FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fryer, SL Woods, SW Kiehl, KA Calhoun, VD Pearlson, GD Roach, BJ Ford, JM McGlashan, TH Mathalon, DH AF Fryer, Susanna L. Woods, Scott W. Kiehl, Kent A. Calhoun, Vince D. Pearlson, Godfrey D. Roach, Brian J. Ford, Judith M. McGlashan, Thomas H. Mathalon, Daniel H. TI Youth at Clinical High-Risk for Psychosis Fail to Suppress Default Mode Regions During Task Performance SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE psychosis prodrome; ultra high-risk; schizophrenia; default mode network; working memory C1 [Fryer, Susanna L.; Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fryer, Susanna L.; Roach, Brian J.; Ford, Judith M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Woods, Scott W.; Calhoun, Vince D.; Pearlson, Godfrey D.; Ford, Judith M.; McGlashan, Thomas H.; Mathalon, Daniel H.] Yale Univ, New Haven, CT USA. [Kiehl, Kent A.; Calhoun, Vince D.] Univ New Mexico, Albuquerque, NM 87131 USA. [Kiehl, Kent A.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Pearlson, Godfrey D.] Olin Neuropsychiat Res Ctr, Inst Living, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 2 U2 7 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 MAY 1 PY 2013 VL 73 IS 9 SU S MA 941 BP 301S EP 301S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801249 ER PT J AU Storage, S Mandelkern, M Phuong, J Kozman, M Brody, A AF Storage, Steven Mandelkern, Mark Phuong, Jonathan Kozman, Maggie Brody, Arthur TI Relationship Between Harm Avoidance and Nicotinic Acetylcholine Receptor Density SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2013 CL San Francisco, CA SP Soc Biol Psychiat DE Tobacco Dependence; Harm Avoidance; Positron Emission Tomography; Nicotinic Acetylcholine Receptor; Temperament and Character Inventory C1 [Storage, Steven] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Mandelkern, Mark] VA Greater Los Angeles Healthcare Syst, Nucl Med, Los Angeles, CA USA. [Phuong, Jonathan; Kozman, Maggie] VA Greater Los Angeles Healthcare Syst, Res, Los Angeles, CA USA. [Brody, Arthur] Univ Calif Los Angeles, Los Angeles, CA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2013 VL 73 IS 9 SU S MA 964 BP 308S EP 308S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 140RE UT WOS:000318671801272 ER PT J AU Bao, Y Giovannucci, EL Kraft, P Qian, ZR Wu, C Ogino, S Gaziano, JM Stampfer, MJ Ma, J Buring, JE Sesso, HD Lee, IM Rifai, N Pollak, MN Jiao, L Lessin, L Cochrane, BB Manson, JE Fuchs, CS Wolpin, BM AF Bao, Ying Giovannucci, Edward L. Kraft, Peter Qian, Zhi Rong Wu, Chen Ogino, Shuji Gaziano, J. Michael Stampfer, Meir J. Ma, Jing Buring, Julie E. Sesso, Howard D. Lee, I-Min Rifai, Nader Pollak, Michael N. Jiao, Li Lessin, Lawrence Cochrane, Barbara B. Manson, JoAnn E. Fuchs, Charles S. Wolpin, Brian M. TI Inflammatory Plasma Markers and Pancreatic Cancer Risk: A Prospective Study of Five U.S. Cohorts SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; CARDIOVASCULAR-DISEASE; WOMENS HEALTH; INSULIN-RESISTANCE; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; SERUM-LEVELS; OBESITY; MEN AB Chronic inflammation may play a role in the development of pancreatic cancer. However, few prospective studies have examined the association between plasma inflammatory markers and pancreatic cancer risk. Therefore, we investigated the association of prediagnostic circulating C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-alpha receptor II (TNF-alpha R2) with subsequent pancreatic cancer risk in a prospective, nested case-control study of 470 cases and 1,094 controls from Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. The median follow-up time of cases was 7.2 years (range 1-26 years). No association was observed between plasma CRP, IL-6, and TNF-alpha R2 and the risk of pancreatic cancer. Comparing extreme quintiles, the multivariate ORs were 1.10 [95% confidence interval (CI), 0.74-1.63; P-trend = 0.81] for CRP, 1.19 (95% CI, 0.81-1.76; P-trend = 0.08) for IL-6, and 0.88 (95% CI, 0.58-1.33; P-trend = 0.57) for TNF-alpha R2. In conclusion, prediagnostic levels of circulating CRP, IL-6, and TNF-alpha R2 were not associated with the risk of pancreatic cancer, suggesting that systemic inflammation as measured by circulating inflammatory factors is unlikely to play a major role in the development of pancreatic cancer. (C) 2013 AACR. C1 [Bao, Ying; Giovannucci, Edward L.; Stampfer, Meir J.; Ma, Jing; Manson, JoAnn E.; Fuchs, Charles S.; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Gaziano, J. Michael; Buring, Julie E.; Sesso, Howard D.; Lee, I-Min; Manson, JoAnn E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Buring, Julie E.] Dept Ambulatory Care & Prevent, Boston, MA USA. [Kraft, Peter; Buring, Julie E.; Sesso, Howard D.; Lee, I-Min] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Giovannucci, Edward L.; Kraft, Peter; Wu, Chen; Ogino, Shuji; Stampfer, Meir J.; Ma, Jing; Buring, Julie E.; Sesso, Howard D.; Lee, I-Min; Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Rifai, Nader] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Qian, Zhi Rong; Ogino, Shuji; Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pollak, Michael N.] McGill Univ, Fac Med, Dept Oncol, Canc Prevent Res Unit, Montreal, PQ, Canada. [Jiao, Li] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Cochrane, Barbara B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. W Virginia Univ, Dept Community Med, Morgantown, WV 26506 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Washington, DC USA. [Lessin, Lawrence] Medstar Res Inst, Washington, DC USA. RP Bao, Y (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ying.bao@channing.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120 FU National Cancer Institute, NIH [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908]; NCI [K07 CA140790]; American Society of Clinical Oncology; Howard Hughes Medical Institute; Lustgarten Foundation; NIH (Bethesda, MD) [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; NIH [CA047988, HL043851, HL080467] FX The NHS and HPFS are supported by the National Cancer Institute, NIH (Grant no. P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908). B. Wolpin is supported by NCI K07 CA140790, an American Society of Clinical Oncology Career Development Award, a Howard Hughes Medical Institute Early Career Physician-Scientist Award, and the Lustgarten Foundation.; The PHS I is supported by grant nos. CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595 from the NIH (Bethesda, MD).; The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.; The WHS is supported by grants CA047988, HL043851, and HL080467 from the NIH. NR 46 TC 11 Z9 11 U1 0 U2 4 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 MAY PY 2013 VL 22 IS 5 BP 855 EP 861 DI 10.1158/1055-9965.EPI-12-1458 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 143UR UT WOS:000318894200013 PM 23462920 ER PT J AU Houssami, N Abraham, LA Kerlikowske, K Buist, DSM Irwig, L Lee, J Miglioretti, DL AF Houssami, Nehmat Abraham, Linn A. Kerlikowske, Karla Buist, Diana S. M. Irwig, Les Lee, Janie Miglioretti, Diana L. TI Risk Factors for Second Screen-Detected or Interval Breast Cancers in Women with a Personal History of Breast Cancer Participating in Mammography Screening SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PREDICTION MODEL; FOLLOW-UP; SURVEILLANCE; SURVIVORS; DENSITY; CONSERVATION; VALIDATION; GUIDELINES; ACCURACY; OBESITY AB Background: Women with a personal history of breast cancer (PHBC) have increased risk of an interval cancer. We aimed to identify risk factors for second (ipsilateral or contralateral) screen-detected or interval breast cancer within 1 year of screening in PHBC women. Methods: Screening mammograms from women with history of early-stage breast cancer at Breast Cancer Surveillance Consortium-affiliated facilities (1996-2008) were examined. Associations between woman-level, screen-level, and first cancer variables and the probability of a second breast cancer were modeled using multinomial logistic regression for three outcomes [screen-detected invasive breast cancer, interval invasive breast cancer, or ductal carcinoma in situ (DCIS)] relative to no second breast cancer. Results: There were 697 second breast cancers, of these 240 were interval cancers, among 67,819 screens in 20,941 women. In separate models for women with DCIS or invasive first cancer, first breast cancer surgery predicted all three second breast cancer outcomes (P < 0.001), and high ORs for second breast cancers (between 1.95 and 4.82) were estimated for breast conservation without radiation (relative to mastectomy). In women with invasive first breast cancer, additional variables predicted risk (P<0.05) for at least one of the three outcomes: first-degree family history, dense breasts, longer time between mammograms, young age at first breast cancer, first breast cancer stage, and adjuvant systemic therapy for first breast cancer; and risk of interval invasive breast cancer was highest in women < 40 years at first breast cancer (OR, 3.41; 1.34-8.70), those with extremely dense breasts (OR, 2.55; 1.4-4.67), and those treated with breast conservation without radiation (OR, 2.67; 1.53-4.65). Conclusion: Although the risk of a second breast cancer is modest, our models identify risk factors for interval second breast cancer in PHBC women. Impact: Our findings may guide discussion and evaluations of tailored breast screening in PHBC women, and incorporating this information into clinical decision-making warrants further research. (C) 2013 AACR. C1 [Houssami, Nehmat; Irwig, Les] Univ Sydney, Screening & Test Evaluat Program, Sch Publ Hlth, Sydney Med Sch, Sydney, NSW 2006, Australia. [Abraham, Linn A.; Buist, Diana S. M.; Miglioretti, Diana L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. [Lee, Janie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Lee, Janie] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lee, Janie] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Miglioretti, Diana L.] Univ Calif Davis, Div Biostat, Dept Publ Hlth Sci, Davis, CA USA. RP Houssami, N (reprint author), Univ Sydney, Screening & Test Evaluat Program, Sch Publ Hlth A27, Sydney Med Sch, Sydney, NSW 2006, Australia. EM nehmath@med.usyd.edu.au FU National Breast Cancer Foundation (NBCF); National Health and Medical Research Council (NHMRC) [633003]; National Cancer Institute [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040, HHSN261201100031C] FX N. Houssami receives research support through a National Breast Cancer Foundation (NBCF) Practitioner Fellowship. L. Irwig and N. Houssami are partly supported via National Health and Medical Research Council (NHMRC) program grant 633003 to the Screening & Test Evaluation Program. This work was supported by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040, HHSN261201100031C). NR 30 TC 12 Z9 13 U1 0 U2 13 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 MAY PY 2013 VL 22 IS 5 BP 946 EP 961 DI 10.1158/1055-9965.EPI-12-1208-T PG 16 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 143UR UT WOS:000318894200023 PM 23513042 ER PT J AU Lo, WK Chan, WW AF Lo, Wai-Kit Chan, Walter W. TI Proton Pump Inhibitor Use and the Risk of Small Intestinal Bacterial Overgrowth: A Meta-analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review DE Hypochlorhydria; Drug; Small Bowel Flora; Reflux; Side Effect ID IRRITABLE-BOWEL-SYNDROME; GASTRIC-ACID-SECRETION; ELDERLY PATIENTS; OMEPRAZOLE; PREDICTORS; THERAPY; DISEASE; HYPOCHLORHYDRIA; SUPPRESSION; SIBO AB BACKGROUND & AIMS: Use of proton pump inhibitors (PPIs) could predispose individuals to small intestinal bacterial overgrowth (SIBO) by altering the intraluminal environment and bacterial flora. There is controversy regarding the risk of SIBO among PPI users because of conflicting results from prior studies. A systematic review and meta-analysis were performed to evaluate the association between PPI use and SIBO, using objective clinical outcome measures. METHODS: Clinical studies comparing SIBO risk among adult users of PPIs vs nonusers were identified in MEDLINE/PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the National Institutes of Health Clinical Trials databases through July 2012. Two reviewers independently extracted data on study characteristics and outcomes. The primary metameter was the odds ratio (OR) of SIBO among PPI users vs nonusers. Subgroup analyses were performed to examine the influence of study characteristics, such as SIBO diagnostic modality, on study outcome. RESULTS: Eleven studies (n = 3134) met inclusion criteria. The pooled OR of SIBO in PPI users vs nonusers was 2.282 (95% confidence interval [CI], 1.238 - 4.205). No significant single large study or temporal effect was seen. Subgroup analysis revealed an association between SIBO and PPI use in studies that used duodenal or jejunal aspirate cultures to diagnose SIBO (OR, 7.587; 95% CI, 1.805-31.894), but no relationship was found between SIBO and PPI use in studies that used the glucose hydrogen breath test (OR, 1.93; 95% CI, 0.69-5.42). Funnel plot analysis identified 4 outlying studies, indicating the possible presence of publication bias. CONCLUSIONS: PPI use statistically was associated with SIBO risk, but only when the diagnosis was made by a highly accurate test (duodenal or jejunal aspirate culture). Differences in study results could arise from the use of different tests to diagnose SIBO. C1 [Lo, Wai-Kit; Chan, Walter W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. Boston VA Healthcare Syst, Dept Gastroenterol, Boston, MA USA. RP Chan, WW (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM wwchan@partners.org OI Lo, Wai-Kit/0000-0002-1526-352X NR 43 TC 46 Z9 50 U1 2 U2 16 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 MAY PY 2013 VL 11 IS 5 BP 483 EP 490 DI 10.1016/j.cgh.2012.12.011 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 140UX UT WOS:000318682600011 PM 23270866 ER PT J AU Sonnenberg, A Lee, BY AF Sonnenberg, Amnon Lee, Brent Y. TI Birth-Cohort Analysis of Colorectal Cancer Incidence in the United States SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter ID MORTALITY; TRENDS; ULCER C1 [Sonnenberg, Amnon; Lee, Brent Y.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 4 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2013 VL 11 IS 5 BP 582 EP 583 DI 10.1016/j.cgh.2013.01.022 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 140UX UT WOS:000318682600030 PM 23376795 ER PT J AU Adamia, S Pilarski, PM Belch, AR Pilarski, LM AF Adamia, Sophia Pilarski, Patrick M. Belch, Andrew R. Pilarski, Linda M. TI Aberrant Splicing, Hyaluronan Synthases and Intracellular Hyaluronan as Drivers of Oncogenesis and Potential Drug Targets SO CURRENT CANCER DRUG TARGETS LA English DT Article DE Alternative splicing; drug targets; hyaluronan; hyaluronan synthases; oncogenesis ID CHRONIC LYMPHOCYTIC-LEUKEMIA; GENOME-WIDE ASSOCIATION; COLON-CARCINOMA CELLS; LARGE B-CELL; MARROW ENDOTHELIAL-CELLS; ACUTE MYELOID-LEUKEMIA; MULTIPLE-MYELOMA; BREAST-CANCER; SOMATIC HYPERMUTATION; PROSTATE-CANCER AB Current evidence suggests a significant role of aberrant splicing in the development and maintenance of malignancy. This multistep, tightly regulated epigenetic process leads to the production of abnormal proteins with abnormal functions contributing to underlying mechanisms of malignant transformation. Splicing patterns in malignant cells can be altered not only by the mutations detected on the aberrantly spliced gene, but also by the mutations detected on the genes encoding splicing factors. For example, aberrant pre-mRNA splicing, leading to intracellular or extracellular HA synthesis by HASs, contributes to the initiation and progression of various types of cancer. The influence of intracellular HA appears to be particularly significant and is promoted by aberrant splicing. In this review we report a model describing oncogenic potential of aberrant splicing, with a focus on HAS1 and intracellular HA. We also suggest that the influence of splicing mutations on malignant disease is likely multifactorial. For the triple axis of HA, HAS1 and RHAMM, mutations in HAS1 provide an indicator that these aberrations contribute to the events that lead to malignancy through increased risk and predisposition. Here, we also summarize the impact of splicing abnormalities on cancer and the possible oncogenic impact of aberrantly spliced HAS1. In conclusion, we emphasize that specific gene splice variants and the splicing process itself offer potential targets for novel drug treatment strategies. C1 [Adamia, Sophia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pilarski, Patrick M.] Univ Alberta, Dept Comp Sci, Edmonton, AB, Canada. [Belch, Andrew R.; Pilarski, Linda M.] Univ Alberta, Dept Oncol, Edmonton, AB, Canada. [Belch, Andrew R.; Pilarski, Linda M.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. RP Adamia, S (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM Sophia_Adamia@dfci.harvard.edu RI Xia, Bo/P-9380-2016 FU Alberta Cancer Foundation; Myeloma Alberta; Alberta Innovates Centre for Machine Learning; Alberta Innovates - Technology Futures; ASH scholar award; LLS (Leukemia & Lymphoma Society) FX SA is supported by an ASH scholar award for Clinical/Translational Research Fellows, and LLS (Leukemia & Lymphoma Society) Translational Research Program grant. PMP is funded by the Alberta Innovates Centre for Machine Learning, and from Alberta Innovates - Technology Futures. LMP and ARB are funded by the Alberta Cancer Foundation and Myeloma Alberta. NR 151 TC 12 Z9 12 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 MAY PY 2013 VL 13 IS 4 BP 347 EP 361 PG 15 WC Oncology SC Oncology GA 144XV UT WOS:000318976500001 PM 23517594 ER PT J AU Calkins, AW Berman, NC Wilhelm, S AF Calkins, Amanda W. Berman, Noah C. Wilhelm, Sabine TI Recent Advances in Research on Cognition and Emotion in OCD: A Review SO CURRENT PSYCHIATRY REPORTS LA English DT Review DE Obsessive-compulsive Disorder; OCD; Cognition; Emotion; Cognitive Processes; Cognitive Model; Anxiety; Disgust sensitivity; Psychiatry ID OBSESSIVE-COMPULSIVE DISORDER; ANXIETY SENSITIVITY INDEX-3; UCS-EXPECTANCY BIAS; SYMPTOM DIMENSIONS; RESPONSIBILITY BELIEFS; NONCLINICAL SAMPLE; DISGUST; UNCERTAINTY; INTOLERANCE; CONTAMINATION AB The cognitive model of OCD suggests that misinterpreting intrusive thoughts as unacceptable leads to increased anxiety and attempts to suppress or ignore the thoughts through avoidance or compulsive rituals. An insidious negative feedback loop develops as one's attention focuses on these thoughts and in turn the unwanted thoughts do not respond to efforts to avoid or suppress. This article is a current review of the research on cognitive processes in obsessive-compulsive disorder (OCD). We review research that has (1) empirically validated the theoretical underpinnings of the cognitive model, (2) altered maladaptive cognitive processes through state-of-the-art experimental procedures, (3) refined our understanding of the relationship between obsessive beliefs and OC symptoms and (4) examined how underlying traits (e.g., anxiety and disgust sensitivity) relate to the development and maintenance of OCD. We discuss the clinical implications of this research. C1 [Calkins, Amanda W.; Berman, Noah C.; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Calkins, AW (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM acalkins@partners.org OI Baker, Amanda/0000-0002-0103-5411 FU National Institutes of Health, National Institute of Mental Health; International OCD Foundation; Tourette Syndrome Association; Charlie Waller Institute; University of Reading; Internationale Tagung in Prien am Chiemsee; North Shore University Hospital; Long Island Jewish Medical Center; Massachusetts General Hospital Psychiatry Academy; Guilford Press; Oxford University Press; New Harbinger Publications; Association for Behavioral and Cognitive Therapies; National Institutes of Health FX S. Wilhelm has received grants and research support from the National Institutes of Health, National Institute of Mental Health and International OCD Foundation; has received payment for lectures including service on speakers bureaus from the Tourette Syndrome Association, Charlie Waller Institute, University of Reading, International OCD Foundation, Internationale Tagung in Prien am Chiemsee, North Shore University Hospital and Long Island Jewish Medical Center, and Massachusetts General Hospital Psychiatry Academy; has received payment for manuscript preparation from Guilford Press; has received royalties from Oxford University Press, New Harbinger Publications and Guilford Press; has received payment for serving on editorial boards from the Association for Behavioral and Cognitive Therapies; and has received payment for grant reviews from National Institutes of Health. NR 56 TC 9 Z9 9 U1 4 U2 68 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD MAY PY 2013 VL 15 IS 5 AR 357 DI 10.1007/s11920-013-0357-4 PG 7 WC Psychiatry SC Psychiatry GA 141YD UT WOS:000318761600004 PM 23529510 ER PT J AU Friedlander, AH Chang, TI Aghazadehsanai, N Berenji, GR Harada, ND Garrett, NR AF Friedlander, A. H. Chang, T. I. Aghazadehsanai, N. Berenji, G. R. Harada, N. D. Garrett, N. R. TI Panoramic images of white and black post-menopausal females evidencing carotid calcifications are at high risk of comorbid osteopenia of the femoral neck SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article DE atherosclerosis; panoramic images; osteopenia; fractures ID BONE-MINERAL DENSITY; SERVICES TASK-FORCE; ARTERY CALCIFICATIONS; HIP FRACTURE; OLDER WOMEN; OSTEOPOROSIS; RADIOGRAPHY; POPULATION; MORTALITY; ATHEROMA AB Objectives: Femoral neck fractures in older females resulting from decreased bone mineral density (BMD; osteopenia) are associated with increased morbidity and mortality. Bone mineralization inhibition is probably controlled by proteins which also foster vascular calcification. Therefore, we evaluated the relationship between calcified carotid artery plaque (CCAP) on panoramic images and BMD on dual energy X-ray absorptiometry (DXA) bone scans. Methods: Images and hospital records identified by dentists defined two study groups (20 white females and 24 black females) having CCAP and an incidentally obtained bone scan. Ethnically matched (age +/- 7 years, body mass index +/- 3 units) control groups with panoramic images devoid of CCAP and accompanying DXA scan were likewise constituted. A physician determined the BMD on the DXA. Results: Females with CCAP had significantly (p = 0.03) poorer BMD at the femoral neck than those without CCAP. Although mean femoral neck BMD was significantly lower (p = 0.009) for white than for black females, there was no significant interaction between race and CCAP (p = 0.80). Conclusion: We observed a significant inverse association between the CCAP on panoramic images and femoral neck BMD in post-menopausal white females. C1 [Friedlander, A. H.; Chang, T. I.; Berenji, G. R.] Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA USA. [Friedlander, A. H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. [Friedlander, A. H.; Chang, T. I.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Aghazadehsanai, N.] Vet Affairs Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Sect, Dent Serv, Los Angeles, CA USA. [Berenji, G. R.; Harada, N. D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Harada, N. D.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Garrett, N. R.] Univ Calif Los Angeles, Sch Dent, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov FU Research Facilities Improvement Program from the National Center for Research Resources, National Institutes of Health [C06 RR-14529-01] FX Elements of this investigation were conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR-14529-01 from the National Center for Research Resources, National Institutes of Health. NR 31 TC 5 Z9 6 U1 0 U2 5 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD MAY PY 2013 VL 42 IS 5 AR 20120195 DI 10.1259/dmfr.20120195 PG 6 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA 146NY UT WOS:000319099000001 PM 23571481 ER PT J AU Soria, JC Baselga, J Hanna, N Laurie, SA Bahleda, R Felip, E Calvo, E Armand, JP Shepherd, FA Harbison, CT Berman, D Park, JS Zhang, S Vakkalagadda, B Kurland, JF Pathak, AK Herbst, RS AF Soria, Jean-Charles Baselga, Jose Hanna, Nasser Laurie, Scott A. Bahleda, Rastislav Felip, Enriqueta Calvo, Emiliano Armand, Jean-Pierre Shepherd, Frances A. Harbison, Christopher T. Berman, David Park, Jong-Soon Zhang, Steven Vakkalagadda, Blisse Kurland, John F. Pathak, Ashutosh K. Herbst, Roy S. TI Phase I-IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Phase I-II; Pan-HER/VEGFR inhibitor; Solid tumours ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; ADVANCED BREAST-CANCER; NUDE-MOUSE MODEL; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; PLUS IRINOTECAN; DOUBLE-BLIND; ANGIOGENESIS; CARCINOMA AB Purpose: BMS-690514 is a potent, reversible oral inhibitor of epidermal growth factor receptor (EGFR/HER-1), HER-2 and -4, and vascular endothelial growth factor receptors (VEGFRs)-1 to -3 offering targeted inhibition of tumour growth and vascularisation in a single agent. This phase I-IIa study was designed to identify the maximum tolerated dose (MTD) and assess safety, antitumour activity, pharmacokinetics and pharmacodynamics of BMS-690514. Patients and methods: In phase I, patients with advanced solid tumours received escalating doses of once-daily BMS-690514. In phase IIa, erlotinib-naive (cohort A) or erlotinib-resistant (cohort B) patients with advanced non-small-cell lung cancer (NSCLC) received BMS-690514 once-daily at the MTD. Results: In phase I (n = 28), the MTD was determined to be 200 mg daily. BMS-690514 was rapidly absorbed and highly metabolised after repeated oral administration with minimum drug accumulation. In phase IIa (n = 62), the most frequent treatment-related adverse events were diarrhoea and acneiform rash. Adverse events that led to >1 discontinuation were diarrhoea (n = 4; 4%) and rash (n = 2; 2%). Disease control (>= 4 months) and objective response rates, respectively, were 43.3% and 3.3% (cohort A) and 22.6% and 3.2% (cohort B). Six of 21 (29%) NSCLC patients with wild-type EGFR achieved disease control versus seven of 10 (70%) patients with EGFR mutations (including T790M). At MTD, BMS-690514 modulated pharmacodynamic biomarkers associated with inhibition of VEGFR-and EGFR-signalling pathways. Conclusion: This phase I-IIa study suggests that BMS-690514 has manageable safety profile and antitumour activity in patients with NSCLC at 200 mg/d, including those with EGFR mutations conferring resistance to erlotinib. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Soria, Jean-Charles; Bahleda, Rastislav] South Paris Univ, Inst Gustave Roussy, SITEP, Villejuif, France. [Baselga, Jose; Felip, Enriqueta] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hanna, Nasser] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Laurie, Scott A.] Ottawa Hosp, Ctr Canc, Ottawa, ON, Canada. [Calvo, Emiliano] START Madrid, Ctr Integral Oncol Clara Campal, Madrid, Spain. [Armand, Jean-Pierre] Inst Claudius Regaud, Toulouse, France. [Shepherd, Frances A.] Univ Toronto, Div Med Oncol, Toronto, ON, Canada. [Harbison, Christopher T.; Berman, David; Park, Jong-Soon; Zhang, Steven; Vakkalagadda, Blisse; Kurland, John F.; Pathak, Ashutosh K.] Bristol Myers Squibb Co, Princeton, NJ USA. [Herbst, Roy S.] Smilow Canc Hosp, Yale Comprehens Canc Ctr, New Haven, CT USA. RP Soria, JC (reprint author), Inst Gustave Roussy, Villejuif, France. EM soria@igr.fr FU Bristol-Myers Squibb [CA187-002]; AstraZeneca; Eli Lilly FX Supported by research funding from Bristol-Myers Squibb (Study No. CA187-002).; J.-C. Soria has received honoraria from Bristol-Myers Squibb. J. Baselga has no conflicts of interest to disclose. N. Hanna has received research funding from AstraZeneca and Eli Lilly. S. A. Laurie has no conflicts of interest to disclose. R. Bahleda has no conflicts of interest to disclose. E. Felip has no conflicts of interest to disclose. E. Calvo has no conflicts of interest to disclose. J.-P. Armand has no conflicts of interest to disclose. F. A. Shepherd has a consultant or advisory relationship with and has received honoraria from Daiichi Sankyo, Inc., Roche, and Bristol-Myers Squibb. C. T. Harbison has an employment position at and stock or ownership interests in Bristol-Myers Squibb. D. Berman has an employment position at and stock or ownership interests in Bristol-Myers Squibb. J.-S. Park has an employment position at Bristol-Myers Squibb. S. Zhang has an employment position at and stock or ownership interests in Bristol-Myers Squibb. B. Vakkalagadda has an employment position at and stock or ownership interests in Bristol-Myers Squibb. J. F. Kurland has an employment position at Bristol-Myers Squibb. A. K. Pathak has an employment position at and stock or ownership interests in Bristol-Myers Squibb. R. S. Herbst has no conflicts of interest to disclose. NR 42 TC 9 Z9 9 U1 0 U2 12 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 MAY PY 2013 VL 49 IS 8 BP 1815 EP 1824 DI 10.1016/j.ejca.2013.02.012 PG 10 WC Oncology SC Oncology GA 139UN UT WOS:000318610500003 PM 23490650 ER PT J AU Gukovsky, I Li, N Todoric, J Gukovskaya, A Karin, M AF Gukovsky, Ilya Li, Ning Todoric, Jelena Gukovskaya, Anna Karin, Michael TI Inflammation, Autophagy, and Obesity: Common Features in the Pathogenesis of Pancreatitis and Pancreatic Cancer SO GASTROENTEROLOGY LA English DT Review DE Pancreatic Acinar Cell; Cytokines; Neutrophil; Pancreatic Ductal Adenocarcinoma; K-Ras ID NF-KAPPA-B; CERULEIN-INDUCED PANCREATITIS; TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; ACINAR-CELLS; INSULIN-RESISTANCE; DEFICIENT MICE; TRYPSINOGEN ACTIVATION; DUCTAL ADENOCARCINOMA; SIGNALING PATHWAYS AB Inflammation and autophagy are cellular defense mechanisms. When these processes are deregulated (deficient or overactivated) they produce pathologic effects, such as oxidative stress, metabolic impairments, and cell death. Unresolved inflammation and disrupted regulation of autophagy are common features of pancreatitis and pancreatic cancer. Furthermore, obesity, a risk factor for pancreatitis and pancreatic cancer, promotes inflammation and inhibits or deregulates autophagy, creating an environment that facilitates the induction and progression of pancreatic diseases. However, little is known about how inflammation, autophagy, and obesity interact to promote exocrine pancreatic disorders. We review the roles of inflammation and autophagy, and their deregulation by obesity, in pancreatic diseases. We discuss the connections among disordered pathways and important areas for future research. C1 [Gukovsky, Ilya; Gukovskaya, Anna] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gukovsky, Ilya; Gukovskaya, Anna] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Li, Ning; Todoric, Jelena; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Li, Ning; Todoric, Jelena; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pathol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Todoric, Jelena] Med Univ Vienna, Dept Lab Med, Vienna, Austria. RP Gukovskaya, A (reprint author), Univ Calif Los Angeles, Dept Vet Affairs, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU Department of Veterans Affairs; National Institutes of Health [DK59936]; Pancreatic Cancer Research Lustgarten Foundation grant [RFP-B-007]; Erwin Schrodinger Fellowship of the Austrian Science Fund [J 3233]; [P01 CA163200]; [AA19730]; [AI043477]; [CA163798]; [P50 AA011999]; [R03CA167120] FX Our research was supported by the Department of Veterans Affairs and National Institutes of Health grants DK59936, and, in part, P01 CA163200 (A.G.), AA19730 (I.G.), AI043477 (M.K.), CA163798 (M.K.), P50 AA011999 (A.G, I.G, Pilot Project to M.K.), and R03CA167120 (N.L.), by a Pancreatic Cancer Research Lustgarten Foundation grant RFP-B-007 (M.K.), and the Erwin Schrodinger Fellowship J 3233 of the Austrian Science Fund (J.T.). NR 201 TC 73 Z9 77 U1 5 U2 51 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 MAY PY 2013 VL 144 IS 6 BP 1199 EP + DI 10.1053/j.gastro.2013.02.007 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144AE UT WOS:000318910600006 PM 23622129 ER PT J AU Farrell, JJ Fernandez-del Castillo, C AF Farrell, James J. Fernandez-del Castillo, Carlos TI Pancreatic Cystic Neoplasms: Management and Unanswered Questions SO GASTROENTEROLOGY LA English DT Review DE IPMN; Cyst Fluid; Surveillance, EUS ID PAPILLARY-MUCINOUS NEOPLASMS; TERM-FOLLOW-UP; INTERNATIONAL CONSENSUS GUIDELINES; SOLID-PSEUDOPAPILLARY TUMORS; OVARIAN-TYPE STROMA; SEROUS-CYSTADENOMA; DUCTAL ADENOCARCINOMAS; ENDOSCOPIC ULTRASOUND; ENDOCRINE NEOPLASMS; NATURAL-HISTORY AB Approximately 10% of persons 70 years old or older are now diagnosed with pancreatic cysts, but it is not clear which ones require additional analysis, interventions, or follow-up. Primary care doctors rely on gastroenterologists for direction because no one wants to miss a diagnosis of pancreatic cancer, but meanwhile there is pressure to limit use of diagnostic tests and limit costs. We review the different cystic neoplasms of the pancreas and diagnostic strategies based on clinical features and imaging data. We discuss surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines. Intraductal papillary mucinous neoplasm (particularly the branch duct variant) is the lesion most frequently identified incidentally. We report what is known about its pathology, its risk of developing into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk. We also review surgical treatment and strategies for surveillance of pancreatic cysts. C1 [Farrell, James J.] Yale Univ, Sch Med, Yale Pancreas Ctr, New Haven, CT 06510 USA. [Farrell, James J.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pancreas & Biliary Surg Program, Boston, MA USA. RP Farrell, JJ (reprint author), Yale Univ, Sch Med, Sect Digest Dis, LMP 1080,15 York St, New Haven, CT 06510 USA. EM j.farrell@yale.edu NR 100 TC 61 Z9 64 U1 0 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2013 VL 144 IS 6 BP 1303 EP 1315 DI 10.1053/j.gastro.2013.01.073 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 144AE UT WOS:000318910600017 PM 23622140 ER PT J AU Dobscha, SK Corson, K Helmer, DA Bair, MJ Denneson, LM Brandt, C Beane, A Ganzini, L AF Dobscha, Steven K. Corson, Kathryn Helmer, Drew A. Bair, Matthew J. Denneson, Lauren M. Brandt, Cynthia Beane, Anna Ganzini, Linda TI Brief assessment for suicidal ideation in OEF/OIF veterans with positive depression screens SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Depression; Screening; Suicide; Veterans ID PRIMARY-CARE; RISK; PHYSICIAN; SEVERITY; VALIDITY; RACE; IRAQ AB Objectives: We describe processes, rates, and patient and system correlates of brief structured assessments (BSAs) for suicidal ideation among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with positive depression screens. Methods: Electronic Veterans Affairs (VA) medical record and Department of Defense data were used to identify individual-level and BSA-process variables for 1662 OEF/OIF veterans at three VA Medical Centers. Results: Overall, 1349/1662 (81%) veterans received BSAs for suicidal ideation within 1 month of depression screening; 94% of BSAs were conducted within 1 day. Stratified analyses revealed significant intersite differences in veteran demographics, instruments used, clinical setting and staff performing assessments, and correlates of assessment completion. At two sites, men were more likely to be assessed than women [odds ratio (OR)=2.15 (95% confidence interval {CI}=1.06-4.38) and 3.14 (CI=1.27-7.76)]. In a combined model adjusted for intrasite correlation, assessment was less likely during months 8-12 and 13-18 of the study period [OR=0.39 (CI=0.28-0.54) and OR=0.48 (95% CI=0.35-0.68), respectively] and more likely to occur among veterans receiving depression or posttraumatic stress disorder diagnoses on the day of depression screening [OR=1.83 (CI=1.36-2.46) and OR=1.50 (CI=1.13-1.98), respectively]. Conclusions: Most veterans with positive depression screens receive timely BSAs for suicidal ideation. Processes used for brief assessment for suicidal ideation vary substantially across VA settings. Published by Elsevier Inc. C1 [Dobscha, Steven K.; Corson, Kathryn; Denneson, Lauren M.; Beane, Anna; Ganzini, Linda] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Phys & Mental D, Portland, OR USA. [Dobscha, Steven K.; Corson, Kathryn; Denneson, Lauren M.; Ganzini, Linda] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Helmer, Drew A.] VA New Jersey Hlth Care Syst, War Related Illness & Injury Study Ctr, E Orange, NJ USA. [Helmer, Drew A.] Baylor Coll Med, Houston, TX 77030 USA. [Bair, Matthew J.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA. [Brandt, Cynthia] West Haven Vet Affairs Med Ctr, West Haven, CT USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, POB 1034 P3MHADM, Portland, OR 97207 USA. EM steven.dobscha@va.gov FU Department of Veterans Affairs, Veterans Health Administration; Health Services Research and Development Service Project [DHI-08-096] FX We gratefully acknowledge Jonathon Duckart, M. P. S.; Kathryn Dickinson, M. P. H.; Ashley McComb, B. S.; Jose Perez, B. S.; and Megan Crutchfield, M. P. H., for assistance with collecting and organizing data and reviewing medical records. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service Project DHI-08-096. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 33 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2013 VL 35 IS 3 BP 272 EP 278 DI 10.1016/j.genhosppsych.2012.12.001 PG 7 WC Psychiatry SC Psychiatry GA 145DZ UT WOS:000318995800010 PM 23351524 ER PT J AU Hall, TO Wan, JY Mata, IF Kerr, KF Snapinn, KW Samii, A Roberts, JW Agarwal, P Zabetian, CP Edwards, KL AF Hall, Taryn O. Wan, Jia Y. Mata, Ignacio F. Kerr, Kathleen F. Snapinn, Katherine W. Samii, Ali Roberts, John W. Agarwal, Pinky Zabetian, Cyrus P. Edwards, Karen L. TI Risk prediction for complex diseases: application to Parkinson disease SO GENETICS IN MEDICINE LA English DT Article DE genetics; Parkinson disease; risk prediction ID GENOME-WIDE ASSOCIATION; VPS35 MUTATIONS; CANCER RISK; IDENTIFICATION; POLYMORPHISMS; SPECIFICITY; SENSITIVITY; LIMITATIONS; POPULATION; VARIANTS AB Purpose: The aim of this study was to evaluate the risk of Parkinson disease using clinical and demographic data alone and when combined with information from genes associated with Parkinson disease. Methods: A total of 1,967 participants in the dbGAP NeuroGenetics Research Consortium data set were included. Single-nucleotide polymorphisms associated with Parkinson disease at a genome-wide significance level in previous genome-wide association studies were included in risk prediction. Risk allele scores were calculated as the weighted count of the minor alleles. Five models were constructed. Discriminatory capability was evaluated using the area under the curve. Results: Both family history and genetic risk scores increased risk for Parkinson disease. Although the fullest model, which included both family history and genetic risk information, resulted in the highest area under the curve, there were no significant differences between models using family history alone and those using genetic information alone. Conclusion: Adding genome-wide association study-derived genotypes, family history information, or both to standard demographic risk factors for Parkinson disease resulted in an improvement in discriminatory capacity. In the full model, the contributions of genotype data and family history information to discriminatory capacity were similar, and both were statistically significant. This suggests that there is limited overlap between genetic risk factors identified through genome-wide association study and unmeasured susceptibility variants captured by family history. Our results are similar to those of studies of other complex diseases and indicate that genetic risk prediction for Parkinson disease requires identification of additional genetic risk factors and/or better methods for risk prediction in order to achieve a degree of risk prediction that is clinically useful. C1 [Hall, Taryn O.; Edwards, Karen L.] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA. [Wan, Jia Y.; Snapinn, Katherine W.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mata, Ignacio F.; Samii, Ali; Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Mata, Ignacio F.; Samii, Ali; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Kerr, Kathleen F.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Agarwal, Pinky] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. RP Edwards, KL (reprint author), Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA. EM keddy@uw.edu RI Kerr, Kathleen/A-2893-2013; OI Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian, Cyrus/0000-0002-7739-4306 FU Department of Veterans Affairs [1I01BX000531]; National Institutes of Health [P50 NS062684, R01 NS065070, R01 NS036960] FX This work was supported by funding from the Department of Veterans Affairs (1I01BX000531) and the National Institutes of Health (P50 NS062684, R01 NS065070, R01 NS036960). NR 34 TC 7 Z9 7 U1 1 U2 4 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 MAY PY 2013 VL 15 IS 5 BP 361 EP 367 DI 10.1038/gim.2012.109 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 143SN UT WOS:000318888600007 PM 23222663 ER PT J AU Golnabi, AH Meaney, PM Paulsen, KD AF Golnabi, Amir H. Meaney, Paul M. Paulsen, Keith D. TI Tomographic Microwave Imaging With Incorporated Prior Spatial Information SO IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES LA English DT Article DE A priori spatial information; image reconstruction; microwave imaging; multimodality imaging; regularization; soft prior; tissue dielectric properties ID BREAST-CANCER; RECONSTRUCTION; TISSUES; SYSTEM; DIAGNOSIS; WOMEN AB We have implemented a soft prior regularization technique for microwave tomographic imaging that exploits spatial prior information from alternative imaging modalities. We have previously demonstrated in both simulation and phantom experiments that this approach is capable of improved property recovery compared with our conventional Tikhonov regularized method. An important concern with this type of integration is that the spatial information could be implemented in such a way as to overly influence or even bias the final results. For this reason, we have performed a rigorous quantitative analysis of this approach using both simulation and phantom experiments to investigate the sensitivity to inaccurate or even false spatial information. The majority of cases tested here involved simple targets to easily assess problems when the prior shapes are incorrect with respect to size and location or even when there is an extra target that does not exist in the actual imaging situation. In addition, we have also performed a simulated experiment utilizing anthropomorphic breast structural information to explore the capabilities in more challenging situations. The results are encouraging and demonstrate that the soft prior regularization can be a powerful tool, especially where the goal is specificity instead of sensitivity. C1 [Golnabi, Amir H.; Meaney, Paul M.; Paulsen, Keith D.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Golnabi, AH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Golnabi.Amir@MGH.Harvard.edu; Paul.M.Meaney@Dart-mouth.edu; Keith.D.Paulsen@Dartmouth.edu FU National Institutes of Health (NIH); National Cancer Institute (NCI) [R33-CA102938-04] FX Manuscript received October 15, 2012; revised January 28, 2013; accepted January 30, 2013. Date of publication March 07, 2013; date of current version May 02, 2013. This work was supported in part by the National Institutes of Health (NIH) and the National Cancer Institute (NCI) under Grant R33-CA102938-04. NR 28 TC 17 Z9 17 U1 0 U2 13 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9480 J9 IEEE T MICROW THEORY JI IEEE Trans. Microw. Theory Tech. PD MAY PY 2013 VL 61 IS 5 SI SI BP 2129 EP 2136 DI 10.1109/TMTT.2013.2247413 PN 2 PG 8 WC Engineering, Electrical & Electronic SC Engineering GA 141BT UT WOS:000318701100017 ER PT J AU Osguthorpe, JD AF Osguthorpe, John David TI Pathophysiology of and potential new therapies for allergic rhinitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Review DE T-helper lymphocyte; IgE; eosinophil; mast cell; humanized monoclonal antibody; cytokine; chemokine ID HYGIENE HYPOTHESIS; NASAL POLYPOSIS; IMMUNOTHERAPY; INFLAMMATION; DISEASE; ASTHMA; IGE; RHINOSINUSITIS; MECHANISMS; DISORDERS AB Background Advancement in laboratory techniques in the past decade, coupled with clinical studies, has afforded a better understanding of the genetic and molecular mechanisms underlying allergy. Methods The literature on the pathophysiology of allergic rhinitis, systemic and local, was reviewed, with emphasis on the last 3 years. Results The basis in allergic rhinitis for the T-lymphocyte helper 2 cell and associated cytokine bias, and the ameliorating effects of T-regulatory lymphocytes and their cytokines, is summarized. New or currently under development pharmacotherapeutic agents are briefly presented. Conclusion Much of the molecular basis for the manifestations of allergy can now be explained, and may afford strategies to interrupt the development of disease or ameliorate such already present. C1 [Osguthorpe, John David] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. RP Osguthorpe, JD (reprint author), Ralph Johnson VA Med Ctr, Surg Serv 112, 109 Bee St, Charleston, SC 29401 USA. EM osguthjd@musc.edu NR 57 TC 7 Z9 8 U1 2 U2 11 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 MAY PY 2013 VL 3 IS 5 BP 384 EP 392 DI 10.1002/alr.21120 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 146ET UT WOS:000319073200008 PM 23193028 ER PT J AU Cardarella, S Johnson, BE AF Cardarella, Stephanie Johnson, Bruce E. TI Meta-Analysis of EGFR Kinase Inhibitors: Not Always Greater Than the Sum of Its Parts SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CELL LUNG-CANCER; PHASE-III TRIAL; 1ST-LINE TREATMENT; CARBOPLATIN-PACLITAXEL; OPEN-LABEL; GEFITINIB; CHEMOTHERAPY; ADENOCARCINOMA; MUTATIONS; ERLOTINIB C1 [Cardarella, Stephanie; Johnson, Bruce E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Cardarella, Stephanie; Johnson, Bruce E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cardarella, Stephanie; Johnson, Bruce E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,Dana 1234, Boston, MA 02215 USA. EM bejohnson@partners.org NR 19 TC 2 Z9 2 U1 0 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 MAY PY 2013 VL 105 IS 9 BP 589 EP 590 DI 10.1093/jnci/djt085 PG 2 WC Oncology SC Oncology GA 140UK UT WOS:000318681200003 PM 23594425 ER PT J AU Brooks, GA Li, L Sharma, DB Weeks, JC Hassett, MJ Yabroff, KR Schrag, D AF Brooks, Gabriel A. Li, Ling Sharma, Dhruv B. Weeks, Jane C. Hassett, Michael J. Yabroff, K. Robin Schrag, Deborah TI Regional Variation in Spending and Survival for Older Adults With Advanced Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OF-LIFE TREATMENT; CELL LUNG-CANCER; PALLIATIVE CARE; COMORBIDITY INDEX; COSTS; END; INTENSITY; OUTCOMES; SATISFACTION; PREFERENCES AB Background Medicare spending varies substantially across the United States. We evaluated the association between mean regional spending and survival in advanced cancer. Methods We identified 116 523 subjects with advanced cancer from 2002 to 2007, using Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Subjects were aged 65 years and older with non-small cell lung, colon, breast, prostate, or pancreas cancer. Of these subjects, 61 083 had incident advanced-stage cancer (incident cohort) and 98 935 had death from cancer (decedent cohort); 37% of subjects were included in both cohorts. Subjects were linked to one of 80 hospital referral regions within SEER areas. We estimated mean regional spending in both cohorts. We assessed the primary outcome, survival, in the incident cohort; the exposure measure was the quintile of regional spending in the decedent cohort. Survival in quintiles 2 through 5 was compared with that in quintile 1 (lowest spending quintile) using Cox regression models. Results From quintile 1 to 5, mean regional spending increased by 32% and 41% in the incident and decedent cohorts (incident cohort: $28 854 to $37 971; decedent cohort: $27 446 to $38 630). The association between spending and survival varied by cancer site and quintile; hazard ratios ranged from 0.92 (95% confidence interval [CI] = 0.82 to 1.04, pancreas cancer quintile 5) to 1.24 (95% CI = 1.11 to 1.39, breast cancer quintile 3). In most cases, differences in survival between quintile 1 and quintiles 2 through 5 were not statistically significant. Conclusion There is substantial regional variation in Medicare spending for advanced cancer, yet no consistent association between mean regional spending and survival. C1 [Brooks, Gabriel A.; Li, Ling; Sharma, Dhruv B.; Weeks, Jane C.; Hassett, Michael J.; Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Brooks, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gabrooks@partners.org OI Brooks, Gabriel/0000-0003-3984-9995; Yabroff, K. Robin/0000-0003-0644-5572 FU National Cancer Institute of the National Institutes of Health [5R01CA131847, T32CA009172] FX This work was supported by grants from the National Cancer Institute of the National Institutes of Health (5R01CA131847 to DS, and T32CA009172, an institutional training grant supporting GAB). 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 39 TC 33 Z9 33 U1 5 U2 13 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 MAY PY 2013 VL 105 IS 9 BP 634 EP 642 DI 10.1093/jnci/djt025 PG 9 WC Oncology SC Oncology GA 140UK UT WOS:000318681200010 PM 23482657 ER PT J AU Badr, CE Van Hoppe, S Dumbuya, H Tjon-Kon-Fat, LA Tannous, BA AF Badr, Christian E. Van Hoppe, Stephanie Dumbuya, Hawasatu Tjon-Kon-Fat, Lee-Ann Tannous, Bakhos A. TI Targeting Cancer Cells With the Natural Compound Obtusaquinone SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OXIDATIVE STRESS; TUMOR-SUPPRESSOR; STEM-CELLS; P53; GLIOBLASTOMA; ROS; CARCINOMA; SURVIVAL AB Background Tumor cells present high levels of oxidative stress. Cancer therapeutics exploiting such biochemical changes by increasing reactive oxygen species (ROS) production or decreasing intracellular ROS scavengers could provide a powerful treatment strategy. Methods To test the effect of our compound, obtusaquinone (OBT), we used several cell viability assays on seven different glioblastoma (GBM) cell lines and primary cells and on 12 different cell lines representing various cancer types in culture as well as on subcutaneous (n = 7 mice per group) and two intracranial GBM (n = 6-8 mice per group) and breast cancer (n = 6 mice per group) tumor models in vivo. Immunoblotting, immunostaining, flow cytometry, and biochemical assays were used to investigate the OBT mechanism of action. Histopathological analysis (n = 2 mice per group) and blood chemistry (n = 2 mice per group) were used to test for any compound-related toxicity. Statistical tests were two-sided. Results OBT induced rapid increase in intracellular ROS levels, downregulation of cellular glutathione levels and increase in its oxidized form, and activation of cellular stress pathways and DNA damage, subsequently leading to apoptosis. Oxidative stress is believed to be the main mechanism through which this compounds targets cancer cells. OBT was well tolerated in mice, slowed tumor growth, and statistically prolonged survival in GBM tumor models. The ratio of median survival in U251 intracranial model in OBT vs control was 1.367 (95% confidence interval [CI] of ratio = 1.031 to 1.367, P=.008). Tumor growth inhibition was also observed in a mouse breast cancer model (average tumor volume per mouse, OBT vs control: 36.3 vs 200.4 mm(3), difference = 164.1 mm(3), 95% CI = 72.6 to 255.6 mm(3), P =.005). Conclusions Given its properties and efficacy in cancer killing, our results suggest that OBT is a promising cancer therapeutic. C1 [Badr, Christian E.; Van Hoppe, Stephanie; Dumbuya, Hawasatu; Tjon-Kon-Fat, Lee-Ann; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Neurosci Ctr, Boston, MA 02114 USA. [Badr, Christian E.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM badr.christian@mgh.harvard.edu; btannous@hms.harvard.edu FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [1R21NS061051, P30NS045776, 1R01NS064983]; American Brain Tumor Association FX This work was supported by grants from National Institutes of Health/National Institute of Neurological Disorders and Stroke (1R21NS061051, P30NS045776, and 1R01NS064983 [to BAT]) and the American Brain Tumor Association (to CEB). NR 25 TC 9 Z9 9 U1 0 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 MAY PY 2013 VL 105 IS 9 BP 643 EP 653 DI 10.1093/jnci/djt037 PG 11 WC Oncology SC Oncology GA 140UK UT WOS:000318681200011 PM 23479453 ER PT J AU Hanna, SC Krishnan, B Bailey, ST Moschos, SJ Kuan, PF Shimamura, T Osborne, LD Siegel, MB Duncan, LM O'Brien, ET Superfine, R Miller, CR Simon, MC Wong, KK Kim, WY AF Hanna, Sara C. Krishnan, Bhavani Bailey, Sean T. Moschos, Stergios J. Kuan, Pei-Fen Shimamura, Takeshi Osborne, Lukas D. Siegel, Marni B. Duncan, Lyn M. O'Brien, E. Tim, III Superfine, Richard Miller, C. Ryan Simon, M. Celeste Wong, Kwok-Kin Kim, William Y. TI HIF1 alpha and HIF2 alpha independently activate SRC to promote melanoma metastases SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; GROWTH-FACTOR EXPRESSION; TUMOR PROGRESSION; IN-VIVO; CANCER; HIF-2-ALPHA; HIF-1-ALPHA; TARGET; CELLS; MITF AB Malignant melanoma is characterized by a propensity for early lymphatic and hematogenous spread. The hypoxia-inducible factor (HIP) family of transcription factors is upregulated in melanoma by key oncogenic drivers. HIFs promote the activation of genes involved in cancer initiation, progression, and metastases. Hypoxia has been shown to enhance the invasiveness and metastatic potential of tumor cells by regulating the genes involved in the breakdown of the ECM as well as genes that control motility and adhesion of tumor cells. Using a Pten-deficient, Brarmutant genetically engineered mouse model of melanoma, we demonstrated that inactivation of HIF1 alpha or HIF2 alpha abrogates metastasis without affecting primary tumor formation. HIF1 alpha and HIF2 alpha drive melanoma invasion and invadopodia formation through PDGFR alpha and focal adhesion kinase-mediated (FAK-mediated) activation of SRC and by coordinating ECM degradation via MT1-MMP and MMP2 expression. These results establish the importance of HIFs in melanoma progression and demonstrate that HIF1 alpha and HIF2 alpha activate independent transcriptional programs that promote metastasis by coordinately regulating cell invasion and ECM remodeling. C1 [Hanna, Sara C.; Krishnan, Bhavani; Bailey, Sean T.; Moschos, Stergios J.; Kuan, Pei-Fen; Siegel, Marni B.; Miller, C. Ryan; Kim, William Y.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Kuan, Pei-Fen] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Shimamura, Takeshi] Loyola Univ Chicago, Dept Mol Pharmacol & Therapeut, Oncol Inst, Maywood, IL USA. [Osborne, Lukas D.; O'Brien, E. Tim, III; Superfine, Richard] Univ N Carolina, Dept Phys & Astron, Chapel Hill, NC 27599 USA. [Duncan, Lyn M.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. [Miller, C. Ryan] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Simon, M. Celeste] Univ Penn, Howard Hughes Med Inst, Dept Cell & Dev Biol, Abramson Family Canc Res Inst,Dept Canc Biol, Philadelphia, PA 19104 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Dept Med Oncol, Boston, MA USA. [Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Lowe Ctr Thorac Oncol, Boston, MA USA. [Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. RP Kim, WY (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295, Chapel Hill, NC 27599 USA. EM wykim@med.unc.edu RI Miller, Ryan/B-9365-2008; OI Miller, Ryan/0000-0002-0096-8762; wong, kwok kin/0000-0001-6323-235X FU CGIBD Imaging and Histology Core [NIH P30-DK-034987]; National Cancer Institute [3P30CA016086]; National Institute of Environmental Health Sciences [3P30ES010126]; Department of Defense [W81XWH-09-2-0042, PC094631, W81XWH-08-1-0064]; UNC University Cancer Research Fund (UCRF); Specialized Program of Research Excellence [IP50CA93683-03]; Melanoma Research Foundation, NIH [R01 CA142794, R33 CA155618, U54 CA151652]; NCI [CA 122794, 166480, 163896, 140594, 141576, 120964, 154303]; University Cancer Research Fund (UCRF) FX We would like to acknowledge the members of the Kim and Sharpless labs as well as Nicole Neel and Kim Monahan for useful discussions and advice. We thank Carolyn Suitt of the University of North Carolina CGIBD Histology Core Facility, which is supported by the CGIBD Imaging and Histology Core (NIH P30-DK-034987). The authors thank the UNC TPL, which is supported, in part, by grants from the National Cancer Institute (3P30CA016086), the National Institute of Environmental Health Sciences (3P30ES010126), the Department of Defense (W81XWH-09-2-0042), and the UNC University Cancer Research Fund (UCRF). We would also like to thank the UNC Microscopy Services Laboratory Director, Robert Bagnell and the UNC Mouse Phase 1 Unit (MP1U). The SkinSPORE melanocytic tumor progression array was developed with the support of the Specialized Program of Research Excellence (IP50CA93683-03). This work was supported by the Melanoma Research Foundation (to W.Y. Kim), NIH R01 CA142794 (to W.Y. Kim), R33 CA155618 (to R. Superfine), U54 CA151652 (to W.Y. Kim and R. Superfine), NCI CA 122794, 166480, 163896, 140594, 141576, 120964, and 154303 (to K. K. Wong), the University Cancer Research Fund (UCRF), and Department of Defense grants PC094631 and W81XWH-08-1-0064 (to W.Y. Kim). W.Y. Kim is a Damon Runyon Merck Clinical Investigator. NR 41 TC 51 Z9 53 U1 0 U2 14 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 MAY PY 2013 VL 123 IS 5 BP 2078 EP 2093 DI 10.1172/JCI66715 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 145OA UT WOS:000319025100029 PM 23563312 ER PT J AU Thurman, JM Kulik, L Orth, H Wong, M Renner, B Sargsyan, SA Mitchell, LM Hourcade, DE Hannan, JP Kovacs, JM Coughlin, B Woodell, AS Pickering, MC Rohrer, B Holers, VM AF Thurman, Joshua M. Kulik, Liudmila Orth, Heather Wong, Maria Renner, Brandon Sargsyan, Siranush A. Mitchell, Lynne M. Hourcade, Dennis E. Hannan, Jonathan P. Kovacs, James M. Coughlin, Beth Woodell, Alex S. Pickering, Matthew C. Rohrer, Baerbel Holers, V. Michael TI Detection of complement activation using monoclonal antibodies against C3d SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SITE-DIRECTED MUTAGENESIS; RECEPTOR-TYPE 2; FACTOR-H; MACULAR DEGENERATION; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; CHOROIDAL NEOVASCULARIZATION; ACQUIRED-IMMUNITY; PROTEIN BETA-1H; MICE DEFICIENT; FLUID-PHASE AB During complement activation the C3 protein is cleaved, and C3 activation fragments are covalently fixed to tissues. Tissue-bound C3 fragments are a durable biomarker of tissue inflammation, and these fragments have been exploited as addressable binding ligands for targeted therapeutics and diagnostic agents. We have generated cross-reactive murine monoclonal antibodies against human and mouse C3d, the final C3 degradation fragment generated during complement activation. We developed 3 monoclonal antibodies (3d8b, 3d9a, and 3d29) that preferentially bind to the iC3b, C3dg, and C3d fragments in solution, but do not bind to intact C3 or C3b. The same 3 clones also bind to tissue-bound C3 activation fragments when injected systemically. Using mouse models of renal and ocular disease, we confirmed that, following systemic injection, the antibodies accumulated at sites of C3 fragment deposition within the glomerulus, the renal tubulointerstitium, and the posterior pole of the eye. To detect antibodies bound within the eye, we used optical imaging and observed accumulation of the antibodies within retinal lesions in a model of choroidal neovascularization (CNV). Our results demonstrate that imaging methods that use these antibodies may provide a sensitive means of detecting and monitoring complement activation-associated tissue inflammation. C1 [Thurman, Joshua M.; Kulik, Liudmila; Orth, Heather; Wong, Maria; Renner, Brandon; Sargsyan, Siranush A.; Hannan, Jonathan P.; Kovacs, James M.; Holers, V. Michael] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Mitchell, Lynne M.; Hourcade, Dennis E.] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA. [Coughlin, Beth; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Woodell, Alex S.; Rohrer, Baerbel] Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC USA. [Pickering, Matthew C.] Univ London Imperial Coll Sci Technol & Med, Ctr Complement & Inflammat Res, London SW7 2AZ, England. [Rohrer, Baerbel] Med Univ S Carolina, Dept Neurosci, Div Res, Charleston, SC 29425 USA. RP Thurman, JM (reprint author), Univ Colorado Denver, Sch Med, Div Nephrol & Hypertens, B-115,POB 6511, Aurora, CO 80045 USA. EM Joshua.Thurman@ucdenver.edu OI Pickering, Matthew/0000-0002-1153-0192; Hannan, Jonathan/0000-0003-3318-2341 FU Alexion Pharmaceuticals, Inc.; Beckman Initiative for Macular Research; KIDNEEDS Foundation; NIH [R01 AR51749, R01 DK076690, R01 AI051436] FX Joshua M. Thurman and V. Michael Holers are paid consultants for Alexion Pharmaceuticals, Inc. A patent application has been filed for the monoclonal antibodies described in this manuscript.; We thank Shaun Bevers at the University of Colorado Biophysics Core for technical assistance. This work was supported in part by the Beckman Initiative for Macular Research (to V.M. Holers), the KIDNEEDS Foundation (to J.M. Thurman), NIH grants R01 AR51749 (to V.M. Holers), R01 DK076690 (to J.M. Thurman), and R01 AI051436 (to D.E. Hourcade), and a sponsored research agreement with Alexion Pharmaceuticals, Inc. NR 48 TC 16 Z9 16 U1 2 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 MAY PY 2013 VL 123 IS 5 BP 2218 EP 2230 DI 10.1172/JCI65861 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 145OA UT WOS:000319025100040 PM 23619360 ER PT J AU Li, N Wu, XF Holzer, RG Lee, JH Todoric, J Park, EJ Ogata, H Gukovskaya, AS Gukovsky, I Pizzo, DP VandenBerg, S Tarin, D Atay, C Arkan, MC Deerinck, TJ Moscat, J Diaz-Meco, M Dawson, D Erkan, M Kleeff, J Karin, M AF Li, Ning Wu, Xuefeng Holzer, Ryan G. Lee, Jun-Hee Todoric, Jelena Park, Eek-Joong Ogata, Hisanobu Gukovskaya, Anna S. Gukovsky, Ilya Pizzo, Donald P. VandenBerg, Scott Tarin, David Atay, Cigdem Arkan, Melek C. Deerinck, Thomas J. Moscat, Jorge Diaz-Meco, Maria Dawson, David Erkan, Mert Kleeff, Joerg Karin, Michael TI Loss of acinar cell IKK alpha triggers spontaneous pancreatitis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; NF-KAPPA-B; UNFOLDED PROTEIN RESPONSE; TRYPSINOGEN ACTIVATION; OXIDATIVE STRESS; AUTOPHAGY; P62; CANCER; INFLAMMATION; MOUSE AB Chronic pancreatitis is an inflammatory disease that causes progressive destruction of pancreatic acinar cells and, ultimately, loss of pancreatic function. We investigated the role of I kappa B kinase alpha (IKK alpha) in pancreatic homeostasis. Pancreas-specific ablation of IKK alpha (Ikk alpha(Delta pan)) caused spontaneous and progressive acinar cell vacuolization and death, interstitial fibrosis, inflammation, and circulatory release of pancreatic enzymes, clinical signs resembling those of human chronic pancreatitis. Loss of pancreatic IKK alpha causes defective autophagic protein degradation, leading to accumulation of p62-mediated protein aggregates and enhanced oxidative and ER stress in acinar cells, but none of these effects is related to NF-kappa B. Pancreas-specific p62 ablation prevented ER and oxidative stresses and attenuated pancreatitis in Ikk alpha(Delta pan) mice, suggesting that cellular stress induced by p62 aggregates promotes development of pancreatitis. Importantly, downregulation of IKK alpha and accumulation of p62 aggregates were also observed in chronic human pancreatitis. Our studies demonstrate that IKK alpha, which may control autophagic protein degradation through its interaction with ATG16L2, plays a critical role in maintaining pancreatic acinar cell homeostasis, whose dysregulation promotes pancreatitis through p62 aggregate accumulation. C1 [Li, Ning; Wu, Xuefeng; Holzer, Ryan G.; Lee, Jun-Hee; Todoric, Jelena; Park, Eek-Joong; Ogata, Hisanobu; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Li, Ning; Wu, Xuefeng; Holzer, Ryan G.; Lee, Jun-Hee; Todoric, Jelena; Park, Eek-Joong; Ogata, Hisanobu; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pathol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA. [Todoric, Jelena] Med Univ Vienna, Dept Lab Med, Vienna, Austria. [Gukovskaya, Anna S.; Gukovsky, Ilya] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gukovskaya, Anna S.; Gukovsky, Ilya] Univ Calif Los Angeles, Los Angeles, CA USA. [Pizzo, Donald P.; VandenBerg, Scott; Tarin, David] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Atay, Cigdem; Arkan, Melek C.] Tech Univ Munich, Klinikum Rechts Isar, Dept Med 2, D-80290 Munich, Germany. [Deerinck, Thomas J.] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA. [Moscat, Jorge; Diaz-Meco, Maria] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Dawson, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Erkan, Mert; Kleeff, Joerg] Tech Univ Munich, Klinikum Rechts Isar, Dept Gen Surg, D-80290 Munich, Germany. RP Karin, M (reprint author), Univ Calif San Diego, 9500 Gilman Dr,Mail Code 0723,Leichtag Bldg,Room, La Jolla, CA 92093 USA. EM karinoffice@ucsd.edu RI Kleeff, Jorg/B-2124-2009; Dawson, David/I-5917-2014 OI Kleeff, Jorg/0000-0003-3432-6669; FU NIH [P50 AA011999, AI043477, CA163798, CA167120]; Pancreatic Cancer Research Lustgarten Foundation grant [RFP-B-007]; Susan G. Komen for the Cure [KG111506]; Austrian Science Fund's Erwin Schroedinger Fellowship [J 3233] FX This work was supported by NIH grants P50 AA011999 (Pilot Project to M. Karin), AI043477 (to M. Karin), CA163798 (to M. Karin), and CA167120 (to N. Li) and by Pancreatic Cancer Research Lustgarten Foundation grant RFP-B-007 (to M. Karin). X. Wu was supported by a postdoctoral fellowship from Susan G. Komen for the Cure (KG111506). J. Todoric was supported by the Austrian Science Fund's Erwin Schroedinger Fellowship (Project# J 3233). We thank S.L. Gonias, D. Brenner, M. Erkan, J. Kleeff, and F.R. Greten for help in procuring human pancreatitis samples and for helpful advice; J. Xiao for technical assistance; and M.G. Farquhar and M. Niwa for helpful discussions regarding lysosomes and ER stress, respectively. We also thank Santa Cruz Biotechnology Inc. and Cell Signaling for antibody samples. NR 62 TC 33 Z9 35 U1 0 U2 6 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 MAY PY 2013 VL 123 IS 5 BP 2231 EP 2243 DI 10.1172/JCI64498 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 145OA UT WOS:000319025100041 PM 23563314 ER PT J AU Schlegel, J Sambade, MJ Sather, S Moschos, SJ Tan, AC Winges, A DeRyckere, D Carson, CC Trenthath, DG Tentler, JJ Eckhardt, SG Kuan, PF Hamilton, RL Duncan, LM Miller, CR Nikolaishvili-Feinberg, N Midkiff, BR Liu, J Zhang, WH Yang, C Wang, XD Frye, SV Earp, HS Shields, JM Graham, DK AF Schlegel, Jennifer Sambade, Maria J. Sather, Susan Moschos, Stergios J. Tan, Aik-Choon Winges, Amanda DeRyckere, Deborah Carson, Craig C. Trenthath, Dimitri G. Tentler, John J. Eckhardt, S. Gail Kuan, Pei-Fen Hamilton, Ronald L. Duncan, Lyn M. Miller, C. Ryan Nikolaishvili-Feinberg, Nana Midkiff, Bentley R. Liu, Jing Zhang, Weihe Yang, Chao Wang, Xiaodong Frye, Stephen V. Earp, H. Shelton Shields, Janie M. Graham, Douglas K. TI MERTK receptor tyrosine kinase is a therapeutic target in melanoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; RAF INHIBITOR RESISTANCE; TUMOR PROGRESSION; APOPTOTIC CELLS; UP-REGULATION; EXPRESSION; CANCER; AXL; CLEARANCE; MUTATIONS AB Metastatic melanoma is one of the most aggressive forms of cutaneous cancers. Although recent therapeutic advances have prolonged patient survival, the prognosis remains dismal. C-MER proto-oncogene tyrosine kinase (MERTK) is a receptor tyrosine kinase with oncogenic properties that is often overexpressed or activated in various malignancies. Using both protein immunohistochemistry and microarray analyses, We demonstrate that MERTK expression correlates with disease progression. MERTK expression was highest in metastatic melanomas, followed by primary melanomas, while the lowest expression was observed in nevi. Additionally, over half of melanoma cell lines overexpressed MERTK compared with normal human melanocytes; however, overexpression did not correlate with mutations in BRAF or RAS. Stimulation of melanoma cells with the MERTK ligand. GAS6 resulted in the activation of several downstream signaling pathways including MAPK/ERK, PI3K/AKT, and JAK/STAT. MERTK inhibition via shRNA reduced MERTK-mediated downstream signaling, reduced colony formation by up to 59%, and diminished tumor volume by 60% in a human melanoma murine xenograft model. Treatment of melanoma cells with UNC1062, a novel MERTK-selective small-molecule tyrosine kinase inhibitor, reduced activation of MERTK-mediated downstream signaling, induced apoptosis in culture, reduced colony formation in soft agar, and inhibited invasion of melanoma cells. This work establishes MERTK as a therapeutic target in melanoma and provides a rationale for the continued development of MERTK-targeted therapies. C1 [Schlegel, Jennifer; Sather, Susan; Winges, Amanda; DeRyckere, Deborah; Graham, Douglas K.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Sambade, Maria J.; Moschos, Stergios J.; Kuan, Pei-Fen; Miller, C. Ryan; Nikolaishvili-Feinberg, Nana; Frye, Stephen V.; Earp, H. Shelton; Shields, Janie M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Moschos, Stergios J.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Tan, Aik-Choon; Tentler, John J.; Eckhardt, S. Gail] Univ Colorado, Sch Med, Div Med Oncol, Aurora, CO USA. [Carson, Craig C.; Shields, Janie M.] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA. [Trenthath, Dimitri G.; Miller, C. Ryan] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Kuan, Pei-Fen] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Hamilton, Ronald L.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Duncan, Lyn M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Miller, C. Ryan; Midkiff, Bentley R.] Univ N Carolina, Translat Pathol Core Lab, Chapel Hill, NC USA. [Liu, Jing; Zhang, Weihe; Wang, Xiaodong; Frye, Stephen V.] Univ N Carolina, Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC USA. [Liu, Jing; Zhang, Weihe; Wang, Xiaodong; Frye, Stephen V.] Univ N Carolina, Sch Med, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC USA. [Yang, Chao] Anichem Inc, North Brunswick, NJ USA. [Shields, Janie M.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. RP Graham, DK (reprint author), Dept Pediat, P18-4401,Mail Stop 8302,12800 East 19th Ave, Aurora, CO 80045 USA. EM doug.graham@ucdenver.edu RI liu, jing/G-3957-2011; Zhang, Weihe/A-3156-2011; Tan, Aik Choon/A-3135-2011; Miller, Ryan/B-9365-2008; OI Zhang, Weihe/0000-0001-5867-6407; Miller, Ryan/0000-0002-0096-8762; Tan, Aik Choon/0000-0003-2955-8369 FU National Cancer Institute [HHSN261200800001E, 3P30CA016086]; American Cancer Society [RGS082910121B]; National Institutes of Health [RO1CA137078, CA115888, ES014635]; American Brain Tumor Basic Research Fellowship; UNC University Cancer Research Fund (UCRF) FX This work was supported in part by grants from the National Cancer Institute (contract no. HHSN261200800001E), American Cancer Society (RGS082910121B, to D.K. Graham), National Institutes of Health (RO1CA137078, to D.K. Graham; CA115888 and ES014635, to J. Shields), and the American Brain Tumor Basic Research Fellowship in honor of Mark Linder (to M.J. Sambade). The UNC Translational Pathology Laboratory is supported in part by grants from the National Cancer Institute (3P30CA016086) and the UNC University Cancer Research Fund (UCRF). The authors wish to thank Randall Wong of the University of Colorado DERC Molecular Biology Core (NTH P30 DK57516) for cell line authentication; Christine Childs of the University of Colorado Cancer Center Flow Cytometry Shared Resource for technical assistance; and Charlene Santos of the UNC-CH LCCC Animal Studies Facility for conducting animal experiments using human melanoma xenografts. NR 39 TC 45 Z9 46 U1 1 U2 20 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 MAY PY 2013 VL 123 IS 5 BP 2257 EP 2267 DI 10.1172/JCI67816 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 145OA UT WOS:000319025100043 PM 23585477 ER PT J AU Ramirez, AS Freres, D Martinez, LS Lewis, N Bourgoin, A Kelly, BJ Lee, CJ Nagler, R Schwartz, JS Hornik, RC AF Ramirez, A. Susana Freres, Derek Martinez, Lourdes S. Lewis, Nehama Bourgoin, Angel Kelly, Bridget J. Lee, Chul-Joo Nagler, Rebekah Schwartz, J. Sanford Hornik, Robert C. TI Information Seeking From Media and Family/Friends Increases the Likelihood of Engaging in Healthy Lifestyle Behaviors SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER NEWS COVERAGE; PLANNED BEHAVIOR; PHYSICAL-ACTIVITY; UNITED-STATES; PREVENTION; INTENTION; SERVICE; RISK; VARIABLES AB The amount of cancer-related information available to the general population continues to grow; yet, its effects are unclear. This study extends previous cross-sectional research establishing that cancer information seeking across a variety of sources is extensive and positively associated with engaging in health-related behaviors. The authors studied how active information seeking about cancer prevention influenced three healthy lifestyle behaviors using a 2-round nationally representative sample of adults ages 4070 years (n=1,795), using propensity scoring to control for potential confounders including baseline behavior. The adjusted odds of dieting at follow-up were 1.51 (95% CI: 1.05, 2.19) times higher for those who reported baseline seeking from media and interpersonal sources relative to nonseekers. Baseline seekers ate 0.59 (95% CI: 0.28, 0.91) more fruits and vegetable servings per day and exercised 0.36 (95% CI: 0.12, 0.60) more days per week at 1-year follow-up compared with nonseekers. The effects of seeking from media and friends/family on eating fruits and vegetables and exercising were independent of seeking from physicians. The authors offer several explanations for why information seeking predicts healthy lifestyle behaviors: information obtained motivates these behaviors; information sought teaches specific techniques; and the act of information seeking may reinforce a psychological commitment to dieting, eating fruits and vegetables, and exercising. C1 [Ramirez, A. Susana] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Freres, Derek; Bourgoin, Angel; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA 19104 USA. [Martinez, Lourdes S.] Michigan State Univ, E Lansing, MI 48824 USA. [Lewis, Nehama] Florida Int Univ, Miami, FL 33199 USA. [Kelly, Bridget J.] RTI Int, Washington, DC USA. [Lee, Chul-Joo] Ohio State Univ, Sch Commun, Columbus, OH 43210 USA. [Nagler, Rebekah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schwartz, J. Sanford] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Schwartz, J. Sanford] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Ramirez, AS (reprint author), NCI, Canc Prevent Fellowship Program, 6130 Execut Blvd,Room 4051A, Bethesda, MD 20892 USA. EM a.susana.ramirez@gmail.com OI Hornik, Robert/0000-0002-2148-8805 FU NCI NIH HHS [P20 CA095856, P50 CA095856, P50-CA095856-05] NR 42 TC 18 Z9 19 U1 3 U2 27 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PD MAY 1 PY 2013 VL 18 IS 5 BP 527 EP 542 DI 10.1080/10810730.2012.743632 PG 16 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 136HO UT WOS:000318353200004 PM 23472825 ER PT J AU Chuang, PY Menon, MC He, JC AF Chuang, Peter Y. Menon, Madhav C. He, John C. TI Molecular targets for treatment of kidney fibrosis SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE Kidney; Fibrosis; HIPK2; Signaling pathways; Treatment ID GROWTH-FACTOR-BETA; NF-KAPPA-B; RENAL INTERSTITIAL FIBROSIS; PROXIMAL TUBULAR CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; SUBTOTALLY NEPHRECTOMIZED RATS; INDUCED COLLAGEN EXPRESSION; GLOMERULAR-FILTRATION-RATE; MATRIX GENE-EXPRESSION; TGF-BETA AB Renal fibrosis is the culmination of processes driven by signaling pathways involving transforming growth factor-beta family of cytokines, connective-tissue growth factor, nuclear factor kappa B, Wnt/beta-catenin, Notch, and other growth factors. Many studies in experimental animal models have directly targeted these pathways and demonstrated efficacy in mitigating renal fibrosis. However, only a small fraction of these approaches have been attempted in human and even fewer have been successfully translated to clinical use for patient with kidney diseases. Drugs with proven efficacy for treatment of kidney diseases and tissue fibrosis exert some of their effects by interfering with components of these pathways. This review considers key molecular mediators of renal fibrosis and their potential as targets for treatment of renal fibrosis. C1 [Chuang, Peter Y.; Menon, Madhav C.; He, John C.] Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. [He, John C.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Chuang, PY (reprint author), Mt Sinai Sch Med, Div Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM peter.chuang@mssm.edu FU NIH [1R01DK078897, 1R01DK088541-01A1, 5K08DK082760]; Veterans Affairs Merit Review Award [1I01BX000345] FX Due to space limitations, the authors could not individually acknowledge work of many investigators in the field of renal fibrosis. We have cited articles that review multiple publications on a topic and we encourage the readers to use them as sources for further study. JCH is supported by NIH 1R01DK078897 and 1R01DK088541-01A1 and a Veterans Affairs Merit Review Award 1I01BX000345; PYC is supported by NIH 5K08DK082760. NR 136 TC 29 Z9 33 U1 4 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 EI 1432-1440 J9 J MOL MED JI J. Mol. Med. PD MAY PY 2013 VL 91 IS 5 BP 549 EP 559 DI 10.1007/s00109-012-0983-z PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 140XT UT WOS:000318690500003 PM 23179685 ER PT J AU Ratti, E Bettica, P Alexander, R Archer, G Carpenter, D Evoniuk, G Gomeni, R Lawson, E Lopez, M Millns, H Rabiner, EA Trist, D Trower, M Zamuner, S Krishnan, R Fava, M AF Ratti, Emiliangelo Bettica, Paolo Alexander, Robert Archer, Graeme Carpenter, David Evoniuk, Gary Gomeni, Roberto Lawson, Erica Lopez, Monica Millns, Helen Rabiner, Eugenii A. Trist, David Trower, Michael Zamuner, Stefano Krishnan, Ranga Fava, Maurizio TI Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE Depression; receptor occupancy; neurokinin; substance P; clinical trials ID SUBSTANCE-P RECEPTORS; DOUBLE-BLIND; FUNCTIONING QUESTIONNAIRE; SEXUAL DYSFUNCTION; MAJOR DEPRESSION; DRUG DEVELOPMENT; RATING-SCALE; MICE LACKING; ANTAGONIST; NK1 AB Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD). Displacement of central [C-11]GR205171 binding indicated that oral orvepitant doses of 30-60 mg/day provided >99% receptor occupancy for >= 24 h. Studies 733 and 833 randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM-D)>= 22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day or placebo (1: 1: 1). Primary outcome measure was change from baseline in 17-item HAM-D total score at Week 6 analyzed using mixed models repeated measures. Study 733 (n=328) demonstrated efficacy on the primary endpoint (estimated drug-placebo differences of 30 mg: -2.41, 95% confidence interval (CI) (-4.50 to -0.31) p=0.0245; 60 mg: -2.86, 95% CI (-4.97 to -0.75) p=0.0082). Study 833 (n=345) did not show significance (estimated drug-placebo differences of 30 mg: -1.67, 95% CI (-3.73 to 0.39) p=0.1122; 60 mg: -0.76, 95% CI (-2.85 to 1.32) p=0.4713). The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD. C1 [Ratti, Emiliangelo; Bettica, Paolo; Alexander, Robert; Trist, David; Trower, Michael; Zamuner, Stefano] GlaxoSmithKline, Neurosci Ctr Excellence Drug Discovery, Verona, Italy. [Archer, Graeme; Millns, Helen] GlaxoSmithKline, Neurosci Discovery Biometr, Harlow, Essex, England. [Carpenter, David; Evoniuk, Gary; Lawson, Erica; Lopez, Monica] GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC 27709 USA. [Gomeni, Roberto] GlaxoSmithKline, Pharmacometr, Upper Merion, PA USA. [Rabiner, Eugenii A.] GlaxoSmithKline, Clin Imaging Ctr, London, England. [Krishnan, Ranga] Duke Natl Univ Singapore, Singapore, Singapore. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Evoniuk, G (reprint author), GlaxoSmithKline, Res & Dev, 17-1229,5 Moore Dr, Res Triangle Pk, NC 27709 USA. EM gee19685@gsk.com RI Rabiner, Eugenii/G-6263-2012 OI Rabiner, Eugenii/0000-0003-3612-6687 FU GlaxoSmithKline; Cenerx; Orexigen; Cypress Bioscience; Sonexa; Atentiv; Alta; Roche; Abbot Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite(R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst FX R Krishnan and M Fava acted as paid consultants to GlaxoSmithKline in the design and conduct of these clinical trials.; R Krishnan has also acted as a paid consultant to, and/or holds stock directly or indirectly in Cenerx, Orexigen, Cypress Bioscience, Sonexa, Atentiv, Alta and Roche.; M Fava has the following lifetime disclosures: Research support: Abbot Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite (R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst. Laboratories: Advisory/Consulting: Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Clinical Trials Solutions, LLC; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuronetics, Inc.; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite (R) LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc. NR 42 TC 18 Z9 18 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD MAY PY 2013 VL 27 IS 5 BP 424 EP 434 DI 10.1177/0269881113480990 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 145IZ UT WOS:000319010100003 PM 23539641 ER PT J AU Ellis, C Grubaugh, AL Egede, LE AF Ellis, Charles Grubaugh, Anouk L. Egede, Leonard E. TI Factors Associated with SF-12 Physical and Mental Health Quality of Life Scores in Adults with Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Disability; stroke; quality of life ID EAST MELBOURNE STROKE; SURVIVORS; DETERMINANTS; DEPRESSION; RECOVERY; VALIDITY; IMPACT; RELIABILITY; POSTSTROKE AB Background: Studies of poststroke quality of life (QOL) have not consistently identified which factors are most likely to independently influence the physical and mental aspects of QOL. In this study, we sought to identify which sociodemographic, comorbid disease conditions, and disability factors independently influenced the physical and mental aspects of poststroke QOL. Methods: We completed a cross-sectional study of 666 US adults with a history of stroke from the 2007 Medical Expenditure Panel Survey (MEPS). We used sequentially built multiple linear regression models to identify sociodemographic, comorbidity, and stroke-related disability factors that independently affected short form-12 (SF-12) physical component summary (PCS) and mental component summary (MCS) scores. STATA software (version 10; StataCorp LP, College Station, TX) was used to perform the analysis to account for the complex survey design of the MEPS. Results: In fully adjusted models using a nationally representative sample of US adults, being non-Hispanic black (beta = 3.58), 45 to 64 years of age (beta = -3.48), 65 years of age or older (beta = -2.90), married (beta = -3.50), middle (beta = 2.78) and high income (beta = 3.73), or having hypertension (beta = -2.25), cardiovascular disease (beta = -2.05), arthritis (beta = -4.49), depression (beta = -2.98), physical limitations (beta = -7.60), social limitations (beta = -4.12), and a need for assistance with instrumental activities of daily living (beta = -4.49) were independently correlated with PCS scores. Being 45 to 64 years of age (beta = 3.96), depressed (beta = -15.92), or having social limitations (beta = -3.62) were independently correlated with MCS scores. Conclusions: Sociodemographic, comorbidity, and stroke-related disability factors have differential effect on physical and mental aspects of QOL in poststroke patients. C1 [Ellis, Charles; Grubaugh, Anouk L.; Egede, Leonard E.] Med Univ S Carolina, Vet Affairs Ctr Dis Prevent & Hlth Intervent Dive, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Ellis, Charles] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. RP Ellis, C (reprint author), Med Univ S Carolina, Coll Hlth Profess, 77 President St,MSC 700, Charleston, SC 29425 USA. EM ellisc@musc.edu FU South Carolina HSRD [REA 08-261]; Veterans Health Administration Health Services Research and Development program [07-012-3, 07-015-2] FX Supported by the use of facilities at the Charleston, South Carolina HSR&D-funded Center for Disease Prevention and Health Interventions for Diverse Populations (REA 08-261). Dr Ellis is supported by a career development award (CDA # 07-012-3) from the Veterans Health Administration Health Services Research and Development program. Dr Grubaugh is supported by a career development award (CDA2 # 07-015-2) from the Veterans Health Administration Health Services Research and Development program. NR 36 TC 11 Z9 13 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAY PY 2013 VL 22 IS 4 BP 309 EP 317 DI 10.1016/j.jstrokecerebrovasdis.2011.09.007 PG 9 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 144BX UT WOS:000318915500005 PM 22005038 ER PT J AU Willey, JZ Khatri, P Khoury, JC Merino, JG Ford, AL Rost, NS Gonzales, NR Ali, LK Meyer, BC Broderick, JP AF Willey, Joshua Z. Khatri, Pooja Khoury, Jane C. Merino, Jose G. Ford, Andria L. Rost, Natalia S. Gonzales, Nicole R. Ali, Latisha K. Meyer, Brett C. Broderick, Joseph P. TI Variability in the Use of Intravenous Thrombolysis for Mild Stroke: Experience Across the SPOTRIAS Network SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Mild stroke; stenosis ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE; NEUROLOGICAL-DISORDERS; SCIENTIFIC STATEMENT; NATIONAL-INSTITUTE; EARLY MANAGEMENT; ASSOCIATION; ELIGIBILITY; GUIDELINES; SYMPTOMS AB Background: Current guidelines do not define the lower severity threshold for thrombolysis. In this study, we describe the variability of treatment of mild stroke patients across a network of academic stroke centers. Methods: Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collect data on patients treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), including demographics, pretreatment National Institutes of Health Stroke Scale (NIHSS) scores, and in-hospital mortality. We examined the variability in proportion of total tissue plasminogen activator-treated patients in the NIHSS categories (0-3, 4-5, or >= 6) and associated outcomes. Results: A total of 2514 patients with reported NIHSS scores were treated with IV rt-PA between January 1, 2005 and December 31, 2009. The proportion of patients with mild stroke (NIHSS scores of 0-3) who were treated with IV rt-PA varied substantially across the centers (2.7-18.0%; P < .001). There were 5 deaths in the 256 treated with an NIHSS score of 0-3 (2.0%). The proportion of treated patients across the network with an NIHSS score of 0 to 3 increased from 4.8% in 2005 to 10.7% in 2009 (P = .001). Conclusions: There is substantial variability in the proportion of treated patients who have mild stroke across the SPOTRIAS centers, reflecting a paucity of data on how to best treat patients with mild stroke. Randomized trial data for this group of patients are needed to clarify the use of rt-PA in patients with the mildest strokes. C1 [Willey, Joshua Z.] Columbia Univ, Dept Neurol, New York, NY USA. [Khatri, Pooja; Broderick, Joseph P.] Univ Cincinnati, Cincinnati, OH 45221 USA. [Ford, Andria L.] Washington Univ, St Louis, MO USA. [Gonzales, Nicole R.] Univ Texas Houston, Houston, TX USA. [Ali, Latisha K.] Univ Calif Los Angeles, Los Angeles, CA USA. [Meyer, Brett C.] Univ Calif San Diego, San Diego, CA 92103 USA. [Khoury, Jane C.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH USA. [Merino, Jose G.] NINDS, Sect Stroke Diagnost & Therapeut, Div Intramural Res, Bethesda, MD 20892 USA. [Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Stroke Div, Boston, MA 02114 USA. RP Willey, JZ (reprint author), Dept Neurol, 710 West 168th St,Box 30, New York, NY 10032 USA. EM jzw2@columbia.edu RI Khoury, Jane/O-2068-2015; OI Merino, Jose/0000-0002-6676-0008 FU Intramural Division of the National Institute of Neurological Disorders and Stroke/National Institutes of Health; National Institutes of Neurological Diseases and Stroke [NINDS P50 NS049060]; NINDS [1K23NS073104-01A1] FX Supported in part by the Intramural Division of the National Institute of Neurological Disorders and Stroke/National Institutes of Health. SPOTRIAS is funded by the National Institutes of Neurological Diseases and Stroke (NINDS P50 NS049060). JZW was funded by NINDS 1K23NS073104-01A1. NR 19 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAY PY 2013 VL 22 IS 4 BP 318 EP 322 DI 10.1016/j.jstrokecerebrovasdis.2011.09.005 PG 5 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 144BX UT WOS:000318915500006 PM 22177935 ER PT J AU Nadkarni, NK Studenski, SA Perera, S Rosano, C Aizenstein, HJ Brach, JS Van Swearingen, JM AF Nadkarni, Neelesh K. Studenski, Stephanie A. Perera, Subashan Rosano, Caterina Aizenstein, Howard J. Brach, Jennifer S. Van Swearingen, Jessie M. TI White Matter Hyperintensities, Exercise, and Improvement in Gait Speed: Does Type of Gait Rehabilitation Matter? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE gait; rehabilitation; white matter hyperintensities; subcortical vascular disease; tracts ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; CARDIOVASCULAR HEALTH; COGNITIVE FUNCTION; ELDERLY-PEOPLE; BRAIN; ABNORMALITIES; LESIONS; MRI; DEMENTIA AB Objectives To examine whether white matter hyperintensities (WMHs) on brain magnetic resonance imaging (MRI) in tracts in older adults with mobility impairment are linked to outcomes of gait rehabilitation interventions. Design Twelve-week randomized controlled single-blind trial. Setting University-based mobility research laboratory. Participants Ambulatory adults aged 65 and older with mobility impairment. Intervention A conventional gait intervention focusing on walking, endurance, balance, and strength (WEBS, n=21) and a task-oriented intervention focused on timing and coordination of gait (TC, n=23). Measurements Self-paced gait speed was measured over an instrumented walkway before and after the intervention, and WMH and brain volumes were quantified on preintervention brain MRI using an automated segmentation process. A white matter tract atlas was overlaid on the segmented images to measure tract WMH volumes, and WMH volumes were normalized to total brain volume. Aggregate WMH volumes in all white matter tracts and individual WMH volumes in specific longitudinal tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus, and fronto-occipital fasciculus) and the cingulum were measured. Results Gait speed gains in the TC group were of the same magnitude, independent of WMH volume measures in all except the cingulum, but in the WEBS group, gain in gait speed was smaller with greater overall tract WMH volumes (P<.001) and with greater WMH volume in the three longitudinal tracts (P<.001 to .02). Conclusion Gains in gait speed with two types of gait rehabilitation are associated with individual differences in WMHs. Task-oriented therapy that targets timing and coordination of gait may particularly benefit older adults with WMHs in brain tracts that influence gait and cognition. C1 [Nadkarni, Neelesh K.; Studenski, Stephanie A.; Perera, Subashan] Univ Pittsburgh, Dept Med, Div Geriatr Med & Gerontol, Pittsburgh, PA 15213 USA. [Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Aizenstein, Howard J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Brach, Jennifer S.; Van Swearingen, Jessie M.] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15213 USA. RP Nadkarni, NK (reprint author), Univ Pittsburgh, Dept Med, Div Geriatr Med & Gerontol, Suite 500,3471 5th Ave,Kaufman Med Bldg, Pittsburgh, PA 15213 USA. EM nkn3@pitt.edu RI Perera, Subashan/D-7603-2014; OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Pittsburgh Claude D. Pepper Older American's Independence Center [P30 AG024827]; Ortho Biotech; Lilly; Merck FX This study was supported by Pittsburgh Claude D. Pepper Older American's Independence Center Grant P30 AG024827. We appreciate the assistance of Rebecca L. MacCloud for providing the figure inserts for the brain tracts.; None of the authors have any financial, personal, or potential conflict of interest with the material presented in this article. Subhashan Perera and Stephanie A. Studenski have received past research grants and funding from Ortho Biotech, Lilly, and Merck. NR 58 TC 11 Z9 11 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2013 VL 61 IS 5 BP 686 EP 693 DI 10.1111/jgs.12211 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 145GB UT WOS:000319002100002 PM 23590257 ER PT J AU Reeves, ST Finley, AC Skubas, NJ Swaminathan, M Whitley, WS Glas, KE Hahn, RT Shanewise, JS Adams, MS Shernan, SK AF Reeves, Scott T. Finley, Alan C. Skubas, Nikolaos J. Swaminathan, Madhav Whitley, William S. Glas, Kathryn E. Hahn, Rebecca T. Shanewise, Jack S. Adams, Mark S. Shernan, Stanton K. CA Amer Soc Echocardiography Amer Soc Echocardiography Soc Cardiovasc Anesthesiologists TI Basic Perioperative Transesophageal Echocardiography Examination: A Consensus Statement of 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; Basic certification ID BLUNT CHEST TRAUMA; TRANS-ESOPHAGEAL ECHOCARDIOGRAPHY; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; CARDIAC SURGICAL-PATIENTS; CAPILLARY WEDGE PRESSURE; PARADOXICAL AIR-EMBOLISM; ACUTE PULMONARY-EMBOLISM; CRITICALLY ILL PATIENTS; INTENSIVE-CARE-UNIT; TASK-FORCE C1 [Reeves, Scott T.; Finley, Alan C.] Med Univ S Carolina, Charleston, SC USA. [Skubas, Nikolaos J.] Weill Cornell Med Coll, New York, NY USA. [Swaminathan, Madhav] Duke Univ, Durham, NC USA. [Shernan, Stanton K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Whitley, William S.; Glas, Kathryn E.] Emory Univ, Atlanta, GA 30322 USA. [Hahn, Rebecca T.; Shanewise, Jack S.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Adams, Mark S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reeves, ST (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. NR 80 TC 32 Z9 33 U1 1 U2 75 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 MAY PY 2013 VL 26 IS 5 BP 443 EP 456 DI 10.1016/j.echo.2013.02.015 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 143YV UT WOS:000318906400001 PM 23622926 ER PT J AU Psaila, B Bussel, JB Frelinger, AL Michelson, AD AF Psaila, B. Bussel, J. B. Frelinger, A. L. Michelson, A. D. TI Differences in platelet function in patients with acute myeloid leukemia and myelodysplasia compared to equally thrombocytopenic patients with immune thrombocytopenia: a reply to a rebuttal SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Letter C1 [Psaila, B.] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London, England. [Bussel, J. B.] Weill Cornell Med Coll, Div Pediat Hematol Oncol, Platelet Disorders Ctr, New York, NY 10065 USA. [Frelinger, A. L.; Michelson, A. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Boston Childrens Hosp, Div Hematol Oncol,Ctr Platelet Res Studies, Boston, MA 02115 USA. RP Bussel, JB (reprint author), Weill Cornell Med Coll, Div Pediat Hematol Oncol, Platelet Disorders Ctr, 525 East 68th St,Payson Pavil 695, New York, NY 10065 USA. EM jbussel@cornell.med.edu OI Psaila, Beth/0000-0001-8198-9663 NR 3 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD MAY PY 2013 VL 11 IS 5 BP 1002 EP 1003 DI 10.1111/jth.12191 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 145JQ UT WOS:000319011900026 PM 23496753 ER PT J AU Percac-Lima, S Benner, CS Lui, R Aldrich, LS Oo, SA Regan, N Chabner, BA AF Percac-Lima, Sanja Benner, Carly S. Lui, Raymond Aldrich, Leslie S. Oo, Sarah A. Regan, Nessa Chabner, Bruce A. TI The Impact of a Culturally Tailored Patient Navigator Program on Cervical Cancer Prevention in Latina Women SO JOURNAL OF WOMENS HEALTH LA English DT Article ID INCOME MINORITY WOMEN; ABNORMAL PAP-SMEARS; IMPROVING FOLLOW-UP; URBAN-POPULATION; INTERVENTION; ADHERENCE; COLPOSCOPY; BARRIERS; RISK; SCIENCE AB Background: Cervical cancer disproportionately affects Latina women in the United States. This study evaluated the impact of patient navigation on cervical cancer prevention in Latinas. Methods: Between January 2004 and April 2011, 533 Latina women with an abnormal Pap smear requiring colposcopy received patient navigation from their healthcare center in Chelsea, Massachusetts, to the Massachusetts General Hospital (MGH). The comparison group comprised 253 non-navigated Latinas from other primary care practices at MGH referred to the same MGH colposcopy clinic. Primary outcomes were the percentage of missed colposcopy appointments, time to colposcopy, and changes in the severity of cervical pathology at colposcopy over two time periods, 2004-2007 and 2008-2011. Results: The mean age in both groups was 35 years (range 22-86). Navigated women had fewer missed colposcopy appointments over time, with the average falling from 19.8% to 15.7% (p = 0.024), compared with an insignificant increase in the no-show rates from 18.6% to 20.6% (p = 0.454) in the comparison group. The difference in the no-show rate trend over time between the groups was significant (p < 0.001). The time to colposcopy did not change in either group, though trends over time demonstrated a shorter follow-up for navigated women (p = 0.010). The grade of cervical abnormality among navigated women decreased from a numerical score of 2.03 to 1.83 (p = 0.035) over the two time intervals, while the severity of pathological score in the non-navigated group did not change significantly from 1.83 to 1.92 (p = 0.573) in the same interval. Comparison of trends in pathological score over time showed a decrease in the severity of cervical abnormality for navigated participants compared to the non-navigated group (p < 0.001). Conclusion: Patient navigation can prevent cervical cancer in Latina women by increasing colposcopy clinic attendance, shortening time to colposcopy, and decreasing severity of cervical abnormalities over time. C1 [Percac-Lima, Sanja; Oo, Sarah A.] MGH Chelsea HealthCare Ctr, Chelsea, MA 02150 USA. [Percac-Lima, Sanja; Benner, Carly S.; Lui, Raymond; Chabner, Bruce A.] Harvard Univ, Sch Med, Boston, MA USA. [Lui, Raymond] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Percac-Lima, Sanja; Aldrich, Leslie S.; Oo, Sarah A.; Regan, Nessa] Massachusetts Gen Hosp, Ctr Community Hlth Improvement, Boston, MA 02114 USA. [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Percac-Lima, S (reprint author), MGH Chelsea HealthCare Ctr, 151 Everett Ave, Chelsea, MA 02150 USA. EM spercaclima@partners.org FU Proctor and Gamble; Agency for Healthcare Research and Quality [1R18 HS019161-01] FX The authors would like to thank Diana Maldonado the cervical patient navigator and her supervisor Denise Sidorowicz, NP, for their work on the program. The authors are grateful to Steven Atlas, MD, MPH, for support and review of the manuscript. The study was funded by a grant from Proctor and Gamble to the MGH Chelsea Cervical Outreach Program. Dr. Percac-Lima was supported in part by a grant from the Agency for Healthcare Research and Quality (1R18 HS019161-01). It was presented at the New England Meeting of the Society of General Medicine in Portland, Maine on March 23, 2012 and at the Annual Meeting of the Society of General Medicine in Orlando, Florida on May 9, 2012. NR 38 TC 13 Z9 13 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2013 VL 22 IS 5 BP 426 EP 431 DI 10.1089/jwh.2012.3900 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 142FC UT WOS:000318781000007 PM 23621746 ER PT J AU Miller, TM Pestronk, A David, W Rothstein, J Simpson, E Appel, SH Andres, PL Mahoney, K Allred, P Alexander, K Ostrow, LW Schoenfeld, D Macklin, EA Norris, DA Manousakis, G Crisp, M Smith, R Bennett, CF Bishop, KM Cudkowicz, ME AF Miller, Timothy M. Pestronk, Alan David, William Rothstein, Jeffrey Simpson, Ericka Appel, Stanley H. Andres, Patricia L. Mahoney, Katy Allred, Peggy Alexander, Katie Ostrow, Lyle W. Schoenfeld, David Macklin, Eric A. Norris, Daniel A. Manousakis, Georgios Crisp, Matthew Smith, Richard Bennett, C. Frank Bishop, Kathie M. Cudkowicz, Merit E. TI An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study SO LANCET NEUROLOGY LA English DT Article ID SUPEROXIDE-DISMUTASE; WILD-TYPE; DISEASE; THERAPY; ALS AB Background Mutations in SOD1 cause 13% of familial amyotrophic lateral sclerosis. In the SOD1 Gly93Ala rat model of amyotrophic lateral sclerosis, the antisense oligonucleotide ISIS 333611 delivered to CSF decreased SOD1 mRNA and protein concentrations in spinal cord tissue and prolonged survival. We aimed to assess the safety, tolerability, and pharmacokinetics of ISIS 333611 after intrathecal administration in patients with SOD1-related familial amyotrophic lateral sclerosis. Methods In this randomised, placebo-controlled, phase 1 trial, we delivered ISIS 333611 by intrathecal infusion using an external pump over 11.5 h at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, 3.00 mg) to four cohorts of eight patients with SOD1-positive amyotrophic lateral sclerosis (six patients assigned to ISIS 333611, two to placebo in each cohort). We did the randomisation with a web-based system, assigning patients in blocks of four. Patients and investigators were masked to treatment assignment. Participants were allowed to re-enrol in subsequent cohorts. Our primary objective was to assess the safety and tolerability of ISIS 333611. Assessments were done during infusion and over 28 days after infusion. This study was registered with Clinicaltrials.gov, number NCT01041222. Findings Seven of eight (88%) patients in the placebo group versus 20 of 24 (83%) in the ISIS 333611 group had adverse events. The most common events were post-lumbar puncture syndrome (3/8 [38%] vs 8/24 [33%]), back pain (4/8 [50%] vs 4/24 [17%]), and nausea (0/8 [0%] vs 3/24 [13%]). We recorded no dose-limiting toxic effects or any safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611. Re-enrolment and re-treatment were also well tolerated. Interpretation This trial is the first clinical study of intrathecal delivery of an antisense oligonucleotide. ISIS 333611 was well tolerated when administered as an intrathecal infusion. Antisense oligonucleotides delivered to the CNS might be a feasible treatment for neurological disorders. C1 [Miller, Timothy M.; Pestronk, Alan; Manousakis, Georgios; Crisp, Matthew] Washington Univ, Sch Med, St Louis, MO 63110 USA. [David, William; Andres, Patricia L.; Mahoney, Katy; Allred, Peggy; Schoenfeld, David; Macklin, Eric A.; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Rothstein, Jeffrey; Ostrow, Lyle W.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Simpson, Ericka; Appel, Stanley H.] Methodist Neurol Inst, Houston, TX USA. [Smith, Richard] Ctr Neurol Study, La Jolla, CA USA. [Alexander, Katie; Norris, Daniel A.; Bennett, C. Frank; Bishop, Kathie M.] ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Miller, TM (reprint author), Washington Univ, 115 Biotech Bldg,Box 8111,660 S Euclid, St Louis, MO 63110 USA. EM millert@neuro.wustl.edu OI Macklin, Eric/0000-0003-1618-3502 FU NIH; Muscular Dystrophy Association; Neuromuscular Research Fund; Insmed; Knopp; Cytokinetics; Biogen Idec; ISIS; Genzyme; GlaxoSmithKline; Ultragenyx; Sanofi; ALSA; MDA; Biogen; Psyadon Pharmaceuticals; Isis Pharmaceuticals; Tau consortium; Mallinckrodt Foundation; Cure PSP; Washington University Hope Center; ALS; Johns Hopkins Packard Center; Washington University ICTS; The ALS Association; National Institute of Neurological Disorders and Stroke (NIH) [K08NS074194, R01NS078398]; Washington University Institute of Clinical and Translational Sciences [UL1 TR000448]; National Center for Advancing Translational Sciences (NIH); Grifols; Gamunex FX Funding The ALS Association, Muscular Dystrophy Association, Isis Pharmaceuticals.; KA, DN, KMB, and CFB are employees of Isis Pharmaceuticals. Isis Pharmaceuticals provided support for this trial and provides antisense oligonucleotides to TMM for animal studies. RS, CFB, the Center for Neurologic Study, and Isis Pharmaceuticals have filed a patent for use of the ISIS 333611. ES is a paid speaker for Grifols for Gamunex and served on an advisory board for CSL Behring. AP receives revenue related to antibody patent licenses and speaker honoraria from Athena; owns stock in Johnson & Johnson; directs the Washington University Neuromuscular Clinical Laboratory, which does antibody testing; and receives research support from the NIH, Muscular Dystrophy Association, Neuromuscular Research Fund, Insmed, Knopp, Cytokinetics, Biogen Idec, ISIS, Genzyme, GlaxoSmithKline, Ultragenyx, and Sanofi. RS is a consultant for Isis Pharmaceuticals. JR receives grant support from NIH, ALSA, MDA, Cytokinetics, Biogen, and Psyadon Pharmaceuticals. EAM serves on the data and safety monitoring boards for Lantheus Medical Imaging and Shire Human Genetic Therapies. PLA is named as an inventor for patent 7493 812. MEC receives grant support from Isis Pharmaceuticals, Biogen, and Knopp and is a consultant for Teva, Cytokinetics, and Biogen. TMM has received grant support from Isis Pharmaceuticals, NIH, ALSA, MDA, Tau consortium, Mallinckrodt Foundation, Cure PSP, Washington University Hope Center, Project 5 for ALS, Johns Hopkins Packard Center, and Washington University ICTS. DS does extensive consulting for pharmaceutical companies including Aptly Solutions, Agenix, Asubio Pharmaceuticals, Alexion Pharmaceuticals, Cytokinetics, Edison Pharmaceuticals, GlaxoSmith Kline, Merck, NeuroNova, and Pfizer. The other authors declare that they have no conflicts of interest. We thank the patients who participated in this study, and their families and carergivers. This trial was funded by the Muscular Dystrophy Association, The ALS Association, and Isis Pharmaceuticals. TMM was supported by National Institute of Neurological Disorders and Stroke (NIH) grants K08NS074194 and R01NS078398. Clinical studies at Washington University were supported by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448, National Center for Advancing Translational Sciences (NIH). We appreciate the hard work and dedication of many people who contributed to this study: Massachusetts General Hospital Coordinating Center (Kate Jackson, Alex Sherman, Marianne Kearney, Hong Yu, Lauren Schnupp, Bryan Sweet, Jason Walker, Igor Katsovskiy, Ervin Sinani), Massachusetts General Hospital clinical site (Swati Aggarwal, Melanie Majkut, Jennifer Berndt, Darlene Sawicki), Johns Hopkins University School of Medicine (Richard Kimball, Lora Clawson, Kristen Riley), Methodist Neurological Institute (Sharon Halton, Luis Lay), Washington University in St Louis (Julaine Florence, Catherine Siener, Brian Sommerville, Robert Swarm, Leo Wang, Charlie Wulf), Isis Pharmaceuticals (Viola Kam, Jesse Kwoh, Katherine Kwoh, John Madson, Gina McMullin, Dan Schultz). We also thank Robert Brown, Benjamin Brooks, and Don Cleveland for input about clinical study design, the data safety and monitoring board (Walter Bradley, Karl Kieburtz, Carl Leventhal, Michael McDermott, Stephen Reingold), and the many investigators of the Northeast ALS Trials Consortium who referred patients to the study and for Patients Like Me for referrals to Johns Hopkins University. NR 22 TC 144 Z9 145 U1 8 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2013 VL 12 IS 5 BP 435 EP 442 DI 10.1016/S1474-4422(13)70061-9 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 142ZS UT WOS:000318836700014 PM 23541756 ER PT J AU Tala, I Chen, R Hu, T Fitzpatrick, ER Williams, DA Whitehead, IP AF Tala, I. Chen, R. Hu, T. Fitzpatrick, E. R. Williams, D. A. Whitehead, I. P. TI Contributions of the RhoGEF activity of p210 BCR/ABL to disease progression SO LEUKEMIA LA English DT Article DE chronic myelogenous leukemia; p210 BCR/ABL; RhoGEF domain; Rho GTPase ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; MYELOPROLIFERATIVE DISEASE; KINASE-ACTIVITY; TRANSFORMATION; ONCOGENE; DOMAIN; ACTIVATION; CELLS AB We have previously identified a tyrosine kinase-independent, guanine nucleotide exchange factor (GEF) activity, which is contained within the region of p210 no expansion BCR/ABL that distinguishes it from p190 BCR/ABL. In the current study, we have compared the transforming activity of p190 BCR/ABL, p210 BCR/ABL and a mutant that lacks GEF activity (p210 BCR/ABL(S509A)). In cell-based, ex vivo, and murine bone marrow transplantation (BMT) assays the transforming activity of p210 BCR/ABL(S509A) mimics p190 BCR/ABL, and is distinct from p210 BCR/ABL. Thus, in the BMT assay, the p190 BCR/ABL- and p210 BCR/ABL(S509A)-transplanted mice exhibit a more rapid onset of disease than mice transplanted with p210 BCR/ABL. The reduced disease latency is associated with erythroid hyperplasia in the absence of anemia, and expansion of the megakaryocyte-erythrocyte progenitor (MEP), common myeloid progenitor (CMP) and granulocyte-macrophage progenitor (GMP) populations, producing a phenotype that is similar to acute myeloid leukemia (AML-M6). The disease phenotype is readily transplantable into secondary recipients. This is consistent with ex vivo clonogenicity assays, where p210 BCR/ABL preferentially supports the growth of colony forming unit (CFU)-granulocyte-macrophage (GM), whereas p190 BCR/ABL and the mutant preferentially support the growth of burst forming unit-erythroid (BFU-E). These results suggest that the GEF activity that distinguishes p210 BCR/ABL from p190 BCR/ABL actively regulates disease progression. C1 [Tala, I.; Chen, R.; Hu, T.; Fitzpatrick, E. R.; Whitehead, I. P.] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp Canc Ctr, Newark, NJ 07103 USA. [Williams, D. A.] Childrens Hosp Boston, Hematol Oncol Div, Boston, MA USA. [Williams, D. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Whitehead, IP (reprint author), Univ Med & Dent New Jersey, Canc Ctr H Level, 205 South Orange Ave, Newark, NJ 07101 USA. EM whiteip@umdnj.edu RI Hu, Tinghui/F-3213-2015 FU Public Health Service [CA097066, DK62757]; NIH [CA097066, DK62757] FX This work was supported by Public Health Service grants CA097066 (IPW) and DK62757 (DAW). NIH grants CA097066 (IPW) and DK62757 (DAW). NR 38 TC 3 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2013 VL 27 IS 5 BP 1080 EP 1089 DI 10.1038/leu.2012.351 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 141AS UT WOS:000318698300011 PM 23207522 ER PT J AU Goldman, S Smith, L Anderson, JR Perkins, S Harrison, L Geyer, MB Gross, TG Weinstein, H Bergeron, S Shiramizu, B Sanger, W Barth, M Zhi, J Cairo, MS AF Goldman, S. Smith, L. Anderson, J. R. Perkins, S. Harrison, L. Geyer, M. B. Gross, T. G. Weinstein, H. Bergeron, S. Shiramizu, B. Sanger, W. Barth, M. Zhi, J. Cairo, M. S. TI Rituximab and FAB/LMB 96 chemotherapy in children with Stage III/IV B-cell non-Hodgkin lymphoma: a Children's Oncology Group report SO LEUKEMIA LA English DT Letter ID ACUTE-LYMPHOBLASTIC-LEUKEMIA; CHOP CHEMOTHERAPY; ADOLESCENTS; RISK; TRIAL C1 [Goldman, S.] Med City Childrens Hosp, Dept Pediat Hematol Oncol, Dallas, TX USA. [Smith, L.; Anderson, J. R.] Univ Nebraska, Coll Publ Hlth, Dept Biostat, Omaha, NE 68182 USA. [Perkins, S.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Harrison, L.; Cairo, M. S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Geyer, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Gross, T. G.] Ohio State Univ, Dept Pediat Hematol Oncol Blood & Marrow Transpla, Columbus, OH 43210 USA. [Weinstein, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Hematol Oncol, Boston, MA USA. [Bergeron, S.] CHOC Childrens Hosp, Dept Pediat Hematol Oncol, Orange, CA USA. [Shiramizu, B.] Univ Hawaii, Dept Pediat Hematol Oncol, Honolulu, HI 96822 USA. [Sanger, W.] Univ Nebraska, Med Ctr, Dept Cytogenet, Omaha, NE USA. [Barth, M.] Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY 14263 USA. [Zhi, J.] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Cairo, M. S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Cairo, M. S.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Cairo, M. S.] Dept Microbiol, Valhalla, NY USA. [Cairo, M. S.] New York Med Coll, Valhalla, NY 10595 USA. [Cairo, M. S.] New York Med Coll, Dept Cell Biol & Anat, Valhalla, NY 10595 USA. RP Goldman, S (reprint author), Med City Childrens Hosp, Dept Pediat Hematol Oncol, Dallas, TX USA. EM Mitchell_cairo@nymc.edu OI Geyer, Mark/0000-0001-5248-9117 FU NCI NIH HHS [CA98413-09, CA98543-09, U10 CA098413, U10 CA098543]; NIMHD NIH HHS [U54 MD007584] NR 13 TC 32 Z9 35 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2013 VL 27 IS 5 BP 1174 EP 1177 DI 10.1038/leu.2012.255 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 141AS UT WOS:000318698300022 PM 22940833 ER PT J AU Arora, M Pidala, J Cutler, CS Chai, X Kurland, B Jacobsohn, DA Pavletic, SZ Palmer, J Vogelsang, G Jagasia, M Schultz, K Lee, SJ AF Arora, M. Pidala, J. Cutler, C. S. Chai, X. Kurland, B. Jacobsohn, D. A. Pavletic, S. Z. Palmer, J. Vogelsang, G. Jagasia, M. Schultz, K. Lee, S. J. TI Impact of prior acute GVHD on chronic GVHD outcomes: a chronic graft versus host disease consortium study SO LEUKEMIA LA English DT Letter ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; MARROW-TRANSPLANTATION; CLINICAL-TRIALS; CRITERIA; SEVERITY; COHORT C1 [Arora, M.] Univ Minnesota, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA. [Pidala, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Cutler, C. S.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Chai, X.; Kurland, B.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Chai, X.; Kurland, B.; Lee, S. J.] Univ Washington, Seattle, WA 98195 USA. [Jacobsohn, D. A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Palmer, J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Vogelsang, G.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Jagasia, M.] Vanderbilt Univ, Nashville, TN USA. [Schultz, K.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Arora, M (reprint author), Univ Minnesota, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA. EM arora005@umn.edu OI Kurland, Brenda/0000-0002-5669-0595 FU NCI NIH HHS [R01 CA118953, CA 118953, U54 CA163438] NR 15 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2013 VL 27 IS 5 BP 1196 EP 1201 DI 10.1038/leu.2012.292 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 141AS UT WOS:000318698300030 PM 23047477 ER PT J AU Auma, MA Siedner, MJ Nyehangane, D Nalusaji, A Nakaye, M Mwanga-Amumpaire, J Muhindo, R Wilson, LA Il, YB Moore, CC AF Auma, Mary A. Siedner, Mark J. Nyehangane, Dan Nalusaji, Aisha Nakaye, Martha Mwanga-Amumpaire, Juliet Muhindo, Rose Wilson, L. Anthony Il, Yap Boum Moore, Christopher C. TI Malaria is an uncommon cause of adult sepsis in south-western Uganda SO MALARIA JOURNAL LA English DT Article DE Sepsis; Uganda; Africa; Malaria; Adult ID HOSPITALIZED FEBRILE PATIENTS; NORTHERN TANZANIA; MORTALITY; TUBERCULOSIS; POPULATION; ADMISSIONS; MANAGEMENT; DIAGNOSIS; PARASITES; CHILDREN AB Background: Malaria is often considered a cause of adult sepsis in malaria endemic areas. However, diagnostic limitations can make distinction between malaria and other infections challenging. Therefore, the objective of this study was to determine the relative contribution of malaria to adult sepsis in south-western Uganda. Methods: Adult patients with sepsis were enrolled at the Mbarara Regional Referral Hospital between February and May 2012. Sepsis was defined as infection plus >= 2 of the following: axillary temperature >37.5 degrees C or <35.5 degrees C, heart rate >90 or respiratory rate >20. Severe sepsis was defined as sepsis plus organ dysfunction (blood lactate >4 mmol/L, confusion, or a systolic blood pressure <90 mmHg). Sociodemographic, clinical and laboratory data, including malaria PCR and rapid diagnostic tests, as well as acid fast bacteria sputum smears and blood cultures were collected. Patients were followed until in-patient death or discharge. The primary outcome of interest was the cause of sepsis. Multivariable logistic regression was performed to assess predictors of mortality. Results: Enrollment included 216 participants who were 51% female with a median age of 32 years (IQR 27-43 years). Of these, 122 (56%) subjects were HIV-seropositive of whom 75 (66%) had a CD4+ T cell count <100 cells/mu L. The prevalence of malaria was 4% (six with Plasmodium falciparum, two with Plasmodium vivax). Bacteraemia was identified in 41 (19%) patients. In-hospital mortality was 19% (n = 42). In multivariable regression analysis, Glasgow Coma Score <9 (IRR 4.81, 95% CI 1.80-12.8) and severe sepsis (IRR, 2.07, 95% CI 1.03-4.14), but no specific diagnoses were statistically associated with in-hospital mortality. Conclusion: Malaria was an uncommon cause of adult sepsis in a regional referral hospital in south-western Uganda. In this setting, a thorough evaluation for alternate causes of disease in patients presenting with sepsis is recommended. C1 [Auma, Mary A.; Mwanga-Amumpaire, Juliet; Muhindo, Rose; Wilson, L. Anthony; Il, Yap Boum] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. [Siedner, Mark J.] Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, Boston, MA USA. [Nyehangane, Dan; Nalusaji, Aisha; Mwanga-Amumpaire, Juliet; Il, Yap Boum] Epictr Mbarara Res Base, Mbarara, Uganda. [Nakaye, Martha] Mbarara Univ Sci & Technol, Dept Microbiol, Mbarara, Uganda. [Moore, Christopher C.] Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22903 USA. RP Moore, CC (reprint author), Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22903 USA. EM ccm5u@virginia.edu FU Pfizer Initiative in International Health; Center for Global Health at the University of Virginia; Lacor Hospital administration, Gulu, Uganda; Harvard Institute for Global Health; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; National Institutes of Health [T32 AI007433] FX Funding for the study was provided to MAA and CCM by the Pfizer Initiative in International Health and the Center for Global Health at the University of Virginia. This initiative was conceived to fund global infectious disease research and exchange programmes between post-doctoral fellows and students from the University of Virginia and several international partners to conduct research on global health issues. The major purpose of this programme is to foster and enhance bidirectional research training. An independent board at the University of Virginia determines the research proposals that are funded. Pfizer, Inc provided funds to promote the initiative but has no role in the planning or execution of research protocols, including the study described in this article. MAA also received salary, tuition, and research support from the Lacor Hospital administration, Gulu, Uganda. MS received salary and research support from the Harvard Institute for Global Health, the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988), and the National Institutes of Health (T32 AI007433). NR 28 TC 5 Z9 5 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAY 1 PY 2013 VL 12 AR 146 DI 10.1186/1475-2875-12-146 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 144YN UT WOS:000318979000001 PM 23634654 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Ian Wilmut-Pioneer of Cloning SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 NR 0 TC 0 Z9 0 U1 0 U2 3 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 MAY PY 2013 VL 88 IS 5 BP E41 EP E41 DI 10.1016/j.mayocp.2012.01.028 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 145BY UT WOS:000318989700001 PM 23639503 ER PT J AU Papisov, MI Belov, VV Gannon, KS AF Papisov, Mikhail I. Belov, Vasily V. Gannon, Kimberley S. TI Physiology of the Intrathecal Bolus: The Leptomeningeal Route for Macromolecule and Particle Delivery to CNS SO MOLECULAR PHARMACEUTICS LA English DT Review DE CNS; intrathecal; leptomeningeal; cerebrospinal fluid; CSF; drug delivery; biopharmaceuticals; proteins; bacteriophage; drug carriers; imaging ID ENZYME REPLACEMENT THERAPY; VIRCHOW-ROBIN SPACES; CONVECTION-ENHANCED DELIVERY; CENTRAL-NERVOUS-SYSTEM; GROWTH FACTOR-II/MANNOSE-6-PHOSPHATE RECEPTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; LYSOSOMAL STORAGE DISEASES; CEREBROSPINAL-FLUID FLOW; TRAUMATIC BRAIN-INJURY; DORSAL-ROOT GANGLIA AB Presently, there are no effective treatments for several diseases involving the CNS, which is protected by the bloo-brain, blood-CSF, and blood-arachnoid barriers. Traversing any of these barriers is difficult, especially for macromolecular drugs and particulates. However, there is significant experimental evidence that large molecules can be delivered to the CNS through the cerebrospinal fluid (CSF). The flux of the interstitial fluid in the CNS parenchyma, as well as the macro flux of CSF in the leptomeningeal space, are believed to be generally opposite to the desirable direction of CNS-targeted drug delivery. On the other hand, the available data suggest that the layer of pia mater lining the CNS surface is not continuous, and the continuity of the leptomeningeal space (LMS) with the perivascular spaces penetrating into the parenchyma provides an unexplored avenue for drug transport deep into the brain via CSF. The published data generally do not support the view that macromolecule transport from the LMS to CNS is hindered by the interstitial and CSF fluxes. The data strongly suggest that leptomeningeal transport depends on the location and volume of the administered bolus and consists of four processes: (i) pulsation-assisted convectional transport of the solutes with CSF, (ii) active "pumping" of CSF into the periarterial spaces, (iii) solute transport from the latter to and within the parenchyma, and (iv) neuronal uptake and axonal transport. The final outcome will depend on the drug molecule behavior in each of these processes, which have not been studied systematically. The data available to date suggest that many macromolecules and nanoparticles can be delivered to CNS in biologically significant amounts (>1% of the administered dose); mechanistic investigation of macromolecule and particle behavior in CSF may result in a significantly more efficient leptomeningeal drug delivery than previously thought. C1 [Papisov, Mikhail I.; Belov, Vasily V.] Shriners Hosp Children, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Papisov, Mikhail I.; Belov, Vasily V.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gannon, Kimberley S.] NeuroPhage Pharmaceut Inc, Cambridge, MA 02142 USA. RP Papisov, MI (reprint author), Shriners Hosp Children, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu OI Papisov, Mikhail/0000-0003-4716-2122 FU NIH [R21 CA152384]; DoD [BC100684] FX Authors thank Drs. P. Calias, R. Penn, M. Heartlein, T. McCauley, A.J. Fischman, and R. Fisher for valuable discussions, and E. Papisov for assistance with editing the manuscript. Previously unpublished data were from studies supported by NIH Grant R21 CA152384 and DoD Grant BC100684. NR 144 TC 15 Z9 15 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAY PY 2013 VL 10 IS 5 BP 1522 EP 1532 DI 10.1021/mp300474m PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 140QI UT WOS:000318669600006 PM 23316936 ER PT J AU Valencia, PM Pridgen, EM Perea, B Gadde, S Sweeney, C Kantoff, PW Bander, NH Lippard, SJ Langer, R Karnik, R Farokhzad, OC AF Valencia, Pedro M. Pridgen, Eric M. Perea, Brian Gadde, Suresh Sweeney, Christopher Kantoff, Philip W. Bander, Neil H. Lippard, Stephen J. Langer, Robert Karnik, Rohit Farokhzad, Omid C. TI Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles SO NANOMEDICINE LA English DT Article DE cisplatin; combination chemotherapy; irinotecan; nanoparticle; PSMA ID PLGA-PEG NANOPARTICLES; PROSTATE-CANCER; MEMBRANE ANTIGEN; IN-VIVO; COMBINATIONS; THERAPY; DELIVERY; PLATFORM; PERSPECTIVES; CHEMOTHERAPY AB Aim: Two unexplored aspects for irinotecan and cisplatin (I&C)combination chemotherapy are: actively targeting both drugs to a specific diseased cell type, and delivering both drugs on the same vehicle to ensure their synchronized entry into the cell at a well-defined ratio. In this work, the authors report the use of targeted polymeric nanoparticles (NPs) to coencapsulate and deliver I&C to cancer cells expressing the prostate-specific membrane antigen. Materials & methods: Targeted NPs were prepared in a single step by mixing four different precursors inside microfluidic devices. Results: I&C were encapsulated in 55-nm NPs and showed an eightfold increase in internalization by prostate-specific membrane antigen-expressing LNCaP cells compared with nontargeted NPs. NPs coencapsulating both drugs exhibited strong synergism in LNCaP cells with a combination index of 0.2. Conclusion: The strategy of coencapsulating both I&C in a single NP targeted to a specific cell type could potentially be used to treat different types of cancer. C1 [Valencia, Pedro M.; Pridgen, Eric M.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Perea, Brian] Arizona State Univ, Sch Engn Matter Transport & Energy, Tempe, AZ 85287 USA. [Gadde, Suresh; Farokhzad, Omid C.] Harvard Univ, Sch Med, Lab Nanomed & Biomat, Brigham & Womens Hosp, Boston, MA 02115 USA. [Gadde, Suresh; Farokhzad, Omid C.] Harvard Univ, Sch Med, Dept Anesthesiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Sweeney, Christopher; Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Bander, Neil H.] Cornell Univ, Weill Med Coll, New York, NY 10065 USA. [Lippard, Stephen J.; Langer, Robert] MIT, Dept Chem, Cambridge, MA 02139 USA. [Lippard, Stephen J.; Farokhzad, Omid C.] MIT, MIT Harvard Ctr Canc Nanotechnol Excellence, Cambridge, MA 02139 USA. [Karnik, Rohit] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Farokhzad, OC (reprint author), Harvard Univ, Sch Med, Lab Nanomed & Biomat, Brigham & Womens Hosp, Boston, MA 02115 USA. EM ofarokhzad@zeus.bwh.harvard.edu RI Gadde, Suresh/B-9483-2012; OI Gadde, Suresh/0000-0001-9102-3029; Perea, Brian/0000-0002-6805-2304 FU Koch-Prostate Cancer Foundation Award in Nanotherapeutics; NCI Center of Cancer Nanotechnology Excellence at MIT-Harvard [U54-CA151884]; NSF graduate research fellowship; NDSEG graduate research fellowship FX OC Farokhzad and R Langer have financial interests in BIND Biosciences and Selecta Biosciences. OC Farohkzad, R Langer and SJ Lippard have financial interests in Blend Therapeutics. This research was supported by the Koch-Prostate Cancer Foundation Award in Nanotherapeutics (R Langer and OC Farokhzad) and by the NCI Center of Cancer Nanotechnology Excellence at MIT-Harvard (U54-CA151884). PM Valencia is supported by NSF graduate research fellowship. EM Pridgen is supported by a NDSEG graduate research fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 35 TC 25 Z9 25 U1 7 U2 87 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PD MAY PY 2013 VL 8 IS 5 BP 687 EP 698 DI 10.2217/NNM.12.134 PG 12 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 143FL UT WOS:000318852100008 PM 23075285 ER PT J AU Sperandio, FF Sharma, SK Wang, M Jeon, S Huang, YY Dai, TH Nayka, S de Sousa, SCOM Chiang, LY Hamblin, MR AF Sperandio, Felipe F. Sharma, Sulbha K. Wang, Min Jeon, Seaho Huang, Ying-Ying Dai, Tianhong Nayka, Suhasini de Sousa, Suzana C. O. M. Chiang, Long Y. Hamblin, Michael R. TI Photoinduced electron-transfer mechanisms for radical-enhanced photodynamic therapy mediated by water-soluble decacationic C-70 and C84O2 Fullerene Derivatives SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Photodynamic therapy; Decacationic [70] fullerene derivatives; Decacationic [84] fullerene-dioxide derivatives; Electron transfer; Ascorbic acid ID ENERGY-TRANSFER; SINGLET-OXYGEN; CANCER-CELLS; CHARGE-SEPARATION; PLASMA-MEMBRANE; IONIC LIQUIDS; ASCORBIC-ACID; C-60; TRANSPORT; KERATINOCYTES AB Fullerenes are promising candidates for photodynamic therapy (PDT). Thus, C-70 and novel C84O2 fullerenes were functionalized with and without an additional deca-tertiary ethyleneamino-chain as an electron source, giving rise to two distinct pairs of photosensitizers, the monoadducts LC-17, LC-19 and the bisadducts LC18 and LC-20 to perform PDT in HeLa cells with UVA, blue, green, white and red light. Shorter wavelengths gave more phototoxicity with LC-20 while LC-19 was better at longer wavelengths; the ratio between killing obtained with LC-19 and LC-20 showed an almost perfect linear correlation (R = 0.975) with wavelength. The incorporation of a deca-tertiary amine chain in the C84O2 fullerene gave more PDT killing when excited with shorter wavelengths or in the presence of low ascorbate concentration through higher generation of hydroxyl radicals. Photoactivated C84O2 fullerenes induced apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage demonstrated by acridine orange and rhodamine 123 fluorescent probes. (C) 2013 Elsevier Inc. All rights reserved. C1 [Sperandio, Felipe F.; de Sousa, Suzana C. O. M.] Univ Sao Paulo, Sch Dent, Dept Oral Pathol, BR-05508000 Sao Paulo, Brazil. [Sperandio, Felipe F.; Sharma, Sulbha K.; Huang, Ying-Ying; Dai, Tianhong; Nayka, Suhasini; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sperandio, Felipe F.; Huang, Ying-Ying; Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Sperandio, Felipe F.] Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil. [Wang, Min; Jeon, Seaho; Chiang, Long Y.] Univ Massachusetts, Dept Chem, Inst Nanosci & Engn Technol, Lowell, MA 01854 USA. [Chiang, Long Y.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Sousa, Suzana/H-6154-2012; OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01CA137108, RO1AI050875]; CAPES Foundation, Ministry of Education of Brazil [0310-11-5]; Airlift Research Foundation Extremity Trauma Research Grant [109421]; Basic Research Grant from the Orthopaedic Trauma Association [2012-16] FX This work was supported by NIH grant R01CA137108 to LYC. FFS was supported by CAPES Foundation, Ministry of Education of Brazil, grant number 0310-11-5. TD was supported by an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421) and a Basic Research Grant from the Orthopaedic Trauma Association (grant 2012-16). MRH was supported by NIH grant RO1AI050875. NR 51 TC 15 Z9 15 U1 1 U2 62 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD MAY PY 2013 VL 9 IS 4 BP 570 EP 579 DI 10.1016/j.nano.2012.09.005 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 145AS UT WOS:000318985600015 PM 23117043 ER PT J AU Lieber, DS Calvo, SE Shanahan, K Slate, NG Liu, ST Hershman, SG Gold, NB Chapman, BA Thorburn, DR Berry, GT Schmahmann, JD Borowsky, ML Mueller, DM Sims, KB Mootha, VK AF Lieber, Daniel S. Calvo, Sarah E. Shanahan, Kristy Slate, Nancy G. Liu, Shangtao Hershman, Steven G. Gold, Nina B. Chapman, Brad A. Thorburn, David R. Berry, Gerard T. Schmahmann, Jeremy D. Borowsky, Mark L. Mueller, David M. Sims, Katherine B. Mootha, Vamsi K. TI Targeted exome sequencing of suspected mitochondrial disorders SO NEUROLOGY LA English DT Article ID COMPLEX I DEFICIENCY; RESPIRATORY-CHAIN DISORDERS; WOLFRAM-SYNDROME; ATP SYNTHASE; MUTATIONS; DISEASE; PATIENT; GENE; DNA; HETEROZYGOSITY AB Objective: To evaluate the utility of targeted exome sequencing for the molecular diagnosis of mitochondrial disorders, which exhibit marked phenotypic and genetic heterogeneity. Methods: We considered a diverse set of 102 patients with suspected mitochondrial disorders based on clinical, biochemical, and/or molecular findings, and whose disease ranged from mild to severe, with varying age at onset. We sequenced the mitochondrial genome (mtDNA) and the exons of 1,598 nuclear-encoded genes implicated in mitochondrial biology, mitochondrial disease, or monogenic disorders with phenotypic overlap. We prioritized variants likely to underlie disease and established molecular diagnoses in accordance with current clinical genetic guidelines. Results: Targeted exome sequencing yielded molecular diagnoses in established disease loci in 22% of cases, including 17 of 18 (94%) with prior molecular diagnoses and 5 of 84 (6%) without. The 5 new diagnoses implicated 2 genes associated with canonical mitochondrial disorders (NDUFV1, POLG2), and 3 genes known to underlie other neurologic disorders (DPYD, KARS, WFS1), underscoring the phenotypic and biochemical overlap with other inborn errors. We prioritized variants in an additional 26 patients, including recessive, X-linked, and mtDNA variants that were enriched 2-fold over background and await further support of pathogenicity. In one case, we modeled patient mutations in yeast to provide evidence that recessive mutations in ATP5A1 can underlie combined respiratory chain deficiency. Conclusion: The results demonstrate that targeted exome sequencing is an effective alternative to the sequential testing of mtDNA and individual nuclear genes as part of the investigation of mitochondrial disease. Our study underscores the ongoing challenge of variant interpretation in the clinical setting. Neurology (R) 2013;80:1762-1770 C1 [Lieber, Daniel S.; Calvo, Sarah E.; Slate, Nancy G.; Liu, Shangtao; Hershman, Steven G.; Gold, Nina B.; Chapman, Brad A.; Borowsky, Mark L.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Slate, Nancy G.; Liu, Shangtao; Hershman, Steven G.; Gold, Nina B.; Sims, Katherine B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lieber, Daniel S.; Calvo, Sarah E.; Hershman, Steven G.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Lieber, Daniel S.; Calvo, Sarah E.; Hershman, Steven G.; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Shanahan, Kristy; Mueller, David M.] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Biochem & Mol Biol, Chicago, IL USA. [Thorburn, David R.] Univ Melbourne, Murdoch Childrens Res Inst, Royal Childrens Hosp, Melbourne, Vic 3010, Australia. [Thorburn, David R.] Univ Melbourne, Dept Paediat, Melbourne, Vic 3010, Australia. [Berry, Gerard T.] Harvard Univ, Sch Med, Manton Ctr Orphan Dis Res, Childrens Hosp Boston, Boston, MA USA. [Schmahmann, Jeremy D.; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schmahmann, Jeremy D.; Sims, Katherine B.] Harvard Univ, Sch Med, Boston, MA USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu RI Thorburn, David/G-6266-2013; OI Hershman, Steven/0000-0001-9167-7380; Berry, Gerard/0000-0001-5299-3313; thorburn, david/0000-0002-7725-9470 FU NSF; NIH [R01GM66223]; American Recovery and Reinvestment Act (ARRA) funds from the National Human Genome Research Institute, NIH [RC2HG005556] FX This work was supported by an NSF Graduate Research Fellowship Program grant (D. S. L.), a grant from NIH R01GM66223 (D. M. M.), and American Recovery and Reinvestment Act (ARRA) funds through grant number RC2HG005556 (V. K. M.) from the National Human Genome Research Institute, NIH. NR 39 TC 45 Z9 50 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY PY 2013 VL 80 IS 19 BP 1762 EP 1770 DI 10.1212/WNL.0b013e3182918c40 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 141BL UT WOS:000318700300034 PM 23596069 ER PT J AU Lin, BK Edelman, E McInerney, JD O'Leary, J Edelson, V Hughes, KS Drohan, B Kyler, P Lloyd-Puryear, M Scott, J Dolan, SM AF Lin, Bruce K. Edelman, Emily McInerney, Joseph D. O'Leary, James Edelson, Vaughn Hughes, Kevin S. Drohan, Brian Kyler, Penny Lloyd-Puryear, Michele Scott, Joan Dolan, Siobhan M. TI Personalizing prenatal care using family health history: identifying a panel of conditions for a novel electronic genetic screening tool SO PERSONALIZED MEDICINE LA English DT Article DE clinical decision support; family health history; genetic screening; personalized risk assessment; prenatal care ID CYSTIC-FIBROSIS; RISK-ASSESSMENT; SURGEON-GENERALS; CLINICAL-USE; PREVENTION; GUIDELINES; INFORMATION; COLLECTION; PROVIDERS; STATEMENT AB In the age of genomic medicine, family health history (FHH) remains an important tool for personalized risk assessment as it can inform approaches to disease prevention and management. In primary care, including in prenatal settings, providers recognize that FHH enables them to assess the risk for birth defects and complex conditions that not only affect the fetus health, but also the mother's. However, many providers lack the time to gather FHH or the knowledge to confidently interpret the data. Electronic tools providing clinical decision support using FHH data can aid the busy provider with data collection and interpretation. We describe the scope of conditions included in a patient-entered FHH tool that provides clinical decision support and point-of-care education to assist with patient management. This report details how we selected the conditions for which it is appropriate to use FHH as a means to promote personalized medicine in primary prenatal care. C1 [Lin, Bruce K.; Dolan, Siobhan M.] March Dimes Fdn, White Plains, NY 10605 USA. [Edelman, Emily; McInerney, Joseph D.; Scott, Joan] Natl Coalit Hlth Profess Educ Genet, Lutherville Timonium, MD 21093 USA. [O'Leary, James; Edelson, Vaughn] Genet Alliance, Washington, DC 20008 USA. [Hughes, Kevin S.; Drohan, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kyler, Penny] Hlth Resources Serv Adm, Rockville, MD 20857 USA. RP Lin, BK (reprint author), March Dimes Fdn, 1275 Mamaroneck Ave, White Plains, NY 10605 USA. EM blin@marchofdimes.com OI Hughes, Kevin/0000-0003-4084-6484 FU Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau, Genetic Services Branch [U33MC12786] FX This project is supported by grant U33MC12786 from Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau, Genetic Services Branch. KS Hughes is the inventor of Hughes Risk Apps. The authors are affiliated with institutions, with the exception of HRSA, that may receive royalties from the licensing of the prenatal module discussed in the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 68 TC 3 Z9 3 U1 0 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAY PY 2013 VL 10 IS 3 BP 307 EP 318 DI 10.2217/PME.13.18 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 141LW UT WOS:000318727700014 ER PT J AU Milfred-LaForest, SK Chow, SL DiDomenico, RJ Dracup, K Ensor, CR Gattis-Stough, W Heywood, JT Lindenfeld, J Page, RL Patterson, JH Vardeny, O Massie, BM AF Milfred-LaForest, Sherry K. Chow, Sheryl L. DiDomenico, Robert J. Dracup, Kathleen Ensor, Christopher R. Gattis-Stough, Wendy Heywood, J. Thomas Lindenfeld, JoAnn Page, Robert L., II Patterson, J. Herbert Vardeny, Orly Massie, Barry M. TI Clinical Pharmacy Services in Heart Failure: An Opinion Paper from the Heart Failure Society of America and American College of Clinical Pharmacy Cardiology Practice and Research Network SO PHARMACOTHERAPY LA English DT Article DE heart failure; clinical pharmacist; multidisciplinary team; heart transplant ID UNITED-STATES HOSPITALS; ADVERSE DRUG-REACTIONS; INPATIENT MEDICATION RECONCILIATION; VENTRICULAR ASSIST DEVICE; PRESCRIBER ORDER ENTRY; INTENSIVE-CARE-UNIT; TRANSPLANT RECIPIENT; PHARMACEUTICAL CARE; MANAGEMENT PROGRAM; CARDIOVASCULAR-DISEASE AB Heart failure (HF) care takes place in multiple settings, with a variety of providers, and generally involves patients who have multiple comorbidities. This situation is a "perfect storm" of factors that predispose patients to medication errors. The goals of this paper are to outline potential roles for clinical pharmacists in a multidisciplinary HF team, to document outcomes associated with interventions by clinical pharmacists, to recommend minimum training for clinical pharmacists engaged in HF care, and to suggest financial strategies to support clinical pharmacy services within a multidisciplinary team. As patients transition from inpatient to outpatient settings and between multiple caregivers, pharmacists can positively affect medication reconciliation and education, assure consistency in management that results in improvements in patient satisfaction and medication adherence, and reduce medication errors. For mechanical circulatory support and heart transplant teams, the Centers for Medicare and Medicaid Services considers the participation of a transplant pharmacology expert (e. g., clinical pharmacist) to be a requirement for accreditation, given the highly specialized and complex drug regimens used. Although reports of outcomes from pharmacist interventions have been mixed owing to differences in study design, benefits such as increased use of evidence-based therapies, decreases in HF hospitalizations and emergency department visits, and decreases in all-cause read-missions have been demonstrated. Clinical pharmacists participating in HF or heart transplant teams should have completed specialized postdoctoral training in the form of residencies and/or fellowships in cardiovascular and/or transplant pharmacotherapy, and board certification is recommended. Financial mechanisms to support pharmacist participation in the HF teams are variable. Positive outcomes associated with clinical pharmacist activities support the value of making this resource available to HF teams. C1 [Milfred-LaForest, Sherry K.] Louis Stokes Cleveland VA Med Ctr, Dept Pharm, Cleveland, OH USA. [Chow, Sheryl L.] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA. [DiDomenico, Robert J.] Univ Illinois, Coll Pharm, Chicago, IL USA. [Dracup, Kathleen] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Ensor, Christopher R.] Univ Pittsburgh, Coll Pharm, Pittsburgh, PA USA. [Gattis-Stough, Wendy] Campbell Univ, Coll Pharm & Hlth Sci, Dept Clin Res, Buies Creek, NC 27506 USA. [Heywood, J. Thomas] Scripps Clin, Dept Med, La Jolla, CA 92037 USA. [Lindenfeld, JoAnn] Univ Colorado Denver, Heart Transplantat Program, Dept Med, Div Cardiol, Aurora, CO USA. [Page, Robert L., II] Univ Colorado Denver, Sch Pharm, Dept Med, Div Cardiol, Aurora, CO USA. [Page, Robert L., II] Univ Colorado Denver, Sch Med, Dept Med, Div Cardiol, Aurora, CO USA. [Patterson, J. Herbert] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA. [Vardeny, Orly] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Vardeny, Orly] Univ Wisconsin, Sch Med, Madison, WI USA. [Massie, Barry M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Chow, SL (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E 2nd St, Pomona, CA 91766 USA. EM schow@westernu.edu; barry.massie@va.gov OI DiDomenico, Robert/0000-0002-9374-8012 FU Medtronic; Gambro; St. Jude; Zensun; Otsuka; Novartis; Amgen FX Robert J. DiDomenico is a consultant for F. Hoffman LaRoche. J. Thomas Heywood has received speaking honoraria from Actelion, Medtronic, St Jude, and Thoratec; is a consultant for Actelion, Medtronic, and Thoratec; and has received research grants from Medtronic and Gambro and fellowship support from St. Jude. JoAnn Lindenfeld is a consultant for St Jude, Boston Scientific, and Abbott and has received a research grant from Zensun. J. Herbert Patterson has received speaking honoraria from Otsuka, is a consultant for Otsuka and Novartis, and has received research grants from Otsuka, Novartis, and Amgen. All of the other authors report no potential conflict of interest. NR 135 TC 11 Z9 11 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2013 VL 33 IS 5 BP 529 EP 548 DI 10.1002/phar.1295 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 137MB UT WOS:000318438900115 PM 23649813 ER PT J AU Pan, JD Bredella, MA AF Pan, Judong Bredella, Miriam A. TI Imaging of Soft Tissue Abnormalities About the Hip SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Hip; Joint capsule; Tendons; Plica; Capsule; Myotendinous strain; Ischiofemoral impingement ID QUADRATUS FEMORIS MUSCLE; PIGMENTED VILLONODULAR SYNOVITIS; INSERTION AVULSION SYNDROME; TROCHANTERIC-PAIN-SYNDROME; SNAPPING ILIOPSOAS TENDON; CAPSULAR LIGAMENTS; CLINICAL FINDINGS; ABDUCTOR TENDONS; MR ARTHROGRAPHY; DIAGNOSIS AB Soft tissue abnormalities about the hip represent a common clinical problem. Although the signs and symptoms of some of these abnormalities are clinically evident, other entities are frequently overlooked. This article provides an overview and discusses the role of major imaging modalities, especially MR imaging, the primary modality for evaluation of many soft-tissue abnormalities. An introduction to fundamental imaging anatomy and functional roles of soft tissue structures about the hip is provided, recognizing their importance in making the correct diagnosis. lntra-articular and extra-articular soft tissue abnormalities reviewed systematically according to their mechanism of injury and anatomic or functional compartments. C1 [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW-6E, Boston, MA 02114 USA. EM mbredella@partners.org NR 62 TC 1 Z9 1 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 2013 VL 51 IS 3 BP 353 EP + DI 10.1016/j.rcl.2012.10.003 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146IR UT WOS:000319085300003 PM 23622089 ER PT J AU Kapur, VK Wilsdon, AG Au, D Avdalovic, M Enright, P Fan, VS Hansel, NN Heckbert, SR Jiang, R Krishnan, JA Mukamal, K Yende, S Barr, RG AF Kapur, Vishesh K. Wilsdon, Anthony G. Au, David Avdalovic, Mark Enright, Paul Fan, Vincent S. Hansel, Nadia N. Heckbert, Susan R. Jiang, Rui Krishnan, Jerry A. Mukamal, Kenneth Yende, Sachin Barr, R. Graham TI Obesity Is Associated With a Lower Resting Oxygen Saturation in the Ambulatory Elderly: Results From the Cardiovascular Health Study SO RESPIRATORY CARE LA English DT Article DE pulse oximetry; oxygen; obesity; body mass index; waist circumference; hypoxemia; pulmonary function test ID OLDER-ADULTS AB BACKGROUND: The contribution of obesity to hypoxemia has not been reported in a community-based study. Our hypothesis was that increasing obesity would be independently associated with lower S-pO2 in an ambulatory elderly population. METHODS: The Cardiovascular Health Study ascertained resting S-pO2 in 2,252 subjects over age 64. We used multiple linear regression to estimate the association of body mass index (BMI) with S-pO2 and to adjust for potentially confounding factors. Covariates including age, sex, race, smoking, airway obstruction (based on spirometry), self reported diagnosis of emphysema, asthma, heart failure, and left ventricular function (by echocardiography) were evaluated. RESULTS: Among 2,252 subjects the mean and median S-pO2 were 97.6% and 98.0% respectively; 5% of subjects had S-pO2 values below 95%. BMI was negatively correlated with S-pO2 (Spearman R = -0.27, P < .001). The mean difference in S-pO2 between the lowest and highest BMI categories (< 25 kg/m(2) and >= 35 kg/m(2)) was 1.33% (95% CI 0.89-1.78%). In multivariable linear regression analysis, S-pO2 was significantly inversely associated with BMI (1.4% per 10 units of BMI, 95% CI 1.2-1.6, for whites/others, and 0.87% per 10 units of BMI, 95% CI 0.47-1.27, for African Americans). CONCLUSIONS: We found a narrow distribution of S-pO2 values in a community-based sample of ambulatory elderly. Obesity was a strong independent contributor to a low S-pO2 with effects comparable to or greater than other factors clinically associated with lower S-pO2. C1 [Kapur, Vishesh K.; Au, David; Fan, Vincent S.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Wilsdon, Anthony G.] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98104 USA. [Au, David; Fan, Vincent S.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. [Avdalovic, Mark] Univ Calif Davis, Sch Med, Div Pulm & Crit Care Med, Davis, CA 95616 USA. [Enright, Paul] Univ Arizona, Coll Med, Resp Sci Ctr, Tucson, AZ USA. [Hansel, Nadia N.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. [Jiang, Rui; Barr, R. Graham] Columbia Univ, Med Ctr, Dept Epidemiol, Dept Med, New York, NY USA. [Krishnan, Jerry A.] Univ Illinois Hosp & Hlth Sci Syst, Div Pulm Crit Care Sleep & Allergy, Chicago, IL USA. [Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness Ctr, Pittsburgh, PA USA. RP Kapur, VK (reprint author), Univ Washington, Div Pulm & Crit Care Med, Box 359803,325 9th Ave, Seattle, WA 98104 USA. RI Kapur, Vishesh/K-1054-2014 OI Kapur, Vishesh/0000-0002-5417-1097 FU National Institutes of Health [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]; National Heart, Lung, and Blood Institute [HL080295]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058] FX This research was partly supported by National Institutes of Health grants 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, National Heart, Lung, and Blood Institute grant HL080295, the National Institute of Neurological Disorders and Stroke, and National Institute on Aging grants AG-023629, AG-15928, AG-20098, and AG-027058. The Cardiovascular Health Study principal investigators and institutions are listed at http://www.chs-nhlbi.org/pi.htm. NR 14 TC 3 Z9 3 U1 0 U2 3 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2013 VL 58 IS 5 BP 831 EP 837 DI 10.4187/respcare.02008 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 141UA UT WOS:000318750800014 PM 23107018 ER PT J AU Myers, TR Bollig, SM Hess, DR AF Myers, Timothy R. Bollig, Suzanne M. Hess, Dean R. TI Respiratory Care Year in Review 2012: Asthma and Sleep-Disordered Breathing SO RESPIRATORY CARE LA English DT Review DE asthma; lung function; pharmacology; diabetes; sleep-disordered breathing; patient education ID EMERGENCY-DEPARTMENT VISIT; EXHALED NITRIC-OXIDE; INHALED CORTICOSTEROIDS; FOLLOW-UP; CONTROLLER MEDICATIONS; FENO MEASUREMENTS; CONTROLLED-TRIAL; CHILDREN; APNEA; MANAGEMENT AB Asthma has long been recognized as a common respiratory disease, and the recognition of sleep-disordered breathing is becoming more prevalent. Patients with these disorders are commonly seen by clinicians caring for patients with respiratory disease. There is also much academic interest in asthma and sleep-disordered breathing. The purpose of this paper is to review the recent literature related to asthma and sleep-disordered breathing in a manner that is most likely to have interest to the readers of RESPIRATORY CARE. C1 [Myers, Timothy R.] Amer Assoc Resp Care, Irving, TX USA. [Bollig, Suzanne M.] Hays Med Ctr, Sleep & Neurodiagnost Inst, Hays, KS USA. [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 51 TC 1 Z9 1 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2013 VL 58 IS 5 BP 874 EP 883 DI 10.4187/respcare.02481 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 141UA UT WOS:000318750800020 PM 23625896 ER PT J AU Schytz, HW Jensen, BE Jennum, P Selb, J Boas, DA Ashina, M AF Schytz, Henrik Winther Jensen, Benedicte Ersted Jennum, Poul Selb, Juliette Boas, David A. Ashina, Messoud TI Low-frequency oscillations and vasoreactivity of cortical vessels in obstructive sleep apnea during wakefulness: A near infrared spectroscopy study SO SLEEP MEDICINE LA English DT Article DE Obstructive sleep apnea; Continuous positive airway pressure; Cortical vessels; Cerebral autoregulation; Near infrared spectroscopy; Breath-holding tests; Autonomic nervous system; Stroke ID POSITIVE AIRWAY PRESSURE; CEREBRAL HEMODYNAMICS; CEREBROVASCULAR REACTIVITY; INTERMITTENT HYPOXIA; ADULTS; RISK; HYPERTENSION; MECHANISMS; HYPOPNEA; STROKE AB Objectives: Effective nasal continuous positive airway pressure (CPAP) therapy reduces the cardiovascular outcomes associated with obstructive sleep apnea (OSA), but the mechanism behind this effect is unclear. We investigated if OSA patients during wakefulness showed signs of increased sympathetic activity and decreased vasoreactivity in cerebral cortical vessels as measured with near-infrared spectroscopy (NIRS), and if this may be reversed by CPAP treatment. Subjects and methods: 23 OSA patients (mean age, 55 y) naive to CPAP were included in a prospective interventional study. The OSA patients received CPAP therapy for at least two months. Cortical low-frequency oscillation (LFO) amplitudes and vasoreactivity during a breath hold test were measured with NIRS and were compared between baseline and after CPAP treatment. Baseline values also were compared to 13 healthy controls (mean age, 52 y). Results: We found a decrease in LFO amplitudes after CPAP therapy (P = 0.022) in OSA patients. We found no differences in LFO amplitudes between OSA patients and healthy controls (P = 0.934). There were no differences in peak vascular response following breath hold tests in OSA patients before and after CPAP therapy (P = 0.158) or compared to healthy controls (P = 0.740). Conclusion: Our NIRS study revealed a decrease in LFO amplitude following two months of CPAP treatment in OSA patients, which may reflect a decrease in sympathetic activity affecting cortical vessels. (c) 2013 Elsevier B.V. All rights reserved. C1 [Schytz, Henrik Winther; Jensen, Benedicte Ersted; Ashina, Messoud] Glostrup Univ Hosp, Danish Headache Ctr, Glostrup, Denmark. [Schytz, Henrik Winther; Jensen, Benedicte Ersted; Ashina, Messoud] Glostrup Univ Hosp, Dept Neurol, Glostrup, Denmark. [Schytz, Henrik Winther; Jensen, Benedicte Ersted; Jennum, Poul] Glostrup Univ Hosp, Danish Ctr Sleep Med, Glostrup, Denmark. [Selb, Juliette; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Opt Div,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Ashina, M (reprint author), Glostrup Cty Hosp, Danish Headache Ctr, Nordre Ringvej 57, DK-2600 Glostrup, Copenhagen, Denmark. EM ashina@dadlnet.dk OI Schytz, Henrik Winther/0000-0002-6262-2986 FU Lundbeck Foundation via the Lundbeck Foundation Center for Neurovascular Signaling (LUCENS); Gangsted Foundation; Frimodt-Heineke Foundation; Toyota Foundation; Augustinus Foundation FX The authors wish to thank lab technicians, Winnie Gronning Nielsen and Lene Elkjaer, for their excellent and dedicated assistance. The study was supported by the Lundbeck Foundation via the Lundbeck Foundation Center for Neurovascular Signaling (LUCENS), the Gangsted Foundation, the Frimodt-Heineke Foundation, the Toyota Foundation and the Augustinus Foundation. NR 38 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD MAY PY 2013 VL 14 IS 5 BP 416 EP 421 DI 10.1016/j.sleep.2012.12.009 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 139VC UT WOS:000318612100006 PM 23517585 ER PT J AU Pena, JR Saidman, S Major, E Hague, TJ Berces, A AF Pena, Jeremy R. Saidman, Susan Major, Endre Hague, Tim J. Berces, Attila TI HLA TYPING IN THE CLINICAL LABORATORY USING NEXT GENERATION SEQUENCING SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 27th Annual EFI European Immunogenetics and Histocompatibility Conference CY MAY 11-14, 2013 CL Maastricht, NETHERLANDS SP EFI C1 [Pena, Jeremy R.; Saidman, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Major, Endre; Hague, Tim J.; Berces, Attila] Omixon, Budapest, Hungary. EM attila.berces@omixon.com 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 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 2013 VL 81 IS 5 BP 350 EP 350 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 138QN UT WOS:000318523600210 ER PT J AU Gao, C Kong, NR Li, AL Tatetu, H Ueno, S Yang, YY He, J Yang, JC Ma, YP Kao, GS Tenen, DG Chai, L AF Gao, Chong Kong, Nikki R. Li, Ailing Tatetu, Hiro Ueno, Shikiko Yang, Youyang He, Jie Yang, Jianchang Ma, Yupo Kao, Grace S. Tenen, Daniel G. Chai, Li TI SALL4 is a key transcription regulator in normal human hematopoiesis SO TRANSFUSION LA English DT Article ID EARLY EMBRYONIC-DEVELOPMENT; ENHANCED SELF-RENEWAL; CD34+ MARROW-CELLS; STEM-CELLS; OKIHIRO-SYNDROME; DROSOPHILA EMBRYO; LEUKEMIC-CELLS; HOMEOTIC GENE; MUTATIONS; BMI-1 AB BACKGROUND: Stem cell factor SALL4 is a zinc finger transcription factor. It plays vital roles in the maintenance of embryonic stem cell properties, functions as an oncogene in leukemia, and has been recently proposed to use for cord blood expansion. The mechanism(s) by which SALL4 functions in normal human hematopoiesis, including identification of its target genes, still need to be explored. STUDY DESIGN AND METHODS: Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) was used for mapping SALL4 global gene targets in normal primary CD34+ cells. The results were then correlated with SALL4 functional studies in the CD34+ cells. RESULTS: More than 1000 potential SALL4 downstream target genes have been identified, and validation of binding by ChIP-quantitative polymerase chain reaction was performed for 5% of potential targets. These include genes that are involving in hematopoietic differentiation and self-renewal, such as HOXA9, RUNX1, CD34, and PTEN. Down regulation of SALL4 expression using small-hairpin RNA in these cells led to decreased in vitro myeloid colonyforming abilities and impaired in vivo engraftment. Furthermore, HOXA9 was identified to be a major SALL4 target in normal human hematopoiesis and the loss of either SALL4 or HOXA9 expression in CD34+ cells shared a similar phenotype. CONCLUSION: Taken together, SALL4 is a key regulator in normal human hematopoiesis and the mechanism of its function is at least in part through the HOXA9. Future study will determine whether modulating the SALL4/HOXA9 pathway can be used in cellular therapy such as cord blood expansion and/or myeloid engraftment. C1 [Chai, Li] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Joint Program Transfus Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Program Transfus Med,Dept Med Oncol, Boston, MA 02115 USA. Nevada Canc Inst, Div Lab Med, Las Vegas, NV USA. Natl Univ Singapore, Ctr Translat Med, Canc Sci Inst Singapore, Singapore 117548, Singapore. Harvard Stem Cell Inst, Ctr Life Sci, Boston, MA USA. RP Chai, L (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Joint Program Transfus Med, 77 Ave Louis Pasteur,NRB652, Boston, MA 02115 USA. EM lchai@partners.org OI Tenen, Daniel/0000-0002-6423-3888 FU [RO1HL092437]; [PO1HL095489]; [DK080665] FX This work was supported in part through RO1HL092437 and PO1HL095489 (to LC) and DK080665 (to DGT). NR 32 TC 13 Z9 13 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2013 VL 53 IS 5 BP 1037 EP 1049 DI 10.1111/j.1537-2995.2012.03888.x PG 13 WC Hematology SC Hematology GA 140MC UT WOS:000318657200016 PM 22934838 ER PT J AU Channick, RN Delcroix, M Galie, N Ghofrani, HA Hunsche, E Jansa, P Le Brun, FO Mehta, S Mittelholzer, C Perchenet, L Pulido, T Sastry, B Sitbon, O Souza, R Torbicki, A Rubin, LJ Simonneau, G AF Channick, R. N. Delcroix, M. Galie, N. Ghofrani, H. A. Hunsche, E. Jansa, P. Le Brun, F. O. Mehta, S. Mittelholzer, C. Perchenet, L. Pulido, T. Sastry, B. Sitbon, O. Souza, R. Torbicki, A. Rubin, L. J. Simonneau, G. TI REDUCTION OF PULMONARY ARTERIAL HYPERTENSION (PAH)-RELATED HOSPITALIZATIONS WITH MACITENTAN IN THE RANDOMIZED CONTROLLED TRIAL SERAPHIN SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delcroix, M.] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Galie, N.] Univ Bologna, Bologna, Italy. [Ghofrani, H. A.] Univ Hosp Giessen, Giessen, Germany. [Hunsche, E.; Le Brun, F. O.; Mittelholzer, C.; Perchenet, L.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Jansa, P.] Charles Univ Prague, Prague, Czech Republic. [Mehta, S.] Western Univ, Victoria Hosp, London Hlth Sci Ctr, London, ON, Canada. [Pulido, T.] Natl Heart Inst, Mexico City, DF, Mexico. [Sastry, B.] CARE Hosp, Hyderabad, Andhra Pradesh, India. [Sitbon, O.; Simonneau, G.] Univ Paris 11, Hop Univ Bicetre, Le Kremlin Bicetre, France. [Souza, R.] Univ Sao Paulo, Sch Med, Heart Inst, Sao Paulo, Brazil. [Torbicki, A.] ECZ Otwock, Ctr Postgrad Med Educ, Otwock, Poland. [Rubin, L. J.] Univ Calif San Diego, La Jolla, CA 92093 USA. RI Souza, Rogerio/I-3584-2013 NR 0 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2013 VL 16 IS 3 BP A231 EP A231 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 144CE UT WOS:000318916402151 ER PT J AU Fonda, JR McGlinchey, RE Milberg, WP Rudolph, JL Hunt, PR Reynolds, MW Yonan, C AF Fonda, J. R. McGlinchey, R. E. Milberg, W. P. Rudolph, J. L. Hunt, P. R. Reynolds, M. W. Yonan, C. TI STUDY OF PSEUDOBULBAR AFFECT SYMPTOMS IN VETERANS WITH MILD TRAUMATIC BRAIN INJURY SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Fonda, J. R.; McGlinchey, R. E.; Milberg, W. P.; Rudolph, J. L.] VA Boston Healthcare Syst, Boston, MA USA. [Hunt, P. R.; Reynolds, M. W.] United BioSource Corp Inc, Lexington, MA USA. [Yonan, C.] Avanir Pharmaceut Inc, Grass Valley, CA 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2013 VL 16 IS 3 BP A103 EP A103 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 144CE UT WOS:000318916401032 ER PT J AU Frei, CR Juday, TR Jones, X Labreche, MJ Koeller, JM Hebden, T Seekins, DW Oramasionwu, CU Bollinger, M Copeland, LA Teshome, B Mortensen, EM AF Frei, C. R. Juday, T. R. Jones, X. Labreche, M. J. Koeller, J. M. Hebden, T. Seekins, D. W. Oramasionwu, C. U. Bollinger, M. Copeland, L. A. Teshome, B. Mortensen, E. M. TI COMPARATIVE VALUE OF FOUR MEASURES OF RETENTION IN EXPERT CARE IN PREDICTING CLINICAL OUTCOMES AND HEALTH CARE UTILIZATION IN HIV PATIENTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Frei, C. R.; Koeller, J. M.; Teshome, B.] Univ Texas Austin, San Antonio, TX USA. [Frei, C. R.; Koeller, J. M.; Teshome, B.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Juday, T. R.; Hebden, T.; Seekins, D. W.] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Jones, X.; Bollinger, M.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, VERDICT Res Program, San Antonio, TX USA. [Labreche, M. J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Oramasionwu, C. U.] Univ N Carolina, Chapel Hill, NC USA. [Copeland, L. A.] Scott & White Healthcare, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Mortensen, E. M.] VA North Texas Hlth Care Syst, Dallas, TX 75390 USA. [Mortensen, E. M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2013 VL 16 IS 3 BP A184 EP A185 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 144CE UT WOS:000318916401455 ER PT J AU Sansgiry, S Naik, AD Brown, AC Latini, DM AF Sansgiry, S. Naik, A. D. Brown, A. C. Latini, D. M. TI QUALITY OF LIFE AMONG DIABETES PATIENTS SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Sansgiry, S.; Naik, A. D.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Brown, A. C.] Michael E DeBakey VA Med Ctr, VA HSR&D Ctr Excellence, Houston, TX USA. [Latini, D. M.] San Francisco VA Med Ctr, Baylor Coll Med, Scott Dept Urol, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2013 VL 16 IS 3 BP A196 EP A196 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 144CE UT WOS:000318916401515 ER PT J AU Tang, Y Gellad, WF Men, A Donohue, JM AF Tang, Y. Gellad, W. F. Men, A. Donohue, J. M. TI REGIONAL VARIATION IN USE OF GENERIC DRUGS AND MEDICARE PRESCRIPTION DRUG COST SHARING SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Tang, Y.; Gellad, W. F.; Men, A.; Donohue, J. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Gellad, W. F.] RAND, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2013 VL 16 IS 3 BP A248 EP A248 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 144CE UT WOS:000318916402243 ER PT J AU Potenza, MN Brody, AL AF Potenza, Marc N. Brody, Arthur L. TI Commentary on Boileau etal. (2013): Distinguishing D2/D3 dopaminergic contributions to addictions SO ADDICTION LA English DT Editorial Material DE [11C]-(+)-PHNO; [11C]-raclopride; addiction; D2; D3 dopamine; gambling; striatum ID POSITRON-EMISSION-TOMOGRAPHY; RECEPTOR; PET; IMPULSIVITY; RELEASE; PRE C1 [Potenza, Marc N.] Yale Univ, Sch Med, Dept Psychiat, Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA. [Potenza, Marc N.] Yale Univ, Sch Med, Dept Child Study, Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA. [Potenza, Marc N.] Yale Univ, Sch Med, Dept Neurobiol, Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA. [Brody, Arthur L.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90095 USA. RP Potenza, MN (reprint author), Yale Univ, Sch Med, Dept Psychiat, Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA. EM abrody@ucla.edu FU CSRD VA [I01 CX000412]; NIDA NIH HHS [P20 DA027844, R01 DA020872, R01 DA20872] NR 19 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 J9 ADDICTION JI Addiction PD MAY PY 2013 VL 108 IS 5 BP 964 EP 965 DI 10.1111/add.12119 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 127IK UT WOS:000317691600023 PM 23587083 ER PT J AU Yan, TJ Escarce, JJ Liang, LJ Longstreth, WT Merkin, SS Ovbiagele, B Vassar, SD Seeman, T Sarkisian, C Brown, AF AF Yan, Tingjian Escarce, Jose J. Liang, Li-Jung Longstreth, W. T., Jr. Merkin, Sharon Stein Ovbiagele, Bruce Vassar, Stefanie D. Seeman, Teresa Sarkisian, Catherine Brown, Arleen F. TI Exploring psychosocial pathways between neighbourhood characteristics and stroke in older adults: the cardiovascular health study SO AGE AND AGEING LA English DT Article DE neighbourhood; psychosocial factors; stroke; older adults ID SOCIAL-ISOLATION; ISCHEMIC-STROKE; SOCIOECONOMIC-STATUS; DEPRESSIVE SYMPTOMS; DISEASE; RISK; POPULATION; OUTCOMES; SUPPORT AB Objectives: to investigate whether psychosocial pathways mediate the association between neighbourhood socioeconomic disadvantage and stroke. Methods: prospective cohort study with a follow-up of 11.5 years. Setting: the Cardiovascular Health Study, a longitudinal population-based cohort study of older adults >= 65 years. Measurements: the primary outcome was adjudicated incident ischaemic stroke. Neighbourhood socioeconomic status (NSES) was measured using a composite of six census-tract variables. Psychosocial factors were assessed with standard measures for depression, social support and social networks. Results: of the 3,834 white participants with no prior stroke, 548 had an incident ischaemic stroke over the 11.5-year follow-up. Among whites, the incident stroke hazard ratio (HR) associated with living in the lowest relative to highest NSES quartile was 1.32 (95% CI = 1.01-1.73), in models adjusted for individual SES. Additional adjustment for psychosocial factors had a minimal effect on hazard of incident stroke (HR = 1.31, CI = 1.00-1.71). Associations between NSES and stroke incidence were not found among African-Americans (n = 785) in either partially or fully adjusted models. Conclusions: psychosocial factors played a minimal role in mediating the effect of NSES on stroke incidence among white older adults. C1 [Yan, Tingjian] Cedars Sinai Med Ctr, Dept Resource & Outcomes Management, Los Angeles, CA 90048 USA. [Escarce, Jose J.; Liang, Li-Jung; Brown, Arleen F.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Merkin, Sharon Stein; Seeman, Teresa; Sarkisian, Catherine] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Ovbiagele, Bruce] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Vassar, Stefanie D.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Sarkisian, Catherine] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Brown, AF (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. EM abrown@mednet.ucla.edu FU American Heart Association Pharmaceutical Roundtable -Spina Outcomes Research Center [0875135N, 0875133N, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; National Heart, Lung, and Blood Institute [U01 HL080295]; NIH/National Center for Advancing Clinical and Translational Science (NCATS)/UCLA Clinical and Translational Science Institute [UL1TR000124] FX This work was supported by the American Heart Association Pharmaceutical Roundtable -Spina Outcomes Research Center #0875135N and #0875133N as well as by contract numbers N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. A.F.B. was also supported by the NIH/National Center for Advancing Clinical and Translational Science (NCATS)/UCLA Clinical and Translational Science Institute, grant # UL1TR000124. NR 25 TC 3 Z9 3 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 EI 1468-2834 J9 AGE AGEING JI Age Ageing PD MAY PY 2013 VL 42 IS 3 BP 391 EP 397 DI 10.1093/ageing/afs179 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 139AE UT WOS:000318552800021 PM 23264005 ER PT J AU Tamez, H Andress, D Solomon, SD Thadhani, R AF Tamez, Hector Andress, Dennis Solomon, Scott D. Thadhani, Ravi TI Reply to "The role of fibroblast growth factor-23 in left atrial volume" SO AMERICAN HEART JOURNAL LA English DT Letter ID CHRONIC KIDNEY-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; FGF23; MORTALITY; THERAPY; TRIAL C1 [Tamez, Hector; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Andress, Dennis] Abbott Labs, Abbott Pk, IL 60064 USA. [Solomon, Scott D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Tamez, H (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu RI Solomon, Scott/I-5789-2013 FU NIDDK NIH HHS [K24 DK094872] NR 8 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2013 VL 165 IS 5 BP E23 EP E23 DI 10.1016/j.ahj.2013.02.023 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 141KL UT WOS:000318724000002 PM 23622924 ER PT J AU Sonnenberg, A Boardman, CR AF Sonnenberg, Amnon Boardman, Charles R. TI When Cure Becomes Worse Than the Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID IRRITABLE-BOWEL-SYNDROME; SURGERY C1 [Sonnenberg, Amnon; Boardman, Charles R.] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon; Boardman, Charles R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI ,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2013 VL 108 IS 5 BP 854 EP 855 DI 10.1038/ajg.2013.18 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 141FE UT WOS:000318710200029 PM 23644967 ER PT J AU Kabbani, D Weir, SK Berg, G Chien, GC Strymish, J Gupta, K AF Kabbani, Dima Weir, Susan K. Berg, Gretchen Chien, Gina C. Strymish, Judith Gupta, Kalpana TI Cohorting based on nasal methicillin-resistant Staphylococcus aureus status: An opportunity to share more than a room SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Staphylococcus aureus; Colonization; Extra-nasal; Roommates ID ACTIVE SURVEILLANCE CULTURES; APIC TASK-FORCE; LEGISLATIVE MANDATES; POSITION STATEMENT; JOINT SHEA; INFECTIONS; CARRIAGE; COLONIZATION; ENTEROCOCCI; STRAINS AB Background: Hospital roommates are cohorted with similarly colonized patients to decrease methicillin-resistant Staphylococcus aureus (MRSA) transmission risk. However, little is known about differences in S aureus nasal and extranasal carriage between hospital roommates who are in MRSA or non-MRSA designated rooms. Methods: Patients sharing hospital rooms were cultured for S aureus in the nose, throat, and other body sites. Differences in S aureus methicillin and mupirocin susceptibility and USA300 type were evaluated. Results: Eighty-two patients comprising 48 roommate pairs were studied. Among 6 roommate pairs in MRSA rooms, 3 (50%) had differences in carriage based on having methicillin-susceptible S aureus at an extranasal body site. In non-MRSA rooms, 19 (45%) roommate pairs had differences in S aureus carriage. Extranasal colonization was significantly associated with discordance between roommates, P < .001. Antibiotic exposure, ward type, and the duration of room sharing were not associated with discordance. Conclusion: Patients have almost a 50% chance of having differences in S aureus colonization compared with their hospital roommate, even in MRSA-designated rooms. Cohorting by MRSA status at the time of admission may not be as effective a control strategy as horizontal measures that do not rely on known colonization with S aureus or other pathogens. Copyright (c) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. C1 [Kabbani, Dima; Weir, Susan K.; Berg, Gretchen; Gupta, Kalpana] VA Boston HCS, Dept Med, Boston, MA USA. [Kabbani, Dima; Weir, Susan K.; Strymish, Judith; Gupta, Kalpana] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Chien, Gina C.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Strymish, Judith] Harvard Univ, Sch Med, Boston, MA USA. [Gupta, Kalpana] Natl Ctr Occupat Hlth & Infect Control COHIC, Off Publ Hlth, Dept Vet Affairs, Gainesville, FL USA. RP Gupta, K (reprint author), VA Boston HCS, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Kalpana.gupta@va.gov NR 16 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAY PY 2013 VL 41 IS 5 BP 401 EP 404 DI 10.1016/j.ajic.2012.10.015 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 139UU UT WOS:000318611200005 PM 23499508 ER PT J AU Evans, ME Kralovic, SM Simbartl, LA Obrosky, DS Hammond, MC Goldstein, B Evans, CT Roselle, GA Jain, R AF Evans, Martin E. Kralovic, Stephen M. Simbartl, Loretta A. Obrosky, D. Scott Hammond, Margaret C. Goldstein, Barry Evans, Charlesnika T. Roselle, Gary A. Jain, Rajiv TI Prevention of methicillin-resistant Staphylococcus aureus infections in spinal cord injury units SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE MRSA ID ACUTE REHABILITATION UNIT; COLONIZATION; VETERANS; EPIDEMIOLOGY; ORGANISMS AB Background: Methicillin-resistant Staphylococcus aureus (MRSA) health care-associated infections (HAIs) are a concern in the 22 acute care Veterans Affairs (VA) spinal cord injury units where patients with unique rehabilitation and medical needs and a high risk of infection are treated. Methods: A bundle was implemented in VA spinal cord injury units consisting of nasal surveillance for MRSA on admission/in-hospital transfer/discharge, contact precautions for patients colonized or infected with MRSA, an emphasis on hand hygiene, and an institutional culture change where infection control became everyone's responsibility. Results: From October 2007, through June 2011, there were 51,627 admissions/transfers/discharges and 816,254 patient-days of care in VA spinal cord injury units. The percentage of patients screened increased to >95.0%. The mean admission MRSA prevalence was 38.6% +/- 19.1%. Monthly HAI rates declined 81% from 1.217 per 1,000 patient-days to 0.237 per 1,000 patient-days (P < .001). Bloodstream infections declined by 100% (P = .002), skin and soft-tissue infections by 60% (P = .007), and urinary tract infections by 33% (P = .07). Conclusion: Universal surveillance, contact precautions, hand hygiene, and an institutional culture change was associated with significant declines in MRSA HAIs in a setting with a high prevalence of MRSA colonization and a high risk for infection. C1 [Evans, Martin E.] Vet Hlth Adm, Dept Vet Affairs, MRSA MDRO Program Off, Washington, DC USA. [Evans, Martin E.; Kralovic, Stephen M.; Simbartl, Loretta A.; Roselle, Gary A.] Vet Hlth Adm, Dept Vet Affairs, Natl Infect Dis Serv, Washington, DC USA. [Evans, Martin E.; Kralovic, Stephen M.; Simbartl, Loretta A.; Roselle, Gary A.; Jain, Rajiv] Vet Hlth Adm, Dept Vet Affairs, VA Cent Off, Washington, DC USA. [Evans, Martin E.] Lexington VA Med Ctr, Lexington, KY USA. [Evans, Martin E.] Univ Kentucky, Coll Med, Lexington, KY USA. [Kralovic, Stephen M.; Simbartl, Loretta A.; Roselle, Gary A.] Cincinnati VA Med Ctr, Cincinnati, OH USA. [Kralovic, Stephen M.; Roselle, Gary A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Obrosky, D. Scott] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hammond, Margaret C.; Goldstein, Barry] Vet Hlth Adm, Dept Vet Affairs, VA Cent Off, Spinal Cord Injury Disorders Serv, Washington, DC USA. [Hammond, Margaret C.; Goldstein, Barry] Vet Hlth Adm, Dept Vet Affairs, VA Cent Off, Spinal Cord Injury Disorders Serv, Seattle, WA USA. [Evans, Charlesnika T.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, VA Spinal Cord Injury Qual Enhancement Res Initia, Hines, IL 60141 USA. [Evans, Charlesnika T.] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. RP Evans, ME (reprint author), VHA MDRO Program, 11I-CDD,1101 Vet Dr, Lexington, KY 40502 USA. EM Martin.Evans@va.gov FU Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, Quality Enhancement Research Initiative [RRP 09-163] FX The authors thank Meredith Ambrose, MHA, and Kathleen J. Risa, MSN, CRNP, CIC, for coordinating rollout of the Initiative and collecting data along with providing MRSA education to all involved with the Veterans Health Administration MRSA Prevention Initiative; Marta L. Render, MD, and Ron W. Freyberg, MS, for managing the inpatient evaluation center; and the clinical staff of the Veterans Affairs spinal cord injury units, MRSA prevention coordinators, infection preventionists, infectious diseases specialists, and clinical laboratory personnel at each facility for their hard work and dedication toward improving the health care of America's veterans. This study was supported in part by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, Quality Enhancement Research Initiative (RRP 09-163). NR 14 TC 9 Z9 9 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAY PY 2013 VL 41 IS 5 BP 422 EP 426 DI 10.1016/j.ajic.2012.06.006 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 139UU UT WOS:000318611200009 PM 23149087 ER PT J AU Pennock, S Kim, D Mukai, S Kuhnle, M Chun, DW Matsubara, J Cui, J Ma, P Maberley, D Samad, A Van Geest, RJ Oberstein, SL Schlingemann, RO Kazlauskas, A AF Pennock, Steven Kim, David Mukai, Shizuo Kuhnle, Matthew Chun, Dal W. Matsubara, Joanne Cui, Jing Ma, Patrick Maberley, David Samad, Arif Van Geest, Robert J. Oberstein, Sarit L. Schlingemann, Reinier O. Kazlauskas, Andrius TI Ranibizumab Is a Potential Prophylaxis for Proliferative Vitreoretinopathy, a Nonangiogenic Blinding Disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-DETACHMENT; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; INTRAVITREAL BEVACIZUMAB; EPIRETINAL MEMBRANES; SIGNAL-TRANSDUCTION; EXPERIMENTAL-MODEL; FACTOR RECEPTOR; VITREOUS-HUMOR AB Proliferative vitreoretinopathy (PVR) exemplifies a disease that is difficult to predict, Lacks effective treatment options, and substantially reduces the quality of life of an individual. Surgery to correct a rhegmatogenous retinal detachment fails primarily because of PVR. Likely mediators of PVR are growth factors in vitreous, which stimulate cells within and behind the retina as an inevitable consequence of a breached retina. Three classes of growth factors [vascular endothelial growth factor A (VEGF-A), platelet-derived growth factors (PDGFs), and non-PDGFs (growth factors outside of the PDGF family)] are relevant to PVR pathogenesis because they act on PDGF receptor alpha, which is required for experimental PVR and is associated with this disease in humans. We discovered that ranibizumab (a clinically approved agent that neutralizes VEGF-A) reduced the bioactivity of vitreous from patients and experimental animals with PVR, and protected rabbits from developing disease. The apparent mechanism of ranibizumab action involved derepressing PDGFs, which, at the concentrations present in PVR vitreous, inhibited non-PDGF-mediated activation of PDGF receptor alpha. These predinical findings suggest that available approaches to neutralize VEGF-A are prophylactic for PVR, and that anti-VEGF-based therapies may be effective for managing more than angiogenesis- and edema-driven pathological conditions. C1 [Pennock, Steven; Kim, David; Mukai, Shizuo; Kazlauskas, Andrius] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Pennock, Steven; Kim, David; Mukai, Shizuo; Kazlauskas, Andrius] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Kuhnle, Matthew; Chun, Dal W.] Walter Reed Army Med Ctr, Dept Surg, Ophthalmol Serv, Washington, DC 20307 USA. [Matsubara, Joanne; Cui, Jing; Ma, Patrick; Maberley, David] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. [Samad, Arif] Dalhousie Univ, Dept Ophthalmol & Visual Sci, Halifax, NS, Canada. [Van Geest, Robert J.; Oberstein, Sarit L.; Schlingemann, Reinier O.] Univ Amsterdam, Acad Med Ctr, Med Retina Unit, NL-1105 AZ Amsterdam, Netherlands. [Van Geest, Robert J.; Oberstein, Sarit L.; Schlingemann, Reinier O.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Ocular Angiogenesis Grp, NL-1105 AZ Amsterdam, Netherlands. RP Kazlauskas, A (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst,Massachusetts Eye & Ear Inf, 20 Staniford St, Boston, MA 02114 USA. EM andrius_kazlauskas@meei.harvard.edu FU Department of Defense [WB1XWH-10-1-0392]; NIH [EY012509]; Canadian Institutes of Health Research (CIHR); Mukai Fund; CIHR [IAO 77736, MOP 97806]; Massachusetts Eye and Ear Infirmary (Boston) FX Supported by Department of Defense grant WB1XWH-10-1-0392 and NIH grant EY012509 (A.K.), a Canadian Institutes of Health Research (CIHR) fellowship (S.P.), Mukai Fund and Massachusetts Eye and Ear Infirmary (Boston) gifts (S.M.), and CIHR grants IAO 77736 and MOP 97806 (J.M. and J.C.). NR 62 TC 15 Z9 15 U1 0 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 MAY PY 2013 VL 182 IS 5 BP 1659 EP 1670 DI 10.1016/j.ajpath.2013.01.052 PG 12 WC Pathology SC Pathology GA 138TY UT WOS:000318534100021 PM 23582767 ER PT J AU Meyer, NJ Feng, R Li, MY Zhao, Y Sheu, CC Tejera, P Gallop, R Bellamy, S Rushefski, M Lanken, PN Aplenc, R O'Keefe, GE Wurfel, MM Christiani, DC Christie, JD AF Meyer, Nuala J. Feng, Rui Li, Mingyao Zhao, Yang Sheu, Chau-Chyun Tejera, Paula Gallop, Robert Bellamy, Scarlett Rushefski, Melanie Lanken, Paul N. Aplenc, Richard O'Keefe, Grant E. Wurfel, Mark M. Christiani, David C. Christie, Jason D. TI IL1RN Coding Variant Is Associated with Lower Risk of Acute Respiratory Distress Syndrome and Increased Plasma IL-1 Receptor Antagonist SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE functional genetic polymorphism; acute lung injury; acute respiratory distress syndrome; IL-1 receptor antagonist; replication ID ACUTE LUNG INJURY; GENOME-WIDE ASSOCIATION; CHAIN-KINASE GENE; CONSENSUS CONFERENCE; ALLELE FREQUENCIES; ORGAN FAILURE; SEVERE SEPSIS; GENOTYPE DATA; INTERLEUKIN-1; POLYMORPHISM AB Rationale: Acute respiratory distress syndrome (ARDS) behaves as a complex genetic trait, yet knowledge of genetic susceptibility factors remains incomplete. Objectives: To identify genetic risk variants for ARDS using large scale genotyping. Methods: A multistage genetic association study was conducted of three critically ill populations phenotyped for ARDS. Stage I, a trauma cohort study (n=224), was genotyped with a 50K gene-centric single-nucleotide polymorphism (SNP) array. We tested SNPs associated with ARDS at P<5 x 10(-4) for replication in stage II, a trauma case-control population (n=778). SNPs replicating their association in stage II (P<0.005) were tested in a stage III nested case-control population of mixed subjects in the intensive care unit (n=2,063). Logistic regression was used to adjust for potential clinical confounders. We performed ELISA to test for an association between ARDS-associated genotype and plasma protein levels. Measurements and Main Results: A total of 12 SNPs met the stage I threshold for an association with ARDS. rs315952 in the IL1RN gene encoding IL-1 receptor antagonist (IL1RA) replicated its association with reduced ARDS risk in stages II (P<0.004) and III (P<0.02), and was robust to clinical adjustment (combined odds ratio=0.81; P=4.2 X 10(-5)). Plasma IL1RA level was associated with rs315952C in a subset of critically ill subjects. The effect of rs315952 was independent from the tandem repeat variant in IL1RN. Conclusions: The IL1RN SNP rs315952C is associated with decreased, risk of ARDS in three populations with heterogeneous ARDS risk factors, and with increased plasma IL1RA response. IL1RA may attenuate ARDS risk. C1 [Meyer, Nuala J.; Lanken, Paul N.; Christie, Jason D.] Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Perelman Sch Med, Philadelphia, PA 19104 USA. [Feng, Rui; Li, Mingyao; Gallop, Robert; Bellamy, Scarlett; Aplenc, Richard; Christie, Jason D.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Zhao, Yang; Sheu, Chau-Chyun; Tejera, Paula; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Sheu, Chau-Chyun] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Div Pulm & Crit Care Med, Kaohsiung, Taiwan. [Rushefski, Melanie; Aplenc, Richard] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Div Oncol, Philadelphia, PA 19104 USA. [O'Keefe, Grant E.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Wurfel, Mark M.] Univ Washington, Harborview Med Ctr, Dept Pulm & Crit Care Med, Seattle, WA 98104 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Meyer, NJ (reprint author), Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Perelman Sch Med, 3600 Spruce St,8026 Maloney, Philadelphia, PA 19104 USA. EM nuala.meyer@uphs.upenn.edu FU National Institutes of Health (NIH); Hospital of the University of Pennsylvania [HL060290, HL079063]; Harborview [GM066946]; Massachusetts General Hospital [HL060710]; NIH [RC2HL101770, HL081619, HL090021, HL102254] FX Supported by National Institutes of Health (NIH) grants to fund the study populations, Hospital of the University of Pennsylvania (HL060290, HL079063), Harborview (GM066946), and Massachusetts General Hospital (HL060710). Additional NIH grants RC2HL101770, HL081619, HL090021, and HL102254 supported the genetic and molecular investigations described herein. NR 78 TC 24 Z9 26 U1 1 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2013 VL 187 IS 9 BP 950 EP 959 DI 10.1164/rccm.201208-1501OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 136SC UT WOS:000318382700014 PM 23449693 ER PT J AU Nowak-Machen, M Schmelzle, M Hanidziar, D Junger, W Exley, M Otterbein, L Wu, Y Csizmadia, E Doherty, G Sitkovsky, M Robson, SC AF Nowak-Machen, Martina Schmelzle, Moritz Hanidziar, Dusan Junger, Wolfgang Exley, Mark Otterbein, Leo Wu, Yan Csizmadia, Eva Doherty, Glen Sitkovsky, Michail Robson, Simon C. TI Pulmonary Natural Killer T Cells Play an Essential Role in Mediating Hyperoxic Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE lung injury; immunology; ATP; P2X7; oxygen ID ISCHEMIA-REPERFUSION INJURY; OXYGEN-TOXICITY; TISSUE-DAMAGE; RECEPTOR; CD39; PROTECTION; MICE; LETHAL; GENERATION; EXPRESSION AB Critically ill patients are routinely exposed to high concentrations of supplemental oxygen for prolonged periods of time, which can be life-saving in the short term, but such exposure also causes severe lung injury and increases mortality. To address this therapeutic dilemma, we studied the mechanisms of the tissue-damaging effects of oxygen in mice. We show that pulmonary invariant natural killer T (iNKT) cells are unexpectedly crucial in the development of acute oxygen-induced lung injury. iNKT cells express high concentrations of the ectonucleotidase CD39, which regulates their state of activation. Both iNKT cell-deficient (J alpha 18(-/-)) and CD39-null mice tolerate hyperoxia, compared with wild-type control mice that exhibit severe lung injury. An adoptive transfer of wild-type iNKT cells into J alpha 18(-/-) mice results in hyperoxic lung injury, whereas the transfer of CD39-null iNKT cells does not. Pulmonary iNKT cell activation and proliferation are modulated by ATP-dependent purinergic signaling responses. Hyperoxic lung injury can be induced by selective P2X7-receptor blockade in CD39-null mice. Our data indicate that iNKT cells are involved in the pathogenesis of hyperoxic lung injury, and that tissue protection can be mediated through ATP-induced P2X7 receptor signaling, resulting in iNKT cell death. In conclusion, our data suggest that iNKT cells and purinergic signaling should be evaluated as potential novel therapeutic targets to prevent hyperoxic lung injury. C1 [Nowak-Machen, Martina] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Nowak-Machen, Martina] Harvard Univ, Sch Med, Boston, MA USA. [Nowak-Machen, Martina; Schmelzle, Moritz; Hanidziar, Dusan; Wu, Yan; Csizmadia, Eva; Robson, Simon C.] Beth Israel Deaconess Med Ctr, Dept Med, Gastroenterol & Transplant Inst, Boston, MA 02215 USA. [Junger, Wolfgang] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Exley, Mark] Harvard Univ, Sch Med, Dept Med, Dana Farber Harvard Canc Ctr, Boston, MA USA. [Doherty, Glen] Univ Coll Dublin, St Vincents Univ Hosp, Dept Med, Dublin 2, Ireland. [Sitkovsky, Michail] Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. RP Robson, SC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Gastroenterol & Transplant Inst, 330 Brookline Ave,E CLS,Room 0612, Boston, MA 02215 USA. EM srobson@bidmc.harvard.edu FU National Institutes of Health [T32 GM007592-32] FX M.N.-M. was supported by National Institutes of Health grant T32 GM007592-32. NR 43 TC 11 Z9 13 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2013 VL 48 IS 5 BP 601 EP 609 DI 10.1165/rcmb.2012-0180OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 137YU UT WOS:000318475300008 PM 23349052 ER PT J AU Hoffmire, CA Piegari, RI Bossarte, RM AF Hoffmire, Claire A. Piegari, Rebecca I. Bossarte, Robert M. TI Misclassification of veteran status on Washington state death certificates for suicides from 1999 to 2008 SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Death certificates; Population surveillance; Public health surveillance; Suicide; Veterans ID REPORTING SYSTEM; MORTALITY; RISK C1 [Hoffmire, Claire A.; Piegari, Rebecca I.; Bossarte, Robert M.] US Dept Vet Affairs, Canandaigua VA Med Ctr, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY 14424 USA. RP Hoffmire, CA (reprint author), US Dept Vet Affairs, Canandaigua VA Med Ctr, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM Claire.Hoffmire@va.gov NR 9 TC 4 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 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2013 VL 23 IS 5 BP 298 EP 300 DI 10.1016/j.annepidem.2013.03.007 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 140OL UT WOS:000318664700012 PM 23621996 ER PT J AU Gray, PJ Efstathiou, JA Shipley, WU AF Gray, Phillip J. Efstathiou, Jason A. Shipley, William U. TI The opportunity cost of androgen suppression in locally advanced prostate cancer SO ASIAN JOURNAL OF ANDROLOGY LA English DT Editorial Material ID PHASE-III TRIAL; QUALITY-OF-LIFE; DEPRIVATION THERAPY; CARDIOVASCULAR MORTALITY; RADIATION-THERAPY; RANDOMIZED-TRIAL; RADIOTHERAPY; DURATION AB The use of androgen suppression therapy (AST) and radiotherapy for locally advanced prostate cancer has become the standard of care worldwide. At the same time, it has become clear that AST carries significant risk for side effects. Recently, Denham and colleagues have reported initial quality of life (QoL) results from the TROG 03.04 RADAR trial. The authors identify clinically meaningful decrements in patient-reported QoL for those treated with 18 months of AST vs. 6 months but only marginal differences at 36 months. Once survival data becomes available, these data will help to frame any benefits seen for longer courses of AST. C1 [Gray, Phillip J.] Harvard Radiat Oncol Program, Boston, MA 02114 USA. [Gray, Phillip J.; Efstathiou, Jason A.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gray, PJ (reprint author), Harvard Radiat Oncol Program, Boston, MA 02114 USA. EM pjgray@partners.org NR 14 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2013 VL 15 IS 3 SI SI BP 356 EP 357 DI 10.1038/aja.2012.166 PG 2 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 140YD UT WOS:000318691500012 PM 23435474 ER PT J AU Luo, NL Chung, BH Wang, XD Klein, RL Tang, CK Garvey, WT Fu, YC AF Luo, Nanlan Chung, B. Hong Wang, Xiangdong Klein, Richard L. Tang, Chao-Ke Garvey, W. Timothy Fu, Yuchang TI Enhanced adiponectin actions by overexpression of adiponectin receptor 1 in macrophages SO ATHEROSCLEROSIS LA English DT Article DE Adiponectin receptor; Macrophage foam cells; Metabolic syndrome ID MONOCYTE-DERIVED MACROPHAGES; PIMA INDIAN POPULATION; INSULIN-RESISTANCE; LIPID-ACCUMULATION; ADIPOSE-TISSUE; CIRCULATING ADIPONECTIN; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; SKELETAL-MUSCLE; PROTEIN ACRP30 AB Objective: Adiponectin is one of several important, metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type II diabetes, and cardiovascular disease. To investigate how enhanced adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice which specifically overexpress the gene coding for adiponectin receptor 1 (AdipoR1) in mouse macrophages using the human scavenger receptor A-I gene (SR-AI) enhancer/promoter. We found that macrophage-specific AdipoR1 transgenic mice (AdR1-TG) presented reduced whole body weight, fat accumulation and liver steatosis when these transgenic mice were fed with a high fat diet. Moreover, these macrophage AdR1-TG mice exhibited enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-alpha, both in the serum and in the insulin target metabolic tissues. Additional studies demonstrated that these macrophage AdR1-TG animals exhibited reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with a low-density lipoprotein receptor (Ldlr) deficient mouse model. Conclusions: These results suggest that AdipoR1 overexpressed in macrophages can physiologically modulate metabolic activities in vivo by enhancing adiponectin actions in distal metabolically active tissues. The AdipoR1 modified macrophages provide unique interactions with the residented tissues/cells, suggesting a novel role of macrophage adiponectin receptor in improving metabolic disorders in vivo. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Luo, Nanlan; Chung, B. Hong; Garvey, W. Timothy; Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Wang, Xiangdong] Shandong Univ, Inst Cell Biol, Jinan 250012, Peoples R China. [Klein, Richard L.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Tang, Chao-Ke] Univ S China, Inst Cardiovasc Res, Hengyang 421001, Peoples R China. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Fu, YC (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Shelby Bldg 1213,1825 Univ Blvd, Birmingham, AL 35294 USA. EM yfu@uab.edu FU American Diabetes Association [1-07-RA-49]; UAB Diabetes Research and Training Center; NIH [DK-083562] FX We thank Dr. Chris Glass (University of California at San Diego) for kindly providing the plasmid vector containing the human scavenger receptor A-I gene (SR-AI) enhancer/promoter. We are grateful to the UAB Diabetes Research and Training Center for providing outstanding core services (NIH P30 DK-56336); especially the helpful technical assistance on en face artery dissections from Ms. Melissa Sammy and Dr. Scott Ballinger in the core facility. This work was supported by grants from American Diabetes Association (1-07-RA-49) and the UAB Diabetes Research and Training Center to YF, and grant from NIH (DK-083562) to TG. NR 51 TC 15 Z9 15 U1 2 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2013 VL 228 IS 1 BP 124 EP 135 DI 10.1016/j.atherosclerosis.2013.02.026 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 139FJ UT WOS:000318567000019 PM 23510830 ER PT J AU Sher, L AF Sher, Leo TI High and low testosterone levels may be associated with suicidal behavior in young and older men, respectively SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY 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 7 Z9 7 U1 0 U2 2 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 MAY PY 2013 VL 47 IS 5 BP 492 EP 493 DI 10.1177/0004867412463976 PG 2 WC Psychiatry SC Psychiatry GA 139GW UT WOS:000318571000021 PM 23047955 ER PT J AU Won, JS Kim, J Paintlia, MK Singh, I Singh, AK AF Won, Je-Seong Kim, Jinsu Paintlia, Manjeet Kaur Singh, Inderjit Singh, Avtar K. TI Role of endogenous psychosine accumulation in oligodendrocyte differentiation and survival: Implication for Krabbe disease SO BRAIN RESEARCH LA English DT Article DE Krabbe disease; Psychosine; Oligodendrocyte; Differentiation; Peroxisome; Myelin ID TANDEM MASS-SPECTROMETRY; TWITCHER MOUSE; GALACTOSYLSPHINGOSINE PSYCHOSINE; PROGENITOR CELLS; GLIAL-CELLS; FATTY-ACIDS; PEROXISOMES; BRAIN; BIOSYNTHESIS; ACTIVATION AB Krabbe disease is a lethal, demyelinating condition caused by genetic deficiency of galactocerebrosidase (GALC) and resultant accumulation of its cytotoxic substrate, psychosine (galactosylsphingosine), primarily in oligodendrocytes (OLs). Psychosine is generated by galactosylation of sphingosine by UDP-galactose:ceramide galactosyltransferase (CGT), a galactosylceramide synthesizing enzyme which is primarily expressed in OLs. The expression of CGT and the synthesis of galactosyl-sphingolipids are associated with the terminal differentiation of OL, but little is known about the participation of endogenous psychosine accumulation in OL differentiation under GALC deficient conditions. In this study, we report that accumulation of endogenous psychosine under GALC deficient Krabbe conditions impedes OL differentiation process both by decreasing the expression of myelin lipids and protein and by inducing the cell death. of maturating OLs. The psychosine pathology under GALC deficient conditions involves participation of secretory phospholipase A(2) (sPLA(2)) activation and increase in its metabolites, as evidenced by attenuation of psychosine-induced pathology by treatment with pharmacological inhibitor of sPLA(2) 7,7-dimethyleicosadienoic acid (DEDA). These observations suggest for potential therapeutic efficacy of sPLA(2) inhibitor in Krabbe disease. Published by Elsevier B.V. C1 [Won, Je-Seong; Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Kim, Jinsu; Paintlia, Manjeet Kaur; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Pathol & Lab Med Serv, Charleston, SC USA. RP Singh, AK (reprint author), Ralph H Johnson Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC USA. EM Avtar.Singh@va.gov FU National Institutes of Health (NIH) [NS064195]; NIH; Veterans Administration (VA) [NS022576, NS037766, BX001072] FX This work was supported by a National Institutes of Health (NIH) Grant (NS064195) and supported, in part, by grants from NIH and Veterans Administration (VA) Grant (NS022576, NS037766, and BX001072). We also acknowledge Ms. Joyce Bryan and Ms. Chara Williams for their help in procurement of animals and supplies. NR 31 TC 16 Z9 16 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 2013 VL 1508 BP 44 EP 52 DI 10.1016/j.brainres.2013.02.024 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 141UE UT WOS:000318751200005 PM 23438514 ER PT J AU Modi, S Saura, C Henderson, C Lin, NU Mahtani, R Goddard, J Rodenas, E Hudis, C O'Shaughnessy, J Baselga, J AF Modi, Shanu Saura, Cristina Henderson, Charles Lin, Nancy U. Mahtani, Reshma Goddard, Jill Rodenas, Eduardo Hudis, Clifford O'Shaughnessy, Joyce Baselga, Jose TI A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Phase 2; Retaspimycin plus trastuzumab; HER2+MBC ID PROTEIN 90 INHIBITOR; TANESPIMYCIN 17-AAG; PHASE-II; PHARMACOKINETICS; COMBINATION; EFFICACY; SAFETY; KINASE; CELLS; ERBB3 AB Heat shock protein 90 (Hsp90) facilitates maturation and stability of HER2. Combining an Hsp90 inhibitor and trastuzumab has demonstrated anti-tumor effects in patients with HER2+ breast cancer. Adults with measurable, locally advanced or metastatic HER2+ breast cancer and prior trastuzumab treatment were enrolled in a phase 2 trial employing weekly 300 mg/m(2) retaspimycin HCl, a potent Hsp90 inhibitor, with 6 mg/kg trastuzumab every 3 weeks. A Simon's two-stage design determined trial expansion by dose-limiting toxicity (DLT) and response rates. Pharmacokinetics and electrocardiograms were evaluated. Twenty-six patients with median age 52.5 years (range 33-72) enrolled with a median of six prior chemotherapeutic regimens (range 2-20). On study, patients received a median of three treatment cycles (range 1-12). No DLTs were observed. Most adverse events (AEs) were grade 1 or 2; common treatment-related AEs included fatigue (46 %), nausea (31 %), and diarrhea (23 %). One patient had treatment-related serious AEs of grade 1 diarrhea and grade 3 hypokalemia. grade 3 transaminase elevation occurred in one patient (4 %) who also had metastatic liver disease. Sixteen patients (62 %) had stable disease, with a median on-study duration of 2.4 months (range 1.1-8.2). No confirmed responses were observed. Retaspimycin HCl at 300 mg/mA(2) weekly in combination with trastuzumab was well tolerated and without significant toxicities. Modest clinical activity was observed, but did not meet criteria for trial expansion. The safety profile for patients on study raises the possibility of retaspimycin HCl underdosing that limited efficacy. Studies employing higher doses are ongoing. C1 [Modi, Shanu; Hudis, Clifford; Baselga, Jose] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, New York, NY 10065 USA. [Saura, Cristina] Vall dHebron Univ Hosp, VHIO, Barcelona, Spain. [Henderson, Charles] Peachtree Hematol Oncol Consultants PC, Atlanta, GA USA. [Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mahtani, Reshma] Univ Miami, Sylvester Comprehens Canc Ctr, Deerfield Beach, FL USA. [Goddard, Jill; Rodenas, Eduardo] Infin Pharmaceut Inc, Cambridge, MA USA. [O'Shaughnessy, Joyce] US Oncol, Texas Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. RP Modi, S (reprint author), Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, 300 East 66th St, New York, NY 10065 USA. EM modis@mskcc.org OI Modi, Shanu/0000-0001-6427-7373; Saura, Cristina/0000-0001-8296-5065 FU Infinity Pharmaceuticals, Inc., Cambridge, MA, USA FX Support for this trial was provided by Infinity Pharmaceuticals, Inc., Cambridge, MA, USA. NR 14 TC 25 Z9 25 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 MAY PY 2013 VL 139 IS 1 BP 107 EP 113 DI 10.1007/s10549-013-2510-5 PG 7 WC Oncology SC Oncology GA 138QX UT WOS:000318524600011 PM 23580070 ER PT J AU Rath, MG Masciari, S Gelman, R Miron, A Miron, P Foley, K Richardson, AL Krop, IE Verselis, SJ Dillon, DA Garber, JE AF Rath, Michelle G. Masciari, Serena Gelman, Rebecca Miron, Alexander Miron, Penelope Foley, Kathleen Richardson, Andrea L. Krop, Ian E. Verselis, Sigitas J. Dillon, Deborah A. Garber, Judy E. TI Prevalence of germline TP53 mutations in HER2+breast cancer patients SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Li-Fraumeni syndrome; Breast cancer; TP53 ID LI-FRAUMENI-SYNDROME; SENSITIVE GEL-ELECTROPHORESIS; ONSET BREAST-CANCER; P53 MUTATIONS; FAMILIES; TUMORS; CRITERIA AB Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2+ (63-83 %). We assessed the prevalence of germline TP53 mutations in a cohort of women with HER2+ breast cancer diagnosed age a parts per thousand currency sign50 years. We identified blood specimens from 213 women with primary invasive HER2+ breast cancer age a parts per thousand currency sign50 years from a single center. Exon grouping analysis sequencing and multiplex ligation-dependent probe amplification techniques were used to screen for germline TP53 mutations. Among 213 women with HER2+ breast cancer age a parts per thousand currency sign50 years, 3 (ages at diagnosis 23, 32, 44 years) were found to carry a TP53 mutation (1.4 %, 95 % CI 0.3-4.1 %). ER/PR status was not uniform. Two TP53 carriers met Chompret criteria for LFS; none met classic LFS criteria. Although two-thirds of breast cancers in women with TP53 mutations are HER2+, we observed a low prevalence of germline TP53 mutations among unselected young women with HER2+ breast cancer. Given the potential clinical impact, consideration of germline TP53 testing should be given to young women with HER2+ breast cancer, especially if family cancer history is notable. C1 [Rath, Michelle G.; Masciari, Serena; Krop, Ian E.; Garber, Judy E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Miron, Alexander; Miron, Penelope; Foley, Kathleen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Richardson, Andrea L.; Dillon, Deborah A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Verselis, Sigitas J.] Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02215 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Judy_Garber@dfci.harvard.edu FU Breast Cancer Research Foundation; Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer Grant [P50 CA89393]; German Research Foundation FX Dr. Elgene Lim for helpful comments on the manuscript. The work was supported by the Breast Cancer Research Foundation and the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer Grant (No. P50 CA89393). Michelle Rath received funding from the German Research Foundation. NR 28 TC 6 Z9 6 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2013 VL 139 IS 1 BP 193 EP 198 DI 10.1007/s10549-012-2375-z PG 6 WC Oncology SC Oncology GA 138QX UT WOS:000318524600020 PM 23580068 ER PT J AU Herrin, MA Feemster, LC Crothers, K Uman, JE Bryson, CL Au, DH AF Herrin, Melissa A. Feemster, Laura Cecere Crothers, Kristina Uman, Jane E. Bryson, Chris L. Au, David H. TI Combination Antihypertensive Therapy Among Patients With COPD SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CONGESTIVE-HEART-FAILURE; LIPID-LOWERING TREATMENT; CALCIUM-CHANNEL BLOCKER; ATTACK TRIAL ALLHAT; RANDOMIZED-TRIAL; BLOOD-PRESSURE; CARDIOVASCULAR MORBIDITY; PHARMACY RECORDS; BETA-BLOCKERS AB Background: COPD and hypertension both increase the risk of congestive heart failure (CHF). Current clinical trials do not inform the selection of combination antihypertensive therapy among patients with COPD. We performed a comparative effectiveness study to investigate whether choice of dual agent antihypertensive therapy is associated with risk of hospitalization for CHF among patients with these two conditions. Methods: We identified a cohort of 7,104 patients with COPD and hypertension receiving care within Veterans Administration hospitals between January 2001 and December 2006, with follow-up through April 2009. We included only patients prescribed two antitypertensive medications. We used Cox proportional hazard models for statistical analysis. Results: Compared with beta-blockers plus an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, patients prescribed a thiazide diuretic plus a beta-blocker (adjusted hazard ratio [HR], 0.49; 95% CI, 0.32-0.75), a thiazide plus an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (adjusted HR, 0.50; 95% CI, 0.35-0.71), and a thiazide plus a calcium channel blocker (adjusted HR, 0.55; 95% CI, 0.35-0.88) had a significantly lower risk of hospitalization for CHF. After stratification by history of CHF, we found that this association was isolated to patients without a history of CHF. Adjustment for patient characteristics and comorbidities had a small effect on risk of hospitalization. Choice of antihypertensive medication combination had no significant association with risk of COPD exacerbation. Conclusions: Among patients with comorbid hypertension and COPD requiring two antitypertensive agents, combination therapy that includes a thiazide diuretic was associated with a significantly lower risk of hospitalization for CHF among patients without a history of CHF. C1 [Herrin, Melissa A.; Feemster, Laura Cecere; Uman, Jane E.; Bryson, Chris L.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Feemster, Laura Cecere; Crothers, Kristina; Au, David H.] Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Bryson, Chris L.] Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. RP Herrin, MA (reprint author), 1100 Olive Way,Ste 1400, Seattle, WA 98101 USA. EM herrinmelissa@gmail.com OI Crothers, Kristina/0000-0001-9702-0371 FU Department of Veterans Affairs, Health Services Research and Development; American Lung Association [CI-51755N]; Veterans Affairs Health Services Research and Development fellowship [TPM 61-037]; Gilead FX This material is based on work supported by the Department of Veterans Affairs, Health Services Research and Development, and American Lung Association Grant CI-51755N. Dr Feemster is supported by a Veterans Affairs Health Services Research and Development fellowship (TPM 61-037).; The authors have reported to CHEST the following conflicts of interest: Drs Bryson and Au are coinvestigators on a grant from Gilead for work unrelated to this manuscript. Dr Au is a research consultant for Robert Bosch LLC. Mss Herrin and Uman and Drs Feemster and Crothers have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 33 TC 4 Z9 4 U1 2 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2013 VL 143 IS 5 BP 1312 EP 1320 DI 10.1378/chest.12-1770 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 137TS UT WOS:000318461700022 PM 23287970 ER PT J AU Bernstein, AS Rice, MB AF Bernstein, Aaron S. Rice, Mary B. TI Lungs in a Warming World Climate Change and Respiratory Health SO CHEST LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; FIRE SMOKE EXPOSURE; AIR-POLLUTION; AMBIENT OZONE; SOUTHERN CALIFORNIA; HOSPITAL ADMISSIONS; ASTHMA; POLLEN; ASSOCIATIONS; TEMPERATURE AB Climate change is a health threat no less consequential than cigarette smoking. Increased concentrations of greenhouse gases, and especially CO2, in the earth's atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, temperature variability, air pollution, forest fires, droughts, and floods, all of which put respiratory health at risk. These changes in climate and air quality substantially increase respiratory morbidity and mortality for patients with common chronic lung diseases such as asthma and COPD and other serious lung diseases. Physicians have a vital role in addressing climate change, just as they did with tobacco, by communicating how climate change is a serious, but remediable, hazard to their patients. C1 [Bernstein, Aaron S.] Harvard Univ, Sch Publ Hlth, Boston Childrens Hosp, Ctr Hlth & Global Environm, Boston, MA 02115 USA. [Bernstein, Aaron S.] Boston Childrens Hosp, Div Gen Med, Boston, MA 02215 USA. [Rice, Mary B.] Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. RP Bernstein, AS (reprint author), Boston Childrens Hosp, Div Gen Pediat, 300 Longwood Ave,Hunnewell 2, Boston, MA 02215 USA. EM aaron.bernstein@childrens.harvard.edu OI Rice, Mary/0000-0003-2538-391X NR 50 TC 14 Z9 14 U1 2 U2 38 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2013 VL 143 IS 5 BP 1455 EP 1459 DI 10.1378/chest.12-2384 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 137TS UT WOS:000318461700039 PM 23648909 ER PT J AU Goyal, L Muzumdar, MD Zhu, AX AF Goyal, Lipika Muzumdar, Mandar D. Zhu, Andrew X. TI Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; FACTOR MESSENGER-RNA; C-MET; TRANSGENIC MICE; SCATTER FACTOR; IN-VIVO; LIVER-REGENERATION; MOLECULAR-CLONING; CELL-LINES AB Hepatocellular carcinoma (HCC) is a significant cause of cancer-related morbidity and mortality worldwide. Despite improvements in local therapies, including surgical resection, liver transplantation, and transarterial embolization, the prognosis remains poor for the majority of patients who develop recurrence or present with advanced disease. Systemic therapy with the tyrosine kinase inhibitor sorafenib represents a milestone in advanced HCC but provides a limited survival benefit. Ongoing efforts to study hepatocarcinogenesis have identified an important role for c-MET signaling in the promotion of tumor growth, angiogenesis, and metastasis. In this review, we summarize the preclinical data from human tissue, cell lines, and animal models that implicate c-MET in the pathogenesis of HCC. We also evaluate potential biomarkers that may estimate prognosis or predict response to c-MET inhibitors for more rational clinical trial design. Finally, we discuss the latest clinical trials of c-MET inhibitors in advanced HCC. (c) 2013 AACR. C1 [Goyal, Lipika; Muzumdar, Mandar D.; Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Goyal, Lipika; Muzumdar, Mandar D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH-PB 232, Boston, MA 02114 USA. EM azhu@partners.org FU NCI NIH HHS [L30 CA171131] NR 71 TC 80 Z9 86 U1 3 U2 31 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 MAY 1 PY 2013 VL 19 IS 9 BP 2310 EP 2318 DI 10.1158/1078-0432.CCR-12-2791 PG 9 WC Oncology SC Oncology GA 136KX UT WOS:000318361900007 PM 23388504 ER PT J AU De Rienzo, A Richards, WG Yeap, BY Coleman, MH Sugarbaker, PE Chirieac, LR Wang, YYE Quackenbush, J Jensen, RV Bueno, R AF De Rienzo, Assunta Richards, William G. Yeap, Beow Y. Coleman, Melissa H. Sugarbaker, Peter E. Chirieac, Lucian R. Wang, Yaoyu E. Quackenbush, John Jensen, Roderick V. Bueno, Raphael TI Sequential Binary Gene Ratio Tests Define a Novel Molecular Diagnostic Strategy for Malignant Pleural Mesothelioma SO CLINICAL CANCER RESEARCH LA English DT Article ID EXPRESSION PROFILING DATA; LUNG-CANCER; MICROARRAY; SURVIVAL; BIOLOGY AB Purpose: To develop a standardized approach for molecular diagnostics, we used the gene expression ratio bioinformatic technique to design a molecular signature to diagnose malignant pleural mesothelioma (MPM) from among other potentially confounding diagnoses and differentiate the epithelioid from the sarcomatoid histologic subtype of MPM. In addition, we searched for pathways relevant in MPM in comparison with other related cancers to identify unique molecular features in MPM. Experimental Design: We conducted microarray analysis on 113 specimens including MPMs and a spectrum of tumors and benign tissues comprising the differential diagnosis of MPM. We generated a sequential combination of binary gene expression ratio tests able to discriminate MPM from other thoracic malignancies. We compared this method with other bioinformatic tools and validated this signature in an independent set of 170 samples. Functional enrichment analysis was conducted to identify differentially expressed probes. Results: A sequential combination of gene expression ratio tests was the best molecular approach to distinguish MPM from all the other samples. Bioinformatic and molecular validations showed that the sequential gene ratio tests were able to identify the MPM samples with high sensitivity and specificity. In addition, the gene ratio technique was able to differentiate the epithelioid from the sarcomatoid type of MPM. Novel genes and pathways specifically activated in MPM were identified. Conclusions: New clinically relevant molecular tests have been generated using a small number of genes to accurately distinguish MPMs from other thoracic samples, supporting our hypothesis that the gene expression ratio approach could be a useful tool in the differential diagnosis of cancers. Clin Cancer Res; 19(9); 2493-502. (C) 2013 AACR. C1 [De Rienzo, Assunta; Richards, William G.; Coleman, Melissa H.; Sugarbaker, Peter E.; Bueno, Raphael] Brigham & Womens Hosp, Thorac Surg Oncol Lab, Boston, MA 02115 USA. [De Rienzo, Assunta; Richards, William G.; Coleman, Melissa H.; Sugarbaker, Peter E.; Bueno, Raphael] Brigham & Womens Hosp, Int Mesothelioma Program, Div Thorac Surg, Boston, MA 02115 USA. [De Rienzo, Assunta; Richards, William G.; Yeap, Beow Y.; Coleman, Melissa H.; Sugarbaker, Peter E.; Chirieac, Lucian R.; Bueno, Raphael] Harvard Univ, Sch Med, Boston, MA USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wang, Yaoyu E.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Jensen, Roderick V.] Virginia Tech, Dept Biol Sci, Blacksburg, VA USA. RP Bueno, R (reprint author), Brigham & Womens Hosp, Thorac Surg Oncol Lab, 75 Francis St, Boston, MA 02115 USA. EM rbueno@partners.org FU National Cancer Institute [RO1-120528]; International Mesothelioma Program at BWH; Vancouver Foundation FX This work was supported by National Cancer Institute (RO1-120528 to R. Bueno) as well as by grants from the International Mesothelioma Program at BWH (to R. Bueno) and the Maurice Favell Fund at the Vancouver Foundation (to R. Bueno). NR 34 TC 3 Z9 3 U1 0 U2 2 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 MAY 1 PY 2013 VL 19 IS 9 BP 2493 EP 2502 DI 10.1158/1078-0432.CCR-12-2117 PG 10 WC Oncology SC Oncology GA 136KX UT WOS:000318361900023 PM 23493352 ER PT J AU Roh, JL Wang, XV Manola, J Sidransky, D Forastiere, AA Koch, WM AF Roh, Jong-Lyel Wang, Xin Victoria Manola, Judith Sidransky, David Forastiere, Arlene A. Koch, Wayne M. TI Clinical Correlates of Promoter Hypermethylation of Four Target Genes in Head and Neck Cancer: A Cooperative Group Correlative Study SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; I LUNG-CANCER; DNA METHYLATION; HUMAN-PAPILLOMAVIRUS; SALIVARY RINSES; SURVIVAL; P16; MUTATIONS; MARKER; INACTIVATION AB Purpose: Promoter hypermethylation is a well-documented mechanism for tumor-specific alteration of suppressor gene activity in human malignancy including head and neck cancer (HNC). The abrogation of specific suppressor gene activity may influence tumor behavior and clinical outcome. In this study we examined methylation of DCC, KIF1A, EDNRB, and p16(INK4a) in a large cohort of HNC patients from Eastern Cooperative Group (ECOG) 4393/Radiation Therapy Oncology Group (RTOG) 9614 to identify clinical correlates of methylation of these genes. Experimental Design: Methylation was assessed by quantitative methylation-specific PCR in DNA from tumor specimens and was considered as a continuous and a binary variable. Clinical data including demographics, stage, risk factor exposure, treatment, and outcome were collected by ECOG and RTOG. Methylation status was also correlated with mutation of TP53 (previously reported) and human papilloma virus status. Results: Methylation results were available for 368 cases, 353 of which also have p53 mutation status. At least one methylation event was present in all tumors. In multivariate analysis of the entire cohort, methylation of p16 was associated with decreased survival (HR = 1.008; P = 0.045). However, in tumors with disruptive TP53 mutation (poor prognostic group), the additional presence of methylation of p16 was protective (P = 0.019 considering p16 methylation as a continuous variable). Conclusion: Methylation of tumor-related genes contributes to the biological behavior of HNC and influences overall survival in conjunction with other known prognostic molecular events. Clin Cancer Res; 19(9); 2528-40. (C) 2013 AACR. C1 [Roh, Jong-Lyel; Sidransky, David; Koch, Wayne M.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Sch Med, Baltimore, MD 21287 USA. [Forastiere, Arlene A.] Johns Hopkins Univ, Dept Oncol, Sch Med, Baltimore, MD 21287 USA. [Roh, Jong-Lyel] Univ Ulsan, Coll Med, Dept Otolaryngol, Asan Med Ctr, Seoul, South Korea. [Wang, Xin Victoria; Manola, Judith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Xin Victoria] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Koch, WM (reprint author), Johns Hopkins Univ, Dept Otolaryngol, Sch Med, 601 North Caroline St,JHOC 6221, Baltimore, MD 21287 USA. EM wkoch@jhmi.edu FU National Institute of Health; National Institute of Dental and Craniofacial Research [R01 DE013152-11] FX This work is supported by grants from National Institute of Health and the National Institute of Dental and Craniofacial Research (R01 DE013152-11). NR 39 TC 16 Z9 16 U1 0 U2 4 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 MAY 1 PY 2013 VL 19 IS 9 BP 2528 EP 2540 DI 10.1158/1078-0432.CCR-12-3047 PG 13 WC Oncology SC Oncology GA 136KX UT WOS:000318361900026 PM 23444219 ER PT J AU Ohashi, K Sequist, LV Arcila, ME Lovly, CM Chen, X Rudin, CM Moran, T Camidge, DR Vnencak-Jones, CL Berry, L Pan, YM Sasaki, H Engelman, JA Garon, EB Dubinett, SM Franklin, WA Riely, GJ Sos, ML Kris, MG Dias-Santagata, D Ladanyi, M Bunn, PA Pao, W AF Ohashi, Kadoaki Sequist, Lecia V. Arcila, Maria E. Lovly, Christine M. Chen, Xi Rudin, Charles M. Moran, Teresa Camidge, David Ross Vnencak-Jones, Cindy L. Berry, Lynne Pan, Yumei Sasaki, Hidefumi Engelman, Jeffrey A. Garon, Edward B. Dubinett, Steven M. Franklin, Wilbur A. Riely, Gregory J. Sos, Martin L. Kris, Mark G. Dias-Santagata, Dora Ladanyi, Marc Bunn, Paul A., Jr. Pao, William TI Characteristics of Lung Cancers Harboring NRAS Mutations SO CLINICAL CANCER RESEARCH LA English DT Article ID COPY NUMBER GAINS; WILD-TYPE RAS; N-RAS; K-RAS; CLINICAL-FEATURES; SOMATIC MUTATIONS; BRAF MUTATIONS; TOBACCO-SMOKE; NEVER SMOKERS; CELL AB Purpose: We sought to determine the frequency and clinical characteristics of patients with lung cancer harboring NRAS mutations. We used preclinical models to identify targeted therapies likely to be of benefit against NRAS-mutant lung cancer cells. Experimental Design: We reviewed clinical data from patients whose lung cancers were identified at six institutions or reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) to harbor NRAS mutations. Six NRAS-mutant cell lines were screened for sensitivity against inhibitors of multiple kinases (i.e., EGFR, ALK, MET, IGF-1R, BRAF, PI3K, and MEK). Results: Among 4,562 patients with lung cancers tested, NRAS mutations were present in 30 (0.7%; 95% confidence interval, 0.45%-0.94%); 28 of these had no other driver mutations. 83% had adenocarcinoma histology with no significant differences in gender. While 95% of patients were former or current smokers, smoking-related G:C>T:A transversions were significantly less frequent in NRAS-mutated lung tumors than KRAS-mutant non-small cell lung cancer [NSCLC; NRAS: 13% (4/30), KRAS: 66% (1772/2733), P < 0.00000001]. Five of 6 NRAS-mutant cell lines were sensitive to the MEK inhibitors, selumetinib and trametinib, but not to other inhibitors tested. Conclusion: NRAS mutations define a distinct subset of lung cancers (similar to 1%) with potential sensitivity to MEK inhibitors. Although NRAS mutations are more common in current/former smokers, the types of mutations are not those classically associated with smoking. Clin Cancer Res; 19(9); 2584-91. (C) 2013 AACR. C1 [Ohashi, Kadoaki; Lovly, Christine M.; Pan, Yumei; Pao, William] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Ohashi, Kadoaki; Lovly, Christine M.; Pan, Yumei; Pao, William] Vanderbilt Univ, Sch Med, Dept Med, Div Hematol Oncol, Nashville, TN 37212 USA. [Chen, Xi] Vanderbilt Univ, Sch Med, Dept Biostat, Div Canc Biostat, Nashville, TN 37212 USA. [Berry, Lynne] Vanderbilt Univ, Sch Med, Ctr Quantitat Sci, Nashville, TN 37212 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Microbiol, Nashville, TN USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Immunol, Nashville, TN USA. [Dias-Santagata, Dora] Dept Pathol, Boston, MA USA. [Sequist, Lecia V.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Sequist, Lecia V.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Arcila, Maria E.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Riely, Gregory J.; Kris, Mark G.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, Thorac Oncol Serv, New York, NY 10021 USA. [Rudin, Charles M.] Johns Hopkins Univ, Baltimore, MD USA. [Moran, Teresa] Univ Autonoma Barcelona, Catalan Inst Oncol, E-08193 Barcelona, Spain. [Moran, Teresa] Hosp Badalona Germans Trias & Pujol, Barcelona, Spain. [Camidge, David Ross; Franklin, Wilbur A.; Bunn, Paul A., Jr.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Sasaki, Hidefumi] Nagoya City Univ, Sch Med, Dept Surg 2, Nagoya, Aichi 467, Japan. [Garon, Edward B.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Translat Oncol Res Lab, Div Hematol Oncol, Santa Monica, CA USA. [Sos, Martin L.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA USA. [Sos, Martin L.] Max Planck Gesell, Klaus Joachim Zulch Labs, Max Planck Inst Neurol Res, Cologne, Germany. [Sos, Martin L.] Fac Med, Cologne, Germany. [Sos, Martin L.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. [Sos, Martin L.] Univ Cologne, Ctr Integrated Oncol Koln Bonn, D-50931 Cologne, Germany. RP Pao, W (reprint author), Vanderbilt Ingram Canc Ctr, 2220 Pierce Ave 777 PRB, Nashville, TN 37232 USA. EM william.pao@vanderbilt.edu OI Kris, Mark/0000-0002-7317-5341 FU NIH NCI [RC2-CA148394, R01-CA121210, P01-CA129243, U54-CA143798]; Program of Research Excellence in Lung Cancer grant [CA90949]; VICC Cancer Center Core [P30-CA68485] FX This work was supported by NIH NCI grants RC2-CA148394, R01-CA121210, P01-CA129243, and U54-CA143798. W. Pao received additional support from Vanderbilt's Specialized Program of Research Excellence in Lung Cancer grant (CA90949) and the VICC Cancer Center Core grant (P30-CA68485). NR 47 TC 36 Z9 38 U1 1 U2 7 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 MAY 1 PY 2013 VL 19 IS 9 BP 2584 EP 2591 DI 10.1158/1078-0432.CCR-12-3173 PG 8 WC Oncology SC Oncology GA 136KX UT WOS:000318361900031 PM 23515407 ER PT J AU Rao, MK Morris, CD O'Malley, JP Davis, MM Mori, M Anderson, S AF Rao, Maya K. Morris, Cynthia D. O'Malley, Jean P. Davis, Melinda M. Mori, Motomi Anderson, Sharon TI Documentation and Management of CKD in Rural Primary Care SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; UNITED-STATES; BLOOD-PRESSURE; RENAL-DISEASE; NEPHROLOGY CARE; ESTIMATED GFR; HEALTH; MORTALITY; ACCESS AB Background and objectives Recognition of CKD by primary care practitioners is essential in rural communities where nephrology access is limited. This study determined the prevalence of undocumented CKD in patients cared for in rural primary care practices and evaluated characteristics associated with undocumented CKD as well as CKD management. Design, setting, participants, & measurements A retrospective cohort study, conducted within the Oregon Rural Practice Based Research Network, consisted of 865 CKD patients with serum creatinine >= 1.5 mg/dl in males and >= 1.3 mg/dl in females and an estimated GFR<60 ml/min per 1.73 m(2). Documentation of a CKD diagnosis and laboratory values were abstracted by chart review. Results Of CKD patients, 51.9% had no documentation of CKD. Undocumented CKD occurred more frequently in female patients (adjusted odds ratio=2.93, 95% confidence interval=2.04, 4.21). The association of serum creatinine reporting versus automating reporting of estimated GFR on CKD documentation was dependent on patient sex, years of practitioner experience, and practitioner clinical training. Hypertensive patients with documented CKD were more likely to have a BP medication change than patients with undocumented CKD (odds ratio=2.07, 95% confidence interval=1.15, 3.73). Only 2 of 449 patients with undocumented CKD were comanaged with a nephrologist compared with 20% of patients with documented CKD (odds ratio=53.20, 95% confidence interval=14.90, 189.90). Conclusions Undocumented CKD in a rural primary care setting is frequent, particularly in female patients. Depending on practitioner characteristics, automatic reporting of estimated GFR might improve documentation of CKD in this population. C1 [Rao, Maya K.; Anderson, Sharon] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA. [Morris, Cynthia D.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [O'Malley, Jean P.; Mori, Motomi] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA. [Davis, Melinda M.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Davis, Melinda M.] Oregon Hlth & Sci Univ, Oregon Rural Practice Based Res Network, Portland, OR 97201 USA. [Anderson, Sharon] Portland VA Med Ctr, Dept Med, Portland, OR USA. RP Rao, MK (reprint author), Columbia Univ, Med Ctr, Div Nephrol, 622 West 168th St,PH 4, New York, NY 10032 USA. EM mr2971@columbia.edu FU Medical Research Foundation of Oregon Early Clinical Investigator Grant; National Kidney Foundation; Oregon Clinical and Translational Research Institute Grant [1 UL 1 RRO2414001]; National Institutes of Health [T32 DK 067864] FX This research was supported by a Medical Research Foundation of Oregon Early Clinical Investigator Grant (to M.K.R), a National Kidney Foundation Research Fellowship (to M.K.R), Oregon Clinical and Translational Research Institute Grant 1 UL 1 RRO2414001 (to C.D.M.), and National Institutes of Health Grant T32 DK 067864 (to S.A.). NR 36 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2013 VL 8 IS 5 BP 739 EP 748 DI 10.2215/CJN.02410312 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 138TB UT WOS:000318531800008 PM 23371962 ER PT J AU Orenes-Pinero, E Manzano-Fernandez, S Lopez-Cuenca, A Marin, F Valdes, M Januzzi, JL AF Orenes-Pinero, Esteban Manzano-Fernandez, Sergio Lopez-Cuenca, Angel Marin, Francisco Valdes, Mariano Januzzi, James L. TI beta-Trace Protein: From GFR Marker to Cardiovascular Risk Predictor SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID PROSTAGLANDIN-D-SYNTHASE; GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; FLUID SHEAR-STRESS; VASCULAR ENDOTHELIAL-CELLS; CYSTATIN-C; SERUM CREATININE; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); CORONARY ANGIOPLASTY; URINARY EXCRETIONS AB beta-trace protein, also known as Lipocalin type prostaglandin D synthase, is a low-molecular mass glycoprotein (between 23,000 and 29,000 Da depending on the degree of glycosylation) that converts prostaglandin H2 into prostaglandin D2. beta-trace protein was initially isolated from cerebrospinal fluid and served as a marker of cerebrospinal fluid leakage; however, its cDNA and gene have been isolated in numerous human body tissues, including central nervous system, retina, melanocytes, heart, and male genital organs. In recent years, beta-trace protein has emerged as a promising novel endogenous marker of GFR, representing a more sensitive marker for mild kidney dysfunction than serum creatinine. In this regard, beta-trace protein has been proposed as an alternative marker to Cystatin C for measuring kidney function. Beyond its role for estimating renal function, beta-trace protein is also emerging as a novel biomarker in cardiovascular risk. It has been associated with several cardiovascular disorders, playing a potential role for prognostic stratification in patients with acutely decompensated heart failure and acute coronary syndromes and being advocated as a novel marker for cardiovascular risk prediction. Clin J Am Soc Nephrol 8: 873-881, 2013. doi: 10.2215/CJN.08870812 C1 [Orenes-Pinero, Esteban; Manzano-Fernandez, Sergio; Lopez-Cuenca, Angel; Marin, Francisco; Valdes, Mariano] Univ Murcia, Dept Cardiol, Hosp Univ Virgen Arrixaca, Murcia, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia, Murcia, Spain; DeSanctis Clinical Scholar Endowment FX E.O.-P. is supported by a postdoctoral contract from Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia, Murcia, Spain. J.L.J. is supported by the DeSanctis Clinical Scholar Endowment. NR 54 TC 17 Z9 19 U1 0 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2013 VL 8 IS 5 BP 873 EP 881 DI 10.2215/CJN.08870812 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 138TB UT WOS:000318531800025 PM 23335042 ER PT J AU Alexander, BM Ligon, KL Wen, PY AF Alexander, Brian M. Ligon, Keith L. Wen, Patrick Y. TI Enhancing radiation therapy for patients with glioblastoma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE glioblastoma; radiation therapy; radiosensitizer ID HUMAN-MALIGNANT GLIOMA; DNA-DAMAGE RESPONSE; HISTONE DEACETYLASE INHIBITOR; TUMOR-CELL RADIOSENSITIVITY; STRAND BREAK REPAIR; HIGH-GRADE GLIOMAS; HOMOLOGOUS RECOMBINATION REPAIR; IN-VIVO RADIOSENSITIZATION; TRANS-SODIUM CROCETINATE; STEM-LIKE CELLS AB Radiation therapy has been the foundation of therapy following maximal surgical resection in patients with newly diagnosed glioblastoma for decades and the primary therapy for unresected tumors. Using the standard approach with radiation and temozolomide, however, outcomes are poor, and glioblastoma remains an incurable disease with the majority of recurrences and progression within the radiation treatment field. As such, there is much interest in elucidating the mechanisms of resistance to radiation therapy and in developing novel approaches to overcoming this treatment resistance. C1 [Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Brigham & Womens Canc Ctr, Dept Pathol, Boston, MA 02215 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. RP Alexander, BM (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM bmalexander@lroc.harvard.edu FU Plexxikon; GlaxoSmithKline; Vertex; Amgen; AstraZeneca; Boehringer Ingelheim; Esai; Exelixis; Genentech/Roche; Geron; Medimmune; Merck; Novartis; sanofi-aventis; Vascular Biogenics FX Research support was provided by Plexxikon, GlaxoSmithKline and Vertex to KL Ligon. Amgen, AstraZeneca, Boehringer Ingelheim, Esai, Exelixis, Genentech/Roche, Geron, Medimmune, Merck, Novartis, sanofi-aventis and Vascular Biogenics provided research support to PY Wen. PY Wen is on the advisory board for Novartis, Genentech/Roche and is a speaker for Merck, Genentech/Roche and GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 148 TC 7 Z9 7 U1 2 U2 16 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAY PY 2013 VL 13 IS 5 BP 569 EP 581 DI 10.1586/ERA.13.44 PG 13 WC Oncology SC Oncology GA 138XM UT WOS:000318545000013 PM 23617348 ER PT J AU Pau, C Saxena, R Welt, CK AF Pau, Cindy Saxena, Richa Welt, Corrine Kolka TI Evaluating reported candidate gene associations with polycystic ovary syndrome SO FERTILITY AND STERILITY LA English DT Article DE Candidate genes; genome-wide association ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; AFFECTED WOMEN; ADMIXTURE MAP; VARIANTS; PREVALENCE; 5-ALPHA-REDUCTASE; POLYMORPHISMS; ADIPONECTIN AB Objective: To replicate variants in candidate genes associated with polycystic ovary syndrome (PCOS) in a population of European women with PCOS and control subjects. Design: Case-control association analysis and meta-analysis. Setting: Major academic hospital. Patient(s): Women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years. Intervention(s): Variants previously associated with PCOS in candidate gene studies were genotyped (n = 39). Metabolic, reproductive, and anthropomorphic parameters were examined as a function of the candidate variants. All genetic association analyses were adjusted for age, body mass index, and ancestry and were reported after correction for multiple testing. Main Outcome Measure(s): Association of candidate gene variants with PCOS. Result(s): Three variants, rs3797179 (SRD5A1), rs12473543 (POMC), and rs1501299 (ADIPOQ), were nominally associated with PCOS. However, they did not remain significant after correction for multiple testing, and none of the variants replicated in a sufficiently powered meta-analysis. Variants in the FBN3 gene (rs17202517 and rs73503752) were associated with smaller waist circumferences, and variant rs727428 in the SHBG gene was associated with lower sex hormone-binding globulin levels. Conclusion(s): Previously identified variants in candidate genes do not seem to be associated with PCOS risk. (c) 2013 by American Society for Reproductive Medicine. C1 [Pau, Cindy; Welt, Corrine Kolka] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Anesthesia, Boston, MA 02114 USA. RP Pau, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cta@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU National Institutes of Health [1R01HD065029, ADA 1-10-CT-57, 1 UL1 RR025758, M01-RR-01066] FX This work was supported by National Institutes of Health grants 1R01HD065029 (to C.K.W.), ADA 1-10-CT-57 (to C.K.W.), 1 UL1 RR025758 (Harvard Clinical and Translational Science Center), and M01-RR-01066 (National Center for Research Resources). NR 42 TC 10 Z9 10 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2013 VL 99 IS 6 BP 1774 EP 1778 DI 10.1016/j.fertnstert.2012.12.033 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 139VF UT WOS:000318612400048 PM 23375202 ER PT J AU Hilgendorf, KI Leshchiner, ES Nedelcu, S Maynard, MA Calo, E Ianari, A Walensky, LD Lees, JA AF Hilgendorf, Keren I. Leshchiner, Elizaveta S. Nedelcu, Simona Maynard, Mindy A. Calo, Eliezer Ianari, Alessandra Walensky, Loren D. Lees, Jacqueline A. TI The retinoblastoma protein induces apoptosis directly at the mitochondria SO GENES & DEVELOPMENT LA English DT Article DE MOMP; apoptosis; cancer; pRB; retinoblastoma protein ID TUMOR-SUPPRESSOR PROTEIN; NF-KAPPA-B; BCL-2 FAMILY; CELL-DEATH; MEMBRANE PERMEABILIZATION; PROAPOPTOTIC FUNCTION; RB FUNCTIONS; DNA-DAMAGE; BAX; P53 AB The retinoblastoma protein gene RB-1 is mutated in one-third of human tumors. Its protein product, pRB ( retinoblastoma protein), functions as a transcriptional coregulator in many fundamental cellular processes. Here, we report a nonnuclear role for pRB in apoptosis induction via pRB's direct participation in mitochondrial apoptosis. We uncovered this activity by finding that pRB potentiated TNF alpha-induced apoptosis even when translation was blocked. This proapoptotic function was highly BAX- dependent, suggesting a role in mitochondrial apoptosis, and accordingly, a fraction of endogenous pRB constitutively associated with mitochondria. Remarkably, we found that recombinant pRB was sufficient to trigger the BAX- dependent permeabilization of mitochondria or liposomes in vitro. Moreover, pRB interacted with BAX in vivo and could directly bind and conformationally activate BAX in vitro. Finally, by targeting pRB specifically to mitochondria, we generated a mutant that lacked pRB's classic nuclear roles. This mito-tagged pRB retained the ability to promote apoptosis in response to TNF alpha and also additional apoptotic stimuli. Most importantly, induced expression of mito-tagged pRB in Rb-/-; p53(-/-) tumors was sufficient to block further tumor development. Together, these data establish a nontranscriptional role for pRB in direct activation of BAX and mitochondrial apoptosis in response to diverse stimuli, which is profoundly tumor-suppressive. C1 [Hilgendorf, Keren I.; Nedelcu, Simona; Maynard, Mindy A.; Calo, Eliezer; Ianari, Alessandra; Lees, Jacqueline A.] MIT, David H Koch Inst Integrat Canc Res MIT, Cambridge, MA 02139 USA. [Hilgendorf, Keren I.; Nedelcu, Simona; Calo, Eliezer; Lees, Jacqueline A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Leshchiner, Elizaveta S.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Leshchiner, Elizaveta S.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Leshchiner, Elizaveta S.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02215 USA. [Leshchiner, Elizaveta S.; Walensky, Loren D.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Leshchiner, Elizaveta S.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ianari, Alessandra] Univ Roma La Sapienza, Dept Mol Med, I-00161 Rome, Italy. RP Lees, JA (reprint author), MIT, David H Koch Inst Integrat Canc Res MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jalees@mit.edu FU NCI/NIH; NSF; D.H. Koch Graduate Fellowship FX We thank E. Knudsen for providing the RAT16 parental and LP-RB-inducible cell lines, A. Letai for wild-type and Bax-/-/Bak-/- MEFs, S. Lowe for human Rb shRNA, and M. Hemann for rodent Rb shRNA. We also thank the members of the Lees laboratory for input during the study and manuscript preparation. This work was supported by an NCI/NIH grant to J.A.L., who is a Ludwig Scholar at MIT. K.I.H. was supported by an NSF predoctoral fellowship and D.H. Koch Graduate Fellowship. NR 57 TC 31 Z9 33 U1 2 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 2013 VL 27 IS 9 BP 1003 EP 1015 DI 10.1101/gad.211326.112 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 141BQ UT WOS:000318700800007 PM 23618872 ER PT J AU Friedman, DJ Upadhyay, GA Altman, RK Orencole, M Barrett, CD Mela, T Heist, EK Singh, JP AF Friedman, Daniel J. Upadhyay, Gaurav A. Altman, Robert K. Orencole, Mary Barrett, Conor D. Mela, Theofanie Heist, E. Kevin Singh, Jagmeet P. TI The anatomic and electrical location of the left ventricular lead predicts ventricular arrhythmia in cardiac resynchronization therapy SO HEART RHYTHM LA English DT Article DE Congestive heart failure; Heart failure; Cardiac resynchronization therapy; Lead; Ventricular tachycardia; Ventricular fibrillation ID DEFIBRILLATOR IMPLANTATION TRIAL; HEART-FAILURE PATIENTS; BUNDLE-BRANCH BLOCK; REVERSE; ACTIVATION; RISK; TACHYARRHYTHMIAS; DYSSYNCHRONY; STIMULATION; MORTALITY AB BACKGROUND Both anatomic and electrical locations of the left ventricular (LV) lead have been identified as important predictors of clinical outcomes in cardiac resynchronization therapy (CRT). The impact of LV lead location on incident device-treated ventricular arrhythmia (VA), however, is not well understood. OBJECTIVE To assess the relationship between electrical and anatomic LV lead location and device treated VAs in CRT. METHODS Sixty-nine patients undergoing CRT implantation for standard indications were evaluated. Anatomic LV lead location was assessed by means of coronary venography and chest radiography and categorized as apical or nonapical. Electrical LV lead location was assessed by LV electrical delay (LVLED) and was calculated as the time between the onset of the native QRS on the surface electrocardiogram and sensed signal on the LV lead during implantation and corrected for native QRS. Incident appropriate device-treated VA was assessed via device interrogation. RESULTS Apical lead placement was an independent predictor of VAs (hazard ratio 5.29; 95% confidence interval 1.69-16.5; P = .004). Among patients with a nonapical lead, LVLED <50% native QRS was an independent predictor of VAs (hazard ratio 6.90; 95% confidence interval 1.53-31.1; P = .012). Those with a nonapical lead and LVLED >= 50% native QRS were at substantiaily lower risk for first incident and recurrent VAs when compared to all other patients. CONCLUSIONS The apical lead position is associated with an increased risk of VAs in CRT patients. Among patients with a nonapical lead position, an LVLED of <50% of the native QRS is associated with an increased risk of VAs. C1 [Friedman, Daniel J.; Upadhyay, Gaurav A.; Altman, Robert K.; Orencole, Mary; Barrett, Conor D.; Mela, Theofanie; Heist, E. Kevin; Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Altman, Robert/0000-0002-1612-3561; Friedman, Daniel /0000-0001-5791-1954 FU Biotronik; Sorin; St Jude Medical; Boston Scientific; Medtronic; Boston; Scientific; CardioInsight; Thoratec; Biosense Webster FX Dr Heist has received honoraria from Biotronik, Boston Scientific, Sorin, and St Jude Medical; research grants from Biotronik, Sorin, and St Jude Medical; and consulting fees from Boston Scientific, Sorin, and St Jude Medical. Dr Me la has received honoraria from Boston Scientific, Medtronic, and St Jude Medical and consulting fees from St Jude Medical. Ms Orencole has received honoraria from Boston Scientific. Dr Singh has received research grants from St Jude Medical, Medtronic, Boston Scientific, and Biotronik; consulting fees from Boston Scientific, Biotronik, St Jude Medical, Medtronic, CardioInsight, Thoratec, and Biosense Webster; and honoraria from Medtronic, Biotronik, Guidant, St Jude Medical, and Sorin. NR 35 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAY PY 2013 VL 10 IS 5 BP 668 EP 675 DI 10.1016/j.hrthm.2012.12.025 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 140QY UT WOS:000318671200016 PM 23274368 ER PT J AU Rogers, DJ Hartnick, CJ AF Rogers, Derek J. Hartnick, Christopher J. TI Endoscopic CO2 laser laryngofissure in pediatric laryngotracheal reconstruction SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Laryngotracheal reconstruction; Laryngofissure; Pediatric airway; Endoscopic carbon dioxide laser; Anterior commissure; Pediatric voice ID AIRWAY RECONSTRUCTION; VOICE; OUTCOMES AB Anterior laryngofissure is often needed to provide excellent visualization of the posterior cricoid lamina during pediatric laryngotracheal reconstruction. Focus has shifted from survival and decannulation outcomes to postoperative voice outcomes as surgical techniques continue to improve. Surgeons must perform the laryngofissure extremely precisely to avoid damage to the true vocal folds and ensure proper reapproximation of the anterior commissure. Endoscopic CO2 laser laryngofissure represents a novel technique to divide the anterior commissure and facilitate its accurate reapproximation. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Rogers, Derek J.; Hartnick, Christopher J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Hartnick, CJ (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD MAY PY 2013 VL 77 IS 5 BP 850 EP 853 DI 10.1016/j.ijporl.2013.01.015 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 136SP UT WOS:000318384000046 PM 23394794 ER PT J AU Frazier, AL Rosenberg, SM AF Frazier, A. Lindsay Rosenberg, Shoshana M. TI Preadolescent and Adolescent Risk Factors for Benign Breast Disease SO JOURNAL OF ADOLESCENT HEALTH LA English DT Review ID PROLIFERATIVE EPITHELIAL DISORDERS; CANCER RISK; ALCOHOL-CONSUMPTION; PREMENOPAUSAL WOMEN; NURSES HEALTH; UNITED-STATES; BODY FATNESS; YOUNG-WOMEN; EARLY-LIFE; DIET AB Purpose: It is well established that exposures during childhood and adolescence affect breast cancer risk much later in life. Recently, studies have begun to evaluate whether early life exposures might also impact the risk of developing benign breast disease (BBD). A diagnosis of proliferative BBD independent of other breast cancer risk factors also increases the subsequent risk of breast cancer; therefore, understanding how to decrease the incidence of BBD may have important implications for primary breast cancer prevention. Methods: We reviewed several studies from prospective cohort studies that have investigated the relationship between risk factors during childhood and adolescence, such as anthropometric and reproductive characteristics as well as diet and other behaviors, and subsequent risk of BBD. Results: Higher intake of vegetable oils, nuts, vitamin E, and fiber and lower consumption of animal fat, red meat, and alcohol are associated with reduced risk of BBD. Childhood weight and adolescent body mass index are inversely associated with BBD risk, whereas a greater peak height velocity during adolescence is associated with a higher risk of BBD. There was no association between age of menarche and risk of BBD. Conclusion: Early life exposures and behaviors appear to impact BBD risk. The current body of evidence further supports the importance of a life-course approach to breast cancer prevention. (C) 2013 Society for Adolescent Health and Medicine. All rights reserved. C1 [Frazier, A. Lindsay] Harvard Univ, Sch Med, Div Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Rosenberg, Shoshana M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Frazier, AL (reprint author), Harvard Univ, Sch Med, Div Pediat Oncol, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM lindsay_frazier@dfci.harvard.edu FU NIH [R25 CA92203] FX Shoshana Rosenberg is funded by NIH R25 CA92203. NR 40 TC 5 Z9 6 U1 2 U2 17 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 MAY PY 2013 VL 52 IS 5 SU S BP S36 EP S40 DI 10.1016/j.jadohealth.2013.01.007 PG 5 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 140UQ UT WOS:000318681800006 PM 23601609 ER PT J AU Shank, ES Sheridan, RL Ryan, CM Keaney, TJ Martyn, JAJ AF Shank, Erik S. Sheridan, Robert L. Ryan, Colleen M. Keaney, Timothy J. Martyn, J. A. Jeevendra TI Hemodynamic Responses to Dexmedetomidine in Critically Injured Intubated Pediatric Burned Patients: A Preliminary Study SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID MECHANICAL VENTILATION; POSTTRAUMATIC-STRESS; INDUCED HYPERALGESIA; CLINICAL-USES; MAJOR BURNS; CHILDREN; SEDATION; PAIN; HYPERTENSION; PHARMACOLOGY AB Because of ineffectiveness and tolerance to benzodiazepines and opioids developing with time, drugs acting via other receptor systems (eg, alpha-2 agonists) have been advocated in burn patients to improve sedation and analgesia. This study in severely burned pediatric subjects examined the hemodynamic consequences of dexmedetomidine (Dex) administration. Eight intubated patients with >= 20 to 79% TBSA burns were studied between 7 and 35 days after injury. After baseline measurements of mean arterial blood pressure and heart rhythm were taken, each patient received a 1.0 mu g/kg bolus of Dex followed by an ascending dose infusion protocol (0.7-2.5 mu g/kg/hr), with each dose administered for 15 minutes. There was significant hypotension (27 +/- 7.5%, average drop in mean arterial pressure [MAP] +/- SD), and a decrease in heart rate (HR; 19% +/- 7, average drop in HR +/- SD). The average HR decreased from 146 beats per minute to 120. No bradycardia (HR < 60) or heart blocks were observed. In three patients, the MAP decreased to < 50 mm Hg with the bolus dose of Dex. Of the remaining five patients, three patients completed the study receiving the highest infusion dose of Dex (2.5 mu g/kg/hr), whereas in 2 patients the infusion part of the study was begun, but the study was stopped due to persistent hypotension (MAP < 50 mm Hg). These observations indicate that a bolus dose of Dex (1.0 mu g/kg for 10 minutes) and high infusion rates may require fluid resuscitation or vasopressor support to maintain normotension in critically injured pediatric burn patients. (J Burn Care Res 2013;34:311-317) C1 [Shank, Erik S.; Martyn, J. A. Jeevendra] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Shank, Erik S.; Sheridan, Robert L.; Ryan, Colleen M.; Keaney, Timothy J.; Martyn, J. A. Jeevendra] Shriners Hosp Children, Boston, MA USA. [Shank, Erik S.; Sheridan, Robert L.; Ryan, Colleen M.; Martyn, J. A. Jeevendra] Harvard Univ, Sch Med, Boston, MA USA. [Sheridan, Robert L.; Ryan, Colleen M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Shank, ES (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Gray Jackson 409,55 Fruit St, Boston, MA 02114 USA. FU Shriners Hospitals for Children(R) FX Supported by the Shriners Hospitals for Children (R). NR 41 TC 4 Z9 4 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2013 VL 34 IS 3 BP 311 EP 317 DI 10.1097/BCR.0b013e318257d94a PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 139XO UT WOS:000318618600016 PM 22929526 ER PT J AU Fuzaylov, G AF Fuzaylov, Gennadiy TI Burn Victim: Story of a Survivor SO JOURNAL OF BURN CARE & RESEARCH LA English DT Letter ID GARLIC BURNS C1 [Fuzaylov, Gennadiy] Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Fuzaylov, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Burn Children, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2013 VL 34 IS 3 BP E213 EP E213 DI 10.1097/BCR.0b013e3182642b5c PG 1 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 139XO UT WOS:000318618600012 PM 23128137 ER PT J AU Ryan, CM Schneider, JC Kazis, LE Lee, A Li, NC Hinson, M Bauk, H Peck, M Meyer, WJ Palmieri, T Pidcock, FS Reilly, D Tompkins, RG AF Ryan, Colleen M. Schneider, Jeffrey C. Kazis, Lewis E. Lee, Austin Li, Nien-chen Hinson, Michelle Bauk, Helena Peck, Michael Meyer, Walter J., III Palmieri, Tina Pidcock, Frank S. Reilly, Debra Tompkins, Ronald G. CA Multi-Ctr Benchmarking Study Grp TI Benchmarks for Multidimensional Recovery After Burn Injury in Young Adults: The Development, Validation, and Testing of the American Burn Association/Shriners Hospitals for Children Young Adult Burn Outcome Questionnaire SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; HEALTH SCALE-BRIEF; FOR-CHILDREN; TERM; SURVIVORS; CONSTRUCTION; PERCEPTIONS; PREDICTORS; PROGRAM; VERSION AB Although data exist on burn survival, there are little data on long-term burn recovery. Patient-centered health outcomes are useful in monitoring and predicting recovery and evaluating treatments. An outcome questionnaire for young adult burn survivors was developed and tested. This 5-year (2003-2008) prospective, controlled, multicenter study included burned and nonburned adults ages 19 to 30 years. The Young Adult Burn Outcome Questionnaires were completed at initial contact, 10 days, and 6 and 12 months. Factor analysis established construct validity. Reliability assessments used Cronbach alpha and test-retest. Recovery patterns were investigated using generalized linear models, with generalized estimating equations using mixed models and random effects. Burned (n = 153) and nonburned subjects (n = 112) completed 620 questionnaires (47 items). Time from injury to first questionnaire administration was 157 +/- 36 days (mean +/- SEM). Factor analysis included 15 factors: Physical Function, Fine Motor Function, Pain, Itch, Social Function Limited by Physical Function, Perceived Appearance, Social Function Limited by Appearance, Sexual Function, Emotion, Family Function, Family Concern, Satisfaction With Symptom Relief, Satisfaction With Role, Work Reintegration, and Religion. Cronbach alpha ranged from 0.72 to 0.92, with 11 scales >0.8. Test-retest reliability ranged from 0.29 to 0.94, suggesting changes in underlying health status after burns. Recovery curves in five domains, Itch, Perceived Appearance, Social Function Limited by Appearance, Family Concern, and Satisfaction with Symptom Relief, remained below the reference group at 24 months. The Young Adult Burn Outcome Questionnaire is a reliable and valid instrument for multidimensional functional outcomes assessment. Recovery in some domains was incomplete. (J Burn Care Res 2013;34:e121-e142) C1 [Ryan, Colleen M.; Lee, Austin; Tompkins, Ronald G.] Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. [Ryan, Colleen M.; Schneider, Jeffrey C.; Hinson, Michelle; Bauk, Helena; Meyer, Walter J., III; Palmieri, Tina; Tompkins, Ronald G.] Shriners Hosp Children, Sacramento, CA USA. [Ryan, Colleen M.; Schneider, Jeffrey C.; Tompkins, Ronald G.] Harvard Univ, Med Sch, Cambridge, MA 02138 USA. [Schneider, Jeffrey C.] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Kazis, Lewis E.; Li, Nien-chen] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Peck, Michael] Univ Arizona, Coll Med, Dept Surg, Phoenix, AZ USA. [Meyer, Walter J., III] Univ Texas Med Branch, Dept Psychiat, Galveston, TX 77555 USA. [Palmieri, Tina] Univ Calif Davis, Dept Surg, Davis, CA 95616 USA. [Pidcock, Frank S.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD 21218 USA. [Pidcock, Frank S.] Kennedy Krieger Inst, Baltimore, MD USA. [Reilly, Debra] Univ Nebraska, Div Plast & Reconstruct Surg, Omaha, NE 68182 USA. RP Ryan, CM (reprint author), Massachusetts Gen Hosp, Bigelow 1302,55 Fruit St, Boston, MA 02114 USA. OI Kazis, Lewis/0000-0003-1800-5849 FU American Burn Association; Shriners Hospitals for Children; Fraser Fund at the Massachusetts General Hospital FX This work was supported in part by the author's institutions, the American Burn Association, the Shriners Hospitals for Children, and the Fraser Fund at the Massachusetts General Hospital. NR 54 TC 15 Z9 16 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2013 VL 34 IS 3 BP E121 EP E142 DI 10.1097/BCR.0b013e31827e7ecf PG 22 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 139XO UT WOS:000318618600001 PM 23511284 ER PT J AU Turcu, AF Erickson, BJ Lin, E Guadalix, S Schwartz, K Scheithauer, BW Atkinson, JLD Young, WF Jr, AF Turcu, Adina F. Erickson, Bradley J. Lin, Eleanor Guadalix, Sonsoles Schwartz, Kara Scheithauer, Bernd W. Atkinson, John L. D. Young, William F., Jr. TI Pituitary Stalk Lesions: The Mayo Clinic Experience SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID XANTHOMA-DISSEMINATUM; METASTASES; SARCOIDOSIS; INVOLVEMENT; GLAND; MR AB Context: Pituitary stalk lesions have various etiologies, often not clinically apparent. Pathological samples from these lesions are rarely obtained, because of the critical location and function of the hypophyseal stalk. Objectives: The purpose of this study was to characterize the etiological spectrum of pituitary stalk lesions seen at Mayo Clinic Rochester over 20 years and to determine whether specific magnetic resonance imaging (MRI) characteristics could provide clinician guidance with regard to the etiology of infundibular lesions. Design: Aretrospective review of patients with pituitary stalk lesions seen at Mayo Clinic Rochester between 1987 and 2006 was conducted. Demographic, clinical presentation, imaging, laboratory, operative, and pathology data were reviewed and are reported using descriptive statistics. Results: Of the 152 pituitary stalk lesions included, 49 (32%) were neoplastic, 30 (20%) were inflammatory, 13 (9%) were congenital anomalies, and 60 (39%) were of unclear etiology. Diabetes insipidus was diagnosed in 43 (28%) of the 152 patients, and 49 (32%) patients had at least one anterior pituitary hormone deficit. Secondary hypogonadism was the most common endocrine deficiency. Eleven of 13 congenital lesions were round in appearance and 5 of 7 patients with neurosarcoidosis confirmed by pathology had a uniformly thickened pituitary stalk on MRI. There were no statistically significant correlations between hypopituitarism and the pattern of enhancement or size of the lesion. Conclusions: Findings on MRI remain key in guiding the diagnosis of pituitary stalk lesions, particularly when used in conjunction with other clinical clues. There are no good imaging predictors for hypopituitarism, making clinical evaluation of all patients with pituitary stalk lesions crucial. (J Clin Endocrinol Metab 98: 1812-1818, 2013) C1 [Turcu, Adina F.; Young, William F., Jr.] Mayo Clin Rochester, Div Endocrinol, Rochester, MN 55905 USA. [Erickson, Bradley J.; Schwartz, Kara] Mayo Clin Rochester, Dept Radio, Rochester, MN 55905 USA. [Scheithauer, Bernd W.] Mayo Clin Rochester, Dept Anat Pathol, Rochester, MN 55905 USA. [Atkinson, John L. D.] Mayo Clin Rochester, Dept Neurol Surg, Rochester, MN 55905 USA. [Lin, Eleanor] Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. [Guadalix, Sonsoles] Univ Hosp 12 Octubre, Madrid 28041, Spain. RP Young, WF Jr, (reprint author), Mayo Clin Rochester, Div Endocrinol Diabet Metab Nutr & Internal Med, 200 1st St Southwest, Rochester, MN 55905 USA. EM young.william@mayo.edu FU Mayo Clinic FX Funding for this study was provided by the Mayo Clinic. NR 17 TC 11 Z9 15 U1 0 U2 9 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 MAY PY 2013 VL 98 IS 5 BP 1812 EP 1818 DI 10.1210/jc.2012-4171 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 140WX UT WOS:000318688200038 PM 23533231 ER PT J AU Faje, AT Karim, L Taylor, A Lee, H Miller, KK Mendes, N Meenaghan, E Goldstein, MA Bouxsein, ML Misra, M Klibanski, A AF Faje, Alexander T. Karim, Lamya Taylor, Alex Lee, Hang Miller, Karen K. Mendes, Nara Meenaghan, Erinne Goldstein, Mark A. Bouxsein, Mary L. Misra, Madhusmita Klibanski, Anne TI Adolescent Girls With Anorexia Nervosa Have Impaired Cortical and Trabecular Microarchitecture and Lower Estimated Bone Strength at the Distal Radius SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID QUANTITATIVE COMPUTED-TOMOGRAPHY; PANEL VOLUME CT; HR-PQCT; FINITE-ELEMENT; POSTMENOPAUSAL WOMEN; FRACTURES; GROWTH; CHILDREN; TIBIA; EPIDEMIOLOGY AB Context: Adolescents with anorexia nervosa (AN) have low areal bone mineral density (aBMD) at both cortical and trabecular sites, and recent data show impaired trabecular microarchitecture independent of aBMD. However, data are lacking regarding both cortical microarchitecture and bone strength assessment by finite element analysis (FEA) in adolescents with AN. Because microarchitectural abnormalities and FEA may predict fracture risk independent of aBMD, these data are important to obtain. Objective: Our objective was to compare both cortical and trabecular bone microarchitecture and FEA estimates of bone strength in adolescent girls with AN vs normal-weight controls. Design, Setting, and Subjects: We conducted a cross-sectional study at a clinical research center that included 44 adolescent girls (21 with AN and 23 normal-weight controls) 14 to 22 years old. Main Outcome Measures: We evaluated 1) aBMD (dual-energy x-ray absorptiometry) at the distal radius, lumbar spine, and hip, 2) cortical and trabecular microarchitecture at the ultradistal radius (high-resolution peripheral quantitative computed tomography), and 3) FEA-derived estimates of failure load at the ultradistal radius. Results: aBMD was lower in girls with AN vs controls at the lumbar spine and hip but not at the distal radius. Girls with AN had lower total (P < .0001) and trabecular volumetric BMD (P = .02) and higher cortical porosity (P = .03) and trabecular separation (P = .04). Despite comparable total cross-sectional area, trabecular area was higher in girls with AN (P = .04), and cortical area and thickness were lower (P = .002 and .02, respectively). FEA-estimated failure load was lower in girls with AN (P = .004), even after controlling for distal radius aBMD. Conclusions: Both cortical and trabecular microarchitecture are altered in adolescent girls with AN. FEA-estimated failure load is decreased, indicative of reduced bone strength. The finding of reduced cortical bone area in girls with AN is consistent with impaired cortical bone formation at the endosteum as a mechanism underlying these findings. (J Clin Endocrinol Metab 98: 1923-1929, 2013) C1 [Faje, Alexander T.; Taylor, Alex; Miller, Karen K.; Mendes, Nara; Meenaghan, Erinne; Bouxsein, Mary L.; Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp Children, Neuroendocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp Children, Ctr Biostat, Boston, MA 02114 USA. [Goldstein, Mark A.] Massachusetts Gen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Karim, Lamya; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, 55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org RI Mendes Estella, Nara/A-1469-2015 FU National Institutes of Health [5 UL1 RR025758, 2 RO1 DK062249]; Scanco Medical AG; [NIH/NCRR 1 S10 RR023405] FX This work was supported by National Institutes of Health Grants 5 UL1 RR025758 and 2 RO1 DK062249. We acknowledge funding from an equipment grant (NIH/NCRR 1 S10 RR023405).; Disclosure Summary: A. T. has received consultant fees from Scanco Medical AG. NR 38 TC 26 Z9 26 U1 0 U2 1 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 MAY PY 2013 VL 98 IS 5 BP 1923 EP 1929 DI 10.1210/jc.2012-4153 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 140WX UT WOS:000318688200052 PM 23509107 ER PT J AU Costa-Barbosa, FA Balasubramanian, R Keefe, KW Shaw, ND Al-Tassan, N Plummer, L Dwyer, AA Buck, CL Choi, JH Seminara, SB Quinton, R Monies, D Meyer, B Hall, JE Pitteloud, N Crowley, WF AF Costa-Barbosa, Flavia Amanda Balasubramanian, Ravikumar Keefe, Kimberly W. Shaw, Natalie D. Al-Tassan, Nada Plummer, Lacey Dwyer, Andrew A. Buck, Cassandra L. Choi, Jin-Ho Seminara, Stephanie B. Quinton, Richard Monies, Dorota Meyer, Brian Hall, Janet E. Pitteloud, Nelly Crowley, William F., Jr. TI Prioritizing Genetic Testing in Patients With Kallmann Syndrome Using Clinical Phenotypes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; GONADOTROPIN-RELEASING-HORMONE; PROKINETICIN RECEPTOR 2; OF-FUNCTION MUTATIONS; REPRODUCTIVE PHENOTYPES; CHARGE SYNDROME; 1 FGFR1; DEFICIENCY; GROWTH; KAL1 AB Context: The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening. Objective: The objective of the study was to determine which reproductive and nonreproductive phenotypes of KS subjects have implications for specific gene mutations. Subjects: Two hundred nineteen KS patients were studied: 151 with identified rare sequence variants (RSVs) in 8 genes known to cause KS (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) and 68 KS subjects who remain RSV negative for all 8 genes. Main Outcome Measures: Reproductive and nonreproductive phenotypes within each genetic group were measured. Results: Male KS subjects with KAL1 RSVs displayed the most severe reproductive phenotype with testicularvolumes(TVs) at presentation of 1.5 +/- 0.1 mL vs 3.7 +/- 0.3 mL, P<.05 vs all non-KAL1 probands. In both sexes, synkinesia was enriched but not unique to patients with KAL1 RSVs compared with KAL1-negative probands (43% vs 12%; P<.05). Similarly, dental agenesis and digital bone abnormalities were enriched in patients with RSVs in the FGF8/FGFR1 signaling pathway compared with all other gene groups combined (39% vs 4% and 23% vs 0%; P<.05, respectively). Hearing loss marked the probands with CHD7 RSVs (40% vs 13% in non-CHD7 probands; P<.05). Renal agenesis and cleft lip/palate did not emerge as statistically significant phenotypic predictors. Conclusions: Certain clinical features in men and women are highly associated with genetic causes of KS. Synkinesia (KAL1), dentalagenesis(FGF8/FGFR1), digital bony abnormalities(FGF8/FGFR1), and hearing loss (CHD7) can be useful for prioritizing genetic screening. C1 [Costa-Barbosa, Flavia Amanda; Balasubramanian, Ravikumar; Keefe, Kimberly W.; Shaw, Natalie D.; Plummer, Lacey; Buck, Cassandra L.; Choi, Jin-Ho; Seminara, Stephanie B.; Hall, Janet E.; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Costa-Barbosa, Flavia Amanda; Balasubramanian, Ravikumar; Keefe, Kimberly W.; Shaw, Natalie D.; Plummer, Lacey; Buck, Cassandra L.; Choi, Jin-Ho; Seminara, Stephanie B.; Hall, Janet E.; Crowley, William F., Jr.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Al-Tassan, Nada; Monies, Dorota; Meyer, Brian] King Faisal Special Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Dwyer, Andrew A.; Pitteloud, Nelly] CHU Vaudois, Endocrine Diabet & Metab Serv, CH-1011 Lausanne, Switzerland. [Quinton, Richard] Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. RP Crowley, WF (reprint author), Harvard Univ, Sch Med, Bartlett Hall Extens 511,55 Fruit St, Boston, MA 02114 USA. EM wcrowley@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Meyer, Brian/0000-0002-0388-9568; Shaw, Natalie/0000-0002-0847-9170; Hall, Janet/0000-0003-4644-3061 FU Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard University; National Institutes of Health [U54 HD028138, R01 HD15788, R01 HD056264, R01 HD42708] FX We thank all our patients, their families, and the collaborating physicians from across the world who facilitated our recruitment efforts and volunteered their time and energy to enable this study. We also thank Dr Ye-Ming Chan for helpful discussions on this manuscript. Biostatistical analysis was conducted with support from 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 work was supported by National Institutes of Health Grants U54 HD028138 and R01 HD15788 (to W.F.C.), R01 HD056264 (to N.P.), and R01 HD42708 (to J.E.H.). NR 45 TC 33 Z9 34 U1 0 U2 10 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 MAY PY 2013 VL 98 IS 5 BP E943 EP E953 DI 10.1210/jc.2012-4116 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 140WX UT WOS:000318688200020 PM 23533228 ER PT J AU Dean, JP Sprenger, CC Wan, JX Haugk, K Ellis, WJ Lin, DW Corman, JM Dalkin, BL Mostaghel, E Nelson, PS Cohen, P Montgomery, B Plymate, SR AF Dean, James P. Sprenger, Cynthia C. Wan, Junxiang Haugk, Kathleen Ellis, William J. Lin, Daniel W. Corman, John M. Dalkin, Bruce L. Mostaghel, Elahe Nelson, Peter S. Cohen, Pinchas Montgomery, Bruce Plymate, Stephen R. TI Response of the Insulin-Like Growth Factor (IGF) System to IGF-IR Inhibition and Androgen Deprivation in a Neoadjuvant Prostate Cancer Trial: Effects of Obesity and Androgen Deprivation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FACTOR RECEPTOR ANTIBODY; RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; PHASE-II; GLUCOSE-HOMEOSTASIS; TARGETED THERAPY; HORMONE-THERAPY; RESISTANCE; DOCETAXEL; EFFICACY AB Context: Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR). Objective: A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined. Design: Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone. Results: Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients. Conclusions: Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort. C1 [Dean, James P.; Mostaghel, Elahe; Nelson, Peter S.; Montgomery, Bruce] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. [Dean, James P.; Sprenger, Cynthia C.; Mostaghel, Elahe; Nelson, Peter S.; Montgomery, Bruce; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Wan, Junxiang; Cohen, Pinchas] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Haugk, Kathleen; Plymate, Stephen R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Ellis, William J.; Lin, Daniel W.; Corman, John M.; Dalkin, Bruce L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Corman, John M.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. RP Plymate, SR (reprint author), Univ Washington, Harborview Med Ctr, 325 9th Ave,Box 359625, Seattle, WA 98104 USA. EM splymate@u.washington.edu FU National Cancer Institute Pacific Northwest Prostate Cancer Specialized Program of Research Excellence (SPORE) [2 P50 CA 097186-06 Project 4]; Department of Veterans Affairs; Department of Defense Prostate Cancer Research Program [W81XWH-07-1-0159]; University of California Los Angeles Prostate Cancer SPORE [P50 CA92131]; [PO1 CA85859] FX This clinical trial was supported by the National Cancer Institute Pacific Northwest Prostate Cancer Specialized Program of Research Excellence (SPORE) (2 P50 CA 097186-06 Project 4), PO1 CA85859, and the Department of Veterans Affairs (to S.R.P.). Laboratory data analyses were supported by Department of Defense Prostate Cancer Research Program (W81XWH-07-1-0159; to J.P.D.), PO1 CA85859 and the Department of Veterans Affairs (to S.R.P.), and the University of California Los Angeles Prostate Cancer SPORE (P50 CA92131). NR 46 TC 10 Z9 10 U1 0 U2 1 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 MAY PY 2013 VL 98 IS 5 BP E820 EP E828 DI 10.1210/jc.2012-3856 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 140WX UT WOS:000318688200002 PM 23533230 ER PT J AU Herrick, BW Wallaert, JB Eisner, BH Pais, VM AF Herrick, Benjamin W. Wallaert, Jessica B. Eisner, Brian H. Pais, Vernon M., Jr. TI Insurance Status, Stone Composition, and 24-Hour Urine Composition SO JOURNAL OF ENDOUROLOGY LA English DT Article ID SOCIOECONOMIC-STATUS; KIDNEY-STONES; CALCIUM-PHOSPHATE; ANIMAL PROTEIN; RISK; SUPERSATURATION; NEPHROLITHIASIS; OXALATE; HYPERURICOSURIA; UROLITHIASIS AB Purpose: We examined the stone composition, 24-hour urinary risk factors, and insurance status in patients evaluated in two regional stone clinics to further investigate the relationship between the socioeconomic status and kidney stone formation. Materials and Methods: We performed a retrospective review of stone formers who completed a 24-hour urinalysis as part of a metabolic evaluation for nephrolithiasis. Insurance status was determined by billing records and those with state-assisted insurance (SAI) were compared to patients with private insurance (PI). Multivariate analyses were performed adjusting for known risk factors for stones. Results: Three hundred forty-six patients were included. Patients with SAI (16%) were significantly more likely to be female (55% vs. 38%, p = 0.026) and younger (43.5 vs. 49.2, p = 0.003). Among those with stone composition data (n = 200), SAI patients were as likely to form calcium phosphate (CaPhos) as calcium oxalate (CaOx) stones (46.9% vs. 31.3%, p = 0.44). PI patients were significantly less likely to form CaPhos than CaOx stones (10.1% vs. 77.4%, p < 0.001). On multivariate analysis, among those with calcium stones, the odds of forming CaPhos stones over CaOx stones were ten times higher among SAI patients compared to PI, odds ratio 10.2 (95% CI 3.6, 28.6, p < 0.001). Further, patients with SAI had significantly higher urine sodium, pH, and supersaturation of CaPhos, and a lower supersaturation of uric acid compared to patients with PI. Conclusions: SAI was associated with a greater likelihood of a CaPhos stone composition and increased urinary risk factors for CaPhos stones. These findings may reflect dietary or other unmeasured differences, and have important implications for resource allocation and counseling, as treatment may differ for these groups. C1 [Herrick, Benjamin W.; Pais, Vernon M., Jr.] Dartmouth Hitchcock Med Ctr, Dept Surg, Div Urol, Lebanon, NH 03756 USA. [Wallaert, Jessica B.] Dartmouth Inst, Hanover, NH USA. [Eisner, Brian H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Herrick, BW (reprint author), Dartmouth Hitchcock Med Ctr, Dept Surg, Div Urol, Ste 5B,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM benjamin.w.herrick@hitchcock.org NR 30 TC 1 Z9 1 U1 1 U2 33 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD MAY PY 2013 VL 27 IS 5 BP 652 EP 656 DI 10.1089/end.2012.0490 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 138ZX UT WOS:000318552100022 PM 23428069 ER PT J AU Gershman, B Eisner, BH Sheth, S Sacco, DE AF Gershman, Boris Eisner, Brian H. Sheth, Sonali Sacco, Dianne E. TI Ureteral Stenting and Retrograde Pyelography in the Office: Clinical Outcomes, Cost Effectiveness, and Time Savings SO JOURNAL OF ENDOUROLOGY LA English DT Article ID LOCAL-ANESTHESIA; FLEXIBLE CYSTOSCOPY; URETEROSCOPY; REMOVAL; PAINFUL AB Objectives: To examine the clinical outcomes and cost-effectiveness of endourologic procedures performed in the office using standard fluoroscopy and topical anesthesia. Methods: We performed a retrospective review of all patients who underwent primary ureteral stent placement, ureteral stent exchange, or ureteral catheterization with retrograde pyeolography or Bacillus Calmette-Guerin (BCG) instillation under fluoroscopic guidance in the office. For an evaluation of potential time savings, we compared this to a cohort of similar procedures performed in the operating room during the same time period. Results: Procedures were attempted in 65 renal units in 38 patients (13 male, 25 female) with a mean age of 62.2 years (range 29.1-95.4 years). Primary ureteral stent placement was successful in 23/24 (95.8%) renal units. Ureteral stent exchange was successful in 19/22 (86.4%) renal units. Ureteral catheterization with retrograde pyelography or BCG instillation was successful in 19/19 (100%) renal units. The total cost savings for the 38 patients in this study, including excess cost from failure in the office, was approximately $91,496, with an average cost savings of $1,551 per procedure. Office-based procedures were associated with a nearly three-fold reduction in total hospital time as a result of reduced periprocedure waiting times. Conclusions: Ureteral stent placement, ureteral stent exchange, and ureteral catheterization can be performed safely and effectively in the office in both men and women. This avoids general anesthesia and provides significant savings of time and cost for both patients and the health care system. C1 [Gershman, Boris; Eisner, Brian H.; Sheth, Sonali; Sacco, Dianne E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Sacco, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM dsacco@partners.org NR 17 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD MAY PY 2013 VL 27 IS 5 BP 662 EP 666 DI 10.1089/end.2012.0644 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 138ZX UT WOS:000318552100024 PM 23638674 ER PT J AU Hageman, MGH Becker, SJE Bot, AGJ Guitton, T Ring, D AF Hageman, Michiel G. H. Becker, Stephanie J. E. Bot, Arjan G. J. Guitton, Thierry Ring, David CA Sci Variation Grp TI Variation in Recommendation for Surgical Treatment for Compressive Neuropathy SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Carpal tunnel syndrome; decision making; electrodiagnostic testing; surgical treatment; peripheral nerve ID COMPENSATION; SURGERY; INJURY; CLAIMS; WORK; HAND AB Purpose It is our impression that there is substantial, unexplained variation in hand surgeon recommendations for treatment of peripheral mononeuropathy. We tested the null hypothesis that specific patient and provider factors do not influence recommendations for surgery. Methods Using a web-based survey, hand surgeons recommended surgical or nonsurgical treatment for patients in 2 different scenarios. Six elements of the first scenario (symptoms, circumstances, mindset, diagnosis, objective testing, and expectations) had 2 possibilities that were each independently and randomly assigned to each rater. For the second scenario, 2 different scenarios were randomly assigned to each rater. Multivariable logistic regression sought factors associated with a recommendation for surgery. Results A total of 186 surgeons of the Science of Variation Group completed a survey regarding recommendation of surgery for 2 different patients based on clinical scenarios. Recommendations for surgery did not vary significantly according to provider characteristics. For the various elements in scenario 1, recommendation for surgery was more likely for patients who were self-employed and continued to work and who had objective electrodiagnostic abnormalities. For the 2 vignettes used in scenario 2, a recommendation for surgery was associated with abnormal electrophysiology. Conclusions The findings of this study suggest that at least in a survey setting surgeons prefer to offer peripheral nerve decompression to patients with abnormal electrophysiology, particularly those with effective coping strategies. C1 [Hageman, Michiel G. H.; Becker, Stephanie J. E.; Bot, Arjan G. J.; Guitton, Thierry; Ring, David; Sci Variation Grp] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014; Fernandes, C/F-9839-2012; Calcagni, Maurizio/C-9769-2012; OI Fernandes, C/0000-0003-0146-6091; Calcagni, Maurizio/0000-0003-4372-0561; Kennedy, Stephen/0000-0001-8177-4988; Guitton, Thierry/0000-0002-2599-1985; Goldfarb, Charles/0000-0001-9672-8853; Kaplan, F. Thomas D./0000-0002-0348-507X NR 12 TC 2 Z9 2 U1 1 U2 13 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 MAY PY 2013 VL 38A IS 5 BP 856 EP 862 DI 10.1016/j.jhsa.2013.02.008 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 139KH UT WOS:000318581100003 PM 23561726 ER PT J AU Neuhaus, V Ring, DC AF Neuhaus, Valentin Ring, David C. TI Latent Class Analysis SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID LOW-BACK-PAIN; MUSCULOSKELETAL PAINS; POPULATION; FRACTURES; PATTERNS; CLASSIFICATION; VALIDATION; ARTHRITIS; INJURY C1 [Neuhaus, Valentin; Ring, David C.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 41 TC 3 Z9 3 U1 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2013 VL 38A IS 5 BP 1018 EP 1020 DI 10.1016/j.jhsa.2013.01.024 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 139KH UT WOS:000318581100028 PM 23474164 ER PT J AU Neuhaus, V Nagy, L Jupiter, JB AF Neuhaus, Valentin Nagy, Ladislav Jupiter, Jesse B. TI Bone Loss in the Hand SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article ID PROXIMAL INTERPHALANGEAL JOINT; FRACTURE-DISLOCATIONS; SOFT-TISSUE; FREE FLAP; RECONSTRUCTION; FINGER; ARTHROPLASTY; GRAFT; DEFECTS; TRANSPLANTATION AB Traumatic bone loss in hand surgery is challenging for the patient as well as the doctor. Whereas the patient is threatened with a possible amputation or severe disability, the hand surgeon focuses on reconstruction, restoration of the function, bony union, and appearance of the injured hand. Both are confronted with a long-standing and staged treatment coupled with a high risk of complications. This review encompasses the classifications and treatment options of bone loss in hands. The optimal treatment is still prevention of the trauma itself. (J Hand Surg 2013;38A:1032-1039. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Univ Zurich, Hand Serv, Balgrist Hosp, Zurich, Switzerland. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM jjupiter1@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 36 TC 1 Z9 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2013 VL 38A IS 5 BP 1032 EP 1039 DI 10.1016/j.jhsa.2013.02.026 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 139KH UT WOS:000318581100030 PM 23618459 ER PT J AU Karimi, M Avci, P Mobasseri, R Hamblin, MR Naderi-Manesh, H AF Karimi, Mahdi Avci, Pinar Mobasseri, Rezvan Hamblin, Michael R. Naderi-Manesh, Hossein TI The novel albumin-chitosan core-shell nanoparticles for gene delivery: preparation, optimization and cell uptake investigation SO JOURNAL OF NANOPARTICLE RESEARCH LA English DT Article DE Albumin; Chitosan; Nanoparticle; Gene delivery; Optimization ID BOX-BEHNKEN DESIGN; IN-VITRO; DRUG-DELIVERY; ELECTROSPUN NANOFIBERS; DESOLVATION PROCESS; DNA NANOPARTICLES; HSA-NANOPARTICLES; THERAPY; SYSTEMS; SURFACE AB Natural polymers and proteins such as chitosan (CS) and albumin (Alb) have recently attracted much attention both in drug delivery and gene delivery. The underlying rationale is their unique properties such as biodegradability, biocompatibility and controlled release. This study aimed to prepare novel albumin-chitosan-DNA (Alb-CS-DNA) core-shell nanoparticles as a plasmid delivery system and find the best conditions for their preparation. Phase separation method and ionic interaction were used for preparation of Alb nanoparticles and Alb-CS-DNA core-shell nanoparticles, respectively. The effects of three important independent variables (1) CS/Alb mass ratio, (2) the ratios of moles of the amine groups of cationic polymers to those of the phosphate groups of DNA (N/P ratio), and (3) Alb concentration, on the nanoparticle size and loading efficiency of the plasmid were investigated and optimized through Box-Behnken design of response surface methodology (RSM). The optimum conditions were found to be CS/Alb mass ratio = 3, N/P ratio = 8.24 and Alb concentration = 0.1 mg/mL. The most critical factors for the size of nanoparticles and loading efficiency were Alb concentration and N/P ratio. The optimized nanoparticles had an average size of 176 +/- 3.4 nm and loading efficiency of 80 +/- 3.9 %. Cytotoxicity experiments demonstrated that the prepared nanoparticles were not toxic. The high cellular uptake of nanoparticles (similar to 85 %) was shown by flow cytometry and fluorescent microscopy. C1 [Karimi, Mahdi; Mobasseri, Rezvan; Naderi-Manesh, Hossein] Tarbiat Modares Univ, Dept Nanobiotechnol, Fac Biol Sci, Tehran, Iran. [Karimi, Mahdi; Avci, Pinar; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Karimi, Mahdi; Avci, Pinar; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02119 USA. [Naderi-Manesh, Hossein] Tarbiat Modares Univ, Dept Biophys, Fac Biol Sci, Tehran, Iran. RP Naderi-Manesh, H (reprint author), Tarbiat Modares Univ, Dept Biophys, Fac Biol Sci, Tehran, Iran. EM naderman@modares.ac.ir OI Karimi, Mahdi/0000-0002-7977-3940; Hamblin, Michael/0000-0001-6431-4605 FU nano initiative; Tarbiat Modares University; US NIH [R01A1050875] FX This work was partially supported by nano initiative and Tarbiat Modares University. MR Hamblin was supported by US NIH grant R01A1050875. NR 52 TC 15 Z9 15 U1 1 U2 57 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1388-0764 J9 J NANOPART RES JI J. Nanopart. Res. PD MAY PY 2013 VL 15 IS 5 AR 1651 DI 10.1007/s11051-013-1651-0 PG 14 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 139BC UT WOS:000318555400055 PM 24363607 ER PT J AU Catana, C Guimaraes, AR Rosen, BR AF Catana, Ciprian Guimaraes, Alexander R. Rosen, Bruce R. TI PET and MR Imaging: The Odd Couple or a Match Made in Heaven? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE multimodality imaging; PET/MR imaging; applications; oncology; neurology; cardiology ID LYMPH-NODE METASTASES; SUPERPARAMAGNETIC IRON-OXIDE; POSITRON-EMISSION-TOMOGRAPHY; WHOLE-BODY PET/MRI; ATTENUATION-CORRECTION; FDG-PET/CT; ALZHEIMERS-DISEASE; PROSTATE-CANCER; MAGNETIC NANOPARTICLES; PEDIATRIC ONCOLOGY AB PET and MR imaging are modalities routinely used for clinical and research applications. Integrated scanners capable of acquiring PET and MR imaging data in the same session, sequentially or simultaneously, have recently become available for human use. In this article, we describe some of the technical advances that allowed the development of human PET/MR scanners; briefly discuss methodologic challenges and opportunities provided by this novel technology; and present potential oncologic, cardiac, and neuropsychiatric applications. These examples range from studies that might immediately benefit from PET/MR to more advanced applications on which future development might have an even broader impact. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Catana, C (reprint author), AA Martinos Ctr, Bldg 149,13th St,Room 2-301, Charlestown, MA 02129 USA. EM ccatana@nmr.mgh.harvard.edu FU NCI NIH HHS [R01 CA137254] NR 75 TC 32 Z9 32 U1 0 U2 23 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 MAY 1 PY 2013 VL 54 IS 5 BP 815 EP 824 DI 10.2967/jnumed.112.112771 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 137CS UT WOS:000318413200046 PM 23492887 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Off-Label Use of Oncology Drugs: Too Much, Too Little, or Just Right? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 2 Z9 2 U1 1 U2 2 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 MAY PY 2013 VL 11 IS 5 BP 505 EP 506 PG 2 WC Oncology SC Oncology GA 141US UT WOS:000318752600001 PM 23667200 ER PT J AU Benson, AB Bekaii-Saab, T Chan, E Chen, YJ Choti, MA Cooper, HS Engstrom, PF Enzinger, PC Fakih, MG Fenton, MJ Fuchs, CS Grem, JL Hunt, S Kamel, A Leong, LA Lin, E May, KS Mulcahy, MF Murphy, K Rohren, E Ryan, DP Saltz, L Sharma, S Shibata, D Skibber, JM Small, W Sofocleous, CT Venook, AP Willett, CG Gregory, KM Freedman-Cass, DA AF Benson, Al B., III Bekaii-Saab, Tanios Chan, Emily Chen, Yi-Jen Choti, Michael A. Cooper, Harry S. Engstrom, Paul F. Enzinger, Peter C. Fakih, Marwan G. Fenton, Moon J. Fuchs, Charles S. Grem, Jean L. Hunt, Steven Kamel, Ahmed Leong, Lucille A. Lin, Edward May, Kilian Salerno Mulcahy, Mary F. Murphy, Kate Rohren, Eric Ryan, David P. Saltz, Leonard Sharma, Sunil Shibata, David Skibber, John M. Small, William, Jr. Sofocleous, Constantinos T. Venook, Alan P. Willett, Christopher G. Gregory, Kristina M. Freedman-Cass, Deborah A. TI Localized Colon Cancer, Version 3.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; STAGE-II; ADJUVANT CHEMOTHERAPY; MICROSATELLITE-INSTABILITY; MISMATCH REPAIR; LYNCH-SYNDROME; FOLINIC ACID; FLUOROURACIL; RECURRENCE; EFFICACY AB The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions regarding the treatment of localized disease for the 2013 update of the guidelines. C1 [Benson, Al B., III; Mulcahy, Mary F.; Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Bekaii-Saab, Tanios] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Chan, Emily] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Chen, Yi-Jen; Leong, Lucille A.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Choti, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Cooper, Harry S.; Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Enzinger, Peter C.; Fuchs, Charles S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Fakih, Marwan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Fenton, Moon J.] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Grem, Jean L.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Hunt, Steven] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Hunt, Steven] Washington Univ, Sch Med, St Louis, MO USA. [Kamel, Ahmed] Univ Alabama Birmingham Comprehens Canc Ctr, Birmingham, AL USA. [Lin, Edward] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [May, Kilian Salerno] Roswell Pk Canc Inst, Buffalo, NY USA. [Rohren, Eric; Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Saltz, Leonard; Sofocleous, Constantinos T.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Sharma, Sunil] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Shibata, David] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Venook, Alan P.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Willett, Christopher G.] Duke Canc Inst, Durham, NC USA. RP Benson, AB (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RI Bekaii-Saab, Tanios/E-2733-2011 NR 47 TC 44 Z9 45 U1 0 U2 7 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 MAY PY 2013 VL 11 IS 5 BP 519 EP 528 PG 10 WC Oncology SC Oncology GA 141US UT WOS:000318752600004 PM 23667203 ER PT J AU Ajani, JA Bentrem, DJ Besh, S D'Amico, TA Das, P Denlinger, C Fakih, MG Fuchs, CS Gerdes, H Glasgow, RE Hayman, JA Hofstetter, WL Ilson, DH Keswani, RN Kleinberg, LR Korn, WM Lockhart, AC Meredith, K Mulcahy, MF Orringer, MB Posey, JA Sasson, AR Scott, WJ Strong, VE Varghese, TK Warren, G Washington, MK Willett, C Wright, CD McMillian, NR Sundar, H AF Ajani, Jaffer A. Bentrem, David J. Besh, Stephen D'Amico, Thomas A. Das, Prajnan Denlinger, Crystal Fakih, Marwan G. Fuchs, Charles S. Gerdes, Hans Glasgow, Robert E. Hayman, James A. Hofstetter, Wayne L. Ilson, David H. Keswani, Rajesh N. Kleinberg, Lawrence R. Korn, W. Michael Lockhart, A. Craig Meredith, Kenneth Mulcahy, Mary F. Orringer, Mark B. Posey, James A. Sasson, Aaron R. Scott, Walter J. Strong, Vivian E. Varghese, Thomas K., Jr. Warren, Graham Washington, Mary Kay Willett, Christopher Wright, Cameron D. McMillian, Nicole R. Sundar, Hema TI Gastric Cancer, Version 2.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID LYMPH-NODE DISSECTION; PHASE-III TRIAL; GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA; RANDOMIZED CLINICAL-TRIAL; GENE AMPLIFICATION; D2 GASTRECTOMY; PERIOPERATIVE CHEMOTHERAPY; HER2 EXPRESSION; SURGICAL TRIAL; STAGE-II AB The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+. C1 [Ajani, Jaffer A.; Das, Prajnan; Hofstetter, Wayne L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bentrem, David J.; Keswani, Rajesh N.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Besh, Stephen] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [D'Amico, Thomas A.] Duke Canc Inst, Durham, NC USA. [Denlinger, Crystal; Scott, Walter J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Fakih, Marwan G.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Fuchs, Charles S.; Strong, Vivian E.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Gerdes, Hans; Ilson, David H.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Glasgow, Robert E.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Hayman, James A.; Kleinberg, Lawrence R.; Orringer, Mark B.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hayman, James A.; Kleinberg, Lawrence R.; Orringer, Mark B.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Korn, W. Michael] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Lockhart, A. Craig] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Lockhart, A. Craig] Washington Univ, Sch Med, St Louis, MO USA. [Meredith, Kenneth] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Posey, James A.] Univ Alabama Birmingham Comprehens Canc Ctr, Birmingham, AL USA. [Sasson, Aaron R.; Warren, Graham] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Varghese, Thomas K., Jr.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Warren, Graham] Roswell Pk Canc Inst, Buffalo, NY USA. [Washington, Mary Kay] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Wright, Cameron D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ajani, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 44 TC 147 Z9 169 U1 0 U2 12 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 MAY PY 2013 VL 11 IS 5 BP 531 EP 546 PG 16 WC Oncology SC Oncology GA 141US UT WOS:000318752600005 PM 23667204 ER PT J AU Ettinger, DS Riely, GJ Akerley, W Borghaei, H Chang, AC Cheney, RT Chirieac, LR D'Amico, TA Demmy, TL Govindan, R Grannis, FW Grant, SC Horn, L Jahan, TM Komaki, R Kong, FMS Kris, MG Krug, LM Lackner, RP Lennes, IT Loo, BW Martins, R Otterson, GA Patel, JD Pinder-Schenck, MC Pisters, KM Reckamp, K Rohren, E Shapiro, TA Swanson, SJ Tauer, K Wood, DE Yang, SC Gregory, K Hughes, M AF Ettinger, David S. Riely, Gregory J. Akerley, Wallace Borghaei, Hossein Chang, Andrew C. Cheney, Richard T. Chirieac, Lucian R. D'Amico, Thomas A. Demmy, Todd L. Govindan, Ramaswamy Grannis, Frederic W., Jr. Grant, Stefan C. Horn, Leora Jahan, Thierry M. Komaki, Ritsuko (Spring) Kong, Feng-Ming Kris, Mark G. Krug, Lee M. Lackner, Rudy P. Lennes, Inga T. Loo, Billy W., Jr. Martins, Renato Otterson, Gregory A. Patel, Jyoti D. Pinder-Schenck, Mary C. Pisters, Katherine M. Reckamp, Karen Rohren, Eric Shapiro, Theresa A. Swanson, Scott J. Tauer, Kurt Wood, Douglas E. Yang, Stephen C. Gregory, Kristina Hughes, Miranda TI Thymomas and Thymic Carcinomas Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ADJUVANT RADIATION-THERAPY; ENDOCRINE NEOPLASIA TYPE-1; PRIMARY MEDIASTINAL TUMORS; STAGE IVA THYMOMA; OF-THE-ART; EPITHELIAL TUMORS; PHASE-II; INVASIVE THYMOMA; POSTOPERATIVE RADIOTHERAPY; SURGICAL RESECTION AB Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors. C1 [Ettinger, David S.; Yang, Stephen C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkin, Baltimore, MD USA. [Riely, Gregory J.; Kris, Mark G.; Krug, Lee M.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA USA. [Chang, Andrew C.; (Spring) Kong, Feng-Ming] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cheney, Richard T.; Demmy, Todd L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Chirieac, Lucian R.; Swanson, Scott J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [D'Amico, Thomas A.] Duke Canc Inst, Durham, NC USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Govindan, Ramaswamy] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Grannis, Frederic W., Jr.; Reckamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Grant, Stefan C.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jahan, Thierry M.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Komaki, Ritsuko; Pisters, Katherine M.; Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Lackner, Rudy P.] UNMC Eppley Canc Ctr, Nebraska Med Ctr, Omaha, NE USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Martins, Renato; Wood, Douglas E.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Martins, Renato; Wood, Douglas E.] Seattle Canc Care Alliance, Seattle, WA USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Otterson, Gregory A.] Solove Res Inst, Columbus, OH USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Pinder-Schenck, Mary C.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Wood, Douglas E.] Univ Tennessee, Inst Canc, Knoxville, TN 37996 USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkin, Baltimore, MD USA. NR 131 TC 10 Z9 11 U1 1 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 MAY PY 2013 VL 11 IS 5 BP 562 EP 576 PG 15 WC Oncology SC Oncology GA 141US UT WOS:000318752600007 PM 23667206 ER PT J AU Clark, PE Spiess, PE Agarwal, N Biagioli, MC Eisenberger, MA Greenberg, RE Herr, HW Inman, BA Kuban, DA Kuzel, TM Lele, SM Michalski, J Pagliaro, L Pal, SK Patterson, A Plimack, ER Pohar, KS Porter, MP Richie, JP Sexton, WJ Shipley, WU Small, EJ Trump, DL Wile, G Wilson, TG Dwyer, M Ho, M AF Clark, Peter E. Spiess, Philippe E. Agarwal, Neeraj Biagioli, Matthew C. Eisenberger, Mario A. Greenberg, Richard E. Herr, Harry W. Inman, Brant A. Kuban, Deborah A. Kuzel, Timothy M. Lele, Subodh M. Michalski, Jeff Pagliaro, Lance Pal, Sumanta K. Patterson, Anthony Plimack, Elizabeth R. Pohar, Kamal S. Porter, Michael P. Richie, Jerome P. Sexton, Wade J. Shipley, William U. Small, Eric J. Trump, Donald L. Wile, Geoffrey Wilson, Timothy G. Dwyer, Mary Ho, Maria TI Penile Cancer Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID SQUAMOUS-CELL CARCINOMA; SENTINEL NODE-BIOPSY; IMIQUIMOD 5-PERCENT CREAM; ENDOSCOPIC INGUINAL LYMPHADENECTOMY; CURRENT TNM CLASSIFICATION; FINE-NEEDLE-ASPIRATION; ORGAN-SPARING SURGERY; PROGNOSTIC-FACTORS; IN-SITU; INTERSTITIAL BRACHYTHERAPY AB Squamous cell carcinoma of the penis represents approximately 0.5% of all cancers among men in the United States and other developed countries. Although rare, it is associated with significant disfigurement, and only half of the patients survive beyond 5 years. Proper evaluation of both the primary lesion and lymph nodes is critical, because nodal involvement is the most important factor of survival. The NCCN Clinical Practice Guidelines in Oncology for Penile Cancer provide recommendations on the diagnosis and management of this devastating disease based on evidence and expert consensus. C1 [Clark, Peter E.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Agarwal, Neeraj; Wile, Geoffrey] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Spiess, Philippe E.; Biagioli, Matthew C.; Sexton, Wade J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Eisenberger, Mario A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Greenberg, Richard E.; Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Herr, Harry W.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Inman, Brant A.] Duke Canc Inst, Durham, NC USA. [Kuban, Deborah A.; Pagliaro, Lance] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Kuzel, Timothy M.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Lele, Subodh M.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Michalski, Jeff] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Michalski, Jeff] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Pal, Sumanta K.; Wilson, Timothy G.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Patterson, Anthony] St Jude Childrens Res Hosp, Memphis, TN USA. [Patterson, Anthony] Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Pohar, Kamal S.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Pohar, Kamal S.] Solove Res Inst, Columbus, OH USA. [Porter, Michael P.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Richie, Jerome P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Shipley, William U.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Small, Eric J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Trump, Donald L.] Roswell Pk Canc Inst, Buffalo, NY USA. RP Clark, PE (reprint author), Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RI Clark, Peter/E-1423-2011 OI Clark, Peter/0000-0002-8006-7015 FU NCI NIH HHS [P30 CA006973] NR 106 TC 18 Z9 19 U1 0 U2 2 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 MAY PY 2013 VL 11 IS 5 BP 594 EP 615 PG 22 WC Oncology SC Oncology GA 141US UT WOS:000318752600010 PM 23667209 ER PT J AU Patel, VI Kang, J Mukhopadhyay, S Conrad, MF Brewster, DC Kwolek, CJ Cambria, RP LaMuraglia, GM AF Patel, Virendra I. Kang, Jeanwan Mukhopadhyay, Shankha Conrad, Mark F. Brewster, David C. Kwolek, Christopher J. Cambria, Richard P. LaMuraglia, Glenn M. TI Severe Contralateral Carotid Stenosis or Occlusion Does Not Impact Risk of Ipsilateral Stroke Following CEA SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Patel, Virendra I.; Kang, Jeanwan; Mukhopadhyay, Shankha; Conrad, Mark F.; Brewster, David C.; Kwolek, Christopher J.; Cambria, Richard P.; LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 6S EP 7S PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300008 ER PT J AU Raux, M Patel, VI Cochennec, F Mukhopadhyay, S Desgranges, P Cambria, RP Becquemin, JP LaMuraglia, GM AF Raux, Maxime Patel, Virendra I. Cochennec, Frederic Mukhopadhyay, Shankha Desgranges, Pascal Cambria, Richard P. Becquemin, Jean-Pierre LaMuraglia, Glenn M. TI A Propensity-Matched Comparison of Fenestrated EVAR and Open Surgical Repair of Complex Abdominal Aortic Aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Raux, Maxime; Cochennec, Frederic; Desgranges, Pascal; Becquemin, Jean-Pierre] Hop Henri Mondor, F-94010 Creteil, France. [Patel, Virendra I.; Mukhopadhyay, Shankha; Cambria, Richard P.; LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 20S EP 21S PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300036 ER PT J AU Lombardi, JV Cambria, RP Nienaber, C Chiesa, R Teebken, O Lee, A Mossop, P Haulon, S Zhou, Q Jia, FY AF Lombardi, Joseph V. Cambria, Richard P. Nienaber, Christoph Chiesa, Roberto Teebken, Omkee Lee, Anthony Mossop, Peter Haulon, Stephan Zhou, Qing Jia, Feiyi TI Aortic Remodeling After Endovascular Treatment of Complicated Type B Aortic Dissection Using a Composite Device Design: A Report from the STABLE Trial SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Lombardi, Joseph V.] Cooper Univ Hosp, Camden, NJ USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nienaber, Christoph] Univ Hosp Rostock, Rostock, Germany. [Chiesa, Roberto] Hosp San Raffaele, I-20132 Milan, Italy. [Teebken, Omkee] Hannover Med Sch, Hannover, Germany. [Lee, Anthony] Christine E Lynn Heart & Vasc Inst, Boca Raton, FL USA. [Mossop, Peter] St Vincents Hosptal, Melbourne, Vic, Australia. [Haulon, Stephan] Chru Lille, Hosp Cardiol, Lille, France. [Zhou, Qing; Jia, Feiyi] Med Institutel, W Lafayette, IN USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 21S EP 22S PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300038 ER PT J AU Morrison, TM Meyer, CA Fillinger, MF Fairman, RM Glickman, MH Cambria, RP Farber, MA Naslund, TC Fail, PS Elmore, JR White, RA Dall'Olmo, CA Williams, DM AF Morrison, Tina M. Meyer, Clark A. Fillinger, Mark F. Fairman, Ron M. Glickman, Marc H. Cambria, Richard P. Farber, Mark A. Naslund, Thomas C. Fail, Peter S. Elmore, James R. White, Rodney A. Dall'Olmo, Carlo A. Williams, David M. TI Eligiblity for Endovascular Repair of Short Neck Abdominal Aortic Aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Morrison, Tina M.; Meyer, Clark A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Fillinger, Mark F.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Fairman, Ron M.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Glickman, Marc H.] Sentara Norfolk Gen Hosp, Norfolk, VA USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farber, Mark A.] Univ N Carolina, Med Ctr, Chapel Hill, NC USA. [Naslund, Thomas C.] Vanderbilt Univ Sch Med, Nashville, TN USA. [Fail, Peter S.] Cardiovasc Inst South, Houma, LA USA. [Elmore, James R.] Geisinger Med Ctr, Danville, PA 17822 USA. [White, Rodney A.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Dall'Olmo, Carlo A.] Michigan Vasc Ctr, Flint, MI USA. [Williams, David M.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 24S EP 24S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300042 ER PT J AU Conrad, MF Mukhopadhyay, S Michalczyk, MJ Opalacz, A LaMuraglia, GM Cambria, RP AF Conrad, Mark F. Mukhopadhyay, Shankha Michalczyk, Michael J. Opalacz, Arissa LaMuraglia, Glenn M. Cambria, Richard P. TI Natural History of Asymptomatic Severe Carotid Artery Stenosis SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Conrad, Mark F.; Mukhopadhyay, Shankha; Michalczyk, Michael J.; Opalacz, Arissa; LaMuraglia, Glenn M.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 27S EP 27S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300048 ER PT J AU Simons, JP Baril, D Goodney, PP Hevelone, ND Bertges, DJ Patel, VI Robinson, WP Cronenwett, JL Messina, LM Schanzer, A AF Simons, Jessica P. Baril, Donald Goodney, Philip P. Hevelone, Nathanael D. Bertges, Daniel J. Patel, Virendra I. Robinson, William P. Cronenwett, Jack L. Messina, Louis M. Schanzer, Andres TI The Effect of Postoperative Myocardial Ischemia on Long-Term Survival After Vascular Surgery SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Simons, Jessica P.; Robinson, William P.; Messina, Louis M.; Schanzer, Andres] Univ Massachusetts, Sch Med, Div Vasc & Endovasc Surg, Worcester, MA USA. [Goodney, Philip P.; Cronenwett, Jack L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Hevelone, Nathanael D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bertges, Daniel J.] Univ Vermont, Coll Med, Burlington, VT USA. [Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 29S EP 29S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300052 ER PT J AU Lo, RC Fokkema, M Curran, T Darling, J Wyers, M Hamdan, AD Chaikof, EL Schermerhorn, ML AF Lo, Ruby C. Fokkema, Margriet Curran, Thomas Darling, Jeremy Wyers, Mark Hamdan, Allen D. Chaikof, Elliot L. Schermerhorn, Marc L. TI Predictors of Access-Site Related Complications After Lower Extremity Percutaneous Revascularization SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Lo, Ruby C.; Fokkema, Margriet; Curran, Thomas; Darling, Jeremy; Wyers, Mark; Hamdan, Allen D.; Chaikof, Elliot L.; Schermerhorn, Marc L.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 51S EP 51S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300096 ER PT J AU Zhang, J Curran, T Fokkema, M Lo, RC Wyers, M Hamdan, A Chaikof, E Schermerhorn, ML AF Zhang, Jennifer Curran, Thomas Fokkema, Margriet Lo, Ruby C. Wyers, Mark Hamdan, Alan Chaikof, Elliot Schermerhorn, Marc L. TI Predictors of 30-Day Readmission and Analysis of Complications After Lower Extremity Bypass Using NSQIP SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Zhang, Jennifer; Curran, Thomas; Fokkema, Margriet; Lo, Ruby C.; Wyers, Mark; Hamdan, Alan; Chaikof, Elliot; Schermerhorn, Marc L.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 60S EP 60S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300113 ER PT J AU Lee, A Peterson, C Moll, H Csizmadia, E Rogers, A Neidich, A Chien, V da Silva, C Ferran, C AF Lee, Andy Peterson, Clayton Moll, Herwig Csizmadia, Eva Rogers, Ashley Neidich, Alon Chien, Victor da Silva, Cleide Ferran, Christiane TI Loss of Function Studies Highlight the Vasculoprotective Effect of A20 in Transplant Arteriosclerosis (TA) SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Lee, Andy; Peterson, Clayton; Moll, Herwig; Csizmadia, Eva; Rogers, Ashley; Chien, Victor; da Silva, Cleide; Ferran, Christiane] BIDMC, Boston, MA USA. [Neidich, Alon] Tufts Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 77S EP 78S PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300148 ER PT J AU Chien, V Kaczmarek, E Daniel, S Essayagh, S Choi, L Choi, J Lee, A da Silva, C Ferran, C AF Chien, Victor Kaczmarek, Elzbieta Daniel, Soizic Essayagh, Sanah Choi, Lynn Choi, Jean Lee, Andy da Silva, Cleide Ferran, Christiane TI A20 Increases eNOS Expression and Activity to Sustain Endothelial Cell Function Under Inflammatory Insults SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Chien, Victor; Kaczmarek, Elzbieta; Daniel, Soizic; Essayagh, Sanah; Choi, Lynn; Choi, Jean; Lee, Andy; da Silva, Cleide; Ferran, Christiane] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 79S EP 79S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300151 ER PT J AU Patel, VI Ergul, E Conrad, MF Gravereaux, E Schermerhorn, ML Schanzer, A Goodney, PP Cambria, RP AF Patel, Virendra I. Ergul, Emel Conrad, Mark F. Gravereaux, Edwin Schermerhorn, Marc L. Schanzer, Andres Goodney, Philip P. Cambria, Richard P. TI Aneurysm Sac Enlargement Independently Predicts Late Mortality in Patients Treated With EVAR SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Patel, Virendra I.; Ergul, Emel; Conrad, Mark F.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gravereaux, Edwin; Schermerhorn, Marc L.; Schanzer, Andres; Goodney, Philip P.] Vasc Study Grp New England, Lebanon, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 87S EP 88S PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300169 ER PT J AU Fokkema, M Goodney, PP Nedeau, AE Baribeau, YR Patel, VI Moll, FL de Borst, GJ Schermerhorn, ML AF Fokkema, Margriet Goodney, Philip P. Nedeau, April E. Baribeau, Yvonne R. Patel, Virendra I. Moll, Frans L. de Borst, Gert Jan Schermerhorn, Marc L. TI Symptom Status and Degree of Ipsilateral Stenosis Determine Whether Contralateral Stenosis Increases the Risk for Carotid Revascularization SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Fokkema, Margriet; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Goodney, Philip P.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Nedeau, April E.] Cent Maine Med Ctr, Lewiston, ME USA. [Baribeau, Yvonne R.] New England Heart Inst, Manchester, NH USA. [Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moll, Frans L.; de Borst, Gert Jan] Univ Med Ctr Utrecht, Utrecht, Netherlands. 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 93S EP 93S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300180 ER PT J AU Smith, AD Schaumeier, MJ Hawkins, AT Hevelone, ND Nguyen, LL AF Smith, Ann D. Schaumeier, Maria J. Hawkins, Alexander T. Hevelone, Nathanael D. Nguyen, Louis L. TI Predictors of Major Amputation With Patent Bypass Grafts SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Smith, Ann D.; Nguyen, Louis L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schaumeier, Maria J.; Hevelone, Nathanael D.] Ctr Surg & Publ Hlth, Boston, MA USA. [Hawkins, Alexander T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 98S EP 99S PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300192 ER PT J AU Mosse, YP Lim, MS Voss, SD Wilner, K Ruffner, K Laliberte, J Rolland, D Balis, FM Maris, JM Weigel, BJ Ingle, AM Ahern, C Adamson, PC Blaney, SM AF Mosse, Yael P. Lim, Megan S. Voss, Stephan D. Wilner, Keith Ruffner, Katherine Laliberte, Julie Rolland, Delphine Balis, Frank M. Maris, John M. Weigel, Brenda J. Ingle, Ashish M. Ahern, Charlotte Adamson, Peter C. Blaney, Susan M. TI Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study SO LANCET ONCOLOGY LA English DT Article ID ALK GENE REARRANGEMENT; LUNG-CANCER; ACTIVATING MUTATIONS; ONCOGENIC MUTATIONS; KINASE; NEUROBLASTOMA; IDENTIFICATION; CHEMOTHERAPY; FUSION; ADOLESCENTS AB Background Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. Methods In this open-label, phase 1 dose-escalation trial, patients older than 12 months and younger than 22 years with measurable or evaluable solid or CNS tumours, or anaplastic large-cell lymphoma, refractory to therapy and for whom there was no known curative treatment were eligible. Crizotinib was given twice daily without interruption. Six dose levels (100, 130, 165, 215, 280, 365 mg/m(2) per dose) were assessed in the dose-finding phase of the study (part A1), which is now completed. The primary endpoint was to estimate the maximum tolerated dose, to define the toxic effects of crizotinib, and to characterise the pharmacokinetics of crizotinib in children with refractory cancer. Additionally, patients with confirmed ALK translocations, mutations, or amplification (part A2 of the study) or neuroblastoma (part A3) could enrol at one dose level lower than was currently given in part A1. We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma. All patients who received at least one dose of crizotinib were evaluable for response; patients completing at least one cycle of therapy or experiencing dose limiting toxicity before that were considered fully evaluable for toxicity. This study is registered with ClinicalTrials. gov, NCT00939770. Findings 79 patients were enrolled in the study from Oct 2, 2009, to May 31, 2012. The median age was 10.1 years (range 1.1-21.4); 43 patients were included in the dose escalation phase (A1), 25 patients in part A2, and 11 patients in part A3. Crizotinib was well tolerated with a recommended phase 2 dose of 280 mg/m(2) twice daily. Grade 4 adverse events in cycle 1 were neutropenia (two) and liver enzyme elevation (one). Grade 3 adverse events that occurred in more than one patient in cycle 1 were lymphopenia (two), and neutropenia (eight). The mean steady state peak concentration of crizotinib was 630 ng/mL and the time to reach this peak was 4 h (range 1-6). Objective tumour responses were documented in 14 of 79 patients (nine complete responses, five partial responses); and the antitumour activity was enriched in patients with known activating ALK aberrations (eight of nine with anaplastic large-cell lymphoma, one of 11 with neuroblastoma, three of seven with inflammatory myofibroblastic tumour, and one of two with NSCLC). Interpretation The findings suggest that a targeted inhibitor of ALK has antitumour activity in childhood malignancies harbouring ALK translocations, particularly anaplastic large-cell lymphoma and inflammatory myofibroblastic tumours, and that further investigation in the subset of neuroblastoma harbouring known ALK oncogenic mutations is warranted. C1 [Mosse, Yael P.; Balis, Frank M.; Maris, John M.; Adamson, Peter C.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Mosse, Yael P.; Balis, Frank M.; Maris, John M.; Adamson, Peter C.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Mosse, Yael P.; Balis, Frank M.; Maris, John M.; Adamson, Peter C.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lim, Megan S.; Laliberte, Julie; Rolland, Delphine] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Voss, Stephan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp,Dept Radiol, Boston, MA 02115 USA. [Wilner, Keith; Ruffner, Katherine] Pfizer Oncol, La Jolla, CA USA. [Weigel, Brenda J.] Univ Minnesota, Ctr Canc, Div Pediat Oncol, Minneapolis, MN USA. [Ingle, Ashish M.] Childrens Oncol Grp, Operat Ctr, Monrovia, CA USA. [Ahern, Charlotte; Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. RP Mosse, YP (reprint author), Childrens Hosp Philadelphia, 3501 Civ Ctr Blvd,CTRB 3056, Philadelphia, PA 19104 USA. EM mosse@chop.edu FU Pfizer; National Cancer Institute; COG phase 1 and Pilot Consortium [U01] FX Pfizer and National Cancer Institute grant to the Children's Oncology Group.; Funding for this trial was provided to the COG phase 1 and Pilot Consortium through a U01 mechanism and by Pfizer. We thank Biljana Georgievska, COG phase 1 Operations Director and the staff in the COG Operations office. We thank Per Kogner (Karolinska Institute, Stockholm, Sweden) for his patient referral NR 31 TC 174 Z9 180 U1 6 U2 22 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 MAY PY 2013 VL 14 IS 6 BP 472 EP 480 DI 10.1016/S1470-2045(13)70095-0 PG 9 WC Oncology SC Oncology GA 140UN UT WOS:000318681500036 PM 23598171 ER PT J AU Motzer, RJ Escudier, B Tomczak, P Hutson, TE Michaelson, MD Negrier, S Oudard, S Gore, ME Tarazi, J Hariharan, S Chen, C Rosbrook, B Kim, S Rini, BI AF Motzer, Robert J. Escudier, Bernard Tomczak, Piotr Hutson, Thomas E. Michaelson, M. Dror Negrier, Sylvie Oudard, Stephane Gore, Martin E. Tarazi, Jamal Hariharan, Subramanian Chen, Connie Rosbrook, Brad Kim, Sinil Rini, Brian I. TI Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID PROGRESSION-FREE SURVIVAL; PROGNOSTIC-FACTORS; EFFICACY; EVEROLIMUS; BIOMARKER AB Background In a phase 3 trial comparing the efficacy and safety of axitinib versus sorafenib as second-line treatment for metastatic renal cell carcinoma, patients given axitinib had a longer progression-free survival (PFS). Here, we report overall survival and updated efficacy, quality of life, and safety results. Methods Eligible patients had clear cell metastatic renal cell carcinoma, progressive disease after one approved systemic treatment, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.723 patients were stratified by ECOG PS and previous treatment and randomly allocated (1:1) to receive axitinib (5 mg twice daily; n=361) or sorafenib (400 mg twice daily; n=362). The primary endpoint was PFS assessed by a masked, independent radiology review committee. We assessed patient-reported outcomes using validated questionnaires. Baseline characteristics and development of hypertension on treatment were studied as prognostic factors. Efficacy was assessed in the intention-to-treat population, and safety was assessed in patients who received at least one dose of the study drug. This ongoing trial is registered on ClinicalTrials.gov, number NCT00678392. Findings Median overall survival was 20.1 months (95% CI 16.7-23.4) with axitinib and 19.2 months (17.5-22.3) with sorafenib (hazard ratio [HR] 0.969, 95% CI 0.800-1.174; one-sided p=0.3744). Median investigator-assessed PFS was 8.3 months (95% CI 6.7-9.2) with axitinib and 5.7 months (4.7-6.5) with sorafenib (HR 0.656, 95% CI 0.552-0.779; one-sided p<0.0001). Patient-reported outcomes scores were similar in the treatment groups at baseline, were maintained during treatment, but decreased at end-of-treatment. Common grade 3 or higher treatment-related adverse events were hypertension (60 [17%]), diarrhoea (40 [11%]), and fatigue (37 [10%]) in 359 axitinib-treated patients and hand-foot syndrome (61 [17%]), hypertension (43 [12%]), and diarrhoea (27 [8%]) in 355 sorafenib-treated patients. In a post-hoc 12-week landmark analysis, median overall survival was longer in patients with a diastolic blood pressure of 90 mm Hg or greater than in those with a diastolic blood pressure of less than 90 mm Hg: 20.7 months (95% CI 18.4-24.6) versus 12.9 months (10.1-20.4) in the axitinib group (p=0.0116), and 20.2 months (17.1-32.0) versus 14.8 months (12.0-17.7) in the sorafenib group (one-sided p=0.0020). Interpretation Although overall survival, a secondary endpoint for the study, did not differ between the two groups, investigator-assessed PFS remained longer in the axitinib group compared with the sorafenib group. These results establish axitinib as a second-line treatment option for patients with metastatic renal cell carcinoma. C1 [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Escudier, Bernard] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Tomczak, Piotr] Uniwersytet Med, Klin Onkol, Poznan, Poland. [Hutson, Thomas E.] Baylor Sammons & Texas Oncol Phys Assoc, Sammons Canc Ctr, Dallas, TX USA. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Negrier, Sylvie] Ctr Leon Berard, Serv Oncol Med, F-69373 Lyon, France. [Oudard, Stephane] Univ Paris 05, Georges Pompidou European Hosp, Paris, France. [Gore, Martin E.] Royal Marsden Hosp, London SW3 6JJ, England. [Tarazi, Jamal; Rosbrook, Brad; Kim, Sinil] Pfizer Oncol, San Diego, CA USA. [Hariharan, Subramanian] Pfizer Inc, New York, NY USA. [Chen, Connie] Pfizer Inc, Global Outcomes Res, New York, NY USA. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM motzerr@mskcc.org OI Michaelson, Dror/0000-0001-9249-6338 FU Pfizer Inc.; Pfizer; Bayer; GlaxoSmithKline; Novartis; Genentech; Eisai; Eisai, Bayer; Abbott; Sanofi-Aventis FX Pfizer Inc.; RJM has served as a consultant or adviser for Pfizer and has received research funding from Pfizer, Novartis, and GlaxoSmithKline. BE has served as a consultant or adviser for Bayer, Pfizer, and Novartis, and has received honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, and Aveo. TEH has served as a consultant or adviser for and received honoraria and research funding from Pfizer, Bayer, GlaxoSmithKline, and Novartis. MDM has served as a consultant or adviser for Pfizer, Novartis, Aveo, Genentech, and Abbott and has received research funding from GlaxoSmithKline, Genentech, Pfizer, Novartis, Eisai, Bayer, and Abbott. SN has served as a consultant or adviser for Novartis and Pfizer; has received honoraria from Novartis, Pfizer, GlaxoSmithKline, and Roche; and has received research funding from Novartis, Pfizer, and GlaxoSmithKline. SO has served as a consultant or adviser for Roche, Sanofi-Aventis, Novartis, and Bayer; has received honoraria from Pfizer, Bayer, Novartis, Keocyt, Amgen, Roche, and Sanofi-Aventis; and has received research funding from Sanofi-Aventis and Bayer. MEG has served as a consultant or adviser for and received honoraria from Pfizer and Bayer. JT, SH, CC, BR, and SK are employees of and own stock in Pfizer. BIR has served as a consultant or adviser for and received research funding from Pfizer. PT declares that he has no conflicts of interest.; See the appendix for a full list of participating countries and principal investigators. This study was sponsored by Pfizer Inc. Medical writing support, also funded by Pfizer Inc, was provided by Joanna Bloom, of UBC Scientific Solutions (Southport, CT, USA). NR 10 TC 234 Z9 239 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 MAY PY 2013 VL 14 IS 6 BP 552 EP 562 DI 10.1016/S1470-2045(13)70093-7 PG 11 WC Oncology SC Oncology GA 140UN UT WOS:000318681500044 PM 23598172 ER PT J AU Carbone, K AF Carbone, Kathryn TI Untitled SO MCN-THE AMERICAN JOURNAL OF MATERNAL-CHILD NURSING LA English DT Editorial Material C1 James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Carbone, K (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY USA. EM Kathryn.Carbone@va.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-929X J9 MCN-AM J MATERN-CHIL JI MCN-Am. J. Matern.-Child Nurs. PD MAY-JUN PY 2013 VL 38 IS 3 BP 135 EP 135 PG 1 WC Nursing SC Nursing GA 140WA UT WOS:000318685800003 ER PT J AU Chung, HJ Castro, CM Im, H Lee, H Weissleder, R AF Chung, Hyun Jung Castro, Cesar M. Im, Hyungsoon Lee, Hakho Weissleder, Ralph TI A magneto-DNA nanoparticle system for rapid detection and phenotyping of bacteria SO NATURE NANOTECHNOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; CARE-ASSOCIATED INFECTIONS; PCR ASSAY; IDENTIFICATION; DIAGNOSIS; CELLS AB So far, although various diagnostic approaches for pathogen detection have been proposed, most are too expensive, lengthy or limited in specificity for clinical use. Nanoparticle systems with unique material properties, however, circumvent these problems and offer improved accuracy over current methods. Here, we present novel magneto-DNA probes capable of rapid and specific profiling of pathogens directly in clinical samples. A nanoparticle hybridization assay, involving ubiquitous and specific probes that target bacterial 16S rRNAs, was designed to detect amplified target DNAs using a miniaturized NMR device. Ultimately, the magneto-DNA platform will allow both universal and specific detection of various clinically relevant bacterial species, with sensitivity down to single bacteria. Furthermore, the assay is robust and rapid, simultaneously diagnosing a panel of 13 bacterial species in clinical specimens within 2 h. The generic platform described could be used to rapidly identify and phenotype pathogens for a variety of applications. C1 [Chung, Hyun Jung; Castro, Cesar M.; Im, Hyungsoon; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Castro, Cesar M.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu RI Im, Hyungsoon/A-3178-2009; Chung, Hyun Jung/J-3205-2014 OI Im, Hyungsoon/0000-0002-0626-1346; FU National Institute of Health [R01EB004626, R01EB010011, HHSN268201000044C, R01HL113156] FX The authors thank Y. Fisher-Jeffes for reviewing the manuscript, N. Sergeyev for synthesis of MNPs, S. Chen and M. Mckee for help with electron microscopy, C. Min for help with the mu NMR device, and J. Chung, K. S. Yang, J. Carlson, H. Shao and A. V. Ullal for assistance and many helpful discussions. The work was funded in part by National Institute of Health (grants R01EB004626, R01EB010011, HHSN268201000044C and R01HL113156). NR 33 TC 118 Z9 119 U1 15 U2 151 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD MAY PY 2013 VL 8 IS 5 BP 369 EP 375 DI 10.1038/NNANO.2013.70 PG 7 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 140VQ UT WOS:000318684800020 PM 23644570 ER PT J AU Walensky, LD AF Walensky, Loren D. TI Direct BAKtivation SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID BH3 DOMAINS; MITOCHONDRIAL APOPTOSIS; PROAPOPTOTIC BAX; ACTIVATION; BCL-2; MEMBRANE; PERMEABILIZATION; OLIGOMERIZATION; INHIBITOR; BINDING C1 [Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Dept Pediat Oncol, Boston, MA 02115 USA. [Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Linde Program Canc Chem Bio, Boston, MA 02115 USA. RP Walensky, LD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM loren_walensky@dfci.harvard.edu FU NCI NIH HHS [R01 CA050239]; NIGMS NIH HHS [R01 GM090299] NR 22 TC 3 Z9 3 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2013 VL 20 IS 5 BP 536 EP 538 DI 10.1038/nsmb.2579 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 139WZ UT WOS:000318617000003 PM 23649360 ER PT J AU Awad, AJ Walcott, BP Stapleton, CJ Yanamadala, V Nahed, BV Coumans, JV AF Awad, Ahmed J. Walcott, Brian P. Stapleton, Christopher J. Yanamadala, Vijay Nahed, Brian V. Coumans, Jean-Valery TI Dabigatran, intracranial hemorrhage, and the neurosurgeon SO NEUROSURGICAL FOCUS LA English DT Article DE stroke; fatal outcome; tracheostomy; decompressive craniectomy; warfarin; Pradaxa; dabigatran etexilate ID DIRECT THROMBIN INHIBITOR; PROTHROMBIN COMPLEX CONCENTRATE; RE-LY TRIAL; ATRIAL-FIBRILLATION; COAGULATION ASSAYS; INTRACEREBRAL HEMORRHAGE; ANTICOAGULANT ACTIVITY; WARFARIN; ETEXILATE; PHARMACOKINETICS AB Dabigatran etexilate (Pradaxa) is a novel oral anticoagulant that has gained FDA approval for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In randomized trials, the incidence of hemorrhagic events has been demonstrated to be lower in patients treated with dabigatran compared with the traditional anticoagulant warfarin. However, dabigatran does not have reliable laboratory tests to measure levels of anticoagulation and there is no pharmacological antidote. These drawbacks are challenging in the setting of intracerebral hemorrhage. In this article, the authors provide background information on dabigatran, review the existing anecdotal experiences with treating intracerebral hemorrhage related to dabigatran therapy, present a case study of intracranial hemorrhage in a patient being treated with dabigatran, and suggest clinical management strategies. The development of reversal agents is urgently needed given the growing number of patients treated with this medication. C1 [Awad, Ahmed J.] An Najah Natl Univ, Fac Med & Hlth Sci, Nablus, West Bank, Israel. [Walcott, Brian P.; Stapleton, Christopher J.; Yanamadala, Vijay; Nahed, Brian V.; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Stapleton, Christopher J.; Yanamadala, Vijay; Nahed, Brian V.; Coumans, Jean-Valery] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 39 TC 8 Z9 8 U1 2 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD MAY PY 2013 VL 34 IS 5 AR E7 DI 10.3171/2013.2.FOCUS1323 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 138DR UT WOS:000318489300008 PM 23634926 ER PT J AU Osaki, TH Jakobiec, FA Mendoza, PR Lee, Y Fay, AM AF Osaki, Tammy H. Jakobiec, Frederick A. Mendoza, Pia R. Lee, Yongjae Fay, Aaron M. TI Immunohistochemical Investigations of Orbital Infantile Hemangiomas and Adult Encapsulated Cavernous Venous Lesions (Malformation Versus Hemangioma) SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID GLUT-1 GLUCOSE-TRANSPORTER; PORT-WINE STAIN; VASCULAR MALFORMATIONS; CAPILLARY HEMANGIOMA; LYMPHATIC MALFORMATIONS; JUVENILE HEMANGIOMAS; TUMORS; CLASSIFICATION; ENDOTHELIUM; DIAGNOSIS AB Purpose: Immunohistochemical studies have begun to advance knowledge regarding the pathogenesis of vascular anomalies in many anatomical regions. However, the immunohistochemical features of most orbital tumors have been overlooked. Therefore, a comparative immunohistochemical study of a series of the 2 most common orbital vascular lesions infantile hemangioma (IH) and encapsulated cavernous venous lesion (ECVL), the latter also termed cavernous hemangioma or venous malformation-was undertaken. Methods: Twenty surgically excised orbital tumors diagnosed clinically and histopathologically as IHs (10 cases) or "cavernous hemangioma" (10 cases) were evaluated pathologically and immunohistochemically using hematoxylin and eosin, Alcian blue, Masson trichrome, GLUT-1, CD31, CD34, D2-40, smooth muscle actin (SMA), desmin, and Ki-67 probes. Results: All cases reacted strongly with the traditional blood vessel endothelial markers CD31 and CD34 and were negative for D2-40, a selective marker for lymphatic endothelium. All IH were positive for GLUT-1, and all ECVL were negative for GLUT-1. In IH, SMA (but not desmin) stained a monolayer of pericytes and in ECVL multilaminar smooth muscle vascular mural cells and intravascular (interstitial) stromal cells. Nuclear Ki-67 immunostaining was strongly positive in IH (average of 16.3%) and close to zero in ECVL. Conclusions: Immunophenotypic results for ECVL and IH demonstrated no overlapping staining patterns. Infantile hemangioma had the classical architecture of capillaries. Because of the constant presence of mural smooth muscle, it was concluded that ECVL is an accurate and descriptive term. However, desmin negativity in ECVL indicates myofibroblastic differentiation rather than full-fledged smooth muscle differentiation. Infantile hemangioma may display ectatic channels as the lesion ages but does not acquire multilaminar smooth muscle walls. Its pericytes lack cytoplasmic filaments and desmin reactivity but are SMA-positive because of the presence of poorly polymerized actin in the cytosol. In IH, Ki-67 positivity was observed in the endothelial cells of the solid and more ectatic regions. In contrast, the virtual absence of Ki-67 positivity in ECVL lends further support for the interpretation that it is more closely related to a malformation than a benign neoplasm. C1 [Osaki, Tammy H.; Jakobiec, Frederick A.; Mendoza, Pia R.; Fay, Aaron M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Osaki, Tammy H.] Univ Fed Sao Paulo, Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. [Jakobiec, Frederick A.; Mendoza, Pia R.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Lee, Yongjae] Univ Ulsan, Sch Med, Dept Ophthalmol, Ulsan 680749, South Korea. [Fay, Aaron M.] Massachusetts Eye & Ear Infirm, Dept Ophthalm Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 328,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu RI Osaki, Tammy /G-1539-2016; Menezes, Isabel/D-9281-2012 NR 70 TC 8 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2013 VL 29 IS 3 BP 183 EP 195 DI 10.1097/IOP.0b013e31828b0f1f PG 13 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 142HM UT WOS:000318788000020 PM 23584448 ER PT J AU Borodic, GE AF Borodic, Gary E. TI Use of Fillers as Adjunct Therapy for the Treatment of Lower Face Hemifacial Spasm SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Fall Scientific Symposium of the American-Society-of-Ophthalmic-Plastic-and-Reconstructive-Surgery (ASOPRS) CY OCT 21-22, 2011 CL Orlando, FL SP Amer Soc Ophthalm Plast & Reconstruct Surg (ASOPRS) AB The treatment of hemifacial spasm with periorbital injections of higher doses of botulinum toxin can create disfiguring and undesirable weakness in the lower face during active facial movements. The use of asymmetric hyaluronidate filler injections to the lower face provides a refinement allowing for a lowered neurotoxin dose. The filler creates a ballasting effect and involuntary facial movement. The conventional filler effect also further reduces asymmetric nasolabial folds and marionette lines. Fifteen of 18 patients with lower facial spasms found the filler toxin combination an improvement over neurotoxin alone. C1 [Borodic, Gary E.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Quincy, MA 02169 USA. RP Borodic, GE (reprint author), Harvard Univ, Sch Med, 1261 Furnace Brook Pkwy,Suite 15, Quincy, MA 02169 USA. EM borodic@aol.com NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2013 VL 29 IS 3 BP 225 EP 226 DI 10.1097/IOP.0b013e318289577e PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 142HM UT WOS:000318788000028 PM 23559346 ER PT J AU Yoon, MK McCulley, TJ AF Yoon, Michael K. McCulley, Timothy J. TI Secondary Tarsoconjunctival Graft: A Modification to the Cutler-Beard Procedure SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID UPPER EYELID RECONSTRUCTION; ACELLULAR DERMAL MATRIX; FREE TARSAL GRAFTS; HARD PALATE; SURGERY; SCLERA; FLAP AB Purpose: The Cutler-Beard procedure is a commonly used technique to reconstruct large upper eyelid defects. Eyelid retraction and entropion are common complications. To prevent these problems, the authors modified the traditional Cutler-Beard procedure with secondary placement of an autologous tarsoconjunctival graft. Methods: This is a retrospective review of 2 patients with large upper eyelid defects necessitating upper eyelid reconstruction. The initial stage is unaltered. At the time of flap division, a tarsoconjunctival graft from the contralateral upper eyelid is sutured to the posterior surface of the newly constructed upper eyelid. Two patients underwent this procedure, and follow up was 4 and 23 months, respectively. Patients developed no postoperative complications, including entropion or retraction. Conclusions: This modification to the Cutler-Beard operation is a technically simple procedure that can restore a more anatomically correct eyelid and can prevent subsequent entropion or retraction. This technique is unique, offering 3 major advances: first, placing the graft at the second surgical stage; second, replacing the tarsus and conjunctiva with like tissue; and third, preserving a lip of conjunctiva to cover the edge of the newly reconstructed upper eyelid. C1 [Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [McCulley, Timothy J.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA. [McCulley, Timothy J.] King Khalid Eye Specialist Hosp, Riyadh, Saudi Arabia. RP McCulley, TJ (reprint author), Johns Hopkins Sch Med, Wilmer Eye Inst, 660 North Wolfe St,Wilmer 110, Baltimore, MD 21287 USA. EM Tmccull5@jhmi.edu FU Research to Prevent Blindness Inc., New York, NY, U.S.A. FX Supported, in part, by an unrestricted grant to the Wilmer Ophthalmological Institute by Research to Prevent Blindness Inc., New York, NY, U.S.A. NR 24 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2013 VL 29 IS 3 BP 227 EP 230 DI 10.1097/IOP.0b013e3182831c84 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 142HM UT WOS:000318788000029 PM 23446299 ER PT J AU Gologorsky, D Jakobiec, FA Freitag, SK AF Gologorsky, Daniel Jakobiec, Frederick A. Freitag, Suzanne K. TI Transconjunctival Elimination of Keratin From an Intratarsal Meibomian Cyst SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TRANS-EPIDERMAL ELIMINATION; STEATOCYSTOMA SIMPLEX; DISORDERS; GLAND AB An unusual example of an intratarsal meibomian keratinous cyst is described in a 69-year-old man with spontaneous transepithelial (conjunctival) elimination. The lesion created an externally visible lump in the eyelid, which on eversion was found to be accompanied by yellow-whitish protruding material with a surrounding circular mound of reactive tissue. Excision revealed a large mass and smaller fragments of anuclear keratin (trichilemmal-type) embedded and sequestered in fibrous tissue with a granulomatous response. A re-excision was required because of persistent and irritating keratinous material, contrasting with the more indolent course of an uncomplicated epidermoid cyst of the eyelid dermis. This is the first documented instance of spontaneous rupture and extrusion of a meibomian tarsal cyst's keratin contents. C1 [Gologorsky, Daniel] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Jakobiec, Frederick A.; Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 14 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2013 VL 29 IS 3 BP E88 EP E91 DI 10.1097/IOP.0b013e3182771532 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 142HM UT WOS:000318788000009 PM 23250332 ER PT J AU Patel, MM Jakobiec, FA Zakka, FR Du, R Annino, DJ Borboli-Gerogiannis, S Daniels, AB AF Patel, Mrinali M. Jakobiec, Frederick A. Zakka, Fouad R. Du, Rose Annino, Donald J. Borboli-Gerogiannis, Sheila Daniels, Anthony B. TI Intraorbital Metastasis From Solitary Fibrous Tumor SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID OF-THE-LITERATURE; EXTRAOCULAR-MUSCLES; ORBIT; SYSTEM AB Solitary fibrous tumor (SFT) is a rare spindle cell tumor of mesenchymal origin that usually arises from pleura or pericardium but can also arise from many extraserosal sites. Although more than 50 cases of primary SFT of the orbit have been reported, there are no reports to date of a malignant nonophthalmic SFT metastasizing in the orbital soft tissues (although sphenoid wing bony involvement has been reported). The authors report here the first case of a patient with intraorbital metastasis of a CD34-positive malignant SFT. The patient was a 57-year-old man with a history of malignant pleural SFT and a prior kidney metastasis. He presented with the rapid appearance of proptosis and massive conjunctival chemosis preventing eyelid closure, and he was found to have a well-circumscribed metastasis to his lateral rectus muscle. Surgical excision cured his ocular symptoms, although he died 3 months later from brain and widespread metastases. C1 [Patel, Mrinali M.; Jakobiec, Frederick A.; Zakka, Fouad R.; Borboli-Gerogiannis, Sheila; Daniels, Anthony B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Du, Rose] Harvard Univ, Brigham & Womens Hosp, Dept Otorhinolaryngol, Sch Med, Boston, MA 02115 USA. [Annino, Donald J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Otorhinolaryngol, Boston, MA 02115 USA. RP Daniels, AB (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM anthony_daniels@meei.harvard.edu RI Du, Rose/I-5402-2012 OI Du, Rose/0000-0003-2641-6496 NR 24 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2013 VL 29 IS 3 BP E76 EP E79 DI 10.1097/IOP.0b013e318272f311 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 142HM UT WOS:000318788000004 PM 23328780 ER PT J AU Kumar, ATN AF Kumar, Anand T. N. TI Fluorescence lifetime detection in turbid media using spatial frequency domain filtering of time domain measurements SO OPTICS LETTERS LA English DT Article ID TOMOGRAPHY AB It is demonstrated that high spatial frequency filtering of time domain fluorescence signals can allow efficient detection of intrinsic fluorescence lifetimes from turbid media and the rejection of diffuse excitation leakage. The basis of this approach is the separation of diffuse fluorescence signals into diffuse and fluorescent components with distinct spatiotemporal behavior. (C) 2013 Optical Society of America C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu FU National Institutes of Health [R01 EB015325] FX The author thanks Simon Arridge for useful discussions. This work was supported by the National Institutes of Health, grant R01 EB015325. NR 9 TC 3 Z9 3 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAY 1 PY 2013 VL 38 IS 9 BP 1440 EP 1442 DI 10.1364/OL.38.001440 PG 3 WC Optics SC Optics GA 137HF UT WOS:000318425600027 PM 23632511 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI Carotid artery calcifications are a risk indicator for both myocardial infarction and stroke SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Letter C1 [Friedlander, Arthur H.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. NR 4 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 2212-4403 J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD MAY PY 2013 VL 115 IS 5 BP 700 EP 700 DI 10.1016/j.oooo.2013.02.003 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 139PL UT WOS:000318595700034 PM 23601227 ER PT J AU Losina, E Daigle, ME Suter, LG Hunter, DJ Solomon, DH Walensky, RP Jordan, JM Burbine, SA Paltiel, AD Katz, JN AF Losina, E. Daigle, M. E. Suter, L. G. Hunter, D. J. Solomon, D. H. Walensky, R. P. Jordan, J. M. Burbine, S. A. Paltiel, A. D. Katz, J. N. TI Disease-modifying drugs for knee osteoarthritis: can they be cost-effective? SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Knee osteoarthritis; Cost-effectiveness; Quality of life; Disease-modifying osteoarthritis drugs (DMOADs) ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; SURGEON PROCEDURE VOLUME; UNITED-STATES; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; HEALTH-STATUS; RISK; ASSOCIATION AB Objective: Disease-modifying osteoarthritis drugs (DMOADs) are under development. Our goal was to determine efficacy, toxicity, and cost thresholds under which DMOADs would be a cost-effective knee OA treatment. Design: We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare guideline-concordant care to strategies that insert DMOADs into the care sequence. The guideline-concordant care sequence included conservative pain management, corticosteroid injections, total knee replacement (TKR), and revision TKR. Base case DMOAD characteristics included: 50% chance of suspending progression in the first year (resumption rate of 10% thereafter) and 30% pain relief among those with suspended progression; 0.5%/year risk of major toxicity; and costs of $1,000/year. In sensitivity analyses, we varied suspended progression (20-100%), pain relief (10-100%), major toxicity (0.1-2%), and cost ($1,000-$7,000). Outcomes included costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs), and TKR utilization. Results: Base case DMOADs added 4.00 quality-adjusted life years (QALYs) and $230,000 per 100 persons, with an ICER of $57,500/QALY. DMOADs reduced need for TKR by 15%. Cost-effectiveness was most sensitive to likelihoods of suspended progression and pain relief. DMOADs costing $3,000/year achieved ICERs below $100,000/QALY if the likelihoods of suspended progression and pain relief were 20% and 70%. At a cost of $5,000, these ICERs were attained if the likelihoods of suspended progression and pain relief were both 60%. Conclusions: Cost, suspended progression, and pain relief are key drivers of value for DMOADs. Plausible combinations of these factors could reduce need for TKR and satisfy commonly cited cost-effectiveness criteria. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Losina, E.; Daigle, M. E.; Burbine, S. A.; Katz, J. N.] Brigham & Womens Hosp, Orthopaed & Arthrit Ctr Outcomes Res, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, E.; Solomon, D. H.; Katz, J. N.] Brigham & Womens Hosp, Sect Clin Sci, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Losina, E.; Solomon, D. H.; Walensky, R. P.; Katz, J. N.] Harvard Univ, Sch Med, Boston, MA USA. [Losina, E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Suter, L. G.; Paltiel, A. D.] Yale Univ, New Haven, CT USA. [Hunter, D. J.] Univ Sydney, Sydney, NSW 2006, Australia. [Walensky, R. P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jordan, J. M.] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA. RP Losina, E (reprint author), Brigham & Womens Hosp, Orthopaed & Arthrit Ctr Outcomes Res, 75 Francis St,OBC 1-4016, Boston, MA 02115 USA. EM elosina@partners.org; m.e.daigle@gmail.com; lisa.suter@yale.edu; david.hunter@sydney.edu.au; dsolomon@partners.org; rwalensky@partners.org; joanne_jordan@med.unc.edu; sara.burbine@gmail.com; david.paltiel@yale.edu; jnkatz@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIH/NIAMS [R01 AR053112, K24 AR057827]; VA Connecticut Healthcare System; Centers for Medicare 82 Medicaid Services, an Agency of the U.S. Department of Health and Human Services [HHSM-500-2008-0025I/HHSM-500-T0001] FX Supported by: NIH/NIAMS R01 AR053112, K24 AR057827, VA Connecticut Healthcare System (Dr. Suter), and Centers for Medicare 82 Medicaid Services, an Agency of the U.S. Department of Health and Human Services HHSM-500-2008-0025I/HHSM-500-T0001 (Dr. Suter). NR 66 TC 18 Z9 19 U1 0 U2 2 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 MAY PY 2013 VL 21 IS 5 BP 655 EP 667 DI 10.1016/j.joca.2013.01.016 PG 13 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 136UW UT WOS:000318389900003 PM 23380251 ER PT J AU Becker, SJE Bot, AGJ Curley, SE Jupiter, JB Ring, D AF Becker, S. J. E. Bot, A. G. J. Curley, S. E. Jupiter, J. B. Ring, D. TI A prospective randomized comparison of neoprene vs thermoplast hand-based thumb spica splinting for trapeziometacarpal arthrosis SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Trapeziometacarpal arthrosis; Thumb spica splint; Orthotics; Disability; Pain; Satisfaction ID 1ST CARPOMETACARPAL JOINT; CONTROLLED-TRIALS; OSTEOARTHRITIS; VALIDATION; SYMPTOMS; SCALE AB Objective: In patients with trapeziometacarpal arthrosis, we tested the hypothesis that there is no difference in arm-specific disability 5-15 weeks after prescription of a pre-fabricated neoprene or a custom-made thermoplast hand-based thumb spica splint with the metacarpophalangeal joint included and the first interphalangeal joint free. Method: One hundred nineteen patients with a diagnosis of trapeziometacarpal arthrosis were prospectively randomized to wear either a neoprene or a thermoplast hand-based thumb spica splint. At enrollment, patients completed a set of validated questionnaires. An average of 9 weeks later, patients returned for a second visit. Bivariable analyses assessed factors associated with disability, pain and satisfaction. Analysis was by intention-to-treat. Results: Sixty-two patients (32 with a neoprene and 30 with a thermoplast splint) completed the study, 51 patients (43%) did not return for the second visit, and six did not complete the protocol for other reasons. Non-completers were significantly younger than completers (P < 0.00044). On average completers rated the neoprene splint as more comfortable (P = 0.048), but there were no detectable differences in Disabilities of the Arm, Shoulder and Hand (DASH), change in DASH, pain, satisfaction, pinch or grip strength between the two splint types in our sample. Conclusion: When compared to custom-made thermoplast splints, pre-fabricated neoprene hand-based thumb spica splints are, on average, more comfortable, less expensive, and as effective in treating trapeziometacarpal arthrosis. This trial was registered at Clinicaltrials.gov (NCT00438763). (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Becker, S. J. E.; Bot, A. G. J.; Curley, S. E.; Jupiter, J. B.; Ring, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. RP Becker, SJE (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM sbecker1@partners.org; abot@partners.org; securley@partners.org; jjupiter1@partners.org; dring@partners.org RI Becker, Stephanie/N-5761-2014 FU Anna Foundation|NOREF; Genootschap Noorthey; Stichting Vreedefonds; Prins Bernhard Cultuurfonds/Banning-de Jong fonds; VSB-fonds FX SJEB is supported by Dutch research grants from Anna Foundation|NOREF, Genootschap Noorthey, and Stichting Vreedefonds for scientific research.; AGJB is supported by Dutch research grants from Anna Foundation|NOREF, Prins Bernhard Cultuurfonds/Banning-de Jong fonds, and VSB-fonds for scientific research. NR 20 TC 11 Z9 11 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD MAY PY 2013 VL 21 IS 5 BP 668 EP 675 DI 10.1016/j.joca.2013.02.006 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 136UW UT WOS:000318389900004 PM 23458785 ER PT J AU Stefanik, JJ Niu, J Gross, KD Roemer, FW Guermazi, A Felson, DT AF Stefanik, J. J. Niu, J. Gross, K. D. Roemer, F. W. Guermazi, A. Felson, D. T. TI Using magnetic resonance imaging to determine the compartmental prevalence of knee joint structural damage SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Osteoarthritis; Patellofemoral; Magnetic resonance imaging ID BONE-MARROW LESIONS; FRAMINGHAM OSTEOARTHRITIS; PATELLOFEMORAL JOINT; PAIN; MRI; CARTILAGE; ABNORMALITIES; LIMITATIONS AB Objective: To describe the prevalence of magnetic resonance imaging (MRI) detected structural damage in the patellofemoral joint (PFJ) and tibiofemoral joint (TFJ) in a population-based cohort. A secondary aim was to evaluate the patterns of compartmental involvement in knees with pain, between men and women, and in different age and body mass index (BMI) categories. Methods: We studied 970 knees, one knee per subject, from the Framingham Osteoarthritis Study, a population-based cohort study of persons 51-92 years old. Cartilage damage and bone marrow lesions (BMLs) were assessed using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The prevalence of isolated PFJ, isolated TFJ, and mixed structural damage was determined using the following definitions: any cartilage damage, full thickness cartilage loss, any BML, and the combination of full thickness cartilage loss with any BML. Results: The mean age and BMI was 63.4 years and 28.6 m/kg(2), respectively; 57% were female. Isolated PFJ damage occurred in 15-20% of knees and isolated TFJ damage occurred in 8-17% of knees depending on the definition used. The prevalence of isolated PFJ damage was greater than isolated TFJ damage using all definitions except the any BML definition. This pattern was similar between genders and among age and BMI categories. In those with knee pain, isolated PFJ was at least as common as TFJ damage depending on the definition used. Conclusion: Using MRI to assess knee joint structural damage, isolated PFJ damage was at least as common as, if not more common than, isolated TFJ damage. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Stefanik, J. J.; Niu, J.; Gross, K. D.; Roemer, F. W.; Guermazi, A.; Felson, D. T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gross, K. D.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Roemer, F. W.] Klinikum Augsburg, Augsburg, Germany. RP Stefanik, JJ (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, 650 Albany St,Suite 200, Boston, MA 02118 USA. EM stefanik@bu.edu; niujp@bu.edu; grossd@bu.edu; frank.roemer@klinikum-augsburg.de; ali.guermazi@bu.edu; dfelson@bu.edu OI Felson, David/0000-0002-2668-2447; Niu, Jingbo/0000-0002-6170-1965 FU Arthritis Foundation; NIH [T32AR007598, R01AG009300, P60AR020613, R01AG018393, P60AR047785]; Genzyme; Stryker; Merck Serono; Novartis; Astra Zeneca; National Institutes of Health FX Dr Stefanik's work was supported by a Postdoctoral Fellowship from the Arthritis Foundation and NIH grant T32AR007598. The Framingham Osteoarthritis Study was supported by NIH grants R01AG009300, P60AR020613, and R01AG018393. Drs. Stefanik, Niu, Gross, and Felson were also supported by NIH grant P60AR047785.; Dr Guermazi has received consultancies, speaking fees, and/or honoraria from Genzyme, Stryker, Merck Serono, Novartis and Astra Zeneca. He is the President of Boston Imaging Core Lab (BICL), a company providing image assessment services. Dr Roemer is Chief Medical Officer and shareholder of BICL and has received consultancies, speaking fees, and/or honoraria from Merck Serono and the National Institutes of Health. NR 21 TC 19 Z9 19 U1 2 U2 7 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 MAY PY 2013 VL 21 IS 5 BP 695 EP 699 DI 10.1016/j.joca.2013.02.003 PG 5 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 136UW UT WOS:000318389900008 PM 23428598 ER PT J AU Lee, JH Kirkham, JC McCormack, MC Nicholls, AM Randolph, MA Austen, WG AF Lee, Jeffrey H. Kirkham, John C. McCormack, Michael C. Nicholls, Alexa M. Randolph, Mark A. Austen, William G., Jr. TI The Effect of Pressure and Shear on Autologous Fat Grafting SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CELL-ASSISTED LIPOTRANSFER; VIABILITY; BREAST; TRANSPLANTATION; SURVIVAL; HARVEST; CORRECT AB Background: Fat grafting has become routine in plastic surgery because of low donor-site morbidity, a low complication rate, and fast recovery time. The optimal technique, however, has yet to be defined. Two critical variables are pressure and shear, both defined as force divided by area. In this study, the authors examined the effect of pressure and shear on human fat grafts in a nude mouse model. Methods: For negative pressure, tumescent liposuction was performed on fresh panniculectomy specimens. Suction pressure was either -15 inHg or -25 inHg. Lipoaspirate was centrifuged at 1200 g and injected into the flanks of nude mice. For positive pressure, positive pressure was applied to lipoaspirate up to 6 atm for up to 3 minutes and then injected into nude mice. For shear stress, lipoaspirate was centrifuged at 1200 g for 3 minutes and then injected with a fast flow rate (3 to 5 cc/second) or slow flow rate (0.5 to 1 cc/second). After 4 weeks, the fat grafts were analyzed for weight and histology. Results: For negative pressure, there were no differences in weight or histology with high versus low suction pressures. For positive pressure, application of positive pressures up to 6 atm for up to 3 minutes did not create a significant difference in graft weight or histology at 4 weeks. For shear stress, in vivo, a slow injection pressure yielded a 38 percent increase in weight (p < 0.001) compared with fast injection. Histology was similarly affected. Conclusions: Higher aspiration pressures up to -0.83 atm did not affect fat graft viability in vivo. Positive pressure up to 6 atm also did not affect fat graft viability. The degree of shear stress, which is a function of flow rate, did significantly affect fat graft viability. Fat grafts injected slowly with low shear stress significantly outperformed fat injected with high shear stress. These data suggest that shear stress is a more important variable regarding fat graft viability than pressure. C1 [Lee, Jeffrey H.; Kirkham, John C.; McCormack, Michael C.; Nicholls, Alexa M.; Randolph, Mark A.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org FU LifeCell Corp. FX This research was partially funded by a research grant from LifeCell Corp. All research was conducted independently within facilities at the Massachusetts General Hospital. NR 25 TC 39 Z9 39 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2013 VL 131 IS 5 BP 1125 EP 1136 DI 10.1097/PRS.0b013e3182879f4a PG 12 WC Surgery SC Surgery GA 138WG UT WOS:000318540700062 PM 23385989 ER PT J AU Elderon, L Whooley, MA AF Elderon, Larkin Whooley, Mary A. TI Depression and Cardiovascular Disease SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Cardiovascular disease; Major depressive disorder; Health-related behaviors; Diagnosis; Treatment ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; RANDOMIZED-CONTROLLED-TRIAL; QUALITY IMPROVEMENT STRATEGIES; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY; INFLAMMATORY MARKERS; MAJOR DEPRESSION C1 [Elderon, Larkin] Univ Calif San Francisco, Sch Med, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Sch Med, Dept Epidemiol, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Sch Med, Dept Biostat, San Francisco, CA 94121 USA. [Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Whooley, MA (reprint author), Univ Calif San Francisco, Dept Vet Affairs Med Ctr, 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM mary.whooley@ucsf.edu OI Elderon, Larkin/0000-0002-9620-7756 NR 136 TC 40 Z9 41 U1 4 U2 28 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAY-JUN PY 2013 VL 55 IS 6 BP 511 EP 523 DI 10.1016/j.pcad.2013.03.010 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 140OO UT WOS:000318665000002 PM 23621961 ER PT J AU Edmondson, D Cohen, BE AF Edmondson, Donald Cohen, Beth E. TI Posttraumatic Stress Disorder and Cardiovascular Disease SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Posttraumatic stress disorder; Cardiovascular disease; Myocardial infarction; Acute coronary syndrome; Stroke; Psychosocial risk factors ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION PATIENTS; NATIONAL COMORBIDITY SURVEY; QUALITY-OF-LIFE; BREAST-CANCER; MENTAL-DISORDERS; SLEEP DISTURBANCES; HEALTH BEHAVIORS C1 [Edmondson, Donald] Columbia Univ, Med Ctr, Dept Med, Ctr Behav Cardiovasc Hlth, New York, NY 10032 USA. [Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Edmondson, D (reprint author), Columbia Univ, Med Ctr, 622W 168th St,PH9-317, New York, NY 10032 USA. EM dee2109@columbia.edu RI Edmondson, Donald/G-7486-2016 FU National Institutes of Health, Bethesda, Maryland, United States [HL-088117, CA-156709]; Columbia University's CTSA from the National Institutes of Health, Bethesda, Maryland, United States [UL1RR024156]; National Institutes of Health, Bethesda, MD, USA [K23 HL 094765] FX This work was supported by grants HL-088117 and CA-156709, and in part by Columbia University's CTSA grant No.UL1RR024156, from the National Institutes of Health, Bethesda, Maryland, United States. Dr. Cohen was supported by grant K23 HL 094765 from the National Institutes of Health, Bethesda, MD, USA. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the National Institutes of Health. NR 104 TC 32 Z9 32 U1 9 U2 21 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAY-JUN PY 2013 VL 55 IS 6 BP 548 EP 556 DI 10.1016/j.pcad.2013.03.004 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 140OO UT WOS:000318665000005 PM 23621964 ER PT J AU Dong, QX Wang, DH Bandyopadhyay, A Gao, H Gorena, KM Hildreth, K Rebel, VI Walter, CA Huang, CJ Sun, LZ AF Dong, Qiaoxiang Wang, Danhan Bandyopadhyay, Abhik Gao, Hui Gorena, Karla M. Hildreth, Kim Rebel, Vivienne I. Walter, Christi A. Huang, Changjiang Sun, Lu-Zhe TI Mammospheres from murine mammary stem cell-enriched basal cells: Clonal characteristics and repopulating potential SO STEM CELL RESEARCH LA English DT Article ID NEUROSPHERE ASSAY; NEURAL STEM; GLAND; POPULATION; PROGENITOR AB Identification of murine mammary stem cells (MaSCs) has been attempted with various in vitro and in vivo assays. While, the in vivo repopulation assay remains as the most definitive assay for MaSC detection, it is expensive, time-consuming, and technically challenging. The in vitro mammosphere assay was considered unreliable because of major concerns about its clonal origin. In the current study, co-culture experiments with mammary cells from fluorescent protein transgenic mice and time-lapse video microscopy revealed that >90% mammospheres formed from sorted basal epithelial-enriched cells were of clonal origin in terms of stem cell. These basal-cell derived mammospheres were further distinguished morphologically in a 3-dimensional extracellular matrix culture and functionally in the in vivo repopulation assay. Transplant of single mammospheres or the resultant 3-dimensional solid structures into gland-free mammary fat pads yielded a 70% success rate of multilineage mammary gland reconstitution. Thus, this in vitro sphere formation and differentiation assay is a reliable alternative to the in vivo repopulation assay for the study of MaSCs. (C) 2013 Elsevier B.V. All rights reserved. C1 [Dong, Qiaoxiang; Bandyopadhyay, Abhik; Hildreth, Kim; Rebel, Vivienne I.; Walter, Christi A.; Sun, Lu-Zhe] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78299 USA. [Dong, Qiaoxiang; Wang, Danhan; Gao, Hui; Huang, Changjiang; Sun, Lu-Zhe] Wenzhou Med Coll, Sch Environm Sci & Publ Hlth, Univ Town, Wenzhou, Peoples R China. [Bandyopadhyay, Abhik; Rebel, Vivienne I.; Walter, Christi A.; Sun, Lu-Zhe] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78299 USA. [Rebel, Vivienne I.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78299 USA. [Walter, Christi A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Dong, QX (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78299 USA. EM dongq2@uthscsa.edu; sunl@uthscsa.edu RI Huang, Changjiang/F-2644-2010; Dong, Qiaoxiang/F-1918-2010; OI Dong, Qiaoxiang/0000-0003-4003-7919 FU NIH [R01CA75253, R01ES022057]; Bank of America Shelby Rae Tengg Foundation; Mary Kay Foundation [082-12]; Cancer Therapy and Research Center at University of Texas Health Science Center at San Antonio through the NCI Cancer Center [2P30CA054174-17] FX This work was supported in part by funding from NIH Grants R01CA75253 and R01ES022057, the Bank of America Shelby Rae Tengg Foundation, the Mary Kay Foundation (#082-12), and the Cancer Therapy and Research Center at University of Texas Health Science Center at San Antonio through the NCI Cancer Center Support Grant 2P30CA054174-17 to the flow cytometry core facility. We thank Dr. John Stingl for his kind instruction in establishing the in vitro and in vivo assays in our laboratory. We also thank Dr. Rong Li for the use of the Nikon BioStation-IM. NR 17 TC 10 Z9 11 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD MAY PY 2013 VL 10 IS 3 BP 396 EP 404 DI 10.1016/j.scr.2013.01.007 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 135ZY UT WOS:000318330400012 PM 23466563 ER PT J AU Surman, CBH Hammerness, PG Petty, C Spencer, T Doyle, R Napolean, S Chu, N Yorks, D Biederman, J AF Surman, Craig B. H. Hammerness, Paul G. Petty, Carter Spencer, Thomas Doyle, Robert Napolean, Siena Chu, Nicole Yorks, Dayna Biederman, Joseph TI A pilot open label prospective study of memantine monotherapy in adults with ADHD SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; adults; memantine; psychopharmacology; cognition ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION DEFICITS; FOLLOW-UP; DOPAMINE; PREVALENCE; IMPAIRMENTS; PERFORMANCE; MODULATION; TASK AB Objectives. Available pharmacotherapies treat some adults with ADHD inadequately. A small literature suggests that glutamate modulation could have effects on ADHD. Methods. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, was titrated to a maximum dose of 10 mg BID in 34 adult subjects aged 18-55 who met DSM-IV criteria for ADHD or ADHD NOS on structured interview. Twenty-eight subjects completed 12 weeks exposure. The Adult ADHD Investigator Symptom Report (AISRS), Clinical Global Impression (CGI), a neuropsychological battery sensitive to domains of executive function, and the CANTAB cognitive battery were administered. Paired t-tests compared treated and baseline scores. Results. At week 12, AISRS data showed reduction in total symptoms (-17.5, P < 0.001), inattentive symptoms (-10.6, P < 0.001), and hyperactive symptoms (-6.9, P < 0.01). A total of 44% of subjects had CGI ratings of much or very much improved. Cognitive performance improved in measures of attention, working memory, and other selected executive domains by weeks 6 and 12 (each P < 0.05); simple reaction time declined by week 12 (P < 0.05). There were no severe adverse events, but mild adverse events were common and six subjects discontinued due to adverse effects. Conclusions. Memantine was largely well-tolerated and associated with improvement in ADHD symptoms and neuropsychological performance. Randomized studies are indicated to confirm whether memantine is a novel therapy for ADHD across the lifespan. C1 [Surman, Craig B. H.; Hammerness, Paul G.; Petty, Carter; Spencer, Thomas; Doyle, Robert; Napolean, Siena; Chu, Nicole; Yorks, Dayna; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Surman, Craig B. H.; Hammerness, Paul G.; Spencer, Thomas; Doyle, Robert; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Suite 2000 185 Alewife Brook Pkwy, Cambridge, MA 02138 USA. EM csurman@partners.org FU Abbott; Alza; Cephalon; Eli Lilly; ElMinda the Hilda and Preston Davis Foundation; McNeil; Merck; New River; Nordic Naturals National Institutes of Health; Organon; Pfizer; Shire; Takeda; Forest; Elminda Ltd; Bristol Myers Squibb; Glaxo-SmithKline; Johnson Johnson; Elminda; MGH Psychiatry Academy; Department of Psychiatry at MGH; Fundacion Dr. Manuel Camelo A. C. in Monterrey Mexico; AstraZeneca; Boston University; Celltech; Eli Lilly and Co.; Esai; Fundacion Areces (Spain); Glaxo; Gliatech; Hastings Center; Janssen; Medice Pharmaceuticals (Germany); MMC Pediatric; NARSAD; NIDA; NICHD; NIMH; Novartis; Noven; Neurosearch; Otsuka; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry Association; Stanley Foundation; UCB Pharma Inc.; Veritas; Wyeth; Pediatric Psychopharmacology Council FX Dr Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, ElMinda the Hilda and Preston Davis Foundation, McNeil, Merck, New River, Nordic Naturals National Institutes of Health, Organon, Pfizer, Shire, and Takeda; has been a speaker for Janssen-Ortho, McNeil, Novartis, Shire, and MGH Academy/Reed Medical Education (which received funding from multiple pharmaceutical companies); and has been a consultant/advisor for McNeil, Shire, Somaxon and Takeda.; In the past 2 years, Dr Hammerness has received research funds or participated in CME activities/professional talks supported by the following pharmaceutical companies: Abbott, Eli Lilly, Forest, McNeil, Shire. Dr Hammerness has also received research funds from Elminda Ltd and has participated in speaker training and served on the advisory board for Shire. In the past 2 years, Dr Hammerness has participated, as an investigator, in research studies funded by the following pharmaceutical companies: Abbott, Bristol Myers Squibb, Cephalon, Eli Lilly, Glaxo-SmithKline, Johnson & Johnson, McNeil, Merck, New River, Organon, Pfizer, Shire, Takeda. Dr Hammerness has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's website, www.mghcme.org.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire.; In 2011, Dr. Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, and received an honorarium for presenting at an international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received depart mental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH.; In 2010, Dr. Joseph Biederman received a speaker's fee from a single talk given at Fundacion Dr. Manuel Camelo A. C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition- funded CME course.; In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/ from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Fundacion Areces (Spain), Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth.; This work has been funded in part by the Pediatric Psychopharmacology Council. NR 40 TC 8 Z9 10 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1562-2975 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PD MAY PY 2013 VL 14 IS 4 BP 291 EP 298 DI 10.3109/15622975.2011.623716 PG 8 WC Psychiatry SC Psychiatry GA 140JR UT WOS:000318650900006 PM 22436083 ER PT J AU Hammerness, P Zusman, R Systrom, D Surman, C Baggish, A Schillinger, M Shelley-Abrahamson, R Wilens, TE AF Hammerness, Paul Zusman, Randall Systrom, David Surman, Craig Baggish, Aaron Schillinger, Mary Shelley-Abrahamson, Rachel Wilens, Timothy E. TI A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE Cardiac; cardiopulmonary; lisdexamfetamine; ADHD; stimulant ID SERIOUS CARDIOVASCULAR EVENTS; HEART-RATE RECOVERY; BLOOD-PRESSURE; FOLLOW-UP; ADHD; RECOMMENDATIONS; STIMULANTS; PREVALENCE; CHILDREN; DEATH AB Objectives. Due to concerns about the safety of stimulants for ADHD, novel assessments of the cardiopulmonary impact of these agents are needed. Methods. An open design of lisdexamfetamine (LDX) in 15 adults with DSM-IV ADHD. Following a psychiatric evaluation and medical history, subjects underwent echocardiography (TTE) and cardiopulmonary exercise testing (CPET). LDX was titrated to 70 mg daily over 6 weeks, followed by monthly visits to 6 months. Change in TTE and CPET measures were examined following up to 6 months of LDX. Results. At endpoint, there were no significant alterations in indices of cardiac systolic performance, or in metabolic and ventilatory variables at maximum exertion (P values > 0.05). We found significant mean changes in resting LV systolic dimension and Doppler diastolic indices. Change in heart rate recovery at 1 min met statistical significance (P = 0.05). Conclusions. We did not detect clinically meaningful changes in cardiac structure and function or in metabolic and ventilatory variables at maximum exertion in ADHD adults receiving open LDX. The clinical significance of changes in resting LV dimension and indices of diastolic function are not in the direction of cardiomyopathy. Future large sample controlled study can examine these findings, as well as stimulants' impact on heart rate recovery. C1 [Hammerness, Paul; Surman, Craig; Schillinger, Mary; Shelley-Abrahamson, Rachel; Wilens, Timothy E.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Cambridge, MA USA. [Zusman, Randall; Baggish, Aaron] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Systrom, David] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. RP Hammerness, P (reprint author), 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org OI Systrom, David/0000-0002-9610-6330 FU Shire Pharmaceutical; Cephalon; Forest; GlaxoSmithKline; Johnson Johnson; McNeil; Novartis; Ortho-McNeil Janssen; Shire; Takeda Pharmaceuticals; Elminda Ltd.; Abbott; Alza; Eli Lilly; Hilda and Preston Davis Foundation; Merck; New River; Nordic Naturals; Organon; Pfizer; Takeda; Lilly; Shire Pharma FX Source of Funding: Investigator Initiated Study funded by Shire Pharmaceutical (P. Hammerness, PI). Dr. Hammerness: in the past 12 months, Dr Hammerness has participated in CME activities/writing supported by Shire Pharmaceuticals. Dr Hammerness has participated, as an investigator/principal investigator, in research studies funded by the following companies: Cephalon, Forest, GlaxoSmithKline, Johnson & Johnson, McNeil, Novartis, Ortho-McNeil Janssen, Shire, Takeda Pharmaceuticals and Elminda Ltd. Dr Hammerness has also received honoraria from commercial entities supporting the MGH Psychiatry Academy, www.mghcme.org. Dr Zusman: no disclosures related to this project. Dr Systrom: No disclosures related to this project. Dr Surman has received research support from the following: Abbott, Alza, Cephalon, Eli Lilly, the Hilda and Preston Davis Foundation, McNeil, Merck, New River, Nordic Naturals, Organon, Pfizer, Shire, and Takeda; has been a speaker for Janssen-Ortho, McNeil, Novartis, and Shire; and has been a consultant/advisor to McNeil, Shire, Somaxon and Takeda. Dr Baggish, Ms Schillinger and Ms Shelley-Abrahamson: no disclosures related to this project. Dr Wilens receives or has received grant support from: Abbott, McNeil, Lilly, Merck, and Shire Pharma. Dr Wilens has been a speaker for the following companies: Lilly, McNeil, Novartis, Shire Pharma. Dr Wilens is or has been a consultant for: Abbott, Astra-Zeneca, Euthymics, McNeil, Lilly, NIH, Novartis, Merck, Shire Pharma. Dr Wilens has a published book with Guilford Press. NR 34 TC 5 Z9 5 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1562-2975 EI 1814-1412 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PD MAY PY 2013 VL 14 IS 4 BP 299 EP 306 DI 10.3109/15622975.2012.678884 PG 8 WC Psychiatry SC Psychiatry GA 140JR UT WOS:000318650900007 PM 22559155 ER PT J AU Coverdale, JH Balon, R Beresin, EV Louie, AK Tait, GR Roberts, LW AF Coverdale, John H. Balon, Richard Beresin, Eugene V. Louie, Alan K. Tait, Glendon R. Roberts, Laura W. TI An Argument for Conducting Methodologically Strong, Randomized, Controlled Trials in Educational Research SO ACADEMIC PSYCHIATRY LA English DT Editorial Material ID MEDICAL-EDUCATION; CRITICAL-APPRAISAL; CLINICAL-TRIALS; READERS GUIDE; DESIGN; QUALITY; COHORT C1 [Coverdale, John H.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Balon, Richard] Univ Psychiat Centrum St Jozef, Detroit, MI USA. [Beresin, Eugene V.] Harvard Univ, Dept Psychiat, Mass Gen Hosp, Boston, MA 02115 USA. [Louie, Alan K.; Roberts, Laura W.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Tait, Glendon R.] Univ Toronto, Toronto Gen Hosp, Dept Psychiat, Toronto, ON M5G 1L7, Canada. RP Coverdale, JH (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. EM jhc@bcm.tmc.edu NR 33 TC 1 Z9 1 U1 1 U2 3 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 MAY-JUN PY 2013 VL 37 IS 3 BP 145 EP 149 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 137SY UT WOS:000318459000001 PM 23632922 ER PT J AU Axelrad, JE Mimiaga, MJ Grasso, C Mayer, KH AF Axelrad, Jordan E. Mimiaga, Matthew J. Grasso, Chris Mayer, Kenneth H. TI Trends in the Spectrum of Engagement in HIV Care and Subsequent Clinical Outcomes Among Men Who Have Sex with Men (MSM) at a Boston Community Health Center SO AIDS PATIENT CARE AND STDS LA English DT Article ID UNITED-STATES; ANTIRETROVIRAL THERAPY; INFECTED PERSONS; MEDICAL-CARE; PREVENTION; HIV/AIDS; PREVALENCE; DIAGNOSIS; SETTINGS AB Despite known benefits, only 19-28% of HIV-infected Americans are virologically suppressed (defined as <= 200 copies/mL). Engagement in HIV care represents a continuum from patients unaware they are infected to virological suppression. The electronic medical record of all newly diagnosed HIV-infected MSM seen at Fenway Health between 2000 and 2010 were reviewed. Patients were "engaged'' if they had one negative HIV test and/or one physical exam within 24 months prior to their HIV diagnosis (n = 291). All others were considered "new'' (n = 463). MSM engaged in care prior to HIV diagnosis were more often identified in acute retroviral syndrome or on routine screening, more rapidly linked to care, and less often diagnosed with a concomitant STI than those who were not engaged in care. Nearly 19% of all patients were diagnosed with AIDS the same time they were diagnosed with HIV. Blacks and those with higher CD4 counts at diagnosis were less likely to be virologically suppressed at 1 year. Between 2000 and 2010, patients retained in care were more likely to initiate ART and be virologically suppressed within 1 year independent of initial HIV viral load and CD4 count. Engagement in care prior to seroconversion influences important HIV outcomes. Programs that care for at risk populations should institute routine opt-out HIV testing and test-and-treat programs to optimize HIV care and prevention. C1 [Axelrad, Jordan E.; Mimiaga, Matthew J.; Grasso, Chris; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Axelrad, Jordan E.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Axelrad, Jordan E.] Mt Sinai Hosp, Dept Internal Med, New York, NY 10029 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis, Boston, MA 02215 USA. RP Axelrad, JE (reprint author), Mt Sinai Hosp, Dept Med, Box 1118 1 Gustave L Levy Pl, New York, NY 10029 USA. EM Jordan.Axelrad@mountsinai.org OI Axelrad, Jordan/0000-0003-1951-7790 FU Harvard Center for AIDS Research [NIAID 5P30AI06354-08] FX Sources of support: Harvard Center for AIDS Research (NIAID 5P30AI06354-08). NR 32 TC 15 Z9 15 U1 3 U2 7 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 MAY PY 2013 VL 27 IS 5 BP 287 EP 296 DI 10.1089/apc.2012.0471 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 138YA UT WOS:000318546600005 PM 23651106 ER PT J AU Peyko, V Cohen, V Jellinek-Cohen, SP Pearl-Davis, M AF Peyko, Vincent Cohen, Victor Jellinek-Cohen, Samantha P. Pearl-Davis, Michelle TI Evaluation and treatment of accidental autoinjection of epinephrine SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID ADRENALINE; INJECTION; ISCHEMIA AB Purpose. A case of accidental autoinjection. of epinephrine is described. Summary. A 47-year-old man arrived at the emergency department after accidental injection of epinephrine with an autoinjector into his left thumb. His vital signs were stable at admission. The patient was allergic to nuts and thought he may have eaten something containing a pine nut, The patient reported feeling itching in his throat but had no shortness of breath or swollen tongue. He tried to self-administer an epinephrine injection, but it did not inject. While he was checking the device, it accidently injected into his left thumb pad. A review of systems revealed throat discomfort, a tingling sensation of the tongue, and a left-thumb puncture with pain. Physical examination of the left thumb pad revealed a pale, cool thumb with diminished capillary refill and punctuate black discoloration at the site of injection. Topical nitroglycerin paste was applied but had no effect, so terbutaline was ordered. The terbutaline injection was prepared as a 1:1 preparation of terbutaline sulfate 1 mg/mL and 0.9% sodium chloride injection. The immediate effects were the return of color from pale white to red and observable perfusion to the area within seconds. After 20 minutes, the red color remained, with observable perfusion and warmth, in addition to complete neurosensory function. Sixty minutes after terbutaline administration, the patient was discharged home. Conclusion. A 47-year-old man who accidentally injected himself in the thumb with an epinephrine autoinjector was successfully treated with subcutaneous terbutaline. The treatment had an immediate effect, including revascularization and resolution of pain. C1 [Peyko, Vincent] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Peyko, Vincent] Maimonides Hosp, Dept Pharmaceut Serv, Brooklyn, NY 11219 USA. [Cohen, Victor] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Brooklyn, NY USA. [Jellinek-Cohen, Samantha P.] St Johns Univ, Coll Pharm & Hlth Sci, Queens, NY 11439 USA. [Pearl-Davis, Michelle] Maimonides Hosp, Dept Emergency Med, Brooklyn, NY 11219 USA. RP Jellinek-Cohen, SP (reprint author), St Johns Univ, Coll Pharm & Hlth Sci, 8000 Utopia Pkwy, Queens, NY 11439 USA. EM jellines@stjohns.edu NR 15 TC 3 Z9 3 U1 0 U2 3 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 MAY 1 PY 2013 VL 70 IS 9 BP 778 EP 781 DI 10.2146/ajhp120316 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 137WQ UT WOS:000318469300010 PM 23592360 ER PT J AU Stroupe, KT Smith, BM Hogan, TP St Andre, JR Gellad, WF Weiner, S Lee, TA Burk, M Cunningham, F Piette, JD Rogers, TJ Huo, ZP Weaver, FM AF Stroupe, Kevin T. Smith, Bridget M. Hogan, Timothy P. St Andre, Justin R. Gellad, Walid F. Weiner, Saul Lee, Todd A. Burk, Muriel Cunningham, Francesca Piette, John D. Rogers, Thea J. Huo, Zhiping Weaver, Frances M. TI Medication acquisition across systems of care and patient-provider communication among older veterans SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID HEALTH-CARE; HEART-FAILURE; ADULTS; DISCREPANCIES; HYPERTENSION; INFORMATION; OUTCOMES; COSTS AB Purpose. The results of a survey assessing Medicare Part D enrollment, the use of pharmacotherapies for chronic diseases, and other medication-use issues in a population of elderly military veterans are presented. Methods. Medicare-eligible (i.e., >= 65 years of age) patients with documented recent service use at a single Veterans Affairs (VA) medical center were targeted for a mail survey. Women were oversampled (20%) to ensure an adequate sample size; the sample was weighted to adjust for this oversampling. Usable survey data were received from 458 survey respondents. Results. Nearly all respondents (93.2%) reported having one or more chronic conditions; of those, 93.3% reported regular use of multiple drug therapies, and 30.1% reported using medications prescribed by both VA and non-VA providers for the same chronic condition. About half of the survey respondents reported at least one office visit with a non-VA physician during the previous year, and 55.8% reported obtaining medications from non-VA pharmacies. More than half (54.1%) of the respondents reported non-VA medication coverage, with 21.2% indicating they were enrolled in Medicare Part D. Among the respondents who reported obtaining medications from non-VA pharmacies, substantial proportions reported discussing those medications with VA physicians never (38.4%) or infrequently (15.7%). Conclusion. Although large proportions of Medicare-eligible veterans take multiple medications and use non-VA health care services and pharmacies, many do not discuss medications obtained outside the VA system with VA physicians, suggesting that increased efforts to enhance provider patient communication and medication reconciliation across VA and non-VA systems of care may be warranted. C1 [Stroupe, Kevin T.; Smith, Bridget M.] Edward Hines Jr VA Vet Affairs Hosp, Ctr Management Complex Chron Care CMC3, Hines, IL USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, Natl eHlth QUERI Coordinating Ctr, eHlth Qual Enhancement Res Initiat QUERI, Bedford, MA USA. [St Andre, Justin R.] Hlth Res & Educ Trust, Chicago, IL USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Lee, Todd A.] Univ Illinois, Chicago, IL USA. [Cunningham, Francesca] Edward Hines Jr VA Hosp, VA Pharm Benefit Management Strateg Healthcare Gr, Hines, IL 60141 USA. [Piette, John D.] Univ Michigan, Ctr Clin Management Res, Ann Arbor, MI 48109 USA. RP Stroupe, KT (reprint author), Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, 5000 South 5th Ave 151H, Hines, IL 60141 USA. EM kevin.stroupe@va.gov FU Office of Research and Development, Veterans Health Administration, Department of Veterans Affairs; Center for Management of Complex Chronic Care, Edward Hines, Jr. VA Hospital; VA Health Services Research and Development [PPO 09-396] FX Supported in part by the Office of Research and Development, Veterans Health Administration, Department of Veterans Affairs; the Center for Management of Complex Chronic Care, Edward Hines, Jr. VA Hospital; and VA Health Services Research and Development grant PPO 09-396. NR 31 TC 6 Z9 6 U1 0 U2 7 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 MAY 1 PY 2013 VL 70 IS 9 BP 804 EP 813 DI 10.2146/ajhp120222 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 137WQ UT WOS:000318469300013 PM 23592363 ER PT J AU Glasgow, JM Yano, EM Kaboli, PJ AF Glasgow, Justin M. Yano, Elizabeth M. Kaboli, Peter J. TI Impacts of Organizational Context on Quality Improvement SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE quality improvement; data mining; organizational characteristics; Veterans Affairs ID OF-THE-LITERATURE; PATIENT SAFETY; HEALTH-CARE; MODEL; COLLABORATIVES; HOSPITALS; SUCCESS AB Variation in how hospitals perform on similar quality improvement (QI) efforts argues for a need to understand how different organizational characteristics affect QI performance. The objective of this study was to use data-mining methods to evaluate relationships between measures of organizational characteristics and hospital QI performance. Organizational characteristics were extracted from 2 surveys and analyzed in 3 separate decision-tree models.The decision trees did not find any predictive associations in this sample of 100 hospitals participating in a national QI collaborative. Further model review identified that measures of QI Experience were associated with an ability to make improvements, whereas measures of Staffing and Culture were associated with an ability to sustain improvements. A key area for future research is to understand the challenges faced as QI teams transition from improving care to sustaining quality and to ascertain what organizational characteristics can best overcome those challenges. C1 [Glasgow, Justin M.; Kaboli, Peter J.] Iowa City VA Healthcare Syst, Iowa City, IA 52246 USA. [Glasgow, Justin M.] Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA USA. [Yano, Elizabeth M.] VA Greater Los Angeles, Ctr Excellence Study Healthcare Provider Behav, Sepulveda, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Kaboli, Peter J.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. RP Glasgow, JM (reprint author), Iowa City VA Healthcare Syst, 601 Highway 6 West,Mailstop 152, Iowa City, IA 52246 USA. EM justin.glasgow@va.gov FU University of Iowa Institute for Clinical and Translational Science [5TL1 RR024981-03]; Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development (HSR&D) Service through the Comprehensive Access and Delivery Research and Evaluation (CADRE) Center [HFP 04-149]; Veterans Administration (VA) HSR&D Research Career Scientist Award [RCS 05-195]; VA HSRD; VA Office of Quality and Performance FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work reported here was supported by a TL1 award from the University of Iowa Institute for Clinical and Translational Science (5TL1 RR024981-03) and the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Service through the Comprehensive Access and Delivery Research and Evaluation (CADRE) Center (HFP 04-149). Dr Yano's effort was funded by a Veterans Administration (VA) HSR&D Research Career Scientist Award (RCS 05-195). The VA Clinical Practice Organizational Survey was cosponsored by VA HSR&D and the VA Office of Quality and Performance. NR 29 TC 4 Z9 4 U1 3 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAY-JUN PY 2013 VL 28 IS 3 BP 196 EP 205 DI 10.1177/1062860612456730 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 136QY UT WOS:000318379700002 PM 22942122 ER PT J AU Chen, Q Borzecki, AM Cevasco, M Shin, MH Shwartz, M Itani, KMF Rosen, AK AF Chen, Qi Borzecki, Ann M. Cevasco, Marisa Shin, Marlena H. Shwartz, Michael Itani, Kamal M. F. Rosen, Amy K. TI Examining the Relationship Between Processes of Care and Selected AHRQ Patient Safety Indicators Postoperative Wound Dehiscence and Accidental Puncture or Laceration Using the VA Electronic Medical Record SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE AHRQ Patient Safety Indicators; processes of care; postoperative wound dehiscence; accidental puncture or laceration ID REFLECT DIFFERENCES; QUALITY INDICATORS; IATROGENIC DISEASE; PLEURAL PROCEDURES; VETERANS; SURGERY; COMPLICATIONS; TIME; EXPLICIT; EVENTS AB This study examines whether Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs) Postoperative Wound Dehiscence (PWD) and Accidental Puncture or Laceration (APL) events reflect problems with hospital processes of care (POC).The authors randomly selected 112 PSI-flagged PWD/APL discharges from 2002-2007 VA administrative data, identified true cases using chart review, and matched cases with controls.This yielded a total of 95 case-control pairs per PSI. Patient information and clinical processes on each case-control pair were abstracted from the electronic medical record (EMR).Although PWD cases and controls differed on incision and closure types,APL cases and controls were comparable in examined processes. Further exploration of the process differences between PWD cases and controls indicated that they were primarily caused by patients' underlying surgical problems rather than quality of care shortfalls. Documentation of POC was frequently missing in EMRs. Future studies should combine EMR review with alternative approaches, such as direct observation, to better assess POC. C1 [Chen, Qi; Cevasco, Marisa; Shin, Marlena H.; Shwartz, Michael; Itani, Kamal M. F.; Rosen, Amy K.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Chen, Qi; Borzecki, Ann M.; Shwartz, Michael; Itani, Kamal M. F.; Rosen, Amy K.] Boston Univ, Boston, MA 02215 USA. [Borzecki, Ann M.] Bedford VAMC, Bedford, MA USA. [Cevasco, Marisa; Itani, Kamal M. F.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Chen, Q (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res COLMR, 150 S Huntington Ave, Boston, MA 02130 USA. EM qc2112@bu.edu FU Department of Veterans Affairs Health Services Research and Development Service [SDR 07-002] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Department of Veterans Affairs Health Services Research and Development Service (Grant Number SDR 07-002). NR 40 TC 2 Z9 2 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAY-JUN PY 2013 VL 28 IS 3 BP 206 EP 213 DI 10.1177/1062860612459070 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 136QY UT WOS:000318379700003 PM 23007377 ER PT J AU Hosokawa, S Koseki, H Nagashima, M Maeyama, Y Yomogida, K Mehr, C Rutledge, M Greenfeld, H Kaneki, M Tompkins, RG Martyn, JAJ Yasuhara, SE AF Hosokawa, Sachiko Koseki, Hiroaki Nagashima, Michio Maeyama, Yoshihiro Yomogida, Kentaro Mehr, Chelsea Rutledge, Madeleine Greenfeld, Hannah Kaneki, Masao Tompkins, Ronald G. Martyn, J. A. Jeevendra Yasuhara, Shingo E. TI Title efficacy of phosphodiesterase 5 inhibitor on distant burn-induced muscle autophagy, microcirculation, and survival rate SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE muscle wasting; burn injury; phosphodiesterase 5 inhibitor; sildenafil; tadalafil; vardenafil; autophagy; skeletal muscle; in vivo microscopy; Atg8/LC3; autophagosome turnover and maturation ID NITRIC-OXIDE; MUSCULAR-DYSTROPHY; OXIDATIVE STRESS; RELAXING FACTOR; INJURY; SILDENAFIL; APOPTOSIS; PROTEIN; MICROSCOPY; LC3 AB Skeletal muscle wasting is an exacerbating factor in the prognosis of critically ill patients. Using a systemic burn injury model in mice, we have established a role of autophagy in the resulting muscle wasting that is distant from the burn trauma. We provide evidence that burn injury increases the autophagy turnover in the distal skeletal muscle by conventional postmortem tissue analyses and by a novel in vivo microscopic method using an autophagy reporter gene (tandem fluorescent LC3). The effect of tadalafil, a phosphodiesterase 5 inhibitor (PDE5I), on burn-induced skeletal muscle autophagy is documented and extends our published results that PDE5Is attenuates muscle degeneration in a muscular dystrophy model. We also designed a translational experiment to examine the impact of PDE5I on whole body and demonstrated that PDE5I administration lessened muscle atrophy, mitigated microcirculatory disturbance, and improved the survival rate after burn injury. C1 [Hosokawa, Sachiko; Koseki, Hiroaki; Nagashima, Michio; Maeyama, Yoshihiro; Yomogida, Kentaro; Mehr, Chelsea; Rutledge, Madeleine; Greenfeld, Hannah; Kaneki, Masao; Tompkins, Ronald G.; Martyn, J. A. Jeevendra; Yasuhara, Shingo E.] Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesiol & Crit Care & Pain Med, Boston, MA 02114 USA. [Hosokawa, Sachiko; Koseki, Hiroaki; Nagashima, Michio; Maeyama, Yoshihiro; Yomogida, Kentaro; Mehr, Chelsea; Rutledge, Madeleine; Greenfeld, Hannah; Kaneki, Masao; Tompkins, Ronald G.; Martyn, J. A. Jeevendra; Yasuhara, Shingo E.] Harvard Univ, Sch Med, Boston, MA USA. RP Yasuhara, SE (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM shingo_yasuhara@yahoo.com OI Nagashima, Michio/0000-0001-7416-5367 FU Shriners Research grant FX This work is supported by a Shriners Research grant. NR 52 TC 13 Z9 13 U1 0 U2 3 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 MAY PY 2013 VL 304 IS 9 BP E922 EP E933 DI 10.1152/ajpendo.00078.2013 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 137ZA UT WOS:000318476000002 PM 23512808 ER PT J AU Steenkamp, MM Nash, WP Litz, BT AF Steenkamp, Maria M. Nash, William P. Litz, Brett T. TI Post-Traumatic Stress Disorder Review of the Comprehensive Soldier Fitness Program SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID UK ARMED-FORCES; MENTAL-HEALTH; SYMPTOMS; INTERVENTION; ADOLESCENTS; AFGHANISTAN; PSYCHOLOGY; SCIENCE; TRAUMA; FUTURE AB Since the start of the wars in Afghanistan and Iraq, the U.S. military has implemented several population-based initiatives to enhance psychological resilience and prevent psychological morbidity in troops. The largest of these initiatives is the Army's Comprehensive Soldier Fitness (CSF) program, which has been disseminated to more than 1 million soldiers. However, to date, CSF has not been independently and objectively reviewed, and the degree to which it successfully promotes adaptive outcomes and prevents the development of deployment-related mental health disorders such as post-traumatic stress disorder (PTSD) is uncertain. This paper critically evaluates the theoretic foundation for and evidence supporting the use of CSF. (Am J Prev Med 2013;44(5):507-512) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Steenkamp, Maria M.; Litz, Brett T.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Steenkamp, Maria M.; Litz, Brett T.] Boston Univ, Sch Med, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02118 USA. [Litz, Brett T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Nash, William P.] Boston VA Res Inst, Boston, MA USA. RP Steenkamp, MM (reprint author), Boston Vet Affairs Med Ctr, 150 South Huntington Ave 13B-73, Boston, MA 02130 USA. EM maria.steenkamp2@va.gov NR 35 TC 14 Z9 16 U1 2 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2013 VL 44 IS 5 BP 507 EP 512 DI 10.1016/j.amepre.2013.01.013 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 128XS UT WOS:000317803600012 PM 23597815 ER PT J AU Greenwood, TA Swerdlow, NR Gur, RE Cadenhead, KS Calkins, ME Dobie, DJ Freedman, R Green, MF Gur, RC Lazzeroni, LC Nuechterlein, KH Olincy, A Radant, AD Ray, A Schork, NJ Seidman, LJ Siever, LJ Silverman, JM Stone, WS Sugar, CA Tsuang, DW Tsuang, MT Turetsky, BI Light, GA Braff, DL AF Greenwood, Tiffany A. Swerdlow, Neal R. Gur, Raquel E. Cadenhead, Kristin S. Calkins, Monica E. Dobie, Dorcas J. Freedman, Robert Green, Michael F. Gur, Ruben C. Lazzeroni, Laura C. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Ray, Amrita Schork, Nicholas J. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Sugar, Catherine A. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Light, Gregory A. Braff, David L. TI Genome-Wide Linkage Analyses of 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUSCEPTIBILITY LOCUS; PREPULSE INHIBITION; CANDIDATE GENES; WORKING-MEMORY; FOLLOW-UP; ANTISACCADE PERFORMANCE; CHROMOSOME-15 LOCUS; POTENTIAL LINKAGE; COMPLEX DISEASES; ASSOCIATION AB Objective: The Consortium on the Genetics of Schizophrenia has undertaken a large multisite study to characterize 12 neurophysiological and neurocognitive endophenotypic measures as a step toward understanding the complex genetic basis of schizophrenia. The authors previously demonstrated the heritability of these endophenotypes; in the present study, genetic linkage was evaluated. Method: Each family consisted of a proband with schizophrenia, at least one unaffected sibling, and both parents. A total of 1,286 participants from 296 families were genotyped in two phases, and 1,004 individuals were also assessed for the endophenotypes. Linkage analyses of the 6,055 single-nucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigree-wide regression methods. Results: Linkage analyses of the 12 endophenotypes collectively identified one region meeting genome-wide significance criteria, with a LOD (log of odds) score of 4.0 on chromosome 3p14 for the antisaccade task, and another region on 1p36 nearly meeting genome-wide significance, with a LOD score of 3.5. for emotion recognition. Chromosomal regions meeting genome-wide suggestive criteria with LOD scores >2.2 were identified for spatial processing (2p25 and 16q23), sensorimotor dexterity (2q24 and 2q32), prepulse inhibition (5p15), the California Verbal. Learning Test (8q24), the degraded-stimulus Continuous Performance Test (10q26), face memory (10q26 and 12p12), and the Letter-Number Span (14q23). Conclusions: Twelve regions meeting genome-wide significant and suggestive criteria for previously identified heritable, schizophrenia-related endophenotypes were observed, and several genes of potential neurobiological interest were identified. Replication and further genomic Studies are needed to assess the biological significance of these results. (Am J Psychiatry 2013; 170:521-532) C1 [Greenwood, Tiffany A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Colorado Denver, Dept Psychiat, Aurora, CO USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Scripps Translat Sci Inst, La Jolla, CA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. James J Peters VA Med Ctr, New York, NY USA. Univ Calif Los Angeles, Dept Biostat, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. VA San Diego Healthcare Syst, VISN 22, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. RP Greenwood, TA (reprint author), Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. EM tgreenwood@ucsd.edu; dbraff@ucsd.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016; OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920 FU Brain Plasticity; Genentech; Janssen Scientific Affairs; Lundbeck Pharmaceuticals; AstraZeneca; Pfizer; Bristol-Myers Squibb; Hoffman-La Roche; NIMH [R01-MH-065588, R01-MH-065562, R01-MH-065707, R01-MH-065554, R01-MH-065578, R01-MH-065558, R01-MH-86135, K01-MH-087889]; NIH [HNSN268200782096C] FX Dr. Swerdlow has served as a consultant to Neurocrine. Dr. Green has served as a consultant to Abbott Laboratories, Amgen, Biogen, Mnemosyne, Roche, and Shire. Dr. Nuechterlein has received research grant support from Brain Plasticity, Genentech, and Janssen Scientific Affairs and has served as a consultant to Genentech and Otsuka. Dr. Olincy has received research grant support from Lundbeck Pharmaceuticals. Dr. Turetsky has received research grant support from AstraZeneca and Pfizer and consulting fees from Bristol-Myers Squibb and Hoffman-La Roche. Dr. Light has participated in a scientific advisory board meeting for Astellas. All other authors report no financial relationships with commercial interests.; Supported by NIMH grants R01-MH-065588, R01-MH-065562, R01-MH-065707, R01-MH-065554, R01-MH-065578, R01-MH-065558, R01-MH-86135, and K01-MH-087889. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from NIH to Johns Hopkins University (contract number HNSN268200782096C). NR 93 TC 54 Z9 55 U1 3 U2 24 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 MAY PY 2013 VL 170 IS 5 BP 521 EP 532 DI 10.1176/appi.ajp.2012.12020186 PG 12 WC Psychiatry SC Psychiatry GA 135XO UT WOS:000318324200013 PM 23511790 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. CA Bipolar Trials Network TI In Whom Does Lithium Work? Response SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter ID BIPOLAR DISORDER; MAINTENANCE TREATMENT; TRIAL C1 [Nierenberg, Andrew A.; Bipolar Trials Network] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 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 MAY PY 2013 VL 170 IS 5 BP 559 EP 560 DI 10.1176/appi.ajp.2013.13010038r PG 2 WC Psychiatry SC Psychiatry GA 135XO UT WOS:000318324200020 PM 23632847 ER PT J AU Jentes, ES Han, P Gershman, MD Rao, SR LaRocque, RC Staples, JE Ryan, ET AF Jentes, Emily S. Han, Pauline Gershman, Mark D. Rao, Sowmya R. LaRocque, Regina C. Staples, J. Erin Ryan, Edward T. CA Global TravEpiNet Consortium TI Travel Characteristics and Yellow Fever Vaccine Usage Among US Global TravEpiNet Travelers Visiting Countries with Risk of Yellow Fever Virus Transmission, 2009-2011 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INTERNATIONAL-AIRPORT; RELATIVES ABROAD; FRIENDS; RECOMMENDATIONS; PREVENTION; IMMIGRANTS; KNOWLEDGE; ATTITUDES; DISEASES AB Yellow fever (YF) vaccine-associated serious adverse events and changing YF epidemiology have challenged healthcare providers to vaccinate only travelers whose risk of YF during travel is greater than their risk of adverse events. We describe the travel characteristics and YF vaccine use among US travelers visiting Global TravEpiNet clinics from January of 2009 to March of 2011. Of 16,660 travelers, 5,588 (34%) had itineraries to areas with risk of YF virus transmission. Of those travelers visiting one country with YF risk (N = 4,517), 71% were vaccinated at the visit, and 20% were presumed to be immune from prior vaccination. However, travelers visiting friends and relatives (odds ratio [OR] = 2.57,95% confidence interval [95% CI] = 1.27-5.22) or going to Nigeria (OR = 3.01,95% CI = 1.37-6.62) were significantly more likely to decline vaccination. To optimize YF vaccine use, clinicians should discuss an individual's risk benefit assessment of vaccination and close knowledge gaps regarding vaccine use among at-risk populations. C1 [Jentes, Emily S.; Han, Pauline; Gershman, Mark D.] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA 30333 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Bedford Vet Adm Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Ft Collins, CO USA. [LaRocque, Regina C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Staples, J. Erin] Ctr Dis Control & Prevent, Arboviral Dis Branch, Div Vector Borne Dis, Ft Collins, CO USA. RP Jentes, ES (reprint author), Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, 1600 Clifton Rd,MS E-03, Atlanta, GA 30333 USA. EM ejentes@cdc.gov; hfd7@cdc.gov; dvj8@cdc.gov; sowmya.rao@va.gov; rclarocque@partners.org; auv1@cdc.gov; etryan@partners.org FU US Centers for Disease Control and Prevention [U19CI000514, U01CK000175] FX This work was supported by Grants U19CI000514 and U01CK000175 from the US Centers for Disease Control and Prevention. NR 29 TC 2 Z9 2 U1 0 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2013 VL 88 IS 5 BP 954 EP 961 DI 10.4269/ajtmh.12-0463 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 136WR UT WOS:000318394600025 PM 23458961 ER PT J AU Gros, DF Milanak, ME Brady, KT Back, SE AF Gros, Daniel F. Milanak, Melissa E. Brady, Kathleen T. Back, Sudie E. TI Frequency and Severity of Comorbid Mood and Anxiety Disorders in Prescription Opioid Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SUBSTANCE USE DISORDERS; PTSD; ABUSERS; INDEX AB Background and Objectives: Comorbid substance use disorders and mood and anxiety disorders are associated with more severe psychiatric symptoms, social and occupational impairment, and economic burden. To date, the majority of research has focused on comorbidity in illicit drug users, rather than prescription drug users. To address this gap in the literature, the present cross-sectional study investigated the clinical profiles of individuals with prescription opioid dependence with or without comorbid mood and anxiety disorders. Methods: Ninety individuals with prescription opioid use were recruited to participate in the study procedures. All participants completed a structured clinical interview and series of self-report measures. Results and Conclusions: Of the 85 individuals with prescription opioid dependence, 47.1% (n = 40) were diagnosed with a comorbid mood or anxiety disorder. The findings showed that individuals with prescription opioid dependence and comorbid mood and anxiety disorders demonstrated significantly more severe alcohol use, psychiatric symptoms, and sleep impairment than individuals without comorbidity. Scientific Significance: The findings highlight the frequency and severity of co-occurring mood and anxiety disorders in individuals with prescription opioid dependence and suggest that integrated interventions are needed to address these growing problems. C1 [Gros, Daniel F.; Brady, Kathleen T.; Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Gros, Daniel F.; Milanak, Melissa E.; Brady, Kathleen T.; Back, Sudie E.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU NIDA NIH HHS [K23 DA021228, K24 DA00435] NR 22 TC 8 Z9 8 U1 4 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2013 VL 22 IS 3 BP 261 EP 265 DI 10.1111/j.1521-0391.2012.12008.x PG 5 WC Substance Abuse SC Substance Abuse GA 134RO UT WOS:000318232200013 PM 23617869 ER PT J AU Chakravorty, S Grandner, MA Kranzler, HR Mavandadi, S Kling, MA Perlis, ML Oslin, DW AF Chakravorty, Subhajit Grandner, Michael A. Kranzler, Henry R. Mavandadi, Shahrzad Kling, Mitchel A. Perlis, Michael L. Oslin, David W. TI Insomnia in Alcohol Dependence: Predictors of Symptoms in a Sample of Veterans Referred from Primary Care SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; DRUG-USE DISORDERS; SLEEP DISTURBANCES; SUICIDAL IDEATION; UNITED-STATES; DSM-IV; COOCCURRENCE; COMORBIDITY; POPULATION; PREVALENCE AB Objective: Patients with alcohol dependence presenting for treatment may have multiple associated co-morbid conditions and limited social supports, which complicate treatment. Each of these factors has been independently associated with complaints of insomnia. In this preliminary study, we investigated the relations between insomnia complaints and socio-demographic factors and psychiatric comorbidity in treatment-seeking patients with alcohol dependence. Method: We conducted a retrospective chart review on 84 consecutive patients referred to the Behavioral Health Laboratory of the Philadelphia Veterans Affairs Medical Center for evaluation of psychiatric and substance use disorders. Patients met DSM-IV diagnostic criteria for alcohol dependence and completed a series of self-assessments of sleep. Univariate and multivariable analyses were used to examine the relations amongst the variables of interest. Results: In multivariable models, Sleep Latency was significantly greater in individuals without partners (p = .01), those with psychiatric disorders (p = .03) and smokers (p = .01), with a nonsignificant trend for those with past-year suicidal ideation. No significant predictor of Wake Time After Sleep Onset was seen. Poor Sleep Quality was predicted by younger age (OR = .93 [.88, .98], p = .004) and the presence of a psychiatric disorder (OR = 20.80 [4, 102], p = .0002), with a non-significant trend for suicidal ideation. Conclusions: Insomnia symptoms in treatment-seeking alcohol dependent patients should prompt consideration of the individuals' psychiatric and psychosocial features. C1 [Chakravorty, Subhajit; Kranzler, Henry R.; Mavandadi, Shahrzad; Kling, Mitchel A.; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, MIRECC VISN 4, Philadelphia, PA 19104 USA. [Chakravorty, Subhajit; Grandner, Michael A.; Kranzler, Henry R.; Mavandadi, Shahrzad; Kling, Mitchel A.; Perlis, Michael L.; Oslin, David W.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Chakravorty, S (reprint author), Philadelphia Vet Affairs Med Ctr, MIRECC, 2nd Floor,Postal Code 116,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM subhajit.chakravorty@uphs.upenn.edu OI Kling, Mitchel/0000-0002-2232-1409 FU NHLBI NIH HHS [T32 HL007713, 5T32HL007713, K23 HL110216]; NIEHS NIH HHS [R21 ES022931] NR 31 TC 8 Z9 8 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2013 VL 22 IS 3 BP 266 EP 270 DI 10.1111/j.1521-0391.2012.12009.x PG 5 WC Substance Abuse SC Substance Abuse GA 134RO UT WOS:000318232200014 PM 23617870 ER PT J AU Wilens, TE AF Wilens, Timothy E. TI Family History of Substance Use Disorders (SUD) and Offspring SUD: Results from a Controlled Family Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy E.] 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2013 VL 22 IS 3 BP 308 EP 308 PG 1 WC Substance Abuse SC Substance Abuse GA 134RO UT WOS:000318232200033 ER PT J AU Ward, N Harvey, M Czarnecki, K AF Ward, Nalan Harvey, Margaret Czarnecki, Kristen TI Innovations in Substance Abuse Care Delivery: Does "Orientation Group" Before Intake Increase Clinician Productivity? SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Ward, Nalan; Harvey, Margaret; Czarnecki, Kristen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ward, Nalan; Harvey, Margaret] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2013 VL 22 IS 3 BP 311 EP 311 PG 1 WC Substance Abuse SC Substance Abuse GA 134RO UT WOS:000318232200040 ER PT J AU Ross, R Stoeckel, L Krashes, M Connery, H AF Ross, Rachel Stoeckel, Luke Krashes, Michael Connery, Hilary TI Drugs at the Dinner Table: Emerging Interface in the Science of Addiction and Appetitive Behavior SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Ross, Rachel] MGH McLean Adult Psychiat Residency Training Prog, Mclean, VA USA. [Stoeckel, Luke] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ross, Rachel; Krashes, Michael] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Connery, Hilary] McLean Hosp, Alcohol & Drug Abuse Treatment Program, Mclean, VA USA. [Ross, Rachel; Stoeckel, Luke; Krashes, Michael; Connery, Hilary] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2013 VL 22 IS 3 BP 312 EP 312 PG 1 WC Substance Abuse SC Substance Abuse GA 134RO UT WOS:000318232200044 ER PT J AU Wilens, TE AF Wilens, Timothy E. TI Substance Use in Young Adults with Bipolar Disorder: 5-Year Findings of an Ongoing Longitudinal Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2013 VL 22 IS 3 BP 320 EP 320 PG 1 WC Substance Abuse SC Substance Abuse GA 134RO UT WOS:000318232200067 ER PT J AU Ward, N Margaret, H AF Ward, Nalan Margaret, Harvey TI How to Increase Access to Substance Abuse Treatment: Implementing NIATx Model SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Ward, Nalan; Margaret, Harvey] 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 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2013 VL 22 IS 3 BP 321 EP 321 PG 1 WC Substance Abuse SC Substance Abuse GA 134RO UT WOS:000318232200069 ER PT J AU Iftimia, N Ferguson, RD Mujat, M Patel, AH Zhang, EZ Fox, W Rajadhyaksha, M AF Iftimia, Nicusor Ferguson, R. Daniel Mujat, Mircea Patel, Ankit H. Zhang, Ellen Ziyi Fox, William Rajadhyaksha, Milind TI Combined reflectance confocal microscopy/optical coherence tomography imaging for skin burn assessment SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID LASER-DOPPLER FLOWMETRY; OPTICAL COHERENCE; MULTIPHOTON MICROSCOPY; WOUND INFECTIONS; DEPTH; DIAGNOSIS; MICROCIRCULATION; MICROANGIOGRAPHY AB A combined high-resolution reflectance confocal microscopy (RCM)/optical coherence tomography (OCT) instrument for assessing skin burn gravity has been built and tested. This instruments allows for visualizing skin intracellular details with submicron resolution in the RCM mode and morphological and birefringence modifications to depths on the order of 1.2 mm in the OCT mode. Preliminary testing of the dual modality imaging approach has been performed on the skin of volunteers with some burn scars and on normal and thermally-injured Epiderm FTTM skin constructs. The initial results show that these two optical technologies have complementary capabilities that can offer the clinician a set of clinically comprehensive parameters: OCT helps to visualize deeper burn injuries and possibly quantify collagen destruction by measuring skin birefringence, while RCM provides submicron details of the integrity of the epidermal layer and identifies the presence of the superficial blood flow in the upper dermis. Therefore, the combination of these two technologies within the same instrument may provide a more comprehensive set of parameters that may help clinicians to more objectively and nonivasively assess burn injury gravity by determining tissue structural integrity and viability. (C) 2013 Optical Society of America C1 [Iftimia, Nicusor; Ferguson, R. Daniel; Mujat, Mircea; Patel, Ankit H.] Phys Sci Inc, Andover, MA 01810 USA. [Zhang, Ellen Ziyi] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Fox, William] Lucid Inc, Rochester, NY 14604 USA. [Rajadhyaksha, Milind] Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10021 USA. RP Iftimia, N (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM iftimia@psicorp.com FU Department of Defense [W81XWH-11-C-0486]; NCI [1R43CA162561-01A1]; Center for Biomedical OCT Research and Translation [P41EB015903]; National Center for Research Resources; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health FX The work of the authors was supported by the Department of Defense through Grant Number W81XWH-11-C-0486 and partially through NCI Grant Number 1R43CA162561-01A1.; Ellen Ziyi Zhang was supported by the Center for Biomedical OCT Research and Translation through Grant Number P41EB015903, awarded by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. NR 45 TC 14 Z9 14 U1 2 U2 30 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 MAY 1 PY 2013 VL 4 IS 5 BP 680 EP 695 DI 10.1364/BOE.4.000680 PG 16 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 137FR UT WOS:000318421400004 PM 23667785 ER PT J AU Pagel, T Baldessarini, RJ Franklin, J Baethge, C AF Pagel, Tobias Baldessarini, Ross J. Franklin, Jeremy Baethge, Christopher TI Characteristics of patients diagnosed with schizoaffective disorder compared with schizophrenia and bipolar disorder SO BIPOLAR DISORDERS LA English DT Review DE bipolar; meta-analysis; schizoaffective; schizophrenia ID PSYCHOTIC MOOD DISORDERS; TERM-FOLLOW-UP; PSYCHIATRIC-DISORDERS; CLINICAL-FEATURES; NEGATIVE SYMPTOMS; THOUGHT-DISORDER; RISK-FACTOR; PREVALENCE; POPULATION; CLOZAPINE AB Objectives Information on basic demographic and clinical characteristics of schizoaffective disorder is sparse and subject to sampling bias and low diagnostic reliability. In the present study we aimed to: (i) estimate the demographic and clinical descriptors in schizoaffective disorder patients and (ii) compare the findings with those with schizophrenia and bipolar disorder. Methods To minimize sampling bias and low reliability, we systematically reviewed studies that simultaneously compared schizoaffective, schizophrenia, and bipolar disorder patients. We estimated demographic, clinical, and psychometric characteristics based on weighted pooling, and compared disorders by meta-analysis. We also estimated whether schizoaffective disorder is closer to schizophrenia or to bipolar disorder. Results We identified 50 studies that included 18312 patients. Most characteristics of the 2684 schizoaffective disorder patients fell between those of 4814 diagnosed with bipolar disorder and 10814 with schizophrenia. However, the schizoaffective group had the highest proportion of women (52%), had the youngest age at illness onset (23.3 +/- 3.8years), and had the highest standardized ratings of psychosis and depression. Differences in pooled parameters between schizoaffective versus schizophrenia and versus bipolar disorder subjects were similar. Values for patients with schizoaffective disorders mostly were intermediate between schizophrenia and bipolar disorder. However, the majority of studies showed schizoaffective patients to be more like schizophrenia than bipolar disorder patients in seven out of nine demographic and clinical categories as well as in five out of eight psychometric measures. These results remained similar when we restricted the analyses to studies with psychotic bipolar disorder patients only or to studies using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IIIR and DSM-IV only. Conclusions The present study provided estimates of important characteristics of schizoaffective disorder as balanced as possible in summarizing the findings from observational studies as unbiased as possible. The results did not support the hypothesis that schizoaffective disorder is primarily an affective disorder. The stronger resemblance of schizoaffective disorder to schizophrenia than to bipolar disorder needs further investigation. C1 [Pagel, Tobias; Baethge, Christopher] Univ Cologne, Sch Med, Dept Psychiat & Psychotherapy, D-50937 Cologne, Germany. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.; Baethge, Christopher] Massachusetts Gen Hosp, Int Consortium Psychot & Bipolar Disorders Res, McLean Div, Boston, MA 02114 USA. [Franklin, Jeremy] Univ Cologne, Sch Med, Inst Med Stat Informat & Epidemiol, D-50937 Cologne, Germany. RP Baethge, C (reprint author), Univ Cologne, Klin Psychiat & Psychotherapie, Kerpener Str 62, D-50937 Cologne, Germany. EM cbaethge@uni-koeln.de FU Bruce J. Anderson Foundation; McLean Private Donors Psychiatric Research Fund FX We gratefully acknowledge the assistance of Dr. Elie Cheniaux of the Institute of Psychiatry, Federal University (Rio de Janeiro, Brazil) in providing bibliographic references from her review of schizoaffective disorder. This report is a component of the doctoral dissertation of Tobias Pagel. The work was supported, in part, by a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Psychiatric Research Fund (RJB). NR 78 TC 20 Z9 20 U1 3 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2013 VL 15 IS 3 BP 229 EP 239 DI 10.1111/bdi.12057 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 136OV UT WOS:000318372100001 PM 23528024 ER PT J AU Holloway, CL DeLaney, TF Alektiar, KM Devlin, PM O'Farrell, DA Demanes, DJ AF Holloway, Caroline L. DeLaney, Thomas F. Alektiar, Kaled M. Devlin, Phillip M. O'Farrell, Desmond A. Demanes, D. Jeffrey TI American Brachytherapy Society (ABS) consensus statement for sarcoma brachytherapy SO BRACHYTHERAPY LA English DT Article DE Sarcoma; Brachytherapy; Consensus statement ID SOFT-TISSUE SARCOMA; HIGH-DOSE-RATE; EXTERNAL-BEAM RADIOTHERAPY; LIMB-SPARING SURGERY; PERIOPERATIVE INTERSTITIAL BRACHYTHERAPY; INTRAOPERATIVE RADIATION-THERAPY; ADJUVANT RADIATION; PROGNOSTIC-FACTORS; PULMONARY METASTASECTOMY; RETROPERITONEAL SARCOMA AB PURPOSE: To present recommendations for the use of brachytherapy (BT) in patients with soft tissue sarcoma (STS). METHODS: A group of practitioners with expertise and experience in sarcoma BT formulated recommendations for BT in STS based on clinical experience and literature review. RESULTS: The indications for adjuvant BT are discussed. There is no consensus on the use of BT alone or in combination with external beam radiation therapy (EBRT), but factors that influence the selection of this modality include tumor grade and size, prior surgeries, and tumor recurrence. Low-dose-rate, high-dose-rate, and pulsed-dose-rate radiation are all acceptable BT modalities to use for STS. Recommendations are made for patient selection, techniques, dose rates, and dosages. Outcome data and toxicity data are reviewed. CONCLUSIONS: BT is a useful component of the treatment of STS. The advantages of BT are the targeted dose distribution, low integral dose, and short treatment times. Ultimately the clinician should select the modality or combination of modalities that are most familiar to the treatment team and suitable to the patient. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Holloway, Caroline L.] BC Canc Agcy, Vancouver Isl Ctr, Dept Radiat Oncol, Victoria, BC V8R 6V5, Canada. [DeLaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Alektiar, Kaled M.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Devlin, Phillip M.; O'Farrell, Desmond A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Canc Ctr, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Radiat Oncol, Div Brachytherapy, Los Angeles, CA 90024 USA. RP Holloway, CL (reprint author), BC Canc Agcy, Vancouver Isl Ctr, Dept Radiat Oncol, 2410 Lee Ave, Victoria, BC V8R 6V5, Canada. EM cholloway@bccancer.bc.ca NR 87 TC 15 Z9 15 U1 0 U2 3 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 MAY-JUN PY 2013 VL 12 IS 3 BP 179 EP 190 DI 10.1016/j.brachy.2012.12.002 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 136BG UT WOS:000318333800001 PM 23434220 ER PT J AU Viswanathan, AN Szymonifka, J Tempany-Afdhal, CM O'Farrell, DA Cormack, RA AF Viswanathan, Akila N. Szymonifka, Jackie Tempany-Afdhal, Clare M. O'Farrell, Desmond A. Cormack, Robert A. TI A prospective trial of real-time magnetic resonance-guided catheter placement in interstitial gynecologic brachytherapy SO BRACHYTHERAPY LA English DT Article DE Interstitial brachytherapy; Gynecologic malignancies; Toxicity ID CERVIX CANCER BRACHYTHERAPY; DOSE-VOLUME PARAMETERS; INTRACAVITARY BRACHYTHERAPY; VAGINAL-CANCER; CARCINOMA; OPTIMIZATION; RADIATION; RECOMMENDATIONS; IMPLANTATION; RECURRENCE AB PURPOSE: To present outcome and toxicity results of the first real-time intraoperative MRI-guided interstitial approach to gynecologic cancer. METHODS AND MATERIALS: From February 2004 to December 2006, 25 patients with gynecologic malignancies were enrolled and treated in a prospective clinical trial of real-time MRI-guided interstitial brachytherapy. This was followed by a confirmatory CT imaging scan. Statistical analyses included Kaplan-Meier estimates for overall and relapse-free survival. RESULTS: MRI visualization of needles during placement permitted accurate placement with no inadvertent insertions. This prevented unnecessary normal-tissue perforation as confirmed by CT simulation. With a mean followup of 3.8 years (range, 2-6.8), 1-, 2-, and 3-year overall survival rates were 80%, 60% and 43%, respectively; corresponding relapse-free survival rates were 79%, 65%, and 59%, respectively. Actuarial acute toxicity rates for any grade were 0% at 0-14 days and 80% (all grade 1) at 14-90 days. Long-term (>180 days) actuarial toxicity rates were 8% gastrointestinal, 4% bladder and 4% vaginal. CONCLUSIONS: Real-time MRI guidance during insertion of interstitial needles followed by 3D-planning maximized opportunities for tumor targeting and sparing of normal tissues. Although image guidance requires additional anesthesia time, clinical outcomes indicate potential for a successful reduction in toxicity using 3D image-guided in addition to 3D image-planned brachytherapy. (C) 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Viswanathan, Akila N.; O'Farrell, Desmond A.; Cormack, Robert A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Szymonifka, Jackie] Massachusetts Gen Hosp, Dept Biostat Sci, Boston, MA 02114 USA. [Tempany-Afdhal, Clare M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 FU Friends of Dana-Farber Cancer Institute FX Dr. Viswanathan received support from a Friends of Dana-Farber Cancer Institute Award for this protocol. There are no current external funding sources for this study. NR 22 TC 30 Z9 30 U1 2 U2 8 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 MAY-JUN PY 2013 VL 12 IS 3 BP 240 EP 247 DI 10.1016/j.brachy.2012.08.006 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 136BG UT WOS:000318333800012 PM 23415048 ER PT J AU Sampaio, A Bouix, S Sousa, N Vasconcelos, C Fernandez, M Shenton, ME Goncalves, OF AF Sampaio, Adriana Bouix, Sylvain Sousa, Nuno Vasconcelos, Cristiana Fernandez, Montse Shenton, Martha E. Goncalves, Oscar F. TI Morphometry of corpus callosum in Williams syndrome: shape as an index of neural development SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Corpus callosum; MRI; Neurodevelopment; Williams syndrome ID HUMAN CEREBRAL-CORTEX; WHITE-MATTER; BRAIN-DEVELOPMENT; LONGITUDINAL MRI; ADOLESCENCE; CHILDHOOD; THICKNESS; CHILDREN; ABNORMALITIES; CONNECTIVITY AB Brain abnormalities in Williams syndrome (WS) have been consistently reported, despite few studies have devoted attention to connectivity between different brain regions in WS. In this study, we evaluated corpus callosum (CC) morphometry: bending angle, length, thickness and curvature of CC using a new shape analysis method in a group of 17 individuals with WS matched with a typically developing group. We used this multimethod approach because we hypothesized that neurodevelopmental abnormalities might result in both volume changes and structure deformation. Overall, we found reduced absolute CC cross-sectional area and volume in WS (mean CC and subsections). In parallel, we observed group differences regarding CC shape and thickness. Specifically, CC of WS is morphologically different, characterized by a larger bending angle and being more curved in the posterior part. Moreover, although CC in WS is shorter, a larger relative thickness of CC was found in all callosal sections. Finally, groups differed regarding the association between CC measures, age, white matter volume and cognitive performance. In conclusions, abnormal patterns of CC morphology and shape may be implicated in WS cognitive and behavioural phenotype. C1 [Sampaio, Adriana; Goncalves, Oscar F.] Univ Minho, Sch Psychol, Neuropsychophysiol Lab, CiPsi, Braga, Portugal. [Bouix, Sylvain; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Sousa, Nuno] Univ Minho, Life & Hlth Sci Res Inst, Braga, Portugal. [Vasconcelos, Cristiana] Hosp Santo Antonio, Dept Neuroradiol, Oporto, Portugal. [Fernandez, Montse] Univ Santiago de Compostela, Mol Genet Unit, Galician Publ Fdn Genom Med, Santiago De Compostela, Spain. [Shenton, Martha E.] VA Boston Healthcare Syst, Lab Neurosci, Clin Neurosci Div, Dept Psychiat, Brockton, MA USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. RP Sampaio, A (reprint author), Univ Minho, Sch Psychol, Neuropsychophysiol Lab, CiPsi, Braga, Portugal. EM adriana.sampaio@psi.uminho.pt; sylvain@bwh.harvard.edu RI Sousa, Nuno/C-2782-2009; Goncalves, Oscar/G-5278-2010; Sampaio, Adriana/C-8361-2011; OI Goncalves, Oscar/0000-0003-2735-9155; Sampaio, Adriana/0000-0001-7347-1282; Bouix, Sylvain/0000-0003-1326-6054; Sousa, Nuno/0000-0002-8755-5126 FU Fundacao para a Ciencia e Tecnologia (Portugal) [PIC/IC/83290/2007, PTDC/PSI-PCL/115316/2009]; National Institutes of Health [K05 MH070047] FX This research was supported by the grants PIC/IC/83290/2007 and PTDC/PSI-PCL/115316/2009 from Fundacao para a Ciencia e Tecnologia (Portugal). This study was also supported, in part, by grants from the National Institutes of Health (K05 MH070047). NR 64 TC 3 Z9 3 U1 0 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD MAY PY 2013 VL 218 IS 3 BP 711 EP 720 DI 10.1007/s00429-012-0423-4 PG 10 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA 135TE UT WOS:000318310600007 PM 22648762 ER PT J AU Lucisano, MP Nelson, P Morse, L Battaglino, R Watanabe, PCA da Silva, RAB da Silva, LAB AF Lucisano, Marilia Pacifico Nelson-Filho, Paulo Morse, Leslie Battaglino, Ricardo Aranha Watanabe, Plauto Christopher Bezerra da Silva, Raquel Assed Bezerra da Silva, Lea Assed TI Radiodensitometric and DXA analyses for the measurement of bone mineral density after systemic alendronate therapy SO BRAZILIAN ORAL RESEARCH LA English DT Article DE Bone Density; Alendronate; Bone Remodeling ID X-RAY ABSORPTIOMETRY; QUANTITATIVE COMPUTED-TOMOGRAPHY; CLINICAL-EFFICACY; IN-VIVO; OSTEOPOROSIS; RATS; MICE; BISPHOSPHONATES; DEFICIENCY; MECHANISMS AB Precise techniques for the measurement of maxillary bone mineral density (BMD) are useful for the early diagnosis of systemic diseases. The aim of this study was to compare in vivo the efficacy of dual-energy x-ray absorptiometry (DXA) and radiographic densitometry for the measurement of BMD after systemic administration of sodium alendronate. Wistar rats were randomly allocated to a control group (n = 5), which received distilled water, and a sodium alendronate group (n = 8), which received two doses of chemically pure sodium alendronate (1 mg/kg) per week. After 8 weeks, the animals were euthanized, the tibias were removed, and the BMD of the proximal tibial metaphysis was analyzed radiographically and by DXA. The data were subjected to statistical analysis by the Kruskal-Wallis test at a significance level of 5%. Both of the techniques revealed that the alendronate-treated group had a significantly higher BMD (p < 0.05) than the control group after 8 weeks of treatment. Comparing the groups with and without alendronate therapy revealed increases of 14.9% and 29.6% in BMD, as detected radiographically and by DXA, respectively. In conclusion, both of the methods Were able to detect an increase in BMD of the proximal tibial metaphysis after alendronate therapy. C1 [Lucisano, Marilia Pacifico; Nelson-Filho, Paulo; Bezerra da Silva, Raquel Assed; Bezerra da Silva, Lea Assed] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Pediat Clin Prevent & Community Dent, BR-14049 Ribeirao Preto, SP, Brazil. [Morse, Leslie] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Battaglino, Ricardo] Forsyth Inst, Dept Skeletal Biol, Cambridge, MA USA. [Aranha Watanabe, Plauto Christopher] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Stomatol & Physiol, BR-14049 Ribeirao Preto, SP, Brazil. RP Nelson, P (reprint author), Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Pediat Clin Prevent & Community Dent, BR-14049 Ribeirao Preto, SP, Brazil. EM nelson@forp.usp.br RI watanabe, plauto/C-6881-2015; battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015; Silva, Lea/B-3953-2016; Nelson-Filho, Paulo/L-1272-2016; Bezerra da Silva, Raquel /M-8655-2016 OI watanabe, plauto/0000-0001-5524-1395; Morse, Leslie/0000-0002-7426-6341; Silva, Lea/0000-0001-7118-6859; Nelson-Filho, Paulo/0000-0001-8802-6480; Bezerra da Silva, Raquel /0000-0002-0230-1347 NR 28 TC 1 Z9 1 U1 0 U2 4 PU SOCIEDADE BRASILEIRA DE PESQUISA ODONTOLOGICA PI SAO PAULO PA CIDADE UNIV, AV PROF LINEU PRESTES, ARMANDO SALLE OLIVEIRA, AVENIDA LINEU PRESTES, 2227, CP 8216, SAO PAULO, SP 05508-900, BRAZIL SN 1806-8324 J9 BRAZ ORAL RES JI Braz. Oral Res. PD MAY-JUN PY 2013 VL 27 IS 3 BP 252 EP 257 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 139KX UT WOS:000318582700010 PM 23739782 ER PT J AU Armstrong, WB Taylor, TH Kennedy, AR Melrose, RJ Messadi, DV Gu, M Le, AD Perloff, M Civantos, F Goodwin, WJ Wirth, LJ Kerr, AR Meyskens, FL AF Armstrong, William B. Taylor, Thomas H. Kennedy, Ann R. Melrose, Raymond J. Messadi, Diana V. Gu, Mai Le, Anh D. Perloff, Marjorie Civantos, Francisco Goodwin, William Jarrard Wirth, Lori J. Kerr, Alexander Ross Meyskens, Frank L., Jr. TI Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID PROTEASE ACTIVITY; IN-VITRO; CANCER; C-ERBB-2; CHEMOPREVENTION; SERUM; SOY; LESIONS; RISK AB Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering "Green" chemoprevention. (C) 2013 AACR. C1 [Armstrong, William B.; Taylor, Thomas H.; Meyskens, Frank L., Jr.] UC Irvine, Chao Family Comprehens Canc Ctr, Philadelphia, PA USA. [Armstrong, William B.] UC Irvine, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA USA. [Taylor, Thomas H.] Univ Penn, Genet Epidemiol Res Inst, Philadelphia, PA 19104 USA. [Taylor, Thomas H.] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA. [Kennedy, Ann R.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Melrose, Raymond J.] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. [Messadi, Diana V.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Gu, Mai] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA. [Le, Anh D.] Univ Penn, Philadelphia, PA 19104 USA. [Perloff, Marjorie] NCI, Canc Prevent Div, Rockville, MD USA. [Civantos, Francisco; Goodwin, William Jarrard] Univ Miami, Dept Otolaryngol Head & Neck Surg, Miami, FL USA. [Wirth, Lori J.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kerr, Alexander Ross] NYU, Coll Dent, New York, NY USA. RP Meyskens, FL (reprint author), Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Bldg 56,Route 81,101 City Dr Canc Ctr, Orange, CA 92868 USA. EM flmeyske@uci.edu FU NIH [U01-CA72294, P30-CA 62203] FX This work is supported by the NIH (U01-CA72294, P30-CA 62203; to F.L. Meyskens). NR 28 TC 17 Z9 18 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2013 VL 6 IS 5 BP 410 EP 418 DI 10.1158/1940-6207.CAPR-13-0004 PG 9 WC Oncology SC Oncology GA 137ZE UT WOS:000318476600007 PM 23639862 ER PT J AU Ittmann, M Huang, J Radaelli, E Martin, P Signoretti, S Sullivan, R Simons, BW Ward, JM Robinson, BD Chu, GC Loda, M Thomas, G Borowsky, A Cardiff, RD AF Ittmann, Michael Huang, Jiaoti Radaelli, Enrico Martin, Philip Signoretti, Sabina Sullivan, Ruth Simons, Brian W. Ward, Jerrold M. Robinson, Brian D. Chu, Gerald C. Loda, Massimo Thomas, George Borowsky, Alexander Cardiff, Robert D. TI Animal Models of Human Prostate Cancer: The Consensus Report of the New York Meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee SO CANCER RESEARCH LA English DT Review ID GENETICALLY-ENGINEERED MICE; TO-MESENCHYMAL TRANSITION; INTRAEPITHELIAL NEOPLASIA; ANDROGEN RECEPTOR; REACTIVE STROMA; PTEN LOSS; XENOGRAFT MODELS; IN-VIVO; EXPRESSION; GROWTH AB Animal models, particularly mouse models, play a central role in the study of the etiology, prevention, and treatment of human prostate cancer. While tissue culture models are extremely useful in understanding the biology of prostate cancer, they cannot recapitulate the complex cellular interactions within the tumor microenvironment that play a key role in cancer initiation and progression. The National Cancer Institute (NCI) Mouse Models of Human Cancers Consortium convened a group of human and veterinary pathologists to review the current animal models of prostate cancer and make recommendations about the pathologic analysis of these models. More than 40 different models with 439 samples were reviewed, including genetically engineered mouse models, xenograft, rat, and canine models. Numerous relevant models have been developed over the past 15 years, and each approach has strengths and weaknesses. Analysis of multiple genetically engineered models has shown that reactive stroma formation is present in all the models developing invasive carcinomas. In addition, numerous models with multiple genetic alterations display aggressive phenotypes characterized by sarcomatoid carcinomas and metastases, which is presumably a histologic manifestation of epithelial-mesenchymal transition. The significant progress in development of improved models of prostate cancer has already accelerated our understanding of the complex biology of prostate cancer and promises to enhance development of new approaches to prevention, detection, and treatment of this common malignancy. (C) 2013 AACR. C1 [Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Ittmann, Michael] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Huang, Jiaoti] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Borowsky, Alexander; Cardiff, Robert D.] Univ Calif Davis, Dept Pathol & Lab Med, Davis, CA 95616 USA. [Borowsky, Alexander; Cardiff, Robert D.] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. [Martin, Philip] Ctr Adv Preclin Res, Frederick Natl Lab Canc Res, Frederick, MD USA. [Simons, Brian W.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. [Ward, Jerrold M.] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Bethesda, MD USA. [Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dept Pathol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Chu, Gerald C.; Loda, Massimo] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sullivan, Ruth] Univ Wisconsin, Madison Carbone Canc Ctr, Madison, WI USA. [Sullivan, Ruth] Res Anim Resources Ctr, Madison, WI USA. [Sullivan, Ruth] Lab Opt & Computat Instrumentat, Madison, WI USA. [Robinson, Brian D.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Thomas, George] Oregon Hlth & Sci Univ, Dept Pathol & Lab Med, Portland, OR 97201 USA. [Radaelli, Enrico] Univ Milan, Sch Vet Med, Dept Anim Pathol Hyg & Publ Hlth, Milan, Italy. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.edu RI Simons, Brian/G-7352-2015 OI Simons, Brian/0000-0003-0644-211X FU NCI: U01 Mouse Models of Human Cancers Consortium [U01CA141497, U01 CA141582]; UCLA, Pacific Northwest and DF/HCC SPOREs in Prostate Cancer [P01 CA89021, RO1 CA131945]; UWCCC Core Grant through the OHSU-Knight Cancer Institute [P30 CA014520, P30 CA069533 13S5]; Department of Defense Prostate Cancer Research Program [W81XWH-11-1-0227]; Prostate Cancer Foundation; [P30CA125123] FX This study was supported by NCI: U01 Mouse Models of Human Cancers Consortium (U01CA141497 and U01 CA141582); P30CA125123 (M. Ittmann); UCLA, Pacific Northwest and DF/HCC SPOREs in Prostate Cancer, P01 CA89021 (M. Loda) and RO1 CA131945 (M. Loda); UWCCC Core Grant P30 CA014520 (R. Sullivan) P30 CA069533 13S5 through the OHSU-Knight Cancer Institute (G. Thomas); Department of Defense Prostate Cancer Research Program (W81XWH-11-1-0227; J. Huang); and Prostate Cancer Foundation. NR 74 TC 64 Z9 68 U1 4 U2 27 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 MAY 1 PY 2013 VL 73 IS 9 BP 2718 EP 2736 DI 10.1158/0008-5472.CAN-12-4213 PG 19 WC Oncology SC Oncology GA 136KJ UT WOS:000318360500002 PM 23610450 ER PT J AU Crompton, BD Carlton, AL Thorner, AR Christie, AL Du, JY Calicchio, ML Rivera, MN Fleming, MD Kohl, NE Kung, AL Stegmaier, K AF Crompton, Brian D. Carlton, Anne L. Thorner, Aaron R. Christie, Amanda L. Du, Jinyan Calicchio, Monica L. Rivera, Miguel N. Fleming, Mark D. Kohl, Nancy E. Kung, Andrew L. Stegmaier, Kimberly TI High-Throughput Tyrosine Kinase Activity Profiling Identifies FAK as a Candidate Therapeutic Target in Ewing Sarcoma SO CANCER RESEARCH LA English DT Article ID FOCAL ADHESION KINASE; CELL-MIGRATION; STANDARD CHEMOTHERAPY; NEUROECTODERMAL TUMOR; GROWTH; RECEPTOR; INHIBITOR; CANCER; FAMILY; PATHWAY AB Limited progress has been made in the treatment of advanced-stage pediatric solid tumors despite the accelerated pace of cancer discovery over the last decade. Tyrosine kinase inhibition is one tractable therapeutic modality for treating human malignancy. However, little is known about the kinases critical to the development or maintenance of many pediatric solid tumors such as Ewing sarcoma. Using a fluorescent, bead-based technology to profile activated tyrosine kinases, we identified focal adhesion kinase (FAK, PTK2) as a candidate target in Ewing sarcoma. FAK is a tyrosine kinase critical for cellular adhesion, growth, and survival. As such, it is a compelling target for cancer-based therapy. In this study, we have shown that FAK is highly phosphorylated in primary Ewing sarcoma tumor samples and that downregulation of FAK by short hairpin RNA and treatment with a FAK-selective kinase inhibitor, PF-562271, impaired growth and colony formation in Ewing sarcoma cell lines. Moreover, treatment of Ewing sarcoma cell lines with PF-562271 induced apoptosis and led to downregulation of AKT/mTOR and CAS activity. Finally, we showed that small-molecule inhibition of FAK attenuated Ewing sarcoma tumor growth in vivo. With FAK inhibitors currently in early-phase clinical trials for adult malignancies, these findings may bear immediate relevance to patients with Ewing sarcoma. (C) 2013 AACR. C1 [Crompton, Brian D.; Carlton, Anne L.; Thorner, Aaron R.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Crompton, Brian D.; Carlton, Anne L.; Thorner, Aaron R.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Christie, Amanda L.; Kohl, Nancy E.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02215 USA. [Rivera, Miguel N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rivera, Miguel N.; Stegmaier, Kimberly] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. RP Stegmaier, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D630, Boston, MA 02215 USA. EM kimberly_stegmaier@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X; Carlton, Anne/0000-0002-5921-6004 FU Cookies for Kids' Cancer, Golf Fights Cancer, Brian MacIsaac Sarcoma Foundation; Hyundai Hope on Wheels, Bear Necessities Pediatric Cancer Foundation, Pedal for Pediatrics; Burroughs Wellcome Fund; Howard Hughes Medical Institute; Stand-Up-to-Cancer Innovative Research Grant, a program of the Entertainment Industry Foundation [SU2C-AACR-IRG0509] FX This work was supported by Cookies for Kids' Cancer, Golf Fights Cancer, Brian MacIsaac Sarcoma Foundation (K. Stegmaier); Hyundai Hope on Wheels, Bear Necessities Pediatric Cancer Foundation, Pedal for Pediatrics (B. D. Crompton); Aid for Cancer Research (A. R. Thorner); Burroughs Wellcome Fund (M.N. Rivera); and the Howard Hughes Medical Institute (K. Stegmaier and M.N. Rivera). K. Stegmaier is also supported by a Stand-Up-to-Cancer Innovative Research Grant, a program of the Entertainment Industry Foundation (SU2C-AACR-IRG0509). NR 49 TC 12 Z9 12 U1 0 U2 11 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 MAY 1 PY 2013 VL 73 IS 9 BP 2873 EP 2883 DI 10.1158/0008-5472.CAN-12-1944 PG 11 WC Oncology SC Oncology GA 136KJ UT WOS:000318360500016 PM 23536552 ER PT J AU Cuadrado-Tejedor, M Cabodevilla, JF Zamarbide, M Gomez-Isla, T Franco, R Perez-Mediavilla, A AF Cuadrado-Tejedor, Mar Felipe Cabodevilla, Jesus Zamarbide, Marta Gomez-Isla, Teresa Franco, Rafael Perez-Mediavilla, Alberto TI Age-Related Mitochondrial Alterations without Neuronal Loss in the Hippocampus of a Transgenic Model of Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; early changes; hippocampus; mitochondrial dysfunction; neuronal loss; neurodegeneration; proteome; transgenic mouse; Tg2576 ID MOUSE MODEL; AMYLOID DEPOSITION; SYNAPSE LOSS; DEFICITS; PROTEIN; MICE; STRESS; MEMORY AB The Tg2576 mouse, which carries the Swedish mutant form of human beta-amyloid precursor protein (hAPP(swe)), develops Alzheimer's Disease (AD)-like phenotype (synaptic pathology, cognitive impairment and beta amyloid -A beta-plaques.) in the absence of significant neuronal loss. We have analyzed the hippocampal proteome of Tg2576, focusing on changes at 7 months of age, when A beta levels begin to increase but cognitive symptoms are still not evident, and at 16 months, when most AD-like features are manifested. Proteins differentially expressed with respect to wild-type animals were grouped according to their biological function and assessed in the context of AD. Metabolic enzymes, propionyl-CoA carboxylase, which has not been previously related to AD, and glutamine synthetase, which is a key enzyme for ammonium removal, were among deregulated proteins. Mitochondria of young animals have to cope with the metabolic stress and elevated ATP demand caused by overexpression of hAPP(swe). Significantly, a large number of mitochondrial proteins (16, 28% of the total) were deregulated in young Tg2576 mice and seven of them were found at normal levels in aged animals. Mitochondrial dysfunction in 7-month-old mice was confirmed by reduction in the inner membrane integrity and increase in the activity of cytochrome c oxidase. The proteome analysis indicates that mitochondrial and overlapping metabolic alterations are adaptive upon aging, and may explain the synaptic pathology and cognitive impairment in the absence of neuronal loss. Animal models such as 7-month-old Tg2576 mice and tools to investigate synaptic alterations before appearance of neuronal death may help in understanding the pathological mechanisms occurring at early stages of AD. C1 [Cuadrado-Tejedor, Mar; Felipe Cabodevilla, Jesus; Zamarbide, Marta; Franco, Rafael; Perez-Mediavilla, Alberto] Univ Navarra, CIMA, Cellular & Mol Neuropharmacol Lab, E-31008 Pamplona, Spain. [Perez-Mediavilla, Alberto] Univ Navarra, Dept Biochem & Mol Biol, E-31008 Pamplona, Spain. [Cuadrado-Tejedor, Mar] Univ Navarra, Dept Anat, E-31008 Pamplona, Spain. [Gomez-Isla, Teresa] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Gomez-Isla, Teresa] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain. RP Perez-Mediavilla, A (reprint author), Univ Navarra, CIMA, Cellular & Mol Neuropharmacol Lab, Avda Pio XII,55, E-31008 Pamplona, Spain. EM lamediav@unav.es RI Franco, Rafael/C-3694-2015; Cuadrado-Tejedor, Mar/P-3387-2015; OI Franco, Rafael/0000-0003-2549-4919; Cuadrado-Tejedor, Mar/0000-0003-4260-9140 FU European Council DIADEM [QLRT-2000-02362]; Department of Education of the Government of Navarra, Spain; UTE project FIMA, Spain FX This study was supported by Grants from the European Council DIADEM QLRT-2000-02362, Department of Education of the Government of Navarra, and UTE project FIMA, Spain. NR 30 TC 14 Z9 14 U1 1 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD MAY PY 2013 VL 10 IS 4 BP 390 EP 405 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 136EV UT WOS:000318345600005 PM 23545067 ER PT J AU Markowitz, JT Alleyn, CA Phillips, R Muir, A Young-Hyman, D Laffel, LMB AF Markowitz, Jessica T. Alleyn, Cielo A. Phillips, Roxanne Muir, Andrew Young-Hyman, Deborah Laffel, Lori M. B. TI Disordered Eating Behaviors in Youth with Type 1 Diabetes: Prospective Pilot Assessment Following Initiation of Insulin Pump Therapy SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID ADOLESCENT FEMALES; MELLITUS; SAFETY; WOMEN; GIRLS AB Background: There is risk for disordered eating behaviors in type 1 diabetes, especially related to insulin manipulation. Implementation of insulin pump therapy may encourage either normalization of eating behaviors or a greater focus on food intake due to renewed emphasis on carbohydrate counting. There is need for prospective studies to assess disordered eating behaviors upon implementation of pump therapy using diabetes-specific measurement tools. Subjects and Methods: In a multicenter pilot study, 43 youth with type 1 diabetes, 10-17 years old, were assessed prior to pump initiation and after 1 and 6 months of pump therapy. Youth completed the Diabetes-specific Eating Problems Survey-Revised (DEPS-R), a validated measure of risk for both diabetes-specific and general disordered eating behaviors. Results: Youth (45% female), 13.3 years old with diabetes for 2.1 years, had a mean hemoglobin A1c of 8.3 +/- 1.3% (68 +/- 14.5 mmol/mol) at baseline. DEPS-R scores decreased over time (P = 0.01). Overall rate of high risk for eating disorders was low. Overweight/obese youth endorsed more disordered eating behaviors than normal-weight participants. DEPS-R scores were correlated with z-score for body mass index at all three time points and with hemoglobin A1c after 1 and 6 months. Hemoglobin A1c did not change significantly over the 6 months and was higher in overweight/obese compared with normal-weight participants. Conclusions: Initiation of insulin pump therapy was associated with diminished endorsement of disordered eating behaviors in youth with type 1 diabetes. Longer follow-up studies are needed to assess the impact of insulin pump therapy on glycemic control, weight status, and disordered eating behaviors in this vulnerable population. C1 [Markowitz, Jessica T.; Alleyn, Cielo A.; Phillips, Roxanne; Laffel, Lori M. B.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Pediat Adolescent & Adult Sect, Boston, MA 02215 USA. [Muir, Andrew] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Young-Hyman, Deborah] Georgia Hlth Sci Univ, Georgia Prevent Inst, Augusta, GA USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Pediat Adolescent & Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU American Diabetes Association Clinical Research Award [7-08-CR-66]; National Institute of Diabetes and Digestive and Kidney Diseases [1K23DK092335-01A1]; Eleanor Chesterman Beatson Fund; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund FX This work was funded by an American Diabetes Association Clinical Research Award (number 7-08-CR-66), a K23 award from the National Institute of Diabetes and Digestive and Kidney Diseases (number 1K23DK092335-01A1), the Eleanor Chesterman Beatson Fund, the Katherine Adler Astrove Youth Education Fund, and the Maria Griffin Drury Pediatric Fund. NR 15 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 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD MAY PY 2013 VL 15 IS 5 BP 428 EP 433 DI 10.1089/dia.2013.0008 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 137ZL UT WOS:000318477700011 PM 23550556 ER PT J AU Harrington, AT Clarridge, JE AF Harrington, Amanda T. Clarridge, Jill E., III TI Impact of identification of Streptococcus dysgalactiae subspecies equisimilis from throat cultures in an adult population SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Pharyngitis; Streptococcus dysgalactiae subspecies equisimilis; Throat culture ID BETA-HEMOLYTIC STREPTOCOCCI; GROUP-C STREPTOCOCCI; LANCEFIELD GROUP-C; ACUTE RHEUMATIC-FEVER; ACUTE PHARYNGITIS; GROUP-A; OUTBREAK; GLOMERULONEPHRITIS; INFECTION; ANGINOSUS AB Streptococcus dysgalactiae subspecies equisimilis (SDSE) are isolated from the throat of patients with pharyngitis, although the clinical significance remains debated. We sought to determine the incidence and association with pharyngitis of SDSE in an adult veteran population. Organisms were phenotypically identified to subspecies and Lancefield group, with selective 16S rRNA gene sequencing. From 833 throat cultures, the overall frequency of SDSE was 3.4% (64% group C and 36% group G) as compared to 8.6% for S. pyogenes (GAS). SDSE was described as a large colony in only 29% of the original culture evaluations by bench technologists, and clinical symptoms were similar for GAS and SDSE. Laboratory algorithms that are limited to identification of only GAS or are based on Lancefield group or visual identification of "large-colony type" beta hemolytic Lancefield group C and G streptococci may be missing or misidentifying SDSE along with Anginosus group streptococci. Published by Elsevier Inc. C1 [Clarridge, Jill E., III] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Clarridge, JE (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM jill.clarridge@va.gov NR 29 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 0732-8893 EI 1879-0070 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAY PY 2013 VL 76 IS 1 BP 20 EP 23 DI 10.1016/j.diagmicrobio.2013.02.029 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 135YF UT WOS:000318325900005 PM 23537788 ER PT J AU Camus, M Jensen, DM Ohning, GV Kovacs, TO Ghassemi, KA Jutabha, R Machicado, GA Dulai, GS Hines, OJ AF Camus, M. Jensen, D. M. Ohning, G. V. Kovacs, T. O. Ghassemi, K. A. Jutabha, R. Machicado, G. A. Dulai, G. S. Hines, O. J. TI Severe upper gastrointestinal hemorrhage from linear gastric ulcers in large hiatal hernias: a large prospective case series of Cameron ulcers SO ENDOSCOPY LA English DT Editorial Material ID DIAGNOSIS; ANEMIA AB We report a case series of all consecutive patients hospitalized in our two tertiary referral medical centers over the past 17 years for Cameron ulcers causing severe upper gastrointestinal hemorrhage (GIH) or severe obscure GIH. Cameron ulcers were diagnosed in 25 of the 3960 screened patients with severe upper GIH or severe obscure GIH (0.6%). Of these, 21 patients had a prospective follow-up (median time 20.4 months [interquartile range: 8.5-31.8]). Patients were more often elderly women with chronic anemia, always had large hiatal hernias, and were usually referred for obscure GIH. Twelve of the 21 patients (57%) were referred for surgery while being treated with high-dose proton pump inhibitors (PPIs). The other 9 patients (43 %) continued PPIs without any rebleeding during the follow-up. Cameron ulcers in large hiatal hernias are an uncommon cause of severe upper GIH. The choice of medical vs. surgical therapy should be individualized. C1 [Camus, M.; Jensen, D. M.; Ohning, G. V.; Kovacs, T. O.; Ghassemi, K. A.; Jutabha, R.; Machicado, G. A.; Dulai, G. S.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Hemostasis Res Grp, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Jensen, D. M.; Ohning, G. V.; Kovacs, T. O.; Ghassemi, K. A.; Jutabha, R.; Machicado, G. A.; Dulai, G. S.] Univ Calif Los Angeles, Ronald Reagan Med Ctr, Div Digest Dis, Los Angeles, CA USA. [Camus, M.] Univ Paris 07, Dept Gastroenterol, Lariboisiere Hosp, APHP, F-75221 Paris 05, France. [Jensen, D. M.; Ohning, G. V.; Kovacs, T. O.; Machicado, G. A.; Dulai, G. S.] Vet Affairs Greater Los Angeles Healthcare, Div Digest Dis, Los Angeles, CA USA. [Hines, O. J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. RP Camus, M (reprint author), Lariboisiere Hosp, APHP, Dept Gastroenterol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM marine.camus@gmail.com FU NIDDK NIH HHS [P30 DK041301] NR 9 TC 2 Z9 3 U1 0 U2 5 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD MAY PY 2013 VL 45 IS 5 BP 397 EP 400 DI 10.1055/s-0032-1326294 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 131VY UT WOS:000318026600010 PM 23616128 ER PT J AU Hasserjian, RP AF Hasserjian, Robert P. TI DIAGNOSTIC TESTING FOR BETA GLOBIN DEFECTS. ACUTE MYELOID LEUKEMIA: ADVANCES IN DIAGNOSIS AND CLASSIFICATION SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hasserjian, Robert P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD MAY PY 2013 VL 35 SU 1 SI SI BP 10 EP 10 PG 1 WC Hematology SC Hematology GA 135KF UT WOS:000318286300021 ER PT J AU Smock, K Ledford-Kraemer, M Meijer, P Hsu, P Van Cott, E AF Smock, Kristi Ledford-Kraemer, Marlies Meijer, Piet Hsu, Peihong Van Cott, Elizabeth TI UPDATE ON PROFICIENCY TEST RESULT S FOR HEPARIN-INDUCED THROMBOCYTOPENIA: A REPORT FROM THE NORTH AMERICAN SPECIALIZED COAGULATION LABORATORY ASSOCIATION (NASCOLA) SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Smock, Kristi] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA. [Ledford-Kraemer, Marlies] CLOT ED Inc, Islamorada, FL USA. [Meijer, Piet] ECAT Fdn, Leiden, Netherlands. [Hsu, Peihong] Hofstra North Shore Long Isl Jewish Sch Med, Dept Lab Med, Lake Success, NY USA. [Van Cott, Elizabeth] Massachusetts Gen Hosp, Dept Pathol, 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 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD MAY PY 2013 VL 35 SU 1 SI SI BP 16 EP 17 PG 2 WC Hematology SC Hematology GA 135KF UT WOS:000318286300032 ER PT J AU Van Cott, E AF Van Cott, Elizabeth TI COMMON SPECIAL COAGULATION ASSAYS-INSIGHTS FROM QUALITY ASSURANCE SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Van Cott, Elizabeth] Massachusetts Gen Hosp, Coagulat Lab, Boston, MA 02114 USA. [Van Cott, Elizabeth] Massachusetts Gen Hosp, Core Lab, 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 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD MAY PY 2013 VL 35 SU 1 SI SI BP 24 EP 24 PG 1 WC Hematology SC Hematology GA 135KF UT WOS:000318286300044 ER PT J AU Hasserjian, RP AF Hasserjian, Robert P. TI ACUTE MYELOID LEUKEMIA: ADVANCES IN DIAGNOSIS AND CLASSIFICATION SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hasserjian, Robert P.] Harvard Univ, Sch Med, Boston, MA 02114 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 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD MAY PY 2013 VL 35 SU 1 SI SI BP 36 EP 36 PG 1 WC Hematology SC Hematology GA 135KF UT WOS:000318286300068 ER PT J AU Hsu, PH Zantek, ND Meijer, P Brody, J Zhang, XM Smock, KJ Van Cott, EM AF Hsu, Peihong Zantek, Nicole D. Meijer, Piet Brody, Judith Zhang, Xinmin Smock, Kristi J. Van Cott, Elizabeth M. TI FACTOR XIII ASSAYS, A PROBLEM FOR LABORATORY DIAGNOSIS? AN ANALYSIS OF INTERNATIONAL PROFICIENCY TESTING RESULTS SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 [Hsu, Peihong; Brody, Judith; Zhang, Xinmin] Hofstra North Shore Long Isl Jewish Sch, Dept Pathol Lab Med, Lake Success, NY USA. [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Meijer, Piet] ECAT Fdn, NL-2300 AA Leiden, Netherlands. [Smock, Kristi J.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 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 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD MAY PY 2013 VL 35 SU 1 SI SI BP 68 EP 68 PG 1 WC Hematology SC Hematology GA 135KF UT WOS:000318286300134 ER PT J AU Bedair, H Lawless, B Malchau, H AF Bedair, Hany Lawless, Bryan Malchau, Henrik TI Are Implant Designer Series Believable? Comparison of Survivorship Between Designer Series and National Registries SO JOURNAL OF ARTHROPLASTY LA English DT Article DE implant; survivorship; registry; revision; failure ID TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; UNICOMPARTMENTAL KNEE ARTHROPLASTY; EARLY FAILURE; FEMORAL COMPONENT; REPLACEMENT AB Performance of hip and knee implants reported by the designing surgeon(s) is often felt to be more optimistic than those observed in non-designer series. The purpose of this study is to compare the survivorship of hip and knee prostheses in series reported by designers with those in national joint registries. Fifteen different hip and knee implant results published by designers were identified and compared to four national registries. Thirty-two percent of comparisons performed demonstrated greater survivorship in the designer series compared to the registry, while 0% reported lower, and 68% demonstrated no difference. Two implants accounted for the majority (12/16) of the discordances. There was a lower (62%) concordance rate between the registries than between the designer series and registries (68%). (C) 2013 Elsevier Inc. All rights reserved. C1 [Bedair, Hany; Lawless, Bryan; Malchau, Henrik] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bedair, H (reprint author), 55 Fruit St,Yawkey Suite 3B, Boston, MA 02114 USA. OI Malchau, Henrik/0000-0002-4291-2441 NR 22 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD MAY PY 2013 VL 28 IS 5 BP 728 EP 731 DI 10.1016/j.arth.2012.08.027 PG 4 WC Orthopedics SC Orthopedics GA 136SI UT WOS:000318383300004 PM 23414935 ER PT J AU Schuman-Olivier, Z Noordsy, DL Brunette, MF AF Schuman-Olivier, Zev Noordsy, Douglas L. Brunette, Mary F. TI Strategies for Reducing Antipsychotic Polypharmacy SO JOURNAL OF DUAL DIAGNOSIS LA English DT Article DE mindfulness; exercise; polypharmacy; antipsychotic; psychosis; schizophrenia; addiction; substance abuse; wellness; co-occurring disorder ID SUBSTANCE USE DISORDERS; STRESS REDUCTION PROGRAM; RANDOMIZED-CONTROLLED-TRIALS; MINDFULNESS-BASED THERAPY; COGNITIVE THERAPY; PHYSICAL-ACTIVITY; BIPOLAR DISORDER; ALCOHOL-USE; MOTIVATIONAL INTERVENTION; SCHIZOAFFECTIVE DISORDER AB Antipsychotic polypharmacy (the use of two or more antipsychotics at the same time) is an increasingly common practice even though consensus treatment guidelines do not recommend it. Multiple studies have examined algorithms, decision supports, and educational strategies to change prescriber behaviors. We describe the case study of a young adult with schizoaffective disorder who transferred from residential treatment to an outpatient assertive community treatment for co-occurring disorders, presenting treatment-resistant psychotic and mood disorder symptoms and experiencing intolerable side effects from substantial polypharmacy. This case exemplifies how integrating wellness-oriented strategies, such as mindfulness training and exercise, into treatment and encouraging people to apply these strategies to address persistent symptoms might facilitate reductions in antipsychotic polypharmacy among those with co-occurring disorders. (Journal of Dual Diagnosis, 9: 208-218, 2013) C1 [Schuman-Olivier, Zev; Brunette, Mary F.] WestBridge Community Serv, Medford, MA 02155 USA. [Schuman-Olivier, Zev] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA USA. [Noordsy, Douglas L.; Brunette, Mary F.] Geisel Sch Med Dartmouth, Psychiat Res Ctr, Lebanon, NH USA. RP Schuman-Olivier, Z (reprint author), WestBridge Community Serv, 275 Myst Ave,Suite C, Medford, MA 02155 USA. EM zschuman@westbridge.org NR 118 TC 1 Z9 1 U1 3 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 J9 J DUAL DIAGN JI J. Dual Diagn. PD MAY 1 PY 2013 VL 9 IS 2 BP 208 EP 218 DI 10.1080/15504263.2013.778767 PG 11 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA 136IA UT WOS:000318354400015 ER PT J AU Partin, MR Powell, AA Burgess, JF AF Partin, Melissa R. Powell, Adam A. Burgess, James F., Jr. TI Fecal Occult Blood Test (FOBT) Overuse reply SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter C1 [Partin, Melissa R.; Powell, Adam A.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. RP Partin, MR (reprint author), Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, 1 Vet Dr, Minneapolis, MN 55417 USA. EM Melissa.partin@va.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2013 VL 28 IS 5 BP 611 EP 611 DI 10.1007/s11606-013-2397-1 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 131IG UT WOS:000317985900006 PM 23475642 ER PT J AU Saha, S Korthuis, PT Cohn, JA Sharp, VL Moore, RD Beach, MC AF Saha, Somnath Korthuis, P. Todd Cohn, Jonathan A. Sharp, Victoria L. Moore, Richard D. Beach, Mary Catherine TI Primary Care Provider Cultural Competence and Racial Disparities in HIV Care and Outcomes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE culture; ethnic groups; HIV ID PATIENT-PHYSICIAN RELATIONSHIP; ACTIVE ANTIRETROVIRAL THERAPY; SELF-REPORTED ADHERENCE; HEALTH-CARE; UNITED-STATES; MEDICATION ADHERENCE; INFECTED ADULTS; QUALITY; COMMUNICATION; MORTALITY AB Health professional organizations have advocated for increasing the "cultural competence" (CC) of healthcare providers, to reduce racial and ethnic disparities in patient care. It is unclear whether provider CC is associated with more equitable care. To evaluate whether provider CC is associated with quality of care and outcomes for patients with HIV/AIDS. Survey of 45 providers and 437 patients at four urban HIV clinics in the U.S. Providers' self-rated CC was measured using a novel, 20-item instrument. Outcome measures included patients' receipt of antiretroviral (ARV) therapy, self-efficacy in managing medication regimens, complete 3-day ARV adherence, and viral suppression. Providers' mean age was 44 years; 56 % were women, and 64 % were white. Patients' mean age was 45; 67 % were men, and 77 % were nonwhite. Minority patients whose providers scored in the middle or highest third on self-rated CC were more likely than those with providers in the lowest third to be on ARVs, have high self-efficacy, and report complete ARV adherence. Racial disparities were observed in receipt of ARVs (adjusted OR, 95 % CI for white vs. nonwhite: 6.21, 1.50-25.7), self-efficacy (3.77, 1.24-11.4), and viral suppression (13.0, 3.43-49.0) among patients of low CC providers, but not among patients of moderate and high CC providers (receipt of ARVs: 0.71, 0.32-1.61; self-efficacy: 1.14, 0.59-2.22; viral suppression: 1.20, 0.60-2.42). Provider CC was associated with the quality and equity of HIV care. These findings suggest that enhancing provider CC may reduce racial disparities in healthcare quality and outcomes. C1 [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97239 USA. [Saha, Somnath; Korthuis, P. Todd] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Cohn, Jonathan A.] Wayne State Univ, Sch Med, Dept Med, Div Infect Dis, Detroit, MI 48201 USA. [Sharp, Victoria L.] St Lukes Roosevelt Hosp, Ctr Comprehens Care, New York, NY USA. [Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. RP Saha, S (reprint author), Portland VA Med Ctr, Gen Internal Med Sect, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sahas@ohsu.edu FU Health Resources and Services Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; Department of Veterans Affairs; Generalist Physician Faculty Scholar awards from the Robert Wood Johnson Foundation; National Institute on Drug Abuse [K23 DA019809] FX This research was supported by a contract from the Health Resources and Services Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). Representatives of both funding agencies were involved in the design of the study, but not in its conduct; in collection, management, analysis, or interpretation of the data; or in preparation, review, or approval of the manuscript. Drs. Saha, Moore, and Beach 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. Dr. Saha was supported by the Department of Veterans Affairs. Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05), and both Drs. Saha and Beach were supported by Generalist Physician Faculty Scholar awards from the Robert Wood Johnson Foundation. Dr. Korthuis was supported by the National Institute on Drug Abuse (K23 DA019809). The views expressed in this article are those of the authors, and no official endorsement by the Agency for Healthcare Research and Quality, the Department of Veterans Affairs, or the U.S. Department of Health and Human Services is intended or should be inferred. NR 53 TC 18 Z9 18 U1 1 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2013 VL 28 IS 5 BP 622 EP 629 DI 10.1007/s11606-012-2298-8 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 131IG UT WOS:000317985900008 PM 23307396 ER PT J AU Marshall, R Beach, MC Saha, S Mori, T Loveless, MO Hibbard, JH Cohn, JA Sharp, VL Korthuis, PT AF Marshall, Rebecca Beach, Mary Catherine Saha, Somnath Mori, Tomi Loveless, Mark O. Hibbard, Judith H. Cohn, Jonathan A. Sharp, Victoria L. Korthuis, P. Todd TI Patient Activation and Improved Outcomes in HIV-Infected Patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient activation; HIV; self-efficacy; medication adherence; patient outcomes ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY ADHERENCE; SELF-MANAGEMENT; MEDICATION ADHERENCE; REPORTED ADHERENCE; CHRONIC DISEASE; UNITED-STATES; MEASURE PAM; VIRAL LOAD; HEALTH AB The Patient Activation Measure (PAM) assesses several important concepts in chronic care management, including self-efficacy for positive health behaviors. In HIV-infected populations, better self-efficacy for medication management is associated with improved adherence to antiretroviral medications (ARVs), which is critically important for controlling symptoms and slowing disease progression. To determine 1) characteristics associated with patient activation and 2) associations between patient activation and outcomes in HIV-infected patients. Cross-sectional survey. 433 patients receiving care in four HIV clinics. An interviewer conducted face-to-face interviews with patients following their HIV clinic visit. Survey data were supplemented with medical record abstraction to obtain most recent CD4 counts, HIV viral load and antiretroviral medications. Patient activation was measured using the 13-item PAM (possible range 0-100). Outcomes included CD4 cell count > 200 cells/mL(3), HIV-1 RNA < 400 copies/mL (viral suppression), and patient-reported adherence. Overall, patient activation was high (mean PAM = 72.3 [SD 16.5, range 34.7-100]). Activation was lower among those without vs. with a high school degree (68.0 vs. 74.0, p < .001), and greater depression (77.6 lowest, 70.2 middle, 68.1 highest tertile, p < .001). There was no association between patient activation and age, race, gender, problematic alcohol use, illicit drug use, or social status. In multivariable models, every 5-point increase in PAM was associated with greater odds of CD4 count > 200 cells/mL(3) (aOR 1.10 [95 % CI 1.01, 1.21]), adherence (aOR 1.18 [95 % CI 1.09, 1.29]) and viral suppression (aOR 1.08 [95 % CI 1.00, 1.17]). The association between PAM and viral suppression was mediated through adherence. Higher patient activation was associated with more favorable HIV outcomes. Interventions to improve patient activation should be developed and tested for their ability to improve HIV outcomes. C1 [Marshall, Rebecca] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Saha, Somnath; Korthuis, P. Todd] Oregon Hlth & Sci Univ, Div Gen Internal Med, Portland, OR 97201 USA. [Saha, Somnath; Mori, Tomi; Loveless, Mark O.; Hibbard, Judith H.; Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Hibbard, Judith H.] Univ Oregon, Dept Planning Publ Policy & Management, Eugene, OR 97403 USA. [Cohn, Jonathan A.] Wayne State Univ, Sch Med, Dept Med, Div Infect Dis, Detroit, MI 48201 USA. [Sharp, Victoria L.] St Lukes Roosevelt Hosp, Ctr Comprehens Care, New York, NY USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu FU Health Resources Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08 HS013903-05]; National Institutes of Health, National Institute on Drug Abuse [K23DA019809]; Robert Wood Johnson Generalist Physician Faculty Scholars Awards; Department of Veterans Affairs FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). Dr. Korthuis' time was supported by the National Institutes of Health, National Institute on Drug Abuse (K23DA019809). Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05), and both Dr. Beach and Dr. Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. Dr. Saha is supported by the Department of Veterans Affairs. The contents of the publication are solely the responsibility of the authors and do not necessarily represent the views of the funding agencies or the U.S. government. NR 41 TC 25 Z9 26 U1 6 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2013 VL 28 IS 5 BP 668 EP 674 DI 10.1007/s11606-012-2307-y PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 131IG UT WOS:000317985900014 PM 23288378 ER PT J AU Bryson, CL Au, DH Maciejewski, ML Piette, JD Fihn, SD Jackson, GL Perkins, M Wong, ES Yano, EM Liu, CF AF Bryson, Chris L. Au, David H. Maciejewski, Matthew L. Piette, John D. Fihn, Stephan D. Jackson, George L. Perkins, Mark Wong, Edwin S. Yano, Elizabeth M. Liu, Chuan-Fen TI Wide Clinic-Level Variation in Adherence to Oral Diabetes Medications in the VA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pharmacoepidemiology; health services research; diabetes; veterans; primary care ID MYOCARDIAL-INFARCTION; SELF-CARE; MANAGEMENT; IMPROVEMENT AB While there has been extensive research into patient-specific predictors of medication adherence and patient-specific interventions to improve adherence, there has been little examination of variation in clinic-level medication adherence. We examined the clinic-level variation of oral hypoglycemic agent (OHA) medication adherence among patients with diabetes treated in the Department of Veterans Affairs (VA) primary care clinics. We hypothesized that there would be systematic variation in clinic-level adherence measures, and that adherence within organizationally-affiliated clinics, such as those sharing local management and support, would be more highly correlated than adherence between unaffiliated clinics. Retrospective cohort study. VA hospital and VA community-based primary care clinics in the contiguous 48 states. 444,418 patients with diabetes treated with OHAs and seen in 158 hospital-based clinics and 401 affiliated community primary care clinics during fiscal years 2006 and 2007. Refill-based medication adherence to OHA. Adjusting for patient characteristics, the proportion of patients adherent to OHAs ranged from 57 % to 81 % across clinics. Adherence between organizationally affiliated clinics was high (Pearson Correlation = 0.82), and adherence between unaffiliated clinics was low (Pearson Correlation = 0.04). The proportion of patients adherent to OHAs varied widely across VA primary care clinics. Clinic-level adherence was highly correlated to other clinics in the same organizational unit. Further research should identify which factors common to affiliated clinics influence medication adherence. C1 [Bryson, Chris L.; Au, David H.; Perkins, Mark; Wong, Edwin S.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Bryson, Chris L.; Au, David H.; Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA USA. [Maciejewski, Matthew L.; Jackson, George L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.; Jackson, George L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Piette, John D.] VA Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Fihn, Stephan D.] Univ Washington, Dept Vet Affairs, Off Analyt & Business Intelligence, Seattle, WA 98195 USA. [Wong, Edwin S.; Liu, Chuan-Fen] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. [Yano, Elizabeth M.] Los Angeles VA, Ctr Study Healthcare Provider Behav, Los Angeles, VA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. [Bryson, Chris L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. RP Bryson, CL (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Christopher.Bryson@va.gov FU Department of Veterans Affairs, Health Services Research and Development [IIR 07-068-2]; VA Career Development Award [03-177]; VA Health Services Research and Development Postdoctoral Fellowship [TPP 61-024]; Bosch Inc.; Gilead Sciences; Takeda Pharmaceuticals; Novartis; Surgical Review Corporation FX This research was supported by an Investigator Initiated Research Award (IIR 07-068-2) from the Department of Veterans Affairs, Health Services Research and Development. Dr. Bryson was supported by VA Career Development Award 03-177. Dr. Jackson was supported for a portion of this project by a VA Career Development Award. Dr. Piette is a VA Senior Research Career Scientist; Dr. Maciejewski and Dr. Yano are VA Research Career Scientists. Dr. Wong was supported by VA Health Services Research and Development Postdoctoral Fellowship TPP 61-024. An earlier version of this manuscript was presented as a poster at the Society of General Internal Medicine 32nd Annual Meeting in Miami, FL in 2009. Dr. Bryson takes responsibility for the integrity of the data and the accuracy of the data analysis. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.; All authors are federal employees for the Department of Veterans Affairs. Dr. Au has received consultation funds from Bosch Inc. and a grant from Gilead Sciences. Dr. Maciejewski has received consultation funds from Takeda Pharmaceuticals, Novartis and the Surgical Review Corporation. Dr. Maciejewski also owns stock in Amgen. NR 27 TC 5 Z9 5 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2013 VL 28 IS 5 BP 698 EP 705 DI 10.1007/s11606-012-2331-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 131IG UT WOS:000317985900018 PM 23371383 ER PT J AU Jubelt, LE AF Jubelt, Lindsay E. TI Capsule Commentary on Melzer et.al., Missing Potential Opportunities to Reduce Repeat COPD Exacerbations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Jubelt, Lindsay E.] Univ Penn, Perelman Sch Med, Robert Wood Johnson Fdn Clin Scholars, Philadelphia, PA 19104 USA. [Jubelt, Lindsay E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Jubelt, Lindsay E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Jubelt, LE (reprint author), Univ Penn, Perelman Sch Med, Robert Wood Johnson Fdn Clin Scholars, Philadelphia, PA 19104 USA. EM ljubelt@upenn.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2013 VL 28 IS 5 BP 708 EP 708 DI 10.1007/s11606-012-2299-7 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 131IG UT WOS:000317985900021 PM 23288376 ER PT J AU Bryan, T Snyder, E AF Bryan, Teresa Snyder, Erin TI The Clinical Breast Exam: A Skill that Should Not Be Abandoned SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE clinical breast exam; women's health; medical education; simulation ID SIGNIFICANT NUMBER; SCREENING-PROGRAM; NORMAL MAMMOGRAM; WOMEN PRESENT; CANCER EVEN; PERFORMANCE; SYMPTOMS; PATIENT; TRIAL AB The clinical breast exam (CBE) is an important tool in the care of women. However, the utility of the screening CBE has been called into question. This article discusses the importance of the CBE as a physical diagnosis tool. Recommendations regarding screening with CBE are reviewed, and evidence surrounding breast cancer screening using CBE is briefly summarized. Clinicians should strive to provide high quality CBEs as part of the general clinical exam for women, particularly those who present with breast complaints, and for patients who choose to have CBE screening. In conclusion, there is a role for the CBE in the care of women, and clinicians should be proficient at performing these exams. Simulation teaching technologies are now available at Department of Veteran Affairs (VA) facilities to enable clinicians to improve their CBE skills. C1 [Bryan, Teresa; Snyder, Erin] Univ Alabama Birmingham, Med Sch Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Bryan, T (reprint author), Univ Alabama Birmingham, Med Sch Birmingham, Birmingham Vet Affairs Med Ctr, FOT 720 1720 2nd Ave South, Birmingham, AL 35294 USA. EM Teresa.bryan@va.gov NR 28 TC 8 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2013 VL 28 IS 5 BP 719 EP 722 DI 10.1007/s11606-013-2373-9 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 131IG UT WOS:000317985900025 PM 23435772 ER PT J AU Huetsch, JC Uman, JE Udris, EM Au, DH AF Huetsch, John C. Uman, Jane E. Udris, Edmunds M. Au, David H. TI Predictors of Adherence to Inhaled Medications among Veterans with COPD (vol 27, pg 1506, 2012) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Correction C1 [Huetsch, John C.; Uman, Jane E.; Udris, Edmunds M.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Huetsch, John C.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Huetsch, JC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2013 VL 28 IS 5 BP 743 EP 747 DI 10.1007/s11606-013-2377-5 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 131IG UT WOS:000317985900032 ER PT J AU Kara, A McQuillan, P Dhaliwal, G AF Kara, Areeba McQuillan, Patrick Dhaliwal, Gurpreet TI A multifaceted case SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID POSTSURGICAL GOUT; HYPERURICEMIA; RISK; PRESENTATIONS; POPULATION; PREVALENCE; MANAGEMENT; HEALTH; US C1 [Kara, Areeba; McQuillan, Patrick] Indiana Univ Hlth Phys, Dept Inpatient Med, Indianapolis, IN 46202 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Kara, A (reprint author), Indiana Univ Hlth Phys, Dept Inpatient Med, 1633 N Capitol Ave, Indianapolis, IN 46202 USA. EM akara@iuhealth.org NR 22 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2013 VL 8 IS 5 BP 267 EP 270 DI 10.1002/jhm.2043 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 139ZS UT WOS:000318624400007 PM 23606357 ER PT J AU Blumenthal, D Jena, AB AF Blumenthal, Daniel Jena, Anupam B. TI Hospital value-based purchasing SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID QUALITY-OF-CARE; READMISSION RATES; PERFORMANCE; PAY; MORTALITY; MEDICARE; ASSOCIATION; INTENSITY; IMPACT; INCENTIVES AB Hospital Value Based Purchasing (VBP) aims to incentivize inpatient providers to delivery high value, as opposed to high volume, health care. The formal mandate of hospitals to provide high value health care through financial incentives marks an important change in Medicare and Medicaid policy. In this opportune review of VBP, we discuss the relevant historical changes in the reimbursement environment of U.S. hospitals that have set the stage for VBP. We describe the structure of the Centers for Medicare and Medicaid Services' VBP program, with a focus on which hospitals are eligible to participate in the program, the specific outcomes measured and incentivized, how rewards and penalties are allocated, and how the program will be funded. In an effort to anticipate some of the issues that lie ahead, we then highlight a number of potential challenges to the success of VBP, and discuss how VBP will impact the delivery and reimbursement of inpatient care services. We conclude by examining how the VBP program is likely to evolve over time. Journal of Hospital Medicine 2013;8:271277. (c) 2013 Society of Hospital Medicine C1 [Blumenthal, Daniel] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Cambridge, MA USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu NR 36 TC 17 Z9 17 U1 3 U2 20 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 MAY PY 2013 VL 8 IS 5 BP 271 EP 277 DI 10.1002/jhm.2045 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 139ZS UT WOS:000318624400008 PM 23589485 ER PT J AU Sperduto, PW Kased, N Roberge, D Chao, ST Shanley, R Luo, XH Sneed, PK Suh, J Weil, RJ Jensen, AW Brown, PD Shih, HA Kirkpatrick, J Gaspar, LE Fiveash, JB Chiang, V Knisely, JPS Sperduto, CM Lin, N Mehta, M AF Sperduto, Paul W. Kased, Norbert Roberge, David Chao, Samuel T. Shanley, Ryan Luo, Xianghua Sneed, Penny K. Suh, John Weil, Robert J. Jensen, Ashley W. Brown, Paul D. Shih, Helen A. Kirkpatrick, John Gaspar, Laurie E. Fiveash, John B. Chiang, Veronica Knisely, Jonathan P. S. Sperduto, Christina Maria Lin, Nancy Mehta, Minesh TI The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Breast cancer; Brain metastases; Prognosis; Radiation therapy; Stereotactic radiosurgery; Estrogen; Progesterone; HER2; Graded prognostic assessment ID GRADED PROGNOSTIC ASSESSMENT; RADIATION-THERAPY; RECEPTOR; HER-2 AB Our group has previously published the Diagnosis-Specific Graded Prognostic Assessment (GPA) showing the prognostic factors associated with survival in patients with brain metastases (BM). The purpose of this study is to investigate the relationship of breast cancer subtype to the time interval from primary diagnosis (PD) to development of BM (TPDBM), number of BM at initial BM presentation and survival. We analyzed our previously described multi-institutional retrospective database of 865 breast cancer patients treated for newly-diagnosed BM from 1993 to 2010. Several factors found to be associated with survival were incorporated into the Breast-GPA, including tumor subtype. The GPA database was further analyzed to determine if the subtype correlated with the TPDBM, number of BM, and survival from PD. After exclusions for incomplete data, 383 patients remained eligible for analysis. The subtypes were approximated as follows: Luminal B: triple positive; HER2: HER2 positive/ER/PR negative; Luminal A; ER/PR positive/HER2 negative; Basal: triple negative. Patients with Basal (90), HER2 (119), Luminal B (98) and Luminal A (76) tumor subtypes had a median TPDBM of 27.5, 35.8, 47.4 and 54.4 months (p < 0.01), median survival from PD of 39.6, 66.4, 90.3 and 72.7 months (p < 0.01) and median survival from BM of 7.3, 17.9, 22.9 and 10.0 months (p < 0.01), respectively. Tumor subtype is an important prognostic factor for survival in patients with breast cancer and BM. Although TPDBM is not an independent prognostic factor for survival (and thus not part of the Breast-GPA), the TPDBM does correlate with tumor subtype but does not correlate with the number of BM. Patients with Basal and HER2 tumor subtypes have short TPDBM. Prospective studies are needed to determine if screening brain MRIs are indicated in patients with Basal or HER2 subtypes. C1 [Sperduto, Paul W.] Univ Minnesota, Minneapolis, MN USA. [Kased, Norbert; Sneed, Penny K.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Roberge, David] Univ Montreal, Notre Dame Hosp, Montreal, PQ H3C 3J7, Canada. [Chao, Samuel T.; Suh, John] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Shanley, Ryan; Luo, Xianghua] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Sneed, Penny K.; Weil, Robert J.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Jensen, Ashley W.] Sanford Roger Maris Canc Ctr, Dept Radiat Oncol, Fargo, ND USA. [Brown, Paul D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Shih, Helen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kirkpatrick, John] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Gaspar, Laurie E.] Univ Colorado, Sch Med, Dept Radiat Oncol, Aurora, CO USA. [Fiveash, John B.] Univ Alabama Birmingham, Med Ctr, Birmingham, AL 35294 USA. [Chiang, Veronica] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Chiang, Veronica] Yale Canc Ctr, New Haven, CT USA. [Knisely, Jonathan P. S.] Hofstra Univ, Sch Med, Dept Radiat Med, Manhasset, NY USA. [Knisely, Jonathan P. S.] North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. [Sperduto, Christina Maria] Dartmouth Coll, Hanover, NH 03755 USA. [Lin, Nancy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mehta, Minesh] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Sperduto, PW (reprint author), 560 S Maple St,Suite 10, Waconia, MN 55387 USA. EM psperduto@mropa.com OI Kirkpatrick, John/0000-0002-4019-0350; mehta, minesh/0000-0002-4812-5713 FU U.S. Department of Defense Breast Cancer Research Program [W81XWH-062-0033]; NIH [P30- CA77598] FX Dr. Mehta has served as a consultant to Abbott, Bristol-Meyers-Squibb, Elekta, Genentech, Merck, Novartis, Novo-cure, Tomotherapy and Viewray; he serves on the Board of Directors of Pharmacyclics, He holds stock options in Pharmacyclics and Accuray. Dr. Lin has served as a consultant to Novartis (<$ 10 K) and GlaxoSmithKline (<$ 10 K). Grant Support This research was supported in part by Grant W81XWH-062-0033 from the U.S. Department of Defense Breast Cancer Research Program, to RJW, and by NIH Grant P30- CA77598 utilizing the services of the Biostatistics Core, Masonic Cancer Center, University of Minnesota shared resource. NR 16 TC 28 Z9 29 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2013 VL 112 IS 3 BP 467 EP 472 DI 10.1007/s11060-013-1083-9 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 131GR UT WOS:000317981300018 PM 23462853 ER PT J AU Vajro, P Paolella, G Fasano, A AF Vajro, Pietro Paolella, Giulia Fasano, Alessio TI Microbiota and Gut-Liver Axis: Their Influences on Obesity and Obesity-Related Liver Disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review DE gut dysbiosis; gut-liver axis; inflammasome; intestinal permeability; nonalcoholic fatty liver disease; zonulin ID INTESTINAL BARRIER FUNCTION; INDUCED HEPATIC STEATOSIS; HIGH-FAT DIET; NONALCOHOLIC STEATOHEPATITIS; METABOLIC SYNDROME; PEDIATRIC OBESITY; BODY-WEIGHT; PROBIOTICS; INFLAMMATION; INSULIN AB A specific bacterial gut microbiota profile with increased extraction of energy has recently been associated with obesity, which has been shown to be a transmissible phenotype by microbiota transplantation. At the same time, there is now increasing evidence that gut microbiota plays a role in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis. This review summarizes well known and unexpected interacting factors leading to obesity and its related hepatic diseases, including intestinal mucosal permeability and its regulation, gut microbiota and translocation of its biological products, and gut-associated lymphoid tissue. These intestinal factors dictate also the balance between tolerance and immune response, which are critical for most of the complications in near and far organs or systems. We review novel mechanisms involving the development of gut permeability and adipose tissue plasticity, for example, the cross-talk between the gut microbiota, lipopolysaccharide, high-fat diet, and the endocannabinoid system tone, which have not been fully explored. Interactions between gut microbiota and other factors (eg, inflammasome deficiency) also are reviewed as emerging but far from being completely elucidated mechanisms influencing the onset of obesity and nonalcoholic fatty liver disease. C1 [Vajro, Pietro; Paolella, Giulia] Univ Salerno, Sch Med, I-84081 Baronissi, Sa, Italy. [Vajro, Pietro; Paolella, Giulia] ELFID, Naples, Italy. [Fasano, Alessio] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. RP Vajro, P (reprint author), Univ Salerno, Chair Pediat, Dept Med & Surg, I-84081 Baronissi, Sa, Italy. EM pvajro@unisa.it OI VAJRO, PIetro/0000-0002-9418-5880 FU National Institutes of Health grant [DK-48373]; FARB-ex grant FX This article was partially supported by the National Institutes of Health grant DK-48373 to A.F. and FARB-ex 60% 2012 grant to P.V. NR 51 TC 42 Z9 43 U1 3 U2 42 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 2013 VL 56 IS 5 BP 461 EP 468 DI 10.1097/MPG.0b013e318284abb5 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 131UK UT WOS:000318021900009 PM 23287807 ER PT J AU Sinha, M Stanley, TL Webb, J Scirica, C Corey, K Pratt, J Boepple, PA Hoppin, A Misra, M AF Sinha, Manasi Stanley, Takara L. Webb, Jessica Scirica, Christina Corey, Kathleen Pratt, Janey Boepple, Paul A. Hoppin, Alison Misra, Madhusmita TI Metabolic Effects of Roux-en-Y Gastric Bypass in Obese Adolescents and Young Adults SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE adolescence; glucose; high-sensitivity C-reactive protein; obesity; roux-en-Y gastric bypass ID BLOOD-CELL COUNT; WEIGHT-LOSS; BARIATRIC SURGERY; MEDICAL THERAPY AB Weight loss surgery is an increasingly common treatment option for obese adolescents, but data are limited regarding the metabolic effects of surgical weight loss procedures. We performed a retrospective review of the electronic medical record to determine metabolic outcomes for 24 adolescents and young adults ages 15 to 22 years undergoing Roux-en-Y gastric bypass from 2009 to 2011 as well as 24 age-, sex-, and BMI-matched controls. During a median follow-up of 6 months after Roux-en-Y gastric bypass, fasting glucose, hemoglobin A1c, low-density lipoprotein, triglyceride, and high-sensitivity C-reactive protein decreased significantly. Changes in these measures were not significantly associated with age or extent of weight loss. C1 [Sinha, Manasi; Stanley, Takara L.; Webb, Jessica; Boepple, Paul A.; Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Scirica, Christina; Corey, Kathleen; Pratt, Janey; Hoppin, Alison] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stanley, TL (reprint author), Massachusetts Gen Hosp, LON5-207, Boston, MA 02114 USA. EM tstanley@partners.org FU National Institutes of Health [T32HD052961, K23DK089910]; MGH Multicultural Affairs Office Summer Research Trainee Program; American Association for the Study of Liver Disease Clinical and Translational Research Award FX Funding provided in part by National Institutes of Health T32HD052961 to M. S. and K23DK089910 to T. L. S., by the MGH Multicultural Affairs Office Summer Research Trainee Program to J.W., and by the American Association for the Study of Liver Disease Clinical and Translational Research Award to K.C. NR 19 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 2013 VL 56 IS 5 BP 528 EP 531 DI 10.1097/MPG.0b013e318283910c PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 131UK UT WOS:000318021900020 PM 23274343 ER PT J AU Kaplan, JL Goldstein, AM Shenoy-Bhangle, A Badizadegan, K AF Kaplan, Jess L. Goldstein, Allan M. Shenoy-Bhangle, Anuradha Badizadegan, Kamran TI Neuromuscular and Vascular Hamartoma of the Small Intestine in a Child SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID SMALL-BOWEL; NEUROMESENCHYMAL-HAMARTOMA; DISEASE C1 [Kaplan, Jess L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Gastroenterol & Nutr, Boston, MA USA. [Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. [Shenoy-Bhangle, Anuradha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Radiol, Boston, MA USA. [Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kaplan, JL (reprint author), Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM jlkaplan@partners.org NR 8 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 2013 VL 56 IS 5 BP E33 EP E35 DI 10.1097/MPG.0b013e3182540e7f PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 131UK UT WOS:000318021900004 PM 22411271 ER PT J AU Davidson, CL Wingate, LR AF Davidson, Collin L. Wingate, LaRicka R. TI The glass half-full or a hopeful outlook: Which explains more variance in interpersonal suicide risk in a psychotherapy clinic sample? SO JOURNAL OF POSITIVE PSYCHOLOGY LA English DT Article DE positive psychology; optimism; hope; suicide; interpersonal psychological theory ID COPING SELF-EFFICACY; DISPOSITIONAL OPTIMISM; DEPRESSIVE SYMPTOMS; SOCIAL SUPPORT; PSYCHOLOGICAL ADJUSTMENT; POSTPARTUM DEPRESSION; INDIVIDUAL-DIFFERENCES; COLLEGE-STUDENTS; BREAST-CANCER; TRAIT ANXIETY AB Recent research has suggested that constructs in the field of positive psychology may be important for understanding suicide risk. Specifically, both hope theory and dispositional optimism have been linked to lower levels of suicidal ideation and interpersonal suicide risk. Despite these encouraging findings, no study has investigated the relationships between hope, optimism, and suicide risk in a clinical sample. The current study aimed to address this gap and to determine if hope or optimism was more important for understanding suicide risk as operationalized by the interpersonal-psychological theory and suicidal ideation. Results of hierarchical regression analyses revealed that both hope and optimism predicted lower levels of burdensomeness and thwarted belongingness, but were not significant predictors of suicidal ideation. Further, results revealed that when both hope and optimism were entered into a hierarchical regression in the final step, only optimism remained significant. Theoretical and clinical implications of these findings are discussed. C1 [Davidson, Collin L.] Denver VA Med Ctr, Denver, CO 80220 USA. [Wingate, LaRicka R.] Oklahoma State Univ, Stillwater, OK 74078 USA. RP Davidson, CL (reprint author), Denver VA Med Ctr, AVA VISN 19 MIRECC,1055 Clermont St, Denver, CO 80220 USA. EM collin.davidson@okstate.edu NR 63 TC 3 Z9 3 U1 2 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1743-9760 J9 J POSIT PSYCHOL JI J. Posit. Psychol. PD MAY 1 PY 2013 VL 8 IS 3 BP 263 EP 272 DI 10.1080/17439760.2013.787446 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 135MA UT WOS:000318291000008 ER PT J AU Brown, D Lu, HAJ AF Brown, Dennis Lu, Hua A. Jenny TI Aquaporin-2 Inhibitors: Fishing in the Chemical Pool SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID PLASMA-MEMBRANE; IN-VIVO; AQP2; PHOSPHORYLATION; CELLS; RATS C1 Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, 185 Cambridge St,CPZN 8150, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu FU NIDDK NIH HHS [DK96586, P30 DK057521, R01 DK096586] NR 12 TC 0 Z9 0 U1 0 U2 9 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2013 VL 24 IS 5 BP 685 EP 686 DI 10.1681/ASN.2013030243 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 134JZ UT WOS:000318207800001 PM 23599384 ER PT J AU Roshanravan, B Robinson-Cohen, C Patel, KV Ayers, E Littman, AJ de Boer, IH Ikizler, TA Himmelfarb, J Katzel, LI Kestenbaum, B Seliger, S AF Roshanravan, Baback Robinson-Cohen, Cassianne Patel, Kushang V. Ayers, Ernest Littman, Alyson J. de Boer, Ian H. Ikizler, T. Alp Himmelfarb, Jonathan Katzel, Leslie I. Kestenbaum, Bryan Seliger, Stephen TI Association between Physical Performance and All-Cause Mortality in CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; FUNCTIONING OLDER-ADULTS; CHRONIC-RENAL-FAILURE; INSULIN-RESISTANCE; BODY-COMPOSITION; CYSTATIN-C; CARDIOVASCULAR HEALTH; HEMODIALYSIS-PATIENTS; COGNITIVE IMPAIRMENT; ENERGY-METABOLISM AB In older adults, measurements of physical performance assess physical function and associate with mortality and disability. Muscle wasting and diminished physical performance often accompany CKD, resembling physiologic aging, but whether physical performance associates with clinical outcome in CKD is unknown. We evaluated 385 ambulatory, stroke-free participants with stage 2-4 CKD enrolled in clinic-based cohorts at the University of Washington and University of Maryland and Veterans Affairs Maryland Healthcare systems. We compared handgrip strength, usual gait speed, timed up and go (TUAG), and 6-minute walking distance with normative values and constructed Cox proportional hazards models and receiver operating characteristic curves to test associations with all-cause mortality. Mean age was 61 years and the mean estimated GFR was 41 ml/min per 1.73 m(2). Measures of lower extremity performance were at least 30% lower than predicted, but handgrip strength was relatively preserved. Fifty deaths occurred during the median 3-year follow-up period. After adjustment, each 0.1-m/s decrement in gait speed associated with a 26% higher risk for death, and each 1-second longer TUAG associated with an 8% higher risk for death. On the basis of the receiver operating characteristic analysis, gait speed and TUAG more strongly predicted 3-year mortality than kidney function or commonly measured serum biomarkers. Adding gait speed to a model that included estimated GFR significantly improved the prediction of 3-year mortality. In summary, impaired physical performance of the lower extremities is common in CKD and strongly associates with all-cause mortality. J Am Soc Nephrol 24: 822-830, 2013. doi: 10.1681/ASN.2012070702 C1 [Roshanravan, Baback; Ayers, Ernest; de Boer, Ian H.; Himmelfarb, Jonathan; Kestenbaum, Bryan] Univ Washington, Dept Med, Kidney Res Inst, Div Nephrol, Seattle, WA 98104 USA. [Robinson-Cohen, Cassianne; Littman, Alyson J.] Univ Washington, Dept Epidemiol, Kidney Res Inst, Seattle, WA 98104 USA. [Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98104 USA. [Littman, Alyson J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Ikizler, T. Alp] Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN USA. [Katzel, Leslie I.] Univ Maryland, Sch Med, Div Geriatr, Baltimore, MD 21201 USA. [Seliger, Stephen] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. RP Roshanravan, B (reprint author), Univ Washington, Dept Med, Kidney Res Inst, Div Nephrol, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM broshanr@u.washington.edu OI Robinson-Cohen, Cassianne/0000-0003-4783-7046 FU National Institutes of Health [R01-HL070938, K23-DK063079]; Kidney Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases [T32-DK007467-28, F32-K093235]; National Institute on Aging Claude D. Pepper Older Americans Independence Center [P30-AG028747]; Department of Veterans Affairs; Baltimore VAMC Geriatric Research Education and Clinical Center; Northwest Kidney Center Foundation; VA Rehabilitation Research and Development Career Development Award [6982]; VA Puget Sound Health Care System, Seattle, Washington; VA Maryland Healthcare System, Baltimore, Maryland FX This work was supported by grants from the National Institutes of Health (R01-HL070938 to J.H. and B.K. and K23-DK063079 to S.S.), the Kidney Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases (T32-DK007467-28 and F32-K093235 to B.R.), the VA Rehabilitation R&D Merit Review (to S.S. and L.K.), the National Institute on Aging Claude D. Pepper Older Americans Independence Center (P30-AG028747), the Department of Veterans Affairs, and the Baltimore VAMC Geriatric Research Education and Clinical Center, as well as an unrestricted grant from the Northwest Kidney Center Foundation. A.J.L. was supported by a VA Rehabilitation Research and Development Career Development Award (#6982). This study is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington, and the VA Maryland Healthcare System, Baltimore, Maryland. NR 41 TC 56 Z9 58 U1 2 U2 11 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2013 VL 24 IS 5 BP 822 EP 830 DI 10.1681/ASN.2012070702 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 134JZ UT WOS:000318207800016 PM 23599380 ER PT J AU Thames, AD Hinkin, CH Byrd, DA Bilder, RM Duff, KJ Mindt, MR Arentoft, A Streiff, V AF Thames, April D. Hinkin, Charles H. Byrd, Desiree A. Bilder, Robert M. Duff, Kimberley J. Mindt, Monica Rivera Arentoft, Alyssa Streiff, Vanessa TI Effects of Stereotype Threat, Perceived Discrimination, and Examiner Race on Neuropsychological Performance: Simple as Black and White? SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Stereotype threat; Performance anxiety; Neuropsychology; Perceived discrimination; Examiner-examinee racial discordance; Ethnicity ID WOMENS MATH PERFORMANCE; PICTURE-VOCABULARY TEST; AFRICAN-AMERICAN; RACIAL-DISCRIMINATION; TESTS; GAP; INTERVIEWER; PREVALENCE; MECHANISMS; EDUCATION AB The purpose of the current study was to examine the predictive roles of stereotype threat and perceived discrimination and the mediating role of examiner-examinee racial discordance on neuropsychological performance in a non-clinical sample of African American and Caucasian individuals. Ninety-two African American (n = 45) and Caucasian (n = 47) adults were randomly assigned to either a stereotype threat or non-threat condition. Within each condition, participants were randomly assigned to either a same race or different race examiner. All participants underwent neuropsychological testing and completed a measure of perceived discrimination. African Americans in the stereotype threat condition performed significantly worse on global NP (Mz = .30, 95% confidence interval [CI] [-0.07, -0.67] than African Americans in the non-threat condition (Mz = 0.09, CI [0.15, 0.33]. African Americans who reported high levels of perceived discrimination performed significantly worse on memory tests when tested by an examiner of a different race, Mz = -1.19, 95% CI [-1.78, -.54], than African Americans who were tested by an examiner of the same race, Mz = 0.24, 95% CI [-0.24, 0.72]. The current study underscores the importance of considering the role of contextual variables in neuropsychological performance, as these variables may obscure the validity of results among certain racial/ethnic groups. C1 [Thames, April D.; Hinkin, Charles H.; Bilder, Robert M.; Arentoft, Alyssa] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Hinkin, Charles H.; Arentoft, Alyssa; Streiff, Vanessa] Greater Los Angeles VA Healthcare Syst, Dept Psychol, Los Angeles, CA USA. [Byrd, Desiree A.; Mindt, Monica Rivera] Mt Sinai Sch Med, Dept Neurol & Psychiat, New York, NY USA. [Duff, Kimberley J.] Cerritos Coll, Dept Psychol, Norwalk, CA USA. [Mindt, Monica Rivera] Fordham Univ, Dept Psychol, New York, NY 10023 USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 740 Westwood Plaza C8-746, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu RI Thames, April/K-1964-2014; Bilder, Robert/A-8894-2008; OI Thames, April/0000-0001-8414-7189; Bilder, Robert/0000-0001-5085-7852; Arentoft, Alyssa/0000-0002-4235-4638 FU National Academy of Neuropsychology FX We acknowledge the following funding source: National Academy of Neuropsychology (PI: A. Thames). We also thank Ms. Myra Irani, Fredrica Hendrix, and Natalie Arbid for their assistance with data collection. The authors report no conflicts of interest. NR 60 TC 10 Z9 10 U1 5 U2 28 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2013 VL 19 IS 5 BP 583 EP 593 DI 10.1017/S1355617713000076 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 136OB UT WOS:000318370100010 PM 23388089 ER PT J AU Ausiello, DA Al-Awqati, Q AF Ausiello, Dennis A. Al-Awqati, Qais TI Alexander Leaf: in memoriam SO KIDNEY INTERNATIONAL LA English DT Biographical-Item ID TISSUES C1 [Ausiello, Dennis A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Al-Awqati, Qais] Columbia Univ, Dept Med, New York, NY USA. RP Ausiello, DA (reprint author), Massachusetts Gen Hosp, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM dausiello@partners.org NR 5 TC 0 Z9 0 U1 0 U2 2 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 MAY PY 2013 VL 83 IS 5 BP 771 EP 772 DI 10.1038/ki.2013.87 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 136EI UT WOS:000318344000001 ER PT J AU Zeng, C Giantsoudi, D Grassberger, C Goldberg, S Niemierko, A Paganetti, H Efstathiou, JA Trofimov, A AF Zeng, Chuan Giantsoudi, Drosoula Grassberger, Clemens Goldberg, Saveli Niemierko, Andrzej Paganetti, Harald Efstathiou, Jason A. Trofimov, Alexei TI Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions SO MEDICAL PHYSICS LA English DT Article DE intensity-modulated proton therapy; biological optimization; fractionation; therapeutic ratio ID PROSTATE-CANCER; RADIOTHERAPY; THERAPY; HYPOFRACTIONATION; TISSUE; SETUP AB Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled. (c) 2013 American Association of Physicists in Medicine. C1 [Zeng, Chuan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zeng, C (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM Zeng.Chuan@mgh.harvard.edu RI Zeng, Chuan/K-5694-2012 OI Zeng, Chuan/0000-0001-7069-2629 FU Federal Share of program income earned by Massachusetts General Hospital on Proton Therapy Research and Treatment Center [C06 CA059267] FX This study was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 24 TC 7 Z9 7 U1 1 U2 13 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 MAY PY 2013 VL 40 IS 5 AR 051708 DI 10.1118/1.4801897 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 139AO UT WOS:000318553900011 PM 23635256 ER PT J AU Ravegnini, G Marino-Enriquez, A Slater, J Eilers, G Wang, YX Zhu, MJ Nucci, MR George, S Angelini, S Raut, CP Fletcher, JA AF Ravegnini, Gloria Marino-Enriquez, Adrian Slater, Jaime Eilers, Grant Wang, Yuexiang Zhu, Meijun Nucci, Marisa R. George, Suzanne Angelini, Sabrina Raut, Chandrajit P. Fletcher, Jonathan A. TI MED12 mutations in leiomyosarcoma and extrauterine leiomyoma SO MODERN PATHOLOGY LA English DT Article DE fibroid; leiomyoma; leiomyosarcoma; MED12; oncogene; smooth muscle tumor; uterus ID OPITZ-KAVEGGIA-SYNDROME; UTERINE LEIOMYOSARCOMAS; FIBROIDS; MEDIATOR; SARCOMAS; TUMORS; AREAS; CDK8 AB Leiomyoma and leiomyosarcoma share morphological features and smooth muscle differentiation, and both arise most frequently within the uterine corpus of middle-aged women. However, they are considered biologically unrelated tumors due to their disparate clinical, cytogenetic, and molecular features. MED12, the mediator complex subunit 12 gene, has been recently implicated as an oncogene in as many as 70% of sporadic uterine leiomyoma. In the present study, we show MED12 hotspot exon 2 mutations in extrauterine leiomyoma (3 of 19 cases) and in leiomyosarcoma (3 of 13 uterine cases). We also show that MED12 mutations are found in both primary and metastatic leiomyosarcoma. Immunoblotting studies demonstrated MED12 protein expression in 100% of leiomyomas (13) and leiomyosarcomas (20), irrespective of MED12 exon 2 mutation status or histological grade. These findings indicate that MED12 has oncogenic roles in a broad range of smooth muscle neoplasia, including tumors arising in extrauterine locations. C1 [Ravegnini, Gloria; Marino-Enriquez, Adrian; Slater, Jaime; Eilers, Grant; Wang, Yuexiang; Zhu, Meijun; Nucci, Marisa R.; Fletcher, Jonathan A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ravegnini, Gloria; Angelini, Sabrina] Univ Bologna, Dept Pharmacol, Bologna, Italy. [George, Suzanne; Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jfletcher@partners.org RI RAVEGNINI, GLORIA/K-1330-2016; OI RAVEGNINI, GLORIA/0000-0002-7774-402X; Angelini, Sabrina/0000-0002-1609-0421 FU Daniel K. Ludwig Trust for Cancer Research; Sarcoma Alliance for Research Through Collaboration (SARC) Career Development Award; Department of Pharmacology, Universita di Bologna; Italian Society of Pharmacology; Fondazione del Monte di Bologna e Ravenna FX This study was supported by funding from the Daniel K. Ludwig Trust for Cancer Research (GR, AM-E, JS, GE, YW, MZ, and JF); a Sarcoma Alliance for Research Through Collaboration (SARC) Career Development Award (AM-E); and by the Department of Pharmacology, Universita di Bologna, Italian Society of Pharmacology, and Fondazione del Monte di Bologna e Ravenna (all to GR). NR 29 TC 29 Z9 30 U1 0 U2 3 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 MAY PY 2013 VL 26 IS 5 BP 743 EP 749 DI 10.1038/modpathol.2012.203 PG 7 WC Pathology SC Pathology GA 137RX UT WOS:000318456200014 PM 23222489 ER PT J AU Zhu, SM Nagashima, M Khan, MAS Yasuhara, S Kaneki, M Martyn, JAJ AF Zhu, Shimei Nagashima, Michio Khan, Mohammed A. S. Yasuhara, Shingo Kaneki, Masao Martyn, J. A. Jeevendra TI Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation SO MUSCLE & NERVE LA English DT Article DE apoptosis; caspase-3; immobilization; inflammation; skeletal muscle ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN SKELETAL-MUSCLE; UBIQUITIN-PROTEASOME; FIBER SIZE; PATHWAYS; DYSFUNCTION; ACTIVATION; EXPRESSION; PURIFICATION; CONTRIBUTES AB Introduction: Immobilization by casting induces disuse muscle atrophy (DMA). Methods: Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis, and inflammation during DMA. Results: Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 +/- 1% in KO vs. 41 +/- 3% in WT; soleus: 47 +/- 2% in KO vs. 56 +/- 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 +/- 4% in KO vs. 36 +/- 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius. Conclusions: Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways. Muscle Nerve 47: 711721, 2013 C1 [Martyn, J. A. Jeevendra] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Martyn, JAJ (reprint author), Shriners Hosp Children, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Room 206,51 Blossom St, Boston, MA USA. EM jmartyn@partners.org OI Nagashima, Michio/0000-0001-7416-5367 FU National Institutes of Health [RO1-055085, P50-25000]; Shriners Hospitals for Children FX Supported by grants from the National Institutes of Health (RO1-055085, P50-25000 project IV) and from Shriners Hospitals for Children to J. A. Jeevendra Martyn. We thank Dr. Hui Zheng for his advice on statistical analyses. NR 45 TC 18 Z9 19 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAY PY 2013 VL 47 IS 5 BP 711 EP 721 DI 10.1002/mus.23642 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 134SH UT WOS:000318234200012 PM 23401051 ER PT J AU Cohen-Adad, J Zhao, W Keil, B Ratai, EM Triantafyllou, C Lawson, R Dheel, C Wald, LL Rosen, BR Cudkowicz, M Atassi, N AF Cohen-Adad, Julien Zhao, Wei Keil, Boris Ratai, Eva-Maria Triantafyllou, Christina Lawson, Robert Dheel, Christina Wald, Lawrence L. Rosen, Bruce R. Cudkowicz, Merit Atassi, Nazem TI 7-T MRI of the spinal cord can detect lateral corticospinal tract abnormality in amyotrophic lateral sclerosis SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; corticospinal; MRI; spinal cord; ultra-high field ID MOTOR-NEURON DEGENERATION; ALS; BRAIN; CONTRAST; HYPERINTENSITY; DISEASE AB Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting lower and upper motor neurons. Degeneration of the lateral corticospinal tract (CST) is a key finding in ALS cervical spinal cord autopsies. We hypothesized that in vivo ultra-high-field MRI of the cervical spinal cord can detect abnormality in the CST. Methods: A patient with ALS (disease duration 23 months) and a healthy control were scanned at 7-T MRI using a 19-channel coil. Multi-echo T2*-weighted imaging was performed in the spinal cord, covering C2C6. Cross-sectional resolution was 0.37 x 0.37 mm2. Results: We detected clear signal hyperintensity in both segments of the lateral CST in the ALS patient, which was significant when compared with the normal control subject (P < 107). Conclusion: We believe there are potential benefits of 7-T MRI for increased sensitivity and spatial accuracy in characterizing pathology in the spinal cord. Muscle Nerve 47: 760762, 2013 C1 [Cohen-Adad, Julien; Zhao, Wei; Keil, Boris; Ratai, Eva-Maria; Triantafyllou, Christina; Lawson, Robert; Dheel, Christina; Wald, Lawrence L.; Rosen, Bruce R.; Cudkowicz, Merit; Atassi, Nazem] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cohen-Adad, Julien; Zhao, Wei; Keil, Boris; Ratai, Eva-Maria; Wald, Lawrence L.; Rosen, Bruce R.; Cudkowicz, Merit; Atassi, Nazem] Harvard Univ, Sch Med, Boston, MA USA. [Cohen-Adad, Julien] Ecole Polytech, Dept Elect Engn, Montreal, PQ H3C 3A7, Canada. [Triantafyllou, Christina] MIT, McGovern Inst Brain Res, AA Martinos Imaging Ctr, Cambridge, MA 02139 USA. [Lawson, Robert; Dheel, Christina; Cudkowicz, Merit; Atassi, Nazem] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Charlestown, MA USA. [Wald, Lawrence L.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Cohen-Adad, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM jcohen@polymtl.ca RI Keil, Boris/P-1411-2014; Wald, Lawrence/D-4151-2009 FU National Multiple Sclerosis Society [FG 1892A1/1]; National Center for Research Resources [P41-RR14075]; Harvard NeuroDiscovery Center; American Academy of Neurology; Muscular Dystrophy Association FX Supported by the National Multiple Sclerosis Society (FG 1892A1/1), the National Center for Research Resources (P41-RR14075), a pilot grant from the Harvard NeuroDiscovery Center, a fellowship grant from the American Academy of Neurology, and a training grant from the Muscular Dystrophy Association. NR 21 TC 9 Z9 9 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAY PY 2013 VL 47 IS 5 BP 760 EP 762 DI 10.1002/mus.23720 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 134SH UT WOS:000318234200017 PM 23553571 ER PT J AU Healy, BC Schoenfeld, D AF Healy, Brian C. Schoenfeld, David TI Can the combination of ALSFRS and survival time analysis impact the outcome in phase III ALS clinical trials? SO MUSCLE & NERVE LA English DT Letter ID AMYOTROPHIC-LATERAL-SCLEROSIS; PREDICTORS C1 [Healy, Brian C.; Schoenfeld, David] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Healy, Brian C.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Brookline, MA USA. [Schoenfeld, David] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Healy, BC (reprint author), Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAY PY 2013 VL 47 IS 5 BP 779 EP 780 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 134SH UT WOS:000318234200026 PM 23536327 ER PT J AU Wright, GD Hung, DT Helmann, JD AF Wright, Gerard D. Hung, Deborah T. Helmann, John D. TI How antibiotics kill bacteria: new models needed? SO NATURE MEDICINE LA English DT Editorial Material ID CELL-DEATH C1 [Wright, Gerard D.] McMaster Univ, MG DeGroote Inst Infect Dis Res, Hamilton, ON, Canada. [Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Hung, Deborah T.] Broad Inst MIT & Harvard, Program Infect Dis, Boston, MA USA. [Helmann, John D.] Cornell Univ, Dept Microbiol, New York, NY 10021 USA. RP Wright, GD (reprint author), McMaster Univ, MG DeGroote Inst Infect Dis Res, Hamilton, ON, Canada. OI Wright, Gerard/0000-0002-9129-7131; Helmann, John/0000-0002-3832-3249 FU NIGMS NIH HHS [R01 GM047446] NR 7 TC 7 Z9 7 U1 4 U2 49 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 MAY PY 2013 VL 19 IS 5 BP 544 EP 545 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 139LA UT WOS:000318583000025 PM 23652106 ER PT J AU Cypess, AM White, AP Vemochet, C Schulz, TJ Xue, RD Sass, CA Huang, TL Roberts-Toler, C Weiner, LS Sze, C Chacko, AT Deschamps, LN Herder, LM Truchan, N Glasgow, AL Holman, AR Gavrila, A Hasselgren, PO Mori, MA Molla, M Tseng, YH AF Cypess, Aaron M. White, Andrew P. Vemochet, Cecile Schulz, Tim J. Xue, Ruidan Sass, Christina A. Huang, Tian Liang Roberts-Toler, Carla Weiner, Lauren S. Sze, Cathy Chacko, Aron T. Deschamps, Laura N. Herder, Lindsay M. Truchan, Nathan Glasgow, Allison L. Holman, Ashley R. Gavrila, Alina Hasselgren, Per-Olof Mori, Marcelo A. Molla, Michael Tseng, Yu-Hua TI Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat SO NATURE MEDICINE LA English DT Article ID ADIPOSE-TISSUE; NONSHIVERING THERMOGENESIS; ADIPOCYTES; COLD; DISTINCT; IDENTIFICATION; CELL; PROGENITORS; ACTIVATION; SIGNATURES AB The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1)(1,2). BAT was once thought to have a functional role in rodents and human infants only, but it has been recently shown that in response to mild cold exposure, adult human BAT consumes more glucose per gram than any other tissue(3). In addition to this nonshivering thermogenesis, human BAT may also combat weight gain by becoming more active in the setting of increased whole-body energy intake(4-7). This phenomenon of BAT-mediated diet-induced thermogenesis has been observed in rodents(8) and suggests that activation of human BAT could be used as a safe treatment for obesity and metabolic dysregulation(9). In this study, we isolated anatomically defined neck fat from adult human volunteers and compared its gene expression, differentiation capacity and basal oxygen consumption to different mouse adipose depots. Although the properties of human neck fat vary substantially between individuals, some human samples share many similarities with classical, also called constitutive, rodent BAT. C1 [Cypess, Aaron M.; Vemochet, Cecile; Schulz, Tim J.; Xue, Ruidan; Sass, Christina A.; Huang, Tian Liang; Roberts-Toler, Carla; Weiner, Lauren S.; Sze, Cathy; Truchan, Nathan; Holman, Ashley R.; Mori, Marcelo A.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. [White, Andrew P.; Chacko, Aron T.; Deschamps, Laura N.; Herder, Lindsay M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthopaed Surg, Boston, MA 02215 USA. [Glasgow, Allison L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Harvard Thorndike Clin Res Ctr, Sch Med, Boston, MA 02215 USA. [Gavrila, Alina] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Endocrinol, Boston, MA 02215 USA. [Hasselgren, Per-Olof] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. [Molla, Michael] Harvard Univ, Sch Med, Joslin Diabet Ctr, Bioinformat Core,Res Div, Boston, MA 02115 USA. RP Cypess, AM (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab,Res Div, Boston, MA 02115 USA. EM aaron.cypess@joslin.harvard.edu RI Schulz, Tim/F-4842-2013 OI Schulz, Tim/0000-0002-8413-3972 FU US National Institutes of Health (NIH) from the National Institute of Diabetes and Digestive and Kidney Diseases [DK087317, DK081604, DK046200, DK077097, P30 DK036836, KL2 RR025757]; National Center for Research Resources, Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH) [UL1RR025758, UL1 RR 025758]; Harvard University; Harvard Stem Cell Institute; Eli Lilly Foundation FX This work was supported by US National Institutes of Health (NIH) grants DK087317, DK081604, DK046200, DK077097 and P30 DK036836 from the National Institute of Diabetes and Digestive and Kidney Diseases KL2 RR025757 and the Clinical Translational Science Award UL1RR025758 to Harvard University and Beth Israel Deaconess Medical Center from the National Center for Research Resources, Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers), as well as the Harvard Stem Cell Institute and Eli Lilly Foundation. We thank Y.I. Chen and K.K. Kwong for the magnetic resonance imaging; K. Chaudhary for assistance in figure design; M. Mittleman, H. Keenan and E. Wilker for biostatistical advice; J. Skupien for advice on factor analysis; H. Sacks for insights into the role of brown fat in warming blood; C. Cahill at the Joslin Diabetes Center Microscopy Core for expertise in histology; M. Rourk and G. Smyth for assistance in conducting the rodent studies; the teams of operating room nurses for assistance in tissue collection; and C.R. Kahn for input in preparing this manuscript. Finally, we are grateful to our volunteers for their commitment to the studies. NR 31 TC 218 Z9 220 U1 10 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 MAY PY 2013 VL 19 IS 5 BP 635 EP 639 DI 10.1038/nm.3112 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 139LA UT WOS:000318583000038 PM 23603815 ER PT J AU Song, JJ Guyette, JP Gilpin, SE Gonzalez, G Vacanti, JP Ott, HC AF Song, Jeremy J. Guyette, Jacques P. Gilpin, Sarah E. Gonzalez, Gabriel Vacanti, Joseph P. Ott, Harald C. TI Regeneration and experimental orthotopic transplantation of a bioengineered kidney SO NATURE MEDICINE LA English DT Article ID DECELLULARIZED MATRIX; BASEMENT-MEMBRANE; ARTIFICIAL-KIDNEY; PORCINE KIDNEYS; RENAL-FUNCTION; CELLS; REPLACEMENT; PODOCYTES; SCAFFOLDS; ADHESION AB Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo. C1 [Song, Jeremy J.; Guyette, Jacques P.; Gilpin, Sarah E.; Gonzalez, Gabriel; Vacanti, Joseph P.; Ott, Harald C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Song, Jeremy J.; Guyette, Jacques P.; Gilpin, Sarah E.; Gonzalez, Gabriel; Vacanti, Joseph P.; Ott, Harald C.] Harvard Univ, Sch Med, Boston, MA USA. [Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Div Pediat Surg, Boston, MA 02114 USA. [Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. RP Ott, HC (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM hott@partners.org FU US National Institutes of Health (NIH) [DP2 OD008749-01]; AOmegaA Research Fellowship; American Heart Association; NIH [DK43351, DK57521] FX The present study was supported by the US National Institutes of Health (NIH) Director's New Innovator Award DP2 OD008749-01 and departmental funds. J.J.S. was supported by an A Omega A Research Fellowship and an American Heart Association Predoctoral Fellowship. The Program in Membrane Biology Microscopy Core is supported by NIH grants DK43351 and DK57521. We further thank Q.C. Ott for critical review and editing of the manuscript. We thank C. Hoffman, J. Beagle and M. Duggan for technical support with urine sample analysis. We thank M. McKee for her expert support with transmission electron microscopy and A. Tisdale for her expert support with scanning electron microscopy. NR 31 TC 215 Z9 228 U1 14 U2 150 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 MAY PY 2013 VL 19 IS 5 BP 646 EP 651 DI 10.1038/nm.3154 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 139LA UT WOS:000318583000040 PM 23584091 ER PT J AU EL Andaloussi, S Maeger, I Breakefield, XO Wood, MJA AF EL Andaloussi, Samir Maeger, Imre Breakefield, Xandra O. Wood, Matthew J. A. TI Extracellular vesicles: biology and emerging therapeutic opportunities SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID TUMOR-DERIVED MICROVESICLES; MESENCHYMAL STEM-CELL; CALCIUM-DEPENDENT MANNER; DENDRITIC CELLS; MEMBRANE-VESICLES; PROGENITOR CELLS; MESSENGER-RNA; MULTIVESICULAR BODIES; HORIZONTAL TRANSFER; ENDOTHELIAL-CELLS AB Within the past decade, extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells in both prokaryotes and higher eukaryotes to regulate a diverse range of biological processes. In addition, pathophysiological roles for extracellular vesicles are beginning to be recognized in diseases including cancer, infectious diseases and neurodegenerative disorders, highlighting potential novel targets for therapeutic intervention. Moreover, both unmodified and engineered extracellular vesicles are likely to have applications in macro-molecular drug delivery. Here, we review recent progress in understanding extracellular vesicle biology and the role of extracellular vesicles in disease, discuss emerging therapeutic opportunities and consider the associated challenges. C1 [EL Andaloussi, Samir; Maeger, Imre; Wood, Matthew J. A.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Neurogenet Unit, Charlestown, MA USA. [EL Andaloussi, Samir] Karolinska Inst, Dept Lab Med, SE-14186 Solna, Sweden. [Maeger, Imre] Univ Tartu, Inst Technol, EE-50411 Tartu, Estonia. RP Wood, MJA (reprint author), Univ Oxford, Dept Physiol Anat & Genet, S Parks Rd, Oxford OX1 3QX, England. EM matthew.wood@dpag.ox.ac.uk OI Mager, Imre/0000-0003-2242-7227 FU Swedish Society of Medical Research (SSMF); Swedish Medical Research Council (VR-med unga forskare); Estonian Science Foundation FX S.E.A. is supported by a postdoctoral research fellowship from the Swedish Society of Medical Research (SSMF) and the Swedish Medical Research Council (VR-med unga forskare). I. M. is supported by a Postdoctoral MOBILITAS Fellowship of the Estonian Science Foundation. NR 120 TC 249 Z9 251 U1 24 U2 170 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD MAY PY 2013 VL 12 IS 5 BP 348 EP 358 DI 10.1038/nrd3978 PG 11 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 136GR UT WOS:000318350900013 PM 23584393 ER PT J AU Tepper, PG Randolph, JF McConnell, DS Crawford, SL El Khoudary, SR Joffe, H Gold, EB Zheng, HY Bromberger, JT Sutton-Tyrrell, K AF Tepper, Ping G. Randolph, John F., Jr. McConnell, Daniel S. Crawford, Sybil L. El Khoudary, Samar R. Joffe, Hadine Gold, Ellen B. Zheng, Huiyong Bromberger, Joyce T. Sutton-Tyrrell, Kim TI Trajectory Clustering of Estradiol and Follicle-Stimulating Hormone During the Menopausal Transition Among Women in the Study of Women's Health Across the Nation (SWAN) EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Tepper, Ping G.; El Khoudary, Samar R.; Sutton-Tyrrell, Kim] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Bromberger, Joyce T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol & Psychiat, Pittsburgh, PA USA. [Randolph, John F., Jr.] Univ Michigan, Sch Publ Hlth, Div Reprod Endocrinol & Infertil, Ann Arbor, MI 48109 USA. [McConnell, Daniel S.; Zheng, Huiyong] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Crawford, Sybil L.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth, Boston, MA USA. [Gold, Ellen B.] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. RP Tepper, PG (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2013 VL 68 IS 5 BP 361 EP 363 DI 10.1097/01.ogx.0000430387.83358.89 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 138BD UT WOS:000318482300017 ER PT J AU Wong, JR Harris, JK Rodriguez-Galindo, C Johnson, KJ AF Wong, Jeannette R. Harris, Jenine K. Rodriguez-Galindo, Carlos Johnson, Kimberly J. TI Incidence of Childhood and Adolescent Melanoma in the United States: 1973-2009 SO PEDIATRICS LA English DT Article DE melanoma; childhood; adolescence; incidence; SEER; trends; UV; cancer; epidemiology ID CUTANEOUS MALIGNANT-MELANOMA; ULTRAVIOLET-LIGHT EXPOSURE; INDOOR TANNING FACILITIES; LYMPH-NODE BIOPSY; SKIN-CANCER; XERODERMA-PIGMENTOSUM; POPULAR ATTITUDES; YOUNG-ADULTS; INVASIVE MELANOMA; MELANOCYTIC NEVI AB OBJECTIVE: Childhood and adolescent melanoma is rare but has been increasing. To gain insight into possible reasons underlying this observation, we analyzed trends in melanoma incidence diagnosed between the ages of 0 and 19 years among US whites by gender, stage, age at diagnosis, and primary site. We also investigated incidence trends by UV-B exposure levels. METHODS: By using Surveillance, Epidemiology, and End Results (SEER) program data (1973-2009), we calculated age-adjusted incidence rates (IRs), annual percent changes, and 95% confidence intervals for each category of interest. Incidence trends were also evaluated by using joinpoint and local regression models. SEER registries were categorized with respect to low or high UV-B radiation exposure. RESULTS: From 1973 through 2009, 1230 children of white race were diagnosed with malignant melanoma. Overall, pediatric melanoma increased by an average of 2% per year (95% confidence interval, 1.4%-2.7%). Girls, 15- to 19-year-olds, and individuals with low UV-B exposure had significantly higher IRs than boys, younger children, and those living in SEER registries categorized as high UV-B. Over the study period, boys experienced increased IRs for melanoma on the face and trunk, and females on the lower limbs and hip. The only decreased incidence trend we observed was among 15- to 19-year-olds in the high UV-B exposure group from 1985 through 2009. Local regression curves indicated similar patterns. CONCLUSIONS: These results may help elucidate possible risk factors for adolescent melanoma, but additional individual-level studies will be necessary to determine the reasons for increasing incidence trends. C1 [Wong, Jeannette R.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Harris, Jenine K.; Johnson, Kimberly J.] Washington Univ, Brown Sch, St Louis, MO USA. [Johnson, Kimberly J.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Rodriguez-Galindo, Carlos] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Johnson, KJ (reprint author), Washington Univ, 237 Goldfarb Hall,Campus Box 1196,1 Brookings Dr, St Louis, MO 63130 USA. EM kijohnson@brownschool.wustl.edu FU National Institutes of Health; National Cancer Institute; National Institutes of Health (NIH) FX Supported in part by the intramural research program of the National Institutes of Health and the National Cancer Institute. Funded by the National Institutes of Health (NIH). NR 64 TC 49 Z9 53 U1 0 U2 20 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2013 VL 131 IS 5 BP 846 EP 854 DI 10.1542/peds.2012-2520 PG 9 WC Pediatrics SC Pediatrics GA 135EO UT WOS:000318270700046 PM 23589817 ER PT J AU Rose, O Blanco, E Martinez, SM Sim, EK Castillo, M Lozoff, B Vaucher, YE Gahagan, S AF Rose, Olga Blanco, Estela Martinez, Suzanna M. Sim, Eastern Kang Castillo, Marcela Lozoff, Betsy Vaucher, Yvonne E. Gahagan, Sheila TI Developmental Scores at 1 Year With Increasing Gestational Age, 37-41 Weeks SO PEDIATRICS LA English DT Article DE gestational age; term infants; development; cognition; Bayley Scales of Infant Development ID LOW-BIRTH-WEIGHT; LATE-PRETERM BIRTH; SOCIOECONOMIC-STATUS; PREDICTIVE-VALIDITY; INFANT DEVELOPMENT; COGNITIVE FUNCTION; EARLY-CHILDHOOD; SCHOOL-AGE; NEAR-TERM; OUTCOMES AB OBJECTIVE: To examine the relationship between gestational age and mental and psychomotor development scores in healthy infants born between 37 and 41 weeks. METHODS: The cohort included 1562 participants enrolled during infancy in an iron deficiency anemia preventive trial in Santiago, Chile. All participants were healthy, full-term (37-41 weeks) infants who weighed 3 kg or more at birth. Development at 12 months was assessed using the Bayley Scales of Infant Development. Using generalized linear modeling, we analyzed the association between gestational age and 1-year-old developmental status, taking into account potential confounders including birth weight percentile, gender, socioeconomic status, the home environment, iron status, and iron supplementation. RESULTS: For each additional week of gestation, the Mental Development Index increased by 0.8 points (95% confidence interval = 0.2-1.4), and the Psychomotor Development Index increased by 1.4 points (95% confidence interval = 0.6-2.1) controlling for birth weight percentile, gender, socioeconomic status, and home environment. CONCLUSIONS: In a large sample of healthy full-term infants, developmental scores obtained using the Bayley Scales of Infant Development at 12 months increased with gestational age (37-41 weeks). There is increasing evidence that birth at 39 to 41 weeks provides developmental advantages compared with birth at 37 to 38 weeks. Because cesarean deliveries and early-term inductions have increased to 40% of all births, consideration of ongoing brain development during the full-term period is an important medical and policy issue. C1 [Rose, Olga; Sim, Eastern Kang] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rose, Olga; Blanco, Estela; Martinez, Suzanna M.; Gahagan, Sheila] Univ Calif San Diego, Div Child Dev & Community Hlth, San Diego, CA 92103 USA. [Vaucher, Yvonne E.; Gahagan, Sheila] Univ Calif San Diego, Dept Pediat, Div Neonatol, San Diego, CA 92103 USA. [Castillo, Marcela] Univ Chile, Inst Nutr & Food Technol, Santiago, Chile. [Lozoff, Betsy] Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. [Lozoff, Betsy] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. RP Gahagan, S (reprint author), Univ Calif San Diego, Div Child Dev & Community Hlth, San Diego, CA 92103 USA. EM sgahagan@ucsd.edu RI BLANCO, ESTELA/A-2541-2014 OI BLANCO, ESTELA/0000-0002-6232-9210 FU National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development [R01HL088530, R01HD33487, R01HD14122]; National Institutes of Health (NIH) FX Supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Child Health and Human Development (grants R01HL088530, R01HD33487, principal investigator: Gahagan; grants R01HD14122 and R01HD33487, principal investigator: Lozoff). Funded by the National Institutes of Health (NIH). NR 51 TC 15 Z9 16 U1 3 U2 14 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 MAY PY 2013 VL 131 IS 5 BP E1475 EP E1481 DI 10.1542/peds.2012-3215 PG 7 WC Pediatrics SC Pediatrics GA 135EO UT WOS:000318270700012 PM 23589812 ER PT J AU Walsh, KE Roblin, DW Weingart, SN Houlahan, KE Degar, B Billett, A Keuker, C Biggins, C Li, J Wasilewski, K Mazor, KM AF Walsh, Kathleen E. Roblin, Douglas W. Weingart, Saul N. Houlahan, Kathleen E. Degar, Barbara Billett, Amy Keuker, Christopher Biggins, Colleen Li, Justin Wasilewski, Karen Mazor, Kathleen M. TI Medication Errors in the Home: A Multisite Study of Children With Cancer SO PEDIATRICS LA English DT Article DE antineoplastic agents; medical errors; medication errors; patient safety; pediatric cancer; quality improvement ID ADVERSE DRUG EVENTS; RANDOMIZED CONTROLLED-TRIAL; PEDIATRIC INPATIENTS; ADMINISTRATION ERRORS; HEALTH-LITERACY; CARE; PARENTS AB OBJECTIVE: As home medication use increases, medications previously managed by nurses are now managed by patients and their families. Our objective was to describe the types of errors occurring in the home medication management of children with cancer. METHODS: In a prospective observational study at 3 pediatric oncology clinics in the northeastern and southeastern United States, patients undergoing chemotherapy and their parents were recruited from November 2007 through April 2011. We reviewed medical records and checked prescription doses. A trained nurse visited the home, reviewed medication bottles, and observed administration. Two physicians independently made judgments regarding whether an error occurred and its severity. Overall rates of errors were weighted to account for clustering within sites. RESULTS: We reviewed 963 medications and observed 242 medication administrations in the homes of 92 patients. We found 72 medication errors. Four errors led to significant patient injury. An additional 40 errors had potential for injury: 2 were life-threatening, 13 were serious, and 25 were significant. Error rates varied between study sites (40-121 errors per 100 patients); the weighted overall rate was 70.2 errors per 100 patients (95% confidence interval [CI]: 58.9-81.6). The weighted rate of errors with injury was 3.6 (95% CI: 1.7-5.5) per 100 patients and with potential to injure the patient was 36.3 (95% CI: 29.3-43.3) per 100 patients. Nonchemotherapy medications were more often involved in an error than chemotherapy. CONCLUSIONS: Medication errors were common in this multisite study of outpatient pediatric cancer care. Rates of preventable medication-related injuries in this outpatient population were comparable or higher than those found in studies of hospitalized patients. C1 [Walsh, Kathleen E.; Keuker, Christopher] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01605 USA. [Mazor, Kathleen M.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Walsh, Kathleen E.; Biggins, Colleen; Mazor, Kathleen M.] Meyers Primary Care Inst, Worcester, MA USA. [Roblin, Douglas W.] Kaiser Permanente, Atlanta, GA USA. [Weingart, Saul N.; Houlahan, Kathleen E.; Degar, Barbara; Billett, Amy; Li, Justin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Houlahan, Kathleen E.; Degar, Barbara; Billett, Amy] Childrens Hosp, Boston, MA 02115 USA. [Wasilewski, Karen] Emory Med Sch, Atlanta, GA USA. RP Walsh, KE (reprint author), Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01605 USA. FU Robert Wood Johnson Physician Faculty Scholars award; Charles H. Hood Foundation; National Cancer Institute [CRN U19 CA 79689] FX Dr Walsh was supported by a Robert Wood Johnson Physician Faculty Scholars award. This work was also supported by the Charles H. Hood Foundation and the National Cancer Institute (CRN U19 CA 79689). NR 42 TC 19 Z9 20 U1 2 U2 19 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 MAY PY 2013 VL 131 IS 5 BP E1405 EP E1414 DI 10.1542/peds.2012-2434 PG 10 WC Pediatrics SC Pediatrics GA 135EO UT WOS:000318270700003 PM 23629608 ER PT J AU Palotie, A Kallela, M Anttila, V AF Palotie, Aarno Kallela, Mikko Anttila, Verneri TI Probing the Brain of Comorbidity SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; MIGRAINE C1 [Palotie, Aarno] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Palotie, Aarno; Anttila, Verneri] Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland. [Palotie, Aarno; Anttila, Verneri] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Kallela, Mikko] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki 00029, Finland. [Anttila, Verneri] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. RP Palotie, A (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. EM ap8@sanger.ac.uk OI Anttila, Verneri/0000-0002-0073-4675 NR 10 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 1 PY 2013 VL 5 IS 183 AR 183fs15 DI 10.1126/scitranslmed.3006229 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 137FM UT WOS:000318420900002 PM 23636091 ER PT J AU Chen, CC Walker, WA AF Chen, Chien-Chang Walker, W. Allan TI Probiotics and the mechanism of necrotizing enterocolitis SO SEMINARS IN PEDIATRIC SURGERY LA English DT Article DE Necrotizing enterocolitis; Probiotics; Intestinal host defense ID CITROBACTER-RODENTIUM COLITIS; BIRTH-WEIGHT INFANTS; LACTOBACILLUS-ACIDOPHILUS; BACTERIAL-COLONIZATION; PREMATURE-INFANTS; PRETERM INFANTS; HUMAN INTESTINE; BREAST-MILK; SUPPLEMENTATION; INFECTION AB Necrotizing enterocolitis (NEC) is a severe intestinal inflammatory disorder in newborns. Although the pathogenesis of NEC is not completely understood, we reviewed the literature and our previous studies to explore the mechanism of NEC and to evaluate the role for probiotics in this disease. NEC may be associated with an inappropriate innate immune and excessive inflammatory response of the immature intestine. Probiotics are widely used in promoting human health and adjunctive therapy of human disease. There are growing clinical trials and research studies that support a beneficial role for probiotics for NEC. We have reviewed the literature associated with the use of probiotics in NEC. (C) 2013 Elsevier Inc. All rights reserved. C1 [Chen, Chien-Chang] Chang Gung Mem Hosp, Dept Pediat, Div Gastroenterol, Tao Yuan, Taiwan. [Chen, Chien-Chang] Chang Gung Univ, Coll Med, Tao Yuan, Taiwan. [Walker, W. Allan] Harvard Univ, Sch Med, Div Nutr, Boston, MA USA. [Walker, W. Allan] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Walker, W. Allan] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp Children, Mucosal Immunol Lab, 114 16th St, Charlestown, MA 02129 USA. EM wwalker@partners.org NR 53 TC 3 Z9 3 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-8586 J9 SEMIN PEDIATR SURG JI Semin. Pediatr. Surg. PD MAY PY 2013 VL 22 IS 2 BP 94 EP 100 DI 10.1053/j.sempedsurg.2013.01.0.06 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 137WG UT WOS:000318468300006 PM 23611613 ER PT J AU Kuna, ST Reboussin, DM Borradaile, KE Sanders, MH Millman, RP Zammit, G Newman, AB Wadden, TA Jakicic, JM Wing, RR Pi-Sunyer, FX Foster, GD AF Kuna, Samuel T. Reboussin, David M. Borradaile, Kelley E. Sanders, Mark H. Millman, Richard P. Zammit, Gary Newman, Anne B. Wadden, Thomas A. Jakicic, John M. Wing, Rena R. Pi-Sunyer, F. Xavier Foster, Gary D. CA Look AHEAD Res Grp TI Long-Term Effect of Weight Loss on Obstructive Sleep Apnea Severity in Obese Patients with Type 2 Diabetes SO SLEEP LA English DT Article DE Apnea-hypopnea index; polysomnogram ID RANDOMIZED CONTROLLED-TRIAL; LIFE-STYLE INTERVENTION; POSITIVE AIRWAY PRESSURE; LOW ENERGY DIET; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; HEART HEALTH; RISK-FACTORS; FOLLOW-UP; EXERCISE AB Study Objectives: To examine whether the initial benefit of weight loss on obstructive sleep apnea (OSA) severity at 1 year is maintained at 4 years. Design: Randomized controlled trial with follow-up at 1, 2, and 4 years. Setting: 4 Look AHEAD clinical centers. Participants: Two hundred sixty-four obese adults with type 2 diabetes and OSA. Interventions: Intensive lifestyle intervention with a behavioral weight loss program or diabetes support and education. Measurements: Change in apnea-hypopnea index on polysomnogram. Results: The intensive lifestyle intervention group's mean weight loss was 10.7 +/- 0.7 (standard error), 7.4 +/- 0.7, and 5.2 +/- 0.7 kg at 1, 2, and 4 years respectively, compared to a less than 1-kg weight loss for the control group at each time (P < 0.001). Apnea-hypopnea index difference between groups was 9.7 +/- 2.0, 8.0 +/- 2.0, and 7.7 +/- 2.3 events/h at 1, 2 and 4 years respectively (P < 0.001). Change in apnea-hypopnea index over time was related to the amount of weight loss (P < 0.0001) and intervention, independent of weight loss (P = 0.001). Remission of OSA at 4 years was 5 times more common with intensive lifestyle intervention (20.7%) than diabetes support and education (3.6%). Conclusions: Among obese adults with type 2 diabetes and OSA, intensive lifestyle intervention produced greater reductions in weight and apnea-hypopnea index over a 4 year period than did diabetes support and education. Beneficial effects of intensive lifestyle intervention on apnea-hypopnea index at 1 year persisted at 4 years, despite an almost 50% weight regain. Effect of intensive lifestyle intervention on apnea-hypopnea index was largely, but not entirely, due to weight loss. C1 [Kuna, Samuel T.; Wadden, Thomas A.] Univ Penn, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Reboussin, David M.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Borradaile, Kelley E.; Foster, Gary D.] Temple Univ, Philadelphia, PA 19122 USA. [Sanders, Mark H.; Newman, Anne B.; Jakicic, John M.] Univ Pittsburgh, Pittsburgh, PA USA. [Millman, Richard P.; Wing, Rena R.] Brown Univ, Providence, RI 02912 USA. [Zammit, Gary] Clinilabs, New York, NY USA. [Pi-Sunyer, F. Xavier] Columbia Univ, New York, NY USA. RP Kuna, ST (reprint author), Philadelphia VA Med Ctr 111P, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM skuna@mail.med.upenn.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institutes of Health NHLBI [HL070301]; National Institutes of Health NIDDK [DK60426, DK56992, DK057135]; NIH; CDC; USDA; Robert Wood Johnson Foundation; Nutrisystem American Beverage Association; Novo-Nordisk; JennyCraig; Philips Respironics; Abbott; Actelion; Ancile; Apnex; Arena; Aventis; Cephalon Inc; CHDI; Elan; Epic; Evotec; Forest; Galderma; Glaxo Smith Kline; H. Lundbeck A/S; King; Merck and Co.; National Institute of Health (NIH); Neurim; Neurocrine Biosciences; Neurogen; Organon; Orphan Medical; Otsuka; Pfizer; Predix; Respironics; Sanofi-Aventis; Sanofi-Synthelabo; Schering-Plough; Sepracor; Shire; Somaxon; Takeda Pharmaceuticals North America; Targacept; Thymon; Transcept; UCB Pharma; Vanda; Wyeth-Ayerst Research; NutriSystem FX This study was supported by the National Institutes of Health NHLBI grant HL070301 and NIDDK grants DK60426, DK56992, and DK057135; This was not an industry supported study. Dr. Foster serves on the Scientific Advisory Board of Con Agra Foods, Nutrisystem, Tate, Lyle and United Health Group. He has received grants from NIH, CDC, USDA, Robert Wood Johnson Foundation, Nutrisystem American Beverage Association and Novo-Nordisk. Dr. Jakicic is a member of Free & Clear Scientific Advisory Board, has grants or grants pending from BodyMedia, Inc., and receives payment for lectures by JennyCraig. Dr. Kuna receives grant support from Philips Respironics. Dr. Sanders is Editor-in-Chief and Editor for UpToDate (R); Field Editor for Sleep Medicine and Deputy Editor for the journal SLEEP. He serves as a consultant to Philips Respironics. Dr. Zammit is a consultant for Actelion, Alexza, Arena, Aventis, Biovail, Boehringer-Ingelheim, Cephalon, Elan, Eli Lilly, Evotec, Forest, Glaxo Smith Kline, Jazz Pharmaceuticals, King Pharmaceuticals, Ligand, McNeil, Merck, Neurocrine Biosciences, Organon, Pfizer, Renovis, Sanofi-Aventis, Select Comfort, Sepracor, Shire, Somnus, Takeda Pharmaceuticals, Vela, and Wyeth-Ayerst Research. He also provides expert testimony for Acorda and has received grants or has grants pending from Abbott, Actelion, Ancile, Apnex, Arena, Aventis, Cephalon Inc, CHDI, Elan, Epic, Evotec, Forest, Galderma, Glaxo Smith Kline, H. Lundbeck A/S, King, Merck and Co., National Institute of Health (NIH), Neurim, Neurocrine Biosciences, Neurogen, Organon, Orphan Medical, Otsuka, Pfizer, Predix, Respironics, Sanofi-Aventis, Sanofi-Synthelabo, Schering-Plough, Sepracor, Shire, Somaxon, Takeda Pharmaceuticals North America, Targacept, Thymon, Transcept, UCB Pharma, Predix, Vanda, and Wyeth-Ayerst Research. Dr. Zammit has received payment for lectures from Neurocrine Biosciences, King Pharmaceuticals, McNeil, Sanofi-Aventis, Sanofi-Synthelabo, Sepracor, Takeda Pharmaceuticals, Vela Pharmaceuticals, and Wyeth-Ayerst Research. Dr. Wadden has received grant support from NutriSystem and serves on the advisory boards of Novo Nordisk, Orexigen and Vivus. Dr. Millman has served as a consultant for Johnson and Johnson Business Development. The other authors have indicated no financial conflicts of interest. NR 41 TC 51 Z9 54 U1 1 U2 11 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 MAY 1 PY 2013 VL 36 IS 5 BP 641 EP 649 DI 10.5665/sleep.2618 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 137AL UT WOS:000318406600006 PM 23633746 ER PT J AU Zhang, XH Giovannucci, EL Wu, KN Gao, X Hu, F Ogino, S Schernhammer, ES Fuchs, CS Redline, S Willett, WC Ma, J AF Zhang, Xuehong Giovannucci, Edward L. Wu, Kana Gao, Xiang Hu, Frank Ogino, Shuji Schernhammer, Eva S. Fuchs, Charles S. Redline, Susan Willett, Walter C. Ma, Jing TI Associations of Self-Reported Sleep Duration and Snoring with Colorectal Cancer Risk in Men and Women SO SLEEP LA English DT Article DE Sleep duration; snoring; colorectal cancer; incidence; prospective study ID FOOD FREQUENCY QUESTIONNAIRE; INTERMITTENT HYPOXIA; BREAST-CANCER; WEIGHT-GAIN; METABOLIC SYNDROME; NURSES HEALTH; COLON-CANCER; MORTALITY; CORTISOL; COHORT AB Study Objectives: We assessed the relationship between sleep duration, snoring and colorectal cancer risk. Design: Prospective cohort studies. Setting: United States. Participants: A total of 30,121 men aged 41 to 79 years in the Health Professionals Follow-up Study and 76,368 women aged 40 to 73 years in the Nurses' Health Study. Interventions: None. Measurements and Results: We queried information on sleep duration and snoring in 1986/87. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs, 95% CIs). We documented 1,973 incident colorectal cancer cases (709 men and 1,264 women) over a 22-year follow-up period. Compared to sleep an average 7 h, >= 9 h of sleep was significantly associated with a higher risk of colorectal cancer among men (HR = 1.35, 95% CI: 1.00, 1.82), and to a lesser degree, among women (HR = 1.11, 95% CI: 0.85, 1.44). The risk associated with longer sleep was restricted to individuals who regularly snored (men: HR = 1.80, 95% CI: 1.14, 2.84; women: HR = 2.32, 95% CI: 1.24, 4.36) and to overweight individuals (i.e., BMI >= 25 kg/m(2)) (men: HR = 1.52, 95% CI: 1.04, 2.21; women: HR = 1.37, 95% CI: 0.97, 1.94). Short sleep duration (<= 5 h) was not associated with an increased risk of colorectal cancer in the entire sample or in subgroups stratified by snoring or BMI. Conclusions: Longer sleep duration was associated with an increased risk of developing colorectal cancer among individuals who were overweight or snored regularly. This observation raises the possibility that sleep apnea and its attendant intermittent hypoxemia may contribute to cancer risk. C1 [Zhang, Xuehong; Giovannucci, Edward L.; Gao, Xiang; Hu, Frank; Schernhammer, Eva S.; Fuchs, Charles S.; Willett, Walter C.; Ma, Jing] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Zhang, Xuehong; Giovannucci, Edward L.; Gao, Xiang; Hu, Frank; Ogino, Shuji; Schernhammer, Eva S.; Fuchs, Charles S.; Willett, Walter C.; Ma, Jing] Harvard Univ, Sch Med, Boston, MA USA. [Giovannucci, Edward L.; Wu, Kana; Gao, Xiang; Hu, Frank; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Hu, Frank; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA. [Redline, Susan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Zhang, XH (reprint author), 401 Pk Dr,Suite 301 West, Boston, MA 02115 USA. EM xuehong.zhang@channing.harvard.edu; jing.ma@channing.harvard.edu FU NIH [CA87969, 1U54CA155626-01, CA151993, CA55075] FX The authors thank the participants and staff of the NHS and HPFS 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. This study was funded by the NIH grants CA87969, 1U54CA155626-01, CA151993, and CA55075. NR 37 TC 28 Z9 29 U1 0 U2 14 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 MAY 1 PY 2013 VL 36 IS 5 BP 681 EP 688 DI 10.5665/sleep.2626 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 137AL UT WOS:000318406600010 PM 23633750 ER PT J AU Ma, ML Chiu, A Sahay, G Doloff, JC Dholakia, N Thakrar, R Cohen, J Vegas, A Chen, DL Bratlie, KM Dang, T York, RL Hollister-Lock, J Weir, GC Anderson, DG AF Ma, Minglin Chiu, Alan Sahay, Gaurav Doloff, Joshua C. Dholakia, Nimit Thakrar, Raj Cohen, Joshua Vegas, Arturo Chen, Delai Bratlie, Kaitlin M. Dang, Tram York, Roger L. Hollister-Lock, Jennifer Weir, Gordon C. Anderson, Daniel G. TI Core-Shell Hydrogel Microcapsules for Improved Islets Encapsulation SO ADVANCED HEALTHCARE MATERIALS LA English DT Article DE Islets encapsulation; transplantation; core-shell structures; immuno-protection; microcapsules; hydrogels ID TYPE-1 DIABETES-MELLITUS; ALGINATE MICROCAPSULES; PANCREATIC-ISLETS; PORCINE ISLETS; NONIMMUNOSUPPRESSED PATIENTS; GRAFT IMMUNOPROTECTION; IN-VITRO; CELLS; IMMUNOISOLATION; MICROENCAPSULATION C1 [Ma, Minglin; Chiu, Alan; Sahay, Gaurav; Doloff, Joshua C.; Dholakia, Nimit; Thakrar, Raj; Vegas, Arturo; Chen, Delai; Dang, Tram; York, Roger L.; Anderson, Daniel G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Anderson, Daniel G.] MIT, Div Hlth Sci Technol, Cambridge, MA 02139 USA. [Ma, Minglin; Chiu, Alan; Doloff, Joshua C.; Dholakia, Nimit; Thakrar, Raj; Vegas, Arturo; Chen, Delai; Dang, Tram; York, Roger L.; Anderson, Daniel G.] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Cohen, Joshua; Hollister-Lock, Jennifer; Weir, Gordon C.; Anderson, Daniel G.] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Div Res, Boston, MA 02215 USA. [Bratlie, Kaitlin M.] Iowa State Univ, Dept Mat Sci & Engn, Ames, IA 50011 USA. [Bratlie, Kaitlin M.] Iowa State Univ, Dept Chem & Biol Engn, Ames, IA 50011 USA. RP Anderson, DG (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dgander@mit.edu RI York, Roger/C-6547-2008; Dang, Tram/E-7966-2011 OI York, Roger/0000-0002-5105-6800; FU Juvenile Diabetes Research Foundation [17-2007-1063]; National Institutes of Health [F32 EB011580-01] FX This research was supported by the Juvenile Diabetes Research Foundation under grant 17-2007-1063, and a generous gift from the Tayebati Family Foundation. K. M. B. is grateful for support from the National Institutes of Health Postdoctoral Fellowship F32 EB011580-01. We are grateful to Miri Park, Thema Vietti, Justin Chin, Dr. Christian Kastrup and Dr. Shan Jiang for help and discussion. NR 48 TC 31 Z9 31 U1 4 U2 96 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD MAY PY 2013 VL 2 IS 5 BP 667 EP 672 DI 10.1002/adhm.201200341 PG 6 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA 135TU UT WOS:000318312200004 PM 23208618 ER PT J AU Estrella, MM Abraham, AG Jing, YZ Parekh, RS Tien, PC Merenstein, D Pearce, CL Anastos, K Cohen, MH Dehovitz, JA Gange, SJ AF Estrella, Michelle M. Abraham, Alison G. Jing, Yuezhou Parekh, Rulan S. Tien, Phyllis C. Merenstein, Dan Pearce, Celeste Leigh Anastos, Kathryn Cohen, Mardge H. Dehovitz, Jack A. Gange, Stephen J. TI Antiretroviral-Treated HIV-Infected Women Have Similar Long-Term Kidney Function Trajectories as HIV-Uninfected Women SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; INTERAGENCY HIV; RENAL-FUNCTION; TENOFOVIR; THERAPY; NEPHROPATHY; DISEASE; SAFETY; COHORT AB Natural history studies suggest increased risk for kidney function decline with HIV infection, but few studies have made comparisons with HIV-uninfected women. We examined whether HIV infection treated with highly active antiretroviral therapy (HAART) remains associated with faster kidney function decline in the Women's Interagency HIV Study. HIV-infected women initiating HAART with (n = 105) or without (n = 373) tenofovir (TDF) were matched to HIV-uninfected women on calendar and length of follow-up, age, systolic blood pressure, hepatitis C antibody serostatus, and diabetes history. Linear mixed models were used to evaluate differences in annual estimated glomerular filtration rate (eGFR). Person-visits were 4,741 and 11,512 for the TDF-treated and non-TDF-treated analyses, respectively. Mean baseline eGFRs were higher among women initiated on TDF-containing HAART and lower among those on TDF-sparing HAART compared to their respective HIV-uninfected matches (p < 0.05 for both). HIV-infected women had annual rates of eGFR changes similar to HIV-uninfected matches (p-interaction >0.05 for both). Adjusting for baseline eGFR, mean eGFRs at 1 and 3 years of follow-up among women initiated on TDF-containing HAART were lower than their uninfected matches (-4.98 and -4.26ml/min/1.73 m(2), respectively; p < 0.05 for both). Mean eGFR of women initiated on TDF-sparing HAART was lower versus uninfected matches at 5 years (-2.19ml/min/1.73 m(2), p = 0.03). HAART-treated HIV-infected women had lower mean eGFRs at follow-up but experienced rates of annual eGFR decline similar to HIV-uninfected women. Tenofovir use in HIV-infected women with normal kidney function did not accelerate long-term kidney function decline relative to HIV-uninfected women. C1 [Estrella, Michelle M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Abraham, Alison G.; Jing, Yuezhou; Parekh, Rulan S.; Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Parekh, Rulan S.] Univ Toronto, Div Nephrol, Toronto, ON, Canada. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Merenstein, Dan] Georgetown Univ, Med Ctr, Dept Family Med, Washington, DC 20007 USA. [Pearce, Celeste Leigh] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Anastos, Kathryn] Stroger Hosp, Montefiore Med Ctr, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Dehovitz, Jack A.] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. RP Estrella, MM (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, 1830 East Monument St,Suite 416, Baltimore, MD 21205 USA. EM mestrel1@jhmi.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI grant) [UL1 RR024131]; NIH-NIDDK grant [K23DK081317] FX Data in this article were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington, DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); and Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. M.M.E. is supported by NIH-NIDDK grant K23DK081317. NR 20 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 2013 VL 29 IS 5 BP 755 EP 760 DI 10.1089/aid.2012.0248 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 132NA UT WOS:000318074200003 PM 23273313 ER PT J AU Lahiff, C Cheifetz, AS AF Lahiff, C. Cheifetz, A. S. TI Commentary: irritable bowel syndrome and the CDAI misleading activity by straw men; authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID CROHNS-DISEASE C1 [Lahiff, C.; Cheifetz, A. S.] Beth Israel Deaconess Med Ctr & Harvard Med Sch, Ctr Inflammatory Bowel Dis, Boston, MA USA. RP Lahiff, C (reprint author), Beth Israel Deaconess Med Ctr & Harvard Med Sch, Ctr Inflammatory Bowel Dis, Boston, MA 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 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD MAY PY 2013 VL 37 IS 10 BP 1021 EP 1022 DI 10.1111/apt.12297 PG 2 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 131JT UT WOS:000317989900015 PM 23590539 ER PT J AU Lewandrowski, K Tamerius, J Menegus, M Olivo, PD Lollar, R Lee-Lewandrowski, E AF Lewandrowski, Kent Tamerius, John Menegus, Marilyn Olivo, Paul D. Lollar, Ron Lee-Lewandrowski, Elizabeth TI Detection of Influenza A and B Viruses With the Sofia Analyzer A Novel, Rapid Immunofluorescence-Based In Vitro Diagnostic Device SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Influenza virus; Rapid diagnostic test ID H1N1; METAANALYSIS; PERFORMANCE; INFECTION; TESTS; MANAGEMENT; THAILAND AB This report describes the clinical evaluation of a novel fluorescent immunoassay (FIA), Sofia Influenza A+B FIA (Quidel, San Diego, CA), for the rapid detection and differentiation of influenza A and B viruses. A total of 2,047 subjects provided nasal swabs and nasopharyngeal swabs or aspirates. The overall sensitivity and specificity for influenza A virus vs virus culture were 94% and 95%, respectively, and for influenza B virus were 89% and 96%, respectively. Fourteen hundred and sixty-one specimens were available for testing with reverse transcriptase polymerase chain reaction (RT-PCR). The sensitivity of the Sofia Influenza A+B FIA for detecting influenza A and B viruses compared with the RT-PCR method was 78% and 86%, respectively. A high percentage of the positive specimens had low cycle threshold values, and almost all of these were positive with the Sofia test. This high level of sensitivity demonstrates that the Sofia influenza A+B FIA could improve the usefulness of rapid influenza virus testing C1 [Lewandrowski, Kent; Lee-Lewandrowski, Elizabeth] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Tamerius, John; Olivo, Paul D.; Lollar, Ron] Quidel Corp, San Diego, CA USA. [Menegus, Marilyn] Univ Rochester, Med Ctr, Dept Clin Virol, Rochester, NY 14642 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM Elewandrowski@partners.org FU Quidel Corp. FX This study was supported by funding from Quidel Corp. NR 19 TC 19 Z9 19 U1 0 U2 13 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2013 VL 139 IS 5 BP 684 EP 689 DI 10.1309/AJCP7ZTLJCP3LLMA PG 6 WC Pathology SC Pathology GA 131MA UT WOS:000317996600014 PM 23596120 ER PT J AU Le, LP Garibyan, L Lara, D Finberg, KE Iafrate, AJ Duncan, LM Kay, J Nazarian, RM AF Le, Long P. Garibyan, Lilit Lara, Daniel Finberg, Karin E. Iafrate, A. John Duncan, Lyn M. Kay, Jonathan Nazarian, Rosalynn M. TI Fibrosis-Associated Single-Nucleotide Polymorphisms in TGFB1 and CAV1 Are Not Associated With the Development of Nephrogenic Systemic Fibrosis SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE nephrogenic systemic fibrosis; gadolinium; single-nucleotide polymorphism; caveolin-1; transforming growth factor-beta 1 ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1 GENE; RENAL-DISEASE; GADOLINIUM EXPOSURE; GRAFT FIBROSIS; LIVER FIBROSIS; HEPATITIS-C; SCLEROSIS; CAVEOLIN-1; PROGRESSION AB Objective: To test the hypothesis that the subset of patients with impaired renal function who are exposed to gadolinium-containing contrast agents (GCCAs) and develop nephrogenic systemic fibrosis (NSF) have a genetic predisposition for disease. Methods: We examined whether an intronic single-nucleotide polymorphism (SNP) in caveolin-1 (CAV1 rs4730751) and 2 coding SNPs in transforming growth factor-beta 1 (TGFB1 rs1800471, codon 25; and rs1800470, codon 10) were associated with the NSF phenotype. Results: Forty-one patients with a history of chronic kidney disease and GCCA administration were studied, including NSF cases (n = 17) and control subjects (n = 24) without clinical or histological evidence of NSF. No significant differences in the genotype frequencies at these SNPs in TGFB1 and CAV1 were found between patients with NSF and subjects without NSF. Conclusions: We conclude that polymorphisms in the genes encoding TGFB1 and CAV1 previously associated with the development and progression of fibrosis in several organ systems are not associated with development of NSF in this cohort of patients with renal impairment after GCCA exposure. C1 [Le, Long P.; Lara, Daniel; Iafrate, A. John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv,Diagnost Mol Pathol Lab, Boston, MA 02114 USA. [Garibyan, Lilit] Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02114 USA. [Finberg, Karin E.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Kay, Jonathan] Univ Massachusetts, Sch Med, Dept Med, Div Rheumatol,UMass Mem Med Ctr, Worcester, MA USA. [Duncan, Lyn M.; Nazarian, Rosalynn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit,Pathol Serv, Boston, MA 02114 USA. RP Nazarian, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit,Pathol Serv, 55 Fruit St,Warren 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193; Kay, Jonathan/0000-0002-8970-4260 FU Pathology Service at Massachusetts General Hospital FX Supported by the Austin L. Vickery, Jr. Translational Research Grant from the Pathology Service at Massachusetts General Hospital. NR 51 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD MAY PY 2013 VL 35 IS 3 BP 351 EP 356 DI 10.1097/DAD.0b013e31826c5508 PG 6 WC Dermatology SC Dermatology GA 130LP UT WOS:000317918800014 PM 23051628 ER PT J AU Bartnikas, T Steinbicker, A Campagna, D Blevins, S Woodward, L Herrera, C Bloch, K Justice, M Fleming, M AF Bartnikas, Tom Steinbicker, Andrea Campagna, Dean Blevins, Sherika Woodward, Lanette Herrera, Carolina Bloch, Kenneth Justice, Monica Fleming, Mark TI IDENTIFICATION AND CHARACTERIZATION OF A NOVEL MURINE ALLELE OF TMPRSS6 SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Bartnikas, Tom; Herrera, Carolina] Brown Univ, Providence, RI 02912 USA. [Steinbicker, Andrea] Univ Munster, Munster, Germany. [Campagna, Dean; Blevins, Sherika; Fleming, Mark] Boston Childrens Hosp, Boston, MA USA. [Woodward, Lanette; Justice, Monica] Baylor Coll Med, Houston, TX 77030 USA. [Bloch, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E59 EP E59 PG 1 WC Hematology SC Hematology GA 132BT UT WOS:000318043500093 ER PT J AU Duce, J Lei, P Tsatsanis, A Wong, B Lam, L Ayton, S Rogers, J Finkelstein, D Bush, A AF Duce, James Lei, Peng Tsatsanis, Andrew Wong, Bruce Lam, Linh Ayton, Scott Rogers, Jack Finkelstein, David Bush, Ashley TI A NOVEL RELATIONSHIP BETWEEN beta-AMYLOID PROTEIN PRECURSOR AND TAU IN ALZHEIMER'S DISEASE RELATED IRON DISRUPTION SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Duce, James; Tsatsanis, Andrew] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. [Rogers, Jack] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lei, Peng/F-6326-2010 OI Lei, Peng/0000-0001-5652-1962 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E34 EP E35 PG 2 WC Hematology SC Hematology GA 132BT UT WOS:000318043500051 ER PT J AU Metelo, A Xiang, L Baker, R Kamentsky, L Carpenter, A Peterson, R Iliopoulos, O AF Metelo, Ana Xiang, Li Baker, Rania Kamentsky, Lee Carpenter, Anne Peterson, Randall Iliopoulos, Othon TI SMALL MOLECULE HIF-2 alpha INHIBITORS SUPPRESS ERYTHROCYTOSIS AND PATHOLOGIC ANGIOGENESIS OF VHL -/- ZEBRAFISH SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Metelo, Ana; Xiang, Li; Baker, Rania; Peterson, Randall; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kamentsky, Lee; Carpenter, Anne] Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E25 EP E26 PG 2 WC Hematology SC Hematology GA 132BT UT WOS:000318043500034 ER PT J AU Meynard, D Sun, CC Chen, WJ Wu, QF Chen, SZ Nelson, CN Waters, MJ Babitt, JL Lin, HY AF Meynard, Delphine Sun, Chia Chi Chen, Wenjie Wu, Qifang Chen, Shanzhuo Nelson, Caroline. N. Waters, Michael. J. Babitt, Jodie. L. Lin, Herbert Y. TI INFLAMMATION REGULATES TMPRSS6 EXPRESSION VIA STAT5 IN HUMAN CELLS AND MICE SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Meynard, Delphine; Sun, Chia Chi; Chen, Wenjie; Wu, Qifang; Chen, Shanzhuo; Babitt, Jodie. L.; Lin, Herbert Y.] Massachusetts Gen Hosp, Program Anemia Signaling Res, Div Nephrol, Program Membrane Biol,Ctr Syst Biol, Boston, MA 02114 USA. [Meynard, Delphine; Sun, Chia Chi; Chen, Wenjie; Wu, Qifang; Chen, Shanzhuo; Babitt, Jodie. L.; Lin, Herbert Y.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nelson, Caroline. N.; Waters, Michael. J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. [Nelson, Caroline. N.; Waters, Michael. J.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia. RI Nelson, Caroline/H-4213-2013; meynard, delphine/B-4236-2014; waters, michael/C-9582-2014 NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E29 EP E30 PG 2 WC Hematology SC Hematology GA 132BT UT WOS:000318043500042 ER PT J AU Smith, A Hahl, P Davis, T Thakor, P Kaja, S Washburn, C Rogers, J AF Smith, Ann Hahl, Peter Davis, Taron Thakor, Preeti Kaja, Simon Washburn, Cecilia Rogers, Jack TI MODELING HEME, IRON AND COPPER HOMEOSTASIS IN BRAIN INJURY SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Smith, Ann] UMKC, Kansas City, MO USA. [Hahl, Peter; Davis, Taron; Thakor, Preeti] Univ Missouri, Sch Biol Sci, Kansas City, MO 64110 USA. [Kaja, Simon] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Washburn, Cecilia; Rogers, Jack] Massachusetts Gen Hosp, Psychiat Neurosci Dept, Boston, MA 02114 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E160 EP E160 PG 1 WC Hematology SC Hematology GA 132BT UT WOS:000318043500267 ER PT J AU Sun, CC Chen, WJ Gutierrez, O Pietrangelo, A Babitt, J Lin, H AF Sun, Chia Chi Chen, Wenjie Gutierrez, Orlando Pietrangelo, Antonello Babitt, Jodie Lin, Herbert TI A VALIDATED ELISA FOR QUANTITATING HUMAN SERUM HEMOJUVELIN SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Sun, Chia Chi; Chen, Wenjie; Babitt, Jodie; Lin, Herbert] Harvard Univ, Massachusetts Gen Hosp, Program Anemia Signaling Res, Div Nephrol,Program Membrane Biol,Med Sch, Boston, MA USA. [Gutierrez, Orlando] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Pietrangelo, Antonello] Univ Hosp Modena & Reggio Emilia, Mario Coppo Liver Res Ctr, Lab Hereditary & Metab Dis Liver, Modena, Italy. RI Pietrangelo, Antonello/K-1517-2016 OI Pietrangelo, Antonello/0000-0002-7411-935X 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E106 EP E107 PG 2 WC Hematology SC Hematology GA 132BT UT WOS:000318043500172 ER PT J AU Zumbrennen-Bullough, K Wu, QF Chen, WJ Babitt, J AF Zumbrennen-Bullough, Kimberly Wu, Qifang Chen, Wenjie Babitt, Jodie TI MICRORNA-130A DOWNREGULATES HEPCIDIN EXPRESSION DURING IRON DEFICIENCY BY TARGETING ALK2 SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Div Nephrol, Program Membrane Biol,Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E9 EP E9 PG 1 WC Hematology SC Hematology GA 132BT UT WOS:000318043500006 ER PT J AU Tramontano, AC Cipriano, LE Kong, CY Shepard, JAO Lanuti, M Gazelle, GS McMahon, PM AF Tramontano, Angela C. Cipriano, Lauren E. Kong, Chung Yin Shepard, Jo-Anne O. Lanuti, Michael Gazelle, G. Scott McMahon, Pamela M. TI Microsimulation Model Predicts Survival Benefit of Radiofrequency Ablation and Stereotactic Body Radiotherapy Versus Radiotherapy for Treating Inoperable Stage I Non-Small Cell Lung Cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE comparative effectiveness; lung cancer; radiofrequency ablation; stereotactic body radiotherapy ID RADIATION-THERAPY; NONSURGICAL CANDIDATES; UNITED-STATES; FOLLOW-UP; PHASE-II; TUMORS; EFFICACY; HEALTH; MIDTERM AB OBJECTIVE. A subset of patients with stage IA and IB non-small cell lung cancer (NSCLC) is ineligible for surgical resection and undergoes radiation therapy. Radiofrequency ablation (RFA) and stereotactic body radiotherapy are newer potentially attractive alternative therapies. MATERIALS AND METHODS. We added RFA and stereotactic body radiotherapy treatment modules to a microsimulation model that simulates lung cancer's natural history, detection, and treatment. Natural history parameters were previously estimated via calibration against tumor registry data and cohort studies; the model was validated with screening study and cohort data. RFA model parameters were calibrated against 2-year survival from the Radiofrequency Ablation of Pulmonary Tumor Response Evaluation (RAPTURE) study, and stereotactic body radiotherapy model parameters were calibrated against 3-year survival from a phase 2 prospective trial. We simulated lifetime histories of identical patients with early-stage NSCLC who were ineligible for resection, who were treated with radiation therapy, RFA, or stereotactic body radiotherapy under a range of scenarios. From 5,000,000 simulated individuals, we selected a cohort of patients with stage I medically inoperable cancer for analysis (n = 2056 per treatment scenario). Main outcomes were life expectancy gains. RESULTS. RFA or stereotactic body radiotherapy treatment in patients with peripheral stage IA or IB NSCLC who were nonoperative candidates resulted in life expectancy gains of 1.71 and 1.46 life-years, respectively, compared with universal radiation therapy. A strategy where patients with central tumors underwent stereotactic body radiotherapy and those with peripheral tumors underwent RFA resulted in a gain of 2.02 life-years compared with universal radiation therapy. Findings were robust with respect to changes in model parameters. CONCLUSION. Microsimulation modeling results suggest that RFA and stereotactic body radiotherapy could provide life expectancy gains to patients with stage IA or IB NSCLC who are ineligible for resection. C1 [Tramontano, Angela C.; Cipriano, Lauren E.; Kong, Chung Yin; Gazelle, G. Scott; McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Kong, Chung Yin; Shepard, Jo-Anne O.; Gazelle, G. Scott; McMahon, Pamela M.] Harvard Univ, Sch Med, Dept Div Radiol, Boston, MA USA. [Lanuti, Michael] Harvard Univ, Sch Publ Hlth, Dept Div Surg, Boston, MA 02115 USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP McMahon, PM (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St 10th Fl, Boston, MA 02114 USA. EM pamela@mgh-ita.org RI Cipriano, Lauren/C-3521-2017 OI Cipriano, Lauren/0000-0001-5568-4516 FU National Cancer Institute [R01 CA97337, K99/R00 CA126147]; American Cancer Society [2008A060554] FX This study was funded by the National Cancer Institute (grant R01 CA97337 and support to G. S. Gazelle, and grant K99/R00 CA126147 to P. M. McMahon) and the American Cancer Society (grant 2008A060554 to G. S. Gazelle). The National Electrical Manufacturers Association provided G. S. Gazelle and A. C. Tramontano with funding for an unrelated project. In March 2010, G. S. Gazelle became a consultant to GE Healthcare on projects not directly related to lung cancer screening. None of the other authors has any conflicts of interest. NR 40 TC 4 Z9 4 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2013 VL 200 IS 5 BP 1020 EP 1027 DI 10.2214/AJR.12.8968 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 133DD UT WOS:000318116700036 PM 23617484 ER PT J AU Kim, KW Ramaiya, NH Krajewski, KM Shinagare, AB Howard, SA Jagannathan, JP Ibrahim, N AF Kim, Kyung Won Ramaiya, Nikhil H. Krajewski, Katherine M. Shinagare, Atul B. Howard, Stephanie A. Jagannathan, Jyothi P. Ibrahim, Nageatte TI Ipilimumab-Associated Colitis: CT Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE colitis; CT; diverticulosis; ipilimumab; segmental colitis ID INFLAMMATORY-BOWEL-DISEASE; ADVERSE EVENTS; ANTI-CTLA-4 ANTIBODIES; METASTATIC MELANOMA; CANCER; DIVERTICULOSIS; MANAGEMENT; THERAPY; PATTERNS; UPDATE AB OBJECTIVE. The purpose of this article is to describe the CT findings of ipilimumab-associated colitis. MATERIALS AND METHODS. In this retrospective study, 16 patients diagnosed with ipilimumab-associated colitis and available CT scans obtained at the time of symptoms were found by a search through the electronic medical record database. Two radiologists reviewed the CT images in consensus for the presence of bowel wall thickening, bowel mucosal enhancement, bowel distention, pneumatosis, pericolic fat stranding, and mesenteric vessel engorgement. Medical records were reviewed to note clinical features, management, and outcome. RESULTS. The common CT findings of ipilimumab-associated colitis were mesenteric vessel engorgement (13/16 [81.3%]) followed by bowel wall thickening (12/16 [75%]) and fluid-filled colonic distention (4/16 [25%]). None of the patients had pneumatosis or halo or target signs. Two distinct CT patterns of ipilimumab-associated colitis were observed: first, the diffuse colitis pattern (n = 12), which is characterized by mesenteric vessel engorgement with mild diffuse bowel wall thickening or fluid-filled distended colon; and, second, the segmental colitis associated with diverticulosis (SCAD) pattern (n = 4), which is characterized by segmental moderate wall thickening and associated pericolic fat stranding in a segment of preexisting diverticulosis. Clinical features and management also differed according to the CT pattern. Patients with the diffuse colitis pattern presented with watery diarrhea and were treated with steroids, whereas the patients with the SCAD pattern presented with mixed watery and bloody diarrhea and cramping pain and were treated with steroids and antibiotics. CONCLUSION. Two different radiologic and clinical manifestations of ipilimumab-associated colitis were observed: the diffuse colitis pattern and the SCAD pattern. C1 [Kim, Kyung Won; Ramaiya, Nikhil H.; Krajewski, Katherine M.; Shinagare, Atul B.; Howard, Stephanie A.; Jagannathan, Jyothi P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Kim, Kyung Won] Univ Ulsan, Coll Med, Seoul Asan Med Ctr, Dept Radiol, Seoul, South Korea. [Kim, Kyung Won] Univ Ulsan, Coll Med, Seoul Asan Med Ctr, Res Inst Radiol, Seoul, South Korea. [Ibrahim, Nageatte] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. RP Kim, KW (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM medimash@gmail.com NR 24 TC 24 Z9 24 U1 1 U2 6 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 MAY PY 2013 VL 200 IS 5 BP W468 EP W474 DI 10.2214/AJR.12.9751 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 133DD UT WOS:000318116700008 PM 23718569 ER PT J AU Niell, B Specht, M Rafferty, E AF Niell, Bethany Specht, Michelle Rafferty, Elizabeth TI Lobular Neoplasia: What Does It Mean and How Should It Be Treated? Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID EXCISIONAL BIOPSY C1 [Niell, Bethany; Specht, Michelle; Rafferty, Elizabeth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. RP Niell, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2013 VL 200 IS 5 BP W539 EP W539 DI 10.2214/AJR.12.10289 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 133DD UT WOS:000318116700021 PM 23617528 ER PT J AU Walker, CM Chung, JH Abbott, GF Shepard, JO AF Walker, Christopher M. Chung, Jonathan H. Abbott, Gerald F. Shepard, JoAnne O. TI MRI in Lymph Node Staging of Lung Cancer Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID QUALITATIVE ASSESSMENT; N-STAGE; PET/CT; EFFICACY C1 [Walker, Christopher M.; Abbott, Gerald F.; Shepard, JoAnne O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Chung, Jonathan H.] Natl Jewish Hlth, Denver, CO USA. RP Walker, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2013 VL 200 IS 5 BP W541 EP W541 DI 10.2214/AJR.12.10142 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 133DD UT WOS:000318116700023 PM 23617530 ER PT J AU Okumi, M Scalea, JR Gillon, BC Tasaki, M Villani, V Cormack, T Hirakata, A Shimizu, A Sachs, DH Yamada, K AF Okumi, M. Scalea, J. R. Gillon, B. C. Tasaki, M. Villani, V. Cormack, T. Hirakata, A. Shimizu, A. Sachs, D. H. Yamada, K. TI The Induction of Tolerance of Renal Allografts by Adoptive Transfer in Miniature Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Adoptive transfer; kidney transplantation; MGH miniature swine; tolerance ID REGULATORY T-CELLS; TUBULAR EPITHELIAL-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; PERIPHERAL-BLOOD LYMPHOCYTES; TRANSPLANTATION TOLERANCE; CLASS-I; ANTIGEN PRESENTATION; KIDNEY ALLOGRAFTS; THYMUS; MODEL AB Our previous in vitro data have demonstrated that regulatory mechanisms are involved in tolerance of class I-mismatched renal allografts in miniature swine treated with 12 days of high dose Cyclsporin A. In this study, we attempted to induce tolerance of class I-mismatched kidneys by adoptive transfer of cells and/or kidneys from long-term tolerant animals. Fifteen SLAdd miniature swine received 1.5 Gy whole body irradiation and class I-mismatched (SLAgg) kidneys from naive pigs with or without cotransplanted kidneys and/or adoptively transferred cells from long-term tolerant (LTT) SLAdd recipients of SLAgg grafts. In addition, three SLAdd miniature swine received class I mismatched kidney with adoptively transferred cells from LTT SLAdd recipients. Naive kidneys transplanted without a LTT kidney were rejected within 9 days. All recipients of naive kidneys along with cells and kidney grafts from LTT animals showed markedly prolonged survival of the naive renal grafts (day 28, >150 and >150 days). These studies suggest that (1) tolerated kidneys have potent regulatory effects and (2) cells from LTT animals infused in conjunction with kidney grafts augment these regulatory effects. To our knowledge, these studies represent the first demonstration of successful adoptive transfer of tolerance in large animals. C1 [Okumi, M.; Scalea, J. R.; Gillon, B. C.; Tasaki, M.; Villani, V.; Cormack, T.; Hirakata, A.; Shimizu, A.; Sachs, D. H.; Yamada, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM kaz.yamada@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU NIH/NIAID [4R37AI031046-21, 1CO6RR20135-01] FX This work was supported by NIH/NIAID 4R37AI031046-21 and 1CO6RR20135-01. NR 36 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2013 VL 13 IS 5 BP 1193 EP 1202 DI 10.1111/ajt.12194 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 135GR UT WOS:000318277100011 PM 23464595 ER PT J AU Mengel, M Chan, S Climenhaga, J Kushner, YB Regele, H Colvin, RB Randhawa, P AF Mengel, M. Chan, S. Climenhaga, J. Kushner, Y. B. Regele, H. Colvin, R. B. Randhawa, P. TI Banff Initiative for Quality Assurance in Transplantation (BIFQUIT): Reproducibility of C4d Immunohistochemistry in Kidney Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Banff classification; C4d; immunohistochemistry; transplantation ID ANTIBODY-MEDIATED REJECTION; PERITUBULAR CAPILLARY; IMPROVE REPRODUCIBILITY; RENAL-ALLOGRAFTS; BIOPSIES; CLASSIFICATION; DEPOSITION; DIAGNOSIS; PATHOLOGY; ASSOCIATION AB Detection of C4d is crucial for diagnosing antibody-mediated-rejection. We conducted a multicenter trial to assess the reproducibility for C4d immunohistochemistry on paraffin tissue. Unstained slides from a tissue microarray (TMA) comprising 44 kidney allograft specimens representing a full analytical spectrum for C4d were distributed to 73 institutions. Participants stained TMA slides using local protocols and evaluated their slides following the Banff C4d schema. Local staining details and evaluation scores were collected online. Stained slides were returned for centralized panel re-evaluation. Kappa statistics were used to determine reproducibility. Poor interinstitutional reproducibility was observed (kappa 0.17), which was equally due to limitations in interobserver (kappa 0.44) and interlaboratory reproducibility (kappa 0.46). Depending on the cut-off, reproducibility could be improved by omitting C4d grading and only considering +/- calls. Heat-induced epitope recovery (pH 67, 2030 min, citrate buffer) with polyclonal antibody incubation (<1:80, >40 min) appeared as best practice. The BIFQUIT trial results indicated that C4d staining on paraffin sections varies considerably between laboratories. Refinement of the current Banff C4d scoring schema and harmonization of tissue processing and staining protocols is necessary to achieve acceptable reproducibility. C1 [Mengel, M.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Chan, S.; Climenhaga, J.] Univ Alberta, Dept Med, Alberta Transplant Appl Genom Ctr, Div Nephrol & Immunol, Edmonton, AB, Canada. [Kushner, Y. B.; Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kushner, Y. B.; Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Regele, H.] Med Univ Innsbruck, Inst Pathol, A-6020 Innsbruck, Austria. [Randhawa, P.] Univ Pittsburgh, Dept Pathol, Div Transplantat Pathol, Pittsburgh, PA USA. RP Mengel, M (reprint author), Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. EM mmengel@ualberta.ca FU Astellas Canada Inc. FX We thank Victoria Sheldon and Akshatha Raghuveer for an outstanding logistical support. This trial was supported by a research grant from Astellas Canada Inc. to M. M for facilitating Banff Working Group activities. NR 29 TC 17 Z9 19 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2013 VL 13 IS 5 BP 1235 EP 1245 DI 10.1111/ajt.12193 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 135GR UT WOS:000318277100015 PM 23464533 ER PT J AU Chen, GD Ko, DSC Wang, CX Qiu, J Han, M He, XS Chen, LZ AF Chen, G. -D. Ko, D. Shiu-Chung Wang, C. -X. Qiu, J. Han, M. He, X. -S. Chen, L. -Z. TI Kidney Transplantation From Donors After Cardiac Death: An Initial Report of 71 Cases From China SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Cardiac death donors; kidney transplantation; outcome; risk factors ID DONATION; RECIPIENTS AB Shortage of deceased donors is a severe problem in recent years in China especially in a culture in which brain death criteria is not widely accepted. Donation after cardiac death (DCD) has been reported to expand the donor pool despite higher rates of primary nonfunction (PNF) and delayed graft function (DGF) after transplantation. We collected 71 DCD kidney transplants performed at our hospital between February, 2007 and June, 2012 with aims to demonstrate the feasibility of DCD donation in China. All patients were followed up, and postoperative complications and graft loss were recorded. The PNF rate was 2.8%, and DGF rate was 28.2%. The 1- and 3-year graft survival was 95.7% and 92.4%. In conclusion, graft survival of DCD kidney transplantation in China is excellent despite of higher rates of PNF and DGF after transplantation. C1 [Chen, G. -D.; Wang, C. -X.; Qiu, J.; Han, M.; He, X. -S.; Chen, L. -Z.] Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Ko, D. Shiu-Chung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. [Ko, D. Shiu-Chung] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP He, XS (reprint author), Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510275, Guangdong, Peoples R China. EM gdtrc@163.com; clz@medmail.com.cn FU 5010 Clinical Research Project of Sun Yat-sen University [2007003]; Ministry of Health [2010159]; Division of Medical Service Management of Ministry of Health; Special Fund for Science Research by Ministry of Health [201002004] FX This study was supported by the 5010 Clinical Research Project of Sun Yat-sen University (2007003), the Key Clinical Project from the Ministry of Health (2010159), the Special Fund for Science Research by Ministry of Health (201002004) and Project by Division of Medical Service Management of Ministry of Health (2010). NR 10 TC 13 Z9 22 U1 1 U2 8 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 MAY PY 2013 VL 13 IS 5 BP 1323 EP 1326 DI 10.1111/ajt.12190 PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 135GR UT WOS:000318277100024 PM 23464380 ER PT J AU Graham, LA Maddox, TM Itani, KMF Hawn, MT AF Graham, Laura A. Maddox, Thomas M. Itani, Kamal M. F. Hawn, Mary T. TI Coronary Stents and Subsequent Surgery: Reported Provider Attitudes and Practice Patterns SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 35th Annual Meeting for the Association-of-VA-Surgeons CY APR 10-12, 2011 CL Irvine, CA SP Assoc VA Surg, VA Hlth Serv Res & Dev (HSR&D) ID DRUG-ELUTING STENTS; PERIOPERATIVE CARDIOVASCULAR EVALUATION; NONCARDIAC SURGERY; BARE-METAL; IMPLEMENTATION; GUIDELINES; INTERVENTION; THROMBOSIS; FRAMEWORK; OUTCOMES AB Management of antiplatelet therapy in patients with cardiac stents who need subsequent surgery is complex. Current guidelines recommend delaying elective surgery or, if surgery is emergent, proceeding without aspirin cessation. This study assessed provider knowledge, attitudes, and practices for patients with cardiac stents needing subsequent surgery. A national survey was administered to Veterans Administration surgeons, anesthesiologists, and cardiologists. Questions examined guideline awareness and agreement, perceptions of bleeding risk and stent thrombosis, practice patterns for antiplatelet therapy management, and experience with perioperative stent thrombosis. Chi-square tests and generalized estimating equations were used to examine differences in reported practices. Among 295 respondents, guideline awareness (92%) and agreement (93%) were high but higher among cardiologists and anesthesiologists than surgeons. Guideline agreement and personal experience with stent thrombosis were also associated with reported practice patterns. In adjusted models for early surgeries, cardiologists and anesthesiologists were more likely to report continuation of dual therapy as compared with surgeons regardless of stent type (drug-eluting P = 0.03; bare metal P < 0.01). Despite successful guideline adoption, significant variations in practice patterns by provider type were found. Understanding reasons behind the variation and outcomes of various antiplatelet management strategies are important steps in optimizing care of patients with coronary stents undergoing noncardiac surgery. C1 [Graham, Laura A.; Hawn, Mary T.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Maddox, Thomas M.] Univ Colorado Denver, VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Itani, Kamal M. F.] Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. RP Hawn, MT (reprint author), Univ Alabama Birmingham, Dept Surg, Sect Gastrointestinal Surg, 1922 7th Ave South,KB 428, Birmingham, AL 35294 USA. EM Mary.Hawn@ccc.uab.edu NR 16 TC 3 Z9 3 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD MAY PY 2013 VL 79 IS 5 BP 514 EP 523 PG 10 WC Surgery SC Surgery GA 130VA UT WOS:000317947000013 PM 23635588 ER PT J AU Nagashima, M Yasuhara, S Martyn, JAJ AF Nagashima, Michio Yasuhara, Shingo Martyn, J. A. Jeevendra TI Train-of-Four and Tetanic Fade Are Not Always a Prejunctional Phenomenon as Evaluated by Toxins Having Highly Specific Pre- and Postjunctional Actions SO ANESTHESIA AND ANALGESIA LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; NONDEPOLARIZING MUSCLE-RELAXANTS; NEUROMUSCULAR-JUNCTION; BOTULINUM-TOXIN; MUSCARINIC AUTORECEPTORS; TRANSMITTER RELEASE; MOTOR-NERVE; RAT; INHIBITION; EXPRESSION AB BACKGROUND: Nerve-stimulated fade in muscle is generally accepted as a prejunctional phenomenon mediated by block of prejunctional acetylcholine receptors (AChRs) at the nerve terminal, whereas decrease of twitch tension is considered a postjunctional effect due to block of muscle AChRs. Using ligands with specific pre- or postjunctional effects only, we tested the hypothesis that fade is not necessarily a prejunctional phenomenon. METHODS: Neuromuscular function in rats was evaluated after IM (2.5 U) or IV (12.0 U) injection of botulinum toxin (Botx), or IV (250 mu g/kg) alpha-bungarotoxin (alpha-BTX) alone. The acute neuromuscular effects of IV 2 mg/kg dihydro-beta-erythroidine (DH beta E), alone and in combination with alpha-BTX, were also tested. Botx decreases vesicular release of ACh, and alpha-BTX binds to postjunctional nicotinic AChRs only, whereas DE beta E binds specifically to prejunctional alpha 3 beta 2 AChRs only. In view of the lack of acute effects of Botx even at 2 hours after IV injection, its neuromuscular effects were also evaluated at 24 hours after IM injection (0.6 U) and compared with IM injection of alpha-BTX (25 mu g/kg) or saline also given 24 hours earlier. The sciatic nerve-tibialis muscle preparation, during train-of-four and tetanic stimulation, was used to test neuromuscular effects in vivo. RESULTS: IV and IM Botx had no observable neuromuscular effects at 2 hours. IV alpha-BTX caused twitch depression within a few minutes, and significant fade (P = 0.002) at 75% of baseline twitch. tension; these effects persisted until the end of the observation period of 2 hours. IV DH beta E alone caused no significant change in single twitch (P = 0.899) or train-of-four ratio (P = 0.394), but significantly enhanced the fade of IV alpha-BTX (P = 0.001 at 75% of baseline twitch tension). IM Botx or alpha-BTX, at 24 hours after their injection, resulted in a significant decrease of single twitch and tetanic tensions (P < 0.0001), but Botx did not cause fade, whereas alpha-BTX caused significant (P < 0.0001) fade at 24 hours. The tibialis muscle weights and protein expression of alpha 1 subunit of AChR (Western blots) did not differ between Botx, alpha-BTX and saline-injected groups at 24 hours but increased in denervated muscle (positive control). CONCLUSIONS: Botx-induced decreased ACh release in and of itself does not cause fade but does cause decrease of absolute tensions. Decrease of available (functional) postjunctional AChRs by alpha-BTX did induce fade. The prejunctional fade effects of DH beta E on alpha 3 beta 2 AChRs become manifest only when the margin of safety was decreased by concomitant administration of alpha-BTX. Thus, fade during repetitive stimulation is not always a prejunctional phenomenon and may also reflect the decreased margin of safety of neurotransmission, which can be due to a pure postjunctional AChRs block or to a combination of both pre- and postjunctional AChRs block. Block of prejunctional alpha 3 beta 2 AChRs alone is not necessary and sufficient to cause fade. (Anesth Analg 2013;116:994-1000) C1 Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. RP Martyn, JAJ (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Shriners Hosp Children Bos, 51 Blossom St,Room 206, Boston, MA 02114 USA. EM jmartyn@partners.org OI Nagashima, Michio/0000-0001-7416-5367 FU National Institutes of Health [RO1 GM 05882, GM P50-2500]; SHC Research Philanthropy, Tampa, FL FX This research was supported, in part, by National Institutes of Health grant number RO1 GM 05882 and GM P50-2500, and by SHC Research Philanthropy, Tampa, FL (to J.A.J.M.) NR 27 TC 3 Z9 4 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 IS 5 BP 994 EP 1000 DI 10.1213/ANE.0b013e31828841e3 PG 7 WC Anesthesiology SC Anesthesiology GA 134ET UT WOS:000318193700010 PM 23477960 ER PT J AU Coppadoro, A Berra, L Bittner, EA Ecker, JL Pian-Smith, MCM AF Coppadoro, Andrea Berra, Lorenzo Bittner, Edward A. Ecker, Jeffrey L. Pian-Smith, May C. M. TI Altered Arterial Compliance in Hypertensive Pregnant Women Is Associated With Preeclampsia SO ANESTHESIA AND ANALGESIA LA English DT Article ID PULSE-WAVE ANALYSIS; INTRAUTERINE GROWTH RESTRICTION; SERUM URIC-ACID; GESTATIONAL HYPERTENSION; NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; RISK; ELASTICITY; PRESSURE; HISTORY AB BACKGROUND: Vascular alterations are present in pregnant women affected by preeclampsia. In this study, we assessed arterial compliance in women affected by hypertensive disorders of pregnancy. We hypothesized that arterial compliance is reduced in women affected by preeclampsia. METHODS: Forty-three hypertensive pregnant women undergoing evaluation for preeclampsia were studied. Clinical data about each patient and pregnancy were collected. Large (Cl) and small (C2) artery compliance were assessed by radial tonometry, while the patients underwent laboratory tests to diagnose preeclampsia. At the time of delivery, gestational age and newborn data were recorded. RESULTS: Eighteen women were diagnosed with preeclampsia. C2 levels were lower among preeclamptic versus hypertensive aproteinuric women (mean +/- SD, 4.5 +/- 1.3 vs 5.9 +/- 2.3 mL/mm Hg . 100, P = 0.013, 95% confidence interval [Cl] of difference 0.32-2.55), whereas C1 levels did not differ. In the preeclampsia group, C2 levels correlated with urine total protein concentrations measured the same day (Spearman rho = -0.49, P = 0.047, upper 95% CI -0.01) and with gestational age at first occurrence of hypertension (Spearman rho = 0.59, P = 0.010, lower 95% Cl 0.17). Among singleton gestations, C2 also correlated with newborn birth weight measured at delivery (Spearman rho = 0.43, P = 0.009, lower 95% Cl 0.11). Women who were hypertensive but aproteinuric at the time of compliance assessment, but who subsequently developed preeclampsia (n = 6), had C2 levels similar to those with an early diagnosis of preeclampsia (mean difference 0.37 mL/mm Hg . 100, 95% Cl -2.42 to 1.67) and lower C2 levels than women diagnosed with gestational hypertension (P = 0.019, 95% Cl 0.33-4.42 mL/mm Hg . 100). CONCLUSIONS: The noninvasive assessment of arterial elasticity may contribute toward characterization of the nature of the pathophysiology in pregnancy-induced hypertensive disorders. The vascular alterations of the small arteries, as assessed by C2, may reflect the "extent of vascular alterations present with preeclampsia. (Anesth Analg 2013;116:1050-56) C1 [Coppadoro, Andrea; Berra, Lorenzo; Bittner, Edward A.; Pian-Smith, May C. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ecker, Jeffrey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Pian-Smith, MCM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mpiansmith@partners.org FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX Supported by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. NR 32 TC 0 Z9 0 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 IS 5 BP 1050 EP 1056 DI 10.1213/ANE.0b013e318282dc58 PG 7 WC Anesthesiology SC Anesthesiology GA 134ET UT WOS:000318193700017 PM 23337414 ER PT J AU Bittner, EA Martyn, JAJ Gronert, GA AF Bittner, Edward A. Martyn, J. A. Jeevendra Gronert, Gerald A. TI The Decision to Use Succinylcholine for Critically III Patients Should Not Be Based on Duration of Time in the Intensive Care Unit Alone SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 [Bittner, Edward A.; Martyn, J. A. Jeevendra] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gronert, Gerald A.] Univ Calif Davis, Depatment Anesthesiol, Davis, CA 95616 USA. RP Bittner, EA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM ebittner@partners.org NR 3 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 IS 5 BP 1182 EP 1182 DI 10.1213/ANE.0b013e31828c0046 PG 1 WC Anesthesiology SC Anesthesiology GA 134ET UT WOS:000318193700031 PM 23606469 ER PT J AU Thilen, SR Bryson, CL Reid, RJ Wijeysundera, DN Weaver, EM Treggiari, MM AF Thilen, Stephan R. Bryson, Christopher L. Reid, Robert J. Wijeysundera, Duminda N. Weaver, Edward M. Treggiari, Miriam M. TI Patterns of Preoperative Consultation and Surgical Specialty in an Integrated Healthcare System SO ANESTHESIOLOGY LA English DT Article ID MAJOR NONCARDIAC SURGERY; MEDICAL CONSULTATION; PERIOPERATIVE MEDICINE; MANAGED CARE; INTERNISTS; INDEX; WASTE; COST AB Background: Many patients scheduled for elective surgery are referred for a preoperative medical consultation. Only limited data are available on factors associated with preoperative consultations. The authors hypothesized that surgical specialty contributes to variation in referrals for preoperative consultations. Methods: This is a cohort study using data from Group Health Cooperative, an integrated healthcare system. The authors included 13,673 patients undergoing a variety of common procedures-primarily low-risk surgeries-representing six surgical specialties, in 2005-2006. The authors identified consultations by family physicians, general internists, pulmonologists, or cardiologists in the 42 days preceding surgery. Multivariable logistic regression was used to estimate the association between surgical specialty and consultation, adjusting for potential confounders including the revised cardiac risk index, age, gender, Deyo comorbidity index, number of prescription medications, and 11 medication classes. Results: The authors found that 3,063 (22%) of all patients had preoperative consultations, with significant variation by surgical specialty. Patients having ophthalmologic, orthopedic, or urologic surgery were more likely to have consultations compared with those having general surgery-adjusted odds ratios (95% CI) of 3.8 (3.3-4.2), 1.5 (1.3-1.7), and 2.3 (1.8-2.8), respectively. Preoperative consultations were more common in patients with lower revised cardiac risk scores. Conclusion: There is substantial practice variation among surgical specialties with regard to the use of preoperative consultations in this integrated healthcare system. Given the large number of consultations provided for patients with low cardiac risk and for patients presenting for low-risk surgeries, their indications, the financial burden, and cost-effectiveness of consultations deserve further study. C1 [Bryson, Christopher L.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Reid, Robert J.] Grp Hlth Res Inst, Seattle, WA USA. [Thilen, Stephan R.; Treggiari, Miriam M.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Thilen, SR (reprint author), 325 9th Ave,Box 359724, Seattle, WA 98104 USA. EM sthilen@uw.edu OI Wijeysundera, Duminda/0000-0002-5897-8605 FU National Institutes of Health, Bethesda, Maryland [T32GM086270]; U.S. Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Center of Excellence; VA Puget Sound Health Care Systems, Seattle, Washington; Canadian Institutes of Health Research (Ottawa, Ontario, Canada); Department of Anesthesia at the University of Toronto, Toronto, Ontario, Canada; Group Health Research Institute, Seattle, Washington FX Supported by grant T32GM086270, National Institutes of Health, Bethesda, Maryland (to Dr. Thilen). This material is based on work supported by the U.S. Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Center of Excellence; VA Puget Sound Health Care Systems, Seattle, Washington. Supported by a Clinician Scientist Award from the Canadian Institutes of Health Research (Ottawa, Ontario, Canada), and a Merit Award from the Department of Anesthesia at the University of Toronto, Toronto, Ontario, Canada (to Dr. Wijeysundera). The authors were also supported by Group Health Research Institute, Seattle, Washington, who waived part of the indirect costs. Without this support this project may not have been possible. Meetings at which work has been presented: Preliminary data were presented at the 5th annual meeting of the Society for Perioperative Assessment and Quality Improvement, March 3, 2011, Miami Beach, Florida, and at the annual meeting of the American Society of Anesthesiologists, October 16, 2011, Chicago, Illinois. NR 30 TC 9 Z9 10 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2013 VL 118 IS 5 BP 1028 EP 1037 DI 10.1097/ALN.0b013e31828ea68a PG 10 WC Anesthesiology SC Anesthesiology GA 131BA UT WOS:000317964300008 PM 23503373 ER PT J AU Sonpavde, G Pagliaro, LC Buonerba, C Dorff, TB Lee, RJ Di Lorenzo, G AF Sonpavde, G. Pagliaro, L. C. Buonerba, C. Dorff, T. B. Lee, R. J. Di Lorenzo, G. TI Penile cancer: current therapy and future directions SO ANNALS OF ONCOLOGY LA English DT Review DE biologic agents; chemotherapy; combined modality therapy; molecular targets; penile cancer; radiotherapy ID SQUAMOUS-CELL CARCINOMA; LYMPH-NODE INVOLVEMENT; HUMAN-PAPILLOMAVIRUS DNA; SOUTHWEST-ONCOLOGY-GROUP; PROGNOSTIC-FACTORS; PHASE-II; UNITED-STATES; INTERSTITIAL BRACHYTHERAPY; BILATERAL LYMPHADENECTOMY; COMBINATION CHEMOTHERAPY AB Background: Penile cancer (PC) is a rare cancer in western countries, but is more common in parts of the developing world. Due to its rarity and the consequent lack of randomized trials, current therapy is based on retrospective studies and small prospective trials. Design: Studies of PC therapy were searched in PubMed and abstracts at major conferences. Results: PC is generally an aggressive malignancy characterized by early locoregional lymph node (LN) spread and later metastases in distant sites. Given the strong predictive value of LN involvement for overall survival, evaluating regional LNs is critical. Advanced LN involvement is increasingly being treated with multimodality therapy incorporating chemotherapy and/or radiation. A single superior cisplatin-based regimen has not been defined. Further advances may occur with a better collaboration on an international scale and comprehensive understanding of tumor biology. To this end, the preventive role of circumcision and understanding of the oncogenic roles of Human Papilloma Virus-16, and smoking may yield advances. Preliminary data suggest a role for agents targeting epidermal growth factor receptor and angiogenesis. Conclusion: Advances in therapy for PC will require efficient trial designs, synergistic collaboration, incentives to industry and the efforts of patient advocacy groups and venture philanthropists. C1 [Sonpavde, G.] UAB Comprehens Canc Ctr, Dept Med, Sect Med Oncol, Birmingham, AL USA. [Pagliaro, L. C.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Buonerba, C.; Di Lorenzo, G.] Univ Naples Federico II, Genitourinary Canc Sect, Naples, Italy. [Buonerba, C.; Di Lorenzo, G.] Univ Naples Federico II, Rare Canc Ctr, Naples, Italy. [Dorff, T. B.] Univ So Calif, Dept Med, Sect Med Oncol, Los Angeles, CA USA. [Lee, R. J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol,Dept Med,Med Sch, Boston, MA 02114 USA. RP Di Lorenzo, G (reprint author), Univ Naples Federico II, Genitourinary Canc Sect, Naples, Italy. EM giuseppedilorenzoncol@hotmail.com FU Pfizer; BMS; Novartis; Celgene; Sanofi-Aventis FX GS: Research support and/or advisory board of Pfizer, BMS, Novartis, Celgene, and Sanofi-Aventis. LCP: Consultant for Janssen and Research support from Pfizer and Celgene. CB and RJL: these authors have declared no conflicts of interest. TBD: speaker for Pfizer and Bayer. GDL: research support from Pfizer and advisory board of Sanofi, Janssen, Cilag and Novartis. NR 156 TC 36 Z9 38 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2013 VL 24 IS 5 BP 1179 EP 1189 DI 10.1093/annonc/mds635 PG 12 WC Oncology SC Oncology GA 132YQ UT WOS:000318105000006 PM 23293117 ER PT J AU Oakman, C Francis, PA Crown, J Quinaux, E Buyse, M De Azambuja, E Vila, MM Andersson, M Nordenskjold, B Jakesz, R Thurlimann, B Gutierrez, J Harvey, V Punzalan, L Dell'Orto, P Larsimont, D Steinberg, I Gelber, RD Piccart-Gebhart, M Viale, G Di Leo, A AF Oakman, C. Francis, P. A. Crown, J. Quinaux, E. Buyse, M. De Azambuja, E. Margeli Vila, M. Andersson, M. Nordenskjold, B. Jakesz, R. Thuerlimann, B. Gutierrez, J. Harvey, V. Punzalan, L. Dell'Orto, P. Larsimont, D. Steinberg, I. Gelber, R. D. Piccart-Gebhart, M. Viale, G. Di Leo, A. TI Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the Breast International Group 02-98 phase III trial SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant; breast cancer; chemotherapy; docetaxel; doxorubicin; sequential ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; PLUS CYCLOPHOSPHAMIDE; FOLLOW-UP; HIGH-RISK; CANCER; EPIRUBICIN; PACLITAXEL; THERAPY; WOMEN AB Background: In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. Methods: Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) x 4 -> classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) x 4 -> CMF; (iii) sequential docetaxel: A (75 mg/m(2)) x3 -> docetaxel (T) (100 mg/m(2)) x3. CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) x 4 -> CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. Results: Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. Conclusion: With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control. C1 [Oakman, C.; Di Leo, A.] Hosp Prato, Ist Toscano Tumori, Sandro Pitigliani Med Oncol Unit, I-59100 Prato, Italy. [Francis, P. A.] Peter MacCallum Canc Ctr, Breast Canc Serv, Melbourne, Vic, Australia. [Francis, P. A.] Australian & New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Francis, P. A.] Int Breast Canc Study Grp, Bern, Switzerland. [Crown, J.] Irish Clin Oncol Res Grp, Dublin, Ireland. [Quinaux, E.; Buyse, M.] Int Inst Drug Dev, Louvain, Belgium. [De Azambuja, E.; Punzalan, L.; Piccart-Gebhart, M.] Univ Libre Brussels, Inst Jules Bordet, Breast European Adjuvant Studies Team, Brussels, Belgium. [Margeli Vila, M.] Hosp Badalona Germans Trias & Pujol, Med Oncol Unit, Badalona, Spain. [Andersson, M.] Danish Breast Canc Cooperat Grp, Copenhagen, Denmark. [Nordenskjold, B.] Univ Sjukhuset, Swedish Breast Canc Grp, Linkoping, Sweden. [Jakesz, R.] Vienna Med Sch, Austrian Breast & Colorectal Canc Study Grp, Vienna, Austria. [Thuerlimann, B.] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, B.] Swiss Grp Clin Canc Reserch SAKK, Bern, Switzerland. [Gutierrez, J.] Clin Las Condes, Grp Oncol Cooperat Chileno Invest, Santiago, Chile. [Harvey, V.] Auckland City Hosp, Reg Canc & Blood Ctr, Auckland, New Zealand. [Dell'Orto, P.; Viale, G.] Univ Milan, Sch Med, Milan, Italy. [Dell'Orto, P.; Viale, G.] European Inst Oncol, Dept Pathol, Milan, Italy. [Larsimont, D.] Univ Libre Brussels, Inst Jules Bordet, Dept Pathol, Brussels, Belgium. [Steinberg, I.] Sanofi Oncol, Cambridge, England. [Gelber, R. D.] IBCSG, Ctr Stat, Boston, MA USA. [Gelber, R. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Piccart-Gebhart, M.] Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium. RP Di Leo, A (reprint author), Hosp Prato, Ist Toscano Tumori, Dept Oncol, Sandro Pitigliani Med Oncol Unit, Piazza Osped 2, I-59100 Prato, Italy. EM adileo@usl4.toscana.it RI Francis, Prudence/J-4003-2012 FU sanofi-aventis; Associazione Italiana Ricerca Cancro (AIRC), Milan, Italy; National Health and Medical Research Council [100925, 351164]; Sanofi; Roche; Novartis FX This work was sponsored and funded by sanofi-aventis. Transtax analyses were funded by Associazione Italiana Ricerca Cancro (AIRC), Milan, Italy. Funding was also provided by the National Health and Medical Research Council [grant numbers 100925, 351164] to the Australian New Zealand Breast Cancer Trials Group.; Employment is disclosed by IS [Sanofi pharmaceuticals (AVP global medical leader)]. Stock ownership is disclosed by IS (Sanofi pharmaceuticals). Consultancy is disclosed by ADL (Sanofi), BT (Sanofi), JG (Roche, Bristol Myer Squibb) and MP-G (Sanofi, Amgen, Bayer, Bristol Myer Squibb, Roche, Glaxosmithkline, Boehringer Inghelneim, PharmaMar). Honoraria is disclosed by ADL (Sanofi), BT (Sanofi), JC (Sanofi, Roche Genentech), JG (Novartis, Roche, BMS), PAF (Sanofi), MP-G (Sanofi, Amgen, Bayer, Bristol Myer Squibb, Roche, Glaxosmithkline, Boehringer, PharmaMar) and VH (Roche, Sanofi). Research funding is disclosed by BT (Sanofi), JC (Sanofi, Roche Genentech), MP-G (Sanofi, Amgen, Bayer, Bristol Myer Squibb, Roche, Glaxosmithkline, Boehringer Inghelneim, PharmaMar) and VH (Roche). Other remuneration, including travel grants, is dislcosed by BT (Sanofi), JG (Roche, Novartis) and PAF (Sanofi). All the remaining authors have declared no conflicts of interest. NR 33 TC 10 Z9 10 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2013 VL 24 IS 5 BP 1203 EP 1211 DI 10.1093/annonc/mds627 PG 9 WC Oncology SC Oncology GA 132YQ UT WOS:000318105000008 PM 23293111 ER PT J AU Ovrutsky, AR Chan, ED Kartalija, M Bai, XY Jackson, M Gibbs, S Falkinham, JO Iseman, MD Reynolds, PR McDonnell, G Thomas, V AF Ovrutsky, Alida R. Chan, Edward D. Kartalija, Marinka Bai, Xiyuan Jackson, Mary Gibbs, Sara Falkinham, Joseph O., III Iseman, Michael D. Reynolds, Paul R. McDonnell, Gerald Thomas, Vincent TI Cooccurrence of Free-Living Amoebae and Nontuberculous Mycobacteria in Hospital Water Networks, and Preferential Growth of Mycobacterium avium in Acanthamoeba lenticulata SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID DRINKING-WATER; MOLECULAR-IDENTIFICATION; DISINFECTION TREATMENTS; DISTRIBUTION-SYSTEMS; RESISTING BACTERIA; INFECTIONS; KERATITIS; HEALTH; BIODIVERSITY; ENDOSYMBIONT AB The incidence of lung and other diseases due to nontuberculous mycobacteria (NTM) is increasing. NTM sources include potable water, especially in households where NTM populate pipes, taps, and showerheads. NTM share habitats with free-living amoebae (FLA) and can grow in FLA as parasites or as endosymbionts. FLA containing NTM may form cysts that protect mycobacteria from disinfectants and antibiotics. We first assessed the presence of FLA and NTM in water and biofilm samples collected from a hospital, confirming the high prevalence of NTM and FLA in potable water systems, particularly in biofilms. Acanthamoeba spp. (genotype T4) were mainly recovered (8/17), followed by Hartmannella vermiformis (7/17) as well as one isolate closely related to the genus Flamella and one isolate only distantly related to previously described species. Concerning mycobacteria, Mycobacterium gordonae was the most frequently found isolate (9/17), followed by Mycobacterium peregrinum (4/17), Mycobacterium chelonae (2/17), Mycobacterium mucogenicum (1/17), and Mycobacterium avium (1/17). The propensity of Mycobacterium avium hospital isolate H87 and M. avium collection strain 104 to survive and replicate within various FLA was also evaluated, demonstrating survival of both strains in all amoebal species tested but high replication rates only in Acanthamoeba lenticulata. As A. lenticulata was frequently recovered from environmental samples, including drinking water samples, these results could have important consequences for the ecology of M. avium in drinking water networks and the epidemiology of disease due to this species. C1 [Ovrutsky, Alida R.; Chan, Edward D.; Kartalija, Marinka; Bai, Xiyuan; Iseman, Michael D.; Reynolds, Paul R.] Natl Jewish Hlth, Denver, CO USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Jackson, Mary; Gibbs, Sara] Colorado State Univ, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Ovrutsky, Alida R.; Chan, Edward D.; Bai, Xiyuan; Iseman, Michael D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Kartalija, Marinka; Iseman, Michael D.] Univ Colorado, Div Infect Dis, Denver, CO 80202 USA. [Falkinham, Joseph O., III] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. [McDonnell, Gerald; Thomas, Vincent] STERIS Corp, Paris, France. RP Thomas, V (reprint author), STERIS Corp, Paris, France. EM chane@njhealth.org; vincethom2009@yahoo.fr RI Jackson, Mary/D-5345-2017; Thomas, Vincent/A-8941-2012 OI Thomas, Vincent/0000-0003-4034-9525 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases [AI089718] FX This work was supported in part by National Institutes of Health/National Institute of Allergy and Infectious Diseases grant AI089718. NR 46 TC 29 Z9 31 U1 2 U2 33 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAY PY 2013 VL 79 IS 10 BP 3185 EP 3192 DI 10.1128/AEM.03823-12 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 132AJ UT WOS:000318039800006 PM 23475613 ER PT J AU Gradl, G Gradl, G Wendt, M Mittlmeier, T Kundt, G Jupiter, JB AF Gradl, Georg Gradl, Gertraud Wendt, Martina Mittlmeier, Thomas Kundt, Guenther Jupiter, Jesse B. TI Non-bridging external fixation employing multiplanar K-wires versus volar locked plating for dorsally displaced fractures of the distal radius SO ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY LA English DT Article DE Distal radius fracture; External fixation; Non-bridging; Functional outcome; Volar plating ID INTRAARTICULAR FRACTURES; UNSTABLE FRACTURES; INTERNAL-FIXATION; OPEN REDUCTION; PART; COMPLICATIONS; WRIST; TRIAL AB The aim of this study was to compare non-bridging external fixation to palmar angular stable plating with respect to radiological outcome, wrist function, and quality of life. One hundred and two consecutive patients (mean age: 63 years) were enrolled in the study. Fifty-two patients were randomized for plate osteosynthesis (2.4 mm, Synthes), 50 patients received non-bridging external fixation (AO small fixator). Objective (range of motion, grip strength), patient rated outcomes (quality of life, pain), and radiological outcome were assessed 8 weeks, 6 months, and 1 year after surgery. Loss of radial length of more than 3 mm was not detected in any group. Volar tilt was better restored by external fixation (7.2A degrees) than by volar plating (0.1A degrees). Wrist function was good in both groups. The external fixator was tolerated very well, and the quality of life assessment revealed comparable results in both groups. Osteoporosis was found in 54 % of patients and had no influence on radiological and functional outcome. Non-bridging external fixation employing multiplanar K-wires is a suitable treatment option in intra- and extra-articular fractures of the distal radius even in osteoporotic bone. Prospective randomized trial, Level I. C1 [Gradl, Georg; Wendt, Martina; Mittlmeier, Thomas] Univ Rostock, Surg Clin, Dept Trauma & Reconstruct Surg, D-18055 Rostock, Germany. [Gradl, Gertraud; Jupiter, Jesse B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Gradl, Georg] Univ Aachen, Dept Trauma & Reconstruct Surg, D-52074 Aachen, Germany. [Kundt, Guenther] Univ Rostock, Dept Med Informat & Biometry, D-18057 Rostock, Germany. RP Gradl, G (reprint author), Univ Aachen, Dept Trauma & Reconstruct Surg, Pauwelstr 30, D-52074 Aachen, Germany. EM ggradl@ukaachen.de FU AO FX The study was supported by a grant from the AO. NR 35 TC 15 Z9 15 U1 1 U2 5 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 MAY PY 2013 VL 133 IS 5 BP 595 EP 602 DI 10.1007/s00402-013-1698-5 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 131DL UT WOS:000317972300002 PM 23420065 ER PT J AU Bowden, MG Behrman, AL Neptune, RR Gregory, CM Kautz, SA AF Bowden, Mark G. Behrman, Andrea L. Neptune, Richard R. Gregory, Chris M. Kautz, Steven A. TI Locomotor Rehabilitation of Individuals With Chronic Stroke: Difference Between Responders and Nonresponders SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Hemiparesis; Rehabilitation; Stroke; Walking ID RANDOMIZED CONTROLLED-TRIAL; BODY-WEIGHT SUPPORT; DYNAMIC GAIT INDEX; TREADMILL; WALKING; POSTSTROKE; RECOVERY; PERFORMANCE; SURVIVORS; SCALE AB Objectives: To identify the clinical measures associated with improved walking speed after locomotor rehabilitation in individuals poststroke and how those who respond with clinically meaningful changes in walking speed differ from those with smaller speed increases. Design: A single group pre-post intervention study. Participants were stratified on the basis of a walking speed change of greater than (responders) or less than (nonresponders) .16m/s. Paired sample t tests were run to assess changes in each group, and correlations were run between the change in each variable and change in walking speed. Setting: Outpatient interdisciplinary rehabilitation research center. Participants: Hemiparetic subjects (N=27) (17 left hemiparesis; 19 men; age: 58.74 +/- 12.97y; 22.70 +/- 16.38mo poststroke). Intervention: A 12-week locomotor intervention incorporating training on a treadmill with body weight support and manual trainers accompanied by training overground walking. Main Outcome Measures: Measures of motor control, balance, functional walking ability, and endurance were collected at pre- and postintervention assessments. Results: Eighteen responders and 9 nonresponders differed by age (responders=63.6y, nonresponders=49.0y, P=.001) and the lower extremity Fugl-Meyer Assessment score (responders=24.7, nonresponders=19.9, P=.003). Responders demonstrated an average improvement of .27m/s in walking speed as well as significant gains in all variables except daily step activity and paretic step ratio. Conversely, nonresponders demonstrated statistically significant improvements only in walking speed and endurance. However, the walking speed increase of .10m/s was not clinically meaningful. Change in walking speed was negatively correlated with changes in motor control in the nonresponder group, implying that walking speed phis may have been accomplished via compensatory mechanisms. Conclusions: This study is a step toward discerning the underlying factors contributing to improved walking performance. Archives of Physical Medicine and Rehabilitation 2013;94:856-62 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Bowden, Mark G.; Gregory, Chris M.; Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Bowden, Mark G.; Gregory, Chris M.; Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Bowden, Mark G.; Gregory, Chris M.; Kautz, Steven A.] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. [Behrman, Andrea L.] Univ Florida, Dept Phys Therapy, Gainesville, FL USA. [Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. RP Bowden, MG (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St,MSC 700, Charleston, SC 29425 USA. EM bowdenm@musc.edu OI Kautz, Steven/0000-0003-3151-8235 FU VA Merit Review [B3983-R]; VA Center of Excellence [F2182C]; VA Career Development Award [B7177]; National Institutes of Health - National Center for Medical and Rehabilitation Research (NICHD) [K12 HD055929]; National Institute for Neurological Disorders Stroke FX Supported by VA Merit Review (grant no. B3983-R); VA Center of Excellence (grant no. F2182C) (Brain Rehabilitation Research Center); VA Career Development Award (Phase I): B7177; and K12 HD055929 National Institutes of Health - National Center for Medical and Rehabilitation Research (NICHD) and National Institute for Neurological Disorders & Stroke. NR 46 TC 26 Z9 27 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2013 VL 94 IS 5 BP 856 EP 862 DI 10.1016/j.apmr.2012.11.032 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 134HX UT WOS:000318202100009 PM 23220082 ER PT J AU Ibrahim, SA Hanusa, BH Hannon, MJ Kresevic, D Long, J Kwoh, CK AF Ibrahim, Said A. Hanusa, Barbara H. Hannon, Michael J. Kresevic, Denise Long, Judith Kwoh, C. Kent TI Willingness and Access to Joint Replacement Among African American Patients With Knee Osteoarthritis: A Randomized, Controlled Intervention SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TOTAL HIP-ARTHROPLASTY; ETHNIC-DIFFERENCES; RACIAL DISPARITIES; PROBLEM DRINKERS; UNITED-STATES; ARTHRITIS; PREVALENCE; SURGERY; CARE; EXPECTATIONS AB Objective African American patients are significantly less likely to undergo knee replacement for the management of knee osteoarthritis (OA). Racial difference in preference (willingness) has emerged as a key factor. This study was undertaken to examine the efficacy of a patient-centered educational intervention on patient willingness and the likelihood of receiving a referral to an orthopedic clinic. Methods A total of 639 African American patients with moderate-to-severe knee OA from 3 Veterans Affairs primary care clinics were enrolled in a randomized, controlled trial with a 2 x 2 factorial design. Patients were shown a knee OA decision-aid video with or without brief counseling. The main outcome measures were change in patient willingness and receipt of a referral to an orthopedic clinic. Also assessed were whether patients discussed knee pain with their primary care provider or saw an orthopedic surgeon within 12 months of the intervention. Results At baseline, 67% of the participants were definitely/probably willing to consider knee replacement, with no difference among the groups. The intervention increased patient willingness (75%) in all groups at 1 month. For those who received the decision aid intervention alone, the gains were sustained for up to 3 months. By 12 months postintervention, patients who received any intervention were more likely to report engaging their provider in a discussion about knee pain (92% versus 85%), to receive a referral to an orthopedic surgeon (18% versus 13%), and for those with a referral, to attend an orthopedic consult (61% versus 50%). Conclusion An educational intervention significantly increased the willingness of African American patients to consider knee replacement. It also improved the likelihood of patientprovider discussion about knee pain and access to surgical evaluation. C1 [Ibrahim, Said A.; Long, Judith] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ibrahim, Said A.; Long, Judith] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hanusa, Barbara H.; Hannon, Michael J.; Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hannon, Michael J.; Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kresevic, Denise] Univ Hosp Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Kresevic, Denise] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Ibrahim, SA (reprint author), Univ Penn, Perelman Sch Med, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr Annex, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM said.ibrahim2@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR 05-234-2]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [1K24-AR-055259-01] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (grant IIR 05-234-2 to Dr. Ibrahim). Dr. Ibrahim's work also was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 1K24-AR-055259-01). NR 43 TC 11 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2013 VL 65 IS 5 BP 1253 EP 1261 DI 10.1002/art.37899 PG 9 WC Rheumatology SC Rheumatology GA 133WC UT WOS:000318170600015 PM 23613362 ER PT J AU Riddle, DL Singh, JA Harmsen, WS Schleck, CD Lewallen, DG AF Riddle, Daniel L. Singh, Jasvinder A. Harmsen, William S. Schleck, Cathy D. Lewallen, David G. TI Clinically Important Body Weight Gain Following Knee Arthroplasty: A Five-Year Comparative Cohort Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID ROCHESTER EPIDEMIOLOGY PROJECT; TOTAL HIP-ARTHROPLASTY; UNITED-STATES; RISK-FACTORS; OBESITY; ADULTS; POPULATION; OSTEOARTHRITIS; REPLACEMENT; HEALTH AB Objective The impact of knee arthroplasty on body weight has not been fully explored. Clinically important weight gain following knee arthroplasty would pose potentially important health risks. Methods We used one of the largest US-based knee arthroplasty registries and a population-based control sample from the same geographic region to determine whether knee arthroplasty increases the risk of clinically important weight gain of 5% of baseline body weight over a 5-year postoperative period. Results Of the persons in the knee arthroplasty sample, 30.0% gained 5% of baseline body weight 5 years following surgery as compared to 19.7% of the control sample. The multivariable-adjusted (age, sex, body mass index, education, comorbidity, and presurgical weight change) odds ratio (OR) was 1.6 (95% confidence interval [95% CI] 1.22.2) in persons with knee arthroplasty as compared to the control sample. Additional arthroplasty procedures during followup further increased the risk for weight gain (OR 2.1, 95% CI 1.43.1) relative to the control sample. Specifically, among patients with knee arthroplasty, younger patients and those who lost greater amounts of weight in the 5-year preoperative period were at greater risk for clinically important weight gain. Conclusion Patients who undergo knee arthroplasty are at an increased risk of clinically important weight gain following surgery. The findings potentially have broad implications to multiple members of the health care team. Future research should develop weight loss/maintenance interventions particularly for younger patients who have lost a substantial amount of weight prior to surgery, as they are most at risk for substantial postsurgical weight gain. C1 [Riddle, Daniel L.] Virginia Commonwealth Univ, Richmond, VA 23298 USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Harmsen, William S.; Schleck, Cathy D.; Lewallen, David G.] Mayo Clin, Rochester, MN USA. RP Riddle, DL (reprint author), Virginia Commonwealth Univ, Dept Phys Therapy, POB 980224, Richmond, VA 23298 USA. EM dlriddle@vcu.edu OI singh, jasvinder/0000-0003-3485-0006 FU Virginia Commonwealth University Presidential Research Initiative Program; URL; Savient; Novartis; Takeda; Allergan; Ardea; Osteotech; Zimmer FX Supported by a grant from the Virginia Commonwealth University Presidential Research Initiative Program.; Dr. Riddle has received honoraria (less than $10,000) for his role as Deputy Editor of Physical Therapy. Dr. Singh has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from URL, Savient, and Novartis, and (more than $10,000 each) from Takeda, Allergan, and Ardea, and has received investigator-initiated grants from Takeda and Savient. Dr. Lewallen has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Osteotech and Zimmer, and receives fees and royalties from Zimmer for hip and knee implants. NR 49 TC 10 Z9 10 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2013 VL 65 IS 5 BP 669 EP 677 DI 10.1002/acr.21880 PG 9 WC Rheumatology SC Rheumatology GA 133CJ UT WOS:000318114700002 PM 23203539 ER PT J AU Schmajuk, G Yazdany, J AF Schmajuk, Gabriela Yazdany, Jinoos TI Underestimation of the Reliability of Codes for Rheumatoid Arthritis Within Administrative Data: Comment on the Article by Ng et al SO ARTHRITIS CARE & RESEARCH LA English DT Letter ID VETERANS C1 [Schmajuk, Gabriela; Yazdany, Jinoos] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schmajuk, Gabriela] San Francisco VA Med Ctr, San Francisco, CA USA. RP Schmajuk, G (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2013 VL 65 IS 5 BP 835 EP 836 DI 10.1002/acr.21911 PG 2 WC Rheumatology SC Rheumatology GA 133CJ UT WOS:000318114700028 PM 23212977 ER PT J AU Ng, B Aslam, F Yu, HJ AF Ng, Bernard Aslam, Fawad Yu, Hong-Jen TI Underestimation of the Reliability of Codes for Rheumatoid Arthritis Within Administrative Data: Comment on the Article by Ng et al Reply SO ARTHRITIS CARE & RESEARCH LA English DT Letter ID DATABASES; DIAGNOSIS; ACCURACY C1 [Ng, Bernard; Yu, Hong-Jen] Michael E DeBakey VA Med Ctr Hlth Serv, Res & Dev Ctr Excellence, Houston, TX USA. [Ng, Bernard; Aslam, Fawad] Baylor Coll Med, Houston, TX 77030 USA. RP Ng, B (reprint author), Michael E DeBakey VA Med Ctr Hlth Serv, Res & Dev Ctr Excellence, Houston, TX USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2013 VL 65 IS 5 BP 836 EP 838 DI 10.1002/acr.21906 PG 3 WC Rheumatology SC Rheumatology GA 133CJ UT WOS:000318114700029 PM 23212929 ER PT J AU Michaelis, LC Saad, A Zhong, XB Le-Rademacher, J Freytes, CO Marks, DI Lazarus, HM Bird, JM Holmberg, L Kamble, RT Kumar, S Lill, M Meehan, KR Saber, W Schriber, J Tay, J Vogl, DT Wirk, B Savani, BN Gale, RP Vesole, DH Schiller, GJ Abidi, M Anderson, KC Nishihori, T Kalaycio, ME Vose, JM Moreb, JS Drobyski, W Munker, R Roy, V Ghobadi, A Holland, HK Nath, R To, LB Maiolino, A Kassim, AA Giralt, SA Landau, H Schouten, HC Maziarz, RT Mikhael, J Kindwall-Keller, T Stiff, PJ Gibson, J Lonial, S Krishnan, A Dispenzieri, A Hari, P AF Michaelis, Laura C. Saad, Ayman Zhong, Xiaobo Le-Rademacher, Jennifer Freytes, Cesar O. Marks, David I. Lazarus, Hillard M. Bird, Jennifer M. Holmberg, Leona Kamble, Rammurti T. Kumar, Shaji Lill, Michael Meehan, Kenneth R. Saber, Wael Schriber, Jeffrey Tay, Jason Vogl, Dan T. Wirk, Baldeep Savani, Bipin N. Gale, Robert P. Vesole, David H. Schiller, Gary J. Abidi, Muneer Anderson, Kenneth C. Nishihori, Taiga Kalaycio, Matt E. Vose, Julie M. Moreb, Jan S. Drobyski, William Munker, Reinhold Roy, Vivek Ghobadi, Armin Holland, H. Kent Nath, Rajneesh To, L. Bik Maiolino, Angelo Kassim, Adetola A. Giralt, Sergio A. Landau, Heather Schouten, Harry C. Maziarz, Richard T. Mikhael, Joseph Kindwall-Keller, Tamila Stiff, Patrick J. Gibson, John Lonial, Sagar Krishnan, Amrita Dispenzieri, Angela Hari, Parameswaran CA Ctr Int Blood Marrow Transplant TI Salvage Second Hematopoietic Cell Transplantation in Myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Second autologous transplantation; Multiple myeloma; Relapsed multiple myeloma ID DIAGNOSED MULTIPLE-MYELOMA; HIGH-DOSE THERAPY; ALLOGENEIC TRANSPLANTATION; AUTOLOGOUS TRANSPLANTATION; MARROW TRANSPLANTATION; RANDOMIZED TRIAL; SINGLE; BLOOD; CHEMOTHERAPY; SURVIVAL AB Autologous hematopoietic cell transplantation (AHCT) as initial therapy of patients with multiple myeloma (MM) improves survival. However, data to support this approach for relapsed/progressive disease after initial AHCT (AHCT1) are limited. Using Center for International Blood and Marrow Transplant Research data, we report the outcomes of 187 patients who underwent a second AHCT (AHCT2) for the treatment of relapsed/progressive MM. Planned tandem AHCT was excluded. Median age at AHCT2 was 59 years (range, 28 to 72), and median patient follow-up was 47 months (range, 3 to 97). Nonrelapse mortality after AHCT2 was 2% at 1 year and 4% at 3 years. Median interval from AHCT1 to relapse/progression was 18 months, and median interval between transplantations was 32 months. After AHCT2, the incidence of relapse/progression at 1 and 3 years was 51% and 82%, respectively. At 3 years after AHCT2, progression-free survival was 13%, and overall survival was 46%. In multivariate analyses, those relapsing >= 36 months after AHCT1 had superior progression-free (P = .045) and overall survival (P = .019). Patients who underwent AHCT2 after 2004 had superior survival (P = .026). AHCT2 is safe and feasible for disease progression after AHCT1. In this retrospective study, individuals relapsing >= 36 months from AHCT1 derived greater benefit from AHCT2 compared with those with a shorter disease-free interval. Storage of an adequate graft before AHCT1 will ensure that the option of a second autologous transplantation is retained for patients with relapsed/progressive MM. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Michaelis, Laura C.; Stiff, Patrick J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Saad, Ayman] Univ Alabama Birmingham, Birmingham, AL USA. [Zhong, Xiaobo; Le-Rademacher, Jennifer; Saber, Wael; Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Freytes, Cesar O.] UTHSC Vet Hlth Care Syst, San Antonio, TX USA. [Marks, David I.; Bird, Jennifer M.] Bristol Childrens Hosp, Bristol, Avon, England. [Lazarus, Hillard M.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Holmberg, Leona] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Kumar, Shaji; Dispenzieri, Angela] Mayo Clin, Rochester, MN USA. [Lill, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Meehan, Kenneth R.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Schriber, Jeffrey] City Hope Samaritan, Phoenix, AZ USA. [Tay, Jason] Univ Ottawa, Ottawa, ON, Canada. [Vogl, Dan T.] Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Wirk, Baldeep; Moreb, Jan S.] Shands Healthcare, Gainesville, FL USA. [Wirk, Baldeep; Moreb, Jan S.] Univ Florida, Gainesville, FL USA. [Savani, Bipin N.; Kassim, Adetola A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Gale, Robert P.] Univ London Imperial Coll Sci Technol & Med, Sect Hematol, London, England. [Vesole, David H.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Schiller, Gary J.] Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. [Abidi, Muneer] Wayne State Univ, Kamanos Canc Inst, Detroit, MI USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nishihori, Taiga] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Kalaycio, Matt E.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Vose, Julie M.] Nebraska Med Ctr, Omaha, NE USA. [Drobyski, William] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA. [Munker, Reinhold] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. [Roy, Vivek] Mayo Clin, Jacksonville, FL 32224 USA. [Ghobadi, Armin] Washington Univ, St Louis Childrens Hosp, St Louis, MO 63110 USA. [Holland, H. Kent] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Nath, Rajneesh] UMass Mem Med Ctr, Worcester, MA USA. [To, L. Bik] Royal Adelaide Hosp, Adelaide, SA 5000, Australia. [Maiolino, Angelo] Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil. [Giralt, Sergio A.; Landau, Heather] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Schouten, Harry C.] Acad Ziekenhuis Maastricht, Maastricht, Netherlands. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Mikhael, Joseph] Mayo Clin Arizona, Scottsdale, AZ USA. [Mikhael, Joseph] Phoenix Childrens Hosp, Scottsdale, AZ USA. [Kindwall-Keller, Tamila] Univ Virginia, Charlottesville, VA USA. [Gibson, John] Royal Prince Alfred Hosp, Inst Haematol, Camperdown, NSW 2050, Australia. [Lonial, Sagar] Emory Univ Hosp, Atlanta, GA 30322 USA. [Krishnan, Amrita] City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Hari, P (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Vogl, Dan/0000-0002-2935-2566; Hari, Parameswaran/0000-0002-8800-297X; Saad, Ayman /0000-0003-0003-0130; Dispenzieri, Angela/0000-0001-8780-9512 FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two grants, N00014-06-1-0704 and N00014-08-1-0058, from the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. NR 31 TC 34 Z9 34 U1 0 U2 8 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 MAY PY 2013 VL 19 IS 5 BP 760 EP 766 DI 10.1016/j.bbmt.2013.01.004 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133IQ UT WOS:000318132500013 PM 23298856 ER PT J AU Pidala, J Chai, XY Kurland, BF Inamoto, Y Flowers, MED Palmer, J Khera, N Jagasia, M Cutler, C Arora, M Vogelsang, G Lee, SJ AF Pidala, Joseph Chai, Xiaoyu Kurland, Brenda F. Inamoto, Yoshihiro Flowers, Mary E. D. Palmer, Jeanne Khera, Nandita Jagasia, Madan Cutler, Corey Arora, Mukta Vogelsang, Georgia Lee, Stephanie J. TI Analysis of Gastrointestinal and Hepatic Chronic Grant-versus-Host Disease Manifestations on Major Outcomes: A Chronic Grant-versus-Host Disease Consortium Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic GVHD; Gastrointestinal; Hepatic ID QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; NIH CONSENSUS CRITERIA; HEMATOPOIETIC-CELL TRANSPLANTATION; WORKING GROUP-REPORT; DEVELOPMENT PROJECT; CLINICAL-TRIALS; CHRONIC GVHD; SCALE; VALIDATION AB Although data support adverse prognosis of overlap subtype of chronic grant-versus-host disease (GVHD), the importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Using data from the Chronic GVHD Consortium observational cohort study (N = 567, total of 2115 visits), we examined whether the site of GI (esophageal, upper GI, or lower GI) and type of hepatic (bilirubin, alkaline phosphatase, alanine aminotransferase) involvement are associated with overall survival (OS) and nonrelapse mortality (NRM), symptoms, quality of life (QOL) and functional status measures. In multivariate analysis utilizing data from enrollment visits only, lower GI involvement (HR, 1.67; P = .05) and elevated bilirubin (HR, 2.46; P = .001) were associated with OS; both were also associated with NRM. In multivariable analysis using all visits (time-dependent covariates), GI score greater than zero (HR, 1.69; P = .02) and elevated bilirubin (HR, 3.73; P < .001) were associated with OS; results were similar for NRM. Any esophageal involvement and GI score greater than zero were associated with both symptoms and QOL, whereas elevated bilirubin was associated with QOL. We found no consistent evidence that upper GI involvement, alkaline phosphatase, alanine aminotransferase, or NIH liver score add prognostic value for survival, overall symptom burden, or QOL. These data support important differences in patient-reported outcomes according to GI and hepatic involvement among chronic GVHD-affected patients and identify those With elevated bilirubin or higher GI score at any time, or lower GI involvement at cohort enrollment, as patients at greater risk for mortality under current treatment approaches. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Pidala, Joseph] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Chai, Xiaoyu; Kurland, Brenda F.; Inamoto, Yoshihiro; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Khera, Nandita] Mayo Clin Arizona, Phoenix, AZ USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Vogelsang, Georgia] Johns Hopkins Univ, Baltimore, MD USA. RP Pidala, J (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM joseph.pidala@moffitt.org OI Kurland, Brenda/0000-0002-5669-0595 FU NIAID [U54 AI 083028]; [CA 118953] FX Supported by grant CA 118953 (PI: Stephanie J. Lee) and NIAID U54 AI 083028 (PI: Stephanie J. Lee). NR 33 TC 14 Z9 14 U1 0 U2 0 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 MAY PY 2013 VL 19 IS 5 BP 784 EP 791 DI 10.1016/j.bbmt.2013.02.001 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133IQ UT WOS:000318132500016 PM 23395601 ER PT J AU Nikiforow, S Kim, HT Bindra, B McDonough, S Glotzbecker, B Armand, P Koreth, J Ho, VT Alyea, EP Blazar, BR Ritz, J Soiffer, RJ Antin, JH Cutler, CS AF Nikiforow, Sarah Kim, Haesook T. Bindra, Bhavjot McDonough, Sean Glotzbecker, Brett Armand, Philippe Koreth, John Ho, Vincent T. Alyea, Edwin P., III Blazar, Bruce R. Ritz, Jerome Soiffer, Robert J. Antin, Joseph H. Cutler, Corey S. TI Phase I Study of Alemtuzumab for Therapy of Steroid-Refractory Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Alemtuzumab; Chronic graft-versus-host disease; Steroid refractory; Treatment ID CONSENSUS DEVELOPMENT PROJECT; STEM-CELL TRANSPLANTATION; WORKING GROUP-REPORT; CLINICAL-TRIALS; INDUCED RESOLUTION; CRITERIA; CD52; RECONSTITUTION; CAMPATH-1H; RESISTANT AB Steroid-refractory chronic graft-versus-host disease (cGVHD) carries a poor prognosis with no agreed upon algorithm for treatment. Because both B and T cells contribute to the pathophysiology of cGVHD, we conducted a phase I study in subjects with steroid-refractory cGVHD using the anti-CD52 antibody alemtuzumab to transiently deplete most mononuclear subsets. Three regimens were investigated in a 3+3 dose-escalation design: 3 mg x 6 (dose level 1), 3 mg x I, then 10 mg x 5 (dose level 2) and 3 mg x 1, 10 mg x 1, then 30 mg x 4 (dose level 3) administered over 4 weeks. The maximum tolerated dose of alemtuzumab was dose level 2. Thirteen patients were assessable for toxicities, which were primarily infectious and hematologic. Rates of infectious complications in the first 12 weeks were 0% at dose level 1 (n = 3), 50% at dose level 2 (1 death, n = 6), and 75% at dose level 3 (2 deaths, n = 4). Of 10 patients assessable for response, 7 (70%) responded at 12 weeks, with a 30% complete response rate. Four subjects reduced steroid dose or discontinued an immunosuppressant at 12 weeks. The median decrease in steroid dose at 1 year was 61.6%. Infectious complications occurred predominantly in the first 3 months after therapy, but full B and T cell recovery took well over 12 months. Immunophenotypic profiling revealed early recovery by natural killer cells and relative sparing of CD4+ and CD8+ central memory T cell subsets. Our study indicates that therapy with alemtuzumab for steroid-refractory cGVHD is tolerable with close attention to dosing and may be active in subjects who have failed multiple therapies. The pattern of lymphocyte recovery after alemtuzumab will inform the biology and future therapy of cGVHD. The use of alemtuzumab in the context of therapy for cGVHD deserves study in larger phase II trials. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Nikiforow, Sarah; Bindra, Bhavjot; McDonough, Sean; Glotzbecker, Brett; Armand, Philippe; Koreth, John; Ho, Vincent T.; Alyea, Edwin P., III; Ritz, Jerome; Soiffer, Robert J.; Antin, Joseph H.; Cutler, Corey S.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN USA. RP Nikiforow, S (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Smith 353,450 Brookline Ave, Boston, MA 02215 USA. EM sarah_nikiforow@dfci.harvard.edu FU Genzyme, Inc.; Gateway for Cancer Research [P-06-005]; National Institutes of Health [P-01 CA142106]; Stem Cell Cyclists of the Pan Mass Challenge FX Supported in part by Genzyme, Inc., the Gateway for Cancer Research (grant no. P-06-005), and the National Institutes of Health (grant no. P-01 CA142106). C.C. is supported by the Stem Cell Cyclists of the Pan Mass Challenge. S.N. is supported by the Friends of Dana-Farber. NR 32 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2013 VL 19 IS 5 BP 804 EP 811 DI 10.1016/j.bbmt.2013.02.009 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133IQ UT WOS:000318132500019 PM 23416855 ER PT J AU Zhan, HC Cardozo, C Raza, A AF Zhan, Huichun Cardozo, Christopher Raza, Azra TI MicroRNAs in myeloproliferative neoplasms SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE microRNA; myeloproliferative neoplasm; polycythaemia vera; essential thrombocythaemia; myelofibrosis ID HEMATOPOIETIC STEM-CELLS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; V617F MUTATION; C-MYB; MEGAKARYOCYTIC DIFFERENTIATION; ERYTHROID-DIFFERENTIATION; MICROPROCESSOR COMPLEX; NORMAL ERYTHROPOIESIS AB The chronic myeloproliferative neoplasms (MPN), including polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), are clonal stem cell disorders characterized by dysregulated haematopoietic stem cell expansion and production of red cells, white cells and platelets alone or in combination. An acquired mutation JAK2V617F can be found in all three disorders and shows many of the phenotypic abnormalities of the diseases in murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 1824 nucleotide single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. There is growing evidence that miRNAs regulate haematopoiesis in both haematopoietic stem cells and committed progenitor cells. Here, we review the field of miRNA biology and its regulatory roles in normal haematopoiesis with an emphasis on miRNA deregulations in MPNs. Continued research into how miRNAs impact JAK2V617F clonal expansion, differential haematopoiesis among different MPNs, disease progression and leukaemia transformation will lead to a better understanding of the development of these disorders, their clinical manifestations, and their treatment. C1 [Zhan, Huichun; Cardozo, Christopher] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Zhan, Huichun; Raza, Azra] Columbia Univ, Med Ctr, New York, NY USA. [Cardozo, Christopher] Mt Sinai Sch Med, New York, NY USA. RP Zhan, HC (reprint author), James J Peters VA Med Ctr, 3F-12,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Huichun.Zhan@va.gov FU Veterans Affairs (VA) Career Development Award [10959632]; VA Rehabilitation Research and Development Service Center [B9212-C] FX Huichun Zhan is currently supported by Veterans Affairs (VA) Career Development Award Grant 10959632 and VA Rehabilitation Research and Development Service Center Grant B9212-C. We are grateful to Dr Jerry L. Spivak from Johns Hopkins University for his valuable advice and critical review during the preparation of the manuscript. We thank Dr Haoyi Zheng from New York University Medical Center for his indispensable help in editing the manuscript. We thank Dr Naomi Galili from Columbia University Medical Center for reviewing the manuscript. NR 136 TC 17 Z9 18 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2013 VL 161 IS 4 BP 471 EP 483 DI 10.1111/bjh.12276 PG 13 WC Hematology SC Hematology GA 133WT UT WOS:000318172300004 PM 23432162 ER PT J AU Zhang, XH Wu, KN Cho, EY Ma, J Chan, AT Gao, X Willett, WC Fuchs, CS Giovannucci, EL AF Zhang, Xuehong Wu, Kana Cho, Eunyoung Ma, Jing Chan, Andrew T. Gao, Xiang Willett, Walter C. Fuchs, Charles S. Giovannucci, Edward L. TI Prospective cohort studies of bowel movement frequency and laxative use and colorectal cancer incidence in US women and men SO CANCER CAUSES & CONTROL LA English DT Article DE Bowel movement frequency; Laxative use; Colorectal cancer; Incidence; Prospective study; Latency ID UNITED-STATES; COLON-CANCER; RISK-FACTORS; CONSTIPATION; HEALTH; REPRODUCIBILITY; QUESTIONNAIRE; VALIDITY; POLYPS AB The associations between bowel movement frequency, laxative use, and colorectal cancer incidence remain uncertain. No published studies have accounted for potential latency between these factors and colorectal cancer onset. We prospectively examined these associations among 88,173 women in the Nurses' Health Study (NHS, 1982-2010) and 23,722 men in the Health Professionals Follow-up Study (HPFS, 2000-2010). Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs, 95 % CIs). We conducted time lagged analyses to evaluate the potential latency in the NHS. We documented 2,012 incident colorectal cancer cases. The HRs (95 % CIs) for infrequent bowel movement relative to daily were 0.86 (95 % CI 0.71-1.04) in women and 0.81 (95 % CI 0.48-1.37) in men. The HRs for weekly to daily relative to never laxative use were 0.98 (95 % CI 0.81-1.20) in women and 1.41 (95 % CI 0.96-2.06) in men. In women, the HRs for every 3 days or less bowel movement relative to daily were 0.87 (95 % CI 0.59-1.27) for colorectal cancers that developed within 10 years of assessment, 1.03 (95 % CI 0.85-1.26) for 11-18 years after assessment, and 0.73 (95 % CI 0.54-1.01) for 19-28 years after assessment. The corresponding HRs for weekly to daily relative to never laxative use were 0.93 (95 % CI 0.63-1.37), 1.03 (95 % CI 0.74-1.44), and 0.98 (95 % CI 0.71-1.35), respectively. Bowel movement frequency and laxative use appear not to be associated with colorectal cancer risk in this study. C1 [Zhang, Xuehong; Cho, Eunyoung; Ma, Jing; Chan, Andrew T.; Gao, Xiang; Willett, Walter C.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Zhang, Xuehong; Cho, Eunyoung; Ma, Jing; Chan, Andrew T.; Gao, Xiang; Willett, Walter C.; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wu, Kana; Cho, Eunyoung; Gao, Xiang; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ma, Jing; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zhang, XH (reprint author), Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 401 Pk Dr,Suite 301 WEST, Boston, MA 02115 USA. EM poxue@channing.harvard.edu FU NIH [CA87969, CA55075, CA137178] FX We would like to thank the participants and staff of the NHS and HPFS 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. The NIH grants CA87969, CA55075, and CA137178. Dr. Chan is a Damon Runyon Clinical Investigator. NR 25 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2013 VL 24 IS 5 BP 1015 EP 1024 DI 10.1007/s10552-013-0176-2 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 131ER UT WOS:000317975800017 PM 23456271 ER PT J AU Elkin, EB Nobles, JP Pinheiro, LC Atoria, CL Schrag, D AF Elkin, Elena B. Nobles, J. Paige Pinheiro, Laura C. Atoria, Coral L. Schrag, Deborah TI Changes in access to screening mammography, 2008-2011 SO CANCER CAUSES & CONTROL LA English DT Article DE Breast cancer; Screening; Mammography; Access to care AB Screening mammography is a cornerstone of preventive health care for adult women in the United States. As rates of screening mammography have declined and plateaued in the past decade, access to services remains a concern. In 2011, we repeated a survey of mammography facilities initially surveyed in 2008 in six states. The availability of digital mammography increased and appointment wait times generally improved between the two survey periods, but more facilities required payment upfront. Provisions of the federal healthcare reform law that eliminate cost sharing for selected preventive health services may improve access to screening mammography and prevent further declines in the rate of breast cancer screening. C1 [Elkin, Elena B.; Nobles, J. Paige; Pinheiro, Laura C.; Atoria, Coral L.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, New York, NY 10021 USA. [Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Elkin, EB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, New York, NY 10021 USA. EM elkine@mskcc.org FU NCI NIH HHS [K07 CA118189, P30 CA008748] NR 10 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2013 VL 24 IS 5 BP 1057 EP 1059 DI 10.1007/s10552-013-0180-6 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 131ER UT WOS:000317975800022 PM 23468282 ER PT J AU Chan, JA Mayer, RJ Jackson, N Malinowski, P Regan, E Kulke, MH AF Chan, Jennifer A. Mayer, Robert J. Jackson, Nadine Malinowski, Paige Regan, Eileen Kulke, Matthew H. TI Phase I study of sorafenib in combination with everolimus (RAD001) in patients with advanced neuroendocrine tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Neuroendocrine; Phase I; Sorafenib; Everolimus ID ENDOCRINE PANCREATIC TUMORS; RENAL-CELL CARCINOMA; EXPRESSION; METASTASES; SUNITINIB AB Sorafenib and everolimus are both active against neuroendocrine tumors (NET). Because of potential synergy between VEGF pathway and mTOR inhibitors, we performed a phase I study to evaluate the safety and feasibility of combining sorafenib and everolimus in patients with advanced NET. Patients were treated with everolimus 10 mg daily in combination with sorafenib (dose level 1: 200 mg twice daily; dose level 2: 200 mg per morning, 400 mg per evening) using standard phase I dose escalation design. Dose-limiting toxicity (DLT) was defined within the first cycle (28 days) of therapy. Treatment was continued until tumor progression, unacceptable toxicity, or withdrawal of consent. Twelve additional patients were treated at the maximum tolerated dose (MTD) level to further characterize safety and a preliminary assessment of activity. One patient in Cohort 1 experienced DLT (grade 3 skin rash); the cohort was expanded to 6 patients with no further DLTs. All 3 patients in Cohort 2 experienced DLT, consisting of thrombocytopenia, hand-foot skin reaction, and rash/allergic reaction. Sorafenib 200 mg twice daily in combination with everolimus 10 mg daily was established as the MTD. Independently reviewed best objective responses revealed that 62 % of patients had some degree of tumor shrinkage. By RECIST, we observed partial response in 1 patient, stable disease in 13 patients, and progressive disease in 3 patients. Sorafenib 200 mg twice daily with everolimus 10 mg daily represents the MTD of this combination in patients with advanced NET. While the combination is active, toxicity concerns may preclude more widespread use. C1 [Chan, Jennifer A.; Mayer, Robert J.; Jackson, Nadine; Malinowski, Paige; Regan, Eileen; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Chan, Jennifer A.; Mayer, Robert J.; Jackson, Nadine; Kulke, Matthew H.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM JANG@PARTNERS.ORG FU Saul and Gitta Kurlat fund for neuroendocrine tumor research; Novartis; Bayer; Onyx Pharmaceuticals; Schering-Plough/Merck FX The authors gratefully acknowledge support from the Saul and Gitta Kurlat fund for neuroendocrine tumor research. This work was supported by Novartis, Bayer, and Onyx Pharmaceuticals.; J. Chan: research funding from Novartis, Schering-Plough/Merck, Bayer, and Onyx Pharmaceuticals. NR 16 TC 14 Z9 14 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2013 VL 71 IS 5 BP 1241 EP 1246 DI 10.1007/s00280-013-2118-9 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 135KS UT WOS:000318287600014 PM 23475104 ER PT J AU O'Connor, R Ooi, MG Meiller, J Jakubikova, J Klippel, S Delmore, J Richardson, P Anderson, K Clynes, M Mitsiades, CS O'Gorman, P AF O'Connor, Robert Ooi, Melissa G. Meiller, Justine Jakubikova, Jana Klippel, Steffen Delmore, Jake Richardson, Paul Anderson, Kenneth Clynes, Martin Mitsiades, Constantine S. O'Gorman, Peter TI The interaction of bortezomib with multidrug transporters: implications for therapeutic applications in advanced multiple myeloma and other neoplasias SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE P-glycoprotein; MDR protein; Bortezomib; Elacridar; Co-culture ID NF-KAPPA-B; PROTEASOME INHIBITOR BORTEZOMIB; P-GLYCOPROTEIN EXPRESSION; NECROSIS-FACTOR-ALPHA; DRUG-RESISTANCE; IN-VITRO; TUMOR-CELLS; PHASE-III; LUNG-CARCINOMA; ONCOLOGY-GROUP AB Bortezomib is an important agent in multiple myeloma treatment, but resistance in cell lines and patients has been described. The main mechanisms of resistance described in cancer fall into one of two categories, pharmacokinetic resistance (PK), e.g. over expression of drug efflux pumps and pharmacodynamic resistance, e.g. apoptosis resistance or altered survival pathways, where the agent reaches an appropriate concentration, but this fails to propagate an appropriate cell death response. Of the known pump mechanisms, P-glycoprotein (P-gp) is the best studied and considered to be the most important in contributing to general PK drug resistance. Resistance to bortezomib is multifactorial and there are conflicting indications that cellular overexpression of P-gp may contribute to resistance agent. Hence, better characterization of the interactions of this drug with classical resistance mechanisms should identify improved treatment applications. Cell lines with different P-gp expression levels were used to determine the relationship between bortezomib and P-gp. Coculture system with stromal cells was used to determine the effect of the local microenvironment on the bortezomib-elacridar combination. To further assess P-gp function, intracellular accumulation of P-gp probe rhodamine-123 was utilised. In the present study, we show that bortezomib is a substrate for P-gp, but not for the other drug efflux transporters. Bortezomib activity is affected by P-gp expression and conversely, the expression of P-gp affect bortezomib's ability to act as a P-gp substrate. The local microenvironment did not alter the cellular response to bortezomib. We also demonstrate that bortezomib directly affects the expression and function of P-gp. Our findings strongly support a role for P-gp in bortezomib resistance and, therefore, suggest that combination of a P-gp inhibitor and bortezomib in P-gp positive myeloma would be a reasonable treatment combination to extend efficacy of this important drug. C1 [O'Connor, Robert] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland. [O'Connor, Robert; Ooi, Melissa G.; Meiller, Justine; Clynes, Martin; O'Gorman, Peter] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland. [Ooi, Melissa G.; Jakubikova, Jana; Klippel, Steffen; Delmore, Jake; Richardson, Paul; Anderson, Kenneth; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [O'Gorman, Peter] Mater Misericordiae Univ Hosp, Dept Haematol, Dublin 7, Ireland. RP Ooi, MG (reprint author), Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland. EM mgooi20@gmail.com OI o'connor, robert/0000-0003-4426-2507 FU Amgen Inc.; AVEO Pharma; Genzyme Corporation; Johnson & Johnson Pharmaceutical Research & Development, LLC. FX Dr. Kenneth Anderson disclosed the following relevant financial relationships: Served as a consultant for Celgene Corporation, Millennium Pharmaceuticals, Inc., Onyx Pharmaceuticals, Inc., Sanofi and Gilead. Stock Ownership in Oncopep and Acetylon Pharmaceuticals; Dr. Paul Richardson disclosed the following relevant financial relationships: Served as a consultant for Millennium Pharmaceuticals, Inc., and Johnson & Johnson Pharmaceutical Research & Development, LLC; Dr. Constantine Mitsiades disclosed the following relevant financial relationships: Received funding for clinical research from Amgen Inc., AVEO Pharma, Genzyme Corporation, Johnson & Johnson Pharmaceutical Research & Development, LLC. Served as a consultant or received honoraria from Bristol-Myers Squibb company, Millennium Pharmaceuticals, Inc., Celgene Corporation, Centocor Research & Development, Inc, Merck & Co., Inc., Novartis Pharmaceuticals Corporation; Dr. Steffen Klippel disclosed the following relevant financial relationships: Stock Ownership in Novartis Pharmaceuticals. The other authors have no disclosures. NR 51 TC 19 Z9 21 U1 2 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2013 VL 71 IS 5 BP 1357 EP 1368 DI 10.1007/s00280-013-2136-7 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 135KS UT WOS:000318287600026 PM 23589314 ER PT J AU Weinberg, I Giri, J Calfon, MA Hawkins, BM Weinberg, MD Margey, R Hannon, K Schainfeld, RM Jaff, MR AF Weinberg, Ido Giri, Jay Calfon, Marcella A. Hawkins, Beau M. Weinberg, Mitchell D. Margey, Ronan Hannon, Kathleen Schainfeld, Robert M. Jaff, Michael R. TI Anatomic correlates of supra-normal ankle brachial indices SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE ankle brachial index; peripheral artery disease; angiography; incompressible vessels ID CHRONIC KIDNEY-DISEASE; PERIPHERAL ARTERIAL-DISEASE; DIABETIC-PATIENTS; SYSTOLIC PRESSURES; LOWER EXTREMITIES; RISK; ASSOCIATION; CALCIFICATION; PREVALENCE; MANAGEMENT AB Background Supra-normal ankle brachial index (ABI) (>1.40), poses diagnostic challenges to determine the presence, location, and severity of peripheral artery disease (PAD). The anatomic distribution of PAD in patients with elevated ABI has not been previously described. Methods A retrospective review of all patients referred to the Massachusetts General Hospital vascular diagnostic laboratory from 5 January 2006 to 12 January 2011 who had both a supra-normal ABI and contrast arteriography (CA) within 3 months of each other is reported. Angiographic patterns were described using the Trans Atlantic Inter Society Consensus II (TASC II) classification. Results One-hundred sixteen limbs were analyzed in 92 patients. Mean age was 71.6 years (+/- 11.2); 81.5% (75/92) were male; 85.9% Caucasian (79/92); 67.4% diabetics (62/92); 78.3% hypertensive (72/92); 67.4% hypercholesterolemic (62/92); and 64.1% were current or former tobacco users (59/92). Chronic hemodialysis was present in 18.5% (17/92) and 15.2% (14/92) received chronic corticosteroids. Intermittent claudication was present in 46.7% (43/92) and critical limb ischemia in 52.2% (48/92). Aortoiliac, femoral and infra-popliteal involvement per angiography occurred in 14.9% (15/101), 56.1% (60/107), and 84.0% (84/100), respectively. Multilevel disease was present in 48.8% (42/86) of patients. PAD was absent in 4.7% (4/86) of patients. Toe brachial index <0.7 was found in 92% (92/100) of patients with angiographically confirmed PAD. Conclusion In symptomatic patients referred to a vascular laboratory who were found to have supra-normal ABI, nearly one half exhibited multilevel PAD, and over 80% had infrapopliteal involvement. A supra-normal ABI in such patients mandates evaluation for the presence and extent of PAD. (c) 2013 Wiley Periodicals, Inc. C1 [Weinberg, Ido; Giri, Jay; Calfon, Marcella A.; Hawkins, Beau M.; Weinberg, Mitchell D.; Margey, Ronan; Hannon, Kathleen; Schainfeld, Robert M.; Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiovasc Med, Sect Vasc Med, Vasc Ctr, Boston, MA 02114 USA. RP Jaff, MR (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM mjaff@partners.org NR 25 TC 9 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY PY 2013 VL 81 IS 6 BP 1025 EP 1030 DI 10.1002/ccd.24604 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 133SN UT WOS:000318160200028 PM 22899598 ER PT J AU Hawkins, BM Drachman, DE AF Hawkins, Beau M. Drachman, Douglas E. TI You can get there from here! A novel virtual 4.5F guide facilitates renal intervention from transradial access SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 [Hawkins, Beau M.; Drachman, Douglas E.] Massachusetts Gen Hosp, Div Cardiol, Vasc Med Sect, Boston, MA 02114 USA. RP Drachman, DE (reprint author), Massachusetts Gen Hosp, Cardiovasc Fellowship Program, 55 Fruit St,Gray Bigelow 800, Boston, MA 02114 USA. EM ddrachman@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY PY 2013 VL 81 IS 6 BP 1047 EP 1048 DI 10.1002/ccd.24923 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 133SN UT WOS:000318160200032 PM 23606498 ER PT J AU Alam, MM Tsai, LL Rollins, SM Sheikh, A Khanam, F Bufano, MK Yu, YA Ying, WF Kalsy, A Sultana, T Abu Sayeed, M Jahan, N LaRocque, RC Harris, JB Leung, DT Brooks, WA Calderwood, SB Charles, RC Qadri, F Ryan, ET AF Alam, Mohammad Murshid Tsai, Lillian L. Rollins, Sean M. Sheikh, Alaullah Khanam, Farhana Bufano, Meagan Kelly Yu, Yanan Ying Wu-Freeman Kalsy, Anuj Sultana, Tania Abu Sayeed, M. Jahan, Nusrat LaRocque, Regina C. Harris, Jason B. Leung, Daniel T. Brooks, W. Abdullah Calderwood, Stephen B. Charles, Richelle C. Qadri, Firdausi Ryan, Edward T. TI Identification of In Vivo-Induced Bacterial Proteins during Human Infection with Salmonella enterica Serotype Paratyphi A SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ANTIGEN TECHNOLOGY IVIAT; ESCHERICHIA-COLI; SEROVAR TYPHI; FIMBRIAL OPERONS; GENE-EXPRESSION; REGULATED GENES; YGGG GENE; TYPHIMURIUM; FEVER; BLOOD AB Salmonella enterica serotype Paratyphi A is a human-restricted pathogen and the cause of paratyphoid A fever. Using a high-throughput immunoscreening technique, in vivo-induced antigen technology (IVIAT), we identified 20 immunogenic bacterial proteins expressed in humans who were bacteremic with S. Paratyphi A but not those expressed in S. Paratyphi A grown under standard laboratory conditions. The majority of these proteins have known or potential roles in the pathogenesis of S. enterica. These include proteins implicated in cell adhesion, fimbrial structure, adaptation to atypical conditions, oxidoreductase activity, proteolysis, antimicrobial resistance, and ion transport. Of particular interest among these in vivo-expressed proteins were S. Paratyphi A (SPA)2397, SPA2612, and SPA1604. SPA2397 and SPA2612 are prophage related, and SPA1604 is in Salmonella pathogenicity island 11 (SPI-11). Using real-time quantitative PCR (RT-qPCR), we confirmed increased levels of mRNA expressed by genes identified by IVIAT in a comparison of mRNA levels in organisms in the blood of bacteremic patients to those in in vitro cultures. Comparing convalescent-to acute-phase samples, we also detected a significant increase in the reaction of convalescent-phase antibodies with two proteins identified by IVIAT:SPA2397 and SPA0489. SPA2397 is a phage-related lysozyme, Gp19, and SPA0489 encodes a protein containing NlpC/P60 and cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domains. In a previous study utilizing a different approach, we found that transcripts for 11 and 7 of the genes identified by IVIAT were detectable in organisms in the blood of humans in Bangladesh who were bacteremic with S. Paratyphi A and Salmonella enterica serovar Typhi, respectively. S. Paratyphi A antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis and might have diagnostic, therapeutic, or preventive relevance. C1 [Alam, Mohammad Murshid; Sheikh, Alaullah; Khanam, Farhana; Sultana, Tania; Abu Sayeed, M.; Jahan, Nusrat; Leung, Daniel T.; Brooks, W. Abdullah; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Alam, Mohammad Murshid; Tsai, Lillian L.; Rollins, Sean M.; Bufano, Meagan Kelly; Yu, Yanan; Ying Wu-Freeman; Kalsy, Anuj; Sultana, Tania; LaRocque, Regina C.; Harris, Jason B.; Leung, Daniel T.; Calderwood, Stephen B.; Charles, Richelle C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rollins, Sean M.; LaRocque, Regina C.; Leung, Daniel T.; Charles, Richelle C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rollins, Sean M.] Fitchburg State Univ, Dept Biol & Chem, Fitchburg, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM etryan@partners.org OI Rollins, Sean/0000-0002-3724-1989; leung, daniel/0000-0001-8401-0801 FU ICDDR,B; National Institutes of Health; National Institute of Allergy and Infectious Diseases [R21 AI100023, U01 AI077883, U01 AI058935]; Training Grant in Vaccine Development and Public Health [D43 TW005572]; Career Development Awards [K01 TW07409, K08 AI089721, K08 AI100923]; American Recovery and Reinvestment Act (ARRA) postdoctoral fellowship in Global Infectious Diseases [TW005572]; Clinical Research Scholars Award [R24 TW007988]; Fogarty International Center; Physician Scientist Early Career Award from the Howard Hughes Medical Institute; Massachusetts General Hospital Physician Scientist Development Award from Massachusetts General Hospital; Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases; Harvard College Program for Research in Science and Engineering Fellowship; iSURF Award from the Harvard Global Health Institute FX This work was supported by the ICDDR,B and by grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (R21 AI100023 and U01 AI077883 to E.T.R. and F.Q., U01 AI058935 to S.B.C., E.T.R., and F.Q., Training Grant in Vaccine Development and Public Health (D43 TW005572 to M.M.A., F.K., A.S., T.S., E.T.R., and F.Q.), Career Development Awards (K01 TW07409 to J.B.H., K08 AI089721 to R.C.C., and K08 AI100923 to D.T.L.), an American Recovery and Reinvestment Act (ARRA) postdoctoral fellowship in Global Infectious Diseases (TW005572 to D.T.L. and R.C.C.), a Clinical Research Scholars Award (R24 TW007988 to S.B.C.) from the Fogarty International Center, a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (to R.C.L.), a Massachusetts General Hospital Physician Scientist Development Award from Massachusetts General Hospital (to R.C.C.), a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases (to D.T.L.), a Harvard College Program for Research in Science and Engineering Fellowship (to L.L.T.), and an iSURF Award from the Harvard Global Health Institute (to L.L.T.). NR 42 TC 6 Z9 6 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2013 VL 20 IS 5 BP 712 EP 719 DI 10.1128/CVI.00054-13 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 133OY UT WOS:000318149500011 PM 23486419 ER PT J AU deLemos, AS Friedman, LS AF deLemos, Andrew S. Friedman, Lawrence S. TI Systemic Causes of Cholestasis SO CLINICS IN LIVER DISEASE LA English DT Article DE Amyloidosis; Cholestasis of sepsis; Congestive hepatopathy; Granulomatous hepatitis; Lymphoma; Sarcoidosis; Sickle cell disease; Total parenteral nutrition ID SICKLE-CELL-DISEASE; BILE-DUCT SYNDROME; INFLAMMATORY-BOWEL-DISEASE; TOTAL PARENTERAL-NUTRITION; PYOGENIC LIVER-ABSCESSES; OF-THE-LITERATURE; SCLEROSING CHOLANGITIS; HEPATOBILIARY TUBERCULOSIS; INTRAHEPATIC CHOLESTASIS; DIABETIC HEPATOSCLEROSIS AB Systemic Causes of Cholestasis Andrew S. deLemos and Lawrence S. Friedman Systemic causes of cholestasis constitute a diverse group of diseases across organ systems. The pathophysiology of cholestasis in systemic disease can be a consequence of direct involvement of a disease process within the liver or extrahepatic biliary system or secondary to immunemediated changes in bile flow. Evaluating a patient with cholestasis for a systemic cause requires an understanding of the patient's risk factors, clinical setting (eg, hospitalized or immunosuppressed patient), clinical features, and pattern of laboratory abnormalities. C1 [deLemos, Andrew S.; Friedman, Lawrence S.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [deLemos, Andrew S.; Friedman, Lawrence S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org FU NIDDK NIH HHS [T32 DK007191] NR 85 TC 5 Z9 5 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1089-3261 J9 CLIN LIVER DIS JI Clin. Liver Dis. PD MAY PY 2013 VL 17 IS 2 BP 301 EP + DI 10.1016/j.cld.2012.11.001 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 135AG UT WOS:000318257800011 PM 23540504 ER PT J AU Blais, MA Malone, JC AF Blais, Mark A. Malone, Johanna C. TI Structure of the DSM-IV Personality disorders as revealed in clinician ratings SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID ASSESSMENT PROCEDURE SWAP; ASSESSING AXIS II; MENTAL-DISORDERS; PROPOSED CHANGES; SAMPLE-SIZE; PART II; DIAGNOSIS; CLASSIFICATION; CRITERIA; UTILITY AB The revisions proposed for the DSM-5 would greatly alter how personality pathology is conceptualized, assessed, and diagnosed. One aspect of the proposed changes, elimination of four current personality disorders, has raised considerable controversy. The present study attempts to inform this debate by exploring clinicians' views of the structure of Personality Disorders using the current diagnostic system, the DSM-W. An exploratory factor analysis was conducted on the DSM-IV Personality Disorder criteria using clinician ratings for 280 patients. The factor analysis revealed eight clear and meaningful factors. The eight factors contained all six personality disorders proposed for retention in DSM-5 but also contained clear representations of two disorders (Paranoid and Schizoid) identified for removal from the system. These conditions appear to have clinical utility and their removal may have unintended negative consequences in clinical practice. Dependent and Avoidant criteria also merged to form a new construct with interesting clinical implications. These findings provide new insights into the complex typologies clinicians employ when applying the DSM-IV system to personality disordered patients. Lastly we argue that successful refinement of clinically significant constructs, like diagnostic systems, requires a balanced appraisal of evidence for clinical utility as well as external and internal validity. (C) 2013 Elsevier Inc. All rights reserved. C1 [Blais, Mark A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Psychol Assessment Ctr, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM Mblais@partners.org NR 44 TC 6 Z9 6 U1 0 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY PY 2013 VL 54 IS 4 BP 326 EP 333 DI 10.1016/j.comppsych.2012.10.014 PG 8 WC Psychiatry SC Psychiatry GA 134FU UT WOS:000318196600003 PM 23219361 ER PT J AU Sun, PZ Wang, Y Xiao, G Wu, RH AF Sun, Phillip Zhe Wang, Yu Xiao, Gang Wu, Renhua TI Simultaneous experimental determination of labile proton fraction ratio and exchange rate with irradiation radio frequency power-dependent quantitative CEST MRI analysis SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE amide proton transfer (APT); chemical exchange saturation transfer (CEST); pH ID SATURATION-TRANSFER CEST; ACUTE CEREBRAL-ISCHEMIA; RF IRRADIATION; CONTRAST AGENTS; PARACEST AGENTS; IN-VIVO; 7 T; PH; RESONANCE; WATER AB Chemical exchange saturation transfer (CEST) imaging is sensitive to dilute proteins/peptides and microenvironmental properties, and has been increasingly evaluated for molecular imaging and in vivo applications. However, the experimentally measured CEST effect depends on the CEST agent concentration, exchange rate and relaxation time. In addition, there may be non-negligible direct radio-frequency (RF) saturation effects, particularly severe for diamagnetic CEST (DIACEST) agents owing to their relatively small chemical shift difference from that of the bulk water resonance. As such, the commonly used asymmetry analysis only provides CEST-weighted information. Recently, it has been shown with numerical simulation that both labile proton concentration and exchange rate can be determined by evaluating the RF power dependence of DIACEST effect. To validate the simulation results, we prepared and imaged two CEST phantoms: a pH phantom of serially titrated pH at a fixed creatine concentration and a concentration phantom of serially varied creatine concentration titrated to the same pH, and solved the labile proton fraction ratio and exchange rate per-pixel. For the concentration phantom, we showed that the labile proton fraction ratio is proportional to the CEST agent concentration with negligible change in the exchange rate. Additionally, we found the exchange rate of the pH phantom is dominantly base-catalyzed with little difference in the labile proton fraction ratio. In summary, our study demonstrated quantitative DIACEST MRI, which remains promising to augment the conventional CEST-weighted MRI analysis. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Sun, Phillip Zhe; Wang, Yu] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sun, Phillip Zhe; Wang, Yu] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Xiao, Gang] Hanshan Normal Univ, Dept Math & Appl Math, Chaozhou, Guangdong, Peoples R China. [Xiao, Gang; Wu, Renhua] Shantou Univ, Coll Med, Affiliated Hosp 2, Dept Radiol, Shantou, Guangdong, Peoples R China. [Xiao, Gang; Wu, Renhua] Prov Key Lab Med Mol Imaging, Shantou, Guangdong, Peoples R China. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu; rhwu@stu.edu.cn FU AHA/SDG [0835384N]; NIH/NIBIB [1K01EB009771]; NSFC [30930027]; [NIH/NCRR-P41RR14075] FX This study was supported in part by grants from AHA/SDG 0835384N, NIH/NIBIB 1K01EB009771, NIH/NCRR-P41RR14075 and NSFC 30930027. NR 50 TC 11 Z9 11 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD MAY-JUN PY 2013 VL 8 IS 3 BP 246 EP 251 DI 10.1002/cmmi.1524 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132BC UT WOS:000318041700005 PM 23606428 ER PT J AU Sharon, VR Armstrong, AW Jim-On, S Ibrahimi, OA Eisen, DB AF Sharon, Victoria R. Armstrong, April W. Jim-On, Shelbi Ibrahimi, Omar A. Eisen, Daniel B. TI Postoperative Preferences in Cutaneous Surgery: A Patient-Centered Investigation From an Academic Dermatologic Surgery Practice SO DERMATOLOGIC SURGERY LA English DT Article AB Background Little is known about postoperative preferences regarding dermatologic surgery. Objective To determine patient preferences for postoperative follow-up after dermatologic surgery, desired follow-up interval, reasons for desired follow-up or lack thereof, and factors that may be associated with these preferences. Materials and Methods Patients who underwent Mohs micrographic surgery or excision within 24months of Mohs micrographic surgery or excision were retrospectively surveyed regarding their postoperative follow-up preferences. Procedure, tumor attributes, complications, and medications were recorded. Results Eighty-nine percent of patients considered postoperative follow-up important, with 55% opting for follow-up within 4weeks and an additional 29.1% within 2 to 3months. After multivariate analyses, there were no significantly associated covariates of interest regarding preference for follow-up. Reasons for desiring follow-up included to ensure the wound healed well (50%), to ensure the cancer had not returned (27.9%), and to examine the rest of the skin (18.6%). Conclusion A majority of patients desired postoperative follow-up visits for a variety of reasons. Anticipation of postoperative concerns should be included in dermatologic surgery planning. C1 [Sharon, Victoria R.; Armstrong, April W.; Jim-On, Shelbi; Eisen, Daniel B.] Univ Calif Davis, Med Ctr, Dept Dermatol, Sacramento, CA 95817 USA. [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT USA. [Ibrahimi, Omar A.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Eisen, DB (reprint author), 3301 C St,Suite 1400, Sacramento, CA 95816 USA. EM dbeisen@ucdavis.edu OI Sharon, Victoria/0000-0002-5108-8757; Eisen, Daniel/0000-0001-6741-3182 NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 2013 VL 39 IS 5 BP 773 EP 778 DI 10.1111/dsu.12136 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 135JL UT WOS:000318284300014 PM 23432932 ER PT J AU Meek, TH Wisse, BE Thaler, JP Guyenet, SJ Matsen, ME Fischer, JD Taborsky, GJ Schwartz, MW Morton, GJ AF Meek, Thomas H. Wisse, Brent E. Thaler, Joshua P. Guyenet, Stephan J. Matsen, Miles E. Fischer, Jonathan D. Taborsky, Gerald J., Jr. Schwartz, Michael W. Morton, Gregory J. TI BDNF Action in the Brain Attenuates Diabetic Hyperglycemia via Insulin-Independent Inhibition of Hepatic Glucose Production SO DIABETES LA English DT Article ID NEUROTROPHIC FACTOR; SYNAPTIC PLASTICITY; ENERGY-BALANCE; MESSENGER-RNA; FOOD-INTAKE; LEPTIN; MICE; RATS; RESISTANCE; OBESITY AB Recent evidence suggests that central leptin administration fully normalizes hyperglycemia in a rodent model of uncontrolled insulin-deficient diabetes by reducing hepatic glucose production (HGP) and by increasing glucose uptake. The current studies were undertaken to determine whether brain-derived neurotrophic factor (BDNF) action in the brain lowers blood glucose in uncontrolled insulin-deficient diabetes and to investigate the mechanisms mediating this effect. Adult male rats implanted with cannulas to either the lateral cerebral ventricle or the ventromedial hypothalamic nucleus (VMN) received either vehicle or sizeptozotocin to induce uncontrolled insulin-deficient diabetes. Three days later, animals received daily intracerebroventricular or intra-VMN injections of either BDNF or its vehicle. We found that repeated daily intracerebroventricular administration of BDNF attenuated diabetic hyperglycemia independent of changes in food intake. Instead, using tracer dilution techniques during a basal clamp, we found that BDNF lowered blood glucose levels by potently suppressing HGP, without affecting tissue glucose uptake, an effect associated with normalization of both plasma glucagon levels and hepatic expression of gluconeogenic genes. Moreover, BDNF microinjection directly into the VMN also lowered fasting blood glucose levels in uncontrolled insulin-deficient diabetes, but this effect was modest compared with intracerebroventricular administration. We conclude that central nervous system BDNF attenuates diabetic hyperglycemia via an insulin-independent mechanism. This action of BDNF likely involves the VMN and is associated with inhibition of glucagon secretion and a decrease in the rate of HGP. Diabetes 62:1512-1518, 2013 C1 [Meek, Thomas H.; Wisse, Brent E.; Thaler, Joshua P.; Guyenet, Stephan J.; Matsen, Miles E.; Fischer, Jonathan D.; Schwartz, Michael W.; Morton, Gregory J.] Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. [Taborsky, Gerald J., Jr.] Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Med Ctr, Seattle, WA USA. RP Morton, GJ (reprint author), Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. EM gjmorton@u.washington.edu FU National Institutes of Health [DK089053, DK083042, DK050154-13]; Nutrition Obesity Research Center (NORC) [DK035816]; University of Washington (Seattle, Washington) [T32 DK0007247]; Perkins Coie; American Heart Association Scientist Development Grant FX This work was supported by National Institutes of Health grants DK089053 (G.J.M.), DK083042 (M.W.S.), and DK050154-13 (G.J.T.); by the Nutrition Obesity Research Center (NORC, DK035816) and the Diabetes and Metabolism Training Grant (T32 DK0007247) at the University of Washington (Seattle, Washington); by research funding from Perkins Coie; and by an American Heart Association Scientist Development Grant (G.J.M.). No other potential conflicts of interest relevant to this article were reported. NR 25 TC 16 Z9 16 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2013 VL 62 IS 5 BP 1512 EP 1518 DI 10.2337/db12-0837 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133HE UT WOS:000318128700030 PM 23274899 ER PT J AU Aguayo-Mazzucato, C Zavacki, AM Marinelarena, A Hollister-Lock, J El Khattabi, I Marsili, A Weir, GC Sharma, A Larsen, PR Bonner-Weir, S AF Aguayo-Mazzucato, Cristina Zavacki, Ann Marie Marinelarena, Alejandra Hollister-Lock, Jennifer El Khattabi, Ilham Marsili, Alessandro Weir, Gordon C. Sharma, Arun Larsen, P. Reed Bonner-Weir, Susan TI Thyroid Hormone Promotes Postnatal Rat Pancreatic beta-Cell Development and Glucose-Responsive Insulin Secretion Through MAFA SO DIABETES LA English DT Article ID EMBRYONIC STEM-CELLS; RECEPTOR ISOFORM; IN-VIVO; ISLETS; GENE; DEIODINASE; EXPRESSION; DIGESTION; ALPHA; MOUSE AB Neonatal beta cells do not secrete glucose-responsive insulin and are considered immature. We previously showed the transcription factor MAFA is key for the functional maturation of beta cells, but the physiological regulators of this process are unknown. Here we show that postnatal rat beta cells express thyroid hormone (TH) receptor isoforms and deiodinases in an age-dependent pattern as glucose responsiveness develops. In vivo neonatal triiodothyronine supplementation and TH inhibition, respectively, accelerated and delayed metabolic development. In vitro exposure of immature islets to triiodothyronine enhanced the expression of Mafa, the secretion of glucose-responsive insulin, and the proportion of responsive cells, all of which are effects that were abolished in the presence of dominant-negative Mafa. Using chromatin immunoprecipitation and electrophoretic mobility shift assay, we show that TH has a direct receptor-ligand interaction with the Mafa promoter and, using a luciferase reporter, that this interaction was functional. Thus, TH can be considered a physiological regulator of functional maturation of beta cells via its induction of Mafa. Diabetes 62:1569-1580, 2013 C1 [Aguayo-Mazzucato, Cristina; Marinelarena, Alejandra; Hollister-Lock, Jennifer; El Khattabi, Ilham; Weir, Gordon C.; Sharma, Arun; Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. [Zavacki, Ann Marie; Marsili, Alessandro; Larsen, P. Reed] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Thyroid Sect, Boston, MA USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. EM susan.bonner-weir@joslin.harvard.edu FU National Institutes of Health [NIH R01 DK 66056, DK 93909, R01 DK 60127, DK 36256, DK 076117, P30 DK36836]; JDRF [1-2011-591]; Diabetes Research and Wellness Foundation; Graetz Fund; Sheenan Family Fellowship; Mary Iaccoca Fellowship; Harvard College Research Program; National Institute of Diabetes and Digestive and Kidney Diseases FX This study was supported by grants from the National Institutes of Health (NIH R01 DK 66056 and DK 93909 [S.B.-W.], R01 DK 60127 [A.S.], DK 36256 [P.R.L.], DK 076117 [A.M.Z.], P30 DK36836 Joslin Diabetes and Endocrinology Research Center (DERC) Advanced Microscopy Core) and by JDRF Grant 1-2011-591 (S.B.-W.). This work was also supported by the Diabetes Research and Wellness Foundation, the Graetz Fund, and an important group of private donors. C.A.-M. was partially supported by the Sheenan Family Fellowship and the Mary Iaccoca Fellowship; A.M. was supported by Harvard College Research Program and the National Institute of Diabetes and Digestive and Kidney Diseases Short-Term Education Program for Underrepresented Persons (STEP-UP). NR 42 TC 38 Z9 40 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2013 VL 62 IS 5 BP 1569 EP 1580 DI 10.2337/db12-0849 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133HE UT WOS:000318128700036 PM 23305647 ER PT J AU Zraika, S Koh, DS Barrow, BM Lu, B Kahn, SE Andrikopoulos, S AF Zraika, Sakeneh Koh, Duk-Su Barrow, Breanne M. Lu, Bao Kahn, Steven E. Andrikopoulos, Sofianos TI Neprilysin Deficiency Protects Against Fat-Induced Insulin Secretory Dysfunction by Maintaining Calcium Influx SO DIABETES LA English DT Article ID PANCREATIC BETA-CELLS; NEUTRAL ENDOPEPTIDASE ACTIVITY; C57BL/6J MICE; MOUSE MODELS; GLUCOSE; ACIDS; INHIBITION; PALMITATE; PATHWAY; ISLETS AB Neprilysin contributes to free fatty acid (FFA)-induced cellular dysfunction in nonislet tissues in type 2 diabetes. Here, we show for the first time that with prolonged FFA exposure, islet neprilysin is upregulated and this is associated with reduced insulin pre-mRNA and ATP levels, oxidative/nitrative stress, impaired potassium and calcium channel activities, and decreased glucose-stimulated insulin secretion (GSLS). Genetic ablation of neprilysin specifically protects against FFA-induced impairment of calcium influx and GSIS in vitro and in vivo but does not ameliorate other FFA-induced defects. Importantly, adenoviral overexpression of neprilysin in islets cultured without FFA reproduces the defects in both calcium influx and GSIS, suggesting that upregulation of neprilysin per se mediates insulin secretory dysfunction and that the mechanism for protection conferred by neprilysin deletion involves prevention of reduced calcium influx. Our findings highlight the critical nature of calcium signaling for normal insulin secretion and suggest that interventions to inhibit neprilysin may improve beta-cell function in obese humans with type 2 diabetes. Diabetes 62:1593-1601, 2013 C1 [Zraika, Sakeneh; Barrow, Breanne M.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Zraika, Sakeneh; Barrow, Breanne M.; Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Koh, Duk-Su] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Lu, Bao] Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp, Boston, MA 02115 USA. [Andrikopoulos, Sofianos] Univ Melbourne, Heidelberg Repatriat Hosp, Dept Med, Heidelberg, Vic, Australia. RP Zraika, S (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. EM zraikas@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health (NIH) [DK-080945]; Department of Veterans Affairs, VA Puget Sound Health Care System; Diabetes Australia Research Trust; National Health and Medical Research Council (NHMRC) of Australia; NIH [DK-017047]; NHMRC of Australia FX This study was supported by National Institutes of Health (NIH) Grant DK-080945 (to S.Z.), the Department of Veterans Affairs, VA Puget Sound Health Care System, the Diabetes Australia Research Trust, and the National Health and Medical Research Council (NHMRC) of Australia. Calcium influx and rubidium efflux studies as well as histological studies were performed at the University of Washington's Diabetes Research Center Cell Function Analysis Core and Cellular and Molecular Imaging Core, respectively, both of which are supported by NIH Grant DK-017047. S.A. was the recipient of a Career Development Award from the NHMRC of Australia. NR 48 TC 4 Z9 4 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2013 VL 62 IS 5 BP 1593 EP 1601 DI 10.2337/db11-1593 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133HE UT WOS:000318128700038 PM 23328128 ER PT J AU Saxena, R Saleheen, D Been, LF Garavito, ML Braun, T Bjonnes, A Young, R Ho, WK Rasheed, A Frossard, P Sim, XL Hassanali, N Radha, V Chidambaram, M Liju, S Rees, SD Ng, DPK Wong, TY Yamauchi, T Hara, K Tanaka, Y Hirose, H McCarthy, MI Morris, AP Basit, A Barnett, AH Katulanda, P Matthews, D Mohan, V Wander, GS Singh, JR Mehra, NK Ralhan, S Kamboh, MI Mulvihill, JJ Maegawa, H Tobe, K Maeda, S Cho, YS Tai, ES Kelly, MA Chambers, JC Kooner, JS Kadowaki, T Deloukas, P Rader, DJ Danesh, J Sanghera, DK AF Saxena, Richa Saleheen, Danish Been, Latonya F. Garavito, Martha L. Braun, Timothy Bjonnes, Andrew Young, Robin Ho, Weang Kee Rasheed, Asif Frossard, Philippe Sim, Xueling Hassanali, Neelam Radha, Venkatesan Chidambaram, Manickam Liju, Samuel Rees, Simon D. Ng, Daniel Peng-Keat Wong, Tien-Yin Yamauchi, Toshimasa Hara, Kazuo Tanaka, Yasushi Hirose, Hiroshi McCarthy, Mark I. Morris, Andrew P. Basit, Abdul Barnett, Anthony H. Katulanda, Prasad Matthews, David Mohan, Viswanathan Wander, Gurpreet S. Singh, Jai Rup Mehra, Narinder K. Ralhan, Sarju Kamboh, M. Ilyas Mulvihill, John J. Maegawa, Hiroshi Tobe, Kazuyuki Maeda, Shiro Cho, Yoon S. Tai, E. Shyong Kelly, M. Ann Chambers, John C. Kooner, Jaspal S. Kadowaki, Takashi Deloukas, Panos Rader, Daniel J. Danesh, John Sanghera, Dharambir K. CA DIAGRAM MuTHER AGEN TI Genome-Wide Association Study Identifies a Novel Locus Contributing to Type 2 Diabetes Susceptibility in Sikhs of Punjabi Origin From India SO DIABETES LA English DT Article ID BODY-MASS INDEX; GAMMA-SARCOGLYCAN; GENOTYPE IMPUTATION; GENETIC-VARIATION; SOUTH-ASIA; COMPLEX; RISK; POPULATIONS; DISEASES; IGF2BP2 AB We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10(-3)) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10(-4)) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 x 10(-8)) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10(-3)) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10(-4)) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10(-5) to < 10(-7)), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis. Diabetes 62:1746-1755, 2013 C1 [Saxena, Richa; Bjonnes, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Saxena, Richa; Bjonnes, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Saleheen, Danish; Rasheed, Asif; Frossard, Philippe] Ctr Noncommunicable Dis, Karachi, Pakistan. [Saleheen, Danish; Young, Robin; Ho, Weang Kee; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Saleheen, Danish] Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA. [Saleheen, Danish] Univ Penn, Dept Epidemiol & Med, Philadelphia, PA 19104 USA. [Been, Latonya F.; Garavito, Martha L.; Braun, Timothy; Mulvihill, John J.; Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA. [Sim, Xueling] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Sim, Xueling] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. [Sim, Xueling] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. [Hassanali, Neelam; McCarthy, Mark I.; Katulanda, Prasad; Matthews, David] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Radha, Venkatesan; Chidambaram, Manickam; Liju, Samuel; Mohan, Viswanathan] Madras Diabet Res Fdn, Madras, Tamil Nadu, India. [Rees, Simon D.; Kelly, M. Ann] Univ Birmingham, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Rees, Simon D.; Barnett, Anthony H.; Kelly, M. Ann] Heart England Natl Hlth Serv Fdn Trust, Ctr Diabet, Birmingham, W Midlands, England. [Ng, Daniel Peng-Keat; Tai, E. Shyong] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Wong, Tien-Yin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Wong, Tien-Yin] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore. [Wong, Tien-Yin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Yamauchi, Toshimasa; Hara, Kazuo; Kadowaki, Takashi] Univ Tokyo, Grad Sch Med, Dept Diabet & Metabol Dis, Tokyo, Japan. [Hara, Kazuo] Univ Tokyo, Century Med & Res Ctr 22, Dept Integrated Mol Sci Metabol Dis, Tokyo, Japan. [Tanaka, Yasushi] St Marianna Univ, Sch Med, Dept Internal Med, Div Endocrinol & Metab, Kanagawa, Japan. [Hirose, Hiroshi] Keio Univ, Ctr Hlth, Sch Med, Tokyo, Japan. [McCarthy, Mark I.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England. [Basit, Abdul] Baqai Inst Diabetol & Endocrinol, Karachi, Pakistan. [Katulanda, Prasad] Univ Colombo, Dept Clin Med, Diabet Res Unit, Colombo, Sri Lanka. [Mohan, Viswanathan] Dr Mohans Diabet Special Ctr, Madras, Tamil Nadu, India. [Wander, Gurpreet S.; Ralhan, Sarju] Hero Dayanand Med Coll & Heart Inst, Ludhiana, Punjab, India. [Singh, Jai Rup] Cent Univ Punjab, Bathinda, Punjab, India. [Mehra, Narinder K.] All India Inst Med Sci & Res, New Delhi, India. [Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Maegawa, Hiroshi] Shiga Univ Med Sci, Dept Med, Shiga, Japan. [Tobe, Kazuyuki] Toyama Univ, Dept Internal Med 1, Toyama 930, Japan. [Maeda, Shiro] RIKEN Ctr Genom Med, Lab Endocrinol & Metab, Kanagawa, Japan. [Cho, Yoon S.] Hallym Univ, Dept Biomed Sci, Chunchon 200702, Gangwon Do, South Korea. [Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. [Tai, E. Shyong] Duke NUS Grad Med Sch Singapore, Singapore, Singapore. [Chambers, John C.; Kooner, Jaspal S.] Ealing Hosp Natl Hlth Serv Trust, Middlesex, England. [Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare Natl Hlth Serv Trust, London, England. [Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, London, England. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England. [Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England. [Rader, Daniel J.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Sanghera, DK (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA. EM dharambir-sanghera@ouhsc.edu RI Deloukas, Panos/B-2922-2013; Altshuler, David/A-4476-2009; Hide, Winston Hide/C-7217-2009; Zondervan, Krina/M-1143-2013; Boehm, Bernhard/F-8750-2015; Meitinger, Thomas/O-1318-2015; Rudan, Igor/I-1467-2012; OI van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Manickam, Chidambaram/0000-0001-8750-8576; Jorgensen, Torben/0000-0001-9453-2830; Tai, E Shyong/0000-0003-2929-8966; Hattersley, Andrew/0000-0001-5620-473X; Deloukas, Panos/0000-0001-9251-070X; Altshuler, David/0000-0002-7250-4107; Hide, Winston Hide/0000-0002-8621-3271; Zondervan, Krina/0000-0002-0275-9905; HO, WEANG KEE/0000-0002-8269-7344; Zeggini, Eleftheria/0000-0003-4238-659X; Kamboh, M. Ilyas/0000-0002-3453-1438; Rudan, Igor/0000-0001-6993-6884; CHANG, TIEN-JYUN/0000-0001-9437-5847 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-082766]; University of Oklahoma Health Sciences Center FX This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK-082766 and a seed grant from the University of Oklahoma Health Sciences Center. NR 55 TC 53 Z9 55 U1 0 U2 27 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2013 VL 62 IS 5 BP 1746 EP 1755 DI 10.2337/db12-1077 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133HE UT WOS:000318128700054 PM 23300278 ER PT J AU Guo, J Song, LG Liu, ML Segawa, H Miyamoto, KI Bringhurst, FR Kronenberg, HM Juppner, H AF Guo, Jun Song, Lige Liu, Minlin Segawa, Hiroko Miyamoto, Ken-Ichi Bringhurst, F. Richard Kronenberg, Henry M. Jueppner, Harald TI Activation of a Non-cAMP/PKA Signaling Pathway Downstream of the PTH/PTHrP Receptor Is Essential for a Sustained Hypophosphatemic Response to PTH Infusion in Male Mice SO ENDOCRINOLOGY LA English DT Article ID NA/P-I-COTRANSPORTER; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; PARATHYROID-HORMONE; PHOSPHOLIPASE-C; PHOSPHATE-TRANSPORT; DOWN-REGULATION; CHONDROCYTE HYPERTROPHY; VITAMIN-D; NAPI-IIA; OK CELLS AB PTH increases urinary Pi excretion by reducing expression of two renal cotransporters [NaPi-IIa (Npt2a) and NaPi-IIc (Npt2c)]. In contrast to acute transporter regulation that is cAMP/protein kinase A dependent, long-term effects require phospholipase C (PLC) signaling by the PTH/PTHrP receptor (PPR). To determine whether the latter pathway regulates Pi through Npt2a and/or Npt2c, wild-type mice (Wt) and animals expressing a mutant PPR incapable of PLC activation (DD) were tested in the absence of one (Npt2a(-/-) or Npt2c(-/-)) or both phosphate transporters (2a/2c-dko). PTH infusion for 8 days caused a rapid and persistent decrease in serum Pi in Wt mice, whereas serum Pi in DD mice fell only transiently for the first 2 days. Consistent with these findings, fractional Pi excretion index was increased initially in both animals, but this increase persisted only when the PPR Wt was present. The hypophosphatemic response to PTH infusion was impaired only slightly in PPR Wt/Npt2c(-/-) or DD/Npt2c(-/-) mice. Despite lower baselines, PTH infusion in PPR Wt/Npt2a(-/-) mice decreased serum Pi further, an effect that was attenuated in DD/Npt2a(-/-) mice. Continuous PTH had no effect on serum Pi in 2a/2c-dko mice. PTH administration increased serum 1,25 dihydroxyvitamin D-3 levels in Wt and DD mice and increased levels above the elevated baseline with ablation of either but not of both transporters. Continuous PTH elevated serum fibroblast growth factor 23 and blood Ca2+ equivalently in all groups of mice. Our data indicate that PLC signaling at the PPR contributes to the long-term effect of PTH on Pi homeostasis but not to the regulation of 1,25 dihydroxyvitamin D-3, fibroblast growth factor 23, or blood Ca2+. (Endocrinology 154: 1680-1689, 2013) C1 [Guo, Jun; Song, Lige; Liu, Minlin; Bringhurst, F. Richard; Kronenberg, Henry M.; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Guo, Jun; Song, Lige; Liu, Minlin; Bringhurst, F. Richard; Kronenberg, Henry M.; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Segawa, Hiroko; Miyamoto, Ken-Ichi] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Mol Nutr, Tokushima 7708504, Japan. RP Guo, J (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM jguo2@partners.org FU National Institutes of Health [PO1 DK11794] FX This work was supported by National Institutes of Health Grant PO1 DK11794. NR 47 TC 14 Z9 14 U1 1 U2 8 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 MAY PY 2013 VL 154 IS 5 BP 1680 EP 1689 DI 10.1210/en.2012-2240 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 130IV UT WOS:000317908800003 PM 23515284 ER PT J AU Hader, WJ Tellez-Zenteno, J Metcalfe, A Hernandez-Ronquillo, L Wiebe, S Kwon, CS Jette, N AF Hader, Walter J. Tellez-Zenteno, Jose Metcalfe, Amy Hernandez-Ronquillo, Lisbeth Wiebe, Samuel Kwon, Churl-Su Jette, Nathalie TI Complications of epilepsy surgery: A systematic review of focal surgical resections and invasive EEG monitoring SO EPILEPSIA LA English DT Article DE Surgical risk; Epilepsy; Mortality; Neurologic deficits ID TEMPORAL-LOBE EPILEPSY; TRIAL AB Purpose Underutilization of epilepsy surgery remains a major problem and is in part due to physicians' misconceptions about the risks associated with epilepsy surgery. The purpose of this study was to systematically review the literature on complications of focal epilepsy surgery. Methods A literature search was conducted using PubMed and Embase to identify studies examining epilepsy surgery complications. Abstract and full text review, along with data extraction, was done in duplicate. Minor medical and neurologic complications were defined as those that resolved completely within 3months of surgery, whereas major complications persisted beyond that time frame. Descriptive statistics were used to report complication proportions. Key Findings Invasive monitoring: Minor complications were reported in 7.7% of patients, whereas major complications were reported in only 0.6% of patients undergoing invasive monitoring. Resective surgery: Minor and major medical complications were reported in 5.1% and 1.5% of patients respectively, most common being cerebrospinal fluid (CSF) leak. Minor neurologic complications occurred in 10.9% of patients and were twice as frequent in children (11.2% vs. 5.5%). Minor visual field defects were most common (12.9%). Major neurologic complications were noted in 4.7% of patients, with the most common being major visual field defects (2.1% overall). Perioperative mortality was uncommon after epilepsy surgery, occurring in only 0.4% of temporal lobe patients (1.2%extratemporal). Significance The majority of complications after epilepsy surgery are minor or temporary as they tend to resolve completely. Major permanent neurologic complications remain uncommon. Mortality as a result of epilepsy surgery in the modern era is rare. C1 [Hader, Walter J.; Metcalfe, Amy; Wiebe, Samuel; Jette, Nathalie] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Tellez-Zenteno, Jose; Hernandez-Ronquillo, Lisbeth] Univ Saskatchewan, Div Neurol, Saskatoon, SK, Canada. [Metcalfe, Amy; Wiebe, Samuel; Jette, Nathalie] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. [Wiebe, Samuel; Jette, Nathalie] Hotchkiss Brain Inst, Calgary, AB, Canada. [Wiebe, Samuel; Jette, Nathalie] Inst Publ Hlth, Calgary, AB, Canada. [Kwon, Churl-Su] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Hader, WJ (reprint author), Foothills Med Ctr, Div Neurosurg, Dept Clin Neurosci, 12th Floor,1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM walter.hader@albertahealthservices.ca RI Hernandez Ronquillo, Lizbeth/J-4826-2015 OI Hernandez Ronquillo, Lizbeth/0000-0001-7057-9343 FU American Epilepsy Society (AES); Milken Family Foundation; Alberta Innovates Health Solutions (AI-HS); Alberta Health Services; Canadian Institutes of Health Research (CIHR); Hotchkiss Brain Institute; University of Calgary; Canada Research Chair in Neurological Health Services Research; Royal University Hospital Foundation in Saskatoon trough the Mudjadik Thyssen Mining Professorship in Neurosciences; University of Saskatchewan; CIHR in Genetics (Ethics, Law, and Society); CIHR strategic training grant studentships in Maternal Fetal Newborn Health and Genetics, Child Development, and Health FX This study was in part supported by a Clinician Scientist award to N. Jette from the American Epilepsy Society (AES) and the Milken Family Foundation and operating grants and or funds from Alberta Innovates Health Solutions (AI-HS), Alberta Health Services, the Canadian Institutes of Health Research (CIHR), the Hotchkiss Brain Institute, and the University of Calgary. N. Jette holds a salary award from AI-HS and a Canada Research Chair in Neurological Health Services Research. S. Wiebe holds the Hopewell Professorship of Clinical Neurosciences Research at the University of Calgary. JF Tellez-Zenteno holds a salary award from the Royal University Hospital Foundation in Saskatoon trough the Mudjadik Thyssen Mining Professorship in Neurosciences and also receives operating funds from the University of Saskatchewan. A. Metcalfe held a doctoral award from CIHR in Genetics (Ethics, Law, and Society) and CIHR strategic training grant studentships in Maternal Fetal Newborn Health and Genetics, Child Development, and Health during this study. NR 16 TC 53 Z9 54 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 MAY PY 2013 VL 54 IS 5 BP 840 EP 847 DI 10.1111/epi.12161 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 134UR UT WOS:000318241000015 PM 23551133 ER PT J AU Feldt-Rasmussen, U Brabant, G Maiter, D Jonsson, B Toogood, A Koltowska-Haggstrom, M Rasmussen, AK Buchfelder, M Saller, B Biller, BMK AF Feldt-Rasmussen, Ulla Brabant, Georg Maiter, Dominique Jonsson, Bjorn Toogood, Andy Koltowska-Haggstrom, Maria Rasmussen, Aase Krogh Buchfelder, Michael Saller, Bernhard Biller, Beverly M. K. TI Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE DEFICIENCY; HYPOTHALAMIC-PITUITARY DISEASE; QUALITY-OF-LIFE; REPLACEMENT THERAPY; HYPOPITUITARY ADULTS; BODY-COMPOSITION; PREMATURE MORTALITY; ENDOCRINE-SOCIETY; DIAGNOSIS; RESPONSIVENESS AB Objective: We studied whether the severity of GH deficiency (GHD) defined as i) GH-peak on stimulation tests (insulin tolerance test (ITT), arginine, and glucagon), ii) number of additional pituitary deficits, or iii) baseline IGF1 SDS could impact the response to GH treatment. We further explored whether iv) IGF1 SDS after 24 months of GH replacement or v) Delta IGF1 SDS from baseline to 24 months was related to the phenotypic response to GH treatment. Design, patients, and measurements: The patient cohort (n=1752; 50% women) was obtained from KIMS (Pfizer International Metabolic Database). The patients were divided into three groups of approximately equal size (tertiles) according to the stimulated GH-peak values and baseline IGF1 SDS and were studied at baseline, 12, and 24 months of GH therapy. Results: Lower baseline IGF1 SDS predicted better response in weight, BMI, total cholesterol, and triglycerides, while IGF1 SDS after 24 months was associated with reduction in waist/hip ratio, total cholesterol, and improved quality of life (QoL). Age-correlated negatively with the response in body weight, BMI, waist, IGF1 SDS, and total and LDL-cholesterol. Response in weight and BMI was greater in men than in women, whereas women showed greater improvement in QoL than men. Patients with more severe GHD as assessed by lower GH-peaks and more pituitary hormone deficiencies had a greater increase in IGF1 SDS. The increase in IGF1 SDS was associated with a reduction in waist/hip ratio and an increase in weight, BMI, and triglycerides. There was no correlation with other lipids, blood pressure, or glucose. Conclusion: Our findings indicate that baseline and 24 months, IGF1 and its degree of increase during GH replacement were more important than stimulated peak GH to predict the phenotypic response. European Journal of Endocrinology 168 733-743 C1 [Feldt-Rasmussen, Ulla; Rasmussen, Aase Krogh] Univ Copenhagen, Natl Univ Hosp, Rigshosp, Dept Med Endocrinol, DK-2100 Copenhagen, Denmark. [Brabant, Georg] Christ Hosp, Dept Endocrinol, Manchester M20 4BX, Lancs, England. [Maiter, Dominique] St Luc Univ Hosp, Dept Endocrinol & Nutr, B-1200 Brussels, Belgium. [Jonsson, Bjorn] Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden. [Toogood, Andy] Univ Hosp Birmingham, NHS Fdn Trust, Dept Endocrinol, Birmingham B15 2TH, W Midlands, England. [Koltowska-Haggstrom, Maria] Pfizer Inc, Sollentuna, Sweden. [Buchfelder, Michael] Univ Erlangen Nurnberg, Dept Neurosurg, D-91045 Erlangen, Germany. [Saller, Bernhard] Pfizer Inc, Tadworth, England. [Biller, Beverly M. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. RP Feldt-Rasmussen, U (reprint author), Univ Copenhagen, Natl Univ Hosp, Rigshosp, Dept Med Endocrinol, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM ufeldt@rh.dk FU Pfizer, Inc.; Novo Nordisk; Pfizer; Merck Serono; Arvid Nilsson's Fund FX G Brabant, B M K Biller, M Buchfelder, U Feldt-Rasmussen, D Maiter, A Toogood, and B Jonsson received consulting fees from Pfizer, Inc. U Feldt-Rasmussen received research funding from Novo Nordisk. B M K Biller received consulting fees from Novo Nordisk and research funding from Novo Nordisk, Pfizer, and Merck Serono. M Koltowska-Haggstrom is an employee of Pfizer, Inc. (Sweden), and B Saller is an employee of Pfizer, Inc. (UK).; Pfizer sponsored the KIMS database. U Feldt-Rasmussen received a research grant from Arvid Nilsson's Fund. Salary for her research time is paid by this fund. No authors were paid for their contributions to this manuscript. NR 45 TC 4 Z9 4 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAY PY 2013 VL 168 IS 5 BP 733 EP 743 DI 10.1530/EJE-13-0005 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131OP UT WOS:000318003300011 PM 23416951 ER PT J AU Sakai, N Chun, J Duffield, JS Wada, T Luster, AD Tager, AM AF Sakai, Norihiko Chun, Jerold Duffield, Jeremy S. Wada, Takashi Luster, Andrew D. Tager, Andrew M. TI LPA(1)-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation SO FASEB JOURNAL LA English DT Article DE lysophosphatidic acid; Rho GTPases; myocardin-related transcription factor-A; myocardin-related transcription factor-B; serum response factor ID TISSUE GROWTH-FACTOR; ENCAPSULATING PERITONEAL SCLEROSIS; TGF-BETA ACTIVATION; PULMONARY-FIBROSIS; MESOTHELIAL CELLS; DIALYSIS PATIENTS; GENE-EXPRESSION; ACTIN DYNAMICS; LUNG FIBROSIS; C-FOS AB There has been much recent interest in lysophosphatidic acid (LPA) signaling through one of its receptors, LPA(1), in fibrotic diseases, but the mechanisms by which LPA-LPA(1) signaling promotes pathological fibrosis remain to be fully elucidated. Using a mouse peritoneal fibrosis model, we demonstrate central roles for LPA and LPA(1) in fibroblast proliferation. Genetic deletion or pharmacological antagonism of LPA(1) protected mice from peritoneal fibrosis, blunting the increases in peritoneal collagen by 65.4 and 52.9%, respectively, compared to control animals and demonstrated that peritoneal fibroblast proliferation was highly LPA(1) dependent. Activation of LPA1 on mesothelial cells induced these cells to express connective tissue growth factor (CTGF), driving fibroblast proliferation in a paracrine fashion. Activation of mesothelial cell LPA(1) induced CTGF expression by inducing cytoskeleton reorganization in these cells, causing nuclear translocation of myocardin-related transcription factor (MRTF)-A and MRTF-B. Pharmacological inhibition of MRTF-induced transcription also diminished CTGF expression and fibrosis in the peritoneal fibrosis model, mitigating the increase in peritoneal collagen content by 57.9% compared to controls. LPA(1)-induced cytoskeleton reorganization therefore makes a previously unrecognized but critically important contribution to the profibrotic activities of LPA by driving MRTF-dependent CTGF expression, which, in turn, drives fibroblast proliferation.-Sakai, N., Chun, J., Duffield, J. S., Wada, T., Luster, A. D., Tager, A. M. LPA(1)-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation. FASEB J. 27, 1830-1846 (2013). www.fasebj.org C1 [Sakai, Norihiko; Luster, Andrew D.; Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Sakai, Norihiko; Luster, Andrew D.; Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. [Chun, Jerold] Scripps Res Inst, Dept Mol Biol, Helen L Dorris Inst Neurol & Psychiat Disorders, La Jolla, CA 92037 USA. [Duffield, Jeremy S.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Duffield, Jeremy S.] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA. [Duffield, Jeremy S.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA. [Wada, Takashi] Kanazawa Univ, Fac Med, Inst Med Pharmaceut & Hlth Sci, Div Nephrol,Dept Lab Med, Kanazawa, Ishikawa, Japan. RP Tager, AM (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Rm 8301, Charlestown, MA 02129 USA. EM amtager@partners.org FU U.S. National Institutes of Health (NIH) [R01-HL095732, R01-HL108975]; Scleroderma Research Foundation; Pulmonary Fibrosis Foundation; Coalition for Pulmonary Fibrosis; Nirenberg Center for Advanced Lung Disease; Japan Society for the Promotion of Science (JSPS) Excellent Young Researcher Overseas Visit Program; NIH [R01-MH051699, R01-DA019674] FX The authors gratefully acknowledge support from U.S. National Institutes of Health (NIH) grants R01-HL095732 and R01-HL108975, and Scleroderma Research Foundation, Pulmonary Fibrosis Foundation, Coalition for Pulmonary Fibrosis, and Nirenberg Center for Advanced Lung Disease grants to A.M.T, the Japan Society for the Promotion of Science (JSPS) Excellent Young Researcher Overseas Visit Program to N.S., and NIH grants R01-MH051699 and R01-DA019674 to J.C. The authors also thank B. A. Fontaine for his expert assistance, and Amira Pharmaceuticals (San Diego, CA, USA) for the kind gift of AM095. The authors declare no conflicts of interest. NR 53 TC 38 Z9 39 U1 0 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2013 VL 27 IS 5 BP 1830 EP 1846 DI 10.1096/fj.12-219378 PG 17 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 134PU UT WOS:000318226100004 PM 23322166 ER PT J AU Nath, AK Roberts, LD Liu, Y Mahon, SB Kim, S Ryu, JH Werdich, A Januzzi, JL Boss, GR Rockwood, GA MacRae, CA Brenner, M Gerszten, RE Peterson, RT AF Nath, Anjali K. Roberts, Lee D. Liu, Yan Mahon, Sari B. Kim, Sonia Ryu, Justine H. Werdich, Andreas Januzzi, James L. Boss, Gerry R. Rockwood, Gary A. MacRae, Calum A. Brenner, Matthew Gerszten, Robert E. Peterson, Randall T. TI Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure SO FASEB JOURNAL LA English DT Article DE mitochondria; inosine; zebrafish; riboflavin ID CYTOCHROME-C-OXIDASE; SODIUM-NITROPRUSSIDE; LIPID-PEROXIDATION; SMALL MOLECULES; DIFFERENT MODES; BILE-ACIDS; INTOXICATION; CELLS; INHIBITION; ZEBRAFISH AB Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.-Nath, A. K., Roberts, L. D., Liu, Y., Mahon, S. B., Kim, S., Ryu, J. H., Werdich, A., Januzzi, J. L., Boss, G. R., Rockwood, G. A., MacRae, C. A., Brenner, M., Gerszten, R. E., Peterson, R. T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. FASEB J. 27, 1928-1938 (2013). www.fasebj.org C1 [Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Kim, Sonia; Ryu, Justine H.; Januzzi, James L.; Gerszten, Robert E.; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Kim, Sonia; Ryu, Justine H.; Januzzi, James L.; Gerszten, Robert E.; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Charlestown, MA USA. [Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Gerszten, Robert E.; Peterson, Randall T.] Broad Inst, Cambridge, MA USA. [Mahon, Sari B.; Brenner, Matthew] Univ Calif Irvine, Irvine Med Ctr, Orange, CA 92668 USA. [Werdich, Andreas; MacRae, Calum A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA. [Boss, Gerry R.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Rockwood, Gary A.] USA, Analyt Toxicol Div, Med Res Inst Chem Def, Aberdeen Proving Ground, MD USA. RP Nath, AK (reprint author), Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM anath@cvrc.mgh.harvard.edu; peterson@cvrc.mgh.harvard.edu OI Roberts, Lee/0000-0002-1455-5248 FU U.S. National Institutes of Health (NIH) grant [T32 HL-007208]; NIH Countermeasures Against Chemical Threats (Counter ACT) [U54NS063718, U54NS079201]; CounterACT Program, NIH Office of the Director; National Institute of Allergy and Infectious Diseases, NIH/U.S. Army Medical Research and Materiel Command [Y1-OD-9611-01/A120-B.P2009-1] FX Funding for this project has been provided by U.S. National Institutes of Health (NIH) grant T32 HL-007208 (A.K.N. and Y.L.) and NIH Countermeasures Against Chemical Threats (Counter ACT) grants U54NS063718 and U54NS079201 (S.B.M. and M.B.) and U54NS079201 (R.T.P). The zebrafish research was supported, in part, by the CounterACT Program, NIH Office of the Director, and the National Institute of Allergy and Infectious Diseases, NIH/U.S. Army Medical Research and Materiel Command interagency agreement no. Y1-OD-9611-01/A120-B.P2009-1 (G.A.R.). NR 54 TC 12 Z9 13 U1 2 U2 28 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAY PY 2013 VL 27 IS 5 BP 1928 EP 1938 DI 10.1096/fj.12-225037 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 134PU UT WOS:000318226100013 PM 23345455 ER PT J AU Montgomery, SB Goode, DL Kvikstad, E Albers, CA Zhang, ZDD Mu, XJ Ananda, G Howie, B Karczewski, KJ Smith, KS Anaya, V Richardson, R Davis, J MacArthur, DG Sidow, A Duret, L Gerstein, M Makova, KD Marchini, J McVean, G Lunter, G AF Montgomery, Stephen B. Goode, David L. Kvikstad, Erika Albers, Cornelis A. Zhang, Zhengdong D. Mu, Xinmeng Jasmine Ananda, Guruprasad Howie, Bryan Karczewski, Konrad J. Smith, Kevin S. Anaya, Vanessa Richardson, Rhea Davis, Joe MacArthur, Daniel G. Sidow, Arend Duret, Laurent Gerstein, Mark Makova, Kateryna D. Marchini, Jonathan McVean, Gil Lunter, Gerton CA 1000 Genomes Project Consortium TI The origin, evolution, and functional impact of short insertion-deletion variants identified in 179 human genomes SO GENOME RESEARCH LA English DT Article ID RECOMBINATION HOT-SPOTS; STRAND BREAK REPAIR; STRUCTURAL VARIATION; DNA; MICROSATELLITE; GENE; REARRANGEMENTS; INSTABILITY; MECHANISM; POPULATION AB Short insertions and deletions (indels) are the second most abundant form of human genetic variation, but our understanding of their origins and functional effects lags behind that of other types of variants. Using population-scale sequencing, we have identified a high-quality set of 1.6 million indels from 179 individuals representing three diverse human populations. We show that rates of indel mutagenesis are highly heterogeneous, with 43%-48% of indels occurring in 4.03% of the genome, whereas in the remaining 96% their prevalence is 16 times lower than SNPs. Polymerase slippage can explain upwards of three-fourths of all indels, with the remainder being mostly simple deletions in complex sequence. However, insertions do occur and are significantly associated with pseudo-palindromic sequence features compatible with the fork stalling and template switching (FoSTeS) mechanism more commonly associated with large structural variations. We introduce a quantitative model of polymerase slippage, which enables us to identify indel-hypermutagenic protein-coding genes, some of which are associated with recurrent mutations leading to disease. Accounting for mutational rate heterogeneity due to sequence context, we find that indels across functional sequence are generally subject to stronger purifying selection than SNPs. We find that indel length modulates selection strength, and that indels affecting multiple functionally constrained nucleotides undergo stronger purifying selection. We further find that indels are enriched in associations with gene expression and find evidence for a contribution of nonsense-mediated decay. Finally, we show that indels can be integrated in existing genome-wide association studies (GWAS); although we do not find direct evidence that potentially causal protein-coding indels are enriched with associations to known disease-associated SNPs, our findings suggest that the causal variant underlying some of these associations may be indels. C1 [Montgomery, Stephen B.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Montgomery, Stephen B.; Smith, Kevin S.; Anaya, Vanessa; Richardson, Rhea; Sidow, Arend] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Montgomery, Stephen B.; Goode, David L.; Karczewski, Konrad J.; Davis, Joe; Sidow, Arend] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Kvikstad, Erika; Duret, Laurent] Univ Lyon 1, CNRS, INRIA, Lab Biometrie & Biol Evolut,UMR5558, F-69622 Villeurbanne, France. [Albers, Cornelis A.; MacArthur, Daniel G.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Albers, Cornelis A.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Zhang, Zhengdong D.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Mu, Xinmeng Jasmine; Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Ananda, Guruprasad; Makova, Kateryna D.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Howie, Bryan] Univ Chicago, Dept Stat, Chicago, IL 60637 USA. [MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Marchini, Jonathan; McVean, Gil] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Kvikstad, Erika; McVean, Gil; Lunter, Gerton] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. RP Montgomery, SB (reprint author), Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. EM smontgom@stanford.edu; gerton.lunter@well.ox.ac.uk RI Albers, Kees/A-4170-2015; Lunter, Gerton/H-4939-2016; Mu, Xinmeng/P-2562-2016; OI Albers, Kees/0000-0003-4115-3727; Mu, Xinmeng/0000-0002-8079-0828; Duret, Laurent/0000-0003-2836-3463; McVean, Gil/0000-0002-5012-4162; Lunter, Gerton/0000-0002-3798-2058; Karczewski, Konrad/0000-0003-2878-4671; Clarke, Laura/0000-0002-5989-6898 FU NSF [DBI-0965596]; NIH [R01GM087472]; British Heart Foundation [RG/09/12/28096]; EMBO [ALTF 354-2010]; Wellcome Trust [090532/Z/09/Z]; Edward J. Mallinckrodt Jr. Foundation FX This research was supported in part by NSF grant DBI-0965596 (to K.D.M.), NIH grant R01GM087472 (to K.D.M. and Kristin Eckert), British Heart Foundation grant RG/09/12/28096 (to C.A.A.), EMBO Long Term Fellowship ALTF 354-2010 (to E.K.), Wellcome Trust core grant 090532/Z/09/Z (G.L. and G.McV.), and the Edward J. Mallinckrodt Jr. Foundation (S.B.M.). S.B.M. would like to thank Emmanouil T. Dermitzakis for his support of this work. NR 48 TC 73 Z9 73 U1 3 U2 29 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 MAY PY 2013 VL 23 IS 5 BP 749 EP 761 DI 10.1101/gr.148718.112 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 134IA UT WOS:000318202400001 PM 23478400 ER PT J AU Zhou, XB Qiu, WL Sathirapongsasuti, JF Cho, MH Mancini, JD Lao, TT Thibault, DM Litonjua, AA Bakke, PS Gulsvik, A Lomas, DA Beaty, TH Hersh, CP Anderson, C Geigenmuller, U Raby, BA Rennard, SI Perrella, MA Choi, AMK Quackenbush, J Silverman, EK AF Zhou, Xiaobo Qiu, Weiliang Sathirapongsasuti, J. Fah Cho, Michael H. Mancini, John D. Lao, Taotao Thibault, Derek M. Litonjua, Augusto A. Bakke, Per S. Gulsvik, Amund Lomas, David A. Beaty, Terri H. Hersh, Craig P. Anderson, Christopher Geigenmuller, Ute Raby, Benjamin A. Rennard, Stephen I. Perrella, Mark A. Choi, Augustine M. K. Quackenbush, John Silverman, Edwin K. TI Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells SO GENOMICS LA English DT Article DE Hedgehog interacting protein (HHIP); Gene expression profiling; COPD (Chronic obstructive pulmonary disease); Extracellular matrix (ECM); Network modeling ID OBSTRUCTIVE PULMONARY-DISEASE; GENOME-WIDE ASSOCIATION; SURROGATE VARIABLE ANALYSIS; CIGARETTE-SMOKE; BINDING PROTEIN; LUNG-CANCER; RECK; REGULATOR; COPD; IDENTIFICATION AB Hedgehog interacting protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis. (c) 2013 Elsevier Inc. All rights reserved. C1 [Zhou, Xiaobo; Qiu, Weiliang; Cho, Michael H.; Mancini, John D.; Lao, Taotao; Thibault, Derek M.; Litonjua, Augusto A.; Hersh, Craig P.; Anderson, Christopher; Geigenmuller, Ute; Raby, Benjamin A.; Silverman, Edwin K.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Zhou, Xiaobo; Cho, Michael H.; Litonjua, Augusto A.; Hersh, Craig P.; Raby, Benjamin A.; Perrella, Mark A.; Choi, Augustine M. K.; Silverman, Edwin K.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Zhou, Xiaobo; Qiu, Weiliang; Cho, Michael H.; Mancini, John D.; Lao, Taotao; Thibault, Derek M.; Litonjua, Augusto A.; Hersh, Craig P.; Anderson, Christopher; Geigenmuller, Ute; Raby, Benjamin A.; Perrella, Mark A.; Choi, Augustine M. K.; Silverman, Edwin K.] Harvard Univ, Sch Med, Boston, MA USA. [Sathirapongsasuti, J. Fah; Quackenbush, John] Dana Faber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Sathirapongsasuti, J. Fah; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bakke, Per S.; Gulsvik, Amund] Univ Bergen, Dept Thorac Med, Bergen, Norway. [Gulsvik, Amund] Univ Bergen, Dept Resp Med, Bergen, Norway. [Bakke, Per S.; Gulsvik, Amund] Haukeland Hosp, N-5021 Bergen, Norway. [Lomas, David A.] Univ Cambridge, Dept Med, Cambridge Inst Med Res, Cambridge CB2 2QQ, England. [Beaty, Terri H.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Rennard, Stephen I.] Nebraska Med Ctr, Omaha, NE USA. [Perrella, Mark A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Zhou, XB (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. EM Xiaobo.zhou@channing.harvard.edu; ed.silverman@channing.harvard.edu OI Qiu, Weiliang/0000-0002-9155-6957; Litonjua, Augusto/0000-0003-0422-5875 FU U.S. National Institutes of Health (NIH) [R01 HL075478, R01 HL084323, P01 HL083069, P01 HL105339, U01 HL089856, U01 HL089897, P01 H105339]; National Heart, Lung, and Blood Institute [N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, N01HR76119]; Centers for Medicare and Medicaid Services; Agency for Healthcare Research and Quality; Cooperative Studies Program/ERIC of the US Department of Veterans Affairs; GlaxoSmithKline; COPD Foundation; National Heart, Lung, and Blood Institute (NHLBI) FX This work was supported by the U.S. National Institutes of Health (NIH) grants R01 HL075478, R01 HL084323, P01 HL083069, P01 HL105339, U01 HL089856 (Silverman), U01 HL089897, and P01 H105339. The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute, the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality. The Normative Aging Study is supported by the Cooperative Studies Program/ERIC of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). The Norway GenKOLS study (Genetics of Chronic Obstructive Lung Disease, GSK code RES11080), the ECLIPSE study (clinicaltrials.gov identifier NCT00292552; GSK code SCO104960) and the ICGN study are funded by GlaxoSmithKline. The COPDGene project is also supported by the COPD Foundation through contributions made by an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer and Sunovion. This study used biological specimens and data provided by the Lung Tissue Research Consortium (LTRC) supported by the National Heart, Lung, and Blood Institute (NHLBI).; The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute contracts N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118 and N01HR76119. NR 50 TC 18 Z9 18 U1 2 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2013 VL 101 IS 5 BP 263 EP 272 DI 10.1016/j.ygeno.2013.02.010 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 132HD UT WOS:000318057600001 PM 23459001 ER PT J AU Diver, E O'Connor, O Garrett, L Boruta, D Goodman, A Del Carmen, M Schorge, J Mueller, P Growdon, W AF Diver, Elisabeth O'Connor, Owen Garrett, Leslie Boruta, David Goodman, Annekathryn Del Carmen, Marcela Schorge, John Mueller, Peter Growdon, Whitfield TI Modest benefit of total parenteral nutrition and chemotherapy after venting gastrostomy tube placement SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Bowel obstruction; TPN; Chemotherapy ID MALIGNANT BOWEL OBSTRUCTION; PERITONEAL CANCER INDEX; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; ADVANCED OVARIAN-CANCER; GYNECOLOGICAL MALIGNANCY; INTESTINAL-OBSTRUCTION; EXPERIENCE; CARCINOMA; SURVIVAL; SURGERY AB Objective. The aim of the study is to review a single institution's experience with gastrostomy tubes (GTs) performed for malignant bowel obstruction from gynecologic cancers. Methods. Women with gynecologic cancers who underwent venting GT placement from 2000 to 2008 were identified and clinical data were extracted. Logistic regression and spearman correlational coefficients were used to determine relationships between variables. Survival analysis was performed using the Kaplan-Meier method and a Cox proportional hazard model. Results. We identified 115 women who underwent GT placement, the majority of whom were diagnosed with ovarian cancer (84%). Median time from cancer diagnosis to GT placement was 2.2 years. Median survival following GT placement was 5.6 weeks. A majority (56%) developed GT complications requiring GT revision. While burden of disease as assessed on CT scan by the validated peritoneal cancer index (PCI) was not associated with survival, low CA-125 within one week of GT placement was associated with improved survival (p<0.01). TPN was administered in 36% of women, was associated with concurrent chemotherapy (p<0.001) and a 5 week survival benefit (p<0.01). Chemotherapy after GT was administered in 40% of women and was associated with a 10 week survival benefit (p<0.001). Age-adjusted multivariate analysis identified chemotherapy as the only independent variable associated with survival. Conclusions. Women with malignant bowel obstructions from gynecologic cancers requiring palliative GT placement had a guarded prognosis measured in weeks. Gastrostomy tubes near the end of life had a high rate of complications requiring medical intervention. Chemotherapy after GT was associated with TPN administration, and both were associated with a modest extension in survival. (C) 2013 Elsevier Inc. All rights reserved. C1 [Diver, Elisabeth; Garrett, Leslie; Boruta, David; Goodman, Annekathryn; Del Carmen, Marcela; Schorge, John; Growdon, Whitfield] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept OB GYN,Div Gynecol Oncol, Boston, MA 02114 USA. [O'Connor, Owen; Mueller, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Intervent Radiol, Boston, MA 02114 USA. [Diver, Elisabeth; O'Connor, Owen; Garrett, Leslie; Boruta, David; Goodman, Annekathryn; Del Carmen, Marcela; Schorge, John; Mueller, Peter; Growdon, Whitfield] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Growdon, W (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 55 Fruit St,Yawkey Ctr Outpatient Care 9E, Boston, MA 02114 USA. EM ediver@partners.org; owen.oconnor7@gmail.com; lgarret1@bidmc.harvard.edu; dboruta@partners.org; agoodman@partners.org; mdelcarmen@partners.org; jschorge@partners.org; pmueller@partners.org; wgrowdon@partners.org NR 17 TC 7 Z9 7 U1 1 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 MAY PY 2013 VL 129 IS 2 BP 332 EP 335 DI 10.1016/j.ygyno.2013.02.002 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 132HN UT WOS:000318058600011 PM 23402902 ER PT J AU Gerace, M Liu, B Kushak, R Grabowski, E AF Gerace, M. Liu, B. Kushak, R. Grabowski, E. TI Shiga toxin-1 and TNF alpha does not change tissue factor co-localization with tissue factor pathway inhibitor on human umbilical vein endothelial cells SO HAEMOPHILIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2013 VL 19 IS 3 BP 466 EP 467 PG 2 WC Hematology SC Hematology GA 132OM UT WOS:000318078400068 ER PT J AU Gulur, P Buonanno, FS AF Gulur, Padma Buonanno, Ferdinando S. TI Intracranial Hypotension Caused by Anterior Cervical CSF Alleviated by an Epidural Blood Patch SO HEADACHE LA English DT Article DE cerebrospinal fluid; epidural blood patch; headache ID CEREBROSPINAL-FLUID LEAK AB We present a case in which a thoracocervical epidural blood patch was used to treat an anteriorly situated cerebrospinal fluid leak following 2 failed blood patches in the lumbar region. The challenge in identifying the source of the leak, deteriorating health of the patient, and risks from the procedure, contributes to the uniqueness of this case. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 2013 VL 53 IS 5 BP 838 EP 841 DI 10.1111/head.12051 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 134VN UT WOS:000318243800014 PM 23405991 ER PT J AU O'Neal, RL Nam, KT LaFleur, BJ Barlow, B Nozaki, K Lee, HJ Kim, WH Yang, HK Shi, CJ Maitra, A Montgomery, E Washington, MK El Rifai, W Drapkin, RI Goldenring, JR AF O'Neal, Ryan L. Nam, Ki Taek LaFleur, Bonnie J. Barlow, Brittney Nozaki, Koji Lee, Hyuk-Joon Kim, Woo Ho Yang, Han-Kwang Shi, Chanjuan Maitra, Anirban Montgomery, Elizabeth Washington, M. Kay El Rifai, Wael Drapkin, Ronny I. Goldenring, James R. TI Human epididymis protein 4 is up-regulated in gastric and pancreatic adenocarcinomas SO HUMAN PATHOLOGY LA English DT Article DE WFDC2; HE4; Metaplasia; Adenocarcinoma ID INTRAEPITHELIAL NEOPLASIA; PROGNOSTIC-SIGNIFICANCE; OVARIAN-CANCER; CELLS; HE-4; CARCINOMAS; DRIVEN; MODEL AB Upper gastrointestinal neoplasia in the esophagus, stomach, and pancreas is associated with the formation of preneoplastic metaplasias. We have previously reported the up-regulation of human epididymis protein 4 (HE4) in all metaplasias in the stomach of humans and mice. We have now sought to evaluate the expression of HE4 in metaplasias/preneoplastic precursors and cancers of the human stomach, pancreas, and esophagus. Tissue microarrays for gastric cancers, pancreatic cancers, and esophageal adenocarcinoma were stained with antibodies against HE4. Immunostaining was quantified by digital imaging, and the results were evaluated to assess the expression in metaplasias, the expression in cancer pathological subtypes, and the effects of expression on survival in patients with cancer. In patients with gastric cancer from Korea, HE4 was detected in 74% of intestinal and 90% of diffuse cancers, whereas in a gastric cancer cohort from Johns Hopkins, HE4 was detected in 74% of intestinal-type and 92% of diffuse cancers. Nevertheless, in both cohorts, there was no impact of HE4 expression on overall survival. In the esophagus, we observed the expression of HE4 in scattered endocrine cells within Barrett esophagus samples, but Barrett columnar metaplasias and HE4 were detected in only 2% of esophageal adenocarcinomas. Finally, in the pancreas, HE4 expression was not observed in pancreatic intraepithelial neoplasia lesions, but 46.8% of pancreatic adenocarcinomas expressed HE4. Still, we did not observe any influence of HE4 expression on survival. The results suggest that HE4 is up-regulated during gastric and pancreatic carcinogenesis. (C) 2013 Elsevier Inc. All rights reserved. C1 [O'Neal, Ryan L.; Nam, Ki Taek; Goldenring, James R.] Vanderbilt Univ, Sch Med, Nashville VA Med Ctr, Nashville, TN 37232 USA. [O'Neal, Ryan L.; Nam, Ki Taek; Barlow, Brittney; El Rifai, Wael; Goldenring, James R.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37232 USA. [O'Neal, Ryan L.; Nam, Ki Taek; Barlow, Brittney; Goldenring, James R.] Vanderbilt Univ, Sch Med, Epithelia Biol Ctr, Nashville, TN 37232 USA. [O'Neal, Ryan L.; Nam, Ki Taek; Barlow, Brittney; Goldenring, James R.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [LaFleur, Bonnie J.] Univ Arizona, Div Epidemiol & Biostat, Tucson, AZ 85724 USA. [Nozaki, Koji] Univ Tokyo, Dept Gastrointestinal Surg, Tokyo, Japan. [Lee, Hyuk-Joon; Yang, Han-Kwang] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Kim, Woo Ho] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. [Shi, Chanjuan; Maitra, Anirban; Montgomery, Elizabeth] Johns Hopkins Univ, Inst Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21205 USA. [Shi, Chanjuan; Washington, M. Kay] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. [El Rifai, Wael] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA. [Drapkin, Ronny I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Goldenring, James R.] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. RP Goldenring, JR (reprint author), Vanderbilt Univ, Sch Med, Epithelia Biol Ctr, 10435-G MRB 4,2213 Garland Ave, Nashville, TN 37232 USA. EM jim.goldenring@vanderbilt.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU NIH [RO1 DK071590, U01 CA152990]; ARRA [RO1 DK071590-S1]; Department of Veterans Affairs FX These studies were supported by grants from NIH RO1 DK071590 (J.R.G.), as well as ARRA Supplemental Funding from RO1 DK071590-S1, a Merit Review Award from the Department of Veterans Affairs, and funding from NIH U01 CA152990 (R.D.). This work was supported by core resources of the Vanderbilt Digestive Disease Center (P30 DK058404), the Vanderbilt SPORE in Gastrointestinal Cancer Tissue Core (P50 CA095103), the Vanderbilt Epithelial Biology Center, and the Vanderbilt-Ingram Cancer Center. NR 21 TC 12 Z9 13 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2013 VL 44 IS 5 BP 734 EP 742 DI 10.1016/j.humpath.2012.07.017 PG 9 WC Pathology SC Pathology GA 134HQ UT WOS:000318201400007 PM 23084584 ER PT J AU Biscuola, M Van de Vijver, K Castilla, MA Romero-Perez, L Lopez-Garcia, MA Diaz-Martin, J Matias-Guiu, X Oliva, E Calvo, JP AF Biscuola, Michele Van de Vijver, Koen Angeles Castilla, Maria Romero-Perez, Laura Angeles Lopez-Garcia, Maria Diaz-Martin, Juan Matias-Guiu, Xavier Oliva, Esther Palacios Calvo, Jose TI Oncogene alterations in endometrial carcinosarcomas SO HUMAN PATHOLOGY LA English DT Article DE Endometrial carcinosarcomas; Oncogenes; Predictive markers ID UTERINE SEROUS CARCINOMA; MOLECULAR ALTERATIONS; TISSUE MICROARRAYS; TARGETED THERAPIES; C-KIT; EXPRESSION; MUTATIONS; EGFR; SARCOMAS; PIK3CA AB Endometrial carcinosarcomas are aggressive neoplasias composed of high-grade carcinomatous and sarcomatous elements. The pathogenesis and specific genetic alterations underlying these tumors are still not well known. We analyzed alterations in oncogenes involved in the pathogenesis of endometrial carcinomas that might represent predictive markers for specific therapies. Immunohistochemistry for HER2 (tyrosine kinase-type cell surface receptor HER2) and c-KIT (tyrosine-protein kinase Kit) and fluorescence in situ hybridization for EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma receptor tyrosine kinase) were carried out for 76 endometrial carcinosarcoma samples on sequential tissue microarray sections. Analysis of 238 mutations across 19 common oncogenes was performed on 34 samples using the Sequenom OncoCarta Panel (Sequenom, Hamburg, Germany). We observed EGFR, HER2, and c-KIT expression in 71%, 1.5%, and 2.7% of tumors, respectively. EGFR amplification was detected in 11 of 76 endometrial carcinosarcomas (14.5%). Four samples showed both amplification and aneuploidy (5.2%). ALK amplification together with chromosome 2 polysomy was found in 1.3% of endometrial carcinosarcomas. In total, 23 mutations in 9 different oncogenes were detected in 15 (44.1%) of 34 endometrial carcinosarcomas. Five endometrial carcinosarcomas (14.7%) had 2 or more mutations. Eleven tumors (32.3%) had mutations affecting the PI3K (phosphoinositide-3-kinase)/AKT (v-akt murine thymoma viral oncogene homolog 1) (6 mutations in PIK3CA (PI3K catalytic alpha polypeptide) and 1 in AKT) and/or RAS/BRAF (serine/threonine-protein kinase B-rat) pathway (3 KRAS [kirsten RAS oncogene homolog], 2 NRAS [neuroblastoma RAS viral oncogene homolog], and 1 BRAF). Mutations in PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) and/or KIT were found in 5 endometrial carcinosarcomas (14.7%). Finally, we found mutations in MET (met proto-oncogene [hepatocyte growth factor receptor]) in 2 tumors (5.9%) and in EGFR in one (2.9%). Our study evidences mutations in oncogenes in endometrial carcinosarcomas that are targets or modulators of response to specific therapies in other human cancers, with PI3IC/AKT being the most frequently altered pathway. (C) 2013 Elsevier Inc. All rights reserved. C1 [Biscuola, Michele; Angeles Castilla, Maria; Romero-Perez, Laura; Angeles Lopez-Garcia, Maria; Diaz-Martin, Juan; Palacios Calvo, Jose] Univ Seville, Hosp Univ Virgen del Rocio, CSIC, Dept Pathol,Inst Biomed Sevilla IBiS, Seville 41013, Spain. [Van de Vijver, Koen; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Matias-Guiu, Xavier] Univ Lleida, Dept Pathol & Mol Genet, Hosp Univ Arnau de Vilanova, IRBLLEIDA, Lleida 25198, Spain. [Palacios Calvo, Jose] Hosp Univ Ramon Y Cajal, Dept Pathol, Madrid 28031, Spain. RP Calvo, JP (reprint author), Hosp Univ Ramon Y Cajal, Dept Pathol, Madrid 28031, Spain. EM eoliva@partners.org; jose.palacios@salud.madrid.org RI Romero-Perez, Laura/C-8314-2015; Castilla, M Angeles/C-9454-2015; Diaz-Martin, Juan/F-4765-2015; IBIS, SARCOMAS/O-1893-2015; matias-guiu, xavier/C-3039-2009 OI Romero-Perez, Laura/0000-0003-3196-4382; matias-guiu, xavier/0000-0002-7201-6605 FU Instituto de Salud Carlos III (ISCIII) [PI07/90324, PI080971]; Junta de Andalucia (Consejeria de Salud) [PI-0384/2007, PI0581/2009]; Consejeria de Innovacion (Proyecto de Excelencia) [P07-CVI-03100]; ISCIII-Red de Biobancos [RD09/0076/00085]; ISCIII [RD06/0020/0013]; Consejeria de Salud, Junta de Andalucia [PI0581/2009]; PFIS fellowship [F109/00193]; [FISPI10/00922]; [2009SGR794]; [RD06/0020/134] FX This work was supported by grants from the Instituto de Salud Carlos III (ISCIII; grant nos. PI07/90324 and PI080971); the Junta de Andalucia (Consejeria de Salud, grant no. PI-0384/2007, PI0581/2009) and the Consejeria de Innovacion (Proyecto de Excelencia, grant no. P07-CVI-03100) to J. P.; grants FISPI10/00922, 2009SGR794, and RD06/0020/134 to X. M. G.; M. B. is a researcher funded by the ISCIII-Red de Biobancos RD09/0076/00085. M. A. C. and J. D. are PhD researchers funded by the ISCIII (grant no. RD06/0020/0013) and the Consejeria de Salud, Junta de Andalucia (PI0581/2009), respectively. L. R. P. is a PhD student recipient of a PFIS fellowship (grant no. F109/00193). NR 35 TC 3 Z9 4 U1 0 U2 14 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 MAY PY 2013 VL 44 IS 5 BP 852 EP 859 DI 10.1016/j.humpath.2012.07.027 PG 8 WC Pathology SC Pathology GA 134HQ UT WOS:000318201400021 PM 23199529 ER PT J AU Oliva, E Pinheiro, NF Heney, NM Kaufman, DS Shipley, WU Gurski, C Spicer, B Paner, GP Gown, AM Amin, MB AF Oliva, Esther Pinheiro, Nathanael F. Heney, Niall M. Kaufman, Donald S. Shipley, William U. Gurski, Carol Spicer, Beverly Paner, Gladell P. Gown, Allen M. Amin, Mahul B. TI Immunohistochemistry as an adjunct in the differential diagnosis of radiation-induced atypia versus urothelial carcinoma in situ of the bladder: a study of 45 cases SO HUMAN PATHOLOGY LA English DT Article DE Urothelial carcinoma in situ; Radiation changes; CK20; p53; CD44s; Differential diagnosis ID URINARY-BLADDER; SELECTIVE BLADDER; NONNEOPLASTIC UROTHELIUM; PROTEIN EXPRESSION; P53 PROTEIN; CYTOKERATIN-20; CANCER; GRADE; KI-67; IMMUNOREACTIVITY AB Muscle invasive urothelial carcinoma has been treated with cystectomy adjuvant therapy. Recently, a bladder-sparing protocol has been offered to selected patients closely followed with surveillance biopsies. In this setting, radiation-induced changes (RAD-Ch) may be very difficult to distinguish from carcinoma in situ, and failing to recognize them may lead to overtreatment. We ascertained the role of immunohistochemistry using cytokeratin (CK) 20, p53, and CD44s in bladder biopsies from 28 patients with a history of bladder radiation and 17 with carcinoma in situ without radiation. Negative or weak multifocal nuclear p53 staining was seen in 24 of 28 RAD-Ch cases, whereas strong and diffuse nuclear p53 staining was found in 8 of 17 carcinoma in situ cases and moderate and focal to multifocal in 3. CK20 showed strong cytoplasmic staining of only umbrella cells in 22 of 28 RAD-Ch cases. In contrast, 11 of 17 carcinomas in situ showed diffuse and strong CK20 positivity and 5 moderate and focal to multifocal positivity. All carcinomas in situ with weak or no p53 showed significant CK20 staining except 1. CD44s displayed diffuse membranous positivity in 7 of 17 RAD-Ch cases and up to mid-third in 8. Only 1 of 17 carcinomas in situ had diffuse membranous CD44s staining. Diffuse and significant CK20 expression was seen in most carcinomas in situ. Strong and diffuse p53 expression was only seen in carcinoma in situ (similar to 50%), whereas diffuse CD44s staining was typically only seen in RAD-Ch. Our data suggest that a CK20(-) p53(-) CD44a panel proves to be very helpful (CK20 more reliable than p53 or CD44s) in the diagnosis of RAD-Ch. (C) 2013 Elsevier Inc. All rights reserved. C1 [Oliva, Esther; Pinheiro, Nathanael F.; Heney, Niall M.; Kaufman, Donald S.; Shipley, William U.; Gurski, Carol; Spicer, Beverly] Massachusetts Gen Hosp, Boston, MA 02118 USA. [Paner, Gladell P.; Amin, Mahul B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Gown, Allen M.] PhenoPath Labs, Seattle, WA USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Pathol Dept Warren 2, 55 Fruit St, Boston, MA 02118 USA. EM eoliva@partners.org NR 36 TC 3 Z9 3 U1 0 U2 1 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 MAY PY 2013 VL 44 IS 5 BP 860 EP 866 DI 10.1016/j.humpath.2012.08.011 PG 7 WC Pathology SC Pathology GA 134HQ UT WOS:000318201400022 PM 23199526 ER PT J AU Merritt, MA De Pari, M Vitonis, AF Titus, LJ Cramer, DW Terry, KL AF Merritt, M. A. De Pari, M. Vitonis, A. F. Titus, L. J. Cramer, D. W. Terry, K. L. TI Reproductive characteristics in relation to ovarian cancer risk by histologic pathways SO HUMAN REPRODUCTION LA English DT Article DE ovarian cancer; histology; reproduction; risk factors; type I; II ID CLEAR-CELL CARCINOMA; SEROUS CARCINOMA; INCESSANT OVULATION; FALLOPIAN-TUBE; EPIDEMIOLOGIC EVIDENCE; GENE-MUTATIONS; UNITED-STATES; MATERNAL RISK; ENDOMETRIOSIS; ARID1A AB Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification? Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer. Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways. This casecontrol study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews. Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers license and town resident lists and were frequency matched with the cases based on age and study center. We used polytomous logistic regression to estimate odds ratios (ORs) and 95 confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR 1.92, 95 CI: 1.362.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (3 versus 0 children, OR 0.15, 95 CI: 0.110.21), having a previous tubal ligation (OR 0.40, 95 CI: 0.260.60) and more weakly hysterectomy (OR 0.71, 95 CI: 0.451.13). In analyses of histologic pathways, parity (3 versus 0 children, OR 0.13, 95 CI: 0.100.18) and having a previous tubal ligation (OR 0.41, 95 CI: 0.280.60) or hysterectomy (OR 0.54, 95 CI: 0.340.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR 2.41, 95 CI: 1.783.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility. A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study. This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types. This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare. Not applicable. C1 [Merritt, M. A.; Cramer, D. W.; Terry, K. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Merritt, M. A.; De Pari, M.; Vitonis, A. F.; Cramer, D. W.; Terry, K. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol,OB GYN Epidemiol Ctr, Boston, MA 02115 USA. [Merritt, M. A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Titus, L. J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. RP Merritt, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM merritt@jimmy.harvard.edu FU National Cancer Institute; NIH [R01CA54419, P50CA105009, R25CA098566]; Department of Defense [W81XWH-10-1-0280]; Ovarian Cancer Research Fund Liz Tilberis Scholar Award; Department of Defense Ovarian Cancer Research Program; Ovarian Cancer Research Fund FX This research was funded by the National Cancer Institute, NIH grants R01CA54419, P50CA105009 and R25CA098566, the Department of Defense grant W81XWH-10-1-0280 and the Ovarian Cancer Research Fund Liz Tilberis Scholar Award.; This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare. NR 59 TC 27 Z9 27 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 2013 VL 28 IS 5 BP 1406 EP 1417 DI 10.1093/humrep/des466 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 133AD UT WOS:000318108900029 PM 23315066 ER PT J AU Havulinna, AS Kettunen, J Ukkola, O Osmond, C Eriksson, JG Kesaniemi, YA Jula, A Peltonen, L Kontula, K Salomaa, V Newton-Cheh, C AF Havulinna, Aki S. Kettunen, Johannes Ukkola, Olavi Osmond, Clive Eriksson, Johan G. Kesaniemi, Y. Antero Jula, Antti Peltonen, Leena Kontula, Kimmo Salomaa, Veikko Newton-Cheh, Christopher TI A Blood Pressure Genetic Risk Score Is a Significant Predictor of Incident Cardiovascular Events in 32 669 Individuals SO HYPERTENSION LA English DT Article DE blood pressure; cardiovascular disease; genetic risk score; genetics; hypertension; prospective cohort study ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; HOSPITAL DISCHARGE REGISTER; HYPERTENSION; VARIANTS; STROKE; METAANALYSIS; LOCI AB Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32 669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2295 incident CVD events occurred. We created GRSs separately for systolic BP and diastolic BP by multiplying the risk allele count of each single nucleotide polymorphism by the effect size estimated in published genome-wide association studies. We performed Cox regression analyses with and without adjustment for clinical factors, including BP at baseline in each cohort. The results were combined by inverse variance-weighted fixed-effects meta-analysis. The GRSs were strongly associated with systolic BP and diastolic BP, and baseline hypertension (all P<10(-62)). Hazard ratios comparing the highest quintiles of systolic BP and diastolic BP GRSs with the lowest quintiles after adjustment for age, age squared, and sex were 1.25 (1.07-1.46; P=0.006) and 1.23 (1.05-1.43; P=0.01), respectively, for incident coronary heart disease; 1.24 (1.01-1.53; P=0.04) and 1.35 (1.09-1.66; P=0.005), respectively, for incident stroke; and 1.23 (1.08-1.40; P=2x10(-6)) and 1.26 (1.11-1.44; P=5x10(-4)), respectively, for composite CVD. In conclusion, BP findings from genome-wide association studies are strongly replicated. GRSs comprising bona fide BP-single nucleotide polymorphisms predicted CVD risk, consistent with a lifelong effect on BP of these variants collectively. (Hypertension. 2013; 61: 987-994.) circle Online Data Supplement C1 [Havulinna, Aki S.; Kettunen, Johannes; Eriksson, Johan G.; Jula, Antti; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England. [Kettunen, Johannes; Peltonen, Leena] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Ukkola, Olavi; Kesaniemi, Y. Antero] Univ Oulu, Dept Med, Inst Clin Med, Oulu, Finland. [Ukkola, Olavi; Kesaniemi, Y. Antero] Oulu Univ Hosp, Clin Res Ctr, Oulu, Finland. [Osmond, Clive] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Kontula, Kimmo] Univ Helsinki, Dept Med, Helsinki, Finland. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA. EM veikko.salomaa@thl.fi; cnewtoncheh@chgr.mgh.harvard.edu OI Eriksson, Johan/0000-0002-2516-2060 FU National Institute for Health and Welfare; Academy of Finland [129 494, 139 635, 129 255, 126 775, 135 072]; National Institute for Health and Welfare (THL); Finnish Center for Pensions (ETK); Social Insurance Institution of Finland (KELA); Local Government Pensions Institution (KEVA); Finnish Foundation for Cardiovascular Research; Finnish Diabetes Research Society; Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska Lakaresallskapet; Signe and Ane Gyllenberg Foundation; Ahokas Foundation; Juho Vainio Foundation; Sigrid Juselius Foundation; Burroughs Wellcome Fund; National Institutes of Health [HL098283] FX FINRISK was mainly funded by the National Institute for Health and Welfare. Additional support was obtained from the Academy of Finland (grant numbers 129 494 and 139 635) to Dr Salomaa. The Health 2000 Study is funded by the National Institute for Health and Welfare (THL), the Finnish Center for Pensions (ETK), The Social Insurance Institution of Finland (KELA), The Local Government Pensions Institution (KEVA), and other organizations listed on the website of the survey (http://www.terveys2000.fi). The OPERA study was supported by the Finnish Foundation for Cardiovascular Research. The Helsinki Birth Cohort Study has been supported by grants to Dr Eriksson from the Academy of Finland (Grant numbers 129 255, 126 775, 135 072), the Finnish Diabetes Research Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation, Ahokas Foundation, and Juho Vainio Foundation. Dr Kontula was supported by the Sigrid Juselius Foundation and the Finnish Foundation for Cardiovascular Research. Dr Newton-Cheh and the SNP genotyping were supported by the Burroughs Wellcome Fund and the National Institutes of Health (HL098283). NR 26 TC 24 Z9 25 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2013 VL 61 IS 5 BP 987 EP + DI 10.1161/HYPERTENSIONAHA.111.00649 PG 21 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127SG UT WOS:000317718200024 PM 23509078 ER PT J AU Lieb, W Jansen, H Loley, C Pencina, MJ Nelson, CP Newton-Cheh, C Kathiresan, S Reilly, MP Assimes, TL Boerwinkle, E Hall, AS Hengstenberg, C Laaksonen, R McPherson, R Thorsteinsdottir, U Ziegler, A Peters, A Thompson, JR Konig, IR Erdmann, J Samani, NJ Vasan, RS Schunkert, H AF Lieb, Wolfgang Jansen, Henning Loley, Christina Pencina, Michael J. Nelson, Christopher P. Newton-Cheh, Christopher Kathiresan, Sekar Reilly, Muredach P. Assimes, Themistocles L. Boerwinkle, Eric Hall, Alistair S. Hengstenberg, Christian Laaksonen, Reijo McPherson, Ruth Thorsteinsdottir, Unnur Ziegler, Andreas Peters, Annette Thompson, John R. Koenig, Inke R. Erdmann, Jeanette Samani, Nilesh J. Vasan, Ramachandran S. Schunkert, Heribert CA CARDIoGRAM TI Genetic Predisposition to Higher Blood Pressure Increases Coronary Artery Disease Risk SO HYPERTENSION LA English DT Article DE blood pressure; coronary artery disease; genetics; polymorphism ID GENOME-WIDE ASSOCIATION; REGRESSION DILUTION; HEART-DISEASE; FOLLOW-UP; HYPERTENSION; METAANALYSIS; LOCI; PHENOTYPES; DESIGN; TRIALS AB Hypertension is a risk factor for coronary artery disease. Recent genome-wide association studies have identified 30 genetic variants associated with higher blood pressure at genome-wide significance (P<5x10(-8)). If elevated blood pressure is a causative factor for coronary artery disease, these variants should also increase coronary artery disease risk. Analyzing genome-wide association data from 22 233 coronary artery disease cases and 64 762 controls, we observed in the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) consortium that 88% of these blood pressure-associated polymorphisms were likewise positively associated with coronary artery disease, that is, they had an odds ratio >1 for coronary artery disease, a proportion much higher than expected by chance (P=4x10(-5)). The average relative coronary artery disease risk increase per each of the multiple blood pressure-raising alleles observed in the consortium was 3.0% for systolic blood pressure-associated polymorphisms (95% confidence interval, 1.8%-4.3%) and 2.9% for diastolic blood pressure-associated polymorphisms (95% confidence interval, 1.7%-4.1%). In substudies, individuals carrying most systolic blood pressure-and diastolic blood pressure-related risk alleles (top quintile of a genetic risk score distribution) had 70% (95% confidence interval, 50%-94%) and 59% (95% confidence interval, 40%-81%) higher odds of having coronary artery disease, respectively, as compared with individuals in the bottom quintile. In conclusion, most blood pressure-associated polymorphisms also confer an increased risk for coronary artery disease. These findings are consistent with a causal relationship of increasing blood pressure to coronary artery disease. Genetic variants primarily affecting blood pressure contribute to the genetic basis of coronary artery disease. (Hypertension. 2013; 61: 995-1001.) circle Online Data Supplement C1 [Lieb, Wolfgang] Univ Clin Schleswig Holstein, Inst Epidemiol, Campus Kiel, Germany. [Jansen, Henning; Hengstenberg, Christian; Schunkert, Heribert] Deutsch Herzzentrum Munich, D-80636 Munich, Germany. [Jansen, Henning; Hengstenberg, Christian; Schunkert, Heribert] Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany. [Loley, Christina; Ziegler, Andreas; Koenig, Inke R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Loley, Christina; Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [Ziegler, Andreas; Erdmann, Jeanette] DZHK German Ctr Cardiovasc Res, Lubeck, Germany. [Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res, Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England. [Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Kathiresan, Sekar] Broad Inst Harvard & Massachusetts Inst Technol M, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Inst Mol Med, Houston, TX USA. [Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Div Epidemiol, Multidisciplinary Cardiovasc Res Ctr, Leeds LS2 9JT, W Yorkshire, England. [Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland. [McPherson, Ruth] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [Thorsteinsdottir, Unnur] DeCODE Genet, Reykjavik, Iceland. [Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Peters, Annette] Munich Heart Alliance, Munich, Germany. [Ziegler, Andreas] Zentrum Klin Studien, Lubeck, Germany. RP Schunkert, H (reprint author), Deutsch Herzzentrum Munich, Lazarettstr 36, D-80636 Munich, Germany. EM schunkert@dhm.mhn.de RI Erdmann, Jeanette/P-7513-2014; Altshuler, David/A-4476-2009; Schreiber, Stefan/B-6748-2008; Laaksonen, Reijo/D-6323-2014; Willenborg, Christina/D-2668-2012; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015; Peters, Annette/A-6117-2011; Konig, Inke/A-4544-2009; Lieb, Wolfgang/C-1990-2012 OI Erdmann, Jeanette/0000-0002-4486-6231; Ziegler, Andreas/0000-0002-8386-5397; Kleber, Marcus/0000-0003-0663-7275; Altshuler, David/0000-0002-7250-4107; Ramachandran, Vasan/0000-0001-7357-5970; Schreiber, Stefan/0000-0003-2254-7771; Willenborg, Christina/0000-0001-5217-6882; Gudnason, Vilmundur/0000-0001-5696-0084; FU EU [LSHM-CT-2006-037593]; ENGAGE; BMBF [FKZ: 01GS0831, NO1-HC-25195]; BMBF; DZHK (German Center for Cardiovascular Research); BMBF (German Ministry of Education and Research) FX This work was supported by the EU-funded Integrated Projects Cardiogenics (LSHM-CT-2006-037593) and ENGAGE as well as the BMBF-funded German National Genome Network (NGFN-Plus) Project Atherogenomics (FKZ: 01GS0831). W. Lieb has in part been supported by the BMBF-funded (federal ministry for education and research) project GANI_MED. There was support also by the DZHK (German Center for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research and by the Framingham core contract NO1-HC-25195. Information regarding the CARDIoGRAM members, acknowledgments, funding sources, and disclosures are detailed in the in the online-only Data Supplement. NR 29 TC 31 Z9 31 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2013 VL 61 IS 5 BP 995 EP + DI 10.1161/HYPERTENSIONAHA.111.00275 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127SG UT WOS:000317718200025 PM 23478099 ER PT J AU Raman, SB Nguyen, MH Cheng, SJ Badrane, H Iczkowski, KA Wegener, M Gaffen, SL Mitchell, AP Clancy, CJ AF Raman, Suresh B. Nguyen, M. Hong Cheng, Shaoji Badrane, Hassan Iczkowski, Kenneth A. Wegener, Marilyn Gaffen, Sarah L. Mitchell, Aaron P. Clancy, Cornelius J. TI A Competitive Infection Model of Hematogenously Disseminated Candidiasis in Mice Redefines the Role of Candida albicans IRS4 in Pathogenesis SO INFECTION AND IMMUNITY LA English DT Article ID MIXED INFECTIONS; HYPHAL FORMATION; ALBICANS; VIRULENCE; CASPOFUNGIN; BLOOD; HOMEOSTASIS; EXPRESSION; RESISTANCE; MUTATIONS AB Candida albicans IRS4 encodes a protein that regulates phosphatidylinositol-(4,5)-bisphosphate, which was shown to contribute to hematogenously disseminated candidiasis (DC) after several days in the standard mouse model. Our objective was to more accurately define the temporal contributions of IRS4 to pathogenesis. During competition assays in vitro, an irs4-null (Delta irs4) mutant exhibited wild-type fitness. In DC experiments, mice were infected intravenously with the Delta irs4 mutant, strain CAI-12 (1 x 10(5) CFU), or a mixture of the strains (0.5 x 10(5) CFU each). In single-strain infections, quantitative PCR revealed reduced Delta irs4 mutant burdens within kidneys at days 1, 4, and 7 but not 6 h. In competitive infections, the Delta irs4 mutant was outcompeted by CAI-12 in each mouse at >= 6 h (competitive indices, P <= 0.0001). At 4 and 7 days, the Delta irs4 mutant burdens during competitive infections were significantly lower than those during single-strain infections (P = 0.01 and P < 0.001, respectively), suggesting increased susceptibility to inflammatory responses. Phagocytic infiltration of kidneys in response to CAI-12 or competitive infections was significantly greater than that in response to Delta irs4 mutant infection at days 1 and 4 (P < 0.001), and the Delta irs4 mutant was more susceptible to phagocytosis and killing by human polymorphonuclear cells (P = 0.01 and P = 0.006, respectively) and mouse macrophages in vitro (P = 0.04 and P = 0.01, respectively). Therefore, IRS4 contributes to tissue invasion at early stages of DC and mediates resistance to phagocytosis as DC progresses. Microarray analysis revealed remarkably similar gene expression by the Delta irs4 mutant and reference strain CAI-12 within blood, suggesting that IRS4 is not significantly involved in the hematogenous stage of disease. A competitive DC model detects attenuated virulence that is not evident with the standard model. C1 [Raman, Suresh B.; Nguyen, M. Hong; Cheng, Shaoji; Badrane, Hassan; Gaffen, Sarah L.; Clancy, Cornelius J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Wegener, Marilyn; Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Iczkowski, Kenneth A.] Univ Colorado, Dept Pathol, Denver, CO 80202 USA. [Mitchell, Aaron P.] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM cjc76@pitt.edu OI Mitchell, Aaron/0000-0002-0868-4000 FU NIDCR NIH HHS [R01 DE022550] NR 31 TC 4 Z9 5 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2013 VL 81 IS 5 BP 1430 EP 1438 DI 10.1128/IAI.00743-12 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 126AE UT WOS:000317582700006 PM 23429534 ER PT J AU Han, XZ Lin, XP Yu, XQ Lin, J Kawai, T LaRosa, KB Taubman, MA AF Han, Xiaozhe Lin, Xiaoping Yu, Xiaoqian Lin, Jiang Kawai, Toshihisa LaRosa, Karen B. Taubman, Martin A. TI Porphyromonas gingivalis Infection-Associated Periodontal Bone Resorption Is Dependent on Receptor Activator of NF-kappa B Ligand SO INFECTION AND IMMUNITY LA English DT Article ID T-CELLS; OSTEOPROTEGERIN LIGAND; IMMUNE-SYSTEM; OSTEOCLAST DIFFERENTIATION; LYMPHOCYTE DEVELOPMENT; RHEUMATOID-ARTHRITIS; POSTMENOPAUSAL WOMEN; DISEASE; OSTEOIMMUNOLOGY; INDUCTION AB Porphyromonas gingivalis is one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-kappa B ligand (RANKL) in P. gingivalis infection-associated periodontal bone resorption. Inbred female Rowett rats were infected orally on four consecutive days (days 0 to 3) with 1 x 10(9) P. gingivalis bacteria (strain ATCC 33277). Separate groups of rats also received an injection of anti-RANKL antibody, osteoprotegerin fusion protein (OPG-Fc), or a control fusion protein (L6-Fc) into gingival papillae in addition to P. gingivalis infection. Robust serum IgG and salivary IgA antibody (P<0.01) and T cell proliferation (P<0.05) responses to P. gingivalis were detected at day 7 and peaked at day 28 in P. gingivalis-infected rats. Both the concentration of soluble RANKL (sRANKL) in rat gingival tissues (P<0.01) and periodontal bone resorption (P<0.05) were significantly elevated at day 28 in the P. gingivalis-infected group compared to levels in the uninfected group. Correspondingly, RANKL-expressing T and B cells in rat gingival tissues were significantly increased at day 28 in the P. gingivalis-infected group compared to the levels in the uninfected group (P<0.01). Injection of anti-RANKL antibody (P<0.05) or OPG-Fc (P<0.01), but not L6-Fc, into rat gingival papillae after P. gingivalis infection resulted in significantly reduced periodontal bone resorption. This study suggests that P. gingivalis infection-associated periodontal bone resorption is RANKL dependent and is accompanied by increased local infiltration of RANKL-expressing T and B cells. C1 [Han, Xiaozhe; Lin, Xiaoping; Yu, Xiaoqian; Lin, Jiang; Kawai, Toshihisa; LaRosa, Karen B.; Taubman, Martin A.] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. [Lin, Xiaoping] China Med Univ, Shengjing Hosp, Dept Stomatol, Shenyang, Liaoning Provin, Peoples R China. [Yu, Xiaoqian] Peking Univ, Dept Periodontol, Sch Stomatol, Beijing 100871, Peoples R China. [Yu, Xiaoqian] Hosp Stomatol, Beijing, Peoples R China. [Lin, Jiang] Harbin Med Univ, Coll 4, Dept Stomatol, Harbin, Peoples R China. RP Han, XZ (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. EM xhan@forsyth.org FU NIH from the National Institute of Dental and Craniofacial Research [DE-03420, DE-07327] FX This work was supported by NIH grants DE-03420 and DE-07327 from the National Institute of Dental and Craniofacial Research. NR 35 TC 20 Z9 22 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2013 VL 81 IS 5 BP 1502 EP 1509 DI 10.1128/IAI.00043-13 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 126AE UT WOS:000317582700013 PM 23439308 ER PT J AU Liu, ZF Ren, C Jones, W Chen, P Seminara, SB Chan, YM Smith, NF Covey, JM Wang, J Chan, KK AF Liu, Zhongfa Ren, Chen Jones, William Chen, Ping Seminara, Stephanie B. Chan, Yee-Ming Smith, Nicola F. Covey, Joseph M. Wang, Jeffrey Chan, Kenneth K. TI LC-MS/MS quantification of a neuropeptide fragment kisspeptin-10 (NSC 741805) and characterization of its decomposition product and pharmacokinetics in rats SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Kisspeptin-10; LC-MS/MS; Pharmacokinetics; Metabolites ID METASTASIS-SUPPRESSOR GENE; PROTEIN-COUPLED RECEPTOR; PITUITARY-GONADAL AXIS; HORMONE-RELEASE; KISS-1 PEPTIDE; GPR54; ACTIVATION; HUMANS; LIGAND AB The kisspeptins are critical regulators of mammalian reproduction. Kisspeptin-10 ((45)YNWNSFGLRF-NH254, kisspeptin-112-121 or metastin 45-54, NSC 741805), an active fragment of kisspeptin, has been shown to be a potent stimulator of gonadotropin-releasing hormone and secretion of luteinizing hormone in both rodents and primates. This shorter peptide fragment may have clinical utility potential and it is important to characterize its pharmacokinetic property. Recently, the pharmacokinetics of both kisspeptin-54 and kisspeptin-10 were characterized in humans using a radioimmunoassay (RIA), which measures only the immunoreactive kisspeptin (kisspeptin-IR). In this study, a highly sensitive and specific LC-MS/MS assay was developed to quantify kisspeptin-10 levels in rat plasma. The lower limit of quantitation (LLOQ) was 0.5 ng/mL, the within-day and between-day coefficient of variations (CVs) ranged from 5.2 to 15.4% and 1.3 to 14.2%, and the accuracy values ranged from 98 to 114% and 99 to 105%, respectively. With this method, stability studies demonstrated that kisspeptin-10 degraded rapidly with decomposition half-lives of 6.8 min, 2.9 min and 1.7 min at 4 degrees C, 25 degrees C, and 37 degrees C, respectively. The principal decomposition product was characterized as the N-terminal tyrosine deleted kisspeptin-10 (46)NWDSFGLRF-NH254. Pharmacokinetic study in rats showed that low ng/mL kisspeptin-10 was detected in the first few minutes, and eliminated rapidly and became undetectable 30 min after intravenous (i.v.) bolus administration of 1.0 mg/kg kisspeptin-10. (C) 2013 Elsevier B.V. All rights reserved. C1 [Liu, Zhongfa; Ren, Chen; Jones, William; Chen, Ping; Chan, Kenneth K.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. [Seminara, Stephanie B.; Chan, Yee-Ming; Chan, Kenneth K.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [Seminara, Stephanie B.; Chan, Yee-Ming; Chan, Kenneth K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Smith, Nicola F.; Covey, Joseph M.] NCI, Rockville, MD 20852 USA. [Liu, Zhongfa; Ren, Chen; Jones, William; Chen, Ping; Seminara, Stephanie B.; Chan, Yee-Ming; Smith, Nicola F.; Covey, Joseph M.; Wang, Jeffrey; Chan, Kenneth K.] Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. [Wang, Jeffrey] Western Univ Hlth Sci, Coll Pharm, Pomona, CA 91766 USA. RP Chan, KK (reprint author), Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 USA. EM chan.56@osu.edu RI Liu, Zhongfa/G-8549-2013 FU NIH-RAID program; NICHD; NIDDK under the National Cancer Institute (NCI) [N01-CM-52205] FX This research was supported by the NIH-RAID program, NICHD and NIDDK under the National Cancer Institute (NCI) contract N01-CM-52205. NR 18 TC 6 Z9 7 U1 0 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 1 PY 2013 VL 926 BP 1 EP 8 DI 10.1016/j.jchromb.2013.02.027 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 131NQ UT WOS:000318000800001 PM 23524040 ER PT J AU Hong, TS AF Hong, Theodore S. TI Radiotherapy for Hepatocellular Carcinoma With Tumor Vascular Thrombus: Ready for Prime Time? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Hong, TS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 8 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2013 VL 31 IS 13 BP 1619 EP + DI 10.1200/JCO.2012.48.2703 PG 3 WC Oncology SC Oncology GA 133PU UT WOS:000318152200007 PM 23547073 ER PT J AU Bower, JE Ganz, PA Irwin, MR Castellon, S Arevalo, J Cole, SW AF Bower, Julienne E. Ganz, Patricia A. Irwin, Michael R. Castellon, Steven Arevalo, Jesusa Cole, Steven W. TI Cytokine Genetic Variations and Fatigue Among Patients With Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; QUALITY-OF-LIFE; INFLAMMATORY BIOMARKERS; BEHAVIORAL SYMPTOMS; PERSISTENT FATIGUE; SLEEP DISTURBANCE; SURVIVORS; POLYMORPHISMS; DEPRESSION AB Purpose Fatigue is a common adverse effect of cancer treatment and may persist for years after treatment completion. However, risk factors for post-treatment fatigue have not been determined. On the basis of studies suggesting an inflammatory basis for fatigue, this study tested the hypothesis that expression-regulating polymorphisms in proinflammatory cytokine genes would predict post-treatment fatigue in breast cancer survivors. Patients and Methods Women diagnosed with early-stage breast cancer (n = 171) completed questionnaires to assess fatigue and other behavioral symptoms (ie, depressive symptoms, memory complaints, sleep disturbance) and provided blood for genotyping within 3 months after primary treatment. Genomic DNA was extracted from peripheral-blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in the promoter regions of three cytokine genes: ILB -511 C>T (rs16944), IL6 -174 G > C (rs1800795), and TNF -308 G > A (rs1800629). An additive genetic risk score was computed by summing the number of high-expression alleles (zero, one, or two) across all three polymorphisms. Results The genetic risk index was significantly associated with fatigue; as the number of high-expression alleles increased, so did self-reported fatigue severity (P = .002). Analyses of individual SNPs showed that TNF -308 and IL6 - 174 were independently associated with fatigue (P = .032). The genetic risk index was also associated with depressive symptoms (P = .007) and memory complaints (P = .016). Conclusion These findings further implicate inflammatory processes as contributors to cancer-related fatigue and suggest a new strategy for identifying and treating patients at risk for this symptom based on genetic variants in proinflammatory cytokine genes. J Clin Oncol 31: 1656-1661. (C) 2013 by American Society of Clinical Oncology C1 [Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Castellon, Steven; Arevalo, Jesusa; Cole, Steven W.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Castellon, Steven] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Bower, JE (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall, Los Angeles, CA 90095 USA. EM jbower@ucla.edu RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU National Institutes of Health [R01-CA109650, R01-CA116778, R01-AG034588, R01-AG026364, R01-CA160245-01, R01-CA119159, R01-HL095799, R01-DA032922-01, P30-AG028748]; Cousins Center for Psychoneuroimmunology; Breast Cancer Research Foundation FX Supported by National Institutes of Health Grants No. R01-CA109650 (P.A.G.), R01-CA116778 (S.W.C.), R01-AG034588, R01-AG026364, R01-CA160245-01, R01-CA119159, R01-HL095799, R01-DA032922-01, and P30-AG028748 (M.I.); the Cousins Center for Psychoneuroimmunology; and the Breast Cancer Research Foundation. NR 59 TC 43 Z9 44 U1 1 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2013 VL 31 IS 13 BP 1656 EP + DI 10.1200/JCO.2012.46.2143 PG 7 WC Oncology SC Oncology GA 133PU UT WOS:000318152200013 PM 23530106 ER PT J AU Ayas, M Saber, W Davies, SM Harris, RE Hale, GA Socie, G LeRademacher, J Thakar, M Deeg, HJJ Al-Seraihy, A Battiwalla, M Camitta, BM Olsson, R Bajwa, RS Bonfim, CM Pasquini, R MacMillan, ML George, B Copelan, EA Wirk, B Al Jefri, A Fasth, AL Guinan, EC Horn, BN Lewis, VA Slavin, S Stepensky, P Bierings, M Gale, RP AF Ayas, Mouhab Saber, Wael Davies, Stella M. Harris, Richard E. Hale, Gregory A. Socie, Gerard LeRademacher, Jennifer Thakar, Monica Deeg, H. Joachim J. Al-Seraihy, Amal Battiwalla, Minoo Camitta, Bruce M. Olsson, Richard Bajwa, Rajinder S. Bonfim, Carmem M. Pasquini, Ricardo MacMillan, Margaret L. George, Biju Copelan, Edward A. Wirk, Baldeep Al Jefri, Abdullah Fasth, Anders L. Guinan, Eva C. Horn, Biljana N. Lewis, Victor A. Slavin, Shimon Stepensky, Polina Bierings, Marc Gale, Robert Peter TI Allogeneic Hematopoietic Cell Transplantation for Fanconi Anemia in Patients With Pretransplantation Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; LOW-DOSE CYCLOPHOSPHAMIDE; UNRELATED DONORS; SIBLING DONOR; RISK-FACTOR; FLUDARABINE; REGISTRY; CANCER; EXPERIENCE; GRAFT AB Purpose Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. Patients and Methods We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Results Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (<= v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (<= v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. Conclusion Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival. J Clin Oncol 31: 1669-1676. (C) 2013 by American Society of Clinical Oncology C1 [Ayas, Mouhab; Al-Seraihy, Amal; Al Jefri, Abdullah] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Saber, Wael; LeRademacher, Jennifer] Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA. [Thakar, Monica] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Camitta, Bruce M.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA. [Camitta, Bruce M.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Davies, Stella M.; Harris, Richard E.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Bajwa, Rajinder S.] Nationwide Childrens Hosp, Columbus, OH USA. [Copelan, Edward A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Wirk, Baldeep] Shands Healthcare, Gainesville, FL USA. [Wirk, Baldeep] Univ Florida, Gainesville, FL USA. [Deeg, H. Joachim J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Battiwalla, Minoo] NHLBI, Bethesda, MD 20892 USA. [MacMillan, Margaret L.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horn, Biljana N.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Socie, Gerard] Hop St Louis, Paris, France. [Olsson, Richard] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Fasth, Anders L.] Univ Gothenburg, Gothenburg, Sweden. [Bonfim, Carmem M.; Pasquini, Ricardo] Univ Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, Brazil. [George, Biju] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Lewis, Victor A.] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada. [Slavin, Shimon] Int Ctr Cell Therapy & Canc Immunotherapy, Tel Aviv, Israel. [Stepensky, Polina] Hadassah Med Ctr, IL-91120 Jerusalem, Israel. [Bierings, Marc] Wihelmina Childrens Hosp, Utrecht, Netherlands. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, London, England. RP Ayas, M (reprint author), King Faisal Specialist Hosp & Res Ctr, POB 3354,MBC 53, Riyadh 11211, Saudi Arabia. EM mouhab@kfshrc.edu.sa RI Bajwa, Rajinder/E-2685-2011; OI Olsson, Richard/0000-0001-5970-2128; Fasth, Anders/0000-0002-0033-740X FU NCI NIH HHS [U24-CA76518]; NHLBI NIH HHS [5U01HL069294]; PHS HHS [HHSH234200637015C, N00014-06-1-0704, N00014-08-1-0058] NR 55 TC 21 Z9 21 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2013 VL 31 IS 13 BP 1669 EP + DI 10.1200/JCO.2012.45.9719 PG 10 WC Oncology SC Oncology GA 133PU UT WOS:000318152200015 PM 23547077 ER PT J AU Trevino, KM Fasciano, K Prigerson, HG AF Trevino, Kelly M. Fasciano, Karen Prigerson, Holly G. TI Patient-Oncologist Alliance, Psychosocial Well-Being, and Treatment Adherence Among Young Adults With Advanced Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; WORKING ALLIANCE; THERAPEUTIC ALLIANCE; BREAST-CANCER; COMPLICATED GRIEF; SOCIAL SUPPORT; META-ANALYSIS; ADOLESCENT; SCALE; CARE AB Purpose Patients who develop a strong alliance with their health care providers have been shown to have higher levels of psychosocial well-being and rates of treatment adherence. Young adults with cancer have lower levels of psychosocial well-being and treatment adherence relative to patients with cancer in other age groups. This study sought to evaluate the relationships between the patient-oncologist alliance, psychosocial well-being, and treatment adherence in young adults with advanced cancer. Patients and Methods Ninety-five young adults (age 20 to 40 years) with advanced cancer were administered measures of alliance, psychosocial well-being, willingness to adhere to treatment, and treatment adherence. Relationships between alliance and psychosocial well-being were examined bivariately. Multiple linear regression models examined the relationship between alliance and adherence, controlling for confounding influences (eg, psychosocial well-being). Results Alliance was significantly (P <= .01) and positively associated with greater perceived social support and less severe illness-related grief. After controlling for significant confounding influences (ie, metastases, appraised support, and grief), alliance remained significantly (P <= .01) associated with greater willingness to adhere to treatment and greater adherence to oral medication. Conclusion By developing a strong alliance, oncologists may enhance psychosocial well-being and increase treatment adherence in young adult patients with advanced cancer. J Clin Oncol 31:1683-1689. (C) 2013 by American Society of Clinical Oncology C1 [Trevino, Kelly M.; Fasciano, Karen; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 01225 USA. [Trevino, Kelly M.; Fasciano, Karen; Prigerson, Holly G.] Harvard Univ, Sch Med, Boston, MA USA. [Trevino, Kelly M.; Fasciano, Karen; Prigerson, Holly G.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, 1134 Dana Bldg,450 Brookline Ave, Boston, MA 01225 USA. EM holly_prigerson@dfci.harvard.edu FU NCI NIH HHS [R01 CA106370] NR 57 TC 21 Z9 21 U1 5 U2 21 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2013 VL 31 IS 13 BP 1683 EP 1689 DI 10.1200/JCO.2012.46.7993 PG 7 WC Oncology SC Oncology GA 133PU UT WOS:000318152200017 PM 23530105 ER PT J AU Neuberg, DS AF Neuberg, Donna S. TI No Evidence of Survival Benefit With Addition of Gemtuzumab Ozogamicin to Standard Medical Research Council Induction Chemotherapy Reply Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Neuberg, DS (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2013 VL 31 IS 13 BP 1701 EP 1701 DI 10.1200/JCO.2013.48.6589 PG 1 WC Oncology SC Oncology GA 133PU UT WOS:000318152200022 ER PT J AU Clark, CJ Morales-Oyarvide, V Zaydfudim, V Stauffer, J Deshpande, V Smyrk, TC Chari, ST Fernandez-del Castillo, C Farnell, MB AF Clark, Clancy J. Morales-Oyarvide, Vicente Zaydfudim, Victor Stauffer, John Deshpande, Vikram Smyrk, Thomas C. Chari, Suresh T. Fernandez-del Castillo, Carlos Farnell, Michael B. TI Short-Term and Long-Term Outcomes for Patients with Autoimmune Pancreatitis After Pancreatectomy: A Multi-institutional Study SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) / Meeting of the Pancreas-Club CY MAY 17-22, 2012 CL San Diego, CA SP Amer Assoc Study Liver Dis (AASLD), Amer Gastroenterol Assoc (AGA), Amer Soc Gastrointestinal Endoscopy (ASGE), Soc Surg Alimentary Tract (SSAT), Pancreas Club, Mayo Clin DE Autoimmune pancreatitis; IgG4; Surgery; Adult; Pancreatectomy; Chronic pancreatitis; Survival; Outcomes ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; INTERNATIONAL STUDY-GROUP; PANCREATICODUODENECTOMY; DISEASE; PROPOSAL; FISTULA; DEFINITION; MALIGNANCY; CONSENSUS; SURGERY AB Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis that may mimic adenocarcinoma of the pancreas. The aim of this study was to evaluate the short-term and long-term outcomes of pancreatectomy for patients with AIP. In this multi-institutional study, we identified all patients who underwent pancreatectomy for AIP from 1986 to 2011. AIP was confirmed by pathology review. Clinical presentation, operative details, and postoperative outcomes were analyzed. Seventy-four patients (median age, 60 years; 69 % male) with AIP underwent pancreatectomy. The main indication for operation was concern for malignancy (n = 59, 80 %). No patients were found to have pancreatic adenocarcinoma on final pathology. Major complications occurred in ten (14 %) patients, with one perioperative death (1 %). Clinically relevant (grade B/C) pancreatic fistulae occurred in two patients. No patients required reoperation for AIP and 11 (17 %) patients developed recurrent AIP. Although we do not advocate pancreatectomy for AIP, strong suspicion of malignancy may require an operation in selected patients. For patients with AIP, pancreatectomy resulted in few pancreatic fistulae, a low rate of re-intervention, and a 17 % recurrence rate. C1 [Clark, Clancy J.] Wake Forest Baptist Hlth, Dept Gen Surg, Winston Salem, NC 27157 USA. [Morales-Oyarvide, Vicente; Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastrointestinal Surg, Boston, MA USA. [Zaydfudim, Victor; Farnell, Michael B.] Mayo Clin, Div Gastroenterol & Gen Surg, Rochester, MN USA. [Stauffer, John] Mayo Clin, Div Gastroenterol & Gen Surg, Jacksonville, FL 32224 USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Smyrk, Thomas C.] Mayo Clin, Div Anat Pathol, Rochester, MN USA. [Chari, Suresh T.] Mayo Clin, Div Gastroenterol, Rochester, MN USA. RP Clark, CJ (reprint author), Wake Forest Baptist Hlth, Dept Gen Surg, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM cjclark@wakehealth.edu; vmorales2@partners.org; zayfudim.victor@mayo.edu; stauffer.john@mayo.edu; vdeshpande@partners.org; smyrk.thomas@mayo.edu; chari.suresh@mayo.edu; cfernandez@partners.orgA; farnell.michael@mayo.edu NR 30 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2013 VL 17 IS 5 BP 899 EP 906 DI 10.1007/s11605-013-2145-1 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 129SJ UT WOS:000317862200008 PM 23319396 ER PT J AU Hegde, JV Mulkern, RV Panych, LP Fennessy, FM Fedorov, A Maier, SE Tempany, CMC AF Hegde, John V. Mulkern, Robert V. Panych, Lawrence P. Fennessy, Fiona M. Fedorov, Andriy Maier, Stephan E. Tempany, Clare M. C. TI Multiparametric MRI of prostate cancer: An update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE prostate cancer; multiparametric MRI; T2-weighted imaging; diffusion-weighted imaging; dynamic contrast-enhanced imaging; magnetic resonance spectroscopy ID APPARENT DIFFUSION-COEFFICIENT; CONTRAST-ENHANCED MRI; MAGNETIC-RESONANCE-SPECTROSCOPY; LINE-SCAN DIFFUSION; IN-VIVO; ENDORECTAL-COIL; 3 T; PERIPHERAL ZONE; RADICAL PROSTATECTOMY; SURFACE COIL AB Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. J. Magn. Reson. Imaging 2013;37:10351054. (c) 2013 Wiley Periodicals, Inc. C1 [Hegde, John V.; Mulkern, Robert V.; Panych, Lawrence P.; Fennessy, Fiona M.; Fedorov, Andriy; Maier, Stephan E.; Tempany, Clare M. C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hegde, John V.] Harvard Univ, Sch Med, Boston, MA USA. [Mulkern, Robert V.] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Radiol, Boston, MA USA. [Fennessy, Fiona M.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Tempany, CMC (reprint author), Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, L1 050,75 Francis St, Boston, MA 02115 USA. EM ctempany@bwh.harvard.edu OI Fedorov, Andrey/0000-0003-4806-9413 FU National Institutes of Health (NIH) [R01CA109246, P41EB015898, P41RR019703, U01CA151261, R01CA111288, P01CA067165, R01CA160902]; Harvard Medical School FX Contract grant sponsor: National Institutes of Health (NIH); Contract grant numbers: R01CA109246, P41EB015898, P41RR019703, U01CA151261, R01CA111288, P01CA067165, and R01CA160902.; We thank Harvard Medical School for its research fellowship support to one of the authors (J.V.H.). We also thank Louise Greenberg, Aida Faria, and our technologists for their dedication to our patients and our clinical research program. NR 107 TC 65 Z9 67 U1 2 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2013 VL 37 IS 5 BP 1035 EP 1054 DI 10.1002/jmri.23860 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132DX UT WOS:000318049200003 PM 23606141 ER PT J AU Villano, JL Wen, PY Lee, EQ Nayak, L Reardon, DA Rosenfeld, MR AF Villano, J. Lee Wen, Patrick Y. Lee, Eudocia Q. Nayak, Lakshmi Reardon, David A. Rosenfeld, Myrna R. TI PCV for anaplastic oligodendrogliomas: back to the future or a step backwards? A point/counterpoint discussion SO JOURNAL OF NEURO-ONCOLOGY LA English DT Editorial Material ID PHASE-III TRIAL; VINCRISTINE; TUMORS; CHEMOTHERAPY; TEMOZOLOMIDE; PROCARBAZINE; LOMUSTINE; RADIOTHERAPY; SURVIVAL C1 [Villano, J. Lee] Univ Kentucky, Dept Internal Med, Lexington, KY USA. [Villano, J. Lee] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY USA. [Wen, Patrick Y.; Lee, Eudocia Q.; Nayak, Lakshmi; Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Wen, Patrick Y.; Lee, Eudocia Q.; Nayak, Lakshmi] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Wen, Patrick Y.; Lee, Eudocia Q.; Nayak, Lakshmi; Reardon, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Rosenfeld, Myrna R.] Hosp Clin Barcelona, IDIBAPS, Dept Neurol, E-08036 Barcelona, Spain. RP Rosenfeld, MR (reprint author), Hosp Clin Barcelona, IDIBAPS, Dept Neurol, Villarroel 170, E-08036 Barcelona, Spain. EM mrrosenf@clinic.ub.es NR 20 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2013 VL 113 IS 1 BP 143 EP 147 DI 10.1007/s11060-013-1100-z PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 135PL UT WOS:000318300700017 PM 23479035 ER PT J AU Yoo, AJ Leslie-Mazwi, TM Jovin, TG AF Yoo, Albert J. Leslie-Mazwi, Thabele M. Jovin, Tudor G. TI Future directions in IAT: better studies, better selection, better timing and better techniques SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; CEREBRAL-ARTERY OCCLUSION; DOOR-TO-BALLOON; ENDOVASCULAR THERAPY; INFARCT VOLUME; MULTICENTER ANALYSIS; EARLY RECANALIZATION; NONCONTRAST CT; BLOOD-FLOW; TIME C1 [Yoo, Albert J.; Leslie-Mazwi, Thabele M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Neuroradiol Endovasc Neurosurg, Boston, MA 02114 USA. [Jovin, Tudor G.] Univ Pittsburgh, Med Ctr, Stroke Inst, Pittsburgh, PA USA. [Jovin, Tudor G.] Univ Pittsburgh, Med Ctr, UPMC Ctr Neuroendovasc Therapy, Pittsburgh, PA USA. RP Yoo, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Neuroradiol Endovasc Neurosurg, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org NR 62 TC 10 Z9 10 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2013 VL 5 SU 1 BP 1 EP 6 DI 10.1136/neurintsurg-2013-010741 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 134JQ UT WOS:000318206900001 ER PT J AU Gonzalez, RG Copen, WA Schaefer, PW Lev, MH Pomerantz, SR Rapalino, O Chen, JW Hunter, GJ Romero, JM Buchbinder, BR Larvie, M Hirsch, JA Gupta, R AF Gonzalez, Ramon Gilberto Copen, William A. Schaefer, Pamela W. Lev, Michael H. Pomerantz, Stuart R. Rapalino, Otto Chen, John W. Hunter, George J. Romero, Javier M. Buchbinder, Bradley R. Larvie, Mykol Hirsch, Joshua Adam Gupta, Rajiv TI The Massachusetts General Hospital acute stroke imaging algorithm: an experience and evidence based approach SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID ACUTE ISCHEMIC-STROKE; DIFFUSION-WEIGHTED MR; SYMPTOMATIC INTRACEREBRAL HEMORRHAGE; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-ARTERY OCCLUSION; MAGNETIC-RESONANCE; INTRAARTERIAL THROMBOLYSIS; ENDOVASCULAR THERAPY; HYPERACUTE STROKE; INFARCT VOLUME AB The Massachusetts General Hospital Neuroradiology Division employed an experience and evidence based approach to develop a neuroimaging algorithm to best select patients with severe ischemic strokes caused by anterior circulation occlusions (ACOs) for intravenous tissue plasminogen activator and endovascular treatment. Methods found to be of value included the National Institutes of Health Stroke Scale (NIHSS), non-contrast CT, CT angiography (CTA) and diffusion MRI. Perfusion imaging by CT and MRI were found to be unnecessary for safe and effective triage of patients with severe ACOs. An algorithm was adopted that includes: non-contrast CT to identify hemorrhage and large hypodensity followed by CIA to identify the ACO; diffusion MRI to estimate the core infarct; and NIHSS in conjunction with diffusion data to estimate the clinical penumbra. C1 [Gonzalez, Ramon Gilberto; Copen, William A.; Schaefer, Pamela W.; Lev, Michael H.; Pomerantz, Stuart R.; Rapalino, Otto; Chen, John W.; Hunter, George J.; Romero, Javier M.; Buchbinder, Bradley R.; Larvie, Mykol; Hirsch, Joshua Adam; Gupta, Rajiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA. EM rggonzalez@partners.org FU GE Healthcare FX JMR is on the imaging committee of the DIAS trial for Lundbeck Pharmaceuticals. MHL has research support from GE Healthcare and is a consultant for Millenium Pharmaceuticals. NR 50 TC 22 Z9 22 U1 0 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2013 VL 5 SU 1 BP 7 EP 12 DI 10.1136/neurintsurg-2013-010715 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 134JQ UT WOS:000318206900002 PM 23493340 ER PT J AU Morais, LT Leslie-Mazwi, TM Lev, MH Albers, GW Yoo, AJ AF Morais, Livia T. Leslie-Mazwi, Thabele M. Lev, Michael H. Albers, Gregory W. Yoo, Albert J. TI Imaging-based selection for intra-arterial stroke therapies SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; CEREBRAL-ARTERY OCCLUSION; FINAL INFARCT VOLUME; TISSUE-PLASMINOGEN ACTIVATOR; ANGIOGRAPHIC SOURCE IMAGES; MEAN TRANSIT-TIME; ENDOVASCULAR TREATMENT; CT ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE C1 [Morais, Livia T.; Lev, Michael H.; Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Diagnost Neuroradiol, Boston, MA USA. [Leslie-Mazwi, Thabele M.; Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Neuroradiol, Boston, MA USA. [Albers, Gregory W.] Stanford Univ, Dept Neurol, Stanford Stroke Ctr, Stanford, CA 94305 USA. RP Yoo, AJ (reprint author), Massachusetts Gen Hosp, Div Diagnost & Intervent Neuroradiol, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org NR 82 TC 5 Z9 5 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2013 VL 5 SU 1 BP 13 EP 20 DI 10.1136/neurintsurg-2013-010733 PG 8 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 134JQ UT WOS:000318206900003 ER PT J AU Rost, NS Smith, EE Nogueira, RG Fitzpatrick, KM Yoo, AJ Hirsch, JA Schwamm, LH AF Rost, Natalia S. Smith, Eric E. Nogueira, Raul G. Fitzpatrick, Kaitlin M. Yoo, Albert J. Hirsch, Joshua A. Schwamm, Lee H. TI Implementation of a patient selection protocol for intra-arterial therapy increases treatment rates in patients with acute ischemic stroke SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID MERCI TRIAL; THROMBOLYSIS; CT; PREDICTION; EFFICACY; VOLUMES AB Background Strategies for patient selection for intraarterial therapy (IAT) in acute ischemic stroke (AIS) are highly variable. The degree of protocol adoption and treatment rates associated with implementation of a service-wide patient selection IAT protocol were assessed. Methods All patients with AIS prospectively recorded in our stroke database from January 2007 to June 2009 were reviewed. The IAT patient selection protocol was implemented in March 2008. Patients were defined as likely to benefit (LTB) from IAT if they had brain imaging completed within 6 h from last known well time, NIH Stroke Scale score >= 8, infarct volume <= 100 ml and evidence of proximal artery occlusion. Results Of 1348 subjects identified, 118(8.7%) met the criteria for LTB and 62 (52%) underwent IAT. There was a significant increase in rates of IAT among LTB patients after protocol implementation (61% vs 40%, p<0.02). In LTB patients, factors associated with IAT were stroke duration (OR 0.78, 95% CI 0.6 to 0.9 per hour), arrival within later calendar months during study period (OR 1.1, 95% CI 1.02 to 1.2 per month), intravenous tissue plasminogen activator (OR 0.6, 95% Cl 0.4 to 0.9) and age (OR 0.98, 95% CI 0.95 to 1.02 per year). After multivariable adjustment, only stroke duration (OR 0.65, 95% CI 0.5 to 0.8 per hour) remained an independent predictor of IAT. Conclusions Most patients with AIS did not meet our criteria for LTB and only 52% of those defined as LTB received IAT. Protocol adoption increased the use of IAT over time; however, further exploration of factors associated with the reasons for non-treatment and the impact of IAT on outcomes is necessary. C1 [Rost, Natalia S.; Fitzpatrick, Kaitlin M.; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Nogueira, Raul G.] Emory Univ, Dept Neurol & Radiol, Atlanta, GA 30322 USA. [Yoo, Albert J.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Penumbra Inc (core imaging laboratory); Intra-tech, a development stage stroke device company FX NSR, EES and KMF have nothing to disclose. RGN is a member of the Physician Advisory Board for Concentric Medical, ev3 Neurovascular, Coaxia, Rapid Medical, and Neurointervention. He is also the PI for the TREVO-2 Trial but does not receive any consulting fees. AJY has received research funding from Penumbra Inc (core imaging laboratory for the START trial). JAB has received consulting fees from Intra-tech, a development stage stroke device company. LHS serves as paid stroke systems consultant to the Massachusetts Department of Public Health and the Chair of the GWTG National Steering Committee (unpaid). NR 18 TC 3 Z9 3 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2013 VL 5 SU 1 BP 44 EP 47 DI 10.1136/neurintsurg-2011-010240 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 134JQ UT WOS:000318206900008 ER PT J AU Mehta, B Leslie-Mazwi, TM Chandra, RV Chaudhry, ZA Rabinov, JD Hirsch, JA Schwamm, LH Rost, NS Yoo, AJ AF Mehta, Brijesh Leslie-Mazwi, Thabele M. Chandra, Ronil V. Chaudhry, Zeshan A. Rabinov, James D. Hirsch, Joshua A. Schwamm, Lee H. Rost, Natalia S. Yoo, Albert J. TI Assessing variability in neurointerventional practice patterns for acute ischemic stroke SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID ENDOVASCULAR THERAPY; SCALE SCORE; INTRAARTERIAL; TRIAL; RECANALIZATION; VOLUMES; DISEASE; SAFETY AB Background Intra-arterial therapy (AT) is increasingly used to treat patients with acute stroke with large vessel occlusions. There are minimal data and guidelines for treatment indications and performance standards. We aimed to gain a better understanding of real-world practice patterns for IAT. Methods An internet-based survey was launched to address six specific areas of IAT: practice setting, operator background, operational protocols, quality/safety, decision-making and treatment strategies. The survey invitation was distributed to members of multiple neurointerventional societies. Results Responses from 140 neurointerventionalists worldwide were analyzed. The median annual volume of IAT cases per institution was 40, and the median neurointerventional group size was three staff members. Independent predictors of case volume were presence of comprehensive stroke services and telestroke capability. The median minimum National Institutes of Health Stroke Scale score for treatment consideration was 8, although 60% of respondents reported no minimum score cut-off. There was no strict time window from symptom onset to treatment among 41% of respondents for anterior circulation strokes and among 56% for posterior circulation strokes, instead basing treatment decisions on clinical and imaging findings. Despite the emphasis on imaging-based selection, there was pronounced variability in the criteria used. Only 27% used one imaging approach exclusively. IAT following full- or partial-dose intravenous tissue plasminogen activator was performed by 89%. Mechanical devices were the predominant first-line therapy, but specific device usage depended on practice location. Approximately half preferred conscious sedation during IAT. Conclusions This survey illustrates significant variation among neurointerventionalists in the real-world use of AT Our findings highlight the need for evidence-based practice guidelines. C1 [Mehta, Brijesh; Leslie-Mazwi, Thabele M.; Schwamm, Lee H.; Rost, Natalia S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Mehta, Brijesh; Leslie-Mazwi, Thabele M.; Chandra, Ronil V.; Chaudhry, Zeshan A.; Rabinov, James D.; Hirsch, Joshua A.; Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Intervent Neuroradiol, Boston, MA 02114 USA. [Chaudhry, Zeshan A.; Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Diagnost Neuroradiol, Boston, MA 02114 USA. RP Mehta, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM bmehta@partners.org OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS [K23NS064052] FX JAH is on the MERCI Registry Steering Committee but receives no financial compensation. NSR is supported by the NINDS (K23NS064052). NR 22 TC 18 Z9 18 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2013 VL 5 SU 1 BP 52 EP 57 DI 10.1136/neurintsurg-2012-010565 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 134JQ UT WOS:000318206900010 PM 23235960 ER PT J AU Albuquerque, FC Fiorella, D Hirsch, JA Prestigiacomo, C Tarr, RW AF Albuquerque, Felipe C. Fiorella, David Hirsch, Joshua A. Prestigiacomo, Charles Tarr, Robert W. TI The tribulations of stroke trials SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; ENDOVASCULAR TREATMENT; SOURCE IMAGES; REVASCULARIZATION; OCCLUSIONS; SELECTION; THERAPY; VOLUME; CT C1 [Albuquerque, Felipe C.] Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ 85013 USA. [Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. [Prestigiacomo, Charles] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. [Tarr, Robert W.] Univ Hosp Case Med Ctr, Dept Radiol, Cleveland, OH USA. RP Albuquerque, FC (reprint author), Barrow Neurol Inst, Div Neurol Surg, 2910 N 3rd Ave, Phoenix, AZ 85013 USA. EM felipe.albuquerque@bnaneuro.net NR 17 TC 15 Z9 15 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAY PY 2013 VL 5 IS 3 BP 181 EP 183 DI 10.1136/neurintsurg-2013-010731 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 134JP UT WOS:000318206800001 PM 23572243 ER PT J AU Hill, KS Adams, JM AF Hill, Karen S. Adams, Jeffrey M. TI Emerging Nurse Scientists An Interview With Jeffrey M. Adams, PhD, RN SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Boston, MA 02114 USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM www.jonaeditor@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2013 VL 43 IS 5 BP 247 EP 249 DI 10.1097/NNA.0b013e31828ef2b9 PG 3 WC Nursing SC Nursing GA 132MF UT WOS:000318071800003 ER PT J AU Adams, JM Nikolaev, N Erickson, JI Ditomassi, M Jones, DA AF Adams, Jeffrey M. Nikolaev, Nikolay Erickson, Jeanette Ives Ditomassi, Marianne Jones, Dorothy A. TI Identification of the Psychometric Properties of the Leadership Influence Over Professional Practice Environments Scale SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PSYCHOLOGICAL EMPOWERMENT; HOSPITAL CHARACTERISTICS; WORK ENVIRONMENTS; OUTCOMES; IMPACT; MORTALITY AB This study uses the qualitatively developed Adams InfluenceModel (c) (AIM) and concepts from the psychometrically validated Revised Professional Practice Environment scale to guide the development of the Leadership Influence Over Professional Practice Environments Scale. Nurse executives and others can use this scale individually or in conjunction with instruments targeting staff or patient perceptions of their influence as part of health services research, leadership development, and professional practice environment enhancement strategy. C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Boston, MA 02114 USA. [Adams, Jeffrey M.; Erickson, Jeanette Ives; Ditomassi, Marianne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nikolaev, Nikolay; Jones, Dorothy A.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. [Nikolaev, Nikolay] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Jones, Dorothy A.] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, Ctr Innovat Care Delivery, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM JADAMS9@partners.org FU Yvonne L. Munn Center for Nursing Research; Connell Nursing Research Scholars grant FX This research was supported in part by an Yvonne L. Munn Center for Nursing Research Postdoctoral Fellowship grant and a Connell Nursing Research Scholars grant. NR 41 TC 2 Z9 2 U1 0 U2 1 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 MAY PY 2013 VL 43 IS 5 BP 258 EP 265 DI 10.1097/NNA.0b013e31828eeb55 PG 8 WC Nursing SC Nursing GA 132MF UT WOS:000318071800005 PM 23615367 ER PT J AU Pierre, JF Heneghan, AF Feliciano, RP Shanmuganayagam, D Roenneburg, DA Krueger, CG Reed, JD Kudsk, KA AF Pierre, Joseph F. Heneghan, Aaron F. Feliciano, Rodrigo P. Shanmuganayagam, Dhanansayan Roenneburg, Drew A. Krueger, Christian G. Reed, Jess D. Kudsk, Kenneth A. TI Cranberry Proanthocyanidins Improve the Gut Mucous Layer Morphology and Function in Mice Receiving Elemental Enteral Nutrition SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE enteral nutrition; proanthocyanidins; goblet cells; mucin; cytokines ID RECURRENT ULCERATIVE-COLITIS; TOTAL PARENTERAL-NUTRITION; MUCOSAL IMMUNITY; LYMPHOID-TISSUE; HOST-DEFENSE; GRAPE SEEDS; MUC2 MUCIN; RATS; POLYPHENOLS; PROCYANIDINS AB Background: Lamina propria Th2 cytokines, interleukin (IL)-4 and IL-13, stimulate goblet cell (GC) proliferation and MUC2 production, which protect the intestinal mucosa. Elemental enteral nutrition (EEN) reduces tissue IL-4 and impairs barrier function. Proanthocyanidins (PACs) stimulate oral mucin levels. We hypothesized that adding PAC to EEN would maintain Th2-without stimulating Th1-cytokines and preserve luminal MUC2 vs EEN alone. Materials and Methods: Seventy mice were randomized to 5 diet groups-standard chow, intragastric EEN, or EEN with lowPAC, midPAC (50 mg), or highPAC (100 mg PAC/kg BW)-for 5 days, starting 2 days after gastric cannulation. Ileal tissue was analyzed for histomorphology and the cytokines IL-4, IL-13, IL-1 beta, IL-6, and TNF-alpha by enzyme-linked immunosorbent assay. MUC2 was measured in intestinal washes. Results: EEN lowered IL-13 (P < .05) compared with standard chow, whereas IL-4 was not significant (P < .07). LowPAC and midPAC increased IL-13 (P < .05), whereas highPAC increased both IL-4 and IL-13 (P < .05) compared with EEN. All EEN diets reduced (P < .05) crypt depth compared with the chow group. Compared with standard chow, GC numbers and luminal MUC2 were reduced with EEN (P < .05). These effects were attenuated (P < .05) with midPAC and highPAC. No changes were observed in tissue Th1 cytokines. Conclusions: Adding PACs to EEN reverses impaired intestinal barrier function following EEN by improving the gut mucous layer and function through increased GC size and number as well as levels of MUC2 and ileal IL-4 and IL-13. (JPEN J Parenter Enteral Nutr. 2013;37:401-409) C1 [Pierre, Joseph F.; Heneghan, Aaron F.; Roenneburg, Drew A.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Pierre, Joseph F.; Feliciano, Rodrigo P.; Shanmuganayagam, Dhanansayan; Krueger, Christian G.; Reed, Jess D.] Univ Wisconsin, Dept Anim Sci, Madison, WI 53792 USA. [Feliciano, Rodrigo P.] Univ Wisconsin, Dept Food Sci, Madison, WI 53792 USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Ctr Clin Sci, G5-341 600 Highland Ave, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu OI Feliciano, Rodrigo/0000-0002-8116-997X FU Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [I01BX001672]; National Institutes of Health (NIH) [R01 GM53439]; Reed Research Group; Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BD/73067/2010] FX The project described was supported by award number I01BX001672 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development. The research was also supported by a National Institutes of Health (NIH) grant (R01 GM53439) and by the Reed Research Group.; Rodrigo P. Feliciano is recipient of a BD fellowship (SFRH/BD/73067/2010) from Fundacao para a Ciencia e a Tecnologia, Portugal. We would like to thank Jennifer J. Meudt and Michael P. Shea for their technical assistance and Dr Martha Vestling for her assistance with mass spectrometry. NR 58 TC 13 Z9 13 U1 3 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAY PY 2013 VL 37 IS 3 BP 401 EP 409 DI 10.1177/0148607112463076 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 131IW UT WOS:000317987600015 PM 23064255 ER PT J AU Duncan, LE AF Duncan, Laramie E. TI Paying Attention to All Results, Positive and Negative SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; GENE-ENVIRONMENT INTERACTION; HUMAN-BEHAVIOR; LIFE STRESS; DEPRESSION; METAANALYSIS; 5-HTTLPR; HERITABILITY; MODERATION; MODEL C1 [Duncan, Laramie E.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Broad Inst Massachusetts Inst Technol & Halyard M, Cambridge, MA 02138 USA. RP Duncan, LE (reprint author), Ctr Human Genet Res, Simches Res Bldg,185 Cambridge St, Boston, MA 02144 USA. EM lduncan@hsph.harvard.edu FU NICHD NIH HHS [T32HD007289]; NIMH NIH HHS [T32MH017119] NR 28 TC 7 Z9 7 U1 1 U2 12 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 MAY PY 2013 VL 52 IS 5 BP 462 EP 465 DI 10.1016/j.jaac.2013.02.007 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 136WW UT WOS:000318395100004 PM 23622847 ER PT J AU Patel, IJ Davidson, JC Nikolic, B Salazar, GM Schwartzberg, MS Walker, TG Saad, WE AF Patel, Indravadan J. Davidson, Jon C. Nikolic, Boris Salazar, Gloria M. Schwartzberg, Marc S. Walker, T. Gregory Saad, Wael E. CA Stand Practice Comm CIRSE Endorsement TI Addendum of Newer Anticoagulants to the SIR Consensus Guideline SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID ASSOCIATION TASK-FORCE; AMERICAN-COLLEGE; UNSTABLE ANGINA; MANAGEMENT; REVASCULARIZATION; STRATEGIES; INHIBITORS; DISEASE; UPDATE C1 [Patel, Indravadan J.; Davidson, Jon C.] Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA. [Nikolic, Boris] Stratton Albany Med Ctr, Dept Radiol, Albany, NY USA. [Salazar, Gloria M.] Harvard Univ, Dept Imaging, Sch Med, Boston, MA USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Sect Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. [Schwartzberg, Marc S.] Radiol Associates Cent Florida, Leesburg, FL USA. Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. RP Davidson, JC (reprint author), Soc Intervent Radiol, 3975 Fair Ridge Dr,Ste 400,North, Fairfax, VA 22033 USA. EM jon.davidson@uhhospitals.org NR 13 TC 17 Z9 17 U1 0 U2 2 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 MAY PY 2013 VL 24 IS 5 BP 641 EP 645 DI 10.1016/j.jvir.2012.12.007 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 135CL UT WOS:000318263500004 PM 23622037 ER PT J AU Olejnik, J Alonso, J Schmidt, KM Yan, Z Wang, W Marzi, A Ebihara, H Yang, JH Patterson, JL Ryabchikova, E Muhlberger, E AF Olejnik, Judith Alonso, Jesus Schmidt, Kristina M. Yan, Zhen Wang, Wei Marzi, Andrea Ebihara, Hideki Yang, Jinghua Patterson, Jean L. Ryabchikova, Elena Muehlberger, Elke TI Ebola Virus Does Not Block Apoptotic Signaling Pathways SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; DEPENDENT PROTEIN-KINASE; NF-KAPPA-B; CELL-DEATH; HEMORRHAGIC-FEVER; DENDRITIC CELLS; IN-VITRO; LYMPHOCYTE APOPTOSIS; CYNOMOLGUS MACAQUES; INFECTED PATIENTS AB Since viruses rely on functional cellular machinery for efficient propagation, apoptosis is an important mechanism to fight viral infections. In this study, we sought to determine the mechanism of cell death caused by Ebola virus (EBOV) infection by assaying for multiple stages of apoptosis and hallmarks of necrosis. Our data indicate that EBOV does not induce apoptosis in infected cells but rather leads to a nonapoptotic form of cell death. Ultrastructural analysis confirmed necrotic cell death of EBOV-infected cells. To investigate if EBOV blocks the induction of apoptosis, infected cells were treated with different apoptosis-inducing agents. Surprisingly, EBOV-infected cells remained sensitive to apoptosis induced by external stimuli. Neither receptor- nor mitochondrion-mediated apoptosis signaling was inhibited in EBOV infection. Although double-stranded RNA (dsRNA)-induced activation of protein kinase R (PKR) was blocked in EBOV-infected cells, induction of apoptosis mediated by dsRNA was not suppressed. When EBOV-infected cells were treated with dsRNA-dependent caspase recruiter (dsCARE), an antiviral protein that selectively induces apoptosis in cells containing dsRNA, virus titers were strongly reduced. These data show that the inability of EBOV to block apoptotic pathways may open up new strategies toward the development of antiviral therapeutics. C1 [Olejnik, Judith; Schmidt, Kristina M.; Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Olejnik, Judith; Schmidt, Kristina M.; Muehlberger, Elke] Boston Univ, Natl Emerging Infect Dis Labs, Boston, MA 02118 USA. [Olejnik, Judith] Univ Marburg, Inst Virol, D-35032 Marburg, Germany. [Alonso, Jesus; Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA. [Yan, Zhen; Wang, Wei] Fourth Mil Med Univ, Sch Pharm, Dept Pharmacogen, State Key Lab Canc Biol, Xian 710032, Peoples R China. [Marzi, Andrea; Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA. [Yang, Jinghua] Boston Univ, VA Boston Healthcare Syst, Dept Surg, Boston, MA 02118 USA. [Ryabchikova, Elena] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Russia. RP Muhlberger, E (reprint author), Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. EM muehlber@bu.edu RI Ryabchikova, Elena /G-3089-2013 OI Muhlberger, Elke/0000-0003-3547-9376; Ryabchikova, Elena /0000-0003-4714-1524 FU NIH [U01-AI082954, CO6 RR12087]; Boston University; German Research Foundation [SFB 535]; Manchot Foundation; National Natural Science Foundation of China [NSFC 3092803, NSFC 81071369]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by NIH grants U01-AI082954 (to E.M.) and CO6 RR12087 (to J.L.P. and J.A.), start-up funds from Boston University (to E.M.), and funding from the German Research Foundation (grant SFB 535 to E.M.) and the Manchot Foundation (to J.O. and E.M). The production of dsCARE was supported by grants from the National Natural Science Foundation of China (grants NSFC 3092803 and NSFC 81071369 to J.Y. and Z.Y.). Funding was also provided by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 77 TC 10 Z9 10 U1 1 U2 23 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2013 VL 87 IS 10 BP 5384 EP 5396 DI 10.1128/JVI.01461-12 PG 13 WC Virology SC Virology GA 133QT UT WOS:000318155000007 PM 23468487 ER PT J AU Ackerman, ME Dugast, AS McAndrew, EG Tsoukas, S Licht, AF Irvine, DJ Alter, G AF Ackerman, Margaret E. Dugast, Anne-Sophie McAndrew, Elizabeth G. Tsoukas, Stephen Licht, Anna F. Irvine, Darrell J. Alter, Galit TI Enhanced Phagocytic Activity of HIV-Specific Antibodies Correlates with Natural Production of Immunoglobulins with Skewed Affinity for Fc gamma R2a and Fc gamma R2b SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; GAMMA-RIIA GENOTYPE; B-CELL RESPONSES; FC-RECEPTOR; RHESUS MACAQUES; HIV-1-INFECTED INDIVIDUALS; FCGR2A POLYMORPHISM; DENDRITIC CELLS; IGG; BINDING AB While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both quantitative differences in the capacity of antibodies to drive phagocytosis and qualitative differences in their Fc gamma R usage profile. We demonstrate that antibodies from controllers and untreated progressors exhibit increased phagocytic activity, altered Fc domain glycosylation, and skewed interactions with Fc gamma R2a and Fc gamma R2b in both bulk plasma and HIV-specific IgG. While increased phagocytic activity may directly influence immune activation via clearance of inflammatory immune complexes, it is also plausible that Fc receptor usage patterns may regulate the immune response by modulating downstream signals following phagocytosis-driving passive degradation of internalized virus, release of immune modulating cytokines and chemokines, or priming of a more effective adaptive immune response. C1 [Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Ackerman, Margaret E.; Dugast, Anne-Sophie; McAndrew, Elizabeth G.; Tsoukas, Stephen; Licht, Anna F.; Irvine, Darrell J.; Alter, Galit] MIT, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA. [Ackerman, Margaret E.; Dugast, Anne-Sophie; McAndrew, Elizabeth G.; Tsoukas, Stephen; Licht, Anna F.; Irvine, Darrell J.; Alter, Galit] Harvard Univ, Charlestown, MA USA. [Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Irvine, Darrell J.] MIT, Dept Mat Sci, Cambridge, MA 02139 USA. RP Ackerman, ME (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM margaret.e.ackerman@dartmouth.edu RI Dugast, AnneSophie/L-9541-2015 FU Collaboration for AIDS Vaccine Discovery: HIV Controllers: Implications for Vaccine Design [43307]; Susan and Philip T. Ragon Foundation; Harvard University Center for AIDS Research postdoctoral fellowship (HUCFAR NIH/NIAID fund) [2P30AI060354-07] FX These studies were supported by the Collaboration for AIDS Vaccine Discovery (43307): HIV Controllers: Implications for Vaccine Design and the Susan and Philip T. Ragon Foundation. M.E.A. was supported by a Harvard University Center for AIDS Research postdoctoral fellowship (HUCFAR NIH/NIAID fund 2P30AI060354-07). NR 60 TC 36 Z9 37 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2013 VL 87 IS 10 BP 5468 EP 5476 DI 10.1128/JVI.03403-12 PG 9 WC Virology SC Virology GA 133QT UT WOS:000318155000014 PM 23468489 ER PT J AU Piccinin, AM Muniz-Terrera, G Clouston, S Reynolds, CA Thorvaldsson, V Deary, IJ Deeg, DJH Johansson, B Mackinnon, A Spiro, A Starr, JM Skoog, I Hofer, SM AF Piccinin, Andrea M. Muniz-Terrera, Graciela Clouston, Sean Reynolds, Chandra A. Thorvaldsson, Valgeir Deary, Ian J. Deeg, Dorly J. H. Johansson, Boo Mackinnon, Andrew Spiro, Avron, III Starr, John M. Skoog, Ingmar Hofer, Scott M. TI Coordinated Analysis of Age, Sex, and Education Effects on Change in MMSE Scores SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Cognitive; Coordinated Analysis; Education; Longitudinal; Mental Status Exam; Meta-analysis; Mixed Model ID MINI-MENTAL-STATE; 6-YEAR FOLLOW-UP; COGNITIVE DECLINE; ALZHEIMERS-DISEASE; OLD-AGE; RESERVE HYPOTHESIS; PROCESSING SPEED; DEMENTIA; PEOPLE; HEALTH AB We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ. C1 [Piccinin, Andrea M.; Clouston, Sean; Hofer, Scott M.] Univ Victoria, Dept Psychol, Victoria, BC V8W 2Y2, Canada. [Muniz-Terrera, Graciela] MRC Unit Lifelong Hlth & Ageing, London, England. [Reynolds, Chandra A.] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. [Thorvaldsson, Valgeir; Johansson, Boo] Univ Gothenburg, Dept Psychol, Gothenburg, Sweden. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland. [Deeg, Dorly J. H.] VU Univ Med Ctr LASA, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Mackinnon, Andrew] Univ Melbourne, Ctr Youth Mental Hlth Res, Melbourne, Vic 3010, Australia. [Spiro, Avron, III] VA Boston Healthcare Syst, Normat Aging Study, Boston, MA USA. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland. [Skoog, Ingmar] Univ Gothenburg, Gothenburg, Sweden. RP Piccinin, AM (reprint author), Univ Victoria, Dept Psychol, Victoria, BC V8W 2Y2, Canada. RI Clouston, Sean/L-4653-2013; Hofer, Scott/D-9090-2014; OI Clouston, Sean/0000-0002-6124-0329; Hofer, Scott/0000-0001-8923-4337; Spiro III, Avron/0000-0003-4080-8621; Mackinnon, Andrew/0000-0003-0831-9801 FU National Institute on Aging at the National Institutes of Health [AG026453, AG08861]; National Institute on Aging [AG04563, AG10175]; MacArthur Foundation Research Network on Successful Aging; Swedish Council for Social Research [97:0147:1B]; Swedish Research Council [2007-2722]; Australian National Health and Medical Research Council; Swedish Council for Working Life and Social Research; Adlerbertska Foundation; Hjalmar Svensson Foundation; Knut and Alice Wallenberg Foundation; Wenner-Gren Foundations; Wilhelm and Martina Lundgrens Foundation; Swedish Research Council; Swedish Brain Power; Epilife; Canadian Institutes for Health Research [CUK-103284]; U.S. Department of Veterans Affairs FX This work was supported by the National Institute on Aging at the National Institutes of Health (grant number AG026453) in support of the Integrative Analysis of Longitudinal Studies of Aging (IALSA) research network. Swedish Adoption/Twin Study of Aging (SATSA) has been funded by the National Institute on Aging (AG04563, AG10175), the MacArthur Foundation Research Network on Successful Aging, the Swedish Council for Social Research (97:0147:1B), and the Swedish Research Council (2007-2722). Longitudinal Aging Study Amsterdam (LASA) is largely supported by the Netherlands Ministry of Health Welfare and Sports. Healthy Older Person Edinburgh (HOPE) was funded by the Chief Scientist Office, U.K. Canberra Longitudinal Study (CLS) was funded by the Australian National Health and Medical Research Council. Origins of Variance in the Oldest-Old (OCTO-Twin) data collection was funded by the National Institute on Aging at the National Institutes of Health (grant number AG08861), the Swedish Council for Working Life and Social Research, the Adlerbertska Foundation, the Hjalmar Svensson Foundation, the Knut and Alice Wallenberg Foundation, the Wenner-Gren Foundations, and the Wilhelm and Martina Lundgrens Foundation. Current work on Gerontological and Geriatric Population Studies in Gothenburg, Sweden (H70) and OCTO-Twin was supported by the Swedish Research Council, Swedish Council for Working Life and Social Research, Swedish Brain Power, and Epilife. H-70 was funded by the Swedish Research Council. Support was provided to S. Clouston by the Canadian Institutes for Health Research (CUK-103284) and to A. Spiro by Merit Review and Research Career Scientist Awards from the U.S. Department of Veterans Affairs. This article, however, does not represent the views of the U.S. Department of Veterans Affairs. NR 65 TC 21 Z9 24 U1 2 U2 27 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 2013 VL 68 IS 3 BP 374 EP 390 DI 10.1093/geronb/gbs077 PG 17 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 132PU UT WOS:000318081800007 PM 23033357 ER PT J AU Assis, L Moretti, AIS Abrahao, TB de Souza, HP Hamblin, MR Parizotto, NA AF Assis, Livia Soares Moretti, Ana Iochabel Abrahao, Thalita Balsamo de Souza, Heraldo Possolo Hamblin, Michael R. Parizotto, Nivaldo Antonio TI Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion SO LASERS IN MEDICAL SCIENCE LA English DT Article DE LLLT; Muscle cryolesion; Muscle regeneration; MRFs; Growth factors ID SATELLITE CELL-PROLIFERATION; SKELETAL-MUSCLE; IRRADIATION PROMOTES; MOLECULAR REGULATION; OXIDATIVE STRESS; GROWTH-FACTOR; IN-VITRO; ANGIOGENESIS; DIFFERENTIATION; EXPRESSION AB Muscle regeneration is a complex phenomenon, involving replacement of damaged fibers by new muscle fibers. During this process, there is a tendency to form scar tissue or fibrosis by deposition of collagen that could be detrimental to muscle function. New therapies that could regulate fibrosis and favor muscle regeneration would be important for physical therapy. Low-level laser therapy (LLLT) has been studied for clinical treatment of skeletal muscle injuries and disorders, even though the molecular and cellular mechanisms have not yet been clarified. The aim of this study was to evaluate the effects of LLLT on molecular markers involved in muscle fibrosis and regeneration after cryolesion of the tibialis anterior (TA) muscle in rats. Sixty Wistar rats were randomly divided into three groups: control, injured TA muscle without LLLT, injured TA muscle treated with LLLT. The injured region was irradiated daily for four consecutive days, starting immediately after the lesion using an AlGaAs laser (808 nm, 30 mW, 180 J/cm(2); 3.8 W/cm(2), 1.4 J). The animals were sacrificed on the fourth day after injury. LLLT significantly reduced the lesion percentage area in the injured muscle (p < 0.05), increased mRNA levels of the transcription factors MyoD and myogenin (p < 0.01) and the pro-angiogenic vascular endothelial growth factor (p < 0.01). Moreover, LLLT decreased the expression of the profibrotic transforming growth factor TGF-beta mRNA (p < 0.01) and reduced type I collagen deposition (p < 0.01). These results suggest that LLLT could be an effective therapeutic approach for promoting skeletal muscle regeneration while preventing tissue fibrosis after muscle injury. C1 [Assis, Livia; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos, Lab Electrothermophototherapy, Dept Physiotherapy, BR-13560 Sao Carlos, SP, Brazil. [Soares Moretti, Ana Iochabel; de Souza, Heraldo Possolo] Univ Sao Paulo, Fac Med, Emergency Med Div, Sao Paulo, Brazil. [Soares Moretti, Ana Iochabel] IAMSPE, Postgrad Hlth Sci Program, Sao Paulo, Brazil. [Abrahao, Thalita Balsamo] Univ Sao Paulo, Fac Med, Inst Heart, Lab Vasc Biol,Dept Cardiopneumol, Sao Paulo, Brazil. [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.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Moretti, AIS (reprint author), Univ Sao Paulo, Fac Med, Emergency Med Div, Av Dr Arnaldo,455 Sala 3189 01246-903, Sao Paulo, Brazil. EM aismoretti@yahoo.com.br RI PARIZOTTO, Nivaldo/D-5347-2014; Assis, Livia/H-8299-2012; OI PARIZOTTO, Nivaldo/0000-0003-1774-9053; Assis, Livia/0000-0002-8343-3375; Hamblin, Michael/0000-0001-6431-4605 FU CAPES; CNPQ; FAPESP; NIH [R01AI050875] FX We acknowledge CAPES, CNPQ and FAPESP for financial support. MR Hamblin was supported by NIH (grant R01AI050875). Emergency Medicine Division (LIM 51), Faculdade de Medicina da Universidade de Sao Paulo to provide technical support in biochemical and molecular biology analyses and NUPEN (Nucleo de Pesquisa e Ensino em Fototerapia nas Ciencias da Saude) for supporting and calibrating the laser equipment. NR 41 TC 25 Z9 28 U1 0 U2 19 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0268-8921 J9 LASER MED SCI JI Lasers Med. Sci. PD MAY PY 2013 VL 28 IS 3 BP 947 EP 955 DI 10.1007/s10103-012-1183-3 PG 9 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA 134BL UT WOS:000318184600032 PM 22898787 ER PT J AU Riedel, CG Dowen, RH Lourenco, GF Kirienko, NV Heimbucher, T West, JA Bowman, SK Kingston, RE Dillin, A Asara, JM Ruvkun, G AF Riedel, Christian G. Dowen, Robert H. Lourenco, Guinevere F. Kirienko, Natalia V. Heimbucher, Thomas West, Jason A. Bowman, Sarah K. Kingston, Robert E. Dillin, Andrew Asara, John M. Ruvkun, Gary TI DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity SO NATURE CELL BIOLOGY LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; C-ELEGANS; LIFE-SPAN; GENE-EXPRESSION; CELL-DIFFERENTIATION; HUMAN GENOME; CHIP-SEQ; RNA-SEQ; COMPLEX; MUTANTS AB Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation. C1 [Riedel, Christian G.; Dowen, Robert H.; Lourenco, Guinevere F.; Kirienko, Natalia V.; West, Jason A.; Bowman, Sarah K.; Kingston, Robert E.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Riedel, Christian G.; Dowen, Robert H.; Lourenco, Guinevere F.; Kirienko, Natalia V.; West, Jason A.; Bowman, Sarah K.; Kingston, Robert E.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Heimbucher, Thomas; Dillin, Andrew] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA. [Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Med, 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 RI West, Jason/I-4445-2014; OI West, Jason/0000-0002-7252-8651; Riedel, Christian/0000-0002-3689-8022 FU National Institutes of Health [AG014161, AG016636, 5P30CA006516, 2P01CA120964, F32GM093491, F32AI100501-01, GM048405]; Human Frontier Science Program; European Molecular Biology Organization; American Cancer Society [122240-PF-12-078-01-RMC]; Tosteson Postdoctoral Fellowship Award; Damon Runyon Cancer Research Foundation; Glenn Foundation for Medical Research; Austrian Science Fund (FWF) FX We thank H. Sawa (National Institute of Genetics, Japan), S. Mitani (Tokyo Women's Medical University, Japan), M. Hansen (Sanford-Burnham Medical Research Institute, USA) and the Caenorhabditis Genetics Center for strains. We thank G. Hayes, U. Kim, M. Borowski, A. Puczinska and D. Gran for experimental support. We thank I. Cheeseman, K. Bouazoune, M. Simon, B. Ardehali, W. Mair, T. Montgomery and the Avruch laboratory for helpful discussions. This work was supported by grants from the National Institutes of Health to G.R. (AG014161 and AG016636), J.M.A. (5P30CA006516 and 2P01CA120964), J.A.W. (F32GM093491), N.V.K. (F32AI100501-01) and R.E.K. (GM048405). C.G.R. was supported by long-term fellowships from the Human Frontier Science Program and the European Molecular Biology Organization, R.H.D. by the American Cancer Society (122240-PF-12-078-01-RMC), N.V.K. by a Tosteson Postdoctoral Fellowship Award, S.K.B. by the Damon Runyon Cancer Research Foundation, and T.H. by the Glenn Foundation for Medical Research and the Austrian Science Fund (FWF). NR 55 TC 54 Z9 54 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2013 VL 15 IS 5 BP 491 EP + DI 10.1038/ncb2720 PG 21 WC Cell Biology SC Cell Biology GA 135DD UT WOS:000318265300008 PM 23604319 ER PT J AU Nombela-Arrieta, C Pivarnik, G Winkel, B Canty, KJ Harley, B Mahoney, JE Park, SY Lu, JY Protopopov, A Silberstein, LE AF Nombela-Arrieta, Cesar Pivarnik, Gregory Winkel, Beatrice Canty, Kimberly J. Harley, Brendan Mahoney, John E. Park, Shin-Young Lu, Jiayun Protopopov, Alexei Silberstein, Leslie E. TI Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment SO NATURE CELL BIOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; VASCULAR NICHE; SELF-RENEWAL; OXYGEN; DIFFERENTIATION; HIF-1-ALPHA; IDENTIFICATION; BALANCE; BIOLOGY; RESIDE AB The existence of a haematopoietic stem cell niche as a spatially confined regulatory entity relies on the notion that haematopoietic stem and progenitor cells (HSPCs) are strategically positioned in unique bone marrow microenvironments with defined anatomical and functional features. Here, we employ a powerful imaging cytometry platform to perform a comprehensive quantitative analysis of HSPC distribution in bone marrow cavities of femoral bones. We find that HSPCs preferentially localize in endosteal zones, where most closely interact with sinusoidal and non-sinusoidal bone marrow microvessels, which form a distinctive circulatory system. In situ tissue analysis reveals that HSPCs exhibit a hypoxic profile, defined by strong retention of pimonidazole and expression of HIF-1 alpha, regardless of localization throughout the bone marrow, adjacency to vascular structures or cell-cycle status. These studies argue that the characteristic hypoxic state of HSPCs is not solely the result of a minimally oxygenated niche but may be partially regulated by cell-specific mechanisms. C1 [Nombela-Arrieta, Cesar; Pivarnik, Gregory; Winkel, Beatrice; Canty, Kimberly J.; Park, Shin-Young; Lu, Jiayun; Silberstein, Leslie E.] Childrens Hosp Boston, Dept Lab Med, Div Transfus Med, Boston, MA 02115 USA. [Harley, Brendan] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Mahoney, John E.; Protopopov, Alexei] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Nombela-Arrieta, C (reprint author), Childrens Hosp Boston, Dept Lab Med, Div Transfus Med, 300 Longwood Ave, Boston, MA 02115 USA. EM Cesar.NombelaArrieta@childrens.harvad.edu; leslie.silberstein@childrens.harvard.edu OI Nombela-Arrieta, Cesar/0000-0003-0415-259X; Harley, Brendan/0000-0001-5458-154X FU Human Frontiers in Science Program long-term fellowship [00194/2008-L]; Harvard Stem Cell Institute; National Heart Lung and Blood Institute, USA [P01 HL095489, R01 HL093139, HHSN268201000009C] FX We are grateful to D. Rossi, L. Purton and C. P. Lin for critical reading of the manuscript and thank the Compucyte Corporation team for helpful advice. C.N-A. was a recipient of Human Frontiers in Science Program long-term fellowship 00194/2008-L. This work was financially supported in part by a seed grant from the Harvard Stem Cell Institute. L.E.S. is supported by grants P01 HL095489 and R01 HL093139, and contract HHSN268201000009C from the National Heart Lung and Blood Institute, USA. NR 41 TC 150 Z9 150 U1 3 U2 25 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 MAY PY 2013 VL 15 IS 5 BP 533 EP + DI 10.1038/ncb2730 PG 20 WC Cell Biology SC Cell Biology GA 135DD UT WOS:000318265300013 PM 23624405 ER PT J AU Engelhart, AE Powner, MW Szostak, JW AF Engelhart, Aaron E. Powner, Matthew W. Szostak, Jack W. TI Functional RNAs exhibit tolerance for non-heritable 2 '-5 ' versus 3 '-5 ' backbone heterogeneity SO NATURE CHEMISTRY LA English DT Article ID GLYCEROL NUCLEIC-ACID; HAMMERHEAD RIBOZYME; GENETIC SYSTEM; TEMPLATE; LIFE; OLIGOMERIZATION; EVOLUTION; ANALOGS; ORIGIN; OLIGORIBONUCLEOTIDES AB A plausible process for non-enzymatic RNA replication would greatly simplify models of the transition from prebiotic chemistry to simple biology. However, all known conditions for the chemical copying of an RNA template result in the synthesis of a complementary strand that contains a mixture of 2'-5' and 3'-5' linkages, rather than the selective synthesis of only 3'-5' linkages as found in contemporary RNA. Here we show that such backbone heterogeneity is compatible with RNA folding into defined three-dimensional structures that retain molecular recognition and catalytic properties and, therefore, would not prevent the evolution of functional RNAs such as ribozymes. Moreover, the same backbone heterogeneity lowers the melting temperature of RNA duplexes that would otherwise be too stable for thermal strand separation. By allowing copied strands to dissociate, this heterogeneity may have been one of the essential features that allowed RNA to emerge as the first biopolymer. C1 [Engelhart, Aaron E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Engelhart, AE (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Engelhart, Aaron/0000-0002-1849-7700; Powner, Matthew/0000-0002-6368-3190 FU NSF [CHE-0809413]; NASA FX J.W.S. is an Investigator of the Howard Hughes Medical Institute (HHMI). A. E. E. is supported by an appointment to the NASA Postdoctoral Program, administered by Oak Ridge Associated Universities through a contract with NASA. M. W. P. was an HHMI Research Associate. This work was supported in part through NSF Grant CHE-0809413 to J.W.S. We thank J. Craig Blain for oligonucleotide mass spectrometry, K. Adamala for advice with RNA melting experiments and N. Prywes for helpful discussions and assistance with figure preparation. NR 44 TC 37 Z9 40 U1 5 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1755-4330 EI 1755-4349 J9 NAT CHEM JI Nat. Chem. PD MAY PY 2013 VL 5 IS 5 BP 390 EP 394 DI 10.1038/nchem.1623 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 131AE UT WOS:000317961700012 PM 23609089 ER PT J AU Dulak, AM Stojanov, P Peng, SY Lawrence, MS Fox, C Stewart, C Bandla, S Imamura, Y Schumacher, SE Shefler, E McKenna, A Carter, SL Cibulskis, K Sivachenko, A Saksena, G Voet, D Ramos, AH Auclair, D Thompson, K Sougnez, C Onofrio, RC Guiducci, C Beroukhim, R Zhou, ZR Lin, L Lin, J Reddy, R Chang, A Landrenau, R Pennathur, A Ogino, S Luketich, JD Golub, TR Gabriel, SB Lander, ES Beer, DG Godfrey, TE Getz, G Bass, AJ AF Dulak, Austin M. Stojanov, Petar Peng, Shouyong Lawrence, Michael S. Fox, Cameron Stewart, Chip Bandla, Santhoshi Imamura, Yu Schumacher, Steven E. Shefler, Erica McKenna, Aaron Carter, Scott L. Cibulskis, Kristian Sivachenko, Andrey Saksena, Gordon Voet, Douglas Ramos, Alex H. Auclair, Daniel Thompson, Kristin Sougnez, Carrie Onofrio, Robert C. Guiducci, Candace Beroukhim, Rameen Zhou, Zhongren Lin, Lin Lin, Jules Reddy, Rishindra Chang, Andrew Landrenau, Rodney Pennathur, Arjun Ogino, Shuji Luketich, James D. Golub, Todd R. Gabriel, Stacey B. Lander, Eric S. Beer, David G. Godfrey, Tony E. Getz, Gad Bass, Adam J. TI Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity SO NATURE GENETICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ERBB2 KINASE DOMAIN; SOMATIC MUTATIONS; GENE-MUTATIONS; BARRETT-ESOPHAGUS; STRUCTURAL BASIS; PROSTATE-CANCER; TROYER-SYNDROME; RAC ACTIVATION; LUNG-CANCER AB The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a 5-year survival rate of similar to 15%, the identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole-exome sequencing of 149 EAC tumor-normal pairs, 15 of which have also been subjected to whole-genome sequencing. We identify a mutational signature defined by a high prevalence of A>C transversions at AA dinucleotides. Statistical analysis of exome data identified 26 significantly mutated genes. Of these genes, five (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) have previously been implicated in EAC. The new significantly mutated genes include chromatin-modifying factors and candidate contributors SPG20, TLR4, ELMO1 and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 identifies increased cellular invasion. Therefore, we suggest the potential activation of the RAC1 pathway as a contributor to EAC tumorigenesis. C1 [Dulak, Austin M.; Stojanov, Petar; Peng, Shouyong; Fox, Cameron; Imamura, Yu; Schumacher, Steven E.; Beroukhim, Rameen; Ogino, Shuji; Golub, Todd R.; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dulak, Austin M.; Stojanov, Petar; Peng, Shouyong; Lawrence, Michael S.; Stewart, Chip; Schumacher, Steven E.; Shefler, Erica; McKenna, Aaron; Carter, Scott L.; Cibulskis, Kristian; Sivachenko, Andrey; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Auclair, Daniel; Thompson, Kristin; Sougnez, Carrie; Onofrio, Robert C.; Guiducci, Candace; Beroukhim, Rameen; Golub, Todd R.; Gabriel, Stacey B.; Lander, Eric S.; Getz, Gad; Bass, Adam J.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Dulak, Austin M.; Stojanov, Petar; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA USA. [Bandla, Santhoshi; Zhou, Zhongren; Godfrey, Tony E.] Univ Rochester, Dept Surg, Rochester, NY USA. [Beroukhim, Rameen; Bass, Adam J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen; Ogino, Shuji; Golub, Todd R.; Lander, Eric S.; Bass, Adam J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lin, Lin; Lin, Jules; Reddy, Rishindra; Chang, Andrew; Beer, David G.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Landrenau, Rodney; Pennathur, Arjun; Luketich, James D.] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Getz, Gad] Dept Pathol, Boston, MA USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM gadgetz@broadinstitute.org; adam_bass@dfci.harvard.edu RI Schumacher, Steven/E-9821-2013; Godfrey, Tony/A-5572-2013; OI Schumacher, Steven/0000-0002-6819-5647; Godfrey, Tony/0000-0002-3283-6983; Chang, Andrew/0000-0001-9506-0425 FU US National Human Genome Research Institute (NHGRI) Large-Scale Sequencing Program [U54 HG003067]; National Cancer Institute [K08 CA134931, R01 CA151993]; DeGregorio Family Foundation; Karin Grunebaum Cancer Research Foundation; Target Cancer; Connecticut Conquers Cancer; Dana-Farber/Harvard Cancer Center GI Cancer Specialized Programs of Research Excellence (US National Institutes of Health (NIH)) [P50 CA127003]; NIH [CA163059, CA46592, CA090665, CA130853] FX We thank M. Meyerson for helpful discussions and review of the manuscript and members of the Broad Institute Biological Samples Platform, Genetic Analysis Platform and Genome Sequencing Platform for their assistance. We are also grateful for the physicians and hospital staff whose efforts in collecting these samples are essential to this research. This work was supported by the US National Human Genome Research Institute (NHGRI) Large-Scale Sequencing Program (U54 HG003067 to the Broad Institute, E. S. L.), the National Cancer Institute (K08 CA134931 to A.J.B.), the DeGregorio Family Foundation (A.J.B.), the Karin Grunebaum Cancer Research Foundation (A.J.B.), the Target Cancer (A.J.B.) and Connecticut Conquers Cancer (A.J.B.). S.O. and Y.I. are supported by the National Cancer Institute (R01 CA151993 to S.O.) and the Dana-Farber/Harvard Cancer Center GI Cancer Specialized Programs of Research Excellence (US National Institutes of Health (NIH) grant P50 CA127003). D. G. B. is supported by NIH grants CA163059 and CA46592. J.D.L. is supported by NIH grant CA090665. T. E. G. is supported by NIH grant CA130853. NR 81 TC 224 Z9 230 U1 7 U2 56 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAY PY 2013 VL 45 IS 5 BP 478 EP U37 DI 10.1038/ng.2591 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 133RU UT WOS:000318158200008 PM 23525077 ER PT J AU Berndt, SI Gustafsson, S Magi, R Ganna, A Wheeler, E Feitosa, MF Justice, AE Monda, KL Croteau-Chonka, DC Day, FR Esko, T Fall, T Ferreira, T Gentilini, D Jackson, AU Luan, JA Randall, JC Vedantam, S Willer, CJ Winkler, TW Wood, AR Workalemahu, T Hu, YJ Lee, SH Liang, LM Lin, DY Min, JL Neale, BM Thorleifsson, G Yang, J Albrecht, E Amin, N Bragg-Gresham, JL Cadby, G den Heijer, M Eklund, N Fischer, K Goel, A Hottenga, JJ Huffman, JE Jarick, I Johansson, A Johnson, T Kanoni, S Kleber, ME Konig, IR Kristiansson, K Kutalik, Z Lamina, C Lecoeur, C Li, G Mangino, M McArdle, WL Medina-Gomez, C Muller-Nurasyid, M Ngwa, JS Nolte, IM Lavinia, P Pechlivanis, S Perola, M Peters, MJ Preuss, M Rose, LM Shi, JX Shungin, D Smith, AV Strawbridge, RJ Surakka, I Teumer, A Trip, MD Tyrer, J Van Vliet-Ostaptchouk, JV Vandenput, L Waite, LL Zhao, JH Absher, D Asselbergs, FW Atalay, M Attwood, AP Balmforth, AJ Basart, H Beilby, J Bonnycastle, LL Brambilla, P Bruinenberg, M Campbell, H Chasman, DI Chines, PS Collins, FS Connell, JM Cookson, WO de Faire, U de Vegt, F Dei, M Dimitriou, M Edkins, S Estrada, K Evans, DM Farrall, M Ferrario, MM Ferrieres, J Franke, L Frau, F Gejman, PV Grallert, H Gronberg, H Gudnason, V Hall, AS Hall, P Hartikainen, AL Hayward, C Heard-Costa, NL Heath, AC Hebebrand, J Homuth, G Hu, FB Hunt, SE Hypponen, E Iribarren, C Jacobs, KB Jansson, JO Jula, A Kahonen, M Kathiresan, S Kee, F Khaw, KT Kivimaki, M Koenig, W Kraja, AT Kumari, M Kuulasmaa, K Kuusisto, J Laitinen, JH Lakka, TA Langenberg, C Launer, LJ Lind, L Lindstrom, J Liu, JJ Liuzzi, A Lokki, ML Lorentzon, M Madden, PA Magnusson, PK Manunta, P Marek, D Marz, W Leach, IM McKnight, B Medland, SE Mihailov, E Milani, L Montgomery, GW Mooser, V Muhleisen, TW Munroe, PB Musk, AW Narisu, N Navis, G Nicholson, G Nohr, EA Ong, KK Oostra, BA Palmer, CNA Palotie, A Peden, JF Pedersen, N Peters, A Polasek, O Pouta, A Pramstaller, PP Prokopenko, I Putter, C Radhakrishnan, A Raitakari, O Rendon, A Rivadeneira, F Rudan, I Saaristo, TE Sambrook, JG Sanders, AR Sanna, S Saramies, J Schipf, S Schreiber, S Schunkert, H Shin, SY Signorini, S Sinisalo, J Skrobek, B Soranzo, N Stancakova, A Stark, K Stephens, JC Stirrups, K Stolk, RP Stumvoll, M Swift, AJ Theodoraki, EV Thorand, B Tregouet, DA Tremoli, E Van der Klauw, MM van Meurs, JBJ Vermeulen, SH Viikari, J Virtamo, J Vitart, V Waeber, G Wang, ZM Widen, E Wild, SH Willemsen, G Winkelmann, BR Witteman, JCM Wolffenbuttel, BHR Wong, A Wright, AF Zillikens, MC Amouyel, P Boehm, BO Boerwinkle, E Boomsma, DI Caulfield, MJ Chanock, SJ Cupples, LA Cusi, D Dedoussis, GV Erdmann, J Eriksson, JG Franks, PW Froguel, P Gieger, C Gyllensten, U Hamsten, A Harris, TB Hengstenberg, C Hicks, AA Hingorani, A Hinney, A Hofman, A Hovingh, KG Hveem, K Illig, T Jarvelin, MR Jockel, KH Keinanen-Kiukaanniemi, SM Kiemeney, LA Kuh, D Laakso, M Lehtimaki, T Levinson, DF Martin, NG Metspalu, A Morris, AD Nieminen, MS Njolstad, I Ohlsson, C Oldehinkel, AJ Ouwehand, WH Palmer, LJ Penninx, B Power, C Province, MA Psaty, BM Qi, L Rauramaa, R Ridker, PM Ripatti, S Salomaa, V Samani, NJ Snieder, H Sorensen, TIA Spector, TD Stefansson, K Tonjes, A Tuomilehto, J Uitterlinden, AG Uusitupa, M van der Harst, P Vollenweider, P Wallaschofski, H Wareham, NJ Watkins, H Wichmann, HE Wilson, JF Abecasis, GR Assimes, TL Barroso, I Boehnke, M Borecki, IB Deloukas, P Fox, CS Frayling, T Groop, LC Haritunian, T Heid, IM Hunter, D Kaplan, RC Karpe, F Moffatt, MF Mohlke, KL O'Connell, JR Pawitan, Y Schadt, EE Schlessinger, D Steinthorsdottir, V Strachan, DP Thorsteinsdottir, U van Duijn, CM Visscher, PM Di Blasio, AM Hirschhorn, JN Lindgren, CM Morris, AP Meyre, D Scherag, A McCarthy, MI Speliotes, EK North, KE Loos, RJF Ingelsson, E AF Berndt, Sonja I. Gustafsson, Stefan Maegi, Reedik Ganna, Andrea Wheeler, Eleanor Feitosa, Mary F. Justice, Anne E. Monda, Keri L. Croteau-Chonka, Damien C. Day, Felix R. Esko, Tonu Fall, Tove Ferreira, Teresa Gentilini, Davide Jackson, Anne U. Luan, Jian'an Randall, Joshua C. Vedantam, Sailaja Willer, Cristen J. Winkler, Thomas W. Wood, Andrew R. Workalemahu, Tsegaselassie Hu, Yi-Juan Lee, Sang Hong Liang, Liming Lin, Dan-Yu Min, Josine L. Neale, Benjamin M. Thorleifsson, Gudmar Yang, Jian Albrecht, Eva Amin, Najaf Bragg-Gresham, Jennifer L. Cadby, Gemma den Heijer, Martin Eklund, Niina Fischer, Krista Goel, Anuj Hottenga, Jouke-Jan Huffman, Jennifer E. Jarick, Ivonne Johansson, Asa Johnson, Toby Kanoni, Stavroula Kleber, Marcus E. Koenig, Inke R. Kristiansson, Kati Kutalik, Zoltn Lamina, Claudia Lecoeur, Cecile Li, Guo Mangino, Massimo McArdle, Wendy L. Medina-Gomez, Carolina Mueller-Nurasyid, Martina Ngwa, Julius S. Nolte, Ilja M. Paternoster, Lavinia Pechlivanis, Sonali Perola, Markus Peters, Marjolein J. Preuss, Michael Rose, Lynda M. Shi, Jianxin Shungin, Dmitry Smith, Albert Vernon Strawbridge, Rona J. Surakka, Ida Teumer, Alexander Trip, Mieke D. Tyrer, Jonathan Van Vliet-Ostaptchouk, Jana V. Vandenput, Liesbeth Waite, Lindsay L. Zhao, Jing Hua Absher, Devin Asselbergs, Folkert W. Atalay, Mustafa Attwood, Antony P. Balmforth, Anthony J. Basart, Hanneke Beilby, John Bonnycastle, Lori L. Brambilla, Paolo Bruinenberg, Marcel Campbell, Harry Chasman, Daniel I. Chines, Peter S. Collins, Francis S. Connell, John M. Cookson, William O. de Faire, Ulf de Vegt, Femmie Dei, Mariano Dimitriou, Maria Edkins, Sarah Estrada, Karol Evans, David M. Farrall, Martin Ferrario, Marco M. Ferrieres, Jean Franke, Lude Frau, Francesca Gejman, Pablo V. Grallert, Harald Groenberg, Henrik Gudnason, Vilmundur Hall, Alistair S. Hall, Per Hartikainen, Anna-Liisa Hayward, Caroline Heard-Costa, Nancy L. Heath, Andrew C. Hebebrand, Johannes Homuth, Georg Hu, Frank B. Hunt, Sarah E. Hyppoenen, Elina Iribarren, Carlos Jacobs, Kevin B. Jansson, John-Olov Jula, Antti Kahonen, Mika Kathiresan, Sekar Kee, Frank Khaw, Kay-Tee Kivimaki, Mika Koenig, Wolfgang Kraja, Aldi T. Kumari, Meena Kuulasmaa, Kari Kuusisto, Johanna Laitinen, Jaana H. Lakka, Timo A. Langenberg, Claudia Launer, Lenore J. Lind, Lars Lindstrom, Jaana Liu, Jianjun Liuzzi, Antonio Lokki, Marja-Liisa Lorentzon, Mattias Madden, Pamela A. Magnusson, Patrik K. Manunta, Paolo Marek, Diana Maerz, Winfried Leach, Irene Mateo McKnight, Barbara Medland, Sarah E. Mihailov, Evelin Milani, Lili Montgomery, Grant W. Mooser, Vincent Muehleisen, Thomas W. Munroe, Patricia B. Musk, Arthur W. Narisu, Narisu Navis, Gerjan Nicholson, George Nohr, Ellen A. Ong, Ken K. Oostra, Ben A. Palmer, Colin N. A. Palotie, Aarno Peden, John F. Pedersen, Nancy Peters, Annette Polasek, Ozren Pouta, Anneli Pramstaller, Peter P. Prokopenko, Inga Puetter, Carolin Radhakrishnan, Aparna Raitakari, Olli Rendon, Augusto Rivadeneira, Fernando Rudan, Igor Saaristo, Timo E. Sambrook, Jennifer G. Sanders, Alan R. Sanna, Serena Saramies, Jouko Schipf, Sabine Schreiber, Stefan Schunkert, Heribert Shin, So-Youn Signorini, Stefano Sinisalo, Juha Skrobek, Boris Soranzo, Nicole Stancakova, Alena Stark, Klaus Stephens, Jonathan C. Stirrups, Kathleen Stolk, Ronald P. Stumvoll, Michael Swift, Amy J. Theodoraki, Eirini V. Thorand, Barbara Tregouet, David-Alexandre Tremoli, Elena Van der Klauw, Melanie M. van Meurs, Joyce B. J. Vermeulen, Sita H. Viikari, Jorma Virtamo, Jarmo Vitart, Veronique Waeber, Gerard Wang, Zhaoming Widen, Elisabeth Wild, Sarah H. Willemsen, Gonneke Winkelmann, Bernhard R. Witteman, Jacqueline C. M. Wolffenbuttel, Bruce H. R. Wong, Andrew Wright, Alan F. Zillikens, M. Carola Amouyel, Philippe Boehm, Bernhard O. Boerwinkle, Eric Boomsma, Dorret I. Caulfield, Mark J. Chanock, Stephen J. Cupples, L. Adrienne Cusi, Daniele Dedoussis, George V. Erdmann, Jeanette Eriksson, Johan G. Franks, Paul W. Froguel, Philippe Gieger, Christian Gyllensten, Ulf Hamsten, Anders Harris, Tamara B. Hengstenberg, Christian Hicks, Andrew A. Hingorani, Aroon Hinney, Anke Hofman, Albert Hovingh, Kees G. Hveem, Kristian Illig, Thomas Jarvelin, Marjo-Riitta Joeckel, Karl-Heinz Keinanen-Kiukaanniemi, Sirkka M. Kiemeney, Lambertus A. Kuh, Diana Laakso, Markku Lehtimaki, Terho Levinson, Douglas F. Martin, Nicholas G. Metspalu, Andres Morris, Andrew D. Nieminen, Markku S. Njolstad, Inger Ohlsson, Claes Oldehinkel, Albertine J. Ouwehand, Willem H. Palmer, Lyle J. Penninx, Brenda Power, Chris Province, Michael A. Psaty, Bruce M. Qi, Lu Rauramaa, Rainer Ridker, Paul M. Ripatti, Samuli Salomaa, Veikko Samani, Nilesh J. Snieder, Harold Sorensen, Thorkild I. A. Spector, Timothy D. Stefansson, Kari Tonjes, Anke Tuomilehto, Jaakko Uitterlinden, Andre G. Uusitupa, Matti van der Harst, Pim Vollenweider, Peter Wallaschofski, Henri Wareham, Nicholas J. Watkins, Hugh Wichmann, H-Erich Wilson, James F. Abecasis, Goncalo R. Assimes, Themistocles L. Barroso, Ines Boehnke, Michael Borecki, Ingrid B. Deloukas, Panos Fox, Caroline S. Frayling, Timothy Groop, Leif C. Haritunian, Talin Heid, Iris M. Hunter, David Kaplan, Robert C. Karpe, Fredrik Moffatt, Miriam F. Mohlke, Karen L. O'Connell, Jeffrey R. Pawitan, Yudi Schadt, Eric E. Schlessinger, David Steinthorsdottir, Valgerdur Strachan, David P. Thorsteinsdottir, Unnur van Duijn, Cornelia M. Visscher, Peter M. Di Blasio, Anna Maria Hirschhorn, Joel N. Lindgren, Cecilia M. Morris, Andrew P. Meyre, David Scherag, Andr McCarthy, Mark I. Speliotes, Elizabeth K. North, Kari E. Loos, Ruth J. F. Ingelsson, Erik TI Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture SO NATURE GENETICS LA English DT Article ID BODY-MASS INDEX; EXTREME OBESITY; MISSING HERITABILITY; COMMON VARIANTS; CONFER RISK; EARLY-ONSET; ASSOCIATION; POPULATION; EXPRESSION; SORTILIN AB Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. 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[Stark, Klaus; Hengstenberg, Christian] Univ Klinikum Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany. [Stumvoll, Michael; Tonjes, Anke] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Stumvoll, Michael; Tonjes, Anke] Univ Leipzig, Integrierte Forsch & Behandlungszentren IFB Adipo, D-04109 Leipzig, Germany. [Tregouet, David-Alexandre] Univ Paris 06, INSERM, UMRS 937, Inst Cardiometab & Nutr ICAN, Paris, France. [Tremoli, Elena] Univ Milan, Dipartimento Sci Farmacol & Biomol, Ctr Cardiol Monzino, Ist Ricovero & Cura Carattere Sci IRCCS, Milan, Italy. [Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Dept Internal Med, Univ Hosp, CH-1011 Lausanne, Switzerland. [Winkelmann, Bernhard R.] Cardiol Grp, Frankfurt, Germany. [Amouyel, Philippe] Univ Lille Nord France, INSERM, Inst Pasteur Lille, U744, F-59019 Lille, France. [Boehm, Bernhard O.] Univ Hosp, Dept Med, Div Endocrinol & Diabet, Ulm, Germany. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Cusi, Daniele] Fdn Filarete, Milan, Italy. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Hveem, Kristian] Norwegian Univ Sci & Technol, Helseundersokelsen Nord Trondelag HUNT Res Ctr, Dept Publ Hlth & Gen Practice, Levanger, Norway. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta; Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Bioctr, Oulu, Finland. [Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Comprehens Canc Ctr East, Nijmegen, Netherlands. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Levinson, Douglas F.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Clin Med, Tromso, Norway. [Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands. [Penninx, Brenda] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA. [Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England. [Sorensen, Thorkild I. A.] Bispebjerg Hosp, Inst Prevent Med, Copenhagen, Denmark. [Sorensen, Thorkild I. A.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. [Uusitupa, Matti; McCarthy, Mark I.] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland. [Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Wichmann, H-Erich; Heid, Iris M.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham Heart Study, Framingham, MA USA. [Groop, Leif C.] Lund Univ, Dept Clin Sci, Ctr Diabet, Malmo, Sweden. [Haritunian, Talin] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Karpe, Fredrik] Churchill Hosp, Oxford NIHR Biomed Res, Oxford OX3 7LJ, England. [O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Schadt, Eric E.] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, New York, NY USA. [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA. [Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England. [Meyre, David] McMaster Univ, Dept Clin Epidemiol & Biostatist, Hamilton, ON, Canada. [Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY USA. RP Ingelsson, E (reprint author), Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. EM erik.ingelsson@medsci.uu.se RI Erdmann, Jeanette/P-7513-2014; Hinney, Anke/D-6953-2011; Evans, David/H-6325-2013; Colaus, PsyColaus/K-6607-2013; Lee, Sang Hong/A-2569-2011; Strawbridge, Rona/H-5422-2012; Deloukas, Panos/B-2922-2013; van der Klauw, Melanie/A-2138-2014; Hypponen, Elina/B-2596-2014; Kiemeney, Lambertus/D-3357-2009; Palmer, Colin/C-7053-2008; Pramstaller, Peter/C-2357-2008; Palmer, Lyle/K-3196-2014; Fall, Tove/O-7226-2014; Medland, Sarah/C-7630-2013; Boehm, Bernhard/F-8750-2015; Grallert, Harald/B-3424-2013; Milani, Lili/C-8759-2011; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Vegt, F./L-4704-2015; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Johansson, Asa/G-5270-2011; Thorand, Barbara/B-5349-2014; Peters, Annette/A-6117-2011; Tregouet, David-Alexandre/E-3961-2016; Vermeulen, H.H.M./L-4716-2015; Rudan, Igor/I-1467-2012; Smith, Albert/K-5150-2015; Yang, Jian/A-5852-2010; Study, GoDARTS/K-9448-2016; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Franke, Lude/P-7036-2016; Wong, Andrew/M-8899-2016; Konig, Inke/A-4544-2009; Magnusson, Patrik/C-4458-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; OI Wheeler, Eleanor/0000-0002-8616-6444; Sinisalo, Juha/0000-0002-0169-5137; Kleber, Marcus/0000-0003-0663-7275; Martin, Nicholas/0000-0003-4069-8020; Ganna, Andrea/0000-0002-8147-240X; Watkins, Hugh/0000-0002-5287-9016; Medina-Gomez, Carolina/0000-0001-7999-5538; Visscher, Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060; Evans, David/0000-0003-0663-4621; Ouwehand, Willem/0000-0002-7744-1790; Scherag, Andre/0000-0002-9406-4704; Kumari, Meena/0000-0001-9716-1035; Kuulasmaa, Kari/0000-0003-2165-1411; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Vandenput, Liesbeth/0000-0002-1712-6131; Karpe, Fredrik/0000-0002-2751-1770; Abecasis, Goncalo/0000-0003-1509-1825; Paternoster, Lavinia/0000-0003-2514-0889; Manunta, Paolo/0000-0003-3976-9696; Erdmann, Jeanette/0000-0002-4486-6231; Lakka, Timo/0000-0002-9199-2871; Ferrario, Marco M/0000-0003-2741-7124; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Franks, Paul/0000-0002-0520-7604; Hinney, Anke/0000-0001-5659-0706; Lee, Sang Hong/0000-0001-9701-2718; Strawbridge, Rona/0000-0001-8506-3585; Deloukas, Panos/0000-0001-9251-070X; van der Klauw, Melanie/0000-0001-7178-009X; Hypponen, Elina/0000-0003-3670-9399; Kiemeney, Lambertus/0000-0002-2368-1326; Palmer, Colin/0000-0002-6415-6560; Palmer, Lyle/0000-0002-1628-3055; Medland, Sarah/0000-0003-1382-380X; Milani, Lili/0000-0002-5323-3102; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Montgomery, Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; Johansson, Asa/0000-0002-2915-4498; Thorand, Barbara/0000-0002-8416-6440; Rudan, Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845; Yang, Jian/0000-0003-2001-2474; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Franke, Lude/0000-0002-5159-8802; Wong, Andrew/0000-0003-2079-4779; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Radhakrishnan, Aparna/0000-0002-8153-9037; Heard-Costa, Nancy/0000-0001-9730-0306; Cupples, L. Adrienne/0000-0003-0273-7965; Shungin, Dmitry/0000-0001-7900-5856; Day, Felix/0000-0003-3789-7651; Magi, Reedik/0000-0002-2964-6011; Peters, Marjolein/0000-0003-3167-9063; Esko, Tonu/0000-0003-1982-6569; Kristiansson, Kati/0000-0003-4688-107X; Willer, Cristen/0000-0001-5645-4966; Rendon, Augusto/0000-0001-8994-0039; TREMOLI, ELENA/0000-0002-0929-6106; sanna, serena/0000-0002-3768-1749; Kivimaki, Mika/0000-0002-4699-5627; Johnson, Toby/0000-0002-5998-3270; van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Hunt, Sarah/0000-0002-8350-1235 FU Aarno Koskelo Foundation; Agency for Science, Technology and Research of Singapore; Australian National Health and Medical Research Council; Australian Research Council; BDA Research; BioSHaRE Consortium; British Heart Foundation; Cedars-Sinai Board of Governors' Chair in Medical Genetics; Centre for Clinical Research at the University of Leipzig; Centre of Excellence in Genomics; University of Tartu; Chief Scientist Office of the Scottish government; City of Kuopio; Social Insurance Institution of Finland; Department of Educational Assistance; University and Research of the Autonomous Province of Bolzano; Donald W. Reynolds Foundation; Dutch Ministry for Health, Welfare and Sports; Dutch Ministry of Education, Culture and Science; Dutch BBRMI-NL; Dutch Brain Foundation; Dutch Centre for Medical Systems Biology; Dutch Diabetes Research Foundation; Dutch Government Economic Structure-Enhancing Fund; Dutch Inter-University Cardiology Institute; Dutch Kidney Foundation; Dutch Ministry of Economic Affairs; Dutch Ministry of Justice; Dutch Research Institute for Diseases in the Elderly; Eleanor Nichols endowments; Emil Aaltonen Foundation; Erasmus Medical Center; Erasmus University; Estonian government; European Commission; European Regional Development Fund; European Research Council; European Science Foundation; Faculty of Biology and Medicine of Lausanne; Finland's Slot Machine Association; Finnish Cultural Foundation; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Funding Agency for Technology and Innovation; Finnish Heart Association; Finnish Medical Society; Finnish Ministry of Education and Culture; Finnish Ministry of Health and Social Affairs; Finnish National Institute for Health and Welfare; Finnish Social Insurance Institution; Finska Lakaresallskapet; Folkhalsan Research Foundation; Foundation for Life and Health in Finland; French Ministry of Research; French National Research Agency; Genetic Association Information Network; German Diabetes Association; German Federal Ministry of Education and Research; German Ministry of Cultural Affairs; German National Genome Research Network; German Research Foundation; GlaxoSmithKline; Goteborg Medical Society; Greek General Secretary of Research and Technology; Gyllenberg Foundation; Health Care Centers in Vasa, Narpes and Korsholm; Heinz Nixdorf Foundation; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; Icelandic Heart Association; Icelandic Parliament; Intramural Research Program of the Division of Cancer Epidemiology and Genetics, the National Cancer Institute, NIH; Italian Ministry of Education, Universities and Research; Italian Ministry of Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; Knut and Alice Wallenberg Foundation; Kuopio, Tampere and Turku University Hospital Medical Funds; Leducq Foundation; Lundberg Foundation; March of Dimes; Munich Center of Health Sciences as part of LMUinnovativ; Municipal Health Care Center and Hospital in Jakobstad; Municipality of Rotterdam; Narpes Health Care Foundation; National Alliance for Research on Schizophrenia and Depression Young Investigator Awards; Netherlands Genomics Initiative; Netherlands Organization for Health Research and Development; UK NHSBT; US National Institutes of Health; Nordic Center of Cardiovascular Research; Nordic Center of Excellence in Disease Genetics; Nordic Centre of Excellence on Systems Biology in Controlled Dietary Interventions and Cohort Studies; Northern Netherlands Collaboration of Provinces; Novo Nordisk Foundation; Ollqvist Foundation; Orion-Farmos Research Foundation; Paavo Nurmi Foundation; Paivikki and Sakari Sohlberg Foundation; Perklen Foundation; Petrus and Augusta Hedlunds Foundation; Province of Groningen; Republic of Croatia Ministry of Science, Education and Sport; Reynold's Foundation; Royal Society; Samfundet Folkhalsan; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Sophia Foundation for Medical Research; South Tyrolean Sparkasse Foundation; Southern California Diabetes Endocrinology Research Center; Stockholm County Council; Strategic Cardiovascular Program of Karolinska Institutet; Strategic Support for Epidemiological Research at Karolinska Institutet; Susan G. Komen Breast Cancer Foundation; Swedish Ministry for Higher Education; Swedish Cancer Society; Swedish Cultural Foundation in Finland; Swedish Diabetes Association; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Medical Research Council; Swedish Ministry of Education; Swedish Research Council; Swedish Royal Academy of Science; Swedish Society for Medical Research; Swedish Society of Medicine; Swiss National Science Foundation; Tampere Tuberculosis Foundation; Great Wine Estates of the Margaret River Region of Western Australia; Paul Michael Donovan Charitable Foundation; Torsten and Ragnar Soderberg Foundation; Cancer Research UK; UK Diabetes Association; UK Heart Foundation; UK MRCUK NIHR, Biomedical Research Centre; UK West Anglia Primary and Community Care; University Medical Center Groningen; University of Groningen; Vastra Gotaland Foundation; VU University: the Institute for Health and Care Research and the Neuroscience Campus Amsterdam; Wellcome Trust; Yrjo Jahnsson Foundation FX A full list of acknowledgments appears in the Supplementary Note. Funding was provided by the Aarno Koskelo Foundation; the Academy of Finland; the Agency for Science, Technology and Research of Singapore; the Australian National Health and Medical Research Council; the Australian Research Council; BDA Research; the BioSHaRE Consortium; the British Heart Foundation; the Cedars-Sinai Board of Governors' Chair in Medical Genetics; the Centre for Clinical Research at the University of Leipzig; the Centre of Excellence in Genomics and the University of Tartu; the Chief Scientist Office of the Scottish government; the City of Kuopio and the Social Insurance Institution of Finland; the Department of Educational Assistance, the University and Research of the Autonomous Province of Bolzano; the Donald W.; Reynolds Foundation; the Dutch Ministry for Health, Welfare and Sports; the Dutch Ministry of Education, Culture and Science; Dutch BBRMI-NL; the Dutch Brain Foundation; the Dutch Centre for Medical Systems Biology; the Dutch Diabetes Research Foundation; the Dutch Government Economic Structure-Enhancing Fund; the Dutch Inter-University Cardiology Institute; the Dutch Kidney Foundation; the Dutch Ministry of Economic Affairs; the Dutch Ministry of Justice; the Dutch Research Institute for Diseases in the Elderly; Eleanor Nichols endowments; the Emil Aaltonen Foundation; Erasmus Medical Center and Erasmus University; the Estonian government; the European Commission; the European Regional Development Fund; the European Research Council; the European Science Foundation; the Faculty of Biology and Medicine of Lausanne; Finland's Slot Machine Association; the Finnish Cultural Foundation; the Finnish Diabetes Research Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Funding Agency for Technology and Innovation; the Finnish Heart Association; the Finnish Medical Society; the Finnish Ministry of Education and Culture; the Finnish Ministry of Health and Social Affairs; the Finnish National Institute for Health and Welfare; the Finnish Social Insurance Institution; Finska Lakaresallskapet; the Folkhalsan Research Foundation; the Foundation for Life and Health in Finland; the French Ministry of Research; the French National Research Agency; the Genetic Association Information Network; the German Diabetes Association; the German Federal Ministry of Education and Research; the German Ministry of Cultural Affairs; the German National Genome Research Network; the German Research Foundation; GlaxoSmithKline; the Goteborg Medical Society; the Greek General Secretary of Research and Technology; the Gyllenberg Foundation; Health Care Centers in Vasa, Narpes and Korsholm; the Heinz Nixdorf Foundation; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; the Icelandic Heart Association; the Icelandic Parliament; the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, the National Cancer Institute, NIH; Italian Ministry of Education, Universities and Research; Italian Ministry of Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; the Knut and Alice Wallenberg Foundation; Kuopio, Tampere and Turku University Hospital Medical Funds; the Leducq Foundation; the Lundberg Foundation; the March of Dimes; the Munich Center of Health Sciences as part of LMUinnovativ; the Municipal Health Care Center and Hospital in Jakobstad; the Municipality of Rotterdam; the Narpes Health Care Foundation; National Alliance for Research on Schizophrenia and Depression Young Investigator Awards; the Netherlands Genomics Initiative; the Netherlands Organization for Health Research and Development; UK NHSBT; US National Institutes of Health; the Nordic Center of Cardiovascular Research; the Nordic Center of Excellence in Disease Genetics; the Nordic Centre of Excellence on Systems Biology in Controlled Dietary Interventions and Cohort Studies; the Northern Netherlands Collaboration of Provinces; the Novo Nordisk Foundation; the Ollqvist Foundation; the Orion-Farmos Research Foundation; the Paavo Nurmi Foundation; the Paivikki and Sakari Sohlberg Foundation; the Perklen Foundation; the Petrus and Augusta Hedlunds Foundation; the Province of Groningen; the Republic of Croatia Ministry of Science, Education and Sport; the Reynold's Foundation; the Royal Society; Samfundet Folk; halsan; the Signe and Ane Gyllenberg Foundation; the Sigrid Juselius Foundation; the Social Ministry of the Federal State of Mecklenburg-West Pomerania; the Sophia Foundation for Medical Research; the South Tyrolean Sparkasse Foundation; the Southern California Diabetes Endocrinology Research Center; the Stockholm County Council; the Strategic Cardiovascular Program of Karolinska Institutet; Strategic Support for Epidemiological Research at Karolinska Institutet; the Susan G. Komen Breast Cancer Foundation; the Swedish Ministry for Higher Education; the Swedish Cancer Society; the Swedish Cultural Foundation in Finland; the Swedish Diabetes Association; the Swedish Foundation for Strategic Research; the Swedish Heart-Lung Foundation; the Swedish Medical Research Council; the Swedish Ministry of Education; the Swedish Research Council; the Swedish Royal Academy of Science; the Swedish Society for Medical Research; the Swedish Society of Medicine; the Swiss National Science Foundation; the Tampere Tuberculosis Foundation; The Great Wine Estates of the Margaret River Region of Western Australia; The Paul Michael Donovan Charitable Foundation; the Torsten and Ragnar Soderberg Foundation; Cancer Research UK; the UK Diabetes Association; the UK Heart Foundation; the UK MRC; the UK NIHR, Biomedical Research Centre; UK West Anglia Primary and Community Care; the University Medical Center Groningen and the University of Groningen; the Vastra Gotaland Foundation; VU University: the Institute for Health and Care Research and the Neuroscience Campus Amsterdam; the Wellcome Trust; and the Yrjo Jahnsson Foundation. NR 54 TC 177 Z9 185 U1 5 U2 103 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2013 VL 45 IS 5 BP 501 EP U69 DI 10.1038/ng.2606 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 133RU UT WOS:000318158200011 PM 23563607 ER PT J AU Chen, O Zhao, J Chauhan, VP Cui, J Wong, C Harris, DK Wei, H Han, HS Fukumura, D Jain, RK Bawendi, MG AF Chen, Ou Zhao, Jing Chauhan, Vikash P. Cui, Jian Wong, Cliff Harris, Daniel K. Wei, He Han, Hee-Sun Fukumura, Dai Jain, Rakesh K. Bawendi, Moungi G. TI Compact high-quality CdSe-CdS core-shell nanocrystals with narrow emission linewidths and suppressed blinking SO NATURE MATERIALS LA English DT Article ID LIGHT-EMITTING-DIODES; CADMIUM SELENIDE NANOCRYSTALS; QUANTUM-DOT BLINKING; SEMICONDUCTOR NANOCRYSTALS; FLUORESCENCE INTERMITTENCY; IN-VIVO; OPTICAL-PROPERTIES; SINGLE; PHOTOLUMINESCENCE; NANOSTRUCTURES AB High particle uniformity, high photoluminescence quantum yields, narrow and symmetric emission spectral lineshapes and minimal single-dot emission intermittency (known as blinking) have been recognized as universal requirements for the successful use of colloidal quantum dots in nearly all optical applications. However, synthesizing samples that simultaneously meet all these four criteria has proven challenging. Here, we report the synthesis of such high-quality CdSe-CdS core-shell quantum dots in an optimized process that maintains a slow growth rate of the shell through the use of octanethiol and cadmium oleate as precursors. In contrast with previous observations, single-dot blinking is significantly suppressed with only a relatively thin shell. Furthermore, we demonstrate the elimination of the ensemble luminescence photodarkening that is an intrinsic consequence of quantum dot blinking statistical ageing. Furthermore, the small size and high photoluminescence quantum yields of these novel quantum dots render them superior in vivo imaging agents compared with conventional quantum dots. We anticipate these quantum dots will also result in significant improvement in the performance of quantum dots in other applications such as solid-state lighting and illumination. C1 [Chen, Ou; Zhao, Jing; Cui, Jian; Wong, Cliff; Harris, Daniel K.; Wei, He; Han, Hee-Sun; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mgb@mit.edu RI Chauhan, Vikash/H-8172-2013 OI Chauhan, Vikash/0000-0001-9126-2302 FU NIH [5-U54-CA119349, 5R01CA126642]; ARO through the Institute for Soldier Nanotechnologies [W911NF-07-D-0004]; NSF [CHE-0714189, DMR-08-19762, CHE-9808061, DBI-9729592] FX The work received support from the NIH through grants 5-U54-CA119349 (M.G.B.) and 5R01CA126642 (M.G.B., D.F., R.K.J.), the ARO through the Institute for Soldier Nanotechnologies (W911NF-07-D-0004), and the NSF through a Collaborative Research in Chemistry Program (CHE-0714189) (M.G.B.). This work made use of the MRSEC Shared Experimental Facilities at MIT, supported by the National Science Foundation under award number DMR-08-19762 and the MIT DCIF NMR spectrometer funded through National Science Foundation Grants CHE-9808061 and DBI-9729592. NR 52 TC 339 Z9 341 U1 42 U2 464 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1476-1122 EI 1476-4660 J9 NAT MATER JI Nat. Mater. PD MAY PY 2013 VL 12 IS 5 BP 445 EP 451 DI 10.1038/NMAT3539 PG 7 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 130XY UT WOS:000317954800016 PM 23377294 ER PT J AU Lu, BX Al-Ramahi, I Valencia, A Wang, Q Berenshteyn, F Yang, HD Gallego-Flores, T Ichcho, S Lacoste, A Hild, M DiFiglia, M Botas, J Palacino, J AF Lu, Boxun Al-Ramahi, Ismael Valencia, Antonio Wang, Qiong Berenshteyn, Frada Yang, Haidi Gallego-Flores, Tatiana Ichcho, Salah Lacoste, Arnaud Hild, Marc DiFiglia, Marian Botas, Juan Palacino, James TI Identification of NUB1 as a suppressor of mutant Huntingtin toxicity via enhanced protein clearance SO NATURE NEUROSCIENCE LA English DT Article ID GENE HOMOLOG HDH; IN MOUSE MODEL; PROTEASOMAL DEGRADATION; DISEASE PROGRESSION; CELLS; NEDD8; NEUROPATHOLOGY; EXPRESSION; MODIFIERS; MOTOR AB Huntington's disease is caused by expanded CAG repeats in HTT, conferring toxic gain of function on mutant HTT (mHTT) protein. Reducing mHTT amounts is postulated as a strategy for therapeutic intervention. We conducted genome-wide RNA interference screens for genes modifying mHTT abundance and identified 13 hits. We tested 10 in vivo in a Drosophila melanogaster Huntington's disease model, and 6 exhibited activity consistent with the in vitro screening results. Among these, negative regulator of ubiquitin-like protein 1 (NUB1) overexpression lowered mHTT in neuronal models and rescued mHTT-induced death. NUB1 reduces mHTT amounts by enhancing polyubiquitination and proteasomal degradation of mHTT protein. The process requires CUL3 and the ubiquitin-like protein NEDD8 necessary for CUL3 activation. As a potential approach to modulating NUB1 for treatment, interferon-beta lowered mHTT and rescued neuronal toxicity through induction of NUB1. Thus, we have identified genes modifying endogenous mHTT using high-throughput screening and demonstrate NUB1 as an exemplar entry point for therapeutic intervention of Huntington's disease. C1 [Lu, Boxun] Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China. [Lu, Boxun; Wang, Qiong; Berenshteyn, Frada; Yang, Haidi; Ichcho, Salah; Lacoste, Arnaud; Hild, Marc; Palacino, James] Novartis Inst BioMed Res Inc, Dev & Mol Pathways, Cambridge, MA USA. [Al-Ramahi, Ismael; Gallego-Flores, Tatiana; Botas, Juan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Al-Ramahi, Ismael; Gallego-Flores, Tatiana; Botas, Juan] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Valencia, Antonio; DiFiglia, Marian] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Valencia, Antonio; DiFiglia, Marian] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. RP Palacino, J (reprint author), Novartis Inst BioMed Res Inc, Dev & Mol Pathways, Cambridge, MA USA. EM luboxun@fudan.edu.cn; james.palacino@novartis.com RI Al-Ramahi, Ismael/B-4000-2017 OI Al-Ramahi, Ismael/0000-0002-1275-1114 FU John J. Wasmuth postdoctoral fellowship from the Hereditary Disease Foundation; Hereditary Disease Foundation; US National Institutes of Health grant [NS074381] FX The authors wish to thank D. Curtis for discussions and suggestions during the project, X. Shi for performing the control screening on SMN level changes, C. Mazur for assistance with cloning and sample processing, P. Manos and C. Littlefield for assistance with the hESC and human iPSC experiments, and E. Kim for assistance with the fly experiments. I.A. was funded by a John J. Wasmuth postdoctoral fellowship from the Hereditary Disease Foundation. A.V. was funded by the Hereditary Disease Foundation. M.D. was funded by US National Institutes of Health grant NS074381. NR 51 TC 27 Z9 28 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2013 VL 16 IS 5 BP 562 EP + DI 10.1038/nn.3367 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 131WT UT WOS:000318029300012 PM 23525043 ER PT J AU Patel, SR Sheth, SA Martinez-Rubio, C Mian, MK Asaad, WF Gerrard, JL Kwon, CS Dougherty, DD Flaherty, AW Greenberg, BD Gale, JT Williams, ZM Eskandar, EN AF Patel, Shaun R. Sheth, Sameer A. Martinez-Rubio, Clarissa Mian, Matthew K. Asaad, Wael F. Gerrard, Jason L. Kwon, Churl-Su Dougherty, Darin D. Flaherty, Alice W. Greenberg, Benjamin D. Gale, John T. Williams, Ziv M. Eskandar, Emad N. TI Studying task-related activity of individual neurons in the human brain SO NATURE PROTOCOLS LA English DT Article ID SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; BEHAVIORAL-CONTROL; MICROELECTRODE; RESPONSES; STIMULATION; PATHOPHYSIOLOGY; POTENTIALS AB Single-neuronal studies remain the gold standard for studying brain function. Here we describe a protocol for studying task-related single-neuronal activity in human subjects during neurosurgical procedures involving microelectrode recordings. This protocol has two phases: a preoperative phase and an intraoperative phase. During the preoperative phase, we discuss informed consent, equipment setup and behavioral testing. During the intraoperative phase, we discuss the procedure for microelectrode recordings. Because patients are often awake during these procedures, this protocol can be performed in conjunction with behavioral tasks for studying a variety of cognitive functions. We describe the protocol in detail and provide two examples of expected results. In addition, we discuss the potential difficulties and pitfalls related to intraoperative studies. This protocol takes similar to 1.5 h to complete. C1 [Patel, Shaun R.; Martinez-Rubio, Clarissa; Mian, Matthew K.; Kwon, Churl-Su; Williams, Ziv M.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Patel, Shaun R.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Sheth, Sameer A.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Neurosurg, New York, NY USA. [Asaad, Wael F.] Brown Univ, Alpert Med Sch, Brown Inst Brain Sci, Dept Neurosurg, Providence, RI 02912 USA. [Gerrard, Jason L.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Dougherty, Darin D.; Flaherty, Alice W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Flaherty, Alice W.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Greenberg, Benjamin D.] Brown Univ, Alpert Med Sch, Brown Inst Brain Sci, Dept Psychiat, Providence, RI 02912 USA. [Gale, John T.] Cleveland Clin, Dept Neurosci, Cleveland, OH USA. [Gale, John T.] Cleveland Clin, Ctr Neurol Restorat, Cleveland, OH USA. RP Patel, SR (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM shaun.patel@me.com RI Asaad, Wael/I-8485-2012 OI Asaad, Wael/0000-0003-4406-9096 FU US National Institutes of Health (NIH) (National Institute on Drug Abuse (NIDA) [R01DA026297]; National Eye Institute (NEI) [NEI 1R01EY017658-01A1]; National Institute of Mental Health (NIMH) [MH086400]; Klingenstein Foundation; Howard Hughes Medical Institute; Dana Foundation; Sackler Programme in Psychobiology; National Institute of Neurological Disorders and Stroke (NINDS) [R25 NS065743] FX This work was supported by grants from the US National Institutes of Health (NIH) (National Institute on Drug Abuse (NIDA) no. R01DA026297). E.N.E. was supported by National Eye Institute (NEI) grant no. NEI 1R01EY017658-01A1, the National Institute of Mental Health (NIMH) Conte Award no. MH086400, the Klingenstein Foundation, the Howard Hughes Medical Institute and the Dana Foundation. S.R.P. was supported by the Sackler Programme in Psychobiology. S.A.S. was supported by National Institute of Neurological Disorders and Stroke (NINDS) grant no. R25 NS065743. We thank K. Finnis for providing the 3D reconstructions. NR 29 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD MAY PY 2013 VL 8 IS 5 BP 949 EP 957 DI 10.1038/nprot.2013.050 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 133PJ UT WOS:000318151000010 PM 23598445 ER PT J AU Woods, DC Tilly, JL AF Woods, Dori C. Tilly, Jonathan L. TI Isolation, characterization and propagation of mitotically active germ cells from adult mouse and human ovaries SO NATURE PROTOCOLS LA English DT Article ID STEM-CELLS; TRANSCRIPTION FACTOR; IN-VITRO; RETINOIC ACID; PROTEIN; MICE; DIFFERENTIATION; TRANSPLANTATION; EXPRESSION; OOCYTES AB Accruing evidence indicates that production of new oocytes (oogenesis) and their enclosure by somatic cells (folliculogenesis) are processes not limited to the perinatal period in mammals. Endpoints ranging from oocyte counts to genetic lineage tracing and transplantation experiments support a paradigm shift in reproductive biology involving active renewal of oocyte-containing follicles during postnatal life. The recent purification of mitotically active oocyte progenitor cells, termed female germline stem cells (fGSCs) or oogonial stem cells (OSCs), from mouse and human ovaries opens up new avenues for research into the biology and clinical utility of these cells. Here we detail methods for the isolation of mouse and human OSCs from adult ovarian tissue, cultivation of the cells after purification, and characterization of the cells before and after ex vivo expansion. The latter methods include analysis of germ cell-specific markers and in vitro oogenesis, as well as the use of intraovarian transplantation to test the oocyte-forming potential of OSCs in vivo. C1 [Woods, Dori C.; Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Tilly, JL (reprint author), Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jtilly@partners.org FU Method to Extend Research in Time (MERIT) Award from the National Institute on Aging (National Institutes of Health (NIH)) [R37-AG012279]; Ruth L. Kirschstein National Research Service Award [NIH F32-AG034809]; Glenn Foundation Award for Research in the Biological Mechanisms of Aging; Henry and Vivian Rosenberg Philanthropic Fund FX This work conducted by the authors and discussed herein was supported by a Method to Extend Research in Time (MERIT) Award from the National Institute on Aging (National Institutes of Health (NIH) R37-AG012279 to J.L.T.), a Ruth L. Kirschstein National Research Service Award (NIH F32-AG034809 to D.C.W.), a Glenn Foundation Award for Research in the Biological Mechanisms of Aging (J.L.T.) and the Henry and Vivian Rosenberg Philanthropic Fund (J.L.T.). We thank L. Prickett-Rice and K. Folz-Donahue of the Harvard Stem Cell Institute for outstanding technical assistance with flow cytometry, and M. Cooper (Cooper Graphics) for expert assistance with preparation of Figure 1. NR 57 TC 41 Z9 44 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD MAY PY 2013 VL 8 IS 5 BP 966 EP 988 DI 10.1038/nprot.2013.047 PG 23 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 133PJ UT WOS:000318151000012 PM 23598447 ER PT J AU Travis, LB Wahnefried, WD Allan, JM Wood, ME Ng, AK AF Travis, Lois B. Wahnefried, Wendy Demark Allan, James M. Wood, Marie E. Ng, Andrea K. TI Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC-CELL TRANSPLANTATION; LONG-TERM SURVIVORS; CONTRALATERAL BREAST-CANCER; NON-HODGKINS-LYMPHOMA; 2ND PRIMARY TUMORS; CHRONIC LYMPHOCYTIC-LEUKEMIA; WOMENS ENVIRONMENTAL CANCER; SURGICAL ADJUVANT BREAST AB Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA, superseding first primary cancers of the breast, lung, and prostate. The occurrence of second malignant neoplasms (SMN) is influenced by a myriad of factors, including the late effects of cancer therapy, shared aetiological factors with the primary cancer ( such as tobacco use, excessive alcohol intake, and obesity), genetic predisposition, environmental determinants, host effects, and combinations of factors, including gene-environment interactions. The influence of these factors on SMN in survivors of adult-onset cancer is reviewed here. We also discuss how modifiable behavioural and lifestyle factors may contribute to SMN, and how these factors can be managed. Cancer survivorship provides an opportune time for oncologists and other health-care providers to counsel patients with regard to health promotion, not only to reduce SMN risk, but to minimize co-morbidities. In particular, the importance of smoking cessation, weight control, physical activity, and other factors consonant with adoption of a healthy lifestyle should be consistently emphasized to cancer survivors. Clinicians can also play a critical role by endorsing genetic counselling for selected patients and making referrals to dieticians, exercise trainers, and others to assist with lifestyle change interventions. C1 [Travis, Lois B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. [Travis, Lois B.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA. [Wahnefried, Wendy Demark] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Allan, James M.] Newcastle Univ, Newcastle Canc Ctr, Northern Inst Canc Res, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Wood, Marie E.] Univ Vermont, Dept Med, Div Hematol Oncol, Burlington, VT 05405 USA. [Ng, Andrea K.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Ng, Andrea K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Travis, LB (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. EM lois_travis@urmc.rochester.edu RI Allan, James/B-4448-2009 NR 207 TC 45 Z9 46 U1 1 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2013 VL 10 IS 5 BP 289 EP 301 DI 10.1038/nrclinonc.2013.41 PG 13 WC Oncology SC Oncology GA 133RM UT WOS:000318157200007 PM 23529000 ER PT J AU Cosyns, SMR Dhaese, I Thoonen, R Buys, ES Vral, A Brouckaert, P Lefebvre, RA AF Cosyns, S. M. R. Dhaese, I. Thoonen, R. Buys, E. S. Vral, A. Brouckaert, P. Lefebvre, R. A. TI Heme deficiency of soluble guanylate cyclase induces gastroparesis SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE gastrointestinal motility; nitric oxide; soluble guanylate cyclase ID VASOACTIVE INTESTINAL POLYPEPTIDE; RAT GASTRIC FUNDUS; MOUSE DISTAL COLON; NITRIC-OXIDE; KNOCKOUT MICE; INHIBITORY NEUROTRANSMISSION; LONGITUDINAL MUSCLE; MOTILITY; TRANSIT; HYPERTENSION AB Background Soluble guanylate cyclase (sGC) is the principal target of nitric oxide (NO) to control gastrointestinal motility. The consequence on nitrergic signaling and gut motility of inducing a heme-free status of sGC, as induced by oxidative stress, was investigated. Methods sGC1H105F knock-in (apo-sGC) mice, which express heme-free sGC that has basal activity, but cannot be stimulated by NO, were generated. Key Results Diethylenetriamine NONOate did not increase sGC activity in gastrointestinal tissue of apo-sGC mice. Exogenous NO did not induce relaxation in fundic, jejunal and colonic strips, and pyloric rings of apo-sGC mice. The stomach was enlarged in apo-sGC mice with hypertrophy of the muscularis externa of the fundus and pylorus. In addition, gastric emptying and intestinal transit were delayed and whole-gut transit time was increased in the apo-sGC mice, while distal colonic transit time was maintained. The nitrergic relaxant responses to electrical field stimulation at 14Hz were abolished in fundic and jejunal strips from apo-sGC mice, but in pyloric rings and colonic strips, only the response at 1Hz was abolished, indicating the contribution of other transmitters than NO. Conclusions & Inferences The results indicate that the gastrointestinal consequences of switching from a native sGC to a heme-free sGC, which cannot be stimulated by NO, are most pronounced at the level of the stomach establishing a pivotal role of the activation of sGC by NO in normal gastric functioning. In addition, delayed intestinal transit was observed, indicating that nitrergic activation of sGC also plays a role in the lower gastrointestinal tract. C1 [Cosyns, S. M. R.; Dhaese, I.; Lefebvre, R. A.] Univ Ghent, Heymans Inst Pharmacol, B-9000 Ghent, Belgium. [Thoonen, R.; Brouckaert, P.] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. [Thoonen, R.] Mol Cardiol Res Ctr, Tufts Med Ctr, Boston, MA USA. [Buys, E. S.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res,Med Sch, Boston, MA USA. [Vral, A.] Univ Ghent, Dept Med Basic Sci, B-9000 Ghent, Belgium. RP Lefebvre, RA (reprint author), Univ Ghent, Heymans Inst Pharmacol, De Pintelaan 185, B-9000 Ghent, Belgium. EM romain.lefebvre@ugent.be FU Special Investigation Fund of Ghent University [BOF10/GOA/024]; Fund of Scientific Research Flanders [G.0021.09N]; COST action (European Network on Gasotransmitters) [BM1005] FX This study was financially supported by grant BOF10/GOA/024 from the Special Investigation Fund of Ghent University, grant G.0021.09N from the Fund of Scientific Research Flanders, and by COST action BM1005 (European Network on Gasotransmitters). NR 50 TC 8 Z9 8 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2013 VL 25 IS 5 BP e339 EP e352 DI 10.1111/nmo.12120 PG 14 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 132DP UT WOS:000318048400004 PM 23551931 ER PT J AU Napadow, V Sheehan, J Kim, J Dassatti, A Thurler, AH Surjanhata, B Vangel, M Makris, N Schaechter, JD Kuo, B AF Napadow, V. Sheehan, J. Kim, J. Dassatti, A. Thurler, A. H. Surjanhata, B. Vangel, M. Makris, N. Schaechter, J. D. Kuo, B. TI Brain white matter microstructure is associated with susceptibility to motion-induced nausea SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE brain imaging; diffusion tensor imaging; nausea; neuroplasticity AB Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of the heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion-induced nausea are due to microstructural differences in the inferior fronto-occipital fasciculus (IFOF), the white matter tract connecting the right visual motion processing area (MT+/V5) and right anterior insula. To test this hypothesis, we acquired diffusion tensor imaging data from 30 healthy adults who were subsequently dichotomized into high and low nausea susceptibility groups based on the Motion Sickness Susceptibility Scale. We quantified diffusion along the IFOF for each subject based on axial diffusivity (AD); radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA), and evaluated between-group differences in these diffusion metrics. Subjects with high susceptibility to nausea rated significantly (P<0.001) higher nausea intensity to visual motion stimuli and had significantly (P<0.05) lower AD and MD along the right IFOF compared to subjects with low susceptibility to nausea. This result suggests that differences in white matter microstructure within tracts connecting visual motion and nausea-processing brain areas may contribute to nausea susceptibility or may have resulted from an increased history of nausea episodes. C1 [Napadow, V.; Kim, J.; Vangel, M.; Schaechter, J. D.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Sheehan, J.; Dassatti, A.; Thurler, A. H.; Surjanhata, B.; Kuo, B.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Makris, N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, 2301 149 13th St, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu FU National Institutes of Health [K01-AT002166, P01-AT006663, R01-AT004714, K23-DK069614, R21-DK097499]; National Center for Research Resources (Harvard Clinical and Translational Science Center) [P41RR14075, CRC 1 UL1 RR025758]; International Foundation of Functional Gastrointestinal Disorders FX This work was supported by the National Institutes of Health (grant numbers K01-AT002166, P01-AT006663, and R01-AT004714 to VN, K23-DK069614 to BK, and R21-DK097499 to both VN and BK); the National Center for Research Resources (P41RR14075; CRC 1 UL1 RR025758, Harvard Clinical and Translational Science Center); and the International Foundation of Functional Gastrointestinal Disorders. The content is solely the responsibility of the authors and does not necessarily represent the official views of our sponsors. NR 8 TC 9 Z9 9 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2013 VL 25 IS 5 DI 10.1111/nmo.12084 PG 4 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 132DP UT WOS:000318048400017 PM 23360260 ER PT J AU Rodriguez, L Roberts, LD Larosa, J Heinz, N Gerszten, R Nurko, S Goldstein, AM AF Rodriguez, L. Roberts, L. D. Larosa, J. Heinz, N. Gerszten, R. Nurko, S. Goldstein, A. M. TI Relationship between postprandial metabolomics and colon motility in children with constipation SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE Children; Colon motility; Constipation; Metabolomic profile ID FUNCTIONAL GASTROINTESTINAL DISORDERS; ACTIVATION; RESPONSES; HUMANS; RATS AB Background The metabolic pathways associated with colonic motility are unknown. To identify potential metabolic targets for treatment of constipation, we examined the metabolic profile before and after a meal challenge in a cohort of children with constipation and determined its relationship with postprandial colon motility patterns. Methods In this prospective study, 187 metabolites were measured by liquid chromatographymass spectrometry at multiple time points before and after a standardized meal in constipated children undergoing a colon manometry. Postprandial metabolite levels were compared with baseline and also correlated with multiple manometric measurements, including the number, frequency, and amplitude of pressure peaks as well as the motility index (MI). Key Results A total of 20 subjects were included (mean age 13.1 +/- 3.4years). No significant metabolite changes were observed at 10min after the meal, whereas 16 amino acid and 22 lipid metabolites had significant (P<0.005) postprandial changes, including decreases in methylhistamine, histamine, and GABA, by 60min. Correlations were observed between normal and abnormal postprandial motility patterns and changes in specific metabolites, including glycerol, carnosine, alanine, asparagine, cytosine, choline, phosphocholine, thyroxine, and triiodothyronine. Interestingly, subjects without the normal postprandial increase in area under the curve (AUC), had markedly increased levels of kynurenic acid and adenosyl-homocysteine. Conclusions & Inferences This is the first study to examine postprandial metabolic changes in children and also to correlate changes in specific metabolites with colonic motility. The results suggest possible metabolic pathways associated with motility and identify potential targets for the treatment of constipation. C1 [Rodriguez, L.; Roberts, L. D.; Larosa, J.; Heinz, N.; Nurko, S.] Harvard Univ, Sch Med, Ctr Motil & Funct Gastrointestinal Disorders, Div Gastroenterol,Childrens Hosp Boston, Boston, MA USA. [Roberts, L. D.; Gerszten, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. [Goldstein, A. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. RP Rodriguez, L (reprint author), Childrens Hosp, Ctr Motil & Funct Gastrointestinal Disorders, Div Gastroenterol, 300 Longwood Ave, Boston, MA 02115 USA. EM leonel.rodriguez@childrens.harvard.edu OI Roberts, Lee/0000-0002-1455-5248 FU Harvard Clinical and Translational Center Award [UL1 RR025758-01] FX This study was funded by a Harvard Clinical and Translational Center Award (UL1 RR025758-01). NR 29 TC 2 Z9 3 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAY PY 2013 VL 25 IS 5 DI 10.1111/nmo.12086 PG 8 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 132DP UT WOS:000318048400014 PM 23421516 ER PT J AU Hookway, LA Fuhr, P Frazier, M AF Hookway, Larry Allen Fuhr, Patti Frazier, Marcela TI Use of Ready-Made Spectacles to Meet Visual Needs in a Low-Resource Adult Population SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE humanitarian eye care; vision correction; presbyopia; refractive error; readers; functional vision; spectacles; vision; uncorrected refractive error; visual impairment; blindness ID WILLINGNESS-TO-PAY; UNCORRECTED PRESBYOPIA; REFRACTIVE ERROR; RURAL TANZANIA; EYE DISEASE; IMPAIRMENT; CARE; COUNTRIES; BLINDNESS; PACIFIC AB Purpose. In affluent societies, distance and near vision problems are typically corrected with custom-made eyeglasses. Many persons in less affluent areas do not have the resources for such. The purpose of this study was to assess the use of less expensive ready-made (RM) bifocals and readers to correct distance and near refractive error and presbyopia in an outreach clinic in Nicaragua. Methods. This is a retrospective review of records of all patients older than 34 years who presented for an eye examination in an outreach clinic in Granada, Nicaragua, in 2010. A visual satisfaction questionnaire had been administered to patients before they were examined and after RM plus sphere bifocals or plus sphere reading spectacles were dispensed. The main outcome measures included pre- and post-distance and near visual acuities, vision satisfaction and difficulty ratings, and perceived cost and willingness to pay for replacement rating. Results. Ready-made plus sphere spectacles (bifocals or single-vision readers) were dispensed to 95.4% of those examined. The remaining 4.6% required custom prescriptions because of astigmatism, myopia, or anisometropia. The RM bifocals were very well accepted, with high visual satisfaction ratings with the bifocals improving from a presenting value of 11 to 89.4% at distance and from 6.6 to 89.4% at near. Percentage of patients achieving visual acuity of 20/40 or better improved from 60 to 84.5% at distance and from 44 to 97% at near. Percentage achieving functionally good near vision (20/40 or better) improved from 38 to 97% with RM readers. Patients reporting highest satisfaction with near vision improved from 6.3 to 86.6%. Patients indicated that, on average, they would be willing to pay US$ 18.39 to replace the bifocals and US$ 16.67 to replace the readers. Conclusions. Ready-made bifocals and RM single-vision readers may be an acceptable and affordable alternative for many patients with hyperopia and/or presbyopia where access to custom-made eyeglasses is difficult. (Optom Vis Sci 2013; 90: 494-500) C1 [Hookway, Larry Allen] NOVA Southeastern Coll Optometry, Ft Lauderdale, FL USA. [Fuhr, Patti; Frazier, Marcela] Univ Alabama Birmingham, Sch Optometry, Dept Optometry, Birmingham, AL 35294 USA. [Fuhr, Patti] Birmingham VA Med Ctr, Blind Rehabil Ctr, Birmingham, AL USA. RP Hookway, LA (reprint author), 320 W Walton St,POB 270, Willard, OH 44890 USA. EM larryhookway@gmail.com NR 29 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD MAY PY 2013 VL 90 IS 5 BP 494 EP 500 DI 10.1097/OPX.0b013e31828dedf6 PG 7 WC Ophthalmology SC Ophthalmology GA 131TW UT WOS:000318020300015 PM 23584487 ER PT J AU Winters-Stone, KM Dobek, J Nail, LM Bennett, JA Leo, MC Torgrimson-Ojerio, B Luoh, SW Schwartz, A AF Winters-Stone, K. M. Dobek, J. Nail, L. M. Bennett, J. A. Leo, M. C. Torgrimson-Ojerio, B. Luoh, S. -W. Schwartz, A. TI Impact plus resistance training improves bone health and body composition in prematurely menopausal breast cancer survivors: a randomized controlled trial SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Chemotherapy; Neoplasm; Obesity; Osteoporosis; Physical activity ID MINERAL DENSITY; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; OVARIAN FAILURE; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; FRACTURE RISK; WEIGHT-GAIN; EXERCISE; ESTROGEN AB Our randomized controlled trial in prematurely menopausal breast cancer survivors showed that impact + resistance training prevented increases in percentage of body fat compared with controls and also improved BMD at the hip and prevented BMD loss at the spine among exercise-trained women who were menopausal for > 1 year. Cancer treatment-related menopause worsens bone health and body composition in breast cancer survivors (BCS). We investigated whether impact + resistance training could improve bone mineral density (BMD), reduce bone turnover, build muscle, and decrease fat mass in BCS with premature menopause. We conducted a randomized controlled trial in 71 BCS (mean age, 46.5 years) within 5 years of treatment-related menopause. Women were randomly assigned to one of two groups: (1) impact + resistance training (prevent osteoporosis with impact + resistance (POWIR)) or (2) exercise placebo (FLEX) 3x/week for 1 year. Outcomes were hip and spine BMD (in grams per square centimeter) and body composition (percent body fat (%BF) and lean and fat mass (in kilograms)) by DXA and bone turnover markers (serum osteocalcin (in nanograms per milliliter) and urinary deoxypryrodinoline (in nanomoles per milliliter). There were no significant group x time interactions for bone outcomes when using an intent-to-treat approach on the full sample. In analyses restricted to BCS who were menopausal for a parts per thousand yen1 year, POWIR increased BMD at the hip and slowed BMD loss at the spine compared with FLEX (femoral neck-POWIR, 0.004 +/- 0.093 g/cm(2) vs. FLEX, -0.010 +/- 0.089 g/cm(2); p < 0.01; spine-POWIR, -0.003 +/- 0.114 g/cm(2) vs. FLEX, -0.020 +/- 0.110 g/cm(2); p = 0.03). POWIR prevented increases in %BF (POWIR, 0.01 % vs. FLEX, 1.3 %; p < 0.04). Women with attendance to POWIR at a parts per thousand yen64 % had better improvements in %BF than women attending less often (p < 0.03). Impact + resistance training may effectively combat bone loss and worsening body composition from premature menopause in BCS. C1 [Winters-Stone, K. M.; Dobek, J.; Nail, L. M.; Bennett, J. A.; Torgrimson-Ojerio, B.] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA. [Dobek, J.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. [Winters-Stone, K. M.; Nail, L. M.; Bennett, J. A.] Oregon Hlth & Sci Univ, Knight Canc Ctr, Portland, OR 97239 USA. [Luoh, S. -W.] Portland VA Med Ctr, Portland, OR USA. [Leo, M. C.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Schwartz, A.] Idaho State Univ, Pocatello, ID 83209 USA. [Winters-Stone, K. M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Winters-Stone, KM (reprint author), Oregon Hlth & Sci Univ, 3455 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM wintersk@ohsu.edu FU American Cancer Society Research Scholar Grant [RSGPB-06-092-01-CPPB] FX Funding was provided by an American Cancer Society Research Scholar Grant (RSGPB-06-092-01-CPPB). We thank the Oregon State Cancer Registry for their assistance with recruitment; Thera-band, Inc. for providing elastic exercise bands; and our research assistants, exercise trainers, and participants. NR 45 TC 25 Z9 26 U1 2 U2 37 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2013 VL 24 IS 5 BP 1637 EP 1646 DI 10.1007/s00198-012-2143-2 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 135HV UT WOS:000318280100011 PM 22996743 ER PT J AU Heist, EK Perna, F Chalhoub, F Danik, S Barrett, C Houghtaling, C Tondo, C Mahapatra, S Ruskin, J Mansour, M AF Heist, E. Kevin Perna, Francesco Chalhoub, Fadi Danik, Stephan Barrett, Conor Houghtaling, Christopher Tondo, Claudio Mahapatra, Srijoy Ruskin, Jeremy Mansour, Moussa TI Comparison of Electroanatomical Mapping Systems: Accuracy in Left Atrial Mapping SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE ablation; atrial fibrillation; electrophysiologyclinical; mapping ID CATHETER ABLATION; IMAGE INTEGRATION; FIBRILLATION AB Background Current 3D mapping systems have difficulty rendering complex cardiac structures. Different electroanatomical mapping software has been recently developed which uses a mathematical algorithm to improve interpolation between mapped points and delineation of closely spaced structures. This study tested the feasibility and accuracy of this software in comparison to traditional software. Methods In vivo 3D impedance-based mapping using a multielectrode catheter with a single geometry point cloud was performed in the left atria and pulmonary veins (PV) in 23 patients undergoing catheter ablation for atrial fibrillation. The maps were analyzed with traditional (NavX, St. Jude Medical, Minnetonka, MN, USA), either with or without multichamber mapping versus St. Jude OneModel software and dimensions of cardiac chambers in human studies were compared to preprocedural computed tomographic (CT) or magnetic resonance (MR) scans to determine the relative accuracy of the maps. Results Maps created by the OneModel software provided greater detail of complex cardiac structures compared to traditional software. Comparison of the left atrial/pulmonary vein electroanatomical maps with the CT and MR scans as reference standard demonstrated significantly less error in measurement of all PV ostial long- and short-axis dimensions, inter-PV distance, and ridge width (left PV to left atrial appendage) with the OneModel versus traditional software (P < 0.001 for all dimensions measured). Conclusions The OneModel software produces maps that are more accurate in rendering complex cardiac structures compared to traditional software. C1 [Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org OI Perna, Francesco/0000-0002-9019-9492 NR 13 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 EI 1540-8159 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 2013 VL 36 IS 5 BP 626 EP 631 DI 10.1111/pace.12095 PG 6 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 134SD UT WOS:000318233800022 PM 23437794 ER PT J AU Ahluwalia, SC Levin, JR Lorenz, KA Gordon, HS AF Ahluwalia, Sangeeta C. Levin, Jennifer R. Lorenz, Karl A. Gordon, Howard S. TI "There's no cure for this condition": How physicians discuss advance care planning in heart failure SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Communication; Qualitative; Advance care planning; Heart failure ID BREAKING-BAD-NEWS; LIFE-SUSTAINING TREATMENT; COMMUNICATION-SKILLS; OF-LIFE; SIMULATED INTERVIEWS; MEDICAL-STUDENTS; RANDOMIZED-TRIAL; CANCER CARE; PREFERENCES; END AB Objective: To evaluate the extent to which physicians engage in recommended elements of advance care planning (ACP) communication during outpatient clinic visits with heart failure (HF) patients. Methods: We conducted a qualitative content analysis of 71 audio-recorded and transcribed outpatient visits with 52 patients >= 65 years recently hospitalized for HF and their physicians (n = 44). Results: We identified 25 instances of ACP-related communication over 15 of the 71 visits: in 17 instances, physicians explained the nature of HF but only once was the life-limiting potential of HF Mentioned. Physicians discussed goals of care in 6 instances but elicited their patients' preferences in only 2 of those instances. Finally, physicians encouraged documentation of preferences in 2 instances. Conclusions: Despite recommendations for early ACP with HF patients, physicians rarely engaged in fundamental elements of ACP discussions during outpatient visits. We suggest a stepwise approach to supporting the process of ACP communication in practice. Practice implications: Given the importance of ACP in helping patients plan for their future care, outpatient clinicians should be helped to incorporate these discussions in the routine care of their HF patients. Using a simple heuristic might help physicians engage in fundamental elements of ACP during busy outpatient visits. Published by Elsevier Ireland Ltd. C1 [Ahluwalia, Sangeeta C.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA 90064 USA. [Ahluwalia, Sangeeta C.; Levin, Jennifer R.; Lorenz, Karl A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90064 USA. [Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gordon, Howard S.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA. [Gordon, Howard S.] VA Ctr Management Complex Chron Care, Chicago, IL USA. [Gordon, Howard S.] Univ Illinois, Coll Med, Dept Med, Chicago, IL USA. RP Ahluwalia, SC (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111-G, Los Angeles, CA 90064 USA. EM sangeeta.ahluwalia@va.gov RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU VA Health Services Research and Development (HSR&D), Department of Veterans Affairs [ECV-02-254]; Office of Academic Affiliation's VA Associated Health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence FX Supported in part by grant ECV-02-254 from VA Health Services Research and Development (HSR&D), Department of Veterans Affairs. Dr. Ahluwalia is supported by an Office of Academic Affiliation's VA Associated Health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence. NR 45 TC 9 Z9 9 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAY PY 2013 VL 91 IS 2 BP 200 EP 205 DI 10.1016/j.pec.2012.12.016 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 136AA UT WOS:000318330600011 PM 23369373 ER PT J AU Yang, E Diers, JR Huang, YY Hamblin, MR Lindsey, JS Bocian, DF Holten, D AF Yang, Eunkyung Diers, James R. Huang, Ying-Ying Hamblin, Michael R. Lindsey, Jonathan S. Bocian, David F. Holten, Dewey TI Molecular Electronic Tuning of Photosensitizers to Enhance Photodynamic Therapy: Synthetic Dicyanobacteriochlorins as a Case Study SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CENTRAL METAL; BACTERIOCHLORINS; OXYGEN; SUBSTITUENTS; PORPHYRINS; GENERATION; SPECTRA; SENSITIZERS; MELANOMA; EFFICACY AB Photophysical, photostability, electrochemical and molecular-orbital characteristics are analyzed for a set of stable dicyanobacteriochlorins that are promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc (NC)2BC-Zn and palladium chelate (NC)2BC-Pd. The order of PDT activity against HeLa human cancer cells in vitro is (NC)2BC-Pd>(NC)2BC>(NC)2BC-Zn approximate to BC. The near-infrared absorption feature of each dicyanobacteriochlorin is bathochromically shifted 3550nm (748763nm) from that for BC (713nm). Intersystem crossing to the PDT-active triplet excited state is essentially quantitative for (NC)2BC-Pd. Phosphorescence from (NC)2BC-Pd occurs at 1122nm (1.1eV). This value and the measured ground-state redox potentials fix the triplet excited-state redox properties, which underpin PDT activity via Type-1 (electron transfer) pathways. A perhaps counterintuitive (but readily explicable) result is that of the three dicyanobacteriochlorins, the photosensitizer with the shortest triplet lifetime (7s), (NC)2BC-Pd has the highest activity. Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins studied recently are investigated and discussed in terms of four phenomena: aggregation, reduction, oxidation and chemical reaction. Collectively, the results and analysis provide fundamental insights concerning the molecular design of PDT agents. C1 [Yang, Eunkyung; Holten, Dewey] Washington Univ, Dept Chem, St Louis, MO 63130 USA. [Diers, James R.; Bocian, David F.] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lindsey, Jonathan S.] N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. RP Lindsey, JS (reprint author), N Carolina State Univ, Dept Chem, Box 8204, Raleigh, NC 27695 USA. EM jlindsey@ncsu.edu; David.Bocian@ucr.edu; holten@wustl.edu RI Lindsey, Jonathan/J-7761-2012; Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; JimmyV NCSU Cancer Therapeutics Training Program; National Institute of Allergy and Infectious Diseases [R41AI072854]; Division of Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences of the U.S. Department of Energy [DE-FG02-05ER15660, DE-FG02-05ER15661] FX This work was supported by grants from the NIH (R01AI050875 to M. R. H.), and the JimmyV NCSU Cancer Therapeutics Training Program. Y.-Y.H. was supported by a grant (R41AI072854) from the National Institute of Allergy and Infectious Diseases to NIRvana Pharmaceuticals, Inc. Characterization of the photophysical, redox and molecular-orbital properties of the bacteriochlorins described herein were initially motivated by solar energy studies and supported by grants from the Division of Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences of the U.S. Department of Energy to D.F.B. (DE-FG02-05ER15660) and D.H. (DE-FG02-05ER15661). NR 37 TC 24 Z9 25 U1 3 U2 40 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2013 VL 89 IS 3 BP 605 EP 618 DI 10.1111/php.12021 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 134RU UT WOS:000318232800010 PM 23163632 ER PT J AU Tanaka, M Mroz, P Dai, TH Huang, LY Morimoto, Y Kinoshita, M Yoshihara, Y Shinomiya, N Seki, S Nemoto, K Hamblin, MR AF Tanaka, Masamitsu Mroz, Pawel Dai, Tianhong Huang, Liyi Morimoto, Yuji Kinoshita, Manabu Yoshihara, Yasuo Shinomiya, Nariyoshi Seki, Shuhji Nemoto, Koichi Hamblin, Michael R. TI Linezolid and Vancomycin Decrease the Therapeutic Effect of Methylene Blue-Photodynamic therapy in a Mouse Model of MRSA Bacterial Arthritis SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; WOUND INFECTIONS; IN-VIVO; MICE; NEUTROPHILS AB We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In this study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time noninvasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, whereas LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P<0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT. C1 [Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Huang, Liyi; Hamblin, Michael R.] Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02115 USA. [Tanaka, Masamitsu; Yoshihara, Yasuo; Nemoto, Koichi] Natl Def Med Coll, Dept Orthoped Surg, Tokorozawa, Saitama 3598513, Japan. [Tanaka, Masamitsu; Morimoto, Yuji; Shinomiya, Nariyoshi] Natl Def Med Coll, Dept Integrated Physiol & Bionano Med, Tokorozawa, Saitama 3598513, Japan. [Kinoshita, Manabu; Seki, Shuhji] Natl Def Med Coll, Dept Immunol & Microbiol, Tokorozawa, Saitama 3598513, Japan. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Morimoto, Y (reprint author), Natl Def Med Coll, Dept Integrated Physiol & Bionano Med, Tokorozawa, Saitama 3598513, Japan. EM moyan@ndmc.ac.jp; ham-blin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [23659628]; US NIH [R01AI050875]; National Natural Science Foundation of China [81260239]; Airlift Research Foundation [109421] FX This work was supported by a Grant-in-Aid for Challenging Exploratory Research (23659628) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Yuji Morimoto. Michael R. Hamblin was supported by US NIH grant no. R01AI050875, Liyi Huang by National Natural Science Foundation of China (grant no. 81260239) and Tianhong Dai by an Airlift Research Foundation Extremity Trauma Research Grant (grant no. 109421). We would like to thank Hoon Chung MD, PhD (Wellman Center for Photomedicine, Massachusetts General Hospital) for his technical support and advice. NR 23 TC 4 Z9 4 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2013 VL 89 IS 3 BP 679 EP 682 DI 10.1111/php.12040 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 134RU UT WOS:000318232800019 PM 23311407 ER PT J AU Saladi, SV Wong, PG Trivedi, AR Marathe, HG Keenen, B Aras, S Liew, ZQ Setaluri, V de la Serna, IL AF Saladi, Srinivas V. Wong, Philip G. Trivedi, Archit R. Marathe, Himangi G. Keenen, Bridget Aras, Shweta Liew, Zi-Qi Setaluri, Vijayasaradhi de la Serna, Ivana L. TI BRG1 promotes survival of UV-irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE melanoma; MITF; SWI; SNF enzymes; chromatin remodeling; ultraviolet radiation; apoptosis; ML-IAP ID CHROMATIN REMODELING COMPLEXES; TRANSCRIPTION FACTOR; ULTRAVIOLET-RADIATION; MALIGNANT-MELANOMA; SWI/SNF COMPLEXES; LINEAGE SURVIVAL; BREAST-CANCER; ML-IAP; PROTEIN; EXPRESSION AB Microphthalmia-associated transcription factor (MITF) is a survival factor in melanocytes and melanoma cells. MITF regulates expression of antiapoptotic genes and promotes lineage-specific survival in response to ultraviolet (UV) radiation and to chemotherapeutics. SWI/SNF chromatin-remodeling enzymes interact with MITF to regulate MITF target gene expression. We determined that the catalytic subunit, BRG1, of the SWI/SNF complex protects melanoma cells against UV-induced death. BRG1 prevents apoptosis in UV-irradiated melanoma cells by activating expression of the melanoma inhibitor of apoptosis (ML-IAP). Down-regulation of ML-IAP compromises BRG1-mediated survival of melanoma cells in response to UV radiation. BRG1 regulates ML-IAP expression by cooperating with MITF to promote transcriptionally permissive chromatin structure on the ML-IAP promoter. The alternative catalytic subunit, BRM, and the BRG1-associated factor, BAF180, were found to be dispensable for elevated expression of ML-IAP in melanoma cells. Thus, we illuminate a lineage-specific mechanism by which a specific SWI/SNF subunit, BRG1, modulates the cellular response to DNA damage by regulating an antiapoptotic gene and implicate this subunit of the SWI/SNF complex in mediating the prosurvival function of MITF. C1 [Saladi, Srinivas V.; Wong, Philip G.; Trivedi, Archit R.; Marathe, Himangi G.; Keenen, Bridget; Aras, Shweta; Liew, Zi-Qi; de la Serna, Ivana L.] Univ Toledo, Coll Med, Dept Biochem & Canc Biol, Toledo, OH 43606 USA. [Setaluri, Vijayasaradhi] Univ Wisconsin, Dept Dermatol, Madison, WI USA. RP de la Serna, IL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, 55 Fruit St, Boston, MA 02114 USA. EM ivana.delaserna@utoledo.edu FU National Institute of Health [R01 (ARO59379)] FX ILD was supported by National Institute of Health R01 (ARO59379). NR 45 TC 11 Z9 11 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD MAY PY 2013 VL 26 IS 3 BP 377 EP 391 DI 10.1111/pcmr.12088 PG 15 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 133CD UT WOS:000318114100017 PM 23480510 ER PT J AU Webber, JT Askenazi, M Ficarro, SB Iglehart, MA Marto, JA AF Webber, James T. Askenazi, Manor Ficarro, Scott B. Iglehart, Max A. Marto, Jarrod A. TI Library dependent LC-MS/MS acquisition via mzAPI/Live SO PROTEOMICS LA English DT Article DE LC-MS; Mass informatics; MS; Quantitative proteomics; Technology ID TRANSFORM MASS-SPECTROMETRY; PEPTIDE; IDENTIFICATION; IONIZATION; PROTEOMICS AB The use of MS for characterization of small molecules, nucleotides, and proteins in model organisms as well as primary tissues and clinical samples continues to proliferate at a rapid pace. The complexity and dynamic range of target analytes in biological systems hinders comprehensive analysis and simultaneously drives improvements in instrument hardware and software. As a result, state-of-the-art commercial mass spectrometers are equipped with sophisticated embedded control systems that provide robust acquisition methods accessed through intuitive graphical interfaces. Although optimized for speed, these preconfigured scan functions are otherwise closed to end-user customization beyond simple, analytical-centric parameters supplied by the manufacturer. Here, we present an open-source framework (mzAPI/Live) that enables users to generate arbitrarily complex LC-MSn acquisition methods via simple Python scripting. As a powerful proof-of-concept, we demonstrate real-time assignment of tandem mass spectra through rapid query of NIST peptide libraries. This represents an unprecedented capability to make acquisition decisions based on knowledge of analyte structures determined during the run itself, thus providing a path toward biology-driven MS data acquisition for the broader community. C1 [Webber, James T.; Askenazi, Manor; Ficarro, Scott B.; Iglehart, Max A.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Webber, James T.; Askenazi, Manor; Ficarro, Scott B.; Iglehart, Max A.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91905 Jerusalem, Israel. [Askenazi, Manor; Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,Smith 1158A, Boston, MA 02215 USA. EM jarrod_marto@dfci.harvard.edu OI Webber, James/0000-0001-8594-9888 FU NINDS NIH HHS [P01 NS047572, P01NS047572] NR 23 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAY PY 2013 VL 13 IS 9 BP 1412 EP 1416 DI 10.1002/pmic.201200583 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 132ED UT WOS:000318049800004 PM 23457059 ER PT J AU Zondervan, RL Hahn, PF Sadow, CA Liu, B Lee, SI AF Zondervan, Robert L. Hahn, Peter F. Sadow, Cheryl A. Liu, Bob Lee, Susanna I. TI Body CT Scanning in Young Adults: Examination Indications, Patient Outcomes, and Risk of Radiation-induced Cancer SO RADIOLOGY LA English DT Article ID ITERATIVE RECONSTRUCTION TECHNIQUE; MINOR HEAD-INJURY; COMPUTED-TOMOGRAPHY; FEMALE BREAST; RADIOLOGY; RULE; MANAGEMENT; PROTOCOLS; EXPOSURE; CRITERIA AB Purpose: To quantify patient outcome and predicted cancer risk from body computed tomography (CT) in young adults and identify common indications for the imaging examination. Materials and Methods: This retrospective multicenter study was HIPAA compliant and approved by the institutional review boards of three institutions, with waiver of informed consent. The Research Patient Data Registry containing patient medical and billing records of three university-affiliated hospitals in a single metropolitan area was queried for patients 18-35 years old with a social security record who underwent chest or abdominopelvic CT from 2003 to 2007. Patients were analyzed according to body part imaged and scanning frequency. Mortality status and follow-up interval were recorded. The Biologic Effects of Ionizing Radiation VII method was used to calculate expected cancer incidence and death. Examination indication was determined with associated ICD-9 diagnostic code; 95% confidence intervals for percentages were calculated, and the binomial test was used to compare the difference between percentages. Results: In 21 945 patients, 16 851 chest and 24 112 abdominopelvic CT scans were obtained. During the average 5.5-year (+/- 0.1 [standard deviation]) follow-up, 7.1% (575 of 8057) of chest CT patients and 3.9% (546 of 13 888) of abdominal CT patients had died. In comparison, the predicted risk of dying from CT-induced cancer was 0.1% (five of 8057, P < .01) and 0.1% (eight of 12 472, P < .01), respectively. The most common examination indications were cancer and trauma for chest CT and abdominal pain, trauma, and cancer for abdominopelvic CT. Among patients without a cancer diagnosis in whom only one or two scans were obtained, mortality and predicted risk of radiation-induced cancer death were 3.6% (215 of 5914) and 0.05% (three of 5914, P < .01) for chest CT and 1.9% (219 of 11 291) and 0.1% (six of 11 291, P < .01) for abdominopelvic CT. Conclusion: Among young adults undergoing body CT, risk of death from underlying morbidity is more than an order of magnitude greater than death from long-term radiation-induced cancer. (C) RSNA, 2013 C1 [Zondervan, Robert L.; Hahn, Peter F.; Liu, Bob; Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Liu, Bob; Lee, Susanna I.] Massachusetts Gen Hosp, Webster Ctr Radiat Res & Educ, Boston, MA 02114 USA. [Sadow, Cheryl A.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Zondervan, RL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM robert.zondervan@gmail.com NR 32 TC 26 Z9 30 U1 1 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2013 VL 267 IS 2 BP 460 EP 469 DI 10.1148/radiol.12121324 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132LM UT WOS:000318069700017 PM 23386731 ER PT J AU Cohen, SP Bicket, MC Jamison, D Wilkinson, I Rathmell, JP AF Cohen, Steven P. Bicket, Mark C. Jamison, David Wilkinson, Indy Rathmell, James P. TI Epidural Steroids A Comprehensive, Evidence-Based Review SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Review ID LOW-BACK-PAIN; LUMBAR DISC HERNIATION; RANDOMIZED CONTROLLED-TRIAL; 2000-2010 TASK-FORCE; ACTIVE CONTROL TRIAL; CERVICAL TRANSFORAMINAL INJECTION; POSTDURAL PUNCTURE HEADACHE; CENTRAL SPINAL STENOSIS; NERVE ROOT COMPRESSION; CONTRAST FLOW PATTERNS AB Epidural steroid injections (ESIs) are the most widely utilized pain management procedure in the world, their use supported by more than 45 placebo-controlled studies and dozens of systematic reviews. Despite the extensive literature on the subject, there continues to be considerable controversy surrounding their safety and efficacy. The results of clinical trials and review articles are heavily influenced by specialty, with those done by interventional pain physicians more likely to yield positive findings. Overall, more than half of controlled studies have demonstrated positive findings, suggesting a modest effect size lasting less than 3 months in well-selected individuals. Transforaminal injections are more likely to yield positive results than interlaminar or caudal injections, and subgroup analyses indicate a slightly greater likelihood for a positive response for lumbar herniated disk, compared with spinal stenosis or axial spinal pain. Other factors that may increase the likelihood of a positive outcome in clinical trials include the use of a nonepidural (eg, intramuscular) control group, higher volumes in the treatment group, and the use of depo-steroid. Serious complications are rare following ESIs, provided proper precautions are taken. Although there are no clinical trials comparing different numbers of injections, guidelines suggest that the number of injections should be tailored to individual response, rather than a set series. Most subgroup analyses of controlled studies show no difference in surgical rates between ESI and control patients; however, randomized studies conducted by spine surgeons, in surgically amenable patients with standardized operative criteria, indicate that in some patients the strategic use of ESI may prevent surgery. (Reg Anesth Pain Med 2013; 38: 175-200) C1 [Cohen, Steven P.; Bicket, Mark C.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Cohen, Steven P.; Jamison, David] Walter Reed Natl Mil Med Ctr, Dept Anesthesiol, Pain Management Ctr, Bethesda, MD USA. [Wilkinson, Indy] Womack Army Med Ctr, Dept Anesthesiol, Ft Bragg, NC USA. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr, Boston, MA USA. RP Cohen, SP (reprint author), 550 North Broadway,Suite 301, Baltimore, MD 21029 USA. EM scohen40@jhmi.edu FU Center for Rehabilitation Sciences Research, US Army FX This work was funded in part by the Center for Rehabilitation Sciences Research, US Army (to S.P.C.). NR 316 TC 81 Z9 83 U1 7 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2013 VL 38 IS 3 BP 175 EP 200 DI 10.1097/AAP.0b013e31828ea086 PG 26 WC Anesthesiology SC Anesthesiology GA 131BQ UT WOS:000317966200003 PM 23598728 ER PT J AU Bastu, E Yeh, J AF Bastu, Ercan Yeh, John TI Nature of Light: Spectroscopic Techniques in Obstetrics and Gynecology Applications SO REPRODUCTIVE SCIENCES LA English DT Review DE spectroscopy; obstetrics; gynecology; diagnosis; non-invasive ID NEAR-INFRARED SPECTROSCOPY; MAGNETIC-RESONANCE-SPECTROSCOPY; NONINVASIVE EMBRYO ASSESSMENT; SERUM PROTEOMIC FEATURES; OVARIAN-CANCER; UTERINE CERVIX; IN-VIVO; WOMEN; TISSUE; BIOMARKERS AB In recent years, advances in spectroscopic techniques led to an increase in their medical applications. In medical sciences, emphasis is increasingly placed on instrumental techniques and accurate, quantitative measurements. It is especially apparent in diagnosis, where imaging techniques and laboratory results have became invaluable and compulsory. Breakthroughs in biochemistry made it possible to characterize physiological processes and living organisms at the molecular level. This led to a proliferation of new methods such as DNA tests and the use of biomarkers in daily clinical practice. Characterization of molecular structure and determination of the composition of a mixture are the fields of analytical chemistry and analytical biochemistry. C1 [Bastu, Ercan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Bastu, Ercan] Istanbul Univ, Sch Med, Dept Obstet & Gynecol, Istanbul, Turkey. [Yeh, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Yeh, J (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM jyeh@partners.org NR 42 TC 1 Z9 1 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAY PY 2013 VL 20 IS 5 BP 500 EP 513 DI 10.1177/1933719112446071 PG 14 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 131KF UT WOS:000317991200002 PM 22581802 ER PT J AU Woods, DC White, YAR Niikura, Y Kiatpongsan, S Lee, HJ Tilly, JL AF Woods, Dori C. White, Yvonne A. R. Niikura, Yuichi Kiatpongsan, Sorapop Lee, Ho-Joon Tilly, Jonathan L. TI Embryonic Stem Cell-Derived Granulosa Cells Participate in Ovarian Follicle Formation In Vitro and In Vivo SO REPRODUCTIVE SCIENCES LA English DT Article DE granulosa cells; Foxl2; embryonic stem cell; oocyte; follicle; ovary ID TRANSCRIPTION FACTOR; GERM-CELLS; MOUSE; OOCYTES; EXPRESSION; DERIVATION; PROGRESS; DIRECTS; GENES; MICE AB Differentiating embryonic stem cells (ESCs) can form ovarian follicle-like structures in vitro, consisting of an oocyte-like cell surrounded by somatic cells capable of steroidogenesis. Using a dual-fluorescence reporter system in which mouse ESCs express green fluorescent protein (GFP) under the control of a germ cell-specific Pou5f1 gene promoter and red fluorescent protein (Discosoma sp red [DsRed]) driven by the granulosa cell-specific Forkhead box L2 (Foxl2) gene promoter, we first confirmed in vitro formation of follicle-like structures containing GFP-positive cells surrounded by DsRed-positive cells. Isolated DsRed-positive cells specified from ECSs exhibited a gene expression profile consistent with granulosa cells, as revealed by the detection of messenger RNAs (mRNAs) for Foxl2, follistatin (Fst), anti-Mullerian hormone (Amh), and follicle-stimulating hormone receptor (Fshr) as well as by production of both progesterone and estradiol. In addition, treatment of isolated DsRed-expressing cells with follicle-stimulating hormone (FSH) significantly increased estradiol production over basal levels, confirming the presence of functional FSH receptors in these cells. Last, ESC-derived DsRed-positive cells injected into neonatal mouse ovaries became incorporated within the granulosa cell layer of immature follicles. These studies demonstrate that Foxl2-expressing ovarian somatic cells derived in vitro from differentiating ESCs express granulosa cell markers, actively associate with germ cells in vitro, synthesize steroids, respond to FSH, and participate in folliculogenesis in vivo. C1 [Woods, Dori C.; White, Yvonne A. R.; Niikura, Yuichi; Kiatpongsan, Sorapop; Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, MGH Vincent Dept Obstet & Gynecol,Med Sch, Boston, MA USA. [Woods, Dori C.; White, Yvonne A. R.; Niikura, Yuichi; Kiatpongsan, Sorapop; Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, THR 901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU United States Department of Agriculture National Research Initiative Competitive Grant [2007-35203-18085]; Ruth L. Kirschstein National Research Service Award [NIH F32-AG034809]; National Institute on Aging [NIH R37-AG012279]; Glenn Foundation for Research in the Biological Mechanisms of Aging FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a United States Department of Agriculture National Research Initiative Competitive Grant (2007-35203-18085 to D. C. W.), a Ruth L. Kirschstein National Research Service Award (NIH F32-AG034809 to D. C. W.), a Method to Extend Research in Time (MERIT) Award from the National Institute on Aging (NIH R37-AG012279 to J.L.T.), and a grant from the Glenn Foundation for Research in the Biological Mechanisms of Aging (to J.L.T.). NR 24 TC 9 Z9 10 U1 3 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAY PY 2013 VL 20 IS 5 BP 524 EP 535 DI 10.1177/1933719113483017 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 131KF UT WOS:000317991200004 PM 23536570 ER PT J AU Ginat, DT Singh, AD Moonis, G AF Ginat, Daniel T. Singh, Arun D. Moonis, Gul TI Untitled Reply SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Letter C1 [Ginat, Daniel T.; Moonis, Gul] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ginat, Daniel T.; Moonis, Gul] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Singh, Arun D.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA. RP Ginat, DT (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAY PY 2013 VL 33 IS 5 BP 1090 EP 1090 DI 10.1097/IAE.0b013e318281b992 PG 1 WC Ophthalmology SC Ophthalmology GA 131QY UT WOS:000318011100033 PM 23549093 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Medical and psychological comorbidity predicts poor pain outcomes after total knee arthroplasty SO RHEUMATOLOGY LA English DT Article DE pain; function; functional limitation; total knee replacement; primary; arthroplasty; joint replacement; outcomes; patient-reported outcomes ID TOTAL HIP-ARTHROPLASTY; UNITED-STATES; REVISION HIP; REPLACEMENT; AGE; LIMITATION; MORBIDITY; IMPACT; INDEX; TKA AB Objective. To study comorbidity correlates of moderate to severe pain after total knee arthroplasty (TKA). Methods. We analysed prospectively collected Total Joint Registry data to examine whether medical (heart disease, peripheral vascular disease, renal disease, chronic obstructive pulmonary disease, diabetes and CTD) and psychological (anxiety and depression) comorbidity is associated with moderate to severe pain after primary or revision TKA. Multivariable-adjusted logistic regression simultaneously adjusted for all comorbidities, age, sex, BMI, underlying diagnosis, American Society of Anesthesiologist (ASA) class, distance from medical centre and implant fixation (only for primary TKA) was used to analyse primary and revision TKA separately. Results. The primary TKA cohort consisted of 7139 and 4234 TKAs (response rates 65% and 57%) and the revision TKA cohort consisted of 1533 and 881 TKAs at 2 and 5 years (response rates 57% and 48%), respectively. In the primary TKA cohort, anxiety was associated with 1.4 higher odds (95% CI 1.0, 2.0) of moderate to severe index knee pain at 2 years; at 5 years, heart disease (OR 1.7; 95% CI 1.1, 2.6), depression (OR 1.7; 95% CI 1.1, 2.5) and anxiety (OR 1.9; 95% CI 1.2, 3.1) were significantly associated with moderate to severe pain. For revision TKA, CTD (OR 0.5; 95% CI 0.2, 0.9) and depression (OR 1.8; 95% CI 1.1, 3.1) were significantly associated with moderate to severe pain. Conclusion. This study identified medical and psychological comorbidity risk factors for moderate to severe pain after primary and revision TKA. This information can be used to provide realistic outcome expectations for patients before undergoing primary or revision TKA. C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Agency for Health Quality and the Research Center for Education and Research on Therapeutics (CERTs); Mayo Clinic; National Institutes of Health (NIH) (Mayo Clinic Center for Clinical and Translational Research) [1 KL2 RR024151-01]; DePuy; Stryker; Biomet; Zimmer; Takeda; Savient; URL Pharmaceuticals; Ardea; Allergan; Regeneron; Novartis; National Institute of Aging; National Cancer Institute; Pipeline Biomedical FX The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. J.A.S. is supported by grants from the Agency for Health Quality and the Research Center for Education and Research on Therapeutics (CERTs), the National Institute of Aging and the National Cancer Institute.; This material is the result of work supported with research grants from Mayo Clinic Orthopedic Surgery research funds, National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL, USA.; D.G.L. has received royalties from Zimmer, has been a paid consultant and owns stock in Pipeline Biomedical and his institution has received research funds from DePuy, Stryker, Biomet and Zimmer. J.A.S. has received research and travel grants from Takeda and Savient and consultant fees from URL Pharmaceuticals, Savient, Takeda, Ardea, Allergan, Regeneron and Novartis. NR 36 TC 39 Z9 40 U1 2 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD MAY PY 2013 VL 52 IS 5 BP 916 EP 923 DI 10.1093/rheumatology/kes402 PG 8 WC Rheumatology SC Rheumatology GA 133CG UT WOS:000318114400025 PM 23325037 ER PT J AU Ventura, J Reise, SP Keefe, RSE Hurford, IM Wood, RC Bilder, RM AF Ventura, Joseph Reise, Steven P. Keefe, Richard S. E. Hurford, Irene M. Wood, Rachel C. Bilder, Robert M. TI The Cognitive Assessment Interview (CAI): Reliability and Validity of a Brief Interview-Based Measure of Cognition SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; functional outcome; functional capacity; symptoms; informant ratings; neurocognition ID PSYCHIATRIC RATING-SCALE; FUNCTIONAL-CAPACITY; QUALITY-ASSURANCE; SCHIZOPHRENIA; PERFORMANCE; IMPAIRMENT; VALIDATION; PREDICTION; SYMPTOMS; SELF AB Objective: To obtain Food and Drug Administration approval for the treatment of cognitive impairments associated with schizophrenia, a drug will need to demonstrate benefits beyond those that may be documented on objective cognitive tests. Interview-based measures of cognition such as the Cognitive Assessment Interview (CAI) are candidate coprimary outcome measures. Methods: Psychiatrically stable schizophrenia outpatients (n = 150) were studied using the CM to obtain information about cognitive functioning from both the patient and an informant. Patients also received objective assessments of neurocognition, functional capacity, functional outcome, and symptoms, at baseline and 1 month later. Results: The CAI had good internal consistency (Cronbach's alpha = .92) and good test-retest reliability (r = .83). The CM was moderately correlated with objective neurocognitive test scores (r's = .39 to -.41) and moderately correlated with social functioning (r = -.38), work functioning (r = -.48), and overall functional outcome (r = -.49). The correlations of CAI scores with external validity indicators did not differ significantly by source of information (patient alone ratings were valid). Overall functional outcome correlated more strongly with patient CM scores (r = -.50) than with objective neurocognitive test scores (r = .29) or functional capacity (r = .29). Conclusions: Field testing of the CM produced reliable ratings of cognitive functioning that were correlated with functional outcome. Patient ratings alone yielded scores with reliability and validity values appropriate for use in clinical trials. The CM appears to provide useful complementary information and possesses practical advantages for rating cognitive functioning including an interview-based method of administration, brief assessment time (15 min for the patient assessment), little or no practice effects, and ease of scoring. C1 [Ventura, Joseph; Wood, Rachel C.; Bilder, Robert M.] Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Reise, Steven P.; Bilder, Robert M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Keefe, Richard S. E.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Hurford, Irene M.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Hurford, Irene M.] Philadelphia Vet Affairs Med Ctr, Dept Behav Hlth, Philadelphia, PA USA. RP Ventura, J (reprint author), Univ Calif Los Angeles, Dept Psychiat, 300 Med Plaza,Room 2243, Los Angeles, CA 90095 USA. EM jventura@ucla.edu RI Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 FU Pfizer, Inc.; National Institute of Mental Health (NIMH) [1R21MH073971, MH37705, P50 MH066286]; Consortium for Neuropsychiatric Phonemics [UL1-DE019580, RL1LM009833] FX This research was supported by an investigator initiated grant from Pfizer, Inc. and from an National Institute of Mental Health (NIMH) grant 1R21MH073971 that were awarded to J.V., PhD. This research was also supported in part by NIMH Grants MH37705 (P.I.: Keith H. Nuechterlein, PhD), P50 MH066286 (P.I.: Keith H. Nuechterlein, PhD), and the Consortium for Neuropsychiatric Phonemics UL1-DE019580, RL1LM009833 (PI: R.M.B., PhD). NR 39 TC 14 Z9 14 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2013 VL 39 IS 3 BP 583 EP 591 DI 10.1093/schbul/sbs001 PG 9 WC Psychiatry SC Psychiatry GA 133IN UT WOS:000318132200018 PM 22328641 ER PT J AU Harvey, PO Zaki, J Lee, J Ochsner, K Green, MF AF Harvey, Philippe-Olivier Zaki, Jamil Lee, Junghee Ochsner, Kevin Green, Michael F. TI Neural Substrates of Empathic Accuracy in People With Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE social cognition; empathic accuracy; emotional expressivity; schizophrenia; functional imaging ID SOCIAL COGNITION; MAJOR DEPRESSION; BASES; MIND; ATTRIBUTION; PERCEPTION; EMOTION; EXPRESSIVITY; CIRCUITRY; FEELINGS AB Introduction: Empathic deficits in schizophrenia may lead to social dysfunction, but previous studies of schizophrenia have not modeled empathy through paradigms that (1) present participants with naturalistic social stimuli and (2) link brain activity to "accuracy" about inferring other's emotional states. This study addressed this gap by investigating the neural correlates of empathic accuracy (EA) in schizophrenia. Methods: Fifteen schizophrenia patients and 15 controls were scanned while continuously rating the affective state of another person shown in a series of videos (ie, targets). These ratings were compared with targets' own self-rated affect, and EA was defined as the correlation between participants' ratings and targets' self-ratings. Targets' self-reported emotional expressivity also was measured. We searched for brain regions whose activity tracked parametrically with (1) perceivers' EA and (2) targets' expressivity. Results: Patients showed reduced EA compared with controls. The left precuneus, left middle frontal gyms, and bilateral thalamus were significantly more correlated with EA in controls compared with patients. High expressivity in targets was associated with better EA in controls but not in patients. High expressivity was associated with increased brain activity in a large set of regions in controls (eg, fusiform gyrus, medial prefrontal cortex) but not in patients. Discussion: These results use a naturalistic performance measure to confirm that schizophrenic patients demonstrate impaired ability to understand others' internal states. They provide novel evidence about a potential mechanism for this impairment: schizophrenic patients failed to capitalize on targets' emotional expressivity and also demonstrate reduced neural sensitivity to targets' affective cues. C1 [Harvey, Philippe-Olivier] Douglas Mental Hlth Univ Inst, Montreal, PQ H4H 1R3, Canada. [Zaki, Jamil] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Lee, Junghee; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Lee, Junghee; Green, Michael F.] Healthcare Ctr Syst, VA Greater Los Angeles, Los Angeles, CA USA. [Ochsner, Kevin] Columbia Univ, Dept Psychol, New York, NY 10027 USA. RP Harvey, PO (reprint author), Douglas Mental Hlth Univ Inst, 6875 LaSalle Blvd, Montreal, PQ H4H 1R3, Canada. EM philippe-olivier.harvey@douglas.mcgill.ca RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU Desert Pacific Mental Illness Research, Education, and Clinical Center; UCLA Brain Mapping Center; Canadian Institutes of Health Research; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer Jones-Simon; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund; [MH043292] FX This work was supported by pilot grants from the Desert Pacific Mental Illness Research, Education, and Clinical Center and the UCLA Brain Mapping Center. This work was also supported by grant MH043292 to Dr M.F.G. Poorang Nori assisted in data collection. Dr P.O.H. is supported by a postdoctoral fellowship from the Canadian Institutes of Health Research.; For generous support of the UCLA Brain Mapping Center, we also thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon, Capital Group Companies Charitable Foundation, Robson Family, and Northstar Fund. Financial Disclosures: The authors have no financial disclosure to report. The authors have declared that there are no conflicts of interest in relation to the subject of this study. NR 56 TC 19 Z9 19 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2013 VL 39 IS 3 BP 617 EP 628 DI 10.1093/schbul/sbs042 PG 12 WC Psychiatry SC Psychiatry GA 133IN UT WOS:000318132200022 PM 22451493 ER PT J AU Lee, J Kern, RS Harvey, PO Horan, WP Kee, KS Ochsner, K Penn, DL Green, MF AF Lee, Junghee Kern, Robert S. Harvey, Philippe-Olivier Horan, William P. Kee, Kimmy S. Ochsner, Kevin Penn, David L. Green, Michael F. TI An Intact Social Cognitive Process in Schizophrenia: Situational Context Effects on Perception of Facial Affect SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; contextual modulation; facial affect processing; social cognition ID PREFRONTAL CORTEX; SURPRISED FACES; EMOTION; EXPRESSIONS; TASK; ORGANIZATION; SPECTRUM; AMYGDALA; FMRI AB Background: Impaired facial affect recognition is the most consistent social cognitive finding in schizophrenia. Although social situations provide powerful constraints on our perception, little is known about how situational context modulates facial affect recognition in schizophrenia. Methods: Study 1 was a single-site study with 34 schizophrenia patients and 22 healthy controls. Study 2 was a 2-site study with 68 schizophrenia patients and 28 controls. Both studies administered a Situational Context Facial Affect Recognition Task with 2 conditions: a situational context condition and a no-context condition. For the situational context condition, a briefly shown face was preceded by a sentence describing either a fear- or surprise-inducing event. In the no-context condition, a face was presented without a sentence. For both conditions, subjects rated how fearful or surprised the face appeared on a 9-point Likert scale. Results: For the situational context condition of study 1, both patients and controls rated faces as more afraid when they were paired with fear-inducing sentences and as more surprised when they were paired with surprise-inducing sentences. The degree of modulation was comparable across groups. For the no-context condition, patients rated faces comparably to controls. The findings of study 2 replicated those from study 1. Conclusions: Despite previous abnormalities in other types of context paradigms, this study found intact situational context processing in schizophrenia, suggesting that patients benefit from situational context when interpreting ambiguous facial expression. This area of relative social cognitive strength in schizophrenia has implications for social cognitive training programs. C1 [Lee, Junghee; Kern, Robert S.; Harvey, Philippe-Olivier; Horan, William P.; Kee, Kimmy S.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Lee, Junghee; Kern, Robert S.; Harvey, Philippe-Olivier; Horan, William P.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. [Harvey, Philippe-Olivier] McGill Univ, Douglas Mental Heath Univ Inst, Montreal, PQ, Canada. [Kee, Kimmy S.] Calif State Univ, Dept Psychol, Camarillo, CA USA. [Ochsner, Kevin] Columbia Univ, Dept Psychol, New York, NY 10027 USA. [Penn, David L.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. RP Lee, J (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 300 Med Plaza Room 2261, Los Angeles, CA 90095 USA. EM jungheelee@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institutes of Mental Health [MH043292, MH087618] FX National Institutes of Mental Health (MH043292 and MH087618 to PI: M.F.G., PhD). NR 36 TC 11 Z9 11 U1 4 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2013 VL 39 IS 3 BP 640 EP 647 DI 10.1093/schbul/sbs063 PG 8 WC Psychiatry SC Psychiatry GA 133IN UT WOS:000318132200024 PM 22532704 ER PT J AU Mueser, KT Glynn, SM Cather, C Xie, HY Zarate, R Smith, LF Clark, RE Gottlieb, JD Wolfe, R Feldman, J AF Mueser, Kim T. Glynn, Shirley M. Cather, Corrine Xie, Haiyi Zarate, Roberto Smith, Lindy Fox Clark, Robin E. Gottlieb, Jennifer D. Wolfe, Rosemarie Feldman, James TI A Randomized Controlled Trial of Family Intervention for Co-occurring Substance Use and Severe Psychiatric Disorders SO SCHIZOPHRENIA BULLETIN LA English DT Article DE dual disorders; dual diagnosis; family psychoeducation; family therapy ID SEVERE MENTAL-ILLNESS; COGNITIVE-BEHAVIORAL THERAPY; DRUG-USE; MOTIVATIONAL INTERVENTION; INTEGRATED TREATMENT; POWER CALCULATIONS; ABUSE DISORDERS; CLINICAL-TRIAL; SCHIZOPHRENIA; PEOPLE AB Substance use disorders have a profound impact on the course of severe mental illnesses and on the family, but little research has evaluated the impact of family intervention for this population. To address this question, a randomized controlled trial was conducted comparing a brief (2-3 mo) Family Education (ED) program with a longer-term (9-18 mo) program that combined education with teaching communication and problem-solving skills, Family Intervention for Dual Disorders (FIDD). A total of 108 clients (77% schizophrenia-spectrum) and a key relative were randomized to either ED or FIDD and assessed at baseline and every 6 months for 3 years. Rates of retention of families in both programs were moderate. Intent-to-treat analyses indicated that clients in both programs improved in psychiatric, substance abuse, and functional outcomes, as did key relatives in knowledge of co-occurring disorders, burden, and mental health functioning. Clients in FIDD had significantly less severe overall psychiatric symptoms and psychotic symptoms and tended to improve more in functioning. Relatives in FIDD improved more in mental health functioning and knowledge of co-occurring disorders. There were no consistent differences between the programs in substance abuse severity or family burden. The findings support the utility of family intervention for co-occurring disorders, and the added benefits of communication and problem-solving training, but also suggest the need to modify these programs to retain more families in treatment in order to provide them with the information and skills they need to overcome the effects of these disorders. C1 [Mueser, Kim T.; Gottlieb, Jennifer D.] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. [Mueser, Kim T.; Gottlieb, Jennifer D.] Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. [Glynn, Shirley M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Glynn, Shirley M.; Zarate, Roberto] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Cather, Corrine] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Cather, Corrine; Feldman, James] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Xie, Haiyi; Smith, Lindy Fox; Wolfe, Rosemarie] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. [Xie, Haiyi; Smith, Lindy Fox; Wolfe, Rosemarie] Dartmouth Psychiat Res Ctr, Concord, NH USA. [Zarate, Roberto] Pacific Clin, Los Angeles, CA USA. [Clark, Robin E.] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, Shrewsbury, MA USA. [Feldman, James] Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Mueser, KT (reprint author), Boston Univ, Ctr Psychiat Rehabil, 940 Commonwealth Ave, Boston, MA 02215 USA. EM mueser@bu.edu FU National Institute of Mental Health; National Institute on Drug Abuse [MH62629] FX National Institute of Mental Health; National Institute on Drug Abuse (MH62629). NR 73 TC 13 Z9 13 U1 6 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2013 VL 39 IS 3 BP 658 EP 672 DI 10.1093/schbul/sbr203 PG 15 WC Psychiatry SC Psychiatry GA 133IN UT WOS:000318132200026 PM 22282453 ER PT J AU Walton, E Turner, J Gollub, RL Manoach, DS Yendiki, A Ho, BC Sponheim, SR Calhoun, VD Ehrlich, S AF Walton, Esther Turner, Jessica Gollub, Randy L. Manoach, Dara S. Yendiki, Anastasia Ho, Beng-Choon Sponheim, Scott R. Calhoun, Vince D. Ehrlich, Stefan TI Cumulative Genetic Risk and Prefrontal Activity in Patients With Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; DLPFC; working memory; intermediate phenotype; fMRI; genetic risk score ID VAL(108/158) MET GENOTYPE; WORKING-MEMORY TASK; CORTICAL FUNCTION; FMRI SIGNAL; COMT; CORTEX; ASSOCIATION; ACTIVATION; GENOME; METAANALYSIS AB The lack of consistency of genetic associations in highly heritable mental illnesses, such as schizophrenia, remains a challenge in molecular psychiatry. Because clinical phenotypes for psychiatric disorders are often ill defined, considerable effort has been made to relate genetic polymorphisms to underlying physiological aspects of schizophrenia (so called intermediate phenotypes), that may be more reliable. Given the polygenic etiology of schizophrenia, the aim of this work was to form a measure of cumulative genetic risk and study its effect on neural activity during working memory (WM) using functional magnetic resonance imaging. Neural activity during the Sternberg Item Recognition Paradigm was measured in 79 schizophrenia patients and 99 healthy controls. Participants were genotyped, and a genetic risk score (GRS), which combined the additive effects of 41 single-nucleotide polymorphism (SNPs) from 34 risk genes for schizophrenia, was calculated. These risk SNPs were chosen according to the continuously updated meta-analysis of genetic studies on schizophrenia available at www.schizophreniaresearchforum.org. We found a positive relationship between GRS and left dorsolateral prefrontal cortex inefficiency during WM processing. GRS was not correlated with age, performance, intelligence, or medication effects and did not differ between acquisition sites, gender, or diagnostic groups. Our study suggests that cumulative genetic risk, combining the impact of many genes with small effects, is associated with a known brain-based intermediate phenotype for schizophrenia. The GRS approach could provide an advantage over studying single genes in studies focusing on the genetic basis of polygenic conditions such as neuropsychiatric disorders. C1 [Walton, Esther; Gollub, Randy L.; Manoach, Dara S.; Yendiki, Anastasia; Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Walton, Esther; Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, D-01307 Dresden, Germany. [Turner, Jessica; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Gollub, Randy L.; Manoach, Dara S.; Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Sponheim, Scott R.] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, Fetscherstr 74, D-01307 Dresden, Germany. EM stefan@nmr.mgh.harvard.edu RI Calhoun, Vince/H-7146-2013; Ho, Beng-Choon/D-6959-2011; Turner, Jessica/H-7282-2015; OI Calhoun, Vince/0000-0001-9058-0747; Ho, Beng-Choon/0000-0003-3976-1555; Turner, Jessica/0000-0003-0076-8434; Ehrlich, Stefan/0000-0003-2132-4445; Walton, Esther/0000-0002-0935-2200; Gollub, Randy L./0000-0002-9434-4044 FU National Institutes of Health/National Center for Research Resources [NIH/NCRR P41RR14075]; Department of Energy [DE-FG02-99ER62764]; Mind Research Network, Morphometry BIRN [1U24, RR021382A]; Function Biomedical Informatics Research Network [U24RR021992-01, NIH/NCRR MO1 RR025758-01]; National Institute of Mental Health [1RC1MH089257]; Deutsche Forschungsgemeinschaft; Deutscher Akademischer Auslandsdienst; Friedrich-Ebert Stiftung FX National Institutes of Health/National Center for Research Resources (NIH/NCRR P41RR14075); Department of Energy (DE-FG02-99ER62764); Mind Research Network, Morphometry BIRN (1U24, RR021382A); Function Biomedical Informatics Research Network (U24RR021992-01, NIH/NCRR MO1 RR025758-01, National Institute of Mental Health 1RC1MH089257 to V.D.C.); the Deutsche Forschungsgemeinschaft (Research Fellowship to S.E.); the Deutscher Akademischer Auslandsdienst; and the Friedrich-Ebert Stiftung (stipends to E.W.). NR 43 TC 27 Z9 27 U1 1 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2013 VL 39 IS 3 BP 703 EP 711 DI 10.1093/schbul/sbr190 PG 9 WC Psychiatry SC Psychiatry GA 133IN UT WOS:000318132200030 PM 22267534 ER PT J AU Shinoda, G De Soysa, TY Seligson, MT Yabuuchi, A Fujiwara, Y Huang, PY Hagan, JP Gregory, RI Moss, EG Daley, GQ AF Shinoda, Gen De Soysa, T. Yvanka Seligson, Marc T. Yabuuchi, Akiko Fujiwara, Yuko Huang, Pei Yi Hagan, John P. Gregory, Richard I. Moss, Eric G. Daley, George Q. TI Lin28a Regulates Germ Cell Pool Size and Fertility SO STEM CELLS LA English DT Article DE Germ cells; Lin28a; miR-let7; Fertility ID GENOME-WIDE ASSOCIATION; MICRORNA; AGE; MENARCHE; LIN-28; ELEGANS; PUBERTY; MOUSE; RNA AB Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males, the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild-type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. STEM CELLS 2013;31:1001-1009 C1 [Shinoda, Gen; De Soysa, T. Yvanka; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Daley, George Q.] Boston Childrens Hosp, Stem Cell Transplantat Program, Stem Cell Program, Div Pediat Hematol Oncol, Boston, MA USA. [Shinoda, Gen; De Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Hagan, John P.; Gregory, Richard I.; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA. [Fujiwara, Yuko; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Huang, Pei Yi] Boston Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA USA. [Hagan, John P.; Gregory, Richard I.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hagan, John P.] Ohio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Moss, Eric G.] Univ Med & Dent New Jersey, Dept Mol Biol, Newark, NJ 07103 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA USA. RP Daley, GQ (reprint author), Childrens Hosp, 1 Blackfan Circle,Karp Bldg,7th Floor, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu OI Hagan, John/0000-0003-0295-4898 FU Alex's Lemonade Stand Foundation; Ellison Medical Foundation; NIDDK (Hematology Center) for Mouse Embryonic Stem ESCs [P30 DK049216-17]; Gene Targeting Core; Eunice Kennedy Shriver NICHD/NIH (SCCPIR) for The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core [U54-HD28934] FX We thank Achia Urbach and Mathew William Lensch for invaluable discussions and advice, Roderick Bronson and the Harvard Medical School Rodent Histopathology Core for mouse tissue pathology, and The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core for hormone measurement. This work was supported by grants from the Alex's Lemonade Stand Foundation, the Ellison Medical Foundation, the NIDDK (Hematology Center Grant P30 DK049216-17) for Mouse Embryonic Stem ESCs and Gene Targeting Core, and the Eunice Kennedy Shriver NICHD/NIH (SCCPIR) Grant U54-HD28934 for The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core. NR 21 TC 16 Z9 16 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 2013 VL 31 IS 5 BP 1001 EP 1009 DI 10.1002/stem.1343 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 131RV UT WOS:000318014100016 PM 23378032 ER PT J AU Park, HJ Hong, M Bronson, RT Israel, MA Frankel, WN Yun, K AF Park, Hee Jung Hong, Mingi Bronson, Roderick T. Israel, Mark A. Frankel, Wayne N. Yun, Kyuson TI Elevated Id2 Expression Results in Precocious Neural Stem Cell Depletion and Abnormal Brain Development SO STEM CELLS LA English DT Article DE Neural stem cells; Id2; Brain tumor; Glioma; Medulloblastoma; Self-renewal; Apoptosis; Seizure; CyclinG1; Rett syndrome ID LOOP-HELIX PROTEINS; CENTRAL-NERVOUS-SYSTEM; SELF-RENEWAL; RETINOBLASTOMA PROTEIN; HUMAN GLIOBLASTOMA; PROGENITOR CELLS; AXONAL GROWTH; DIFFERENTIATION; PROLIFERATION; NEUROGENESIS AB Id2 is a helix-loop-helix transcription factor essential for normal development, and its expression is dysregulated in many human neurological conditions. Although it is speculated that elevated Id2 levels contribute to the pathogenesis of these disorders, it is unknown whether dysregulated Id2 expression is sufficient to perturb normal brain development or function. Here, we show that mice with elevated Id2 expression during embryonic stages develop microcephaly, and that females in particular are prone to generalized tonic-clonic seizures. Analyses of Id2 transgenic brains indicate that Id2 activity is highly cell context specific: elevated Id2 expression in naive neural stem cells (NSCs) in early neuroepithelium induces apoptosis and loss of NSCs and intermediate progenitors. Activation of Id2 in maturing neuroepithelium results in less severe phenotypes and is accompanied by elevation of G1 cyclin expression and p53 target gene expression. In contrast, activation of Id2 in committed intermediate progenitors has no significant phenotype. Functional analysis with Id2-overexpressing and Id2-null NSCs shows that Id2 negatively regulates NSC self-renewal in vivo, in contrast to previous cell culture experiments. Deletion of p53 function from Id2-transgenic brains rescues apoptosis and results in increased incidence of brain tumors. Furthermore, Id2 overexpression normalizes the increased self-renewal of p53-null NSCs, suggesting that Id2 activates and modulates the p53 pathway in NSCs. Together, these data suggest that elevated Id2 expression in embryonic brains can cause deregulated NSC self-renewal, differentiation, and survival that manifest in multiple neurological outcomes in mature brains, including microcephaly, seizures, and brain tumors. STEM CELLS 2013;31:1010-1021 C1 [Park, Hee Jung; Hong, Mingi; Frankel, Wayne N.; Yun, Kyuson] Jackson Lab, Bar Harbor, ME 04609 USA. [Bronson, Roderick T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Israel, Mark A.] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Lebanon, NH USA. RP Yun, K (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM kyuson.yun@jax.org FU NIH [NS031348]; TJL Cancer Center Support grant [CA034196] FX We thank Jesse Hammer and Stephen Sampson for assistance with manuscript preparation; Michaela Petit and Kasima Brown for technical assistance; Barbara Beyer for EEG electrode implantation and recording, Gene Expression services, Computational Sciences, and Imaging Services at JAX for their assistance with the project. We are grateful to Susan Ackerman and Robert Burgess for their comments on the manuscript. This work was supported by an NIH grant to W.N.F. (NS031348) and TJL Cancer Center Support grant CA034196 to K.Y. M. H. is currently affiliated with Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY. NR 52 TC 3 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 2013 VL 31 IS 5 BP 1010 EP 1021 DI 10.1002/stem.1351 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 131RV UT WOS:000318014100017 PM 23390122 ER PT J AU Lau, AY Wong, KSL Lev, M Furie, K Smith, W Kim, AS AF Lau, Alexander Y. Wong, Ka-sing Lawrence Lev, Michael Furie, Karen Smith, Wade Kim, Anthony S. TI Burden of Intracranial Steno-Occlusive Lesions on Initial Computed Tomography Angiography Predicts Poor Outcome in Patients With Acute Stroke SO STROKE LA English DT Article DE intracranial stenosis; prognosis; stroke; transient ischemic attack ID ARTERIAL-STENOSIS; ISCHEMIC-STROKE; ASIAN PATIENTS; RISK-FACTORS; ATHEROSCLEROSIS; DISEASE; ASPIRIN; RACE AB Background and Purpose-Computed tomography angiography is an accurate noninvasive method to diagnose intracranial steno-occlusive disease (ICAD) at initial presentation for stroke. We aimed to identify features of computed tomography angiography associated with unfavorable outcome. Methods-We identified patients with ICAD in the Screening Technology and Outcomes Project in Stroke Study, a prospective imaging-based study of stroke outcomes, in consecutive patients with ischemic stroke or transient ischemic attack (TIA) presenting to 2 academic medical centers. All patients underwent computed tomography angiography, which were graded by 2 neuroradiologists independently. Univariate and multiple logistic regression was used to evaluate predictors of favorable outcome at 6 months, defined as a modified Rankin Scale <= 2. Results-Among 539 patients that met study entry criteria, ICAD was identified in 212 patients (39%); 116 patients (22%) had concurrent extraintracranial lesions, and 66 patients (12%) had multiple sites of ICAD. Patients with ICAD had more severe stroke (median National Institutes of Health Stroke Scale, 9 versus 3; P<0.001), worse outcomes at 6 months (modified Rankin Scale, 0-2; 57% versus 73%; P<0.001), and higher mortality (18% versus 8%; P=0.001). In the multivariate model, age (odds ratio [OR], 0.75 per decade; 95% confidence interval [CI], 0.65-0.87), female sex (OR, 0.49; 95% CI, 0.32-0.73), multiple sites of ICAD (OR, 0.53; 95% CI, 0.29-0.97), complete occlusion (OR, 0.42; 95% CI, 0.25-0.72), and concurrent extraintracranial lesions (OR, 0.51; 95% CI, 0.31-0.84) negatively predicted favorable outcome. Conclusions-Findings of multiple sites of ICAD from computed tomography angiography, concurrent extraintracranial lesions, and complete occlusion are independent predictors of unfavorable outcome at 6 months. (Stroke. 2013;44:1310-1316.) C1 [Lau, Alexander Y.; Smith, Wade; Kim, Anthony S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Lau, Alexander Y.; Wong, Ka-sing Lawrence] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Lev, Michael] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Furie, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Furie, Karen] Rhode Isl Hosp, Dept Neurol, Providence, RI USA. RP Lau, AY (reprint author), Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. EM alexlau@cuhk.edu.hk RI Lau, Alexander/N-2485-2015; Wong, Ka Sing Lawrence/N-3434-2015 OI Lau, Alexander/0000-0002-5933-9290; Wong, Ka Sing Lawrence/0000-0002-2031-9866 FU Department of Health and Human and Human Services, Agency for Healthcare Research and Quality [RO1-HS011392]; Croucher Foundation; Henry Leung Fellowship FX This research was funded by a grant from the Department of Health and Human and Human Services, Agency for Healthcare Research and Quality, grant number RO1-HS011392. Dr Lau is a recipient of Croucher Foundation Fellowship and Henry Leung Fellowship. NR 26 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2013 VL 44 IS 5 BP 1310 EP 1316 DI 10.1161/STROKEAHA.111.672741 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 131WZ UT WOS:000318030000034 PM 23512979 ER PT J AU Messe, SR Pervez, MA Smith, EE Siddique, KA Hellkamp, AS Saver, JL Bhatt, DL Fonarow, GC Peterson, ED Schwamm, LH AF Messe, Steven R. Pervez, Muhammad A. Smith, Eric E. Siddique, Khawaja A. Hellkamp, Anne S. Saver, Jeffrey L. Bhatt, Deepak L. Fonarow, Gregg C. Peterson, Eric D. Schwamm, Lee H. TI Lipid Profile, Lipid-lowering Medications, and Intracerebral Hemorrhage After tPA in Get With The Guidelines-Stroke SO STROKE LA English DT Article DE hemorrhage; lipid-lowering medication; lipids; stroke; tissue plasminogen activator ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; AMERICAN-HEART-ASSOCIATION; PRIOR STATIN USE; INTRAVENOUS THROMBOLYSIS; INTRACRANIAL HEMORRHAGE; CHOLESTEROL LEVELS; SERUM-CHOLESTEROL; RISK; TRANSFORMATION AB Background and Purpose-Symptomatic intracerebral hemorrhage (sICH) after tissue plasminogen activator for acute ischemic stroke is associated with poor outcome. There are conflicting data on sICH risk related to lipid levels and use of lipid-lowering medications. We evaluated whether there are associations between lipid levels, lipid-lowering medications, and sICH in Get With the Guidelines-Stroke. Methods-We identified acute ischemic stroke patients in the Get With the Guidelines-Stroke data set who were treated with IV tissue plasminogen activator between April 2003 and September 2009 and had complete data on lipid profiles and complications. Potential predictors of sICH were tested in univariate and multivariate analysis. Results-The analysis included 22 216 IV tissue plasminogen activator-treated acute ischemic stroke patients. Overall, 1104 (4.97%) experienced sICH (National Institute of Neurological Disorders and Stroke definition). In univariate analysis, patients with sICH were more often taking antihypertensive, lipid-lowering, and diabetes mellitus medications. There was no relationship between low density lipoprotein or total cholesterol and sICH in univariate analysis. However, the risk of sICH increased with higher high density lipoprotein, 6.1% in Q4 versus 4.7% in Q1, P=0.0013; and lower triglyceride levels, 5.9% in Q1 versus 4.2% in Q4, P<0.0001. In multivariable models, although the high density lipoprotein and triglyceride levels were modestly associated with sICH, low density lipoprotein and total cholesterol were not. Lipid-lowering medications were not independently associated with sICH. Conclusions-We found that low density lipoprotein and total cholesterol levels are not associated with risk of sICH after tissue plasminogen activator, although higher high density lipoprotein and lower triglyceride levels were modest risk factors. Lipid-lowering medications are not associated with risk of sICH. (Stroke. 2013;44:1354-1359.) C1 [Messe, Steven R.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Pervez, Muhammad A.; Siddique, Khawaja A.; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Hellkamp, Anne S.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Messe, SR (reprint author), Hosp Univ Penn, 3400 Spruce St,3 W Gates Bldg, Philadelphia, PA 19104 USA. EM messe@mail.med.upenn.edu OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Janssen Pharmaceutical Companies of Johnson Johnson; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; AHA Pharmaceutical Roundtable; National Institutes of Health; WL Gore; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi-Aventis FX Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported, in part, by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, and the AHA Pharmaceutical Roundtable. A Young Investigator Database Research Seed Grant was sponsored by the Council on Clinical Cardiology.; Dr Messe has served on the speaker's bureau for Boehringer-Ingelheim (modest, ended 4/2011) and receives research support from the National Institutes of Health (significant) and WL Gore (modest). Dr Peterson has served as a consultant for AstraZeneca (modest). Dr Fonarow serves as a member of the GWTG steering committee, receives research support from the National Institutes of Health (significant), served as a consultant to Pfizer (modest); and is an employee of the University of California, which holds a patent on retriever devices for stroke (significant). Dr Smith serves as a member of the GWTG Steering Subcommittee. A.S. Hellkamp is a member of the Duke Clinical Research Institute, which serves as the AHA GWTG data coordinating Center. Dr Saver serves as an unpaid volunteer on Get With The Guidelines Committees and is an employee of the University of California, which receives payments for his service as a scientific consultant regarding trial design and conduct to Covidien, CoAxia, Talacris, Brainsgate, and Sygnis, and which holds a patent on retriever devices for stroke. Dr Bhatt serves on 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, and Takeda; Research Grants (significant): Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-Aventis, and The Medicines Company. He serves as the chair of the AHA GWTG Science Subcommittee. Dr Schwamm serves as chair of the AHA/ASA's GWTG Steering Committee, a consultant to the Research Triangle Institute and to the Massachusetts Department of Public Health, and serves on the Steering Committee for Lundbeck's DIAS4 clinical trial. The other authors have no conflicts to report. NR 31 TC 3 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2013 VL 44 IS 5 BP 1354 EP 1359 DI 10.1161/STROKEAHA.111.671966 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 131WZ UT WOS:000318030000041 PM 23493734 ER PT J AU Kimberly, WT Wang, Y Pham, L Furie, KL Gerszten, RE AF Kimberly, W. Taylor Wang, Yu Ly Pham Furie, Karen L. Gerszten, Robert E. TI Metabolite Profiling Identifies a Branched Chain Amino Acid Signature in Acute Cardioembolic Stroke SO STROKE LA English DT Article DE cerebrospinal fluid; liquid chromatography; mass spectrometry; metabolomics; transient ischemic attack stroke ID TUMOR-NECROSIS-FACTOR; CAUSATIVE CLASSIFICATION; ISCHEMIC-STROKE; INFARCT VOLUME; METABOLOMICS; BIOMARKERS; RATS; DISEASE; SYSTEM; BLOOD AB Background and Purpose-There is limited information about changes in metabolism during acute ischemic stroke. The identification of changes in circulating plasma metabolites during cerebral infarction may provide insight into disease pathogenesis and identify novel biomarkers. Methods-We performed filament occlusion of the middle cerebral artery of Wistar rats and collected plasma and cerebrospinal fluid 2 hours after the onset of ischemia. Plasma samples from control and patients with acute stroke were also analyzed. All samples were examined using liquid chromatography followed by tandem mass spectrometry. Positively charged metabolites, including amino acids, nucleotides, and neurotransmitters, were quantified using electrospray ionization followed by scheduled multiple reaction monitoring. Results-The concentrations of several metabolites were altered in the setting of cerebral ischemia. We detected a reduction in the branched chain amino acids (valine, leucine, isoleucine) in rat plasma, rat cerebrospinal fluid, and human plasma compared with respective controls (16%, 23%, and 17%, respectively; P<0.01 for each). In patients, lower branched chain amino acids levels also correlated with poor neurological outcome (modified Rankin Scale, 0-2 versus 3-6; P=0.002). Conclusions-Branched chain amino acids are reduced in ischemic stroke, and the degree of reduction correlates with worse neurological outcome. Whether branched chain amino acids are in a causal pathway or are an epiphenomenon of ischemic stroke remains to be determined. (Stroke. 2013;44:1389-1395.) C1 [Kimberly, W. Taylor; Ly Pham] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Kimberly, W. Taylor; Ly Pham] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. [Kimberly, W. Taylor; Wang, Yu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Furie, Karen L.] Brown Univ, Dept Neurol, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Kimberly, WT (reprint author), Lunder 644,55 Fruit St, Boston, MA 02114 USA. EM wtkimberly@partners.org; gerszten.robert@mgh.harvard.edu FU Clinical Investigator Training Program: Beth Israel Deaconess Medical Center, Harvard Medical School; Pfizer Inc; Merck and Co; National Institute of Health (NIH) [K23NS076597, NIH 5P50NS051343-07, NIH R01HL096738, R01HL098280] FX This study was supported by the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center, Harvard Medical School, in collaboration with Pfizer Inc and Merck and Co (Dr Kimberly), by National Institute of Health (NIH) K23NS076597 (Dr Kimberly), NIH 5P50NS051343-07 (Dr Furie), and NIH R01HL096738 and R01HL098280 (Dr Gerstzen).; Dr Kimberly discloses a research grant (National Institute of Health [NIH]; significant) and Dr Gerszten discloses a research grant (NIH; significant). NR 41 TC 13 Z9 13 U1 6 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2013 VL 44 IS 5 BP 1389 EP + DI 10.1161/STROKEAHA.111.000397 PG 20 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 131WZ UT WOS:000318030000046 PM 23520238 ER PT J AU James, SK Pieper, KS Cannon, CP Storey, RF Becker, RC Steg, PG Wallentin, L Harrington, RA AF James, Stefan K. Pieper, Karen S. Cannon, Christopher P. Storey, Robert F. Becker, Richard C. Steg, Philippe Gabriel Wallentin, Lars Harrington, Robert A. CA PLATO Study Grp TI Ticagrelor in Patients With Acute Coronary Syndromes and Stroke Interpretation of Subgroups in Clinical Trials SO STROKE LA English DT Editorial Material DE Acute coronary syndromes; clinical trial; platelet inhibition; Stroke ID OUTCOMES PLATO TRIAL; PLATELET INHIBITION; CLOPIDOGREL; HISTORY C1 [James, Stefan K.; Wallentin, Lars] Uppsala Univ, Dept Med Sci, SE-75237 Uppsala, Sweden. [James, Stefan K.; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, SE-75237 Uppsala, Sweden. [Pieper, Karen S.; Becker, Richard C.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Steg, Philippe Gabriel] INSERM, U698, Paris, France. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, Assistance Publ Hop Paris, F-75877 Paris, France. [Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. RP James, SK (reprint author), Uppsala Univ, Dept Med Sci, Dag Hammarskjolds Vag 14B, SE-75237 Uppsala, Sweden. EM Stefan.James@ucr.uu.se NR 7 TC 5 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2013 VL 44 IS 5 BP 1477 EP 1479 DI 10.1161/STROKEAHA.111.000514 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 131WZ UT WOS:000318030000064 PM 23572474 ER PT J AU Shikari, H Antin, JH Dana, R AF Shikari, Hasanain Antin, Joseph H. Dana, Reza TI Ocular Graft-versus-Host Disease: A Review SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE allogeneic bone marrow transplantation; hematopoietic stem cells; graft-versus-host disease; ocular GVHD; ocular surface disease; dry eye disease ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; DRY-EYE DISEASE; REGULATORY T-CELLS; TOPICAL CYCLOSPORINE 0.05-PERCENT; MINOR HISTOCOMPATIBILITY ANTIGENS; MATCHED RELATED DONORS; TOTAL-BODY IRRADIATION AB Graft-versus-host disease (GVHD) is a common cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic findings involving the skin, gastrointestinal tract, and liver often overshadow the other manifestations of GVHD. Ocular surface disease remains the most common cause of long-term morbidity in GVHD. Herein, the etiology, pathophysiology, clinical manifestations, and treatment of acute and chronic systemic GVHD are reviewed, with a focus on ocular GVHD. (Surv Ophthalmol 58:233-251, 2013. (C) 2013 Elsevier Inc. All rights reserved.) C1 [Shikari, Hasanain; Dana, Reza] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Shikari, Hasanain; Dana, Reza] Schepens Eye Res Inst, Boston, MA 02114 USA. [Shikari, Hasanain; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Antin, Joseph H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Antin, Joseph H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu NR 181 TC 29 Z9 29 U1 0 U2 7 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 MAY-JUN PY 2013 VL 58 IS 3 BP 233 EP 251 DI 10.1016/j.survophthal.2012.08.004 PG 19 WC Ophthalmology SC Ophthalmology GA 133JO UT WOS:000318134900002 PM 23541042 ER PT J AU Avila-Tang, E Elf, JL Cummings, KM Fong, GT Hovell, MF Klein, JD McMillen, R Winickoff, JP Samet, JM AF Avila-Tang, Erika Elf, Jessica L. Cummings, K. Michael Fong, Geoffrey T. Hovell, Melbourne F. Klein, Jonathan D. McMillen, Robert Winickoff, Jonathan P. Samet, Jonathan M. TI Assessing secondhand smoke exposure with reported measures SO TOBACCO CONTROL LA English DT Review ID ENVIRONMENTAL TOBACCO-SMOKE; NUTRITION EXAMINATION SURVEY; ACTIVITY PATTERN SURVEY; COTININE CONCENTRATIONS; PASSIVE SMOKING; ETS EXPOSURE; LUNG-CANCER; ASTHMA MANAGEMENT; URINARY COTININE; LATINO CHILDREN AB Non-smokers are exposed to tobacco smoke from the burning cigarette and the exhaled smoke from smokers. In spite of decades of development of approaches to assess secondhand smoke exposure (SHSe), there are still unresolved methodological issues. This manuscript summarises the scientific evidence on the use of SHSe reported measures and their methods, objectives, strengths and limitations; and discusses best practices for assessing behaviour leading to SHSe for lifetime and immediate or current SHSe. Recommendations for advancing measurement science of SHSe are provided. Behavioural measures of SHSe commonly rely on self-reports from children and adults. Most commonly, the methodology includes self, proxy and interview-based reporting styles using retrospective recall or diary-style reporting formats. The reporting method used will vary based upon the subject of interest, assessment objectives and cultural context. Appropriately implemented, reported measures of SHSe provide an accurate, timely and cost-effective method for assessing exposure time, location and quantity in a wide variety of populations. C1 [Avila-Tang, Erika] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Avila-Tang, Erika; Elf, Jessica L.] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, Baltimore, MD 21205 USA. [Avila-Tang, Erika; Klein, Jonathan D.; McMillen, Robert; Winickoff, Jonathan P.] Amer Acad Pediat, Julius B Richmond Ctr Excellence, Elk Grove Village, IL USA. [Cummings, K. Michael] Med Univ S Carolina, Charleston, SC 29425 USA. [Fong, Geoffrey T.] Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada. [Fong, Geoffrey T.] Ontario Inst Canc Res, Toronto, ON, Canada. [Hovell, Melbourne F.] San Diego State Univ, Ctr Behav Epidemiol, San Diego, CA 92182 USA. [McMillen, Robert] Mississippi State Univ, Dept Psychol, Starkville, MS USA. [Winickoff, Jonathan P.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Samet, Jonathan M.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. RP Avila-Tang, E (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, 2213 McElderry St,4th Floor, Baltimore, MD 21205 USA. EM etang@jhsph.edu RI Fong, Geoffrey/H-2810-2014 OI Fong, Geoffrey/0000-0001-9098-6472 FU Flight Attendant Medical Research Institute to the Johns Hopkins Center of Excellence; University of California, San Francisco Bland Lane Center of Excellence; American Academy of Pediatrics Julius B Richmond Center of Excellence FX This work was supported by grants from the Flight Attendant Medical Research Institute to the Johns Hopkins Center of Excellence; the University of California, San Francisco Bland Lane Center of Excellence; and the American Academy of Pediatrics Julius B Richmond Center of Excellence. The funding organisation had no role in the preparation of the manuscripts. NR 60 TC 23 Z9 24 U1 3 U2 17 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 EI 1468-3318 J9 TOB CONTROL JI Tob. Control PD MAY PY 2013 VL 22 IS 3 BP 156 EP 163 DI 10.1136/tobaccocontrol-2011-050296 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 126DC UT WOS:000317590900005 PM 22949496 ER PT J AU Nguyen, KH Wright, RJ Sorensen, G Subramanian, SV AF Nguyen, K. H. Wright, R. J. Sorensen, G. Subramanian, S. V. TI Association between local indoor smoking ordinances in Massachusetts and cigarette smoking during pregnancy: a multilevel analysis SO TOBACCO CONTROL LA English DT Article ID TOBACCO CONTROL; AIR LAWS; REGULATIONS; BEHAVIORS; WORKPLACE; POLICIES; LEGISLATION; ATTITUDES; CESSATION; STRENGTH AB Objective To estimate the association between local clean indoor air ordinances and prenatal maternal smoking across 351 municipalities in Massachusetts before the 2004 statewide ban and to test the effect of time since ordinance adoption on the association. Methods The authors linked 2002 birth certificate data of women who gave birth in the state and reported a Massachusetts residence (n = 67 584) to a database of indoor smoking ordinances in all municipalities. Multilevel regression models accounting for individual- and municipality-level variables estimate the associations between the presence of local smoking ordinances, strength of the ordinances, time since ordinance adoption and prenatal smoking. Results Compared with those living in municipalities with no ordinances, women living in municipalities with a smoking ordinance had lower odds of prenatal smoking (OR = 0.72, CI = 0.53 to 0.98). No effect was found for 100% smoke-free ordinances. For the analyses testing the effect of time, pregnant women living in municipalities with ordinances enacted >2 years were less likely to smoke than those in municipalities with more recent (<1 year) ordinances. Conclusions Preventing smoking among women of reproductive age is a public health priority. This study suggests that indoor smoking ordinances were associated with lower prenatal smoking prevalence and the favourable effect increased over time. Findings highlight the public health benefit of tobacco control policies. C1 [Nguyen, K. H.] Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94111 USA. [Wright, R. J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Wright, R. J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Sorensen, G.; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Soc Hlth & Human Dev, Boston, MA 02115 USA. [Sorensen, G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Nguyen, KH (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, 1450 3rd St, San Francisco, CA 94111 USA. EM nguyenk@cc.ucsf.edu FU National Cancer Institute Diversity Supplement Award [R01CA129096]; National Heart, Lung, and Blood Institute Career Development Award [K25 HL081275]; Robert Wood Johnson Investigator Award in Health Policy Research; National Cancer Institute [K05 CA108663] FX KHN received support from the National Cancer Institute Diversity Supplement Award (R01CA129096). SVS was supported by the National Heart, Lung, and Blood Institute Career Development Award (K25 HL081275) and the Robert Wood Johnson Investigator Award in Health Policy Research. GS was supported by the National Cancer Institute (K05 CA108663). NR 27 TC 11 Z9 11 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD MAY PY 2013 VL 22 IS 3 BP 184 EP 189 DI 10.1136/tobaccocontrol-2011-050157 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 126DC UT WOS:000317590900016 PM 22166267 ER PT J AU Vagefi, PA Qian, JJ Carlson, DM Aparici, CM Hirose, R Vincenti, F Wojciechowski, D AF Vagefi, Parsia A. Qian, Jesse J. Carlson, David M. Aparici, Carina Mari Hirose, Ryutaro Vincenti, Flavio Wojciechowski, David TI Native renal function after combined liver-kidney transplant for type 1 hepatorenal syndrome: initial report on the use of postoperative Technetium-99 m-mercaptoacetyltriglycine scans SO TRANSPLANT INTERNATIONAL LA English DT Article DE end-stage liver disease; technetium-99 m-mercaptoacetyltriglycine renogram; renal replacement therapy ID MELD ERA; OUTCOMES AB Type 1 hepatorenal syndrome (HRS) is characterized by rapid deterioration of renal function. We sought to assess native kidney function after combined kidney-liver transplant (CLKTx) performed for type 1 HRS. We performed a retrospective, cross-sectional, single-center study. All patients with Type 1 HRS who received a CLKTx at the University of California, San Francisco from 1997 to 2007 were screened for enrollment. Patients with a baseline estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 were eligible. Twenty-three patients were identified and consented to receive a Technetium-99 m-mercaptoacetyltriglycine (MAG3) nuclear scan to measure the native kidney contribution to overall renal function. Only 4 of the 23 subjects (17.4%) demonstrated native renal function that consisted of a contribution 50% of total renal function. Several factors and comorbidities such as age, gender, race, duration of HRS, need for and duration of renal replacement therapy, need for pressors, urine sodium, proteinuria, and use of octreotide/midodrine were analyzed and not found to be significant in predicting native renal function. The assessment of post-transplant native renal function following CLKTx may allow for improved accuracy in identifying the patients in need of CLKTx, and thus allow for greater optimization of dual-organ allocation strategies in patients with concomitant liver and renal failure. C1 [Vagefi, Parsia A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Qian, Jesse J.] Kaiser Permanente, Med Grp, Stockton, CA USA. [Carlson, David M.; Aparici, Carina Mari] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Hirose, Ryutaro] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Vincenti, Flavio; Wojciechowski, David] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Wojciechowski, D (reprint author), Univ Calif San Francisco, 400,Parnassus Ave Suite A701, San Francisco, CA 94143 USA. EM david.wojciechowski@ucsf.edu FU ASTS-Novartis Fellowship in Transplantation Award; AST/Roche Clinical Science Fellowship grant FX This study was funded by an ASTS-Novartis Fellowship in Transplantation Award (PAV) and AST/Roche Clinical Science Fellowship grant (JJQ). NR 16 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD MAY PY 2013 VL 26 IS 5 BP 471 EP 476 DI 10.1111/tri.12066 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 132DV UT WOS:000318049000006 PM 23384317 ER PT J AU Lee, J Hwang, YJ Shin, JY Lee, WC Wie, J Kim, KY Lee, MY Hwang, D Ratan, RR Pae, AN Kowall, NW So, I Kim, JI Ryu, H AF Lee, Junghee Hwang, Yu Jin Shin, Jong-Yeon Lee, Won-Chul Wie, Jinhong Kim, Ki Yoon Lee, Min Young Hwang, Daehee Ratan, Rajiv R. Pae, Ae Nim Kowall, Neil W. So, Insuk Kim, Jong-Il Ryu, Hoon TI Epigenetic regulation of cholinergic receptor M1 (CHRM1) by histone H3K9me3 impairs Ca2+ signaling in Huntington's disease SO ACTA NEUROPATHOLOGICA LA English DT Article DE H3K9me3; Epigenomes; Huntington's disease; Cholinergic receptor M1; Heterochromatin ID STRIATAL CELLS; H3; HETEROCHROMATIN; METHYLATION; EXPRESSION; NEURONS; ESET; METHYLTRANSFERASE; INTERNEURONS; MODULATION AB Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded trinucleotide CAG repeat in the gene coding for huntingtin. Deregulation of chromatin remodeling is linked to the pathogenesis of HD but the mechanism remains elusive. To identify what genes are deregulated by trimethylated histone H3K9 (H3K9me3)-dependent heterochromatin, we performed H3K9me3-ChIP genome-wide sequencing combined with RNA sequencing followed by platform integration analysis in stable striatal HD cell lines (STHdhQ7/7 and STHdhQ111/111) cells. We found that genes involving neuronal synaptic transmission including cholinergic receptor M1 (CHRM1), cell motility, and neuronal differentiation pathways are downregulated while their promoter regions are highly occupied with H3K9me3 in HD. Moreover, we found that repression of CHRM1 gene expression by H3K9me3 impairs Ca2+-dependent neuronal signal transduction in stable cell lines expressing mutant HD protein. Thus, our data indicate that the epigenetic modifications, such as aberrant H3K9me3-dependent heterochromatin plasticity, directly contribute to the pathogenesis of HD. C1 [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] Vet Affairs Boston Healthcare Syst, Boston, MA 02130 USA. [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Hwang, Yu Jin; Lee, Won-Chul; Kim, Ki Yoon; Ryu, Hoon] Seoul Natl Univ, Coll Med, WCU Neurocyt Grp, Seoul, South Korea. [Shin, Jong-Yeon; Lee, Won-Chul; Kim, Jong-Il] Seoul Natl Univ, Coll Med, Genome Med Inst, Seoul, South Korea. [Wie, Jinhong; So, Insuk] Seoul Natl Univ, Coll Med, Dept Physiol & Biomed Sci, Seoul, South Korea. [Shin, Jong-Yeon; Kim, Jong-Il] Psoma Therapeut Inc, Seoul, South Korea. [Lee, Min Young; Hwang, Daehee] POSTECH, Dept Chem Engn, Pohang, South Korea. [Lee, Min Young; Hwang, Daehee] POSTECH, Sch Interdisciplinary Biosci & Bioengn, Pohang, South Korea. [Ratan, Rajiv R.] Burke Med Res Inst, White Plains, NY USA. [Pae, Ae Nim] Korea Inst Sci & Technol KIST, Brain Sci Inst, Ctr Neuromed, Seoul 136791, South Korea. [Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Ryu, H (reprint author), Boston Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, Bldg 1A,Rm109,150 South Huntington Ave, Boston, MA 02130 USA. EM hoonryu@bu.edu RI KIM, JONG-IL/D-1019-2011; Kowall, Neil/G-6364-2012 OI KIM, JONG-IL/0000-0002-7240-3744; Kowall, Neil/0000-0002-6624-0213 FU WCU [800-20080848]; MEST of Korea [2010-0029-403]; KIST; NIH [NS 067283-01A1] FX We thank to Dr. Marcy MacDonald for STHdhQ7/7 and STHdhQ111/111 cells and to Min-Kyung Jung for her technical assistance. This study was supported by WCU Neurocytomics Program Grant (800-20080848) (H. R.) and SRC Grant (2010-0029-403) (H. R.) from MEST of Korea, Flagship Grant (H. R.) from KIST and NIH NS 067283-01A1 (H.R.). NR 36 TC 19 Z9 19 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAY PY 2013 VL 125 IS 5 BP 727 EP 739 DI 10.1007/s00401-013-1103-z PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 130MY UT WOS:000317923400009 PM 23455440 ER PT J AU Tondo, L Baldessarini, RJ Vazquez, G Lepri, B Visioli, C AF Tondo, L. Baldessarini, R. J. Vazquez, G. Lepri, B. Visioli, C. TI Clinical responses to antidepressants among 1036 acutely depressed patients with bipolar or unipolar major affective disorders SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE antidepressant response; bipolar disorder; depression; major depressive disorder; switching ID ELECTROCONVULSIVE-THERAPY; CYCLE ACCELERATION; CONTROLLED-TRIALS; MANIA; METAANALYSIS; CONTROVERSY; SYMPTOMS; STATES AB Tondo L, Baldessarini RJ, Vazquez G, Lepri B, Visioli C. Clinical responses to antidepressants among 1036 acutely depressed patients with bipolar or unipolar major affective disorders. Objective Whether responses to antidepressants differ in bipolar and unipolar depression remains unresolved. Method We analyzed patient characteristics and outcomes of antidepressant treatment of 1036 depressed patients with bipolar-I or bipolar-II disorder, or unipolar major depression, using bivariate and multivariate methods and survival analysis, testing the hypothesis that responses would be superior in unipolar depression. Results Antidepressants were given to 84.8% (878/1036) of depressed patients: 58.9% of 93 bipolar-I, 80.1% of 117 bipolar-II, and 91.3% of 668 unipolar disorder cases. The 158 not given antidepressants had more manias/year, spent more months in mania and depression, and were far more likely to receive mood stabilizers or antipsychotics long term. Improvement of HDRS21 depression ratings ranked: bipolar-II (69.6%)>bipolar-I (62.9%)>unipolar (57.9%; P<0.0001), independent of initial illness severity. Responder rates (50% improved without switching) ranked: bipolar-II (77.0%)>bipolar-I (71.6%)>unipolar (61.7%; P<0.0001). Remission rates (final HDRS<7) ranked: 54.0%, 50.6%, and 40.8% respectively (P=0.02); 67.5% remitted within 12weeks of treatment. Survival-computed median time to remission (15.0weeks, overall) was shortest for bipolar-II patients (10.7weeks). The 3-month risk of switching into maniahypomania ranked: bipolar-II (15.8%)>bipolar-I (8.60%)>unipolar (0.56%). Multivariate modeling found bipolar diagnosis, shorter latency to remission, more recent trial year, and fewer weeks depressed before treatment to be associated with greater percent improvement of HDRS ratings. Conclusion Selective use of antidepressants with or without mood stabilizers in non-agitated, depressed bipolar disorder patients for short periods was effective with moderate risk of potentially dangerous, manic mood elevation. C1 [Tondo, L.; Baldessarini, R. J.; Vazquez, G.] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Int Consortium Bipolar Disorder Res, Boston, MA 02114 USA. [Tondo, L.; Lepri, B.; Visioli, C.] Ctr Lucio Bini Mood Disorders Ctr, Cagliari, Italy. [Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Vazquez, G.] Univ Palermo, Dept Neurosci, Buenos Aires, DF, Argentina. RP Tondo, L (reprint author), McLean Hosp, Mailman Res Ctr 212, 115 Mill St, Belmont, MA 02478 USA. EM ltondo@mclean.harvard.edu FU Lucio Bini Private Donors Mood Disorders Research Fund; Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund FX Supported in part by the Lucio Bini Private Donors Mood Disorders Research Fund (to LT), by a grant from the Bruce J. Anderson Foundation, and by the McLean Private Donors Psychopharmacology Research Fund (to RJB). NR 40 TC 27 Z9 27 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAY PY 2013 VL 127 IS 5 BP 355 EP 364 DI 10.1111/acps.12023 PG 10 WC Psychiatry SC Psychiatry GA 127VI UT WOS:000317726500003 PM 23121222 ER PT J AU Ahluwalia, SC Leos, RL Goebel, JR Asch, SM Lorenz, KA AF Ahluwalia, Sangeeta C. Leos, Rosana L. Goebel, Joy R. Asch, Steven M. Lorenz, Karl A. TI Provider Approaches to Palliative Dyspnea Assessment: Implications for Informatics-Based Clinical Tools SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE dyspnea; qualitative research; electronic health records; clinical informatics; palliative care; user-computer interface ID PHYSICIAN ORDER ENTRY; QUALITY-OF-LIFE; UNITED-STATES; RESPIRATORY-DISEASES; CONSENSUS STATEMENT; ANXIETY DISORDERS; PRIMARY-CARE; LUNG-CANCER; MANAGEMENT; BREATHLESSNESS AB Aim: To understand provider practices around dyspnea assessment to inform the development of an electronic medical record (EMR)-based dyspnea assessment module in an inpatient palliative care consultation template. Design: Qualitative analysis of palliative care provider interviews. Results: Three themes emerged: (1) integration of patient self-report of breathlessness with a clinical observation of dyspnea; (2) identification of patients for dyspnea assessment based on perceived patient need; and (3) variability in preferences for and use of existing severity scales for dyspnea. Conclusions: The assessment approaches described by providers underscore the challenge of developing an informatics tool that supports the natural clinical experience and facilitates standardized care. The complexity of the dyspnea assessment process and variation in provider practices necessitate a level of flexibility and choice to be built into a computer-based tool. C1 [Ahluwalia, Sangeeta C.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA 90064 USA. [Ahluwalia, Sangeeta C.; Asch, Steven M.; Lorenz, Karl A.] RAND Corp, Santa Monica, CA USA. [Ahluwalia, Sangeeta C.; Leos, Rosana L.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Goebel, Joy R.] Calif State Univ Long Beach, Sch Nursing, Long Beach, CA 90840 USA. [Goebel, Joy R.; Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.] Vet Adm Palo Alto Healthcare Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Ahluwalia, SC (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111-G, Los Angeles, CA 90064 USA. EM sangeeta.c.ahluwalia@gmail.com FU Department of Veterans Affairs Comprehensive End-of-Life Care Initiative, Office of Patient Care Services; Office of Academic Affiliation's VA Associated Health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Department of Veterans Affairs Comprehensive End-of-Life Care Initiative, Office of Patient Care Services. Dr Ahluwalia was supported by an Office of Academic Affiliation's VA Associated Health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence. NR 64 TC 1 Z9 1 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD MAY PY 2013 VL 30 IS 3 BP 231 EP 238 DI 10.1177/1049909112448922 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 127CW UT WOS:000317674300002 PM 22669935 ER PT J AU Howitt, BE Herfs, M Brister, K Oliva, E Longtine, J Hecht, JL Nucci, MR AF Howitt, Brooke E. Herfs, Michael Brister, Kathriel Oliva, Esther Longtine, Janina Hecht, Jonathan L. Nucci, Marisa R. TI Intestinal-type Endocervical Adenocarcinoma In Situ An Immunophenotypically Distinct Subset of AIS Affecting Older Women SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE cervical adenocarcinoma in situ; intestinal; HPV; p16 ID DIFFERENT HISTOLOGICAL SUBTYPES; HUMAN-PAPILLOMAVIRUS; CERVICAL ADENOCARCINOMA; UTERINE CERVIX; GLANDULAR LESIONS; GASTRIC MORPHOLOGY; EXPRESSION; P16(INK4A); DIAGNOSIS; INSITU AB Conventional endocervical adenocarcinoma in situ (cAIS) is typically strongly and diffusely positive for p16 with a high Ki67 index consistent with its frequent association with high-risk human papillomavirus (HPV) infection. The intestinal variant (iAIS) is less common, and its relationship to HPV infection has not been thoroughly examined. This study compares the clinicopathologic features, frequency of HPV infection, and expression of CDX2 and surrogate biomarkers of HPV infection (p16, Ki67) in cAIS with those of iAIS. A total of 86 cases with a diagnosis of AIS (49 iAIS, 37 cAIS) were identified from our multi-institutional files. Of these, 13 iAIS and 20 cAIS cases had slides and tissue available for histopathologic review, immunohistochemical analysis, and molecular tests. All 86 cases were used to evaluate clinical parameters; however, HPV DNA analysis and immunohistochemical analysis for p16, MIB-1, CDX2, and p53 were performed only on those cases with available slides or paraffin blocks. The average age at diagnosis was significantly higher in iAIS compared with that in cAIS (44.5 vs. 32.6 y) (P = 0.0001). All 20 cAIS cases showed moderate to strong and diffuse p16 staining; however, only 9/13 iAIS cases showed this degree of p16 staining, whereas 4/13 (31%) iAIS cases showed weak and patchy distribution (P < 0.02). Only 6/9 (67%) iAIS cases were positive for either HPV type 18 (5) or 33 (1), in contrast to 11/11 conventional cAIS (P = 0.04). Similarly, 12/14 cAIS, but only 5/13 iAIS, cases showed a high Ki67 proliferative index. CDX2 was positive in all iAIS cases, whereas p53 was negative. Most iAIS cases are positive for high-risk HPV and show moderate to strong and diffuse p16 staining; however, a subset of iAIS shows variable staining with p16 and Ki67, is not associated with HPV, and occurs in a distinctly older age group suggesting an alternative pathogenesis. Awareness that iAIS can show variable staining for p16 and Ki67 is important when resolving problematic endocervical lesions, particularly in small biopsies with unusual p16 staining patterns. C1 [Howitt, Brooke E.; Longtine, Janina; Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Brister, Kathriel; Hecht, Jonathan L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Herfs, Michael] Univ Liege, Dept Pathol, Liege, Belgium. RP Nucci, MR (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. EM mnucci@partners.org NR 30 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 2013 VL 37 IS 5 BP 625 EP 633 DI 10.1097/PAS.0b013e318285be00 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 126ZP UT WOS:000317663100001 PM 23552379 ER PT J AU Lim, D Alvarez, T Nucci, MR Gilks, B Longacre, T Soslow, RA Oliva, E AF Lim, Diana Alvarez, Teresa Nucci, Marisa R. Gilks, Blake Longacre, Teri Soslow, Robert A. Oliva, Esther TI Interobserver Variability in the Interpretation of Tumor Cell Necrosis in Uterine Leiomyosarcoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE uterus; leiomyosarcoma; tumor cell necrosis ID SMOOTH-MUSCLE TUMORS; MITOTICALLY ACTIVE LEIOMYOMAS; PHOSPHOHISTONE H3 PHH3; SOFT-TISSUE SARCOMAS; PROGNOSTIC-FACTORS; MULTIVARIATE-ANALYSIS; GRADE LEIOMYOSARCOMA; UTERUS; PATHOLOGY; NEOPLASMS AB On the basis of the most recent World Health Organization classification, distinction of leiomyosarcoma (LMS) from leiomyoma is based on the presence of the following morphologic criteria: (1) nuclear atypia; (2) mitotic index; and (3) tumor cell necrosis (TCN). Unlike ischemic-type necrosis, which may be seen in benign and malignant smooth muscle tumors (SMTs), TCN is thought to be found only in LMS. The distinction between these 2 types of necrosis can be challenging, especially during the early stages, when necrotic foci are small, or when overlapping features are identified. The aim of this study is to assess the interobserver variability in the interpretation of TCN in uterine LMS. Thirty-four LMS cases were retrieved, and a representative hematoxylin and eosin slide showing 1 area of necrosis was selected from each case. Pathologists from 6 different institutions subspecializing in gynecologic pathology performed a blinded, independent review of the slides. Using the current World Health Organization criteria for assessment of TCN, they had to classify the necrotic foci into: (1) TCN; (2) no TCN; or (3) indeterminate for TCN. Agreement among panelists was categorized as: full-all pathologists in agreement; partial-4 or 5 pathologists in agreement; no agreement-<= 3 pathologists placing the case into the same category. Full agreement regarding the presence or absence of TCN was reached in 12 cases (35%) (7 thought to show TCN); partial agreement in 16 (47%); and no general consensus was obtained in 6 (18%). Overall, the level of agreement was moderate (kappa = 0.436). In 8 of 34 instances (23.5%), >= 1 pathologist made a diagnosis of "TCN" and >= 1 pathologist made the diagnosis of "no TCN" for the same slide. The number of cases diagnosed as "indeterminate for TCN" by each pathologist ranged from 0 to 10 with a mean of 5.8. In 20 cases, at least 1 pathologist diagnosed "indeterminate for TCN" (59%), at least 2 and 3 were undecided in 10 (29%) and 4 (12%) cases, respectively, and 4 pathologists diagnosed "indeterminate for TCN" in 1 instance. When excluding foci of necrosis diagnosed as "indeterminate" by any pathologist, disagreement occurred in 2/14 (14%) cases. From these results we conclude that the level of interobserver agreement among expert gynecologic pathologists in the assessment of TCN in uterine SMTs is only moderate. These results further reiterate the importance of assessing for both nuclear atypia and mitotic activity when differentiating between benign and malignant SMTs and not relying solely on the presence of TCN. C1 [Lim, Diana] Natl Univ Hlth Syst, Singapore, Singapore. [Alvarez, Teresa] Hosp Univ Bellvitge, Barcelona, Spain. [Nucci, Marisa R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Longacre, Teri] Stanford Univ, Stanford, CA 94305 USA. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gilks, Blake] Vancouver Gen Hosp, Vancouver, BC, Canada. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit st, Boston, MA 02114 USA. EM eoliva@partners.org OI Soslow, Robert/0000-0002-7269-5898 NR 55 TC 13 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 2013 VL 37 IS 5 BP 650 EP 658 DI 10.1097/PAS.0b013e3182851162 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 126ZP UT WOS:000317663100004 PM 23552382 ER PT J AU Regue, L Mou, F Avruch, J AF Regue, Laura Mou, Fan Avruch, Joseph TI G protein-coupled receptors engage the mammalian Hippo pathway through F-actin F-Actin, assembled in response to Galpha(12/13) induced RhoA-GTP, promotes dephosphorylation and activation of the YAP oncogene SO BIOESSAYS LA English DT Article DE F-actin; Galpha12; 13; G protein-coupled receptors; hippo; TAZ; YAP ID SIGNALING PATHWAY; TUMOR-SUPPRESSOR; GROWTH-CONTROL; TISSUE-GROWTH; CELL-PROLIFERATION; ALPHA-CATENIN; SIZE CONTROL; ORGAN SIZE; METASTASIS; KINASES AB The Hippo pathway, a cascade of protein kinases that inhibits the oncogenic transcriptional coactivators YAP and TAZ, was discovered in Drosophila as a major determinant of organ size in development. Known modes of regulation involve surface proteins that mediate cell-cell contact or determine epithelial cell polarity which, in a tissue-specific manner, use intracellular complexes containing FERM domain and actin-binding proteins to modulate the kinase activities or directly sequester YAP. Unexpectedly, recent work demonstrates that GPCRs, especially those signaling through Galpha12/13 such as the protease activated receptor PAR1, cause potent YAP dephosphorylation and activation. This response requires active RhoA GTPase and increased assembly of filamentous (F-)actin. Morever, cell architectures that promote F-actin assembly per se also activate YAP by kinase-dependent and independent mechanisms. These findings unveil the ability of GPCRs to activate the YAP oncogene through a newly recognized signaling function of the actin cytoskeleton, likely to be especially important for normal and cancerous stem cells. C1 [Regue, Laura; Mou, Fan; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Regue, Laura; Mou, Fan; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Regue, Laura; Mou, Fan; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NIH [DK17776, CA136567, DK057521] FX Work cited from the author's lab was supported by NIH grants DK17776, CA136567, and DK057521. NR 61 TC 10 Z9 11 U1 2 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAY PY 2013 VL 35 IS 5 BP 430 EP 435 DI 10.1002/bies.201200163 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 127BC UT WOS:000317668100008 PM 23450633 ER PT J AU Januzzi, JL Horne, BD Moore, SA Galenko, O Snow, GL Brunisholz, KD Muhlestein, JB Alharethi, R Carlquist, JF Budge, D Rasmussen, K Kfoury, AG AF Januzzi, James L. Horne, Benjamin D. Moore, Stephanie A. Galenko, Oxana Snow, Gregory L. Brunisholz, Kimberly D. Muhlestein, Joseph B. Alharethi, Rami Carlquist, John F. Budge, Deborah Rasmussen, Kismet Kfoury, Abdallah G. TI Interleukin receptor family member ST2 concentrations in patients following heart transplantation SO BIOMARKERS LA English DT Article DE Biomarkers; biopsy; heart transplantation; prognosis; rejection ID CARDIAC ALLOGRAFT-REJECTION; MHC CLASS-II; SOLUBLE ST2; MYOCARDIAL-INFARCTION; ACUTE DYSPNEA; TOLERANCE; PROTEIN; CELLS; IL-33 AB Objective: To evaluate soluble (s) ST2 as a biomarker of rejection, allograft vasculopathy and mortality after orthotopic heart transplantation (OHT). Methods: sST2 concentrations were measured in 241 patients following OHT. Results: Elevated sST2 was associated with cellular rejection (CR) >= 1R, with highest rates of CR in the 4th sST2 quartile (p = 0.003). No significant association between sST2 and antibody-mediated rejection or allograft vasculopathy was found. sST2 >= 30 ng/mL independently predicted death over 7-year follow-up (HR = 2.01; 95% CI 1.15-3.51; p = 0.01). Conclusion: Concentrations of sST2 are associated with the presence of CR and predict long-term mortality following OHT. C1 [Januzzi, James L.; Moore, Stephanie A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Horne, Benjamin D.; Snow, Gregory L.; Brunisholz, Kimberly D.; Muhlestein, Joseph B.; Alharethi, Rami; Budge, Deborah; Rasmussen, Kismet; Kfoury, Abdallah G.] Intermt Med Ctr, Cardiovasc Dept, Salt Lake City, UT USA. [Galenko, Oxana; Carlquist, John F.] LDS Hosp, Cardiovasc Mol Res Lab, Salt Lake City, UT USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org OI Snow, Gregory/0000-0001-8530-1037 FU Critical Diagnostics FX Dr Januzzi reports receiving grant support from Critical Diagnostics. Otherwise, no declarations of interest exist. NR 21 TC 9 Z9 10 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD MAY PY 2013 VL 18 IS 3 BP 250 EP 256 DI 10.3109/1354750X.2013.773081 PG 7 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 130NX UT WOS:000317926200009 PM 23557127 ER PT J AU Macaya, DJ Hayakawa, K Arai, K Spector, M AF Macaya, Daniel J. Hayakawa, Kazuhide Arai, Ken Spector, Myron TI Astrocyte infiltration into injectable collagen-based hydrogels containing FGF-2 to treat spinal cord injury SO BIOMATERIALS LA English DT Article DE Collagen; Fibroblast growth factor; Nerve tissue engineering; Chemotaxis; In vitro test; Spinal cord injury ID FIBROBLAST-GROWTH-FACTOR; HEPARAN-SULFATE PROTEOGLYCAN; INTRATHECAL DELIVERY-SYSTEM; FACTOR BFGF; FUNCTIONAL RECOVERY; GLIAL SCAR; RAT-BRAIN; REACTIVE ASTROCYTES; WHITE-MATTER; REGENERATION AB Astrocytes can play dual roles in the response to spinal cord injury (SCI) acting as both an inhibitory barrier and a trophic support for growth axons. Therefore, migration of these cells into the defect as opposed to forming a scar at the periphery, may promote axon regeneration through the lesion. However, infiltration requires the conformal filling of the cyst-like lesion, which often forms after SCI, with a biomaterial scaffold encouraging of astrocyte migration. For this application, we investigated injectable collagen-based hydrogels covalently cross-linked with genipin and incorporating fibroblast growth factor-2 (FGF-2) either freely or encapsulated within lipid microtubules (LMTs). An outgrowth assay was used to evaluate in vitro the number of primary rat astrocytes infiltrating into the collagen gels and the distance to which they infiltrated. The presence of FGF-2 within the encapsulating gel significantly increased the number of astrocytes within the gel, their penetration distance into the gel, and caused them to move out in a chain-like pattern, compared to control gels without FGF-2. Genipin cross-linking of the collagen gel decreased the number of infiltrating astrocytes, compared to the non-cross-linked control gel; however, incorporation of FGF-2-containing LMTs within genipin-cross-linked gels restored the astrocyte infiltration to levels approaching non-cross-linked gels incorporating FGF-2. Overall, injectable collagen-genipin hydrogels containing FGF-2-containing LMTs are a promising candidate for the treatment for SCI through the attraction of astrocytes into the graft. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Macaya, Daniel J.; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Macaya, Daniel J.] Harvard Massachusetts Inst Technol, Cambridge, MA USA. [Hayakawa, Kazuhide; Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Hayakawa, Kazuhide; Arai, Ken] Harvard Univ, Sch Med, Charlestown, MA USA. [Hayakawa, Kazuhide; Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Spector, M (reprint author), 150 S Huntington Ave,MS151, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU NSF Fellowship; VA Research Career Scientist Award; U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service FX D.M. was supported by an NSF Fellowship, and MS by a VA Research Career Scientist Award. The work was supported in part by the U.S. Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service. NR 58 TC 15 Z9 15 U1 5 U2 57 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAY PY 2013 VL 34 IS 14 BP 3591 EP 3602 DI 10.1016/j.biomaterials.2012.12.050 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 125IT UT WOS:000317534200006 PM 23414684 ER PT J AU Bunnell, CA Gross, AH Weingart, SN Kalfin, MJ Partridge, A Lane, S Burstein, HJ Fine, B Hilton, NA Sullivan, C Hagemeister, EE Kelly, AE Colicchio, L Szabatura, AH Winer, EP Salisbury, M Mann, S AF Bunnell, Craig A. Gross, Anne H. Weingart, Saul N. Kalfin, Michael Jason Partridge, Ann Lane, Sharon Burstein, Harold J. Fine, Barbara Hilton, Nancy A. Sullivan, Clare Hagemeister, Erin E. Kelly, Anne E. Colicchio, Lynn Szabatura, Audrea H. Winer, Eric P. Salisbury, Mary Mann, Susan TI High performance teamwork training and systems redesign in outpatient oncology SO BMJ QUALITY & SAFETY LA English DT Article ID PATIENT SAFETY; COMMUNICATION; CARE; TEAMS AB Background Oncology care is delivered largely in ambulatory settings by interdisciplinary teams. Treatments are often complex, extended in time, dispersed geographically and vulnerable to teamwork failures. To address this risk, we developed and piloted a team training initiative in the breast cancer programme at a comprehensive cancer centre. Methods Based on clinic observations, interviews with key staff and analyses of incident reports, we developed interventions to address four high-risk areas: (1) miscommunication of chemotherapy order changes on the day of treatment; (2) missing orders on treatment days without concurrent physician appointments; (3) poor follow-up with team members about active patient issues; and (4) conflict between providers and staff. The project team developed protocols and agreements to address team members' roles, responsibilities and behaviours. Results Using a train-the-trainer model, 92% of breast cancer staff completed training. The incidence of missing orders for unlinked visits decreased from 30% to 2% (p<0.001). Patient satisfaction scores regarding coordination of care improved from 93 to 97 (p=0.026). Providers, infusion nurses and support staff reported improvement in efficiency (75%, 86%, 90%), quality (82%, 93%, 93%) and safety (92%, 92%, 90%) of care, and more respectful behaviour (92%, 79%, 83%) and improved relationships among team members (91%, 85%, 92%). Although most clinicians reported a decrease in non-communicated changes, there was insufficient statistical power to detect a difference. Conclusions Team training improved communication, task coordination and perceptions of efficiency, quality, safety and interactions among team members as well as patient perception of care coordination. C1 [Bunnell, Craig A.; Partridge, Ann; Burstein, Harold J.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Gross, Anne H.; Kalfin, Michael Jason; Fine, Barbara; Hilton, Nancy A.; Sullivan, Clare; Hagemeister, Erin E.; Kelly, Anne E.; Colicchio, Lynn] Dana Farber Canc Inst, Dept Nursing & Patient Care Serv, Boston, MA 02215 USA. [Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Lane, Sharon] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA. [Szabatura, Audrea H.] Dana Farber Canc Inst, Dept Pharm & Clin Support, Boston, MA 02215 USA. [Salisbury, Mary] Cedar Inst Inc, San Antonio, TX USA. [Mann, Susan] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. RP Bunnell, CA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room D 1614, Boston, MA 02215 USA. EM craig_bunnell@dfci.harvard.edu FU Controlled Risk Insurance Company/Risk Management Foundation CRICO/RMF FX Controlled Risk Insurance Company/Risk Management Foundation CRICO/RMF provided funding for the physician/nurse consultant team that assisted us on this project. NR 23 TC 17 Z9 17 U1 2 U2 19 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD MAY PY 2013 VL 22 IS 5 SI SI BP 405 EP 413 DI 10.1136/bmjqs-2012-000948 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 130LD UT WOS:000317917400005 PM 23349386 ER PT J AU Heras, FL Martuza, R Caruso, P Rincon, S Stemmer-Rachamimov, A AF Heras, Facundo Las Martuza, Robert Caruso, Paul Rincon, Sandra Stemmer-Rachamimov, Anat TI 24-Year-Old Woman with An Internal Auditory Canal Mass Hybrid peripheral nerve sheath tumor with schwannoma/perineurioma components SO BRAIN PATHOLOGY LA English DT Editorial Material ID NEUROFIBROMA; PERINEURIOMA; SCHWANNOMA; CHALLENGE AB Benign peripheral nerve sheath tumors are divided into schwannomas, neurofibromas and perineuriomas. In recent years, tumors with hybrid features, composed of multiple, discrete areas of different histological types, were described. These tumors may represent a diagnostic challenge. A 24-year-old woman with multiple sclerosis was found to have a 1.3 cm TV 0.7 cm AP T2 intermediate lesion within the left internal auditory canal. Gross examination revealed a tan-white, well circumscribed mass. Histologic examination demonstrated a well demarcated, cellular, solid neoplasm with a biphasic pattern. Most of the tumor was composed of spindle cells arranged in fascicles with focal Verocay body formation and diffuse S100 positivity. A second, minor area showed concentric proliferation of neoplastic spindle cells around one or more axons. Tumor cells in this area were positive for perineurial markers, claudin-1 and Glut-1, and focally immunopositive for CD34. We present here a case of a benign peripheral nerve sheath tumor with histological and immunohistochemical features consistent with a dual pattern of differentiation of schwannoma and perineurioma, in the VIIIth cranial nerve. This is, to our knowledge, the first case of a hybrid perineurioma/schwannoma reported in a cranial nerve. C1 [Heras, Facundo Las] Univ Chile, Clin Hosp, Dept Anat Pathol, Santiago, Chile. [Martuza, Robert] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Caruso, Paul; Rincon, Sandra] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Heras, FL (reprint author), Univ Chile, Clin Hosp, Dept Anat Pathol, Santiago, Chile. NR 10 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD MAY PY 2013 VL 23 IS 3 BP 361 EP 362 DI 10.1111/bpa.12055 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 129TP UT WOS:000317865800016 ER PT J AU Schapira, L AF Schapira, Lidia TI The Essential Elements of a Therapeutic Presence SO CANCER LA English DT Editorial Material C1 [Schapira, Lidia] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YA 9, Boston, MA 02114 USA. EM lschapira@partners.org NR 3 TC 2 Z9 2 U1 0 U2 0 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 MAY 1 PY 2013 VL 119 IS 9 BP 1609 EP 1610 PG 2 WC Oncology SC Oncology GA 133CM UT WOS:000318115000002 PM 23341022 ER PT J AU Weber, JS Dummer, R de Pril, V Lebbe, C Hodi, FS AF Weber, Jeffrey S. Dummer, Reinhard de Pril, Veerle Lebbe, Celeste Hodi, F. Stephen CA MDX010-20 Investigators TI Patterns of Onset and Resolution of Immune-Related Adverse Events of Special Interest With Ipilimumab Detailed Safety Analysis From a Phase 3 Trial in Patients With Advanced Melanoma SO CANCER LA English DT Article DE adverse drug events; immune system phenomenon; ipilimumab; mechanism of action; metastatic melanoma ID T-CELLS; METASTATIC MELANOMA; GLUCOCORTICOIDS; ANTI-CTLA-4; MANAGEMENT AB BACKGROUND: Ipilimumab 3 mg/kg was the first agent to demonstrate improved survival in previously treated patients with metastatic melanoma in a phase 3 trial (MDX010-20). Ipilimumab produced a characteristic spectrum of immune-related adverse events (irAEs) of special interest, consistent with its immune-based mechanism of action. METHODS: In MDX010-20, 676 previously treated patients were randomized 3:1:1 to receive ipilimumab 3 mg/kg plus the glycoprotein 100 melanoma antigen vaccine (gp100), ipilimumab 3 mg/kg + placebo, or gp100 vaccine + placebo. For the current report, the authors conducted a detailed analysis of the time to onset and resolution of irAEs associated with ipilimumab therapy. RESULTS: Grade 2 through 5 irAEs generally developed during the induction phase of treatment (0-12 weeks). Most, including grade 3/4 irAEs, were reversible when managed with treatment guidelines using vigilant monitoring and corticosteroids. The median time to resolution (to grade 1 or 0 or to the grade at baseline) of irAEs that had an onset during the induction phase was approximately 6 weeks for grade 2 through 4 irAEs and 8 weeks for grade 3 and 4 irAEs. Across the entire study duration, most grade 2 through 4 irAEs resolved within 12 weeks. CONCLUSIONS: Most ipilimumab-associated irAEs, including grade 3/4 symptoms, developed within 12 weeks of initial dosing and resolved within 12 weeks of onset. IrAEs were well characterized in their evolution and could be managed using published algorithms. Cancer 2013; 119: 1675-82. (C) 2013 American Cancer Society. C1 [Weber, Jeffrey S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Donald A Adam Comprehens Melanoma Res Ctr, Tampa, FL 33612 USA. [Dummer, Reinhard] Univ Zurich, Dept Dermatol, Zurich, Switzerland. [de Pril, Veerle] Bristol Myers Squibb Co, Braine Lalleud, Belgium. [Lebbe, Celeste] Paris Publ Assistance Hosp Syst, Clin Invest Ctr, Paris, France. [Lebbe, Celeste] Hosp St Louis Fac, Dept Dermatol, Paris, France. [Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Ctr, Boston, MA 02115 USA. RP Weber, JS (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Donald A Adam Comprehens Melanoma Res Ctr, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM jeffrey.weber@moffitt.org FU AstraZeneca; Novartis; Cephalon; Merck; Transgene; Bristol-Myers Squibb [NCT00094653]; Roche; GlaxoSmithKline; Bayer FX The MDX010-20 trial (NCT00094653) was sponsored by Bristol-Myers Squibb. Editorial and writing assistance was provided by StemScientific, which was funded by Bristol-Myers Squibb.; J.S.W. has received honoraria from Bristol-Myers Squibb. R.D. has received research funding from and has served as an advisor for AstraZeneca, Novartis, Cephalon, Merck, Transgene, Bristol-Myers Squibb, Roche, GlaxoSmithKline, and Bayer, and he also has served as an advisor for Genta and Spirig Pharma. V.d.P. is an employee of Bristol-Myers Squibb. C.L. has received honoraria from Bristol-Myers Squibb. F.S.H. has served as a nonpaid consultant and has received clinical research support from Bristol-Myers Squibb. NR 20 TC 92 Z9 95 U1 4 U2 16 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 MAY 1 PY 2013 VL 119 IS 9 BP 1675 EP 1682 DI 10.1002/cncr.27969 PG 8 WC Oncology SC Oncology GA 133CM UT WOS:000318115000011 PM 23400564 ER PT J AU Gray, PJ Paly, JJ Yeap, BY Sanda, MG Sandler, HM Michalski, JM Talcott, JA Coen, JJ Hamstra, DA Shipley, WU Hahn, SM Zietman, AL Bekelman, JE Efstathiou, JA AF Gray, Phillip J. Paly, Jonathan J. Yeap, Beow Y. Sanda, Martin G. Sandler, Howard. M. Michalski, Jeff M. Talcott, James A. Coen, John J. Hamstra, Daniel A. Shipley, William U. Hahn, Stephen M. Zietman, Anthony L. Bekelman, Justin E. Efstathiou, Jason A. TI Patient-Reported Outcomes After 3-Dimensional Conformal, Intensity-Modulated, or Proton Beam Radiotherapy for Localized Prostate Cancer SO CANCER LA English DT Article DE 3-dimensional conformal radiotherapy; intensity-modulated radiotherapy; patient reported outcomes; prostate cancer; proton therapy; quality of life ID QUALITY-OF-LIFE; LATE RECTAL TOXICITY; RADIATION-THERAPY; BOWEL TOXICITY; TIME-COURSE; 3D-CRT; PREDICTORS; SYMPTOMS; ADENOCARCINOMA; INCONTINENCE AB BACKGROUND: Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam therapy (PBT). METHODS: The authors reviewed patient-reported outcomes data collected prospectively using validated instruments that assessed bowel and urinary quality of life (QOL) for patients with localized prostate cancer who received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful differences in mean QOL scores were defined as those exceeding half the standard deviation of the base-line mean value. Changes from baseline were compared within groups at the first post-treatment follow-up (2-3 months from the start of treatment) and at 12 months and 24 months. RESULTS: At the first post-treatment follow-up, patients who received 3DCRT and IMRT, but not those who received PBT, reported a clinically meaningful decrement in bowel QOL. At 12 months and 24 months, all 3 cohorts reported clinically meaningful decrements in bowel QOL. Patients who received IMRT reported clinically meaningful decrements in the domains of urinary irritation/obstruction and incontinence at the first post-treatment follow-up. At 12 months, patients who received PBT, but not those who received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary irritation/obstruction domain. At 24 months, none of the 3 cohorts reported clinically meaningful changes in urinary QOL. CONCLUSIONS: Patients who received 3DCRT, IMRT, or PBT reported distinct patterns of treatment-related QOL. Although the timing of toxicity varied between the cohorts, patients reported similar modest QOL decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months. Prospective randomized trials are needed to further examine these differences. Cancer 2013; 119: 1729-35. (C) 2013 American Cancer Society. C1 [Gray, Phillip J.] Harvard Radiat Oncol Program, Boston, MA USA. [Paly, Jonathan J.; Yeap, Beow Y.; Shipley, William U.; Zietman, Anthony L.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Div Urol Surg, Boston, MA 02215 USA. [Sandler, Howard. M.] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Michalski, Jeff M.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. [Talcott, James A.] Continuum Canc Care Consortium, New York, NY USA. [Coen, John J.] Hartford Radiat Oncol Associates, Hartford, CT USA. [Hamstra, Daniel A.] Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Hahn, Stephen M.; Bekelman, Justin E.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org RI Sanda, Martin/B-2023-2015 FU Federal Share of program income earned by Massachusetts General Hospital on Proton Therapy Research and Treatment Cente [C06 CA059267]; National Institutes of Health (NIH) [R01CA95662, 1RC1CA146596, K07CA163616]; University of Pennsylvania FX This work was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center, by National Institutes of Health (NIH) grants R01CA95662, 1RC1CA146596, and K07CA163616, and by internal funding from the University of Pennsylvania. NR 45 TC 36 Z9 36 U1 0 U2 14 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 MAY 1 PY 2013 VL 119 IS 9 BP 1729 EP 1735 DI 10.1002/cncr.27956 PG 7 WC Oncology SC Oncology GA 133CM UT WOS:000318115000018 PM 23436283 ER PT J AU Motiwala, SR Januzzi, JL AF Motiwala, Shweta R. Januzzi, James L., Jr. TI Using Biomarkers to "Guide" Heart Failure Management: Current Perspectives and Future Directions SO CARDIOLOGY IN REVIEW LA English DT Review DE heart failure; biomarker; natriuretic peptide; therapeutic target; outcomes ID BRAIN-NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT PRIDE; CARDIAC RESYNCHRONIZATION THERAPY; VENTRICULAR SYSTOLIC DYSFUNCTION; PROGNOSTIC VALUE; CARDIOVASCULAR EVENTS; ATRIAL-FIBRILLATION; LOOP DIURETICS; BNP; PROBNP AB Over the last several years, cardiac biomarkers have proven to be increasingly useful for disease screening, diagnosis, and prognostication. The most widely used biomarkers in heart failure (HF) are natriuretic peptides (NPs), which can aid in diagnosing HF, while also identifying those who are at higher risk of adverse outcomes. Multiple clinical trials have investigated the role of NPs as therapeutic targets for HF management, but results have been conflicting. Collectively, however, the data suggest that NP levels may be useful in guiding HF management and improving HF-related morbidity and mortality. In this review, we summarize existing data investigating the use of NPs as targets for outpatient HF therapy, focusing on differences in study designs and lessons learned from the results. Although the results for this approach are promising overall, we propose that additional well-designed prospective randomized controlled trials-specifically incorporating the relevant lessons learned from previous studies-are necessary to pivotally establish the role of NP-guided outpatient HF management. C1 [Motiwala, Shweta R.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Roche Diagnostics; Critical Diagnostics; Siemens; BRAHMS; BG Medicine FX Dr. Januzzi has received grant support from Roche Diagnostics, Critical Diagnostics, Siemens, BRAHMS, and BG Medicine. Dr. Motiwala declares no conflicts of interest. NR 42 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1061-5377 J9 CARDIOL REV JI Cardiol. Rev. PD MAY-JUN PY 2013 VL 21 IS 3 BP 127 EP 134 DI 10.1097/CRD.0b013e3182769073 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 126CT UT WOS:000317590000003 PM 23032578 ER PT J AU Shimada, M AF Shimada, Masako TI Overview of Calpain-Mediated Regulation of Bone and Fat Mass in Osteoblasts SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Calpain; Osteoblasts; Fat; Glucose metabolism; Cell cycle ID SYMPATHETIC-NERVOUS-SYSTEM; HORMONE-RELATED PEPTIDE; SMALL-SUBUNIT GENE; PARATHYROID-HORMONE; LEPTIN REGULATION; CELL-PROLIFERATION; TARGETED DELETION; ENERGY-METABOLISM; NUCLEAR EXPORT; DIFFERENTIATION AB The receptor for parathyroid hormone (PTH) and PTH-related peptide (PTH1R) belongs to the class II G protein-coupled receptor superfamily. The calpain small subunit encoded by the gene Capns1 is the second protein and the first enzyme identified by a yeast two-hybrid screen using the intracellular C-terminal tail of the rat PTH1R. The calpain regulatory small subunit forms a heterodimer with the calpain large catalytic subunit and modulates various cellular functions as a cysteine protease. To investigate a physiological role of the calpain small subunit in cells of the osteoblast lineage, we generated osteoblast-specific Capns1 knockout mouse models and characterized their bone phenotype. Molecular mechanisms by which calpain modulates cell proliferation of the osteoblast lineage were further examined in vitro. Moreover, we utilized the mutant mice as a disease model of osteoporosis accompanied with impaired bone resorptive function and suggested a possible clinical translation of our basic research finding. C1 [Shimada, Masako] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Shimada, Masako] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Shimada, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 10,50 Blossom St, Boston, MA 02114 USA. EM shimada@helix.mgh.harvard.edu FU National Institutes of Health [R01 DK072102, P30 DK057521]; William F. Milton Fund; MGH FX This work was partially supported by the National Institutes of Health grants R01 DK072102 and P30 DK057521, the William F. Milton Fund, and the MGH interim support fund (to M. S.). NR 35 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PD MAY PY 2013 VL 66 IS 1 BP 23 EP 28 DI 10.1007/s12013-012-9393-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 129RZ UT WOS:000317860900004 PM 22821549 ER PT J AU Cosentino, C Mostoslavsky, R AF Cosentino, Claudia Mostoslavsky, Raul TI Metabolism, longevity and epigenetics SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Acetylation; HDAC; Sirtuin; Aging; Metabolism; Senescence ID DNA-DAMAGE RESPONSE; ATP-CITRATE LYASE; HISTONE DEACETYLASE SIRT6; FATTY-ACID OXIDATION; CALORIE RESTRICTION; CELLULAR SENESCENCE; LIFE-SPAN; CAENORHABDITIS-ELEGANS; SKELETAL-MUSCLE; HUMAN-CELLS AB Metabolic homeostasis and interventions that influence nutrient uptake are well-established means to influence lifespan even in higher eukaryotes. Until recently, the molecular mechanisms explaining such an effect remained scantily understood. Sirtuins are a group of protein deacetylases that depend on the metabolic intermediate NAD(+) as a cofactor for their function. For this reason they sense metabolic stress and in turn function at multiple levels to exert proper metabolic adaptation. Among other things, sirtuins can perform as histone deacetylases inducing epigenetic changes to modulate transcription and DNA repair. Recent studies have indicated that beyond sirtuins, the activity of other chromatin modifiers, such as histone acetyl transferases, might also be tightly linked to the availability of their intermediate metabolite acetyl-CoA. We summarize current knowledge of the emerging concepts indicating close crosstalk between the epigenetic machineries able to sense metabolic stress, their adaptive metabolic responses and their potential role in longevity. C1 [Cosentino, Claudia; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 185 Cambridge St, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu FU NCI NIH HHS [R01 CA175727]; NIDDK NIH HHS [R01 DK088190]; NIGMS NIH HHS [R01 GM093072] NR 148 TC 16 Z9 18 U1 4 U2 55 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAY PY 2013 VL 70 IS 9 BP 1525 EP 1541 DI 10.1007/s00018-013-1295-3 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 126OE UT WOS:000317626400004 PM 23467663 ER PT J AU Patti, ME AF Patti, Mary-Elizabeth TI Intergenerational programming of metabolic disease: evidence from human populations and experimental animal models SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Intergenerational; Metabolic disease; Epigenetics ID HIGH-FAT DIET; LOW-BIRTH-WEIGHT; TRANSGENERATIONAL EPIGENETIC INHERITANCE; SLOW GROWTH PERIOD; IN-UTERO EXPOSURE; DNA METHYLATION; CAENORHABDITIS-ELEGANS; C. ELEGANS; GLUCOSE-INTOLERANCE; GENE-EXPRESSION AB We are in the midst of unparalleled epidemics of obesity and type 2 diabetes-complex phenotypes originating at the intersection of genetic and environmental risk. As detailed in other chapters, evidence indicates that non-genetic, or environmental, risk may initiate during prenatal and early postnatal life [1]. Striking examples in humans include the association of low birth weight (LBW) and/or accelerated early growth with increased risk of insulin resistance, obesity, type 2 diabetes (T2DM), and cardiovascular disease (CVD), and the close relationship between maternal obesity or diabetes with childhood obesity. In this chapter, we will focus on the intriguing emerging data from both human and animal models that indicate that intrauterine and childhood exposures can also influence risk for diabetes and cardiovascular disease in subsequent generations. Understanding the mechanisms responsible for these effects is critical in order to develop effective metabolic and nutritional interventions to interrupt such vicious intergenerational cycles potentiating risk for metabolic disorders. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Patti, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836] NR 111 TC 28 Z9 28 U1 4 U2 39 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAY PY 2013 VL 70 IS 9 BP 1597 EP 1608 DI 10.1007/s00018-013-1298-0 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 126OE UT WOS:000317626400007 PM 23435955 ER PT J AU Smith, MJ Esparza, S Merker, VL Muzikansky, A Bredella, MA Harris, GJ Kassarjian, A Cai, WL Walker, JA Mautner, VF Plotkin, SR AF Smith, Miriam J. Esparza, Sonia Merker, Vanessa L. Muzikansky, Alona Bredella, Miriam A. Harris, Gordon J. Kassarjian, Ara Cai, Wenli Walker, James A. Mautner, Victor F. Plotkin, Scott R. TI Plasma S100 beta is not a useful biomarker for tumor burden in neurofibromatosis SO CLINICAL BIOCHEMISTRY LA English DT Article DE S100 beta; Neurofibroma; Schwannoma; Biomarker; Neurofibromatosis ID BRAIN; TYPE-1; GENE AB Objectives: Neurofibromatosis 1 (NF1), NF2, and schwannomatosis are characterized by a predisposition to develop multiple neurofibromas and schwannomas. Currently, there is no blood test to estimate tumor burden in patients with these disorders. We explored whether S100 beta would act as a biomarker of tumor burden in NF since S100 beta is a classic immunohistochemical marker of astrocytes, oligodendrocytes and Schwann cells and a small study showed S100 beta concentrations correlate with the volume of vestibular schwannomas. Design and methods: We calculated whole-body tumor burden in subjects with NF1, NF2, and schwannomatosis using whole-body MRI (WBMRI) and measured the concentration of Sloop in plasma using ELISA. We used chi-square tests and Spearman rank correlations to test the relationship between S100 beta levels and whole-body tumor burden. Results: 127 consecutive patients were enrolled in the study (69 NF1 patients, 28 NF2 patients, and 30 schwannomatosis patients). The median age was 40 years, 43% were male, and median whole-body tumor volume was 26.9 mL. There was no relationship between the presence of internal tumors and the presence of detectable S100 beta in blood for the overall group or for individual diagnoses (p>0.05 by chi-square for all comparisons). Similarly, there was no correlation between whole-body tumor volume and S100 beta concentration for the overall group or for individual diagnoses (p>0.05 by Spearman for all comparisons). Conclusions: Plasma S100 beta is not a useful biomarker for tumor burden in the neurofibromatoses. Further work is needed to identify a reliable biomarker of tumor burden in NF patients. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Smith, Miriam J.; Esparza, Sonia; Merker, Vanessa L.; Walker, James A.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Esparza, Sonia; Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Bredella, Miriam A.; Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kassarjian, Ara] Corades SL, Dept Radiol, Majadahonda, Spain. [Walker, James A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mautner, Victor F.] Univ Hamburg Hosp, Dept Neurol, Hamburg, Germany. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org RI Smith, Miriam/J-4001-2015 OI Smith, Miriam/0000-0002-3184-0817 FU DOD [NF050202]; Center for Neurofibromatosis and Allied Disorders FX Support for this project was provided by DOD NF050202 (SRP) and by the Center for Neurofibromatosis and Allied Disorders. The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. NR 11 TC 2 Z9 2 U1 0 U2 6 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 MAY PY 2013 VL 46 IS 7-8 BP 698 EP 700 DI 10.1016/j.clinbiochem.2012.12.007 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 129XU UT WOS:000317878100026 PM 23261835 ER PT J AU Cuenca, AG Gentile, LF Lopez, MC Ungaro, R Liu, HZ Xiao, WZ Seok, J Mindrinos, MN Ang, D Baslanti, TO Bihorac, A Efron, PA Cuschieri, J Warren, HS Tompkins, RG Maier, RV Baker, HV Moldawer, LL AF Cuenca, Alex G. Gentile, Lori F. Lopez, M. Cecilia Ungaro, Ricardo Liu, Huazhi Xiao, Wenzhong Seok, Junhee Mindrinos, Michael N. Ang, Darwin Baslanti, Tezcan Ozrazgat Bihorac, Azra Efron, Philip A. Cuschieri, Joseph Warren, H. Shaw Tompkins, Ronald G. Maier, Ronald V. Baker, Henry V. Moldawer, Lyle L. CA Inflammation Host Response Injury TI Development of a Genomic Metric That Can Be Rapidly Used to Predict Clinical Outcome in Severely Injured Trauma Patients SO CRITICAL CARE MEDICINE LA English DT Article DE blunt trauma; genomic composite score; microarray; validation ID CONTROLLED MULTICENTER TRIAL; RECEPTOR FUSION PROTEIN; MULTIPLE ORGAN FAILURE; GENE-EXPRESSION; SEVERE SEPSIS; HOSPITAL DEATHS; SEPTIC SHOCK; LOCATION; PATTERN; TIME AB Objective: Many patients have complicated recoveries following severe trauma due to the development of organ injury. Physiological and anatomical prognosticators have had limited success in predicting clinical trajectories. We report on the development and retrospective validation of a simple genomic composite score that can be rapidly used to predict clinical outcomes. Design: Retrospective cohort study. Setting: Multi-institutional level 1 trauma centers. Patients: Data were collected from 167 severely traumatized (injury severity score >15) adult (18-55 yr) patients. Methods: Microarray-derived genomic data obtained from 167 severely traumatized patients over 28 days were assessed for differences in messenger RNA abundance among individuals with different clinical trajectories. Once a set of genes was identified based on differences in expression over the entire study period, messenger RNA abundance from these subjects obtained in the first 24 hours was analyzed in a blinded fashion using a rapid multiplex platform, and genomic data reduced to a single metric. Results: From the existing genomic dataset, we identified 63 genes whose leukocyte expression differed between an uncomplicated and complicated clinical outcome over 28 days. Using a multiplex approach that can quantitate messenger RNA abundance in less than 12 hours, we reassessed total messenger RNA abundance from the first 24 hours after trauma and reduced the genomic data to a single composite score using the difference from reference. This composite score showed good discriminatory capacity to distinguish patients with a complicated outcome (area under a receiver-operator curve, 0.811; p <0.001). This was significantly better than the predictive power of either Acute Physiology and Chronic Health Evaluation II or new injury severity score scoring systems. Conclusions: A rapid genomic composite score obtained in the first 24 hours after trauma can retrospectively identify trauma patients who are likely to develop complicated clinical trajectories. A novel platform is described in which this genomic score can be obtained within 12 hours of blood collection, making it available for clinical decision making. (Crit Care Med 2013; 41:1175-1185) C1 [Cuenca, Alex G.; Gentile, Lori F.; Ungaro, Ricardo; Liu, Huazhi; Ang, Darwin; Efron, Philip A.; Baker, Henry V.; Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32611 USA. [Lopez, M. Cecilia; Baker, Henry V.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Xiao, Wenzhong; Seok, Junhee; Mindrinos, Michael N.] Stanford Genome Technol Ctr, Palo Alto, CA USA. [Baslanti, Tezcan Ozrazgat; Bihorac, Azra] Univ Florida, Coll Med, Dept Anesthesiol, Gainesville, FL USA. [Cuschieri, Joseph; Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Warren, H. Shaw] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Moldawer, LL (reprint author), Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32611 USA. EM moldawer@surgery.ufl.edu RI Bihorac, Azra/Q-6500-2016; OI Bihorac, Azra/0000-0002-5745-2863; Baker, Henry/0000-0002-8273-5320; xiao, wenzhong/0000-0003-4944-6380 FU National Institute of General Medical Sciences [K23 GM-087709-03]; T32 training grant in burns and trauma from the National Institutes of General Medical Sciences [T32 GM-008721-13]; National Research Service Award [F32 GM-093665-01]; National Institutes of General Medical Sciences, U.S. Public Health Service; [U54 GM-062119-10] FX This work was supported, in part, by a contract (U54 GM-062119-10) awarded by the National Institute of General Medical Sciences. Drs. Cuenca and Gentile were supported by a T32 training grant (T32 GM-008721-13) in burns and trauma from the National Institutes of General Medical Sciences. Dr. Cuenca was also supported by an individual National Research Service Award (F32 GM-093665-01) awarded by the National Institutes of General Medical Sciences, U.S. Public Health Service. Dr. Bihorac was supported by an award (K23 GM-087709-03) from the National Institute of General Medical Sciences. NR 29 TC 25 Z9 26 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2013 VL 41 IS 5 BP 1175 EP 1185 DI 10.1097/CCM.0b013e318277131c PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 126ZB UT WOS:000317661000020 PM 23388514 ER PT J AU Herring, AA Ginde, AA Fahimi, J Alter, HJ Maselli, JH Espinola, JA Sullivan, AF Camargo, CA AF Herring, Andrew A. Ginde, Adit A. Fahimi, Jahan Alter, Harrison J. Maselli, Judith H. Espinola, Janice A. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Increasing Critical Care Admissions From U.S. Emergency Departments, 2001-2009 SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine (SAEM) CY JUN 01-06, 2011 CL Boston, MA SP Soc Acad Emergency Med (SAEM) DE critical care; crowding; emergency service; health care disparities; hospital/workforce ID LENGTH-OF-STAY; UNITED-STATES; PATIENT MORTALITY; SEVERE SEPSIS; ILL PATIENTS; BED NUMBERS; TRENDS; COSTS; ASSOCIATION; OCCUPANCY AB Objectives: Little is known about how recent system-wide increases in demand for critical care have affected U.S. emergency departments (EDs). This study describes changes in the amount of critical care provided in U.S. EDs between 2001 and 2009. Design: Analysis of data from the National Hospital Ambulatory Medical Care Survey for the years 2001-2009. Setting: National multistage probability sample of U.S. ED data. U.S. ED capacity was estimated using the National Emergency Department Inventory-United States. Patients: ED patients admitted a critical care unit. Interventions: None. Measurements: Annual hours of ED-based critical care and annual number critical care ED visits. Clinical characteristics, demographics, insurance status, setting, geographic region, and ED length of stay for critically ill ED patients. Main Results: Annual critical care unit admissions from U.S. EDs increased by 79% from 1.2 to 2.2 million. The proportion of all ED visits resulting in critical care unit admission increased from 0.9% to 1.6% (p(trend) < 0.001). Between 2001 and 2009, the median ED length of stay for critically ill patients increased from 185 to 245 minutes (+ 60 min; p(trend) < 0.02). For the aggregated years 2001-2009, ED length of stay for critical care visits was longer among black patients (12.6% longer) and Hispanic patients (14.8% longer) than among white patients, and one third of all critical care ED visits had an ED length of stay greater than 6 hrs. Between 2001 and 2009, total annual hours of critical care at U.S. EDs increased by 217% from 3.2 to 10.1 million (p(trend) < 0.001). The average daily amount of critical care provided in U.S. EDs tripled from 1.8 to 5.6 hours per ED per day. Conclusions: The amount of critical care provided in U.S. EDs has increased substantially over the past decade, driven by increasing numbers of critical care ED visits and lengthening ED length of stay. Increased critical care burden will further stress an already overcapacity U.S. emergency care system. (Crit Care Med 2013; 41:1197-1204) C1 [Herring, Andrew A.; Fahimi, Jahan; Alter, Harrison J.] Highland Hosp, Alameda Cty Med Ctr, Dept Emergency Med, Oakland, CA USA. [Ginde, Adit A.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Maselli, Judith H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Espinola, Janice A.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Herring, AA (reprint author), Highland Hosp, Alameda Cty Med Ctr, Dept Emergency Med, Oakland, CA USA. EM aherring@acmedctr.org RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017 FU NIA NIH HHS [K23 AG040708] NR 36 TC 27 Z9 27 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2013 VL 41 IS 5 BP 1197 EP 1204 DI 10.1097/CCM.0b013e31827c086f PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 126ZB UT WOS:000317661000022 PM 23591207 ER PT J AU Schell, JO O'Hare, AM AF Schell, Jane O. O'Hare, Ann M. TI Illness trajectories and their relevance to the care of adults with kidney disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE communication; experience of illness; kidney disease; patient-centered; trajectory ID STAGE RENAL-DISEASE; LONG-TERM DIALYSIS; DECISION-MAKING; LAST YEAR; OF-LIFE; FUNCTIONAL DECLINE; CANCER-PATIENTS; OLDER-ADULTS; END; OUTCOMES AB Purpose of review Existing practice guidelines for chronic kidney disease advocate a stage-based approach to management, in which treatment recommendations are based largely on the severity of kidney disease, and future risk for adverse health outcomes. However, the course of kidney disease can vary widely among patients with similar levels of kidney function, and each patient will experience their illness in unique ways. Recent findings We summarize recent studies of patterns of kidney function over time among patients with chronic kidney disease, and discuss these findings in the context of relevant conceptual models of illness and communication. Although knowledge of disease severity can provide useful information on life expectancy and risk for future health events, an understanding of each patient's illness trajectory and their unique experience of illness is essential in supporting patient-centered care for patients with kidney disease. This information can be helpful in setting realistic expectations for the future, in communicating about prognosis and in aligning treatment decisions with each patient's goals and preferences. Summary We here explain how an understanding of illness trajectories may be useful in predicting and guiding care and decision-making in patients with kidney disease. We highlight the importance of competing disease trajectories, the heterogeneity in renal function trajectories among patients with kidney disease, and the variability in these trajectories over time in individual patients. We discuss how individual disease trajectories can shape each patient's experience of illness. Finally, we explain how an understanding of an individual patient's illness trajectory and experience of illness may be useful in guiding discussions about prognosis and treatment decisions and in supporting a patient-centered approach to care. C1 [Schell, Jane O.] Univ Pittsburgh, Sch Med, Sect Palliat Care & Med Eth, UPMC, Pittsburgh, PA USA. [Schell, Jane O.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, UPMC, Pittsburgh, PA USA. [O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Dept Med, Seattle, WA USA. [O'Hare, Ann M.] Univ Washington, Seattle, WA 98195 USA. RP Schell, JO (reprint author), UPMC Montefiore, Suite 933W,200 Lothrop St, Pittsburgh, PA 15213 USA. EM schelljo@upmc.edu FU National Institute on Aging; Centers for Disease Control; Department of Veterans Affairs FX A.M.O. receives research funding from the National Institute on Aging, the Centers for Disease Control and the Department of Veterans Affairs and royalties from UpToDate. These funding sources had no role in this work. J.O.S. has no conflicts of interest to declare. NR 45 TC 9 Z9 9 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2013 VL 22 IS 3 BP 316 EP 324 DI 10.1097/MNH.0b013e32835ffaaf PG 9 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 126YK UT WOS:000317658800010 PM 23518464 ER PT J AU Platt, MY DeLelys, ME Preffer, FI Sohani, AR AF Platt, Mia Y. DeLelys, Michelle E. Preffer, Frederic I. Sohani, Aliyah R. TI Flow cytometry is of limited utility in the early identification of "Double-hit" B-cell lymphomas SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE flow cytometry; double-hit lymphoma; MYC; BCL2; BCL6; CD20; CD19 ID EXPRESSION; MYC; IMMUNOPHENOTYPE; FEATURES AB Background: B-cell lymphomas with concurrent translocations of MYC and BCL2 or BCL6, also known as double-hit lymphomas (DHL), are rare malignancies characterized by aggressive clinical behavior and poor prognosis. Previous reports suggest that decreased CD20 and/or CD19 expression by flow cytometry is relatively common in DHL and may help to identify cases requiring additional cytogenetic analysis. Methods: We conducted a retrospective analysis of 26 cases of DHL, and compared their flow cytometric characteristics to cases of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Cases were analyzed by four-color flow cytometry, and bivariate dot-plots were reviewed for light scatter characteristics, CD19, CD20, CD45, and surface light chain. Results: Relatively few DHL cases showed dim expression of CD19 or CD20, and statistically significant differences were found only in the frequency of dim CD19 expression between DHL and BL or DLBCL. Although concomitant dim CD19 and CD20 expression was exclusive to DHL, it was present in only a minority of cases. Conclusions: We conclude that although a subset of DHL expresses aberrant levels of CD19 and/or CD20 by flow cytometry, these findings are of limited utility in identifying cases requiring cytogenetic analysis due to their low frequency. Until more sensitive pathologic parameters can be identified and validated, the decision to perform cytogenetic analysis should rest on a combination of clinical, morphologic, and immunophenotypic features suggestive of high-grade, aggressive disease. (c) 2013 International Clinical Cytometry Society C1 [Platt, Mia Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Platt, MY (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ 245, Boston, MA 02114 USA. EM myplatt@partners.org NR 14 TC 12 Z9 12 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAY PY 2013 VL 84B IS 3 BP 143 EP 148 DI 10.1002/cyto.b.21076 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 132BE UT WOS:000318041900003 PM 23341189 ER PT J AU Nevis, K Obregon, P Walsh, C Guner-Ataman, B Burns, CG Burns, CE AF Nevis, Kathleen Obregon, Pablo Walsh, Conor Guner-Ataman, Burcu Burns, C. Geoffrey Burns, Caroline E. TI Tbx1 is Required for Second Heart Field Proliferation in Zebrafish SO DEVELOPMENTAL DYNAMICS LA English DT Article DE tbx1; zebrafish; heart; second heart field; cardiac ID SYNDROME CANDIDATE GENE; BRANCHIAL ARCH MUTANTS; CARDIAC OUTFLOW TRACT; PHARYNGEAL ARCH; CARDIOVASCULAR DEVELOPMENT; CARDIOMYOCYTE DIFFERENTIATION; DELETION SYNDROME; DISTINCT PHASES; EXPRESSION; GROWTH AB Background: The mammalian outflow tract (OFT) and primitive right ventricle arise by accretion of newly differentiated cells to the arterial pole of the heart tube from multi-potent progenitor cells of the second heart field (SHF). While mounting evidence suggests that the genetic pathways regulating SHF development are highly conserved in zebrafish, this topic remains an active area of investigation. Results: Here, we extend previous observations demonstrating that zebrafish tbx1 (van gogh, vgo) mutants show ventricular and OFT defects consistent with a conserved role in SHF-mediated cardiogenesis. Surprisingly, we reveal through double in situ analyses that tbx1 transcripts are excluded from cardiac progenitor cells and differentiated cardiomyocytes, suggesting a non-autonomous role in SHF development. Further, we find that the diminutive ventricle in vgo animals results from a 25% decrease in cardiomyocyte number that occurs subsequent to heart tube stages. Lastly, we report that although SHF progenitors are specified in the absence of Tbx1, they fail to be maintained due to compromised SHF progenitor cell proliferation. Conclusions: These studies highlight conservation of Tbx1 function in zebrafish SHF biology. Developmental Dynamics 242:550-559, 2013. (C) 2013 Wiley Periodicals, Inc. C1 [Nevis, Kathleen; Obregon, Pablo; Walsh, Conor; Guner-Ataman, Burcu; Burns, C. Geoffrey; Burns, Caroline E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Nevis, Kathleen; Obregon, Pablo; Walsh, Conor; Guner-Ataman, Burcu; Burns, C. Geoffrey; Burns, Caroline E.] Harvard Univ, Sch Med, Boston, MA USA. [Burns, C. Geoffrey; Burns, Caroline E.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Burns, CG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM gburns@cvrc.mgh.harvard.edu; cburns6@partners.org FU National Institutes of Health [5F32HL110627, 5R01HL096816, 5R01HL111179]; American Heart Association [10POST4170037, 10GRNT4270021]; Harvard Stem Cell Institute; March of Dimes Foundation [1-FY12-467]; National Heart Lung and Blood Institute [5R01HL-096816] FX Grant sponsor: National Institutes of Health; Grant numbers: 5F32HL110627; 5R01HL096816; 5R01HL111179; Grant sponsor: American Heart Association; Grant numbers: 10POST4170037, 10GRNT4270021; Grant sponsor: Harvard Stem Cell Institute; Grant sponsor: March of Dimes Foundation; Grant number: 1-FY12-467.; We thank L. Zon and I. Scott for providing zebrafish strains; J Holzschuh for providing a detailed Click-iT EdU labeling protocol; Fred Keeley for providing Elastin2 anti-serum; and the Developmental Studies Hybridoma Bank under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242, for providing the MF20 antibody. This work was supported by awards from the National Institutes of Health to K.N. (5F32HL110627); the American Heart Association to B. G-A. (10POST4170037); the American Heart Association (Grant in Aid no. 10GRNT4270021); the Harvard Stem Cell Institute (Seed Grant), and the National Heart Lung and Blood Institute (5R01HL-096816) to C. G. B; and the Harvard Stem Cell Institute (Young Investigator Award and Cardiovascular Program Award), National Heart Lung and Blood Institute (5R01HL111179), and the March of Dimes Foundation (1-FY12-467) to C. E. B. NR 49 TC 10 Z9 10 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2013 VL 242 IS 5 BP 550 EP 559 DI 10.1002/dvdy.23928 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 131PG UT WOS:000318005000012 PM 23335360 ER PT J AU Hollebecque, A Postel-Vinay, S Verweij, J Demetri, GD Flaherty, K Bedard, P Soria, JC AF Hollebecque, Antoine Postel-Vinay, Sophie Verweij, Jaap Demetri, George D. Flaherty, Keith Bedard, Philippe Soria, Jean-Charles TI Modifying phase I methodology to facilitate enrolment of molecularly selected patients SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Drug development; Trial methodology; Clinical trials; Phase I studies ID ADVERSE DRUG-REACTIONS; CELL LUNG-CANCER; PERSONALIZED MEDICINE; SURVIVAL; TUMORS; SCALE; VEMURAFENIB; PERFORMANCE; INHIBITION; CHALLENGES AB Over the last decade, the focus of anticancer drug development has shifted from empirical cytotoxic chemotherapy to mechanism-defined molecularly targeted agents, for which appropriate patient selection at the earliest possible point in drug development is rational and critical to success. With the recently legislated "breakthrough product" definition in the U. S., it may be possible to plan a single trial for registration purposes to confirm a major clinical effect observed in phase I. However, most phase I trial designs remain excessively conservative and are driven by criteria developed for cytotoxic agents with the goal of identifying a "maximum tolerable dose" with acceptable risks to patients. This focus on empiric "most dose with acceptable risk" may be misguided for mechanism-targeting new agents, and this could lead to unnecessary delays, increased costs and even higher risk of missing important signals of activity and benefit. There is a compelling need to modify phase I trial designs to facilitate enrichment in molecularly selected patients who are the most likely to harbour disease driven by the targeted pathway and to avoid unjustified exclusions based on obsolete criteria so that the right subset of patients can participate. After discussion of the main inconsistencies of current phase I designs, we propose a new strategy to facilitate the inclusion of molecularly selected patients, in order to accelerate and mitigate risks in drug development as well as to increase the chance of benefit among trial participants. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hollebecque, Antoine; Postel-Vinay, Sophie; Soria, Jean-Charles] Univ Paris 11, SITEP, Inst Gustave Roussy, Villejuif, France. [Verweij, Jaap] Erasmus Univ, Dept Med Oncol, Med Ctr, Dr Daniel Den Hoed Canc Ctr, NL-3075 EA Rotterdam, Netherlands. [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr Cell Signaling & Clin Discovery, Boston, MA 02215 USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Bedard, Philippe] Univ Toronto, Dept Med, Princess Margaret Hosp, Univ Hlth Network,Div Med Oncol & Hematol, Toronto, ON, Canada. RP Soria, JC (reprint author), Inst Gustave Roussy, SITEP, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM soria@igr.fr RI Hollebecque, Antoine/M-2695-2013 OI Hollebecque, Antoine/0000-0003-2869-7551 NR 27 TC 8 Z9 8 U1 0 U2 6 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 MAY PY 2013 VL 49 IS 7 BP 1515 EP 1520 DI 10.1016/j.ejca.2012.12.012 PG 6 WC Oncology SC Oncology GA 125TG UT WOS:000317563600001 PM 23333057 ER PT J AU Sharma, S Zhu, L Davoodi, M Harris-White, M Lee, JM St John, M Salgia, R Dubinett, S AF Sharma, Sherven Zhu, Li Davoodi, Michael Harris-White, Marni Lee, Jay M. St John, Maie Salgia, Ravi Dubinett, Steven TI TLR3 agonists and proinflammatory antitumor activities SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Editorial Material DE cancer; immune suppression; immune therapy; TLR3 agonists ID TOLL-LIKE RECEPTOR-3; POLYRIBOINOSINIC-POLYRIBOCYTIDYLIC ACID; POLYINOSINIC-POLYCYTIDYLIC ACID; CANCER-CELLS; DENDRITIC CELLS; I INTERFERONS; APOPTOSIS; TRIAL AB Although tumor growth leads to inflammatory responses, the immune system develops tolerance to cancer. One way to break host tolerance to tumors is to activate key immune effector activities. Toward this end, various adjuvants are under investigation in an effort to harness the immune system to overcome tolerance to tumor-associated self-antigens. There is enthusiasm for the use of specific ligands for toll-like receptor 3 (TLR3) that play a key role in the innate immune system. TLR3 agonists serve as immune adjuvants because they potently induce innate immune responses by activating dendritic cell ( DC) maturation and inflammatory cytokine secretion. These activities facilitate the bridge between the innate and adaptive immune systems promoting the expansion of cytotoxic T lymphocytes (CTL) that destroy cancer cells. TLR3 agonists either alone or in combination with tumor antigens have shown success in terms of enhancing immune responses and eliciting antitumor activity in preclinical models. However, TLR3 agonists can also impact regulatory cells that dampen immune responses. Thus, immune strategies that utilize TLR3 agonists should consider the relative induction of suppressive as well as beneficial antitumor immune activities. Herein, we summarize the TLR3 agonists that will hopefully come to clinical fruition. C1 [Sharma, Sherven; Zhu, Li; Davoodi, Michael; Lee, Jay M.; St John, Maie; Dubinett, Steven] Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Lung Canc Res Program, Los Angeles, CA 90024 USA. [Sharma, Sherven; Lee, Jay M.; St John, Maie; Dubinett, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Sharma, Sherven; Zhu, Li; Davoodi, Michael; Harris-White, Marni; Dubinett, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA USA. [Salgia, Ravi] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Lung Canc Program,Div Pulm & Crit Care Med,Mol Ge, Los Angeles, CA 90024 USA. EM ssharma@mednet.ucla.edu FU NCATS NIH HHS [UL1 TR000124, UL1TR000124]; NCI NIH HHS [R01 CA085686, P50 CA090388, P50 CA90388, R01 CA126944, R01 CA95686]; NIDCR NIH HHS [K23 DE021193] NR 17 TC 6 Z9 6 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD MAY PY 2013 VL 17 IS 5 BP 481 EP 483 DI 10.1517/14728222.2013.781585 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 130RA UT WOS:000317935400002 PM 23506058 ER PT J AU Wu, MX Ustyugova, IV Han, LP Akilov, OE AF Wu, Mei X. Ustyugova, Irina V. Han, Liping Akilov, Oleg E. TI Immediate early response gene X-1, a potential prognostic biomarker in cancers SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE apoptosis; biomarkers; cancer prognosis; IF1; immediate early response gene X-1 ID NF-KAPPA-B; MULTIPLE-MYELOMA CELLS; UP-REGULATION; MYELODYSPLASTIC SYNDROME; PANCREATIC-CANCER; INDUCED APOPTOSIS; BONE-MARROW; F1FO-ATPASE INHIBITOR; IEX-1 EXPRESSION; CARCINOMA CELLS AB Introduction: The immediate early response gene X-1 (IEX-1) plays a pivotal role in the regulation of cell apoptosis, proliferation, differentiation and metabolism. Deregulation of IEX-1 expression has been confirmed in multiple cancers in humans, in association with either poor or better prognosis depending on the type and progression stages of the cancer. Areas covered: This review summarizes clinical studies of altered IEX-1 expression in ovarian, pancreatic, blood, breast and colorectal cancers, lymphoma and myeloma. The authors also outline the current understandings of the complex functions of IEX-1 gained from studies with animal models and tumor cell lines so as to help us comprehend the significance of the clinical findings. Expert opinion: IEX-1 holds great promise to be a valuable biomarker, either alone or in combination with other genes, for monitoring progression of some cancers. IEX-1 expression is highly sensitive to environmental cues and distinct between normal and cancer cells. However, use of IEX-1 as a biomarker remains a significant challenge because too little is understood about the mechanism underlying the diverse activities of IEX-1 and a standardized clinical assay for IEX-1 detection and validation of clinical results across different studies are still critically lacking. C1 [Wu, Mei X.; Ustyugova, Irina V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wu, Mei X.; Ustyugova, Irina V.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Dept Dermatol, Boston, MA 02114 USA. [Han, Liping] Henan Univ, Affiliated Hosp 1, Dept Obstet & Gynaecol, Zhengzhou, Peoples R China. [Akilov, Oleg E.] Univ Pittsburgh, Med Ctr, Dept Dermatol, Pittsburgh, PA 15213 USA. [Ustyugova, Irina V.] Sanofi Pasteur Biol Co, Cambridge, MA 02139 USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org FU National Institutes of Health (NIH) [AI050822, CA158756, AI070785]; Senior Research Award from the Crohn's & Colitis Foundation of America FX This work is supported in part by National Institutes of Health (NIH) grants AI050822, CA158756 and AI070785 and a Senior Research Award from the Crohn's & Colitis Foundation of America (to M.X.W.). NR 79 TC 9 Z9 9 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD MAY PY 2013 VL 17 IS 5 BP 593 EP 606 DI 10.1517/14728222.2013.768234 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 130RA UT WOS:000317935400011 PM 23379921 ER PT J AU Kashyap, PC Marcobal, A Ursell, LK Larauche, M Duboc, H Earle, KA Sonnenburg, ED Ferreyra, JA Higginbottom, SK Million, M Tache, Y Pasricha, PJ Knight, R Farrugia, G Sonnenburg, JL AF Kashyap, Purna C. Marcobal, Angela Ursell, Luke K. Larauche, Muriel Duboc, Henri Earle, Kristen A. Sonnenburg, Erica D. Ferreyra, Jessica A. Higginbottom, Steven K. Million, Mulugeta Tache, Yvette Pasricha, Pankaj J. Knight, Rob Farrugia, Gianrico Sonnenburg, Justin L. TI Complex Interactions Among Diet, Gastrointestinal Transit, and Gut Microbiota in Humanized Mice SO GASTROENTEROLOGY LA English DT Article DE Dietary Carbohydrates; Microbiome; Metabolomics; Serotonin ID INTESTINE; HEALTH; INFLAMMATION; DISORDERS; SEROTONIN; BACTERIA; DISEASE; SYSTEM; TRACT; FIBER AB BACKGROUND & AIMS: Diet has major effects on the intestinal microbiota, but the exact mechanisms that alter complex microbial communities have been difficult to elucidate. In addition to the direct influence that diet exerts on microbes, changes in microbiota composition and function can alter host functions such as gastrointestinal (GI) transit time, which in turn can further affect the microbiota. METHODS: We investigated the relationships among diet, GI motility, and the intestinal microbiota using mice that are germ-free (GF) or humanized (ex-GF mice colonized with human fecal microbiota). RESULTS: Analysis of gut motility revealed that humanized mice fed a standard polysaccharide-rich diet had faster GI transit and increased colonic contractility compared with GF mice. Humanized mice with faster transit due to administration of polyethylene glycol or a nonfermentable cellulose-based diet had similar changes in gut microbiota composition, indicating that diet can modify GI transit, which then affects the composition of the microbial community. However, altered transit in mice fed a diet of fermentable fructooligosaccharide indicates that diet can change gut microbial function, which can affect GI transit. CONCLUSIONS: Based on studies in humanized mice, diet can affect GI transit through microbiota-dependent or microbiota-independent pathways, depending on the type of dietary change. The effect of the microbiota on transit largely depends on the amount and type (fermentable vs nonfermentable) of polysaccharides present in the diet. These results have implications for disorders that affect GI transit and gut microbial communities, including irritable bowel syndrome and inflammatory bowel disease. C1 [Kashyap, Purna C.; Marcobal, Angela; Earle, Kristen A.; Sonnenburg, Erica D.; Ferreyra, Jessica A.; Higginbottom, Steven K.; Sonnenburg, Justin L.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Pasricha, Pankaj J.] Stanford Univ, Sch Med, Dept Gastroenterol & Hepatol, Stanford, CA 94305 USA. [Kashyap, Purna C.; Farrugia, Gianrico] Mayo Clin, Dept Gastroenterol & Hepatol, Rochester, MN USA. [Ursell, Luke K.; Million, Mulugeta; Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Larauche, Muriel; Duboc, Henri; Tache, Yvette] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Larauche, Muriel; Duboc, Henri; Tache, Yvette] Univ Calif Los Angeles, Div Digest Dis, Ctr Neurobiol Stress, Los Angeles, CA USA. [Larauche, Muriel; Duboc, Henri; Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. RP Sonnenburg, JL (reprint author), Stanford Univ, Sch Med, Dept Microbiol & Immunol, 299 Campus Dr,Fairchild Bldg D315, Stanford, CA 94305 USA. EM jsonnenburg@stanford.edu RI Knight, Rob/D-1299-2010; OI Larauche, Muriel/0000-0003-3320-3675 FU National Institutes of Health [R01DK085025]; Digestive Diseases Center [DK-41301, K01 DK088937] FX Supported by National Institutes of Health grant R01DK085025 (to J.L.S.), Digestive Diseases Center grant DK-41301 (Animal Models Core; to Y.T., M. M.) and K01 DK088937 (M.L.). NR 32 TC 88 Z9 90 U1 14 U2 124 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 MAY PY 2013 VL 144 IS 5 BP 967 EP 977 DI 10.1053/j.gastro.2013.01.047 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 129BR UT WOS:000317813900026 PM 23380084 ER PT J AU Hoshida, Y Villanueva, A Sangiovanni, A Sole, M Hur, C Andersson, KL Chung, RT Gould, J Kojima, K Gupta, S Taylor, B Crenshaw, A Gabriel, S Minguez, B Iavarone, M Friedman, SL Colombo, M Llovet, JM Golub, TR AF Hoshida, Yujin Villanueva, Augusto Sangiovanni, Angelo Sole, Manel Hur, Chin Andersson, Karin L. Chung, Raymond T. Gould, Joshua Kojima, Kensuke Gupta, Supriya Taylor, Bradley Crenshaw, Andrew Gabriel, Stacey Minguez, Beatriz Iavarone, Massimo Friedman, Scott L. Colombo, Massimo Llovet, Josep M. Golub, Todd R. TI Prognostic Gene Expression Signature for Patients With Hepatitis C-Related Early-Stage Cirrhosis SO GASTROENTEROLOGY LA English DT Article DE Liver Cancer Prevention; Early Detection; Screening; Whole Genome Gene Expression Profiling ID GROWTH-FACTOR GENE; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; FUNCTIONAL POLYMORPHISM; INCREASED SURVIVAL; FIBROSIS; SURVEILLANCE; RISK; CHALLENGES; STRATEGIES AB BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC. C1 [Hoshida, Yujin; Kojima, Kensuke; Minguez, Beatriz; Friedman, Scott L.; Llovet, Josep M.] Icahn Sch Med Mt Sinai, Div Liver Dis, Mt Sinai Liver Canc Program, Dept Med,Tisch Canc Inst, New York, NY 10029 USA. [Villanueva, Augusto; Llovet, Josep M.] Hosp Clin Barcelona, HCC Translat Res Lab, Inst Invest Biomed August Pi I Sunyer, Ctr Invest Red Enfermedades Hepat & Digest, Barcelona, Spain. [Sole, Manel] Hosp Clin Barcelona, Ctr Invest Red Enfermedades Hepat & Digest, Inst Invest Biomed August Pi I Sunyer, Dept Pathol,Barcelona Clin Liver Canc Grp, Barcelona, Spain. [Sangiovanni, Angelo; Iavarone, Massimo; Colombo, Massimo] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, M&A Migliavacca Ctr Liver Dis, Milan, Italy. [Sangiovanni, Angelo; Iavarone, Massimo; Colombo, Massimo] Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Div Gastroenterol 1, Milan, Italy. [Hur, Chin; Andersson, Karin L.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gould, Joshua; Gupta, Supriya; Taylor, Bradley; Crenshaw, Andrew; Gabriel, Stacey; Golub, Todd R.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. [Golub, Todd R.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Hoshida, Y (reprint author), Leon & Norma Hess Ctr Sci & Med, Div Liver Dis, Mt Sinai Liver Canc Program, Icahn Sch Med Mt Sinai,Dept Med,Tisch Canc Inst, 1470 Madison Ave, New York, NY 10029 USA. EM yujin.hoshida@mssm.edu; josep.llovet@mssm.edu; golub@broadinstitute.org RI Augusto, Villanueva/F-9378-2012; Minguez, Beatriz/N-4456-2014; Llovet, Josep M /D-4340-2014; OI Augusto, Villanueva/0000-0003-3585-3727; Minguez, Beatriz/0000-0002-7276-9666; Llovet, Josep M /0000-0003-0547-2667; Hur, Chin/0000-0002-2819-7576 FU National Institutes of Health [DK37340, DK56601, AA017067, 1R01DK076986-01, DK078772, AI069939]; Asociacion Espanola Contra el Cancer; European Commission-FP7 Framework (HEPTROMIC) [259744]; Spanish National Health Institute [SAF-2010-16055]; Howard Hughes Medical Institute; Samuel Waxman Cancer Research Foundation; European Association for the Study of the Liver (Sheila Sherlock Fellowship) FX Supported by the National Institutes of Health (DK37340, DK56601, and AA017067 to S. L. F.; 1R01DK076986-01 to J.M.L.; and DK078772 and AI069939 to R. T. C.), the Asociacion Espanola Contra el Cancer (to J.M.L.), the European Commission-FP7 Framework (HEPTROMIC, No. 259744 to J.M.L. and Y.H.), the Spanish National Health Institute (SAF-2010-16055 to J.M.L.), the Howard Hughes Medical Institute (to T. R. G.), the Samuel Waxman Cancer Research Foundation (to J.M.L.), and the European Association for the Study of the Liver (Sheila Sherlock Fellowship to A.V.). NR 39 TC 52 Z9 54 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2013 VL 144 IS 5 BP 1024 EP 1030 DI 10.1053/j.gastro.2013.01.021 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 129BR UT WOS:000317813900031 PM 23333348 ER PT J AU Lindgren, AM Hoyos, T Talkowski, ME Hanscom, C Blumenthal, I Chiang, C Ernst, C Pereira, S Ordulu, Z Clericuzio, C Drautz, JM Rosenfeld, JA Shaffer, LG Velsher, L Pynn, T Vermeesch, J Harris, DJ Gusella, JF Liao, EC Morton, CC AF Lindgren, Amelia M. Hoyos, Tatiana Talkowski, Michael E. Hanscom, Carrie Blumenthal, Ian Chiang, Colby Ernst, Carl Pereira, Shahrin Ordulu, Zehra Clericuzio, Carol Drautz, Joanne M. Rosenfeld, Jill A. Shaffer, Lisa G. Velsher, Lea Pynn, Tania Vermeesch, Joris Harris, David J. Gusella, James F. Liao, Eric C. Morton, Cynthia C. TI Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HISTONE LYSINE METHYLATION; KABUKI SYNDROME; SOTOS-SYNDROME; GENE-EXPRESSION; MENTAL-RETARDATION; BIPOLAR DISORDER; 27 DEMETHYLASE; ACTIVE GENES; MOUSE-BRAIN AB We describe a female subject (DGAP100) with a 46,X,t(X;5)(p11.3;q35.3)inv(5)(q35.3q35.1)dn, severe psychomotor retardation with hypotonia, global postnatal growth restriction, microcephaly, globally reduced cerebral volume, seizures, facial dysmorphia and cleft palate. Fluorescence in situ hybridization and whole-genome sequencing demonstrated that the X chromosome breakpoint disrupts KDM6A in the second intron. No genes were directly disrupted on chromosome 5. KDM6A is a histone 3 lysine 27 demethylase and a histone 3 lysine 4 methyltransferase. Expression of KDM6A is significantly reduced in DGAP100 lymphoblastoid cells compared to control samples. We identified nine additional cases with neurodevelopmental delay and various other features consistent with the DGAP100 phenotype with copy number variation encompassing KDM6A from microarray databases. We evaluated haploinsufficiency of kdm6a in a zebrafish model. kdm6a is expressed in the pharyngeal arches and ethmoid plate of the developing zebrafish, while a kdm6a morpholino knockdown exhibited craniofacial defects. We conclude KDM6A dosage regulation is associated with severe and diverse structural defects and developmental abnormalities. C1 [Lindgren, Amelia M.; Pereira, Shahrin; Ordulu, Zehra; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Hoyos, Tatiana; Liao, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Dept Plast & Reconstruct Surg, Ctr Regenerat Med,Harvard Stem Cell Inst,Med Sch, Boston, MA 02115 USA. [Talkowski, Michael E.; Hanscom, Carrie; Blumenthal, Ian; Chiang, Colby; Ernst, Carl; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Talkowski, Michael E.; Gusella, James F.; Morton, Cynthia C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Clericuzio, Carol; Drautz, Joanne M.] Univ New Mexico, Dept Pediat Genet, Albuquerque, NM 87131 USA. [Rosenfeld, Jill A.; Shaffer, Lisa G.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA USA. [Velsher, Lea; Pynn, Tania] Northwestern Ontario Reg Genet Program, Thunder Bay, ON, Canada. [Vermeesch, Joris] Univ Louvain, Gasthuisberg, Netherlands. [Harris, David J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Gusella, James F.] Autism Consortium Boston, Boston, MA USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Morton, Cynthia C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, New Res Bldg,Room 160D,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cmorton@partners.org OI Chiang, Colby/0000-0002-4113-6065 FU National Institutes of Health [PO1GM061354, HD065286, MH095867]; National Institute of General Medical Sciences, and March of Dimes and Shriners Hospitals for Children FX We would like to thank DGAP100 and her family for participating in our research study and all of the healthcare professionals that contributed to this effort. We would also like to thank Mary Anne Anderson for her technical assistance at the Massachusetts General Hospital Genomics Core Facility in the Center for Human Genetic Research, Tammy Gillis and the MGH NextGen Sequencing Core, and the Cytogenetics Core of Dana Farber Harvard Cancer Center (P30 CA006516). This work was supported by PO1GM061354 (CCM), HD065286 (JFG) and MH095867 (MET) from the National Institutes of Health and the National Institute of General Medical Sciences, and March of Dimes and Shriners Hospitals for Children (ECL). NR 67 TC 16 Z9 16 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2013 VL 132 IS 5 BP 537 EP 552 DI 10.1007/s00439-013-1263-x PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 127IG UT WOS:000317691100005 PM 23354975 ER PT J AU Najavits, LM Hien, D AF Najavits, Lisa M. Hien, Denise TI Helping Vulnerable Populations: A Comprehensive Review of the Treatment Outcome Literature on Substance Use Disorder and PTSD SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; SEEKING-SAFETY THERAPY; COGNITIVE-BEHAVIORAL TREATMENT; INCARCERATED WOMEN; EMPOWERMENT-MODEL; EXPOSURE THERAPY; TRAUMA TREATMENT; ABUSE TREATMENT; DEPENDENCE AB We review treatment studies for comorbid substance use disorder (SUD) and posttraumatic stress disorder (PTSD). Results show positive outcomes on multiple domains. Most models had more effect on PTSD than SUD, suggesting SUD is harder to treat. Seeking Safety (SS) is the most studied model. It shows positive outcomes, and is the only treatment outperforming a control on both PTSD and SUD. Partial-dose SS had more mixed results than the full dose. This first-generation of PTSD/SUD research addresses complex samples excluded from gold standard PTSD-alone literature. Treatments for PTSD/SUD are generally longer than PTSD-alone treatments and present-focused, emphasizing stabilization and coping. The few models with past-focused (exposure-based) components also incorporated present-focused approaches for these vulnerable clients. We discuss public health perspectives to advance the field. C1 [Najavits, Lisa M.] Boston Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02215 USA. [Hien, Denise] CUNY City Coll, New York, NY USA. RP Najavits, LM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,116-B, Boston, MA 02130 USA. EM lisa.najavits@va.gov NR 36 TC 51 Z9 52 U1 3 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2013 VL 69 IS 5 BP 433 EP 479 DI 10.1002/jclp.21980 PG 47 WC Psychology, Clinical SC Psychology GA 130GI UT WOS:000317901100001 PM 23592045 ER PT J AU Najavits, LM AF Najavits, Lisa M. TI The Case of Jared SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article C1 [Najavits, Lisa M.] VA Boston Healthcare Syst, Boston Sch Med, Boston, MA 02130 USA. RP Najavits, LM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,116-B, Boston, MA 02130 USA. EM lisa.najavits@va.gov NR 0 TC 0 Z9 0 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2013 VL 69 IS 5 BP 480 EP 481 DI 10.1002/jclp.21981 PG 2 WC Psychology, Clinical SC Psychology GA 130GI UT WOS:000317901100002 PM 23580346 ER PT J AU Schmitz, M AF Schmitz, Martha TI The Case: Treating Jared Through Seeking Safety SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article C1 Univ Calif San Francisco, Sch Med, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Schmitz, M (reprint author), Univ Calif San Francisco, Sch Med, San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM Martha.schmitz@va.gov NR 4 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2013 VL 69 IS 5 BP 490 EP 493 DI 10.1002/jclp.21985 PG 4 WC Psychology, Clinical SC Psychology GA 130GI UT WOS:000317901100006 PM 23564554 ER PT J AU Keane, TM Najavits, LM AF Keane, Terence M. Najavits, Lisa M. TI Interview: Does Complex Trauma Exist? A "Long View" Based on Science and Service in the Trauma Field SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Keane, TM (reprint author), VA Boston Healthcare Syst, Res Serv 151, 150 South Huntington Ave, Boston, MA 02130 USA. EM terry.keane@va.gov NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2013 VL 69 IS 5 BP 510 EP 515 DI 10.1002/jclp.21991 PG 6 WC Psychology, Clinical SC Psychology GA 130GI UT WOS:000317901100009 PM 23564601 ER PT J AU van der Kolk, B Najavits, LM AF van der Kolk, Bessel Najavits, Lisa M. TI Interview: What is PTSD Really? Surprises, Twists of History, and the Politics of Diagnosis and Treatment SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article C1 [van der Kolk, Bessel] Justice Resource Inst, Ctr Trauma, Brookline, MA 02446 USA. [Najavits, Lisa M.] VA Boston Healthcare Syst, Boston, MA USA. [Najavits, Lisa M.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP van der Kolk, B (reprint author), Justice Resource Inst, Ctr Trauma, 1269 Beacon St, Brookline, MA 02446 USA. EM bvanderk@traumacenter.org NR 0 TC 2 Z9 2 U1 8 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2013 VL 69 IS 5 BP 516 EP 522 DI 10.1002/jclp.21992 PG 7 WC Psychology, Clinical SC Psychology GA 130GI UT WOS:000317901100010 PM 23592047 ER PT J AU Landes, SJ Garovoy, ND Burkman, KM AF Landes, Sara J. Garovoy, Natara D. Burkman, Kristine M. TI Treating Complex Trauma Among Veterans: Three Stage-Based Treatment Models SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE complex trauma; Veterans; treatment; dialectical behavior therapy; STAIR narrative therapy; seeking safety ID THERAPY; PTSD AB This article addresses the issue of complex trauma in veterans and treatments for symptom presentations resulting from complex trauma exposure. While various definitions have been proposed for complex trauma, the clinical issues related to it are relevant for veterans as they are at risk for cumulative trauma exposures such as multiple combat deployments and military sexual trauma. Several treatments were either developed to address and/or implemented with complex trauma. This article discusses three of these treatments that share a stage-based approach, focusing on the present (e.g., skills training and psychoeducation), which can then be followed, if needed, with a past-focused (e.g., exposure-based) treatment: Dialectical Behavior Therapy (Linehan, 1993), Seeking Safety (Najavits, 2002), Skills Training in Affective and Interpersonal Regulation (STAIR) Narrative Therapy (Cloitre, Cohen, & Koenen, 2006). This article also discusses what is currently being done to address symptom presentations resulting from complex trauma exposure and challenges and possible solutions to implementing this care. C1 [Landes, Sara J.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA. [Garovoy, Natara D.] VA Palo Alto Hlth Care Syst, Womens Prevent Outreach & Educ Ctr, Menlo Pk, CA 94025 USA. [Burkman, Kristine M.] San Francisco VA Med Ctr, PTSD Res Program, San Francisco, CA USA. RP Landes, SJ (reprint author), VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM sara.landes@va.gov OI Landes, Sara/0000-0001-8515-2465 NR 10 TC 2 Z9 2 U1 1 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2013 VL 69 IS 5 BP 523 EP 533 DI 10.1002/jclp.21988 PG 11 WC Psychology, Clinical SC Psychology GA 130GI UT WOS:000317901100011 PM 23529776 ER PT J AU King, LY Chung, RT AF King, Lindsay Y. Chung, Raymond T. TI IL28B testing in a rapidly changing world: Still relevant? SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID GENOTYPE 1 INFECTION; CHRONIC HEPATITIS-C; COST-EFFECTIVENESS; VIRUS-INFECTION; HCV INFECTION; TELAPREVIR; BOCEPREVIR; RIBAVIRIN; PEGINTERFERON; THERAPY C1 [King, Lindsay Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM rtchung@partners.org NR 18 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD MAY PY 2013 VL 58 IS 5 BP 847 EP 849 DI 10.1016/j.jhep.2013.02.002 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 130CL UT WOS:000317890200002 PM 23416431 ER PT J AU Chren, MM Linos, E Torres, JS Stuart, SE Parvataneni, R Boscardin, WJ AF Chren, Mary-Margaret Linos, Eleni Torres, Jeanette S. Stuart, Sarah E. Parvataneni, Rupa Boscardin, W. John TI Tumor Recurrence 5 Years after Treatment of Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MOHS MICROGRAPHIC SURGERY; NONMELANOMA SKIN-CANCER; SURGICAL EXCISION; COST-EFFECTIVENESS; PRIVATE-PRACTICE; FACE; VALIDITY AB For most cutaneous basal cell and squamous cell carcinomas (nonnnelanoma skin cancers (NMSCs)), data are insufficient to permit evidence-based choices among treatments. To compare tumor recurrence after treatments, we conducted a prospective cohort study of consecutive patients with primary NMSCs treated with the most common treatments, in two practices in 1999-2000. Recurrence was determined from medical records by observers blinded to treatment type. Follow-up was available for 1,174 patients with 1,488 tumors (93.8%) at median 7.4 years; of these tumors, 24.3% (N=361) were treated with destruction with electrodessication/curettage, 38.3% (N=571) with excision, and 37.4% (N=556) with histologically guided serial excision (Mohs surgery). The overall 5-year tumor recurrence rate (95% confidence interval) was 3.3% (2.3, 4.4). Unadjusted recurrence rates did not differ after treatments: 4.9% (2.3, 7.4) after destruction, 3.5% (1.8, 5.2) after excision, and 2.1% (0.6, 3.5) after Mohs surgery (P=0.26), and no difference was seen after adjustment for risk factors. In tumors treated only with excision or Mohs surgery, the hazard of recurrence was not significantly different, even after adjustment for propensity for treatment with Mohs surgery. These data indicate that common treatments for NMSCs were at least 95% effective, and further studies are needed to guide therapeutic choices for different clinical subgroups. C1 [Chren, Mary-Margaret; Linos, Eleni; Stuart, Sarah E.; Parvataneni, Rupa] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Chren, Mary-Margaret; Torres, Jeanette S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Chren, MM (reprint author), Zion Canc Res Bldg,2340 Sutter St,Room N412,Box 0, San Francisco, CA 94143 USA. EM chrenm@derm.ucsf.edu RI Linos, Eleni/C-4392-2014; OI Linos, Eleni/0000-0002-5856-6301; , Eleni/0000-0003-2538-0700 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [R01 AR 054983, K02 AR02203, K24 AR052667]; Investigator-Initiated Research Grants [IIRs 97010-2 and 04-043-3]; Health Services Research Enhancement Award Program (REAP) of the Health Services Research; Development Service of the Department of Veterans Affairs FX This work was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (R01 AR 054983, K02 AR02203, and K24 AR052667), and by Investigator-Initiated Research Grants (IIRs 97010-2 and 04-043-3) and the Health Services Research Enhancement Award Program (REAP) of the Health Services Research and Development Service of the Department of Veterans Affairs. NR 29 TC 50 Z9 51 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 IS 5 BP 1188 EP 1196 DI 10.1038/jid.2012.403 PG 9 WC Dermatology SC Dermatology GA 127KV UT WOS:000317698800014 PM 23190903 ER PT J AU Ang, C Anyanwu, C Werth, V AF Ang, C. Anyanwu, C. Werth, V. TI Mechanic's hands are predictive of reduced lung diffusion capacity and interstitial lung disease in patients with dermatomyositis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Ang, C.; Anyanwu, C.; Werth, V.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Ang, C.; Anyanwu, C.; Werth, V.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Ang, C.] Changi Gen Hosp, Dept Dermatol, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1121 BP S190 EP S190 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901410 ER PT J AU Anyanwu, CO Propert, KJ Werth, VP AF Anyanwu, C. O. Propert, K. J. Werth, V. P. TI Determination of cutaneous dermatomyositis severity using the cutaneous dermatomyositis disease area and severity index SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Anyanwu, C. O.; Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Dept Dermatol, Philadelphia, PA USA. [Anyanwu, C. O.; Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Propert, K. J.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 216 BP S36 EP S36 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900216 ER PT J AU Chang, YC Propert, KJ Werth, VP AF Chang, Y. C. Propert, K. J. Werth, V. P. TI The limitations in measuring improvement in disease activity in patients with mild cutaneous lupus erythematosus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Chang, Y. C.; Werth, V. P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chang, Y. C.; Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Propert, K. J.] Hosp Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 190 BP S32 EP S32 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900190 ER PT J AU Chang, YC Propert, KJ Sirignano, S Chong, B Werth, VP AF Chang, Y. C. Propert, K. J. Sirignano, S. Chong, B. Werth, V. P. TI Disease flare and progression in cutaneous lupus erythematosus: A longitudinal study of CLE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Chang, Y. C.; Werth, V. P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chang, Y. C.; Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Propert, K. J.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Sirignano, S.; Chong, B.] UT Southwestern, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 189 BP S32 EP S32 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900189 ER PT J AU Devlin, P Chaney, K Carter, J Tawa, M Fisher, DC Dorosario, A Adams, N Watanabe, R Clark, R Kupper, TS AF Devlin, P. Chaney, K. Carter, J. Tawa, M. Fisher, D. C. Dorosario, A. Adams, N. Watanabe, R. Clark, R. Kupper, T. S. TI Low-dose local ionizing radiation provides "targeted" therapy and induces durable remission in early stage mycosis fungoides/CTCL SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Devlin, P.; Chaney, K.; Carter, J.; Tawa, M.; Fisher, D. C.; Dorosario, A.; Adams, N.; Watanabe, R.; Clark, R.; Kupper, T. S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1103 BP S187 EP S187 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901392 ER PT J AU Elmariah, SB Conniff, T Luo, T Azimi, E Reddy, VB Lerner, EA Wolpowitz, D AF Elmariah, S. B. Conniff, T. Luo, T. Azimi, E. Reddy, V. B. Lerner, E. A. Wolpowitz, D. TI Altered cutaneous neural innervation in pruritic dermatoses SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Elmariah, S. B.; Luo, T.; Azimi, E.; Reddy, V. B.; Lerner, E. A.] Massachusetts Gen Hosp, Charlestown, MA USA. [Conniff, T.; Wolpowitz, D.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 701 BP S119 EP S119 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900697 ER PT J AU Enamandram, M Donahue, KR Duncan, LM Kimball, AB AF Enamandram, M. Donahue, K. R. Duncan, L. M. Kimball, A. B. TI Incidence of nonmelanoma skin cancer in patients presenting for routine dermatological care SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 548 BP S94 EP S94 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900545 ER PT J AU Freeman, EE Evans, R Maurer, T Muhe, L Easterbrook, P AF Freeman, E. E. Evans, R. Maurer, T. Muhe, L. Easterbrook, P. TI The need for unified international guidance on HIV dermatology SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Freeman, E. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evans, R.; Easterbrook, P.] World Hlth Org, HIV Dept, Geneva, Switzerland. [Muhe, L.] World Hlth Org, Geneva, Switzerland. [Maurer, T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 562 BP S96 EP S96 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900559 ER PT J AU Freeman, EE Easterbrook, P Muhe, L Hay, R Martin, J Maurer, T AF Freeman, E. E. Easterbrook, P. Muhe, L. Hay, R. Martin, J. Maurer, T. TI The role of evidence based dermatology in World Health Organization guidelines SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Freeman, E. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Easterbrook, P.] World Hlth Org, HIV Dept, Geneva, Switzerland. [Muhe, L.] World Hlth Org, Dept Child & Adolescent Hlth & Dev, Geneva, Switzerland. [Hay, R.] Int Fdn Dermatol, London, England. [Martin, J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Maurer, T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 561 BP S96 EP S96 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900558 ER PT J AU Garibyan, L Wang, LC Cotter, SE Dorosario, A Devlin, PM AF Garibyan, L. Wang, L. C. Cotter, S. E. Dorosario, A. Devlin, P. M. TI Palliative treatment for in-transit cutaneous metastases of Merkel cell carcinoma using surface-mold computer-optimized high-dose-rate brachytherapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Garibyan, L.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Dorosario, A.; Devlin, P. M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Garibyan, L.; Wang, L. C.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Cotter, S. E.] Canc Ctr Santa Barbara, Santa Barbara, CA USA. [Wang, L. C.] Mercy Med Ctr, Inst Canc Care, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 944 BP S161 EP S161 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901238 ER PT J AU Guenova, E Watanabe, R Gehad, A Teague, JE Adams, N Dorosario, AA Glinert, R Walsch, D Tawa, M Carter, JB Chaney, KA Fisher, DC Cutler, CS Kupper, TS Clark, RA AF Guenova, E. Watanabe, R. Gehad, A. Teague, J. E. Adams, N. Dorosario, A. A. Glinert, R. Walsch, D. Tawa, M. Carter, J. B. Chaney, K. A. Fisher, D. C. Cutler, C. S. Kupper, T. S. Clark, R. A. TI Reversible suppression of normal thymic output in patients with leukemic cutaneous T cell lymphoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Guenova, E.; Watanabe, R.; Gehad, A.; Teague, J. E.; Kupper, T. S.; Clark, R. A.] Harvard Skin Dis Res Ctr, Boston, MA USA. [Adams, N.; Dorosario, A. A.; Glinert, R.; Walsch, D.; Tawa, M.; Carter, J. B.; Chaney, K. A.; Fisher, D. C.; Cutler, C. S.; Kupper, T. S.; Clark, R. A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RI Guenova, Emmanuella/A-4656-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1064 BP S181 EP S181 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901357 ER PT J AU Huang, V Dowlatshahi, M Keskin, DB Reinhold, B Mayo, TC Teague, J Gehad, A Reinherz, EL Shuda, M DeCaprio, IA Thakuria, M Dorosario, AA Clark, R AF Huang, V. Dowlatshahi, M. Keskin, D. B. Reinhold, B. Mayo, T. C. Teague, J. Gehad, A. Reinherz, E. L. Shuda, M. DeCaprio, I. A. Thakuria, M. Dorosario, A. A. Clark, R. TI Defective expression of class I antigen presentation pathway members in Merkel cell carcinoma may underlie low MHC I expression and contribute to immune evasion SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Huang, V.; Dowlatshahi, M.; Keskin, D. B.; Reinhold, B.; Teague, J.; Gehad, A.; Reinherz, E. L.; DeCaprio, I. A.; Thakuria, M.; Dorosario, A. A.; Clark, R.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Mayo, T. C.; Shuda, M.] Univ Pittsburgh, Canc Virol Program, Pittsburgh, PA USA. RI SHUDA, MASAHIRO/F-5505-2011 OI SHUDA, MASAHIRO/0000-0003-0595-2572 NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 259 BP S44 EP S44 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900259 ER PT J AU Jain, R Abtin, A Roediger, B Brzoska, AJ Mitchell, AJ Ng, LG Cavanagh, LL von Andrian, UH Firth, N Weninger, W AF Jain, R. Abtin, A. Roediger, B. Brzoska, A. J. Mitchell, A. J. Ng, L. G. Cavanagh, L. L. von Andrian, U. H. Firth, N. Weninger, W. TI Perivascular macrophages are key regulators of neutrophil recruitment during skin infection and are targeted by a Staphylococcus aureus virulence factor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Jain, R.; Abtin, A.; Roediger, B.; Mitchell, A. J.; Cavanagh, L. L.; Weninger, W.] Centenary Inst, Newtown, NSW, Australia. [Brzoska, A. J.; Firth, N.] Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia. [Ng, L. G.] Biopolis, Singapore Immunol Network, Singapore, Singapore. [Cavanagh, L. L.] Sydney Med Sch, Sydney, NSW, Australia. [von Andrian, U. H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Weninger, W.] Sydney Med Sch, Discipline Dermatol, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1169 BP S198 EP S198 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901458 ER PT J AU Jalian, H Tam, J Garibyan, L Anderson, R AF Jalian, H. Tam, J. Garibyan, L. Anderson, R. TI Selective cryolysis of sebaceous glands SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Jalian, H.; Tam, J.; Garibyan, L.; Anderson, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jalian, H.] Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1078 BP S183 EP S183 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901370 ER PT J AU Katiyar, SK Prasad, R AF Katiyar, S. K. Prasad, R. TI Prostaglandin E2 promotes UV radiation-induced immune suppression via DNA hypermethylation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Katiyar, S. K.; Prasad, R.] Univ Alabama Birmingham, Birmingham, AL USA. [Katiyar, S. K.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1243 BP S211 EP S211 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901532 ER PT J AU Kimball, AB Krueger, J Sullivan, T Arbeit, RD AF Kimball, A. B. Krueger, J. Sullivan, T. Arbeit, R. D. TI IMO-3100, an antagonist of Toll-like receptor (TLR) 7 and TLR9, demonstrates clinical activity in psoriasis patients with 4 weeks of treatment in a phase 2a trial SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Krueger, J.] Rockefeller Univ, New York, NY 10021 USA. [Sullivan, T.; Arbeit, R. D.] Idera Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 156 BP S26 EP S26 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900156 ER PT J AU Korgavkar, K Xiong, M Marcolivio, K Lew, R Firoz, E Weinstock, M AF Korgavkar, K. Xiong, M. Marcolivio, K. Lew, R. Firoz, E. Weinstock, M. CA VAKCC Trial Grp TI Measuring the severity of topical 5-fluorouracil toxicity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Korgavkar, K.; Xiong, M.; Marcolivio, K.; Weinstock, M.] VA Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. [Marcolivio, K.; Lew, R.; Weinstock, M.; VAKCC Trial Grp] VA Cooperat Studies Program, Boston, MA USA. [Korgavkar, K.; Xiong, M.; Firoz, E.; Weinstock, M.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 521 BP S89 EP S89 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900518 ER PT J AU Lee, N Kleffel, S Lezcano, MC Sobolewski, K DoRosario, A Frank, MH Wang, L Murphy, GF Schatton, T AF Lee, N. Kleffel, S. Lezcano, M. C. Sobolewski, K. DoRosario, A. Frank, M. H. Wang, L. Murphy, G. F. Schatton, T. TI ABCB5 identifies a chemorefractory cell population in Merkel cell carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Lee, N.; Kleffel, S.; Sobolewski, K.; Frank, M. H.; Wang, L.; Schatton, T.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Lezcano, M. C.; Murphy, G. F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [DoRosario, A.; Wang, L.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Frank, M. H.; Schatton, T.] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 358 BP S61 EP S61 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900356 ER PT J AU Lefort, K Brooks, Y Ostano, P Carlo-Andre, M Calpini, V Albinger-Hegyi, A Hoetzenecker, W Dotto, G AF Lefort, K. Brooks, Y. Ostano, P. Carlo-Andre, M. Calpini, V. Albinger-Hegyi, A. Hoetzenecker, W. Dotto, G. TI A miR-34a-SIRT6 axis in the squamous cell differentiation network SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Lefort, K.; Calpini, V.; Hoetzenecker, W.; Dotto, G.] Univ Lausanne, CH-1066 Epalinges, Switzerland. [Lefort, K.] CHU Vaudois, Lausanne, Switzerland. [Brooks, Y.; Dotto, G.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Ostano, P.] Fdn Edo & Elvo Tempia Valenta, Lab Canc Genom, Biella, Italy. [Carlo-Andre, M.] INSERM, U876, Bordeaux, France. [Carlo-Andre, M.] Bordeaux Hosp, Natl Reference Ctr Rare Skin Dis, Bordeaux, France. [Albinger-Hegyi, A.] HNO Zuerich Fraumunster, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 442 BP S75 EP S75 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900439 ER PT J AU Reddy, VB Elmariah, SB Azimi, E Luo, T Lerner, EA AF Reddy, V. B. Elmariah, S. B. Azimi, E. Luo, T. Lerner, E. A. TI Mechanisms of itch: Proteases activate Man-related G-protein coupled receptors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Reddy, V. B.; Elmariah, S. B.; Azimi, E.; Luo, T.; Lerner, E. A.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 244 BP S41 EP S41 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900244 ER PT J AU Rubina, S Camp, WL Hermann, J Cantrell, W Cantor, AB Athar, M Elmets, CA AF Rubina, S. Camp, W. L. Hermann, J. Cantrell, W. Cantor, A. B. Athar, M. Elmets, C. A. TI Tanning beds use and skin cancer biomarkers - a pilot study SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Rubina, S.; Camp, W. L.; Hermann, J.; Cantrell, W.; Athar, M.; Elmets, C. A.] UAB, Birmingham, AL USA. [Athar, M.; Elmets, C. A.] UAB, SDRC, Birmingham, AL USA. [Cantor, A. B.] UAB, Div Prevent Med, Birmingham, AL USA. [Elmets, C. A.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1289 BP S219 EP S219 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901578 ER PT J AU Sadik, CD Kim, ND Luster, AD AF Sadik, C. D. Kim, N. D. Luster, A. D. TI Neutrophils orchestrate their own recruitment in immune complex-induced inflammation by C5aR and Fc gamma R signaling SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Sadik, C. D.; Kim, N. D.; Luster, A. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Sadik, C. D.] UKSH, Dermatol Allergy & Venereol 2Dept, Lubeck, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 197 BP S33 EP S33 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900197 ER PT J AU Strazzula, L Nigwekar, S Steele, D Tsiaras, W Sise, M Bis, S Smith, GP Kroshinsky, D AF Strazzula, L. Nigwekar, S. Steele, D. Tsiaras, W. Sise, M. Bis, S. Smith, G. P. Kroshinsky, D. TI Intralesional sodium thiosulfate for the treatment of cutaneous calciphylaxis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Strazzula, L.; Nigwekar, S.; Steele, D.; Tsiaras, W.; Sise, M.; Bis, S.; Smith, G. P.; Kroshinsky, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI sebastianovitsch, stepan/G-8507-2013 NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1120 BP S190 EP S190 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901412 ER PT J AU Strazzula, L Pratt, D Zardas, J Kroshinsky, D AF Strazzula, L. Pratt, D. Zardas, J. Kroshinsky, D. TI Dermatology consultation may decrease telaprevir discontinuation among patients with severe triple therapy-associated rash SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Strazzula, L.; Pratt, D.; Zardas, J.; Kroshinsky, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1115 BP S189 EP S189 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901404 ER PT J AU Strazzula, L Garibyan, L Oaklander, AL Kroshinsky, D AF Strazzula, L. Garibyan, L. Oaklander, A. L. Kroshinsky, D. TI Delusions of parasitosis: A possible neuropathic component SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Strazzula, L.; Garibyan, L.; Oaklander, A. L.; Kroshinsky, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1108 BP S188 EP S188 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901400 ER PT J AU Strazzula, L Cotliar, J Fox, LP Gee, S Hughey, SL Shinkai, K Kroshinsky, D AF Strazzula, L. Cotliar, J. Fox, L. P. Gee, S. Hughey, S. L. Shinkai, K. Kroshinsky, D. TI Inpatient pseudocellulitis: Assessing the extent of the problem through dermatology consultation services SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Strazzula, L.; Kroshinsky, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cotliar, J.] Northwestern Med Ctr, Chicago, IL USA. [Gee, S.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Fox, L. P.; Shinkai, K.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Hughey, S. L.] Univ Alabama, Tuscaloosa, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 601 BP S102 EP S102 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900598 ER PT J AU Strazzula, L Kroshinsky, D AF Strazzula, L. Kroshinsky, D. TI Recurrent cellulitis in outpatient primary care: assessing the nature of the problem SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Strazzula, L.; Kroshinsky, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 603 BP S103 EP S103 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900600 ER PT J AU Sung, SM Kimball, AB AF Sung, S. M. Kimball, A. B. TI Rising educational debt levels in dermatology trainees and effects on subsequent training choices: An update SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Sung, S. M.; Kimball, A. B.] Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin CURTIS, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1011 BP S172 EP S172 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901301 ER PT J AU Timares, L Nasti, T Cochran, B Jaleel, T Yusuf, N Elmets, CA AF Timares, L. Nasti, T. Cochran, B. Jaleel, T. Yusuf, N. Elmets, C. A. TI A new mouse model for studying the development of melanomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Timares, L.; Nasti, T.; Cochran, B.; Jaleel, T.; Yusuf, N.; Elmets, C. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Timares, L.; Yusuf, N.; Elmets, C. A.] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL USA. [Elmets, C. A.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1400 BP S238 EP S238 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901688 ER PT J AU Vaid, M Katiyar, SK AF Vaid, M. Katiyar, S. K. TI Proanthocyanidins inhibit invasive potential of human melanoma cells by targeting beta-catenin signaling SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Vaid, M.; Katiyar, S. K.] Univ Alabama Birmingham, Birmingham, AL USA. [Katiyar, S. K.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 1323 BP S225 EP S225 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698901613 ER PT J AU Velez, NF Karia, PS Guo, Y Vartanov, AR Davids, MS Brown, JR Neel, VA Schmults, CD AF Velez, N. F. Karia, P. S. Guo, Y. Vartanov, A. R. Davids, M. S. Brown, J. R. Neel, V. A. Schmults, C. D. TI Advanced Rai stage and skin cancer tumor stage predicts outcomes of skin cancer in patients with chronic lymphocytic leukemia SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Karia, P. S.; Guo, Y.; Schmults, C. D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Vartanov, A. R.; Davids, M. S.; Brown, J. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Velez, N. F.; Neel, V. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 534 BP S91 EP S91 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900531 ER PT J AU Watanabe, R Guenova, E Gehad, A Teague, J Adams, N Dorosario, AA Glinert, R Tawa, M Carter, JB Chaney, KA Fisher, DC Kupper, TS Clark, RA AF Watanabe, R. Guenova, E. Gehad, A. Teague, J. Adams, N. Dorosario, A. A. Glinert, R. Tawa, M. Carter, J. B. Chaney, K. A. Fisher, D. C. Kupper, T. S. Clark, R. A. TI Reversible Th22 dysfunction and persistent loss of Th17 responses in patients with L-CTCL SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Watanabe, R.; Guenova, E.; Gehad, A.; Teague, J.; Adams, N.; Dorosario, A. A.; Glinert, R.; Tawa, M.; Carter, J. B.; Chaney, K. A.; Fisher, D. C.; Kupper, T. S.; Clark, R. A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RI Guenova, Emmanuella/A-4656-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 258 BP S43 EP S43 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900258 ER PT J AU Wehner, MR Linos, E Parvataneni, R Stuart, SE Boscardin, WJ Chren, M AF Wehner, M. R. Linos, E. Parvataneni, R. Stuart, S. E. Boscardin, W. J. Chren, M. TI Risk of subsequent non-melanoma skin cancers in patients with prior non-melanoma skin cancer SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [Wehner, M. R.; Linos, E.; Parvataneni, R.; Stuart, S. E.; Boscardin, W. J.; Chren, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wehner, M. R.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Chren, M.] San Francisco VA Med Ctr, San Francisco, CA USA. RI Linos, Eleni/C-4392-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 547 BP S93 EP S93 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900544 ER PT J AU Erakat, MS Chuang, SK Shanti, RM Ziccardi, VB AF Erakat, Mohammed S. Chuang, Sung-Kiang Shanti, Rabie M. Ziccardi, Vincent B. TI Interval Between Injury and Lingual Nerve Repair as a Prognostic Factor for Success Using Type I Collagen Conduit SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID FUNCTIONAL SENSORY RECOVERY AB Purpose: The purpose of the present study was to investigate the role of a type I collagen nerve conduit in the repair of lingual nerve injuries compared with those lingual nerve repairs performed without a collagen membrane and to identify the prognostic factors for functional sensory recovery (FSR). Materials and Methods: This was a retrospective cohort study evaluating a sample derived from the population of patients who had undergone lingual nerve microsurgery from March 17, 2000, to February 23, 2010 by the same surgeon (V.B.Z.) with complete records available, including follow-up assessments. The primary outcome variable was the interval to successful FSR according to the British Medical Research Council criteria for FSR. The predictor variables were categorized into demographic, surgical, and clinical sensory testing. Appropriate descriptive statistics and univariate and multivariate Cox proportional hazards survival statistics were computed in analyzing the patient age at lingual nerve injury repair (in years), gender, timing of surgical intervention, mechanism of injury, specific surgical procedures, and application of a type I collagen conduit. Results: The study cohort included 41 patients with 42 lingual nerve injuries who underwent surgical repair. Their mean age was 28.3 +/- 8.3 years (range 13 to 44), with 88% females (n = 32). In the multivariate model, the injury to surgery interval per 1-month increase (hazard ratio 1.23, 95% confidence interval 1.02 to 1.48, P = .029) and injury to surgery interval of 9 months or longer (hazard ratio 4.67, 95% confidence interval 1.04 to 20.87, P = .04) remained significantly associated statistically with successful FSR. Conclusions: The results of the present study have demonstrated that the injury to surgery interval is the most significant prognostic factor in the repair of lingual nerve injuries. The use of the collagen membrane demonstrated a greater level of FSR compared with those treated without the use of the membrane. However, the results from the collagen conduit were not statistically significant. (C) 2013 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 71:833-838, 2013 C1 [Erakat, Mohammed S.] Warren Oral Surg, Warren, NJ USA. [Erakat, Mohammed S.; Shanti, Rabie M.; Ziccardi, Vincent B.] Univ Med & Dent New Jersey, Dept Oral & Maxillofacial Surg, Newark, NJ 07103 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Ziccardi, VB (reprint author), Univ Med & Dent New Jersey, Dept Oral & Maxillofacial Surg, 110 Bergen St,Room B-854, Newark, NJ 07103 USA. EM ziccarvb@umdnj.edu NR 11 TC 1 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2013 VL 71 IS 5 BP 833 EP 838 DI 10.1016/j.joms.2011.11.026 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 128AL UT WOS:000317740300009 PM 22365982 ER PT J AU Laviv, A Seldin, EB Dodson, TB AF Laviv, Amir Seldin, Edward B. Dodson, Thomas B. TI A Simple Modification to the Nasal Hood to Facilitate Capnographic Measurements: A Technical Note SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article C1 [Laviv, Amir; Seldin, Edward B.; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Laviv, A (reprint author), 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM amirlaviv@gmail.com NR 1 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2013 VL 71 IS 5 BP 854 EP 855 DI 10.1016/j.joms.2013.01.023 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 128AL UT WOS:000317740300012 PM 23598550 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Antibiotic exposure is associated with development of inflammatory bowel disease SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 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 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2013 VL 162 IS 5 BP 1077 EP 1077 PG 1 WC Pediatrics SC Pediatrics GA 129JW UT WOS:000317836300046 PM 23617975 ER PT J AU Watson, AJ Redbord, K Taylor, JS Shippy, A Kostecki, J Swerlick, R AF Watson, Alice J. Redbord, Kelley Taylor, James S. Shippy, Alison Kostecki, James Swerlick, Robert TI Medical error in dermatology practice: Development of a classification system to drive priority setting in patient safety efforts SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE medical error; patient safety; practice improvement; quality of care; Universal Protocol; wrong-site surgery ID BIOPSY-SITE PHOTOGRAPHY; PHYSICIAN SURVEY; FOLLOW-UP; CARE; PSORIASIS; SURGERY; QUALITY; RISK AB Background: To date, no study to our knowledge has examined the nature and scope of medical error in dermatology practice. Objective: We sought to collect and categorize physician-reported errors in dermatology practice. Methods: A survey regarding most recent and most serious errors was developed and distributed to dermatologists attending US meetings. A total of 150 responses were received outlining 152 most recent errors and 130 most serious errors. Survey responses, along with classification systems for other specialties, were used to develop a classification system for medical error in dermatology. Results: The respondents' demographics reflected the specialty: 63% were male, 60% were older than 50 years, and 60% were in solo or group private practice. Of the most recent errors reported, 85% happened once a year or less, and 86% did not result in harm to patients. The most common categories of both most recent and most serious errors were related to assessment (41% and 31%, respectively) and interventions (44% and 52%, respectively). Assessment errors were primarily related to investigations, and commonly involved the biopsy pathway. Intervention errors in the most recent and most serious errors were split between those related to medication (54% and 27%) and those related to procedures (46% and 73%). Of note, 5 and 21 wrong-site surgeries were reported in the most recent and most serious errors groups, respectively. Limitations: Our findings are subject to respondent and recall bias and our classification system, although an important first step, is likely incomplete. Conclusion: Our findings highlight several key areas of patient care in need of safety initiatives, namely the biopsy pathway, medication management, and prevention of wrong-site surgery. (J Am Acad Dermatol 2013;68:729-37.) C1 [Watson, Alice J.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Watson, Alice J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Redbord, Kelley] George Washington Univ, Washington, DC USA. [Taylor, James S.] Cleveland Clin, Dept Dermatol, Cleveland, OH 44195 USA. [Shippy, Alison; Kostecki, James] Amer Acad Dermatol, Washington, DC USA. [Swerlick, Robert] Emory Med Sch, Atlanta, GA USA. RP Watson, AJ (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM AJWatson@partners.org NR 27 TC 11 Z9 11 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2013 VL 68 IS 5 BP 729 EP 737 DI 10.1016/j.jaad.2012.10.058 PG 9 WC Dermatology SC Dermatology GA 129IV UT WOS:000317833500011 PM 23360864 ER PT J AU Kimball, AB Pariser, D Yamauchi, PS Menter, A Teller, CF Shi, YF Yong, M Creamer, K Hooper, M Aras, G Kricorian, G Gelfand, JM AF Kimball, Alexa B. Pariser, David Yamauchi, Paul S. Menter, Alan Teller, Craig F. Shi, Yifei Yong, Mellissa Creamer, Kara Hooper, Michele Aras, Girish Kricorian, Gregory Gelfand, Joel M. TI OBSERVE-5 interim analysis: An observational postmarketing safety registry of etanercept for the treatment of psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE etanercept; infections; lymphoma; nonmelanoma skin cancer; psoriasis; registry; safety ID LONG-TERM SAFETY; TRIAL; EFFICACY; MONOTHERAPY; ARTHRITIS AB Background: Etanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults. Objective: We sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective. Methods: OBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period. Results: A total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database. Limitations: The registry lacks a control group, and the study is too small to measure the frequency of rare events. Conclusion: Etanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed. (J Am Acad Dermatol 2013;68:756-64.) C1 [Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yamauchi, Paul S.] Inst Dermatol, Santa Monica, CA USA. [Yamauchi, Paul S.] Skin Care Ctr, Santa Monica, CA USA. [Menter, Alan] Baylor Res Inst, Dallas, TX USA. [Shi, Yifei; Yong, Mellissa; Creamer, Kara; Hooper, Michele; Aras, Girish; Kricorian, Gregory] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, 50 Staniford St,240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Immunex Corp; Amgen Inc; Janssen Pharmaceuticals Inc. FX Funded by Immunex Corp, a wholly owned subsidiary of Amgen Inc. Dikran Toroser of Amgen Inc and Karen Zimmermann and Rick Davis of Complete Healthcare Communications (funded by Amgen Inc) provided medical writing support.; Dr Kimball is an investigator and consultant for Amgen Inc, Abbott Laboratories, Idera, Janssen Pharmaceuticals Inc, Merck, Pfizer Inc, and VBL Therapeutics. She consults with Novartis and has fellowship funding from Janssen Pharmaceuticals Inc. Dr Pariser is an investigator and consultant for Abbott Laboratories, Amgen Inc, Astellas, Celgene, Novartis, and Valeant Pharmaceuticals International. He is an investigator and serves on an advisory board for Galderma Laboratories LP, Ortho Dermatologics, Pfizer Inc, and Stiefel. He is an investigator for Basilea, Dow Pharmaceutical Sciences Inc, Eli Lilly and Co, Graceway Pharmaceuticals LLC, Intendis Inc, Novo Nordisk, Peplin Inc, and Photocure ASA. He serves on an advisory board for Genentech Inc, Janssen-Ortho Inc, and Medicis Pharmaceuticals Corp. He is a consultant for Mela Sciences and has received honoraria from LEO Pharma US. Dr Yamauchi serves on advisory boards and is a speaker, consultant, and investigator for Abbott Laboratories, Amgen Inc, and Centocor. Dr Menter serves on advisory boards and is a speaker, consultant, and investigator for Abbott Laboratories, Amgen Inc, Centocor, and Wyeth. He serves on the advisory board and is a consultant and speaker for Galderma Laboratories LP. He is a consultant and investigator for Eli Lilly and Co and Stiefel, and an investigator for Allergan, Celgene, Novartis, Novo Nordisk, Pfizer Inc, and Syntrix Biosystems. Dr Teller is a speaker for Amgen Inc, Abbott Laboratories, and Janssen Pharmaceuticals Inc. Mr Shi, Ms Creamer, and Drs Hooper, Aras, and Kricorian are currently employed by and have stock ownership in Amgen Inc. Dr Yong was employed by Amgen Inc at the time the study was conducted and currently has stock ownership in Amgen Inc. Dr Gelfand served as consultant with Abbott Laboratories, Amgen Inc, Celgene, Centocor, Novartis, and Pfizer Inc, receiving honoraria. He had grants or has pending grants from Abbott Laboratories, Amgen Inc, Genentech Inc, Novartis, and Pfizer Inc. He has received payment for CME work related to psoriasis. He also received a donation from Amgen Inc to the University of Pennsylvania to further develop the Dermatology Clinical Effectiveness Research Network. NR 18 TC 16 Z9 18 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2013 VL 68 IS 5 BP 756 EP 764 DI 10.1016/j.jaad.2012.10.055 PG 9 WC Dermatology SC Dermatology GA 129IV UT WOS:000317833500014 PM 23357569 ER PT J AU Wright, CD AF Wright, Cameron D. TI Untitled SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 [Wright, Cameron D.] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2013 VL 145 IS 5 BP 1325 EP 1325 DI 10.1016/j.jtcvs.2013.01.001 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 129LJ UT WOS:000317840600028 PM 23380511 ER PT J AU Ikonomidis, JS Ivey, CR Wheeler, JB Akerman, AW Rice, A Patel, RK Stroud, RE Shah, AA Hughes, CG Ferrari, G Mukherjee, R Jones, JA AF Ikonomidis, John S. Ivey, Charlotte R. Wheeler, Jason B. Akerman, Adam W. Rice, Allison Patel, Risha K. Stroud, Robert E. Shah, Asad A. Hughes, Chad G. Ferrari, Giovanni Mukherjee, Rupak Jones, Jeffrey A. TI Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MATRIX METALLOPROTEINASES; ENDOGENOUS INHIBITORS; DILATATION; VALVES; MATRIX-METALLOPROTEINASE-9; NORMALIZATION; EXPRESSION; MICRORNAS; SIZE AB Background: Thoracic aortic aneurysms (TAAs) develop through an asymptomatic process resulting in gross dilation that progresses to rupture if left undetected and untreated. If detected, patients with TAA are followed over time until the risk of rupture outweighs the risk of surgical repair. Current methodologies for tracking TAA size are limited to expensive computed tomography or magnetic resonance imaging because no acceptable population screening tools are currently available. Previous studies from this laboratory and others have identified differential protein profiles for the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs), in ascending TAA tissue from patients with bicuspid aortic valves (BAVs), versus patients with idiopathic degenerative disease and a tricuspid aortic valve (TAV). In addition, altered microRNA (miR) expression levels have also been reported in TAAs compared with normal aortic tissue. The objective of our study was to identify circulating factors within plasma that could serve as potential biomarkers for distinguishing etiologic subtypes of aneurysm disease. Methods: Ascending TAA tissue and plasma specimens were obtained from patients with BAV (n = 21) and TAV (n = 21) at the time of surgical resection. The protein abundance of key MMPs (1, 2, 3, 8, and 9), TIMPs (1, 2, 3, and 4), and miRs (1, 21, 29a, 133a, 143, and 145) was examined using a multianalyte protein profiling system or by quantitative polymerase chain reaction, respectively. Results were compared with normal aortic tissue and plasma obtained from patients without aortic disease (n = 10). Results: Significant (P <. 05) differences in standardized miR-1 and miR-21 abundance between BAV and TAV aortic tissue samples and different tissue and plasma profiles of analyte differences from normal aorta where observed between the BAV and TAV groups. Linear regression analysis revealed significant linear relationships in plasma and tissue measurements only for MMP-8 and TIMP-1, TIMP-3, and TIMP-4 (P <. 05). Receiver operator curve analysis revealed specific cassettes of analytes predictive of TAA disease. Relative to normal aorta, BAV proteolytic balance was significantly increased for MMP-1, MMP-2, and MMP-7, and for decreased MMP-8 and MMP-9. In contrast, TAV proteolytic balance relative to normal aorta was significantly increased only for MMP-1 and decreased for MMP-8 and MMP-9. Conclusions: Taken together, these unique data demonstrate differential plasma profiles of MMPs, TIMPs, and miRs in ascending TAA specimens from patients with BAV and TAV. These results suggest that circulating biomarkers may form the foundation for a broader platform of biomarkers capable of detecting the presence of TAA using a simple blood test and may also be useful in personalized strategies to distinguish between etiologic subtypes of TAAs in patients with aneurysm disease. (J Thorac Cardiovasc Surg 2013; 145:1326-33) C1 [Ikonomidis, John S.; Ivey, Charlotte R.; Wheeler, Jason B.; Akerman, Adam W.; Rice, Allison; Patel, Risha K.; Stroud, Robert E.; Mukherjee, Rupak; Jones, Jeffrey A.] Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Shah, Asad A.; Hughes, Chad G.] Duke Univ, Sch Med, Dept Surg, Div Cardiothorac Surg, Durham, NC USA. [Ferrari, Giovanni] Univ Penn, Sch Med, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Jones, Jeffrey A.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, 25 Courtenay Dr,Suite 7030, Charleston, SC 29425 USA. EM ikonomij@musc.edu FU National Institutes of Health/National Institute on Aging [AG036954]; National Institutes of Health/National Heart, Lung, and Blood Institute [HL102121]; Veterans Affairs Merit Award [1 I01 BX000904-01] FX This study was supported by the following grants: National Institutes of Health/National Institute on Aging No. AG036954, National Institutes of Health/National Heart, Lung, and Blood Institute No. HL102121, and Veterans Affairs Merit Award No. 1 I01 BX000904-01. NR 20 TC 20 Z9 21 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2013 VL 145 IS 5 BP 1326 EP 1333 DI 10.1016/j.jtcvs.2012.12.027 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 129LJ UT WOS:000317840600029 PM 23312977 ER PT J AU Backhus, LM Hayanga, AJ Au, D Zeliadt, SB AF Backhus, Leah M. Hayanga, Awori J. Au, David Zeliadt, Steven B. TI The Effect of Provider Density on Lung Cancer Survival Among Blacks and Whites in the United States SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Racial disparities; Provider density ID PROSTATE-CANCER; GEOGRAPHIC ACCESS; NORTHERN ENGLAND; HEALTH-CARE; TRAVEL-TIME; BREAST; DISPARITIES; MORTALITY; SURGERY; RACE AB Introduction: Lung cancer mortality rates may vary with access to specialty providers and local resources. We sought to examine the effect of access to care, using density of lung cancer care providers, on lung cancer mortality among blacks and whites in the United States. Methods: We examined U.S. county-level data for age-adjusted lung cancer mortality rates from 2003 to 2007. Our primary independent variable was per capita number of thoracic oncologic providers, adjusting for county-level smoking rates, socioeconomic status, and other geographic factors. Data were obtained from 2009 Area Resource File, National Center for Health Statistics, and the County Health Rankings Project. Results: Providers of lung cancer care were unevenly distributed among the U.S. counties. For example, 41.4% of the U.S. population reside in counties with less than four thoracic surgeons per 100,000 people, 23.4% in counties with 4 to 15 surgeons per 100,000 people, and 35.3% in counties with more than 15 surgeons per 100,000 people. Geographically, 4.3% of whites compared with 11.2% of blacks lived in high lung cancer mortality zones. Lung cancer mortality did not vary by density of thoracic surgeons or oncology services; however, higher primary care provider density was associated with lung cancer mortality reduction of 4.1 per 100,000 for whites. Conclusion: Variation in provider density for thoracic oncology in the United States was not associated with a difference in lung cancer mortality. Lower mortality associated with higher primary care provider density suggests that equitable access to primary care may lead to reduced cancer disparities. C1 [Backhus, Leah M.; Au, David; Zeliadt, Steven B.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Backhus, Leah M.; Hayanga, Awori J.] Univ Washington, Div Cardiothorac Surg, Seattle, WA 98195 USA. [Au, David] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Au, David; Zeliadt, Steven B.] VA Hlth Serv Res & Dev Serv, Seattle, WA USA. RP Backhus, LM (reprint author), Univ Washington, Div Cardiothorac Surg, 1959 NE Pacific St,Suite 356310, Seattle, WA 98195 USA. EM lbackhus@u.washington.edu OI Backhus, Leah/0000-0002-4553-1003 NR 20 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2013 VL 8 IS 5 BP 549 EP 553 DI 10.1097/JTO.0b013e318287c24c PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 125ZX UT WOS:000317582000017 PM 23446202 ER PT J AU Conte, MS Owens, CD Belkin, M Creager, MA Edwards, KL Gasper, WJ Kenagy, RD LeBoeuf, RC Sobel, M Clowes, A AF Conte, Michael S. Owens, Christopher D. Belkin, Michael Creager, Mark A. Edwards, Karen L. Gasper, Warren J. Kenagy, Richard D. LeBoeuf, Renee C. Sobel, Michael Clowes, Alexander TI A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY JUN 16-18, 2011 CL Chicago, IL SP Soc Vasc Surg (SVS) ID DEPENDENT KINASE INHIBITORS; SMOOTH-MUSCLE-CELLS; PROMOTER ACTIVITY; VASCULAR-DISEASE; PREVENT-III; SURGERY; ARTERY; FAILURE; TRIAL; EDIFOLIGIDE AB Objective: Factors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27(Kip1) gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency. Methods: This was a retrospective genetic association study nested within a prospective cohort of 204 patients from three referral centers undergoing LEVBG for claudication or critical ischemia. The main outcome measure was primary vein graft patency. Results: All patients were followed up for a minimum of 1 year with duplex graft surveillance (median follow-up, 893 days; interquartile range, 539-1315). Genomic DNA was isolated and SNP analysis for the p27(Kip1)-838C>A variants was performed. Allele frequencies were correlated with graft outcome using survival analysis and Cox proportional hazards modeling. The p27(Kip1)-838C>A allele frequencies observed were CA, 53%; CC, 30%; and AA, 17%, satisfying Hardy-Weinberg equilibrium. Race (P = .025) and history of coronary artery disease (P = .027) were different across the genotypes; all other baseline variables were similar. Primary graft patency was greater among patients with the -838AA genotype (75% AA vs 55% CA/CC at 3 years; P = .029). In a Cox proportional hazards model including age, sex, race, diabetes, critical limb ischemia, redo (vs primary) bypass, vein type, and baseline C-reactive protein level, the p27(Kip1)-838AA genotype was significantly associated with higher graft patency (hazard ratio for failure, 0.4; 95% confidence interval, 0.17-0.93). Genotype was also associated with early (0-1 month) changes in graft lumen diameter by ultrasound imaging. Conclusions: These data suggest that the p27(Kip1)-838C>A SNP is associated with LEVBG patency and, together with previous reports, underscore a central role for p27(Kip1) in the generic response to vascular injury. (J Vasc Surg 2013;57:1179-85.) C1 [Conte, Michael S.; Owens, Christopher D.; Gasper, Warren J.] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Belkin, Michael] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Creager, Mark A.; Sobel, Michael] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Edwards, Karen L.] Univ Washington, Dept Epidemiol, Inst Publ Hlth Genet, Seattle, WA 98195 USA. [Kenagy, Richard D.; Clowes, Alexander] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [LeBoeuf, Renee C.] Univ Washington, Dept Med, Seattle, WA USA. [Sobel, Michael] Univ Washington, Div Vasc Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Conte, MS (reprint author), Univ Calif San Francisco, Heart & Vasc Ctr, Div Vasc & Endovasc Surg, 400 Parnassus Ave, San Francisco, CA 94143 USA. EM michael.conte@ucsfmedctr.org FU CSRD VA [I01 CX000712]; NHLBI NIH HHS [R01 HL098227, HL098227, HL30946, HL75771, R01 HL030946, R01 HL075771]; NIDDK NIH HHS [P30 DK017047] NR 32 TC 9 Z9 12 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 BP 1179 EP + DI 10.1016/j.jvs.2012.11.040 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 127RS UT WOS:000317716700001 PM 23312942 ER PT J AU Kougias, P Orcutt, S Pak, T Pisimisis, G Barshes, NR Lin, PH Bechara, CF AF Kougias, Panos Orcutt, Sonia Pak, Taemee Pisimisis, George Barshes, Neal R. Lin, Peter H. Bechara, Carlos F. TI Impact of postoperative nadir hemoglobin and blood transfusion on outcomes after operations for atherosclerotic vascular disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT William J. Von Liebig Forum at the Rapid Session of the Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) / Peripheral-Vascular-Surgery-Society Session CY JUN 07-09, 2012 CL National Harbor, MD SP Soc Vasc Surg (SVS), Peripheral Vasc Surg Soc ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-PRACTICE GUIDELINE; ACUTE CORONARY SYNDROMES; CELL TRANSFUSION; RESTRICTIVE TRANSFUSION; NONCARDIAC SURGERY; CARDIAC-SURGERY; CRITICAL-CARE; TRIAL; REQUIREMENTS AB Objective: Controversy surrounds the topic of transfusion policy after noncardiac operations. This study assessed the combined impact of postoperative nadir hemoglobin (nHb) levels and blood transfusion on adverse events after open surgical intervention in patients who undergo operative intervention for atherosclerotic vascular disease. Methods: Consecutive patients who underwent peripheral arterial disease (PAD)-related operations were balanced on baseline characteristics by inverse weighting on propensity score calculated as their probability to have nHb greater than 10 gm/dL on the basis of operation type, demographics, and comorbidities, including the revised cardiac risk index. A multivariate generalized estimating equation analysis was performed to investigate associations between nHb, transfusion, and a composite outcome of perioperative death and myocardial infarction. Logistic and Cox proportional hazards regressions were used to assess the impact of nHb and transfusion on respiratory and wound complications; and a composite end point (CE) of death, myocardial infarction during a 2-year follow-up. Level of statistical significance was set at alpha of 0.0125 to adjust for the increased probability of type I error attributable to multiple comparisons. Results: The analysis cohort included 880 patients (1074 operations). After adjusting for nHb level, the number of units transfused was not associated with the perioperative occurrence of the CE(odds ratio[OR], 1.13; P = .025). Adjusted for the number of units transfused, nHb had no impact on the perioperative CE (OR, 0.62; P = .22). An interaction term between transfusion and nHb level remained nonsignificant (P = .312), indicating that the impact of blood transfusion was the same regardless of the nHb level. Perioperative respiratory complications were more likely in patients receiving transfusions (OR, 1.22; P = .009), and perioperative wound infections were less common in patients with nHb > 10 gm/dL (OR, 0.65; P = .01). During an average follow-up of 24 months, transfused patients were more likely to develop the CE (hazard ratio [HR], 1.15, P = .009), whereas nHb level did not impact the long-term adverse event rate (HR, 0.78; P = .373). The above associations persisted even after adjusting the Cox regression model for the occurrence of perioperative cardiac events. Conclusions: Although nHb less than 10 gm/dL is not associated with death or ACS after PAD-related operations, maintaining nHb greater than 10 gm/dL appears to decrease the risk of wound infection. Blood transfusion is associated with increased risk of perioperative respiratory complications. Until a randomized trial settles this issue definitively, a restrictive transfusion strategy is justified in patients undergoing operations for atherosclerotic vascular disease. (J Vasc Surg 2013;57:1331-7.) C1 [Kougias, Panos; Pisimisis, George; Barshes, Neal R.; Bechara, Carlos F.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kougias, Panos; Orcutt, Sonia; Pak, Taemee; Pisimisis, George; Barshes, Neal R.; Lin, Peter H.; Bechara, Carlos F.] Baylor Coll Med, Houston, TX 77030 USA. RP Kougias, P (reprint author), Houston VAMC, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM pkougias@bcm.edu NR 33 TC 3 Z9 3 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 BP 1331 EP 1337 DI 10.1016/j.jvs.2012.10.108 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 127RS UT WOS:000317716700026 PM 23384496 ER PT J AU Brown, JR AF Brown, Jennifer R. TI Gastric mucosa-associated lymphoid tissue lymphoma resistant to Helicobacter pylori eradication: what's the best option? SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID MALT LYMPHOMA; T(11/18); THERAPY C1 [Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Brown, Jennifer R.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Brown, JR (reprint author), Harvard Univ, Sch Med, CLL Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM jbrown2@partners.org NR 11 TC 0 Z9 0 U1 0 U2 3 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 MAY PY 2013 VL 54 IS 5 BP 899 EP 900 DI 10.3109/10428194.2012.746686 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 126ZJ UT WOS:000317661900001 PM 23127114 ER PT J AU Jacobo, SMP DeAngelis, MM Kim, IK Kazlauskas, A AF Jacobo, Sarah Melissa P. DeAngelis, Margaret M. Kim, Ivana K. Kazlauskas, Andrius TI Age-Related Macular Degeneration-Associated Silent Polymorphisms in HtrA1 Impair Its Ability To Antagonize Insulin-Like Growth Factor 1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; VASCULAR ENDOTHELIAL-CELLS; FACTOR BINDING PROTEIN-5; SERINE-PROTEASE HTRA1; PULSE PROTEOLYSIS; MESSENGER-RNA; FACTOR-I; CHOROIDAL NEOVASCULARIZATION; NASCENT POLYPEPTIDE; SECONDARY STRUCTURE AB Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD. C1 [Jacobo, Sarah Melissa P.; Kazlauskas, Andrius] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Jacobo, Sarah Melissa P.; Kazlauskas, Andrius] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [DeAngelis, Margaret M.] Univ Utah, John A Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA. [Kim, Ivana K.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Kazlauskas, A (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. EM andrius_kazlauskas@meei.harvard.edu RI DeAngelis, e/J-7863-2015; OI Jacobo, Sarah Melissa/0000-0002-1341-7222 FU AMD Center for Excellence; Thome Memorial Foundation Bank of America; [EY014458] FX The AMD Center for Excellence provided support for this project, as did EY014458 and Thome Memorial Foundation Bank of America grants to M.M.D. NR 80 TC 8 Z9 8 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2013 VL 33 IS 10 BP 1976 EP 1990 DI 10.1128/MCB.01283-12 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130ZN UT WOS:000317959900009 PM 23478260 ER PT J AU Sheth, SA Eckhardt, CA Walcott, BP Eskandar, EN Simon, MV AF Sheth, Sameer A. Eckhardt, Christine A. Walcott, Brian P. Eskandar, Emad N. Simon, Mirela V. TI Factors Affecting Successful Localization of the Central Sulcus Using the Somatosensory Evoked Potential Phase Reversal Technique SO NEUROSURGERY LA English DT Article DE Brain neoplasms; Cerebral cortex; Electrophysiology; Intraoperative; Monitoring; Neurosurgery; Somatosensory evoked potentials ID SENSORIMOTOR CORTEX; PRECENTRAL GYRUS; BRAIN PLASTICITY; FUNCTIONAL MRI; MOTOR CORTEX; SURGERY; TUMORS; SUPPRESSION; RESECTION; EPILEPSY AB BACKGROUND: Perirolandic surgery is associated with an increased risk of postoperative neurological deficit that can be reduced by accurate recognition of the location of sensorimotor cortex. The median somatosensory evoked potential (MSSEP) phase reversal technique (PRT) reliably identifies the central sulcus (CS) intraoperatively, but does require additional surgical time. Awareness of factors that lengthen the time required for MSSEP PRT has important implications for surgical planning. OBJECTIVE: To identify factors that affect the time required for CS localization via MSSEP PRT. METHODS: Multivariate Cox regression analysis, applied in 100 consecutive cases of perirolandic surgery at a single institution from 2005 to 2010, during which CS localization was attempted via a standardized MSSEP PRT. RESULTS: The CS was reliably identified in 77 cases. The mean time to identification was 5 minutes (SD=5; range, 1-20 minutes). Lesion location either very close to the CS (within the postcentral gyrus) or at an intermediate distance (with edema extending very close to the CS) independently decreased the rate at which the CS was identified by 73% (hazard ratio: 0.27, P<.001) and 55% (hazard ratio: 0.45, P=.007), respectively. Highly destructive pathology reduced this rate by 42% (hazard ratio: 0.58, P=.03), after adjusting for other important factors. Epidural recording, age, and the presence of a burst suppression pattern on the electroencephalogram had no effect. CONCLUSION: MSSEP PRT is an effective method for CS identification and only marginally lengthens the operative time. However, difficulty in CS localization can be expected in the presence of postcentral gyrus lesions, edema distorting perirolandic anatomy, and with highly destructive pathology. C1 [Sheth, Sameer A.; Eckhardt, Christine A.; Walcott, Brian P.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Simon, Mirela V.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Simon, Mirela V.] Harvard Univ, Sch Med, Boston, MA USA. RP Sheth, SA (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM sheth@post.harvard.edu NR 31 TC 4 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2013 VL 72 IS 5 BP 828 EP 834 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 130KS UT WOS:000317915100031 PM 23381491 ER PT J AU Geiser, DM Aoki, T Bacon, CW Baker, SE Bhattacharyya, MK Brandt, ME Brown, DW Burgess, LW Chulze, S Coleman, JJ Correll, JC Covert, SF Crous, PW Cuomo, CA De Hoog, GS Di Pietro, A Elmer, WH Epstein, L Frandsen, RJN Freeman, S Gagkaeva, T Glenn, AE Gordon, TR Gregory, NF Hammond-Kosack, KE Hanson, LE Jimenez-Gasco, MD Kang, S Kistler, HC Kuldau, GA Leslie, JF Logrieco, A Lu, GZ Lysoe, E Ma, LJ McCormick, SP Migheli, Q Moretti, A Munaut, F O'Donnell, K Pfenning, L Ploetz, RC Proctor, RH Rehner, SA Robert, VARG Rooney, AP bin Salleh, B Scandiani, MM Scauflaire, J Short, DPG Steenkamp, E Suga, H Summerell, BA Sutton, DA Thrane, U Trail, F Van Diepeningen, A VanEtten, HD Viljoen, A Waalwijk, C Ward, TJ Wingfield, MJ Xu, JR Yang, XB Yli-Mattila, T Zhang, N AF Geiser, David M. Aoki, Takayuki Bacon, Charles W. Baker, Scott E. Bhattacharyya, Madan K. Brandt, Mary E. Brown, Daren W. Burgess, Lester W. Chulze, Sofia Coleman, Jeffrey J. Correll, James C. Covert, Sarah F. Crous, Pedro W. Cuomo, Christina A. De Hoog, G. Sybren Di Pietro, Antonio Elmer, Wade H. Epstein, Lynn Frandsen, Rasmus J. N. Freeman, Stanley Gagkaeva, Tatiana Glenn, Anthony E. Gordon, Thomas R. Gregory, Nancy F. Hammond-Kosack, Kim E. Hanson, Linda E. Jimenez-Gasco, Maria del Mar Kang, Seogchan Kistler, H. Corby Kuldau, Gretchen A. Leslie, John F. Logrieco, Antonio Lu, Guozhong Lysoe, Erik Ma, Li-Jun McCormick, Susan P. Migheli, Quirico Moretti, Antonio Munaut, Francoise O'Donnell, Kerry Pfenning, Ludwig Ploetz, Randy C. Proctor, Robert H. Rehner, Stephen A. Robert, Vincent A. R. G. Rooney, Alejandro P. bin Salleh, Baharuddin Mercedes Scandiani, Maria Scauflaire, Jonathan Short, Dylan P. G. Steenkamp, Emma Suga, Haruhisa Summerell, Brett A. Sutton, Deanna A. Thrane, Ulf Trail, Francis Van Diepeningen, Anne VanEtten, Hans D. Viljoen, Altus Waalwijk, Cees Ward, Todd J. Wingfield, Michael J. Xu, Jin-Rong Yang, Xiao-Bing Yli-Mattila, Tapani Zhang, Ning TI One Fungus, One Name: Defining the Genus Fusarium in a Scientifically Robust Way That Preserves Longstanding Use SO PHYTOPATHOLOGY LA English DT Article ID SOLANI SPECIES COMPLEX; SUDDEN-DEATH SYNDROME; PHYLOGENY; TUCUMANIAE; TAXONOMY; REVEALS; GENERA AB In this letter, we advocate recognizing the genus Fusarium as the sole name for a group that includes virtually all Fusarium species of importance in plant pathology, mycotoxicology, medicine, and basic research. This phylogenetically guided circumscription will free scientists from any obligation to use other genus names, including teleomorphs, for species nested within this clade, and preserve the application of the name Fusarium in the way it has been used for almost a century. Due to recent changes in the International Code of Nomenclature for algae, fungi, and plants, this is an urgent matter that requires community attention. The alternative is to break the longstanding concept of Fusarittm into nine or more genera, and remove important taxa such as those in the E solani species complex from the genus, a move we believe is unnecessary. Here we present taxonomic and nomenclatural proposals that will preserve established research connections and facilitate communication within alid between research communities, and at the same time support strong scientific principles and good taxonomic practice. C1 [Geiser, David M.; Jimenez-Gasco, Maria del Mar; Kang, Seogchan; Kuldau, Gretchen A.] Penn State Univ, Dept Plant Pathol, University Pk, PA 16802 USA. [Aoki, Takayuki] Natl Inst Agrobiol Sci, Genet Divers Dept, Tsukuba, Ibaraki 3058602, Japan. [Bacon, Charles W.; Glenn, Anthony E.] USDA ARS SAA, Athens, GA 30605 USA. [Baker, Scott E.] Pacific NW Natl Lab, Richland, WA 99352 USA. [Bhattacharyya, Madan K.; Yang, Xiao-Bing] Iowa State Univ, Dept Plant Pathol & Microbiol, Ames, IA 50011 USA. [Brandt, Mary E.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Brown, Daren W.; McCormick, Susan P.; O'Donnell, Kerry; Proctor, Robert H.; Rooney, Alejandro P.; Ward, Todd J.] NCAUR ARS USDA, Peoria, IL 61604 USA. [Burgess, Lester W.] Univ Sydney, Fac Agr, Sydney, NSW 2006, Australia. [Chulze, Sofia] Univ Nacl Rio Cuarto, Dept Microbiol & Immunol, Cordoba, Argentina. [Coleman, Jeffrey J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Correll, James C.] Univ Arkansas, Dept Plant Pathol, Fayetteville, AR 72701 USA. [Covert, Sarah F.] Univ Georgia, Warnell Sch Forestry & Nat Resources, Athens, GA 30602 USA. [Crous, Pedro W.; De Hoog, G. Sybren; Robert, Vincent A. R. G.; Van Diepeningen, Anne] CBS KNAW Fungal Biodivers Ctr, Utrecht, Netherlands. [Cuomo, Christina A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Di Pietro, Antonio] Univ Cordoba, Dept Genet, Cordoba, Spain. [Elmer, Wade H.] Connecticut Agr Expt Stn, Dept Plant Pathol, New Haven, CT 06504 USA. [Epstein, Lynn; Gordon, Thomas R.; Short, Dylan P. G.] Univ Calif Davis, Dept Plant Pathol, Davis, CA 95616 USA. [Frandsen, Rasmus J. N.; Thrane, Ulf] Tech Univ Denmark, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Freeman, Stanley] Agr Res Org, Volcani Ctr, Dept Plant Pathol & Weed Res, IL-50250 Bet Dagan, Israel. [Gagkaeva, Tatiana] All Russian Inst Plant Protect, Lab Mycol & Phytopathol, St Petersburg 196608, Russia. [Gregory, Nancy F.] Univ Delaware, Dept Plant & Soil Sci, Newark, DE 19716 USA. [Hammond-Kosack, Kim E.] Rothamsted Res, Ctr Sustainable Pest & Dis Management, Harpenden AL5 2JQ, Herts, England. [Hanson, Linda E.] ARS USDA Sugarbeet & Bean Res Unit, E Lansing, MI 48824 USA. [Kistler, H. Corby] ARS USDA Cereal Dis Lab, St Paul, MN 55108 USA. [Leslie, John F.] Kansas State Univ, Dept Plant Pathol, Manhattan, KS 66506 USA. [Logrieco, Antonio; Moretti, Antonio] CNR, ISPA Inst Sci Food Prod, I-70126 Bari, Italy. [Lu, Guozhong] Dalian Nationalities Univ, Res Ctr Bioresources & Environm, Liaoning, Peoples R China. [Lysoe, Erik] Bioforsk Norwegian Inst Agr & Environm Res, Dept Plant Hlth & Plant Protect, N-1432 As, Norway. [Ma, Li-Jun] Univ Massachusetts, Dept Plant Soil & Insect Sci, Amherst, MA 01003 USA. [Migheli, Quirico] Univ Sassari, Dipartimento Protez Piante, I-07100 Sassari, Italy. [Munaut, Francoise; Scauflaire, Jonathan] Catholic Univ Louvain, Earth & Life Inst, B-1348 Louvain, Belgium. [Pfenning, Ludwig] Univ Fed Lavras, Dept Fitopatol, Lavras, MG, Brazil. [Ploetz, Randy C.] Univ Florida, Ctr Trop Res & Educ, Dept Plant Pathol, Homestead, FL 33031 USA. [Rehner, Stephen A.] ARS, Systemat Mycol & Microbiol Lab, USDA, Beltsville, MD 20705 USA. [bin Salleh, Baharuddin] Univ Sci Malaysia, Sch Biol Sci, George Town, Malaysia. [Mercedes Scandiani, Maria] Lab Agr Rio Parana, Buenos Aires, DF, Argentina. [Short, Dylan P. G.] US Agr Res Stn, Salinas, CA 93905 USA. [Steenkamp, Emma; Wingfield, Michael J.] Univ Pretoria, FABI, Dept Microbiol & Plant Pathol, ZA-0002 Pretoria, South Africa. [Suga, Haruhisa] Gifu Univ, Gifu, Japan. [Summerell, Brett A.] Royal Bot Garden Sydney, Sydney, NSW 2000, Australia. [Sutton, Deanna A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Trail, Francis] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA. [VanEtten, Hans D.] Univ Arizona, Div Plant Pathol & Microbiol, Tucson, AZ 85721 USA. [Viljoen, Altus] Univ Stellenbosch, Dept Plant Pathol, ZA-7602 Matieland, South Africa. [Waalwijk, Cees] Wageningen Univ & Res, Plant Res Int, NL-6700 Wageningen, Netherlands. [Xu, Jin-Rong] Purdue Univ, Dept Plant Pathol, W Lafayette, IN 47907 USA. [Yli-Mattila, Tapani] Univ Turku, Lab Plant Physiol & Mol Biol, Dept Biol, FIN-20014 Turku, Finland. [Zhang, Ning] Rutgers State Univ, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA. RP Geiser, DM (reprint author), Penn State Univ, Dept Plant Pathol, University Pk, PA 16802 USA. EM dgeiser@psu.edu RI Jimenez-Gasco, Maria del Mar/A-9701-2011; Migheli, Quirico/B-7203-2009; Crous, Pedro/H-1489-2012; Geiser, David/J-9950-2013; Zhang, Ning/K-3046-2012; Wingfield, Michael/A-9473-2008; Coleman, Jeffrey/E-2981-2015; Di Pietro, Antonio/K-9220-2014; Thrane, Ulf/G-2978-2016; Steenkamp, Emma/B-7958-2009; OI Frandsen, Rasmus John Normand/0000-0002-3799-6062; Moretti, Antonio/0000-0002-5232-6972; Logrieco, Antonio Francesco/0000-0002-8606-451X; Kistler, Harold/0000-0001-5312-6297; Kang, Seogchan/0000-0003-2291-5634; Jimenez-Gasco, Maria del Mar/0000-0001-7329-0211; Migheli, Quirico/0000-0002-2459-5833; Crous, Pedro/0000-0001-9085-8825; Zhang, Ning/0000-0003-0755-2505; Di Pietro, Antonio/0000-0001-5930-5763; Thrane, Ulf/0000-0002-6040-4141; Steenkamp, Emma/0000-0003-0217-8219; Ma, Li-Jun/0000-0002-2733-3708; Coleman, Jeffrey/0000-0001-8579-1996 FU U.S. Department of Agriculture (USDA) FX We thank P. Cantino for his helpful comments on the PhyloCode statement. We thank all of our colleagues for their helpful input and discussions on this important issue. The mention of firm names or trade products does not imply that they are endorsed or recommended by the U.S. Department of Agriculture (USDA) over other firms or similar products not mentioned. The USDA is an equal opportunity provider and employer. Manuscript no. 13-006-J from the Kansas Agricultural Experiment Station, Manhattan. NR 46 TC 47 Z9 48 U1 5 U2 114 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD MAY PY 2013 VL 103 IS 5 BP 400 EP 408 PG 9 WC Plant Sciences SC Plant Sciences GA 129VW UT WOS:000317873100001 PM 23379853 ER PT J AU Fukumoto, T Kano, A Ohtani, K Inoue, M Yoshihara, A Izumori, K Tajima, S Shigematsu, Y Tanaka, K Ohkouchi, T Ishida, Y Nishizawa, Y Tada, Y Ichimura, K Gomi, K Yoo, SD Sheen, J Akimitsu, K AF Fukumoto, Takeshi Kano, Akihito Ohtani, Kouhei Inoue, Megumi Yoshihara, Akihide Izumori, Ken Tajima, Shigeyuki Shigematsu, Yoshio Tanaka, Keiji Ohkouchi, Takeo Ishida, Yutaka Nishizawa, Yoko Tada, Yasuomi Ichimura, Kazuya Gomi, Kenji Yoo, Sang-Dong Sheen, Jen Akimitsu, Kazuya TI Phosphorylation of D-allose by hexokinase involved in regulation of OsABF1 expression for growth inhibition in Oryza sativa L. SO PLANTA LA English DT Article DE Abscisic acid; D-Allose; AtABI5; Hexokinase; OsABF1 ID DEFENSE-RELATED GENES; ABSCISIC-ACID; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; ABA 8'-HYDROXYLASE; RESPONSE PATHWAYS; BACTERIAL-BLIGHT; PROTEIN-KINASES; HIGHER-PLANTS; UP-REGULATION AB We previously reported that a rare sugar d-allose, which is the d-glucose epimer at C3, inhibits the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of alpha-amylase in embryo-less half seeds in rice (Fukumoto et al. 2011). d-Allose suppresses expressions of gibberellin-responsive genes downstream of SLR1 protein in the gibberellin-signaling through hexokinase (HXK)-dependent pathway. In this study, we discovered that d-allose induced expression of ABA-related genes including OsNCED1-3 and OsABA8ox1-3 in rice. Interestingly, d-allose also up-regulated expression of OsABF1, encoding a conserved bZIP transcription factor in ABA signaling, in rice. The d-allose-induced expression of OsABF1 was diminished by a hexokinase inhibitor, d-mannoheptulose (MNH). Consistently, d-allose also inhibited Arabidopsis growth, but failed to trigger growth retardation in the glucose-insensitive2 (gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1. d-Allose activated AtABI5 expression in transgenic gin2 over-expressing wild-type AtHXK1 but not in gin2 over-expressing the catalytic mutant AtHXK1(S177A), indicating that the d-allose phosphorylation by HXK to d-allose 6-phosphate (A6P) is the first step for the up-regulation of AtABI5 gene expression as well as d-allose-induced growth inhibition. Moreover, overexpression of OsABF1 showed increased sensitivity to d-allose in rice. These findings indicated that the phosphorylation of d-allose at C6 by hexokinase is essential and OsABF1 is involved in the signal transduction for d-allose-induced growth inhibition. C1 [Fukumoto, Takeshi; Kano, Akihito; Ohtani, Kouhei; Inoue, Megumi; Yoshihara, Akihide; Izumori, Ken; Tajima, Shigeyuki; Tada, Yasuomi; Ichimura, Kazuya; Gomi, Kenji; Akimitsu, Kazuya] Kagawa Univ, Fac Agr, Rare Sugar Res Ctr, Miki, Kagawa 7610795, Japan. [Fukumoto, Takeshi; Kano, Akihito; Ohtani, Kouhei; Inoue, Megumi; Yoshihara, Akihide; Izumori, Ken; Tajima, Shigeyuki; Tada, Yasuomi; Ichimura, Kazuya; Gomi, Kenji; Akimitsu, Kazuya] Kagawa Univ, Ctr Gene Res, Miki, Kagawa 7610795, Japan. [Shigematsu, Yoshio; Tanaka, Keiji; Ohkouchi, Takeo] Mitsui Chem Agro Co Ltd, Yasu, Shiga 5202342, Japan. [Ishida, Yutaka] Shikoku Res Inst Inc, Takamatsu, Kagawa 7610192, Japan. [Nishizawa, Yoko] Natl Inst Agrobiol Sci, Tsukuba, Ibaragi 3058602, Japan. [Yoo, Sang-Dong] Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea. [Sheen, Jen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Akimitsu, K (reprint author), Kagawa Univ, Fac Agr, Rare Sugar Res Ctr, Miki, Kagawa 7610795, Japan. EM kazuya@ag.kagawa-u.ac.jp RI Tada, Yasuomi/M-5041-2014; OI Tada, Yasuomi/0000-0001-9900-069X FU Programme for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry FX We thank Rice Genome Resource Center at National Institute of Agrobiological Sciences (NIAS, Tsukuba, Japan) for providing full-length cDNA used in this study. This study was supported by the Programme for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry. NR 54 TC 9 Z9 9 U1 3 U2 44 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0032-0935 J9 PLANTA JI Planta PD MAY PY 2013 VL 237 IS 5 BP 1379 EP 1391 DI 10.1007/s00425-013-1853-9 PG 13 WC Plant Sciences SC Plant Sciences GA 134BZ UT WOS:000318186000016 PM 23397192 ER PT J AU Penney, KL Li, HJ Mucci, LA Loda, M Sesso, HD Stampfer, MJ Ma, J AF Penney, Kathryn L. Li, Haojie Mucci, Lorelei A. Loda, Massimo Sesso, Howard D. Stampfer, Meir J. Ma, Jing TI Selenoprotein P genetic variants and mrna expression, circulating selenium, and prostate cancer risk and survival SO PROSTATE LA English DT Article DE genetic variation; selenium; prostate cancer ID POLYMORPHISM; PREVENTION; TRIAL; SUPPLEMENTATION AB BACKGROUND Low levels of selenium have been associated with increased risk of prostate cancer (PCa). Selenoprotein P is the most abundant selenoprotein in serum and delivers ten selenocysteine residues to tissues. Variation in the selenoprotein P gene (SEPP1) may influence PCa development or modify the effects of selenium. We examined the association of SEPP1 single nucleotide polymorphisms (SNPs) with PCa risk and survival, and tested for interactions. METHODS The Physicians' Health Study (PHS) is a prospective cohort of 22,071 US physicians; we utilized a nested casecontrol study of 1,352 PCa cases and 1,382 controls. We assessed four SNPs capturing common variation within the SEPP1 locus. In a subset of men (n=80), we evaluated SEPP1 mRNA expression in tumors. RESULTS Two SNPs were significantly associated with PCa risk. For rs11959466, each T allele increased risk (odds ratio (OR)=1.31; 95% confidence interval (CI): 1.02,1.69; Ptrend=0.03). For rs13168440, the rare homozygote genotype decreased risk compared to the common homozygote (OR=0.56, 95% CI: 0.33, 0.96). Moreover, there was a significant interaction of rs13168440 with plasma selenium; increasing selenium levels were associated with decreased PCa risk only among men with the minor allele (Pinteraction=0.01). SEPP1 expression was significantly lower in men with lethal PCa than long-term survivors. CONCLUSIONS SEPP1 genetic variation was associated with PCa incidence; replication of these results in an independent dataset is necessary. These findings further support a causal link between selenium and PCa, and suggest that the effect of selenium may differ by genetics. Prostate 73: 700705, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Penney, Kathryn L.; Mucci, Lorelei A.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Penney, Kathryn L.; Mucci, Lorelei A.; Stampfer, Meir J.; Ma, Jing] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Penney, Kathryn L.; Mucci, Lorelei A.; Loda, Massimo; Sesso, Howard D.; Stampfer, Meir J.; Ma, Jing] Harvard Univ, Sch Med, Boston, MA USA. [Li, Haojie] GlaxoSmithKline R&D, Worldwide Epidemiol Oncol, Collegeville, PA USA. [Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med & Aging, Boston, MA 02115 USA. RP Penney, KL (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM kpenney@hsph.harvard.edu; jing.ma@channing.harvard.edu FU Department of Defense [PC073618, PC050569]; National Cancer Institute [CA42182, CA34944, CA40360, CA141298, CA097193]; National Heart, Lung, and Blood Institute, Bethesda, Maryland [HL26490, HL34595]; Prostate Cancer Foundation; National Research Service Award [T32 CA009001] FX Grant sponsor: Department of Defense; Grant numbers: PC073618, PC050569; Grant sponsor: National Cancer Institute; Grant numbers: CA42182, CA34944, CA40360, CA141298, CA097193; Grant sponsor: National Heart, Lung, and Blood Institute, Bethesda, Maryland; Grant numbers: HL26490, HL34595; Grant sponsor: Prostate Cancer Foundation; Grant sponsor: National Research Service Award; Grant number: T32 CA009001. NR 22 TC 11 Z9 16 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY PY 2013 VL 73 IS 7 BP 700 EP 705 DI 10.1002/pros.22611 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 130PL UT WOS:000317930600003 PM 23129481 ER PT J AU Prencipe, M Madden, SF O'Neill, A O'Hurley, G Culhane, A O'Connor, D Klocker, H Kay, EW Gallagher, WM Watson, WR AF Prencipe, Maria Madden, Stephen F. O'Neill, Amanda O'Hurley, Gillian Culhane, Aedin O'Connor, Darran Klocker, Helmut Kay, Elaine W. Gallagher, William M. Watson, William R. TI Identification of transcription factors associated with castration-resistance: Is the serum responsive factor a potential therapeutic target? SO PROSTATE LA English DT Article DE advanced prostate cancer; transcription-factors prediction analysis; serum response factor (SRF) ID INDEPENDENT PROSTATE-CANCER; CO-INERTIA ANALYSIS; TUMOR-GROWTH; GENE; OLIGONUCLEOTIDE; PROLIFERATION; PROGRESSION; MECHANISMS; REGULATOR; DISCOVERY AB BACKGROUND Advanced prostate cancer is treated by hormone ablation therapy. However, despite an initial response, the majority of men relapse to develop castration-resistant disease for which there are no effective treatments. We have previously shown that manipulating individual proteins has only minor alterations on the resistant phenotype so we hypothesize that targeting the central transcription factors (TFs) would represent a better therapeutic approach. METHODS We have undertaken a transcriptomic analysis of gene expression differences between the androgen-dependent LNCaP parental cells and its castration-resistant Abl and Hof sublines, revealing 1,660 genes associated with castration-resistance. Using effective bioinformatic techniques, these transcriptomic data were integrated with TF binding sites resulting in a list of TFs associated with the differential gene expression observed. RESULTS Following validation of the gene-chip results, the serum response factor (SRF) was chosen for clinical validation and functional analysis due to its recent association with prostate cancer progression. SRF immunoreactivity in prostate tumor samples was shown for the first time to be associated with castration-resistance. SRF inhibition by siRNA and the small molecule inhibitor CCG-1423 resulted in decreased proliferation. CONCLUSION SRF is a key TF by which resistant cells survive with depleted levels of androgens representing a target for therapeutic manipulation. Prostate 73: 743753, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Prencipe, Maria; O'Neill, Amanda; Watson, William R.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, UCD Sch Med & Med Sci, Dublin 2, Ireland. [Madden, Stephen F.] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland. [O'Hurley, Gillian; Gallagher, William M.] OncoMark Ltd, NovaUCD, Dublin, Ireland. [Culhane, Aedin] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [O'Connor, Darran; Gallagher, William M.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, UCD Sch Biomol & Biomed Sci, Dublin 2, Ireland. [Klocker, Helmut] Med Univ Innsbruck, Dept Urol, A-6020 Innsbruck, Austria. [Kay, Elaine W.] Beaumont Hosp, Dept Pathol, RCSI Educ & Res Ctr, Dublin 9, Ireland. RP Prencipe, M (reprint author), Univ Coll Dublin, Conway Inst Biomol & Biomed Res, UCD Sch Med & Med Sci, D4, Dublin 2, Ireland. EM maria.prencipe@ucd.ie RI Kay, Elaine/D-8539-2013; OI Gallagher, William/0000-0002-4307-5999 FU Science Foundation Ireland Strategic Research Cluster; Molecular Therapeutics for Cancer Ireland; FP7 Marie Curie Industry-Academia Partnership and Pathways Program (FAST-PATH) FX Grant sponsor: Science Foundation Ireland Strategic Research Cluster; Grant sponsor: Molecular Therapeutics for Cancer Ireland; Grant sponsor: FP7 Marie Curie Industry-Academia Partnership and Pathways Program (FAST-PATH). NR 43 TC 10 Z9 11 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY PY 2013 VL 73 IS 7 BP 743 EP 753 DI 10.1002/pros.22618 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 130PL UT WOS:000317930600008 PM 23359479 ER PT J AU Theall, KP Brett, ZH Shirtcliff, EA Dunn, EC Drury, SS AF Theall, Katherine P. Brett, Zoe H. Shirtcliff, Elizabeth A. Dunn, Erin C. Drury, Stacy S. TI Neighborhood disorder and telomeres: Connecting children's exposure to community level stress and cellular response SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Neighborhood; Children; Telomere; Stress; Average telomere length ID BIOLOGICAL RISK PROFILES; CORONARY HEART-DISEASE; ALLOSTATIC LOAD; SOCIOECONOMIC-STATUS; EARLY-CHILDHOOD; US ADULTS; RESIDENTIAL PREFERENCES; CARDIOVASCULAR RISK; PHYSICAL-ACTIVITY; CUMULATIVE RISK AB Our objective was to explore the utility of salivary telomere length (sTL) as an early indicator of neighborhood-level social environmental risk during child development. We therefore tested the hypothesis that sTL would be associated with markers of social stress exposure in children. Children age 4-14 from 87 neighborhoods were recruited through five urban schools in New Orleans, Louisiana, U.S. Data were collected at the level of the child, family/household, and neighborhood. DNA was obtained from saliva using commercially available kits and sTL was determined for 104 children using quantitative PCR. Analysis was performed on 99 children who had complete data including sTL, social environmental stress, and additional covariates. The mean sTL value was 7.4 T/S (telomere signal/single-copy signal) ratio units (+/- 2.4, range = 2.5-18.0), and 4.7% of the variance in sTL was attributed to differences across neighborhoods. Children living in neighborhoods characterized by high disorder had an sTL value 3.2 units lower than children not living in high disordered environments (p < 0.05) and their odds of having low relative sTL (defined as <1 standard deviation below standardized Z-score mean) values was 3.43 times that of children not living in high disorder environments (adjusted OR = 3.43, 95% CI = 1.22, 9.62). Our findings are consistent with previous studies in adults demonstrating a strong link between psychosocial stress and sTL obtained from peripheral blood, consistent with previous studies in youth demonstrating an association between early life stress and sTL obtained from buccal cell DNA and offer increased support for the hypothesis that sTL represents a non-invasive biological indicator of psychosocial stress exposure (i.e., neighborhood disorder) able to reflect differences in stress exposure levels even in young children. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Theall, Katherine P.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Community Hlth & Behav Sci, New Orleans, LA 70112 USA. [Brett, Zoe H.; Drury, Stacy S.] Tulane Univ, Sch Med, Dept Psychiat & Behav Sci, New Orleans, LA 70112 USA. [Shirtcliff, Elizabeth A.] Univ New Orleans, Dept Psychol, New Orleans, LA 70148 USA. [Dunn, Erin C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Theall, KP (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Community Hlth & Behav Sci, 1440 Canal St,Suite 2301, New Orleans, LA 70112 USA. EM ktheall@tulane.edu FU Centers for Disease Control and Prevention, CDC [1K01SH000002]; National Institutes of Health, NIH [1R01ES020447-01, R21 MH094688-01, 1R01MH091363, K01-MH077687]; Tulane University (CTREC) FX This study was supported by grants from the Centers for Disease Control and Prevention, CDC (1K01SH000002 to K.P.T.), the National Institutes of Health, NIH (1R01ES020447-01 to K.P.T., R21 MH094688-01 to SSD, 1R01MH091363 (Nelson) for ZB, and K01-MH077687 to E.A.S.), and Tulane University (CTREC to S.D.). This study was approved by the Tulane and Louisiana State University Institutional Review Boards. The authors thank Jeanette Magnus, Richard Scribner, Emily Mabile and Immaculata De Vivo. There are no conflicts of interest to report. We are indebted to the parents of the subjects for their cooperation and their permission for their children to participate in the study. NR 90 TC 43 Z9 43 U1 5 U2 45 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAY PY 2013 VL 85 BP 50 EP 58 DI 10.1016/j.socscimed.2013.02.030 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 129YQ UT WOS:000317880300008 PM 23540366 ER PT J AU Arikatla, VS Sankaranarayanan, G Ahn, W Chellali, A De, S Caroline, GL Hwabejire, J DeMoya, M Schwaitzberg, S Jones, DB AF Arikatla, Venkata S. Sankaranarayanan, Ganesh Ahn, Woojin Chellali, Amine De, Suvranu Caroline, G. L. Hwabejire, John DeMoya, Marc Schwaitzberg, Steven Jones, Daniel B. TI Face and construct validation of a virtual peg transfer simulator SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Virtual reality; Surgical training; Face validity; Construct; Laparoscopy; Length of trajectory ID LAPAROSCOPIC SKILLS; SURGICAL SIMULATION; PERFORMANCE; VALIDITY; SURGERY; SYSTEM; FLS AB The Fundamentals of Laparoscopic Surgery (FLS) trainer box is now established as a standard for evaluating minimally invasive surgical skills. A particularly simple task in this trainer box is the peg transfer task which is aimed at testing the surgeon's bimanual dexterity, hand-eye coordination, speed, and precision. The Virtual Basic Laparoscopic Skill Trainer (VBLaSTA (c)) is a virtual version of the FLS tasks which allows automatic scoring and real-time, subjective quantification of performance without the need of a human proctor. In this article we report validation studies of the VBLaSTA (c) peg transfer (VBLaST-PTA (c)) simulator. Thirty-five subjects with medical background were divided into two groups: experts (PGY 4-5, fellows, and practicing surgeons) and novices (PGY 1-3). The subjects were asked to perform the peg transfer task on both the FLS trainer box and the VBLaST-PTA (c) simulator; their performance was evaluated based on established metrics of error and time. A new length of trajectory (LOT) metric has also been introduced for offline analysis. A questionnaire was used to rate the realism of the virtual system on a 5-point Likert scale. Preliminary face validation of the VBLaST-PTA (c) with 34 subjects rated on a 5-point Likert scale questionnaire revealed high scores for all aspects of simulation, with 3.53 being the lowest mean score across all questions. A two-tailed Mann-Whitney test performed on the total scores showed significant (p = 0.001) difference between the groups. A similar test performed on the task time (p = 0.002) and the LOT (p = 0.004) separately showed statistically significant differences between the experts and the novices (p < 0.05). The experts appear to be traversing shorter overall trajectories in less time than the novices. VBLaST-PTA (c) showed both face and construct validity and has promise as a substitute for the FLS for training peg transfer skills. C1 [Arikatla, Venkata S.; Sankaranarayanan, Ganesh; Ahn, Woojin; De, Suvranu] Rensselaer Polytech Inst, Ctr Modeling Simulat & Imaging Med, Troy, NY 12180 USA. [Chellali, Amine; Schwaitzberg, Steven] Harvard Univ, Sch Med, Dept Surg, Cambridge Hlth Alliance, Boston, MA 02115 USA. [De, Suvranu] Rensselaer Polytech Inst, Dept Mech Aerosp & Nucl Engn, Troy, NY 12180 USA. [Caroline, G. L.] Wright State Univ, Dept Biomed Ind & Human Factors Engn, Fairborn, OH USA. [Hwabejire, John; DeMoya, Marc] Harvard Univ, Massachusetts Gen Hosp, Div Trauma, Boston, MA 02115 USA. [Jones, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. RP Arikatla, VS (reprint author), Rensselaer Polytech Inst, Ctr Modeling Simulat & Imaging Med, Troy, NY 12180 USA. EM arikav@rpi.edu; des@rpi.edu FU NIH/NIBIB [5R01EB010037] FX The authors gratefully acknowledge the support of this study by NIH/NIBIB (Grant No. 5R01EB010037). They also thank Alex Derevianko of Massachusetts General Hospital (MGH) for helping conduct the experiments and Saurabh Dargar of Rensselaer Polytechnic Institute for helping during the hardware design phase. NR 24 TC 9 Z9 9 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAY PY 2013 VL 27 IS 5 BP 1721 EP 1729 DI 10.1007/s00464-012-2664-y PG 9 WC Surgery SC Surgery GA 129PG UT WOS:000317853100037 PM 23263645 ER PT J AU Meireles, OR Horgan, S Jacobsen, GR Katagiri, T Mathew, A Sedrak, M Sandler, BJ Dotai, T Savides, TJ Majid, SF Nijhawan, S Talamini, MA AF Meireles, Ozanan R. Horgan, Santiago Jacobsen, Garth R. Katagiri, Toshio Mathew, Abraham Sedrak, Michael Sandler, Bryan J. Dotai, Takayuki Savides, Thomas J. Majid, Saniea F. Nijhawan, Sheetal Talamini, Mark A. TI Transesophageal endoscopic myotomy (TEEM) for the treatment of achalasia: the United States human experience SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE POEM; TEEM; Myotomy; Achalasia; NOTES; Endoscopic ID ESOPHAGEAL ACHALASIA; SURGERY AB From our early experience with NOTES, our group has acquired familiarity with transesophageal submucosal dissection and myotomy in swine model, which allowed us to perfect a model to perform purely endoscopic transesophageal myotomy (TEEM) for the treatment of achalasia and apply it into clinical practice. This study was designed to assess the safety, feasibility, and efficacy of TEEM in a series of patients with achalasia. Under institutional review board approval, patients were enrolled on our study, where TEEM was offered as an alternative to laparoscopic or robotic Heller myotomy. The inclusion criteria were patients with achalasia confirmed by esophageal manometry, between age 18 and 50 years, and ASA class 2 or lower. The exclusion criteria were pregnancy, prior esophageal surgery, immunosuppression, coagulopathies, and severe medical comorbidities. The procedures were performed under general anesthesia, with the patient in supine position on positive pressure ventilation. With a GIF-180 (Olympus, Tokyo, Japan) positioned at 10 cm above the GEJ, a mucosotomy was performed at the 2 o'clock position, and a submucosal space was developed caudally creating a controlled submucosal tunnel extending 2 cm distal to the GEJ. Upon completion of this tunnel the gastroesophageal lumen was inspected for mucosal integrity. The scope was then reinserted into the submucosal tunnel and using a triangle-tip knife, myotomy was performed starting at 5 cm above the GEJ and ending at 2 cm below the GEJ. During this process the circular muscle layer of the esophagus was carefully divided with preservation of the longitudinal layer. At the end of the procedure, the mucosal incision was closed longitudinally with endoscopic clips and surgical glue. Five patients underwent TEEM, with no perioperative complication. All patients reported significant improvement of their dysphagia immediately after the procedure. On the first postoperative day, all barium swallows showed disappearance of the classical bird beak taper, rapid emptying of contrast into the stomach, and absence of leaks. All patients were discharged on the second postoperative day on liquid diet. Two patients reported transient heartburn, which were well controlled with medications. The average preoperative GERD-HRQL was 20, which improved to 11.3 at 7 days postoperative and 2 at 30 days postoperative. To date, three patients have already returned for their 6-month follow-up, reporting adequate swallowing and low LES pressures on esophageal manometry (their mean preoperative LES resting pressure was 36.46 mmHg and residual pressure was 43.16 mmHg, whereas the 6-month follow-up mean LES resting pressure was 10.06 mmHg and residual pressure was 0.43 mmHg). TEEM seems to be safe, feasible, and effective for the treatment of patients with achalasia. Long-term data are still necessary for wide-spread utilization of this novel technique. C1 [Meireles, Ozanan R.; Horgan, Santiago; Jacobsen, Garth R.; Katagiri, Toshio; Mathew, Abraham; Sedrak, Michael; Sandler, Bryan J.; Dotai, Takayuki; Majid, Saniea F.; Nijhawan, Sheetal; Talamini, Mark A.] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Meireles, Ozanan R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Mathew, Abraham] Penn State Milton S Hershey Med Ctr, Dept Gastroenterol, Hershey, PA USA. [Savides, Thomas J.] Univ Calif San Diego, Dept Gastroenterol, San Diego, CA 92103 USA. RP Meireles, OR (reprint author), Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. EM omeireles@partners.org NR 15 TC 7 Z9 7 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAY PY 2013 VL 27 IS 5 BP 1803 EP 1809 DI 10.1007/s00464-012-2666-9 PG 7 WC Surgery SC Surgery GA 129PG UT WOS:000317853100049 PM 23525881 ER PT J AU Bair, SM Choueiri, TK Moslehi, J AF Bair, Steven M. Choueiri, Toni K. Moslehi, Javid TI Cardiovascular complications associated with novel angiogenesis inhibitors: Emerging evidence and evolving perspectives SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; ARTERIAL THROMBOEMBOLIC EVENTS; RANDOMIZED CONTROLLED-TRIALS; NITRIC-OXIDE SYNTHASE; METASTATIC COLORECTAL-CANCER; TREATMENT-RELATED MORTALITY; ACTIVATED PROTEIN-KINASE; BLOOD-PRESSURE; FLK-1/KDR ACTIVATION AB Novel cancer therapies targeting tumor angiogenesis have revolutionized treatment options in a variety of tumors. Specifically, VEGF signaling pathway (VSP) inhibitors have been introduced into clinical practice at a rapid pace over the last decade. It is becoming increasingly clear that VSP inhibitors can cause cardiovascular toxicities including hypertension, thrombosis, and heart failure. This review highlights these toxicities and proposes several strategies in their prevention and treatment. However, we recognize the dearth of data in this area and advocate a multi-disciplinary approach involving cardiologists and oncologists, as well as clinical and translational studies, in understanding and treating VSP-inhibitor associated toxicities. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bair, Steven M.; Moslehi, Javid] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Bair, Steven M.; Choueiri, Toni K.; Moslehi, Javid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Moslehi, Javid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. [Moslehi, Javid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Adult Survivorship Clin, Boston, MA 02115 USA. RP Moslehi, J (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Cardiooncol Program, 75 Francis St, Boston, MA 02115 USA. EM jmoslehi@partners.org FU Stanley Sarnoff Fellowship; NIH Career Development Award [K08]; Watkins Discovery Award Program; Cardiovascular Leadership Council Investigator Award (both by Brigham and Women's Hospital) FX We thank Drs. James Michael Kirshenbaum and William George Kaelin, Jr. for critical review of the manuscript. SMB is supported by the Stanley Sarnoff Fellowship. JM is supported by an NIH Career Development Award (K08), Watkins Discovery Award Program, and Cardiovascular Leadership Council Investigator Award (both by Brigham and Women's Hospital). The authors thank Dr. William G. Kaelin, Jr. for his continuous mentorship. NR 65 TC 30 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD MAY PY 2013 VL 23 IS 4 BP 104 EP 113 DI 10.1016/j.tcm.2012.09.008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 130BD UT WOS:000317886800003 PM 23290365 ER PT J AU Palevsky, PM Liu, KD Brophy, PD Chawla, LS Parikh, CR Thakar, CV Tolwani, AJ Waikar, SS Weisbord, SD AF Palevsky, Paul M. Liu, Kathleen D. Brophy, Patrick D. Chawla, Lakhmir S. Parikh, Chirag R. Thakar, Charuhas V. Tolwani, Ashita J. Waikar, Sushrut S. Weisbord, Steven D. TI KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID CONTRAST-INDUCED NEPHROPATHY; ACUTE-RENAL-FAILURE; RANDOMIZED CONTROLLED-TRIAL; CRITICALLY-ILL PATIENTS; PERCUTANEOUS CORONARY INTERVENTION; RADIOCONTRAST-INDUCED NEPHROPATHY; INTRAVENOUS N-ACETYLCYSTEINE; GOAL-DIRECTED THERAPY; ISOTONIC SODIUM-BICARBONATE; PLACEBO-CONTROLLED TRIAL AB In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI. Am J Kidney Dis. 61(5): 649-672. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Palevsky, Paul M.; Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.; Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Brophy, Patrick D.] Univ Iowa, Dept Pediat, Carver Coll Med, Div Nephrol, Iowa City, IA 52242 USA. [Chawla, Lakhmir S.] George Washington Univ, Dept Anesthesiol & Crit Care Med, Washington, DC USA. [Chawla, Lakhmir S.] George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Washington, DC USA. [Parikh, Chirag R.] VA Connecticut Healthcare Syst, Renal Sect, West Haven, CT USA. [Parikh, Chirag R.] Yale Univ, Sch Med, Dept Med, Nephrol Sect, New Haven, CT 06510 USA. [Thakar, Charuhas V.] Cincinnati VA Med Ctr, Renal Sect, Cincinnati, OH USA. [Thakar, Charuhas V.] Univ Cincinnati, Dept Internal Med, Div Nephrol & Hypertens, Cincinnati, OH USA. [Tolwani, Ashita J.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Waikar, Sushrut S.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Rm 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 164 TC 99 Z9 122 U1 1 U2 22 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 MAY PY 2013 VL 61 IS 5 BP 649 EP 672 DI 10.1053/j.ajkd.2013.02.349 PG 24 WC Urology & Nephrology SC Urology & Nephrology GA 121WV UT WOS:000317276600003 PM 23499048 ER PT J AU Koyner, JL Garg, AX Shlipak, MG Patel, UD Sint, K Hong, K Devarajan, P Edelstein, CL Zappitelli, M Thiessen-Philbrook, H Parikh, CR AF Koyner, Jay L. Garg, Amit X. Shlipak, Michael G. Patel, Uptal D. Sint, Kyaw Hong, Kwangik Devarajan, Prasad Edelstein, Charles L. Zappitelli, Michael Thiessen-Philbrook, Heather Parikh, Chirag R. CA Translational Res Investigating TI Urinary Cystatin C and Acute Kidney Injury After Cardiac Surgery SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Acute kidney injury biomarkers; cystatin C; dialysis; perioperative ID GLOMERULAR-FILTRATION-RATE; INTENSIVE-CARE-UNIT; ACUTE-RENAL-FAILURE; PREDICTS MORTALITY; POOR OUTCOMES; BIOMARKERS; DURATION; THERAPY; MARKERS AB Background: Acute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and may increase earlier in AKI than serum creatinine level. Study Design: Prospective cohort study. Settings & Participants: The TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children and adolescents at 8 institutions in 2007-2009. Index Test: Urinary CysC (in milligrams per liter) within the first 12 hours after surgery. Outcome: Serum creatinine-based AKI was defined as AKI Network stage 1 (mild AKI) and doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization (severe AKI). Other Measurements: Analyses were adjusted for characteristics used clinically for AKI risk stratification, including age, sex, race, estimated glomerular filtration rate, diabetes, hypertension, heart failure, nonelective surgery, cardiac catheterization within 72 hours, type of surgery, myocardial infarction, and cardiopulmonary bypass time longer than 120 minutes. Results: Urinary CysC level measured in the early postoperative period (0-6 and 6-12 hours postoperatively) correlated with both mild and severe AKI in adults and children. However, after analyses were adjusted for other factors, the effect was attenuated for both forms of AKI in both cohorts. Limitations: Limited numbers of patients with severe AKI and in-hospital dialysis treatment. Conclusions: Urinary CysC values are not associated significantly with the development of AKI after cardiac surgery in adults and children. Am J Kidney Dis. 61(5): 730-738. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Garg, Amit X.; Thiessen-Philbrook, Heather] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. [Patel, Uptal D.] Duke Univ, Sch Med, Durham, NC USA. [Sint, Kyaw; Hong, Kwangik; Parikh, Chirag R.] Yale Univ, Sch Med, Nephrol Sect, New Haven, CT 06510 USA. [Sint, Kyaw; Hong, Kwangik; Parikh, Chirag R.] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT USA. [Devarajan, Prasad] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Edelstein, Charles L.] Univ Colorado, Div Renal Dis, Denver, CO 80202 USA. [Zappitelli, Michael] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat,Div Nephrol, Montreal, PQ H3H 1P3, Canada. RP Parikh, CR (reprint author), Yale Univ, Program Appl Translat Res, 60 Temple St,Ste 6C, New Haven, CT 06510 USA. EM chirag.parikh@yale.edu FU American Heart Association Clinical Development Award; National Heart, Lung and Blood Institute [R01HL-085757]; National Center for Research Resources [UL1 RR024139]; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK081616]; National Institutes of Health [K24DK090203, U01DK082185] FX The research reported in this article was supported by the American Heart Association Clinical Development Award and National Heart, Lung and Blood Institute grant R01HL-085757 (to Dr Parikh). The study was also supported by Clinical and Translational Science Award grant UL1 RR024139 from the National Center for Research Resources. Dr Koyner was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK081616. Dr Parikh was also supported by National Institutes of Health grants K24DK090203 and U01DK082185. Urinary CysC assays were donated by Sekisui Diagnostics LLC. Sekisui Diagnostics LLC did not participate in the protocol development, analysis, or interpretation of the results. NR 32 TC 14 Z9 18 U1 0 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2013 VL 61 IS 5 BP 730 EP 738 DI 10.1053/j.ajkd.2012.12.006 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 121WV UT WOS:000317276600014 PM 23332602 ER PT J AU Blauwet, C Sudhakar, S Doherty, AL Garshick, E Zafonte, R Morse, LR AF Blauwet, Cheri Sudhakar, Supreetha Doherty, Ashley L. Garshick, Eric Zafonte, Ross Morse, Leslie R. TI Participation in Organized Sports Is Positively Associated with Employment in Adults with Spinal Cord Injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Spinal Cord Injury; Employment; Sports; Exercise ID QUALITY-OF-LIFE; WORK; EARNINGS; PEOPLE; TAIWAN; RETURN; RACE; INDIVIDUALS; OUTCOMES; TIME AB Blauwet C, Sudhakar S, Doherty AL, Garshick E, Zafonte R, Morse LR: Participation in organized sports is positively associated with employment in adults with spinal cord injury. Am J Phys Med Rehabil 2013;92:393-401. Objective: The aim of this study was to determine the association between participation in organized sports programs and employment in adults with chronic spinal cord injury. Design: This is a cross-sectional study of 149 adults with chronic spinal cord injury. Motor level and completeness of injury were confirmed by physical examination. Information related to demographics, employment, level of education, body mass index, duration of injury, participation in individually planned exercise, and participation in organized sports was obtained using a standardized questionnaire. Multivariable logistic regression analyses were used to assess factors associated with employment. Results: In univariate analyses, employment was associated with younger age (P = 0.001) and a higher level of education (P = 0.01), whereas obesity decreased the likelihood of employment (P = 0.04). Participation in organized sports approached significance (P = 0.06). In the multivariable analysis and after adjusting for age, education, and body mass index, participation in organized sports was significantly associated with employment (odds ratio, 2.4; P = 0.04). Sex, duration of injury, wheelchair use, and participation in individually planned exercise were not significantly associated with employment (P = 0.16-0.94). Conclusions: In the adults with chronic spinal cord injury, participation in organized sports was positively associated with employment. Further studies are necessary to determine the causative nature of this association and how various factors related to sports participation may contribute. C1 [Blauwet, Cheri; Zafonte, Ross; Morse, Leslie R.] Harvard Univ, Dept Phys Med & Rehabil, Sch Med, Boston, MA 02114 USA. [Blauwet, Cheri; Sudhakar, Supreetha; Doherty, Ashley L.; Zafonte, Ross; Morse, Leslie R.] Spaulding Rehabil Hosp, Spaulding Harvard Model Syst, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, Boston, MA USA. [Garshick, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02114 USA. RP Morse, LR (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Sch Med, SH SCI Model Syst,Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. RI Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [1R01AR059270]; Department of Veterans Affairs Office of Research and Development; Rehabilitation Research and Development Merit Review Grant [B6618R]; Department of Education, National Institute on Disability and Rehabilitation Research [H133N110010] FX Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 1R01AR059270; the Department of Veterans Affairs Office of Research and Development; Rehabilitation Research and Development Merit Review Grant B6618R; and the Department of Education, National Institute on Disability and Rehabilitation Research grant H133N110010. NR 31 TC 7 Z9 7 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2013 VL 92 IS 5 BP 393 EP 401 DI 10.1097/PHM.0b013e3182876a5f PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 130LV UT WOS:000317919600003 PM 23478458 ER PT J AU Zamarioli, A Battaglino, RA Morse, LR Sudhakar, S Maranho, DAC Okubo, R Volpon, JB Shimano, AC AF Zamarioli, Ariane Battaglino, Ricardo A. Morse, Leslie R. Sudhakar, Supreetha Maranho, Daniel A. C. Okubo, Rodrigo Volpon, Jose B. Shimano, Antonio C. TI Standing Frame and Electrical Stimulation Therapies Partially Preserve Bone Strength in a Rodent Model of Acute Spinal Cord Injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Bone Fracture; Osteoporosis; Spinal Cord Injury; Rehabilitation Medicine ID MINERAL DENSITY; CORTICAL BONE; BIOMECHANICAL PROPERTIES; PARAPLEGIC PATIENTS; MUSCLE ATROPHY; INDIVIDUALS; MASS; RAT; OSTEOPOROSIS; METABOLISM AB Zamarioli A, Battaglino RA, Morse LR, Sudhakar S, Maranho DAC, Okubo R, Volpon JB, Shimano AC: Standing frame and electrical stimulation therapies partially preserve bone strength in a rodent model of acute spinal cord injury. Am J Phys Med Rehabil 2013;92:402-410. Objective: The aim of this study was to compare the effect of standing frame and electrical stimulation on bone quality in a rodent transection model of spinal cord injury (SCI). Design: Seven-week-old male Wistar rats were divided into four groups: sham, n = 10; SCI, n = 7; SCI + standing frame, n = 7; and SCI + electrical stimulation, n = 7. Complete SCI was generated by surgical transection of the cord at the T10 level. Therapies were initiated 3 days after the surgery, 3 days/wk, 20 mins/day, for 30 days. Animals were killed on day 33 postinjury. Results: No treatment preserved bone mineral density at any skeletal site tested (P = 0.08-0.99). Standing frame therapy preserved maximal load at the lumbar vertebral body (14% vs. 37% reduction, P = 0.01) and prevented SCI-induced loss of stiffness at both the femur (8% vs. 37% reduction, P = 0.03) and the tibia (35% vs. 56% reduction, P < 0.0001). Electrical stimulation therapy reduced SCI-induced loss of stiffness at the tibia only (40% vs. 56% reduction, P = 0.003). Conclusions: Standing frame and electrical stimulation may have potential as future therapeutic modalities to treat or prevent bone loss after SCI. C1 [Zamarioli, Ariane; Maranho, Daniel A. C.; Okubo, Rodrigo; Volpon, Jose B.; Shimano, Antonio C.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biomech Med & Rehabil, Sao Paulo, Brazil. [Zamarioli, Ariane; Battaglino, Ricardo A.; Morse, Leslie R.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA USA. [Battaglino, Ricardo A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Morse, Leslie R.; Sudhakar, Supreetha] Spaulding Rehabil Hosp, Boston, MA USA. RP Zamarioli, A (reprint author), Univ Sao Paulo FMRP USP, Fac Med Ribeirao Preto, Lab Bioengn, Dept Biomech Med & Rehabil, Casa 1,3900 Av Bandeirantes, BR-14049900 Ribeirao Preto, SP, Brazil. RI Zamarioli, Ariane/K-7001-2012; Volpon, Jose /D-3041-2012; Maranho, Daniel Augusto/C-1337-2013; Morse, Leslie/C-9442-2015; battaglino, ricardo/D-2892-2015; Shimano, Antonio/E-1455-2014 OI Zamarioli, Ariane/0000-0002-7939-0528; Shimano, Antonio Carlos/0000-0002-3119-2362; Volpon, Jose /0000-0002-2120-0138; Maranho, Daniel Augusto/0000-0002-3893-0292; Morse, Leslie/0000-0002-7426-6341; FU Foundation for Research Support of the State of Sao Paulo (FAPESP), Brazil FX Supported by the Foundation for Research Support of the State of Sao Paulo (FAPESP), Brazil. NR 54 TC 7 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2013 VL 92 IS 5 BP 402 EP 410 DI 10.1097/PHM.0b013e318287697c PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 130LV UT WOS:000317919600004 PM 23478455 ER PT J AU Hutter, MM AF Hutter, Matthew M. TI Laparoscopic Sleeve Gastrectomy Is Safe and Effective and Should Be a Covered Benefit SO ANNALS OF SURGERY LA English DT Editorial Material ID BARIATRIC SURGERY C1 Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, 15 Parkman St,Wang ACC 335, Boston, MA 02114 USA. EM mhutter@partners.org NR 6 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2013 VL 257 IS 5 BP 798 EP 799 DI 10.1097/SLA.0b013e318290d5e5 PG 2 WC Surgery SC Surgery GA 126CQ UT WOS:000317589500002 PM 23574988 ER PT J AU Tilt, AC Werner, PD Brown, DF Alam, HB Warshaw, AL Parry, BA Jazbar, B Booker, A Stangenberg, L Fricchione, GL Benson, H Lillemoe, KD Conrad, C AF Tilt, Alexandra C. Werner, Paul D. Brown, David F. Alam, Hassan B. Warshaw, Andrew L. Parry, Blair A. Jazbar, Brigita Booker, Abigail Stangenberg, Lars Fricchione, Gregory L. Benson, Herbert Lillemoe, Keith D. Conrad, Claudius TI Low Degree of Formal Education and Musical Experience Predict Degree of Music-Induced Stress Reduction in Relatives and Friends of Patients A Single-Center, Randomized Controlled Trial SO ANNALS OF SURGERY LA English DT Article DE education; gender; music; music experience; predictabaility of anxiolysis; relatives of patients ID PATIENTS ANXIETY; PREOPERATIVE ANXIETY; INTERVENTION; THERAPY AB Objective: To determine the factors that may predict music-induced relaxation in friends and family of patients in the emergency department. Background: It remains unclear to date which demographic and experiential factors predict the effectiveness of music-induced relaxation. Furthermore, in-hospital stressors for friends and family of patients rather than patients themselves are underresearched and deserve in-depth investigation to improve this group's experience in health care environments. Methods: A total of 169 relatives and friends of patients in the emergency department-waiting area completed a series of questionnaires, including the Spielberger State-Trait Anxiety Inventory (STAI), the Music Experience Questionnaire (MEQ), and a demographic survey. They were then randomly assigned to either Case Group (1 hour in the waiting area with classical music in the background) or Control Group (1 hour with no music) before completing a second, identical copy of the STAI to measure change from baseline. Data were analyzed for associations between music intervention, change in STAI scores, MEQ scores, and demographic characteristics. Results: Participants who underwent the music intervention experienced a 9.8% decrease in overall mean State Anxiety, whereas those in the Control Group experienced no change over time (P = 0.001). Higher education significantly inversely correlated with the effectiveness of music intervention: participants with no formal education beyond high school showed a greater overall mean decrease in State Anxiety than those with a college education or beyond in response to classical music (P = 0.006). Furthermore, MEQ scores indicated that the Social Uplift scale (a measure of one's tendency to be uplifted in a group-oriented manner by music) was highly predictive of the effectiveness of music intervention. Conclusions: Music is an effective and inexpensive means of reducing anxiety in friends and family of patients, who are underresearched in medicine. Moreover, low educational attainment and tendency to respond positively to music in a group setting can predict the effectiveness of music-induced relaxation. C1 [Tilt, Alexandra C.; Alam, Hassan B.; Warshaw, Andrew L.; Jazbar, Brigita; Booker, Abigail; Stangenberg, Lars; Lillemoe, Keith D.; Conrad, Claudius] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Brown, David F.; Parry, Blair A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Fricchione, Gregory L.; Benson, Herbert] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Werner, Paul D.] Alliant Int Univ, Calif Sch Profess Psychol, PhD Program Clin Psychol, San Francisco, CA USA. RP Conrad, C (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02215 USA. EM cconrad@partners.org NR 25 TC 2 Z9 2 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2013 VL 257 IS 5 BP 834 EP 838 DI 10.1097/SLA.0b013e31828ee1da PG 5 WC Surgery SC Surgery GA 126CQ UT WOS:000317589500008 PM 23574990 ER PT J AU Gutu, AD Sgambati, N Strasbourger, P Brannon, MK Jacobs, MA Haugen, E Kaul, RK Johansen, HK Hoiby, N Moskowitz, SM AF Gutu, Alina D. Sgambati, Nicole Strasbourger, Pnina Brannon, Mark K. Jacobs, Michael A. Haugen, Eric Kaul, Rajinder K. Johansen, Helle Krogh Hoiby, Niels Moskowitz, Samuel M. TI Polymyxin Resistance of Pseudomonas aeruginosa phoQ Mutants Is Dependent on Additional Two-Component Regulatory Systems SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CYSTIC-FIBROSIS PATIENTS; CATIONIC ANTIMICROBIAL PEPTIDES; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; LIPID-A; PMRA-PMRB; OUTER-MEMBRANE; ACINETOBACTER-BAUMANNII; PHOSPHATASE-ACTIVITIES; ADAPTIVE RESISTANCE AB Pseudomonas aeruginosa can develop resistance to polymyxin as a consequence of mutations in the PhoPQ regulatory system, mediated by covalent lipid A modification. Transposon mutagenesis of a polymyxin-resistant phoQ mutant defined 41 novel loci required for resistance, including two regulatory systems, ColRS and CprRS. Deletion of the colRS genes, individually or in tandem, abrogated the polymyxin resistance of a Delta phoQ mutant, as did individual or tandem deletion of cprRS. Individual deletion of colR or colS in a Delta phoQ mutant also suppressed 4-amino-L-arabinose addition to lipid A, consistent with the known role of this modification in polymyxin resistance. Surprisingly, tandem deletion of colRS or cprRS in the Delta phoQ mutant or individual deletion of cprR or cprS failed to suppress 4-amino-L-arabinose addition to lipid A, indicating that this modification alone is not sufficient for PhoPQ-mediated polymyxin resistance in P. aeruginosa. Episomal expression of colRS or cprRS in tandem or of cprR individually complemented the Pm resistance phenotype in the Delta phoQ mutant, while episomal expression of colR, colS, or cprS individually did not. Highly polymyxin-resistant phoQ mutants of P. aeruginosa isolated from polymyxin-treated cystic fibrosis patients harbored mutant alleles of colRS and cprS; when expressed in a Delta phoQ background, these mutant alleles enhanced polymyxin resistance. These results define ColRS and CprRS as two-component systems regulating polymyxin resistance in P. aeruginosa, indicate that addition of 4-amino-L-arabinose to lipid A is not the only PhoPQ-regulated biochemical mechanism required for resistance, and demonstrate that colRS and cprS mutations can contribute to high-level clinical resistance. C1 [Gutu, Alina D.; Sgambati, Nicole; Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Strasbourger, Pnina; Brannon, Mark K.; Moskowitz, Samuel M.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Jacobs, Michael A.; Haugen, Eric; Kaul, Rajinder K.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Johansen, Helle Krogh; Hoiby, Niels] Copenhagen CF Ctr, Dept Clin Microbiol, Copenhagen, Denmark. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Moskowitz, SM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM smoskowitz@partners.org OI Haugen, Eric/0000-0001-7444-8981 FU National Heart Lung and Blood Institute [K08HL067903]; National Institute of Allergy and Infectious Diseases [R01AI067653]; CF Foundation [MOSKOW01A1]; Novo Nordisk Foundation FX This work was supported by Public Health Service grants K08HL067903 to S.M.M. from the National Heart Lung and Blood Institute and R01AI067653 to S.M.M. from the National Institute of Allergy and Infectious Diseases. This work was also supported by grant MOSKOW01A1 to S.M.M. from the CF Foundation. H.K.J. was supported by a clinical research stipend from the Novo Nordisk Foundation. NR 73 TC 23 Z9 23 U1 1 U2 21 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2013 VL 57 IS 5 BP 2204 EP 2215 DI 10.1128/AAC.02353-12 PG 12 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 124ME UT WOS:000317467600028 PM 23459479 ER PT J AU van Gils, JM Ramkhelawon, B Fernandes, L Stewart, MC Guo, L Seibert, T Menezes, GB Cara, DC Chow, C Kinane, TB Fisher, EA Balcells, M Alvarez-Leite, J Lacy-Hulbert, A Moore, KJ AF van Gils, Janine M. Ramkhelawon, Bhama Fernandes, Luciana Stewart, Merran C. Guo, Liang Seibert, Tara Menezes, Gustavo B. Cara, Denise C. Chow, Camille Kinane, T. Bernard Fisher, Edward A. Balcells, Mercedes Alvarez-Leite, Jacqueline Lacy-Hulbert, Adam Moore, Kathryn J. TI Endothelial Expression of Guidance Cues in Vessel Wall Homeostasis Dysregulation Under Proatherosclerotic Conditions SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; axonal guidance; endothelial-leukocyte interaction; migration ID INHIBITS LEUKOCYTE MIGRATION; EPHRINB2 EXPRESSION; CELL-INTERACTIONS; IN-VIVO; ATHEROSCLEROSIS; ATHEROGENESIS; INFLAMMATION; RETENTION; RECEPTORS AB Objective-Emerging evidence suggests that neuronal guidance cues, typically expressed during development, are involved in both physiological and pathological immune responses. We hypothesized that endothelial expression of such guidance cues may regulate leukocyte trafficking into the vascular wall during atherogenesis. Approach and Results-We demonstrate that members of the netrin, semaphorin, and ephrin family of guidance molecules are differentially regulated under conditions that promote or protect from atherosclerosis. Netrin-1 and semaphorin3A are expressed by coronary artery endothelial cells and potently inhibit chemokine-directed migration of human monocytes. Endothelial expression of these negative guidance cues is downregulated by proatherogenic factors, including oscillatory shear stress and proinflammatory cytokines associated with monocyte entry into the vessel wall. Furthermore, we show using intravital microscopy that inhibition of netrin-1 or semaphorin3A using blocking peptides increases leukocyte adhesion to the endothelium. Unlike netrin-1 and semaphorin3A, the guidance cue ephrinB2 is upregulated under proatherosclerotic flow conditions and functions as a chemoattractant, increasing leukocyte migration in the absence of additional chemokines. Conclusions-The concurrent regulation of negative and positive guidance cues may facilitate leukocyte infiltration of the endothelium through a balance between chemoattraction and chemorepulsion. These data indicate a previously unappreciated role for axonal guidance cues in maintaining the endothelial barrier and regulating leukocyte trafficking during atherogenesis. (Arterioscler Thromb Vasc Biol. 2013; 33: 911-919.) C1 [van Gils, Janine M.; Ramkhelawon, Bhama; Stewart, Merran C.; Guo, Liang; Fisher, Edward A.; Moore, Kathryn J.] NYU, Sch Med, Marc & Ruti Bell Vasc Biol & Dis Program, Leon H Charney Div Cardiol,Dept Med, New York, NY 10016 USA. [Fernandes, Luciana; Menezes, Gustavo B.; Cara, Denise C.; Alvarez-Leite, Jacqueline] Univ Fed Minas Gerais, Dept Biochem & Immunol, Belo Horizonte, MG, Brazil. [Seibert, Tara] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Chow, Camille; Kinane, T. Bernard; Lacy-Hulbert, Adam] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol, Boston, MA USA. [Balcells, Mercedes] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Balcells, Mercedes] Ramon Llull Univ, Inst Quim Sarria, IQS Sch Engn, Barcelona, Spain. RP Moore, KJ (reprint author), NYU, Sch Med, 522 1st Ave,Smilow 705, New York, NY 10016 USA. EM Kathryn.moore@nyumc.org OI Balcells, Mercedes/0000-0002-2532-0516; Lacy-Hulbert, Adam/0000-0003-2162-0156; Moore, kathryn/0000-0003-2505-2547; Guo, Liang/0000-0003-1633-1544; Fisher, Edward/0000-0001-9802-143X FU American Heart Association [0655840T, 09POST2080250]; Fondation de la recherche Medicale; National Institutes of Health [RC1HL100815, R01 HL084312, R01/GM049039]; Canadian Institute of Health Research (CGS-MSFSS); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [01558/2007-6]; Ministerio de Innovacion Plan Nacional [BFU2009-09804]; Fundacio Empreses IQS; POSIMAT FX Support for this work came from the American Heart Association (Grant-in-aid 0655840T to K.J.M.; 09POST2080250 to J.M.V.G.), Fondation de la recherche Medicale to B.R., National Institutes of Health (RC1HL100815 to K.J.M.; R01 HL084312 to E. A. F.; R01/GM049039 to M. B.), Canadian Institute of Health Research (CGS-MSFSS to T. S.), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (01558/2007-6 to L. R. F. and J.I.A.-L.), Ministerio de Innovacion Plan Nacional BFU2009-09804 (M. B.), Fundacio Empreses IQS (M. B.), and POSIMAT (M.B.). NR 29 TC 20 Z9 21 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2013 VL 33 IS 5 BP 911 EP U108 DI 10.1161/ATVBAHA.112.301155 PG 17 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 124PB UT WOS:000317476000011 PM 23430612 ER PT J AU Li, W Li, QL Qin, LF Ali, R Qyang, YB Tassabehji, M Pober, BR Sessa, WC Giordano, FJ Tellides, G AF Li, Wei Li, Qingle Qin, Lingfeng Ali, Rahmat Qyang, Yibing Tassabehji, May Pober, Barbara R. Sessa, William C. Giordano, Frank J. Tellides, George TI Rapamycin Inhibits Smooth Muscle Cell Proliferation and Obstructive Arteriopathy Attributable to Elastin Deficiency SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE aorta; elastin; mTOR; smooth muscle cell; Williams syndrome ID WILLIAMS-BEUREN-SYNDROME; SUPRAVALVULAR AORTIC-STENOSIS; INTERFERON-GAMMA; SIROLIMUS; MICE; TRANSPLANT; DISEASE; GROWTH; MOUSE; SUPPRESSION AB Objective-Patients with elastin deficiency attributable to gene mutation (supravalvular aortic stenosis) or chromosomal microdeletion (Williams syndrome) are characterized by obstructive arteriopathy resulting from excessive smooth muscle cell (SMC) proliferation, mural expansion, and inadequate vessel size. We investigated whether rapamycin, an inhibitor of the cell growth regulator mammalian target of rapamycin (mTOR) and effective against other SMC proliferative disorders, is of therapeutic benefit in experimental models of elastin deficiency. Approach and Results-As previously reported, Eln(-/-) mice demonstrated SMC hyperplasia and severe stenosis of the aorta, whereas Eln(+/-) mice exhibited a smaller diameter aorta with more numerous but thinner elastic lamellae. Increased mTOR signaling was detected in elastin-deficient aortas of newborn pups that was inhibited by maternal administration of rapamycin. mTOR inhibition reduced SMC proliferation and aortic obstruction in Eln(-/-) pups and prevented medial hyperlamellation in Eln(+/-) weanlings without compromising aortic size. However, rapamycin did not prolong the survival of Eln(-/-) pups, and it retarded the somatic growth of juvenile Eln(+/-) and Eln(+/+) mice. In cell cultures, rapamycin inhibited prolonged mTOR activation and enhanced proliferation of SMC derived from patients with supravalvular aortic stenosis and with Williams syndrome. Conclusions-mTOR inhibition may represent a pharmacological strategy to treat diffuse arteriopathy resulting from elastin deficiency. (Arterioscler Thromb Vasc Biol. 2013; 33: 1028-1035.) C1 [Li, Wei; Li, Qingle; Qin, Lingfeng; Ali, Rahmat; Tellides, George] Yale Univ, Sch Med, Dept Surg, Interdept Program Vasc Biol & Therapeut, New Haven, CT 06510 USA. [Qyang, Yibing; Giordano, Frank J.] Yale Univ, Sch Med, Dept Med, Interdept Program Vasc Biol & Therapeut, New Haven, CT 06510 USA. [Sessa, William C.] Yale Univ, Sch Med, Dept Pharmacol, Interdept Program Vasc Biol & Therapeut, New Haven, CT 06510 USA. [Tassabehji, May] Univ Manchester, Dept Med Genet, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Pober, Barbara R.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Tellides, George] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. RP Tellides, G (reprint author), 10 Amistad St 337B, New Haven, CT 06520 USA. EM george.tellides@yale.edu FU Kiev Foundation; Williams Syndrome Association; Wellcome Trust FX This work was supported by the Kiev Foundation and the Williams Syndrome Association (W.C. Sessa, F.J. Giordano, G. Tellides) and The Wellcome Trust (M. Tassabehji). NR 29 TC 9 Z9 10 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2013 VL 33 IS 5 BP 1028 EP U400 DI 10.1161/ATVBAHA.112.300407 PG 17 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 124PB UT WOS:000317476000025 PM 23493289 ER PT J AU Weng, TY Chiu, WT Liu, HS Cheng, HC Shen, MR Mount, DB Chou, CY AF Weng, Tzu-Yu Chiu, Wen-Tai Liu, Hsiao-Sheng Cheng, Hung-Chi Shen, Meng-Ru Mount, David B. Chou, Cheng-Yang TI Glycosylation regulates the function and membrane localization of KCC4 SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE KCC4; N-linked glycosylation; Glycan complexity; Membrane expression; Tumor formation ID CELL-SURFACE EXPRESSION; OVARIAN-CANCER CELLS; KCL COTRANSPORT; N-GLYCOSYLATION; ENDOPLASMIC-RETICULUM; CL-COTRANSPORTER; CERVICAL-CANCER; INVASION; GLYCANS; PROLIFERATION AB Glycosylation plays a role in regulating many biological activities, including protein folding and cell surface expression of biomolecules. However, the importance of glycosylation for KCC4 function has not previously been demonstrated. Site-directed mutagenesis was performed on the four putative extracellular N-linked glycosylation sites of KCC4 to determine the role of these sites in KCC4 half-life, cell surface expression, and transporter activity, as well as in KCC4-dependent tumor formation. We showed that triple (N312/331/344/Q) and quadruple (N312/331/344/360/Q) mutations of N-linked glycosylation sites disrupt the N-linked glycosylation of KCC4, resulting in the accumulation of KCC4, predominantly in the endoplasmic reticulum (ER) and not at the cell surface. Further investigation indicated that mutations of the central two (N331/344/Q) N-linked glycosylation sites inhibit the membrane trafficking of KCC4. Our data suggest that the glycan moieties at the N331 and N344 sites were Endo H-resistant, complex-form structures, and that the N312 and N360 sites were Endo H-sensitive, high mannose-containing structures. Under hypotonic stress conditions, the ability to adapt to changes in intracellular chloride ion concentrations and RVD (regulatory volume decrease) activities were less efficient in cells containing the deglycosylated form of KCC4 that were not expressed at the cell surface. Deglycosylated forms of KCC4 also demonstrated decreased tumor formation and lung colonization in mouse xenografts. The difference in glycan complexity may account for the differential impact of each branch on the biological effects of KCC4. We propose that glycosylation is essential for the surface expression, stabilization, and bioactivity of KCC4. (c) 2013 Elsevier B.V. All rights reserved. C1 [Weng, Tzu-Yu] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 704, Taiwan. [Chiu, Wen-Tai] Natl Cheng Kung Univ, Coll Engn, Dept Biomed Engn, Tainan 704, Taiwan. [Liu, Hsiao-Sheng] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 704, Taiwan. [Cheng, Hung-Chi] Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan 704, Taiwan. [Shen, Meng-Ru; Chou, Cheng-Yang] Natl Cheng Kung Univ, Coll Med, Dept Obstet & Gynecol, Tainan 70403, Taiwan. [Mount, David B.] VA Boston Healthcare Syst, Brigham & Womens Hosp, Div Renal, Boston, MA USA. RP Chou, CY (reprint author), Natl Cheng Kung Univ & Hosp, Coll Med, Dept Obstet & Gynecol, Tainan 70403, Taiwan. EM chougyn@mail.ncku.edu.tw FU Center of Excellence for Cancer Research in Taiwan [DOH101-TD-C-111-003]; Department of Health, Executive Yuan, Taiwan FX This research was supported by the established Center of Excellence for Cancer Research in Taiwan (DOH101-TD-C-111-003), and the Department of Health, Executive Yuan, Taiwan. NR 30 TC 9 Z9 10 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAY PY 2013 VL 1833 IS 5 BP 1133 EP 1146 DI 10.1016/j.bbamcr.2013.01.018 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 123FT UT WOS:000317374500018 PM 23376777 ER PT J AU McLaughlin, NCR Didie, ER Machado, AG Haber, SN Eskandar, EN Greenberg, BD AF McLaughlin, Nicole C. R. Didie, Elizabeth R. Machado, Andre G. Haber, Suzanne N. Eskandar, Emad N. Greenberg, Benjamin D. TI Improvements in Anorexia Symptoms After Deep Brain Stimulation for Intractable Obsessive-Compulsive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID EATING-DISORDERS; NERVOSA; INDIVIDUALS; DEPRESSION; ACTIVATION; LEUKOTOMY; CHOCOLATE C1 [McLaughlin, Nicole C. R.; Greenberg, Benjamin D.] Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Didie, Elizabeth R.] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Machado, Andre G.] Cleveland Clin, Neurol Inst, Ctr Neurol Restorat, Cleveland, OH 44106 USA. [Haber, Suzanne N.] Univ Rochester, Sch Med, Dept Physiol & Pharmacol, Rochester, NY USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP McLaughlin, NCR (reprint author), Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. EM nicole_mclaughlin@brown.edu RI Machado, Andre/B-7572-2014 OI Machado, Andre/0000-0002-8132-5610 FU NIMH NIH HHS [MH086400, MH73111, P50 MH086400] NR 23 TC 18 Z9 19 U1 0 U2 15 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 MAY 1 PY 2013 VL 73 IS 9 BP E29 EP E31 DI 10.1016/j.biopsych.2012.09.015 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 126AO UT WOS:000317583700004 PM 23128051 ER PT J AU Kuter, DJ Bussel, JB Newland, A Baker, RI Lyons, RM Wasser, J Viallard, JF Macik, G Rummel, M Nie, K Jun, S AF Kuter, David J. Bussel, James B. Newland, Adrian Baker, Ross I. Lyons, Roger M. Wasser, Jeffrey Viallard, Jean-Francois Macik, Gail Rummel, Mathias Nie, Kun Jun, Susie TI Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thrombopoiesis; thrombopoietic agents; TPO receptor agonists; platelets; autoimmunity ID PURPURA ITP; CONTROLLED-TRIAL; DOUBLE-BLIND; IN-VITRO; ELTROMBOPAG; AUTOANTIBODIES; THROMBOPOIETIN; MANAGEMENT; STANDARD; AMG-531 AB Romiplostim was effective, safe, and well-tolerated over 612months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP). This report describes up to 5years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin/fibrosis), platelet response (platelet count >50x109 per litre), and the proportion of patients requiring rescue treatments. Treatmentrelated serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6 center dot 5% of patients and were not associated with platelet count. Median platelet counts of 50200x109 per litre were maintained with stable doses of romiplostim (mean 58g/kg; generally self-administered at home) throughout the study. A platelet response was achieved at least once by 95% of patients, with a platelet response maintained by all patients on a median 92% of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and well-tolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5years of continuous treatment. C1 [Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bussel, James B.] Cornell Univ, Div Hematol, Weill Med Coll, Dept Pediat, New York, NY 10021 USA. [Bussel, James B.] Cornell Univ, Div Hematol, Weill Med Coll, Dept Med, New York, NY 10021 USA. [Newland, Adrian] Royal London Hosp, Dept Haematol, London E1 1BB, England. [Baker, Ross I.] Murdoch Univ, Royal Perth Hosp, Ctr Thrombosis & Haemophilia, Perth, WA, Australia. [Lyons, Roger M.] Canc Care Ctr South Texas US Oncol, San Antonio, TX USA. [Wasser, Jeffrey] Univ Connecticut, Sch Med, Dept Med, Div Hematol Oncol, Farmington, CT USA. [Viallard, Jean-Francois] Univ Bordeaux 2, Hop Haut Leveque, CHU Bordeaux, Pessac, France. [Macik, Gail] Univ Virginia, Charlottesville, VA USA. [Rummel, Mathias] Klinikum Justus Liebig Univ, Giessen, Germany. [Nie, Kun; Jun, Susie] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Yawkey 7858,55 Fruit St, Boston, MA 02114 USA. EM kuter.david@MGH.harvard.edu FU Amgen Inc.; GlaxoSmithKline; Pfizer; Shionogi; ONO; Eisai Inc.; Cangene; Genzyme; IgG of America; Immunomedics; Ligand; Sysmex; Eisai; Octapharma; Roche; Mundipharma FX DK has consulted for and received research funding from Amgen Inc., GlaxoSmithKline, Pfizer, Shionogi, ONO and Eisai Inc. JB has received research funding from Amgen Inc., Cangene, GlaxoSmithKline, Genzyme, IgG of America, Immunomedics, Ligand, Eisai Inc., Shionogi and Sysmex; his family owns stock in Amgen Inc. and GlaxoSmithKline; he has participated in advisory boards for Amgen Inc., GlaxoSmithKline, Ligand, Shionogi, and Eisai Inc., and has consulted for Portola. AN has consulted for and received honoraria from Amgen Inc. and GlaxoSmithKline and has received research funding from Amgen Inc., Eisai, GlaxoSmithKline, and Octapharma. RL has consulted for, received research funding from, and participated in an advisory board for Amgen Inc. JW has consulted for Amgen Inc. and participated in an Amgen advisory board. JFV has participated in advisory boards for and spoken at symposia organized by Amgen Inc. and GlaxoSmithKline. MR has consulted for and received honoraria from Amgen Inc., GlaxoSmithKline, Roche, and Mundipharma, and research funding from Roche and Mundipharma. KN is and SJ was an employee of and stockholder in Amgen Inc. NR 32 TC 66 Z9 70 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2013 VL 161 IS 3 BP 411 EP 423 DI 10.1111/bjh.12260 PG 13 WC Hematology SC Hematology GA 126GV UT WOS:000317602300015 PM 23432528 ER PT J AU Robertson, SM Amspoker, AB Cully, JA Ross, EL Naik, AD AF Robertson, S. M. Amspoker, A. B. Cully, J. A. Ross, E. L. Naik, A. D. TI Affective symptoms and change in diabetes self-efficacy and glycaemic control SO DIABETIC MEDICINE LA English DT Article ID DEPRESSION; STRESS; DISTRESS; ADULTS; TRIAL; CARE AB Aims To examine the role of baseline depression, anxiety and stress symptoms on post-intervention diabetes self-efficacy and glycaemic control (HbA1c). Methods The current study analysed data from patients (n=85) with treated but uncontrolled Type2 diabetes who participated in a comparative effectiveness study of two diabetes self-management interventions. Hierarchical linear regression was used to examine the relationships between baseline affective symptoms and post-intervention diabetes self-efficacy and the moderating effects of baseline affective symptoms on the relationship between changes in diabetes self-efficacy and post-intervention HbA1c. Results Baseline depression was inversely associated with post-intervention diabetes self-efficacy (P=0.0001) after adjusting for baseline characteristics including diabetes self-efficacy. In contrast, normalmild levels of stress were associated with higher post-intervention diabetes self-efficacy (P=0.04). Anxiety and stress symptoms significantly and independently moderated the relationship between changes in diabetes self-efficacy and post-intervention HbA1c (P=0.02 and P=0.03, respectively). Further evaluation of these interactions demonstrated that changes in diabetes self-efficacy were associated with lower post-intervention HbA1c, but only among those with higher baseline affective symptoms. Conclusions We found a moderating effect across affective symptoms on the relationship between diabetes self-efficacy changes and post-intervention HbA1c in the context of a self-management intervention. Results suggest that patients with poorly controlled diabetes who have higher levels of depression, anxiety and stress symptoms may derive greater benefits from self-management interventions known to improve diabetes self-efficacy. C1 [Robertson, S. M.; Amspoker, A. B.; Cully, J. A.; Ross, E. L.; Naik, A. D.] Univ Houston, Michael E DeBakey Vet Affairs Med Ctr, Houston Hlth Serv Res &Development Ctr Excellence, Houston, TX 77004 USA. [Robertson, S. M.; Amspoker, A. B.; Naik, A. D.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Amspoker, A. B.; Cully, J. A.; Naik, A. D.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Cully, J. A.; Naik, A. D.] Univ Houston, VA South Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Ross, E. L.] Univ Houston, Dept Psychol, Houston, TX USA. RP Robertson, SM (reprint author), Univ Houston, Michael E DeBakey Vet Affairs Med Ctr, Houston Hlth Serv Res &Development Ctr Excellence, Houston, TX 77004 USA. EM smr1@bcm.tmc.edu FU Agency for Healthcare Research and Quality; Centers for Research and Education on Therapeutics [U18HS016093]; Doris Duke Charitable Foundation; Veterans Affairs Office of Academic Affiliations; National Institute of Aging [5K23AG027144] FX This manuscript is supported with resources and the use of facilities at the Houston Veterans Affairs Health Services Research and Development Center of Excellence (HEP90-020) at the Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX. The parent study from which the data for the current analysis were derived was funded by the Agency for Healthcare Research and Quality, Centers for Research and Education on Therapeutics (U18HS016093) and a Doris Duke Charitable Foundation Clinical Scientist Development Award (Naik). SMR is a Veterans Affairs Health Services Research post-doc fellow supported by Veterans Affairs Office of Academic Affiliations. ADN received support from a National Institute of Aging Career Development Award (5K23AG027144). NR 27 TC 7 Z9 7 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD MAY PY 2013 VL 30 IS 5 BP E189 EP E196 DI 10.1111/dme.12146 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129SQ UT WOS:000317863000006 PM 23350920 ER PT J AU Cheng, G Torigian, D Zhuang, HM Alavi, A AF Cheng, Gang Torigian, Drew A. Zhuang, Hongming Alavi, Abass TI When should we recommend use of dual time-point and delayed time-point imaging techniques in FDG PET? SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Review DE FDG; PET/CT; Dual time-point imaging; Cancer; Diagnosis ID CELL LUNG-CANCER; POSITRON-EMISSION-TOMOGRAPHY; PHASE F-18-FDG PET; LYMPH-NODE METASTASES; TUBERCULOSIS-ENDEMIC COUNTRY; SOLITARY PULMONARY NODULES; BREAST-CANCER; GALLBLADDER CARCINOMA; HEPATIC METASTASES; GLUCOSE-METABOLISM AB FDG PET and PET/CT are now widely used in oncological imaging for tumor characterization, staging, restaging, and response evaluation. However, numerous benign etiologies may cause increased FDG uptake indistinguishable from that of malignancy. Multiple studies have shown that dual time-point imaging (DTPI) of FDG PET may be helpful in differentiating malignancy from benign processes. However, exceptions exist, and some studies have demonstrated significant overlap of FDG uptake patterns between benign and malignant lesions on delayed time-point images. In this review, we summarize our experience and opinions on the value of DTPI and delayed time-point imaging in oncology, with a review of the relevant literature. We believe that the major value of DTPI and delayed time-point imaging is the increased sensitivity due to continued clearance of background activity and continued FDG accumulation in malignant lesions, if the same diagnostic criteria (as in the initial standard single time-point imaging) are used. The specificity of DTPI and delayed time-point imaging depends on multiple factors, including the prevalence of malignancies, the patient population, and the cut-off values (either SUV or retention index) used to define a malignancy. Thus, DTPI and delayed time-point imaging would be more useful if performed for evaluation of lesions in regions with significant background activity clearance over time (such as the liver, the spleen, the mediastinum), and if used in the evaluation of the extent of tumor involvement rather than in the characterization of the nature of any specific lesion. Acute infectious and non-infectious inflammatory lesions remain as the major culprit for diminished diagnostic performance of these approaches (especially in tuberculosis-endemic regions). Tumor heterogeneity may also contribute to inconsistent performance of DTPI. The authors believe that selective use of DTPI and delayed time-point imaging will improve diagnostic accuracy and interpretation confidence in FDG PET imaging. C1 [Cheng, Gang] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Cheng, Gang; Torigian, Drew A.; Alavi, Abass] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Zhuang, Hongming] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. RP Alavi, A (reprint author), Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM abass.alavi@uphs.upenn.edu NR 93 TC 49 Z9 49 U1 2 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD MAY PY 2013 VL 40 IS 5 BP 779 EP 787 DI 10.1007/s00259-013-2343-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 126NP UT WOS:000317624700017 PM 23361859 ER PT J AU Gray, PJ Fedewa, SA Shipley, WU Efstathiou, JA Lin, CC Zietman, AL Virgo, KS AF Gray, Phillip J. Fedewa, Stacey A. Shipley, William U. Efstathiou, Jason A. Lin, Chun Chieh Zietman, Anthony L. Virgo, Katherine S. TI Use of Potentially Curative Therapies for Muscle-invasive Bladder Cancer in the United States: Results from the National Cancer Data Base SO EUROPEAN UROLOGY LA English DT Article DE Bladder cancer; Genitourinary cancer; Bladder-sparing therapy; Radical cystectomy ID SOUTHWEST-ONCOLOGY-GROUP; RADICAL CYSTECTOMY; TRANSURETHRAL RESECTION; ORGAN PRESERVATION; CHEMOTHERAPY; RADIOTHERAPY; SURVIVAL; DISPARITIES; EXPERIENCE; MANAGEMENT AB Background: Despite its lethal potential, many patients with muscle-invasive bladder cancer (MIBC) do not receive aggressive, potentially curative therapy consistent with established practice standards. Objective: To characterize the treatments received by patients with MIBC and analyze their use according to sociodemographic, clinical, pathologic, and facility measures. Design, setting, and participants: Using the National Cancer Data Base, we analyzed 28 691 patients with MIBC (stages II-IV) treated between 2004 and 2008, excluding those with cT4b tumors or distant metastases. Treatments included radical or partial cystectomy with or without chemotherapy (CT), chemoradiotherapy (CRT), radiation therapy (RT), or CT alone and observation following biopsy. Aggressive therapy (AT) was defined as radical or partial cystectomy or definitive RT/CRT (total dose >= 50 Gy). Outcome measurements and statistical analysis: AT use and correlating variables were assessed by multivariable, generalized estimating equation models adjusted for facility clustering. Results and limitations: According to the database, 52.5% of patients received AT; 44.9% were treated surgically, 7.6% received definitive CRT or RT, and 25.9% of patients received observation only. AT use decreased with advancing age (odds ratio [ OR]: 0.34 for age 81-90 yr vs <= 50 yr; p < 0.001). AT use was also lower in racial minorities (OR: 0.74 for black race; p < 0.001), the uninsured (OR: 0.73; p < 0.001), Medicaid-insured patients (OR: 0.81; p = 0.01), and at low-volume centers (OR: 0.64 vs high-volume centers; p < 0.001). Use of AT was higher with increasing tumor stage (OR: 2.23 for T3/T4a vs T2; p < 0.001) and nonurothelial histology (OR: 1.25 and 1.43 for squamous and adenocarcinoma, respectively; p < 0.001). Study limitations include retrospective design and lack of information about patient and provider motivations regarding therapy selection. Conclusions: AT for MIBC appears underused, especially in the elderly and in groups with poor socioeconomic status. These data point to a significant unmet need to inform policy makers, payers, and physicians regarding appropriate therapies for MIBC. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved. * Corresponding author. Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit Street, Cox 3, Boston, MA 02114, USA. Tel. +1 617 726 8146; Fax: +1 617 726 3603. E-mail address: wshipley@partners.org (W.U. Shipley). C1 [Gray, Phillip J.; Shipley, William U.; Efstathiou, Jason A.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gray, Phillip J.] Harvard Radiat Oncol Program, Boston, MA USA. [Fedewa, Stacey A.; Lin, Chun Chieh; Virgo, Katherine S.] Amer Canc Soc, Hlth Serv Res Program, Atlanta, GA 30329 USA. [Virgo, Katherine S.] Emory Univ, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox 3, Boston, MA 02114 USA. EM wshipley@partners.org FU American Cancer Society Intramural Research Funding FX This study was supported in part by American Cancer Society Intramural Research Funding. The American Cancer Society was involved in data collection and management. NR 35 TC 57 Z9 57 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD MAY PY 2013 VL 63 IS 5 BP 823 EP 829 DI 10.1016/j.eururo.2012.11.015 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 122SC UT WOS:000317337400011 PM 23200811 ER PT J AU Nguyen, LS Kim, HG Rosenfeld, JA Shen, YP Gusella, JF Lacassie, Y Layman, LC Shaffer, LG Gecz, J AF Nguyen, Lam S. Kim, Hyung-Goo Rosenfeld, Jill A. Shen, Yiping Gusella, James F. Lacassie, Yves Layman, Lawrence C. Shaffer, Lisa G. Gecz, Jozef TI Contribution of copy number variants involving nonsense-mediated mRNA decay pathway genes to neuro-developmental disorders SO HUMAN MOLECULAR GENETICS LA English DT Article ID EXON-JUNCTION COMPLEX; MENTAL-RETARDATION; HUMAN GENOME; MICRODELETION SYNDROME; QUALITY-CONTROL; EXPRESSION; NMD; SURVEILLANCE; ABUNDANCE; YEAST AB The nonsense-mediated mRNA decay (NMD) pathway functions not only to degrade transcripts containing premature termination codons (PTC), but also to regulate the transcriptome. UPF3B and RBM8A, important components of NMD, have been implicated in various forms of intellectual disability (ID) and Thrombocytopenia with Absent Radius (TAR) syndrome, which is also associated with ID. To gauge the contribution of other NMD factors to ID, we performed a comprehensive search for copy number variants (CNVs) of 18 NMD genes among individuals with ID and/or congenital anomalies. We identified 11 cases with heterozygous deletions of the genomic region encompassing UPF2, which encodes for a direct interacting protein of UPF3B. Using RNA-Seq, we showed that the genome-wide consequence of reduced expression of UPF2 is similar to that seen in patients with UPF3B mutations. Out of the 1009 genes found deregulated in patients with UPF2 deletions by at least 2-fold, majority (95) were deregulated similarly in patients with UPF3B mutations. This supports the major role of deletion of UPF2 in ID. Furthermore, we found that four other NMD genes, UPF3A, SMG6, EIF4A3 and RNPS1 are frequently deleted and/or duplicated in the patients. We postulate that dosage imbalances of these NMD genes are likely to be the causes or act as predisposing factors for neuro-developmental disorders. Our findings further emphasize the importance of NMD pathway(s) in learning and memory. C1 [Nguyen, Lam S.; Gecz, Jozef] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA 5006, Australia. [Kim, Hyung-Goo; Shen, Yiping; Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Kim, Hyung-Goo; Shen, Yiping; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Rosenfeld, Jill A.; Shaffer, Lisa G.] PerkinElmer Inc, Signature Genom Labs, Spokane, WA 99207 USA. [Lacassie, Yves] Louisiana State Univ, Hlth Sci Ctr, Dept Paediat, Div Genet, New Orleans, LA 70118 USA. [Lacassie, Yves] Childrens Hosp, New Orleans, LA 70118 USA. [Kim, Hyung-Goo; Layman, Lawrence C.] Georgia Regents Univ, Dept Obstet & Gynaecol, Augusta, GA 30912 USA. [Gecz, Jozef] SA Pathol, Dept Genet & Mol Pathol, Adelaide, SA 5006, Australia. RP Gecz, J (reprint author), Univ Adelaide, Neurogenet Lab, Womens & Childrens Hosp, 72 King William Rd, Adelaide, SA 5006, Australia. EM jozef.gecz@adelaide.edu.au OI Gecz, Jozef/0000-0002-7884-6861 FU Wellcome Trust; Australian NHMRC [APP628952]; NH&MRC Principal Research Fellowship [APP1041920]; MS McLeod Foundation FX This study makes use of data generated by the DECIPHER Consortium. A full list of centres who contributed to the generation of the data is available from http://decipher.sanger.ac. uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust.; This work was supported by grants from the Australian NH&MRC Project Grant APP628952 to J.G. J.G. is supported by NH&MRC Principal Research Fellowship APP1041920. L.S.N.'s PhD Scholarship is supported by the MS McLeod Foundation. NR 71 TC 33 Z9 33 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2013 VL 22 IS 9 BP 1816 EP 1825 DI 10.1093/hmg/ddt035 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 123ZD UT WOS:000317431100011 PM 23376982 ER PT J AU Chu, AY Workalemahu, T Paynter, NP Rose, LM Giulianini, F Tanaka, T Ngwa, JS Qi, QB Curhan, GC Rimm, EB Hunter, DJ Pasquale, LR Ridker, PM Hu, FB Chasman, DI Qi, L AF Chu, Audrey Y. Workalemahu, Tsegaselassie Paynter, Nina P. Rose, Lynda M. Giulianini, Franco Tanaka, Toshiko Ngwa, Julius S. Qi, Qibin Curhan, Gary C. Rimm, Eric B. Hunter, David J. Pasquale, Louis R. Ridker, Paul M. Hu, Frank B. Chasman, Daniel I. Qi, Lu CA CHARGE Nutr Working Grp DietGen Consortium TI Novel locus including FGF21 is associated with dietary macronutrient intake SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; FOOD FREQUENCY QUESTIONNAIRE; INSULIN SENSITIVITY; METABOLIC SYNDROME; OBESITY; RISK; HEALTH; DISEASE; WOMEN; GENE AB Dietary intake of macronutrients (carbohydrate, protein, and fat) has been associated with risk of chronic conditions such as obesity and diabetes. Family studies have reported a moderate contribution of genetics to variation in macronutrient intake. In a genome-wide meta-analysis of a population-based discovery cohort (n 33 533), rs838133 in FGF21 (19q13.33), rs197273 near TRAF family member-associated NF-kappa-B activator (TANK) (2p24.2), and rs10163409 in FTO (16q12.2) were among the top associations (P 10(5)) for percentage of total caloric intake from protein and carbohydrate. rs838133 was replicated in silico in an independent sample from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) Nutrition Working Group (n 38 360) and attained genome-wide significance in combined analysis (P-joint 7.9 10(9)). A cytokine involved in cellular metabolism, FGF21 is a potential susceptibility gene for obesity and type 2 diabetes. Our results highlight the potential of genetic variation for determining dietary macronutrient intake. C1 [Chu, Audrey Y.; Paynter, Nina P.; Rose, Lynda M.; Giulianini, Franco; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Workalemahu, Tsegaselassie; Qi, Qibin; Curhan, Gary C.; Rimm, Eric B.; Hunter, David J.; Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Workalemahu, Tsegaselassie; Qi, Qibin; Curhan, Gary C.; Rimm, Eric B.; Hunter, David J.; Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Pasquale, Louis R.] Brigham & Womens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Chasman, Daniel I.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Workalemahu, Tsegaselassie; Qi, Qibin; Rimm, Eric B.; Hunter, David J.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Workalemahu, Tsegaselassie; Qi, Qibin; Rimm, Eric B.; Hunter, David J.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tanaka, Toshiko] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Ngwa, Julius S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Pasquale, Louis R.] Harvard Univ, Sch Med, Mass Eye & Ear Infirm, Boston, MA 02115 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Bldg 2,Room 323,655 Huntington Ave, Boston, MA 02115 USA. EM luqi@hsph.harvard.edu FU National Institutes of Health [DK091718, HL71981, HL073168, CA87969, CA49449, HL34594, HL088521, U01HG004399, DK080140, DK58845, DK46200, HL043851, HL080467, CA058988]; Amgen; American Heart Association Scientist Development Award [0730094N] FX The HPFS and NHS were supported by grants DK091718, HL71981, HL073168, CA87969, CA49449, HL34594, HL088521, U01HG004399, DK080140, DK58845 and DK46200 from the National Institutes of Health. The WGHS is supported by HL043851, HL080467 and CA058988 from the National Institutes of Health with collaborative scientific support and funding for genotyping provided by Amgen. L. Q. is a recipient of the American Heart Association Scientist Development Award (0730094N). NR 39 TC 31 Z9 33 U1 1 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2013 VL 22 IS 9 BP 1895 EP 1902 DI 10.1093/hmg/ddt032 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 123ZD UT WOS:000317431100018 PM 23372041 ER PT J AU Salgado, CD Sepkowitz, KA John, JF Cantey, JR Attaway, HH Freeman, KD Sharpe, PA Michels, HT Schmidt, MG AF Salgado, Cassandra D. Sepkowitz, Kent A. John, Joseph F. Cantey, J. Robert Attaway, Hubert H. Freeman, Katherine D. Sharpe, Peter A. Michels, Harold T. Schmidt, Michael G. TI Copper Surfaces Reduce the Rate of Healthcare-Acquired Infections in the Intensive Care Unit SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; NOSOCOMIAL PATHOGENS; CLOSTRIDIUM-DIFFICILE; MICROBIAL BURDEN; ENVIRONMENT; RISK; CONTAMINATION; SURVEILLANCE; TRANSMISSION; ENTEROCOCCUS AB OBJECTIVE. Healthcare-acquired infections (HAIs) cause substantial patient morbidity and mortality. Items in the environment harbor microorganisms that may contribute to HAIs. Reduction in surface bioburden may be an effective strategy to reduce HAIs. The inherent biocidal properties of copper surfaces offer a theoretical advantage to conventional cleaning, as the effect is continuous rather than episodic. We sought to determine whether placement of copper alloy-surfaced objects in an intensive care unit (ICU) reduced the risk of HAI. DESIGN. Intention-to-treat randomized control trial between July 12, 2010, and June 14, 2011. SETTING. The ICUs of 3 hospitals. PATIENTS. Patients presenting for admission to the ICU. METHODS. Patients were randomly placed in available rooms with or without copper alloy surfaces, and the rates of incident HAI and/or colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in each type of room were compared. RESULTS. The rate of HAI and/or MRSA or VRE colonization in ICU rooms with copper alloy surfaces was significantly lower than that in standard ICU rooms (0.071 vs 0.123; P = .020). For HAI only, the rate was reduced from 0.081 to 0.034 (P = .013). CONCLUSIONS. Patients cared for in ICU rooms with copper alloy surfaces had a significantly lower rate of incident HAI and/or colonization with MRSA or VRE than did patients treated in standard rooms. Additional studies are needed to determine the clinical effect of copper alloy surfaces in additional patient populations and settings. Infect Control Hosp Epidemiol 2013;34(5):479-486 C1 [Salgado, Cassandra D.; Cantey, J. Robert] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Sepkowitz, Kent A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [John, Joseph F.] Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC USA. [Attaway, Hubert H.; Schmidt, Michael G.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Freeman, Katherine D.] Extrapolate LLC, Delray Beach, FL USA. [Sharpe, Peter A.] Sharpe & Associates, W Orange, NJ USA. [Michels, Harold T.] Copper Dev Assoc, New York, NY USA. RP Salgado, CD (reprint author), Div Infect Dis, 135 Rutledge Ave, Charleston, SC 29425 USA. EM salgado@musc.edu OI Schmidt, Michael G/0000-0002-7794-7265 FU US Army Materiel Command, US Department of Defense (DOD) [W81XWH-07-C-0053] FX This study was funded by a grant from the US Army Materiel Command, US Department of Defense (DOD; contract W81XWH-07-C-0053). The funding source was not involved in the preparation, submission, and review of the manuscript. NR 36 TC 87 Z9 90 U1 1 U2 48 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 2013 VL 34 IS 5 SI SI BP 479 EP 486 DI 10.1086/670207 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 123XC UT WOS:000317424200006 PM 23571364 ER PT J AU Bernstein, KD Sethi, R Trofimov, A Zeng, C Fullerton, B Yeap, BY Ebb, D Tarbell, NJ Yock, TI MacDonald, SM AF Bernstein, Karen De Amorim Sethi, Roshan Trofimov, Alexei Zeng, Chuan Fullerton, Barbara Yeap, Beow Y. Ebb, David Tarbell, Nancy J. Yock, Torunn I. MacDonald, Shannon M. TI Early Clinical Outcomes Using Proton Radiation for Children With Central Nervous System Atypical Teratoid Rhabdoid Tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID TERATOID/RHABDOID TUMOR; BRAIN-TUMORS; CHEMOTHERAPY; RADIOTHERAPY; CHILDHOOD; SURVIVAL; THERAPY; PATIENT; MEDULLOBLASTOMA; IRRADIATION AB Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive tumor that often affects infants. Irradiation improves survival but has traditionally been avoided in patients under the age of 3 due to the increasing risk of neurocognitive side effects. We report the first cohort of AT/RT patients treated with proton therapy. Methods and Materials: All patients with AT/RT treated at Massachusetts General Hospital (MGH) Frances H. Burr Proton Beam Therapy Benter between July 2004 and November 2011 were included in this study. All patients were treated with 3-dimensional conformal proton therapy (3D-CPT). Results: Ten consecutive patients of a median 2.3 years of age and with a median follow-up of 27.3 months (range, 11.3-99.4 months) were identified. Two patients suffered distant relapse; 1 patient was successfully treated with involved field irradiation and chemotherapy, while the second patient died of disease. At last follow-up, 9 patients were alive without evidence of disease. Proton radiation demonstrated increasing sparing of the cerebrum, temporal lobe, cochlea, and hypothalamus. Conclusions: Initial clinical outcomes with proton therapy are favorable. The advantages of proton therapy are particularly suited to the treatment of AT/RT, a tumor that often requires irradiation treatment at an age when avoiding irradiation to healthy tissues is most desirable. (C) 2013 Elsevier Inc. C1 [Bernstein, Karen De Amorim; Sethi, Roshan; Trofimov, Alexei; Zeng, Chuan; Tarbell, Nancy J.; Yock, Torunn I.; MacDonald, Shannon M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Ebb, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Hematol Oncol, Boston, MA USA. [Fullerton, Barbara] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP MacDonald, SM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Yawkey 112,55 Fruit St, Boston, MA 02114 USA. EM smacdonald@partners.org NR 22 TC 5 Z9 6 U1 2 U2 5 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 MAY 1 PY 2013 VL 86 IS 1 BP 114 EP 120 DI 10.1016/j.ijrobp.2012.12.004 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 122VH UT WOS:000317345700026 ER PT J AU Russo, AL Chen, YH Martin, NE Vinjamoori, A Luthy, SK Freedman, A Michaelson, EM Silver, B Mauch, PM Ng, AK AF Russo, Andrea L. Chen, Yu-Hui Martin, Neil E. Vinjamoori, Anant Luthy, Sarah K. Freedman, Arnold Michaelson, Evan M. Silver, Barbara Mauch, Peter M. Ng, Andrea K. TI Low-Dose Involved-Field Radiation in the Treatment of Non-Hodgkin Lymphoma: Predictors of Response and Treatment Failure SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID INDOLENT LYMPHOMAS; LOCAL RADIOTHERAPY AB Purpose: To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin lymphoma (NHL). Methods and Materials: Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazards regression model was used to assess time to further treatment. Results: We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 ;months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age <= 50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio [HR] 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001). Conclusions: High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age <= 50 years at diagnosis had a shorter time to further treatment after LD-IFRT. (C) 2013 Elsevier Inc. C1 [Russo, Andrea L.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Biostat Core, Boston, MA 02115 USA. [Martin, Neil E.; Vinjamoori, Anant; Luthy, Sarah K.; Michaelson, Evan M.; Silver, Barbara; Mauch, Peter M.; Ng, Andrea K.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Freedman, Arnold] Brigham & Womens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Russo, AL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM alrusso@partners.org RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 20 TC 9 Z9 9 U1 0 U2 2 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 MAY 1 PY 2013 VL 86 IS 1 BP 121 EP 127 DI 10.1016/j.ijrobp.2012.12.024 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 122VH UT WOS:000317345700027 PM 23414765 ER PT J AU Min, CH Zhu, XP Winey, BA Grogg, K Testa, M El Fakhri, G Bortfeld, TR Paganetti, H Shih, HA AF Min, Chul Hee Zhu, Xuping Winey, Brian A. Grogg, Kira Testa, Mauro El Fakhri, Georges Bortfeld, Thomas R. Paganetti, Harald Shih, Helen A. TI Clinical Application of In-Room Positron Emission Tomography for In Vivo Treatment Monitoring in Proton Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID BEAM THERAPY; PET; RANGE; IMPLEMENTATION; UNCERTAINTIES; VERIFICATION; IRRADIATION AB Purpose: The purpose of this study is to evaluate the potential of using in-room positron emission tomography (PET) for treatment verification in proton therapy and for deriving suitable PET scan times. Methods and Materials: Nine patients undergoing passive scattering proton therapy underwent scanning immediately after treatment with an in-room PET scanner. The scanner was positioned next to the treatment head after treatment. The Monte Carlo (MC) method was used to reproduce PET activities for each patient. To assess the proton beam range uncertainty, we designed a novel concept in which the measured PET activity surface distal to the target at the end of range was compared with MC predictions. The repositioning of patients for the PET scan took, on average, approximately 2 minutes. The PET images were reconstructed considering varying scan times to test the scan time dependency of the method. Results: The measured PET images show overall good spatial correlations with MC predictions. Some discrepancies could be attributed to uncertainties in the local elemental composition and biological washout. For 8 patients treated with a single field, the average range differences between PET measurements and computed tomography (CT) image-based MC results were <5 mm (<3 mm for 6 of 8 patients) and root-mean-square deviations were 4 to 11 mm with PET-CT image co-registration errors of approximately 2 mm. Our results also show that a short-length PET scan of 5 minutes can yield results similar to those of a 20-minute PET scan. Conclusions: Our first clinical trials in 9 patients using an in-room PET system demonstrated its potential for in vivo treatment monitoring in proton therapy. For a quantitative range prediction with arbitrary shape of target volume, we suggest using the distal PET activity surface. (C) 2013 Elsevier Inc. C1 [Min, Chul Hee; Winey, Brian A.; Testa, Mauro; Bortfeld, Thomas R.; Paganetti, Harald; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Min, Chul Hee; Winey, Brian A.; Testa, Mauro; Bortfeld, Thomas R.; Paganetti, Harald; Shih, Helen A.] Harvard Univ, Sch Med, Boston, MA USA. [Zhu, Xuping; Grogg, Kira; El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Radiol Sci Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM hshih@partners.org FU National Cancer Institute [P01CA21239, R21CA153455]; National Institute of Biomedical Imaging and Bioengineering [R21EB12823] FX This work was supported by grants P01CA21239 "Proton Therapy Research" and R21CA153455 (Principal Investigator [PI]: G. El Fakhri) from the National Cancer Institute, and R21EB12823 (PI: G. El Fakhri) from the National Institute of Biomedical Imaging and Bioengineering. NR 17 TC 28 Z9 29 U1 0 U2 9 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 MAY 1 PY 2013 VL 86 IS 1 BP 183 EP 189 DI 10.1016/j.ijrobp.2012.12.010 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 122VH UT WOS:000317345700036 PM 23391817 ER PT J AU Chonde, DB Abolmaali, N Arabasz, G Guimaraes, AR Catana, C AF Chonde, Daniel B. Abolmaali, Nasreddin Arabasz, Grae Guimaraes, Alexander R. Catana, Ciprian TI Effect of MRI Acoustic Noise on Cerebral Fludeoxyglucose Uptake in Simultaneous MR-PET Imaging SO INVESTIGATIVE RADIOLOGY LA English DT Article DE PET; MRI; multimodality imaging; physiological interference; auditory cortex ID POSITRON-EMISSION-TOMOGRAPHY; TRANSCRANIAL MAGNETIC STIMULATION; AUDITORY-CORTEX; ATTENUATION-CORRECTION; INFERIOR COLLICULUS; HUMAN BRAIN; FMRI; GLUCOSE; CONNECTIVITY; REGISTRATION AB Integrated scanners capable of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) data acquisition are now available for human use. Although the scanners' manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the 2 modalities, the potential physiological inference has not been evaluated. In this study, we have studied the influence of the acoustic noise produced by the magnetic resonance (MR) gradients on brain fludeoxyglucose (FDG) uptake in the Siemens MR-BrainPET prototype. Although particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed. Methods: The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, 10 healthy volunteers underwent 2 simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a "quiet" (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a "noisy" (test) environment in which MR sequences were run for the entire time. Cortical and subcortical regions of interest were derived from the high-resolution morphological MR data using FreeSurfer. The changes in the FDG uptake in the FreeSurfer-derived regions of interest between the 2 conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer. Results: Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The region of interest-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13% [4.73%]) and static (4.18% [2.87%]) images. The SPM8 analysis showed no statistically significant clusters in any images when a P < 0.05 (corrected) was used; however, a P < 0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left, 8.37% [1.55%]; right, 8.20% [1.17%]) but only unilateral increase in the static image (left, 8.68% [3.89%]). Conclusions: Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in the FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation-related) changes in the FDG uptake in this region if the expected effects are of comparable amplitude. C1 [Chonde, Daniel B.; Arabasz, Grae; Guimaraes, Alexander R.; Catana, Ciprian] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Chonde, Daniel B.; Arabasz, Grae; Guimaraes, Alexander R.; Catana, Ciprian] Harvard Univ, Sch Med, Charlestown, MA USA. [Chonde, Daniel B.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. [Abolmaali, Nasreddin] Univ Clin Carl Gustav Carus, OncoRay Natl Ctr Radiat Res Oncol, Dresden, Germany. RP Chonde, DB (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM chonde@nmr.mgh.harvard.edu FU National Institutes of Health, Bethesda, MD [R01CA137254-01A1, 5T32GM008313, 5T90DA022759-05, T32EB001680] FX Supported by grants R01CA137254-01A1, 5T32GM008313, 5T90DA022759-05, and T32EB001680 from the National Institutes of Health, Bethesda, MD. NR 38 TC 9 Z9 9 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD MAY PY 2013 VL 48 IS 5 BP 302 EP 312 DI 10.1097/RLI.0b013e3182839fbc PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 125ZO UT WOS:000317581100010 PM 23462677 ER PT J AU Borus, JS Blood, E Volkening, LK Laffel, L Shrier, LA AF Borus, Joshua S. Blood, Emily Volkening, Lisa K. Laffel, Lori Shrier, Lydia A. TI Momentary Assessment of Social Context and Glucose Monitoring Adherence in Adolescents With Type 1 Diabetes SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Type 1 diabetes; Momentary sampling; Adolescents; Adherence; Social context ID GLYCEMIC CONTROL; SELF-CARE; SUPPORT; MELLITUS; MANAGEMENT; SITUATIONS; FRIENDS; YOUTH AB Purpose: To investigate the associations between momentary social context and glucose monitoring adherence in adolescents with type 1diabetes (T1D). Methods: For 14 days, patients (14-18 years old, T1D duration >1 year) of a pediatric diabetes clinic carried handheld computers that prompted them to report their location, companionship, and attitudes toward companions at the times they usually checked their glucose, and again 30 minutes later to report whether they checked their glucose and, if not, why. Associations between social context factors and checking glucose (adherence) were analyzed using logistic generalized estimating equations and adjusted for age, sex, duration of T1D, and pump use. Results: Thirty-six participants (mean age 16.6 +/- 1.5 years, mean duration of T1D 8.7 +/- 4.4 years) completed 971 context and 1,210 adherence reports, resulting in 805 paired reports. Median signal response rate was 63%. The odds of checking glucose was higher when participants expressed very strong desire to blend in (adjusted odds ratio [AOR] = 2.30, 95% confidence interval 1.07-4.94, p = .03). Strong desire to impress others was associated with decreased likelihood of checking glucose (AOR = .52, 95% confidence interval .28-.97, p = .04.) Location, solitude, type of companion, and attitudes toward companions were not significantly associated with checking glucose. Conclusions: Desire to blend in may support glucose monitoring adherence and desire to impress others may impede this behavior in adolescents with T1D. Other dimensions of social context were not linked to checking glucose in this study. (C) 2013 Society for Adolescent Health and Medicine. All rights reserved. C1 [Borus, Joshua S.; Shrier, Lydia A.] Boston Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA 02115 USA. [Blood, Emily] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Borus, Joshua S.; Blood, Emily; Laffel, Lori; Shrier, Lydia A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Volkening, Lisa K.; Laffel, Lori] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Laffel, Lori] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Borus, JS (reprint author), Boston Childrens Hosp, Div Adolescent Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. EM Joshua.borus@childrens.harvard.edu FU Leadership Education in Adolescent Health (LEAH) from the Maternal and Child Health Bureau [T71MC00009]; Division of Adolescent/Young Adult Medicine at Boston Children's Hospital; Katherine Adler Astrove Youth Education Fund at the Joslin Diabetes Center; Eleanor Chesterman Beatson Youth Fund; Maria Griffin Drury Pediatric Fund at the Joslin Diabetes Center FX This work was supported in part by the Leadership Education in Adolescent Health (LEAH) training grant no. T71MC00009 from the Maternal and Child Health Bureau and a Gallagher Award from the Division of Adolescent/Young Adult Medicine at Boston Children's Hospital. The Katherine Adler Astrove Youth Education Fund at the Joslin Diabetes Center, Eleanor Chesterman Beatson Youth Fund, and the Maria Griffin Drury Pediatric Fund at the Joslin Diabetes Center also provided support. Portions of this manuscript were presented at the 2012 Annual Meeting of the Society for Adolescent Health and Medicine. NR 26 TC 5 Z9 5 U1 2 U2 4 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 MAY PY 2013 VL 52 IS 5 BP 578 EP 583 DI 10.1016/j.jadohealth.2012.10.003 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 126ZD UT WOS:000317661300013 PM 23298986 ER PT J AU Biederman, J Martelon, M Faraone, SV Woodworth, KY Spencer, TJ Wozniak, JR AF Biederman, Joseph Martelon, MaryKate Faraone, Stephen V. Woodworth, K. Yvonne Spencer, Thomas J. Wozniak, Janet R. TI Personal and familial correlates of bipolar (BP)-I disorder in children with a diagnosis of BP-I disorder with a positive child behavior checklist (CBCL)-severe dysregulation profile: A controlled study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Mood disorders; Severity of illness index; Screening instrument ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EMOTIONAL SELF-REGULATION; ADHD; CBCL; COMORBIDITY; MANIA; METAANALYSIS; PREVALENCE; YOUTH AB Background: Although the DSM-IV provides explicit criteria for the diagnosis of BP-I disorder, this is a complex diagnosis that requires high levels of clinical expertise. Previous work shows children with a unique profile of the CBCL of high scores (2SD) on the attention problems (AP), aggressive behavior (AGG), and anxious-depressed (AD) (A-A-A) subscales are more likely than other children to meet criteria for BP-I disorder in both epidemiological and clinical samples. However, since not all BP-I disorder children have a positive profile questions remain as to its informativeness, particularly in the absence of an expert diagnostician. Methods: Analyses were conducted comparing personal and familial correlates of BP-I disorder in 140 youth with a structured interview and an expert clinician based DSM-IV diagnosis of BP-I disorder with (N=80) and without (N=60) a positive CBCL- Severe Dysregulation profile, and 129 controls of similar age and sex without ADHD or a mood disorder. Subjects were comprehensively assessed with structured diagnostic interviews and wide range of functional measures. We defined the CBCL-severe dysregulation profile as an aggregate cut-off score of >= 210 on the A-A-A scales. Results: BP-I probands with and without a positive CBCL-severe dysregulation profile significantly differed from Controls in patterns of psychiatric comorbidity, psychosocial and psychoeducational dysfunction, and cognitive deficits, as well as in their risk for BP-I disorder in first degree relatives. Limitations: Because the sample was referred and largely Caucasian, findings may not generalize to community samples and other ethnic groups. Conclusion: A positive CBCL-severe dysregulation profile identifies a severe subgroup of BP-I disorder youth. (C) 2012 Elsevier B.V. All rights reserved. C1 [Biederman, Joseph; Martelon, MaryKate; Woodworth, K. Yvonne; Spencer, Thomas J.; Wozniak, Janet R.] Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Martelon, MaryKate; Woodworth, K. Yvonne; Spencer, Thomas J.; Wozniak, Janet R.] Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas J.; Wozniak, Janet R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 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, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIH [K08MH001503, R01MH066237, R01MH050657, R01HD036317]; Heinz C. Prechter Bipolar Research Fund; Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder FX This work was supported by NIH grants K08MH001503 and R01MH066237 to Dr Wozniak and R01MH050657 and R01HD036317 to Dr Biederman. This work was also supported by a grant from the Heinz C. Prechter Bipolar Research Fund, the support of members of the MGH Pediatric Psychopharmacology Council, and the Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder. NR 34 TC 12 Z9 12 U1 4 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 2013 VL 147 IS 1-3 BP 164 EP 170 DI 10.1016/j.jad.2012.10.028 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 115CQ UT WOS:000316790400024 PM 23164462 ER PT J AU Townsend, JD Sugar, CA Walshaw, PD Vasquez, RE Foland-Ross, LC Moody, TD Bookheimer, SY McGough, JJ Altshuler, LL AF Townsend, Jennifer D. Sugar, Catherine A. Walshaw, Patricia D. Vasquez, Roxanne E. Foland-Ross, Lara C. Moody, Teena D. Bookheimer, Susan Y. McGough, James J. Altshuler, Lori L. TI Frontostriatal neuroimaging findings differ in patients with bipolar disorder who have or do not have ADHD comorbidity SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Euthymia; fMRI; ADHD; Response inhibition; Inferior frontal cortex ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; RESPONSE-INHIBITION; PREFRONTAL CORTEX; COGNITIVE CONTROL; BRAIN ACTIVATION; CINGULATE CORTEX; DEPRESSION; MANIA; CONNECTIVITY AB Background: The inferior frontal cortical (IFC)-striatal network plays an integral role in response inhibition and is compromised in patients with Bipolar Disorder (BP) or Attention-Deficit/Hyperactivity Disorder (ADHD). Prior BP functional neuroimaging studies have not accounted for ADHD comorbidity despite its high prevalence. Methods: The authors conducted an fMRI study using a response inhibition task (Go-NoGo) in 32 euthymic adults with BP, half with comorbid ADHD (BP/ADHD); 16 adults with ADHD alone; and 30 healthy controls. Within- and between-group whole-brain analyses were performed to assess for significant neural function differences. Results: All groups activated frontal and striatal regions involved in response inhibition. ANOVA results demonstrated significant interaction effects of BP and ADHD in the anterior and posterior cingulate, left superior and middle frontal gyri and left inferior parietal lobule. Follow-up comparisons showed significant differences between BP subjects with and without ADHD. Other regions demonstrated main effects of BP (left inferior frontal gyms, left middle frontal gyms, right superior frontal gyrus and left insula) and ADHD (left inferior frontal gyms, left precentral gyrus and right anterior cingulate). Limitations: This study, as the first of its kind, requires replication using large sample sizes and controlling for potential effects of medication. Conclusions: Euthymic bipolar adults with comorbid ADHD have significantly different neural activation patterns from BP patients without this comorbidity. If understanding of the neurobiology of bipolar disorder is to be achieved, it is critical to control for this potential confound, something not done by most prior fMRI studies of adults with BP. Published by Elsevier B.V. C1 [Townsend, Jennifer D.; Sugar, Catherine A.; Walshaw, Patricia D.; Vasquez, Roxanne E.; Moody, Teena D.; Bookheimer, Susan Y.; McGough, James J.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Sugar, Catherine A.; Moody, Teena D.; McGough, James J.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Foland-Ross, Lara C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] West Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, Mood Disorders Res Program, 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU Furlotti Family Foundation; National Institutes of Health (NIH): National Institute of Mental Health [K24 MH001848, R21 MH075944, 5F31MH078556]; National Institutes of Health (NIH): National Center for Research Resources (NCRR) [RR12169, RR13642, RR00865]; Abbott Laboratories; Eli Lilly; NeuroSigma Inc.; Supranus; Shionogi Pharmaceuticals FX This study was supported by the Furlotti Family Foundation and the following two components of the National Institutes of Health (NIH): the National Institute of Mental Health (K24 MH001848 (LA), R21 MH075944 (LA), 5F31MH078556 (LF)) and the National Center for Research Resources (NCRR) (RR12169, RR13642 and RR00865).; Drs. Bookheimer, Foland-Ross, Moody and Sugar, Ms. Townsend and Ms. Vasquez report no financial relationships with commercial interests. Dr. Altshuler has received research support from Abbott Laboratories; consulting honoraria from Eli Lilly, Abbott Laboratories, Forest Laboratories and Sepracor; and speakers bureau honoraria from Forest Laboratories, GlaxoSmith Kline, Bristol Meyer Squibb/Otsuka America.; Dr. McGough has received consulting honoraria from Eli Lilly & Co., MedImmune, Shionogi Pharmaceuticals, Shire, Sunovion, and Targacept, and research support from Eli Lilly, NeuroSigma Inc., Supranus and Shionogi Pharmaceuticals. None of the above affiliations should result in a conflict of interest related to the subject of the manuscript being submitted. NR 41 TC 5 Z9 6 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 2013 VL 147 IS 1-3 BP 389 EP 396 DI 10.1016/j.jad.2012.08.019 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 115CQ UT WOS:000316790400056 PM 23057969 ER PT J AU Bakhru, MR Sethi, A Jamidar, PA Singh, SK Kwon, RS Siddiqui, UD Sawhney, M Talreja, JP Kline, P Malik, U Gaidhane, M Sauer, BG Kahaleh, M AF Bakhru, Mihir R. Sethi, Amrita Jamidar, Priya A. Singh, Satish K. Kwon, Richard S. Siddiqui, Uzma D. Sawhney, Mandeep Talreja, Jayant P. Kline, Pamela Malik, Umer Gaidhane, Monica Sauer, Bryan G. Kahaleh, Michel TI Interobserver Agreement for Confocal Imaging of Ampullary Lesions A Multicenter Single-blinded Study SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE probe-based confocal laser endomicroscopy; ampullary lesions; interobserver agreement; pCLE ID LASER ENDOMICROSCOPY; ULCERATIVE-COLITIS; TUMORS; DIAGNOSIS; NEOPLASIA; ACCURACY; BIOPSY AB Background: Malignant ampullary lesions can be difficult to classify by endoscopy alone. Probe-based confocal laser endomicroscopy (pCLE) permits in vivo assessment of mucosal structures in the gastrointestinal tracts in the real time. Aim: The objective of this pilot multicenter study was to assess the interobserver agreement and variance in interpretation of pCLE of ampullary lesions. Methods: Twelve pCLE video clips of ampullary lesions were distributed to 6 gastrointestinal specialists at 5 medical centers, blinded to final pathologic results. Six variables were assessed for interobserver agreement using kappa statistics. Variables included an epithelial outer border with irregular thickness, dark epithelium without discernable individual cells, heterogenously distributed elongated crypts, reduced number of goblet cells, neovascularization, and final diagnosis. Results: The overall interobserver agreement for all observers was poor to slight for all variables (kappa = 0.02, 0.05, -0.01, 0.04, 0.018) except for the first variable with fair degree of agreement (kappa = 0.27). On the basis of experience, 3 observers were classified as less experienced, whereas 3 were classified as most experienced. Upon stratification, the less experienced observers had poor interobserver agreement for all variables, except 1. The most experienced observers had poor agreement for 2 variables, slight agreement for 3 variables, and fair agreement for the final diagnosis variable. Conclusions: The overall interpersonal agreement on pCLE for ampullary lesions was poor. The interobserver agreement was not substantially improved for experienced raters. Further standardization of pCLE image criteria is needed for ampullary lesions. Standardized training may improve interrater reliability to an acceptable level. C1 [Bakhru, Mihir R.; Talreja, Jayant P.; Sauer, Bryan G.] Univ Virginia, Dept Digest Hlth, Charlottesville, VA USA. [Sethi, Amrita] Columbia Univ, Med Ctr, Dept Gastroenterol, New York, NY USA. [Kline, Pamela; Malik, Umer; Gaidhane, Monica; Kahaleh, Michel] Weill Cornell Med Coll, Dept Med, Div Gastroenterol & Hepatol, New York, NY USA. [Jamidar, Priya A.; Siddiqui, Uzma D.] Yale Univ, Dept Gastroenterol, New Haven, CT USA. [Singh, Satish K.] Boston Univ, Sch Med, Dept Gastroenterol, Boston, MA 02118 USA. [Sawhney, Mandeep] BIDMC, Dept Gastroenterol, Boston, MA USA. [Kwon, Richard S.] Univ Michigan, Dept Gastroenterol, Ann Arbor, MI 48109 USA. RP Kahaleh, M (reprint author), Weill Cornell Med Coll, Pancreas Program, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10021 USA. EM mkahaleh@gmail.com RI Gaidhane, Monica/B-9414-2009 OI Gaidhane, Monica/0000-0001-6773-7080 NR 20 TC 7 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2013 VL 47 IS 5 BP 440 EP 442 DI 10.1097/MCG.0b013e3182745f2b PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 124PO UT WOS:000317477400017 PM 23340063 ER PT J AU Amorosa, VK Aibana, O Shire, NJ Dorey-Stein, Z Ferrara, T Gilmore, J Kostman, JR Lo Re, V AF Amorosa, Valerianna K. Aibana, Omowunmi Shire, Norah J. Dorey-Stein, Zachariah Ferrara, Thomas Gilmore, Joanne Kostman, Jay R. Lo Re, Vincent TI Willingness to Undergo a Repeat Liver Biopsy Among HIV/Hepatitis C Virus-coinfected and Hepatitis C Virus-monoinfected Patients SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE liver biopsy; hepatitis C; HIV/hepatitis C coinfection; HIV; staging of fibrosis ID FIBROSIS PROGRESSION AB Background: Guidelines for chronic hepatitis C virus (HCV) management have recommended that a liver biopsy be repeated at 3-year intervals for HIV/HCV-coinfected patients and 5-year intervals for those with HCV monoinfection to assess fibrosis progression. However, it is unclear if patients are willing to repeat this procedure. Objective: To determine the prevalence and factors, particularly HIV coinfection, associated with willingness to repeat a liver biopsy. Methods: A questionnaire was administered to 235 HCV-infected patients (113 with HIV coinfection) between January 2008 and June 2011 who previously underwent liver biopsy. The main outcome was self-reported willingness to repeat the biopsy. The questionnaire collected data on other hypothesized determinants of willingness to repeat the biopsy. These were evaluated by logistic regression. Results: Among 235 subjects who completed the questionnaire, 32 (14%) reported unwillingness to repeat the biopsy, most commonly because of a perception that it was unimportant for care [13(41%)], concerns regarding pain [12(38%)], and a poor experience with the prior biopsy [7(21%)]. Considering biopsy to be safe [odds ratio (OR), 4.45; 95% CI, 1.50-13.27], important (OR, 4.87; 95% CI, 1.83-12.95), and knowing a person who underwent liver biopsy (OR, 3.45; 95% CI, 1.16-10.23) were associated with willingness to repeat the biopsy. HIV was not associated with willingness to repeat the biopsy (OR, 1.42; 95% CI, 0.67-3.03). Conclusions: Eighty-six percent of chronic HCV-infected patients were willing to repeat a liver biopsy. HIV was not associated with unwillingness. In patients in whom a repeat liver biopsy is indicated, education on the utility and safety of the biopsy is important to its acceptance. C1 [Amorosa, Valerianna K.; Lo Re, Vincent] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Amorosa, Valerianna K.; Dorey-Stein, Zachariah; Ferrara, Thomas; Gilmore, Joanne; Kostman, Jay R.; Lo Re, Vincent] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Shire, Norah J.; Lo Re, Vincent] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Aibana, Omowunmi] Harvard Univ, Sch Med, Boston, MA USA. [Shire, Norah J.] Merck & Co Inc, Whitehouse Stn, NJ 08889 USA. RP Amorosa, VK (reprint author), Philadelphia VAMC, Infect Dis Sect, Dept Med, Philadelphia, PA 19104 USA. EM valerianna.amorosa@uphs.upenn.edu RI Lo Re, Vincent/N-7817-2015 FU National Institutes of Health Research [K01 AI070001] FX V.L.R. was financially supported by the National Institutes of Health Research Grant K01 AI070001. NR 8 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2013 VL 47 IS 5 BP 457 EP 460 DI 10.1097/MCG.0b013e318266fe70 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 124PO UT WOS:000317477400020 PM 23328300 ER PT J AU Pollock, NR Macovei, L Kanunfre, K Dhiman, R Restrepo, BI Zarate, I Pino, PA Mora-Guzman, F Fujiwara, RT Michel, G Kashino, SS Campos-Neto, A AF Pollock, Nira R. Macovei, Lilia Kanunfre, Kelly Dhiman, Rakesh Restrepo, Blanca I. Zarate, Izelda Pino, Paula A. Mora-Guzman, Francisco Fujiwara, Ricardo T. Michel, Gerd Kashino, Suely S. Campos-Neto, Antonio TI Validation of Mycobacterium tuberculosis Rv1681 Protein as a Diagnostic Marker of Active Pulmonary Tuberculosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SMEAR MICROSCOPY; URINE; IDENTIFICATION; BIOMARKERS; SPECIMENS; NEEDS; LAM; DNA AB The development of an accurate antigen detection assay for the diagnosis of active tuberculosis (TB) would represent a major clinical advance. Here, we demonstrate that the Mycobacterium tuberculosis Rv1681 protein is a biomarker for active TB with potential diagnostic utility. We initially identified, by mass spectroscopy, peptides from the Rv1681 protein in urine specimens from 4 patients with untreated active TB. Rabbit IgG anti-recombinant Rv1681 detected Rv1681 protein in lysates and culture filtrates of M. tuberculosis and immunoprecipitated it from pooled urine specimens from two TB patients. An enzyme-linked immunosorbent assay formatted with these antibodies detected Rv1681 protein in unconcentrated urine specimens from 11/25 (44%) TB patients and 1/21 (4.8%) subjects in whom TB was initially clinically suspected but then ruled out by conventional methods. Rv1681 protein was not detected in urine specimens from 10 subjects with Escherichia coli-positive urine cultures, 26 subjects with confirmed non-TB tropical diseases (11 with schistosomiasis, 5 with Chagas' disease, and 10 with cutaneous leishmaniasis), and 14 healthy subjects. These results provide strong validation of Rv1681 protein as a promising biomarker for TB diagnosis. C1 [Pollock, Nira R.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Macovei, Lilia; Kanunfre, Kelly; Dhiman, Rakesh; Kashino, Suely S.; Campos-Neto, Antonio] Forsyth Inst, Global Infect Dis Res Ctr, Cambridge, MA USA. [Restrepo, Blanca I.; Zarate, Izelda; Pino, Paula A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Brownsville, TX USA. [Mora-Guzman, Francisco] Secretaria Salud Tamaulipas, Matamoros, Mexico. [Fujiwara, Ricardo T.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Michel, Gerd] Fdn Innovat New Diagnost, Geneva, Switzerland. RP Pollock, NR (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. EM nira.pollock@childrens.harvard.edu; acampos@forsyth.org RI Fujiwara, Ricardo/J-7579-2012 OI Fujiwara, Ricardo/0000-0002-4713-575X FU Foundation for Innovative New Diagnostics (FIND); Bill and Melinda Gates Foundation [OPP1039610]; National Institutes of Health [R01 AI076425, K23 AI074638]; Harvard Catalyst; Pittsfield Anti-Tuberculosis Association FX This work was supported by grants from the Foundation for Innovative New Diagnostics (FIND) (to A.C.-N.), the Bill and Melinda Gates Foundation (grant OPP1039610 to A.C.-N. and N.R.P.), the National Institutes of Health (grant R01 AI076425 to A.C.-N. and grant K23 AI074638 to N.R.P.), Harvard Catalyst (pilot grant to N.R.P.), and the Pittsfield Anti-Tuberculosis Association (to N.R.P.). NR 25 TC 8 Z9 8 U1 0 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2013 VL 51 IS 5 BP 1367 EP 1373 DI 10.1128/JCM.03192-12 PG 7 WC Microbiology SC Microbiology GA 126GT UT WOS:000317602100004 PM 23390284 ER PT J AU Lysaght, S Ersek, M AF Lysaght, Susan Ersek, Mary TI Settings of Care Within Hospice New Options and Questions About Dying "At Home" SO JOURNAL OF HOSPICE & PALLIATIVE NURSING LA English DT Article DE caregiving; hospice; inpatient hospice; place of death ID FACTORS INFLUENCING DEATH; LIFE CANCER CARE; NO PLACE LIKE; OF-LIFE; FAMILY CAREGIVERS; HOSPITALIZED-PATIENTS; PEOPLE DIE; END; DETERMINANTS; PERSPECTIVES AB Although place of death has been routinely studied in end-of-life care, more analysis on place of death within hospice is needed because of the recent, dramatic rise in the number of hospice patients dying in inpatient settings. Using a case study to illustrate the complexity of determinants of place of death within hospice, this article highlights important known factors and elucidates gaps for further research. Individual- and system-level factors, sociocultural meanings, caregiving, and preferences are shown to have important implications. Additionally, the unique components of home hospice, inpatient hospice, and transitions between these settings may have a fundamental role in the future of quality end-of-life care. Further research on determinants of hospice settings of care is essential to the care of older adults at the end of life. C1 [Lysaght, Susan; Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Ersek, Mary] Philadelphia Vet Affairs Med Ctr, Natl PROMISE Performance Reporting & Outcomes Mea, Philadelphia, PA USA. RP Lysaght, S (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,310g,418 Curie Blvd, Philadelphia, PA 19104 USA. EM slysaght@nursing.upenn.edu FU John A. Hartford Building Academic Geriatric Nursing Capacity Scholar Award; Ruth L. Kirschstein Individual NRSA Predoctoral Fellowship [1F31NR013103]; NINR Individualized Care for At-Risk Older Adults [T32NR009356] FX Dr Lysaght was supported by a John A. Hartford Building Academic Geriatric Nursing Capacity Scholar Award 2010-2012 and a Ruth L. Kirschstein Individual NRSA Predoctoral Fellowship (1F31NR013103); Dr Lysaght also received funding through NINR T32NR009356 Individualized Care for At-Risk Older Adults from 2008 to 2010. NR 40 TC 5 Z9 5 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1522-2179 J9 J HOSP PALLIAT NURS JI J. Hosp. Palliat. Nurs. PD MAY PY 2013 VL 15 IS 3 BP 171 EP 176 DI 10.1097/NJH.0b013e3182765a17 PG 6 WC Nursing SC Nursing GA 124QG UT WOS:000317479700006 PM 23853526 ER PT J AU Li, H Wu, Q Li, J Yang, PA Zhu, ZL Luo, B Hsu, HC Mountz, JD AF Li, Hao Wu, Qi Li, Jun Yang, PingAr Zhu, Zilu Luo, Bao Hsu, Hui-Chen Mountz, John D. TI Cutting Edge: Defective Follicular Exclusion of Apoptotic Antigens Due to Marginal Zone Macrophage Defects in Autoimmune BXD2 Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRECURSOR B-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; PATHOGENIC AUTOANTIBODIES; DENDRITIC CELLS; T-CELLS; TOLERANCE; INTERLEUKIN-17; RECEPTORS; TRANSPORT AB Marginal zone macrophages (MZMs) act as a barrier to entry of circulating apoptotic debris into the follicles of secondary lymphoid organs. In autoimmune BXD2 mice, there is a progressive reduction in the function and numbers of MZMs. Absence of MZMs results in retention of apoptotic cell (AC) debris within the marginal zone (MZ) and increased loading of AC Ags on MZ B cells and MZ-precursor (MZ-P) B cells. The MZ-P B cells are capable of translocating the AC Ags to the follicular zone and stimulating T cells. Both MZMs and MZ-P B cells from BXD2 mice express low levels of tolerogenic signals and high levels of inflammatory signals. Thus, the current study suggests a multifaceted mechanism in which MZMs maintain tolerance to apoptotic autoantigens and suppress their translocation to follicles. Lack of clearance of apoptotic debris by MZMs drives follicular Ag-transportation by MZ-P B cells to stimulate an autoimmune response. The Journal of Immunology, 2013, 190:4465-4469. C1 [Li, Hao; Wu, Qi; Li, Jun; Yang, PingAr; Luo, Bao; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Li, Hao; Mountz, John D.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Zhu, Zilu] Univ Alabama Birmingham, Dept Med, Div Hematol & Oncol, Birmingham, AL 35294 USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Hsu, HC (reprint author), Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Room 307,Shelby Bldg,1825 Univ Blvd, Birmingham, AL 35294 USA. EM rheu078@uab.edu; jdmountz@uab.edu RI Li, Hao/N-7406-2015; OI Li, Hao/0000-0002-2171-8826; Zhu, Zilu/0000-0002-1944-0108 FU VA Merit Review Grant [1I01BX000600-01]; National Institutes of Health/National Institute of Allergy and Infectious Disease [1AI 071110, ARRA 3RO1AI71110-02S1, 1RO1 AI083705]; American College of Rheumatology Research and Education Foundation; Arthritis Foundation; Lupus Research Institute FX This work was supported by a VA Merit Review Grant (1I01BX000600-01), as well as grants from the National Institutes of Health/National Institute of Allergy and Infectious Disease (1AI 071110, ARRA 3RO1AI71110-02S1, and 1RO1 AI083705), the American College of Rheumatology Research and Education Foundation, the Arthritis Foundation, and the Lupus Research Institute. Flow cytometry and confocal imaging were carried out at the University of Alabama at Birmingham Comprehensive Flow Cytometry Core (P30 AR048311 and P30 AI027767) and University of Alabama at Birmingham Analytic Imaging and Immunoreagents Core (P30 AR048311), respectively. NR 23 TC 9 Z9 9 U1 1 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 MAY 1 PY 2013 VL 190 IS 9 BP 4465 EP 4469 DI 10.4049/jimmunol.1300041 PG 5 WC Immunology SC Immunology GA 130IP UT WOS:000317907900008 PM 23543760 ER PT J AU Ioannou, GN Haigh, WG Thorning, D Savard, C AF Ioannou, George N. Haigh, W. Geoffrey Thorning, David Savard, Christopher TI Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis SO JOURNAL OF LIPID RESEARCH LA English DT Article DE Kupffer cells; foam cells; steatohepatitis; nonalcoholic steatohepatitis ID FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; DIETARY-CHOLESTEROL; ADIPOCYTE DEATH; ADIPOSE-TISSUE; UNITED-STATES; MICE; EZETIMIBE; OBESE; INFLAMMATION AB We sought to determine whether hepatic cholesterol crystals are present in patients or mice with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH), and whether their presence or distribution correlates with the presence of NASH as compared with simple steatosis. We identified, by filipin staining, free cholesterol within hepatocyte lipid droplets in patients with NASH and in C57BL/6J mice that developed NASH following a high-fat high-cholesterol diet. Under polarized light these lipid droplets exhibited strong birefringence suggesting that some of the cholesterol was present in the form of crystals. Activated Kupffer cells aggregated around dead hepatocytes that included strongly birefringent cholesterol crystals, forming "crown-like structures" similar to those recently described in inflamed visceral adipose tissue. These Kupffer cells appeared to process the lipid of dead hepatocytes turning it into activated lipid-laden "foam cells" with numerous small cholesterol-containing droplets. In contrast, hepatocyte lipid droplets in patients and mice with simple steatosis did not exhibit cholesterol crystals and their Kupffer cells did not form crown-like structures or transform into foam cells. Our results suggest that cholesterol crystallization within hepatocyte lipid droplets and aggregation and activation of Kupffer cells in crown-like structures around such droplets represent an important, novel mechanism for progression of simple steatosis to NASH.-Ioannou, G. N., W. G. Haigh, D. Thorning, and C. Savard. Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis. J. Lipid Res. 2013. 54: 1326-1334. C1 [Ioannou, George N.; Haigh, W. Geoffrey; Savard, Christopher] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. [Thorning, David] Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA. [Ioannou, George N.; Haigh, W. Geoffrey; Savard, Christopher] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. EM georgei@medicine.washington.edu FU Research Enhancement Award Program, Office of Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA FX This work was supported by a grant from the Research Enhancement Award Program (to G.N.I.), Office of Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA. The authors report no conflicts of interest. NR 29 TC 36 Z9 39 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2013 VL 54 IS 5 BP 1326 EP 1334 DI 10.1194/jlr.M034876 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 123MO UT WOS:000317394300018 PM 23417738 ER PT J AU Quiroz, YT Stern, CE Reiman, EM Brickhouse, M Ruiz, A Sperling, RA Lopera, F Dickerson, BC AF Quiroz, Yakeel T. Stern, Chantal E. Reiman, Eric M. Brickhouse, Michael Ruiz, Adriana Sperling, Reisa A. Lopera, Francisco Dickerson, Bradford C. TI Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID E280A PS-1 MUTATION; MILD AD DEMENTIA; HIPPOCAMPAL ATROPHY; NORMAL ADULTS; SERIAL MRI; SIGNATURE; THICKNESS; POPULATION; PREVENTION; PROPOSAL AB Background Sporadic late-onset Alzheimer's disease (AD) dementia has been associated with a 'signature' of cortical atrophy in paralimbic and heteromodal association regions measured with MRI. Objective To investigate whether a similar pattern of cortical atrophy is present in presymptomatic presenilin 1 E280A mutation carriers an average of 6 years before clinical symptom onset. Methods 40 cognitively normal volunteers from a Colombian population with familial AD were included; 18 were positive for the AD-associated presenilin 1 mutation (carriers, mean age=38) whereas 22 were non-carriers. T1-weighted volumetric MRI images were acquired and cortical thickness was measured. A priori regions of interest from our previous work were used to obtain thickness from AD-signature regions. Results Compared to non-carriers, presymptomatic presenilin 1 mutation carriers exhibited thinner cortex within the AD-signature summary measure (p<0.008). Analyses of individual regions demonstrated thinner angular gyrus, precuneus and superior parietal lobule in carriers compared to non-carriers, with trend-level effects in the medial temporal lobe. Conclusion Results demonstrate that cognitively normal individuals genetically determined to develop AD have a thinner cerebral cortex than non-carriers in regions known to be affected by typical late-onset sporadic AD. These findings provide further support for the hypothesis that cortical atrophy is present in preclinical AD more than 5 years prior to symptom onset. Further research is needed to determine whether this method could be used to characterise the age-dependent trajectory of cortical atrophy in presymptomatic stages of AD. C1 [Quiroz, Yakeel T.; Stern, Chantal E.] Boston Univ, Dept Psychol, Ctr Memory & Brain, Boston, MA 02215 USA. [Quiroz, Yakeel T.; Ruiz, Adriana; Lopera, Francisco] Univ Antioquia, Grp Neurociencias, Medellin, Colombia. [Stern, Chantal E.; Sperling, Reisa A.; Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Stern, Chantal E.; Brickhouse, Michael; Sperling, Reisa A.; Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Brickhouse, Michael; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Dementia Unit, Boston, MA 02114 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Sperling, Reisa A.; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Frontotemporal Dementia Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU Boston University Center for Neuroscience; Boston University Alzheimer's Disease Center pilot award [P30 AG13846]; COLCIENCIAS-Colombia [1115-343-19127]; National Institute of Neurological Disorders and Stroke [F31-NS078786-01A1]; National Institute on Aging [R01-AG029411, P50-AG005134]; Alzheimer's Association [IIRG-09-13356]; Department of Psychology FX This study was supported by the Boston University Center for Neuroscience (to CES), Department of Psychology (to CES and YTQ), a Boston University Alzheimer's Disease Center pilot award (P30 AG13846 to CES), and COLCIENCIAS-Colombia (Project: 1115-343-19127 to FL), the National Institute of Neurological Disorders and Stroke (F31-NS078786-01A1 to YTQ), the National Institute on Aging (R01-AG029411 and P50-AG005134 to BCD), and the Alzheimer's Association (IIRG-09-13356 to BCD). NR 40 TC 18 Z9 18 U1 0 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 2013 VL 84 IS 5 BP 556 EP 561 DI 10.1136/jnnp-2012-303299 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 123KR UT WOS:000317388800018 PM 23134660 ER PT J AU Maas, MB Kwolek, CJ Hirsch, JA Jaff, MR Rordorf, GA AF Maas, Matthew B. Kwolek, Christopher J. Hirsch, Joshua A. Jaff, Michael R. Rordorf, Guy A. TI Clinical risk predictors for cerebral hyperperfusion syndrome after carotid endarterectomy SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID STROKE AB Background Cerebral hyperperfusion syndrome (CHS) is an important complication of carotid endarterectomy (CEA), yet prior research has been limited to small cohorts and retrospective analyses, or studies using radiographic rather than clinical definitions. Methods A prospective monitoring system was implemented to monitor CEA outcomes at a major academic medical centre. Independent, trained monitors from the neurology department examined all patients undergoing CEA preoperatively and postoperatively at 24 h and 30 days. Clinical variables were analysed to identify risk factors for CHS, which was defined as cases with postoperative development of a severe headache, new neurological deficits without infarction, seizure or intracerebral haemorrhage. Results Between 2008 and 2010, 841 CEAs were monitored and CHS occurred in 14 (1.7%) subjects, including seizures in 5 (0.6%) and intracerebral haemorrhage in 4 (0.5%). Univariate analysis identified a history of dyslipidaemia, coronary artery disease, diastolic blood pressure, intraoperative shunt use and non-elective CEA (performed during hospitalisation for a symptomatic ipsilateral stroke, transient ischaemic attack or amaurosis fugax) as potential risks for CHS (all p <= 0.15); other variables-including the degree of ipsilateral and contralateral stenosis, operative time, intraoperative EEG slowing, history of prior CEA or carotid stent and time from prior carotid interventions-were not significant. Logistic regression confirmed the risk association between non-elective CEA and CHS (p=0.046). Conclusions Independent, prospective monitoring of a large cohort of CEA cases identified a brief time interval between ischaemic symptoms and endarterectomy as the clearest risk factor for CHS. C1 [Maas, Matthew B.] Northwestern Univ, Dept Neurol, Div Crit Care Neurol, Chicago, IL 60611 USA. [Maas, Matthew B.; Rordorf, Guy A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Div Vasc & Crit Care Neuro, Boston, MA 02115 USA. [Kwolek, Christopher J.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Intervent Neuroradiol, Boston, MA 02115 USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol,Sect Vasc Med, Boston, MA USA. RP Maas, MB (reprint author), Northwestern Univ, Dept Neurol, Div Crit Care Neurol, 710 N Lake Shore Dr,11th Floor, Chicago, IL 60611 USA. EM mbmaas@northwestern.edu NR 8 TC 10 Z9 10 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 2013 VL 84 IS 5 BP 569 EP 572 DI 10.1136/jnnp-2012-303659 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 123KR UT WOS:000317388800020 PM 23243262 ER PT J AU Guo, YA Chekaluk, Y Zhang, JM Du, JY Gray, NS Wu, CL Kwiatkowski, DJ AF Guo, Yanan Chekaluk, Yvonne Zhang, Jianming Du, Jinyan Gray, Nathanael S. Wu, Chin-Lee Kwiatkowski, David J. TI TSC1 involvement in bladder cancer: diverse effects andtherapeutic implications SO JOURNAL OF PATHOLOGY LA English DT Article DE TSC1; TSC2; bladder cancer; kinase inhibitor; Torin1 ID SCLEROSIS GENE TSC1; TYROSINE KINASE; ANTITUMOR-ACTIVITY; MTOR; MUTATIONS; INHIBITOR; COMPLEX; PHOSPHORYLATION; ACTIVATION; NEOPLASMS AB TSC1 is often mutated in bladder cancer. However the importance of this event in disease pathogenesis and its implications for therapy are uncertain. We used genomic sequencing to examine the involvement of TSC1 in bladder cancer, and signalling pathway analysis and small-molecule screening to identify targeted therapeutic strategies in TSC1 mutant bladder cancer cell lines. TSC1 loss of heterozygosity was seen in 54% of bladder cancers. Two (4.9%) of these 41 bladder cancers had TSC1 mutations by exon-based sequencing. Analysis of 27 bladder cancer cell lines demonstrated inactivating TSC1 mutations in three: RT-4, HCV29, 971. Interestingly, only RT-4 showed classic feedback inhibition of AKT, and was highly sensitive to treatment with mTOR inhibitors rapamycin and Torin1. 971 cells showed constitutive EGFR activation, and were highly sensitive to combined treatment with the mTOR inhibitor Torin1 and EGFR inhibitors Lapatinib or Afatinib. A BRAF missense mutation G469V was found in HCV29 cells, and AKT activation was dependent on BRAF, but independent of ERK. A kinase inhibitor screen of HCV29 cells showed strong growth inhibition by the Hsp90 inhibitor NVP-AUY922, and we then found synergistic inhibitory effects of NVP-AUY922 combined with either Torin1 or rapamycin on cell survival for both HCV29 and 971 cells. In aggregate, these findings indicate that there are highly variable mutation profiles and signalling pathway activation in TSC1-mutant bladder cancer. Furthermore, combined Hsp90/mTOR inhibition is a promising therapeutic approach for TSC1 mutant bladder cancer. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Guo, Yanan; Chekaluk, Yvonne; Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, Div Translat Med, Boston, MA 02115 USA. [Guo, Yanan; Chekaluk, Yvonne; Kwiatkowski, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Jianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Du, Jinyan] Broad Inst Harvard Univ & Massachusetts Inst Tech, Cambridge, MA USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, Dept Med, Div Translat Med, 75 Francis St, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu FU National Institutes of Health [1P01CA120964] FX We thank Dr Pasi A Janne and Krishna M Vasudevan (Dana Farber Cancer Institute, MA, USA) for kindly providing inhibitors used in this study; Margaret A Knowles (St James's University Hospital, UK) for kindly providing the HCV29 and 97-1 bladder cancer cell lines; and Laura McConnail for assistance with the Oncomap screen. This study was supported by the National Institutes of Health (Grant No. 1P01CA120964). NR 39 TC 23 Z9 24 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAY PY 2013 VL 230 IS 1 BP 17 EP 27 DI 10.1002/path.4176 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 124AE UT WOS:000317434000004 PM 23401075 ER PT J AU Golden-Mason, L McMahan, RH Strong, M Reisdorph, R Mahaffey, S Palmer, BE Cheng, LL Kulesza, C Hirashima, M Niki, T Rosen, HR AF Golden-Mason, Lucy McMahan, Rachel H. Strong, Michael Reisdorph, Richard Mahaffey, Spencer Palmer, Brent E. Cheng, Linling Kulesza, Caroline Hirashima, Mitsuomi Niki, Toshiro Rosen, Hugo R. TI Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice SO JOURNAL OF VIROLOGY LA English DT Article ID NASOPHARYNGEAL CARCINOMA-CELLS; C VIRUS-INFECTION; NK CELLS; T-CELLS; ADAPTIVE IMMUNITY; VIRAL-INFECTIONS; LIGAND-BINDING; TIM-3; INNATE; RECEPTOR AB Galectin-9 is a pleiotropic immune modulator affecting numerous cell types of innate and adaptive immunity. Patients with chronic infection with either hepatitis C virus (HCV) or HIV have elevated circulating levels. Limited data exist on the regulation of natural killer (NK) cell function through interaction with galectin-9. We found that galectin-9 ligation downregulates multiple immune-activating genes, including eight involved in the NK cell-mediated cytotoxicity pathway, impairs lymphokine-activated killing, and decreases the proportion of gamma interferon (IFN-gamma)-producing NK cells that had been stimulated with interleukin-12 (IL-12)/IL-15. We demonstrate that the transcriptional and functional changes induced by galectin-9 are independent of Tim-3. Consistent with these results for humans, we find that the genetic absence of galectin-9 in mice is associated with greater IFN-gamma production by NK cells and enhanced degranulation. We also show that in the setting of a short-term (4-day) murine cytomegalovirus infection, terminally differentiated NKs accumulate in the livers of galectin-9 knockout mice, and that hepatic NKs spontaneously produce significantly more IFN-gamma in this setting. Taken together, our results indicate that galectin-9 engagement impairs the function of NK cells, including cytotoxicity and cytokine production. C1 [Golden-Mason, Lucy; McMahan, Rachel H.; Cheng, Linling; Rosen, Hugo R.] UCD, Dept Med, Hepatitis C Ctr, Div Gastroenterol & Hepatol, Aurora, CO USA. [Golden-Mason, Lucy; Reisdorph, Richard; Mahaffey, Spencer; Rosen, Hugo R.] UCD, Integrated Program Immunol, Denver, CO USA. [Golden-Mason, Lucy; Reisdorph, Richard; Mahaffey, Spencer; Rosen, Hugo R.] NJH, Denver, CO USA. [Golden-Mason, Lucy; McMahan, Rachel H.; Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. [Strong, Michael] NJH, Ctr Genes Environm & Hlth, Denver, CO USA. [Reisdorph, Richard] NJH, Dept Pediat, Denver, CO USA. [Palmer, Brent E.] UCD, Div Allergy & Clin Immunol, Aurora, CO USA. [Kulesza, Caroline] UCD, Dept Microbiol, Aurora, CO USA. [Hirashima, Mitsuomi; Niki, Toshiro] Kagawa Univ, Fac Med, Dept Immmunol & Immunopathol, Kagawa, Japan. RP Rosen, HR (reprint author), UCD, Dept Med, Hepatitis C Ctr, Div Gastroenterol & Hepatol, Aurora, CO USA. EM hugo.rosen@ucdenver.edu FU VA [R21AIO76161, R21AIO76161-01A2S1]; [U19 AI 1066328]; [K24AI083742] FX This work was supported by U19 AI 1066328 (H.R.R.), K24AI083742 (H.R.R.), a VA Merit Review grant (H.R.R.), R21AIO76161 (B.E.P.), and R21AIO76161-01A2S1 (B.E.P.). NR 50 TC 21 Z9 25 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2013 VL 87 IS 9 BP 4835 EP 4845 DI 10.1128/JVI.01085-12 PG 11 WC Virology SC Virology GA 123UK UT WOS:000317416400006 PM 23408620 ER PT J AU Buttenheim, AM Asch, DA AF Buttenheim, Alison M. Asch, David A. TI Behavioral Economics: The Key to Closing the Gap on Maternal, Newborn and Child Survival for Millennium Development Goals 4 and 5? SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Behavior change; Behavioral economics; Maternal and child health; Millennium development goals ID FINANCIAL INCENTIVES; CONTROLLED-TRIAL; HEALTH BEHAVIOR; VOUCHER SCHEME; BANGLADESH; DECISIONS; COVERAGE; MODEL AB Millennium Development Goals (MDGs) 4 and 5 set ambitious targets to reduce maternal, newborn and child mortality by 2015. With 2015 fast approaching, there has been a concerted effort in the global health community to "close the gap" on the MDG targets. Recent consensus initiatives and frameworks have refocused attention on evidence-based, low-cost interventions that can reduce mortality and morbidity, and have argued for additional funding to increase access to and coverage of these life-saving interventions. However, funding alone will not close the gap on MDGs 4 and 5. Even when high-quality, affordable products and services are readily available, uptake is often low. Progress will therefore require not just money, but also advances in health-related behavior change and decision-making. Behavioral economics offers one way to achieve real progress by improving our understanding of how individuals make choices under information and time constraints, and by offering new approaches to make it easier for individuals to do what is in their best interest and harder to do what is not. We introduce five behavioral economic principles and demonstrate how they could boost efforts to improve maternal, newborn, and child health in pursuit of MDGs 4 and 5. C1 [Buttenheim, Alison M.] Univ Penn, Sch Nursing, Dept Family & Community Hlth, Philadelphia, PA 19104 USA. [Buttenheim, Alison M.] Univ Penn, LDI Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Buttenheim, AM (reprint author), Univ Penn, Sch Nursing, Dept Family & Community Hlth, Fagin 235L,418 Curie Blvd, Philadelphia, PA 19104 USA. EM abutt@nursing.upenn.edu OI Asch, David/0000-0002-7970-286X NR 30 TC 2 Z9 2 U1 0 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD MAY PY 2013 VL 17 IS 4 BP 581 EP 585 DI 10.1007/s10995-012-1042-7 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 126IS UT WOS:000317608200002 PM 22618489 ER PT J AU Weissman, JS Vogeli, C Levy, DE AF Weissman, Joel S. Vogeli, Christine Levy, Douglas E. TI The Quality of Hospital Care for Medicaid and Private Pay Patients SO MEDICAL CARE LA English DT Article DE quality of care; medicaid; hospitals; access to care ID OF-CARE; OUTCOMES; PROGRAM; STATE AB Context: Understanding Medicaid performance relative to private payers and among other states may lead to better value. Design, Setting, and Participants: Hospital Quality Alliance data from 2007-2008 were used to create composite "all-or-none" quality scores for nearly 900,000 nonelderly adult patients hospitalized with acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia. Main Outcome Measures: Differences in the quality of care received by Medicaid compared with privately insured patients at the national and state levels. Results: Nationally, 88% of Medicaid beneficiaries received all appropriate processes of care when hospitalized for AMI, compared with 73% for CHF and 77% for pneumonia. Private patients received higher quality of care than Medicaid patients, but differences were small (1.3 percentage point difference, pneumonia; 2.7, AMI; 2.9, CHF; all P < 0.05). At the state level, the differences averaged <3 percentage points across all conditions, but some states (2-8 states depending on the condition) exhibited significant (P < 0.05) differences of >5 percentage points in favor of private patients. Two states exhibited significantly better quality of care for their Medicaid patients in excess of 5 percentage points. Quality scores for both Medicaid and private patients varied significantly by state but were highly correlated (correlations for AMI = 0.80, CHF = 0.84, pneumonia = 0.80; all P < 0.001). Conclusions: Small national differences in quality between hospitalized Medicaid and private patients are promising, although merit close monitoring as states are forced to curb Medicaid reimbursements. Although quality for Medicaid patients varied by state, high correlations with private patients suggest that the factors driving quality have more to do with geographic factors in the delivery of hospital services than with state-established Medicaid policies. C1 [Weissman, Joel S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Weissman, Joel S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Weissman, Joel S.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Vogeli, Christine; Levy, Douglas E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Vogeli, Christine; Levy, Douglas E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Weissman, JS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,Ctr Surg & Publ Hlth, Boston, MA 02115 USA. EM jweissman@partners.org FU Kaiser Family Foundation's Commission FX Supported by the Kaiser Family Foundation's Commission on Medicaid and the Uninsured. NR 24 TC 7 Z9 8 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2013 VL 51 IS 5 BP 389 EP 395 DI 10.1097/MLR.0b013e31827fef95 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 126WU UT WOS:000317653900004 PM 23358385 ER PT J AU Voils, CI Maciejewski, ML Hoyle, RH Reeve, BB Gallagher, MP Bryson, CL Yancy, WS AF Voils, Corrine I. Maciejewski, Matthew L. Hoyle, Rick H. Reeve, Bryce B. Gallagher, Matthew P. Bryson, Christopher L. Yancy, William S., Jr. TI Behavioral Science and Reasons for Nonadherence to Medication Response SO MEDICAL CARE LA English DT Letter C1 [Voils, Corrine I.; Maciejewski, Matthew L.; Gallagher, Matthew P.; Yancy, William S., Jr.] Duke Univ, Med Ctr, Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27706 USA. [Voils, Corrine I.; Maciejewski, Matthew L.; Yancy, William S., Jr.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA. [Hoyle, Rick H.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27706 USA. [Reeve, Bryce B.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Bryson, Christopher L.] Univ Washington, Vet Affairs Puget Sound, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98195 USA. [Bryson, Christopher L.] Univ Washington, Dept Med, Seattle, WA USA. RP Voils, CI (reprint author), Duke Univ, Med Ctr, Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27706 USA. FU NIA NIH HHS [R21 AG035233] NR 3 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2013 VL 51 IS 5 BP 468 EP 469 DI 10.1097/MLR.0b013e31828fadbf PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 126WU UT WOS:000317653900016 PM 23552432 ER PT J AU Baptista, AP Olivier, BJ Goverse, G Greuter, M Knippenberg, M Kusser, K Domingues, RG Veiga-Fernandes, H Luster, AD Lugering, A Randall, TD Cupedo, T Mebius, RE AF Baptista, A. P. Olivier, B. J. Goverse, G. Greuter, M. Knippenberg, M. Kusser, K. Domingues, R. G. Veiga-Fernandes, H. Luster, A. D. Lugering, A. Randall, T. D. Cupedo, T. Mebius, R. E. TI Colonic patch and colonic SILT development are independent and differentially regulated events SO MUCOSAL IMMUNOLOGY LA English DT Article ID LYMPHOTOXIN-BETA-RECEPTOR; ISOLATED LYMPHOID FOLLICLES; TISSUE INDUCER CELLS; INTESTINAL-MUCOSA; DENDRITIC CELLS; PEYERS-PATCHES; DEFICIENT MICE; B-LYMPHOCYTES; ALPHA-BETA; T-CELLS AB Intestinal lymphoid tissues have to simultaneously ensure protection against pathogens and tolerance toward commensals. Despite such vital functions, their development in the colon is poorly understood. Here, we show that the two distinct lymphoid tissues of the colon-colonic patches and colonic solitary intestinal lymphoid tissues (SILTs)-can easily be distinguished based on anatomical location, developmental timeframe, and cellular organization. Furthermore, whereas colonic patch development depended on CXCL13-mediated lymphoid tissue inducer (LTi) cell clustering followed by LT alpha-mediated consolidation, early LTi clustering at SILT anlagen did not require CXCL13, CCR6, or CXCR3. Subsequent dendritic cell recruitment to and gp38(+)VCAM-1(+) lymphoid stromal cell differentiation within SILTs required LT alpha; B-cell recruitment and follicular dendritic cell differentiation depended on MyD88-mediated signaling, but not the microflora. In conclusion, our data demonstrate that different mechanisms, mediated mainly by programmed stimuli, induce the formation of distinct colonic lymphoid tissues, therefore suggesting that these tissues may have different functions. C1 [Baptista, A. P.; Olivier, B. J.; Goverse, G.; Greuter, M.; Knippenberg, M.; Mebius, R. E.] Vrije Univ Amsterdam Med Ctr, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands. [Baptista, A. P.] Univ Porto, GABBA PhD Program, P-4100 Oporto, Portugal. [Kusser, K.; Randall, T. D.] Univ Rochester, Dept Med, Div Rheumatol Allergy & Immunol, Rochester, NY USA. [Domingues, R. G.; Veiga-Fernandes, H.] Fac Med Lisbon, Inst Mol Med, Lisbon, Portugal. [Luster, A. D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Charlestown, MA USA. [Lugering, A.] Univ Munster, Dept Med B, D-48149 Munster, Germany. [Cupedo, T.] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. RP Mebius, RE (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands. EM r.mebius@vumc.nl OI Veiga-Fernandes, Henrique/0000-0001-6216-1836 FU Fundacao para a Ciencia e Tecnologia - Portugal [SFRH/BD/33247/2007]; Dutch Digestive Disease Foundation; US National Institutes of Health [R01CA069212, AI061511, AI072689, HL069409]; Netherlands Organization for Scientific Research [917.10.377]; VICI [918.56.612] FX We thank B. Beuger, D. Schut, and E. Keuning for animal care; and D. Littman, P. Leenen, and S. Nighikawa for antibodies. This work was supported by grants from Fundacao para a Ciencia e Tecnologia - Portugal (SFRH/BD/33247/2007 to APB), Dutch Digestive Disease Foundation (to MK), US National Institutes of Health (R01CA069212 to ADL; and AI061511, AI072689, and HL069409 to TDR), and Netherlands Organization for Scientific Research (VIDI grant 917.10.377 to TC; and VICI grant 918.56.612 to REM). NR 39 TC 16 Z9 16 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAY PY 2013 VL 6 IS 3 BP 511 EP 521 DI 10.1038/mi.2012.90 PG 11 WC Immunology SC Immunology GA 127TX UT WOS:000317722800008 PM 22990625 ER PT J AU Albacker, LA Yu, S Bedoret, D Lee, WL Umetsu, SE Monahan, S Freeman, GJ Umetsu, DT DeKruyff, RH AF Albacker, L. A. Yu, S. Bedoret, D. Lee, W-L Umetsu, S. E. Monahan, S. Freeman, G. J. Umetsu, D. T. DeKruyff, R. H. TI TIM-4, expressed by medullary macrophages, regulates respiratory tolerance by mediating phagocytosis of antigen-specific T cells SO MUCOSAL IMMUNOLOGY LA English DT Article ID AIRWAY HYPERREACTIVITY; DENDRITIC CELLS; ADAPTIVE IMMUNITY; APOPTOTIC CELLS; PHOSPHATIDYLSERINE; IDENTIFICATION; EXPOSURE; CLEARANCE; INFLUENZA; RESPONSES AB Respiratory exposure to antigen induces T cell tolerance via several overlapping mechanisms that limit the immune response. While the mechanisms involved in the development of Treg cells have received much attention, those that result in T cell deletion are largely unknown. Herein, we show that F4/80(+) lymph node medullary macrophages expressing TIM-4, a phosphatidylserine receptor, remove antigen-specific T cells during respiratory tolerance, thereby reducing secondary T cell responses. Blockade of TIM-4 inhibited the phagocytosis of antigen-specific T cells by TIM-4 expressing lymph node medullary macrophages, resulting in an increase in the number of antigen-specific T cells and the abrogation of respiratory tolerance. Moreover, specific depletion of medullary macrophages inhibited the induction of respiratory tolerance, highlighting the key role of TIM-4 and medullary macrophages in tolerance. Therefore, TIM-4-mediated clearance of antigen specific T cells represents an important previously unrecognized mechanism regulating respiratory tolerance. C1 [Albacker, L. A.; Yu, S.; Bedoret, D.; Lee, W-L; Umetsu, S. E.; Monahan, S.; Umetsu, D. T.; DeKruyff, R. H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Boston, MA 02115 USA. [Albacker, L. A.; Yu, S.; Bedoret, D.; Lee, W-L; Umetsu, S. E.; Monahan, S.; Umetsu, D. T.; DeKruyff, R. H.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Freeman, G. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Med Oncol, Boston, MA 02115 USA. RP DeKruyff, RH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Boston, MA 02115 USA. EM rosemarie.dekruyff@childrens.harvard.edu FU Program on Immunology, Division of Medical Sciences, Harvard University; [NIH P01 AI054456]; [NIH RO1 089955] FX We thank Jessica Walters and the Harvard Digestive Diseases Center Imaging Core for expert help and Elena Tonti of the von Andrian lab for training in the removal and orientation of lymph nodes for confocal microscopy. This work was supported by NIH P01 AI054456 (to D.T.U., G.J.F., R.D.K.,), NIH RO1 089955 (to G.F., R.D.K.), and the Program on Immunology, Division of Medical Sciences, Harvard University (to L.A.A.). NR 27 TC 15 Z9 16 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAY PY 2013 VL 6 IS 3 BP 580 EP 590 DI 10.1038/mi.2012.100 PG 11 WC Immunology SC Immunology GA 127TX UT WOS:000317722800014 PM 23149665 ER PT J AU Chen, BB Coon, TA Glasser, JR McVerry, BJ Zhao, J Zhao, YT Zou, CB Ellis, B Sciurba, FC Zhang, YZ Mallampalli, RK AF Chen, Bill B. Coon, Tiffany A. Glasser, Jennifer R. McVerry, Bryan J. Zhao, Jing Zhao, Yutong Zou, Chunbin Ellis, Bryon Sciurba, Frank C. Zhang, Yingze Mallampalli, Rama K. TI A combinatorial F box protein directed pathway controls TRAF adaptor stability to regulate inflammation SO NATURE IMMUNOLOGY LA English DT Article ID RECEPTOR-ASSOCIATED FACTOR-3; SCF UBIQUITIN LIGASE; FAMILY; DEGRADATION; ACTIVATION; SEPSIS; IDENTIFICATION; SUBUNIT; FBXL2 AB Uncontrolled activation of tumor necrosis factor receptor-associated factor (TRAF) proteins may result in profound tissue injury by linking surface signals to cytokine release. Here we show that a ubiquitin E3 ligase component, Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by destabilizing a sentinel TRAF inhibitor, Fbxl2. Fbxo3 and TRAF protein in circulation positively correlated with cytokine responses in subjects with sepsis, and we identified a polymorphism in human Fbxo3, with one variant being hypofunctional. A small-molecule inhibitor targeting Fbxo3 was sufficient to lessen severity of cytokine-driven inflammation in several mouse disease models. These studies identified a pathway of innate immunity that may be useful to detect subjects with altered immune responses during critical illness or provide a basis for therapeutic intervention targeting TRAF protein abundance. C1 [Chen, Bill B.; Coon, Tiffany A.; Glasser, Jennifer R.; McVerry, Bryan J.; Zhao, Jing; Zhao, Yutong; Zou, Chunbin; Ellis, Bryon; Sciurba, Frank C.; Zhang, Yingze; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. EM chenb@upmc.edu; mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; Merit Review Award from the US Department of Veterans Affairs; National Institutes [HL096376, HL097376, HL081784, HL068135, HL098174, HL116472, HL01916, P50HL084948]; American Heart Association [12SDG9050005, 12SDG12040330, 12GRNT11820019] FX We thank A. Lagneaux and S. Barge for assistance with studies. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376, HL081784, HL068135 and HL098174 (to R. K. M.), HL116472 (to B. B. C.), HL01916 (to Y.Z.) and P50HL084948 (F. C. S.), American Heart Association awards 12SDG9050005 (to J.Z.) and 12SDG12040330 (to C.Z.), and American Heart Association Grant-in-Aid 12GRNT11820019 (B.J.M.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 43 TC 46 Z9 48 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2013 VL 14 IS 5 BP 470 EP + DI 10.1038/ni.2565 PG 11 WC Immunology SC Immunology GA 127XL UT WOS:000317732100012 PM 23542741 ER PT J AU Lupfer, C Thomas, PG Anand, PK Vogel, P Milasta, S Martinez, J Huang, GH Green, M Kundu, M Chi, HB Xavier, RJ Green, DR Lamkanfi, M Dinarello, CA Doherty, PC Kanneganti, TD AF Lupfer, Christopher Thomas, Paul G. Anand, Paras K. Vogel, Peter Milasta, Sandra Martinez, Jennifer Huang, Gonghua Green, Maggie Kundu, Mondira Chi, Hongbo Xavier, Ramnik J. Green, Douglas R. Lamkanfi, Mohamed Dinarello, Charles A. Doherty, Peter C. Kanneganti, Thirumala-Devi TI Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection SO NATURE IMMUNOLOGY LA English DT Article ID 1918 INFLUENZA-VIRUS; IFN-GAMMA PRODUCTION; DOUBLE-STRANDED-RNA; CD8(+) T-CELLS; LISTERIA-MONOCYTOGENES; IL-1-BETA PRODUCTION; IMMUNE-RESPONSE; DENDRITIC CELLS; AUTOPHAGY; INNATE AB NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-kappa B and MAP kinase signaling during bacterial infections, but the role of this immune axis during viral infections has not been addressed. We demonstrate that Nod2(-/-) and Ripk2(-/-) mice are hypersusceptible to infection with influenza A virus. Ripk2(-/-) cells exhibited defective autophagy of mitochondria (mitophagy), leading to enhanced mitochondrial production of superoxide and accumulation of damaged mitochondria, which resulted in greater activation of the NLRP3 inflammasome and production of IL-18. RIPK2 regulated mitophagy in a kinase-dependent manner by phosphorylating the mitophagy inducer ULK1. Accordingly, Ulk1(-/-) cells exhibited enhanced mitochondrial production of superoxide and activation of caspase-1. These results demonstrate a role for NOD2-RIPK2 signaling in protection against virally triggered immunopathology by negatively regulating activation of the NLRP3 inflammasome and production of IL-18 via ULK1-dependent mitophagy. C1 [Lupfer, Christopher; Thomas, Paul G.; Anand, Paras K.; Milasta, Sandra; Martinez, Jennifer; Huang, Gonghua; Green, Maggie; Chi, Hongbo; Green, Douglas R.; Doherty, Peter C.; Kanneganti, Thirumala-Devi] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA. [Vogel, Peter] St Jude Childrens Res Hosp, Vet Pathol Core, Memphis, TN 38105 USA. [Kundu, Mondira] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Lamkanfi, Mohamed] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium. [Lamkanfi, Mohamed] Univ Ghent VIB, Dept Med Prot Res, B-9052 Ghent, Belgium. [Dinarello, Charles A.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Doherty, Peter C.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. RP Kanneganti, TD (reprint author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM thirumala-devi.kanneganti@stjude.org RI Doherty, Peter Charles/C-4185-2013; OI Doherty, Peter Charles/0000-0002-5028-3489; Anand, Paras/0000-0003-2503-3653; Kanneganti, Thirumala-Devi/0000-0002-6395-6443; Thomas, Paul G./0000-0001-7955-0256 FU EU Framework Program 7 [256432]; European Research Council [281600]; Fund for Scientific Research Flanders [G030212N, 1.2.201.10.N.00, 1.5.122.11.N.00]; US National Institutes of Health [AR056296, AI101935, CA163507]; American Lebanese Syrian Associated Charities FX We thank members of the Veterinary Pathology Core lab at St. Jude for their work in processing of hematoxylin and eosin-stained and immunohistochemistry slides, members of the Cell and Tissue Imaging Core facility for their help in preparing and imaging transmission electron microscopy samples, and A. Coyle, E. Grant, J. Bertin (Millennium Pharmaceuticals), T. Mak (University of Toronto) and R. Flavell (Yale University) for providing mutant mice. M. L. is supported by grants from the EU Framework Program 7 (Marie-Curie grant 256432), European Research Council (grant 281600) and the Fund for Scientific Research Flanders (G030212N, 1.2.201.10.N.00 and 1.5.122.11.N.00). This work was supported by US National Institutes of Health grants (AR056296, AI101935 and CA163507) and the American Lebanese Syrian Associated Charities to T.-D.K. NR 49 TC 96 Z9 100 U1 2 U2 50 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2013 VL 14 IS 5 BP 480 EP + DI 10.1038/ni.2563 PG 11 WC Immunology SC Immunology GA 127XL UT WOS:000317732100013 PM 23525089 ER PT J AU Jang, JW Parambi, RJ McBride, SM Goldsmith, TA Holman, AS Chan, AW AF Jang, Joanne W. Parambi, Ron J. McBride, Sean M. Goldsmith, Tessa A. Holman, Allison S. Chan, Annie W. TI Clinical factors predicting for prolonged enteral supplementation in patients with oropharyngeal cancer treated with chemoradiation SO ORAL ONCOLOGY LA English DT Article DE Gastrostomy tube; G-tube; Oropharyngeal cancer; Chemoradiation; Squamous cell cancer of the head and neck; Enteral feeding ID PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; QUALITY-OF-LIFE; INTENSITY-MODULATED RADIOTHERAPY; LOCALLY ADVANCED HEAD; LONG-TERM DYSPHAGIA; BODY-MASS INDEX; NECK-CANCER; DEFINITIVE RADIOTHERAPY; RADIATION-THERAPY; PHASE-II AB Objectives: The purpose of this study is to determine the pre-treatment clinical factors associated with prolonged enteral feeding in patients with oropharyngeal cancer treated with chemoradiation. Materials and methods: One hundred and nine patients with stage III-IVB oropharyngeal carcinoma treated with definitive chemoradiation were analyzed. Feeding tube usage was defined as the duration of active usage for nutritional purposes. Results: Median follow-up was 4.4 years and median feeding tube usage was 2.5 months. On multivariate analysis, increasing duration of feeding tube usage was associated with narcotic use before treatment (p = 0.04), living alone at the time of treatment (p = 0.04), and larger pre-treatment decrease in body-mass index (p = 0.01). Prolonged feeding tube usage was associated with decreased overall survival (p = 0.06) and disease-free survival (p = 0.02) in univariate analysis. Conclusions: By identifying patients at risk for prolonged feeding tube usage, aggressive measures can be attempted to prevent feeding tube dependence. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Jang, Joanne W.; Parambi, Ron J.; McBride, Sean M.; Chan, Annie W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Jang, Joanne W.; McBride, Sean M.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Goldsmith, Tessa A.; Holman, Allison S.] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. RP Jang, JW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Lunder LL3, Boston, MA 02114 USA. EM jwjang@partners.org NR 32 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD MAY PY 2013 VL 49 IS 5 BP 438 EP 442 DI 10.1016/j.oraloncology.2012.12.003 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 121SU UT WOS:000317265300009 PM 23357527 ER PT J AU Kunz, PL Reidy-Lagunes, D Anthony, LB Bertino, EM Brendtro, K Chan, JA Chen, H Jensen, RT Kim, MK Klimstra, DS Kulke, MH Liu, EH Metz, DC Phan, AT Sippel, RS Strosberg, JR Yao, JC AF Kunz, Pamela L. Reidy-Lagunes, Diane Anthony, Lowell B. Bertino, Erin M. Brendtro, Kari Chan, Jennifer A. Chen, Herbert Jensen, Robert T. Kim, Michelle Kang Klimstra, David S. Kulke, Matthew H. Liu, Eric H. Metz, David C. Phan, Alexandria T. Sippel, Rebecca S. Strosberg, Jonathan R. Yao, James C. TI Consensus Guidelines for the Management and Treatment of Neuroendocrine Tumors SO PANCREAS LA English DT Article DE neuroendocrine tumors; carcinoid; neuroendocrine/diagnosis; neuroendocrine/treatment; neuroendocrine/pathology; pheochromocytoma ID HEPATIC METASTASES; DIAGNOSIS; SURVIVAL; EVEROLIMUS; CARCINOMAS AB Neuroendocrine tumors are a heterogeneous group of tumors originating in various anatomic locations. The management of this disease poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The recent completion of several phase 3 trials, including those evaluating octreotide, sunitinib, and everolimus, demonstrate that rigorous evaluation of novel agents in this disease is possible and can lead to practice-changing outcomes. Nevertheless, there are many aspects to the treatment of neuroendocrine tumors that remain unclear and controversial. The North American Neuroendocrine Tumor Society published a set of consensus guidelines in 2010, which provided an overview for the treatment of patients with these malignancies. Here, we present a set of consensus tables intended to complement these guidelines and serve as a quick, accessible reference for the practicing physician. C1 [Kunz, Pamela L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Reidy-Lagunes, Diane] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Anthony, Lowell B.] Univ Kentucky, Med Ctr, Dept Med, Lexington, KY 40536 USA. [Bertino, Erin M.] Ohio State Med Ctr, Dept Med, Columbus, OH USA. [Brendtro, Kari] NANETS & NET Patient Advocate, Vancouver, WA USA. [Chan, Jennifer A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Herbert; Sippel, Rebecca S.] Univ Wisconsin, Dept Surg, Madison, WI USA. [Jensen, Robert T.] NIDDK, Digest Dis Branch, Bethesda, MD USA. [Kim, Michelle Kang] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Liu, Eric H.] Vanderbilt Univ, Dept Surg, Nashville, TN 37240 USA. [Metz, David C.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Phan, Alexandria T.; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. [Strosberg, Jonathan R.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Med, Tampa, FL 33682 USA. RP Kunz, PL (reprint author), Stanford Univ, Sch Med, Dept Med, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM pkunz@stanford.edu FU Genentech; Merck; Sanofi; Novartis; Onyx/Bayer; Ipsen FX Pamela L. Kunz receives grant funding from Genentech, Merck, and Sanofi, is a consultant for OncoMed and Guardant Health, and has stock options from Guardant Health. Diane Reidy-Lagunes receives grant funding from Novartis and Merck, is a consultant for Novartis and Pfizer, and receives honorarium from Novartis. Jennifer A. Chan receives grant funding from Novartis, Onyx/Bayer, and Merck and has stock options from Merck. Eric H. Liu is a consultant for Novartis. Lowell B. Anthony receives grant funding from Novartis. David C. Metz is a consultant for Novartis and receives grant funding from Ipsen. Alexandria T. Phan is a consultant for Ipsen. Jonathan R. Strosberg is a consultant for Novartis and Pfizer, receives grant funding from Genentech and Novartis, and receives honorarium from Genentech, Pfizer and Sanofi. Matthew H. Kulke is a consultant for Novartis, Ipsen, Pfizer, and Lexicon and receives grant funding from Novartis. James C. Yao serves as a consultant for Novartis, Ipsen, and Pfizer and receives grant funding from Novartis. The remaining authors declare no conflicts of interest. NR 22 TC 87 Z9 91 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2013 VL 42 IS 4 BP 557 EP 577 DI 10.1097/MPA.0b013e31828e34a4 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126XF UT WOS:000317655200002 PM 23591432 ER PT J AU Park, CH Lee, IS Grippo, P Pandol, SJ Gukovskaya, AS Edderkaoui, M AF Park, Chang-Hwan Lee, In-Seok Grippo, Paul Pandol, Stephen J. Gukovskaya, Anna S. Edderkaoui, Mouad TI Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells SO PANCREAS LA English DT Article DE pancreatic cancer; smoking; apoptosis; autophagy ID TOBACCO-SPECIFIC CARCINOGEN; CANCER CELLS; CIGARETTE-SMOKE; PROTEIN-KINASE; EPITHELIAL-CELLS; NADPH OXIDASE; AUTOPHAGY; GROWTH; EXPRESSION; RECEPTORS AB Objectives: Cigarette smoking is a major risk factor for pancreatic cancer (PaCa). However, the mechanisms of smoking-induced PaCa remain unknown. Here we investigated the effect of smoking compounds on cell death pathways in pancreatic ductal cells, precursors of PaCa. Methods: Human pancreatic ductal cells (HPDE6-c7) were cultured with cigarette smoke extract (CSE) or smoking compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Apoptosis and autophagy were assessed by DNA fragmentation and immunofluorescence, respectively. Results: Exposure to CSE or NNK decreased DNA fragmentation and up-regulated Bcl(XL). Akt kinase was activated by smoking compounds through reactive oxygen species-dependent mechanism. Specifically, Akt activation was prevented by inhibition of nicotinamide adenine dinucleotide oxidase. Molecular or pharmacologic inhibitions of Akt prevented the antiapoptotic effect of smoking compounds. Smoking compounds stimulated rapid (1 hour) and transient activation of 5'-adenosine monophosphate-activated protein kinase and formation of autophagic vacuoles, indicating stimulation of autophagy. Repeated exposure to CSE/NNK (48 hours or longer) abolished the early activation of autophagic markers. Inhibition of Akt prevented the antiautophagic effect of long exposure to smoking compounds, indicating that smoking-induced late activation of Akt prevents autophagy. Conclusions: Long exposure of pancreatic ductal cells to smoking compounds inhibited apoptosis and autophagy. The results revealed a central role for Akt kinase in mediating key procarcinogenic effects of smoking compounds. C1 [Park, Chang-Hwan; Lee, In-Seok; Pandol, Stephen J.; Gukovskaya, Anna S.; Edderkaoui, Mouad] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Park, Chang-Hwan; Lee, In-Seok; Pandol, Stephen J.; Gukovskaya, Anna S.; Edderkaoui, Mouad] Univ Calif Los Angeles, Los Angeles, CA USA. [Park, Chang-Hwan] Chonnam Natl Univ, Sch Med, Div Gastroenterol, Dept Internal Med, Kwangju, South Korea. [Lee, In-Seok] Catholic Univ Korea, Div Gastroenterol, Dept Internal Med, Seoul, South Korea. [Grippo, Paul] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. RP Edderkaoui, M (reprint author), Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM medderkaoui@mednet.ucla.edu FU National Institute on Alcohol Abuse and Alcoholism [K01 AA019996]; National Center for Complementary and Alternative Medicine; National Cancer Institute FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism (grant K01 AA019996 to M.E.), the National Center for Complementary and Alternative Medicine (to S.J.P.), and the National Cancer Institute (to A.S.G.). NR 37 TC 5 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2013 VL 42 IS 4 BP 655 EP 662 DI 10.1097/MPA.0b013e3182762928 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126XF UT WOS:000317655200014 PM 23271397 ER PT J AU Carrion, IV Nedjat-Haiem, FR Martinez-Tyson, D Castaneda, H AF Carrion, Iraida V. Nedjat-Haiem, Frances R. Martinez-Tyson, Dinorah Castaneda, Heide TI Advance care planning among Colombian, Mexican, and Puerto Rican women with a cancer diagnosis SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Advance care planning; Latina; Cancer; Health decisions ID HEALTH; DISPARITIES; LIFE; END; PREFERENCES; DISCUSSIONS; HISPANICS; ATTITUDES; CULTURE; CUBANS AB Limited knowledge exists pertaining to advance care planning (ACP) among Colombian, Mexican, and Puerto Rican women with a cancer diagnosis living in Central Florida, in the USA. The purpose of the study is to identify factors that facilitated the completion of ACP and decisions making patterns among the three groups of Latinas. The research method used was an exploratory qualitative in-depth open-ended semi-structured interview with a grounded theoretical approach and thematic analysis. The interviews were conducted in Spanish with a purposeful sample of 45 Latinas (15 in each group) diagnosed with cancer. A total of ten women (22 %) in the study documented at least one form of ACP. Thirty-five women identified obstacles to accessing information regarding ACP, relating this to insurance and financial factors. Among the Colombian women, one completed a living will, health care surrogate, and power of attorney (all forms of ACP), and three just a living will. Two Puerto Rican women completed all, two a living will, and one both a living will and an enduring power of attorney. Only one Mexican woman completed a living will. This study identifies a knowledge gap regarding ACP among Latina women with cancer diagnosis living in Central Florida, in the USA. Differences between the three groups exist as a result of migration/immigration history, family support, education, English language proficiency, income, knowledge gaps, and information ascertained by medical and health professionals. These differences contribute to their readiness, receptiveness, and willingness to engage in documenting a living will, a health care surrogate, and an enduring power of attorney for health decisions. C1 [Carrion, Iraida V.] Univ S Florida, Sch Social Work, Tampa, FL 33612 USA. [Nedjat-Haiem, Frances R.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Martinez-Tyson, Dinorah] Univ S Florida, Dept Child & Family, Tampa, FL USA. [Castaneda, Heide] Univ S Florida, Dept Anthropol, Tampa, FL 33620 USA. RP Carrion, IV (reprint author), Univ S Florida, Sch Social Work, 13301 Bruce B Downs Blvd MHC 1438, Tampa, FL 33612 USA. EM icarrion@usf.edu OI Carrion, Iraida/0000-0003-4076-6644 FU Division of Population Sciences; H. Lee Moffitt Cancer Center and Research Institute; Division for Equal Health, University of South Florida in Tampa, FL; National Institute of Health [P20 MDD00375-01] FX The authors would like to thank Dr. Lee Green and Dr. Richard Roetzheim for their support and the Latina women who generously participated in the study. They also thank Ingrid Asmar and Milagros Porter for all their contributions as research assistants. This study was supported by the Division of Population Sciences, H. Lee Moffitt Cancer Center and Research Institute and the Division for Equal Health, University of South Florida in Tampa, FL, National Institute of Health grant number P20 MDD00375-01. NR 39 TC 4 Z9 4 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAY PY 2013 VL 21 IS 5 BP 1233 EP 1239 DI 10.1007/s00520-012-1652-z PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 117OK UT WOS:000316962600005 PM 23192672 ER PT J AU Boyce, R Lenhart, A Kroeger, A Velayudhan, R Roberts, B Horstick, O AF Boyce, R. Lenhart, A. Kroeger, A. Velayudhan, R. Roberts, B. Horstick, O. TI Bacillus thuringiensis israelensis (Bti) for the control of dengue vectors: systematic literature review SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE dengue; vector control; Bacillus thuringiensis israelensis; Aedes AB Objective To systematically review the literature on the effectiveness of Bacillus thuringiensis israelensis (Bti), when used as a single agent in the field, for the control of dengue vectors. Method Systematic literature search of the published and grey literature was carried out using the following databases: MEDLINE, EMBASE, Global Health, Web of Science, the Cochrane Library, WHOLIS, ELDIS, the New York Academy of Medicine Gray Literature Report, Africa-Wide and Google. All results were screened for duplicates and assessed for eligibility. Relevant data were extracted, and a quality assessment was conducted using the CONSORT 2010 checklist. Results Fourteen studies satisfied the eligibility criteria, incorporating a wide range of interventions and outcome measures. Six studies were classified as effectiveness studies, and the remaining eight examined the efficacy of Bti in more controlled settings. Twelve (all eight efficacy studies and 4 of 6 effectiveness studies) reported reductions in entomological indices with an average duration of control of 24weeks. The two effectiveness studies that did not report significant entomological reductions were both cluster-randomised study designs that utilised basic interventions such as environmental management or general education on environment control practices in their respective control groups. Only one study described a reduction in entomological indices together with epidemiological data, reporting one dengue case in the treated area compared to 15 dengue cases in the untreated area during the observed study period. Conclusion While Bti can be effective in reducing the number of immature Aedes in treated containers in the short term, there is very limited evidence that dengue morbidity can be reduced through the use of Bti alone. There is currently insufficient evidence to recommend the use of Bti as a single agent for the long-term control of dengue vectors and prevention of dengue fever. Further studies examining the role of Bti in combination with other strategies to control dengue vectors are warranted. C1 [Boyce, R.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Lenhart, A.; Kroeger, A.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Kroeger, A.] World Hlth Org, Special Programme Res & Training Trop Dis, Geneva, Switzerland. [Velayudhan, R.] World Hlth Org, Dept Control Neglected Trop Dis, Geneva, Switzerland. [Roberts, B.] London Sch Hyg & Trop Med, London WC1, England. [Horstick, O.] Inst Publ Hlth, Heidelberg, Germany. [Horstick, O.] Heidelberg Univ, D-69120 Heidelberg, Germany. RP Horstick, O (reprint author), Heidelberg Univ, Inst Publ Hlth, INF 324, D-69120 Heidelberg, Germany. EM Olaf.Horstick@Uni-Heidelberg.de OI Kroeger, Axel/0000-0001-8438-2904; Boyce, Ross/0000-0002-9489-6324 NR 0 TC 21 Z9 23 U1 3 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD MAY PY 2013 VL 18 IS 5 BP 564 EP 577 DI 10.1111/tmi.12087 PG 14 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 123VZ UT WOS:000317420800006 PM 23527785 ER PT J AU Korman, JB Fisher, DE AF Korman, John B. Fisher, David E. TI Developing melanoma therapeutics: overview and update SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Review ID KINASE KINASE-1/2 INHIBITOR; BRAF V600E MUTATION; METASTATIC MELANOMA; CUTANEOUS MELANOMA; RAF INHIBITORS; SOLID TUMORS; CANCER-IMMUNOTHERAPY; ACQUIRED-RESISTANCE; IMPROVED SURVIVAL; CTLA-4 BLOCKADE AB Melanoma is a common, often deadly malignancy, historically associated with limited treatment options for advanced disease. In recent years, systems-based research has resulted in significant clinical advancements. Strategic inhibition of mutated oncoproteins and targeting of immune checkpoints have emerged as very promising approaches. Vemurafenib, which received US Food and Drug Administration (FDA) approval in 2011, selectively inhibits BRAFV600E, a hyperactivated mutant signaling kinase in the mitogen-activated protein kinase (MAPK) pathway. Another recently FDA-approved drug, ipilimumab, blocks the cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway from inhibiting T cell activation. Despite this apparent progress, compelling challenges remain for both researchers and clinicians. Responses to therapy remain unacceptably incomplete and, in most cases, resistance mechanisms quickly develop that lead to relapse and subsequent patient mortality. Combining therapeutic modalities may increase the percentage of responding patients as well as the magnitude and durability of response. Notably, combined therapies involving selective BRAF inhibitors (SBIs) and other inhibitors of MAPK-dependent or MAPK-independent resistance pathways appear particularly promising. Preclinical and clinical studies are needed to comprehensively evaluate the optimal combinations of therapies, to identify melanoma subtypes that will be most responsive, and to determine optimal dosing, timing, and route of delivery. WIREs Syst Biol Med 2013, 5:257271. doi: 10.1002/wsbm.1210 For further resources related to this article, please visit the WIREs website. C1 [Korman, John B.; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dfisher3@partners.org NR 85 TC 8 Z9 8 U1 1 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5094 EI 1939-005X J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD MAY-JUN PY 2013 VL 5 IS 3 BP 257 EP 271 DI 10.1002/wsbm.1210 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 126ID UT WOS:000317606600001 PM 23408545 ER PT J AU Ananthakrishnan, AN McGinley, EL AF Ananthakrishnan, A. N. McGinley, E. L. TI Weekend hospitalisations and post-operative complications following urgent surgery for ulcerative colitis and Crohn's disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; POPULATION-BASED COHORT; SPECIALIST CARE; MORTALITY; COLECTOMY; IMPACT; OUTCOMES; ADMISSION; VOLUME; RISK AB Background There is increasing complexity in the management of patients with acute severe exacerbation of inflammatory bowel disease [IBD; Crohn's disease (CD), ulcerative colitis (UC)] with frequent requirement for urgent surgery. Aim To determine whether a weekend effect exists for IBD care in the United States. Methods We used data from the Nationwide Inpatient Sample (NIS) 2007, the largest all-payer hospitalisation database in the United States. Discharges with a diagnosis of CD or UC who underwent urgent intestinal surgery within 2days of hospitalisation were identified using the appropriate ICD-9 codes. The independent effect of admission on a weekend was examined using multivariate logistic regression adjusting for potential confounders. Results Our study included 7,112 urgent intestinal surgeries in IBD patients, 21% of which occurred following weekend admissions. There was no difference in disease severity between weekend and weekday admissions. Post-operative complications were more common following weekend than weekday hospitalisations in UC [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.012.90]. The most common post-operative complication was post-operative infections (Weekend 30% vs. weekday 20%, P=0.04). The most striking difference between weekend and weekday hospitalisations was noted for needing repeat laparotomy (OR 11.5), mechanical wound complications (OR 10.03) and pulmonary complications (OR 2.22). In contrast, occurrence of any post-operative complication in CD was similar between weekday and weekend admissions. Conclusion Patients with UC hospitalised on a weekend undergoing urgent surgery within 2days have an increased risk for post-operative complications, in particular mechanical wound complications, need for repeat laparotomy and post-operative infections. C1 [Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ananthakrishnan, A. N.] Harvard Univ, Sch Med, Boston, MA USA. [McGinley, E. L.] Med Coll Wisconsin, Ctr Patient Care & Outcomes & Res, Milwaukee, WI 53226 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institutes of Health [K23 DK097142] FX Declaration of funding interests: Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). NR 31 TC 10 Z9 10 U1 0 U2 5 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 MAY PY 2013 VL 37 IS 9 BP 895 EP 904 DI 10.1111/apt.12272 PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 118ZH UT WOS:000317065600005 PM 23451882 ER PT J AU Huddle, TS AF Huddle, Thomas S. TI Don't Ban the Sunset in Pharmaceutical Advertising If It Doesn't Darken the Sky SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 Univ Alabama, Bimingham Sch Med, Birmingham VA Med Ctr, Tuscaloosa, AL 35487 USA. RP Huddle, TS (reprint author), Univ Alabama, Bimingham Sch Med, Birmingham VA Med Ctr, 700 19th St S, Tuscaloosa, AL 35487 USA. EM thuddle@uab.edu NR 16 TC 1 Z9 1 U1 0 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD MAY 1 PY 2013 VL 13 IS 5 BP 27 EP 30 DI 10.1080/15265161.2013.776141 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 120NI UT WOS:000317176900014 PM 23557043 ER PT J AU Rahbari, NN Weitz, J AF Rahbari, Nuh N. Weitz, Juergen TI Hyaluronic Acid as a Marker of Sinusoidal Obstruction Syndrome after Oxaliplatin-based Chemotherapy for Colorectal Liver Metastases: Don't Forget the Tumor SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID MULTICENTER RANDOMIZED-TRIAL; 1ST-LINE TREATMENT; PREOPERATIVE CHEMOTHERAPY; PROGNOSTIC-FACTOR; PHASE-III; CANCER; FLUOROURACIL; LEUCOVORIN; BEVACIZUMAB; RESECTION C1 [Rahbari, Nuh N.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Rahbari, Nuh N.] Harvard Univ, Sch Med, Boston, MA USA. [Weitz, Juergen] Univ Hosp Carl Gustav Carus Tech Univ Dresden, Dept Visceral Thorac & Vasc Surg, Dresden, Germany. RP Rahbari, NN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. EM juergen.weitz@uniklinikum-dresden.de NR 25 TC 1 Z9 1 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2013 VL 20 IS 5 BP 1405 EP 1407 DI 10.1245/s10434-013-2916-7 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 122HC UT WOS:000317308200002 PM 23463087 ER PT J AU Baldini, EH Lapidus, MR Wang, Q Manola, J Orgill, DP Pomahac, B Marcus, KJ Bertagnolli, MM Devlin, PM George, S Abraham, J Ferrone, ML Ready, JE Raut, CP AF Baldini, Elizabeth H. Lapidus, Michelle R. Wang, Qian Manola, Judith Orgill, Dennis P. Pomahac, Bohdan Marcus, Karen J. Bertagnolli, Monica M. Devlin, Phillip M. George, Suzanne Abraham, John Ferrone, Marco L. Ready, John E. Raut, Chandrajit P. TI Predictors for Major Wound Complications Following Preoperative Radiotherapy and Surgery for Soft-Tissue Sarcoma of the Extremities and Trunk: Importance of Tumor Proximity to Skin Surface SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID ADJUVANT RADIATION-THERAPY; POSTOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIAL; LIMB FUNCTION; PHASE-II; MORBIDITY; RESECTION AB Preoperative and postoperative RT for the treatment of high-grade soft-tissue sarcoma result in similar local control and overall survival rates, but morbidities differ. Postoperative RT is associated with a higher rate of long-term fibrosis, edema, and joint stiffness. Preoperative RT is associated with higher rates of wound complications. It is important to identify predictors for major wound complications (MWC) and to develop strategies to minimize this outcome. We reviewed our experience to determine predictors for MWC following preoperative radiotherapy (RT) and surgery for soft-tissue sarcoma. Between January 2006 and May 2011, 103 patients with soft-tissue sarcoma of the extremities and trunk were treated with preoperative RT followed by surgery. MWCs were defined as those requiring operative or prolonged nonoperative management. Fisher's exact test was used to compare rates. Logistic regression was used for multivariable analysis of factors potentially associated with MWCs. Median tumor size was 8.4 cm (range 2-25). All patients had wide or radical resections. Wound closures were primary in 70 %, a vascularized flap in 27 %, and split-thickness skin graft (STSG) in 3 %. There were 36 MWCs (35 %). Significant predictors for MWCs on univariate analysis included diabetes, tumors > 10 cm, tumors < 3 mm from skin surface, and vascularized flap/STSG closure. The same four variables were significant predictors on multivariable analysis. MWCs following preoperative RT and surgery were common. Tumor proximity to skin surface < 3 mm is a previously unreported independent predictor, and further strategies to minimize wound complications are needed. C1 [Baldini, Elizabeth H.; Marcus, Karen J.; Devlin, Phillip M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Lapidus, Michelle R.; Bertagnolli, Monica M.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Orgill, Dennis P.; Pomahac, Bohdan] Brigham & Womens Hosp, Dept Plast Surg, Boston, MA 02115 USA. [Ferrone, Marco L.; Ready, John E.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Baldini, Elizabeth H.; Lapidus, Michelle R.; Marcus, Karen J.; Bertagnolli, Monica M.; Devlin, Phillip M.; George, Suzanne; Ferrone, Marco L.; Ready, John E.; Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Wang, Qian] Beijing Novartis Pharma Co Ltd, Beijing, Peoples R China. [Manola, Judith] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Abraham, John] Thomas Jefferson Univ, Dept Orthoped Surg, Rothman Inst, Philadelphia, PA 19107 USA. [George, Suzanne] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Baldini, EH (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM ebaldini@partners.org OI Orgill, Dennis/0000-0002-8279-7310 NR 31 TC 26 Z9 29 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2013 VL 20 IS 5 BP 1494 EP 1499 DI 10.1245/s10434-012-2797-1 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 122HC UT WOS:000317308200014 PM 23242820 ER PT J AU Gilmore, D Schulz, M Liu, R Zubris, KAV Padera, RF Catalano, PJ Grinstaff, MW Colson, YL AF Gilmore, Denis Schulz, Morgan Liu, Rong Zubris, Kimberly Ann V. Padera, Robert F. Catalano, Paul J. Grinstaff, Mark W. Colson, Yolonda L. TI Cytoreductive Surgery and Intraoperative Administration of Paclitaxel-loaded Expansile Nanoparticles Delay Tumor Recurrence in Ovarian Carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; STAGE-III OVARIAN; INTRAPERITONEAL CISPLATIN; CANCER-THERAPY; DRUG-DELIVERY; CHEMOTHERAPY; SURVIVAL; TRIAL; PH; CARBOPLATIN AB Locoregional recurrence significantly impacts survival and quality of life in patients with ovarian carcinoma. We hypothesize that local administration of paclitaxel-loaded expansile nanoparticles (pax-eNP) at the time of cytoreductive surgery decreases local tumor recurrence. In vitro cytotoxicity of pax-eNP was assessed against both the OVCAR-3 human ovarian cancer cell line and tumor cells isolated from a malignant pleural effusion from a patient with multidrug-resistant ovarian cancer. A murine xenogenic model involving surgical cytoreduction of established OVCAR-3 intra-abdominal tumor was used to evaluate in vivo efficacy of intraoperative intraperitoneal (IP) injection of 10 mg/kg of paclitaxel either as pax-eNP or paclitaxel in Cremophor EL/ethanol solution (pax-C/E) versus empty eNP controls. Cytoreductive surgery and intraoperative treatment were performed 4 weeks after established tumor. All animals were sacrificed when empty eNP controls displayed extensive evidence of disease progression. Labeled-eNP entered tumor cells in vitro within 4 h and specifically accumulated at sites of tumor in vivo. Pax-eNP exhibited dose-dependent cytotoxicity in both OVCAR-3 and patient tumor cells isolated from a malignant pleural effusion and effectively prevented tumor recurrence following debulking (p = 0.003 vs. empty eNP). Furthermore, pax-eNP-treated animals did not develop severe recurrent carcinomatosis compared with 43 % of the pax-C/E-treated cohort, suggesting that single-dose intracavitary pax-eNP is more effective than an equivalent dose of pax-C/E. Expansile nanoparticles readily enter human ovarian tumor cells and localize to sites of tumor in vivo with pax-eNP cytotoxicity resulting in superior inhibition of locoregional tumor recurrence following cytoreductive surgery. C1 [Gilmore, Denis; Schulz, Morgan; Liu, Rong; Colson, Yolonda L.] Brigham & Womens Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02115 USA. [Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zubris, Kimberly Ann V.; Grinstaff, Mark W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Zubris, Kimberly Ann V.; Grinstaff, Mark W.] Boston Univ, Dept Chem, Boston, MA 02215 USA. RP Gilmore, D (reprint author), Brigham & Womens Hosp, Dept Surg, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM dgilmor1@bidmc.harvard.edu OI Grinstaff, Mark/0000-0002-5453-3668 FU Center for Integration of Medicine and Innovative Technology, the Cross-Disciplinary Training in Nanotechnology for Cancer, NIH [R25 CA153955]; NSF [DMR-1006601] FX The authors express their appreciation to Brigham and Women's Hospital, the Dana-Farber Cancer Institute Animal Facility, and Beth Israel Deaconess Medical Center Confocal Imaging Core who kindly provided their expertise and guidance. This work was supported by the Center for Integration of Medicine and Innovative Technology, the Cross-Disciplinary Training in Nanotechnology for Cancer, NIH R25 CA153955, and the NSF DMR-1006601. NR 35 TC 8 Z9 9 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2013 VL 20 IS 5 BP 1684 EP 1693 DI 10.1245/s10434-012-2696-5 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 122HC UT WOS:000317308200039 PM 23128939 ER PT J AU Liu, SH Howell, PM Riker, AI AF Liu, Suhu Howell, Paul M. Riker, Adam I. TI Up-Regulation of miR-182 Expression after Epigenetic Modulation of Human Melanoma Cells SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID MALIGNANT-MELANOMA; DNA METHYLATION; HUMAN CANCER; CPG ISLANDS; MICRORNA; METASTASIS; IDENTIFICATION; 5-AZACYTIDINE; LINES AB We sought to investigate the epigenetic regulation of microRNAs (miRNAs) in melanoma. We treated two highly metastatic human melanoma cell lines, C8161.9 and WM266-4, with the demethylating agents DAC (5-aza-2'-deoxycytidine) and trichostatin A. Locked nucleic acid-based miRNA expression profiling was utilized to examine the differential expression of miRNAs before and after treatment. We found that miR-182, a miRNA with oncogenic properties, was significantly up-regulated in human melanoma cells after epigenetic modulation. Genome sequence analysis revealed the presence of a prominent CpG island 8-10 kb upstream of mature miR-182. Methylation analysis showed that this genomic region was exclusively methylated in melanoma cells but not in human melanocytes, skin, or peripheral blood mononuclear cells. These results indicate that an epigenetic mechanism is likely involved in modulating the expression level of miR-182 in melanoma, and increased expression of oncogenic-like miR-182 could be a concern for melanoma patients after epigenetic therapy. C1 [Liu, Suhu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Howell, Paul M.] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. [Riker, Adam I.] Advocate Christ Med Ctr & Canc Inst, Oak Lawn, IL USA. RP Liu, SH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM ariker1234@gmail.com FU Abraham A. Mitchell Clinical Research Scholar Fund FX A.I.R. is the recipient of the Abraham A. Mitchell Clinical Research Scholar Fund, which provided the necessary funding and resources for the completion of the research described in this article. NR 32 TC 16 Z9 17 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2013 VL 20 IS 5 BP 1745 EP 1752 DI 10.1245/s10434-012-2467-3 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 122HC UT WOS:000317308200047 PM 22752337 ER PT J AU Pineles, SL Rasmusson, AM Yehuda, R Lasko, NB Macklin, ML Pitman, RK Orr, SP AF Pineles, Suzanne L. Rasmusson, Ann M. Yehuda, Rachel Lasko, Natasha B. Macklin, Michael L. Pitman, Roger K. Orr, Scott P. TI Predicting emotional responses to potentially traumatic events from pre-exposure waking cortisol levels: a longitudinal study of police and firefighters SO ANXIETY STRESS AND COPING LA English DT Article DE cortisol; psychophysiology; trauma; negative affect; neuroticism; stress ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY REPLICATION; MISSISSIPPI PTSD SCALE; DSM-IV DISORDERS; PSYCHOPHYSIOLOGICAL ASSESSMENT; SALIVARY CORTISOL; URINARY CORTISOL; CIVILIAN VERSION; COMBAT VETERANS; FEAR AB There is a large literature demonstrating that individuals who have experienced traumatic events have alterations in the hypothalamic-pituitary-adrenal (HPA) axis. However, the existing literature does not address the extent to which these alterations represent pre-existing risk factors for developing psychopathology upon exposure to a significant stressor. In the current study, we examined the relationship between waking salivary cortisol level and physiological, personality, and psychological measures in 60 firefighters and police trainees during training, and then again after exposure to a highly stressful, potentially traumatic event (PTE). Waking cortisol was negatively associated with neuroticism, but positively associated with physiological reactivity to loud tones and fear conditioning when assessed during training. Longitudinally, there were significant negative correlations between pre-PTE waking cortisol and post-PTE negative mood and anxiety symptoms, but a positive correlation (trend) between pre-PTE waking cortisol and post-PTE physiological reactivity during recollection of the PTE. Thus, waking cortisol level may serve to predict divergent types of emotional sequelae following PTEs. C1 [Pineles, Suzanne L.; Rasmusson, Ann M.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Pineles, Suzanne L.; Rasmusson, Ann M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat & Neurobiol, Bronx, NY USA. [Yehuda, Rachel] James J Peters Bronx VA, Dept Psychiat, Bronx, NY USA. [Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lasko, Natasha B.; Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. [Lasko, Natasha B.; Macklin, Michael L.; Orr, Scott P.] Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. RP Orr, SP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM scott_orr@hms.harvard.edu FU NIMH NIH HHS [R01-MH60315] NR 56 TC 8 Z9 10 U1 4 U2 38 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PD MAY 1 PY 2013 VL 26 IS 3 BP 241 EP 253 DI 10.1080/10615806.2012.672976 PG 13 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 121XD UT WOS:000317277600001 PM 22574657 ER PT J AU Clancy, CJ Nguyen, MH AF Clancy, Cornelius J. Nguyen, M. Hong TI Finding the "Missing 50%" of Invasive Candidiasis: How Nonculture Diagnostics Will Improve Understanding of Disease Spectrum and Transform Patient Care SO CLINICAL INFECTIOUS DISEASES LA English DT Review DE invasive candidiasis; candidemia; diagnostic; PCR; beta-D-glucan ID POLYMERASE-CHAIN-REACTION; D-GLUCAN ASSAY; REAL-TIME PCR; BLOOD CULTURES; SYSTEMIC CANDIDIASIS; FUNGAL-INFECTIONS; ANTIMANNAN ANTIBODIES; HEPATIC CANDIDIASIS; ANTIFUNGAL AGENTS; CANCER-PATIENTS AB Blood cultures are limited for diagnosing invasive candidiasis by poor sensitivity and slow turn-around time. New diagnostics are needed to complement cultures, in particular to identify the "missing 50%" of patients who are blood culture-negative. Mannan/anti-mannan immunoglobulin G, beta-D-glucan (BDG) and polymerase chain reaction (PCR) assays can diagnose candidemia before blood cultures and show promising sensitivity/specificity, but they are not widely investigated in blood culture-negative, deep-seated candidiasis. In a recent study, BDG and PCR were superior to blood cultures in deep-seated candidiasis, suggesting they may identify currently undiagnosed patients and expand our understanding of disease spectrum. Positive predictive values of nonculture tests are limited by the low prevalence of invasive candidiasis, which mandates that results be interpreted judiciously. When used as biomarkers that assess a patient's risk of having invasive candidiasis, tests will facilitate preemptive antifungal strategies. Because negative predictive values are excellent, tests will also be useful for ruling out invasive candidiasis and discontinuing unnecessary antifungal therapy. C1 [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Clancy, Cornelius J.; Nguyen, M. Hong] Univ Pittsburgh, Pittsburgh, PA 15261 USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Scaife Hall,Ste 869,3550 Terrace St, Pittsburgh, PA 15261 USA. EM cjc76@pitt.edu FU ClinicalTrials.gov [NCT01525095]; ViraCor-IBT Laboratories for the BDG/PCR FX C. J. C. is a site principal investigator for a multicenter trial of the T2 Candida Bioassay for candidemia (T2 Biosystems; ClinicalTrials.gov identifier: NCT01525095). M. H. N. received investigator-initiated research funding from ViraCor-IBT Laboratories for the BDG/PCR study cited in this paper [31]. NR 40 TC 88 Z9 91 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2013 VL 56 IS 9 BP 1284 EP 1292 DI 10.1093/cid/cit006 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 123QC UT WOS:000317404300015 PM 23315320 ER PT J AU Dudley, MN Ambrose, PG Bhavnani, SM Craig, WA Ferraro, MJ Jones, RN AF Dudley, Michael N. Ambrose, Paul G. Bhavnani, Sujata M. Craig, William A. Ferraro, Mary Jane Jones, Ronald N. CA Antimicrobial Susceptibility Testi TI Background and Rationale for Revised Clinical and Laboratory Standards Institute Interpretive Criteria (Breakpoints) for Enterobacteriaceae and Pseudomonas aeruginosa: I. Cephalosporins and Aztreonam SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE breakpoints; Enterobacteriaceae; cephalosporins; Pseudomonas; CLSI ID PHARMACODYNAMICS; INFECTIONS; ORGANISMS; OUTCOMES AB Widespread resistance in Enterobacteriaceae and Pseudomonas aeruginosa to cephalosporin and monobactam antibiotics due to extended-spectrum beta-lactamases (ESBLs) has resulted in the need for reassessment of the interpretative criteria (breakpoints) established for these agents more than 2 decades ago. Following extensive evaluation, the Clinical and Laboratory Standards Institute recently adopted and published new breakpoints for these agents for use in clinical laboratories and provided updated recommendations for use of the ESBL screening test. This paper summarizes the background and supportive rationale for new interpretative criteria for cephalosporins and aztreonam for testing Enterobacteriaceae. C1 [Dudley, Michael N.] Rempex Pharmaceut, San Diego, CA 92121 USA. [Ambrose, Paul G.; Bhavnani, Sujata M.] Inst Clin Pharmacodynam Inc, Latham, NY USA. [Craig, William A.] Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. [Ferraro, Mary Jane] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ferraro, Mary Jane] Harvard Univ, Sch Med, Boston, MA USA. [Jones, Ronald N.] JMI Labs, N Liberty, IA USA. RP Dudley, MN (reprint author), Rempex Pharmaceut, 11535 Sorrento Valley Rd, San Diego, CA 92121 USA. EM mdudley@rempexpharma.com NR 14 TC 56 Z9 57 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2013 VL 56 IS 9 BP 1301 EP 1309 DI 10.1093/cid/cit017 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 123QC UT WOS:000317404300018 PM 23334813 ER PT J AU Franke, MF Kaigamba, F Socci, AR Hakizamungu, M Patel, A Bagiruwigize, E Niyigena, P Walker, KDC Epino, H Binagwaho, A Mukherjee, J Farmer, PE Rich, ML AF Franke, Molly F. Kaigamba, Felix Socci, Adrienne R. Hakizamungu, Massudi Patel, Anita Bagiruwigize, Emmanuel Niyigena, Peter Walker, Kelly D. C. Epino, Henry Binagwaho, Agnes Mukherjee, Joia Farmer, Paul E. Rich, Michael L. TI Improved Retention Associated With Community-Based Accompaniment for Antiretroviral Therapy Delivery in Rural Rwanda SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE retention; community health workers; nutrition; Africa; HIV ID SUB-SAHARAN AFRICA; TREATMENT OUTCOMES; TREATMENT PROGRAM; HIV; ADHERENCE; ADULTS; HAART; RELIABILITY; DEPRESSION; VALIDITY AB Background. Minimizing death and ensuring high retention and good adherence remain ongoing challenges for human immunodeficiency virus (HIV) treatment programs. We examined whether the addition of community-based accompaniment (characterized by daily home visits from a community health worker, directly observed treatment, nutritional support, transportation stipends, and other support as needed) to the Rwanda national model for antiretroviral therapy (ART) delivery would improve retention in care, viral load suppression, and change in CD4 count, relative to the national model alone. Methods. We conducted a prospective observational cohort study among 610 HIV-infected adults initiating ART in 1 of 2 programs in rural Rwanda. Psychosocial and clinical characteristics were recorded at ART initiation. Death, treatment retention, and plasma viral load were assessed at 1 year. CD4 count was evaluated at 6-month intervals. Multivariable regression models were used to adjust for baseline differences between the 2 populations. Results. Eighty-five percent and 79% of participants in the community-based and clinic-based programs, respectively, were retained with viral load suppression at 1 year. After adjusting for CD4 count, depression, physical health quality of life, and food insecurity, community-based accompaniment was protective against death or loss to follow-up during the first year of ART (hazard ratio, 0.17; 95% confidence interval [CI],.09-.35; P <.0001). In a second multivariable analysis, individuals receiving accompaniment were more likely to be retained with a suppressed viral load at 1 year (risk ratio: 1.15; 95% CI, 1.03-1.27; P =.01). Conclusions. These findings indicate that community-based accompaniment is effective in improving retention, when added to a clinic-based program with fewer patient support mechanisms. C1 [Franke, Molly F.; Binagwaho, Agnes; Mukherjee, Joia; Farmer, Paul E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Kaigamba, Felix; Bagiruwigize, Emmanuel] Ruhengeri Hosp, Rwanda Minist Hlth, Ruhengeri, Rwanda. [Franke, Molly F.; Socci, Adrienne R.; Hakizamungu, Massudi; Patel, Anita; Niyigena, Peter; Walker, Kelly D. C.; Epino, Henry; Mukherjee, Joia; Farmer, Paul E.; Rich, Michael L.] Partners Hlth Inshuti Mu Buzima, Rwinkwavu, Rwanda. [Binagwaho, Agnes] Minist Hlth Rwanda, Kigali, Rwanda. [Epino, Henry; Mukherjee, Joia; Farmer, Paul E.; Rich, Michael L.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Epino, Henry] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Franke, MF (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM molly_franke@hms.harvard.edu FU Doris Duke Charitable Foundation FX This work was supported by the Doris Duke Charitable Foundation. NR 41 TC 33 Z9 33 U1 0 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2013 VL 56 IS 9 BP 1319 EP 1326 DI 10.1093/cid/cis1193 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 123QC UT WOS:000317404300020 PM 23249611 ER PT J AU Jena, AB Karaca-Mandic, P Weaver, L Seabury, SA AF Jena, Anupam B. Karaca-Mandic, Pinar Weaver, Lesley Seabury, Seth A. TI Predicting New Diagnoses of HIV Infection Using Internet Search Engine Data SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Karaca-Mandic, Pinar; Weaver, Lesley] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Seabury, Seth A.] RAND Corp, Santa Monica, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu NR 5 TC 7 Z9 7 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2013 VL 56 IS 9 BP 1352 EP 1353 DI 10.1093/cid/cit022 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 123QC UT WOS:000317404300028 PM 23334812 ER PT J AU Dong, Y Wu, X Zhang, G Xu, Z Zhang, Y Gautam, V Kovacs, DM Wu, A Yue, Y Xie, Z AF Dong, Y. Wu, X. Zhang, G. Xu, Z. Zhang, Y. Gautam, V. Kovacs, D. M. Wu, A. Yue, Y. Xie, Z. TI Isoflurane Facilitates Synaptic NMDA Receptor Endocytosis in Mice Primary Neurons SO CURRENT MOLECULAR MEDICINE LA English DT Article DE Alzheimer's disease; anesthesia; cognition; endocytosis; isoflurane; NMDA ID ALZHEIMERS-DISEASE; AMYLOID-BETA; INDUCED APOPTOSIS; ANESTHESIA; CASPASE-3; ACTIVATION; EXPOSURE; SURGERY; SEVOFLURANE; PRESENILINS AB Inhalation anesthetic isoflurane has been reported to induce caspase activation and accumulation of beta-amyloid (A beta), however, the down-stream consequences of these effects are largely unknown. Isoflurane has also been shown to impair learning and memory, however, the up-stream mechanisms of these effects remain largely to be determined. Facilitation of synaptic NMDA receptor endocytosis can reduce synaptic function, leading to learning and memory impairment. We therefore set out to determine the effects of isoflurane on synaptic NMDA receptor endocytosis. Primary neurons from wild-type and Alzheimer's disease transgenic mice were treated with 2% isoflurane for six hours. Synaptic surface levels of NMDA receptor 2B (NR2B) and NR2B internalization were determined by surface and cleavable biotinylation assay, western blot analysis and immunofluorescence. Here we show that isoflurane can induce caspase-3 activation, increase levels of beta-site amyloid precursor protein-cleaving enzyme and cause accumulation of A beta in the primary neurons. Isoflurane facilitates synaptic NR2B endocytosis as evidenced by reducing surface NR2B levels, increasing NR2B internalization, and decreasing the ratio of synaptic surface NR2B to synapsin in mice primary neurons. Moreover, caspase activation inhibitor Z-VAD and gamma-secretase inhibitor L-685,458 attenuated the isoflurane-facilitated NR2B endocytosis. These results suggest that isoflurane induces caspase activation and A beta accumulation, leading to facilitation of synaptic NMDA receptor endocytosis, which potentially serve as the upstream mechanism of the isoflurane-induced impairment of learning and memory. These findings will encourage further studies to determine the underlying mechanism by which isoflurane and other anesthetics promote Alzheimer's disease neuropathogenesis and induce cognitive dysfunction. C1 [Dong, Y.; Xu, Z.; Zhang, Y.; Xie, Z.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Dong, Y.; Xu, Z.; Zhang, Y.; Gautam, V.; Kovacs, D. M.; Xie, Z.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wu, X.; Zhang, G.] China Med Univ, Fac Forens Med, Dept Forens Pathol, Shenyang 110001, Peoples R China. [Gautam, V.; Kovacs, D. M.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Neurobiol Dis Lab, Charlestown, MA 02129 USA. [Wu, A.; Yue, Y.] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing 100020, Peoples R China. RP Xie, Z (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU (National Institutes of Health), USA [K08NS048140, R21AG029856, R21AG038994, R01 GM088801, R01 AG041274]; Jahnigen Career Development Award (American Geriatrics Society); Investigator Initiated Research Grant (Alzheimer's Association); Cure Alzheimer's Fund, USA; National Science Foundation Oversea young scholar collaboration research award, P.R. China [NSF30928026] FX This research was supported by K08NS048140, R21AG029856, R21AG038994, R01 GM088801, R01 AG041274 (National Institutes of Health), USA, Jahnigen Career Development Award (American Geriatrics Society), Investigator Initiated Research Grant (Alzheimer's Association), Cure Alzheimer's Fund (to Z.X.), USA; National Science Foundation Oversea young scholar collaboration research award NSF30928026, P.R. China (to Y.Y. and Z.X.). Department of Anesthesia, Critical Care and Pain Medicine in Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA generously provided isoflurane for the studies. NR 43 TC 3 Z9 4 U1 2 U2 21 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAY PY 2013 VL 13 IS 4 BP 488 EP 498 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 119SH UT WOS:000317117400003 PM 22950384 ER PT J AU Knaub, LA McCune, S Chicco, AJ Miller, M Moore, RL Birdsey, N Lloyd, MI Villarreal, J Keller, AC Watson, PA Reusch, JEB AF Knaub, Leslie A. McCune, Sylvia Chicco, Adam J. Miller, Matthew Moore, Russell L. Birdsey, Nicholas Lloyd, Monique I. Villarreal, Juan Keller, Amy C. Watson, Peter A. Reusch, Jane E. B. TI Impaired response to exercise intervention in the vasculature in metabolic syndrome SO DIABETES & VASCULAR DISEASE RESEARCH LA English DT Article DE Cyclic adenosine monophosphate response element binding protein; mitochondria; exercise; SHHF; diabetes; vasculature ID ELEMENT-BINDING PROTEIN; LOW CARDIORESPIRATORY FITNESS; MUSCLE CELL-PROLIFERATION; ZUCKER OBESE RATS; MITOCHONDRIAL BIOGENESIS; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; HEART-FAILURE; NITRIC-OXIDE; DISEASE RISK AB Physical activity decreases risk for diabetes and cardiovascular disease morbidity and mortality; however, the specific impact of exercise on the diabetic vasculature is unexamined. We hypothesized that an acute, moderate exercise intervention in diabetic and hypertensive rats would induce mitochondrial biogenesis and mitochondrial antioxidant defence to improve vascular resilience. SHHF/Mcc-fa(cp) lean (hypertensive) and obese (hypertensive, insulin resistant), as well as Sprague Dawley (SD) control rats were run on a treadmill for 8 days. In aortic lysates from SD rats, we observed a significant increase in subunit proteins from oxidative phosphorylation (OxPhos) complexes I-III, with no changes in the lean or obese SHHF rats. Exercise also increased the expression of mitochondrial antioxidant defence uncoupling protein 3 (UCP3) (p < 0.05) in SHHF lean rats, whereas no changes were observed in the SD or SHHF obese rats with exercise. We evaluated upstream signalling pathways for mitochondrial biogenesis, and only peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) significantly decreased in SHHF lean rats (p < 0.05) with exercise. In these experiments, we demonstrate absent mitochondrial induction with exercise exposure in models of chronic vascular disease. These findings suggest that chronic vascular stress results in decreased sensitivity of vasculature to the adaptive mitochondrial responses normally induced by exercise. C1 [Knaub, Leslie A.; Miller, Matthew; Birdsey, Nicholas; Lloyd, Monique I.; Villarreal, Juan; Keller, Amy C.; Watson, Peter A.; Reusch, Jane E. B.] Univ Colorado Denver, Div Endocrinol Diabet & Metab, Aurora, CO 80045 USA. [Knaub, Leslie A.; Miller, Matthew; Birdsey, Nicholas; Lloyd, Monique I.; Keller, Amy C.; Watson, Peter A.; Reusch, Jane E. B.] Denver VA Med Ctr, Dept Med, Denver, CO USA. [McCune, Sylvia; Moore, Russell L.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Chicco, Adam J.] Colorado State Univ, Dept Hlth & Exercise Sci, Ft Collins, CO 80523 USA. RP Reusch, JEB (reprint author), Univ Colorado Denver, Div Endocrinol Diabet & Metab, Anschutz Med Campus,12801 E 17th Ave,MS8106, Aurora, CO 80045 USA. EM jane.reusch@ucdenver.edu FU Department of Veterans Affairs Office of Research and Development; National Institutes of Health [HL14985, UL1 RR025780]; American Heart Association [0835545N] FX This work was supported by the Department of Veterans Affairs Office of Research and Development (Merit Review JEBR and PAW), National Institutes of Health (HL14985, UL1 RR025780, JEBR) and American Heart Association Grant (0835545N, AJC). NR 65 TC 8 Z9 8 U1 0 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1479-1641 J9 DIABETES VASC DIS RE JI Diabetes Vasc. Dis. Res. PD MAY PY 2013 VL 10 IS 3 BP 222 EP 238 DI 10.1177/1479164112459664 PG 17 WC Endocrinology & Metabolism; Peripheral Vascular Disease SC Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 122CR UT WOS:000317293900005 PM 23162060 ER EF