USA. [Lee, Michael] Univ Minnesota, Inst Translat Neurosci, Dept Neurosci, Minneapolis, MN USA. [Lee, Michael] Univ Minnesota, Inst Translat Neurosci, Ctr Neurodegenerat Dis, Minneapolis, MN USA. [Porsteinsson, Anton] Univ Rochester, Sch Med & Dent Rochester, Dept Psychiat, Rochester, NY USA. [Lanctot, Krista L.] Sunnybrook Res Inst, Brain Sci Program, Toronto, ON, Canada. [Lanctot, Krista L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Lanctot, Krista L.] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. [Lanctot, Krista L.] Univ Toronto, Dept Toxicol, Toronto, ON, Canada. [Sultzer, David L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Sultzer, David L.] VA Greater Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. [Francis, Paul T.] Kings Coll London, Wolfson Ctr Age Related Dis, London, England. [Brodaty, Henry] Univ New S Wales, Dementia Collaborat Res Ctr, Sydney, NSW, Australia. [Padala, Prasad P.] Cent Arkansas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr, Little Rock, AR USA. [Padala, Prasad P.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. [Ortiz, Luis Agueera] C1BERSAM, Madrid, Spain. [Ortiz, Luis Agueera] Univ Hosp Doce Octubre, Madrid, Spain. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Bliwise, Donald L.] Emory Univ, Sch Med, Wesley Woods Hlth Ctr, Dept Neurol, Atlanta, GA USA. [Martin, Jennifer L.] Univ Calif Los Angeles, Educ & Clin Ctr, VA Greater Angeles Healthcare Geriatr Res, Los Angeles, CA USA. [Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Vitiello, Michael V.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Zee, Phyllis C.] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.; Murray, Patrick S.] VA Pittsburgh Healthcare Syst, VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Pittsburgh, PA USA. [Ballard, Clive] Kings Coll London, Wolfson Ctr Age Related Dis, Biomed Res Unit, Inst Psychiat & Alzheimers Soc, London WC2R 2LS, England. [Khin, Ni A.; Alfaro, Cara] US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 1 OND, Div Psychiat Prod, Silver Spring, MD USA. [Schultz, Susan] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA USA. RP Lyketsos, CG (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21218 USA. RI Lee, Michael/D-9491-2013; Francis, Paul/A-9199-2008; OI Lee, Michael/0000-0001-5865-9682; Murray, Patrick/0000-0002-6525-2888; Vitiello, Michael/0000-0002-9776-0473; Lanctot, Krista L./0000-0001-7024-6637 FU NIMH [K01-MH68351, R24-MH074779, R01-MH079814, RC1-MH090770-01]; NIA [U01-AG006786]; National Center for Research Resources [RR024150]; Robert Wood Johnson Foundation; European Union Regional Development Fund [FNUSA-ICRC: CZ.1.05/1.1.00/02.0123]; Baxter; Elan Pharmaceuticals; Johnson Johnson; Eli Lilly; Myriad; Novartis; Pfizer; Abbott Laboratories; AC Immune; Allergan; Allon; Alzheimer Drug Discovery Foundation; AstraZeneca; Bristol-Myers Squibb; Elan; Exonhit; Forest; GlaxoSmithKline; Ipsen Pharmaceuticals; Lundbeck; Medavante; Medivation; Merck; Merz; Roche; Sanofi-Aventis; Schering-Plough; Schwabe; Toyama; Transition Therapeutics; Alzheimer's Association [IIRG-07-28686]; Johns Hopkins Alzheimer's Disease Research Center [P50-AG005146]; NIMH, MA; Associated Jewish Federation of Baltimore; Weinberg Foundation; Eisai; Lilly; Ortho-McNeil; Bristol-Myers; National Football League; Functional Neuromodulation Inc. FX The authors thank Dr. Michelle M. Mielke for her helpful comments and feedback on early drafts of this manuscript. Dr. Geda was supported by NIMH grant K01-MH68351, NIA grant U01-AG006786 (the Mayo Clinic Study of Aging), National Center for Research Resources grant RR024150 (Mayo Clinic CTSA [Career Transition Award]), the Robert Wood Johnson Foundation (Harold Amos Scholar), and the European Union Regional Development Fund (Project FNUSA-ICRC: CZ.1.05/1.1.00/02.0123). Dr. Schneider reports being an editor on the Cochrane Collaboration Dementia and Cognitive Improvement Group, which oversees systematic reviews of drugs for cognitive impairment and dementia. He received a grant from the Alzheimer's Association for a registry for dementia and cognitive impairment trials; he is also in receipt of grant or research support from Baxter, Elan Pharmaceuticals, Johnson & Johnson, Eli Lilly, Myriad, Novartis, and Pfizer. He has served as a consultant for or received consulting fees from Abbott Laboratories, AC Immune, Allergan, Allon, the Alzheimer Drug Discovery Foundation, AstraZeneca, Bristol-Myers Squibb, Elan, Eli Lilly, Exonhit, Forest, GlaxoSmithKline, Ipsen Pharmaceuticals, Johnson & Johnson, Lundbeck, Myriad, Medavante, Medivation, Merck, Merz, Novartis, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, Schwabe, Toyama, and Transition Therapeutics. Dr. Gitlin was supported by NIMH grants R24-MH074779, R01-MH079814, and RC1-MH090770-01 and Alzheimer's Association grant IIRG-07-28686 and served on the Phillips Life Line Falls Advisory Board. Dr. Miller is a full-time employee of Bracket. Dr. Lyketsos was supported by the Johns Hopkins Alzheimer's Disease Research Center (P50-AG005146). He has received grant support (research or CME) from NIMH, MA, the Associated Jewish Federation of Baltimore, the Weinberg Foundation, Forest, GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis, the National Football League, Elan, and Functional Neuromodulation Inc. He has served as consultant/advisor for AstraZeneca, GlaxoSmithKline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, the NFL Players Association, the NFL Benefits Office, Avanir, and Zinfandel. He has also received honorarium or travel support from Pfizer, Forest, GlaxoSmithKline, and Health Monitor. NR 68 TC 75 Z9 76 U1 8 U2 43 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD SEP PY 2013 VL 9 IS 5 BP 602 EP 608 DI 10.1016/j.jalz.2012.12.001 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 222IN UT WOS:000324724500015 PM 23562430 ER PT J AU Watson, GS Cholerton, BA Gross, RG Weintraub, D Zabetian, CP Trojanowski, JQ Montine, TJ Siderowf, A Leverenz, JB AF Watson, G. Stennis Cholerton, Brenna A. Gross, Rachel G. Weintraub, Daniel Zabetian, Cyrus P. Trojanowski, John Q. Montine, Thomas J. Siderowf, Andrew Leverenz, James B. TI Neuropsychologic assessment in collaborative Parkinson's disease research: A proposal from the National Institute of Neurological Disorders and Stroke Morris K. Udall Centers of Excellence for Parkinson's Disease Research at the University of Pennsylvania and the University of Washington SO ALZHEIMERS & DEMENTIA LA English DT Article ID MONTREAL COGNITIVE ASSESSMENT; DEMENTIA; MOCA; IMPAIRMENT; SYMPTOMS; VALIDITY; COHORT; MMSE; MCI AB Cognitive impairment (CI) and behavioral disturbances can be the earliest symptoms of Parkinson's disease (PD), ultimately afflict the vast majority of PD patients, and increase caregiver burden. Our two Morris K. Udall Centers of Excellence for Parkinson's Disease Research were supported by the National Institute of Neurological Disorders and Stroke (NINDS) in an effort to recommend a comprehensive yet practical approach to cognitive and behavioral assessment to further collaborative research. We recommend a stepwise approach with two levels of standardized evaluation to establish a common battery, as well as an alternative testing recommendation for severely impaired subjects, and review supplemental tests that may be useful in specific research settings. Our flexible approach may be applied to studies with varying emphasis on cognition and behavior, does not place undue burden on participants or resources, and has a high degree of compatibility with existing test batteries to promote collaboration. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Watson, G. Stennis; Cholerton, Brenna A.; Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Gross, Rachel G.; Weintraub, Daniel; Siderowf, Andrew] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Gross, Rachel G.; Weintraub, Daniel; Siderowf, Andrew] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Zabetian, Cyrus P.] Vet AffairsPuget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Trojanowski, John Q.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Trojanowski, John Q.] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. [Trojanowski, John Q.] Univ Penn, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Leverenz, JB (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM leverenz@uw.edu FU NINDS [NS062684, NS053488]; Nancy and Buster Alvord Endowment FX This study was funded by NINDS (NS062684, NS053488) and the Nancy and Buster Alvord Endowment. The authors thank Dr Kathy Montine for editorial assistance. NR 27 TC 4 Z9 4 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD SEP PY 2013 VL 9 IS 5 BP 609 EP 614 DI 10.1016/j.jalz.2012.07.006 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 222IN UT WOS:000324724500016 PM 23164549 ER PT J AU Lysack, C Leach, C Russo, T Paulson, D Lichtenberg, PA AF Lysack, Cathy Leach, Carrie Russo, Theresa Paulson, Daniel Lichtenberg, Peter A. TI DVD Training for Depression Identification and Treatment in Older Adults: A Two-Group, Randomized, Wait-List Control Study SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE depression; education, continuing; geriatric assessment; staff development; teaching ID LATE-LIFE DEPRESSION; HOME-CARE; OCCUPATIONAL-THERAPY; TREATING DEPRESSION; CONTROLLED-TRIAL; HEALTH-STATUS; INTERVENTION; RECOGNITION; SCALE; MOOD AB OBJECTIVE. To test the effectiveness of an educational intervention aimed at improving mental health. knowledge and skills in occupational therapists working with older rehabilitation patients. METHOD. The DVD-format educational intervention was evaluated using a two-group randomized wait-list control design. Occupational therapists (n = 75) completed a 32-item knowledge questionnaire at three time points. Patient charts were reviewed (n = 960) at 3 months before and 3 and 6 months after DVD training to evaluate clinical practice change. RESULTS. A two-way analysis of variance showed knowledge scores increased significantly for both groups after DVD training. A significant Group x Time interaction and significant main effects for time and group were found. Chart review data also showed significant increases in desired clinical behaviors in both groups after training. The greatest single item of clinical practice change was use of a standardized depression screen. CONCLUSION. DVD-based training can significantly improve mental health practice. C1 [Lysack, Cathy; Leach, Carrie; Lichtenberg, Peter A.] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. [Russo, Theresa] Alzheimers Assoc Greater Michigan Chapter, Southfield, MI USA. [Paulson, Daniel] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. [Paulson, Daniel] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Lichtenberg, Peter A.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48202 USA. RP Lysack, C (reprint author), Wayne State Univ, Inst Gerontol, Room 231,Knapp Bldg,87 East Ferry St, Detroit, MI 48202 USA. EM c.lysack@wayne.edu NR 30 TC 1 Z9 1 U1 1 U2 7 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD SEP-OCT PY 2013 VL 67 IS 5 BP 584 EP 593 DI 10.5014/ajot.2013.008060 PG 10 WC Rehabilitation SC Rehabilitation GA 220EQ UT WOS:000324565400012 PM 23968797 ER PT J AU Mustafa, M Zarrough, A Bolstad, AI Lygre, H Mustafa, K Hasturk, H Serhan, C Kantarci, A Van Dyke, TE AF Mustafa, Manal Zarrough, Ahmed Bolstad, Anne Isine Lygre, Henning Mustafa, Kamal Hasturk, Hatice Serhan, Charles Kantarci, Alpdogan Van Dyke, Thomas E. TI Resolvin D1 protects periodontal ligament SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE regeneration; inflammation; resolution ID HUMAN GINGIVAL FIBROBLASTS; FACTOR-KAPPA-B; CONNECTIVE-TISSUE; LIPID MEDIATORS; GROWTH-FACTOR; CYCLOOXYGENASE-2 INHIBITOR; ACUTE-INFLAMMATION; HUMAN-NEUTROPHILS; IN-VITRO; CELLS AB Resolution agonists are endogenous mediators that drive inflammation to homeostasis. We earlier demonstrated in vivo activity of resolvins and lipoxins on regenerative periodontal wound healing. The goal of this study was to determine the impact of resolvin D1 (RvD1) on the function of human periodontal ligament (PDL) fibroblasts, which are critical for wound healing during regeneration of the soft and hard tissues around teeth. Primary cells were cultured from biopsies obtained from three individuals free of periodontal diseases. Peripheral blood mononuclear cells were isolated by density gradient centrifugation from whole blood of healthy volunteers. PGE(2), leukotriene B-4 (LTB4), and lipoxin A(4) (LXA(4)) in culture supernatants were measured by ELISA. The direct impact of RvD1 on PDL fibroblast proliferation was measured and wound closure was analyzed in vitro using a fibroblast culture "scratch assay." PDL fibroblast function in response to RvD1 was further characterized by basic FGF production by ELISA. IL-1 beta and TNF-alpha enhanced the production of PGE(2). Treatment of PDL cells and monocytes with 0.1-10 ng/ml RvD1 (0.27-27 M) reduced cytokine induced production of PGE(2) and upregulated LXA(4) production by both PDL cells and monocytes. RvD1 significantly enhanced PDL fibroblast proliferation and wound closure as well as basic FGF release. The results demonstrate that anti-inflammatory and proresolution actions of RvD1 with upregulation of arachidonic acid-derived endogenous resolution pathways (LXA(4)) and suggest resolution pathway synergy establishing a novel mechanism for the proresolution activity of the omega-3 docosahexaenoic acid-derived resolution agonist RvD1. C1 [Mustafa, Manal; Mustafa, Kamal] Univ Bergen, Ctr Clin Dent Res, Dept Clin Dentistry, Bergen, Norway. [Mustafa, Manal; Zarrough, Ahmed; Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. [Bolstad, Anne Isine] Univ Bergen, Dept Clin Dentistry Periodont, Bergen, Norway. [Lygre, Henning] Univ Bergen, Pharmacol Sect, Inst Med, Bergen, Norway. [Serhan, Charles] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Serhan, Charles] Harvard Univ, Sch Med, Boston, MA USA. RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org FU National Institute of Dental and Craniofacial Research [1R01-DE-019938]; Research Council of Norway; Meltzer Foundation; University of Bergen; Helse Vest; Friforsk Program Project [710020] FX This work was supported by National Institute of Dental and Craniofacial Research Grant 1R01-DE-019938 (to T. Van Dyke and C. Serhan) and a grant from the Research Council of Norway, Meltzer Foundation, University of Bergen, Helse Vest, and Friforsk Program Project No. 710020. NR 63 TC 13 Z9 13 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 2013 VL 305 IS 6 BP C673 EP C679 DI 10.1152/ajpcell.00242.2012 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 220OZ UT WOS:000324595700010 PM 23864609 ER PT J AU Stengel, A Goebel-Stengel, M Wang, L Hu, E Karasawa, H Pisegna, JR Tache, Y AF Stengel, Andreas Goebel-Stengel, Miriam Wang, Lixin Hu, Eugenia Karasawa, Hiroshi Pisegna, Joseph R. Tache, Yvette TI High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE diet-induced obesity; food intake; high-protein diet; gut hormones ID CONDITIONED TASTE-AVERSION; WEIGHT-LOSS DIETS; FOOD-INTAKE; BODY-WEIGHT; INDUCED THERMOGENESIS; RESPIRATION CHAMBER; CEREBROSPINAL-FLUID; ENERGY RESTRICTION; METABOLIC SYNDROME; INSULIN-SECRETION AB Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. C1 [Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.; Tache, Yvette] Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress, CURE,Digest Dis Res Ctr,Digest Dis Div, Los Angeles, CA 90024 USA. [Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.; Tache, Yvette] VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. [Stengel, Andreas] Charite Ctr Internal Med & Dermatol, Obes Ctr Berlin, D-13353 Berlin, Germany. [Stengel, Andreas] Charite, D-13353 Berlin, Germany. [Goebel-Stengel, Miriam] Inst Neurogastroenterol & Motility, Dept Internal Med, Berlin, Germany. [Goebel-Stengel, Miriam] Martin Luther Hosp, Berlin, Germany. RP Tache, Y (reprint author), CURE, VA GLA Healthcare Syst, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu RI Biguzzi, Felipe/E-4724-2015 FU VA Merit award; National Institute of Health center grant [DK-41301]; VA Career Scientist Award; [5 RC1 DK-086150-02] FX This article was supported by VA Merit award (to Y. Tache and J. R. Pisegna), National Institute of Health center grant DK-41301 (Animal Core, to Y. Tache), VA Career Scientist Award (to Y. Tache) and 5 RC1 DK-086150-02 (S. B., C.P.). NR 62 TC 8 Z9 8 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2013 VL 305 IS 6 BP R582 EP R591 DI 10.1152/ajpregu.00598.2012 PG 10 WC Physiology SC Physiology GA 222TA UT WOS:000324753200003 PM 23883680 ER PT J AU Parekh, A Chen, MH D'Amico, AV Dosoretz, DE Ross, R Salenius, S Graham, PL Beckman, JA Beard, CJ Choueiri, TK Ennis, RD Hoffman, KE Hu, JC Ma, J Martin, NE Nguyen, PL AF Parekh, Arti Chen, Ming-Hui D'Amico, Anthony V. Dosoretz, Daniel E. Ross, Rudi Salenius, Sharon Graham, Powell L. Beckman, Joshua A. Beard, Clair J. Choueiri, Toni K. Ennis, Ronald D. Hoffman, Karen E. Hu, Jim C. Ma, Jing Martin, Neil E. Nguyen, Paul L. TI Identification of comorbidities that place men at highest risk of death from androgen deprivation therapy before brachytherapy for prostate cancer SO BRACHYTHERAPY LA English DT Article DE Androgen deprivation therapy; Prostate cancer; Comorbidity; Diabetes; Cardiac death ID SUPPRESSION; RADIOTHERAPY; RADIATION; ASSOCIATION; MORTALITY; DISEASE; TRIAL AB PURPOSE: To determine which specific comorbidities predispose men to excess mortality by androgen deprivation therapy (ADT) given before and during brachytherapy for prostate cancer. METHODS AND MATERIALS: We analyzed 5972 men with Tlc-T3b prostate cancer treated with brachytherapy-based radiation with or without neoadjuvant ADT. Cox multivariable analysis with propensity scoring was used to determine if ADT was associated with increased all-cause mortality (ACM) in men divided into groups stratified by cardiac comorbidities. Tests for interaction between risk group and outcome were performed. RESULTS: ADT was associated with increased ACM in men with a history of myocardial infarction or congestive heart failure, regardless of whether they underwent revascularization (adjusted hazard ratio [AHR], 2.1 [95% confidence interval {CI}, 1.02-4.17; p = 0.04]) or not (ABER, 1.8 [95% CI, 1.05-3.20; p = 0.03]), but this effect was not seen in men with less severe comorbidity. However, among men with diabetes, there was a significant interaction with risk group (p = 0.01) such that ADT was associated with excess mortality in men with low-risk disease (AHR = 2.21 [1.04-4.68]; p = 0.04) but not in men with intermediate or high-risk disease (AHR, 0.64 [0.33-1.22]; p = 0.17). CONCLUSIONS: ADT was associated with excess ACM in all patients with a history of congestive heart failure or myocardial infarction, regardless of whether they were revascularized, and in diabetics with low-risk disease. ADT for gland downsizing before brachytherapy should be avoided in these men. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Parekh, Arti; D'Amico, Anthony V.; Graham, Powell L.; Beard, Clair J.; Martin, Neil E.; Nguyen, Paul L.] Harvard Univ, Dana Farber Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Dosoretz, Daniel E.; Ross, Rudi; Salenius, Sharon] 21st Century Oncol, Ft Myers, FL USA. [Beckman, Joshua A.] Harvard Univ, Dana Farber Brigham & Womens Hosp, Sch Med, Dept Cardiol, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Dana Farber Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Ennis, Ronald D.] Albert Einstein Coll Med, Continuum Canc Ctr NY, St Lukes Roosevelt & Beth Israel Hosp, Dept Radiat Oncol, New York, NY USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Hu, Jim C.] Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA 90024 USA. [Ma, Jing] Harvard Univ, Dana Farber Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Dana Farber Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Beckman, Joshua/0000-0001-8332-8439 FU anonymous family foundation; Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School; David and Cynthia Chapin; JCRT Foundation; Fitz's Cancer Warriors; Heritage Medical Research Institute - Prostate Cancer Foundation Young Investigator Award FX This work was supported by an anonymous family foundation, the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School, David and Cynthia Chapin, a JCRT Foundation Grant, Fitz's Cancer Warriors, and Heritage Medical Research Institute - Prostate Cancer Foundation Young Investigator Award. NR 18 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD SEP-OCT PY 2013 VL 12 IS 5 BP 415 EP 421 DI 10.1016/j.brachy.2013.02.005 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 221KI UT WOS:000324657400007 PM 23651926 ER PT J AU Kansal, KJ Dominici, LS Tolaney, SM Isakoff, SJ Smith, BL Jiang, W Brock, JE Winer, EP Krop, IE Golshan, M AF Kansal, Kari Joanne Dominici, Laura Stewart Tolaney, Sara M. Isakoff, Steven J. Smith, Barbara L. Jiang, Wei Brock, Jane E. Winer, Eric P. Krop, Ian E. Golshan, Mehra TI Neoadjuvant bevacizumab: surgical complications of mastectomy with and without reconstruction SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; HER2-negative breast cancer; Neoadjuvant chemotherapy; Bevacizumab; Mastectomy; Postoperative complications ID METASTATIC BREAST-CANCER; PREOPERATIVE CHEMOTHERAPY; ADJUVANT BREAST; SURGERY; B-18 AB Neoadjuvant therapy (NAC) is commonly used in operable breast cancer. Previous studies have suggested a high rate of postoperative complications after NAC. We prospectively evaluated the surgical complications in a cohort of patients who underwent mastectomy following neoadjuvant adriamycin/cytoxan/taxol (AC/T) plus bevacizumab (bev) and compared the rate of complications to a matched cohort of neoadjuvant AC/T without bev. One hundred patients with HER2-negative breast cancer enrolled in a single-arm trial of neoadjuvant AC/T plus bev (cohort 1), 60 of these patients underwent mastectomy and were matched with 59 patients who received standard neoadjuvant AC/T (cohort 2) over a similar time period in the same healthcare system. All patients underwent mastectomy with or without reconstruction. Fisher's exact tests were used to compare complication rates, with p < 0.05 considered significant. Patients were matched well in terms of demographics. The overall complication rate was 32 % in cohort 1 and 31 % in cohort 2 (p value = 1, Table 1). In cohort 1, 7 of 23 (30 %) patients who underwent immediate expander/implant reconstruction had complications, including 2 patients who had explantation of their reconstructions. In cohort 2, 0 of 8 (0 %) had complications (p value = 0.15). Nearly a third of patients undergoing NAC with AC/T with or without bev developed a postoperative complication after mastectomy. The use of bev was not associated with a significant increase in surgical complications, although this is a nonrandomized data set with a small sample size. As larger data sets become available with the use of neoadjuvant bevacizumab with mastectomy, further refinement may be necessary. C1 [Kansal, Kari Joanne; Dominici, Laura Stewart; Jiang, Wei; Golshan, Mehra] Brigham & Womens Hopspital, Boston, MA USA. [Tolaney, Sara M.; Brock, Jane E.; Winer, Eric P.; Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Isakoff, Steven J.; Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kansal, KJ (reprint author), Brigham & Womens Hopspital, Boston, MA USA. EM karikansal@gmail.com RI JIANG, WEI /F-3930-2015 NR 18 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2013 VL 141 IS 2 BP 255 EP 259 DI 10.1007/s10549-013-2682-z PG 5 WC Oncology SC Oncology GA 226BF UT WOS:000325008500011 PM 24026859 ER PT J AU Berkey, CS Willett, WC Tamimi, RM Rosner, B Frazier, AL Colditz, GA AF Berkey, Catherine S. Willett, Walter C. Tamimi, Rulla M. Rosner, Bernard Frazier, A. Lindsay Colditz, Graham A. TI Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Childhood diet; Vegetable protein; Vegetable fat; Peanut butter; BBD; Prospective ID ASIAN-AMERICAN WOMEN; CANCER RISK; LIFE-STYLE; DIET; CONSUMPTION; QUESTIONNAIRE; VALIDATION; PREVENTION; HORMONES; HEALTH AB Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9-15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996-2001) obtained intake data on a variety of foods. Beginning in 2005, women (18-30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53-0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13-0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43-0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16-0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women. C1 [Berkey, Catherine S.; Tamimi, Rulla M.; Rosner, Bernard] Brigham & Womens Hosp, Dept Med, Channing Div, Med Network, Boston, MA 02115 USA. [Berkey, Catherine S.; Tamimi, Rulla M.; Rosner, Bernard] Harvard Univ, Sch Med, Boston, MA USA. [Berkey, Catherine S.] Channing Div, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. RP Berkey, CS (reprint author), Channing Div, 181 Longwood Ave, Boston, MA 02115 USA. EM catherine.berkey@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU Breast Cancer Research Foundation (NYC, NY); National Institutes of Health (Bethesda, MD) [DK046834]; American Institute for Cancer Research; American Cancer Society Clinical Research Professorship FX This study was supported by a grant from The Breast Cancer Research Foundation (NYC, NY) and by DK046834 from the National Institutes of Health (Bethesda, MD). Dr. Frazier was supported by an award from the American Institute for Cancer Research. Dr. Colditz was supported, in part, by an American Cancer Society Clinical Research Professorship. The authors appreciate the ongoing, since 1996, dedication of our female GUTS participants. NR 37 TC 10 Z9 10 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2013 VL 141 IS 2 BP 299 EP 306 DI 10.1007/s10549-013-2686-8 PG 8 WC Oncology SC Oncology GA 226BF UT WOS:000325008500016 PM 24043428 ER PT J AU John, EM McGuire, V Thomas, D Haile, R Ozcelik, H Milne, RL Felberg, A West, DW Miron, A Knight, JA Terry, MB Daly, M Buys, SS Andrulis, IL Hopper, JL Southey, MC Giles, GG Apicella, C Thorne, H Whittemore, AS AF John, Esther M. McGuire, Valerie Thomas, Duncan Haile, Robert Ozcelik, Hilmi Milne, Roger L. Felberg, Anna West, Dee W. Miron, Alexander Knight, Julia A. Terry, Mary Beth Daly, Mary Buys, Saundra S. Andrulis, Irene L. Hopper, John L. Southey, Melissa C. Giles, Graham G. Apicella, Carmel Thorne, Heather Whittemore, Alice S. CA Kathleen Cuningham Fdn Consortium TI Diagnostic Chest X-Rays and Breast Cancer Risk before Age 50 Years for BRCA1 and BRCA2 Mutation Carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MEDICAL RADIATION-EXPOSURE; CONTRALATERAL BREAST; FAMILY REGISTRY; GENETIC EPIDEMIOLOGY; IONIZING-RADIATION; YOUNG-WOMEN; COHORT; RESOURCE; FLUOROSCOPY; MAMMOGRAPHY AB Background: The effects of low-dose medical radiation on breast cancer risk are uncertain, and few studies have included genetically susceptible women, such as those who carry germline BRCA1 and BRCA2 mutations. Methods: We studied 454 BRCA1 and 273 BRCA2 mutation carriers ages younger than 50 years from three breast cancer family registries in the United States, Canada, and Australia/New Zealand. We estimated breast cancer risk associated with diagnostic chest X-rays by comparing mutation carriers with breast cancer (cases) with those without breast cancer (controls). Exposure to chest X-rays was self-reported. Mammograms were not considered in the analysis. Results: After adjusting for known risk factors for breast cancer, the ORs for a history of diagnostic chest X-rays, excluding those for tuberculosis or pneumonia, were 1.16 [95% confidence interval (CI), 0.64-2.11] for BRCA1 mutations carriers and 1.22 (95% CI, 0.62-2.42) for BRCA2 mutations carriers. The OR was statistically elevated for BRCA2 mutation carriers with three to five diagnostic chest X-rays (P = 0.01) but not for those with six or more chest X-rays. Few women reported chest fluoroscopy for tuberculosis or chest X-rays for pneumonia; the OR estimates were elevated, but not statistically significant, for BRCA1 mutation carriers. Conclusions: Our findings do not support a positive association between diagnostic chest X-rays and breast cancer risk before the ages of 50 years for BRCA1 or BRCA2 mutation carriers. Impact: Given the increasing use of diagnostic imaging involving higher ionizing radiation doses, further studies of genetically predisposed women are warranted. (C) 2013 AACR. C1 [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [John, Esther M.; McGuire, Valerie; Felberg, Anna; West, Dee W.; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA USA. [Haile, Robert] Stanford Univ, Div Oncol, Dept Med, Sch Med, Stanford, CA USA. [Thomas, Duncan] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ozcelik, Hilmi; Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Prosserman Ctr Hlth Res, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Ozcelik, Hilmi] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Milne, Roger L.; Hopper, John L.; Giles, Graham G.; Apicella, Carmel] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Thorne, Heather] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Miron, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Terry, Mary Beth] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Daly, Mary] Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19111 USA. [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP John, EM (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA. EM esther.john@cpic.org RI Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; Whittemore, Alice/F-9925-2014; OI Giles, Graham/0000-0003-4946-9099 FU National Cancer Institute [RO1 CA097359, UM1 CA164920]; National Health and Medical Research Council of Australia; South Wales Cancer Council; Victorian Health Promotion Foundation; Victorian Breast Cancer Research Consortium; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer Council of South Australia; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508] FX This study was supported by the National Cancer Institute grant RO1 CA097359 (to A. S. Whittemore). The Breast Cancer Family Registry (BCFR) is supported by National Cancer Institute grant UM1 CA164920 (to I. L. Andrulis, S. S. Buys, M. Daly, J.L. Hopper, E. M. John, M. B. Terry). The Australian site of the BCFR was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, and the Victorian Breast Cancer Research Consortium. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia (to J.F. Sambrook). The Clinical Follow-UpStudy is funded by NHMRC grants 145684, 288704 and 454508 (to J.F. Sambrook). NR 39 TC 9 Z9 9 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2013 VL 22 IS 9 BP 1547 EP 1556 DI 10.1158/1055-9965.EPI-13-0189 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 221QV UT WOS:000324674500008 PM 23853209 ER PT J AU Wernli, KJ Kitahara, CM Tamers, SL Al-Temimi, MH Braithwaite, D AF Wernli, Karen J. Kitahara, Cari M. Tamers, Sara L. Al-Temimi, Mohammed H. Braithwaite, Dejana TI Undertaking Cancer Research in International Settings: Report from the American Society for Preventive Oncology Special Interest Group on International Issues in Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEALTH RECORDS REGISTER; STRESSFUL LIFE EVENTS; COHORT PROFILE; ALCOHOL; HEIGHT AB The mission of the American Society for Preventive Oncology Special Interest Group in International Issues in Cancer is to serve as a worldwide cancer prevention resource. At the 2013 annual meeting, we presented three early career investigators who conducted research with international collaborators as part of postdoctoral studies. We present a synopsis of each of the scientific presentations. The investigators also highlight useful strategies to encourage a more successful international collaboration, including seeking out existing collaborations between colleagues and international researchers, maintaining awareness and sensitivity of cultural norms, establishing clear communication about investigator roles and expectations, and persevering in the face of potential challenges due to the nature of these collaborations. Incorporation of these key elements could prove useful for researchers interested in pursuing cross-country projects. (C) 2013 AACR. C1 [Wernli, Karen J.] Grp Hlth Res Inst, Seattle, WA USA. [Kitahara, Cari M.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Tamers, Sara L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Al-Temimi, Mohammed H.] Univ Utah, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT USA. [Braithwaite, Dejana] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. RP Braithwaite, D (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA. EM DBraithwaite@epi.ucsf.edu RI Kitahara, Cari/R-8267-2016 FU Agency for Healthcare Research and Quality K12 Comparative Effectiveness Research Scholar Award [K12 HS019482]; Intramural Research Program of the National Cancer Institute (NCI), NIH; NIH/NCI Harvard Education Program in Cancer Prevention and Control [R25 CA057713]; NIH/NCI Reducing Social Disparities in Cancer Risk [K05 CA108663-05]; European Commission Public Health Programme, DG Sanco [2006 319]; American Cancer Society [121891-MRSG-12-007-01-CPHPS] FX K.J. Wernli was supported in part by Agency for Healthcare Research and Quality K12 Comparative Effectiveness Research Scholar Award (K12 HS019482). C. M. Kitahara was supported in part by the Intramural Research Program of the National Cancer Institute (NCI), NIH. S. L. Tamers was supported in part by the NIH/NCI Harvard Education Program in Cancer Prevention and Control (R25 CA057713; PI G. Sorensen), and the NIH/NCI Reducing Social Disparities in Cancer Risk (K05 CA108663-05 to GS). The work of M. H. Al-Temimi was part of the Women in Europe against Lung Cancer and Smoking (WELAS) project, which was supported by the European Commission Public Health Programme, DG Sanco (Grant # 2006 319). D. Braithwaite was supported in part by Grant # 121891-MRSG-12-007-01-CPHPS from the American Cancer Society. NR 20 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2013 VL 22 IS 9 BP 1638 EP 1641 DI 10.1158/1055-9965.EPI-13-0655 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 221QV UT WOS:000324674500019 PM 23845714 ER PT J AU O'Regan, KN Shinagare, AB Saboo, SS Ramaiya, NH Jagannathan, JP Tirumani, SH AF O'Regan, Kevin N. Shinagare, Atul B. Saboo, Sachin S. Ramaiya, Nikhil H. Jagannathan, Jyothi P. Tirumani, Sree Harsha TI Gastrointestinal stromal tumors (GIST): lesser known facts SO CLINICAL IMAGING LA English DT Review DE Gastrointestinal stromal tumor; Tumor biology; Molecular classification; Atypical metastases; Syndromes associated with GIST ID MOLECULAR TARGETED THERAPY; RADIOLOGISTS; METASTASIS; MANAGEMENT; MUTATIONS; IMATINIB; FEATURES; STOMACH; SERIES AB In an era of molecular targeted therapy, patients with advanced gastrointestinal stromal tumor (GIST) are living longer and are often followed with imaging. Therefore, it is important for the radiologists to be aware of the atypical subtypes of GIST, implications of molecular makeup, its behavior, and the uncommon metastatic sites. The aim of this pictorial review is to illustrate the lesser-known aspects of GIST including histological and molecular classifications, syndromes associated with GIST, and uncommon metastatic sites. (C) 2013 Elsevier Inc. All rights reserved. C1 [O'Regan, Kevin N.] Cork Univ Hosp, Dept Radiol, Cork, Ireland. [Shinagare, Atul B.; Saboo, Sachin S.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.; Tirumani, Sree Harsha] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Ramaiya, Nikhil H.; Jagannathan, Jyothi P.; Tirumani, Sree Harsha] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM stirumani@partners.org NR 25 TC 6 Z9 6 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD SEP-OCT PY 2013 VL 37 IS 5 BP 821 EP 829 DI 10.1016/j.clinimag.2013.04.005 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 220TS UT WOS:000324610400003 PM 23845255 ER PT J AU Delaney-Busch, N Kuperberg, G AF Delaney-Busch, Nathaniel Kuperberg, Gina TI Friendly drug-dealers and terrifying puppies: Affective primacy can attenuate the N400 effect in emotional discourse contexts SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE Discourse; Emotion; ERP; N400; Late positivity; Language ID LATENT SEMANTIC ANALYSIS; EVENT-RELATED POTENTIALS; MEDIAL TEMPORAL-LOBE; BRAIN POTENTIALS; LANGUAGE COMPREHENSION; ERP EVIDENCE; FIELD POTENTIALS; SENTENCE; MEMORY; KNOWLEDGE AB Words that are semantically congruous with their preceding discourse context are easier to process than words that are semantically incongruous with their context. This facilitation of semantic processing is reflected by an attenuation of the N400 event-related potential (ERP). We asked whether this was true of emotional words in emotional contexts where discourse congruity was conferred through emotional valence. ERPs were measured as 24 participants read two-sentence scenarios with critical words that varied by emotion (pleasant, unpleasant, or neutral) and congruity (congruous or incongruous). Semantic predictability, constraint, and plausibility were comparable across the neutral and emotional scenarios. As expected, the N400 was smaller to neutral words that were semantically congruous (vs. incongruous) with their neutral discourse context. No such N400 congruity effect was observed on emotional words following emotional discourse contexts. Rather, the amplitude of the N400 was small to all emotional words (pleasant and unpleasant), regardless of whether their emotional valence was congruous with the valence of their emotional discourse context. However, consistent with previous studies, the emotional words produced a larger late positivity than did the neutral words. These data suggest that comprehenders bypassed deep semantic processing of valence-incongruous emotional words within the N400 time window, moving rapidly on to evaluate the words' motivational significance. C1 [Delaney-Busch, Nathaniel; Kuperberg, Gina] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kuperberg, Gina] Massachusetts Gen Hosp, Dept Psychiat, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Delaney-Busch, N (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM Nathaniel.Delaney-Busch@tufts.edu FU NIMH [R01 MH071635]; NARSAD; Tufts University; Sidney Baer Trust FX This work was supported by NIMH Grant No. R01 MH071635 and by NARSAD (with the Sidney Baer Trust), as well as by a Senior Faculty Research Award from Tufts University to G. K. We thank several individuals who contributed to the experimental materials and data collection, including Arim Choi, Kana Okano, Vivian Haime, and Gianna Wilkie. We also thank Eric Fields, Martin Paczynski, and our reviewers for their insightful comments and help with interpretation. NR 80 TC 16 Z9 16 U1 3 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2013 VL 13 IS 3 BP 473 EP 490 DI 10.3758/s13415-013-0159-5 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 220CI UT WOS:000324557900005 PM 23559312 ER PT J AU Yi, BA Mummery, CL Chien, KR AF Yi, B. Alexander Mummery, Christine L. Chien, Kenneth R. TI Direct Cardiomyocyte Reprogramming: A New Direction for Cardiovascular Regenerative Medicine SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC FIBROBLASTS; DEFINED FACTORS; STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; HEART-TISSUE; REPAIR; DIFFERENTIATION; THERAPY; PROGENITORS AB The past few years have seen unexpected new developments in direct cardiomyocyte reprogramming. Direct cardiomyocyte reprogramming potentially offers an entirely novel approach to cardiovascular regenerative medicine by converting cardiac fibroblasts into functional cardiomyocytes in situ. There is much to be learned, however, about the mechanisms of direct reprogramming in order that the process can be made more efficient. Early efforts have suggested that this new technology can be technically challenging. Moreover, new methods of inducing heart reprogramming will need to be developed before this approach can be translated to the bedside. Despite this, direct cardiomyocyte reprogramming may lead to new therapeutic options for sufferers of heart disease. C1 [Yi, B. Alexander] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Mummery, Christine L.] Leiden Univ, Med Ctr, Dept Anat & Embryol, NL-2300 RC Leiden, Netherlands. [Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Chien, Kenneth R.] Karolinska Inst, Dept Cell & Mol Biol & Med, SE-17177 Stockholm, Sweden. RP Yi, BA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM byi@partners.org FU American Heart Association [12FTF11820037]; Harvard Stem Cell Institute; CVON-HUSTCARE Programme of the Netherlands Heart Foundation FX The authors thank Emil Hansson for thoughtful comments on the manuscript. B.A.Y. is supported by an award from the American Heart Association (12FTF11820037) and the Harvard Stem Cell Institute. C.L.M. is supported by the CVON-HUSTCARE Programme of the Netherlands Heart Foundation. NR 36 TC 8 Z9 9 U1 2 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD SEP PY 2013 VL 3 IS 9 AR a014050 DI 10.1101/cshperspect.a014050 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227EV UT WOS:000325093800001 PM 24003244 ER PT J AU Boudreaux, ED Miller, I Goldstein, AB Sullivan, AF Allen, MH Manton, AP Arias, SA Camargo, CA AF Boudreaux, Edwin D. Miller, Ivan Goldstein, Amy B. Sullivan, Ashley F. Allen, Michael H. Manton, Anne P. Arias, Sarah A. Camargo, Carlos A., Jr. TI The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE): Method and design considerations SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Suicide; Research methods; Mental health; Emergency department ID SUICIDAL-BEHAVIOR; INTERVENTION RESEARCH; RISK; HEALTH; PREVALENCE; THOUGHTS; FIREARMS; SYSTEM AB Background: Due to the concentration of individuals at-risk for suicide, an emergency department visit represents an opportune time for suicide risk screening and intervention. Purpose: The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) uses a quasi-experimental, interrupted time series design to evaluate whether (1) a practical approach to universally screening ED patients for suicide risk leads to improved detection of suicide risk and (2) a multi-component intervention delivered during and after the ED visit improves suicide-related outcomes. Methods: This paper summarizes the ED-SAFE's study design and methods within the context of considerations relevant to effectiveness research in suicide prevention and pertinent human participants concerns. 1440 suicidal individuals, from 8 general ED's nationally will be enrolled during three sequential phases of data collection (480 individuals/phase): (1) Treatment as Usual; (2) Universal Screening; and (3) Intervention. Data from the three phases will inform two separate evaluations: Screening Outcome (Phases 1 and 2) and Intervention (Phases 2 and 3). Individuals will be followed for 12 months. The primary study outcome is a composite reflecting completed suicide, attempted suicide, aborted or interrupted attempts, and implementation of rescue procedures during an outcome assessment. Conclusions: While 'classic' randomized control trials (RCT) are typically selected over quasi-experimental designs, ethical and methodological issues may make an RCT a poor fit for complex interventions in an applied setting, such as the ED. ED-SAFE represents an innovative approach to examining the complex public health issue of suicide prevention through a multi-phase, quasi-experimental design embedded in 'real world' clinical settings. (C) 2013 Elsevier Inc. All rights reserved. C1 [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Miller, Ivan] Butler Hosp, Providence, RI 02906 USA. [Goldstein, Amy B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Goldstein, Amy B.] NIMH, Div Serv & Intervent Res, NIH, Bethesda, MD 20892 USA. [Sullivan, Ashley F.; Arias, Sarah A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Allen, Michael H.] Univ Colorado, Depress Ctr, Aurora, CO USA. [Allen, Michael H.] VISN 19 MIRECC, Aurora, CO USA. [Manton, Anne P.] Cape Cod Hosp, Cape Psychiat Ctr, Cape Cod, MA USA. RP Boudreaux, ED (reprint author), Univ Massachusetts, Sch Med, LA 189,55 Lake Ave North, Worcester, MA 01655 USA. EM Edwin.Boudreaux@umassmed.edu RI Allen, Michael/A-8776-2011; OI Boudreaux, Edwin/0000-0002-3223-6371; Arias, Sarah/0000-0003-1832-8824 FU National Institute on Mental Health [U01MH088278] FX The project described was supported by Award Number U01MH088278 from the National Institute on Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. None of the authors have financial conflicts of interest to disclose. NR 26 TC 16 Z9 16 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2013 VL 36 IS 1 BP 14 EP 24 DI 10.1016/j.cct.2013.05.008 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 225KH UT WOS:000324961300002 PM 23707435 ER PT J AU Sonne, SC Andrews, JO Gentilin, SM Oppenheimer, S Obeid, J Brady, K Wolf, S Davis, R Magruder, K AF Sonne, Susan C. Andrews, Jeannette O. Gentilin, Stephanie M. Oppenheimer, Stephanie Obeid, Jihad Brady, Kathleen Wolf, Sharon Davis, Randal Magruder, Kathryn TI Development and pilot testing of a video-assisted informed consent process SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Informed consent process; Videos; Electronic forms; Tablet computing ID RANDOMIZED CONTROLLED-TRIAL; COMPREHENSION; INFORMATION; MULTIMEDIA; LITERACY AB The informed consent process for research has come under scrutiny, as consent documents are increasingly long and difficult to understand. Innovations are needed to improve comprehension in order to make the consent process truly informed. We report on the development and pilot testing of video clips that could be used during the consent process to better explain research procedures to potential participants. Based on input from researchers and community partners, 15 videos of common research procedures/concepts were produced. The utility of the videos was then tested by embedding them in mock-informed consent documents that were presented via an online electronic consent system designed for delivery via iPad. Three mock consents were developed, each containing five videos. All participants (n = 61) read both a paper version and the video-assisted iPad version of the same mock consent and were randomized to which format they reviewed first. Participants were given a competency quiz that posed specific questions about the information in the consent after reviewing the first consent document to which they were exposed. Most participants (78.7%) preferred the video-assisted format compared to paper (12.9%). Nearly all (96.7%) reported that the videos improved their understanding of the procedures described in the consent document; however, the comprehension of material did not significantly differ by consent format. Results suggest videos may be helpful in providing participants with information about study procedures in a way that is easy to understand. Additional testing of video consents for complex protocols and with subjects of lower literacy is warranted. (C) 2013 Elsevier Inc. All rights reserved. C1 [Sonne, Susan C.; Andrews, Jeannette O.; Gentilin, Stephanie M.; Oppenheimer, Stephanie; Obeid, Jihad; Brady, Kathleen; Wolf, Sharon; Davis, Randal; Magruder, Kathryn] Med Univ S Carolina, Charleston, SC 29425 USA. [Brady, Kathleen; Magruder, Kathryn] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Sonne, SC (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 125 Doughty St,Suite 190, Charleston, SC 29425 USA. EM sonnesc@musc.edu OI Obeid, Jihad/0000-0002-7193-7779 FU South Carolina Clinical and Translational Research (SCTR) Institute; Medical University of South Carolina, through NIH [UL1 RR029882, UL1 TR000062]; [RC2 LM010796] FX This publication was supported by the South Carolina Clinical and Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, through NIH grant numbers UL1 RR029882 and UL1 TR000062 as well as RC2 LM010796. NR 18 TC 9 Z9 9 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2013 VL 36 IS 1 BP 25 EP 31 DI 10.1016/j.cct.2013.05.011 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 225KH UT WOS:000324961300003 PM 23747986 ER PT J AU Trivedi, RB Szarka, JG Beaver, K Brousseau, K Nevins, E Yancy, WS Slade, A Voils, CI AF Trivedi, Ranak B. Szarka, Jackie G. Beaver, Kristine Brousseau, Koriann Nevins, Elaine Yancy, William S., Jr. Slade, Alecia Voils, Corrine I. TI Recruitment and retention rates in behavioral trials involving patients and a support person: A systematic review SO CONTEMPORARY CLINICAL TRIALS LA English DT Review DE Dyad; Caregiver; Couple; Intervention; Recruitment; Retention ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; CANCER PAIN MANAGEMENT; BREAST-CANCER; FAMILY CAREGIVERS; ALZHEIMER-DISEASE; CLINICAL-TRIAL; BRAIN-INJURY; STROKE PATIENTS; INTERVENTION AB Background: Recruitment and retention challenges impede the study of behavioral interventions among patient-support person dyads. Purpose: The aim of the study was to characterize recruitment and retention rates of behavioral interventions involving dyads. Methods: Using PRISMA guidelines and with the guidance of a medical librarian, we searched Medline, EMBASE, Cochrane Controlled Trials, PsycInfo, and CINAHL from inception until July 2011. Eligible articles involved RCTs of behavioral interventions targeting adult patients with a non-psychiatric illness and a support person. Sample and study characteristics, recruitment and retention strategies, and recruitment and retention rates were abstracted in duplicate. Quality of reporting was determined on a 5-point scale. Due to the heterogeneity in data reporting and missing data, a narrative synthesis was undertaken Results: 53 unique studies involving 8081 dyads were included. 9 studies were ascertained to have a "high quality" of reporting. A majority of the studies did not report target sample size, time to complete recruitment, and sample sizes at each follow-up time point. Strategies employed to recruit support persons were rarely reported. 16 studies did not report the number of dyads screened. The mean recruitment rate was 51.2% (range: 4.3%-95.4%), and mean retention rate was 77.5% (range: 36%-100%). Conclusions: Details regarding recruitment and retention methodology were sparse in these interventions. Where available, data suggests that resources need to be devoted towards recruitment of sample but that retention rates are generally adequate. Published by Elsevier Inc. C1 [Trivedi, Ranak B.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Trivedi, Ranak B.; Szarka, Jackie G.; Beaver, Kristine; Brousseau, Koriann; Nevins, Elaine] VA Puget Sound Hlth Care Syst, Northwest HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Yancy, William S., Jr.; Slade, Alecia; Voils, Corrine I.] Ctr Hlth Serv Res Primary Care, Dept Vet Affairs, Durham, NC 27705 USA. [Yancy, William S., Jr.; Voils, Corrine I.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Trivedi, RB (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat MPD 152, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM ranak.trivedi@va.gov; Jackie.szarka@va.gov; kaakullia@gmail.com; Koriann.brousseau@va.gov; Elaine.nevins@va.gov; Yancy006@mc.duke.edu; Alecia.slade@gmail.com; voils001@mc.duke.edu OI Voils, Corrine/0000-0003-1913-663X FU Department of Veterans Affairs (VA); Veterans Health Administration Health Services Research and Development (HSRD) Service, IHI [IHI 02-062]; VA HSR&D Career Development Award [CDA-09-206] FX This work was supported by the Department of Veterans Affairs (VA), Veterans Health Administration Health Services Research and Development (HSR&D) Service, IHI 02-062. Dr. Trivedi was supported by a VA HSR&D Career Development Award, CDA-09-206. VA Puget Sound Health Care System and the VA Palo Alto Health Care System provided resources to support this research. The authors 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. Views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 68 TC 6 Z9 6 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2013 VL 36 IS 1 BP 307 EP 318 DI 10.1016/j.cct.2013.07.009 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 225KH UT WOS:000324961300034 PM 23916918 ER PT J AU Cea, M Cagnetta, A Nencioni, A Gobbi, M Patrone, F AF Cea, Michele Cagnetta, Antonia Nencioni, Alessio Gobbi, Marco Patrone, Franco TI New Insights Into Biology of Chronic Myeloid Leukemia: Implications in Therapy SO CURRENT CANCER DRUG TARGETS LA English DT Article DE Autophagy; BCR-ABL; chronic myeloid leukemia; genomic instability; intracellular signaling; leukemia stem cell ID CHRONIC MYELOGENOUS LEUKEMIA; CANCER STEM-CELLS; HEDGEHOG PATHWAY ACTIVATION; CHROMOSOME-POSITIVE CELLS; COLONY-STIMULATING FACTOR; DNA-BINDING ACTIVITY; BLAST-CRISIS CML; BCR-ABL; CHRONIC-PHASE; PHILADELPHIA-CHROMOSOME AB Over the past decades the prognosis of patients with Chronic Myeloid Leukemia (CML) has radically changed due to groundbreaking scientific and translational studies that have revealed the biologic basis of such a hematologic malignancy. These studies have led to the rapid development of many BCR-ABL specific tyrosine kinase inhibitors (TKIs), such as Imatinib, Nilotinib and Dasatinib, which have improved 10-years survival to more than 80%. Although these therapies represent a landmark step in the race for the cure of CML, they did not change the progression in advanced phase of disease. Therefore unravel the molecular mechanisms and the biological basis of CML, especially during the advanced stage, is of seminal importance as this would result in the design of more effective and less toxic therapies. In such a scenario, several novel drugs designed to specifically target biological features of CML cells are currently in clinical trials with promising results that would provide not only improve the therapeutic armamentarium but also to overcome drug resistance of this tumor. Here we review recent advances in biology of CML and their therapeutic implications. C1 [Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cea, Michele; Cagnetta, Antonia; Gobbi, Marco] IRCCS AOU San Martino IST, Dept Hematol & Oncol, Genoa, Italy. [Nencioni, Alessio; Patrone, Franco] IRCCS AOU San Martino IST, Dept Internal Med, Genoa, Italy. RP Cea, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M551,450 Brookline Ave, Boston, MA 02115 USA. EM michele_cea@dfci.harvard.edu FU American Italian Cancer Foundation; Fondazione Italiana per la Ricerca sul Cancro; Associazione Cristina Bassi; Associazione Italiana per la Ricerca sul Cancro FX This study is supported by American Italian Cancer Foundation and Fondazione Italiana per la Ricerca sul Cancro (M. C.); Associazione Cristina Bassi (A.C.) NR 146 TC 5 Z9 6 U1 2 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD SEP PY 2013 VL 13 IS 7 BP 711 EP 723 PG 13 WC Oncology SC Oncology GA 224DF UT WOS:000324861500002 PM 23906052 ER PT J AU Adamia, S Pilarski, PM Bar-Natan, M Stone, RM Griffin, JD AF Adamia, Sophia Pilarski, Patrick M. Bar-Natan, Michal Stone, Richard M. Griffin, James D. TI Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target? SO CURRENT CANCER DRUG TARGETS LA English DT Article DE Alternative splicing; BCR-ABL; bio-markers; chronic myeloid leukemia; therapeutic targets ID PRE-MESSENGER-RNA; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; SYNTHASE KINASE 3-BETA; HUMAN BREAST-CANCER; TRANSCRIPTION FACTOR; TUMOR-SUPPRESSOR; FRASIER-SYNDROME; BLAST-CRISIS AB Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killing of residual leukaemic stem cells. There is need to identify alternative selective molecular targets for this disease and develop more effective therapeutic approaches. Alternative pre-mRNA splicing (AS) is an epigenetic process that greatly diversifies the repertoire of the transcriptome. AS orchestrates interactions between various types of proteins and between proteins and nucleic acids. Changes caused by individual splicing events in the cells are small, however, "splicing programs" typically react to these individual changes with considerable effects in cell proliferation, cell survival, and apoptosis. Current evidence suggests a pivotal role of AS in leukemias, particularly in myelodisplastic syndrome (MDS) and chronic lymphocyte leukemia (CLL). From these studies and studies in other malignances, it is clear that splicing abnormalities play a significant role in malignant transformation. Evaluation of AS events in CML can be used to identify novel disease markers and drug-sensitive targets to overcome the limits of the small molecule inhibitors currently used for treating patients with CML. The use of aberrant splice variants as disease markers has been reported, however, little is known about the use of splicing abnormalities as drug targets in CML. Herein we discuss potential therapeutic approaches that can be used to target splicing abnormalities in CML. C1 [Adamia, Sophia; Stone, Richard M.; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pilarski, Patrick M.] Univ Alberta, Dept Comp Sci, Edmonton, AB T6G 2M7, Canada. [Bar-Natan, Michal] Beilinson Med Ctr, Davidoff Canc Ctr, Inst Hematol, Rabin Med Ctr, Petah Tiqwa, Israel. RP Adamia, S (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Sophia_adamia@dfci.harvard.edu FU ASH; LLS (Leukemia & Lymphoma Society) Translational Research Program (LLS-TRP); Alberta Innovates Centre for Machine Learning; Alberta Innovates - Technology Futures; Davidoff Cancer Center; Rabin Medical Center; Dana Farber Cancer Institute (DFCI); NIH [CA66996]; LLS-TRP; DFCI FX SA is supported by an ASH scholar award for Clinical/Translational Research Fellows and LLS (Leukemia & Lymphoma Society) Translational Research Program (LLS-TRP) grant to JDG and SA; PMP is funded by the Alberta Innovates Centre for Machine Learning, and Alberta Innovates - Technology Futures. MBN was supported by the Davidoff Cancer Center and Rabin Medical Center; RMS is supported by the Dana Farber Cancer Institute (DFCI); JDG is supported by the NIH CA66996, LLS-TRP, and DFCI. NR 156 TC 6 Z9 8 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD SEP PY 2013 VL 13 IS 7 BP 735 EP 748 PG 14 WC Oncology SC Oncology GA 224DF UT WOS:000324861500004 PM 23906050 ER PT J AU Cagnetta, A Garuti, A Marani, C Cea, M Miglino, M Rocco, I Palermo, C Fugazza, G Cirmena, G Colombo, N Grasso, R Nencioni, A Gobbi, M Patrone, F AF Cagnetta, Antonia Garuti, Anna Marani, Carlo Cea, Michele Miglino, Maurizio Rocco, Ilaria Palermo, Claudia Fugazza, Giuseppina Cirmena, Gabriella Colombo, Nicoletta Grasso, Raffaella Nencioni, Alessio Gobbi, Marco Patrone, Franco TI Evaluating Treatment Response of Chronic Myeloid Leukemia: Emerging Science and Technology SO CURRENT CANCER DRUG TARGETS LA English DT Article DE chronic myelogenous leukemia; cytogenetic analysis; molecular monitoring; minimal residual disease; mutational analysis ID CHRONIC MYELOGENOUS LEUKEMIA; ABL KINASE DOMAIN; IN-SITU HYBRIDIZATION; MINIMAL RESIDUAL DISEASE; PHILADELPHIA-POSITIVE PATIENTS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; BCR-ABL1 TRANSCRIPT LEVELS; IMATINIB MESYLATE THERAPY; POLYMERASE-CHAIN-REACTION AB Chronic myeloid leukemia (CML) is a hematological disease accounting for about 15-20% of all adult leukemias. The clinical and biologic advances achieved in such a malignancy, represent one of the best successes obtained by translational medicine. Indeed, identification of the fusion oncogene BCR-ABL has allowed using of small molecule inhibitors of its tyrosine kinase activity which, in turn, have literally revolutionized the treatment of CML. Importantly the successfully clinical management was also realized on appropriate diagnosis, disease monitoring as well as early identification of such mutations causing drug resistance. Notably the recent availability of refined laboratory equipments represented by the Next Generation Sequencing (NGS) and genomic analyses has further contributed to gain ground towards the cure of this tumor. These issues are discussed here together with an overview on how patients treated with tyrosine kinase inhibitors should be monitored. C1 [Cagnetta, Antonia; Garuti, Anna; Marani, Carlo; Cea, Michele; Miglino, Maurizio; Rocco, Ilaria; Palermo, Claudia; Fugazza, Giuseppina; Cirmena, Gabriella; Colombo, Nicoletta; Grasso, Raffaella; Nencioni, Alessio; Gobbi, Marco; Patrone, Franco] IRCCS AOU San Martino IST, Dept Hematol & Oncol, Genoa, Italy. [Cagnetta, Antonia; Cea, Michele] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Cagnetta, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M551,450 Brookline Ave, Boston, MA 02115 USA. EM antonia_cagnetta@dfci.harvard.edu; anna.garuti@unige.it FU Associazione Cristina Bassi; American Italian Cancer Foundation; Associazione Italiana per la Ricerca sul Cancro [6108]; A.I.L. Sezione Liguria; University of Genoa FX This study is supported by Associazione Cristina Bassi (A. C.); American Italian Cancer Foundation (M. C.); Associazione Italiana per la Ricerca sul Cancro (Code 6108 to A.N.); A.I.L. Sezione Liguria and University of Genoa. NR 109 TC 6 Z9 6 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD SEP PY 2013 VL 13 IS 7 BP 779 EP 790 PG 12 WC Oncology SC Oncology GA 224DF UT WOS:000324861500009 PM 23906053 ER PT J AU Edlow, BL Giacino, JT Wu, O AF Edlow, Brian L. Giacino, Joseph T. Wu, Ona TI Functional MRI and Outcome in Traumatic Coma SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Traumatic brain injury; Traumatic axonal injury; Coma; Functional MRI; Resting-state functional MRI; Arterial spin labeling perfusion MRI; Default mode network; Traumatic coma ID DEFAULT-MODE NETWORK; MINIMALLY CONSCIOUS STATE; SEVERE HEAD-INJURY; PERSISTENT VEGETATIVE STATE; ASCENDING AROUSAL SYSTEM; PLACEBO-CONTROLLED TRIAL; BRAIN-INJURY; RESTING-STATE; SUSTAINED-ATTENTION; PERFUSION FMRI AB Advances in task-based functional MRI (fMRI), resting-state fMRI (rs-fMRI), and arterial spin labeling (ASL) perfusion MRI have occurred at a rapid pace in recent years. These techniques for measuring brain function have great potential to improve the accuracy of prognostication for civilian and military patients with traumatic coma. In addition, fMRI, rs-fMRI, and ASL perfusion MRI have provided novel insights into the pathophysiology of traumatic disorders of consciousness, as well as the mechanisms of recovery from coma. However, functional neuroimaging techniques have yet to achieve widespread clinical use as prognostic tests for patients with traumatic coma. Rather, a broad spectrum of methodological hurdles currently limits the feasibility of clinical implementation. In this review, we discuss the basic principles of fMRI, rs-fMRI, and ASL perfusion MRI and their potential applications as prognostic tools for patients with traumatic coma. We also discuss future strategies for overcoming the current barriers to clinical implementation. C1 [Edlow, Brian L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Giacino, Joseph T.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA 02129 USA. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Edlow, BL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St Lunder 650, Boston, MA 02114 USA. EM bedlow@partners.org; jgiacino@partners.org; ona@nmr.mgh.harvard.edu FU National Institutes of Health [R25NS065743]; Center for Integration of Medicine and Innovative Technology (Boston, MA, USA); National Institute on Disability and Rehabilitation Research, United States Department of Education [H133A120085] FX The contents of this article were developed with support from the National Institutes of Health (R25NS065743), the Center for Integration of Medicine and Innovative Technology (Boston, MA, USA), and the National Institute on Disability and Rehabilitation Research, United States Department of Education (H133A120085; Spaulding-Harvard Traumatic Brain Injury Model System). However, the contents do not necessarily represent the policy of the Department of Education, and endorsement by the federal government should not be assumed. NR 100 TC 7 Z9 9 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD SEP PY 2013 VL 13 IS 9 AR 375 DI 10.1007/s11910-013-0375-y PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221FD UT WOS:000324642300004 PM 23881623 ER PT J AU Fisher, V Fernandez, MP Krejci-Manwaring, J AF Fisher, Valerie Fernandez, Martin P. Krejci-Manwaring, Jennifer TI Lichen Planus Mimicking Recalcitrant Ulcerative Psoriasis: When Is It Time to Biopsy? SO CUTIS LA English DT Article ID EFFICACY AB LP verrucosus, is a rare disorder that presents as verrucous plaques, typically on the lower extremities and ankles. This variant differs from the common presentation of LP, which appears as flat, polygonal, pink-purple papules spread diffusely on the flexor wrists, trunk, shins, and dorsal aspects of the feet, frequently involving the oral mucosa. Clinically, hypertrophic LP can be confused with psoriasis and usually does not respond to therapy with biologics. We present a case of hypertrophic LP in a 42-year-old woman who had been treated extensively for psoriasis. Although the morphology and location of the hyperkeratotic plaques mimicked psoriasis, biopsy results exhibited characteristic features of hypertrophic LP, and the lesions responded to treatment with acitretin,. clobetasol propionate ointment, hydroxychloroquine, and simple wound care. The hypertrophic variant of LP can be extremely challenging to differentiate from psoriasis. Physicians who treat patients with scaly plaques should think beyond psoriasis and consider the hypertrophic variant of LP as a potential diagnosis. C1 [Fisher, Valerie; Fernandez, Martin P.; Krejci-Manwaring, Jennifer] Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, San Antonio, TX 78229 USA. [Krejci-Manwaring, Jennifer] Audie L Murphy Mem Vet Adm Med Ctr, Div Dermatol, San Antonio, TX 78229 USA. RP Krejci-Manwaring, J (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM krejcimanwar@uthscsa.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD SEP PY 2013 VL 92 IS 3 BP 136 EP 139 PG 4 WC Dermatology SC Dermatology GA 223FW UT WOS:000324791100010 PM 24153142 ER PT J AU Wilens, TE Martelon, M Anderson, JP Shelley-Abrahamson, R Biederman, J AF Wilens, Timothy E. Martelon, MaryKate Anderson, Jesse P. Shelley-Abrahamson, Rachel Biederman, Joseph TI Difficulties in emotional regulation and substance use disorders: A controlled family study of bipolar adolescents SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Juvenile bipolar disorder; Substance use disorders; Dysregulation; CBCL; Child Behavior Checklist; Deficits in emotional self-regulation; DESR; Adolescents; Bipolar disorder; BD; Cigarettes; Tobacco ID CHILD-BEHAVIOR CHECKLIST; INTERVIEW-DERIVED DIAGNOSIS; 1ST HOSPITALIZATION; YOUNG-ADULTS; CLINICAL CHARACTERISTICS; LONGITUDINAL ANALYSIS; SPECTRUM DISORDERS; PROFILE PREDICTS; CANNABIS USE; I DISORDER AB Background: Self-regulatory mechanisms appear etiologically operant in the context of both substance use disorders (SUD) and bipolar disorder (BD), however, little is known about the role of deficits in emotional self-regulation (DESR) as it relates to SUD in context to mood dysregulation. To this end, we examined to what extent DESR was associated with SUD in a high-risk sample of adolescents with and without BD. Methods: 203 families were assessed with a structured psychiatric interview. Using the Child Behavior Checklist (CBCL), a subject was considered to have DESR when he or she had an average elevation of 1 standard deviation (SD) above the norm on 3 clinical scale T scores (attention, aggression, and anxiety/depression; scores: 60 x 3 >= 180). Results: Among probands and siblings with CBCL data (N=303), subjects with DESR were more likely to have any SUD, alcohol use disorder, drug use disorder, and cigarette smoking compared to subjects with scores <180 (all p values <0.001), even when correcting for BD. We found no significant differences in the risk of any SUD and cigarette smoking between those with 1SD and 2SD above the mean (all p values >0.05). Subjects with cigarette smoking and SUD had more DESR compared to those without these disorders. Conclusions: Adolescents with DESR are more likely to smoke cigarettes and have SUD. More work is needed to explore DESR in longitudinal samples. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Wilens, Timothy E.; Martelon, MaryKate; Anderson, Jesse P.; Shelley-Abrahamson, Rachel; Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy E.; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Parkman St,YAW 6A, Boston, MA 02114 USA. EM twilens@partners.org FU NIH [R01 DA12945, K24 DA016264] FX Funding for this study was provided by NIH R01 DA12945 (T.W.) and K24 DA016264 (T.W.); the NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 55 TC 8 Z9 9 U1 2 U2 18 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2013 VL 132 IS 1-2 BP 114 EP 121 DI 10.1016/j.drugalcdep.2013.01.015 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 216KE UT WOS:000324281400016 PM 23422834 ER PT J AU Ghose, T Fiellin, DA Gordon, AJ Metraux, S Goetz, MB Blackstock, O McInnes, K Rodriguez-Barradas, MC Justice, AC AF Ghose, T. Fiellin, D. A. Gordon, A. J. Metraux, S. Goetz, M. B. Blackstock, O. McInnes, K. Rodriguez-Barradas, M. C. Justice, A. C. TI Hazardous drinking and its association with homelessness among veterans in care SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Hazardous drinking; Homelessness; Veteran care; Alcohol use; Longitudinal analysis; Veterans Aging Cohort Study ID DSM-III-R; ALCOHOL-USE; SUBSTANCE-ABUSE; MENTAL-ILLNESS; HEALTH-CARE; GENERAL-POPULATION; SUICIDAL IDEATION; WAR VETERANS; DRUG-ABUSE; DRINKERS AB Background: While scholarship on alcohol use and homelessness has focused on the impact of alcohol abuse and dependence, little is known about the effects of lower levels of misuse such as hazardous use. Veterans receiving care in the Department of Veterans Affairs Health Care System (VA) constitute a population that is vulnerable to alcohol misuse and homelessness. This research examines the effects of hazardous drinking on homelessness in the Veterans Aging Cohort Study, a sample of 2898 older veterans (mean age=50.2), receiving care in 8 VAs across the country. Methods: Logistic regression models examined the associations between (1) hazardous drinking at baseline and homelessness at 1-year follow-up, (2) transitions into and out of hazardous drinking from baseline to follow-up and homelessness at follow-up, and (3) transitioning to hazardous drinking and transitioning to homelessness from baseline to follow-up during that same time-period. Results: After controlling for other correlates including alcohol dependence, hazardous drinking at baseline increased the risk of homelessness at follow-up (adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI] = 1.02, 1.88). Transitioning to hazardous drinking more than doubled the risk of homelessness at follow-up (AOR=2.42,95% CI=1.41, 4.15), while more than doubling the risk of transitioning from being housed at baseline to being homeless at follow-up (AOR=2.49, 95% CI=1.30, 4.79). Conclusions: Early intervention that seeks to prevent transitioning into hazardous drinking could increase housing stability among veterans. Brief interventions which have been shown to be effective at lower levels of alcohol use should be implemented with veterans in VA care. Published by Elsevier Ireland Ltd. C1 [Ghose, T.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19130 USA. [Fiellin, D. A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Fiellin, D. A.] Yale Univ, Sch Med, Ctr Interdisciplinary Res AIDS, New Haven, CT 06510 USA. [Gordon, A. J.] Univ Pittsburgh, Sch Med, VA Pittsburgh HealthCare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Metraux, S.] Univ Sci, Dept Hlth Policy & Publ Hlth, Philadelphia, PA 19104 USA. [Goetz, M. B.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Blackstock, O.; Justice, A. C.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Blackstock, O.; Justice, A. C.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [McInnes, K.] ENRM VA Med Ctr, VA QUERI Program, Bedford, MA 01730 USA. [McInnes, K.] ENRM VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [McInnes, K.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Rodriguez-Barradas, M. C.] Michael E DeBakey VAMC, Houston, TX 77030 USA. [Rodriguez-Barradas, M. C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Ghose, T (reprint author), Univ Penn, Sch Social Policy & Practice, D17 Caster Bldg,3701 Locust Walk, Philadelphia, PA 19130 USA. EM toorjo@sp2.upenn.edu OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X FU National Institutes of Health: NIAAA [U10-AA13566]; NHLBI [R01-HL095136, R01-HL090342, RCI-HL100347]; NIA [R01-AG029154, K23 AG024896] FX This work was financially supported by National Institutes of Health: NIAAA (U10-AA13566), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347), and NIA (R01-AG029154; K23 AG024896). The funding helped support the implementation of the study, i.e., the implementation of the study design, the data collection process and preparation of the data for analysis. The funders played no role in the analysis of the data, the preparation of the manuscript or decisions regarding where to submit it. NR 45 TC 3 Z9 3 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2013 VL 132 IS 1-2 BP 202 EP 206 DI 10.1016/j.drugalcdep.2013.02.004 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 216KE UT WOS:000324281400028 PM 23474200 ER PT J AU Hoef, LWV Paige, AL Riley, KO Cure, J Soltani, M Williams, FB Kennedy, RE Szaflarski, JP Knowlton, RC AF Hoef, Lawrence W. Ver Paige, A. LeBron Riley, Kristen O. Cure, Joel Soltani, Mehdi Williams, Frank B. Kennedy, Richard E. Szaflarski, Jerzy P. Knowlton, Robert C. TI Evaluating hippocampal internal architecture on MRI: Inter-rater reliability of a proposed scoring system SO EPILEPSY RESEARCH LA English DT Article DE Hippocampus; Temporal lobe epilepsy; MRI; Ammon's horn; Inter-rater reliability; Internal architecture ID SCLEROSIS; EPILEPSY; ATROPHY AB Background: Asymmetry of hippocampal internal architecture (HIA) has been reported to be a frequent imaging finding in epilepsy patients with temporal lobe epilepsy (TLE) who exhibit other signs of hippocampal sclerosis. HIA asymmetry may also be an independent predictor of the side of seizure onset in patients with otherwise normal MRI scans. The study of HIA asymmetry and its relationship to the laterality of TLE would benefit from a reliable method of assessing the clarity of HIA in MRI scans. We propose a visual scoring system that rates HIA clarity from 1 (imperceptible) to 4 (excellent) and report the inter-rater reliability (IRR) of this system. Methods: In the initial preliminary phase of this study we examined IRR using a kappa statistic (K) among a mixed group of expert and non-expert reviewers using only a brief description of the scoring system to score single images from a series of patients. In the second phase we explored the effect of training on the use of our HIA scoring system by assessing IRR among neuroimaging experts before and after a brief interactive training session. In this phase, multiple slices from each patient were scored. Separate K values and intraclass correlation coefficients (ICC) were calculated from the scores given to each hippocampal image and from the asymmetry of scores between left and right for each slice. In the third phase the effect of training on non-expert reviewers was explored using a similar approach as with the expert reviewers. Results: In the preliminary phase of the study, HIA scoring of single images showed substantial agreement among expert reviewers (kappa(HIA) = 0.65), fair agreement among non-expert reviewers (kappa(HIA) = 0.27), and a fair to moderate degree of agreement among all the reviewers as a whole (kappa(HIA) = 0.40). In the second phase, prior to training there was substantial agreement among expert reviewers in regard to the individual HIA scores (kappa(HIA) = 0.62; ICCHIA = 0.81) but only moderate agreement on the degree of asymmetry (kappa(Asym) = 0.47; ICCAsym = 0.71). Training improved agreement on the individual HIA scores (kappa(HIA) = 0.58-0.72; ICCHIA = 0.76-0.84) and on the degree of asymmetry (kappa(Asym) = 0.61-0.67; ICCAsym = 081-0.85). Among non-expert reviewers, scores improved from only a fair degree of agreement pre-training (kappa(HIA) = 0.25, kappa(Asym) = 0.25; ICCHIA = 0.68, ICCAsym = 0.66) to a moderate level of agreement after training (kappa(HIA) = 0.54, kappa(Asym) = 0.52; ICCHIA = 0.78, ICCAsym = 0.81). Conclusions: The proposed HIA scoring system has a substantial degree of inter-rater reliability among experienced neuroimaging reviewers. Training improves the detection of asymmetries in HIA score in particular. Non-expert reviewers can employ the system with a moderate degree of reliability, and training has an even greater impact on the improvement of scoring reliability. (C) 2013 Elsevier B.V. All rights reserved. C1 [Hoef, Lawrence W. Ver; Soltani, Mehdi; Szaflarski, Jerzy P.] Univ Alabama Birmingham, Dept Neurol, UAB Epilepsy Ctr, Birmingham, AL 35294 USA. [Hoef, Lawrence W. Ver; Soltani, Mehdi] Birmingham VA Med Ctr, Neurol Serv, Birmingham, AL USA. [Paige, A. LeBron; Soltani, Mehdi] Univ Iowa, Dept Neurol, Iowa Comprehens Epilepsy Program, Iowa City, IA 52242 USA. [Riley, Kristen O.; Soltani, Mehdi] Univ Alabama Birmingham, Div Neurosurg, Birmingham, AL USA. [Cure, Joel; Soltani, Mehdi] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA. [Soltani, Mehdi; Williams, Frank B.; Kennedy, Richard E.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Soltani, Mehdi; Knowlton, Robert C.] Univ Texas Houston, Texas Comprehens Epilepsy Program, Dept Neurol, Houston, TX USA. RP Hoef, LWV (reprint author), Suite 312 CIRC,1719 6th Ave South, Birmingham, AL 35205 USA. EM LVERHOEF@UAB.EDU; LeBron-Paige@uiowa.edu; KRILEY@UAB.EDU; CUREJ@UAB.EDU; soltanim_20@yahoo.com; FBW@UAB.EDU; RKennedy@ms.soph.uab.edu; SZAFLAJ@UAB.EDU; Robert.C.Knowlton@uth.tmc.edu RI Williams, Frank/H-2220-2016; OI Williams, Frank/0000-0001-7507-4870; Riley, Kristen/0000-0001-5895-6855 FU National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [1K23EB008452-01A1] FX Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number 1K23EB008452-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 18 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 2013 VL 106 IS 1-2 BP 146 EP 154 DI 10.1016/j.eplepsyres.2013.05.009 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 221NM UT WOS:000324665600016 ER PT J AU Hoef, LWV Williams, FB Kennedy, RE Szaflarski, JP Knowlton, RC AF Hoef, Lawrence W. Ver Williams, Frank B. Kennedy, Richard E. Szaflarski, Jerzy P. Knowlton, Robert C. TI Predictive value of hippocampal internal architecture asymmetry in temporal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Hippocampus; Temporal lobe epilepsy; MRI; Ammon's horn; Hippcampal internal architecture; Imaging ID HIGH-RESOLUTION MRI; SCLEROSIS; ATROPHY; SUBFIELDS; AGE AB Background: Asymmetry of hippocampal internal architecture (HIA) clarity has been suggested to be a sign of hippocampal sclerosis (HS) and is frequently associated with other MRI findings of HS. The goal of this work is to use a previously developed HIA visual scoring system (Ver Hoef et al., 2013) to quantify HIA asymmetry in a retrospective series of consecutive temporal lobe epilepsy (TLE) patients and evaluate its value in predicting laterality of seizure onset both in patients with other signs of HS (HS+) and those without (HS-). Methods: The HIA scoring system was used to rate hippocampal asymmetry and to assess the agreement between HIA and seizure lateralization. The median values of the average HIA scores for each hippocampus were compared for HS+ epileptogenic hippocampi, HS- epileptogenic hippocampi, and non-epileptogenic hippocampi with a Kruskal Wallis one-way analysis of variance by ranks. Pair-wise differences between groups were evaluated with the two-tailed Mann Whitney U test. A logistic regression model examined the utility of average HIA asymmetry score in predicting the true laterality of seizure onset as determined by video-EEG. Sensitivity and specificity are calculated using various asymmetry thresholds in each patient group. Results: Fifty-five patients were identified who met inclusion criteria. Thirteen patients (24%) were found to have hippocampal atrophy and/or signal abnormality indicative of HS (HS+) and 42 did not (HS-). Significant differences were observed in the distribution of individual and average HIA scores between each of the groups of hippocampi, with HS+ hippocampi having the lowest HIA scores and non-epileptogenic hippocampi having the highest. Logistic regression analysis showed that the average HIA asymmetry score was a strong predictor of the laterality of seizure onset (beta = 3.93508, p < 0.001). HIA asymmetry remained significant even after adjustment for HS+/HS- status (beta = 3.8854, p < 0.001). Among HS- patients, when the average HIA asymmetry score was equal to or exceeded a threshold value of 0.5, the specificity for correctly predicting the side of seizure onset was between 95% and 100% with a sensitivity of 40-45%. Among HS+ patients, a threshold of 0.3 yielded a sensitivity of 85% and specificity of 100%. Conclusions: In this report we show for the first time that HIA asymmetry is a significant predictor of the laterality of seizure onset in TLE patients with otherwise normal MRI findings, and that the proposed HIA scoring system has high specificity and moderate sensitivity for lateralizing seizure onset in patients with TLE. (C) 2013 Elsevier B.V. All rights reserved. C1 [Hoef, Lawrence W. Ver; Szaflarski, Jerzy P.] Univ Alabama Birmingham, Dept Neurol, UAB Epilepsy Ctr, Birmingham, AL 35294 USA. [Hoef, Lawrence W. Ver] Birmingham VA Med Ctr, Neurol Serv, Birmingham, AL USA. [Williams, Frank B.; Kennedy, Richard E.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Knowlton, Robert C.] Univ Texas Houston, Texas Comprehens Epilepsy Program, Dept Neurol, Houston, TX USA. RP Hoef, LWV (reprint author), Suite 312 CIRC,1719 6th Ave South, Birmingham, AL 35205 USA. EM LVERHOEF@UAB.EDU; FBW@UAB.EDU; RKennedy@ms.soph.uab.edu; SZAFLAJ@UAB.EDU; Robert.C.Knowlton@uth.tmc.edu RI Williams, Frank/H-2220-2016 OI Williams, Frank/0000-0001-7507-4870 FU National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [1K23EB008452-01A1] FX Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number 1K23EB008452-01A1. NR 19 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 2013 VL 106 IS 1-2 BP 155 EP 163 DI 10.1016/j.eplepsyres.2013.05.008 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 221NM UT WOS:000324665600017 ER PT J AU Hsieh, DT Jennesson, MM Thiele, EA AF Hsieh, David T. Jennesson, Melanie M. Thiele, Elizabeth A. TI Epileptic spasms in tuberous sclerosis complex SO EPILEPSY RESEARCH LA English DT Article DE Tuberous sclerosis complex; Infantile spasms; Epileptic spasms; Vigabatrin ID INFANTILE SPASMS; WEST-SYNDROME; RANDOMIZED-TRIAL; VIGABATRIN; CHILDREN; ENCEPHALOPATHY; EPILEPSIES; CHILDHOOD; SEIZURES; FEATURES AB Purpose: To characterize epileptic spasms (ES) occurring after the age of two years in patients with tuberous sclerosis complex (TSC), particularly treatment response to vigabatrin (VGB), which is extremely effective for infantile spasms (IS) in TSC. Methods: The authors retrospectively reviewed 19 patients with TSC and ES. Medical records were assessed for clinical and treatment data, neurocognitive, EEG, MRI data, and genetic analyses. Results: Of 391 patients with TSC, 19 (4.8%) had ES. Of those with detailed clinical data, six had infantile spasms that persisted after 2 years old, six recurred after an initial remission of infantile spasms (range 2-24 years old), and four occurred de novo over the age of two (range 2-20 years old). All concurrently had other seizure types. One had hypsarrhythmia on EEG. All had brain MRI stigmata typical of TSC. Thirteen had a mutation in TSC2, and one in TSC1. Six patients became spasm-free with medication treatment, including four with VGB, one with VGB in combination with the low glycemic index dietary treatment, and one with felbamate. Five became spasm-free after epilepsy surgery. VGB was not effective for seven patients. The majority continued to have refractory epilepsy. Conclusions: ES are not uncommon in patients with TSC, especially those with TSC2 mutations. ES in TSC occur in the setting of other seizure types and refractory epilepsy. Hypsarrhythmia is rare. VGB can be effective, but the success of VGB for ES in TSC is not equivalent to that of IS in TSC. (C) 2013 Elsevier B.V. All rights reserved. C1 [Hsieh, David T.; Jennesson, Melanie M.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM david.t.hsieh.mil@mail.mil; mjennesson-lyver@chu-reims.fr; ethiele@partners.org FU Carol and James Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01 NS024279]; "association des Amis de l'American Memorial Hospital de Reims" (France) FX This study was supported by the Carol and James Herscot Center for Tuberous Sclerosis Complex and funding by NIH/NINDS P01 NS024279. Dr. Jennesson receives financial assistance from the "association des Amis de l'American Memorial Hospital de Reims" (France). The authors confirm that they have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. We would like to thank Dr. Susana Boronat for her thoughtful review of our manuscript, and Dr. Stephen Schultz, 59th MDW Office of the Chief Scientist, U.S. Air Force, for-assistance with statistical analysis. NR 38 TC 8 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 2013 VL 106 IS 1-2 BP 200 EP 210 DI 10.1016/j.eplepsyres.2013.05.003 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 221NM UT WOS:000324665600022 PM 23796861 ER PT J AU Arkilo, D Wang, SY Thiele, EA AF Arkilo, Dimitrios Wang, Sonya Thiele, Elizabeth A. TI Time interval required for return to baseline of the background rhythm on electroencephalogram after recorded electrographic seizures SO EPILEPSY RESEARCH LA English DT Article DE Electroencephalogram; Background slowing; Electrographic seizures ID QUALITY STANDARDS SUBCOMMITTEE; AMERICAN-EPILEPSY-SOCIETY; UNPROVOKED SEIZURE; PRACTICE PARAMETER; CHILDREN; 1ST-SEIZURE; RECURRENCE; CHILDHOOD; DIAGNOSIS; NEUROLOGY AB Our objective was to assess the time interval that is required for the return to baseline of the background rhythm in the electroencephalogram (EEG) after ictal electrographic activity. We completed a retrospective EEG review of 28 adults and 13 children admitted to the epilepsy monitoring unit at Massachusetts General Hospital. EEG background rhythm on admission was considered the baseline rhythm per patient. In children the maximum time interval that was required for background rhythm to return to its baseline was 300 min, with average time of 120 min compared to a maximum of 420 min, with average time of 84 min for adults. Background slowing was shorter for frontal lobe seizures and longer for temporal lobe seizures. This study of patients with epilepsy shows that the time required for postictal slowing to resolve is short, and on average background rhythm returns to baseline within 2 h. (C) 2013 Elsevier B.V. All rights reserved. C1 [Arkilo, Dimitrios] Tufts Univ, Floating Hosp Children, Boston, MA 02111 USA. [Wang, Sonya] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92123 USA. [Thiele, Elizabeth A.] Mass Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Arkilo, D (reprint author), 225 Smith Ave N,Suite 201, St Paul, MN 55102 USA. EM darkilo@mnepilepsy.net; sonya.wang@stanfordalumni.org; ethiele@partners.org NR 11 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 2013 VL 106 IS 1-2 BP 288 EP 291 DI 10.1016/j.eplepsyres.2013.04.007 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 221NM UT WOS:000324665600034 PM 23684125 ER PT J AU Keusch, GT Rosenberg, IH Denno, DM Duggan, C Guerrant, RL Lavery, JV Tarr, PI Ward, HD Black, RE Nataro, JP Ryan, ET Bhutta, ZA Coovadia, H Lima, A Ramakrishna, B Zaidi, AKM Burgess, DCH Brewer, T AF Keusch, Gerald T. Rosenberg, Irwin H. Denno, Donna M. Duggan, Christopher Guerrant, Richard L. Lavery, James V. Tarr, Philip I. Ward, Honorine D. Black, Robert E. Nataro, James P. Ryan, Edward T. Bhutta, Zulfigar A. Coovadia, Hoosen Lima, Aldo Ramakrishna, Balakrishnan Zaidi, Anita K. M. Burgess, Deborah C. Hay Brewer, Thomas TI Implications of acquired environmental enteric dysfunction for growth and stunting in infants and children living in low- and middle-income countries SO FOOD AND NUTRITION BULLETIN LA English DT Article DE Biomarkers; infant nutrition; malabsorption; stunting ID SUBCLINICAL INTESTINAL MALABSORPTION; WORLD-HEALTH-ORGANIZATION; PEACE CORPS VOLUNTEERS; SMALL-BOWEL; TROPICAL ENTEROPATHY; NUTRITIONAL-STATUS; GAMBIAN CHILDREN; CHRONIC DIARRHEA; GIARDIA-LAMBLIA; PERMEABILITY AB Changes in small bowel function early in infancy in developing countries are increasingly being demonstrated, probably accompanied by altered mucosal architecture in most individuals, including reduced enterocyte mass and evidence of immune activation and inflammation in the mucosa. These alterations appear to be the result of factors of uncertain nature in the environment, and may be a cause of growth faltering and stunting in young children. For these reasons, this constellation of findings is being referred to as environmental enteropathy, or as we propose herein, environmental enteric dysfunction. If the causes were known and effective interventions were available, strategies and policies to intervene at-or possibly before-birth could be developed and promoted in order to prevent subsequent malnutrition and recurrent infection, which are known to interact in a cyclical and synergistic manner in a downward clinical course often ending in death. Resources would be mobilized and applied differently, and the emphasis would change from treatment to prevention. In order to move in this highly desired direction, investments in research will be required to establish the criteria to assess environmental enteric dysfunction, determine its predictive value for growth faltering and stunting, identify the causes, and propose and test potential interventions. The concepts and tools are available. What is required is the decision to move forward along this pathway to better health for infants and children in low-income countries. C1 [Keusch, Gerald T.] Boston Univ, Boston, MA 02118 USA. [Rosenberg, Irwin H.; Ward, Honorine D.] Tufts Univ, Boston, MA 02111 USA. [Denno, Donna M.] Univ Washington, Seattle, WA 98195 USA. [Duggan, Christopher] Boston Childreris Hosp, Boston, MA USA. [Guerrant, Richard L.; Nataro, James P.] Univ Virginia, Charlottesville, VA USA. [Lavery, James V.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Tarr, Philip I.] Washington Univ, St Louis, MO USA. [Black, Robert E.] Johns Hopkins Univ, Baltimore, MD USA. [Ryan, Edward T.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. [Bhutta, Zulfigar A.; Zaidi, Anita K. M.] Aga Khan Univ, Karachi, Pakistan. [Coovadia, Hoosen] Univ Witwatersrand, Johannesburg, South Africa. [Lima, Aldo] Univ Fed Ceara, Fortaleza, Ceara, Brazil. [Ramakrishna, Balakrishnan] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Burgess, Deborah C. Hay; Brewer, Thomas] Bill & Melinda Gates Fdn, Seattle, WA USA. RP Keusch, GT (reprint author), Boston Univ, Med Campus,620 Albany St, Boston, MA 02118 USA. EM keusch@bu.edu FU Bill & Melinda Gates Foundation FX The Working Group was funded by the Bill & Melinda Gates Foundation. The findings and conclusions contained in this report are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. NR 56 TC 40 Z9 41 U1 4 U2 27 PU INT NUTRITION FOUNDATION PI BOSTON PA 150 HARRISON AVE, BOSTON, MA 02111 USA SN 0379-5721 J9 FOOD NUTR BULL JI Food Nutr. Bull. PD SEP PY 2013 VL 34 IS 3 BP 357 EP 364 PG 8 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 220QD UT WOS:000324601100008 PM 24167916 ER PT J AU Nallamshetty, S Chan, SY Loscalzo, J AF Nallamshetty, Shriram Chan, Stephen Y. Loscalzo, Joseph TI Hypoxia: A master regulator of microRNA biogenesis and activity SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE Hypoxia; MicroRNA; Hypoxamir; HIF; Free radicals ID INDUCIBLE FACTOR 1-ALPHA; NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITION; ENDOPLASMIC-RETICULUM STRESS; HIF-1-DEPENDENT REPRESSION; MICROPROCESSOR COMPLEX; PULMONARY-HYPERTENSION; TRANSCRIPTION FACTORS; ISCHEMIA-REPERFUSION; CELL-PROLIFERATION AB Hypoxia, or low oxygen tension, is a unique environmental stress that induces global changes in a complex regulatory network of transcription factors and signaling proteins to coordinate cellular adaptations in metabolism, proliferation, DNA repair, and apoptosis. Several lines of evidence now establish microRNAs (miRNAs), which are short noncoding RNAs that regulate gene expression through posttranscriptional mechanisms, as key elements in this response to hypoxia. Oxygen deprivation induces a distinct shift in the expression of a specific group of miRNAs, termed hypoxamirs, and emerging evidence indicates that hypoxia regulates several facets of hypoxamir transcription, maturation, and function. Transcription factors such as hypoxia-inducible factor are upregulated under conditions of low oxygen availability and directly activate the transcription of a subset of hypoxamirs. Conversely, hypoxia selectively represses other hypoxamirs through less well characterized mechanisms. In addition, oxygen deprivation has been directly implicated in epigenetic modifications such as DNA demethylation that control specific miRNA transcription. Finally, hypoxia also modulates the activity of key proteins that control posttranscriptional events in the maturation and activity of miRNAs. Collectively, these findings establish hypoxia as an important proximal regulator of miRNA biogenesis and function. It will be important for future studies to address the relative contributions of transcriptional and posttranscriptional events in the regulation of specific hypoxamirs and how such miRNAs are coordinated in order to integrate into the complex hierarchical regulatory network induced by hypoxia. (c) 2013 Elsevier Inc. All rights reserved. C1 [Nallamshetty, Shriram; Chan, Stephen Y.; Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Nallamshetty, Shriram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. RP Loscalzo, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. EM jloscalzo@partners.org FU NIH [5T32HL007208-34, HL096843, HL061795, HL48743, HL107192, HL70819, HL108630]; McArthur-Radovsky Fund; Lerner Fund; Harris Fund; Watkins Fund; Gilead Research Scholars Fund; Pulmonary Hypertension Association FX We thank S. Tribuna for expert administrative assistance. This work was supported by NIH Training Grant 5T32HL007208-34 (S.N.); NIH Grant HL096843, the McArthur-Radovsky, Lerner, Harris, and Watkins Funds, the Gilead Research Scholars Fund, and the Pulmonary Hypertension Association (S.Y.C.); and NIH Grants HL061795, HL48743, HL107192, HL70819, and HL108630 (J.L.). The funding sources for S.N., S.Y.C., and J.L. did not participate in the preparation of this report or the decision to submit it for publication. NR 123 TC 62 Z9 66 U1 2 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 2013 VL 64 SI SI BP 20 EP 30 DI 10.1016/j.freeradbiomed.2013.05.022 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 217JN UT WOS:000324355900004 PM 23712003 ER PT J AU Andrews, LK Coviello, J Hurley, E Rose, L Redeker, NS AF Andrews, Laura Kierol Coviello, Jessica Hurley, Elisabeth Rose, Leonie Redeker, Nancy S. TI "I'd eat a bucket of nails if you told me it would help me sleep:" Perceptions of insomnia and its treatment in patients with stable heart failure SO HEART & LUNG LA English DT Article DE Insomnia; Heart failure; Sleep; Cognitive behavioral therapy for insomnia; Hypnotics ID COGNITIVE-BEHAVIORAL THERAPY; QUALITY-OF-LIFE; DAYTIME FUNCTION; SCALE; POPULATION; VALIDATION; SYMPTOMS; NOCTURIA; PEOPLE; INDEX AB Background: Poor sleep, including insomnia, is common among patients with heart failure (HF). However, little is known about the efficacy of interventions for insomnia in this population. Prior to developing interventions, there is a need for better understanding of patient perceptions about insomnia and its treatment. Objeetives: To evaluate HF patients' perceptions about 1) insomnia and its consequences; 2) predisposing, precipitating, and perpetuating factors for insomnia; 3) self-management strategies and treatments for insomnia; and 4) preferences for insomnia treatment. Methods: The study, guided by the "3 P" model of insomnia, employed a parallel convergent mixed methods design in which we obtained qualitative data through focus groups and quantitative data through questionnaires (sleep quality, insomnia severity, dysfunctional beliefs and attitudes about sleep; sleep-related daytime symptoms and functional performance). Content analysis was used to evaluate themes arising from the focus group data, and descriptive statistics were used to analyze the quantitative data. The results of both forms of data collection were compared and synthesized. Results: HF patients perceived insomnia as having a negative impact on daytime function and comorbid health problems, pain, nocturia, and psychological factors as perpetuating factors. They viewed use of hypnotic medications as often necessary but disliked negative daytime side effects. They used a variety of strategies to manage their insomnia, but generally did not mention their sleep concerns to physicians whom they perceived as not interested in sleep. Conclusions: HF patients believe insomnia is important and multi-factorial. Behavioral treatments, such as cognitive behavioral therapy, for insomnia may be efficacious in modifying perpetuating factors and likely to be acceptable to patients. (C) 2013 Elsevier Inc. All rights reserved. C1 [Andrews, Laura Kierol; Coviello, Jessica; Rose, Leonie; Redeker, Nancy S.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Hurley, Elisabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Andrews, LK (reprint author), Yale Univ, Sch Nursing, 100 Church St South, New Haven, CT 06536 USA. EM laura.andrews@yale.edu RI Redeker, Nancy/Q-8252-2016 OI Redeker, Nancy/0000-0001-7817-2708 FU Yale School of Nursing Center for Self and Family Management in Vulnerable Populations [P30NR08999] FX This study was funded by the Yale School of Nursing Center for Self and Family Management in Vulnerable Populations (grant #: P30NR08999). NR 51 TC 7 Z9 7 U1 2 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD SEP-OCT PY 2013 VL 42 IS 5 BP 339 EP 345 DI 10.1016/j.hrtlng.2013.05.003 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 219MO UT WOS:000324511300006 PM 23998381 ER PT J AU Liu, YT Hauser, MA Akafo, SK Qin, XJ Miura, S Gibson, JR Wheeler, J Gaasterland, DE Challa, P Herndon, LW Ritch, R Moroi, SE Pasquale, LR Girkin, CA Budenz, DL Wiggs, JL Richards, JE Ashley-Koch, AE Allingham, RR AF Liu, Yutao Hauser, Michael A. Akafo, Stephen K. Qin, Xuejun Miura, Shiroh Gibson, Jason R. Wheeler, Joshua Gaasterland, Douglas E. Challa, Pratap Herndon, Leon W. Ritch, Robert Moroi, Sayoko E. Pasquale, Louis R. Girkin, Christopher A. Budenz, Donald L. Wiggs, Janey L. Richards, Julia E. Ashley-Koch, Allison E. Allingham, R. Rand CA Int Consortium African Ancestry RE TI Investigation of Known Genetic Risk Factors for Primary Open Angle Glaucoma in Two Populations of African Ancestry SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE association; genetics; POAG; African; African American ID GENOME-WIDE ASSOCIATION; TEMA-EYE-SURVEY; TO-DISC RATIO; MYOCILIN MUTATIONS; SUSCEPTIBILITY LOCI; VISUAL IMPAIRMENT; COMMON VARIANTS; UNITED-STATES; WEST-AFRICA; PREVALENCE AB PURPOSE. Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. METHODS. We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP <= 21 mm Hg) and high pressure glaucoma (HPG, IOP > 21 mm Hg). RESULTS. In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. CONCLUSIONS. POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population. C1 [Liu, Yutao; Hauser, Michael A.; Qin, Xuejun; Miura, Shiroh; Gibson, Jason R.; Wheeler, Joshua; Ashley-Koch, Allison E.] Duke Univ, Dept Med, Med Ctr, Durham, NC 27710 USA. [Liu, Yutao; Hauser, Michael A.; Challa, Pratap; Herndon, Leon W.; Allingham, R. Rand] Duke Univ, Dept Ophthalmol, Med Ctr, Durham, NC 27710 USA. [Akafo, Stephen K.] Univ Ghana, Unit Ophthalmol, Dept Surg, Sch Med, Accra, Ghana. [Gaasterland, Douglas E.] Eye Doctors Washington DC, Washington, DC USA. [Ritch, Robert] New York Eye & Ear Infirm, Dept Ophthalmol, Einhorn Clin Res Ctr, New York, NY 10003 USA. [Moroi, Sayoko E.; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Girkin, Christopher A.] Univ Alabama Birmingham, Dept Ophthalmol, Birmingham, AL 35294 USA. [Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. [Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Allingham, RR (reprint author), Duke Univ, Ctr Eye, Box 3802, Durham, NC 27710 USA. EM allin002@mc.duke.edu OI Girkin, Chris/0000-0002-9676-4499; Ashley-Koch, Allison/0000-0001-5409-9155 FU National Eye Institute [R01EY013315, R01EY019126, P30EY005722, R03EY014939, R01EY015543, R01EY011671, R01EY09580, R01EY015872]; Research to Prevent Blindness FX Supported by National Eye Institute Grants R01EY013315 (MAH), R01EY019126 (MAH), P30EY005722 (MAH), R03EY014939 (RRA), R01EY015543 (RRA), R01EY011671 (JER), R01EY09580 (JER), and R01EY015872 (JLW); and Research to Prevent Blindness (YL, JER, LRP). NR 53 TC 23 Z9 23 U1 1 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2013 VL 54 IS 9 BP 6248 EP 6254 DI 10.1167/iovs.13-12779 PG 7 WC Ophthalmology SC Ophthalmology GA 228EV UT WOS:000325169500040 PM 23963167 ER PT J AU Neilan, TG Coelho, OR Danik, SB Shah, RV Dodson, JA Verdini, DJ Tokuda, M Daly, CA Tedrow, UB Stevenson, WG Jerosch-Herold, M Ghoshhajra, BB Kwong, RY AF Neilan, Tomas G. Coelho-Filho, Otavio R. Danik, Stephan B. Shah, Ravi V. Dodson, John A. Verdini, Daniel J. Tokuda, Michifumi Daly, Caroline A. Tedrow, Usha B. Stevenson, William G. Jerosch-Herold, Michael Ghoshhajra, Brian B. Kwong, Raymond Y. TI CMR Quantification of Myocardial Scar Provides Additive Prognostic Information in Nonischemic Cardiomyopathy SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac magnetic resonance; implantable cardioverter-defibrillators; late gadolinium enhancement; nonischemic cardiomyopathy ID CARDIOVASCULAR MAGNETIC-RESONANCE; SUDDEN CARDIAC DEATH; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; RANDOMIZED-CONTROLLED-TRIALS; ADVANCED HEART-FAILURE; DILATED CARDIOMYOPATHY; PRIMARY PREVENTION; FIBROSIS; ASSOCIATION; CARDIOLOGY AB OBJECTIVES This study sought to determine whether the extent of late gadolinium enhancement (LGE) can provide additive prognostic information in patients with a nonischemic dilated cardiomyopathy (NIDC) with an indication for implantable cardioverter-defibrillator (ICD) therapy for the primary prevention of sudden cardiac death (SCD). BACKGROUND Data suggest that the presence of LGE is a strong discriminator of events in patients with NIDC. Limited data exist on the role of LGE quantification. METHODS The extent of LGE and clinical follow-up were assessed in 162 patients with NIDC prior to ICD insertion for primary prevention of SCD. LGE extent was quantified using both the standard deviation-based (2-SD) method and the full-width half-maximum (FWHM) method. RESULTS We studied 162 patients with NIDC (65% male; mean age: 55 years; left ventricular ejection fraction [LVEF]: 26 +/- 8%) and followed up for major adverse cardiac events (MACE), including cardiovascular death and appropriate ICD therapy, for a mean of 29 +/- 18 months. Annual MACE rates were substantially higher in patients with LGE (24%) than in those without LGE (2%). By univariate association, the presence and the extent of LGE demonstrated the strongest associations with MACE (LGE presence, hazard ratio [HR]: 14.5 [95% confidence interval (CI): 6.1 to 32.6; p < 0.001]; LGE extent, HR: 1.15 per 1% increase in volume of LGE [95% CI: 1.12 to 1.18; p < 0.0001]). Multivariate analyses showed that LGE extent was the strongest predictor in the best overall model for MACE, and a 7-fold hazard was observed per 10% LGE extent after adjustments for patient age, sex, and LVEF (adjusted HR: 7.61; p < 0.0001). LGE quantitation by 2-SD and FWHM both demonstrated robust prognostic association, with the highest MACE rate observed in patients with LGE involving >6.1% of LV myocardium. CONCLUSIONS LGE extent may provide further risk stratification in patients with NIDC with a current indication for ICD implantation for the primary prevention of SCD. Strategic guidance on ICD therapy by cardiac magnetic resonance in patients with NIDC warrants further study. (c) 2013 by the American College of Cardiology Foundation C1 [Neilan, Tomas G.; Coelho-Filho, Otavio R.; Shah, Ravi V.; Dodson, John A.; Tokuda, Michifumi; Daly, Caroline A.; Tedrow, Usha B.; Stevenson, William G.; Jerosch-Herold, Michael; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med & Radiol, Div Cardiovasc, Noninvas Cardiovasc Imaging Sect, Boston, MA 02115 USA. [Neilan, Tomas G.; Danik, Stephan B.; Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Neilan, Tomas G.; Verdini, Daniel J.; Ghoshhajra, Brian B.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Neilan, Tomas G.; Verdini, Daniel J.; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kwong, RY (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM rykwong@partners.org FU American Heart Association [12FTF12060588]; National Institutes of Health [T32 HL094301-02, R01HL090634-01A1, R01HL091157] FX From the *Non-invasive Cardiovascular Imaging Section, Cardiovascular Division, Department of Medicine and Radiology, Brigham and Women's Hospital, Boston, Massachusetts; dagger Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; and the double dagger Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. This work was supported by an American Heart Association Fellow to Faculty Grant (12FTF12060588, to Dr. Neilan), a National Institutes of Health T32 Training Grant (T32 HL094301-02, to Dr. Neilan), and National Institutes of Health research grants (R01HL090634-01A1, MJH; R01HL091157, to Dr. Kwong). All authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 31 TC 38 Z9 39 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2013 VL 6 IS 9 BP 944 EP 954 DI 10.1016/j.jcmg.2013.05.013 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 222FN UT WOS:000324716000003 PM 23932642 ER PT J AU La Gerche, A Baggish, AL Knuuti, J Prior, DL Sharma, S Heidbuchel, H Thompson, PD AF La Gerche, Andre Baggish, Aaron L. Knuuti, Juhani Prior, David L. Sharma, Sanjay Heidbuchel, Hein Thompson, Paul D. TI Cardiac Imaging and Stress Testing Asymptomatic Athletes to Identify Those at Risk of Sudden Cardiac Death SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE athlete's heart; cardiomyopathy; cardiovascular screening; exercise; risk prediction; sudden cardiac death ID CORONARY-ARTERY-DISEASE; DISTINGUISHING HYPERTROPHIC CARDIOMYOPATHY; CARDIOVASCULAR MAGNETIC-RESONANCE; AMERICAN-HEART-ASSOCIATION; FOLLOW-UP; VENTRICULAR DYSFUNCTION; MYOCARDIAL FIBROSIS; GENERAL-POPULATION; YOUNG-ADULTS; TASK-FORCE AB Sudden cardiac death in young athletes is rare but tragic. The cardiology community is faced with the challenge of providing a sensible strategy for the prevention of SCD while simultaneously reaffirming that the benefits of regular exercise far outweigh potential risks. At present, there is a broad range of screening recommendations dependent upon country, sporting discipline, and competition level. While much recent debate has focused on the efficacy of screening with electrocardiography, a number of sporting bodies also mandate the inclusion of exercise testing and echocardiography in screening protocols. Cardiac magnetic resonance imaging, coronary calcium scoring and computed tomography coronary angiography have also been promoted as potentially valuable screening tools for competitive athletes. This review will examine the controversial topic of utilizing cardiac imaging for athlete pre-participation screening. Specifically, the limitations of screening for relatively rare disorders using imaging tools with uncertain or imperfect accuracy will be addressed. Current evidence suggests that the accuracy of all cardiac imaging modalities is insufficient to justify their use as primary screening modalities in athletes. Atypical findings such as marked cardiac dilation, reduced deformation, or small patches of delayed gadolinium enhancement may be commonly encountered in well-trained athletes, but, at present, the prognostic significance of such findings is unknown. Resulting uncertainty for the clinician and athlete has the potential for psychological stress, further testing, and unnecessary exclusions from competition. However, these concerns must not be confused with the extremely useful applications of cardiac imaging for the assessment of athletes with symptoms, an abnormal electrocardiogram or a positive family history. As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes. (c) 2013 by the American College of Cardiology Foundation C1 [La Gerche, Andre; Prior, David L.] Univ Melbourne, St Vincents Dept Med, Melbourne, Vic, Australia. [La Gerche, Andre; Heidbuchel, Hein] Univ Hosp Leuven, Dept Cardiovasc Med, Louvain, Belgium. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Knuuti, Juhani] Univ Turku, Turku PET Ctr, Turku, Finland. [Knuuti, Juhani] Turku Univ Hosp, FIN-20520 Turku, Finland. [Sharma, Sanjay] Univ London, Dept Cardiovasc Sci, London, England. [Thompson, Paul D.] Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. RP La Gerche, A (reprint author), St Vincents Hosp, Dept Cardiol, POB 2900, Fitzroy, Vic 3065, Australia. EM Andre.LaGerche@svhm.org.au OI Knuuti, Juhani/0000-0003-3156-9593 FU Boehringer-Ingelheim; Daiichi Sankyo; Bayer; Pfizer; Sanofi-Aventis; Medtronic; Biotronik; Merck; Boston Scientific; St. Jude Medical; AstraZeneca; Siemens FX From the *St Vincent's Department of Medicine, University of Melbourne, Melbourne, Australia; dagger Department of Cardiovascular Medicine, University Hospital Leuven, Leuven, Belgium; double dagger Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; parallel to Department of Cardiovascular Sciences, St George's, University of London, London, United Kingdom; and the Division of Cardiology, Hartford Hospital, Hartford, Connecticut. Dr. Heidbuchel has received speakers' fees from Boehringer-Ingelheim, Daiichi Sankyo, Bayer, Pfizer, Sanofi-Aventis, Medtronic, Biotronik, and Merck; unconditional research grants from Medtronic, Biotronik, Boston Scientific, St. Jude Medical, and AstraZeneca; and collaborative research support from Siemens. Dr. Thompson owns stock in General Electric. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 80 TC 25 Z9 25 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2013 VL 6 IS 9 BP 993 EP 1007 DI 10.1016/j.jcmg.2013.06.003 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 222FN UT WOS:000324716000009 PM 24029371 ER PT J AU Ando, T Sato, S Kobayashi, H Nawashiro, H Ashida, H Hamblin, MR Obara, M AF Ando, Takahiro Sato, Shunichi Kobayashi, Hiroaki Nawashiro, Hiroshi Ashida, Hiroshi Hamblin, Michael R. Obara, Minoru TI Low-level laser therapy for spinal cord injury in rats: effects of polarization SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE low-level laser therapy; photobiomodulation; polarization; spinal cord injury; functional evaluation ID BIPHASIC DOSE-RESPONSE; FUNCTIONAL RECOVERY; LIGHT-PROPAGATION; NEUROLOGICAL DEFICITS; STEM-CELLS; IRRADIATION; REGENERATION; TRANSECTION; COMBINATION; MECHANISMS AB The effects of laser polarization on the efficacy of near-infrared low-level laser therapy for spinal cord injury (SCI) are presented. Rat spinal cords were injured with a weight-drop device, and the lesion sites were directly irradiated with a linearly polarized 808-nm diode laser positioned either perpendicular or parallel to the spine immediately after the injury and daily for five consecutive days. Functional recovery was assessed daily by an open-field test. Regardless of the polarization direction, functional scores of SCI rats that were treated with the 808-nm laser irradiation were significantly higher than those of SCI alone group (Group 1) from day 5 after injury. The locomotive function of SCI rats irradiated parallel to the spinal column (Group 3) was significantly improved from day 10 after injury, compared to SCI rats treated with the linear polarization perpendicular to the spinal column (Group 2). There were no significant differences in ATP contents in the injured tissue among the three groups. We speculate that the higher efficacy with parallel irradiation is attributable to the deeper light penetration into tissue with anisotropic scattering. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Ando, Takahiro; Obara, Minoru] Keio Univ, Dept Elect & Elect Engn, Kohoku Ku, Yokohama, Kanagawa 2238522, Japan. [Sato, Shunichi; Ashida, Hiroshi] Natl Def Med Coll, Res Inst, Div Biomed Informat Sci, Tokorozawa, Saitama 3598513, Japan. [Kobayashi, Hiroaki; Nawashiro, Hiroshi] Natl Def Med Coll, Dept Neurosurg, Tokorozawa, Saitama 3598513, Japan. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Massachusetts Inst Technol MIT Div Hlth S, Cambridge, MA 02139 USA. RP Sato, S (reprint author), Natl Def Med Coll, Res Inst, Div Biomed Informat Sci, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan. EM shunsato@ndmc.ac.jp OI Hamblin, Michael/0000-0001-6431-4605 FU National Defense Medical College; US NIH [R01AI050875] FX This work was supported in part by the Special Research Program of the National Defense Medical College. T. Ando is grateful for the JSPS Research Fellows for Young Scientists. M. R. Hamblin was supported by US NIH R01AI050875. NR 45 TC 5 Z9 5 U1 0 U2 8 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP PY 2013 VL 18 IS 9 AR 098002 DI 10.1117/1.JBO.18.9.098002 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 222QX UT WOS:000324747300025 PM 24030687 ER PT J AU Ponticorvo, A Cardenas, D Dunn, AK Ts'o, D Duong, TQ AF Ponticorvo, Adrien Cardenas, Damon Dunn, Andrew K. Ts'o, Daniel Duong, Timothy Q. TI Laser speckle contrast imaging of blood flow in rat retinas using an endoscope SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE laser speckle imaging; retinal imaging; gas challenge; flicker stimulation ID OPTIC-NERVE; PHOTOGRAPHY; RESOLUTION; IMAGES; FUNDUS AB Laser speckle contrast imaging (LSCI) offers a cost-effective means to image blood flow in vivo. However, it is not commonly used to image rodent retinas because of the challenges associated with imaging through the curved cornea and delivering light through the highly scattering lens. A solution to overcome these problems by using LSCI in conjunction with an endoscope to obtain high spatiotemporal blood flow images is described. Its utility is demonstrated by imaging blood flow changes in rat retinas using hyperoxic, hypercapnic, and visual (flicker) stimulations. Hypercapnia increases blood flow, hyperoxia decreases blood flow, and visual stimulation increases blood flow in the retina relative to basal conditions. The time-to-peak of the LSCI response to visual stimulation is also measured. This approach may prove useful to investigate dysregulation in blood flow-evoked responses in retinal diseases and to evaluate treatment strategies in rodents. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Ponticorvo, Adrien; Cardenas, Damon; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Dunn, Andrew K.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Ts'o, Daniel] SUNY Upstate Med Univ, Dept Neurosurg & Neurosci, Syracuse, NY 13210 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Dunn, Andrew/I-9527-2014 FU Department of Veterans Affairs (VA MERIT Award); NIH [R01 EY018855, R01 EY014211] FX This work was supported in part by the Department of Veterans Affairs (VA MERIT Award) and NIH (R01 EY018855 and R01 EY014211). NR 22 TC 8 Z9 8 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP PY 2013 VL 18 IS 9 AR 090501 DI 10.1117/1.JBO.18.9.090501 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 222QX UT WOS:000324747300001 PM 24064947 ER PT J AU Herter-Sprie, GS Kung, AL Wong, KK AF Herter-Sprie, Grit S. Kung, Andrew L. Wong, Kwok-Kin TI New cast for a new era: preclinical cancer drug development revisited SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID CELL LUNG-CANCER; ENGINEERED MOUSE MODELS; ORTHOTOPIC IMPLANTATION; PANCREATIC-CANCER; TUMOR XENOGRAFTS; BREAST-CANCER; NUDE-MICE; IN-VITRO; SPONTANEOUS METASTASIS; TELOMERE DYSFUNCTION AB Molecularly targeted agents promise to revolutionize therapeutics by reducing morbidity and mortality in patients with cancer. However, despite an urgent need for more effective anticancer compounds, current preclinical drug evaluations largely fail to satisfy the demand. New preclinical strategies, including the improvement of sophisticated mouse models and co-clinical study designs, are being used to augment the predictive value of animal-based translational cancer research. Here, we review the development of successful preclinical antineoplastic agents, their associated limitations, and alternative methods to predict clinical outcomes. C1 [Herter-Sprie, Grit S.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Herter-Sprie, Grit S.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Herter-Sprie, Grit S.; Wong, Kwok-Kin] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Herter-Sprie, Grit S.; Wong, Kwok-Kin] Dana Farber Canc Inst, Ludwig Ctr, Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. [Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Belfer Inst Appl Canc Sci, 450 Brookline Ave,HIM 243, Boston, MA 02215 USA. EM kwong1@partners.org OI Kung, Andrew/0000-0002-9091-488X; wong, kwok kin/0000-0001-6323-235X FU Deutsche Forschungsgemeinschaft [HE 6897/1-1]; National Cancer Institute [CA122794, CA166480, CA163896, P01CA154303, R01CA140594, U01CA141576]; Susan Spooner Research Fund; National Institutes of Health FX We apologize to our colleagues for the omission of references to many important contributions due to space limitations. We thank members of the Wong and Kung laboratories for helpful discussions. This work was supported by the Deutsche Forschungsgemeinschaft (HE 6897/1-1 to G.S. Herter-Sprie), the National Cancer Institute (CA122794, CA166480, CA163896, P01CA154303, R01CA140594, U01CA141576 to K-K. Wong), the Susan Spooner Research Fund (to K.-K. Wong), and the National Institutes of Health (to A.L. Kung). NR 81 TC 22 Z9 22 U1 3 U2 19 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2013 VL 123 IS 9 BP 3639 EP 3645 DI 10.1172/JCI68340 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 220DQ UT WOS:000324562600002 PM 23999436 ER PT J AU Vander Heiden, MG AF Vander Heiden, Matthew G. TI Exploiting tumor metabolism: challenges for clinical translation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID NONSMALL CELL LUNG; CANCER METABOLISM; GLUTAMINE-METABOLISM; AEROBIC GLYCOLYSIS; TRANSFORMED-CELLS; C-MYC; GROWTH; PET; PROLIFERATION; CARBOXYLATION AB The metabolism of cancer cells differs from most normal cells, but how to exploit this difference for patient benefit is incompletely understood. Cancer cells require altered metabolism to efficiently incorporate nutrients into biomass and support abnormal proliferation. In addition, the survival of tumor cells outside of a normal tissue context requires adaptation of metabolism to different microenvironrnents. Some existing chemotherapies target metabolic enzymes, and there is a resurgent interest in developing new cancer drugs that interfere with metabolism. Success with this approach depends on understanding why specific metabolic pathways are important for cancer cells, determining how best to select patients, and developing technologies for monitoring patient response to therapies that target metabolic enzymes. The articles in this Review series address these issues, with a focus on how altered metabolism might influence tumor progression and how this knowledge might inform the use of new therapies targeting cancer metabolism. Emerging biomarker strategies to guide drug development are also highlighted. C1 [Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Dept Biol, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst, 77 Massachusetts Ave,76-561, Cambridge, MA 02139 USA. EM mvh@mit.edu FU Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; Smith Family; Stern Family; Lustgarten Foundation; NIH FX I thank members of the Vander Heiden laboratory for thoughtful comments on the manuscript and acknowledge support from the Burroughs Wellcome Fund, the Damon Runyon Cancer Research Foundation, the Smith Family, the Stern Family, the Lustgarten Foundation, and the NIH. NR 59 TC 26 Z9 27 U1 1 U2 27 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2013 VL 123 IS 9 BP 3648 EP 3651 DI 10.1172/JCI72391 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 220DQ UT WOS:000324562600003 PM 23999437 ER PT J AU Andronesi, OC Rapalino, O Gerstner, E Chi, A Batchelor, TT Cahil, DP Sorensen, AG Rosen, BR AF Andronesi, Ovidiu C. Rapalino, Otto Gerstner, Elizabeth Chi, Andrew Batchelor, Tracy T. Cahil, Dan P. Sorensen, A. Gregory Rosen, Bruce R. TI Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID CORRELATED MR SPECTROSCOPY; ACUTE MYELOID-LEUKEMIA; IN-VIVO; ONCOMETABOLITE 2-HYDROXYGLUTARATE; GLIOMA PATIENTS; BRAIN-TUMORS; METABOLIC PROFILES; QUANTUM FILTER; NMR; SUFFICIENT AB The investigation of metabolic pathways disturbed in isocitrate dehydrogenase (IDH) mutant tumors revealed that the hallmark metabolic alteration is the production of D-2-hydroxyglutarate (D-2HG). The biological impact of D-2HG strongly suggests that high levels of this metabolite may play a central role in propagating downstream the effects of mutant IDH, leading to malignant transformation of cells. Hence, D-2HG may be an ideal biomarker for both diagnosing and monitoring treatment response targeting IDH mutations. Magnetic resonance spectroscopy (MRS) is well suited to the task of noninvasive D-2HG detection, and there has been much interest in developing such methods. Here, we review recent efforts to translate methodology using MRS to reliably measure in vivo D-2HG into clinical research. C1 [Andronesi, Ovidiu C.; Rosen, Bruce R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Rapalino, Otto] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gerstner, Elizabeth; Chi, Andrew; Batchelor, Tracy T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gerstner, Elizabeth; Chi, Andrew; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurooncol, Boston, MA USA. [Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Cahil, Dan P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Sorensen, A. Gregory] Siemens Healthcare USA, Malvern, PA USA. RP Andronesi, OC (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 13th St,Bldg 149,Suite 2301, Boston, MA 02114 USA. EM ovidiu@nmr.mgh.harvard.edu OI Cahill, Daniel/0000-0003-2552-6546 FU KL2 Medical Research Investigator Training (MeRIT) award from Harvard Catalyst; Harvard Clinical and Translational Science Center [KL2 RR 025757]; NIH [K24CA125440A, R01CA129371]; Martinos Center for Biomedical Imaging [S10RR013026, S10RR021110, S10RR023401] FX The MRS of IDH glioma patients was initiated by A.G. Sorensen while he was employed at Massachusetts General Hospital; A.G. Sorensen is currently employed by Siemens Healthcare USA. Discussions with Matthew G. vander Heiden were extremely valuable throughout the course of the study. O.C. Andronesi was supported by a KL2 Medical Research Investigator Training (MeRIT) award from Harvard Catalyst and by The Harvard Clinical and Translational Science Center (grant KL2 RR 025757). Additional funding was provided by the NIH for T.T. Batchelor (grants K24CA125440A and R01CA129371) and by shared instrumentation grants (S10RR013026, S10RR021110, and S10RR023401 from Martinos Center for Biomedical Imaging). NR 61 TC 38 Z9 39 U1 4 U2 19 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2013 VL 123 IS 9 BP 3659 EP 3663 DI 10.1172/JCI67229 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 220DQ UT WOS:000324562600005 PM 23999439 ER PT J AU Burkhardt, UE Hainz, U Stevenson, K Goldstein, NR Pasek, M Naito, M Wu, D Ho, VT Alonso, A Hammond, NN Wong, J Sievers, QL Brusic, A McDonough, SM Zeng, WY Perrin, A Brown, JR Canning, CM Koreth, J Cutler, C Armand, P Neuberg, D Lee, JS Antin, JH Mulligan, RC Sasada, T Ritz, J Soiffer, RJ Dranoff, G Alyea, EP Wu, CJ AF Burkhardt, Ute E. Hainz, Ursula Stevenson, Kristen Goldstein, Natalie R. Pasek, Mildred Naito, Masayasu Wu, Di Ho, Vincent T. Alonso, Anselmo Hammond, Naa Norkor Wong, Jessica Sievers, Quinlan L. Brusic, Ana McDonough, Sean M. Zeng, Wanyong Perrin, Ann Brown, Jennifer R. Canning, Christine M. Koreth, John Cutler, Corey Armand, Philippe Neuberg, Donna Lee, Jeng-Shin Antin, Joseph H. Mulligan, Richard C. Sasada, Tetsuro Ritz, Jerome Soiffer, Robert J. Dranoff, Glenn Alyea, Edwin P. Wu, Catherine J. TI Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; MYELOID SUPPRESSOR-CELLS; TERM-FOLLOW-UP; ANTITUMOR IMMUNITY; TUMOR-IMMUNITY; B-CELL; GM-CSF; DENDRITIC CELLS AB Background. Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. Methods. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. Results. At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8(+) T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-gamma, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8(+) T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Conclusion. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. C1 [Burkhardt, Ute E.; Hainz, Ursula; Naito, Masayasu; Wu, Di; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L.; Brusic, Ana; Zeng, Wanyong; Canning, Christine M.; Sasada, Tetsuro; Ritz, Jerome; Dranoff, Glenn; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Burkhardt, Ute E.; Hainz, Ursula; Goldstein, Natalie R.; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T.; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L.; Brusic, Ana; McDonough, Sean M.; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R.; Canning, Christine M.; Koreth, John; Cutler, Corey; Armand, Philippe; Antin, Joseph H.; Ritz, Jerome; Soiffer, Robert J.; Dranoff, Glenn; Alyea, Edwin P.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stevenson, Kristen; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brown, Jennifer R.; Canning, Christine M.; Koreth, John; Cutler, Corey; Armand, Philippe; Antin, Joseph H.; Ritz, Jerome; Soiffer, Robert J.; Dranoff, Glenn; Alyea, Edwin P.; Wu, Catherine J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Lee, Jeng-Shin; Mulligan, Richard C.] Harvard Univ, Sch Med, Dept Genet, Harvard Gene Therapy Initiat, Boston, MA USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Room 420,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU National Cancer Institute [5R21CA115043-2]; National Heart, Lung, and Blood Institute [5R01HL103532-03]; Claudia Adams Barr Program in Cancer Research; Leukemia and Lymphoma Translational Research Program; Early Career Physician-Scientist Award of the Howard Hughes Medical Institute; Damon-Runyon Cancer Research Foundation [CI-38-07]; [230 AR42689] FX We thank the Dana-Farber Cancer Institute (DFCI) clinical transplant team for their expert clinical care, and the staff of the DFCI Cell Manipulation Core Facility and Pasquarello Tissue Bank for their assistance. We also thank James Rheinwald and Patricia Barron of the Cell Culture Core of the Harvard Skin Disease Research Center (grant 230 AR42689) for initiating the primary human dermal fibroblast cell lines used in this project, and Wandi Zhang and Jaclyn Grundy for their excellent technical assistance. C.J. Wu acknowledges support from the National Cancer Institute (5R21CA115043-2), the National Heart, Lung, and Blood Institute (5R01HL103532-03), the Claudia Adams Barr Program in Cancer Research, the Leukemia and Lymphoma Translational Research Program, and the Early Career Physician-Scientist Award of the Howard Hughes Medical Institute. C.J. Wu is a Damon-Runyon Clinical Investigator supported in part by the Damon-Runyon Cancer Research Foundation (CI-38-07). NR 43 TC 32 Z9 32 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2013 VL 123 IS 9 BP 3756 EP 3765 DI 10.1172/JCI69008 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 220DQ UT WOS:000324562600021 PM 23912587 ER PT J AU Shim, JH Greenblatt, MB Zou, WG Huang, ZW Wein, MN Brady, N Hu, D Charron, J Brodkin, HR Petsko, GA Zaller, D Zhai, B Gygi, S Glimcher, LH Jones, DC AF Shim, Jae-Hyuck Greenblatt, Matthew B. Zou, Weiguo Huang, Zhiwei Wein, Marc N. Brady, Nicholas Hu, Dorothy Charron, Jean Brodkin, Heather R. Petsko, Gregory A. Zaller, Dennis Zhai, Bo Gygi, Steven Glimcher, Laurie H. Jones, Dallas C. TI Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID WNT/BETA-CATENIN; SKELETAL DEVELOPMENT; KINASE ACTIVATION; BETA-CATENIN; MAP KINASES; DIFFERENTIATION; GROWTH; MICE; SUBSTRATE; MOTIF AB Mice deficient in Schnurri-3 (SHN3; also known as HIVEP3) display increased bone formation, but harnessing this observation for therapeutic benefit requires an improved understanding of how SHN3 functions in osteoblasts. Here we identified SHN3 as a dampener of ERK activity that functions in part downstream of WNT signaling in osteoblasts. A D-domain motif within SHN3 mediated the interaction with and inhibition of ERK activity and osteoblast differentiation, and knockin of a mutation in Shn3 that abolishes this interaction resulted in aberrant ERK activation and consequent osteoblast hyperactivity in vivo. Additionally, in vivo genetic interaction studies demonstrated that crossing to Lrp5(-/-) mice partially rescued the osteosclerotic phenotype of Shn3(-/-) mice; mechanistically, this corresponded to the ability of SHN3 to inhibit ERK-mediated suppression of GSK3 beta. Inducible knockdown of Shn3 in adult mice resulted in a high-bone mass phenotype, providing evidence that transient blockade of these pathways in adults holds promise as a therapy for osteoporosis. C1 [Shim, Jae-Hyuck] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Greenblatt, Matthew B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Zou, Weiguo] Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China. [Huang, Zhiwei] Harbin Inst Technol, BIO X Ctr, Harbin 150006, Peoples R China. [Wein, Marc N.; Hu, Dorothy] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Brady, Nicholas] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Brady, Nicholas] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Charron, Jean] Univ Laval, Ctr Rech Cancerol, Quebec City, PQ, Canada. [Brodkin, Heather R.; Petsko, Gregory A.] Brandeis Univ, Dept Biochem, Waltham, MA 02254 USA. [Zaller, Dennis; Jones, Dallas C.] Merck Res Labs, Boston, MA USA. [Zhai, Bo; Gygi, Steven] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. RP Shim, JH (reprint author), Weill Cornell Med Coll, 1300 York Ave E907, New York, NY 10065 USA. EM jas2060@med.cornell.edu; lglimche@med.cornell.edu RI Charron, Jean/A-9792-2013; OI Charron, Jean/0000-0002-5133-0056; Brady, Nicholas/0000-0002-2928-0232 FU NIH [HD055601, K99AR055668]; Arthritis Foundation; NRSA postdoctoral fellowship (DFCI/NCI) [T32 CA070083] FX We thank Henry Kronenberg and Antonios Aliprantis for helpful discussions and Michelle Schweitzer, Pamela Okerholm, Rebecca Drapp, Chantel Lester, Heather De Rivera, Christina Raekyung Lee, Yeon-Suk Yang, Alfred Zullo, and Kirsten Sigrist for technical support. We also thank the many individuals who provided valuable reagents. This work was supported by NIH grants HD055601 (to L.H. Glimcher) and K99AR055668 (to D.C. Jones). J.-H. Shim was supported by a fellowship from the Arthritis Foundation and by an NRSA postdoctoral fellowship (DFCI/NCI T32 CA070083). NR 36 TC 10 Z9 10 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2013 VL 123 IS 9 BP 4010 EP 4022 DI 10.1172/JCI69443 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 220DQ UT WOS:000324562600042 PM 23945236 ER PT J AU Cankovic, M Nikiforova, MN Snuderl, M Adesina, AM Lindeman, N Wen, PY Lee, EQ AF Cankovic, Milena Nikiforova, Marina N. Snuderl, Matija Adesina, Adekunle M. Lindeman, Neal Wen, Patrick Y. Lee, Eudocia Q. TI The Role of MGMT Testing in Clinical Practice A Report of the Association for Molecular Pathology SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID LOW-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA; ISLAND METHYLATOR PHENOTYPE; PHASE-III TRIAL; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE EXPRESSION; CARMUSTINE PLUS O-6-BENZYLGUANINE; PROGRESSIVE MALIGNANT GLIOMA; IN-SITU HYBRIDIZATION; NERVOUS-SYSTEM TUMORS; PROMOTER METHYLATION AB Recent advances in modern molecular technologies allow for the examination and measurement of cancer-related genomic changes. The number of molecular tests for evaluation of diagnostic, prognostic, or predictive markers is expected to increase. In recent years, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been firmly established as a biomarker in patients diagnosed with gliomas, for both clinical trials and routine clinical management. Similarly, molecular markers, such as loss of heterozygosity (LOH) for 1p/19q have already demonstrated clinical utility in treatment of oligodendroglial tumors, and others might soon show clinical utility. Furthermore, nonrandom associations are being discovered among MGMT, 1p/19q LOH, isocitrate dehydrogenase (IDH) mutations, and other tumor-specific modifications that could possibly enhance our ability to predict outcome and response to therapy. While pathologists are facing new and more complicated requests for clinical genomic testing, clinicians are challenged with increasing numbers of molecular data coming from molecular pathology and genomic medicine. Both pathologists and oncologists need to understand the clinical utility of molecular tests and test results, including issues of turnaround time, and their impact on the application of targeted treatment regimens. This review summarizes the existing data that support the rationale for MGMT promoter methylation testing and possibly other molecular testing in clinically defined glioma subtypes. Various molecular testing platforms for evaluation of MGMT methylation status are also discussed. C1 [Cankovic, Milena] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA. [Nikiforova, Marina N.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Snuderl, Matija] NYU, Dept Pathol, Langone Med Ctr, New York, NY USA. [Snuderl, Matija] NYU, Sch Med, New York, NY USA. [Adesina, Adekunle M.] Texas Childrens Hosp, Baylor Coll Med, Neuropathol Program, Houston, TX 77030 USA. [Adesina, Adekunle M.] Texas Childrens Hosp, Baylor Coll Med, Mol Neuropathol Lab, Houston, TX 77030 USA. [Lindeman, Neal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wen, Patrick Y.; Lee, Eudocia Q.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Wen, Patrick Y.; Lee, Eudocia Q.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Cankovic, M (reprint author), Henry Ford Hosp, Dept Pathol & Lab Med, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM mcankov1@hfhs.org RI Waha, Andreas/J-2950-2014; OI Snuderl, Matija/0000-0003-0752-0917 FU Association for Molecular Pathology FX Supported by the Association for Molecular Pathology. NR 112 TC 19 Z9 19 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD SEP PY 2013 VL 15 IS 5 BP 539 EP 555 DI 10.1016/j.jmoldx.2013.05.011 PG 17 WC Pathology SC Pathology GA 210YI UT WOS:000323870900001 PM 23871769 ER PT J AU Rosman, DA Farinhas, JM Ullrich, CG McGinty, G AF Rosman, David A. Farinhas, Joaquim M. Ullrich, Christopher G. McGinty, Geraldine TI Accountable Care Organizations: Is the Radiologist at Risk? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Rosman, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farinhas, Joaquim M.] Montefiore Med Ctr, Dept Radiol, Bronx, NY 10467 USA. [Ullrich, Christopher G.] Charlotte Radiol PA, Charlotte, NC USA. [McGinty, Geraldine] NRAD Med Associates, Dept Radiol, Garden City, NY USA. RP Rosman, DA (reprint author), Massachusetts Gen Hosp, Dept Diagnost Radiol, 55 Fruit St, Boston, MA 02114 USA. EM darosman@gmail.com OI McGinty, Geraldine/0000-0001-6111-2514 NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2013 VL 10 IS 9 BP 645 EP 646 DI 10.1016/j.jacr.2013.01.028 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222IB UT WOS:000324723300004 PM 23664064 ER PT J AU Rosenzweig, KE Chang, JY Chetty, IJ Decker, RH Ginsburg, ME Kestin, LL Kong, FM Lally, BE Langer, CJ Movsas, B Videtic, GMM Willers, H AF Rosenzweig, Kenneth E. Chang, Joe Yujiao Chetty, Indrin J. Decker, Roy H. Ginsburg, Mark E. Kestin, Larry L. Kong, Feng-Ming (Spring) Lally, Brian E. Langer, Corey J. Movsas, Benjamin Videtic, Gregory M. M. Willers, Henning TI ACR Appropriateness Criteria Nonsurgical Treatment for Non-Small-Cell Lung Cancer: Poor Performance Status or Palliative Intent SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; non-small-cell lung cancer; radiation therapy; palliation ID PHASE-III TRIAL; CONFORMAL RADIATION-THERAPY; LIMITED FIELD IRRADIATION; DOSE-VOLUME HISTOGRAM; QUALITY-OF-LIFE; STAGE-I; ONCOLOGY-GROUP; RANDOMIZED-TRIAL; SUPPORTIVE CARE; CONCURRENT CHEMOTHERAPY AB Radiation therapy plays a potential curative role in the treatment of patients with non-small-cell lung cancer with locoregional disease who are not surgical candidates and a palliative role for patients with metastatic disease. Stereotactic body radiation therapy is a relatively new technique in patients with early-stage non-small-cell lung cancer. A trial from RTOG(R) reported >97% local control at 3 years. For patients with locally advanced disease, thoracic radiation to a dose of 60 Gy remains the standard of care. Sequential chemotherapy or radiation alone can be used for patients with poor performance status who cannot tolerate more aggressive approaches. Chemotherapy should be used for patients with metastatic disease. Radiation therapy is useful for palliation of symptomatic tumors, and a dose of approximately 30 Gy is commonly used. Endobronchial brachytherapy is useful for patients with symptomatic endobronchial tumors. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 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 in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Rosenzweig, Kenneth E.] Mt Sinai Sch Med, New York, NY USA. [Chang, Joe Yujiao] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chetty, Indrin J.; Movsas, Benjamin] Henry Ford Hlth Syst, Detroit, MI USA. [Decker, Roy H.] Yale Univ, Sch Med, New Haven, CT USA. [Ginsburg, Mark E.] Columbia Univ, New York, NY USA. [Ginsburg, Mark E.] Soc Thorac Surg, Chicago, IL USA. [Kestin, Larry L.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Kong, Feng-Ming (Spring)] VA Hlth Ctr, Ann Arbor, MI USA. [Kong, Feng-Ming (Spring)] Univ Michigan, Ann Arbor, MI 48109 USA. [Lally, Brian E.] Univ Miami, Miami, FL USA. [Langer, Corey J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Langer, Corey J.] Amer Soc Clin Oncol, Alexandria, VA USA. [Videtic, Gregory M. M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Willers, Henning] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenzweig, KE (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM kenneth.rosenzweig@mountsinai.org FU Varian, Inc (Palo Alto, California); Philips Medical Systems (Andover, Massachusetts); Resonant Medical, Inc (Montreal, Quebec, Canada) FX Dr Movsas has received research support to the Department of Radiation Oncology at Henry Ford Health System from Varian, Inc (Palo Alto, California); Philips Medical Systems (Andover, Massachusetts); and Resonant Medical, Inc (Montreal, Quebec, Canada). NR 79 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2013 VL 10 IS 9 BP 654 EP 664 DI 10.1016/j.jacr.2013.05.031 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222IB UT WOS:000324723300007 PM 23890874 ER PT J AU Patti, JA AF Patti, John A. TI 2013 ACR Presidential Address: A Personal View on the Future of Radiology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Presidential address; future of radiology; change leadership; visions patients AB In this address, John A. Patti, MD, acknowledges the celebration and success that radiologists have experienced throughout their careers but also asks incisive questions about how they will face the future. Answers to those questions require an analysis of the past, an understanding of the present, serious and penetrating introspection, and engagement of a process for moving forward. An understanding of who we are and why we do what we do is essential to facilitate the changes that will be necessary if radiologists are to control the future, rather than having the future control radiologists. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 4 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2013 VL 10 IS 9 BP 665 EP 671 DI 10.1016/j.jacr.2013.06.001 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222IB UT WOS:000324723300008 PM 24007606 ER PT J AU Iyer, RS Bhargava, P Sandstrom, CK Dicks, DL Reddy, GP AF Iyer, Ramesh S. Bhargava, Puneet Sandstrom, Claire K. Dicks, Demetrius L. Reddy, Gautham P. TI Establishing a Fellowship Education Committee SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID DIAGNOSTIC-RADIOLOGY; RESIDENTS; PROGRAMS C1 [Iyer, Ramesh S.] Seattle Childrens Hosp, Dept Radiol, Seattle, WA USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. [Sandstrom, Claire K.; Dicks, Demetrius L.; Reddy, Gautham P.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98105 USA. RP Iyer, RS (reprint author), Univ Washington, Sch Med, Seattle Childrens Hosp, 4800 Sand Point Way NE, Seattle, WA 98105 USA. EM riyer@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 16 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2013 VL 10 IS 9 BP 718 EP 720 DI 10.1016/j.jacr.2012.07.024 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 222IB UT WOS:000324723300018 PM 23332609 ER PT J AU Banks, WA AF Banks, William A. TI Artificial Emotions: Robots Caring for the Elderly SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material ID ANIMAL-ASSISTED THERAPY; LONELINESS; DOGS C1 [Banks, William A.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Banks, WA (reprint author), VA PSH CSI GRECC S-182,Bldg 1,Rm 810A,1600 S Colu, Seattle, WA 98108 USA. EM wabanks1@u.washington.edu NR 8 TC 3 Z9 3 U1 3 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2013 VL 14 IS 9 BP 635 EP 636 DI 10.1016/j.jamda.2013.04.011 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 217AS UT WOS:000324329500003 PM 23764538 ER PT J AU Boockvar, K Signor, D Ramaswamy, R Hung, W AF Boockvar, Kenneth Signor, Daniel Ramaswamy, Ravishankar Hung, William TI Delirium During Acute Illness in Nursing Home Residents SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Nursing homes; delirium; nosocomial infection; activities of daily living ID CONFUSION ASSESSMENT METHOD; ELDERLY MEDICAL PATIENTS; PREDICTIVE MODEL; SYMPTOMS; PREVALENCE; PERSISTENT; MORTALITY; SCALE; RISK; CARE AB Objectives: To ascertain the incidence of delirium during acute illness in nursing home residents, describe the timing of delirium after acute illness onset, describe risk factors for delirium, and explore the relationship between delirium and complications of acute illness. Design: Prospective observational cohort study. Setting: Three nursing homes in metropolitan New York. Participants: Individuals who were expected to remain in the nursing home for at least 2 months, who, as part of a parent study, were receiving opioids, antidepressants, or antipsychotics on a routine basis, and who did not have an acute medical illness at the time of screening. Acute illness surveillance was performed twice weekly through communication with nursing home nursing staff and medical providers using established clinical criteria for incipient cases. Measurements: We followed patients for 14 days after illness onset, and, if applicable, an additional 14 days each after hospital admission and hospital discharge. Delirium was assessed 3 times weekly using the Confusion Assessment Method (CAM). Physical function decline was calculated using change in the Minimum Data Set Activities of Daily Living Scale (MDS-ADL) and cognitive function decline using change in the Minimum Data Set Cognitive performance scale (MDS-CPS). Falls were ascertained by record review. Results: Among 136 nursing home patients followed for a mean of 11.7 months, 78 experienced 232 acute illnesses, of which 162 (71%) were managed in the nursing home. The most common diagnoses were urinary tract infection (20%), cellulitis (15%), and lower respiratory tract infection (9%). Subjects experienced delirium during 41 (17.7%) of 232 acute illnesses. Female sex was associated with a greater risk of delirium (odds ratio 2.59; 95% confidence interval [CI] 1.04-6.43) but there were no other risk factors identified. Delirium was a risk factor for cognitive function decline (odds ratio 4.59; 95% CI 1.99-10.59; P = .0004), but not ADL function decline or falling. Conclusion: Delirium occurred frequently as a complication of acute illness in the nursing home, and was a risk factor for cognitive function decline. This finding supports the rationale to target individuals at the onset of an acute medical problem in the design of interventions to prevent delirium in the nursing home setting. Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc. C1 [Boockvar, Kenneth; Signor, Daniel; Hung, William] James J Peters VA Med Ctr, Bronx, NY USA. [Boockvar, Kenneth] Jewish Home Lifecare, New York, NY 10025 USA. [Boockvar, Kenneth; Ramaswamy, Ravishankar; Hung, William] Mt Sinai, Icahn Sch Med, New York, NY USA. RP Boockvar, K (reprint author), Jewish Home Lifecare, 120 West 106th St, New York, NY 10025 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU VA Health Services Research and Development Grants [ARCD 03-027-1, REA 08-260]; Greenwall Foundation FX This study was funded by VA Health Services Research and Development Grants ARCD 03-027-1 and REA 08-260. Dr. Boockvar was supported by the Greenwall Foundation. NR 34 TC 15 Z9 15 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2013 VL 14 IS 9 BP 656 EP 660 DI 10.1016/j.jamda.2013.06.004 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 217AS UT WOS:000324329500008 PM 23896369 ER PT J AU Yoo, JW Choi, JB Kim, SJ Shin, HP Kim, K Ryu, WS Min, TJ Kim, S Nakagawa, S AF Yoo, Ji Won Choi, Jong Bum Kim, Sun Jung Shin, Hyun P. Kim, Kyudam Ryu, Woo Sang Min, Too Jae Kim, Sulgi Nakagawa, Shunichi TI Factors Associated With Remaining in a Skilled Nursing Facility for Over 90 Days from Admission: Residents' Participation in Therapy and Desire to Return to the Community SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Nursing home; patient participation; skilled nursing facility ID MINIMUM DATA SET; HOME RESIDENTS; DETERMINANTS; TRANSITIONS; POSTACUTE; DELIRIUM AB Background: To identify the factors associated with stay in a skilled nursing facility (SNF) among new enrollees who did not fully participate in therapy sessions. Methods: Data (n = 36,133) were obtained from the Minimum Data Set version 2.0 in the state of Michigan in 2009. Study participants were new SNF enrollees (n = 699) who did not fully participate in therapy sessions despite their desire to return to the community. Multivariate logistic regressions were performed to identify factors contributing to remaining in a nursing home for 91 days or longer. Results: New SNF enrollees were more likely to remain in nursing home when they were depressed (odds ratio [OR] 1.41; 95% confidence interval [CI], 1.09-2.08; P = .01), experiencing delirium (OR = 3.20; 95% CI, 1.48-5.92; P < .001), were not in pain (OR = 0.83; 95% CI, 0.60-0.95; P = .03), or in less complex care (OR = 0.57; 95% CI, 0.44-0.81; P < .01). Conclusions: A higher number of new SNF enrollees than previously reported were likely to stay in nursing homes (28.0%). Depression and delirium were associated with stay in an SNF, while pain and higher complexity of care were associated with returning to the community. Copyright (C) 2013 - American Medical Directors Association, Inc. C1 [Yoo, Ji Won] Aurora Hlth Care, Ctr Senior Hlth & Longev, Milwaukee, WI USA. [Yoo, Ji Won] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Choi, Jong Bum] Yonsei Univ, Coll Med, Dept Pain Med & Anesthesia, Seoul, South Korea. [Kim, Sun Jung] Yonsei Univ, Coll Med, Dept Publ Hlth, Seoul, South Korea. [Kim, Sun Jung] Yonsei Univ, Coll Med, Inst Hlth Serv Res, Seoul, South Korea. [Shin, Hyun P.] Kyung Hee Univ, Coll Med, East West Neo Med Ctr, Dept Internal Med, Seoul, South Korea. [Kim, Kyudam] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. [Ryu, Woo Sang] Korea Univ, Coll Med, Clin Res Ctr, Seoul 136705, South Korea. [Min, Too Jae] Korea Univ, Coll Med, Dept Pain Med & Anesthesia, Seoul 136705, South Korea. [Kim, Sulgi] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Nakagawa, Shunichi] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Nakagawa, Shunichi] James J Peters Vet Affairs Med Ctr, Ctr Clin, Bronx, NY USA. RP Yoo, JW (reprint author), Univ Michigan, Sch Med, Dept Internal Med, 300 North Ingalls Bldg,Room 932, Ann Arbor, MI 48109 USA. EM yoojiw@trinity-health.org NR 20 TC 1 Z9 1 U1 10 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD SEP PY 2013 VL 14 IS 9 AR UNSP 710.e1 DI 10.1016/j.jamda.2013.05.022 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 217AS UT WOS:000324329500020 PM 23860264 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI A parameterization method and application in breast tomosynthesis dosimetry SO MEDICAL PHYSICS LA English DT Article DE mammography; breast tomosynthesis; mean glandular dose; conversion factor; parameterization ID MAMMOGRAPHY; PROTOCOLS; SYSTEM; UK AB Purpose: To present a parameterization method based on singular value decomposition (SVD), and to provide analytical parameterization of the mean glandular dose (MGD) conversion factors from eight references for evaluating breast tomosynthesis dose in the Mammography Quality Standards Act (MQSA) protocol and in the UK, European, and IAEA dosimetry protocols. Methods: MGD conversion factor is usually listed in lookup tables for the factors such as beam quality, breast thickness, breast glandularity, and projection angle. The authors analyzed multiple sets of MGD conversion factors from the Hologic Selenia Dimensions quality control manual and seven previous papers. Each data set was parameterized using a one-to three-dimensional polynomial function of 2-16 terms. Variable substitution was used to improve accuracy. A least-squares fit was conducted using the SVD. Results: The differences between the originally tabulated MGD conversion factors and the results computed using the parameterization algorithms were (a) 0.08%-0.18% on average and 1.31% maximum for the Selenia Dimensions quality control manual, (b) 0.09%-0.66% on average and 2.97% maximum for the published data by Dance et al. [Phys. Med. Biol. 35, 1211-1219 (1990); 45, 3225-3240 (2000); 54, 4361-4372 (2009); 56, 453-471 (2011)], (c) 0.74%-0.99% on average and 3.94% maximum for the published data by Sechopoulos et al. [Med. Phys. 34, 221-232 (2007); J. Appl. Clin. Med. Phys. 9, 161-171 (2008)], and (d) 0.66%-1.33% on average and 2.72% maximum for the published data by Feng and Sechopoulos [Radiology 263, 35-42 (2012)], excluding one sample in (d) that does not follow the trends in the published data table. Conclusions: A flexible parameterization method is presented in this paper, and was applied to breast tomosynthesis dosimetry. The resultant data offer easy and accurate computations of MGD conversion factors for evaluating mean glandular breast dose in the MQSA protocol and in the UK, European, and IAEA dosimetry protocols. Microsoft Excel (TM) spreadsheets are provided for the convenience of readers. (C) 2013 American Association of Physicists in Medicine. C1 [Liu, Bob] Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Webster Ctr Adv Res & Educ Radiat, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 19 TC 2 Z9 3 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2013 VL 40 IS 9 AR 092105 DI 10.1118/1.4818059 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CV UT WOS:000324259800043 PM 24007174 ER PT J AU Rottmann, J Keall, P Berbeco, R AF Rottmann, Joerg Keall, Paul Berbeco, Ross TI Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery SO MEDICAL PHYSICS LA English DT Article DE lung cancer; EPID; motion; real-time; tracking ID RESPIRATORY MOTION; TRACKING; MANAGEMENT; SURROGATE; PHANTOM; SYSTEM AB Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient. Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 x 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps. Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (approximate to 20 mm tumor motion range) is 1.0 mm. Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time. (C) 2013 American Association of Physicists in Medicine. C1 [Rottmann, Joerg; Berbeco, Ross] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rottmann, Joerg; Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Keall, Paul] Univ Sydney, Sydney Med Sch, Radiat Phys Lab, Sydney, NSW 2006, Australia. RP Rottmann, J (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM jrottmann@lroc.harvard.edu FU National Cancer Institute [R21CA156068] FX The project described was supported, in part, by Award Number R21CA156068 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 20 TC 12 Z9 12 U1 0 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2013 VL 40 IS 9 AR 091713 DI 10.1118/1.4818655 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CV UT WOS:000324259800015 PM 24007146 ER PT J AU Seco, J Oumano, M Depauw, N Dias, MF Teixeira, RP Spadea, MF AF Seco, Joao Oumano, Michael Depauw, Nicolas Dias, Marta F. Teixeira, Rui P. Spadea, Maria F. TI Characterizing the modulation transfer function (MTF) of proton/carbon radiography using Monte Carlo simulations SO MEDICAL PHYSICS LA English DT Article DE proton radiography; carbon ion beam radiography; proton imaging; carbon ion beam imaging ID PROTON COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; TOOLKIT; DENSITY; DESIGN; SYSTEM AB Purpose: To characterize the modulation transfer function (MTF) of proton/carbon radiography using Monte Carlo simulations. To assess the spatial resolution of proton/carbon radiographic imaging. Methods: A phantom was specifically modeled with inserts composed of two materials with three different densities of bone and lung. The basic geometry of the phantom consists of cube-shaped inserts placed in water. The thickness of the water, the thickness of the cubes, the depth of the cubes in the water, and the particle beam energy have all been varied and studied. There were two phantom thicknesses considered 20 and 28 cm. This represents an average patient thickness and a thicker sized patient. Radiographs were produced for proton beams at 230 and 330 MeV and for a carbon ion beam at 400 MeV per nucleon. The contrast-to-noise ratio (CNR) was evaluated at the interface of two materials on the radiographs, i.e., lung-water and bone-water. The variation in CNR at interface between lung-water and bone-water were study, where a sigmoidal fit was performed between the lower and the higher CNR values. The full width half-maximum (FWHM) value was then obtained from the sigmoidal fit. Ultimately, spatial resolution was defined by the 10% point of the modulation-transfer-function (MTF10%), in units of line-pairs per mm (lp/mm). Results: For the 20 cm thick phantom, the FWHM values varied between 0.5 and 0.7 mm at the lung-water and bone-water interfaces, for the proton beam energies of 230 and 330 MeV and the 400 MeV/n carbon beam. For the 28 cm thick phantom, the FWHM values varied between 0.5 and 1.2 mm at the lung-water and bone-water interface for the same inserts and beam energies. For the 20 cm phantom the MTF10% for lung-water interface is 2.3, 2.4, and 2.8 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. For the same 20 cm thick phantom but for the bone-water interface the MTF10% yielded 1.9, 2.3, and 2.7 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. In the case of the thicker 28 cm phantom, the authors observed that at the lung-water interface the MTF10% is 1.6, 1.9, and 2.6 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. While for the bonewater interface the MTF10% was 1.4, 1.9, and 2.9 lp/mm, respectively, for 230, 330, and 400 MeV/n beams. Conclusions: Carbon radiography (400 MeV/n) yielded best spatial resolution, with MTF10% = 2.7 and 2.8 lp/mm, respectively, at the lung-water and bone-water interfaces. The spatial resolution of the 330 MeV proton beam was better than the 230 MeV proton, because higher incident proton energy suffer smaller deflections within the patient and thus yields better proton radiographic images. The authors also observed that submillimeter resolution can be obtained with both proton and carbon beams. (C) 2013 American Association of Physicists in Medicine. C1 [Seco, Joao; Depauw, Nicolas] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Oumano, Michael] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. [Depauw, Nicolas] Univ Wollongong, CMRP, Wollongong, NSW 2522, Australia. [Dias, Marta F.; Teixeira, Rui P.] Univ Lisbon, Dept Biomed Engn & Biophys, P-1649004 Lisbon, Portugal. [Spadea, Maria F.] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. RP Seco, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. EM JSECO@PARTNERS.ORG NR 18 TC 7 Z9 7 U1 0 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2013 VL 40 IS 9 AR 091717 DI 10.1118/1.4819816 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CV UT WOS:000324259800019 PM 24007150 ER PT J AU St James, S Seco, J Mishra, P Lewis, JH AF St James, Sara Seco, Joao Mishra, Pankaj Lewis, John H. TI Simulations using patient data to evaluate systematic errors that may occur in 4D treatment planning: A proof of concept study SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo treatment planning; 4D treatment planning ID MONTE-CARLO SIMULATIONS; REAL-TIME TUMOR; RESPIRATORY MOTION; RADIATION-THERAPY; BODY RADIOTHERAPY; LUNG-TUMORS; TRACKING; PHANTOM; INTRAFRACTION; MANAGEMENT AB Purpose: The purpose of this work is to present a framework to evaluate the accuracy of four-dimensional treatment planning in external beam radiation therapy using measured patient data and digital phantoms. Methods: To accomplish this, 4D digital phantoms of two model patients were created using measured patient lung tumor positions. These phantoms were used to simulate a four-dimensional computed tomography image set, which in turn was used to create a 4D Monte Carlo (4DMC) treatment plan. The 4DMC plan was evaluated by simulating the delivery of the treatment plan over approximately 5 min of tumor motion measured from the same patient on a different day. Unique phantoms accounting for the patient position (tumor position and thorax position) at 2 s intervals were used to represent the model patients on the day of treatment delivery and the delivered dose to the tumor was determined using Monte Carlo simulations. Results: For Patient 1, the tumor was adequately covered with 95.2% of the tumor receiving the prescribed dose. For Patient 2, the tumor was not adequately covered and only 74.3% of the tumor received the prescribed dose. Conclusions: This study presents a framework to evaluate 4D treatment planning methods and demonstrates a potential limitation of 4D treatment planning methods. When systematic errors are present, including when the imaging study used for treatment planning does not represent all potential tumor locations during therapy, the treatment planning methods may not adequately predict the dose to the tumor. This is the first example of a simulation study based on patient tumor trajectories where systematic errors that occur due to an inaccurate estimate of tumor motion are evaluated. (C) 2013 American Association of Physicists in Medicine. C1 [St James, Sara; Mishra, Pankaj; Lewis, John H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Seco, Joao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP St James, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. EM sara.stjames@gmail.com NR 24 TC 3 Z9 3 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2013 VL 40 IS 9 AR 091706 DI 10.1118/1.4817244 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CV UT WOS:000324259800008 PM 24007139 ER PT J AU Unkelbach, J Zeng, C Engelsman, M AF Unkelbach, Jan Zeng, Chuan Engelsman, Martijn TI Simultaneous optimization of dose distributions and fractionation schemes in particle radiotherapy SO MEDICAL PHYSICS LA English DT Article DE proton therapy optimization; non-uniform fractionation; biologically equivalent dose AB Purpose: The paper considers the fractionation problem in intensity modulated proton therapy (IMPT). Conventionally, IMPT fields are optimized independently of the fractionation scheme. In this work, we discuss the simultaneous optimization of fractionation scheme and pencil beam intensities. Methods: This is performed by allowing for distinct pencil beam intensities in each fraction, which are optimized using objective and constraint functions based on biologically equivalent dose (BED). The paper presents a model that mimics an IMPT treatment with a single incident beam direction for which the optimal fractionation scheme can be determined despite the nonconvexity of the BED-based treatment planning problem. Results: For this model, it is shown that a small alpha/beta ratio in the tumor gives rise to a hypofractionated treatment, whereas a large alpha/beta ratio gives rise to hyperfractionation. It is further demonstrated that, for intermediate alpha/beta ratios in the tumor, a nonuniform fractionation scheme emerges, in which it is optimal to deliver different dose distributions in subsequent fractions. The intuitive explanation for this phenomenon is as follows: By varying the dose distribution in the tumor between fractions, the same total BED can be achieved with a lower physical dose. If it is possible to achieve this dose variation in the tumor without varying the dose in the normal tissue (which would have an adverse effect), the reduction in physical dose may lead to a net reduction of the normal tissue BED. For proton therapy, this is indeed possible to some degree because the entrance dose is mostly independent of the range of the proton pencil beam. Conclusions: The paper provides conceptual insight into the interdependence of optimal fractionation schemes and the spatial optimization of dose distributions. It demonstrates the emergence of nonuniform fractionation schemes that arise from the standard BED model when IMPT fields and fractionation scheme are optimized simultaneously. Although the projected benefits are likely to be small, the approach may give rise to an improved therapeutic ratio for tumors treated with stereotactic techniques to high doses per fraction. (C) 2013 American Association of Physicists in Medicine. C1 [Unkelbach, Jan; Zeng, Chuan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan; Zeng, Chuan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Engelsman, Martijn] Delft Univ Technol, HollandPTC, Fac Appl Phys, NL-2628 CJ Delft, Netherlands. RP Unkelbach, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM junkelbach@partners.org FU Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 10 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 2013 VL 40 IS 9 AR 091702 DI 10.1118/1.4816658 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CV UT WOS:000324259800004 PM 24007135 ER PT J AU Du, Z Li, H Wei, Q Zhao, X Wang, CC Zhu, QL Yi, X Xu, WY Liu, XS Jin, WW Su, Z AF Du, Zhou Li, Hui Wei, Qiang Zhao, Xin Wang, Chunchao Zhu, Qilin Yi, Xin Xu, Wenying Liu, X. Shirley Jin, Weiwei Su, Zhen TI Genome-Wide Analysis of Histone Modifications: H3K4me2, H3K4me3, H3K9ac, and H3K27ac in Oryza sativa L. Japonica SO MOLECULAR PLANT LA English DT Article DE bioinformatics; chromatin structure and remodeling; epigenetics; gene regulation; genomics; rice ID H3 LYSINE 4; ARABIDOPSIS-THALIANA; DNA-BINDING; TRANSCRIPTIONAL REGULATION; CHROMATIN MODIFICATIONS; REGULATORY ELEMENT; PATTERNS; CHIP; METHYLATIONS; EXPRESSION AB H3K4me2/3, H3K9ac, and H3K27ac investigated by ChIP-Seq showed enrichment in generic regions and transcription start sites, and associated with active transcription in rice. They were used to discover unannotated genes and to predict transcription factor binding sites together with DNase-Seq data.While previous studies have shown that histone modifications could influence plant growth and development by regulating gene transcription, knowledge about the relationships between these modifications and gene expression is still limited. This study used chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq), to investigate the genome-wide distribution of four histone modifications: di and trimethylation of H3K4 (H3K4me2 and H3K4me3) and acylation of H3K9 and H3K27 (H3K9ac and H3K27ac) in Oryza sativa L. japonica. By analyzing published DNase-Seq data, this study explored DNase-Hypersensitive (DH) sites along the rice genome. The histone marks appeared mainly in generic regions and were enriched around the transcription start sites (TSSs) of genes. This analysis demonstrated that the four histone modifications and the DH sites were all associated with active transcription. Furthermore, the four histone modifications were highly concurrent with transcript regionsua promising feature that was used to predict missing genes in the rice gene annotation. The predictions were further validated by experimentally confirming the transcription of two predicted missing genes. Moreover, a sequence motif analysis was constructed in order to identify the DH sites and many putative transcription factor binding sites. C1 [Du, Zhou; Wei, Qiang; Wang, Chunchao; Yi, Xin; Xu, Wenying; Su, Zhen] China Agr Univ, Coll Biol Sci, State Key Lab Plant Physiol & Biochem, Beijing 100193, Peoples R China. [Li, Hui; Zhao, Xin; Zhu, Qilin; Jin, Weiwei] China Agr Univ, Minist Agr, Key Lab Biol & Genet Improvement Maize, Natl Maize Improvement Ctr China, Beijing 100193, Peoples R China. [Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Su, Z (reprint author), China Agr Univ, Coll Biol Sci, State Key Lab Plant Physiol & Biochem, Beijing 100193, Peoples R China. EM xsliu@jimmy.harvard.edu; weiweijin@cau.edu.cn; zhensu@cau.edu.cn FU Natural Science Foundation of China [31071125, 31025018, 31028011]; Ministry of Education of China [NCET-09-0735]; National Institutes of Health of US [GM99409] FX This work was supported by grants from the Natural Science Foundation of China (31071125, 31025018, and 31028011) and the Ministry of Education of China (NCET-09-0735), as well as the National Institutes of Health of US (grant no. GM99409). NR 39 TC 21 Z9 23 U1 4 U2 31 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1674-2052 J9 MOL PLANT JI Mol. Plant. PD SEP PY 2013 VL 6 IS 5 BP 1463 EP 1472 DI 10.1093/mp/sst018 PG 10 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 223SK UT WOS:000324829400008 PM 23355544 ER PT J AU Spaeter, D Abramczuk, MK Buac, K Zangi, L Stachel, MW Clarke, J Sahara, M Ludwig, A Chien, KR AF Spaeter, Daniela Abramczuk, Monika K. Buac, Kristina Zangi, Lior Stachel, Maxine W. Clarke, Jonathan Sahara, Makoto Ludwig, Andreas Chien, Kenneth R. TI A HCN4+cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells SO NATURE CELL BIOLOGY LA English DT Article ID CARDIAC CONDUCTION SYSTEM; MOUSE HEART; CARDIOVASCULAR PROGENITORS; CHANNEL HCN4; EXPRESSION; LINEAGES; ISL1; DIFFERENTIATION; VENTRICLE; SEPARATE AB Most of the mammalian heart is formed from mesodermal progenitors in the first and second heart fields (FHF and SHF), whereby the FHF gives rise to the left ventricle and parts of the atria and the SHF to the right ventricle, outflow tract and parts of the atria(1-3). Whereas SHF progenitors have been characterized in detail, using specific molecular markers(4-8), comprehensive studies on the FHF have been hampered by the lack of exclusive markers. Here, we present Hcn4 (hyperpolarization-activated cyclic nucleotide-gated channel 4) as an FHF marker. Lineage-traced Hcn4+/FHF cells delineate FHF-derived structures in the heart and primarily contribute to cardiomyogenic cell lineages, thereby identifying an early cardiomyogenic progenitor pool. As a surface marker, HCN4 also allowed the isolation of cardiomyogenic Hcn4+/FHF progenitors from human embryonic stem cells. We conclude that a primary purpose of the FHF is to generate cardiac muscle and support the contractile activity of the primitive heart tube, whereas SHF-derived progenitors contribute to heart cell lineage diversification. C1 [Spaeter, Daniela; Abramczuk, Monika K.; Buac, Kristina; Zangi, Lior; Stachel, Maxine W.; Clarke, Jonathan; Sahara, Makoto; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Spaeter, Daniela; Abramczuk, Monika K.; Buac, Kristina; Zangi, Lior; Stachel, Maxine W.; Sahara, Makoto; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Spaeter, Daniela; Abramczuk, Monika K.; Buac, Kristina; Zangi, Lior; Stachel, Maxine W.; Sahara, Makoto; Chien, Kenneth R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ludwig, Andreas] Univ Erlangen Nurnberg, Inst Expt & Klin Pharmakol & Toxikol, D-91054 Erlangen, Germany. [Chien, Kenneth R.] Karolinska Inst, Dept Cell & Mol Biol & Med, Stockholm, Sweden. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM kenneth.chien@ki.se FU D.F.G. (German Research Foundation); NHLBI [T32HL007208]; NIH [U01 HL098 166, U01H100408] FX We would like to thank C. Cowan for his support, L. Prickett-Rice, K. Folz-Donahue and M. Weglarz of the Harvard Stem Cell Institute Flow Cytometry Core Facility for assistance with FACS analysis, C. Du of the Tufts Electrophysiology Core for assistance with electrophysiology recordings, L. Bu for technical advice, K. Buac, E. Hansson, C. Riedel and L. Bu for critical reading of the manuscript and discussions, and C. Hartmann for advice on double-fluorescence in situ hybridizations. D.S. has received a D.F.G. (German Research Foundation) postdoctoral fellowship. K.B. was supported by a NHLBI T32HL007208 grant. This work is financially supported by the NIH U01 HL098 166 and NIH U01H100408 research grants. NR 41 TC 11 Z9 11 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2013 VL 15 IS 9 BP 1098 EP + DI 10.1038/ncb2824 PG 18 WC Cell Biology SC Cell Biology GA 213IP UT WOS:000324050000010 ER PT J AU Rafeq, Z Roh, JD Guarino, P Kaufman, J Joseph, J AF Rafeq, Z. Roh, J. D. Guarino, P. Kaufman, J. Joseph, J. TI Adverse myocardial effects of B-vitamin therapy in subjects with chronic kidney disease and hyperhomocysteinaemia SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Article DE Homocysteine; Heart failure; Diastolic dysfunction; Chronic kidney disease ID CONGESTIVE-HEART-FAILURE; STAGE RENAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; LEFT ATRIAL VOLUME; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; FOLIC-ACID; HYPERTENSIVE-RATS; RISK; INFARCTION AB Background & aims: Hyperhomocysteinaemia (HHCY), a common finding in patients with chronic kidney disease (CKD), has been shown to contribute to adverse cardiac remodelling and failure. We hypothesised that in human subjects with CKD, HHCY would be associated with myocardial dysfunction, and that homocysteine (HCY)-lowering therapy would improve myocardial remodelling and heart-failure (HF) outcomes. Methods and results: Post hoc analysis of the Homocysteinemia in Kidney and End Stage Renal Disease (HOST) trial (n=2056) was performed to determine if HCY-lowering therapy with high dose B vitamins affects HF outcomes in patients with CKD. In addition, effects on myocardial remodelling were assessed in a subgroup of 220 trial subjects who had transthoracic echocardiograms done before study randomisation and during the course of the study as part of their routine clinical care. HF outcomes were not significantly affected by treatment compared to the placebo. HCY levels were inversely correlated with diastolic function (R= - 0.21; p = 0.038). Vitamin therapy resulted in a significant increase in left atrial size (+0.15 +/- 0.8 cm vs. - 0.13 +/- 0.07 cm; p=0.0095). No other echocardiographic parameters were significantly associated with baseline HCY levels or changes with vitamin therapy. Conclusion: HHCY is associated with diastolic dysfunction in patients with CKD. However, B-vitamin therapy did not improve HF outcomes despite lowering of plasma HCY levels, and was associated with an increase in left atrial size, which is a surrogate for worsening left ventricular diastolic dysfunction. These findings suggest that high-dose B vitamin therapy may be harmful in patients with CKD. Published by Elsevier B.V. C1 [Rafeq, Z.; Kaufman, J.; Joseph, J.] Veteran Affairs Boston Healthcare Syst, Dept Med, Boston, MA USA. [Joseph, J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Roh, J. D.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Roh, J. D.; Joseph, J.] Harvard Univ, Sch Med, Boston, MA USA. [Kaufman, J.; Joseph, J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Guarino, P.] VA Med Ctr, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Cardiol Sect 111, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM jjoseph16@partners.org FU Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development; PamLab; Abbott Laboratories FX The HOST study was supported by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development; PamLab; and Abbott Laboratories. NR 30 TC 5 Z9 7 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD SEP PY 2013 VL 23 IS 9 BP 836 EP 842 DI 10.1016/j.numecd.2012.07.002 PG 7 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA 219VE UT WOS:000324538200006 PM 22902185 ER PT J AU Wo, JY Faris, JE AF Wo, Jennifer Y. Faris, Jason E. TI The Controversial Role of Chemoradiation for Patients With Locally Advanced Pancreatic Cancer SO ONCOLOGIST LA English DT Editorial Material ID COOPERATIVE-ONCOLOGY-GROUP; RADIATION-THERAPY; PHASE-III; GEMCITABINE; ADENOCARCINOMA; 5-FLUOROURACIL; TRIAL; CHEMOTHERAPY; RADIOTHERAPY; FOLFIRINOX C1 [Wo, Jennifer Y.; Faris, Jason E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Cambridge, MA 02138 USA. RP Faris, JE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7E,55 Fruit St, Boston, MA 02114 USA. EM jwo@partners.org; jfaris@partners.org NR 21 TC 1 Z9 1 U1 1 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD SEP PY 2013 VL 18 IS 9 BP 981 EP 985 DI 10.1634/theoncologist.2013-0270 PG 5 WC Oncology SC Oncology GA 223HY UT WOS:000324796500002 ER PT J AU Mullen, JT DeLaney, TF Rosenberg, AE Le, L Iafrate, AJ Kobayashi, W Szymonifka, J Yeap, BY Chen, YL Harmon, DC Choy, E Yoon, SS Raskin, KA Hornicek, FJ Nielsen, GP AF Mullen, John T. DeLaney, Thomas F. Rosenberg, Andrew E. Le, Long Iafrate, A. John Kobayashi, Wendy Szymonifka, Jackie Yeap, Beow Y. Chen, Yen-Lin Harmon, David C. Choy, Edwin Yoon, Sam S. Raskin, Kevin A. Hornicek, Francis J. Nielsen, Gunnlauger P. TI beta-Catenin Mutation Status and Outcomes in Sporadic Desmoid Tumors SO ONCOLOGIST LA English DT Article DE Desmoid tumor; Beta-catenin; Mutation status; CTNNB1; Fibromatosis ID ADENOMATOUS POLYPOSIS; SUPPRESSOR PROTEIN; FIBROMATOSIS; GENE AB Background. Mutations in the gene-encoding beta-catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoid tumors and to determine whether CTNNB1 mutation status correlates with disease outcome. Methods. Single-base extension genotyping of the CTNNB1 gene was performed on 145 sporadic, paraffin-embedded desmoid tumor specimens. Correlation of mutation status with outcome was performed on a subset of 115 patients who underwent macroscopically complete surgical resection. Results. CTNNB1mutationsweredetected in 106 of 145(73%) tumor specimens and in 86 of 115 (75%) specimens from patients who underwent curative-intent surgical resection, including discrete mutations in the following codons of CTNNB1 exon 3: T41A (46%), S45F (25%), S45P (1.7%), and S45C (0.9%). Desmoid tumors of the superficial trunk were significantly less likely to harbor CTNNB1 mutations than tumors located elsewhere, but none of the other examined clinicopathologic factors were found to be associated with CTNNB1 mutation status. At a median follow-up of 31 months, 5-year recurrence-free survival was slightly, although not statistically significantly, worse for patients with beta-catenin-mutated tumors than for those with wild-type tumors (58% vs. 74%, respectively). The specific CTNNB1 codon mutation did not correlate with the risk for recurrence. Conclusion. CTNNB1 mutations are indeed common in sporadic desmoid tumors. However, our study did not detect a statistically significant difference in recurrence risk according to either the CTNNB1 mutation status or the specific CTNNB1 mutation. C1 [Mullen, John T.; Yoon, Sam S.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [DeLaney, Thomas F.; Kobayashi, Wendy; Chen, Yen-Lin] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Rosenberg, Andrew E.; Le, Long; Iafrate, A. John; Nielsen, Gunnlauger P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Szymonifka, Jackie; Yeap, Beow Y.; Harmon, David C.; Choy, Edwin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Raskin, Kevin A.; Hornicek, Francis J.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org FU Federal Share of program income earned by Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research and Treatment Center FX This work was funded in part by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 18 TC 22 Z9 22 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD SEP PY 2013 VL 18 IS 9 BP 1043 EP 1049 DI 10.1634/theoncologist.2012-0449 PG 7 WC Oncology SC Oncology GA 223HY UT WOS:000324796500009 PM 23960186 ER PT J AU Suri, P Hunter, DJ Rainville, J Guermazi, A Katz, JN AF Suri, P. Hunter, D. J. Rainville, J. Guermazi, A. Katz, J. N. TI Presence and extent of severe facet joint osteoarthritis are associated with back pain in older adults SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Zygapophyseal; Lumbar; Arthritis; Intervertebral disc; Spondylosis ID LUMBAR DISC DEGENERATION; ABDOMINAL AORTIC CALCIFICATION; RESONANCE-IMAGING CHANGES; MALE MONOZYGOTIC TWINS; 5-YEAR FOLLOW-UP; RADIOGRAPHIC FEATURES; KNEE OSTEOARTHRITIS; RISK-FACTORS; COMPUTED-TOMOGRAPHY; CORONARY-ARTERY AB Objective: To determine whether the presence and extent of severe lumbar facet joint osteoarthritis (OA) are associated with back pain in older adults, accounting for disc height narrowing and other covariates. Design: Two hundred and fifty-two older adults from the Framingham Offspring Cohort (mean age 67 years) were studied. Participants received standardized computed tomography (CT) assessments of lumbar facet joint OA and disc height narrowing at the L2-S1 interspaces using four-grade semi-quantitative scales. Severe facet joint OA was defined according to the presence and/or degree of joint space narrowing, osteophytosis, articular process hypertrophy, articular erosions, subchondral cysts, and intraarticular vacuum phenomenon. Severe disc height narrowing was defined as marked narrowing with endplates almost in contact. Back pain was defined as participant report of pain on most days or all days in the past 12 months. We used multivariable logistic regression to examine associations between severe facet joint OA and back pain, adjusting for key covariates including disc height narrowing, sociodemographics, anthropometrics, and health factors. Results: Severe facet joint OA was more common in participants with back pain than those without (63.2% vs 46.7%; P = 0.03). In multivariable analyses, presence of any severe facet joint OA remained significantly associated with back pain (odds ratio (OR) 2.15 [95% confidence interval (CI) 1.13-4.08]). Each additional joint with severe OA conferred greater odds of back pain [OR per joint 1.20 (95% CI 1.02-1.41)]. Conclusions: The presence and extent of severe facet joint OA on CT imaging are associated with back pain in community-based older adults, independent of sociodemographics, health factors, and disc height narrowing. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. C1 [Suri, P.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Suri, P.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Suri, P.; Rainville, J.] New England Baptist Hosp, Boston, MA USA. [Hunter, D. J.] Univ Sydney, Kolling Inst, Sydney, NSW 2006, Australia. [Hunter, D. J.] Royal N Shore Hosp, Dept Rheumatol, Sydney, NSW, Australia. [Guermazi, A.] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02118 USA. [Katz, J. N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Katz, J. N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Suri, P.] Spaulding Rehabil Hosp, Boston, MA USA. [Suri, P.] VA Boston Healthcare Syst, Boston, MA USA. RP Suri, P (reprint author), VA Puget Sound Healthcare Syst, Rehabil Care Serv, 1660 S Columbian Way,RCS 117, Seattle, WA 98108 USA. EM pradeep.suri@va.gov; david.hunter@sydney.edu.au; jrainvil@nebh.org; Ali.Guermazi@bmc.org; jnkatz@partners.org FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Rehabilitation Medicine Scientist Training Program (RMSTP); National Institutes of Health [K12 HD 01097]; New England Baptist Hospital Research Funding Award; Elizabeth Stent Fund; NIH/NIAMS [K24 AR 02123, P60 AR 47782]; Australian Research Council Future Fellowship FX From the Framingham Heart Study of the National Heart, Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The National Heart, Lung and Blood Institute's Framingham Heart Study contract (No. N01-HC-25195) supported the recruitment, enrollment, and examination of the Offspring and Third Generation Cohorts and the CT scans. Dr. Suri and this research were funded by the Rehabilitation Medicine Scientist Training Program (RMSTP) and the National Institutes of Health (K12 HD 01097), with supplemental funding from the New England Baptist Hospital Research Funding Award and the Elizabeth Stent Fund. Dr. Katz was funded in part by NIH/NIAMS K24 AR 02123 and NIH/NIAMS P60 AR 47782. Dr. Hunter is funded by an Australian Research Council Future Fellowship. NR 51 TC 14 Z9 14 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2013 VL 21 IS 9 SI SI BP 1199 EP 1206 DI 10.1016/j.joca.2013.05.013 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 225KQ UT WOS:000324962200009 PM 23973131 ER PT J AU Cotofana, S Wyman, BT Benichou, O Dreher, D Nevitt, M Gardiner, J Wirth, W Hitzl, W Kwoh, CK Eckstein, F Frobell, RB AF Cotofana, S. Wyman, B. T. Benichou, O. Dreher, D. Nevitt, M. Gardiner, J. Wirth, W. Hitzl, W. Kwoh, C. K. Eckstein, F. Frobell, R. B. CA OAI Investigators Grp TI Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Pain; Cartilage; MRI; Denuded area of subchondral bone ID INITIATIVE PROGRESSION SUBCOHORT; ARTICULAR-CARTILAGE; IMAGING FINDINGS; OSTEOCHONDRAL JUNCTION; RADIOGRAPHIC FEATURES; SENSORY INNERVATION; REGIONAL-ANALYSIS; OSTEOARTHRITIS; ASSOCIATION; JOINT AB Objective: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. Methods: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 +/- 9.6 yrs, BMI 29.4 +/- 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. Results: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% Cl 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 135-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. Conclusion: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Cotofana, S.; Wirth, W.; Hitzl, W.; Eckstein, F.; Frobell, R. B.] Paracelsus Med Univ, Salzburg, Austria. [Cotofana, S.; Wirth, W.; Eckstein, F.] Chondrometr GmbH, Ainring, Germany. [Wyman, B. T.; Gardiner, J.] Pfizer Inc, Groton, CT 06340 USA. [Benichou, O.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Dreher, D.] Merck Serono, Geneva, Switzerland. [Nevitt, M.] UCSF, San Francisco, CA USA. [Kwoh, C. K.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Kwoh, C. K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Frobell, R. B.] Lund Univ, Dept Orthoped, Clin Sci Lund, Lund, Sweden. RP Cotofana, S (reprint author), PMU, Inst Anat & Musculoskeletal Res, Strubergasse 21, A-5020 Salzburg, Austria. EM sebastian.cotofana@pmu.ac.at RI Wirth, Wolfgang/C-8724-2011 OI Wirth, Wolfgang/0000-0002-2297-8283 FU Pfizer Inc.; Eli Lilly Co; Merck Serono SA - Geneva, Switzerland; GlaxoSmithKline; Centocor Inc.; National Institutes of Health, a branch of the Department of Health and Human Services [N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, N01-AR-2-2262]; Novartis Pharmaceuticals Corporation; Merck Research Laboratories FX The image analysis of this study was funded by an industry consortium consisting of Pfizer Inc., Eli Lilly & Co, Merck Serono SA - Geneva, Switzerland, GlaxoSmithKline, and Centocor Inc.; The OAI is a public-private partnership comprised five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators. Private funding partners include Pfizer Inc.; Novartis Pharmaceuticals Corporation; Merck Research Laboratories; and GlaxoSmithKline. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This manuscript has received the approval of the OAI Publications Committee based on a review of its scientific content and data interpretation. NR 48 TC 11 Z9 11 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2013 VL 21 IS 9 SI SI BP 1214 EP 1222 DI 10.1016/j.joca.2013.04.001 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 225KQ UT WOS:000324962200011 PM 23973133 ER PT J AU Haberer, JE Baeten, JM Campbell, J Wangisi, J Katabira, E Ronald, A Tumwesigye, E Psaros, C Safren, SA Ware, NC Thomas, KK Donnell, D Krows, M Kidoguchi, L Celum, C Bangsberg, DR AF Haberer, Jessica E. Baeten, Jared M. Campbell, James Wangisi, Jonathan Katabira, Elly Ronald, Allan Tumwesigye, Elioda Psaros, Christina Safren, Steven A. Ware, Norma C. Thomas, Katherine K. Donnell, Deborah Krows, Meighan Kidoguchi, Lara Celum, Connie Bangsberg, David R. TI Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa SO PLOS MEDICINE LA English DT Article ID PREEXPOSURE PROPHYLAXIS; PROTEASE INHIBITORS; THERAPY; TRANSMISSION; POPULATION; WOMEN; INDIA AB Background: Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Methods and Findings: Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants-all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p< 0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. Conclusions: The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. C1 [Haberer, Jessica E.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baeten, Jared M.; Thomas, Katherine K.; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Celum, Connie] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Baeten, Jared M.; Celum, Connie] Univ Washington, Dept Med, Seattle, WA USA. [Baeten, Jared M.; Celum, Connie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Campbell, James; Wangisi, Jonathan] US Ctr Dis Control & Prevent, Entebbe, Uganda. [Katabira, Elly] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Ronald, Allan] Univ Manitoba, Dept Infect Dis, Winnipeg, MB, Canada. [Tumwesigye, Elioda] Kabwohe Clin Res Ctr, Kabwohe, Uganda. [Psaros, Christina; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat & Behav Med, Boston, MA 02114 USA. [Psaros, Christina; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ware, Norma C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda. RP Haberer, JE (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM jhaberer@partners.org OI Ronald, Allan/0000-0002-5746-3490; Donnell, Deborah/0000-0002-0587-7480 FU Bill & Melinda Gates Foundation [47674, OOP52516] FX This study and the Partners PrEP Study were supported by the Bill & Melinda Gates Foundation (http://www.gatesfoundation.org; grants 47674 and OOP52516). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 69 Z9 69 U1 1 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD SEP PY 2013 VL 10 IS 9 AR e1001511 DI 10.1371/journal.pmed.1001511 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 224EA UT WOS:000324863700006 PM 24058300 ER PT J AU Klest, B Freyd, JJ Foynes, MM AF Klest, Bridget Freyd, Jennifer J. Foynes, Melissa Ming TI Trauma Exposure and Posttraumatic Symptoms in Hawaii: Gender, Ethnicity, and Social Context SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE betrayal trauma; ethnicity; gender; socioeconomic status; Hawaii ID ADVERSE CHILDHOOD EXPERIENCES; STRESS-DISORDER; QUESTIONNAIRE DATA; VIETNAM VETERANS; MENTAL-HEALTH; ABUSE; COMMUNITY; ADOLESCENTS; DISASTER; EVENTS AB Eight-hundred and 33 members of an ethnically diverse longitudinal cohort study in Hawaii were surveyed about their personal exposure to several types of traumatic events, socioeconomic resources, and mental health symptoms. Results replicated findings from prior research that while men and women are exposed to similar rates of trauma overall, women report more exposure to traumas high in betrayal (HB), while men report exposure to more traumas lower in betrayal (LB). Trauma exposure was predictive of mental health symptoms, with neglect, household dysfunction, and HB traumas predicting symptoms of depression, anxiety, PTSD, dissociation, and sleep disturbance, and LB traumas predicting PTSD and dissociation symptoms. Native Hawaiian ethnicity and poorer socioeconomic status were predictive of greater trauma exposure and symptoms. Results suggest that more inclusive definitions of trauma are important for gender equity, and that ethnic group variation in symptoms is better explained by factors such as differential trauma exposure and economic and social status differences, rather than minority status per se. C1 [Klest, Bridget; Freyd, Jennifer J.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. [Foynes, Melissa Ming] VA Boston Healthcare Syst, Psychol & VA Natl Ctr PTSD, Boston, MA USA. RP Klest, B (reprint author), VA Puget Sound, 1660 South Columbian Way, Seattle, WA 98108 USA. EM bklest@gmail.com FU NIA NIH HHS [R01 AG020048] NR 35 TC 8 Z9 8 U1 0 U2 10 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2013 VL 5 IS 5 BP 409 EP 416 DI 10.1037/a0029336 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 219NY UT WOS:000324514900002 PM 24660048 ER PT J AU MacDonald, HZ Proctor, SP Heeren, T Vasterling, JJ AF MacDonald, Helen Z. Proctor, Susan P. Heeren, Timothy Vasterling, Jennifer J. TI Associations of Postdeployment PTSD Symptoms With Predeployment Symptoms in Iraq-Deployed Army Soldiers SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD symptom clusters; OIF; deployment; longitudinal ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; GULF-WAR VETERANS; PSYCHOLOGICAL DISTRESS; LONGITUDINAL COURSE; MENTAL-HEALTH; TRAUMA; COMORBIDITY; MILITARY; SAMPLE AB Prior to deployment, military personnel may experience a range of symptoms typically associated with posttraumatic stress disorder (PTSD); however, the relationship of specific preexisting symptoms characteristic of PTSD to postdeployment PTSD symptoms is not well understood. This prospective study examined (a) pre- to postdeployment changes in reexperiencing, avoidance, numbing, and hyperarousal symptoms among Iraq-deployed military personnel, and (b) pre- to postdeployment associations among these symptom groupings. Seven-hundred and seventy-four U.S. Army soldiers completed the PTSD Checklist pre- and postdeployment to Iraq. Participants demonstrated increases in reexperiencing, avoidance, and hyperarousal symptom severity but not in severity of numbing symptoms from pre- to postdeployment. Predeployment numbing was positively correlated with all postdeployment symptom clusters, and predeployment hyperarousal was positively correlated with postdeployment hyperarousal, reexperiencing, and numbing. Findings highlight the role of preexisting numbing and hyperarousal symptoms in the evolution of PTSD symptoms following trauma exposure. C1 [MacDonald, Helen Z.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [MacDonald, Helen Z.; Vasterling, Jennifer J.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. [MacDonald, Helen Z.; Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Proctor, Susan P.] US Army Res Inst Environm Med, Mil Performance Div, Natick, MA USA. [MacDonald, Helen Z.; Proctor, Susan P.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Heeren, Timothy] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. RP MacDonald, HZ (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. EM hzm@bu.edu NR 40 TC 5 Z9 5 U1 7 U2 18 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2013 VL 5 IS 5 BP 470 EP 476 DI 10.1037/a0029010 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 219NY UT WOS:000324514900010 ER PT J AU Agboola, SO Ball, M Kvedar, JC Jethwani, K AF Agboola, Stephen O. Ball, Madeleine Kvedar, Joseph C. Jethwani, Kamal TI The future of Connected Health in preventive medicine SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Review ID PERSONALIZED MEDICINE; CANCER AB Over the last decade, Connected Health (CH) has shown great value in the management of chronic disease (CD), but has limited application in preventing these diseases that remain a huge burden to the society. Technological advances have made determination of genetic predisposition to disease possible and have gained wide use in oncology to develop more effective and individualized treatment strategies-Personalized Medicine. There is growing interest in the application of these genetic tests in predicting risk for complex genetic diseases; even, direct-to-consumer tests are increasingly becoming available and affordable. CH has shown great potential in collecting phenotypic data, which can be overlaid on genomic data to deliver a more precise and personalized preventive care that better engages patients. The goal of a CH program that uses genetic data would be to monitor individuals' risk factors and predict the onset of CD. This prediction would be coupled with coaching to delay or prevent the onset of disease. However, the challenge remains that many CDs are due to complex interaction between genes and modifiable environmental risk factors that are still under-studied. C1 [Agboola, Stephen O.; Kvedar, Joseph C.; Jethwani, Kamal] Partners Healthcare, Ctr Connected Hlth, Boston, MA USA. [Agboola, Stephen O.; Kvedar, Joseph C.; Jethwani, Kamal] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Agboola, Stephen O.; Kvedar, Joseph C.; Jethwani, Kamal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ball, Madeleine] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Agboola, SO (reprint author), 25 New Chardon St,Suite 300, Boston, MA 02128 USA. EM sagboola@partners.org NR 17 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD SEP PY 2013 VL 106 IS 9 BP 791 EP 794 DI 10.1093/qjmed/hct088 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 224HS UT WOS:000324874500002 PM 23598385 ER PT J AU White, T Ehrlich, S Ho, BC Manoach, DS Caprihan, A Schulz, SC Andreasen, NC Gollub, RL Calhoun, VD Magnotta, VA AF White, Tonya Ehrlich, Stefan Ho, Beng-Choon Manoach, Dara S. Caprihan, Arvind Schulz, S. Charles Andreasen, Nancy C. Gollub, Randy L. Calhoun, Vince D. Magnotta, Vincent A. TI Spatial Characteristics of White Matter Abnormalities in Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE diffusion tensor imaging; fractional anisotropy; pothole; tract-based spatial statistics ID EARLY-ONSET SCHIZOPHRENIA; DIFFUSION TENSOR; MRI; CONNECTIVITY; DYSFUNCTION; INTEGRITY; DISRUPTION; ANISOTROPY AB There is considerable evidence implicating brain white matter (WM) abnormalities in the pathophysiology of schizophrenia; however, the spatial localization of WM abnormalities reported in the existing studies is heterogeneous. Thus, the goal of this study was to quantify the spatial characteristics of WM abnormalities in schizophrenia. One hundred and fourteen patients with schizophrenia and 138 matched controls participated in this multisite study involving the Universities of Iowa, Minnesota, and New Mexico, and the Massachusetts General Hospital. We measured fractional anisotropy (FA) in brain WM regions extracted using 3 different image-processing algorithms: regions of interest, tract-based spatial statistics, and the pothole approach. We found that FA was significantly lower in patients using each of the 3 image-processing algorithms. The region-of-interest approach showed multiple regions with lower FA in patients with schizophrenia, with overlap at all 4 sites in the corpus callosum and posterior thalamic radiation. The tract-based spatial statistic approach showed (1) global differences in 3 of the 4 cohorts and (2) lower frontal FA at the Iowa site. Finally, the pothole approach showed a significantly greater number of WM potholes in patients compared to controls at each of the 4 sites. In conclusion, the spatial characteristics of WM abnormalities in schizophrenia reflect a combination of a global low-level decrease in FA, suggesting a diffuse process, coupled with widely dispersed focal reductions in FA that vary spatially among individuals (ie, potholes). C1 [White, Tonya] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [White, Tonya] Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Ehrlich, Stefan; Manoach, Dara S.; Gollub, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ehrlich, Stefan] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Dresden, Germany. [Ho, Beng-Choon; Andreasen, Nancy C.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Manoach, Dara S.; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Caprihan, Arvind; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Schulz, S. Charles] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Magnotta, Vincent A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. RP White, T (reprint author), Erasmus MC Sophia, Afdeling Kinder Jeugdpsychiat, Kamer KP 2869,Postbus 2060, NL-3000 CB Rotterdam, Netherlands. EM t.white@erasmusmc.nl RI Ho, Beng-Choon/D-6959-2011; OI Ho, Beng-Choon/0000-0003-3976-1555; Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044 FU National Institute of Mental Health [K08 MH068540, MH060662]; National Institute on Drug Abuse [P2ODA024196]; National Association for Research in Schizophrenia and Affective Disorders (NARSAD); Mind Research Network FX National Institute of Mental Health (K08 MH068540, MH060662); the National Institute on Drug Abuse (P2ODA024196); the National Association for Research in Schizophrenia and Affective Disorders (NARSAD); and the Mind Research Network. NR 52 TC 20 Z9 20 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2013 VL 39 IS 5 BP 1077 EP 1086 DI 10.1093/schbul/sbs106 PG 10 WC Psychiatry SC Psychiatry GA 212HD UT WOS:000323972700020 PM 22987296 ER PT J AU Shore, DE Ruvkun, G AF Shore, David E. Ruvkun, Gary TI A cytoprotective perspective on longevity regulation SO TRENDS IN CELL BIOLOGY LA English DT Review DE cytoprotection; hormesis; detoxification; stress; longevity; aging ID NEMATODE CAENORHABDITIS-ELEGANS; LONG-LIVED MUTANTS; OXIDATIVE STRESS RESISTANCE; CONTROLLING DAUER FORMATION; UNFOLDED PROTEIN RESPONSE; MESSENGER-RNA TRANSLATION; FREE-RADICAL PRODUCTION; LIFE-SPAN EXTENSION; C-ELEGANS; GENE-EXPRESSION AB There are many mechanisms of lifespan extension, including the disruption of insulin/insulin-like growth factor 1 (IGF-1) signaling, metabolism, translation, and feeding. Despite the disparate functions of these pathways, inhibition of each induces responses that buffer stress and damage. Here, emphasizing data from genetic analyses in Caenorhabditis elegans, we explore the effectors and upstream regulatory components of numerous cytoprotective mechanisms activated as major elements of longevity programs, including detoxification, innate immunity, proteostasis, and oxidative stress response. We show that their induction underpins longevity extension across functionally diverse triggers and across species. Intertwined with the evolution of longevity, cytoprotective pathways are coupled to the surveillance of core cellular components, with important implications in normal and aberrant responses to drugs, chemicals, and pathogens. C1 [Shore, David E.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Shore, David E.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIA NIH HHS [R01 AG016636] NR 168 TC 32 Z9 32 U1 0 U2 34 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD SEP PY 2013 VL 23 IS 9 BP 409 EP 420 DI 10.1016/j.tcb.2013.04.007 PG 12 WC Cell Biology SC Cell Biology GA 223GD UT WOS:000324791800001 PM 23726168 ER PT J AU Durante, M Reppingen, N Held, KD AF Durante, Marco Reppingen, Norman Held, Kathryn D. TI Immunologically augmented cancer treatment using modern radiotherapy SO TRENDS IN MOLECULAR MEDICINE LA English DT Review DE immunotherapy; radiotherapy; abscopal effects; combined treatments ID CARBON ION RADIOTHERAPY; IMMUNOGENIC CELL-DEATH; TUMOR-NECROSIS-FACTOR; CD8(+) T-CELLS; NF-KAPPA-B; KINASE INHIBITOR LY2109761; IMAGE-GUIDED RADIOTHERAPY; HEPATOCYTE GROWTH-FACTOR; IONIZING-RADIATION; TGF-BETA AB Radiation oncology has recently seen tremendous technical advances, resulting in increasing cancer cures. However, malignant neoplasias are systemic diseases and may be lethal even with an excellent tumor local control. Immune therapy has grown to a mature approach in oncology, delivering results impossible only a few years ago. Treatment-limiting mechanisms such as the immune suppressive tumor microenvironment are now to a large extent deciphered, allowing for pharmacological intervention. Interestingly, radiation-based treatment effects have been shown to depend to a large degree on the immune system. Applying the recent advances in radiation therapy in conjunction with immune therapy can be a turning point towards the long-standing aim of curing cancer. Only a detailed understanding of the molecular mechanisms can guide the implementation of combined therapy modalities. C1 [Durante, Marco] GSI Helmholtzzentrum Schwerionenforsch, Dept Biophys, Darmstadt, Germany. [Durante, Marco; Reppingen, Norman] Tech Univ Darmstadt, Darmstadt, Germany. [Held, Kathryn D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Durante, M (reprint author), GSI Helmholtzzentrum Schwerionenforsch, Dept Biophys, Darmstadt, Germany. EM M.Durante@gsi.de RI Durante, Marco/K-1315-2014; OI Durante, Marco/0000-0002-4615-553X FU Federal Share of program income earned by Massachusetts General Hospital (MGH) on the National Institutes of Health (NIH) [C06 CA059267] FX We thank the Portfolio "Technologie und Methzin' in the Helmholtz Gemeinschaft for support. Work on radioimmunology at GSI is performed in collaboration with the National Institute for Radiological Sciences (MRS) in Chiba (Japan) and is generously supported by the International Open Laboratory (IOL) initiative. K.D.H. is supported in part by the Federal Share of program income earned by Massachusetts General Hospital (MGH) on the National Institutes of Health (NIH) grant C06 CA059267. NR 209 TC 28 Z9 29 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD SEP PY 2013 VL 19 IS 9 BP 565 EP 582 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 226TJ UT WOS:000325058600007 PM 23831337 ER PT J AU Baker, K AF Baker, Keith TI The Tip of the Iceberg: Improving the Quality of Rank Order Lists for the Match SO ACADEMIC MEDICINE LA English DT Editorial Material AB Many factors limit the ability of resident selection committees to reliably determine which medical student applicants will be top performers in their internship and residency programs. Resident selection committees expend significant time and effort to read applications and then interview and score applicants, all with the goal of creating a rank order list (ROL) for the National Residency Matching Program. Although much of the information used in this process is outside the control of the selection committee, one factor they can control is how they use committee member scores to create the ROL. ROLs are typically generated using the average score assigned by committee members. With this approach, a single harsh faculty member can strongly influence the rank order of applicants if he or she scores only some of the applicants. The author of this commentary discusses the challenges inherent in the creation of ROLs and examines a new approach, described by Ross and Moore in this issue, that can eliminate the problem of biased scoring. ROLs created using this new ROSS-MOORE (Recruitment Outcomes Simulation System-Moore Optimized Ordinal Rank Estimator) approach will better represent the rank ordering of each faculty member of the selection committee. However, ROLs will remain poorly predictive of future performance in internship and residency programs until evaluative data supplied by medical schools are more accurate in predicting which students will become excellent physicians. C1 [Baker, Keith] Harvard Univ, Sch Med, Boston, MA USA. [Baker, Keith] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Baker, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM khbaker@partners.org NR 4 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2013 VL 88 IS 9 BP 1206 EP 1208 DI 10.1097/ACM.0b013e31829ed3eb PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 208AN UT WOS:000323647300017 PM 23887012 ER PT J AU Gallin, EK Bond, E Califf, RM Crowley, WF Davis, P Galbraith, R Reece, EA AF Gallin, Elaine K. Bond, Enriqueta Califf, Robert M. Crowley, William F., Jr. Davis, Pamela Galbraith, Richard Reece, E. Albert TI Forging Stronger Partnerships Between Academic Health Centers and Patient-Driven Organizations SO ACADEMIC MEDICINE LA English DT Article ID HUNTINGTONS-DISEASE; CLINICAL-RESEARCH; LYMPHANGIOLEIOMYOMATOSIS; SAFETY AB In this article, the authors review the unique role that patient-driven organizations, such as patient advocacy groups and voluntary health organizations (PAG/VHOs), play in translational and clinical research. The importance of fostering collaborations between these organizations and U.S. academic health centers (AHCs) is also discussed. Although both the PAG/VHO community and AHCs are heterogeneous, and although not all organizations are well governed or provide independent, well-researched views, there are many outstanding, well-managed, independent PAG/VHOs in the United States whose missions overlap with those of AHCs. The characteristics of effective PAG/VHOs that would serve as excellent partners for AHCs are discussed, and examples are provided regarding their many contributions, which have included advancing research on rare diseases, recruiting patients for clinical trials, and establishing patient registries and biospecimen banks. The authors present feedback obtained from informal discussions with PAG/VHO staff, as well as a survey of a small sample of organizations, that has identified bureaucratic processes, negotiating intellectual property rights, and institutional review board (IRB) delays as the most problematic areas of interactions with AHCs. Actions are suggested for building effective partnerships between the two sectors and the activities that AHCs should undertake to facilitate their interactions with PAG/VHOs including streamlining contract review and IRB processes and finding ways to better align the incentives motivating academic clinical and translational investigators with the goals of PAG/VHOs. This article is one product of the Clinical Research Forum's Partnering with Patient Advocacy Groups Initiative. C1 [Gallin, Elaine K.; Bond, Enriqueta] QE Philanthrop Advisors, Potomac, MD 20854 USA. [Bond, Enriqueta] Burroughs Wellcome Fund, Res Triangle Pk, NC USA. [Califf, Robert M.] Duke Univ, Sch Med, Durham, NC USA. [Califf, Robert M.] Duke Univ, Durham, NC USA. [Califf, Robert M.] Duke Translat Res Inst, Durham, NC USA. [Crowley, William F., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Crowley, William F., Jr.] Harvard Reprod Sci Ctr Excellence, Boston, MA USA. [Crowley, William F., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Davis, Pamela] Med Affairs & Arline & Curtis Garvin Res, Cleveland, OH USA. [Davis, Pamela] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Galbraith, Richard] UVM Ctr Clin & Translat Sci, Burlington, VT USA. [Galbraith, Richard] Case Western Reserve Univ, Sch Med, Burlington, VT USA. [Reece, E. Albert] Univ Maryland, Baltimore, MD 21201 USA. [Reece, E. Albert] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Gallin, EK (reprint author), QE Philanthrop Advisors, 7313 Brookstone Dr, Potomac, MD 20854 USA. EM egallin@gmail.com NR 28 TC 8 Z9 8 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2013 VL 88 IS 9 BP 1220 EP 1224 DI 10.1097/ACM.0b013e31829ed2a7 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 208AN UT WOS:000323647300021 PM 23887007 ER PT J AU Switzer, GE Robinson, GFWB Rubio, DM Fowler, NR Kapoor, WN AF Switzer, Galen E. Robinson, Georgeanna F. W. B. Rubio, Doris M. Fowler, Nicole R. Kapoor, Wishwa N. TI Doctoral Programs to Train Future Leaders in Clinical and Translational Science SO ACADEMIC MEDICINE LA English DT Article ID AWARDS AB Purpose Although the National Institutes of Health (NIH) has made extensive investments in educational programs related to clinical and translational science (CTS), there has been no systematic investigation of the number and characteristics of PhD programs providing training to future leaders in CTS. The authors undertook to determine the number of institutions that, having had received NIH-funded Clinical and Translational Science Awards (CTSAs), currently had or were developing PhD programs in CTS; to examine differences between programs developed before and after CTSA funding; and to provide detailed characteristics of new programs. Method In 2012, CTS program leaders at the 60 CTSA-funded institutions completed a cross-sectional survey focusing on four key domains related to PhD programs in CTS: program development and oversight; students; curriculum and research; and milestones. Results Twenty-two institutions had fully developed PhD programs in CTS, and 268 students were earning PhDs in this new field; 13 institutions were planning PhD programs. New programs were more likely to have fully developed PhD competencies and more likely to include students in medical school, students working only on their PhD, students working on a first doctoral degree, and students working in T1 translational research. They were less likely to include physicians and students working in clinical or T2 research. Conclusions Although CTS PhD programs have similarities, they also vary in their characteristics and management of students. This may be due to diversity in translational science itself or to the relative infancy of CTS as a discipline. C1 [Switzer, Galen E.] Univ Pittsburgh, Pittsburgh, PA USA. [Switzer, Galen E.; Fowler, Nicole R.] Univ Pittsburgh, Dept Med, PhD Program Clin & Translat Sci, Pittsburgh, PA USA. [Switzer, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Robinson, Georgeanna F. W. B.; Rubio, Doris M.] Univ Pittsburgh, Sch Med, Inst Clin Res Educ, Pittsburgh, PA USA. [Rubio, Doris M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Rubio, Doris M.] Univ Pittsburgh, Sch Med, Ctr Data, Ctr Res Hlth, Pittsburgh, PA USA. [Rubio, Doris M.] Univ Pittsburgh, Sch Med, Off Evaluat, Pittsburgh, PA USA. [Rubio, Doris M.] Univ Pittsburgh, Sch Med, Dept Med, Off Lifelong Learning, Pittsburgh, PA 15213 USA. [Kapoor, Wishwa N.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Kapoor, Wishwa N.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Kapoor, Wishwa N.] Univ Pittsburgh, Inst Clin Res Educ, Pittsburgh, PA USA. [Kapoor, Wishwa N.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Kapoor, Wishwa N.] Univ Pittsburgh, RAND Univ Pittsburgh Hlth Inst, Pittsburgh, PA USA. [Kapoor, Wishwa N.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. RP Switzer, GE (reprint author), Iroquois Bldg 502,3600 Forbes Ave, Pittsburgh, PA 15213 USA. EM switzerge@upmc.edu OI Robinson, Georgeanna/0000-0001-6205-2867 FU National Institutes of Health (NIH) [UL1 RR024153, UL1TR000005] FX The project described was supported by the National Institutes of Health (NIH) through grant numbers UL1 RR024153 and UL1TR000005. NR 10 TC 3 Z9 3 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2013 VL 88 IS 9 BP 1332 EP 1339 DI 10.1097/ACM.0b013e31829e7bce PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 208AN UT WOS:000323647300040 PM 23899901 ER PT J AU Robinson, GFWB Switzer, GE Cohen, ED Primack, BA Kapoor, WN Seltzer, DL Bakken, LL Rubio, DM AF Robinson, Georgeanna F. W. B. Switzer, Galen E. Cohen, Elan D. Primack, Brian A. Kapoor, Wishwa N. Seltzer, Deborah L. Bakken, Lori L. Rubio, Doris McGartland TI A Shortened Version of the Clinical Research Appraisal Inventory: CRAI-12 SO ACADEMIC MEDICINE LA English DT Article ID PHYSICIAN-SCIENTISTS; SELF-EFFICACY; CAREER AB Purpose The original Clinical Research Appraisal Inventory (CRAI), which assesses the self-confidence of trainees in performing different aspects of clinical research, comprises 92 items. Completing the lengthy CRAI is time-consuming and represents a considerable burden to respondents, yet the CRAI provides useful data for evaluating research training programs. The purpose of this study is to develop a shortened version of the CRAI and to test its validity and reliability. Method Trainees in clinical research degree and career development programs at the University of Pittsburgh's Institute for Clinical Research Education completed the 92-item CRAI between 2007 and 2012, inclusive. The authors conducted, first, exploratory factor analysis on a training dataset (2007-2010) to reduce the number of items and, then, confirmatory factor analyses on a testing dataset (2011-2012) to test the psychometric properties of the shortened version. Results Of 546 trainees, 394 (72%) provided study data. Exploratory factor analysis revealed six distinct factors, and confirmatory factor analysis identified the two items with the highest loadings per factor, for a total of 12 items. Cronbach alpha for the six new factors ranged from 0.80 to 0.94. Factors in the 12-item CRAI were strongly and significantly associated with factors in the 92-item CRAI; correlations ranged from 0.82 to0.96 (P < .001 for each). Conclusions The 12-item CRAI is faster and less burdensome to complete but retains the strong psychometric properties of the original CRAI. C1 [Robinson, Georgeanna F. W. B.] Univ Pittsburgh, Sch Med, Inst Clin Res Educ, Pittsburgh, PA USA. [Switzer, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Switzer, Galen E.; Primack, Brian A.; Rubio, Doris McGartland] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Cohen, Elan D.; Rubio, Doris McGartland] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care Data Ctr, Pittsburgh, PA USA. [Kapoor, Wishwa N.; Seltzer, Deborah L.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Kapoor, Wishwa N.; Seltzer, Deborah L.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Kapoor, Wishwa N.; Seltzer, Deborah L.; Rubio, Doris McGartland] Univ Pittsburgh, Sch Med, Inst Clin Res Educ, Pittsburgh, PA USA. [Kapoor, Wishwa N.] Univ Pittsburgh, Sch Med, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Bakken, Lori L.] Univ Wisconsin, Sch Human Ecol, Dept Interdisciplinary Studies, Madison, WI USA. RP Robinson, GFWB (reprint author), Inst Clin Res Educ, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM gwrobins@pitt.edu OI Robinson, Georgeanna/0000-0001-6205-2867 FU National Institutes of Health [UL1 RR024153, UL1TR000005] FX The National Institutes of Health supported this study through grant numbers UL1 RR024153 and UL1TR000005. NR 11 TC 2 Z9 2 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD SEP PY 2013 VL 88 IS 9 BP 1340 EP 1345 DI 10.1097/ACM.0b013e31829e75e5 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 208AN UT WOS:000323647300041 PM 23886999 ER PT J AU Roberts, LW Ohayon, M Coverdale, J Goldsmith, M Beresin, EV Louie, AK Tait, GR Balon, R AF Roberts, Laura Weiss Ohayon, Maurice Coverdale, John Goldsmith, Michelle Beresin, Eugene V. Louie, Alan K. Tait, Glendon R. Balon, Richard TI Strengthening Psychiatry's Numbers SO ACADEMIC PSYCHIATRY LA English DT Editorial Material ID MEDICAL-STUDENTS; RECRUITMENT; DEPRESSION; MANAGEMENT; CHALLENGE; CAREER C1 [Roberts, Laura Weiss; Goldsmith, Michelle; Louie, Alan K.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Ohayon, Maurice] Stanford Univ, Dept Psychiat, Sleep Epidemiol Res Ctr, Stanford, CA 94305 USA. [Beresin, Eugene V.] Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. [Beresin, Eugene V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Coverdale, John] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Balon, Richard] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. [Tait, Glendon R.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. RP Roberts, LW (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. EM RobertsL@stanford.edu NR 21 TC 4 Z9 4 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SEP-OCT PY 2013 VL 37 IS 5 BP 293 EP 296 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 211NX UT WOS:000323916200001 PM 24026364 ER PT J AU Johnson, JM Stern, TA AF Johnson, Justin M. Stern, Theodore A. TI Preparing Psychiatrists for Leadership Roles in Healthcare SO ACADEMIC PSYCHIATRY LA English DT Editorial Material ID SPECIALTY CHOICE; PERSPECTIVE; STUDENTS C1 [Johnson, Justin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, McLean Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Consultat Serv, Cambridge, MA 02138 USA. RP Johnson, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM jjohnson54@partners.org NR 16 TC 4 Z9 4 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SEP-OCT PY 2013 VL 37 IS 5 BP 297 EP 300 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 211NX UT WOS:000323916200002 PM 24026366 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO ADVANCES IN PHYSIOLOGY EDUCATION LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Dept Med, Med Coll Wisconsin, Milwaukee, WI USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Dept Surg, Med Coll Wisconsin, Milwaukee, WI USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Dept Physiol, Med Coll Wisconsin, Milwaukee, WI USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, Endocrine Res Lab, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 1 Z9 1 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1043-4046 J9 ADV PHYSIOL EDUC JI Adv. Physiol. Educ. PD SEP PY 2013 VL 37 IS 3 BP 211 EP 212 DI 10.1152/advan.00046.2013 PG 2 WC Education, Scientific Disciplines; Physiology SC Education & Educational Research; Physiology GA 216VB UT WOS:000324312100001 PM 24022765 ER PT J AU Bagai, A White, JA Lokhnygina, Y Giugliano, RP Van de Werf, F Montalescot, G Armstrong, PW Tricoci, P Gibson, CM Califf, RM Harrington, RA Newby, LK AF Bagai, Akshay White, Jennifer A. Lokhnygina, Yuliya Giugliano, Robert P. Van de Werf, Frans Montalescot, Gilles Armstrong, Paul W. Tricoci, Pierluigi Gibson, C. Michael Califf, Robert M. Harrington, Robert A. Newby, L. Kristin TI Routine early eptifibatide versus delayed provisional use at percutaneous coronary intervention in high-risk non-ST-segment elevation acute coronary syndromes patients: An analysis from the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome trial SO AMERICAN HEART JOURNAL LA English DT Article ID PLACEBO-CONTROLLED TRIAL; UPSTREAM TIROFIBAN; CLINICAL-OUTCOMES; ANGIOPLASTY; ABCIXIMAB; BENEFIT AB Aims In the EARLY ACS trial, routine early eptifibatide was not superior to delayed provisional use at percutaneous coronary intervention (PCI); however, among PCI-treated patients, numerically fewer ischemic end points occurred in the upstream eptifibatide group. We sought to further explore this finding using methods for examination of treatment effect in this postrandomization subgroup. Methods and results Of 9,406 patients in the EARLY ACS primary analysis cohort, 9,166 (97.4%) underwent coronary angiography. We used Cox proportional hazards regression modeling, with PCI as a time-dependent covariate, to examine the effect of routine early versus delayed provisional eptifibatide among 5,541 patients undergoing PCI and to explore the interaction between treatment with PCI and randomized treatment strategy. After multivariable adjustment, compared with delayed provisional use, routine early eptifibatide was associated with lower rate of 30-day death or myocardial infarction (MI) after PCI (hazard ratio [HR] 0.80, 95% CI 0.68-0.95) but not with medical management (HR 0.97, 95% CI 0.74-1.29); PCI x randomized treatment interaction term P = .24. Excluding PCI-related MI, the adjusted HR for 30-day death or MI for routine early eptifibatide versus delayed provisional use was 0.80 (95% CI 0.60-1.08) for post-PCI treatment and 1.01 (95% CI 0.79-1.34) for medical management; PCI x randomized treatment interaction term P =.28. Conclusions Consistent with previous literature, upstream treatment with eptifibatide was associated with improved outcomes in high-risk non-ST-segment elevation acute coronary syndrome patients treated with PCI; however, a nonsignificant interaction term precludes a definite conclusion. C1 [Bagai, Akshay; White, Jennifer A.; Lokhnygina, Yuliya; Tricoci, Pierluigi; Newby, L. Kristin] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Giugliano, Robert P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Giugliano, Robert P.] TIMI Study Grp, Boston, MA USA. [Van de Werf, Frans] Katholieke Univ Leuven Hosp, Louvain, Belgium. [Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. [Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada. [Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Hosp Deaconess Med Ctr, Boston, MA USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. [Harrington, Robert A.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. RP Newby, LK (reprint author), Duke Box 3213,2400 Pratt St,Room 7022,Terrace Lev, Durham, NC 27705 USA. EM newby001@mc.duke.edu FU Merck Co, Inc; Merck & Co, 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 & Co, Inc, Whitehouse Station, NJ, USA. NR 17 TC 0 Z9 1 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2013 VL 166 IS 3 BP 466 EP + DI 10.1016/j.ahj.2013.05.019 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 214UZ UT WOS:000324163600020 PM 24016495 ER PT J AU Block, GA Ix, JH Ketteler, M Martin, KJ Thadhani, RI Tonelli, M Wolf, M Juppner, H Hruska, K Wheeler, DC AF Block, Geoffrey A. Ix, Joachim H. Ketteler, Markus Martin, Kevin J. Thadhani, Ravi I. Tonelli, Marcello Wolf, Myles Jueppner, Harald Hruska, Keith Wheeler, David C. TI Phosphate Homeostasis in CKD: Report of a Scientific Symposium Sponsored by the National Kidney Foundation SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Phosphate; chronic kidney disease; diet; food labeling; chronic kidney disease-mineral and bone disorder (CKD-MBD) ID GROWTH-FACTOR 23; VITAMIN-D METABOLISM; STAGE RENAL-DISEASE; DIETARY PHOSPHORUS INTAKE; LEFT-VENTRICULAR MASS; SERUM PHOSPHORUS; MINERAL METABOLISM; CARDIOVASCULAR-DISEASE; SECONDARY HYPERPARATHYROIDISM; HYPOPHOSPHATEMIC RICKETS AB Chronic kidney disease (CKD)-mineral and bone disorder is associated with diverse metabolic and endocrine disturbances that ultimately may contribute to further loss of kidney function, bone demineralization, and fatal or nonfatal cardiovascular events. Recent insights into the pathophysiology of the events that unfold during the development of this disorder suggest that disturbances in phosphate metabolism are pivotal. The consequences of abnormal phosphate homeostasis are evident at estimated glomerular filtration rates <70 mL/min/1.73m(2), long before serum phosphate levels increase. Healthy individuals with blood phosphate levels in the top quartile of the normal range have an increased risk of developing CKD, reaching end-stage renal disease, and experiencing cardiovascular events. Substantial public health consequences may be related to increased dietary phosphorus exposure from additives that contain phosphate in the food supply and from modest increases in serum phosphate levels; however, it remains to be established whether interventions aimed at these targets can impact on the development of adverse clinical outcomes. Current approaches involving dietary intervention and intestinal phosphate binders are based on principles and assumptions that need to be examined more rigorously. Compelling animal, observational, and clinical data indicate that interventions directed at lowering phosphate exposure and serum phosphate levels should be subject to rigorous clinical trials that use appropriate placebo comparators and focus on key clinical outcomes, such as cardiovascular events, progression of CKD, fractures, quality of life, and mortality. (C) 2013 by the National Kidney Foundation, Inc. C1 [Block, Geoffrey A.] Denver Nephrologists, Denver, CO USA. [Ix, Joachim H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Ketteler, Markus] Klinikum Coburg Hosp, Coburg, Germany. [Martin, Kevin J.] St Louis Univ, St Louis, MO 63103 USA. [Thadhani, Ravi I.; Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thadhani, Ravi I.; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tonelli, Marcello] Univ Alberta, Edmonton, AB, Canada. [Wolf, Myles] Univ Miami Miller Sch Med, Miami, FL USA. [Hruska, Keith] Washington Univ, St Louis, MO USA. [Wheeler, David C.] UCL, London, England. RP Block, GA (reprint author), Denver Nephrologists PC, 130 Rampart Way, Denver, CO 80230 USA. EM gablock@dnresearch.org RI Tonelli, Marcello/B-3028-2009 FU CMD Pharma; Cytochroma; Sanofi; Vifor FX CM&D Pharma, Cytochroma, Sanofi, and Vifor provided grants to the National Kidney Foundation to support the conference. NR 99 TC 31 Z9 31 U1 1 U2 34 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2013 VL 62 IS 3 BP 457 EP 473 DI 10.1053/j.ajkd.2013.03.042 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA 212ZZ UT WOS:000324023700008 PM 23763855 ER PT J AU Campbell, KH Huang, ES Dale, W Parker, MM John, PM Young, BA Moffet, HH Laiteerapong, N Karter, AJ AF Campbell, Kellie Hunter Huang, Elbert S. Dale, William Parker, Melissa M. John, Priya M. Young, Bessie A. Moffet, Howard H. Laiteerapong, Neda Karter, Andrew J. TI Association Between Estimated GFR, Health-Related Quality of Life, and Depression Among Older Adults With Diabetes: The Diabetes and Aging Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Aging; chronic kidney disease (CKD); depression; quality of life ID CHRONIC KIDNEY-DISEASE; NORTHERN CALIFORNIA DISTANCE; GLOMERULAR-FILTRATION-RATE; RENAL-DISEASE; DIALYSIS; HOSPITALIZATION; INITIATION; EQUATION; PROFILE; COHORT AB Background: Although chronic kidney disease (CKD) is a highly prevalent condition among older adults with diabetes, the associations between health-related quality of life (HRQoL) and severity of CKD in this population are not well understood. The objective of this study was to assess HRQoL and depressive symptoms across estimated glomerular filtration rate (eGFR) stages. Study Design: Cross-sectional. Setting & Participants: 5,805 members of Kaiser Permanente Northern California, 60 years or older with diabetes, from the 2005-2006 Diabetes Study of Northern California (DISTANCE) survey. Predictor: eGFR categories were defined as >= 90 (referent category), 75-89, 60-74, 45-59, 30-44, or <= 29 mL/min/1.73 m(2). Outcomes: HRQoL was measured using the modified Short Form -8 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Depressive symptoms were measured using the Patient Health Questionnaire -8. Results: In unadjusted linear regression analyses, physical (PCS) and mental (MCS) HRQoL scores were significantly lower with worsening eGFR level. However, after adjustment for sociodemographics, diabetes duration, obesity, and cardiovascular comorbid conditions and taking into account interactions with proteinuria, none of the eGFR categories was significantly or substantively associated with PCS or MCS score. In both unadjusted and adjusted analyses, higher risk of depressive symptoms was observed in respondents with eGFR <= 29 mL/min/1.73 m(2) (relative risk, 2.02; 95% CI, 1.10-3.71; P < 0.05) compared with the referent group. However, this eGFR-depression relationship was no longer significant after adjusting for hemoglobin level. Limitations: Participants are part of a single health care delivery system. Conclusions: Our findings suggest the need for greater attention to and potential interventions for depression in patients with reduced eGFR. (C) 2013 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Campbell, Kellie Hunter; Huang, Elbert S.; Dale, William; John, Priya M.; Laiteerapong, Neda] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Parker, Melissa M.; Moffet, Howard H.; Karter, Andrew J.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Young, Bessie A.] Univ Washington, Div Nephrol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Young, Bessie A.] Kidney Res Inst, Seattle, WA USA. RP Campbell, KH (reprint author), Univ Chicago, Sect Geriatr & Palliat Med, 5841 S Maryland Ave,MC 6098, Chicago, IL 60637 USA. EM kcampbel@medicine.bsd.uchicago.edu FU T. Franklin Williams Scholars Award; Atlantic Philanthropies, Inc; American Geriatrics Society Foundation for Health in Aging; John A. Hartford Foundation; Association of Specialty Professors; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK081796, R01DK080726, R01DK65664]; Centers for Diabetes Translation Research at Kaiser Permanente; University of California, San Francisco [P30 DK092924]; University of Chicago [P30 DK092949]; VA Puget Sound Health Care System, Seattle, WA; National Institutes of Health, NIDDK [DK079745] FX Dr Campbell is supported by a T. Franklin Williams Scholars Award. Funding was provided by Atlantic Philanthropies, Inc; the American Geriatrics Society Foundation for Health in Aging; the John A. Hartford Foundation; and the Association of Specialty Professors. The Diabetes and Aging Study was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; grants R01DK081796, R01DK080726, and R01DK65664). Investigators also were supported by the Centers for Diabetes Translation Research at Kaiser Permanente and University of California, San Francisco (P30 DK092924) and the University of Chicago (P30 DK092949). The sponsors played no role in the design or interpretation of the study. Dr Young's contribution is supported by resources from the VA Puget Sound Health Care System, Seattle, WA, and by the National Institutes of Health, NIDDK (DK079745). None of the mentioned funders had input into the content of this manuscript and did not report any potential conflicts of interest relevant to this article. NR 36 TC 4 Z9 4 U1 3 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2013 VL 62 IS 3 BP 541 EP 548 DI 10.1053/j.ajkd.2013.03.039 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 212ZZ UT WOS:000324023700015 PM 23746376 ER PT J AU Shlipak, MG Mattes, MD Peralta, CA AF Shlipak, Michael G. Mattes, Monica D. Peralta, Carmen A. TI Update on Cystatin C: Incorporation Into Clinical Practice SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE Cystatin C; glomerular filtration rate (GFR) estimation; chronic kidney disease ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; SERUM CREATININE; FUNCTION DECLINE; ELDERLY PERSONS; OLDER-ADULTS; RISK-FACTOR; US ADULTS; ALL-CAUSE AB Kidney function monitoring using creatinine-based glomerular filtration rate estimation is a routine part of clinical practice. Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease. In this review and update, we summarize the overall literature on cystatin C, critically evaluate recent high-impact studies, highlight the role of cystatin C in recent kidney disease guidelines, and suggest a practical approach for clinicians to incorporate cystatin C into practice. We conclude by addressing frequently asked questions related to implementing cystatin C use in a clinical setting. (C) 2013 by the National Kidney Foundation, Inc. C1 [Shlipak, Michael G.; Mattes, Monica D.; Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.; Mattes, Monica D.; Peralta, Carmen A.] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Vet Affairs Med Ctr 111A1, 4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU National Institute of Health (NIH)/National Institute on Aging [5R01AG034853-03, 5R01AG027002-06]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK087961-01A1, K23 DK082793] FX Dr Shlipak was supported by National Institute of Health (NIH)/National Institute on Aging grants 5R01AG034853-03 and 5R01AG027002-06, and NIH/National Institute of Diabetes and Digestive and Kidney Diseases grant 1R01DK087961-01A1. Dr Peralta was supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK082793. NR 52 TC 45 Z9 48 U1 3 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2013 VL 62 IS 3 BP 595 EP 603 DI 10.1053/j.ajkd.2013.03.027 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 212ZZ UT WOS:000324023700022 PM 23701892 ER PT J AU Baxter, SL Pistilli, M Pujari, SS Liesegang, TL Suhler, EB Thorne, JE Foster, CS Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Kempen, JH AF Baxter, Sally L. Pistilli, Maxwell Pujari, Siddharth S. Liesegang, Teresa L. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Kempen, John H. TI Risk of Choroidal Neovascularization among the Uveitides SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PUNCTATE INNER CHOROIDOPATHY; INTRAVITREAL BEVACIZUMAB; MULTIFOCAL CHOROIDITIS; REGRESSION-ANALYSIS; DISEASES; VEGF; COMPLICATIONS; NOMENCLATURE; PANUVEITIS; SECONDARY AB PURPOSE: To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in uveitis cases. DESIGN: Retrospective cohort study. METHODS: Standardized medical record review at 5 tertiary centers. RESULTS: Among 15 137 uveitic eyes (8868 patients), CNV was rare in the cases of anterior or intermediate uveitis. Among the 4041 eyes (2307 patients) with posterior uveitis or panuveitis, 81(2.0%) had CNV at presentation. Risk factors included posterior uveitis in general and specific uveitis syndromes affecting the outer retina retinal pigment epithelium choroid interface. Among the 2364 eyes (1357 patients) with posterior uveitis or panuveitis and free of CNV at the time of cohort entry, the cumulative 2-year incidence of CNV was 2.7% (95% confidence interval [CI], 1.8% to 3.5%). Risk factors for incident CNV included currently active inflammation (adjusted hazard ratio [aHR], 2.13; 95% CI, 1.26 to 3.60), preretinal neovascularization (aHR, 3.19; 95% CI, 1.30 to 7.80), and prior diagnosis of CNV in the contralateral eye (aHR, 5.79; 95% CI, 2.77 to 12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada syndrome (aHR, 3.37; 95% CI, 1.52 to 7.46) and punctate inner choroiditis (aHR, 8.67; 95% CI, 2.83 to 26.54). Incident CNV was associated with a 2-line loss of visual acuity (+0.19 logarithm of the minimal angle of resolution units; 95% CI, 0.079 to 0.29) from the preceding visit. CONCLUSIONS: CNV is an uncommon complication Of uveitis associated with visual impairment that occurs more commonly in forms affecting the outer retina retinal pigment epithelium choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate. ((C) 2013 by Elsevier Inc. All rights reserved.) C1 [Baxter, Sally L.; Kempen, John H.] Univ Penn, Perelman Sch Med, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Pistilli, Maxwell; Kempen, John H.] Univ Penn, Perelman Sch Med, Ctr Prevent Ophthalmol & Biostat, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Pujari, Siddharth S.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Pujari, Siddharth S.] Vasan Eye Care Hosp, Belgaum, Karnataka, India. [Liesegang, Teresa L.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Levy-Clarke, Grace A.] Johnson & Johnson, New Brunswick, NJ USA. [Rosenbaum, James T.] Legacy Hlth Syst, Devers Eye Inst, Portland, OR USA. [Kempen, John H.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Pistilli, Maxwell/0000-0002-4266-4150 FU Research to Prevent Blindness, Inc, New York, New York; Paul and Evanina Mackall Foundation; National Eye Institute; Department of Veterans' Affairs FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST and the following were reported. Jennifer E. Thome serves a consultant for Allergan and XOMA. C. Stephen Foster serves as a lecturer for Alcon, Inspire, Ista, and Centocor; as a Consultant for Sirion; as a consultant and lecturer for Allergan and Bausch & Lomb; and as an equity owner for EyeGate. Douglas A. Jabs serves a consultant for Abbott Laboratories, Alcon Laboratories, Allergan Pharmaceutical Corporation, Corcept Therapeutics, Genentech, Genzyme Corporation, GlaxoSmith Kline, and Roche Pharmaceuticals and is a member of the Data and Safety Monitoring Board for Applied Genetic Technologies Corporation and Novartis Pharmaceutical Corporation. Grace A. Levy-Clarke is employed by Johnson & Johnson Vision Care. James T. Rosenbaum serves or has served as a consultant for Abbott Laboratories, Amgen, Allergan, Genentech, Novartis, and UCB and has been involved in clinical trials for Abbott Laboratories, Genentech, Lux Biosciences, and Eyegate Pharma. John H. Kempen serves or has served as a consultant for Alcon, Allergan, Can-Fite, Clearside, Lux Biosciences, Sanofi-Pasteur, and Xoma. Supported primarily by Grant EY014943 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland (J.H.K.). Additional support was provided by Research to Prevent Blindness, Inc, New York, New York, and the Paul and Evanina Mackall Foundation. Dr Kempen was a Research to Prevent Blindness James S Adams Special Scholar Award recipient, Dr Thome was a Research to Prevent Blindness Harrington Special Scholar Award recipient, and Drs Jabs and Rosenbaum were Research to Prevent Blindness Senior Scientific Investigator Award recipients during the course of the study. Dr Levy-Clarke was previously supported by and Dr Nussenblatt continues to be supported by intramural funds from the National Eye Institute. Dr Suhler receives support from the Department of Veterans' Affairs. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of this manuscript. Involved in Design and conduct of study (S.L.B., M.P., J.H.K.); Collection, management, analysis, and interpretation of data (all authors); Preparation of manuscript (S.L.B., M.P., J.H.K.); and review and approval of manuscript (all authors). NR 28 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2013 VL 156 IS 3 BP 468 EP 477 DI 10.1016/j.ajo.2013.04.040 PG 10 WC Ophthalmology SC Ophthalmology GA 214RM UT WOS:000324153500009 PM 23795984 ER PT J AU Sethi, RV Sethi, RKV Herr, MW Deschler, DG AF Sethi, Roshan V. Sethi, Rosh K. V. Herr, Marc W. Deschler, Daniel G. TI Malignant head and neck paragangliomas: Treatment efficacy and prognostic indicators SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID DATA-BASE REPORT; BODY TUMOR; CANCER AB Purpose: Malignant head and neck paragangliomas (MHNPs) are rare and occur in 6%-19% of all HNPs. We sought to identify predictors of survival and compare efficacy of treatment modalities to inform management of this rare disease. Materials and methods: We performed a retrospective cohort study of MHNP cases in the National Cancer Institute Surveillance Epidemiology and End Results database (SEER) from 1973 to 2009. We identified 86 patients with MHNP who had documented regional or distant tumor spread with a median follow-up of 74 months. We used Cox proportional hazard models to assess the significance of demographic factors and treatment on five-year overall survival. Results: The most common treatment was surgery alone (36.0 %), followed by surgery with adjuvant radiation (33.7%). Five-year overall survival was 88.1% for surgery alone and 66.5% for adjuvant radiation (p = 0.2251). In univariate analysis, regional (vs. distant) spread (HR 0.23, p < 0.0001), surgery alone (HR 0.29, p < 0.0001) and primary site in the carotid body (HR 0.32, p = 0.006) conferred significant survival advantage whereas age > 50 (HR 4.04, p < 0.0001) worsened survival. Regional (vs. distant) spread (HR 0.42, p = 0.046) and age > 50 (HR 2.98, p = 0.005) remained significant in multivariate analysis. In patients with regional-only disease, five-year overall survival was 95.4% for surgery alone compared to 75.6% for surgery with radiation (p = 0.1055). Conclusions: This is the largest and most contemporary series of MHNP patients. Age and tumor stage are significant factors in predicting survival. Surgical resection significantly improves survival outcomes. From this analysis, the value of adjuvant radiation is not clear. Published by Elsevier Inc. C1 [Sethi, Roshan V.; Sethi, Rosh K. V.; Deschler, Daniel G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Herr, Marc W.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Head & Neck Surg, Boston, MA 02114 USA. RP Herr, MW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Div Head & Neck Surg, Boston, MA 02114 USA. EM marc_herr@meei.harvard.edu NR 18 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD SEP-OCT PY 2013 VL 34 IS 5 BP 431 EP 438 DI 10.1016/j.amjoto.2013.03.010 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 214QC UT WOS:000324149400013 PM 23642313 ER PT J AU Busaba, NY AF Busaba, Nicolas Y. TI The impact of a patient's age on the clinical presentation of inflammatory paranasal sinus disease SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID ENDOSCOPIC ENDONASAL SURGERY; RECURRING RHINOSINUSITIS AB Objective: To determine the change in the clinical presentation of inflammatory paranasal sinus disease as a function of a patient's age. Study Design and Methods: This is a prospective study of 514 adult patients who presented with inflammatory paranasal sinus disease. The patients were divided into three age groups: group 1 (age: 18-39 years; n = 203), group 2 (age: 40-59 years; n = 213) and group 3 (age greater than 60 years; n = 98). The following data were collected: presenting symptoms, co-morbidities, nasal endoscopy and CT findings, diagnosis, and the outcome of endoscopic sinus surgery (ESS). Statistical analysis was performed using chi-square test, with statistical significance set at p < 0.05. Results: Among the presenting symptoms, facial pain and rhinorrhea were most common in group 1 (p < 0.05), while dysosmia was most common in group 3 (p < 0.05). Environmental allergy, but not asthma, was more prevalent in groups 1 and 2 (p < 0.05). Anatomic abnormalities that obstructed the ostiomeatal unit (OMU) were more common in groups 1 and 2 (p < 0.05). Chronic rhinosinusitis (CRS) without polyposis was the most common diagnosis in group 1 and CRS with polyposis was the most common diagnosis in groups 2 and 3 (p < 0.05). Patients in group 1 reported higher rate of improvement in olfactory function while patients in group 3 reported higher rate of improvement in rhinorrhea following ESS (p < 0.05). Conclusions: Patients in the 18-39-year age group and diagnosed with CRS are more likely to present with facial pain, suffer from environmental allergy, have anatomic abnormalities in the OMU region, and report improvement in their olfaction following ESS. Patients who are 60 years or older are more likely to present with dysosmia, be diagnosed with CRS with nasal polyposis, and report improvement in rhinorrhea following surgery. Published by Elsevier Inc. C1 [Busaba, Nicolas Y.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Busaba, Nicolas Y.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM nicolas_busaba@meei.harvard.edu NR 17 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD SEP-OCT PY 2013 VL 34 IS 5 BP 449 EP 453 DI 10.1016/j.amjoto.2013.03.013 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 214QC UT WOS:000324149400016 PM 23702318 ER PT J AU Khazim, K Gorin, Y Cavaglieri, RC Abboud, HE Fanti, P AF Khazim, Khaled Gorin, Yves Cavaglieri, Rita Cassia Abboud, Hanna E. Fanti, Paolo TI The antioxidant silybin prevents high glucose-induced oxidative stress and podocyte injury in vitro and in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE albuminuria; apoptosis; diabetic nephropathy; NADPH oxidase; phytochemicals ID TYPE-2 DIABETIC-NEPHROPATHY; NADPH OXIDASE ACTIVITY; STAGE RENAL-DISEASE; INDUCED NEPHROTOXICITY; SUPEROXIDE-PRODUCTION; SIGNALING PATHWAYS; OVERT NEPHROPATHY; KIDNEY-DISEASE; SILIBININ; SILYMARIN AB Podocyte injury, a major contributor to the pathogenesis of diabetic nephropathy, is caused at least in part by the excessive generation of reactive oxygen species (ROS). Overproduction of superoxide by the NADPH oxidase isoform Nox4 plays an important role in podocyte injury. The plant extract silymarin is attributed antioxidant and antiproteinuric effects in humans and in animal models of diabetic nephropathy. We investigated the effect of silybin, the active constituent of silymarin, in cultures of mouse podocytes and in the OVE26 mouse, a model of type 1 diabetes mellitus and diabetic nephropathy. Exposure of podocytes to high glucose (HG) increased 60% the intracellular superoxide production, 90% the NADPH oxidase activity, 100% the Nox4 expression, and 150% the number of apoptotic cells, effects that were completely blocked by 10 mu M silybin. These in vitro observations were confirmed by similar in vivo findings. The kidney cortex of vehicle-treated control OVE26 mice displayed greater Nox4 expression and twice as much superoxide production than cortex of silybin-treated mice. The glomeruli of control OVE26 mice displayed 35% podocyte drop out that was not present in the silybin-treated mice. Finally, the OVE26 mice experienced 54% more pronounced albuminuria than the silybin-treated animals. In conclusion, this study demonstrates a protective effect of silybin against HG-induced podocyte injury and extends this finding to an animal model of diabetic nephropathy. C1 [Abboud, Hanna E.; Fanti, Paolo] Audie L Murphy Mem Hosp Div, South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Khazim, Khaled; Gorin, Yves; Cavaglieri, Rita Cassia; Abboud, Hanna E.; Fanti, Paolo] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Khazim, Khaled] Western Galilee Hosp, Nephrol & Hypertens Unit, Nahariyya, Israel. RP Fanti, P (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM fanti@uthscsa.edu FU National Center for Complementary and Alternative Medicine [AT-004490]; Merit Review Grant [1I01CX000264]; Juvenile Diabetes Research Foundation Multiproject Grants; National Institute of Diabetes and Digestive and Kidney Diseases [RO1 DK 079996]; American Physicians Fellowship for Medicine in Israel FX This work was supported in part through National Center for Complementary and Alternative Medicine Grant AT-004490 (P. Fanti), Merit Review Grant 1I01CX000264 (P. Fanti), Juvenile Diabetes Research Foundation Multiproject Grants (Y. Gorin and H. E. Abboud), National Institute of Diabetes and Digestive and Kidney Diseases Grant RO1 DK 079996 (Y. Gorin), and American Physicians Fellowship for Medicine in Israel (K. Khazim). NR 63 TC 27 Z9 29 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP PY 2013 VL 305 IS 5 BP F691 EP F700 DI 10.1152/ajprenal.00028.2013 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 214AA UT WOS:000324101000011 PM 23804455 ER PT J AU Friedman, MJ AF Friedman, Matthew J. TI Toward Rational Pharmacotherapy for Posttraumatic Stress Disorder: Reprise SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 [Friedman, Matthew J.] Geisel Sch Med Dartmouth, US Dept Vet Affairs, Natl Ctr PTSD, Hanover, NH 03755 USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol, Hanover, NH USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Toxicol, Hanover, NH USA. RP Friedman, MJ (reprint author), Geisel Sch Med Dartmouth, US Dept Vet Affairs, Natl Ctr PTSD, Hanover, NH 03755 USA. EM matthew.j.friedman@dartmouth.edu NR 10 TC 4 Z9 4 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2013 VL 170 IS 9 BP 944 EP 946 DI 10.1176/appi.ajp.2013.13060768 PG 3 WC Psychiatry SC Psychiatry GA 212VK UT WOS:000324010700003 PM 24030605 ER PT J AU Ticlea, AN Bajor, LA Osser, DN AF Ticlea, Ana Nectara Bajor, Laura A. Osser, David N. TI Addressing Sleep Impairment in Treatment Guidelines for PTSD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter ID POSTTRAUMATIC-STRESS-DISORDER C1 [Ticlea, Ana Nectara; Bajor, Laura A.; Osser, David N.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02401 USA. RP Ticlea, AN (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02401 USA. NR 7 TC 2 Z9 2 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2013 VL 170 IS 9 BP 1059 EP 1059 DI 10.1176/appi.ajp.2013.13050641 PG 1 WC Psychiatry SC Psychiatry GA 212VK UT WOS:000324010700019 PM 24030614 ER PT J AU Wortzel, HS AF Wortzel, Hal S. TI Clinical Manual of Neuropsychiatry SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Book Review C1 [Wortzel, Hal S.] Denver VA Med Ctr, Educ & Clin Ctr, VISN Mental Illness Res 19, Denver, CO USA. [Wortzel, Hal S.] Univ Colorado, Sch Med, Denver, CO USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2013 VL 170 IS 9 BP 1063 EP 1064 DI 10.1176/appi.ajp.2013.13020193 PG 2 WC Psychiatry SC Psychiatry GA 212VK UT WOS:000324010700023 ER PT J AU Weathington, NM Sznajder, JI Mallampalli, RK AF Weathington, Nathaniel M. Sznajder, Jacob I. Mallampalli, Rama K. TI The Emerging Role of the Ubiquitin Proteasome in Pulmonary Biology and Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE ubiquitin; proteasome; pulmonary disease; drug development; E3 ligase ID SURFACTANT PROTEIN-C; TRANSMEMBRANE CONDUCTANCE REGULATOR; ACUTE LUNG INJURY; NF-KAPPA-B; F-BOX PROTEINS; ALLOSTERIC INHIBITOR; MITOTIC ARREST; BETA-TRCP; DEGRADATION; LIGASE AB Derangements in normal cellular homeostasis at the protein level can cause or be the consequence of initiation and progression of pulmonary diseases related to genotype, infection, injury, smoking, toxin exposure, or neoplasm. We discuss one of the fundamental mechanisms of protein homeostasis, the ubiquitin proteasome system (UPS), as it relates to lung disease. The UPS effects selective degradation of ubiquitinated target proteins via ubiquitin ligase activity. Important pathobiological mechanisms relating to the UPS and lung disease have been the focus of research, with inappropriate cellular proteolysis now a validated therapeutic target. We review the contributions of this system in various lung diseases, and discuss the exciting area of UPS-targeting drug development for pulmonary disease. C1 [Weathington, Nathaniel M.; Mallampalli, Rama K.] Univ Pittsburgh, Acute Lung Injury Ctr Excellence Pulm Allergy & C, Dept Med, Pittsburgh, PA 15213 USA. [Sznajder, Jacob I.] Northwestern Univ, Chicago, IL 60611 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Dept Cell Biol & Physiol, Pittsburgh, PA USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, UPMC Montefiore, Dept Med, NW 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; U.S. Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174, HL-R37-48129, HL-PO1-71643]; Department of Veterans Affairs, Veterans Health Administration, VA Pittsburgh Healthcare System FX The authors thank Bill Chen and Yutong Zhao for careful review of this manuscript. This material is based on work supported, in part, by the U.S. 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 U.S. Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376, and HL098174 (to R. K. M.) and HL-R37-48129 and HL-PO1-71643 (to J.I.S.). N.M.W. is supported by a research fellowship through the U.S. Department of Veterans Affairs, Veterans Health Administration, VA Pittsburgh Healthcare System. NR 72 TC 13 Z9 14 U1 0 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2013 VL 188 IS 5 BP 530 EP 537 DI 10.1164/rccm.201304-0754PP PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 214BU UT WOS:000324106200007 PM 23713962 ER PT J AU Shah, FA Pike, F Alvarez, K Angus, D Newman, AB Lopez, O Tate, J Kapur, V Wilsdon, A Krishnan, JA Hansel, N Au, D Avdalovic, M Fan, VS Barr, G Yende, S AF Shah, Faraaz Ali Pike, Francis Alvarez, Karina Angus, Derek Newman, Anne B. Lopez, Oscar Tate, Judith Kapur, Vishesh Wilsdon, Anthony Krishnan, Jerry A. Hansel, Nadia Au, David Avdalovic, Mark Fan, Vincent S. Barr, Graham Yende, Sachin TI Bidirectional Relationship between Cognitive Function and Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pneumonia; dementia; cognitive function ID RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; LONG-TERM MORTALITY; INFLAMMATORY MARKERS; CARDIOVASCULAR HEALTH; CRITICAL ILLNESS; GLOBAL BURDEN; UNITED-STATES; SEVERE SEPSIS; OLDER-PEOPLE AB Rationale: Relationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems. Objectives: To determine bidirectional relationships between cognition and pneumonia. Methods: We conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate. Measurements and Main Results: Of the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia( proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with [GRAPHICS] and without pneumonia, respectively; P<0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (beta = -0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62-3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections. Conclusions: A bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence. C1 [Shah, Faraaz Ali] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA. [Pike, Francis; Alvarez, Karina; Angus, Derek; Tate, Judith; Yende, Sachin] Univ Pittsburgh, Clin Res Invest & Syst Modeling Acute Illness Ctr, Pittsburgh, PA 15261 USA. [Angus, Derek; Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15261 USA. [Newman, Anne B.] Univ Pittsburgh, Div Geriatr, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Lopez, Oscar] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA. [Kapur, Vishesh; Wilsdon, Anthony; Au, David; Fan, Vincent S.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Krishnan, Jerry A.] Univ Illinois, Sect Pulm Crit Care Sleep & Allergy, Chicago, IL USA. [Krishnan, Jerry A.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [Hansel, Nadia] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Au, David; Fan, Vincent S.] VA Puget Sound, HSR&D, Seattle, WA USA. [Avdalovic, Mark] Univ Calif Davis, Div Pulm & Crit Care Med, Davis, CA USA. [Barr, Graham] Columbia Univ, Dept Med, Med Ctr, New York, NY USA. [Barr, Graham] Columbia Univ, Dept Epidemiol, Med Ctr, New York, NY USA. RP Yende, S (reprint author), Univ Pittsburgh, 606D Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM yendes@upmc.edu RI Kapur, Vishesh/K-1054-2014; Tate, Judith/C-7447-2015; Newman, Anne/C-6408-2013; Angus, Derek/E-9671-2012 OI Kapur, Vishesh/0000-0002-5417-1097; Newman, Anne/0000-0002-0106-1150; FU NHLBI [HL080295]; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; Department of Veterans Affairs; [HHSN268201200036C]; [HHSN268200800007C]; [N01-HC-85079]; [N01-HC-85080]; [N01-HC-85081]; [N01-HC-85082]; [N01-HC-85083]; [N01-HC-85084]; [N01-HC-85085]; [N01-HC-85086]; [N01-HC-35129]; [N01-HC-15103]; [N01-HC-55222]; [N01-HC-75150]; [N01-HC-45133]; [K23 GM083215]; [R01GM097471] FX Supported by contracts HHSN268201200036C, HHSN268200800007C, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, and grant HL080295 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. Dr. Au is funded through the Department of Veterans Affairs. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. Dr. Yende is supported by K23 GM083215 and R01GM097471. NR 43 TC 39 Z9 39 U1 1 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2013 VL 188 IS 5 BP 586 EP 592 DI 10.1164/rccm.201212-2154OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 214BU UT WOS:000324106200014 PM 23848267 ER PT J AU Johannesmeyer, D Smith, V Cole, DJ Esnaola, NF Camp, ER AF Johannesmeyer, David Smith, Valerie Cole, David J. Esnaola, Nestor F. Camp, E. Ramsay TI The impact of lymph node disease in extremity soft-tissue sarcomas: a population-based analysis SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Lymph node; Sarcoma; Extremity; Prognosis ID METASTASIS; EPIDEMIOLOGY; SURVEILLANCE; SURVIVAL; DATABASE; REGISTRY; BIOPSY AB BACKGROUND: Because of the low incidence of regional lymph node metastasis, node-positive soft-tissue sarcoma patients remain poorly characterized. Our objective was to assess regional lymph node metastasis in extremity sarcoma patients using a large population database. METHODS: The Surveillance, Epidemiology, and End Results database was queried for extremity sarcoma patients. Clinicopathologic data and outcomes were examined to evaluate the significance of regional lymph node metastasis. RESULTS: Of 7,159 patients without distant metastasis, 64 patients had identified regional lymph node metastasis (.9%). Regional lymph node metastasis was associated with younger age, tumor grade, size, invasion, and tumor subtype. Excluding distant metastasis, lymph node status was the strongest prognostic factor (hazards ratio = 5.1, P < .001). CONCLUSIONS: Isolated regional lymph node metastasis is rare in extremity sarcoma patients. However, in the absence of distant metastasis, lymph node status is the most important prognostic factor. The management of positive lymph nodes remains uncertain although diagnosing lymph node metastasis may identify early biologically aggressive disease. Published by Elsevier Inc. C1 [Camp, E. Ramsay] Med Univ S Carolina, Dept Surg, Div Surg Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, Div Surg Oncol, 25 Courtenay Dr, Charleston, SC 29425 USA. EM campe@musc.edu NR 19 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2013 VL 206 IS 3 BP 289 EP 295 DI 10.1016/j.amjsurg.2012.10.043 PG 7 WC Surgery SC Surgery GA 213YK UT WOS:000324096400001 PM 23806824 ER PT J AU Patel, MS Ewing, T Kong, A Nguyen, D Lau, C Barrios, C Cinat, M Dolich, M Lekawa, M Malinoski, D AF Patel, Madhukar S. Ewing, Tyler Kong, Allen David Nguyen Lau, Cecilia Barrios, Cristobal Cinat, Marianne Dolich, Matthew Lekawa, Michael Malinoski, Darren TI Risk factors for venous thromboembolism in critically ill nontrauma surgical patients who cannot receive chemical prophylaxis SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the Southern-California-Chapter of the American-College-of-Surgeons CY JAN 22, 2011 CL Santa Barbara, CA SP Amer Coll Surg, So Calif Chapter DE Venous thromboembolism; Anticoagulation; Prophylaxis ID VENA-CAVA FILTERS; CHRONIC RENAL-DISEASE; DEEP-VEIN THROMBOSIS; INTENSIVE-CARE-UNIT; PULMONARY-EMBOLISM; TRAUMA PATIENTS; INFLAMMATION; PREVENTION; PLACEMENT; MORBIDITY AB BACKGROUND: We sought to identify independent predictors of venous thromboembolism in critically ill general surgery patients who cannot receive chemical prophylaxis in order to identify those who may benefit from aggressive screening and/or prophylactic inferior vena cava filter placement. METHODS: Nontrauma patients in the surgical intensive care unit were prospectively followed for 2 years. Patients who had contraindications to prophylactic anticoagulation and received routine screening duplex examinations were included. Data regarding lower-extremity deep venous thrombosis or pulmonary embolism (PE) rates, past medical history (PMH), surgeries, and transfusions were collected. Logistic regression was used to identify independent predictors of lower-extremity deep venous thrombosis or PE (venous thromboembolism) with a P < .05. RESULTS: Data were complete for 204 patients. Twenty (9.8%) patients developed venous thromboembolism. Independent predictors of venous thromboembolism included postoperative blood product requirements (odds ratio 5 1.04 per unit), a PMH of PE (OR = 10.1), and a PMH of renal insufficiency (odds ratio = 5.1). CONCLUSIONS: Aggressive screening and/or prophylactic inferior vena cava filter may be considered when prophylactic anticoagulation is prohibited in patients with increased postoperative transfusion requirements or a PMH of either PE or renal insufficiency. (C) 2013 Elsevier Inc. All rights reserved. C1 [Patel, Madhukar S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ewing, Tyler; Kong, Allen; David Nguyen; Lau, Cecilia; Barrios, Cristobal; Cinat, Marianne; Dolich, Matthew; Lekawa, Michael] Univ Calif Irvine, Div Trauma & Crit Care, Irvine, CA USA. [Malinoski, Darren] Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR USA. RP Malinoski, D (reprint author), Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR USA. EM malinosk@ohsu.edu NR 28 TC 0 Z9 0 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2013 VL 206 IS 3 BP 300 EP 306 DI 10.1016/j.amjsurg.2012.10.040 PG 7 WC Surgery SC Surgery GA 213YK UT WOS:000324096400003 PM 23759695 ER PT J AU Han, G Ren, JN Liu, S Gu, GS Ren, HJ Yan, DS Chen, J Wang, GF Zhou, B Wu, XW Yuan, YJ Li, JS AF Han, Gang Ren, Jianan Liu, Song Gu, Guosheng Ren, Huajian Yan, Dongsheng Chen, Jun Wang, Gefei Zhou, Bo Wu, Xiuwen Yuan, Yujie Li, Jieshou TI Nonthyroidal illness syndrome in enterocutaneous fistulas SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Enterocutaneous fistula; Nonthyroidal illness syndrome; Outcomes; Prognosis; Etiology ID INTENSIVE-CARE-UNIT; EUTHYROID SICK SYNDROME; THYROID-HORMONE LEVELS; CRITICALLY-ILL PATIENTS; DANGEROUS DOGMAS; FUNCTION TESTS; PREDICTION; MORTALITY; FAILURE; HYPOTHYROIDISM AB BACKGROUND: The aim of this study was to investigate the incidence, etiology, clinical outcomes, and prognosis of nonthyroidal illness syndrome (NTIS) in patients with enterocutaneous fistulas. METHODS: We prospectively collected 226 patients with enterocutaneous fistulas. Demographics, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment scores, C-reactive protein, body mass index, albumin, and thyroidal hormones were evaluated for each patient. RESULTS: The incidence of NTIS was 57.5% in patients with enterocutaneous fistulas. Age and the APACHE II and Sequential Organ Failure Assessment scores were significantly higher, whereas albumin was lower in the NTIS group compared with those in the euthyroid group. A decreased sum activity of deiodinases and a reduced ratio of total thyroxin/free thyroxin and total triiodothyronine/free triiodothyronine were observed in the NTIS group. Patients with NTIS suffered longer durations in the intensive care unit and higher possibilities of mechanical ventilation. The cumulative survival rate was significantly lower in the NTIS group. CONCLUSIONS: NTIS was common, and patients with NTIS displayed worse clinical outcome and prognosis. A hypodeiodination condition and a potential thyroid hormone-binding dysfunction may play a role in the etiology of NTIS. A low serum albumin concentration and a high APACHE II score were risk factors of NTIS in enterocutaneous fistulas. (C) 2013 Elsevier Inc. All rights reserved. C1 [Han, Gang; Ren, Jianan; Liu, Song; Gu, Guosheng; Ren, Huajian; Yan, Dongsheng; Chen, Jun; Wang, Gefei; Zhou, Bo; Wu, Xiuwen; Yuan, Yujie; Li, Jieshou] Nanjing Univ, Sch Med, Jinling Hosp, Dept Surg, Nanjing 210008, Jiangsu, Peoples R China. [Han, Gang] Jilin Univ, Gen Surg Ctr, Hosp 2, Dept Gen Surg, Changchun 130023, Peoples R China. [Liu, Song] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Liu, Song] Harvard Univ, Sch Med, Boston, MA USA. RP Ren, JN (reprint author), Nanjing Univ, Sch Med, Jinling Hosp, Dept Surg, 305 East Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. EM jiananr@gmail.com OI LIU, SONG/0000-0002-4780-9697; Ren, Jianan/0000-0002-7978-8093 FU Climb Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars [BK2010017] FX Supported by grants from Climb Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars (no. BK2010017). NR 34 TC 5 Z9 6 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2013 VL 206 IS 3 BP 386 EP 392 DI 10.1016/j.amjsurg.2012.12.011 PG 7 WC Surgery SC Surgery GA 213YK UT WOS:000324096400016 PM 23809674 ER PT J AU Baker, RR AF Baker, Rodney R. TI Robert Spurlin Waldrop (1912-2012) OBITUARY SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 [Baker, Rodney R.] Dept Vet Affairs, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD SEP PY 2013 VL 68 IS 6 BP 473 EP 473 DI 10.1037/a0033585 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 217FP UT WOS:000324342800010 PM 24016122 ER PT J AU Carlozzi, NE Fyffe, D Morin, KG Byrne, R Tulsky, DS Victorson, D Lai, JS Wecht, JM AF Carlozzi, Noelle E. Fyffe, Denise Morin, Kel G. Byrne, Rachel Tulsky, David S. Victorson, David Lai, Jin-Shei Wecht, Jill M. TI Impact of Blood Pressure Dysregulation on Health-Related Quality of Life in Persons With Spinal Cord Injury: Development of a Conceptual Model SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Meeting of the Academy-of-Spinal-Cord-Injury-Professionals CY SEP 03-05, 2012 CL Las Vegas, NV SP Acad Spinal Cord Injury Profess DE Blood pressure; Outcome assessment (health care); Quality of life; Rehabilitation; Spinal cord injuries ID PATIENT-REPORTED OUTCOMES; CARDIOVASCULAR-DISEASE RISK; ORTHOSTATIC HYPOTENSION; AUTONOMIC DYSREFLEXIA; COGNITIVE PERFORMANCE; NEUROLOGICAL LEVEL; FUNCTIONAL INDEX; TETRAPLEGIA; PARAPLEGIA; ASSOCIATION AB Objectives: To identify medically relevant aspects of blood pressure dysregulation (BPD) related to quality of life in individuals with spinal cord injury (SCI), and to propose an integrated conceptual framework based on input from both individuals with SCI and their clinical providers. This framework will serve as a guide for the development of a patient-reported outcome (PRO) measure specifically related to BPD. Design: Three focus groups with individuals with SCI and 3 groups with SCI providers were analyzed using grounded-theory based qualitative analysis to ascertain how blood pressure impacts health-related quality of life (HRQOL) in individuals with SCI. Setting: Focus groups were conducted at 2 Veterans Affairs medical centers and a research center. Participants: Individuals with SCI (n=27) in 3 focus groups and clinical providers (n=25) in 3 focus groups. Interventions: Not applicable. Main Outcome Measures: Not applicable. Results: Qualitative analysis indicated that all focus groups spent the highest percentage of time discussing symptoms of BPD (39%), followed by precipitators/causes of BPD (16%), preventative actions (15%), corrective actions (12%), and the impact that BPD has on social or emotional functioning (8%). While patient/consumer focus groups and provider focus groups raised similar issues, providers spent more time discussing precipitators/causes of BPD and preventative actions (38%) than patient/consumer groups (24%). Conclusions: These results suggest that BPD uniquely and adversely impacts HRQOL in persons with SCI. While both individuals with SCI and their providers highlighted the relevant symptoms of BPD, the SCI providers offered additional detailed information regarding the precipitators/causes and what can be done to prevent/treat BPD. Further, the results suggest that persons with SCI are aware of how BPD impacts their HRQOL and are able to distinguish between subtle signs and symptoms. These findings exemplify the need for a validated and sensitive clinical measurement tool that can assess the extent to which BPD impacts HRQOL in patients with SCI. (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Carlozzi, Noelle E.; Tulsky, David S.] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. [Fyffe, Denise; Byrne, Rachel] Kessler Fdn Res Ctr, Spinal Cord Injury Outcomes & Assessment Lab, W Orange, NJ USA. [Fyffe, Denise] Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. [Morin, Kel G.; Wecht, Jill M.] James J Peters Vet Affairs Med Ctr, Rehabil Res & Dev Serv, Bronx, NY USA. [Victorson, David; Lai, Jin-Shei] Northwestern Univ, Dept Med & Social Sci, Chicago, IL 60611 USA. [Wecht, Jill M.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Wecht, Jill M.] Mt Sinai Sch Med, New York, NY USA. RP Carlozzi, NE (reprint author), Univ Michigan, Ctr Rehabil Outcomes & Assessment Res, Dept Phys Med & Rehabil, North Campus Res Complex,2800 Plymouth Rd,Bldg NC, Ann Arbor, MI 48109 USA. EM carlozzi@med.umich.edu FU RRD VA [I01 RX000405] NR 58 TC 7 Z9 7 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2013 VL 94 IS 9 BP 1721 EP 1730 DI 10.1016/j.apmr.2013.02.024 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 214QZ UT WOS:000324151900011 PM 23499779 ER PT J AU Parnes, N DeFranco, M Wells, JH Higgins, LD Warner, JJP AF Parnes, Nata DeFranco, Michael Wells, Jessica H. Higgins, Laurence D. Warner, Jon J. P. TI Complications After Arthroscopic Revision Rotator Cuff Repair SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID SINGLE-ROW; INTEGRITY; OUTCOMES; SURGERY AB Purpose: The purpose of this study was to determine the complication rate of arthroscopic revision rotator cuff repair (ARRCR). Methods: The retrospective review included 94 patients who underwent ARRCR performed by the 2 senior authors between January 2000 and June 2009 (mean age, 52 years; age range, 44 to 72 years). Sixty-four patients underwent 1 revision rotator cuff repair, 23 patients underwent 2 revisions, and 7 patients underwent 3 or more revisions. The rotator cuff tear at the time of the revision was characterized as massive (>5 cm) in 51 patients (54%), large (>3 to 5 cm) in 14 patients (15%), medium (1 to 3 cm) in 17 patients (18%), and small (<1 cm) in 12 patients (13%). There was a single-tendon tear in 12 patients (13%), 2 tears in 31 patients (33%), and 3 or 4 tears in 51 patients (54%). Additional procedures included revision acromioplasty (n = 66), distal clavicular excision (n = 19), biceps tenodesis (n = 52), suprascapular nerve release (n = 14), and loose anchor removal (n = 6). Results: Complications developed in 19 patients (20.2%) within 1 year of undergoing ARRCR. The complications included failure to heal (10.6%, n = 10), stiffness (7.4%, n = 7), infection (2.1%, n = 2), and nerve injury (1.1%, n = 1). A direct correlation was found between the complication rate and the number of revision surgeries: 14% after 1 revision, 17.4% after 2 revisions, 33% after 3 revisions, and 50% after 4 or more revisions. The minimum follow-up of all the patients in this study was 1 year. We continued to follow up every patient who was diagnosed with complications during this year until resolution of the complication, or we are still continuing to perform follow-up of these patients. Conclusions: The complication rate after ARRCR is about twice the published rate for primary rotator cuff repair. There is a direct correlation between the complication rate and the number of revision surgeries. The most common complication recognized was failure to heal because of poor tissue quality. Level of Evidence: Level IV, therapeutic case series. C1 [Parnes, Nata; DeFranco, Michael; Wells, Jessica H.; Higgins, Laurence D.] Brigham & Womens Hosp, Harvard Shoulder Serv, Boston, MA 02115 USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Higgins, LD (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, Shoulder & Sports Med Serv, 75 Francis St, Boston, MA 02115 USA. EM LDHiggins@partners.org FU San Diego Shoulder Institute FX The authors report the following potential conflict of interest or source of funding: J.J.P.W. receives support from San Diego Shoulder Institute. NR 23 TC 11 Z9 11 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD SEP PY 2013 VL 29 IS 9 BP 1479 EP 1486 DI 10.1016/j.arthro.2013.06.015 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 213BX UT WOS:000324029500008 PM 23992986 ER PT J AU Guan, J Mishra, S Shi, JR Plovie, E Qiu, YL Cao, X Gianni, D Jiang, BB del Monte, F Connors, LH Seldin, DC Lavatelli, F Rognoni, P Palladini, G Merlini, G Falk, RH Semigran, MJ Dec, GW MacRae, CA Liao, RL AF Guan, Jian Mishra, Shikha Shi, Jianru Plovie, Eva Qiu, Yiling Cao, Xin Gianni, Davide Jiang, Bingbing del Monte, Federica Connors, Lawreen H. Seldin, David C. Lavatelli, Francesca Rognoni, Paola Palladini, Giovanni Merlini, Giampaolo Falk, Rodney H. Semigran, Marc J. Dec, G. William, Jr. MacRae, Calum A. Liao, Ronglih TI Stanniocalcin1 is a key mediator of amyloidogenic light chain induced cardiotoxicity SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE Amyloidosis; Cardiomyopathy; Cardiac toxicity ID CARDIAC AMYLOIDOSIS; OXIDATIVE STRESS; TRANSGENIC MICE; AL AMYLOIDOSIS; CANCER-CELLS; DYSFUNCTION; CARDIOMYOCYTES; INHIBITOR; APOPTOSIS; PROTEINS AB Immunoglobulin light chain (LC) amyloidosis (AL) results from overproduction of circulating amyloidogenic LC proteins and subsequent amyloid fibril deposition in organs. Mortality in AL amyloidosis patients is highly associated with a rapidly progressive AL cardiomyopathy, marked by profound impairment of diastolic and systolic cardiac function and significant early mortality. While myocardial fibril deposition contributes to the severe diastolic dysfunction seen in AL cardiomyopathy patients, the degree of fibril deposition has not been found to correlate with prognosis. Previously, we and others showed a direct cardiotoxic effect of amyloidogenic LC proteins (AL-LC), which may contribute to the pathophysiology and mortality observed in AL cardiomyopathy patients. However, the mechanisms underlying AL-LC related cardiotoxicity remain unknown. Mammalian stanniocalcin1 (STC1) is associated with a number of cellular processes including oxidative stress and cell death. Herein, we find that STC1 expression is elevated in cardiac tissue from AL cardiomyopathy patients, and is induced in isolated cardiomyocytes in response to AL-LC, but not non-amyloidogenic LC. STC1 overexpression in vitro recapitulates the pathophysiology of AL-LC mediated cardiotoxicity, with increased ROS production, contractile dysfunction and cell death. Overexpression of STC1 in vivo results in significant cardiac dysfunction and cell death. Genetic silencing of STC1 prevents AL-LC induced cardiotoxicity in cardiomyocytes and protects against AL-LC induced cell death and early mortality in zebrafish. The cardiotoxic effects of STC1 appears to be mediated via mitochondrial dysfunction as indicated by loss of mitochondrial membrane potential, ROS production and increased mitochondrial calcium levels. Collectively, this work identifies STC1 as a critical determinant of AL-LC cardiotoxicity. C1 [Guan, Jian; Mishra, Shikha; Shi, Jianru; Plovie, Eva; Qiu, Yiling; Cao, Xin; Jiang, Bingbing; MacRae, Calum A.; Liao, Ronglih] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 02115 USA. [Guan, Jian; Mishra, Shikha; Shi, Jianru; Qiu, Yiling; Cao, Xin; Jiang, Bingbing; Liao, Ronglih] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. [Guan, Jian; Mishra, Shikha; Shi, Jianru; Plovie, Eva; Qiu, Yiling; Cao, Xin; Jiang, Bingbing; del Monte, Federica; Semigran, Marc J.; Dec, G. William, Jr.; MacRae, Calum A.; Liao, Ronglih] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Guan, Jian] Boston Univ, Sch Med, Mol Med Grad Program, Boston, MA 02115 USA. [Gianni, Davide] Univ Massachusetts, Sch Med, Worcester, MA USA. [del Monte, Federica] Beth Israel Deaconess Med Ctr, Dept Med, Cardiovasc Inst, Boston, MA 02215 USA. [Connors, Lawreen H.; Seldin, David C.] Boston Univ, Sch Med, Amyloid Res & Treatment Program, Boston, MA 02115 USA. [Lavatelli, Francesca; Rognoni, Paola; Palladini, Giovanni; Merlini, Giampaolo] Univ Pavia, Amyloid Res & Treatment Ctr, I-27100 Pavia, Italy. [Falk, Rodney H.; Liao, Ronglih] Brigham & Womens Hosp, Cardiac Amyloidosis Program, Boston, MA 02115 USA. [Semigran, Marc J.; Dec, G. William, Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Liao, RL (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, 77 Ave Louis Pasteur,NRB 431, Boston, MA 02115 USA. EM rliao@rics.bwh.harvard.edu RI Palladini, Giovanni/G-1763-2010; OI Palladini, Giovanni/0000-0001-5994-5138; Merlini, Giampaolo/0000-0001-7680-3254; Connors, Lawreen/0000-0002-4672-4296 FU National Institutes of Health (NIH) [HL088533, HL086967, HL093148, HL099073, DK90696, AG031804]; American Heart Association; Cardiac Amyloidosis Program, BWH; Gruss and Wildflower Foundations; Amyloid Research Fund at BU; Associazione Italiana per la Ricercasul Cancro Special Program 5x mille, Molecular Clinical Oncology; NIH T32 [T32HL007604] FX The authors thank Ms. Wendy Du at Carnegie Mellon University, Mr. Soeun Ngoy at the Brigham and Women's Hospital (BWH) Cardiovascular Physiology Core, Ms. Gloria Chan at Boston University (BU) Amyloidosis Center for excellent technical assistances and Drs. Yingyi Zhang, Judith Gwathmey and Thomas E. Macgillivray for providing critical reagents. This work was supported, in part, by the National Institutes of Health (NIH), HL088533, HL086967, HL093148, HL099073 (R. L.), DK90696 (D. C. S.), AG031804 (L. H. C.), American Heart Association (C. A. M.), and the Cardiac Amyloidosis Program, BWH (R. H. F., R. L.) and the Gruss and Wildflower Foundations and the Amyloid Research Fund at BU (L. H. C., D. C. S.). G. M. is supported by Associazione Italiana per la Ricercasul Cancro Special Program 5x mille, Molecular Clinical Oncology. S. M. is supported by NIH T32 (T32HL007604). NR 45 TC 16 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 PY 2013 VL 108 IS 5 AR 378 DI 10.1007/s00395-013-0378-5 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 215LU UT WOS:000324212500010 PM 23982491 ER PT J AU Fairholme, CP Nosen, EL Nillni, YI Schumacher, JA Tull, MT Coffey, SF AF Fairholme, Christopher P. Nosen, Elizabeth L. Nillni, Yael I. Schumacher, Julie A. Tull, Matthew T. Coffey, Scott F. TI Sleep disturbance and emotion dysregulation as transdiagnostic processes in a comorbid sample SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Insomnia; Emotion regulation; Transdiagnostic; PTSD; Alcohol dependence; Difficulties in Emotion Regulation Scale ID COGNITIVE-BEHAVIORAL THERAPY; POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; PSYCHIATRIC-DISORDERS; REGULATION SCALE; SOCIAL ANXIETY; ALCOHOL-USE; INSOMNIA; DEPRESSION; DIFFICULTIES AB Sleep disturbance and emotion dysregulation have been identified as etiologic and maintaining factors for a range of psychopathology and separate literatures support their relationships to anxiety, depression, PTSD, and alcohol dependence (AD) symptom severity. Previous studies have examined these relationships in isolation, failing to account for the high rates of comorbidity among disorders. It is not yet known whether these processes uniquely predict symptom severity in each of these domains. Participants were 220 patients in residential substance abuse treatment, who had experienced a potentially traumatic event and exceeded screening cutoffs for probable PTSD and problematic alcohol use. Controlling for emotion dysregulation and the interrelationships among the outcome variables, insomnia was uniquely associated with anxiety (B = .27, p < .001), depression (B = .25, p < .001), PTSD (B = .22, p < .001), and AD (B = .17, p = .01) symptom severity. Similarly, controlling for insomnia, emotion dysregulation was uniquely associated with anxiety (B = .40, p < .001), depression (B = .47, p < .001), PTSD (B = .38, p < .001), and AD (B = .26, p < .001) symptom severity. Insomnia and emotion dysregulation appear to be transdiagnostic processes uniquely associated with symptom severity across a number of different domains and might be important treatment targets for individuals with PTSD and AD. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Fairholme, Christopher P.; Nosen, Elizabeth L.; Nillni, Yael I.; Schumacher, Julie A.; Tull, Matthew T.; Coffey, Scott F.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Fairholme, Christopher P.] Stanford Univ, Stanford, CA 94305 USA. [Nillni, Yael I.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. RP Coffey, SF (reprint author), Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, 2500 North State St, Jackson, MS 39216 USA. EM cfairholme@stanford.edu; scoffey@umc.edu FU NIAAA NIH HHS [R01 AA016816, R01AA016816] NR 61 TC 20 Z9 20 U1 7 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD SEP PY 2013 VL 51 IS 9 BP 540 EP 546 DI 10.1016/j.brat.2013.05.014 PG 7 WC Psychology, Clinical SC Psychology GA 212UC UT WOS:000324007300004 PM 23831496 ER PT J AU Greer, JA Jackson, VA Meier, DE Temel, JS AF Greer, Joseph A. Jackson, Vicki A. Meier, Diane E. Temel, Jennifer S. TI Early integration of palliative care services with standard oncology care for patients with advanced cancer SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review DE palliative care; metastatic cancer; quality of life; end of life ID END-OF-LIFE; CELL LUNG-CANCER; HEALTH-CARE; TREATMENT PREFERENCES; NEAR-DEATH; RECEIVING CHEMOTHERAPY; DISCUSSING PROGNOSIS; PROSPECTIVE COHORT; REFERRAL PRACTICES; METASTATIC CANCER AB Answer questions and earn CME/CNE Scientific advances in novel cancer therapeutics have led to remarkable changes in oncology practice and longer lives for patients diagnosed with incurable malignancies. However, the myriad options for treatment have established a culture of cancer care that has not been matched with a similar availability of efficacious supportive care interventions aimed at relieving debilitating symptoms due to progressive disease and treatment side effects. Accumulating data show that the introduction of palliative care services at the time of diagnosis of advanced cancer leads to meaningful improvement in the experiences of patients and family caregivers by emphasizing symptom management, quality of life, and treatment planning. In this review article, the rationale and evidence base for this model of early palliative care services integrated into standard oncology care are presented. In addition, the implications and limitations of the existing data to 1) elucidate the mechanisms by which early palliative care benefits patients and families; 2) guide the dissemination and application of this model in outpatient settings; and 3) inform health care policy regarding the delivery of high-quality, cost-effective, and comprehensive cancer care are discussed. CA Cancer J Clin 2013;63:349-363. ((c)) 2013 American Cancer Society, Inc. C1 [Greer, Joseph A.; Jackson, Vicki A.; Temel, Jennifer S.] Harvard Univ, Sch Med, Boston, MA USA. [Greer, Joseph A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Jackson, Vicki A.] Massachusetts Gen Hosp, Dept Med, Palliat Care Unit, Boston, MA 02114 USA. [Meier, Diane E.] Mt Sinai Med Ctr, Ctr Adv Palliat Care, New York, NY 10029 USA. [Meier, Diane E.] Mt Sinai Med Ctr, Hertzberg Palliat Care Inst, New York, NY 10029 USA. [Meier, Diane E.] Mt Sinai Med Ctr, Mt Sinai Sch Med, New York, NY 10029 USA. [Temel, Jennifer S.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Greer, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM jgreer2@partners.org FU American Society of Clinical Oncology Career Development Award FX Supported in part by an American Society of Clinical Oncology Career Development Award to Dr. Temel and gifts from the Joanne Hill Monahan Cancer Fund and Golf Fights Cancer. NR 122 TC 51 Z9 53 U1 5 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD SEP PY 2013 VL 63 IS 5 BP 349 EP 363 DI 10.3322/caac.21192 PG 15 WC Oncology SC Oncology GA 213BT UT WOS:000324029100005 PM 23856954 ER PT J AU Kim, MB Chen, MH de Castro, M Loffredo, M Kantoff, PW D'Amico, AV AF Kim, Miranda B. Chen, Ming-Hui de Castro, Mario Loffredo, Marian Kantoff, Philip W. D'Amico, Anthony V. TI Defining the optimal approach to the patient with postradiation prostate-specific antigen recurrence using outcome data from a prospective randomized trial SO CANCER LA English DT Article DE prostate cancer; radiation therapy; androgen suppression therapy; comorbidity; prostate-specific antigen ID ANDROGEN-DEPRIVATION THERAPY; CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; INCREASED SURVIVAL; SCREENING TRIAL; FOLLOW-UP; SUPPRESSION; COMORBIDITY; RISK AB BACKGROUND Optimal management remains unknown following prostate-specific antigen (PSA) failure when considering comorbidity and PSA kinetics at recurrence. In order to define randomized controlled trials (RCTs) that can address this issue, this study examined factors associated with the risk of death following PSA failure. METHODS Of 206 men randomized to RT with or without 6 months of androgen suppression therapy (AST), 108 sustained PSA failure and began AST when PSA approached 10 ng/mL and formed the study cohort. Cox regression multivariable analysis was used to determine factors associated with death following PSA failure. RESULTS After a median follow-up of 10.3 years of 108 men with PSA failure, 64 (59%) died, with 22 (34%) dying of prostate cancer (PC). Increasing PSA velocity at recurrence was associated with a significant increase in the risk of death (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.45; P=.03). Among men with no/minimal versus moderate/severe comorbidity, PC comprised 42% (20 of 48) versus 12.5% (2 of 16) of all deaths, respectively. Estimates of PC-specific and all-cause death were significantly higher when PSA velocity was greater than as compared with the median or less in men with no/minimal (P<.008) but not moderate/severe comorbidity (P>.15). CONCLUSIONS Despite unfavorable PSA kinetics at recurrence, unhealthy men may not benefit from AST; RCTs examining intermittent AST versus surveillance are needed. For healthy men with unfavorable PSA kinetics at recurrence, PC death rates are high despite AST, which warrants RCTs to evaluate the impact on death when adding agents that prolong survival in men with metastatic castration-resistant PC to AST. Cancer 2013;119:3280-6. (c) 2013 American Cancer Society. C1 [Kim, Miranda B.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [de Castro, Mario] Univ Sao Paulo, Dept Appl Math & Stat, Sao Paulo, Brazil. [Loffredo, Marian; Kantoff, Philip W.; D'Amico, Anthony V.] Dana Farber Canc Inst, Dept Med Oncol & Radiat Oncol, Boston, MA 02115 USA. [Kim, Miranda B.; Loffredo, Marian; Kantoff, Philip W.; D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kim, MB (reprint author), Brigham & Womens Hosp, ASB1 L2,75 Francis St, Boston, MA 02115 USA. EM mbkim@partners.org NR 30 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP PY 2013 VL 119 IS 18 BP 3280 EP 3286 DI 10.1002/cncr.28202 PG 7 WC Oncology SC Oncology GA 211EN UT WOS:000323887900007 PM 23798006 ER PT J AU Dowling, EC Chawla, N Forsythe, LP de Moor, J McNeel, T Rozjabek, HM Ekwueme, DU Yabroff, KR AF Dowling, Emily C. Chawla, Neetu Forsythe, Laura P. de Moor, Janet McNeel, Timothy Rozjabek, Heather M. Ekwueme, Donatus U. Yabroff, K. Robin TI Lost productivity and burden of illness in cancer survivors with and without other chronic conditions SO CANCER LA English DT Article DE MEPS; quality of life; cancer survivors; chronic conditions; comorbidities ID MENTAL-HEALTH STATUS; QUALITY-OF-LIFE; CARE; LIMITATIONS; RECORDS; AGE AB BACKGROUND Cancer survivors may experience long-term and late effects from treatment that adversely affect health and limit functioning. Few studies examine lost productivity and disease burden in cancer survivors compared with individuals who have other chronic conditions or by cancer type. METHODS We identified 4960 cancer survivors and 64,431 other individuals from the 2008-2010 Medical Expenditure Panel Survey and compared multiple measures of disease burden, including health status and lost productivity, between conditions and by cancer site for cancer survivors. All analyses controlled for the effects of age, sex, race/ethnicity, and number of comorbid conditions. RESULTS Overall, in adjusted analyses in multiple models, cancer survivors with another chronic disease (heart disease or diabetes) experienced higher levels of burden compared with individuals with a history of cancer only, chronic disease only, and neither cancer, heart disease, nor diabetes across multiple measures (P<.05). Among cancer survivors, individuals with short survival cancers and multiple cancers consistently had the highest levels of burden across multiple measures (P<.0001). CONCLUSIONS Cancer survivors who have another chronic disease experience more limitations and higher levels of burden across multiple measures. Limitations are particularly severe in cancer survivors with short survival cancer and multiple cancers. Cancer 2013;119:3393-401. (c) 2013 American Cancer Society. C1 [Dowling, Emily C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Chawla, Neetu; Forsythe, Laura P.; de Moor, Janet; Rozjabek, Heather M.; Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [McNeel, Timothy] Informat Management Serv Inc, Rockville, MD USA. [Ekwueme, Donatus U.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Dowling, EC (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM edowling@mgh-ita.org OI Yabroff, K. Robin/0000-0003-0644-5572 NR 27 TC 14 Z9 14 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP PY 2013 VL 119 IS 18 BP 3393 EP 3401 DI 10.1002/cncr.28214 PG 9 WC Oncology SC Oncology GA 211EN UT WOS:000323887900021 PM 23794146 ER PT J AU Xu, J Haigis, KM Firestone, AJ McNerney, ME Li, Q Davis, E Chen, SC Nakitandwe, J Downing, J Jacks, T Le Beau, MM Shannon, K AF Xu, Jin Haigis, Kevin M. Firestone, Ari J. McNerney, Megan E. Li, Qing Davis, Elizabeth Chen, Shann-Ching Nakitandwe, Joy Downing, James Jacks, Tyler Le Beau, Michelle M. Shannon, Kevin TI Dominant Role of Oncogene Dosage and Absence of Tumor Suppressor Activity in Nras-Driven Hematopoietic Transformation SO CANCER DISCOVERY LA English DT Article ID MYELOMONOCYTIC LEUKEMIA; DEVELOPMENTAL DEFECTS; MUTATIONS; RAS; MALIGNANCIES; PROGRESSION; NUMBER; CANCER; PROLIFERATION; CHROMOSOME-7 AB Biochemical properties of Ras oncoproteins and their transforming ability strongly support a dominant mechanism of action in tumorigenesis. However, genetic studies unexpectedly suggested that wild-type (WT) Ras exerts tumor suppressor activity. Expressing oncogenic Nras(G12D) in the hematopoietic compartment of mice induces an aggressive myeloproliferative neoplasm that is exacerbated in homozygous mutant animals. Here, we show that increased Nras(G12D) gene dosage, but not inactivation of WT Nras, underlies the aggressive in vivo behavior of Nras(G12D/G12D) hematopoietic cells. Modulating Nras(G12D) dosage had discrete effects on myeloid progenitor growth, signal transduction, and sensitivity to MAP-ERK kinase (MEK) inhibition. Furthermore, enforced WT N-Ras expression neither suppressed the growth of Nras-mutant cells nor inhibited myeloid transformation by exogenous Nras(G12D). Importantly, NRAS expression increased in human cancer cell lines with NRAS mutations. These data have therapeutic implications and support reconsidering the proposed tumor suppressor activity of WT Ras in other cancers. SIGNIFICANCE: Understanding the mechanisms of Ras-induced transformation and adaptive cellular responses is fundamental. The observation that oncogenic Nras lacks tumor suppressor activity, whereas increased dosage strongly modulates cell growth and alters sensitivity to MEK inhibition, suggests new therapeutic opportunities in cancer. (C) 2013 AACR. C1 [Xu, Jin; Firestone, Ari J.; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Shannon, Kevin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Jacks, Tyler] MIT, Dept Biol, David H Koch Inst Integrat Canc Res, Cambridge, MA USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA USA. [McNerney, Megan E.] Univ Chicago, Dept Pathol, Inst Genom & Syst Biol, Chicago, IL 60637 USA. [Davis, Elizabeth] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Le Beau, Michelle M.] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA. [Le Beau, Michelle M.] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA. [Li, Qing] Univ Michigan, Dept Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Chen, Shann-Ching; Nakitandwe, Joy; Downing, James] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. RP Shannon, K (reprint author), 1450 3rd St,Room HD 240, San Francisco, CA 94158 USA. EM shannonk@peds.ucsf.edu OI Firestone, Ari/0000-0001-9902-443X FU NIH [R37CA72614, P01CA40046, K08CA134649]; Specialized Center of Research award from the Leukemia and Lymphoma Society [LLS 7019-04]; American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital; American Cancer Society; Damon Runyon Cancer Research Foundation [DRG-2149-13] FX This work was supported by NIH grants R37CA72614, P01CA40046, and K08CA134649, a Specialized Center of Research award from the Leukemia and Lymphoma Society (LLS 7019-04), the American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital, an American Cancer Society Fellowship (to J. Xu), and a Damon Runyon Cancer Research Foundation Fellowship (DRG-2149-13; to A.J. Firestone). NR 26 TC 22 Z9 23 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD SEP PY 2013 VL 3 IS 9 BP 993 EP 1001 DI 10.1158/2159-8290.CD-13-0096 PG 9 WC Oncology SC Oncology GA 215YH UT WOS:000324246600021 PM 23733505 ER PT J AU Korpal, M Korn, JM Gao, XL Rakiec, DP Ruddy, DA Doshi, S Yuan, J Kovats, SG Kim, S Cooke, VG Monahan, JE Stegmeier, F Roberts, TM Sellers, WR Zhou, WL Zhu, P AF Korpal, Manav Korn, Joshua M. Gao, Xueliang Rakiec, Daniel P. Ruddy, David A. Doshi, Shivang Yuan, Jing Kovats, Steve G. Kim, Sunkyu Cooke, Vesselina G. Monahan, John E. Stegmeier, Frank Roberts, Thomas M. Sellers, William R. Zhou, Wenlai Zhu, Ping TI An F876L Mutation in Androgen Receptor Confers Genetic and Phenotypic Resistance to MDV3100 (Enzalutamide) SO CANCER DISCOVERY LA English DT Article ID ANTIANDROGEN WITHDRAWAL SYNDROME; ADVANCED PROSTATE-CANCER; DIRECTED THERAPIES; ANTIGEN DECLINE; LNCAP CELLS; STATISTICS; DOMAIN AB Castration-resistant prostate cancer (CRPC) is the most aggressive, incurable form of prostate cancer. MDV3100 (enzalutamide), an antagonist of the androgen receptor (AR), was approved for clinical use in men with metastatic CRPC. Although this compound showed clinical efficacy, many initial responders later developed resistance. To uncover relevant resistant mechanisms, we developed a model of spontaneous resistance to MDV3100 in LNCaP prostate cancer cells. Detailed characterization revealed that emergence of an F876L mutation in AR correlated with blunted AR response to MDV3100 and sustained proliferation during treatment. Functional studies confirmed that AR F876L confers an antagonist-to-agonist switch that drives phenotypic resistance. Finally, treatment with distinct antiandrogens or cyclin-dependent kinase (CDK) 4/6 inhibitors effectively antagonized AR F876L function. Together, these findings suggest that emergence of F876L may (i) serve as a novel biomarker for prediction of drug sensitivity, (ii) predict a "withdrawal" response to MDV3100, and (iii) be suitably targeted with other antiandrogens or CDK4/6 inhibitors. SIGNIFICANCE: We uncovered an F876L agonist-switch mutation in AR that confers genetic and phenotypic resistance to the antiandrogen drug MDV3100. On the basis of this finding, we propose new therapeutic strategies to treat patients with prostate cancer presenting with this AR mutation. (C) 2013 AACR. C1 [Korpal, Manav; Korn, Joshua M.; Doshi, Shivang; Yuan, Jing; Kovats, Steve G.; Kim, Sunkyu; Cooke, Vesselina G.; Stegmeier, Frank; Sellers, William R.; Zhou, Wenlai; Zhu, Ping] Novartis Inst BioMed Res, Oncol Dis Area, Cambridge, MA 02139 USA. [Rakiec, Daniel P.; Ruddy, David A.; Monahan, John E.] Novartis Inst BioMed Res, Dept Oncol Translat Med, Cambridge, MA 02139 USA. [Gao, Xueliang; Roberts, Thomas M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Korpal, M (reprint author), Novartis Inst BioMed Res, Oncol Dis Area, 250 Massachusetts Ave, Cambridge, MA 02139 USA. EM manav.korpal@outlook.com; William.Sellers@novartis.com OI Monahan, John/0000-0002-3125-8704 FU Novartis Institutes for BioMedical Research FX All studies were funded by Novartis Institutes for BioMedical Research. M. Korpal is a recipient of the presidential postdoctoral fellowship from Novartis Institutes for BioMedical Research. NR 30 TC 166 Z9 169 U1 1 U2 22 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD SEP PY 2013 VL 3 IS 9 BP 1030 EP 1043 DI 10.1158/2159-8290.CD-13-0142 PG 14 WC Oncology SC Oncology GA 215YH UT WOS:000324246600023 PM 23842682 ER PT J AU Hagerstrand, D Tong, A Schumacher, SE Ilic, N Shen, RR Cheung, HW Vazquez, F Shrestha, Y Kim, SY Giacomelli, AO Rosenbluh, J Schinzel, AC Spardy, NA Barbie, DA Mermel, CH Weir, BA Garraway, LA Tamayo, P Mesirov, JP Beroukhim, R Hahn, WC AF Hagerstrand, Daniel Tong, Alexander Schumacher, Steven E. Ilic, Nina Shen, Rhine R. Cheung, Hiu Wing Vazquez, Francisca Shrestha, Yashaswi Kim, So Young Giacomelli, Andrew O. Rosenbluh, Joseph Schinzel, Anna C. Spardy, Nicole A. Barbie, David A. Mermel, Craig H. Weir, Barbara A. Garraway, Levi A. Tamayo, Pablo Mesirov, Jill P. Beroukhim, Rameen Hahn, William C. TI Systematic Interrogation of 3q26 Identifies TLOC1 and SKIL as Cancer Drivers SO CANCER DISCOVERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; TRANSLATION INITIATION; MESENCHYMAL TRANSITION; ENDOPLASMIC-RETICULUM; HEPATITIS-C; PROTEIN; EXPRESSION; GENES; PROGRESSION; LANDSCAPE AB 3q26 is frequently amplified in several cancer types with a common amplified region containing 20 genes. To identify cancer driver genes in this region, we interrogated the function of each of these genes by loss-and gain-of-function genetic screens. Specifically, we found that TLOC1 (SEC62) was selectively required for the proliferation of cell lines with 3q26 amplification. Increased TLOC1 expression induced anchorage-independent growth, and a second 3q26 gene, SKIL (SNON), facilitated cell invasion in immortalized human mammary epithelial cells. Expression of both TLOC1 and SKIL induced subcutaneous tumor growth. Proteomic studies showed that TLOC1 binds to DDX3X, which is essential for TLOC1-induced transformation and affected protein translation. SKIL induced invasion through upregulation of SLUG (SNAI2) expression. Together, these studies identify TLOC1 and SKIL as driver genes at 3q26 and more broadly suggest that cooperating genes may be coamplified in other regions with somatic copy number gain. SIGNIFICANCE: These studies identify TLOC1 and SKIL as driver genes in 3q26. These observations provide evidence that regions of somatic copy number gain may harbor cooperating genes of different but complementary functions. (C) 2013 AACR. C1 [Hagerstrand, Daniel; Tong, Alexander; Ilic, Nina; Shen, Rhine R.; Cheung, Hiu Wing; Vazquez, Francisca; Shrestha, Yashaswi; Kim, So Young; Giacomelli, Andrew O.; Rosenbluh, Joseph; Schinzel, Anna C.; Spardy, Nicole A.; Barbie, David A.; Mermel, Craig H.; Garraway, Levi A.; Beroukhim, Rameen; Hahn, William C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Schumacher, Steven E.; Beroukhim, Rameen] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Canc Biol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Garraway, Levi A.; Beroukhim, Rameen; Hahn, William C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Canc Genome Discovery,Dana Farber Canc Inst, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Schumacher, Steven E.; Cheung, Hiu Wing; Vazquez, Francisca; Shrestha, Yashaswi; Rosenbluh, Joseph; Barbie, David A.; Mermel, Craig H.; Weir, Barbara A.; Garraway, Levi A.; Tamayo, Pablo; Mesirov, Jill P.; Beroukhim, Rameen; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Kim, So Young] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM william_hahn@dfci.harvard.edu RI Schumacher, Steven/E-9821-2013; Hagerstrand, Daniel/D-1584-2014 OI Schumacher, Steven/0000-0002-6819-5647; Hagerstrand, Daniel/0000-0001-7270-0776 FU NIH/National Cancer Institute (NCI) [R01 CA130988, RC2 CA148268, U54 CA112962]; Sweden-America Foundation; Ernst O. Ek Fund FX This work was supported in part by NIH/National Cancer Institute (NCI) grants R01 CA130988 (to W.C. Hahn), RC2 CA148268 (to W.C. Hahn), and U54 CA112962 (to W.C. Hahn); the Sweden-America Foundation (to D. Hagerstrand), and the Ernst O. Ek Fund (to D. Hagerstrand). NR 53 TC 14 Z9 15 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD SEP PY 2013 VL 3 IS 9 BP 1044 EP 1057 DI 10.1158/2159-8290.CD-12-0592 PG 14 WC Oncology SC Oncology GA 215YH UT WOS:000324246600024 PM 23764425 ER PT J AU Song, MY Zhang, XH Wu, KN Ogino, S Fuchs, CS Giovannucci, EL Chan, AT AF Song, Mingyang Zhang, Xuehong Wu, Kana Ogino, Shuji Fuchs, Charles S. Giovannucci, Edward L. Chan, Andrew T. TI Plasma Adiponectin and Soluble Leptin Receptor and Risk of Colorectal Cancer: A Prospective Study SO CANCER PREVENTION RESEARCH LA English DT Article ID PHYSICAL-ACTIVITY QUESTIONNAIRE; MOLECULAR-WEIGHT ADIPONECTIN; COLON-CANCER; POSTMENOPAUSAL WOMEN; METABOLIC SYNDROME; SERUM ADIPONECTIN; ADIPOSE-TISSUE; NURSES HEALTH; IN-VITRO; REPRODUCIBILITY AB Adipokines are adipocyte-secreted hormones that may mediate the etiologic link between obesity and colorectal cancer; however, the evidence from large prospective studies is limited. We prospectively evaluated the association of plasma adiponectin and soluble leptin receptor (sOB-R) with colorectal cancer risk within the Nurses' Health Study (1990-2008) and the Health Professionals Follow-up Study (1994-2008) among 616 incident colorectal cancer cases and 1,205 controls selected using risk-set sampling and matched on age and date of blood draw. In unconditional logistic regression with adjustment for matching factors and multiple risk factors, plasma adiponectin was significantly associated with reduced risk of colorectal cancer among men, but not among women. Compared with men in the lowest quartile of adiponectin, men in the highest quartile had a relative risk (RR) for colorectal cancer of 0.55 [ 95% confidence interval (CI), 0.35-0.86; P-trend = 0.02]. The corresponding RR in women was 0.96 (95% CI, 0.67-1.39; P-trend = 0.74). Plasma sOB-R was not associated with overall colorectal cancer risk in either men or women. A significant heterogeneity was noted in the association between sOB-R and colorectal cancer by subsite in women (P-heterogeneity = 0.004); sOB-R was significantly associated with increased risk of rectal cancer but not colon cancer. These findings support a role for adiponectin in colorectal carcinogenesis in men. Further studies are warranted to confirm these associations and elucidate potential underlying mechanisms. Cancer Prev Res; 6(9); 875-85. (C) 2013 AACR. C1 [Song, Mingyang; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02114 USA. [Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. [Zhang, Xuehong; Ogino, Shuji; Fuchs, Charles S.; Giovannucci, Edward L.; 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. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA 02114 USA. RP Chan, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org RI Song, Mingyang/M-6701-2013 OI Song, Mingyang/0000-0002-1324-0316 FU U.S. NIH [P01 CA87969, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA151993, K24 DK098311, R01 CA137178] FX This work was supported by U.S. NIH grants [P01 CA87969 (to S. E. Hankinson), P01 CA55075 (to W. C. Willett), UM1 CA167552 (to W. C. Willett), P50 CA127003 (to C. S. Fuchs), R01 CA151993 (to S. Ogino), K24 DK098311 (to A. T. Chan) and R01 CA137178 (to A. T. Chan)]. A. T. Chan is a Damon Runyon Clinical Investigator. NR 56 TC 27 Z9 29 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD SEP PY 2013 VL 6 IS 9 BP 875 EP 885 DI 10.1158/1940-6207.CAPR-13-0169 PG 11 WC Oncology SC Oncology GA 214XH UT WOS:000324171000001 PM 23872505 ER PT J AU Natarajan, S Li, YC Miller, EE Shih, DJ Taylor, MD Stearns, TM Bronson, RT Ackerman, SL Yoon, JK Yun, K AF Natarajan, Sivaraman Li, Yaochen Miller, Emily E. Shih, David J. Taylor, Michael D. Stearns, Timothy M. Bronson, Roderick T. Ackerman, Susan L. Yoon, Jeong K. Yun, Kyuson TI Notch1-Induced Brain Tumor Models the Sonic Hedgehog Subgroup of Human Medulloblastoma SO CANCER RESEARCH LA English DT Article ID NEURAL STEM-CELLS; TRANSCRIPTIONAL REGULATION; NOTCH; PATHWAY; ACTIVATION; GROWTH; PROLIFERATION; LEUKEMIA; DIFFERENTIATION; INHIBITION AB While activation of the Notch pathway is observed in many human cancers, it is unknown whether elevated Notch1 expression is sufficient to initiate tumorigenesis in most tissues. To test the oncogenic potential of Notch1 in solid tumors, we expressed an activated form of Notch1 (N1ICD) in the developing mouse brain. N1ICD; hGFAP-cre mice were viable but developed severe ataxia and seizures, and died by weaning age. Analysis of transgenic embryo brains revealed that N1ICD expression induced p53-dependent apoptosis. When apoptosis was blocked by genetic deletion of p53, 30% to 40% of N1ICD; GFAP-cre;p53(+/-) and N1ICD; GFAP-cre; p53(-/-) mice developed spontaneous medulloblastomas. Interestingly, N1ICD-induced medulloblastomas most closely resembled the sonic hedgehog subgroup of human medulloblastoma at the molecular level. Surprisingly, N1ICD-induced tumors do not maintain high levels of the Notch pathway gene expression, except for Notch2, showing that initiating oncogenic events may not be decipherable by analyzing growing tumors in some cases. In summary, this study shows that Notch1 has an oncogenic potential in the brain when combined with other oncogenic hits, such as p53 loss, and provides a novel mouse model of medulloblastoma. Cancer Res; 73(17); 5381-90. (C) 2013 AACR. C1 [Natarajan, Sivaraman; Li, Yaochen; Miller, Emily E.; Stearns, Timothy M.; Ackerman, Susan L.; Yun, Kyuson] Jackson Lab, Bar Harbor, ME 04609 USA. [Ackerman, Susan L.] Howard Hughes Med Inst, Scarborough, ME USA. [Yoon, Jeong K.] Maine Med Ctr, Res Inst, Scarborough, ME USA. [Bronson, Roderick T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shih, David J.; Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada. RP Yun, K (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM Kyuson.yun@jax.org RI Shih, David/H-3186-2011 OI Shih, David/0000-0002-9802-4937 FU Maine Cancer Foundation; TJL Cancer Center [CA034196] FX This work was supported in part by the Maine Cancer Foundation and TJL Cancer Center Support grant (CA034196; K. Yun). NR 43 TC 7 Z9 7 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2013 VL 73 IS 17 BP 5381 EP 5390 DI 10.1158/0008-5472.CAN-13-0033 PG 10 WC Oncology SC Oncology GA 214ER UT WOS:000324114400010 PM 23852537 ER PT J AU Stroopinsky, D Rosenblatt, J Ito, K Mills, H Yin, L Rajabi, H Vasir, B Kufe, T Luptakova, K Arnason, J Nardella, C Levine, JD Joyce, RM Galinsky, I Reiter, Y Stone, RM Pandolfi, PP Kufe, D Avigan, D AF Stroopinsky, Dina Rosenblatt, Jacalyn Ito, Keisuke Mills, Heidi Yin, Li Rajabi, Hasan Vasir, Baldev Kufe, Turner Luptakova, Katarina Arnason, Jon Nardella, Caterina Levine, James D. Joyce, Robin M. Galinsky, Ilene Reiter, Yoram Stone, Richard M. Pandolfi, Pier Paolo Kufe, Donald Avigan, David TI MUC1 Is a Potential Target for the Treatment of Acute Myeloid Leukemia Stem Cells SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; TRANSCRIPTION FACTOR; INITIATING CELLS; CANCER CELLS; ONCOPROTEIN; EXPRESSION; AML; NUCLEOPHOSMIN; HETEROGENEITY; ACTIVATION AB Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34(+)/lineage(-)/CD38 cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34(+) populations as similar results were obtained with leukemic cells from patients with CD34(-) disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1(high)) led to development of leukemia in NOD-SCID IL2Rgamma(nul)l (NSG) immunodeficient mice. In contrast, MUC1(low) cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication. (C) 2013 AACR. C1 [Stroopinsky, Dina; Rosenblatt, Jacalyn; Ito, Keisuke; Mills, Heidi; Kufe, Turner; Luptakova, Katarina; Arnason, Jon; Nardella, Caterina; Levine, James D.; Joyce, Robin M.; Pandolfi, Pier Paolo; Avigan, David] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Yin, Li; Rajabi, Hasan; Vasir, Baldev; Galinsky, Ilene; Stone, Richard M.; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Reiter, Yoram] Technion Israel Inst Technol, Haifa, Israel. RP Avigan, D (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM davigan@bidmc.harvard.edu FU Lady Tata Memorial Trust; Leukemia Lymphoma Society [6074-09, 6226-12]; National Cancer Institute [CA42802, CA100707] FX This study was supported in part by research funding from Lady Tata Memorial Trust (D. Stroopinsky) and grants from the Leukemia Lymphoma Society (6074-09 and 6226-12) and the National Cancer Institute (CA42802, CA100707). NR 34 TC 19 Z9 19 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2013 VL 73 IS 17 BP 5569 EP 5579 DI 10.1158/0008-5472.CAN-13-0677 PG 11 WC Oncology SC Oncology GA 214ER UT WOS:000324114400026 PM 23867470 ER PT J AU Marneros, AG AF Marneros, Alexander G. TI NLRP3 Inflammasome Blockade Inhibits VEGF-A-Induced Age-Related Macular Degeneration SO CELL REPORTS LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; OXIDATIVE-STRESS; CHOROIDAL NEOVASCULARIZATION; BASAL DEPOSITS; MACULOPATHY; DRUSEN; MICE; ACTIVATION; EXPRESSION; CELLS AB The NLRP3 inflammasome is activated in age-related macular degeneration (AMD), but it remains unknown whether its activation contributes to AMD pathologies. VEGF-A is increased in neovascular ("wet") AMD, but it is not known whether it plays a role in inflammasome activation, whether an increase of VEGF-A by itself is sufficient to cause neovascular AMD and whether it can contribute to nonexudative ("dry") AMD that often co-occurs with the neovascular form. Here, it is shown that an increase in VEGF-A results in NLRP3 inflammasome activation and is sufficient to cause both forms of AMD pathologies. Targeting NLRP3 or the inflammasome effector cytokine IL-1 beta inhibits but does not prevent VEGF-A-induced AMD pathologies, whereas targeting IL-18 promotes AMD. Thus, increased VEGF-A provides a unifying pathomechanism for both forms of AMD; combining therapeutic inhibition of both VEGF-A and IL-1 beta or the NLRP3 inflammasome is therefore likely to suppress both forms of AMD. C1 [Marneros, Alexander G.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Marneros, Alexander G.] Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA. RP Marneros, AG (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM amarneros@partners.org FU NEI [R01-EY019297] FX I would like to thank Drs. Andras Nagy, Lucile Miquerol, and Annette Damert for providing VEGF-Ahyper and VEGF-Ahypo mice and Dr. Napoleone Ferrara for providing VEGF-Afl/fl mice. This work was supported by a grant to A. G. M. from the NEI R01-EY019297. NR 40 TC 33 Z9 35 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD SEP PY 2013 VL 4 IS 5 BP 945 EP 958 DI 10.1016/j.celrep.2013.08.002 PG 14 WC Cell Biology SC Cell Biology GA 216LZ UT WOS:000324286300012 PM 24012762 ER PT J AU Yuan, KY Sun, Y Zhou, T McDonald, J Chen, YB AF Yuan, Kaiyu Sun, Yong Zhou, Tong McDonald, Jay Chen, Yabing TI PARP-1 Regulates Resistance of Pancreatic Cancer to TRAIL Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID LIGAND-INDUCED APOPTOSIS; FAS-MEDIATED APOPTOSIS; NF-KAPPA-B; POLY(ADP-RIBOSE) POLYMERASE; IN-VITRO; MONOCLONAL-ANTIBODY; INHIBITORY PROTEIN; DNA-DAMAGE; CELL-LINES; MECHANISMS AB Purpose: Activating extrinsic apoptotic pathways targeting death receptors (DR) using agonistic antibodies or TNF-related apoptosis-inducing ligand (TRAIL) is promising for cancer therapy. However, most pancreatic cancers are resistant to TRAIL therapy. The present studies aimed to identify combination therapies that enhance the efficacy of TRAIL therapy and to investigate the underlying mechanisms. Experimental Design: A xenograft model in nude mice was used to determine pancreatic cancer tumorigenesis and therapeutic efficacy of TRA-8, a monoclonal agonistic antibody for DR5. Pancreatic cancer cells were used to characterize mechanisms underlying PARP-1 regulation of TRA-8-induced apoptosis in vitro. Results: PARP-1 was found highly expressed in the TRA-8-resistant PANC-1 and Suit-2 cells, compared with TRA-8-sensitive BxPc-3 and MiaPaca-2. Inhibition of PARP-1 with a pharmacologic inhibitor sensitized PANC-1 and Suit2 cells to TRA-8-induced apoptosis in a dose-dependent manner. Furthermore, siRNAs specifically knocking down PARP-1 markedly enhanced TRA-8-induced apoptosis in vitro and augmented the efficacy of TRA-8 therapy on tumorigenesis in vivo. PARP-1 knockdown increased TRA-8-induced activation of caspase-8 in the death-induced signaling complex (DISC). Immunoprecipitation with DR5 antibody identified the recruitment of PARP-1 and PARP-1-mediated protein poly-ADP-ribosylation (pADPr) modification in the DR5-associated DISC. Further characterization revealed that PARP-1-mediated pADPr modification of caspase-8 inhibited caspase-8 activation, which may contribute to its function in regulating TRA-8 resistance. Conclusions: Our studies provide molecular insights into a novel function of PARP-1 in regulating the extrinsic apoptosis machinery and also support interventions combining PARP-1 inhibitors with DR agonists for pancreatic cancer therapy. (C)2013 AACR. C1 [Yuan, Kaiyu; Sun, Yong; McDonald, Jay; Chen, Yabing] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhou, Tong] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [McDonald, Jay; Chen, Yabing] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Chen, YB (reprint author), Univ Alabama Birmingham, Dept Pathol, 614 Shelby Res Bldg,1825 Univ Blvd, Birmingham, AL 35294 USA. EM ybchen@uab.edu FU UAB Department of Pathology; VA Merit Review Award; NIH [P50CA101955] FX This work was supported in part by UAB Department of Pathology start-up funds (to Y. Chen) and a VA Merit Review Award (to J.M. McDonald). T. Zhou was support by a NIH grant P50CA101955. NR 49 TC 22 Z9 22 U1 2 U2 11 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 1 PY 2013 VL 19 IS 17 BP 4750 EP 4759 DI 10.1158/1078-0432.CCR-13-0516 PG 10 WC Oncology SC Oncology GA 213ZE UT WOS:000324098400023 PM 23833311 ER PT J AU Vickers, MM Al-Harbi, H Choueiri, TK Kollmannsberger, C North, S MacKenzie, M Knox, JJ Rini, BI Heng, DYC AF Vickers, Michael M. Al-Harbi, Hulayel Choueiri, Toni K. Kollmannsberger, Christian North, Scott MacKenzie, Mary Knox, Jennifer J. Rini, Brian I. Heng, Daniel Y. C. TI Prognostic Factors of Survival for Patients With Metastatic Renal Cell Carcinoma With Brain Metastases Treated With Targeted Therapy: Results From the International Metastatic Renal Cell Carcinoma Database Consortium SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Brain metastases; Mammalian targets of rapamycin; Renal cell carcinoma; Targeted therapy; Vascular endothelial growth factor ID INTERFERON-ALPHA; TRIAL; SORAFENIB; SUNITINIB AB Outcomes and prognosis of patients with brain metastases from advanced renal cell carcinoma are not well characterized in the targeted-therapy era. This retrospective series of 106 patients with metastatic renal cell carcinoma and brain metastases revealed that the Karnofsky performance status at the start of therapy, diagnosis to treatment time, and number of brain metastases are prognostic factors for overall survival in this patient population. Background: The outcomes and prognosis of patients with brain metastases from advanced renal cell carcinoma (RCC) are not well characterized in the targeted-therapy era. Methods: Data from patients with metastatic RCC (mRCC) and brain metastases treated with targeted therapy were collected through the International Metastatic Renal Cell Carcinoma Database Consortium from 7 cancer centers. Results: Overall, 106 (15%) of 705 patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-vascular endothelial growth factor therapy, and the rest developed metastases during follow-up. Of the patients with brain metastases, 12%, 42% and 29% were in the favorable, intermediate, and poor prognosis groups, respectively, per the Heng criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 37% had a Karnofsky performance status (KPS) <80%, and 80% had neurologic symptoms at presentation. The median largest size and number of brain metastases was 1.8 cm (range, 0.2-6.6 cm) and one (range, 1 to innumerable), respectively. The patients were treated with sunitinib (n = 77), sorafenib (n = 23), bevacizumab (n = 5), and temsirolimus (n = 1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). On multivariable analysis, KPS < 80%, diagnosis to treatment with targeted therapy < 1 year, and a higher number of brain metastases (>4) was associated with worse survival from the time of diagnosis with brain metastases. Conclusions: Patients with brain metastases from RCC are unlikely to be in the favorable risk group. KPS at the start of therapy, diagnosis to treatment time, and the number of brain metastases are prognostic factors for overall survival. (C) 2013 Elsevier Inc. All rights reserved. C1 [Vickers, Michael M.; Al-Harbi, Hulayel; Heng, Daniel Y. C.] Tom Baker Canc Clin, Dept Oncol, Calgary, AB T2N 4N2, Canada. [Choueiri, Toni K.] Dana Farber Harvard Canc Ctr, Div Solid Tumor Oncol, Boston, MA USA. [Kollmannsberger, Christian] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [North, Scott] Cross Canc Inst, Dept Oncol, Edmonton, AB T6G 1Z2, Canada. [MacKenzie, Mary] London Reg Hlth Ctr, Dept Oncol, London, ON, Canada. [Knox, Jennifer J.] Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. [Rini, Brian I.] Cleveland Clin, Taussig Canc Ctr, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA. RP Vickers, MM (reprint author), Tom Baker Canc Clin, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM michael.vickers@albertahealthservices.ca FU Pfizer; Novartis; GlaxoSmithKline FX T. K. Choueiri has received research funding from Pfizer and has a consultant or advisory role at Aveo, Pfizer, Novartis, GlaxoSmithKline, Genentech, and Bayer/Onyx. C. Kollmannsberger has a consultant or advisory role at and has received honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. S. North has a consultant or advisory role at Pfizer, Novartis, Bayer, and GlaxoSmithKline. M. MacKenzie has a consultant or advisory role, and has received research funding from Pfizer and Novartis. J. J. Knox has a consultant or advisory role, and has received research funding from Pfizer. B. I. Rini has a consultant or advisory role at Pfizer, GlaxoSmithKline, Aveo, and Bayer/Onyx, and has received research funding from GlaxoSmithKline and Pfizer. D. Y. C. Heng has received research funding from Pfizer and has a consultant or advisory role at Pfizer, Novartis, GlaxoSmithKline, Aveo, Genentech, and Bayer/Onyx. All other authors have stated that they have no conflicts of interest. NR 19 TC 15 Z9 15 U1 0 U2 6 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2013 VL 11 IS 3 BP 311 EP 315 DI 10.1016/j.clgc.2013.04.012 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 215ZX UT WOS:000324251400014 PM 23684422 ER PT J AU Maughan, BL Agarwal, N Hussain, SA Boucher, KM Von Der Maase, H Kaufman, DS Lorusso, V Moore, MJ Galsky, MD Sonpavde, G AF Maughan, Benjamin L. Agarwal, Neeraj Hussain, Syed A. Boucher, Kenneth M. Von Der Maase, Hans Kaufman, Donald S. Lorusso, Vito Moore, Malcolm J. Galsky, Matthew D. Sonpavde, Guru TI Pooled Analysis of Phase II Trials Evaluating Weekly or Conventional Cisplatin as First-Line Therapy for Advanced Urothelial Carcinoma SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Weekly; Fractionated; Conventional; Cisplatin; Toxicities; Response rate; Advanced urothelial carcinoma ID TRANSITIONAL-CELL CARCINOMA; GEMCITABINE PLUS CISPLATIN; METASTATIC BLADDER-CANCER; LONG-TERM-SURVIVAL; RADICAL CYSTECTOMY; CHEMOTHERAPY; METHOTREXATE; VINBLASTINE; DOXORUBICIN; COMBINATION AB In a pooled analysis of phase II trials, gemcitabine combined with day 1 cisplatin (GC) or weekly cisplatin (wGC) yielded similar outcomes and toxicities in advanced urothelial carcinoma. Considering the feasibility of wGC in patients with renal dysfunction, a prospective comparison of GC and wGC might facilitate a broad chemotherapy backbone and accelerate the development of combinations with biological agents. Background: Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC and wGC to compare efficacy and safety. Patients and Methods: Two trials of wGC and 3 trials of GC were identified. Because the data were not derived from randomized trials, GC and wGC were not formally compared, and exact 95% quasi-binomial confidence intervals (CI), for response rates and grade >=(3) toxicities were calculated. Results: The 95% CI overlapped, suggesting agreement between wGC and GC. No clear difference in response rates and grade >= 3 toxicities between GC and wGC were observed. Conclusion: Gemcitabine combined with day 1 cisplatin and wGC yielded similar responses and grade >= 3 toxicities in advanced UC in a hypothesis-generating pooled analysis of phase II trials. Considering the probable lower nephrotoxicity of fractionated cisplatin, prospective evaluation of wGC might be warranted across cisplatin-eligible and -ineligible patients to develop a single chemotherapy template for the development of combinations with biological agents in a broad population of patients. (C) 2013 Elsevier Inc. All rights reserved. C1 [Maughan, Benjamin L.; Agarwal, Neeraj; Boucher, Kenneth M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Hussain, Syed A.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Von Der Maase, Hans] Rigshosp, Copenhagen Univ Hosp, DK-2100 Copenhagen, Denmark. [Von Der Maase, Hans] Aarhus Univ Hosp, Copenhagen, Denmark. [Kaufman, Donald S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaufman, Donald S.] Harvard Univ, Sch Med, Boston, MA USA. [Lorusso, Vito] Natl Canc Res Ctr, Ist Tumori Giovanni Paolo II, Bari, Italy. [Moore, Malcolm J.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Galsky, Matthew D.] Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA. [Sonpavde, Guru] Univ Alabama Birmingham, Birmingham UAB Comprehens Canc Ctr, Birmingham, AL USA. RP Sonpavde, G (reprint author), UAB Comprehens Canc Ctr, 1824 6th Ave South,WTI 520A, Birmingham, AL 35294 USA. EM gsonpavde@uabmc.edu OI Boucher, Kenneth/0000-0003-2833-0127 NR 29 TC 2 Z9 2 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2013 VL 11 IS 3 BP 316 EP 320 DI 10.1016/j.clgc.2012.12.007 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 215ZX UT WOS:000324251400015 PM 23332638 ER PT J AU Rojan, A Funches, R Regan, MM Gulley, JL Bubley, GJ AF Rojan, Adam Funches, Renee Regan, Meredith M. Gulley, James L. Bubley, Glenn J. TI Dramatic and Prolonged PSA Response After Retreatment With a PSA Vaccine SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Immunologic response; PROSTVAC-VF; Revaccination ID RESISTANT PROSTATE-CANCER; TRIAL; IMMUNOTHERAPY C1 [Rojan, Adam; Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Funches, Renee] Midatlantic Permanente Med Grp, Dept Hematol Oncol, Washington, DC USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bubley, GJ (reprint author), Beth Israel Deaconess Med Ctr, CLS 449,330 Brookline Ave, Boston, MA 02215 USA. EM gbubley@bidmc.harvard.edu RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 11 TC 2 Z9 2 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD SEP PY 2013 VL 11 IS 3 BP 362 EP 364 DI 10.1016/j.clgc.2013.01.003 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 215ZX UT WOS:000324251400024 PM 23791437 ER PT J AU Schestatsky, P Simis, M Freeman, R Pascual-Leone, A Fregni, F AF Schestatsky, Pedro Simis, Marcel Freeman, Roy Pascual-Leone, Alvaro Fregni, Felipe TI Non-invasive brain stimulation and the autonomic nervous system SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Non-invasive brain stimulation; Transcranial magnetic stimulation; Transcranial direct current stimulation; Autonomic nervous system; Systematic review ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; HEART-RATE-VARIABILITY; PREFRONTAL CORTEX; ELECTRICAL-STIMULATION; ELECTRODERMAL ACTIVITY; SYMPATHETIC ACTIVITY; TACHYCARDIA SYNDROME; PARKINSONS-DISEASE; HEALTHY-VOLUNTEERS AB Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive methods of brain stimulation (NIBS) that can induce significant effects on cortical and subcortical neural networks. Both methods are relatively safe if appropriate guidelines are followed, and both can exert neuromodulatory effects that may be applied to the investigation of the autonomic nervous system (ANS). In addition, ANS measures can shed important light onto the neurobiologic mechanisms of NIBS. Here we present a systematic review on studies testing NIBS and ANS simultaneously. We structure our findings into four broad (not mutually exclusive) categories: (i) studies in which ANS function was modified by NIBS versus those in which it was not; (ii) studies in which NIBS was used to understand ANS function, (iii) studies in which ANS was used to understand NIBS mechanisms and (iv) NIBS/ANS studies conducted in healthy subjects versus those in patients with neuropsychiatric diseases. Forty-four articles were identified and no conclusive evidence of the effects of NIBS on ANS was observed, mainly because of the heterogeneity of included studies. Based on a comprehensive summary of this literature we propose how NIBS might be further developed to enhance our understanding of the cortical mechanisms of autonomic regulation and perhaps to modulate autonomic activity for therapeutic purposes. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Schestatsky, Pedro] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Med, BR-90046900 Porto Alegre, RS, Brazil. [Schestatsky, Pedro] Univ Fed Rio Grande do Sul, Dept Internal Med, BR-90046900 Porto Alegre, RS, Brazil. [Schestatsky, Pedro; Simis, Marcel; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat,Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Schestatsky, Pedro; Simis, Marcel; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Simis, Marcel] Santa Casa Sao Paulo Med Sch, Div Neurol, Sao Paulo, Brazil. [Freeman, Roy] Beth Israel Deaconess Med Ctr, Dept Neurol, Auton & Peripheral Nerve Lab, Boston, MA USA. [Pascual-Leone, Alvaro; Fregni, Felipe] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat,Behav, Boston, MA 02114 USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat, 125 Nashua St 727, Boston, MA 02114 USA. EM fregni.felipe@mgh.harvard.edu FU CAPES-Brazil [BEX 9605/11-5, 9722/11-4] FX The authors are grateful to Olivia Tousignant-Pienkos for her assistance during the data collection, to Fernanda Queiros for her assistance in data analysis and to Deborah Nadler for her assistance in copyediting this manuscript. We also want to thanks the grant from CAPES-Brazil: BEX 9605/11-5 (PS) and 9722/11-4 (MS). NR 100 TC 14 Z9 14 U1 1 U2 21 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD SEP PY 2013 VL 124 IS 9 BP 1716 EP 1728 DI 10.1016/j.clinph.2013.03.020 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 213AV UT WOS:000324026200005 PM 23684898 ER PT J AU Chen, L Mao, JR AF Chen, Lucy Mao, Jianren TI Update on Neuropathic Pain Treatment: Ion Channel Blockers and Gabapentinoids SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Ion channel blockers; Gabapentinoids; Neuropathic pain; Chronic pain; Sodium channel blockers ID DIABETIC PERIPHERAL NEUROPATHY; RANDOMIZED CONTROLLED-TRIAL; LIDOCAINE PATCH 5-PERCENT; PLACEBO-CONTROLLED TRIAL; ROUTINE MEDICAL-PRACTICE; SPINAL-CORD-INJURY; LOW-BACK-PAIN; POSTHERPETIC NEURALGIA; DOUBLE-BLIND; TRIGEMINAL NEURALGIA AB Neuropathic pain is a debilitating chronic pain condition, which remains difficult to treat. The current main-stays of treatment include physical therapy, interventional procedures and medications. Among medications, ion channel blockers and gabapentinoids are the 2 classes of drugs commonly used to treat neuropathic pain. It has been suggested that these medications may be useful to treat a variety of neuropathic pain conditions. This article provides several updates on the utility of both ion channel blockers and gabapentinoids for the treatment of neuropathic pain. C1 [Chen, Lucy; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. EM jmao@partners.org NR 103 TC 5 Z9 5 U1 2 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD SEP PY 2013 VL 17 IS 9 AR 359 DI 10.1007/s11916-013-0359-2 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 215RR UT WOS:000324228500003 PM 23888370 ER PT J AU Schrag, D AF Schrag, Deborah TI Evolving Role of Neoadjuvant Therapy in Rectal Cancer SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Article DE Locally advanced rectal cancer; Neoadjuvant chemotherapy; Chemoradiation; Total mesorectal excision; Overtreatment ID PHASE-III TRIAL; POSTOPERATIVE ADJUVANT CHEMOTHERAPY; SHORT-COURSE RADIOTHERAPY; COLORECTAL-CANCER; RANDOMIZED-TRIAL; COLON-CANCER; FOLLOW-UP; PREOPERATIVE RADIOTHERAPY; ASPIRIN USE; SURGERY AB Management of locally advanced rectal cancer is complex because curative treatment routinely involves administration of surgery, chemotherapy, and radiation. Optimal treatment delivery sequencing and timing are challenging, and moreover, there is considerable heterogeneity in risk based on rectal tumor location, extent, and nodal involvement. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Currently, the standard approach to management of locally advanced (T3 or T2) rectal cancer involves careful staging with a pelvic MRI and proctoscopic evaluation by a surgeon experienced in total mesorectal excision. MRI can help to distinguish between patients in low-, intermediate-, and high-risk categories. Low-risk tumors have no evidence of either extramural spread or nodal involvement and proximal location in the rectum. For such patients, R0 resection is almost always possible and immediate surgery often is reasonable. In the minority of cases where unanticipated lymph node involvement is detected at surgical pathology, postoperative radiation can be administered. Patients who opt for up-front rectal surgery need to understand that although there is a chance that radiation can be avoided, if it is necessary, it is less well tolerated when administered postoperatively. Initial surgical treatment should be reserved for low-risk patients for whom imaging indicates and multidisciplinary team members feel is able to undergo an R0 resection with low chance for regional spread of disease. For patients with high-risk disease based on distal tumor location requiring an APR, threatened radial margins, or T4 tumors, preoperative chemoradiation is essential. Indeed, this approach increases the likelihood of complete surgical resection with negative margins. For some high-risk patients, for example those with T4 or bulky nodal disease, preoperative systemic therapy followed by preoperative chemoradiation and then surgery may be optimal. The feasibility of this approach is well established based on nonrandomized trials, but it has not been evaluated in a randomized study. Preoperative administration of systemic therapy can achieve clinical downstaging, optimize rates of sphincter preservation, and establish tumor responsiveness, which may be valuable for incorporation into future treatment decisions. For patients with intermediate-risk T3 rectal cancers, for example, a cT3N1 tumor 7 cm from the anal verge with two to three regional lymph nodes in the 7-mm range, we encourage participation in the PROSPECT randomized trial, which is now open and accruing at numerous centers in North America, and shortly in Europe and South America as well. This study will determine in the era of optimal imaging, surgical technique, and better systemic chemotherapy, whether pelvic radiation remains an essential component of curative treatment. The PROSPECT study uses chemoradiation selectively rather than automatically and customizes subsequent treatment based on response to neoadjuvant FOLFOX. Clinical trials with interventions that tailor treatment to more precisely defined clinical subgroups based on both initial features and tumor responsiveness are expected to become the norm. Although this trend is likely to make clinical trial design more complex, customized treatment strategies are likely to achieve the optimal balance between under- and overtreatment and will address the heterogeneity of both tumor biology and disease presentation. For now, treatment for a patient with clinical T3N1 tumor in the mid rectum consists of the following components:Neoadjvuant chemoradiation with either 5-fluorouracil or capecitabine as sensitizing therapy. Low anterior resection with total mesorectal excision. Typically a temporary diverting ostomy is required. Postoperative administration of adjuvant systemic therapy, 8 cycles of FOLFOX is appropriate, although oxaliplatin should be omitted for early signs of peripheral neuropathy or on the basis of age/comorbidity. Although this is the current care standard, there is concern that such extensive treatment is not necessary for all patients to prevent local recurrence and to optimize cure. To determine if therapy can be streamlined, participation in PROSPECT or other clinical trials asking compelling clinical questions is a priority. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Schrag, D (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM Deb_schrag@dfci.harvard.edu NR 37 TC 12 Z9 13 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 EI 1534-6277 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD SEP PY 2013 VL 14 IS 3 BP 350 EP 364 DI 10.1007/s11864-013-0242-8 PG 15 WC Oncology SC Oncology GA 215XT UT WOS:000324245100005 PM 23828092 ER PT J AU Faris, JE Ryan, DP AF Faris, Jason E. Ryan, David P. TI Controversy and Consensus on the Management of Patients With Pseudomyxoma Peritonei SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Article DE Pseudomyxoma peritonei; Carcinomatosis; Cytoreduction; Heated intraperitoneal chemotherapy ID HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; APPENDICEAL MUCINOUS NEOPLASMS; CYTOREDUCTIVE SURGERY; COLORECTAL-CANCER; CLINICOPATHOLOGICAL ANALYSIS; SYSTEMIC CHEMOTHERAPY; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; CARCINOMATOSIS; ORIGIN AB Pseudomyxoma peritonei and peritoneal carcinomatosis derived from appendiceal epithelial tumors are controversial entities from classification to treatment. For the former entity, multiple classification systems have been attempted to distinguish indolent from more aggressive subtypes. The treatment of the low grade variants is managed with serial cytoreduction surgery, with data indicating possible, but unproven, benefit from heated intraperitoneal chemotherapy (HIPEC). There is no consensus on the role of cytoreduction and HIPEC for the management of the more aggressive histologic variants and peritoneal carcinomatosis. Currently, we believe systemic chemotherapy is the standard of care for patients with the high grade variants and peritoneal carcinomatosis. C1 [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7E 55 Fruit St, Boston, MA 02114 USA. EM DPRYAN@PARTNERS.ORG NR 37 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD SEP PY 2013 VL 14 IS 3 BP 365 EP 373 DI 10.1007/s11864-013-0240-x PG 9 WC Oncology SC Oncology GA 215XT UT WOS:000324245100006 PM 23934509 ER PT J AU Vaughn, LS Bragg, DC Sharma, N Camargos, S Cardoso, F Patel, RC AF Vaughn, Lauren S. Bragg, D. Cristopher Sharma, Nutan Camargos, Sarah Cardoso, Francisco Patel, Rekha C. TI Effect of dystonia-causing point mutation in PACT on activation of interferon-induced protein kinase PKR SO CYTOKINE LA English DT Meeting Abstract CT Annual Joint Conference of the International-Cytokine-Society and the International-Society-for-Interferon-and-Cytokine-Research CY SEP 29-OCT 03, 2013 CL San Francisco, CA SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Vaughn, Lauren S.; Patel, Rekha C.] Univ S Carolina, Dept Biol, Columbia, SC 29208 USA. [Bragg, D. Cristopher; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Camargos, Sarah; Cardoso, Francisco] Univ Fed Minas Gerais, Dept Internal Med, Belo Horizonte, MG, Brazil. RI Patel, Rekha/M-7123-2015 OI Patel, Rekha/0000-0001-9434-4880 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2013 VL 63 IS 3 SI SI BP 306 EP 307 DI 10.1016/j.cyto.2013.06.271 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 212WO UT WOS:000324013700280 ER PT J AU Nyer, M Farabaugh, A Fehling, K Soskin, D Holt, D Papakostas, GI Pedrelli, P Fava, M Pisoni, A Vitolo, O Mischoulon, D AF Nyer, Maren Farabaugh, Amy Fehling, Kiki Soskin, David Holt, Daphne Papakostas, George I. Pedrelli, Paola Fava, Maurizio Pisoni, Angela Vitolo, Ottavio Mischoulon, David TI RELATIONSHIP BETWEEN SLEEP DISTURBANCE AND DEPRESSION, ANXIETY, AND FUNCTIONING IN COLLEGE STUDENTS SO DEPRESSION AND ANXIETY LA English DT Article DE sleep; depression; anxiety; hopelessness; functioning; quality of life; college students; mental health screening; hyperarousal ID ACADEMIC-PERFORMANCE; UNIVERSITY-STUDENTS; SUICIDAL IDEATION; PUBLIC UNIVERSITY; INSOMNIA; SYMPTOMS; DISORDERS; QUALITY; QUESTIONNAIRE; SATISFACTION AB Background Sleep disturbance (SD) has complex associations with depression, both preceding and following the onset and recurrence of depression. We hypothesized that students with depressive symptoms with SD would demonstrate a greater burden of comorbid psychiatric symptoms and functional impairment compared to students with depressive symptoms without SD. Methods During a mental health screening, 287 undergraduate students endorsed symptoms of depression (Beck Depression Inventory [BDI] 13) and filled out the following self-report measures: demographic questionnaire, BDI, Anxiety Symptom Questionnaireintensity and frequency (ASQ), Beck Hopelessness Scale (BHS), Beck Anxiety Inventory (BAI), Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ), and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ). SD was measured using the BDI sleep item #16 dichotomized (score 0: no SD; or score > 0: some SD). Results Students with depressive symptoms and SD (n = 220), compared to those without SD (n = 67), endorsed significantly more intense and frequent anxiety and poorer cognitive and physical functioning. Students with depressive symptoms with and without SD did not significantly differ in depressive severity, hopelessness, or quality of life. Conclusions College students with depressive symptoms with SD may experience a greater burden of comorbid anxiety symptoms and hyperarousal, and may have impairments in functioning, compared to students with depressive symptoms without SD. These findings require replication. C1 [Nyer, Maren; Farabaugh, Amy; Fehling, Kiki; Soskin, David; Holt, Daphne; Papakostas, George I.; Pedrelli, Paola; Fava, Maurizio; Pisoni, Angela; Vitolo, Ottavio; Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nyer, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM mnyer@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU The Jed Foundation FX Contract grant sponsor: The Jed Foundation. NR 44 TC 16 Z9 17 U1 8 U2 75 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD SEP PY 2013 VL 30 IS 9 BP 873 EP 880 DI 10.1002/da.22064 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 210II UT WOS:000323824300011 PM 23681944 ER PT J AU Brooks-Worrell, B Narla, R Palmer, JP AF Brooks-Worrell, B. Narla, R. Palmer, J. P. TI Islet autoimmunity in phenotypic type 2 diabetes patients SO DIABETES OBESITY & METABOLISM LA English DT Review DE autoimmune disease; autoimmunity; inflammation; islet-reactive T cells; T cells; type 1 diabetes; type 2 diabetes ID GLUTAMIC-ACID DECARBOXYLASE; T-CELL RESPONSES; INSULIN-RESISTANCE; CHRONIC INFLAMMATION; CLINICAL PHENOTYPE; ADULTS LADA; OLDER AGE; LATENT; ANTIBODIES; PROTEINS AB Historically, type 2 diabetes (T2D) was considered a metabolic disease of ageing. However, recent discoveries have demonstrated the role of chronic systemic inflammation in the development of insulin resistance and subsequent progression to T2D. Over the years, investigations into the pathophysiology of T2D have identified the presence of islet-specific T cells and islet autoimmune disease in T2D patients. Moreover, the cell-mediated islet autoimmunity has also been correlated with the progressive loss of beta-cell function associated with T2D disease pathogenesis. In this manuscript, the involvement of cell-mediated islet autoimmune disease in the progression of T2D disease and the similarities in islet-specific T-cell reactivity between type 1 diabetes (T1D) and T2D are discussed. C1 [Brooks-Worrell, B.; Palmer, J. P.] Univ Washington, Dept Med, Seattle, WA USA. [Narla, R.; Palmer, J. P.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. RP Brooks-Worrell, B (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM bbrooks@u.washington.edu FU NIDDK NIH HHS [P30 DK017047, R01 DK083471] NR 34 TC 14 Z9 15 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD SEP PY 2013 VL 15 SU 3 SI SI BP 137 EP 140 DI 10.1111/dom.12167 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 211DV UT WOS:000323885900016 PM 24003930 ER PT J AU Mckay, RR Choueiri, TK Taplin, ME AF McKay, Rana R. Choueiri, Toni K. Taplin, Mary-Ellen TI Rationale for and Review of Neoadjuvant Therapy Prior to Radical Prostatectomy for Patients with High-Risk Prostate Cancer SO DRUGS LA English DT Review ID PHASE-II TRIAL; COMPLETE ANDROGEN BLOCKADE; TERM-FOLLOW-UP; HORMONAL-THERAPY; CHEMOHORMONAL THERAPY; TUMOR VOLUME; INDEPENDENT PREDICTOR; DISEASE RECURRENCE; RANDOMIZED-TRIAL; BREAST-CANCER AB Despite state of the art local therapy, a significant portion of men with high-risk prostate cancer develop progressive disease. Neoadjuvant systemic therapy prior to radical prostatectomy (RP) is an approach that can potentially maximize survival outcomes in patients with localized disease. This approach is under investigation with a wide array of agents and provides an opportunity to assess pathologic and biologic activity of novel treatments. The aim of this review is to explore the past and present role of neoadjuvant therapy prior to definitive therapy with RP in patients with high-risk localized or locally advanced disease. The results of neoadjuvant androgen-deprivation therapy (ADT), including use of newer agents such as abiraterone, are promising. Neoadjuvant chemotherapy, primarily with docetaxel, with or without ADT has also demonstrated efficacy in men with high-risk disease. Other novel agents targeting the vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), clusterin, and the immune system are currently under investigation and have led to variable results in early clinical trials. Despite optimistic data, approval of neoadjuvant therapy prior to RP in patients with high-risk prostate cancer will depend on positive results from well designed phase III trials. C1 [McKay, Rana R.; Choueiri, Toni K.; Taplin, Mary-Ellen] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM mary_taplin@dfci.harvard.edu FU Fairweather and Uribe Family Prostate Cancer Research Funds FX Mary-Ellen Taplin received support from the Fairweather and Uribe Family Prostate Cancer Research Funds. NR 98 TC 8 Z9 8 U1 1 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD SEP PY 2013 VL 73 IS 13 BP 1417 EP 1430 DI 10.1007/s40265-013-0107-2 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 216YX UT WOS:000324324200004 PM 23943203 ER PT J AU McMillan, GP Reavis, KM Konrad-Martin, D Dille, MF AF McMillan, Garnett P. Reavis, Kelly M. Konrad-Martin, Dawn Dille, Marilyn F. TI The Statistical Basis for Serial Monitoring in Audiology SO EAR AND HEARING LA English DT Article ID PRODUCT OTOACOUSTIC EMISSIONS; TEST-RETEST RELIABILITY; SAMPLE-SIZE; SOUND-LEVEL; CALIBRATION AB Objectives: Audiologists regularly use serial monitoring to evaluate changes in a patient's auditory function over time. Observed changes are compared with reference standards to determine whether further clinical action is necessary. Reference standards are established in a control sample of otherwise healthy subjects to identify the range of auditory shifts that one might reasonably expect to occur in the absence of any pathological insult. Statistical approaches to this seemingly mundane problem typically invoke 1 of 3 approaches: percentiles of the cumulative distribution, the variance of observed shifts, and the standard error of measurement. In this article, the authors describe the statistical foundation for these approaches, along with a mixed model-based alternative, and identify several necessary, although typically unacknowledged assumptions. Regression to the mean, the phenomenon of an unusual measurement typically followed by a more common one, can seriously bias observed changes in auditory function and clinical expectations. An approach that adjusts for this important effect is also described. Design: Distortion product otoacoustic emissions (DPOAEs) elicited at a single primary frequency, f(2) of 3175 Hz, were collected from 32 healthy subjects at baseline and 19 to 29 days later. Ninety percent test-retest reference limits were computed from these data using each statistical approach. DPOAE shifts were also collected from a sample of 18 cisplatin patients tested after 120 to 200mg of cisplatin. Reference limits established according to each of the statistical approaches in the healthy sample were used to identify clinically alarming DPOAE shifts in the cisplatin patient sample. Results: Reference limits established with any of the parametric methods were similar. The percentile-based approach gave the widest and least precisely estimated intervals. The highest sensitivity for detecting clinically alarming DPOAE shifts was based on a mixed model approach that adjusts for regression to the mean. Conclusions: Parametric methods give similar serial monitoring criteria as long as certain critical assumptions are met by the data. The most flexible method for estimating test-retest limits is based on the linear mixed model. Clinical sensitivity may be further enhanced by adjusting for regression to the mean. C1 [McMillan, Garnett P.; Reavis, Kelly M.; Konrad-Martin, Dawn; Dille, Marilyn F.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Vet Affairs Rehabil Res & Dev Serv VA RR&D, Portland, OR USA. [McMillan, Garnett P.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Konrad-Martin, Dawn; Dille, Marilyn F.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. RP McMillan, GP (reprint author), Portland VA Med Ctr, NCRAR, 3710 US Vet Hosp Rd P5, Portland, OR USA. EM garnett.mcmillan@va.gov OI Reavis, Kelly/0000-0002-4906-1010 FU Department of Veterans Affairs Rehabilitation Research and Development Service [C4183R, C7113N]; VA RR&D National Center for Rehabilitative Auditory Research, Portland, Oregon FX This work was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (grants C4183R and C7113N) and the VA RR&D National Center for Rehabilitative Auditory Research, Portland, Oregon. NR 22 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD SEP PY 2013 VL 34 IS 5 BP 610 EP 618 DI 10.1097/AUD.0b013e31828a21b3 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 213JL UT WOS:000324052800010 PM 23563060 ER PT J AU Gattelli, A Nalvarte, I Boulay, A Roloff, TC Schreiber, M Carragher, N Macleod, KK Schlederer, M Lienhard, S Kenner, L Torres-Arzayus, MI Hynes, NE AF Gattelli, Albana Nalvarte, Ivan Boulay, Anne Roloff, Tim C. Schreiber, Martin Carragher, Neil Macleod, Kenneth K. Schlederer, Michaela Lienhard, Susanne Kenner, Lukas Torres-Arzayus, Maria I. Hynes, Nancy E. TI Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells SO EMBO MOLECULAR MEDICINE LA English DT Article DE endocrine-therapy; Fak; IL6; metastasis; Ret ID REVERSE TRANSCRIPTION-PCR; ENDOCRINE RESISTANCE; GENE-EXPRESSION; TUMOR-FORMATION; FERM DOMAIN; KINASE; MECHANISMS; PATHWAY; FUSIONS; FAK AB We show that elevated levels of Ret receptor are found in different sub-types of human breast cancers and that high Ret correlates with decreased metastasis-free survival. The role of Ret in ER+ breast cancer models was explored combining in vitro and in vivo approaches. Our analyses revealed that ligand-induced Ret activation: (i) stimulates migration of breast cancer cells; (ii) rescues cells from anti-proliferative effects of endocrine treatment and (iii) stimulates expression of cytokines in the presence of endocrine agents. Indeed, we uncovered a positive feed-forward loop between the inflammatory cytokine IL6 and Ret that links them at the expression and the functional level. In vivo inhibition of Ret in a metastatic breast cancer model inhibits tumour outgrowth and metastatic potential. Ret inhibition blocks the feed-forward loop by down-regulating Ret levels, as well as decreasing activity of Fak, an integrator of IL6-Ret signalling. Our results suggest that Ret kinase should be considered as a novel therapeutic target in subsets of breast cancer. C1 [Gattelli, Albana; Nalvarte, Ivan; Boulay, Anne; Roloff, Tim C.; Lienhard, Susanne; Hynes, Nancy E.] Friedrich Miescher Inst Biomed Res FMI, Basel, Switzerland. [Schreiber, Martin] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria. [Schreiber, Martin] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Carragher, Neil; Macleod, Kenneth K.] Univ Edinburgh, Coll Med & Vet Med, Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. [Schlederer, Michaela; Kenner, Lukas] LBI CR, Vienna, Austria. [Kenner, Lukas] Med Univ Vienna, Clin Inst Pathol, Vienna, Austria. [Torres-Arzayus, Maria I.] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. [Torres-Arzayus, Maria I.] Harvard Univ, Sch Med, Boston, MA USA. [Hynes, Nancy E.] Univ Basel, Basel, Switzerland. RP Hynes, NE (reprint author), Friedrich Miescher Inst Biomed Res FMI, Basel, Switzerland. EM nancy.hynes@fmi.ch RI Schreiber, Martin/F-2175-2013; OI Schreiber, Martin/0000-0003-1102-7789; Nalvarte, Ivan/0000-0001-6828-2583; Kenner, Lukas/0000-0003-2184-1338 FU Susan G. Komen for the Cure(R) [KG101234]; Novartis Research Foundation FX We thank Dr. Margaret Frame (University of Edinburgh, Edinburgh, UK), Dr. Myles Brown (Dana Farber Cancer Institute, Boston), Drs. Giorgio Caravatti and Thomas Radimerski (Novartis Institutes for Biomedical Research, Basel) and all members of the Hynes lab for helpful discussions. AG was supported by grant KG101234 from Susan G. Komen for the Cure (R). The Hynes lab was supported by Novartis Research Foundation. NR 36 TC 24 Z9 24 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD SEP PY 2013 VL 5 IS 9 BP 1335 EP 1350 DI 10.1002/emmm.201302625 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 209TN UT WOS:000323783000006 PM 23868506 ER PT J AU Cash, SS AF Cash, Sydney S. TI Status epilepticus as a system disturbance: Is status epilepticus due to synchronization or desynchronization? SO EPILEPSIA LA English DT Article DE Action potential; Hypersynchronization; Scale; Seizure termination; Synaptic input ID FOCAL EPILEPSY; SEIZURES; DYNAMICS; EEG AB The traditional view of seizure activity is one in which there is extreme hypersynchronization. Although what is meant by hypersynchronization is rarely explicitly and fully defined, it can be understood to imply large numbers of neurons firing together essentially simultaneously. In this discussion we explore the possibility that seizuresboth self-terminating and sustained in statusare not purely synchronous in time or in space. We investigate the alternative possibility that much seizure activity represents spatiotemporal desynchronization. Furthermore, we discuss the possibility that, in contrast to canonical views of epileptic activity, a high degree of synchronization is a prerequisite for termination of the seizure rather than a marker of early and ongoing seizure activity. These ideas will be discussed with reference to results from our collaborative group based on microelectrode recordings in patients with epilepsy as well as to the many studies done by others in both patients and animal models. Finally, we will explore implications for these hypotheses in the treatment of patients with epilepsy and in status epilepticus. C1 [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cash, SS (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 730,55 Fruit St, Boston, MA 02114 USA. EM scash@partners.org FU NIH/NINDS; CIMIT; Grass Foundation FX The author wishes to thank Drs. Cole, Truccolo, Ahmed, Kramer, and others who have been instrumental in gathering data for related works and in many discussions about these topics that have helped in the formulation of the theoretical framework explored here. Work on these topics has been supported by the NIH/NINDS, CIMIT, and the Grass Foundation. NR 15 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2013 VL 54 SU 6 SI SI BP 37 EP 39 DI 10.1111/epi.12273 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 210JA UT WOS:000323826600011 PM 24001069 ER PT J AU Wasterlain, CG Naylor, DE Liu, H Niquet, J Baldwin, R AF Wasterlain, Claude G. Naylor, David E. Liu, Hantao Niquet, Jerome Baldwin, Roger TI Trafficking of NMDA receptors during status epilepticus: Therapeutic implications SO EPILEPSIA LA English DT Article DE NMDA receptor; Receptor trafficking; Status epilepticus; Acute seizures; Cholinergic seizures; Epilepsy; Monotherapy; Hippocampus ID SUSTAINING STATUS EPILEPTICUS; EPILEPTOGENESIS; ANTAGONISTS AB We used two models of status epilepticus (SE) to study trafficking of N-methyl-d-aspartate (NMDA) receptors. SE is associated with increased surface expression of NR1 subunits of NMDA receptors, and with an increase of NMDA synaptic and extrasynaptic currents suggesting an increase in number of functional NMDA receptors on dentate granule cells. The therapeutic implications of these results are discussed. C1 [Wasterlain, Claude G.; Naylor, David E.; Liu, Hantao; Niquet, Jerome; Baldwin, Roger] Vet Adm Greater Los Angeles Healthcare Syst, Dept Neurol, West Los Angeles, CA USA. [Wasterlain, Claude G.; Naylor, David E.; Liu, Hantao; Niquet, Jerome] UCLA Brain Res Inst, West Los Angeles, CA USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, West Los Angeles, CA USA. [Naylor, David E.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, West Los Angeles, CA USA. RP Wasterlain, CG (reprint author), West LA VA Med Ctr, Dept Neurol 127, 11301 Wilshire Blvd, West Los Angeles, CA 90073 USA. EM wasterla@ucla.edu FU Research Service of the Veterans Health Administration; NINDS [NS13515, NS074926]; James and Debbie Cho Foundation; VHA (Career Development Award); Los Angeles Biomedical Research Institute FX Supported by the Research Service of the Veterans Health Administration (Merit Review C.W.), by NINDS (NS13515 and NS074926 to C.W.), by the James and Debbie Cho Foundation and by the VHA (Career Development Award to D.N.) and the Los Angeles Biomedical Research Institute (to D.N.). NR 13 TC 17 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2013 VL 54 SU 6 SI SI BP 78 EP 80 DI 10.1111/epi.12285 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 210JA UT WOS:000323826600023 PM 24001081 ER PT J AU Reddy, K Reife, R Cole, AJ AF Reddy, Kiran Reife, Ross Cole, Andrew J. TI SGE-102: A novel therapy for refractory status epilepticus SO EPILEPSIA LA English DT Article DE Clinical trial; Neurosteroid; Anticonvulsant; Randomized; Phase II ID INTENSIVE-CARE-UNIT; PREDICTORS; PROGNOSIS; SEIZURES; MICE AB Refractory status epilepticus (SE) has a mortality rate of up to 35%. Current treatment protocols for the treatment of SE begin with benzodiazepines and then proceed to conventional anticonvulsants. If seizures continue, SE is considered refractory (RSE) and treatment with anesthetic agents in undertaken. Twenty-four h to 48h after initiation of anesthesia with midazolam, pentobarbital or thiopental, or propofol, an attempt is made to wean the anesthetic. If this fails and seizures recur, SE is considered highly refractory (HRSE) and repeated attempts are undertaken. No randomized trial data are available to guide the choice of anesthetic agent in either RSE or HRSE status. Medication resistance in established SE is thought to result, in part, from internalization of synaptic -aminobutyric acid (GABA) receptors, making them unavailable for modulation. Neurosteroids act on both synaptic and extrasynaptic GABA(A) receptors, which are not internalized, and are therefore hypothesized to have a role in the treatment of RSE. SGE-102 is a neurosteroid metabolite of progesterone with demonstrated anticonvulsant properties in animal seizure models. A randomized double-blind placebo-controlled adjunctive trial of SGE will include subjects randomized at the time that initial treatment with anesthesia is initiated. Subjects will receive midazolam and either SGE-102 or placebo. Midazolam will be tapered and discontinued between hours 24 and 48. SGE-102 or placebo will be continued through hour 120. The primary end point will be the difference in proportion of subjects from each arm who remain seizure free through hour 120. Secondary end points will include the proportion of subjects who are seizure free at hour 168, 2days after discontinuation of the experimental agent. The study will be powered to have a 90% chance of detecting a clinically meaningful reduction in seizure recurrence at 120h. Comprehensive safety and pharmacokinetic data will also be obtained during the course of the trial. C1 [Reddy, Kiran; Reife, Ross] SAGE Therapeut, Cambridge, MA USA. [Cole, Andrew J.] Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA USA. [Cole, Andrew J.] Harvard Univ, Sch Med, Boston, MA 02214 USA. RP Cole, AJ (reprint author), Harvard Univ, Sch Med, MGH Epilepsy Serv, Massachusetts Gen Hosp, Wang ACC 739 L,Fruit St, Boston, MA 02214 USA. EM cole.andrew@mgh.harvard.edu FU Suovion; Neuropace FX Dr. Reddy is an employee of Sage Therapeutics and Third Rock Ventures. Dr. Reife is an employee of Sage Therapeutics. Dr. Cole is a consultant to Sage Therapeutics. He has served as a consultant to Eisai Pharmaceuticals, Impax Pharmaceuticals, Upsher-Smith Pharmaceuticals, and Neuropace, Inc. He has received funding for conducting clinical trials sponsored by Suovion and Neuropace. NR 17 TC 6 Z9 6 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2013 VL 54 SU 6 SI SI BP 81 EP 83 DI 10.1111/epi.12286 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 210JA UT WOS:000323826600024 PM 24001082 ER PT J AU Vaitkevicius, H Ng, M Moura, L Rosenthal, E Westover, MB Rosand, J Rogawski, MA Reddy, K Cole, AJ AF Vaitkevicius, H. Ng, M. Moura, L. Rosenthal, E. Westover, M. B. Rosand, J. Rogawski, M. A. Reddy, K. Cole, A. J. TI SUCCESSFUL ALLOPREGNANOLONE TREATMENT OF NEW ONSET REFRACTORY STATUS EPILEPTICUS (NORSE) SYNDROME: FIRST IN MAN EXPERIENCE SO EPILEPSIA LA English DT Meeting Abstract CT 4th London-Innsbruck-Colloquium on Status Epilepticus CY APR 04-06, 2013 CL Salzburg, AUSTRIA C1 [Vaitkevicius, H.; Rosenthal, E.; Rosand, J.] Massachusetts Gen Hosp, MGH Neurosci Intens Care Unit, Boston, MA 02114 USA. [Ng, M.; Moura, L.; Westover, M. B.; Cole, A. J.] Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. [Rogawski, M. A.] UC Davis Med Sch, Dept Neurol, Sacramento, CA USA. [Reddy, K.] Sage Therapeut, Cambridge, MA USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2013 VL 54 SU 6 SI SI BP 114 EP 114 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 210JA UT WOS:000323826600059 ER PT J AU Wielputz, MO Lederlin, M Wroblewski, J Dinkel, J Eichinger, M Biederer, J Kauczor, HU Puderbach, M AF Wielpuetz, Mark O. Lederlin, Mathieu Wroblewski, Jacek Dinkel, Julien Eichinger, Monika Biederer, Juergen Kauczor, Hans-Ulrich Puderbach, Michael TI CT volumetry of artificial pulmonary nodules using an ex vivo lung phantom: Influence of exposure parameters and iterative reconstruction on reproducibility SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Lung cancer; Screening; Computer-aided diagnosis ID LOW-DOSE CT; IMAGE QUALITY; CHEST CT; COMPUTED-TOMOGRAPHY; SCREENING TRIAL; HELICAL CT; CANCER; MANAGEMENT; GUIDELINES; STATEMENT AB Objectives: To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the measurement variability of computer-aided nodule volumetry on chest multidetector computed tomography (MDCT). Materials and methods: N=7 porcine lung explants were inflated in a dedicated ex vivo phantom and prepared with n=162 artificial nodules. MDCT was performed eight consecutive times (combinations of 120 and 80 kV with 120, 60,30 and 12 mA s), and reconstructed with filtered back projection (FBP) and IR. Nodule volume and diameter were measured semi-automatically with dedicated software. The absolute percentage measurement error (APE) was computed in relation to the 120 kV 120 mA s acquisition. Noise was recorded for each nodule in every dataset. Results: Mean nodule volume and diameter were 0.32 +/- 0.15 ml and 12.0 +/- 2.6 mm, respectively. Although IR reduced noise by 24.9% on average compared to FBP (p<0.007), APE with IR was equal to or slightly higher than with FBP. Mean APE for volume increased significantly below a volume computed tomography dose index (CTDI) of 1.0 mGy: for 120 kV 12 mA s APE was 3.8 +/- 6.2% (FBP) vs. 4.0 +/- 5.2% (IR) (p<0.007); for 80 kV 12 mA s APE was 8.0 +/- 13.0% vs. 9.3 +/- 15.8% (n.s.), respectively. Correlating APE with image noise revealed that at identical noise APE was higher with IR than with FBP (p<0.05). Conclusions: Computer-aided volumetry is robust in a wide range of exposure settings, and reproducibility is reduced at a CTDI below 1.0 mGy only, but the error rate remains clinically irrelevant. Noise reduction by IR is not detrimental for measurement error in the setting of semi-automatic nodule volumetry on chest MDCT. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Wielpuetz, Mark O.; Wroblewski, Jacek; Biederer, Juergen; Kauczor, Hans-Ulrich] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, D-69120 Heidelberg, Germany. [Wielpuetz, Mark O.; Wroblewski, Jacek; Dinkel, Julien; Eichinger, Monika; Biederer, Juergen; Kauczor, Hans-Ulrich; Puderbach, Michael] German Ctr Lung Res DZL, Translat Lung Res Ctr TLRC H, D-69120 Heidelberg, Germany. [Lederlin, Mathieu] Univ Hosp Bordeaux, Dept Thorac & Cardiovasc Imaging, F-33600 Pessac, France. [Lederlin, Mathieu; Dinkel, Julien; Eichinger, Monika; Puderbach, Michael] German Canc Res Ctr, Dept Radiol, D-69120 Heidelberg, Germany. [Dinkel, Julien] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Eichinger, Monika; Puderbach, Michael] Heidelberg Univ, Thoraxklin, Dept Diagnost & Intervent Radiol Nucl Med, D-69126 Heidelberg, Germany. RP Wielputz, MO (reprint author), Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Neuenheimer Feld 110, D-69120 Heidelberg, Germany. EM Mark.wielpuetz@med.uni-heidelberg.de; mathieu.lederlin@chu-bordeaux.fr; JacekWr@gmx.net; jdinkel@partners.org; Monika.eichinger@thoraxklinik-heidelberg.de; Juergen.biederer@uni-heidelberg.de; hu.kauczor@med.uni-heidelberg.de; Michael.puderbach@thoraxklinik-heidelberg.de RI Biederer, Juergen/E-4545-2010; OI Wielputz, Mark Oliver/0000-0001-6962-037X FU German Center for Lung Research (DZL) from the Bundesministerium fur Bildung und Forschung (BMBF) of the federal government of Germany [82DZL00401, 82DZL00402, 82DZL00404] FX This study was supported by the German Center for Lung Research (DZL) through grants from the Bundesministerium fur Bildung und Forschung (BMBF) of the federal government of Germany (82DZL00401, 82DZL00402, 82DZL00404). NR 30 TC 9 Z9 10 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD SEP PY 2013 VL 82 IS 9 BP 1577 EP 1583 DI 10.1016/j.ejrad.2013.04.035 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 211TZ UT WOS:000323935200049 PM 23727376 ER PT J AU Sadrzadeh, H Kerr, DA Dal Cin, P Lindeman, NI Hasserjian, RP Ballen, KK Fathi, AT AF Sadrzadeh, Hossein Kerr, Darcy A. Dal Cin, Paola Lindeman, Neal I. Hasserjian, Robert P. Ballen, Karen K. Fathi, Amir T. TI A unique PML-RAR alpha rearrangement involving chromosomes 11, 15, and 17 in a patient with acute promyelocytic leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Letter ID GENE; TRANSLOCATIONS; T(15/17); APL C1 [Sadrzadeh, Hossein; Ballen, Karen K.; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA 02114 USA. [Kerr, Darcy A.; Hasserjian, Robert P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Dal Cin, Paola; Lindeman, Neal I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Fathi, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA 02114 USA. EM afathi@partners.org NR 10 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2013 VL 41 IS 9 BP 769 EP 771 DI 10.1016/j.exphem.2013.04.011 PG 3 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 217KU UT WOS:000324359200002 PM 23660071 ER PT J AU Leung, FW AF Leung, Felix W. TI Water-aided Colonoscopy SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Colonoscopy; Water-aided method; Discomfort; Pain; Adenoma detection rate; Water immersion; Water exchange ID UNSEDATED COLONOSCOPY; WARM WATER; SEDATED COLONOSCOPY; AIR INSUFFLATION; PATIENT TOLERANCE; CECAL INTUBATION; MINIMAL SEDATION; CONTROLLED-TRIAL; US VETERANS; INFUSION AB Water-aided methods for colonoscopy include the established water immersion and the recent novel modification of water exchange. Water immersion entails the use of water as an adjunct to air insufflations to facilitate insertion. Water exchange evolved from water immersion to facilitate completion of colonoscopy without discomfort in unsedated patients. Infused water is removed predominantly during insertion rather than withdrawal. A higher adenoma detection rate has been reported with water exchange. Aggregate data of randomized controlled trials suggest that water exchange may be superior to water immersion in attenuating colonoscopy discomfort and optimizing adenoma detection, particularly in the proximal colon. C1 [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Dept Med, Div Gastroenterol, North Hills, CA 91343 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Dept Med, Div Gastroenterol, 111G,16111 Plummer St, North Hills, CA 91343 USA. EM felix.leung@va.gov FU Veterans Affairs Medical Research Funds at Veterans Affairs Greater Los Angeles Healthcare System; American College of Gastroenterology Clinical Research Award FX The study is supported in part by Veterans Affairs Medical Research Funds at Veterans Affairs Greater Los Angeles Healthcare System and an American College of Gastroenterology Clinical Research Award (FWL). NR 50 TC 5 Z9 5 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2013 VL 42 IS 3 BP 507 EP + DI 10.1016/j.gtc.2013.05.006 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 215PA UT WOS:000324221500007 PM 23931857 ER PT J AU Brugge, WR AF Brugge, William R. TI EUS SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID FINE-NEEDLE-ASPIRATION; DIAGNOSTIC YIELD; GALLBLADDER DRAINAGE; FLUID COLLECTIONS; PANCREATIC CYSTS; CONTROLLED-TRIAL; GUIDED DRAINAGE; METAL STENT; FNA; VIDEOS C1 Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA 02214 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, Blake 4,55 Fruit St, Boston, MA 02214 USA. FU RedPath integrated Pathology FX Dr Brugge received a research grant from RedPath integrated Pathology. NR 38 TC 2 Z9 2 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2013 VL 78 IS 3 BP 414 EP 420 DI 10.1016/j.gie.2013.07.002 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 212XV UT WOS:000324017000004 PM 23948189 ER PT J AU Jayadev, S Bird, TD AF Jayadev, Suman Bird, Thomas D. TI Hereditary ataxias: overview SO GENETICS IN MEDICINE LA English DT Review DE ataxia; cerebellum; neurogenetics ID ONSET SPINOCEREBELLAR ATAXIA; RECESSIVE CEREBELLAR-ATAXIA; GENETICALLY DEFINED SUBTYPES; MARINESCO-SJOGREN-SYNDROME; OCULAR MOTOR APRAXIA; ADULT-ONSET; COENZYME-Q10 DEFICIENCY; POLYGLUTAMINE EXPANSIONS; TREMOR/ATAXIA SYNDROME; MOLECULAR DIAGNOSIS AB The hereditary ataxias are a highly heterogeneous group of disorders phenotypically characterized by gait ataxia, incoordination of eye movements, speech, and hand movements, and usually associated with atrophy of the cerebellum. There are more than 35 autosomal dominant types frequently termed spinocerebellar ataxia and typically having adult onset. The most common subtypes are spinocerebellar ataxia 1, 2, 3, 6, and 7, all of which are nucleotide repeat expansion disorders. Autosomal recessive ataxias usually have onset in childhood; the most common subtypes are Friedreich, ataxia-telangiectasia, ataxia with oculomotor apraxia type 1, and ataxia with oculomotor apraxia type 2. Four autosomal recessive types have dietary or biochemical treatment modalities (ataxia with vitamin E deficiency, cerebrotendinous xanthomatosis, Refsum, and coenzyme Q10 deficiency), whereas there are no specific treatments for other ataxias. Diagnostic genetic testing is complicated because of the large number of relatively uncommon subtypes with extensive phenotypic overlap. However, the best testing strategy is based on assessing relative frequencies, ethnic predilections, and recognition of associated phenotypic features such as seizures, visual loss, or associated movement abnormalities. C1 [Jayadev, Suman; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas D.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Bird, TD (reprint author), Univ Washington, Dept Neurol, Seattle, WA 98195 USA. EM tomnroz@uw.edu FU Veterans Affairs Research; National Center for Biotechnology Information FX This study was supported by funding from Veterans Affairs Research and the National Center for Biotechnology Information. This overview represents a revised and updated version of Thomas D. Bird's Hereditary Ataxia in GeneReviews at GeneTests: Medical Genetics Information Resource (online resource). Copyright University of Washington, Seattle, Washington, 1998-2012. http://www.genetests.org. NR 80 TC 25 Z9 26 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP PY 2013 VL 15 IS 9 BP 673 EP 683 DI 10.1038/gim.2013.28 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 214XN UT WOS:000324172000002 PM 23538602 ER PT J AU Rehm, HL Bale, SJ Bayrak-Toydemir, P Berg, JS Brown, KK Deignan, JL Friez, MJ Funke, BH Hegde, MR Lyon, E AF Rehm, Heidi L. Bale, Sherri J. Bayrak-Toydemir, Pinar Berg, Jonathan S. Brown, Kerry K. Deignan, Joshua L. Friez, Michael J. Funke, Birgit H. Hegde, Madhuri R. Lyon, Elaine CA Amer Coll Med Genetics Genomics Lab Quality Assurance TI ACMG clinical laboratory standards for next-generation sequencing SO GENETICS IN MEDICINE LA English DT Article DE ACMG; exome sequencing; genome sequencing; guidelines; next-generation sequencing; standards ID EXOME; RECOMMENDATIONS; FRAMEWORK; GENOME; TESTS AB Next-generation sequencing technologies have been and continue to be deployed in clinical laboratories, enabling rapid transformations in genomic medicine. These technologies have reduced the cost of large-scale sequencing by several orders of magnitude, and continuous advances are being made. It is now feasible to analyze an individual's near-complete exome or genome to assist in the diagnosis of a wide array of clinical scenarios. Next-generation sequencing technologies are also facilitating further advances in therapeutic decision making and disease prediction for at-risk patients. However, with rapid advances come additional challenges involving the clinical validation and use of these constantly evolving technologies and platforms in clinical laboratories. To assist clinical laboratories with the validation of next-generation sequencing methods and platforms, the ongoing monitoring of next-generation sequencing testing to ensure quality results, and the interpretation and reporting of variants found using these technologies, the American College of Medical Genetics and Genomics has developed the following professional standards and guidelines. C1 [Rehm, Heidi L.; Funke, Birgit H.] Partners Healthcare Ctr Personalized Genet Med, Lab Mol Med, Boston, MA USA. [Rehm, Heidi L.; Funke, Birgit H.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. [Rehm, Heidi L.; Funke, Birgit H.] Harvard Univ, Sch Med, Boston, MA USA. [Bale, Sherri J.] GeneDx, Gaithersburg, MD USA. [Bayrak-Toydemir, Pinar; Lyon, Elaine] Univ Utah, Dept Pathol, ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA. [Berg, Jonathan S.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Brown, Kerry K.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Deignan, Joshua L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Friez, Michael J.] Greenwood Genet Ctr, Mol Diagnost Lab, Greenwood, SC 29646 USA. [Hegde, Madhuri R.] Emory Univ, Dept Human Genet, Emory Genet Lab, Atlanta, GA 30322 USA. RP Rehm, HL (reprint author), Partners Healthcare Ctr Personalized Genet Med, Lab Mol Med, Boston, MA USA. EM hrehm@partners.org FU National Institutes of Health [HG006500] FX Members of the ACMG Working Group on Next-Generation Sequencing were all reviewed for conflicts of interest by the Board of the ACMG. This document was approved by the ACMG Board of Directors, 22 April 2013. H. L. R. was supported in part by National Institutes of Health grant HG006500. NR 19 TC 227 Z9 233 U1 7 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP PY 2013 VL 15 IS 9 BP 733 EP 747 DI 10.1038/gim.2013.92 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 214XN UT WOS:000324172000010 PM 23887774 ER PT J AU Jia, PL Jin, HL Meador, CB Xia, JF Ohashi, K Liu, L Pirazzoli, V Dahlman, KB Politi, K Michor, F Zhao, ZM Pao, W AF Jia, Peilin Jin, Hailing Meador, Catherine B. Xia, Junfeng Ohashi, Kadoaki Liu, Lin Pirazzoli, Valentina Dahlman, Kimberly B. Politi, Katerina Michor, Franziska Zhao, Zhongming Pao, William TI Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance SO GENOME RESEARCH LA English DT Article ID COPY-NUMBER ALTERATIONS; ACQUIRED-RESISTANCE; HUMAN GENOME; T790M MUTATIONS; RNA-SEQ; GEFITINIB; AMPLIFICATION; RESOLUTION; DOMAIN; MET AB Somatic mutations in kinase genes are associated with sensitivity of solid tumors to kinase inhibitors, but patients with metastatic cancer eventually develop disease progression. In EGFR mutant lung cancer, modeling of acquired resistance (AR) with drug-sensitive cell lines has identified clinically relevant EGFR tyrosine kinase inhibitor (TKI) resistance mechanisms such as the second-site mutation, EGFR T790M, amplification of the gene encoding an alternative kinase, MET, and epithelial mesenchymal transition (EMT). The full spectrum of DNA changes associated with AR remains unknown. We used next-generation sequencing to characterize mutational changes associated with four populations of EGFR mutant drug-sensitive and five matched drug-resistant cell lines. Comparing resistant cells with parental counterparts, 18-91 coding SNVs/Indels were predicted to be acquired and 1-27 were lost; few SNVs/indels were shared across resistant lines. Comparison of two related parental lines revealed no unique coding SNVs/indels, suggesting that changes in the resistant lines were due to drug selection. Surprisingly, we observed more CNV changes across all resistant lines, and the line with EMT displayed significantly higher levels of CNV changes than the other lines with AR. These results demonstrate a framework for studying the evolution of AR and provide the first genome-wide spectrum of mutations associated with the development of cellular drug resistance in an oncogene-addicted cancer. Collectively, the data suggest that CNV changes may play a larger role than previously appreciated in the acquisition of drug resistance and highlight that resistance may be heterogeneous in the context of different tumor cell backgrounds. C1 [Jia, Peilin; Xia, Junfeng; Zhao, Zhongming] Vanderbilt Univ, Dept Biomed Informat, Sch Med, Nashville, TN 37232 USA. [Jin, Hailing; Meador, Catherine B.; Ohashi, Kadoaki; Pao, William] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. [Liu, Lin; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Liu, Lin; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Pirazzoli, Valentina; Politi, Katerina] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Pirazzoli, Valentina; Politi, Katerina] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06510 USA. [Dahlman, Kimberly B.; Zhao, Zhongming; Pao, William] Vanderbilt Univ, Dept Canc Biol, Sch Med, Nashville, TN 37232 USA. [Politi, Katerina] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. RP Zhao, ZM (reprint author), Vanderbilt Univ, Dept Biomed Informat, Sch Med, Nashville, TN 37232 USA. EM zhongming.zhao@vanderbilt.edu; william.pao@vanderbilt.edu FU National Institutes of Health (NIH) NCI [R01CA121210, P01CA129243, U54CA143798]; American Association for Cancer Research [SU2C-AACR-IRG0109]; Vanderbilt's Specialized Program of Research Excellence in Lung Cancer grant [P50CA90949]; VICC Cancer Center Core grant [P30CA68485]; NIH/NCI [R01CA120247, R00CA131488]; Labrecque Foundation; Uniting Against Lung Cancer; NIH [U54CA143798, P30CA68485, R01LM011177]; Ingram Professorship Funds FX This work was supported by funds from the National Institutes of Health (NIH) NCI grants R01CA121210, P01CA129243, and U54CA143798 and American Association for Cancer Research, Stand Up to Cancer Innovative Research Grant (SU2C) SU2C-AACR-IRG0109. W.P. received additional support from Vanderbilt's Specialized Program of Research Excellence in Lung Cancer grant (P50CA90949) and from the VICC Cancer Center Core grant (P30CA68485). P.J. and Z.Z. received support from SU2C-AACR-IRG0109. K.P. received support from NIH/NCI grants R01CA120247 and R00CA131488, the Labrecque Foundation, and Uniting Against Lung Cancer. Z.Z. received additional support from NIH grants R01LM011177 and P30CA68485 and Ingram Professorship Funds. L.L., F.M., and W.P. received support from NIH grant U54CA143798. NR 47 TC 20 Z9 20 U1 0 U2 20 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2013 VL 23 IS 9 BP 1434 EP 1445 DI 10.1101/gr.152322.112 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 213SJ UT WOS:000324080000007 PM 23733853 ER PT J AU Zhang, B Zhou, Y Lin, N Lowdon, RF Hong, CB Nagarajan, RP Cheng, JB Li, DF Stevens, M Lee, HJ Xing, XY Zhou, J Sundaram, V Elliott, G Gu, JC Shi, TP Gascard, P Sigaroudinia, M Tisty, TD Kadlecek, T Weiss, A O'Geen, H Farnham, PJ Maire, CL Ligon, KL Madden, PAF Tam, A Moore, R Hirst, M Marra, MA Zhang, B Costello, JF Wang, T AF Zhang, Bo Zhou, Yan Lin, Nan Lowdon, Rebecca F. Hong, Chibo Nagarajan, Raman P. Cheng, Jeffrey B. Li, Daofeng Stevens, Michael Lee, Hyung Joo Xing, Xiaoyun Zhou, Jia Sundaram, Vasavi Elliott, GiNell Gu, Junchen Shi, Taoping Gascard, Philippe Sigaroudinia, Mahvash Tisty, Thea D. Kadlecek, Theresa Weiss, Arthur O'Geen, Henriette Farnham, Peggy J. Maire, Cecile L. Ligon, Keith L. Madden, Pamela A. F. Tam, Angela Moore, Richard Hirst, Martin Marra, Marco A. Zhang, Baoxue Costello, Joseph F. Wang, Ting TI Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm SO GENOME RESEARCH LA English DT Article ID EPIGENETIC TRANSGENERATIONAL INHERITANCE; CD4(+) T-CELLS; BREAST-CANCER; HUMAN GENOME; CYTOSINE METHYLATION; REGULATORY REGIONS; EPIGENOME BROWSER; BASE-RESOLUTION; GENE-CLUSTER; SEQ DATA AB DNA methylation plays key roles in diverse biological processes such as X chromosome inactivation, transposable element repression, genomic imprinting, and tissue-specific gene expression. Sequencing-based DNA methylation profiling provides an unprecedented opportunity to map and compare complete DNA methylomes. This includes one of the most widely applied technologies for measuring DNA methylation: methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq), coupled with a complementary method, methylation-sensitive restriction enzyme sequencing (MRE-seq). A computational approach that integrates data from these two different but complementary assays and predicts methylation differences between samples has been unavailable. Here, we present a novel integrative statistical framework MUM (for integration of MeDIP-seq and MRE-seq) that dynamically scales, normalizes, and combines MeDIP-seq and MRE-seq data to detect differentially methylated regions. Using sample-matched whole-genome bisulfite sequencing (WGBS) as a gold standard, we demonstrate superior accuracy and reproducibility of MUM compared to existing analytical methods for MeDIP-seq data alone. M&M leverages the complementary nature of MeDIP-seq and MRE-seq data to allow rapid comparative analysis between whole methylomes at a fraction of the cost of WGBS. Comprehensive analysis of nineteen human DNA methylomes with M&M reveals distinct DNA methylation patterns among different tissue types, cell types, and individuals, potentially underscoring divergent epigenetic regulation at different scales of phenotypic diversity. We find that differential DNA methylation at enhancer elements, with concurrent changes in histone modifications and transcription factor binding, is common at the cell, tissue, and individual levels, whereas promoter methylation is more prominent in reinforcing fundamental tissue identities. C1 [Zhang, Bo; Lowdon, Rebecca F.; Li, Daofeng; Stevens, Michael; Lee, Hyung Joo; Xing, Xiaoyun; Zhou, Jia; Sundaram, Vasavi; Elliott, GiNell; Gu, Junchen; Shi, Taoping; Wang, Ting] Washington Univ, Sch Med, Dept Genet, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA. [Zhou, Yan; Zhang, Baoxue] NE Normal Univ, Key Lab Appl Stat MOE, Changchun 130024, Jilin Province, Peoples R China. [Zhou, Yan; Zhang, Baoxue] NE Normal Univ, Sch Math & Stat, Changchun 130024, Jilin Province, Peoples R China. [Zhou, Yan] Harbin Univ Sci & Technol, Sch Appl Sci, Harbin 150080, Peoples R China. [Lin, Nan] Washington Univ, Dept Math, St Louis, MO 63130 USA. [Lin, Nan] Washington Univ, Div Biostat, St Louis, MO 63130 USA. [Hong, Chibo; Nagarajan, Raman P.; Costello, Joseph F.] Univ Calif San Francisco, Dept Neurosurg, Brain Tumor Res Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Cheng, Jeffrey B.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Gascard, Philippe; Sigaroudinia, Mahvash; Tisty, Thea D.] Univ Calif San Francisco, Dept Pathol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Kadlecek, Theresa; Weiss, Arthur] Univ Calif San Francisco, Howard Hughes Med Inst, Div Rheumatol, San Francisco, CA 94143 USA. [O'Geen, Henriette] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Farnham, Peggy J.] Univ So Calif, Dept Biochem & Mol Biol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Maire, Cecile L.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA. [Ligon, Keith L.] Childrens Hosp, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Madden, Pamela A. F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Tam, Angela; Moore, Richard; Hirst, Martin; Marra, Marco A.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC VSZ 4S6, Canada. [Hirst, Martin] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada. RP Wang, T (reprint author), Washington Univ, Sch Med, Dept Genet, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA. EM bxzhang@nenu.edu.cn; jcostello@cc.ucsf.edu; twang@genetics.wustl.edu RI Zhang, Bao/B-3926-2012; Tang, Macy/B-9798-2014; Zhang, Bo/A-6874-2011; Li, Daofeng/E-5386-2011; Hirst, Martin/B-7684-2016; Marra, Marco/B-5987-2008; OI Gu, Junchen/0000-0002-0928-7453; Zhang, Bo/0000-0003-2962-5314; Li, Daofeng/0000-0001-7492-3703; Kadlecek, Theresa/0000-0002-1020-8169; Farnham, Peggy/0000-0003-4469-7914; Lee, Hyung Joo/0000-0002-7030-5390 FU NIH Roadmap Epigenomics Program; National Institute on Drug Abuse (NIDA); National Institute of Environmental Health Sciences (NIEHS); NIH [5U01ES017154, P01CA095616, P01CA142536]; Basil O'Connor Starter Scholar Research Award from the March of Dimes Foundation [5-FY10-491]; Edward Jr. Mallinckrodt Foundation [P50CA134254, R01HG007354]; Foundation for Barnes-Jewish Hospital; Dermatology Foundation; NIDA's R25 program [DA027995]; Sontag Foundation; Program for the National Science Foundation of China [11271064]; New Century Excellent Talents in University [NCET-09-0248]; Program for Changjiang Scholars and Innovative Research Team in University; Fund of Jilin Provincial Science & Technology Department [20111804]; [NSF-DMS0906023] FX We thank collaborators in the Reference Epigenome Mapping Centers (REMC), Epigenome Data Analysis and Coordination Center, and NCBI who have generated and processed data used in this project. We acknowledge support from the NIH Roadmap Epigenomics Program, sponsored by the National Institute on Drug Abuse (NIDA) and the National Institute of Environmental Health Sciences (NIEHS). J.F.C., M.H., and T.W. are supported by NIH grant 5U01ES017154. T.W. is supported in part by Basil O'Connor Starter Scholar Research Award Grant no. 5-FY10-491 from the March of Dimes Foundation, the Edward Jr. Mallinckrodt Foundation, P50CA134254, R01HG007354, and a grant from the Foundation for Barnes-Jewish Hospital. J.B.C. is supported by a Career Development Award from the Dermatology Foundation. B.Z. is supported by NIDA's R25 program DA027995. K.L.L. and C.L.M. are supported by NIH Grants P01CA095616 and P01CA142536 and a grant from the Sontag Foundation. N.L. is supported by NSF-DMS0906023. Y.Z. and Bx.Z. are supported by the Program for the National Science Foundation of China (no. 11271064), New Century Excellent Talents in University (NCET-09-0248), the Program for Changjiang Scholars and Innovative Research Team in University, and the Fund of Jilin Provincial Science & Technology Department (no. 20111804). NR 101 TC 51 Z9 51 U1 3 U2 46 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD SEP PY 2013 VL 23 IS 9 BP 1522 EP 1540 DI 10.1101/gr.156539.113 PG 19 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 213SJ UT WOS:000324080000015 PM 23804400 ER PT J AU Stevens, M Cheng, JB Li, DF Xie, MC Hong, CB Maire, CL Ligon, KL Hirst, M Marra, MA Costello, JF Wang, T AF Stevens, Michael Cheng, Jeffrey B. Li, Daofeng Xie, Mingchao Hong, Chibo Maire, Cecile L. Ligon, Keith L. Hirst, Martin Marra, Marco A. Costello, Joseph F. Wang, Ting TI Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods SO GENOME RESEARCH LA English DT Article ID WIDE DNA METHYLATION; METHYLOME ANALYSIS; HUMAN GENOME; CELLS; DIFFERENTIATION; EPIGENOMICS; PREDICTION; SITES; MEDIP AB Recent advancements in sequencing-based DNA methylation profiling methods provide an unprecedented opportunity to map complete DNA methylomes. These include whole-genome bisulfite sequencing (WGBS, MethyiC-seq, or BS-seq), reduced-representation bisulfite sequencing (RRBS), and enrichment-based methods such as MeDIP-seq, MBD-seq, and MRE-seq. These methods yield largely comparable results but differ significantly in extent of genomic CpG coverage, resolution, quantitative accuracy, and cost, at least while using current algorithms to interrogate the data. None of these existing methods provides single-CpG resolution, comprehensive genome-wide coverage, and cost feasibility for a typical laboratory. We introduce methylCRF, a novel conditional random fields based algorithm that integrates methylated DNA immunoprecipitation (MeDIP-seq) and methylation-sensitive restriction enzyme (MRE-seq) sequencing data to predict DNA methylation levels at single-CpG resolution. Our method is a combined computational and experimental strategy to produce DNA methylomes of all 28 million CpGs in the human genome for a fraction (<10%) of the cost of whole-genome bisulfite sequencing methods. methylCRF was benchmarked for accuracy against Infinium arrays, RRBS, WGBS sequencing, and locus-specific bisulfite sequencing performed on the same human embryonic stem cell line. methylCRF transformation of MeDIP-seq/MRE-seq was equivalent to a biological replicate of WGBS in quantification, coverage, and resolution. We used conventional bisulfite conversion, PCR, cloning, and sequencing to validate loci where our predictions do not agree with whole-genome bisulfite data, and in 11 out of 12 cases, methylCRF predictions of methylation level agree better with validated results than does whole-genome bisulfite sequencing. Therefore, methylCRF transformation of MeDIP-seq/MRE-seq data provides an accurate, inexpensive, and widely accessible strategy to create full DNA methylomes. C1 [Stevens, Michael; Li, Daofeng; Xie, Mingchao; Wang, Ting] Washington Univ, Sch Med, Dept Genet, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA. [Stevens, Michael; Wang, Ting] Washington Univ, Dept Comp Sci & Engn, St Louis, MO 63130 USA. [Cheng, Jeffrey B.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Hong, Chibo; Costello, Joseph F.] Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Neurosurg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Maire, Cecile L.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hirst, Martin; Marra, Marco A.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr Vancouver, Vancouver, BC V5Z 4S6, Canada. [Hirst, Martin] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada. RP Costello, JF (reprint author), Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Neurosurg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM jcostello@cc.ucsf.edu; twang@genetics.wustl.edu RI Li, Daofeng/E-5386-2011; Hirst, Martin/B-7684-2016; Tang, Macy/B-9798-2014; Marra, Marco/B-5987-2008 OI Li, Daofeng/0000-0001-7492-3703; FU NIH Roadmap Epigenomics Program; National Institute on Drug Abuse (NIDA); National Institute of Environmental Health Sciences (NIEHS); Dermatology Foundation; NIH [5U01ES017154, P01CA095616, P01CA142536]; March of Dimes Foundation [5-FY10-491]; Edward Jr. Mallinckrodt Foundation [P50CA134254, R01HG007354]; Sontag Foundation FX We thank collaborators in the Reference Epigenome Mapping Centers (REMC), Epigenome Data Analysis and Coordination Center, and NCBI who have generated and processed the data used in this project. We acknowledge support from the NIH Roadmap Epigenomics Program, sponsored by the National Institute on Drug Abuse (NIDA) and the National Institute of Environmental Health Sciences (NIEHS). J.B.C. is supported by a Career Development Award from the Dermatology Foundation. J.F.C., M.H., and T.W. are supported by NIH grant 5U01ES017154. T.W. is supported by the Basil O'Connor Starter Scholar Research Award Grant no. 5-FY10-491 from the March of Dimes Foundation, the Edward Jr. Mallinckrodt Foundation, P50CA134254, R01HG007354, and a generous startup package from the Department of Genetics, Washington University. K.L.L. and C.L.M. are supported by NIH Grants P01CA095616 and P01CA142536 and a grant from the Sontag Foundation. T.W. thanks David Haussler for insightful discussions during the early development of the project. NR 43 TC 41 Z9 41 U1 1 U2 34 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD SEP PY 2013 VL 23 IS 9 BP 1541 EP 1553 DI 10.1101/gr.152231.112 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 213SJ UT WOS:000324080000016 PM 23804401 ER PT J AU Greene, DI Spencer, AE Pridgen, BC Cather, C Ablon, S AF Greene, Daniel I. Spencer, Andrea E. Pridgen, Bryan C. Cather, Corinne Ablon, Steven TI Evolving Illness, Shifting Perspectives: Childhood Psychosis Through the Lenses of Family Therapy and Individual Therapy SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE childhood psychosis; cognitive-behavior therapy; family therapy; individual psychotherapy; inpatient hospitalization ID SCHIZOPHRENIA; INTERVENTIONS; DISORDER; CHILDREN; WORK C1 [Greene, Daniel I.; Spencer, Andrea E.; Cather, Corinne; Ablon, Steven] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Greene, Daniel I.; Spencer, Andrea E.; Cather, Corinne; Ablon, Steven] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pridgen, Bryan C.] McLean Hosp, Belmont, MA 02178 USA. RP Greene, DI (reprint author), Cambridge Hosp, 1493 Cambridge St, Cambridge, MA 02139 USA. EM dgreene@challiance.org NR 25 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2013 VL 21 IS 5 BP 259 EP 268 DI 10.1097/HRP.0b013e3182a75c7a PG 10 WC Psychiatry SC Psychiatry GA 219HK UT WOS:000324496700003 PM 24651558 ER PT J AU Desseilles, M Witte, J Chang, TE Iovieno, N Dording, C Ashih, H Nyer, M Freeman, MP Fava, M Mischoulon, D AF Desseilles, Martin Witte, Janet Chang, Trina E. Iovieno, Nadia Dording, Christina Ashih, Heidi Nyer, Maren Freeman, Marlene P. Fava, Maurizio Mischoulon, David TI Massachusetts General Hospital SAFER Criteria for Clinical Trials and Research SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE clinical instrument; clinical trial; depression; diagnosis; recruitment ID ECONOMIC BURDEN; DEPRESSION C1 [Desseilles, Martin] Univ Liege, Cyclotron Res Ctr, B-4000 Liege, Belgium. [Desseilles, Martin; Witte, Janet; Chang, Trina E.; Iovieno, Nadia; Dording, Christina; Ashih, Heidi; Nyer, Maren; Freeman, Marlene P.; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Clin Trials Network & Inst, Boston, MA 02114 USA. [Desseilles, Martin; Witte, Janet; Chang, Trina E.; Iovieno, Nadia; Dording, Christina; Ashih, Heidi; Nyer, Maren; Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Witte, Janet; Chang, Trina E.; Iovieno, Nadia; Dording, Christina; Ashih, Heidi; Nyer, Maren; Freeman, Marlene P.; Fava, Maurizio; Mischoulon, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Desseilles, M (reprint author), Univ Liege, Cyclotron Res Ctr, B30 8 Allee 6 Aout, B-4000 Liege, Belgium. EM m.desseilles@ulg.ac.be NR 9 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2013 VL 21 IS 5 BP 269 EP 274 DI 10.1097/HRP.0b013e3182a75cc7 PG 6 WC Psychiatry SC Psychiatry GA 219HK UT WOS:000324496700004 PM 24651559 ER PT J AU Lertpiriyapong, K Feng, Y Handt, L Mitchell, TW Lodge, K Shen, Z Dewhirst, F Fox, JG AF Lertpiriyapong, K. Feng, Y. Handt, L. Mitchell, T. W. Lodge, K. Shen, Z. Dewhirst, F. Fox, J. G. TI PATHOGENIC PROPERTIES OF ENTEROHEPATIC HELICOBACTER SPP. ASSOCIATED WITH INTESTINAL ADENOCARCINOMA IN RHESUS MACAQUES SO HELICOBACTER LA English DT Meeting Abstract CT 26th International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 12-14, 2013 CL Madrid, SPAIN SP European Helicobacter Study Grp C1 [Lertpiriyapong, K.; Feng, Y.; Shen, Z.; Fox, J. G.] MIT, Cambridge, MA 02139 USA. [Handt, L.; Mitchell, T. W.; Lodge, K.; Dewhirst, F.] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD SEP PY 2013 VL 18 SU 1 SI SI BP 85 EP 85 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 213HT UT WOS:000324047300033 ER PT J AU Swennes, AG Turk, ML Trowel, E Cullin, C Pang, JS Shen, Z Dewhirst, FE Fox, JG AF Swennes, A. G. Turk, M. L. Trowel, E. Cullin, C. Pang, J. S. Shen, Z. Dewhirst, F. E. Fox, J. G. TI HELICOBACTER CANIS COLONIZATION IN SHEEP: A ZOONOTIC LINK SO HELICOBACTER LA English DT Meeting Abstract CT 26th International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 12-14, 2013 CL Madrid, SPAIN SP European Helicobacter Study Grp C1 [Swennes, A. G.; Turk, M. L.; Trowel, E.; Cullin, C.; Pang, J. S.; Shen, Z.; Fox, J. G.] MIT, Cambridge, MA 02139 USA. [Dewhirst, F. E.] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD SEP PY 2013 VL 18 SU 1 SI SI BP 147 EP 147 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 213HT UT WOS:000324047300243 ER PT J AU Boussahmain, C Mochel, MC Hoang, MP AF Boussahmain, Chakib Mochel, Mark C. Hoang, Mai P. TI Perilipin and adipophilin expression in sebaceous carcinoma and mimics SO HUMAN PATHOLOGY LA English DT Article DE Adipophilin; Perilipin; Sebaceous carcinoma; Clear cell squamous cell carcinoma; Eccrine carcinoma; Apocrine carcinoma ID LIPID DROPLET PROTEINS; IMMUNOHISTOCHEMISTRY; FAMILY; TUMORS AB Although adipophilin has been reported to be a sensitive marker for sebaceous carcinoma, others have noted its expression in squamous cell carcinoma and a variety of noncutaneous tumors, suggesting that lipid droplet accumulation is a frequent feature of neoplastic cells. We investigated the expression of adipophilin and perilipin in 101 cutaneous carcinomas. They included 30 cases of sebaceous carcinoma, 28 squamous cell carcinoma with clear cell change (48 invasive and 10 in situ tumors), 8 hiciradenocarcinomas, 1 spiradenocarcinoma, 10 porocarcinomas, 4 malignant chondroid syringomas, 1 malignant cylindroma, 7 apocrine carcinomas, 6 eccrine carcinomas, 5 aggressive digital papillary adenocarcinomas, and 1 pilomatrical carcinoma. Adipophilin stained the rim of cytoplasmic lipid droplets in various tumor types, including sebaceous carcinomas (30/30, 100%), squamous cell carcinoma with clear cell change (21/28, 75%), and eccrine-apocrine carcinomas (25/43, 58%). On the other hand, perilipin expression was seen in 13 (43%) of 30 sebaceous carcinoma and only 1 hidradenocarcinoma. The remaining 28 squamous cell carcinomas with clear cell change and 42 eccrine-apocrine carcinomas were negative. Although specific for invasive sebaceous carcinoma, perilipin expression was not helpful in distinguishing sebaceous carcinoma in situ from squamous cell carcinoma in situ with clear cell change. The expression of adipophilin seen in variety of cutaneous tumors suggests that the biosynthesis of lipid is altered in these neoplasms. (C) 2013 Elsevier Inc. All rights reserved. C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM mhoang@partners.org NR 15 TC 12 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2013 VL 44 IS 9 BP 1811 EP 1816 DI 10.1016/j.humpath.2013.02.003 PG 6 WC Pathology SC Pathology GA 214RF UT WOS:000324152500015 PM 23642680 ER PT J AU Bui, E Orr, SP Jacoby, RJ Keshaviah, A LeBlanc, NJ Milad, MR Pollack, MH Simon, NM AF Bui, Eric Orr, Scott P. Jacoby, Ryan J. Keshaviah, Aparna LeBlanc, Nicole J. Milad, Mohammed R. Pollack, Mark H. Simon, Naomi M. TI Two weeks of pretreatment with escitalopram facilitates extinction learning in healthy individuals SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE posttraumatic stress disorder; acute stress disorder; prevention; SSRI; fear acquisition; extinction learning ID POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; MEDIAL PREFRONTAL CORTEX; EXPOSURE THERAPY; D-CYCLOSERINE; CONTROLLED-TRIAL; CITALOPRAM; AMYGDALA; ANXIETY; SYMPTOMS AB Objective We aimed to examine whether pretreatment with escitalopram would be associated with reduced fear acquisition and enhanced extinction learning in a fear conditioning paradigm, compared with placebo. Methods Healthy volunteers were randomized in double-blind fashion, to 14 days of escitalopram 10 mg/day (n = 18) or placebo (n = 20) prior to a classical fear conditioning paradigm. Results Although escitalopram was associated with a smaller skin conductance (SC) orienting response during habituation, no medication effects on fear acquisition were found. Escitalopram was associated with faster extinction of SC responses, compared with placebo, as revealed by a significant drug x conditioned stimulus x trial interaction for early extinction (F(3, 30) = 3.26, p = 0.035) and late extinction (F(3, 30) = 3.27, p = 0.035) trials. After adjustment for age, orienting response, and acquisition, results from linear contrast remained significant for early extinction (F(1, 29) = 5.43, p = 0.027). Conclusions Escitalopram administered for 14 days prior to a fear conditioning paradigm did not influence acquisition of a conditioned fear response but did facilitate extinction learning. Impairments in extinction learning have been identified as a key component of posttraumatic stress disorder; our preliminary findings suggest that additional experimental and clinical studies assessing the efficacy of selective serotonin reuptake inhibitors for posttraumatic stress disorder prevention are warranted. Copyright (C) 2013 John Wiley & Sons, Ltd. C1 [Bui, Eric; Orr, Scott P.; Jacoby, Ryan J.; Keshaviah, Aparna; LeBlanc, Nicole J.; Milad, Mohammed R.; Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Bui, Eric; Orr, Scott P.; Milad, Mohammed R.; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Bui, Eric] CHU Toulouse, Lab Stress Traumat EA4560, Toulouse, France. [Bui, Eric] Univ Toulouse 3, F-31062 Toulouse, France. [Pollack, Mark H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Pollack, Mark H.] Rush Med Coll, Chicago, IL 60612 USA. RP Bui, E (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq, Boston, MA 02114 USA. EM tebui@partners.org RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU Forest Pharmaceuticals [LXP-MD-139]; CHU de Toulouse; Association Traumapsy FX This study was funded by an investigator initiated grant from Forest Pharmaceuticals to Dr Simon and Dr Pollack (LXP-MD-139). Dr. Bui's effort was supported by a postdoctoral training fellowship from CHU de Toulouse and "Association Traumapsy." NR 45 TC 9 Z9 10 U1 5 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD SEP PY 2013 VL 28 IS 5 BP 447 EP 456 DI 10.1002/hup.2330 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 213HQ UT WOS:000324047000006 PM 23776033 ER PT J AU Smith, CE Ngwa, J Tanaka, T Qi, Q Wojczynski, MK Lemaitre, RN Anderson, JS Manichaikul, A Mikkila, V Van Rooij, FJA Ye, Z Bandinelli, S Frazier-Wood, AC Houston, DK Hu, F Langenberg, C McKeown, NM Mozaffarian, D North, KE Viikari, J Zillikens, MC Djousse, L Hofman, A Kahonen, M Kabagambe, EK Loos, RJF Saylor, GB Forouhi, NG Liu, Y Mukamal, KJ Chen, YDI Tsai, MY Uitterlinden, AG Raitakari, O Van Duijn, CM Arnett, DK Borecki, IB Cupples, LA Ferrucci, L Kritchevsky, SB Lehtimaki, T Qi, L Rotter, JI Siscovick, DS Wareham, NJ Witteman, JCM Ordovas, JM Nettleton, JA AF Smith, C. E. Ngwa, J. Tanaka, T. Qi, Q. Wojczynski, M. K. Lemaitre, R. N. Anderson, J. S. Manichaikul, A. Mikkila, V. Van Rooij, F. J. A. Ye, Z. Bandinelli, S. Frazier-Wood, A. C. Houston, D. K. Hu, F. Langenberg, C. McKeown, N. M. Mozaffarian, D. North, K. E. Viikari, J. Zillikens, M. C. Djousse, L. Hofman, A. Kahonen, M. Kabagambe, E. K. Loos, R. J. F. Saylor, G. B. Forouhi, N. G. Liu, Y. Mukamal, K. J. Chen, Y-D I. Tsai, M. Y. Uitterlinden, A. G. Raitakari, O. Van Duijn, C. M. Arnett, D. K. Borecki, I. B. Cupples, L. A. Ferrucci, L. Kritchevsky, S. B. Lehtimaki, T. Qi, Lu Rotter, J. I. Siscovick, D. S. Wareham, N. J. Witteman, J. C. M. Ordovas, J. M. Nettleton, J. A. TI Lipoprotein receptor-related protein 1 variants and dietary fatty acids: meta-analysis of European origin and African American studies SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE low-density lipoprotein receptor-related protein 1; SNPs; saturated fatty acids; gene-diet interactions ID GENE-ENVIRONMENT INTERACTIONS; OBESITY-ASSOCIATED GENE; WEIGHT-LOSS DIETS; ADIPOSE-TISSUE; BODY-WEIGHT; ASSOCIATION; MASS; EXPRESSION; COHORT; SAMPLE AB OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids. DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800). RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P - 0.0001), 0.267 cm for waist (interaction P = 0.001) and 0.21 cm for hip (interaction P = 0.001). No other significant interactions were observed. CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits. C1 [Smith, C. E.; McKeown, N. M.; Ordovas, J. M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA. [Ngwa, J.; Cupples, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Tanaka, T.; Ferrucci, L.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Qi, Q.; Hu, F.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Wojczynski, M. K.; Borecki, I. B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Lemaitre, R. N.] Univ Washington, Dept Med, Seattle, WA USA. [Anderson, J. S.; Saylor, G. B.] Wake Forest Sch Med, Cardiol Sect, Dept Internal Med, Winston Salem, NC USA. [Manichaikul, A.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaikul, A.] Univ Virginia, Div Biostat & Epidemiol, Charlottesville, VA USA. [Mikkila, V.] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Van Rooij, F. J. A.; Hofman, A.; Uitterlinden, A. G.; Van Duijn, C. M.; Witteman, J. C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Van Rooij, F. J. A.; Zillikens, M. C.; Hofman, A.; Uitterlinden, A. G.; Van Duijn, C. M.; Witteman, J. C. M.] NGI, NCHA, Leiden, Netherlands. [Ye, Z.; Langenberg, C.; Loos, R. J. F.; Forouhi, N. G.; Wareham, N. J.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Bandinelli, S.] Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy. [Frazier-Wood, A. C.; Kabagambe, E. K.; Arnett, D. K.] Univ Alabama Birmingham, Sect Stat Genet, Dept Epidemiol, Birmingham, AL USA. [Frazier-Wood, A. C.; Kabagambe, E. K.; Arnett, D. K.] Univ Alabama Birmingham, Off Energet, Birmingham, AL USA. [Houston, D. K.; Kritchevsky, S. B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Hu, F.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hu, F.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA USA. [Mozaffarian, D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mozaffarian, D.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Mozaffarian, D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Mozaffarian, D.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Mozaffarian, D.] Harvard Univ, Sch Med, Boston, MA USA. [North, K. E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, K. E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Viikari, J.] Univ Turku, Dept Med, Turku, Finland. [Viikari, J.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Zillikens, M. C.; Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Djousse, L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Djousse, L.] Boston VA Healthcare Syst, Boston, MA USA. [Kahonen, M.] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kahonen, M.] Tampere Univ Hosp, Tampere, Finland. [Liu, Y.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Mukamal, K. J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Chen, Y-D I.; Rotter, J. I.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Tsai, M. Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Raitakari, O.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, O.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Cupples, L. A.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Lehtimaki, T.] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, T.] Tampere Univ Hosp, Tampere, Finland. [Siscovick, D. S.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, D. S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Ordovas, J. M.] CNIC, Dept Epidemiol & Populat Genet, Madrid, Spain. [Ordovas, J. M.] Estudios Avanzados Alimentac, Inst Madrilenos, Madrid, Spain. [Nettleton, J. A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. RP Ordovas, JM (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, 711 Washington St, Boston, MA 02111 USA. EM jose.ordovas@tufts.edu RI Djousse, Luc/F-5033-2017; Wood, Lekki/B-8053-2010; OI Djousse, Luc/0000-0002-9902-3047; Wood, Lekki/0000-0001-7616-2119; Forouhi, Nita/0000-0002-5041-248X FU National Heart, Lung and Blood Institute [HHSN268 201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268 201100012C]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, UL1RR025005, HHSN268200782096C, HL71981, CA055075, CA87969, CA49449]; NIH Roadmap for Medical Research; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [5K01DK 082729-04]; NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129]; NIA [AG-023629, AG-15928, AG-20098, AG-027058, R01 AG032098]; National Center of Advancing Translational Technologies CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Medical Research Council; Cancer Research United Kingdom; Stroke Association; British Heart Foundation; Research Into Ageing; Academy of Medical Science; NIH from NHLBI [R01 HL087700, R01 HL088215]; NIDDK [R01 DK075681, R01 DK8925601]; Wellcome Trust; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; NIH/NIDDK [R01 DK089256-01]; USDA [58-1950-7-707]; US Department of Agriculture Research Service [53-K06-5-10, 58-1950-9-001]; Intramural Research Program of the NIH, National Institute on Aging [N01AG62101, N01AG62103, N01AG62106]; American Heart Association [0730094N]; Italian Ministry of Health; US National Institute on Aging [263 MD 9164, 263 MD 821336]; National Heart, Lung and Blood Institute (NHLBI) [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, RR-024156]; Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission; Municipality of Rotterdam; Academy of Finland [126925, 121584, 124282, 129378, 117787, 41071]; Social Insurance Institution of Finland, Kuopio, Tampere; Turku University Hospital Medical Funds [9M048, 9N035]; Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular Research; Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; NHLBI. [N02-HL-6-4278, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, R01-HL085251, HL087652, HL105756, N01-HC-25195, U01-HL072524]; [R01HL087641]; [R01HL59367]; [R01HL086694]; [P50 HL105185-01]; [ICS110.1/RF97.71]; [R01HL071051]; [R01HL071205]; [R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL 071258]; [R01HL071259] FX The Atherosclerosis Risk In Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung and Blood Institute contracts (HHSN268 201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268 201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. We the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Dr Nettleton is supported by a K01 from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK 082729-04). Cardiovascular Health Study (CHS) research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C and NHLBI grants HL080295, R01-HL085251 HL087652, HL105756 with additional contribution from NINDS. Additional support was provided through AG-023629, AG-15928, AG-20098 and AG-027058 from the NIA. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by National Center of Advancing Translational Technologies CTSI grant UL1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. European Prospective Investigation of Cancer Norfolk (EPIC Norfolk): EPIC-Norfolk is supported by grant funding from the Medical Research Council and Cancer Research United Kingdom with additional support from the Stroke Association, British Heart Foundation, Research Into Ageing and the Academy of Medical Science. The Family Heart Study (FamHS) work was supported by NIH grants R01 HL087700, R01 HL088215 (Michael A. Province) from NHLBI; and R01 DK075681 and R01 DK8925601 from NIDDK (Ingrid B. Borecki). The investigators thank the staff and participants of the FamHS for their important contributions. The Fenland Study is funded by the Wellcome Trust and the Medical Research Council. We are grateful to all the volunteers for their time and help and to the General Practitioners and practice staff for help with recruitment. We thank the Fenland Study co-ordination team, the Field Epidemiology team and the Fenland Study investigators. Biochemical assays were performed by the National Institute for Health Research, Cambridge Biomedical Research Centre, Core Biochemistry Assay Laboratory and the Cambridge University Hospitals NHS Foundation Trust. The Framingham Offspring Study and Framingham Third Generation Study (FHS) were conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc., for genotyping services (Contract No. N02-HL-6-4278).; A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Dr Cupples and Mr Ngwa are partially supported by NIH/NIDDK grant R01 DK089256-01. Dr Nicola McKeown is supported by the USDA agreement No. 58-1950-7-707. The GOLDN (Genetics of Lipid Lowering Drugs and Diet Network) study was funded by the National Heart, Lung and Blood Institute Grant No. U01-HL072524, Genetic and Environmental Determinants of Triglycerides. Dr Smith and Dr Ordovas are partially supported by P50 HL105185-01 and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service. The Health, Aging and Body Composition (Health ABC) study was supported in part by the Intramural Research Program of the NIH, National Institute on Aging contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA grant R01 AG032098 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. Health Professionals Follow-up Study (HPFS): The HPFS was supported by grants HL71981 and CA055075 from the National Institutes of Health. Dr Lu Qi is a recipient of the American Heart Association Scientist Development Award (0730094N). We thank the participants of the HPFS for their continued cooperation. Invecchiare in Chianti (aging in the Chianti area, InCHIANTI) study investigators thank the Intramural Research Program of the NIH, National Institute on Aging who are responsible for the InCHIANTI samples. Investigators also thank the InCHIANTI participants. The InCHIANTI study baseline (1998-2000) was supported as a 'targeted project' (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the US National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336). MESA and the MESA SHARe project are conducted and supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the National Heart, Lung and Blood Institute (NHLBI). Funding for MESA SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL 071258, R01HL071259. We thank the participants of the MESA study, the Coordinating Center, MESA investigators, and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Nurses Health Study (NHS): The NHS was supported by grants HL71981, CA87969 and CA49449 from the National Institutes of Health. Dr Lu Qi is a recipient of the American Heart Association Scientist Development Award (0730094N). We thank the participants of the NHS for their continued cooperation. Rotterdam Study: The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810.; We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating the GWAS database, and Karol Estrada and Maksim V. Struchalin for their support in creation and analysis of imputed data. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. We are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. Young Finns Study: The Young Finns Study has been financially supported by the Academy of Finland: grants 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi) and 41071 (Skidi), the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds (grant 9M048 and 9N035 for TeLeht), Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, Tampere Tuberculosis Foundation and Emil Aaltonen Foundation (T. L). The authors gratefully acknowledge the statistical analyses provided by Ville Aalto. NR 39 TC 3 Z9 3 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2013 VL 37 IS 9 BP 1211 EP 1220 DI 10.1038/ijo.2012.215 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 216QX UT WOS:000324300100008 PM 23357958 ER PT J AU Chung, CS Yock, TI Nelson, K Xu, Y Keating, NL Tarbell, NJ AF Chung, Christine S. Yock, Torunn I. Nelson, Kerrie Xu, Yang Keating, Nancy L. Tarbell, Nancy J. TI Incidence of Second Malignancies Among Patients Treated With Proton Versus Photon Radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID THERAPY; CANCERS; RISK; RADIOTHERAPY; NEUTRONS; LYMPHOMA; TUMORS AB Purpose: Proton radiation, when compared with photon radiation, allows delivery of increased radiation dose to the tumor while decreasing dose to adjacent critical structures. Given the recent expansion of proton facilities in the United States, the long-term sequelae of proton therapy should be carefully assessed. The objective of this study was to compare the incidence of second cancers in patients treated with proton radiation with a population-based cohort of matched patients treated with photon radiation. Methods and Materials: We performed a retrospective cohort study of 558 patients treated with proton radiation from 1973 to 2001 at the Harvard Cyclotron in Cambridge, MA and 558 matched patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Patients were matched by age at radiation treatment, sex, year of treatment, cancer histology, and site. The main outcome measure was the incidence of second malignancies after radiation. Results: We matched 558 proton patients with 558 photon patients from the Surveillance, Epidemiology, and End Results registry. The median duration of follow-up was 6.7 years (interquartile range, 7.4) and 6.0 years (interquartile range, 9.3) in the proton and photon cohorts, respectively. The median age at treatment was 59 years in each cohort. Second malignancies occurred in 29 proton patients (5.2%) and 42 photon patients (7.5%). After we adjusted for sex, age at treatment, primary site, and year of diagnosis, proton therapy was not associated with an increased risk of second malignancy (adjusted hazard ratio, 0.52 [95% confidence interval, 0.32-0.85]; P = .009). Conclusions: The use of proton radiation therapy was not associated with a significantly increased risk of secondary malignancies compared with photon therapy. Longer follow-up of these patients is needed to determine if there is a significant decrease in second malignancies. Given the limitations of the study, these results should be viewed as hypothesis generating. (C) 2013 Elsevier Inc. C1 [Chung, Christine S.] Alta Bates Summit Med Ctr, Dept Radiat Oncol, Berkeley, CA USA. [Yock, Torunn I.; Tarbell, Nancy J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Nelson, Kerrie] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Xu, Yang; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Tarbell, Nancy J.] Harvard Univ, Sch Med, Off Execut Dean, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Gen Internal Med, Boston, MA 02115 USA. RP Chung, CS (reprint author), Alta Bates Comprehens Canc Ctr, 2001 Dwight Way, Berkeley, CA 94705 USA. EM chungc1@sutterhealth.org NR 20 TC 57 Z9 57 U1 0 U2 11 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 SEP 1 PY 2013 VL 87 IS 1 BP 46 EP 52 DI 10.1016/j.ijrobp.2013.04.030 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 216UE UT WOS:000324309500013 PM 23778197 ER PT J AU Han, K Milosevic, M Fyles, A Pintilie, M Viswanathan, AN AF Han, Kathy Milosevic, Michael Fyles, Anthony Pintilie, Melania Viswanathan, Akila N. TI Trends in the Utilization of Brachytherapy in Cervical Cancer in the United States SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID MODULATED RADIATION-THERAPY; UTERINE CERVIX; RADIOTHERAPY PRACTICE; NATIONAL PRACTICE; BREAST-CANCER; PATTERNS; CARE; CARCINOMA; SURVIVAL AB Purpose: To determine the trends in brachytherapy use in cervical cancer in the United States and to identify factors and survival benefits associated with brachytherapy treatment. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 7359 patients with stages IB2-IVA cervical cancer treated with external beam radiation therapy (EBRT) between 1988 and 2009. Propensity score matching was used to adjust for differences between patients who received brachytherapy and those who did not from 2000 onward (after the National Cancer Institute alert recommending concurrent chemotherapy). Results: Sixty-three percent of the 7359 women received brachytherapy in combination with EBRT, and 37% received EBRT alone. The brachytherapy utilization rate has decreased from 83% in 1988 to 58% in 2009 (P<.001), with a sharp decline of 23% in 2003 to 43%. Factors associated with higher odds of brachytherapy use include younger age, married (vs single) patients, earlier years of diagnosis, earlier stage and certain SEER regions. In the propensity score-matched cohort, brachytherapy treatment was associated with higher 4-year cause-specific survival (CSS; 64.3% vs 51.5%, P<.001) and overall survival (OS; 58.2% vs 46.2%, P<.001). Brachytherapy treatment was independently associated with better CSS (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.57-0.71), and OS (HR 0.66; 95% CI, 0.60 to 0.74). Conclusions: This population-based analysis reveals a concerning decline in brachytherapy utilization and significant geographic disparities in the delivery of brachytherapy in the United States. Brachytherapy use is independently associated with significantly higher CSS and OS and should be implemented in all feasible cases. (C) 2013 Elsevier Inc. C1 [Han, Kathy; Milosevic, Michael; Fyles, Anthony] Univ Hlth Network, Princess Margaret Hosp, Radiat Med Program, Toronto, ON, Canada. [Pintilie, Melania] Princess Margaret Hosp, Dept Biostat, Toronto, ON M5G 2M9, Canada. [Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Han, K (reprint author), Princess Margaret Hosp, Dept Radiat Oncol, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM Kathy.Han@rmp.uhn.on.ca OI Viswanathan, Akila/0000-0002-2003-0392; Fyles, Anthony/0000-0002-3633-2483 FU Canadian Association of Radiation Oncology-Elekta fellowship; Canadian Institute of Health/Terry Fox Foundation Research Excellence in Radiation Research FX Dr Han received fellowship salary support from the Canadian Association of Radiation Oncology-Elekta fellowship and a Canadian Institute of Health/Terry Fox Foundation Research Excellence in Radiation Research for the 21st Century award. NR 21 TC 83 Z9 83 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2013 VL 87 IS 1 BP 111 EP 119 DI 10.1016/j.ijrobp.2013.05.033 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 216UE UT WOS:000324309500023 PM 23849695 ER PT J AU Jimenez, RB Sethi, R Depauw, N Pulsifer, MB Adams, J McBride, SM Ebb, D Fullerton, BC Tarbell, NJ Yock, TI MacDonald, SM AF Jimenez, Rachel B. Sethi, Roshan Depauw, Nicolas Pulsifer, Margaret B. Adams, Judith McBride, Sean M. Ebb, David Fullerton, Barbara C. Tarbell, Nancy J. Yock, Torunn I. MacDonald, Shannon M. TI Proton Radiation Therapy for Pediatric Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumors: Outcomes for Very Young Children Treated With Upfront Chemotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID EARLY-CHILDHOOD MEDULLOBLASTOMA; POSTOPERATIVE CHEMOTHERAPY; PROSPECTIVE TRIAL; BRAIN-TUMORS; RADIOTHERAPY AB Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients had medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity. (C) 2013 Elsevier Inc. C1 [Jimenez, Rachel B.; McBride, Sean M.] Harvard Radiat Oncol Program, Boston, MA USA. [Sethi, Roshan] Harvard Univ, Sch Med, Boston, MA USA. [Depauw, Nicolas; Adams, Judith; Fullerton, Barbara C.; Tarbell, Nancy J.; Yock, Torunn I.; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ebb, David] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Jimenez, RB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 54 Fruit St, Boston, MA 02114 USA. EM rbjimenez@partners.org NR 20 TC 18 Z9 19 U1 0 U2 7 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 SEP 1 PY 2013 VL 87 IS 1 BP 120 EP 126 DI 10.1016/j.ijrobp.2013.05.017 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 216UE UT WOS:000324309500024 PM 23790826 ER PT J AU Seco, J Gu, G Marcelos, T Kooy, H Willers, H AF Seco, Joao Gu, Guan Marcelos, Tiago Kooy, Hanne Willers, Henning TI Proton Arc Reduces Range Uncertainty Effects and Improves Conformality Compared With Photon Volumetric Modulated Arc Therapy in Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADIOTHERAPY; CARCINOMA; SBRT AB Purpose: To describe, in a setting of non-small cell lung cancer (NSCLC), the theoretical dosimetric advantages of proton arc stereotactic body radiation therapy (SBRT) in which the beam penumbra of a rotating beam is used to reduce the impact of range uncertainties. Methods and Materials: Thirteen patients with early-stage NSCLC treated with proton SBRT underwent repeat planning with photon volumetric modulated arc therapy (Photon-VMAT) and an in-house-developed arc planning approach for both proton passive scattering (Passive-Arc) and intensity modulated proton therapy (IMPT-Arc). An arc was mimicked with a series of beams placed at 10 degrees increments. Tumor and organ at risk doses were compared in the context of high-and low-dose regions, represented by volumes receiving >50% and <50% of the prescription dose, respectively. Results: In the high-dose region, conformality index values are 2.56, 1.91, 1.31, and 1.74, and homogeneity index values are 1.29, 1.22, 1.52, and 1.18, respectively, for 3 proton passive scattered beams, Passive-Arc, IMPT-Arc, and Photon-VMAT. Therefore, proton arc leads to a 30% reduction in the 95% isodose line volume to 3-beam proton plan, sparing surrounding organs, such as lung and chest wall. For chest wall, V30 is reduced from 21 cm(3) (3 proton beams) to 11.5 cm(3), 12.9 cm(3), and 8.63 cm(3) (P = .005) for Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. In the low-dose region, the mean lung dose and V20 of the ipsilateral lung are 5.01 Gy(relative biological effectiveness [RBE]), 4.38 Gy(RBE), 4.91 Gy(RBE), and 5.99 Gy(RBE) and 9.5%, 7.5%, 9.0%, and 10.0%, respectively, for 3-beam, Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. Conclusions: Stereotactic body radiation therapy with proton arc and Photon-VMAT generate significantly more conformal high-dose volumes than standard proton SBRT, without loss of coverage of the tumor and with significant sparing of nearby organs, such as chest wall. In addition, both proton arc approaches spare the healthy lung from low-dose radiation relative to photon VMAT. Our data suggest that IMPT-Arc should be developed for clinical use. (C) 2013 Elsevier Inc. C1 [Seco, Joao; Gu, Guan; Marcelos, Tiago; Kooy, Hanne; Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Seco, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 315, Boston, MA 02114 USA. EM jseco@partners.org NR 17 TC 11 Z9 12 U1 1 U2 4 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 SEP 1 PY 2013 VL 87 IS 1 BP 188 EP 194 DI 10.1016/j.ijrobp.2013.04.048 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 216UE UT WOS:000324309500034 PM 23920395 ER PT J AU Giantsoudi, D Grassberger, C Craft, D Niemierko, A Trofimov, A Paganetti, H AF Giantsoudi, Drosoula Grassberger, Clemens Craft, David Niemierko, Andrzej Trofimov, Alexei Paganetti, Harald TI Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID BIOLOGICAL EFFECTIVENESS; BEAM THERAPY AB Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose-volume and LET-volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution. (C) 2013 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Giantsoudi, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM dgiantsoudi@partners.org FU Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX Supported by the federal share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 9 TC 33 Z9 33 U1 0 U2 12 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 SEP 1 PY 2013 VL 87 IS 1 BP 216 EP 222 DI 10.1016/j.ijrobp.2013.05.013 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 216UE UT WOS:000324309500038 PM 23790771 ER PT J AU Phelan, E Kamanai, D Shin, J Randolph, G AF Phelan, E. Kamanai, D. Shin, J. Randolph, G. TI Neural Monitored Revision Thyroid Cancer Surgery-Surgical Safety and Thyroglobulin Response SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Phelan, E.; Kamanai, D.; Shin, J.; Randolph, G.] Mass Eye Ear Infirm, Dept Otolaryngol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD SEP PY 2013 VL 182 SU 7 MA 42 BP S333 EP S333 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 217CX UT WOS:000324335400043 ER PT J AU Makarov, DV Loeb, S Ulmert, D Drevin, L Lambe, M Stattin, P AF Makarov, Danil V. Loeb, Stacy Ulmert, David Drevin, Linda Lambe, Mats Stattin, Par TI Prostate Cancer Imaging Trends After a Nationwide Effort to Discourage Inappropriate Prostate Cancer Imaging SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STAGING EVALUATION; BONE-SCAN; APPROPRIATE; ANTIGEN; RISK; PREVALENCE; GUIDELINES; PARAMETERS; SURVIVAL; OVERUSE AB Background Reducing inappropriate use of imaging to stage incident prostate cancer is a challenging problem highlighted recently as a Physician Quality Reporting System quality measure and by the American Society of Clinical Oncology and the American Urological Association in the Choosing Wisely campaign. Since 2000, the National Prostate Cancer Register (NPCR) of Sweden has led an effort to decrease national rates of inappropriate prostate cancer imaging by disseminating utilization data along with the latest imaging guidelines to urologists in Sweden. We sought to determine the temporal and regional effects of this effort on prostate cancer imaging rates. Methods We performed a retrospective cohort study among men diagnosed with prostate cancer from the NPCR from 1998 to 2009 (n = 99 879). We analyzed imaging use over time stratified by clinical risk category (low, intermediate, high) and geographic region. Generalized linear models with a logit link were used to test for time trend. Results Thirty-six percent of men underwent imaging within 6 months of prostate cancer diagnosis. Overall, imaging use decreased over time, particularly in the low-risk category, among whom the imaging rate decreased from 45% to 3% (P < .001), but also in the high-risk category, among whom the rate decreased from 63% to 47% (P < .001). Despite substantial regional variation, all regions experienced clinically and statistically (P < .001) significant decreases in prostate cancer imaging. Conclusions A Swedish effort to provide data on prostate cancer imaging use and imaging guidelines to clinicians was associated with a reduction in inappropriate imaging over a 10-year period, as well as slightly decreased appropriate imaging in high-risk patients. These results may inform current efforts to promote guideline-concordant imaging in the United States and internationally. C1 [Makarov, Danil V.; Loeb, Stacy] US Dept Vet Affairs, New York, NY USA. [Makarov, Danil V.; Loeb, Stacy] NYU, Dept Urol, New York, NY USA. [Makarov, Danil V.; Loeb, Stacy] NYU, Dept Populat Hlth, New York, NY USA. [Makarov, Danil V.; Loeb, Stacy] NYU, Inst Canc, New York, NY USA. [Drevin, Linda; Lambe, Mats] Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden. [Ulmert, David; Stattin, Par] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. [Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, SE-90187 Umea, Sweden. [Lambe, Mats] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Stattin, P (reprint author), Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, SE-90187 Umea, Sweden. EM par.stattin@urologi.umu.se OI Lambe, Mats/0000-0002-4624-3767; Makarov, Danil/0000-0002-0565-9272; Loeb, Stacy/0000-0003-3933-9207 FU Swedish Research Council [825-2012-5047]; Swedish Cancer Foundation [11 0471]; United States Department of Veterans Affairs, Health Services Research and Development Service; Louis Feil Charitable Lead Trust FX This work was supported by the Swedish Research Council (825-2012-5047) and The Swedish Cancer Foundation (11 0471). SL and DVM (VA HSR&D CDA & CDP 11-257) are supported by the United States Department of Veterans Affairs, Health Services Research and Development Service and the Louis Feil Charitable Lead Trust. NR 32 TC 14 Z9 14 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD SEP PY 2013 VL 105 IS 17 BP 1306 EP 1313 DI 10.1093/jnci/djt175 PG 8 WC Oncology SC Oncology GA 213EW UT WOS:000324038500011 PM 23853055 ER PT J AU Tannous, BA Kerami, M Van der Stoop, PM Kwiatkowski, N Wang, JH Zhou, WJ Kessler, AF Lewandrowski, G Hiddingh, L Sol, N Lagerweij, T Wedekind, L Niers, JM Barazas, M Nilsson, RJA Geerts, D Hamer, PCD Hagemann, C Vandertop, WP Van Tellingen, O Noske, DP Gray, NS Wurdinger, T AF Tannous, Bakhos A. Kerami, Mariam Van der Stoop, Petra M. Kwiatkowski, Nicholas Wang, Jinhua Zhou, Wenjun Kessler, Almuth F. Lewandrowski, Grant Hiddingh, Lotte Sol, Nik Lagerweij, Tonny Wedekind, Laurine Niers, Johanna M. Barazas, Marco Nilsson, R. Jonas A. Geerts, Dirk Hamer, Philip C. De Witt Hagemann, Carsten Vandertop, W. Peter Van Tellingen, Olaf Noske, David P. Gray, Nathanael S. Wuerdinger, Thomas TI Effects of the Selective MPS1 Inhibitor MPS1-IN-3 on Glioblastoma Sensitivity to Antimitotic Drugs SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN CANCER-CELLS; SMALL-MOLECULE INHIBITOR; MITOTIC CHECKPOINT; SPINDLE-CHECKPOINT; MICROTUBULE DYNAMICS; KINASE; MITOSIS; MECHANISM; GLIOMA; PROLIFERATION AB Background Glioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest. Methods We used glioblastoma cells to determine the expression of MPS1 and to determine the effects of MPS1 inhibition on mitotic errors and cell viability in combination with vincristine and taxol. The effect of MPS1 inhibition was assessed in different orthotopic glioblastoma mouse models (n = 3-7 mice/group). MPS1 expression levels were examined in relation to patient survival. Results Using publicly available gene expression data, we determined that MPS1 overexpression corresponds positively with tumor grade and negatively with patient survival (two-sided t test, P < .001). Patients with high MPS1 expression (n = 203) had a median and mean survival of 487 and 913 days (95% confidence intervals [CI] = 751 to 1075), respectively, and a 2-year survival rate of 35%, whereas patients with intermediate MPS1 expression (n = 140) had a median and mean survival of 858 and 1183 days (95% CI = 1177 to 1189), respectively, and a 2-year survival rate of 56%. We demonstrate that MPS1 inhibition by RNAi results in sensitization to antimitotic agents. We developed a selective small-molecule inhibitor of MPS1, MPS1-IN-3, which caused mitotic aberrancies in glioblastoma cells and, in combination with vincristine, induced mitotic checkpoint override, increased aneuploidy, and augmented cell death. MPS1-IN-3 sensitizes glioblastoma cells to vincristine in orthotopic mouse models (two-sided log-rank test, P < .01), resulting in prolonged survival without toxicity. Conclusions Our results collectively demonstrate that MPS1, a putative therapeutic target in glioblastoma, can be selectively inhibited by MPS1-IN-3 sensitizing glioblastoma cells to antimitotic drugs. C1 [Tannous, Bakhos A.; Kerami, Mariam; Lewandrowski, Grant; Barazas, Marco; Wuerdinger, Thomas] Harvard Univ, Sch Med, Dept Neurol, Neurosci Ctr, Boston, MA 02115 USA. [Tannous, Bakhos A.; Kerami, Mariam; Lewandrowski, Grant; Barazas, Marco; Wuerdinger, Thomas] Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02115 USA. [Tannous, Bakhos A.; Kerami, Mariam; Lewandrowski, Grant; Barazas, Marco; Wuerdinger, Thomas] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Tannous, Bakhos A.; Kerami, Mariam; Lewandrowski, Grant; Barazas, Marco; Wuerdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Kerami, Mariam; Van der Stoop, Petra M.; Hiddingh, Lotte; Sol, Nik; Wedekind, Laurine; Niers, Johanna M.; Barazas, Marco; Nilsson, R. Jonas A.; Hamer, Philip C. De Witt; Vandertop, W. Peter; Noske, David P.; Wuerdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands. [Kwiatkowski, Nicholas; Wang, Jinhua; Zhou, Wenjun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kwiatkowski, Nicholas; Wang, Jinhua; Zhou, Wenjun; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kessler, Almuth F.; Hagemann, Carsten] Univ Wurzburg, Tumorbiol Lab, Dept Neurosurg, D-97070 Wurzburg, Germany. [Nilsson, R. Jonas A.] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Geerts, Dirk] Erasmus Univ, Med Ctr, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. [Van Tellingen, Olaf] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Clin Chem Preclin Pharmacol, Amsterdam, Netherlands. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam Med Ctr, CCA Room 3-34,Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM t.wurdinger@vumc.nl RI De Witt Hamer, Philip/E-7630-2013; OI Lagerweij, Tonny/0000-0003-1043-7452; De Witt Hamer, Philip/0000-0003-2988-8544; Geerts, Dirk/0000-0002-6386-8187 FU National Institues of Health/National Institute of Neurological Disorders and Stroke [1R01NS064983]; STOPhersentumoren.nl; NWO-VIDI; National Institutes of Health [U54 HG006097-02] FX This work was supported partly by the National Institues of Health/National Institute of Neurological Disorders and Stroke (1R01NS064983 to BAT); STOPhersentumoren.nl (to PMVdS); NWO-VIDI (to TW); and the National Institutes of Health (U54 HG006097-02 to NSG). NR 43 TC 25 Z9 25 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD SEP PY 2013 VL 105 IS 17 BP 1322 EP 1331 DI 10.1093/jnci/djt168 PG 10 WC Oncology SC Oncology GA 213EW UT WOS:000324038500013 PM 23940287 ER PT J AU Rae, JM Regan, MM Thibert, JN Gersch, C Thomas, D Leyland-Jones, B Viale, G Pusztai, L Hayes, DF Skaar, T Van Poznak, C AF Rae, James M. Regan, Meredith M. Thibert, Jacklyn N. Gersch, Christina Thomas, Dafydd Leyland-Jones, Brian Viale, Giuseppe Pusztai, Lajos Hayes, Daniel F. Skaar, Todd Van Poznak, Catherine TI Concordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Germline DNA SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RESPONSIVE BREAST-CANCER; GROUP 1-98 TRIAL; POSTMENOPAUSAL WOMEN; TAMOXIFEN RESPONSE; RE CYP2D6; ADJUVANT TAMOXIFEN; UGT2B7 GENOTYPE; RECURRENCE; INHIBITION; METABOLISM AB Formalin-fixed, paraffin-embedded tumors (FFPETs) are a valuable source of DNA for genotype association studies and are often the only germline DNA resource from cancer clinical trials. The anti-estrogen tamoxifen is metabolized into endoxifen by CYP2D6, leading to the hypothesis that patients with certain CYP2D6 genotypes may not receive benefit because of their inability to activate the drug. Studies testing this hypothesis using FFPETs have provided conflicting results. It has been postulated that CYP2D6 genotype determined using FFPET may not be accurate because of somatic tumor alterations. In this study, we determined the concordance between CYP2D6 genotypes generated using 3 tissue sources (FFPETs; formalin-fixed, paraffin-embedded unaffected lymph nodes [FFPELNs]; and whole blood cells [WBCs]) from 122 breast cancer patients. Compared with WBCs, FFPET and FFPELN genotypes were highly concordant (>94%), as were the predicted CYP2D6 metabolic phenotypes (>97%). We conclude that CYP2D6 genotypes obtained from FFPETs accurately represent the patient's CYP2D6 metabolic phenotype. C1 [Rae, James M.; Thibert, Jacklyn N.; Gersch, Christina; Thomas, Dafydd; Hayes, Daniel F.; Van Poznak, Catherine] Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA. [Rae, James M.; Hayes, Daniel F.; Van Poznak, Catherine] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Rae, James M.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Thomas, Dafydd] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. [Leyland-Jones, Brian] Sanford Hlth & Res, Sioux Falls, SD USA. [Viale, Giuseppe; Skaar, Todd] Univ Milan, Milan, Italy. [Pusztai, Lajos] Yale Univ, Sch Med, New Haven, CT USA. [Skaar, Todd] Indiana Univ, Div Clin Pharmacol, Indianapolis, IN 46204 USA. RP Rae, JM (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Div Hematol Oncol, 1500 E Med Ctr Dr,6310 Canc Ctr, Ann Arbor, MI 48109 USA. EM jimmyrae@umich.edu FU Breast Cancer Research Foundation (BCRF) [N003173, 1RO1GM099143, 5K23DE020197, UL1RR024986, KG080081, 5U24CA075362] FX This work was supported in part by the Breast Cancer Research Foundation (BCRF) (N003173 to JMR and DFH; 1RO1GM099143 to JMR; 5K23DE020197 and UL1RR024986 to CVP; KG080081 to GV and MMR; and 5U24CA075362 to MMR). NR 22 TC 20 Z9 20 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP PY 2013 VL 105 IS 17 BP 1332 EP 1334 DI 10.1093/jnci/djt204 PG 3 WC Oncology SC Oncology GA 213EW UT WOS:000324038500014 PM 23958736 ER PT J AU Yarar-Fisher, C Bickel, CS Windham, ST McLain, AB Bamman, MM AF Yarar-Fisher, Ceren Bickel, C. Scott Windham, Samuel T. McLain, Amie B. Bamman, Marcas M. TI Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE spinal cord injury; skeletal muscle; glucose uptake signaling; neuromuscular electrical stimulation; resistance exercise ID ACTIVATED PROTEIN-KINASE; RESISTANCE EXERCISE; INSULIN SENSITIVITY; LIPID-METABOLISM; OLDER-ADULTS; MOLECULAR RESPONSES; AKT SUBSTRATE; TIME-COURSE; AMPK; PHOSPHORYLATION AB The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI (n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and approximate to 90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated-and total AMP-activated protein kinase (AMPK)-alpha, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher (P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower (P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-alpha, CaMKII, and Akt (P < 0.05), and Akt phosphorylation increased robustly (P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-alpha, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even approximate to 22 yr after injury. C1 [Yarar-Fisher, Ceren; Bamman, Marcas M.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA. [Bickel, C. Scott] Univ Alabama Birmingham, Dept Phys Therapy, Birmingham, AL 35294 USA. [Windham, Samuel T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [McLain, Amie B.] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL 35294 USA. [Yarar-Fisher, Ceren; Bickel, C. Scott; Windham, Samuel T.; McLain, Amie B.; Bamman, Marcas M.] Univ Alabama Birmingham, UAB Ctr Exercise Med, Birmingham, AL 35294 USA. [Bamman, Marcas M.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Bamman, MM (reprint author), Univ Alabama Birmingham, UAB Ctr Exercise Med, 966 McCallum Basic Hlth Sci Bldg,1720 2nd Ave Sou, Birmingham, AL 35294 USA. EM mbamman@uab.edu FU VA Merit Award; University of Alabama Birmingham (UAB) Center for Exercise Medicine, Department of Physical Medicine and Rehabilitation [5T32 DK-62710]; UAB Center for Clinical and Translational Science [UL1 TR000165] FX This work was supported by VA Merit Award (M. M. Bamman), University of Alabama Birmingham (UAB) Center for Exercise Medicine, Department of Physical Medicine and Rehabilitation, 5T32 DK-62710, and the UAB Center for Clinical and Translational Science (UL1 TR000165). NR 52 TC 3 Z9 3 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2013 VL 115 IS 5 BP 756 EP 764 DI 10.1152/japplphysiol.00122.2013 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 212YZ UT WOS:000324020600023 PM 23766505 ER PT J AU Carroll, BJ Contreras-Valdes, FM Heist, EK Barrett, CD Danik, SB Ruskin, JN Mansour, M AF Carroll, Brett J. Contreras-Valdes, Fernando M. Heist, E. Kevin Barrett, Conor D. Danik, Stephan B. Ruskin, Jeremy N. Mansour, Moussa TI Multi-Sensor Esophageal Temperature Probe Used During Radiofrequency Ablation for Atrial Fibrillation is Associated with Increased Intraluminal Temperature Detection and Increased Risk of Esophageal Injury Compared to Single-Sensor Probe SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; complications; electrophysiology; esophageal injury; esophageal temperature monitoring; pulmonary vein isolation ID PULMONARY VEIN ISOLATION; CATHETER ABLATION; ROBOTIC NAVIGATION; PREVALENCE; FISTULA; LESIONS; DAMAGE; TIP AB Single vs Multi-Sensor ETM in AF Ablation. Background: Radiofrequency (RF) ablation in the posterior left atrium has risk of thermal injury to the adjacent esophagus. Increased intraluminal esophageal temperature has been correlated with risk of esophageal injury. The objective of this study was to compare esophageal temperature monitoring (ETM) using a multi-sensor temperature probe with 12 sensors to a single-sensor probe during catheter ablation for atrial fibrillation (AF). Methods and Results: We compared the detection of intraluminal esophageal temperature rises in 543 patients undergoing RF ablation for AF with ETM. Esophageal endoscopy (EGD) was performed on all patients with maximum esophageal temperature >= 39 degrees C. Esophageal lesions were classified by severity as mild or severe ulcerations. Four hundred fifty-five patients underwent RF ablation with single-sensor ETM and 88 patients with multi-sensor ETM. Thirty-nine percent of patients with single-sensor versus 75% with multi-sensor ETM reached a maximum detected esophageal temperature >= 39 degrees C (P < 0.0001). Esophageal injury was detected by EGD in 29% of patients with maximum temperature >= 39 degrees C by single-sensor versus 46% of patients with multi-sensor ETM (P = 0.021). Thirty-nine percent of patients with lesions in the single-sensor probe group had severe ulcerations compared to 33% of patients in the multi-sensor probe group (P = 0.641). Conclusions: Intraluminal esophageal temperature >= 39 degrees C is detected more frequently by the multi-sensor temperature probe versus the single-sensor probe, with more frequent esophageal injury and with comparable severity of injury. Despite detecting esophageal temperature rises in more patients, the multi-sensor probe may not have any measurable benefit compared to a single-sensor probe. C1 [Carroll, Brett J.; Contreras-Valdes, Fernando M.] Harvard Univ, Sch Med, Dept Med, Cardiac Arrhythmia Serv,Massachusetts Gen Hosp, Boston, MA USA. [Heist, E. Kevin; Barrett, Conor D.; Danik, Stephan B.; Ruskin, Jeremy N.; Mansour, Moussa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Heart Ctr,Cardiac Arrhythmia Serv, Boston, MA USA. RP Mansour, M (reprint author), 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM mmansour@partners.org FU Boston Scientific; Sorin; Biosense Webster; Medtronic; St. Jude Medical; MC 10; Voyage Medical; Rhythmia Medical FX Dr. Heist has served as a consultant for Biosense Webster, Boston Scientific, Sanofi-Aventis, Sorin, and St. Jude Medical, and has received research grants from Boston Scientific and Sorin. Dr. Ruskin has served as a consultant for Advanced Medical Education, Astellas/Cardiome, Atricure, Biosense Webster, Bristol-Myers Squibb, Medtronic, Pfizer, Portola, Sanofi-Aventis, and Third Rock Ventures; has received fellowship support from Biosense Webster, Boston Scientific, Medtronic, and St. Jude Medical; has served on the clinical oversight committee for CardioFocus; has served on the scientific advisory board for CardioInsight and InfoBionic; has equity with Portola; and has served on the scientific steering committee for Pfizer. Dr. Mansour has received research grants from Biosense Webster, Boston Scientific, St. Jude Medical, MC 10, Voyage Medical, and Rhythmia Medical, and has served as a consultant for Biosense Webster and St. Jude Medical. Other authors: No disclosures. NR 28 TC 14 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2013 VL 24 IS 9 BP 958 EP 964 DI 10.1111/jce.12180 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213LZ UT WOS:000324060000002 PM 23746064 ER PT J AU Lin, AL Zheng, W Halloran, JJ Burbank, RR Hussong, SA Hart, MJ Javors, M Shih, YYI Muir, E Fonseca, RS Strong, R Richardson, AG Lechleiter, JD Fox, PT Galvan, V AF Lin, Ai-Ling Zheng, Wei Halloran, Jonathan J. Burbank, Raquel R. Hussong, Stacy A. Hart, Matthew J. Javors, Martin Shih, Yen-Yu Ian Muir, Eric Fonseca, Rene Solano Strong, Randy Richardson, Arlan G. Lechleiter, James D. Fox, Peter T. Galvan, Veronica TI Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE age-associated; Alzheimer's disease; cerebral amyloid angiopathy; nitric oxide synthase; rapamycin; target-of-rapamycin (TOR); vascular dysfunction ID CEREBRAL AMYLOID ANGIOPATHY; GENETICALLY HETEROGENEOUS MICE; SIROLIMUS-ELUTING STENTS; EXTENDS LIFE-SPAN; TRANSGENIC MICE; MAMMALIAN TARGET; COGNITIVE DEFICITS; PLAQUE-FORMATION; BETA CLEARANCE; MOUSE MODEL AB Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h) APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias. C1 [Lin, Ai-Ling; Muir, Eric; Fox, Peter T.] Res Imaging Inst, San Antonio, TX USA. [Zheng, Wei; Richardson, Arlan G.; Lechleiter, James D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Halloran, Jonathan J.; Burbank, Raquel R.; Hussong, Stacy A.; Fonseca, Rene Solano; Galvan, Veronica] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Halloran, Jonathan J.; Burbank, Raquel R.; Hussong, Stacy A.; Hart, Matthew J.; Fonseca, Rene Solano; Strong, Randy; Richardson, Arlan G.; Galvan, Veronica] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Hart, Matthew J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78245 USA. [Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78245 USA. [Shih, Yen-Yu Ian] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Shih, Yen-Yu Ian] Univ N Carolina, Biomed Res Imaging Ctr, Chapel Hill, NC USA. [Strong, Randy; Richardson, Arlan G.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Strong, Randy; Richardson, Arlan G.] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78245 USA. RP Galvan, V (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM galvanv@uthscsa.edu RI Fox, Peter/B-4725-2010; OI Fox, Peter/0000-0002-0465-2028; Shih, Yen-Yu Ian/0000-0001-6529-911X FU Ellison Medical Foundation; William & Ella Owens Medical Research Foundation; UTHSCSA University Research Council; UTHSCSA Institute for Integration of Medicine and Science; NIA Interventions Testing Center [U01AG022307]; NIH [RC2AG036613]; NIA [5T32AG021890]; UTHSCSA; CTRC at UTHSCSA [NIH-NCI P30 CA54174]; San Antonio Nathan Shock Aging Center [P30AG-13319]; Neurodegeneration Research Center (REAP) from the Research and Development Service of the Department of Veterans Affairs FX This work was supported by an Ellison Medical Foundation New Scholar Award in Aging, a William & Ella Owens Medical Research Foundation Grant and a UTHSCSA University Research Council Award to VG, an UTHSCSA Institute for Integration of Medicine and Science Award to ALL, the NIA Interventions Testing Center (U01AG022307) to RS, RC2AG036613 NIH Recovery Act Grand Opportunities "GO'' grant to AR, and by 5T32AG021890 NIA Biology of Aging Training Grant Fellowship to SH. Images were generated in the Core Optical Imaging Facility, which is supported by UTHSCSA and NIH-NCI P30 CA54174 (CTRC at UTHSCSA). We recognize the support of the San Antonio Nathan Shock Aging Center (P30AG-13319, AR) and the VA Neurodegeneration Research Center (REAP) from the Research and Development Service of the Department of Veterans Affairs to AR and RS. NR 68 TC 42 Z9 43 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2013 VL 33 IS 9 BP 1412 EP 1421 DI 10.1038/jcbfm.2013.82 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 214IQ UT WOS:000324126400013 PM 23801246 ER PT J AU Pu, HJ Guo, YL Zhang, WT Huang, LT Wang, GH Liou, AK Zhang, J Zhang, PY Leak, RK Wang, Y Chen, J Gao, YQ AF Pu, Hongjian Guo, Yanling Zhang, Wenting Huang, Lanting Wang, Guohua Liou, Anthony K. Zhang, Jia Zhang, Pengyue Leak, Rehana K. Wang, Yun Chen, Jun Gao, Yanqin TI Omega-3 polyunsaturated fatty acid supplementation improves neurologic recovery and attenuates white matter injury after experimental traumatic brain injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE behavior (rodent); brain trauma; inflammation; neurodegeneration; white matter/oligodendrocytes ID SPINAL-CORD-INJURY; DOCOSAHEXAENOIC ACID; PARKINSONS-DISEASE; MODEL; RAT; OMEGA-3-FATTY-ACIDS; EXCITOTOXICITY; MECHANISMS; GLUTAMATE; VULNERABILITY AB Dietary supplementation with omega-3 (omega-3) fatty acids is a safe, economical mean of preventive medicine that has shown protection against several neurologic disorders. The present study tested the hypothesis that this method is protective against controlled cortical impact (CCI). Indeed, mice fed with omega-3 polyunsaturated fatty acid (PUFA)-enriched diet for 2 months exhibited attenuated short and long-term behavioral deficits due to CCI. Although omega-3 PUFAs did not decrease cortical lesion volume, these fatty acids did protect against hippocampal neuronal loss after CCI and reduced pro-inflammatory response. Interestingly, omega-3 PUFAs prevented the loss of myelin basic protein (MPB), preserved the integrity of the myelin sheath, and maintained the nerve fiber conductivity in the CCI model. omega-3 PUFAs also directly protected oligodendrocyte cultures from excitotoxicity and blunted the microglial activation-induced death of oligodendrocytes in microglia/oligodendrocyte cocultures. In sum, omega-3 PUFAs elicit multifaceted protection against behavioral dysfunction, hippocampal neuronal loss, inflammation, and loss of myelination and impulse conductivity. The present report is the first demonstration that omega-3 PUFAs protect against white matter injury in vivo and in vitro. The protective impact of omega-3 PUFAs supports the clinical use of this dietary supplement as a prophylaxis against traumatic brain injury and other nervous system disorders. C1 [Pu, Hongjian; Guo, Yanling; Zhang, Wenting; Huang, Lanting; Wang, Guohua; Zhang, Jia; Zhang, Pengyue; Wang, Yun; Chen, Jun; Gao, Yanqin] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. [Pu, Hongjian; Guo, Yanling; Zhang, Wenting; Huang, Lanting; Wang, Guohua; Zhang, Jia; Zhang, Pengyue; Wang, Yun; Chen, Jun; Gao, Yanqin] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Liou, Anthony K.; Chen, Jun; Gao, Yanqin] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Liou, Anthony K.; Chen, Jun; Gao, Yanqin] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA USA. [Liou, Anthony K.; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. RP Gao, YQ (reprint author), Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. EM chenj2@upmc.edu; yqgao@shmu.edu.cn RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU Chinese Ministry of Science and Technology; National Institutes of Health/NINDS [NS36736, NS43802, NS45048, NS056118]; Chinese Natural Science Foundation [30870794, 81020108021, 81171149, 81150110494, 81000497]; VA Research Career Scientist Award; VA Merit Review grant; UPMC FX This research is supported in part by the Special Research Funds from Chinese Ministry of Science and Technology to State Key laboratories (to YG and JC), National Institutes of Health/NINDS grants NS36736, NS43802, NS45048 and NS056118 (to JC), and Chinese Natural Science Foundation grants No 30870794, No 81020108021, No 81171149, No 81150110494, and No 81000497 (to YG). JC is a recipient of the VA Research Career Scientist Award, VA Merit Review grant, and the RK Mellon Endowed Chair from UPMC. NR 40 TC 25 Z9 26 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2013 VL 33 IS 9 BP 1474 EP 1484 DI 10.1038/jcbfm.2013.108 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 214IQ UT WOS:000324126400020 PM 23801244 ER PT J AU Bredella, MA Gerweck, AV Lin, E Landa, MG Torriani, M Schoenfeld, DA Hemphill, LC Miller, KK AF Bredella, Miriam A. Gerweck, Anu V. Lin, Eleanor Landa, Melissa G. Torriani, Martin Schoenfeld, David A. Hemphill, Linda C. Miller, Karen K. TI Effects of GH on Body Composition and Cardiovascular Risk Markers in Young Men With Abdominal Obesity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE DEFICIENCY; PLACEBO-CONTROLLED TRIAL; FATTY LIVER-DISEASE; MITOCHONDRIAL-FUNCTION; INSULIN SENSITIVITY; PHYSICAL-ACTIVITY; VISCERAL FAT; WOMEN; ADULTS; ADIPOSITY AB Context: Visceral adiposity is associated with increased cardiometabolic risk and decreased GH secretion. Objective: Our objective was to determine the effects of GH administration in abdominally obese young men on body composition, including liver fat, mitochondrial function, and cardiovascular (CV) risk markers. Design and Participants: This was a 6-month, randomized, double-blind, placebo-controlled study with 62 abdominally obese men (IGF-1 below the mean, no exclusion based on GH level), 21 to 45 years of age. Main Outcome Measures: We evaluated abdominal fat depots, thigh muscle and fat (computed tomography), fat and lean mass (dual-energy x-ray absorptiometry), intramyocellular and intrahepatic lipids (proton magnetic resonance spectroscopy), mitochondrial function (dynamic phosphorous magnetic resonance spectroscopy), CV risk markers, carotid intimal-medial thickness, and endothelial function. Results: GH administration resulted in a mean IGF-1 SD score increase from -1.9 +/- 0.08 to -0.2 +/- 0.3 in the GH group and a decrease in visceral adipose tissue (VAT), VAT/sc adipose tissue, trunk/extremity fat, intrahepatic lipids, high-sensitivity C-reactive protein and apolipoprotein B/low-density lipoprotein vs placebo after controlling for the increase in weight observed in both groups. There were inverse associations between change in IGF-1 levels and change in VAT, VAT/sc adipose tissue, trunk fat, trunk/extremity fat, high-sensitivity C-reactive protein, and apolipoprotein B. Mitochondrial function improved in the GH group compared with placebo after controlling for change in glucose. There was no change in thigh fat, muscle mass, intramyocellular lipids, cholesterol, fibrinogen, intimal-medial thickness, or endothelial function. There was no increase in fasting glucose or hemoglobin A1c in the GH vs placebo group, although glucose during the 2-hour oral glucose tolerance test increased slightly. Conclusion: GH replacement in abdominally obese men improves body composition, including liver fat, mitochondrial function, and markers of CV risk. Although fasting glucose was unchanged, a slight increase in 2-hour glucose during an oral glucose tolerance test was noted. C1 [Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gerweck, Anu V.; Lin, Eleanor; Landa, Melissa G.; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Hemphill, Linda C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org FU National Institutes of Health [R01 HL-077674, K24 HL092902-03, UL1 RR025758, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants R01 HL-077674, K24 HL092902-03, UL1 RR025758, and K23 RR-23090. Study medication (GH and placebo) only was provided by Genentech, Inc, South San Francisco, California. NR 40 TC 14 Z9 15 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2013 VL 98 IS 9 BP 3864 EP 3872 DI 10.1210/jc.2013-2063 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214YJ UT WOS:000324175200060 PM 23824419 ER PT J AU Kasippillai, T MacArthur, DG Kirby, A Thomas, B Lambalk, CB Daly, MJ Welt, CK AF Kasippillai, Thushiga MacArthur, Daniel G. Kirby, Andrew Thomas, Brett Lambalk, Cornelius B. Daly, Mark J. Welt, Corrine K. TI Mutations in eIF4ENIF1 Are Associated With Primary Ovarian Insufficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INITIATION-FACTOR 4E; DNA-SEQUENCING DATA; SHUTTLING PROTEIN; DROSOPHILA; EIF4E-TRANSPORTER; TRANSFORMATION; TRANSLATION; FRAMEWORK; INTERACTS; NONSENSE AB Context: Primary ovarian insufficiency (POI), or premature ovarian failure, results from ovarian follicle depletion with a consequent elevation of FSH levels before age 40 years. We identified a family in which 9 women in 3 consecutive generations developed menopause at approximately age 30 years. We hypothesized a genetic cause with a dominant mode of inheritance. Design: This was a family-based genetic study and a replicate group of women with POI. Setting: The study was conducted at an academic medical center. Patients: Seven affected women and an obligate carrier and 7 unaffected family members were genotyped. The genes of interest were also sequenced in 38 unrelated women with POI. Intervention: The DNA from 7 family members was subjected to whole-exome sequencing. The genotypes of interest were confirmed and genotypes of additional family members and unrelated women with POI were determined using Sanger sequencing. Main Outcome Measure: A high-impact, deleterious variant that segregated appropriately with POI in the family was required. Results: A heterozygous stop codon (Ser429X) was identified in the eukaryotic translation initiation factor 4E nuclear import factor 1 (eIF4ENIF1) in the proband and all affected women but not in the unaffected family members. The chance that such a high-impact, deleterious variant would segregate appropriately among the affected and unaffected relatives by chance is very low (P < .05). There were no additional mutations identified in eIF4ENIF1 or eIF4E in 38 unrelated women with POI. Conclusion: Data demonstrate a new gene associated with dominantly inherited POI. These results highlight the importance of translation initiation factors and their regulators in ovarian function. C1 [Kasippillai, Thushiga; Welt, Corrine K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [MacArthur, Daniel G.; Kirby, Andrew; Thomas, Brett; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Kasippillai, Thushiga; Lambalk, Cornelius B.] Vrije Univ Med Ctr, Dept Obstet & Gynecol, Div Reprod Med, NL-1007 MB Amsterdam, Netherlands. [MacArthur, Daniel G.; Daly, Mark J.; Welt, Corrine K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [MacArthur, Daniel G.; Daly, Mark J.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU Harvard Clinical and Translational Science Center [1 UL1 RR025758-01] FX This work was supported by the Harvard Clinical and Translational Science Center Grant 1 UL1 RR025758-01. NR 21 TC 13 Z9 14 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2013 VL 98 IS 9 BP E1534 EP E1539 DI 10.1210/jc.2013-1102 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214YJ UT WOS:000324175200013 PM 23902945 ER PT J AU Richard, N Molin, A Coudray, N Rault-Guillaume, P Juppner, H Kottler, ML AF Richard, Nicolas Molin, Arnaud Coudray, Nadia Rault-Guillaume, Pauline Jueppner, Harald Kottler, Marie-Laure TI Paternal GNAS Mutations Lead to Severe Intrauterine Growth Retardation (IUGR) and Provide Evidence for a Role of XL alpha s in Fetal Development SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROGRESSIVE OSSEOUS HETEROPLASIA; PSEUDOHYPOPARATHYROIDISM TYPE 1A; INACTIVATING MUTATIONS; RESISTANCE; GENE; DIFFERENTIATION; G-ALPHA(S); RESTRICTION; EXPRESSION; G(S)ALPHA AB Context: Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia (POH) when paternally inherited. Recent studies have suggested that mutations on the paternal, but not the maternal, GNAS allele could be associated with intrauterine growth retardation (IUGR) and thus small size for gestational age. Objectives: The aim of the study was to confirm and expand these findings in a large number of patients presenting with either PHP-Ia or PPHP/POH. Patients and Methods: We collected birth parameters (ie, gestational age, weight, length, and head circumference) of patients with either PHP-Ia (n = 29) or PPHP/POH (n = 26) with verified GNAS mutations. The parental allele carrying the mutation was assessed by investigating the parents or, when a de novo mutation was identified, through informative intragenic polymorphisms. Results: Heterozygous GNAS mutations on either parental allele were associated with IUGR. However, when these mutations are located on the paternal GNAS allele, IUGR was considerably more pronounced than with mutations on the maternal allele. Moreover, birth weights were lower with paternal GNAS mutations affecting exons 2-13 than with exon 1/intron 1 mutations. Conclusions: These data indicate that a paternally derived GNAS transcript, possibly XL alpha s, is required for normal fetal growth and development and that this transcript affects placental functions. Thus, similar to other imprinted genes, GNAS controls growth and/or fetal development. C1 [Richard, Nicolas; Molin, Arnaud; Coudray, Nadia; Rault-Guillaume, Pauline; Kottler, Marie-Laure] Ctr Hosp Univ Caen, Dept Genet, Reference Ctr Rare Disorders Calcium & Phosphorus, F-14000 Caen, France. [Kottler, Marie-Laure] Univ Caen Basse Normandie, COMETE, F-14032 Caen, France. [Kottler, Marie-Laure] INSERM, U1075, COMETE, F-14032 Caen, France. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kottler, ML (reprint author), Ctr Hosp Univ Hop Clemenceau, Serv Genet, F-14033 Caen, France. EM kottler-ml@chu-caen.fr FU Clinical Research direction of Caen [PHRC 05/011]; National Institutes of Health [R01DK46718-20] FX This work was supported by a grant from the Clinical Research direction of Caen (to M.-L. K.) (PHRC 05/011) and in part by a grant from the National Institutes of Health (R01DK46718-20; to H.J.). NR 30 TC 15 Z9 15 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2013 VL 98 IS 9 BP E1549 EP E1556 DI 10.1210/jc.2013-1667 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214YJ UT WOS:000324175200015 PM 23884777 ER PT J AU Sacks, HS Fain, JN Bahouth, SW Ojha, S Frontini, A Budge, H Cinti, S Symonds, ME AF Sacks, Harold S. Fain, John N. Bahouth, Suleiman W. Ojha, Shalini Frontini, Andrea Budge, Helen Cinti, Saverio Symonds, Michael E. TI Adult Epicardial Fat Exhibits Beige Features SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BROWN ADIPOSE-TISSUE; WHITE ADIPOCYTES; COLD-EXPOSURE; PPAR-GAMMA; OBESITY; EXPRESSION; DISTINCT; HUMANS; MOUSE; IDENTIFICATION AB Context: Human epicardial fat has been designated previously as brown-like fat. The supraclavicular fat depot in man has been defined as beige coexistent with classical brown based on its gene expression profile. Objective: The aim of the study was to establish the gene expression profile and morphology of human epicardial and visceral paracardial fat compared with sc fat. Setting: The study was conducted at a tertiary care hospital cardiac center. Patients: Epicardial, visceral paracardial, and sc fat samples had been taken from middle-aged patients with severe coronary atherosclerosis or valvular heart disease. Interventions: Gene expression was determined by reverse transcription-quantitative PCR and relative abundance of the mitochondrial uncoupling protein-1 (UCP-1) by Western blotting. Epicardial tissue sections from patients were examined by light microscopy, UCP-1 immunohistochemistry, and cell morphometry. Main Outcome Measures: We hypothesized that epicardial fat has a mixed phenotype with a gene expression profile similar to that described for beige cell lineage. Results: Immunoreactive UCP-1 was clearly measurable in each epicardial sample analyzed but was undetectable in each of the 4 other visceral and sc depots. Epicardial fat exhibited high expression of genes for UCP-1, PRDM16, PGC-1 alpha, PPAR gamma, and the beige adipocyte-specific marker CD137, which were also expressed in visceral paracardial fat but only weakly in sternal, upper abdominal, and lower extremity sc fat. Histology of epicardial fat showed small unilocular adipocytes without UCP-1 immunostaining. Conclusion: UCP-1 is relatively abundant in epicardial fat, and this depot possesses molecular features characteristic of those found in vitro in beige lineage adipocytes. C1 [Sacks, Harold S.] VA Greater Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. [Sacks, Harold S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Fain, John N.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA. [Bahouth, Suleiman W.] Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Pharmacol, Memphis, TN 38163 USA. [Ojha, Shalini; Budge, Helen; Symonds, Michael E.] Univ Nottingham Hosp, Sch Clin Sci, Acad Div Child Hlth, Early Life Nutr Res Unit, Nottingham NG7 2UH, England. [Frontini, Andrea; Cinti, Saverio] Univ Ancona, United Hosp, Politecn Marche,Obes Ctr, Dept Expt & Clin Med, I-60020 Ancona, Italy. RP Sacks, HS (reprint author), VA Greater Angeles Healthcare Syst, Endocrinol & Diabet Div 111D,11310 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hsacks@hotmail.com OI Ojha, Shalini/0000-0001-5668-4227; Symonds, Michael/0000-0001-9649-8963 FU European Union FP7 Project DIABAT [HEALTH F2-2011-278373]; Cardiometabolic Disease Research Foundation, Los Angeles, California FX This work was supported by European Union FP7 Project DIABAT (HEALTH F2-2011-278373) (to S.C.), and the Cardiometabolic Disease Research Foundation, Los Angeles, California (to H.S.). NR 41 TC 29 Z9 33 U1 2 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2013 VL 98 IS 9 BP E1448 EP E1455 DI 10.1210/jc.2013-1265 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214YJ UT WOS:000324175200002 PM 23824424 ER PT J AU Del Rossi, G Rechtine, GR Conrad, BP Horodyski, M AF Del Rossi, Gianluca Rechtine, Glenn R. Conrad, Bryan P. Horodyski, MaryBeth TI IS SUB-OCCIPITAL PADDING NECESSARY TO MAINTAIN OPTIMAL ALIGNMENT OF THE UNSTABLE SPINE IN THE PREHOSPITAL SETTING? A PRELIMINARY REPORT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE prehospital care; spinal immobilization; cervical spine ID CERVICAL-SPINE; ANKYLOSING-SPONDYLITIS; IMMOBILIZATION; POSITION; INTACT; INJURY; MODEL AB Background: As prehospital emergency rescuers prepare cervical spine-injured adult patients for immobilization and transport to hospital, it is essential that patients be placed in a favorable position. Previously, it was recommended that patients with cervical spine injuries be immobilized in a slightly flexed position using pads placed beneath the head. However, it is unknown how neck flexion created with pad placement affects the unstable spine. Objective: To determine the effects of three different head positions on the alignment of unstable vertebral segments. Methods: Five cadavers with a complete segmental instability at the C5 and C6 level were included in the study. The head was either placed directly on the ground (or spine board) or on foam pads. Three conditions were tested: no pad; pads 2.84 cm thick; and pads 4.26 cm thick. Pads were positioned beneath the head to determine their effect on spinal alignment. Anterior-posterior translation, flexion-extension motion, and axial displacement across the unstable segment were compared between conditions. Results: Although statistical tests failed to identify any significant differences between pad conditions, some meaningful results were noted. In general, the "no pad" condition aligned the spine in a position that best replicated the intact spine. Conclusions: Because the goal of emergency rescuers is to conserve whatever physiologic or structural integrity of the spinal cord and spinal column that remains, the outcome of this study suggests that this goal may be best achieved using the "no pad" condition. However, it is recommended that more research be conducted to confirm these preliminary findings. (C) 2013 Elsevier Inc. C1 [Del Rossi, Gianluca] Univ S Florida, Dept Orthopaed & Sports Med, Tampa, FL 33612 USA. [Rechtine, Glenn R.] US Dept Vet Affairs, St Petersburg, FL USA. [Conrad, Bryan P.; Horodyski, MaryBeth] Univ Florida, Dept Orthopaed & Rehabil, Gainesville, FL USA. RP Del Rossi, G (reprint author), Univ S Florida, Dept Orthopaed & Sports Med, 13220 USF Laurel Dr,MDF 5111,Mail Code MDC106, Tampa, FL 33612 USA. NR 16 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2013 VL 45 IS 3 BP 366 EP 370 DI 10.1016/j.jemermed.2013.01.042 PG 5 WC Emergency Medicine SC Emergency Medicine GA 213IC UT WOS:000324048400022 PM 23849357 ER PT J AU Mejaddam, AY Elmer, J Sideris, AC Chang, YC Petrovick, L Alam, HB Fagenholz, PJ AF Mejaddam, Ali Y. Elmer, Jonathan Sideris, Antonios C. Chang, Yuchiao Petrovick, Laurie Alam, Hasan B. Fagenholz, Peter J. TI PROLONGED EMERGENCY DEPARTMENT LENGTH OF STAY IS NOT ASSOCIATED WITH WORSE OUTCOMES IN TRAUMATIC BRAIN INJURY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE traumatic brain injury; Emergency Department; length of stay; Glasgow Outcome Scale; mortality ID CRITICALLY-ILL PATIENTS; MYOCARDIAL-INFARCTION; HOSPITAL MORTALITY; DELAYED TRANSFER; UNITED-STATES; QUALITY; IMPACT; CARE; INDICATORS; PROGNOSIS AB Background: Data suggest that prolonged Emergency Department length of stay (EDLOS) has a detrimental effect on outcomes in some critically ill patients. However, the relationship between EDLOS and outcomes in traumatic brain injury (TBI) has not been examined. Objective: Our objective was to determine the effect of EDLOS on neurologic outcomes in TBI patients. Methods: We performed a retrospective analysis of a prospectively identified cohort of patients with moderate (Glasgow Coma Scale [GCS] score 9-13) and severe (GCS <= 8) TBI who presented to a Level 1 trauma center (2006-2010). Inclusion criteria were transfer to the intensive care unit (ICU) or operating room(OR) from the ED. Primary outcome was Glasgow Outcome Scale (GOS) score, a measure of neurologic function, at discharge. We used a proportional odds model to control for significant predictors of GOS in univariate analysis. Results: Two hundred and twenty-four patients were included in the analysis, 77 (34%) of which were transferred to the OR. Median EDLOS was 3.3 h and 81.2% of patients had a GOS score <= 3 (e.g., severe disability, vegetative, or deceased). In multivariable analyses, EDLOS was not associated with GOS score in either ICU bound (p = 0.57) or OR bound (p = 0.11) patients. Younger age, pupil reactivity, and absence of intubation were independent predictors of good outcomes in the ICU group. In OR patients, predictors of higher GOS score included presence of an epidural hemorrhage, absence of midline shift, and pupil reactivity. Conclusions: Our study demonstrates that EDLOS was not associated with poor outcomes in patients with moderate to severe TBI who required intensive care or early operative intervention in an academic Level 1 trauma center. (C) 2013 Elsevier Inc. C1 [Mejaddam, Ali Y.; Sideris, Antonios C.; Chang, Yuchiao; Petrovick, Laurie; Alam, Hasan B.; Fagenholz, Peter J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Elmer, Jonathan] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Elmer, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2013 VL 45 IS 3 BP 384 EP 390 DI 10.1016/j.jemermed.2013.04.015 PG 7 WC Emergency Medicine SC Emergency Medicine GA 213IC UT WOS:000324048400025 PM 23769388 ER PT J AU Renouf, DJ Zhai, RH Sun, B Xu, W Cheung, WY Heist, RS Kulke, MH Cescon, D Asomaning, K Marshall, AL Li, S Christiani, DC Liu, G AF Renouf, Daniel J. Zhai, Rihong Sun, Bin Xu, Wei Cheung, Winson Y. Heist, Rebecca S. Kulke, Matthew H. Cescon, David Asomaning, Kofi Marshall, Ariella L. Li, Su Christiani, David C. Liu, Geoffrey TI Association of MDM2 T309G and p53 Arg72Pro polymorphisms and gastroesophageal reflux disease with survival in esophageal adenocarcinoma SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE esophageal cancer; GERD; MDM2; p53; polymorphisms ID SINGLE NUCLEOTIDE POLYMORPHISM; MDM2 PROMOTER POLYMORPHISM; CELL LUNG-CANCER; BARRETTS-ESOPHAGUS; GASTRIC-CARCINOMA; IN-VITRO; P53; RISK; PROGNOSIS; POPULATION AB Background and Aim: Although gastroesophageal reflux disease (GERD) is a risk factor for esophageal adenocarcinoma (EAC), some patients develop EAC in the absence of GERD. A putative mechanism of reflux-induced tumorigenesis involves disruptions in the p53 pathway. We assessed the interaction of GERD and p53 pathway polymorphisms on EAC prognosis. Methods: In a prospective cohort of 358 EAC patients, clinical data (including GERD history and survival) were collected. Germline DNA was genotyped for MDM2 T309G and p53 Arg72Pro. Cox proportional hazards models were used to determine adjusted hazard ratios (AHR) for associations between genotype, GERD, and genotype-GERD interactions with survival. Results: Compared with other genotypes, MDM2 G/G (median overall survival 21 vs 30 months; P < 0.001) and p53 Pro/Pro (12 vs 30 months; P = 0.004) were associated with shorter survival. When analyzed by GERD, MDM2 G/G was associated with shorter survival in patients without GERD (AHR 3.4, 95% CI 2.0-6.0), but not in patients with GERD (AHR 1.1 [0.7-1.8]); the MDM2-GERD interaction was significant (P = 0.003). A similar trend was seen for p53 Pro/Pro (AHRs 2.5 without GERD vs 1.4 with GERD). Combined analysis of at-risk variants (MDM2 G or p53 Pro), revealed each additional at-risk variant was associated with shorter survival in patients without GERD (AHR 1.6) but not with GERD (AHR 1.0). Conclusions: MDM2 G/G and the combination of MDM2 G and p53 Pro were negative prognostic factors for EAC patients without GERD but not for those with GERD. There may be biological differences between GERD positive and GERD negative EAC. C1 [Renouf, Daniel J.; Cescon, David; Liu, Geoffrey] Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. [Sun, Bin; Xu, Wei] Princess Margaret Hosp, Dept Biostat, Toronto, ON M4X 1K9, Canada. [Xu, Wei; Liu, Geoffrey] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. [Renouf, Daniel J.; Cheung, Winson Y.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Zhai, Rihong; Asomaning, Kofi; Marshall, Ariella L.; Li, Su; Christiani, David C.; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Heist, Rebecca S.; Christiani, David C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Renouf, DJ (reprint author), British Columbia Canc Agcy, 600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM drenouf@bccancer.bc.ca RI Liu, Geoffrey/N-4421-2016 FU Alan Brown Chair (in Molecular Genomics); Cancer Care Ontario Chair in Experimental Therapeutics and Population Studies; Posluns Family Fund FX Funding for this study was provided by the Alan Brown Chair (in Molecular Genomics (GL), Cancer Care Ontario Chair in Experimental Therapeutics and Population Studies (GL), and the Posluns Family Fund. NR 34 TC 6 Z9 6 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD SEP PY 2013 VL 28 IS 9 BP 1482 EP 1488 DI 10.1111/jgh.12286 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 204SP UT WOS:000323389700011 PM 23735059 ER PT J AU Gradl, G Neuhaus, V Fuchsberger, T Guitton, TG Prommersberger, KJ Ring, D AF Gradl, Gertraud Neuhaus, Valentin Fuchsberger, Thomas Guitton, Thierry G. Prommersberger, Karl-Josef Ring, David CA Sci Variation Grp TI Radiographic Diagnosis of Scapholunate Dissociation Among Intra-articular Fractures of the Distal Radius: Interobserver Reliability SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Interobserver reliability; distal radius intra-articular fracture; scapholunate injury ID COMPUTED-TOMOGRAPHY; LIGAMENT INJURIES; CT ARTHROGRAPHY; WRIST; INSTABILITY AB Purpose To evaluate the reliability and accuracy of diagnosis of scapholunate dissociation (SLD) among AO type C (compression articular) fractures of the distal radius. Methods A total of 217 surgeons evaluated 21 sets of radiographs with type C fractures of the distal radius for which the status of the scapholunate interosseous ligament was established by preoperative 3-compartment computed tomographic arthrography with direct operative visualization of diagnosed SLD (reference standard). Observers were asked whether SLD was present, and if yes, whether they would recommend operative treatment. Diagnostic performance characteristics were calculated with respect to the reference standard. We assessed interobserver reliability using the Fleiss generalized kappa. Results The interobserver agreement for radiographic diagnosis of SLD was moderate (kappa = 0.44). Correct diagnosis for a given set of radiographs ranged from 8% to 98% (average, 79%) of observers. Diagnostic performance characteristics were: 69% sensitivity, 84% specificity, 84% accuracy, 68% positive predictive value, and 84% negative predictive value. Based on a prevalence of 5%, Bayes adjusted positive and negative predictive values were 18% and 98%, respectively. Raters recommended operative treatment in 74% to 100% of patients diagnosed with SLD. Conclusions Radiographs are moderately reliable and are better at ruling out than ruling in SLD associated with type C fracture of the distal radius. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved. Type of study/level of evidence Diagnostic III. C1 Univ Aachen, Med Ctr, Dept Trauma & Reconstruct Surg, Aachen, Germany. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Rhon Klinikum AG, Klin Handchirurg, Bad Neustadt an der Saale, Germany. Acad Med Ctr Amsterdam, Dept Orthopaed Surg, Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@partners.org RI Page, Richard/K-6327-2015; Fernandes, C/F-9839-2012; OI Page, Richard/0000-0002-2225-7144; Fernandes, C/0000-0003-0146-6091; Streubel, Philipp/0000-0002-4585-1779; Guitton, Thierry/0000-0002-2599-1985; Soong, Maximillian/0000-0003-0333-8181; adolfsson, lars/0000-0001-7873-3093; Beeres, Frank/0000-0002-7277-3438; Neuhaus, Valentin/0000-0003-4012-5628 NR 19 TC 10 Z9 10 U1 1 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2013 VL 38A IS 9 BP 1685 EP 1690 DI 10.1016/j.jhsa.2013.05.039 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 214QD UT WOS:000324149500003 PM 23910379 ER PT J AU Douglas, VC Hessler, CS Dhaliwal, G Betjemann, JP Fukuda, KA Alameddine, LR Lucatorto, R Johnston, SC Josephson, SA AF Douglas, Vanja C. Hessler, Christine S. Dhaliwal, Gurpreet Betjemann, John P. Fukuda, Keiko A. Alameddine, Lama R. Lucatorto, Rachael Johnston, S. Claiborne Josephson, S. Andrew TI The AWOL tool: Derivation and validation of a delirium prediction rule SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID INTENSIVE-CARE PATIENTS; OLDER PATIENTS; MEDICAL INPATIENTS; CLINICAL JUDGMENT; MINI-COG; OUTCOMES; MODEL; SURGERY; DEMENTIA; ILLNESS AB BACKGROUND: Risk factors for delirium are well-described, yet there is no widely used tool to predict the development of delirium upon admission in hospitalized medical patients. OBJECTIVE: To develop and validate a tool to predict the likelihood of developing delirium during hospitalization. DESIGN: Prospective cohort study with derivation (May 2010-November 2010) and validation (October 2011-March 2012) cohorts. SETTING: Two academic medical centers and 1 Veterans Affairs medical center. PATIENTS: Consecutive medical inpatients (209 in the derivation and 165 in the validation cohort) over age 50 years without delirium at the time of admission. MEASUREMENTS: Delirium assessed daily for up to 6 days using the Confusion Assessment Method. RESULTS: The AWOL prediction rule was derived by assigning 1 point to each of 4 items assessed upon enrollment that were independently associated with the development of delirium (Age80 years, failure to spell World backward, disOrientation to place, and higher nurse-rated iLlness severity). Higher scores were associated with higher rates of delirium in the derivation and validation cohorts (P for trend<0.001 and 0.025, respectively). Rates of delirium according to score in the combined population were: 0(1/50, 2%), 1(5/141, 4%), 2(15/107, 14%), 3(10/50, 20%), and 4(7/11, 64%) (P for trend<0.001). Area under the receiver operating characteristic curve for the derivation and validation cohorts was 0.81 (0.73-0.90) and 0.69 (0.54-0.83) respectively. CONCLUSIONS: The AWOL prediction rule characterizes medical patients' risk for delirium at the time of hospital admission and could be used for clinical stratification and in trials of delirium prevention. Journal of Hospital Medicine 2013;8:493-499. (c) 2013 Society of Hospital Medicine C1 [Douglas, Vanja C.; Hessler, Christine S.; Betjemann, John P.; Fukuda, Keiko A.; Alameddine, Lama R.; Johnston, S. Claiborne; Josephson, S. Andrew] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Dhaliwal, Gurpreet; Lucatorto, Rachael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet; Lucatorto, Rachael] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. [Alameddine, Lama R.] San Francisco VA Med Ctr, Dept Psychol, San Francisco, CA USA. [Johnston, S. Claiborne] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Douglas, VC (reprint author), UCSF Dept Neurol, Parnassus Ave,M798,San Francisco, San Francisco, CA 94143 USA. EM Vanja.Douglas@ucsf.edu FU University of California, San Francisco FX The following University of California, San Francisco neurology residents provided follow-up of study subjects on weekends and were financially compensated: Amar Dhand, MD, DPhil; Tim West, MD; Sarah Shalev, MD; Karen DaSilva, MD; Mark Burish, MD, PhD; Maggie Waung, MD, PhD; Raquel Gardner, MD; Molly Burnett, MD; Adam Ziemann, MD, PhD; Kathryn Kvam, MD; Neel Singhal, MD, PhD; James Orengo, MD, PhD; Kelly Mills, MD; and Joanna Hellmuth, MD, MHS. The authors are grateful to Dr. Douglas Bauer for assisting with the study design. NR 41 TC 6 Z9 7 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2013 VL 8 IS 9 BP 493 EP 499 DI 10.1002/jhm.2062 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 212ZL UT WOS:000324022200003 PM 23922253 ER PT J AU Reddy, AT Lakshmi, SP Dornadula, S Pinni, S Rampa, DR Reddy, RC AF Reddy, Aravind T. Lakshmi, Sowmya P. Dornadula, Sireesh Pinni, Sudheer Rampa, Dileep R. Reddy, Raju C. TI The Nitrated Fatty Acid 10-Nitro-Oleate Attenuates Allergic Airway Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; KAPPA-B KINASE; PPAR-GAMMA; SEVERE ASTHMA; ALVEOLAR MACROPHAGES; MURINE MODEL; HUMAN NEUTROPHILS; INFLAMMATION; CORTICOSTEROIDS; INHIBITION AB Asthma is a serious, growing problem worldwide. Inhaled steroids, the current standard therapy, are not always effective in this chronic inflammatory disease and can cause adverse effects. We tested the hypothesis that nitrated fatty acids (NFAs) may provide an effective alternative treatment. NFAs are endogenously produced by nonenzymatic reaction of NO with unsaturated fatty acids and exert anti-inflammatory actions both by activating the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)gamma and via PPAR-independent mechanisms, but whether they might ameliorate allergic airway disease was previously untested. We found that pulmonary delivery of the NFA 10-nitro-oleic acid (OA-NO2) reduced the severity of murine allergic airway disease, as assessed by various pathological and molecular markers. Fluticasone, an inhaled steroid commonly used to treat asthma, produced similar effects on most end points, but only OA-NO2 induced robust apoptosis of neutrophils and their phagocytosis by alveolar macrophages. This suggests that OA-NO2 may be particularly effective in neutrophil-rich, steroid-resistant severe asthma. In primary human bronchial epithelial cells, OA-NO2 blocked phosphorylation and degradation of I kappa B and enhanced inhibitory binding of PPAR gamma to NF-kappa B. Our results indicate that the NFA OA-NO2 is efficacious in preclinical models of allergic airway disease and may have potential for treating asthma patients. C1 Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Reddy, RC (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. EM reddyrc@upmc.edu FU National Institutes of Health [HL093196] FX This work was supported by National Institutes of Health Grant HL093196 (to R.C.R.). NR 46 TC 16 Z9 16 U1 0 U2 2 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 1 PY 2013 VL 191 IS 5 BP 2053 EP 2063 DI 10.4049/jimmunol.1300730 PG 11 WC Immunology SC Immunology GA 204TU UT WOS:000323393300005 PM 23913958 ER PT J AU Pacheco, Y McLean, AP Rohrbach, J Porichis, F Kaufmann, DE Kavanagh, DG AF Pacheco, Yovana McLean, Anna P. Rohrbach, Janine Porichis, Filippos Kaufmann, Daniel E. Kavanagh, Daniel G. TI Simultaneous TCR and CD244 Signals Induce Dynamic Downmodulation of CD244 on Human Antiviral T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID 2B4 CD244; SURFACE EXPRESSION; INFECTION; EXHAUSTION; LIGAND; ORGANIZATION; THRESHOLDS; ACTIVATION; RECEPTORS; MECHANISM AB Various cosignaling molecules on T cells can contribute to activation, inhibition, or exhaustion, depending on context. The surface receptor signaling lymphocytic activation molecule (SLAM) family receptor CD244 (2B4/SLAMf4) has been shown to be capable of either inhibitory or enhancing effects upon engagement of its ligand CD48 (SLAMf2). We examined phenotypes of CD8 T cells from HIV+ and HIVneg human donors, specific for HIV and/or respiratory syncytial virus. Cultured and ex vivo CD8 T cells expressed PD-1, CD244, and TIM-3. We found that ex vivo CD8 T cells downregulated CD244 in response to superantigen. Furthermore, cognate peptide induced rapid downregulation of both CD244 and TIM-3, but not PD-1, on CD8 T cell clones. CD244 downmodulation required simultaneous signaling via both TCR and CD244 itself. Using a pH-sensitive fluorophore conjugated to avidin-Ab tetramers, we found that CD244 crosslinking in the presence of TCR signaling resulted in rapid transport of CD244 to an acidic intracellular compartment. Downregulation was not induced by PMA-ionomycin, or prevented by PI3K inhibition, implicating a TCR-proximal signaling mechanism. CD244 internalization occurred within hours of TCR stimulation and required less peptide than was required to induce IFN-gamma production. The degree of CD244 internalization varied among cultured CD8 T cell lines of different specificities, and correlated with the enhancement of IFN-gamma production in response to CD48 blockade in HIV+, but not HIVneg, subjects. Our results indicate that rapid CD244 internalization is induced by a two-signal mechanism and plays a role in modulation of antiviral CD8 T cell responses by CD48-CD244 signaling. C1 [Pacheco, Yovana; McLean, Anna P.; Rohrbach, Janine; Porichis, Filippos; Kaufmann, Daniel E.; Kavanagh, Daniel G.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. [Kaufmann, Daniel E.] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ H2X 1P1, Canada. RP Kavanagh, DG (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, 400 Tech Sq, Cambridge, MA 02139 USA. EM dkavanagh@partners.org FU Terry and Susan Ragon Foundation; National Institutes of Health/National Institute of Allergy and Infectious Diseases [1R56AI095088, 5R01AI30914, P01 AI-080192, P30 AI060354]; Research Scholar Career Award of the Quebec Health Research Fund (Fonds de recherche du Quebec-Sante) FX This work was supported by the Terry and Susan Ragon Foundation; National Institutes of Health/National Institute of Allergy and Infectious Diseases Grants 1R56AI095088 and 5R01AI30914 (to D.G.K.), P01 AI-080192 (to D.E.K. and D.G.K.), and P30 AI060354 (Harvard University Center for AIDS Research); and a Research Scholar Career Award of the Quebec Health Research Fund (Fonds de recherche du Quebec-Sante) (to D.E.K.). NR 38 TC 10 Z9 10 U1 0 U2 1 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 1 PY 2013 VL 191 IS 5 BP 2072 EP 2081 DI 10.4049/jimmunol.1300435 PG 10 WC Immunology SC Immunology GA 204TU UT WOS:000323393300007 PM 23913963 ER PT J AU Azzi, J Skartsis, N Mounayar, M Magee, CN Batal, I Ting, C Moore, R Riella, LV Ohori, S Abdoli, R Smith, B Fiorina, P Heathcote, D Bakhos, T Ashton-Rickardt, PG Abdi, R AF Azzi, Jamil Skartsis, Nikolaos Mounayar, Marwan Magee, Ciara N. Batal, Ibrahim Ting, Christopher Moore, Robert Riella, Leonardo V. Ohori, Shunsuke Abdoli, Rozita Smith, Brian Fiorina, Paolo Heathcote, Dean Bakhos, Tannous Ashton-Rickardt, Philip G. Abdi, Reza TI Serine Protease Inhibitor 6 Plays a Critical Role in Protecting Murine Granzyme B-Producing Regulatory T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATED SUPPRESSION; IN-VIVO; DEATH; LUCIFERASE; ALLOGRAFTS; TOLERANCE; REJECTION; RESPONSES; PERFORIN; SURVIVAL AB Regulatory T cells (Tregs) play a pivotal role in the maintenance of immune tolerance and hold great promise as cell therapy for a variety of immune-mediated diseases. However, the cellular mechanisms that regulate Treg maintenance and homeostasis have yet to be fully explored. Although Tregs express granzyme-B (GrB) to suppress effector T cells via direct killing, the mechanisms by which they protect themselves from GrB-mediated self-inflicted damage are unknown. To our knowledge, we show for the first time that both induced Tregs and natural Tregs (nTregs) increase their intracellular expression of GrB and its endogenous inhibitor, serine protease inhibitor 6 (Spi6) upon activation. Subcellular fractionation and measurement of GrB activity in the cytoplasm of Tregs show that activated Spi6(-/-) Tregs had significantly higher cytoplasmic GrB activity. We observed an increase in GrB-mediated apoptosis in Spi6(-/-) nTregs and impaired suppression of alloreactive T cells in vitro. Spi6(-/-) Tregs were rescued from apoptosis by the addition of a GrB inhibitor (Z-AAD-CMK) in vitro. Furthermore, adoptive transfer experiments showed that Spi6(-/-) nTregs were less effective than wild type nTregs in suppressing graft-versus-host disease because of their impaired survival, as shown in our in vivo bioluminescence imaging. Finally, Spi6-deficient recipients rejected MHC class II-mismatch heart allografts at a much faster rate and showed a higher rate of apoptosis among Tregs, as compared with wild type recipients. To our knowledge, our data demonstrate, for the first time, a novel role for Spi6 in Treg homeostasis by protecting activated Tregs from GrB-mediated injury. These data could have significant clinical implications for Treg-based therapy in immune-mediated diseases. C1 [Azzi, Jamil; Skartsis, Nikolaos; Mounayar, Marwan; Magee, Ciara N.; Batal, Ibrahim; Ting, Christopher; Moore, Robert; Riella, Leonardo V.; Ohori, Shunsuke; Abdoli, Rozita; Smith, Brian; Fiorina, Paolo; Abdi, Reza] Brigham & Womens Hosp, Transplantat Res Ctr, Div Renal, Boston, MA 02115 USA. [Azzi, Jamil; Skartsis, Nikolaos; Mounayar, Marwan; Magee, Ciara N.; Batal, Ibrahim; Ting, Christopher; Moore, Robert; Riella, Leonardo V.; Ohori, Shunsuke; Abdoli, Rozita; Smith, Brian; Fiorina, Paolo; Abdi, Reza] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Heathcote, Dean; Ashton-Rickardt, Philip G.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Med, Sect Immunobiol,Div Immunol & Inflammat, London SW7 2AZ, England. [Bakhos, Tannous] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Ctr Neurosci, Mol Neurogenet Unit, Boston, MA 02129 USA. RP Abdi, R (reprint author), Brigham & Womens Hosp, Transplant Res Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [RO1AI091930] FX This work was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award RO1AI091930 (to R. Abdi). NR 30 TC 6 Z9 6 U1 0 U2 2 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 1 PY 2013 VL 191 IS 5 BP 2319 EP 2327 DI 10.4049/jimmunol.1300851 PG 9 WC Immunology SC Immunology GA 204TU UT WOS:000323393300033 PM 23913965 ER PT J AU Becerra, L Navratilova, E Porreca, F Borsook, D AF Becerra, L. Navratilova, E. Porreca, F. Borsook, D. TI Analogous responses in the nucleus accumbens and cingulate cortex to pain onset (aversion) and offset (relief) in rats and humans SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE anterior cingulate cortex; nucleus accumbens; aversion and reward; pain; fMRI ID VON ECONOMO NEURONS; ANTERIOR CINGULATE; BRAIN MECHANISMS; BASAL GANGLIA; DOPAMINE; ACTIVATION; ANALGESIA; PLACEBO; MODULATION; RECEPTORS AB In humans, functional magnetic resonance imaging (fMRI) activity in the anterior cingulate cortex (ACC) and the nucleus accumbens (NAc) appears to reflect affective and motivational aspects of pain. The responses of this reward-aversion circuit to relief of pain, however, have not been investigated in detail. Moreover, it is not clear whether brain processing of the affective qualities of pain in animals parallels the mechanisms observed in humans. In the present study, we analyzed fMRI blood oxygen level-dependent (BOLD) activity separately in response to an onset (aversion) and offset (reward) of a noxious heat stimulus to a dorsal part of a limb in both humans and rats. We show that pain onset results in negative activity change in the NAc and pain offset produces positive activity change in the ACC and NAc. These changes were analogous in humans and rats, suggesting that translational studies of brain circuits modulated by pain are plausible and may offer an opportunity for mechanistic investigation of pain and pain relief. C1 [Becerra, L.] Boston Childrens Hosp, PAIN Grp, Waltham, MA 02453 USA. [Becerra, L.; Borsook, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Porreca, F.] Univ Arizona, Dept Pharmacol, Tucson, AZ USA. RP Becerra, L (reprint author), Boston Childrens Hosp, Ctr Pain & Brain, 9 Hope Ave, Waltham, MA 02453 USA. EM lino.becerra@childrens.harvard.edu FU Herlands Fund for Pain Research; National Institute of Neurological Disorders and Stroke [R01 NS066958] FX This work was supported by the Herlands Fund for Pain Research (to D. Borsook and L. Becerra) and National Institute of Neurological Disorders and Stroke Grant R01 NS066958 (to F. Porreca). NR 69 TC 23 Z9 24 U1 1 U2 14 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2013 VL 110 IS 5 BP 1221 EP 1226 DI 10.1152/jn.00284.2013 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 213YA UT WOS:000324095300016 PM 23785130 ER PT J AU Chen, YCI Cypess, AM Chen, YC Palmer, M Kolodny, G Kahn, CR Kwong, KK AF Chen, Yin-Ching Iris Cypess, Aaron M. Chen, Yih-Chieh Palmer, Matthew Kolodny, Gerald Kahn, C. Ronald Kwong, Kenneth K. TI Measurement of Human Brown Adipose Tissue Volume and Activity Using Anatomic MR Imaging and Functional MR Imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE F-18-FDG; MR imaging; fMRI; cold-activation; brown adipose tissue ID IN-VIVO; FAT; COLD; UCP1; THERMOGENESIS; RESPONSES; MICE AB The aim of this study was to assess the volume and function of human brown adipose tissue (BAT) in vivo using MR imaging. Methods: BAT volumes under thermoneutral conditions in the cervical areas were assessed via water-fat contrast using the Dixon method and via water-saturation efficiency using fast spin-echo and T2-weighted images. The existence of cervical BAT was also assessed by F-18-FDG PET/CT scans in the same subjects. BAT functionality was assessed via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal changes in response to a mild cold challenge. Results: Under thermoneutral conditions, we were able to distinguish BAT from white adipose tissue in the cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and higher water-saturation efficiency in MR imaging scans. The location and volume of BAT assessed by MR imaging were comparable to the measurements by F-18-FDG PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by 10.7% +/- 1.8% (P < 0.01). Conclusion: We demonstrated the feasibility of using MR imaging and fMRI to assess BAT volume and BAT responses to mild cold stimulation in the cervical areas of human subjects. C1 [Chen, Yin-Ching Iris; Kwong, Kenneth K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Chen, Yin-Ching Iris; Cypess, Aaron M.; Chen, Yih-Chieh; Palmer, Matthew; Kolodny, Gerald; Kahn, C. Ronald; Kwong, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA. [Cypess, Aaron M.; Kahn, C. Ronald] Joslin Diabet Ctr, Div Res, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. [Chen, Yih-Chieh; Palmer, Matthew; Kolodny, Gerald] Beth Israel Deaconess Med Ctr, Dept Radiol, Div Nucl Med, Boston, MA 02215 USA. RP Chen, YCI (reprint author), Massachusetts Gen Hosp, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM iris@nmr.mgh.harvard.edu FU NIH [DK087317, DK055545, DK033201, DK081604, DK046200, RR025757, P30 DK036836]; Clinical Translational Science Award from the National Center for Research Resources (NCRR), Harvard Catalyst [UL1RR025758]; BIDMC from the National Center for Research Resources (NCRR), Harvard Catalyst; Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University; Eli Lilly Foundation FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work was supported by NIH grants DK087317, DK055545, DK033201, DK081604, DK046200, RR025757, and P30 DK036836; the Clinical Translational Science Award UL1RR025758 to Harvard University and BIDMC from the National Center for Research Resources (NCRR), Harvard Catalyst; the Harvard Clinical and Translational Science Center (NIH award no. UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers); and the Eli Lilly Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers, NCRR, or NIH. No other potential conflict of interest relevant to this article was reported. NR 20 TC 31 Z9 33 U1 1 U2 6 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP 1 PY 2013 VL 54 IS 9 BP 1584 EP 1587 DI 10.2967/jnumed.112.117275 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 214OM UT WOS:000324143400015 PM 23868958 ER PT J AU McMahan, RD Knight, SJ Fried, TR Sudore, RL AF McMahan, Ryan D. Knight, Sara J. Fried, Terri R. Sudore, Rebecca L. TI Advance Care Planning Beyond Advance Directives: Perspectives From Patients and Surrogates SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Advance directives; decision making; aging; qualitative research ID LIFE DECISION-MAKING; OF-LIFE; MEDICAL-CARE; LIVING WILL; HEALTH; DEATH; PREFERENCES; DISAGREE; FAMILY; OTHERS AB Context. Advance care planning (ACP) has focused on documenting life-sustaining treatment preferences in advance directives (ADs). The ADs alone may be insufficient to prepare diverse patients and surrogates for complex medical decisions. Objectives. To understand what steps best prepare patients and surrogates for decision making. Methods. We conducted 13 English/Spanish focus groups with participants from a Veterans Affairs and county hospital and the community. Seven groups included patients (n = 38), aged >= 65 years, who reported making serious medical decisions. Six separate groups included surrogates (n = 31), aged >= 18 years, who made decisions for others. Semistructured focus groups asked what activities best prepared the participants for decision making. Two investigators independently coded data and performed thematic content analysis. Disputes were resolved by consensus. Results. The mean +/- SD patient age was 78 +/- 8 years, and 61% were nonwhite. The mean +/- SD surrogate age was 57 +/- 10 years, and 91% were nonwhite. Qualitative analysis identified four overarching themes about how to best prepare for decision making: 1) identify values based on past experiences and quality of life, 2) choose surrogates wisely and verify that they understand their role, 3) decide whether to grant leeway in surrogate decision making, and 4) inform other family and friends of one's wishes to prevent conflict. Conclusion. Beyond ADs, patients and surrogates recommend several additional steps to prepare for medical decision making including using past experiences to identify values, verifying that the surrogate understands their role, deciding whether to grant surrogates leeway, and informing other family and friends of one's wishes. Future ACP interventions should consider incorporating these additional ACP activities. Published by Elsevier Inc. on behalf of U. S. Cancer Pain Relief Committee. C1 [McMahan, Ryan D.; Knight, Sara J.; Sudore, Rebecca L.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [McMahan, Ryan D.; Sudore, Rebecca L.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94121 USA. [Knight, Sara J.] Vet Hlth Adm, Hlth Serv Res & Dev Serv, Washington, DC USA. [Fried, Terri R.] Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. [Fried, Terri R.] Yale Univ, Sch Med, New Haven, CT USA. RP Sudore, RL (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM rebecca.sudore@ucsf.edu FU U.S. Department of Veterans Affairs; National Palliative Care Research Center FX This study was supported by the U.S. Department of Veterans Affairs and the National Palliative Care Research Center. The funding sources had no role in the creation of study materials, data collection, analysis, or interpretation of the data. No authors report any conflict of interest. NR 46 TC 23 Z9 23 U1 2 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2013 VL 46 IS 3 BP 355 EP 365 DI 10.1016/j.jpainsymman.2012.09.006 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 213BA UT WOS:000324026700005 PM 23200188 ER PT J AU Vidor, LP Torres, ILS de Souza, ICC Fregni, F Caumo, W AF Vidor, Liliane Pinto Torres, Iraci L. S. Custodio de Souza, Izabel Cristina Fregni, Felipe Caumo, Wolnei TI Analgesic and Sedative Effects of Melatonin in Temporomandibular Disorders: A Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Melatonin; myofascial pain; temporomandibular pain; clinical trial; pain threshold ID CLINICAL-TRIALS; ABDOMINAL HYSTERECTOMY; FIBROMYALGIA SYNDROME; SLEEP DISTURBANCE; OROFACIAL PAIN; CYCLOBENZAPRINE; CORTICOSTERONE; METAANALYSIS; MANAGEMENT; RECEPTORS AB Context. The association between myofascial temporomandibular disorder (TMD) and nonrestorative sleep supports the investigation of therapies that can modulate the sleep/wake cycle. In this context, melatonin becomes an attractive treatment option for myofascial TMD pain. Objectives. To investigate the effects of melatonin on pain (primary aim) and sleep (secondary aim) as compared with placebo in a double-blind, randomized, parallel-group trial. Methods. Thirty-two females, aged 20-40 years, with myofascial TMD pain were randomized into placebo or melatonin (5 mg) treatment groups for a period of four weeks. Results. There was a significant interaction (time vs. group) for the main outcomes of pain scores as indexed by the visual analogue scale and pressure pain threshold (analysis of variance; P < 0.05 for these analyses). Post hoc analysis showed that the treatment reduced pain scores by -44% (95% CI -57%, -26%) compared with placebo, and it also increased the pressure pain threshold by 39% (95% CI 14%, 54%). The use of analgesic doses significantly decreased with time (P < 0.01). The daily analgesic doses decreased by -66% (95% CI -94%, -41%) when comparing the two groups. Additionally, melatonin improved sleep quality, but its effect on pain was independent of the effect on sleep quality. Conclusion. This study provides additional evidence supporting the analgesic effects of melatonin on pain scores and analgesic consumption in patients with mild-to-moderate chronic myofascial TMD pain. Furthermore, melatonin improves sleep quality but its effect on pain appears to be independent of changes in sleep quality. (C) 2013 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Caumo, Wolnei] Hosp Clin Porto Alegre, Pain & Palliat Care Serv, BR-90035003 Porto Alegre, RS, Brazil. [Custodio de Souza, Izabel Cristina; Caumo, Wolnei] Hosp Clin Porto Alegre, Lab Pain & Neuromodulat, BR-90035003 Porto Alegre, RS, Brazil. [Torres, Iraci L. S.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Inst Basic Hlth Sci, Dept Pharmacol, Porto Alegre, RS, Brazil. [Vidor, Liliane Pinto; Torres, Iraci L. S.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Fac Med, Postgrad Program Med Sci, Porto Alegre, RS, Brazil. [Fregni, Felipe] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr,Berenson Allen Ctr, Boston, MA 02115 USA. RP Caumo, W (reprint author), Hosp Clin Porto Alegre, Lab Pain & Neuromodulat, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. EM caumo@cpovo.net RI Torres, iraci/G-6693-2012 OI Torres, iraci/0000-0002-3081-115X FU CNPq; PNPD/CAPES; FAPERGS; CAPES FX The present research was supported by the following Brazilian agencies: CNPq (research grant to Drs. Torres and Caumo) and PNPD/CAPES (postdoctoral grant to Dr. Custodio de Souza). The Hospital de Clinicas de Porto Alegre and the Federal University of Rio Grande do Sul received support from the following Brazilian governmental agencies: FAPERGS, CNPq, and CAPES. The Postgraduate Research Group at the Hospital de Clinicas de Porto Alegre provided medical and administrative support. The authors declare that there are no financial or other relationships that might lead to conflicts of interest. NR 46 TC 11 Z9 11 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2013 VL 46 IS 3 BP 422 EP 432 DI 10.1016/j.jpainsymman.2012.08.019 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 213BA UT WOS:000324026700012 PM 23195393 ER PT J AU Katz, A Hundal, NV Yuan, Q Shreffler, W AF Katz, Aubrey Hundal, Navneet Virk Yuan, Qian Shreffler, Wayne TI Cow's Milk Allergy: A New Approach Needed? SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID PROBIOTIC SUPPLEMENTATION; CHILDREN C1 [Katz, Aubrey; Hundal, Navneet Virk; Yuan, Qian] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Shreffler, Wayne] Massachusetts Gen Hosp, Food Allergy Ctr, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Katz, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Massachusetts Gen Hosp,Food Allergy Ctr, 175 Cambridge St, Boston, MA 02114 USA. EM ajkatz@partners.org NR 10 TC 0 Z9 0 U1 1 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2013 VL 163 IS 3 BP 620 EP 622 DI 10.1016/j.jpeds.2013.05.005 PG 3 WC Pediatrics SC Pediatrics GA 212LQ UT WOS:000323985300003 PM 23809049 ER PT J AU Wilens, TE Rosenbaum, JF AF Wilens, Timothy E. Rosenbaum, Jerrold F. TI Transitional Aged Youth: A New Frontier in Child and Adolescent Psychiatry SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID COMORBIDITY; PREVALENCE; DISORDERS; ONSET; BRAIN C1 [Wilens, Timothy E.; Rosenbaum, Jerrold F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, 55 Parkman St, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [DA016264] NR 10 TC 10 Z9 10 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2013 VL 52 IS 9 BP 887 EP 890 DI 10.1016/j.jaac.2013.04.020 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 212TS UT WOS:000324006300001 PM 23972688 ER PT J AU Quin, JA Hattler, B Bishawi, M Baltz, J Gupta, S Collins, JF Grover, FL McDonald, G Shroyer, ALW AF Quin, Jacquelyn A. Hattler, Brack Bishawi, Muath Baltz, Janet Gupta, Sandeep Collins, Joseph F. Grover, Frederick L. McDonald, Gerald Shroyer, A. Laurie W. TI Impact of Lipid-Lowering Medications and Low-Density Lipoprotein Levels on 1-Year Clinical Outcomes after Coronary Artery Bypass Grafting SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 98th Annual Clinical Congress of the American-College-of-Surgeons (ACS) / 67th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY SEP 30-OCT 04, 2012 CL Chicago, IL SP Amer Coll Surg ID LOW-DOSE ANTICOAGULATION; SECONDARY PREVENTION; STATIN THERAPY; CHOLESTEROL LEVELS; SURGERY; DISEASE; TRIAL; GUIDELINES; EVENTS AB BACKGROUND: Studies investigating lipid-lowering medication (LLM) use and LDL levels in coronary artery bypass grafting patients are limited. STUDY DESIGN: The Veterans Affairs Randomized On/Off Bypass Trial's patient records were analyzed for LLM use and 1-year LDL levels. Mortality, acute MI (AMI), and repeat revascularization rates were compared at 1 year between patients with and without LLM at discharge. In addition, AMI, repeat revascularization, and graft patency were compared between patients that did and did not achieve a 1-year LDL target level of <100 mg/dL. RESULTS: The LLM data were available for 86.4% (1,904 of 2,203) of patients. Rates of LLM use were 83.4% (1,316 of 1,577) at discharge and 90.0% (1,713 of 1,904) at 1 year. Patients discharged after coronary artery bypass grafting on LLMs had a significantly lower 1-year mortality rate (1.9% vs 5.4%; p < 0.01) than those not discharged on LLM, and 1-year AMI and repeat revascularization rates were not significantly different. Of the patients with 1-year LDL measurements, 69.4% (1,200 of 1,729) achieved an LDL target level of <100 mg/dL. No differences were seen in AMI, revascularization, or graft occlusion rates between patients who achieved target LDL levels and those who did not. CONCLUSIONS: Rates of LLM use among veterans post-coronary artery bypass grafting are high. Discharge on LLM might be associated with improved intermediate-term survival. Patients who achieved an LDL target of <100 mg/dL at 1-year did not experience improved 1-year clinical outcomes or graft patency. Longer-term follow-up might reveal differences in cardiac outcomes related to achievement of target LDL levels. ((c) 2013 by the American College of Surgeons) C1 [Quin, Jacquelyn A.] VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. [Hattler, Brack; Baltz, Janet; Grover, Frederick L.; Shroyer, A. Laurie W.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA. [Hattler, Brack; Grover, Frederick L.] Univ Colorado, Sch Med, Aurora, CO USA. [Bishawi, Muath; Gupta, Sandeep; Shroyer, A. Laurie W.] Northport VA Med Ctr, Northport, NY USA. [Collins, Joseph F.] Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. RP Quin, JA (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy,Mail Code 112, West Roxbury, MA 02132 USA. EM jacquelyn.quin@va.gov RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 24 TC 0 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2013 VL 217 IS 3 BP 452 EP 460 DI 10.1016/j.jamcollsurg.2013.04.030 PG 9 WC Surgery SC Surgery GA 213GK UT WOS:000324043300009 PM 23891072 ER PT J AU Hahn, RT Abraham, T Adams, MS Bruce, CJ Glas, KE Lang, RM Reeves, ST Shanewise, JS Siu, SC Stewart, W Picard, MH AF Hahn, Rebecca T. Abraham, Theodore Adams, Mark S. Bruce, Charles J. Glas, Kathryn E. Lang, Roberto M. Reeves, Scott T. Shanewise, Jack S. Siu, Samuel C. Stewart, William Picard, Michael H. TI Guidelines for Performing a Comprehensive Transesophageal Echocardiographic Examination: Recommendations from the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Transesophageal echocardiography; Comprehensive examination ID LEFT ATRIAL APPENDAGE; CONGENITAL HEART-DISEASE; PATENT FORAMEN OVALE; AORTIC-VALVE IMPLANTATION; CARDIAC SURGICAL-PATIENTS; BENZOCAINE-INDUCED METHEMOGLOBINEMIA; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; UPPER GASTROINTESTINAL ENDOSCOPY; FUNCTIONAL MITRAL REGURGITATION; OF-CARDIOLOGY FOUNDATION C1 [Hahn, Rebecca T.; Shanewise, Jack S.] Columbia Univ, New York, NY USA. [Abraham, Theodore] Johns Hopkins Univ, Baltimore, MD USA. [Adams, Mark S.; Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bruce, Charles J.] Mayo Clin, Rochester, MN USA. [Glas, Kathryn E.] Emory Univ, Sch Med, Atlanta, GA USA. [Lang, Roberto M.] Univ Chicago, Chicago, IL 60637 USA. [Reeves, Scott T.] Med Univ S Carolina, Charleston, SC 29425 USA. [Siu, Samuel C.] Univ Western Ontario, London, ON, Canada. [Stewart, William] Cleveland Clin, Cleveland, OH 44106 USA. RP Hahn, RT (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org OI Picard, Michael/0000-0002-9264-3243 FU Philips Medical Systems (Andover, MA) FX Roberto M. Lang, MD, FASE, received research support from Philips Medical Systems (Andover, MA). Scott T. Reeves, MD, MBA, FASE, edited and receives royalties for A Practical Approach to Transesophageal Echocardiography (Lippincott Williams & Wilkins, Philadelphia, PA). NR 172 TC 129 Z9 134 U1 2 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2013 VL 26 IS 9 BP 921 EP 964 DI 10.1016/j.echo.2013.07.009 PG 44 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213BO UT WOS:000324028300001 PM 23998692 ER PT J AU Klein, AL Abbara, S Agler, DA Appleton, CP Asher, CR Hoit, B Hung, J Garcia, MJ Kronzon, I Oh, JK Rodriguez, ER Schaff, HV Schoenhagen, P Tan, CD White, RD AF Klein, Allan L. Abbara, Suhny Agler, Deborah A. Appleton, Christopher P. Asher, Craig R. Hoit, Brian Hung, Judy Garcia, Mario J. Kronzon, Itzhak Oh, Jae K. Rodriguez, E. Rene Schaff, Hartzell V. Schoenhagen, Paul Tan, Carmela D. White, Richard D. TI American Society of Echocardiography Clinical Recommendations for Multimodality Cardiovascular Imaging of Patients with Pericardial Disease Endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular Computed Tomography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Pericardial disease; Echocardiography; Cardiovascular magnetic resonance; Cardiac computed tomography ID EFFUSIVE-CONSTRICTIVE PERICARDITIS; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; VENTRICULAR DIASTOLIC COLLAPSE; MITRAL ANNULAR VELOCITY; POSITRON-EMISSION-TOMOGRAPHY; CARDIAC-TAMPONADE; RESTRICTIVE CARDIOMYOPATHY; DOPPLER-ECHOCARDIOGRAPHY; CONGENITAL ABSENCE; RESPIRATORY VARIATION C1 [Klein, Allan L.; Agler, Deborah A.; Rodriguez, E. Rene; Schoenhagen, Paul; Tan, Carmela D.] Cleveland Clin, Cleveland, OH 44106 USA. [Abbara, Suhny; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Asher, Craig R.] Cleveland Clin, Weston, FL USA. [Appleton, Christopher P.] Mayo Clin, Scottsdale, AZ USA. [Oh, Jae K.; Schaff, Hartzell V.] Mayo Clin, Rochester, MN USA. [Hoit, Brian] Univ Hosp Cleveland, Med Ctr, Cleveland, OH 44106 USA. [Garcia, Mario J.] Montefiore Einstein Ctr Heart & Vasc Care, Bronx, NY USA. [Kronzon, Itzhak] Lenox Hill Hosp, New York, NY 10021 USA. [White, Richard D.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. RP Klein, AL (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org FU Toshiba; Medtronic FX Jae K. Oh, MD, FASE, has received a research grant from Toshiba and core laboratory funding from Medtronic. NR 214 TC 74 Z9 75 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2013 VL 26 IS 9 BP 965 EP + DI 10.1016/j.echo.2013.06.023 PG 63 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213BO UT WOS:000324028300002 PM 23998693 ER PT J AU Lancellotti, P Nkomo, VT Badano, LP Bergler, J Bogaert, J Davin, L Cosyns, B Coucke, P Dulgheru, R Edvardsen, T Gaemperli, O Galderisi, M Griffin, B Heidenreich, PA Nieman, K Plana, JC Port, SC Scherrer-Crosbie, M Schwartz, RG Sebag, IA Voigt, JU Wann, S Yang, PC AF Lancellotti, Patrizio Nkomo, Vuyisile T. Badano, Luigi P. Bergler, Jutta Bogaert, Jan Davin, Laurent Cosyns, Bernard Coucke, Philippe Dulgheru, Raluca Edvardsen, Thor Gaemperli, Oliver Galderisi, Maurizio Griffin, Brian Heidenreich, Paul A. Nieman, Koen Plana, Juan C. Port, Steven C. Scherrer-Crosbie, Marielle Schwartz, Ronald G. Sebag, Igal A. Voigt, Jens-Uwe Wann, Samuel Yang, Phillip C. CA European Soc Cardiology Working European Soc Cardiology Working Amer Soc Nucl Cardiology Soc Cardiovasc Magnetic Resonance Soc Cardiovasc Computed Tomography TI Expert Consensus for Multi-Modality Imaging Evaluation of Cardiovascular Complications of Radiotherapy in Adults: A Report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Radiotherapy; Echocardiography; Cardiac magnetic resonance; Nuclear cardiology; Cardiac computed tomography; Heart disease ID CORONARY-ARTERY-DISEASE; LONG-TERM SURVIVORS; SPECKLE-TRACKING ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; VENTRICULAR DIASTOLIC FUNCTION; DIFFUSE MYOCARDIAL FIBROSIS; CONGESTIVE-HEART-FAILURE; BREAST-CANCER PATIENTS; NATIVE VALVE DISEASE; HODGKINS-DISEASE AB Cardiac toxicity is one of themost concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of themost critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHDis discussed. Recommendations for the early identification andmonitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed. C1 [Lancellotti, Patrizio] CHU Sart Tilman, Univ Liege Hosp, Heart Valve Clin, Dept Cardiol,GIGA Cardiovasc Sci, B-4000 Liege, Belgium. [Nkomo, Vuyisile T.] Mayo Clin, Div Cardiovasc Dis & Internal Med, Rochester, MN USA. [Badano, Luigi P.] Univ Padua, Dept Cardiac Vasc & Thorac Sci, Padua, Italy. [Bergler, Jutta] Med Univ Vienna, Dept Cardiol, Vienna, Austria. [Bogaert, Jan] Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Radiol, Louvain, Belgium. [Davin, Laurent] CHU Sart Tilman, Dept Cardiovasc Imaging & Invas Cardiol, Liege, Belgium. [Cosyns, Bernard] Ctr Hart Vaatziekten CHVZ, B-1090 Brussels, Belgium. [Coucke, Philippe] CHU Liege, Univ Hosp, Dept Radiotherapy, Liege, Belgium. [Dulgheru, Raluca] Univ Med & Pharm Carol Davila, Emergency Univ Hosp, Dept Cardiol, Bucharest, Romania. [Edvardsen, Thor] Natl Hosp Norway, Oslo Univ Hosp, Dept Cardiol, Oslo, Norway. [Gaemperli, Oliver] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland. [Galderisi, Maurizio] Federico II Univ Hosp, Cardioangiol CCU, Dept Clin & Expt Med, Naples, Italy. [Griffin, Brian; Plana, Juan C.] Cleveland Clin, Sect Cardiovasc Imaging, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Heidenreich, Paul A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Heidenreich, Paul A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Nieman, Koen] Erasmus Univ, Med Ctr, Dept Cardiol, Rotterdam, Netherlands. [Nieman, Koen] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Port, Steven C.] Aurora Hlth Care, Aurora Cardiovasc Serv, Milwaukee, WI USA. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Schwartz, Ronald G.] Univ Rochester, Med Ctr, Div Cardiol, Dept Med, Rochester, NY 14642 USA. [Schwartz, Ronald G.] Univ Rochester, Med Ctr, Div Nucl Med, Dept Imaging Sci, Rochester, NY 14642 USA. [Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Div Cardiol, Dept Med, Montreal, PQ H3T 1E2, Canada. [Sebag, Igal A.] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ, Canada. [Voigt, Jens-Uwe] Cathol Univ Leuven, Univ Hosp Gasthuisberg, Dept Cardiovasc Dis, Louvain, Belgium. [Wann, Samuel] Columbia St Marys Healthcare, Heart Failure Program, Milwaukee, WI USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Lancellotti, P (reprint author), CHU Sart Tilman, Univ Liege Hosp, Heart Valve Clin, Dept Cardiol,GIGA Cardiovasc Sci, B-4000 Liege, Belgium. EM plancellotti@chu.ulg.ac.be RI Edvardsen, Thor/F-4079-2012; bogaert, jan/E-6181-2012; OI Edvardsen, Thor/0000-0002-3800-765X; Heidenreich, Paul/0000-0001-7730-8490; Galderisi, Maurizio/0000-0003-0311-9069; Badano, Luigi/0000-0002-0379-3283 NR 121 TC 41 Z9 44 U1 2 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2013 VL 26 IS 9 BP 1013 EP 1032 DI 10.1016/j.echo.2013.07.005 PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 213BO UT WOS:000324028300003 PM 23998694 ER PT J AU O'Donnell, MR Tallman, MS Abboud, CN Altman, JK Appelbaum, FR Arber, DA Attar, E Borate, U Coutre, SE Damon, LE Lancet, J Maness, LJ Marcucci, G Martin, MG Millenson, MM Moore, JO Ravandi, F Shami, PJ Smith, BD Stone, RM Strickland, SA Wang, ES Gregory, KM Naganuma, M AF O'Donnell, Margaret R. Tallman, Martin S. Abboud, Camille N. Altman, Jessica K. Appelbaum, Frederick R. Arber, Daniel A. Attar, Eyal Borate, Uma Coutre, Steven E. Damon, Lloyd E. Lancet, Jeffrey Maness, Lori J. Marcucci, Guido Martin, Michael G. Millenson, Michael M. Moore, Joseph O. Ravandi, Farhad Shami, Paul J. Smith, B. Douglas Stone, Richard M. Strickland, Stephen A. Wang, Eunice S. Gregory, Kristina M. Naganuma, Maoko TI Acute Myeloid Leukemia, Version 2.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; ARSENIC TRIOXIDE; CONSOLIDATION THERAPY; CHEMOTHERAPY; INTERGROUP; SURVIVAL; ADULTS; AIDA; APL AB These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Acute Myeloid Leukemia and discuss the clinical evidence that support the recommendations. The updates described in this article focus on the acute promyelocytic leukemia (APL) section, featuring recommendations for additional induction/consolidation regimens in patients with low- or intermediate-risk APL, and providing guidance on maintenance strategies for APL. C1 [O'Donnell, Margaret R.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Abboud, Camille N.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Altman, Jessica K.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Appelbaum, Frederick R.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Arber, Daniel A.; Coutre, Steven E.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Center, Seattle, WA USA. [Attar, Eyal] Stanford Canc Inst, Stanford, CA USA. [Borate, Uma] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Damon, Lloyd E.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Lancet, Jeffrey] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Maness, Lori J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Martin, Michael G.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH USA. [Martin, Michael G.] Solove Res Inst, Columbus, OH USA. [Millenson, Michael M.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN USA. [Moore, Joseph O.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Ravandi, Farhad] Duke Canc Inst, Durham, NC USA. [Shami, Paul J.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Smith, B. Douglas] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Stone, Richard M.] Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins, MD USA. [Strickland, Stephen A.] Dana Farber Canc Inst, Boston, MA USA. [Wang, Eunice S.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Wang, Eunice S.] Roswell Pk Canc Inst, Buffalo, NY USA. RP O'Donnell, MR (reprint author), City Hope Comprehens Canc Ctr, Duarte, CA USA. OI Strickland, Stephen/0000-0002-6861-2041 FU Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; ARIAD Pharmaceuticals, Inc. FX Supported by educational grants from Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; and ARIAD Pharmaceuticals, Inc. NR 22 TC 48 Z9 51 U1 0 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2013 VL 11 IS 9 BP 1047 EP 1055 PG 9 WC Oncology SC Oncology GA 216UQ UT WOS:000324310800003 PM 24029121 ER PT J AU Tichy, JR Lim, E Anders, CK AF Tichy, Jill R. Lim, Elgene Anders, Carey K. TI Breast Cancer in Adolescents and Young Adults: A Review With a Focus on Biology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID BRCA1 MUTATION CARRIERS; QUALITY-OF-LIFE; GENE-EXPRESSION; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; MOLECULAR PORTRAITS; OVARIAN-FUNCTION; AGE; CHEMOTHERAPY; RISK AB Breast cancer is a substantial contributor to adolescent and young adult (AYA) malignancies, defined as a diagnosis of cancer between the ages of 15 and 39. In the United States, 6.6% of breast cancer cases are diagnosed among women younger than 40 years. When breast cancer occurs in AYAs, it typically has a worse prognosis and more-aggressive phenotype; higher proportions of high-grade and later-stage tumors; lower estrogen receptor positivity; and, in some studies, higher expression of HER2. Age-specific differences in the biology of AYA breast cancer have been explored in large-scale genomic studies with mixed results. Although some studies suggest that AYA breast cancer has a unique biology, others have shown that its aggressive nature is the result of higher frequencies of aggressive breast cancer subtypes among younger patients. More recently, stromal-related gene signatures have shown prognostic significance in AYA breast cancer, suggesting that differences in microenvironment may account for age-specific differences in breast cancer behavior. Although general principles for selecting cytotoxic and targeted agents are similar between AYAs and the general breast cancer population, endocrine therapy choices in the adjuvant and metastatic settings vary by pre- and postmenopausal status. The role of ovarian suppression remains controversial and is reviewed. The AYA population is a unique group of patients who need individualized care, including considerations of hereditary breast cancer predispositions, future fertility, and the effect of therapy on immediate and long-term quality of life, all of which require coordinated multidisciplinary care. This article addresses the epidemiology, genetics, and management of breast cancer in AYA women and highlights unique medical issues important to this population. C1 [Tichy, Jill R.; Anders, Carey K.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Lim, Elgene] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anders, CK (reprint author), Univ N Carolina, 170 Manning Dr,CB 7305, Chapel Hill, NC 27599 USA. EM carey_anders@med.unc.edu FU National Cancer Institute [K23CA157728]; Damon Runyon Cancer Research Foundation [CI-64-12] FX The project described was supported by Grant Number K23CA157728 (CKA) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Dr. Anders is a Damon Runyon Clinical Investigator supported (in part) by the Damon Runyon Cancer Research Foundation (CI-64-12). NR 57 TC 14 Z9 14 U1 0 U2 16 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2013 VL 11 IS 9 BP 1060 EP 1069 PG 10 WC Oncology SC Oncology GA 216UQ UT WOS:000324310800004 PM 24029122 ER PT J AU Nabors, LB Ammirati, M Bierman, PJ Brem, H Butowski, N Chamberlain, MC DeAngelis, LM Fenstermaker, RA Friedman, A Gilbert, MR Hesser, D Holdhoff, M Junck, L Lawson, R Loeffler, JS Maor, MH Moots, PL Morrison, T Mrugala, MM Newton, HB Portnow, J Raizer, JJ Recht, L Shrieve, DC Sills, AK Tran, D Tran, N Vrionis, FD Wen, PY McMillian, N Ho, M AF Nabors, Louis Burt Ammirati, Mario Bierman, Philip J. Brem, Henry Butowski, Nicholas Chamberlain, Marc C. DeAngelis, Lisa M. Fenstermaker, Robert A. Friedman, Allan Gilbert, Mark R. Hesser, Deneen Holdhoff, Matthias Junck, Larry Lawson, Ronald Loeffler, Jay S. Maor, Moshe H. Moots, Paul L. Morrison, Tara Mrugala, Maciej M. Newton, Herbert B. Portnow, Jana Raizer, Jeffrey J. Recht, Lawrence Shrieve, Dennis C. Sills, Allen K. Tran, David Tran, Nam Vrionis, Frank D. Wen, Patrick Y. McMillian, Nicole Ho, Maria TI Central Nervous System Cancers Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID LOW-GRADE GLIOMA; PHASE-II TRIAL; RECURRENT MALIGNANT GLIOMA; WHOLE-BRAIN RADIOTHERAPY; REFRACTORY ANAPLASTIC ASTROCYTOMA; AVERAGE-RISK MEDULLOBLASTOMA; TERM-FOLLOW-UP; PROSPECTIVE RANDOMIZED-TRIAL; BEVACIZUMAB PLUS IRINOTECAN; MEDICAL-RESEARCH-COUNCIL AB Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume. These guidelines provide recommendations on the diagnosis and management of this group of diseases based on clinical evidence and panel consensus. This version includes expert advice on the management of low-grade infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain metastases. The full online version, available at NCCN. org, contains recommendations on additional subtypes. C1 [Nabors, Louis Burt] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL 35294 USA. [Ammirati, Mario; Newton, Herbert B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Ammirati, Mario; Newton, Herbert B.] Solove Res Inst, Columbus, OH USA. [Bierman, Philip J.] UNMC Eppley Canc Ctr, Nebraska Med Ctr, Omaha, NE USA. [Brem, Henry] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Butowski, Nicholas] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Chamberlain, Marc C.; Mrugala, Maciej M.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Fenstermaker, Robert A.] Roswell Pk Canc Inst, Buffalo, NY USA. [Friedman, Allan] Duke Canc Inst, Durham, NC USA. [Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Hesser, Deneen] Amer Brain Tumor Assoc, Washington, DC USA. [Holdhoff, Matthias] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Junck, Larry] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Maor, Moshe H.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Moots, Paul L.; Sills, Allen K.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Morrison, Tara] Fox Chase Canc Ctr, Philadelphia, PA USA. [Portnow, Jana] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Raizer, Jeffrey J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Recht, Lawrence] Stanford Canc Inst, Stanford, CA USA. [Shrieve, Dennis C.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Tran, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Tran, David] Washington Univ, Sch Med, Washington, DC USA. [Tran, Nam; Vrionis, Frank D.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Nabors, LB (reprint author), Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL 35294 USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU NCI NIH HHS [P30 CA006973] NR 180 TC 14 Z9 16 U1 3 U2 14 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2013 VL 11 IS 9 BP 1114 EP 1151 PG 38 WC Oncology SC Oncology GA 216UQ UT WOS:000324310800008 PM 24029126 ER PT J AU Brastianos, PK Curry, WT Oh, KS AF Brastianos, Priscilla K. Curry, William T. Oh, Kevin S. TI Clinical Discussion and Review of the Management of Brain Metastases SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID CELL LUNG-CANCER; NERVOUS-SYSTEM METASTASES; THERAPY-ONCOLOGY-GROUP; PHASE-II TRIAL; POSTOPERATIVE RESECTION CAVITY; RANDOMIZED CONTROLLED-TRIAL; RADIATION-THERAPY; BREAST-CANCER; STEREOTACTIC RADIOSURGERY; CEREBRAL METASTASES AB Brain metastases are common in patients with cancer and are associated with a poor prognosis. Optimal treatment requires an integrative multidisciplinary approach, and therapeutic options may include stereotactic radiosurgery, whole-brain radiation therapy, surgical resection, chemotherapy, and targeted agents. The goals of therapy are to prolong survival, preserve neurologic function, and palliate symptoms. This article outlines the various therapeutic modalities, factors that guide treatment decisions, and medical management of frequently encountered complications of brain metastases. C1 [Brastianos, Priscilla K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Oh, Kevin S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Oh, KS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM koh2@partners.org NR 116 TC 7 Z9 7 U1 2 U2 9 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2013 VL 11 IS 9 BP 1153 EP 1164 PG 12 WC Oncology SC Oncology GA 216UQ UT WOS:000324310800009 PM 24029127 ER PT J AU Eisner, B AF Eisner, Brian TI Improvements in Minimally Invasive Stone Treatment: Experimental Studies SO JOURNAL OF UROLOGY LA English DT Editorial Material ID SHOCK-WAVE LITHOTRIPSY; MECHANICAL PERCUSSION; INVERSION THERAPY; DIURESIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. RP Eisner, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2013 VL 190 IS 3 BP 834 EP 835 DI 10.1016/j.juro.2013.06.039 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 216PK UT WOS:000324295800003 PM 23791990 ER PT J AU Sterious, S Simhan, J Uzzo, RG Gershman, B Li, TY Devarajan, K Canter, D Walton, J Fogg, R Ginzburg, S Corcoran, A Smaldone, MC Kutikov, A AF Sterious, Steve Simhan, Jay Uzzo, Robert G. Gershman, Boris Li, Tianyu Devarajan, Karthik Canter, Daniel Walton, John Fogg, Ryan Ginzburg, Serge Corcoran, Anthony Smaldone, Marc C. Kutikov, Alexander TI Familiarity and Self-Reported Compliance with American Urological Association Best Practice Recommendations for Use of Thromboembolic Prophylaxis among American Urological Association Members SO JOURNAL OF UROLOGY LA English DT Article DE prevention and control; heparin; practice guidelines as topic; societies; medical; thromboembolism ID CLINICAL-PRACTICE GUIDELINES; VENOUS THROMBOEMBOLISM; RADICAL PROSTATECTOMY; PULMONARY-EMBOLISM; BLADDER-CANCER; SURGERY; THROMBOSIS; HEPARIN; PREVENTION; CYSTECTOMY AB Purpose: Thromboprophylaxis with subcutaneous heparin or low molecular weight heparin is now an integral part of national surgical quality and safety assessment efforts, and has been incorporated into the current AUA Best Practice Statement. We evaluated familiarity and compliance with the AUA Best Practice Statement, assessed practice patterns in terms of perioperative thromboprophylaxis and specifically examined self-reported compliance in high risk patients undergoing radical cystectomy. Materials and Methods: An electronic survey was sent to AUA members with valid e-mail addresses (10,966). Associations between AUA Best Practice Statement adherence and factors such as urological specialty, graduation year and guideline familiarity were assessed using chi-square analyses and generalized estimating equations. Results: With 1,210 survey responses the largest group of respondents was urological oncologists and/or laparoscopic/robotic specialists (26.0%). This group was more likely to use thromboprophylaxis than nonurological oncologists and/or laparoscopic/robotic specialists in high risk patients (OR 1.3, CI 1.1-1.5). Respondents aware of the AUA Best Practice Statement guidelines (50.7%) were more likely to use thromboprophylaxis (OR 1.4, CI 1.2-1.6). Although 18.1% of urological oncologists and/or laparoscopic/robotic specialists and 34.2% of nonurological oncologists and/or laparoscopic/robotic specialists avoided routine thromboprophylaxis in patients undergoing radical cystectomy, the former were more likely to use thromboprophylaxis (p <0.0001) than other respondents. Urologists graduating after the year 2000 used thromboprophylaxis in high risk patients undergoing radical cystectomy more often than did earlier graduates (79.2% vs 63.4%, p <0.0001). Conclusions: Although younger age and self-reported urological oncologist and/or laparoscopic/robotic specialist status correlated strongly with thromboprophylaxis use, self-reported adherence to AUA Best Practice Statement was low, even in high risk cases with clear AUA Best Practice Statement recommendations such as radical cystectomy. These data identify opportunities for quality improvement in patients undergoing major urological surgery. C1 [Sterious, Steve; Simhan, Jay; Uzzo, Robert G.; Walton, John; Fogg, Ryan; Ginzburg, Serge; Corcoran, Anthony; Smaldone, Marc C.; Kutikov, Alexander] Temple Univ, Sch Med, Fox Chase Canc Ctr, Div Urol Oncol,Dept Surg Oncol, Philadelphia, PA 19111 USA. [Li, Tianyu; Devarajan, Karthik] Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA. [Gershman, Boris] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Canter, Daniel] Emory Sch Med, Winship Canc Inst, Dept Urol, Atlanta, GA USA. RP Kutikov, A (reprint author), Temple Univ, Sch Med, Fox Chase Canc Ctr, Dept Surg Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Alexander.Kutikov@fccc.edu RI Kutikov, Alexander/L-8707-2014 FU NCI NIH HHS [P30 CA006927] NR 28 TC 15 Z9 15 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2013 VL 190 IS 3 BP 992 EP 998 DI 10.1016/j.juro.2013.03.076 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 216PK UT WOS:000324295800072 PM 23538239 ER PT J AU Moul, JW Walsh, PC Rendell, MS Lynch, HT Leslie, SW Kosoko-Lasaki, O Fitzgibbons, WP Powell, I D'Amico, AV Catalona, WJ AF Moul, Judd W. Walsh, Patrick C. Rendell, Marc S. Lynch, Henry T. Leslie, Stephen W. Kosoko-Lasaki, Omofolasade Fitzgibbons, William P. Powell, Isaac D'Amico, Anthony V. Catalona, William J. TI Re: Early Detection of Prostate Cancer: AUA guideline SO JOURNAL OF UROLOGY LA English DT Letter C1 [Moul, Judd W.] Duke Univ, Sch Med, Duke Canc Inst, Duke Prostate Ctr, Durham, NC 27710 USA. [Moul, Judd W.] Duke Univ, Sch Med, Dept Surg, Div Urol, Durham, NC USA. [Walsh, Patrick C.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. [Rendell, Marc S.; Lynch, Henry T.] Creighton Univ, Sch Med, Dept Med, Omaha, NE USA. [Lynch, Henry T.; Kosoko-Lasaki, Omofolasade] Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. [Leslie, Stephen W.] Creighton Univ, Sch Med, Dept Surg, Div Urol, Omaha, NE 68178 USA. [Kosoko-Lasaki, Omofolasade] Creighton Univ, Sch Med, Dept Surg Ophthalmol, Omaha, NE USA. [Fitzgibbons, William P.] Creighton Univ, Sch Med, Dept Family Practice, Omaha, NE USA. [Powell, Isaac] Wayne State Univ, Karmanos Canc Inst, Dept Urol, Detroit, MI USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Catalona, William J.] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. RP Moul, JW (reprint author), Duke Univ, Sch Med, Duke Canc Inst, Duke Prostate Ctr, Durham, NC 27710 USA. NR 0 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2013 VL 190 IS 3 BP 1134 EP 1137 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 216PK UT WOS:000324295800114 PM 23871525 ER PT J AU Harvey, HB Prabhakar, AM Gowda, V Oklu, R AF Harvey, H. Benjamin Prabhakar, Anand M. Gowda, Vrush Oklu, Rahmi TI Removing the Veil: Price Transparency in Interventional Radiology SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID HEALTH-CARE; COST; SERVICES; QUALITY C1 [Harvey, H. Benjamin; Prabhakar, Anand M.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging, Boston, MA 02114 USA. [Prabhakar, Anand M.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Gowda, Vrush] Univ London London Sch Econ & Polit Sci, London WC2A 2AE, England. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging, 55 Fruit St,GRB 290A, Boston, MA 02114 USA. EM roklu@partners.org NR 30 TC 3 Z9 3 U1 4 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2013 VL 24 IS 9 BP 1343 EP 1346 DI 10.1016/j.jvir.2013.05.033 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 217MM UT WOS:000324363600014 PM 23973023 ER PT J AU Salazar, GMM Walker, TG Conway, RF Yeddula, K Wicky, S Waltman, AC Kalva, SP AF Salazar, Gloria M. M. Walker, T. Gregory Conway, Raymond F. Yeddula, Kalpana Wicky, Stephan Waltman, Arthur C. Kalva, Sanjeeva P. TI Embolization of Angiographically Visible Type I and II Utero-ovarian Anastomoses during Uterine Artery Embolization for Fibroid Tumors: Impact on Symptom Recurrence and Permanent Amenorrhea SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID OVARIAN-FUNCTION; LEIOMYOMATA; AORTOGRAPHY; OUTCOMES AB Purpose: To compare the incidences of symptom recurrence and permanent amenorrhea following uterine artery embolization (UAE) for symptomatic fibroid tumors in patients with type I and II utero-ovarian anastomoses (UOAs) with versus without ovarian artery embolization (OAE). Materials and Methods: A retrospective, institutional review board approved study of 99 women who underwent UAE for symptomatic fibroid tumors from April 2005 to October 2010 was conducted to identify patients who had type I Or II UOAs at the time of UAE. Based on the embolization technique, patients were categorized into standard (ie, UAE only), combined (ie, UAE and OAE), and control (patients without UOAs who underwent UAE) groups. Data collected included patient characteristics, procedural technique and findings, symptom recurrence, secondary interventions, and permanent amenorrhea. Statistical analysis was performed with the Fisher exact test, with significance reached at P < .05. Results: Twenty patients (20.2%; mean age, 46.9 y +/- 6.3) had type I (n = 3) or II (p = 17) UOAs. Thirteen (65%) underwent UAE only (standard group) and seven (35%) underwent UAE and OAE (combined group). There were no significant differences between groups in demographics or in the incidence of permanent amenorrhea after procedures (follow-up, 561 d +/- 490). There was a significantly higher incidence of symptom recurrence in the standard group compared with the control group (P = .01), with no differences between combined and control groups (P = 1). Conclusions: There were no statistical differences in permanent amenorrhea rates in the groups studied, with significantly higher symptom recurrence rates observed when OAE was not performed in the setting of UOA. C1 [Salazar, Gloria M. M.; Walker, T. Gregory; Conway, Raymond F.; Yeddula, Kalpana; Wicky, Stephan; Waltman, Arthur C.; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. RP Salazar, GMM (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, 55 Fruit St,Gray Bigelow 293, Boston, MA 02114 USA. EM gmsalazar@partners.org NR 20 TC 2 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2013 VL 24 IS 9 BP 1347 EP 1352 DI 10.1016/j.jvir.2013.05.043 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 217MM UT WOS:000324363600015 PM 23871695 ER PT J AU Wei, Y Dimicoli, S Bueso-Ramos, C Chen, R Yang, H Neuberg, D Pierce, S Jia, Y Zheng, H Wang, H Wang, X Nguyen, M Wang, SA Ebert, B Bejar, R Levine, R Abdel-Wahab, O Kleppe, M Ganan-Gomez, I Kantarjian, H Garcia-Manero, G AF Wei, Y. Dimicoli, S. Bueso-Ramos, C. Chen, R. Yang, H. Neuberg, D. Pierce, S. Jia, Y. Zheng, H. Wang, H. Wang, X. Nguyen, M. Wang, S. A. Ebert, B. Bejar, R. Levine, R. Abdel-Wahab, O. Kleppe, M. Ganan-Gomez, I. Kantarjian, H. Garcia-Manero, G. TI Toll-like receptor alterations in myelodysplastic syndrome SO LEUKEMIA LA English DT Article DE myelodysplastic syndromes; innate immunity; Toll-like receptor; IL-8; JMJD3 ID HEMATOPOIETIC PROGENITOR CELLS; STEM-CELLS; INFLAMMATION; INHIBITION; PHENOTYPE; INFECTION; GENE AB Recent studies have implicated the innate immunity system in the pathogenesis of myelodysplastic syndromes (MDS). Toll-like receptor (TLR) genes encode key innate immunity signal initiators. We recently identified multiple genes, known to be regulated by TLRs, to be overexpressed in MDS bone marrow (BM) CD34+ cells, and hypothesized that TLR signaling is abnormally activated in MDS. We analyzed a large cohort of MDS cases and identified TLR1, TLR2 and TLR6 to be significantly overexpressed in MDS BM CD34+ cells. Deep sequencing followed by Sanger resequencing of TLR1, TLR2, TLR4 and TLR6 genes uncovered a recurrent genetic variant, TLR2-F217S, in 11% of 149 patients. Functionally, TLR2-F217S results in enhanced activation of downstream signaling including NF-kappa B activity after TLR2 agonist treatment. In cultured primary BM CD34+ cells of normal donors, TLR2 agonists induced histone demethylase JMJD3 and interleukin-8 gene expression. Inhibition of TLR2 in BM CD34+ cells from patients with lower-risk MDS using short hairpin RNA resulted in increased erythroid colony formation. Finally, RNA expression levels of TLR2 and TLR6, as well as presence of TLR2-F217S, are associated with distinct prognosis and clinical characteristics. These findings indicate that TLR2-centered signaling is deregulated in MDS, and that its targeting may have potential therapeutic benefit in MDS. C1 [Wei, Y.; Dimicoli, S.; Yang, H.; Pierce, S.; Jia, Y.; Zheng, H.; Ganan-Gomez, I.; Kantarjian, H.; Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Bueso-Ramos, C.; Nguyen, M.; Wang, S. A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Chen, R.; Wang, H.; Wang, X.] Baylor Coll Med, Dept Human Genet, Houston, TX 77030 USA. [Neuberg, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ebert, B.; Bejar, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Levine, R.; Abdel-Wahab, O.; Kleppe, M.] Mem Sloan Kettering Canc Ctr, Dept Leukemia, New York, NY 10021 USA. [Levine, R.; Abdel-Wahab, O.; Kleppe, M.] Mem Sloan Kettering Canc Ctr, Human Pathogenesis Program, New York, NY 10021 USA. [Ganan-Gomez, I.] Univ Alcala de Henares, Dept Biochem & Mol Biol, Fac Med, Alcala De Henares, Spain. RP Garcia-Manero, G (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd,Box 428, Houston, TX 77030 USA. EM ggarciam@mdanderson.org RI Kleppe, Maria/C-6341-2014; Wang, Xia/O-4036-2014; OI Kleppe, Maria/0000-0002-4372-6704; Wang, Xia/0000-0002-7750-1167; Abdel-Wahab, Omar/0000-0002-3907-6171 FU Cancer Prevention and Research Institute of Texas (CPRIT) [RP100202]; DOD/Congressionally Directed Medical Research Programs; MD Anderson Cancer Center Leukemia SPORE grant [CA100632]; Evans Foundation; MD Anderson Cancer Center CCSG [CA016672]; Regional Ministry of Education of Castilla-la Mancha, Spain; European Social Fund (ESF) FX This work was supported by grant RP100202 from the Cancer Prevention and Research Institute of Texas (CPRIT), the DOD/Congressionally Directed Medical Research Programs, the MD Anderson Cancer Center Leukemia SPORE grant CA100632, the Evans Foundation and the MD Anderson Cancer Center CCSG CA016672. IG-G was funded by the Regional Ministry of Education of Castilla-la Mancha, Spain, supported by the European Social Fund (ESF). We are thankful to Zhihong Fang, Ying Hu, and Michael Fernandez for their technical help. NR 29 TC 29 Z9 30 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2013 VL 27 IS 9 BP 1832 EP 1840 DI 10.1038/leu.2013.180 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 214UT UT WOS:000324162700006 PM 23765228 ER PT J AU Abramson, JS Takvorian, RW Fisher, DC Feng, Y Jacobsen, ED Brown, JR Barnes, JA Neuberg, DS Hochberg, EP AF Abramson, Jeremy S. Takvorian, Ronald W. Fisher, David C. Feng, Yang Jacobsen, Eric D. Brown, Jennifer R. Barnes, Jeffrey A. Neuberg, Donna S. Hochberg, Ephraim P. TI Oral clofarabine for relapsed/refractory non-Hodgkin lymphomas: results of a phase 1 study SO LEUKEMIA & LYMPHOMA LA English DT Article DE Nucleoside analog; non-Hodgkin lymphoma; follicular lymphoma; mantle cell lymphoma; marginal zone lymphoma ID MANTLE CELL LYMPHOMA; LOW-GRADE LYMPHOMA; RIBONUCLEOTIDE REDUCTASE; FLUDARABINE PHOSPHATE; RESPONSE CRITERIA; CLADRIBINE; DNA; 2-CHLORO-9-(2-DEOXY-2-FLUORO-BETA-D-ARABINOFURANOSYL)ADENINE; CHEMOTHERAPY; INHIBITION AB We conducted a phase 1 trial evaluating the oral nucleoside analog clofarabine in patients with relapsed/refractory non-Hodgkin lymphoma. Patients were treated once daily on days 1 through 21 of a 28-day cycle for a maximum of six cycles. The study was conducted with a 3 + 3 design with 10 additional patients treated at the recommended phase 2 dose. Thirty patients were enrolled including indolent B-cell lymphomas (n = 21), mantle cell lymphoma (n = 6) and diffuse large B-cell lymphoma (n = 3). The primary toxicities were hematologic including grade 3-4 neutropenia (53%) and thrombocytopenia (27%). Three milligrams was determined to be the recommended phase 2 dose. Tumor volume was reduced in 70% of patients, and the overall response rate was 47% including 27% complete remissions. Responses were seen in indolent B-cell lymphomas and mantle cell lymphoma. At a median follow-up of 17 months, 68% of responding patients remain in ongoing remission. Oral clofarabine was well tolerated with encouraging efficacy in indolent B-cell lymphomas and mantle cell lymphomas, warranting further investigation. C1 [Abramson, Jeremy S.; Takvorian, Ronald W.; Barnes, Jeffrey A.; Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. [Abramson, Jeremy S.; Takvorian, Ronald W.; Fisher, David C.; Jacobsen, Eric D.; Brown, Jennifer R.; Barnes, Jeffrey A.; Hochberg, Ephraim P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Fisher, David C.; Jacobsen, Eric D.; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Feng, Yang; Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. EM jabramson@partners.org OI Abramson, Jeremy/0000-0001-8467-9257 FU NCI NIH HHS [P30 CA006516] NR 24 TC 5 Z9 5 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2013 VL 54 IS 9 BP 1915 EP 1920 DI 10.3109/10428194.2013.763397 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 206BY UT WOS:000323492400012 PM 23289359 ER PT J AU Sadrzadeh, H Huck, AE Chen, YB Hasserjian, RP Fathi, AT AF Sadrzadeh, Hossein Huck, Amelia E. Chen, Yi-Bin Hasserjian, Robert P. Fathi, Amir T. TI Philadelphia chromosome positive B-cell lymphoblastic lymphoma isolated to bone SO LEUKEMIA & LYMPHOMA LA English DT Letter ID CHILDRENS CANCER GROUP; INTENSIVE CHEMOTHERAPY; LEUKEMIA; INVOLVEMENT C1 [Sadrzadeh, Hossein; Chen, Yi-Bin; Fathi, Amir T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Huck, Amelia E.; Hasserjian, Robert P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Fathi, AT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, 0 Emerson Pl, Boston, MA 02114 USA. EM afathi@partners.org NR 15 TC 1 Z9 1 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2013 VL 54 IS 9 BP 2052 EP 2054 DI 10.3109/10428194.2012.760735 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 206BY UT WOS:000323492400033 PM 23256565 ER PT J AU Sherman, AE Motyckova, G Fega, KR DeAngelo, DJ Abel, GA Steensma, D Wadleigh, M Stone, RM Driver, JA AF Sherman, Alexander E. Motyckova, Gabriela Fega, K. Rebecca DeAngelo, Daniel J. Abel, Gregory A. Steensma, David Wadleigh, Martha Stone, Richard M. Driver, Jane A. TI Geriatric assessment in older patients with acute myeloid leukemia: A retrospective study of associated treatment and outcomes SO LEUKEMIA RESEARCH LA English DT Article DE Geriatric assessment; Leukemia; Acute; Myeloid; Prognosis; Performance status; Comorbidity ID TRANSPLANTATION COMORBIDITY INDEX; RECEIVING INDUCTION CHEMOTHERAPY; EARLY DEATH; COMPLETE REMISSION; ELDERLY-PATIENTS; INTENSIVE CHEMOTHERAPY; MYELODYSPLASTIC SYNDROME; SURVIVAL; AGE; ADULTS AB We explored whether geriatric assessment variables predicted mortality in addition to known prognostic factors in 101 patients aged >= 65 with newly diagnosed AML. Baseline comorbidity score (HR = 1.92; 95%CI 1.18-3.11), difficulty with strenuous activity (HR = 2.18; 95%CI 1.19-4.00), and pain (HR = 2.17; 95%CI 1.19-3.97) were independent prognostic factors for greater risk of death in a multivariable model that included cytogenetic risk group. They remained independent predictors in the subset of patients with baseline ECOG PS 0-1. Our results support the use of geriatric assessment to better predict prognosis in older patients with AML, even among those with excellent functional status. Published by Elsevier Ltd. C1 [Sherman, Alexander E.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Motyckova, Gabriela; DeAngelo, Daniel J.; Abel, Gregory A.; Steensma, David; Wadleigh, Martha; Stone, Richard M.; Driver, Jane A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fega, K. Rebecca] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA. [Driver, Jane A.] Boston VA Med Ctr, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. [Driver, Jane A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Boston, MA USA. RP Driver, JA (reprint author), Boston VA Med Ctr, Geriatr Res Educ & Clin Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM jdriver@partners.org OI Steensma, David/0000-0001-5130-9284 FU Veterans' Administration Career Development award; American Federation for Aging Research Grant [1T35AG038027-02] FX Dr. Driver is funded by a Veterans' Administration Career Development award. Alexander Sherman is funded by an American Federation for Aging Research Grant #1T35AG038027-02. NR 33 TC 17 Z9 18 U1 4 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2013 VL 37 IS 9 BP 998 EP 1003 DI 10.1016/j.leukres.2013.05.013 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 213YW UT WOS:000324097600003 PM 23747082 ER PT J AU Attar, EC Amrein, PC Fraser, JW Fathi, AT McAfee, S Wadleigh, M DeAngelo, DJ Steensma, DP Stone, RM Foster, J Neuberg, D Ballen, KK AF Attar, Eyal C. Amrein, Philip C. Fraser, James W. Fathi, Amir T. McAfee, Steven Wadleigh, Martha DeAngelo, Daniel J. Steensma, David P. Stone, Richard M. Foster, Julia Neuberg, Donna Ballen, Karen K. TI Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) SO LEUKEMIA RESEARCH LA English DT Article DE Bortezomib and lenalidomide in MDS and AML ID ACUTE MYELOGENOUS LEUKEMIA; INTERNATIONAL WORKING GROUP; RESPONSE CRITERIA; STEM-CELLS; KAPPA-B; THERAPY; RISK; CYTARABINE; INDUCTION; DELETION AB We conducted a phase I dose escalation study to determine the maximal tolerated dose of bortezomib that could be combined with standard dose lenalidomide in patients with MDS or AML. Treatment consisted of bortezomib (IV) on Days 1, 4, 8, and 11 and lenalidomide 10 mg daily (PO) days 1-21 in 28 day cycles for up to 9 cycles. 23 patients (14 MDS/CMML, 9 AML) were enrolled. The maximally tested dose of bortezomib, 1.3 mg/m(2), was tolerable in this regimen. Responses were seen in patients with MDS and AML. Further testing of this regimen is planned. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Attar, Eyal C.; Amrein, Philip C.; Fraser, James W.; Fathi, Amir T.; McAfee, Steven; Foster, Julia; Ballen, Karen K.] Massachusetts Gen Hosp, Ctr Canc, Ctr Leukaemia, Boston, MA USA. [Wadleigh, Martha; DeAngelo, Daniel J.; Steensma, David P.; Stone, Richard M.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM eattar@partners.org OI Steensma, David/0000-0001-5130-9284 FU Leukemia Discovery and Treatment Fund at Massachusetts General Hospital; [CA118419-01A2] FX This study was supported in part by CA118419-01A2 (E.A) and the Leukemia Discovery and Treatment Fund at Massachusetts General Hospital. NR 19 TC 13 Z9 13 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2013 VL 37 IS 9 BP 1016 EP 1020 DI 10.1016/j.leukres.2013.05.011 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 213YW UT WOS:000324097600006 PM 23773898 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Vincent du Vigneaud - Nobel Prize in Chemistry SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN USA. OI Steensma, David/0000-0001-5130-9284 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD SEP PY 2013 VL 88 IS 9 BP E99 EP E99 DI 10.1016/j.mayocp.2012.01.032 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 217CM UT WOS:000324334200025 PM 24001505 ER PT J AU Paruthi, J Gill, N Mantzaros, CS AF Paruthi, Jason Gill, Natasha Mantzaros, Christos S. TI Adipokines in the HIV/HAART-associated lipodystrophy syndrome SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Review DE Leptin; Adiponectin; HIV; Lipodystrophy; HALS ID ACTIVE ANTIRETROVIRAL THERAPY; VIRUS-INFECTED PATIENTS; HIV-ASSOCIATED LIPODYSTROPHY; LEPTIN-REPLACEMENT THERAPY; PLACEBO-CONTROLLED TRIAL; HUMAN GROWTH-HORMONE; REVERSES INSULIN-RESISTANCE; RANDOMIZED CONTROLLED-TRIAL; INDUCED METABOLIC SYNDROME; ABNORMAL LIPID KINETICS AB The use of highly active antiretroviral therapy (HAART) in the treatment of human immunodeficiency virus has dramatically altered both the landscape of this disease and the prognosis for those affected. With more patients now receiving HAART, adverse effects such as lipodystrophy and metabolic syndrome have emerged. In HIV/HAART-associated lipodystrophy syndrome (HALS), patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Recent studies have contributed to the elucidation of the pathophysiological abnormalities seen in this syndrome and have provided guidance for the study and use of potential treatments for these patients, but widely accepted guidelines have not yet been established. Two adipokines, leptin and adiponectin, are decreased in patients with HALS and lipoatrophy or lipodystrophy. Further, recent proof-of-concept clinical trials have proven the efficacy of leptin replacement and medications that increase circulating adiponectin levels in improving the metabolic profile of HALS patients. This review article highlights recent evidence on leptin replacement and compares leptin's efficacy to that of other treatments, including metformin and thiazolidinediones, on metabolic abnormalities such as impaired insulin-glucose homeostasis associated with lipodystrophy in patients receiving HAART. It is hoped that forthcoming large phase III clinical trials will allow the addition of leptin to our therapeutic armamentarium for use in patients suffering from this disease state. (C) 2013 Elsevier Inc. All rights reserved. C1 [Paruthi, Jason; Gill, Natasha; Mantzaros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Internal Med,Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Paruthi, Jason] Harvard Univ, Sch Med, Dept Med, Mt Auburn Hosp, Boston, MA USA. [Mantzaros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Internal Med,Sect Endocrinol, Boston, MA USA. RP Mantzaros, CS (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM cmantzor@bidmc.harvard.edu NR 95 TC 12 Z9 12 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2013 VL 62 IS 9 BP 1199 EP 1205 DI 10.1016/j.metabol.2013.04.014 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214QY UT WOS:000324151800001 PM 23706880 ER PT J AU Aronis, KN Chamberland, JP Mantzoros, CS AF Aronis, Konstantinos N. Chamberland, John P. Mantzoros, Christos S. TI GLP-1 promotes angiogenesis in human endothelial cells in a dose-dependent manner, through the Akt, Src and PKC pathways SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE GLP-1; Angiogenesis; src; PKC; Akt ID GLUCAGON-LIKE PEPTIDE-1; NITRIC-OXIDE SYNTHASE; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; GROWTH-FACTOR; MYOCARDIAL-INFARCTION; VASCULAR-PERMEABILITY; LIRAGLUTIDE PROTECTS; DIABETIC-PATIENTS; WEIGHT-LOSS; IN-VITRO AB Introduction. Novel anti-diabetic medications that mimic or augment the physiological actions of GLP-1 improve cardiovascular risk factors in diabetics and GLP-1 has been proposed to have a beneficial role in the cardiovascular system. GLP-1 may have a direct cardioprotective role by decreasing infarct size and protecting from ischemia reperfusion injury while prolonging survival in rodent models. The mechanisms underlying these observations remain largely unknown. In vitro studies suggest that GLP-1 may promote endothelial cell proliferation, but no study to date has evaluated a potential direct effect of GLP-1 on angiogenesis. Specific Aim. To evaluate whether GLP-1 affects angiogenesis in humans and to elucidate underlying molecular mechanisms. Material and Methods. We utilized a 3D culture system where spherules of human umbilical vein endothelial cells (HUVECs) embedded in a collagen scaffold were treated with escalating doses of human recombinant GLP-1 (50-2000 nmol/L) and the formation of new vessels was observed and quantified. Signaling inhibitors were utilized to identify molecular pathways through which GLP-1 promotes angiogenesis. Results. We demonstrate that GLP-1 promotes angiogenesis in a dose-dependent manner. The maximum effect on angiogenesis was observed at a GLP-1 dose of 500 nmol/L, while increased angiogenesis occurred in response to doses ranging from 200 nmol/L to 1000 nmol/L. Pre-treatment of the system with Akt inhibitor IV, Bisindolylmaleimide (PKC inhibitor) and src inhibitor I resulted in a significant decrease of the GLP-1 induced angiogenesis. Conclusions. This is the first study to demonstrate that GLP-1 promotes angiogenesis in a HUVEC three dimensional in vitro model. This effect requires pharmacological doses and is mediated through the Akt, PKC and src pathways. (C) 2013 Elsevier Inc. All rights reserved. C1 [Aronis, Konstantinos N.; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Aronis, Konstantinos N.; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Aronis, Konstantinos N.; Mantzoros, Christos S.] Boston Univ, Dept Med, Boston Med Ctr, Boston, MA 02215 USA. RP Aronis, KN (reprint author), VA Boston Hlth Care Syst, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM konstantinos.aronis@bmc.org RI Aronis, Konstantinos/F-3586-2012; OI Aronis, Konstantinos/0000-0001-7189-8434; Chamberland, John/0000-0002-7862-1371 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK058785, DK079929, DK081913]; National Institute on Aging [AG032030]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX Grant Support: The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants DK058785, DK079929 and DK081913), and the National Institute on Aging (grant AG032030); as well as Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 48 TC 20 Z9 21 U1 4 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2013 VL 62 IS 9 BP 1279 EP 1286 DI 10.1016/j.metabol.2013.04.010 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 214QY UT WOS:000324151800010 PM 23684008 ER PT J AU Yang, MH Laurent, G Bause, AS Spang, R German, N Haigis, MC Haigis, KM AF Yang, Moon Hee Laurent, Gaelle Bause, Alexandra S. Spang, Robert German, Natalie Haigis, Marcia C. Haigis, Kevin M. TI HDAC6 and SIRT2 Regulate the Acetylation State and Oncogenic Activity of Mutant K-RAS SO MOLECULAR CANCER RESEARCH LA English DT Article ID IN-VIVO; DEACETYLASE; CANCER; TUBULIN; TUMORIGENESIS; MICROTUBULES; MUTATIONS AB Activating point mutations in K-RAS are extremely common in cancers of the lung, colon, and pancreas and are highly predictive of poor therapeutic response. One potential strategy for overcoming the deleterious effects of mutant K-RAS is to alter its posttranslational modification. Although therapies targeting farnesylation have been explored, and have ultimately failed, the therapeutic potential of targeting other modifications remains to be seen. Recently, it was shown that acetylation of lysine 104 attenuates K-RAS transforming activity by interfering with GEF-induced nucleotide exchange. Here, the deacetylases HDAC6 and SIRT2 were shown to regulate the acetylation state of K-RAS in cancer cells. By extension, inhibition of either of these enzymes has a dramatic impact on the growth properties of cancer cells expressing activation mutants of K-RAS. These results suggest that therapeutic targeting of HDAC6 and/or SIRT2 may represent a new way to treat cancers expressing mutant forms of K-RAS. (C) 2013 AACR. C1 [Yang, Moon Hee; Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA. [Yang, Moon Hee; Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. [Laurent, Gaelle; Bause, Alexandra S.; Spang, Robert; German, Natalie; Haigis, Marcia C.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Haigis, KM (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, 149 13th St, Charlestown, MA 02129 USA. EM marcia_haigis@hms.harvard.edu; khaigis@partners.org FU American Cancer Society [MGO-114877]; National Science Foundation Graduate Research Fellowship [1000087636]; Human Frontier Science Program; Ellison Medical Foundation New Scholar Award; NIA [R01AG032375]; Glenn Foundation for Medical Research FX This work was supported by a Research Scholar Grant (to K.M. Haigis) from the American Cancer Society (MGO-114877) and by a pilot project award from the Andrew L. Warshaw, M.D., Institute for Pancreatic Cancer Research at MGH. N. German is supported by the National Science Foundation Graduate Research Fellowship under Grant No. 1000087636. G. Laurent is supported by a fellowship from Human Frontier Science Program. M.C. Haigis was supported by Ellison Medical Foundation New Scholar Award, funding from NIA (R01AG032375), and the Glenn Foundation for Medical Research. NR 23 TC 33 Z9 34 U1 2 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2013 VL 11 IS 9 BP 1072 EP 1077 DI 10.1158/1541-7786.MCR-13-0040-T PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 219RE UT WOS:000324525500011 PM 23723075 ER PT J AU Dodd, RD Mito, JK Eward, WC Chitalia, R Sachdeva, M Ma, Y Barretina, J Dodd, L Kirsch, DG AF Dodd, Rebecca D. Mito, Jeffrey K. Eward, William C. Chitalia, Rhea Sachdeva, Mohit Ma, Yan Barretina, Jordi Dodd, Leslie Kirsch, David G. TI NF1 Deletion Generates Multiple Subtypes of Soft-Tissue Sarcoma That Respond to MEK Inhibition SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NERVE SHEATH TUMORS; ENDOTHELIAL-CELL SURVIVAL; NEUROFIBROMATOSIS TYPE-1; MOUSE MODEL; IN-VIVO; EMBRYONAL RHABDOMYOSARCOMA; MYELOPROLIFERATIVE DISEASE; MAST-CELLS; ANGIOGENESIS; CANCER AB Soft-tissue sarcomas are a heterogeneous group of tumors arising from connective tissue. Recently, mutations in the neurofibromin 1 (NF1) tumor suppressor gene were identified in multiple subtypes of human soft-tissue sarcomas. To study the effect of NF1 inactivation in the initiation and progression of distinct sarcoma subtypes, we have developed a novel mouse model of temporally and spatially restricted NF1-deleted sarcoma. To generate primary sarcomas, we inject adenovirus containing Cre recombinase into NF1(flox/flox); Ink4a/Arf(flox/flox) mice at two distinct orthotopic sites: intramuscularly or in the sciatic nerve. The mice develop either high-grade myogenic sarcomas or malignant peripheral nerve sheath tumor (MPNST)-like tumors, respectively. These tumors reflect the histologic properties and spectrum of sarcomas found in patients. To explore the use of this model for preclinical studies, we conducted a study of mitogen-activated protein kinase (MAPK) pathway inhibition with the MEK inhibitor PD325901. Treatment with PD325901 delays tumor growth through decreased cyclin D1 mRNA and cell proliferation. We also examined the effects of MEK inhibition on the native tumor stroma and find that PD325901 decreases VEGF alpha expression in tumor cells with a corresponding decrease in microvessel density. Taken together, our results use a primary tumor model to show that sarcomas can be generated by loss of NF1 and Ink4a/Arf, and that these tumors are sensitive to MEK inhibition by direct effects on tumor cells and the surrounding microenvironment. These studies suggest that MEK inhibitors should be further explored as potential sarcoma therapies in patients with tumors containing NF1 deletion. (C) 2013 AACR. C1 [Dodd, Rebecca D.; Chitalia, Rhea; Sachdeva, Mohit; Ma, Yan; Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27708 USA. [Mito, Jeffrey K.; Kirsch, David G.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA. [Eward, William C.] Duke Univ, Med Ctr, Dept Orthopaed Surg, Durham, NC 27708 USA. [Dodd, Leslie] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27708 USA. [Barretina, Jordi] Broad Inst Harvard & MIT, Cambridge, England. [Barretina, Jordi] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Barretina, Jordi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. RP Kirsch, DG (reprint author), Duke Univ, Med Ctr, Box 91006, Durham, NC 27708 USA. EM david.kirsch@duke.edu FU Children's Tumor Foundation Young Investigator Award; Liddy Shriver Sarcoma Initiative Grant; [K02-AI093866] FX This work was supported by a Children's Tumor Foundation Young Investigator Award (to R.D. Dodd), a Liddy Shriver Sarcoma Initiative Grant (to D.G. Kirsch and R.D. Dodd), and K02-AI093866 (to D.G. Kirsch). NR 51 TC 15 Z9 16 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2013 VL 12 IS 9 BP 1906 EP 1917 DI 10.1158/1535-7163.MCT-13-0189 PG 12 WC Oncology SC Oncology GA 214YE UT WOS:000324174600020 PM 23858101 ER PT J AU Chitnis, T AF Chitnis, Tanuja TI Paediatric MS is the same disease as adult MS: No SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article ID ONSET MULTIPLE-SCLEROSIS; CHILDREN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Paediat Multiple Sclerosis Ctr,Dept Chil, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Paediat Multiple Sclerosis Ctr,Dept Chil, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM tchitnis@partners.org NR 11 TC 2 Z9 2 U1 1 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2013 VL 19 IS 10 BP 1255 EP 1256 DI 10.1177/1352458513488842 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 208VM UT WOS:000323709300002 PM 23996596 ER PT J AU Grandhe, S Graves, J Mowry, EM Krupp, L Chitnis, T Yeh, EA Kuntz, N Ness, J Belman, AL Milazzo, M Gorman, M Weinstock-Guttman, B Rodriguez, M Patterson, M James, JA Waubant, E AF Grandhe, Sirisha Graves, Jennifer Mowry, Ellen M. Krupp, Lauren Chitnis, Tanuja Yeh, Eluen A. Kuntz, Nancy Ness, Jayne Belman, Anita L. Milazzo, Maria Gorman, Mark Weinstock-Guttman, Bianca Rodriguez, Moses Patterson, Marc James, Judith A. Waubant, Emmanuelle TI VIRAL AND GENETIC RISK FACTORS FOR PEDIATRIC NEUROMYELITIS OPTICA SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 18th Annual Meeting of Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS) CY MAY 31-JUN 01, 2013 CL Orlando, FL SP Americas Comm Treatment & Res Multiple Sclerosis DE neuromyelitis optica; pediatric; viral; genetic; risk factors C1 [Grandhe, Sirisha] Univ Calif San Francisco, Bakersfield, CA USA. [Graves, Jennifer; Mowry, Ellen M.; Waubant, Emmanuelle] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Krupp, Lauren; Belman, Anita L.] SUNY Stony Brook, Med Ctr, East Setauket, NY USA. [Chitnis, Tanuja] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yeh, Eluen A.] Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada. [Kuntz, Nancy] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Ness, Jayne] Childrens Hosp Alabama, Birmingham, AL USA. [Milazzo, Maria] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Gorman, Mark] Boston Childrens Hosp, Boston, MA USA. [Weinstock-Guttman, Bianca] SUNY Buffalo, Buffalo, NY 14260 USA. [Rodriguez, Moses; Patterson, Marc] Mayo Clin, Rochester, MN USA. [James, Judith A.] Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2013 VL 19 IS 10 MA P7 BP 1400 EP 1401 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 208VM UT WOS:000323709300042 ER PT J AU Weinfurtner, KM Graves, J Mowry, EM Krupp, L Chitnis, T Yeh, EA Rodriguez, M Ness, J Belman, AL Patterson, M Gorman, M Weinstock-Guttman, B James, JA Waubant, E AF Weinfurtner, Kelley M. Graves, Jennifer Mowry, Ellen M. Krupp, Lauren Chitnis, Tanuja Yeh, E. Ann Rodriguez, Moses Ness, Jayne Belman, Anita L. Patterson, Marc Gorman, Mark Weinstock-Guttman, Bianca James, Judith A. Waubant, Emmanuelle TI RISK FACTORS FOR TRANSVERSE MYELITIS COMPARED WITH MULTIPLE SCLEROSIS, NEUROMYELITIS OPTICA, AND OTHER NEUROLOGIC DISORDERS IN PEDIATRIC PATIENTS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 18th Annual Meeting of Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS) CY MAY 31-JUN 01, 2013 CL Orlando, FL SP Americas Comm Treatment & Res Multiple Sclerosis DE Epidemiology of MS; Transverse myelitis C1 [Weinfurtner, Kelley M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Graves, Jennifer; Mowry, Ellen M.; Waubant, Emmanuelle] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Krupp, Lauren; Belman, Anita L.] SUNY Stony Brook, Med Ctr, East Setauket, NY USA. [Chitnis, Tanuja] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Yeh, E. Ann] Univ Toronto, Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada. [Rodriguez, Moses; Patterson, Marc] Mayo Clin, Rochester, MN USA. [Ness, Jayne] Childrens Hosp Alabama, Birmingham, AL USA. [Gorman, Mark] Boston Childrens Hosp, Boston, MA USA. [Weinstock-Guttman, Bianca] SUNY Buffalo, Dept Neurol, Buffalo, NY 14260 USA. [James, Judith A.] Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2013 VL 19 IS 10 MA P11 BP 1403 EP 1403 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 208VM UT WOS:000323709300046 ER PT J AU Fu, YF Foden, JA Khayter, C Maeder, ML Reyon, D Joung, JK Sander, JD AF Fu, Yanfang Foden, Jennifer A. Khayter, Cyd Maeder, Morgan L. Reyon, Deepak Joung, J. Keith Sander, Jeffry D. TI High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells SO NATURE BIOTECHNOLOGY LA English DT Article ID ZINC-FINGER NUCLEASES; SYSTEMS; ENDONUCLEASE; GENERATION; BACTERIA; ARCHAEA; MICE AB Clustered, regularly interspaced, short palindromic repeat (CRISPR) RNA-guided nucleases (RGNs) have rapidly emerged as a facile and efficient platform for genome editing. Here, we use a human cell-based reporter assay to characterize off-target cleavage of CRISPR-associated (Cas) 9-based RGNs. We find that single and double mismatches are tolerated to varying degrees depending on their position along the guide RNA (gRNA)-DNA interface. We also readily detected off-target alterations induced by four out of six RGNs targeted to endogenous loci in human cells by examination of partially mismatched sites. The off-target sites we identified harbored up to five mismatches and many were mutagenized with frequencies comparable to (or higher than) those observed at the intended on-target site. Our work demonstrates that RGNs can be highly active even with imperfectly matched RNA-DNA interfaces in human cells, a finding that might confound their use in research and therapeutic applications. C1 [Fu, Yanfang; Foden, Jennifer A.; Khayter, Cyd; Maeder, Morgan L.; Reyon, Deepak; Joung, J. Keith; Sander, Jeffry D.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Fu, Yanfang; Foden, Jennifer A.; Khayter, Cyd; Maeder, Morgan L.; Reyon, Deepak; Joung, J. Keith; Sander, Jeffry D.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Fu, Yanfang; Foden, Jennifer A.; Khayter, Cyd; Maeder, Morgan L.; Reyon, Deepak; Joung, J. Keith; Sander, Jeffry D.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Fu, Yanfang; Reyon, Deepak; Joung, J. Keith; Sander, Jeffry D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM jjoung@partners.org; jsander@partners.org FU US National Institutes of Health (NIH) [DP1 GM105378, NIH R01 GM088040, NIH P50 HG005550]; Defense Advanced Research Projects Agency (DARPA) [W911NF-11-2-0056]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award FX This work was supported by a US National Institutes of Health (NIH) Director's Pioneer Award DP1 GM105378, NIH R01 GM088040, NIH P50 HG005550, Defense Advanced Research Projects Agency (DARPA) W911NF-11-2-0056, and the Jim and Ann Orr Massachusetts General Hospital Research Scholar Award. We thank S.Q. Tsai for helpful discussions and encouragement. NR 20 TC 782 Z9 849 U1 75 U2 348 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2013 VL 31 IS 9 BP 822 EP + DI 10.1038/nbt.2623 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 216TC UT WOS:000324306300022 PM 23792628 ER PT J AU Dranoff, G AF Dranoff, Glenn TI Balancing tumor immunity and inflammatory pathology SO NATURE MEDICINE LA English DT Editorial Material ID CANCER-IMMUNOTHERAPY; SAFETY; ANTI-PD-1; ANTIBODY; MELANOMA C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu FU NCI NIH HHS [P50 CA100707, P01 CA078378, P01 CA155258, R01 CA143083]; NIBIB NIH HHS [R01 EB015498] NR 16 TC 14 Z9 14 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2013 VL 19 IS 9 BP 1100 EP 1101 DI 10.1038/nm.3335 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 213TP UT WOS:000324083500019 PM 24013749 ER PT J AU Robbins, CS Hilgendorf, I Weber, GF Theurl, I Iwamoto, Y Figueiredo, JL Gorbatov, R Sukhova, GK Gerhardt, LMS Smyth, D Zavitz, CCJ Shikatani, EA Parsons, M van Rooijen, N Lin, HY Husain, M Libby, P Nahrendorf, M Weissleder, R Swirski, FK AF Robbins, Clinton S. Hilgendorf, Ingo Weber, Georg F. Theurl, Igor Iwamoto, Yoshiko Figueiredo, Jose-Luiz Gorbatov, Rostic Sukhova, Galina K. Gerhardt, Louisa M. S. Smyth, David Zavitz, Caleb C. J. Shikatani, Eric A. Parsons, Michael van Rooijen, Nico Lin, Herbert Y. Husain, Mansoor Libby, Peter Nahrendorf, Matthias Weissleder, Ralph Swirski, Filip K. TI Local proliferation dominates lesional macrophage accumulation in atherosclerosis SO NATURE MEDICINE LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; ACCELERATES ATHEROSCLEROSIS; MONOCYTE ACCUMULATION; MYOCARDIAL-INFARCTION; IN-VIVO; MICE; RECRUITMENT; PLAQUES; PATTERN; ATHEROGENESIS AB During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall(1,2). The observation that circulating monocytes give rise to lesional macrophages(3-9) has reinforced the concept that monocyte infiltration dictates macrophage buildup. Recent work has indicated, however, that macrophage accumulation does not depend on monocyte recruitment in some inflammatory contexts(10). We therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis. In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation through the involvement of scavenger receptor A (SR-A). Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease. C1 [Robbins, Clinton S.; Hilgendorf, Ingo; Weber, Georg F.; Theurl, Igor; Iwamoto, Yoshiko; Figueiredo, Jose-Luiz; Gorbatov, Rostic; Gerhardt, Louisa M. S.; Lin, Herbert Y.; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Robbins, Clinton S.; Hilgendorf, Ingo; Weber, Georg F.; Theurl, Igor; Iwamoto, Yoshiko; Figueiredo, Jose-Luiz; Gorbatov, Rostic; Gerhardt, Louisa M. S.; Lin, Herbert Y.; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA USA. [Robbins, Clinton S.; Smyth, David; Zavitz, Caleb C. J.; Shikatani, Eric A.; Husain, Mansoor] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada. [Robbins, Clinton S.; Shikatani, Eric A.; Husain, Mansoor] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Robbins, Clinton S.] Univ Toronto, Dept Immunol, Toronto, ON, Canada. [Figueiredo, Jose-Luiz; Sukhova, Galina K.; Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Parsons, Michael] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [van Rooijen, Nico] Free Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, Amsterdam, Netherlands. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM clint.robbins@utoronto.ca; fswirski@mgh.harvard.edu OI Husain, Mansoor/0000-0002-3740-6739 FU US National Institutes of Health [1R01HL095612, HHSN 268201000044C, P01-A154904, U24-CA092782, P50-CA086355]; Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research; Department of Laboratory Medicine and Pathobiology, University of Toronto; Massachusetts General Hospital Executive Committee on Research (ECOR) Postdoctoral Award; German Research Foundation; Max Kade Foundation; Boehringer Ingelheim Funds FX We thank M. Greene for secretarial assistance. We thank J. Whitsett at Cincinnati Children's Hospital Medical Center for providing Csf2rb-/- mice. This work was supported in part by US National Institutes of Health grants 1R01HL095612 (to F.K.S.) and HHSN 268201000044C, P01-A154904, U24-CA092782 and P50-CA086355 (to R.W.) and start-up funding provided by the Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research and the Department of Laboratory Medicine and Pathobiology, University of Toronto (to C.S.R.). C.S.R. was supported by the Massachusetts General Hospital Executive Committee on Research (ECOR) Postdoctoral Award. G.F.W. and I.H. were supported by the German Research Foundation. I.T. was supported by the Max Kade Foundation. L.M.S.G. was supported by the Boehringer Ingelheim Funds. NR 37 TC 286 Z9 292 U1 4 U2 51 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2013 VL 19 IS 9 BP 1166 EP 1172 DI 10.1038/nm.3258 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 213TP UT WOS:000324083500033 PM 23933982 ER PT J AU Emblem, KE Mouridsen, K Bjornerud, A Farrar, CT Jennings, D Borra, RJH Wen, PY Ivy, P Batchelor, TT Rosen, BR Jain, RK Sorensen, AG AF Emblem, Kyrre E. Mouridsen, Kim Bjornerud, Atle Farrar, Christian T. Jennings, Dominique Borra, Ronald J. H. Wen, Patrick Y. Ivy, Percy Batchelor, Tracy T. Rosen, Bruce R. Jain, Rakesh K. Sorensen, A. Gregory TI Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MAGNETIC-SUSCEPTIBILITY; ANTIANGIOGENIC THERAPY; GLIOBLASTOMA PATIENTS; TUMOR ANGIOGENESIS; KINASE INHIBITOR; MR CONTRAST; VASCULATURE; MICROCIRCULATION; MECHANISMS AB Measurement of vessel caliber by magnetic resonance imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI termed vessel architectural imaging (VAI) that exploits an overlooked temporal shift in the magnetic resonance signal, forming the basis for vessel caliber estimation, and show how this phenomenon can reveal new information on vessel type and function not assessed by any other noninvasive imaging technique. We also show how this biomarker can provide new biological insights into the treatment of patients with cancer. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation and reduce vessel calibers in patients with recurrent glioblastomas and, more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies. C1 [Emblem, Kyrre E.; Mouridsen, Kim; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Rosen, Bruce R.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Emblem, Kyrre E.; Mouridsen, Kim; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Rosen, Bruce R.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Emblem, Kyrre E.; Mouridsen, Kim; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Wen, Patrick Y.; Batchelor, Tracy T.; Rosen, Bruce R.; Jain, Rakesh K.; Sorensen, A. Gregory] Harvard Univ, Sch Med, Boston, MA USA. [Emblem, Kyrre E.; Bjornerud, Atle] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway. [Mouridsen, Kim] Univ Aarhus, Ctr Funct Integrat Neurosci, Aarhus, Denmark. [Mouridsen, Kim] Univ Aarhus, MINDLab, Aarhus, Denmark. [Bjornerud, Atle] Univ Oslo, Dept Phys, Oslo, Norway. [Borra, Ronald J. H.] Turku Univ Hosp, Med Imaging Ctr Southwest Finland, FIN-20520 Turku, Finland. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Ivy, Percy] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Batchelor, Tracy T.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sorensen, A. Gregory] Siemens Healthcare Hlth Serv, Malvern, PA USA. RP Emblem, KE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM kyrre@mmr.mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012; OI Emblem, Kyrre/0000-0002-6580-9519; Borra, Ronald/0000-0001-8072-1243 FU US Public Health Service [R21CA117079, S10RR023401, S10RR019307, S10RR019254, S10RR023043, S10RR021110, R01CA137254, R01CA129371, 5R01NS060918, K24CA125440, P0ICA80124, K25AG029415]; US National Cancer Institute [NCT00035656]; SAIC-Frederick Inc. [26XS263]; Norwegian Research Council [191088/F20]; South-Eastern Norway Regional Health Authority Grant [2013069]; Danish Research Foundation (Center of Functionally Integrative Neuroscience); Ministry of Science, Innovation and Technology Denmark (Investment Capital for University Research); Sigrid Juselius Foundation; Instrumentarium Research Foundation; Academy of Finland; Paulo Foundation; Finnish Medical Foundation; Harvard Catalyst Harvard Clinical and Translational Science Center (US National Institutes of Health Award) [UL1 RR 025758, M01-RR-01066]; Harvard University FX The authors thank T. Stylianopoulos (Department of Mechanical and Manufacturing Engineering, University of Cyprus) and J.W. Baish (Department of Mechanical and Biomedical Engineering, Bucknell University) for critical reading of this manuscript. This work was funded by the US Public Health Service (grants R21CA117079, S10RR023401, S10RR019307, S10RR019254, S10RR023043, S10RR021110, R01CA137254, R01CA129371, 5R01NS060918, K24CA125440, P0ICA80124 and K25AG029415), by the US National Cancer Institute (http://www.clinicaltrials.gov/, NCT00035656); SAIC-Frederick Inc. grant 26XS263; Norwegian Research Council grant 191088/F20; South-Eastern Norway Regional Health Authority Grant 2013069; the Danish Research Foundation (Center of Functionally Integrative Neuroscience); the Ministry of Science, Innovation and Technology Denmark (Investment Capital for University Research); the Sigrid Juselius Foundation; the Instrumentarium Research Foundation; the Academy of Finland; the Paulo Foundation; and the Finnish Medical Foundation. This work was conducted with support from Harvard Catalyst Harvard Clinical and Translational Science Center (US National Institutes of Health Award nos. UL1 RR 025758 and M01-RR-01066 and financial contributions from Harvard University and its affiliated academic healthcare centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the US National Center for Research Resources or the US National Institutes of Health. NR 27 TC 58 Z9 59 U1 1 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2013 VL 19 IS 9 BP 1178 EP 1183 DI 10.1038/nm.3289 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 213TP UT WOS:000324083500035 PM 23955713 ER PT J AU Shirozu, K Tokuda, K Marutani, E Lefer, DJ Wang, R Ichinose, F AF Shirozu, Kazuhiro Tokuda, Kentaro Marutani, Eizo Lefer, David J. Wang, Rui Ichinose, Fumito TI Cystathionine gamma-lyase deficiency protects mice from galactosamine/lipopolysaccharide-induced acute liver failure SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 2nd European Conference on the Biology of Hydrogen Sulfide CY SEP 08-11, 2013 CL Exeter, ENGLAND SP Co Biologists Ltd, Soc Free Rad Biol & Med, World Precis Instruments Inc, Unisense A/S, Stratech Sci Ltd, Cayman Chem Co, Alpha Labs Ltd, British Microcirculat Soc C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 2 TC 0 Z9 0 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 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD SEP PY 2013 VL 31 SU 2 BP S21 EP S21 DI 10.1016/j.niox.2013.06.035 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 214RA UT WOS:000324152000027 ER PT J AU Sanders, DS Lattin, DJ Read-Brown, S Tu, DC Wilson, DJ Hwang, TS Morrison, JC Yackel, TR Chiang, MF AF Sanders, David S. Lattin, Daniel J. Read-Brown, Sarah Tu, Daniel C. Wilson, David J. Hwang, Thomas S. Morrison, John C. Yackel, Thomas R. Chiang, Michael F. TI Electronic Health Record Systems in Ophthalmology Impact on Clinical Documentation SO OPHTHALMOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; INFORMATION-TECHNOLOGY; VENOUS THROMBOEMBOLISM; DIABETIC-RETINOPATHY; MEDICAL INFORMATICS; TIME UTILIZATION; DATA-COLLECTION; PHYSICIANS; ERRORS; REPRESENTATION AB Objective: To evaluate quantitative and qualitative differences in documentation of the ophthalmic examination between paper and electronic health record (EHR) systems. Design: Comparative case series. Participants: One hundred fifty consecutive pairs of matched paper and EHR notes, documented by 3 attending ophthalmologist providers. Methods: An academic ophthalmology department implemented an EHR system in 2006. Database queries were performed to identify cases in which the same problems were documented by the same provider on different dates, using paper versus EHR methods. This was done for 50 consecutive pairs of examinations in 3 different diseases: age-related macular degeneration (AMD), glaucoma, and pigmented choroidal lesions (PCLs). Quantitative measures were used to compare completeness of documenting the complete ophthalmologic examination, as well as disease-specific critical findings using paper versus an EHR system. Qualitative differences in paper versus EHR documentation were illustrated by selecting representative paired examples. Main Outcome Measures: (1) Documentation score, defined as the number of examination elements recorded for the slit-lamp examination, fundus examination, and complete ophthalmologic examination and for critical clinical findings for each disease. (2) Paired comparison of qualitative differences in paper versus EHR documentation. Results: For all 3 diseases (AMD, glaucoma, PCL), the number of complete examination findings recorded was significantly lower with paper than the EHR system (P < 0.004). Among the 3 individual examination sections (general, slit lamp, fundus) for the 3 diseases, 5 of the 9 possible combinations had significantly lower mean documentation scores with paper than EHR notes. For 2 of the 3 diseases, the number of critical clinical findings recorded was significantly lower using paper versus EHR notes (P <= 0.022). All (150/150) paper notes relied on graphical representations using annotated hand-drawn sketches, whereas no (0/150) EHR notes contained drawings. Instead, the EHR systems documented clinical findings using textual descriptions and interpretations. Conclusions: There were quantitative and qualitative differences in the nature of paper versus EHR documentation of ophthalmic findings in this study. The EHR notes included more complete documentation of examination elements using structured textual descriptions and interpretations, whereas paper notes used graphical representations of findings. C1 [Sanders, David S.; Lattin, Daniel J.; Read-Brown, Sarah; Tu, Daniel C.; Wilson, David J.; Hwang, Thomas S.; Morrison, John C.; Chiang, Michael F.] Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, Portland, OR 97239 USA. [Tu, Daniel C.] Portland VA Med Ctr, Ophthalmol Operat Care Div, Portland, OR USA. [Yackel, Thomas R.; 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, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM chiangm@ohsu.edu OI Read-Brown, Sarah/0000-0002-6526-2939 FU Research to Prevent Blindness, Inc, New York, New York FX Supported by unrestricted departmental funding from Research to Prevent Blindness, Inc, New York, New York (D.S.S., S.R.B., D.C.T., D.J.W., T.S.H., J.C.M., and M.F.C.). The funding organization had no role in the design or conduct of this research. NR 39 TC 8 Z9 8 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2013 VL 120 IS 9 BP 1745 EP 1755 DI 10.1016/j.ophtha.2013.02.017 PG 11 WC Ophthalmology SC Ophthalmology GA 213HG UT WOS:000324045800025 PM 23683945 ER PT J AU Schallhorn, J Haug, SJ Yoon, MK Porco, T Seiff, SR McCulley, TJ AF Schallhorn, Julie Haug, Sara J. Yoon, Michael K. Porco, Travis Seiff, Stuart R. McCulley, Timothy J. TI A National Survey of Practice Patterns Temporal Artery Biopsy SO OPHTHALMOLOGY LA English DT Article ID GIANT-CELL ARTERITIS; FACIAL-NERVE INJURY; CORTICOSTEROID TREATMENT; THERAPY; YIELD AB Objective: To assess current clinical practice patterns for temporal artery biopsy (TAB) among clinicians in establishing the diagnosis of giant cell arteritis. Design: A survey was sent via e-mail using the Survey Monkey website (www.surveymonkey.com; accessed January 24, 2013). The survey initially was sent in July 2010 and continued through October 2010. Participants: The survey was sent via e-mail to the members and affiliates of the American Society of Ophthalmic Plastic and Reconstructive Surgery, the North American Neuro-Ophthalmology Society, and the American College of Rheumatology. Methods: Data from the survey were collected via Survey Monkey and data analysis was performed using the Fisher exact test and Wilcoxon rank-sum test. Main Outcome Measures: Response to the survey questions on primary unilateral versus bilateral biopsy, performing second-side biopsy if first side results were negative, and the duration for which biopsy findings are reliable after initiating immunosuppressive therapy. Results: The self-described primary subspecialty of the 1074 respondents was as follows: oculoplastic surgery (n = 127), neuro-ophthalmology (n = 119), rheumatology (n = 799), and other (n = 28). Overall, 66% of respondents advocated initial unilateral TAB, 18% advocated bilateral biopsy in all cases, and 16% recommended either unilateral or bilateral TAB depending on the degree of clinical suspicion. Rheumatologists were 4.5 times more likely to advocate initial bilateral biopsy than neuro-ophthalmologists or oculoplastic surgeons (P < 0.0001, Fisher exact test). Most respondents believed that biopsy results were accurate for more than 14 days. These results were not affected by stratification of years in practice by the Kruskal-Wallis rank-sum test. Conclusions: Temporal artery biopsy practices vary greatly among treating physicians. This lack of consensus underscores the need for a systematic assessment of varying practice patterns. (C) 2013 by the American Academy of Ophthalmology. C1 [Schallhorn, Julie; Haug, Sara J.; Porco, Travis; Seiff, Stuart R.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. [Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Seiff, Stuart R.] Calif Pacific Med Ctr, San Francisco, CA USA. [McCulley, Timothy J.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [McCulley, Timothy J.] King Khalid Eye Specialist Hosp, Riyadh, Saudi Arabia. RP McCulley, TJ (reprint author), Johns Hopkins Sch Med, Wilmer Eye Inst, 600 North Wolfe St,Wilmer 110, Baltimore, MD 21287 USA. EM tmccull5@jhmi.edu FU Research to Prevent Blindness, Inc, New York, New York FX Supported in part by an unrestricted grant to the Wilmer Ophthalmological Institute from Research to Prevent Blindness, Inc, New York, New York. NR 22 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2013 VL 120 IS 9 BP 1930 EP 1934 DI 10.1016/j.ophtha.2013.01.052 PG 5 WC Ophthalmology SC Ophthalmology GA 213HG UT WOS:000324045800050 PM 23622876 ER PT J AU Lerman, MA Xie, WL Treister, NS Richardson, PG Weller, EA Woo, SB AF Lerman, Mark A. Xie, Wanling Treister, Nathaniel S. Richardson, Paul G. Weller, Edie A. Woo, Sook-Bin TI Conservative management of bisphosphonate-related osteonecrosis of the jaws: Staging and treatment outcomes SO ORAL ONCOLOGY LA English DT Article DE Bisphosphonate-related osteonecrosis of the jaws ID NUMB-CHIN SYNDROME; MULTIPLE-MYELOMA; SURGICAL RESECTION; CANCER-PATIENTS; SINGLE-CENTER; EXPERIENCE; NECROSIS; BIPHOSPHONATES; THERAPY; VARIANT AB Objective: Bisphosphonate-related osteonecrosis of the jaws is a well-established disorder in which patients treated with bisphosphonates develop exposed necrotic bone in the oral cavity. The objective of this study was to report staging and treatment outcomes in a large cohort of patients with bisphosphonate-related osteonecrosis of the jaws managed primarily with non-surgical measures. Patients and methods: A retrospective medical record review was conducted from 1998 to 2010 of all patients referred for the management of bisphosphonate-related osteonecrosis of the jaws. Clinical findings and staging were assessed at initial consultation and each follow-up visit. Management was provided to minimize symptoms and/or achieve resolution of lesions. Treatment responses were defined based on symptoms and/or change in staging. Results: There were 120 records reviewed and 97 patients seen for follow-up (median 12 months); 90% were cancer patients. Bisphosphonate-related osteonecrosis of the jaws was managed with observation (16%), antibiotics (55%), non-surgical sequestrectomy +/- antibiotics (14%), or surgery +/- antibiotics (14%). There were 14 patients (12%) who presented with stage 0 disease; 41%, 43%, and 5% of patients presented at stages 1, 2, and 3, respectively. Greater than 70% of patients improved, remained asymptomatic, and/or showed complete re-epithelialization when evaluated at 0-3, 3-6, 6-9, 9-12, and/or > 12 months. Seventeen patients developed non-infectious complications of BONJ including neuropathy (N = 9), painful tongue ulcers (N = 7), or pathologic fracture (N = 1). Twelve patients with multiple myeloma underwent hematopoietic cell transplantation without infectious complications. Conclusions: A primarily non-surgical approach appears to be a successful management strategy for bisphosphonate-related osteonecrosis of the jaws. Overall, 71-80% of patients improved or remained asymptomatic with a median follow-up of 12 months. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Lerman, Mark A.; Treister, Nathaniel S.; Woo, Sook-Bin] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02120 USA. [Lerman, Mark A.; Treister, Nathaniel S.; Woo, Sook-Bin] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Xie, Wanling; Richardson, Paul G.; Weller, Edie A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Lerman, MA (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1 Brigham Circle,Suite 3-028, Boston, MA 02120 USA. EM Mark_Lerman@hsdm.harvard.edu NR 41 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD SEP PY 2013 VL 49 IS 9 BP 977 EP 983 DI 10.1016/j.oraloncology.2013.05.012 PG 7 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 213HJ UT WOS:000324046200022 PM 23830962 ER PT J AU Tucker, RP Wingate, LR O'Keefe, VM Mills, AC Rasmussen, K Davidson, CL Grant, DM AF Tucker, Raymond P. Wingate, LaRicka R. O'Keefe, Victoria M. Mills, Adam C. Rasmussen, Kathy Davidson, Collin L. Grant, DeMond M. TI Rumination and suicidal ideation: The moderating roles of hope and optimism SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Rumination; Hope; Optimism; Suicide; Suicidal ideation; Brooding; Reflection ID COLLEGE-STUDENTS; DEPRESSED MOOD; RISK; HOPELESSNESS; REFLECTION; SYMPTOMS; HISTORY; LIFE AB The current study aimed to investigate whether the correlation between rumination and suicidal ideation is moderated by the presence of hope and optimism. It was hypothesized that both hope and optimism would moderate (weaken) the relationship between rumination and suicidal ideation. Two hundred and ninety-eight participants completed self-report measures of hope, optimism, rumination (brooding and reflection), and depression. Results demonstrated that both hope and optimism weakened the relationship between rumination and suicidal ideation, as well as the relationships between both subscales of rumination and suicidal thinking. These results were found when controlling for symptoms of depression. Results suggest that a ruminative thinking style may be most harmful when an absence of hope or optimism is also present. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Tucker, Raymond P.; Wingate, LaRicka R.; O'Keefe, Victoria M.; Mills, Adam C.; Rasmussen, Kathy; Grant, DeMond M.] Oklahoma State Univ, Dept Psychol, Stillwater, OK 74078 USA. [Davidson, Collin L.] Denver VA Med Ctr, VA VISN MIRECC 19, Denver, CO USA. RP Wingate, LR (reprint author), Oklahoma State Univ, Dept Psychol, 116 North Murray Hall, Stillwater, OK 74078 USA. EM laricka.wingate@okstate.edu OI Grant, DeMond/0000-0002-5231-6563 NR 38 TC 13 Z9 15 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD SEP PY 2013 VL 55 IS 5 BP 606 EP 611 DI 10.1016/j.paid.2013.05.013 PG 6 WC Psychology, Social SC Psychology GA 191JZ UT WOS:000322410500028 ER PT J AU Breton, S Brown, D AF Breton, Sylvie Brown, Dennis TI Regulation of Luminal Acidification by the V-ATPase SO PHYSIOLOGY LA English DT Review ID VACUOLAR H+-ATPASE; RENAL TUBULAR-ACIDOSIS; MEDULLARY COLLECTING DUCT; EPIDIDYMAL CLEAR CELLS; ANGIOTENSIN-CONVERTING ENZYME; TRANSCRIPTION FACTOR FOXI1; BLOWFLY SALIVARY-GLANDS; MALE REPRODUCTIVE-TRACT; PROTEIN-KINASE-A; SECRETORY INTERCALATED CELLS AB Specialized cells in the body express high levels of V-ATPase in their plasma membrane and respond to hormonal and nonhormonal cues to regulate extracellular acidification. Mutations in or loss of some V-ATPase subunits cause several disorders, including renal distal tubular acidosis and male infertility. This review focuses on the regulation of V-ATPase-dependent luminal acidification in renal intercalated cells and epididymal clear cells, which are key players in these physiological processes. C1 [Breton, Sylvie] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. FU National Institutes of Health [HD-040793, DK-097124, DK-038452, DK-042956]; Center for the Study of Inflammatory Bowel Disease [DK43351]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Charles and Ann Sanders MGH Scholars Award FX This work was supported by National Institutes of Health grants HD-040793 and DK-097124 (to S. Breton), DK-038452 (to S. Breton and D. Brown), and DK-042956 (to D. Brown). The imaging work was performed in the Microscopy Core Facility of the Massachusetts General Hospital Program in Membrane Biology, which was partially supported by Center for the Study of Inflammatory Bowel Disease Grant DK43351 and Boston Area Diabetes and Endocrinology Research Center award DK57521. S. Breton is a recipient of the Charles and Ann Sanders MGH Scholars Award. NR 162 TC 49 Z9 50 U1 2 U2 20 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD SEP PY 2013 VL 28 IS 5 BP 318 EP 329 DI 10.1152/physiol.00007.2013 PG 12 WC Physiology SC Physiology GA 213XR UT WOS:000324094400008 PM 23997191 ER PT J AU Bauer, MR Ruef, AM Pineles, SL Japuntich, SJ Macklin, ML Lasko, NB Orr, SP AF Bauer, Margaret R. Ruef, Anna M. Pineles, Suzanne L. Japuntich, Sandra J. Macklin, Michael L. Lasko, Natasha B. Orr, Scott P. TI Psychophysiological Assessment of PTSD: A Potential Research Domain Criteria Construct SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE posttraumatic stress disorder; PTSD; psychophysiology; reliability; depression ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY DISORDERS; COMBAT VETERANS; IMAGERY; MOOD AB Most research on posttraumatic stress disorder (PTSD) relies on clinician-administered interview and self-report measures to establish the presence/absence and severity of the disorder. Accurate diagnosis of PTSD is made challenging by the presence of symptoms shared with other psychopathologies and the subjective nature of patients' descriptions of their symptoms. A physiological assessment capable of reliably "diagnosing" PTSD could provide adjunctive information that might mitigate these diagnostic limitations. In the present study, we examined the construct validity of a potential psychophysiological measure of PTSD, that is, psychophysiological reactivity to script-driven imagery (SDI-PR), as measured against the current diagnostic "gold-standard" for PTSD, the Clinician-Administered PTSD Scale (CAPS). Convergent and predictive validity and stability were examined. Thirty-six individuals completed an SDI-PR procedure, the CAPS, and self-report measures of mental and physical health at their initial visit and approximately 6 months later. SDI PR and the CAPS demonstrated excellent stability across measurement occasions. SDI PR showed moderately strong convergent validity with the CAPS. After adjusting for self-reported depression, predictive validity for the CAPS, with regard to health sequelae, was reduced, whereas it remained mostly unchanged for SDI-PR. Findings support SDI-PR as a valid and stable measure of PTSD that captures a pathophysiologic process in individuals with PTSD. Results are discussed with regard to the research domain criteria framework. C1 [Bauer, Margaret R.; Pineles, Suzanne L.; Japuntich, Sandra J.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Ruef, Anna M.; Macklin, Michael L.; Lasko, Natasha B.; Orr, Scott P.] Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. [Pineles, Suzanne L.; Japuntich, Sandra J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Lasko, Natasha B.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lasko, Natasha B.; Orr, Scott P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Orr, SP (reprint author), Massachusetts Gen Hosp E, Bldg 120,2nd Ave, Charlestown, MA 02129 USA. EM Scott_Orr@hms.harvard.edu NR 30 TC 7 Z9 7 U1 18 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 2013 VL 25 IS 3 BP 1037 EP 1043 DI 10.1037/a0033432 PG 7 WC Psychology, Clinical SC Psychology GA 212PH UT WOS:000323994800035 PM 23815110 ER PT J AU Kells, M Rogers, J Oppenheimer, SC Blaine, K McCabe, M McGrath, E Woodring, B Geller, AC AF Kells, Meredith Rogers, Jayne Oppenheimer, Sarah C. Blaine, Kevin McCabe, Margaret McGrath, Ellen Woodring, Barbara Geller, Alan C. TI The Teachable Moment Captured: A Framework for Nurse-led Smoking Cessation Interventions for Parents of Hospitalized Children SO PUBLIC HEALTH NURSING LA English DT Article DE motivational interviewing; nurses; secondhand smoke; smoking cessation counseling; teachable moment ID ENVIRONMENTAL TOBACCO-SMOKE; RESPIRATORY ILLNESS; CONTROLLED-TRIAL; EXPOSURE; MOTHERS AB This article explores the topic of smoking cessation counseling for parents in the context of pediatric hospitalization. Teachable moments, a widely used concept in the literature, uses three key concepts including perception of risk, emotional response, and self-concept to precipitate change (McBride, Health Education Research, 18 [McBride, 2003], 156-170). The interweaving of these concepts with institutional systems; clinically trained personnel; parental smoking considerations; parent presence; and external supports, or collectively the novel idea of the capturable moment, may allow for an increased rate of parental smoking cessation. Using these concepts, the authors constructed a hospital model for pediatric nursing efforts in parental smoking cessation. The pilot study built on this framework in February 2010 began enrolling parents of hospitalized pediatric patients into two intervention groups to motivate smoking cessation. Starting in September 2010, new electronic medical record-based systems of identifying parents who smoke were implemented in the hopes of enhancing enrollment numbers and streamlining recruitment. It is hoped that by introducing this process and framework, there will be increased national dialogue related to secondhand smoke (SHS) exposure, routine screening for SHS exposure, and nursing recognition of teachable moments. C1 [Kells, Meredith; Rogers, Jayne; McCabe, Margaret; McGrath, Ellen] Childrens Hosp Boston, Boston, MA 02115 USA. [Blaine, Kevin; Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Woodring, Barbara] Georgia State Univ, Atlanta, GA 30303 USA. [Oppenheimer, Sarah C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kells, M (reprint author), Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. EM Meredith.kells@childrens.harvard.edu FU Flight Attendant Medical Research Institute FX Extramural funding: Flight Attendant Medical Research Institute. NR 21 TC 4 Z9 4 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0737-1209 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD SEP PY 2013 VL 30 IS 5 BP 468 EP 473 DI 10.1111/phn.12046 PG 6 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA 210MQ UT WOS:000323838200013 PM 24000921 ER PT J AU Bentley, JP Brown, CJ McGwin, G Sawyer, P Allman, RM Roth, DL AF Bentley, John P. Brown, Cynthia J. McGwin, Gerald, Jr. Sawyer, Patricia Allman, Richard M. Roth, David L. TI Functional status, life-space mobility, and quality of life: a longitudinal mediation analysis SO QUALITY OF LIFE RESEARCH LA English DT Article DE Wilson-Cleary model; Activities of daily living; Mobility; SF-12; Longitudinal mediation; Autoregressive mediation modeling ID STRUCTURAL EQUATION MODEL; DWELLING OLDER-ADULTS; CONCEPTUAL-MODEL; PREDICTORS; DEPRESSION; VARIABLES; SURVIVORS; DECLINES; SURGERY; PANEL AB Using the Wilson-Cleary model of patient outcomes as a conceptual framework, the impact of functional status on health-related quality of life (HRQoL) among older adults was examined, including tests of the mediation provided by life-space mobility. Participants were enrollees in a population-based, longitudinal study of mobility among community-dwelling older adults. Data from four waves of the study equally spaced approximately 18 months apart (baseline, 18, 36, and 54 months) were used for participants who survived at least 1 year beyond the 54-month assessment (n = 677). Autoregressive mediation models using longitudinal data and cross-sectional mediation models using baseline data were evaluated and compared using structural equation modeling. The longitudinal autoregressive models supported the mediating role of life-space mobility and suggested that this effect is larger for the mental component summary score than the physical component summary score of the SF-12. Evidence for a reciprocal relationship over time between functional status, measured by ADL difficulty, and life-space mobility was suggested by modification indices; these model elaborations did not alter the substantive meaning of the mediation effects. Mediated effect estimates from longitudinal autoregressive models were generally larger than those from cross-sectional models, suggesting that mediating relationships would have been missed or were potentially underestimated in cross-sectional models. These results support a mediating role for life-space mobility in the relationship between functional status and HRQoL. Functional status limitations might cause diminished HRQoL in part by limiting mobility. Mobility limitations may precede functional status limitations in addition to being a consequence thereof. C1 [Bentley, John P.] Univ Mississippi, Sch Pharm, University, MS 38677 USA. [Brown, Cynthia J.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Brown, Cynthia J.; Sawyer, Patricia] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [McGwin, Gerald, Jr.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA. [Allman, Richard M.] Univ Alabama Birmingham, Atlanta VA Geriatr Res Educ & Clin Ctr, Ctr Aging, Birmingham, AL 35294 USA. [Allman, Richard M.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Roth, David L.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD 21205 USA. RP Bentley, JP (reprint author), Univ Mississippi, Sch Pharm, Faser Hall 235, University, MS 38677 USA. EM phjpb@olemiss.edu FU National Institute on Aging [R01 AG015062] FX The UAB Study of Aging is funded through a grant from the National Institute on Aging (R01 AG015062). NR 59 TC 14 Z9 15 U1 7 U2 35 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD SEP PY 2013 VL 22 IS 7 BP 1621 EP 1632 DI 10.1007/s11136-012-0315-3 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 214BL UT WOS:000324105100011 PM 23161329 ER PT J AU Stalcup, ST Tuan, AS Hesselink, JR AF Stalcup, Seth T. Tuan, August S. Hesselink, John R. TI Intracranial Causes of Ophthalmoplegia: The Visual Reflex Pathways SO RADIOGRAPHICS LA English DT Article ID OCULAR MOTOR MONONEUROPATHIES; ARGYLL ROBERTSON PUPIL; INTERNUCLEAR OPHTHALMOPLEGIA; SUPERFICIAL SIDEROSIS; HORNERS-SYNDROME; BRAIN-STEM; MRI; MOVEMENTS; LESIONS; PALSY AB The gathering of visual information is a complex process that relies on concerted movements of the eyes, and cranial nerves II-VIII are at least partially involved in the visual system. The cranial nerves do not function in isolation, however, and there are multiple higher-order cortical centers that have input into the cranial nerves to coordinate eye movement. Among the functions of the cortical reflex pathways are (a) controlling vertical and horizontal gaze in response to vestibular input to keep the eyes focused on an object as the head moves through space, and (b) controlling rapid, coordinated eye movement to a new visual target (saccades). There are also reflex pathways connecting the cranial nerves involved in vision that produce consensual blinking of the eyes in response to corneal stimulation of one eye and consensual pupillary constriction in response to light input on one pupil. A variety of intracranial pathologic conditions, including benign and malignant neoplasms, infection, trauma, autoimmune diseases, vascular anomalies, degenerative diseases, and inherited-congenital disorders, can disrupt the cranial nerves and visual reflex pathways. This disruption can manifest in myriad ways. for example, as extraocular muscle paresis, afferent pupillary defect, oculosympathetic paresis (Horner syndrome), internuclear ophthalmoplegia, dorsal midbrain (Parinaud) syndrome, or loss of the corneal reflex. Knowledge of the function and anatomy of the cranial nerves and visual reflex pathways, coupled with selection of the proper magnetic resonance pulse sequence, will allow the radiologist to order appropriate imaging of the involved cranial nerve or visual reflex pathway based on the patient's symptoms and thereby play an essential role in establishing the diagnosis and planning appropriate therapy. ((C))RSNA, 2013 . radiographics.rsna.org C1 [Stalcup, Seth T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Tuan, August S.; Hesselink, John R.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. RP Stalcup, ST (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM sstalcup@partners.org NR 40 TC 3 Z9 3 U1 4 U2 10 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2013 VL 33 IS 5 BP E153 EP E169 DI 10.1148/rg.335125142 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216UZ UT WOS:000324311900003 PM 24025940 ER PT J AU Moyer, CE Delevich, KM Fish, KN Asafu-Adjei, JK Sampson, AR Dorph-Petersen, KA Lewis, DA Sweet, RA AF Moyer, Caitlin E. Delevich, Kristen M. Fish, Kenneth N. Asafu-Adjei, Josephine K. Sampson, Allan R. Dorph-Petersen, Karl-Anton Lewis, David A. Sweet, Robert A. TI Intracortical excitatory and thalamocortical boutons are intact in primary auditory cortex in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE VGluT1; VGluT2; Primary auditory cortex; Quantitative microscopy; Stereology; Postmortem human tissue ID VESICULAR GLUTAMATE TRANSPORTERS; MISMATCH NEGATIVITY GENERATION; MESSENGER-RNA EXPRESSION; DENDRITIC SPINE DENSITY; SUPERIOR TEMPORAL GYRUS; RAT HIPPOCAMPAL SLICES; PREFRONTAL CORTEX; PLANUM TEMPORALE; HESCHL GYRUS; IN-VIVO AB Schizophrenia is associated with auditory processing impairments that could arise as a result of primary auditory cortex excitatory circuit pathology. We have previously reported a deficit in dendritic spine density in deep layer 3 of primary auditory cortex in subjects with schizophrenia. As boutons and spines can be structurally and functionally co-regulated, we asked whether the densities of intracortical excitatory or thalamocortical presynaptic boutons are also reduced. We studied 2 cohorts of subjects with schizophrenia and matched controls, comprising 27 subject pairs, and assessed the density, number, and within-bouton vesicular glutamate transporter (VGluT) protein level of intracortical excitatory (VGluT1-immunoreactive) and thalamocortical (VGluT2-immunoreactive) boutons in deep layer 3 of primary auditory cortex using quantitative confocal microscopy and stereologic sampling methods. We found that VGluT1- and VGluT2-immunoreactive puncta densities and numbers were not altered in deep layer 3 of primary auditory cortex of subjects with schizophrenia. Our results indicate that reduced dendritic spine density in primary auditory cortex of subjects with schizophrenia is not matched by a corresponding reduction in excitatory bouton density. This suggests excitatory boutons in primary auditory cortex in schizophrenia may synapse with structures other than spines, such as dendritic shafts, with greater frequency. The discrepancy between dendritic spine reduction and excitatory bouton preservation may contribute to functional impairments of the primary auditory cortex in subjects with schizophrenia. (C) 2013 Elsevier B.V. All rights reserved. C1 [Moyer, Caitlin E.; Fish, Kenneth N.; Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15213 USA. [Moyer, Caitlin E.; Delevich, Kristen M.; Fish, Kenneth N.; Dorph-Petersen, Karl-Anton; Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Asafu-Adjei, Josephine K.; Sampson, Allan R.] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15213 USA. [Dorph-Petersen, Karl-Anton] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark. [Dorph-Petersen, Karl-Anton] Aarhus Univ, Ctr Stochast Geometry & Adv Bioimaging, Aarhus, Denmark. [Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15213 USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Rm W1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM SweetRA@upmc.edu RI Lewis, David/G-4053-2014; Dorph-Petersen, Karl-Anton/A-9039-2015; OI Lewis, David/0000-0002-3225-6778; Dorph-Petersen, Karl-Anton/0000-0002-6676-034X; Moyer, Caitlin/0000-0002-2571-2595; Delevich, Kristen/0000-0001-5698-0093 FU [MH071533]; [MH084053]; [MH085108] FX This work was supported by Grants MH071533 (RAS), MH084053 (DAL), and MH085108 (KNF). NR 57 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2013 VL 149 IS 1-3 BP 127 EP 134 DI 10.1016/j.schres.2013.06.024 PG 8 WC Psychiatry SC Psychiatry GA 211UQ UT WOS:000323937200020 PM 23830684 ER PT J AU Hiremath, SV Ding, D Farringdon, J Vyas, N Cooper, RA AF Hiremath, S. V. Ding, D. Farringdon, J. Vyas, N. Cooper, R. A. TI Physical activity classification utilizing SenseWear activity monitor in manual wheelchair users with spinal cord injury SO SPINAL CORD LA English DT Article DE spinal cord injury; physical activity; manual wheelchair users; machine learning; energy expenditure; multisensor activity monitor ID ENERGY-EXPENDITURE AB Study design: Validation. Objectives: The primary aim of this study was to develop and evaluate activity classification algorithms for a multisensor-based SenseWear (SW) activity monitor that can recognize wheelchair-related activities performed by manual wheelchair users (MWUs) with spinal cord injury (SCI). The secondary aim was to evaluate how the accuracy in activity classification affects the estimation of energy expenditure (EE) in MWUs with SCI. Setting: University-based laboratory. Methods: Forty-five MWUs with SCI wore a SW on their upper arm and participated in resting, wheelchair propulsion, arm-ergometery and deskwork activities. The investigators annotated the start and end of each activity trial while the SW collected multisensor data and a portable metabolic cart collected criterion EE. Three methods including linear discriminant analysis, quadratic discriminant analysis (QDA), and Naive Bayes (NB) were used to develop classification algorithms for four activities based on the training data set from 36 subjects. Results: The classification accuracy was 96.3% for QDA and 94.8% for NB when the classification algorithms were tested on the validation data set from nine subjects. The average EE estimation errors using the activity-specific EE prediction model were 5.3 +/- 21.5% and 4.6 +/- 22.8% when the QDA and NB classification algorithms were applied, respectively, as opposed to 4.9 +/- 20.7% when 100% classification accuracy was assumed. Conclusion: The high classification accuracy and low EE estimation errors suggest that the SW can be used by researchers and clinicians to classify and estimate the EE for the four activities tested in this study among MWUs with SCI. C1 [Hiremath, S. V.; Ding, D.; Cooper, R. A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA 15206 USA. [Hiremath, S. V.; Ding, D.; Cooper, R. A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Ding, D.; Cooper, R. A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Farringdon, J.; Vyas, N.] BodyMedia Inc, Pittsburgh, PA USA. RP Ding, D (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM dad5@pitt.edu OI Farringdon, Jonathan/0000-0001-5977-3700 FU Rehabilitation Engineering Research Center on Interactive Exercise & Recreation Technologies & Exercise Physiology benefitting Persons with Disabilities [H133E120005]; National Institute on Disability and Rehabilitation Research (NIDRR); Switzer Research Fellowship [H133Fl10032]; NIDRR; VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering [B3142C] FX The work is supported by the Rehabilitation Engineering Research Center on Interactive Exercise & Recreation Technologies & Exercise Physiology benefitting Persons with Disabilities (H133E120005) funded by the National Institute on Disability and Rehabilitation Research (NIDRR). Mr. Hiremath's work on this article was also funded through the Switzer Research Fellowship (H133Fl10032) awarded by the NIDRR. The work is also supported by the VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering (B3142C). The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 18 TC 7 Z9 7 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD SEP PY 2013 VL 51 IS 9 BP 705 EP 709 DI 10.1038/sc.2013.39 PG 5 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 216UB UT WOS:000324309000011 PM 23689386 ER PT J AU Singh, K Nandyala, SV Marquez-Lara, A Cha, TD Khan, SN Fineberg, SJ Pelton, MA AF Singh, Kern Nandyala, Sreeharsha V. Marquez-Lara, Alejandro Cha, Thomas D. Khan, Safdar N. Fineberg, Steven J. Pelton, Miguel A. TI Clinical sequelae after rhBMP-2 use in a minimally invasive transforaminal lumbar interbody fusion SO SPINE JOURNAL LA English DT Article DE rhBMP-2; Neuroforaminal; Bone growth; MIS-TLIF; Pseudarthrosis ID BONE MORPHOGENETIC PROTEIN-2; SPINAL-FUSION; METAANALYSIS; SAFETY; CAGES AB BACKGROUND CONTEXT: Recent reports of postoperative radiculitis, bone osteolysis, and symptomatic ectopic bone formation after recombinant human bone morphogenetic protein-2 (rhBMP-2) use in transforaminal lumbar interbody fusions (TLIFs) are a cause for concern. PURPOSE: To determine the clinical and radiographic complications associated with BMP utilization in a minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) environment. STUDY DESIGN/SETTING: Retrospective clinical case series at a single institution. PATIENT SAMPLE: Five hundred seventy-three consecutive patients undergoing an MIS-TLIF. OUTCOME MEASURES: Reoperation rates and total costs associated with complications of rhBMP-2 use and pseudarthrosis. METHODS: A retrospective review of 610 consecutive patients undergoing an MIS-TLIF (2007-2010) by a single surgeon at our institution was performed (mean age 48.7 years, range 26-82 years). All patients underwent an MIS laminectomy with bilateral facetectomy, single TLIF cage, unilateral pedicle screw fixation, and 12 mg (large kit) or 4.2 mg (small kit) of rhBMP-2. The BMP-2 collagen-soaked sponge was placed anteriorly in the disc space, followed by local bone graft, and then the cage was filled only with local bone and no BMP-2. Patients were evaluated at 6 months and 1 year with computed tomography (CT) scan. Those demonstrating neuroforaminal bone growth, osteolysis/cage migration, or pseudarthrosis were reviewed, and cost data including direct cost/procedure for both index and revision surgeries were collected. RESULTS: Of the 573 patients, 10 (1.7%) underwent 15 additional procedures based on recalcitrant radiculopathy and CT evidence of neuroforaminal bone growth, vertebral body osteolysis, and/or cage migration. Thirty-nine patients (6.8%) underwent reoperation for clinically symptomatic pseudarthrosis. Bone overgrowth was associated with nerve impingement and radiculopathy in all 10 patients (small kit, n=9; large kit, n=1). Osteolysis and cage migration occurred in 2 (20%) of these same 10 patients. Average total costs were calculated per procedure ($19,224), and the costs for reoperation equaled $14,785 per encounter for neuroforaminal bone growth and $20,267 for pseudarthrosis. CONCLUSIONS: Symptomatic ectopic bone formation, vertebral osteolysis, and pseudarthrosis are recognized complications with the use of rhBMP-2 in MIS-TLIFs. Potential causes include improper dosage and a closed space that prevents the egress of the postoperative BMP-2 fluid collection. Management of these complications has a substantial cost for the patient and the surgeon and needs to be considered with the off-label use of rhBMP-2. (C) 2013 Elsevier Inc. All rights reserved. C1 [Singh, Kern; Nandyala, Sreeharsha V.; Marquez-Lara, Alejandro; Fineberg, Steven J.; Pelton, Miguel A.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Cha, Thomas D.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Khan, Safdar N.] Ohio State Univ, Wexner Med Ctr, Dept Orthopaed Surg, Columbus, OH 43203 USA. RP Singh, K (reprint author), Rush Univ, Med Ctr, Dept Orthopaed Surg, 1611 W Harrison St,Suite 400, Chicago, IL 60612 USA. EM kernsingh@hotmail.com RI Khan, Safdar/I-3108-2014 NR 18 TC 13 Z9 13 U1 7 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 J9 SPINE J JI Spine Journal PD SEP PY 2013 VL 13 IS 9 BP 1118 EP 1125 DI 10.1016/j.spinee.2013.07.028 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 216ZT UT WOS:000324326700019 PM 24029138 ER PT J AU Ferrone, CR AF Ferrone, Cristina R. TI Survival calculations Response SO SURGERY LA English DT Letter C1 Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. EM cferrone@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 2013 VL 154 IS 3 BP 645 EP 645 DI 10.1016/j.surg.2013.05.010 PG 1 WC Surgery SC Surgery GA 213UM UT WOS:000324085900031 PM 23972660 ER PT J AU Al-Marrawi, MY Rini, BI Harshman, LC Bjarnason, G Wood, L Vaishampayan, U MacKenzie, M Knox, JJ Agarwal, N Al-Harbi, H Kollmannsberger, C Tan, MH Rha, SY Donskov, FN North, S Choueiri, TK Heng, DY AF Al-Marrawi, Mhd Y. Rini, Brian I. Harshman, Lauren C. Bjarnason, Georg Wood, Lori Vaishampayan, Ulka MacKenzie, Mary Knox, Jennifer J. Agarwal, Neeraj Al-Harbi, Hulayel Kollmannsberger, Christian Tan, Min-Han Rha, Sun Young Donskov, Frede N. North, Scott Choueiri, Toni K. Heng, Daniel Y. CA Int mRCC Database Consortium TI The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients SO TARGETED ONCOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of American-Society-of-Clinical-Oncology (ASCO) CY JUN 01-08, 2011 CL Chicago, IL SP Amer Soc Clin Oncol DE Association of TKIs; First-line and second-line VEGF inhibitors; Renal cell cancer; Tyrosine kinase inhibitors; VEGF-targeted therapy ID PHASE-III TRIAL; PROGNOSTIC-FACTORS; INTERFERON-ALPHA; SORAFENIB; EVEROLIMUS; SUNITINIB; PAZOPANIB; SURVIVAL; EFFICACY; CANCER AB There are many active drugs to treat metastatic renal cell carcinoma (mRCC) patients who progress through their first-line vascular endothelial growth factor (VEGF) inhibitor. Many clinicians choose a second-line VEGF inhibitor based on the type of response to first-line VEGF inhibitor, without data supporting this practice. This study was conducted to determine the association of response to second-line VEGF inhibitor with response to first-line VEGF inhibitor. All mRCC patients in participating centers of the International mRCC Database Consortium who were treated from January 2004 through June 2011 with a second-line VEGF inhibitor after failure of a different first-line VEGF inhibitor were retrospectively identified. The primary outcome is objective response rate (ORR) and the secondary outcome is progression-free survival (PFS) in each line of therapy. Of 1,602 total database patients, 464 patients received a first- and second-line VEGF inhibitor. The ORR to first-line therapy was 22 %, and the ORR to second-line therapy was 11 %. The ORR to second-line therapy was not different among patients achieving partial response versus stable disease versus progressive disease to first-line therapy (14 % vs. 10 % vs. 11 %, respectively; chi-squared trend test p = 0.17). The median PFS on first-line VEGF-targeted therapy was 7.5 months (95 % CI, 6.6-8.1), and the median PFS on second-line VEGF inhibitor was 3.9 months (95 % CI, 3.6-4.5). There was no correlation between first-line and second-line PFS (Pearson correlation coefficient 0.025; p = 0.59). The clinical response to a second-line VEGF inhibitor is not dependent on response to the first-line VEGF-inhibitor. Further studies are needed to define clinical parameters that predict response to second-line therapy to optimize the sequence of VEGF-targeted therapy in metastatic RCC patients. C1 [Al-Marrawi, Mhd Y.; Rini, Brian I.] Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA. [Harshman, Lauren C.; Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. [Bjarnason, Georg] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Vaishampayan, Ulka] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [MacKenzie, Mary] London Hlth Sci Ctr, London, ON, Canada. [Knox, Jennifer J.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Agarwal, Neeraj] Univ Utah, Div Med Oncol, Huntsman Canc Inst, Salt Lake City, UT USA. [Al-Harbi, Hulayel] Univ Calgary, Calgary, AB T2N 4N2, Canada. [Kollmannsberger, Christian] British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. [Tan, Min-Han] Natl Canc Ctr Singapore, Inst Bioengn & Nanotechnol, Singapore, Singapore. [Rha, Sun Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. [Donskov, Frede N.] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [North, Scott] Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. [Heng, Daniel Y.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada. RP Heng, DY (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU NCI NIH HHS [P30 CA022453] NR 19 TC 23 Z9 23 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 J9 TARGET ONCOL JI Target. Oncol. PD SEP PY 2013 VL 8 IS 3 BP 203 EP 209 DI 10.1007/s11523-012-0252-7 PG 7 WC Oncology SC Oncology GA 214FF UT WOS:000324116000006 PM 23300029 ER PT J AU Deatrick, KB Obi, A Luke, CE Elfline, MA Sood, V Upchurch, GR Jaffer, F Wakefield, TW Henke, PK AF Deatrick, Kristopher B. Obi, Andrea Luke, Catherine E. Elfline, Megan A. Sood, Vikram Upchurch, Gilbert R., Jr. Jaffer, Farouc Wakefield, Thomas W. Henke, Peter K. TI Matrix metalloproteinase-9 deletion is associated with decreased mid-term vein wall fibrosis in experimental stasis DVT SO THROMBOSIS RESEARCH LA English DT Article DE Venous thrombosis; Inflammation; Matrix metalloproteinases; Monocytes ID VENOUS THROMBOSIS RESOLUTION; MOLECULAR-WEIGHT HEPARIN; MUSCLE-CELL MIGRATION; MATRIX METALLOPROTEINASES; MOUSE MODEL; TISSUE INHIBITORS; INFLAMMATION; COLLAGEN; INJURY; POLARIZATION AB Introduction: Post thrombotic syndrome therapy is primarily palliative, and the associated vein wall inflammatory mechanisms are unclear. Vein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP9 directly contributes to vein wall remodeling after VT is unknown. Methods: WT and MMP9-/- mice underwent stasis VT by ligation of the inferior vena cava (IVC) and tissue was harvested at 2, 8, and 21 days. Assessment of thrombus size, and gene, protein and structural vein wall determinations were done. Results: VT resolution was increased in MMP9-/- mice as compared with controls at 21d only. The primary phenotypic fibrotic vein wall differences occurred at 8d post VT, with significantly less vein wall collagen content as assessed by Picosirius red staining in MMP9-/- mice as compared with WT. Increased monocytic vein wall influx with less IL-1b and TGFb was found in MMP9-/- vein walls as compared with WT. Corresponding levels of PAI-1 were increased in MMP9-/- compared with WT, and no difference in FSP-1 + cells as compared with controls. Conclusions: In stasis VT, MMP9 modulates midterm vein wall collagen content, with an altered local inflammatory and profibrotic environment, likely directed by monocytes. Thus, MMP9 plays a role in both vein wall responses as well as late thrombus resolution. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Deatrick, Kristopher B.; Obi, Andrea; Luke, Catherine E.; Elfline, Megan A.; Sood, Vikram; Upchurch, Gilbert R., Jr.; Wakefield, Thomas W.; Henke, Peter K.] Univ Michigan, Conrad Jobst Vasc Res Lab, Vasc Surg Sect, Sch Med,Dept Surg, Boston, MA USA. [Jaffer, Farouc] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Jaffer, Farouc] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Henke, PK (reprint author), Univ Michigan Hlth Syst, Cardiovasc Ctr 5463, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM henke@umich.edu OI Obi, Andrea/0000-0001-7613-2366 FU [HL083918]; [HL092129]; [T32HL092129] FX Supported by: HL083918 and HL092129 (PKH), and T32HL092129 (TW). NR 38 TC 12 Z9 16 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD SEP PY 2013 VL 132 IS 3 BP 360 EP 366 DI 10.1016/j.thromres.2013.06.027 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 213MD UT WOS:000324060400011 PM 23978304 ER PT J AU Sieber, J Weins, A Kampe, K Gruber, S Lindenmeyer, MT Cohen, CD Orellana, JM Mundel, P Jehle, AW AF Sieber, Jonas Weins, Astrid Kampe, Kapil Gruber, Stefan Lindenmeyer, Maja T. Cohen, Clemens D. Orellana, Jana M. Mundel, Peter Jehle, Andreas W. TI Susceptibility of Podocytes to Palmitic Acid Is Regulated by Stearoyl-CoA Desaturases 1 and 2 SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INDUCED GENE-EXPRESSION; INSULIN-RESISTANCE; DIABETIC-NEPHROPATHY; DIACYLGLYCEROL ACYLTRANSFERASE; 3T3-L1 PREADIPOCYTES; FATTY-ACIDS; MICE; LIVER; OBESITY; IDENTIFICATION AB Type 2 diabetes mellitus is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are highly susceptible to saturated FFAs but not to protective, monounsaturated FFAs. We report that patients with diabetic nephropathy develop alterations in glomerular gene expression of enzymes involved in fatty acid metabolism, including induction of stearoyl-CoA desaturase (SCD)-1, which converts saturated to monounsaturated FFAs. By IHC of human renal biopsy specimens, glomerular SCD-1 induction was observed in podocytes of patients with diabetic nephropathy. Functionally, the liver X receptor agonists T0901317 and GW3965, two known inducers of SCD, increased Scd-1 and Scd-2 expression in cultured podocytes and reduced palmitic acid-induced cell death. Similarly, overexpression of Scd-1 attenuated palmitic acid-induced cell death. The protective effect of T0901317 was associated with a reduction of endoplasmic reticulum stress. It was lost after gene silencing of Scd-1/-2, thereby confirming that the protective effect of T0901317 is mediated by Scd-1/-2. T0901317 also shifted palmitic acid-derived FFAs into biologically inactive triglycerides. In summary, SCD-1 up-regulation in diabetic nephropathy may be part of a protective mechanism against saturated FFA-derived toxic metabolites that drive endoplasmic reticulum stress and podocyte death. C1 [Sieber, Jonas; Kampe, Kapil; Orellana, Jana M.; Jehle, Andreas W.] Univ Basel Hosp, Lab Mol Nephrol, Dept Biomed, CH-4031 Basel, Switzerland. [Jehle, Andreas W.] Univ Basel Hosp, Dept Internal Med Transplantat Immunol & Nephrol, CH-4031 Basel, Switzerland. [Sieber, Jonas; Weins, Astrid; Mundel, Peter; Jehle, Andreas W.] Harvard Univ, Sch Med, Boston, MA USA. [Sieber, Jonas; Weins, Astrid; Mundel, Peter; Jehle, Andreas W.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Weins, Astrid] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gruber, Stefan] Univ Basel, Kantonsspital Bruderholz, Dept Chem, Basel, Switzerland. [Jehle, Andreas W.] Univ Basel, Kantonsspital Bruderholz, Dept Internal Med, Basel, Switzerland. [Lindenmeyer, Maja T.; Cohen, Clemens D.] Univ Zurich, Inst Physiol, Zurich, Switzerland. [Lindenmeyer, Maja T.; Cohen, Clemens D.] Univ Zurich Hosp, Div Nephrol, CH-8091 Zurich, Switzerland. RP Jehle, AW (reprint author), Univ Basel Hosp, Dept Biomed Mol Nephrol, Room 303,Hebelstr 20, CH-4031 Basel, Switzerland. EM andreas.jehle@unibas.ch FU Swiss National Science Foundation [31003A-119974, 31003A-144112/1]; Novartis Foundation for Medical Biological Research [10C57]; Swiss National Science Foundation Fellowship [PBBSP3-144160]; National Institutes Health [DK62472, DK57683]; NIH/N IDDK [K08 DK0933783-01]; Else-Kroner-Fresenius Foundation FX Supported by Swiss National Science Foundation grants 31003A-119974 and 31003A-144112/1 (A.W.J.), Novartis Foundation for Medical Biological Research 10C57 (A.W.J.), Swiss National Science Foundation Fellowship PBBSP3-144160 (J.S.), and National Institutes Health Grants DK62472 and DK57683 (P.M.), NIH/N IDDK K08 DK0933783-01 (A.W.), and the Else-Kroner-Fresenius Foundation (C.D.C.). NR 45 TC 9 Z9 11 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2013 VL 183 IS 3 BP 735 EP 744 DI 10.1016/j.ajpath.2013.05.023 PG 10 WC Pathology SC Pathology GA 210WP UT WOS:000323866000010 PM 23867797 ER PT J AU Krautkramer, KA Linnemann, AK Fontaine, DA Whillock, AL Harris, TW Schleis, GJ Truchan, NA Marty-Santos, L Lavine, JA Cleaver, O Kimple, ME Davis, DB AF Krautkramer, Kimberly A. Linnemann, Amelia K. Fontaine, Danielle A. Whillock, Amy L. Harris, Ted W. Schleis, Gregory J. Truchan, Nathan A. Marty-Santos, Leilani Lavine, Jeremy A. Cleaver, Ondine Kimple, Michelle E. Davis, Dawn Belt TI Tcf19 is a novel islet factor necessary for proliferation and survival in the INS-1 beta-cell line SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE diabetes; beta-cell; islet; proliferation; apoptosis; transcription factor 19; transcription; endoplasmic reticulum stress ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; DIABETES-MELLITUS; ER STRESS; MISFOLDED GLYCOPROTEINS; DEVELOPING PANCREAS; FHA DOMAIN; EXPRESSION; APOPTOSIS; MASS AB Recently, a novel type 1 diabetes association locus was identified at human chromosome 6p31.3, and transcription factor 19 (TCF19) is a likely causal gene. Little is known about Tcf19, and we now show that it plays a role in both proliferation and apoptosis in insulinoma cells. Tcf19 is expressed in mouse and human islets, with increasing mRNA expression in nondiabetic obesity. The expression of Tcf19 is correlated with beta-cell mass expansion, suggesting that it may be a transcriptional regulator of beta-cell mass. Increasing proliferation and decreasing apoptotic cell death are two strategies to increase pancreatic beta-cell mass and prevent or delay diabetes. siRNA-mediated knockdown of Tcf19 in the INS-1 insulinoma cell line, a beta-cell model, results in a decrease in proliferation and an increase in apoptosis. There was a significant reduction in the expression of numerous cell cycle genes from the late G1 phase through the M phase, and cells were arrested at the G1/S checkpoint. We also observed increased apoptosis and susceptibility to endoplasmic reticulum (ER) stress after Tcf19 knockdown. There was a reduction in expression of genes important for the maintenance of ER homeostasis (Bip, p58(IPK), Edem1, and calreticulin) and an increase in proapoptotic genes (Bim, Bid, Nix, Gadd34, and Pdia2). Therefore, Tcf19 is necessary for both proliferation and survival and is a novel regulator of these pathways. C1 [Krautkramer, Kimberly A.; Linnemann, Amelia K.; Fontaine, Danielle A.; Whillock, Amy L.; Harris, Ted W.; Schleis, Gregory J.; Truchan, Nathan A.; Kimple, Michelle E.; Davis, Dawn Belt] Univ Wisconsin, Dept Med, Div Endocrinol Diabet & Metab, Madison, WI USA. [Lavine, Jeremy A.; Davis, Dawn Belt] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Marty-Santos, Leilani; Cleaver, Ondine] Univ Texas Southwestern, Dept Mol Biol, Dallas, TX USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Davis, DB (reprint author), 4148 MFCB,MC 5148,1685 Highland Ave, Madison, WI 53705 USA. EM dbd@medicine.wisc.edu RI Davis, Dawn/B-1624-2013; OI Cleaver, Ondine/0000-0003-2454-6641 FU NIDDK [K08-DK-083442, 3R01-DK-079862-S1, F31-DK-092098, 5-R01-DK-079862]; William and Judith Busse Women in Research Foundation; University of Wisconsin School of Medicine and Public Health and Department of Medicine, Division of Endocrinology; Wisconsin Alumni Research Foundation; Central Society for Clinical Research; Pilot Award from the Integrated Islet Distribution Program; JDRF [17-2011-608]; Medical Scientist Training Program [T32GM08692]; National Center for Advancing Translational Sciences [UL1TR0000427] FX D. B. Davis acknowledges research support from the NIDDK (K08-DK-083442), the William and Judith Busse Women in Research Foundation, the University of Wisconsin School of Medicine and Public Health and Department of Medicine, Division of Endocrinology, the Wisconsin Alumni Research Foundation, and the Central Society for Clinical Research. D. B. Davis was also the recipient of a Pilot Award from the Integrated Islet Distribution Program that provided an allotment of human islets. M. E. Kimple has received research support from JDRF (17-2011-608). J. A. Lavine and K. A. Krautkramer have been supported by the Medical Scientist Training Program (T32GM08692). O. Cleaver and L. Marty-Santos have also been supported by the NIDDK [3R01-DK-079862-S1 (L. Marty-Santos), F31-DK-092098 (L. Marty-Santos), and 5-R01-DK-079862 (O. Cleaver)]. We also acknowledge statistical consultation through the Clinical and Translational Science Award program through National Center for Advancing Translational Sciences Grant UL1TR0000427. NR 55 TC 5 Z9 5 U1 3 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2013 VL 305 IS 5 BP E600 EP E610 DI 10.1152/ajpendo.00147.2013 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 211WH UT WOS:000323941900004 PM 23860123 ER PT J AU Mitchell, T Johnson, MS Ouyang, XS Chacko, BK Mitra, K Lei, XY Gai, Y Moore, DR Barnes, S Zhang, JH Koizumi, A Ramanadham, S Darley-Usmar, VM AF Mitchell, Tanecia Johnson, Michelle S. Ouyang, Xiaosen Chacko, Balu K. Mitra, Kasturi Lei, Xiaoyong Gai, Ying Moore, D. Ray Barnes, Stephen Zhang, Jianhua Koizumi, Akio Ramanadham, Sasanka Darley-Usmar, Victor M. TI Dysfunctional mitochondrial bioenergetics and oxidative stress in Akita(+/Ins2)-derived beta-cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE diabetes mellitus; beta-cell; mitochondrial respiration; endoplasmic reticulum stress; mitochondrial quality control ID ENDOPLASMIC-RETICULUM STRESS; DIABETES-MELLITUS; INSULIN GENE; SUPEROXIDE-DISMUTASE; MUTANT MICE; AUTOPHAGY; MUTATIONS; EXPRESSION; MECHANISM; MOUSE AB Insulin release from pancreatic beta-cells plays a critical role in blood glucose homeostasis, and beta-cell dysfunction leads to the development of diabetes mellitus. In cases of monogenic type 1 diabetes mellitus (T1DM) that involve mutations in the insulin gene, we hypothesized that misfolding of insulin could result in endoplasmic reticulum (ER) stress, oxidant production, and mitochondrial damage. To address this, we used the Akita(+/Ins2) T1DM model in which misfolding of the insulin 2 gene leads to ER stress-mediated beta-cell death and thapsigargin to induce ER stress in two different beta-cell lines and in intact mouse islets. Using transformed pancreatic beta-cell lines generated from wild-type Ins2(-/-) (WT) and Akita(+/Ins2) mice, we evaluated cellular bioenergetics, oxidative stress, mitochondrial protein levels, and autophagic flux to determine whether changes in these processes contribute to beta-cell dysfunction. In addition, we induced ER stress pharmacologically using thapsigargin in WT beta-cells, INS-1 cells, and intact mouse islets to examine the effects of ER stress on mitochondrial function. Our data reveal that Akita(+/Ins2)-derived beta-cells have increased mitochondrial dysfunction, oxidant production, mtDNA damage, and alterations in mitochondrial protein levels that are not corrected by autophagy. Together, these findings suggest that deterioration in mitochondrial function due to an oxidative environment and ER stress contributes to beta-cell dysfunction and could contribute to T1DM in which mutations in insulin occur. C1 [Mitchell, Tanecia; Johnson, Michelle S.; Ouyang, Xiaosen; Chacko, Balu K.; Zhang, Jianhua; Darley-Usmar, Victor M.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Mitchell, Tanecia; Johnson, Michelle S.; Ouyang, Xiaosen; Chacko, Balu K.; Barnes, Stephen; Zhang, Jianhua; Darley-Usmar, Victor M.] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Mitra, Kasturi] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Lei, Xiaoyong; Gai, Ying; Ramanadham, Sasanka] Univ Alabama Birmingham, Dept Cell, Birmingham, AL 35294 USA. [Barnes, Stephen] Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Moore, D. Ray; Barnes, Stephen] Univ Alabama Birmingham, Targeted Metabol & Prote Lab, Birmingham, AL 35294 USA. [Koizumi, Akio] Kyoto Grad Sch Med, Dept Hlth & Environm Sci, Kyoto, Japan. RP Darley-Usmar, VM (reprint author), Univ Alabama Birmingham, Dept Pathol, Biomed Res Bldg 2,901 19th St South, Birmingham, AL 35294 USA. EM darley@uab.edu FU Veterans Affairs Merit Award [AA-13395, DK-075865]; O'Brien Center [P30-DK-079337]; University of Alabama at Birmingham Health Services Foundation General Endowment Fund; [T32-DK-007545]; [DK-69455]; [NS-064090] FX We appreciate support from the following: T32-DK-007545 (T. Mitchell), DK-69455 (S. Ramanadham), NS-064090 and a Veterans Affairs Merit Award (J. Zhang), AA-13395 and DK-075865 (V. M. Darley-Usmar), and the O'Brien Center P30-DK-079337 (S. Barnes and V. M. Darley-Usmar). Funds for the mass spectrometer used in this study were provided by a grant from the University of Alabama at Birmingham Health Services Foundation General Endowment Fund. NR 62 TC 15 Z9 16 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2013 VL 305 IS 5 BP E585 EP E599 DI 10.1152/ajpendo.00093.2013 PG 15 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 211WH UT WOS:000323941900003 PM 23820623 ER PT J AU Rudders, SA Clark, S Wei, WH Camargo, CA AF Rudders, Susan A. Clark, Sunday Wei, Wenhui Camargo, Carlos A., Jr. TI Longitudinal study of 954 patients with stinging insect anaphylaxis SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID EMERGENCY-DEPARTMENT; VENOM HYPERSENSITIVITY; ALLERGY; CHILDREN; IMMUNOTHERAPY; EPINEPHRINE; MANAGEMENT; EPIDEMIOLOGY; PREVALENCE; SEVERITY AB Background: Stinging insect anaphylaxis (SIA) is a common cause of anaphylaxis and is potentially life-threatening. Objectives: To examine US patients with an emergency department (ED) visit or hospitalization for SIA to evaluate postdischarge follow-up care. Methods: We identified all patients with an ED visit or hospitalization for SIA during 2002-2008 in the MarketScan Database using International Classification of Diseases, Ninth Revision, Clinical Modification codes (index date was the initial ED visit or hospitalization). Patients were required to have continuous full insurance coverage for 1 year or more before and after index. We examined patient factors during the preindex period, characteristics of the index event, and outcomes during the postindex period. Multivariable logistic regression was used to identify independent predictors of receiving preventive anaphylaxis care. Results: We identified 954 patients with an ED visit or hospitalization for SIA (mean [SD] age, 46 [19] years; 41% female). A total of 85% of patients were discharged directly from the ED. For those hospitalized, the mean hospital stay was 1 day, and 50% spent time in the intensive care unit. Cardiorespiratory failure occurred in 27% of those hospitalized. During the postindex period, 69% filled 1 or more epinephrine autoinjector prescription, but only 14% had 1 or more allergist/immunologist visit. Independent factors associated with receiving preventive anaphylaxis care during the postindex period were higher household income, no ED visit (for any reason) in the preindex period, and no cardiorespiratory arrest or failure during the index event. Conclusion: Although two-thirds of patients filled a prescription for an epinephrine autoinjector after an ED visit or hospitalization for SIA, only 14% of patients received follow-up care by an allergist/immunologist. This missed opportunity to provide venom immunotherapy, an essentially curative therapy, unnecessarily places patients at risk for recurrent anaphylaxis. (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Rudders, Susan A.] Brown Univ, Rhode Isl Hosp, Dept Pediat, Div Asthma & Allergy,Alpert Sch Med, Providence, RI 02903 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Wei, Wenhui] Sanofi US, Bridgewater, NJ USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Rudders, SA (reprint author), Rhode Isl Hosp, Dept Pediat, 593 Eddy St, Providence, RI 02903 USA. EM srudders@lifespan.org FU Sanofi US FX This study was funded by Sanofi US. NR 32 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD SEP PY 2013 VL 111 IS 3 BP 199 EP U121 DI 10.1016/j.anai.2013.06.020 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 211VM UT WOS:000323939400012 PM 23987196 ER PT J AU Nan, HM Lee, JE Rimm, EB Fuchs, CS Giovannucci, EL Cho, E AF Nan, Hongmei Lee, Jung Eun Rimm, Eric B. Fuchs, Charles S. Giovannucci, Edward L. Cho, Eunyoung TI Prospective study of alcohol consumption and the risk of colorectal cancer before and after folic acid fortification in the United States SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Folic acid fortification; Alcohol consumption; Colorectal cancer ID DOSE-RESPONSE METAANALYSIS; ONE-CARBON METABOLISM; COLON-CANCER; FAMILY-HISTORY; FOLATE METABOLISM; MULTIVITAMIN USE; DNA METHYLATION; NURSES HEALTH; LIFE-STYLE; WOMEN AB Purpose: To evaluate the influence of alcohol consumption on the risk of colorectal cancer according to folic acid fortification period in the United States. Methods: We evaluated the association between alcohol consumption and colorectal cancer by fortification period (before 1998 vs. after 1998) in 2 prospective cohort studies, the Nurses' Health Study (NHS) of women and the Health Professionals Follow-up Study (HPFS) of men, in which 2793 cases of invasive colorectal cancer were documented. Results: Alcohol consumption was associated with an increased risk of colorectal cancer. Among nonusers of multivitamins and/or folic acid supplements, the pooled multivariate relative risk for >= 30 g/d drinkers versus nondrinkers was 1.36 (95% confidence interval [95% CI], 1.09-1.70; P for trend, 0.02). The effect of alcohol consumption was slightly stronger in the prefolic acid fortification period (1980 NHS/1986 HPFS-1998) than in the postfortification period (1998-2008); the pooled multivariate relative risks for >= 30 g/d drinkers versus nondrinkers were 1.31 (95% CI, 1.00-1.71; P for trend, 0.10) in the prefortification period and 1.07 (95% CI, 0.69-1.65; P for trend, 0.67) in the postfortification period. Conclusions: Folic acid fortification may attenuate the adverse effect of high alcohol consumption on the risk of colorectal cancer. (c) 2013 Elsevier Inc. All rights reserved. C1 [Nan, Hongmei] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Div Canc Epidemiol, Baltimore, MD 21201 USA. [Nan, Hongmei; Rimm, Eric B.; Fuchs, Charles S.; Giovannucci, Edward L.; Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Nan, Hongmei; Rimm, Eric B.; Fuchs, Charles S.; Giovannucci, Edward L.; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Rimm, Eric B.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rimm, Eric B.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cho, E (reprint author), Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu OI Lee, Jung Eun/0000-0003-1141-878X FU National Institutes of Health [AA017693, CA87969, CA55075] FX This work was supported by research grants AA017693, CA87969 and CA55075 from the National Institutes of Health. All authors participated in the design of the study, interpretation of the data, and writing of the manuscript. None of the authors had any personal or financial conflicts of interest. We thank the participants and staff of the Nurses' Health Study and Health Professionals Follow-Up Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. NR 52 TC 7 Z9 9 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2013 VL 23 IS 9 BP 558 EP 563 DI 10.1016/j.annepidem.2013.04.011 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 210TE UT WOS:000323856700006 PM 23726821 ER PT J AU Goldhirsch, A Winer, EP Coates, AS Gelber, RD Piccart-Gebhart, M Thurlimann, B Senn, HJ AF Goldhirsch, A. Winer, E. P. Coates, A. S. Gelber, R. D. Piccart-Gebhart, M. Thuerlimann, B. Senn, H. -J. CA Panel Members TI Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 SO ANNALS OF ONCOLOGY LA English DT Article DE surgery; radiation therapy; systemic adjuvant therapies; early breast cancer; St Gallen Consensus; subtypes ID RECURRENCE SCORE ASSAY; ADJUVANT ENDOCRINE THERAPY; NO AXILLARY DISSECTION; BODY-MASS INDEX; GENE-EXPRESSION PROFILES; RANDOMIZED PHASE-3 TRIAL; POSTMENOPAUSAL WOMEN; PROGNOSTIC-FACTORS; COST-EFFECTIVENESS; PREDICTIVE-VALUE AB The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and 'triple-negative' disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints. C1 [Goldhirsch, A.] Int Breast Canc Study Grp, European Inst Oncol, Div Med Oncol, I-20141 Milan, Italy. [Winer, E. P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Coates, A. S.] Int Breast Canc Study Grp, Sydney, NSW, Australia. [Coates, A. S.] Univ Sydney, Sydney, NSW 2006, Australia. [Gelber, R. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Int Breast Canc Study Grp,Stat Ctr,Dept Biostat &, Boston, MA 02115 USA. [Piccart-Gebhart, M.] Inst Jules Bordet, B-1000 Brussels, Belgium. [Thuerlimann, B.] Kantonsspital St Gallen, Breast Ctr, St Gallen, Switzerland. [Senn, H. -J.] Tumor & Breast Ctr ZeTuP, St Gallen, Switzerland. RP Goldhirsch, A (reprint author), Int Breast Canc Study Grp, European Inst Oncol, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org RI Goodwin, Pamela/K-1477-2013; OI Semiglazov, Vladimir/0000-0003-0077-9619; Sedlmayer, Felix/0000-0002-1181-0178; Gnant, Michael/0000-0003-1002-2118; Cardoso, Fatima/0000-0002-6692-2249 FU SONK; United States National Cancer Institute (IBCSG Statistical Center) [CA75362] FX Support for the conference was provided by SONK from registration fees paid by the conference attendees and by Grant No. CA75362 from the United States National Cancer Institute (IBCSG Statistical Center, R. Gelber, PI). NR 119 TC 694 Z9 772 U1 11 U2 155 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2013 VL 24 IS 9 BP 2206 EP 2223 DI 10.1093/annonc/mdt303 PG 18 WC Oncology SC Oncology GA 212DT UT WOS:000323963100003 PM 23917950 ER PT J AU Turner, NH Partridge, A Sanna, G Di Leo, A Biganzoli, L AF Turner, N. H. Partridge, A. Sanna, G. Di Leo, A. Biganzoli, L. TI Utility of gonadotropin-releasing hormone agonists for fertility preservation in young breast cancer patients: the benefit remains uncertain SO ANNALS OF ONCOLOGY LA English DT Review DE breast cancer; chemotherapy; fertility; GNRH analogue; young age ID ANTI-MULLERIAN HORMONE; PREMATURE OVARIAN FAILURE; PREMENOPAUSAL WOMEN; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; GENE-EXPRESSION; INHIBIN-B; EMBRYO CRYOPRESERVATION; FOLLICULAR STATUS; FEMALE RATS AB Breast cancer in young women is typically characterised by aggressive disease, and treatment with adjuvant chemotherapy is generally recommended. Chemotherapy has conferred significant improvements in disease-free and overall survival for young women with breast cancer; however, with improved cure rates, long-term adverse effects of cytotoxic treatment, such as premature ovarian failure (POF) and infertility, have become increasingly important. A potential fertility preservation strategy is administration of gonadotropin-releasing hormone agonists (GnRHas) during adjuvant chemotherapy. This review analyses and summarises the current evidence for use of GnRHa in preserving ovarian function in young breast cancer patients. Twelve trials, both non-randomised and randomised, have now been conducted assessing GnRHas in fertility preservation in young breast cancer patients, with conflicting results. Limitations of the current data include the use of poorly sensitive end points for fertility preservation, variable age of enrolled patients and limited pregnancy data. The utility of GnRHa as a fertility preservation strategy remains uncertain, and use outside of a clinical trial generally not recommended. Further research into this under-recognised issue is vital. C1 [Turner, N. H.; Sanna, G.; Di Leo, A.; Biganzoli, L.] Hosp Prato, Sandro Pitigliani Med Oncol Dept, Ist Toscano Tumori, I-59100 Prato, Italy. [Partridge, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Partridge, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Biganzoli, L (reprint author), Hosp Prato, Sandro Pitigliani Med Oncol Dept, Piazza Osped 2, I-59100 Prato, Italy. EM lbiganzoli@usl4.toscana.it OI Rainey, Natalie/0000-0002-2016-5051 NR 76 TC 39 Z9 41 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2013 VL 24 IS 9 BP 2224 EP 2235 DI 10.1093/annonc/mdt196 PG 12 WC Oncology SC Oncology GA 212DT UT WOS:000323963100004 PM 23709175 ER PT J AU Melichar, B Bracarda, S Matveev, V Alekseev, B Ivanov, S Zyryanov, A Janciauskiene, R Fernebro, E Mulders, P Osborne, S Jethwa, S Mickisch, G Gore, M van Moorselaar, RJA Staehler, M Magne, N Bellmunt, J AF Melichar, B. Bracarda, S. Matveev, V. Alekseev, B. Ivanov, S. Zyryanov, A. Janciauskiene, R. Fernebro, E. Mulders, P. Osborne, S. Jethwa, S. Mickisch, G. Gore, M. van Moorselaar, R. J. A. Staehler, M. Magne, N. Bellmunt, J. CA BEVLIN Investigators TI A multinational phase II trial of bevacizumab with low-dose interferon-alpha 2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN SO ANNALS OF ONCOLOGY LA English DT Article DE renal cell carcinoma; angiogenesis; bevacizumab; immunotherapy; interferon; VEGF ID PLUS INTERFERON-ALPHA-2A; CANCER-PATIENTS; ALPHA; TEMSIROLIMUS; SUNITINIB; SURVIVAL AB Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-alpha 2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity. BEVLiN was an open-label, single-arm, multinational, phase II trial. Nephrectomized patients with treatment-naive, clear cell mRCC and favourable/intermediate Memorial Sloan-Kettering Cancer Center scores received bevacizumab (10 mg/kg every 2 weeks) and IFN (3 MIU thrice weekly) until disease progression. Descriptive comparisons with AVOREN patients having favourable/intermediate MSKCC scores treated with bevacizumab plus IFN (9 MIU) were made. Primary end points were grade >= 3 IFN-associated adverse events (AEs) and progression-free survival (PFS). All grade >= 3 AEs and bevacizumab/IFN-related grade 1-2 AEs occurring from first administration until 28 days after last treatment were reported. A total of 146 patients were treated; the median follow-up was 29.4 months. Any-grade and grade >= 3 IFN-associated AEs occurred in 53.4% and 10.3% of patients, respectively. The median PFS and overall survival were 15.3 [95% confidence interval (CI): 11.7-18.0] and 30.7 months (95% CI: 25.7-not reached), respectively. The ORR was 28.8%. Compared with a historical control AVOREN subgroup, low-dose IFN with bevacizumab resulted in a reduction in incidence rates of IFN-related AEs, without compromising efficacy [NCT00796757]. C1 [Melichar, B.] Palacky Univ, Sch Med, Dept Oncol, Olomouc 77520, Czech Republic. [Melichar, B.] Teaching Hosp, Olomouc, Czech Republic. [Bracarda, S.] Osped San Donato, Dept Oncol, Arezzo, Italy. [Matveev, V.] NN Blokhin Canc Res Ctr, Moscow, Russia. [Alekseev, B.] Oncol Res Inst, Moscow, Russia. [Ivanov, S.] Russian Res Ctr Roentgenoradiol, Dept Chemotherapy, Moscow, Russia. [Zyryanov, A.] Reg Hosp 1 Oncol, Ekaterinburg, Russia. [Janciauskiene, R.] Lithuanian Univ Hlth Sci, Inst Oncol, Kaunas, Lithuania. [Fernebro, E.] Vaxjo Hosp, Dept Oncol, Vaxjo, Sweden. [Mulders, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Osborne, S.] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Jethwa, S.] Ctr Operat Urol, Bremen, Germany. [Gore, M.] Royal Marsden, London, England. [van Moorselaar, R. J. A.] Vrije Univ Amsterdam, Med Ctr, Dept Urol, Amsterdam, Netherlands. [Staehler, M.] Klinikum Univ Munchen, Munich, Germany. [Magne, N.] Inst Cancerol Loire, Dept Radiotherapy, St Priest En Jarez, France. [Bellmunt, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellmunt, J.] Hosp del Mar, Med Oncol Serv, Barcelona, Spain. RP Melichar, B (reprint author), Palacky Univ, Sch Med, Dept Oncol, IP Pavlova 6, Olomouc 77520, Czech Republic. EM bohuslav.melichar@fnol.cz RI Mulders, Peter/H-8076-2014 FU F. Hoffmann-La Roche Ltd.; F. Hoffmann-La Roche Ltd, Basel, Switzerland FX This work was supported by F. Hoffmann-La Roche Ltd. The trial was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The study sponsor was involved in trial design, coordination of data collection, data analysis and interpretation, the writing of the report, and supplied bevacizumab. After data lock, the sponsor, investigators, and all authors had full access to the data. All authors gave their permission to submit for publication. NR 24 TC 11 Z9 13 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2013 VL 24 IS 9 BP 2396 EP 2402 DI 10.1093/annonc/mdt228 PG 7 WC Oncology SC Oncology GA 212DT UT WOS:000323963100030 PM 23803225 ER PT J AU Garcia-Donas, J Leandro-Garcia, LJ del Alba, AG Morente, M Alemany, I Esteban, E Arranz, JA Climent, MA Gallardo, E Castellano, DE Bellmunt, J Mellado, B Puente, J Moreno, F Font, A Hernando, S Robledo, M Rodriguez-Antona, C AF Garcia-Donas, J. Leandro-Garcia, L. J. del Alba, A. Gonzlez Morente, M. Alemany, I. Esteban, E. Arranz, J. A. Climent, M. A. Gallardo, E. Castellano, D. E. Bellmunt, J. Mellado, B. Puente, J. Moreno, F. Font, A. Hernando, S. Robledo, M. Rodriguez-Antona, C. TI Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE renal carcinoma; EGLN3; hypoxia; immunohistochemistry; predictive marker; sunitinib ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-TARGETED THERAPY; CARBONIC-ANHYDRASE-IX; LINDAU GENE STATUS; BIOMARKERS; PREDICTORS; VEGF; VHL AB Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs. Thus, we aimed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma (ccRCC). The expression of eight key proteins related to hypoxia (CAIX, HIF1A, HIF2A, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC samples from prospectively recruited patients treated with first-line sunitinib. The proteins expression, VHL inactivation and EGLN3 mRNA content were compared with the patients' response to sunitinib. High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response (P = 0.024 and P = 0.026; respectively) and increased VEGFR3 expression was associated with longer progression-free survival (P = 0.012). VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 (P = 0.002), a sunitinib resistance predictor. With respect to overall survival (OS), high VEGFA was associated with short (P = 0.009) and HIF2A with long (P = 0.048) survival times. High EGLN3 mRNA content was associated with shorter OS (P = 0.023). We found an association between several proteins involved in hypoxia and sunitinib efficacy. In addition, low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele, reinforcing VEGFR3 as a marker of sunitinib resistance. C1 [Garcia-Donas, J.] Ctr Integral Oncol Clara Campal, Genitourinary & Gynecol Tumors & Rare Canc Progra, Madrid, Spain. [Garcia-Donas, J.] Spanish Natl Canc Res Ctr CNIO, Prostate Canc & Genitourinary Tumors Clin Res Uni, Madrid, Spain. [Robledo, M.; Rodriguez-Antona, C.] Spanish Natl Canc Res Ctr CNIO, Hereditary Endocrine Canc Grp, Human Canc Genet Programme, Madrid 28029, Spain. [del Alba, A. Gonzlez] Hosp Univ Son Espases, Dept Med Oncol, Palma de Mallorca, Spain. [del Alba, A. Gonzlez] Spanish Natl Canc Res Ctr, Tumour Bank Unit, Madrid, Spain. [Alemany, I.] Hosp Univ Fundacion Alcorcon, Anat Pathol Unit, Madrid, Spain. [Esteban, E.] Hosp Univ Cent Asturias, Dept Med Oncol, Oviedo, Spain. [Arranz, J. A.] Hosp Gen Univ Gregorio Maranon, Dept Med Oncol, Madrid, Spain. [Climent, M. A.] Fundac Inst Valenciano Oncol, Dept Med Oncol, Valencia, Spain. [Castellano, D. E.] Hosp Univ 12 Octubre, Dept Med Oncol, Madrid, Spain. [Bellmunt, J.] Univ Hosp Mar IMIM, Dept Med Oncol, Barcelona, Spain. [Bellmunt, J.] Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA USA. [Mellado, B.] Hosp Clin Univ Barcelona, Dept Med Oncol, Barcelona, Spain. [Puente, J.] Hosp Clin Univ San Carlos, Dept Med Oncol, Madrid, Spain. [Font, A.] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Dept Med Oncol, Barcelona, Spain. [Hernando, S.] Hosp Univ Fdn Alcorcon, Dept Med Oncol, Madrid, Spain. [Rodriguez-Antona, C.] CIBERER, Madrid, Spain. RP Rodriguez-Antona, C (reprint author), Spanish Natl Canc Res Ctr CNIO, Hereditary Endocrine Canc Grp, Human Canc Genet Programme, Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM crodriguez@cnio.es RI Rodriguez-Antona, Cristina/E-1073-2011; Robledo, Mercedes/O-2230-2013; OI Rodriguez-Antona, Cristina/0000-0001-8750-7338; Robledo, Mercedes/0000-0001-6256-5902; Garcia-Donas, Jesus/0000-0001-7731-3601; Morente, Manuel M/0000-0001-6004-330X FU Pfizer [SUT-REN-07] FX This study was supported by an unrestricted educational grant from Pfizer (SUT-REN-07) that played no role in study design, collection, analysis or interpretation of data, writing the report or the decision to submit the paper for publication. NR 24 TC 27 Z9 28 U1 4 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2013 VL 24 IS 9 BP 2409 EP 2414 DI 10.1093/annonc/mdt219 PG 6 WC Oncology SC Oncology GA 212DT UT WOS:000323963100032 PM 23788753 ER PT J AU Mathisen, DJ AF Mathisen, Douglas J. TI Is Video-Assisted Thoracoscopic Lobectomy Inferior to Open Lobectomy Oncologically? SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID LYMPH-NODE EVALUATION C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 6 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2013 VL 96 IS 3 BP 755 EP 756 DI 10.1016/j.athoracsur.2013.05.011 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 211VT UT WOS:000323940200011 PM 23992686 ER PT J AU Jacobs, JP He, X O'Brien, SM Welke, KF Filardo, G Han, JM Ferraris, VA Prager, RL Shahian, DM AF Jacobs, Jeffrey P. He, Xia O'Brien, Sean M. Welke, Karl F. Filardo, Giovanni Han, Jane M. Ferraris, Victor A. Prager, Richard L. Shahian, David M. TI Variation in Ventilation Time After Coronary Artery Bypass Grafting: An Analysis From The Society of Thoracic Surgeons Adult Cardiac Surgery Database SO ANNALS OF THORACIC SURGERY LA English DT Article ID INTENSIVE-CARE-UNIT; MECHANICAL VENTILATION; QUALITY MEASUREMENT; CONSEQUENCES; EXTUBATION; RATIONALE; OUTCOMES; PATIENT AB Background. Short postoperative ventilation times are accepted as a marker of quality. This analysis assesses center level variation in postoperative ventilation time in a subset of patients undergoing isolated coronary artery bypass grafting (CABG). Methods. In 2009 and 2010, 325,129 patients in the STS Adult Cardiac Surgery Database underwent isolated CABG. Patients were excluded if they were intubated before entering the operating room, required ventilation for greater than 24 hours, or had missing data on key covariates. The final study cohort was 274,231 isolated CABG patients from 1,008 centers. Bayesian hierarchical models were used to assess between-center variation in ventilation time and to explore the effect of center-level covariates. Analyses were performed with and without adjusting for case mix. Results. After adjusting for case mix, the ratio of median ventilator time at the 90th percentile of the center-level distribution compared with the tenth percentile was 9.0:5.0 = 1.8 (95% credible interval: 1.79 to 1.85). This ratio illustrates the scale of between-center differences: centers above the 90th percentile have a ventilation time of at least 1.8 times that of centers below the tenth percentile. Smaller hospital volume, presence of a residency program, and some census regions were associated with longer ventilation times. Conclusions. After adjustment for severity of illness, substantial inter-center variation exists in postoperative ventilation time in this subset of patients undergoing isolated CABG. This finding represents an opportunity for multi-institutional quality improvement initiatives designed to limit variations in ventilator management and achieve the shortest possible ventilation times for all patients, thus benefiting both clinical outcomes and resource utilization. (C) 2013 by The Society of Thoracic Surgeons C1 Johns Hopkins Childrens Heart Surg, All Childrens Hosp, St Petersburg, FL 33701 USA. Johns Hopkins Childrens Heart Surg, All Childrens Hosp, Tampa, FL USA. Johns Hopkins Childrens Heart Surg, All Childrens Hosp, Orlando, FL USA. Florida Hosp Children, St Petersburg, FL USA. Florida Hosp Children, Tampa, FL USA. Florida Hosp Children, Orlando, FL USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Seattle Childrens Hosp, Seattle, WA USA. Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. Soc Thorac Surg, Chicago, IL USA. Univ Kentucky, Lexington, KY USA. Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Qual & Safety, Boston, MA USA. RP Jacobs, JP (reprint author), Johns Hopkins Childrens Heart Surg, 601 5th St S,Ste 607, St Petersburg, FL 33701 USA. EM jjacobs@msn.com NR 22 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2013 VL 96 IS 3 BP 757 EP 762 DI 10.1016/j.athoracsur.2013.03.059 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 211VT UT WOS:000323940200012 PM 23731610 ER PT J AU Wagner, TH Hattler, B Bishawi, M Baltz, JH Collins, JF Quin, JA Grover, FL Shroyer, ALW AF Wagner, Todd H. Hattler, Brack Bishawi, Muath Baltz, Janet H. Collins, Joseph F. Quin, Jacquelyn A. Grover, Frederick L. Shroyer, A. Laurie W. CA VA 517 Randomized On Off Bypass TI On-Pump versus Off-Pump Coronary Artery Bypass Surgery: Cost-Effectiveness Analysis Alongside a Multisite Trial SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Late-Breaking Clinical Trial Abstract Session at the 49th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-30, 2013 CL Los Angeles, CA SP Soc Thorac Surg ID GRAFT PATENCY; ROOBY TRIAL; OUTCOMES AB Background. Questions have been raised about the costs and outcomes for patients receiving on-pump and off-pump coronary artery bypass graft surgery. As part of the Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) multisite trial, a cost-effectiveness analysis was performed to compare on-pump versus off-pump patients' quality-adjusted life-years and costs at 1 year. Methods. One-year outcomes and costs (standardized to 2010 dollars) were estimated in multivariate regression models, controlling for site and baseline patient factors. The 1-year incremental cost-effectiveness analysis ratio with 95% confidence intervals was calculated using bootstrapping. Results. Eighteen centers randomly assigned 2,203 participants to on-pump (n = 1,099) versus off-pump (n = 1,104) coronary artery bypass graft surgery. Both groups' quality of life improved significantly after surgery (p < 0.01) compared with baseline, but no differences were found between treatment groups. Adjusted cost of the index coronary artery bypass graft surgery hospitalization was $36,046 on-pump and $36,536 off-pump (p = 0.16). At 1 year, on-pump adjusted cost was $56,023 versus $59,623 off-pump (p = 0.046). Off-pump-to-on-pump conversions after first distal anastomosis (4.8%) had significantly higher 1-year costs. Excluding conversions, there were no significant differences between treatments for index hospitalization or 1-year total costs. Conclusions. At 1 year, off-pump coronary artery bypass graft surgery was more expensive than on-pump when late off-pump-to-on-pump conversions were included. Excluding late conversions, there was no difference in quality-adjusted life-years or costs. Trial Registration: ClinicalTrials.gov identifier NCT00032630; http://clinicaltrials.gov/ct2/show/NCT00032630. (C) 2013 by The Society of Thoracic Surgeons C1 VA Palo Alto Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA. Univ Colorado, Sch Med, Aurora, CO USA. Northport VA Med Ctr, Northport, NY USA. Cooperat Studies Program Coordinating Ctr, Vet Affairs Med Ctr, Perry Point, MD USA. VA Boston Healthcare Syst, West Roxbury, MA USA. RP Wagner, TH (reprint author), Stanford Univ, VA Palo Alto Hlth Econ Resource Ctr HERC, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA. EM todd.wagner@va.gov RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 22 TC 10 Z9 10 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2013 VL 96 IS 3 BP 770 EP 777 DI 10.1016/j.athoracsur.2013.04.074 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 211VT UT WOS:000323940200014 PM 23916805 ER PT J AU Izar, B Sequist, L Lee, M Muzikansky, A Heist, R Iafrate, J Dias-Santagata, D Mathisen, D Lanuti, M AF Izar, Benjamin Sequist, Lecia Lee, Mihan Muzikansky, Alona Heist, Rebecca Iafrate, John Dias-Santagata, Dora Mathisen, Douglas Lanuti, Michael TI The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers SO ANNALS OF THORACIC SURGERY LA English DT Article ID GROWTH-FACTOR RECEPTOR; GENE-MUTATIONS; GEFITINIB; KRAS; ADENOCARCINOMA; CHEMOTHERAPY; ERLOTINIB; CARBOPLATIN; PACLITAXEL; TUMORS AB Background. Mutations of the epidermal growth factor hormone receptor (EGFR) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy. Methods. Mutation status was tested in treatment-naive patients who had complete resection of stage I (T1-2aN0) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction-based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR-mutant and wild-type patients using Kaplan-Meier methods and Cox regression models. Results. Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p = 0.03), greater median disease-free survival (8.8 versus 7.0 years; p = 0.0085), and improved overall 5-year survival (98% versus 73%; p = 0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p = 0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation (p = 0.026) and tumor size less than 2 cm (p = 0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not. Conclusions. Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC. (C) 2013 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Div Thorac Surg,Biostat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lanuti, M (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@partners.org FU Division of Thoracic Surgery at the Massachusetts General Hospital FX Financial support for this study was provided by the Division of Thoracic Surgery at the Massachusetts General Hospital. We would like to acknowledge our data manager and research coordinator, Sheila Cann and Diane Davies, respectively, for their diligence and dedication toward compiling and maintaining the Thoracic Surgery Database. NR 21 TC 26 Z9 28 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2013 VL 96 IS 3 BP 962 EP 968 DI 10.1016/j.athoracsur.2013.05.091 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 211VT UT WOS:000323940200041 PM 23932319 ER PT J AU Fitzsimons, MG Ng, J Wright, C Mathisen, D Vlahakes, G Albrecht, M AF Fitzsimons, Michael G. Ng, Joshua Wright, Cameron Mathisen, Douglas Vlahakes, Gus Albrecht, Meredith TI Carinal Resection Requiring Cardiopulmonary Bypass in a Pregnant Patient SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material AB A 35-year-old woman at 13 weeks gestation presented with adenoid cystic carcinoma of the distal left mainstem bronchus with chronic collapse of the left lung requiring carinal pneumonectomy. The extent of the tumor and need for significant retraction during dissection and pneumonectomy resulted in the need for cardiopulmonary bypass. The patient underwent successful left carinal pneumonectomy and subsequently delivered a healthy baby. (C) 2013 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Thorac Surg Div, Dept Surg, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Dept Surg, Boston, MA 02114 USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Div Cardiac Anesthesia, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2013 VL 96 IS 3 BP 1085 EP 1087 DI 10.1016/j.athoracsur.2012.12.048 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 211VT UT WOS:000323940200066 PM 23992710 ER PT J AU Cai, C Zhong, WD McDougal, WS Wu, CL AF Cai, Chao Zhong, Wei-De McDougal, W. Scott Wu, Chin-Lee TI A 32-gene risk index: a new prognostic approach for prostate cancer progression SO ASIAN JOURNAL OF ANDROLOGY LA English DT Editorial Material ID RADICAL PROSTATECTOMY AB Radical prostatectomy (RP) has been a widely accepted and standard treatment for clinically localized and locally advanced prostate cancer. However, effective clinical management of RP patient remains being challenged, given that conventional prognostic factors, including Gleason score, pT stage, surgical margin status and presurgery serum prostate-specific antigen (PSA), cannot correctly predict cancer recurrence after RP. Recently, a robust prognostic model for biochemical recurrence (BCR) and metastasis has been developed by our group at the MGH. This model was a continuous risk index based on the expression of 32 genes and was validated in an independent, blinded cohort of 270 RP patients. In multivariate analyses, the 32-gene risk index model was prognostic for risk of BCR and had added value over the traditional parameters. This model may contribute to accurate postoperative treatment decision and hopefully help patients and doctors make a more reasonable selection at the stage of a positive biopsy. C1 [Cai, Chao; McDougal, W. Scott; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Cai, Chao; McDougal, W. Scott; Wu, Chin-Lee] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Cai, Chao] Southern Med Univ, Grad Sch, Guangzhou 510515, Guangdong, Peoples R China. [Zhong, Wei-De] Guangzhou First Municipal Peoples Hosp, Dept Urol, Guangzhou 510180, Guangdong, Peoples R China. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wu, CL (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM cwu2@partners.org OI Zhong, Weide/0000-0002-0430-2845 NR 8 TC 0 Z9 0 U1 1 U2 2 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1008-682X J9 ASIAN J ANDROL JI Asian J. Androl. PD SEP PY 2013 VL 15 IS 5 BP 590 EP 591 DI 10.1038/aja.2013.85 PG 2 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 211TF UT WOS:000323933000006 PM 23749003 ER PT J AU Johnson, KA Sperling, RA Sepulcre, J AF Johnson, Keith A. Sperling, Reisa A. Sepulcre, Jorge TI Functional Connectivity in Alzheimer's Disease: Measurement and Meaning SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 [Johnson, Keith A.; Sepulcre, Jorge] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Johnson, Keith A.; Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Johnson, Keith A.; Sepulcre, Jorge] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.; Sepulcre, Jorge] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Keith A.; Sepulcre, Jorge] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Sperling, Reisa A.; Sepulcre, Jorge] Athinioula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Johnson, KA (reprint author), Massachusetts Gen Hosp, White 427,33 Fruit St, Boston, MA 02114 USA. EM kajohnson@pet.mgh.harvard.edu NR 5 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2013 VL 74 IS 5 BP 318 EP 319 DI 10.1016/j.biopsych.2013.07.010 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 213IT UT WOS:000324050500002 PM 23932342 ER PT J AU Kornblit, B Maloney, DG Storb, R Storek, J Hari, P Vucinic, V Maziarz, RT Chauncey, TR Pulsipher, MA Bruno, B Petersen, FB Bethge, WA Hubel, K Bouvier, ME Fukuda, T Storer, BE Sandmaier, BM AF Kornblit, Brian Maloney, David G. Storb, Rainer Storek, Jan Hari, Parameswaran Vucinic, Vladan Maziarz, Richard T. Chauncey, Thomas R. Pulsipher, Michael A. Bruno, Benedetto Petersen, Finn B. Bethge, Wolfgang A. Huebel, Kai Bouvier, Michelle E. Fukuda, Takahiro Storer, Barry E. Sandmaier, Brenda M. TI Fludarabine and 2-Gy TBI is Superior to 2 Gy TBI as Conditioning for HLA-Matched Related Hematopoietic Cell Transplantation: A Phase III Randomized Trial SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Nonmyeloablative conditioning; Fludarabine/low dose total body irradiation; HLA-matched related hematopoietic cell transplantation randomized trial ID TOTAL-BODY IRRADIATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; HEMATOLOGIC MALIGNANCIES; MARROW TRANSPLANTATION; FOLLICULAR LYMPHOMA; RISK-ASSESSMENT; KILLER-CELLS; CHIMERISM; DONOR; INTENSITY AB The risks and benefits of adding fludarabine to a 2-Gy total body irradiation (TBI) nonmyeloablative regimen are unknown. For this reason, we conducted a prospective randomized trial comparing 2-Gy TBI alone, or in combination with 90 mg/m(2) fludarabine (FLU/TBI), before transplantation of peripheral blood stem cells from HLA-matched related donors. Eighty-five patients with hematological malignancies were randomized to be conditioned with TBI alone (n = 44) or FLU/TBI (n = 41). All patients had initial engraftment. Two graft rejections were observed, both in the TBI group. Infection rates, nonrelapse mortality, and graft-versus-host disease (GVHD) were similar between groups. Three-year overall survival was lower in the TBI group (54% versus 65%; hazard ratio [HR], .57; P = .09), with higher incidences of relapse/progression (55% versus 40%; HR, .55; P = .06), relapse-related mortality (37% versus 28%; HR, .53; P = .09), and a lower progression-free survival (36% versus 53%; HR, .56; P = .05). Median donor T cell chimerism levels were significantly lower in the TBI group at days 28 (61% versus 90%; P < .0001) and 84 (68% versus 92%; P < .0001), as was NK cell chimerism on day 28 (75% versus 96%; P = .0005). In conclusion, this randomized trial demonstrates the importance of fludarabine in augmenting the graft-versus-tumor effect by ensuring prompt and durable high-level donor engraftment early after transplantation. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Kornblit, Brian; Maloney, David G.; Storb, Rainer; Chauncey, Thomas R.; Bouvier, Michelle E.; Storer, Barry E.; Sandmaier, Brenda M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Maloney, David G.; Storb, Rainer; Sandmaier, Brenda M.] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA. [Storek, Jan] Univ Calgary, Dept Med, Calgary, AB, Canada. [Storek, Jan] Univ Calgary, Dept Oncol & Microbiol, Calgary, AB, Canada. [Storek, Jan] Univ Calgary, Dept Immunol, Calgary, AB, Canada. [Storek, Jan] Univ Calgary, Dept Infect Dis, Calgary, AB, Canada. [Hari, Parameswaran] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Vucinic, Vladan] Univ Leipzig, Dept Hematol & Oncol, D-04109 Leipzig, Germany. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Marrow Transplant Unit, Seattle, WA USA. [Pulsipher, Michael A.] Univ Utah, Sch Med, Huntsman Canc Inst, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA. [Bruno, Benedetto] Univ Turin, Sch Med, Div Hematol, Turin, Italy. [Petersen, Finn B.] LDS Hosp, Intermt Blood & Marrow Transplant Acutr Leukemia, Salt Lake City, UT USA. [Bethge, Wolfgang A.] Univ Tubingen, Med Ctr, Dept Med, Tubingen, Germany. [Huebel, Kai] Univ Cologne, Ctr Integrated Oncol Cologne Bonn, Dept Med 1, D-50931 Cologne, Germany. [Fukuda, Takahiro] Natl Canc Ctr, Stem Cell Transplantat Div, Tokyo, Japan. [Storer, Barry E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM bsandmai@fhcrc.org OI Hari, Parameswaran/0000-0002-8800-297X FU National Institutes of Health, Bethesda, MD [CA078902, HL036444, CA015704]; Danish Cancer Society [DP08135]; Froken Amalie Jorgensens Mindelegat; Anders Hasselbalchs Fond; Ricerca Sanitaria Finalizzata [RF-PIE-2008-1206999, RF-PIE-2009-1491359] FX Financial disclosure: Research funding was provided by the National Institutes of Health, Bethesda, MD, grants, CA078902, HL036444, and CA015704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health nor its subsidiary Institutes and Centers. B.K. was supported by a fellowship from the Danish Cancer Society (DP08135), Froken Amalie Jorgensens Mindelegat and Anders Hasselbalchs Fond. B.B. was supported by Ricerca Sanitaria Finalizzata RF-PIE-2008-1206999 and RF-PIE-2009-1491359. NR 36 TC 10 Z9 10 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2013 VL 19 IS 9 BP 1340 EP 1347 DI 10.1016/j.bbmt.2013.06.002 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 212WT UT WOS:000324014200009 PM 23769990 ER PT J AU Brunner, AM Kim, HT Coughlin, E Alyea, EP Armand, P Ballen, KK Cutler, C Dey, BR Glotzbecker, B Koreth, J McAfee, SL Spitzer, TR Soiffer, RJ Antin, JH Ho, VT Chen, YB AF Brunner, Andrew M. Kim, Haesook T. Coughlin, Erin Alyea, Edwin P., III Armand, Philippe Ballen, Karen K. Cutler, Corey Dey, Bimalangshu R. Glotzbecker, Brett Koreth, John McAfee, Steven L. Spitzer, Thomas R. Soiffer, Robert J. Antin, Joseph H. Ho, Vincent T. Chen, Yi-Bin TI Outcomes in Patients Age 70 or Older Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic transplantation; Aged; Mortality; Relapse; Graft versus host disease ID ACUTE MYELOID-LEUKEMIA; RISK MYELODYSPLASTIC SYNDROME; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; VERSUS-HOST-DISEASE; UNRELATED DONORS; ELDERLY-PATIENTS; COMPETING RISK; INTENSITY; REMISSION AB Allogeneic hematopoietic stem cell transplantation (HSCT) can achieve durable remissions in a number of patients with advanced hematologic malignancies. Little is known about the safety of HSCT in patients age 70 or older. Consecutive patients (n = 54) age 70 or older underwent HSCT between 2007 and 2012. Diseases included acute myelogenous leukemia (n = 25), myelodysplastic syndrome (n = 12), chronic lymphocytic leukemia (n = 5), non-Hodgkin lymphoma (n = 4), acute lymphoblastic leukemia (n = 3), myeloproliferative neoplasm (n = 4), and chronic myelogenous leukemia (n = 1). Median follow-up for survivors was 21 months. All patients received reduced-intensity conditioning regimens, primarily busulfan/fludarabine. All patients received unmanipulated peripheral blood stem cell grafts: 44 from 8/8 matched unrelated donors, 8 from matched related donors, and 2 from 7/8 matched unrelated donors. Graft-versus-host disease (GVHD) prophylaxis was calcineurin inhibitor based in all patients. The median age at transplantation was 71 years (range, 70 to 76); the median HCT comorbidity index score was 1 (range, 0 to 5). Two patients died before hematopoietic recovery (1 with graft failure and 1 with disease progression), and 1 patient relapsed before hematopoietic recovery; otherwise, all engrafted with median donor chimerism of 94% at 1 month. Cumulative incidence of grades II to IV acute GVHD was 13% and of grades III to IV acute GVHD, 9.3%. At 2 years, the cumulative incidence of chronic GVHD was 36%, progression-free survival was 39%, overall survival was 39%, and relapse was 56%. Nonrelapse mortality was 3.7% at day +100 and 5.6% at 2 years. We conclude that allogeneic HSCT is a safe and effective option for carefully selected patients age 70 or older. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Brunner, Andrew M.; Coughlin, Erin; Ballen, Karen K.; Dey, Bimalangshu R.; McAfee, Steven L.; Spitzer, Thomas R.; Chen, Yi-Bin] Massachusetts Gen Hosp, Div Hematol Oncol, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Alyea, Edwin P., III; Armand, Philippe; Cutler, Corey; Glotzbecker, Brett; Koreth, John; Soiffer, Robert J.; Antin, Joseph H.; Ho, Vincent T.] Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 106, Boston, MA 02114 USA. EM ychen6@partners.org NR 34 TC 26 Z9 28 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2013 VL 19 IS 9 BP 1374 EP 1380 DI 10.1016/j.bbmt.2013.06.008 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 212WT UT WOS:000324014200014 PM 23791626 ER PT J AU Cassaday, RD Guthrie, KA Budde, EL Thompson, L Till, BG Press, OW Chauncey, TR Pagel, JM Petersdorf, SH Palanca-Wessels, MC Philip, M Bensinger, WI Holmberg, LA Shustov, A Green, DJ Libby, EN Maloney, DG Gopal, AK AF Cassaday, Ryan D. Guthrie, Katherine A. Budde, Elizabeth L. Thompson, Leslie Till, Brian G. Press, Oliver W. Chauncey, Thomas R. Pagel, John M. Petersdorf, Stephen H. Palanca-Wessels, Maria Corinna Philip, Mary Bensinger, William I. Holmberg, Leona A. Shustov, Andrei Green, Damian J. Libby, Edward N. Maloney, David G. Gopal, Ajay K. TI Specific Features Identify Patients with Relapsed or Refractory Mantle Cell Lymphoma Benefitting from Autologous Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Mantle cell lymphoma; Autologous transplantation ID PROGRESSION-FREE SURVIVAL; PLUS RITUXIMAB; REMISSION; MULTICENTER; PHASE-2; REGIMEN; TRIAL; CHOP AB Outcomes with autologous hematopoietic cell transplantation (auto HCT) for relapsed and/or refractory mantle cell lymphoma (MCL) are typically poor. We hypothesized that certain factors could predict which patients experience a favorable outcome with this approach. We thus developed a predictive score from a cohort of 67 such patients using 3 factors independently associated with progression-free survival (PFS): (1) simplified Mantle Cell Lymphoma International Prognostic Index score before auto HCT (hazard ratio MR], 2.9; P = .002); (2) B symptoms at diagnosis (HR, 2.7; P = .005); and (3) remission quotient, calculated by dividing the time, in months, from diagnosis to auto HCT by the number of prior treatments (HR, 1.4; P = .02). The estimated 5-year PFS for favorable-risk patients (n = 23) and unfavorable-risk patients (n = 44) were 58% (95% confidence interval [CI], 34% to 75%) and 15% (95% Cl, 6% to 28%), respectively. These factors also independently predicted overall survival. In summary, we have defined 3 simple factors that can identify patients with relapsed/refractory MCL who derive a durable benefit from salvage auto HCT. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Cassaday, Ryan D.; Guthrie, Katherine A.; Budde, Elizabeth L.; Thompson, Leslie; Till, Brian G.; Press, Oliver W.; Chauncey, Thomas R.; Pagel, John M.; Petersdorf, Stephen H.; Palanca-Wessels, Maria Corinna; Philip, Mary; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei; Green, Damian J.; Libby, Edward N.; Maloney, David G.; Gopal, Ajay K.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Cassaday, Ryan D.; Budde, Elizabeth L.; Thompson, Leslie; Till, Brian G.; Press, Oliver W.; Chauncey, Thomas R.; Pagel, John M.; Petersdorf, Stephen H.; Bensinger, William I.; Holmberg, Leona A.; Green, Damian J.; Libby, Edward N.; Maloney, David G.; Gopal, Ajay K.] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA USA. [Chauncey, Thomas R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Palanca-Wessels, Maria Corinna; Philip, Mary; Shustov, Andrei] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA. RP Gopal, AK (reprint author), 825 Eastlake Ave E,Mailstop G3-200, Seattle, WA 98109 USA. EM agopal@u.washington.edu FU Lymphoma Research Foundation MCL Initiative; Leukemia and Lymphoma Society; NIH [T32 CA009515-27, P01 CA044991]; NCI [K08 CA163603, K08 CA151682]; Mary Wright Memorial Fund FX This work was supported by The Lymphoma Research Foundation MCL Initiative, a Clinical Scholar Award by the Leukemia and Lymphoma Society (A.K.G.), NIH T32 CA009515-27 (R.D.C.), NCI K08 CA163603 (M.C.P.W.), NCI K08 CA151682 (N.G.), NIH P01 CA044991, the Mary Wright Memorial Fund, and gifts from David and Patricia Giuliani, Frank and Betty Vandermeer, and Don and Debbie Hunkins. NR 19 TC 8 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2013 VL 19 IS 9 BP 1403 EP 1406 DI 10.1016/j.bbmt.2013.07.005 PG 4 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 212WT UT WOS:000324014200020 PM 23871782 ER PT J AU Gambra, E Ortiz, S Perez-Merino, P Gora, M Wojtkowski, M Marcos, S AF Gambra, Enrique Ortiz, Sergio Perez-Merino, Pablo Gora, Michalina Wojtkowski, Maciej Marcos, Susana TI Static and dynamic crystalline lens accommodation evaluated using quantitative 3-D OCT SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; SWEPT SOURCE OCT; EQUIVALENT REFRACTIVE-INDEX; ANTERIOR SEGMENT BIOMETRY; HUMAN EYE; CORNEAL TOPOGRAPHY; SHAPE; SCHEIMPFLUG; ABERRATIONS; SYSTEM AB Custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT) provided with automatic quantification and distortion correction algorithms was used to characterize three-dimensionally (3-D) the human crystalline lens in vivo in four subjects, for accommodative demands between 0 to 6 D in 1 D steps. Anterior and posterior lens radii of curvature decreased with accommodative demand at rates of 0.73 and 0.20 mm/D, resulting in an increase of the estimated optical power of the eye of 0.62 D per diopter of accommodative demand. Dynamic fluctuations in crystalline lens radii of curvature, anterior chamber depth and lens thickness were also estimated from dynamic 2-D OCT images (14 Hz), acquired during 5-s of steady fixation, for different accommodative demands. Estimates of the eye power from dynamical geometrical measurements revealed an increase of the fluctuations of the accommodative response from 0.07 D to 0.47 D between 0 and 6 D (0.044 D per D of accommodative demand). A sensitivity analysis showed that the fluctuations of accommodation were driven by dynamic changes in the lens surfaces, particularly in the posterior lens surface. (C) 2013 Optical Society of America C1 [Gambra, Enrique; Ortiz, Sergio; Perez-Merino, Pablo; Marcos, Susana] CSIC, Inst Opt Daza de Valdes, Madrid 28006, Spain. [Gora, Michalina; Wojtkowski, Maciej] Nicholas Copernicus Univ, Fac Phys Astron & Informat, Inst Phys, PL-87100 Torun, Poland. [Gora, Michalina] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Gora, Michalina] Harvard Univ, Sch Med, Boston, MA USA. RP Gambra, E (reprint author), CSIC, Inst Opt Daza de Valdes, C Serrano 121, Madrid 28006, Spain. EM e.gambra@io.cfmac.csic.es RI Wojtkowski, Maciej/D-6822-2014 FU EU [EURYI-01/2008-PL]; MICINN [FIS2011-02065]; European Research Council under European Union [294099]; [CSIC-I3P2006] FX The authors acknowledge funding from Predoctoral fellowship CSIC-I3P2006 to EG; FNP Ventures Program co-financed by the EU Funds to MG; EURYI-01/2008-PL (EURHORCs) to MW; MICINN FIS2011-02065 to SM. The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013) / ERC Grant Agreement n. [294099] to SM. The authors acknowledge technical hardware and software support of Ireneusz Grulkowski and Maciej Szkulmowski from NCU Torun. The authors thank the subjects for their contribution to this study. NR 50 TC 11 Z9 11 U1 1 U2 13 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD SEP 1 PY 2013 VL 4 IS 9 BP 1595 EP 1609 DI 10.1364/BOE.4.001595 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 211FD UT WOS:000323889800010 PM 24049680 ER PT J AU Schlachter, SC Kang, DK Gora, MJ Vacas-Jacques, P Wu, T Carruth, RW Wilsterman, EJ Bouma, BE Woods, K Tearney, GJ AF Schlachter, Simon C. Kang, DongKyun Gora, Michalina J. Vacas-Jacques, Paulino Wu, Tao Carruth, Robert W. Wilsterman, Eric J. Bouma, Brett E. Woods, Kevin Tearney, Guillermo J. TI Spectrally encoded confocal microscopy of esophageal tissues at 100 kHz line rate SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID IN-VIVO; LASER ENDOMICROSCOPY; DIAGNOSIS AB Spectrally encoded confocal microscopy (SECM) is a reflectance confocal microscopy technology that uses a diffraction grating to illuminate different locations on the sample with distinct wavelengths. SECM can obtain line images without any beam scanning devices, which opens up the possibility of high-speed imaging with relatively simple probe optics. This feature makes SECM a promising technology for rapid endoscopic imaging of internal organs, such as the esophagus, at microscopic resolution. SECM imaging of the esophagus has been previously demonstrated at relatively low line rates (5 kHz). In this paper, we demonstrate SECM imaging of large regions of esophageal tissues at a high line imaging rate of 100 kHz. The SECM system comprises a wavelength-swept source with a fast sweep rate (100 kHz), high output power (80 mW), and a detector unit with a large bandwidth (100 MHz). The sensitivity of the 100-kHz SECM system was measured to be 60 dB and the transverse resolution was 1.6 mu m. Excised swine and human esophageal tissues were imaged with the 100-kHz SECM system at a rate of 6.6 mm(2)/sec. Architectural and cellular features of esophageal tissues could be clearly visualized in the SECM images, including papillae, glands, and nuclei. These results demonstrate that large-area SECM imaging of esophageal tissues can be successfully conducted at a high line imaging rate of 100 kHz, which will enable whole-organ SECM imaging in vivo. (C) 2013 Optical Society of America C1 [Schlachter, Simon C.; Kang, DongKyun; Gora, Michalina J.; Vacas-Jacques, Paulino; Wu, Tao; Carruth, Robert W.; Wilsterman, Eric J.; Bouma, Brett E.; Woods, Kevin; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Schlachter, Simon C.; Kang, DongKyun; Gora, Michalina J.; Vacas-Jacques, Paulino; Wu, Tao; Carruth, Robert W.; Wilsterman, Eric J.; Bouma, Brett E.; Woods, Kevin; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Bouma, Brett E.; Tearney, Guillermo J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schlachter, SC (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM gtearney@partners.org FU Nine Point Medical, Cambridge, MA; Nine Point Medical FX This research was supported by a sponsored research agreement with Nine Point Medical, Cambridge, MA. Dr. Schlachter is currently with Nine Point Medical. Dr. Woods is currently with Emory University Hospital, Atlanta, GA. Drs. Tearney and Bouma receive sponsored research from and consult for Nine Point Medical. Nine Point Medical has a licensing arrangement with Massachusetts General Hospital. Drs. Schlachter, Kang, Gora, Carruth, Bouma and Tearney have the right to receive royalties from this licensing arrangement. NR 18 TC 9 Z9 11 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD SEP 1 PY 2013 VL 4 IS 9 BP 1636 EP 1645 DI 10.1364/BOE.4.001636 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 211FD UT WOS:000323889800014 PM 24049684 ER PT J AU Lewis, LD Ching, SN Weiner, VS Peterfreund, RA Eskandar, EN Cash, SS Brown, EN Purdon, PL AF Lewis, Laura D. Ching, ShiNung Weiner, Veronica S. Peterfreund, Robert A. Eskandar, Emad N. Cash, Sydney S. Brown, Emery N. Purdon, Patrick L. TI Local cortical dynamics of burst suppression in the anaesthetized brain SO BRAIN LA English DT Article DE intracranial electroencephalogram; human; neurophysiology; general anaesthesia ID REFRACTORY STATUS EPILEPTICUS; GENERAL-ANESTHESIA; PROPOFOL; ELECTROENCEPHALOGRAM; SLEEP; EEG; CONSCIOUSNESS; ISOFLURANE; COMA AB Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric 'suppressions' lasting seconds or minutes, and high-voltage 'bursts'. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a 'global' state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly, subcortical circuits express seemingly different sensitivities to high doses of anaesthetics that suggest a hierarchy governing how the brain enters burst suppression, and emphasize the role of local dynamics in what has previously been regarded as a global state. These findings suggest a conceptual shift in how neurologists could assess the brain function of patients undergoing burst suppression. First, analysing spatial variation in burst suppression could provide insight into the circuit dysfunction underlying a given pathology, and could improve monitoring of medically-induced coma. Second, analysing the temporal dynamics within a burst could help assess the underlying brain state. This approach could be explored as a prognostic tool for recovery from coma, and for guiding treatment of status epilepticus. Overall, these results suggest new research directions and methods that could improve patient monitoring in clinical practice. C1 [Lewis, Laura D.; Ching, ShiNung; Weiner, Veronica S.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Ching, ShiNung] Washington Univ, Dept Elect & Syst Engn, St Louis, MO 63130 USA. [Peterfreund, Robert A.; Brown, Emery N.; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Peterfreund, Robert A.; Brown, Emery N.; Purdon, Patrick L.] Harvard Univ, Dept Anaesthesia, Sch Med, Boston, MA 02115 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Eskandar, Emad N.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cash, Sydney S.] Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Brown, Emery N.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Purdon, PL (reprint author), CNY 149-4,149 13th St, Charlestown, MA 02129 USA. EM patrickp@nmr.mgh.harvard.edu FU Canadian Institutes of Health Research; Burroughs-Wellcome Fund; National Institutes of Health [DP1OD003646]; National Institutes of Health (NIH) [1R01GM104948, DP2-OD006454] FX This work was supported by a doctoral fellowship from the Canadian Institutes of Health Research to L. D. L., a Career Award at the Scientific Interface from the Burroughs-Wellcome Fund to S. C., and by the National Institutes of Health [Director's Pioneer Award DP1OD003646 to E.N.B., NIH Transformative 1R01GM104948 to E.N.B., NIH New Innovator Award DP2-OD006454 to P.L.P.]. NR 26 TC 26 Z9 26 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2013 VL 136 BP 2727 EP 2737 DI 10.1093/brain/awt174 PN 9 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 212EM UT WOS:000323965100013 PM 23887187 ER PT J AU Pasinetti, GM Bilski, AE Zhao, W AF Pasinetti, Giulio Maria Bilski, Amanda E. Zhao, Wei TI Sirtuins as therapeutic targets of ALS SO CELL RESEARCH LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; SURVIVAL C1 [Pasinetti, Giulio Maria; Bilski, Amanda E.; Zhao, Wei] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria; Zhao, Wei] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Room 20-02, New York, NY 10029 USA. EM Giulio.Pasinetti@mssm.edu NR 10 TC 5 Z9 5 U1 1 U2 10 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD SEP PY 2013 VL 23 IS 9 BP 1073 EP 1074 DI 10.1038/cr.2013.94 PG 2 WC Cell Biology SC Cell Biology GA 211SH UT WOS:000323930200006 PM 23856645 ER PT J AU Ortega, F Counter, SA Buchanan, LH Parra, AMC Collaguaso, MA Jacobs, AB Rifai, N Hoover, PN AF Ortega, Fernando Counter, S. Allen Buchanan, Leo H. Coronel Parra, Angelica M. Angela Collaguaso, Maria Jacobs, Anthony B. Rifai, Nader Hoover, Patricia Nolan TI Declining blood lead and zinc protoporphyrin levels in Ecuadorian Andean children SO CLINICAL BIOCHEMISTRY LA English DT Article DE Children; Blood; Lead; Zinc protoporphyrin; Andes ID GLOBAL BURDEN; BREAST-MILK; EXPOSURE; INTOXICATION; IMPAIRMENT AB Objectives: To investigate current lead (Pb) exposure in children living in Andean Ecuadorian communities. Blood Pb (PbB) and zinc protoporphyrin (ZPP) levels were used respectively as biomarkers of acute and chronic Pb poisoning. The current PbB-ZPP levels were compared with previous pediatric PbB-ZPP levels recorded over years in the study area. Design and methods: Samples of whole blood were collected from 22 Andean children of Quechua and Mestizo backgrounds and measured for PbB concentrations by graphite furnace atomic absorption spectroscopy. ZPP/heme ratio and ZPP whole blood (ZPP WB) levels were measured with a hematofluorometer. Results: The mean PbB level for children in the current study group was 14.5 mu g/dL, which was significantly lower than the mean PbB level of 41.1 mu g/dL found in the same study area in the 1996-2000 test period, and lower than the 222 mu g/dL mean level found in the 2003-2007 period. The current mean ZPP/heme ratio was 102.1 mu mol/mol, and the mean ZPP WB level was 46.3 mu g/dL, both lower than values previously found in children in the study area. Conclusion: While the current pediatric PbB-ZPP levels in the study area remain elevated in some children, the overall levels indicate a decline relative to levels observed in the same Pb-contaminated area in the period between 1996 and 2007. The elevated ZPP levels suggest a history of chronic Pb exposure, and potential iron deficiency in some children. The overall reduction in PbB-ZPP levels suggests a positive outcome of a Pb-exposure education and prevention program, and the therapeutic intervention of succimer chelation therapy. (c) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Ortega, Fernando] Univ San Francisco Quito, Escuela Salud Publ, Colegio Artes Liberales, Colegio Ciencias Salud,Escuela Med, Quito, Ecuador. [Ortega, Fernando] Univ San Francisco Quito, Galapagos Inst Arts & Sci GAIAS, Quito, Ecuador. [Counter, S. Allen] Harvard Univ, Sch Med, Biol Labs, Dept Neurol, Cambridge, MA 02138 USA. [Counter, S. Allen] Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. [Buchanan, Leo H.] Univ Massachusetts, Eunice Kennedy Shriver Ctr, Sch Med, Dept Pediat, Waltham, MA USA. [Buchanan, Leo H.] Harvard Univ Hlth Serv, Dept Otolaryngol, Cambridge, MA USA. [Coronel Parra, Angelica M.; Angela Collaguaso, Maria] Subctr Salud, Pujili, Cotopaxi, Ecuador. [Jacobs, Anthony B.] Harvard Biol Labs, Cambridge, MA USA. [Rifai, Nader; Hoover, Patricia Nolan] Boston Childrens Hosp, Dept Lab Med, Boston, MA USA. [Rifai, Nader] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Biol Labs, Dept Neurol, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu FU Harvard Biological Laboratories; Harvard University Health Services; Eunice Kennedy Shriver Center/University of Massachusetts Medical School; NIH [P30 HD04147] FX The authors thank Universidad San Francisco de Quito College of Health Sciences and Medical School for continued support of this project. We thank Dr. Gonzalo Mantilla, Dean of the College of Health Sciences, Universidad San Francisco de Quito Medical School, for ongoing support and advice. We thank Gladys Pacheco, Nurse at the Subcentro de Salud, La Victoria, Ecuador for assistance. The Minister of Public Health of Ecuador, Carina Vance Mafla, is thanked for her consultation and Ministry of Public Health staff support. The authors are grateful to Dr. Merilee Grind le, Director of the David Rockefeller Center for Latin American Studies at Harvard, and Monica Tesoriero. We thank Dr. Jeremy Bloxham, Dean of Science, Harvard University; Harvard Biological Laboratories, Harvard University Health Services, and Eunice Kennedy Shriver Center/University of Massachusetts Medical School for support. LHB is supported in part by NIH grant P30 HD04147. NR 27 TC 3 Z9 3 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD SEP PY 2013 VL 46 IS 13-14 SI SI BP 1233 EP 1238 DI 10.1016/j.clinbiochem.2013.05.002 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 210TK UT WOS:000323857300012 PM 23684775 ER PT J AU Khalili, H Chan, AT AF Khalili, Hamed Chan, Andrew T. TI Bisphosphonate Use and Risk of Colorectal Cancer SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter ID IMPACT; WOMEN; LIFE C1 [Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Khalili, H (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2013 VL 11 IS 9 BP 1208 EP 1209 DI 10.1016/j.cgh.2013.04.040 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 210FU UT WOS:000323816100033 PM 23660421 ER PT J AU Pape, HC Vrahas, MS AF Pape, Hans-Christoph Vrahas, Mark S. TI Symposium: Tscherne Festschrift: Editorial Comment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Editorial Material C1 [Pape, Hans-Christoph] Univ Aachen, Med Ctr, Dept Orthopaed Trauma, Aachen, Germany. [Vrahas, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Pape, HC (reprint author), Univ Aachen, Med Ctr, Dept Orthopaed Trauma, Aachen, Germany. EM hpape@ukaachen.de NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2013 VL 471 IS 9 BP 2751 EP 2752 DI 10.1007/s11999-013-3173-6 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 197VK UT WOS:000322879800006 PM 23888324 ER PT J AU Ring, DC AF Ring, David C. TI CORR Insights((R)): The Peripheral Neuronal Phenotype is Important in the Pathogenesis of Painful Human Tendinopathy: A Systematic Review SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Editorial Material ID INJECTION; TRIAL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 6 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2013 VL 471 IS 9 BP 3047 EP 3048 DI 10.1007/s11999-013-3039-y PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 197VK UT WOS:000322879800045 PM 23661299 ER PT J AU Hinton, DE Peou, S Joshi, S Nickerson, A Simon, NM AF Hinton, Devon E. Peou, Sonith Joshi, Siddharth Nickerson, Angela Simon, Naomi M. TI Normal Grief and Complicated Bereavement Among Traumatized Cambodian Refugees: Cultural Context and the Central Role of Dreams of the Dead SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Grief; Complicated bereavement; Mass trauma; Cambodia; PTSD ID ATTACKS; WOMEN; PTSD AB This article profiles bereavement among traumatized Cambodian refugees and explores the validity of a model of how grief and post-traumatic stress disorder (PTSD) interact in this group to form a unique bereavement ontology, a model in which dreams of the dead play a crucial role. Several studies were conducted at a psychiatric clinic treating Cambodian refugees who survived the Pol Pot genocide. Key findings included that Pol Pot deaths were made even more deeply disturbing owing to cultural ideas about "bad death" and the consequences of not performing mortuary rites; that pained recall of the dead in the last month was common (76 % of patients) and usually caused great emotional and somatic distress; that severity of pained recall of the dead was strongly associated with PTSD severity (r = .62); that pained recall was very often triggered by dreaming about the dead, usually of someone who died in the Pol Pot period; and that Cambodians have a complex system of interpretation of dreams of the deceased that frequently causes those dreams to give rise to great distress. Cases are provided that further illustrate the centrality of dreams of the dead in the Cambodian experiencing of grief and PTSD. The article shows that not assessing dreams and concerns about the spiritual status of the deceased in the evaluation of bereavement results in "category truncation," i.e., a lack of content validity, a form of category fallacy. C1 [Hinton, Devon E.; Simon, Naomi M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hinton, Devon E.; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Hinton, Devon E.] Arbour Counseling Serv, Lowell, MA USA. [Peou, Sonith] Lowell Community Hlth Ctr, Lowell, MA USA. [Joshi, Siddharth] CBC Med Ctr, Southeast Asian Clin, Lowell, MA USA. [Nickerson, Angela] Univ New S Wales, Sch Psychol, Kensington, NSW 2033, Australia. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu FU NIMH NIH HHS [R01 MH094312] NR 26 TC 7 Z9 7 U1 7 U2 26 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD SEP PY 2013 VL 37 IS 3 BP 427 EP 464 DI 10.1007/s11013-013-9324-0 PG 38 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 209EE UT WOS:000323736300003 PM 23868080 ER PT J AU Nepple, KG Stephenson, AJ Kallogjeri, D Michalski, J Grubb, RL Strope, SA Haslag-Minoff, J Piccirillo, JF Ciezki, JP Klein, EA Reddy, CA Yu, CH Kattan, MW Kibel, AS AF Nepple, Kenneth G. Stephenson, Andrew J. Kallogjeri, Dorina Michalski, Jeff Grubb, Robert L., III Strope, Seth A. Haslag-Minoff, Jennifer Piccirillo, Jay F. Ciezki, Jay P. Klein, Eric A. Reddy, Chandana A. Yu, Changhong Kattan, Michael W. Kibel, Adam S. TI Mortality After Prostate Cancer Treatment with Radical Prostatectomy, External-Beam Radiation Therapy, or Brachytherapy in Men Without Comorbidity SO EUROPEAN UROLOGY LA English DT Article DE Prostatic neoplasms; Prostatectomy; Radiation therapy; Comorbidity; Comparative effectiveness research ID ANDROGEN-DEPRIVATION THERAPY; QUALITY-OF-LIFE; SECONDARY MALIGNANCIES; RISK; OUTCOMES; DEATH; RADIOTHERAPY; SURVIVAL; SURGERY; SUPPRESSION AB Background: Medical comorbidity is a confounding factor in prostate cancer (PCa) treatment selection and mortality. Large-scale comparative evaluation of PCa mortality (PCM) and overall mortality (OM) restricted to men without comorbidity at the time of treatment has not been performed. Objective: To evaluate PCM and OM in men with no recorded comorbidity treated with radical prostatectomy (RP), external-beam radiation therapy (EBRT), or brachytherapy (BT). Design, setting, and participants: Data from 10 361 men with localized PCa treated from 1995 to 2007 at two academic centers in the United States were prospectively obtained at diagnosis and retrospectively reviewed. We identified 6692 men with no recorded comorbidity on a validated comorbidity index. Median follow-up after treatment was 7.2 yr. Intervention: Treatment with RP in 4459 men, EBRT in 1261 men, or BT in 972 men. Outcome measurements and statistical analysis: Univariate and multivariate Cox proportional hazards regression analysis, including propensity score adjustment, compared PCM and OM for EBRT and BT relative to RP as reference treatment category. PCM was also evaluated by competing risks analysis. Results and limitations: Using Cox analysis, EBRT was associated with an increase in PCM compared with RP (hazard ratio [HR]: 1.66; 95% confidence interval [CI], 1.05-2.63), while there was no statistically significant increase with BT (HR: 1.83; 95% CI, 0.88-3.82). Using competing risks analysis, the benefit of RP remained but was no longer statistically significant for EBRT (HR: 1.55; 95% CI, 0.92-2.60) or BT (HR: 1.66; 95% CI, 0.79-3.46). In comparison with RP, both EBRT (HR: 1.71; 95% CI, 1.40-2.08) and BT (HR: 1.78; 95% CI, 1.37-2.31) were associated with increased OM. Conclusions: In a large multicenter series of men without recorded comorbidity, both forms of radiation therapy were associated with an increase in OM compared with surgery, but there were no differences in PCM when evaluated by competing risks analysis. These findings may result from an imbalance of confounders or differences in mortality related to primary or salvage therapy. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Nepple, Kenneth G.; Kallogjeri, Dorina; Michalski, Jeff; Grubb, Robert L., III; Strope, Seth A.; Haslag-Minoff, Jennifer; Piccirillo, Jay F.; Kibel, Adam S.] Washington Univ, Sch Med, St Louis, MO USA. [Nepple, Kenneth G.] Univ Iowa, Iowa City, IA 52242 USA. [Stephenson, Andrew J.; Ciezki, Jay P.; Klein, Eric A.; Reddy, Chandana A.; Yu, Changhong; Kattan, Michael W.] Cleveland Clin, Cleveland, OH 44106 USA. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nepple, KG (reprint author), Univ Iowa, Dept Urol, 200 Hawkins Dr,3 RCP, Iowa City, IA 52242 USA. EM kenneth-nepple@uiowa.edu OI Strope, Seth/0000-0002-5176-1550 FU St. Louis Men's Group Against Cancer; David H. Nickerson Foundation; Washington University Comparative Effectiveness Research Mentored Career Development Award KM1 (NIH) [1KM1CA156708-01] FX This work was supported in part by the St. Louis Men's Group Against Cancer and the David H. Nickerson Foundation.; Kenneth G. Nepple certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Kenneth G. Nepple was supported by a Washington University Comparative Effectiveness Research Mentored Career Development Award KM1 (NIH Grant Number 1KM1CA156708-01). NR 34 TC 31 Z9 31 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD SEP PY 2013 VL 64 IS 3 BP 372 EP 378 DI 10.1016/j.eururo.2013.03.005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 211VF UT WOS:000323938700017 PM 23506834 ER PT J AU Fine, DH Markowitz, K Fairlie, K Tischio-Bereski, D Ferrendiz, J Furgang, D Paster, BJ Dewhirst, FE AF Fine, Daniel H. Markowitz, Kenneth Fairlie, Karen Tischio-Bereski, Debbie Ferrendiz, Javier Furgang, David Paster, Bruce J. Dewhirst, Floyd E. TI A Consortium of Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, and Filifactor alocis Is Present in Sites Prior to Bone Loss in a Longitudinal Study of Localized Aggressive Periodontitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID EARLY-ONSET PERIODONTITIS; HIGHLY TOXIC CLONE; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; JUVENILE PERIODONTITIS; BACTERIAL DIVERSITY; DISEASE; VIRULENCE; ADOLESCENTS; CHILDREN; IDENTIFICATION AB Aggregatibacter actinomycetemcomitans-induced localized aggressive periodontitis (LAP) in African-American adolescents has been documented but is poorly understood. Two thousand fifty-eight adolescents aged 11 to 17 years were screened for their periodontal status and the presence of A. actinomycetemcomitans in their oral cavity. Seventy-one A. actinomycetemcomitans-negative and 63 A. actinomycetemcomitans-positive periodontally healthy subjects were enrolled, sampled, examined, and radio-graphed yearly for 3 years. Gingival and periodontal pocket depth and attachment levels were recorded. Disease presentation was characterized by bone loss (BL). Subgingival sites were sampled every 6 months to assess (i) the role of A. actinomycetemcomitans in BL and (ii) the association of A. actinomycetemcomitans and other microbes in their relationships to BL. Sixteen of 63 subjects with A. actinomycetemcomitans developed BL (the other 47 subjects with A. actinomycetemcomitans had no BL). No A. actinomycetemcomitans-negative subjects developed BL. Human oral microbe identification microarray (HOMIM) was used for subgingival microbial assessment. On a subject level, pooled data from A. actinomycetemcomitans-positive subjects who remained healthy had higher prevalences of Streptococcus and Actinomyces species, while A. actinomycetemcomitans-positive subjects with BL had higher prevalences of Parvimonas micra, Filifactor alocis, A. actinomycetemcomitans, and Peptostreptococcus sp. human oral taxon 113 (HOT-113). At vulnerable sites, A. actinomycetemcomitans, Streptococcus parasanguinis, and F. alocis levels were elevated prior to BL. In cases where the three-organism consortium (versus A. actinomycetemcomitans alone) was detected, the specificity for detecting sites of future BL increased from 62% to 99%, with a sensitivity of 89%. We conclude that detecting the presence of A. actinomycetemcomitans, S. parasanguinis, and F. alocis together indicates sites of future BL in LAP. A synergistic interaction of this consortium in LAP causation is possible and is the subject of ongoing research. C1 [Fine, Daniel H.; Markowitz, Kenneth; Fairlie, Karen; Tischio-Bereski, Debbie; Ferrendiz, Javier; Furgang, David] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Oral Biol, Newark, NJ 07103 USA. [Paster, Bruce J.; Dewhirst, Floyd E.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Paster, Bruce J.; Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Fine, DH (reprint author), Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Oral Biol, Newark, NJ 07103 USA. EM finedh@umdnj.edu FU National Institute of Dental and Craniofacial Research of the National Institutes of Health [R01DE017968, R37DE016937] 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 no. R01DE017968 (to D.H.F.) and R37DE016937 (to F.E.D.). NR 46 TC 23 Z9 23 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2013 VL 51 IS 9 BP 2850 EP 2861 DI 10.1128/JCM.00729-13 PG 12 WC Microbiology SC Microbiology GA 202KL UT WOS:000323214200008 PM 23784124 ER PT J AU Branda, JA Markham, RP Garner, CD Rychert, JA Ferraro, MJ AF Branda, John A. Markham, Rachelle P. Garner, Cherilyn D. Rychert, Jenna A. Ferraro, Mary Jane TI Performance of the Vitek MS v2.0 System in Distinguishing Streptococcus pneumoniae from Nonpneumococcal Species of the Streptococcus mitis Group SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FLIGHT MASS-SPECTROMETRY; DESORPTION IONIZATION-TIME; LASER-DESORPTION/IONIZATION-TIME; COAGULASE-NEGATIVE STAPHYLOCOCCI; ALPHA-HEMOLYTIC STREPTOCOCCI; VIRIDANS GROUP STREPTOCOCCI; ANAEROBIC-BACTERIA; MICROBIOLOGY LABORATORIES; PHENOTYPIC METHODS; IDENTIFICATION AB The Vitek MS v2.0 matrix-assisted laser desorption ionization-time of flight mass spectrometry system accurately distinguished Streptococcus pneumoniae from nonpneumococcal S. mitis group species. Only 1 of 116 nonpneumococcal isolates (<1%) was misidentified as S. pneumoniae. None of 95 pneumococcal isolates was misidentified. This method provides a rapid, simple means of discriminating among these challenging organisms. C1 [Branda, John A.; Markham, Rachelle P.; Rychert, Jenna A.; Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, John A.; Rychert, Jenna A.; Ferraro, Mary Jane] Harvard Univ, Sch Med, Boston, MA USA. [Garner, Cherilyn D.] BioMerieux Inc, R&D Microbiol, Hazelwood, MO USA. RP Branda, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM jbranda@partners.org FU bioMerieux, Inc.; bioMerieux; Becton FX This work was funded by bioMerieux, Inc. M.J.F., J.A.B., and J.A.R. have received research funding from bioMerieux and Becton, Dickinson for other research investigations but do not have a financial interest in either company. C.D.G. is employed by bioMerieux, Inc., in the research and development division. NR 37 TC 17 Z9 18 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2013 VL 51 IS 9 BP 3079 EP 3082 DI 10.1128/JCM.00824-13 PG 4 WC Microbiology SC Microbiology GA 202KL UT WOS:000323214200044 PM 23784130 ER PT J AU Walcott, BP Berkhemer, OA Leslie-Mazwi, TM Chandra, RV Ogilvy, CS Yoo, AJ AF Walcott, Brian P. Berkhemer, Olvert A. Leslie-Mazwi, Thabele M. Chandra, Ronil V. Ogilvy, Christopher S. Yoo, Albert J. TI Multimodal endovascular treatment of a vertebrovertebral fistula presenting with subarachnoid hemorrhage and hydrocephalus SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Cervical; Endovascular; Hydrocephalus; Stroke; Subarachnoid; Vertebral artery; Vertebrovertebral fistula ID DURAL ARTERIOVENOUS-FISTULAS; INDOCYANINE GREEN VIDEOANGIOGRAPHY; ONYX EMBOLIZATION; VERTEBRAL ARTERY; SURGERY; CLASSIFICATION; MALFORMATIONS; ANGIOGRAPHY AB Vertebrovertebral fistulae are rare vascular malformations that uncommonly can rupture to present clinically as intracranial subarachnoid hemorrhage. We report a 69-year-old man presenting following spontaneous apoplectic collapse. Initial workup revealed diffuse, intracranial subarachnoid hemorrhage, intraventricular hemorrhage and hydrocephalus. However, the etiology was not apparent on CT angiography of the head. Catheter-based angiography was performed, demonstrating a single-hole, high-flow vertebrovertebral fistula, arising from the V2 segment and decompressing into both cervical and skull base venous structures. Definitive treatment consisted of endovascular fistula obliteration with a combination of coil and liquid embolic material. The patient made a full neurological recovery. High cervical and skull base fistulae are rare causes of intracranial hemorrhage; endovascular treatment is effective at disconnection of the arteriovenous shunt. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Berkhemer, Olvert A.; Leslie-Mazwi, Thabele M.; Chandra, Ronil V.; Ogilvy, Christopher S.; Yoo, Albert J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Walcott, Brian P.; Berkhemer, Olvert A.; Leslie-Mazwi, Thabele M.; Chandra, Ronil V.; Ogilvy, Christopher S.; Yoo, Albert J.] Massachusetts Gen Hosp, Div Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R25 NS065743] NR 29 TC 0 Z9 1 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2013 VL 20 IS 9 BP 1295 EP 1298 DI 10.1016/j.jocn.2013.01.006 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 212TP UT WOS:000324006000023 PM 23830589 ER PT J AU Uzi, D Barda, L Scaiewicz, V Mills, M Mueller, T Gonzalez-Rodriguez, A Valverde, AM Iwawaki, T Nahmias, Y Xavier, R Chung, RT Tirosh, B Shibolet, O AF Uzi, Dotan Barda, Liran Scaiewicz, Viviana Mills, Maya Mueller, Tobias Gonzalez-Rodriguez, Agueda Valverde, Angela M. Iwawaki, Takao Nahmias, Yaacov Xavier, Ramnik Chung, Ray T. Tirosh, Boaz Shibolet, Oren TI CHOP is a critical regulator of acetaminophen-induced hepatotoxicity SO JOURNAL OF HEPATOLOGY LA English DT Article DE Endoplasmic reticulum stress; Unfolded protein response; Acetaminophen hepatotoxicity; Drug induced liver injury ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ACUTE LIVER-FAILURE; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; GENE-EXPRESSION; MESSENGER-RNA; UNITED-STATES; ER STRESS; MICE AB Background & Aims: The liver is a major site of drug metabolism and elimination and as such is susceptible to drug toxicity. Drug induced liver injury is a leading cause of acute liver injury, of which acetaminophen (APAP) is the most frequent causative agent. APAP toxicity is initiated by its toxic metabolite NAPQI. However, downstream mechanisms underlying APAP induced cell death are still unclear. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have recently emerged as major regulators of metabolic homeostasis. UPR regulation of the transcription repressor CHOP promotes cell death. We analyzed the role of UPR and CHOP in mediating APAP hepatotoxicity. Methods: A toxic dose of APAP was orally administered to wild type (wt) and CHOP knockout (KO) mice and damage mechanisms were assessed. Results: CHOP KO mice were protected from APAP induced damage and exhibited decreased liver necrosis and increased survival. APAP metabolism in CHOP KO mice was undisturbed and glutathione was depleted at similar kinetics to wt. ER stress and UPR activation were overtly seen 12 h following APAP administration, a time that coincided with strong upregulation of CHOP. Remarkably, CHOP KO but not wt mice exhibited hepatocyte proliferation at sites of necrosis. In vitro, large T immortalized CHOP KO hepatocytes were protected from APAP toxicity in comparison to wt control cells. Conclusions: CHOP upregulation during APAP induced liver injury compromises hepatocyte survival in various mechanisms, in part by curtailing the regeneration phase following liver damage. Thus, CHOP plays a pro-damage role in response to APAP intoxication. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved. C1 [Uzi, Dotan; Scaiewicz, Viviana; Tirosh, Boaz] Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Inst Drug Res, Jerusalem, Israel. [Barda, Liran; Mills, Maya] Hadassah Hebrew Univ Med Ctr, Div Med, Liver Unit, Jerusalem, Israel. [Mueller, Tobias] Charite, CVK, Med Klin MS Hepatol & Gastroenterol, D-13353 Berlin, Germany. [Gonzalez-Rodriguez, Agueda; Valverde, Angela M.] Inst Biomed Alberto Sols CSIC UAM, Madrid 28029, Spain. [Gonzalez-Rodriguez, Agueda; Valverde, Angela M.] ISCIII, Spanish Biomed Res Ctr Diabet & Associated Metab, Barcelona, Spain. [Iwawaki, Takao] RIKEN, Wako, Saitama, Japan. [Iwawaki, Takao] Gunma Univ, Adv Sci Res Leaders Dev Unit, Gunma, Japan. [Nahmias, Yaacov] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Rachel & Selim Benin Sch Comp Sci & Engn, Ctr Bioengn, Jerusalem, Israel. [Xavier, Ramnik; Chung, Ray T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Xavier, Ramnik; Chung, Ray T.] Harvard Univ, Sch Med, Boston, MA USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Shibolet, Oren] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Gastroenterol, Liver Unit, IL-69978 Tel Aviv, Israel. [Shibolet, Oren] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Shibolet, O (reprint author), Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Gastroenterol, Liver Unit, IL-69978 Tel Aviv, Israel. EM orensh@tasmc.health.gov.il RI Nahmias, Yaakov/H-4725-2013; Gonzalez-Rodroguez, Agueda/D-7651-2012 OI Gonzalez-Rodroguez, Agueda/0000-0001-6559-0847 FU MINECO, Spain [SAF2012-33283]; Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), ISCIII; Comunidad de Madrid [S2010/BMD-2423]; EFSD/Amylin Programme; Morasha Program of Israel Science Foundation [1668/08]; BSF [2007083]; Israel Science Foundation [78/09] FX This research was supported by SAF2012-33283 (MINECO, Spain) and Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), ISCIII and Comunidad de Madrid S2010/BMD-2423 and EFSD/Amylin Programme 2011 to AMV Spain to AMV. The Morasha Program of Israel Science Foundation (grant No. 1668/08) to OS, by the BSF (grant No. 2007083) to OS and RX, and by the Israel Science Foundation (grant 78/09) to BT. NR 48 TC 33 Z9 34 U1 0 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2013 VL 59 IS 3 BP 495 EP 503 DI 10.1016/j.jhep.2013.04.024 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 207LT UT WOS:000323602000018 PM 23665281 ER PT J AU Chan, KE Thadhani, RI Maddux, FW AF Chan, Kevin E. Thadhani, Ravi I. Maddux, Franklin W. TI No difference in bleeding risk between subcutaneous enoxaparin and heparin for thromboprophylaxis in end-stage renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE anticoagulation; dialysis; thromboprophylaxis ID MOLECULAR-WEIGHT HEPARIN; THROMBIN GENERATION TIME; VENOUS THROMBOEMBOLISM; MEDICAL PATIENTS; HEMODIALYSIS; ANTICOAGULANT; METAANALYSIS; PHARMACOKINETICS; DYSFUNCTION; INHIBITION AB Enoxaparin, a low-molecular-weight form of heparin, is not approved for use in dialysis patients in the United States, because it is eliminated through the kidneys and could therefore accumulate and cause inadvertent bleeding. Accordingly, it is unknown if enoxaparin is as safe to prescribe as subcutaneous heparin for thromboprophylaxis in patients with chronic renal failure. Here we conducted a retrospective comparative effectiveness study in a large population of chronic maintenance dialysis patients initiated with subcutaneous injections of enoxaparin or heparin for thromboprophylaxis. The primary study end point was hospitalization or death related to bleeding, with a secondary end point of venous thromboembolism. Among 7721 dialysis patients started on subcutaneous enoxaparin or heparin at doses for thromboprophylaxis, the crude rate for bleeding requiring hospitalization or resulting in death was 15.2 (95% confidence interval (CI) 12.7-18.2) events per 100 patient-years in the enoxaparin group, which did not differ from the heparin group in which the crude rate was 16.2 (95% CI 14.0-18.7) events per 100 patient-years. In risk factor-adjusted Poisson models, enoxaparin was not associated with more bleeding in comparison to heparin (risk ratio, 0.98; 95% CI 0.78-1.23). The risk of venous thromboembolism was not associatively worse with enoxaparin (risk ratio, 0.77; 95% CI 0.49-1.22). Thus, in dialysis patients, daily enoxaparin for thromboprophylaxis was not associated with increased serious bleeding or less effective compared to subcutaneous heparin. C1 [Chan, Kevin E.; Maddux, Franklin W.] Fresenius Med Care North Amer, Div Clin Res, Waltham, MA 02451 USA. [Chan, Kevin E.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Chan, KE (reprint author), Fresenius Med Care North Amer, Div Clin Res, 920 Winter St, Waltham, MA 02451 USA. EM kevin.chan@fmc-na.com FU NIEHS NIH HHS [P30 ES002109] NR 31 TC 6 Z9 6 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2013 VL 84 IS 3 BP 555 EP 561 DI 10.1038/ki.2013.152 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 209KP UT WOS:000323755300018 PM 23677243 ER PT J AU Kreissman, SG Seeger, RC Matthay, KK London, WB Sposto, R Grupp, SA Haas-Kogan, DA LaQuaglia, MP Yu, AL Diller, L Buxton, A Park, JR Cohn, SL Maris, JM Reynolds, CP Villablanca, JG AF Kreissman, Susan G. Seeger, Robert C. Matthay, Katherine K. London, Wendy B. Sposto, Richard Grupp, Stephan A. Haas-Kogan, Daphne A. LaQuaglia, Michael P. Yu, Alice L. Diller, Lisa Buxton, Allen Park, Julie R. Cohn, Susan L. Maris, John M. Reynolds, C. Patrick Villablanca, Judith G. TI Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID CHILDRENS ONCOLOGY GROUP; STAGE-IV NEUROBLASTOMA; BONE-MARROW; INDUCTION CHEMOTHERAPY; PEDIATRIC-ONCOLOGY; MOLECULAR RESPONSE; FRENCH-SOCIETY; THERAPY; DISEASE; CONTAMINATION AB Background Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma. Currently, peripheral blood stem cells (PBSC) are infused after myeloablative therapy, but the effect of purging is unknown. We did a randomised study of tumour-selective PBSC purging in stem-cell transplantation for patients with high-risk neuroblastoma. Methods Between March 16, 2001, and Feb 24, 2006, children and young adults (<30 years) with high-risk neuroblastoma were randomly assigned at diagnosis by a web-based system (in a 1:1 ratio) to receive either non-purged or immunomagnetically purged PBSC. Randomisation was done in blocks stratified by International Neuroblastoma Staging System stage, age, MYCN status, and International Neuroblastoma Pathology classification. Patients and treating physicians were not masked to treatment assignment. All patients were treated with six cycles of induction chemotherapy, myeloablative consolidation, and radiation therapy to the primary tumour site plus meta-iodobenzylguanidine avid metastases present before myeloablative therapy, followed by oral isotretinoin. PBSC collection was done after two induction cycles. For purging, PBSC were mixed with carbonyl iron and phagocytic cells removed with samarium cobalt magnets. Remaining cells were mixed with immunomagnetic beads prepared with five monoclonal antibodies targeting neuroblastoma cell surface antigens and attached cells were removed using samarium cobalt magnets. Patients underwent autologous stem-cell transplantation with PBSC as randomly assigned after six cycles of induction therapy. The primary endpoint was event-free survival and was analysed by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT00004188. Findings 495 patients were enrolled, of whom 486 were randomly assigned to treatment: 243 patients to receive non-purged PBSC and 243 to received purged PBSC. PBSC were collected from 229 patients from the purged group and 236 patients from the non-purged group, and 180 patients from the purged group and 192 from the non-purged group received transplant. 5-year event-free survival was 40% (95% CI 33-46) in the purged group versus 36% (30-42) in the non-purged group (p = 0.77); 5-year overall survival was 50% (95% CI 43-56) in the purged group compared with 51% (44-57) in the non-purged group (p = 0.81). Toxic deaths occurred in 15 patients during induction (eight in the purged group and seven in the non-purged group) and 12 during consolidation (eight in the purged group and four in the non-purged group). The most common adverse event reported was grade 3 or worse stomatitis during both induction (87 of 242 patients in the purged group and 93 of 243 patients in the non-purged group) and consolidation (131 of 177 in the purged group vs 145 of 191 in the non-purged group). Serious adverse events during induction were grade 3 or higher decreased cardiac function (four of 242 in the purged group and five of 243 in the non-purged group) and elevated creatinine (five of 242 in the purged group and six of 243 non-purged group) and during consolidation were sinusoidal obstructive syndrome (12 of 177 in the purged group and 17 of 191 in the non-purged group), acute vascular leak (11 of 177 in the purged group and nine of 191 in the non-purged group), and decreased cardiac function (one of 177 in the purged group and four of 191 in the non-purged group). Interpretation Immunomagnetic purging of PBSC for autologous stem-cell transplantation did not improve outcome, perhaps because of incomplete purging or residual tumour in patients. Non-purged PBSC are acceptable for support of myeloablative therapy of high-risk neuroblastoma. C1 [Kreissman, Susan G.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Seeger, Robert C.; Sposto, Richard; Villablanca, Judith G.] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Matthay, Katherine K.; Haas-Kogan, Daphne A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [London, Wendy B.; Diller, Lisa] Boston Childrens Hosp, Dana Farber Harvard Canc Ctr, Boston, MA USA. [London, Wendy B.; Buxton, Allen] Childrens Oncol Grp Stat & Data Ctr, Monrovia, CA USA. [Grupp, Stephan A.; Maris, John M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Grupp, Stephan A.; Maris, John M.] Univ Penn, Philadelphia, PA 19104 USA. [LaQuaglia, Michael P.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Yu, Alice L.] Rady Childrens Hosp, San Diego, CA USA. [Park, Julie R.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Cohn, Susan L.] Univ Chicago, Chicago, IL 60637 USA. [Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. RP Kreissman, SG (reprint author), Duke Univ, Med Ctr, Box 102382,Hanes House,330 Trent Dr, Durham, NC 27710 USA. EM susan.kreissman@duke.edu OI Reynolds, C. Patrick/0000-0002-2827-8536; Cohn, Susan/0000-0001-5749-7650 FU COG Group Chair's grant [U10-CA98543]; COG Statistics and Data Center [U10-CA98413, U10-CA37379, U10-CA30969, U10-CA29139, R33-CA152809-01]; Alex's Lemonade Stand Foundation FX This work was supported by U10-CA98543 COG Group Chair's grant, COG Statistics and Data Center grants: U10-CA98413, U10-CA37379, U10-CA30969, and U10-CA29139; R33-CA152809-01, Alex's Lemonade Stand Foundation. Immunomagnetic bead purging of PBSC was done under a US Food and Drug Administration (FDA) Investigational New Device exemption (IDE) BB-IDE 2259 with periodic review done as required by law. Third party payers were responsible for the cost of PBSC purging as allowed under IDE BB-IDE 2259. We thank the Children's Hospital of Los Angeles staff in the hematopoietic stem cell processing/purging laboratory (Carolyn Billups, Jin-Hua Min, Maybelle Sim, and Robert Torres), the immunocytology laboratory (Rich Gallego, Alfonso Parra), and the TLDA laboratory (Cathy Wei Yao Liu and Betty Liu) for their essential contributions, and Peter Wakamatsu for his statistical and database efforts. We also thank the COG staff, CRA, nursing and pharmacy committee members for their contributions: Dina Willis (COG Statistics and Data Center), Sally Jones (Washington University School of Medicine, MO, USA), Casey Hook (University of Minnesota Medical Center, Fairview, MN, USA), and John T Wiernikowski (McMaster University, ON, Canada) for providing technical and pharmaceutical assistance. NR 29 TC 63 Z9 65 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2013 VL 14 IS 10 BP 999 EP 1008 DI 10.1016/S1470-2045(13)70309-7 PG 10 WC Oncology SC Oncology GA 211WM UT WOS:000323942500046 PM 23890779 ER PT J AU Lin, NU Lee, EQ Aoyama, H Barani, IJ Baumert, BG Brown, PD Camidge, DR Chang, SM Dancey, J Gaspar, LE Harris, GJ Hodi, FS Kalkanis, SN Lamborn, KR Linskey, ME Macdonald, DR Margolin, K Mehta, MP Schiff, D Soffietti, R Suh, JH van den Bent, MJ Vogelbaum, MA Wefel, JS Wen, PY AF Lin, Nancy U. Lee, Eudocia Q. Aoyama, Hidefumi Barani, Igor J. Baumert, Brigitta G. Brown, Paul D. Camidge, D. Ross Chang, Susan M. Dancey, Janet Gaspar, Laurie E. Harris, Gordon J. Hodi, F. Stephen Kalkanis, Steven N. Lambom, Kathleen R. Linskey, Mark E. Macdonald, David R. Margolin, Kim Mehta, Minesh P. Schiff, David Soffietti, Riccardo Suh, John H. van den Bent, Martin J. Vogelbaum, Michael A. Wefel, Jeffrey S. Wen, Patrick Y. CA Response Assessment Neuro Oncol RA TI Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group SO LANCET ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; NERVOUS-SYSTEM METASTASES; PHASE-II TRIAL; GAMMA-KNIFE RADIOSURGERY; NEGATIVE BREAST-CANCER; RADIATION-THERAPY; CEREBRAL METASTASES; RANDOMIZED-TRIAL; ONCOLOGY-GROUP; WORKING GROUP AB Therapeutic outcomes for patients with brain metastases need to improve. A critical review of trials specifically addressing brain metastases shows key issues that could prevent acceptance of results by regulatory agencies, including enrolment of heterogeneous groups of patients and varying definitions of clinical endpoints. Considerations specific to disease, modality, and treatment are not consistently addressed. Additionally, the schedule of CNS imaging and consequences of detection of new or progressive brain metastases in trials mainly exploring the extra-CNS activity of systemic drugs are highly variable. The Response Assessment in Neuro-Oncology (RANO) working group is an independent, international, collaborative effort to improve the design of trials in patients with brain tumours. In this two-part series, we review the state of clinical trials of brain metastases and suggest a consensus recommendation for the development of criteria for future clinical trials. C1 [Lin, Nancy U.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lee, Eudocia Q.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neuro Oncol, Boston, MA 02215 USA. [Aoyama, Hidefumi] Niigata Univ, Grad Sch Med & Dent Sci, Dept Radiol, Niigata, Japan. [Barani, Igor J.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Chang, Susan M.; Lambom, Kathleen R.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Chang, Susan M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Baumert, Brigitta G.] Maastricht Univ, Ctr Clin, Dept Radiat Oncol, Maastricht, Netherlands. [Brown, Paul D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Wefel, Jeffrey S.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Camidge, D. Ross] Univ Colorado, Div Med Oncol, Sch Med, Denver, CO USA. [Dancey, Janet] Queens Univ, Fac Hlth Sci, Kingston, ON, Canada. [Dancey, Janet] Queens Univ, Ontario Inst Canc Res, Kingston, ON, Canada. [Gaspar, Laurie E.] Univ Colorado, Dept Radiat Oncol, Aurora, CO USA. [Harris, Gordon J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. [Linskey, Mark E.] Univ Calif Irvine, Dept Neurol Surg, Irvine, CA USA. [Macdonald, David R.] Univ Western Ontario, Dept Oncol, London Hlth Sci Ctr, London, ON, Canada. [Margolin, Kim] Univ Washington, Sch Med, Div Oncol, Seattle Canc Care Alliance, Seattle, WA USA. [Mehta, Minesh P.] Univ Maryland, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Schiff, David] Univ Virginia, Div Neuro Oncol, Charlottesville, VA USA. [Soffietti, Riccardo] Univ Turin, Dept Neurol, Turin, Italy. [Soffietti, Riccardo] Univ Turin, Dept Neuro Oncol, Turin, Italy. [Suh, John H.; Vogelbaum, Michael A.] Case Western Reserve Univ, Lerner Coll Med, Rose Ella Burkhardt Brain Tumor & Neuro Oncol Ctr, Cleveland Clin, Cleveland, OH 44106 USA. [van den Bent, Martin J.] Erasmus Univ, Inst Canc, Rotterdam, Netherlands. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM nlin@partners.org RI Aoyama, Hidefumi/D-3635-2016 OI Aoyama, Hidefumi/0000-0002-8437-7491 FU Breast Cancer Research Foundation FX This work was supported in part by the Breast Cancer Research Foundation (grant to NUL), but this organisation did not directly influence the authors in the writing of this report or the decision to submit it for publication. We thank Raymond Huang, Brigham and Women's Hospital, Boston, MA, USA, and Nils Arvold, Dana-Farber Cancer Institute, Boston, MA, USA, for providing the figures. NR 76 TC 46 Z9 46 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2013 VL 14 IS 10 BP E396 EP E406 PG 11 WC Oncology SC Oncology GA 211WM UT WOS:000323942500015 PM 23993384 ER PT J AU Lin, NU Wefel, JRS Lee, EQ Schiff, D van den Bent, MJ Soffietti, R Suh, JH Vogelbaum, MA Mehta, MP Dancey, J Linskey, ME Camidge, DR Aoyama, H Brown, PD Chang, SM Kalkanis, SN Barani, IJ Baumert, BG Gaspar, LE Hodi, FS Macdonald, DR Wen, PY AF Lin, Nancy U. Wefel, Jeff Rey S. Lee, Eudocia Q. Schiff, David van den Bent, Martin J. Soffietti, Riccardo Suh, John H. Vogelbaum, Michael A. Mehta, Minesh P. Dancey, Janet Linskey, Mark E. Camidge, D. Ross Aoyama, Hidefumi Brown, Paul D. Chang, Susan M. Kalkanis, Steven N. Barani, Igor J. Baumert, Brigitta G. Gaspar, Laurie E. Hodi, F. Stephen Macdonald, David R. Wen, Patrick Y. CA Response Assessment Neuro Oncol RA TI Challenges relating to solid tumour brain metastases in clinical trials, part 2: neurocognitive, neurological, and quality-of-life outcomes. A report from the RANO group SO LANCET ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; PROPHYLACTIC CRANIAL IRRADIATION; PHASE-III TRIAL; RANDOMIZED CONTROLLED-TRIAL; RADIATION-THERAPY; BREAST-CANCER; STEREOTACTIC RADIOSURGERY; MOTEXAFIN GADOLINIUM; END-POINTS; SURGICAL RESECTION AB Neurocognitive function, neurological symptoms, functional independence, and health-related quality of life are major concerns for patients with brain metastases. The inclusion of these endpoints in trials of brain metastases and the methods by which these measures are assessed vary substantially. If functional independence or health-related quality of life are planned as key study outcomes, then the reliability and validity of these endpoints can be crucial because methodological issues might affect the interpretation and acceptance of findings. The Response Assessment in Neuro-Oncology (RANO) working group is an independent, international, and collaborative effort to improve the design of clinical trials in patients with brain tumours. In this report, the second in a two-part series, we review clinical trials of brain metastases in relation to measures of clinical benefit and provide a framework for the design and conduct of future trials. C1 [Lin, Nancy U.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lee, Eudocia Q.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neuro Oncol, Boston, MA 02215 USA. [Wefel, Jeff Rey S.; Brown, Paul D.] Univ Texas MD Anderson Canc Ctr, Dept Neuro Oncol, Houston, TX 77030 USA. [Schiff, David] Univ Virginia, Div Neuro Oncol, Charlottesville, VA USA. [van den Bent, Martin J.] Erasmus Univ, Inst Canc, Rotterdam, Netherlands. [Soffietti, Riccardo] Univ Turin, Dept Neurol, Turin, Italy. [Soffietti, Riccardo] Univ Turin, Dept Neuro Oncol, Turin, Italy. [Suh, John H.; Vogelbaum, Michael A.] Case Western Reserve Univ, Lerner Coll Med, Rose Ella Burkhardt Brain Tumor & Neuro Oncol Ctr, Cleveland Clin, Cleveland, OH 44106 USA. [Mehta, Minesh P.] Univ Maryland, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Dancey, Janet] Queens Univ, Fac Hlth Sci, Kingston, ON, Canada. [Dancey, Janet] Queens Univ, Ontario Inst Canc Res, Kingston, ON, Canada. [Linskey, Mark E.] Univ Calif Irvine, Dept Neurol Surg, Orange, CA 92668 USA. [Macdonald, David R.] Univ Colorado, Sch Med, Div Med Oncol, Denver, CO 80202 USA. [Aoyama, Hidefumi] Niigata Univ, Dept Radiol, Grad Sch Med & Dent Sci, Niigata, Japan. [Barani, Igor J.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Chang, Susan M.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Chang, Susan M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. [Baumert, Brigitta G.] Maastricht Univ, Ctr Clin, Dept Radiat Oncol, Maastricht, Netherlands. [Gaspar, Laurie E.] Univ Colorado, Aurora, CO USA. [Macdonald, David R.] Univ Western Ontario, Dept Oncol, London Hlth Sci Ctr, London, ON, Canada. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM nlin@partners.org RI Aoyama, Hidefumi/D-3635-2016 OI Aoyama, Hidefumi/0000-0002-8437-7491 FU Breast Cancer Research Foundation FX This work was supported in part by the Breast Cancer Research Foundation (grant to NUL), but the organisation did not directly influence the authors in the writing of this report or the decision to submit it for publication. NR 70 TC 34 Z9 35 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2013 VL 14 IS 10 BP E407 EP E416 PG 10 WC Oncology SC Oncology GA 211WM UT WOS:000323942500016 PM 23993385 ER PT J AU Wala, J Craft, D Paly, J Zietman, A Efstathiou, J AF Wala, Jeremiah Craft, David Paly, Jon Zietman, Anthony Efstathiou, Jason TI Maximizing dosimetric benefits of IMRT in the treatment of localized prostate cancer through multicriteria optimization planning SO MEDICAL DOSIMETRY LA English DT Article DE IMRT; Multicriteria optimization; Prostate ID INTENSITY-MODULATED RADIOTHERAPY; CONFORMAL RADIATION-THERAPY; DOSE-ESCALATION; MULTIOBJECTIVE OPTIMIZATION; RANDOMIZED-TRIAL; ADENOCARCINOMA; ALGORITHM; SURFACES AB We examine the quality of plans created using multicriteria optimization (MCO) treatment planning in intensity-modulated radiation therapy (IMRT) in treatment of localized prostate cancer. Nine random cases of patients receiving IMRT to the prostate were selected. Each case was associated with a clinically approved plan created using Corvus. The cases were replanned using MCO-based planning in RayStation. Dose-volume histogram data from both planning systems were presented to 2 radiation oncologists in a blinded evaluation, and were compared at a number of dose-volume points. Both physicians rated all 9 MCO plans as superior to the clinically approved plans (p < 10(-5)). Target coverage was equivalent (p = 0.81). Maximum doses to the prostate and bladder and the V50 and V70 to the anterior rectum were reduced in all MCO plans (p < 0.05). Treatment planning time with MCO took approximately 60 minutes per case. MCO-based planning for prostate IMRT is efficient and produces high-quality plans with good target homogeneity and sparing of the anterior rectum, bladder, and femoral heads, without sacrificing target coverage. (C) 2013 American Association of Medical Dosimetrists. C1 [Wala, Jeremiah; Craft, David; Zietman, Anthony; Efstathiou, Jason] Harvard Univ, Sch Med, Boston, MA USA. [Wala, Jeremiah; Craft, David; Paly, Jon; Zietman, Anthony; Efstathiou, Jason] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Efstathiou, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox Bldg Lower Level,100 Blossom St, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 26 TC 8 Z9 10 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 J9 MED DOSIM JI Med. Dosim. PD FAL PY 2013 VL 38 IS 3 BP 298 EP 303 DI 10.1016/j.meddos.2013.02.012 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 199WA UT WOS:000323025000013 PM 23540492 ER PT J AU Christodouleas, JP Tang, SK Susil, RC McNutt, TR Song, DY Bekelman, J Deville, C Vapiwala, N DeWeese, TL Lu, HM Both, S AF Christodouleas, John P. Tang, Shikui Susil, Robert C. McNutt, Todd R. Song, Danny Y. Bekelman, Justin Deville, Curtiland Vapiwala, Neha DeWeese, Theodore L. Lu, Hsiao-Ming Both, Stefan TI The effect of anterior proton beams in the setting of a prostate-rectum spacer SO MEDICAL DOSIMETRY LA English DT Article DE Spacer; Proton therapy; Anterior beams; Prostate-rectum spacer AB Studies suggest that anterior beams with in vivo range verification would improve rectal dosimetry in proton therapy for prostate cancer. We investigated whether prostate-rectum spacers would enhance or diminish the benefits of anterior proton beams in these treatments. Twenty milliliters of hydrogel was injected between the prostate and rectum of a cadaver using a transperineal approach. Computed tomography (CT) and magnetic resonance (MR) images were used to generate 7 uniform scanning (US) and 7 single-field uniform dose pencil-beam scanning (PBS) plans with different beam arrangements. Pearson correlations were calculated between rectal, bladder, and femoral head dosimetric outcomes and beam arrangement anterior scores, which characterize the degree to which dose is delivered anteriorly. The overall quality of each plan was compared using a virtual dose-escalation study. For US plans, rectal mean dose was inversely correlated with anterior score, but for PBS plans there was no association between rectal mean dose and anterior score. For both US and PBS plans, full bladder and empty bladder mean doses were correlated with anterior scores. For both US and PBS plans, femoral head mean doses were inversely correlated with anterior score. For US plans and a full bladder, 4 beam arrangements that included an anterior beam tied for the highest maximum prescription dose (MPD). For US plans and an empty bladder, the arrangement with 1 anterior and 2 anterior oblique beams achieved the highest MPD in the virtual dose-escalation study. The dose-escalation study did not differentiate beam arrangements for PBS. All arrangements in the dose-escalation study were limited by bladder constraints except for the arrangement with 2 posterior oblique beams. The benefits of anterior proton beams in the setting of prostate-rectum spacers appear to be proton modality dependent and may not extend to PBS. (C) 2013 American Association of Medical Dosimetrists. C1 [Christodouleas, John P.; Tang, Shikui; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha; Both, Stefan] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19081 USA. [Susil, Robert C.; McNutt, Todd R.; Song, Danny Y.; DeWeese, Theodore L.] Johns Hopkins Univ Hosp, Dept Radiat Oncol & Radiat Mol Sci, Baltimore, MD 21287 USA. [Lu, Hsiao-Ming] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Christodouleas, JP (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 3400 Civ Ctr Blvd, Philadelphia, PA 19081 USA. EM christojo@uphs.upenn.edu RI Deville, Curtiland/B-2819-2013 OI Deville, Curtiland/0000-0003-4846-6486 FU NCI NIH HHS [P30 CA006973] NR 20 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 J9 MED DOSIM JI Med. Dosim. PD FAL PY 2013 VL 38 IS 3 BP 315 EP 319 DI 10.1016/j.meddos.2013.03.002 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 199WA UT WOS:000323025000016 PM 23578497 ER PT J AU VanElzakker, MB AF VanElzakker, Michael B. TI Chronic fatigue syndrome from vagus nerve infection: A psychoneuroimmunological hypothesis SO MEDICAL HYPOTHESES LA English DT Article ID TO-BRAIN COMMUNICATION; ACUTE-PHASE RESPONSE; EPSTEIN-BARR-VIRUS; HIV-1 ENVELOPE GLYCOPROTEIN; INDUCED SICKNESS BEHAVIOR; PRIMARY AFFERENT NEURONS; MILD ORTHOSTATIC-STRESS; HERPES-SIMPLEX VIRUS; SUBDIAPHRAGMATIC VAGOTOMY; HUMAN HERPESVIRUS-6 AB Chronic fatigue syndrome (CFS) is an often-debilitating condition of unknown origin. There is a general consensus among CFS researchers that the symptoms seem to reflect an ongoing immune response, perhaps due to viral infection. Thus, most CFS research has focused upon trying to uncover that putative immune system dysfunction or specific pathogenic agent. However, no single causative agent has been found. In this speculative article, I describe a new hypothesis for the etiology of CFS: infection of the vagus nerve. When immune cells of otherwise healthy individuals detect any peripheral infection, they release proinflammatory cytokines. Chemoreceptors of the sensory vagus nerve detect these localized proinflammatory cytokines, and send a signal to the brain to initiate sickness behavior. Sickness behavior is an involuntary response that includes fatigue, fever, myalgia, depression, and other symptoms that overlap with CFS. The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia or paraganglia are themselves infected with any virus or bacteria. Drawing upon relevant findings from the neuropathic pain literature, I explain how pathogen-activated glial cells can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen. The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies. (C) 2013 Elsevier Ltd. All rights reserved. C1 Tufts Univ Psychol, Massachusetts Gen Hosp Psychiat Neurosci, Medford, MA 02155 USA. RP VanElzakker, MB (reprint author), Tufts Univ Psychol, Massachusetts Gen Hosp Psychiat Neurosci, 490 Boston Ave, Medford, MA 02155 USA. EM michael.vanelzakker@gmail.com FU National Defense Science and Engineering Graduate (NDSEG) fellowship; Tufts University Psychology Graduate Program FX Grant support comes from a National Defense Science and Engineering Graduate (NDSEG) fellowship to M.B.V, and the Tufts University Psychology Graduate Program. Funding sources had no role in the content of this manuscript. The author declares no conflicts of interest. NR 140 TC 6 Z9 6 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD SEP PY 2013 VL 81 IS 3 BP 414 EP 423 DI 10.1016/j.mehy.2013.05.034 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 210ZR UT WOS:000323874400013 PM 23790471 ER PT J AU Chen, C Zhang, C Xu, JM Han, Y AF Chen, Chan Zhang, Cheng Xu, Jun-Mei Han, Yong TI LGR5 is a biomarker for stratification of HER-2 positive breast cancer patients and personalized treatment SO MEDICAL HYPOTHESES LA English DT Article ID TRASTUZUMAB RESISTANCE; GASTRIC-CANCER; MESENCHYMAL TRANSITION; WNT/BETA-CATENIN; POOR-PROGNOSIS; RECEPTORS; HERCEPTIN; ASSOCIATION; CONTRIBUTES; EXPRESSION AB VEGFR and HER2 are both important transmembrane proteins associated with several types of cancer. Overexpression of these 2 proteins had long been thought to contribute to cancer progression and poor outcomes, thus, therapies targeting HER-2 and VEGFA signaling pathways have been applied in recent years. Herceptin is a HER-2 targeted antibody that being widely used for the management of HER-2 positive breast cancer, which demonstrate significant benefits in both the metastatic and adjuvant settings. However, acquired resistance develops in most treated patients despite treatment in as early as 10 months. Identification of subpopulations best suited for and most likely to respond to Herceptin is of utmost importance. We analyzed the signaling pathways of HER-2 and found that HER-2 shares a very similar downstream network with VEGFA, while LGR5 lies in the upstream of VEGFA and could promotes its expression through CTNNB1. This discovery suggests that the LGR5 directed VEGFA overexpression may activate downstream signals of HER-2 despite Herceptin treatment. Here, we hypothesized that in LGR5 overexpressing breast cancer cases, activation of VEGFA-VRGFR bypass may account for the resistance to HER-2 directed therapies. Concurrent inhibition of VEGFR might enhance Herceptin sensitivity and moreover reverse the resistant phenotype in HER-2 positive breast cancer. Thus, we proposed alternate regimens to increase the efficacy of Herceptin-based therapy. Nevertheless, wet lab experiments and clinical trials are still required. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Chen, Chan; Xu, Jun-Mei] Cent S Univ, Anesthesiol Res Inst, Xiangya Hosp 2, Dept Anesthesiol, Changsha, Hunan, Peoples R China. [Zhang, Cheng] Peking Univ, Key Lab Carcinogenesis & Translat Res, Dept Biochem & Mol Biol, Minist Educ,Canc Hosp & Inst, Beijing 100871, Peoples R China. [Han, Yong] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Han, Y (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 11th Floor,3 Blakfan Circle, Boston, MA 02115 USA. EM doctorjmxu@gmail.com; Yong@jimmy.harvard.edu FU China Scholarship Council FX This study was funded by China Scholarship Council. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 24 TC 0 Z9 0 U1 1 U2 12 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD SEP PY 2013 VL 81 IS 3 BP 439 EP 442 DI 10.1016/j.mehy.2013.06.004 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 210ZR UT WOS:000323874400018 PM 23830593 ER PT J AU Guddati, AK Kumar, N Segon, A Joy, PS Marak, CP Kumar, G AF Guddati, Achuta K. Kumar, Nilay Segon, Ankur Joy, Parijat S. Marak, Creticus P. Kumar, Gagan TI Identifying oncological emergencies SO MEDICAL ONCOLOGY LA English DT Review DE Oncological emergencies; SVC syndrome; Spinal cord compression; Airway obstruction; Leukostasis ID DISSEMINATED INTRAVASCULAR COAGULATION; INFECTIOUS-DISEASES SOCIETY; CLINICAL-PRACTICE GUIDELINE; CANCER 2010 UPDATE; ANTIMICROBIAL AGENTS; NEUTROPENIC PATIENTS; MANAGEMENT; DIAGNOSIS; AMERICA; INDUCTION AB Prompt identification and treatment of life-threatening oncological conditions is of utmost importance and should always be included in the differential diagnosis. Oncological emergencies can have a myriad of presentations ranging from mechanical obstruction due to tumor growth to metabolic conditions due to abnormal secretions from the tumor. Notably, hematologic and infectious conditions may complicate the presentation of oncological emergencies. Advanced testing and imaging is generally required to recognize these serious presentations of common malignancies. Early diagnosis and treatment of these conditions can significantly affect the patient's clinical outcome. C1 [Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. [Kumar, Nilay; Segon, Ankur; Kumar, Gagan] Froedtert, Sect Hosp Med, Milwaukee, WI USA. [Kumar, Nilay; Segon, Ankur; Kumar, Gagan] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Joy, Parijat S.] Univ Iowa, Univ Iowa Hosp, Dept Internal Med, Iowa, IA USA. [Marak, Creticus P.] Tahlequah City Hosp, Sect Pulm Med, Tahlequah, OK USA. RP Guddati, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, 50 Fruit St, Boston, MA 02115 USA. EM aguddati@partners.org NR 20 TC 3 Z9 3 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD SEP PY 2013 VL 30 IS 3 AR UNSP 669 DI 10.1007/s12032-013-0669-6 PG 10 WC Oncology SC Oncology GA 208FN UT WOS:000323662900017 PM 23873016 ER PT J AU Martin, LP Krasner, C Rutledge, T Ibanes, ML Fernandez-Garcia, EM Kahatt, C Gomez, MS McMeekin, S AF Martin, Lainie P. Krasner, Carolyn Rutledge, Teresa Luque Ibanes, Manuel Fernandez-Garcia, Eva M. Kahatt, Carmen Siguero Gomez, Mariano McMeekin, Scott TI Phase II study of weekly PM00104 (ZALYPSIS (R)) in patients with pretreated advanced/metastatic endometrial or cervical cancer SO MEDICAL ONCOLOGY LA English DT Article DE PM00104; Phase II; Second line; Single-agent; Endometrial cancer; Cervical cancer ID SOLID TUMORS AB This open-label, two-arm, phase II clinical trial evaluated the antitumor activity and safety profile of PM00104 (Zalypsis (R)) administered as a 1-h, weekly, intravenous infusion (days 1, 8 and 15; every 4 weeks) at a dose of 2 mg/m(2) to patients with advanced and/or metastatic endometrial (EC) or cervical cancer (CC) after one previous line of systemic chemotherapy. Twelve patients (median age, 61.5 years) with pretreated EC received a median of 2 treatment cycles (range 1-5) and seven patients (median age, 38 years) with pretreated CC received 2 treatment cycles. None achieved objective tumor response. Median progression-free survival (PFS) was 1.8 months, and median overall survival (OS) was 5.5 months in EC (median follow-up = 20.1 months); median PFS was 1.5 months, and median OS was 5.6 months in CC (median follow-up = 17.1 months). The most common toxicities reported were mild to moderate asthenia, nausea, vomiting and diarrhea. Despite PM00104 showing mostly mild, predictable, manageable and reversible toxicity, protocol criteria for further recruitment were not met in EC, a futility analysis was done and recruitment was stopped; a low patient recruitment rate together with no evidence of activity in CC resulted in early study closure. C1 [Martin, Lainie P.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Krasner, Carolyn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rutledge, Teresa] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Luque Ibanes, Manuel; Fernandez-Garcia, Eva M.; Kahatt, Carmen; Siguero Gomez, Mariano] Pharma Mar SA, Madrid, Spain. [McMeekin, Scott] Univ Oklahoma, OU Canc Inst, Norman, OK 73019 USA. RP Fernandez-Garcia, EM (reprint author), Pharma Mar SA, Madrid, Spain. EM Lainie.Martin@fccc.edu; emfernandez@pharmamar.com RI Luque, Inmaculada/K-9464-2014 OI Luque, Inmaculada/0000-0003-1838-2636 NR 9 TC 6 Z9 6 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD SEP PY 2013 VL 30 IS 3 AR UNSP 627 DI 10.1007/s12032-013-0627-3 PG 4 WC Oncology SC Oncology GA 208FN UT WOS:000323662900056 PM 23771800 ER PT J AU Tse, JY Wu, SL Shinagare, SA Lauwers, GY Yilmaz, O Wu, CL Deshpande, V AF Tse, Julie Y. Wu, Shulin Shinagare, Shweta A. Lauwers, Gregory Y. Yilmaz, Omer Wu, Chin-Lee Deshpande, Vikram TI Peutz-Jeghers syndrome: a critical look at colonic Peutz-Jeghers polyps SO MODERN PATHOLOGY LA English DT Article DE colon; desmin; Peutz-Jeghers polyp; Peutz-Jeghers syndrome ID LKB1; SUPPRESSION; METABOLISM; MANAGEMENT AB Peutz-Jeghers syndrome is an autosomal dominant condition characterized by gastrointestinal hamartomatous polyps. The pathologic identification of a Peutz-Jeghers polyp is integral to the diagnosis of this syndrome that often remains undiagnosed until after these polyps are identified. Histologically, Peutz-Jeghers polyps are characterized by a distinctive arborization of smooth muscle within the lamina propria. Colonic Peutz-Jeghers polyps, however, may mimic mucosal prolapse polyps or virtually any colonic polyp that undergoes prolapse. In this paper, we explore the morphological features of colonic Peutz-Jeghers polyps and the diagnostic challenges associated with these polyps. Colonic polyps from patients with Peutz-Jeghers syndrome were identified (n=34). The control cohort, included mucosal prolapse polyps (n=5), hyperplastic polyps (n=10) and tubular adenomas with prolapse (n=9), ganglioneuromatous polyps (n=2) and juvenile polyps (n=14). Intramucosal smooth muscle fibers were identified in all classes of polyps. Twenty-three of the 34 colonic Peutz-Jeghers polyps were characterized by lobulated clusters of colonic crypts. On immunohistochemistry, desmin-positive smooth muscle fibers were seen surrounding these lobules. This lobular organization of the crypts was not identified in mucosal prolapse polyps and hyperplastic polyps or tubular adenomas with prolapse; only one of the 14 juvenile polyps showed this pattern of reactivity on a desmin stain. Our data suggests that the histologic hallmark of colonic Peutz-Jeghers polyps is the lobular organization of the crypts, and that an arborizing pattern of smooth muscle proliferation is neither sensitive nor a specific marker of colonic Peutz-Jeghers polyps. The presence of desmin-positive smooth muscle fibers surrounding the lobules is a helpful diagnostic feature of colonic Peutz-Jeghers polyps, and facilitates the distinction of these polyps from non-Peutz-Jeghers polyps with prolapse-like changes. C1 [Tse, Julie Y.; Wu, Shulin; Shinagare, Shweta A.; Lauwers, Gregory Y.; Yilmaz, Omer; Wu, Chin-Lee; Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM vikramdirdeshpande@gmail.com FU National Institutes of Health [1P01CA120964] FX This work was supported by grant 1P01CA120964 from the National Institutes of Health to C-L Wu. NR 10 TC 4 Z9 4 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2013 VL 26 IS 9 BP 1235 EP 1240 DI 10.1038/modpathol.2013.44 PG 6 WC Pathology SC Pathology GA 212VO UT WOS:000324011100010 PM 23599156 ER PT J AU Dekel, S Peleg, T Solomon, Z AF Dekel, Sharon Peleg, Tamar Solomon, Zahava TI The Relationship of PTSD to Negative Cognitions: A 17-Year Longitudinal Study SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; WORLD ASSUMPTIONS; PROCESSING THERAPY; ASSAULT SURVIVORS; TRAUMATIC EVENTS; WAR CAPTIVITY; MENTAL-HEALTH; VETERANS; MEMORY; ADULTS AB With the growing interest in the role of cognitions in PTSD, this prospective study examined the course and bi-directional relationship between post-trauma cognitions and symptoms of PTSD. A sample of Israeli combat veterans, including former prisoners of war, was assessed in 1991, and later followed up in 2003 and 2008. PTSD symptoms were measured at three time points. Cognitions concerning the self and the world were measured twice. Applying Autoregressive Cross-Lagged (ARCL) modeling strategy, initial PTSD symptoms predicted subsequent negative cognitions but not vice versa. In addition, repeated measures design revealed that individuals with chronic PTSD symptoms had relatively negative cognitions that further amplified with time. More specifically, increasingly negative cognitions were documented among ex-prisoners of war. The main findings suggest that negative cognitions are fueled by PTSD and that in chronic PTSD there is an amplification of pathogenic outcomes over time. Discussion of the findings is in the context of current cognitive models of PTSD. C1 [Dekel, Sharon] Massachusetts Gen Hosp East, PTSD Res Lab, Charlestown, MA 02129 USA. [Solomon, Zahava] Tel Aviv Univ, Bob Shapell Sch Social Work, IL-69978 Tel Aviv, Israel. [Peleg, Tamar] Ben Gurion Univ Negev, Dept Social Work, IL-84105 Beer Sheva, Israel. RP Dekel, S (reprint author), Massachusetts Gen Hosp East, PTSD Res Lab, 120 2nd Ave, Charlestown, MA 02129 USA. EM dekel.sharon@gmail.com FU Brain and Behavior Research Foundation FX This study was supported by the Young Investigator Grant of the Brain and Behavior Research Foundation sponsored by Dr. Dylan Tauber, which was awarded to Sharon Dekel. NR 56 TC 9 Z9 9 U1 0 U2 16 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2013 VL 76 IS 3 BP 241 EP 255 PG 15 WC Psychiatry SC Psychiatry GA 210TD UT WOS:000323856600005 PM 23965263 ER PT J AU Stein, MB Jacobo, MC AF Stein, Michelle B. Jacobo, Michelle C. TI Brief Inpatient Psychotherapeutic Technique SO PSYCHOTHERAPY LA English DT Article DE inpatient psychotherapy; clinical training; therapeutic technique ID BORDERLINE PERSONALITY-DISORDER; DIALECTICAL BEHAVIOR-THERAPY; INTERPERSONAL DISTRESS; EMOTION; ALLIANCE; SCALE AB Trainees rotate onto the medical psychiatric inpatient unit at Massachusetts General Hospital every 6 weeks to learn how to conduct brief inpatient psychotherapy from two staff psychologists and one staff psychiatrist. This article focuses on four key therapeutic principles/techniques used when teaching these trainees about brief inpatient psychotherapy. These include support, affective experience and expression, chain analysis, and identification of relational styles/maladaptive relational patterns. We also briefly discuss our approach to training. Theoretical rationale, numerous clinical examples, and empirical support (of inpatient psychotherapy) are provided. C1 [Stein, Michelle B.; Jacobo, Michelle C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stein, Michelle B.; Jacobo, Michelle C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stein, MB (reprint author), Massachusetts Gen Hosp, Psychol Evaluat & Res Lab PEaRL, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mstein3@partners.org NR 32 TC 0 Z9 0 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD SEP PY 2013 VL 50 IS 3 SI SI BP 464 EP 468 DI 10.1037/a0032549 PG 5 WC Psychology, Clinical SC Psychology GA 210RS UT WOS:000323852800041 PM 24000872 ER PT J AU Wamsley, EJ Shinn, AK Tucker, MA Ono, KE McKinley, SK Ely, AV Goff, DC Stickgold, R Manoach, DS AF Wamsley, Erin J. Shinn, Ann K. Tucker, Matthew A. Ono, Kim E. McKinley, Sophia K. Ely, Alice V. Goff, Donald C. Stickgold, Robert Manoach, Dara S. TI The Effects of Eszopiclone on Sleep Spindles and Memory Consolidation in Schizophrenia: A Randomized Placebo-Controlled Trial SO SLEEP LA English DT Article DE Schizophrenia; procedural learning; motor skill; sleep spindles; memory consolidation; automation ID COGNITION; SLOW; BENZODIAZEPINE; PERFORMANCE; OLANZAPINE; RECEPTORS; THALAMUS; INSOMNIA; EFFICACY; DEFICITS AB Study Objectives: In schizophrenia there is a dramatic reduction of sleep spindles that predicts deficient sleep-dependent memory consolidation. Eszopiclone (Lunesta), a non-benzodiazepine hypnotic, acts on.-aminobutyric acid (GABA) neurons in the thalamic reticular nucleus where spindles are generated. We investigated whether eszopiclone could increase spindles and thereby improve memory consolidation in schizophrenia. Design: In a double-blind design, patients were randomly assigned to receive either placebo or 3 mg of eszopiclone. Patients completed Baseline and Treatment visits, each consisting of two consecutive nights of polysomnography. On the second night of each visit, patients were trained on the motor sequence task (MST) at bedtime and tested the following morning. Setting: Academic research center. Participants: Twenty-one chronic, medicated schizophrenia outpatients. Measurements and Results: We compared the effects of two nights of eszopiclone vs. placebo on stage 2 sleep spindles and overnight changes in MST performance. Eszopiclone increased the number and density of spindles over baseline levels significantly more than placebo, but did not significantly enhance overnight MST improvement. In the combined eszopiclone and placebo groups, spindle number and density predicted overnight MST improvement. Conclusion: Eszopiclone significantly increased sleep spindles, which correlated with overnight motor sequence task improvement. These findings provide partial support for the hypothesis that the spindle deficit in schizophrenia impairs sleep-dependent memory consolidation and may be ameliorated by eszopiclone. Larger samples may be needed to detect a significant effect on memory. Given the general role of sleep spindles in cognition, they offer a promising novel potential target for treating cognitive deficits in schizophrenia. C1 [Wamsley, Erin J.; Tucker, Matthew A.; McKinley, Sophia K.; Ely, Alice V.; Stickgold, Robert] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Wamsley, Erin J.; Tucker, Matthew A.; McKinley, Sophia K.; Ely, Alice V.; Stickgold, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Shinn, Ann K.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. [Ono, Kim E.; Goff, Donald C.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp Charlestown Navy Yard, 149 13th St,Room 1-111, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu FU Sunovion Pharmaceuticals, Inc. [30675]; National Institutes of Health [R01-MH48832, T32-HL07901]; National Center for Research Resources [UL1-RR025758, M01-RR-01066]; Harvard Clinical and Translational Science Center; PamLab; Novartis; GlaxoSmithKline; Pfizer, Inc.; Merck Co. FX This work was funded by research Grant #30675 to Dr. Manoach from Sunovion Pharmaceuticals, Inc. (formerly Sepracor, Inc.) which markets eszopiclone; the National Institutes of Health R01-MH48832 and T32-HL07901; and the National Center for Research Resources UL1-RR025758 and M01-RR-01066, Harvard Clinical and Translational Science Center.; Dr. Goff has participated in trials funded by PamLab, Novartis, GlaxoSmithKline, and Pfizer, Inc. Dr. Shinn's salary is paid in part through grants from Merck & Co., and Pfizer, Inc. The other authors have indicated no financial conflicts of interest. NR 52 TC 24 Z9 24 U1 3 U2 10 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD SEP 1 PY 2013 VL 36 IS 9 BP 1369 EP 1376 DI 10.5665/sleep.2968 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 211DX UT WOS:000323886100016 PM 23997371 ER PT J AU Palioura, S Jakobiec, FA Zakka, FR Iwamoto, M AF Palioura, Sotiria Jakobiec, Frederick A. Zakka, Fouad R. Iwamoto, Mami TI Pleomorphic adenoma (formerly chondroid syringoma) of the eyelid margin with a pseudocystic appearance SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE pleomorphic adenoma; chondroid syringoma; benign mixed tumor; eyelid skin; apocrine gland; eccrine gland; cytokeratin 7; gross cystic fluid disease protein-15; alpha-smooth muscle actin ID BENIGN MIXED TUMOR; LACRIMAL GLAND TISSUE; PALPEBRAL LOBE; SWEAT GLAND; CYSTIC CARCINOMA; CLINICAL PRESENTATION; SURGICAL-MANAGEMENT; ORIGIN; SKIN; PAPILLIFERUM AB Among the adenomas and adenocarcinomas spawned by the adnexal glands of the eyelids, pleomorphic adenoma (also referred to as benign mixed tumor or chondroid syringoma in dermatopathology) is among the rarest. Pleomorphic adenomas (PAs) can arise from sweat glands in the dermis of the eyelid skin and must be distinguished from those of the accessory lacrimal glands of Krause and Wolfring. We describe an eyelid margin skin PA that appeared clinically to be a cyst and was not associated with an accessory lacrimal gland. Histopathologically, the lesion was circumscribed but nonencapsulated and composed of branching ductular structures with a double layer of epithelial cells set in a myxoid and sclerotic stoma that did not contain cartilage. The outer ductular (myoepithelial) cells delaminated to populate the stroma. Histochemistry disclosed abundant extracellular mucopolysaccharides that conferred the "cystic" character clinically. The inner ductular cells were uniformly positive for cytokeratin 7 and focally for gross cystic fluid disease protein-15, an apocrine marker. The inner and outer ductular cells were negative for alpha-smooth muscle actin. These pathologic findings support an apocrine (gland of Moll) origin for this tumor, which is consistent with the fact that there are no eccrine glands at the eyelid margin. (c) 2013 Elsevier Inc. All rights reserved. C1 [Palioura, Sotiria; Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA USA. [Palioura, Sotiria; Jakobiec, Frederick A.; Zakka, Fouad R.; Iwamoto, Mami] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Iwamoto, Mami] Ophthalm Consultants Boston, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 321, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 69 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD SEP-OCT PY 2013 VL 58 IS 5 BP 486 EP 491 DI 10.1016/j.survophthal.2012.10.003 PG 6 WC Ophthalmology SC Ophthalmology GA 210VO UT WOS:000323863000006 PM 23294914 ER PT J AU Arbel-Ornath, M Hudry, E Eikermann-Haerter, K Hou, S Gregory, JL Zhao, LZ Betensky, RA Frosch, MP Greenberg, SM Bacskai, BJ AF Arbel-Ornath, Michal Hudry, Eloise Eikermann-Haerter, Katharina Hou, Steven Gregory, Julia L. Zhao, Lingzhi Betensky, Rebecca A. Frosch, Matthew P. Greenberg, Steven M. Bacskai, Brian J. TI Interstitial fluid drainage is impaired in ischemic stroke and Alzheimer's disease mouse models SO ACTA NEUROPATHOLOGICA LA English DT Article DE Alzheimer's disease; Amyloid beta; Cerebral amyloid angiopathy; Interstitial fluids; Ischemic stroke; Perivascular space ID CEREBRAL AMYLOID ANGIOPATHY; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; SUBARACHNOID SPACES; CEREBROSPINAL-FLUID; APOLIPOPROTEIN-E; BETA-PEPTIDE; RAT-BRAIN; PATHWAYS; PATHOLOGY AB The interstitial fluid (ISF) drainage pathway has been hypothesized to underlie the clearance of solutes and metabolites from the brain. Previous work has implicated the perivascular spaces along arteries as the likely route for ISF clearance; however, it has never been demonstrated directly. The accumulation of amyloid beta (A beta) peptides in brain parenchyma is one of the pathological hallmarks of Alzheimer disease (AD), and it is likely related to an imbalance between production and clearance of the peptide. A beta drainage along perivascular spaces has been postulated to be one of the mechanisms that mediate the peptide clearance from the brain. We therefore devised a novel method to visualize solute clearance in real time in the living mouse brain using laser guided bolus dye injections and multiphoton imaging. This methodology allows high spatial and temporal resolution and revealed the kinetics of ISF clearance. We found that the ISF drains along perivascular spaces of arteries and capillaries but not veins, and its clearance exhibits a bi-exponential profile. ISF drainage requires a functional vasculature, as solute clearance decreased when perfusion was impaired. In addition, reduced solute clearance was observed in transgenic mice with significant vascular amyloid deposition; we suggest the existence of a feed-forward mechanism, by which amyloid deposition promotes further amyloid deposition. This important finding provides a mechanistic link between cerebrovascular disease and Alzheimer disease and suggests that facilitation of A beta clearance along the perivascular pathway should be considered as a new target for therapeutic approaches to Alzheimer disease and cerebral amyloid angiopathy. C1 [Arbel-Ornath, Michal; Hudry, Eloise; Hou, Steven; Gregory, Julia L.; Zhao, Lingzhi; Frosch, Matthew P.; Greenberg, Steven M.; Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, Charlestown, MA 02129 USA. [Arbel-Ornath, Michal; Hudry, Eloise; Eikermann-Haerter, Katharina; Hou, Steven; Gregory, Julia L.; Zhao, Lingzhi; Frosch, Matthew P.; Greenberg, Steven M.; Bacskai, Brian J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Eikermann-Haerter, Katharina] Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, 114,16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org FU National Institute of Health [EB000768] FX We wish to express our gratitude to Dr. K. V. Kuchibhotla, Dr. A. Serrano-Pozo and Dr. T. L. Spires-Jones for fruitful discussions and careful reading and editing of the manuscript. This work was supported by the National Institute of Health (Grant No. EB000768). NR 50 TC 47 Z9 50 U1 2 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD SEP PY 2013 VL 126 IS 3 BP 353 EP 364 DI 10.1007/s00401-013-1145-2 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 206RU UT WOS:000323540700003 PM 23818064 ER PT J AU Oh, B Kimble, B Costa, DSJ Davis, E McLean, A Orme, K Beith, J AF Oh, B. Kimble, B. Costa, D. S. J. Davis, E. McLean, A. Orme, K. Beith, J. TI Acupuncture for treatment of arthralgia secondary to aromatase inhibitor therapy in women with early breast cancer: pilot study SO ACUPUNCTURE IN MEDICINE LA English DT Article DE COMPLEMENTARY MEDICINE; PAIN MANAGEMENT; PAIN RESEARCH; THERAPEUTICS ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; ALTERNATIVE MEDICINE; PLACEBO ACUPUNCTURE; COMPLEMENTARY; OSTEOARTHRITIS; MULTICENTER; MANAGEMENT; SYMPTOMS; EFFICACY AB Background Aromatase inhibitors (AIs) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer. A substantial proportion of women taking AIs experience joint pain and stiffness. Studies have suggested that acupuncture may be effective in treating joint pain. Objective A pilot study was conducted to evaluate the feasibility, safety and efficacy of using acupuncture to treat AI-induced arthralgia. Methods A total of 32 patients were randomised to receive either sham or real electroacupuncture (EA) twice weekly for 6weeks. Outcomes of joint pain, stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), overall pain severity and interference with the BPI-SF and quality of life (QOL) with the Functional Assessment of Cancer Therapy-General (FACT-G) instrument. Hand strength was assessed by a grip test, and a serum marker of inflammation (C reactive protein (CRP)) was also measured. All assessments were performed at baseline, 6weeks and 12weeks, except for blood samples at baseline and 6weeks only. Results No serious adverse events were reported during or after acupuncture treatments. There were no significant differences in outcome measures. However, positive trends were observed in stiffness and physical function at week 12 in favour of real EA. Conclusions Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI. A larger study with adequately powered to confirm these results and detect clinically relevant effects is needed. C1 [Oh, B.; McLean, A.; Beith, J.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Oh, B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kimble, B.; Orme, K.; Beith, J.] Royal Prince Alfred Hosp, Sydney Canc Ctr, Sydney, NSW, Australia. [Costa, D. S. J.; Davis, E.] Univ Sydney, Psychooncol Cooperat Res Grp PoCoG, Sydney, NSW 2006, Australia. RP Davis, E (reprint author), Univ Sydney, Psychooncol Cooperat Res Grp PoCoG, Sydney, NSW 2006, Australia. EM esther.davis@sydney.edu.au RI cmu, library/L-1810-2013; OI Beith, Jane/0000-0002-4946-2789 FU Cancer Institute NSW Innovative Grant; Sydney South West Area Health Service, NSW Department of Health FX This study was awarded the Cancer Institute NSW Innovative Grant in 2008 and supported by the Sydney South West Area Health Service, NSW Department of Health. NR 41 TC 13 Z9 14 U1 1 U2 27 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-5284 J9 ACUPUNCT MED JI Acupunct. Med. PD SEP PY 2013 VL 31 IS 3 BP 264 EP 271 DI 10.1136/acupmed-2012-010309 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 208YU UT WOS:000323719800002 PM 23722951 ER PT J AU Mimiaga, MJ Biello, KB Sivasubramanian, M Mayer, KH Anand, VR Safren, SA AF Mimiaga, Matthew J. Biello, Katie Brooks Sivasubramanian, Murugesan Mayer, Kenneth H. Anand, Vivek Raj Safren, Steven A. TI Psychosocial risk factors for HIV sexual risk among Indian men who have sex with men SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE men who have sex with men (MSM); Mumbai; India; mental health; depression; minority stress; HIV ID CHENNAI; DEPRESSION; SYMPTOMS; BEHAVIOR; HEALTH AB Indian men who have sex with men (MSM) are at increased risk for HIV compared to the general Indian population. Psychosocial factors may be uniquely associated with HIV risk among Indian MSM and may moderate the beneficial impact of standard HIV prevention approaches. Psychiatric diagnostic interviews and psychosocial and sexual risk assessments were conducted among 150 MSM in Mumbai, India. Logistic regression was employed to examine the association of psychiatric disorders and psychosocial problems to recent sexual risk behavior. Twenty-five percent of participants reported engaging in unprotected anal sex (UAS) during their last sexual contact with a man. Men who were married to a woman were more likely to have engaged in UAS during their last sexual contact with a man (35% vs. 17%, p=0.018). In multivariable models, significant predictors of engaging in UAS were current major depression (adjusted odds ratio [AOR]=2.61; 95% confidence interval [CI] 1.07, 6.39) and number of stressful life events (AOR=0.91; 95% CI 0.83, 0.99). Alcohol dependence, anxiety, and self-esteem were not associated with engaging in UAS. Indian MSM with depression are at higher odds of engaging in UAS compared to MSM without depression. HIV prevention programs for Indian MSM may benefit from incorporating treatment or triage for mental health problems. C1 [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Biello, Katie Brooks] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Biello, Katie Brooks; Mayer, Kenneth H.; Safren, Steven A.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Sivasubramanian, Murugesan; Anand, Vivek Raj] Humsafar Trust, Bombay, Maharashtra, India. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Infect Dis, Boston, MA 02215 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM mmimiaga@hsph.harvard.edu FU NIDA NIH HHS [R21 DA033720, 1R21DA0.33.720-01]; NIMH NIH HHS [K24 MH094214, K24MH0.94.214] NR 16 TC 13 Z9 14 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD SEP 1 PY 2013 VL 25 IS 9 BP 1109 EP 1113 DI 10.1080/09540121.2012.749340 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 207VQ UT WOS:000323633200006 PM 23339580 ER PT J AU Huynh, AK Kinsler, JJ Cunningham, WE Sayles, JN AF Huynh, Alexis K. Kinsler, Janni J. Cunningham, William E. Sayles, Jennifer N. TI The role of mental health in mediating the relationship between social support and optimal ART adherence SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; AIDS; ART adherence; social support; mental health; mediation analyses ID ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; HIV-POSITIVE MEN; MEDICATION ADHERENCE; DEPRESSION; WOMEN; INTERVENTION; ADULTS AB Optimal adherence to antiretroviral therapy (ART) is essential for reducing mortality and morbidity in persons living with HIV/AIDS (PLWHA), as well as for reducing the risk of further HIV transmission. While studies have identified psychosocial factors such as lack of social support and poor mental health status as important barriers to optimal ART adherence, few studies have explored the potential of a mediation effect of psychosocial factors on the relationship between social support and optimal ART adherence. This paper assessed whether mental health status mediated the relationship between social support and optimal ART adherence among a cross-sectional sample of 202 persons living with HIV who were recruited from HIV clinical care sites and community-based organizations in Los Angeles County (LAC). Participants completed a survey that included social support items from the Medical Outcome Study: Social Support Survey (MOS-SSS) Instrument, mental health measures from the Medical Outcomes Study Short Form (SF-12), and ART adherence based on self-report. Among those currently taking ART, 61.7% reported having optimal adherence. Social support was significantly associated with a high score on the mental health status scale (AOR =2.90; 95% CI=1.14-5.78) and optimal ART adherence (AOR=1.81; 95% CI=1.81; 95% CI=1.18-2.79). When mental health status was introduced into the model, the association between social support and optimal ART adherence was no longer significant. Our findings suggest the HIV interventions targeting social support to improve ART adherence will likely be most successful if the support bolsters the mental health of the participants. Clearly, better understanding the relationships among social support, mental health, and ART adherence will be critical for development and implementation of future ART adherence interventions. C1 [Huynh, Alexis K.; Cunningham, William E.; Sayles, Jennifer N.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Huynh, Alexis K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kinsler, Janni J.] Univ Calif Los Angeles, Dept Community Hlth Sci, Los Angeles, CA USA. [Cunningham, William E.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Kinsler, JJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. EM jkinsler@ucla.edu FU NIA NIH HHS [P30 AG021684]; NIMH NIH HHS [K23 MH083535]; NIMHD NIH HHS [P20 MD000182] NR 17 TC 8 Z9 8 U1 0 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD SEP 1 PY 2013 VL 25 IS 9 BP 1179 EP 1184 DI 10.1080/09540121.2012.752787 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 207VQ UT WOS:000323633200016 PM 23320407 ER PT J AU Jonassaint, CR Haywood, C Korthuis, PT Cooper, LA Saha, S Sharp, V Cohn, J Moore, RD Beach, MC AF Jonassaint, Charles R. Haywood, Carlton, Jr. Korthuis, Philip Todd Cooper, Lisa A. Saha, Somnath Sharp, Victoria Cohn, Jonathon Moore, Richard D. Beach, Mary Catherine TI The impact of depressive symptoms on patient-provider communication in HIV care SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE depression; communication; quality of health care; patient satisfaction; HIV ID MEDICAL-CARE; PHYSICIAN; ADHERENCE; SATISFACTION; HEALTH; INDIVIDUALS; PREDICTORS; INFECTION; VETERANS; OUTCOMES AB Persons with HIV who develop depression have worse medical adherence and outcomes. Poor patient-provider communication may play a role in these outcomes. This cross-sectional study evaluated the influence of patient depression on the quality of patient-provider communication. Patient-provider visits (n=406) at four HIV care sites were audio-recorded and coded with the Roter Interaction Analysis System (RIAS). Negative binomial and linear regressions using generalized estimating equations tested the association of depressive symptoms, as measured by the Center for Epidemiology Studies Depression scale (CES-D), with RIAS measures and postvisit patient-rated quality of care and provider-reported regard for his or her patient. The patients, averaged 45 years of age (range =20-77), were predominately male (n=286, 68.5%), of black race (n=250, 60%), and on antiretroviral medications (n=334, 80%). Women had greater mean CES-D depression scores (12.0) than men (10.6; p=0.03). There were no age, race, or education differences in depression scores. Visits with patients reporting severe depressive symptoms compared to those reporting none/mild depressive symptoms were longer and speech speed was slower. Patients with severe depressive symptoms did more emotional rapport building but less social rapport building, and their providers did more data gathering/counseling (ps<0.05). In postvisit questionnaires, providers reported lower levels of positive regard for, and rated more negatively patients reporting more depressive symptoms (p<0.01). In turn, patients reporting more depressive symptoms felt less respected and were less likely to report that their provider knows them as a person than none/mild depressive symptoms patients (ps<0.05). Greater psychosocial needs of patients presenting with depressive symptoms and limited time/resources to address these needs may partially contribute to providers' negative attitudes regarding their patients with depressive symptoms. These negative attitudes may ultimately serve to adversely impact patient-provider communication and quality of HIV care. C1 [Jonassaint, Charles R.; Cooper, Lisa A.; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Div Gen Internal Med, Baltimore, MD 21218 USA. [Haywood, Carlton, Jr.] Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD USA. [Haywood, Carlton, Jr.; Cooper, Lisa A.; Beach, Mary Catherine] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Korthuis, Philip Todd; Saha, Somnath] Oregon Hlth & Sci Univ, Dept Med, Gen Internal Med Sect, Portland VA Med Ctr, Portland, OR 97201 USA. [Sharp, Victoria] St Lukes Roosevelt Hosp, Dept Med, New York, NY 10025 USA. [Cohn, Jonathon] Wayne State Univ, Sch Med, Detroit, MI USA. RP Jonassaint, CR (reprint author), Johns Hopkins Univ, Div Gen Internal Med, Baltimore, MD 21218 USA. EM charles.jonassaint@jhmi.edu RI Jonassaint, Charles/I-2772-2014; OI Jonassaint, Charles/0000-0002-5662-5806; Haywood Jr., Carlton/0000-0002-3574-7871 FU NHLBI NIH HHS [K24 HL083113]; NIAAA NIH HHS [R21 AA015032, R01 AA016893]; NIAID NIH HHS [P30 AI094189, U01 AI069918]; NIDA NIH HHS [R01 DA011602]; PHS HHS [AHRQ 290-01-0012] NR 32 TC 1 Z9 1 U1 4 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD SEP 1 PY 2013 VL 25 IS 9 BP 1185 EP 1192 DI 10.1080/09540121.2012.752788 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 207VQ UT WOS:000323633200017 PM 23320529 ER PT J AU Magidson, JF Seitz-Brown, CJ Listhaus, A Lindberg, B Anderson, KE Daughters, SB AF Magidson, Jessica F. Seitz-Brown, C. J. Listhaus, Alyson Lindberg, Briana Anderson, Katelyn E. Daughters, Stacey B. TI Distress Tolerance and Use of Antiretroviral Therapy Among HIV-Infected Individuals in Substance Abuse Treatment SO AIDS PATIENT CARE AND STDS LA English DT Article ID MEDICATION ADHERENCE; DISCOMFORT INTOLERANCE; HAART; ADULTS; CARE AB Despite recent clinical guidelines recommending early initiation and widespread use of antiretroviral therapy (ART), many HIV-infected individuals are not receiving ARTin particular low-income, minority substance users. Few studies have examined psychological, as opposed to structural, factors related to not receiving ART in this population. Perceived capacity to tolerate physical and psychological distress, known as distress tolerance (DT), may be a particularly relevant yet understudied factor. The current study tested the relationship between self-reported physical and psychological DT and ART receipt among predominantly low-income, minority HIV-infected substance users (n=77). Psychiatric disorders, biological indicators of health status, ART use, structural barriers to health care, and self-reported physical and psychological DT were assessed. 61% of participants were receiving ART. The only factors that distinguished individuals not on ART were greater avoidance of physical discomfort, higher psychological DT, and higher CD4 count. Both DT measures remained associated with ART use after controlling for CD4 count and were associated with almost a two-fold decrease in likelihood of ART receipt. Current findings suggest higher perceived capacity to tolerate psychological distress and greater avoidance of physical discomfort are important factors associated with lower ART use among substance users and may be important intervention targets. C1 [Magidson, Jessica F.; Seitz-Brown, C. J.; Listhaus, Alyson; Lindberg, Briana; Anderson, Katelyn E.; Daughters, Stacey B.] Univ Maryland, Dept Behav & Community Hlth, College Pk, MD 20742 USA. [Magidson, Jessica F.; Seitz-Brown, C. J.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Magidson, Jessica F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Daughters, Stacey B.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. RP Magidson, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jmagidson@partners.org FU National Institute of Drug Abuse [R01DA022974, R36DA034513] FX This work was supported by National Institute of Drug Abuse Grants R01DA022974 (PI: Daughters) and R36DA034513 (PI: Magidson). NR 26 TC 3 Z9 3 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP 1 PY 2013 VL 27 IS 9 BP 518 EP 523 DI 10.1089/apc.2013.0120 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 208TR UT WOS:000323703200005 PM 23991690 ER PT J AU Froehlich, JC Hausauer, BJ Federoff, DL Fischer, SM Rasmussen, DD AF Froehlich, Janice C. Hausauer, Brett J. Federoff, David L. Fischer, Stephen M. Rasmussen, Dennis D. TI Prazosin Reduces Alcohol Drinking Throughout Prolonged Treatment and Blocks the Initiation of Drinking in Rats Selectively Bred for High Alcohol Intake SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Prazosin; Alcohol; Alcohol-Preferring (P) Rats; Noradrenergic System; Alcohol Relapse; Alcoholism Pharmacotherapies ID ALPHA(1)-ADRENERGIC RECEPTOR ANTAGONIST; PREFERRING P RATS; ANXIETY DISORDERS; BLOOD-PRESSURE; ETHANOL; STRESS; DEPENDENCE; NEOPHOBIA; BRAIN; RENIN AB Background This study examined whether prazosin reduces alcohol drinking over the course of prolonged treatment and whether it blocks the initiation of alcohol drinking in rats with a genetic predisposition toward high alcohol drinking, that is alcohol-preferring (P) rats. Methods In study one, alcohol-experienced P rats that had been drinking alcohol for 2 h/d for several months were treated daily with prazosin (0, 0.5, 1.0, or 2.0mg/kg body weight [BW]) for 7weeks. In study two, alcohol-naive P rats were treated daily with prazosin (0, 1.0, or 2.0mg/kg BW) for 2weeks prior to, or concomitantly with, the initiation of alcohol access and throughout 3weeks of alcohol availability. Prazosin treatment and alcohol access were then discontinued for 2weeks followed by reinstatement of alcohol access without prazosin treatment for 4weeks, followed by resumption of daily prazosin treatment (2.0mg/kg BW) for 3weeks. Results Prazosin reduced alcohol drinking throughout 7weeks of treatment in P rats accustomed to drinking alcohol. Following termination of prazosin treatment, alcohol drinking slowly returned to pretreatment baseline. Reduced alcohol intake was accompanied by increased water intake. In alcohol-naive P rats, prazosin administration prior to the first opportunity to drink alcohol and throughout 3weeks of alcohol access retarded acquisition of alcohol drinking and reduced the amount of alcohol consumed. When prazosin was administered concomitantly with the first opportunity to drink alcohol, it abolished acquisition of alcohol drinking. Discontinuation of prazosin treatment allowed expression of a genetic predisposition toward high alcohol drinking to gradually emerge. Prazosin retained the ability to reduce alcohol intake with repeated treatments. Conclusions Prazosin decreased alcohol drinking during prolonged treatment and may be useful for treating alcoholism and alcohol-use disorders. Prazosin may also be useful for deterring the initiation of drinking in individuals with a family history of alcoholism. C1 [Froehlich, Janice C.; Hausauer, Brett J.; Federoff, David L.; Fischer, Stephen M.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Froehlich, JC (reprint author), Indiana Univ Sch Med, 975 West Walnut St IB 448, Indianapolis, IN 46202 USA. EM jcfroehl@iupui.edu FU NIH [AA018604, AA07611, AA13881] FX We thank Dr. Ting-Kai Li and the Indiana Alcohol Research Center for supplying the selectively bred rats used in this study. This work was supported by NIH grants AA018604 (JCF and DDR), AA07611 (JCF), and AA13881 (DDR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Alcohol Abuse and Alcoholism or the National Institutes of Health. NR 56 TC 16 Z9 16 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2013 VL 37 IS 9 BP 1552 EP 1560 DI 10.1111/acer.12116 PG 9 WC Substance Abuse SC Substance Abuse GA 208KE UT WOS:000323676600014 PM 23731093 ER PT J AU Saliminejad, M Bemanian, S Ho, A Spiegel, B Laine, L AF Saliminejad, M. Bemanian, S. Ho, A. Spiegel, B. Laine, L. TI The yield and cost of colonoscopy in patients with metastatic cancer of unknown primary SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PRIMARY TUMORS; PRIMARY SITE; CARCINOMA; EPIDEMIOLOGY; PROFILE AB Background Although gastroenterologists are asked to perform colonoscopy in patients with metastatic cancer of unknown primary (MCUP), studies evaluating this practice are lacking. Aim To determine the yield and cost of colonoscopy in patients referred for colonoscopy with an indication of MCUP. Methods We prospectively and retrospectively assessed colonoscopies performed from 2000 to 2011 at a county, a university, and a Veterans Administration medical centre to identify patients referred for colonoscopy for the indication of MCUP. Exclusion criteria included overt or occult bleeding, iron-deficiency anaemia, familial-colon-cancer syndrome, prior colon cancer, imaging suggesting colorectal lesion, and palpable rectal mass. Outcomes were the number of primary colon cancers and costs based on 2012 Medicare reimbursements. Results Two (1%) of the 160 patients meeting enrollment criteria had a primary colon cancer identified, and both died within 1month after diagnosis without receiving therapy targeted at colon cancer. One patient without colon cancer had a perforation because of colonoscopy, which required surgery and colostomy. The cost of a strategy of routinely performing colonoscopy in patients referred with MCUP was $84736 per colon primary identified. Conclusions Primary colon cancer was rarely identified at colonoscopy in patients with MCUP and no standard indications for diagnostic colonoscopy. Furthermore, the cost to diagnose one additional colon primary was very high. Those with colon cancer had advanced disease and were unable to benefit from targeted therapy. Routine colonoscopy for MCUP cannot be recommended at present. C1 [Saliminejad, M.; Bemanian, S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Ho, A.; Spiegel, B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ho, A.; Spiegel, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Laine, L.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Laine, L.] VA Connecticut Healthcare Syst, West Haven, CT USA. RP Laine, L (reprint author), Yale Univ, Sect Digest Dis, Sch Med, POB 208019, New Haven, CT 06520 USA. EM loren.laine@yale.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP PY 2013 VL 38 IS 6 BP 628 EP 633 DI 10.1111/apt.12429 PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 204OC UT WOS:000323375800008 PM 23869398 ER PT J AU Sabodash, V Mendez, MF Fong, S Hsiao, JJ AF Sabodash, Valeriy Mendez, Mario F. Fong, Sylvia Hsiao, Julia J. TI Suicidal Behavior in Dementia: A Special Risk in Semantic Dementia SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE dementia; semantic dementia; Alzheimer's disease; suicide; suicidal; depression; primary progressive aphasia ID ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; DEGENERATION; DYSFUNCTION; CONSENSUS; IDEATION; FEATURES; PEOPLE; MILD; LIFE AB Background: Some studies report a low suicide risk in general dementia and in Alzheimer's disease (AD). Objective: To evaluate suicidal behavior among patients with semantic dementia (SD), a disorder that impairs semantic knowledge. Methods: We reviewed the presence of active suicidal behavior and related factors among 25 patients with SD compared to 111 age-matched patients with early-onset AD. Results: In all, 5 (20%) patients with SD had suicidal behavior (2 successfully killed themselves) compared to 1 (0.9%) with AD (P < .001). There was significantly more depression and greater premorbid history of suicidal behavior among the patients with SD compared to those with AD. Among the patients with SD, those with suicidal behavior, compared to those without, had more depression and greater insight into their deficits. Conclusions: Patients with SD are at special risk of committing suicide, particularly if they have depression and preserved insight. Possible mechanisms include an impaired sense of semantic competence with increased impulsivity. C1 [Sabodash, Valeriy; Mendez, Mario F.; Hsiao, Julia J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Sabodash, Valeriy; Mendez, Mario F.; Fong, Sylvia; Hsiao, Julia J.] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, Los Angeles, CA 90073 USA. [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Sabodash, V (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU National Institute on Aging [R01 AG034499] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: National Institute on Aging R01 AG034499 (MFM). NR 38 TC 7 Z9 8 U1 3 U2 20 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD SEP PY 2013 VL 28 IS 6 BP 592 EP 599 DI 10.1177/1533317513494447 PG 8 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA 207YS UT WOS:000323641500007 PM 23821774 ER PT J AU Mauskopf, J Chirila, C Graham, J Gersten, ID Leather, H Maziarz, RT Baden, LR Bolanos-Meade, J Brown, JMY Walsh, TJ Horowitz, MH Kurtzberg, J Marr, KA Wingard, JR AF Mauskopf, Josephine Chirila, Costel Graham, Jon Gersten, Iris D. Leather, Helen Maziarz, Richard T. Baden, Lindsey R. Bolanos-Meade, Javier Brown, Janice M. Y. Walsh, Thomas J. Horowitz, Mary H. Kurtzberg, Joanne Marr, Kieren A. Wingard, John R. TI Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID VERSUS-HOST-DISEASE; ANTIFUNGAL PROPHYLAXIS; NEUTROPENIC PATIENTS; HIGH-RISK; POSACONAZOLE; ITRACONAZOLE; MICAFUNGIN; RECIPIENTS; TRIAL AB Purpose. The cost-effectiveness of voriconazole versus fluconazole prophylaxis against fungal infections in hematopoietic cell transplant (HCT) recipients is investigated. Methods. A decision-analytic model was developed to estimate the drug costs associated with planned or supplemental prophylaxis and empirical therapy and the costs of treating suspected or documented invasive fungal infections (IFIs) in HCT recipients. Published clinical trial data on 599 patients who received 100-180 days of prophylactic therapy with voriconazole or fluconazole were used to model specified IFI-prevention and mortality outcomes; 6-month, 12-month, and lifetime incremental cost-effectiveness ratios (ICERs) were estimated, with a bootstrap analysis performed to reflect the uncertainty of the clinical trial data. Results. Estimated mean total prophylaxis and IFI-related costs associated with voriconazole versus fluconazole prophylaxis over 12 months were higher in the entire study population and among patients receiving HCT for diagnoses other than acute myeloid leukemia (AML) but were not significantly different for patients with AML. The cost per IFI avoided ($66,919) and the cost per life-year gained ($5,453) were lower among patients with AML who received voriconazole relative to the full study population. ICERs were more favorable for voriconazole over a 6-month time frame and when modeling was conducted using generic price data. Assuming a threshold value of $50,000 for one year of life gained, the calculated probability of voriconazole being cost-effective was 33% for the full study population and 85% for the AML subgroup. Conclusion. The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML. C1 [Mauskopf, Josephine] RTI Hlth Solut, Hlth Econ, Res Triangle Pk, NC USA. [Chirila, Costel; Graham, Jon] RTI Hlth Solut, Res Triangle Pk, NC USA. [Gersten, Iris D.] EMMES Corp, BMT, Rockville, MD USA. [Gersten, Iris D.] EMMES Corp, CTN, Rockville, MD USA. [Gersten, Iris D.] EMMES Corp, DCC, Rockville, MD USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Adult Blood & Marrow Stem Cell Transplant Program, Portland, OR 97201 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bolanos-Meade, Javier] Johns Hopkins, Div Hematol Malignancies, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Brown, Janice M. Y.] Stanford Univ, Dept Med, Div Blood & Marrow Transplantat, Sch Med, Stanford, CA 94305 USA. [Brown, Janice M. Y.] Stanford Univ, Dept Med, Div Infect Dis, Sch Med, Stanford, CA 94305 USA. [Walsh, Thomas J.] Cornell Univ, Program Infect Dis, Weill Cornell Med Ctr, New York, NY 10021 USA. [Walsh, Thomas J.] Cornell Univ, Med Mycol Res Lab, Weill Cornell Med Ctr, New York, NY 10021 USA. [Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Ctr, New York, NY 10021 USA. [Horowitz, Mary H.] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Horowitz, Mary H.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Kurtzberg, Joanne] Duke Univ, Carolinas Cord Blood Bank, Durham, NC USA. [Kurtzberg, Joanne] Duke Univ, Robertson Clin & Translat Cell Therapy Program, Durham, NC USA. [Kurtzberg, Joanne] Duke Univ, Pediat Blood & Marrow Transplant Program, Durham, NC USA. [Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Transplant & Oncol Infect Dis Program, Baltimore, MD USA. [Wingard, John R.] Univ Florida, Div Hematol Oncol, Coll Med, Gainesville, FL USA. [Leather, Helen] Univ Florida, Coll Med, Dept Med, Div Hematol Oncol, Gainesville, FL USA. RP Mauskopf, J (reprint author), RTI Hlth Solut, 200 Pk Dr, Res Triangle Pk, NC USA. EM jmauskopf@rti.org FU National Heart, Lung, and Blood Institute [U10HL069294]; National Cancer Institute; Astellas Pharma US Inc.; Merck Co., Inc.; Pfizer Inc.; Sigma-Tau Pharmaceuticals, Inc. FX Supported by grant U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute.; Dr. Marr is a consultant and serves on advisory boards for Astellas Pharma US Inc., Merck & Co., Inc., and Pfizer Inc. and receives grant support from those companies and Sigma-Tau Pharmaceuticals, Inc. Dr. Mauskopf has previously conducted research for Pfizer Inc., including studies of voriconazole. Dr. Wingard has received lecture fees from Pfizer Inc. and consultant fees from Astellas Pharma US Inc. The other authors have declared no potential conflicts of interest. NR 25 TC 3 Z9 4 U1 0 U2 11 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD SEP 1 PY 2013 VL 70 IS 17 BP 1518 EP 1527 DI 10.2146/ajhp120599 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 210BH UT WOS:000323803800015 PM 23943184 ER PT J AU Gao, YM Moonis, G Cunnane, ME Eisenberg, RL AF Gao, Yiming Moonis, Gul Cunnane, Mary E. Eisenberg, Ronald L. TI Lacrimal Gland Masses SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE lacrimal gland; lacrimal gland masses C1 [Gao, Yiming; Moonis, Gul; Eisenberg, Ronald L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Cunnane, Mary E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02215 USA. RP Eisenberg, RL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM rleisenb@bidmc.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2013 VL 201 IS 3 BP W371 EP W381 DI 10.2214/AJR.12.9553 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 207LP UT WOS:000323601500001 PM 23971467 ER PT J AU Benichou, G Nadazdin, O Cosimi, AB Kawai, T AF Benichou, G. Nadazdin, O. Cosimi, A. B. Kawai, T. TI Successful Tolerance to Fully MHC Disparate Renal Allografts via Donor Hematopoietic Mixed Chimerism in Non-Human Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Letter ID REJECTION C1 [Benichou, G.] Massachusetts Gen Hosp, Dept Surg, Transplantat Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Res Ctr, Boston, MA 02114 USA. EM gbenichou@partners.org FU NIAID NIH HHS [U19 AI102405] NR 5 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2013 VL 13 IS 9 BP 2500 EP 2500 DI 10.1111/ajt.12366 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 208KS UT WOS:000323678200038 PM 23865775 ER PT J AU Gradl, G Pillukat, T Fuchsberger, T Knobe, M Ring, D Prommersberger, KJ AF Gradl, Gertraud Pillukat, Thomas Fuchsberger, Thomas Knobe, Matthias Ring, David Prommersberger, Karl-Josef TI The functional outcome of acute scapholunate ligament repair in patients with intraarticular distal radius fractures treated by internal fixation SO ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY LA English DT Article DE Distal radius intraarticular fracture; Operative treatment; Scapholunate injury ID CT ARTHROGRAPHY; REDUCTION; WRIST; DISSOCIATION; INSTABILITY; INJURIES; COMPLICATIONS; DIAGNOSIS; PALMAR AB Intra-articular fractures of the distal radius (DRF) are associated with a twofold increase in the risk of scapholunate ligament injury (SLI). The aim of this study was to compare functional outcome, pain, and disability between patients with operatively treated DRF and either an acute, repaired scapholunate ligament injury or no ligament injury. We retrospectively analyzed 18 patients with an intraarticular DRF and SLI that was diagnosed and treated (Group I) and compared them with 20 patients with DRF without associated ligament injury (Group II) (20 women, 18 men; average age 55 years, range 19-72). The two cohorts were analyzed for differences in motion, grip strength, pain, Mayo wrist score, and Quick Disabilities of the Arm, Shoulder, and Hand (DASH) score an average of 43 months (range 12-73) after surgery. Radiographic assessment included fracture union, palmar tilt, radial inclination, ulnar variance, intercarpal angles, and arthrosis (according to Knirk and Jupiter). We used T-tests to compare range of motion, grip strength, pain (visual analog scale), DASH scores, and radiographic alignment between cohorts. A Chi-squared analysis was used to determine radiographic differences of arthritis. There were no significant differences in mean range of motion, grip strength, Quick DASH score, Mayo wrist score, pain level, or radiographic arthrosis between cohorts. There was no correlation between radiographic signs of osteoarthritis and the QuickDASH score, and pain level. The outcomes of intraarticular fractures of the distal radius with operatively treated associated SLI are comparable with the outcomes of intraarticular fractures of the distal radius without associated SLI. C1 [Gradl, Gertraud; Knobe, Matthias] Univ Aachen, Dept Trauma & Reconstruct Surg, D-52074 Aachen, Germany. [Gradl, Gertraud; Ring, David] Massachussetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. [Pillukat, Thomas; Fuchsberger, Thomas; Prommersberger, Karl-Josef] Rhon Klinikum AG, Klin Handchirurg, D-97617 Bad Neustadt an der Saale, Germany. RP Gradl, G (reprint author), Univ Aachen, Dept Trauma & Reconstruct Surg, Pauwelstr 30, D-52074 Aachen, Germany. EM ggradl@ukaachen.de NR 29 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0936-8051 J9 ARCH ORTHOP TRAUM SU JI Arch. Orthop. Trauma Surg. PD SEP PY 2013 VL 133 IS 9 BP 1281 EP 1287 DI 10.1007/s00402-013-1797-3 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 207XN UT WOS:000323638100013 PM 23793480 ER PT J AU Sher, L AF Sher, Leo TI Psychological autopsy studies: Past, present, and future SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter ID SUICIDE C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 5 TC 4 Z9 4 U1 0 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD SEP PY 2013 VL 47 IS 9 BP 884 EP 884 DI 10.1177/0004867413479071 PG 1 WC Psychiatry SC Psychiatry GA 208GS UT WOS:000323666500021 PM 23411093 ER PT J AU Phipps, AI Chan, AT Ogino, S AF Phipps, Amanda I. Chan, Andrew T. Ogino, Shuji TI Anatomic subsite of primary colorectal cancer and subsequent risk and distribution of second cancers SO CANCER LA English DT Article DE colorectal cancer; second cancer; metachronous cancer; standardized incidence ratio; tumor subsite ID SURVIVORS; COLON; METAANALYSIS; OUTCOMES; SMOKING; RECTUM; COHORT AB BACKGROUND Individuals with a history of colorectal cancer (CRC) have an increased risk of subsequent cancer. In this study, the authors used cancer registry data to evaluate whether this increased risk of cancer after CRC differed by anatomic subsite of a first CRC. METHODS Individuals diagnosed with a first primary CRC between 1992 and 2009 were identified from 12 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparing the incidence of subsequent cancers in these patients who had an index CRC versus the cancer incidence rates in the general population. SIRs were calculated for cancers at anatomic sites within and outside the colorectum in analyses stratified by subsite of the index CRC. RESULTS Cancer incidence rates were significantly higher in individuals who had a previous CRC than in the general population (SIR, 1.15; 95% CI, 1.13-1.16). Individuals with an index CRC located between the transverse and descending colon experienced the greatest increased risk both overall (SIR, 1.29-1.33) and particularly with respect to the risk of a second CRC (SIR, 2.53-3.35). The incidence of small intestinal cancer was elevated significantly regardless of the index CRC subsite (SIR, 4.31; 95% CI, 3.70-4.77), and the incidence of endometrial cancer was elevated in those who had an index CRC in the proximal colon (SIR, 1.37-1.79). CONCLUSIONS The risk of second cancer after CRC differs by anatomic site of the first tumor and is particularly pronounced for those with prior CRC located in the transverse to descending colon. The mechanisms underlying this pattern of second cancer risk remain unknown. Cancer 2013;119:3140-3147. (c) 2013 American Cancer Society. C1 [Phipps, Amanda I.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Phipps, AI (reprint author), 1100 Fairview Ave North,M4-C308, Seattle, WA 98109 USA. EM aphipps@fhcrc.org FU National Cancer Institute, National Institutes of Health [R25-CA94880, K05-CA152715, R01-CA151993] FX This work was supported by the National Cancer Institute, National Institutes of Health (R25-CA94880 and K05-CA152715 to Dr. Phipps; R01-CA151993 to Dr. Ogino). The National Institutes of Health had no role in the design or conduct of the study. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 21 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2013 VL 119 IS 17 BP 3140 EP 3147 DI 10.1002/cncr.28076 PG 8 WC Oncology SC Oncology GA 202YA UT WOS:000323255600007 PM 23856984 ER PT J AU Taksler, GB Cutler, DM Giovannucci, E Smith, MR Keating, NL AF Taksler, Glen B. Cutler, David M. Giovannucci, Edward Smith, Matthew R. Keating, Nancy L. TI Ultraviolet index and racial differences in prostate cancer incidence and mortality SO CANCER LA English DT Article DE prostate cancer; disparities; vitamins; survival ID SERUM VITAMIN-D; UNITED-STATES; 25-HYDROXYVITAMIN D; RISK; MECHANISMS; EXPOSURE; SUNLIGHT; SKIN AB BACKGROUND Studies suggest that low levels of vitamin D may be associated with prostate cancer, and darker skin reduces the body's ability to generate vitamin D from sunshine. The impact of sunshine on racial disparities in prostate cancer incidence and mortality is unknown. METHODS Using the Surveillance, Epidemiology, and End Results program database, the authors calculated age-adjusted prostate cancer incidence rates among black and white men aged 45 years by race and county between 2000 and 2009 (N=906,381 men). Similarly, county-level prostate cancer mortality rates were calculated from the National Vital Statistics System (N=288,874). These data were linked with the average monthly solar ultraviolet (UV) radiation index by county and data regarding health, wellness, and demographics. Multivariable regression analysis was used to assess whether increases in the UV index (in deciles) moderated the association between black race and the incidence and mortality of prostate cancer. RESULTS Compared with counties in the lowest UV index decile, prostate cancer incidence rates for white and black men were lower in counties with a higher UV index (all Ps0.051). Incidence rates were higher for black men versus white men, but the difference by race was less for counties in the fourth to fifth UV index deciles versus those in the first decile (Ps0.02). Mortality rates also were found to decrease with increasing UV index for white men (Ps0.003), but increase for black men, and an unexplained increase in racial differences in mortality rates was observed with an increasing UV index. CONCLUSIONS Racial disparities in the incidence of prostate cancer were larger in some areas with less sunshine. Additional research should confirm the findings of the current study and assess whether optimizing vitamin D levels among black men can reduce disparities. Cancer 2013;119:3195-3203. (c) 2013 American Cancer Society. C1 [Taksler, Glen B.] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [Taksler, Glen B.] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Cutler, David M.] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA. [Cutler, David M.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. [Cutler, David M.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Taksler, GB (reprint author), NYU, Sch Med, Dept Populat Hlth, 550 1st Ave,TRB-647, New York, NY 10016 USA. EM Glen.Taksler@nyumc.org OI Taksler, Glen/0000-0002-7566-7104 FU Dana-Farber Cancer Institute FX Supported by the A. David Mazzone Research Awards Program of the Dana-Farber Cancer Institute. NR 42 TC 6 Z9 6 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2013 VL 119 IS 17 BP 3195 EP 3203 DI 10.1002/cncr.28127 PG 9 WC Oncology SC Oncology GA 202YA UT WOS:000323255600014 PM 23744754 ER PT J AU Wang, DS Jani, AB Tai, CG Sesay, M Lee, DK Goodman, M Echt, KV Kilbridge, KE Master, VA AF Wang, Daniel S. Jani, Ashesh B. Tai, Caroline G. Sesay, Musu Lee, Daniel K. Goodman, Michael Echt, Katharina V. Kilbridge, Kerry E. Master, Viraj A. TI Severe lack of comprehension of common prostate health terms among low-income inner-city men SO CANCER LA English DT Article DE prostate cancer; patient education; health literacy; informed consent; decision-making ID RADICAL PROSTATECTOMY; PATIENT EDUCATION; CANCER; LITERACY; SOCIETY; BENEFIT AB BACKGROUND Patients diagnosed with prostate cancer are often counseled about treatment options with the use of terms that are part of the core vocabulary of prostate cancer. It is hypothesized that predominantly lower literacy patients would demonstrate a severe lack of comprehension of prostate cancer terms, thus validating the findings of a previous single-institution study. METHODS A previously developed survey was used to evaluate understanding of terms related to urinary, bowel, and sexual function. The survey was administered by trained evaluators at 2 safety net clinics that provide care for low-income, predominantly African American patients. Comprehension was assessed using semiqualitative methods coded by 2 independent investigators. Literacy and numeracy were also evaluated. RESULTS Among 109 patients who completed the study, only 5% understood the function of the prostate, and 15%, 29%, and 32% understood the terms incontinence, urinary function, and bowel habits, respectively. Lower levels of comprehension were observed for compound words, such as vaginal intercourse (58%), versus single words such as intercourse (95%), validating previous work. Median school level was 13 years, yet median literacy level was only ninth grade, and reading level was significantly correlated with comprehension. Only 30% of patients correctly calculated both a fraction and a percent. CONCLUSIONS Lack of comprehension of prostate health terminology is pronounced in this patient population and may be widespread. This lack of comprehension potentially limits the ability of patients to participate in informed decision-making. These results validate the findings of previous studies and supports a continued need for refined methods of prostate cancer education. Cancer 2013;119:3204-3211. (c) 2013 American Cancer Society. C1 [Wang, Daniel S.; Tai, Caroline G.; Sesay, Musu; Lee, Daniel K.; Master, Viraj A.] Emory Univ, Dept Urol, Winship Canc Inst, Sch Med, Atlanta, GA 30322 USA. [Jani, Ashesh B.] Emory Univ, Dept Radiat Oncol, Winship Canc Inst, Sch Med, Atlanta, GA 30322 USA. [Goodman, Michael] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Echt, Katharina V.] Emory Univ, Dept Med, Winship Canc Inst, Sch Med, Atlanta, GA 30322 USA. [Kilbridge, Kerry E.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Kilbridge, Kerry E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. RP Master, VA (reprint author), Emory Univ, Dept Urol, 1365 Clifton Rd NE,Bldg B,Suite 1400, Atlanta, GA 30322 USA. EM vmaster@emory.edu FU Winship Cancer Institute of Emory University FX This work was supported by a Winship Cancer Institute of Emory University Multi-Investigator Research Seed Grant (co-principal investigators: Drs. Master, Jani, and Goodman). NR 27 TC 14 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2013 VL 119 IS 17 BP 3204 EP 3211 DI 10.1002/cncr.28186 PG 8 WC Oncology SC Oncology GA 202YA UT WOS:000323255600015 PM 23733135 ER PT J AU Chan, JA Blaszkowsky, L Stuart, K Zhu, AX Allen, J Wadlow, R Ryan, DP Meyerhardt, J Gonzalez, M Regan, E Zheng, H Kulke, MH AF Chan, Jennifer A. Blaszkowsky, Lawrence Stuart, Keith Zhu, Andrew X. Allen, Jill Wadlow, Raymond Ryan, David P. Meyerhardt, Jeffrey Gonzalez, Marielle Regan, Eileen Zheng, Hui Kulke, Matthew H. TI A prospective, phase 1/2 study of everolimus and temozolomide in patients with advanced pancreatic neuroendocrine tumor SO CANCER LA English DT Article DE everolimus; temozolomide; pancreatic neuroendocrine tumor; phase 1; 2 study; oncology ID ISLET-CELL-CARCINOMA; BEVACIZUMAB; DACARBAZINE; OCTREOTIDE AB BACKGROUND Both everolimus and temozolomide are associated with single-agent activity in patients with pancreatic neuroendocrine tumor (NET). A phase 1/2 study was performed to evaluate the safety and efficacy of temozolomide in combination with everolimus in patients who have advanced pancreatic NET. METHODS Patients were treated with temozolomide at a dose of 150 mg/m(2) per day on days 1 through 7 and days 15 through 21 in combination with everolimus daily in each 28-day cycle. In cohort 1, temozolomide was administered together with everolimus at 5 mg daily. Following demonstration of safety in this cohort, subsequent patients in cohort 2 were treated with temozolomide plus everolimus at 10 mg daily. The duration of temozolomide treatment was limited to 6 months. Patients were followed for toxicity, radiologic and biochemical response, and survival. RESULTS A total of 43 patients were enrolled, including 7 in cohort 1 and 36 in cohort 2. Treatment was associated with known toxicities of each drug; no synergistic toxicities were observed. Among 40 evaluable patients, 16 (40%) experienced a partial response. The median progression-free survival duration was 15.4 months. Median overall survival was not reached. CONCLUSIONS Temozolomide and everolimus can be safely administered together in patients with advanced pancreatic NET, and the combination is associated with encouraging antitumor activity. Future studies evaluating the efficacy of combination therapy compared to treatment with either agent alone are warranted. Cancer 2013;119:3212-3218. (c) 2013 American Cancer Society. C1 [Chan, Jennifer A.; Meyerhardt, Jeffrey; Gonzalez, Marielle; Regan, Eileen; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Jennifer A.; Meyerhardt, Jeffrey; Kulke, Matthew H.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chan, Jennifer A.; Blaszkowsky, Lawrence; Zhu, Andrew X.; Allen, Jill; Wadlow, Raymond; Ryan, David P.; Meyerhardt, Jeffrey; Kulke, Matthew H.] Harvard Univ, Sch Med, Boston, MA USA. [Blaszkowsky, Lawrence; Zhu, Andrew X.; Allen, Jill; Wadlow, Raymond; Ryan, David P.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Stuart, Keith] Lahey Clin Med Ctr, Dept Hematol & Oncol, Burlington, MA 01803 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jang@partners.org FU Novartis; Schering-Plough/Merck FX This work was supported by Novartis and Schering-Plough/Merck. NR 16 TC 25 Z9 25 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2013 VL 119 IS 17 BP 3212 EP 3218 DI 10.1002/cncr.28142 PG 7 WC Oncology SC Oncology GA 202YA UT WOS:000323255600016 PM 23733618 ER PT J AU Cushman-Vokoun, AM Stover, DG Zhao, ZG Koehler, EA Berlin, JD Vnencak-Jones, CL AF Cushman-Vokoun, Allison M. Stover, Daniel G. Zhao, Zhiguo Koehler, Elizabeth A. Berlin, Jordan D. Vnencak-Jones, Cindy L. TI Clinical Utility of KRAS and BRAF Mutations in a Cohort of Patients With Colorectal Neoplasms Submitted for Microsatellite Instability Testing SO CLINICAL COLORECTAL CANCER LA English DT Article DE Allele specific; Missense; Mutation; Transversion; Biomarker ID K-RAS MUTATIONS; MISMATCH REPAIR GENE; III COLON-CANCER; POINT MUTATIONS; V600E MUTATION; STAGE-II; CODON 12; CETUXIMAB; SURVIVAL; DNA AB Mutations in KRAS and BRAF impact response to EGFR-based therapy. One hundred eleven paraffin-embedded tumor specimens submitted for MSI testing were screened for 7 KRAS mutations and the BRAF p.V600E mutation using fluorescent allele-specific PCR. We demonstrate patterns of KRAS and BRAF mutations in microsatellite-stable and -unstable tumors that are relevant and may be applied in the clinical setting. Background: Molecular analysis has become important in colorectal carcinoma (CRC) evaluation. Alterations in KRAS, BRAF, or mismatch repair (MMR) genes may determine therapeutic response or define a hereditary cancer syndrome. Correlation of DNA studies with clinical findings will further clarify the clinical utility of these markers. Patients and Methods: A retrospective study was performed on 111 paraffin-embedded tumor specimens submitted for microsatellite instability (MSI) testing based on clinical history or histologic examination, or both. DNA samples were screened for 7 KRAS mutations and the BRAF p.V600E mutation using fluorescent allele-specific polymerase-chain reaction (PCR) and capillary electrophoresis. Clinical data were collected through chart review. Results: Fifty-eight male and 53 female patients were studied. The incidence of KRAS and BRAF mutations was 49.5% and 7.2%, respectively. Dideoxy sequencing verified KRAS mutation status in 46 of 49 specimens tested. There was a trend toward significance of individual KRAS mutations on survival (P = .003). Dually positive KRAS and MSI tumors exclusively demonstrated p.G12D and p.G13D mutations (G>A transitions). BRAF-mutated tumors were predominantly right-sided and associated with a borderline worse prognosis. Forty-eight percent of tumors with MSI were present in the left colon or rectum. Conclusion: Allele-specific PCR is an accurate and convenient method to assess KRAS and BRAF mutations and may detect mutations not identified by dideoxy sequencing. KRAS mutation status, in conjunction with morphologic or clinical parameters, may be useful in determining whether a tumor should be tested for MSI. MSI testing should not be considered exclusively in right-sided lesions. BRAF analysis may not be useful in rectal adenocarcinomas and should be evaluated in larger studies. (c) 2013 Elsevier Inc. All rights reserved. C1 [Cushman-Vokoun, Allison M.; Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Comprehens Canc Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA. [Stover, Daniel G.; Berlin, Jordan D.] Vanderbilt Univ, Med Ctr, Dept Med, Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN USA. [Zhao, Zhiguo; Koehler, Elizabeth A.] Vanderbilt Univ, Med Ctr, Dept Biostat, Div Canc Biostat,Vanderbilt Ingram Comprehens Can, Nashville, TN USA. [Berlin, Jordan D.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Comprehens Canc Ctr, Div Hematol Oncol, Nashville, TN USA. [Stover, Daniel G.] Massachusetts Gen Hosp, Ctr Canc, Dana Farber Canc Inst Partners CancerCare, Boston, MA USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. RP Cushman-Vokoun, AM (reprint author), 985454 NebraskaMed Ctr, Dept Pathol & Microbiol, Omaha, NE 68105 USA. EM acushman@unmc.edu OI Stover, Daniel/0000-0001-9003-8165 FU NCI NIH HHS [T32 CA009172] NR 52 TC 13 Z9 14 U1 0 U2 9 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD SEP PY 2013 VL 12 IS 3 BP 168 EP 178 DI 10.1016/j.clcc.2013.04.005 PG 11 WC Oncology SC Oncology GA 206TU UT WOS:000323546600004 PM 23773459 ER PT J AU Edwards, EE Despotopulos, LD Carroll, DL AF Edwards, Erica E. Despotopulos, Lisa Davies Carroll, Diane L. TI Changes in Provider Perceptions of Family Presence During Resuscitation SO CLINICAL NURSE SPECIALIST LA English DT Article DE family presence; invasive procedure; resuscitation ID HEALTH-CARE PROVIDERS; CARDIOPULMONARY-RESUSCITATION; ATTITUDES; MEMBERS; UNIT AB Purpose/Objectives: The purpose of this study was to measure changes in perceptions of healthcare providers (HCPs) in the cardiac intensive care unit (CICU) before and after an implementation of an educational program that included approval of a unit-based guideline for family presence (FP) during resuscitation and invasive procedures. Design: A descriptive pretest and posttest design was used to measure changes in perception for FP during resuscitation and invasive procedures. Setting: The setting for this study was a CICU of a large academic medical center. Sample: A convenient sample of HCPs who work in a CICU was included in this study. Methods: Healthcare providers completed the FP scales for confidence and risk-benefit for resuscitation and invasive procedure before and after the implementation of an FP educational program. The program included presentations, discussions, and collaborative guideline development approval with CICU HCPs. Findings: There were 43 HCPs before and 40 HCPs after the FP educational program who completed the FP Confidence and Risk-Benefit Scales. There was improvement in FP Risk Benefit Scale for resuscitation (P < .01), although there was no change in the invasive procedure scale. There was no significant change in confidence for FP for resuscitation or invasive procedures, although there was a trend toward improved scores. There was a significant increase in the number of family members present during resuscitation after the educational program (P < .02). Implications: The conduct of FP educational program and the approval of a unit-based guideline improved HCPs' perception of risk and benefit of FP during resuscitation and the actual presence of family during resuscitation. This effort provided the infrastructure for FP in the CICU and support for further FP efforts. C1 [Edwards, Erica E.; Despotopulos, Lisa Davies] Massachusetts Gen Hosp, Cardiac Intens Care Unit, Boston, MA 02114 USA. [Carroll, Diane L.] Inst Patient Care, Beverly, MA USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. EM dcarroll3@partners.org FU American Association of Critical Care Nurses FX Funding was received from the American Association of Critical Care Nurses. NR 24 TC 6 Z9 7 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD SEP-OCT PY 2013 VL 27 IS 5 BP 239 EP 244 DI 10.1097/NUR.0b013e3182a0ba13 PG 6 WC Nursing SC Nursing GA 206GR UT WOS:000323507400008 PM 23942103 ER PT J AU Scott, SA Sangkuhl, K Stein, CM Hulot, JS Mega, JL Roden, DM Klein, TE Sabatine, MS Johnson, JA Shuldiner, AR AF Scott, S. A. Sangkuhl, K. Stein, C. M. Hulot, J-S Mega, J. L. Roden, D. M. Klein, T. E. Sabatine, M. S. Johnson, J. A. Shuldiner, A. R. TI Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID OF-FUNCTION POLYMORPHISM; ACUTE CORONARY SYNDROMES; CYTOCHROME-P450 2C19 GENOTYPE; CARDIOVASCULAR EVENTS; STENT THROMBOSIS; TREATED PATIENTS; MAJOR DETERMINANT; GENETIC-VARIANTS; PLATO TRIAL; PRASUGREL AB Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet pro drug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org). C1 [Scott, S. A.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA. [Sangkuhl, K.; Klein, T. E.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Stein, C. M.] Vanderbilt Univ, Sch Med, Dept Med & Pharmacol, Div Clin Pharmacol, Nashville, TN 37212 USA. [Hulot, J-S] Univ Paris 06, INSERM, Pitie Salpetriere Univ Hosp, Dept Pharmacol,UMR S956, Paris, France. [Hulot, J-S] Icahn Sch Med Mt Sinai, Cardiovasc Res Ctr, New York, NY USA. [Mega, J. L.; Sabatine, M. S.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Roden, D. M.] Vanderbilt Univ, Sch Med, Off Personalized Med, Dept Med & Pharmacol, Nashville, TN 37212 USA. [Johnson, J. A.] Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA. [Johnson, J. A.] Coll Med, Gainesville, FL USA. [Johnson, J. A.] Univ Florida, Ctr Pharmacogen, Gainesville, FL USA. [Johnson, J. A.] Univ Florida, Coll Pharm, Dept Med Cardiol, Gainesville, FL USA. [Johnson, J. A.] Univ Florida, Coll Med, Gainesville, FL USA. [Shuldiner, A. R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Shuldiner, A. R.] Univ Maryland, Sch Med, Program Genom & Personalized Med, Baltimore, MD 21201 USA. [Shuldiner, A. R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. EM ashuldin@medicine.umaryland.edu RI Hulot, Jean-Sebastien/A-2278-2016 OI Hulot, Jean-Sebastien/0000-0001-5463-6117 FU National Institutes of Health (NIH); NIH [KL2TR000069, R24GM61374, U01HL65962, U19HL065962-10, U01GM074492, U01HL105198, U01GM92666]; Baltimore Veterans Administration Medical Center FX The authors acknowledge the critical input of the Clinical Pharmacogenetics Implementation Consortium (CPIC) of the Pharmacogenomics Research Network and PharmGKB, funded by the National Institutes of Health (NIH). This work was supported in part by NIH grants KL2TR000069 (S.A.S.), R24GM61374 (K.S. and T.E.K.), U01HL65962 (C.M.S.), U19HL065962-10 (D.M.R.), U01GM074492 (J.A.J.), U01HL105198 (A.R.S.), and U01GM92666 (CPIC). A.R.S. also acknowledges support from the Baltimore Veterans Administration Medical Center. NR 40 TC 168 Z9 185 U1 4 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2013 VL 94 IS 3 BP 317 EP 323 DI 10.1038/clpt.2013.105 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 208NR UT WOS:000323686900016 PM 23698643 ER PT J AU Turner, EH AF Turner, Erick H. TI Author's Reply to Shrier: "Publication Bias, With a Focus on Psychiatry: Causes and Solutions" SO CNS DRUGS LA English DT Letter ID TRIALS; PROTOCOLS; OUTCOMES C1 [Turner, Erick H.] Behav Hlth & Neurosci Div, Portland, ME USA. [Turner, Erick H.] Portland VA Med Ctr, Portland, OR 97239 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Pharmacol, Portland, OR 97201 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Ctr Eth Hlth Care, Portland, OR 97201 USA. RP Turner, EH (reprint author), Behav Hlth & Neurosci Div, Portland, ME USA. EM turnere@ohsu.edu RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 7 TC 0 Z9 0 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD SEP PY 2013 VL 27 IS 9 BP 775 EP 776 DI 10.1007/s40263-013-0099-1 PG 2 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 207RJ UT WOS:000323620900009 PM 23907702 ER PT J AU Silva, GS Schwamm, LH AF Silva, Gisele Sampaio Schwamm, Lee H. TI Review of Stroke Center Effectiveness and Other Get with the Guidelines Data SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Stroke; Systems of care; Stroke unit; Emergency medical services; Primary stroke center; Comprehensive stroke center ID ACUTE ISCHEMIC-STROKE; EMERGENCY MEDICAL-SERVICES; TISSUE-PLASMINOGEN ACTIVATOR; BRAIN ATTACK COALITION; QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; HOSPITAL PERFORMANCE; PROGRAM; RECOMMENDATIONS; ASSOCIATION AB A stroke system of care comprises a comprehensive, diverse, longitudinal system that addresses all aspects of stroke care in a coordinated manner. It includes the spectrum of stroke care from primary prevention to activation of emergency medical services, acute care, secondary prevention, rehabilitation and return to the community. Acute care for stroke can be initiated in acute stroke ready hospitals with subsequent transfer to either primary or comprehensive stroke centers. The attributes of an effective stroke system of care include coordinated care, customized to the local environment, able to make the best use of the resources available and that respects and maintains traditions of excellence. Care processes for patients with stroke can be improved through participation in certification and recognition programs such as the American Heart Association's Get With The Guidelines-Stroke program. The final aim of stroke systems should be to integrate prevention and treatment and promote patient access to the best evidence-based care. C1 [Silva, Gisele Sampaio] Hosp Israelita Albert Einstein, Programa Integrado Neurol, Sao Paulo, Brazil. [Silva, Gisele Sampaio] Univ Fed Sao Paulo, UNIFESP, Sao Paulo, Brazil. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Silva, GS (reprint author), 379 Estado Israel St,Apt 41, BR-04002200 Sao Paulo, Brazil. EM giselesampaio@hotmail.com OI Schwamm, Lee/0000-0003-0592-9145 NR 54 TC 4 Z9 4 U1 0 U2 7 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD SEP PY 2013 VL 15 IS 9 AR 350 DI 10.1007/s11883-013-0350-8 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 206DI UT WOS:000323497200003 PM 23892766 ER PT J AU Sosenko, JM Skyler, JS Palmer, JP Krischer, JP Yu, LP Mahon, J Beam, CA Boulware, DC Rafkin, L Schatz, D Eisenbarth, G AF Sosenko, Jay M. Skyler, Jay S. Palmer, Jerry P. Krischer, Jeffrey P. Yu, Liping Mahon, Jeffrey Beam, Craig A. Boulware, David C. Rafkin, Lisa Schatz, Desmond Eisenbarth, George CA Type 1 Diabetes TrialNet Grp Diabet Prevention Trial-Type 1 Stu TI The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients SO DIABETES CARE LA English DT Article ID ANTIBODY-POSITIVE RELATIVES; PREVENTION TRIAL-TYPE-1; 1ST-DEGREE RELATIVES; METABOLIC MARKERS; GLUCOSE-TOLERANCE; INSULIN-SECRETION; NATURAL-HISTORY; CHILDREN; MELLITUS; VALIDATION AB OBJECTIVE We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity.RESULTS The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23-3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P 0.01 for all comparisons).CONCLUSIONS These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D. C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa] Univ Miami, Div Endocrinol, Miami, FL 33152 USA. [Palmer, Jerry P.] Univ Washington, Div Endocrinol Metab & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Krischer, Jeffrey P.; Beam, Craig A.; Boulware, David C.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Yu, Liping; Eisenbarth, George] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, HLA DNA Lab, Denver, CO 80262 USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Schatz, Desmond] Univ Florida, Div Endocrinol, Gainesville, FL USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33152 USA. EM jsosenko@med.miami.edu RI Moore, Daniel/A-4924-2008; Skyler, Jay/F-4211-2016 OI Moore, Daniel/0000-0002-6889-9345; FU National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, HHSN267200800019C]; National Center for Research Resources through Clinical Translational Science Awards [UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, P30-DK-017047]; General Clinical Research Center Award [M01-RR-00400]; JDRF; American Diabetes Association (ADA) FX The sponsor of the trial was the Type 1 Diabetes TrialNet Study Group. The Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreements U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, and U01-DK-085509 and contract HHSN267200800019C; the National Center for Research Resources through Clinical Translational Science Awards UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, and P30-DK-017047 and General Clinical Research Center Award M01-RR-00400; the JDRF; and the American Diabetes Association (ADA). NR 30 TC 38 Z9 38 U1 3 U2 40 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2013 VL 36 IS 9 BP 2615 EP 2620 DI 10.2337/dc13-0425 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 205CZ UT WOS:000323420200048 PM 23818528 ER PT J AU Daniels, M DuBose, SN Maahs, DM Beck, RW Fox, LA Gubitosi-Klug, R Laffel, LM Miller, KM Speer, H Tamborlane, WV Tansey, MJ AF Daniels, Mark DuBose, Stephanie N. Maahs, David M. Beck, Roy W. Fox, Larry A. Gubitosi-Klug, Rose Laffel, Lori M. Miller, Kellee M. Speer, Heather Tamborlane, William V. Tansey, Michael J. CA T1D Exchange Clinic Network TI Factors Associated With Microalbuminuria in 7,549 Children and Adolescents With Type 1 Diabetes in the T1D Exchange Clinic Registry SO DIABETES CARE LA English DT Article ID URINARY ALBUMIN EXCRETION; NATURAL-HISTORY; RISK-FACTORS; NEPHROPATHY; PREVALENCE; DURATION; MELLITUS; COMPLICATIONS; SEX; POPULATION AB OBJECTIVE To examine factors associated with clinical microalbuminuria (MA) diagnosis in children and adolescents in the T1D Exchange clinic registry.RESEARCH DESIGN AND METHODS T1D Exchange participants <20 years of age with type 1 diabetes 1 year and urinary albumin-to-creatinine ratio (ACR) measured within the prior 2 years were included in the analysis. MA diagnosis required all of the following: 1) a clinical diagnosis of sustained MA or macroalbuminuria, 2) confirmation of MA diagnosis by either the most recent ACR being 30 mg/g or current treatment with an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB), and 3) no known cause for nephropathy other than diabetes. Logistic regression was used to assess factors associated with MA.RESULTS MA was present in 329 of 7,549 (4.4%) participants, with a higher frequency associated with longer diabetes duration, higher mean glycosylated hemoglobin (HbA(1c)) level, older age, female sex, higher diastolic blood pressure (BP), and lower BMI (P 0.01 for each in multivariate analysis). Older age was most strongly associated with MA among participants with HbA(1c) 9.5% (80 mmol/mol). MA was uncommon (<2%) among participants with HbA(1c) <7.5% (<58 mmol/mol). Of those with MA, only 36% were receiving ACEI/ARB treatment.CONCLUSIONS Our results emphasize the importance of good glycemic and BP control, particularly as diabetes duration increases, in order to reduce the risk of nephropathy. Since age and diabetes duration are important nonmodifiable factors associated with MA, the importance of routine screening is underscored to ensure early diagnosis and timely treatment of MA. C1 [Daniels, Mark; Speer, Heather] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [DuBose, Stephanie N.; Beck, Roy W.; Miller, Kellee M.] Jaeb Ctr Hlth Res, Tampa, FL USA. [Maahs, David M.] Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Fox, Larry A.] Nemours Childrens Clin, Jacksonville, FL USA. [Gubitosi-Klug, Rose] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Laffel, Lori M.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Tamborlane, William V.] Yale Univ, New Haven, CT USA. [Tansey, Michael J.] Univ Iowa, Iowa City, IA USA. RP DuBose, SN (reprint author), Jaeb Ctr Hlth Res, Tampa, FL USA. EM sdubose@jaeb.org FU Leona M. and Harry B. Helmsley Charitable Trust; Sanofi; Animas; Novo Nordisk; Bayer; Bristol-Myers Squibb; Johnson Johnson; LifeScan/Animas; Eli Lilly; Menarini; Oshadi Administrative Devices; Daiichi Sankyo FX Funding was provided by the Leona M. and Harry B. Helmsley Charitable Trust.; R.W.B.'s nonprofit employer has received consultant payments on his behalf from Sanofi and Animas and a research grant from Novo Nordisk with no personal compensation to R. W. B. L. A. F. has received payments as a clinical advisory board member at Tandem Diabetes Care. L. M. L. has received grant support and consultant payments from Bayer, consultant and advisory board payments from Bristol-Myers Squibb and Sanofi, and consultancy payments from Johnson & Johnson, LifeScan/Animas, Eli Lilly, Menarini, and Oshadi Administrative Devices and also serves on the JDRF International Advisory Board. M.J.T. has received consultancy payments from Daiichi Sankyo. No other potential conflicts of interest relevant to this article were reported. NR 28 TC 16 Z9 17 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2013 VL 36 IS 9 BP 2639 EP 2645 DI 10.2337/dc12-2192 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 205CZ UT WOS:000323420200051 PM 23610082 ER PT J AU Ho, HC Eloubeidi, MA Siddiqui, UD Brugge, WR Rossi, F Bounds, BW Aslanian, HR AF Ho, Henry C. Eloubeidi, Mohamad A. Siddiqui, Uzma D. Brugge, William R. Rossi, Federico Bounds, Brenna W. Aslanian, Harry R. TI Endosonographic and cyst fluid characteristics of cystic pancreatic neuroendocrine tumours: A multicentre case series SO DIGESTIVE AND LIVER DISEASE LA English DT Article DE Cyst fluid analysis; EUS; Fine needle aspiration; Neuroendocrine tumours; Pancreatic cysts ID FINE-NEEDLE-ASPIRATION; PREOPERATIVE DIAGNOSIS; ENDOSCOPIC ULTRASOUND; ENDOCRINE NEOPLASMS; FEATURES; LESIONS; EUS AB Background: Pancreatic neuroendocrine tumours are uncommon neoplasms which may rarely be cystic. Differentiation from other more common cystic neoplasms may be difficult. Aims: To describe the morphologic, cytologic, and cyst fluid characteristics of cystic pancreatic neuroendocrine tumours. Methods: Retrospective analysis of consecutive patients referred for endosonographic evaluation of pancreatic cysts at four centres. Results: 27 patients (12 males) with cystic pancreatic neuroendocrine tumours were identified. Prior to endosonography, this tumour was suspected in only 2 patients based on presenting symptoms (7.4%). The median cyst size was 35 mm (range 8-80 mm). Wall thickening was identified in 13 cases. The median carcinoembryonic antigen level was 1.25 (range 0.6-500). Fine needle aspiration cytology in 17 of 24 patients confirmed neuroendocrine tumour (71%). In 8 of 9 patients who had needle targeting of the cyst wall, cytology was consistent with neuroendocrine tumour (88.9%). 18 patients underwent surgical resection. Conclusions: Cystic pancreatic neuroendocrine tumour was rarely suspected, including by cross-sectional imaging. Wall thickening was identified in approximately half of cases on endosonography. Cyst fluid was typically non-viscous with very low carcinoembryonic antigen levels. Targeting the wall during fine needle aspiration had a high diagnostic yield and should be performed. (c) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. C1 [Ho, Henry C.; Aslanian, Harry R.] Yale Univ, Sch Med, Sect Digest Dis, New Haven, CT USA. [Eloubeidi, Mohamad A.] Amer Univ Beirut, Sch Med, Div Gastroenterol & Hepatol, Beirut, Lebanon. [Siddiqui, Uzma D.] Univ Chicago, Dept Med, Gastroenterol Sect, Chicago, IL 60637 USA. [Brugge, William R.; Bounds, Brenna W.] Harvard Univ, Massachusetts Gen Hosp, Dept Internal Med, GI Unit, Boston, MA 02115 USA. [Rossi, Federico] Minnesota Gastroenterol PA, Minneapolis, MN USA. RP Ho, HC (reprint author), Sect Digest Dis, 333 Cedar St,1080 LMP, New Haven, CT 06520 USA. EM henry.ho@yale.edu NR 19 TC 6 Z9 6 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD SEP PY 2013 VL 45 IS 9 BP 750 EP 753 DI 10.1016/j.dld.2013.02.021 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 207LS UT WOS:000323601900009 PM 23582348 ER PT J AU Meek, TH Matsen, ME Dorfman, MD Guyenet, SJ Damian, V Nguyen, HT Taborsky, GJ Morton, GJ AF Meek, Thomas H. Matsen, Miles E. Dorfman, Mauricio D. Guyenet, Stephan J. Damian, Vincent Nguyen, Hong T. Taborsky, Gerald J., Jr. Morton, Gregory J. TI Leptin Action in the Ventromedial Hypothalamic Nucleus Is Sufficient, But Not Necessary, to Normalize Diabetic Hyperglycemia SO ENDOCRINOLOGY LA English DT Article ID GLUCOSE-UPTAKE; CARDIOVASCULAR ACTIONS; PERIPHERAL-TISSUES; WEIGHT HOMEOSTASIS; INSULIN-RESISTANCE; NERVOUS-SYSTEM; FOOD-INTAKE; RATS; NEURONS; CNS AB In rodent models of type 1 diabetes, leptin administration into brain ventricles normalizes blood glucose at doses that have no effect when given peripherally. The ventromedial nucleus of the hypothalamus (VMN) is a potential target for leptin's antidiabetic effects because leptin-sensitive neurons in this brain area are implicated in glucose homeostasis. To test this hypothesis, we injected leptin directly into the bilateral VMN of rats with streptozotocin-induced uncontrolled diabetes mellitus. This intervention completely normalized both hyperglycemia and the elevated rates of hepatic glucose production and plasma glucagon levels but had no effect on tissue glucose uptake in the skeletal muscle or brown adipose tissue as measured using tracer dilution techniques during a basal clamp. To determine whether VMN leptin signaling is required for leptin-mediated normalization of diabetic hyperglycemia, we studied mice in which the leptin receptor gene was deleted in VMN steroidogenic factor 1 neurons using cre-loxP technology. Our findings indicate leptin action within these neurons is not required for the correction of diabetic hyperglycemia by central leptin infusion. We conclude that leptin signaling in the VMN is sufficient to mediate leptin's antidiabetic action but may not be necessary for this effect. Leptin action within a distributed neuronal network may mediate its effects on glucose homeostasis. C1 [Meek, Thomas H.; Matsen, Miles E.; Dorfman, Mauricio D.; Guyenet, Stephan J.; Damian, Vincent; Nguyen, Hong T.; Morton, Gregory J.] Univ Washington, Diabet & Obes Ctr Excellence, Dept Med, Seattle, WA 98109 USA. [Taborsky, Gerald J., Jr.] Vet Affairs Puget Sound Hlth Care Syst, Dept Vet Affairs Med Ctr, Seattle, WA 98108 USA. RP Morton, GJ (reprint author), Univ Washington South Lake Union, Dept Med, 850 Republican St,N334,Box 358055, Seattle, WA 98195 USA. EM gjmorton@u.washington.edu FU Novo Nordisk Proof-of-Principle Award; National Institutes of Health [DK089053, DK050154]; Nutrition Obesity Research Center [DK035816]; Diabetes and Metabolism Training Grants [F32 DK097859, T32 DK0007247] FX This work was supported by a Novo Nordisk Proof-of-Principle Award (to G.J.M.), National Institutes of Health Grants DK089053 (to G.J.M.), and DK050154 (to G.J.T.), the Nutrition Obesity Research Center Grant DK035816, and the Diabetes and Metabolism Training Grants F32 DK097859 and T32 DK0007247. NR 33 TC 14 Z9 14 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2013 VL 154 IS 9 BP 3067 EP 3076 DI 10.1210/en.2013-1328 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 207RE UT WOS:000323620100012 PM 23782941 ER PT J AU Garcia, JM Scherer, T Chen, JA Guillory, B Nassif, A Papusha, V Smiechowska, J Asnicar, M Buettner, C Smith, RG AF Garcia, Jose M. Scherer, Thomas Chen, Ji-an Guillory, Bobby Nassif, Anriada Papusha, Victor Smiechowska, Joanna Asnicar, Mark Buettner, Christoph Smith, Roy G. TI Inhibition of Cisplatin-Induced Lipid Catabolism and Weight Loss by Ghrelin in Male Mice SO ENDOCRINOLOGY LA English DT Article ID HORMONE-SENSITIVE LIPASE; FATTY-ACID OXIDATION; SKELETAL-MUSCLE; ADIPOSE-TISSUE; CANCER CACHEXIA; METABOLISM; LIPOLYSIS; ANOREXIA; RATS; IDENTIFICATION AB Cachexia, defined as an involuntary weight loss >= 5%, is a serious and dose-limiting side effect of chemotherapy that decreases survival in cancer patients. Alterations in lipid metabolism are thought to cause the lipodystrophy commonly associated with cachexia. Ghrelin has been proposed to ameliorate the alterations in lipid metabolism due to its orexigenic and anabolic properties. However, the mechanisms of action through which ghrelin could potentially ameliorate chemotherapy-associated cachexia have not been elucidated. The objectives of this study were to identify mechanisms by which the chemotherapeutic agent cisplatin alters lipid metabolism and to establish the role of ghrelin in reversing cachexia. Cisplatin-induced weight and fat loss were prevented by ghrelin. Cisplatin increased markers of lipolysis in white adipose tissue (WAT) and of beta-oxidation in liver and WAT and suppressed lipogenesis in liver, WAT, and muscle. Ghrelin prevented the imbalance between lipolysis, beta-oxidation, and lipogenesis in WAT and muscle. Pair-feeding experiments demonstrated that the effects of cisplatin and ghrelin on lipogenesis, but not on lipolysis and beta-oxidation, were due to a reduction in food intake. Thus, ghrelin prevents cisplatin-induced weight and fat loss by restoring adipose tissue functionality. An increase in caloric intake further enhances the anabolic effects of ghrelin. C1 [Garcia, Jose M.; Chen, Ji-an; Guillory, Bobby; Papusha, Victor; Smiechowska, Joanna] Baylor Coll Med, Dept Med & Mol & Cell Biol, Ctr Translat Res Inflammatory Dis, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Garcia, Jose M.; Papusha, Victor; Smiechowska, Joanna; Asnicar, Mark; Smith, Roy G.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Scherer, Thomas; Buettner, Christoph] Mt Sinai Sch Med, Dept Med & Neurosci, New York, NY 10029 USA. [Nassif, Anriada] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. RP Garcia, JM (reprint author), Michael E DeBakey VA Med Ctr, Div Endocrinol Diabet & Metab, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77584 USA. EM jgarcia1@bcm.edu FU US Department of Veterans Affairs (MERIT) [I01-BX000507, I01 CX000174]; US Department of Veterans Affairs (MREP); US Department of Veterans Affairs (SHCNCDA); Caroline Wiess Law Fund for Molecular Medicine; NIH [AG040583, T32AG000183, DK083658, DK082724, DK059637, DK020593]; Irma T. Hirschl Scholar Award; University of Virginia [DK076037]; Baylor Diabetes and Endocrinology Research Center [P30 DK079638]; University of Pittsburgh School of Medicine Dean's Summer Research Program [DK 065521]; [U24 DK59637] FX This work was supported by the US Department of Veterans Affairs (MERIT grants I01-BX000507 and I01 CX000174, MREP, and a SHCNCDA); the Caroline Wiess Law Fund for Molecular Medicine (to J.M.G.) and NIH Grants AG040583 (to J.M.G.), T32AG000183 (to J.M.G. and B. G.), and DK083658 and DK082724 (to C. B.) C. B. is the recipient of an Irma T. Hirschl Scholar Award. The Vanderbilt MMPC was supported in part by U24 DK59637; Vanderbilt University Medical Center Hormone Assay and Analytical Services Core was supported by NIH Grants DK059637 and DK020593; University of Virginia and Baylor Diabetes and Endocrinology Research Center received grants (DK076037 and P30 DK079638, respectively). A.N. received support from the University of Pittsburgh School of Medicine Dean's Summer Research Program T35 Grant DK 065521. NR 41 TC 20 Z9 20 U1 0 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2013 VL 154 IS 9 BP 3118 EP 3129 DI 10.1210/en.2013-1179 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 207RE UT WOS:000323620100017 PM 23832960 ER PT J AU Brugge, WR AF Brugge, William R. TI EUS SO ENDOSCOPY LA English DT Article ID FINE-NEEDLE-ASPIRATION; DIAGNOSTIC YIELD; GALLBLADDER DRAINAGE; FLUID COLLECTIONS; PANCREATIC CYSTS; CONTROLLED-TRIAL; GUIDED DRAINAGE; METAL STENT; FNA; VIDEOS AB EUS has undergone a rapid change in the past few years as the technique has evolved from a primarily imaging modality with radial instruments to an interventional and therapeutic procedure using linear EUS instruments. Digestive Disease Week (DDW) 2013 presented a large number of excellent EUS abstracts. I have selected abstracts from around the world with a range of topics, but focusing on new therapies. C1 Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA 02214 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, Blake 4,55 Fruit St, Boston, MA 02214 USA. EM WBRUGGE@PARTNERS.ORG FU RedPath integrated Pathology FX Dr Brugge received a research grant from RedPath integrated Pathology. NR 38 TC 0 Z9 0 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD SEP PY 2013 VL 45 IS 9 BP 750 EP 755 DI 10.1055/s-0033-1344628 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 208LB UT WOS:000323679200013 PM 23990487 ER PT J AU Liu, JF Tolaney, SM Birrer, M Fleming, GF Buss, MK Dahlberg, SE Lee, H Whalen, C Tyburski, K Winer, E Ivy, P Matulonis, UA AF Liu, Joyce F. Tolaney, Sara M. Birrer, Michael Fleming, Gini F. Buss, Mary K. Dahlberg, Suzanne E. Lee, Hang Whalen, Christin Tyburski, Karin Winer, Eric Ivy, Percy Matulonis, Ursula A. TI A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Olaparib; PARP-inhibitor; Cediranib; Anti-angiogenic; Ovarian; Breast; Phase 1 ID HOMOLOGOUS RECOMBINATION; DOWN-REGULATION; SOLID TUMORS; DNA-REPAIR; BEVACIZUMAB; HYPOXIA; RAD51; BRCA1; CELLS AB Background: Poly(ADP-ribose) polymerase (PARP)-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3 and olaparib, a PARP-inhibitor (NCT01116648). Methods: Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or met Gynecologic Cancer InterGroup (GCIG) CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. Results: 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia >= 4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD) >24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for >24 weeks. Interpretation: The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Liu, Joyce F.; Tolaney, Sara M.; Whalen, Christin; Tyburski, Karin; Winer, Eric; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Birrer, Michael] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Fleming, Gini F.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Buss, Mary K.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Ivy, Percy] NIH, Canc Therapy Evaluat Program, Bethesda, MD USA. RP Liu, JF (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM joyce_liu@dfci.harvard.edu FU Cancer Therapy Evaluation Program of the National Cancer Institute; National Institutes of Health [3 U01 CA062490-16S2] FX This study was sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute and supported by a Grant through the National Institutes of Health (3 U01 CA062490-16S2). The funding source had no role in the conduct, data collection or analysis of the study. NR 23 TC 51 Z9 59 U1 2 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2013 VL 49 IS 14 BP 2972 EP 2978 DI 10.1016/j.ejca.2013.05.020 PG 7 WC Oncology SC Oncology GA 207MM UT WOS:000323604700003 PM 23810467 ER PT J AU Dyer, CA AF Dyer, Christopher A. TI Safety and tolerability of paricalcitol in patients with chronic kidney disease SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE chronic kidney disease; hyperparathyroidism; paricalcitol; proteinuria; vitamin D ID RANDOMIZED CONTROLLED-TRIAL; DOSE VITAMIN-D; PATIENTS RECEIVING HEMODIALYSIS; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; RENAL-FAILURE; CARDIOVASCULAR-DISEASE; DIALYSIS PATIENTS; 19-NOR-1-ALPHA,25-DIHYDROXYVITAMIN D-2; ORAL PARICALCITOL AB Introduction: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD). Beyond skeletal complications, uncontrolled SHPT is associated with cardiovascular mortality. Vitamin D receptor activators (VDRAs) are a mainstay of therapy for SHPT; however, use is limited by hypercalcemia, though less so with calcitriol analogs such as paricalcitol and there is emerging experience with oral formulations for non-SHPT indications. The role of VDRAs in the treatment of SHPT becomes a complex question as alternative strategies have developed. Areas covered: This review summarizes trials that established the safety and efficacy of paricalcitol for SHPT. Comparative experience with paricalcitol as against other VDRAs will be reviewed as will the experience with paricalcitol in non-dialysis CKD and comparative experience with non-VDRA-based therapy. Expert opinion: VDRA therapy is considered first-line therapy for treatment of SHPT. Paricalcitol has demonstrated superiority to calcitriol with respect to parathyroid hormone suppression and calcium-phosphorus balance. Oral formulations of paricalcitol appear to be similarly effective for SHPT. While there is evidence to suggest adjunctive antiproteinuria benefit with the use of VDRAs, efficacy of these agents to slow the progression of CKD or to reduce cardiovascular risk has not yet been demonstrated. C1 Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Dyer, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr,MC 7882, San Antonio, TX 78229 USA. EM DyerCA@uthscsa.edu NR 56 TC 4 Z9 4 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD SEP PY 2013 VL 12 IS 5 BP 717 EP 728 DI 10.1517/14740338.2013.791675 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 206AW UT WOS:000323488900012 PM 23621417 ER PT J AU Shimada, YJ Giugliano, RP AF Shimada, Yuichi J. Giugliano, Robert P. TI Emerging antithrombotic drugs for acute coronary syndrome SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE acute coronary syndrome; cangrelor; myocardial infarction; rivaroxaban; unstable angina; vorapaxar ID PRASUGREL ACHIEVES GREATER; ASPIRIN-TREATED PATIENTS; MYOCARDIAL-INFARCTION; PLATELET INHIBITION; RECEPTOR ANTAGONIST; ANTIPLATELET THERAPY; SECONDARY PREVENTION; HEART-ASSOCIATION; ORAL RIVAROXABAN; ARTERY-DISEASE AB Introduction: Acute coronary syndrome (ACS) encompasses acute myocardial infarction (MI) and unstable angina. Activation of platelets and coagulation cascade plays a central role in the development of ACS. Over the past decade, there have been substantial improvements in the strategies for secondary prevention of ACS, including the development of more potent oral antiplatelet agents such as prasugrel and ticagrelor. However, therapies with even better efficacy and safety profiles and more rapid onset and offset of action would be desirable. Areas covered: This review discusses the advantages and disadvantages of the currently available antithrombotic agents and describes the findings from recent clinical trials of three novel agents; cangrelor (an intravenous P2Y12 receptor antagonist), vorapaxar (protease-activated receptor-1 inhibitor) and rivaroxaban (an oral factor Xa inhibitor). Expert opinion: Cangrelor appears more promising than clopidogrel when a very rapid onset and reversal of antiplatelet effect is needed. Vorapaxar in addition to standard oral antiplatelet therapy was effective in patients with prior MI, but was not safe in patients with a prior stroke. Low dose rivaroxaban decreased cardiovascular events and mortality in patients post-ACS compared to placebo, although bleeding was increased. C1 [Shimada, Yuichi J.; Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med,TIMI Study Grp, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med,TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM rgiugliano@partners.org OI Shimada, Yuichi/0000-0002-3494-307X FU Bristol Myers Squibb; Sanofi; Daiichi-Sankyo; Merck; Johnson and Johnson; Astra-Zeneca FX Shimada has no conflict of interest. Giugliano is a member of the TIMI Study Group, which has received research grant support for clinical trial of antithrombotic drugs in ACSs from Bristol Myers Squibb, Sanofi, Daiichi-Sankyo, Merck, Johnson and Johnson and Astra-Zeneca. He has also received honoraria for CME lectures and/or is consulting for Amgen, Daiichi-Sankyo, Merck and Janssen. NR 41 TC 1 Z9 2 U1 0 U2 14 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD SEP PY 2013 VL 18 IS 3 BP 307 EP 318 DI 10.1517/14728214.2013.819342 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 206NH UT WOS:000323528100005 PM 23848430 ER PT J AU Husain, N Chen, TC Hou, JK AF Husain, Nisreen Chen, Tien-Chun Hou, Jason K. TI An Unusual Cause of Diarrhea in an Immunocompromised Patient Scedosporium apiospermum Colitis and Brain Abscess SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Husain, Nisreen; Chen, Tien-Chun; Hou, Jason K.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Husain, Nisreen; Hou, Jason K.] Baylor Coll Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Chen, Tien-Chun] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Husain, N (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2013 VL 145 IS 3 BP 519 EP + DI 10.1053/j.gastro.2013.06.006 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 207PG UT WOS:000323613700017 PM 23896373 ER PT J AU Sokol, H Conway, KL Zhang, M Choi, M Morin, B Cao, ZF Villablanca, EJ Li, C Wijmenga, C Yun, SH Shi, HN Xavier, RJ AF Sokol, Harry Conway, Kara L. Zhang, Mei Choi, Myunghwan Morin, Bret Cao, Zhifang Villablanca, Eduardo J. Li, Chun Wijmenga, Cisca Yun, Seok Hyun Shi, Hai Ning Xavier, Ramnik J. TI Card9 Mediates Intestinal Epithelial Cell Restitution, T-Helper 17 Responses, and Control of Bacterial Infection in Mice SO GASTROENTEROLOGY LA English DT Article DE Colitis; ILC; Inflammatory Response; Mouse Model ID INNATE LYMPHOID-CELLS; ADAPTER PROTEIN CARD9; INDUCER-LIKE CELLS; CITROBACTER-RODENTIUM; IMMUNE-RESPONSES; NKP46(+) CELLS; HOST-DEFENSE; COLITIS; IL-22; PATHOGENS AB BACKGROUND & AIMS: Caspase recruitment domain 9 (CARD9) is an adaptor protein that integrates signals downstream of pattern recognition receptors. CARD9 has been associated with autoinflammatory disorders, and loss-of-function mutations have been associated with chronic mucocutaneous candidiasis, but the role of CARD9 in intestinal inflammation is unknown. We characterized the role of Card9 in mucosal immune responses to intestinal epithelial injury and infection. METHODS: We induced intestinal inflammation in Card9-null mice by administration of dextran sulfate sodium (DSS) or Citrobacter rodentium. We analyzed body weight, assessed inflammation by histology, and measured levels of cytokines and chemokines using quantitative reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Cell populations were compared between wild-type and Card9-null mice by flow cytometry analysis. RESULTS: Colon tissues and mesenteric lymph nodes of Card9-null mice had reduced levels of interleukin (IL)-6, interferon-gamma, and T-helper (Th) 17 cytokines after administration of DSS, compared with wild-type mice. IL-17A and IL-22 expression were reduced in the recovery phase after DSS administration, coincident with decreased expression of antimicrobial peptides and the chemokine (C-C motif) ligand 20 (Ccl20). Although Card9-null mice had more intestinal fungi based on 18S analysis, their Th17 responses remained defective even when an antifungal agent was administered throughout DSS exposure. Moreover, Card9-null mice had impaired immune responses to C rodentium, characterized by decreased levels of colonic IL-6, IL-17A, IL-22, and regenerating islet-derived 3 gamma (RegIII gamma), as well as fewer IL-22-producing innate lymphoid cells (ILCs) in colon lamina propria. CONCLUSIONS: The adaptor protein CARD9 coordinates Th17- and innate lymphoid cell-mediated intestinal immune responses after epithelial injury in mice. C1 [Sokol, Harry; Conway, Kara L.; Morin, Bret; Cao, Zhifang; Villablanca, Eduardo J.; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Sokol, Harry; Conway, Kara L.; Morin, Bret; Cao, Zhifang; Villablanca, Eduardo J.; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Sokol, Harry; Conway, Kara L.; Morin, Bret; Cao, Zhifang; Villablanca, Eduardo J.; Li, Chun; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Choi, Myunghwan; Yun, Seok Hyun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Sokol, Harry] St Antoine Hosp, AP HP, Dept Gastroenterol, Paris, France. [Conway, Kara L.; Morin, Bret; Xavier, Ramnik J.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Conway, Kara L.; Morin, Bret; Xavier, Ramnik J.] Harvard Univ, Cambridge, MA 02138 USA. [Zhang, Mei; Shi, Hai Ning] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mucosal Immunol Lab, Charlestown, MA USA. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu RI Wijmenga, Cisca/D-2173-2009; Villablanca, Eduardo/E-1380-2016; OI Villablanca, Eduardo/0000-0001-9522-9729; Wijmenga, Cisca/0000-0002-5635-1614; sokol, harry/0000-0002-2914-1822; Choi, Myunghwan/0000-0002-4235-7003 FU French Society of Gastroenterology; Bettencourt Schueller Foundation; Ferring Fellowship; Arthur Sachs Scholarship; Netherlands Organization for Scientific Research; National Institutes of Health [DK083756, DK043351, DK086502, DK060049]; Crohn's and Colitis Foundation of America; Leona M. and Harry B. Helmsley Charitable Trust FX Supported by grants from the French Society of Gastroenterology, the Bettencourt Schueller Foundation, the Ferring Fellowship, and the Arthur Sachs Scholarship (H. S.); The Netherlands Organization for Scientific Research (C. W.); by grants from the National Institutes of Health (DK083756, DK043351, DK086502, and DK060049), the Crohn's and Colitis Foundation of America, and The Leona M. and Harry B. Helmsley Charitable Trust (R.J.X.). NR 45 TC 31 Z9 32 U1 2 U2 24 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2013 VL 145 IS 3 BP 591 EP + DI 10.1053/j.gastro.2013.05.047 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 207PG UT WOS:000323613700028 PM 23732773 ER PT J AU Low, D Tran, HT Lee, IA Dreux, N Kamba, A Reinecker, HC Darfeuille-Michaud, A Barnich, N Mizoguchi, E AF Low, Daren Tran, Hoa T. Lee, In-Ah Dreux, Nicolas Kamba, Alan Reinecker, Hans-Christian Darfeuille-Michaud, Arlette Barnich, Nicolas Mizoguchi, Emiko TI Chitin-Binding Domains of Escherichia Coli ChiA Mediate Interactions With Intestinal Epithelial Cells in Mice With Colitis SO GASTROENTEROLOGY LA English DT Article DE Mouse Model; Ulcerative Colitis; Bacterial Infection; AIEC ID CROHNS-DISEASE; ILEAL MUCOSA; PROMOTER POLYMORPHISMS; BACTERIAL ADHESION; TYPE-1 PILI; COLONIZATION; INFLAMMATION; ADHERENCE; INVASION; LF82 AB BACKGROUND & AIMS: Inducible chitinase 3-like-1 is expressed by intestinal epithelial cells (IECs) and adheres to bacteria under conditions of inflammation. We performed a structure-function analysis of the chitin-binding domains encoded by the chiA gene, which mediates the pathogenic effects of adherent invasive Escherichia coli (AIEC). METHODS: We created AIEC (strain LF82) with deletion of chiA (LF82-Delta chiA) or that expressed chiA with specific mutations. We investigated the effects of infecting different IEC lines with these bacteria compared with nonpathogenic E coli; chitinase activities were measured using the colloidal chitin-azure method. Colitis was induced in C57/Bl6 mice by administration of dextran sodium sulfate, and mice were given 10(8) bacteria for 15 consecutive days by gavage. Stool/tissue samples were collected and analyzed. RESULTS: LF82-Delta chiA had significantly less adhesion to IEC lines than LF82. Complementation of LF82-Delta chiA with the LF82 chiA gene, but not chiA from nonpathogenic (K12) E coli, increased adhesion. We identified 5 specific polymorphisms in the chitin-binding domain of LF82 chiA (at amino acids 362, 370, 378, 388, and 548) that differ from chiA of K12 and were required for LF82 to interact directly with IECs. This interaction was mediated by an N-glycosylated asparagine in chitinase 3-like-1 (amino acid 68) on IECs. Mice infected with LF82, or LF82-Delta chiA complemented with LF82 chiA, developed more severe colitis after administration of dextran sodium sulfate than mice infected with LF82-Delta chiA or LF82 that expressed mutant forms of chiA. CONCLUSIONS: AIEC adheres to an N-glycosylated chitinase 3-like-1 on IECs via the chitin-binding domain of chiA. This mechanism promotes the pathogenic effects of AIEC in mice with colitis. C1 [Low, Daren; Tran, Hoa T.; Lee, In-Ah; Kamba, Alan; Reinecker, Hans-Christian; Mizoguchi, Emiko] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Low, Daren; Tran, Hoa T.; Lee, In-Ah; Kamba, Alan; Reinecker, Hans-Christian; Mizoguchi, Emiko] Harvard Univ, Sch Med, Boston, MA USA. [Dreux, Nicolas; Darfeuille-Michaud, Arlette; Barnich, Nicolas] Univ Auvergne, INSERM, UMR1071, M2iSH, Clermont Ferrand, France. [Dreux, Nicolas; Darfeuille-Michaud, Arlette; Barnich, Nicolas] USC INRA 2018, Clermont Ferrand, France. [Reinecker, Hans-Christian; Mizoguchi, Emiko] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Darfeuille-Michaud, Arlette] Ctr Hosp Univ, Clermont Ferrand, France. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, GRJ 825D, Boston, MA 02114 USA. EM emizoguchi@partners.org FU National Institute of Health [DK80070, DK74454, DK64289, DK43351, DK068181, DK033506, AI093588]; Broad Medical Foundation; American Gastroenterological Association Foundation; A*STAR Graduate Academy (Singapore); National Research Foundation of Korea; INSERM [UMR1071]; INRA [USC-2018]; Association F. Aupetit (AFA); Region Auvergne (Nouveau Chercheur) FX This work has been supported by National Institute of Health (DK80070, DK74454, DK64289, and DK43351, DK068181, DK033506, and AI093588), and grants from the Broad Medical Foundation and American Gastroenterological Association Foundation to EM. DL has been awarded the fellowship grant supported by A*STAR Graduate Academy (Singapore) and I-AL was supported by the National Research Foundation of Korea. This study was also supported by INSERM (UMR1071), INRA (USC-2018) and by grants from the Association F. Aupetit (AFA) and Region Auvergne (Nouveau Chercheur). NR 31 TC 14 Z9 15 U1 2 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2013 VL 145 IS 3 BP 602 EP + DI 10.1053/j.gastro.2013.05.017 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 207PG UT WOS:000323613700029 PM 23684751 ER PT J AU Cohn, DE Leitao, M Levenback, C Berkowitz, R Roman, L Lucci, J Kim, S Lancaster, J Odunsi, K Wakabayashi, M Goff, BA AF Cohn, David E. Leitao, Mario Levenback, Charles Berkowitz, Ross Roman, Lynda Lucci, Joseph Kim, Sarah Lancaster, Johnathan Odunsi, Kunle Wakabayashi, Mark Goff, Barbara A. TI Reporting of quality measures in gynecologic oncology programs at Prospective Payment System (PPS)-Exempt Cancer Hospitals: An early glimpse into a challenging initiative SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Quality measures; PPS-exempt; Affordable Care Act AB Objective. The Affordable Care Act mandates the Prospective Payment System (PPS)-Exempt Cancer Hospitals Quality Reporting program. These 11 hospitals (which are paid fee-for-service rather than on a DRG system) began reporting measures (2 general safety, 2 breast, I colon) in 2013. Given this reporting mandate, we set out to determine whether the PPS-exempt gynecologic oncology programs could identify quality measures specific to the care of our patients. Methods. A list of 12 quality measures specific to gynecologic oncology was created (from sources including the National Quality Forum and the SGO). Measures already in use were not included. The list was ranked by the gynecologic oncology program directors at the PPS-exempt hospitals. Descriptive statistics (including mean and SD for rankings) were utilized. Results. Despite mandatory reporting of quality measures for PPS-exempt cancer hospitals, little consensus exists regarding specific gynecologic cancer measures. Documentation of debulking status, cancer survival, and offering minimally invasive surgery (for endometrial cancer) and intraperitoneal chemotherapy (for ovarian cancer) are important, but with widely variable responses (when ranked 1-12, standard deviations are 2-3). General issues regarding adherence to guidelines for the use of GCSF, documentation of functional status, and tracking of patient satisfaction scores were ranked the lowest. Three of the directors reported that their compensation is partially linked to quality outcomes. Conclusions. There is wide variability in ranking of quality measures, and may relate to provider or institutional factors. Despite the mandatory reporting in PPS-exempt cancer hospitals, work remains to define gynecologic cancer quality measures. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved. C1 [Cohn, David E.] Ohio State Univ, Columbus, OH 43210 USA. [Leitao, Mario] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Levenback, Charles] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Berkowitz, Ross] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roman, Lynda] USC Norris Canc Ctr, Los Angeles, CA USA. [Lucci, Joseph] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Kim, Sarah] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Lancaster, Johnathan] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Odunsi, Kunle] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Wakabayashi, Mark] City Hope Natl Med Ctr, Duarte, CA USA. [Goff, Barbara A.] Univ Washington, Sch Med, Seattle, WA USA. RP Cohn, DE (reprint author), 320 West 10th Ave,M-210 Starling Loving Hall, Columbus, OH 43210 USA. EM David.Cohn@osumc.edu NR 9 TC 6 Z9 6 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2013 VL 130 IS 3 BP 403 EP 406 DI 10.1016/j.ygyno.2013.05.026 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 208OB UT WOS:000323687900002 PM 23718934 ER PT J AU Clark, RM Growdon, WB Wiechert, A Boruta, D Del Carmen, M Goodman, AK Bradford, L Rauh-Hain, A Schorge, JO AF Clark, Rachel M. Growdon, Whitfield B. Wiechert, Andrew Boruta, David Del Carmen, Marcela Goodman, Anne Kathryn Bradford, Leslie Rauh-Hain, Alejandro Schorge, John O. TI Patient, treatment and discharge factors associated with hospital readmission within 30 days after surgical cytoreduction for epithelial ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Readmission; Cytoreduction; Outcomes; Quality ID SURGERY; QUALITY; PROGRAM AB Objective. Hospital readmissions are common, costly and increasingly viewed as adverse events. In gynecologic oncology, data on readmissions are limited. The goal of this study was to examine the patient, treatment and discharge factors associated with unplanned readmission after cytoreductive surgery. Methods. We identified all patients with stages II-IV ovarian cancer who underwent surgical cytoreduction at our institution between 2003 and 2011. A retrospective chart review was performed, and clinical variables were extracted. Utilizing linear and logistic regression, these clinical variables were correlated with risk of readmission. Results. A total of 460 patients were included in the analysis, with the majority having a stage IIIC high grade serous cancer. Optimal cytoreduction (<1.0 cm residual disease) was obtained in 368 patients (81%), and 233 patients (50%) underwent at least one radical procedure. Perioperative complications were observed in 148 patients (32%). A large proportion of our cohort was discharged to rehabilitation facilities (12%) or with a visiting nurse (38%). Fifty five patients (12%) were readmitted within 30 days. On multivariate logistic regression, reoperation and perioperative cardiopulmonary event were the only factors associated with readmission (OR = 3.2, 95% CI = 1.7-6.0). Discharge home with ancillary services was not protective against readmission, even when controlling for perioperative complications (OR = 1.18, 95% CI = 0.53-2.64). Conclusions. Readmission after surgical cytoreduction affected 12% of our population. Multivariate analyses suggested perioperative complications, particularly reoperation and cardiopulmonary event, placed the patient at the greatest risk Age, comorbidities, surgical radicality and discharge with visiting nurse services/ rehabilitation facility did not affect the likelihood of readmission. (C) 2013 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Clark, RM (reprint author), 4 Longfellow Pl Apt 2703, Boston, MA 02114 USA. EM rmclark@partners.org NR 14 TC 17 Z9 17 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2013 VL 130 IS 3 BP 407 EP 410 DI 10.1016/j.ygyno.2013.05.034 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 208OB UT WOS:000323687900003 PM 23747329 ER PT J AU Diver, E May, T Vargas, R Bernstein, M Goldstein, D Berkowitz, R AF Diver, Elisabeth May, Taymaa Vargas, Roberto Bernstein, Marilyn Goldstein, Donald Berkowitz, Ross TI Changes in clinical presentation of postterm choriocarcinoma at the New England Trophoblastic Disease Center in recent years SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Postterm Choriocarcinoma; GTN; Trophoblastic ID TERM GESTATION; MANAGEMENT; PREGNANCY; NEOPLASIA AB Objective. To review the last 15 year experience of choriocarcinoma following a term gestation at the New England Trophoblastic Disease Center (NETDC) and compare these results to earlier data to determine any changes in the clinical presentation and outcome of this disease. Methods. Women with postterm choriocarcinoma from 1996 through 2011 followed by the NETDC were identified by diagnosis codes. Twenty charts were identified and reviewed. These data were then compared to published results from the NETDC of 44 women from 1964 to 1996. Results. Time from antecedent pregnancy to diagnosis of choriocarcinoma was significantly longer in the current series, 46.1 vs. 19.7 weeks (p = 0.03). Despite this change, patient outcomes remained comparable, with similar overall mortality rates (13% vs. 10%, p = NS). However, patient presentation was notably different. In the early series, five (11%) infants suffered hydrops or stillbirth, while in the recent series there were no adverse infant outcomes (p = 0.08). Six women in the current series presented in the absence of symptoms suspicious for choriocarcinoma (either by an incidental positive pregnancy test without other symptoms or by placental pathology), compared to one woman in the prior series (30% vs. 2%, p = 0.001). Conclusions. In recent years postterm choriocarcinoma is being diagnosed or referred later after the antecedent pregnancy at our regional referral center. Recent patients more commonly have no other symptoms than a question of pregnancy and are less likely diagnosed due to the presence of fetal hydrops or stillbirth. Despite later diagnoses, survival with postterm choriocarcinoma continues to be high. (C) 2013 Elsevier Inc. All rights reserved. C1 [Diver, Elisabeth; Vargas, Roberto] Brigham & Womens Hosp, Massachusetts Gen Hosp, Integrated Residency Program Obstet & Gynecol, Boston, MA 02115 USA. [May, Taymaa; Bernstein, Marilyn; Goldstein, Donald; Berkowitz, Ross] Brigham & Womens Hosp, Boston, MA 02115 USA. [May, Taymaa; Bernstein, Marilyn; Goldstein, Donald; Berkowitz, Ross] Dana Farber Canc Inst, Dept Obstet & Gynecol, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Boston, MA 02115 USA. [Goldstein, Donald] Harvard Univ, Sch Med, Trophoblast Tumor Registry, Boston, MA 02115 USA. RP Berkowitz, R (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St,CWN 3, Boston, MA 02115 USA. EM ediver@partners.org; tmay1@partners.org; rjv3@partners.org; Marilyn_Bernstein@dfci.harvard.edu; dgoldstein@partners.org; RBerkowitz@partners.org NR 17 TC 2 Z9 3 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2013 VL 130 IS 3 BP 483 EP 486 DI 10.1016/j.ygyno.2013.06.014 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 208OB UT WOS:000323687900017 PM 23777658 ER PT J AU Viswanathan, AN Pinto, AP Schultz, D Berkowitz, R Crum, CP AF Viswanathan, Akila N. Pinto, Alvaro P. Schultz, Delray Berkowitz, Ross Crum, Christopher P. TI Relationship of margin status and radiation dose to recurrence in post-operative vulvar carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Vulvar neoplasms; Radiotherapy; Margin status ID SQUAMOUS-CELL CARCINOMA; RADICAL WIDE EXCISION; INGUINAL LYMPHADENECTOMY; PROGNOSTIC-FACTORS; THERAPY; CANCER; SURVIVAL; CHEMOTHERAPY; VULVECTOMY; MANAGEMENT AB Objective. To evaluate the effect of margin status and radiation dose in patients treated with radiation therapy (RT) for vulvar cancer. Clinical outcomes included vulvar recurrence (VR), relapse-free survival (RFS) and overall survival (OS). Methods. We retrospectively reviewed the records of 300 patients with Stage I-IVA vulvar cancer treated between 1988 and 2009. Slides were reviewed and margin status was scored as negative (>= 1 cm), close (<1 cm) or positive after formalin fixation. Cox proportional hazards models were constructed to determine significant prognostic factors for vulvar relapse. Results. Of 205 eligible patients, 69 (34%) had negative surgical margins, 116(56%) had close margins and 20 (10%) had positive margins. Median follow-up time was 49 months. The 4-year RFS rate was 53% and OS was 73%. Of 78 recurrences, 62 had the vulva as the first site of recurrence. The 4-year rates of freedom from vulvar recurrence were 82%, 63% and 37% for those with negative, close and positive margins, respectively (p for trend = 0.005). On multivariate analysis, close margins (HR = 3.03, 95% CI 1.46-6.26) and positive margins (HR = 7.02, 95% Cl 2.66-18.54) were associated with a significantly increased risk of vulvar relapse. Those who received a dose >= 56 Gy had a lower risk of relapse than those who received <= 50.4 Gy (p < 0.05). Though recurrences were noted with margins up to 9 mm, the highest risk of vulvar recurrence was associated with margins <= 5 mm (p = 0.002). Conclusions. Close or positive margins were associated with a significantly increased risk of vulvar recurrence. Radiation with a dose >= 56 Gy may decrease the risk of vulvar recurrence. (C) 2013 Elsevier Inc. AlFrights reserved. C1 [Viswanathan, Akila N.] Brigham & Womens Hospita, Dept Radiat Oncol, Boston, MA USA. [Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pinto, Alvaro P.; Crum, Christopher P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Schultz, Delray] Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. [Berkowitz, Ross] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 20 TC 16 Z9 18 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2013 VL 130 IS 3 BP 545 EP 549 DI 10.1016/j.ygyno.2013.05.036 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 208OB UT WOS:000323687900027 PM 23747330 ER PT J AU Ather, S Bavishi, C McCauley, MD Dhaliwal, A Deswal, A Johnson, S Chan, W Aguilar, D Pritchett, AM Ramasubbu, K Wehrens, XHT Bozkurt, B AF Ather, Sameer Bavishi, Chirag McCauley, Mark D. Dhaliwal, Amandeep Deswal, Anita Johnson, Sarah Chan, Wenyaw Aguilar, David Pritchett, Allison M. Ramasubbu, Kumudha Wehrens, Xander H. T. Bozkurt, Biykem TI Worsening renal function is not associated with response to treatment in acute heart failure SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE BNP; Renal function; Heart failure ID BRAIN NATRIURETIC PEPTIDE; SERUM CREATININE; CARDIORENAL INTERACTIONS; HOSPITALIZED-PATIENTS; OUTCOMES; IMPACT; ADMISSION AB Background: About a fourth of acute decompensated heart failure (ADHF) patients develop renal dysfunction during their admission. To date, the association of ADHF treatment with the development of worsening renal function (WRF) remains contentious. Thus, we examined the association of WRF with changes in BNP levels and with mortality. Methods: We performed retrospective chart review of patients admitted with ADHF who had BNP, eGFR, creatinine and blood urea nitrogen (BUN) values measured both on admission and discharge. Survival analysis was conducted using Cox proportional hazards model and correlation was measured using Spearman's rank correlation test. Results: 358 patients admitted for ADHF were evaluated. WRF was defined as >20% reduction in eGFR from admission to discharge and response to treatment was assessed by Delta BNP. There was a statistically significant reduction in BNP and increase in BUN during the admission. Delta BNP did not correlate with either Delta GFR or Delta BUN. Patients who developed WRF and those who did not, had a similar reduction in BNP. On univariate survival analysis, Delta BUN, but not Delta eGFR, was associated with 1-year mortality. In multivariate Cox proportional hazards model, BUN at discharge was associated with 1-year mortality (HR: 1.02, p<0.001), but Delta eGFR and Delta BUN were not associated with the primary endpoint. Conclusion: During ADHF treatment, Delta BNP was not associated with changes in renal function. Development of WRF during ADHF treatment was not associated with mortality. Our study suggests that development of WRF should not preclude diuresis in ADHF patients in the absence of volume depletion. (C) 2012 Published by Elsevier Ireland Ltd. C1 [Ather, Sameer; McCauley, Mark D.; Deswal, Anita; Aguilar, David; Pritchett, Allison M.; Ramasubbu, Kumudha; Wehrens, Xander H. T.; Bozkurt, Biykem] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Bavishi, Chirag; Chan, Wenyaw] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Dhaliwal, Amandeep] Univ Iowa, Dept Med, Cardiol Sect, Iowa City, IA 52242 USA. [Deswal, Anita; Johnson, Sarah; Bozkurt, Biykem] Baylor Coll Med, DeBakey VA Med Ctr, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Bozkurt, B (reprint author), Michael E DeBakey VA Med Ctr, Div Cardiol, Winters Ctr Heart Failure, 3C-310 F,2002 Holcombe Blvd, Houston, TX 77030 USA. EM bbozkurt@bcm.edu OI ather, sameer/0000-0002-5579-0658 FU American Heart Association SCA predoctoral fellowship; Alkek foundation fellowship FX S.A. is supported by American Heart Association SCA predoctoral fellowship (2010-2012) and Alkek foundation fellowship (2009-2012). NR 22 TC 8 Z9 8 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 1 PY 2013 VL 167 IS 5 BP 1912 EP 1917 DI 10.1016/j.ijcard.2012.05.004 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207AU UT WOS:000323569600048 PM 22633437 ER PT J AU Harbaugh, MP Manuck, SB Jennings, JR Conklin, SM Yao, JK Muldoon, MF AF Harbaugh, Matthew P. Manuck, Stephen B. Jennings, J. Richard Conklin, Sarah M. Yao, Jeffrey K. Muldoon, Matthew F. TI Long-chain, n-3 fatty acids and physical activity - Independent and interactive associations with cardiac autonomic control SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE n-3 fatty acids; Exercise; HRV ID HEART-RATE-VARIABILITY; MYOCARDIAL-INFARCTION; FISH-OIL; HEALTHY-VOLUNTEERS; COLLEGE ALUMNI; EXERCISE; BLOOD; MORTALITY; RISK; OMEGA-3-FATTY-ACIDS AB Background/objectives: Intake of the marine-based, n-3 fatty acids and engagement in physical activity are inversely related to cardiac morbidity and mortality. Among putative mechanisms, both n-3 fatty acids and physical activity may act through modulation of autonomic control of the cardiovascular system. This investigation examined the independent and interactive associations of n-3 fatty acids (eicosapentaenoic and docosahexanenoic acid; EPA, DHA) and physical activity with heart rate variability (HRV). Methods: Subjects were 259 healthy 30-54 year-old adults. Serum phospholipid fatty acid composition was employed as a biomarker of dietary n-3 fatty acid exposure. Physical activity based on the Paffenbarger questionnaire was coded as < or >= 2000 kcal/week. Standard time-domain (standard deviation of normal-to-normal intervals and root-mean squared of successive differences; SDNN, RMSSD) and frequency domain (high frequency and low frequency power) measures of HRV were derived from resting electrocardiographic recordings. Results: In linear regression models with covariate adjustment for age, gender and race, greater n-3 fatty acid exposure was associated with greater SDNN and RMSSD, and high physical activity was associated with greater RMSSD. n-3 fatty acid exposure also predicted variation in SDNN, RMSSD, and high-frequency power in interaction with physical activity. Specifically, n-3 fatty acid exposure covaried positively with these three HRV indices only among participants expending 2000 kcal per week or more in physical activity. These latter findings were noted for DHA but not EPA. Conclusions: These results suggest that the cardiovascular benefits of n-3 fatty acid consumption may be mediated, in part, by effects on cardiac autonomic control and may be dependent upon concomitant habitual exercise. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Harbaugh, Matthew P.] UPMC St Margarets, Pittsburgh, PA USA. [Manuck, Stephen B.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Jennings, J. Richard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Conklin, Sarah M.] Allegheny Coll, Dept Psychol, Meadville, PA 16335 USA. [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Muldoon, Matthew F.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. RP Muldoon, MF (reprint author), Univ Pittsburgh, Old Engn Hall,Room 506, Pittsburgh, PA 15260 USA. EM mfm10@pitt.edu FU US Public Health Service Awards [T32 HL07560, P01 HL40962, R21 HL081282] FX US Public Health Service Awards T32 HL07560, P01 HL40962, and R21 HL081282. NR 44 TC 1 Z9 1 U1 0 U2 11 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 1 PY 2013 VL 167 IS 5 BP 2102 EP 2107 DI 10.1016/j.ijcard.2012.05.110 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207AU UT WOS:000323569600078 PM 22704872 ER PT J AU Silva-Tinoco, R Ortiz, OC Castillo-Martinez, L Orea-Tejeda, A Navarro, AN Reza-Albarran, A Keirns-Davies, C Tellez-Olvera, L AF Silva-Tinoco, Ruben Carrasco Ortiz, Olin Castillo-Martinez, Lilia Orea-Tejeda, Arturo Navarro Navarro, Adolfo Reza-Albarran, Alfredo Keirns-Davies, Candace Tellez-Olvera, Laura TI Persistence of thyroid hormones disorders in chronic heart failure out patients: "Heart hypothyroidism" SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Thyroid hormones disorders; Chronic heart failure; Heart hypothyroidism ID TRIIODOTHYRONINE LEVELS C1 [Silva-Tinoco, Ruben] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Internal Med, Mexico City, DF, Mexico. [Carrasco Ortiz, Olin; Castillo-Martinez, Lilia; Orea-Tejeda, Arturo; Navarro Navarro, Adolfo; Tellez-Olvera, Laura] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Mexico City, DF, Mexico. [Reza-Albarran, Alfredo] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol, Mexico City, DF, Mexico. [Keirns-Davies, Candace] Massachusetts Gen Hosp, Interpreter Serv, Boston, MA 02114 USA. RP Orea-Tejeda, A (reprint author), Prov 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. EM artorea@yahoo.com.mx RI Castillo-Martinez, Lilia/H-3750-2013 NR 9 TC 0 Z9 0 U1 2 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 1 PY 2013 VL 167 IS 5 BP 2359 EP 2360 DI 10.1016/j.ijcard.2012.11.058 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 207AU UT WOS:000323569600133 PM 23228214 ER PT J AU Suffoletto, B Akers, A McGinnis, KA Calabria, J Wiesenfeld, HC Clark, DB AF Suffoletto, Brian Akers, Aletha McGinnis, Kathleen A. Calabria, Jaclyn Wiesenfeld, Harold C. Clark, Duncan B. TI A Sex Risk Reduction Text-Message Program for Young Adult Females Discharged From the Emergency Department SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Young adult; Health promotion; Sexual health; Text messaging ID RANDOMIZED CONTROLLED-TRIAL; SEXUALLY-TRANSMITTED-DISEASES; UNITED-STATES; HEALTH-CARE; BEHAVIOR; ADOLESCENTS; SERVICE; PEOPLE; SMS; INTERVENTIONS AB Purpose: To pilot test a text message (SMS) sex risk reduction program among at-risk young adult female patients discharged from an emergency department (ED). Methods: A convenience sample of 52 female patients with hazardous drinking behavior and recent risky sexual encounters were recruited from an urban ED and randomized to the SMS program (n = 23) or a control group (n = 29). All participants completed a web-based questionnaire in the ED and at 3-month follow-up. For 12 weeks, SMS participants were asked to report whether they had a risky sexual encounter in the past week, received theory-based feedback, and were asked if they were willing set a goal to refrain from having another risky encounter. Results: Thirty-nine percent of SMS participants completed all weeks of SMS reports, and non-completion increasing from 12% on week 1 to a 33% by week 12. Three-month follow-up was completed in 56% of participants. In the intervention group, there was an increase in the proportion with condom use with last vaginal sex from 20% (95% CI 4%-48%) to 53% (95% CI 27%-79%) and an increase in always condom use over the past 28 days from 0% (95% CI 0%-22%) to 33% (95% CI 12%-62%). These changes were not statistically different from control participants. Conclusions: SMS programs may be useful to reduce risk for sexually transmitted diseases among at-risk young adults being discharged from the ED. Future trials should examine ways to improve adherence to SMS dialog over time and measure objective outcomes in a larger sample. (C) 2013 Society for Adolescent Health and Medicine. All rights reserved. C1 [Suffoletto, Brian; Calabria, Jaclyn] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA 15221 USA. [Akers, Aletha; Wiesenfeld, Harold C.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15221 USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Clark, Duncan B.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15221 USA. RP Suffoletto, B (reprint author), Univ Pittsburgh, 3600 Forbes Ave,Iroquois Bldg,Suite 400A, Pittsburgh, PA 15221 USA. EM suffbp@upmc.edu FU EMF-Century Council; Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program; [R01AA016482]; [P50DA05605] FX The authors thank Jack Doman in the Office of Academic Computing at the Western Psychiatric Institute at the University of Pittsburgh for all computer programming support. B. S. is supported by an EMF-Century Council grant, A. A. is supported by the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program, and D.B.C. is supported by R01AA016482 and P50DA05605. NR 38 TC 17 Z9 17 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2013 VL 53 IS 3 BP 387 EP 393 DI 10.1016/j.jadohealth.2013.04.006 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 207MA UT WOS:000323602900014 PM 23707402 ER PT J AU Tse, SM Gold, DR Sordillo, JE Hoffman, EB Gillman, M Rifas-Shiman, SL Fuhlbrigge, AL Tantisira, KG Weiss, ST Litonjua, AA AF Tse, Sze Man Gold, Diane R. Sordillo, Joanne E. Hoffman, Elaine B. Gillman, MatthewW. Rifas-Shiman, Sheryl L. Fuhlbrigge, Anne L. Tantisira, Kelan G. Weiss, Scott T. Litonjua, Augusto A. TI Diagnostic accuracy of the bronchodilator response in children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; bronchodilator response; diagnosis ID OBSTRUCTIVE AIRWAYS DISEASE; ASTHMA MANAGEMENT PROGRAM; CHILDHOOD ASTHMA; LUNG-FUNCTION; PREDICTORS; RESPONSIVENESS AB Background: The bronchodilator response (BDR) reflects the reversibility of airflow obstruction and is recommended as an adjunctive test to diagnose asthma. The validity of the commonly used definition of BDR, a 12% or greater change in FEV1 from baseline, has been questioned in childhood. Objectives: We sought to examine the diagnostic accuracy of the BDR test by using 3 large pediatric cohorts. Methods: Cases include 1041 children with mild-to-moderate asthma from the Childhood Asthma Management Program. Control subjects (nonasthmatic and nonwheezing) were chosen from Project Viva and Home Allergens, 2 population-based pediatric cohorts. Receiver operating characteristic curves were constructed, and areas under the curve were calculated for different BDR cutoffs. Results: A total of 1041 cases (59.7% male; mean age, 8.9 +/- 2.1 years) and 250 control subjects (46.8% male; mean age, 8.7 +/- 1.7 years) were analyzed, with mean BDRs of 10.7% +/- 10.2% and 2.7% +/- 8.4%, respectively. The BDR test differentiated asthmatic patients from nonasthmatic patients with a moderate accuracy (area under the curve, 73.3%). Despite good specificity, a cutoff of 12% was associated with poor sensitivity (35.6%). A cutoff of less than 8% performed significantly better than a cutoff of 12% (P = .03, 8% vs 12%). Conclusions: Our findings highlight the poor sensitivity associated with the commonly used 12% cutoff for BDR. Although our data show that a threshold of less than 8% performs better than 12%, given the variability of this test in children, we conclude that it might be not be appropriate to choose a specific BDR cutoff as a criterion for the diagnosis of asthma. C1 [Tse, Sze Man; Gold, Diane R.; Sordillo, Joanne E.; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Weiss, Scott T.; Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Tse, Sze Man; Gold, Diane R.; Sordillo, Joanne E.; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Weiss, Scott T.; Litonjua, Augusto A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Tse, Sze Man] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulm Med, Boston, MA 02114 USA. [Hoffman, Elaine B.] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gillman, MatthewW.; Rifas-Shiman, Sheryl L.] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Cambridge, MA 02138 USA. RP Tse, SM (reprint author), Channing Labs, 181 Long Wood Ave, Boston, MA 02115 USA. EM reszt@channing.harvard.edu OI Litonjua, Augusto/0000-0003-0422-5875 FU National Heart, Lung, and Blood Institute [NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, 16052]; General Clinical Research Center from the National Center for Research Resources [M01RR00051, M01RR0099718-24, M01RR02719-14, RR00036]; National Institutes of Health [P50 HL67664, U01 HL65899, T32 HL07427]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases/R01 grant [AI035786]; National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute (NHLBI); NHLBI; Agency for Healthcare Research and Quality; NIH; [R01 HL064925]; [R01 HD034568] FX The Childhood Asthma Management Program is supported by contracts NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 with the National Heart, Lung, and Blood Institute and General Clinical Research Center grants M01RR00051, M01RR0099718-24, M01RR02719-14, and RR00036 from the National Center for Research Resources. Additional support for this research came from grants P50 HL67664, U01 HL65899, and T32 HL07427 from the National Institutes of Health and the National Heart, Lung, and Blood Institute. Home Allergens is funded by National Institute of Allergy and Infectious Diseases/R01 grant AI035786. Project Viva is funded by R01 HL064925 and R01 HD034568.; S. M. Tse, M. W. Gillman, and K. G. Tantisira have been supported by/have received one or more grants from or have one or more grants pending with the National Institutes of Health (NIH). D. R. Gold has been supported by one or more grants from the National Institute of Allergy and Infectious Diseases. A. L. Fuhlbrigge has been supported by one or more grants from and has received support for travel from the National Heart, Lung, and Blood Institute (NHLBI); is a Board member for Merck; has consultancy arrangements with Merck, GlaxoSmithKline, ICON Medical Imaging, Sunovion, the Lovelace Respiratory Research Institute, and Dmagi; and has received one or more grants from or has one or more grants pending with the NHLBI and the Agency for Healthcare Research and Quality. A. A. Litonjua has been supported by one or more grants from the NIH and has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. NR 32 TC 13 Z9 13 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2013 VL 132 IS 3 BP 554 EP + DI 10.1016/j.jaci.2013.03.031 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 207OS UT WOS:000323612000005 PM 23683464 ER PT J AU Quintiliani, LM Whiteley, JA Johnson, EJ Viswanath, K AF Quintiliani, Lisa M. Whiteley, Jessica A. Johnson, Elizabeth J. Viswanath, K. TI Time Availability and Preference for e-Health Communication Channels for Nutrition and Physical Activity SO JOURNAL OF CANCER EDUCATION LA English DT Article DE e-health; Time availability; Non-traditional college students; Nutrition; Physical activity ID INTERVENTIONS AB The aim of this study was to examine the relationship between time availability and preference for computer-based (e-health) communication channels when receiving nutrition and physical activity information, two key behaviors related to cancer prevention. Students from a large, diverse, urban university (n = 397) completed a web-based survey indicating their usage patterns and preferences for multiple eHealth channels. Bivariate analyses were performed based on a measure of time availability, comprised of working status (25 h/week or more, 1-24 h/week, or not working) and enrollment status (full-time or part-time). Most e-health channels were broadly used by students and did not differ according to time availability. Those with the most amount of time available preferred receiving nutrition and physical activity information via social networking more frequently compared to those with the least amount of time available (60 versus 43 %, P a parts per thousand currency signaEuro parts per thousand 0.05). Our study suggests that time availability may be another important factor to consider when planning cancer prevention programs. C1 [Quintiliani, Lisa M.] Boston Univ, Crosstown Ctr, MISU, Boston, MA 02118 USA. [Whiteley, Jessica A.] Univ Massachusetts, Boston, MA 02125 USA. [Johnson, Elizabeth J.] Commonwealth Psychol Associates, Boston, MA 02110 USA. [Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Quintiliani, LM (reprint author), Boston Univ, Crosstown Ctr, MISU, 801 Massachusetts Ave,2nd Floor, Boston, MA 02118 USA. EM lisa.quintiliani@bmc.org OI Quintiliani, Lisa/0000-0002-3328-6768 FU National Cancer Institute; UMass Boston/Dana-Farber-Harvard Cancer Center U56 Partnership [5 U56 CA118641, 5 R03 CA139943, 5 R25 CA057711] FX This work was conducted with the support of grants from the National Cancer Institute (Pre-Pilot Grant from the UMass Boston/Dana-Farber-Harvard Cancer Center U56 Partnership 5 U56 CA118641; grant 5 R03 CA139943; and Training Grant 5 R25 CA057711). The funding sources did not have a role in the study design, data interpretation, or manuscript publishing. NR 11 TC 0 Z9 0 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SEP PY 2013 VL 28 IS 3 BP 408 EP 411 DI 10.1007/s13187-013-0477-x PG 4 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 206JN UT WOS:000323516400004 PM 23653371 ER PT J AU Liapakis, IE Englander, M Vrentzos, NP Derdas, SP Paschalis, EI AF Liapakis, Ioannis E. Englander, Miriam Vrentzos, Nikolaos P. Derdas, Stavros P. Paschalis, Eleftherios I. TI Secondary rhinoplasty fixations with hyaluronic acid SO JOURNAL OF COSMETIC DERMATOLOGY LA English DT Article DE rhinoplasty; nose irregularities; hyaluronic acid; swelling ID CUTANEOUS GRANULOMATOUS REACTION; CALCIUM HYDROXYLAPATITE; NASAL AUGMENTATION; SOFT-TISSUE; GEL; FILLER; ASYMMETRIES; INJECTION AB The management of nasal deformities especially after rhinoplasty is a challenge. Postsurgical edema may last 6-8months, causing aesthetic irregularities and nose deformities. The aim of this study is to present the correction of minor nose deformities secondary to rhinoplasty using hyaluronic acid subdermal injections. Eleven patients were treated between 2009 and 2011 with subdermal injections of hyaluronic acid (24mg/mL) with 0.3% lidocaine (Juvederm, Allergan, Pringy-France) at the 1-month follow-up visit. The volume of hyaluronic acid injected varied from 0.4 to 1mL according to the deformity. Injections were aimed to correct minor surface irregularities and to provide aesthetic symmetry. These patients were followed for at least 12months postoperatively. Irregularities were aesthetically corrected immediately after hyaluronic acid injections. No complications were reported with the exception of minor swelling that resolved within 1week. Esthetic correction was achieved in all patients as determined by the surgeon as well as by overall patient's satisfaction. Our 1-year follow-up data suggest that hyaluronic acid absorption is slow enough to provide the necessary time for postsurgical edema resorption. Rhinoplasty is among the most commonly used procedures for aesthetic improvement in men and women. However, achievement of the final outcome may take several months due to the induced postsurgical edema. Subdermal hyaluronic acid injections can provide temporary correction of these nose irregularities. Our data suggest that subdermal hyaluronic acid injections may provide immediate and long-lasting correction of these minor deformities. As a result, the aesthetic outcome is achieved and maintained throughout the postsurgical course of edema decompression. C1 [Liapakis, Ioannis E.; Vrentzos, Nikolaos P.] OpsisClinical, Plast & Reconstruct Surg, Iraklion, Greece. [Englander, Miriam] Cleveland Clin, Dept Ophthalmol, Cole Eye Inst, Cleveland, OH 44106 USA. [Derdas, Stavros P.] Univ Crete, Sch Med, Lab Clin Virol, Iraklion, Greece. [Paschalis, Eleftherios I.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Paschalis, EI (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM eleftherios_paschalis@meei.harvard.edu NR 17 TC 3 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1473-2130 J9 J COSMET DERMATOL-US JI J. Cosmet. Dermatol. PD SEP PY 2013 VL 12 IS 3 BP 235 EP 239 DI 10.1111/jocd.12046 PG 5 WC Dermatology SC Dermatology GA 209AT UT WOS:000323726200010 PM 23992166 ER PT J AU Gubbels, CS Welt, CK Dumoulin, JCM Robben, SGF Gordon, CM Dunselman, GAJ Rubio-Gozalbo, ME Berry, GT AF Gubbels, Cynthia S. Welt, Corrine K. Dumoulin, John C. M. Robben, Simon G. F. Gordon, Catherine M. Dunselman, Gerard A. J. Rubio-Gozalbo, M. Estela Berry, Gerard T. TI The male reproductive system in classic galactosemia: cryptorchidism and low semen volume SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID HYPERGONADOTROPIC HYPOGONADISM; MEN; PHENOTYPE; RELAXIN; INHIBIN; SEX AB Previous studies examining reproductive parameters in men with galactosemia have inconsistently demonstrated abnormalities. We hypothesized that men with galactosemia may demonstrate evidence of reproductive dysfunction. Pubertal history, physical examination, hormone levels and semen analyses were examined in 26 males with galactosemia and compared to those in 46 controls. The prevalence of cryptorchidism was higher in men with galactosemia than in the general population [11.6 % vs. 1.0 % (95%CI: 0.75-1.26; p < 0.001)]. Testosterone (461 +/- 125 vs. 532 +/- 133 ng%; p = 0.04), inhibin B (144 +/- 66 vs. 183 +/- 52 pg/mL; p = 0.002) and sperm concentration (46 +/- 36 vs. 112 +/- 75 x 10(6) spermatozoa/mL; p = 0.01) were lower and SHBG was higher (40.7 +/- 21.5 vs 26.7 +/- 14.6; p = 0.002) in men with galactosemia compared to controls. Semen volume was below normal in seven out of 12 men with galactosemia. Men with galactosemia have a higher than expected prevalence of cryptorchidism and low semen volumes. The subtle decrease in testosterone and inhibin B levels and sperm count may indicate mild defects in Sertoli and Leydig cell function, but does not point towards severe infertility causing reproductive impairment. Follow-up studies are needed to further determine the clinical consequences of these abnormalities. C1 [Gubbels, Cynthia S.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6202 AZ Maastricht, Netherlands. [Welt, Corrine K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA USA. [Dumoulin, John C. M.; Dunselman, Gerard A. J.] Maastricht Univ, Med Ctr, Dept Obstet & Gynaecol, NL-6202 AZ Maastricht, Netherlands. [Dumoulin, John C. M.] Maastricht Univ, Med Ctr, Ctr Reprod Med, NL-6202 AZ Maastricht, Netherlands. [Robben, Simon G. F.] Maastricht Univ, Med Ctr, Dept Radiol, NL-6202 AZ Maastricht, Netherlands. [Gordon, Catherine M.] Hasbro Childrens Hosp, Div Endocrinol, Providence, RI USA. [Gordon, Catherine M.] Hasbro Childrens Hosp, Div Adolescent Med, Providence, RI USA. [Gordon, Catherine M.] Brown Univ, Providence, RI 02912 USA. [Gordon, Catherine M.] Childrens Hosp, Boston, MA 02115 USA. [Gordon, Catherine M.] Harvard Univ, Sch Med, Boston, MA USA. [Dunselman, Gerard A. J.] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, NL-6202 AZ Maastricht, Netherlands. [Rubio-Gozalbo, M. Estela] Maastricht Univ, Med Ctr, Dept Pediat & Lab Genet Metab Dis, NL-6202 AZ Maastricht, Netherlands. [Berry, Gerard T.] Harvard Univ, Sch Med, Manton Ctr Orphan Dis Res, Div Genet,Childrens Hosp Boston, Boston, MA USA. RP Gubbels, CS (reprint author), Maastricht Univ, Med Ctr, Dept Clin Genet, Postbus 5800, NL-6202 AZ Maastricht, Netherlands. EM c.gubbels@mumc.nl RI rubio, estela/H-1833-2011; OI Berry, Gerard/0000-0001-5299-3313; Welt, Corrine/0000-0002-8219-5504 FU Dutch Galactosemia Association (GVN); Parents of Galactosemic Children Association (PGCA); Clinical Translational Study Unit (CTSU) at Children's Hospital Boston FX These studies were supported by the Dutch Galactosemia Association (GVN), Parents of Galactosemic Children Association (PGCA) and the Clinical Translational Study Unit (CTSU) at Children's Hospital Boston. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsor NR 31 TC 6 Z9 8 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD SEP PY 2013 VL 36 IS 5 BP 779 EP 786 DI 10.1007/s10545-012-9539-1 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 208FK UT WOS:000323662500008 PM 23053469 ER PT J AU Vranceanu, AM Shaefer, JR Saadi, AF Slawsby, E Sarin, J Scult, M Benson, H Denninger, JW AF Vranceanu, Ana-Maria Shaefer, Jeffery R. Saadi, Ashkan Fahandej Slawsby, Ellen Sarin, Jaya Scult, Matthew Benson, Herbert Denninger, John W. TI The Relaxation Response Resiliency Enhancement Program in the Management of Chronic Refractory Temporomandibular Joint Disorder: Results from a Pilot Study SO JOURNAL OF MUSCULOSKELETAL PAIN LA English DT Article DE Pain; relaxation response resiliency enhancement program; TMD ID MEDICAL OUTCOMES; HEALTH SURVEY; BIOFEEDBACK; PAIN; INTERVENTION; DYSFUNCTION; FRAMEWORK; EFFICACY; STRESS AB Objectives: This is an open-pilot study to evaluate the feasibility, acceptability and efficacy of a pain-specific version of an established mind-body medicine program, the Relaxation Response [RR] Resiliency Program [R3P], in patients with chronic temporomandibular disorder [TMD]. Methods: Male and female with at least a six-month history of pain involving the masticatory muscles were sought in the Orofacial Pain Centers of the Massachusetts General Hospital [MGH] or through an advertisement sent to MGH employees from 2008 to 2010. Eligible participants underwent the R3P intervention [eight group sessions] after standard medical management. Pre- and post-group patients underwent objective measures of impairment [vertical and lateral range of motion with and without pain, temporomandibular joint and muscle pain palpation, and algometer measures] and completed psychosocial measures [Symptom Severity Index, Perceived Stress Scale, the Symptom Checklist-90-Revised and Short Form 36 Health Survey]. Results: Twenty-four subjects [16 females, 90% from MGH Orofacial Pain Centers, 10% from among MGH employees], mean age 38 years, met eligibility criteria and participated in the study. The intervention was highly feasible and accepted by patients, as evidenced by a 92% rate of completion. Paired t-test analyses revealed improvement on self-reported pain measures: pain intensity [p<0.02], pain frequency [p<0.002], pain duration [p<0.027], pain tolerability [p<0.009] and on several objective tests. Conclusions: The pain specific R3P is efficacious in reducing objective and subjective symptoms in patients with chronic refractory TMD. The comprehensive intervention, which combines educational information about pain with RR, cognitive behavioral and resiliency-enhancement skills, is accepted by patients and may be more efficacious than other treatments with fewer elements. C1 [Vranceanu, Ana-Maria; Shaefer, Jeffery R.; Saadi, Ashkan Fahandej; Slawsby, Ellen; Sarin, Jaya; Scult, Matthew; Benson, Herbert; Denninger, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Vranceanu, AM (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq, Boston, MA 02114 USA. EM avranceanu@partners.org FU Center for Disease Control and Prevention [R01DP000339] FX This research was funded by the Center for Disease Control and Prevention [Grant R01DP000339]. NR 24 TC 4 Z9 4 U1 1 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1058-2452 J9 J MUSCULOSKELET PAIN JI J. Musculoskelet. Pain PD SEP PY 2013 VL 21 IS 3 BP 224 EP 230 DI 10.3109/10582452.2013.827289 PG 7 WC Rehabilitation; Rheumatology SC Rehabilitation; Rheumatology GA 206NF UT WOS:000323527900005 PM 26568669 ER PT J AU Muldoon, MF Erickson, KI Goodpaster, BH Jakicic, JM Conklin, SM Sekikawa, A Yao, JK Manuck, SB AF Muldoon, Matthew F. Erickson, Kirk I. Goodpaster, Bret H. Jakicic, John M. Conklin, Sarah M. Sekikawa, Akira Yao, Jeffrey K. Manuck, Stephen B. TI Concurrent Physical Activity Modifies the Association between n3 Long-Chain Fatty Acids and Cardiometabolic Risk in Mid life Adults SO JOURNAL OF NUTRITION LA English DT Article ID EXERCISE-INDUCED ALTERATIONS; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; FISH-OIL; METABOLIC SYNDROME; WEIGHT-LOSS; YOUNG-ADULTS; N-3; FITNESS; GLUCOSE AB Greater consumption of n3 (omega 3) polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce risk for cardiovascular disease events, yet their effects on metabolic risk factors and diabetes remain unclear. This cross-sectional study used a community volunteer sample to test whether the associations between n3 fatty acids and cardiometabolic risk vary as a function of physical activity. Participants were 344 generally healthy adults, 30-54 y of age, not taking fish oil supplements or confounding medications. Serum phospholipid EPA and DHA were used together (EPA+DHA) as a biomarker of n3 fatty acid exposure. Cardiometabolic risk was calculated as a continuous measure based on standardized distributions of blood pressure, waist circumference, HDL cholesterol, triglycerides, glucose, and a simple count of risk factors. Insulin resistance was estimated from the homeostatic model assessment. Physical activity was found to predict cardiometabolic risk (P <= 0.02) and insulin resistance (P <= 0.02) and to moderate the association between EPA+DHA and both cardiometabolic risk (P-interaction <= 0.02) and insulin resistance (P-interaction <= 0.02). Specifically, higher EPA+DHA was associated with lower cardiometabolic risk and insulin resistance in persons engaged in regular physical activity but not in relatively inactive individuals. These findings were noted in several components of cardiometabolic risk, in men and women separately, and in models adjusted for overall diet quality. In midlife adults, habitual physical activity may be necessary to unmask the salutary effects of n3 fatty acids on cardiometabolic risk and insulin resistance. C1 [Muldoon, Matthew F.] Univ Pittsburgh, Sch Med, Heart & Vasc Inst, Pittsburgh, PA 15213 USA. [Erickson, Kirk I.; Manuck, Stephen B.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Jakicic, John M.] Univ Pittsburgh, Sch Educ, Dept Hlth & Phys Act, Pittsburgh, PA 15260 USA. [Conklin, Sarah M.] Allegheny Coll, Dept Psychol & Neurosci, Meadville, PA 16335 USA. [Sekikawa, Akira] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Muldoon, MF (reprint author), Univ Pittsburgh, Sch Med, Heart & Vasc Inst, Pittsburgh, PA 15213 USA. EM mfm10@pitt.edu OI Sekikawa, Akira/0000-0002-7197-6321 FU U.S. Public Health Service Awards [P01 HL40962, R21 HL081282] FX Supported by U.S. Public Health Service Awards P01 HL40962 and R21 HL081282. NR 40 TC 2 Z9 2 U1 1 U2 22 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2013 VL 143 IS 9 BP 1414 EP 1420 DI 10.3945/jn.113.174078 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 205SX UT WOS:000323466200008 PM 23884386 ER PT J AU Jacques, PF Cassidy, A Rogers, G Peterson, JJ Meigs, JB Dwyer, JT AF Jacques, Paul F. Cassidy, Aedin Rogers, Gail Peterson, Julia J. Meigs, James B. Dwyer, Johanna T. TI Higher Dietary Flavonol Intake Is Associated with Lower Incidence of Type 2 Diabetes SO JOURNAL OF NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; CARDIOVASCULAR-DISEASE; INCREASING PREVALENCE; POSTMENOPAUSAL WOMEN; AMELIORATES HYPERGLYCEMIA; INSULIN SENSITIVITY; OXIDATIVE STRESS; MEAT CONSUMPTION; RISK-FACTORS; HEALTH AB Substantial experimental evidence suggests that several flavonoid classes are involved in glucose metabolism, but few clinical or epidemiologic studies exist that provide supporting human evidence for this relationship. The objective of this study was to determine if habitual intakes of specific flavonoid classes are related to incidence of type 2 diabetes (T2D). We followed 2915 members of the Framingham Offspring cohort who were free of T2D at baseline from 1991 to 2008. Diabetes was defined by either elevated fasting glucose (>= 7.0 mmol/L) or initiation of hypoglycemic medication during follow-up. Dietary intakes of 6 flavonoid classes and total flavonoids were assessed using a validated, semiquantitative food frequency questionnaire. We observed 308 incident cases of T2D during a mean follow-up period of 11.9 y (range 2.5-16.8 y). After multivariable adjusted, time-dependent analyses, which accounted for long-term flavonoid intake during follow-up, each 2.5-fold increase in flavonol intake was associated with a 26% lower incidence of T2D [HR = 0.74(95% Cl: 0.61, 0.90); P-trend = 0.003] and each 2.5-fold increase in flavan-3-ol intake was marginally associated with an 11% lower incidence of T2D [HR =. 0.89 (95% Cl: 0.80, 1.00); P-trend = 0.06]. No other associations between flavonoid classes and risk of T2D were observed. Our observations support previous experimental evidence of a possible beneficial relationship between increased flavonol intake and risk of T2D. C1 [Jacques, Paul F.; Rogers, Gail; Dwyer, Johanna T.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Jacques, Paul F.; Peterson, Julia J.; Dwyer, Johanna T.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Cassidy, Aedin] Univ E Anglia, Norwich Med Sch, Dept Nutr, Norwich NR4 7TJ, Norfolk, England. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. EM paul.jacques@tufts.edu OI Dwyer, Johanna/0000-0002-0783-1769 FU North American Branch of the International Life Sciences Institute; National Heart Lung and Blood Institute [N01-HC-25195]; National Institute of Diabetes, Digestive and Kidney Diseases [K24 DK080140]; Biotechnology and Biological Sciences Research Council, UK; USDA Agricultural Research Service [58-1950-0-014] FX Supported by grants from the North American Branch of the International Life Sciences Institute, the National Heart Lung and Blood Institute (contract N01-HC-25195), the National Institute of Diabetes, Digestive and Kidney Diseases (K24 DK080140), the Biotechnology and Biological Sciences Research Council, UK, and the USDA Agricultural Research Service (agreement 58-1950-0-014). This is a free access article, distributed under terms (http://www.nutrition.org/publications/guidelines-and-policies/license/) that permit unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. NR 54 TC 29 Z9 30 U1 1 U2 23 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD SEP PY 2013 VL 143 IS 9 BP 1474 EP 1480 DI 10.3945/jn.113.177212 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 205SX UT WOS:000323466200016 PM 23902957 ER EF