FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Engels, MC Rajarajan, K Feistritzer, R Sharma, A Nielsen, UB Schalij, MJ De Vries, AAF Pijnappels, DA Wu, SM AF Engels, M. C. Rajarajan, K. Feistritzer, R. Sharma, A. Nielsen, U. B. Schalij, M. J. De Vries, A. A. F. Pijnappels, D. A. Wu, S. M. TI IGF promotes cardiac lineage induction by selective expansion of cardiogenic mesoderm in vitro SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 31-SEP 04, 2013 CL Amsterdam, NETHERLANDS SP European Soc Cardiol C1 [Engels, M. C.; Rajarajan, K.; Feistritzer, R.; Wu, S. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharma, A.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Nielsen, U. B.] Silvercreek Pharmaceut, San Francisco, CA USA. [Schalij, M. J.; De Vries, A. A. F.; Pijnappels, D. A.] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2013 VL 34 SU 1 BP 929 EP 929 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 262OH UT WOS:000327744605466 ER PT J AU Magnusson, M Wang, T Hedblad, B Engstrom, G Ostling, G Gerszten, R Melander, O AF Magnusson, M. Wang, T. Hedblad, B. Engstrom, G. Ostling, G. Gerszten, R. Melander, O. TI High levels of arginine, citrulline and ADMA are independent predictors of cardiovascular disease SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 31-SEP 04, 2013 CL Amsterdam, NETHERLANDS SP European Soc Cardiol C1 [Magnusson, M.] Lund Univ, Skane Univ Hosp, Dept Heart Failure & Valvular Dis, Malmo, Sweden. [Wang, T.; Gerszten, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Hedblad, B.; Engstrom, G.; Ostling, G.; Melander, O.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2013 VL 34 SU 1 BP 1058 EP 1059 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 262OH UT WOS:000327744606409 ER PT J AU Evans, MC Paquet, AC Huang, W Napolitano, L Frantzell, A Toma, J Stawiski, EW Goetz, MB Petropoulos, CJ Whitcomb, J Coakley, E Haddad, M AF Evans, Mark C. Paquet, Agnes C. Huang, Wei Napolitano, Laura Frantzell, Arne Toma, Jonathan Stawiski, Eric W. Goetz, Matthew Bidwell Petropoulos, Christos J. Whitcomb, Jeannette Coakley, Eoin Haddad, Mojgan TI A CASE-BASED REASONING SYSTEM FOR GENOTYPIC PREDICTION OF HIV-1 CO-RECEPTOR TROPISM SO JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY LA English DT Article DE Tropism prediction; genotypic algorithm; HIV-1 co-receptor; V3 ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIDDEN MARKOV-MODELS; PHENOTYPE PREDICTION; CLINICAL MANAGEMENT; USAGE; INFECTION; SEQUENCE; DISEASE; ASSAY AB Accurate co-receptor tropism (CRT) determination is critical for making treatment decisions in HIV management. We created a genotypic tropism prediction tool by utilizing the case-based reasoning (CBR) technique that attempts to solve new problems through applying the solution from similar past problems. V3 loop sequences from 732 clinical samples with diverse characteristics were used to build a case library. Additional sequence and molecular properties of the V3 loop were examined and used for similarity assessment. A similarity metric was defined based on each attribute's frequency in the CXCR4-using viruses. We implemented three other genotype-based tropism predictors, support vector machines (SVM), position specific scoring matrices (PSSM), and the 11/25 rule, and evaluated their performance as the ability to predict CRT compared to Monogram's enhanced sensitivity Trofile (R) assay (ESTA). Overall concordance of the CBR based tropism prediction algorithm was 81%, as compared to ESTA. Sensitivity to detect CXCR4 usage was 90% and specificity was at 73%. In comparison, sensitivity of the SVM, PSSM, and the 11/25 rule were 85%, 81%, and 36% respectively while achieving a specificity of 90% by SVM, 75% by PSSM, and 97% by the 11/25 rule. When we evaluated these predictors in an unseen dataset, higher sensitivity was achieved by the CBR algorithm (87%), compared to SVM (82%), PSSM (76%), and the 11/25 rule (33%), while maintaining similar level of specificity. Overall this study suggests that CBR can be utilized as a genotypic tropism prediction tool, and can achieve improved performance in independent datasets compared to model or rule based methods. C1 [Evans, Mark C.; Paquet, Agnes C.; Stawiski, Eric W.; Haddad, Mojgan] Monogram Biosci Inc, Bioinformat Biostat, San Francisco, CA 94080 USA. [Huang, Wei; Frantzell, Arne; Toma, Jonathan; Petropoulos, Christos J.] Monogram Biosci Inc, Res & Dev, San Francisco, CA 94080 USA. [Napolitano, Laura; Coakley, Eoin] Monogram Biosci Inc, Clin Res, San Francisco, CA 94080 USA. [Whitcomb, Jeannette] Monogram Biosci Inc, Operat, San Francisco, CA 94080 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Haddad, M (reprint author), Monogram Biosci Inc, Bioinformat Biostat, San Francisco, CA 94080 USA. EM mhaddad@monogrambio.com OI Goetz, Matthew/0000-0003-4542-992X FU National Institutes of Health [U01 AI-42170, U01 AI-46362, U01 AI-68641] FX The authors would like to acknowledge the Monogram Biosciences clinical reference and R&D laboratories for performance of all phenotype and genotype assays. The CPCRA and INSIGHT networks are funded by the National Institutes of Health (U01 AI-42170, U01 AI-46362, U01 AI-68641). NR 32 TC 1 Z9 1 U1 0 U2 3 PU IMPERIAL COLLEGE PRESS PI LONDON PA 57 SHELTON ST, COVENT GARDEN, LONDON WC2H 9HE, ENGLAND SN 0219-7200 EI 1757-6334 J9 J BIOINF COMPUT BIOL JI J. Bioinform. Comput. Biol. PD AUG PY 2013 VL 11 IS 4 AR 1350006 DI 10.1142/S0219720013500066 PG 17 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA 268IO UT WOS:000328163800004 PM 23859270 ER PT J AU Morgan, AM Lo, J Fisher, DE AF Morgan, Ann M. Lo, Jennifer Fisher, David E. TI How does pheomelanin synthesis contribute to melanomagenesis? Two distinct mechanisms could explain the carcinogenicity of pheomelanin synthesis SO BIOESSAYS LA English DT Article DE melanoma; pheomelanin; pigmentation; reactive oxygen species ID OXYGEN PHOTOCONSUMPTION; TRANSIENT ABSORPTION; CELLS; MELANOGENESIS; PIGMENTATION; SPECTROSCOPY; GENERATION; EUMELANIN; EMISSION; REMOVAL AB Recently, we reported that melanoma risk in redheads is linked not only to pale skin, but also to the synthesis of the pigment - called pheomelanin - that gives red hair its color. We demonstrated that pheomelanin synthesis is associated with increased oxidative stress in the skin, yet we have not uncovered the chemical pathway between the molecule pheomelanin and the DNA damage that drives melanoma formation. Here, we hypothesize two possible pathways. On one hand, pheomelanin might generate reactive oxygen species (ROS) that directly or indirectly cause oxidative DNA damage. On the other hand, pheomelanin synthesis might consume cellular antioxidant stores and make the cell nucleus more vulnerable to other endogenous ROS. Uncovering the mechanistic pathway between pheomelanin and oxidative DNA damage will be an important step in developing strategies to lower melanoma risk in redheads. C1 [Morgan, Ann M.; Lo, Jennifer; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Morgan, AM (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. EM amorgan@college.harvard.edu FU NIAMS NIH HHS [R01 AR043369]; NIGMS NIH HHS [T32 GM007753] NR 25 TC 14 Z9 14 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 EI 1521-1878 J9 BIOESSAYS JI Bioessays PD AUG PY 2013 VL 35 IS 8 BP 672 EP 676 DI 10.1002/bies.201300020 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 262YR UT WOS:000327774300004 PM 23650156 ER PT J AU Ahmed, FA Kamnaksh, A Kovesdi, E Long, JB Agoston, DV AF Ahmed, Farid A. Kamnaksh, Alaa Kovesdi, Erzsebet Long, Joseph B. Agoston, Denes V. TI Long-term consequences of single and multiple mild blast exposure on select physiological parameters and blood-based biomarkers SO ELECTROPHORESIS LA English DT Article DE Animal models; Brain trauma; Experimental; Physiology; Proteomics ID TRAUMATIC BRAIN-INJURY; CONCUSSION; RATS AB Mild traumatic brain injury (mTBI), especially when it is repeated (rmTBI), can lead to progressive degenerative diseases and lasting neuropsychiatric abnormalities. To better understand the long-term pathobiological changes in mTBI and rmTBI, we exposed rats to single or repeated (5 total; administered on consecutive days) mild blast overpressure, monitored changes in physiological parameters, and determined the plasma levels of select biomarkers at 42 days post injury by proteomics. We unexpectedly found comparable changes in arterial oxygen saturation levels and heart rates of single-injured (SI) and multiple-injured (MI) rats throughout the observation period. Our analyses indicated lasting oxidative stress, vascular abnormalities, and neuronal and glial cell loss in both injured groups. However, MI rats exhibited a relatively more pronounced increase in the plasma levels of most of the tested markers-particularly those associated with inflammation-albeit the differences between the two injured groups were not statistically significant. Our findings indicate that the frequency of blast exposures is an important determinant of the resulting cumulative damage in rmTBI. C1 [Ahmed, Farid A.; Kamnaksh, Alaa; Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Ahmed, Farid A.; Kamnaksh, Alaa; Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Kovesdi, Erzsebet] US Dept Vet Affairs, Vet Affairs Cent Off, Washington, DC USA. [Long, Joseph B.] Walter Reed Army Inst Res, Blast Induced Neurotrauma Branch, Ctr Mil Psychiat & Neurosci, Silver Spring, MD USA. RP Agoston, DV (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vagoston@usuhs.edu FU Center for Neuroscience and Regenerative Medicine [G1703F] FX We thank the Neurotrauma Team at the Walter Reed Army Institute of Research for their technical help during the exposures. This work was supported by the Center for Neuroscience and Regenerative Medicine grant number G1703F. The views, opinions, and/or findings contained herein are those of the authors and should not be construed as an official position, policy, or decision of the Department of the Army or the Department of Defense. The authors have no financial disclosures. Animal handling and treatments were conducted in compliance with the Animal Welfare Act and other Federal statutes and regulations related to animals and experiments involving animals, and adhered to principles stated in the Guide to the Care and Use of Laboratory Animals, National Research Council. The facilities are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. NR 18 TC 13 Z9 14 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0173-0835 EI 1522-2683 J9 ELECTROPHORESIS JI Electrophoresis PD AUG PY 2013 VL 34 IS 15 BP 2229 EP 2233 DI 10.1002/elps.201300077 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 261KJ UT WOS:000327663600012 PM 23712899 ER PT J AU Buttenheim, AM Cherng, ST Asch, DA AF Buttenheim, Alison M. Cherng, Sarah T. Asch, David A. TI Provider dismissal policies and clustering of vaccine-hesitant families An agent-based modeling approach SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article DE vaccination; immunization; immunization schedule; decision-making; parents ID DISEASE OUTBREAKS; REFUSES VACCINES; DYNAMICS; BEHAVIOR; IMMUNIZATION; EPIDEMIOLOGY; EXPERIENCE; NETWORKS; CHILDREN; HEALTH AB Many pediatric practices have adopted vaccine policies that require parents who refuse to vaccinate according to the ACIP schedule to find another health care provider. Such policies may inadvertently cluster unvaccinated patients into practices that tolerate non-vaccination or alternative schedules, turning them into risky pockets of low herd immunity. The objective of this study was to assess the effect of provider zero-tolerance vaccination policies on the clustering of intentionally unvaccinated children. We developed an agent-based model of parental vaccine hesitancy, provider non-vaccination tolerance, and selection of patients into pediatric practices. We ran 84 experiments across a range of parental hesitancy and provider tolerance scenarios. When the model is initialized, all providers accommodate refusals and intentionally unvaccinated children are evenly distributed across providers. As provider tolerance decreases, hesitant children become more clustered in a smaller number of practices and eventually are not able to find a practice that will accept them. Each of these effects becomes more pronounced as the level of hesitancy in the population rises. Heterogeneity in practice tolerance to vaccine-hesitant parents has the unintended result of concentrating susceptible individuals within a small number of tolerant practices, while providing little if any compensatory protection to adherent individuals. These externalities suggest an agenda for stricter policy regulation of individual practice decisions. C1 [Buttenheim, Alison M.] Univ Penn, Sch Nursing, Dept Family & Community Hlth, Philadelphia, PA 19104 USA. [Buttenheim, Alison M.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Cherng, Sarah T.] Univ Michigan, Ctr Studies Complex Syst, Ann Arbor, MI 48109 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Buttenheim, AM (reprint author), Univ Penn, Sch Nursing, Dept Family & Community Hlth, Philadelphia, PA 19104 USA. EM abutt@nursing.upenn.edu OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation Health and Society Scholars Program at the University of Pennsylvania; National Cancer Institute [1KM1CA156715-01] FX This research was supported by the Robert Wood Johnson Foundation Health and Society Scholars Program at the University of Pennsylvania and by the National Cancer Institute (1KM1CA156715-01). NR 33 TC 7 Z9 7 U1 2 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD AUG 1 PY 2013 VL 9 IS 8 BP 1819 EP 1824 DI 10.4161/hv.25635 PG 6 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 259SY UT WOS:000327547800035 PM 23831786 ER PT J AU Zhou, JY Krovvidi, RK Gao, YQ Gao, H Petritis, BO De, AK Miller-Graziano, CL Bankey, PE Petyuk, VA Nicora, CD Clauss, TR Moore, RJ Shi, TJ Brown, JN Kaushal, A Xiao, WZ Davis, RW Maier, RV Tompkins, RG Qian, WJ Camp, DG Smith, RD AF Zhou, Jian-Ying Krovvidi, Ravi K. Gao, Yuqian Gao, Hong Petritis, Brianne O. De, Asit K. Miller-Graziano, Carol L. Bankey, Paul E. Petyuk, Vladislav A. Nicora, Carrie D. Clauss, Therese R. Moore, Ronald J. Shi, Tujin Brown, Joseph N. Kaushal, Amit Xiao, Wenzhong Davis, Ronald W. Maier, Ronald V. Tompkins, Ronald G. Qian, Wei-Jun Camp, David G., II Smith, Richard D. CA Inflammation Host Response Injury TI Trauma-associated human neutrophil alterations revealed by comparative proteomics profiling SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE Genomics; Human neutrophil; LC-MS; MS; Trauma ID NF-KAPPA-B; TANDEM MASS-SPECTROMETRY; INFLAMMATORY RESPONSE; SHOTGUN PROTEOMICS; CELL-PROLIFERATION; PROTEIN-SYNTHESIS; GENE-EXPRESSION; CANCER-CELLS; APOPTOSIS; ACTIVATION AB PurposePolymorphonuclear neutrophils (PMNs) play an important role in mediating the innate immune response after severe traumatic injury; however, the cellular proteome response to traumatic condition is still largely unknown. Experimental designWe applied 2D-LC-MS/MS-based shotgun proteomics to perform comparative proteome profiling of human PMNs from severe trauma patients and healthy controls. ResultsA total of 197 out of approximate to 2500 proteins (being identified with at least two peptides) were observed with significant abundance changes following the injury. The proteomics data were further compared with transcriptomics data for the same genes obtained from an independent patient cohort. The comparison showed that the protein abundance changes for the majority of proteins were consistent with the mRNA abundance changes in terms of directions of changes. Moreover, increased protein secretion was suggested as one of the mechanisms contributing to the observed discrepancy between protein and mRNA abundance changes. Functional analyses of the altered proteins showed that many of these proteins were involved in immune response, protein biosynthesis, protein transport, NRF2-mediated oxidative stress response, the ubiquitin-proteasome system, and apoptosis pathways. Conclusions and clinical relevanceOur data suggest increased neutrophil activation and inhibited neutrophil apoptosis in response to trauma. The study not only reveals an overall picture of functional neutrophil response to trauma at the proteome level, but also provides a rich proteomics data resource of trauma-associated changes in the neutrophil that will be valuable for further studies of the functions of individual proteins in PMNs. C1 [Zhou, Jian-Ying; Krovvidi, Ravi K.; Gao, Yuqian; Petritis, Brianne O.; Petyuk, Vladislav A.; Nicora, Carrie D.; Clauss, Therese R.; Moore, Ronald J.; Shi, Tujin; Brown, Joseph N.; Qian, Wei-Jun; Camp, David G., II; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Zhou, Jian-Ying; Krovvidi, Ravi K.; Gao, Yuqian; Petritis, Brianne O.; Petyuk, Vladislav A.; Nicora, Carrie D.; Clauss, Therese R.; Moore, Ronald J.; Shi, Tujin; Brown, Joseph N.; Qian, Wei-Jun; Camp, David G., II; Smith, Richard D.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. [De, Asit K.; Miller-Graziano, Carol L.; Bankey, Paul E.] Univ Rochester, Sch Med, Dept Surg, Rochester, NY USA. [Gao, Hong; Kaushal, Amit; Xiao, Wenzhong; Davis, Ronald W.] Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Xiao, Wenzhong; Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Tompkins, Ronald G.] Harvard Univ, Sch Med, Dept Surg, Shriners Burn Ctr, Boston, MA 02115 USA. [Tompkins, Ronald G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Smith, RD (reprint author), Pacific NW Natl Lab, Environm Mol Sci Lab, POB 999,MSIN K8-98, Richland, WA 99352 USA. EM rds@pnnl.gov RI Smith, Richard/J-3664-2012; Shi, Tujin/O-1789-2014; OI Smith, Richard/0000-0002-2381-2349; Baker, Henry/0000-0002-8273-5320; Petyuk, Vladislav/0000-0003-4076-151X FU NIH [U54 GM-62119-02, T32 GM-008256, P41 GM103493, DP2OD006668]; EMSL (Environmental Molecular Science Laboratory); US Department of Energy (DOE) Office of Biological and Environmental Research on the Pacific Northwest National Laboratory (PNNL) campus in Richland, Washington; DOE [DE-AC05-76RLO-1830] FX Portions of this research were supported by NIH grants U54 GM-62119-02 (to R.G.T.) and T32 GM-008256 (to R.G.T.), P41 GM103493 (to R.D.S.), DP2OD006668 (to W.J.Q.), and EMSL (Environmental Molecular Science Laboratory). EMSL is a national scientific user facility sponsored by the US Department of Energy (DOE) Office of Biological and Environmental Research on the Pacific Northwest National Laboratory (PNNL) campus in Richland, Washington. PNNL is operated by Battelle for the DOE under contract DE-AC05-76RLO-1830. NR 81 TC 4 Z9 4 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1862-8346 EI 1862-8354 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD AUG PY 2013 VL 7 IS 7-8 SI SI BP 571 EP 583 DI 10.1002/prca.201200109 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 263FQ UT WOS:000327792800011 PM 23589343 ER PT J AU Kashyap, SR Bhatt, DL Wolski, K Watanabe, RM Abdul-Ghani, M Abood, B Pothier, CE Brethauer, S Nissen, S Gupta, M Kirwan, JP Schauer, PR AF Kashyap, Sangeeta R. Bhatt, Deepak L. Wolski, Kathy Watanabe, Richard M. Abdul-Ghani, Muhammad Abood, Beth Pothier, Claire E. Brethauer, Stacy Nissen, Steven Gupta, Manjula Kirwan, John P. Schauer, Philip R. TI Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes Analysis of a randomized control trial comparing surgery with intensive medical treatment SO DIABETES CARE LA English DT Article ID GASTRIC BYPASS-SURGERY; BETA-CELL FUNCTION; LIFE-STYLE INTERVENTION; GLUCAGON-LIKE PEPTIDE-1; GLUCOSE-TOLERANCE; INSULIN-SECRETION; GLYCEMIC CONTROL; INCRETIN LEVELS; WEIGHT-LOSS; THERAPY AB OBJECTIVETo evaluate the effects of two bariatric procedures versus intensive medical therapy (IMT) on -cell function and body composition.RESEARCH DESIGN AND METHODSThis was a prospective, randomized, controlled trial of 60 subjects with uncontrolled type 2 diabetes (HbA(1c) 9.7 1%) and moderate obesity (BMI 36 2 kg/m(2)) randomized to IMT alone, IMT plus Roux-en-Y gastric bypass, or IMT plus sleeve gastrectomy. Assessment of -cell function (mixed-meal tolerance testing) and body composition was performed at baseline and 12 and 24 months.RESULTSGlycemic control improved in all three groups at 24 months (N = 54), with a mean HbA(1c) of 6.7 +/- 1.2% for gastric bypass, 7.1 +/- 0.8% for sleeve gastrectomy, and 8.4 +/- 2.3% for IMT (P < 0.05 for each surgical group versus IMT). Reduction in body fat was similar for both surgery groups, with greater absolute reduction in truncal fat in gastric bypass versus sleeve gastrectomy (-16 vs. -10%; P = 0.04). Insulin sensitivity increased significantly from baseline in gastric bypass (2.7-fold; P = 0.004) and did not change in sleeve gastrectomy or IMT. -Cell function (oral disposition index) increased 5.8-fold in gastric bypass from baseline, was markedly greater than IMT (P = 0.001), and was not different between sleeve gastrectomy versus IMT (P = 0.30). At 24 months, -cell function inversely correlated with truncal fat and prandial free fatty acid levels.CONCLUSIONSBariatric surgery provides durable glycemic control compared with intensive medical therapy at 2 years. Despite similar weight loss as sleeve gastrectomy, gastric bypass uniquely restores pancreatic -cell function and reduces truncal fat, thus reversing the core defects in diabetes. C1 [Kashyap, Sangeeta R.; Abood, Beth; Gupta, Manjula] Cleveland Clin, Endocrinol & Metab Inst, Cleveland, OH 44106 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. [Wolski, Kathy; Pothier, Claire E.; Nissen, Steven] Cleveland Clin, Miller Family Heart & Vasc Inst, Cleveland, OH 44106 USA. [Watanabe, Richard M.] Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. [Abdul-Ghani, Muhammad] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Brethauer, Stacy; Schauer, Philip R.] Cleveland Clin, Bariatr & Metab Inst, Cleveland, OH 44106 USA. [Kirwan, John P.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. RP Kashyap, SR (reprint author), Cleveland Clin, Endocrinol & Metab Inst, Cleveland, OH 44106 USA. EM kashyas@ccf.org FU Ethicon Endo-Surgery EES IIS [19900]; American Diabetes Association [1-11-26 CT]; National Institutes of Health [R01-DK089547]; Ethicon Endo-Surgery; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi; Medicines Company; FlowCo; Nestle Inc.; ScottCare; Bard-Davol; Stryker Endoscopy; Gore; Baxter; Covidien; Allergan FX Primary funding for the STAMPEDE trial is from Ethicon Endo-Surgery EES IIS 19900 (to P.R.S.). The American Diabetes Association clinical translational award (1-11-26 CT) to S.R.K. provided ancillary funding for STAMPEDE. A grant from the National Institutes of Health (R01-DK089547) to S.R.K., P.R.S., and J.P.K. was provided.; S.R.K. obtained research grants from Ethicon Endo-Surgery, National Institutes of Health, and American Diabetes Association. D.L.B. is a member of the Advisory Board for Medscape Cardiology, is on the Board of Directors for Boston VA Research Institute and Society of Chest Pain Centers, is the Chair of American Heart Association Get With The Guidelines Science Subcommittee, received honoraria from American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), and WebMD (CME steering committees), is the Senior Associate Editor of Journal of Invasive Cardiology, received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi, The Medicines Company, and FlowCo, and performed unfunded research for PLx Pharma and Takeda. D.L.B. receives honoraria from Ethicon Endo-Surgery as scientific advisory board member, consultant, and speaker, and has received honoraria from Covidien for speaking. J.P.K. receives grant funding from National Institutes of Health, Nestle Inc., and ScottCare. P.R.S. obtained research grants from Ethicon Endo-surgery, National Institutes of Health, and Bard-Davol; received educational grants from Stryker Endoscopy, Gore, Baxter, Covidien, and Allergan; and received honoraria from Ethicon Endo-surgery as a scientific advisory board member, consultant, and speaker. P.R.S. has been a consultant/advisory board member for RemedyMD, StrykerEndoscopy, Bard-Davol, Gore, Barosense, Surgiquest, and Carefusion. S.N. has consulted with Orexigen and Vivus. S.R.K., P.R.S., and the Cleveland Clinic Coordinating Center for Clinical Research had full and independent access to all of the data in the study. The sponsor participated in discussions regarding study design and protocol development and provided logistical support during the trial. The database, statistical analysis, and monitoring were all performed by the Cleveland Clinic Coordinating Center for Clinical Research. The manuscript was prepared by the corresponding author and modified after consultation with co-authors. The sponsor was permitted to review the manuscript and suggest changes, but the final decision on content and submission was exclusively retained by the academic authors. J. Michael Henderson, MD (Chair), James B. Young, MD, and Venu Menon, MD, Cleveland Clinic, Cleveland, Ohio, are members of the Data and Safety Monitoring Board. No other potential conflicts of interest relevant to this article were reported. NR 31 TC 102 Z9 105 U1 0 U2 18 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2013 VL 36 IS 8 BP 2175 EP 2182 DI 10.2337/dc12-1596 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255PP UT WOS:000327252600027 PM 23439632 ER PT J AU Strickland, LR Guo, FJ Lok, K Garvey, WT AF Strickland, Leah R. Guo, Fangjian Lok, Kerry Garvey, W. Timothy TI Type 2 Diabetes With Partial Lipodystrophy of the Limbs A new lipodystrophy phenotype SO DIABETES CARE LA English DT Article ID FAMILIAL PARTIAL LIPODYSTROPHY; LEPTIN-REPLACEMENT THERAPY; FATTY-ACID-METABOLISM; INSULIN-RESISTANCE; INHERITED LIPODYSTROPHIES; ADIPOSE-TISSUE; GLUCOSE-UPTAKE; BODY-FAT; MACROPHAGES; MICE AB OBJECTIVELipodystrophies are categorized by the extent of fat loss (generalized vs. partial) and by inheritance (congenital vs. acquired). We examined whether a group of patients with partial lipodystrophy of the limbs (PLL), type 2 diabetes mellitus (T2DM), and an absence of a family history of lipodystrophy constitute a new clinical subtype.RESEARCH DESIGN AND METHODSTen women with T2DM and PLL were identified in academic diabetes clinics and were matched by age, sex, BMI, ethnicity, and diabetes status with 10 women with control T2DM without lipodystrophy. All patients were characterized by clinical evaluation and hyperinsulinemic clamp.RESULTSPatients with T2DM and PLL exhibited symmetrical loss of subcutaneous fat in forearms, or forearms plus calves, and acanthosis nigricans. Maximally stimulated glucose disposal rates were markedly reduced by 56% in the T2DM with PLL group compared with the control T2DM patients, whether normalized by body weight or surface area. Most PLL patients exhibited little or no insulin-mediated glucose uptake after subtraction of non-insulin-mediated glucose uptake. The T2DM with PLL group also had greater elevations in hepatic transaminases and triglycerides and earlier onset of diabetes compared with control T2DM.CONCLUSIONST2DM with PLL represents a previously unrecognized phenotype of lipodystrophy and of T2DM. These T2DM patients exhibit symmetrical lipodystrophy of the distal limbs, acanthosis nigricans, marked insulin resistance with little insulin-mediated glucose uptake, hypertriglyceridemia, and hepatic transaminase elevations, which are greater in severity than observed in patients with common T2DM. C1 [Strickland, Leah R.; Guo, Fangjian; Lok, Kerry; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Strickland, Leah R.] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. EM garveyt@uab.edu RI Guo, Fangjian/B-7705-2015 OI Guo, Fangjian/0000-0003-3729-2724 FU National Institutes of Health [DK-083562, DK-038764]; Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases [P60-DK-079626]; Amylin Pharmaceuticals, Inc.; Merck Co.; UAB Obesity Training Program [T32 DK-062710] FX This work was supported by grants from the National Institutes of Health (DK-083562, DK-038764) to W.T.G, and the Merit Review program of the Department of Veterans Affairs to W.T.G. L.R.S. was supported by a Summer Research Fellowship for Medical Students provided by National Institute of Diabetes and Digestive and Kidney Diseases to the University of Alabama (UAB) Diabetes Research and Training Center (P60-DK-079626) and administered by the UAB Obesity Training Program (T32 DK-062710).; W.T.G. has received speaker honoraria from Merck & Co.; has served on advisory boards for Vivus, Daiichi-Sankyo, LipoScience, Janssen, and Alkermes; and has received research support from Amylin Pharmaceuticals, Inc. and Merck & Co. No other potential conflicts of interest relevant to this article were reported. NR 28 TC 8 Z9 10 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2013 VL 36 IS 8 BP 2247 EP 2253 DI 10.2337/dc12-1529 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255PP UT WOS:000327252600037 PM 23423695 ER PT J AU Nathan, DM Buse, JB Kahn, SE Krause-Steinrauf, H Larkin, ME Staten, M Wexler, D Lachin, JM AF Nathan, David M. Buse, John B. Kahn, Steven E. Krause-Steinrauf, Heidi Larkin, Mary E. Staten, Myrlene Wexler, Deborah Lachin, John M. CA GRADE Study Res Grp TI Rationale and Design of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; CARDIOVASCULAR-DISEASE; GLYBURIDE MONOTHERAPY; LIFE-STYLE; FOLLOW-UP; MELLITUS; METFORMIN; HYPERGLYCEMIA; ASSOCIATION; PREVENTION AB OBJECTIVEThe epidemic of type 2 diabetes (T2DM) threatens to become the major public health problem of this century. However, a comprehensive comparison of the long-term effects of medications to treat T2DM has not been conducted. GRADE, a pragmatic, unmasked clinical trial, aims to compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes.RESEARCH DESIGN AND METHODSGRADE was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The consensus protocol was approved by NIDDK and the GRADE Research Group. Eligibility criteria for the 5,000 metformin-treated subjects include <5 years' diabetes duration, 30 years of age at time of diagnosis, and baseline hemoglobin A(1c) (A1C) of 6.8-8.5% (51-69 mmol/mol). Medications representing four classes (sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and insulin) will be randomly assigned and added to metformin (minimum-maximum 1,000-2,000 mg/day). The primary metabolic outcome is the time to primary failure defined as an A1C 7% (53 mmol/mol), subsequently confirmed, over an anticipated mean observation period of 4.8 years (range 4-7 years). Other long-term metabolic outcomes include the need for the addition of basal insulin after a confirmed A1C >7.5% (58 mmol/mol) and, ultimately, the need to implement an intensive basal/bolus insulin regimen. The four drugs will also be compared with respect to selected microvascular complications, cardiovascular disease risk factors, adverse effects, tolerability, quality of life, and cost-effectiveness.CONCLUSIONSGRADE will compare the long-term effectiveness of major glycemia-lowering medications and provide guidance to clinicians about the most appropriate medications to treat T2DM. GRADE begins recruitment at 37 centers in the U.S. in 2013. C1 [Nathan, David M.; Larkin, Mary E.; Wexler, Deborah] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Nathan, David M.; Larkin, Mary E.; Wexler, Deborah] Harvard Univ, Sch Med, Boston, MA USA. [Buse, John B.] Univ N Carolina, Dept Med, Div Endocrinol, Chapel Hill, NC USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Krause-Steinrauf, Heidi; Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Staten, Myrlene] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. RP Krause-Steinrauf, H (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. EM heidi@bsc.gwu.edu OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 FU NIDDK, NIH [5U34-DK-088043-02]; American Diabetes Association; Abbott; Amylin; Andromeda; AstraZeneca; Bayhill Therapeutics; BD Research Laboratories; Boehringer Ingelheim; Bristol-Myers Squibb; Catabasis; Cebix; Diartis, Elcelyx; Eli Lilly; Exsulin; Genentech; GI Dynamics; GlaxoSmithKline; Halozyme; Hoffman-La Roche; Johnson Johnson; LipoScience; Medtronic; Merck; Metabolic Solutions Development Company; Metabolon; Novan; Novella; Novartis; Novo Nordisk; Orexigen; Osiris; Pfizer; Rhythm; Sanofi; Spherix; Takeda; Tolerex; TransPharma; Veritas; Verva; [1U01-DK-098246-01] FX The planning of GRADE was supported by a U34 planning grant from the NIDDK, NIH (5U34-DK-088043-02). The American Diabetes Association provided funds for the initial planning meeting for developing the U34 proposal. GRADE is supported by a U01 grant (1U01-DK-098246-01). Educational materials have been provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies has been provided by BD, Bristol-Myers Squibb, Merck, Novo Nordisk, Roche Diagnostics, and Sanofi.; J.B.B.'s employer (the University of North Carolina) has received payments for his work as a consultant or investigator from Abbott, Amylin, Andromeda, AstraZeneca, Bayhill Therapeutics, BD Research Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Catabasis, Cebix, Diartis, Elcelyx, Eli Lilly, Exsulin, Genentech, GI Dynamics, GlaxoSmithKline, Halozyme, Hoffman-La Roche, Johnson & Johnson, LipoScience, Medtronic, Merck, Metabolic Solutions Development Company, Metabolon, Novan, Novella, Novartis, Novo Nordisk, Orexigen, Osiris, Pfizer, Rhythm, Sanofi, Spherix, Takeda, Tolerex, TransPharma, Veritas, and Verva. S.E.K. has received honoraria for consulting from Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Intarcia Therapeutics, Janssen, Merck, Novo Nordisk, and Receptos and honoraria for speaking from Boehringer Ingelheim and Merck. J.M.L. has received honoraria for consulting from Merck, Boehringer Ingelheim, Eli Lilly, Novartis, and Janssen. No other potential conflicts of interest relevant to this article were reported. NR 40 TC 61 Z9 61 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2013 VL 36 IS 8 BP 2254 EP 2261 DI 10.2337/dc13-0356 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255PP UT WOS:000327252600038 PM 23690531 ER PT J AU Lopes-Virella, MF Baker, NL Hunt, KJ Cleary, PA Klein, R Virella, G AF Lopes-Virella, Maria F. Baker, Nathaniel L. Hunt, Kelly J. Cleary, Patricia A. Klein, Richard Virella, Gabriel CA DCCT EDIC Res Grp TI Baseline Markers of Inflammation Are Associated With Progression to Macroalbuminuria in Type 1 Diabetic Subjects SO DIABETES CARE LA English DT Article ID EURODIAB PROSPECTIVE COMPLICATIONS; TNF RECEPTORS 1; RISK-FACTORS; MICROVASCULAR COMPLICATIONS; MACROVASCULAR COMPLICATIONS; ENDOTHELIAL DYSFUNCTION; VASCULAR-DISEASE; DCCT/EDIC COHORT; FOLLOW-UP; NEPHROPATHY AB OBJECTIVEThe current study aimed to determine in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort whether or not abnormal levels of markers of inflammation and endothelial dysfunction measured in samples collected at DCCT baseline were able to predict the development of macroalbuminuria.RESEARCH DESIGN AND METHODSLevels of inflammation and endothelial cell dysfunction biomarkers were measured in 1,237 of 1,441 patients enrolled in the DCCT study who were both free of albuminuria and cardiovascular disease at baseline. To test the association of log-transformed biomarkers with albuminuria, generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, micro-, and macroalbuminuria were the outcomes of interest.RESULTSIn the logistic regression models adjusted by DCCT treatment assignment, baseline albumin excretion rate, and use of ACE/angiotensin receptor blocker drugs, one unit increase in the standardized levels of soluble E-selectin (sE-selectin) was associated with an 87% increase in the odds to develop macroalbuminuria and one unit increase in the levels of interleukin-6 (IL-6), plasminogen activator inhibitor 1 (PAI-1; total and active), and soluble tumor necrosis factor receptors (TNFR)-1 and -2 lead to a 30-50% increase in the odds to develop macroalbuminuria. Following adjustment for DCCT baseline retinopathy status, age, sex, HbA(1c), and duration of diabetes, significant associations remained for sE-selectin and TNFR-1 and -2 but not for IL-6 or PAI-1.CONCLUSIONSOur study indicates that high levels of inflammatory markers, mainly E-selectin and sTNRF-1 and -2, are important predictors of macroalbuminuria in patients with type 1 diabetes. C1 [Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.; Klein, Richard] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Baker, Nathaniel L.; Hunt, Kelly J.] Med Univ S Carolina, Dept Publ Hlth Serv, Charleston, SC 29425 USA. [Cleary, Patricia A.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC 29425 USA. EM virellam@musc.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center; Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the National Institutes of Health; National Center for Research Resources through the General Clinical Research Centers program; Genentech, Inc.; [R01-DK-081352] FX This work was supported by the Grant R01-DK-081352 funded by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center.; The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the National Institutes of Health. Additional support was provided by the National Center for Research Resources through the General Clinical Research Centers program and by Genentech, Inc., through a Cooperative Research and Development Agreement with the NIDDK. No other potential conflicts of interest relevant to this article were reported. NR 27 TC 27 Z9 27 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2013 VL 36 IS 8 BP 2317 EP 2323 DI 10.2337/dc12-2521 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255PP UT WOS:000327252600047 PM 23514730 ER PT J AU Chirinos, JA Segers, P Gillebert, TC Buyzere, ML Van Daele, CM Khan, ZA Khawar, U Bacquer, D Rietzschel, ER AF Chirinos, Julio A. Segers, Patrick Gillebert, Thierry C. De Buyzere, Marc L. Van Daele, Caroline M. Khan, Zubair A. Khawar, Umair De Bacquer, Dirk Rietzschel, Ernst R. CA Asklepios Investigators TI Central Pulse Pressure and Its Hemodynamic Determinants in Middle-Aged Adults With Impaired Fasting Glucose and Diabetes SO DIABETES CARE LA English DT Article ID AORTIC ROOT DILATATION; CARDIOVASCULAR RISK-FACTORS; BODY-SURFACE AREA; ARTERIAL STIFFNESS; NONINVASIVE EVALUATION; ESSENTIAL-HYPERTENSION; WAVE REFLECTIONS; PLASMA-GLUCOSE; ORGAN DAMAGE; OLDER-ADULTS AB OBJECTIVEPulse pressure (PP), a strong predictor of cardiovascular events in type 2 diabetes, is a composite measure affected by several hemodynamic factors. Little is known about the hemodynamic determinants of central PP in type 2 diabetes or whether abnormalities in central pulsatile hemodynamics are already present in individuals with impaired fasting glucose (IFG). In a population-based study, we aimed to compare central PP and its hemodynamic determinants among adults with normal fasting glucose (n = 1654), IFG (n = 240), and type 2 diabetes (n = 33).RESEARCH DESIGN AND METHODSWe measured carotid pressure, left ventricular outflow, aortic root diameter, carotid artery flow, and distension in order to measure various structural and hemodynamic arterial parameters.RESULTSIFG was associated with a greater mean arterial pressure (MAP) but was not associated with intrinsic aortic stiffening or abnormal aortic pulsatile indices after adjustment for MAP. After adjustment for age, sex, and MAP, type 2 diabetes was associated with a higher aortic root characteristic impedance (Zc), aortic root elastance-thickness product (Eh), and aortic root pulse wave velocity (but not aortic root diameter), a greater carotid-femoral pulse wave velocity, and lower total arterial compliance and wave reflection magnitude. Carotid size, Zc, distensibility, or Eh did not significantly differ between the groups.CONCLUSIONSType 2 diabetes, but not IFG, is associated with greater large artery stiffness, without abnormalities in aortic root diameter or carotid stiffness. Subjects with type 2 diabetes demonstrate a decreased reflection magnitude, which may indicate an increased penetration of pulsatile energy to distal vascular beds. C1 [Chirinos, Julio A.; Khan, Zubair A.; Khawar, Umair] Univ Penn, Sch Med, Hosp Univ Penn, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Segers, Patrick] Univ Ghent, Inst Biomed Technol, B-9000 Ghent, Belgium. [Gillebert, Thierry C.; De Buyzere, Marc L.; Van Daele, Caroline M.; Rietzschel, Ernst R.] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium. [De Bacquer, Dirk; Rietzschel, Ernst R.] Univ Ghent, Dept Publ Hlth, B-9000 Ghent, Belgium. RP Chirinos, JA (reprint author), Univ Penn, Sch Med, Hosp Univ Penn, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu OI Khan, Zubair/0000-0002-0451-9155; Gillebert, Thierry/0000-0002-3832-919X FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen Grant [G.0.838.10]; American Heart Association [0885031N]; National Institutes of Health; Atcor Medical; Cardiodynamics; APC Cardiovascular Ltd. FX This study was supported by Fonds voor Wetenschappelijk Onderzoek Vlaanderen Grant G.0.838.10 and the American Heart Association Research Award 0885031N. J.A.C. received significant (>$10,000) grants from the National Institutes of Health and the American Heart Association for research studies related to arterial hemodynamics and has received minor support (equipment loans) from Atcor Medical, Cardiodynamics, and APC Cardiovascular Ltd. No other potential conflicts of interest relevant to this article were reported. NR 41 TC 17 Z9 19 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2013 VL 36 IS 8 BP 2359 EP 2365 DI 10.2337/dc12-1463 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255PP UT WOS:000327252600053 PM 23610081 ER PT J AU Hill, JO Galloway, JM Goley, A Marrero, DG Minners, R Montgomery, B Peterson, GE Ratner, RE Sanchez, E Aroda, VR AF Hill, James O. Galloway, James M. Goley, April Marrero, David G. Minners, Regan Montgomery, Brenda Peterson, Gregory E. Ratner, Robert E. Sanchez, Eduardo Aroda, Vanita R. TI Scientific Statement: Socioecological Determinants of Prediabetes and Type 2 Diabetes SO DIABETES CARE LA English DT Article ID POSTCHALLENGE PLASMA-GLUCOSE; SUGAR-SWEETENED BEVERAGES; SCHOOL-BASED INTERVENTION; TELEVISION VIEWING TIME; LIFE-STYLE INTERVENTION; ALL-CAUSE MORTALITY; PHYSICAL-ACTIVITY; BUILT ENVIRONMENT; SEDENTARY TIME; SITTING TIME C1 [Hill, James O.] Univ Colorado, Sch Med, Denver, CO USA. [Galloway, James M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Goley, April] Univ N Carolina, Sch Med, Div Endocrinol, Chapel Hill, NC USA. [Marrero, David G.] Indiana Univ, Indianapolis, IN 46204 USA. [Minners, Regan; Ratner, Robert E.] Amer Diabet Assoc, Sci & Med Div, Alexandria, VA USA. [Montgomery, Brenda] Univ Washington, Seattle, WA 98195 USA. [Montgomery, Brenda] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Peterson, Gregory E.] Des Moines Univ, Des Moines, IA USA. [Sanchez, Eduardo] Amer Heart Assoc, Natl Ctr, Dallas, TX USA. [Aroda, Vanita R.] Georgetown Univ, Sch Med, MedStar Hlth Res Inst, Washington, DC USA. RP Ratner, RE (reprint author), Amer Diabet Assoc, Sci & Med Div, Alexandria, VA USA. EM rratner@diabetes.org NR 121 TC 28 Z9 28 U1 7 U2 20 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2013 VL 36 IS 8 BP 2430 EP 2439 DI 10.2337/dc13-1161 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255PP UT WOS:000327252600063 PM 23788649 ER PT J AU Beverly, EA Weinger, K AF Beverly, Elizabeth A. Weinger, Katie TI Response to Comment on: Beverly et al. Do Older Adults Aged 60-75 Years Benefit From Diabetes Behavioral Interventions? Diabetes Care 2013;36:1501-1506 SO DIABETES CARE LA English DT Letter ID EDUCATION C1 [Beverly, Elizabeth A.] Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2013 VL 36 IS 8 BP E126 EP E126 DI 10.2337/dc13-0723 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255PP UT WOS:000327252600011 PM 23881979 ER PT J AU Dougherty, DD AF Dougherty, Darin D. TI This issue: Deep Brain Stimulation SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Neurotherapeut Div, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Psychiat Neuroimaging Grp, Mood Disorders Sect, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Psychiat Neuroimaging Grp, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Obsess Compuls Disorder Inst, Boston, MA 02114 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Trichotillomania Clinic, Boston, MA 02114 USA. [Dougherty, Darin D.] Harvard Univ, Sch Med, MIT, Hlth Sci & Technol Clin Investigator Training Pro, Cambridge, MA 02138 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Neurotherapeut Div, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2013 VL 43 IS 8 BP 348 EP 349 DI 10.3928/00485713-20130806-02 PG 2 WC Psychiatry SC Psychiatry GA 256MF UT WOS:000327314100002 ER PT J AU Corse, AK Chou, T Arulpragasam, AR Kaur, N Deckersbach, T Cusin, C AF Corse, Andrew K. Chou, Tina Arulpragasam, Amanda R. Kaur, Navneet Deckersbach, Thilo Cusin, Cristina TI Deep Brain Stimulation for Obsessive-Compulsive Disorder SO PSYCHIATRIC ANNALS LA English DT Article ID SUBTHALAMIC NUCLEUS STIMULATION; ELECTRICAL-STIMULATION; CAPSULAR STIMULATION; PARKINSONS-DISEASE; ACCUMBENS; OUTCOMES; TRIAL C1 [Corse, Andrew K.; Chou, Tina; Arulpragasam, Amanda R.; Kaur, Navneet; Deckersbach, Thilo; Cusin, Cristina] Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, Boston, MA 02114 USA. [Chou, Tina] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Deckersbach, Thilo; Cusin, Cristina] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Cusin, Cristina] Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Sch Med,Dept Psychiat, Cambridge, MA 02138 USA. RP Cusin, C (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,Suite 634, Boston, MA 02114 USA. EM ccusin@partners.org NR 29 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2013 VL 43 IS 8 BP 351 EP 357 DI 10.3928/00485713-20130806-03 PG 7 WC Psychiatry SC Psychiatry GA 256MF UT WOS:000327314100003 ER PT J AU Kaur, N Chou, T Corse, AK Arulpragasam, AR Deckersbach, T Evans, KC AF Kaur, Navneet Chou, Tina Corse, Andrew K. Arulpragasam, Amanda R. Deckersbach, Thilo Evans, Karleyton C. TI Deep Brain Stimulation for Treatment-Resistant Depression SO PSYCHIATRIC ANNALS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; REFRACTORY MAJOR DEPRESSION; NUCLEUS-ACCUMBENS; DEFINITION; DIAGNOSIS; CIRCUITS; HABENULA C1 [Kaur, Navneet; Chou, Tina; Corse, Andrew K.; Arulpragasam, Amanda R.; Deckersbach, Thilo; Evans, Karleyton C.] Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, Charlestown, MA 02129 USA. [Chou, Tina] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Deckersbach, Thilo; Evans, Karleyton C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Evans, KC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY2625,149 13th St, Charlestown, MA 02129 USA. EM kcevans@partners.org NR 35 TC 0 Z9 0 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2013 VL 43 IS 8 BP 358 EP 365 DI 10.3928/00485713-20130806-04 PG 8 WC Psychiatry SC Psychiatry GA 256MF UT WOS:000327314100004 ER PT J AU Arulpragasam, AR Chou, T Kaur, N Corse, AK Deckersbach, T Camprodon, JA AF Arulpragasam, Amanda R. Chou, Tina Kaur, Navneet Corse, Andrew K. Deckersbach, Thilo Camprodon, Joan A. TI Future Directions of Deep Brain Stimulation: Current Disorders, New Technologies SO PSYCHIATRIC ANNALS LA English DT Article ID NUCLEUS-ACCUMBENS; TOURETTES-SYNDROME; ALZHEIMERS-DISEASE; COCAINE; RATS; CIRCUITS; SEEKING; OBESITY; MODELS; TICS C1 [Arulpragasam, Amanda R.; Chou, Tina; Kaur, Navneet; Corse, Andrew K.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut, Charlestown, MA 02129 USA. [Chou, Tina] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Deckersbach, Thilo] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Camprodon, Joan A.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Div Neurotherapeut,Sch Med, Cambridge, MA 02138 USA. [Camprodon, Joan A.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Lab Neuropsychiat & Neuromodulat,Sch Med, Cambridge, MA 02138 USA. RP Camprodon, JA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Lab Neuropsychiat & Neuromodulat, CNY2654,149 13th St, Charlestown, MA 02129 USA. EM camprodon.joan@mgh.harvard.edu NR 33 TC 0 Z9 0 U1 1 U2 8 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2013 VL 43 IS 8 BP 366 EP 373 DI 10.3928/00485713-20130806-05 PG 8 WC Psychiatry SC Psychiatry GA 256MF UT WOS:000327314100005 ER PT J AU Oliva, EM Bowe, T Harris, AHS Trafton, JA AF Oliva, Elizabeth M. Bowe, Thomas Harris, Alex H. S. Trafton, Jodie A. TI Datapoints False Starts in Psychotherapy for Substance Use Disorders and PTSD in the VHA SO PSYCHIATRIC SERVICES LA English DT Editorial Material C1 [Oliva, Elizabeth M.; Bowe, Thomas; Harris, Alex H. S.; Trafton, Jodie A.] US Dept Vet Affairs, Program Evaluat & Resource Ctr, Palo Alto Hlth Care Syst, Menlo Pk, CA 94025 USA. RP Oliva, EM (reprint author), US Dept Vet Affairs, Program Evaluat & Resource Ctr, Palo Alto Hlth Care Syst, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM elizabeth.oliva@va.gov NR 1 TC 2 Z9 2 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD AUG PY 2013 VL 64 IS 8 BP 722 EP 722 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255YN UT WOS:000327276100006 PM 23903602 ER PT J AU Gorrindo, T Goldfarb, E Chevalier, L Hoeppner, BB Birnbaum, RJ Meller, B Alpert, JE Herman, J Weiss, AP AF Gorrindo, Tristan Goldfarb, Elizabeth Chevalier, Lydia Hoeppner, Bettina B. Birnbaum, Robert J. Meller, Benjamin Alpert, Jonathan E. Herman, John Weiss, Anthony P. TI Interprofessional Differences in Disposition Decisions: Results From a Standardized Web-Based Patient Assessment SO PSYCHIATRIC SERVICES LA English DT Article ID PSYCHIATRIC EMERGENCY SERVICE; INTERRATER AGREEMENT; HOSPITALIZATION; DETERMINANTS AB Objective: This study examined differences in disposition decisions among mental health professionals using a standardized Web-based simulation. Methods: Using a Web-based simulation that described, across users, the same complex psychiatric patient, credentialed clinicians in a psychiatry department conducted a violence risk assessment and selected a level of follow-up care. Results: Of 410 clinicians who completed the simulation, 60% of psychiatrists were more likely than other types of clinicians to select higher levels of care (inpatient or emergency services) for the standardized virtual patient (odds ratio=2.67, 95% confidence interval=1.67-4.25), even after adjustment for other factors. Virtual actions taken, such as contracting with the patient for safety and discussing hospitalization, elucidated these training differences. Conclusions: Training backgrounds were important determinants of clinicians' actions and the dispositions they recommended for a psychiatric patient at high risk of self-harm and harm to others in the educational setting and may suggest the need for further training to standardize and optimize care. C1 [Gorrindo, Tristan; Goldfarb, Elizabeth; Chevalier, Lydia; Birnbaum, Robert J.; Meller, Benjamin; Alpert, Jonathan E.; Herman, John; Weiss, Anthony P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hoeppner, Bettina B.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Gorrindo, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Suite 700, Boston, MA 02114 USA. EM tristan.gorrindo@mgh.harvard.edu OI Alpert, Jonathan/0000-0002-4332-908X FU NIDA NIH HHS [K01 DA027097] NR 13 TC 3 Z9 3 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD AUG PY 2013 VL 64 IS 8 BP 808 EP 811 DI 10.1176/appi.ps.201200461 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255YN UT WOS:000327276100021 PM 23903607 ER PT J AU Kowalczyk, KJ Choueiri, TK Hevelone, ND Trinh, QD Lipsitz, SR Nguyen, PL Lynch, JH Hu, JC AF Kowalczyk, Keith J. Choueiri, Toni K. Hevelone, Nathanael D. Quoc-Dien Trinh Lipsitz, Stuart R. Nguyen, Paul L. Lynch, John H. Hu, Jim C. TI Comparative effectiveness, costs and trends in treatment of small renal masses from 2005 to 2007 SO BJU INTERNATIONAL LA English DT Article DE ablation; complications; kidney cancer; nephron-sparing surgery; renal insufficiency; small renal masses; SEER ID CHRONIC KIDNEY-DISEASE; LAPAROSCOPIC PARTIAL NEPHRECTOMY; INITIAL CASE-REPORT; RADICAL NEPHRECTOMY; CELL CARCINOMA; CANCER; MORBIDITY; MORTALITY; OUTCOMES AB Objective To perform a comprehensive analysis of the outcomes and costs for treatments for small renal masses (SRM) using a population-based approach. Partial nephrectomy may be associated with improved survival, although level-one evidence has questioned this survival advantage. Patients and Methods Using Surveillance, Epidemiology and End Results-Medicare data, we identified 1682 subjects who were diagnosed with SRM from 2005 to 2007. Treatment included open radical nephrectomy (ORN; n = 404), minimally-invasive radical nephrectomy (MIRN; n = 535), open partial nephrectomy (OPN; n = 330), minimally-invasive partial nephrectomy (MIPN; n = 160), ablation (n = 211) and surveillance (n = 42). Postoperative complications, renal insufficiency diagnosis, overall mortality, cancer-specific mortality and postoperative costs were compared. Covariates were balanced before outcomes analysis using propensity score methods. Results Although the use of nephron-sparing surgery (NSS) increased over the study period, radical nephrectomy remained the predominant approach for SRM in 2007. Minimally-invasive approaches had shorter lengths of stay (P < 0.001), whereas open approaches had more overall complications, respiratory complications and intensive care unit admissions (all P < 0.003). MIRN and ORN were associated with more peri-operative medical complications, acute renal failure, haemodialysis use and long-term chronic renal insufficiency diagnosis vs NSS (all P < 0.001). Ablation, MIRN and ORN were associated with the highest overall mortality rates (P < 0.001), whereas MIRN and ORN were associated with the highest cancer-specific mortality rates (P < 0.001). Treatment costs were lowest for surveillance ($2911) followed by ablation ($10730), MIRN ($15373), MIPN ($15695), OPN ($16986) and ORN ($17803). Conclusions Although not the predominant treatment approach for SRM over the study period, the use of NSS increased and was associated with improved survival, fewer complications and less renal insufficiency. Minimally-invasive approaches confer lower costs. C1 [Kowalczyk, Keith J.; Lynch, John H.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Lank Ctr Genitourinary Oncol, Boston, MA USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Hevelone, Nathanael D.; Lipsitz, Stuart R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Quoc-Dien Trinh] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. RP Kowalczyk, KJ (reprint author), Georgetown Univ Hosp, Dept Urol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM keith.kowalczyk@gunet.georgetown.edu OI Hevelone, Nathanael/0000-0003-4740-2085 FU Department of Defense Physician Training Award [W81XWH-08-1-0283] FX Jim C. Hu receives salary support from Department of Defense Physician Training Award W81XWH-08-1-0283. NR 32 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD AUG PY 2013 VL 112 IS 4 BP E273 EP E280 DI 10.1111/j.1464-410X.2012.11776.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 255CZ UT WOS:000327218200015 PM 23452093 ER PT J AU Brown, EN Purdon, PL AF Brown, Emery N. Purdon, Patrick L. TI The aging brain and anesthesia SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Review DE anesthesia; delirium; electroencephalogram; functional imaging; normal aging; postoperative cognitive dysfunction ID POSTOPERATIVE DELIRIUM; COGNITIVE DECLINE; ALZHEIMERS-DISEASE; GENERAL-ANESTHESIA; BURST SUPPRESSION; OXIDATIVE STRESS; NORMAL ADULTS; PROPOFOL; ISOFLURANE; HYPOTHESIS AB Purpose of reviewTo review the neurophysiology and neuroanatomy of normal aging and the recent recommendations for the clinical management of general anesthesia and sedation in the elderly.Recent findingsAs the population ages, the number of elderly patients having surgery is likewise increasing and with it, the prevalence of postoperative cognitive disorders. Postoperative cognitive disorders including delirium and postoperative cognitive dysfunction are common postanesthesia complications in elderly patients. Several risk factors for postoperative disorders have been identified, and anesthesiologists commonly adapt their practice habits when taking care of elderly patients to try to mitigate the effects of the anesthetics on postoperative cognitive function. These practices are reasonable and prudent; yet, they are not well supported by an understanding of the aging brain and specifics of how the anesthetic effects on the brain change with age. Through functional imaging and electrophysiological studies, much is being learned about the neurophysiology and the neuroanatomy of normal aging.SummaryOur analysis suggests that understanding the neurophysiology and neuroanatomy should be part of the standard working knowledge of anesthesiologists and that this knowledge can guide their use of the electroencephalogram to track more accurately the brain states of elderly patients receiving anesthesia care. C1 [Brown, Emery N.; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, GRB 444,55 Fruit St, Boston, MA 02114 USA. EM enb@neurostat.mit.edu FU National Institutes of Health (NIH) [DP1-OD003646, R01 GM104948-01, R01-MH071847, DP2-OD006454, K25-NS057580]; Massachusetts General Hospital Department of Anesthesia, Critical Care, and Pain Medicine; [R01-EB006385] FX This research was supported by a National Institutes of Health (NIH) Director's Pioneer Award DP1-OD003646, an NIH Director's Transformative Research Award R01 GM104948-01 and NIH Grant R01-MH071847 (to E.N.B.), by NIH New Innovator Award DP2-OD006454 and K-Award K25-NS057580 (to P. L. P.) and by R01-EB006385 (to E.N.B., P. L. P. and K. F. K. W.). This work was also supported by the Massachusetts General Hospital Department of Anesthesia, Critical Care, and Pain Medicine. NR 47 TC 11 Z9 13 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD AUG PY 2013 VL 26 IS 4 BP 414 EP 419 DI 10.1097/ACO.0b013e328362d183 PG 6 WC Anesthesiology SC Anesthesiology GA 253LS UT WOS:000327088700004 PM 23820102 ER PT J AU Coaker, H Bradner, JE AF Coaker, Hannah Bradner, James E. TI Interview with James Bradner SO FUTURE MEDICINAL CHEMISTRY LA English DT Editorial Material AB James E Bradner is an Assistant Professor in Medicine at Harvard Medical School (MA, USA) as well as a Staff Physician in the Division of Hematologic Malignancies at Dana-Farber Cancer Institute (MA, USA). The present research focus of the Bradner laboratory concerns the discovery and optimization of prototype drugs targeting cancer gene regulation. The clinical objective of the Bradner group is to deliver novel therapeutics for human clinical investigation in hematologic diseases. Bradner's awards and honors include the Damon Runyon-Rachleff Innovation Award, the Smith Family Award for Excellence in Biomedical Research, the Dunkin' Donuts Rising Star Award and the HMS Distinguished Excellence in Teaching Award. He is a member of the American Society of Clinical Investigation, the American Society of Hematology, the American Chemical Society and the American Association of Cancer Research. His recent research has been published in Nature, Cell, Nature Chemical Biology and the Journal of the American Chemical Society. He has authored more than 20 US Patent applications, licensed to five pharmaceutical companies, and is a scientific founder of Acetylon Pharmaceuticals, SHAPE Pharmaceuticals, Tensha Therapeutics and Syros Pharmaceuticals. Bradner received his AB from Harvard University, his MD from the University of Chicago (IL, USA) and a MMS from Harvard Medical School. He completed his postgraduate training in Internal Medicine at Brigham & Women's Hospital (MA, USA), followed by a fellowship in Medical Oncology and Hematology at Dana-Farber Cancer Institute. Following additional post-doctoral training in Chemistry at Harvard University and the Broad Institute (MA, USA) with Professor Stuart Schreiber, Bradner joined the research faculty of Dana-Farber in 2008. Interview conducted by Hannah Coaker, Assistant Commissioning Editor. C1 [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu NR 0 TC 2 Z9 2 U1 2 U2 6 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PD AUG PY 2013 VL 5 IS 12 BP 1373 EP 1376 DI 10.4155/fmc.13.124 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 254TC UT WOS:000327188900007 ER PT J AU Yoon, TJ Shao, HL Weissleder, R Lee, H AF Yoon, Tae-Jong Shao, Huilin Weissleder, Ralph Lee, Hakho TI Oxidation Kinetics and Magnetic Properties of Elemental Iron Nanoparticles SO PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION LA English DT Article DE iron nanoparticles; magnetism; nanoparticles; oxidation ID CORE-SHELL NANOPARTICLES; MONODISPERSE FE NANOPARTICLES; OXIDE FILM GROWTH; PARTICLES; NANOCRYSTALS; THERAPY C1 [Yoon, Tae-Jong] CHA Univ, Dept Appl Biosci, Seoul 135081, South Korea. [Shao, Huilin; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Yoon, TJ (reprint author), CHA Univ, Dept Appl Biosci, Seoul 135081, South Korea. EM hlee@mgh.harvard.edu FU B.S.-Ph.D. National Science Scholarship; Agency for Science, Technology and Research, Singapore; NIH [R01HL113156, R01EB004626, HHSN268201000044C, U54-CA151844] FX H.S. acknowledges financial support from the B.S.-Ph.D. National Science Scholarship awarded by the Agency for Science, Technology and Research, Singapore. This work was supported in part by NIH Grants (R01HL113156, R01EB004626, HHSN268201000044C, and U54-CA151844). NR 33 TC 3 Z9 3 U1 2 U2 21 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0934-0866 EI 1521-4117 J9 PART PART SYST CHAR JI Part. Part. Syst. Charact. PD AUG PY 2013 VL 30 IS 8 BP 667 EP 671 DI 10.1002/ppsc.201300013 PG 5 WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 255OT UT WOS:000327250400006 PM 24077230 ER PT J AU Wanderer, JP Charnin, J Driscoll, WD Bailin, MT Baker, K AF Wanderer, Jonathan P. Charnin, Jonathan Driscoll, William D. Bailin, Michael T. Baker, Keith TI Decision Support Using Anesthesia Information Management System Records and Accreditation Council for Graduate Medical Education Case Logs for Resident Operating Room Assignments SO ANESTHESIA AND ANALGESIA LA English DT Article AB Our goal in this study was to develop decision support systems for resident operating room (OR) assignments using anesthesia information management system (AIMS) records and Accreditation Council for Graduate Medical Education (ACGME) case logs and evaluate the implementations. We developed 2 Web-based systems: an ACGME case-log visualization tool, and Residents Helping in Navigating OR Scheduling (Rhinos), an interactive system that solicits OR assignment requests from residents and creates resident profiles. Resident profiles are snapshots of the cases and procedures each resident has done and were derived from AIMS records and ACGME case logs. A Rhinos pilot was performed for 6 weeks on 2 clinical services. One hundred sixty-five requests were entered and used in OR assignment decisions by a single attending anesthesiologist. Each request consisted of a rank ordered list of up to 3 ORs. Residents had access to detailed information about these cases including surgeon and patient name, age, procedure type, and admission status. Success rates at matching resident requests were determined by comparing requests with AIMS records. Of the 165 requests, 87 first-choice matches (52.7%), 27 second-choice matches (16.4%), and 8 third-choice matches (4.8%) were made. Forty-three requests were unmatched (26.1%). Thirty-nine first-choice requests overlapped (23.6%). Full implementation followed on 8 clinical services for 8 weeks. Seven hundred fifty-four requests were reviewed by 15 attending anesthesiologists, with 339 first-choice matches (45.0%), 122 second-choice matches (16.2%), 55 third-choice matches (7.3%), and 238 unmatched (31.5%). There were 279 overlapping first-choice requests (37.0%). The overall combined match success rate was 69.4%. Separately, we developed an ACGME case-log visualization tool that allows individual resident experiences to be compared against case minimums as well as resident peer groups. We conclude that it is feasible to use ACGME case-log data in decision support systems for informing resident OR assignments. Additional analysis will be necessary to assess the educational impact of these systems. C1 [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Anesthesiol, Nashville, TN 37235 USA. [Charnin, Jonathan; Driscoll, William D.; Baker, Keith] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Driscoll, William D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bailin, Michael T.] Baystate Med Ctr, Dept Anesthesiol, Springfield, MA USA. RP Wanderer, JP (reprint author), Vanderbilt Clin, Dept Anesthesiol, 1301 Med Ctr Dr,Suite 4648, Nashville, TN 37212 USA. EM jonathan.p.wanderer@vanderbilt.edu NR 6 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 2013 VL 117 IS 2 BP 494 EP 499 DI 10.1213/ANE.0b013e318294fb64 PG 6 WC Anesthesiology SC Anesthesiology GA 246BO UT WOS:000326511500029 PM 23749442 ER PT J AU Guyer, AC Long, AA AF Guyer, Autumn Chandler Long, Aidan Angelo TI Long-acting anticholinergics in the treatment of asthma SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE anticholinergics; asthma; ipratropium bromide; severe asthma; tiotropium bromide ID OBSTRUCTIVE PULMONARY-DISEASE; UNCONTROLLED ASTHMA; TIOTROPIUM BROMIDE; LUNG-FUNCTION; THERAPY; SALMETEROL; FLUTICASONE; PHENOTYPE; COPD; EXACERBATIONS AB Purpose of reviewThe use of anticholinergic medications is well established as maintenance therapy for chronic obstructive pulmonary disease (COPD). There is a growing interest in the use of anticholinergic medications in the treatment of moderate to severe asthma. The purpose of this review is to summarize the scientific evidence for the use of anticholinergic therapy in the management of asthma.Recent findingsEarly case reports and small studies evaluated the use of the anticholinergic agent, tiotropium bromide, as maintenance therapy in asthma. Included in this review are several recent clinical trials which provide additional evidence for the use of tiotropium as add-on therapy for asthma. The use of tiotropium was demonstrated to be superior to doubling the dose of an inhaled corticosteroid (ICS) and more effective than placebo based on change in morning peak expiratory flow (PEF). Two large multinational trials provide evidence for the use of tiotropium in a subset of asthmatic patients who have not achieved control using combination therapy with an ICS and a long-acting (2) agonist (LABA).SummaryThe use of the long-acting anticholinergic agent, tiotropium, as maintenance of therapy in asthma, has been shown to be effective in some patients with moderate to severe asthma who are uncontrolled on combination therapy with ICS and LABA. Further studies are needed to better define which phenotypic subset of patients would benefit from the use of tiotropium. C1 [Guyer, Autumn Chandler; Long, Aidan Angelo] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Long, AA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Cox 201, Boston, MA 02114 USA. EM Aalong@partners.org NR 37 TC 8 Z9 8 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 EI 1473-6322 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD AUG PY 2013 VL 13 IS 4 BP 392 EP 398 DI 10.1097/ACI.0b013e328362a775 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 247GL UT WOS:000326604700012 PM 23756872 ER PT J AU Rudders, SA Banerji, A AF Rudders, Susan A. Banerji, Aleena TI An update on self-injectable epinephrine SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE anaphylaxis; auto-injector; epinephrine; food allergy; stinging insect allergy ID AUTOINJECTOR DELIVERY-SYSTEMS; EMERGENCY-DEPARTMENT; AUTO-INJECTORS; UNINTENTIONAL INJECTION; ALLERGIC REACTIONS; FOOD ALLERGIES; PEANUT ALLERGY; NEEDLE LENGTH; ANAPHYLAXIS; CHILDREN AB Purpose of reviewEpinephrine is an important life-saving treatment in patients with anaphylaxis. However, despite the guidelines recommending the use of epinephrine in the management of all patients with anaphylaxis, many patients are either not prescribed epinephrine auto-injectors (EAIs) or remain hesitant to use them.Recent findingsIn this review, we examine our current knowledge base regarding EAIs, including issues related to dosing, medication availability and new modes of administration. Our findings suggest that all patients at risk for anaphylaxis should always carry two epinephrine doses. Once an EAI is prescribed, the patient should receive appropriate education on when and how to use it and it should be administered without delay. Current EAI devices have been redesigned to address limitations and decrease unintentional injury.SummaryEpinephrine remains the cornerstone of anaphylaxis treatment and EAIs are critical because of their ability to rapidly deliver this potentially life-saving medication outside of a medical setting. Continued efforts are needed to establish evidence-based parameters for delivery of this medication and to optimize education of healthcare providers and patients on the use of EAIs. C1 [Rudders, Susan A.] Rhode Isl Hosp, Dept Pediat, Div Allergy & Immunol, Providence, RI 02906 USA. [Banerji, Aleena] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Rudders, SA (reprint author), Rhode Isl Hosp, Hasbro Childrens Hosp, 593 Eddy St, Providence, RI 02906 USA. EM srudders@lifespan.org NR 55 TC 5 Z9 5 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 EI 1473-6322 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD AUG PY 2013 VL 13 IS 4 BP 432 EP 437 DI 10.1097/ACI.0b013e328362b8aa PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 247GL UT WOS:000326604700017 PM 23743514 ER PT J AU Gomez, CA Singh, N AF Gomez, Carlos A. Singh, Nina TI Donor-derived filamentous fungal infections in solid organ transplant recipients SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE aspergillosis; donor-derived infection; mold infections; mucormycosis; solid-organ transplantation; transplant infections ID COMMERCIAL RENAL-TRANSPLANTATION; KIDNEY-TRANSPLANTATION; INVASIVE ASPERGILLOSIS; MUCORMYCOSIS; ALLOGRAFT; RUPTURE; TOURISM; GRAFT; TRANSMISSION; MULTICENTER AB Purpose of reviewFilamentous fungal infections due to rare opportunistic moulds can be transmitted with an allograft. However, epidemiologic and clinical characteristics of donor-derived filamentous fungal infections (DDFFIs) in transplant recipients are poorly understood. Hence, the aim of this article is to describe donor-related risk factors, clinical presentation, graft and recipient outcomes associated with DDFFIs.Recent findingsTo date, 23 cases of donor-derived opportunistic filamentous fungal infections have been reported; a majority (91%) occurred in kidney transplant recipients. Aspergillus spp. was the most common organism (71%). Risk factors for DDFFIs include immunosuppressive state of the donor (transplant recipients serving as organ donors), near-drowning events, and transplant-tourism practices. DDFFIs manifested as vascular complications related to graft vasculature (65%), allograft dysfunction (43%) and unexplained febrile illness (39%) in the recipient. Rates of graft loss and overall mortality were 83 and 17%, respectively.SummaryDonor-transmitted filamentous mycoses have a unique spectrum of illness and clinical settings under which transmission occurs. Prompt recognition, early surgical intervention and specific antifungal therapy are necessary for achieving optimal graft and recipient outcomes. C1 [Gomez, Carlos A.] Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA. [Singh, Nina] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Singh, N (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu NR 49 TC 8 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 EI 1473-6527 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD AUG PY 2013 VL 26 IS 4 BP 309 EP 316 DI 10.1097/QCO.0b013e3283630e4d PG 8 WC Infectious Diseases SC Infectious Diseases GA 248VL UT WOS:000326733200003 PM 23806894 ER PT J AU Kawai, T Sachs, DH AF Kawai, Tatsuo Sachs, David H. TI Tolerance induction: hematopoietic chimerism SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE chimerism; chronic immunosuppression; donor bone marrow transplantation; kidney transplantation; mixed chimerism; tolerance ID RENAL-ALLOGRAFT REJECTION; KIDNEY-TRANSPLANT RECIPIENTS; BONE-MARROW-TRANSPLANTATION; DONOR-SPECIFIC TOLERANCE; MEMORY T-CELLS; MIXED CHIMERISM; NONHUMAN-PRIMATES; STEM-CELL; CYNOMOLGUS MONKEYS; IMMUNOSUPPRESSIVE DRUGS AB Purpose of reviewAlthough numerous experimental models to induce allograft tolerance have been reported, it has been difficult to translate these basic studies to clinical transplantation. However, successful induction of tolerance in HLA-mismatched kidney transplantation has recently been reported. In this review, recent progress in tolerance induction in preclinical (nonhuman primates) and clinical transplantation is summarized.Recent findingsAmong many clinical trials to induce renal allograft tolerance, success has so far been achieved only by combining donor bone marrow with organ transplantation. Induction of renal allograft tolerance by transient or durable mixed chimerism has been reported in HLA-matched or mismatched kidney transplant recipients. More recently, renal allograft tolerance by induction of full donor chimerism has also been reported using a more intensified preparative conditioning regimen.SummaryDurable allograft tolerance has been achieved by induction of hematopoietic chimerism in clinical kidney transplantation, with outstanding long-term results in successful cases. However, these approaches have been associated with higher early complications than are seen following transplantation with conventional immunosuppression. Improvements in the consistency and safety of tolerance induction and extension of successful protocols to other organs will be the next steps in bringing tolerance to a wider range of clinical applications. C1 [Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Surg, Boston, MA 02114 USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, MGH White 521,55 Fruit St, Boston, MA 02114 USA. EM tkawai@partners.org FU NIH [AI102405-01]; Immune Tolerance Network [N01-AI-15416] FX Supported in part by NIH AI102405-01 and the Immune Tolerance Network (N01-AI-15416). NR 84 TC 16 Z9 17 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD AUG PY 2013 VL 18 IS 4 BP 402 EP 407 DI 10.1097/MOT.0b013e328363621d PG 6 WC Transplantation SC Transplantation GA 249AC UT WOS:000326747400003 PM 23838644 ER PT J AU Turka, LA Li, XC Susal, C AF Turka, Laurence A. Li, Xian Chang Suesal, Caner TI Untitled SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Editorial Material C1 [Turka, Laurence A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Turka, Laurence A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Turka, Laurence A.] Univ Penn, Philadelphia, PA 19104 USA. [Turka, Laurence A.; Li, Xian Chang] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Turka, Laurence A.] Amer Soc Transplantat, Mt Laurel, NJ USA. [Turka, Laurence A.] NIAID, Board Sci Counselors, Bethesda, MD USA. [Li, Xian Chang] Methodist Hosp, Houston, TX 77030 USA. [Li, Xian Chang] Methodist Hosp, Transplant Immunol Ctr, Res Inst, Houston, TX 77030 USA. RP Turka, LA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD AUG PY 2013 VL 18 IS 4 DI 10.1097/MOT.0b013e3283646caa PG 2 WC Transplantation SC Transplantation GA 249AC UT WOS:000326747400016 ER PT J AU Faris, C Lindsay, R AF Faris, Callum Lindsay, Robin TI Current thoughts and developments in facial nerve reanimation SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Review DE facial nerve injury; facial paralysis; facial reanimation; free gracilis muscle transfer ID LENGTHENING TEMPORALIS MYOPLASTY; GRACILIS MUSCLE TRANSPLANTATION; QUALITY-OF-LIFE; MOTOR-NERVE; PARALYZED FACE; THERAPEUTIC STRATEGIES; COMPREHENSIVE APPROACH; TENDON TRANSPOSITION; ADULT PATIENTS; MASSETER AB Purpose of reviewTo present the most current literature regarding the management of acute and chronic facial paralysis. This review will focus primarily on smile reanimation in the setting of acute and chronic facial paralysis. The management of the flaccid and the hypertonic face will be discussed. Recent findingsRecent developments include advances in neural repair with fibrin glue and the use of cadaveric nerve grafts as interposition grafts. Advances in nerve substitutes have been shown to limit donor-site morbidity and provide similar outcomes to autografts. Techniques for muscle transfer continue to evolve to improve smile outcomes. SummaryThe goal of facial reanimation surgery is to restore meaningful facial movement. The goal should be to have quality-driven clinical practice guidelines to better facilitate patient care. This process must be initiated by facial reanimation surgeons deciding to use consistent outcome measures to report their results. Currently, it is impossible to make a direct comparison between different surgical techniques because of inconsistent methods of evaluation. Despite the lack of consistent quantitative evaluation, there have been many exciting advances in the field. C1 [Faris, Callum] Univ Nottingham Hosp, Queens Med Ctr, Dept Otolaryngol Head & Neck Surg, Nottingham NG7 2UH, England. [Lindsay, Robin] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. RP Lindsay, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM robin_lindsay@meei.harvard.edu NR 47 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9508 EI 1531-6998 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD AUG PY 2013 VL 21 IS 4 BP 346 EP 352 DI 10.1097/MOO.0b013e328362a56e PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 248XV UT WOS:000326740200008 PM 23756337 ER PT J AU Bhama, P Bhrany, AD AF Bhama, Prabhat Bhrany, Amit D. TI Ocular protection in facial paralysis SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Review DE ectropion; facial paralysis; lagophthalmos; ocular protection ID GOLD WEIGHT; BOTULINUM TOXIN; CORNEAL PROTECTION; LAGOPHTHALMOS; MANAGEMENT; SURGERY; GRAFT; ECTROPION; PTOSIS; EYE AB Purpose of reviewFacial nerve paralysis has a profound impact on patients' quality of life, of which one of the most important sequelae is a risk of corneal surface disease. Herein, we discuss methods to protect the eye following insult to the facial nerve. Recent findingsProtection of the ocular surface in patients with facial nerve injury is of paramount importance to prevent corneal injury and potential blindness. Many interventions on the eye are temporary and therefore easily reversible. A systematic approach to managing the eye is required in these patients. SummaryThis article provides a review of current methods used for ocular protection in patients with facial nerve paralysis. C1 [Bhama, Prabhat] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Facial Plast & Reconstruct Surg,Dept Otol & L, Boston, MA USA. [Bhrany, Amit D.] Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. RP Bhrany, AD (reprint author), Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Box 356515, Seattle, WA 98195 USA. EM abhrany@uw.edu NR 25 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9508 EI 1531-6998 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD AUG PY 2013 VL 21 IS 4 BP 353 EP 357 DI 10.1097/MOO.0b013e32836239cf PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 248XV UT WOS:000326740200009 PM 23689596 ER PT J AU Winter, HS Di Lorenzo, C Benninga, MA Gilger, MA Kearns, GL Hyman, PE Vandeplassche, L Ausma, J Hoppenbrouwers, M AF Winter, Harland S. Di Lorenzo, Carlo Benninga, Marc A. Gilger, Mark A. Kearns, Gregory L. Hyman, Paul E. Vandeplassche, Lieve Ausma, Jannie Hoppenbrouwers, Mieke TI Oral Prucalopride in Children With Functional Constipation SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE efficacy; functional constipation; pharmacokinetics; prucalopride; tolerability ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CHILDHOOD CONSTIPATION; INTRACTABLE CONSTIPATION; HEALTHY-VOLUNTEERS; COLONIC MOTILITY; CISAPRIDE; TRANSIT; AGONIST AB Background and Objectives:Prucalopride is a selective, high-affinity 5-HT4 receptor agonist with gastrointestinal prokinetic activities. The aim of this study was to evaluate the pharmacokinetics, efficacy, safety, and tolerability of prucalopride oral solution in children, ages 4 years or older to 12 years or younger, with functional constipation.Methods:A single oral dose of 0.03 mg/kg prucalopride was administered to 38 children to characterize prucalopride pharmacokinetics (NCT01674166). Thereafter, 37 children entered an open-label extension period in which 0.01 to 0.03 mg/kg of prucalopride was administered once per day for 8 weeks to investigate efficacy, safety, and tolerability (NCT01670669).Results:Mean (standard deviation [SD]) C-max, t(max), and AUC (area under the plasma concentration-time curve from time 0 to infinity) were 3.8 (0.6) ng/mL, 1.8 (0.9) hour, and 65.3 (10.6) ng h(-1) mL(-1), respectively, with limited (16%) variability in C-max and AUC. Mean (SD) t(1/2) was 19.0 (3.1) hours. On average, mean (SD) renal clearance (0.25 [0.08] L h(-1) kg(-1)) accounted for 54% of the apparent total plasma clearance (0.46 [0.07] L h(-1) kg(-1)). The apparent volume of distribution was 12.6 (2.6) L/kg. Prucalopride treatment resulted in a mean bowel movement frequency of 6.8/week, normal stool consistency, and reduced frequency of fecal incontinence. During the 8-week extension, 70% of study participants had at least 1 adverse event (all but 1 of mild/moderate intensity, 19% considered related to prucalopride). No children discontinued prucalopride because of adverse events.Conclusions:The pharmacokinetic profile of a single dose of prucalopride oral solution (0.03 mg kg(-1) day(-1)) generally resembled the profile in adults (2-mg tablet) but reflected lower systemic exposure in children. Prucalopride treatment for 8 weeks demonstrated an apparent favorable efficacy and tolerability profile in children with functional constipation. C1 [Winter, Harland S.] MassGen Hosp Children, Boston, MA 02114 USA. [Di Lorenzo, Carlo] Nationwide Childrens Hosp, Columbus, OH USA. [Benninga, Marc A.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Gilger, Mark A.] Texas Childrens Hosp, Houston, TX 77030 USA. [Kearns, Gregory L.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Hyman, Paul E.] Childrens Hosp, New Orleans, LA USA. [Vandeplassche, Lieve; Ausma, Jannie; Hoppenbrouwers, Mieke] Shire Movetis NV, Turnhout, Belgium. RP Winter, HS (reprint author), MassGen Hosp Children, Pediat GI Unit, CRPZ 5-560,175 Cambridge St, Boston, MA 02114 USA. EM hwinter@partners.org FU UCB, Nutricia; Pediatric IBD Foundation; Autism Research Institute; Warner-Chilcott.; Redhill Biopharma; QOL Medical; Otsuka Pharmaceutical Inc; National Institutes of Health [NO1 A1 25465]; Bristol-Myers Squibb; National Institutes of Health; Janssen Research Foundation, Beerse, Belgium; Shire-Movetis NV, Turnhout, Belgium FX H.S.W. has current research grants from Janssen, UCB, Nutricia, The Pediatric IBD Foundation, Autism Research Institute, and Warner-Chilcott. He has current consulting agreements with Prometheus Laboratories, Salix, Janssen Pharmaceuticals, and Shire-Movetis NV. C. D. has consulting agreements with Janssen Pharmaceuticals, Abbott Laboratories, Ironwood Pharmaceuticals, and QOL Medical. M. A. B. has consulting agreements with Shire-Movetis NV and Danone. M. A. G. has current research grants from Redhill Biopharma, QOL Medical, Otsuka Pharmaceutical Inc, and the National Institutes of Health (NO1 A1 25465). G. L. K. has active consulting agreements with Upsher-Smith Laboratories, Inc, Solginex, Inc, and Bristol-Myers Squibb. He has current research grants from Bristol-Myers Squibb and the National Institutes of Health. L. V., J.A., and M. H. are employees of Shire-Movetis NV and own stock in Shire. P. E. H. reports no conflicts of interest.; The clinical research was funded by the Janssen Research Foundation, Beerse, Belgium, and Shire-Movetis NV, Turnhout, Belgium. Although Janssen Research Foundation and Shire-Movetis NV were involved in the design, collection, analysis, interpretation, and fact checking of the information, the content of this manuscript, the ultimate interpretation, and the decision to submit it for publication was made by the authors independently. NR 29 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD AUG PY 2013 VL 57 IS 2 BP 197 EP 203 DI 10.1097/MPG.0b013e318292f9ea PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 249AM UT WOS:000326748700017 PM 23535761 ER PT J AU Golwala, HB Thadani, U Liang, L Stavrakis, S Butler, J Yancy, CW Bhatt, DL Hernandez, AF Fonarow, GC AF Golwala, Harsh B. Thadani, Udho Liang, Li Stavrakis, Stavros Butler, Javed Yancy, Clyde W. Bhatt, Deepak L. Hernandez, Adrian F. Fonarow, Gregg C. TI Use of Hydralazine-Isosorbide Dinitrate Combination in African American and Other Race/Ethnic Group Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE guideline adherence; heart failure; quality; race/ethnicity; registry ID RANDOMIZED-TRIAL; MORTALITY; SURVIVAL; MORBIDITY; ENALAPRIL; GENDER; ASSOCIATION; CARVEDILOL; GUIDELINES; HF AB Background-Hydralazine-isosorbide dinitrate (H-ISDN) therapy is recommended for African American patients with moderate to severe heart failure with reduced ejection fraction (<40%) (HFrEF), but use, temporal trends, and clinical characteristics associated with H-ISDN therapy in clinical practice are unknown. Methods and Results-An observational analysis of 54 622 patients admitted with HFrEF and discharged home from 207 hospitals participating in the Get With The Guidelines-Heart Failure registry from April 2008 to March 2012 was conducted to assess prescription, trends, and predictors of use of H-ISDN among eligible patients. Among 11 185 African American patients eligible for H-ISDN therapy, only 2500 (22.4%) received H-ISDN therapy at discharge. In the overall eligible population, 5115 of 43 498 (12.6%) received H-ISDN at discharge. Treatment rates increased over the study period from 16% to 24% among African Americans and from 10% to 13% among the entire HFrEF population. In a multivariable model, factors associated with H-ISDN use among the entire cohort included younger age; male sex; African American/Hispanic ethnicity; and history of diabetes, hypertension, anemia, renal insufficiency, higher systolic blood pressure, and lower heart rate. In African American patients, these factors were similar; in addition, being uninsured was associated with lower use. Conclusions-Overall, few potentially eligible patients with HFrEF are treated with H-ISDN, and among African-Americans fewer than one-fourth of eligible patients received guideline-recommended H-ISDN therapy. Improved ways to facilitate use of H-ISDN therapy in African American patients with HFrEF are needed. C1 [Golwala, Harsh B.; Thadani, Udho; Stavrakis, Stavros] Univ Oklahoma, Hlth Sci Ctr, VA Med Ctr, Oklahoma City, OK USA. [Liang, Li; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Yancy, Clyde W.] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. RP Fonarow, GC (reprint author), Ahmanson UCLA Cardiomyopathy Ctr, Ronald Reagan UCLA Med Ctr, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu FU Medtronic; GlaxoSmithKline; Ortho-McNeil; American Heart Association Pharmaceutical Roundtable FX The Get With The Guidelines-Heart Failure (GWTG-HF) program is provided by the American Heart Association. GWTG-HF has been funded in the past through support from Medtronic, GlaxoSmithKline, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable. NR 24 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2013 VL 2 IS 4 AR e000214 DI 10.1161/JAHA.113.000214 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243TP UT WOS:000326340900013 PM 23966379 ER PT J AU Larsen, M Bartnes, K Tsai, TT Eagle, KA Evangelista, A Nienaber, CA Suzuki, T Fattori, R Froehlich, JB Hutchison, S Sundt, TM Januzzi, JL Isselbacher, EM Montgomery, DG Myrmel, T AF Larsen, Magnus Bartnes, Kristian Tsai, Thomas T. Eagle, Kim A. Evangelista, Arturo Nienaber, Christoph A. Suzuki, Toru Fattori, Rossella Froehlich, James B. Hutchison, Stuart Sundt, Thoralf M. Januzzi, James L. Isselbacher, Eric M. Montgomery, Daniel G. Myrmel, Truls TI Extent of Preoperative False Lumen Thrombosis Does Not Influence Long-Term Survival in Patients With Acute Type A Aortic Dissection SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE aortic dissection; prognosis; surgery; thrombosis ID INTERNATIONAL-REGISTRY; RISK-FACTORS; OPERATIVE STRATEGY; ARCH REPLACEMENT; REPAIR; INSIGHTS; OUTCOMES; PATENCY; FATE; IRAD AB Background-Partial thrombosis of the false lumen has been related to aortic growth, reoperations, and death in the chronic phase of type B and repaired type A aortic dissections. The impact of preoperative false lumen thrombosis has not been studied previously. We used data from a contemporary, multinational database on aortic dissections to evaluate whether different degrees of preoperative false lumen thrombosis influenced long-term prognosis. Methods and Results-We examined the records of 522 patients with surgically treated acute type A aortic dissections who survived to discharge between 1996 and 2011. At the preoperative imaging, 414 (79.3%) patients had patent false lumens, 84 (16.1%) had partial thrombosis of the false lumen, and 24 (4.6%) had complete thrombosis of the false lumen. The annual median (interquartile range) aortic growth rates were 0.5 (-0.3 to 2.0) mm in the aortic arch, 2.0 (0.2 to 4.0) mm in the descending thoracic aorta, and similar regardless of the degree of false lumen thrombosis. The overall 5-year survival rate was 84.7%, and it was not influenced by false lumen thrombosis (P=0.86 by the log-rank test). Independent predictors of long-term mortality were age >70 years (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.20 to 4.56, P=0.012) and postoperative cerebrovascular accident, coma, and/or renal failure (HR, 2.62; 95% CI, 1.40 to 4.92, P=0.003). Conclusions-Patients with acute type A aortic dissection who survive to discharge have a favorable prognosis. Preoperative false lumen thrombosis does not influence long-term mortality, reintervention rates, or aortic growth. C1 [Larsen, Magnus; Bartnes, Kristian; Myrmel, Truls] Univ Hosp North Norway, Dept Cardiothorac & Vasc Surg, N-9038 Tromso, Norway. [Larsen, Magnus; Bartnes, Kristian; Myrmel, Truls] Univ Tromso, Fac Med, Tromso, Norway. [Tsai, Thomas T.] Univ Colorado Hosp, Aurora, CO USA. [Eagle, Kim A.; Froehlich, James B.; Montgomery, Daniel G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Evangelista, Arturo] Univ Vall DHebron, Gen Hosp, Barcelona, Spain. [Nienaber, Christoph A.] Univ Hosp Eppendorf Rostock, Rostock, Germany. [Suzuki, Toru] Univ Tokyo, Tokyo, Japan. [Fattori, Rossella] Univ Hosp S Orsola, Bologna, Italy. [Hutchison, Stuart] Univ Calgary, Med Ctr, Calgary, AB, Canada. [Sundt, Thoralf M.; Januzzi, James L.; Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Larsen, M (reprint author), Univ Hosp North Norway, Dept Cardiothorac & Vasc Surg, N-9038 Tromso, Norway. EM magnus.larsen@unn.no FU W.L. Gore & Associates, Inc; Varbedian Fund for Aortic Research; Hewlett Foundation; Mardigian Foundation; University of Michigan Group Practise; Terumo; Norwegian Health Association, Norwegian Council on Cardiovascular Diseases, Oslo, Norway FX The International Registry of Acute Aortic Dissections receives funding from the following sources: W.L. Gore & Associates, Inc, the Varbedian Fund for Aortic Research, Hewlett Foundation, the Mardigian Foundation, the University of Michigan Group Practise and Terumo. Dr Larsen is supported by a research grant from the Norwegian Health Association, Norwegian Council on Cardiovascular Diseases, Oslo, Norway. NR 33 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2013 VL 2 IS 4 AR e000112 DI 10.1161/JAHA.113.000112 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243TP UT WOS:000326340900020 PM 23817468 ER PT J AU Rodriguez, F Hong, C Chang, YC Oertel, LB Singer, DE Green, AR Lopez, LL AF Rodriguez, Fatima Hong, Clemens Chang, Yuchiao Oertel, Lynn B. Singer, Daniel E. Green, Alexander R. Lopez, Lenny L. TI Limited English Proficient Patients and Time Spent in Therapeutic Range in a Warfarin Anticoagulation Clinic SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE adverse drug events; limited English proficiency; outcomes research; quality of care; warfarin ID NONVALVULAR ATRIAL-FIBRILLATION; QUALITY-OF-CARE; HEALTH-CARE; LANGUAGE BARRIERS; UNITED-STATES; INTERPRETER SERVICES; ORAL ANTICOAGULANT; STROKE PREVENTION; ADVERSE EVENTS; US HISPANICS AB Background-While anticoagulation clinics have been shown to deliver tailored, high-quality care to patients receiving warfarin therapy, communication barriers with limited English proficient (LEP) patients may lead to disparities in anticoagulation outcomes. Methods and Results-We analyzed data on 3770 patients receiving care from the Massachusetts General Hospital Anticoagulation Management Service (AMS) from 2009 to 2010. This included data on international normalized ratio (INR) tests and patient characteristics, including language and whether AMS used a surrogate for primary communication. We calculated percent time in therapeutic range (TTR for INR between 2.0 and 3.0) and time in danger range (TDR for INR <1.8 or >3.5) using the standard Rosendaal interpolation method. There were 241 LEP patients; LEP patients, compared with non-LEP patients, had a higher number of comorbidities (3.2 versus 2.9 comorbidities, P=0.004), were more frequently uninsured (17.0% versus 4.3%, P<0.001), and less educated (47.7% versus 6.0% <= high school education, P<0.001). LEP patients compared with non-LEP patients spent less TTR (71.6% versus 74.0%, P=0.007) and more TDR (12.9% versus 11.3%, P=0.018). In adjusted analyses, LEP patients had lower TTR as compared with non-LEP patients (OR 1.5, 95% CI [ 1.1, 2.2]). LEP patients who used a communication surrogate spent less TTR and more TDR. Conclusion-Even within a large anticoagulation clinic with a high average TTR, a small but significant decrease in TTR was observed for LEP patients compared with English speakers. Future studies are warranted to explore how the use of professional interpreters impact TTR for LEP patients. C1 [Lopez, Lenny L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Rodriguez, Fatima; Lopez, Lenny L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rodriguez, Fatima; Hong, Clemens; Chang, Yuchiao; Singer, Daniel E.; Green, Alexander R.; Lopez, Lenny L.] Harvard Univ, Sch Med, Boston, MA USA. [Hong, Clemens; Chang, Yuchiao; Singer, Daniel E.; Lopez, Lenny L.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Oertel, Lynn B.] Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. [Green, Alexander R.; Lopez, Lenny L.] Massachusetts Gen Hosp, Disparities Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny L.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Rodriguez, F (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM farodriguez@partners.org FU Daiichi Sankyo; Johnson and Johnson FX Daniel E. Singer has received research grants from Daiichi Sankyo and Johnson and Johnson and served as a consultant to Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson and Johnson, and Pfizer, all manufacturers of novel anticoagulants. The other authors have no conflicts to declare. NR 43 TC 5 Z9 5 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2013 VL 2 IS 4 AR e000170 DI 10.1161/JAHA.113.000170 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243TP UT WOS:000326340900032 PM 23832325 ER PT J AU Shah, RV Abbasi, SA Neilan, TG Hulten, E Coelho, O Hoppin, A Levitsky, L de Ferranti, S Rhodes, ET Traum, A Goodman, E Feng, H Heydari, B Harris, WS Hoefner, DM McConnell, JP Seethamraju, R Rickers, C Kwong, RY Jerosch-Herold, M AF Shah, Ravi V. Abbasi, Siddique A. Neilan, Tomas G. Hulten, Edward Coelho-Filho, Otavio Hoppin, Alison Levitsky, Lynne de Ferranti, Sarah Rhodes, Erinn T. Traum, Avram Goodman, Elizabeth Feng, Henry Heydari, Bobak Harris, William S. Hoefner, Daniel M. McConnell, Joseph P. Seethamraju, Ravi Rickers, Carsten Kwong, Raymond Y. Jerosch-Herold, Michael TI Myocardial Tissue Remodeling in Adolescent Obesity SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE CT or MRI; obesity; type 2 diabetes ID CARDIOVASCULAR MAGNETIC-RESONANCE; LEFT-VENTRICULAR MASS; TRANSCYTOLEMMAL WATER-EXCHANGE; EXTRACELLULAR-MATRIX EXPANSION; INSULIN-RESISTANCE; HEART-DISEASE; DIABETIC CARDIOMYOPATHY; VOLUME FRACTION; CHILDREN; ASSOCIATION AB Background-Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue-level markers within the myocardium that precede organ-level alterations have not been described. Methods and Results-We studied 21 obese adolescents (mean age, 17.7 +/- 2.6 years; mean body mass index [BMI], 41.9 +/- 9.5 kg/m(2), including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1 +/- 4.5 years; BMI, 20.1 +/- 3.5 kg/m(2)) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size-adjusted limits), interstitial matrix expansion by CMR extracellular volume fraction (ECV) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire population (r=0.58, P<0.001) and with high-sensitivity C-reactive protein (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c (r=0.76, P<0.0001) in the obese stratum. Conclusions-Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function. C1 [Shah, Ravi V.; Abbasi, Siddique A.; Neilan, Tomas G.; Hulten, Edward; Feng, Henry; Heydari, Bobak; Kwong, Raymond Y.; Jerosch-Herold, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div,Noninvas Cardiovasc Imagi, Boston, MA 02115 USA. [Shah, Ravi V.; Abbasi, Siddique A.; Neilan, Tomas G.; Hulten, Edward; Feng, Henry; Heydari, Bobak; Kwong, Raymond Y.; Jerosch-Herold, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shah, Ravi V.; Neilan, Tomas G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. [Coelho-Filho, Otavio] State Univ Campinas UNICAMP, Div Cardiol, Campinas, SP, Brazil. [Hoppin, Alison] MassGen Hosp Children, Div Gastroenterol, Boston, MA USA. [Levitsky, Lynne] MassGen Hosp Children, Div Endocrinol, Boston, MA USA. [Traum, Avram] MassGen Hosp Children, Div Nephrol, Boston, MA USA. [Goodman, Elizabeth] MassGen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [de Ferranti, Sarah] Boston Childrens Hosp, Boston, MA USA. [Rhodes, Erinn T.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Harris, William S.; Hoefner, Daniel M.; McConnell, Joseph P.] Hlth Diagnost Lab, Richmond, VA USA. [Seethamraju, Ravi] Siemens Healthcare, Erlangen, Germany. RP Jerosch-Herold, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM mjerosch-herold@partners.org FU Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard University; American Heart Association [11POST000002, 12FTF12060588]; Heart Failure NIH Clinical Research Network [U01-HL084877]; NIH [R01-HL091157] FX This work was conducted with support from Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. Dr Shah is supported by an American Heart Association Post-Doctoral Fellowship Award (11POST000002) and a training grant from the Heart Failure NIH Clinical Research Network (U01-HL084877). Dr Neilan is supported by a grant from the American Heart Association Fellow-to-Faculty Award (12FTF12060588). Dr Jerosch-Herold is supported by NIH grant R01-HL091157. Studies were, in part, donated by Siemens Healthcare. NR 48 TC 18 Z9 18 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2013 VL 2 IS 4 AR e000279 DI 10.1161/JAHA.113.000279 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243TP UT WOS:000326340900038 PM 23963758 ER PT J AU Burstein, H AF Burstein, Harold TI Expert opinion vs guideline based care: The St. Gallen Case study SO BREAST LA English DT Editorial Material C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, H (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD AUG 1 PY 2013 VL 22 SU 2 BP S1 EP S2 DI 10.1016/j.breast.2013.07.036 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 243JG UT WOS:000326312100001 PM 23906475 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Patients with triple negative breast cancer: Is there an optimal adjuvant treatment? SO BREAST LA English DT Editorial Material ID RANDOMIZED-TRIALS; DOCETAXEL; CYCLOPHOSPHAMIDE; PACLITAXEL; SURVIVAL; SUBTYPES; WOMEN; HER2 C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 13 TC 4 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD AUG 1 PY 2013 VL 22 SU 2 BP S147 EP S148 DI 10.1016/j.breast.2013.07.027 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 243JG UT WOS:000326312100029 PM 24074776 ER PT J AU Freedman, RA Partridge, AH AF Freedman, Rachel A. Partridge, Ann H. TI Management of breast cancer in very young women SO BREAST LA English DT Article DE Breast cancer; Young women; Age; Premenopausal ID CONSERVING THERAPY; RANDOMIZED-TRIALS; CONSERVATION THERAPY; ADJUVANT TAMOXIFEN; LARGE COHORT; SURVIVAL; AGE; RECURRENCE; DIAGNOSIS; STAGE AB Breast cancer is the leading cause of cancer-related deaths in women age 40 and younger in developed countries, and although generally improving, survival rates for young women with breast cancer remain lower than for older women. Young women are more likely to develop more aggressive subtypes of breast cancer and previous research has suggested that young age is an independent risk factor for disease recurrence and death, and there may be unique biologic features of breast cancer that occurs in young women. Certainly, there are host differences biologically as well as psychosocially that affect the management of breast cancer and survivorship concerns for young women compared to older women. Multi-agent chemotherapy and biologic therapy targeting the tumor similar to the treatment in older women is standard, with careful attention to unique survivorship concerns including genetics, infertility, and psychosocial issues. Select young women will do well with hormone therapy only, although at present, the optimal hormonal therapy for very young women remains unclear. Recent data demonstrating that 10 years of tamoxifen improves outcomes compared to 5 may be particularly beneficial for young women with hormone receptor-positive tumors given the risk benefit profile. Future and ongoing studies focused on breast cancer in young women, addressing both biology as well as psychosocial issues, including supportive care interventions should improve outcomes for young women with breast cancer. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Freedman, Rachel A.; Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Partridge, AH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org; ahpartridge@partners.org NR 44 TC 12 Z9 13 U1 1 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD AUG 1 PY 2013 VL 22 SU 2 BP S176 EP S179 DI 10.1016/j.breast.2013.07.034 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 243JG UT WOS:000326312100036 PM 24074783 ER PT J AU Mouw, KW Harris, JR AF Mouw, Kent W. Harris, Jay R. TI Hypofractionation in the era of modulated radiotherapy (RT) SO BREAST LA English DT Article DE Breast-conserving therapy; Hypofractionation ID EARLY BREAST-CANCER; 20-YEAR FOLLOW-UP; RANDOMIZED-TRIAL; RADIATION-THERAPY; CONSERVING SURGERY; UK STANDARDIZATION; LOCAL RECURRENCE; MASTECTOMY; BOOST; COMPLICATIONS AB The use of radiation therapy (RI) as a component of breast-conserving therapy (BCT) has been shown to reduce the risk of local-regional recurrence and improve overall survival. As has been the common practice in the United States and Continental Europe, the majority of studies that demonstrated these benefits utilized daily radiation doses ranging from 1.8 to 2.0 Gray (Gy) per day given for approximately 5 weeks. However, due to geographic limitations, patient preferences, and financial considerations, there have been continued attempts to evaluate the efficacy and safety of abbreviated or hypofractionated courses of whole-breast radiation. Two key factors in these attempts have been: 1) advances in radiobiology allowing for a more precise estimation of equivalent dosing, and 2) advances in the delivery of RT ('modulation') that have resulted in substantially improved dose homogeneity in the target volume. Hypofractionated schedules have been compared to conventional radiation courses in several randomized controlled trials, as well as many prospective and retrospective experiences. These studies, now with about 10 years of follow-up, have demonstrated equivalent rates of local-regional recurrence, disease-free survival, and overall survival. The rates of toxicity have generally not been increased with hypofractionated regimens; however, certain toxicities may take decades to manifest. The generalizability of these results is unclear, as the majority of patients in the trials were elderly with early-stage hormone-receptor positive disease. Nevertheless, there is now sufficient evidence to recommend hypofractionated whole breast RI for a substantial percentage of patients. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Mouw, Kent W.] Harvard Radiat Oncol Program, Boston, MA USA. [Harris, Jay R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Harris, Jay R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Harris, JR (reprint author), Dana Farber Canc Inst, Dana Bldg Room 1622,450 Brookline Ave, Boston, MA 02115 USA. EM jharris@lroc.harvard.edu NR 34 TC 2 Z9 4 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD AUG 1 PY 2013 VL 22 SU 2 BP S129 EP S136 DI 10.1016/j.breast.2013.07.024 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 243JG UT WOS:000326312100026 PM 24074773 ER PT J AU Strasser-Weippl, K Badovinac-Crnjevic, T Fan, L Goss, PE AF Strasser-Weippl, Kathrin Badovinac-Crnjevic, Tanja Fan, Lei Goss, Paul E. TI Extended adjuvant endocrine therapy in hormone-receptor positive breast cancer SO BREAST LA English DT Article DE Extended treatment; Breast cancer; Endocrine; Adjuvant ID TO-TREAT ANALYSIS; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; UPDATED FINDINGS; NCICCTG MA.17; LETROZOLE; EXEMESTANE; METAANALYSIS; OUTCOMES AB A high ongoing recurrence rate in patients with endocrine responsive breast cancer provides the rationale for offering endocrine treatment for more than five years. The MA.17 study, comparing the aromatase inhibitor (AI) letrozole for five years after an initial five years of tamoxifen to no further treatment, provided the proof-of-principle for extended endocrine treatment. These results have meanwhile been confirmed by several other studies and an EBCTCG meta-analysis. More recently, data from the ATLAS trial, comparing 10 to five years of tamoxifen, have been published, similarly showing a benefit for longer endocrine treatment with tamoxifen. In postmenopausal women -including those who had been premenopausal at initial diagnosis - a cross-trial comparison of ATLAS and the AI studies indicates superiority of switching to letrozole versus ongoing tamoxifen, similar to superiority of the AIs over tamoxifen in the metastatic and early breast cancer settings. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol Hematol & Palliat Care, A-1160 Vienna, Austria. [Badovinac-Crnjevic, Tanja; Fan, Lei; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Badovinac-Crnjevic, Tanja; Fan, Lei; Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House LRH-302, Boston, MA 02114 USA. EM Kathrin.strasserweippl@gmail.com; pgoss@partners.org FU GSK; Novartis; Pfizer FX Paul Goss has received speaker's fees from GSK, Novartis and Pfizer. NR 31 TC 12 Z9 12 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD AUG 1 PY 2013 VL 22 SU 2 BP S171 EP S175 DI 10.1016/j.breast.2013.07.033 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 243JG UT WOS:000326312100035 PM 24074782 ER PT J AU Stewart, AJ Hepel, JT O'Farrell, DA Devlin, PM Price, LL Dale, RG Wazer, DE AF Stewart, Alexandra J. Hepel, Jaroslaw T. O'Farrell, Desmond A. Devlin, Phillip M. Price, Lori Lyn Dale, Roger G. Wazer, David E. TI Equivalent uniform dose for accelerated partial breast irradiation using the MammoSite applicator SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Equivalent uniform dose; MammoSite catheter; Radiobiology; Toxicity analysis ID HOSPITAL EXPERIENCE; BRACHYTHERAPY; TOXICITY; OPTIMIZATION; CANCER AB Introduction: This study aims to quantify the radiobiology of the MammoSite applicator and examine whether there is a relationship between equivalent uniform dose (EUD) and radiotherapy-associated toxicity. Methods and materials: A previously-published version of the linear quadratic (LQ) model, designed to address the impact of dose-gradients in brachytherapy applications, was used to determine the biological effective dose (BED), equivalent dose in 2 Gray per fraction (EQD(2)) and EUD for the most common fractionation scheme for the MammoSite catheter (34 Gy in 10 fractions prescribed to 1 cm from the balloon surface), using a range of balloon sizes in a series of patients treated with single or multiple dwell positions. Toxicity from the MammoSite catheter was assessed and statistical associations with the calculated EUDs were investigated. Results: The acute- and late-toxicity EUDs respectively range from 34.8-39.4 Gy and 33.4-37.6 Gy, with EUD decreasing as balloon diameter increases and/or the number of dwell positions increases. There was a positive association between EUD and hyperpigmentation and telangiectasia. Conclusions: For APBI using the Mammosite applicator, EUD is higher than the marginal prescription dose and, for the dose-fractionation patterns considered here, was associated with acute and late skin toxicity. EUD is a potentially useful parameter to characterize non-uniform dose distributions related to brachytherapy treatments. Further evaluation in future studies is warranted. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Stewart, Alexandra J.] Royal Surrey Cty Hosp, St Lukes Canc Ctr, Guildford GU2 7XX, Surrey, England. [Hepel, Jaroslaw T.; Wazer, David E.] Tufts Univ, Tufts Med Ctr, Dept Radiat Oncol, Boston, MA 02111 USA. [Hepel, Jaroslaw T.; Wazer, David E.] Brown Univ, Rhode Isl Hosp, Dept Radiat Oncol, Providence, RI 02903 USA. [O'Farrell, Desmond A.; Devlin, Phillip M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. [Price, Lori Lyn] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Biostat Res Ctr, Boston, MA USA. [Dale, Roger G.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Surg & Canc, London, England. RP Stewart, AJ (reprint author), Royal Surrey Cty Hosp, St Lukes Canc Ctr, Egerton Rd, Guildford GU2 7XX, Surrey, England. EM Alexandra.stewart@nhs.net NR 20 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD AUG PY 2013 VL 108 IS 2 BP 232 EP 235 DI 10.1016/j.radonc.2013.06.030 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 241AR UT WOS:000326139300009 PM 23891101 ER PT J AU Rogus-Pulia, N Robbins, J AF Rogus-Pulia, Nicole Robbins, JoAnne TI Approaches to the Rehabilitation of Dysphagia in Acute Poststroke Patients SO SEMINARS IN SPEECH AND LANGUAGE LA English DT Article DE Dysphagia; stroke; acute; rehabilitation; evidence ID NEUROMUSCULAR ELECTRICAL-STIMULATION; ACUTE STROKE PATIENTS; RANDOMIZED CONTROLLED-TRIAL; ACUTE ISCHEMIC-STROKE; OROPHARYNGEAL DYSPHAGIA; SWALLOWING DISORDERS; PHARYNGEAL DYSPHAGIA; ASPIRATION PNEUMONIA; NEUROGENIC DYSPHAGIA; EMERGENCY-DEPARTMENT AB Dysphagia occurs frequently following stroke and may result in serious health consequences including pneumonia, malnutrition, dehydration, and mortality. Prevention of these negative health outcomes requires early identification and treatment of dysphagia. The speech-language pathologist, as part of a multidisciplinary team, holds the primary responsibility for selection of an effective dysphagia rehabilitation program for these patients. Because much research has focused on patients with chronic dysphagia, this review will focus on treatment of patients within the acute phase of recovery poststroke. Although some acute patients may experience transient dysphagia that resolves spontaneously, many will go on to develop chronic dysphagia that may be prevented with provision of early and intensive treatment. An overview of dysphagia following stroke will be provided with information regarding incidence, complications, evaluation, and causes of dysphagia. A thorough discussion of evidence supporting varying approaches to dysphagia rehabilitation will follow with inclusion of several current, novel, and experimental techniques. The importance of the multidisciplinary team and regular reevaluation will be emphasized as well. C1 [Rogus-Pulia, Nicole; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Rogus-Pulia, Nicole; Robbins, JoAnne] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Gastroenterol & Hepatol, Madison, WI USA. RP Rogus-Pulia, N (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Madison GRECC 11G,Room D521, Madison, WI 53705 USA. EM nicolepulia@gmail.com NR 126 TC 5 Z9 6 U1 1 U2 20 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-0478 EI 1098-9056 J9 SEMIN SPEECH LANG JI Semin. Speech Lang. PD AUG PY 2013 VL 34 IS 3 BP 154 EP 169 DI 10.1055/s-0033-1358368 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 242IF UT WOS:000326231800004 PM 24166190 ER PT J AU Kobayashi, K Hosseini, A Sakamoto, M Qi, W Rubash, HE Li, GA AF Kobayashi, Koichi Hosseini, Ali Sakamoto, Makoto Qi, Wei Rubash, Harry E. Li, Guoan TI In Vivo Kinematics of the Extensor Mechanism of the Knee During Deep Flexion SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE patellofemoral contact; weight-bearing activity; patellar tendon force; quadriceps force; knee biomechanics ID PATELLOFEMORAL CONTACT PRESSURES; ANTERIOR CRUCIATE LIGAMENT; 3-DIMENSIONAL TRACKING; TIBIOFEMORAL JOINT; PATELLAR TRACKING; ARTHROPLASTY; STRESS; BIOMECHANICS; FORCES; TENDON AB While various factors have been assumed to affect knee joint biomechanics, few data have been reported on the function of the extensor mechanism in deep flexion of the knee. This study analyzed the patellofemoral joint contact kinematics and the ratio of the quadriceps and patellar tendon forces in living subjects when they performed a single leg lunge up to 150 deg of flexion. The data revealed that in the proximal-distal direction, the patellofemoral articular contact points were in the central one-third of the patellar cartilage. Beyond 90 deg of flexion, the contact points moved towards the medial-lateral edges of the patellar surface. At low flexion angles, the patellar tendon and quadriceps force ratio was approximately 1.0 but reduced to about 0.7 after 60 deg of knee flexion, implying that the patella tendon carries lower loads than the quadriceps. These data may be valuable for improvement of contemporary surgical treatments of diseased knees that are aimed to achieve deep knee flexion. C1 [Kobayashi, Koichi; Hosseini, Ali; Qi, Wei; Rubash, Harry E.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg,Bioengn Lab, Boston, MA 02114 USA. [Kobayashi, Koichi; Sakamoto, Makoto] Niigata Univ, Sch Med, Dept Hlth Sci, Niigata, Japan. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg,Bioengn Lab, Boston, MA 02114 USA. EM gli1@partners.org FU National Institutes of Health [R01AR055612]; Japan Society for the Promotion of Science [C22560074] FX This work was supported by a National Institutes of Health Grant R01AR055612 and a Grant-in-Aid for Scientific Research C22560074 by the Japan Society for the Promotion of Science. NR 37 TC 3 Z9 3 U1 0 U2 9 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 EI 1528-8951 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD AUG PY 2013 VL 135 IS 8 AR 081002 DI 10.1115/1.4024284 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 240HE UT WOS:000326085100003 PM 23719832 ER PT J AU Mort, EA Demehin, AA Marple, KB McCullough, KY Meyer, GS AF Mort, Elizabeth A. Demehin, Akinluwa A. Marple, Keith B. McCullough, Kathryn Y. Meyer, Gregg S. TI Setting Quality and Safety Priorities in a Target-Rich Environment: An Academic Medical Center's Challenge SO ACADEMIC MEDICINE LA English DT Article ID CARE AB Hospitals are continually challenged to provide safer and higher-quality patient care despite resource constraints. With an ever-increasing range of quality and safety targets at the national, state, and local levels, prioritization is crucial in effective institutional quality goal setting and resource allocation. Organizational goal-setting theory is a performance improvement methodology with strong results across many industries. The authors describe a structured goal-setting process they have established at Massachusetts General Hospital for setting annual institutional quality and safety goals. Begun in 2008, this process has been conducted on an annual basis. Quality and safety data are gathered from many sources, both internal and external to the hospital. These data are collated and classified, and multiple approaches are used to identify the most pressing quality issues facing the institution. The conclusions are subject to stringent internal review, and then the top quality goals of the institution are chosen. Specific tactical initiatives and executive owners are assigned to each goal, and metrics are selected to track performance. A reporting tool based on these tactics and metrics is used to deliver progress updates to senior hospital leadership. The hospital has experienced excellent results and strong organizational buy-in using this effective, low-cost, and replicable goal-setting process. It has led to improvements in structural, process, and outcomes aspects of quality. C1 [Mort, Elizabeth A.; Marple, Keith B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mort, Elizabeth A.] Massachusetts Gen Phys Org, Boston, MA USA. [Mort, Elizabeth A.] Partners Healthcare, Boston, MA USA. [Demehin, Akinluwa A.] Amer Hosp Assoc, Washington, DC USA. [McCullough, Kathryn Y.] Massachusetts Gen Hosp Phys Org, Vasc Ultrasound Core Lab, Boston, MA USA. [Meyer, Gregg S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Mort, EA (reprint author), Massachusetts Gen Hosp, Bulfinch 270,55 Fruit St, Boston, MA 02114 USA. EM emort@partners.org NR 20 TC 1 Z9 1 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD AUG PY 2013 VL 88 IS 8 BP 1099 EP 1104 DI 10.1097/ACM.0b013e31829a3ee8 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 235FO UT WOS:000325702400023 PM 23807111 ER PT J AU Wanderer, JP Leffert, LR Mhyre, JM Kuklina, EV Callaghan, WM Bateman, BT AF Wanderer, Jonathan P. Leffert, Lisa R. Mhyre, Jill M. Kuklina, Elena V. Callaghan, William M. Bateman, Brian T. TI Epidemiology of Obstetric-Related ICU Admissions in Maryland: 1999-2008 SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; intensive care; maternal health; maternal health services; maternal mortality ID INTENSIVE-CARE-UNIT; RISK-FACTORS; PREGNANCY; OUTCOMES; STATES; MORBIDITY; MORTALITY; DELIVERY; TRENDS; HOSPITALIZATIONS AB Objective: To define the prevalence, indications, and temporal trends in obstetric-related ICU admissions. Design: Descriptive analysis of utilization patterns. Setting: All hospitals within the state of Maryland. Patients: All antepartum, delivery, and postpartum patients who were hospitalized between 1999 and 2008. Interventions: None. Measurements and Main Results: We identified 2,927 ICU admissions from 765,598 admissions for antepartum, delivery, or postpartum conditions using appropriate International Classification of Diseases, 9th Revision, Clinical Modification codes. The overall rate of ICU utilization was 419.1 per 100,000 deliveries, with rates of 162.5, 202.6, and 54.0 per 100,000 deliveries for the antepartum, delivery, and postpartum periods, respectively. The leading diagnoses associated with ICU admission were pregnancy-related hypertensive disease (present in 29.9% of admissions), hemorrhage (18.8%), cardiomyopathy or other cardiac disease (18.3%), genitourinary infection (11.5%), complications from ectopic pregnancies and abortions (10.3%), nongenitourinary infection (10.1%), sepsis (7.1%), cerebrovascular disease (5.8%), and pulmonary embolism (3.7%). We assessed for changes in the most common diagnoses in the ICU population over time and found rising rates of sepsis (10.1 per 100,000 deliveries to 16.6 per 100,000 deliveries, p = 0.003) and trauma (9.2 per 100,000 deliveries to 13.6 per 100,000 deliveries, p = 0.026) with decreasing rates of anesthetic complications (11.3 per 100,000 to 4.7 per 100,000, p = 0.006). The overall frequency of obstetric-related ICU admission and the rates for other indications remained relatively stable. Conclusions: Between 1999 and 2008, 419.1 per 100,000 deliveries in Maryland were complicated by ICU admission. Hospitals providing obstetric services should plan for appropriate critical care management and/or transfer of women with severe morbidities during pregnancy. C1 [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Anesthesia, Nashville, TN 37235 USA. [Leffert, Lisa R.; Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Mhyre, Jill M.] Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI USA. [Kuklina, Elena V.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Washington, DC USA. [Callaghan, William M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Washington, DC USA. RP Wanderer, JP (reprint author), Vanderbilt Univ, Dept Anesthesia, 221 Kirkland Hall, Nashville, TN 37235 USA. EM jonathan.p.wanderer@vanderbilt.edu FU Massachusetts General Hospital; National Institute of Health [GM007592]; NY PGA 66th Assembly; NIH FX Supported, in part, by Massachusetts General Hospital departmental and National Institute of Health funds (BTB, grant GM007592).; Dr. Mhyre has received royalties from Chestnut Principles and Practices of Anesthesia, 5th Ed; payment for development of educational presentations from NY PGA 66th Assembly; travel/accommodations from ACOG Maternal Mortality Expert Panel, Joint Commission Panel on High Risk Pregnancy. Dr. Bateman received funding from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 32 TC 26 Z9 30 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 2013 VL 41 IS 8 BP 1844 EP 1852 DI 10.1097/CCM.0b013e31828a3e24 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 235FH UT WOS:000325701500017 PM 23648568 ER PT J AU Elmer, J Hou, P Wilcox, SR Chang, YC Schreiber, H Okechukwu, I Pontes-Neto, O Bajwa, E Hess, DR Avery, L Duran-Mendicuti, MA Camargo, CA Greenberg, SM Rosand, J Pallin, DJ Goldstein, JN AF Elmer, Jonathan Hou, Peter Wilcox, Susan R. Chang, Yuchiao Schreiber, Hannah Okechukwu, Ikenna Pontes-Neto, Octavio Bajwa, Ednan Hess, Dean R. Avery, Laura Duran-Mendicuti, Maria Alejandra Camargo, Carlos A., Jr. Greenberg, Steven M. Rosand, Jonathan Pallin, Daniel J. Goldstein, Joshua N. TI Acute Respiratory Distress Syndrome After Spontaneous Intracerebral Hemorrhage SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; hemorrhagic stroke; mechanical ventilation; tidal volume; ventilator-induced lung injury ID ACUTE LUNG INJURY; NEUROGENIC PULMONARY-EDEMA; INTENSIVE-CARE-UNIT; GLASGOW COMA SCALE; SUBARACHNOID HEMORRHAGE; MECHANICAL VENTILATION; HEMATOMA EXPANSION; SEVERE SEPSIS; TIDAL VOLUME; BRAIN-INJURY AB Objectives: Acute respiratory distress syndrome develops commonly in critically ill patients in response to an injurious stimulus. The prevalence and risk factors for development of acute respiratory distress syndrome after spontaneous intracerebral hemorrhage have not been reported. We sought to determine the prevalence of acute respiratory distress syndrome after intracerebral hemorrhage, characterize risk factors for its development, and assess its impact on patient outcomes. Design: Retrospective cohort study at two academic centers. Patients: We included consecutive patients presenting from June 1, 2000, to November 1, 2010, with intracerebral hemorrhage requiring mechanical ventilation. We excluded patients with age less than 18 years, intracerebral hemorrhage secondary to trauma, tumor, ischemic stroke, or structural lesion; if they required intubation only during surgery; if they were admitted for comfort measures; or for a history of immunodeficiency. Interventions: None. Measurements and Main Results: Data were collected both prospectively as part of an ongoing cohort study and by retrospective chart review. Of 1,665 patients identified by database query, 697 met inclusion criteria. The prevalence of acute respiratory distress syndrome was 27%. In unadjusted analysis, high tidal volume ventilation was associated with an increased risk of acute respiratory distress syndrome (hazard ratio, 1.79 [95% CI, 1.13-2.83]), as were male sex, RBC and plasma transfusion, higher fluid balance, obesity, hypoxemia, acidosis, tobacco use, emergent hematoma evacuation, and vasopressor dependence. In multivariable modeling, high tidal volume ventilation was the strongest risk factor for acute respiratory distress syndrome development (hazard ratio, 1.74 [95% CI, 1.08-2.81]) and for inhospital mortality (hazard ratio, 2.52 [95% CI, 1.46-4.34]). Conclusions: Development of acute respiratory distress syndrome is common after intubation for intracerebral hemorrhage. Modifiable risk factors, including high tidal volume ventilation, are associated with its development and in-patient mortality. C1 [Elmer, Jonathan] Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA 15260 USA. [Hou, Peter; Schreiber, Hannah; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Hou, Peter] Brigham & Womens Hosp, Dept Surg, Div Burn Trauma & Surg Crit Care, Boston, MA 02115 USA. [Hou, Peter; Wilcox, Susan R.; Chang, Yuchiao; Bajwa, Ednan; Hess, Dean R.; Avery, Laura; Duran-Mendicuti, Maria Alejandra; Camargo, Carlos A., Jr.; Greenberg, Steven M.; Rosand, Jonathan; Pallin, Daniel J.; Goldstein, Joshua N.] Harvard Univ, Sch Med, Boston, MA USA. [Wilcox, Susan R.; Okechukwu, Ikenna; Camargo, Carlos A., Jr.; Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pontes-Neto, Octavio; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bajwa, Ednan] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Avery, Laura] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Duran-Mendicuti, Maria Alejandra] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Rosand, Jonathan; Goldstein, Joshua N.] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Elmer, J (reprint author), Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Pittsburgh, PA 15260 USA. EM elmerjp@upmc.edu RI Pontes-Neto, Octavio/G-4294-2012; Pallin, Daniel/H-6382-2013; Goldstein, Joshua/H-8953-2016; OI Pontes-Neto, Octavio/0000-0003-0317-843X; Pallin, Daniel/0000-0002-8517-9702; Wilcox, Susan/0000-0001-7477-7531 FU Emergency Medicine Foundation/Emergency Medicine Resident's Association; Wuerz Award from the Department of Emergency Medicine at Brigham and Women's Hospital; National Institutes of Health [R01NS073344, R01NS059727, 5K23NS059774]; U of Texas-Grand Rounds [5R01AG026484-08, 5R01NS070834-03]; National Institutes of Health; Mass Medical Society; NINDS FX Supported, in part, by a grant from the Emergency Medicine Foundation/Emergency Medicine Resident's Association, the Wuerz Award from the Department of Emergency Medicine at Brigham and Women's Hospital, and by the National Institutes of Health (R01NS073344, R01NS059727, and 5K23NS059774).; Dr. Hess has consulted for Philips Respironics, ResMed, Breathe Technology, and Pari. Dr. Greenberg has consulted for Hoffman La-Roche, received grants 5R01AG026484-08 and 5R01NS070834-03, and received payment for lectures from U of Texas-Grand Rounds. Dr. Rosand has received grant support from the National Institutes of Health. Dr. Goldstein has received grant support from the Mass Medical Society, the National Institutes of Health and NINDS. He has consulted for CSL Behring. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 54 TC 19 Z9 20 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 2013 VL 41 IS 8 BP 1992 EP 2001 DI 10.1097/CCM.0b013e31828a3f4d PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 235FH UT WOS:000325701500034 PM 23760151 ER PT J AU Lien, S Verreault, DJ Alston, TA AF Lien, Susan Verreault, David J. Alston, Theodore A. TI Sustained airway pressure after transient occlusion of a valve venting a self-inflating manual resuscitator SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter C1 [Lien, Susan] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lien, S (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM talston@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 2013 VL 25 IS 5 BP 424 EP 425 DI 10.1016/j.jclinane.2013.02.008 PG 2 WC Anesthesiology SC Anesthesiology GA 235PJ UT WOS:000325732900015 PM 23965202 ER PT J AU Kao, SY Kempfle, JS Jensen, JB Perez-Fernandez, D Lysaght, AC Edge, AS Stankovic, KM AF Kao, Shyan-Yuan Kempfle, Judith S. Jensen, Jane B. Perez-Fernandez, Deborah Lysaght, Andrew C. Edge, Albert S. Stankovic, Konstantina M. TI Loss of osteoprotegerin expression in the inner ear causes degeneration of the cochlear nerve and sensorineural hearing loss SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Osteoprotegerin; Spiral ganglion cells; Cochlear neurons; Sensorineural hearing loss; Auditory stem cell ID SPIRAL GANGLION NEURONS; PAGETS-DISEASE; OTIC CAPSULE; CELL-DEATH; STEM-CELLS; TEMPORAL BONE; MICE; OSTEOPOROSIS; OTOSCLEROSIS; ERK AB Osteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations and variations in the OPG gene cause many human diseases that are characterized by not only skeletal abnormalities but also poorly understood hearing loss: Paget's disease, osteoporosis, and celiac disease. To gain insight into the mechanisms of hearing loss in OPG deficiency, we studied OPG knockout (Opg(-/-)) mice. We show that they develop sensorineural hearing loss, in addition to conductive hearing loss due to abnormal middle-ear bones. OPG deficiency caused demyelination and degeneration of the cochlear nerve in vivo. It also activated ERK, sensitized spiral ganglion cells (SGC) to apoptosis, and inhibited proliferation and survival of cochlear stem cells in vitro, which could be rescued by treatment with exogenous OPG, an ERK inhibitor, or bisphosphonate. Our results demonstrate a novel role for OPG in the regulation of SGC survival, and suggest a mechanism for sensorineural hearing loss in OPG deficiency. (c) 2013 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Konstantina_stankovic@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders [NIH-NIDCD K08 DC010419]; Massachusetts Life Sciences Center; Boston Foundation; Bertarelli Foundation FX This work was supported by grants from the National Institute on Deafness and Other Communication Disorders (NIH-NIDCD K08 DC010419), the Massachusetts Life Sciences Center, the Boston Foundation and the Bertarelli Foundation to K.M.S. We thank Drs. Charles Liberman and Gabriel Corfas for helpful comments. NR 47 TC 10 Z9 10 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2013 VL 56 BP 25 EP 33 DI 10.1016/j.nbd.2013.04.008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 210RX UT WOS:000323853300004 PM 23607938 ER PT J AU Yu, ZY Liu, N Li, YD Xu, JF Wang, XY AF Yu, Zhanyang Liu, Ning Li, Yadan Xu, Jianfeng Wang, Xiaoying TI Neuroglobin overexpression inhibits oxygen-glucose deprivation-induced mitochondrial permeability transition pore opening in primary cultured mouse cortical neurons SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Neuroglobin; Oxygen/glucose deprivation; Mitochondria permeability transition pore (mPTP); NAD(+) release; Mitochondria swelling; Cytochrome c ID DEPENDENT ANION CHANNEL; FOCAL CEREBRAL-ISCHEMIA; CELL-DEATH; CYCLOSPORINE-A; CYCLOPHILIN-D; CYTOCHROME-C; ENDOGENOUS NEUROPROTECTANT; HIPPOCAMPAL-NEURONS; REPERFUSION INJURY; IN-VITRO AB Neuroglobin (Ngb) is an endogenous neuroprotective molecule against hypoxic/ischemic brain injury, but the underlying mechanisms remain largely undefined. Our recent study revealed that Ngb can bind to voltage-dependent anion channel (VDAC), a regulator of mitochondria permeability transition (MPT). In this study we examined the role of Ngb in MPT pore (mPTP) opening following oxygen-glucose deprivation (OGD) in primary cultured mouse cortical neurons. Co-immunoprecipitation (Co-IP) and immunocytochemistry showed that the binding between Ngb and VDAC was increased after OGD compared to normoxia, indicating the OGD-enhanced Ngb-VDAC interaction. Ngb overexpression protected primary mouse cortical neurons from OGD-induced neuronal death, to an extent comparable to mPTP opening inhibitor, cyclosporine A (CsA) pretreatment. We further measured the role of Ngb in OGD-induced mPTP opening using Ngb overexpression and knockdown approaches in primary cultured neurons, and recombinant Ngb exposure to isolated mitochondria. Same as CsA pretreatment, Ngb overexpression significantly reduced OGD-induced mPTP opening markers including mitochondria swelling, mitochondrial NAD(+) release, and cytochrome c (Cyt c) release in primary cultured neurons. Recombinant Ngb incubation significantly reduced OGD-induced NAD(+) release and Cyt c release from isolated mitochondria. In contrast, Ngb knockdown significantly increased OGD-induced neuron death, and increased OGD-induced mitochondrial NAD(+) release and Cyt c release as well, and these outcomes could be rescued by CsA pretreatment In summary, our results demonstrated that Ngb overexpression can inhibit OGD-induced mPTP opening in primary cultured mouse cortical neurons, which may be one of the molecular mechanisms of Ngb's neuroprotection. (c) 2013 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. RP Yu, ZY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, 149 13th St,Room 2401, Charlestown, MA 02129 USA. EM zyu@partners.org; wangxi@helix.mgh.harvard.edu FU NIH [R01-NS049476]; American Heart Association [12POST9720007] FX This work was supported in part by NIH grant R01-NS049476 (to X.W.) and postdoctoral fellowship (12POST9720007) from the American Heart Association (to Z.Y.). We thank Ms. Jessica Poppe for language editorial assistance. We appreciate Dr. Eng H. Lo for his very helpful discussion. The authors declare no conflict of interest. NR 53 TC 27 Z9 27 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2013 VL 56 BP 95 EP 103 DI 10.1016/j.nbd.2013.04.015 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 210RX UT WOS:000323853300011 PM 23639789 ER PT J AU Potter, WB Basu, T O'Riordan, KJ Kirchner, A Rutecki, P Burger, C Roopra, A AF Potter, Wyatt B. Basu, Trina O'Riordan, Kenneth J. Kirchner, Allison Rutecki, Paul Burger, Corinna Roopra, Avtar TI Reduced Juvenile Long-Term Depression in Tuberous Sclerosis Complex Is Mitigated in Adults by Compensatory Recruitment of mGluR5 and Erk Signaling SO PLOS BIOLOGY LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; TEMPORAL-LOBE EPILEPSY; FRAGILE-X-SYNDROME; TUMOR-SUPPRESSOR COMPLEX; INITIATION-FACTOR 4E; MAMMALIAN TARGET; MOUSE MODEL; PROTEIN-SYNTHESIS; 3-KINASE/AKT PATHWAY; SYNAPTIC PLASTICITY AB Tuberous sclerosis complex (TSC) is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR) pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD) was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/-) CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/-) hippocampal slices. We also report that adult TSC2(+/-) mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC. C1 [Potter, Wyatt B.; Basu, Trina; Kirchner, Allison; Roopra, Avtar] Univ Wisconsin, Med Sci Ctr, Dept Neurosci, Madison, WI USA. [Potter, Wyatt B.; Basu, Trina] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [O'Riordan, Kenneth J.; Rutecki, Paul; Burger, Corinna] Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Dept Neurol, Madison, WI USA. [O'Riordan, Kenneth J.; Rutecki, Paul; Burger, Corinna] Univ Wisconsin, Madison, WI USA. RP Potter, WB (reprint author), Univ Wisconsin, Med Sci Ctr, Dept Neurosci, Madison, WI USA. EM asroopra@wisc.edu OI Burger, Corinna/0000-0002-9432-0114; O'Riordan, Kenneth J/0000-0003-0081-6010 FU Neuroscience Training Program [NIH/NIGMS T32GM007507]; Epilepsy Foundation individual pre-doctoral fellowship; CURE Multidisciplinary Award; NIH/NINDS [RO1NS065067] FX Neuroscience Training Program grant NIH/NIGMS T32GM007507. WBP was supported by an Epilepsy Foundation individual pre-doctoral fellowship. CURE Multidisciplinary Award to AR, CB, and PR. NIH/NINDS RO1NS065067 to AR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 9 Z9 10 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD AUG PY 2013 VL 11 IS 8 AR e1001627 DI 10.1371/journal.pbio.1001627 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 209PR UT WOS:000323771900008 PM 23966835 ER PT J AU Scirica, BM Kadakia, MB de Lemos, JA Roe, MT Morrow, DA Li, S Wiviott, SD Kontos, MC AF Scirica, Benjamin M. Kadakia, Mitul B. de Lemos, James A. Roe, Matthew T. Morrow, David A. Li, Shuang Wiviott, Stephen D. Kontos, Michael C. CA Natl Cardiovasc Data Registry TI Association between Natriuretic Peptides and Mortality among Patients Admitted with Myocardial Infarction: A Report from the ACTION Registry (R)-GWTG (TM) SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE CORONARY SYNDROMES; INTERVENTION OUTCOMES NETWORK; PROGNOSTIC VALUE; ARTERY-DISEASE; RISK SCORE; TROPONIN-T; BIOMARKERS; PERFORMANCE; REGISTRY; ASSAYS AB BACKGROUND: Patients with increased blood concentrations of natriuretic peptides (NPs) have poor cardiovascular outcomes after myocardial infarction (MI). The objectives of this analysis were to evaluate the utilization and the prognostic value of NP in a large, real-world MI cohort. METHODS: Data from 41 683 patients with non-ST-segment elevation MI (NSTEMI) and 27 860 patients with ST-segment elevation MI (STEMI) at 309 US hospitals were collected as part of the ACTION Registry (R)-GWTG (TM) (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines) (AR-G) between July 2008 and September 2009. RESULTS: B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) was measured in 19 528 (47%) of NSTEMI and 9220 (33%) of STEMI patients. Patients in whom NPs were measured were older and had more comorbidities, including prior heart failure or MI. There was a stepwise increase in the risk of in-hospital mortality with increasing BNP quartiles for both NSTEMI (1.3% vs 3.2% vs 5.8% vs 11.1%) and STEMI (1.9% vs 3.9% vs 8.2% vs 17.9%). The addition of BNP to the AR-G clinical model improved the C statistic from 0.796 to 0.807 (P < 0.001) for NSTEMI and from 0.848 to 0.855 (P < 0.003) for STEMI. The relationship between NPs and mortality was similar in patients without a history of heart failure or cardiogenic shock on presentation and in patients with preserved left ventricular function. CONCLUSIONS: NPs are measured in almost 50% of patients in the US admitted with MI and appear to be used in patients with more comorbidities. Higher NP concentrations were strongly and independently associated with in-hospital mortality in the almost 30 000 patients in whom NPs were assessed, including patients without heart failure. (c) 2013 American Association for Clinical Chemistry C1 [Scirica, Benjamin M.; Morrow, David A.; Wiviott, Stephen D.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. [Scirica, Benjamin M.; Morrow, David A.; Wiviott, Stephen D.] Harvard Univ, Sch Med, Boston, MA USA. [Kadakia, Mitul B.] Hosp Univ Penn, Cardiovasc Div, Philadelphia, PA 19104 USA. [de Lemos, James A.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Roe, Matthew T.; Li, Shuang] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Roe, Matthew T.; Li, Shuang] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Kontos, Michael C.] Virginia Commonwealth Univ, Pauley Heart Ctr, Div Cardiol, Richmond, VA USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; Genentech; Schering-Plough Corporation; Abbott; AstraZeneca; Amgen; Bayer Healthcare; Bristol-Myers Squibb; Daichii Sankyo; Eli Lilly; Gilead; GlaxoSmithKline; Merck (SPRI); Novartis; Pfizer; Roche Diagnostics; sanofi-aventis; Johnson Johnson; Alere, Inc.; Abbott Diagnostics; American College of Cardiology; Eisai FX The NCDR (R) ACTION Registry (R)-GWTG (TM) is administered by the American College of Cardiology Foundation (ACCF) and sponsored by Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Genentech, and Schering-Plough Corporation, who provide material support for the operation of the data collection and infrastructure. B.M. Scirica and D.A. Morrow, The TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, has received research grants from Abbott, AstraZeneca, Amgen, Bayer Healthcare, Bristol-Myers Squibb, Daichii Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Merck (SPRI), Novartis, Pfizer, Roche Diagnostics, sanofi-aventis, and Johnson & Johnson. J.A. de Lemos, Alere, Inc., Roche Diagnostics, and Abbott Diagnostics; M.T. Roe, American College of Cardiology; S.D. Wiviott, Eli Lilly, Daiichi Sankyo, AstraZeneca, Bristol Myers Squibb, and Eisai; M.C. Kontos, Research Astellas. NR 25 TC 7 Z9 8 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD AUG PY 2013 VL 59 IS 8 BP 1205 EP 1214 DI 10.1373/clinchem.2012.198556 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 231EW UT WOS:000325398100012 PM 23630179 ER PT J AU Amri, R Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI Impact of Screening Colonoscopy on Outcomes in Colon Cancer Surgery SO JAMA SURGERY LA English DT Article ID COLORECTAL-CANCER; ADENOMAS AB IMPORTANCE Screening colonoscopy seemingly decreases colorectal cancer rates in the United States. In addition to removing benign lesions and preventing progression to malignancy, screening colonoscopy theoretically identifies asymptomatic patients with early-stage disease, potentially leading to higher survival rates. OBJECTIVES To assess the effect of screening colonoscopy on outcomes of colon cancer surgery by reviewing differences in staging, disease-free interval, risk of recurrence, and survival and to identify whether diagnosis through screening improves long-term outcomes independent of staging. DESIGN Retrospective review of prospectively maintained, institutional review board-approved database. SETTING Tertiary care center with high patient volume. PATIENTS All patients who underwent colon cancer surgery at Massachusetts General Hospital from January 1, 2004, through December 31, 2011. INTERVENTION Colon cancer surgery. MAIN OUTCOMES AND MEASURES Postoperative staging, death, and recurrence, measured as incidence and time to event. RESULTS A total of 1071 patients were included, with 217 diagnosed through screening. Patients not diagnosed through screening were at risk for a more invasive tumor (>= T3: relative risk [RR] = 1.96; P < .001), nodal disease (RR = 1.92; P < .001), and metastatic disease on presentation (RR = 3.37; P < .001). In follow-up, these patients had higher death rates (RR = 3.02; P < .001) and recurrence rates (RR = 2.19; P = .004) as well as shorter survival (P < .001) and disease-free intervals (P < .001). Cox and logistic regression controlling for staging and baseline characteristics revealed that death rate (P = .02) and survival duration (P = .01) were better stage for stage with diagnosis through screening. Death and metastasis rates also remained significantly lower in tumors without nodal or metastatic spread (all P < .001). CONCLUSIONS AND RELEVANCE Patients with colon cancer identified on screening colonoscopy not only have lower-stage disease on presentation but also have better outcomes independent of their staging. Compliance to screening colonoscopy guidelines can play an important role in prolonging longevity, improving quality of life, and reducing health care costs through early detection of colon cancer. C1 [Berger, David L.] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM berger.david@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU Harvard Catalyst/The Harvard Clinical and Translational Science Center from the National Center for Research Resources and National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170- 05]; Dutch Cancer Society; Dutch Digestive Society; Amsterdam University Funds; Fulbright Foundation FX This work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (grant 8UL1TR000170- 05 from the National Center for Research Resources and National Center for Advancing Translational Sciences, National Institutes of Health and financial contributions from Harvard University and its affiliated academic health care centers). This work was also supported by the Dutch Cancer Society, the Dutch Digestive Society, the Amsterdam University Funds, and the Fulbright Foundation. NR 10 TC 21 Z9 21 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6254 J9 JAMA SURG JI JAMA Surg. PD AUG PY 2013 VL 148 IS 8 BP 747 EP 754 DI 10.1001/jamasurg.2013.8 PG 8 WC Surgery SC Surgery GA 206XB UT WOS:000323558100013 PM 23784448 ER PT J AU Chiyomaru, T Yamamura, S Fukuhara, S Yoshino, H Kinoshita, T Majid, S Saini, S Chang, I Tanaka, Y Enokida, H Seki, N Nakagawa, M Dahiya, R AF Chiyomaru, Takeshi Yamamura, Soichiro Fukuhara, Shinichiro Yoshino, Hirofumi Kinoshita, Takashi Majid, Shahana Saini, Sharanjot Chang, Inik Tanaka, Yuichiro Enokida, Hideki Seki, Naohiko Nakagawa, Masayuki Dahiya, Rajvir TI Genistein Inhibits Prostate Cancer Cell Growth by Targeting miR-34a and Oncogenic HOTAIR SO PLOS ONE LA English DT Article ID LONG NONCODING RNA; HEPATOCELLULAR-CARCINOMA; SIGNALING PATHWAYS; EXPRESSION; BETA; MICRORNA-27A; PROGRESSION; SOX17; RISK AB Objective: Genistein is a soy isoflavone that has antitumor activity both in vitro and in vivo. It has been shown that genistein inhibits many type of cancers including prostate cancer (PCa) by regulating several cell signaling pathways and microRNAs (miRNAs). Recent studies suggest that the long non-coding RNAs (lncRNAs) are also involved in many cellular processes. At present there are no reports about the relationship between gensitein, miRNAs and lncRNAs. In this study, we focused on miRNAs, lncRNA that are regulated by genistein and investigated their functional role in PCa. Method: Microarray (SurePrint G3 Human GE 8x60K) was used for expression profiling of genistein treated and control PCa cells (PC3 and DU145). Functional assay (cell proliferation, migration, invasion, apoptosis and cell cycle assays) were performed with the PCa cell lines, PC3 and DU145. Both in vitro and in vivo (nude mouse) models were used for growth assays. Luciferase reporter assays were used for binding of miR-34a to HOTAIR. Results: LncRNA profiling showed that HOTAIR was highly regulated by genistein and its expression was higher in castration-resistant PCa cell lines than in normal prostate cells. Knockdown (siRNA) of HOTAIR decreased PCa cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. miR-34a was also up-regulated by genistein and may directly target HOTAIR in both PC3 and DU145 PCa cells. Conclusions: Our results indicated that genistein inhibited PCa cell growth through down-regulation of oncogenic HOTAIR that is also targeted by tumor suppressor miR-34a. These findings enhance understanding of how genistein regulates lncRNA HOTAIR and miR-34a in PCa. C1 [Chiyomaru, Takeshi; Yamamura, Soichiro; Fukuhara, Shinichiro; Majid, Shahana; Saini, Sharanjot; Chang, Inik; Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Chiyomaru, Takeshi; Yamamura, Soichiro; Fukuhara, Shinichiro; Majid, Shahana; Saini, Sharanjot; Chang, Inik; Tanaka, Yuichiro; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yoshino, Hirofumi; Enokida, Hideki] Kagoshima Univ, Dept Urol, Grad Sch Med & Dent Sci, Kagoshima 890, Japan. [Kinoshita, Takashi; Seki, Naohiko; Nakagawa, Masayuki] Chiba Univ, Dept Funct Genom, Grad Sch Med, Chiba, Japan. RP Dahiya, R (reprint author), San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. EM rdahiya@urology.ucsf.edu FU National Center for Research Resources of the National Institutes of Health [R01CA160079, R01CA138642, T32DK007790]; VA Merit Review and VA Program Project FX This research was supported by the National Center for Research Resources of the National Institutes of Health through Grant Number R01CA160079, R01CA138642, T32DK007790 and VA Merit Review and VA Program Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 66 Z9 71 U1 1 U2 24 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 1 PY 2013 VL 8 IS 8 AR e70372 DI 10.1371/journal.pone.0070372 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219PB UT WOS:000324518400062 PM 23936419 ER PT J AU Hunter, RM Davie, C Rudd, A Thompson, A Walker, H Thomson, N Mountford, J Schwamm, L Deanfield, J Thompson, K Dewan, B Mistry, M Quoraishi, S Morris, S AF Hunter, Rachael Maree Davie, Charles Rudd, Anthony Thompson, Alan Walker, Hilary Thomson, Neil Mountford, James Schwamm, Lee Deanfield, John Thompson, Kerry Dewan, Bikash Mistry, Minesh Quoraishi, Sadik Morris, Stephen TI Impact on Clinical and Cost Outcomes of a Centralized Approach to Acute Stroke Care in London: A Comparative Effectiveness Before and After Model SO PLOS ONE LA English DT Article AB Background: In July 2010 a new multiple hub-and-spoke model for acute stroke care was implemented across the whole of London, UK, with continuous specialist care during the first 72 hours provided at 8 hyper-acute stroke units (HASUs) compared to the previous model of 30 local hospitals receiving acute stroke patients. We investigated differences in clinical outcomes and costs between the new and old models. Methods: We compared outcomes and costs 'before' (July 2007-July 2008) vs. 'after' (July 2010-June 2011) the introduction of the new model, adjusted for patient characteristics and national time trends in mortality and length of stay. We constructed 90-day and 10-year decision analytic models using data from population based stroke registers, audits and published sources. Mortality and length of stay were modelled using survival analysis. Findings: In a pooled sample of 307 patients 'before' and 3156 patients 'after', survival improved in the 'after' period (age adjusted hazard ratio 0.54; 95% CI 0.41-0.72). The predicted survival rates at 90 days in the deterministic model adjusted for national trends were 87.2% 'before' % (95% CI 86.7%-87.7%) and 88.7% 'after' (95% CI 88.6%-88.8%); a relative reduction in deaths of 12% (95% CI 8%-16%). Based on a cohort of 6,438 stroke patients, the model produces a total cost saving of 5.2 pound million per year at 90 days (95% CI 4.9- pound 5.5 pound million; 811 pound per patient). Conclusion: A centralized model for acute stroke care across an entire metropolitan city appears to have reduced mortality for a reduced cost per patient, predominately as a result of reduced hospital length of stay. C1 [Hunter, Rachael Maree] UCL, Res Dept Primary Care & Populat Hlth, London, England. [Davie, Charles; Thompson, Kerry; Dewan, Bikash] Royal Free London NHS Fdn Trust, Dept Clin Neurosci, London, England. [Rudd, Anthony] Kings Coll London, Div Hlth & Social Care Res, London, England. [Rudd, Anthony] Guys & St Thomas NHS Fdn Trust, Natl Inst Hlth Res, Comprehens Biomed Res Ctr, London, England. [Thompson, Alan] UCL, Inst Neurol, London, England. [Walker, Hilary] North Cent London CardioVasc & Stroke Network, London, England. [Thomson, Neil] London Ambulance Serv NHS Trust, London, England. [Mountford, James] UCLPartners, London, England. [Schwamm, Lee] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Deanfield, John] UCL, Ctr Cardiovasc Prevent & Outcomes, London, England. [Mistry, Minesh; Quoraishi, Sadik] UCL, UCL Med Sch, London, England. [Morris, Stephen] UCL, Dept Appl Hlth Res, London, England. RP Hunter, RM (reprint author), UCL, Res Dept Primary Care & Populat Hlth, London, England. EM r.hunter@ucl.ac.uk RI Thompson, Alan/C-2654-2008; OI Thompson, Alan/0000-0002-4333-8496; Schwamm, Lee/0000-0003-0592-9145 FU NHS London; National Institute for Health Research (NIHR) [RP-PG-0407-10184]; Department of Health's NIHR Biomedical Research Centres funding scheme FX The study was funded by NHS London. This study uses data obtained via independent research commissioned by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0407-10184). The views expressed are not necessarily those of the NHS, the NIHR or the Department of Health. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 21 Z9 21 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 1 PY 2013 VL 8 IS 8 AR e70420 DI 10.1371/journal.pone.0070420 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219PB UT WOS:000324518400066 PM 23936427 ER PT J AU Neufeld, T Ludwig, B Barkai, U Weir, GC Colton, CK Evron, Y Balyura, M Yavriyants, K Zimermann, B Azarov, D Maimon, S Shabtay, N Rozenshtein, T Lorber, D Steffen, A Willenz, U Bloch, K Vardi, P Taube, R de Vos, P Lewis, EC Bornstein, SR Rotem, A AF Neufeld, Tova Ludwig, Barbara Barkai, Uriel Weir, Gordon C. Colton, Clark K. Evron, Yoav Balyura, Maria Yavriyants, Karina Zimermann, Baruch Azarov, Dmitri Maimon, Shiri Shabtay, Noa Rozenshtein, Tania Lorber, Dana Steffen, Anja Willenz, Udi Bloch, Konstantine Vardi, Pnina Taube, Ran de Vos, Paul Lewis, Eli C. Bornstein, Stefan R. Rotem, Avi TI The Efficacy of an Immunoisolating Membrane System for Islet Xenotransplantation in Minipigs SO PLOS ONE LA English DT Article ID PIG ISLETS; EDMONTON PROTOCOL; PANCREATIC-ISLETS; BLOOD-FLOW; TRANSPLANTATION; PRIMATES; IMMUNOSUPPRESSION; SURVIVAL; MONKEYS; GROWTH AB Developing a device that protects xenogeneic islets to allow treatment and potentially cure of diabetes in large mammals has been a major challenge in the past decade. Using xenogeneic islets for transplantation is required in light of donor shortage and the large number of diabetic patients that qualify for islet transplantation. Until now, however, host immunoreactivity against the xenogeneic graft has been a major drawback for the use of porcine islets. Our study demonstrates the applicability of a novel immunoprotective membrane that allows successful xenotransplantation of rat islets in diabetic minipigs without immunosuppressive therapy. Rat pancreatic islets were encapsulated in highly purified alginate and integrated into a plastic macrochamber covered by a poly-membrane for subcutaneous transplantation. Diabetic Sinclair pigs were transplanted and followed for up to 90 days. We demonstrated a persistent graft function and restoration of normoglycemia without the need for immunosuppressive therapy. This concept could potentially offer an attractive strategy for a more widespread islet replacement therapy that would restore endogenous insulin secretion in diabetic patients without the need for immunosuppressive drugs and may even open up an avenue for safe utilization of xenogeneic islet donors. C1 [Neufeld, Tova; Evron, Yoav; Zimermann, Baruch; Azarov, Dmitri; Maimon, Shiri; Lorber, Dana; Rotem, Avi] Beta O2 Technol, Dept Technol, Rosh Haayin, Israel. [Ludwig, Barbara; Barkai, Uriel; Balyura, Maria; Steffen, Anja; Bornstein, Stefan R.] Univ Hosp Carl Gustav Carus, Dept Med 3, Dresden, Germany. [Barkai, Uriel; Balyura, Maria; Yavriyants, Karina; Shabtay, Noa; Rozenshtein, Tania] Beta O2 Technol, Islet Dept, Rosh Haayin, Israel. [Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Trasnplantat & Cell Biol, Boston, MA 02215 USA. [Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Willenz, Udi] Lahav Res Inst, Vet Dept, Lahav, Israel. [Bloch, Konstantine; Vardi, Pnina] Tel Aviv Univ, Fac Med, Diabet & Obes Res Lab, IL-49100 Petah Tiqwa, Israel. [Taube, Ran] Ben Gurion Univ Negev, Dept Microbiol Immunol & Genet, IL-84105 Beer Sheva, Israel. [de Vos, Paul] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Lab Med, NL-9713 AV Groningen, Netherlands. [Lewis, Eli C.] Ben Gurion Univ Negev, Dept Clin Biochem & Pharmacol, IL-84105 Beer Sheva, Israel. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Trasnplantat & Cell Biol, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu RI de Vos, Paul/A-3170-2013 FU Beta-O2; Deutsche Forschungsgemeinschaft [SFB TRR 127, BR 1179, KFO 252]; Dresden Centre of Excellence; Centre for Regenerative Therapies Dresden; Paul Langerhans Institute Dresden - The German Center for Diabetes Research FX This work was funded by Beta-O2 (http://www.beta-o2.com/), the Deutsche Forschungsgemeinschaft grants (http://www.dfg.de/en/) SFB TRR 127 "Biology of xenogeneic cell, tissue and organ transplantation" (to BL, SRB), BR 1179 (to BL), and KFO 252 (to BL, SRB), Dresden Centre of Excellence (http://ccoe-dresden.de/), Centre for Regenerative Therapies Dresden (http://www.crt-dresden.de/), Paul Langerhans Institute Dresden - The German Center for Diabetes Research (http://www.dzd-ev.de/en). The funders (except for Beta-O2) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Beta-O2 had a role in study design, data collection, and analysis. NR 28 TC 24 Z9 25 U1 3 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 1 PY 2013 VL 8 IS 8 AR e70150 DI 10.1371/journal.pone.0070150 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219PB UT WOS:000324518400039 PM 23936385 ER PT J AU Strangman, GE Li, Z Zhang, Q AF Strangman, Gary E. Li, Zhi Zhang, Quan TI Depth Sensitivity and Source-Detector Separations for Near Infrared Spectroscopy Based on the Colin27 Brain Template SO PLOS ONE LA English DT Article ID ADULT HEAD MODEL; LIGHT-PROPAGATION; PHOTON MIGRATION; SUPERFICIAL TISSUE; FREQUENCY-DOMAIN; THICKNESS; SCATTERING; TRANSPORT; SCALP; INTERFERENCE AB Understanding the spatial and depth sensitivity of non-invasive near-infrared spectroscopy (NIRS) measurements to brain tissue-i.e., near-infrared neuromonitoring (NIN) - is essential for designing experiments as well as interpreting research findings. However, a thorough characterization of such sensitivity in realistic head models has remained unavailable. In this study, we conducted 3,555 Monte Carlo (MC) simulations to densely cover the scalp of a well-characterized, adult male template brain (Colin27). We sought to evaluate: (i) the spatial sensitivity profile of NIRS to brain tissue as a function of source-detector separation, (ii) the NIRS sensitivity to brain tissue as a function of depth in this realistic and complex head model, and (iii) the effect of NIRS instrument sensitivity on detecting brain activation. We found that increasing the source-detector (SD) separation from 20 to 65 mm provides monotonic increases in sensitivity to brain tissue. For every 10 mm increase in SD separation (up to similar to 45 mm), sensitivity to gray matter increased an additional 4%. Our analyses also demonstrate that sensitivity in depth (S) decreases exponentially, with a "rule-of-thumb" formula S = 0.75*0.85(depth). Thus, while the depth sensitivity of NIRS is not strictly limited, NIN signals in adult humans are strongly biased towards the outermost 10-15 mm of intracranial space. These general results, along with the detailed quantitation of sensitivity estimates around the head, can provide detailed guidance for interpreting the likely sources of NIRS signals, as well as help NIRS investigators design and plan better NIRS experiments, head probes and instruments. C1 [Strangman, Gary E.; Li, Zhi; Zhang, Quan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. RP Strangman, GE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. EM strang@nmr.mgh.harvard.edu FU National Space Biomedical Research Institute through NASA [NCC 9-58] FX This work was supported by the National Space Biomedical Research Institute through NASA NCC 9-58. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 25 Z9 25 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 1 PY 2013 VL 8 IS 8 AR e66319 DI 10.1371/journal.pone.0066319 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219PB UT WOS:000324518400003 PM 23936292 ER PT J AU Bressani, AEL Mariath, AAS Haas, AN Garcia-Godoy, F de Araujo, FB AF Lemes Bressani, Ana Eliza Souza Mariath, Adriela Azevedo Haas, Alex Nogueira Garcia-Godoy, Franklin de Araujo, Fernando Borba TI Incomplete caries removal and indirect pulp capping in primary molars: A randomized controlled trial SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID DEEP CARIOUS LESIONS; MICROBIOLOGICAL VALIDATION; PRIMARY TEETH; MICROORGANISMS; DENTIN AB Purpose: To compare the effect of incomplete caries removal (ICR) and indirect pulp capping (IPC) with calcium hydroxide (CH) or an inert material (wax) on color, consistency and contamination of the remaining dentin of primary molars. Methods: This double-blind, parallel-design, randomized controlled trial included 30 children presenting one primary molar with deep caries lesion. Children were randomly assigned after ICR to receive IPC with CH or wax. All-teeth were then restored with resin composite. Baseline dentin color and consistency were evaluated after ICR, and dentin samples were collected for contamination analyses using scanning electron microscopy. After 3 months, restorations were removed and the three parameters were re-evaluated. In both groups, dentin became significantly darker after 3 months. Results: No cases of yellow dentin were observed after 3 months with CH compared to 33.3% of the wax cases (P< 0.05). A statistically significant difference over time was observed only for CH regarding consistency. CH stimulated a dentin hardening process in a statistically higher number of cases than wax (86.7% vs. 33.3%; P= 0.008). Contamination changed significantly over time in CH and wax without significant difference between groups. It was concluded that CH and wax arrested the carious process of the remaining carious dentin after indirect pulp capping, but CH showed superior dentin color and consistency after 3 months. C1 [Lemes Bressani, Ana Eliza; Souza Mariath, Adriela Azevedo; de Araujo, Fernando Borba] Univ Fed Rio Grande do Sul, Fac Dent, Dept Pediat Dent, Porto Alegre, RS, Brazil. [Haas, Alex Nogueira] Univ Fed Rio Grande do Sul, Fac Dent, Dept Periodontol, Porto Alegre, RS, Brazil. [Garcia-Godoy, Franklin] Univ Tennessee, Ctr Hlth Sci, Coll Dent, Biosci Res Ctr, Memphis, TN 38163 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Cambridge, MA USA. RP de Araujo, FB (reprint author), Rua Ramiro Barcelos 2492, BR-90035003 Porto Alegre, RS, Brazil. EM fernando.araujo@ufrgs.br OI Araujo, Fernando/0000-0001-6471-5564; Haas, Alex/0000-0003-0531-6234 NR 27 TC 2 Z9 2 U1 2 U2 11 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD AUG PY 2013 VL 26 IS 4 BP 196 EP 200 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 221KZ UT WOS:000324659100005 PM 24693629 ER PT J AU Welzel, TM Graubard, BI Quraishi, S Zeuzem, S Davila, JA El-Serag, HB McGlynn, KA AF Welzel, Tania M. Graubard, Barry I. Quraishi, Sabah Zeuzem, Stefan Davila, Jessica A. El-Serag, Hashem B. McGlynn, Katherine A. TI Population-Attributable Fractions of Risk Factors for Hepatocellular Carcinoma in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PRIMARY LIVER-CANCER; C VIRUS-INFECTION; NONALCOHOLIC STEATOHEPATITIS; DIABETES-MELLITUS; HEPATITIS-B; ALCOHOL; DISEASE; COHORT; EPIDEMIOLOGY; ASSOCIATION AB OBJECTIVES: Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States. METHODS: Persons >= 68 years diagnosed with HCC (n = 6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5 % random sample (n = 255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95 % confidence intervals (95 % CI) and PAFs were calculated. RESULTS: As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95 % CI: 36.29-43.84), HBV (OR 11.17, 95 % CI: 9.18-13.59), alcohol-related disorders (OR 4.06, 95 % CI: 3.82-4.32), rare metabolic disorders (OR 3.45, 95 % CI: 2.97-4.02), and diabetes and/or obesity (OR 2.47, 95 % CI: 2.34-2.61). The PAF of all factors combined was 64.5 % (males 65.6 %; females 62.2 %). The PAF was highest among Asians (70.1 %) and lowest among black persons (52.4 %). Among individual factors, diabetes/obesity had the greatest PAF (36.6 %), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%). CONCLUSIONS: The dominant risk factors for HCC in the United States among persons = 68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor. C1 [Welzel, Tania M.; Zeuzem, Stefan] Johann Wolfgang Goethe Univ Hosp, Frankfurt, Germany. [Graubard, Barry I.; Quraishi, Sabah; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Davila, Jessica A.; El-Serag, Hashem B.] Houston Vet Affairs Med Ctr, Houston, TX USA. [Davila, Jessica A.; El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. RP McGlynn, KA (reprint author), NCI, DCEG, NIH, EPS 5022,6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov FU Intramural Research Program of the National Cancer Institute, National Institutes of Health FX This work was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 32 TC 74 Z9 74 U1 0 U2 9 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 AUG PY 2013 VL 108 IS 8 BP 1314 EP 1321 DI 10.1038/ajg.2013.160 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 222BM UT WOS:000324704800013 PM 23752878 ER PT J AU Dominitz, JA Robertson, DJ AF Dominitz, Jason A. Robertson, Douglas J. TI Interval Cancers: Learning from the Past as We Build for the Future SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID SERVICES TASK-FORCE; COLORECTAL-CANCER; SCREENING COLONOSCOPY; ASYMPTOMATIC ADULTS; COST-EFFECTIVENESS; MISS RATE; RISK; PREDICTORS; RATIONALE; MORTALITY AB While colonoscopy is the gold standard for the evaluation of the colon, research on post-colonoscopy colorectal cancers has increased our awareness of its limitations. In this issue of the Journal, Erichsen et al. provide evidence to suggest that post-colonoscopy colorectal cancers are most likely due to missed cancers at the time of the index colonoscopy, rather than due to aggressive tumor biology. Ultimately, studies demonstrating the shortcomings of colonoscopy are a call to action for the gastroenterology community to develop strategies and new technologies to improve the effectiveness of colonoscopy. C1 [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Robertson, Douglas J.] Geisel Sch Med Dartmouth, White River Junct VA Med Ctr, White River Junction, VA USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 111 Gastro, Seattle, WA 98108 USA. EM jason.dominitz@va.gov OI Dominitz, Jason/0000-0002-8070-7086 NR 32 TC 2 Z9 2 U1 0 U2 2 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 AUG PY 2013 VL 108 IS 8 BP 1341 EP 1343 DI 10.1038/ajg.2013.177 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 222BM UT WOS:000324704800016 PM 23912407 ER PT J AU Tacheva-Grigorova, SK Santos, AJM Boucrot, E Kirchhausen, T AF Tacheva-Grigorova, Silvia K. Santos, Antonio J. M. Boucrot, Emmanuel Kirchhausen, Tom TI Clathrin-Mediated Endocytosis Persists during Unperturbed Mitosis SO CELL REPORTS LA English DT Article ID SURFACE FUNCTIONS; TRANSFERRIN RECEPTOR; COATED PITS; CELLS; INHIBITOR; INTERNALIZATION; PINOCYTOSIS; INTERPHASE; MICROSCOPY; CYCLE AB How does mitosis influence the critical process of endocytosis? Some experiments lead to the conclusion that endocytosis arrests completely during mitosis, whereas others indicate that endocytosis persists. We have resolved this apparent discrepancy by showing how conditions of the experiment influence its outcome. The dynamics of clathrincoated pit formation and the uptake of transferrin are maintained in naturally dividing cells but are nearly absent in mitotic cells arrested chemically by treatment with nocodazole, S-Trityl-L-cysteine, or RO-3306. Moreover, sequentially incubating cells at 4 degrees C and then shifting them to 37 degrees C or to serum starvation artificially increases the amount of transferrin receptor at the surface of naturally dividing cells, leading to the incorrect conclusion that endocytosis has ceased during mitosis. Thus, our data show that endocytosis is unaffected during all stages of natural cell division. C1 [Tacheva-Grigorova, Silvia K.; Kirchhausen, Tom] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Santos, Antonio J. M.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, Sect Microbiol, London SW7 2AZ, England. [Santos, Antonio J. M.] Univ Porto, Grad Program Areas Basic & Appl Biol GABBA, P-4099002 Oporto, Portugal. [Boucrot, Emmanuel] UCL, Div Biosci, Inst Struct & Mol Biol, London WC1E 6BT, England. [Kirchhausen, Tom] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. [Kirchhausen, Tom] Harvard Univ, Dept Pediat, Sch Med, Boston, MA 02115 USA. RP Boucrot, E (reprint author), UCL, Div Biosci, Inst Struct & Mol Biol, Mortimer St, London WC1E 6BT, England. EM e.boucrot@ucl.ac.uk; kirchhausen@crystal.harvard.edu OI Santos, Antonio/0000-0001-6514-7423 FU NIH [GM-075252, U54 AI057159]; Fundacao para a Ciencia e Tecnologia; Biological Sciences Research Council (BBSRC) FX We thank E. Marino for maintaining the imaging resources in the Kirchhausen laboratory and R. Massol for making IMAB available. This work was supported in part by NIH grants GM-075252 (to T. K.) and U54 AI057159 (New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility), the Fundacao para a Ciencia e Tecnologia (to A.J.M.S.), and a Biological Sciences Research Council (BBSRC) David Phillips Research Fellowship (to E.B.). NR 22 TC 15 Z9 15 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD AUG PY 2013 VL 4 IS 4 BP 659 EP 668 DI 10.1016/j.celrep.2013.07.017 PG 10 WC Cell Biology SC Cell Biology GA 216LU UT WOS:000324285700006 PM 23954786 ER PT J AU Grenon, NN AF Grenon, Nina N. TI Managing Toxicities Associated With Antiangiogenic Biologic Agents in Combination With Chemotherapy for Metastatic Colorectal Cancer SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID EVIDENCE-BASED INTERVENTIONS; PHASE-II TRIAL; CLINICAL-PRACTICE GUIDELINE; COOPERATIVE-ONCOLOGY-GROUP; PUTTING EVIDENCE; AMERICAN-SOCIETY; INFUSIONAL FLUOROURACIL; 1ST-LINE TREATMENT; RANDOMIZED-TRIAL; VEGF-TRAP AB Toxicities commonly associated with antiangiogenic agents include hypertension, proteinuria, wound-healing complications, bleeding or hemorrhage, thromboembolic events, hypersensitivity reactions, and gastrointestinal perforation; however, toxicities most often attributed to chemotherapy include nausea, vomiting, diarrhea, constipation, fatigue, neuropathy, mucositis, hand-foot syndrome, hypersensitivity reactions, and myelosuppression. Patients with metastatic colorectal cancer (mCRC) who receive an antiangiogenic agent in combination with chemotherapy may experience toxicities related to both chemotherapy and the antiangiogenic agent. If possible, evidence-based interventions should be used for the management of toxicities. Patient education about expected toxicities and optimal toxicity management can promote the optimal use of therapy to improve survival and quality of life. Oncology nurses are well positioned to educate patients and their families on anticipated treatment and management of side effects. This article summarizes the incidence of toxicities associated with the antiangiogenic biologic agents aflibercept and bevacizumab, in combination with chemotherapy for patients with mCRC, and provides strategies for managing these toxicities based on clinical practice guidelines. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Grenon, NN (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM nina_grenon@dfci.harvard.edu NR 56 TC 4 Z9 4 U1 1 U2 6 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD AUG PY 2013 VL 17 IS 4 BP 425 EP 433 DI 10.1188/13.CJON.425-433 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 220EE UT WOS:000324564000013 PM 23899982 ER PT J AU Friedlander, AH Aghazadehsanai, N Chang, TI Harada, N Garrett, NR AF Friedlander, A. H. Aghazadehsanai, N. Chang, T. I. Harada, N. Garrett, N. R. TI Prevalence of calcified carotid artery atheromas on panoramic images of individuals with primary hyperparathyroidism SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article DE primary hyperparathyroidism; atherosclerosis; carotid artery; panoramic images ID PARATHYROID-HORMONE; CARDIOVASCULAR RISK; RADIOGRAPHY; MORTALITY; POPULATION; DISEASE AB Objectives: Primary hyperparathyroidism (PHPT), affecting 1% of the population, is associated with increased cardiovascular morbidity and mortality. The presence of calcified carotid artery plaque (CCAP) on panoramic images is a validated risk indicator of future adverse cardiovascular events. We hypothesized that military veterans aged 50 years or older diagnosed with PHPT by increased parathyroid hormone and calcium levels would frequently have CCAP on their images. Methods: We determined the prevalence rates of CCAP on the images of patients diagnosed with PHPT and evaluated their atherogenic risk profiles, including hypertension, dyslipidaemia, diabetes and obesity. Comparisons of atherogenic risk factors were made between subjects with and without observed CCAP on their panoramic images. Results: Of the 60 patients (86.7% males and 13.3% females, mean age 73.2 +/- 11.3 years) with PHPT, 40% had atheromas. There were no significant differences between CCAP+ and CCAP- groups in gender or race (p > 0.05). The atherogenic profile (age, body mass index, hypertension, diabetes, hyperlipidaemia) in the CCAP+ and CCAP- groups was not significantly different (p > 0.05). Conclusions: Calcified carotid artery atheromas are often seen on the panoramic images of patients with PHPT. Thus, dentists must be uniquely vigilant for these lesions when evaluating these studies. C1 [Friedlander, A. H.; Aghazadehsanai, N.; Chang, T. I.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 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.; Chang, T. I.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Harada, N.] Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Member Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Harada, N.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Garrett, N. R.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov NR 26 TC 1 Z9 2 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD AUG PY 2013 VL 42 IS 8 AR 20130118 DI 10.1259/dmfr.20130118 PG 4 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA 223FA UT WOS:000324788900003 PM 23775925 ER PT J AU Salamone, JD Collins-Praino, LE Pardo, M Podurgiel, SJ Baqi, Y Muller, CE Schwarzschild, MA Correa, M AF Salamone, John D. Collins-Praino, Lyndsey E. Pardo, Marta Podurgiel, Samantha J. Baqi, Younis Mueller, Christa E. Schwarzschild, Michael A. Correa, Merce TI Conditional neural knockout of the adenosine A(2A) receptor and pharmacological A(2A) antagonism reduce pilocarpine-induced tremulous jaw movements: Studies with a mouse model of parkinsonian tremor SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Motor; Parkinson's disease; Parkinsonism; Striatum; Muscarinic receptor; Acetylcholine ID C-FOS EXPRESSION; ORAL TREMOR; RATS; DISEASE; MICE; ISTRADEFYLLINE; TROPICAMIDE; SYMPTOMS; AGONISTS; MOTOR AB Tremulous jaw movements are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rats, tremulous jaw movements can be induced by a number of conditions that parallel those seen in human parkinsonism, including dopamine depletion, dopamine antagonism, and cholinomimetic drugs. Moreover, tremulous jaw movements in rats can be attenuated using antiparkinsonian agents such as L-DOPA, dopamine agonists, muscarinic antagonists, and adenosine A(2A) antagonists. In the present studies, a mouse model of tremulous jaw movements was established to investigate the effects of adenosine A(2A) antagonism, and a conditional neuronal knockout of adenosine A(2A) receptors, on cholinomimetic-induced tremulous jaw movements. The muscarinic agonist pilocarpine significantly induced tremulous jaw movements in a dose-dependent manner (0.25-1.0 mg/kg IP). These movements occurred largely in the 3-7.5 Hz local frequency range. Administration of the adenosine A(2A) antagonist MSX-3 (2.5-10.0 mg/kg IP) significantly attenuated pilocarpine-induced tremulous jaw movements. Furthermore, adenosine A(2A) receptor knockout mice showed a significant reduction in pilocarpine-induced tremulous jaw movements compared to littermate controls. These results demonstrate the feasibility of using the tremulous jaw movement model in mice, and indicate that adenosine A(2A) receptor antagonism and deletion are capable of reducing cholinomimetic-induced tremulous jaw movements in mice. Future studies should investigate the effects of additional genetic manipulations using the mouse tremulous jaw movement model. (C) 2013 Elsevier B.V. and ECNP. All rights reserved. C1 [Salamone, John D.; Collins-Praino, Lyndsey E.; Pardo, Marta; Podurgiel, Samantha J.; Correa, Merce] Univ Connecticut, Dept Psychol, Behav Neurosci Div, Storrs, CT 06269 USA. [Pardo, Marta; Correa, Merce] Univ Jaume 1, Dept Psychobiol, Castellon de La Plana, Spain. [Baqi, Younis; Mueller, Christa E.] Univ Bonn, Inst Pharmazeut, Pharma Zentrum Bonn, Bonn, Germany. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Salamone, JD (reprint author), Univ Connecticut, Dept Psychol, Behav Neurosci Div, Storrs, CT 06269 USA. EM john.salamone@uconn.edu RI Salamone, John/H-8165-2015; CORREA, MERCE/G-6125-2011; Baqi, Younis/I-8240-2016; Muller, Christa/C-7748-2014 OI Salamone, John/0000-0001-6435-9635; CORREA, MERCE/0000-0002-9868-3131; Baqi, Younis/0000-0002-9659-8419; Muller, Christa/0000-0002-0013-6624 FU University of Connecticut Research Foundation; NIH [K24NS60991]; DoD [W81XWH-11-1-0150]; Fundacio Bancaixa-UJI [P1.1B2010-43]; Caja Navarra; Fundacio Bancaixa-UJI FX This work was supported by grants to John Salamone from the University of Connecticut Research Foundation, which paid for all animals, supplies and equipment, except for the A2A knockout mice and littermate controls, which were provided by a grant from Michael Schwarzschild from NIH (K24NS60991) and DoD (W81XWH-11-1-0150), Merce Correa was supported by a grant from Fundacio Bancaixa-UJI (P1.1B2010-43) and Caja Navarra, and Marta Pardo received a travel grant from Fundacio Bancaixa-UJI. NR 33 TC 8 Z9 8 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2013 VL 23 IS 8 BP 972 EP 977 DI 10.1016/j.euroneuro.2012.08.004 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 220QT UT WOS:000324602700027 PM 22947264 ER PT J AU Lagali, N Eden, U Utheim, TP Chen, XJ Riise, R Dellby, A Fagerholm, P AF Lagali, Neil Eden, Ulla Utheim, Tor Paaske Chen, Xiangjun Riise, Ruth Dellby, Anette Fagerholm, Per TI In Vivo Morphology of the Limbal Palisades of Vogt Correlates With Progressive Stem Cell Deficiency in Aniridia-Related Keratopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE limbal palisades of Vogt; corneal stem cells; corneal epithelium; subbasal nerves; aniridia; in vivo confocal microscopy; stem cell deficiency ID CONFOCAL MICROSCOPIC EVALUATION; CORNEAL INNERVATION; EXPRESSION; EPITHELIUM; PHENOTYPE; DENSITY AB PURPOSE. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency. METHODS. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM). RESULTS. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively). CONCLUSIONS. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early-to late-stage degenerative changes in stem cell-deficient patients. C1 [Lagali, Neil; Eden, Ulla; Dellby, Anette; Fagerholm, Per] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden. [Utheim, Tor Paaske] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway. [Utheim, Tor Paaske] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. [Chen, Xiangjun] Synslaser Kirurgi AS, Oslo, Norway. [Riise, Ruth] Innland Hosp, Dept Ophthalmol, Elverum, Norway. RP Lagali, N (reprint author), Linkoping Univ, Fac Hlth Sci, Inst Clin & Expt Med, Dept Ophthalmol, SE-58183 Linkoping, Sweden. EM neil.lagali@liu.se OI Chen, Xiangjun/0000-0003-0331-9028; Lagali, Neil/0000-0003-1079-4361 FU Crown Princess Margareta's Foundation for the Visually Impaired; Carmen and Bertil Regners Foundation for Research in Eye Disease; County Council of Ostergotland; Konung Gustav V and Drottning Viktorias Frimurarestiftelse; The Swedish Research Council; Aniridia Norway FX Supported by Crown Princess Margareta's Foundation for the Visually Impaired, Carmen and Bertil Regners Foundation for Research in Eye Disease, the County Council of Ostergotland, Konung Gustav V and Drottning Viktorias Frimurarestiftelse, The Swedish Research Council, and Aniridia Norway. The authors alone are responsible for the content and writing of the paper. NR 25 TC 22 Z9 23 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2013 VL 54 IS 8 BP 5333 EP 5342 DI 10.1167/iovs.13-11780 PG 10 WC Ophthalmology SC Ophthalmology GA 228EA UT WOS:000325167200024 PM 23860752 ER PT J AU Keller, KE Vranka, JA Haddadin, RI Kang, MH Oh, DJ Rhee, DJ Yang, YF Sun, YY Kelley, MJ Acott, TS AF Keller, Kate E. Vranka, Janice A. Haddadin, Ramez I. Kang, Min-Hyung Oh, Dong-Jin Rhee, Douglas J. Yang, Yong-feng Sun, Ying Ying Kelley, Mary J. Acott, Ted S. TI The Effects of Tenascin C Knockdown on Trabecular Meshwork Outflow Resistance SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE tenascin C; trabecular meshwork; outflow resistance; extracellular matrix ID EXTRACELLULAR-MATRIX TURNOVER; LOWER INTRAOCULAR-PRESSURES; OPEN-ANGLE GLAUCOMA; HEPARIN-II DOMAIN; JUXTACANALICULAR TISSUE; MATRICELLULAR PROTEINS; ANTERIOR SEGMENTS; AQUEOUS OUTFLOW; ORGAN-CULTURE; CELL-FUNCTION AB PURPOSE. Tenascin C (TNC) is a matricellular glycoprotein whose expression in adult tissue is indicative of tissue remodeling. The purpose of the current study was to determine the localization of TNC in trabecular meshwork (TM) tissue and to analyze the effects of TNC on intraocular pressure (IOP). METHODS. Human TM frontal sections were immunostained with anti-TNC and imaged by confocal microscopy. TNC mRNA and protein levels were quantitated in anterior segments perfused at physiological and elevated pressure. Short, hairpin RNA (shRNA) silencing lentivirus targeting full-length TNC (shTNC) was applied to anterior segment perfusion organ cultures. The IOPs and central corneal thickness (CCT) of wild-type, TNC-/-, and tenascin X (TNX-/-) knockout mice were measured. RESULTS. TNC was distributed in the juxtacanalicular (JCT) region of adult human TM, predominantly in the basement membrane underlying the inner wall of Schlemm's canal. Application of shTNC lentivirus to human and porcine anterior segments in perfusion culture did not significantly affect outflow rate. Although TNC was upregulated in response to pressure, there was no difference in outflow rate when shTNC-silenced anterior segments were subjected to elevated pressure. Furthermore, IOPs and CCTs were not significantly different between TNC-/- or TNX-/- and wild-type mice. CONCLUSIONS. TNC does not appear to contribute directly to outflow resistance. However, TNC immunolocalization in the JCT of adult human eyes suggests that certain areas of the TM are being continuously remodeled with or without an IOP increase. C1 [Keller, Kate E.; Vranka, Janice A.; Yang, Yong-feng; Sun, Ying Ying; Kelley, Mary J.; Acott, Ted S.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. [Haddadin, Ramez I.; Kang, Min-Hyung; Oh, Dong-Jin; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Keller, KE (reprint author), Casey Eye Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM gregorka@ohsu.edu FU NIH [EY019643, EY003279, EY008247, EY010572, EY019654]; Fight for Sight Summer Research Program; Northwest Health Foundation; Research to Prevent Blindness, New York, New York FX Supported by NIH Grants EY019643 (KEK), EY003279, EY008247, EY010572 (TSA), EY019654 (DJR); the Fight for Sight Summer Research Program (RIH); the Northwest Health Foundation (MJK); and an unrestricted grant to the Casey Eye Institute from Research to Prevent Blindness, New York, New York. NR 58 TC 8 Z9 8 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2013 VL 54 IS 8 BP 5613 EP 5623 DI 10.1167/iovs.13-11620 PG 11 WC Ophthalmology SC Ophthalmology GA 228EA UT WOS:000325167200060 PM 23882691 ER PT J AU Waldo, SW Armstrong, EJ Kulkarni, A Hoffmayer, KS Hsue, P Ganz, P McCabe, JM AF Waldo, Stephen W. Armstrong, Ehrin J. Kulkarni, Ameya Hoffmayer, Kurt S. Hsue, Priscilla Ganz, Peter McCabe, James M. TI Clinical Characteristics and Reperfusion Times Among Patients With an Isolated Posterior Myocardial Infarction SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE acute coronary syndromes; posterior myocardial infarction; reperfusion time ID ST-SEGMENT ELEVATION; PERCUTANEOUS CORONARY INTERVENTION; ACTIVATE-SF-REGISTRY; TO-BALLOON TIME; PROGNOSTIC-SIGNIFICANCE; DEPRESSION; MANAGEMENT; LEADS; THROMBOLYSIS; PREVALENCE AB Background. An isolated posterior myocardial infarction (PMI) is associated with significant morbidity and mortality. Because physicians often fail to recognize this diagnosis, there may be delays in the timely revascularization of these patients. The present study sought to identify the clinical characteristics and reperfusion times among patients presenting with isolated PMI. Methods. We identified subjects with isolated PMI within a registry of all catheterization laboratory activations for ST-elevation myocardial infarction (STEMI) from 2008 to 2012. Association between PMI and revascularization within 90 minutes was evaluated by logistic regression. Results. Among 318 patients who underwent revascularization for STEMI, a total of 20 (6%) had electrocardiographic evidence of an isolated PMI. Compared to non-PMI STEMI, subjects with PMI were more often female (45% vs 22%; P=.02) and less likely to have chest pain (40% vs 75%; P<.01). The median door-to-activation (25.5 min vs 12 min; P<.01), activation-to-laboratory (36.5 min vs 29 min; P<.01) and door-to-balloon times (107 min vs 72 min; P<.01) were longer among subjects with PMI, with fewer patients achieving reperfusion within 90 minutes (30% vs 71%; P<.01). After multivariable adjustment, individuals with PMI had 82% lower odds (adjusted odds ratio, 0.18; 95% confidence interval, 0.06-0.50) of achieving coronary reperfusion within 90 minutes. Door-to-activation time accounted for 96% of variation in the total revascularization time (R-2=0.96; P<.0001). Conclusions. Door-to-activation time was prolonged for those with PMI, resulting in longer door-to-balloon times and fewer patients revascularized within the recommended time. An isolated PMI should be considered among individuals presenting with symptoms consistent with myocardial infarction. C1 [Waldo, Stephen W.; Hoffmayer, Kurt S.; Hsue, Priscilla; Ganz, Peter] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94134 USA. [Armstrong, Ehrin J.] Univ Calif San Francisco, Dept Med, Div Cardiovasc Med, San Francisco, CA 94134 USA. [Kulkarni, Ameya] Massachusetts Gen Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02114 USA. [McCabe, James M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Waldo, SW (reprint author), Univ Calif San Francisco, Dept Med, Div Cardiol, 505 Parnassus Ave,Box 0124, San Francisco, CA 94134 USA. EM stephen.waldo@ucsf.edu NR 24 TC 4 Z9 4 U1 2 U2 3 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD AUG PY 2013 VL 25 IS 8 BP 371 EP 375 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 224HC UT WOS:000324872700008 PM 23913600 ER PT J AU Arokiaraj, M Guerrero, L Levine, R Palacios, I AF Arokiaraj, Mark Guerrero, Luis Levine, Robert Palacios, Igor TI A Theoretical Cardiac Resynchronization Therapy Method to Augment Ventricular Contraction Using Polymer-Based Actuators and Mitral Regurgitation Reduction With Devices Over Left Ventricular Endocardial Pacing Wire - An In-Vitro Study SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE heart failure; ejection fraction; mitral regurgitation; cardiac resynchronization therapy; polymer actuators; new device ID HEART-FAILURE AB Background. To investigate a potential cardiac resynchronization method using high force density actuators and mitral regurgitation (MR) reduction devices. Methods. An 8-cm long, 0.4-mm thick, and 2-mm wide polymeric actuator strip was attached to the right ventricular (RV) pacemaker lead 4.0 cm from the edge of the leads, and 035 wire and step-up voltages (2-9 V) were given. Deformation of the pacemaker lead with polymer was studied under cine-fluoroscopy in the air and immersing it in 0.9% saline. Cantilever function was assessed by the addition of gold rings. The left ventricular (LV) lead was reinforced with dual polymer and a side branching 035 wire Y-attachment and studied. A novel nitinol-based Gore-Tex device and polymer-based technology was developed and positioned abutting the mitral valves, and was evaluated in sheep heart preparations by cine-fluoroscopy. Results. The mean deformation at 9 V for the LV leads, RV leads, and 035 wires was 3.5 +/- 0.2 mm, 1.1 +/- 0.1 mm, and 1.4 +/- 0.1 mm, respectively, and the stopping weight was 3.8 +/- 0.2 g, 3.2 +/- 0.1 g, and 3.6 +/- 0.3 g, respectively. With dual surfacing of polymer and driven by separate actuation circuits simultaneously, the stopping weight parameters increased to 4.8 +/- 0.2 g, 4.0 +/- 0.2 g, and 4.6 +/- 0.1 g, respectively (>25% each; P<.01 for all). The nitinol-based Gore-Tex device and the polymer device appeared to have reduced MR significantly from grade IV to grade I (>60% by visual quantification). Conclusion. There is potential for a novel theoretical cardiac resynchronization therapy method using polymer-based actuators and devices to control MR. C1 [Arokiaraj, Mark] Pondicherry Inst Med Sci, Pondicherry 605014, India. [Guerrero, Luis; Levine, Robert; Palacios, Igor] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Arokiaraj, M (reprint author), Pondicherry Inst Med Sci, Pondicherry 605014, India. EM christomark@gmail.com FU NHLBI NIH HHS [R01 HL072265] NR 7 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD AUG PY 2013 VL 25 IS 8 BP 415 EP 420 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 224HC UT WOS:000324872700017 PM 23913609 ER PT J AU Lam, DY O'Hare, AM Vig, EK AF Lam, Daniel Y. O'Hare, Ann M. Vig, Elizabeth K. TI Decisions About Dialysis Initiation in the Elderly SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; STARTING DIALYSIS; UNITED-STATES; END; PREVALENCE; LIFE; HEMODIALYSIS; MANAGEMENT; SURVIVAL C1 [Lam, Daniel Y.; O'Hare, Ann M.; Vig, Elizabeth K.] Univ Washington, Seattle, WA 98195 USA. [O'Hare, Ann M.; Vig, Elizabeth K.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lam, DY (reprint author), Univ Washington, Med Ctr, Div Nephrol, 1959 NE Pacific St,Box 356521, Seattle, WA 98195 USA. EM dlam34@u.washington.edu NR 20 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD AUG PY 2013 VL 46 IS 2 BP 298 EP 302 DI 10.1016/j.jpainsymman.2013.05.014 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 213AU UT WOS:000324026100019 PM 23938186 ER PT J AU Muller, AM Sadoghi, P Lucas, R Audige, L Delaney, R Klein, M Valderrabano, V Vavken, P AF Mueller, Andreas M. Sadoghi, Patrick Lucas, Robert Audige, Laurent Delaney, Ruth Klein, Maria Valderrabano, Victor Vavken, Patrick TI Effectiveness of bracing in the treatment of nonosseous restriction of elbow mobility: a systematic review and meta-analysis of 13 studies SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Elbow; stiffness; brace; conservative ID STATIC PROGRESSIVE STRETCH; DISTAL RADIUS FRACTURE; FLEXION CONTRACTURES; SPLINTING APPROACH; WRIST STIFFNESS; SECONDARY; MOTION; TRAUMA; BURNS; KNEE AB Background: Restriction of elbow mobility is a very frequent complaint after trauma or surgery. The objective of this study was to assess and compare the effectiveness of dynamic, static, or staticprogressive bracing in patients with elbow stiffness of traumatic or postoperative origin and without evidence of ossification. For the purpose of this study, effectiveness was measured as the increase in total range of motion, as well as extension and flexion. Materials and methods: We performed a systematic search of the keywords "elbow AND (stiffness OR stiff) AND (brace OR splint OR conservative)" in the online databases PubMed, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Library. We included all clinical studies using dynamic or static bracing in patients with elbow stiffness. Eligible outcomes were changes in total range of motion, flexion, and extension; sustainability of results; and complications. Results: We included 13 eligible studies, providing data on 14 treated groups in 247 patients. The mean age of these patients was 34.5 +/- 10.4 years, and female patients comprised 46% +/- 12%. The mean duration from the incident to the start of brace treatment was 6.9 +/- 5.1 months. The mean improvement in range of motion during the course of treatment was 38.4 degrees +/- 8.9 degrees (95% confidence interval, 39.5 degrees-41.8 degrees). Conclusions: The current evidence strongly supports the use of static-progressive stretching 3 times 30 minutes per day in each direction as a first line of treatment in patients with post-traumatic and postsurgical elbow stiffness. If this treatment fails or if reasons for stiffness other than soft-tissue incompliance are identified, further surgical interventions should be considered. Level of evidence: Level IV, Systematic Review. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Mueller, Andreas M.; Klein, Maria; Valderrabano, Victor; Vavken, Patrick] Univ Basel, Univ Basel Hosp, Dept Orthopaed, Basel, Switzerland. [Mueller, Andreas M.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Sadoghi, Patrick] Med Univ Graz, Dept Orthoped Surg, Graz, Austria. [Lucas, Robert] Univ Calif San Francisco, Dept Orthoped Surg, San Francisco, CA 94143 USA. [Audige, Laurent] Schulthess Clin, Dept Upper Extrem Surg, Zurich, Switzerland. [Delaney, Ruth] Massachusetts Gen Hosp, Harvard Combined Residency Program, Boston, MA 02114 USA. [Vavken, Patrick] Harvard Univ, Childrens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Vavken, Patrick] Harvard Univ, Sch Publ Hlth, Ctr Populat & Dev Studies, Boston, MA 02115 USA. RP Sadoghi, P (reprint author), Auenbruggerpl 5, A-8036 Graz, Austria. EM patricksadoghi@gmx.at OI Sadoghi, Patrick/0000-0003-1767-555X NR 27 TC 4 Z9 4 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD AUG PY 2013 VL 22 IS 8 BP 1146 EP 1152 DI 10.1016/j.jse.2013.04.003 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 221EO UT WOS:000324640700026 PM 23796383 ER PT J AU Ring, D AF Ring, David TI Regarding "Patients that request reconstruction are different" SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 1 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 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD AUG PY 2013 VL 22 IS 8 BP E22 EP E22 DI 10.1016/j.jse.2013.01.013 PG 1 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 221EO UT WOS:000324640700008 PM 23422515 ER PT J AU Strand, JJ Kamdar, MM Carey, EC AF Strand, Jacob J. Kamdar, Mihir M. Carey, Elise C. TI Top 10 Things Palliative Care Clinicians Wished Everyone Knew About Palliative Care SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; CONGESTIVE-HEART-FAILURE; SERIOUSLY ILL PATIENTS; CELL LUNG-CANCER; END; PAIN; ASSOCIATIONS; PREVALENCE; SYMPTOMS AB With a focus on improving quality of life for patients, palliative care is a rapidly growing medical subspecialty focusing on the care of patients with serious illness. Basic symptom management, discussions of prognostic understanding, and eliciting treatment goals are essential pieces in the practice of nearly all physicians. Nonetheless, many complex patients with a serious, life-threatening illness benefit from consultation with palliative care specialists, who are trained and experienced in complex symptom management and challenging communication interactions, including medical decision making and aligning goals of care. This article discusses the changing role of modern palliative care, addresses common misconceptions, and presents an argument for early integration of palliative care in the treatment of patients dealing with serious illness. (C) 2013 Mayo Foundation for Medical Education and Research C1 [Strand, Jacob J.; Carey, Elise C.] Mayo Clin, Palliat Care Sect, Dept Internal Med, Rochester, MN 55905 USA. [Kamdar, Mihir M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Dept Internal Med, Palliat Care Serv, Boston, MA 02114 USA. RP Strand, JJ (reprint author), Mayo Clin, Palliat Care Sect, Dept Internal Med, 200 1st St SW,Gonda 17, Rochester, MN 55905 USA. EM strand.jacob@mayo.edu NR 52 TC 12 Z9 14 U1 2 U2 14 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 AUG PY 2013 VL 88 IS 8 BP 859 EP 865 DI 10.1016/j.mayocp.2013.05.020 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 217CE UT WOS:000324333400016 PM 23910412 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Tadeus Reichstein-Work on Hormones of the Adrenal Glands 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 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 2013 VL 88 IS 8 BP E85 EP E85 DI 10.1016/j.mayocp.2012.01.031 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 217CE UT WOS:000324333400002 PM 23910422 ER PT J AU Yoo, JW Nakagawa, S Kim, S AF Yoo, Ji Won Nakagawa, Shunichi Kim, Sulgi TI Relationships among advance directives, principal diagnoses, and discharge outcomes in critically ill older adults SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Critical care; Health services for the aged; Advance directives; Diagnosis-related groups ID LENGTH-OF-STAY; SEVERE SEPSIS; CARE-UNIT; RESOURCE USE; SURVIVORS; ADMISSION; MEDICARE; MEDICINE; HOSPICE; STATES AB Objective: The purpose of this study was to determine the relationships among advance directive status, principal diagnoses, and the discharge outcomes in community-dwelling, critically ill older adults. Method: Using administrative and clinical data (n = 1673), multinomial logit regressions were used to examine the relationships among advance directive status, principal diagnoses, and discharge outcomes (in-hospital deaths, hospice discharges, and transition to institutions). Results: In the overall sample, the adjusted probability of in-hospital deaths with advance directives (12%) was lower than that without advance directives (17%; odds ratio [OR] 0.56; p = 0.007) and the adjusted probability of hospice discharges with advance directives (11%) was higher than that without advance directives (7%; OR = 1.96; p = 0.03). Subgroup analysis showed that the magnitude of the abovementioned changes was aggregated when their principal diagnoses were a group of diseases with more difficult prognostication (circulatory and respiratory diseases) and more potential for reversibility (infectious diseases). By contrast, the magnitude of the abovementioned findings was diminished with other principal diagnoses. On the other hand, the presence of advance directives did not make a contribution to transition from communities to institutions. Significance of results: Significantly fewer in-hospital deaths in addition to higher hospice discharges were observed with any advance directives in community-dwelling, critically ill older adults. The magnitude of these findings was aggregated when their principal diagnoses were a group of diseases with more difficult prognostication (circulatory and respiratory diseases) and more potential for reversibility (infectious diseases). By contrast, the magnitude of these findings was diminished with other principal diagnoses. C1 [Yoo, Ji Won] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Nakagawa, Shunichi] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Nakagawa, Shunichi] James J Peters Vet Affairs Med Ctr, Educ & Clin Ctr, Bronx, NY USA. [Kim, Sulgi] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Yoo, Ji Won] Korea Univ, Dept Internal Med, Seoul, South Korea. RP Yoo, JW (reprint author), Univ Michigan, Sch Med, 300 North Ingalls Bldg,Room 932, Ann Arbor, MI 48109 USA. EM yoojiw@trinity-health.org NR 37 TC 1 Z9 1 U1 3 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD AUG PY 2013 VL 11 IS 4 BP 315 EP 322 DI 10.1017/S1478951512000259 PG 8 WC Health Policy & Services SC Health Care Sciences & Services GA 219XL UT WOS:000324544900005 PM 22892195 ER PT J AU Stiens, SA Fawber, HL Yuhas, SA AF Stiens, Steven A. Fawber, Heidi L. Yuhas, Steven A. TI The Person with a Spinal Cord Injury An Evolving Prototype for Life Care Planning SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Spinal cord injury; Life care plan; Problem list; Patient-centered care; Cost of care; Outcome; Prevention ID QUALITY-OF-LIFE; NEUROGENIC BOWEL; MEDICINE; ADJUSTMENT; EMPLOYMENT; PEOPLE AB The sequela of spinal cord injury (SCI) can provide a prototype for life care planning because the segmental design of the vertebrate body allows assessments to be quantitative, repeatable, and predictive of the injured person's impairments, self-care capabilities, and required assistance. Life care planning for patients with SCI uses a standard method that is comparable between planner, yet individualizes assessment and seeks resources that meet unique patient-centered needs in their communities of choice. Clinical care and rehabilitation needs organized with an SCI problem list promotes collaboration by the interdisciplinary team, caregivers, and family in efficient achievement of patient-centered goals and completion of daily care plans. C1 [Stiens, Steven A.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Stiens, Steven A.] Univ Washington, Seattle, WA 98195 USA. [Stiens, Steven A.] Univ Hosp, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Fawber, Heidi L.; Yuhas, Steven A.] Int Assoc Rehabil Profess, Int Acad Life Care Planners Sect, Glenview, IL 60025 USA. [Yuhas, Steven A.] Direct Grp Inc, Mt Pleasant, SC 29464 USA. RP Stiens, SA (reprint author), Univ Hosp, VA Puget Sound Hlth Care Syst, POB 356490,Hlth Sci Bldg,1959 North East Pacific, Seattle, WA 98195 USA. EM Steven.Stiens@va.gov FU Lou and Virginia Muhlhofer, Cincinnati, OH, USA FX Lou and Virginia Muhlhofer, Cincinnati, OH, USA. NR 51 TC 1 Z9 1 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD AUG PY 2013 VL 24 IS 3 BP 419 EP + DI 10.1016/j.pmr.2013.03.006 PG 27 WC Rehabilitation SC Rehabilitation GA 214QG UT WOS:000324149800004 PM 23910484 ER PT J AU Harshman, LC Taplin, ME AF Harshman, Lauren C. Taplin, Mary-Ellen TI Abiraterone Acetate: Targeting Persistent Androgen Dependence in Castration-Resistant Prostate Cancer SO ADVANCES IN THERAPY LA English DT Review DE Abiraterone; Androgen dependence; Castration-resistant prostate cancer; CYP17 inhibitor; Oncology; Prostate cancer; Survival ID MITOXANTRONE PLUS PREDNISONE; I CLINICAL-TRIAL; LEUKEMIA GROUP-B; PHASE-II; INCREASED SURVIVAL; HORMONAL-THERAPY; RANDOMIZED-TRIAL; END-POINTS; C-MET; RECEPTOR AB Abiraterone acetate is the first second-line hormonal agent proven to improve survival in metastatic castration-resistant prostate cancer. It selectively inhibits cytochrome P450 17 (CYP17) alpha-hydroxylase and cytochrome(17,20) (C-17,C-20)-lyase, which are enzymes critical for androgen synthesis. Abiraterone acetate was initially approved in the United States in 2011 after demonstrating a 4-month survival benefit in docetaxel-refractory metastatic prostate cancer. The FDA recently expanded its indication for use in the pre-chemotherapy setting after it elicited significant delays in disease progression and a strong trend for increased overall survival in phase III studies. Ongoing investigations of abiraterone are evaluating its efficacy in earlier disease states, exploring its synergy in combination with other therapeutic agents, and assessing the necessity for administration of concurrent steroids and gonadal suppression. The identification and development of predictive biomarkers will optimize the incorporation of abiraterone into the management of advanced prostate cancer. C1 [Harshman, Lauren C.; Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Harshman, LC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA. EM laurenc_harshman@dfci.harvard.edu FU Fairweather and Uribe Prostate Cancer Research Funds FX This work was supported in part by the Fairweather and Uribe Prostate Cancer Research Funds. Drs. Harshman and Taplin contributed equally to the original design, writing, and revision of this review article. No editorial or medical writing assistance was utilized. Prior to peer review, Janssen was offered the opportunity to review this paper for scientific accuracy. Dr. Harshman is the guarantor for this article, and takes responsibility for the integrity of the work as a whole. NR 72 TC 7 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0741-238X J9 ADV THER JI Adv. Ther. PD AUG PY 2013 VL 30 IS 8 BP 727 EP 747 DI 10.1007/s12325-013-0050-3 PG 21 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 216ZH UT WOS:000324325400002 PM 23979793 ER PT J AU Pannucci, NL Li, D Sahay, S Thomas, EK Chen, R Tala, I Hu, T Ciccarelli, BT Megjugorac, NJ Adams, HC Rodriguez, PL Fitzpatrick, ER Lagunoff, D Williams, DA Whitehead, IP AF Pannucci, N. L. Li, D. Sahay, S. Thomas, E. K. Chen, R. Tala, I. Hu, T. Ciccarelli, B. T. Megjugorac, N. J. Adams, H. C., III Rodriguez, P. L. Fitzpatrick, E. R. Lagunoff, D. Williams, D. A. Whitehead, I. P. TI Loss of the xeroderma pigmentosum group B protein binding site impairs p210 BCR/ABL1 leukemogenic activity SO BLOOD CANCER JOURNAL LA English DT Article DE chronic myelogenous leukemia; p210 BCR/ABL1; XPB; NER; DNA repair ID CHRONIC MYELOGENOUS LEUKEMIA; NUCLEOTIDE EXCISION-REPAIR; BASIC TRANSCRIPTION FACTOR; C-MYC EXPRESSION; BCR-ABL; DNA-DAMAGE; MYELOPROLIFERATIVE DISEASE; INDUCED APOPTOSIS; BTF2 TFIIH; RESISTANCE AB Previous studies have demonstrated that p210 BCR/ABL1 interacts directly with the xeroderma pigmentosum group B (XPB) protein, and that XPB is phosphorylated on tyrosine in cells that express p210 BCR/ABL1. In the current study, we have constructed a p210 BCR/ABL1 mutant that can no longer bind to XPB. The mutant has normal kinase activity and interacts with GRB2, but can no longer phosphorylate XPB. Loss of XPB binding is associated with reduced expression of c-MYC and reduced transforming potential in ex-vivo clonogenicity assays, but does not affect nucleotide excision repair in lymphoid or myeloid cells. When examined in a bone marrow transplantation (BMT) model for chronic myelogenous leukemia, mice that express the mutant exhibit attenuated myeloproliferation and lymphoproliferation when compared with mice that express unmodified p210 BCR/ABL1. Thus, the mutant-transplanted mice show predominantly neutrophilic expansion and altered progenitor expansion, and have significantly extended lifespans. This was confirmed in a BMT model for B-cell acute lymphoblastic leukemia, wherein the majority of the mutant-transplanted mice remain disease free. These results suggest that the interaction between p210 BCR/ABL1 and XPB can contribute to disease progression by influencing the lineage commitment of lymphoid and myeloid progenitors. C1 [Pannucci, N. L.; Li, D.; Sahay, S.; Chen, R.; Tala, I.; Hu, T.; Ciccarelli, B. T.; Megjugorac, N. J.; Adams, H. C., III; Rodriguez, P. L.; Fitzpatrick, E. R.; Lagunoff, D.; Whitehead, I. P.] Univ Med & Dent New Jersey, New Jersey Med Sch, Univ Hosp Canc Ctr, Newark, NJ 07101 USA. [Thomas, E. K.] Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Res Fdn, Div Expt Hematol, Cincinnati, OH 45229 USA. [Williams, D. A.] Harvard Univ, Sch Med, Hematol Oncol Div, Childrens Hosp Boston, 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, New Jersey Med Sch, Univ Hosp Canc Ctr, Canc Ctr Level H, 205 South Orange Ave, Newark, NJ 07101 USA. EM whiteip@umdnj.edu RI Hu, Tinghui/F-3213-2015 FU Public Health Service [CA097066, DK62757]; New Jersey Commission for Cancer Research FX This work was supported by the Public Health Service grants CA097066 (IPW) and DK62757 (DAW). NLP, PLR and ERF is a recipient of a fellowship from the New Jersey Commission for Cancer Research. NLP are recipients of fellowships from NJCCR. NR 42 TC 2 Z9 2 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD AUG PY 2013 VL 3 AR UNSP e135 DI 10.1038/bcj.2013.36 PG 10 WC Oncology SC Oncology GA 214XK UT WOS:000324171500007 PM 23955590 ER PT J AU Chen, BB Glasser, JR Coon, TA Mallampalli, RK AF Chen, B. B. Glasser, J. R. Coon, T. A. Mallampalli, R. K. TI Skp-cullin-F box E3 ligase component FBXL2 ubiquitinates Aurora B to inhibit tumorigenesis SO CELL DEATH & DISEASE LA English DT Article DE ubiquitin; tumor; proteolysis; drug; small molecule ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; SPINDLE ASSEMBLY CHECKPOINT; HISTONE H3 PHOSPHORYLATION; KINASE INHIBITOR; KINETOCHORE ORIENTATION; CHROMOSOME CONDENSATION; MITOTIC PROGRESSION; REGULATORY ENZYME; HUMAN-CELLS; PROTEIN AB Aurora B kinase is an integral regulator of cytokinesis, as it stabilizes the intercellular canal within the midbody to ensure proper chromosomal segregation during cell division. Here we identified that the ubiquitin E3 ligase complex SCFFBXL2 mediates Aurora B ubiquitination and degradation within the midbody, which is sufficient to induce mitotic arrest and apoptosis. Three molecular acceptor sites (K-102, K-103 and K-207) within Aurora B protein were identified as important sites for its ubiquitination. A triple Lys mutant of Aurora B (K-102/103/207R) exhibited optimal resistance to SCFFBXL2-directed polyubiquitination, and overexpression of this variant resulted in a significant delay in anaphase onset, resulting in apoptosis. A unique small molecule F-box/LRR-repeat protein 2 (FBXL2) activator, BC-1258, stabilized and increased levels of FBXL2 protein that promoted Aurora B degradation, resulting in tetraploidy, mitotic arrest and apoptosis of tumorigenic cells, and profoundly inhibiting tumor formation in athymic nude mice. These findings uncover a new proteolytic mechanism targeting a key regulator of cell replication that may serve as a basis for chemotherapeutic intervention in neoplasia. C1 [Chen, B. B.; Glasser, J. R.; Coon, T. A.; Mallampalli, R. K.] Univ Pittsburgh, Dept Med Pulm Allergy & Crit Care Med, UPMC Montefiore, Pittsburgh, PA 15213 USA. [Chen, B. B.] Univ Pittsburgh, Dept Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, R. K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, R. K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Chen, BB (reprint author), Univ Pittsburgh, Dept Med Pulm Allergy & Crit Care Med, UPMC Montefiore, 3459 5th Ave,NW 628, Pittsburgh, PA 15213 USA. EM chenb@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health [HL116472, HL096376, HL097376, HL098174] FX We thank DW Gerlich for providing pH2B-mCherry-IRES-puro2 and pMyrPalm-mEGFP plasmids. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and 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 HL116472 (to BBC), HL096376, HL097376 and HL098174 (to RKM). NR 49 TC 14 Z9 14 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD AUG PY 2013 VL 4 AR e759 DI 10.1038/cddis.2013.271 PG 10 WC Cell Biology SC Cell Biology GA 214PK UT WOS:000324146000016 PM 23928698 ER PT J AU Clark, KB Eisenstein, EM AF Clark, Kevin B. Eisenstein, E. M. TI Targeting Host Store-Operated Ca2+ Release to Attenuate Viral Infections SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE diarrhea; intracellular Ca2+ signaling; IP3 pathway and receptors; protein-protein allostery; T cells; viral replication; virus-associated dementia; virus-induced cytotoxicity ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; EPSTEIN-BARR-VIRUS; ENDOPLASMIC-RETICULUM MEMBRANE; CEREBELLAR PURKINJE-CELLS; POLYAMINE-SENSITIVE-SITE; LONG-TERM POTENTIATION; NA+/H+ EXCHANGER NHE3; D-ASPARTATE RECEPTOR; LIGAND-BINDING SITE; TRISPHOSPHATE RECEPTOR AB Viruses coopt host intracellular Ca2+ signaling pathways to optimize timing and effectiveness of infection stages against barriers to invasion, pathogenesis, replication, and release. Virus-induced changes in free cytosolic Ca2+ levels facilitate virus adsorption, uncoating, catalysis, toxin production, structural assembly and stabilization, trafficking, and fusion and budding. Ca2+-associated alterations in virus status also selectively precipitate host cytopathologies through, among other events, retardation or induction of apoptosis, elevation of metabolic stress and reactive oxygen species production, and promotion of proinflammatory cytokine and chemokine synthesis and release. Viral particles and proteins tune spatiotemporal dynamics of host free cytosolic Ca2+ concentrations by modulating Ca2+ entry from the extracellular environment, upstream first or second messengers, ion-and ATP-dependent Ca2+ pumps that sequester or extrude free cytosolic Ca2+, store-operated Ca2+ mobilization and leakage, and viral capsid/envelope and downstream host Ca2+ binding proteins and sensors. Each of these major viral mechanisms, briefly reviewed in this article, presents a suitable drug target capable of mitigating the severity and incidence of viral infections. Given its pivotal role in cellular response regulation, bioenergetics, posttranslational protein and lipid modification and transport, homeostasis, cell motility and morphogenesis, and T lymphocyte proliferation, targeting virally stimulated inositol 1,4,5-trisphoshate (IP3)-mediated store-operated Ca2+ release especially offers unique, predictable benefits for augmenting immunoprotection in vertebrate clinical populations. We appraise possibilities of modulating this system with experimental proteins that gate activation kinetics of endoplasmic-reticulum-localized Ca2+-conducting IP3 receptors via allosteric protein-protein interactions. Such compounds are expected to be valuable in treating primary disease symptoms and sequelae, including virus-associated dementia. C1 [Eisenstein, E. M.] Vet Affairs Greater Los Angeles Hlth Care Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. RP Clark, KB (reprint author), 4229 SE Harney St, Portland, OR 97206 USA. EM kbclarkphd@yahoo.com NR 220 TC 3 Z9 3 U1 4 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD AUG PY 2013 VL 13 IS 16 BP 1916 EP 1932 PG 17 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 214WH UT WOS:000324167500003 PM 23895094 ER PT J AU Klassert, TB Hanisch, A Brauer, J Mansour, MK Vyas, JM Tam, JM Slevogt, H AF Klassert, T. B. Hanisch, A. Braeuer, J. Mansour, M. K. Vyas, J. M. Tam, J. M. Slevogt, H. TI Modulatory role of nuclear receptors on the C. albicans-induced immune response in human monocytes SO INFECTION LA English DT Meeting Abstract C1 [Klassert, T. B.; Hanisch, A.; Braeuer, J.; Slevogt, H.] Jena Univ Hosp, Sept Res Ctr, Jena, Germany. [Klassert, T. B.; Hanisch, A.; Braeuer, J.; Slevogt, H.] Univ Jena, Jena, Germany. [Hanisch, A.] Jena Univ Hosp, Ctr Sepsis Control & Care, Jena, Germany. [Mansour, M. K.; Vyas, J. M.; Tam, J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Infect Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD AUG PY 2013 VL 41 SU 1 MA 132 BP S29 EP S29 PG 1 WC Infectious Diseases SC Infectious Diseases GA 216KG UT WOS:000324281600057 ER PT J AU Assoumou, SA Panther, LA Feng, Y Gelman, RS Fugelso, DK Mayer, KH AF Assoumou, S. A. Panther, L. A. Feng, Y. Gelman, R. S. Fugelso, D. K. Mayer, K. H. TI Treatment of high-grade anal dysplasia in high-risk patients: outcome at an urban community health centre (vol 24, pg 134, 2013) SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Correction C1 [Assoumou, S. A.] Boston Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA. [Panther, L. A.; Mayer, K. H.] Fenway Inst, Boston, MA USA. [Panther, L. A.; Mayer, K. H.] Beth Israel Deaconess Med Ctr, Dept Med, Div Infect Dis, Boston, MA 02215 USA. [Feng, Y.; Gelman, R. S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gelman, R. S.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fugelso, D. K.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. RP Assoumou, SA (reprint author), Boston Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD AUG PY 2013 VL 24 IS 8 BP 683 EP 683 DI 10.1177/0956462413501415 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 214EP UT WOS:000324114200015 ER PT J AU Fattori, R Montgomery, D Lovato, L Kische, S Di Eusanio, M Ince, H Eagle, KA Isselbacher, EM Nienaber, CA AF Fattori, Rossella Montgomery, Daniel Lovato, Luigi Kische, Stephan Di Eusanio, Marco Ince, Hueseyin Eagle, Kim A. Isselbacher, Eric M. Nienaber, Christoph A. TI Survival After Endovascular Therapy in Patients With Type B Aortic Dissection A Report From the International Registry of Acute Aortic Dissection (IRAD) SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE aorta; stent graft; survival ID STENT-GRAFT PLACEMENT; LONG-TERM SURVIVAL; EXPERIENCE; REPAIR; INSIGHTS; DETERMINANTS; ANEURYSMS; LESSONS; STILL AB Objectives This study sought to evaluate long-term survival in type B aortic dissection patients treated with thoracic endovascular aortic repair (TEVAR) therapy. Background Historical data have supported medical therapy in type B acute aortic dissection (TBAAD) patients. Recent advances in TEVAR appear to improve in-hospital mortality. Methods We examined 1,129 consecutive patients with TBAAD enrolled in IRAD (International Registry of Acute Aortic Dissection) between 1995 and 2012 who received medical (n = 853, 75.6%) or TEVAR (n = 276, 24.4%) therapy. Results Clinical history was similar between groups. TEVAR patients were more likely to present with a pulse deficit (28.3% vs. 13.4%, p < 0.001) and lower extremity ischemia (16.8% vs. 3.6%, p < 0.001), and to characterize their pain as the "worst pain ever" (27.5% vs. 15.7%, p < 0.001). TEVAR patients were also most likely to present with complicated acute aortic dissection, defined as shock, periaortic hematoma, signs of malperfusion, stroke, spinal cord ischemia, mesenteric ischemia, and/or renal failure (61.7% vs. 37.2%). In-hospital mortality was similar in patients managed with endovascular repair (10.9 % vs. 8.7%, p = 0.273) compared with medically managed patients. One-year mortality was also similar in both groups (8.1% endovascular vs. 9.8% medical, p = 0.604). Among adverse events during follow-up, aortic growth/new aneurysm was most common, occurring in 73.3% of patients with medical therapy and in 62.7% of patients after TEVAR, based on 5-year Kaplan-Meier estimates. Kaplan-Meier survival estimates showed that patients undergoing TEVAR had a lower death rate (15.5% vs. 29.0%, p = 0.018) at 5 years. Conclusions Results from IRAD show that TEVAR is associated with lower mortality over a 5-year period than medical therapy for TBAAD. Further randomized trials with long-term follow-up are needed. (C) 2013 by the American College of Cardiology Foundation C1 [Fattori, Rossella] San Salvatore Hosp, Intervent Cardiol Unit, I-61121 Pesaro, Italy. [Montgomery, Daniel; Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Lovato, Luigi; Di Eusanio, Marco] Univ Hosp S Orsola, Cardiothoracovasc Dept, Bologna, Italy. [Kische, Stephan; Ince, Hueseyin; Nienaber, Christoph A.] Univ Rostock, Ctr Heart, D-18055 Rostock, Germany. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. RP Fattori, R (reprint author), San Salvatore Hosp, Int Cardiol Unit, Piazzale Cinelli 4, I-61121 Pesaro, Italy. EM rossella.fattori@unibo.it FU W.L. Gore & Associates, Inc.; Varbedian Aortic Research Fund; Hewlett Foundation; Mardigian Foundation; UM Faculty Group Practice; Terumo; Gore FX IRAD was funded by W.L. Gore & Associates, Inc., Varbedian Aortic Research Fund, Hewlett Foundation, Mardigian Foundation, UM Faculty Group Practice, and Terumo. Dr. Eagle has received research funding from Gore; and is a consultant for the National Heart, Lung, and Blood Institute, National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 29 TC 67 Z9 71 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD AUG PY 2013 VL 6 IS 8 BP 876 EP 882 DI 10.1016/j.jcin.2013.05.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 216TW UT WOS:000324308400014 PM 23968705 ER PT J AU Hoge, EA Bui, E Marques, L Metcalf, CA Morris, LK Robinaugh, DJ Worthington, JJ Pollack, MH Simon, NM AF Hoge, Elizabeth A. Bui, Eric Marques, Luana Metcalf, Christina A. Morris, Laura K. Robinaugh, Donald J. Worthington, John J. Pollack, Mark H. Simon, Naomi M. TI Randomized Controlled Trial of Mindfulness Meditation for Generalized Anxiety Disorder: Effects on Anxiety and Stress Reactivity SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; OLDER-ADULTS; PSYCHOMETRIC PROPERTIES; CLINICAL-TRIALS; ATTENUATION; RELAXATION; INSTRUMENT; PREDICTORS; SYMPTOMS; VALIDITY AB Objective: Mindfulness meditation has met increasing interest as a therapeutic strategy for anxiety disorders, but prior studies have been limited by methodological concerns, including a lack of an active comparison group. This is the first randomized, controlled trial comparing the manualized Mindfulness-Based Stress Reduction (MBSR) program with an active control for generalized anxiety disorder (GAD), a disorder characterized by chronic worry and physiologic hyperarousal symptoms. Method: Ninety-three individuals with DSM-IV-diagnosed GAD were randomly assigned to an 8-week group intervention with MBSR or to an attention control, Stress Management Education (SME), between 2009 and 2011. Anxiety symptoms were measured with the Hamilton Anxiety Rating Scale (HAMA; primary outcome measure), the Clinical Global Impressions-Severity of Illness and -Improvement scales (CGI-S and CGI-I), and the Beck Anxiety Inventory (BAI). Stress reactivity was assessed by comparing anxiety and distress during pretreatment and posttreatment administration of the Trier Social Stress Test (TSST). Results: A modified intent-to-treat analysis including participants who completed at least 1 session of MBSR (n=48) or SME (n=41) showed that both interventions led to significant (P < .0001) reductions in HAMA scores at endpoint, but did not significantly differ. MBSR, however, was associated with a significantly greater reduction in anxiety as measured by the CGI-S, the CGI-I, and the BAI (all P values < .05). MBSR was also associated with greater reductions than SME in anxiety and distress ratings in response to the TSST stress challenge (P < .05) and a greater increase in positive self-statements (P=.004). Conclusions: These results suggest that MBSR may have a beneficial effect on anxiety symptoms in GAD and may also improve stress reactivity and coping as measured in a laboratory stress challenge. Trial Registration: ClinicalTrials.gov identifier: NCT01033851 (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Hoge, Elizabeth A.; Bui, Eric; Marques, Luana; Metcalf, Christina A.; Morris, Laura K.; Robinaugh, Donald J.; Worthington, John J.; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pollack, Mark H.] Rush Univ, Dept Psychiat, Med Ctr, Chicago, IL 60612 USA. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ehoge@partners.org RI Hoge, Elizabeth/H-5879-2012; Bui, Eric/J-8347-2015 OI Hoge, Elizabeth/0000-0002-5513-2292; Bui, Eric/0000-0002-1413-6473 FU National Center on Complementary and Alternative Medicine, National Institutes of Health [K23AT4432]; Highland Street Foundation FX This study was primarily supported by grant K23AT4432 from the National Center on Complementary and Alternative Medicine, National Institutes of Health (Dr Hoge, principal investigator). The Highland Street Foundation provided additional support, including to Drs Bui, Marques, Pollack, and Simon and Ms Metcalf. NR 45 TC 38 Z9 38 U1 9 U2 130 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2013 VL 74 IS 8 BP 786 EP 792 DI 10.4088/JCP.12m08083 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 212NI UT WOS:000323989700001 PM 23541163 ER PT J AU Rosenberg, PB Lanctot, KL Drye, LT Herrmann, N Scherer, RW Bachman, DL Mintzer, JE AF Rosenberg, Paul B. Lanctot, Krista L. Drye, Lea T. Herrmann, Nathan Scherer, Roberta W. Bachman, David L. Mintzer, Jacobo E. CA ADMET Investigators TI Safety and Efficacy of Methylphenidate for Apathy in Alzheimer's Disease: A Randomized, Placebo-Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEXTROAMPHETAMINE CHALLENGE; NEUROPSYCHIATRIC SYMPTOMS; DEMENTIA; DEPRESSION; RELIABILITY; SERTRALINE; DOPAMINE; VALIDITY; DESIGN; CARE AB Objective: In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Apathy in Dementia Methylphenidate Trial (ADMET). Method: Six-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer's disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety. Results: 60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n=37) were female. After 6 weeks' treatment, mean (SD) change in AES score was -1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss >2% in the methylphenidate-treated group. Conclusions: Methylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease. Trial Registration: ClinicalTrials.gov identifier: NCT01117181 (C) Copyright 2013 Physicians Postgraduate Press, Inc. C1 [Rosenberg, Paul B.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Drye, Lea T.; Scherer, Roberta W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lanctot, Krista L.; Herrmann, Nathan] Univ Toronto, Sunnybrook Res Inst, Dept Psychiat, Toronto, ON M5S 1A1, Canada. [Lanctot, Krista L.; Herrmann, Nathan] Univ Toronto, Sunnybrook Res Inst, Brain Sci Res Program, Toronto, ON M5S 1A1, Canada. [Lanctot, Krista L.; Herrmann, Nathan] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada. [Lanctot, Krista L.; Herrmann, Nathan] Univ Toronto, Dept Pharmacol Toxicol, Toronto, ON M5S 1A1, Canada. [Bachman, David L.; Mintzer, Jacobo E.] Med Univ S Carolina, Dept Neurosci, Alzheimers Res Program, Charleston, SC 29425 USA. [Bachman, David L.; Mintzer, Jacobo E.] Med Univ S Carolina, Dept Neurosci, Alzheimers Clin Program, Charleston, SC 29425 USA. [Bachman, David L.; Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mintzer, JE (reprint author), Alzheimers Res Program, 5900 Core Rd,Ste 203, Charleston, SC 29406 USA. EM mintzerj@musc.edu OI Drye, Lea/0000-0002-2964-1878 FU National Institute on Aging [R01 AG033032-01, 1 K08 AG029157-01A1] FX National Institute on Aging (R01 AG033032-01 and 1 K08 AG029157-01A1). NR 27 TC 31 Z9 35 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2013 VL 74 IS 8 BP 810 EP 816 DI 10.4088/JCP.12m08099 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 212NI UT WOS:000323989700004 PM 24021498 ER PT J AU Teo, AR Du, YB Escobar, JI AF Teo, Alan R. Du, Ye B. Escobar, Javier I. TI How can we better manage difficult patient encounters? SO JOURNAL OF FAMILY PRACTICE LA English DT Editorial Material ID CARE; OUTCOMES; HEALTH C1 [Teo, Alan R.] Portland VA Med Ctr, Portland, OR USA. [Teo, Alan R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Du, Ye B.] Columbia Univ, Dept Psychiat, New York, NY USA. [Escobar, Javier I.] Rutgers Robert Wood Johnson Med Sch, Dept Psychiat & Family Med, New Brunswick, NJ USA. RP Teo, AR (reprint author), 3710 SW US Vet Hosp Rd,R&D66, Portland, OR 97239 USA. EM alan.teo@va.gov NR 19 TC 5 Z9 5 U1 0 U2 3 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD AUG PY 2013 VL 62 IS 8 BP 414 EP 421 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 218WW UT WOS:000324464300005 PM 24143334 ER PT J AU Silverberg, ND Lange, RT Millis, SR Rose, A Hopp, G Leach, S Iverson, GL AF Silverberg, Noah D. Lange, Rael T. Millis, Scott R. Rose, Alice Hopp, Grace Leach, Suzanne Iverson, Grant L. TI Post-Concussion Symptom Reporting after Multiple Mild Traumatic Brain Injuries SO JOURNAL OF NEUROTRAUMA LA English DT Article DE concussion; cumulative effects; head trauma; mild traumatic brain injury; post-concussion syndrome ID SPORT-RELATED CONCUSSION; POSTCONCUSSION-LIKE SYMPTOMS; COLLEGIATE FOOTBALL PLAYERS; HEAD-INJURY; NEUROCOGNITIVE PERFORMANCE; TEMPORAL WINDOW; PROFESSIONAL FOOTBALL; RECURRENT CONCUSSION; HISTORY; VULNERABILITY AB The relationship between previous mild traumatic brain injury/ injuries (MTBI) and recovery from a subsequent MTBI may be complex. The present study investigated three factors hypothesized to influence this relation: (1) the number of prior MTBIs, (2) the interval between MTBIs, and (3) the certainty level of previous MTBIs. The study design was retrospective cross-sectional. Participants (N = 105) were evaluated at a concussion clinic on average 1 month after sustaining an MTBI, defined by World Health Organization diagnostic criteria. Approximately half the sample had at least one previous MTBI. Subgroups with 0, 1, or 2 + previous MTBIs did not differ in levels of current post-concussion symptom reporting on the British Columbia Post-Concussion Symptom Inventory. Time since the most recent previous MTBI was significantly associated with current post-concussion symptom reporting. This relation was best characterized as logarithmic; i.e., the impact of previous MTBI(s) lessens exponentially as time elapses to a subsequent MTBI. Defining previous MTBIs with a higher certainty level (i.e., probable versus possible) was not consistently associated with greater post-concussion symptom reporting. In conclusion, participants with multiple MTBIs did not report more post-concussion symptoms than those with no history of MTBI. Previous MTBI(s), however, were associated with increased symptom reporting from a subsequent MTBI to the extent they occurred closer in time. Having one or two previous remote MTBIs was not associated with worse outcome from subsequent MTBI in this sample. C1 [Silverberg, Noah D.] Univ British Columbia, Div Phys Med & Rehabil, Dept Med, GF Strong Rehab Ctr, Vancouver, BC V5Z 2G9, Canada. [Lange, Rael T.] Walter Reed Natl Mil Med Ctr, Def & Vet Brain Injury Ctr, North Bethesda, MD USA. [Lange, Rael T.] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 2G9, Canada. [Millis, Scott R.] Wayne State Univ, Sch Med, Dept Phys Med & Rehabil, Detroit, MI USA. [Rose, Alice] GF Strong Rehab Ctr, Vancouver, BC, Canada. [Hopp, Grace] Independent Practice, Port Coquitlam, BC, Canada. [Leach, Suzanne] Simon Fraser Univ, Ctr Students Disabil, Burnaby, BC V5A 1S6, Canada. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Silverberg, ND (reprint author), Univ British Columbia, Div Phys Med & Rehabil, Dept Med, GF Strong Rehab Ctr, 4255 Laurel St, Vancouver, BC V5Z 2G9, Canada. EM noah.silverberg@vch.ca NR 57 TC 10 Z9 10 U1 2 U2 26 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2013 VL 30 IS 16 BP 1398 EP 1404 DI 10.1089/neu.2012.2827 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 199JB UT WOS:000322989500003 PM 23458451 ER PT J AU Edwards, SD Lipson, JA Ikeda, DM Lee, JM AF Edwards, Sonya D. Lipson, Jafi A. Ikeda, Debra M. Lee, Janie M. TI Updates and Revisions to the BI-RADS Magnetic Resonance Imaging Lexicon SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Breast; MRI; BI-RADS; Lexicon ID BREAST IMPLANT RUPTURE; BACKGROUND PARENCHYMAL ENHANCEMENT; CONTRAST-MEDIUM ENHANCEMENT; COMPUTER-AIDED EVALUATION; POSITIVE PREDICTIVE-VALUE; DIFFERENTIAL-DIAGNOSIS; FOLLOW-UP; NONMASSLIKE ENHANCEMENT; ENHANCING LESIONS; SIGNAL INTENSITY AB This article summarizes the updates and revisions to the second edition of the BI-RADS MRI lexicon. A new feature in the lexicon is background parenchymal enhancement and its descriptors. Another major focus is on revised terminology for masses and non-mass enhancement. A section on breast implants and associated lexicon terms has also been added. Because diagnostic breast imaging increasingly includes multimodality evaluation, the new edition of the lexicon also contains revised recommendations for combined reporting with mammography and ultrasound if these modalities are included as comparison, and clarification on the use of final assessment categories in MR imaging. C1 [Edwards, Sonya D.; Lipson, Jafi A.; Ikeda, Debra M.] Stanford Univ, Med Ctr, Dept Radiol, Stanford Comprehens Canc Ctr, Stanford, CA 94305 USA. [Lee, Janie M.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. RP Lee, JM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM janie@mgh-ita.org NR 58 TC 13 Z9 16 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD AUG PY 2013 VL 21 IS 3 BP 483 EP + DI 10.1016/j.mric.2013.02.005 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 214QN UT WOS:000324150500004 PM 23928239 ER PT J AU Scahill, L Woods, DW Himle, MB Peterson, AL Wilhelm, S Piacentini, JC McNaught, K Walkup, JT Mink, JW AF Scahill, Lawrence Woods, Douglas W. Himle, Michael B. Peterson, Alan L. Wilhelm, Sabine Piacentini, John C. McNaught, Kevin Walkup, John T. Mink, Jonathan W. TI Current controversies on the role of behavior therapy in Tourette syndrome SO MOVEMENT DISORDERS LA English DT Article DE Tourette syndrome; tics; habit reversal therapy; evidence-based treatment ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; HABIT-REVERSAL; TIC DISORDERS; CHILDREN; GUIDELINES; EFFICACY; BRAIN AB Comprehensive behavioral intervention for tics (CBIT) is a safe and effective treatment for managing the tics of Tourette syndrome (TS). In contrast to most current medications used for the treatment of tics, the efficacy of CBIT has been demonstrated in 2 relatively large, multisite trials. It also shows durability of benefit over time. Similar to psychopharmacological intervention, skilled practitioners are required to implement the intervention. Despite concerns about the effort required to participate in CBIT, patients with TS and parents of children with TS appear willing to meet the requirements of the CBIT program. Efforts are under way to increase the number of trained CBIT providers in the United States. Based on available evidence, recent published guidelines suggest that CBIT can be considered a first-line treatment for persons with tic disorders. (c) 2013 Movement Disorder Society C1 [Scahill, Lawrence] Emory Univ, Sch Med, Marcus Ctr, Atlanta, GA 30329 USA. [Woods, Douglas W.] Univ Wisconsin Milwaukee, Milwauke, WI USA. [Himle, Michael B.] Univ Utah, Salt Lake City, UT USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Piacentini, John C.] Univ Calif Los Angeles, Los Angeles, CA USA. [McNaught, Kevin] Tourette Syndrome Assoc, Bayside, NY USA. [Walkup, John T.] Weill Cornell Med Coll, New York, NY USA. [Mink, Jonathan W.] Univ Rochester, Sch Med, Rochester, NY USA. RP Scahill, L (reprint author), Emory Univ, Sch Med, Marcus Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA. EM lawrence.scahill@emory.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU National Institute of Mental Health (NIMH) [R01MH069874, 5R01MH069877, RO1MH069875, R01MH070802] FX This work was supported by grants from the National Institute of Mental Health (NIMH) to Lawrence Scahill (R01MH069874), Sabine Wilhelm (5R01MH069877), Alan L. Peterson (RO1MH069875), and John C. Piacentini (R01MH070802). NR 37 TC 22 Z9 23 U1 2 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG PY 2013 VL 28 IS 9 BP 1179 EP 1183 DI 10.1002/mds.25488 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 210KA UT WOS:000323830100005 PM 23681719 ER PT J AU Jafari, S Etminan, M Aminzadeh, F Samii, A AF Jafari, Siavash Etminan, Mahyar Aminzadeh, Farhad Samii, Ali TI Head injury and risk of Parkinson disease: A systematic review and meta-analysis SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; head injury; head trauma; traumatic brain injury; inflammation; meta-analysis; systematic review ID TRAUMATIC BRAIN-INJURY; ENVIRONMENTAL-FACTORS; YOUNG-ONSET; POPULATION; EPIDEMIOLOGY; HISTORY; LIFE AB Head trauma has been implicated in the etiopathogenesis of Parkinson's disease (PD). We performed a meta-analysis to investigate the association between head trauma and the risk of developing PD. We included observational studies if they (1) clearly defined PD, (2) defined head trauma leading to concussion, and (3) presented odds ratios (ORs) and 95% confidence intervals (CIs) or provided data to compute these statistics. Random effect model was used to estimate the pooled, adjusted OR. Heterogeneity between studies was evaluated with the Q test and the I-2 statistic. We conducted a sensitivity analysis to assess the influence of each study and repeated the analysis by excluding the studies with the largest weights. We used funnel plot to assess the presence of publication bias. After reviewing more than 636 article titles, 34 articles were selected for full review. In total, 22 studies (19 case-control studies, 2 nested case-control studies, and 1 cohort study) were included in the meta-analysis. The pooled OR for the association of PD and head trauma was 1.57 (95% CI, 1.35-1.83). The results of our meta-analysis indicate that a history of head trauma that results in concussion is associated with a higher risk of developing PD. (c) 2013 Movement Disorder Society C1 [Jafari, Siavash] Univ British Columbia, Fac Med, Sch Populat & Publ Hlth, Vancouver, BC, Canada. [Etminan, Mahyar] Univ British Columbia, Fac Med, Prov Hlth Serv, Therapeut Evaluat Unit, Vancouver, BC, Canada. [Aminzadeh, Farhad] St Georges Univ, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England. [Samii, Ali] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Samii, Ali] Vet Affairs Puget Sound Hlth Care Syst, Seattle Parkinson Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Samii, A (reprint author), Univ Washington, Vet Affairs Puget Hlth Care Syst, Seattle Parkinson Dis Res Educ & Clin Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM asamii@u.washington.edu NR 52 TC 31 Z9 32 U1 0 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG PY 2013 VL 28 IS 9 BP 1222 EP 1229 DI 10.1002/mds.25458 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 210KA UT WOS:000323830100015 PM 23609436 ER PT J AU Sung, VW Nicholas, AP AF Sung, Victor W. Nicholas, Anthony P. TI Nonmotor Symptoms in Parkinson's Disease Expanding the View of Parkinson's Disease Beyond a Pure Motor, Pure Dopaminergic Problem SO NEUROLOGIC CLINICS LA English DT Article DE Parkinson's disease; Nonmotor symptoms; Motor symptoms; Dopaminergic ID QUALITY STANDARDS SUBCOMMITTEE; SLEEP BEHAVIOR DISORDER; L-DOPA; AMERICAN-ACADEMY; PRACTICE PARAMETER; RATING-SCALES; REM-SLEEP; QUESTIONNAIRE; DEPRESSION; RECOMMENDATIONS AB Nonmotor symptoms (NMS) of Parkinson's disease (PD) are critical to identify and treat because of their impact on quality of life. Despite growing evidence of the importance of NMS on patients' quality of life, gaps remain in their recognition and treatment. The result is a need for increased information and understanding of specific NMS and the clinical approaches for their assessment and management in the context of PD as a whole. This article discusses the NMS of PD, their relationship to the pathologic basis of PD, and how NMS can be best managed. C1 [Sung, Victor W.; Nicholas, Anthony P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Sung, Victor W.; Nicholas, Anthony P.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Sung, VW (reprint author), Univ Alabama Birmingham, Dept Neurol, SC 360C,1720 7th Ave South, Birmingham, AL 35294 USA. EM vsung@uab.edu OI Sung, Victor/0000-0003-1024-3404 NR 78 TC 14 Z9 15 U1 1 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD AUG PY 2013 VL 31 IS 3 SU S BP S1 EP + DI 10.1016/j.ncl.2013.04.013 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 218PV UT WOS:000324445500002 PM 23931951 ER PT J AU Partridge, AH AF Partridge, Ann H. TI Cancer Survivorship and the Young Breast Cancer Patient: Addressing the Important Issues SO ONCOLOGIST LA English DT Editorial Material ID PREMATURE OVARIAN FAILURE; ADJUVANT CHEMOTHERAPY; MENOPAUSAL SYMPTOMS; WOMEN; FERTILITY C1 [Partridge, Ann H.] Dana Farber Canc Inst, Program Young Women Breast Canc, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 12 TC 4 Z9 4 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD AUG PY 2013 VL 18 IS 8 BP E19 EP E20 DI 10.1634/theoncologist.2013-0300 PG 2 WC Oncology SC Oncology GA 214AC UT WOS:000324101200001 PM 23986342 ER PT J AU Bonilla-Velez, J Mroz, EA Hammon, RJ Rocco, JW AF Bonilla-Velez, Juliana Mroz, Edmund A. Hammon, Rebecca J. Rocco, James W. TI Impact of Human Papillomavirus on Oropharyngeal Cancer Biology and Response to Therapy Implications for Treatment SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE HPV-positive oropharyngeal cancer; Clinical implications; Treatment implications ID SQUAMOUS-CELL CARCINOMA; PHASE-III TRIAL; NECK-CANCER; UNITED-STATES; CONCURRENT CHEMORADIATION; FUTURE-DIRECTIONS; CERVICAL-CANCER; HEAD; SURVIVAL; HPV AB Oropharyngeal squamous cell carcinoma (OPSCC) originating from human papillomavirus infection has emerged as a new entity in head and neck cancer, defining a subset of patients with distinct carcinogenesis, risk factor profiles, and clinical presentation that show markedly improved survival than patients with classic OPSCC. De-escalation of therapy and identification of relevant biomarkers to aid in patient selection are actively being investigated. This review addresses the implications of these findings in clinical care. C1 [Bonilla-Velez, Juliana; Hammon, Rebecca J.; Rocco, James W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rocco, JW (reprint author), Massachusetts Gen Hosp, Jackson 904G,55 Fruit St, Boston, MA 02114 USA. EM jrocco@partners.org FU Flight Attendant Medical Research Institute; NIH NIDCR [R01 DE022087]; NCI [R21 CA119591]; NIDCD [T32 DC000020]; AAO-HNSF Resident Research Award; Principles and Practice of Clinical Research and Latin American Initiative program, Harvard Medical School FX Funding Sources and Support: Flight Attendant Medical Research Institute; NIH NIDCR R01 DE022087; NCI R21 CA119591; NIDCD T32 DC000020; 2012 AAO-HNSF Resident Research Award; Principles and Practice of Clinical Research and Latin American Initiative program, Harvard Medical School. NR 69 TC 15 Z9 15 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 2013 VL 46 IS 4 BP 521 EP + DI 10.1016/j.otc.2013.04.009 PG 24 WC Otorhinolaryngology SC Otorhinolaryngology GA 214QI UT WOS:000324150000003 PM 23910468 ER PT J AU Hasegawa, K Tsugawa, Y Camargo, CA Hiraide, A Brown, DFM AF Hasegawa, Kohei Tsugawa, Yusuke Camargo, Carlos A., Jr. Hiraide, Atsushi Brown, David F. M. TI Regional variability in survival outcomes of out-of-hospital cardiac arrest: The All-Japan Utstein Registry SO RESUSCITATION LA English DT Article DE Out-of-hospital cardiac arrest; Epidemiology; Regional variation; Outcomes; Emergency medical service; Health services research ID AMERICAN-HEART-ASSOCIATION; AUSTRALIAN-RESUSCITATION-COUNCIL; ELEVATION MYOCARDIAL-INFARCTION; CARDIOPULMONARY-RESUSCITATION; COMATOSE SURVIVORS; STROKE-FOUNDATION; TASK-FORCE; CARE; MORTALITY; STATEMENT AB Objective: There is a paucity of studies on the degree of regional variability in out-of-hospital cardiac arrest (OHCA) outcomes, particularly in neurological outcome. This study aimed to determine whether there is a significant regional variation in survival outcomes of OHCA across Japan. Methods: We analyzed a prospective, nation-wide, population-based database (All-Japan Utstein Registry) involving all Japanese individuals who had non-traumatic OHCA resuscitated by emergency responders from January 2005 through December 2010. The primary study endpoint was favourable neurological survival at 1 month, defined as Cerebral Performance Category 1 or 2. We compared unadjusted and multivariable-adjusted rates of the outcome among seven geographic regions. Results: In the total catchment population of 128 million, there were 539,641 non-traumatic OHCA patients. Unadjusted neurologically favourable survival varied across regions from 1.9% to 3.1% (rate difference, 1.2%; 95% CI, 1.0-1.3%); the Northeast region had a significantly lower rate compared to the Midwest region (unadjusted rate ratio, 0.62; 95% CI, 0.60-0.64). This disparity became larger after adjusting for patient-and prehospital-level confounders (adjusted rate ratio, 0.52; 95% CI, 0.51-0.54). Among 35,153 OHCA patients with return of spontaneous circulation, unadjusted neurologically favourable survival varied from 26.4% to 34.7% (rate difference, 8.3%; 95% CI, 6.6-10.1%); the East region had a significantly lower rate compared to the Midwest region (adjusted rate ratio, 0.72; 95% CI, 0.68-0.76). Conclusion: In this prospective, nation-wide, population-based study in Japan, we found a two-fold regional difference in neurologically favourable survival after OHCA, suggesting regional disparities in prehospital care and in-hospital post-resuscitation care. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Hasegawa, Kohei; Camargo, Carlos A., Jr.; Brown, David F. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Tsugawa, Yusuke] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Tsugawa, Yusuke] St Lukes Life Sci Inst, Ctr Clin Epidemiol, Tokyo, Japan. [Hiraide, Atsushi] Kinki Univ, Fac Med, Dept Acute Med, Osaka, Japan. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Fire and Disaster Management Agency FX This study was supported in part by the grant for emergency management scientific research from the Fire and Disaster Management Agency (to Dr Hiraide, on behalf of the study group concerning strategy for applying the results of Utstein report for improvement of emergency service). The Fire and Disaster Management Agency gathered and managed the data but had no role in the design and conduct of the study; analysis and interpretation of the data; and preparation, review, or approval of the manuscript. NR 37 TC 34 Z9 37 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD AUG PY 2013 VL 84 IS 8 BP 1099 EP 1107 DI 10.1016/j.resuscitation.2013.03.007 PG 9 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 214BA UT WOS:000324103800030 PM 23499636 ER PT J AU Najita, JS Catalano, PJ AF Najita, Julie S. Catalano, Paul J. TI On Determining the BMD from Multiple Outcomes in Developmental Toxicity Studies when One Outcome is Intentionally Missing SO RISK ANALYSIS LA English DT Article DE Benchmark dose; dose-response modeling; fetal toxicity; subset selection ID QUANTITATIVE RISK-ASSESSMENT; LATENT VARIABLE MODELS; DOSE-RESPONSE MODEL; FETAL WEIGHT; TERATOLOGICAL EXPERIMENTS; REGRESSION-MODEL; CLUSTERED BINARY; LITTER SIZE; DISCRETE; TOXICOLOGY AB Public health concerns over the occurrence of developmental abnormalities that can occur as a result of prenatal exposure to drugs, chemicals, and other environmental factors has led to a number of developmental toxicity studies and the use of the benchmark dose (BMD) for risk assessment. To characterize risk from multiple sources, more recent analytic methods involve a joint modeling approach, accounting for multiple dichotomous and continuous outcomes. For some continuous outcomes, evaluating all subjects may not be feasible, and only a subset may be evaluated due to limited resources. The subset can be selected according to a prespecified probability model and the unobserved data can be viewed as intentionally missing in the sense that subset selection results in missingness that is experimentally planned. We describe a subset selection model that allows for sampling pups with malformations and healthy pups at different rates, and includes the well-known simple random sample (SRS) as a special case. We were interested in understanding how sampling rates that are selected beforehand influence the precision of the BMD. Using simulations we show how improvements over the SRS can be obtained by oversampling malformations, and how some sampling rates can yield precision that is substantially worse than the SRS. We also illustrate the potential for cost saving with oversampling. Simulations are based on a joint mixed effects model, and to account for subset selection, use of case weights to obtain valid dose-response estimates. C1 [Najita, Julie S.; Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Najita, Julie S.; Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Najita, JS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, MS CLS11007,450 Brookline Ave, Boston, MA 02215 USA. EM jnajita@jimmy.harvard.edu FU National Institute of Environmental Health Sciences of the U.S. National Institutes of Health [ES07142] FX The authors thank the reviewers for helpful comments that improved the article. This work was supported in part by grant ES07142 from the National Institute of Environmental Health Sciences of the U.S. National Institutes of Health. NR 31 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD AUG PY 2013 VL 33 IS 8 BP 1500 EP 1509 DI 10.1111/j.1539-6924.2012.01939.x PG 10 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 202IA UT WOS:000323206100013 PM 23231656 ER PT J AU Michaelson, MD Stadler, WM AF Michaelson, M. Dror Stadler, Walter M. TI Predictive Markers in Advanced Renal Cell Carcinoma SO SEMINARS IN ONCOLOGY LA English DT Review ID TARGETED THERAPY; CANCER; HYPERTENSION; SORAFENIB; SUNITINIB; BIOMARKER; SURVIVAL; TRIAL; PAZOPANIB; BEVACIZUMAB AB Predictive markers of response to therapy are increasingly important in advanced renal cell carcinoma (RCC) due to the proliferation of treatment options in recent years. Different types of potential predictive markers may include clinical, toxicity-based, serum, tissue, and radiologic biomarkers. Clinical factors are commonly used in overall prognostic models of RCC but have limited utility in predicting response to therapy. Correlation between development of particular toxicities and response to therapy has been noted, such as the correlation between hypertension and response to angiogenesis-targeted therapy. Serum and tissue biomarkers will be covered in detail elsewhere, but factors such as serum lactate dehydrogenase (LDH) and circulating cytokines show promise in this regard. Finally, baseline or early treatment radiology studies may have predictive ability for longer term efficacy, with most studies to date focusing on functional imaging modalities such as positron emission tomography (PET) scans, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), and DCE ultrasound (US). The ultimate goal of developing predictive biomarkers is to enable rational and personalized treatment strategies for patients with advanced RCC. (C) 2013 Elsevier Inc. All nights reserved. C1 [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stadler, Walter M.] Univ Chicago Med, Dept Med, Chicago, IL USA. [Stadler, Walter M.] Univ Chicago Med, Dept Surg, Chicago, IL USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dmichaelson1@partners.org NR 32 TC 10 Z9 10 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2013 VL 40 IS 4 BP 459 EP 464 DI 10.1053/j.seminonco1.2013.05.001 PG 6 WC Oncology SC Oncology GA 214QF UT WOS:000324149700007 PM 23972709 ER PT J AU McDermott, DF Atkins, MB AF McDermott, David F. Atkins, Michael B. TI Immune Therapy for Kidney Cancer: A Second Dawn? SO SEMINARS IN ONCOLOGY LA English DT Review ID RENAL-CELL CARCINOMA; DOSE RECOMBINANT INTERLEUKIN-2; RANDOMIZED CONTROLLED-TRIAL; CARBONIC-ANHYDRASE-IX; PHASE-III TRIAL; INTERFERON-ALPHA; SUBCUTANEOUS INTERLEUKIN-2; T-CELLS; IMMUNOTHERAPY; SUNITINIB AB Agents targeting the immune system have been a historical standard of care in metastatic renal cell carcinoma (RCC), but have largely been supplanted by newer targeted therapy. Recent insights into the regulation of an anti-tumor immune response has led to the development of agents that can activate immune responses primarily within the tumor, enabling the possibility of achieving durable tumor response in the absence of significant systemic toxicity. In addition, a better understanding of tumor immunology has raised the potential of developing predictive biomarkers of response to immunotherapy. Novel approaches including inhibition of immune checkpoints has entered clinical testing in RCC. (C) 2013 Elsevier Inc. All rights reserved. C1 [McDermott, David F.] Beth Israel Deaconess Med Ctr, Biol Therapy Program, Boston, MA 02215 USA. [McDermott, David F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [McDermott, David F.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Atkins, Michael B.] Georgetown Univ, Med Ctr, Georgetown Lombardi Comprehens Canc Ctr, Dept Oncol & Med, Washington, DC 20007 USA. RP McDermott, DF (reprint author), Beth Israel Deaconess Med Ctr, 375 Longwood Ave,MS-428, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU DF/HCC Renal Cancer SPORE [P50 CA101942-01] FX Supported in part by the DF/HCC Renal Cancer SPORE: P50 CA101942-01. NR 51 TC 6 Z9 7 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2013 VL 40 IS 4 BP 492 EP 498 DI 10.1053/j.seminonco1.2013.05.008 PG 7 WC Oncology SC Oncology GA 214QF UT WOS:000324149700011 PM 23972713 ER PT J AU Pongas, G Dasgupta, SK Thiagarajan, P AF Pongas, Georgios Dasgupta, Swapan Kumar Thiagarajan, Perumal TI Antiplatelet factor 4/heparin antibodies in patients with gram negative bacteremia SO THROMBOSIS RESEARCH LA English DT Article ID HEPARIN-INDUCED THROMBOCYTOPENIA; DEEP-VEIN THROMBOSIS; CHLAMYDIA-PNEUMONIAE; PLATELET ACTIVATION; IGG-SEROPOSITIVITY; SPONTANEOUS HIT; PLATELET-FACTOR-4; BINDING; COMPLICATIONS; PURIFICATION AB Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome of thrombocytopenia and prothrombotic state that follows exposure to heparin. However, spontaneous HIT has been described in the setting of infection, without evidence of previous heparin administration. Since PF4 binds to lipid A portion of lipopolysaccharide, we tested for the presence of antiPF4/heparin antibodies in patients with gram-negative bacteremia. Patients with bacteremia had higher titers of antiPF4/heparin antibodies compared to normal controls 26.3 +/- SD 34 units, N = 32 versus 6.3 +/- SD 2.38 units, N = 10, P = 0.001. FITC-labeled PF4 interacted with lipopolysaccharide in a concentration-dependent manner as determined by quenching of the emission spectrum following excitation at lambda 488. In addition, immunoaffinity purified antiPF4/Heparin antibodies from 3 patients with HIT cross-reacted with PF4/heparin complex. These results show that PF4/LPS complex is immunogenic and can elicit cross-reacting antibodies against PF4/Heparin, providing an explanation for the presence of these antibodies in individuals, who were never been exposed to heparin before. These antibodies may also be at least partly responsible for the thrombocytopenia associated with infection. Published by Elsevier Ltd. C1 [Pongas, Georgios; Thiagarajan, Perumal] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Dasgupta, Swapan Kumar] Baylor Coll Med, Dept Pathol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Thiagarajan, P (reprint author), Michael E DeBakey VA Med Ctr, Mail Stop 113,2002 Holcombe Blvd, Houston, TX 77030 USA. EM perumalt@bcm.edu OI Thiagarajan, Perumal/0000-0003-2186-7036 FU Department of Veterans Affairs; National Blood Foundation FX GP and PT designed and perform the experiments and wrote the paper. SKG isolated the PF4 and performed fluorescence measurements. This study was supported in part by grants from the Department of Veterans Affairs (to PT) and by a grant from the National Blood Foundation (to SKD). NR 26 TC 6 Z9 6 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD AUG PY 2013 VL 132 IS 2 BP 217 EP 220 DI 10.1016/j.thromres.2013.06.013 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 213LV UT WOS:000324059600028 PM 23830968 ER PT J AU Aston-Mourney, K Subramanian, SL Zraika, S Samarasekera, T Meier, DT Goldstein, LC Hull, RL AF Aston-Mourney, Kathryn Subramanian, Shoba L. Zraika, Sakeneh Samarasekera, Thanya Meier, Daniel T. Goldstein, Lynn C. Hull, Rebecca L. TI One year of sitagliptin treatment protects against islet amyloid-associated beta-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE DPP-4 inhibitor; IAPP; beta-cell mass; amyloid; exocrine pancreas pathology ID ENDOPLASMIC-RETICULUM STRESS; TRANSGENIC MOUSE; DIPEPTIDYL PEPTIDASE-4; GLYCEMIC CONTROL; DIABETES-MELLITUS; INCRETIN THERAPY; DPP-4 INHIBITOR; RODENT MODEL; POLYPEPTIDE; METFORMIN AB The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve beta-cell mass. However, sitagliptin also increases beta-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated beta-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing beta-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and beta-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, beta-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced beta-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates beta-cell secretion without increasing amyloid formation and protects against amyloid-induced beta-cell loss. This suggests a novel effect of sitagliptin to protect the beta-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas. C1 [Aston-Mourney, Kathryn; Subramanian, Shoba L.; Zraika, Sakeneh; Samarasekera, Thanya; Meier, Daniel T.; Hull, Rebecca L.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Aston-Mourney, Kathryn; Subramanian, Shoba L.; Zraika, Sakeneh; Samarasekera, Thanya; Meier, Daniel T.; Hull, Rebecca L.] Univ Washington, Seattle, WA 98195 USA. [Aston-Mourney, Kathryn] Deakin Univ, Sch Med, Metab Res Unit, Geelong, Vic 3217, Australia. [Goldstein, Lynn C.] PhenoPath Labs, Seattle, WA USA. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@uw.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K99-DK-080945, T32-DK-007247, P30-DK-017047]; University of Washington McAbee Fellowship; American Diabetes Association Mentor Award; Department of Veterans Affairs FX This work was supported by the Department of Veterans Affairs and National Institute of Diabetes and Digestive and Kidney Diseases grants, K99-DK-080945 (S. Zraika), T32-DK-007247, and P30-DK-017047 (Cellular and Molecular Imaging Core of the University of Washington Diabetes Research Center). K. Aston-Mourney was supported by the University of Washington McAbee Fellowship and an American Diabetes Association Mentor Award (to Dr. S. E. Kahn). NR 47 TC 19 Z9 20 U1 0 U2 7 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 AUG PY 2013 VL 305 IS 4 BP E475 EP E484 DI 10.1152/ajpendo.00025.2013 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 205GT UT WOS:000323432000002 PM 23736544 ER PT J AU Ferrari, G Nalassamy, N Downs, H Dana, R Oaklander, AL AF Ferrari, Giulio Nalassamy, Nambi Downs, Heather Dana, Reza Oaklander, Anne Louise TI Corneal innervation as a window to peripheral neuropathies SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE corneal nerves; peripheral neuropathy ID CONFOCAL MICROSCOPY; PACLITAXEL AB The cornea receives the densest sensory innervation of the body, which is exclusively from small-fiber nociceptive (pain-sensing) neurons. These are similar to those in the skin of the legs, the standard location for neurodiagnostic skin biopsies used to diagnose small-fiber peripheral polyneuropathies. Many cancer chemotherapy agents cause dose-related, therapy-limiting, sensory-predominant polyneuropathy. Because corneal innervation can be detected non-invasively, it is a potential surrogate biomarker for skin biopsy measurements. Therefore, we compared hindpaw-skin and cornea innervation in mice treated with neurotoxic chemotherapy. Paclitaxel (0, 5, 10, or 20 mg/kg) was administered to C57/Bl6 mice and peri-mortem cornea and skin biopsies were immunolabeled to reveal and permit quantitation of innervation. Both tissues demonstrated dose-dependent, highly correlated (r = 0.66) nerve fiber damage. These findings suggest that the quantification of corneal nerves may provide a useful surrogate marker for skin peripheral innervation. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Ferrari, Giulio; Nalassamy, Nambi; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Ferrari, Giulio] Ist Sci San Raffaele, I-20132 Milan, Italy. [Downs, Heather; Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Downs, Heather; Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ferrari, G (reprint author), Hosp San Raffaele, Eye Repair Lab, Cornea & Ocular Surface Unit, Via Olgettina 60, I-20122 Milan, Italy. EM giulio.ferrari@schepens.harvard.edu RI ferrari, giulio/J-9260-2016 OI ferrari, giulio/0000-0001-6474-9908 FU Public Health Service [NINDS K24-NS059892, NEI RO1-EY20889] FX Supported in part by the Public Health Service (NINDS K24-NS059892 and NEI RO1-EY20889). Presented in abstract form at the annual meetings of the Association for Research in Vision and Ophthalmology and the American Neurologic Association. NR 9 TC 9 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2013 VL 113 BP 148 EP 150 DI 10.1016/j.exer.2013.05.016 PG 3 WC Ophthalmology SC Ophthalmology GA 198OH UT WOS:000322931700019 PM 23769950 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Breast Cancer Treatment in the Era of Individualized Care Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM hburstein@partners.org NR 0 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2013 VL 27 IS 4 BP XIII EP XV DI 10.1016/j.hoc.2013.05.013 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 209ZB UT WOS:000323798000001 PM 23915750 ER PT J AU Stan, D Loprinzi, CL Ruddy, KJ AF Stan, Daniela Loprinzi, Charles L. Ruddy, Kathryn J. TI Breast Cancer Survivorship Issues SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Vasomotor symptoms; Sexual dysfunction; Infertility; Osteoporosis; Musculoskeletal pain; Cognitive changes; Neuropathy; Treatment-related cancers ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; ADJUVANT ENDOCRINE THERAPY; INDUCED PERIPHERAL NEUROPATHY; ACUTE MYELOID-LEUKEMIA; HOT FLASHES; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND; PHASE-III AB Survivors of breast cancer are confronted with a plethora of cancer treatment-related long-term symptoms, the most common being fatigue, hot flashes, sexual dysfunction, arthralgias, neuropathy, and cognitive dysfunction. Survivors of breast cancer also face cancer treatment-related disease states, such as osteoporosis, cardiac dysfunction, obesity, infertility, and secondary cancers. Evidence-based recommendations for screening, prevention, and early intervention should be implemented to improve quality of life and decrease comorbidities in this population. C1 [Stan, Daniela] Mayo Clin, Div Gen Internal Med, Rochester, MN 55905 USA. [Loprinzi, Charles L.] Mayo Clin, Rochester, MN 55905 USA. [Ruddy, Kathryn J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Stan, D (reprint author), Mayo Clin, Div Gen Internal Med, 200 1st St Southwest, Rochester, MN 55905 USA. EM stan.daniela@mayo.edu FU United States National Institutes of Health [CA 124477] FX Dr D. Stan: Internal Mayo Clinic funds; Dr C.L. Loprinzi: This work was supported by United States National Institutes of Health Grant-CA 124477; Dr K.J. Ruddy: Internal Dana Farber Cancer Institute funds. NR 146 TC 22 Z9 22 U1 0 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2013 VL 27 IS 4 BP 805 EP + DI 10.1016/j.hoc.2013.05.005 PG 24 WC Oncology; Hematology SC Oncology; Hematology GA 209ZB UT WOS:000323798000011 PM 23915746 ER PT J AU Hassett, MJ Elkin, EB AF Hassett, Michael J. Elkin, Elena B. TI What Does Breast Cancer Treatment Cost and What Is It Worth? SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Breast cancer; Cost; Value; Cost-effectiveness; Chemotherapy; Hospitalization ID IXABEPILONE PLUS CAPECITABINE; ADJUVANT CHEMOTHERAPY; UNITED-STATES; AROMATASE INHIBITORS; POSTMENOPAUSAL WOMEN; FEBRILE NEUTROPENIA; CONSERVING SURGERY; COLORECTAL-CANCER; ECONOMIC BURDEN; THERAPY AB The costs of breast cancer care are substantial and growing, and they extend across the spectrum of care. Medical therapies and hospitalizations account for a significant proportion of these costs. Cost-effectiveness analysis (CEA) is the preferred method for assessing the health benefits of medical interventions relative to their costs. Although many CEAs have been conducted for a wide range of breast cancer treatments, these analyses are not used routinely to guide coverage or utilization decisions in the United States. Currently, patients and providers may not consider costs when making most treatment decisions; this is likely to change as payment reform spreads. C1 [Hassett, Michael J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hassett, Michael J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, New York, NY 10065 USA. RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM michael_hassett@dfci.harvard.edu FU Cure; NCI; AHRQ FX Funding Sources: Dr M.J. Hassett: Susan G. Komen for the Cure, NCI, AHRQ. Dr E.B. Elkin: NO. NR 86 TC 3 Z9 3 U1 1 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2013 VL 27 IS 4 BP 829 EP + DI 10.1016/j.hoc.2013.05.011 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 209ZB UT WOS:000323798000012 PM 23915747 ER PT J AU Pineles, SL Suvak, MK Liverant, GI Gregor, K Wisco, BE Pitman, RK Orr, SP AF Pineles, Suzanne L. Suvak, Michael K. Liverant, Gabrielle I. Gregor, Kristin Wisco, Blair E. Pitman, Roger K. Orr, Scott P. TI Psychophysiologic Reactivity, Subjective Distress, and Their Associations With PTSD Diagnosis SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE PTSD; trauma cues; psychophysiology; self-reported distress; imagery ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY DISORDERS; COMBAT VETERANS; SEXUAL-ABUSE; IMAGERY; PSYCHOPATHOLOGY; WAR AB Intense subjective distress and physiologic reactivity upon exposure to reminders of the traumatic event are each diagnostic features of posttraumatic stress disorder (PTSD). However, subjective reports and psychophysiological data often suggest different conclusions. For the present study, we combined data from five previous studies to assess the contributions of these two types of measures in predicting PTSD diagnosis. One hundred fifty trauma-exposed participants who were classified into PTSD or non-PTSD groups based on structured diagnostic interviews completed the same script-driven imagery procedure, which quantified measures of psychophysiologic reactivity and self-reported emotional responses. We derived four discriminant functions (DiscFxs) that each maximally separated the PTSD from the non-PTSD group using (1) psychophysiologic measures recorded during personal mental imagery of the traumatic event; (2) self-report ratings in response to the trauma imagery; (3) psychophysiologic measures recorded during personal mental imagery of another highly stressful experience unrelated to the index traumatic event; and (4) self-report ratings in response to this other stressor. When PTSD status was simultaneously regressed on all four DiscFxs, trauma-related psychophysiological reactivity was a significant predictor, but physiological reactivity resulting from the highly stressful, but not traumatic script, was not. Self-reported distress to the traumatic experience and the other stressful event were both predictive of PTSD diagnosis. Trauma-related psychophysiologic reactivity was the best predictor of PTSD diagnosis, but self-reported distress contributed additional variance. These results are discussed in relation to the Research Domain Criteria framework. C1 [Pineles, Suzanne L.; Gregor, Kristin; Wisco, Blair E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Pineles, Suzanne L.; Liverant, Gabrielle I.; Gregor, Kristin; Wisco, Blair E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA USA. [Liverant, Gabrielle I.] VA Boston Healthcare Syst, Boston, MA USA. [Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pineles, SL (reprint author), VA Boston Healthcare Syst 116B 3, 150 South Huntington Ave, Boston, MA 02130 USA. EM Suzanne.Pineles@va.gov NR 37 TC 9 Z9 9 U1 4 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2013 VL 122 IS 3 BP 635 EP 644 DI 10.1037/a0033942 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 210CO UT WOS:000323807100003 PM 24016006 ER PT J AU Hilbert, A Hartmann, AS Czaja, J Schoebi, D AF Hilbert, Anja Hartmann, Andrea S. Czaja, Julia Schoebi, Dominik TI Natural Course of Preadolescent Loss of Control Eating SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE binge eating disorder; loss of control eating; depression; childhood; adolescence ID PRIMARY-SCHOOL CHILDREN; RISK-FACTORS; ADOLESCENT GIRLS; DISORDER EXAMINATION; CLINICAL-SIGNIFICANCE; BODY DISSATISFACTION; COMMUNITY SAMPLE; NEGATIVE AFFECT; ADULT OBESITY; WEIGHT-GAIN AB Cross-sectional evidence shows that loss of control (LOC) eating is a common and psychopathologically relevant experience in preadolescence. This study sought to investigate the natural course of preadolescent LOC eating in relation to psychopathology and body weight trajectory. A community sample of 55 children ages 8-13 years with LOC eating, defined as at least one episode of LOC eating within the past 3 months (LOC+), and 59 matched children without LOC history (LOC), were assessed with the Eating Disorder Examination adapted for Children and self-report questionnaires every 6 months over a 2-year follow-up. Of the LOC+ children, 54.5% of children remitted from LOC eating, 3.6% showed persistent LOC eating, and 41.8% showed recurring LOC eating over the follow-up period. Of the LOC children, 19% revealed an onset of LOC episodes, mostly with a low level of stability. Multilevel modeling showed that LOC eating predicted a partial binge eating disorder diagnosis and greater global eating disorder psychopathology, but not depressive symptoms or growth in body fatness. Between-person higher shape concern and weight-related teasing, as well as within-person decreases in shape concern and increases in depression, predicted a greater likelihood of subsequent LOC eating. The results indicate a moderate stability of LOC eating in preadolescent children, with prognostic significance for clinically relevant eating problems and eating disorder psychopathology. C1 [Hilbert, Anja] Univ Leipzig, Med Ctr, Integrated Res & Treatment Ctr AdiposityDis, Dept Med Psychol & Med Sociol, D-04103 Leipzig, Germany. [Hartmann, Andrea S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hartmann, Andrea S.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Czaja, Julia] Univ Marburg, Dept Psychol, D-35032 Marburg, Germany. [Schoebi, Dominik] Univ Fribourg, Dept Psychol, CH-1700 Fribourg, Switzerland. RP Hilbert, A (reprint author), Univ Leipzig, Med Ctr, Integrated Res & Treatment Ctr AdiposityDis, Dept Med Psychol & Med Sociol, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. EM anja.hilbert@medizin.uni-leipzig.de OI Schoebi, Dominik/0000-0003-3991-2712 NR 61 TC 23 Z9 23 U1 3 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2013 VL 122 IS 3 BP 684 EP 693 DI 10.1037/a0033330 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 210CO UT WOS:000323807100008 PM 24016009 ER PT J AU Jarosiewicz, B Masse, NY Bacher, D Cash, SS Eskandar, E Friehs, G Donoghue, JP Hochberg, LR AF Jarosiewicz, Beata Masse, Nicolas Y. Bacher, Daniel Cash, Sydney S. Eskandar, Emad Friehs, Gerhard Donoghue, John P. Hochberg, Leigh R. TI Advantages of closed-loop calibration in intracortical brain-computer interfaces for people with tetraplegia SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID PRIMATE MOTOR CORTEX; CORTICAL CONTROL; NEUROPROSTHETIC DEVICES; MACHINE INTERFACES; CELL DISCHARGE; NEURAL-CONTROL; ARM MOVEMENTS; NEURONS; ALGORITHM; DIRECTION AB Objective. Brain-computer interfaces (BCIs) aim to provide a means for people with severe motor disabilities to control their environment directly with neural activity. In intracortical BCIs for people with tetraplegia, the decoder that maps neural activity to desired movements has typically been calibrated using 'open-loop' (OL) imagination of control while a cursor automatically moves to targets on a computer screen. However, because neural activity can vary across contexts, a decoder calibrated using OL data may not be optimal for 'closed-loop' (CL) neural control. Here, we tested whether CL calibration creates a better decoder than OL calibration even when all other factors that might influence performance are held constant, including the amount of data used for calibration and the amount of elapsed time between calibration and testing. Approach. Two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial performed a center-out-back task using an intracortical BCI, switching between decoders that had been calibrated on OL versus CL data. Main results. Even when all other variables were held constant, CL calibration improved neural control as well as the accuracy and strength of the tuning model. Updating the CL decoder using additional and more recent data resulted in further improvements. Significance. Differences in neural activity between OL and CL contexts contribute to the superiority of CL decoders, even prior to their additional 'adaptive' advantage. In the near future, CL decoder calibration may enable robust neural control without needing to pause ongoing, practical use of BCIs, an important step toward clinical utility. C1 [Jarosiewicz, Beata; Masse, Nicolas Y.; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Jarosiewicz, Beata; Masse, Nicolas Y.; Bacher, Daniel; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. [Jarosiewicz, Beata; Donoghue, John P.; Hochberg, Leigh R.] Dept Vet Affairs Med Ctr, Rehabil R&D Serv, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Bacher, Daniel; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Cash, Sydney S.; Eskandar, Emad; Hochberg, Leigh R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Friehs, Gerhard] Rhode Isl Hosp, Dept Neurosurg, Providence, RI USA. RP Jarosiewicz, B (reprint author), Brown Univ, Dept Neurosci, 2 Stimson Ave,Box 1994, Providence, RI 02912 USA. EM beata@brown.edu OI Hochberg, Leigh/0000-0003-0261-2273 FU Craig H Neilsen Foundation fellowship; Rehabilitation R&D Service, Department of Veterans Affairs [B6453R, B6310N, B6459L, A6779I]; NIH: NIDCD [R01DC009899]; NINDS/NICHD [RC1HD063931]; NICHD-NCMRR [N01HD53403, N01HD10018]; NINDS-Javits [NS25074]; Doris Duke Charitable Foundation; MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Katie Samson Foundation FX The authors would like to thank participants S3 and T1 and their families, The Boston Home and their staff, and John Simeral, Sergey Stavisky, Katie Centrella, Erin Gallivan, and Etsub Berhanu for their contributions to this study. Thanks also to Michael Black for comments on an earlier draft of the manuscript, to Naveen Rao, Steven Chase, and Wasim Malik for useful discussions, and to Laurie Barefoot, Beth Travers, and David Rosler for research support. Funding was provided by the Craig H Neilsen Foundation fellowship (BJ); Rehabilitation R&D Service, Department of Veterans Affairs (Merit Review Awards: B6453R and A6779I, Career Development Transition Award: B6310N, Senior Research Career Scientist Award: B6459L); NIH: NIDCD (R01DC009899), NINDS/NICHD (RC1HD063931), NICHD-NCMRR (N01HD53403, N01HD10018), NINDS-Javits (NS25074); the Doris Duke Charitable Foundation; the MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; and the Katie Samson Foundation. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 59 TC 25 Z9 25 U1 0 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD AUG PY 2013 VL 10 IS 4 AR 046012 DI 10.1088/1741-2560/10/4/046012 PG 10 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 188UW UT WOS:000322221600019 PM 23838067 ER PT J AU Liberman, MY Ching, SN Chemali, J Brown, EN AF Liberman, Max Y. Ching, ShiNung Chemali, Jessica Brown, Emery N. TI A closed-loop anesthetic delivery system for real-time control of burst suppression SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID QUANTITATIVE EEG ANALYSIS; STATE-SPACE MODEL; BISPECTRAL INDEX; PERFORMANCE ASSESSMENT; PROPOFOL ANESTHESIA; FEEDBACK-CONTROL; REMIFENTANIL; SURGERY; HUMANS; FEASIBILITY AB Objective. There is growing interest in using closed-loop anesthetic delivery (CLAD) systems to automate control of brain states (sedation, unconsciousness and antinociception) in patients receiving anesthesia care. The accuracy and reliability of these systems can be improved by using as control signals electroencephalogram (EEG) markers for which the neurophysiological links to the anesthetic-induced brain states are well established. Burst suppression, in which bursts of electrical activity alternate with periods of quiescence or suppression, is a well-known, readily discernible EEG marker of profound brain inactivation and unconsciousness. This pattern is commonly maintained when anesthetics are administered to produce a medically-induced coma for cerebral protection in patients suffering from brain injuries or to arrest brain activity in patients having uncontrollable seizures. Although the coma may be required for several hours or days, drug infusion rates are managed inefficiently by manual adjustment. Our objective is to design a CLAD system for burst suppression control to automate management of medically-induced coma. Approach. We establish a CLAD system to control burst suppression consisting of: a two-dimensional linear system model relating the anesthetic brain level to the EEG dynamics; a new control signal, the burst suppression probability (BSP) defining the instantaneous probability of suppression; the BSP filter, a state-space algorithm to estimate the BSP from EEG recordings; a proportional-integral controller; and a system identification procedure to estimate the model and controller parameters. Main results. We demonstrate reliable performance of our system in simulation studies of burst suppression control using both propofol and etomidate in rodent experiments based on Vijn and Sneyd, and in human experiments based on the Schnider pharmacokinetic model for propofol. Using propofol, we further demonstrate that our control system reliably tracks changing target levels of burst suppression in simulated human subjects across different epidemiological profiles. Significance. Our results give new insights into CLAD system design and suggest a control-theory framework to automate second-to-second control of burst suppression for management of medically-induced coma. C1 [Liberman, Max Y.; Ching, ShiNung; Chemali, Jessica; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ching, ShiNung; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Liberman, MY (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM enb@neurostat.mit.edu FU NIH [DP1-OD003646, R01GM10498]; Burroughs-Wellcome Fund [1010625] FX This work was supported by: NIH Awards DP1-OD003646 and R01GM10498 (ENB), and the Burroughs-Wellcome Fund Award 1010625 (SC). NR 51 TC 11 Z9 12 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD AUG PY 2013 VL 10 IS 4 AR 046004 DI 10.1088/1741-2560/10/4/046004 PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 188UW UT WOS:000322221600011 PM 23744607 ER PT J AU Thompson, JW Forrester, MT Moseley, MA Foster, MW AF Thompson, J. Will Forrester, Michael T. Moseley, M. Arthur Foster, Matthew W. TI Solid-phase capture for the detection and relative quantification of S-nitrosoproteins by mass spectrometry SO METHODS LA English DT Review DE Nitric oxide; S-nitrosylation; S-nitrosothiol; Redox; Proteomics; Mass spectrometry; Nitrosative; Palmitoylation ID NITROSO-L-CYSTEINE; RESIN-ASSISTED CAPTURE; BIOTIN-SWITCH ASSAY; CYSTIC-FIBROSIS; ACCURATE MASS; NITRIC-OXIDE; NITROSYLATION; IDENTIFICATION; PROTEINS; PROTEOME AB The proteomic analysis of S-nitrosylated protein (SNO-proteins) has long depended on the biotin switch technique (BST), which requires blocking of free thiols, ascorbate-based denitrosylation of SNO-Cys, biotinylation of nascent thiol and avidin-based affinity isolation. A more recent development is resin assisted-capture of SNO-proteins (SNO-RAC), which substitutes thiopropyl Sepharose (TPS) for biotin-avidin, thus reducing the number of steps required for enrichment of S-nitrosylated proteins. In addition, SNO-RAC facilitates on-resin proteolytic digestion following SNO-protein capture, greatly simplifying the purification of peptides containing sites of S-nitrosylation ("SNO-sites"). This resin-based approach has also now been applied to detection of alternative Cys-based modifications, including S-palmitoylation (Acyl-RAC) and S-oxidation (Ox-RAC). Here, we review the important steps to minimize false-positive identification of SNO-proteins, give detailed methods for processing of protein-bound TPS for mass spectrometry (MS) based analysis, and discuss the various quantitative MS methods that are compatible with SNO-RAC. We also discuss strategies to overcome the current limitations surrounding MS-based SNO-site localization in peptides containing more than one potential target Cys residue. This article therefore serves as a starting point and guide for the MS-focused exploration of SNO-proteomes by SNO-RAC. (C) 2012 Elsevier Inc. All rights reserved. C1 [Thompson, J. Will; Moseley, M. Arthur] Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27710 USA. [Forrester, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Foster, Matthew W.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. RP Foster, MW (reprint author), Duke Univ, Med Ctr, Box 2629 Res Dr, Durham, NC 27710 USA. EM mwfoster@duke.edu FU National Institutes of Health [HL106121] FX This work was supported in part by a grant from the National Institutes of Health (HL106121). NR 55 TC 7 Z9 7 U1 4 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD AUG 1 PY 2013 VL 62 IS 2 BP 130 EP 137 DI 10.1016/j.ymeth.2012.10.001 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210WN UT WOS:000323865700003 PM 23064468 ER PT J AU Caruso, PA Johnson, J Thibert, R Rapalino, O Rincon, S Ratai, EM AF Caruso, Paul A. Johnson, Jason Thibert, Ron Rapalino, Otto Rincon, Sandra Ratai, Eva-Maria TI The Use of Magnetic Resonance Spectroscopy in the Evaluation of Epilepsy SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE H-1 MR spectroscopy; Epilepsy; Inborn error of metabolism; Focal cortical dysplasia ID AUTOMATED SPECTRAL-ANALYSIS; TEMPORAL-LOBE EPILEPSY; CREATINE TRANSPORTER DEFICIENCY; PROSPECTIVE MOTION CORRECTION; RESPIRATORY-CHAIN DEFECTS; PROTON NMR-SPECTROSCOPY; HUMAN-BRAIN INVIVO; MR SPECTROSCOPY; CHEMICAL-SHIFT; MITOCHONDRIAL DISORDERS AB Magnetic resonance spectroscopy (MRS) is indicated in the imaging protocol of the patient with epilepsy to screen for metabolic derangements such as inborn errors of metabolism and to characterize masses that may be equivocal on conventional magnetic resonance imaging for dysplasia versus neoplasia. Single-voxel MRS with echo time of 35 milliseconds may be used for this purpose as a quick screening tool in the epilepsy imaging protocol. MRS is useful in the evaluation of both focal and generalized epilepsy. C1 [Caruso, Paul A.; Johnson, Jason; Rapalino, Otto; Rincon, Sandra; Ratai, Eva-Maria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neuroradiol,Dept Radiol, Boston, MA 02114 USA. [Thibert, Ron] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Epilepsy Serv,Dept Neurol, Boston, MA 02114 USA. [Ratai, Eva-Maria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Caruso, PA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. EM pcaruso@partners.org NR 101 TC 7 Z9 7 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2013 VL 23 IS 3 BP 407 EP + DI 10.1016/j.nic.2012.12.012 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 209ZX UT WOS:000323800200006 PM 23928197 ER PT J AU Calkins, AS Iglehart, JD Lazaro, JB AF Calkins, Anne S. Iglehart, J. Dirk Lazaro, Jean-Bernard TI DNA damage-induced inhibition of rRNA synthesis by DNA-PK and PARP-1 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; POLYMERASE-I TRANSCRIPTION; POLY(ADP-RIBOSE) POLYMERASE; NUCLEOLAR PROTEIN; HISTONE CHAPERONE; ADP-RIBOSYLATION; BINDING-PROTEIN; KU ANTIGEN; CELL-CYCLE; PHOSPHORYLATION AB RNA synthesis and DNA replication cease after DNA damage. We studied RNA synthesis using an in situ run-on assay and found ribosomal RNA (rRNA) synthesis was inhibited 24 h after UV light, gamma radiation or DNA cross-linking by cisplatin in human cells. Cisplatin led to accumulation of cells in S phase. Inhibition of the DNA repair proteins DNA-dependent protein kinase (DNA-PK) or poly(ADP-ribose) polymerase 1 (PARP-1) prevented the DNA damage-induced block of rRNA synthesis. However, DNA-PK and PARP-1 inhibition did not prevent the cisplatin-induced arrest of cell cycle in S phase, nor did it induce de novo BrdU incorporation. Loss of DNA-PK function prevented activation of PARP-1 and its recruitment to chromatin in damaged cells, suggesting regulation of PARP-1 by DNA-PK within a pathway of DNA repair. From these results, we propose a sequential activation of DNA-PK and PARP-1 in cells arrested in S phase by DNA damage causes the interruption of rRNA synthesis after DNA damage. C1 [Calkins, Anne S.; Iglehart, J. Dirk; Lazaro, Jean-Bernard] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Lazaro, JB (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM jiglehart@partners.org; jlazaro@partners.org FU Pallotta Investigator Fund; Susan F. Smith Center for Women's Cancers; Marjorie Powell Allen Memorial Fund FX Pallotta Investigator Fund (to J.B.L.); the Susan F. Smith Center for Women's Cancers; the Marjorie Powell Allen Memorial Fund and Barbara and Paul Ferry. Funding for open access charge: The Pallotta Investigator Fund. NR 51 TC 15 Z9 17 U1 1 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG PY 2013 VL 41 IS 15 BP 7378 EP 7386 DI 10.1093/nar/gkt502 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212GL UT WOS:000323970700024 PM 23775790 ER PT J AU Chen, EY Dobrinski, KP Brown, KH Clagg, R Edelman, E Ignatius, MS Chen, JYH Brockmann, J Nielsen, GP Ramaswamy, S Keller, C Lee, C Langenau, DM AF Chen, Eleanor Y. Dobrinski, Kimberly P. Brown, Kim H. Clagg, Ryan Edelman, Elena Ignatius, Myron S. Chen, Jin Yun Helen Brockmann, Jillian Nielsen, G. Petur Ramaswamy, Sridhar Keller, Charles Lee, Charles Langenau, David M. TI Cross-Species Array Comparative Genomic Hybridization Identifies Novel Oncogenic Events in Zebrafish and Human Embryonal Rhabdomyosarcoma SO PLOS GENETICS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSGENIC ZEBRAFISH; RAS GENES; PHASE-II; CYCLIN D; CANCER; TUMORS; CELLS; EXPRESSION AB Human cancer genomes are highly complex, making it challenging to identify specific drivers of cancer growth, progression, and tumor maintenance. To bypass this obstacle, we have applied array comparative genomic hybridization (array CGH) to zebrafish embryonal rhabdomyosaroma (ERMS) and utilized cross-species comparison to rapidly identify genomic copy number aberrations and novel candidate oncogenes in human disease. Zebrafish ERMS contain small, focal regions of low-copy amplification. These same regions were commonly amplified in human disease. For example, 16 of 19 chromosomal gains identified in zebrafish ERMS also exhibited focal, low-copy gains in human disease. Genes found in amplified genomic regions were assessed for functional roles in promoting continued tumor growth in human and zebrafish ERMS - identifying critical genes associated with tumor maintenance. Knockdown studies identified important roles for Cyclin D2 (CCND2), Homeobox Protein C6 (HOXC6) and PlexinA1 (PLXNA1) in human ERMS cell proliferation. PLXNA1 knockdown also enhanced differentiation, reduced migration, and altered anchorage-independent growth. By contrast, chemical inhibition of vascular endothelial growth factor (VEGF) signaling reduced angiogenesis and tumor size in ERMS-bearing zebrafish. Importantly, VEGFA expression correlated with poor clinical outcome in patients with ERMS, implicating inhibitors of the VEGF pathway as a promising therapy for improving patient survival. Our results demonstrate the utility of array CGH and cross-species comparisons to identify candidate oncogenes essential for the pathogenesis of human cancer. C1 [Chen, Eleanor Y.; Clagg, Ryan; Ignatius, Myron S.; Brockmann, Jillian; Langenau, David M.] Massachusetts Gen Hosp, Div Mol Pathol, Charlestown, MA 02129 USA. [Chen, Eleanor Y.; Clagg, Ryan; Ignatius, Myron S.; Langenau, David M.] Harvard Stem Cell Inst, Boston, MA USA. [Chen, Eleanor Y.; Clagg, Ryan; Edelman, Elena; Ignatius, Myron S.; Ramaswamy, Sridhar; Langenau, David M.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Chen, Eleanor Y.; Dobrinski, Kimberly P.; Brown, Kim H.; Ignatius, Myron S.; Chen, Jin Yun Helen; Ramaswamy, Sridhar; Lee, Charles; Langenau, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Dobrinski, Kimberly P.; Brown, Kim H.; Chen, Jin Yun Helen; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dobrinski, Kimberly P.] Univ S Florida, Coll Med, Dept Pathol & Cell Biol, Tampa, FL USA. [Brown, Kim H.] Portland State Univ, Dept Biol, Portland, OR 97207 USA. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Keller, Charles] Oregon Hlth & Sci Univ, Dept Pediat, Pediat Canc Biol Program, Portland, OR 97201 USA. RP Chen, EY (reprint author), Massachusetts Gen Hosp, Div Mol Pathol, Charlestown, MA 02129 USA. EM dlangenau@partners.org FU NIH [K01 AR055619, RO1 CA154923, R21 CA156056, K08 AR063165-01]; Alex's Lemonade Stand Foundation (ALSF); American Cancer Society; Harvard Stem Cell Institute; St. Baldrick's Foundation Scholar Award; NIH-National Institute of Environmental Health Sciences [K99/R00 ES018892]; "A'' ALSF ward; NIH-National Cancer Institute [5R01CA111560]; NIH-National Human Genome Research Institute [5P41HG004421] FX DML was supported by NIH grants K01 AR055619, RO1 CA154923, and R21 CA156056, the Alex's Lemonade Stand Foundation (ALSF), the American Cancer Society, and the Harvard Stem Cell Institute. EYC was supported by NIH K08 AR063165-01 and St. Baldrick's Foundation Scholar Award. KHB was supported by Grant K99/R00 ES018892 (NIH-National Institute of Environmental Health Sciences). MSI was supported by an "A'' ALSF ward. CL is supported by Grants 5R01CA111560 (NIH-National Cancer Institute) and 5P41HG004421 (NIH-National Human Genome Research Institute). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 49 TC 14 Z9 14 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2013 VL 9 IS 8 AR e1003727 DI 10.1371/journal.pgen.1003727 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 210KB UT WOS:000323830300069 PM 24009521 ER PT J AU He, X Sanders, SJ Liu, L De Rubeis, S Lim, ET Sutcliffe, JS Schellenberg, GD Gibbs, RA Daly, MJ Buxbaum, JD State, MW Devlin, B Roeder, K AF He, Xin Sanders, Stephan J. Liu, Li De Rubeis, Silvia Lim, Elaine T. Sutcliffe, James S. Schellenberg, Gerard D. Gibbs, Richard A. Daly, Mark J. Buxbaum, Joseph D. State, Matthew W. Devlin, Bernie Roeder, Kathryn TI Integrated Model of De Novo and Inherited Genetic Variants Yields Greater Power to Identify Risk Genes SO PLOS GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; COPY-NUMBER VARIATION; FUNCTIONAL IMPACT; RARE VARIANTS; MUTATIONS; ASSOCIATION; DISEASE; DISCOVERY; COL25A1; EXOMES AB De novo mutations affect risk for many diseases and disorders, especially those with early-onset. An example is autism spectrum disorders (ASD). Four recent whole-exome sequencing (WES) studies of ASD families revealed a handful of novel risk genes, based on independent de novo loss-of-function (LoF) mutations falling in the same gene, and found that de novo LoF mutations occurred at a twofold higher rate than expected by chance. However successful these studies were, they used only a small fraction of the data, excluding other types of de novo mutations and inherited rare variants. Moreover, such analyses cannot readily incorporate data from case-control studies. An important research challenge in gene discovery, therefore, is to develop statistical methods that accommodate a broader class of rare variation. We develop methods that can incorporate WES data regarding de novo mutations, inherited variants present, and variants identified within cases and controls. TADA, for Transmission And De novo Association, integrates these data by a gene-based likelihood model involving parameters for allele frequencies and gene-specific penetrances. Inference is based on a Hierarchical Bayes strategy that borrows information across all genes to infer parameters that would be difficult to estimate for individual genes. In addition to theoretical development we validated TADA using realistic simulations mimicking rare, large-effect mutations affecting risk for ASD and show it has dramatically better power than other common methods of analysis. Thus TADA's integration of various kinds of WES data can be a highly effective means of identifying novel risk genes. Indeed, application of TADA to WES data from subjects with ASD and their families, as well as from a study of ASD subjects and controls, revealed several novel and promising ASD candidate genes with strong statistical support. C1 [He, Xin; Roeder, Kathryn] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Sanders, Stephan J.; State, Matthew W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sanders, Stephan J.; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Liu, Li; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [De Rubeis, Silvia; Buxbaum, Joseph D.] Icahn Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY USA. [De Rubeis, Silvia; Buxbaum, Joseph D.] Icahn Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Lim, Elaine T.; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lim, Elaine T.; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Lim, Elaine T.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Sutcliffe, James S.] Vanderbilt Univ, Dept Psychiat, Vanderbilt Brain Inst, Nashville, TN 37235 USA. [Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Buxbaum, Joseph D.] Icahn Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Buxbaum, Joseph D.] Icahn Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP He, X (reprint author), Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. EM roeder@stat.cmu.edu RI Liu, Li/G-1897-2015; De Rubeis, Silvia/E-9852-2013; OI De Rubeis, Silvia/0000-0001-9383-6883; Sutcliffe, James/0000-0001-5200-6007; Buxbaum, Joseph/0000-0001-8898-8313; Sanders, Stephan/0000-0001-9112-5148 FU NIH [R01MH089208, R01 MH089025, R01 MH089004, R01MH089175, R01 MH089482, RO1 MH057881, R01 MH061009, 1U01MH100233-01, 1U01MH100209] FX This work was directly supported by NIH grants R01MH089208 (MJD), R01 MH089025 (JDB), R01 MH089004 (GDS), R01MH089175 (RAG), R01 MH089482 (JSS), RO1 MH057881 (BD), R01 MH061009 (JSS), 1U01MH100233-01 (JDB), and 1U01MH100209 (BD). This work was also supported by a grant from the Simons Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 50 Z9 50 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2013 VL 9 IS 8 AR e1003671 DI 10.1371/journal.pgen.1003671 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 210KB UT WOS:000323830300023 PM 23966865 ER PT J AU Ibrahim, MK Barnes, JL Anstead, GM Jimenez, F Travi, BL Peniche, AG Osorio, EY Ahuja, SS Melby, PC AF Ibrahim, Marwa K. Barnes, Jeffrey L. Anstead, Gregory M. Jimenez, Fabio Travi, Bruno L. Peniche, Alex G. Osorio, E. Yaneth Ahuja, Seema S. Melby, Peter C. TI The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID PROTEIN-ENERGY MALNUTRITION; BONE-MARROW-CELLS; IMMUNE-RESPONSE; MALNOURISHED RATS; DENDRITIC CELLS; SOUTHERN SUDAN; RISK-FACTOR; KALA-AZAR; INFECTION; NUTRITION AB In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4-5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c(+) dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2(+) macrophages, and CD169(+) subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system. C1 [Ibrahim, Marwa K.; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ibrahim, Marwa K.; Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Ahuja, Seema S.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Travi, Bruno L.; Peniche, Alex G.; Osorio, E. Yaneth; Melby, Peter C.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA. [Travi, Bruno L.; Melby, Peter C.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Travi, Bruno L.; Melby, Peter C.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Travi, Bruno L.; Melby, Peter C.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. RP Ibrahim, MK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. EM pcmelby@utmb.edu OI Ibrahim, Marwa/0000-0002-2603-8280 NR 67 TC 4 Z9 4 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD AUG PY 2013 VL 7 IS 8 AR e2329 DI 10.1371/journal.pntd.0002329 PG 16 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 211WE UT WOS:000323941500008 PM 23967356 ER PT J AU Salloum, S Wang, HL Ferguson, C Parton, RG Tai, AW AF Salloum, Shadi Wang, Hongliang Ferguson, Charles Parton, Robert G. Tai, Andrew W. TI Rab18 Binds to Hepatitis C Virus NS5A and Promotes Interaction between Sites of Viral Replication and Lipid Droplets SO PLOS PATHOGENS LA English DT Article ID NONSTRUCTURAL PROTEIN 5A; 4-KINASE III ALPHA; CELL-CULTURE SILAC; RNA REPLICATION; CORE PROTEIN; IN-VITRO; EFFICIENT REPLICATION; DIRECT VISUALIZATION; INFECTIOUS VIRUS; AMINO-ACIDS AB Hepatitis C virus (HCV) is a single-stranded RNA virus that replicates on endoplasmic reticulum-derived membranes. HCV particle assembly is dependent on the association of core protein with cellular lipid droplets (LDs). However, it remains uncertain whether HCV assembly occurs at the LD membrane itself or at closely associated ER membranes. Furthermore, it is not known how the HCV replication complex and progeny genomes physically associate with the presumed sites of virion assembly at or near LDs. Using an unbiased proteomic strategy, we have found that Rab18 interacts with the HCV nonstructural protein NS5A. Rab18 associates with LDs and is believed to promote physical interaction between LDs and ER membranes. Active (GTP-bound) forms of Rab18 bind more strongly to NS5A than a constitutively GDP-bound mutant. NS5A colocalizes with Rab18-positive LDs in HCV-infected cells, and Rab18 appears to promote the physical association of NS5A and other replicase components with LDs. Modulation of Rab18 affects genome replication and possibly also the production of infectious virions. Our results support a model in which specific interactions between viral and cellular proteins may promote the physical interaction between membranous HCV replication foci and lipid droplets. C1 [Salloum, Shadi; Wang, Hongliang; Tai, Andrew W.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Ferguson, Charles; Parton, Robert G.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. [Ferguson, Charles; Parton, Robert G.] Univ Queensland, Ctr Microscopy & Microanal, Brisbane, Qld, Australia. [Tai, Andrew W.] Ann Arbor Vet Adm Hlth Syst, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. RP Salloum, S (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM andrewwt@med.umich.edu OI Parton, Robert/0000-0002-7494-5248; Tai, Andrew/0000-0002-6877-450X FU National Institutes of Health [AI083785, DK097374]; Michigan Gastrointestinal Peptide Research Center [NIDDK 5P30DK034933]; Greenview Foundation Hepatitis C Research Fund; National Health and Medical Research Council of Australia [569542, 511005] FX This work was supported by grants AI083785 and DK097374 from the National Institutes of Health, the Michigan Gastrointestinal Peptide Research Center (NIDDK 5P30DK034933), and the Greenview Foundation Hepatitis C Research Fund (to AWT), as well as by a fellowship (no. 569542) and grant (no. 511005) from the National Health and Medical Research Council of Australia (to RGP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 41 Z9 41 U1 1 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD AUG PY 2013 VL 9 IS 8 AR e1003513 DI 10.1371/journal.ppat.1003513 PG 16 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 211EQ UT WOS:000323888200017 PM 23935497 ER PT J AU Kubicki, M Shenton, ME Maciejewski, PK Pelavin, PE Hawley, KJ Ballinger, T Swisher, T Jabbar, GA Thermenos, HW Keshavan, MS Seidman, LJ DeLisi, LE AF Kubicki, M. Shenton, M. E. Maciejewski, P. K. Pelavin, P. E. Hawley, K. J. Ballinger, T. Swisher, T. Jabbar, G. A. Thermenos, H. W. Keshavan, M. S. Seidman, L. J. DeLisi, L. E. TI Decreased axial diffusivity within language connections: A possible biomarker of schizophrenia risk SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Increased familial risk; Schizophrenia; Diffusion tensor imaging; White matter maturation ID HIGH GENETIC RISK; WHITE-MATTER MICROSTRUCTURE; ULTRA-HIGH-RISK; RADIAL DIFFUSIVITY; HUMAN BRAIN; 1ST-EPISODE SCHIZOPHRENIA; MULTIPLE-SCLEROSIS; TRACTOGRAPHY; PSYCHOSIS; MRI AB Siblings of patients diagnosed with schizophrenia are at elevated risk for developing this disorder. The nature of such risk associated with brain abnormalities, and whether such abnormalities are similar to those observed in schizophrenia, remain unclear. Deficits in language processing are frequently reported in increased risk populations. Interestingly, white matter pathology involving fronto-temporal language pathways, including arcuate fasciculus (AF), uncinate fasciculus (UF), and inferior occipitofrontal fasciculus (IOFF), are frequently reported in schizophrenia. In this study, high spatial and directional resolution diffusion MRI data was obtained on a 3 T magnet from 33 subjects with increased familial risk for developing schizophrenia, and 28 control subjects. Diffusion tractography was performed to measure white matter integrity within AF, UF, and IOFF. To understand these abnormalities, Fractional Anisotropy (FA, a measure of tract integrity) and Trace (a measure of overall diffusion), were combined with more specific measures of axial diffusivity (AX, a putative measure of axonal integrity) and radial diffusivity (RD, a putative measure of myelin integrity). Results revealed a significant decrease in Trace within IOFF, and a significant decrease in AX in all tracts. FA and RD anomalies, frequently reported in schizophrenia, were not observed. Moreover, AX group effect was modulated by age, with increased risk subjects demonstrating a deviation from normal maturation trajectory. Findings suggest that familial risk for schizophrenia may be associated with abnormalities in axonal rather than myelin integrity, and possibly associated with disruptions in normal brain maturation. AX should be considered a possible biomarker of risk for developing schizophrenia. (C) 2013 Elsevier B. V. All rights reserved. C1 [Kubicki, M.; Shenton, M. E.; Pelavin, P. E.; Hawley, K. J.; Ballinger, T.; Swisher, T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Shenton, M. E.; DeLisi, L. E.] VA Boston Healthcare Syst, Brockton, MA USA. [Maciejewski, P. K.; Jabbar, G. A.; Thermenos, H. W.; Keshavan, M. S.; Seidman, L. J.; DeLisi, L. E.] Harvard Univ, Sch Med, Boston, MA USA. [Seidman, L. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Thermenos, H. W.; Keshavan, M. S.; Seidman, L. J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Thermenos, H. W.; Keshavan, M. S.; Seidman, L. J.] Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02115 USA. RP Kubicki, M (reprint author), Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA. EM kubicki@bwh.harvard.edu FU National Alliance for Medical Image Computing (NA-MIC); National Institutes of Health Roadmap for Medical Research [U54 EB005149]; VA Merit; National Institute of Health [R01 MH 074794]; [NIMH-R21MH083205]; [MH 64023] FX This study was supported, in part, by the National Alliance for Medical Image Computing (NA-MIC), supported through the National Institutes of Health Roadmap for Medical Research, Grant U54 EB005149 (MK, CFW, PG); VA Merit (MS); National Institute of Health (R01 MH 074794 to CFW and MK); NIMH-R21MH083205 (LED); and MH 64023 (MSK, LS). NR 60 TC 12 Z9 14 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2013 VL 148 IS 1-3 BP 67 EP 73 DI 10.1016/j.schres.2013.06.014 PG 7 WC Psychiatry SC Psychiatry GA 211UL UT WOS:000323936600011 PM 23800617 ER PT J AU Woods, SW Addington, J Bearden, CE Cadenhead, KS Cannon, TD Cornblatt, BA Mathalon, DH Perkins, DO Seidman, LJ Tsuang, MT Walker, EF McGlashan, TH AF Woods, Scott W. Addington, Jean Bearden, Carrie E. Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara A. Mathalon, Daniel H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. McGlashan, Thomas H. TI Psychotropic medication use in youth at high risk for psychosis: Comparison of baseline data from two research cohorts 1998-2005 and 2008-2011 SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Psychosis; High risk; Risk syndrome; Psychotropic medication; Antipsychotic medication ID RANDOMIZED CONTROLLED-TRIAL; ANTIPSYCHOTIC MEDICATIONS; PRODROMAL SYMPTOMS; 2ND-GENERATION ANTIPSYCHOTICS; PREDICTIVE-VALIDITY; META-ANALYSIS; INTERRATER RELIABILITY; EPISODE PSYCHOSIS; YOUNG-PEOPLE; 1ST EPISODE AB Background: Antipsychotic medication use rates have generally been rising among youth with psychiatric disorders, but little is known about use rates of antipsychotics or other psychotropic medications in patients at high risk for psychosis. Method: Baseline psychotropic medication use rates were compared in two research cohorts of patients at high risk for psychosis that enrolled between 1998-2005 (n = 391) and 2008-2011 (n = 346). Treatment durations and antipsychotic doses were described for cohort 2. Results: Median age was 17 years in cohort 1 and 18 years in cohort 2. The rate of prescription of any psychotropic at baseline was roughly 40% for each cohort. Antipsychotic prescription rates were 24% among sites that permitted baseline antipsychotic use in cohort 1 and 18% in the cohort 2; the decline did not quite reach statistical significance (p = 0.064). In cohort 2 the mean +/- SD baseline chlorpromazine-equivalent dose was 121 +/- 108 mg/d, and lifetime duration of antipsychotic treatment was 3.8 +/- 5.9 months. Discussion: Although the rate of antipsychotic prescription among high-risk youth may have fallen slightly, the nearly one-in-five rate in the second cohort still constitutes a significant exposure. Mitigating factors were that doses and durations of treatment were low. As for other nonpsychotic conditions, it is incumbent on our field to develop alternative treatments for high-risk patients and to generate additional evidence for or against the efficacy of antipsychotics to help define their appropriate role if alternative treatments fail. (C) 2013 Elsevier B. V. All rights reserved. C1 [Woods, Scott W.; McGlashan, Thomas H.] Yale Univ, Dept Psychiat, New Haven, CT 06519 USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB T2N 1N4, Canada. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA USA. [Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT 06519 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Mathalon, Daniel H.] UCSF, Dept Psychiat, San Francisco, CA USA. [Perkins, Diana O.] UCSF, Univ N Carolina, Dept Psychiat, San Francisco, CA USA. [Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Gen Hosp, Dept Psychiat,Med Sch, Boston, MA 02215 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP Woods, SW (reprint author), Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, 34 Pk St, New Haven, CT 06519 USA. EM scott.woods@yale.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU National Institute of Mental Health [U01 MH066160, U01 MH082022, U01 MH066134, U01 MH081984, U01 MH060720, R01 MH60720, U01 MH081944, K24 MH76191, U01 MH065079, MH081902, U01 MH061523, U01 MH081857, U01 MH066069, U01 MH082004, U01 MH065562, U01 MH081928, P50 MH080272]; National Institute of Mental Health (Commonwealth of Massachusetts) [SCDMH82101008006, U01 MH062066, U01 MH081988] FX This study was supported by the National Institute of Mental Health (grants U01 MH066160 and U01 MH082022 to Dr Woods; grants U01 MH066134 and U01 MH081984 to Dr Addington; grants U01 MH060720, R01 MH60720, U01 MH081944 and K24 MH76191 to Dr Cadenhead; grants U01 MH065079 and MH081902 to Dr Cannon; grants U01 MH061523 and U01 MH081857 to Dr Cornblatt; grants U01 MH066069 and U01 MH082004 to Dr Perkins; grants U01 MH065562, U01 MH081928, P50 MH080272 and Commonwealth of Massachusetts SCDMH82101008006 to Dr Seidman; and grants U01 MH062066 to EFW and U01 MH081988 to Dr Walker). The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 55 TC 14 Z9 14 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2013 VL 148 IS 1-3 BP 99 EP 104 DI 10.1016/j.schres.2013.05.019 PG 6 WC Psychiatry SC Psychiatry GA 211UL UT WOS:000323936600016 PM 23787224 ER PT J AU Amato, RJ Felts, AS Rodriguez, AL Venable, DF Morrison, RD Byers, FW Daniels, JS Niswender, CM Conn, PJ Lindsley, CW Jones, CK Emmitte, KA AF Amato, Russell J. Felts, Andrew S. Rodriguez, Alice L. Venable, Daryl F. Morrison, Ryan D. Byers, Frank W. Daniels, J. Scott Niswender, Colleen M. Conn, P. Jeffrey Lindsley, Craig W. Jones, Carrie K. Emmitte, Kyle A. TI Substituted 1-Phenyl-3-(pyridin-2-yl)urea Negative Allosteric Modulators of mGlu(5): Discovery of a New Tool Compound VU0463841 with Activity in Rat Models of Cocaine Addiction SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE mGlu(5); negative allosteric modulator; noncompetitive antagonist; CNS; cocaine; addiction ID METABOTROPIC GLUTAMATE RECEPTORS; MGLUR5 ANTAGONIST MPEP; 2-METHYL-6-(PHENYLETHYNYL)-PYRIDINE MPEP; SQUIRREL-MONKEYS; DRUG DISCOVERY; CNS EXPOSURE; PHARMACOLOGY; SEEKING; REWARD; POTENT AB Cocaine is a powerful and highly addictive stimulant that disrupts the normal reward circuitry in the central nervous system (CNS), producing euphoric effects. Cocaine use can lead to acute and life threatening emergencies, and abuse is associated with increased risk for contracting infectious diseases. Though certain types of behavioral therapy have proven effective for treatment of cocaine addiction, relapse remains high, and there are currently no approved medications for the treatment of cocaine abuse. Evidence has continued to accumulate that indicates a critical role for the metabotropic glutamate receptor subtype 5 (mGlu(5)) in the modulation of neural circuitry associated with the addictive properties of cocaine. While the small molecule mGlu(5) negative allosteric modulator (NAM) field is relatively advanced, investigation into the potential of small molecule mGlu(5) NAMs for the treatment of cocaine addiction remains an area of high interest. Herein we describe the discovery and characterization of a potent and selective compound 29 (VU0463841) with good CNS exposure in rats. The utility of 29 (VU0463841) was demonstrated by its ability to attenuate drug seeking behaviors in relevant rat models of cocaine addiction. C1 [Amato, Russell J.; Felts, Andrew S.; Rodriguez, Alice L.; Venable, Daryl F.; Morrison, Ryan D.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Jones, Carrie K.; Emmitte, Kyle A.] Vanderbilt Univ Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. [Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ Sch Med, Dept Chem, Nashville, TN 37232 USA. [Amato, Russell J.; Felts, Andrew S.; Rodriguez, Alice L.; Venable, Daryl F.; Morrison, Ryan D.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Jones, Carrie K.; Emmitte, Kyle A.] Vanderbilt Univ Sch Med, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. RP Jones, CK (reprint author), Vanderbilt Univ Sch Med, Vanderbilt Ctr Neurosci Drug Discovery, 1205 Light Hall, Nashville, TN 37232 USA. EM carrie.jones@vanderbilt.edu; kyle.a.emmitte@vanderbilt.edu FU NIH; NIMH; NIDA [R01 DA023947]; Alzheimer's Association; Bristol-Myers Squibb; AstraZeneca; Tennessee Valley Healthcare System (U.S. Dept. of Veteran's Affairs); NINDS; Seaside Therapeutics [VUMC33842] FX C.W.L. receives funding from NIH, NIMH, NIDA, the Alzheimer's Association, Bristol-Myers Squibb, and AstraZeneca. C.K.J. receives funding from NIMH and Tennessee Valley Healthcare System (U.S. Dept. of Veteran's Affairs), Bristol-Myers Squibb, and AstraZeneca. C.M.N. receives funding from NINDS, Bristol-Myers Squibb, and AstraZeneca. P.J.C. receives funding from NIH, NIMH, NINDS, Bristol-Myers Squibb, and AstraZeneca. K.A.E. receives funding from NIMH. The authors thank NIDA (R01 DA023947) and Seaside Therapeutics (VUMC33842) for their support of our programs in the development of mGlu5 NAMs. NR 58 TC 8 Z9 8 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD AUG PY 2013 VL 4 IS 8 BP 1217 EP 1228 DI 10.1021/cn400070k PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 206PZ UT WOS:000323535900010 PM 23682684 ER PT J AU Rifkin, DE Katz, R Chonchol, M Shlipak, MG Sarnak, MJ Fried, LF Newman, AB Siscovick, DS Peralta, CA AF Rifkin, Dena E. Katz, Ronit Chonchol, Michel Shlipak, Michael G. Sarnak, Mark J. Fried, Linda F. Newman, Anne B. Siscovick, David S. Peralta, Carmen A. TI Blood Pressure Components and Decline in Kidney Function in Community-Living Older Adults: The Cardiovascular Health Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; cystatin C; diastolic blood pressure; elderly; hypertension; kidney function; systolic blood pressure ID ISOLATED SYSTOLIC HYPERTENSION; STAGE RENAL-DISEASE; CYSTATIN-C; UNITED-STATES; RISK; MORTALITY; ASSOCIATION; PREVALENCE; CREATININE AB BACKGROUND Although hypertension contributes to kidney dysfunction in the general population, the contributions of elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) to kidney function decline in community-dwelling older adults are unknown. METHODS We used linear and logistic regression to examine the separate and combined associations of SBP, DBP, and PP at baseline with kidney function decline among 4,365 older adults in the Cardiovascular Health Study. We used cystatin C to estimate glomerular filtration rate on 3 occasions over 7 years of follow-up. We defined rapid decline >= 3 ml/min/year. RESULTS Average age was 72.2 and mean (standard deviation) SBP, DBP, and PP were 135 (21), 71 (11), and 65 (18) mm Hg, respectively. SBP and PP, rather than DBP, were most significantly associated with kidney function decline. In adjusted linear models, each 10-mm Hg increment in SBP and PP was associated with 0.13 ml/min/year (-0.19, -0.08, P < 0.001) and 0.15-ml/min/year faster decline (-0.21, -0.09, P < 0.001), respectively. Each 10-mm Hg increment in DBP was associated with a nonsignificant 0.10-ml/min/year faster decline (95% confidence interval, -0.20, 0.01). In adjusted logistic models, SBP had the strongest associations with rapid decline, with 14% increased hazard of rapid decline (95% confidence interval, 10% to 17%, P < 0.01) per 10 mm Hg. In models combining BP components, only SBP consistently had independent associations with rapid decline. CONCLUSIONS Our findings suggest that elevated BP, particularly SBP, contributes to declining kidney function in older adults. C1 [Rifkin, Dena E.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Rifkin, Dena E.] Univ Calif San Diego, Div Family & Prevent Med, San Diego, CA 92103 USA. [Rifkin, Dena E.] Vet Affairs Med Ctr, San Diego, CA 92161 USA. [Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Chonchol, Michel] Univ Colorado, Div Renal Dis & Hypertens, Denver, CO 80202 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Sch Med, Div Geriatr Med, Pittsburgh, PA 15261 USA. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP Rifkin, DE (reprint author), Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. EM drifkin@ucsd.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NHLBI [HHSN268201200036C, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295]; NIA [AG-023629, AG-15928, AG-20098, AG-027058] FX This work was supported by NHLBI contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grant HL080295, with additional contribution from NINDS. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also http://www.chs-nhlbi.org/pi.htm. NR 23 TC 9 Z9 11 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 2013 VL 26 IS 8 BP 1037 EP 1044 DI 10.1093/ajh/hpt067 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 182CO UT WOS:000321718300014 PM 23709568 ER PT J AU Miloslavsky, EM Specks, U Merkel, PA Seo, P Spiera, R Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Tchao, NK Viviano, L Ding, L Sejismundo, LP Mieras, K Ikle, D Jepson, B Mueller, M Brunetta, P Allen, NB Fervenza, FC Geetha, D Keogh, K Kissin, EY Monach, PA Peikert, T Stegeman, C Ytterberg, SR Stone, JH AF Miloslavsky, E. M. Specks, U. Merkel, P. A. Seo, P. Spiera, R. Langford, C. A. Hoffman, G. S. Kallenberg, C. G. M. St Clair, E. W. Tchao, N. K. Viviano, L. Ding, L. Sejismundo, L. P. Mieras, K. Ikle, D. Jepson, B. Mueller, M. Brunetta, P. Allen, N. B. Fervenza, F. C. Geetha, D. Keogh, K. Kissin, E. Y. Monach, P. A. Peikert, T. Stegeman, C. Ytterberg, S. R. Stone, J. H. CA Rituximab ANCA-Associated TI Clinical Outcomes of Remission Induction Therapy for Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANCA-ASSOCIATED VASCULITIS; DAILY ORAL CYCLOPHOSPHAMIDE; RANDOMIZED-TRIAL; FOLLOW-UP; RITUXIMAB; MAINTENANCE; AUTOANTIBODIES; GRANULOMATOSIS; AZATHIOPRINE; METHOTREXATE AB Objective. To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA). Methods. The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegener's Granulomatosis >0, prednisone treatment at any dosage, and other). Results. Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare. Conclusion. Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3- ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months. C1 [Miloslavsky, E. M.; Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Specks, U.; Mieras, K.; Fervenza, F. C.; Keogh, K.; Peikert, T.; Ytterberg, S. R.] Mayo Clin, Rochester, MN USA. [Merkel, P. A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Seo, P.; Sejismundo, L. P.; Geetha, D.] Johns Hopkins Univ, Baltimore, MD USA. [Spiera, R.] Hosp Special Surg, New York, NY 10021 USA. [Langford, C. A.; Hoffman, G. S.] Cleveland Clin, Cleveland, OH 44106 USA. [Kallenberg, C. G. M.; Stegeman, C.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Kallenberg, C. G. M.; Stegeman, C.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. W.; Allen, N. B.] Duke Univ, Med Ctr, Durham, NC USA. [Tchao, N. K.] Immune Tolerance Network, San Francisco, CA USA. [Viviano, L.; Ding, L.] NIAID, NIH, Bethesda, MD 20892 USA. [Ikle, D.; Jepson, B.] Rho, Chapel Hill, NC USA. [Mueller, M.] US FDA, Silver Spring, MD USA. [Brunetta, P.] Genentech Inc, San Francisco, CA 94080 USA. [Kissin, E. Y.; Monach, P. A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2C,55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org FU Immune Tolerance Network (NIH), an international clinical research consortium headquartered at the University of California San Francisco [N01-AI-15416, ITN021AI]; NIH (National Institute of Allergy and Infectious Diseases) [N01-AI-15416, ITN021AI]; Juvenile Diabetes Research Foundation; Genentech; Biogen Idec; NIH (Mayo Clinic: National Center for Research Resources Clinical and Translational Science) [RR-024150-01]; NIH (Johns Hopkins University: National Center for Research Resources Clinical and Translational Science) [RR-025005, K23-AR-052820, K24-AR-049185, RR-025771, M01-RR-00533, K24-AR-02224]; Arthritis Foundation FX The Rituximab in ANCA-Associated Vasculitis (RAVE) trial was performed with the support of the Immune Tolerance Network (NIH contract N01-AI-15416, protocol number ITN021AI), an international clinical research consortium headquartered at the University of California San Francisco and supported by the NIH (National Institute of Allergy and Infectious Diseases contract N01-AI-15416, protocol number ITN021AI) and the Juvenile Diabetes Research Foundation. Genentech and Biogen Idec provided the study medications and partial funding for the RAVE trial. At the Mayo Clinic, Johns Hopkins University, and Boston University School of Medicine, the RAVE trial was supported by the NIH (Mayo Clinic: National Center for Research Resources Clinical and Translational Science award RR-024150-01; Johns Hopkins University: National Center for Research Resources Clinical and Translational Science grant RR-025005 and career development awards K23-AR-052820 to Dr. Seo and K24-AR-049185 to Dr. Stone; Boston University: National Center for Research Resources Clinical and Translational Science award RR-025771, grant M01-RR-00533, and career development award K24-AR-02224 to Dr. Merkel). Dr. Miloslavsky's work was supported by Genentech (Clinical Immunology Fellowship). Dr. Monach's work was supported by the Arthritis Foundation (Arthritis Investigator Award). NR 21 TC 37 Z9 39 U1 0 U2 7 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 AUG PY 2013 VL 65 IS 9 BP 2441 EP 2449 DI 10.1002/art.38044 PG 9 WC Rheumatology SC Rheumatology GA 205YR UT WOS:000323481400027 PM 23754238 ER PT J AU Xie, G Roshandel, D Sherva, R Monach, PA Lu, EY Kung, T Carrington, K Zhang, SS Pulit, SL Ripke, S Carette, S Dellaripa, PF Edberg, JC Hoffman, GS Khalidi, N Langford, CA Mahr, AD St Clair, EW Seo, P Specks, U Spiera, RF Stone, JH Ytterberg, SR Raychaudhuri, S de Bakker, PIW Farrer, LA Amos, CI Merkel, PA Siminovitch, KA AF Xie, Gang Roshandel, Delnaz Sherva, Richard Monach, Paul A. Lu, Emily Yue Kung, Tabitha Carrington, Keisha Zhang, Steven S. Pulit, Sara L. Ripke, Stephan Carette, Simon Dellaripa, Paul F. Edberg, Jeffrey C. Hoffman, Gary S. Khalidi, Nader Langford, Carol A. Mahr, Alfred D. St Clair, E. William Seo, Philip Specks, Ulrich Spiera, Robert F. Stone, John H. Ytterberg, Steven R. Raychaudhuri, Soumya de Bakker, Paul I. W. Farrer, Lindsay A. Amos, Christopher I. Merkel, Peter A. Siminovitch, Katherine A. TI Association of Granulomatosis With Polyangiitis (Wegener's) With HLA-DPB1*04 and SEMA6A Gene Variants: Evidence Grom Genome-Wide Analysis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COPY NUMBER VARIATION; RHEUMATOID-ARTHRITIS; SYSTEMIC VASCULITIS; CHROMOSOME 6P21.3; INTERFERON-GAMMA; POLYMORPHISMS; RISK; SUSCEPTIBILITY; SEMAPHORINS; DISEASE AB Objective. To identify genetic determinants of granulomatosis with polyangiitis (Wegener's) (GPA). Methods. We carried out a genome-wide association study (GWAS) of 492 GPA cases and 1,506 healthy controls (white subjects of European descent), followed by replication analysis of the most strongly associated signals in an independent cohort of 528 GPA cases and 1,228 controls. Results. Genome-wide significant associations were identified in 32 single-nucleotide polymorphic (SNP) markers across the HLA region, the majority of which were located in the HLA-DPB1 and HLA-DPA1 genes encoding the class II major histocompatibility complex (MHC) DP chain 1 and DP chain 1 proteins, respectively. Peak association signals in these 2 genes, emanating from SNPs rs9277554 (for DP chain 1) and rs9277341 (DP chain 1) were strongly replicated in an independent cohort (in the combined analysis of the initial cohort and the replication cohort, P = 1.92 x 10(-50) and 2.18 x 10(-39), respectively). Imputation of classic HLA alleles and conditional analyses revealed that the SNP association signal was fully accounted for by the classic HLA-DPB1*04 allele. An independent single SNP, rs26595, near SEMA6A (the gene for semaphorin 6A) on chromosome 5, was also associated with GPA, reaching genome-wide significance in a combined analysis of the GWAS and replication cohorts (P = 2.09 x 10(-8)). Conclusion. We identified the SEMA6A and HLA-DP loci as significant contributors to risk for GPA, with the HLA-DPB1*04 allele almost completely accounting for the MHC association. These two associations confirm the critical role of immunogenetic factors in the development of GPA. C1 [Xie, Gang; Roshandel, Delnaz; Kung, Tabitha; Carrington, Keisha; Zhang, Steven S.; Carette, Simon] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Xie, Gang; Roshandel, Delnaz; Kung, Tabitha; Carrington, Keisha; Zhang, Steven S.; Carette, Simon; Siminovitch, Katherine A.] Univ Toronto, Toronto, ON, Canada. [Sherva, Richard; Monach, Paul A.; Farrer, Lindsay A.; Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Lu, Emily Yue; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pulit, Sara L.; Dellaripa, Paul F.; de Bakker, Paul I. W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pulit, Sara L.; de Bakker, Paul I. W.] Broad Inst, Boston, MA USA. [Pulit, Sara L.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Ripke, Stephan; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Edberg, Jeffrey C.] Univ Alabama Birmingham, Birmingham, AL USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Khalidi, Nader] McMaster Univ, Hamilton, ON, Canada. [Mahr, Alfred D.] Hop St Louis, Paris, France. [Mahr, Alfred D.] Univ Paris 07, Paris, France. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Specks, Ulrich; Ytterberg, Steven R.] Mayo Clin, Rochester, MN USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Broad Inst, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Partners Ctr Personalized Genet Med, Boston, MA USA. [Raychaudhuri, Soumya] Univ Manchester, Manchester, Lancs, England. [Amos, Christopher I.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Merkel, Peter A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Siminovitch, Katherine A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto Gen Res Inst, Toronto, ON M5G 1X5, Canada. RP Siminovitch, KA (reprint author), Mt Sinai Hosp, 600 Univ Ave,Room 778D, Toronto, ON M5G 1X5, Canada. EM ksimin@mshri.on.ca RI de Bakker, Paul/B-8730-2009; Siminovitch, Katherine/K-1475-2013; OI de Bakker, Paul/0000-0001-7735-7858; Farrer, Lindsay/0000-0001-5533-4225 FU Erna Baird Memorial Grant; Vasculitis Foundation Canada; Ontario Research Fund [RE-01-061]; Vasculitis Foundation; Vasculitis Clinical Research Consortium (NIH) [U54-RR-019497, U54-AR-47785, R01-AR-047799, R01-AG025259]; Arthritis Foundation; Societe Nationale Francaise de Medecine Interne; Netherlands Organization for Scientific Research; Mid-Career Development Award in Clinical Investigation (NIH-National Institute of Arthritis and Musculoskeletal and Skin Diseases) [K24-AR-02224]; Sanofi-Aventis; Roche; Genentech FX Supported by an Erna Baird Memorial Grant, the Vasculitis Foundation Canada, the Ontario Research Fund (RE-01-061), the Vasculitis Foundation, and the Vasculitis Clinical Research Consortium (NIH grants U54-RR-019497, U54-AR-47785, R01-AR-047799, and R01-AG025259). Dr. Monach's work was supported by the Arthritis Foundation. Dr. Mahr's work was supported in part by a grant from the Societe Nationale Francaise de Medecine Interne. Dr. de Bakker is recipient of a Vidi Award from The Netherlands Organization for Scientific Research. Dr. Merkel's work was supported by a Mid-Career Development Award in Clinical Investigation (NIH-National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K24-AR-02224). Dr. Siminovitch is a Tier 1 Canada Research Chair and the Sherman Family Chair in Genomic Medicine.; Dr. Hoffman has received consulting fees, speaking fees, and/or honoraria from Sanofi-Aventis, Roche, and Genentech (less than $10,000 each). NR 51 TC 31 Z9 32 U1 0 U2 7 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 AUG PY 2013 VL 65 IS 9 BP 2457 EP 2468 DI 10.1002/art.38036 PG 12 WC Rheumatology SC Rheumatology GA 205YR UT WOS:000323481400029 PM 23740775 ER PT J AU Hicks, CW Weinstein, M Wakamatsu, M Pulliam, S Savitt, L Bordeianou, L AF Hicks, C. W. Weinstein, M. Wakamatsu, M. Pulliam, S. Savitt, L. Bordeianou, L. TI Are rectoceles the cause or the result of obstructed defaecation syndrome? A prospective anorectal physiology study SO COLORECTAL DISEASE LA English DT Article DE Rectocele; obstructed defaecation syndrome; anorectal physiology ID TRANSANAL RECTAL RESECTION; LONG-TERM OUTCOMES; FECAL INCONTINENCE; PROLAPSE; INTUSSUSCEPTION; DEFECOGRAPHY; VOLUNTEERS; REPAIR; TRIAL AB Aim To determine the relationship between obstructed defaecation syndrome (ODS) and rectoceles. Method From December 2007 to November 2011, all female patients with ODS were prospectively evaluated with full interview, clinical examination and anorectal physiology testing. The characteristics of patients with and without rectoceles were compared, and logistic regression was utilized to identify factors predictive of patients having a rectocele beyond the introitus. Results Of 239 patients with ODS, 90 (mean age: 52.3 +/- 1.7 years) had a rectocele. Patients with rectoceles (R+) had a similar prevalence of incomplete emptying compared with patients with no rectocele (R-) (P >= 0.21), but only R+ patients reported splinting with defaecation (36.7% vs 0%; P < 0.0001). Anorectal manometry measurements, including mean resting pressure, maximum resting pressure and maximum squeeze pressure, were similar between groups (P >= 0.12). There were also no significant differences in rectal compliance (maximum tolerated volume) or rectal sensitivity (volume of first sensation) (P >= 0.65). R+ patients had greater difficulty expelling a 60 cm 3 balloon (70.1% R+ patients vs 57.5% R- patients; P = 0.05), but the prevalence of pelvic floor dyssynergia, as quantified by nonrelaxation on electromyography (EMG) testing, was similar to that of R- patients (P = 0.49). Logistic regression suggested that only difficulty with balloon expulsion was associated with higher odds of having a rectocele (OR = 3.00; P = 0.002), whereas mean resting pressure, EMG nonrelaxation and symptoms of incomplete emptying were not (P >= 0.12). Conclusion Rectoceles are not associated with an increased severity of ODS-type symptoms, anorectal abnormalities or pelvic floor dyssynergia in patients with ODS. This suggests that rectoceles may be the result, rather than the cause, of ODS. C1 [Hicks, C. W.; Savitt, L.; Bordeianou, L.] Massachusetts Gen Hosp, Dept Surg, Pelv Floor Disorders Serv, Boston, MA 02114 USA. [Hicks, C. W.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. [Weinstein, M.; Wakamatsu, M.; Pulliam, S.] Massachusetts Gen Hosp, Pelv Floor Disorders Serv, Dept Gynecol, Boston, MA 02114 USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 31 TC 12 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8910 J9 COLORECTAL DIS JI Colorectal Dis. PD AUG PY 2013 VL 15 IS 8 BP 993 EP 999 DI 10.1111/codi.12213 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 208KW UT WOS:000323678700023 PM 23527537 ER PT J AU Ho, JE Larson, MG Vasan, RS Ghorbani, A Cheng, S Rhee, EP Florez, JC Clish, CB Gerszten, RE Wang, TJ AF Ho, Jennifer E. Larson, Martin G. Vasan, Ramachandran S. Ghorbani, Anahita Cheng, Susan Rhee, Eugene P. Florez, Jose C. Clish, Clary B. Gerszten, Robert E. Wang, Thomas J. TI Metabolite Profiles During Oral Glucose Challenge SO DIABETES LA English DT Article ID BILE-ACID SYNTHESIS; INSULIN SENSITIVITY; TOLERANCE TEST; PLASMA; APPROPRIATE; RESISTANCE; INDUCTION; DIAGNOSIS; GLYCEMIA; DISEASE AB To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m(2)) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P <= 0.0005 for all). Amino acids, B-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in p-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state. Diabetes 62:2689-2698, 2013 C1 [Ho, Jennifer E.; Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; Wang, Thomas J.] Framingham Heart Study Natl Heart Lung & Blood In, Framingham, MA USA. [Ho, Jennifer E.; Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA. [Ho, Jennifer E.] Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Dept Med, Div Cardiol & Prevent Med, Boston, MA 02215 USA. [Ghorbani, Anahita; Gerszten, Robert E.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Rhee, Eugene P.; Gerszten, Robert E.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Rhee, Eugene P.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Rhee, Eugene P.; Clish, Clary B.; Gerszten, Robert E.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wang, TJ (reprint author), Framingham Heart Study Natl Heart Lung & Blood In, Framingham, MA USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health [NO1-HC-25195, R01-DK-HL-081572]; American Heart Association; Leducq Foundation; Ellison Foundation FX This work was supported by the National Institutes of Health (NO1-HC-25195 and R01-DK-HL-081572), the American Heart Association, the Leducq Foundation, and the Ellison Foundation. NR 38 TC 49 Z9 49 U1 1 U2 21 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2013 VL 62 IS 8 BP 2689 EP 2698 DI 10.2337/db12-0754 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 191RU UT WOS:000322431100014 PM 23382451 ER PT J AU Lessard, SJ Rivas, DA Alves-Wagner, AB Hirshman, MF Gallagher, IJ Constantin-Teodosiu, D Atkins, R Greenhaff, PL Qi, NR Gustafsson, T Fielding, RA Timmons, JA Britton, SL Koch, LG Goodyear, LJ AF Lessard, Sarah J. Rivas, Donato A. Alves-Wagner, Ana B. Hirshman, Michael F. Gallagher, Iain J. Constantin-Teodosiu, Dumitru Atkins, Ryan Greenhaff, Paul L. Qi, Nathan R. Gustafsson, Thomas Fielding, Roger A. Timmons, James A. Britton, Steven L. Koch, Lauren G. Goodyear, Laurie J. TI Resistance to Aerobic Exercise Training Causes Metabolic Dysfunction and Reveals Novel Exercise-Regulated Signaling Networks SO DIABETES LA English DT Article ID ALL-CAUSE MORTALITY; PROTEIN-KINASE-II; SKELETAL-MUSCLE; INSULIN-RESISTANCE; CARDIORESPIRATORY FITNESS; CARDIOVASCULAR-DISEASE; ARTIFICIAL SELECTION; GENE-EXPRESSION; CAPACITY; RISK AB Low aerobic exercise capacity is a risk factor for diabetes and a strong predictor of mortality, yet some individuals are "exercise-resistant" and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease risk, we used selective breeding for 15 generations to develop rat models of low and high aerobic response to training. Before exercise training, rats selected as low and high responders had similar exercise capacities. However, after 8 weeks of treadmill training, low responders failed to improve their exercise capacity, whereas high responders improved by 54%. Remarkably, low responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise-resistant phenotype segregates with disease risk. Low responders had impaired exercise-induced angiogenesis in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low responders. Low responders had increased stress/inflammatory signaling and altered transforming growth factor-8 signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system, we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease. Diabetes 62:2717-2727, 2013 C1 [Lessard, Sarah J.; Alves-Wagner, Ana B.; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Rivas, Donato A.; Fielding, Roger A.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Gallagher, Iain J.] Univ Stirling, Stirling FK9 4LA, Scotland. [Constantin-Teodosiu, Dumitru; Atkins, Ryan; Greenhaff, Paul L.] Univ Nottingham, Nottingham NG7 2RD, England. [Qi, Nathan R.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Gustafsson, Thomas; Timmons, James A.] Karolinska Inst, Huddinge, Sweden. [Timmons, James A.] Univ Loughborough, Loughborough, Leics, England. [Britton, Steven L.; Koch, Lauren G.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Alves Wagner, Ana Barbara/E-4556-2013; Timmons, James/J-4698-2014; OI Alves Wagner, Ana Barbara/0000-0002-3070-9454; Timmons, James/0000-0002-2255-1220; Gustafsson, Thomas/0000-0002-1559-4206; Rivas, Donato/0000-0002-4500-6233 FU National Institutes of Health [RO1AR042238, DK068626, RO1 DK077200]; Diabetes Research Center [5P30 DK 36836, DK089503]; Department of Anesthesiology, University of Michigan Medical School, Michigan Diabetes Research and Training Center [NIH5P60 DK20572-P/FS]; National Center for Research Resources [R24 RR017718]; Office of Research Infrastructure Programs/OD grant from the National Institutes of Health [ROD012098A]; FP7 EU grant; Wallenberg Foundation, Sweden; United States Department of Agriculture [58-1950-0-014]; Boston Claude D. Pepper Older Americans Independence Center [1P30AG031679]; American Physiological Society (Physiological Genomics); Canadian Diabetes Association FX This work was supported by National Institutes of Health grants RO1AR042238 and DK068626 (L.J.G.) and by Diabetes Research Center 5P30 DK 36836 (Joslin Diabetes Center) and DK089503 (University of Michigan). The HRT and LRT rat models are supported by the Department of Anesthesiology, University of Michigan Medical School, Michigan Diabetes Research and Training Center (NIH5P60 DK20572-P/FS; L.G.K.), National Center for Research Resources (R24 RR017718; L.G.K. and S.L.B.), and current support by Office of Research Infrastructure Programs/OD grant (ROD012098A) from the National Institutes of Health (L.G.K. and S.L.B.). This work also was supported by FP7 EU grant (J.A.T., T.G., and P.L.G.; METAPREDICT) and a grant from the Wallenberg Foundation, Sweden (T.G.).; S.L.B. was supported by National Institutes of Health grant RO1 DK077200. R.A.F. is supported by the United States Department of Agriculture under agreement 58-1950-0-014. D.A.R. is supported by the Boston Claude D. Pepper Older Americans Independence Center (1P30AG031679). S.J.L. is supported by postdoctoral fellowships from the American Physiological Society (Physiological Genomics) and the Canadian Diabetes Association. NR 58 TC 18 Z9 18 U1 1 U2 24 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2013 VL 62 IS 8 BP 2717 EP 2727 DI 10.2337/db13-0062 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 191RU UT WOS:000322431100017 PM 23610057 ER PT J AU Richardson, P Lokhorst, H Palumbo, A Nahi, H Laubach, J Gimsing, P Lisby, S Cakana, A Brun, NC Plesner, T AF Richardson, P. Lokhorst, H. Palumbo, A. Nahi, H. Laubach, J. Gimsing, P. Lisby, S. Cakana, A. Brun, N. Constantin Plesner, T. TI DARATUMUMAB Anti-CD38 Monoclonal Antibody, Treatment of Multiple Myeloma SO DRUGS OF THE FUTURE LA English DT Article DE Transmembrane glycoprotein; Immunotherapy; Multiple myeloma; Daratumumab ID IMMUNOMODULATORY DRUGS IMIDS; HUMAN CD38; PROTEASOME INHIBITORS; TREATMENT STRATEGIES; THERAPY; IMMUNOTHERAPY; SURVIVAL; LENALIDOMIDE; COMBINATION; BORTEZOMIB AB CD38 is a type II transmembrane glycoprotein that is highly expressed in hematological malignancies, including multiple myeloma (MM). Therefore, CD38 is a promising target for antibody immunotherapy. Daratumumab is a human monoclonal antibody with broad-spectrum killing activity. In vitro, daratumumab induces anti-MM effects via complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. Synergistic activity was demonstrated in vitro in combination with standard MM therapies, including bortezomib and lenalidomide. Protective bone marrow stromal cells did not influence daratumumab-induced CDC and ADCC, suggesting that daratumumab may have activity in the bone marrow microenvironment in vivo. Indeed, significant daratumumab-mediated tumor growth inhibition was shown in MM mouse xenograft models. A phase I/II clinical study is ongoing in patients with relapsed/refractory MM. This review discusses the preclinical pharmacology, pharmacokinetics and preliminary clinical efficacy of daratumumab and its potential in MM therapy. C1 [Richardson, P.; Laubach, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lokhorst, H.] Univ Med Ctr, Utrecht, Netherlands. [Palumbo, A.] Univ Turin, Turin, Italy. [Nahi, H.] Karolinska Inst, Stockholm, Sweden. [Gimsing, P.] Copenhagen Univ Hosp, Copenhagen, Denmark. [Lisby, S.; Brun, N. Constantin] Genmab AS, Copenhagen, Denmark. [Cakana, A.] Janssen Res & Dev, High Wycombe, Bucks, England. [Plesner, T.] Vejle Hosp, Vejle, Denmark. RP Richardson, P (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu OI nahi, hareth/0000-0003-4711-5094 FU Genmab FX The authors gratefully acknowledge the writing support of Steve Hill, of FireKite, which was funded by Genmab, in the preparation of this manuscript. The authors also gratefully acknowledge the administrative assistance of Michelle Maglio and Vibeke Leth. NR 69 TC 0 Z9 0 U1 0 U2 9 PU PROUS SCIENCE, SAU-THOMSON REUTERS PI BARCELONA PA 398 PROVENCA, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD AUG PY 2013 VL 38 IS 8 BP 545 EP 554 DI 10.1358/dof.2013.38.8.2025424 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 208KT UT WOS:000323678300002 ER PT J AU Perkins, PS Slane, JD Klump, KL AF Perkins, Patrick Scott Slane, Jennifer D. Klump, Kelly L. TI Personality clusters and family relationships in women with disordered eating symptoms SO EATING BEHAVIORS LA English DT Article DE Personality clusters; Family relationships; Disordered eating ID PARENTAL-BONDING INSTRUMENT; BEHAVIORAL RISK-FACTORS; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; STRUCTURAL-ANALYSIS; ADOLESCENT GIRLS; SOCIAL-ADJUSTMENT; SELF-REPORT; DSM-IV; SUBTYPES AB Personality clusters in women with eating disorders predict important clinical variables (e.g., social functioning) better than eating disorder diagnoses. However, it is unknown whether these findings generalize to samples with subclinical pathology. Further, little is known about associations between personality clusters and family relationships. This study sought to address these limitations by replicating personality clusters in a college sample of women with disordered eating symptoms Based on reported symptoms, women were divided into a restricting, binging and purging, or control (i.e., symptom free) group. Participants completed measures of personality, social functioning, and family relationships. Cluster analyses suggested three personality groups (i.e., Adaptive, Rigid, Dysregulated) which corresponded to those identified previously in clinical samples. Personality clusters, and not disordered eating groups, significantly predicted social functioning, and these clusters were differentially associated with family conflict type. Meaningful personality clusters are present in subclinical populations and have clinical utility in predicting social functioning and family relationships. Published by Elsevier Ltd. C1 [Perkins, Patrick Scott] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Slane, Jennifer D.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Slane, Jennifer D.] Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA USA. [Klump, Kelly L.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. RP Slane, JD (reprint author), 7180 Highland Dr,Suite 201N,Bldg 4,2nd Floor, Pittsburgh, PA 15206 USA. EM jennifer.slane@va.gov NR 71 TC 4 Z9 5 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 EI 1873-7358 J9 EAT BEHAV JI Eat. Behav. PD AUG PY 2013 VL 14 IS 3 BP 299 EP 308 DI 10.1016/j.eatbeh.2013.05.007 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 207GK UT WOS:000323586700012 PM 23910771 ER PT J AU Popa, SM Moriyama, RM Caligioni, CS Yang, JJ Cho, CM Concepcion, TL Oakley, AE Lee, IH Sanz, E Amieux, PS Caraty, A Palmiter, RD Navarro, VM Chan, YM Seminara, SB Clifton, DK Steiner, RA AF Popa, Simina M. Moriyama, Ryutaro M. Caligioni, Claudia S. Yang, Jasmine J. Cho, Caroline M. Concepcion, Tessa L. Oakley, Amy E. Lee, In Hae Sanz, Elisenda Amieux, Paul S. Caraty, Alain Palmiter, Richard D. Navarro, Victor M. Chan, Yee-Ming Seminara, Stephanie B. Clifton, Donald K. Steiner, Robert A. TI Redundancy in Kiss1 Expression Safeguards Reproduction in the Mouse SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE SURGE; ARCUATE NUCLEUS; NEUROKININ B; HYPOTHALAMIC NOREPINEPHRINE; GONADOTROPIN-SECRETION; MESSENGER-RNA; BRAIN GRAFTS; BODY-WEIGHT; FEMALE RATS; NEURONS AB Kisspeptin (Kiss1) signaling to GnRH neurons is widely acknowledged to be a prerequisite for puberty and reproduction. Animals lacking functional genes for either kisspeptin or its receptor exhibit low gonadotropin secretion and infertility. Paradoxically, a recent study reported that genetic ablation of nearly all Kiss1-expressing neurons (Kiss1 neurons) does not impair reproduction, arguing that neither Kiss1 neurons nor their products are essential for sexual maturation. We posited that only minute quantities of kisspeptin are sufficient to support reproduction. If this were the case, animals having dramatically reduced Kiss1 expression might retain fertility, testifying to the redundancy of Kiss1 neurons and their products. To test this hypothesis and to determine whether males and females differ in the required amount of kisspeptin needed for reproduction, we used a mouse (Kiss1-CreGFP) that has a severe reduction in Kiss1 expression. Mice that are heterozygous and homozygous for this allele (Kiss1(Cre/+) and Kiss1(Cre/Cre)) have similar to 50% and 95% reductions in Kiss1 transcript, respectively. We found that although male Kiss1(Cre/Cre) mice sire normal-sized litters, female Kiss1(Cre/Cre) mice exhibit significantly impaired fertility and ovulation. These observations suggest that males require only 5% of normal Kiss1 expression to be reproductively competent, whereas females require higher levels for reproductive success. C1 [Popa, Simina M.] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA. [Popa, Simina M.; Moriyama, Ryutaro M.; Cho, Caroline M.; Concepcion, Tessa L.; Lee, In Hae; Clifton, Donald K.; Steiner, Robert A.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Oakley, Amy E.; Steiner, Robert A.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Sanz, Elisenda; Amieux, Paul S.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Palmiter, Richard D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Palmiter, Richard D.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Moriyama, Ryutaro M.] Kinki Univ, Dept Life Sci, Higashiosaka, Osaka 5778502, Japan. [Caligioni, Claudia S.; Yang, Jasmine J.; Chan, Yee-Ming; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [Caligioni, Claudia S.; Yang, Jasmine J.; Chan, Yee-Ming; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Navarro, Victor M.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Caraty, Alain] Univ Tours, Haras Nationaux, CNRS, INRA,UMR 6175, F-37380 Nouzilly, France. RP Steiner, RA (reprint author), Univ Washington, Dept Physiol & Biophys, Box 357290, Seattle, WA 98195 USA. EM steiner@uw.edu RI Sanz, Elisenda/I-2765-2015 OI Sanz, Elisenda/0000-0002-7932-8556 FU National Institutes of Health (NIH) [2 R01 HD049651, U54 HD028138]; JSPS KAKENHI [23780282]; Developmental Biology Training Grant at the University of Washington [NIH T32HD007183]; Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH (Specialized Cooperative Centers Program in Reproduction and Infertility Research) [U54-HD28934] FX This research was supported by National Institutes of Health (NIH) Grant 2 R01 HD049651 (to R.A.S.), U54 HD028138 (to S.B.S.), and JSPS KAKENHI 23780282 (to R.M.M.). We acknowledge support from the Developmental Biology Training Grant at the University of Washington (NIH T32HD007183). We are grateful to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core (supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH (Specialized Cooperative Centers Program in Reproduction and Infertility Research) Grant U54-HD28934) NR 39 TC 25 Z9 25 U1 0 U2 13 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 AUG PY 2013 VL 154 IS 8 BP 2784 EP 2794 DI 10.1210/en.2013-1222 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 186SC UT WOS:000322063900024 PM 23736293 ER PT J AU Ananthakrishnan, AN AF Ananthakrishnan, Ashwin N. TI Personalizing therapy for inflammatory bowel diseases SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE biologics; Crohn's disease; genetics; serology; ulcerative colitis ID POPULATION-BASED COHORT; POSTOPERATIVE CROHNS-DISEASE; POUCH-ANAL ANASTOMOSIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; ULCERATIVE-COLITIS PATIENTS; NATURAL-HISTORY; SEROLOGICAL MARKERS; INFLIXIMAB THERAPY; CLINICAL-COURSE; HOSPITALIZATION RATES AB Inflammatory bowel diseases (IBDs; e.g., Crohn's disease [CD] and ulcerative colitis [UC]) are chronic immunologically mediated diseases characterized by frequent relapses, often requiring hospitalization and surgery. There is substantial heterogeneity in the progressive natural history of disease with cumulative accrual of bowel damage and impairment of functioning. Recent advances in therapeutics have significantly improved our ability to achieve disease remission; yet therapies remain expensive and are associated with significant side effects precluding widespread use in all patients with IBD. Consequently, algorithms for the management of patients with IBD require a personalized approach incorporating an individual's projected likely natural history, the probability of response to a specific therapeutic agent and an informed approach to management of loss of response to current therapies. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU US National Institutes of Health [K23 DK097142] FX AN Ananthakrishnan is supported by funding from the US National Institutes of Health (K23 DK097142). The author has served on the scientific advisory boards for Prometheus, Inc. and Janssen, Inc. 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 113 TC 5 Z9 5 U1 0 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 EI 1747-4132 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD AUG PY 2013 VL 7 IS 6 BP 549 EP 558 DI 10.1586/17474124.2013.824693 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208CE UT WOS:000323652800010 PM 23985004 ER PT J AU Ring, D AF Ring, David TI Symptoms and Disability After Major Peripheral Nerve Injury SO HAND CLINICS LA English DT Article DE Peripheral nerve injury; Coping strategy; Cognitive behavioral therapy; symptoms; Disability ID QUALITY-OF-LIFE; COLD INTOLERANCE; PATIENT SATISFACTION; HAND INJURIES; PAIN; SENSITIVITY; DEPRESSION; PREDICTORS; TRANSFERS AB Laceration and irrecoverable stretch, crush, or avulsion of a major peripheral nerve in the upper extremity causes substantial impairment in an adult patient. Hand care professionals who treat these patients encounter a wide range of coping strategies leading to varied courses of recovery and strikingly different final outcomes. There is evidence that the cognitive, emotional, and behavioral aspects of recovery (not to mention the circumstantial aspects such as worker compensation and litigation) are as important as the physical aspects. Awareness of the factors that facilitate or hinder these aspects of recovery might improve the quality and effectiveness of our care. C1 Massachusetts Gen Hosp, MGH Hand Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, MGH Hand Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 1 Z9 3 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 0749-0712 J9 HAND CLIN JI Hand Clin. PD AUG PY 2013 VL 29 IS 3 BP 421 EP + DI 10.1016/j.hcl.2013.04.008 PG 6 WC Orthopedics SC Orthopedics GA 207TR UT WOS:000323627800011 PM 23895722 ER PT J AU Fisher, DE Geller, AC AF Fisher, David E. Geller, Alan C. TI Disproportionate Burden of Melanoma Mortality in Young US Men The Possible Role of Biology and Behavior SO JAMA DERMATOLOGY LA English DT Editorial Material ID UNITED-STATES C1 [Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Geller, Alan C.] Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Bartlett Hall,55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org NR 5 TC 7 Z9 7 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD AUG PY 2013 VL 149 IS 8 BP 903 EP 904 DI 10.1001/jamadermatol.2013.4437 PG 2 WC Dermatology SC Dermatology GA 208ZH UT WOS:000323721400003 PM 23804228 ER PT J AU Strazzula, L Nigwekar, SU Steele, D Tsiaras, W Sise, M Bis, S Smith, GP Kroshinsky, D AF Strazzula, Lauren Nigwekar, Sagar U. Steele, David Tsiaras, William Sise, Meghan Bis, Sabina Smith, Gideon P. Kroshinsky, Daniela TI Intralesional Sodium Thiosulfate for the Treatment of Calciphylaxis SO JAMA DERMATOLOGY LA English DT Article ID CALCIFIC UREMIC ARTERIOLOPATHY; THERAPY; PATIENT AB IMPORTANCE Calciphylaxis is a potentially fatal disorder of abnormal calcium deposition. Patients commonly present with painful retiform to stellate purpuric lesions that often undergo ulceration and necrosis, increasing the risk of infection and life-threatening sepsis. Treatment is multifaceted, and improved outcomes have been demonstrated with intravenous sodium thiosulfate; however, the use of this medication can be limited by its adverse effects. The use of topical sodium thiosulfate has been successfully reported for superficial calcium deposits in the skin from other processes. Therefore, we hypothesized that intralesional (IL) sodium thiosulfate may be an effective treatment for the deeper lesions of cutaneous calciphylaxis. We provide a retrospective case review of 4 patients with calciphylaxis who were treated with IL sodium thiosulfate. OBSERVATIONS Four patients with biopsy-proven cutaneous calciphylaxis were treated with IL sodium thiosulfate (250 mg/mL) in areas of clinically active disease. The patients tolerated the medication well, with only transient localized discomfort during injection. All 4 patients had complete healing of their ulcers and remission of disease. CONCLUSIONS AND RELEVANCE Intralesional sodium thiosulfate may be an effective and well-tolerated treatment for localized calciphylaxis. This novel approach requires further research and investigation. C1 [Strazzula, Lauren; Tsiaras, William; Bis, Sabina; Smith, Gideon P.; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Nigwekar, Sagar U.; Steele, David] Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. [Sise, Meghan] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St, Boston, MA 02114 USA. EM dkroshinsky@partners.org OI Tsiaras, William/0000-0002-4080-4762 NR 14 TC 19 Z9 20 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6068 J9 JAMA DERMATOL JI JAMA Dermatol. PD AUG PY 2013 VL 149 IS 8 BP 946 EP 949 DI 10.1001/jamadermatol.2013.4565 PG 4 WC Dermatology SC Dermatology GA 208ZH UT WOS:000323721400012 PM 23760631 ER PT J AU Blacker, D AF Blacker, Deborah TI Food for Thought SO JAMA NEUROLOGY LA English DT Editorial Material ID CARDIOVASCULAR-DISEASE; ALZHEIMERS-DISEASE; DEMENTIA C1 [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gerontol Res Unit,Dept Psychiat, Boston, MA USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Blacker, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, 149 13th St, Charlestown, MA 02129 USA. EM blacker@psych.mgh.harvard.edu FU NIA NIH HHS [P50 AG005134-28, U01 AG032984-03, 1P01AG036694]; NINDS NIH HHS [R01 NS062028-04] NR 10 TC 0 Z9 0 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2013 VL 70 IS 8 BP 967 EP 968 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 206ZO UT WOS:000323565900002 PM 23779081 ER PT J AU Hanson, AJ Bayer-Carter, JL Green, PS Montine, TJ Wilkinson, CW Baker, LD Watson, S Bonner, LM Callaghan, M Leverenz, JB Tsai, E Postupna, N Zhang, J Lampe, J Craft, S AF Hanson, Angela J. Bayer-Carter, Jennifer L. Green, Pattie S. Montine, Thomas J. Wilkinson, Charles W. Baker, Laura D. Watson, Stennis Bonner, Laura M. Callaghan, Maureen Leverenz, James B. Tsai, Elaine Postupna, Nadia Zhang, Jing Lampe, Johanna Craft, Suzanne TI Effect of Apolipoprotein E Genotype and Diet on Apolipoprotein E Lipidation and Amyloid Peptides Randomized Clinical Trial SO JAMA NEUROLOGY LA English DT Article ID A-BETA OLIGOMERS; SPORADIC ALZHEIMERS-DISEASE; MILD COGNITIVE IMPAIRMENT; HIGH-DENSITY-LIPOPROTEIN; TRANSGENIC MOUSE MODEL; CEREBROSPINAL-FLUID; INSULIN-RESISTANCE; BRAIN INSULIN; DIABETES-MELLITUS; PRECURSOR PROTEIN AB IMPORTANCE Sporadic Alzheimer disease (AD) is caused in part by decreased clearance of the beta-amyloid (A beta) peptide breakdown products. Lipid-depleted (LD) apolipoproteins are less effective at binding and clearing A beta, and LD A beta peptides are more toxic to neurons. However, not much is known about the lipid states of these proteins in human cerebrospinal fluid. OBJECTIVE To characterize the lipidation states of A beta peptides and apolipoprotein E in the cerebrospinal fluid in adults with respect to cognitive diagnosis and APOE epsilon 4 allele carrier status and after a dietary intervention. DESIGN Randomized clinical trial. SETTING Veterans Affairs Medical Center clinical research unit. PARTICIPANTS Twenty older adults with normal cognition (mean [SD] age, 69 [7] years) and 27 with amnestic mild cognitive impairment (67 [6] years). INTERVENTIONS Randomization to a diet high in saturated fat content and with a high glycemic index (High diet; 45% of energy from fat [>25% saturated fat], 35%-40% from carbohydrates with a mean glycemic index >70, and 15%-20% from protein) or a diet low in saturated fat content and with a low glycemic index (Low diet; 25% of energy from fat [<7% saturated fat], 55%-60% from carbohydrates with a mean glycemic index <55, and 15%-20% from protein). MAIN OUTCOMES AND MEASURES Lipid-depleted A beta 42 and A beta 40 and apolipoprotein E in cerebrospinal fluid. RESULTS Baseline levels of LD A beta were greater for adults with mild cognitive impairment compared with adults with normal cognition (LD A beta 42, P =.05; LD A beta 40, P = .01). These findings were magnified in adults with mild cognitive impairment and the epsilon 4 allele, who had higher LD apolipoprotein E levels irrespective of cognitive diagnosis (P < .001). The Low diet tended to decrease LD A beta levels, whereas the High diet increased these fractions (LD A beta 42, P = .01; LD A beta 40, P = .15). Changes in LD A beta levels with the Low diet negatively correlated with changes in cerebrospinal fluid levels of insulin (LD A beta 42 and insulin, r = -0.68 [P = .01]; LD A beta 40 and insulin, r = -0.78 [P = .002]). CONCLUSIONS AND RELEVANCE The lipidation states of apolipoproteins and A beta peptides in the brain differ depending on APOE genotype and cognitive diagnosis. Concentrations can be modulated by diet. These findings may provide insight into the mechanisms through which apolipoprotein E4 and unhealthy diets impart risk for developing AD. C1 [Hanson, Angela J.; Bayer-Carter, Jennifer L.; Green, Pattie S.; Wilkinson, Charles W.; Baker, Laura D.; Watson, Stennis; Bonner, Laura M.; Callaghan, Maureen; Craft, Suzanne] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Leverenz, James B.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr,Dept Neurol, Seattle, WA USA. [Hanson, Angela J.; Green, Pattie S.; Tsai, Elaine] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Bayer-Carter, Jennifer L.; Wilkinson, Charles W.; Baker, Laura D.; Watson, Stennis; Bonner, Laura M.; Postupna, Nadia; Zhang, Jing; Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.; Lampe, Johanna] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Craft, S (reprint author), Wake Forest Univ, Sch Med, Dept Internal Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM suzcraft@wakehealth.edu FU Hartford Center of Excellence scholarship; National Institute on Aging [R37-AG-10880, P50 AG-05136]; Nancy and Buster Alvord Endowment; Department of Veterans Affairs; [T32 AG-000258-13] FX This study was supported by grant T32 AG-000258-13 and a Hartford Center of Excellence scholarship (Dr Hanson); by grants R37-AG-10880 (Dr Craft) and P50 AG-05136 (Dr Montine) from the National Institute on Aging; by the Nancy and Buster Alvord Endowment; and by the Department of Veterans Affairs. NR 67 TC 22 Z9 23 U1 0 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2013 VL 70 IS 8 BP 972 EP 980 DI 10.1001/jamaneurol.2013.396 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 206ZO UT WOS:000323565900004 PM 23779114 ER PT J AU Falcone, GJ Biffi, A Brouwers, HB Anderson, CD Battey, TWK Ayres, AM Vashkevich, A Schwab, K Rost, NS Goldstein, JN Viswanathan, A Greenberg, SM Rosand, J AF Falcone, Guido J. Biffi, Alessandro Brouwers, H. Bart Anderson, Christopher D. Battey, Thomas W. K. Ayres, Alison M. Vashkevich, Anastasia Schwab, Kristin Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan TI Predictors of Hematoma Volume in Deep and Lobar Supratentorial Intracerebral Hemorrhage SO JAMA NEUROLOGY LA English DT Article ID BLOOD-PRESSURE REDUCTION; ACTIVATED FACTOR-VII; EXPANSION; MORTALITY; INTERACT; WARFARIN; GROWTH; TRIAL AB IMPORTANCE Hematoma volume is the strongest predictor of outcome in intracerebral hemorrhage (ICH). Despite known differences in the underlying biology between deep and lobar ICHs, limited data are available on location specificity of factors reported to affect hematoma volume. OBJECTIVE To evaluate whether determinants of ICH volume differ by topography, we sought to estimate location-specific effects for potential predictors of this radiological outcome. DESIGN Prospective cohort study. SETTING Academic medical center. PARTICIPANTS A total of 744 supratentorial primary ICH patients (388 deep and 356 lobar) aged older than 18 years admitted between January 1, 2000, and December 31, 2010. MAIN OUTCOMES AND MEASURES Intracerebral hemorrhage volume measured from the computed tomography scan obtained on presentation to the emergency department. Linear regression analysis, stratified by ICH location, was implemented to identify determinants of log-transformed ICH volume. RESULTS Median ICH volume was larger in lobar hemorrhages (39 mL; interquartile range, 16-75 mL) than in deep hemorrhages (13 mL; interquartile range, 5-40 mL; P < .001). In multivariable linear regression, independent predictors of deep ICH volume were intensity of anticoagulation (beta = 0.32; standard error [SE] = 0.08; P < .001; test for trend across 4 categories of the international normalized ratio), history of coronary artery disease (beta = 0.33; SE = 0.17; P =.05), male sex (beta = 0.28; SE = 0.14; P =.05), and age (beta = -0.02; SE = 0.01; P = .001). Independent predictors of lobar ICH volume were intensity of anticoagulation (beta = 0.14; SE = 0.06; P = .02) and antiplatelet treatment (beta = 0.27; SE = 0.13; P = .03). CONCLUSIONS AND RELEVANCE Predictors of hematoma volume only partially overlap between deep and lobar ICHs. These findings suggest that the mechanisms that determine the extent of bleeding differ for deep and lobar ICHs. Further studies are needed to characterize the specific biological pathways that underlie the observed associations. C1 [Falcone, Guido J.; Biffi, Alessandro; Brouwers, H. Bart; Anderson, Christopher D.; Battey, Thomas W. K.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Brouwers, H. Bart; Anderson, Christopher D.; Battey, Thomas W. K.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Brouwers, H. Bart; Anderson, Christopher D.; Battey, Thomas W. K.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Brouwers, H. Bart; Anderson, Christopher D.; Battey, Thomas W. K.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Falcone, Guido J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Ayres, Alison/0000-0002-5492-1695; Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01NS073344, R01NS059727, 5K23NS059774]; American Heart Association [0755984T] FX This study was supported by grants R01NS073344, R01NS059727, and 5K23NS059774 from the National Institutes of Health/National Institute of Neurological Disorders and Stroke and grant 0755984T from the American Heart Association. NR 21 TC 20 Z9 21 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2013 VL 70 IS 8 BP 988 EP 994 DI 10.1001/jamaneurol.2013.98 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 206ZO UT WOS:000323565900006 PM 23733000 ER PT J AU Diercks, GR Ojha, S Infusino, S Maurer, R Hartnick, CJ AF Diercks, Gillian R. Ojha, Shilpa Infusino, Scott Maurer, Rie Hartnick, Christopher J. TI Consistency of Voice Frequency and Perturbation Measures in Children Using Cepstral Analyses A Movement Toward Increased Recording Stability SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CONTINUOUS SPEECH; DYSPHONIA SEVERITY; ACOUSTIC INDEX; DISORDERS; DATABASE AB IMPORTANCE Few studies have evaluated the pediatric voice objectively using acoustic measurements. Furthermore, consistency of these measurements across time, particularly for continuous speech, has not been evaluated. OBJECTIVES (1) To evaluate normal pediatric voice frequency and perturbation using both time-based and frequency-based acoustic measurements, and (2) to determine if continuous speech samples facilitate increased recording stability. DESIGN Prospective, longitudinal study. SETTING Pediatric otolaryngology practice within a tertiary hospital. PARTICIPANTS Forty-three children, ages 4 to 17 years. INTERVENTION OR EXPOSURE Sustained vowel utterances and continuous speech samples, which included 4 Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) sentences and the first sentence of the "rainbow passage" ("A rainbow is a division of white light into many beautiful colors that takes the shape of a long round arch, with its path high above and its 2 ends apparently beyond the horizon") were obtained at 2 time points MAIN OUTCOME AND MEASURE Intraclass correlation coefficients (ICCs) were calculated to assess reliability between speech samples. RESULTS Fundamental frequency of sustained vowel utterances had excellent reliability (ICC >= 0.94). Time-based analyses of perturbation in sustained vowel utterances demonstrated poor reliability (ICC < 0.40), while frequency-based analyses of perturbation for these utterances demonstrated good to excellent reliability (ICC > 0.40). Fundamental frequency of continuous speech sample had excellent reliability (ICC > 0.94). Frequency-based analyses of continuous speech samples demonstrated excellent reliability (ICC > 0.75) for all but 1 variable, which demonstrated good reliability (cepstral-spectral index of dysphonia of the all voiced sample; ICC = 0.72). CONCLUSIONS AND RELEVANCE Sustained vowel utterance and continuous speech samples provide consistent measures of fundamental frequency. Frequency-based analysis of sustained vowel recordings improves the reliability of perturbation measures. Continuous speech recordings can be obtained in children and demonstrate good to excellent reliability across recordings. This suggests that frequency-based analysis of continuous speech may be more representative of a child's voice and therefore may be of use in the study both of the developmental changes of the pediatric voice as well as the study of vocal changes pretreatment and posttreatment in children with voice disorders. C1 [Diercks, Gillian R.; Ojha, Shilpa; Infusino, Scott; Hartnick, Christopher J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Maurer, Rie] Brigham & Womens Hosp, Ctr Clin Investigat, Boston, MA 02115 USA. [Maurer, Rie] Harvard Clin & Translat Sci Ctr, Harvard Catalyst, Boston, MA USA. RP Diercks, GR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM Gillian_Diercks@meei.harvard.edu NR 21 TC 3 Z9 3 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD AUG PY 2013 VL 139 IS 8 BP 811 EP 816 DI 10.1001/jamaoto.2013.3926 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 206TM UT WOS:000323545800009 PM 23949356 ER PT J AU Chambers, KJ Sedaghat, AR Roberts, DS Caradonna, DS AF Chambers, Kyle J. Sedaghat, Ahmad R. Roberts, Daniel S. Caradonna, David S. TI Nasal Obstruction and Anosmia Respiratory epithelial adenomatoid hamartoma (REAH) SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID OLFACTORY CLEFTS C1 [Chambers, Kyle J.; Sedaghat, Ahmad R.; Roberts, Daniel S.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Chambers, Kyle J.; Sedaghat, Ahmad R.; Roberts, Daniel S.; Caradonna, David S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Caradonna, David S.] Beth Israel Deaconess Med Ctr, Div Otolaryngol Head & Neck Surg, Boston, MA 02215 USA. RP Chambers, KJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kyle_chambers@meei.harvard.edu NR 8 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6181 J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD AUG PY 2013 VL 139 IS 8 BP 851 EP 852 DI 10.1001/jamaoto.2013.3823 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 206TM UT WOS:000323545800017 PM 23949364 ER PT J AU Taveras, EM Gillman, MW Kleinman, KP Rich-Edwards, JW Rifas-Shiman, SL AF Taveras, Elsie M. Gillman, Matthew W. Kleinman, Ken P. Rich-Edwards, Janet W. Rifas-Shiman, Sheryl L. TI Reducing Racial/Ethnic Disparities in Childhood Obesity The Role of Early Life Risk Factors SO JAMA PEDIATRICS LA English DT Article ID BODY-MASS INDEX; INCOME PRESCHOOL-CHILDREN; US CHILDREN; BLOOD-PRESSURE; WEIGHT-GAIN; SOCIOECONOMIC-STATUS; UNITED-STATES; OVERWEIGHT; ADOLESCENTS; PREVALENCE AB IMPORTANCE Many early life risk factors for childhood obesity are more prevalent among blacks and Hispanics than among whites and may explain the higher prevalence of obesity among racial/ethnic minority children. OBJECTIVE To examine the extent to which racial/ethnic disparities in adiposity and overweight are explained by differences in risk factors during pregnancy (gestational diabetes and depression), infancy (rapid infant weight gain, feeding other than exclusive breastfeeding, and early introduction of solid foods), and early childhood (sleeping <12 h/d, presence of a television set in the room where the child sleeps, and any intake of sugar-sweetened beverages or fast food). DESIGN Prospective prebirth cohort study. SETTING Multisite group practice in Massachusetts. PARTICIPANTS Participants included 1116 mother-child pairs (63% white, 17% black, and 4% Hispanic) EXPOSURE Mother's report of child's race/ethnicity. MAIN OUTCOMES AND MEASURES Age- and sex-specific body mass index (BMI) z score, total fat mass index from dual-energy x-ray absorptiometry, and overweight or obesity, defined as a BMI in the 85th percentile or higher at age 7 years. RESULTS Black (0.48 U [95% CI, 0.31 to 0.64]) and Hispanic (0.43 [0.12 to 0.74]) children had higher BMI z scores, as well as higher total fat mass index and overweight/obesity prevalence, than white children. After adjustment for socioeconomic confounders and parental BMI, differences in BMI z score were attenuated for black and Hispanic children (0.22 U [0.05 to 0.40] and 0.22 U [-0.08 to 0.52], respectively). Adjustment for pregnancy risk factors did not substantially change these estimates. However, after further adjustment for infancy and childhood risk factors, we observed only minimal differences in BMI z scores between whites, blacks (0.07 U [-0.11 to 0.26]), and Hispanics (0.04 U [-0.27 to 0.35]). We observed similar attenuation of racial/ethnic differences in adiposity and prevalence of overweight or obesity. CONCLUSIONS AND RELEVANCE Racial/ethnic disparities in childhood adiposity and obesity are determined by factors operating in infancy and early childhood. Efforts to reduce obesity disparities should focus on preventing early life risk factors. C1 [Taveras, Elsie M.; Gillman, Matthew W.; Kleinman, Ken P.; Rifas-Shiman, Sheryl L.] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA USA. [Taveras, Elsie M.; Gillman, Matthew W.; Kleinman, Ken P.; Rifas-Shiman, Sheryl L.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Taveras, Elsie M.] Boston Childrens Hosp, Div Gen Pediat, Boston, MA USA. [Rich-Edwards, Janet W.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. RP Taveras, EM (reprint author), MassGen Hosp Children, Div Gen Pediat, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM etaveras@partners.org FU National Institute on Minority Health and Health Disparities [MD 003963] FX This study was supported by grant MD 003963 from the National Institute on Minority Health and Health Disparities. NR 53 TC 48 Z9 50 U1 7 U2 59 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 J9 JAMA PEDIATR JI JAMA Pediatr. PD AUG PY 2013 VL 167 IS 8 BP 731 EP 738 DI 10.1001/jamapediatrics.2013.85 PG 8 WC Pediatrics SC Pediatrics GA 206VE UT WOS:000323551200010 PM 23733179 ER PT J AU Goel, S Gupta, N Walcott, BP Snuderl, M Kesler, CT Kirkpatrick, ND Heishi, T Huang, YH Martin, JD Ager, E Samuel, R Wang, SH Yazbek, J Vakoc, BJ Peterson, RT Padera, TP Duda, DG Fukumura, D Jain, RK AF Goel, Shom Gupta, Nisha Walcott, Brian P. Snuderl, Matija Kesler, Cristina T. Kirkpatrick, Nathaniel D. Heishi, Takahiro Huang, Yuhui Martin, John D. Ager, Eleanor Samuel, Rekha Wang, Shuhan Yazbek, John Vakoc, Benjamin J. Peterson, Randall T. Padera, Timothy P. Duda, Dan G. Fukumura, Dai Jain, Rakesh K. TI Effects of Vascular-Endothelial Protein Tyrosine Phosphatase Inhibition on Breast Cancer Vasculature and Metastatic Progression SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BLOOD-VESSEL DEVELOPMENT; TUMOR-GROWTH; OVEREXPRESSING ANGIOPOIETIN-1; ANTIANGIOGENIC THERAPY; ANGIOGENESIS; NORMALIZATION; VEGF; SURVIVAL; OXYGENATION; PERFUSION AB The solid tumor microvasculature is characterized by structural and functional abnormality and mediates several deleterious aspects of tumor behavior. Here we determine the role of vascular endothelial protein tyrosine phosphatase (VE-PTP), which deactivates endothelial cell (EC) Tie-2 receptor tyrosine kinase, thereby impairing maturation of tumor vessels. AKB-9778 is a first-in-class VE-PTP inhibitor. We examined its effects on ECs in vitro and on embryonic angiogenesis in vivo using zebrafish assays. We studied the impact of AKB-9778 therapy on the tumor vasculature, tumor growth, and metastatic progression using orthotopic models of murine mammary carcinoma as well as spontaneous and experimental metastasis models. Finally, we used endothelial nitric oxide synthase (eNOS)deficient mice to establish the role of eNOS in mediating the effects of VE-PTP inhibition. All statistical tests were two-sided. AKB-9778 induced ligand-independent Tie-2 activation in ECs and impaired embryonic zebrafish angiogenesis. AKB-9778 delayed the early phase of mammary tumor growth by maintaining vascular maturity (P < .01, t test); slowed growth of micrometastases (P < .01, (2) test) by preventing extravasation of tumor cells (P < 0.01, Fisher exact test), resulting in a trend toward prolonged survival (27.0 vs 36.5 days; hazard ratio of death 0.33, 95% confidence interval 0.11 to 1.03; P .05, MantelCox test); and stabilized established primary tumor blood vessels, enhancing tumor perfusion (P .03 for 4T1 tumor model and 0.05 for E0771 tumor model, by two-sided t tests) and, hence, radiation response (P < .01, analysis of variance; n 7 mice per group). The effects of AKB-9778 on tumor vessels were mediated in part by endothelial nitric oxide synthase activation. Our results demonstrate that pharmacological VE-PTP inhibition can normalize the structure and function of tumor vessels through Tie-2 activation, which delays tumor growth, slows metastatic progression, and enhances response to concomitant cytotoxic treatments. C1 [Goel, Shom; Gupta, Nisha; Snuderl, Matija; Kesler, Cristina T.; Kirkpatrick, Nathaniel D.; Heishi, Takahiro; Huang, Yuhui; Martin, John D.; Ager, Eleanor; Samuel, Rekha; Padera, Timothy P.; Duda, Dan G.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. [Vakoc, Benjamin J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Walcott, Brian P.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Walcott, Brian P.; Peterson, Randall T.] Harvard Univ, Sch Med, Charlestown, MA USA. [Wang, Shuhan] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yazbek, John] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Cox 7,100 Blossom St, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu RI Martin, John/L-6892-2016; OI Martin, John/0000-0002-9828-8203; Ager, Eleanor/0000-0002-7849-9206; Huang, Yuhui/0000-0003-1985-3575; Padera, Timothy/0000-0002-3453-9384; Snuderl, Matija/0000-0003-0752-0917 FU NCI NIH HHS [R01 CA163528, 2K12CA090354-11, P01-CA080124, R00 CA137167, R00-CA137167, R01-CA096915, R01-CA126642, R01-CA159258, R01-CA163528, T32-CA073479]; NCRR NIH HHS [S10-RR027070]; NIBIB NIH HHS [P41 EB015903, P41EB015903]; NIH HHS [DP2 OD008780, DP2OD008780] NR 41 TC 27 Z9 28 U1 2 U2 18 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 AUG PY 2013 VL 105 IS 16 BP 1188 EP 1201 DI 10.1093/jnci/djt164 PG 14 WC Oncology SC Oncology GA 207YR UT WOS:000323641300008 PM 23899555 ER PT J AU Hasham, A Zhang, WJ Lotay, V Haggerty, S Stefan, M Concepcion, E Dieterich, DT Tomer, Y AF Hasham, Alia Zhang, Weijia Lotay, Vaneet Haggerty, Shannon Stefan, Mihaela Concepcion, Erlinda Dieterich, Douglas T. Tomer, Yaron TI Genetic analysis of interferon induced thyroiditis (IIT): Evidence for a key role for MHC and apoptosis related genes and pathways SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Interferon; Thyroiditis; Autoimmunity; Thyroid ID CHRONIC HEPATITIS-C; GRAVES-DISEASE; AUTOIMMUNITY; ALPHA; ASSOCIATION; POPULATION; CELLS; TAP1; PML; POLYMORPHISMS AB Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFN alpha) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFN alpha and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFN alpha treatment. However, the exact mechanisms that lead to the development of IIT are unknown and may include IFN alpha-mediated immune-recruitment as well as direct toxic effects on thyroid follicular cells. We hypothesized that IIT develops in genetically predisposed individuals whose threshold for developing thyroiditis is lowered by IFN alpha. Therefore, our aim was to identify the susceptibility genes for IIT. We used a genomic convergence approach combining genetic association data with transcriptome analysis of genes upregulated by IFN alpha. Integrating results of genetic association, transcriptome data, pathway, and haplotype analyses enabled the identification of 3 putative loci, SP100/110/140 (2q37.1), HLA (6p21.3), and TAP1 (6p21.3) that may be involved in the pathogenesis of IIT. Immune-regulation and apoptosis emerged as the predominant mechanisms underlying the etiology of IIT. (C) Published by Elsevier Ltd. C1 [Hasham, Alia; Stefan, Mihaela; Concepcion, Erlinda; Tomer, Yaron] Mt Sinai Sch Med, Dept Med, Div Endocrinol, New York, NY USA. [Hasham, Alia; Stefan, Mihaela; Tomer, Yaron] James J Peters VA Med Ctr, Bronx, NY USA. [Zhang, Weijia; Lotay, Vaneet] Mt Sinai Sch Med, Dept Med Bioinformat Core, New York, NY USA. [Haggerty, Shannon] Univ Cincinnati, Coll Med, Div Endocrinol, Cincinnati, OH USA. [Dieterich, Douglas T.] Mt Sinai Sch Med, Dept Med, Div Liver Dis, New York, NY USA. RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Div Endocrinol, Box 1055,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Yaron.Tomer@mssm.edu FU VA Merit award from Department of Veterans Affairs [1I01BX002031]; NIDDK [DK61659, DK073681] FX This work was supported in part by a VA Merit award 1I01BX002031 from the Department of Veterans Affairs, and by grants DK61659, and DK073681 from NIDDK (to YT). We thank Dr. David A. Greenberg (Battelle Center for Mathematical Medicine and Department of Neurology, Nationwide Children's Hospital, Columbus, Ohio) for his suggestions and expert review of this manuscript. NR 39 TC 7 Z9 10 U1 3 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD AUG PY 2013 VL 44 BP 61 EP 70 DI 10.1016/j.jaut.2013.04.002 PG 10 WC Immunology SC Immunology GA 208PJ UT WOS:000323691300008 PM 23683877 ER PT J AU Benz, EJ Nathan, DG AF Benz, Edward J., Jr. Nathan, David G. TI A tribute to Emil Frei III Obituary SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Biographical-Item C1 [Benz, Edward J., Jr.; Nathan, David G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benz, EJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM edward_benz@dfci.harvard.edu; David_Nathan@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 2013 VL 123 IS 8 BP 3188 EP 3189 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196CH UT WOS:000322750500002 ER PT J AU Richardson, A AF Richardson, Arlan TI Rapamycin, anti-aging, and avoiding the fate of Tithonus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID EXTENDS LIFE-SPAN; GENETICALLY HETEROGENEOUS MICE; MAMMALIAN TARGET; MTOR; INHIBITION AB The discovery that rapamycin increased the lifespan of mice was recognized by Science as one of the top 10 scientific breakthroughs of 2009. In addition to increasing lifespan, Neff and colleagues show that while rapamycin improves several functions/pathologies that change with age, it has little effect on the majority of the physiological and structural parameters they evaluated. What do these data tell us about the ability of rapamycin to delay aging and improve quality of life, i.e., prevent the fate of Tithonus? C1 [Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Richardson, Arlan] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Richardson, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM richardsona@uthscsa.edu FU NIA NIH HHS [RC2 AG036613] NR 23 TC 12 Z9 12 U1 0 U2 3 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 AUG PY 2013 VL 123 IS 8 BP 3204 EP 3206 DI 10.1172/JCI70800 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196CH UT WOS:000322750500005 PM 24063054 ER PT J AU Woo, AJ Wieland, K Huang, H Akie, TE Piers, T Kim, J Cantor, AB AF Woo, Andrew J. Wieland, Karen Huang, Hui Akie, Thomas E. Piers, Taylor Kim, Jonghwan Cantor, Alan B. TI Developmental differences in IFN signaling affect GATA1s-induced megakaryocyte hyperproliferation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE MEGAKARYOBLASTIC LEUKEMIA; TRANSIENT MYELOPROLIFERATIVE DISORDER; RECOMBINANT INTERFERON-ALPHA; DOWN-SYNDROME; GATA1 MUTATIONS; GENE-EXPRESSION; ACQUIRED MUTATIONS; MYELOID-LEUKEMIA; NATURAL-HISTORY; MEGAKARYOPOIESIS AB About 10% of Down syndrome (DS) infants are born with a transient myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20%-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). Somatic mutations leading to the exclusive production of a short GATA1 isoform (GATA1s) occur in all cases of DS-TMD and DS-AMKL. Mice engineered to exclusively produce GATA1s have marked megakaryocytic progenitor (MkP) hyperproliferation during early fetal liver (FL) hematopoiesis, but not during postnatal BM hematopoiesis, mirroring the spontaneous resolution of DS-TMD. The mechanisms that underlie these developmental stage-specific effects are incompletely understood. Here, we report a striking upregulation of type I IFN-responsive gene expression in prospectively isolated mouse BM- versus FL-derived MkPs. Exogenous IFN-alpha markedly reduced the hyperproliferation FL-derived MkPs of GATA1s mice in vitro. Conversely, deletion of the alpha/beta IFN receptor 1 (Ifnar1) gene or injection of neutralizing IFN-alpha/beta antibodies increased the proliferation of BM-derived MkPs of GATA1s mice beyond the initial postnatal period. We also found that these differences existed in human FL versus BM mega-karyocytes and that primary DS-TMD cells expressed type I IFN-responsive genes. We propose that increased type I IFN signaling contributes to the developmental stage-specific effects of GATA1s and possibly the spontaneous resolution of DS-TMD. C1 [Woo, Andrew J.; Wieland, Karen; Huang, Hui; Akie, Thomas E.; Piers, Taylor; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA. [Kim, Jonghwan] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Cantor, Alan B.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Cantor, AB (reprint author), Childrens Hosp Boston, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA. EM alan.cantor@childrens.harvard.edu FU German Academic Research Service; NIH [R01 HL075705]; American Society for Hematology FX We thank Stuart Orkin for providing GATA1s mice, Genhong Cheng for providing Ifnar1-/- mice, Jonathan Keller for providing the Ifi205 (p205) antibody, Mark Fleming and Theonia Boyd for assisting with procurement of human BM and FL pathology specimens, and Andrei Kristov and Grigoriy Losyev for advice and assistance with cell sorting. We thank Zhe Li and Martha Sola-Visner for advice and critical review of the manuscript. This work was supported by grants from the German Academic Research Service (to K. Wieland), the NIH (R01 HL075705; to A.B. Cantor), and the American Society for Hematology (to A.B. Cantor). NR 44 TC 5 Z9 5 U1 0 U2 1 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 AUG PY 2013 VL 123 IS 8 BP 3292 EP 3304 DI 10.1172/JCI40609 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196CH UT WOS:000322750500013 ER PT J AU Navaratna, D Fan, X Leung, W Lok, J Guo, SZ Xing, CH Wang, XY Lo, EH AF Navaratna, Deepti Fan, Xiang Leung, Wendy Lok, Josephine Guo, Shuzhen Xing, Changhong Wang, Xiaoying Lo, Eng H. TI Cerebrovascular degradation of TRKB by MMP9 in the diabetic brain SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID KUNGSHOLMEN PROJECT; ISCHEMIC-STROKE; APOE GENE; DEMENTIA; RISK; MELLITUS; NEURONS; CELLS AB Diabetes elevates the risk for neurological diseases, but little is known about the underlying mechanisms. Brain-derived neurotrophic factor (BDNF) is secreted by microvascular endothelial cells (ECs) in the brain, functioning as a neuroprotectant through the activation of the neurotrophic tyrosine kinase receptor TRKB. In a rat model of streptozotocin-induced hyperglycemia, we found that endothelial activation of MMP9 altered TRKB-dependent trophic pathways by degrading TRKB in neurons. Treatment of brain microvascular ECs with advanced glycation endproducts (AGE), a metabolite commonly elevated in diabetic patients, increased MMP9 activation, similar to in vivo findings. Recombinant human MMP9 degraded the TRKB ectodomain in primary neuronal cultures, suggesting that TRKB could be a substrate for MMP9 proteolysis. Consequently, AGE-conditioned endothelial media with elevated MMP9 activity degraded the TRKB ectodomain and simultaneously disrupted the ability of endothelium to protect neurons against hypoxic injury. Our findings demonstrate that neuronal TRKB trophic function is ablated by MMP9-mediated degradation in the diabetic brain, disrupting cerebrovascular trophic coupling and leaving the brain vulnerable to injury. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Pediat, Charlestown, MA USA. RP Lo, EH (reprint author), Neuroprotect Res Lab, MGH East 149-2401,13th St, Charlestown, MA 02129 USA. EM deeptinavaratna@gmail.com; Lo@helix.mgh.harvard.edu FU NIH [R01-NS76694, RC2-NS69335, P01-NS55104]; American Heart Founders Postdoctoral Fellowship; Rappaport Foundation FX This work was supported in part by NIH grants (R01-NS76694, RC2-NS69335, P01-NS55104), an American Heart Founders Postdoctoral Fellowship, and the Rappaport Foundation. NR 14 TC 6 Z9 8 U1 0 U2 4 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 AUG PY 2013 VL 123 IS 8 BP 3373 EP 3377 DI 10.1172/JCI65767 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196CH UT WOS:000322750500020 PM 23867621 ER PT J AU Arora, P Wu, C Khan, AM Bloch, DB Davis-Dusenbery, BN Ghorbani, A Spagnolli, E Martinez, A Ryan, A Tainsh, LT Kim, S Rong, J Huan, TX Freedman, JE Levy, D Miller, KK Hata, A del Monte, F Vandenwijngaert, S Swinnen, M Janssens, S Holmes, TM Buys, ES Bloch, KD Newton-Cheh, C Wang, TJ AF Arora, Pankaj Wu, Connie Khan, Abigail May Bloch, Donald B. Davis-Dusenbery, Brandi N. Ghorbani, Anahita Spagnolli, Ester Martinez, Andrew Ryan, Allicia Tainsh, Laurel T. Kim, Samuel Rong, Jian Huan, Tianxiao Freedman, Jane E. Levy, Daniel Miller, Karen K. Hata, Akiko del Monte, Federica Vandenwijngaert, Sara Swinnen, Melissa Janssens, Stefan Holmes, Tara M. Buys, Emmanuel S. Bloch, Kenneth D. Newton-Cheh, Christopher Wang, Thomas J. TI Atrial natriuretic peptide is negatively regulated by microRNA-425 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BLOOD-PRESSURE; SODIUM-INTAKE; TARGETS; ASSOCIATION AB Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable. to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure. C1 [Arora, Pankaj; Ghorbani, Anahita; Martinez, Andrew; Ryan, Allicia; Bloch, Kenneth D.; Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Arora, Pankaj; Ghorbani, Anahita; Bloch, Kenneth D.; Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Arora, Pankaj; Martinez, Andrew; Ryan, Allicia; Kim, Samuel; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Arora, Pankaj; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Wu, Connie; Spagnolli, Ester; Tainsh, Laurel T.; Buys, Emmanuel S.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Khan, Abigail May] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Clin Immunol, Boston, MA 02114 USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Davis-Dusenbery, Brandi N.] Harvard Univ, Cambridge, MA 02138 USA. [Rong, Jian; Huan, Tianxiao; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA. [Rong, Jian; Huan, Tianxiao; Levy, Daniel] Boston Univ, Sch Med, Framingham, MA USA. [Rong, Jian; Huan, Tianxiao; Levy, Daniel] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Rong, Jian; Huan, Tianxiao; Levy, Daniel] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Div Endocrinol, Boston, MA 02114 USA. [Hata, Akiko] UCSF, Cardiovasc Res Inst, San Francisco, CA USA. [del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Vandenwijngaert, Sara; Swinnen, Melissa; Janssens, Stefan] Univ Louvain, Univ Hosp Gasthuisberg, Dept Cardiovasc Sci, Louvain, Belgium. [Holmes, Tara M.] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37232 USA. RP Bloch, KD (reprint author), Anesthesia Ctr Crit Care Res, Dept Anesthesia & Crit Care, Jackson 4,55 Fruit St, Boston, MA 02114 USA. EM kdbloch@partners.org; cnewtoncheh@chgr.mgh.harvard.edu; thomas.j.wang@vanderbilt.edu RI Huan, Tianxiao/D-6020-2014; Davis-Dusenbery, Brandi/N-2798-2013; OI Davis-Dusenbery, Brandi/0000-0001-7811-8613; Arora, Pankaj/0000-0003-2420-3550 FU NIH [R01-HL098283]; National Center for Research Resources [1 UL1-RR025758-01]; Fondation LeDucq; Research Council of the University of Leuven [PF/10/014] FX The authors thank the Massachusetts General Hospital Clinical Research Center staff and the Center for Human Genetic Research extraction and genotyping core. We also acknowledge support from NIH R01-HL098283 and 1 UL1-RR025758-01 from the National Center for Research Resources. The research was also supported by a grant from the Fondation LeDucq and from the Research Council of the University of Leuven (PF/10/014). NR 13 TC 40 Z9 42 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 AUG PY 2013 VL 123 IS 8 BP 3378 EP 3382 DI 10.1172/JCI67383 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196CH UT WOS:000322750500021 PM 23867623 ER PT J AU van der Lans, AAJJ Hoeks, J Brans, B Vijgen, GHEJ Visser, MGW Vosselman, MJ Hansen, J Jorgensen, JA Wu, J Mottaghy, FM Schrauwen, P Lichtenbelt, WDV AF van der Lans, Anouk A. J. J. Hoeks, Joris Brans, Boudewijn Vijgen, Guy H. E. J. Visser, Marielle G. W. Vosselman, Maarten J. Hansen, Jan Joergensen, Johanna A. Wu, Jun Mottaghy, Felix M. Schrauwen, Patrick Lichtenbelt, Wouter D. van Marken TI Cold acclimation recruits human brown fat and increases nonshivering thermogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INDUCED ADAPTIVE THERMOGENESIS; ADIPOSE-TISSUE ACTIVITY; SKELETAL-MUSCLE; PHYSIOLOGICAL SIGNIFICANCE; MITOCHONDRIAL DYSFUNCTION; ENERGY-EXPENDITURE; ADULT HUMANS; TEMPERATURE; ADIPOCYTES; RESPONSES AB In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show "browning" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic. C1 [van der Lans, Anouk A. J. J.; Hoeks, Joris; Vijgen, Guy H. E. J.; Vosselman, Maarten J.; Hansen, Jan; Joergensen, Johanna A.; Schrauwen, Patrick; Lichtenbelt, Wouter D. van Marken] MUMC, Dept Human Biol, NUTRIM, Sch Nutr Toxicol & Metab, Maastricht, Netherlands. [Brans, Boudewijn; Visser, Marielle G. W.; Mottaghy, Felix M.] MUMC, Dept Nucl Med, Maastricht, Netherlands. [Vijgen, Guy H. E. J.] MUMC, Dept Surg, Maastricht, Netherlands. [Wu, Jun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wu, Jun] Harvard Univ, Sch Med, Boston, MA USA. [Mottaghy, Felix M.] Univ Hosp RWTH Aachen, Dept Nucl Med, Aachen, Germany. RP Lichtenbelt, WDV (reprint author), Maastricht Univ, Dept Human Biol, NUTRIM, Sch Nutr Toxicol & Metab, POB 616, NL-6200 MD Maastricht, Netherlands. EM markenlichtenbelt@maastrichtuniversity.nl OI schrauwen, patrick/0000-0002-0973-847X FU Netherlands Organization for Scientific Research [TOP 91209037]; EU [HEALTH-F2-2011-278373] FX This work is financed by the Netherlands Organization for Scientific Research (TOP 91209037 to W.D. van Marken Lichtenbelt) and by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to W.D. van Marken Lichtenbelt). We thank Sabina Paglialunga and Kyra Jansen (Maastricht University Medical Centre+) for assistance during the experiments and Ivo Pooters, Matthias Bauwens, Nancy Hendrix, Paul Menheere, and Jos Stegen (Maastricht University Medical Centre+) for their assistance with the biochemical analyses. Furthermore technical support of Boris Kingma, Roel Wierts, Loek Wouters, and Paul Schoffelen (Maastricht University Medical Centre+) is highly appreciated Finally, we thank our Literature Club for all the fruitful discussions. NR 49 TC 200 Z9 200 U1 18 U2 71 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 AUG PY 2013 VL 123 IS 8 BP 3395 EP 3403 DI 10.1172/JCI68993 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196CH UT WOS:000322750500023 PM 23867626 ER PT J AU Ramsey, MR Wilson, C Ory, B Rothenberg, SM Faquin, W Mills, AA Ellisen, LW AF Ramsey, Matthew R. Wilson, Catherine Ory, Benjamin Rothenberg, S. Michael Faquin, William Mills, Alea A. Ellisen, Leif W. TI FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; GROWTH-FACTOR; NECK-CANCER; TUMOR PROGRESSION; METASTATIC HEAD; SKIN TUMORS; MOUSE MODEL; EXPRESSION; MICE AB Oncogenic transcription factors drive many human cancers, yet identifying and therapeutically targeting the resulting deregulated pathways has proven difficult. Squamous cell carcinoma (SCC) is a common and lethal human cancer, and relatively little progress has been made in improving outcomes for SCC due to a poor understanding of its underlying molecular pathogenesis. While SCCs typically lack somatic oncogene-activating mutations, they exhibit frequent overexpression of the p53-related transcription factor p63. We developed an in vivo murine tumor model to investigate the function and key transcriptional programs of p63 in SCC. Here, we show that established SCCs are exquisitely dependent on p63, as acute genetic ablation of p63 in advanced, invasive SCC induced rapid and dramatic apoptosis and tumor regression. In vivo genome-wide gene expression analysis identified a tumor-survival program involving p63-regulated FGFR2 signaling that was activated by ligand emanating from abundant tumor-associated stroma. Correspondingly, we demonstrate the therapeutic efficacy of extinguishing this signaling axis in endogenous SCCs using the clinical FGFR2 inhibitor AZD4547. Collectively, these results reveal an unanticipated role for p63-driven paracrine FGFR2 signaling as an addicting pathway in human cancer and suggest a new approach for the treatment of SCC. C1 [Ramsey, Matthew R.; Wilson, Catherine; Ory, Benjamin; Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ramsey, Matthew R.; Wilson, Catherine; Ory, Benjamin; Rothenberg, S. Michael; Faquin, William; Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA USA. [Rothenberg, S. Michael; Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mills, Alea A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ 904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu RI ory, benjamin/K-8231-2015; OI Ramsey, Matthew/0000-0003-2402-8502 FU NIDCR [R01 DE015945]; NCI [K99 CA 157730]; American Cancer Society/Mass Biotech Council Cancer Research Challenge-AstraZeneca Pharmaceuticals LP Fellowship [PF-09-100-01 MGO] FX We wish to thank Nabeel Bardeesy, James Rocco, William Michaud, Mike Dennis, and Zach Nash for advice, reagents, and technical support; and Nabeel Bardeesy, Andrea McClatchey, and members of the Ellisen laboratory for comments on the manuscript. The Dana-Farber/Harvard Cancer Center Specialized Histopathology Core Facility assisted in processing and staining of murine tumors, and the Harvard Stem Cell Institute/Center for Regenerative Medicine (HSCI/CRM) Flow Cytometry Core Facility assisted with tumor sample sorting. AZD4547 used in this study was provided by AstraZeneca Pharmaceuticals LP. This work was supported by NIDCR R01 DE015945 (to L.W. Ellisen), by NCI K99 CA 157730 (to M.R. Ramsey), and by the American Cancer Society/Mass Biotech Council Cancer Research Challenge-AstraZeneca Pharmaceuticals LP Fellowship PF-09-100-01 MGO (to M.R. Ramsey). NR 81 TC 35 Z9 35 U1 3 U2 16 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 AUG PY 2013 VL 123 IS 8 BP 3525 EP 3538 DI 10.1172/JCI68899 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196CH UT WOS:000322750500034 PM 23867503 ER PT J AU Gabrielian, S Yuan, A Rubenstein, L Andersen, RM Gelberg, L AF Gabrielian, Sonya Yuan, Anita Rubenstein, Lisa Andersen, Ronald M. Gelberg, Lillian TI Serving homeless Veterans in the VA Desert Pacific Healthcare Network: A needs assessment to inform quality improvement endeavors SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Homeless people; Veterans; quality improvement; needs assessment ID SERIOUS MENTAL-ILLNESS; MEDICAL-CARE; ADULTS AB This report describes a needs assessment of VA programs for homeless Veterans in Southern California and Nevada, the geographic region with the most homeless Veterans in the nation. The assessment was formulated through key informant interviews. Current service provisions are discussed, along with salient unmet needs for this vulnerable population. C1 [Gabrielian, Sonya; Gelberg, Lillian] Vet Adm Greater Los Angeles, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA. [Yuan, Anita] VA GLA, Dept Primary Care, Los Angeles, CA USA. [Rubenstein, Lisa] VA GLA, Hlth Serv Res & Dev Ctr Excellence Study Healthca, Los Angeles, CA USA. [Rubenstein, Lisa] RAND Corp, Santa Monica, CA 90406 USA. [Andersen, Ronald M.; Gelberg, Lillian] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Gelberg, Lillian] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90024 USA. RP Gabrielian, S (reprint author), VA Greater Los Angeles WLA, 11301 Wilshire Blvd,Bldg 210A, Los Angeles, CA 90073 USA. EM sonya.gabrielian@va.gov FU Intramural VA [VA999999]; NIDA NIH HHS [R01 DA022445, DA 022445]; NIMHD NIH HHS [P20MD000148/P20MD000182, P20 MD000148, P20 MD000182] NR 18 TC 0 Z9 0 U1 0 U2 8 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 2013 VL 24 IS 3 BP 1344 EP 1352 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 206OR UT WOS:000323532500033 PM 23974403 ER PT J AU Prabhakar, AM Harvey, HB Wicky, S Hirsch, JA Thrall, JH Oklu, R AF Prabhakar, Anand M. Harvey, H. Benjamin Wicky, Stephan Hirsch, Joshua A. Thrall, James H. Oklu, Rahmi TI What's Brewing: How Interventional Radiologists Can Learn From the Reinvention of Starbucks SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Prabhakar, Anand M.; Harvey, H. Benjamin; Wicky, Stephan; Hirsch, Joshua A.; Thrall, James H.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM amp@alumni.upenn.edu NR 19 TC 2 Z9 2 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD AUG PY 2013 VL 10 IS 8 BP 559 EP 561 DI 10.1016/j.jacr.2012.12.021 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204UP UT WOS:000323397000004 PM 23453724 ER PT J AU Iii, E Breslau, J Barr, RM Liebscher, LA Bohl, M Hoffman, T Boland, GWL Sherry, C Kim, W Shah, SS Tilking, M AF Silva, Ezequiel, III Breslau, Jonathan Barr, Robert M. Liebscher, Lawrence A. Bohl, Michael Hoffman, Thomas Boland, Giles W. L. Sherry, Cynthia Kim, Woojin Shah, Samir S. Tilking, Mike TI ACR White Paper on Teleradiology Practice: A Report From the Task Force on Teleradiology Practice SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Quality of care; technology; teleradiology; teleradiologist; teleradiology company; regulatory issues; end-user standards; patient primacy; business standards of practice; disintermediation ID RADIOLOGY; MALPRACTICE; ERGONOMICS; PACS AB Teleradiology services are now embedded into the workflow of many radiology practices in the United States, driven largely by an expanding corporate model of services. This has brought opportunities and challenges to both providers and recipients of teleradiology services and has heightened the need to create best-practice guidelines for teleradiology to ensure patient primacy. To this end, the ACR Task Force on Teleradiology Practice has created this white paper to update the prior ACR communication on teleradiology and discuss the current and possible future state of teleradiology in the United States. This white paper proposes comprehensive best-practice guidelines for the practice of teleradiology, with recommendations offered regarding future actions. C1 [Silva, Ezequiel, III] South Texas Radiol Grp, San Antonio, TX 78229 USA. [Silva, Ezequiel, III] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Breslau, Jonathan] Radiol Associates Sacramento Med Grp Inc, Sacramento, CA USA. [Barr, Robert M.] Mecklenburg Radiol Associates, Charlotte, NC USA. [Liebscher, Lawrence A.] Cedar Valley Med Specialists, Waterloo, IA USA. [Bohl, Michael] Radliol Grp, Davenport, IA USA. [Hoffman, Thomas; Tilking, Mike] Amer Coll Radiol, Reston, VA USA. [Boland, Giles W. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sherry, Cynthia] Texas Hlth Presbyterian Hosp, Dallas, TX USA. [Kim, Woojin] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shah, Samir S.] Virtual Radiol, Eden Prairie, MN USA. RP Iii, E (reprint author), South Texas Radiol Grp, 8401 Datapoint,Suite 600, San Antonio, TX 78229 USA. EM zeitesilva3@gmail.com OI Barr, Robert/0000-0002-9214-9448 NR 40 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD AUG PY 2013 VL 10 IS 8 BP 575 EP 585 DI 10.1016/j.jacr.2013.03.018 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204UP UT WOS:000323397000009 ER PT J AU Bhargava, P Robinson, TJ Lyer, RS Seyal, AR Munsell, A Moshiri, M Dighe, MK Richardson, ML Weinberger, E AF Bhargava, Puneet Robinson, Tracy J. Lyer, Ramesh S. Seyal, Adeel R. Munsell, Andrew Moshiri, Mariam Dighe, Manjiri K. Richardson, Michael L. Weinberger, Edward TI Sharing a Collection of Radiology Educational Websites as Bookmarks Among Radiologists SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID RESOURCES; INTERNET; FUTURE C1 [Bhargava, Puneet; Robinson, Tracy J.; Lyer, Ramesh S.; Munsell, Andrew; Moshiri, Mariam; Dighe, Manjiri K.; Richardson, Michael L.; Weinberger, Edward] Univ Washington, Sch Med, Dept Radiol, Seattle, WA USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lyer, Ramesh S.; Munsell, Andrew; Weinberger, Edward] Seattle Childrens Hosp, Seattle, WA USA. [Seyal, Adeel R.] Harrison Med Ctr, Bremerton, WA USA. RP Bhargava, P (reprint author), VA Puget Sound Hlth Care Syst, Dept Radiol, 1660 S Columbian Way,Mailbox 358280,S-114-Radiol, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 8 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD AUG PY 2013 VL 10 IS 8 BP 627 EP 632 DI 10.1016/j.jacr.2012.12.015 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 204UP UT WOS:000323397000017 PM 23453725 ER PT J AU Mitin, T Hunt, D Shipley, WU Kaufman, DS Uzzo, R Wu, CL Buyyounouski, MK Sandler, H Zietman, AL AF Mitin, Timur Hunt, Daniel Shipley, William U. Kaufman, Donald S. Uzzo, Robert Wu, Chin-Lee Buyyounouski, Mark K. Sandler, Howard Zietman, Anthony L. TI Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; RADICAL CYSTECTOMY; ORGAN PRESERVATION; RESECTION; THERAPY; RADIOTHERAPY; SERIES AB Background We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer. Methods In our randomised phase 2 trial, we enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA. We randomly allocated patients to receive paclitaxel plus cisplatin (paclitaxel group) or fluorouracil plus cisplatin (fluorouracil group) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage (T2 vs T3-4). Patients and physicians were aware of treatment assignment. All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40.3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64.3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemo radiotherapy. If, after induction, persistent disease was graded as T1 or worse, we recommended patients undergo cystectomy and adjuvant chemotherapy. We assessed the primary endpoints of rates of treatment completion and toxic effects in all randomly allocated patients. This study is registered with ClinicalTrials.gov, number NCT00055601. Findings Between Dec 13, 2002, and Jan 11, 2008, we enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5.0 years (IQR 5.0-6.2). Of 46 patients in the paclitaxel group, 45 (98%) completed induction (16 [35%] with grade 3-4 toxicity), 39 (85%) completed induction and consolidation (11 [24%] with grade 3-4 toxicity due to consolidation), and 31 (67%) completed the entire protocol with adjuvant chemotherapy. 34 (85%) of 40 assessable patients in the paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy. Of 47 patients in the fluorouracil group, 45 (96%) completed induction (nine [19%] with grade 3-4 toxicity), 39 (83%) completed induction and consolidation (12 [26%] had grade 3-4 toxicity due to consolidation), and 25 (53%) completed the entire protocol with adjuvant chemotherapy. 31 (76%) of 41 assessable patients in the fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy. Five (11%) patients treated with the paclitaxel regimen and three (6%) patients treated with the fluorouracil regimen developed late grade 3-4 radiotherapy toxicities. 11 (24%) patients treated with the paclitaxel regimen and 16 (34%) patients treated with the fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy. One patient (in the fluorouracil group) died during follow-up. Six (13%) patients in the paclitaxel group and in three (6%) patients in the fluorouracil group discontinued due to treatment-related toxicity. Interpretation In the absence of phase 3 data, our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer. C1 [Mitin, Timur; Shipley, William U.; Kaufman, Donald S.; Wu, Chin-Lee; Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hunt, Daniel] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Uzzo, Robert; Buyyounouski, Mark K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Sandler, Howard] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Mitin, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM tmitin@partners.org FU RTOG [U10 CA21661]; Community Clinical Oncology Program grant from the US National Cancer Institute (NCI) [U10 CA37422] FX This trial was undertaken by the RTOG, and was supported by RTOG grant U10 CA21661 and Community Clinical Oncology Program grant U10 CA37422 from the US National Cancer Institute (NCI). NR 32 TC 34 Z9 34 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2013 VL 14 IS 9 BP 863 EP 872 DI 10.1016/S1470-2045(13)70255-9 PG 10 WC Oncology SC Oncology GA 205DZ UT WOS:000323423400043 PM 23823157 ER PT J AU Barton, SE Najita, JS Ginsburg, ES Leisenring, WM Stovall, M Weathers, RE Sklar, CA Robison, LL Diller, L AF Barton, Sara E. Najita, Julie S. Ginsburg, Elizabeth S. Leisenring, Wendy M. Stovall, Marilyn Weathers, Rita E. Sklar, Charles A. Robison, Leslie L. Diller, Lisa TI Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort SO LANCET ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; ANTI-MULLERIAN HORMONE; DOSE RECONSTRUCTION; HODGKINS LYMPHOMA; OVARIAN FAILURE; BREAST-CANCER; CHEMOTHERAPY; FERTILITY; WOMEN; RADIOTHERAPY AB Background Previous studies have shown decreased pregnancy rates and early menopause in female cancer survivors; however, infertility rates and reproductive interventions have not been studied. We investigated infertility and time to pregnancy in female childhood cancer survivors, and analysed treatment characteristics associated with infertility and subsequent pregnancy. Methods The Childhood Cancer Survivor Study (CCSS) is a cohort study including 5 year cancer survivors from 26 Canadian and US institutions who were younger than 21 years at the time of diagnosis between Jan 1, 1970, and Dec 31, 1986, and a sibling control group. We included women aged 18-39 years who had ever been sexually active. We gathered demographic, medical, and reproductive data via a baseline questionnaire, and quantified exposure to alkylating agents and radiation therapy. Self-reported infertility, medical treatment for infertility, time to first pregnancy in survivors and siblings, and the risk of infertility in survivors by demographic, disease, and treatment variables were analysed. Findings 3531 survivors and 1366 female sibling controls who enrolled between Nov 3, 1992, and April 4, 2004, were included. Compared with their siblings, survivors had an increased risk (relative risk [RR] 1.48 [95% CI 1.23-1.78]; p<0.0001) of clinical infertility (ie, >1 year of attempts at conception without success), which was most pronounced at early reproductive ages (RR 2.92 [95% CI 1.18-7.20], p=0.020, in participants <= 24 years; 1.61 [1.05-2.48], p=0.029, in those aged 25-29 years; and 1.37 [1.11-1.69], p=0.0035, in those aged 30-40 years). Despite being equally likely to seek treatment for infertility, survivors were less likely than were their siblings to be prescribed drugs for treatment of infertility (0.57 [95% CI 0.46-0.70], p<0.0001). Increasing doses of uterine radiation and alkylating agent chemotherapy were strongly associated with infertility. Although survivors had an increased time to pregnancy compared with their siblings (p=0.032), 292 (64%) of 455 participants with self-reported clinical infertility achieved a pregnancy. Interpretation A more comprehensive understanding of infertility after cancer is crucial for counselling and decision making about future conception attempts and fertility preservation. C1 [Barton, Sara E.; Ginsburg, Elizabeth S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Barton, Sara E.; Ginsburg, Elizabeth S.] Harvard Univ, Sch Med, Boston, MA USA. [Najita, Julie S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Clin Stat Program, Seattle, WA 98104 USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Stovall, Marilyn; Weathers, Rita E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN USA. [Diller, Lisa] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Diller, Lisa] Dana Farber Boston Childrens Hosp Canc Ctr, Boston, MA USA. RP Barton, SE (reprint author), Brigham & Womens Hosp, Ctr Infertil & Reprod Surg, 75 Francis St, Boston, MA 02115 USA. EM sarabarton5@gmail.com FU US National Cancer Institute [U24 CA55727]; American Lebanese Syrian Associated Charities; Swim Across America FX This study was funded by grant U24 CA55727 (awarded to LLR, the principal investigator) from the US National Cancer Institute, support to St Jude Children's Research Hospital from the American Lebanese Syrian Associated Charities, and support to LD from Swim Across America. NR 29 TC 62 Z9 63 U1 4 U2 19 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 AUG PY 2013 VL 14 IS 9 BP 873 EP 881 DI 10.1016/S1470-2045(13)70251-1 PG 9 WC Oncology SC Oncology GA 205DZ UT WOS:000323423400044 PM 23856401 ER PT J AU Quinn, DI Tangen, CM Hussain, M Lara, PN Goldkorn, A Moinpour, CM Garzotto, MG Mack, PC Carducci, MA Monk, JP Twardowski, PW Van Veldhuizen, PJ Agarwal, N Higano, CS Vogelzang, NJ Thompson, IM AF Quinn, David I. Tangen, Catherine M. Hussain, Maha Lara, Primo N., Jr. Goldkorn, Amir Moinpour, Carol M. Garzotto, Mark G. Mack, Philip C. Carducci, Michael A. Monk, J. Paul Twardowski, Przemyslaw W. Van Veldhuizen, Peter J. Agarwal, Neeraj Higano, Celestia S. Vogelzang, Nicholas J. Thompson, Ian M., Jr. TI Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID BONE METASTASES; DOUBLE-BLIND; III TRIAL; COMPARING DOCETAXEL; ENDOTHELIN RECEPTOR; INCREASED SURVIVAL; PLUS PREDNISONE; PAIN; CHEMOTHERAPY; MITOXANTRONE AB Background The endothelin pathway has a role in bone metastases, which are characteristic of advanced prostate cancer. Atrasentan, an endothelin receptor antagonist, has shown activity in prostate cancer. We therefore assessed its effect on survival in patients with castration-resistant prostate cancer with bone metastases. Methods In a double-blind phase 3 trial, men with metastatic castration-resistant prostate cancer, stratified for progression type (prostate-specific antigen or radiological), baseline pain, extraskeletal metastases, and bisphosphonate use, were randomly assigned in a 1:1 ratio to docetaxel (75 mg/m(2) every 21 days, intravenously) with atrasentan (10 mg/day, orally) or placebo for up to 12 cycles and treated until disease progression or unacceptable toxicity. Patients who did not progress on treatment were permitted to continue atrasentan or placebo for up to 52 weeks. Coprimary endpoints were progression-free survival (PFS) and overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00134056. Findings 498 patients were randomly assigned to the atrasentan group and 496 to the placebo group. The trial was halted early for futility in April, 2011, after a planned interim analysis. Median PFS was 9.2 months (95% CI 8.5-9.9) in the atrasentan group and 9.1 months (8.4-10.2) in the placebo group (hazard ratio 1.02, 0.89-1.16; p=0.81). Median overall survival was 17.8 months (16.4-19.8) in the atrasentan group versus 17.6 months (16.4-20.1) in the placebo group (1.04, 0.90-1.19; p=0.64). 278 (57%) of 492 patients in the atrasentan group had grade 3 and greater toxicity compared with 294 (60%) of 486 in the placebo group (p=0.22). Three deaths in the atrasentan group and seven in the placebo group were judged to be possibly or probably due to protocol treatment. Interpretation Atrasentan, when added to docetaxel, does not improve overall survival or PFS in men with castration-resistant prostate cancer and bone metastases; therefore, single-agent docetaxel should remain as one of the standard treatments. C1 [Quinn, David I.; Goldkorn, Amir] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Tangen, Catherine M.; Moinpour, Carol M.] SWOG Stat Ctr, Seattle, WA USA. [Hussain, Maha] Univ Michigan, Ann Arbor, MI 48109 USA. [Lara, Primo N., Jr.; Mack, Philip C.] Univ Calif Davis, Sacramento, CA 95817 USA. [Garzotto, Mark G.] Portland VA Med Ctr, Portland, OR USA. [Carducci, Michael A.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Monk, J. Paul] Ohio State Univ, Columbus, OH 43210 USA. [Twardowski, Przemyslaw W.] City Hope Natl Med Ctr, Med Ctr, Duarte, CA USA. [Van Veldhuizen, Peter J.] Univ Kansas, Kansas City, KS USA. [Agarwal, Neeraj] Univ Utah, Salt Lake City, UT USA. [Higano, Celestia S.] Seattle Canc Care Alliance, Puget Sound Oncol Consortium, Seattle, WA USA. [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Vogelzang, Nicholas J.] US Oncol Res, Ctr Comprehens Canc, Las Vegas, NV USA. [Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Quinn, DI (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, 1441 Eastlake Ave,Suite 3440, Los Angeles, CA 90033 USA. EM diquinn@med.usc.edu RI Quinn, David/F-4343-2015 OI Quinn, David/0000-0002-1411-0417 FU Public Health Service; National Cancer Institute, Department of Health and Human Services [CA32102, CA38926, CA46368, CA46441, CA58882, CA58861, CA12644, CA22433, CA46282, CA27057, CA58416, CA45807, CA45808, CA45450, CA42777, CA35281, CA20319, CA35090, CA76429, CA14028, CA67575, CA45377, CA68183, CA63848, CA74647, CA16385, CA35192, CA63844, CA11083, CA63845, CA76447]; Sanofi-Aventis; Abbott Laboratories FX The investigation was supported, partly, by the following Public Health Service Cooperative Agreement grant numbers awarded by the National Cancer Institute, Department of Health and Human Services: CA32102, CA38926, CA46368, CA46441, CA58882, CA58861, CA12644, CA22433, CA46282, CA27057, CA58416, CA45807, CA45808, CA45450, CA42777, CA35281, CA20319, CA35090, CA76429, CA14028, CA67575, CA45377, CA68183, CA63848, CA74647, CA16385, CA35192, CA63844, CA11083, CA63845, CA76447, CA35128, CA13612, CA35431, CA76448, CA35178, CA35176, CA35119, CA35421, CA128567, CA04919, CA68183, CA45560, CA37981, CA58723, CA21115, CA16116, and CA31949; and, partly, by Sanofi-Aventis and Abbott Laboratories. The authors report on behalf of a large team and would like to acknowledge the contribution of clinicians, research teams, patients, and their families through ECOG, CALGB, and the Clinical Trials Support Unit in completing SWOG S0421. NR 33 TC 58 Z9 64 U1 0 U2 3 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 AUG PY 2013 VL 14 IS 9 BP 893 EP 900 DI 10.1016/S1470-2045(13)70294-8 PG 8 WC Oncology SC Oncology GA 205DZ UT WOS:000323423400046 PM 23871417 ER PT J AU Chawla, S Henshaw, R Seeger, L Choy, E Blay, JY Ferrari, S Kroep, J Grimer, R Reichardt, P Rutkowski, P Schuetze, S Skubitz, K Staddon, A Thomas, D Qian, Y Jacobs, I AF Chawla, Sant Henshaw, Robert Seeger, Leanne Choy, Edwin Blay, Jean-Yves Ferrari, Stefano Kroep, Judith Grimer, Robert Reichardt, Peter Rutkowski, Piotr Schuetze, Scott Skubitz, Keith Staddon, Arthur Thomas, David Qian, Yi Jacobs, Ira TI Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study SO LANCET ONCOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; OSTEOCLAST PRECURSORS; RECEPTOR ACTIVATOR; ZOLEDRONIC ACID; GENE-EXPRESSION; KAPPA-B; CRITERIA; CANCER; LIGAND AB Background Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB. Methods We did an international, open-label, parallel-group, phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease. Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg. We divided patients into three cohorts-those with surgically unsalvageable GCTB (cohort 1), those with salvageable GCTB whose surgery was associated with severe morbidity (cohort 2), and those who transferred from a previous study of denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. Investigator-determined disease status and clinical benefit were assessed every 4 weeks. Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities. Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2. Safety analyses included all patients who received at least one dose of denosumab. Efficacy analyses included all eligible patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, identifier NCT00680992. Findings 282 patients, including ten adolescents, were included between Sept 9, 2008, and March 25, 2011. Of the 281 patients analysable for safety, three (1%) had osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3-4 adverse events were hypophosphataemia, which occurred in nine (3%) patients, and anaemia, back pain, and pain in extremities, each of which occurred in three patients (1%). Serious adverse events were reported in 25 (9%) patients. No treatment-related deaths were reported. On the basis of investigators' assessment of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months (IQR 5.8-21.0). In cohort 2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients who had surgery underwent a less morbid procedure than planned. Median follow-up in cohort 2 was 9.2 months (IQR 4.2-12.9). Interpretation Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB. C1 [Chawla, Sant] Sarcoma Oncol Ctr, Santa Monica, CA 90403 USA. [Henshaw, Robert] Georgetown Univ, Washington Canc Inst, Medstar Washington Hosp Ctr, Washington, DC USA. [Seeger, Leanne] UCLA Hlth Syst, Musculoskeletal Imaging, Los Angeles, CA USA. [Choy, Edwin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blay, Jean-Yves] Univ Lyon 1, F-69365 Lyon, France. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. [Ferrari, Stefano] Ist Ortoped Rizzoli, Bologna, Italy. [Kroep, Judith] Leiden Univ, Med Ctr, Leiden, Netherlands. [Grimer, Robert] Royal Orthopaed Hosp, Birmingham B31 2AP, W Midlands, England. [Reichardt, Peter] HELIOS Klinikum Berlin Buch, Berlin, Germany. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, Piotr] Inst Oncol, Warsaw, Poland. [Schuetze, Scott] Univ Michigan, Ann Arbor, MI 48109 USA. [Skubitz, Keith] Univ Minnesota, Minneapolis, MN USA. [Staddon, Arthur] Penn Oncol Hematol Associates, Philadelphia, PA USA. [Thomas, David] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Qian, Yi; Jacobs, Ira] Amgen Inc, Thousand Oaks, CA USA. RP Chawla, S (reprint author), Sarcoma Oncol Ctr, 2811 Wilshire Blvd,Suite 414, Santa Monica, CA 90403 USA. EM santchawla@sarcomaoncology.com RI Blay, Jean-Yves/N-3966-2016; OI Blay, Jean-Yves/0000-0001-7190-120X; Choy, Edwin/0000-0001-9896-8084; Rutkowski, Piotr/0000-0002-8920-5429 FU Amgen FX This study was funded by Amgen. We thank Ada Braun for writing contributions, data interpretation, and critical review, and Lori Gorton for providing medical writing, editing, and formatting assistance. NR 25 TC 99 Z9 100 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2013 VL 14 IS 9 BP 901 EP 908 DI 10.1016/S1470-2045(13)70277-8 PG 8 WC Oncology SC Oncology GA 205DZ UT WOS:000323423400047 PM 23867211 ER PT J AU Chavarri-Guerra, Y Sullivan, R Goss, PE AF Chavarri-Guerra, Yanin Sullivan, Richard Goss, Paul E. TI Cancer control in Chile Reply SO LANCET ONCOLOGY LA English DT Letter C1 [Chavarri-Guerra, Yanin] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Hematol Oncol, Salvador Zubiran, Mexico. [Sullivan, Richard] Kings Coll London, Kings Hlth Partners, Integrated Canc Ctr, Guys Hosp, London WC2R 2LS, England. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Canc Ctr Excellence, Avon Breast, Boston, MA 02114 USA. RP Chavarri-Guerra, Y (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Hematol Oncol, Salvador Zubiran, Mexico. EM pgoss@partners.org NR 4 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 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2013 VL 14 IS 9 BP E338 EP E338 PG 1 WC Oncology SC Oncology GA 205DZ UT WOS:000323423400003 PM 23896269 ER PT J AU Lapierre, LR De Magalhaes, CD McQuary, PR Chu, CC Visvikis, O Chang, JT Gelino, S Ong, B Davis, AE Irazoqui, JE Dillin, A Hansen, M AF Lapierre, Louis R. De Magalhaes Filho, C. Daniel McQuary, Philip R. Chu, Chu-Chiao Visvikis, Orane Chang, Jessica T. Gelino, Sara Ong, Binnan Davis, Andrew E. Irazoqui, Javier E. Dillin, Andrew Hansen, Malene TI The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans SO NATURE COMMUNICATIONS LA English DT Article ID LIFE-SPAN EXTENSION; MESSENGER-RNA TRANSLATION; C-ELEGANS; DIETARY RESTRICTION; TRANSCRIPTION FACTORS; LYSOSOMAL BIOGENESIS; LIPID-METABOLISM; GENES; GENETICS; CONSUMPTION AB Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination. We demonstrate that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan. Nuclear localization of HLH-30 is increased in all six Caenorhabditis elegans models and, notably, nuclear TFEB levels are augmented in the livers of mice subjected to dietary restriction, a known longevity-extending regimen. Collectively, our results demonstrate a conserved role for HLH-30 and TFEB in autophagy, and possibly longevity, and identify HLH-30 as a uniquely important transcription factor for lifespan modulation in Caenorhabditis elegans. C1 [Lapierre, Louis R.; McQuary, Philip R.; Chu, Chu-Chiao; Chang, Jessica T.; Gelino, Sara; Ong, Binnan; Davis, Andrew E.; Hansen, Malene] Sanford Burnham Med Res Inst, Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA. [De Magalhaes Filho, C. Daniel; Dillin, Andrew] Salk Inst Biol Studies, Howard Hughes Med Inst, Glenn Ctr Aging Res, La Jolla, CA 92037 USA. [McQuary, Philip R.; Gelino, Sara] Sanford Burnham Med Res Inst, Grad Sch Biomed Sci, La Jolla, CA USA. [Visvikis, Orane; Irazoqui, Javier E.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hansen, M (reprint author), Sanford Burnham Med Res Inst, Aging & Stem Cell Res Ctr, Program Dev & Aging, 10901 N Torrey Pines Rd, La Jolla, CA USA. EM mhansen@sanfordburnham.org RI di Ronza, Alberto/H-7674-2016; VISVIKIS, ORANE/N-1818-2016; OI di Ronza, Alberto/0000-0002-9813-5143; VISVIKIS, ORANE/0000-0001-7719-5836; Lapierre, Louis/0000-0002-8154-141X; Irazoqui, Javier/0000-0001-6553-1329 FU NIH/UCSD [P50 AG005131-29]; Glenn Foundation for Aging Research fellowship; Fund for Medical Discovery postdoctoral fellowship from the Massachusetts General Hospital; NIH/NIA [F31 AG039222, R01 AG027463, R01 AG038664, R01 AG039756]; NIH/NIGMS [R01 GM101056] FX We thank all Hansen lab members for helpful discussions, and Drs H. Aguilaniu, A. Ghazi, C. Kumsta, A. O'Rourke, E. Troemel and D. Wilkinson for comments on the manuscript. We thank the Mitani lab for the hlh-30(tm1978) strain. L.R.L. was funded by the NIH/UCSD (P50 AG005131-29), C.D.D.M.F. by a Glenn Foundation for Aging Research fellowship, O.V. by a Fund for Medical Discovery postdoctoral fellowship from the Massachusetts General Hospital, P.R.M. by NIH/NIA (F31 AG039222), J.E.I. by NIH/NIGMS (R01 GM101056), A.D. by NIH/NIA (R01 AG027463) and M.H. by NIH/NIA (R01 AG038664 and R01 AG039756). NR 40 TC 64 Z9 65 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD AUG PY 2013 VL 4 AR 2267 DI 10.1038/ncomms3267 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209JG UT WOS:000323751200007 PM 23925298 ER PT J AU Hoppe, BS Hodgson, DC Advani, R Dabaja, BS Flowers, CR Ha, CS Metzger, ML Plastaras, JP Roberts, KB Shapiro, R Terezakis, SA Winkfield, KM Younes, A Constine, LS AF Hoppe, Bradford S. Hodgson, David C. Advani, Ranjana Dabaja, Bouthaina S. Flowers, Christopher R. Ha, Chul S. Metzger, Monika L. Plastaras, John P. Roberts, Kenneth B. Shapiro, Ronald Terezakis, Stephanie A. Winkfield, Karen M. Younes, Anas Constine, Louis S. TI ACR APPROPRIATENESS CRITERIA (R) Localized Nodal Indolent Lymphoma SO ONCOLOGY-NEW YORK LA English DT Review ID NON-HODGKINS-LYMPHOMA; INTERNATIONAL PROGNOSTIC INDEX; TERM-FOLLOW-UP; INVOLVED-FIELD RADIOTHERAPY; FOLLICULAR LYMPHOMA; LOW-GRADE; STAGE-I; NATIONAL LYMPHOCARE; RADIATION-THERAPY; UNITED-STATES AB The present guidelines review epidemiology, pathology, presentation, workup, staging, prognostic factors, and treatment options for patients with localized nodal indolent lymphoma, with an emphasis on radiation guidelines, including radiation dose, field design, and radiation techniques. Following a discussion of the current literature and available data for treatment and outcomes of patients with indolent lymphoma, several different example cases are reviewed to help. physicians make appropriate treatment decisions. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) by which the panel rates the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Hoppe, Bradford S.] Univ Florida, Proton Therapy Inst, Jacksonville, FL 32209 USA. [Hodgson, David C.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Advani, Ranjana] Stanford Canc Ctr, Stanford, CA USA. [Dabaja, Bouthaina S.; Younes, Anas] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Flowers, Christopher R.] Emory Univ, Atlanta, GA 30322 USA. [Ha, Chul S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Metzger, Monika L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Plastaras, John P.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Roberts, Kenneth B.] Yale Univ, Sch Med, New Haven, CT USA. [Shapiro, Ronald] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Terezakis, Stephanie A.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Winkfield, Karen M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Constine, Louis S.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Hoppe, BS (reprint author), Univ Florida, Proton Therapy Inst, Jacksonville, FL 32209 USA. RI Flowers, Christopher/F-1953-2010; OI Flowers, Christopher/0000-0002-9524-3990; Terezakis, Stephanie/0000-0003-4933-6712; Hoppe, Bradford/0000-0002-2312-5418 FU Novartis; Johnson Johnson; Seattle Genetics; Merck; Genentech; Infinity; Gilead FX Christopher R. Flowers, MD, MS reports: "I provide consultation for the Prescription Solutions Pharmacy & Therapeutics Division. My consultation involves advice on FDA regulated drugs only. None of my consultation overlaps with existing or planned ACR guidelines." Anas Younes, MD, reports: "Honoraria from Novartis, Seattle Genetics, Millennium, Celgene, Curis, Sanofi, Pharmacyclics, and Incyte; research support from Novartis, Johnson & Johnson, Seattle Genetics, Merck, Genentech, Infinity, and Gilead." NR 46 TC 3 Z9 3 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD AUG PY 2013 VL 27 IS 8 BP 786 EP 794 PG 9 WC Oncology SC Oncology GA 208NM UT WOS:000323686400009 PM 24133827 ER PT J AU Richardson, PG Laubach, J Paba-Prada, C Anderson, KC AF Richardson, Paul G. Laubach, Jacob Paba-Prada, Claudia Anderson, Kenneth C. TI IgD and IgE Variants of Myeloma: Valuable Insights and Therapeutic Opportunities THE PANDEY/KYLE ARTICLE REVIEWED SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID MULTIPLE-MYELOMA; EXTRAMEDULLARY DISEASE; PRESENTING FEATURES; TRANSPLANTATION; AMYLOIDOSIS; SURVIVAL C1 [Richardson, Paul G.; Laubach, Jacob; Paba-Prada, Claudia; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancies, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancies, Boston, MA 02115 USA. NR 22 TC 2 Z9 2 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD AUG PY 2013 VL 27 IS 8 BP 803 EP + PG 3 WC Oncology SC Oncology GA 208NM UT WOS:000323686400012 PM 24133830 ER PT J AU Schulz, CF Davis, TT Fung, DA AF Schulz, Carolyn F. Davis, Timothy T. Fung, Daniel A. TI Epidural Lipomatosis as a Cause for High Impedance Values During a Spinal Cord Stimulator Trial SO PM&R LA English DT Article ID MECHANISMS C1 [Schulz, Carolyn F.] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA USA. [Davis, Timothy T.; Fung, Daniel A.] Ctr Spine & Joint Restorat, Santa Monica, CA 90043 USA. RP Fung, DA (reprint author), Ctr Spine & Joint Restorat, 2811 Wilshire Blvd,Suite 850, Santa Monica, CA 90043 USA. EM DFUNGMD@gmail.com FU Medtronic FX Disclosures outside this publication: board membership (no money), ABNM; consultancy, Medtronic; payment for lectures including service on speakers bureaus, Medtronic; payment for development of educational presentations, Medtronic; travel/accommodations/meeting expenses, Medtronic NR 9 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD AUG PY 2013 VL 5 IS 8 BP 729 EP 731 DI 10.1016/j.pmrj.2013.04.021 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 207JK UT WOS:000323594500019 PM 23643840 ER PT J AU DeLelys, ME Ochoa, G Cserti-Gazdewich, CM Vietz, C Preffer, FI Dzik, W AF DeLelys, Michelle E. Ochoa, Gorka Cserti-Gazdewich, Christine M. Vietz, Christine Preffer, Frederic I. Dzik, Walter TI Relationship between ABO genotype and A antigen expression on platelets SO TRANSFUSION LA English DT Article ID BLOOD-GROUP-A; TRANSFUSION; INCREMENTS; INDIVIDUALS; DELETION; ALLELES; DISEASE AB BACKGROUND: Although platelets (PLTs) are known to express ABH antigens, the extent of expression is different on PLTs compared with red blood cells and the relationship between PLT ABH expression and genotype has not been thoroughly investigated. STUDY DESIGN AND METHODS: We measured blood group H and A antigens on PLTs from 100 normal volunteers using fluorescent-conjugated reagents and flow cytometry. Individuals were also genotyped at the ABO locus using a commercially available genotyping system. RESULTS: Expression of A and H antigen varied widely on PLTs from different individuals. Among group A and AB persons, H antigen expression was significantly greater than A antigen (p<0.0001). The ratio of H-to-A antigen expression varied more than 100-fold in a predictable fashion according to genotype with values lowest in A(1)/A(1)18 years) ED visits resulting in discharge in 2007. Candidate predictors included index hospital structural characteristics such as ownership, teaching affiliation, trauma status, and index ED size, along with index visit patient characteristics of demographic information, day of service, against medical advice or eloped disposition, insurance, and ED primary discharge diagnosis. We fit a nnultivariable, hierarchic logistic regression to account for clustering of ED visits by hospitals. Results: The study cohort contained a total of 5,035,833 visits to 288 facilities in 2007. Bounce-back admission within 7 days occurred in 130,526 (2.6%) visits and was associated with Medicaid (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.40 to 1.45) or Medicare insurance (OR 1.53; 95% CI 1.50 to 1.55) and a disposition of leaving against medical advice or before the evaluation was complete (OR 1.90; 95% CI 1.89 to 2.0). The 3 most common age-adjusted index ED discharge diagnoses associated with a bounce-back admission were chronic renal disease, not end stage (OR 3.3; 95% CI 2.8 to 3.8), end-stage renal disease (OR 2.9; 95% CI 2.4 to 3.6), and congestive heart failure (OR 2.5; 95% CI 2.3 to 2.6). Hospital characteristics associated with a higher bounce-back admission rate were for-profit status (OR 1.2; 95% CI 1.1 to 1.3) and teaching affiliation (OR 1.2; 95% CI 1.0 to 1.3). Conclusion: We found 2.6% of discharged patients from California EDs to have a bounce-back admission within 7 days. We identified vulnerable populations, such as the very old and the use of Medicaid insurance, and chronic or end-stage renal disease as being especially at risk. Our findings suggest that quality improvement efforts focus on high-risk individuals and that the disposition plan of patients consider vulnerable populations. C1 [Gabayan, Gelareh Z.; Zingmond, David; Liang, Li-Jung] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.] Greater Los Angeles Vet Affairs Healthcare Syst, Div Emergency Med, Los Angeles, CA USA. [Gabayan, Gelareh Z.] Ronald Reagan UCLA, Ctr Emergency Med, Los Angeles, CA USA. [Asch, Steven M.] Vet Affairs Palo Alto Healthcare Syst, Div Gen Med Disciplines, Palo Alto, CA USA. [Asch, Steven M.] Stanford Sch Med, Palo Alto, CA USA. [Hsia, Renee Y.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Han, Weijuan; McCreath, Heather; Weiss, Robert E.] UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. RP Gabayan, GZ (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. EM gelareh@gabayan.com FU Emergency Medicine Foundation; Agency for Healthcare Research and Quality [R03 HS18098]; UCLA Older American Independence Center NIH/National Institute on Aging (NIA) grant; NIH/NCRR/OD UCSF-CTSI grant [KL2RR024130]; Robert Wood Johnson Foundation Physician Faculty Scholars; NIH/NCRR/NCATS UCLA CTSI [KL2TR000122] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. This research was supported by the Emergency Medicine Foundation (Dr. Sun), the Agency for Healthcare Research and Quality (Dr. Sun, R03 HS18098), the UCLA Older American Independence Center NIH/National Institute on Aging (NIA) grant (Dr. McCreath, Mrs. Han), the NIH/NCRR/OD UCSF-CTSI grant (Dr. Hsia, KL2RR024130), and the Robert Wood Johnson Foundation Physician Faculty Scholars (Dr. Hsia). Dr. Gabayan receives support from the NIH/NCRR/NCATS UCLA CTSI (grant KL2TR000122). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the NIA. The funding organizations did not have a role in the design and conduct of the study; management, analysis, and interpretation of the data; and preparation, review, or approval of the article. NR 42 TC 12 Z9 12 U1 0 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2013 VL 62 IS 2 BP 136 EP 144 DI 10.1016/j.annemergmed.2013.01.017 PG 9 WC Emergency Medicine SC Emergency Medicine GA 199SC UT WOS:000323014800008 PM 23465554 ER PT J AU Doran, KM Raven, MC Rosenheck, RA AF Doran, Kelly M. Raven, Maria C. Rosenheck, Robert A. TI What Drives Frequent Emergency Department Use in an Integrated Health System? National Data From the Veterans Health Administration SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID UTILIZATION PATTERNS; MENTAL-DISORDERS; RANDOMIZED-TRIAL; CASE-MANAGEMENT; MEDICAL-CARE; RISK-FACTORS; SERVICES; OUTCOMES; DEFINITIONS; POPULATION AB Study objective: There is widespread concern about patients with frequent emergency department (ED) use. We identify sociodemographic and clinical factors most strongly associated with frequent ED use within the Veterans Health Administration (VHA) nationally. Methods: We conducted a cross-sectional analysis of national VHA databases (N=5,531,379) in 2010. The primary outcome measure was the number of VHA ED visits categorized into 6 frequency levels. Results: In 2010, 4,600,667 (83.2%) VHA patients had no ED visit, whereas 493,391 (8.9%) had 1 visit, 356,258 (6.4%) had 2 to 4 visits, 70,741 (1.3%) had 5 to 10 visits, 9,705 (0.2%) had 11 to 25 visits, and 617 (0.01%) had greater than 25 visits. Increasing ED use frequency was associated with homelessness, medical diagnoses, substance abuse and psychiatric diagnoses, receipt of psychotropic and opioid prescriptions, and more frequent use of outpatient medical and mental health services. In multivariable analyses, factors most strongly associated with all levels of ED use were schizophrenia (odds ratio [OR] range 1.44 [95% confidence interval {Cl} 1.41 to 1.47] to 6.86 [95% Cl 5.55 to 8.48] across categories of increasing ED use), homelessness (OR range 1.41 [95% CI 1.38 to 1.43] to 6.60 [95% Cl 5.36 to 8.12]), opioid prescriptions filled (OR range 2.09 [95% Cl 2.07 to 2.10] to 5.08 [95% Cl 4.16 to 6.19]), and heart failure (OR range 1.64 [95% Cl 1.63 to 1.66] to 3.53 [95% Cl 2.64 to 4.72]). Conclusion: Frequent ED use occurs even in a coordinated health care system that provides ready access to outpatient care. Frequent ED users are characterized by traits that represent high levels of psychosocial and medical needs. The correlates we identified for frequent ED use were consistent across multiple distinct levels of ED use. C1 [Doran, Kelly M.] Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. [Doran, Kelly M.] US Dept Vet Affairs, New Haven, CT USA. [Doran, Kelly M.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Raven, Maria C.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Rosenheck, Robert A.] VA New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. RP Doran, KM (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. EM kelly.doran@yale.edu FU VA New England Mental Illness Research and Education Center FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. Support was provided by the VA New England Mental Illness Research and Education Center. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and the preparation, review, or approval of the article. NR 44 TC 35 Z9 35 U1 2 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2013 VL 62 IS 2 BP 151 EP 159 DI 10.1016/j.annemergmed.2013.02.016 PG 9 WC Emergency Medicine SC Emergency Medicine GA 199SC UT WOS:000323014800011 PM 23582617 ER PT J AU Dutta, S Long, WJ Brown, DFM Reisner, AT AF Dutta, Sayon Long, William J. Brown, David F. M. Reisner, Andrew T. TI Automated Detection Using Natural Language Processing of Radiologists Recommendations for Additional Imaging of Incidental Findings SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys ID PREVALENCE; RECORDS; CANCER; SCANS AB Study objective: As use of radiology studies increases, there is a concurrent increase in incidental findings (eg, lung nodules) for which the radiologist issues recommendations for additional imaging for follow-up. Busy emergency physicians may be challenged to carefully communicate recommendations for additional imaging not relevant to the patient's primary evaluation. The emergence of electronic health records and natural language processing algorithms may help address this quality gap. We seek to describe recommendations for additional imaging from our institution and develop and validate an automated natural language processing algorithm to reliably identify recommendations for additional imaging. Methods: We developed a natural language processing algorithm to detect recommendations for additional imaging, using 3 iterative cycles of training and validation. The third cycle used 3,235 radiology reports (1,600 for algorithm training and 1,635 for validation) of discharged emergency department (ED) patients from which we determined the incidence of discharge-relevant recommendations for additional imaging and the frequency of appropriate discharge documentation. The test characteristics of the 3 natural language processing algorithm iterations were compared, using blinded chart review as the criterion standard. Results: Discharge-relevant recommendations for additional imaging were found in 4.5% (95% confidence interval [Cl] 3.5% to 5.5%) of ED radiology reports, but 51% (95% Cl 43% to 59%) of discharge instructions failed to note those findings. The final natural language processing algorithm had 89% (95% Cl 82% to 94%) sensitivity and 98% (95% Cl 97% to 98%) specificity for detecting recommendations for additional imaging. For discharge-relevant recommendations for additional imaging, sensitivity improved to 97% (95% Cl 89% to 100%). Conclusion: Recommendations for additional imaging are common, and failure to document relevant recommendations for additional imaging in ED discharge instructions occurs frequently. The natural language processing algorithm's performance improved with each iteration and offers a promising error-prevention tool. C1 [Dutta, Sayon; Brown, David F. M.; Reisner, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Long, William J.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Dutta, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. EM sdutta1@partners.org NR 29 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2013 VL 62 IS 2 BP 162 EP 169 DI 10.1016/j.annemergmed.2013.02.001 PG 8 WC Emergency Medicine SC Emergency Medicine GA 199SC UT WOS:000323014800013 PM 23548405 ER PT J AU Bekris, LM Lutz, F Montine, TJ Yu, CE Tsuang, D Peskind, ER Leverenz, JB AF Bekris, Lynn M. Lutz, Franziska Montine, Thomas J. Yu, Chang En Tsuang, Debby Peskind, Elaine R. Leverenz, James B. TI MicroRNA in Alzheimer's disease: an exploratory study in brain, cerebrospinal fluid and plasma SO BIOMARKERS LA English DT Article DE Amyloid; biomarker; braak stage; miR-15a; miR-370; miR-328; miR-138; miR-132; plaque ID ENDOGENOUS CONTROL GENES; NEUROPATHOLOGIC ASSESSMENT; PROSTATE-CANCER; NEURONAL LOSS; EXPRESSION; IDENTIFICATION; DEMENTIA; MIRNA; BIOMARKERS; DIAGNOSIS AB MicroRNA (miRNA) may be potential biomarkers of Alzheimer's disease (AD). The objective of this investigation was to demonstrate that miRNAs in human brain or biofluids are differentially expressed according to disease status, tissue type, neuritic plaque score or Braak stage. Post-mortem brain (PMB) miRNA were profiled using arrays and validated using quantitative RT-PCR (qRT-PCR). Five gRT-PCR-validated miRNAs were measured in an independent sample of PMB, cerebrospinal fluid and plasma from the same subjects. Plasma miR-15a was found to be associated with plaque score in the independent sample. In conclusion, miRNA present in human biofluids may offer utility as biomarkers of AD. C1 [Bekris, Lynn M.; Lutz, Franziska; Yu, Chang En; Tsuang, Debby; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Geriatr GRECC, Res Ctr, Seattle, WA USA. [Bekris, Lynn M.; Lutz, Franziska; Yu, Chang En; Tsuang, Debby; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Geriatr GRECC, Educ Ctr, Seattle, WA USA. [Bekris, Lynn M.; Lutz, Franziska; Yu, Chang En; Tsuang, Debby; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Geriatr GRECC, Ctr Clin, Seattle, WA USA. [Bekris, Lynn M.; Lutz, Franziska; Yu, Chang En] Univ Washington, Dept Med, Seattle, WA 98108 USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98108 USA. [Tsuang, Debby; Peskind, Elaine R.; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Mental Illness MIRECC, Res Ctr, Seattle, WA USA. [Tsuang, Debby; Peskind, Elaine R.; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Mental Illness MIRECC, Educ Ctr, Seattle, WA USA. [Tsuang, Debby; Peskind, Elaine R.; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Mental Illness MIRECC, Ctr Clin, Seattle, WA USA. [Tsuang, Debby; Peskind, Elaine R.; Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Parkinsons Dis PADRECC, Res Ctr, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Parkinsons Dis PADRECC, Educ Ctr, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Dept Parkinsons Dis PADRECC, Ctr Clin, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98108 USA. RP Bekris, LM (reprint author), Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Box 358280 VAPSHCS GRECC S182,1660 South Columbia, Seattle, WA 98108 USA. EM lbekris@uw.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU U.S. Department of Veterans Affairs, Office of Research and Development Clinical Research and Development Program; Biomedical Laboratory Research Program; NIH [P50AG005136-27, P50NS062684-01A1, P50 NS062684, K99AG034214-02/R00AG034214-03] FX This work is supported, in part, by the U.S. Department of Veterans Affairs, Office of Research and Development Clinical Research and Development Program, the Biomedical Laboratory Research Program and NIH Grants: P50AG005136-27, P50NS062684-01A1, P50 NS062684 and K99AG034214-02/R00AG034214-03. NR 79 TC 31 Z9 34 U1 0 U2 36 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD AUG PY 2013 VL 18 IS 5 BP 455 EP 466 DI 10.3109/1354750X.2013.814073 PG 12 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 200RF UT WOS:000323085900012 PM 23822153 ER PT J AU Tracy, MS Rosenberg, SM Dominici, L Partridge, AH AF Tracy, Michaela S. Rosenberg, Shoshana M. Dominici, Laura Partridge, Ann H. TI Contralateral prophylactic mastectomy in women with breast cancer: trends, predictors, and areas for future research SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Contralateral prophylactic mastectomy; Breast cancer; Surgery ID QUALITY-OF-LIFE; YOUNG-WOMEN; TUMOR CHARACTERISTICS; GERMLINE MUTATIONS; FAMILY-HISTORY; DECISION AID; SURVIVAL; RISK; EFFICACY; RECONSTRUCTION AB Recent studies have revealed increasing rates of contralateral prophylactic mastectomy (CPM) among women with unilateral early stage breast cancer. This trend has raised concerns, given the lack of evidence for a survival benefit from CPM and the relatively low risk of contralateral breast cancer for most women in this setting. In this article, we review available data regarding the value of CPM, predictors, and outcomes related to CPM, and areas for future research and potential intervention. C1 [Tracy, Michaela S.; Rosenberg, Shoshana M.; Dominici, Laura; Partridge, Ann H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Partridge, AH (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 450 Brookline Ave Boston, Boston, MA 02215 USA. EM ahpartridge@partners.org FU National Cancer Institute [NIH 5 R25 CA057711] FX Dr. Rosenberg receives funding from the National Cancer Institute (NIH 5 R25 CA057711). NR 46 TC 20 Z9 20 U1 2 U2 10 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 AUG PY 2013 VL 140 IS 3 BP 447 EP 452 DI 10.1007/s10549-013-2643-6 PG 6 WC Oncology SC Oncology GA 202UP UT WOS:000323245400002 PM 23893127 ER PT J AU Specht, MC Miller, CL Russell, TA Horick, N Skolny, MN O'Toole, JA Jammallo, LS Niemierko, A Sadek, BT Shenouda, MN Finkelstein, DM Smith, BL Taghian, AG AF Specht, Michelle C. Miller, Cynthia L. Russell, Tara A. Horick, Nora Skolny, Melissa N. O'Toole, Jean A. Jammallo, Lauren S. Niemierko, Andrzej Sadek, Betro T. Shenouda, Mina N. Finkelstein, Dianne M. Smith, Barbara L. Taghian, Alphonse G. TI Defining a threshold for intervention in breast cancer-related lymphedema: what level of arm volume increase predicts progression? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Lymphedema; Quality of life; Compression therapy; Threshold for intervention; Early intervention ID SENTINEL NODE BIOPSY; RISK-FACTORS; FOLLOW-UP; AXILLARY DISSECTION; CONSERVING THERAPY; EARLY-DIAGNOSIS; LIMB VOLUME; GROUP TRIAL; SURVIVORS; SURGERY AB The purpose of this study is to evaluate arm volume measurements and clinico-pathologic characteristics of breast cancer patients to define a threshold for intervention in breast cancer-related lymphedema. We prospectively performed arm volume measurements on breast cancer patients using a Perometer. Arm measurements were performed pre- and post-operatively, and change in arm volume was quantified using a relative volume change (RVC) equation. Patient and treatment risk factors were evaluated. Cox proportional hazards models with time-dependent covariates for RVC were used to evaluate whether RVC elevations of a parts per thousand yen3 to < 5 % or a parts per thousand yen5 to < 10 % occurring a parts per thousand currency sign3 months or > 3 months after surgery were associated with progression to a parts per thousand yen10 % RVC. 1,173 patients met eligibility criteria with a median of 27 months post-operative follow-up. The cumulative incidence of a parts per thousand yen10 % RVC at 24 months was 5.26 % (95 % CI 4.01-6.88 %). By multivariable analysis, a measurement of a parts per thousand yen5 to < 10 % RVC occurring > 3 months after surgery was significantly associated with an increased risk of progression to a parts per thousand yen10 % RVC (HR 2.97, p < 0.0001), but a measurement of a parts per thousand yen3 to < 5 % RVC during the same time period was not statistically significantly associated (HR 1.55, p = 0.10). Other significant risk factors included a measurement a parts per thousand currency sign3 months after surgery with RVC of a parts per thousand yen3 to < 5 % (p = 0.007), a parts per thousand yen5 to < 10 % (p < 0.0001), or a parts per thousand yen10 % (p = 0.023), axillary lymph node dissection (ALND) (p < 0.0001), and higher BMI at diagnosis (p = 0.0028). Type of breast surgery, age, number of positive or number of lymph nodes removed, nodal radiation, chemotherapy, and hormonal therapy were not significant (p > 0.05). Breast cancer patients who experience a relative arm volume increase of a parts per thousand yen3 to < 5 % occurring > 3 months after surgery do not have a statistically significant increase in risk of progression to a parts per thousand yen10 %, a common lymphedema criterion. Our data support utilization of a a parts per thousand yen5 to < 10 % threshold for close monitoring or intervention, warranting further assessment. Additional risk factors for progression to a parts per thousand yen10 % include ALND, higher BMI, and post-operative arm volume elevation. C1 [Specht, Michelle C.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Miller, Cynthia L.; Russell, Tara A.; Skolny, Melissa N.; Jammallo, Lauren S.; Niemierko, Andrzej; Sadek, Betro T.; Shenouda, Mina N.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Horick, Nora; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [O'Toole, Jean A.] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 FU National Cancer Institute [R01CA139118, P50CA089393] FX This project was supported by Award R01CA139118 (AGT), and Award P50CA089393 (AGT) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institutes of Health. In addition, we would like to acknowledge Nadine R. Taghian, whose dedication helped expedite completion of this project. The authors are greatly appreciative of her efforts. NR 65 TC 20 Z9 20 U1 0 U2 11 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 AUG PY 2013 VL 140 IS 3 BP 485 EP 494 DI 10.1007/s10549-013-2655-2 PG 10 WC Oncology SC Oncology GA 202UP UT WOS:000323245400006 PM 23912961 ER PT J AU Porthan, K Viitasalo, M Toivonen, L Havulinna, AS Jula, A Tikkanen, JT Vaananen, H Nieminen, MS Huikuri, HV Newton-Cheh, C Salomaa, V Oikarinen, L AF Porthan, Kimmo Viitasalo, Matti Toivonen, Lauri Havulinna, Aki S. Jula, Antti Tikkanen, Jani T. Vaeaenaenen, Heikki Nieminen, Markku S. Huikuri, Heikki V. Newton-Cheh, Christopher Salomaa, Veikko Oikarinen, Lasse TI Predictive Value of Electrocardiographic T-Wave Morphology Parameters and T-Wave Peak to T-Wave End Interval for Sudden Cardiac Death in the General Population SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE electrocardiography; epidemiology; prognosis; repolarization; sudden death ID CORONARY-HEART-DISEASE; VENTRICULAR REPOLARIZATION; CARDIOVASCULAR MORTALITY; ALL-CAUSE; QT INTERVAL; POSTMENOPAUSAL WOMEN; AMERICAN-INDIANS; RISK-FACTORS; HETEROGENEITY; MEN AB Background-Previous population studies have found an association between electrocardiographic T-wave morphology parameters and cardiovascular mortality, but their relationship to sudden cardiac death (SCD) is not clear. To our knowledge, there are no follow-up studies assessing the association between electrocardiographic T-wave peak to T-wave end interval (TPE) and SCD. We assessed the predictive value of electrocardiographic T-wave morphology parameters and TPE for SCD in an adult general population sample. Methods and Results-A total of 4 T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) as well as TPE were measured from digital standard 12-lead ECGs in 5618 adults (46% men; mean age 50.9 +/- 12.5 years) participating in the Finnish population-based Health 2000 Study. After a mean follow-up time of 7.7 +/- 1.4 years, 72 SCDs had occurred. In univariable analyses, all T-wave morphology parameters were associated with an increased SCD risk. In multivariable Cox models, T-wave morphology dispersion and total cosine R-to-T remained as predictors of SCD, with T-wave morphology dispersion showing the highest SCD risk (hazard ratio of 1.4 [95% confidence interval 1.1-1.7, P=0.001] per 1 SD increase in the log(e) T-wave morphology dispersion). In contrast, TPE was not associated with SCD in univariable or multivariable analyses. Conclusions-Electrocardiographic T-wave morphology parameters describing the 3-dimensional shape of the T-wave stratify SCD risk in the general population, but we did not find an association between TPE and SCD. C1 [Porthan, Kimmo; Viitasalo, Matti; Toivonen, Lauri; Nieminen, Markku S.; Oikarinen, Lasse] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki 00029, Finland. [Havulinna, Aki S.; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Turku, Finland. [Tikkanen, Jani T.; Huikuri, Heikki V.] Univ Oulu, Inst Clin Med, Dept Internal Med, SF-90100 Oulu, Finland. [Tikkanen, Jani T.; Huikuri, Heikki V.] Univ Cent Hosp Oulu, Oulu, Finland. [Huikuri, Heikki V.] Aalto Univ, Dept Biomed Engn & Computat Sci, Helsinki, Finland. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. RP Porthan, K (reprint author), Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Haartmaninkatu 4,POB 340, Helsinki 00029, Finland. EM kimmo.porthan@fimnet.fi FU Aarne Koskelo Foundation; Finnish Foundation for Cardiovascular Research; Finnish Medical Foundation; Orion-Farmos Research Foundation; Finnish Cultural Foundation; Academy of Finland [129494, 139635] FX Dr Porthan was supported by grants from the Aarne Koskelo Foundation, the Finnish Foundation for Cardiovascular Research, the Finnish Medical Foundation, and the Orion-Farmos Research Foundation. Drs Viitasalo, Huikuri, and Oikarinen were supported by grants from the Finnish Foundation for Cardiovascular Research. Dr Tikkanen was supported by grants from the Finnish Foundation for Cardiovascular Research, the Finnish Cultural Foundation, and the Finnish Medical Foundation. Dr Salomaa was supported by the Academy of Finland (grant numbers 129494 and 139635) and the Finnish Foundation for Cardiovascular Research. NR 37 TC 21 Z9 22 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2013 VL 6 IS 4 BP 690 EP 696 DI 10.1161/CIRCEP.113.000356 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 203WB UT WOS:000323323900016 PM 23881778 ER PT J AU Sayadi, O Merchant, FM Puppala, D Mela, T Singh, JP Heist, EK Owen, C Armoundas, AA AF Sayadi, Omid Merchant, Faisal M. Puppala, Dheeraj Mela, Theofanie Singh, Jagmeet P. Heist, E. Kevin Owen, Chris Armoundas, Antonis A. TI A Novel Method for Determining the Phase of T-Wave Alternans: Diagnostic and Therapeutic Implications SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE alternans; arrhythmia (heart rhythm disorders); defibrillators, implantable; intracardiac electrogram; pacing ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; REPOLARIZATION ALTERNANS; VENTRICULAR TACHYARRHYTHMIAS; RISK STRATIFICATION; CARDIAC ALTERNANS; FIBRILLATION; HEART; ELECTROGRAMS; TACHYCARDIA; MECHANISMS AB Background-T-wave alternans (TWA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. However, to estimate and suppress TWA effectively, the phase of TWA must be accurately determined. Methods and Results-We developed a method that computes the beat-by-beat integral of the T-wave morphology, over time points within the T-wave with positive alternans. Then, we estimated the signed derivative of the T-wave integral sequence, which allows the classification of each beat to a binary phase index. In animal studies, we found that this method was able to accurately identify the T-wave phase in artificially induced alternans (P<0.0001). The coherence of the phase increased consistently after acute ischemia induction in all body-surface and intracardiac leads (P<0.0001). Also, we developed a phase-resetting detection algorithm that enhances the diagnostic utility of TWA. We further established an algorithm that uses the phase of TWA to deliver appropriate polarity-pacing pulses (all interventions compared with baseline, P<0.0001 for alternans voltage; P<0.0001 for K-score), to suppress TWA. Finally, we demonstrated that using the phase of TWA we can suppress spontaneous TWA during acute ischemia; 77.6% for alternans voltage (P<0.0001) and 92.5% for K-score (P<0.0001). Conclusions-We developed a method to quantify the temporal variability of the TWA phase. This method is expected to enhance the utility of TWA in predicting ventricular arrhythmias and sudden cardiac death and raises the possibility of using upstream therapies to abort a ventricular tachyarrhythmia before its onset. C1 [Sayadi, Omid; Puppala, Dheeraj; Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Mela, Theofanie; Singh, Jagmeet P.; Heist, E. Kevin] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Owen, Chris] Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA. [Merchant, Faisal M.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Armoundas, Antonis A.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org FU Scientist Development Grant [0635127 N]; American Heart Association [12POST9310001]; National Institutes of Health (NIH) [1R21AG035128]; Center for Integration of Medicine and Innovative Technology (CIMIT); Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Cardiovascular Research Society; Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH) [8UL1TR000170-05]; Harvard University and its affiliated academic healthcare centers) FX The work was supported by a Scientist Development Grant (#0635127 N) and a Founders Affiliate Post-doctoral Fellowship (#12POST9310001) from the American Heart Association, and by National Institutes of Health (NIH) grant 1R21AG035128. This work was also supported by a Fellowship and a Science Award from the Center for Integration of Medicine and Innovative Technology (CIMIT), the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, and the Cardiovascular Research Society. This work was performed with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic healthcare centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the NIH. NR 29 TC 1 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2013 VL 6 IS 4 BP 818 EP 826 DI 10.1161/CIRCEP.113.000114 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 203WB UT WOS:000323323900033 PM 23884196 ER PT J AU Gutierrez, A Tsai, TT Stanislawski, MA Vidovich, M Bryson, CL Bhatt, DL Grunwald, GK Rumsfeld, J Rao, SV AF Gutierrez, Antonio Tsai, Thomas T. Stanislawski, Maggie A. Vidovich, Mladen Bryson, Christopher L. Bhatt, Deepak L. Grunwald, Gary K. Rumsfeld, John Rao, Sunil V. TI Adoption of Transradial Percutaneous Coronary Intervention and Outcomes According to Center Radial Volume in the Veterans Affairs Healthcare System Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE blood transfusion; hemorrhage; percutaneous coronary intervention; radial artery ID ACUTE MYOCARDIAL-INFARCTION; FEMORAL ACCESS; TASK-FORCE; ANGIOGRAPHY; ASSOCIATION; MORTALITY; IMPACT; TRIAL; GUIDELINES; SOCIETY AB Background-Studies examining the association between radial approach and post-percutaneous coronary intervention (PCI) bleeding and mortality have reached conflicting conclusions. There are no current data about the use and outcomes of transradial PCI (r-PCI) in the Veterans Affairs system. Methods and Results-Consecutive veterans (n=24143 patients) undergoing PCI in the Veterans Affairs between 2007 and 2010 were examined. On the basis of propensity to undergo r-PCI, 3 cohorts matched with veterans undergoing transfemoral access were constructed among sites performing >= 1 r-PCI, >= 50 r-PCI (high volume), and <50 r-PCI (low volume). Cox proportional hazard models were used to determine the association between PCI access site, blood transfusion, and mortality. The prevalence of r-PCI increased over time (2007=2.1%; 2010=8.8%). Overall, there was no difference in procedure success between matched groups (r-PCI 97.3% versus transfemoral PCI 96.6%; P=0.182), or in the risk of postprocedure transfusion or mortality. Among matched patients treated at high r-PCI volume sites, radial access was associated with a decreased risk of post-PCI blood transfusion (hazard ratio, 0.4; 95% confidence interval, 0.3-0.7; P<0.001), and no significant difference in the risk of mortality (hazard ratio, 0.7; 95% confidence interval, 0.4-1.3; P=0.279). Conclusions-Within the Veterans Affairs, the use of r-PCI increased over time. r-PCI may be associated with a significant decreased risk of post-PCI blood transfusion among higher volume r-PCI sites. These data demonstrate that potential benefits of r-PCI in terms of reduced post-PCI blood transfusions may be more pronounced at sites that routinely use radial access. C1 [Gutierrez, Antonio; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Tsai, Thomas T.; Stanislawski, Maggie A.; Grunwald, Gary K.; Rumsfeld, John] Univ Colorado Denver, VA Eastern Colorado Healthcare Syst, Aurora, CO USA. [Vidovich, Mladen] Univ Illinois, VA Med Ctr, Chicago, IL USA. [Bryson, Christopher L.] Seattle VA Med Ctr, Seattle, WA USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Rao, Sunil V.] Duke Clin Res Inst, Durham VA Med Ctr, Durham, NC USA. RP Gutierrez, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM Antonio.Gutierrez3@va.gov NR 28 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD AUG PY 2013 VL 6 IS 4 BP 336 EP 346 DI 10.1161/CIRCINTERVENTIONS.113.000110 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 203VX UT WOS:000323323300007 PM 23941860 ER PT J AU Goodrich, DE Kilbourne, AM Nord, KM Bauer, MS AF Goodrich, David E. Kilbourne, Amy M. Nord, Kristina M. Bauer, Mark S. TI Mental Health Collaborative Care and its Role in Primary Care Settings SO CURRENT PSYCHIATRY REPORTS LA English DT Article DE Mental health; Co-occurring conditions; Primary care; PCP; Integrated care; Collaborative care; Chronic care model; CCM; Accountable care organization; ACO; Patient-centered medical home; Screening; Diagnosis; Treatment; Access; Mental health services; Psychiatry; Bipolar disorder; Mood disorder; Substance abuse disorder; Anxiety disorder; Serious mental illness ID RANDOMIZED-CONTROLLED-TRIAL; MAJOR DEPRESSIVE DISORDER; BIPOLAR DISORDER; UNITED-STATES; MEDICATION ADHERENCE; PSYCHIATRIC-SERVICES; COST-EFFECTIVENESS; BRIEF INTERVENTION; FAMILY PHYSICIANS; COMPLEX PATIENTS AB Collaborative care models (CCMs) provide a pragmatic strategy to deliver integrated mental health and medical care for persons with mental health conditions served in primary care settings. CCMs are team-based intervention to enact system-level redesign by improving patient care through organizational leadership support, provider decision support, and clinical information systems, as well as engaging patients in their care through self-management support and linkages to community resources. The model is also a cost-efficient strategy for primary care practices to improve outcomes for a range of mental health conditions across populations and settings. CCMs can help achieve integrated care aims underhealth care reform yet organizational and financial issues may affect adoption into routine primary care. Notably, successful implementation of CCMs in routine care will require alignment of financial incentives to support systems redesign investments, reimbursements for mental health providers, and adaptation across different practice settings and infrastructure to offer all CCM components. C1 [Goodrich, David E.; Kilbourne, Amy M.; Nord, Kristina M.] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI 48109 USA. [Goodrich, David E.; Kilbourne, Amy M.; Nord, Kristina M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Kilbourne, AM (reprint author), VA Ann Arbor Ctr Clin Management Res, North Campus Res Complex,2800 Plymouth Rd,Bldg 16, Ann Arbor, MI 48109 USA. EM amykilbo@umich.edu OI Goodrich, David/0000-0003-3232-2189 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [HSRD IIR 10-340]; VA Health Services Research and Development Center for Organization, Leadership, and Management Research (COLMR); National Institute of Mental Health [RO1 MH 79994, R34 MH 74509]; University of Michigan Comprehensive Depression Center FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [HSRD IIR 10-340], the VA Health Services Research and Development Center for Organization, Leadership, and Management Research (COLMR), the National Institute of Mental Health [RO1 MH 79994 and R34 MH 74509], and the University of Michigan Comprehensive Depression Center (Director's Innovation Fund). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 98 TC 15 Z9 15 U1 2 U2 44 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 AUG PY 2013 VL 15 IS 8 AR 383 DI 10.1007/s11920-013-0383-2 PG 12 WC Psychiatry SC Psychiatry GA 202VN UT WOS:000323248300009 PM 23881714 ER PT J AU Peterfreund, RA Philip, JH AF Peterfreund, Robert A. Philip, James H. TI Critical parameters in drug delivery by intravenous infusion SO EXPERT OPINION ON DRUG DELIVERY LA English DT Review DE drug delivery by infusion; infusion pumps; intravenous infusion; medication safety ID BLOOD-STREAM INFECTIONS; INTENSIVE-CARE UNITS; SYRINGE PUMPS; ADMINISTRATION SETS; DROP SIZE; FLOW-RATE; IN-VITRO; POLYVINYL-CHLORIDE; DEAD-VOLUME; FLUID-FLOW AB Introduction: Intravenous infusion is commonly used to deliver medications and fluids to patients. The duration of an infusion is short (hours) in the operating room where intravenous agents are infused to anesthetize patients and to manage circulation. Critically ill patients often receive infusions for days. Infusion technology has become increasingly sophisticated and complex. The technical advances broaden the clinical application of intravenous infusion methodology and provide safety features. Areas covered: This article provides an historical overview of intravenous infusion and discusses components of infusion systems. A section describes configuration of components to meet clinical needs. The article describes physical properties of infusion systems, emphasizing how critical parameters of resistance to flow, infusion pump performance and interactions between fluid flows and the dead volume influence medication and fluid delivery. The authors emphasize the use of infusions in the intensive care and operating room environments, although the general principles apply to other clinical settings. Expert opinion: Intravenous infusion systems contribute significantly to clinical care, but in a deceptively simple way. Several critical parameters combine to influence the performance of an infusion system, with a number of pitfalls potentially confounding utility of the technology. Safe and effective clinical application of intravenous infusion technology depends on an appreciation of this complexity which impacts the performance of infusion systems. C1 [Peterfreund, Robert A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Philip, James H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Peterfreund, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM RPeterfreund@Partners.org NR 62 TC 8 Z9 8 U1 3 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5247 J9 EXPERT OPIN DRUG DEL JI Expert Opin. Drug Deliv. PD AUG PY 2013 VL 10 IS 8 BP 1095 EP 1108 DI 10.1517/17425247.2013.785519 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 198OL UT WOS:000322932100006 PM 23565777 ER PT J AU Borzutzky, A Camargo, CA AF Borzutzky, Arturo Camargo, Carlos A., Jr. TI Role of vitamin D in the pathogenesis and treatment of atopic dermatitis SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Review DE allergy; atopic dermatitis; cathelicidin; dendritic cells; epidermal barrier; filaggrin; latitude; Staphylococcus aureus; tolerance; vitamin D ID PLASMACYTOID DENDRITIC CELLS; SERUM 25-HYDROXYVITAMIN D; CD4(+) T-CELLS; RANDOMIZED CONTROLLED-TRIAL; HUMAN BETA-DEFENSINS; 1,25-DIHYDROXYVITAMIN D-3; D SUPPLEMENTATION; TH2 CELLS; IN-VITRO; EPIDERMAL DIFFERENTIATION AB Atopic dermatitis (AD) is a highly prevalent allergic skin disease that affects children worldwide. Epidemiological, clinical and basic immunological studies have suggested an association between vitamin D (VD) deficiency and the development of AD and other allergic diseases. Low levels of VD, a pleiotropic hormone that has widespread effects on the immune system and skin integrity, appear to be inversely correlated with AD severity, and VD deficiency at birth is associated with higher risk of developing AD. Recent randomized trials have reported inconsistent, but still promising, results on whether VD supplementation may improve AD severity. The apparent differences are likely due to small samples, different regimens and different patient populations. The mechanisms underlying this potential improvement in AD severity remain under investigation. C1 [Borzutzky, Arturo] Pontificia Univ Catolica Chile, Allergy Immunol & Rheumatol Unit, Div Pediat, Sch Med, Santiago, Chile. [Borzutzky, Arturo] Pontificia Univ Catolica Chile, Sch Med, Millennium Inst Immunol & Immunotherapy, Santiago, Chile. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Borzutzky, A (reprint author), Pontificia Univ Catolica Chile, Allergy Immunol & Rheumatol Unit, Div Pediat, Sch Med, Alameda 340, Santiago, Chile. EM arturobor@med.puc.cl OI Borzutzky, Arturo/0000-0002-7904-262X FU Fondecyt [1130615]; NIH [R01 AI093723, U01 AI087881] FX A Borzutzky is supported by Fondecyt Grant 1130615. CA Camargo is supported by NIH grants R01 AI093723 and U01 AI087881. 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 102 TC 5 Z9 6 U1 1 U2 12 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD AUG PY 2013 VL 9 IS 8 BP 751 EP 760 DI 10.1586/1744666X.2013.816493 PG 10 WC Immunology SC Immunology GA 205FP UT WOS:000323428600008 PM 23971753 ER PT J AU Vaduganathan, M Gheorghiade, M Butler, J AF Vaduganathan, Muthiah Gheorghiade, Mihai Butler, Javed TI Expanding the Scope of the "Polypill" to Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID REDUCED EJECTION FRACTION; READMISSION; THERAPY C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Butler, Javed] Emory Univ Hosp, Div Cardiol, Atlanta, GA 30322 USA. RP Vaduganathan, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM mvaduganathan@partners.org NR 9 TC 2 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2013 VL 19 IS 8 BP 540 EP 541 DI 10.1016/j.cardfail.2013.05.017 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201LF UT WOS:000323142400003 PM 23910582 ER PT J AU Manzano-Fernandez, S Flores-Blanco, PJ Perez-Calvo, JI Ruiz-Ruiz, FJ Carrasco-Sanchez, FJ Morales-Rull, JL Galisteo-Almeda, L Pascual-Figal, D Valdes, M Januzzi, JL AF Manzano-Fernandez, Sergio Flores-Blanco, Pedro J. Perez-Calvo, Juan I. Ruiz-Ruiz, Francisco J. Carrasco-Sanchez, Francisco J. Morales-Rull, Jose L. Galisteo-Almeda, Luis Pascual-Figal, Domingo Valdes, Mariano Januzzi, James L. TI Comparison of Risk Prediction With the CKD-EPI and MDRD Equations in Acute Decompensated Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Acute heart failure; prognosis; CKD-EPI; MDRD ID GLOMERULAR-FILTRATION-RATE; BETA-TRACE-PROTEIN; SERUM CYSTATIN-C; CHRONIC KIDNEY-DISEASE; RENAL-FUNCTION; CARDIOVASCULAR EVENTS; PROGNOSTIC VALUE; ELDERLY PERSONS; ESTIMATING GFR; CREATININE AB Background: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on. serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF). Methods and Results: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for FIEF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively). Conclusions: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification. C1 [Manzano-Fernandez, Sergio; Flores-Blanco, Pedro J.; Pascual-Figal, Domingo; Valdes, Mariano] Univ Murcia, Univ Hosp Virgen de la Arrixaca, Div Cardiol, Sch Med, Murcia 30120, Spain. [Perez-Calvo, Juan I.; Ruiz-Ruiz, Francisco J.] Univ Zaragoza, Fac Med, Hosp Clin Univ Lozano Blesa, Med Interna Serv, Zaragoza, Spain. [Perez-Calvo, Juan I.] Inst Invest Sanitaria Aragon, Zaragoza, Spain. [Carrasco-Sanchez, Francisco J.] Hosp Juan Ramon Jimenez, Med Interna Serv, Huelva, Spain. [Morales-Rull, Jose L.] Hosp Arnau Vilanova, Med Interna Serv, Lerida, Spain. [Galisteo-Almeda, Luis] Hosp Juan Ramon Jimenez, Serv Bioquim Clin & Lab, Huelva, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Manzano-Fernandez, S (reprint author), Univ Murcia, Univ Hosp Virgen de la Arrixaca, Div Cardiol, Sch Med, Carretera Madrid Cartagena S-N, Murcia 30120, Spain. EM sergiosmf13@hotmail.com RI Pascual Figal, Domingo /B-3794-2008; OI Pascual Figal, Domingo /0000-0002-4993-9540; Perez-Calvo, Juan Ignacio/0000-0003-2361-9941 NR 29 TC 14 Z9 15 U1 3 U2 9 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2013 VL 19 IS 8 BP 583 EP 591 DI 10.1016/j.cardfail.2013.05.011 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201LF UT WOS:000323142400010 PM 23910589 ER PT J AU Fourman, LT Meyer, BR AF Fourman, Lindsay T. Meyer, B. Robert TI Autoimmune Hepatitis in Association With Ramelteon SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE ramelteon; melatonin; hepatitis; autoimmunity ID ALCOHOLIC LIVER-DISEASE; MELATONIN RECEPTORS; HEPATOTOXICITY; CITALOPRAM; CELLS AB Ramelteon is a nonscheduled insomnia medication that lacks the abuse potential and residual effects common for other sedative-hypnotics. Distinct in its mechanism, the drug is a melatonin agonist with a high affinity for the membrane receptors MT1 and MT2. Although it therapeutically targets the suprachiasmatic nucleus of the hypothalamus, many organ systems have melatonin receptors and thus may be influenced by ramelteon. A growing body of research on melatonin indicates that it modulates the immune system. Indeed, immune cells have been shown to synthesize and to respond to this compound through receptors including MT1 and MT2. Melatonin's effects are generally immunostimulatory, and there is evidence to suggest that the chemical may potentiate autoimmunty. Here, we describe a case of autoimmune hepatitis that developed in a 50-year-old man after starting ramelteon for insomnia. The temporal association between ramelteon initiation and disease development, as well as the immunomodulatory properties of melatonergic compounds, suggest a role for ramelteon in the etiology of his illness. C1 [Fourman, Lindsay T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Meyer, B. Robert] New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Med, New York, NY USA. RP Fourman, LT (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM lindsayfourman@gmail.com NR 24 TC 3 Z9 3 U1 0 U2 1 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 AUG PY 2013 VL 47 IS 7 BP 651 EP 654 DI 10.1097/MCG.0b013e31829174f0 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 202OS UT WOS:000323228000014 PM 23632362 ER PT J AU Lerman, MA Burnham, JM Chang, PY Daniel, E Foster, CS Hennessy, S Jabs, DA Joffe, MM Kacmaz, RO Levy-Clarke, GA Mills, MD Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Kempen, JH AF Lerman, Melissa A. Burnham, Jon M. Chang, Peter Y. Daniel, Ebenezer Foster, C. Stephen Hennessy, Sean Jabs, Douglas A. Joffe, Marshall M. Kacmaz, R. Oktay Levy-Clarke, Grace A. Mills, Monte D. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Kempen, John H. TI Response of Pediatric Uveitis to Tumor Necrosis Factor-alpha Inhibitors SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE UVEITIS; TUMOR NECROSIS FACTOR ANTAGONIST; JUVENILE IDIOPATHIC ARTHRITIS ID JUVENILE IDIOPATHIC ARTHRITIS; CHRONIC NONINFECTIOUS UVEITIS; REFRACTORY CHILDHOOD UVEITIS; OCULAR INFLAMMATORY DISEASES; TERM-FOLLOW-UP; RHEUMATOID-ARTHRITIS; INFLIXIMAB THERAPY; RISK-FACTORS; CASE SERIES; CHILDREN AB Objective. To evaluate the outcome of tumor necrosis factor-alpha inhibition (anti-TNF) for pediatric uveitis. Methods. We retrospectively assessed children (age <= 18 yrs) with noninfectious uveitis receiving anti-TNF at 5 uveitis centers and 1 pediatric rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at >= 2 consecutive ophthalmological examinations L 28 days apart while taking no oral and <= 2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses. Results. Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% CI 62%-87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI 51%-76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype among JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75%-80% lower rate of achieving quiescence under anti-TNF, independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis reactivated within 12 months of achieving quiescence in 14% of those continuing anti-TNF (95% CI 6%-31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI 1%-43%). Conclusion. Treatment with anti-TNF was successful and sustained in a majority of children with noninfectious uveitis, and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNF. C1 Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA. Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Ctr Clin Epidemiol & Biostat,Dept Epidemiol & Bio, Philadelphia, PA 19104 USA. Univ Penn, Perelman Sch Med SOM, Philadelphia, PA 19104 USA. Ocular Immunol & Uveitis Fdn, Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Chang, Peter Y.] New York Eye & Ear Infirm, New York, NY 10003 USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21218 USA. [Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Irvine, CA 92715 USA. [Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Levy-Clarke, Grace A.] Johnson & Johnson Vis Care, Jacksonville, FL USA. Childrens Hosp Philadelphia, Div Ophthalmol, Philadelphia, PA 19104 USA. Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR USA. Oregon Hlth & Sci Univ, Div Rheumatol, Dept Internal Med, Portland, OR USA. Portland VA Med Ctr, Dept Ophthalmol, Portland, OR USA. RP Lerman, MA (reprint author), Childrens Hosp Philadelphia, Div Rheumatol, Abramson Res Ctr, Suite 1102,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM lermanm@email.chop.edu FU Rheumatology Research Foundation Scientist Development Award; Autoimmunity Centers of Excellence, National Institute of Allergy and Infectious Diseases; National Eye Institute (NEI), US National Institutes of Health (NIH) [R01 EY014943]; National Institute on Aging [AG025152, AG035751]; NEI [U10 EY08052]; NIH [U10 EY08052]; Johns Hopkins University Bloomberg School of Public Health [U10 EY08057]; University of Wisconsin [U10 EY08067]; US Department of Veterans Affairs; Abbott; LuxBio Genentech; Bristol Myers Squibb; Novartis; EyeGate; RPB Sybil B. Harrington Special Scholars Award; Research to Prevent Blindness; Paul and Evanina Mackall Foundation FX Supported by a Rheumatology Research Foundation Scientist Development Award (Dr. Lerman); Autoimmunity Centers of Excellence, National Institute of Allergy and Infectious Diseases (Dr. Burnham); R01 EY014943 National Eye Institute (NEI), US National Institutes of Health (NIH; Drs. Daniel, Rosenbaum, Suhler, Thorne, and Kempen); grants AG025152 and AG035751 from the National Institute on Aging (Dr. Hennessy); cooperative agreements from the NEI and the NIH to the Mount Sinai School of Medicine (U10 EY08052), the Johns Hopkins University Bloomberg School of Public Health, (U10 EY08057), and the University of Wisconsin (U10 EY08067; Dr. Jabs); intramural funding from the NEI (Dr. Levy-Clarke, and previously, Dr. Nussenblatt); The US Department of Veterans Affairs (Dr. Suhler); research grants from Abbott, LuxBio Genentech, Bristol Myers Squibb, Novartis, EyeGate, and the RPB Sybil B. Harrington Special Scholars Award (Dr. Thorne); and Research to Prevent Blindness, and the Paul and Evanina Mackall Foundation (Dr. Kempen). NR 50 TC 17 Z9 17 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 2013 VL 40 IS 8 BP 1394 EP 1403 DI 10.3899/jrheum.121180 PG 10 WC Rheumatology SC Rheumatology GA 202CY UT WOS:000323192300025 PM 23818712 ER PT J AU Busl, KM Nogueira, RG Yoo, AJ Hirsch, JA Schwamm, LH Rost, NS AF Busl, Katharina M. Nogueira, Raul G. Yoo, Albert J. Hirsch, Joshua A. Schwamm, Lee H. Rost, Natalia S. TI Prestroke Dementia is Associated With Poor Outcomes After Reperfusion Therapy Among Elderly Stroke Patients SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Acute stroke; dementia; outcome; reperfusion therapy; tissue plasminogen activator ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; 80 YEARS OLD; RT-PA; INTRACEREBRAL HEMORRHAGE; THROMBOLYTIC THERAPY; INTRAVENOUS THROMBOLYSIS; CONTROLLED-TRIAL; DOUBLE-BLIND; EXPERIENCE AB Background: In elderly acute stroke patients, reperfusion therapy is often withheld. We sought to determine whether prestroke dementia contributed to poor outcomes after reperfusion therapy in these patients. Methods: All consecutive patients >= 80 years of age who received intravenous (IV) or intra-arterial reperfusion therapy (IAT) were identified in our Get With the Guidelines Stroke (GWTG-S) database. Vascular risk factors, presence of dementia, and outcomes were abstracted from the medical record. Dementia was recorded when listed in the medical history or when under medical treatment. Primary outcome was in-hospital mortality. Secondary outcome was discharge destination, "favorable" (home or rehabilitation facility) versus "unfavorable" (skilled nursing facility, hospice, or death). Multivariate logistic regression models were used to assess outcomes. Results: Of 153 patients, 72% received IV tissue plasminogen activator (tPA), 35% IAT, and 7% both. The mean age was 85.8 +/- 4.6 years; 13.6% had prestroke dementia. The in-hospital mortality rate was 35%. The likelihood of death increased with National Institutes of Health Stroke Scale (NIHSS; odds ratio [OR] 1.14; 95% confidence interval [CI] 1.07-1.21), IAT (OR 3.43; 95% CI 1.70-6.92), and dementia (OR 3.61; 95% CI 1.39-9.37), and decreased with IV tPA (OR 0.34; 95% CI 0.17-0.71). Increasing NIHSS (OR 0.90; 95% CI 0.85-0.95), symptomatic intracranial hemorrhage (OR 0.08; 95% CI 0.01-0.67), IAT (OR 0.43; 95% CI 0.22-0.84), and dementia (OR 0.37; 95% CI 0.14-0.97) decreased the likelihood of favorable discharge. In multivariate analysis, only NIHSS (OR 1.13; 95% CI 1.06-1.22) and dementia (OR 5.64; 95% CI 1.88-16.89) independently predicted death and unfavorable discharge destination. Conclusions: Among the elderly, prestroke dementia is a powerful independent predictor of in-hospital mortality after acute reperfusion therapy for stroke. Future investigations of thrombolysis outcomes in the elderly are warranted. C1 [Busl, Katharina M.; Nogueira, Raul G.; Schwamm, Lee H.; Rost, Natalia S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Boston, MA USA. [Yoo, Albert J.; Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurointervent Div, Boston, MA USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM nrost@partners.org OI Schwamm, Lee/0000-0003-0592-9145 FU National Institute of Neurological Disorders and Stroke (NINDS) [K23NS064052]; Penumbra, Inc. FX Dr Rost is supported by the National Institute of Neurological Disorders and Stroke (NINDS) (K23NS064052). Dr Nogueira is a member of the Physician Advisory Board for Concentric Medical, ev3 Neurovascular, Coaxia, Rapid Medical, and Neurointervention, and the site PI for the TREVO-2 Trial. He does not receive any consulting fees. Dr Yoo receives research funding from Penumbra, Inc. Dr Schwamm serves as chair of the AHA GWTG National Steering Committee (unpaid), a member of the international steering committee of the DIAS-4 trial (Lundbeck), and a stroke systems consultant to the Massachusetts Department of Public Health. The other authors have nothing to disclose. NR 28 TC 12 Z9 13 U1 1 U2 6 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 AUG PY 2013 VL 22 IS 6 BP 718 EP 724 DI 10.1016/j.jstrokecerebrovasdis.2011.11.005 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 206DM UT WOS:000323497700004 PM 22182760 ER PT J AU Yoo, AJ Sheth, KN Kimberly, WT Chaudhry, ZA Elm, JJ Jacobson, S Davis, SM Donnan, GA Albers, GW Stern, BJ Gonzalez, RG AF Yoo, Albert J. Sheth, Kevin N. Kimberly, W. Taylor Chaudhry, Zeshan A. Elm, Jordan J. Jacobson, Sven Davis, Stephen M. Donnan, Geoffrey A. Albers, Gregory W. Stern, Barney J. Gonzalez, R. Gilberto TI Validating Imaging Biomarkers of Cerebral Edema in Patients With Severe Ischemic Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Acute ischemic stroke; biomarker subject codes 44 and 45; cerebral edema; magnetic resonance imaging; malignant stroke ID BRAIN EDEMA; ARTERY INFARCTION AB Background: There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints. Methods: Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume >82 cm(3) were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and days 3 to 5. We assessed interrater agreement, volume change between scans, and the association of volume change with early neurologic deterioration (National Institutes of Health Stroke Scale score worsening of >= 4 points), a 90-day modified Rankin scale (mRS) score of 0 to 4, and mortality. Results: Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm(3) and 234 cm(3), respectively. The mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2 +/- 8.3% (P < .0001), and the mean percent ventricle volume decrease was 45.6 +/- 16.9% (P < .001). Percent hemisphere growth predicted early neurologic deterioration (area under the curve [AUC] 0.92; P = .0005) and 90-day mRS 0 to 4 (AUC 0.80; P = .02). Conclusions: In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation. C1 [Yoo, Albert J.; Chaudhry, Zeshan A.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sheth, Kevin N.; Stern, Barney J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Elm, Jordan J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Jacobson, Sven] Remedy Pharmaceut, New York, NY USA. [Davis, Stephen M.] Royal Melbourne Hosp, Dept Med & Neurol, Parkville, Vic 3050, Australia. [Donnan, Geoffrey A.] Univ Melbourne, Florey Neurosci Inst, Parkville, Vic 3052, Australia. [Albers, Gregory W.] Stanford Univ, Med Ctr, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Albers, Gregory W.] Stanford Stroke Ctr, Stanford, CA USA. RP Sheth, KN (reprint author), 110 S Paca St,3rd Fl, Baltimore, MD 21201 USA. EM ksheth@som.umaryland.edu RI Davis, Stephen/L-5260-2013; OI Davis, Stephen/0000-0003-0962-2300; Donnan, Geoffrey/0000-0001-6324-3403 FU Penumbra, Inc; American Academy of Neurology Clinical Research Award; American Heart Association Clinical Research Award; Remedy Pharmaceuticals, Inc.; Clinical Investigator Training Program: Beth Israel Deaconess Medical Center; Harvard Medical School; Pfizer, Inc; Merck Co [NIH 1K23NS076597]; Sanofi-Aventis; Boehringer Ingelheim; National Institutes of Health and Lundbeck; National Institutes of Health FX Dr. Yoo has received support from Penumbra, Inc for core imaging laboratory activities. Dr. Sheth is supported by research funding from the American Academy of Neurology Clinical Research Award, American Heart Association Clinical Research Award, and Remedy Pharmaceuticals, Inc. Dr. Kimberly is supported by an American Academy of Neurology Clinical Research Award, Clinical Investigator Training Program: Beth Israel Deaconess Medical Center, Harvard Medical School, in collaboration with Pfizer, Inc and Merck & Co (NIH 1K23NS076597). Mr. Jacobson is the CEO of Remedy Pharmaceticals. Dr. Davis serves on the advisory boards of PAION, Servier, and Novo Nordisk, and has received honoraria from Novo Nordisk, Sanofi-Aventis, Pfizer, and Boehringer Ingelheim. Dr. Donnan serves on the advisory boards of Boehringer Ingelheim, PAION, Servier, and Sanofi-Aventis; has received honoraria or consulting payments from and has had costs of participating in scientific meetings reimbursed by Boehringer Ingelheim, Sanofi-Aventis, and Servier; and has received grant funding from Sanofi-Aventis and grants and consultancy payments from Boehringer Ingelheim. Dr. Albers has received grant funding from the National Institutes of Health and Lundbeck; is a consultant for Lundbeck; and holds equity in iSchema View. Dr. Stern is supported by the National Institutes of Health. Drs. Chaudhry, Elm, and Gonzalez have no conflicts of interest to declare. NR 14 TC 9 Z9 9 U1 1 U2 3 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 AUG PY 2013 VL 22 IS 6 BP 742 EP 749 DI 10.1016/j.jstrokecerebrovasdis.2012.01.002 PG 8 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 206DM UT WOS:000323497700008 PM 22325573 ER PT J AU Fang, PA Margolis, HC Conway, JF Simmer, JP Beniash, E AF Fang, Ping-An Margolis, Henry C. Conway, James F. Simmer, James P. Beniash, Elia TI CryoTEM study of effects of phosphorylation on the hierarchical assembly of porcine amelogenin and its regulation of mineralization in vitro SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Biomineralization; Cryo Transmission Electron Microscopy; Single particle reconstruction; Self-assembly; Enamel; Amelogenin ID CALCIUM-PHOSPHATE FORMATION; ENAMEL MATRIX; TOOTH ENAMEL; IMPERFECTA PHENOTYPE; MOUSE AMELOGENINS; MICE DISPLAY; PROTEIN; BIOMINERALIZATION; TEMPERATURE; IDENTIFICATION AB Amelogenin, the major extracellular enamel matrix protein, plays a critical role in regulating the growth and organization of enamel. Assembly and mineralization of full-length native (P173) and recombinant (rP172) porcine amelogenins were studied by cryogenic Transmission Electron Microscopy (cryoTEM). The cryoTEM revealed that both native and recombinant porcine amelogenins undergo step-wise self-assembly. Although the overall structural organization of P173 and rP172 oligomers was similar and resembled oligomers of murine recombinant amelogenin rM179, there were subtle differences suggesting that a single phosphorylated serine present in P173 might affect amelogenin self-assembly. Our mineralization studies demonstrated that both P173 and rP172 oligomers stabilize initial mineral clusters. Importantly, however, rP172 regulated the organization of initial mineral clusters into linear chains and guided the formation of parallel arrays of elongated mineral particles, which are the hallmark of enamel structural organization. These results are similar to those obtained previously using full-length recombinant murine amelogenin (Fang et al., 2011a). In contrast to that seen with rP172, phosphorylated P173 strongly inhibits mineralization for extended periods of time. We propose that these differences might be due to the differences in the structural organization and charge distribution between P173 and rP172. Overall our studies indicate that self-assembly of amelogenin and the mechanisms of its control over mineralization might be universal across different mammalian species. Our data also provide new insight into the effect of phosphorylation on amelogenin self-assembly and its regulation of mineralization. (C) 2013 Elsevier Inc. All rights reserved. C1 [Fang, Ping-An; Beniash, Elia] Univ Pittsburgh, Dept Oral Biol, Ctr Craniofacial Regenerat, McGowan Inst Regenerat Med, Pittsburgh, PA 15261 USA. [Margolis, Henry C.] Forsyth Inst, Ctr Biomineralizat, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Conway, James F.] Univ Pittsburgh, Dept Biol Struct, Pittsburgh, PA 15261 USA. [Simmer, James P.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Beniash, E (reprint author), Univ Pittsburgh, Dept Oral Biol, Ctr Craniofacial Regenerat, McGowan Inst Regenerat Med, Pittsburgh, PA 15261 USA. EM ebeniash@pitt.edu FU NIH [R56DE016376, R01DE023091, R56DE016703] FX These studies were supported by NIH grants R56DE016376 (to H.C.M.), R01DE023091 (to H.C.M.), and R56DE016703 (to E.B.). NR 47 TC 9 Z9 9 U1 2 U2 29 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 EI 1095-8657 J9 J STRUCT BIOL JI J. Struct. Biol. PD AUG PY 2013 VL 183 IS 2 BP 250 EP 257 DI 10.1016/j.jsb.2013.05.011 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 204XU UT WOS:000323405400016 PM 23707542 ER PT J AU Cohen, ME Ko, CY Bilimoria, KY Zhou, L Huffman, K Wang, X Liu, YM Kraemer, K Meng, XJ Merkow, R Chow, W Matel, B Richards, K Hart, AJ Dimick, JB Hall, BL AF Cohen, Mark E. Ko, Clifford Y. Bilimoria, Karl Y. Zhou, Lynn Huffman, Kristopher Wang, Xue Liu, Yaoming Kraemer, Kari Meng, Xiangju Merkow, Ryan Chow, Warren Matel, Brian Richards, Karen Hart, Amy J. Dimick, Justin B. Hall, Bruce L. TI Optimizing ACS NSQIP Modeling for Evaluation of Surgical Quality and Risk: Patient Risk Adjustment, Procedure Mix Adjustment, Shrinkage Adjustment, and Surgical Focus SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SUPPORT VECTOR MACHINE; IMPROVEMENT PROGRAM; HOSPITAL OUTCOMES; PREDICTION MODELS; MORTALITY-RATE; REPORT CARDS; ROC CURVE; SURGERY; PERFORMANCE; REGRESSION AB The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) collects detailed clinical data from participating hospitals using standardized data definitions, analyzes these data, and provides participating hospitals with reports that permit risk-adjusted comparisons with a surgical quality standard. Since its inception, the ACS NSQIP has worked to refine surgical outcomes measurements and enhance statistical methods to improve the reliability and validity of this hospital profiling. From an original focus on controlling for between-hospital differences in patient risk factors with logistic regression, ACS NSQIP has added a variable to better adjust for the complexity and risk profile of surgical procedures (procedure mix adjustment) and stabilized estimates derived from small samples by using a hierarchical model with shrinkage adjustment. New models have been developed focusing on specific surgical procedures (eg, "Procedure Targeted" models), which provide opportunities to incorporate indication and other procedure-specific variables and outcomes to improve risk adjustment. In addition, comparative benchmark reports given to participating hospitals have been expanded considerably to allow more detailed evaluations of performance. Finally, procedures have been developed to estimate surgical risk for individual patients. This article describes the development of, and justification for, these new statistical methods and reporting strategies in ACS NSQIP. (C) 2013 by the American College of Surgeons C1 [Cohen, Mark E.; Ko, Clifford Y.; Bilimoria, Karl Y.; Zhou, Lynn; Huffman, Kristopher; Wang, Xue; Liu, Yaoming; Kraemer, Kari; Meng, Xiangju; Merkow, Ryan; Chow, Warren; Matel, Brian; Richards, Karen; Hart, Amy J.; Hall, Bruce L.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Bilimoria, Karl Y.] Northwestern Univ, Surg Outcomes & Qual Improvement Ctr, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dimick, Justin B.] Univ Michigan, Dept Surg, Michigan Surg Collaborat Outcomes Res & Evaluat, Ann Arbor, MI 48109 USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, BJC Healthcare, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, St Louis, MO USA. RP Cohen, ME (reprint author), Amer Coll Surg, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM markcohen@facs.org NR 47 TC 141 Z9 142 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2013 VL 217 IS 2 BP 336 EP + DI 10.1016/j.jamcollsurg.2013.02.027 PG 12 WC Surgery SC Surgery GA 201TX UT WOS:000323167000022 PM 23628227 ER PT J AU Hanlon, JT Schmader, KE Semla, TP AF Hanlon, Joseph T. Schmader, Kenneth E. Semla, Todd P. TI Update of Studies on Drug-Related Problems in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aged; drug utilization; adverse drug event ID HOSPITALIZATIONS C1 [Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Geriatr Pharmaceut Outcomes & Geroinformat Res &, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. [Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Semla, Todd P.] Pharm Benefits Management, Dept Vet Affairs, Hines, IL USA. [Semla, Todd P.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufman Med Bldg,Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu FU Agency for Healthcare Research and Quality [R01 HS018721, K12 HS019461]; National Institute of Aging [P30AG024827, T32 AG021885, K07AG033174, R01A G027017, R01 AG037451] FX The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Dr. Semla serves on the Omnicare Pharmacy and Therapeutics Committee (long-term care). He is an author and editor for LexiComp, Inc; his spouse is an employee of Abbott Labs. Dr. Hanlon is supported by Agency for Healthcare Research and Quality Grants R01 HS018721, and K12 HS019461 and National Institute of Aging Grants P30AG024827, T32 AG021885, K07AG033174, R01A G027017, and R01 AG037451. NR 13 TC 9 Z9 10 U1 0 U2 7 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 AUG PY 2013 VL 61 IS 8 BP 1365 EP 1368 DI 10.1111/jgs.12354 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 198ZY UT WOS:000322964500016 PM 23731022 ER PT J AU Hicks, JW Parkes, J Sadovski, O Tong, JC Houle, S Vasdev, N Wilson, AA AF Hicks, Justin W. Parkes, Jun Sadovski, Oleg Tong, Junchao Houle, Sylvain Vasdev, Neil Wilson, Alan A. TI Synthesis and preclinical evaluation of [C-11-carbonyl]PF-04457845 for neuroimaging of fatty acid amide hydrolase SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE FAAH; Positron emission tomography; Rodent models; Carbon-11; Radiotracer AB Introduction: Fatty acid amide hydrolase (FAAH) has a significant role in regulating endocannabinoid signaling in the central nervous system. As such, FAAH inhibitors are being actively sought for pain, addiction, and other indications. This has led to the recent pursuit of positron emission tomography (PET) radiotracers targeting FAAH. We report herein the preparation and preclinical evaluation of [C-11-carbonyl]PF-04457845, an isotopologue of the potent irreversible FAAH inhibitor. Methods: PF-04457845 was radiolabeled at the carbonyl position via automated [C-11]CO2-fixation. Ex vivo brain biodistribution of [C-11-carbonyl]PF-04457845 was carried out in conscious rats. Specificity was determined by pre-administration of PF-04457845 or URB597 prior to [C-11-carbonyl]PF-04457845. In a separate experiment, rats injected with the title radiotracer had whole brains excised, homogenized and extracted to examine irreversible binding to brain parenchyma. Results: The title compound was prepared in 5 +/- 1% (n = 4) isolated radiochemical yield based on starting [C-11]CO2 (decay uncorrected) within 25 min from end-of-bombardment in >98% radiochemical purity and a specific activity of 73.5 +/- 8.2 GBq/mu mol at end-of-synthesis. Uptake of [C-11-carbonyl]PF-04457845 into the rat brain was high (range of 1.2-4.4 SUV), heterogeneous, and in accordance with reported FAAH distribution. Saturable binding was demonstrated by a dose-dependent reduction in brain radioactivity uptake following pre-treatment with PF-04457845. Pre-treatment with the prototypical FAAH inhibitor, URB597, reduced the brain radiotracer uptake in all regions by 71-81%, demonstrating specificity for FAAH. The binding of [C-11-carbonyl]PF-04457845 to FAAH at 40 min post injection was irreversible as 98% of the radioactivity in the brain could not be extracted. Conclusions: [C-11-carbonyl]PF-04457845 was rapidly synthesized via an automated radiosynthesis. Ex vivo biodistribution studies in conscious rodents demonstrate that [C-11 PF-04457845 is a promising candidate radiotracer for imaging FAAH in the brain with PET. These results coupled with the known pharmacology and toxicology of PF-04457845 should facilitate clinical translation of this radiotracer. (C) 2013 Elsevier Inc. All rights reserved. C1 [Hicks, Justin W.; Parkes, Jun; Sadovski, Oleg; Tong, Junchao; Houle, Sylvain; Wilson, Alan A.] Ctr Addict & Mental Hlth, Res Imaging Ctr, Toronto, ON M5T 1R8, Canada. [Hicks, Justin W.; Wilson, Alan A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada. [Houle, Sylvain; Wilson, Alan A.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. [Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Wilson, AA (reprint author), CAMH, Res Imaging Ctr, Toronto, ON M5T 1R8, Canada. EM alan.wilson@camhpet.ca RI Wilson, Alan/A-1788-2011 FU NIH [1R21MH094424-01]; Ontario Ministry of Research and Development Early Researcher award; University of Toronto Institute of Medical Science Open Fellowship award FX This work was supported by NIH Grant # 1R21MH094424-01 to AAW, an Ontario Ministry of Research and Development Early Researcher award to NV, and a University of Toronto Institute of Medical Science Open Fellowship award to JWH. We would like to thank Armando Garcia, Winston Stableford, MM Wong, Virginia S. Wilson, Patrick McCormick, and Alvina Ng for their assistance with the radiochemistry and animal dissection experiments. NR 45 TC 14 Z9 14 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 2013 VL 40 IS 6 BP 740 EP 746 DI 10.1016/j.nucmedbio.2013.04.008 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 200RS UT WOS:000323087200004 PM 23731552 ER PT J AU Dearling, JLJ Barnes, JW Panigrahy, D Zimmerman, RE Fahey, F Treves, ST Morrison, MS Kieran, MW Packard, AB AF Dearling, Jason L. J. Barnes, Jessica W. Panigrahy, Dipak Zimmerman, Robert E. Fahey, Frederic Treves, S. Ted Morrison, Matthew S. Kieran, Mark W. Packard, Alan B. TI Specific uptake of Tc-99m-NC100692, an alpha(v)beta(3)-targeted imaging probe, in subcutaneous and orthotopic tumors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Angiogenesis; NC100692; MicroSPECT; alpha(v)beta(3); Brain tumor; RGD peptides; Cilengitide AB Introduction: The alpha(v)beta(3) integrin, which is expressed by angiogenic epithelium and some tumor cells, is an attractive target for the development of both imaging agents and therapeutics. While optimal implementation of alpha(v)beta(3)-targeted therapeutics will require a priori identification of the presence of the target, the clinical evaluation of these compounds has typically not included parallel studies with alpha(v)beta(3)-targeted diagnostics. This is at least partly due to the relatively limited availability of PET radiopharmaceuticals in comparison to those labeled with Tc-99m. In an effort to begin to address this limitation, we evaluated the tumor uptake of Tc-99m-NC100692, a cyclic RGD peptide that binds to alpha(v beta 3) with similar to 1-nM affinity, in an alpha(v)beta(3)-positive tumor model as well as its in vivo specificity. Methods: MicroSPECT imaging was used to assess the ability of cilengitide, a therapeutic with high affinity for alpha(v)beta(3), to block and displace Tc-99m-NC100692 in an orthotopic U87 glioma tumor. The specificity of Tc-99m-NC100692 was quantitatively evaluated in mice bearing subcutaneous U87MG tumors, by comparison of the biodistribution of Tc-99m-NC100692 with that of the non-specific structural analogue Tc-99m-AH-111744 and by blocking uptake of Tc-99m-NC100692 with excess unlabeled NC100692. Results: MicroSPECT imaging studies demonstrated that uptake of Tc-99m-NC100692 in the intracranial tumor model was both blocked and displaced by the alpha(v)beta(3)-targeted therapeutic cilengitide. Biodistribution studies provided quantitative confirmation of these imaging results. Tumor uptake of Tc-99m-NC100692 at 1 h post-injection was 2.8 +/- 0.7% ID/g compared to 0.38 +/- 0.1% ID/g for Tc-99m-AH-111744 (p < 0.001). Blocking Tc-99m-NC100692 uptake by pre-injecting the mice with excess unlabeled NC100692 reduced tumor uptake by approximately five-fold, to 0.68 +/- 0.3% ID/g (p = 0.01). Conclusion: These results confirm that Tc-99m-NC100692 does, in fact, target the alpha(v)beta(3) integrin and may, therefore, be useful in identifying patients prior to anti-alpha(v)beta(3) therapy as well as monitoring the response of these patients to therapy. (C) 2013 Elsevier Inc. All rights reserved. C1 [Dearling, Jason L. J.; Fahey, Frederic; Treves, S. Ted; Packard, Alan B.] Boston Childrens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Dearling, Jason L. J.; Barnes, Jessica W.; Panigrahy, Dipak; Zimmerman, Robert E.; Fahey, Frederic; Treves, S. Ted; Kieran, Mark W.; Packard, Alan B.] Harvard Univ, Sch Med, Boston, MA USA. [Barnes, Jessica W.; Panigrahy, Dipak; Kieran, Mark W.] Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Barnes, Jessica W.; Panigrahy, Dipak; Kieran, Mark W.] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA USA. [Barnes, Jessica W.; Panigrahy, Dipak; Kieran, Mark W.] Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA. [Barnes, Jessica W.; Panigrahy, Dipak; Kieran, Mark W.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Zimmerman, Robert E.] Grove Ctr, GE Healthcare, Amersham HP7 9LL, England. RP Dearling, JLJ (reprint author), Boston Childrens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. EM jason.dearling@childrens.harvard.edu FU Childhood Brain Tumor Foundation; Kyle Johnson Brain Tumor Fund; CJ Buckley Brain Tumor Research Fund; Stop&Shop Pediatric Brain Tumor Research Fund; Ralph and Andrea Faber Fund for Radiological Research; NIH [S10-RR17224] FX We thank Patricia Dunning, Erin Snay, Deviney Chaponis, Amanda Baker and Emily Greene for technical assistance. The assistance of Sharon Peled, PhD, in the acquisition of the MRI studies is gratefully acknowledged. Alice Carmel, BS, assisted with the mouse microSPECT studies. Kristin Johnson assisted with image preparation. NC100692 (maraciclatide) was provided by GE Healthcare (Amersham, UK). EMD121974 (cilengitide) was provided by Merck KGaA (Darmstadt, Germany). This work was supported by the Childhood Brain Tumor Foundation, the Kyle Johnson Brain Tumor Fund, the CJ Buckley Brain Tumor Research Fund, the Stop&Shop Pediatric Brain Tumor Research Fund and the Ralph and Andrea Faber Fund for Radiological Research. The microSPECT camera was purchased with NIH Grant S10-RR17224. NR 21 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 2013 VL 40 IS 6 BP 788 EP 794 DI 10.1016/j.nucmedbio.2013.04.006 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 200RS UT WOS:000323087200009 PM 23701702 ER PT J AU Hatoum, IJ Kaplan, LM AF Hatoum, Ida J. Kaplan, Lee M. TI Advantages of Percent Weight Loss as a Method of Reporting Weight Loss After Roux-en-Y Gastric Bypass SO OBESITY LA English DT Article ID BODY-MASS INDEX; BARIATRIC SURGERY; MORBID-OBESITY; BLOOD-PRESSURE; RISK-FACTORS; PREDICTOR; OVERWEIGHT; RATS AB Objective: Although Roux-en-Y gastric bypass (RYGB) is an effective treatment for severe obesity, weight loss (WL) after this operation is highly variable. Accurate predictors of outcome would thus be useful in identifying those patients who would most benefit from this invasive therapy. WL has been characterized using several different metrics, including the number of BMI units lost (Delta BMI), percent baseline WL (%WL), and percent excess body WL (%EBWL). To identify clinically relevant predictors most sensitively, it is necessary to avoid confounding by other factors, including preoperative BMI (pBMI), the strongest known predictor of RYGB-induced WL. Design and Methods: To determine the WL measure least associated with pBMI, outcomes of 846 patients undergoing RYGB were analyzed. Results: Patients in this cohort had an average pBMI of 50.0 kg/m(2) at baseline. At weight nadir, they lost an average 19.4 kg/m(2), 38.7% WL, and 81.2% EBWL. pBMI was strongly and positively associated with DBMI at both 1 year (r = 0.56, P = 4.7 x 10(-51)) and nadir (r = 0.58, P = 2.8 x 10(-77)) and strongly but negatively associated with %EBWL at 1 year (r = -0.52, P = 3.8 x 10(-44)) and nadir (r = -0.45, P = 7.2 x 10(-43)). In contrast, pBMI was not significantly associated with %WL at 1 year (r = 0.04, P = 0.33) and only weakly associated at nadir (r = 0.13, P = 0.0002). Conclusions: Of the metrics examined, %WL is the parameter describing WL after RYGB least influenced by pBMI. It thus improves comparison of WL outcomes across studies of patients undergoing surgery and facilitates the most sensitive identification of novel predictors of surgery-induced WL. We therefore is recommend that %WL be adopted more broadly in reporting weight loss after RYGB. C1 [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hatoum, Ida J.; Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. EM LMKaplan@partners.org FU NIH [DK093257, DK088661, DK090956] FX This work was supported by NIH grants DK093257 (IJH), DK088661 (LMK), and DK090956 (LMK). Additional Supporting Information may be found in the online version of this article. NR 41 TC 18 Z9 18 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD AUG PY 2013 VL 21 IS 8 BP 1519 EP 1525 DI 10.1002/oby.20186 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 206LE UT WOS:000323521500004 PM 23670991 ER PT J AU Murabito, JM Massaro, JM Clifford, B Hoffmann, U Fox, CS AF Murabito, Joanne M. Massaro, Joseph M. Clifford, Brian Hoffmann, Udo Fox, Caroline S. TI Depressive Symptoms Are Associated with Visceral Adiposity in a Community-Based Sample of Middle-Aged Women and Men SO OBESITY LA English DT Article ID CORONARY HEART-DISEASE; MAJOR DEPRESSION; ABDOMINAL OBESITY; TISSUE VOLUMES; OLDER PERSONS; FAT; MARKERS; HEALTH; OVERWEIGHT; DISORDERS AB Objective: To examine the relation between measures of adiposity and depressive symptoms in a large well characterized community-based sample, we examined the relations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) to depressive symptoms in 1,581 women (mean age 52.2 years) and 1,718 men (mean age 49.8 years) in the Framingham Heart Study. Design and Methods: Depressive symptoms were measured using the Center for Epidemiologic Studies Depression (CES-D) scale. Regression models were created to examine the association between each fat depot (exposure) and depressive symptoms (outcome). Sex-specific models were adjusted for age, body mass index, smoking, alcohol consumption, diabetes, hypertension, total and HDL cholesterol, lipid lowering treatment, CVD, menopause, C-reactive protein, and physical activity. Results: Mean CES-D scores were 6.8 and 5.6 in women and men. High levels of depressive symptoms were present in 22.5% of women and 12.3% of men. In women, one standard deviation increase in VAT was associated with a 1.3 point higher CES-D score after adjusting for age and BMI (P < 0.01) and remained significant in the fully adjusted model (P = 0.03). The odds ratio of depressive symptoms per 1 standard deviation increase in VAT in women was 1.33 (P = 0.015); results were attenuated in fully adjusted models (OR 1.29, P = 0.055). In men, the association between VAT and CES-D score and depressive symptoms was not significant. SAT was not associated with CES-D score or depressive symptoms. Conclusions: This study supports an association between VAT and depressive symptoms in women. Further work is needed to uncover the complex biologic mechanisms mediating the association. C1 [Murabito, Joanne M.; Clifford, Brian] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Murabito, Joanne M.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Cardiac MR PET CT, Boston, MA 02114 USA. [Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Murabito, JM (reprint author), Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. EM murabito@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU National Heart Blood and Lung Institute [N01-HC-25195] FX The Framingham Heart Study is funded by National Heart Blood and Lung Institute (contract N01-HC-25195). NR 33 TC 9 Z9 9 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 J9 OBESITY JI Obesity PD AUG PY 2013 VL 21 IS 8 BP 1713 EP 1719 DI 10.1002/oby.20130 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 206LE UT WOS:000323521500031 PM 23666906 ER PT J AU Plagge, JM Lu, MW Lovejoy, TI Karl, AI Dobscha, SK AF Plagge, Jane M. Lu, Mary W. Lovejoy, Travis I. Karl, Andrea I. Dobscha, Steven K. TI Treatment of Comorbid Pain and PTSD in Returning Veterans: A Collaborative Approach Utilizing Behavioral Activation SO PAIN MEDICINE LA English DT Article DE Pain; Posttraumatic Stress Disorder; Veterans; Behavioral Activation; Collaborative Care ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH TREATMENT; MUSCULOSKELETAL PAIN; PRIMARY-CARE; PSYCHOMETRIC PROPERTIES; DEPRESSION; AFGHANISTAN; SCALE; IRAQ; INTERVENTION AB Objective. We explore preliminary clinical effectiveness and feasibility of an intervention utilizing collaborative care components and behavioral activation (BA) to treat comorbid chronic pain and posttraumatic stress disorder (PTSD). Design. Descriptive, including pre- and posttreatment assessment results. Setting. Portland Veterans Affairs Medical Center. Participants. Fifty-eight Iraq and Afghanistan veterans with chronic pain and PTSD symptoms. Interventions. Veterans participated in a biopsychosocial evaluation and up to eight BA sessions using a collaborative approach involving primary care, mental health, and other clinicians. A physiatrist assisted the psychologist in providing recommendations to primary care providers. Outcome Measures. Participants were administered pre-and posttreatment measures of PTSD, pain severity, pain interference, mental health, quality of life, satisfaction, and global ratings of change with the purpose of assessing progress and improving quality. Results. Of the 58 participants, 30 completed treatment. Common recommendations included physical therapy and exercise programs, pain medication or pain medication adjustments, and additional diagnostic workups, such as imaging. Participants who completed the program showed significant improvements on measures of PTSD, pain severity, and pain interference. Improvements were also evident on measures of mental health and quality of life. Overall, participants were satisfied with the program, and on average reported feeling "somewhat better." Conclusions. These findings suggest that a collaborative approach that includes BA is feasible and a potentially effective treatment for comorbid chronic pain and PTSD. C1 [Plagge, Jane M.; Lu, Mary W.; Lovejoy, Travis I.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Karl, Andrea I.] Portland VA Med Ctr, Dept Rehabil Med, Portland, OR 97239 USA. [Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR 97239 USA. [Plagge, Jane M.; Lu, Mary W.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Mental Hlth & Neurosci Div, 3710 SW US Vet Hosp Rd,POB 1034,P3MHADM, Portland, OR 97239 USA. EM steven.dobscha@va.gov FU Pacific Northwest Mental Illness Research and Education and Clinical Center (MIRECC); VA Mental Health Services FX No author reports having any financial or other potential conflict of interest with this study. 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. This work was supported by the Pacific Northwest Mental Illness Research and Education and Clinical Center (MIRECC) and VA Mental Health Services. The authors acknowledge Alex Linke, BS, for assistance with utilization data extraction, and Amy Wagner, PhD, for assistance in implementing behavioral activation and for reviewing the manuscript. NR 44 TC 5 Z9 5 U1 5 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD AUG PY 2013 VL 14 IS 8 BP 1164 EP 1172 DI 10.1111/pme.12155 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 202FP UT WOS:000323199400008 PM 23746043 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Medical Comorbidity is Associated with Persistent Index Hip Pain after Total Hip Arthroplasty SO PAIN MEDICINE LA English DT Article DE Pain; Function; Functional Limitation; Total Hip Replacement; Primary; Arthroplasty; Joint Replacement; Outcomes; Patient-Reported Outcomes ID QUALITY-OF-LIFE; CHRONIC KIDNEY-DISEASE; KNEE ARTHROPLASTY; RHEUMATOID-ARTHRITIS; FUNCTIONAL STATUS; REVISION HIP; OUTCOMES; REPLACEMENT; HEALTH; RISK AB Objective. To characterize whether medical comorbidity predicts persistent moderate-severe pain after total hip arthroplasty (THA). Methods. We analyzed the prospectively collected data from the Mayo Clinic Total Joint Registry for patients who underwent primary or revision THA between 1993 and 2005. Using multivariable-adjusted logistic regression analyses, we examined whether certain medical comorbidities were associated with persistent moderate-severe hip pain 2 or 5 years after primary or revision THA. Odds ratios (ORs), along with 95% confidence intervals (CIs) and P value, are presented. Results. The primary THA cohort consisted of 5,707 THAs and 3,289 THAs at 2 and 5 years, and revision THA, 2,687 and 1,627 THAs, respectively. In multivariable-adjusted logistic regression models, in the primary THA cohort, renal disease was associated with lower odds of moderate-severe hip pain (OR 0.6; 95% CI 0.3, 1.0) at 2 years. None of the comorbidities were significantly associated at 5 years. In the revision THA cohort, heart disease was significantly associated with higher risk (OR 1.7; 95% CI 1.1, 2.6) at 2 years and connective tissue disease with lower risk (OR 0.5; 95% CI 0.3, 0.9) of moderate-severe hip pain at 5-year follow-up. Conclusion. This study identified new correlates of moderate-severe hip pain after primary or revision THA, a much-feared outcome of hip arthroplasty. Patients with these comorbidities should be informed regarding the risk of moderate-severe index hip pain, so that they can have a fully informed consent and realistic expectations. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. 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 Mayo Clinic Orthopedic Surgery research funds; National Institutes of Health (NIH) Clinical Translational Science Award [1 KL2 RR024151-01]; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Aging and National Cancer Institute FX This material is the result of work supported with research grants from the Mayo Clinic Orthopedic Surgery research funds, National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Aging and National Cancer Institute. NR 35 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD AUG PY 2013 VL 14 IS 8 BP 1222 EP 1229 DI 10.1111/pme.12153 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 202FP UT WOS:000323199400014 PM 23742141 ER PT J AU Huang, LW Choi, SY Chacon-Heszele, M Ryu, YK McKenna, S Zuo, XF Kuruvilla, R Lipschutz, J AF Huang, Liwei Choi, Soo Young Chacon-Heszele, Maria Ryu, Yun Kyoung McKenna, Sarah Zuo, Xiaofeng Kuruvilla, Rejji Lipschutz, Josh TI The Role of Wnt5a in Pronephric and Metanephric Kidney Development SO PEDIATRIC NEPHROLOGY LA English DT Meeting Abstract C1 [Huang, Liwei; Choi, Soo Young; Chacon-Heszele, Maria; McKenna, Sarah; Zuo, Xiaofeng; Lipschutz, Josh] Univ Penn, Philadelphia, PA 19104 USA. [Ryu, Yun Kyoung; Kuruvilla, Rejji] Johns Hopkins Univ, Baltimore, MD USA. [Lipschutz, Josh] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD AUG PY 2013 VL 28 IS 8 BP 1348 EP 1348 PG 1 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 177PJ UT WOS:000321387201012 ER PT J AU Siever, L AF Siever, Larry TI Paranoid case vignette SO PERSONALITY AND MENTAL HEALTH LA English DT Editorial Material C1 [Siever, Larry] Icahn Sch Med Mt Sinai, New York, NY USA. [Siever, Larry] James J Peters VA Med Ctr, Psychiat Program, Bronx, NY USA. RP Siever, L (reprint author), James J Peters VA Med Ctr, Psychiat Program, Bronx, NY USA. EM larry.siever@mssm.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8621 J9 PERSONAL MENT HEALTH JI Personal. Ment. Health PD AUG PY 2013 VL 7 IS 3 BP 262 EP 263 DI 10.1002/pmh.1243 PG 2 WC Psychiatry; Psychology, Social SC Psychiatry; Psychology GA 201OS UT WOS:000323151900010 PM 24343970 ER PT J AU Kosten, TA Shen, XY O'Malley, PW Kinsey, BM Lykissa, ED Orson, FM Kosten, TR AF Kosten, Therese A. Shen, Xiaoyun Y. O'Malley, Patrick W. Kinsey, Berma M. Lykissa, Ernest D. Orson, Frank M. Kosten, Thomas R. TI A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Antinociception; Conditioned place preference; Heroin metabolites; Immunotherapy; Opioid dependence ID SERUM-ALBUMIN; HEROIN; METHADONE; PHARMACOTHERAPY; METABOLITES; ANTIBODIES; DEPENDENCE; ADDICTION; EFFICACY; COCAINE AB Vaccines for opioid dependence may provide a treatment that would reduce or slow the distribution of the drug to brain, thus reducing the drug's reinforcing effects. We tested whether a conjugate vaccine against morphine (keyhole limpet hemocyanin-6-succinylmorphine; KLH-6-SM) administered to rats would produce antibodies and show specificity for morphine or other heroin metabolites. The functional effects of the vaccine were tested with antinociceptive and conditioned place preference (CPP) tests. Rats were either vaccinated with KLH-6-SM and received two boosts 3 and 16 weeks later or served as controls and received KLH alone. Anti-morphine antibodies were produced in vaccinated rats; levels increased and were sustained at moderate levels through 24 weeks. Antibody binding was inhibited by free morphine and other heroin metabolites as demonstrated by competitive inhibition ELISA. Vaccinated rats showed reduced morphine CPP, tested during weeks 4 to 6, and decreased antinociceptive responses to morphine, tested at week 7. Brain morphine levels, assessed using gas-chromatography coupled to mass spectrometry (GC-MS) on samples obtained at 26 weeks, were significantly lower in vaccinated rats. This suggests that morphine entry into the brain was reduced or slowed. These results provide support for KLH-6-SM as a candidate vaccine for opioid dependence. (C) 2013 Elsevier Inc. All rights reserved. C1 [Shen, Xiaoyun Y.; O'Malley, Patrick W.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kosten, Therese A.; Shen, Xiaoyun Y.; Kinsey, Berma M.; Orson, Frank M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Orson, Frank M.; Kosten, Thomas R.] Michael E Debakey Vet Med Affairs Ctr, Houston, TX USA. [Lykissa, Ernest D.] ExperTox, Houston, TX USA. RP Kosten, TA (reprint author), Menninger Dept Psychiat & Behav Sci, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tkosten@bcm.edu FU National Institute on Drug Abuse [DA026859]; VA Merit Review Program FX Financial support was provided by a grant from the National Institute on Drug Abuse, DA026859, and by a grant from the VA Merit Review Program. The authors gratefully acknowledge the excellent technical assistance provided by A. Lopez and Y. Wu and thank Dr. Reetakshi Arora for her valuable input. NR 34 TC 10 Z9 10 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD AUG 1 PY 2013 VL 45 BP 223 EP 229 DI 10.1016/j.pnpbp.2013.05.012 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 202RW UT WOS:000323238300030 PM 23739535 ER PT J AU Bianchi, MT Thomas, RJ AF Bianchi, Matt T. Thomas, Robert J. TI Technical advances in the characterization of the complexity of sleep and sleep disorders SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Article DE Actigraphy; Autonomic; Cardiopulmonary coupling; Complex system; Hypnogram; Polysomnography; Sleep ID TRANSCRANIAL MAGNETIC STIMULATION; ELECTROCARDIOGRAM-BASED TECHNIQUE; PERIPHERAL ARTERIAL TONOMETRY; WORLD NETWORK ORGANIZATION; ALTERNATING PATTERN CAP; SLOW-WAVE ACTIVITY; FUNCTIONAL CONNECTIVITY; AMBULATORY DEVICE; NEURONAL-ACTIVITY; WAKE TRANSITIONS AB The current clinical standard for quantifying sleep physiology is the laboratory polysomnogram, from which basic sleep-wake stages are determined. However, the complexity of sleep physiology has inspired alternative metrics that are providing additional insights into the rich dynamics of sleep. Electro-encephalography, magneto-encephalography, and functional magnetic resonance imaging represent advanced imaging modalities for understanding brain dynamics. These methods are complemented by autonomic measurements that provide additional important insights. We review here the spectrum of approaches that have been leveraged towards improved understanding of the complexity of sleep. (C) 2012 Elsevier Inc. All rights reserved. C1 [Bianchi, Matt T.] Massachusetts Gen Hosp, Sleep Div, Dept Neurol, Boston, MA 02114 USA. [Thomas, Robert J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. RP Thomas, RJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, KB-023,330 Brookline Ave, Boston, MA 02215 USA. EM mtbianchi@partners.org; rthomas1@bidmc.harvard.edu FU NHLBI NIH HHS [RC1 HL099749] NR 81 TC 6 Z9 6 U1 0 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 EI 1878-4216 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD AUG 1 PY 2013 VL 45 BP 277 EP 286 DI 10.1016/j.pnpbp.2012.09.017 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 202RW UT WOS:000323238300038 PM 23174482 ER PT J AU Carmody, TP Duncan, CL Huggins, J Solkowitz, SN Lee, SK Reyes, N Mozgai, S Simon, JA AF Carmody, Timothy P. Duncan, Carol L. Huggins, Joy Solkowitz, Sharon N. Lee, Sharon K. Reyes, Norma Mozgai, Sharon Simon, Joel A. TI Telephone-Delivered Cognitive-Behavioral Therapy for Pain Management Among Older Military Veterans: A Randomized Trial SO PSYCHOLOGICAL SERVICES LA English DT Article DE pain; chronic pain; cognitive-behavioral therapy; pain management; telemen health ID LOW-BACK-PAIN; LUMBAR INSTRUMENTED FUSION; PRIMARY-CARE; PSYCHOLOGICAL INTERVENTIONS; ADMINISTERED PSYCHOTHERAPY; PSYCHOMETRIC PROPERTIES; DEPRESSION TREATMENT; COST-EFFECTIVENESS; CLINICAL-TRIAL; HEALTH-CARE AB This study investigated the effectiveness of telephone-delivered cognitive-behavioral therapy (T-CBT) in the management of chronic pain with older military veterans enrolled in VA primary-care clinics. We conducted a randomized clinical trial comparing T-CBT with telephone-delivered pain education (T-EDU). A total of 98 military veterans with chronic pain were enrolled in the study and randomized into one of two treatment conditions. Study participants were recruited from primary-care clinics at an urban VA medical center and affiliated VA community-based outpatient clinics (CBOCs). Pain management outcomes were measured at midtreatment (10 weeks), posttreatment (20 weeks), 3-month follow-up (32 weeks), and 6-month follow-up (46 weeks). No significant differences were found between the two treatment groups on any of the outcome measures. Both treatment groups reported small but significant increases in level of physical and mental health, and reductions in pain and depressive symptoms. Improvements in all primary outcome measures were mediated by reductions in catastrophizing. Telephone-delivered CBT and EDU warrant further study as easily accessible interventions for rural-living older individuals with chronic pain. C1 [Carmody, Timothy P.; Duncan, Carol L.; Huggins, Joy; Solkowitz, Sharon N.; Lee, Sharon K.; Reyes, Norma; Mozgai, Sharon; Simon, Joel A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Carmody, Timothy P.; Duncan, Carol L.; Huggins, Joy; Solkowitz, Sharon N.; Lee, Sharon K.; Reyes, Norma; Mozgai, Sharon] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Simon, Joel A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Simon, Joel A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Carmody, TP (reprint author), VA Med Ctr, 116B,4150 Clement St, San Francisco, CA 94121 USA. EM timothy.carmody@va.gov NR 57 TC 8 Z9 8 U1 3 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD AUG PY 2013 VL 10 IS 3 SI SI BP 265 EP 275 DI 10.1037/a0030944 PG 11 WC Psychology, Clinical SC Psychology GA 198HX UT WOS:000322914400001 PM 23244028 ER PT J AU Santa Ana, EJ Stallings, DL Rounsaville, BJ Martino, S AF Santa Ana, Elizabeth J. Stallings, Deidre L. Rounsaville, Bruce J. Martino, Steve TI Development of an In-Home Telehealth Program for Outpatient Veterans With Substance Use Disorders SO PSYCHOLOGICAL SERVICES LA English DT Article DE telepsychiatry; home telehealth; care coordination home telehealth; substance abuse treatment; treatment barriers ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; ALCOHOL DEPENDENCE; CARE; TELEPSYCHIATRY; INTERVENTION; TECHNOLOGY; MANAGEMENT; ADDICTION AB A variety of obstacles (e.g., lack of transportation, less availability of treatment in rural districts) contribute to underutilization of treatment among patients with substance use disorders, warranting the need to develop innovative strategies for enhancing access to treatment for these patients. The telehealth in-home-messaging-device is a small message-delivering and monitoring device connected via landline phone to a secure server that provides assessment and disease self-management education to patients in their homes. We describe the development of a Substance Use Disorder telehealth management program (SUD program) for use on this device and a feasibility pilot of the program with six outpatient veterans with substance use disorders referred by their primary medical care providers. These patients indicated that the SUD program was acceptable, easy to use, and helpful toward addressing their substance use problems. Home telehealth technology may be an innovative and feasible approach for providing substance abuse evidence-based treatment either as an adjunct to specialty treatment for substance use disorders or as a stand-alone intervention within primary care for a larger number of patients who may otherwise not access traditional treatment services. C1 [Santa Ana, Elizabeth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Neurosci, Charleston, SC 29401 USA. [Santa Ana, Elizabeth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Stallings, Deidre L.] VHA Off Telehlth Serv, Sunshine Training Ctr 08A, Lake City, FL USA. Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. VA CT Healthcare Syst, West Haven, CT USA. RP Santa Ana, EJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 109 Bee St, Charleston, SC 29401 USA. EM santaana@musc.edu NR 36 TC 2 Z9 2 U1 1 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD AUG PY 2013 VL 10 IS 3 SI SI BP 304 EP 314 DI 10.1037/a0026511 PG 11 WC Psychology, Clinical SC Psychology GA 198HX UT WOS:000322914400007 PM 23937090 ER PT J AU Baker, RR AF Baker, Rodney R. TI The History of the Division of Psychologists in Public Service (1946-2006) SO PSYCHOLOGICAL SERVICES LA English DT Article DE public service psychology; history of Division 18; history of APA; history of psychology AB The 60-year history of the American Psychological Association (APA) Division of Psychologists in Public Service (Division 18) is described. Included are relevant events in the history of the APA that led to the establishment of the division and later events within the APA that influenced the development and activities of the division. C1 [Baker, Rodney R.] Dept Vet Affairs, San Antonio, TX USA. RP Baker, RR (reprint author), 10710 Old Blue Lane, San Antonio, TX 78230 USA. EM rodbaker@att.net NR 7 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD AUG PY 2013 VL 10 IS 3 SI SI BP 353 EP 358 DI 10.1037/a0031598 PG 6 WC Psychology, Clinical SC Psychology GA 198HX UT WOS:000322914400013 PM 23398088 ER PT J AU Pape, TLB Guernon, A Lundgren, S Patil, V Herrold, AA Smith, B Blahnik, M Picon, LM Harton, B Peterson, M Mallinson, T Hoffmann, M AF Pape, Theresa Louise-Bender Guernon, Ann Lundgren, Sandra Patil, Vijaya Herrold, Amy A. Smith, Bridget Blahnik, Melanie Picon, Linda M. Harton, Brett Peterson, Michelle Mallinson, Trudy Hoffmann, Michael TI Predicting Levels of Independence With Expressing Needs and Ideas 1 Year After Severe Brain Injury SO REHABILITATION PSYCHOLOGY LA English DT Article DE prognoses; communication; coma; vegetative state; minimally conscious state ID SEVERE HEAD-INJURY; VEGETATIVE STATE; MEDICAL REHABILITATION; CONSCIOUSNESS SCALE; FAMILY CAREGIVERS; SUPPORT NEEDS; DISORDERS; RECOVERY; COMA; PROGNOSIS AB Purpose/Objective: Severe brain injury (BI) is a catastrophic event often evolving into a complex chronic and severely disabling condition making activity participation possible only with sustained caregiving. One aspect of building sustainable caregiving is early provision of information about expected outcomes germane to patients and their caregivers. An analysis was conducted to determine whether 2 levels of independence with expressing needs and ideas 1-year after severe BI could be predicted using variables available early after injury. Method: The authors examined a subsample (n = 79) of participants of an outcome study who received repeated neurobehavioral evaluations with the Disorders of Consciousness Scale (DOCS) and who were assessed 1 year after injury with the Functional Independence Measures (FM). Explanatory variables included DOCS measures, patient characteristics, coexisting conditions, and interventions. The outcome is measured with the FIM Expression item. Optimal data analysis was used to construct multivariate classification tree models. Results: The 2nd (p = .004) DOCS visual measure and seizure (p = .004) entered the final model providing 79% accuracy in classifying more or less independence with expressing needs and ideas at 1 year. The model will correctly identify 78% of future severe BI survivors who will have more independence and 82% of persons who will have less independence. Conclusions: For persons incurring severe BI, it is possible to predict, early after injury, C1 [Pape, Theresa Louise-Bender; Herrold, Amy A.; Smith, Bridget; Harton, Brett] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender; Herrold, Amy A.; Harton, Brett] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care Ctr Excellence, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender] Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Evanston, IL 60208 USA. [Guernon, Ann] Marianjoy Rehabil Hosp, Res Dept, Wheaton, IL USA. [Lundgren, Sandra] Minneapolis VA Hlth Care Syst, Psychol Serv, Minneapolis, MN USA. [Patil, Vijaya; Hoffmann, Michael] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. [Patil, Vijaya; Smith, Bridget] Loyola Univ Chicago, Stritch Sch Med, Dept Neurol, Chicago, IL USA. [Picon, Linda M.] James A Haley Vet Hosp, Audiol & Speech Pathol Serv, Tampa, FL 33612 USA. [Picon, Linda M.] Univ S Florida, Dept Commun Sci & Disorders, Tampa, FL 33620 USA. [Mallinson, Trudy] Univ So Calif, Div Occupat Sci & Occupat Therapy, Los Angeles, CA 90089 USA. RP Pape, TLB (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, POB 5000,M-C 151H, Hines, IL 60141 USA. EM theresa.pape@va.gov OI Pape, Theresa/0000-0001-7738-5963; Mallinson, Trudy/0000-0002-4888-5579 NR 51 TC 3 Z9 3 U1 0 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD AUG PY 2013 VL 58 IS 3 BP 253 EP 262 DI 10.1037/a0032610 PG 10 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 204ZB UT WOS:000323408700004 PM 23978083 ER PT J AU Schoenfeld, SR Kasturi, S Costenbader, KH AF Schoenfeld, Sara R. Kasturi, Shanthini Costenbader, Karen H. TI The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: A systematic review SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE Systemic lupus erythematosus; Atherosclerosis; Cardiovascular; Coronary artery disease; Myocardial infarction; Epidemiology; Risk factors; Cohort study; Risk ID CORONARY-ARTERY-DISEASE; MULTIETHNIC US COHORT; LUPUS-ERYTHEMATOSUS DATA; CONFER INCREASED RISK; MYOCARDIAL-INFARCTION; VASCULAR EVENTS; RHEUMATOID-ARTHRITIS; HEART-DISEASE; WOMEN; LUMINA AB Objective: To perform a systematic review of the literature regarding the epidemiology of the association between systemic lupus erythematosus (SLE) and atherosclerotic cardiovascular disease (CVD), including the increased risk for CVD, as well as the risk factors responsible for development of CVD in patients with SLE. Methods: We followed the PRISMA guidelines to systematically search the PubMed database from inception to June 2012. Studies were selected using predefined eligibility criteria, and 2 authors independently extracted data. The risk of bias was measured for each study using a domain-based assessment. Results: We report on 28 studies that met criteria for inclusion in our analysis. We found strong epidemiologic evidence that SLE patients have an increased relative risk of CVD compared to controls. There is limited information regarding relative CVD mortality risks among SLE patients. Traditional CVD risk factors, including age, male sex, hyperlipidemia, smoking, hypertension, and CRP, are associated with CVD risk among SLE patients. Several SLE-specific factors, including disease activity and duration, and possibly specific manifestations and therapies, further increase risk. Several risk factors, such as disease activity and glucocorticoid use, are closely associated, making it difficult to disentangle their effects. Conclusions: CVD risk among SLE patients compared to the general population is at least doubled. While older SLE patients appear to have the highest absolute risks of CVD, young women have alarmingly high relative risks, given the rarity of CVD in the comparison general population. Both traditional and SLE-specific risk factors are important, although there are discrepancies within the literature. (C) 2013 Elsevier Inc. All rights reserved. C1 [Schoenfeld, Sara R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kasturi, Shanthini] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Costenbader, Karen H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02115 USA. RP Costenbader, KH (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. EM KCostenbader@partners.org NR 47 TC 51 Z9 51 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD AUG PY 2013 VL 43 IS 1 BP 77 EP 95 DI 10.1016/j.semarthrit.2012.12.002 PG 19 WC Rheumatology SC Rheumatology GA 202SB UT WOS:000323238800010 PM 23422269 ER PT J AU Martinez-Quintanilla, J Bhere, D Heidari, P He, D Mahmood, U Shah, K AF Martinez-Quintanilla, Jordi Bhere, Deepak Heidari, Pedram He, Derek Mahmood, Umar Shah, Khalid TI Therapeutic Efficacy and Fate of Bimodal Engineered Stem Cells in Malignant Brain Tumors SO STEM CELLS LA English DT Article DE Stem cells; Herpes simplex virus thymidine kinase; Glioblastoma multiforme; In vivo imaging; Tumor necrosis factor apoptosis-inducing ligand ID POSITRON-EMISSION-TOMOGRAPHY; CANCER GENE-THERAPY; GROWTH IN-VIVO; SUICIDE GENE; GLIOMA MODEL; HEPATOCELLULAR-CARCINOMA; MONOCLONAL-ANTIBODY; EXPRESSION; TRAIL; MAPATUMUMAB AB Therapeutically engineered stem cells (SC) are emerging as an effective tumor-targeted approach for different cancer types. However, the assessment of the long-term fate of therapeutic SC post-tumor treatment is critical if such promising therapies are to be translated into clinical practice. In this study, we have developed an efficient SC-based therapeutic strategy that simultaneously allows killing of tumor cells and assessment and eradication of SC after treatment of highly malignant glioblastoma multiforme (GBM). Mesenchymal stem cells (MSC) engineered to co-express the prodrug converting enzyme, herpes simplex virus thymidine kinase (HSV-TK) and a potent and secretable variant of tumor necrosis factor apoptosis-inducing ligand (S-TRAIL) induced caspase-mediated GBM cell death and showed selective MSC sensitization to the prodrug ganciclovir (GCV). A significant decrease in tumor growth and a subsequent increase in survival were observed when mice bearing highly aggressive GBM were treated with MSC coexpressing S-TRAIL and HSV-TK. Furthermore, the systemic administration of GCV post-tumor treatment selectively eliminated therapeutic MSC expressing HSV-TK in vitro and in vivo, which was monitored in real time by positron emission-computed tomography imaging using 18F-FHBG, a substrate for HSV-TK. These findings demonstrate the development and validation of a novel therapeutic strategy that has implications in translating SC-based therapies in cancer patients. STEM Cells2013;31:1706-1714 C1 [Martinez-Quintanilla, Jordi; Bhere, Deepak; He, Derek; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Martinez-Quintanilla, Jordi; Bhere, Deepak; Heidari, Pedram; He, Derek; Mahmood, Umar; Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Heidari, Pedram; Mahmood, Umar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM kshah@mgh.harvard.edu FU American Cancer Society; James McDonald Foundation; [RO1 CA138922]; [RO1 NS071197]; [R01 CA173077] FX We thank Alicia Leece for the synthesis of 18F-FHBG used in this study. This work was supported by RO1 CA138922 (K. S.), RO1 NS071197 (K. S.), R01 CA173077 (K. S.), American Cancer Society (K. S.), and James McDonald Foundation (K.S.). NR 47 TC 26 Z9 27 U1 0 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD AUG PY 2013 VL 31 IS 8 BP 1706 EP 1714 DI 10.1002/stem.1355 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 205CM UT WOS:000323418700023 PM 23389839 ER PT J AU Graham, DB Xavier, RJ AF Graham, Daniel B. Xavier, Ramnik J. TI From genetics of inflammatory bowel disease towards mechanistic insights SO TRENDS IN IMMUNOLOGY LA English DT Review DE inflammatory bowel disease (IBD); Crohn's disease; ulcerative colitis; genome-wide association study (GWAS); genomics; mucosal immunity; host defense ID GENOME-WIDE ASSOCIATION; NATURAL-KILLER-CELLS; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; INTESTINAL INFLAMMATION; INFLAMED MUCOSA; NONCODING RNAS; CUTTING EDGE; T-CELLS; B-CELLS AB Advancements in human genetics now poise the field to illuminate the pathophysiology of complex genetic disease. In particular, genome-wide association studies (GWAS) have generated insights into the mechanisms driving inflammatory bowel disease (IBD) and implicated genes shared by multiple autoimmune and autoinflammatory diseases. Thus, emerging evidence suggests a central role for the mucosal immune system in mediating immune homeostasis and highlights the complexity of genetic and environmental interactions that collectively modulate the risk of disease. Nevertheless, the challenge remains to determine how genetic variation can precipitate and sustain the inappropriate inflammatory response to commensals that is observed in IBD. Here, we highlight recent advancements in immunogenetics and provide a forward-looking view of the innovations that will deliver mechanistic insights from human genetics. C1 [Graham, Daniel B.; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Graham, Daniel B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Graham, DB (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM dgraham@broadinstitute.org FU Center for the Study of Inflammatory Bowel Diseases (Massachusetts General Hospital); Helmsley Trust; NIH [R01 DK092405] FX The authors are funded by the Center for the Study of Inflammatory Bowel Diseases (Massachusetts General Hospital), the Helmsley Trust, and NIH R01 DK092405. NR 92 TC 37 Z9 39 U1 2 U2 25 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD AUG PY 2013 VL 34 IS 8 BP 371 EP 378 DI 10.1016/j.it.2013.04.001 PG 8 WC Immunology SC Immunology GA 207JJ UT WOS:000323594400002 PM 23639549 ER PT J AU Byrne, T Montgomery, AE Dichter, ME AF Byrne, Thomas Montgomery, Ann Elizabeth Dichter, Melissa E. TI Homelessness Among Female Veterans: A Systematic Review of the Literature SO WOMEN & HEALTH LA English DT Review DE homelessness; women; veterans; systematic review ID HEALTH-CARE UTILIZATION; WOMEN VETERANS; GENDER-DIFFERENCES; MENTAL-HEALTH; CLINICAL-OUTCOMES; SUBSTANCE-ABUSERS; PREDICTORS; PROGRAM; ILLNESS; DETERMINANTS AB The authors conducted a systematic, critical review of the literature to assess and summarize existing research on homelessness among female veterans. They searched seven electronic databases (ERIC, Proquest Dissertations and Theses, PsycINFO, PubMed, Social Services Abstracts, Social Science Citation Index, and Sociological Abstracts), websites of several government and research organizations, and reference lists of prior studies. They abstracted data on study design, funding source, and topic from studies meeting inclusion criteria and classified each study into one of the following categories: epidemiology, health and other services utilization, and interventions. The authors included both experimental and observational studies of interventions in the review and performed a narrative synthesis for each of the 26 studies identified. No studies were experimental, 20 were observational, and the remainder were either qualitative or descriptive. Of the 26 identified studies, 14 were epidemiologic, 7 focused on the health and additional service utilization, and 5 were intervention studies. Findings provided important baseline epidemiologic information about homelessness among female veterans and indicated that female veterans were at an increased risk of homelessness relative to their male veteran and female non-veteran counterparts. Additional research is needed to develop and implement effective, evidence-based programs to prevent and end homelessness among women veterans. C1 [Byrne, Thomas; Montgomery, Ann Elizabeth] Natl Ctr Homelessness Vet, Philadelphia, PA 19104 USA. [Byrne, Thomas] Univ Penn, Philadelphia, PA 19104 USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, CHERP, Philadelphia, PA USA. RP Byrne, T (reprint author), Natl Ctr Homelessness Vet, 4100 Chester Ave,Suite 201, Philadelphia, PA 19104 USA. EM byrnet@sp2.upenn.edu NR 56 TC 5 Z9 5 U1 3 U2 22 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0363-0242 J9 WOMEN HEALTH JI Women Health PD AUG 1 PY 2013 VL 53 IS 6 BP 572 EP 596 DI 10.1080/03630242.2013.817504 PG 25 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 199WF UT WOS:000323025500003 PM 23937730 ER PT J AU Pompili, M Serafini, G Innamorati, M Venturini, P Fusar-Poli, P Sher, L Amore, M Girardi, P AF Pompili, Maurizio Serafini, Gianluca Innamorati, Marco Venturini, Paola Fusar-Poli, Paolo Sher, Leo Amore, Mario Girardi, Paolo TI Agomelatine, a novel intriguing antidepressant option enhancing neuroplasticity: A critical review SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Review DE Agomelatine; antidepressant drugs; efficacy; tolerability; neuroplasticity ID MAJOR DEPRESSIVE DISORDER; 5HT(2C) RECEPTORS ANTAGONIST; PLACEBO-CONTROLLED-TRIAL; DOUBLE-BLIND; MELATONIN RECEPTORS; NEUROTROPHIC FACTOR; MESSENGER-RNA; HIPPOCAMPAL NEUROGENESIS; NEURONAL PLASTICITY; CELLULAR RESILIENCE AB Objectives. The treatment of major affective disorders, commonly associated with high disability and elevated social costs may be still considered unsatisfactory. Among all antidepressant drugs, predominantly acting through monoaminergic mechanisms, agomelatine is of particular interest due to another alternative mechanism of action. Targeting melatonergic receptors, agomelatine play a crucial role in synchronizing circadian rhythms, known to be altered in depressed subjects. Methods. A critical review of the literature focusing on efficacy, safety and tolerability of agomelatine in major affective disorders was performed. Additionally, we focused on the potential of agomelatine in enhancing neuroplasticity mechanisms and promote neurogenesis. A total of 136 articles from peer-reviewed journals were identified, of which 50 were assessed for eligibility and 21 were included. Results. Agomelatine, a melatonergic analogue drug acting as MT1/MT2 agonist and 5-HT2C antagonist, has been reported to be effective as antidepressant drug. Studies confirmed not only clinical efficacy but also safety and tolerability of agomelatine. Also, it enhances neuroplasticity mechanisms and adult neurogenesis in brain areas such as hippocampus and prefrontal cortex. Conclusions. Agomelatine actually represents an intriguing option in the treatment of affective disorders. C1 [Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Venturini, Paola; Girardi, Paolo] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs, St Andrea Hosp, I-00189 Rome, Italy. [Fusar-Poli, Paolo] Inst Psychiat, Dept Psychosis Studies, London, England. [Sher, Leo] Mt Sinai Sch Med, James J Peters Vet Adm Med Ctr, Dept Psychiat, Bronx, NY USA. [Amore, Mario] Univ Genoa, Sect Psychiat, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs, St Andrea Hosp, Suicide Prevent Ctr, Via Grottarossa 1035-1039, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it; gianluca.serafini@uniroma1.it OI Innamorati, Marco/0000-0003-1389-2290; Pompili, Maurizio/0000-0003-1886-4977 NR 101 TC 26 Z9 27 U1 2 U2 8 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 AUG PY 2013 VL 14 IS 6 BP 412 EP 431 DI 10.3109/15622975.2013.765593 PG 20 WC Psychiatry SC Psychiatry GA 206CM UT WOS:000323494100002 PM 23530731 ER PT J AU Sainani, NI Arellano, RS Shyn, PB Gervais, DA Mueller, PR Silverman, SG AF Sainani, Nisha I. Arellano, Ronald S. Shyn, Paul B. Gervais, Debra A. Mueller, Peter R. Silverman, Stuart G. TI The challenging image-guided abdominal mass biopsy: established and emerging techniques 'if you can see it, you can biopsy it' SO ABDOMINAL IMAGING LA English DT Review DE Image-guided; Biopsy; Abdominal; Percutaneous; Challenging ID NEEDLE ASPIRATION BIOPSY; TECHNICALLY EASY APPROACH; CT FLUOROSCOPY; PERCUTANEOUS BIOPSY; ADRENAL BIOPSY; DIAGNOSTIC-ACCURACY; INITIAL-EXPERIENCE; UPPER ABDOMEN; LIVER; LESIONS AB Image-guided percutaneous biopsy of abdominal masses is among the most commonly performed procedures in interventional radiology. While most abdominal masses are readily amenable to percutaneous biopsy, some may be technically challenging for a number of reasons. Low lesion conspicuity, small size, overlying or intervening structures, motion, such as that due to respiration, are some of the factors that can influence the ability and ultimately the success of an abdominal biopsy. Various techniques or technologies, such as choice of imaging modality, use of intravenous contrast and anatomic landmarks, patient positioning, organ displacement or trans-organ approach, angling CT gantry, triangulation method, real-time guidance with CT fluoroscopy or ultrasound, sedation or breath-hold, pre-procedural image fusion, electromagnetic tracking, and others, when used singularly or in combination, can overcome these challenges to facilitate needle placement in abdominal masses that otherwise would be considered not amenable to percutaneous biopsy. Familiarity and awareness of these techniques allows the interventional radiologist to expand the use of percutaneous biopsy in clinical practice, and help choose the most appropriate technique for a particular patient. C1 [Sainani, Nisha I.; Shyn, Paul B.; Silverman, Stuart G.] Brigham & Womens Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. [Arellano, Ronald S.; Gervais, Debra A.; Mueller, Peter R.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sainani, NI (reprint author), Brigham & Womens Hosp, Div Abdominal Imaging & Intervent, 75 Francis St, Boston, MA 02115 USA. EM nsainani@partners.org NR 47 TC 16 Z9 16 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2013 VL 38 IS 4 BP 672 EP 696 DI 10.1007/s00261-013-9980-0 PG 25 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 200FE UT WOS:000323052400004 PM 23381506 ER PT J AU Quencer, KB Nimkin, K Mino-Kenudson, M Gee, MS AF Quencer, Keith B. Nimkin, Katherine Mino-Kenudson, Mari Gee, Michael S. TI Detecting active inflammation and fibrosis in pediatric Crohn's disease: prospective evaluation of MR-E and CT-E SO ABDOMINAL IMAGING LA English DT Article DE Crohn's disease; Fibrosis; MR enterography (MR-E); CT enterography (CT-E) ID BOWEL-DISEASE; INTESTINAL FIBROSIS; ENTEROGRAPHY; RADIATION; EXPOSURE; PATIENT; RISKS AB Symptoms of Crohn's disease (CD) can be due to active inflammation or fibrosis. Differentiating these based on clinical presentation, endoscopy, laboratory parameters, and clinical scoring methods can be inaccurate and/or invasive. As therapy decisions are often directed based on whether active disease or fibrosis is present, a reliable and non-invasive test to distinguish these two etiologies would be a powerful clinical tool. CT enterography (CT-E) and MR enterography (MR-E) are two non-invasive imaging modalities tailored to evaluate the small bowel. The purpose of our study was to compare the ability of MR-E and CT-E to assess for active inflammation and mural fibrosis in patients with known CD as compared to a histologic reference standard. After obtaining MR-E and CT-E on the same day, a total of 61 histologic samples were obtained from twelve subjects aged 12-20 years via full-thickness bowel resection or endoscopy. These were evaluated by the pathologist for active inflammation and fibrosis. We found that while CT-E and MR-E were similar in their accuracies of depicting active inflammation, MR-E was significantly more sensitive in detecting fibrosis. Because of this and the lack of ionizing radiation from MR-E, we believe that MR-E rather than CT-E should serve as the primary imaging modality for the assessment of CD pediatric patients with non-acute clinical exacerbations. C1 [Quencer, Keith B.; Nimkin, Katherine; Mino-Kenudson, Mari; Gee, Michael S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Quencer, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM kquencer@partners.org FU Harvard Medical School [UL1 RR025758-02]; National Institutes of Health FX Supported by a Clinical and Translational Science Award UL1 RR025758-02 (to M.S.G.) from Harvard Medical School and the National Institutes of Health. NR 26 TC 26 Z9 27 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2013 VL 38 IS 4 BP 705 EP 713 DI 10.1007/s00261-013-9981-z PG 9 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 200FE UT WOS:000323052400006 PM 23361877 ER PT J AU Oliva, IB Davarpanah, AH Rybicki, FJ Desjardins, B Flamm, SD Francois, CJ Gerhard-Herman, MD Kalva, SP Mansour, MA Mohler, ER Schenker, MP Weiss, C Dill, KE AF Oliva, Isabel B. Davarpanah, Amir H. Rybicki, Frank J. Desjardins, Benoit Flamm, Scott D. Francois, Christopher J. Gerhard-Herman, Marie D. Kalva, Sanjeeva P. Mansour, M. Ashraf Mohler, Emile R., III Schenker, Matthew P. Weiss, Clifford Dill, Karin E. TI ACR appropriateness criteria((R)) imaging of mesenteric ischemia SO ABDOMINAL IMAGING LA English DT Article DE Appropriateness criteria; Mesenteric ischemia; Acute abdomen; Abdominal pain; Bowel ischemia ID ACUTE BOWEL ISCHEMIA; INTESTINAL ISCHEMIA; ENDOVASCULAR TREATMENT; CT ANGIOGRAPHY; DUPLEX ULTRASOUND; MR-ANGIOGRAPHY; PLAIN FILM; DIAGNOSIS; OCCLUSION; CONTRAST AB Mesenteric ischemia is a rare disease associated with high morbidity and mortality. Acute mesenteric ischemia is most commonly secondary to embolism followed by arterial thrombosis, nonocclusive ischemia, and less commonly venous thrombosis. Chronic mesenteric ischemia is almost always caused by atherosclerotic disease, with rare causes including fibromuscular dysplasia and vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Patients with mesenteric ischemia usually present with nonspecific abdominal symptoms and laboratory findings. This document evaluates and rates the appropriateness of imaging to evaluate patients with clinically suspected mesenteric ischemia. While catheter-based angiography has been considered the reference standard and enables diagnosis and treatment, advances in computed tomography have made it a first-line test in many patients because it is a fast, widely available, and noninvasive study. Abdominal radiographs and ultrasound have a limited role in diagnosing mesenteric ischemia but are commonly the first ordered tests in patients with abdominal pain and may diagnose more common pathologies. C1 [Oliva, Isabel B.; Davarpanah, Amir H.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Rybicki, Frank J.; Gerhard-Herman, Marie D.; Schenker, Matthew P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Desjardins, Benoit; Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA. [Flamm, Scott D.] Cleveland Clin, Cleveland, OH 44106 USA. [Francois, Christopher J.] Univ Wisconsin, Madison, WI USA. [Mohler, Emile R., III] Amer Coll Cardiol, Washington, DC USA. [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mansour, M. Ashraf] Vasc Associates, Grand Rapids, MI USA. [Mansour, M. Ashraf] Soc Vasc Surg, Chicago, IL USA. [Weiss, Clifford] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Dill, Karin E.] Univ Chicago, Chicago, IL 60637 USA. RP Oliva, IB (reprint author), Yale Univ, Sch Med, New Haven, CT 06520 USA. EM isabel.oliva@yale.edu NR 33 TC 23 Z9 24 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2013 VL 38 IS 4 BP 714 EP 719 DI 10.1007/s00261-012-9975-2 PG 6 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 200FE UT WOS:000323052400007 PM 23296712 ER PT J AU Saboo, SS Zukotynski, K Shinagare, AB Krajewski, KM Ramaiya, N AF Saboo, Sachin S. Zukotynski, Katherine Shinagare, Atul B. Krajewski, Katherine M. Ramaiya, Nikhil TI Anal carcinoma: FDG PET/CT in staging, response evaluation, and follow-up SO ABDOMINAL IMAGING LA English DT Article DE Anal carcinoma; F-18-FDG PET/CT; Diagnosis; Staging; Treatment monitoring ID POSITRON-EMISSION-TOMOGRAPHY; CANCER; GUIDELINES; MANAGEMENT; IMPACT AB The role of FDG PET/CT in anal cancer is becoming increasingly important. At the time of initial staging, FDG PET/CT can detect the primary site of disease more frequently than CT, is sensitive for nodal and metastatic spread and alters staging in a significant number of patients. Indeed, the NCCN guidelines for anal cancer published in April 2012 recommend FDG PET/CT for therapy planning. Metabolic activity of primary anal cancer at presentation is a potential biomarker for predicting prognosis, treatment response and survival. More intensely FDG-avid primary malignancy is associated with a higher incidence of disease spread. Metabolic response following chemoradiotherapy is associated with improved survival. The aim of this paper is to provide an up-to-date pictorial review of FDG PET/CT in anal cancer at the time of staging and to illustrate its utility for determining response to therapy and detecting recurrent disease. C1 [Saboo, Sachin S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Saboo, SS (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM ssaboo@partners.org NR 21 TC 10 Z9 10 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2013 VL 38 IS 4 BP 728 EP 735 DI 10.1007/s00261-012-9958-3 PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 200FE UT WOS:000323052400009 PM 23011550 ER PT J AU Gabayan, GZ Sun, BC Asch, SM Timmermans, S Sarkisian, C Yiu, S Lancaster, EM Poon, KT Kellermann, AL Ryan, G Miniel, NJ Flansbaum, D Hoffman, JR Derose, SF AF Gabayan, Gelareh Z. Sun, Benjamin C. Asch, Steven M. Timmermans, Stefan Sarkisian, Catherine Yiu, Sau Lancaster, Elizabeth M. Poon, K. Trudy Kellermann, Arthur L. Ryan, Gery Miniel, Nicholas J. Flansbaum, Drew Hoffman, Jerome R. Derose, Stephen F. TI Qualitative Factors in Patients Who Die Shortly After Emergency Department Discharge SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID DEATH AFTER-DISCHARGE; MEDICAL LITERATURE; USERS GUIDES; HEALTH-CARE; HOME; XXIII; FALLS; TIME AB Objectives Early death after emergency department (ED) discharge may signal opportunities to improve care. Prior studies are limited by incomplete mortality ascertainment and lack of clinically important information in administrative data. The goal in this hypothesis-generating study was to identify patient and process of care themes that may provide possible explanations for early postdischarge mortality. Methods This was a qualitative analysis of medical records of adult patients who visited the ED of any of six hospitals in an integrated health system (Kaiser Permanente Southern California [KPSC]) and died within 7days of discharge in 2007 and 2008. Nonmembers, visits to non-health plan hospitals, patients receiving or referred to hospice care, and patients with do not attempt resuscitation or do not intubate orders (DNAR/DNI) were excluded. Under the guidance of two qualitative research scientists, a team of three emergency physicians used grounded theory techniques to identify patient clinical presentations and processes of care that serve as potential explanations for poor outcome after discharge. Results The source population consisted of a total of 290,092 members with 446,120 discharges from six KPSC EDs in 2007 and 2008. A total of 203 deaths occurred within 7days of ED discharge (0.05%). Sixty-one randomly chosen cases were reviewed. Patient-level themes that emerged included an unexplained persistent acute change in mental status, recent fall, abnormal vital signs, ill-appearing presentation, malfunctioning indwelling device, and presenting symptoms remaining at discharge. Process-of-care factors included a discrepancy in history of present illness, incomplete physical examination, and change of discharge plan by a third party, such as a consulting or admitting physician. Conclusions In this hypothesis-generating study, qualitative research techniques were used to identify clinical and process-of-care factors in patients who died withindays after discharge from an ED. These potential predictors will be formally tested in a future quantitative study. (C) 2013 by the Society for Academic Emergency Medicine C1 [Gabayan, Gelareh Z.; Sarkisian, Catherine] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Timmermans, Stefan] Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.; Sarkisian, Catherine] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA. [Gabayan, Gelareh Z.; Lancaster, Elizabeth M.; Flansbaum, Drew; Hoffman, Jerome R.] Ronald Reagan UCLA, Ctr Emergency Med, Los Angeles, CA USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Asch, Steven M.] Stanford Sch Med, Dept Med, Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Yiu, Sau; Lancaster, Elizabeth M.; Poon, K. Trudy; Derose, Stephen F.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Kellermann, Arthur L.; Ryan, Gery] RAND Hlth, Santa Monica, CA USA. [Miniel, Nicholas J.; Flansbaum, Drew] Olive View UCLA Emergency Med Ctr, Sylmar, CA USA. RP Gabayan, GZ (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. EM Gelareh@gabayan.com FU Kaiser Permanente Southern California; Emergency Medicine Foundation Career Development Award [59668]; UCLA Oppenheimer Foundation; UCLA Older Americans Independence Center (NIH/NIA K) [P30-AG028748]; National Center for Advancing Translational Sciences [KL2TR000122] FX This research was supported by Kaiser Permanente Southern California. During the initial phase of the project, Dr. Gabayan received support from the Emergency Medicine Foundation Career Development Award (59668 G. Gabayan) and the UCLA Oppenheimer Foundation, and Dr. Sun received support from the UCLA Older Americans Independence Center (NIH/NIA K grant P30-AG028748). Continued support was obtained for Dr. Gabayan from the National Center for Advancing Translational Sciences, grant KL2TR000122. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the NIA. NR 25 TC 6 Z9 6 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 2013 VL 20 IS 8 BP 778 EP 785 DI 10.1111/acem.12181 PG 8 WC Emergency Medicine SC Emergency Medicine GA 201IQ UT WOS:000323134300005 PM 24033620 ER PT J AU Caterino, JM Sullivan, AF Betz, ME Espinola, JA Miller, I Camargo, CA Boudreaux, ED AF Caterino, Jeffrey M. Sullivan, Ashley F. Betz, Marian E. Espinola, Janice A. Miller, Ivan Camargo, Carlos A., Jr. Boudreaux, Edwin D. CA Emergency Dept Safety Assessment TI Evaluating Current Patterns of Assessment for Self-harm in Emergency Departments: A Multicenter Study SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID ATTEMPTED-SUICIDE; RISK RATIOS; VISITS; TRENDS; INJURY; ADULTS AB Objectives The objective was to describe self-harm assessment practices in U.S. emergency departments (EDs) and to identify predictors of being assessed. Methods This was a prospective observational cohort study of adults presenting to eight U.S. EDs. A convenience sample of adults presenting to the EDs during covered research shifts was entered into a study log. Self-harm assessment was defined as ED documentation of suicide attempt; suicidal ideation; or nonsuicidal self-injury thoughts, behaviors, or both. Institution characteristics were compared relative to percentage assessed. To identify predictive patient characteristics, multivariable generalized linear models were created controlling for weekend presentation, time of presentation, age, sex, and race and ethnicity. Results Among 94,354 charts, self-harm assessment ranged from 3.5% to 31%, except for one outlying site at 95%. Overall, 26% were assessed (11% excluding the outlying site). Current self-harm was present in 2.7% of charts. Sites with specific self-harm assessment policies had higher assessment rates. In the complete model, adjusted risk ratios (aRR) for assessment included age 65years (0.56, 95% confidence interval [CI]=0.35 to 0.92) and male sex (1.17, 95% CI=1.10 to 1.26). There was an interaction between these variables in the smaller model (excluding outlying site), with males<65years of age being more likely to be assessed (aRR= 1.14, 95% CI=1.02 to 1.37). Conclusions Emergency department assessment of self-harm was highly variable among institutions. Presence of specific assessment policies was associated with higher assessment rates. Assessment varied based upon patient characteristics. The identification of self-harm in 2.7% of ED patients indicates that a substantial proportion of current risk of self-harm may go unidentified, particularly in certain patient groups. (C) 2013 by the Society for Academic Emergency Medicine C1 [Caterino, Jeffrey M.] Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA. [Caterino, Jeffrey M.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Betz, Marian E.] Univ Colorado, Dept Emergency Med, Sch Med, Aurora, CO USA. [Miller, Ivan] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA. RP Caterino, JM (reprint author), Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA. EM jeffrey.caterino@osumc.edu OI Betz, Marian/0000-0003-1643-6565; Boudreaux, Edwin/0000-0002-3223-6371 FU National Institute of Mental Health [U01MH088278]; National Institute on Aging [1K23AG038351] FX This project was supported by Award U01MH088278 from the National Institute of Mental Health. Dr. Caterino's time was supported by Award 1K23AG038351 from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, National Institute on Aging, or the National Institutes of Health. The authors declare no conflicts of interest or disclosures. NR 28 TC 9 Z9 9 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 2013 VL 20 IS 8 BP 807 EP 815 DI 10.1111/acem.12188 PG 9 WC Emergency Medicine SC Emergency Medicine GA 201IQ UT WOS:000323134300009 PM 24033624 ER PT J AU Brunner, AM Sadrzadeh, H Feng, Y Drapkin, BJ Ballen, KK Attar, EC Amrein, PC McAfee, SL Chen, YB Neuberg, DS Fathi, AT AF Brunner, Andrew M. Sadrzadeh, Hossein Feng, Yang Drapkin, Benjamin J. Ballen, Karen K. Attar, Eyal C. Amrein, Philip C. McAfee, Steven L. Chen, Yi-Bin Neuberg, Donna S. Fathi, Amir T. TI Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID HEMATOPOIETIC-CELL TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; ADULT PATIENTS; SURFACE AREA; LEPTIN RECEPTOR; UNITED-STATES; EARLY DEATH; OBESITY; RISK; OVERWEIGHT AB Acute myeloid leukemia (AML) is more common and more lethal among patients over the age of 60. Increased body mass index (BMI) has been associated with a higher incidence of various malignancies, including AML. We sought to determine whether patient BMI at the time of AML diagnosis is related to overall survival (OS) among elderly patients. We identified 97 patients with AML diagnosed after the age of 60 and treated with cytarabine-based induction chemotherapy. The median age was 68 years (range 60-87); 52% of patients were male, and our study population was predominantly white (89% of patients). The median OS for all patients was 316 days (95% CI 246-459). The hazard ratio for mortality was increased among patients with a BMI < 25 compared to BMI 30 (HR 2.14, P = 0.009, 95% CI 1.21-3.77), as well as with older age (HR 1.76, P = 0.015, 95% CI 1.12-2.79) and with secondary versus de novo disease (HR 1.95, P = 0.006, 95% CI 1.21-3.14). After multivariable analysis, we did not find a significant association between OS and other potential confounders such as coronary artery disease or diabetes among these patients. We conclude that increased BMI was independently associated with improved OS among older AML patients at our institution. Am. J. Hematol. 88:642-646, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Brunner, Andrew M.; Sadrzadeh, Hossein; Drapkin, Benjamin J.; Ballen, Karen K.; Attar, Eyal C.; Amrein, Philip C.; McAfee, Steven L.; Chen, Yi-Bin; Fathi, Amir T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol & Oncol, Boston, MA USA. [Feng, Yang; Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Fathi, AT (reprint author), Massachusetts Gen Hosp, 0 Emerson Pl,Suite 118, Boston, MA 02114 USA. EM afathi@partners.org FU NCI NIH HHS [P30 CA006516] NR 44 TC 9 Z9 9 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 AUG PY 2013 VL 88 IS 8 BP 642 EP 646 DI 10.1002/ajh.23462 PG 5 WC Hematology SC Hematology GA 187ZO UT WOS:000322160900003 PM 23619915 ER PT J AU Ghosh, P Sahoo, R Vaidya, A Cantel, S Kavishwar, A Goldfine, A Herring, N Bry, L Chorev, M Halperin, JA AF Ghosh, Pamela Sahoo, Rupam Vaidya, Anand Cantel, Sonia Kavishwar, Amol Goldfine, Allison Herring, Neil Bry, Lynn Chorev, Michael Halperin, Jose A. TI A specific and sensitive assay for blood levels of glycated CD59: A novel biomarker for diabetes SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID TERMINAL COMPLEMENT COMPLEXES; REGULATORY PROTEIN CD59; VASCULAR COMPLICATIONS; ACTIVE-SITE; ACTIVATION; INHIBITOR; ANTIBODY; SYSTEM; LYSIS AB Increasing evidence links the complement system with complications of human diabetes. The complement regulatory protein CD59, an inhibitor of formation of membrane attack complex (MAC), is inhibited by hyperglycemia-induced glycation fostering increased deposition of MAC, a major effector of complement-mediated tissue damage. CD59, an ubiquitous GPI-anchored membrane protein, is shed from cell membranes by phospholipases generating a soluble form present in blood and urine. We established an enzyme-linked immunosorbent assay (ELISA) to measure serum/plasma glycated human CD59 (hCD59) (GCD59) and evaluated its potential as a diabetes biomarker. We used a synthetic peptide strategy to generate (a) a mouse monoclonal antibody to capture hCD59, (b) a rabbit monoclonal antibody to detect GCD59, and (c) a GCD59 surrogate for assay standardization. ELISA conditions were optimized for precision, reproducibility, and clinical sensitivity. The clinical utility of the assay was initially evaluated in 24 subjects with or without diabetes and further validated in a study that included 100 subjects with and 90 subjects without a diagnosis of diabetes. GCD59 (a) was significantly higher in individuals with than in individual without diabetes, (b) was independently associated with HbA1c, and (c) identified individuals with diabetes with high specificity and sensitivity. We report the development and standardization of a novel, sensitive, and specific ELISA for measuring GCD59 in blood. The assay distinguished individuals with diabetes from those without, and showed strong correlation between GCD59 and HbA1c. Because GCD59 likely contributes to the pathogenesis of diabetes complications, measurement of blood levels of GCD59 may be useful in the diagnosis and management of diabetes. Am. J. Hematol. 88:670-676, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Ghosh, Pamela; Sahoo, Rupam; Cantel, Sonia; Kavishwar, Amol; Chorev, Michael; Halperin, Jose A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA. [Vaidya, Anand; Goldfine, Allison] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Goldfine, Allison] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Herring, Neil; Bry, Lynn] Partners Healthcare Syst, Crimson Biospecimen Core, Boston, MA USA. RP Halperin, JA (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM jhalperin@partners.org RI SAHOO, RUPAM/B-3935-2016; OI Kavishwar, Amol/0000-0001-8214-6625 FU National Institutes of Health [DK62294, DK089206]; National Heart, Lung, and Blood Institute of the National Institutes of Health [K23HL111771] FX Contract grant sponsor: Jose A. Halperin; Contract grant number: National Institutes of Health Grants DK62294 and DK089206.; Contract grant sponsor: Anand Vaidya; Contract grant number: National Heart, Lung, and Blood Institute of the National Institutes of Health Grant K23HL111771. The content is solely the responsibility of the authors and does not necessarily represent the official views of National Institutes of Health. NR 37 TC 7 Z9 7 U1 3 U2 12 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 AUG PY 2013 VL 88 IS 8 BP 670 EP 676 DI 10.1002/ajh.23478 PG 7 WC Hematology SC Hematology GA 187ZO UT WOS:000322160900009 PM 23670858 ER PT J AU Peralta, CA Vittinghoff, E Bansal, N Jacobs, D Muntner, P Kestenbaum, B Lewis, C Siscovick, D Kramer, H Shlipak, M Bibbins-Domingo, K AF Peralta, Carmen A. Vittinghoff, Eric Bansal, Nisha Jacobs, David, Jr. Muntner, Paul Kestenbaum, Bryan Lewis, Cora Siscovick, David Kramer, Holly Shlipak, Michael Bibbins-Domingo, Kirsten TI Trajectories of Kidney Function Decline in Young Black and White Adults With Preserved GFR: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Trajectories; race; decline; kidney ID STAGE RENAL-DISEASE; SERUM CYSTATIN-C; SERIAL MEASUREMENTS; RACIAL-DIFFERENCES; UNITED-STATES; CREATININE; PROGRESSION; MORTALITY AB Background: Strong racial discrepancies in end-stage renal disease exist. Whether there are race differences in kidney function loss in younger healthy persons is not well established. Study Design: Longitudinal. Setting & Participants: 3,348 black and white adults with at least 2 measurements of cystatin C-based estimated glomerular filtration rate (eGFR(cys)) at scheduled Coronary Artery Risk Development in Young Adults (CARDIA) examinations (years 10, 15, and 20). Predictor: Race. Outcomes & Measurements: We used linear mixed models to examine race differences in annualized rates of eGFR(cys) decline, adjusting for age, sex, lifetime exposure to systolic blood pressure >120 mm Hg, diabetes, and albumin-creatinine ratio. We used Poisson regression to compare racial differences in rapid decline (eGFR(cys) decline >3% per year) by study period (10-15 years after baseline examination [defining period 1] and >15-20 years after baseline examination [defining period 2]). Results: Mean age was 35 +/- 3.6 (SD) years, and mean eGFR(cys) was 110 +/- 20 mL/min/1.73 m(2) for blacks and 104 +/- 17 mL/min/1.73 m(2) for whites at baseline. For both blacks and whites, eGFR(cys) decline was minimal at younger ages (<35 years) and eGFR(cys) loss accelerated at older ages. However, acceleration of eGFR(cys) decline occurred at earlier ages for blacks than whites. Blacks had somewhat faster annualized rates of decline compared with whites, but differences were attenuated after adjustment in period 1 (0.13 mL/min/1.73 m(2) per year faster; P = 0.2). In contrast, during period 2, blacks had significantly faster annualized rates of decline, even after adjustment (0.32 mL/min/1.73 m(2) per year faster; P = 0.003). The prevalence of rapid decline was significantly higher for blacks versus whites, with prevalence rate ratios of 1.31 (95% CI, 1.04-1.63) for period 1 and 1.24 (95% CI, 1.09-1.41) for period 2. Differences were attenuated after full adjustment: adjusted prevalence rate ratios were 1.20 (95% CI, 0.95-1.49) for period 1 and 1.10 (95% CI, 0.96-1.26) for period 2. Limitations: No measured GFR. Conclusions: eGFR(cys) decline differs by race at early ages, with faster annualized rates of decline for blacks. Future studies are required to explain the observed differences. (c) 2013 by the National Kidney Foundation, Inc. C1 [Peralta, Carmen A.; Vittinghoff, Eric; Bansal, Nisha; Shlipak, Michael; Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Peralta, Carmen A.; Shlipak, Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Jacobs, David, Jr.] Univ Minnesota, Minneapolis, MN USA. [Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL USA. [Kestenbaum, Bryan; Siscovick, David] Univ Washington, Washington, DC USA. [Kramer, Holly] Loyola Univ, Chicago, IL 60611 USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu OI Kramer, Holly/0000-0002-6374-837X FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1K23DK082793-01, R01DK078124]; Robert Wood Johnson Harold Amos Program; National Heart, Lung and Blood Institute (NHLBI) [N01HC48050]; National Institute on Minority Health and Health Disparities (NIMHD), Comprehensive Centers of Excellence [1P60MD006902]; NIDDK [P30-DK092924] FX Dr Peralta is funded by grant 1K23DK082793-01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Robert Wood Johnson Harold Amos Program. Dr Bibbins-Domingo was in part supported by grant R01DK078124 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), grant N01HC48050 from the National Heart, Lung and Blood Institute (NHLBI), from grant 1P60MD006902 from the National Institute on Minority Health and Health Disparities (NIMHD), Comprehensive Centers of Excellence and from grant P30-DK092924 from the NIDDK. NR 17 TC 16 Z9 16 U1 0 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2013 VL 62 IS 2 BP 261 EP 266 DI 10.1053/j.ajkd.2013.01.012 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 196OK UT WOS:000322784700012 PM 23473985 ER PT J AU Kumbhani, DJ Steg, PG Cannon, CP Eagle, KA Smith, SC Hoffman, E Goto, S Ohman, EM Bhatt, DL AF Kumbhani, Dharam J. Steg, Ph. Gabriel Cannon, Christopher P. Eagle, Kim A. Smith, Sidney C., Jr. Hoffman, Elaine Goto, Shinya Ohman, E. Magnus Bhatt, Deepak L. CA REduc Atherothrombosis Continued H TI Adherence to Secondary Prevention Medications and Four-year Outcomes in Outpatients with Atherosclerosis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Atherosclerosis; Cardiovascular disease; Compliance/adherence; Registry; Secondary prevention ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENT RATES; CORONARY-ARTERY-DISEASE; GUIDELINES; ATHEROTHROMBOSIS; CARE; MORTALITY; QUALITY; STROKE; HEART AB BACKGROUND: Although nonadherence with evidence-based secondary prevention medications is common in patients with established atherothrombotic disease, long-term outcomes studies are scant. We assessed the prevalence and long-term outcomes of nonadherence to secondary prevention (antiplatelet agents, statins, and antihypertensive agents) medications in stable outpatients with established atherothrombosis (coronary, cerebrovascular, or peripheral artery disease) enrolled in the international REduction of Atherothrombosis for Continued Health registry. METHODS: Adherence with these medications in eligible patients at baseline and 1-year follow-up was assessed. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke at 4 years. RESULTS: A total of 37,154 patients with established atherothrombotic disease were included. Adherence rates with all evidence-based medications at baseline and 1 year were 46.7% and 48.2%, respectively. Nonadherence with any medication at baseline (hazard ratio, 1.18; 95% confidence interval, 1.11-1.25) and at 1 year (hazard ratio, 1.19; 95% confidence interval, 1.11-1.28) were both significantly associated with an increased risk of the primary end point. The risk of all-cause mortality was similarly elevated. Corresponding numbers needed to treat were 31 and 25 patients for the composite end point and total mortality, respectively. This also was true for each disease-specific subgroup. Patients who were fully adherent at both time points had the lowest incidence of adverse outcomes, whereas patients who were nonadherent at both time points had the worst outcomes (P < .01). CONCLUSIONS: Our analysis of a large international registry demonstrates that nonadherence with evidence-based secondary prevention therapies in patients with established atherothrombosis is associated with a significant increase in long-term adverse events, including mortality. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kumbhani, Dharam J.] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Steg, Ph. Gabriel] INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Univ Paris Diderot, Paris, France. [Steg, Ph. Gabriel] AP HP, Paris, France. [Cannon, Christopher P.; Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cannon, Christopher P.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Cannon, Christopher P.; Hoffman, Elaine; Bhatt, Deepak L.] TIMI Study Grp, Boston, MA USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan) FX The REduction of Atherothrombosis for Continued Health (REACH) Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. The sponsors did not review this manuscript. The statistical analyses by the TIMI Study Group were funded with a grant from Sanofi-Aventis. NR 34 TC 34 Z9 35 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2013 VL 126 IS 8 BP 693 EP + DI 10.1016/j.amjmed.2013.01.033 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 197CS UT WOS:000322827200023 PM 23800583 ER PT J AU Booher, AM Isselbacher, EM Nienaber, CA Trimarchi, S Evangelista, A Montgomery, DG Froehlich, JB Ehrlich, MP Oh, JK Januzzi, JL O'Gara, P Sundt, TM Harris, KM Bossone, E Pyeritz, RE Eagle, KA AF Booher, Anna M. Isselbacher, Eric M. Nienaber, Christoph A. Trimarchi, Santi Evangelista, Arturo Montgomery, Daniel G. Froehlich, James B. Ehrlich, Marek P. Oh, Jae K. Januzzi, James L. O'Gara, Patrick Sundt, Thoralf M. Harris, Kevin M. Bossone, Eduardo Pyeritz, Reed E. Eagle, Kim A. CA IRAD Investigators TI The IRAD Classification System for Characterizing Survival after Aortic Dissection SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Aorta; Dissecting aneurysm; Survival analyses; Thoracic surgery ID LONG-TERM SURVIVAL; INTERNATIONAL REGISTRY; INSIGHTS; SURGERY; ANEURYSM; OUTCOMES AB BACKGROUND: The classification of aortic dissection into acute (<14 days from symptom onset) versus chronic (>= 14 days) is based on survival estimates of patients treated decades before modern diagnostic and treatment modalities were available. A new classification of aortic dissection in the current era may provide clinicians with a more precise method of characterizing the interaction of time, dissection location, and treatment type with survival. METHODS: We developed separate Kaplan-Meier survival curves for Type A and Type B aortic dissection using data from the International Registry of Aortic Dissection (IRAD). Daily survival was stratified based on type of therapy provided: medical therapy alone (medical), nonsurgical intervention plus medical therapy (endovascular), and open surgery plus medical therapy (surgical). The log-rank statistic was used to compare the survival curves of each management type within Type A and Type B aortic dissection. RESULTS: There were 1815 patients included, 67.3% male with mean age 62.0 +/- 14.2 years. When survival curves were constructed, 4 distinct time periods were noted: hyperacute (symptom onset to 24 hours), acute (2-7 days), subacute (8-30 days), and chronic (>30 days). Overall survival was progressively lower through the 4 time periods. CONCLUSIONS: This IRAD classification system can provide clinicians with a more robust method of characterizing survival after aortic dissection over time than previous methods. This system will be useful for treating patients, counseling patients and families, and studying new diagnostic and treatment methods. (C) 2013 Elsevier Inc. All rights reserved. C1 [Booher, Anna M.; Montgomery, Daniel G.; Froehlich, James B.; Eagle, Kim A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Isselbacher, Eric M.; Januzzi, James L.; Sundt, Thoralf M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Hosp Eppendorf Rostock, Dept Internal Med, Rostock, Germany. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. [Evangelista, Arturo] Hosp Gen Univ Vall dHebron, Dept Cardiol, Barcelona, Spain. [Ehrlich, Marek P.] Univ Vienna, Dept Cardiothorac Surg, A-1010 Vienna, Austria. [Oh, Jae K.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [O'Gara, Patrick] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Harris, Kevin M.] Minneapolis Heart Inst, Dept Cardiol, Minneapolis, MN USA. [Bossone, Eduardo] Dept Cardiol, Salerno, Italy. [Pyeritz, Reed E.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Booher, AM (reprint author), Univ Michigan, Cardiovasc Ctr, Cardiovasc Ctr 2344, SPC 5853,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM amanion@med.umich.edu RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU University of Michigan Health System; Varbedian Fund for Aortic Research; Hewlett Foundation; Mardigian Foundation; Gore Inc. FX IRAD is supported by grants from the University of Michigan Health System, the Varbedian Fund for Aortic Research, the Hewlett Foundation, the Mardigian Foundation, and Gore Inc. NR 14 TC 14 Z9 16 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2013 VL 126 IS 8 AR 730.e19 DI 10.1016/j.amjmed.2013.01.020 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 197CS UT WOS:000322827200029 PM 23885677 ER PT J AU Sobrin, L Seddon, JM AF Sobrin, Lucia Seddon, Johanna M. TI Regular Aspirin Use and Risk of Age-Related Macular Degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID LOW-DOSE ASPIRIN; EYE; METAANALYSIS; ASSOCIATION; MACULOPATHY; PREVENTION; DISEASE; TRIAL C1 [Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Seddon, Johanna M.] Tufts Univ, Ophthalm Epidemiol & Genet Serv, New England Eye Ctr, Tufts Med Ctr,Sch Med, Boston, MA 02111 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Seddon, JM (reprint author), Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv, Dept Ophthalmol, 800 Washington St 450, Boston, MA 02111 USA. EM jseddon@tuftsmalicalcenter.org NR 15 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2013 VL 156 IS 2 BP 213 EP 217 DI 10.1016/j.ajo.2013.04.023 PG 5 WC Ophthalmology SC Ophthalmology GA 196BK UT WOS:000322748200002 PM 23870358 ER PT J AU Roberts, DJ AF Roberts, Drucilla J. TI New Hope for Prevention of Preterm Delivery SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID CHRONIC CHORIOAMNIONITIS; CHRONIC INTERVILLOSITIS; INFLAMMATORY RESPONSE; UNKNOWN ETIOLOGY; CHRONIC VILLITIS; PREGNANT RATS; SEPTIC SHOCK; FETAL; BIRTH; EPIDEMIOLOGY C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Blossom St, Boston, MA 02114 USA. EM robertsd@helix.mgh.harvard.edu NR 40 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2013 VL 183 IS 2 BP 330 EP 332 DI 10.1016/j.ajpath.2013.06.001 PG 3 WC Pathology SC Pathology GA 194DR UT WOS:000322611700001 PM 23810739 ER PT J AU Paintlia, AS Paintlia, MK Mohan, S Singh, AK Singh, I AF Paintlia, Ajaib S. Paintlia, Manjeet K. Mohan, Sarumathi Singh, Avtar K. Singh, Inderjit TI AMP-Activated Protein Kinase Signaling Protects Oligodendrocytes that Restore Central Nervous System Functions in an Experimental Autoimmune Encephalomyelitis Model SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; MULTIPLE-SCLEROSIS; DEMYELINATING DISEASES; COMBINATION THERAPY; AXON DEGENERATION; OXIDATIVE STRESS; INTERFERON-GAMMA; PROGENITOR CELLS; NAD(P)H OXIDASE; ENERGY-BALANCE AB AMP-activated protein kinase (AMPK) signaling is reported to protect neurons under pathologic conditions; however, its effect on oligodendrocytes (OLs) remains to be elucidated. We investigated whether AMPK signaling protects OLs to restore central nervous system (CNS) functions in an experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Increased inflammation and demyelination in the CNS and peripheral immune responses were consistent with the observed clinical impairments in EAE animals, which were attenuated by treatment with metformin compared with vehicle. In addition, expressions of neurotrophic factors and of signatory genes of OL lineages were increased in the CNS of metformin-treated EAE animals. Likewise, metformin attenuated inflammatory response and enhanced expressions of neurotrophic factors, thereby protecting OLs via AMPK activation in mixed glial cultures stimulated with lipopolysaccharide/interferon gamma in vitro, as evidenced by analysis of the expression of signatory genes of 01(+)/MBP+ OLs and their cellular populations. Metformin also attenuated oxidative stress and malondialdehyde-containing protein levels, with corresponding induction of anti-oxidative defenses in OLs exposed to cytokines via AMPK activation. These effects of metformin were evident in the CNS of EAE animals. These data provide evidence that AMPK signaling is crucial to protect OLs and, thus, CNS functions in EAE animals. We conclude that AMPK activators, including metformin, have the potential to limit neurologic deficits in multiple sclerosis and related neurodegenerative disorders. C1 [Paintlia, Ajaib S.; Paintlia, Manjeet K.; Mohan, Sarumathi; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU NIH [VA-1BX001072, VA-BX001999, NS-22576, NS-37766, C06-RR018823] FX Supported by NIH grants VA-1BX001072, VA-BX001999, NS-22576, NS-37766, and C06-RR018823. NR 65 TC 13 Z9 15 U1 1 U2 10 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 AUG PY 2013 VL 183 IS 2 BP 526 EP 541 DI 10.1016/j.ajpath.2013.04.030 PG 16 WC Pathology SC Pathology GA 194DR UT WOS:000322611700021 PM 23759513 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 14 TC 0 Z9 0 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 2013 VL 305 IS 3 BP C239 EP C240 DI 10.1152/ajpcell.00135.2013 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 195LC UT WOS:000322702800001 PM 23677798 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora St Lukes Med Ctr, Aurora Res Fdn, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 0 Z9 0 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD AUG PY 2013 VL 305 IS 3 BP G205 EP G206 DI 10.1152/ajpgi.00154.2013 PG 2 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 195KP UT WOS:000322701400001 PM 23703653 ER PT J AU Yamamoto, S Nakase, H Matsuura, M Honzawa, Y Matsumura, K Uza, N Yamaguchi, Y Mizoguchi, E Chiba, T AF Yamamoto, Shuji Nakase, Hiroshi Matsuura, Minoru Honzawa, Yusuke Matsumura, Kayoko Uza, Norimitsu Yamaguchi, Yu Mizoguchi, Emiko Chiba, Tsutomu TI Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/beta-catenin signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE heparan sulfate; intestinal regeneration; Wnt signaling ID MOUSE SMALL INTESTINE; DOCKING-PROTEIN FRS2-ALPHA; STEM-CELLS; EXTRACELLULAR-MATRIX; MOLECULAR-MECHANISM; CRYSTAL-STRUCTURE; TUMOR-SUPPRESSOR; BARRIER FUNCTION; DIFFERENTIATION; DROSOPHILA AB Heparan sulfate (HS), a constituent of HS proteoglycans (HSPGs), is a linear polysaccharide present on the cell surface. HSPGs modulate functions of several growth factors and signaling molecules. We examined whether small intestinal epithelial HS plays some roles in crypt homeostasis using intestinal epithelium cell (IEC)-specific HS-deficient C57Bl/6 mice. Survival rate after total body irradiation was significantly reduced in HS-deficient mice due to profound intestinal injury. HS-deficient IECs exhibited Wnt/beta-catenin pathway disruption, decreased levels of beta-catenin nuclear localization, and reduced expression of Wnt target genes, including Lgr5 during crypt regeneration. Moreover, epithelial HS increased Wnt binding affinity of IECs, promoted phosphorylation of Wnt coreceptor LRP6, and enhanced Wnt/beta-catenin signaling following ex vivo stimulation with Wnt3a, whereas activation of canonical Wnt signaling following direct inhibition of glycogen synthase kinase-3 beta by lithium chloride was similar between HS-deficient and wild-type mice. Thus HS influences the binding affinity of IECs to Wnt, thereby promoting activation of canonical Wnt signaling and facilitating regeneration of small intestinal crypts after epithelial injury. C1 [Yamamoto, Shuji; Nakase, Hiroshi; Matsuura, Minoru; Honzawa, Yusuke; Matsumura, Kayoko; Uza, Norimitsu; Chiba, Tsutomu] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto 6068507, Japan. [Yamamoto, Shuji] Japan Soc Promot Sci, Tokyo, Japan. [Yamaguchi, Yu] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko] Harvard Univ, Sch Med, Boston, MA USA. RP Nakase, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. EM hiropy_n@kuhp.kyoto-u.ac.jp FU Ministry of Culture and Science of Japan [18590677]; Kato Memorial Trust for Nambyo Research; Japan Foundation for Applied Enzymology; Shimizu Foundation for the Promotion of Immunology Research; National Institutes of Health in the U.S. [ROI DK 80070]; Ministry of Education, Culture, Sports, Science, and Technology of Japan [16017240, 16017249, 17013051, 17659212, 18012029]; JSPS [15209024, 18209027]; Ministry of Health, Labor, and Welfare, Japan [nano005] FX This work was supported by a Grant-in-Aid for the Japan Society for the Promotion of Science Fellows (to S. Yamamoto); a Grant-in-Aid for Scientific Research (C) from the Ministry of Culture and Science of Japan (grant 18590677), the Kato Memorial Trust for Nambyo Research, the Japan Foundation for Applied Enzymology, the Shimizu Foundation for the Promotion of Immunology Research (to H. Nakase); a research grant (ROI DK 80070) from the National Institutes of Health in the U.S. (to E. Mizoguchi); Grants-in-Aid for Scientific Research (16017240, 16017249, 17013051, 17659212, and 18012029) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Grants-in-Aid for Scientific Research (15209024 and 18209027) from JSPS, and a Grant-in-Aid for Research on Measures for Intractable Disease, and Research on Advanced Medical Technology (nano005) from the Ministry of Health, Labor, and Welfare, Japan (to T. Chiba). NR 59 TC 6 Z9 6 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD AUG PY 2013 VL 305 IS 3 BP G241 EP G249 DI 10.1152/ajpgi.00480.2012 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 195KP UT WOS:000322701400005 PM 23744737 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 2013 VL 305 IS 3 BP H265 EP H266 DI 10.1152/ajpheart.00390.2013 PG 2 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 195KI UT WOS:000322700600001 PM 23686714 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Aurora Res Fdn, Med Coll Wisconsin, Dept Med, Milwaukee, WI USA. [Raff, Hershel] Aurora Res Fdn, Med Coll Wisconsin, Dept Surg, Milwaukee, WI USA. [Raff, Hershel] Aurora Res Fdn, Med Coll Wisconsin, Dept Physiol, Milwaukee, WI USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 14 TC 0 Z9 0 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 2013 VL 305 IS 3 BP R171 EP R172 DI 10.1152/ajpregu.00237.2013 PG 2 WC Physiology SC Physiology GA 195JO UT WOS:000322698400001 PM 23678023 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med Surg & Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 0 Z9 0 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2013 VL 305 IS 3 BP F227 EP F228 DI 10.1152/ajprenal.00269.2013 PG 2 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 195JU UT WOS:000322699000001 PM 23678044 ER PT J AU Criscitiello, C Azim, HA Agbor-tarh, D de Azambuja, E Piccart, M Baselga, J Eidtmann, H Di Cosimo, S Bradbury, I Rubio, IT AF Criscitiello, C. Azim, H. A., Jr. Agbor-tarh, D. de Azambuja, E. Piccart, M. Baselga, J. Eidtmann, H. Di Cosimo, S. Bradbury, I. Rubio, I. T. TI Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; neoadjuvant; HER2; surgery; breast conservation; trastuzumab ID ADJUVANT BREAST; PREOPERATIVE CHEMOTHERAPY; CONSERVING SURGERY; SYSTEMIC TREATMENT; RANDOMIZED-TRIAL; OPEN-LABEL; TRASTUZUMAB; COUNTRIES; CONSENSUS; METAANALYSIS AB The NeoALTTO trial showed that dual HER2 blockade nearly doubles the rate of pathologic complete response (pCR) in patients with primary HER2-positive breast cancer. However, this did not translate into a higher rate of breast-conserving surgery (BCS). In NeoALTTO, patients with HER2-positive breast cancer were randomly assigned to either trastuzumab, lapatinib or their combination with paclitaxel before surgery with pCR as the primary end point. We investigated the association between the surgery type and clinicopathological factors and response to treatment, adjusting for the treatment arm. Four hundred and twenty-nine patients were subjected to breast surgery. Two hundred and forty-two (56%) and 187 (44%) patients underwent mastectomy and BCS, respectively. In a logistic regression model, negative estrogen receptor (ER), multicentricity and the presence of a palpable mass before surgery were significantly associated with a low chance of BCS. Conversely, patients with small tumors and those eligible for BCS at diagnosis were managed more with BCS, independent of the treatment arm. Radiological response was not associated with the surgical decision. Tumor characteristics before neoadjuvant therapy play a main role in deciding the type of surgery calling for a clear consensus on the role of BCS in patients responding to neoadjuvant therapy. C1 [Criscitiello, C.] European Inst Oncol, Dept Med, Div Med Oncol, Milan, Italy. [Azim, H. A., Jr.; de Azambuja, E.; Piccart, M.] Univ Libre Brussels, Inst Jules Bordet, Dept Med, BrEAST Data Ctr, Brussels, Belgium. [Agbor-tarh, D.; Bradbury, I.] Frontier Sci, Kincraig, Kingussie, Scotland. [Baselga, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Eidtmann, H.] Univ Hosp Kiel, Kiel, Germany. [Di Cosimo, S.] Ist Nazl Tumori, Dept Med Oncol, I-20133 Milan, Italy. [Rubio, I. T.] Univ Vall DHebron, Breast Surg Oncol Unit, Barcelona, Spain. RP Azim, HA (reprint author), Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium. EM hatem.azim@bordet.be RI Serena, Di Cosimo/E-9418-2017 OI Serena, Di Cosimo/0000-0002-4666-8052 FU European Society for Medical Oncology FX CC acknowledges a TRANSBIG fellowship. HAA Jr acknowledges a fellowship grant from the European Society for Medical Oncology (no grant numbers). NR 29 TC 13 Z9 13 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2013 VL 24 IS 8 BP 1980 EP 1985 DI 10.1093/annonc/mdt129 PG 6 WC Oncology SC Oncology GA 190KR UT WOS:000322339300006 PM 23567146 ER PT J AU Weiner, M Skoog, L Fornander, T Nordenskjold, B Sgroi, DC Stal, O AF Weiner, M. Skoog, L. Fornander, T. Nordenskjold, B. Sgroi, D. C. Stal, O. TI Oestrogen receptor co-activator AIB1 is a marker of tamoxifen benefit in postmenopausal breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE AIB1; breast cancer; HER2; prognosis; SRC-3; treatment prediction ID TRANSCRIPTIONAL COACTIVATOR; PROTEIN EXPRESSION; RESISTANCE; COREGULATORS; ANTIESTROGEN; PREDICTS; GROWTH; SRC-3 AB The oestrogen receptor (ER) co-activator amplified in breast cancer 1 (AIB1) has been suggested as a treatment predictive and prognostic marker in breast cancer. Studies have however not been unanimous. AIB1 protein expression was analysed by immunohistochemistry on tissue micro-arrays with tumour samples from 910 postmenopausal women randomised to tamoxifen treatment or no adjuvant treatment. Associations between AIB1 expression, clinical outcome in the two arms and other clinicopathological variables were examined. In patients with ER-positive breast cancer expressing low tumour levels of AIB1 (< 75%), we found no significant difference in recurrence-free survival (RFS) or breast cancer-specific survival (BCS) between tamoxifen treated and untreated patients. In patients with high AIB1 expression (> 75%), there was a significant decrease in recurrence rate (HR 0.40, 95% CI 0.26-0.61, P < 0.001) and breast cancer mortality rate (HR 0.38, 95% CI 0.21-0.69, P = 0.0015) with tamoxifen treatment. In the untreated arm, we found high expression of AIB1 to be significantly associated with lower RFS (HR 1.74, 95% CI 1.20-2.53, P = 0.0038). Our results suggest that high AIB1 is a predictive marker of good response to tamoxifen treatment in postmenopausal women and a prognostic marker of decreased RFS in systemically untreated patients. C1 [Weiner, M.; Nordenskjold, B.; Stal, O.] Linkoping Univ, Fac Hlth Sci, Cty Council Ostergotland, Div Oncol,Dept Clin & Expt Med, Linkoping, Sweden. [Weiner, M.] Linkoping Univ, Dept Med & Hlth, Div Drug Res, Linkoping, Sweden. [Skoog, L.] Karolinska Inst, Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden. [Fornander, T.] Karolinska Inst, Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Sgroi, D. C.] Massachusetts Gen Hosp, Mol Pathol Res Unit, Dept Pathol, Boston, MA 02114 USA. RP Stal, O (reprint author), Linkoping Univ Hosp, Div Oncol, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden. EM olle.stal@liu.se FU Swedish Cancer Society [110504]; Swedish Research Council [B0771901] FX The work was supported by grants from the Swedish Cancer Society (#110504) and the Swedish Research Council (#B0771901). NR 24 TC 5 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2013 VL 24 IS 8 BP 1994 EP 1999 DI 10.1093/annonc/mdt159 PG 6 WC Oncology SC Oncology GA 190KR UT WOS:000322339300008 PM 23670096 ER PT J AU Henry, NL Xia, R Banerjee, M Gersch, C McConnell, D Giacherio, D Schott, AF Pearlman, M Stearns, V Partridge, AH Hayes, DF AF Henry, N. L. Xia, R. Banerjee, M. Gersch, C. McConnell, D. Giacherio, D. Schott, A. F. Pearlman, M. Stearns, V. Partridge, A. H. Hayes, D. F. TI Predictors of recovery of ovarian function during aromatase inhibitor therapy SO ANNALS OF ONCOLOGY LA English DT Article DE aromatase inhibitor; breast cancer; chemotherapy-induced ovarian failure; estradiol; ovarian function ID MASS-SPECTROMETRY ASSAY; EARLY BREAST-CANCER; CHEMOTHERAPY; TAMOXIFEN; ESTRADIOL; HORMONE; TRIALS; PLASMA AB Aromatase inhibitors (AIs) may cause a rise in estrogen levels due to ovarian function recovery in women with clinical chemotherapy-induced ovarian failure (CIOF). We carried out a prospective registry trial to identify predictors of ovarian function recovery during AI therapy. Women with hormone receptor (HR)-positive breast cancer who remained amenorrheic and had hormonal levels consistent with ovarian failure after adjuvant chemotherapy were enrolled in a multi-institutional clinical trial of anastrozole. Subjects underwent frequent assessment using an ultrasensitive estradiol assay. Multivariable analysis was used to evaluate clinical and biochemical predictors of ovarian function recovery within 48 weeks. Recovery of ovarian function during AI therapy was observed in 13 of 45 (28.9%) assessable subjects after a median 2.1 months (range 0.6-11.9). Median age at chemotherapy initiation was statistically significantly different between those who regained ovarian function (43 years, range 40-51) and those who remained postmenopausal (49 years, range 44-52; P < 0.0001). A significant proportion of women with CIOF recover ovarian function during AI therapy, including a woman over age 50 at initiation of chemotherapy. Tamoxifen remains the standard of care for women with CIOF. If an AI is used, patients should be monitored frequently with high-quality estradiol assays. Clinicaltrials.gov: NCT00555477. C1 [Henry, N. L.; Gersch, C.; Schott, A. F.; Hayes, D. F.] Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA. [Xia, R.; Banerjee, M.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [McConnell, D.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Giacherio, D.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Pearlman, M.] Univ Michigan, Sch Med, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Stearns, V.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Breast Canc Program, Baltimore, MD USA. [Partridge, A. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Henry, NL (reprint author), Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, 1500 East Med Ctr Dr,Med Inn Bldg C450, Ann Arbor, MI 48109 USA. EM norahh@med.umich.edu FU National Cancer Institute at the National Institutes of Health [5K07CA134747]; AstraZeneca; Fashion Footwear Association of New York/QVC Presents Shoes on Sale(TM); University of Michigan Comprehensive Cancer Center; Lilly Pharmaceuticals; sanofi aventis; Novartis; Pfizer FX This work was supported by the National Cancer Institute at the National Institutes of Health [grant number 5K07CA134747] to NLH; AstraZeneca; the Fashion Footwear Association of New York/QVC Presents Shoes on Sale (TM) to DFH and the University of Michigan Comprehensive Cancer Center to NLH. NLH received research funding from AstraZeneca, Lilly Pharmaceuticals and sanofi aventis. DFH received research funding from AstraZeneca. DFH and VS received research funding from Novartis and Pfizer. NR 12 TC 14 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2013 VL 24 IS 8 BP 2011 EP 2016 DI 10.1093/annonc/mdt149 PG 6 WC Oncology SC Oncology GA 190KR UT WOS:000322339300011 PM 23613476 ER PT J AU Choueiri, TK Je, Y Sonpavde, G Richards, CJ Galsky, MD Nguyen, PL Schutz, F Heng, DY Kaymakcalan, MD AF Choueiri, T. K. Je, Y. Sonpavde, G. Richards, C. J. Galsky, M. D. Nguyen, P. L. Schutz, F. Heng, D. Y. Kaymakcalan, M. D. TI Incidence and risk of treatment-related mortality in cancer patients treated with the mammalian target of rapamycin inhibitors SO ANNALS OF ONCOLOGY LA English DT Article DE cancer; renal cell carcinoma; mTOR inhibitors; fatal adverse events; meta-analysis ID RENAL-CELL CARCINOMA; ADVERSE DRUG-REACTIONS; PHASE-III; NEUROENDOCRINE TUMORS; INTERFERON-ALPHA; CLINICAL-TRIALS; EVEROLIMUS; TEMSIROLIMUS; THERAPY; EVENTS AB Inhibition of the mammalian target of rapamycin (mTOR) is an established treatment for multiple malignancies. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with mTOR inhibitors. PubMed, conferences and clinicaltrials.gov databases were searched for articles reported from January 1966 to June 2012. Eligible studies were limited to approved mTOR inhibitors (everolimus and temsirolimus) and reported on patients with cancer, randomized design and adequate safety profiles. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In all, 3193 patients from eight randomized, controlled trials (RCTs) were included, 2236 from everolimus trials and 957 from temsirolimus trials. The relative risk (RR) of FAEs related to mTOR inhibitors use was 2.20 (95% CI, 1.25-3.90; P = 0.006) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between everolimus and temsirolimus or between tumor types [renal cell carcinoma (RCC) versus non-RCC]. No evidence of publication bias was observed. The use of mTOR inhibitors is associated with a small but higher risk of FAEs compared to control patients. In the appropriate clinical scenario, the use of these drugs remains justified in their approved indications. C1 [Choueiri, T. K.; Nguyen, P. L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Je, Y.] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Sonpavde, G.] UAB, Ctr Comprehens Canc, Dept Med Oncol, Birmingham, AL USA. [Richards, C. J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Galsky, M. D.] Mt Sinai Sch Med, Tisch Canc Inst, Dept Med Oncol, New York, NY USA. [Nguyen, P. L.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Schutz, F.] Hosp Sao Paulo, Dept Med Oncol, Sao Paulo, Brazil. [Heng, D. Y.] Univ Calgary, Dept Med Oncol, Calgary, AB, Canada. [Kaymakcalan, M. D.] Dana Farber Canc Inst, Dept Pharm, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu FU Trust Family Research Fund for Kidney Cancer FX Trust Family Research Fund for Kidney Cancer. The funding source had no role in study design, analysis, interpretation or writing the manuscript. No grant number applicable. NR 32 TC 12 Z9 13 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2013 VL 24 IS 8 BP 2092 EP 2097 DI 10.1093/annonc/mdt155 PG 6 WC Oncology SC Oncology GA 190KR UT WOS:000322339300024 PM 23658373 ER PT J AU Shahian, DM He, X Jacobs, JP Rankin, JS Peterson, ED Welke, KF Filardo, G Shewan, CM O'Brien, SM AF Shahian, David M. He, Xia Jacobs, Jeffrey P. Rankin, J. Scott Peterson, Eric D. Welke, Karl F. Filardo, Giovanni Shewan, Cynthia M. O'Brien, Sean M. TI Issues in Quality Measurement: Target Population, Risk Adjustment, and Ratings SO ANNALS OF THORACIC SURGERY LA English DT Review ID PROFILING HOSPITAL PERFORMANCE; SURGERY REPORT CARDS; HEALTH-CARE; CLINICAL-OUTCOMES; MORTALITY-RATES; SURGICAL CARE; TASK-FORCE; DEATH RATE; DECISIONS; MODELS AB This review investigates three fundamental issues in health care performance measurement: selection of a homogeneous target population, risk adjustment, and assignment of quality rating categories. Many but not all organizations involved in quality measurement have adopted similar approaches to these important methodological issues. To illustrate the practical implications of different profiling strategies, we use The Society of Thoracic Surgeons' data to compare profiling results derived using prevailing analytical methodologies with those obtained from alternative approaches, exemplified by those of a well-known health care performance rating organization. We demonstrate the differences in provider classification that may result from these methodologic decisions. (C) 2013 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Clin Res Inst, Durham, NC USA. Congenital Heart Inst Florida, St Petersburg, FL USA. Vanderbilt Univ, Centennial Med Ctr, Nashville, TN 37235 USA. Seattle Childrens Hosp, Div Cardiothorac Surg, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. Soc Thorac Surg, Chicago, IL USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 44 TC 12 Z9 12 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2013 VL 96 IS 2 BP 718 EP 726 DI 10.1016/j.athoracsur.2013.03.029 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 201YA UT WOS:000323177800073 PM 23816415 ER PT J AU Gerrard, P Goldstein, R DiVita, MA Ryan, CM Mix, J Niewczyk, P Kazis, L Kowalske, K Zafonte, R Schneider, JC AF Gerrard, Paul Goldstein, Richard DiVita, Margaret A. Ryan, Colleen M. Mix, Jacqueline Niewczyk, Paulette Kazis, Lewis Kowalske, Karen Zafonte, Ross Schneider, Jeffrey C. TI Validity and Reliability of the FIM Instrument in the Inpatient Burn Rehabilitation Population SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Burns; Factor analysis; Outcome measures; Psychometrics; Rehabilitation; Validation ID FUNCTIONAL INDEPENDENCE MEASURE; ITEM RESPONSE THEORY; MOKKEN SCALE ANALYSIS; OUTCOMES; IRT; HEALTH AB Objective: To provide evidence of construct validity for the FIM instrument in the inpatient rehabilitation burn population. Design: Confirmatory factor analysis and item response theory were used to assess construct validity. Confirmatory factor analysis was performed on a 2-factor model of the FIM instrument and on a 6-subfactor model. Mokken scale analysis, a nonparametric item response theory, was performed on each of the FIM instrument's 2 major factors, motor and cognitive domains. Internal consistency using Cronbach alpha and Molenaar and Sijtsma's statistic was also examined. Setting: Inpatient rehabilitation facilities. Participants: Data from the Uniform Data System for Medical Rehabilitation for patients with an impairment code of burn injury from the years 2002 to 2011 were used for this analysis. A total of 7569 subjects were included in the study. Interventions: Not applicable. Main Outcome Measures: Comparative fit index results for the confirmatory factor analyses and adherence to assumptions of the Mokken scale model. Results: Confirmatory factor analysis provided a comparative fit index of 862 for the 2-factor model of 862 for the 6-subfactor model. Mokken scale analysis showed scalability coefficients of.681 and.891 for the motor and cognitive domains, respectively. Measures of internal consistency statistic gave values of >.95 for each major domain of the FIM instrument. Conclusions: The FIM instrument has evidence of validity and reliability as an outcome measure for patients with burn injuries in the inpatient rehabilitation setting. The 6-subfactor model provides a better fit than the 2-factor model by confirmatory factor analysis. There is evidence that the motor and cognitive domains each form valid unidimensional metrics based on nonparametric item response theory. Archives of Physical Medicine and Rehabilitation 2013;94:1521-26 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Gerrard, Paul; Goldstein, Richard; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [DiVita, Margaret A.; Mix, Jacqueline; Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY USA. [Ryan, Colleen M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv,Sumner Redstone Burn Ctr, Boston, MA 02115 USA. [Ryan, Colleen M.] Shriners Hosp Children, Boston, MA USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP Gerrard, P (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM pbgerrard@partners.org OI Gerrard, Paul/0000-0003-0654-5354; Kazis, Lewis/0000-0003-1800-5849; DiVita, Margaret/0000-0002-4878-2959 NR 30 TC 9 Z9 9 U1 1 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 AUG PY 2013 VL 94 IS 8 BP 1521 EP 1526 DI 10.1016/j.apmr.2013.02.019 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 196TZ UT WOS:000322801600012 PM 23473701 ER PT J AU Woodbury, ML Velozo, CA Richards, LG Duncan, PW AF Woodbury, Michelle L. Velozo, Craig A. Richards, Lorie G. Duncan, Pamela W. TI Rasch Analysis Staging Methodology to Classify Upper Extremity Movement Impairment After Stroke SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Rehabilitation; Stroke; Upper extremity ID FUGL-MEYER ASSESSMENT; COMPUTERIZED ADAPTIVE TEST; UPPER-LIMB; CLINICAL INTERPRETATION; OUTCOME MEASURES; MOTOR DEFICITS; HEMIPARESIS; REHABILITATION; RECOVERY; VALIDITY AB Objectives: To define Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) cutoff scores that demarcate 1 level of upper extremity (UE) impairment from another, and describe motor behaviors for each category in terms of expected FMA-UE item performance. Design: Analysis of existing FMA-UE data. Setting: University research laboratory. Participants: Persons (N=512) 0 to 145 days poststroke, 42 to 90 years of age. Intervention: Not applicable. Main Outcome Measures: An item response Rasch analysis staging method was used to calculate cutoff scores, which were defined as the RaschAndrich threshold values of 2 criterion FMA-UE items derived from an analysis of this sample. The analysis enabled conversion of cutoff scores, in logit units, to FMA-UE points assessed on 30 FMA-UE voluntary movement items (60 possible points). Results: The boundary between severe and moderate impairment was defined as -1.59 +/-.27 logits or 19 +/- 2 points; and between moderate and mild impairment was defined as 2.44 +/-.27 logits or 47 +/- 2 points. A description of expected performance in each impairment level shows that patients with severe impairment exhibited some distal movements, and patients with mild impairment had difficulties with some proximal movements. Conclusions: The cutoff scores, which link to a description of specific movements a patient can, can partially, and cannot perform, may enable formation of heterogeneous patient groups, advance efforts to identify specific movement therapy targets, and define treatment response in terms of specific movement that changed or did not change with therapy. Archives of Physical Medicine and Rehabilitation 2013;94:1527-33 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Woodbury, Michelle L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Woodbury, Michelle L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Velozo, Craig A.] Malcom Randall VA Med Ctr, Gainesville, FL USA. [Velozo, Craig A.] Univ Florida, Dept Occupat Therapy, Gainesville, FL USA. [Richards, Lorie G.] Univ Utah, Dept Occupat Therapy, Salt Lake City, UT USA. [Duncan, Pamela W.] Wake Forest Baptist Hlth, Dept Neurol, Winston Salem, NC USA. RP Woodbury, ML (reprint author), Med Univ S Carolina, Coll Hlth Profess, 77 President St, Charleston, SC 29425 USA. EM WoodbuML@musc.edu FU Ralph H. Johnson Veterans Affairs Medical Center; Office of Research and Development, Rehabilitation Research and Development, Department of Veterans Affairs, Career Development-2 Award [B-6332W]; National Institute on Aging, Claude D. Pepper Center [5P60AG14635] FX Supported by the Ralph H. Johnson Veterans Affairs Medical Center and the Office of Research and Development, Rehabilitation Research and Development, Department of Veterans Affairs, Career Development-2 Award (grant no. B-6332W); and the National Institute on Aging, Claude D. Pepper Center (grant no. 5P60AG14635). NR 51 TC 13 Z9 13 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2013 VL 94 IS 8 BP 1527 EP 1533 DI 10.1016/j.apmr.2013.03.007 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 196TZ UT WOS:000322801600013 PM 23529144 ER PT J AU Cameron, MH Asano, M Bourdette, D Finlayson, ML AF Cameron, Michelle H. Asano, Miho Bourdette, Dennis Finlayson, Marcia L. TI People With Multiple Sclerosis Use Many Fall Prevention Strategies but Still Fall Frequently SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Accidental falls; Activities of daily living; Multiple sclerosis; Rehabilitation; Self care ID OLDER-PEOPLE; RISK-FACTORS; ADULTS; METAANALYSIS; COMMUNITY; PROGRAM; BALANCE; TRIAL; DRUGS; WOMEN AB Objective: To compare the use of fall prevention strategies by people with multiple sclerosis (MS) who do or do not fall. Design: Prospective cohort. All assessments were completed between January 2011 and December 2011. Data used in this analysis were collected as part of an observational study that included baseline assessment followed by prospective counting of falls using fall calendars. Setting: Veterans Affairs and university medical centers. Participants: People with MS (N=58) of any subtype, aged 18 to 50 years, with Expanded Disability Status Scale score <6.0, recruited from MS clinics at the Portland VA Medical Center and Oregon Health and Science University and from the surrounding areas. Interventions: Not applicable. Main Outcome Measures: Measures included the occurrence of falls over 3 months and scores on the Fall Prevention Strategy Survey (FPSS) and the relations between fall prevention strategy use reported on the FPSS and falls. Results: A total of 52 subjects completed the study. Of these, 33 (63%) subjects fell at least once in the 3-month period, and 19 (36%) subjects did not fall. The mean total FPSS score for the fallers was significantly higher than the nonfallers (mean +/- SD, 8.1 +/- 6.4 vs 4.0 +/- 4.1; range, 0-20 vs 0-15; P=.007), and FPSS scores correlated with monthly fall rates (rho=.49, P=.01). A higher proportion of fallers than nonfallers used the strategies of turning on lights at home, asking others for help, and talking to a health care professional about fall prevention. However, both groups rarely talked to a health care professional about fall prevention or asked a provider to check whether any medications might increase fall risk. Conclusions: People with MS who fall use more fall prevention strategies than those who do not fall. Archives of Physical Medicine and Rehabilitation 2013;94:1562-6 (C) 2013 by the American Congress of Rehabilitation Medicine C1 [Cameron, Michelle H.; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Cameron, Michelle H.; Bourdette, Dennis] Portland VA Med Ctr, Portland, OR USA. [Asano, Miho; Finlayson, Marcia L.] Queens Univ, Sch Rehabil Therapy, Kingston, ON, Canada. RP Cameron, MH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, L226,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM cameromi@ohsu.edu RI Finlayson, Marcia /G-2654-2014 OI Finlayson, Marcia /0000-0002-1774-4810 FU Department of Veterans Affairs, Rehabilitation Research and Development [E7244W] FX Supported by the Department of Veterans Affairs, Rehabilitation Research and Development (grant no. E7244W). NR 26 TC 3 Z9 4 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2013 VL 94 IS 8 BP 1562 EP 1566 DI 10.1016/j.apmr.2013.01.021 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 196TZ UT WOS:000322801600018 PM 23391522 ER PT J AU Urraca, N Cleary, J Brewer, V Pivnick, EK McVicar, K Thibert, RL Schanen, NC Esmer, C Lamport, D Reiter, LT AF Urraca, Nora Cleary, Julie Brewer, Victoria Pivnick, Eniko K. McVicar, Kathryn Thibert, Ronald L. Schanen, N. Carolyn Esmer, Carmen Lamport, Dustin Reiter, Lawrence T. TI The Interstitial Duplication 15q11.2-q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature SO AUTISM RESEARCH LA English DT Article DE autism; 15q duplication; imprinting; copy number variation; UBE3A ID DE-NOVO MUTATIONS; PERVASIVE DEVELOPMENTAL DISORDERS; SLEEP HABITS QUESTIONNAIRE; PRADER-WILLI-SYNDROME; SPECTRUM DISORDERS; ANGELMAN-SYNDROME; PROXIMAL 15Q; LINKAGE-DISEQUILIBRIUM; RECEPTOR SUBTYPES; REGION AB Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. (C) 2013 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Urraca, Nora; Reiter, Lawrence T.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. [Brewer, Victoria; Pivnick, Eniko K.; McVicar, Kathryn; Reiter, Lawrence T.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Cleary, Julie] Univ Memphis, Dept Speech & Language Pathol, Memphis, TN 38152 USA. [Thibert, Ronald L.] Mass Gen Hosp, Dept Neurol, Boston, MA USA. [Schanen, N. Carolyn] Nemours Biomed Res, Human Genet Res Lab, Wilmington, DE USA. [Esmer, Carmen] Hosp Cent Dr Ignacio Morones Prieto, Dept Genet, San Luis Potosi, Mexico. [Lamport, Dustin] Univ S Alabama, Dept Psychol, Mobile, AL 36688 USA. [Pivnick, Eniko K.] Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA. RP Reiter, LT (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Neurol, 855 Monroe Ave,Link 415, Memphis, TN 38163 USA. EM lreiter@uthsc.edu OI Reiter, Lawrence/0000-0002-4100-2630 FU Herbert and Mary Shainberg Neuroscience Fund; Le Bonheur Children's Foundation FX This work was funded by a grant from the Herbert and Mary Shainberg Neuroscience Fund to L.T.R. and additional support from the Le Bonheur Children's Foundation to N.U. The authors would like to thank Edwin Cook for his insightful critical review of the manuscript as well as the Dup15q Alliance and all of the families who participated in this study. NR 57 TC 40 Z9 42 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD AUG PY 2013 VL 6 IS 4 BP 268 EP 279 DI 10.1002/aur.1284 PG 12 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 200ZY UT WOS:000323111700005 PM 23495136 ER PT J AU Pompili, M Gonda, X Serafini, G Innamorati, M Sher, L Amore, M Rihmer, Z Girardi, P AF Pompili, Maurizio Gonda, Xenia Serafini, Gianluca Innamorati, Marco Sher, Leo Amore, Mario Rihmer, Zoltan Girardi, Paolo TI Epidemiology of suicide in bipolar disorders: a systematic review of the literature SO BIPOLAR DISORDERS LA English DT Review DE adults; bipolar disorder; completed suicides; risk factors; suicide rates ID MAJOR DEPRESSION; RISK-FACTORS; FOLLOW-UP; COMPLETED SUICIDE; ANXIETY DISORDERS; MIXED-STATE; STEP-BD; LITHIUM; BEHAVIOR; PREVALENCE AB Objective: Suicidal behavior is a major public health problem worldwide, and its prediction and prevention represent a challenge for everyone, including clinicians. The aim of the present paper is to provide a systematic review of the existing literature on the epidemiology of completed suicides in adult patients with bipolar disorder (BD). Methods: We performed a Pubmed/Medline, Scopus, PsycLit, PsycInfo, and Cochrane database search to identify all relevant papers published between 1980 and 2011. A total of 34 articles meeting our inclusion criteria were included in the present review. Results: Several prospective follow-up contributions, many retrospective analyses, and a few psychological autopsy studies and review articles investigated the epidemiology of completed suicides in patients with BD. The main finding of the present review was that the risk for suicide among BD patients was up to 20-30 times greater than that for the general population. Conclusion: Special attention should be given to the characteristics of suicides in patients with BD. Better insight and understanding of suicide and suicidal risk in this very disabling illness should ultimately help clinicians to adequately detect, and thus prevent, suicidal acts in patients with BD. C1 [Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Girardi, Paolo] Univ Roma La Sapienza, St Andrea Hosp, Dept Neurosci Mental Hlth & Sensory Organs, Suicide Prevent Ctr, I-00189 Rome, Italy. [Gonda, Xenia; Rihmer, Zoltan] Semmelweis Univ, Dept Clin & Theoret Mental Hlth, Kutvolgyi Clin Ctr, H-1085 Budapest, Hungary. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Amore, Mario] Univ Genoa, Sect Psychiat, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy. [Girardi, Paolo] Villa Rosa Med Res Ctr, Viterbo, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, St Andrea Hosp, Dept Psychiat, 1035-1039 Via Grottarossa, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it OI Innamorati, Marco/0000-0003-1389-2290; Pompili, Maurizio/0000-0003-1886-4977 NR 73 TC 56 Z9 57 U1 11 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2013 VL 15 IS 5 SI SI BP 457 EP 490 DI 10.1111/bdi.12087 PG 34 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 196KV UT WOS:000322774700002 PM 23755739 ER PT J AU Yerevanian, BI Choi, YM AF Yerevanian, Boghos I. Choi, Young Mee TI Impact of psychotropic drugs on suicide and suicidal behaviors SO BIPOLAR DISORDERS LA English DT Review DE anticonvulsants; antidepressants; antipsychotics; bipolar disorder; lithium; mood disorder; psychotropic drugs; sedatives and hypnotics; suicide ID BIPOLAR-I DISORDER; PLACEBO-CONTROLLED TRIAL; LITHIUM MAINTENANCE TREATMENT; TREATMENT ENHANCEMENT PROGRAM; TERM ANTIDEPRESSANT TREATMENT; MAJOR AFFECTIVE-DISORDERS; CONTROLLED 18-MONTH TRIAL; STEP-BD; DOUBLE-BLIND; ANTIEPILEPTIC DRUGS AB Objective: To examine the impact of psychotropic drugs on suicide and suicidal behaviors in bipolar disorders. Methods: A Medline search of articles published from January 1960 to January 2013 was performed using relevant keywords to identify studies examining the relationship of psychotropic drugs to suicidal behaviors. The publications were further reviewed for relevant references and information. Additionally, the US Food and Drug Administration Center for Drug Evaluation Research website was searched. Results: The available studies used differing methodologies, making interpretation of the findings difficult. Studies suggest that antidepressants may increase suicidal risk in bipolar disorder, this possibly being related to the induction of broadly defined mixed states. There is no evidence that antiepileptic drugs as a class increase suicidal risk in patients with bipolar disorder. Only lithium provides convincing data that it reduces the risk of suicide over the long term. There is little known regarding the effects of antipsychotics, as well as anti-anxiety and hypnotic drugs, on suicidal behavior. Conclusions: The available evidence for the impact of psychotropics on suicidal risk in patients with bipolar disorder is largely methodologically flawed and, except for a few instances, clinically not useful at this point. Adequately powered, prospective randomized controlled studies are needed to assess the impact of each class of psychotropic and each psychotropic as well as common combination therapies. Until such studies have been carried out, clinicians are urged to exercise caution in using these drugs and rely on the traditional means of carefully assessing and monitoring patients with bipolar disorder who are at high risk for suicide. C1 [Yerevanian, Boghos I.; Choi, Young Mee] Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Sepulveda Ambulatory Care Ctr, North Hills, CA 91343 USA. [Yerevanian, Boghos I.; Choi, Young Mee] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Yerevanian, BI (reprint author), Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Sepulveda Ambulatory Care Ctr, 16111 Plummer St Bldg 10,MC 116A3, North Hills, CA 91343 USA. EM byerevan@ucla.edu NR 137 TC 18 Z9 20 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2013 VL 15 IS 5 SI SI BP 594 EP 621 DI 10.1111/bdi.12098 PG 28 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 196KV UT WOS:000322774700011 PM 23869907 ER PT J AU Loren, AW Brazauskas, R Chow, EJ Gilleece, M Halter, J Jacobsohn, DA Joshi, S Pidala, J Quinn, GP Wang, Z Apperley, JF Burns, LJ Hale, GA Hayes-Lattin, BM Kamble, R Lazarus, H McCarthy, PL Reddy, V Warwick, AB Bolwell, BJ Duncan, C Socie, G Sorror, ML Wingard, JR Majhail, NS AF Loren, A. W. Brazauskas, R. Chow, E. J. Gilleece, M. Halter, J. Jacobsohn, D. A. Joshi, S. Pidala, J. Quinn, G. P. Wang, Z. Apperley, J. F. Burns, L. J. Hale, G. A. Hayes-Lattin, B. M. Kamble, R. Lazarus, H. McCarthy, P. L. Reddy, V. Warwick, A. B. Bolwell, B. J. Duncan, C. Socie, G. Sorror, M. L. Wingard, J. R. Majhail, N. S. TI Physician perceptions and practice patterns regarding fertility preservation in hematopoietic cell transplant recipients SO BONE MARROW TRANSPLANTATION LA English DT Article DE hematopoietic cell transplantation; autologous; allogeneic; fertility preservation; infertility; pregnancy ID BONE-MARROW-TRANSPLANTATION; PREGNANCY OUTCOMES; CANCER-PATIENTS; RESPONSE RATES; ONCOLOGISTS; INFERTILITY; CHILDHOOD; SURVIVORS; IMPACT; RISK AB Physician practice variation may be a barrier to informing hematopoietic cell transplant (HCT) recipients about fertility preservation (FP) options. We surveyed HCT physicians in the United States to evaluate FP knowledge, practices, perceptions and barriers. Of the 1035 physicians invited, 185 completed a 29-item web-survey. Most respondents demonstrated knowledge of FP issues and discussed and felt comfortable discussing FP. However, only 55% referred patients to an infertility specialist. Most did not provide educational materials to patients and only 35% felt that available materials were relevant for HCT. Notable barriers to discussing FP included perception that patients were too ill to delay transplant (63%), patients were already infertile from prior therapy (92%) and time constraints (41%). Pediatric HCT physicians and physicians with access to an infertility specialist were more likely to discuss FP and to discuss FP even when prognosis was poor. On analyses that considered physician demographics, knowledge and perceptions as predictors of referral for FP, access to an infertility specialist and belief that patients were interested in FP were observed to be significant. We highlight variation in HCT physician perceptions and practices regarding FP. Physicians are generally interested in discussing fertility issues with their patients but lack educational materials. C1 [Loren, A. W.] Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Brazauskas, R.; Wang, Z.] Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA. [Chow, E. J.; Sorror, M. L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Gilleece, M.] St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. [Halter, J.] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Jacobsohn, D. A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Joshi, S.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Quinn, G. P.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Apperley, J. F.] Univ London Imperial Coll Sci Technol & Med, London, England. [Burns, L. J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Hale, G. A.] Childrens Hosp, St Petersburg, FL USA. [Hayes-Lattin, B. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kamble, R.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Lazarus, H.] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [McCarthy, P. L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Reddy, V.] Univ Cent Florida, Orlando, FL 32816 USA. [Warwick, A. B.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Bolwell, B. J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Duncan, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Socie, G.] Hop St Louis, Paris, France. [Wingard, J. R.] Shands HealthCare & Univ Florida, Gainesville, FL USA. [Majhail, N. S.] Natl Marrow Donor Program, Minneapolis, MN USA. RP Majhail, NS (reprint author), Natl Marrow Donor Program, Ctr Int Blood & Marrow Transplant Res, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA. EM nmajhail@nmdp.org FU Public Health Service from the National Cancer Institute, the National Heart, Lung and Blood Institute [U24-CA76518]; National Institute of Allergy and Infectious Diseases; 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; 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; Leukemia and Lymphoma Society; 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.; Wellpoint, Inc. FX The Center for International Blood and Marrow Transplant Research is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, the National Heart, Lung and Blood Institute and the National Institute of Allergy and Infectious Diseases; a Grant/Cooperative Agreement 5U01HL069294 from 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 and 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. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 19 TC 23 Z9 23 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2013 VL 48 IS 8 BP 1091 EP 1097 DI 10.1038/bmt.2013.13 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 197AR UT WOS:000322819900013 PM 23419436 ER PT J AU Treister, N Chai, X Kurland, B Pavletic, S Weisdorf, D Pidala, J Palmer, J Martin, P Inamoto, Y Arora, M Flowers, M Jacobsohn, D Jagasia, M Arai, S Lee, SJ Cutler, C AF Treister, N. Chai, X. Kurland, B. Pavletic, S. Weisdorf, D. Pidala, J. Palmer, J. Martin, P. Inamoto, Y. Arora, M. Flowers, M. Jacobsohn, D. Jagasia, M. Arai, S. Lee, S. J. Cutler, C. TI Measurement of oral chronic GVHD: results from the Chronic GVHD Consortium SO BONE MARROW TRANSPLANTATION LA English DT Article DE oral cavity; SCT; GVHD; quality of life ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CLINICAL-TRIALS; THERAPEUTIC RESPONSE; CRITERIA; RELIABILITY; DESIGN AB Oral chronic GVHD (cGVHD) is a serious complication of alloSCT. Scales and instruments to measure oral cGVHD activity and severity have not been prospectively validated. The objective of this study was to describe the characteristics of oral cGVHD and determine the measures most sensitive to change. Patients enrolled in the cGVHD Consortium with oral involvement were included. Clinicians scored oral changes according to the National Institutes of Health (NIH) criteria, and patients completed symptom and quality-of-life measures at each visit. Both rated change on an eight-point scale. Of the 458 participants, 72% (n = 331) had objective oral involvement at enrollment. Lichenoid change was the most common feature (n = 293; 89%). At visits where oral change could be assessed, 50% of clinicians and 56% of patients reported improvement, with worsening reported in 4-5% for both the groups (weighted kappa = 0.41). Multivariable regression modeling suggested that the measurement changes most predictive of perceived change by clinicians and patients were erythema and lichenoid, NIH severity and symptom scores. Oral cGVHD is common and associated with a range of signs and symptoms. Measurement of erythema and lichenoid changes and symptoms may adequately capture the activity of oral cGVHD in clinical trials but require prospective validation. C1 [Treister, N.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Chai, X.; Kurland, B.; Martin, P.; Inamoto, Y.; Flowers, M.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Pavletic, S.] NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Weisdorf, D.; Arora, M.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Pidala, J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA. [Palmer, J.] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA. [Jacobsohn, D.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA. [Jagasia, M.] Vanderbilt Ingram Canc Ctr, Div Hematol Stem Cell Transplantat, Nashville, TN USA. [Arai, S.] Stanford Univ, Ctr Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Cutler, C.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Treister, N (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,3rd Floor, Boston, MA 02115 USA. EM ntreister@partners.org OI Kurland, Brenda/0000-0002-5669-0595 FU [CA118953]; [CA163438] FX This work was supported by Grants CA118953 and CA163438. NR 27 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2013 VL 48 IS 8 BP 1123 EP 1128 DI 10.1038/bmt.2012.285 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 197AR UT WOS:000322819900018 PM 23353804 ER PT J AU Bullock-Rest, N Cerny, A Sweeney, C Palumbo, C Kurowski, K Blumstein, SE AF Bullock-Rest, Natasha Cerny, Alissa Sweeney, Carol Palumbo, Carole Kurowski, Kathleen Blumstein, Sheila E. TI Neural systems underlying the influence of sound shape properties of the lexicon on spoken word production: Do fMRI findings predict effects of lesions in aphasia? SO BRAIN AND LANGUAGE LA English DT Article DE Aphasia; Spoken word production; Lesions; Functional neuroimaging; Voice-onset time ID VOICE ONSET TIME; PHONOLOGICAL NEIGHBORHOOD DENSITY; EVENT-RELATED FMRI; SPEECH PRODUCTION; PHONOTACTIC PROBABILITY; WERNICKES APHASIA; PREFRONTAL CORTEX; ELDERLY ADULTS; COMPETITION; RETRIEVAL AB Previous behavioral work has shown that the phonetic realization of words in spoken word production is influenced by sound shape properties of the lexicon. A recent fMRI study (Peramunage, Blumstein, Myers, Goldrick, & Baese-Berk, 2011) showed that this influence of lexical structure on phonetic implementation recruited a network of areas that included the supramarginal gyrus (SMG) extending into the posterior superior temporal gyrus (pSTG) and the inferior frontal gyrus (IFG). The current study examined whether lesions in these areas result in a concomitant functional deficit. Ten individuals with aphasia and 8 normal controls read words aloud in which half had a voiced stop consonant minimal pair (e.g. tame; dame), and the other half did not (e.g. tooth; *dooth). Voice onset time (VOT) analysis of the initial voiceless stop consonant revealed that aphasic participants with lesions including the IFG and/or the SMG behaved as did normals, showing VOT lengthening effects for minimal pair words compared to non-minimal pair words. The failure to show a functional deficit in the production of VOT as a function of the lexical properties of a word with damage in the IFG or SMG suggests that fMRI findings do not always predict effects of lesions on behavioral deficits in aphasia. Nonetheless, the pattern of production errors made by the aphasic participants did reflect properties of the lexicon, supporting the view that the SMG and IFG are part of a lexical network involved in spoken word production. (c) 2013 Elsevier Inc. All rights reserved. C1 [Bullock-Rest, Natasha; Cerny, Alissa; Sweeney, Carol; Kurowski, Kathleen; Blumstein, Sheila E.] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. [Palumbo, Carole; Blumstein, Sheila E.] Boston Univ, Sch Med, Harold Goodglass Aphasia Res Ctr, Boston, MA 02215 USA. [Bullock-Rest, Natasha; Sweeney, Carol; Palumbo, Carole; Kurowski, Kathleen; Blumstein, Sheila E.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Blumstein, Sheila E.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. RP Blumstein, SE (reprint author), Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. EM Sheila_Blumstein@Brown.EDU FU NIH [DC00314, DC05207] FX Portions of this research were presented at the 49th Annual Meeting of the Academy of Aphasia, Montreal, Quebec, Canada, October 16-18, 2011. This research was supported in part by NIH grants DC00314 to Brown University and DC05207 to the Boston University School of Medicine. This material is the result of work supported with resources and the use of facilities at the Department of Veterans Affairs Medical Centers in Boston, MA and Providence, RI. The content is solely the responsibility of the authors and does not necessarily represent the official views or policy of the Department of Veterans Affairs, the National Institute on Deafness and Other Communication Disorders, or the National Institutes of Health. We thank John Mertus for his technical contributions to this project. NR 65 TC 1 Z9 1 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 0093-934X J9 BRAIN LANG JI Brain Lang. PD AUG PY 2013 VL 126 IS 2 BP 159 EP 168 DI 10.1016/j.bandl.2013.05.002 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 197KL UT WOS:000322850000006 PM 23743183 ER PT J AU Jevtovic-Todorovic, V Absalom, AR Blomgren, K Brambrink, A Crosby, G Culley, DJ Fiskum, G Giffard, RG Herold, KF Loepke, AW Ma, D Orser, BA Planel, E Slikker, W Soriano, SG Stratmann, G Vutskits, L Xie, Z Hemmings, HC AF Jevtovic-Todorovic, V. Absalom, A. R. Blomgren, K. Brambrink, A. Crosby, G. Culley, D. J. Fiskum, G. Giffard, R. G. Herold, K. F. Loepke, A. W. Ma, D. Orser, B. A. Planel, E. Slikker, W., Jr. Soriano, S. G. Stratmann, G. Vutskits, L. Xie, Z. Hemmings, H. C., Jr. TI Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthesia; general; anaesthetics; cognitive disorder; neurotoxicity syndromes; postoperative complications ID POSTOPERATIVE COGNITIVE DYSFUNCTION; DEVELOPING RAT-BRAIN; KETAMINE-INDUCED NEUROAPOPTOSIS; MEDIAL PREFRONTAL CORTEX; NITROUS-OXIDE ANESTHESIA; ARTERY-BYPASS-SURGERY; D-ASPARTATE RECEPTOR; NEURONAL CELL-DEATH; NEURAL STEM-CELLS; ALZHEIMERS-DISEASE AB Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches. C1 [Jevtovic-Todorovic, V.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA 22903 USA. [Absalom, A. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Anesthesiol, Groningen, Netherlands. [Blomgren, K.] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Brambrink, A.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Crosby, G.; Culley, D. J.] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Crosby, G.; Culley, D. J.; Soriano, S. G.] Harvard Univ, Sch Med, Boston, MA USA. [Fiskum, G.] Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. [Giffard, R. G.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Herold, K. F.; Hemmings, H. C., Jr.] Weill Cornell Med Coll, Dept Anesthesiol, New York, NY USA. [Loepke, A. W.] Cincinnati Childrens Hosp Med Ctr, Dept Anesthesia, Cincinnati, OH USA. [Loepke, A. W.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Loepke, A. W.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Ma, D.] Univ London Imperial Coll Sci Technol & Med, Sect Anaesthet Pain Med & Intens Care, Dept Surg & Canc, London, England. [Orser, B. A.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Anesthesia, Toronto, ON, Canada. [Planel, E.] Univ Laval, Dept Psychiat & Neurosci, Quebec City, PQ, Canada. [Slikker, W., Jr.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Soriano, S. G.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Stratmann, G.] UCSF, Dept Anesthesia & Crit Care, San Francisco, CA USA. [Stratmann, G.] Grp Anesthesia Serv, Los Gatos, CA USA. [Vutskits, L.] Univ Hosp Geneva, Dept Anesthesiol Pharmacol & Intens Care, Geneva, Switzerland. [Xie, Z.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA. [Xie, Z.] Harvard Univ, Sch Med, Charlestown, MA USA. [Hemmings, H. C., Jr.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA. RP Jevtovic-Todorovic, V (reprint author), Univ Virginia, Dept Anesthesiol, Charlottesville, VA 22903 USA. EM vj3w@hscmail.mcc.virginia.edu; hchemmi@med.cornell.edu OI Absalom, Anthony/0000-0001-7563-9157; Blomgren, Klas/0000-0002-0476-7271 FU National Institute of Academic Anaesthesia; Dutch Association of Anesthesiologists; Swedish Research Council; Swedish Childhood Cancer Foundation; Swedish Cancer Foundation; StratNeuro Network at the Karolinska Institute; Stockholm and Gothenburg Freemasons' Pediatric Research; National Institutes of Health (Bethesda, MD, USA) [K08 GM077057, R01 GM088817, 2P01 1HD16596-26, GM49831, NS053898, GM58055, NS56315]; US Air Force [FA8650-11-2-6D04]; US Army [W81XWH-13-1-0016, W81XWH-09-2-0187] FX A.R.A., National Institute of Academic Anaesthesia and Dutch Association of Anesthesiologists; K.B., Swedish Research Council, the Swedish Childhood Cancer Foundation, the Swedish Cancer Foundation, governmental grants from Agreement Concerning Research and Education of Doctors (ALF), the StratNeuro Network at the Karolinska Institute, the Stockholm and Gothenburg Freemasons' Pediatric Research grants; D.C., William F. Milton Fund, National Institutes of Health (Bethesda, MD, USA) K08 GM077057; G.C., National Institutes of Health R01 GM088817; G. F., National Institutes of Health 2P01 1HD16596-26, US Air Force FA8650-11-2-6D04, US Army W81XWH-13-1-0016 and W81XWH-09-2-0187; R.G.G., National Institutes of Health GM49831 and NS053898; H.C.H., National Institutes of Health GM58055 and NS56315; KFH HE4554/5-1 DFG (German Research Foundation); V.J.-T., NIH/NICHD HD 44517 and American Recovery and Reinvestment Act supplement HD 44517S, John E. Fogarty Award TW007423-128322, March of Dimes National Award and Harold Carron endowment. V.J.-T. was an Established Investigator of the American Heart Association; D.M., Medical Research Council, Alzheimer's Society-Bupa Foundation, BJA/RCoA, AAGBI, Westminster Medical School Research Trust, Action Medical Research and SPARKS, UK and European Society of Anesthesiology, Brussels; B.A.O., Canada Research Chair in Anesthesia, and Canadian Institutes of Health Research; E. P., Canadian Institutes for Health Research (MOP-106423, PCN-102993), Natural Sciences and Engineering Research Council (354722), Canada Foundation for Innovation (23905), and Research Scholar Career Awards (16205, 20048) from the Fonds de la Recherche en Sante du Quebec; S.G.S., Boston Children's Hospital Endowed Chair in Pediatric Neuroanesthesia; G.S., John Severinghaus Research Award Department of Anesthesia and Perioperative Care, UCSF; L.V., Swiss National Science Foundation; Z.X., National Institutes of Health R21AG038994, R01 GM088801, and R01 AG041274, Investigator-initiated research grant from Alzheimer's Association, Chicago, IL, USA, and Cure Alzheimer's Fund, Wellesley, MA, USA. NR 83 TC 74 Z9 80 U1 5 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD AUG PY 2013 VL 111 IS 2 BP 143 EP 151 DI 10.1093/bja/aet177 PG 9 WC Anesthesiology SC Anesthesiology GA 190KF UT WOS:000322337900005 PM 23722106 ER PT J AU Evans, KC Keil, B McLaren, DG Bianciardi, M Song, TY Triantafyllou, C AF Evans, K. C. Keil, B. McLaren, D. G. Bianciardi, M. Song, T. -Y. Triantafyllou, C. TI Hypercapnia evokes amygdalo-thalamic and brainstem activity: a 7 T functional magnetic resonance imaging study in healthy humans SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract CT Spring Meeting of the Anaesthetic-Research-Society CY APR 11-12, 2013 CL Merton Coll, Oxford, ENGLAND SP Anaesthet Res Soc HO Merton Coll C1 [Evans, K. C.; Song, T. -Y.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Keil, B.; Bianciardi, M.; Triantafyllou, C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [McLaren, D. G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Evans, K. C.; Keil, B.; McLaren, D. G.; Bianciardi, M.; Triantafyllou, C.] Harvard Univ, Sch Med, Boston, MA USA. RI Keil, Boris/P-1411-2014 NR 5 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD AUG PY 2013 VL 111 IS 2 BP 312P EP 312P PG 1 WC Anesthesiology SC Anesthesiology GA 190KF UT WOS:000322337900036 ER PT J AU O'Donnell, E Raje, NS AF O'Donnell, Elizabeth Raje, Noopur S. TI Targeting BRAF in Multiple Myeloma SO CANCER DISCOVERY LA English DT Editorial Material ID PATHOGENESIS; VEMURAFENIB; INHIBITION; MELANOMA; CANCER AB In multiple myeloma, it is believed that multiple mutations in different pathways deregulate the intrinsic biology of the plasma cell, resulting in a genetically complex heterogeneous disease. Mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway have been identified and represent potential targets for therapy in this disease. BRAF, a serine/threonine kinase, has received considerable attention given the success of targeted therapy in malignant melanoma. Andrulis and colleagues report, for the first time, successful treatment of multiple myeloma with vemurafenib, a BRAF inhibitor, in a patient with a BRAF mutation. (C) 2013 AACR. C1 [O'Donnell, Elizabeth; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Raje, NS (reprint author), Massachusetts Gen Hosp, Ctr Multiple Myeloma, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org RI Waha, Andreas/J-2950-2014 NR 11 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2013 VL 3 IS 8 BP 840 EP 842 DI 10.1158/2159-8290.CD-13-0297 PG 3 WC Oncology SC Oncology GA 198XQ UT WOS:000322957600016 PM 23928771 ER PT J AU Liu, Y Marks, K Cowley, GS Carretero, J Liu, QS Nieland, TJF Xu, CX Cohoon, TJ Gao, P Zhang, Y Chen, Z Altabef, AB Tchaicha, JH Wang, XX Choe, S Driggers, EM Zhang, JM Bailey, ST Sharpless, NE Hayes, DN Patel, NM Janne, PA Bardeesy, N Engelman, JA Manning, BD Shaw, RJ Asara, JM Scully, R Kimmelman, A Byers, LA Gibbons, DL Wistuba, II Heymach, JV Kwiatkowski, DJ Kim, WY Kung, AL Gray, NS Root, DE Cantley, LC Wong, KK AF Liu, Yan Marks, Kevin Cowley, Glenn S. Carretero, Julian Liu, Qingsong Nieland, Thomas J. F. Xu, Chunxiao Cohoon, Travis J. Gao, Peng Zhang, Yong Chen, Zhao Altabef, Abigail B. Tchaicha, Jeremy H. Wang, Xiaoxu Choe, Sung Driggers, Edward M. Zhang, Jianming Bailey, Sean T. Sharpless, Norman E. Hayes, D. Neil Patel, Nirali M. Janne, Pasi A. Bardeesy, Nabeel Engelman, Jeffrey A. Manning, Brendan D. Shaw, Reuben J. Asara, John M. Scully, Ralph Kimmelman, Alec Byers, Lauren A. Gibbons, Don L. Wistuba, Ignacio I. Heymach, John V. Kwiatkowski, David J. Kim, William Y. Kung, Andrew L. Gray, Nathanael S. Root, David E. Cantley, Lewis C. Wong, Kwok-Kin TI Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a Target in LKB1-Mutant Lung Cancer SO CANCER DISCOVERY LA English DT Article ID DNA-DAMAGE; THYMIDYLATE KINASE; THYMINELESS DEATH; MASS-SPECTROMETRY; CELL POLARITY; LKB1; PATHWAY; GROWTH; IDENTIFICATION; INACTIVATION AB The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non-small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetically lethal with Lkb1 deficiency in mouse and human lung cancer lines. Global metabolite profiling showed that Lkb1-null cells had a striking decrease in multiple nucleotide metabolites as compared with the Lkb1-wild-type cells. Thus, LKB1-mutant lung cancers have deficits in nucleotide metabolism that confer hypersensitivity to DTYMK inhibition, suggesting that DTYMK is a potential therapeutic target in this aggressive subset of tumors. (C) 2013 AACR. C1 [Liu, Yan; Xu, Chunxiao; Cohoon, Travis J.; Gao, Peng; Zhang, Yong; Chen, Zhao; Altabef, Abigail B.; Tchaicha, Jeremy H.; Wang, Xiaoxu; Janne, Pasi A.; Bardeesy, Nabeel; Engelman, Jeffrey A.; Kimmelman, Alec; Kwiatkowski, David J.; Cantley, Lewis C.; Wong, Kwok-Kin] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Liu, Qingsong; Zhang, Jianming; Gray, Nathanael S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Wang, Xiaoxu; Kimmelman, Alec] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. [Liu, Yan; Xu, Chunxiao; Cohoon, Travis J.; Gao, Peng; Zhang, Yong; Chen, Zhao; Altabef, Abigail B.; Tchaicha, Jeremy H.; Janne, Pasi A.; Kwiatkowski, David J.; Wong, Kwok-Kin] Harvard Univ, Sch Publ Hlth, Dept Med Oncol, Boston, MA 02115 USA. [Liu, Yan; Xu, Chunxiao; Cohoon, Travis J.; Gao, Peng; Chen, Zhao; Altabef, Abigail B.; Tchaicha, Jeremy H.; Janne, Pasi A.; Kwiatkowski, David J.; Wong, Kwok-Kin] Harvard Univ, Sch Publ Hlth, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Liu, Yan; Xu, Chunxiao; Cohoon, Travis J.; Gao, Peng; Chen, Zhao; Altabef, Abigail B.; Tchaicha, Jeremy H.; Wong, Kwok-Kin] Harvard Univ, Sch Publ Hlth, Ludwig Ctr, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Bardeesy, Nabeel; Engelman, Jeffrey A.] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. [Manning, Brendan D.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Marks, Kevin; Choe, Sung; Driggers, Edward M.] Agios Pharmaceut, Cambridge, MA USA. [Cowley, Glenn S.; Nieland, Thomas J. F.; Root, David E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Bailey, Sean T.; Sharpless, Norman E.; Hayes, D. Neil; Patel, Nirali M.; Kim, William Y.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Bailey, Sean T.; Sharpless, Norman E.; Hayes, D. Neil; Patel, Nirali M.; Kim, William Y.] Univ N Carolina, Dept Med & Genet, Chapel Hill, NC 27599 USA. [Shaw, Reuben J.; Scully, Ralph] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA. [Byers, Lauren A.; Gibbons, Don L.; Wistuba, Ignacio I.; Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. [Carretero, Julian] Univ Valencia, Dept Physiol, E-46100 Burjassot, Spain. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dana Bldg 810B,450 Brookline Ave,HIM243, Boston, MA 02115 USA. EM kwong1@partners.org RI Scully, Ralph/F-5008-2013; Cantley, Lewis/D-1800-2014; Carretero, Julian/N-5214-2014 OI liu, qing song/0000-0002-7829-2547; Cantley, Lewis/0000-0002-1298-7653; Kung, Andrew/0000-0002-9091-488X; wong, kwok kin/0000-0001-6323-235X; Carretero, Julian/0000-0001-7269-8506 FU NIH [CA122794, CA140594, CA163896, CA166480, CA154303, Lung SPORE P50CA090578, CA142794]; United against Lung Cancer Foundation; American Lung Association; Susan Spooner Research Fund; Damon Runyon Cancer Research Foundation FX This work is supported by the NIH (CA122794, CA140594, CA163896, CA166480, CA154303, and Lung SPORE P50CA090578), United against Lung Cancer Foundation, American Lung Association, and Susan Spooner Research Fund (to K.-K. Wong); and by NIH CA142794 as well as the Damon Runyon Cancer Research Foundation (to W.Y. Kim). NR 36 TC 28 Z9 28 U1 1 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2013 VL 3 IS 8 BP 870 EP 879 DI 10.1158/2159-8290.CD-13-0015 PG 10 WC Oncology SC Oncology GA 198XQ UT WOS:000322957600021 PM 23715154 ER PT J AU Hollstein, PE Cichowski, K AF Hollstein, Pablo E. Cichowski, Karen TI Identifying the Ubiquitin Ligase Complex that Regulates the NF1 Tumor Suppressor and Ras SO CANCER DISCOVERY LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; DOMAIN PROTEINS; CANCER-THERAPY; E3 LIGASE; INHIBITOR; MUTATIONS; SCF; PATHWAYS; NEUROBLASTOMA; DEGRADATION AB The NF1 tumor suppressor protein neurofibromin is a negative regulator of Ras. Neurofibromin is dynamically regulated by the proteasome, and its degradation and reexpression are essential for maintaining appropriate levels of Ras-GTP. Like p53, NF1/neurofibromin can be inactivated in cancer by both mutations and excessive proteasomal destruction; however, little is known about the mechanisms that underlie this latter process. Here, we show that a Cullin 3 (Cul3)/kelch repeat and BTB domain-containing 7 complex controls both the regulated proteasomal degradation of neurofibromin and the pathogenic destabilization of neurofibromin in glioblastomas. Importantly, RNAi-mediated Cul3 ablation and a dominant-negative Cul3 directly stabilize neurofibromin, suppress Ras and extracellular signal-regulated kinase, and inhibit proliferation in an NF1-dependent manner. Moreover, in glioblastomas where neurofibromin is chronically destabilized, Cul3 inhibition restabilizes the protein and suppresses tumor development. Collectively, these studies show a previously unrecognized role for Cul3 in regulating Ras and provide a molecular framework that can be exploited to develop potential cancer therapies. (C) 2013 AACR. C1 [Hollstein, Pablo E.; Cichowski, Karen] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA. [Hollstein, Pablo E.; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Cichowski, Karen] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. RP Cichowski, K (reprint author), Brigham & Womens Hosp, 77 Ave Louis Pasteur,NRB 0458C, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu FU Department of Defense [W81XWH-08-1-0136]; NCI [R01 CA111754] FX This work was supported by the Department of Defense (W81XWH-08-1-0136) and the NCI (R01 CA111754). NR 50 TC 13 Z9 16 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2013 VL 3 IS 8 BP 880 EP 893 DI 10.1158/2159-8290.CD-13-0146 PG 14 WC Oncology SC Oncology GA 198XQ UT WOS:000322957600022 PM 23661552 ER PT J AU Huo, YY Cai, H Teplova, I Bowman-Colin, C Chen, GH Price, S Barnard, N Ganesan, S Karantza, V White, E Xia, B AF Huo, Yanying Cai, Hong Teplova, Irina Bowman-Colin, Christian Chen, Guanghua Price, Sandy Barnard, Nicola Ganesan, Shridar Karantza, Vassiliki White, Eileen Xia, Bing TI Autophagy Opposes p53-Mediated Tumor Barrier to Facilitate Tumorigenesis in a Model of PALB2-Associated Hereditary Breast Cancer SO CANCER DISCOVERY LA English DT Article ID HOMOLOGOUS RECOMBINATION; SUSCEPTIBILITY GENE; FANCONI-ANEMIA; SUPPRESSES TUMORIGENESIS; BRCA2 DEFICIENCY; TP53 MUTATIONS; PALB2; MICE; P53; INACTIVATION AB Hereditary breast cancers stem from germline mutations in susceptibility genes such as BRCA1, BRCA2, and PALB2, whose products function in the DNA damage response and redox regulation. Autophagy is an intracellular waste disposal and stress mitigation mechanism important for alleviating oxidative stress and DNA damage response activation; it can either suppress or promote cancer, but its role in breast cancer is unknown. Here, we show that similar to Brca1 and Brca2, ablation of Palb2 in the mouse mammary gland resulted in tumor development with long latency, and the tumors harbored mutations in Trp53. Interestingly, impaired autophagy, due to monoallelic loss of the essential autophagy gene Becn1, reduced Palb2-associated mammary tumorigenesis in a Trp53-wild-type but not conditionally null background. These results indicate that, in the face of DNA damage and oxidative stress elicited by PALB2 loss, p53 is a barrier to cancer development, whereas autophagy facilitates cell survival and tumorigenesis. (C) 2013 AACR. C1 [Huo, Yanying; Cai, Hong; Teplova, Irina; Chen, Guanghua; Price, Sandy; Ganesan, Shridar; Karantza, Vassiliki; White, Eileen; Xia, Bing] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Huo, Yanying; Cai, Hong; Xia, Bing] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ USA. [Barnard, Nicola] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pathol, New Brunswick, NJ 08903 USA. [Ganesan, Shridar; Karantza, Vassiliki] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA. [White, Eileen] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08855 USA. [Bowman-Colin, Christian] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Xia, B (reprint author), Rutgers Canc Inst New Jersey, Dept Radiat Oncol, 195 Little Albany St, New Brunswick, NJ 08903 USA. EM xiabi@rutgers.edu FU National Cancer Institute [R01CA138804]; American Cancer Society (RSG) [TBG-119822]; Cancer Institute of New Jersey FX This work was supported by the National Cancer Institute (R01CA138804; to B. Xia), the American Cancer Society (RSG #TBG-119822; to B. Xia), and The Cancer Institute of New Jersey (to B. Xia). NR 48 TC 30 Z9 33 U1 0 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2013 VL 3 IS 8 BP 894 EP 907 DI 10.1158/2159-8290.CD-13-0011 PG 14 WC Oncology SC Oncology GA 198XQ UT WOS:000322957600023 PM 23650262 ER PT J AU Curry, NL Mino-Kenudson, M Oliver, TG Yilmaz, OH Yilmaz, VO Moon, JY Jacks, T Sabatini, DM Kalaany, NY AF Curry, Natasha L. Mino-Kenudson, Mari Oliver, Trudy G. Yilmaz, Oemer H. Yilmaz, Vedat O. Moon, Jade Y. Jacks, Tyler Sabatini, David M. Kalaany, Nada Y. TI Pten-Null Tumors Cohabiting the Same Lung Display Differential AKT Activation and Sensitivity to Dietary Restriction SO CANCER DISCOVERY LA English DT Article ID ONCOGENIC K-RAS; MOUSE MODEL; BREAST-CANCER; INACTIVATION; PROGRESSION; EXPRESSION; EVOLUTION; PATHWAY; GROWTH; GENE AB PTEN loss is considered a biomarker for activated phosphoinositide 3-kinase (PI3K)/AKT, a pathway frequently mutated in cancer, and was recently shown to confer resistance to dietary restriction. Here, we show that Pten loss is not sufficient to drive AKT activation and resistance to dietary restriction in tumors with low growth factor receptor levels. We describe a murine Pten-null Kras-driven lung cancer model that harbors both dietary restriction-resistant, higher-grade, bronchiolar tumors with high AKT activity, and dietary restriction-sensitive, lower-grade, alveolar tumors with low AKT activity. We find that this phenotype is cell autonomous and that normal bronchiolar cells express higher levels of insulin-like growth factor-I receptor (IGF-IR) and of ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5), an endoplasmic reticulum enzyme known to modulate growth factor receptor levels. Suppression of ENTPD5 is sufficient to decrease IGF-IR levels and sensitize bronchiolar tumor cells to serum in vitro and to dietary restriction in vivo. Furthermore, we find that a significant percentage of human non-small cell lung carcinomas (NSCLC) have low AKT activity despite PTEN loss. (C) 2013 AACR. C1 [Curry, Natasha L.; Yilmaz, Vedat O.; Moon, Jade Y.; Kalaany, Nada Y.] Boston Childrens Hosp, Div Endocrinol, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Mino-Kenudson, Mari; Yilmaz, Oemer H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Yilmaz, Oemer H.] Harvard Univ, Sch Med, Boston, MA USA. [Kalaany, Nada Y.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Oliver, Trudy G.; Jacks, Tyler; Sabatini, David M.] Howard Hughes Med Inst, Cambridge, MA USA. [Oliver, Trudy G.; Jacks, Tyler; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA USA. [Oliver, Trudy G.; Jacks, Tyler; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Yilmaz, Oemer H.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Kalaany, NY (reprint author), Boston Childrens Hosp, Div Endocrinol, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. EM nada.kalaany@childrens.harvard.edu FU Anna Fuller Fund fellowship; Boston Children's Hospital; Alexander and Margaret Stewart Trust; David H. Koch Cancer Research Award; NIH [R01 AI047389, R01 CA129105, 2-P30-CA14051] FX This research was supported by the Anna Fuller Fund fellowship (to N.Y. Kalaany); Boston Children's Hospital (to N.Y. Kalaany, N.L. Curry, and V.O. Yilmaz); the Alexander and Margaret Stewart Trust Award (to D.M. Sabatini); the David H. Koch Cancer Research Award (to D.M. Sabatini); and NIH grants R01 AI047389, R01 CA129105 (to D.M. Sabatini), and 2-P30-CA14051 (to D. M. Sabatini, T. Jacks, and T.G. Oliver). D.M. Sabatini is an investigator of the Howard Hughes Medical Institute. NR 30 TC 13 Z9 15 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2013 VL 3 IS 8 BP 908 EP 921 DI 10.1158/2159-8290.CD-12-0507 PG 14 WC Oncology SC Oncology GA 198XQ UT WOS:000322957600024 PM 23719831 ER PT J AU Castano, Z Marsh, T Tadipatri, R Kuznetsov, HS Al-Shahrour, F Paktinat, M Greene-Colozzi, A Nilsson, B Richardson, AL McAllister, SS AF Castano, Zafira Marsh, Timothy Tadipatri, Ramya Kuznetsov, Hanna S. Al-Shahrour, Fatima Paktinat, Mahnaz Greene-Colozzi, April Nilsson, Bjorn Richardson, Andrea L. McAllister, Sandra S. TI Stromal EGF and IGF-I Together Modulate Plasticity of Disseminated Triple-Negative Breast Tumors SO CANCER DISCOVERY LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; CANCER CELLS; STEM-CELLS; ACQUIRED-RESISTANCE; GROWTH; INSULIN; RECEPTOR; MYC; PROGRESSION; MACROENVIRONMENT AB The causes for malignant progression of disseminated tumors and the reasons recurrence rates differ in women with different breast cancer subtypes are unknown. Here, we report novel mechanisms of tumor plasticity that are mandated by microenvironmental factors and show that recurrence rates are not strictly due to cell-intrinsic properties. Specifically, outgrowth of the same population of incipient tumors is accelerated in mice with triple-negative breast cancer (TNBC) relative to those with luminal breast cancer. Systemic signals provided by overt TNBCs cause the formation of a tumor-supportive microenvironment enriched for EGF and insulin-like growth factor-I (IGF-I) at distant indolent tumor sites. Bioavailability of EGF and IGF-I enhances the expression of transcription factors associated with pluripotency, proliferation, and epithelial-mesenchymal transition. Combinatorial therapy with EGF receptor and IGF-I receptor inhibitors prevents malignant progression. These results suggest that plasticity and recurrence rates can be dictated by host systemic factors and offer novel therapeutic potential for patients with TNBC. (C) 2013 AACR. C1 [Castano, Zafira; Marsh, Timothy; Tadipatri, Ramya; Kuznetsov, Hanna S.; Al-Shahrour, Fatima; Paktinat, Mahnaz; McAllister, Sandra S.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Castano, Zafira; McAllister, Sandra S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Greene-Colozzi, April; Richardson, Andrea L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Al-Shahrour, Fatima; Nilsson, Bjorn; McAllister, Sandra S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [McAllister, Sandra S.] Harvard Stem Cell Inst, Cambridge, MA USA. [Nilsson, Bjorn] Lund Univ, Dept Lab Med, Div Hematol & Transfus Med, Lund, Sweden. RP McAllister, SS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 1 Blackfan Circle,Karp 5-214, Boston, MA 02115 USA. EM smcallister1@partners.org RI McAllister, Sandra/J-7373-2012 FU Harvard Stem Cell Institute; American Cancer Society; NIH [RO1 CA166284-01]; Dana-Farber/Harvard SPORE in Breast Cancer [2 P50 CA89393-06] FX This work was supported by funds from the Harvard Stem Cell Institute, the American Cancer Society, and NIH RO1 CA166284-01 (to S.S. McAllister), and partially supported by the Dana-Farber/Harvard SPORE in Breast Cancer (N.C.I., 2 P50 CA89393-06; to A.L. Richardson). NR 49 TC 17 Z9 17 U1 2 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2013 VL 3 IS 8 BP 922 EP 935 DI 10.1158/2159-8290.CD-13-0041 PG 14 WC Oncology SC Oncology GA 198XQ UT WOS:000322957600025 PM 23689072 ER PT J AU Janzen, DM Rosales, MA Paik, DY Lee, DS Smith, DA Witte, ON Iruela-Arispe, ML Memarzadeh, S AF Janzen, Deanna M. Rosales, Miguel A. Paik, Daniel Y. Lee, Daniel S. Smith, Daniel A. Witte, Owen N. Iruela-Arispe, M. Luisa Memarzadeh, Sanaz TI Progesterone Receptor Signaling in the Microenvironment of Endometrial Cancer Influences Its Response to Hormonal Therapy SO CANCER RESEARCH LA English DT Article ID UTERINE EPITHELIUM; ANDROGEN RECEPTOR; PROSTATE-CANCER; BREAST-CANCER; ESTROGEN; CARCINOMA; HYPERPLASIA; EXPRESSION; MOUSE; ADENOCARCINOMA AB Progesterone, an agonist for the progesterone receptor (PR), can be an efficacious and well-tolerated treatment in endometrial cancer. The clinical use of progesterone is limited because of the lack of biomarkers that predict hormone sensitivity. Despite its efficacy in cancer therapy, mechanisms and site of action for progesterone remain unknown. Using an in vivo endometrial cancer mouse model driven by clinically relevant genetic changes but dichotomous responses to hormonal therapy, we show that signaling through stromal PR is necessary and sufficient for progesterone antitumor effects. Endometrial cancers resulting from epithelial loss of PTEN (PTENKO) were hormone sensitive and had abundant expression of stromal PR. Stromal deletion of PR as a single genetic change in these tumors induced progesterone resistance indicating that paracrine signaling through the stroma is essential for the progesterone therapeutic effects. A hormone-refractory endometrial tumor with low levels of stromal PR developed when activation of KRAS was coupled with PTEN-loss (PTENKO/Kras). The innate progesterone resistance in PTENKO/Kras tumors stemmed from methylation of PR in the tumor microenvironment. Add-back of stromal PR expressed from a constitutively active promoter sensitized these tumors to progesterone therapy. Results show that signaling through stromal PR is sufficient for inducing hormone responsiveness. Our findings suggest that epigenetic derepression of stromal PR could be a potential therapeutic target for sensitizing hormone-refractory endometrial tumors to progesterone therapy. On the basis of these results, stromal expression of PR may emerge as a reliable biomarker in predicting response to hormonal therapy. (C)2013 AACR. C1 [Janzen, Deanna M.; Rosales, Miguel A.; Paik, Daniel Y.; Lee, Daniel S.; Memarzadeh, Sanaz] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Witte, Owen N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Iruela-Arispe, M. Luisa] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Smith, Daniel A.; Witte, Owen N.; Iruela-Arispe, M. Luisa] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Witte, Owen N.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. [Witte, Owen N.; Memarzadeh, Sanaz] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA. [Smith, Daniel A.; Witte, Owen N.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Memarzadeh, Sanaz] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Memarzadeh, S (reprint author), Univ Calif Los Angeles, 555 Westwood Plaza,Level B,Box 957243,1015 Terasa, Los Angeles, CA 90095 USA. EM smemarzadeh@mednet.ucla.edu FU VA CDA-2 Award; Scholars in Translational Medicine Program; Mary Kay Award; CDU/UCLA NIH/NCI [U54-CA-143931]; Sidney Kimmel Foundation; UCLA Cancer Research Coordinating Committee; Concern foundation FX S. Memarzadeh is supported by a VA CDA-2 Award, Scholars in Translational Medicine Program, Mary Kay Award, the CDU/UCLA NIH/NCI Grant #U54-CA-143931 award, a Sidney Kimmel Foundation award, the UCLA Cancer Research Coordinating Committee grant, and the Concern foundation. NR 49 TC 12 Z9 15 U1 1 U2 8 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 AUG 1 PY 2013 VL 73 IS 15 BP 4697 EP 4710 DI 10.1158/0008-5472.CAN-13-0930 PG 14 WC Oncology SC Oncology GA 194HC UT WOS:000322620800012 PM 23744837 ER PT J AU Tworoger, SS Eliassen, AH Zhang, XH Qian, J Sluss, PM Rosner, BA Hankinson, SE AF Tworoger, Shelley S. Eliassen, A. Heather Zhang, Xuehong Qian, Jing Sluss, Patrick M. Rosner, Bernard A. Hankinson, Susan E. TI A 20-Year Prospective Study of Plasma Prolactin as a Risk Marker of Breast Cancer Development SO CANCER RESEARCH LA English DT Article ID POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR; STEROID-HORMONES; CELLS; GROWTH; BLOOD; REPRODUCIBILITY; ANGIOGENESIS; ACTIVATION AB Understanding how the timing of exposure to endogenous hormones influences cancer development is critical to elucidating disease etiology. Prolactin increases proliferation and cell motility, processes important in later stage tumor development, suggesting that levels proximate (versus distant) to diagnosis may better predict risk. Thus, we calculated relative risks (RR) and 95% confidence intervals (CI) for prolactin levels on samples collected <10 (proximate) versus >= 10 (distant) years before diagnosis in the Nurses' Health Study (NHS) and NHSII with breast cancer risk, including in a subset of NHS women providing two samples 10 years apart. We measured prolactin via immunoassay in cases diagnosed from 1990 to 2010 (NHS) and 1999 to 2009 (NHSII) and matched controls. Overall, 2,468 cases and 4,021 controls had prolactin measured <10 years and 953 cases and 1,339 controls >10 years before diagnosis/reference date. There was an increased risk for higher proximate prolactin levels [RR, >15.7 vs. <= 8.1 ng/mL (i.e., top vs. bottom quartiles) = 1.20; 95% CI, 1.03-1.40; P-trend = 0.005], but not for distant levels (RR = 0.97; P-trend = 0.94); results were similar among women with two blood samples (P-interaction, proximate vs. distant = 0.07). The positive association was stronger for ER+ disease (RR = 1.28; P-trend = 0.003) and postmenopausal women (RR = 1.37; P-trend = 0.0002). Among postmenopausal women, the association was strongest for ER+ disease (RR = 1.52) and lymph node-positive cases (RR = 1.63). Our data suggest that prolactin levels measured <10 years before diagnosis are most strongly associated with postmenopausal breast cancer risk, especially for ER+ tumors and metastatic disease. This corresponds with biologic data that prolactin is etiologically important in tumor promotion. (C)2013 AACR. C1 [Tworoger, Shelley S.; Eliassen, A. Heather; Zhang, Xuehong; Rosner, Bernard A.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Tworoger, Shelley S.; Eliassen, A. Heather; Zhang, Xuehong; Rosner, Bernard A.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Tworoger, Shelley S.; Eliassen, A. Heather; Zhang, Xuehong; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Qian, Jing; Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Boston, MA 02125 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Tworoger, SS (reprint author), Brigham & Womens Hosp, 181 Longwood Ave,3rd Fl, Boston, MA 02115 USA. EM nhsst@channing.harvard.edu OI Tworoger, Shelley/0000-0002-6986-7046 FU NIH [R01 CA138580, R01 CA49449, R01 CA67262, R01 CA50385, P01 CA87969] FX This work was financially supported by the NIH (grant nos. R01 CA138580, R01 CA49449, R01 CA67262, R01 CA50385, P01 CA87969). NR 38 TC 50 Z9 51 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2013 VL 73 IS 15 BP 4810 EP 4819 DI 10.1158/0008-5472.CAN-13-0665 PG 10 WC Oncology SC Oncology GA 194HC UT WOS:000322620800022 PM 23783576 ER PT J AU Antony, R Emery, CM Sawyer, AM Garraway, LA AF Antony, Rajee Emery, Caroline M. Sawyer, Allison M. Garraway, Levi A. TI C-RAF Mutations Confer Resistance to RAF Inhibitors SO CANCER RESEARCH LA English DT Article ID B-RAF; WILD-TYPE; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; KINASE-ACTIVITY; HUMAN CANCER; BRAF; ACTIVATION; PATHWAY; CRAF AB Melanomas that contain B-RAF(V600E) mutations respond transiently to RAF and MEK inhibitors; however, resistance to these agents remains a formidable challenge. Although B- or C-RAF dysregulation represents prominent resistance mechanisms, resistance-associated point mutations in RAF oncoproteins are surprisingly rare. To gain insights herein, we conducted random mutagenesis screens to identify B- or C-RAF mutations that confer resistance to RAF inhibitors. Whereas bona fide B-RAF(V600E) resistance alleles were rarely observed, we identified multiple C-RAF mutations that produced biochemical and pharmacologic resistance. Potent C-RAF resistance alleles localized to a 14-3-3 consensus binding site or a separate site within the P loop. These mutations elicited paradoxical upregulation of RAF kinase activity in a dimerization-dependent manner following exposure to RAF inhibitors. Knowledge of resistance-associated C-RAF mutations may enhance biochemical understanding of RAF-dependent signaling, anticipate clinical resistance to novel RAF inhibitors, and guide the design of "next-generation" inhibitors for deployment in RAF- or RAS-driven malignancies. (C)2013 AACR. C1 [Antony, Rajee; Emery, Caroline M.; Sawyer, Allison M.; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Antony, Rajee; Emery, Caroline M.; Sawyer, Allison M.; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Garraway, Levi A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu FU Novartis Institute for BioMedical Research FX This study is supported by a grant from Novartis Institute for BioMedical Research. NR 46 TC 15 Z9 15 U1 6 U2 15 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 AUG 1 PY 2013 VL 73 IS 15 BP 4840 EP 4851 DI 10.1158/0008-5472.CAN-12-4089 PG 12 WC Oncology SC Oncology GA 194HC UT WOS:000322620800025 PM 23737487 ER PT J AU Yonetsu, T Bouma, BE Kato, K Fujimoto, JG Jang, IK AF Yonetsu, Taishi Bouma, Brett E. Kato, Koji Fujimoto, James G. Jang, Ik-Kyung TI Optical Coherence Tomography - 15 Years in Cardiology SO CIRCULATION JOURNAL LA English DT Review DE Coronary artery disease; Optical coherence tomography; Percutaneous coronary intervention ID ACUTE CORONARY SYNDROME; ELUTING STENT IMPLANTATION; ACUTE MYOCARDIAL-INFARCTION; FIBROUS CAP THICKNESS; BARE-METAL STENTS; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; NEOINTIMAL COVERAGE; PULMONARY-HYPERTENSION; ARTERY-DISEASE AB Since its invention in the late 1990s, intravascular optical coherence tomography (OCT) has been rapidly adopted in clinical research and, more recently, in clinical practice. Given its unprecedented resolution and high image contrast, OCT has been used to visualize plaque characteristics and to evaluate the vascular response to percutaneous coronary intervention. In particular, OCT is becoming the standard modality to evaluate in vivo plaque vulnerability, including the presence of lipid content, thin fibrous cap, or macrophage accumulation. Furthermore, OCT findings after stent implantation, such as strut apposition, neointimal hyperplasia, strut coverage, and neoatherosclerosis, are used as surrogate markers of the vascular response. New applications for OCT are being explored, such as transplant vasculopathy or non-coronary vascular imaging. Although OCT has contributed to cardiovascular research by providing a better understanding of the pathophysiology of coronary artery disease, data linking the images and clinical outcomes are lacking. Prospective data are needed to prove that the use of OCT improves patient outcomes, which is the ultimate goal of any clinical diagnostic tool. C1 [Yonetsu, Taishi; Kato, Koji; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org FU LightLab Imaging/St. Jude Medical FX Dr IK Jang received a research grant and consulting fee from LightLab Imaging/St. Jude Medical. NR 82 TC 28 Z9 29 U1 2 U2 14 PU JAPANESE CIRCULATION SOC PI TOYKO PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO, 100-0011, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD AUG PY 2013 VL 77 IS 8 BP 1933 EP 1940 DI 10.1253/circj.CJ-13-0643.1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 196CW UT WOS:000322752000002 PM 23856651 ER PT J AU Lopez-Cuenca, A Manzano-Fernandez, S Marin, F Parra-Pallares, S Navarro-Penalver, M Montalban-Larrea, S Andreu-Cayuelas, JM Romero-Aniorte, AI Aviles-Plaza, F Valdes-Chavarri, M Januzzi, JL AF Lopez-Cuenca, Angel Manzano-Fernandez, Sergio Marin, Francisco Parra-Pallares, Soledad Navarro-Penalver, Marina Montalban-Larrea, Salvador Andreu-Cayuelas, Jose M. Romero-Aniorte, Ana I. Aviles-Plaza, Francisco Valdes-Chavarri, Mariano Januzzi, James L., Jr. TI Beta-Trace Protein and Cystatin C as Predictors of Major Bleeding in Non-ST-Segment Elevation Acute Coronary Syndrome SO CIRCULATION JOURNAL LA English DT Article DE Acute coronary syndrome; Beta-trace protein; Hemorrhage ID GLOMERULAR-FILTRATION-RATE; MYOCARDIAL-INFARCTION; SERUM CREATININE; OUTCOMES; EVENTS; RISK; MORTALITY; EQUATION; FAILURE; ANGINA AB Background: Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. We assessed the ability of both to predict major bleeding (MB) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), compared to other renal function parameters and clinical risk scores. Methods and Results: We included 273 patients. Blood samples were obtained within 24h of admission. The end-point was MB. During a follow-up of 760 days (411-1,098 days), 25 patients (9.2%) had MB. Patients with MB had higher concentrations of BTP (0.98 mg/L; 0.71-1.16 mg/L vs. 0.72 mg/L, 0.60-0.91 mg/L, P=0.002), CysC (1.05 mg/L; 0.91-1.30 mg/L vs. 0.90 mg/L, 0.75-1.08 mg/L, P=0.003), higher CRUSADE score (39 +/- 16 points vs. 29 +/- 15 points, P=0.002) and lower estimated glomerular filtration rate (eGFR; 66 +/- 27 vs. 80 +/- 30 ml .min(-1). 1.73 m(-2), P=0.02) than patients without MB; there was no difference in creatinine level between the groups (P=0.14). After multivariable adjustment, both were predictors of MB, while eGFR and creatinine did not achieve statistical significance. Among subjects with eGFR >60 ml .min(-1). 1.73 m(-2), those with elevated concentrations of both biomarkers had a significantly higher risk for MB. Net reclassification indexes from the addition of BTP and CysC to CRUSADE risk score were 38% and 21% respectively, while the relative integrated discrimination indexes were 12.5% and 3.8%. Conclusions: Among NSTE-ACS patients, BTP and CysC were superior to conventional renal parameters for predicting MB, and improved clinical stratification for hemorrhagic risk. C1 [Lopez-Cuenca, Angel; Manzano-Fernandez, Sergio; Marin, Francisco; Navarro-Penalver, Marina; Montalban-Larrea, Salvador; Andreu-Cayuelas, Jose M.; Romero-Aniorte, Ana I.; Valdes-Chavarri, Mariano] Univ Hosp Virgen Arrixaca, Div Cardiol, Murcia, Spain. [Manzano-Fernandez, Sergio; Marin, Francisco; Valdes-Chavarri, Mariano] Univ Murcia, Murcia, Spain. [Parra-Pallares, Soledad; Aviles-Plaza, Francisco] Univ Hosp Virgen Arrixaca, Dept Biochem, Murcia, Spain. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 24 TC 4 Z9 5 U1 0 U2 4 PU JAPANESE CIRCULATION SOC PI TOYKO PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO, 100-0011, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD AUG PY 2013 VL 77 IS 8 BP 2088 EP 2096 DI 10.1253/circj.CJ-13-0106 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 196CW UT WOS:000322752000027 PM 23698027 ER PT J AU Ananthakrishnan, AN Long, MD Martin, CF Sandler, RS Kappelman, MD AF Ananthakrishnan, Ashwin N. Long, Millie D. Martin, Christopher F. Sandler, Robert S. Kappelman, Michael D. TI Sleep Disturbance and Risk of Active Disease in Patients With Crohn's Disease and Ulcerative Colitis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Intestinal Inflammation; Environment; PROMIS; Prospective Cohort Study ID INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; METABOLIC SYNDROME; ACTIVITY INDEX; FATIGUE; INTERLEUKIN-6; EPIDEMIOLOGY; DISABILITY; DEPRESSION AB BACKGROUND & AIMS: Impairment of sleep quality is common in patients with inflammatory bowel diseases (IBDs) (eg, Crohn's disease [CD] and ulcerative colitis [UC]), even during clinical remission. Sleep impairment can activate inflammatory pathways. Few prospective studies have examined the role of sleep disturbance on risk of relapse in IBD. METHODS: We analyzed data from 3173 patients with IBD (1798 in clinical remission at baseline) participating in the Crohn's and Colitis Foundation of America Partners study, a longitudinal, Internet-based cohort. Sleep disturbance was measured using a subset of questions from the Patient Reported Outcomes Measurement Information Systems sleep disturbance questionnaire. Disease activity was assessed using the short Crohn's Disease Activity Index and the simple clinical colitis activity index for CD and UC, respectively. Logistic regression was used to identify predictors of sleep quality and examine the effect of sleep quality at baseline among patients in remission on risk of active disease at 6 months. RESULTS: Disease activity, depression, female sex, smoking, and use of corticosteroids or narcotics were associated with sleep disturbance at enrollment. Among 1291 patients whose CD was in remission at baseline, those with impaired sleep had a 2-fold increase in risk of active disease at 6 months (adjusted odds ratio, 2.00; 95% confidence interval, 1.45-2.76); however, no effect was observed in patients with UC (odds ratio, 1.14; 95% confidence interval, 0.75-1.74). These findings persisted in a number of sensitivity analyses. CONCLUSIONS: Sleep disturbance was associated with an increased risk of disease flares in CD but not UC. These findings indicate that the evaluation and treatment of sleep disturbance in patients with CD might improve outcomes. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Long, Millie D.; Martin, Christopher F.; Sandler, Robert S.] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Kappelman, Michael D.] Univ N Carolina, Dept Pediat, Div Gastroenterol, Chapel Hill, NC 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, P30 DK34987]; Crohn's and Colitis Foundation of America FX Supported in part by a grant from the National Institutes of Health (K23 DK097142 to A.N.A.), and the Crohn's and Colitis Foundation of America Partners cohort is supported by grants from the Crohn's and Colitis Foundation of America and the National Institutes of Health (P30 DK34987). NR 41 TC 37 Z9 38 U1 6 U2 17 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 AUG PY 2013 VL 11 IS 8 BP 965 EP 971 DI 10.1016/j.cgh.2013.01.021 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 195MP UT WOS:000322707100017 PM 23376797 ER PT J AU Kaufman, JL Fabre, C Lonial, S Richardson, PG AF Kaufman, Jonathan L. Fabre, Claire Lonial, Sagar Richardson, Paul G. TI Histone Deacetylase Inhibitors in Multiple Myeloma: Rationale and Evidence for Their Use in Combination Therapy SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Review DE Hematologic malignancy; Histone modification; Immunomodulatory agent; Proteasome inhibitor ID UNFOLDED PROTEIN RESPONSE; PHASE-I TRIAL; PROTEASOME INHIBITION; PANOBINOSTAT LBH589; ORAL VORINOSTAT; HDAC INHIBITORS; CANCER-THERAPY; BORTEZOMIB; CELLS; APOPTOSIS AB Multiple myeloma (MM) arises from abnormal proliferation and survival (ie, a high proliferative index and a low apoptotic index) of mature immunoglobulin-producing plasma cells in the bone marrow. Development of novel therapeutic options, such as proteasome inhibitors and immunomodulatory agents (IMiDs), has improved treatment outcomes. However, patients often develop relapsed and refractory MM, thus requiring alternative treatment approaches. Histone acetyltransferases and histone deacetylases (HDACs) control the acetylation status of proteins and affect a broad array of physiologic processes (eg, cell cycle, apoptosis, and protein folding) involved in cell growth and survival. The discovery that HDACs might have a role in various hematologic malignancies, including MM, has led to the development of HDAC inhibitors as potential antitumor agents. Preclinical evidence from studies of HDAC inhibitors in combination with proteasome inhibitors (eg, bortezomib and carfilzomib), other antimyeloma agents, including IMiDs (eg, lenalidomide), and cytotoxic agents (eg, melphalan, pegylated liposomal doxorubicin), provides a strong scientific rationale for the evaluation of these regimens. Results from early stage clinical trials further support the use of HDAC inhibitors as a therapeutic option for MM, in combination with current and emerging antimyeloma agents. In this review, we examine the role of protein acetylation that underlies the antimyeloma effects of HDAC inhibitors, discuss the preclinical rationale for the use of HDAC inhibitors in combination with other antimyeloma agents, and provide an overview of the current clinical evidence supporting the use of HDAC inhibitors as a therapeutic option in MM. (C) 2013 Elsevier Inc. All rights reserved. C1 [Kaufman, Jonathan L.; Lonial, Sagar] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Fabre, Claire; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaufman, JL (reprint author), Emory Univ, Winship Canc Ctr, Dept Hematol & Med Oncol, 1365-C Clifton Rd NE, Atlanta, GA 30322 USA. EM jlkaufm@emory.edu FU Merck Sharp & Dohme Corp, a subsidiary of Merck Co, Inc. FX Editorial assistance was provided by Joseph J. Abrajano, PhD, and Georgia Gleason, PhD, of Integrus Scientific, a division of Medicus International New York. This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc. NR 78 TC 23 Z9 24 U1 0 U2 16 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD AUG PY 2013 VL 13 IS 4 BP 370 EP 376 DI 10.1016/j.clml.2013.03.016 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 200QW UT WOS:000323085000003 PM 23787122 ER PT J AU Trummer, M Eustacchio, S Barth, M Klassen, PD Stein, S AF Trummer, Martin Eustacchio, Sandro Barth, Martin Klassen, Peter Douglas Stein, Shlomit TI Protecting facet joints post-lumbar discectomy: Barricaid annular closure device reduces risk of facet degeneration SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Lumbar; Discectomy; Facet joint; Facet degeneration; Facet arthrosis; Annulus fibrosis; Disc herniation; Annular closure device ID LUMBAR DISKECTOMY; DISC HERNIATION; BACK-PAIN; OSTEOARTHRITIS; REPLACEMENT; RADICULOPATHY; PREVALENCE; ARTHROSIS; SURGERY; LEVEL AB Lumbar discectomy is an effective treatment for lumbar disc herniation (LDH). Although the majority of patients experience successful outcomes, a significant fraction will experience a recurrence of their back pain due to facet joint degeneration. Facet joint degeneration after discectomy may be the result of excessive nuclear removal, disc space narrowing, and annular injury. This study investigated whether implantation with the Barricaid annular closure device (ACD) during discectomy reduced the rate of facet degeneration. Inclusion criteria were primary lumbar disc herniation failing conservative treatment, Visual Analog Scale (VAS) Leg >= 40/100, Oswestry Disability Index (ODI) >= 40/100 and defects that were <= 60 mm(2) (Barricaid arm only), and patient age 18-75. CT interpretations were collected preoperatively and 12 months post-discectomy. Patients implanted with Barricaid had significantly reduced rates and grades of facet degeneration than patients without Barricaid. Reinforcing the annulus fibrosus with Barricaid during lumbar discectomy may slow the progression of facet joint degeneration. (C) 2013 Elsevier B.V. All rights reserved. C1 [Trummer, Martin; Eustacchio, Sandro] Med Univ, Graz, Austria. [Barth, Martin] Univ Med Mannheim, Dept Neurosurg, Mannheim, Germany. [Klassen, Peter Douglas] St Bonifatius Hosp, Dept Neurosurg, Lingen, Germany. [Stein, Shlomit] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Trummer, M (reprint author), LKH Graz, Auenbrugger Pl 1, A-8036 Graz, Austria. EM martin.trummer@klinikum-graz.at RI Barth, Martin/E-8265-2014 FU Intrinsic Therapeutics, Inc. FX Funding for this research was provided in part by Intrinsic Therapeutics, Inc. NR 29 TC 7 Z9 8 U1 5 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD AUG PY 2013 VL 115 IS 8 BP 1440 EP 1445 DI 10.1016/j.clineuro.2013.01.007 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 198NJ UT WOS:000322929300045 PM 23473658 ER PT J AU Pulsipher, DT Stricker, NH Sadek, JR Haaland, KY AF Pulsipher, Dalin T. Stricker, Nikki H. Sadek, Joseph R. Haaland, Kathleen Y. TI Clinical Utility of the Neuropsychological Assessment Battery (NAB) after Unilateral Stroke SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Unilateral stroke; NAB; Clinical utility; Lateralized ID MILD COGNITIVE IMPAIRMENT; TRAUMATIC BRAIN-INJURY; ATTENTION DEFICITS; SCREENING MODULE; LEFT-HEMISPHERE; DISCONNEXION SYNDROMES; FUNCTIONAL RECOVERY; NATURAL-HISTORY; ISCHEMIC-STROKE; TEMPORAL-LOBE AB The NAB is a comprehensive battery assessing five cognitive domains (Attention, Language, Memory, Spatial, Executive Function). Despite the advantage of co-normative domain data, its clinical utility is not well established because few studies have reported full-battery findings. The aim of this study was to determine if the NAB was sensitive to well documented hemispheric differences in language and spatial skills after unilateral stroke. We compared demographically matched control participants (n = 52) and individuals after left (LHD, n = 36) or right (RHD, n = 33) hemisphere damage due to stroke on the NAB, parts of the Western Aphasia Battery, and traditional visuospatial tasks. Both stroke groups showed impaired NAB Attention, Spatial, and Executive Functions relative to controls, while the LHD group was more impaired than control and RHD groups on Language and Memory modules. LHD patients with aphasia on traditional measures performed worse than control and non-aphasic LHD patients on all NAB domains. RHD patients with spatial impairment on traditional measures performed worse than controls, but not RHD patients without spatial impairment, on the NAB Spatial domain. Findings suggest the NAB is generally comparable to traditional language and visuospatial measures, and it sufficiently detects attention and executive deficits. C1 [Pulsipher, Dalin T.; Sadek, Joseph R.; Haaland, Kathleen Y.] New Mexico VA Hlth Care Syst, Behav Hlth Care Line 116, Albuquerque, NM USA. [Stricker, Nikki H.] VA Boston Healthcare Syst, Boston, MA USA. [Stricker, Nikki H.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Sadek, Joseph R.; Haaland, Kathleen Y.] Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA. [Haaland, Kathleen Y.] New Mexico VA Hlth Care Syst, Res Serv, Albuquerque, NM USA. [Haaland, Kathleen Y.] Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. RP Haaland, KY (reprint author), VA Med Ctr, Psychol Serv, 116B, Albuquerque, NM 87108 USA. EM dpulsipher@chmca.org; khaaland@unm.edu FU Department of Veterans Affairs; Office of Research and Development, Clinical Sciences Research and Development; Rehabilitation Research and Development Merit grant FX This material is based upon work supported in part by the Department of Veterans Affairs, Office of Research and Development, Clinical Sciences Research and Development Merit grant and Career Scientist Award (to KYH) and Rehabilitation Research and Development Merit grant (to KYH). NR 84 TC 4 Z9 4 U1 1 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD AUG 1 PY 2013 VL 27 IS 6 BP 924 EP 945 DI 10.1080/13854046.2013.799714 PG 22 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 197RA UT WOS:000322867100003 PM 23682731 ER PT J AU Maw, TT Fried, L AF Maw, Thin Thin Fried, Linda TI Chronic Kidney Disease in the Elderly SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Elderly; Geriatric; Chronic kidney disease; Renal function; Dialysis ID GLOMERULAR-FILTRATION-RATE; CHRONIC RENAL-INSUFFICIENCY; BONE-MINERAL DENSITY; BLOOD-PRESSURE; CYSTATIN-C; CARDIOVASCULAR OUTCOMES; SERUM CREATININE; UNITED-STATES; OLDER INDIVIDUALS; GLUCOSE CONTROL AB Chronic kidney disease (CKD) is increasingly being recognized as a disease of elderly individuals. In recent years the definition and categorization of kidney disease has been standardized. There are concerns that this standardization has led to an increase in the number of older individuals labeled as having CKD. This article addresses the definitions of CKD, recently published revised CKD stages with risk stratifications, and limitations of using formulas to assess renal function in the elderly. Also discussed are management of common risk factors of progression CKD, nonrenal-related outcomes, prognosis of CKD in older individuals, and criteria for referral to nephrology. C1 [Maw, Thin Thin; Fried, Linda] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. [Fried, Linda] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. RP Fried, L (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, 3550 Terrace St, Pittsburgh, PA 15261 USA. EM linda.fried@va.gov NR 57 TC 6 Z9 6 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2013 VL 29 IS 3 BP 611 EP + DI 10.1016/j.cger.2013.05.003 PG 15 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 198MY UT WOS:000322928200006 PM 23849011 ER PT J AU Kim, SJ Lee, H Cho, JM Park, CB Kim, W Kato, K Yonetsu, T Kim, CJ Jang, IK AF Kim, Soo-Joong Lee, Hang Cho, Jin-Man Park, Chang-Bum Kim, Weon Kato, Koji Yonetsu, Taishi Kim, Chong-Jin Jang, Ik-Kyung TI Comparison of zotarolimus-eluting stent and everolimus-eluting stent for vascular healing response: serial 3-month and 12-month optical coherence tomography study SO CORONARY ARTERY DISEASE LA English DT Article DE everolimus-eluting stent; malapposition; neointimal coverage; optical coherence tomography; zotarolimus-eluting stent ID POLYESTER ARTERIAL PROSTHESES; FOLLOW-UP; NEOINTIMAL COVERAGE; CORONARY STENTS; RANDOMIZED-TRIALS; BARE-METAL; IMPLANTATION; THROMBOSIS; FLUOROPASSIVATION; METAANALYSIS AB Background Everolimus-eluting stents (EES) have shown favorable clinical outcomes. However, there have been no studies evaluating early vascular response after EES implantation. We designed a prospective study to compare the neointimal response between zotarolimus-eluting stents (ZES) and EES at 3 and 12 months using serial optical coherence tomography examinations.Methods and results Sixty patients who underwent 3-month and 12-month follow-up optical coherence tomography (36 EES, 24 ZES) were included. Neointimal coverage and malapposition were evaluated using a strut-based analysis at both 3 and 12 months. Neointimal hyperplasia area and thrombus were assessed. ZES showed a higher incidence of covered struts (81.5 vs. 77.1%, P<0.0001) and lower incidence of malapposed struts (1.4 vs. 2.3%, P=0.001) than EES at 3 months. However, at 12 months, EES showed a slightly higher incidence of covered struts (96.4 vs. 93.6%, P<0.0001) and a lower incidence of malapposed struts (0.9 vs. 1.1%, P=0.03) than ZES. Neointimal hyperplasia area was greater in the ZES group than in the EES group at both 3 and 12 months (0.77 vs. 0.49 mm(2), P=0.03 and 1.50 vs. 0.97 mm(2), P=0.01, respectively). No significant difference in the incidence of thrombus was observed at both 3 and 12 months.Conclusion ZES showed rapid neointimal healing compared with EES at 3 months. However, at 12 months, EES had a slightly better vascular healing profile than ZES. C1 [Kim, Soo-Joong; Kato, Koji; Yonetsu, Taishi; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Boston, MA USA. [Kim, Soo-Joong; Cho, Jin-Man; Park, Chang-Bum; Kim, Weon; Kim, Chong-Jin] Kyung Hee Univ, Dept Internal Med, Div Cardiol, Coll Med, Seoul, South Korea. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org FU Medtronic Inc., Santa Rosa, CA, USA FX This study was supported by Medtronic Inc., Santa Rosa, CA, USA. NR 34 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD AUG PY 2013 VL 24 IS 5 BP 431 EP 439 DI 10.1097/MCA.0b013e328362b2e7 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 202NZ UT WOS:000323225700015 PM 23722649 ER PT J AU Nguyen, HM Graber, CJ AF Nguyen, Hien M. Graber, Christopher J. TI Cephalothin susceptibility testing as class representative for oral cephalosporins: is it time to move on? SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Cephalothin; Antibiotics; Susceptibility; MIC; Urinary tract infection ID ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; CEPHALEXIN; CEFADROXIL; CEFPODOXIME; MECHANISMS; CEFAZOLIN; CEFACLOR AB Based on current epidemiologic and resistance trends, we propose reconsideration of the use of cephalothin susceptibility to predict susceptibility to oral narrow-spectrum cephalosporins among Enterobacteriaceae, particularly in predicting cephalexin susceptibility for urinary tract isolates. (c) 2013 Elsevier Inc. All rights reserved. C1 [Nguyen, Hien M.] Dept Infect Dis, Portland, OR USA. [Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA 90095 USA. RP Nguyen, HM (reprint author), Dept Infect Dis, Portland, OR USA. EM hien.m.nguyen@kp.org NR 18 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD AUG PY 2013 VL 76 IS 4 BP 483 EP 485 DI 10.1016/j.diagmicrobio.2013.03.022 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 195FK UT WOS:000322687500015 PM 23680238 ER PT J AU Sutfin, EL McCoy, TP Morrell, HER Hoeppner, BB Wolfson, M AF Sutfin, Erin L. McCoy, Thomas P. Morrell, Holly E. R. Hoeppner, Bettina B. Wolfson, Mark TI Electronic cigarette use by college students SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Electronic cigarettes; Young adults; College students; Nicotine; Smoking; Tobacco; Cigarettes ID SENSATION SEEKING; NICOTINE DELIVERY; NONRESPONSE BIAS; YOUNG-ADULTS; ALCOHOL-USE; TOBACCO USE; SMOKING; TRAJECTORIES; ADOLESCENCE; PREVALENCE AB Background: Electronic cigarettes, or e-cigarettes, are battery operated devices that deliver nicotine via inhaled vapor. There is considerable controversy about the disease risk and toxicity of e-cigarettes and empirical evidence on short- and long-term health effects is minimal. Limited data on e-cigarette use and correlates exist, and to our knowledge, no prevalence rates among U.S. college students have been reported. This study aimed to estimate the prevalence of e-cigarette use and identify correlates of use among a large, multi-institution, random sample of college students. Methods: 4444 students from 8 colleges in North Carolina completed a Web-based survey in fall 2009. Results: Ever use of e-cigarettes was reported by 4.9% of students, with 1.5% reporting past month use. Correlates of ever use included male gender, Hispanic or "Other race" (compared to non-Hispanic Whites), Greek affiliation, conventional cigarette smoking and e-cigarette harm perceptions. Although e-cigarette use was more common among conventional cigarette smokers, 12% of ever e-cigarette users had never smoked a conventional cigarette. Among current cigarette smokers, e-cigarette use was negatively associated with lack of knowledge about e-cigarette harm, but was not associated with intentions to quit. Conclusions: Although e-cigarette use was more common among conventional cigarette smokers, it was not exclusive to them. E-cigarette use was not associated with intentions to quit smoking among a sub-sample of conventional cigarette smokers. Unlike older, more established cigarette smokers, e-cigarette use by college students does not appear to be motivated by the desire to quit cigarette smoking. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Sutfin, Erin L.; Wolfson, Mark] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27157 USA. [McCoy, Thomas P.] Univ N Carolina, Ctr Hlth Vulnerable Populat, Sch Nursing, Greensboro, NC 27402 USA. [McCoy, Thomas P.] Univ N Carolina, Dept Educ Res Methodol, Greensboro, NC 27402 USA. [Morrell, Holly E. R.] Loma Linda Univ, Dept Psychol, Loma Linda, CA 92350 USA. [Hoeppner, Bettina B.] Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02114 USA. [Hoeppner, Bettina B.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. RP Sutfin, EL (reprint author), Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM ESutfin@wakehealth.edu FU National Institutes of Health [R01AA14007, F32CA141933, K01DA027097] FX This work was supported by grants from the National Institutes of Health (Grant Number R01AA14007 to Dr. Wolfson, Grant Number F32CA141933 to Dr. Morrell, and Grant Number K01DA027097 to Dr. Hoeppner). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Alcohol Abuse and Alcoholism or the National Institutes of Health. NR 54 TC 102 Z9 102 U1 2 U2 77 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2013 VL 131 IS 3 BP 214 EP 221 DI 10.1016/j.drugalcdep.2013.05.001 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 197MP UT WOS:000322855600005 PM 23746429 ER PT J AU Saxon, AJ AF Saxon, Andrew J. TI Donald A. Calsyn, Ph.D.: 1949-2013 SO DRUG AND ALCOHOL DEPENDENCE LA English DT Biographical-Item C1 VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Saxon, Andrew J.] Univ Washington, Seattle, WA 98195 USA. RP Saxon, AJ (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. EM Andrew.Saxon@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2013 VL 131 IS 3 BP 324 EP 324 DI 10.1016/j.drugalcdep.2013.04.011 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 197MP UT WOS:000322855600020 ER PT J AU Lindquist, KA Gendron, M Oosterwijk, S Barrett, LF AF Lindquist, Kristen A. Gendron, Maria Oosterwijk, Suzanne Barrett, Lisa Feldman TI Do People Essentialize Emotions? Individual Differences in Emotion Essentialism and Emotional Experience SO EMOTION LA English DT Article DE psychological essentialism; emotional complexity; beliefs ID BASIC EMOTIONS; PSYCHOLOGICAL CONSTRUCTION; SELF-REPORTS; PERCEPTION; CATEGORIES; LANGUAGE; BELIEFS; BRAIN; DIFFERENTIATION; DIMENSIONS AB Many scientific models of emotion assume that emotion categories are natural kinds that carve nature at its joints. These beliefs remain strong, despite the fact that the empirical record on the issue has remained equivocal for over a century. In this research, the authors examined one reason for this situation: People essentialize emotion categories by assuming that members of the same category (e.g., fear) have a shared metaphysical essence (i.e., a common causal mechanism). In Study 1, the authors found that lay people essentialize emotions by assuming that instances of the same emotion category have a shared essence that defines them, even when their surface features differ. Study 2 extended these findings, demonstrating that lay people tend to essentialize categories the more a category is of the body (vs. the mind). In Study 3, we examined the links between emotion essentialism and the complexity of actual emotional experiences. In particular, we predicted and found that individuals who hold essentialist beliefs about emotions describe themselves as experiencing highly differentiated emotional experiences but do not show evidence of stronger emotional differentiation in their momentary ratings of experience in everyday life. Implications for the science of emotion are discussed. C1 [Lindquist, Kristen A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Gendron, Maria] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Gendron, Maria; Oosterwijk, Suzanne; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA USA. [Oosterwijk, Suzanne] Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Lindquist, KA (reprint author), Univ N Carolina, Dept Psychol, Davie Hall 321, Chapel Hill, NC 27599 USA. EM kristen.lindquist@unc.edu NR 81 TC 1 Z9 1 U1 4 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD AUG PY 2013 VL 13 IS 4 BP 629 EP 644 DI 10.1037/a0032283 PG 16 WC Psychology, Experimental SC Psychology GA 195FM UT WOS:000322687700006 PM 23668818 ER PT J AU Gaspard, N Foreman, B Judd, LM Brenton, JN Nathan, BR McCoy, BM Al-Otaibi, A Kilbride, R Fernandez, IS Mendoza, L Samuel, S Zakaria, A Kalamangalam, GP Legros, B Szaflarski, JP Loddenkemper, T Hahn, CD Goodkin, HP Claassen, J Hirsch, LJ LaRoche, SM AF Gaspard, Nicolas Foreman, Brandon Judd, Lilith M. Brenton, James N. Nathan, Barnett R. McCoy, Blathnaid M. Al-Otaibi, Ali Kilbride, Ronan Fernandez, Ivan Sanchez Mendoza, Lucy Samuel, Sophie Zakaria, Asma Kalamangalam, Giridhar P. Legros, Benjamin Szaflarski, Jerzy P. Loddenkemper, Tobias Hahn, Cecil D. Goodkin, Howard P. Claassen, Jan Hirsch, Lawrence J. LaRoche, Suzette M. CA Critical Care EEG Monitoring Res TI Intravenous ketamine for the treatment of refractory status epilepticus: A retrospective multicenter study SO EPILEPSIA LA English DT Article DE Ketamine; Treatment; Refractory status epilepticus; Anesthetics; Antiepileptic drugs ID NEUROTOXICITY; ISOFLURANE; MIDAZOLAM; ACIDOSIS; IMPACT AB Purpose To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). Methods Multicenter retrospective review of medical records and electroencephalography (EEG) reports in 10 academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE that were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. Key Findings Permanent control of RSE was achieved in 57% (34 of 60) of episodes. Ketamine was felt to have contributed to permanent control (possible or likely responses) in 32% (19 of 60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with postanoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9mg/kg/h, when ketamine was introduced at least 8days after SE onset, or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26 of 60), but was lower when SE was controlled within 24h of ketamine initiation (16% vs. 56%, p=0.0047). Significance Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE. C1 [Gaspard, Nicolas; Hirsch, Lawrence J.] Yale Univ, Yale New Haven Hosp, Sch Med, Comprehens Epilepsy Ctr,Dept Neurol, New Haven, CT 06520 USA. [Foreman, Brandon; Claassen, Jan] Columbia Univ Coll Phys & Surg, Div Crit Care Neurol, New York, NY 10032 USA. [Foreman, Brandon; Claassen, Jan] Med Ctr, New York, NY USA. [Judd, Lilith M.; LaRoche, Suzette M.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Brenton, James N.; Nathan, Barnett R.; Goodkin, Howard P.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [McCoy, Blathnaid M.; Al-Otaibi, Ali; Hahn, Cecil D.] Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada. [Kilbride, Ronan] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA. [Kilbride, Ronan] Massachusetts Gen Hosp, Dept Neurol, Clin Neurophysiol Serv, Boston, MA 02114 USA. [Fernandez, Ivan Sanchez; Loddenkemper, Tobias] Boston Childrens Hosp, Div Epilepsy & Clin Neurophysiol, Boston, MA USA. [Mendoza, Lucy; Szaflarski, Jerzy P.] Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, Cincinnati, OH USA. [Samuel, Sophie; Zakaria, Asma; Kalamangalam, Giridhar P.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA. [Legros, Benjamin] ULB Hop Erasme, Dept Neurol, Reference Ctr Treatment Refractory Epilepsy, Brussels, Belgium. RP Gaspard, N (reprint author), Yale Univ, Comprehens Epilepsy Ctr, 15 York St,LLCI 714, New Haven, CT 06520 USA. EM nicolas.gaspard@yale.edu RI Hahn, Cecil/J-3372-2016; OI Hahn, Cecil/0000-0002-0887-8761; Loddenkemper, Tobias/0000-0003-2074-0674; Brenton, James/0000-0001-9432-1347 FU Belgian American Education Foundation; Commission for Educational Exchange between the United States and Belgium; Belgian Neurological Society; Pfizer's Medical and Academic Partnerships Program; Fundacion Alfonso Martin Escudero; UCB Pharma; American Academy of Neurology; David-Phinney Foundation/Sunflower Revolution; NIH/NINDS; University of Cincinnati Research Council; National Institutes of Health/NINDS; Harvard Medical School; Boston Children's Hospital; Program for Quality and Safety at Boston Children's Hospital; Payer Provider Quality Initiative; Epilepsy Foundation of America; Center for Integration of Medicine and Innovative Technology; Epilepsy Therapy Project; American Epilepsy Society; Cure; Lundbeck; Eisai; Canadian Institutes of Health Research; PSI Foundation; SickKids Foundation; UCB-Pharma; Upsher-Smith; GlaxoSmithKline; National Institutes of Health/SBIR FX N.G. was the recipient of a Postdoctoral Research Fellowship from the Belgian American Education Foundation, and received research grant from the Commission for Educational Exchange between the United States and Belgium and the Belgian Neurological Society. B. F. received funding from Pfizer's Medical and Academic Partnerships Program.; I.S.F. was funded by a grant for the study of Epileptic Encephalopathies from 'Fundacion Alfonso Martin Escudero.' B. L. has received funding for research from UCB Pharma; serves on the advisory board of UCB Pharma, GlaxoSmithKline (GSK), and Pfizer; and received speaker honoraria from UCB Pharma and GSK. J.P.S. has served on an advisory board for UCB Pharma. He serves on the editorial board of Epilepsy and Behavior, Epileptologia, and Restorative Neurology and Neuroscience. He has received honoraria from American Epilepsy Society and UCB Pharma, and he is on speakers' bureaus for UCB Pharma. He has received funding for research from the American Academy of Neurology, David-Phinney Foundation/Sunflower Revolution, UCB Pharma, NIH/NINDS, and the University of Cincinnati Research Council. He has served as an expert witness in legal proceedings for the government.; T.L. serves on the Laboratory Accreditation Board for Long Term (Epilepsy and Intensive Care Unit) Monitoring, on the Council of the American Clinical Neurophysiology Society, on the American Board of Clinical Neurophysiology, as an Associate Editor for Seizure, and performs video-electroencephalography long-term monitoring, electroencephalography, and other electrophysiologic studies at Boston Children's Hospital and bills for these procedures. T. L. receives research support from the National Institutes of Health/NINDS, a Career Development Fellowship Award from Harvard Medical School and Boston Children's Hospital, the Program for Quality and Safety at Boston Children's Hospital, the Payer Provider Quality Initiative, The Epilepsy Foundation of America, the Center for Integration of Medicine and Innovative Technology, the Epilepsy Therapy Project, the American Epilepsy Society, Cure, and from investigator initiated research grants from Lundbeck and Eisai.; C.D.H. is supported by research grants from the Canadian Institutes of Health Research, PSI Foundation and SickKids Foundation. L.J.H. has received research support for investigator-initiated studies from UCB-Pharma, Upsher-Smith, and Lundbeck; consultation fees for advising from Lundbeck, Upsher-Smith, UCB-Pharma, and GlaxoSmithKline; and royalties for authoring chapters for UpToDate-Neurology, and for co-authoring the book "Atlas of EEG in Critical Care," by Hirsch and Brenner (2010). S. M. L. has received research support from the National Institutes of Health/SBIR, and for investigator-initiated studies from UCB Pharma. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 27 TC 49 Z9 53 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2013 VL 54 IS 8 BP 1498 EP 1503 DI 10.1111/epi.12247 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 199KA UT WOS:000322992200024 PM 23758557 ER PT J AU Zhou, T Hasty, P Walter, CA Bishop, AJR Scott, LM Rebel, VI AF Zhou, Ting Hasty, Paul Walter, Christi A. Bishop, Alexander J. R. Scott, Linda M. Rebel, Vivienne I. TI Myelodysplastic syndrome: An inability to appropriately respond to damaged DNA? SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID HEMATOPOIETIC STEM-CELLS; BASE EXCISION-REPAIR; ROTHMUND-THOMSON SYNDROME; FLUDARABINE COMBINATION CHEMOTHERAPY; BONE-MARROW FAILURE; FANCONI-ANEMIA; MYELOID-LEUKEMIA; MISMATCH REPAIR; MOUSE MODEL; CHROMOSOMAL INSTABILITY AB Myelodysplastic syndrome (MDS) is considered a hematopoietic stem cell disease that is characterized by abnormal hematopoietic differentiation and a high propensity to develop acute myeloid leukemia. It is mostly associated with advanced age, but also with prior cancer therapy and inherited syndromes related to abnormalities in DNA repair. Recent technologic advances have led to the identification of a myriad of frequently occurring genomic perturbations associated with MDS. These observations suggest that MDS and its progression to acute myeloid leukemia is a genomic instability disorder, resulting from a stepwise accumulation of genetic abnormalities. The notion is now emerging that the underlying mechanism of this disease could be a defect in one or more pathways that are involved in responding to or repairing damaged DNA. In this review, we discuss these pathways in relationship to a large number of studies performed with MDS patient samples and MDS mouse models. Moreover, in view of our current understanding of how DNA damage response and repair pathways are affected by age in hematopoietic stem cells, we also explore how this might relate to MDS development. (c) 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Zhou, Ting; Bishop, Alexander J. R.; Rebel, Vivienne I.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Zhou, Ting; Walter, Christi A.; Bishop, Alexander J. R.; Rebel, Vivienne I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Hasty, Paul] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Hasty, Paul; Walter, Christi A.; Bishop, Alexander J. R.; Rebel, Vivienne I.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy Res Ctr, San Antonio, TX 78229 USA. [Hasty, Paul; Walter, Christi A.; Bishop, Alexander J. R.; Rebel, Vivienne I.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Walter, Christi A.] South Texas Vet Hlth Care Syst, Audie Murphy Hosp, San Antonio, TX USA. [Scott, Linda M.] Univ Queensland, Fac Hlth Sci, Diamantina Inst, Brisbane, Qld, Australia. [Scott, Linda M.] Univ Queensland, Fac Hlth Sci, Sch Med, Brisbane, Qld, Australia. RP Rebel, VI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM rebel@uthscsa.edu RI Scott, Linda/D-9777-2012 OI Scott, Linda/0000-0003-0334-1479 FU National Institute of Aging [5R21AG033339]; National Institute of Environmental Health Sciences [1RO1ES022054]; Hyundai Hope on Wheels FX This work was supported by the National Institute of Aging (grant 5R21AG033339 to V.I.R. and C.A.W.), the National Institute of Environmental Health Sciences (grant 1RO1ES022054 to P.E.H. and V.I.R.), and Hyundai Hope on Wheels (to A.J.R.B. and V.I.R.). NR 108 TC 13 Z9 13 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2013 VL 41 IS 8 BP 665 EP 674 DI 10.1016/j.exphem.2013.04.008 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 199VX UT WOS:000323024700001 PM 23643835 ER PT J AU Lynch, JA Khoury, MJ Borzecki, A Cromwell, J Hayman, LL Ponte, PR Miller, GA Lathan, CS AF Lynch, Julie A. Khoury, Muin J. Borzecki, Ann Cromwell, Jerry Hayman, Laura L. Ponte, Pat Reid Miller, Glenn A. Lathan, Christopher S. TI Utilization of epidermal growth factor receptor (EGFR) testing in the United States: a case study of T3 translational research SO GENETICS IN MEDICINE LA English DT Article DE dissemination and implementation; EGFR assay; equity in access; lung cancer genomics; T3 translation ID CELL LUNG-CANCER; AFRICAN-AMERICANS; MUTATIONS; GEFITINIB; GENOMICS; FREQUENCY; MEDICINE; SURGERY; RISK; CARE AB Purpose: We examined hospital use of the epidermal growth factor receptor assay in patients with lung cancer in the United States. Our goal was to inform the development of a model to predict phase 3 translation of guideline-directed molecular diagnostic tests. Methods: This was a retrospective observational study. Using logistic regression, we analyzed the association between hospitals' institutional and regional characteristics and the likelihood that an epidermal growth factor receptor assay would be ordered. Results: Significant institutional predictors included affiliation with an academic medical center (odds ratio, 1.48; 95% confidence interval, 1.20-1.83), participation in a National Cancer Institute clinical research cooperative group (odds ratio, 2.06, 1.66-2.55), and availability of positron emission tomography scan (odds ratio, 1.44, 1.07-1.94) and cardiothoracic surgery (odds ratio, 1.90, 1.52-2.37) services. Significant regional predictors included metropolitan county (odds ratio, 2.08, 1.48-2.91), population with above-average education (odds ratio, 1.46, 1.09-1.96), and population with above-average income (odds ratio, 1.46, 1.04-2.05). Distance from a National Cancer Institute cancer center was a negative predictor (odds ratio, 0.996, 0.995-0.998), with a 34% decrease in likelihood for every 100 miles. Conclusion: In 2010, only 12% of US acute-care hospitals ordered the epidermal growth factor receptor assay, suggesting that most patients with lung cancer did not have access to this test. This case study illustrated the need for: (i) increased dissemination and implementation research, and (ii) interventions to improve adoption of guideline-directed molecular diagnostic tests by community hospitals. C1 [Lynch, Julie A.] Univ Massachusetts, Vet Hlth Adm, Boston, MA 02125 USA. [Lynch, Julie A.; Ponte, Pat Reid; Lathan, Christopher S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Khoury, Muin J.] NCI, Off Publ Hlth Genom, CDC, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA. [Lynch, Julie A.; Borzecki, Ann] Vet Hlth Adm, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Cromwell, Jerry; Hayman, Laura L.] Univ Massachusetts, Boston, MA 02125 USA. [Cromwell, Jerry] Res Triangle Inst, Boston, MA USA. [Miller, Glenn A.] Genzyme Genet, Santa Fe, NM USA. RP Lynch, JA (reprint author), Univ Massachusetts, Vet Hlth Adm, Harbor Campusol, Boston, MA 02125 USA. EM Julie.Lynch@va.gov FU Center for Health Quality, Outcomes and Economic Research, a Veterans Administration Health Services Research and Development Center of Excellence; Department of Education GAANN [P200A060243]; National Institute of Health [DFCI/UMB U54 CA156734-01]; Susan G. Komen Foundation; Lynch Foundation FX J.A.L. has received funding from the Center for Health Quality, Outcomes and Economic Research, a Veterans Administration Health Services Research and Development Center of Excellence; Department of Education GAANN #P200A060243; National Institute of Health DFCI/UMB U54 CA156734-01, Susan G. Komen Foundation, and the Lynch Foundation. Methodology and preliminary results were previously presented as a poster at the 10th International Congress on Targeted Anticancer Therapies, Amsterdam, 8-10 March 2012 NR 39 TC 13 Z9 13 U1 0 U2 3 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 AUG PY 2013 VL 15 IS 8 BP 630 EP 638 DI 10.1038/gim.2013.5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 195NM UT WOS:000322709800006 PM 23448725 ER PT J AU Maesta, I Growdon, WB Goldstein, DP Bernstein, MR Horowitz, NS Rudge, MVC Berkowitz, RS AF Maesta, Izildinha Growdon, Whitfield B. Goldstein, Donald P. Bernstein, Marilyn R. Horowitz, Neil S. Cunha Rudge, Marilza Vieira Berkowitz, Ross S. TI Prognostic factors associated with time to hCG remission in patients with low-risk postmolar gestational trophoblastic neoplasia SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Low-risk gestational trophoblastic neoplasia; hCG remission; Prognostic factors; Chemotherapy ID WEEKLY INTRAMUSCULAR METHOTREXATE; FOLINIC ACID; RETROSPECTIVE COHORT; TREATMENT OUTCOMES; MOLAR PREGNANCY; PRIMARY THERAPY; ACTINOMYCIN-D; DISEASE; MANAGEMENT; CHEMOTHERAPY AB Objective. The purpose of this study was to identify the clinical factors associated with time to hCG remission among women with low-risk postmolar GTN. Methods. This study included a non-concurrent cohort of 328 patients diagnosed with low-risk postmolar GTN according to FIGO 2002 criteria. Associations of time to hCG remission with history of prior mole, molar histology, time to persistence, use of D&C at persistence, presence of metastatic disease, FIGO score, hCG values at persistence, type of first line therapy and use of multiagent chemotherapy were investigated with both univariate and multivariate analyses. Results. Overall median time to remission was 46 days. Ten percent of the patients required multi-agent chemotherapy to achieve hCG remission. Multivariate analysis incorporating the variables significant on univariate analysis confirmed that complete molar histology (HR 1.45), metastatic disease (HR 1.66), use of multi-agent therapy (HR 2.00) and FIGO score (HR 1.82) were associated with longer time to remission. There was a linear relationship between FIGO score and time to hCG remission. Each 1-point increment in FIGO score was associated with an average 17-day increase in hCG remission time (95% CI: 12.5-21.6). Conclusions. Complete mole histology prior to GTN, presence of metastatic disease, use of multi-agent therapy and higher FIGO score were independent factors associated with longer time to hCG remission in low-risk GTN. Identifying the prognostic factors associated with time to remission and effective counseling may help improve treatment planning and reduce anxiety in patients and their families. (C) 2013 Elsevier Inc. All rights reserved. C1 [Maesta, Izildinha; Cunha Rudge, Marilza Vieira] Sao Paulo State Univ, UNESP, Botucatu Med Sch, Dept Gynecol & Obstet, Botucatu, SP, Brazil. [Growdon, Whitfield B.] Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynaecol, Boston, MA 02114 USA. [Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynaecol, Boston, MA 02115 USA. [Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Donald P Goldstein MD Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. [Maesta, Izildinha; Cunha Rudge, Marilza Vieira] Sao Paulo State Univ, UNESP, Trophoblast Dis Ctr, Botucatu Med Sch, Botucatu, SP, Brazil. [Growdon, Whitfield B.; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. [Growdon, Whitfield B.; Goldstein, Donald P.; Bernstein, Marilyn R.; Horowitz, Neil S.; Berkowitz, Ross S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), ASBI, Brigham & Womens Hosp, Dept OBGYN, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org RI Rudge, Marilza /C-8338-2012 OI Rudge, Marilza /0000-0002-9227-832X NR 33 TC 4 Z9 5 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2013 VL 130 IS 2 BP 312 EP 316 DI 10.1016/j.ygyno.2013.05.017 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 191KD UT WOS:000322410900012 PM 23707672 ER PT J AU Hanna, J Reimann, JDR Haddad, RI Krane, JF AF Hanna, John Reimann, Julie D. R. Haddad, Robert I. Krane, Jeffrey F. TI Human papillomavirus-associated adenocarcinoma of the base of the tongue SO HUMAN PATHOLOGY LA English DT Article DE Human papillomavirus; Adenocarcinoma; Oropharynx; p16 ID SQUAMOUS-CELL CARCINOMA; OROPHARYNX; HEAD; CANCER; ENTITY AB Human papillomavirus (HPV) is a major cause of oropharyngeal squamous cell carcinoma with characteristic clinical and pathologic features relative to their non-HPV-associated counterparts. Here we describe 2 cases of HPV-associated adenocarcinoma of the oropharynx. Both cases arose at the base of the tongue, and neither had the histologic or immunohistochemical features of a primary salivary gland tumor or metastasis from another location. One patient had metastases to neck lymph nodes and the lungs and died of disease 37 months after diagnosis. Evidence for an HPV association consisted of strong diffuse expression of p16, polyrnerase chain reaction-based detection of HPV16 DNA sequences, and localization of HPV by in situ hybridization within tumor cells of both primary and metastatic lesions. These results further expand the spectrum of HPV-associated head and neck malignancy. This rare entity should be distinguished from primary salivary gland adenocarcinoma and may be a candidate for HPV-specific targeted therapies. (C) 2013 Elsevier Inc. All rights reserved. C1 [Hanna, John; Reimann, Julie D. R.; Krane, Jeffrey F.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Haddad, Robert I.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Haddad, Robert I.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krane, JF (reprint author), Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. EM jkrane@partners.org NR 12 TC 4 Z9 4 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD AUG PY 2013 VL 44 IS 8 BP 1516 EP 1523 DI 10.1016/j.humpath.2012.12.004 PG 8 WC Pathology SC Pathology GA 191KX UT WOS:000322413000009 PM 23465278 ER PT J AU Stirman, SW Shields, N Deloriea, J Landy, MSH Belus, JM Maslej, MM Monson, CM AF Stirman, Shannon Wiltsey Shields, Norman Deloriea, Josh Landy, Meredith S. H. Belus, Jennifer M. Maslej, Marta M. Monson, Candice M. TI A randomized controlled dismantling trial of post-workshop consultation strategies to increase effectiveness and fidelity to an evidence-based psychotherapy for Posttraumatic stress disorder SO IMPLEMENTATION SCIENCE LA English DT Article DE Training; Implementation; Consultation; Psychotherapy; PTSD; Cognitive processing therapy ID COGNITIVE-PROCESSING THERAPY; NATIONAL COMORBIDITY SURVEY; MENTAL-HEALTH-SERVICES; VIETNAM VETERANS; PSYCHOLOGICAL TREATMENTS; PSYCHOMETRIC PROPERTIES; BEHAVIOR PROBLEMS; PERCEIVED HEALTH; DISSEMINATION; DEPRESSION AB Background: Posttraumatic Stress Disorder (PTSD) is a serious mental health condition with substantial costs to individuals and society. Among military veterans, the lifetime prevalence of PTSD has been estimated to be as high as 20%. Numerous research studies have demonstrated that short-term cognitive-behavioral psychotherapies, such as Cognitive Processing Therapy (CPT), lead to substantial and sustained improvements in PTSD symptoms. Despite known benefits, only a minority of clinicians provide these therapies. Transferring this research knowledge into clinical settings remains one of the largest hurdles to improving the health of veterans with PTSD. Attending a workshop alone is insufficient to promote adequate knowledge transfer and sustained skill; however, relatively little research has been conducted to identify effective post-training support strategies. Methods: The current study investigates whether clinicians receiving post-workshop support (six-month duration) will deliver CPT with greater fidelity (i.e., psychotherapy adherence and competence) and have improved patient outcomes compared with clinicians receiving no formal post-workshop support. The study conditions are: technology-enhanced group tele-consultation; standard group tele-consultation; and fidelity assessment with no consultation. The primary outcome is independent assessment (via audio-recordings) of the clinicians' adherence and competence in delivering CPT. The secondary outcome is observed changes in patient symptoms during and following treatment as a function of clinician fidelity. Post-consultation interviews with clinicians will help identify facilitators and barriers to psychotherapy skill acquisition. The study results will inform how best to implement and transfer evidence-based psychotherapy (e. g., CPT) to clinical settings to attain comparable outcomes to those observed in research settings. Discussion: Findings will deepen our understanding of how much and what type of support is needed following a workshop to help clinicians become proficient in delivering a new protocol. Several influences on clinician learning and patient outcomes will be discussed. An evidence-based model of clinical consultation will be developed, with the ultimate goal of informing policy and influencing best practice in clinical consultation. C1 [Stirman, Shannon Wiltsey] Boston Univ, VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Shields, Norman] Vet Affairs Canada, OSINN, Ste Anne De Bellevue, PQ H9X 1Y9, Canada. [Deloriea, Josh; Landy, Meredith S. H.; Maslej, Marta M.; Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON M5B 2K3, Canada. [Belus, Jennifer M.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. RP Monson, CM (reprint author), Ryerson Univ, Dept Psychol, 350 Victoria St, Toronto, ON M5B 2K3, Canada. EM candice.monson@psych.ryerson.ca OI Wiltsey Stirman, Shannon/0000-0001-9917-5078 NR 71 TC 2 Z9 2 U1 3 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD AUG 1 PY 2013 VL 8 AR 82 DI 10.1186/1748-5908-8-82 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 198ZW UT WOS:000322964300001 ER PT J AU Psaltis, AJ Schlosser, RJ Yawn, JR Henriquez, O Mulligan, JK AF Psaltis, Alkis J. Schlosser, Rodney J. Yawn, James R. Henriquez, Oswaldo Mulligan, Jennifer K. TI Characterization of B-cell subpopulations in patients with chronic rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE Chronic rhino sinusitis; B lymphocytes; B cells; plasma cells; Nasal polyps; chronic inflammation; sinusitis ID NASAL POLYPS AB Background: Recent research suggest that B and plasma cells may play an important role in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this study was to subcharacterize the B cell response in the sinus mucosa of control and CRS patients. Methods: Representative tissue samples and peripheral blood samples were obtained from controls, CRS without nasal polyps (CRSsNP) and CRSwNP. Using single-cell suspension flow cytometry these samples were analyzed for overall and stage-specific B and plasma cell percentages. Results: Both atopic and nonatopic CRSwNP patients showed an increase in local numbers of naive, active, and memory B cells compared to controls. CRSsNP patients only showed local elevations of naive B cells. Plasma cells were only significantly elevated in the sinus tissue of atopic CRSwNP patients. These local tissue increases did not correlate with increased numbers of circulating B cells. Conclusion: This study provides further evidence of an important role of B cells in CRSwNP patients. The local increase appears to be independent of a systemic response. (C) 2013 ARS-AAOA, LLC. C1 [Psaltis, Alkis J.; Schlosser, Rodney J.; Yawn, James R.; Henriquez, Oswaldo; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.; Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Psaltis, AJ (reprint author), Stanford Univ, Stanford Sch Med, Dept Otolaryngol Head & Neck Surg, 801 Welch Rd, Palo Alto, CA 94303 USA. EM alkispsaltis@gmail.com FU American Academy of Otolaryngic Allergy; Garnett Passe and Rodney Williams Memorial Foundation; Department of Veterans Affairs; Flight Attendant Medical Research Institutes FX Funding sources for the study: American Academy of Otolaryngic Allergy (to A.J.P.); Garnett Passe and Rodney Williams Memorial Foundation (to A.J.P.); Department of Veterans Affairs (to R.J.S.); Flight Attendant Medical Research Institutes (to J.K.M. and R.J.S.). NR 23 TC 9 Z9 9 U1 1 U2 6 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 AUG PY 2013 VL 3 IS 8 BP 621 EP 629 DI 10.1002/alr.21173 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 201WE UT WOS:000323172900004 PM 23640795 ER PT J AU Feldman, RE Lam, AC Sadow, PM Bleier, BS AF Feldman, Rachel E. Lam, Allen C. Sadow, Peter M. Bleier, Benjamin S. TI P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic sinusitis; nasal polyposis; P-glycoprotein; active efflux pumps; inflammation; Th1; Th2; eosinophilia; eosinophilic chronic rhinosinusitis; Lund-Mackay score ID EPITHELIAL-CELLS AB Background: P-glycoprotein (P-gp) is a membrane-bound efflux pump that is upregulated in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and participates in epithelial cytokine secretion. Eosinophilic CRS (ECRS) shares a similar cytokine profile with CRSwNP and is associated with significant inflammation and poor surgical outcomes. The goal of this study is to determine if P-gp expression is associated with degree of eosinophilia and severity of radiographic inflammation in patients with CRS without polyps (CRSsNP). Methods: An institutional review board (IRB)-approved study using sinus tissue in 39 steroid-naive patients with CRS. P-gp expression was calculated using quantitative fluorescent immunohistochemistry (Q-FIHC) to generate an epithelial to background staining ratio. Patients were stratified into low and high epithelial expression groups (<3 and >= 3, respectively). Average eosinophils per high powered field (hpf) and Lund-Mackay scores were calculated and compared with P-gp staining ratios using a 2-tailed Student t test. Results: Among the 39 patients, 7 (17.95%) had high P-gp expression ratios (mean +/- SD, 4.86 +/- 1.33) while 32 (82.05%) had low expression ratios (1.91 +/- 0.45). The number of eosinophils/hpf were significantly greater in the high P-gp expression group as compared to the low expression group (62.38 +/- 83.69 vs 5.11 +/- 10.12, p = 0.0003). The Lund-Mackay scores were significantly greater in the high P-gp expression group as compared to the low expression group (11.86 +/- 2.79 vs 6.84 +/- 4.19, p = 0.005). Conclusion: P-gp is known to be overexpressed in CRSwNP. This study suggests that among patients with CRSsNP, P-gp is similarly overexpressed in those with high tissue eosinophilia and correlates with severity of radiographic inflammation. (C) 2013 The Authors. International Forum of Allergy & Rhinology, published by Wiley Periodicals, Inc., on behalf of ARS-AAOA, LLC. C1 [Feldman, Rachel E.; Lam, Allen C.; Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Sadow, Peter M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM bleierb@gmail.com NR 15 TC 12 Z9 13 U1 0 U2 1 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 AUG PY 2013 VL 3 IS 8 BP 684 EP 687 DI 10.1002/alr.21176 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 201WE UT WOS:000323172900014 PM 23677641 ER PT J AU Lochhead, P Kuchiba, A Imamura, Y Liao, XY Yamauchi, M Nishihara, R Qian, ZR Morikawa, T Shen, JN Meyerhardt, JA Fuchs, CS Ogino, S AF Lochhead, Paul Kuchiba, Aya Imamura, Yu Liao, Xiaoyun Yamauchi, Mai Nishihara, Reiko Qian, Zhi Rong Morikawa, Teppei Shen, Jeanne Meyerhardt, Jeffrey A. Fuchs, Charles S. Ogino, Shuji TI Microsatellite Instability and BRAF Mutation Testing in Colorectal Cancer Prognostication SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; III COLON-CANCER; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; DEFECTIVE MISMATCH REPAIR; FATTY-ACID SYNTHASE; BODY-MASS INDEX; STAGE-II; ADJUVANT THERAPY; KRAS MUTATION; PERSONALIZED MEDICINE AB BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAFwild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAFwild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60 (95% confidence interval [CI] 1.12 to 2.28; P .009), 0.48 (95% CI 0.27 to 0.87; P .02), and 0.25 (95% CI 0.12 to 0.52; P < .001), respectively. No evidence existed for a differential prognostic role of BRAF mutation by MSI status (P-interaction > .50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification. C1 [Lochhead, Paul; Kuchiba, Aya; Imamura, Yu; Liao, Xiaoyun; Yamauchi, Mai; Nishihara, Reiko; Qian, Zhi Rong; Morikawa, Teppei; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lochhead, Paul; Kuchiba, Aya; Imamura, Yu; Liao, Xiaoyun; Yamauchi, Mai; Nishihara, Reiko; Qian, Zhi Rong; Morikawa, Teppei; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland. [Shen, Jeanne; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Rm M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu OI Qian, Zhi rong/0000-0003-1633-4120 FU US National Institutes of Health [P01 CA87969, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA151993]; Bennett Family Fund; Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance; Frank Knox Memorial Fellowship at Harvard University; Chief Scientist Office of the Scottish Government; Japan Society for Promotion of Science FX This work was supported by the US National Institutes of Health (P01 CA87969 to S. E. Hankinson; P01 CA55075 and UM1 CA167552 to W. C. Willett; P50 CA127003 to CSF; and R01 CA151993 to SO); by the Bennett Family Fund and the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance; by the Frank Knox Memorial Fellowship at Harvard University (to PL); by a fellowship from the Chief Scientist Office of the Scottish Government (to PL); and by a fellowship from the Japan Society for Promotion of Science (to TM). NR 79 TC 133 Z9 133 U1 1 U2 25 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 AUG PY 2013 VL 105 IS 15 BP 1151 EP 1156 DI 10.1093/jnci/djt173 PG 6 WC Oncology SC Oncology GA 199DZ UT WOS:000322976000013 PM 23878352 ER PT J AU Bodenlos, JS Noonan, M Wells, SY AF Bodenlos, Jamie S. Noonan, Marleah Wells, Stephanie Y. TI Mindfulness and Alcohol Problems in College Students: The Mediating Effects of Stress SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE alcohol; college; mental health; mindfulness; stress ID SUBSTANCE USE DISORDERS; PERCEIVED STRESS; RELAPSE PREVENTION; ACADEMIC STRESS; REDUCTION MBSR; 1ST YEAR; MEDITATION; SYMPTOMS; DRINKING; DISTRESS AB Objective: To examine the relationship between mindfulness and alcohol problems in college students, as well as the role of stress as a mediator in this relationship. Participants: Participants were 310 students from a small, private college in the Northeast. Methods: Students completed self-report measures, including the Perceived Stress Scale, the Five Facet Mindfulness Questionnaire, and the Rutgers Alcohol Problems Index. Results: Mindfulness was negatively correlated with alcohol problems and stress, whereas stress positively correlated with alcohol problems. Results implicated stress as fully mediating the relationship between mindfulness and alcohol problems. Alcohol problems were negatively correlated with the Acting With Awareness and Describing Experience facets of mindfulness. Conclusion: Mindfulness-based stress reduction or other mindfulness programs may be useful in decreasing alcohol problems on college campuses via the effects on stress. C1 [Bodenlos, Jamie S.] Hobart & William Smith Coll, Dept Psychol, Geneva, NY 14456 USA. [Noonan, Marleah] Boston Coll, Counseling Dev & Educ Psychol Dept, Lynch Sch Educ, Boston, MA USA. [Wells, Stephanie Y.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. RP Bodenlos, JS (reprint author), Hobart & William Smith Coll, Dept Psychol, 217 Gulick Hall, Geneva, NY 14456 USA. EM bodenlos@hws.edu NR 62 TC 9 Z9 10 U1 4 U2 52 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD AUG 1 PY 2013 VL 61 IS 6 BP 371 EP 378 DI 10.1080/07448481.2013.805714 PG 8 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 197PR UT WOS:000322863600006 PM 23930751 ER PT J AU Jibodh, SR Schwarzkopf, R Anthony, SG Malchau, H Dempsey, KE Estok, DM AF Jibodh, Stefan R. Schwarzkopf, Ran Anthony, Shawn G. Malchau, Henrik Dempsey, Kyle E. Estok, Daniel M., II TI Revision Hip Arthroplasty with A Modular Cementless Stem: Mid-Term Follow Up SO JOURNAL OF ARTHROPLASTY LA English DT Article DE revision hip arthroplasty; modular femoral stems; cementless femoral stems; fully coated femoral stems ID EXTENDED TROCHANTERIC OSTEOTOMY; POROUS-COATED STEMS; PROXIMAL BONE LOSS; FEMORAL COMPONENT; UNITED-STATES; RADIOGRAPHIC ANALYSIS; KNEE ARTHROPLASTY; FIXATION; REPLACEMENT; DISLOCATION AB Despite the increasing volume of revision total hip arthroplasty (THA) being performed in the United States, there are few studies reporting mid-term clinical and radiographic outcomes of modular fully porous-coated femoral stems. We retrospectively studied a consecutive series of patients who underwent revision THA with a modular extensively porous-coated femoral component at a single institution and by a single surgeon. The final study group included 54 hips (52 patients) followed for an average of 84months. Ten-year survival rates with revision for any reason and revision for femoral loosening as endpoints were 94% and 100%, respectively. No complications regarding the modular junction were encountered. Of the 50 hips with adequate radiographs, all showed proximal ingrowth and 42 (84%) had both proximal and distal ingrowth. The modular, fully porous-coated femoral stem studied demonstrated excellent survivorship and bone ingrowth at mid-term follow up. (C) 2013 Elsevier Inc. All rights reserved. C1 [Jibodh, Stefan R.] Kaiser Permanente Walnut Creek, Dept Orthopaed Surg, Walnut Creek, CA USA. [Schwarzkopf, Ran; Dempsey, Kyle E.; Estok, Daniel M., II] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Anthony, Shawn G.; Malchau, Henrik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Harris Orthopaed Biomech & Bi, Boston, MA USA. RP Jibodh, SR (reprint author), 1425 South Main St, Walnut Creek, CA 94596 USA. OI Malchau, Henrik/0000-0002-4291-2441 NR 51 TC 9 Z9 10 U1 1 U2 3 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 AUG PY 2013 VL 28 IS 7 BP 1167 EP 1172 DI 10.1016/j.arth.2012.07.031 PG 6 WC Orthopedics SC Orthopedics GA 198LN UT WOS:000322924500023 PM 23114191 ER PT J AU CorveraTindel, T Doering, LV AF CorveraTindel, Teresita Doering, Lynn V. TI Social Connections and Depressive Symptoms in Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 17th Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA) CY SEP 22-25, 2013 CL Orlando, FL SP Heart Failure Soc Amer (HFSA) C1 [CorveraTindel, Teresita] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Doering, Lynn V.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2013 VL 19 IS 8 SU 1 MA 014 BP S6 EP S6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201LG UT WOS:000323142500015 ER PT J AU Kashyap, A Dezellem, S Vardeny, O AF Kashyap, Anita Dezellem, Sheryl Vardeny, Orly TI A Retrospective Evaluation of Spironolactone Versus Eplerenone on Potassium Homeostasis and Renal Function SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 17th Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA) CY SEP 22-25, 2013 CL Orlando, FL SP Heart Failure Soc Amer (HFSA) C1 [Kashyap, Anita; Dezellem, Sheryl] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Vardeny, Orly] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2013 VL 19 IS 8 SU 1 MA 077 BP S28 EP S28 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201LG UT WOS:000323142500077 ER PT J AU Niehaus, ED Malhotra, R Cocca-Spofford, D Lewis, GD AF Niehaus, Emily D. Malhotra, Rajeev Cocca-Spofford, Diane Lewis, Gregory D. TI Repletion of Iron Stores in Patients with Systolic Heart Failure Using Oral Iron Supplementation SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 17th Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA) CY SEP 22-25, 2013 CL Orlando, FL SP Heart Failure Soc Amer (HFSA) C1 [Niehaus, Emily D.; Malhotra, Rajeev; Cocca-Spofford, Diane; Lewis, Gregory D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2013 VL 19 IS 8 SU 1 MA 239 BP S83 EP S83 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201LG UT WOS:000323142500241 ER PT J AU Vigersky, RA Bhasin, S Martin, KA AF Vigersky, Robert A. Bhasin, Shalender Martin, Kathryn A. TI The Endocrine Society Clinical Practice Guidelines: A Self-Assessment SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID TYPE-2 DIABETES-MELLITUS; RECOMMENDATIONS; DEFICIENCY; DIAGNOSIS; STRENGTH; PREVENTION; QUALITY C1 [Vigersky, Robert A.] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Bhasin, Shalender] Brigham & Womens Hosp, Boston, MA 02115 USA. [Martin, Kathryn A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vigersky, RA (reprint author), Walter Reed Natl Mil Med Ctr, Endocrinol & Diabet Serv, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM robert.vigersky@us.army.mil NR 20 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2013 VL 98 IS 8 BP 3174 EP 3177 DI 10.1210/jc.2013-2300 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 196NC UT WOS:000322781300032 PM 23801367 ER PT J AU Gupta, A Ly, S Castroneves, LA Frates, MC Benson, CB Feldman, HA Wassner, AJ Smith, JR Marqusee, E Alexander, EK Barletta, J Doubilet, PM Peters, HE Webb, S Modi, BP Paltiel, HJ Kozakewich, H Cibas, ES Moore, FD Shamberger, RC Larsen, PR Huang, SA AF Gupta, Anjuli Ly, Samantha Castroneves, Luciana A. Frates, Mary C. Benson, Carol B. Feldman, Henry A. Wassner, Ari J. Smith, Jessica R. Marqusee, Ellen Alexander, Erik K. Barletta, Justine Doubilet, Peter M. Peters, Hope E. Webb, Susan Modi, Biren P. Paltiel, Harriet J. Kozakewich, Harry Cibas, Edmund S. Moore, Francis D., Jr. Shamberger, Robert C. Larsen, P. Reed Huang, Stephen A. TI A Standardized Assessment of Thyroid Nodules in Children Confirms Higher Cancer Prevalence Than in Adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FINE-NEEDLE-ASPIRATION; 4 CM; MANAGEMENT; ADOLESCENTS; CYTOLOGY; SURGERY; BIOPSY; EXPERIENCE; CHILDHOOD; DIAGNOSIS AB Context: Thyroid cancer is the most common endocrine malignancy, but due to its rare occurrence in the pediatric population, the cancer risk of childhood thyroid nodules is incompletely defined, and optimal management of children with suspected nodules is debated. Objective: The aim was to study the presenting features and cancer risk of sporadic childhood thyroid nodules using a standardized clinical assessment and management plan. Design and Setting: Boston Children's Hospital and Brigham and Women's Hospital collaborated to create a multidisciplinary pediatric thyroid nodule clinic and implement a standardized assessment plan. Upon referral for a suspected nodule, serum TSH was measured and hypothyrotropinemic patients underwent I-123 scintigraphy. All others underwent thyroid ultrasonography, and if this confirmed nodule(s) >= 1 cm, ultrasound-guided fine-needle aspiration was performed. Medical records were retrospectively reviewed and compared to a control population of 2582 adults evaluated by identical methods. Patients and Results: Of 300 consecutive children referred for the initial evaluation of suspected thyroid nodules from 1997 to 2011, 17 were diagnosed with autonomous nodules by scintigraphy. Neck ultrasonography performed in the remainder revealed that biopsy was unnecessary in over half, either by documenting only sub-centimeter nodules or showing that no nodule was present. A total of 125 children met criteria for thyroid biopsy, which was performed without complication. Their rate of cancer was 22%, significantly higher than the adult rate of 14% (P = .02). Conclusions: Neck ultrasonography and biopsy were key to the evaluation of children with suspected thyroid nodules. Although the relative cancer prevalence of sonographically confirmed nodules >= 1 cm is higher in pediatric patients than adults, most children referred for suspected nodules have benign conditions, and efforts to avoid unnecessary surgery in this majority are warranted. C1 [Gupta, Anjuli; Ly, Samantha; Castroneves, Luciana A.; Feldman, Henry A.; Wassner, Ari J.; Smith, Jessica R.; Webb, Susan; Huang, Stephen A.] Boston Childrens Hosp, Thyroid Program, Div Endocrinol, Boston, MA 02115 USA. [Feldman, Henry A.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Paltiel, Harriet J.] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Kozakewich, Harry] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Modi, Biren P.; Shamberger, Robert C.] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Wassner, Ari J.; Smith, Jessica R.; Marqusee, Ellen; Alexander, Erik K.; Larsen, P. Reed; Huang, Stephen A.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Thyroid Sect, Boston, MA 02115 USA. [Frates, Mary C.; Benson, Carol B.; Doubilet, Peter M.; Peters, Hope E.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Barletta, Justine; Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Moore, Francis D., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Marqusee, Ellen; Alexander, Erik K.; Larsen, P. Reed; Huang, Stephen A.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Huang, SA (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM stephen.huang@childrens.harvard.edu OI Wassner, Ari/0000-0003-0894-9301 FU Murray Family; National Institutes of Health [DK076099, DK007699, DK007529] FX This work was supported by a donation from the Murray Family and by grants DK076099, DK007699 and DK007529 from the National Institutes of Health. NR 35 TC 43 Z9 44 U1 1 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 AUG PY 2013 VL 98 IS 8 BP 3238 EP 3245 DI 10.1210/jc.2013-1796 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 196NC UT WOS:000322781300040 PM 23737541 ER PT J AU Jovanovich, A Buzkova, P Chonchol, M Robbins, J Fink, HA de Boer, IH Kestenbaum, B Katz, R Carbone, L Lee, J Laughlin, GA Mukamal, KJ Fried, LF Shlipak, MG Ix, JH AF Jovanovich, Anna Buzkova, Petra Chonchol, Michel Robbins, John Fink, Howard A. de Boer, Ian H. Kestenbaum, Bryan Katz, Ronit Carbone, Laura Lee, Jennifer Laughlin, Gail A. Mukamal, Kenneth J. Fried, Linda F. Shlipak, Michael G. Ix, Joachim H. TI Fibroblast Growth Factor 23, Bone Mineral Density, and Risk of Hip Fracture Among Older Adults: The Cardiovascular Health Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHRONIC KIDNEY-DISEASE; PHOSPHATE HOMEOSTASIS; CYSTATIN-C; FGF-23; FIBROBLAST-GROWTH-FACTOR-23; OSTEOMALACIA; OSTEOPOROSIS; HEMODIALYSIS; ASSOCIATION; MORTALITY AB Context: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis. Objective: Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults. Design and Setting: Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease. Participants: Participants included 2008 women and 1329 men >= 65 years from the 1996 to 1997 Cardiovascular Health Study visit. Main Outcome Measures: Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants. Results: Women had higher plasma FGF23 concentrations than men (75 [56-107] vs 66 [interquartile range = 52-92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (beta per doubling of FGF23 = 0.02, with 95% confidence interval [CI] = 0.001-0.04 g/cm(2), and 0.03 with 95% CI = 0.01-0.06 g/cm(2)). During 9.6 +/- 5.1-11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men(adjusted hazard ratio = 0.95, with 95% CI = 0.78-1.15, and 1.09 with 95% CI = 0.82-1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions). Conclusions: In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk. C1 [Jovanovich, Anna; Chonchol, Michel] Univ Colorado, Sch Med, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. [Buzkova, Petra; Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98105 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98105 USA. [de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Kidney Res Inst, Seattle, WA 98105 USA. [Robbins, John] Univ Calif Davis, Sacramento, CA 95817 USA. [Fink, Howard A.] Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN 55417 USA. [Carbone, Laura] Dept Vet Affairs Med Ctr, Memphis, TN 38104 USA. [Lee, Jennifer] Calif Pacific Med Ctr, San Francisco Coordinating Ctr, Res Inst, San Francisco, CA 94115 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92161 USA. [Laughlin, Gail A.] Univ Calif San Diego, Div Epidemiol, Dept Family & Prevent Med, San Diego, CA 92093 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, San Diego, CA 92093 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent, Dept Family & Prevent Med, San Diego, CA 92093 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent, Dept Med, San Diego, CA 92093 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu FU National Heart, Lung, and Blood Institute (NHLBI) [R01HL096851]; American Heart Association [0575021N]; NHLBI [U01 HL080295]; [HHSN268201200036C]; [N01 HC-85079]; [N01HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01 HC-75150]; [N01 HC-54133]; [N01-HC-80007] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) (R01HL096851) and American Heart Association (0575021N) to J.H.I. Additionally, this paper was supported in part with resources of the Veterans Affairs San Diego Healthcare System. The Cardiovascular Health Study was supported by contract numbers HHSN268201200036C, N01 HC-85079 through N01HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01 HC-75150, N01 HC-54133, and N01-HC-80007 and Grant U01 HL080295 from the NHLBI, with additional contributions from the National Institute of Neurological Disorders and Stroke. NR 31 TC 9 Z9 9 U1 2 U2 24 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 AUG PY 2013 VL 98 IS 8 BP 3323 EP 3331 DI 10.1210/jc.2013-1152 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 196NC UT WOS:000322781300050 PM 23771921 ER PT J AU Rogg, J Hoffmann, U Truong, Q Brown, DFM Parry, B Nagurney, JT AF Rogg, Jonathan Hoffmann, Udo Quynh Truong Brown, David F. M. Parry, Blair Nagurney, John T. TI EVALUATION OF RENAL FUNCTION TESTS BY AGE AND SEX TO DETERMINE EMERGENCY DEPARTMENT PATIENTS' ELIGIBILITY FOR CARDIAC COMPUTED TOMOGRAPHY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE cardiology; cardiac CT; CCTA; contrast-induced nephropathy; ACS; chest pain ID CONTRAST-INDUCED NEPHROPATHY; PERCUTANEOUS CORONARY INTERVENTION; GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; KIDNEY-FUNCTION; RISK-FACTORS; ENHANCED CT; INSUFFICIENCY; NEPHROTOXICITY; ANGIOGRAPHY AB Background: Coronary computed tomography angiography (CCTA) can be used for low-risk chest pain patients, but presents a risk of contrast-induced nephropathy. Objective: We compared, by age and sex, the percent of patients who would become ineligible for CCTA based on serum creatinine (SCr) and glomerular filtration rate (GFR) cutoff points. Methods: All adult patients who presented to the Emergency Department (ED) with chest pain were screened using their first ED SCr as part of the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) study. This was a secondary analysis of the screening logs of that study. The Modification of Diet in Renal Disease formula was applied to calculate estimated GFR and the percent of patients, by age and sex, meeting commonly applied exclusion criteria using selected SCr and GFR cutoff values. This was our primary outcome. Results: Of 2398 patients screened, 384 (16%) were excluded for high-risk features or technical limitations of CCTA, leaving 2014 patients who were studied; 56% were male. For all cutoff points of SCr (>= 1.3 mg/dL, >= 1.5 mg/dL, >= 1.8 mg/dL), the percent of males excluded significantly exceeded that of females (p < 0.0001 [28.6% males to 18.5% females]; p < 0.0001 [17.4% males to 11.2% females]; p = 0.0004 [10.1% males to 5.8% females], respectively). Conversely, for two of the three cutoff points of GFR (<= 60 mL/min/1.73 m(2) and <= 45 mL/min/1.73 m(2)), the percent of females excluded significantly exceeded that of males (p < 0.0001 [33.6% females to 25.4% males] and p = 0.0015 [17.6% males to 12.5% females], respectively). Conclusions: The choice of SCr or GFR to screen patients for CCTA selectively excludes either males or females, respectively. Therefore, individual physicians and institutions must understand the impact of both renal function tests and cutoff points when identifying patients who may be eligible for CCTA. (C) 2013 Elsevier Inc. C1 [Rogg, Jonathan] Brigham & Womens Hosp, Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. [Hoffmann, Udo; Quynh Truong] Massachusetts Gen Hosp, Dept Radiol, Div Cardiac Imaging, Boston, MA 02114 USA. [Brown, David F. M.; Parry, Blair; Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Emergency Serv 3B, Zero Emerson Pl, Boston, MA 02114 USA. NR 28 TC 1 Z9 1 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2013 VL 45 IS 2 BP 220 EP 226 DI 10.1016/j.jemermed.2013.03.026 PG 7 WC Emergency Medicine SC Emergency Medicine GA 201UL UT WOS:000323168400020 PM 23735846 ER PT J AU Maldonado, NG Nadel, ES Brown, DFM AF Maldonado, Nicholas G. Nadel, Eric S. Brown, David F. M. TI LEFT LOWER EXTREMITY PAIN AND SWELLING SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID PHLEGMASIA-CERULEA-DOLENS; ILIAC VEIN COMPRESSION; MAY-THURNER-SYNDROME; DEEP VENOUS THROMBOSIS; DIAGNOSIS; (MAY-THURNER)-SYNDROME; VENOGRAPHY; PATIENT C1 [Maldonado, Nicholas G.; Nadel, Eric S.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Nadel, Eric S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Founders 114, Boston, MA 02114 USA. NR 31 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2013 VL 45 IS 2 BP 244 EP 251 PG 8 WC Emergency Medicine SC Emergency Medicine GA 201UL UT WOS:000323168400025 PM 23786778 ER PT J AU Nowak, R Farrar, JR Brenner, BE Lewis, L Silverman, RA Emerman, C Hays, DP Russell, WS Schmitz, N Miller, J Singer, E Camargo, CA Wood, J AF Nowak, Richard Farrar, Judith Rosen Brenner, Barry E. Lewis, Lawrence Silverman, Robert A. Emerman, Charles Hays, Daniel P. Russell, W. Scott Schmitz, Natalie Miller, Judi Singer, Ethan Camargo, Carlos A., Jr. Wood, Joseph TI CUSTOMIZING ANAPHYLAXIS GUIDELINES FOR EMERGENCY MEDICINE SO JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE anaphylaxis; guidelines; epinephrine (adrenaline); allergic reaction; life-threatening reaction ID SELF-INJECTABLE EPINEPHRINE; WORLD ALLERGY ORGANIZATION; DEPARTMENT PATIENTS; NATIONAL INSTITUTE; MANAGEMENT; EPIDEMIOLOGY; DEFINITION; CHILDREN; VISITS; MULTICENTER AB Background: Most episodes of anaphylaxis are managed in emergency medical settings, where the cardinal signs and symptoms often differ from those observed in the allergy clinic. Data suggest that low recognition of anaphylaxis in the emergency setting may relate to inaccurate coding and lack of a standard, practical definition. Objective: Develop a simple, consistent definition of anaphylaxis for emergency medicine providers, supported by clinically relevant consensus statements. Discussion: Definitions of anaphylaxis and criteria for diagnosis from current anaphylaxis guidelines were reviewed with regard to their utilization in emergency medical settings. The agreed-upon working definition is: Anaphylaxis is a serious reaction causing a combination of characteristic findings, and which is rapid in onset and may cause death. It is usually due to an allergic reaction but can be non-allergic. The definition is supported by Consensus Statements, each with referenced discussion. For a positive outcome, quick diagnosis and treatment of anaphylaxis are critical. However, even in the emergency setting, the patient may not present with life-threatening symptoms. Because mild initial symptoms can quickly progress to a severe, even fatal, reaction, the first-line treatment for any anaphylaxis episode-regardless of severity-is intramuscular injection of epinephrine into the anterolateral thigh; delaying its administration increases the potential for morbidity and mortality. When a reaction appears as "possible anaphylaxis," it is generally better to err on the side of caution and administer epinephrine. Conclusion: We believe that this working definition and the supporting Consensus Statements are a first step to better management of anaphylaxis in the emergency medical setting. (C) 2013 Elsevier Inc. C1 [Nowak, Richard] Univ Michigan, Sch Med, Wayne State Univ, Detroit, MI USA. [Farrar, Judith Rosen] Life Sci Press, Canandaigua, NY USA. [Brenner, Barry E.] Case Western Reserve Sch Med, Cleveland, OH USA. [Lewis, Lawrence] Washington Univ, Sch Med, St Louis, MO USA. [Silverman, Robert A.] North Shore Long Isl Jewish Hosp Syst, New Hyde Pk, NY USA. [Emerman, Charles] Cleveland Clin, Cleveland, OH 44106 USA. [Hays, Daniel P.] Univ Arizona, Med Ctr, Tucson, AZ USA. [Russell, W. Scott] Med Univ S Carolina, Charleston, SC 29425 USA. [Schmitz, Natalie] DeKalb Med Ctr, Atlanta, GA USA. [Miller, Judi] SRxA, Washington, DC USA. [Singer, Ethan] Catskill Reg Med Ctr, Callicoon, NY USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wood, Joseph] Mayo Clin Arizona, Scottsdale, AZ USA. RP Nowak, R (reprint author), Henry Ford Hosp, Dept Emergency Med, 2799 W Grand Blvd, Detroit, MI 48202 USA. FU Mylan Pharmaceuticals FX This manuscript was supported in part by an unrestricted educational grant from Mylan Pharmaceuticals. The company had no involvement in the development, writing, or review of the manuscript. All authors participated in the original Roundtable meeting, Anaphylaxis in Emergency Medicine, convened in Chicago, IL in July 2011, and agreed at that time that there exists a need for a standard definition of anaphylaxis that is appropriate for emergency medicine health professionals. Richard Nowak, MD, chaired the Roundtable meeting and the subsequent meeting of the authors (March 2012) to discuss the definition and consensus statements. Judith Farrar, PHD, drafted the discussion summary on which the manuscript was based; and the authors then used the summary to develop/write the consensus statements and the supporting discussion for each. The authors also all contributed substantially to revising drafts of the full manuscript, and all have agreed to this final version of the paper. NR 34 TC 7 Z9 7 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2013 VL 45 IS 2 BP 299 EP 305 DI 10.1016/j.jemermed.2013.01.018 PG 7 WC Emergency Medicine SC Emergency Medicine GA 201UL UT WOS:000323168400036 PM 23643240 ER PT J AU Duckworth, AD Jenkins, PJ Roddam, P Watts, AC Ring, D McEachan, JE AF Duckworth, Andrew D. Jenkins, Paul J. Roddam, Philip Watts, Adam C. Ring, David McEachan, Jane E. TI Pain and Carpal Tunnel Syndrome SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Carpal tunnel syndrome; pain; diagnosis; nerve conduction studies; outcome ID IDIOPATHIC ARM PAIN; SOCIOECONOMIC DEPRIVATION; DIABETES-MELLITUS; SMOKING; QUESTIONNAIRE; PREDICTORS; DIAGNOSIS; RELEASE; NICOTINE; OBESITY AB Purpose Pain is not a classical symptom of carpal tunnel syndrome (CTS), with the exception of numbness that is so intense that it is described by patients as painful The primary aim of our study was to determine which factors correlated with pain for patients diagnosed with CTS. Methods We prospectively assessed all patients diagnosed with CTS in our unit over a 1-year period. We recorded demographic details for all patients, including past medical history, body mass index, smoking, and occupation. The diagnosis and severity of carpal tunnel syndrome were established through a combination of history, clinical assessment, and nerve conduction studies. Of 275 patients diagnosed and treated for CTS, 183 were women (67%), the mean age was 55 years (range, 22-87 y), and 166 cases were bilateral (60%). The mean body mass index was 29.5 kg/m(2) (range, 17-48 kg/m(2)), and 81 patients smoked (30%). Patients completed a Short Form-McGill pain questionnaire (SF-MPQ) as a measure of pain at initial presentation. We assessed outcome 1 year after intervention using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. Results We found no association between pain according to the SF-MPQ and the positive clinical signs of CTS or positive nerve conduction studies. Multivariate analysis demonstrated that smoking and bilateral disease independently correlated with the overall SF-MPQ, with similar findings on subanalysis. Independent factors associated with an increased improvement in the QuickDASH at 1 year were the presentation QuickDASH score, positive nerve conduction studies, and smoking. Conclusions The only independent factors that correlated with pain at presentation of CTS were smoking and bilateral disease. Pain according to the SF-MPQ was not associated with classical clinical findings of the disease or with positive findings on nerve conduction testing. (Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Duckworth, Andrew D.] Queen Margaret Hosp, Dept Orthopaed Surg, Dunfermline KY12 0SU, Fife, Scotland. Wrightington Hosp, Upper Limb Unit, Wigan, Lancs, England. Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Duckworth, AD (reprint author), Queen Margaret Hosp, Dept Orthopaed Surg, Whitefield Rd, Dunfermline KY12 0SU, Fife, Scotland. EM andrew.duckworth@yahoo.co.uk NR 45 TC 4 Z9 4 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD AUG PY 2013 VL 38A IS 8 BP 1540 EP 1546 DI 10.1016/j.jhsa.2013.05.027 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 198LZ UT WOS:000322925700012 PM 23890497 ER PT J AU Cross, DJ Anzai, Y Petrie, EC Martin, N Richards, TL Maravilla, KR Peskind, ER Minoshima, S AF Cross, Donna J. Anzai, Yoshimi Petrie, Eric C. Martin, Nathalie Richards, Todd L. Maravilla, Kenneth R. Peskind, Elaine R. Minoshima, Satoshi TI Loss of Olfactory Tract Integrity Affects Cortical Metabolism in the Brain and Olfactory Regions in Aging and Mild Cognitive Impairment SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE olfactory tract; Alzheimer's disease; fiber tract integrity; glucose metabolism; F-18-FDG PET; DTI ID TRAUMATIC AXONAL INJURY; ALZHEIMERS-DISEASE; TAU PATHOLOGY; IN-VIVO; DYSFUNCTION; MRI; EPSILON-4; BULB; PET AB Olfactory dysfunction is an early feature of Alzheimer disease. This study used multimodal imaging of PET and F-18-FDG combined with diffusion tensor imaging (DTI) to investigate the association of fiber tract integrity in the olfactory tract with cortical glucose metabolism in subjects with mild cognitive impairment (MCI) and normal controls. We hypothesized that MCI subjects would show loss of olfactory tract integrity and may have altered associations with glucose metabolism. Methods: Subjects diagnosed with amnestic MCI (n = 12) and normal controls (n = 23) received standard brain F-18-FDG PET and DTI with 32 gradient directions on a 3-T MR imaging scanner. Fractional anisotropy (FA) maps were generated. Voxelwise correlation analysis of olfactory tract FA values with F-18-FDG PET images was performed. Results: Integrated analysis over all subjects indicated a positive correlation between white matter integrity in the olfactory tract and metabolic activity in olfactory processing structures, including the rostral prefrontal cortex, dorsomedial thalamus, hypothalamus, orbitofrontal cortex, and uncus, and in the superior temporal gyrus, insula, and anterior cingulate cortex. Subjects with MCI, compared with normal controls, showed differential associations of olfactory tract integrity with medial temporal lobe and posterior cortical structures. Conclusion: These findings indicate that impairment of axonal integrity or neuronal loss may be linked to functional metabolic changes and that disease-specific neurodegeneration may affect this relationship. Multimodal imaging using F-18-FDG PET and DTI may provide better insights into aging and neurodegenerative processes. C1 [Cross, Donna J.; Anzai, Yoshimi; Petrie, Eric C.; Martin, Nathalie; Richards, Todd L.; Maravilla, Kenneth R.; Minoshima, Satoshi] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Petrie, Eric C.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Petrie, Eric C.; Peskind, Elaine R.] MIRECC, VA Puget Sound, Seattle, WA USA. RP Cross, DJ (reprint author), Univ Washington, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM dcross@uw.edu FU NIH [R01 NS045254]; NIA [P50AG005136]; VA Puget Sound Mental Illness Research, Education and Clinical Center (MIRECC) FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This study was supported by NIH R01 NS045254, NIA grant P50AG005136, and the VA Puget Sound Mental Illness Research, Education and Clinical Center (MIRECC). No other potential conflict of interest relevant to this article was reported. NR 31 TC 13 Z9 14 U1 0 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 2013 VL 54 IS 8 BP 1278 EP 1284 DI 10.2967/jnumed.112.116558 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 195HH UT WOS:000322692400035 PM 23804325 ER PT J AU Zeglis, BM Sevak, KK Reiner, T Mohindra, P Carlin, SD Zanzonico, P Weissleder, R Lewis, JS AF Zeglis, Brian M. Sevak, Kuntal K. Reiner, Thomas Mohindra, Priya Carlin, Sean D. Zanzonico, Pat Weissleder, Ralph Lewis, Jason S. TI A Pretargeted PET Imaging Strategy Based on Bioorthogonal Diels-Alder Click Chemistry SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE positron emission tomography (PET); pretargeting; click chemistry; antibody; colorectal cancer ID RADIOIMMUNOTHERAPY; CANCER; ANTIBODIES; THERAPY; A33 AB The specificity of antibodies have made immunoconjugates promising vectors for the delivery of radioisotopes to cancer cells; however, their long pharmacologic half-lives necessitate the use of radioisotopes with long physical half-lives, a combination that leads to high radiation doses to patients. Therefore, the development of targeting modalities that harness the advantages of antibodies without their pharmacokinetic limitations is desirable. To this end, we report the development of a methodology for pretargeted PET imaging based on the bioorthogonal Diels-Alder click reaction between tetrazine and transcyclooctene. Methods: A proof-of-concept system based on the A33 antibody, SW1222 colorectal cancer cells, and Cu-64 was used. The huA33 antibody was covalently modified with transcyclooctene, and a NOTA-modified tetrazine was synthesized and radiolabeled with Cu-64. Pretargeted in vivo biodistribution and PET imaging experiments were performed with athymic nude mice bearing A33 antigen-expressing, SW1222 colorectal cancer xenografts. Results: The huA33 antibody was modified with transcyclooctene to produce a conjugate with high immunoreactivity, and the Cu-64-NOTA-labeled tetrazine ligand was synthesized with greater than 99% purity and a specific activity of 9-10 MBq/mu g. For in vivo experiments, mice bearing SW1222 xenografts were injected with transcyclooctene-modified A33; after allowing 24 h for accumulation of the antibody in the tumor, the mice were injected with Cu-64-NOTA-labeled tetrazine for PET imaging and biodistribution experiments. At 12 h after injection, the retention of uptake in the tumor (4.1 +/- 0.3 percent injected dose per gram), coupled with the fecal excretion of excess radioligand, produced images with high tumor-to-background ratios. PET imaging and biodistribution experiments performed using A33 directly labeled with either Cu-64 or Zr-89 revealed that although absolute tumor uptake was higher with the directly radiolabeled antibodies, the pretargeted system yielded comparable images and tumor-to-muscle ratios at 12 and 24 h after injection. Further, dosimetry calculations revealed that the Cu-64 pretargeting system resulted in only a fraction of the absorbed background dose of A33 directly labeled with Zr-89 (0.0124 mSv/MBq vs. 0.4162 mSv/MBq, respectively). Conclusion: The high quality of the images produced by this pretargeting approach, combined with the ability of the methodology to dramatically reduce nontarget radiation doses to patients, marks this system as a strong candidate for clinical translation. C1 [Zeglis, Brian M.; Sevak, Kuntal K.; Reiner, Thomas; Mohindra, Priya; Carlin, Sean D.; Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Zanzonico, Pat] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Lewis, JS (reprint author), 1275 York Ave, New York, NY 10065 USA. EM lewisj2@mskcc.org OI Carlin, Sean/0000-0002-5401-0648; Reiner, Thomas/0000-0002-7819-5480 FU NIH [1F32CA1440138-01, R01EB010011, P50-CA86355, R24-CA83084, P30-CA08748]; DOE [DE-SC0002184, DE-SC0002456] FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work received financial support from the NIH (1F32CA1440138-01, R01EB010011, and P50-CA86355) and the DOE (DE-SC0002184 and DE-SC0002456). Services provided by the MSKCC Small-Animal Imaging Core Facility were supported in part by NIH grants R24-CA83084 and P30-CA08748. No other potential conflict of interest relevant to this article was reported. NR 25 TC 76 Z9 77 U1 12 U2 99 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 AUG PY 2013 VL 54 IS 8 BP 1389 EP 1396 DI 10.2967/jnumed.112.115840 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 195HH UT WOS:000322692400052 PM 23708196 ER PT J AU Dorbala, S Di Carli, MF Delbeke, D Abbara, S DePuey, EG Dilsizian, V Forrester, J Janowitz, W Kaufmann, PA Mahmarian, J Moore, SC Stabin, MG Shreve, P AF Dorbala, Sharmila Di Carli, Marcelo F. Delbeke, Dominique Abbara, Suhny DePuey, E. Gordon Dilsizian, Vasken Forrester, Joey Janowitz, Warren Kaufmann, Philipp A. Mahmarian, John Moore, Stephen C. Stabin, Michael G. Shreve, Paul TI SNMMI/ASNC/SCCT Guideline for Cardiac SPECT/CT and PET/CT 1.0 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; MYOCARDIAL-PERFUSION SPECT; AMERICAN-HEART-ASSOCIATION; EMISSION COMPUTED-TOMOGRAPHY; 64-SLICE CT ANGIOGRAPHY; LOW-DOSE CT; STATISTICAL ITERATIVE RECONSTRUCTION; CARDIOVASCULAR MAGNETIC-RESONANCE; APPROPRIATE USE CRITERIA; STRESS-INDUCED ISCHEMIA C1 [Dorbala, Sharmila; Di Carli, Marcelo F.; Moore, Stephen C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Delbeke, Dominique; Forrester, Joey; Stabin, Michael G.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Abbara, Suhny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [DePuey, E. Gordon] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Dilsizian, Vasken] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Janowitz, Warren] Baptist Hosp Miami, Miami, FL USA. [Kaufmann, Philipp A.] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Mahmarian, John] Methodist Hosp, Houston, TX 77030 USA. [Shreve, Paul] Adv Radiol Serv, Grand Rapids, MI USA. RP Dorbala, S (reprint author), Brigham & Womens Hosp, 70 Francis St, Boston, MA 02115 USA. EM sdorbala@partners.org NR 148 TC 36 Z9 36 U1 1 U2 4 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 AUG PY 2013 VL 54 IS 8 BP 1485 EP 1507 DI 10.2967/jnumed.112.105155 PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 195HH UT WOS:000322692400065 PM 23781013 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Lucky to Be an Oncologist 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 02115 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 0 TC 0 Z9 0 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD AUG PY 2013 VL 11 IS 8 BP 909 EP 910 PG 2 WC Oncology SC Oncology GA 201QE UT WOS:000323156900001 PM 23946169 ER PT J AU Pfister, DG Ang, KK Brizel, DM Burtness, BA Busse, PM Caudell, JJ Cmelak, AJ Colevas, AD Dunphy, F Eisele, DW Gilbert, J Gillison, ML Haddad, RI Haughey, BH Hicks, WL Hitchcock, YJ Kies, MS Lydiatt, WM Maghami, E Martins, R McCaffrey, T Mittal, BB Pinto, HA Ridge, JA Samant, S Schuller, DE Shah, JP Spencer, S Weber, RS Wolf, GT Worden, F Yom, SS McMillian, NR Hughes, M AF Pfister, David G. Ang, Kie-Kian Brizel, David M. Burtness, Barbara A. Busse, Paul M. Caudell, Jimmy J. Cmelak, Anthony J. Colevas, A. Dimitrios Dunphy, Frank Eisele, David W. Gilbert, Jill Gillison, Maura L. Haddad, Robert I. Haughey, Bruce H. Hicks, Wesley L. Hitchcock, Ying J. Kies, Merrill S. Lydiatt, William M. Maghami, Ellie Martins, Renato McCaffrey, Thomas Mittal, Bharat B. Pinto, Harlan A. Ridge, John A. Samant, Sandeep Schuller, David E. Shah, Jatin P. Spencer, Sharon Weber, Randal S. Wolf, Gregory T. Worden, Frank Yom, Sue S. McMillian, Nicole R. Hughes, Miranda TI Head and Neck Cancers, Version 2.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ENDOSCOPIC GASTROSTOMY TUBE; QUALITY-OF-LIFE; WEIGHT-LOSS; NASOGASTRIC TUBE; PLACEMENT; RADIOTHERAPY; CHEMORADIOTHERAPY; PREDICTORS; CARCINOMA; NUTRITION AB These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org). (JNCCN 2013; 11: 917-923) C1 [Pfister, David G.; Shah, Jatin P.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ang, Kie-Kian] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Burtness, Barbara A.; Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Busse, Paul M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Caudell, Jimmy J.; McCaffrey, Thomas] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Cmelak, Anthony J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Colevas, A. Dimitrios] Stanford Canc Inst, Stanford, CA USA. [Eisele, David W.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Gillison, Maura L.; Schuller, David E.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Gillison, Maura L.; Schuller, David E.] Solove Res Inst, Columbus, OH USA. [Haddad, Robert I.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Haughey, Bruce H.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Haughey, Bruce H.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Hicks, Wesley L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hitchcock, Ying J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Lydiatt, William M.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Maghami, Ellie] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Martins, Renato] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Mittal, Bharat B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Samant, Sandeep] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Spencer, Sharon] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Wolf, Gregory T.; Worden, Frank] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Yom, Sue S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Pfister, DG (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. OI Shah, Jatin/0000-0002-6444-6592 FU Genentech, Inc.; Novartis Pharmaceuticals; Bayer HealthCare; Exelixis Inc.; ActoGeniX NV; Boehringer Ingelheim GmbH; GlaxoSmithKline; Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals; HealthTronics; Genentech; ARIAD Pharmaceuticals, Inc. FX Dr. Burtness: Advisor for Bristol-Myers Squibb Company. Research funding from Genentech, Inc. and Novartis Pharmaceuticals; Dr. Colevas: Clinical research support from Bayer HealthCare; Exelixis Inc.; Genentech, Inc.; and ActoGeniX NV. Research funding from Boehringer Ingelheim GmbH and GlaxoSmithKline. Serves on the Head and Neck Steering Subcommittee for NCI. Site investigator for RTOG and ECOG. Committee member for ECOG.; Dr. Martins: PI for Bayer HealthCare; Eisai Inc.; Genentech, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer Inc. Clinical research support from Exelixis Inc.; Supported by educational grants from Eisai, Inc.; Millennium: The Takeda Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.; Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech; and ARIAD Pharmaceuticals, Inc. NR 32 TC 62 Z9 68 U1 3 U2 8 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 AUG PY 2013 VL 11 IS 8 BP 917 EP 923 PG 7 WC Oncology SC Oncology GA 201QE UT WOS:000323156900003 PM 23946171 ER PT J AU Lloyd, S Buscariollo, DL Gross, CP Makarov, DV Yu, JB AF Lloyd, Shane Buscariollo, Daniela L. Gross, Cary P. Makarov, Danil V. Yu, James B. TI Determinants of Enrollment in Cancer Clinical Trials: The Relationship Between the Current State of Knowledge, Societal Disease Burden, and Randomized Clinical Trial Enrollment SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RECOMMENDATIONS AB Whether clinical cancer research currently focuses on gaps in the evidentiary basis for clinical guidelines and/or on cancers that impose greater societal burden is unclear. This study assessed the relationship between cancer research efforts in terms of planned randomized controlled trial (RCT) enrollment, objective measures of evidence quality, and a cancer's burden on society. The authors calculated the planned RCT enrollment listed on ClinicalTrials.gov for the 17 most prevalent solid cancers. Using cancer type as the unit of analysis, linear regression was used to examine the association between planned enrollment in RCTs and 1) evidence quality, as measured by the absolute number and percent of highest quality category (category 1 [C1]) recommendations in the NCCN Clinical Practice Guidelines in Oncology for each cancer, and 2) measures of burden on society, including prevalence, incidence, person-years of life lost (PYLL), and disability-adjusted life years (DALY). Non-normal distributions were log transformed when appropriate. Overall, 15% of the NCCN recommendations were based on the highest quality evidence. Results produced 1260 RCTs. Planned RCT enrollment ranged from 2270 (testis) to 492,876 (breast) and was correlated neither with absolute number nor percent of C1 recommendations for that cancer. Planned RCT enrollment was positively correlated with a cancer's prevalence (P=.01), incidence (P<.01), PYLL (P<.01), and DALY (P<0.01). In multivariate analysis, prevalence (P<.01) and PYLL (P<.01) had the strongest association with planned RCT enrollment. Findings showed, therefore, that planned cancer RCT enrollment is associated with higher societal disease burden, not the quality of a cancer's clinical guidelines. C1 [Lloyd, Shane; Yu, James B.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Buscariollo, Daniela L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gross, Cary P.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Makarov, Danil V.] NYU, Sch Med, Dept Urol, US Dept Vet Affairs, New York, NY 10003 USA. [Makarov, Danil V.] NYU, Sch Med, US Dept Vet Affairs, Dept Populat Hlth & Canc, New York, NY 10003 USA. RP Yu, JB (reprint author), Yale Univ, Sch Med, Dept Therapeut Radiol, LL 516 Smilow,POB 208040, New Haven, CT 06510 USA. EM james.b.yu@yale.edu FU Medtronic FX Drs. Lloyd, Buscariollo, Makarov, and Yu have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. Dr. Gross has disclosed that he receives a research grant from Medtronic and is on the advisory board for Fair Health Inc. NR 18 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2013 VL 11 IS 8 BP 928 EP 936 PG 9 WC Oncology SC Oncology GA 201QE UT WOS:000323156900004 PM 23946172 ER PT J AU Chen, RC Shipley, WU Efstathiou, JA Zietman, AL AF Chen, Ronald C. Shipley, William U. Efstathiou, Jason A. Zietman, Anthony L. TI Trimodality Bladder Preservation Therapy for Muscle-Invasive Bladder Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PHASE I-II; SELECTIVE ORGAN PRESERVATION; COMBINED-MODALITY THERAPY; QUALITY-OF-LIFE; RADICAL CYSTECTOMY; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; COMBINED RADIATION; PROSPECTIVE TRIAL; SPARING THERAPY AB Potentially curative treatments for patients with muscle-invasive bladder cancer (MIBC) are underused, especially in the elderly. Trimodality bladder preservation therapy, which includes a maximally safe transurethral resection of the bladder tumor, followed by concurrent chemoradiation, fulfills this currently unmet need. In multiple prospective clinical trials and large institutional series, trimodality therapy has demonstrated excellent 5-year overall survival rates of 48% to 65%, comparable to those reported in cystectomy studies. Approximately 75% to 80% of long-term survivors maintain their native bladders, which tend to function well and allow patients to maintain excellent quality of life. Salvage cystectomy for patients who develop a local invasive recurrence can be performed with acceptable operative complication rates, and results in excellent long-term disease control and survival outcomes. For patients with MIBC who are noncystectomy candidates, or select patients who are motivated to keep their native bladders, trimodality bladder preservation therapy is recognized by the International Consultation on Urological Diseases-European Association of Urology and the NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer as an effective alternative to radical cystectomy, and should be considered. In the future, biomarkers may allow improved selection of patients for whom trimodality bladder preservation therapy is most likely to succeed. C1 [Chen, Ronald C.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. [Shipley, William U.; Efstathiou, Jason A.; Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Chen, RC (reprint author), Univ N Carolina, Dept Radiat Oncol, 101 Manning Dr,CB 7512, Chapel Hill, NC 27599 USA. EM ronald_chen@med.unc.edu NR 40 TC 17 Z9 18 U1 0 U2 9 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD AUG PY 2013 VL 11 IS 8 BP 952 EP 960 PG 9 WC Oncology SC Oncology GA 201QE UT WOS:000323156900006 PM 23946174 ER PT J AU Swarm, RA Abernethy, AP Anghelescu, DL Benedetti, C Buga, S Cleeland, C DeLeon-Casasola, OA Eilers, JG Ferrell, B Green, M Janjan, NA Kamdar, MM Levy, MH Lynch, M McDowell, RM Moryl, N Nesbit, SA Paice, JA Rabow, MW Syrjala, KL Urba, SG Weinstein, SM Dwyer, M Kumar, R AF Swarm, Robert A. Abernethy, Amy Pickar Anghelescu, Doralina L. Benedetti, Costantino Buga, Sorin Cleeland, Charles DeLeon-Casasola, Oscar A. Eilers, June G. Ferrell, Betty Green, Mark Janjan, Nora A. Kamdar, Mihir M. Levy, Michael H. Lynch, Maureen McDowell, Rachel M. Moryl, Natalie Nesbit, Suzanne A. Paice, Judith A. Rabow, Michael W. Syrjala, Karen L. Urba, Susan G. Weinstein, Sharon M. Dwyer, Mary Kumar, Rashmi TI Adult Cancer Pain Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID OPIOID-INDUCED CONSTIPATION; FENTANYL BUCCAL TABLET; CONTROLLED PHASE-III; QUALITY-OF-LIFE; DIABETIC PERIPHERAL NEUROPATHY; OXYCODONE CONTROLLED-RELEASE; TAPENTADOL EXTENDED-RELEASE; RANDOMIZED CONTROLLED-TRIAL; METASTATIC BONE-DISEASE; CHRONIC NONCANCER PAIN AB Pain is a common symptom associated with cancer and its treatment. Pain management is an important aspect of oncologic care, and unrelieved pain significantly comprises overall quality of life. These NCCN Guidelines list the principles of management and acknowledge the range of complex decisions faced in the management oncologic pain. In addition to pain assessment techniques, these guidelines provide principles of use, dosing, management of adverse effects, and safe handling procedures of pharmacologic therapies and discuss a multidisciplinary approach for the management of cancer pain. C1 [Swarm, Robert A.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Anghelescu, Doralina L.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Benedetti, Costantino] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Cleeland, Charles; Janjan, Nora A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [DeLeon-Casasola, Oscar A.] Roswell Pk Canc Inst, Buffalo, NY USA. [Eilers, June G.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Kamdar, Mihir M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Levy, Michael H.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [McDowell, Rachel M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Moryl, Natalie] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Paice, Judith A.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Rabow, Michael W.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Syrjala, Karen L.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Weinstein, Sharon M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. FU NCI NIH HHS [R01 CA160684] NR 164 TC 20 Z9 26 U1 3 U2 17 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 AUG PY 2013 VL 11 IS 8 BP 992 EP 1022 PG 31 WC Oncology SC Oncology GA 201QE UT WOS:000323156900009 PM 23946177 ER PT J AU Goodson, JT Lefkowitz, CM Helstrom, AW Gawrysiak, MJ AF Goodson, Jason T. Lefkowitz, Carin M. Helstrom, Amy W. Gawrysiak, Michael J. TI Outcomes of Prolonged Exposure Therapy for Veterans With Posttraumatic Stress Disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID PSYCHOLOGICAL TREATMENTS; COMPENSATION-SEEKING; PTSD; IRAQ; WAR; PSYCHOTHERAPY; METAANALYSIS; TRIAL; MOOD; PAIN AB Prolonged Exposure (PE) is an evidenced-based psychotherapy for posttraumatic stress disorder (PTSD) that is being disseminated nationally within the U.S. Department of Veterans Affairs (VA) with promising initial results. Empirical evidence, however, regarding the effectiveness of PE for treatment of PTSD in military veterans is limited. Building on previous treatment outcome research, the current study investigated the effectiveness of PE in a diverse veteran sample. One-hundred fifteen veterans were enrolled in PE at an urban VA medical center and its surrounding outpatient clinics. PTSD and depression symptoms as well as quality of life were measured before and after treatment. Several baseline patient characteristics were examined as predictors of treatment response. Eighty-four participants completed treatment. Participants experienced a 42% reduction in PTSD symptoms, a 31% reduction in depression symptoms, and an increase in quality of life following PE. Veterans not prescribed psychotropic medication reported greater PTSD symptom reduction than veterans prescribed such medication. The implications of these results for treatment programs targeting PTSD in veterans are discussed. C1 [Goodson, Jason T.; Lefkowitz, Carin M.; Helstrom, Amy W.; Gawrysiak, Michael J.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Goodson, Jason T.; Lefkowitz, Carin M.; Helstrom, Amy W.; Gawrysiak, Michael J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Goodson, JT (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Jason.Goodson@va.gov NR 40 TC 20 Z9 20 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2013 VL 26 IS 4 BP 419 EP 425 DI 10.1002/jts.21830 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 198CD UT WOS:000322898400001 PM 23934939 ER PT J AU Kearney, DJ Malte, CA McManus, C Martinez, ME Felleman, B Simpson, TL AF Kearney, David J. Malte, Carol A. McManus, Carolyn Martinez, Michelle E. Felleman, Ben Simpson, Tracy L. TI Loving-Kindness Meditation for Posttraumatic Stress Disorder: A Pilot Study SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ADMINISTERED PTSD SCALE; ALTERNATIVE MEDICINE; MILITARY VETERANS; SELF-COMPASSION; MINDFULNESS; COMPLEMENTARY; CLINICIAN; SYMPTOMS; THERAPY; PSYCHOTHERAPY AB Loving-kindness meditation is a practice designed to enhance feelings of kindness and compassion for self and others. Loving-kindness meditation involves repetition of phrases of positive intention for self and others. We undertook an open pilot trial of loving-kindness meditation for veterans with posttraumatic stress disorder (PTSD). Measures of PTSD, depression, self-compassion, and mindfulness were obtained at baseline, after a 12-week loving-kindness meditation course, and 3 months later. Effect sizes were calculated from baseline to each follow-up point, and self-compassion was assessed as a mediator. Attendance was high; 74% attended 9-12 classes. Self-compassion increased with large effect sizes and mindfulness increased with medium to large effect sizes. A large effect size was found for PTSD symptoms at 3-month follow-up (d = -0.89), and a medium effect size was found for depression at 3-month follow-up (d = -0.49). There was evidence of mediation of reductions in PTSD symptoms and depression by enhanced self-compassion. Overall, loving-kindness meditation appeared safe and acceptable and was associated with reduced symptoms of PTSD and depression. Additional study of loving-kindness meditation for PTSD is warranted to determine whether the changes seen are due to the loving-kindness meditation intervention versus other influences, including concurrent receipt of other treatments. C1 [Kearney, David J.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Kearney, David J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Malte, Carol A.; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [McManus, Carolyn] Swedish Med Ctr, Dept Phys Therapy, Seattle, WA USA. [Martinez, Michelle E.; Felleman, Ben] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Simpson, Tracy L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM david.kearney@va.gov NR 40 TC 33 Z9 33 U1 6 U2 52 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2013 VL 26 IS 4 BP 426 EP 434 DI 10.1002/jts.21832 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 198CD UT WOS:000322898400002 PM 23893519 ER PT J AU Franz, MR Wolf, EJ MacDonald, HZ Marx, BP Proctor, SP Vasterling, JJ AF Franz, Molly R. Wolf, Erika J. MacDonald, Helen Z. Marx, Brian P. Proctor, Susan P. Vasterling, Jennifer J. TI Relationships Among Predeployment Risk Factors, Warzone-Threat Appraisal, and Postdeployment PTSD Symptoms SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEUROCOGNITION DEPLOYMENT HEALTH; MENTAL-HEALTH; PROSPECTIVE COHORT; VIETNAM VETERANS; MILITARY SERVICE; FIT INDEXES; IRAQ; AFGHANISTAN; EXPERIENCES AB Previous research indicates a relationship between perceived fear for one's safety (i.e., threat appraisal) and posttraumatic stress disorder (PTSD). This prospective study examined relationships among deployment- and predeployment-related variables, threat appraisal, and postdeployment PTSD symptom severity. Prior to Iraq deployment, 774 U.S. Army soldiers completed self-report measures assessing previous life stressors, deployment history, current (predeployment) PTSD symptoms, deployment preparedness, and unit cohesion. Following deployment, participants completed self-report measures assessing combat intensity, deployment threat appraisal, and current (postdeployment) PTSD symptoms. Structural equation modeling revealed that predeployment PTSD symptom severity, prior warzone deployment, unit cohesion, and preparedness were each independently associated with deployment threat appraisal, even after taking into account combat intensity. Deployment threat appraisal was associated with postdeployment PTSD severity. Results indicated that predeployment PTSD symptom severity, history of warzone deployment, and preparednessrisk factors previously thought to influence PTSD outcomes directlywere either partially or fully mediated by threat appraisal. The model explained 15% of the variance in deployment threat appraisal and 50% of the variance in postdeployment PTSD severity. Helping service members cope with exposure to extreme stress during deployment by modifying certain prewar risk factors may facilitate reduction of PTSD symptoms following deployment. C1 [Franz, Molly R.; MacDonald, Helen Z.; Proctor, Susan P.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Wolf, Erika J.; Marx, Brian P.; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Wolf, Erika J.; Marx, Brian P.; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. [Wolf, Erika J.; MacDonald, Helen Z.; Marx, Brian P.; Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Proctor, Susan P.] US Army Res Inst Environm Med, Mil Performance Div, Natick, MA USA. RP Vasterling, JJ (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B, Boston, MA 02130 USA. EM jennifer.vasterling@va.gov OI Wolf, Erika/0000-0003-2666-2435 NR 35 TC 10 Z9 10 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2013 VL 26 IS 4 BP 498 EP 506 DI 10.1002/jts.21827 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 198CD UT WOS:000322898400011 PM 23893499 ER PT J AU Creech, SK Benzer, JK Liebsack, BK Proctor, S Taft, CT AF Creech, Suzannah K. Benzer, Justin K. Liebsack, Brittany K. Proctor, Susan Taft, Casey T. TI Impact of Coping Style and PTSD on Family Functioning After Deployment in Operation Desert Shield/Storm Returnees SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GULF-WAR VETERANS; COUPLE ADJUSTMENT; SYMPTOMS; VALIDITY AB The relationship between military combat and postdeployment family functioning difficulties has been frequently investigated in the literature, as has the relationship between types of coping and posttraumatic stress disorder (PTSD). Few studies, however, have examined these variables together, and no studies of which we are aware have examined the effect of coping on family functioning after combat exposure. This study examined coping style measured immediately after return from deployment, and PTSD symptoms and family functioning 18-24 months after return from deployment in a sample of Operation Desert Shield/Storm veterans (N = 2,949). Structural equation models suggested that the relationships between distinct coping styles on family functioning were differentially mediated by postdeployment PTSD symptoms. Results are consistent with full mediation for avoidant coping ((direct) = -.09, p = .07; (indirect) = -.17, p < .001) and partial mediation for approach coping ((direct) = .16, p < .001; (indirect) = .09, p < .001). Results suggest that the strategies used to cope with a combat stress event may impact both PTSD and family functioning outcomes, and highlight the potential utility of pre- and postdeployment coping skills training. C1 [Creech, Suzannah K.; Liebsack, Brittany K.; Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Creech, Suzannah K.] Providence VA Med Ctr, Vulnerable Vet Populat Res Grp, Providence, RI USA. [Creech, Suzannah K.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Benzer, Justin K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Benzer, Justin K.] Boston Univ, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Proctor, Susan] US Army Res Inst Environm Med, Mil Performance Div, Natick, MA USA. [Proctor, Susan] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Proctor, Susan] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Creech, SK (reprint author), Providence VAMC, 830 Chalkstone Ave, Providence, RI 02908 USA. EM Suzannah.Creech@va.gov OI Benzer, Justin/0000-0001-5151-2127; Creech, Suzannah/0000-0002-6582-1673 NR 22 TC 4 Z9 4 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2013 VL 26 IS 4 BP 507 EP 511 DI 10.1002/jts.21823 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 198CD UT WOS:000322898400012 PM 23893396 ER PT J AU Talbot, LS Maguen, S Epel, ES Metzler, TJ Neylan, TC AF Talbot, Lisa S. Maguen, Shira Epel, Elissa S. Metzler, Thomas J. Neylan, Thomas C. TI Posttraumatic Stress Disorder Is Associated With Emotional Eating SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ADMINISTERED PTSD SCALE; ABDOMINAL OBESITY; FOOD; SYSTEM; WOMEN AB The present study investigated the relationship between posttraumatic stress disorder (PTSD) and emotional eating in a sample of medically healthy and medication-free adults. Participants with PTSD (n= 44) and control participants free of lifetime psychiatric history (n= 49) completed a measure of emotional eating. Emotional eating is the tendency to eat or overeat in response to negative emotions. PTSD participants exhibited greater emotional eating than control participants ((2)= .20) and emotional eating increased with higher PTSD symptom severity (R-2= .11). Results supported the stress-eating-obesity model whereby emotional eating is a maladaptive response to stressors. Over time, this could lead to weight gain, particularly abdominal stores, and contribute to higher risk for comorbid medical disorders. Findings suggest the importance of future longitudinal research to understand whether emotional eating contributes to the high rates of obesity, diabetes, and heart disease in PTSD. C1 [Talbot, Lisa S.; Maguen, Shira; Metzler, Thomas J.; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Talbot, Lisa S.; Maguen, Shira; Epel, Elissa S.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Talbot, LS (reprint author), San Francisco VA Med Ctr 116H, 4150 Clement St, San Francisco, CA 94121 USA. EM lisa.talbot@gmail.com FU NIMH NIH HHS [R01 MH073978, 5R01MH073978-04, 5R34MH077667-03, R34 MH077667] NR 23 TC 19 Z9 19 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2013 VL 26 IS 4 BP 521 EP 525 DI 10.1002/jts.21824 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 198CD UT WOS:000322898400014 PM 23893425 ER PT J AU Dekel, S Mandl, C Solomon, Z AF Dekel, Sharon Mandl, Christine Solomon, Zahava TI Is the Holocaust Implicated in Posttraumatic Growth in Second-Generation Holocaust Survivors? A Prospective Study SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID TRAUMA; LEGACY AB With the growing interest in posttraumatic growth (PTG), and the ongoing debate on the implications of transgenerational transmission of trauma, this longitudinal study examined PTG among Holocaust survivor offspring following their own exposure to trauma. Using self-report questionnaires, we assessed PTG over time in middle aged (age: M = 53 years) Israeli male combat veterans of the 1973 Yom Kippur War whose parents were (n = 43) and were not (n = 156) second-generation survivors of the Nazi Holocaust at 2 time points: 30 and 35 years following the war (in 2003 and 2008). Posttraumatic stress disorder symptoms and trauma exposure were also assessed in 1991. We hypothesized that second-generation survivors would report more PTG than controls. However, repeated measures design revealed that the second-generation veterans reported less PTG than veterans who were not second generation, which was evident in the PTG domains of relations to others, personal strength, and appreciation of life. Our findings suggest that transmission of trauma from one generation to the next is possibly implicated in the offspring's propensity for growth following subsequent trauma. Future research is warranted to examine the link between transmission of trauma and positive outcomes following trauma. C1 [Dekel, Sharon; Mandl, Christine; Solomon, Zahava] Tel Aviv Univ, Bob Shapell Sch Social Work, IL-69978 Tel Aviv, Israel. RP Dekel, S (reprint author), Massachusetts Gen Hosp East, PTSD Res Lab, 120 2nd Ave, Charlestown, MA 02129 USA. EM dekel.sharon@gmail.com NR 18 TC 7 Z9 7 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2013 VL 26 IS 4 BP 530 EP 533 DI 10.1002/jts.21836 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 198CD UT WOS:000322898400016 PM 23893570 ER PT J AU Gervais, DA AF Gervais, Debra A. TI Cryoablation versus Radiofrequency Ablation for Renal Tumor Ablation: Time to Reassess? SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID RADIO-FREQUENCY ABLATION; CELL CARCINOMA; PERCUTANEOUS CRYOABLATION; ONCOLOGIC OUTCOMES; METAANALYSIS; EXPERIENCE; CANCER C1 Massachusetts Gen Hosp, Dept Radiol Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM dgervais@partners.org NR 19 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 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD AUG PY 2013 VL 24 IS 8 BP 1135 EP 1138 DI 10.1016/j.jvir.2013.05.030 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 198LL UT WOS:000322924300007 PM 23885912 ER PT J AU Sheth, RA Hesketh, R Kong, DS Wicky, S Oklu, R AF Sheth, Rahul A. Hesketh, Robin Kong, David S. Wicky, Stephan Oklu, Rahmi TI Barriers to Drug Delivery in Interventional Oncology SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID INTERSTITIAL FLUID PRESSURE; UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RANDOMIZED CONTROLLED TRIAL; RENAL-CELL CARCINOMA; SOLID TUMORS; VASCULAR NORMALIZATION; LUNG-CANCER; CHEMOEMBOLIZATION; PENETRATION; BEVACIZUMAB AB Although much attention has been paid to mechanisms of anticancer drug resistance that focus. on intracellular processes that,. protect tumor cells, it has recently become increasingly evident that the unique features of the tumor microenvironment profoundly impact the efficacy of cancer therapies. The properties of this extracellular milieu, including increased interstitial pressure, decreased pH, hypoxia, and abnormal vascularity, result in limited drug efficacy; this finding is true not only for systemic chemotherapy but also for catheter-based therapies, including chemoembolization and radioembolization. The present review summarizes the bathers to drug delivery imposed by the tumor microenvironment and provides methods' to overcome these hurdles. C1 [Sheth, Rahul A.; Wicky, Stephan; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc Imaging & Intervent, Boston, MA USA. [Kong, David S.] MIT, Lincoln Lab, Lexington, MA 02173 USA. [Hesketh, Robin] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, 55 Fruit St,Gray Bigelow 290, Boston, MA 02114 USA. EM roklu@partners.org FU Defense for Research and Engineering under Air Force Contract [FA8721-05-C-0002] FX This work was sponsored by the Assistant Secretary of Defense for Research and Engineering under Air Force Contract FA8721-05-C-0002. Opinions, interpretations, recommendations, and conclusions are those of the authors and are not necessarily endorsed by the United States Government. None of the authors have identified a conflict of interest. NR 43 TC 12 Z9 12 U1 1 U2 17 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 AUG PY 2013 VL 24 IS 8 BP 1201 EP 1207 DI 10.1016/j.jvir.2013.03.034 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 198LL UT WOS:000322924300016 PM 23735316 ER PT J AU Wardlaw, JM Smith, EE Biessels, GJ Cordonnier, C Fazekas, F Frayne, R Lindley, RI O'Brien, JT Barkhof, F Benavente, OR Black, SE Brayne, C Breteler, M Chabriat, H DeCarli, C de Leeuw, FE Doubal, F Duering, M Fox, NC Greenberg, S Hachinski, V Kilimann, I Mok, V van Oostenbrugge, R Pantoni, L Speck, O Stephan, BCM Teipel, S Viswanathan, A Werring, D Chen, C Smith, C van Buchem, M Norrving, B Gorelick, PB Dichgans, M AF Wardlaw, Joanna M. Smith, Eric E. Biessels, Geert J. Cordonnier, Charlotte Fazekas, Franz Frayne, Richard Lindley, Richard I. O'Brien, John T. Barkhof, Frederik Benavente, Oscar R. Black, Sandra E. Brayne, Carol Breteler, Monique Chabriat, Hugues DeCarli, Charles de Leeuw, Frank-Erik Doubal, Fergus Duering, Marco Fox, Nick C. Greenberg, Steven Hachinski, Vladimir Kilimann, Ingo Mok, Vincent van Oostenbrugge, Robert Pantoni, Leonardo Speck, Oliver Stephan, Blossom C. M. Teipel, Stefan Viswanathan, Anand Werring, David Chen, Christopher Smith, Colin van Buchem, Mark Norrving, Bo Gorelick, Philip B. Dichgans, Martin CA STand Reporting Vasc Changes TI Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration SO LANCET NEUROLOGY LA English DT Review ID VIRCHOW-ROBIN SPACES; WHITE-MATTER HYPERINTENSITIES; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; VASCULAR COGNITIVE IMPAIRMENT; MAGNETIC-RESONANCE IMAGES; ASSOCIATION/AMERICAN-STROKE-ASSOCIATION; SMALL SUBCORTICAL INFARCTIONS; ENLARGED PERIVASCULAR SPACES; CEREBRAL AMYLOID ANGIOPATHY; SILENT BRAIN INFARCTS AB Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for Reporting Vascular changes on nEuroimaging (STRIVE). C1 [Wardlaw, Joanna M.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Wardlaw, Joanna M.; Smith, Colin] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Doubal, Fergus] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci & Radiol, Hotchkiss Brain Inst, Calgary, AB, Canada. [Smith, Eric E.; Frayne, Richard] Univ Calgary, Seaman Family MR Res, Calgary, AB, Canada. [Biessels, Geert J.] UMC, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands. [Cordonnier, Charlotte] Lille Univ Hosp, Dept Neurol, Lille, France. [Fazekas, Franz] Graz Univ, Dept Med Neurol, Graz, Austria. [Lindley, Richard I.] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. [O'Brien, John T.] Univ Cambridge, Dept Psychiat, Addenbrookes Hosp, Cambridge, England. [Barkhof, Frederik] Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands. [Benavente, Oscar R.] Univ British Columbia, Dept Med, Div Neurol, Brain Res Ctr, Vancouver, BC, Canada. [Black, Sandra E.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Brayne, Carol] Cambridge Inst Publ Hlth, Sch Clin Med, Cambridge, England. [Breteler, Monique] German Ctr Neurodegenerat Dis, Bonn, Germany. [Chabriat, Hugues] Univ Paris 07, INSERM, Hop Lariboisiere, Serv Neurol, Paris, France. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [de Leeuw, Frank-Erik] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Duering, Marco; Dichgans, Martin] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany. [Werring, David] UCL, Inst Neurol, Dept Brain Repair & Rehabil, London, England. [Greenberg, Steven; Viswanathan, Anand] Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. [Hachinski, Vladimir] Western Univ, Dept Clin Neurol Sci, London, ON, Canada. [Kilimann, Ingo; Teipel, Stefan] German Ctr Neurodegenerat Dis DZNE Rostock Greifs, Rostock, Germany. [Mok, Vincent] Chinese Univ Hong, Div Neurol, Dept Med andTherapeut, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Mok, Vincent; van Oostenbrugge, Robert] Maastricht Univ Med Ctr, Dept Neurol, Sch Mental Hlth & Neurosci, Maastricht, Netherlands. [van Oostenbrugge, Robert] Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. [Pantoni, Leonardo] Univ Florence, Azienda Univ Osped Careggi, Dept Neurosci Pharmacol & Childs Hlth NEUROFA, Florence, Italy. [Speck, Oliver] Univ Magdeburg, Inst Expt Phys, Fac Nat Sci, Dept Biomed Magnet Resonance, D-39106 Magdeburg, Germany. [Stephan, Blossom C. M.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Chen, Christopher] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [van Buchem, Mark] Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands. [Norrving, Bo] Skane Univ Hosp, Dept Clin Sci, Neurol Sect, Lund, Sweden. [Gorelick, Philip B.] Hauenstein Neurosci Ctr, St Marys Hlth Care, Grand Rapids, MI USA. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. RP Wardlaw, JM (reprint author), Univ Edinburgh, Western Gen Hosp, Div Neuroimaging Sci, Edinburgh EH4 2XU, Midlothian, Scotland. EM joanna.wardiaw@ed.ac.uk RI Chen, Christopher/E-7023-2013; Frayne, Richard/F-9347-2012; Fox, Nick/B-1319-2009; Leeuw, H.F./L-4479-2015; Smith, Eric/C-5443-2012; Mok, Vincent /N-6421-2015; Lindley, Richard/B-8148-2013; Chabriat, Hugues/G-5699-2010; de Leeuw, Frank-Erik/E-4795-2012; OI Stephan, Blossom/0000-0002-1235-360X; Norrving, Bo/0000-0002-8024-5096; Frayne, Richard/0000-0003-0358-1210; Fox, Nick/0000-0002-6660-657X; Smith, Eric/0000-0003-3956-1668; Lindley, Richard/0000-0002-0104-5679; Chabriat, Hugues/0000-0001-8436-6074; Black, Sandra/0000-0001-7093-8289 FU Centre of Excellence in Neurodegeneration (COEN) concordat (UK Medical Research Council) [COEN017]; Centre of Excellence in Neurodegeneration (COEN) concordat (German Centre for Neurodegenerative Disease [DZNE]) [COEN017]; Centre of Excellence in Neurodegeneration (COEN) concordat (Canadian Institutes of Health Research [CIHR]) [COEN017]; Royal Society of Edinburgh; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration; UK Cross-Council Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK; Carl Friedrich von Siemens Foundation; Vascular Dementia Research Foundation; NIHR Biomedical Research Unit in Dementia; FP6 ERA-NET NEURON grant [01 EW1207]; Canadian Stroke Network FX The following institutions provided funding: the Centres of Excellence in Neurodegeneration (COEN) concordat (UK Medical Research Council, the German Centre for Neurodegenerative Disease [DZNE], and the Canadian Institutes of Health Research [CIHR]) reference COEN017; Royal Society of Edinburgh; Scottish Imaging Network, a Platform for Scientific Excellence (SINAPSE) Collaboration; UK Cross-Council Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK; Carl Friedrich von Siemens Foundation; Vascular Dementia Research Foundation; NIHR Biomedical Research Unit in Dementia awarded to Cambridge University Hospitals NHS Trust and the University of Cambridge, Cambridge, UK; NIHR Biomedical Research Unit in Dementia awarded to UCL Hospitals NHS Trust and UCL, London UK; FP6 ERA-NET NEURON grant (01 EW1207); and the Canadian Stroke Network. We thank M Henderson, K Shuler, L Thomas, I Wittko, and Anna Charlton for administrative support. NR 111 TC 502 Z9 516 U1 18 U2 134 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 AUG PY 2013 VL 12 IS 8 BP 822 EP 838 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 195GP UT WOS:000322690600020 PM 23867200 ER PT J AU DeAngelo, DJ Spencer, A Bhalla, KN Prince, HM Fischer, T Kindler, T Giles, FJ Scott, JW Parker, K Liu, A Woo, M Atadja, P Mishra, KK Ottmann, OG AF DeAngelo, D. J. Spencer, A. Bhalla, K. N. Prince, H. M. Fischer, T. Kindler, T. Giles, F. J. Scott, J. W. Parker, K. Liu, A. Woo, M. Atadja, P. Mishra, K. K. Ottmann, O. G. TI Phase Ia/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies SO LEUKEMIA LA English DT Article DE panobinostat; histone deacetylase; myelofibrosis; Hodgkin lymphoma; myelodysplastic disorders; myeloma ID HISTONE DEACETYLASE INHIBITORS; T-CELL LYMPHOMA; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; REFRACTORY MULTIPLE-MYELOMA; INTERNATIONAL-WORKING-GROUP; RESPONSE CRITERIA; HYDROXAMIC ACID; LBH589; ACETYLATION; VORINOSTAT AB Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and myeloma). In patients with leukemia and myeloid disorders, 60 mg was the MTD for weekly as well as biweekly panobinostat. In patients with lymphoma and myeloma, 40 mg was the recommended dose for phase II evaluation (formal MTD not determined) of weekly panobinostat, and 60 mg was the MTD for biweekly panobinostat. Overall, panobinostat-related grade 3-4 adverse events included thrombocytopenia (41.5%), fatigue (21%) and neutropenia (21%). Single-agent activity was observed in several indications, including Hodgkin lymphoma and myelofibrosis. This phase Ia/II study provided a broad analysis of the safety profile and efficacy of single-agent panobinostat in patients with hematologic malignancies. C1 [DeAngelo, D. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Spencer, A.] Alfred Hosp, Malignant Haematol & Stem Cell Transplantat Serv, Melbourne, Vic, Australia. [Bhalla, K. N.] Univ Kansas, Ctr Canc, Kansas City, MO USA. [Prince, H. M.] Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. [Prince, H. M.] Univ Melbourne, Melbourne, Vic, Australia. [Fischer, T.] Univ Magdeburg, Med Ctr, Dept Hematol Oncol, D-39106 Magdeburg, Germany. [Kindler, T.; Giles, F. J.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Div Hematol Oncol Pneumol, Dept Med 3, D-55122 Mainz, Germany. [Giles, F. J.] Natl Univ Ireland Univ Coll Galway, Galway, Ireland. [Giles, F. J.] Trinity Coll, Galway, Ireland. [Scott, J. W.; Parker, K.; Liu, A.; Woo, M.; Atadja, P.; Mishra, K. K.] Novartis Oncol, Florham Pk, NJ USA. [Scott, J. W.; Parker, K.; Liu, A.; Woo, M.; Atadja, P.; Mishra, K. K.; Ottmann, O. G.] Goethe Univ, Dept Hematol & Oncol, Med Klin 2, Frankfurt, Germany. RP DeAngelo, DJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Daniel_Deangelo@dfci.harvard.edu RI Kindler, Thomas/K-5995-2013; Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 FU Novartis Pharmaceuticals FX Oliver G Ottmann is an endowed professor of the German Jose Carreras Leukemia Foundation. Financial support for this study was provided by Novartis Pharmaceuticals. We thank William Fazzone, PhD, for medical editorial assistance with this manuscript and Tracy Liu, Hannah Mosca and Glen Laird for assistance with data collection and analysis. NR 54 TC 47 Z9 47 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD AUG PY 2013 VL 27 IS 8 BP 1628 EP 1636 DI 10.1038/leu.2013.38 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 197BP UT WOS:000322823200003 PM 23385375 ER PT J AU Scullen, T Santo, L Vallet, S Fulciniti, M Eda, H Cirstea, D Patel, K Nemani, N Yee, A Mahindra, A Raje, N AF Scullen, T. Santo, L. Vallet, S. Fulciniti, M. Eda, H. Cirstea, D. Patel, K. Nemani, N. Yee, A. Mahindra, A. Raje, N. TI Lenalidomide in combination with an activin A-neutralizing antibody: preclinical rationale for a novel anti-myeloma strategy SO LEUKEMIA LA English DT Article DE lenalidomide; activin A; myeloma ID REFRACTORY MULTIPLE-MYELOMA; IMMUNOMODULATORY THALIDOMIDE ANALOGS; DEPENDENT KINASE INHIBITOR; BONE-DISEASE; OSTEOBLAST DIFFERENTIATION; THERAPEUTIC APPLICATIONS; PLUS DEXAMETHASONE; CELLS; DLX5; OSTEOCLASTOGENESIS AB Given the prevalence of osteolytic bone disease in multiple myeloma (MM), novel therapies targeting bone microenvironment are essential. Previous studies have identified activin A to be of critical importance in MM-induced osteolysis. Lenalidomide is a known and approved treatment strategy for relapsed MM. Our findings demonstrate that lenalidomide acts directly on bone marrow stromal cells via an Akt-mediated increase in Jun N-terminal kinase-dependent signaling resulting in activin A secretion, with consequent inhibition of osteoblastogenesis. Here, we attempted to augment the antitumor benefits of lenalidomide while overcoming its effects on osteoblastogenesis by combining it with a neutralizing antibody to activin A. Increased activin A secretion induced by lenalidomide was abrogated by the addition of activin A-neutralizing antibody, which effectively restored osteoblast function and inhibited MM-induced osteolysis without negating the cytotoxic effects of lenalidomide on malignant cells. This provides the rationale for an ongoing clinical trial (NCT01562405) combining lenalidomide with an anti-activin A strategy. C1 [Scullen, T.; Santo, L.; Vallet, S.; Eda, H.; Cirstea, D.; Patel, K.; Nemani, N.; Yee, A.; Mahindra, A.; Raje, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Div Hematol & Oncol, Boston, MA 02114 USA. [Fulciniti, M.; Cirstea, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Div Hematol & Oncol, 55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org FU LLS; MMRF FX NR is supported by LLS and MMRF. NR 39 TC 14 Z9 14 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2013 VL 27 IS 8 BP 1715 EP 1721 DI 10.1038/leu.2013.50 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 197BP UT WOS:000322823200012 PM 23417027 ER PT J AU Bueno, M Paganetti, H Duch, MA Schuemann, J AF Bueno, M. Paganetti, H. Duch, M. A. Schuemann, J. TI An algorithm to assess the need for clinical Monte Carlo dose calculation for small proton therapy fields based on quantification of tissue heterogeneity SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; proton therapy; heterogeneities; small fields; heterogeneity index ID PENCIL BEAM ALGORITHM; BRAGG PEAK; INHOMOGENEITIES; UNCERTAINTIES; SIMULATIONS; SETTINGS; ACCURACY; TOOLKIT; CANCER; RANGE AB Purpose: In proton therapy, complex density heterogeneities within the beam path constitute a challenge to dose calculation algorithms. This might question the reliability of dose distributions predicted by treatment planning systems based on analytical dose calculation. For cases in which substantial dose errors are expected, resorting to Monte Carlo dose calculations might be essential to ensure a successful treatment outcome and therefore the benefit is worth a presumably long computation time. The aim of this study was to define an indicator for the accuracy of dose delivery based on analytical dose calculations in treatment planning systems for small proton therapy fields to identify those patients for which Monte Carlo dose calculation is warranted. Methods: Fourteen patients treated at our facility with small passively scattered proton beams (apertures diameters below 7 cm) were selected. Plans were generated in the XiO treatment planning system in combination with a pencil beam algorithm developed at the Massachusetts General Hospital and compared to Monte Carlo dose calculations. Differences in the dose to the 50% of the gross tumor volume (D50, GTV) were assessed in a field-by-field basis. A simple and fast methodology was developed to quantify the inhomogeneity of the tissue traversed by a single small proton beam using a heterogeneity index (HI)-a concept presented by Plugfelder et al. [Med. Phys. 34, 1506-1513 (2007)] for scanned proton beams. Finally, the potential correlation between the error made by the pencil beam based treatment planning algorithm for each field and the level of tissue heterogeneity traversed by the proton beam given by the HI was evaluated. Results: Discrepancies up to 5.4% were found in D50 for single fields, although dose differences were within clinical tolerance levels (<3%) when combining all of the fields involved in the treatment. The discrepancies found for each field exhibited a strong correlation to their associated HI-values (Spearman's rho = 0.8, p < 0.0001); the higher the level of tissue inhomogeneities for a particular field, the larger the error by the analytical algorithm. With the established correlation a threshold for HI can be set by choosing a tolerance level of 2-3%-commonly accepted in radiotherapy. Conclusions: The HI is a good indicator for the accuracy of proton field delivery in terms of GTV prescription dose coverage when small fields are delivered. Each HI-value was obtained from the CT image in less than 3 min on a computer with 2 GHz CPU allowing implementation of this methodology in clinical routine. For HI-values exceeding the threshold, either a change in beam direction (if feasible) or a recalculation of the dose with Monte Carlo would be highly recommended. (C) 2013 American Association of Physicists in Medicine. C1 [Bueno, M.; Duch, M. A.] Univ Politecn Cataluna, Inst Tecn Energet, Dept Dosimetria & Fis Med, E-08028 Barcelona, Spain. [Bueno, M.] Inst Bioengn Catalonia, Barcelona 08028, Spain. [Paganetti, H.; Schuemann, J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, H.; Schuemann, J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bueno, M (reprint author), Univ Politecn Cataluna, Inst Tecn Energet, Dept Dosimetria & Fis Med, E-08028 Barcelona, Spain. EM marta.bueno@upc.edu RI Duch, Maria /F-8593-2016 OI Duch, Maria /0000-0002-1560-1576 FU Institute for Bioengineering of Catalonia; Institut de Tecniques Energetiques FX The authors would like to thank Hanne Kooy, Tom Madden, and Nicolas Depauw for providing detailed information about our analytical dose calculation algorithm and for helpful discussions on proton treatment planning. The authors also thank Carles Goma for fruitful discussions on the definition of the heterogeneity index. The authors gratefully acknowledge the Monte Carlo group at MGH, especially Clemens Grassberger, for helpful comments and support throughout the development of this project. Treatment plans were made by Brian Winey. This work was supported in part by the Institute for Bioengineering of Catalonia and the Institut de Tecniques Energetiques. NR 34 TC 6 Z9 7 U1 1 U2 9 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 AUG PY 2013 VL 40 IS 8 AR 081704 DI 10.1118/1.4812682 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 195XC UT WOS:000322735900009 PM 23927301 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Calculations of two new dose metrics proposed by AAPM Task Group 111 using the measurements with standard CT dosimetry phantoms SO MEDICAL PHYSICS LA English DT Article DE computed tomography (CT); dose metric; equilibrium dose-pitch product; midpoint dose; calculation ID COMPUTED-TOMOGRAPHY; PRACTICAL APPROACH; FEASIBILITY; CTDI100; INDEX; EXAMS; MDCT AB Purpose: AAPM Task Group 111 proposed to measure the equilibrium dose-pitch product (D) over cap (eq) for scan modes involving table translation and the midpoint dose D-L(0) for stationary-table modes on the central and peripheral axes of sufficiently long (e.g., at least 40 cm) phantoms. This paper presents an alternative approach to calculate both metrics using the measurements of scanning the standard computed tomographic (CT) dosimetry phantoms on CT scanners. Methods: (D) over cap (eq) was calculated from CTDI100 and epsilon(CTDI100) (CTDI100 efficiency), and D-L(0) was calculated from (D) over cap (eq) and the approach to equilibrium function H(L) = D-L(0)/D-eq, where D-eq was the equilibrium dose. CTDI100 may be directly obtained from several sources (such as medical physicist's CT scanner performance evaluation or the IMPACT CT patient dosimetry calculator), or be derived from CTDIVol using the central to peripheral CTDI100 ratio (R-100). The authors have provided the required epsilon(CTDI100) and H(L) data in two previous papers [X. Li, D. Zhang, and B. Liu, Med. Phys. 39, 901-905 (2012); 40, 031903 (10pp.) (2013)]. R-100 was assessed for a series of GE, Siemens, Philips, and Toshiba CT scanners with multiple settings of scan field of view, tube voltage, and bowtie filter. Results: The calculated D-L(0) and D-L(0)/D-eq in PMMA and water cylinders were consistent with the measurements on two GE CT scanners (LightSpeed 16 and VCT) by Dixon and Ballard [Med. Phys. 34, 3399-3413 (2007)], the measurements on a Siemens CT scanner (SOMATOM Spirit Power) by Descamps et al. [J. Appl. Clin. Med. Phys. 13, 293-302 (2012)], and the Monte Carlo simulations by Boone [Med. Phys. 36, 4547-4554 (2009)]. Conclusions: (D) over cap (eq) and DL(0) can be calculated using the alternative approach. The authors have provided the required epsilon(CTDI100) and H(L) data in two previous papers. R-100 is presented for a majority of multidetector CT scanners currently on the market, and can be easily assessed for other CT scanners or operating conditions not covered in this study. The central to peripheral D-eq ratio is about 1.50 and 1.12 times of R-100 for the 32- and 16-cm diameter PMMA phantom, respectively. (C) 2013 American Association of Physicists in Medicine. C1 [Liu, Bob] Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Webster Ctr Adv Res & Educ Radiat, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu NR 17 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2013 VL 40 IS 8 AR 081914 DI 10.1118/1.4813899 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 195XC UT WOS:000322735900036 PM 23927328 ER PT J AU Petrick, N Sahiner, B Armato, SG Bert, A Correale, L Delsanto, S Freedman, MT Fryd, D Gur, D Hadjiiski, L Huo, ZM Jiang, YL Morra, L Paquerault, S Raykar, V Samuelson, F Summers, RM Tourassi, G Yoshida, H Zheng, B Zhou, C Chan, HP AF Petrick, Nicholas Sahiner, Berkman Armato, Samuel G., III Bert, Alberto Correale, Loredana Delsanto, Silvia Freedman, Matthew T. Fryd, David Gur, David Hadjiiski, Lubomir Huo, Zhimin Jiang, Yulei Morra, Lia Paquerault, Sophie Raykar, Vikas Samuelson, Frank Summers, Ronald M. Tourassi, Georgia Yoshida, Hiroyuki Zheng, Bin Zhou, Chuan Chan, Heang-Ping TI Evaluation of computer-aided detection and diagnosis systems SO MEDICAL PHYSICS LA English DT Article DE computer-aided detection and diagnosis (CAD); computer-aided detection (CADe); computer-aided diagnosis (CADx); performance assessment; standalone performance; reader performance; clinical performance ID OPERATING CHARACTERISTIC ANALYSIS; BREAST-CANCER DETECTION; MAXIMUM-LIKELIHOOD-ESTIMATION; IMAGE DATABASE CONSORTIUM; SMALL PULMONARY NODULES; MEMORIAL FUND LECTURE; CT COLONOGRAPHY; LUNG NODULES; SCREENING MAMMOGRAPHY; OBSERVER-PERFORMANCE AB Computer-aided detection and diagnosis (CAD) systems are increasingly being used as an aid by clinicians for detection and interpretation of diseases. Computer-aided detection systems mark regions of an image that may reveal specific abnormalities and are used to alert clinicians to these regions during image interpretation. Computer-aided diagnosis systems provide an assessment of a disease using image-based information alone or in combination with other relevant diagnostic data and are used by clinicians as a decision support in developing their diagnoses. While CAD systems are commercially available, standardized approaches for evaluating and reporting their performance have not yet been fully formalized in the literature or in a standardization effort. This deficiency has led to difficulty in the comparison of CAD devices and in understanding how the reported performance might translate into clinical practice. To address these important issues, the American Association of Physicists in Medicine (AAPM) formed the Computer Aided Detection in Diagnostic Imaging Subcommittee (CADSC), in part, to develop recommendations on approaches for assessing CAD system performance. The purpose of this paper is to convey the opinions of the AAPM CADSC members and to stimulate the development of consensus approaches and "best practices" for evaluating CAD systems. Both the assessment of a standalone CAD system and the evaluation of the impact of CAD on end-users are discussed. It is hoped that awareness of these important evaluation elements and the CADSC recommendations will lead to further development of structured guidelines for CAD performance assessment. Proper assessment of CAD system performance is expected to increase the understanding of a CAD system's effectiveness and limitations, which is expected to stimulate further research and development efforts on CAD technologies, reduce problems due to improper use, and eventually improve the utility and efficacy of CAD in clinical practice. (C) 2013 American Association of Physicists in Medicine. C1 [Petrick, Nicholas; Sahiner, Berkman; Samuelson, Frank] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Armato, Samuel G., III; Jiang, Yulei] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Bert, Alberto; Correale, Loredana; Delsanto, Silvia; Morra, Lia] im3D SpA, I-10153 Turin, Italy. [Freedman, Matthew T.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Fryd, David] Riverain Med, Miamisburg, OH 45342 USA. [Gur, David] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Hadjiiski, Lubomir; Zhou, Chuan; Chan, Heang-Ping] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Huo, Zhimin] Carestream Hlth Inc, Rochester, NY 14615 USA. [Raykar, Vikas] IBM Res, Nagawara Bangalore 560045, India. [Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Tourassi, Georgia] Oak Ridge Natl Lab, Computat Sci & Engn Div, Oak Ridge, TN 37831 USA. [Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zheng, Bin] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA. RP Chan, HP (reprint author), Univ Michigan, Dept Radiol, 1500 East Med Ctr Dr,MIB C479, Ann Arbor, MI 48109 USA. EM chanhp@umich.edu OI Bert, Alberto/0000-0001-8391-7508; Tourassi, Georgia/0000-0002-9418-9638; Zheng, Bin/0000-0002-7682-6648 FU Intramural Research Program of the National Institutes of Health, Clinical Center; University of Chicago; iCAD; Riverain Technologies through Georgetown University Medical Center FX The authors are grateful to the members and participants of the CADSC who have contributed to the stimulating discussions during many meetings and teleconferences. R. M. S. is supported in part by the Intramural Research Program of the National Institutes of Health, Clinical Center; the views expressed in this paper are the opinions of the authors and do not necessarily represent the views of the National Institutes of Health or the Department of Health and Human Services. S. G. A. and H.Y. receive royalties and licensing fees through the University of Chicago related to CAD. R. M. S. receives patent royalties and research support related to CAD from iCAD. M. T. F. receives funding from Riverain Technologies through Georgetown University Medical Center. NR 139 TC 9 Z9 10 U1 4 U2 34 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 AUG PY 2013 VL 40 IS 8 AR 087001 DI 10.1118/1.4816310 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 195XC UT WOS:000322735900073 PM 23927365 ER PT J AU Zhang, D Li, XH Gao, YM Xu, XG Liu, B AF Zhang, Da Li, Xinhua Gao, Yiming Xu, X. George Liu, Bob TI A method to acquire CT organ dose map using OSL dosimeters and ATOM anthropomorphic phantoms SO MEDICAL PHYSICS LA English DT Article DE CT; dose measurement; organ dose; OSL; ATOM phantom ID COMPUTED-TOMOGRAPHY; MONTE-CARLO; PATIENT; DEPENDENCE; PROFILES; SCANNER AB Purpose: To present the design and procedure of an experimental method for acquiring densely sampled organ dose map for CT applications, based on optically stimulated luminescence (OSL) dosimeters "nanoDots" and standard ATOM anthropomorphic phantoms; and to provide the results of applying the method-a dose data set with good statistics for the comparison with Monte Carlo simulation result in the future. Methods: A standard ATOM phantom has densely located holes (in 3 x 3 cm or 1.5 x 1.5 cm grids), which are too small (5 mm in diameter) to host many types of dosimeters, including the nanoDots. The authors modified the conventional way in which nanoDots are used, by removing the OSL disks from the holders before inserting them inside a standard ATOM phantom for dose measurements. The authors solved three technical difficulties introduced by this modification: (1) energy dependent dose calibration for raw OSL readings; (2) influence of the brief background exposure of OSL disks to dimmed room light; (3) correct pairing between the dose readings and measurement locations. The authors acquired 100 dose measurements at various positions in the phantom, which was scanned using a clinical chest protocol with both angular and z-axis tube current modulations. Results: Dose calibration was performed according to the beam qualities inside the phantom as determined from an established Monte Carlo model of the scanner. The influence of the brief exposure to dimmed room light was evaluated and deemed negligible. Pairing between the OSL readings and measurement locations was ensured by the experimental design. The organ doses measured for a routine adult chest scan protocol ranged from 9.4 to 18.8 mGy, depending on the composition, location, and surrounding anatomy of the organs. The dose distribution across different slices of the phantom strongly depended on the z-axis mA modulation. In the same slice, doses to the soft tissues other than the spinal cord demonstrated relatively small variations, with the maximum COV around 11.4%. This might be attributed to the angular mA modulation, the placement of the dosimeters, the chest cavity of the scanned region, and the size of the phantom. Doses to the spinal cord were consistently lower than those to other soft tissues. Conclusions: The method is suited for acquiring densely sampled organ dose maps, and can be used for studying dose distributions relevant to subject size, organ location, and clinical CT protocols. (C) 2013 American Association of Physicists in Medicine. C1 [Zhang, Da; Li, Xinhua; Liu, Bob] Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. [Zhang, Da; Li, Xinhua; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Webster Ctr Adv Res & Educ Radiat, Boston, MA 02114 USA. [Gao, Yiming; Xu, X. George] Rensselaer Polytech Inst, Nucl Engn Program, Troy, NY 12180 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@bics.bwh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering [R01EB015478] FX This research is sponsored in part by the National Institute of Biomedical Imaging and Bioengineering (R01EB015478). The authors want to acknowledge Dr. Dominic Crotty and Dr. Roy Nilsen of GE for providing the tube current data at each projection. The authors also want to thank Radcal Inc. for providing the thimble chamber. NR 21 TC 7 Z9 7 U1 1 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2013 VL 40 IS 8 AR 081918 DI 10.1118/1.4816299 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 195XC UT WOS:000322735900040 PM 23927332 ER PT J AU Anand, S Hasan, T Maytin, EV AF Anand, Sanjay Hasan, Tayyaba Maytin, Edward V. TI Mechanism of Differentiation-Enhanced Photodynamic Therapy for Cancer: Upregulation of Coproporphyrinogen Oxidase by C/EBP Transcription Factors SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BINDING-PROTEIN-BETA; MAMMARY EPITHELIAL-CELLS; NF-KAPPA-B; DNA-BINDING; PROTOPORPHYRIN-IX; IN-VITRO; ENDOGENOUS PROTOPORPHYRIN; AMINOLEVULINIC ACID; GENE-TRANSCRIPTION; CARCINOMA-CELLS AB The efficacy of photodynamic therapy (PDT) for epithelial cancers is increased when PDT is combined with calcitriol (Vit D), a form of differentiation therapy (DT). Here, we describe an underlying mechanism for this effect. Differentiation-promoting agents are known to upregulate CCAAT/enhancer-binding proteins (C/EBP), powerful regulators of cellular differentiation. In subcutaneous A431 tumors in mice, pretreatment with Vit D induced the expression of C/EBP beta isoforms, and of coproporphyrinogen oxidase (CPO), a heme pathway enzyme responsible for the conversion of 5-aminolevulinic acid (ALA) into protoporphyrin IX (PpIX), the principal light-absorbing molecule during PDT. To further investigate this apparent link between C/EBPs and CPO, two cell lines (MEL and LNCaP) were exposed to differentiating agents, and levels of PpIX, C/EBPs, and CPO were measured. Differentiating agents, or transfection of C/EBP expression vectors, increased C/EBP and CPO levels in parallel. Focusing on approximately 1,300 bp of upstream CPO gene promoter, we tested the ability of recombinant C/EBP alpha, C/EBP beta, C/EBP delta, and C/EBP zeta to bind to CPO gene sequences [electrophoretic mobility shift assay (EMSA) assays] and to affect transcriptional activity (luciferase assays). Multiple C/EBP consensus binding sites were identified (15 for mouse, 18 for human). Individual probes representing each site bound to C/EBPs with characteristic affinities (strong, moderate, or weak), but when sites were inactivated in the context of the native promoter, transcriptional activity was reduced nearly equally for strong or weak sites. Cooperative interactions between regularly spaced C/EBP sites seem critical for CPO transcriptional regulation by differentiation therapy. These results provide a mechanistic rationale for DT/PDT combination therapy for cancer. (C)2013 AACR. C1 [Anand, Sanjay; Maytin, Edward V.] Cleveland Clin, Dept Biomed Engn, Lerner Res Inst, Cleveland, OH 44106 USA. [Anand, Sanjay; Maytin, Edward V.] Cleveland Clin, Dept Dermatol, Cleveland, OH 44106 USA. [Hasan, Tayyaba; Maytin, Edward V.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Maytin, EV (reprint author), Cleveland Clin Fdn, Mailstop ND-20,9500 Euclid Ave, Cleveland, OH 44195 USA. EM maytine@ccf.org FU National Cancer Institute at the NIH [P01-CA84203]; Dermatology Foundation FX This work was supported by the National Cancer Institute at the NIH, P01-CA84203 (to T. Hasan and E. V. Maytin), and a grant from the Dermatology Foundation (to S. Anand). NR 50 TC 12 Z9 12 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2013 VL 12 IS 8 BP 1638 EP 1650 DI 10.1158/1535-7163.MCT-13-0047 PG 13 WC Oncology SC Oncology GA 198FU UT WOS:000322908400024 PM 23686770 ER PT J AU Li, JF Norville, JE Aach, J McCormack, M Zhang, DD Bush, J Church, GM Sheen, J AF Li, Jian-Feng Norville, Julie E. Aach, John McCormack, Matthew Zhang, Dandan Bush, Jenifer Church, George M. Sheen, Jen TI Multiplex and homologous recombination-mediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9 SO NATURE BIOTECHNOLOGY LA English DT Letter ID GENE-EXPRESSION; CRISPR; SYSTEMS; NUCLEASES; TALEN C1 [Li, Jian-Feng; McCormack, Matthew; Zhang, Dandan; Bush, Jenifer; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Li, Jian-Feng; McCormack, Matthew; Zhang, Dandan; Bush, Jenifer; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Li, Jian-Feng; Norville, Julie E.; Aach, John; McCormack, Matthew; Zhang, Dandan; Bush, Jenifer; Church, George M.; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Norville, Julie E.; Aach, John; Church, George M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. RP Li, JF (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM060493, R01 GM60493, R01 GM070567, R01 GM70567] NR 14 TC 290 Z9 332 U1 30 U2 308 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2013 VL 31 IS 8 BP 688 EP 691 DI 10.1038/nbt.2654 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 198GS UT WOS:000322911000011 PM 23929339 ER PT J AU Barzel, B Barabasi, AL AF Barzel, Baruch Barabasi, Albert-Laszlo TI Network link prediction by global silencing of indirect correlations SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE REGULATORY NETWORKS; PROTEIN INTERACTIONS; EXPRESSION PATTERNS; COMPLEX NETWORKS; DISEASE; MAP; LANDSCAPE; BIOLOGY; CELL AB Predictions of physical and functional links between cellular components are often based on correlations between experimental measurements, such as gene expression. However, correlations are affected by both direct and indirect paths, confounding our ability to identify true pairwise interactions. Here we exploit the fundamental properties of dynamical correlations in networks to develop a method to silence indirect effects. The method receives as input the observed correlations between node pairs and uses a matrix transformation to turn the correlation matrix into a highly discriminative silenced matrix, which enhances only the terms associated with direct causal links. Against empirical data for Escherichia coli regulatory interactions, the method enhanced the discriminative power of the correlations by twofold, yielding >50% predictive improvement over traditional correlation measures and 6% over mutual information. Overall this silencing method will help translate the abundant correlation data into insights about a system's interactions, with applications ranging from link prediction to inferring the dynamical mechanisms governing biological networks. C1 [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA. [Barzel, Baruch; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Barzel, Baruch] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM barabasi@gmail.com FU US National Institutes of Health (NIH), Center of Excellence of Genomic Science (CEGS) [NIH CEGS 1P50HG4233]; NIH [1U01HL108630-01]; DARPA [11645021]; DARPA Social Media in Strategic Communications project [W911NF-12-C-0028]; Network Science Collaborative Technology Alliance; US Army Research Laboratory [NS-CTA W911NF-09-02-0053]; Office of Naval Research [N000141010968]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035, BRBAA08-Per4-C-2-0033] FX We thank B. Alipanahi and B. Frey for their valuable insights, A. Sharma, F. Simini, J. Menche, S. Rabello, G. Ghoshal, Y.-Y. Liu, T. Jia, M. Posfai, C. Song, Y.-Y. Ahn, N. Blumm, D. Wang, Z. Qu, M. Schich, D. Ghiassian, S. Gil, P. Hovel, J. Gao, M. Kitsak, M. Martino, R. Sinatra, G. Tsekenis, L. Chi, B. Gabriel, Q. Jin and Y. Li for discussions, and S. S. Aleva, S. Morrison, J. De Nicolo and A. Pawling for their support. This work was supported by the US National Institutes of Health (NIH), Center of Excellence of Genomic Science (CEGS), Grant number NIH CEGS 1P50HG4233; and the NIH, award number 1U01HL108630-01; DARPA Grant Number 11645021; DARPA Social Media in Strategic Communications project under agreement number W911NF-12-C-0028; the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under agreement number NS-CTA W911NF-09-02-0053; the Office of Naval Research under agreement number N000141010968; and the Defense Threat Reduction Agency awards WMD BRBAA07-J-2-0035 and BRBAA08-Per4-C-2-0033. NR 41 TC 64 Z9 66 U1 1 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2013 VL 31 IS 8 BP 720 EP 725 DI 10.1038/nbt.2601 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 198GS UT WOS:000322911000021 PM 23851447 ER PT J AU Su, XL Arellano-Santoyo, H Portran, D Gaillard, J Vantard, M Thery, M Pellman, D AF Su, Xiaolei Arellano-Santoyo, Hugo Portran, Didier Gaillard, Jeremie Vantard, Marylin Thery, Manuel Pellman, David TI Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control SO NATURE CELL BIOLOGY LA English DT Article ID MITOTIC SPINDLE; SACCHAROMYCES-CEREVISIAE; METAPHASE SPINDLE; ANAPHASE SPINDLE; YEAST KINESIN-8; BINDING PROTEIN; CROSS-LINKS; KIF18A; MITOSIS; MOTORS AB Molecular motors play critical roles in the formation of mitotic spindles, either through controlling the stability of individual microtubules, or by crosslinking and sliding microtubule arrays. Kinesin-8 motors are best known for their regulatory roles in controlling microtubule dynamics. They contain microtubule-destabilizing activities, and restrict spindle length in a wide variety of cell types and organisms. Here, we report an antiparallel microtubule-sliding activity of the budding yeast kinesin-8, Kip3. The in vivo importance of this sliding activity was established through the identification of complementary Kip3 mutants that separate the sliding activity and microtubule-destabilizing activity. In conjunction with Cin8, a kinesin-5 family member, the sliding activity of Kip3 promotes bipolar spindle assembly and the maintenance of genome stability. We propose a slide disassemble model where the sliding and destabilizing activity of Kip3 balance during pre-anaphase. This facilitates normal spindle assembly. However, the destabilizing activity of Kip3 dominates in late anaphase, inhibiting spindle elongation and ultimately promoting spindle disassembly. C1 [Su, Xiaolei; Arellano-Santoyo, Hugo; Pellman, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Su, Xiaolei; Arellano-Santoyo, Hugo; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Su, Xiaolei; Arellano-Santoyo, Hugo; Pellman, David] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Su, Xiaolei; Arellano-Santoyo, Hugo; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Portran, Didier; Gaillard, Jeremie; Vantard, Marylin; Thery, Manuel] Univ Grenoble 1, Lab Physiol Cellulaire & Vegetale, Inst Rech Technol & Sci Vivant, CNRS,CEA,INRA,UMR5168, F-38054 Grenoble, France. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM David_Pellman@dfci.harvard.edu FU Howard Hughes Medical Institute; National Institute of Health [GM61345]; Human Frontier Scientific Program [RGY0088/201] FX We are grateful to the Reck-Peterson Laboratory at Harvard Medical School for sharing the usage of their TIRE microscope. We appreciate H. Li's help with FAGS analysis. We thank M. Gupta and R. Ohi for suggestions and comments on the manuscript. D. Penman is supported by Howard Hughes Medical Institute and a National Institute of Health grant (GM61345). M. Thery is supported by the Human Frontier Scientific Program (RGY0088/201). H. Arellano-Santoyo is an international fellow of the Howard Hughes Medical Institute. NR 47 TC 25 Z9 26 U1 0 U2 26 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 AUG PY 2013 VL 15 IS 8 BP 948 EP U400 DI 10.1038/ncb2801 PG 20 WC Cell Biology SC Cell Biology GA 193OX UT WOS:000322570900011 PM 23851487 ER PT J AU Sadasivam, S DeCaprio, JA AF Sadasivam, Subhashini DeCaprio, James A. TI The DREAM complex: master coordinator of cell cycle-dependent gene expression SO NATURE REVIEWS CANCER LA English DT Review ID MYB-MUVB/DREAM COMPLEX; TRANSCRIPTION FACTOR TRIDENT; E2F FAMILY-MEMBER; ELEGANS VULVAR INDUCTION; N-TERMINAL DOMAIN; HUMAN B-MYB; CAENORHABDITIS-ELEGANS; DROSOPHILA-MYB; S-PHASE; DNA-BINDING AB The dimerization partner, RB-like, E2F and multi-vulval class B (DREAM) complex provides a previously unsuspected unifying role in the cell cycle by directly linking p130, p107, E2F, BMYB and forkhead box protein M1. DREAM mediates gene repression during the G0 phase and coordinates periodic gene expression with peaks during the G1/S and G2/M phases. Perturbations in DREAM complex regulation shift the balance from quiescence towards proliferation and contribute to the increased mitotic gene expression levels that are frequently observed in cancers with a poor prognosis. C1 [Sadasivam, Subhashini] Natl Ctr Biol Sci TIFR, Inst Stem Cell Biol & Regenerat Med, Bangalore 560065, Karnataka, India. [DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [DeCaprio, James A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM james_decaprio@dfci.harvard.edu FU US Public Health Service [P01CA050661, R01CA63113] FX The authors gratefully acknowledge the many helpful discussions about DREAM with L. Litovchick, N. Dyson, M. Botchan and K. Engeland. This work was supported in part by US Public Health Service grants P01CA050661 and R01CA63113 to J.A.D. NR 141 TC 73 Z9 73 U1 2 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2013 VL 13 IS 8 BP 585 EP 595 DI 10.1038/nrc3556 PG 11 WC Oncology SC Oncology GA 187YS UT WOS:000322158200012 PM 23842645 ER PT J AU Pfeffer, G Horvath, R Klopstock, T Mootha, VK Suomalainen, A Koene, S Hirano, M Zeviani, M Bindoff, LA Yu-Wai-Man, P Hanna, M Carelli, V McFarland, R Majamaa, K Turnbull, DM Smeitink, J Chinnery, PF AF Pfeffer, Gerald Horvath, Rita Klopstock, Thomas Mootha, Vamsi K. Suomalainen, Anu Koene, Saskia Hirano, Michio Zeviani, Massimo Bindoff, Laurence A. Yu-Wai-Man, Patrick Hanna, Michael Carelli, Valerio McFarland, Robert Majamaa, Kari Turnbull, Douglas M. Smeitink, Jan Chinnery, Patrick F. TI New treatments for mitochondrial disease-no time to drop our standards SO NATURE REVIEWS NEUROLOGY LA English DT Article ID HEREDITARY OPTIC NEUROPATHY; PLACEBO-CONTROLLED TRIAL; CONGENITAL LACTIC-ACIDOSIS; CONTROLLED CLINICAL-TRIAL; COENZYME Q(10) TREATMENT; COMPLEX-I DEFICIENCY; SKELETAL-MUSCLE; DOUBLE-BLIND; MELAS SYNDROME; DICHLOROACETATE TREATMENT AB Mitochondrial dysfunction is a common cause of inherited multisystem disease that often involves the nervous system. Despite major advances in our understanding of the pathophysiology of mitochondrial diseases, clinical management of these conditions remains largely supportive. Using a systematic approach, we identified 1,039 publications on treatments for mitochondrial diseases, only 35 of which included observations on more than five patients. Reports of a positive outcome on the basis of a biomarker of unproven clinical significance were more common in nonrandomized and nonblinded studies, suggesting a publication bias toward positive but poorly executed studies. Although trial design is improving, there is a critical need to develop new biomarkers of mitochondrial disease. In this Perspectives article, we make recommendations for the design of future treatment trials in mitochondrial diseases. Patients and physicians should no longer rely on potentially biased data, with the associated costs and risks. C1 [Pfeffer, Gerald; Yu-Wai-Man, Patrick; McFarland, Robert; Turnbull, Douglas M.; Chinnery, Patrick F.] Newcastle Univ, Wellcome Trust Ctr Mitochondrial Res, Inst Genet Med Ageing & Hlth, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Klopstock, Thomas] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80539 Munich, Germany. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. [Suomalainen, Anu] Univ Helsinki, Dept Neurol, Cent Hosp, Helsinki, Finland. [Koene, Saskia; Smeitink, Jan] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, NL-6525 ED Nijmegen, Netherlands. [Hirano, Michio] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10027 USA. [Zeviani, Massimo] Fdn Carlo Besta Inst Neurol IRCCS, Unit Mol Neurogenet, Milan, Italy. [Bindoff, Laurence A.] Univ Bergen, IKM, Bergen, Norway. [Bindoff, Laurence A.] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway. [Hanna, Michael] UCL Inst Neurol, London, England. [Carelli, Valerio] IRCCS Ist Sci Neurol, Bologna, Italy. [Majamaa, Kari] Univ Oulu, Dept Neurol, Inst Clin Med, SF-90100 Oulu, Finland. RP Chinnery, PF (reprint author), Newcastle Univ, Wellcome Trust Ctr Mitochondrial Res, Inst Genet Med Ageing & Hlth, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. EM patrick.chinnery@ncl.ac.uk RI Zeviani, Massimo/K-2891-2014; Koene, Saskia/G-9321-2015; Smeitink, Jan/C-1351-2013; OI Koene, Saskia/0000-0002-9876-744X; CARELLI, VALERIO/0000-0003-4923-6404; Bindoff, Laurence/0000-0003-0988-276X FU Canadian Institutes of Health Research; Sigrid Juselius Foundation; Jane and Atos Erkko Foundation; DoH/HEFCE; Eurostars Programme [ESTAR 11205]; ZonMW PM Rare; Dutch Science Organisation (NWO) CSBR Program [853.00.130]; Wellcome Trust Centre for Mitochondrial Research [096919Z/11/Z]; Medical Research Council (UK) Centre for Translational Research in Neuromuscular Diseases; EU FP7 TIRCON; NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospital NHS Foundation Trust; NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospital Newcastle University; Marriott Foundation; Telethon Italy [GPP10005]; German Federal Ministry of Education and Research (BMBF) [01GM1113A]; BMBF (German Centre for Vertigo and Balance Disorders) [01E00901]; European Commission Seventh Framework Programme (FP7, HEALTH-F2-2011) [277984] FX G. Pfeffer is the recipient of a Bisby Fellowship from the Canadian Institutes of Health Research.; A. Suomalainen is supported by the Sigrid Juselius Foundation and the Jane and Atos Erkko Foundation. R. McFarland is an honorary consultant paediatric neurologist at Newcastle upon Tyne Foundation Hospitals NHS Trust and a DoH/HEFCE-funded Clinical Senior Lecturer. J. Smeitink receives additional support from the Eurostars Programme (ESTAR 11205), ZonMW PM Rare and the Dutch Science Organisation (NWO) CSBR Program (853.00.130). P. F. Chinnery is an Honorary Consultant Neurologist at Newcastle upon Tyne Foundation Hospitals NHS Trust, is a Wellcome Trust Senior Fellow in Clinical Science (084980/Z/08/Z), and a UK National Institute for Health Research (NIHR) Senior Investigator. P. F. Chinnery receives additional support from the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z), the Medical Research Council (UK) Centre for Translational Research in Neuromuscular Diseases, EU FP7 TIRCON, and the NIHR Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The support of the Marriott Foundation is gratefully acknowledged. The views expressed are those of the authors and not necessarily those of the NHS, MF, ZonMW, NOW, the NIHR or the Department of Health. M. Zeviani (GPP10005) and V. Carelli are supported by Telethon Italy. For this study, T. Klopstock acknowledges funding from the German Federal Ministry of Education and Research (BMBF, grant number 01GM1113A) for the German Network for Mitochondrial Disorders (mitoNET). T. Klopstock receives additional support from the BMBF (German Centre for Vertigo and Balance Disorders, grant number 01E00901) and from the European Commission Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984, TIRCON). NR 69 TC 63 Z9 65 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD AUG PY 2013 VL 9 IS 8 BP 474 EP 481 DI 10.1038/nrneurol.2013.129 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 196LE UT WOS:000322775900010 PM 23817350 ER PT J AU Kaiser, NC Lee, GJ Lu, PH Mather, MJ Shapira, J Jimenez, E Thompson, PM Mendez, MF AF Kaiser, Natalie C. Lee, Grace J. Lu, Po H. Mather, Michelle J. Shapira, Jill Jimenez, Elvira Thompson, Paul M. Mendez, Mario F. TI What dementia reveals about proverb interpretation and its neuroanatomical correlates SO NEUROPSYCHOLOGIA LA English DT Article DE Frontotemporal dementia; Alzheimer's disease; MRI; Tensor based morphometry; Proverbs; Executive functioning ID ONSET ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; BEHAVIORAL VARIANT; COGNITIVE DEFICITS; CLINICAL-DIAGNOSIS; RIGHT-HEMISPHERE; FRONTAL VARIANT; LANGUAGE; BRAIN; COMPREHENSION AB Objective: Neuropsychologists frequently include proverb interpretation as a measure of executive abilities. A concrete interpretation of proverbs, however, may reflect semantic impairments from anterior temporal lobes, rather than executive dysfunction from frontal lobes. The investigation of proverb interpretation among patients with different dementias with varying degrees of temporal and frontal dysfunction may clarify the underlying brain-behavior mechanisms for abstraction from proverbs. We propose that patients with behavioral variant frontotemporal dementia (bvFTD), who are characteristically more impaired on proverb interpretation than those with Alzheimer's disease (AD), are disproportionately impaired because of anterior temporal-mediated semantic deficits. Methods: Eleven patients with bvFTD and 10 with AD completed the Delis-Kaplan Executive Function System (D-KEFS) Proverbs Test and a series of neuropsychological measures of executive and semantic functions. The analysis included both raw and age-adjusted normed data for multiple choice responses on the D-KEFS Proverbs Test using independent samples t-tests. Tensor-based morphometry (TBM) applied to 3D T1-weighted MRI scans mapped the association between regional brain volume and proverb performance. Computations of mean Jacobian values within select regions of interest provided a numeric summary of regional volume, and voxel-wise regression yielded 3D statistical maps of the association between tissue volume and proverb scores. Results: The patients with bvFTD were significantly worse than those with AD in proverb interpretation. The worse performance of the bvFTD patients involved a greater number of concrete responses to common, familiar proverbs, but not to uncommon, unfamiliar ones. These concrete responses to common proverbs correlated with semantic measures, whereas concrete responses to uncommon proverbs correlated with executive functions. After controlling for dementia diagnosis, TBM analyses indicated significant correlations between impaired proverb interpretation and the anterior temporal lobe region (left > right). Conclusions: Among two dementia groups, those with bvFTD, demonstrated a greater number of concrete responses to common proverbs compared to those with AD, and this performance correlated with semantic deficits and the volume of the left anterior lobe, the hub of semantic knowledge. The findings of this study suggest that common proverb interpretation is greatly influenced by semantic dysfunction and that the use of proverbs for testing executive functions needs to include the interpretation of unfamiliar proverbs. Published by Elsevier Ltd. C1 [Kaiser, Natalie C.; Mather, Michelle J.; Shapira, Jill; Jimenez, Elvira; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Lee, Grace J.; Lu, Po H.; Shapira, Jill; Jimenez, Elvira; Thompson, Paul M.; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Kaiser, NC (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 401 Room A235, Los Angeles, CA USA. EM Natalie.Kaiser@va.gov FU National Institute of Health [R01AG034499-3]; GRECC Advanced Geriatric Fellowship Award FX Research supported by National Institute of Health Grant #R01AG034499-3 (M. Mendez PI); GRECC Advanced Geriatric Fellowship Award to N. Kaiser NR 56 TC 6 Z9 6 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD AUG PY 2013 VL 51 IS 9 BP 1726 EP 1733 DI 10.1016/j.neuropsychologia.2013.05.021 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 199TM UT WOS:000323018400008 PM 23747602 ER PT J AU Specks, U Merkel, PA Seo, P Spiera, R Langford, CA Hoffman, GS Kallenberg, CGM Clair, EWS Fessler, BJ Ding, L Viviano, L Tchao, NK Phippard, DJ Asare, AL Lim, N Ikle, D Jepson, B Brunetta, P Allen, NB Fervenza, FC Geetha, D Keogh, K Kissin, EY Monach, PA Peikert, T Stegeman, C Ytterberg, SR Mueller, M Sejismundo, LP Mieras, K Stone, JH AF Specks, Ulrich Merkel, Peter A. Seo, Philip Spiera, Robert Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. Clair, E. William St. Fessler, Barri J. Ding, Linna Viviano, Lisa Tchao, Nadia K. Phippard, Deborah J. Asare, Adam L. Lim, Noha Ikle, David Jepson, Brett Brunetta, Paul Allen, Nancy B. Fervenza, Fernando C. Geetha, Duvuru Keogh, Karina Kissin, Eugene Y. Monach, Paul A. Peikert, Tobias Stegeman, Coen Ytterberg, Steven R. Mueller, Mark Sejismundo, Lourdes P. Mieras, Kathleen Stone, John H. CA RAVE-ITN Res Grp TI Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTIBODY-ASSOCIATED VASCULITIS; ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES; WEGENERS-GRANULOMATOSIS; RANDOMIZED-TRIAL; SYSTEMIC VASCULITIDES; RENAL VASCULITIS; CELL-ACTIVATION; CYCLOPHOSPHAMIDE; MAINTENANCE; RITUXIMAB AB Background The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown. Methods In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. Results A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P=0.01) and at 12 months (P=0.009) but not at 18 months (P=0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, .) C1 [Specks, Ulrich; Fervenza, Fernando C.; Keogh, Karina; Peikert, Tobias; Ytterberg, Steven R.; Mieras, Kathleen] Mayo Clin Fdn, Rochester, MN USA. [Merkel, Peter A.; Kissin, Eugene Y.; Monach, Paul A.] Boston Univ, Med Ctr, Boston, MA USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seo, Philip; Geetha, Duvuru; Sejismundo, Lourdes P.] Johns Hopkins Univ, Baltimore, MD USA. [Ding, Linna; Viviano, Lisa; Mueller, Mark] NIAID, Bethesda, MD 20892 USA. [Tchao, Nadia K.; Phippard, Deborah J.; Asare, Adam L.; Lim, Noha] Immune Tolerance Network, Bethesda, MD USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH USA. [Kallenberg, Cees G. M.; Stegeman, Coen] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Clair, E. William St.; Allen, Nancy B.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Ikle, David; Jepson, Brett] Rho, Chapel Hill, NC USA. [Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA. [Brunetta, Paul] Genentech Inc, San Francisco, CA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org OI Carey, John/0000-0001-7292-2328; molloy, Eleanor/0000-0001-6798-2158 FU NIH [N01-AI-15416, ITN021AI]; National Institute of Allergy and Infectious Diseases; Juvenile Diabetes Research Foundation; Genentech; Biogen Idec; National Center for Research Resources (NCRR) [UL1 RR024150-01, UL1 RR025005, UL1 RR025771, NIH M01 RR00533]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [K24 AR049185, K23 AR052820, K24 AR02224]; Arthritis Foundation Investigator Award FX This research was performed as a project of the Immune Tolerance Network (NIH contract N01-AI-15416; protocol number ITN021AI), an international clinical research consortium head-quartered at the University of California, San Francisco.; Supported by the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec. At the Mayo Clinic, the trial was supported by a Clinical and Translational Science Award (CTSA) grant (UL1 RR024150-01) from the National Center for Research Resources (NCRR). At Johns Hopkins, the trial was supported by a CTSA grant (UL1 RR025005) from the NCRR and by grants (K24 AR049185, to Dr. Stone; and K23 AR052820, to Dr. Seo) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). At Boston University, the trial was supported by CTSA grants (UL1 RR025771 and NIH M01 RR00533) from the NCRR and a grant (K24 AR02224) from the NIAMS (all to Dr. Merkel) and an Arthritis Foundation Investigator Award (to Dr. Monach). NR 33 TC 180 Z9 190 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 1 PY 2013 VL 369 IS 5 BP 417 EP 427 DI 10.1056/NEJMoa1213277 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 193GQ UT WOS:000322547400008 PM 23902481 ER PT J AU Conwell, WD Josephson, SA Li, H Saint, S Janssen, WJ AF Conwell, Walter D. Josephson, S. Andrew Li, Howard Saint, Sanjay Janssen, William J. TI Weak in the Knees SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EATON MYASTHENIC SYNDROME AB A 61-year-old woman presented to her primary care physician with a 4-week history of progressive leg weakness, bilateral leg pain, and difficulty walking. The weakness was symmetric and did not fluctuate during the course of the day. Foreword In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage A 61-year-old woman presented to her primary care physician with a 4-week history of progressive bilateral leg weakness, bilateral leg pain, and difficulty walking. The weakness was symmetric, without exacerbating or ameliorating factors, and did not fluctuate during the course of the day. The patient also reported depression, anxiety, memory problems, and intermittent headaches that had begun several months earlier. She had a dry mouth but no difficulty swallowing. Previously very active, she had become homebound over a period of several months because of the leg weakness. ResponseWeakness is a common symptom and can result from dysfunction of either the central nervous system (brain or spinal cord) or the peripheral nervous system (anterior horn cell, nerve, neuromuscular junction, or muscle). Bilateral symmetric weakness of the legs can also result from problems with either the central ... C1 [Conwell, Walter D.; Li, Howard; Janssen, William J.] Univ Colorado, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Li, Howard] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Janssen, William J.] Natl Jewish Hlth, Dept Med, Div Pulm Med, Denver, CO 80206 USA. [Josephson, S. Andrew] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Saint, Sanjay] Univ Michigan, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI 48109 USA. [Saint, Sanjay] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Janssen, WJ (reprint author), Natl Jewish Hlth, 1400 Jackson St, Denver, CO 80206 USA. EM janssenw@njhealth.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 1 PY 2013 VL 369 IS 5 BP 459 EP 464 DI 10.1056/NEJMcps1210293 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 193GQ UT WOS:000322547400013 PM 23902486 ER PT J AU Schumacher, HR Pullman-Mooar, S Gupta, SR Dinnella, JE Kim, R McHugh, MP AF Schumacher, H. R. Pullman-Mooar, S. Gupta, S. R. Dinnella, J. E. Kim, R. McHugh, M. P. TI Randomized double-blind crossover study of the efficacy of a tart cherry juice blend in treatment of osteoarthritis (OA) of the knee SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE WOMAC; C-reactive protein; Inflammation; Placebo ID CONTROLLED-TRIAL; CLINICAL-TRIAL; PLACEBO; PAIN; ANTHOCYANINS; INFLAMMATION; CONSUMPTION; HIP; METHYLSULFONYLMETHANE; GLUCOSAMINE AB Objective: To assess the efficacy of tart cherry juice in treating pain and other features of knee osteoarthritis (OA). Methods: 58 non-diabetic patients with Kellgren grade 2-3 OA were randomized to begin treatment with cherry juice or placebo. Two 8 oz bottles of tart cherry juice or placebo were consumed daily for 6 weeks with a 1 week washout period before switching treatments (crossover design). Western Ontario McMaster Osteoarthritis Index (WOMAC) scores and walking times were recorded prior to and after each treatment period. Additionally, plasma urate, creatinine and high sensitivity C-reactive protein (hsCRP) were recorded at baseline, after the first treatment period and after the second treatment period. Acetaminophen was allowed as a rescue drug and self reported after each treatment period. Treatment effect was examined with repeated measures analysis of variance (ANOVA) using an intention-to-treat (ITT) analysis. Results: There were five withdrawals during the cherry juice treatment (four adverse events (AEs)) and seven withdrawals during the placebo treatment (three AEs). WOMAC scores decreased significantly (P < 0.01) after the cherry juice treatment but not after the placebo treatment (P = 0.46); differences between treatments were not significant (P = 0.16). hsCRP declined during the cherry juice treatment vs placebo (P < 0.01). The decline in hsCRP was associated with WOMAC improvement (P < 0.01). Walking time, acetaminophen use, plasma urate and creatinine were unaffected by treatments. Conclusions: Tart cherry juice provided symptom relief for patients with mild to moderate knee OA, but this effect was not significantly greater than placebo. Tart cherry juice lowered hsCRP levels and this effect was associated with improved WOMAC scores. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Schumacher, H. R.; Pullman-Mooar, S.; Gupta, S. R.; Dinnella, J. E.; Kim, R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Schumacher, H. R.; Pullman-Mooar, S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kim, R.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [McHugh, M. P.] Lenox Hill Hosp, Nicholas Inst Sports Med & Athlet Trauma, New York, NY 10075 USA. RP McHugh, MP (reprint author), Lenox Hill Hosp, Nicholas Inst Sports Med & Athlet Trauma, 100 E 77 ST, New York, NY 10075 USA. EM schumacr@mail.med.upenn.edu; sally.pullman-mooar@va.gov; Smita.Gupta@uphs.upenn.edu; jdinnell@mail.med.upenn.edu; rosakim330@gmail.com; mchugh@nismat.org FU CherryPharm, Inc., Geneva, NY FX Funding and cherry juice were provided by CherryPharm, Inc., Geneva, NY. NR 38 TC 9 Z9 9 U1 1 U2 11 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 AUG PY 2013 VL 21 IS 8 BP 1035 EP 1041 DI 10.1016/j.joca.2013.05.009 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 196VU UT WOS:000322806300003 PM 23727631 ER PT J AU Blagoev, KB Shukla, K Levine, H AF Blagoev, Krastan B. Shukla, Kamal Levine, Herbert TI We need theoretical physics approaches to study living systems SO PHYSICAL BIOLOGY LA English DT Editorial Material C1 [Blagoev, Krastan B.; Shukla, Kamal] Natl Sci Fdn, Arlington, VA 22230 USA. [Blagoev, Krastan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Blagoev, Krastan B.] Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Levine, Herbert] Rice Univ, Dept Bioengn, Houston, TX 77030 USA. RP Blagoev, KB (reprint author), Natl Sci Fdn, 4201 Wilson Blvd, Arlington, VA 22230 USA. EM herbert.levine@rice.edu RI Levine, Herbert/C-1704-2008 OI Levine, Herbert/0000-0002-8819-9055 NR 2 TC 0 Z9 0 U1 0 U2 24 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD AUG PY 2013 VL 10 IS 4 AR 040201 DI 10.1088/1478-3975/10/4/040201 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 195KM UT WOS:000322701100001 PM 23883648 ER PT J AU Goodman, JD McKay, JR DePhilippis, D AF Goodman, Jessica D. McKay, James R. DePhilippis, Dominick TI Progress Monitoring in Mental Health and Addiction Treatment: A Means of Improving Care SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE psychotherapy outcome; progress monitoring; outcome monitoring; substance abuse services; research synthesis ID TREATMENT OUTCOME PACKAGE; CLINICAL SUPPORT TOOLS; PSYCHOMETRIC PROPERTIES; CLIENT FEEDBACK; CONTINUING CARE; COCAINE DEPENDENCE; 24-MONTH OUTCOMES; BRIEF INSTRUMENT; STEPPED-CARE; CORE-OM AB Although monitoring of treatment response is standard practice for many medical conditions, practitioners in mental health treatments, and substance abuse treatment in particular, have been slow to adopt these practices. Progress monitoring (PM), consisting of measurement and feedback, has the potential to significantly improve treatment outcomes. This paper reviews the existing literature on the effects of PM in mental health and substance use disorder (SUD) treatment. Whereas previous reviews have examined aspects of PM in mental health treatment, this is the first such review to cover monitoring efforts in substance abuse treatment, conceptualized here as diverse forms of measurement-based care. To address drug use, monitoring in SUD treatment has typically relied on treatment attendance and urine screens as indicators of treatment progress. However, some research has shown that other means of PM can significantly improve SUD treatment effectiveness. Previous meta-analyses show that PM significantly improves outcomes in mental health treatment. More extensive research on three particular measures, demonstrate the effectiveness of PM in mental health treatment. With the growing focus on quality improvement in medical care, there is need for further research and adoption of progress monitoring methods in mental health and SUD treatment. C1 [Goodman, Jessica D.; McKay, James R.; DePhilippis, Dominick] Philadelphia Vet Affairs Med Ctr, CESATE, Philadelphia, PA USA. [DePhilippis, Dominick] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP McKay, JR (reprint author), Univ Penn, Ctr Continuum Care, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM jimrache@mail.med.upenn.edu NR 78 TC 11 Z9 11 U1 4 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD AUG PY 2013 VL 44 IS 4 BP 231 EP 246 DI 10.1037/a0032605 PG 16 WC Psychology, Multidisciplinary SC Psychology GA 198GI UT WOS:000322909900006 ER PT J AU Kessler, RC Calabrese, JR Farley, PA Gruber, MJ Jewell, MA Katon, W Keck, PE Nierenberg, AA Sampson, NA Shear, MK Shillington, AC Stein, MB Thase, ME Wittchen, HU AF Kessler, R. C. Calabrese, J. R. Farley, P. A. Gruber, M. J. Jewell, M. A. Katon, W. Keck, P. E., Jr. Nierenberg, A. A. Sampson, N. A. Shear, M. K. Shillington, A. C. Stein, M. B. Thase, M. E. Wittchen, H. -U. TI Composite International Diagnostic Interview screening scales for DSM-IV anxiety and mood disorders SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Bipolar disorder; Composite International Diagnostic Interview (CIDI); generalized anxiety disorder; major depression; panic disorder; screening scales; validity ID PATIENT HEALTH QUESTIONNAIRE; COMMON MENTAL-DISORDERS; COMORBIDITY SURVEY REPLICATION; PRIMARY-CARE PATIENTS; GENERALIZED ANXIETY; BIPOLAR DISORDER; PANIC DISORDER; DEPRESSION SCALE; HOSPITAL ANXIETY; CES-D AB Background. Lack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community epidemiological surveys throughout the world, were developed to address this problem. Method. Expert reviews and cognitive interviews generated CIDI screening scale (CIDI-SC) item pools for 30-day DSM-IV-TR major depressive episode (MDE), generalized anxiety disorder (GAD), panic disorder (PD) and bipolar disorder (BPD). These items were administered to 3058 unselected patients in 29 US primary care offices. Blinded SCID clinical reinterviews were administered to 206 of these patients, oversampling screened positives. Results. Stepwise regression selected optimal screening items to predict clinical diagnoses. Excellent concordance [area under the receiver operating characteristic curve (AUC)] was found between continuous CIDI-SC and DSM-IV/SCID diagnoses of 30-day MDE (0.93), GAD (0.88), PD (0.90) and BPD (0.97), with only 9-38 questions needed to administer all scales. CIDI-SC versus SCID prevalence differences are insignificant at the optimal CIDI-SC diagnostic thresholds (x(1)(2) = 0.0-2.9, p=0.09-0.94). Individual-level diagnostic concordance at these thresholds is substantial (AUC 0.81-0.86, sensitivity 68.0-80.2%, specificity 90.1-98.8 %). Likelihood ratio positive (LR+) exceeds 10 and LR-is 0.1 or less at informative thresholds for all diagnoses. Conclusions. CIDI-SC operating characteristics are equivalent (MDE, GAD) or superior (PD, BPD) to those of the best alternative screening scales. CIDI-SC results can be compared directly to general population CIDI survey results or used to target and streamline second-stage CIDIs. C1 [Kessler, R. C.; Gruber, M. J.; Sampson, N. A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Calabrese, J. R.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Psychiat, Cleveland, OH 44106 USA. [Farley, P. A.; Jewell, M. A.; Shillington, A. C.] EPI Q Inc, Clin Serv, Oak Brook Terrace, IL USA. [Katon, W.] Univ Washington, Sch Med, Seattle, WA USA. [Keck, P. E., Jr.] Univ Cincinnati, Coll Med, Lindner Ctr HOPE, Cincinnati, OH USA. [Keck, P. E., Jr.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. [Nierenberg, A. A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, A. A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, A. A.] Harvard Univ, Sch Med, Boston, MA USA. [Shear, M. K.] Columbia Univ, Sch Social Work, New York, NY USA. [Stein, M. B.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Thase, M. E.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, M. E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Thase, M. E.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Thase, M. E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Wittchen, H. -U.] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01062 Dresden, Germany. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM Kessler@hcp.med.harvard.edu RI Wittchen, Hans-Ulrich/A-8507-2014; OI Wittchen, Hans-Ulrich/0000-0002-6311-7711 FU AstraZeneca FX Support for this study was provided by AstraZeneca. The sponsor had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. NR 80 TC 20 Z9 20 U1 7 U2 32 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2013 VL 43 IS 8 BP 1625 EP 1637 DI 10.1017/S0033291712002334 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 187MJ UT WOS:000322122900005 PM 23075829 ER PT J AU Zhang, XY Chen, DC Xiu, MH Haile, CN He, SC Luo, X Zuo, L Rosenheck, R Kosten, TA Kosten, TR AF Zhang, X. Y. Chen, D. C. Xiu, M. H. Haile, C. N. He, S. C. Luo, X. Zuo, L. Rosenheck, R. Kosten, T. A. Kosten, T. R. TI Cigarette smoking, psychopathology and cognitive function in first-episode drug-naive patients with schizophrenia: a case-control study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Cognition; first episode; nicotine; psychopathology; schizophrenia; smoking ID NICOTINIC ACETYLCHOLINE-RECEPTOR; TOBACCO SMOKING; WORKING-MEMORY; PSYCHOSIS; DEPENDENCE; DEFICITS; ONSET; METAANALYSIS; ASSOCIATION; ABSTINENCE AB Background. Although patients with chronic schizophrenia have substantially higher smoking rates than either the general population or patients with other mental illnesses, drug-naive patients with a first episode of schizophrenia have received little systemic study. This study examined smoking rates, the association between smoking and symptom severity and cognitive function in Chinese first-episode schizophrenia (FES) patients using cross-sectional and case-control designs. Method. Two hundred and forty-four drug-naive FES patients and 256 healthy controls matched for gender, age and education completed the Fagerstrom Test for Nicotine Dependence (FTND) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients were also rated on the Positive and Negative Symptom Scale (PANSS). Results. The rate and quantity of smoking were not significantly higher among FES patients compared to the general population. Among patients, smokers scored higher than non-smokers on the total PANSS and the positive symptom subscale scores. There were no significant associations between cognitive function and smoking in either FES patients or healthy controls. Conclusions. In contrast to studies in patients with chronic schizophrenia, drug-naive FES patients did not smoke more frequently than the general population. Furthermore, patients with psychotic disorders who smoked did not exhibit significant cognitive differences compared with those who did not smoke. However, smoking may have other detrimental effects on physical and mental health, for example on positive symptoms. C1 [Zhang, X. Y.; Haile, C. N.; Kosten, T. A.; Kosten, T. R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, X. Y.; Haile, C. N.; Kosten, T. A.; Kosten, T. R.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Zhang, X. Y.; Chen, D. C.; Xiu, M. H.] Peking Univ, Beijing HuiLongGuan Hosp, Psychiat Res Ctr, Beijing 100871, Peoples R China. [He, S. C.] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. [Luo, X.; Zuo, L.; Rosenheck, R.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu OI Haile, Colin/0000-0001-8293-7291 FU National Natural Science Foundation of China [81000509]; Beijing Municipal Excellent Talents Foundation [2010 D003034000032]; United States National Institute of Health [U01-MH79639, K05-DA0454, P50-DA18827]; Stanley Medical Research Institute [03T-459, 05T-726] FX This study was funded by the National Natural Science Foundation of China (81000509), the Beijing Municipal Excellent Talents Foundation (2010 D003034000032), the United States National Institute of Health (U01-MH79639, K05-DA0454 and P50-DA18827) and the Stanley Medical Research Institute (03T-459 and 05T-726). NR 52 TC 8 Z9 9 U1 1 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2013 VL 43 IS 8 BP 1651 EP 1660 DI 10.1017/S0033291712002590 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 187MJ UT WOS:000322122900007 PM 23149169 ER PT J AU Taylor, MJ Charman, T Robinson, EB Plomin, R Happe, F Asherson, P Ronald, A AF Taylor, M. J. Charman, T. Robinson, E. B. Plomin, R. Happe, F. Asherson, P. Ronald, A. TI Developmental associations between traits of autism spectrum disorder and attention deficit hyperactivity disorder: a genetically informative, longitudinal twin study SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Attention deficit hyperactivity disorder; autism; longitudinal; twin study ID CAST CHILDHOOD ASPERGER; DEFICIT/HYPERACTIVITY DISORDER; FAMILIAL TRAIT; COMMUNITY TWIN; ADHD BEHAVIORS; SYMPTOMS; CHILDREN; SAMPLE; POPULATION; LANGUAGE AB Background. Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and associated subclinical traits, regularly co-occur with one another. However, the aetiology of their co-occurrence remains poorly understood. This paper provides the first genetically informative, longitudinal analysis of the interaction between traits of ASD and ADHD, and explores their genetic and environmental overlap. Method. Parents of approximately 5000 twin pairs completed questionnaires assessing traits of ASD and ADHD when twins were aged 8 and 12 years. Cross-lagged longitudinal modelling explored their developmental association, enabling a consideration of phenotypic-driven processes. Overlapping aetiological influences on traits at age 12 years were explored using bivariate twin modelling. Results. Traits of ADHD at age 8 years were more strongly predictive of traits of ASD at 12 years than traits of ASD at 8 years were of traits of ADHD at 12 years. Analysis of traits by subscales assessing specific symptom domains suggested that communication difficulties were most strongly associated with traits of ADHD. Bivariate modelling suggested moderate genetic overlap on traits in males (genetic correlation=0.41), and a modest degree of overlap in females (genetic correlation=0.23) at age 12 years. Conclusions. Traits of ADHD at age 8 years significantly influence traits of ASD at age 12 years, after controlling for their initial relationship at age 8 years. In particular, early ADHD traits influenced later communication difficulties. These findings demonstrate the dynamic nature of co-occurring traits across development. In addition, these findings add to a growing body of literature suggesting that traits of ASD and ADHD may arise via similar aetiological processes. C1 [Taylor, M. J.] Univ London, Ctr Res Autism & Educ, Inst Educ, Dept Psychol & Human Dev, London WC1H 0AA, England. [Charman, T.] Kings Coll London, Inst Psychiat, Dept Psychol, London, England. [Robinson, E. B.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA USA. [Plomin, R.; Happe, F.; Asherson, P.] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, London, England. [Ronald, A.] Univ London, Birkbeck Coll, Ctr Brain & Cognit Dev, Dept Psychol Sci,Genes Environm Lifespan Lab, London, England. RP Taylor, MJ (reprint author), Univ London, Ctr Res Autism & Educ, Inst Educ, Dept Psychol & Human Dev, 25 Woburn Sq, London WC1H 0AA, England. EM M.Taylor@ioe.ac.uk RI Charman, Tony/A-2085-2014; Ronald, Angelica/C-7812-2009; Taylor, Mark/D-4853-2017; OI Charman, Tony/0000-0003-1993-6549; Ronald, Angelica/0000-0002-9576-2176; Taylor, Mark/0000-0001-5161-4182; Robinson, Elise/0000-0003-2314-2792; Plomin, Robert/0000-0002-0756-3629; Happe, Francesca/0000-0001-9226-4000 FU UK Medical Research Council [G0500079]; UK Medical Research Council; Economic and Social Research Council; Clothworkers' Foundation; Pears Foundation FX The authors thank all the families who participated in the Twins Early Development Study (TEDS). TEDS is funded by a grant from the UK Medical Research Council (no. G0500079). The first author was funded by an Interdisciplinary Doctoral Studentship from the UK Medical Research Council and the Economic and Social Research Council. Research at the Centre for Research in Autism and Education is supported by the Clothworkers' Foundation and Pears Foundation. NR 44 TC 13 Z9 13 U1 3 U2 24 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2013 VL 43 IS 8 BP 1735 EP 1746 DI 10.1017/S003329171200253X PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 187MJ UT WOS:000322122900015 PM 23158218 ER PT J AU Aversa, LH Stoddard, JA Doran, NM Au, S Chow, B McFall, M Saxon, AJ Baker, DG AF Aversa, Laura H. Stoddard, Jill A. Doran, Neal M. Au, Selwyn Chow, Bruce McFall, Miles Saxon, Andrew J. Baker, Dewleen G. TI Longitudinal analysis of the relationship between PTSD symptom clusters, cigarette use, and physical health-related quality of life SO QUALITY OF LIFE RESEARCH LA English DT Article DE Health-related quality of life; PTSD; Smoking; Tobacco; SF-36; Longitudinal ID POSTTRAUMATIC-STRESS-DISORDER; SMOKING-CESSATION; ANXIETY DISORDERS; MAJOR DEPRESSION; VIETNAM VETERANS; CONTROLLED-TRIAL; MORTALITY; PREDICTOR; DISEASE; RISK AB Posttraumatic stress disorder (PTSD) symptoms, particularly numbing and hyperarousal symptoms, are related to poor physical health-related quality of life (HRQoL). Tobacco dependence is also associated with poor HRQoL, and individuals with PTSD may smoke at higher rates than the general population. Our study aimed to examine the impact of quitting smoking and changes in PTSD symptoms over time on changes in physical HRQoL. The study used archival data from enrollees (N = 943) in a smoking cessation clinical trial for veterans with PTSD (VA Cooperative study #519). Two of the physical HRQoL domains were sensitive to changes in PTSD symptoms over time: General Health and Vitality. Our findings suggest that particular physical HRQoL domains may be subject to improvement if PTSD symptoms decrease over time. C1 [Aversa, Laura H.; Baker, Dewleen G.] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. [Aversa, Laura H.; Stoddard, Jill A.] Alliant Int Univ, Calif Sch Profess Psychol, San Diego, CA USA. [Doran, Neal M.; Baker, Dewleen G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Au, Selwyn; Chow, Bruce] Vet Affairs Palo Alto Hlth Care Syst, Cooperat Studies Program, Mountain View, CA USA. [McFall, Miles; Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [McFall, Miles; Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Baker, Dewleen G.] Vet Affairs Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. RP Aversa, LH (reprint author), Vet Affairs San Diego Healthcare Syst, 3350 La Jolla Village Dr 151, San Diego, CA 92161 USA. EM laura.h.aversa@gmail.com FU Cooperative Studies Program of the Clinical Science Research and Development Service, U.S. Department of Veterans Affairs (DVA; CSP) [519, NCT00118534]; Tobacco-Related Disease Research Program [19DT-0003]; Department of Defense [CDMRP PTO 090738]; DVA [HSRD SDR09-128]; VA Center of Excellence for Stress and Mental Health; VA Merit [821]; NIAAA [1 P20 AA017839-01]; NIDA [5 U10 DA013714-08]; VA HSRD [1 IO1 HX000616-01]; Department of Defense (Navy BUMED) FX Funding was provided by the Cooperative Studies Program of the Clinical Science Research and Development Service, U.S. Department of Veterans Affairs (DVA; CSP #519, NCT00118534) and the Tobacco-Related Disease Research Program 19DT-0003. Dr. Baker receives research support from the Department of Defense (Navy BUMED and CDMRP PTO 090738) and the DVA (HSR&D SDR09-128) and is supported in part by the VA Center of Excellence for Stress and Mental Health. Dr. McFall receives research support from VA Merit #821 and DVA. Dr. Saxon receives research support from NIAAA (1 P20 AA017839-01), NIDA (5 U10 DA013714-08), and from VA HSR&D (1 IO1 HX000616-01). The views expressed herein are those of the authors and not necessarily those of the U.S. Department of Veterans Affairs. The authors report no financial relationships with commercial interests. NR 55 TC 3 Z9 3 U1 3 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD AUG PY 2013 VL 22 IS 6 BP 1381 EP 1389 DI 10.1007/s11136-012-0280-x PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 195XA UT WOS:000322735700023 PM 23054494 ER PT J AU Rodday, AM Terrin, N Chang, G Parsons, SK AF Rodday, Angie Mae Terrin, Norma Chang, Grace Parsons, Susan K. TI Performance of the parent emotional functioning (PREMO) screener in parents of children undergoing hematopoietic stem cell transplantation SO QUALITY OF LIFE RESEARCH LA English DT Article DE Quality of life; Hematopoietic stem cell transplantation; ROC analysis; Pediatric ID DEPRESSION; ANXIETY; MOTHERS; CANCER; SUBTHRESHOLD; PERSPECTIVES; COMORBIDITY; IMPAIRMENT; PREVALENCE; INVENTORY AB Parents of children undergoing hematopoietic stem cell transplantation (HSCT) may face emotional distress while managing intense treatments with uncertain outcomes. We evaluated a brief parental emotional functioning (PREMO) screener from a health-related quality of life instrument to identify parental emotional distress, as measured by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). As part of a longitudinal pediatric HSCT study, parents (N = 165) completed the Child Health Ratings Inventories, which contain the 7-item PREMO screener. Some parents (n = 117) also completed SCID modules for Anxiety, Mood, and Adjustment disorders at baseline and/or 12 months. A composite outcome was created for threshold or subthreshold levels of any of these disorders. Receiver operating characteristic (ROC) analysis assessed how the PREMO screener predicted emotional distress as measured by the SCID. A prediction model was then built. Fifty-two percent of parents completing the SCID had an Axis I disorder at baseline, while 41 % had an Axis I disorder at 12 months. The area under the ROC curve was 0.75 for the PREMO screener and 0.81 for the prediction model. The PREMO screener may identify parents with, or at risk for, emotional distress and facilitate further evaluation and intervention. C1 [Rodday, Angie Mae; Terrin, Norma; Parsons, Susan K.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Terrin, Norma; Parsons, Susan K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Chang, Grace] VA Boston Healthcare Syst, Brockton, MA USA. [Chang, Grace] Harvard Univ, Sch Med, Boston, MA USA. RP Parsons, SK (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, 800 Washington St,345, Boston, MA 02111 USA. EM sparsons@tuftsmedicalcenter.org FU American Cancer Society [PB02-186-01-PBP]; National Cancer Institute [R01 CA 119196] FX We would like to thank Sara Ratichek, MA, for her comments on earlier drafts. This study was supported in part by American Cancer Society, Research Scholars Grant PB02-186-01-PBP (SKP), and the National Cancer Institute, R01 CA 119196 (SKP). NR 21 TC 3 Z9 3 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD AUG PY 2013 VL 22 IS 6 BP 1427 EP 1433 DI 10.1007/s11136-012-0240-5 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 195XA UT WOS:000322735700027 PM 22836377 ER PT J AU Eikermann-Haerter, K Negro, A Ayata, C AF Eikermann-Haerter, Katharina Negro, Andrea Ayata, Cenk TI Spreading depression and the clinical correlates of migraine SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE animal models; aura; familial hemiplegic migraine; spreading depression; symptomatology ID FAMILIAL HEMIPLEGIC MIGRAINE; CACNA1A GENE MUTATION; CALCIUM-CHANNEL GENE; IDIOPATHIC GENERALIZED EPILEPSY; MINOR HEAD TRAUMA; FUNCTIONAL DECORTICATION; CONSUMMATORY BEHAVIOR; CLASSIC MIGRAINE; CEREBRAL-CORTEX; VISUAL-CORTEX AB Migraine is the most common neurologic condition. One-third of migraineurs experience transient neurologic symptoms, the so-called aura. There is strong evidence that spreading depression (SD) is the electro-physiologic substrate of migraine aura. SD is an intense pan-depolarization wave that slowly propagates in gray matter by way of contiguity and transiently disrupts neuronal function. When induced subcortically, striatal SD causes hemiparesis, hippocampal SD can trigger seizures and impact cognition, and bilateral thalamic SD can diminish consciousness. Recent data show that transgenic mice expressing familial hemiplegic migraine (FHM) type 1 mutations in voltage-gated Ca2+ channels (Ca(v)2.1) develop mutation-specific aura-like signs after a cortical SD similar to patients with the respective mutation. These signs are associated with facilitated subcortical SD propagation. As in FHM, mice with the R192Q mutation develop pure hemiplegia associated with cortical SDs propagating into caudoputamen. S218L mice display additional signs such as seizures and coma when SD propagates into hippocampus and thalamus. In hyperexcitable FHM brains, SD may propagate between cortex and subcortical structures via permissive gray matter bridges, or originate de novo in subcortical structures, to explain unusual and severe aura signs and symptoms. Reciprocal spread and reverberating waves can explain protracted attacks. C1 [Eikermann-Haerter, Katharina; Negro, Andrea; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA 02129 USA. RP Eikermann-Haerter, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. EM khaerter@partners.org NR 123 TC 13 Z9 13 U1 0 U2 10 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-1763 EI 1607-8470 J9 REV NEUROSCIENCE JI Rev. Neurosci. PD AUG PY 2013 VL 24 IS 4 BP 353 EP 363 DI 10.1515/revneuro-2013-0005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 199CR UT WOS:000322972500001 PM 23907418 ER PT J AU Thompson, BT Moss, M AF Thompson, B. Taylor Moss, Marc TI A New Definition for the Acute Respiratory Distress Syndrome SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE acute respiratory distress syndrome (ARDS); acute lung injury (ALI); diffuse alveolar damage (DAD); noncardiac pulmonary edema ID ACUTE LUNG INJURY; INTEROBSERVER VARIATION; PROTECTIVE VENTILATION; CLINICAL-TRIAL; ARDS; RISK; CONSENSUS; SEVERITY; ACCURACY; OUTCOMES AB Similar to other syndromes, patients are defined as having acute respiratory distress syndrome (ARDS) when they meet prespecified diagnostic criteria. These criteria have evolved over time, having gained and lost complexity, but the core principles have remained remarkably similar over the past 45 years. The specific diagnostic criteria allow clinicians and investigators to reliably identify patients with the syndrome of ARDS. ARDS is a form of acute diffuse lung injury occurring in patients with a predisposing risk factor. Lung injury is characterized by inflammation leading to increased endothelial and epithelial permeability and loss of aerated lung tissue resulting in hypoxemia and bilateral radiographic opacities on chest radiography. Additional physiological derangements include increased venous admixture and physiological dead space along with decreased respiratory system compliance. The corresponding pathological findings are lung edema, inflammation, hyaline membranes, and alveolar hemorrhage (i.e., diffuse alveolar damage). This article discusses the evolution of the definition of ARDS to the new Berlin definition of ARDS proposed in 2012 and its novel iterative refinement. C1 [Thompson, B. Taylor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Moss, Marc] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA. RP Thompson, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Bulfinch 148, Boston, MA 02114 USA. EM tthompson1@partners.org NR 35 TC 9 Z9 15 U1 0 U2 11 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD AUG PY 2013 VL 34 IS 4 BP 441 EP 447 DI 10.1055/s-0033-1351162 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 198GU UT WOS:000322911200002 PM 23934713 ER PT J AU McKinlay, JB Stoeckle, J AF McKinlay, John B. Stoeckle, John TI Peter McEwan: Thanks for the memories SO SOCIAL SCIENCE & MEDICINE LA English DT Biographical-Item C1 [McKinlay, John B.; Stoeckle, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McKinlay, John B.; Stoeckle, John] Harvard Univ, Sch Med, Boston, MA USA. EM JMcKinlay@neriscience.com NR 1 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2013 VL 91 SI SI BP R1 EP R2 DI 10.1016/j.socscimed.2013.05.020 PG 2 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 197NO UT WOS:000322858100001 ER PT J AU Sillesen, M Jin, G Oklu, R Albadawi, H Imam, AM Jepsen, CH Hwabejire, JO Ostrowski, SR Johansson, PI Rasmussen, LS Alam, HB AF Sillesen, Martin Jin, Guang Oklu, Rahmi Albadawi, Hassan Imam, Ayesha M. Jepsen, Cecilie H. Hwabejire, John O. Ostrowski, Sisse R. Johansson, Par I. Rasmussen, Lars S. Alam, Hasan B. TI Fresh-frozen plasma resuscitation after traumatic brain injury and shock attenuates extracellular nucleosome levels and deoxyribonuclease 1 depletion SO SURGERY LA English DT Article ID ENDOTHELIAL GLYCOCALYX; HEMORRHAGIC-SHOCK; DNA TRAPS; HISTONES; MICE; MARKER; BLOOD; PATHOGENESIS; INFLAMMATION; DEGRADATION AB Introduction. Traumatic brain injury and shock are among the leading causes of trauma-related mortality. We have previously shown that fresh-frozen plasma (FFP) resuscitation reduces the size of brain lesion and associated swelling compared with crystalloids. We hypothesized that this, effect would be associated with an attenuation of circulating nucleosome levels, a biomarker of injury with cytotoxic potential, through reconstitution of circulating deoxyribonuclease-1 (DNAse1), an enzyme identified as critical in nucleosome clearance from the circulation. Methods. Twelve swine underwent a protocol of traumatic brain injury followed by 40% volume-controlled hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for 2 hours before they were resuscitated with normal saline (NS) or FFP Circulating levels of nucleosomes and DNAse1 were measured whereas extracellular nucleosomes were quantified on brain histology. Lesion size and brain swelling were also quantified. Results. Nucleosome levels were significantly greater in the NS group 6 hours after resuscitation (0.32 mU vs 0.15 mU, P = .030) whereas DNAse1 levels were substantially greater in the FFP group (9.82 ng/mL vs 4.54 ng/mL, P = .010). Circulating nucleosomes levels correlated with lesion size (rho = 0.79, P = .002) as well as brain swelling (rho = 0.89, P < .001) whereas DNAse1 levels correlated with brain swelling (rho = -0.61, P =.036) but not lesion size (rho = -0.47, P = .124). Brain staining revealed nucleosome extracellularization in both groups, but this appeared more frequent in the NS-resuscitated animals. Conclusion. Our results show that resuscitation with FFP attenuates circulating. nucleosome levels and prevents DNAse1 depletion. These factors may play a role in the neuroprotective effects observed during early resuscitation with FFP. C1 [Sillesen, Martin; Jin, Guang; Imam, Ayesha M.; Jepsen, Cecilie H.; Hwabejire, John O.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care,Dept S, Boston, MA USA. [Sillesen, Martin; Rasmussen, Lars S.] Copenhagen Univ Hosp, Dept Anesthesia, Ctr Head & Orthoped, Copenhagen, Denmark. [Jin, Guang; Alam, Hasan B.] Univ Ann Arbor Hosp, Dept Surg, Ann Arbor, MI USA. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA USA. [Albadawi, Hassan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA. [Ostrowski, Sisse R.; Johansson, Par I.] Copenhagen Univ Hosp, Sect Transfus Med, Copenhagen, Denmark. [Johansson, Par I.] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Houston, TX 77030 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 5331 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu RI Johansson, Par/P-9283-2015; OI Johansson, Par/0000-0001-9778-5964; Rasmussen, Lars/0000-0002-7480-3004 FU U.S. Army Medical Research Materiel Command [GRANTT00521959]; Rigshospitalet (Copenhagen University Hospital, Denmark); Tryg Foundation (Denmark) FX The study was funded by U.S. Army Medical Research Materiel Command (GRANTT00521959; to H.A.), a grant from Rigshospitalet (Copenhagen University Hospital, Denmark; to M.S.), and L.S.R. has received a grant from the Tryg Foundation (Denmark). NR 29 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 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2013 VL 154 IS 2 BP 197 EP 205 DI 10.1016/j.surg.2013.04.002 PG 9 WC Surgery SC Surgery GA 196UB UT WOS:000322801800008 PM 23889948 ER PT J AU Zhao, T Li, YQ Liu, BL Liu, ZC Chong, W Duan, XZ Deperalta, DK Velmahos, GC Alam, HB AF Zhao, Ting Li, Yongqing Liu, Baoling Liu, Zhengcai Chong, Wei Duan, Xiuzhen Deperalta, Danielle K. Velmahos, George C. Alam, Hasan B. TI Novel pharmacologic treatment attenuates septic shock and improves long-term survival SO SURGERY LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITORS; MOLECULAR-MECHANISMS; ANTIINFLAMMATORY PROPERTIES; INFLAMMATORY RESPONSES; RECEPTOR; SEPSIS; LPS; LYMPHOMA AB Background. We have demonstrated previously that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, improves survival in a lipopolysaccharide-induced lethal model of endotoxemia. The goal of this study was to investigate the impact of SAHA on survival in a more clinically relevant model of cecal ligation and puncture (CLP)-induced septic shock and to elucidate changes in cytokine responses and organ injury. Methods. C57BL/6J mice were subjected to CLP, and 1 hour later were given intraperitoneally either SAHA dissolved in dimethyl sulfoxide or dimethyl sulfoxide only. Survival was monitored for 10 days. In a second study, livers were harvested for evaluation of acute liver injury, and peritoneal fluid and blood samples were collected for cytokine assays. In addition, RAW264.7 and bone marrow-derived macrophages were used to assess effects of SAHA on cytokine responses. Results. SAHA-treated animals displayed a substantial improvement in survival. In addition, SAHA also attenuated cytokine levels in blood and peritoneal fluid compared with vehicle animals, as well as in culture supernatant of macrophages stimulated with bacterial components (lipopolysaccharide or Pam3CSK4). Moreover, SAHA-treated animals showed a substantial decrease in acute liver injury. Conclusion. SAHA treatment improves survival, decreases "cytokine storm," and prevents distant organ damage in a lethal septic model. C1 [Zhao, Ting; Li, Yongqing; Liu, Baoling; Liu, Zhengcai; Chong, Wei; Deperalta, Danielle K.; Velmahos, George C.; Alam, Hasan B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care,Dept S, Boston, MA USA. [Liu, Baoling; Alam, Hasan B.] Univ Michigan Hosp, Dept Surg, Ann Arbor, MI 48109 USA. [Liu, Zhengcai] Fourth Mil Med Univ, Dept Hepatobiliary Surg, Xijing Hosp, Xian 710032, Peoples R China. [Chong, Wei] China Med Univ, Hosp 1, Emergency Dept, Shenyang, Peoples R China. [Duan, Xiuzhen] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 5331 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu FU NIH [RO1 GM084127] FX Supported by a grant from NIH RO1 GM084127 to HBA. NR 26 TC 19 Z9 20 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2013 VL 154 IS 2 BP 206 EP 213 DI 10.1016/j.surg.2013.04.003 PG 8 WC Surgery SC Surgery GA 196UB UT WOS:000322801800009 PM 23889949 ER PT J AU Hwabejire, JO Jin, G Imam, AM Duggan, M Sillesen, M Deperalta, D Jepsen, CH Lu, J Li, YQ deMoya, MA Alam, HB AF Hwabejire, John O. Jin, Guang Imam, Ayesha M. Duggan, Michael Sillesen, Martin Deperalta, Danielle Jepsen, Cecilie H. Lu, Jennifer Li, Yongqing deMoya, Marc A. Alam, Hasan B. TI Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock SO SURGERY LA English DT Article ID MEMBRANE PHOSPHOLIPID DEGRADATION; PERMEABILITY TRANSITION PORE; CRITICALLY-ILL PATIENTS; OXYGEN DELIVERY; CELL-DEATH; RAT-BRAIN; K+-ATPASE; GLUTAMATE; GLYCEROL; INHIBITION AB Background. Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether this effect was owing to metabolic modulation. Methods. Yorkshire swine (n = 9) underwent a protocol of computer-controlled TBI and 40% hemorrhage and were resuscitated randomly with either fresh frozen plasma equal to the volume of shed blood (FFP; n = 4) or VPA (300 mg/kg) and FFP (FFP+VPA; n = 5). Hemodynamics, brain oxygenation, and blood glucose were monitored continuously for 6 hours after resuscitation. Cerebral microdialysis was used to measure glucose, lactate, pyruvate, glutamate, and glycerol levels at baseline, 1 and 2 hours post-shock, post-resuscitation (PR), and at 2, 4, and 6 hours PR. Brain samples from the injured side were then separated into mitochondrial and cytosolic fractions, and activity of pyruvate dehydrogenase complex (PDH) was measured using a dipstick assay kit. Results. At baseline, there was no difference in brain lactate, pyruvate, glycerol, and glutamate concentrations between the groups. At all time points, there were no differences between the groups in brain oxygenation, cerebral perfusion pressure, or blood and brain glucose concentrations. After VPA infusion (PR time point), however, there was sustained decrease in lactate (0.91 +/- 0.47 vs 2.54 +/- 0.59 mmol/L; P < .01) and pyruvate (12.80 +/- 4.89 vs 46.25 +/- 9.22; P < .001) concentrations compared with the FFP alone group, implying superior glucose utilization for ATP production. There was also a decrease in concentrations of glutamate (6.64 +/- 3.68 vs 42.25 +/- 27.07 mmol/L; P = .02) and glycerol (19.20 +/- 6.76 vs 69.75 +/- 30.07 mmol/L; P = .01), in the FFP+VPA group, signifying lesser degree of excitotoxicity and brain damage, respectively. Brain PDH activity was greater in the mitochondrial fractions (5,984 +/- 504 adjusted volume intensity [INT] X mm(2) vs 4,332 +/- 1,055 INT X mm(2); P = .04) and lower in cytosolic fractions in the FFP+VPA group (1,597 +/- 1,395 vs 4,026 +/- 1,067 INT X mm(2); P = .03), indicating better mitochondrial membrane function and enhanced mitochondrial PDH retention. Conclusion. VPA treatment attenuates perturbation of post-traumatic cerebral metabolism by mitigating mitochondrial dysfunction, and decreases glutamate-mediated excitotoxic damage. These properties could explain its effectiveness in decreasing lesion size and post-traumatic cerebral edema. C1 [Hwabejire, John O.; Jin, Guang; Imam, Ayesha M.; Duggan, Michael; Sillesen, Martin; Deperalta, Danielle; Jepsen, Cecilie H.; Lu, Jennifer; Li, Yongqing; deMoya, Marc A.; Alam, Hasan B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care,Dept S, Boston, MA USA. [Jin, Guang; Alam, Hasan B.] Univ Michigan Hosp, Dept Surg, Ann Arbor, MI 48109 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 5331 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu FU US Army Medical Research Material Command [GRANTT00521959] FX Funded by a grant from the US Army Medical Research Material Command GRANTT00521959 (to HBA). NR 39 TC 10 Z9 10 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2013 VL 154 IS 2 BP 234 EP 243 DI 10.1016/j.surg.2013.04.008 PG 10 WC Surgery SC Surgery GA 196UB UT WOS:000322801800012 PM 23889951 ER PT J AU Imam, AM Jin, G Duggan, M Sillesen, M Hwabejire, JO Jepsen, CH DePeralta, D Liu, BL Lu, J deMoya, MA Socrate, S Alam, HB AF Imam, Ayesha M. Jin, Guang Duggan, Michael Sillesen, Martin Hwabejire, John O. Jepsen, Cecilie H. DePeralta, Danielle Liu, Baoling Lu, Jennifer deMoya, Marc A. Socrate, Simona Alam, Hasan B. TI Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock SO SURGERY LA English DT Article ID SEVERE HEAD-INJURY; DIFFERENT RESUSCITATION STRATEGIES; HISTONE DEACETYLASE; FLUID RESUSCITATION; INTRACRANIAL-PRESSURE; OXYGEN DELIVERY; ORGAN FAILURE; RODENT MODEL; BLOOD-LOSS; INSULTS AB Introduction. Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert a synergistic effect. Methods. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. TBI was created through a 20-mm craniotomy using a computer-controlled cortical impactor: 15-mm cylindrical tip impactor at 4 m/s velocity, 100 ms dwell time, and 12-mm penetration depth. The TBI was synchronized with the initiation of volume-controlled hemorrhage (40 +/- 5% of total blood volume). After a 2-hour period of shock, animals were randomized to 1 of 3 resuscitation groups (n = 5 per group): (1) 0.9% saline (NS); (2) FFP; and (3) FFP and VPA 300 mg/kg (FFP+VPA). The resuscitative volume for FFP was equivalent to the shed blood, whereas NS was 3 times this volume. VPA treatment was started 1 hour after hemorrhage. Animals were monitored for 6 hours post-resuscitation. At this time the brains were harvested, sectioned into 5-mm slices, and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size (mm(3)) and brain swelling (percent change compared with the uninjured side). Results. The combined TBI+HS model resulted in a highly reproducible brain injury. Lesion size and brain swelling (mean value +/- standard error of the mean) in the FFP+VPA group (1,459 +/- 218 mm(3) and 13 +/- 1%, respectively) were less than the NS group (3,285 +/- 131 mm(3) [P < .001] and 37 +/- 2% [P < .001], respectively), and the FFP alone group (2,160 +/- 203 mm(3) [P < .05] and 22 +/- 1% [P < .001], respectively). Conclusion. In a large animal model of TBI+HS, early treatment with a combination of FFP and VPA decreases the size of brain lesion and the associated swelling. C1 [Imam, Ayesha M.; Jin, Guang; Duggan, Michael; Sillesen, Martin; Hwabejire, John O.; Jepsen, Cecilie H.; DePeralta, Danielle; Liu, Baoling; Lu, Jennifer; deMoya, Marc A.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA USA. [Socrate, Simona] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Jin, Guang; Liu, Baoling; Alam, Hasan B.] Univ Michigan Hosp, Dept Surg, Ann Arbor, MI 48109 USA. RP Alam, HB (reprint author), Univ Michigan Hosp, Taubman Ctr 5331 2920, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM alamh@med.umich.edu FU US Army Medical Research Material Command [GRANTT00521959] FX Funded by a grant from the US Army Medical Research Material Command GRANTT00521959 (to HBA). NR 47 TC 16 Z9 16 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2013 VL 154 IS 2 BP 388 EP 396 DI 10.1016/j.surg.2013.05.008 PG 9 WC Surgery SC Surgery GA 196UB UT WOS:000322801800031 PM 23889966 ER PT J AU Pretorius, E Lipinski, B Bester, J Vermeulen, N Soma, P AF Pretorius, Etheresia Lipinski, Boguslaw Bester, Janette Vermeulen, Natasha Soma, Prashilla TI Albumin Stabilizes Fibrin Fiber Ultrastructure in Low Serum Albumin Type 2 Diabetes SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE Fibrin; low albumin diabetes; scanning electron microscopy ID MELLITUS; IRON; THROMBOSIS AB Serum albumin is an essential plasma protein that serves an important function in maintaining osmotic pressure. Low levels of this protein are associated with the kidney failure and hemodialysis that are often seen in diabetic patients who are at high risk of thrombotic events. In diabetes, fibrin fiber nets are changed to form dense matted deposits (DMDs, or parafibrin). Here the authors investigate whether parafibrin is also present in diagnosed low-albumin diabetes patients and whether the addition of human albumin to plasma from low-albumin diabetes type 2 individuals may change the architecture of the fibrin nets. The authors show that the addition of albumin to plasma of low-albumin diabetes patients progressively caused the DMDs typically found in these patients to revert back to ultrastructure typically seen in healthy individuals. This disease has an extremely complicated pathophysiology and thus cannot be considered as a simple condition. This study shows that serum albumin levels may play an important role in the structure of fibrin fibrils, making them more susceptible to the fibrinolytic degradation and elimination from the circulation. C1 [Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Soma, Prashilla] Univ Pretoria, Dept Physiol, Fac Hlth Sci, ZA-0002 Pretoria, South Africa. [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag X323, ZA-0007 Arcadia, South Africa. EM resia.pretorius@up.ac.za OI Pretorius, Etheresia/0000-0002-9108-2384 NR 17 TC 7 Z9 7 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD AUG PY 2013 VL 37 IS 4 BP 254 EP 257 DI 10.3109/01913123.2013.778929 PG 4 WC Microscopy; Pathology SC Microscopy; Pathology GA 195XK UT WOS:000322736700004 PM 23672265 ER PT J AU Mousa, AY Patterson, W Abu-Halimah, S Hass, SM Alhalbouni, S Sadek, BT Nanjundappa, A Modak, A Stone, PA Emmett, M AbuRahma, AF AF Mousa, Albeir Y. Patterson, William Abu-Halimah, Shadi Hass, Stephen M. Alhalbouni, Saadi Sadek, Betro T. Nanjundappa, Aravinda Modak, Asmita Stone, Patrick A. Emmett, Mary AbuRahma, Ali F. TI Patency in Arteriovenous Grafts in Hemodialysis Patients SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE hemodialysis; renal; failure; clopidogrel; aspirin; percutaneous; patency; surgical; looped; straight; primary; secondary ID CHRONIC KIDNEY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; RENAL DATA SYSTEM; FISH-OIL RICH; VASCULAR ACCESS; WAIT TECHNIQUE; PLUS ASPIRIN; GUIDELINES; LYSE; CLOPIDOGREL AB Objective: It is difficult to maintain a working access for patients on hemodialysis. Despite current Dialysis Outcome Quality Initiatives recommendations of Fistula First, not everyone qualifies for a fistula, and those patients undergoing the alternative treatment, a graft, can experience graft failure. This study examines factors associated with arteriovenous graft (AVG) patency. Methods: A retrospective analysis was completed for all the patients who had an AVG during 2005 to 2010. Data were collected from electronic medical records, including date of first and subsequent interventions, salvage technique (surgical vs percutaneous), medical comorbidities, and use of antiplatelet medications (aspirin and clopidogrel). Continuous variables were compared with 2 sample t tests, and categorical variables with chi-square/Fisher exact test. Logistic regression was used to determine the odds ratio for risk factors associated with patency. A P value of <.05 was considered significant. All analyses were done using SAS 9.2 (SAS Institute Inc, Cary, North Carolina). Results: A total of 193 unique patients had an AVG. Of the 193 patients, 64% were female, 83% were hypertensive, and 64% were diabetic. The locations of the grafts were 80% arm, 15% forearm, and 5% thigh. Configurations, including loop and straight, were 34% and 63%, respectively. Comorbidities were not associated with patency. Primary patency was not found to be different with respect to location and configuration of graft and type of intervention. Primary patency for patients taking only aspirin (n = 43) and only clopidogrel (n = 17) were significantly different from patients on a combination of aspirin and clopidogrel (n = 7), with a P = .0051 and P = .0447, respectively. Conclusion: Neither location nor configuration affects the primary patency of AVGs. Aspirin alone is not inferior to aspirin and clopidogrel. Further prospective studies may be warranted to establish a consensus regarding medications and patency with AVGs. C1 [Mousa, Albeir Y.; Abu-Halimah, Shadi; Hass, Stephen M.; Alhalbouni, Saadi; Nanjundappa, Aravinda; Stone, Patrick A.; AbuRahma, Ali F.] Univ Virginia, Dept Surg, Robert C Byrd Hlth Sci Ctr, Charleston, WV 25304 USA. [Patterson, William; Sadek, Betro T.; Modak, Asmita; Emmett, Mary] CAMC Hlth Educ & Res Inst, Charleston, WV USA. [Modak, Asmita] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mousa, AY (reprint author), Univ Virginia, Dept Surg, Robert C Byrd Hlth Sci Ctr, 3110 MacCorkle Ave SE, Charleston, WV 25304 USA. EM amousa@hsc.wvu.edu RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 41 TC 3 Z9 3 U1 1 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD AUG PY 2013 VL 47 IS 6 BP 438 EP 443 DI 10.1177/1538574413493678 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 196JI UT WOS:000322770300005 PM 23853221 ER PT J AU Alhalbouni, S Deem, S Abu-Halimah, S Sadek, BT Mousa, A AF Alhalbouni, Saadi Deem, Samuel Abu-Halimah, Shadi Sadek, Betro T. Mousa, Albeir TI Atypical Presentation of Priapism in a Patient With Acute Iliocaval Deep Venous Thrombosis Secondary to May-Thurner Syndrome SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE priapism; DVT; IVC; iliac; thrombosis ID HIGH-FLOW PRIAPISM; MANAGEMENT; EMBOLIZATION; DIAGNOSIS AB We report on a 42-year-old male who presented with priapism, severe scrotal swelling, and left lower extremity pain and swelling. Initial management of priapism failed, and he was noted to have both cavernosal and glandular venous obstruction. Computed tomography (CT) was performed and identified extensive acute thrombosis involving the distal inferior vena cava and the left iliac veins. Pharmacomechanical thrombolysis (PMT) was started over the course of two days. At completion of thrombolysis, the culprit lesion in the left common iliac vein was treated with angioplasty and stenting. His postoperative course was uneventful, and his priapism as well as the scrotal and leg swelling improved. He was discharged home on full anticoagulation. To our knowledge, this is the first available description of this rare presentation along with a literature review of the underlying vascular etiology for priapism. C1 [Deem, Samuel] W Virginia Univ, Charleston Area Med Ctr, Dept Vasc Surg, Charleston, WV 25304 USA. [Sadek, Betro T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Alhalbouni, S (reprint author), Maimonides Hosp, 4802 10th Ave, Brooklyn, NY 11219 USA. EM saadieras@yahoo.com RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 22 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD AUG PY 2013 VL 47 IS 6 BP 488 EP 492 DI 10.1177/1538574413493680 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 196JI UT WOS:000322770300015 PM 23843289 ER PT J AU Kapadia, S Hapani, S Choueiri, TK Wu, SH AF Kapadia, Samir Hapani, Sanjaykumar Choueiri, Toni K. Wu, Shenhong TI Risk of liver toxicity with the angiogenesis inhibitor pazopanib in cancer patients SO ACTA ONCOLOGICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; SOFT-TISSUE SARCOMA; PHASE-II; INDUCED HEPATOTOXICITY; OVARIAN-CANCER; TUMOR-GROWTH; OPEN-LABEL; RECURRENT; TRIAL AB Purpose. The angiogenesis inhibitor pazopanib has been approved for the treatment of advanced renal cell cancer (RCC) and soft tissue sarcoma. Severe and fatal hepatotoxicity has been observed in its clinical studies. This analysis was conducted to determine the risk of liver toxicity by a systematic review and meta-analysis of clinical trials. Patients and methods. Databases from PubMed, Web of Science and abstracts presented at ASCO meetings up to January, 2012 were searched to identify relevant studies. Eligible studies included prospective trials of cancer patients treated with pazopanib starting at 800 mg daily. Summary incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a fixed- or random-effects model. Results. A total of 1478 patients from 10 clinical trials were included. The incidences of all-grade aspartate aminotransferase (AST), alanine transaminase (ALT), and bilirubin elevation were 39.6% (95% CI 31.2-48.6%), 41.4% (95% CI 34.1-49.0%), and 24.8% (95% CI 16.3-35.3%), respectively. The incidences of high-grade (Grade 3 and 4) AST, ALT and bilirubin elevation were 6.9% (95% CI 5.5-8.6%), 9.4% (95% CI 7.8-11.4%), and 3.4% (2.4-5.0%), respectively. In comparison with placebo, pazopanib significantly increased the risk of high-grade AST elevation (RR 6.56, 95% CI 2.04-21.07, p = 0.002) and ALT elevation (RR 4.33, 95% CI 1.88-10.0, p = 0.001). However, the risks of high-grade bilirubin elevation (RR 1.31, 95% CI 0.47-3.64) and fatal hepatotoxicity (RR 2.51, 95% CI 0.12-51.91, p = 0.55) were not significantly elevated. Conclusion. The use of pazopanib was associated with a significantly increased risk of severe non-fatal hepatotoxicity in cancer patients. C1 [Kapadia, Samir; Hapani, Sanjaykumar; Wu, Shenhong] SUNY Stony Brook, Sch Med, Dept Med, Div Hematol & Oncol, Stony Brook, NY 11794 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. RP Wu, SH (reprint author), SUNY Stony Brook, Ctr Canc, 9447 SUNY, Stony Brook, NY 11794 USA. EM shenhong.wu@stonybrookmedicine.edu NR 36 TC 12 Z9 12 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD AUG PY 2013 VL 52 IS 6 BP 1202 EP 1212 DI 10.3109/0284186X.2013.782103 PG 11 WC Oncology SC Oncology GA 194CA UT WOS:000322607400020 PM 23594201 ER PT J AU El-Rayess, HM Refaat, MM Post, MD Spitzer, TR Dey, B AF El-Rayess, Hebah M. Refaat, Marwan M. Post, Miriam D. Spitzer, Thomas R. Dey, Bimalangshu TI Chronic graft-versus-host disease with skin signs suspicious for squamous cell carcinoma SO ACTA ONCOLOGICA LA English DT Letter ID LONG-TERM SURVIVORS; TRANSPLANTATION; MANIFESTATIONS C1 [El-Rayess, Hebah M.] Univ New England, Coll Osteopath Med, Biddeford, ME USA. [Refaat, Marwan M.; Spitzer, Thomas R.; Dey, Bimalangshu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. [Post, Miriam D.] Univ Colorado, Dept Pathol, Aurora, CO USA. RP Refaat, MM (reprint author), Dept Internal Med, 55 Fruit St, Boston, MA 02114 USA. EM rifaatmarwan@hotmail.com NR 8 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD AUG PY 2013 VL 52 IS 6 BP 1213 EP 1214 DI 10.3109/0284186X.2012.734923 PG 2 WC Oncology SC Oncology GA 194CA UT WOS:000322607400021 PM 23198720 ER PT J AU Branch, AD Kang, M Hollabaugh, K Wyatt, CM Chung, RT Glesby, MJ AF Branch, Andrea D. Kang, Minhee Hollabaugh, Kimberly Wyatt, Christina M. Chung, Raymond T. Glesby, Marshall J. TI In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUSTAINED VIROLOGICAL RESPONSE; INTERFERON PLUS RIBAVIRIN; BONE-MINERAL DENSITY; STAGE LIVER-DISEASE; VITAMIN-D LEVELS; COINFECTED PATIENTS; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; SEVERE FIBROSIS AB Background: Among patients with hepatitis C virus (HCV) mono-infection, 25-hydroxyvitamin D [25(OH)D] concentrations are positively associated with a response to peg-interferon/ribavirin. Data on the relation between 25(OH)D concentrations and HCV treatment response in HIV-infected patients are limited. Objective: The objective was to determine whether baseline 25(OH)D concentrations predict virologic response in BIV/HCV co-infected patients and to examine variables associated with 25(OH)D concentrations >= 30 ng/mL. Design: Data and samples from 144 HCV genotype 1, treatment-naive patients from a completed HCV treatment trial were examined in this retrospective study. Early virologic response (EVR) was defined as >= 2 log(10) reduction in HCV RNA and/or HCV RNA <600 IU/mL at week 12 of peg-interferon/ribavirin treatment. Baseline 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Results: Compared with the non-EVR control group (n = 68), the EVR group (n = 76) was younger, had fewer cirrhotic subjects, had a higher proportion with the IL28B CC genotype, had a higher albumin concentration, and had a lower HCV viral load at baseline (P <= 0.05). The difference in baseline 25(OH)D concentrations between EVR and non-EVR patients was not statistically significant (median: 25 ng/mL compared with 20 ng/mL; P = 0.23). Similar results were found for sustained virologic response (SVR). In multivariable analysis, white and Hispanic race-ethnicity (OR: 6.26; 95% CI: 2.47, 15.88; P = 0.0001) and ritonavir use (OR: 2.68; 95% CI: 1.08, 6.65; P = 0.033) were associated with higher 25 (OH)D concentrations (>= 30 ng/mL). Conclusion: Baseline 25(OH)D concentrations did not predict EVR or SVR. Because ritonavir impairs the conversion of 25(OH)D to the active metabolite, utilization of 25(OH)D may have been impaired in subjects taking ritonavir. This trial was registered at www.clinicaltrials.gov as NCT00078403. C1 Mt Sinai Sch Med, Div Liver Dis, New York, NY 10029 USA. [Wyatt, Christina M.] Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. [Kang, Minhee; Hollabaugh, Kimberly] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Glesby, Marshall J.] Weill Cornell Med Coll, Div Infect Dis, New York, NY USA. RP Branch, AD (reprint author), Mt Sinai Sch Med, 1425 Madison Ave,Icahn 11-24, New York, NY 10029 USA. EM andrea.branch@mssm.edu FU NIH [U01AI068636, U01AI068634, DA031095, DK090317, K24 AI78884] FX Supported by the NIH (U01AI068636, U01AI068634, DA031095, DK090317, and K24 AI78884). NR 60 TC 5 Z9 5 U1 1 U2 6 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2013 VL 98 IS 2 BP 423 EP 429 DI 10.3945/ajcn.112.048785 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 189SA UT WOS:000322287400022 PM 23739141 ER PT J AU Borrero, S Zhao, X Mor, MK Schwarz, EB Good, CB Gellad, WF AF Borrero, Sonya Zhao, Xinhua Mor, Maria K. Schwarz, Eleanor B. Good, Chester B. Gellad, Walid F. TI Adherence to hormonal contraception among women veterans: differences by race/ethnicity and contraceptive supply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE adherence; contraception; female veterans; race/ethnicity; unintended pregnancy ID RANDOMIZED-CONTROLLED-TRIAL; 2002 NATIONAL-SURVEY; UNINTENDED PREGNANCY; UNITED-STATES; HEALTH-CARE; FAMILY GROWTH; PROJECT; CONTINUATION; DISPARITIES; FAILURE AB OBJECTIVE: The objective of the study was to assess the adherence to hormonal contraception (pill, patch, ring, or injectable) among women veterans and examine the relationships between race/ethnicity and the months of contraceptive supply dispensed with contraceptive adherence. STUDY DESIGN: We conducted a retrospective analysis of the Department of Veterans Affairs (VA) national databases to examine the adherence to hormonal contraception over 12 months among women aged 18-45 years who had hormonal contraceptive coverage during the first week of fiscal year 2008. We examined several adherence indicators including gaps between refills and months of contraceptive coverage. Descriptive statistics and multivariable models were used to examine the associations between race/ethnicity and contraceptive supply dispensed with adherence. RESULTS: Our cohort included 6946 women: 47% were white, 6% were Hispanic, 22% were black, and 25% were other race or had missing race information. Most women (83%) received a 3 month supply of contraception at each fill. More than 64% of women had at least 1 gap in coverage of 7 days or longer. Only 22% of women received a full 12 months of contraception without any gaps (perfect adherence). Compared with whites, Hispanics were significantly more likely to experience gaps (64% vs 70%; P = .02), and Hispanics and blacks received fewer months of contraceptive coverage (9.3 vs 8.9 and 9.0, P < .001). Compared with women receiving 3 month supplies, those receiving 1 month supplies had a higher likelihood of a gap (63% vs 72%, P < .001), fewer months of coverage (9.3 vs 6.9, P < .001), and a lower likelihood of perfect adherence (22% vs 11%, P < .001). CONCLUSION: Adherence to hormonal contraception among women veterans is poor. Efforts to improve contraceptive adherence and lower risk of unintended pregnancy are needed; dispensing more months of supply for hormonal contraception may be a promising strategy. C1 [Borrero, Sonya; Zhao, Xinhua; Mor, Maria K.; Good, Chester B.; Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Borrero, Sonya; Zhao, Xinhua; Schwarz, Eleanor B.; Good, Chester B.; Gellad, Walid F.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. [Schwarz, Eleanor B.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Good, Chester B.] Vet Affairs Ctr Medicat Safety, Hines, IL USA. RP Borrero, S (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM borrerosp@upmc.edu OI Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU Office of Research and Development, Veterans Health Administration, Department of Veterans Affairs, VISN 4 CHERP Pilot Project Award FX This study was supported by the Office of Research and Development, Veterans Health Administration, Department of Veterans Affairs, VISN 4 CHERP Pilot Project Award (principal investigator, Sonya Borrero). NR 45 TC 3 Z9 3 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2013 VL 209 IS 2 AR 103.e1 DI 10.1016/j.ajog.2013.03.024 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 194UA UT WOS:000322657000008 PM 23524170 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 2013 VL 305 IS 3 BP E315 EP E316 DI 10.1152/ajpendo.00261.2013 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 195KS UT WOS:000322701700001 PM 23673160 ER PT J AU Stephenson, EJ Lessard, SJ Rivas, DA Watt, MJ Yaspelkis, BB Koch, LG Britton, SL Hawley, JA AF Stephenson, Erin J. Lessard, Sarah J. Rivas, Donato A. Watt, Matthew J. Yaspelkis, Ben B., III Koch, Lauren G. Britton, Steven L. Hawley, John A. TI Exercise training enhances white adipose tissue metabolism in rats selectively bred for low- or high-endurance running capacity SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE white adipose tissue; exercise; metabolism; mitochondria; lipolysis ID MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION; INTRINSIC AEROBIC CAPACITY; GLUCOSE-TRANSPORT ACTIVITY; SKELETAL-MUSCLE; INSULIN-RESISTANCE; ARTIFICIAL SELECTION; GENE-EXPRESSION; FAT-METABOLISM; WHOLE-BODY; OBESE MEN AB Impaired visceral white adipose tissue (WAT) metabolism has been implicated in the pathogenesis of several lifestyle-related disease states, with diminished expression of several WAT mitochondrial genes reported in both insulin-resistant humans and rodents. We have used rat models selectively bred for low-(LCR) or high-intrinsic running capacity (HCR) that present simultaneously with divergent metabolic phenotypes to test the hypothesis that oxidative enzyme expression is reduced in epididymal WAT from LCR animals. Based on this assumption, we further hypothesized that short-term exercise training (6 wk of treadmill running) would ameliorate this deficit. Approximately 22-wk-old rats (generation 22) were studied. In untrained rats, the abundance of mitochondrial respiratory complexes I-V, citrate synthase (CS), and PGC-1 was similar for both phenotypes, although CS activity was greater than 50% in HCR (P = 0.09). Exercise training increased CS activity in both phenotypes but did not alter mitochondrial protein content. Training increased the expression and phosphorylation of proteins with roles in beta-adrenergic signaling, including beta(3)-adrenergic receptor (16% increase in LCR; P < 0.05), NOR1 (24% decrease in LCR, 21% decrease in HCR; P < 0.05), phospho-ATGL (25% increase in HCR; P < 0.05), perilipin (25% increase in HCR; P < 0.05), CGI-58 (15% increase in LCR; P < 0.05), and GLUT4 (16% increase in HCR; P < 0.0001). A training effect was also observed for phospho-p38 MAPK (12% decrease in LCR, 20% decrease in HCR; P < 0.05) and phospho-JNK (29% increase in LCR, 20% increase in HCR; P < 0.05). We conclude that in the LCR-HCR model system, mitochondrial protein expression in WAT is not affected by intrinsic running capacity or exercise training. However, training does induce alterations in the activity and expression of several proteins that are essential to the intracellular regulation of WAT metabolism. C1 [Stephenson, Erin J.; Lessard, Sarah J.; Rivas, Donato A.; Hawley, John A.] RMIT Univ, Sch Med Sci, Bundoora, Vic, Australia. [Lessard, Sarah J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Rivas, Donato A.] Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Watt, Matthew J.] Monash Univ, Dept Physiol, Clayton, Vic 3168, Australia. [Yaspelkis, Ben B., III] Calif State Univ Northridge, Dept Kinesiol, Northridge, CA 91330 USA. [Koch, Lauren G.; Britton, Steven L.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Hawley, John A.] Liverpool John Moores Univ, Res Inst Sport & Exercise, Liverpool L3 5UX, Merseyside, England. RP Hawley, JA (reprint author), RMIT Univ, Sch Med Sci, POB 71, Bundoora, Vic 3083, Australia. EM john.hawley@rmit.edu.au RI Watt, Matthew/B-2089-2014; OI Rivas, Donato/0000-0002-4500-6233 FU National Heart Foundation [G 09M 4348]; National Center for Research Resources [R24 RR017718]; Office of Research Infrastructure Programs/OD from the National Institutes of Health [ROD012098A] FX This study was funded in part by a National Heart Foundation Grant-in-Aid (G 09M 4348) to J. A. Hawley. The LCR-HCR rat model system was funded specifically by National Center for Research Resources Grant R24 RR017718 and is currently supported by the Office of Research Infrastructure Programs/OD Grant ROD012098A (to L. G. Koch and S. L. Britton) from the National Institutes of Health. NR 77 TC 13 Z9 16 U1 2 U2 16 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 AUG PY 2013 VL 305 IS 3 BP E429 EP E438 DI 10.1152/ajpendo.00544.2012 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 195KS UT WOS:000322701700012 PM 23757406 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2013 VL 305 IS 3 BP 1203 EP 1204 DI 10.1152/ajplung.00119.2013 PG 2 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 195JY UT WOS:000322699500001 ER PT J AU Hamshere, ML Langley, K Martin, J Agha, SS Stergiakouli, E Anney, RJL Buitelaar, J Faraone, SV Lesch, KP Neale, BM Franke, B Sonuga-Barke, EJS Asherson, P Merwood, A Kuntsi, J Medland, SE Ripke, S Steinhausen, HC Freitag, C Reif, A Renner, TJ Romanos, M Romanos, J Warnke, A Meyer, J Palmason, H Vasquez, AA Lambregts-Rommelse, N Roeyers, H Biederman, J Doyle, AE Hakonarson, H Rothenberger, A Banaschewski, T Oades, RD McGough, JJ Kent, L Williams, N Owen, MJ Holmans, P O'Donovan, MC Thapar, A AF Hamshere, Marian L. Langley, Kate Martin, Joanna Agha, Sharifah Shameem Stergiakouli, Evangelia Anney, Richard J. L. Buitelaar, Jan Faraone, Stephen V. Lesch, Klaus-Peter Neale, Benjamin M. Franke, Barbara Sonuga-Barke, Edmund J. S. Asherson, Philip Merwood, Andrew Kuntsi, Jonna Medland, Sarah E. Ripke, Stephan Steinhausen, Hans-Christoph Freitag, Christine Reif, Andreas Renner, Tobias J. Romanos, Marcel Romanos, Jasmin Warnke, Andreas Meyer, Jobst Palmason, Haukur Vasquez, Alejandro Arias Lambregts-Rommelse, Nanda Roeyers, Herbert Biederman, Joseph Doyle, Alysa E. Hakonarson, Hakon Rothenberger, Aribert Banaschewski, Tobias Oades, Robert D. McGough, James J. Kent, Lindsey Williams, Nigel Owen, Michael J. Holmans, Peter O'Donovan, Michael C. Thapar, Anita TI High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY-DISORDER; GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; CONDUCT DISORDER; ANTISOCIAL-BEHAVIOR; OPPOSITIONAL DEFIANT; GENETIC-BASIS; AUTISM; SYMPTOMS AB Objective: Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. Method: Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. Results: Polygenic risk for ADD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by,the aggression items. Conclusions: Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity. C1 [Thapar, Anita] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. Trinity Ctr Hlth Sci, Dept Psychiat, Dublin, Ireland. Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6525 ED Nijmegen, Netherlands. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. Univ Wurzburg, ADHD Clin Res Network, Div Mol Psychiat, Dept Psychiat Psychosomat & Psychotherapy, D-97070 Wurzburg, Germany. Univ Wurzburg, Dept Child & Adolescent Psychiat, D-97070 Wurzburg, Germany. Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, London, England. Univ Southampton, Sch Psychol, Inst Disorder Impulse & Attent, Southampton, Hants, England. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Univ Basel, Inst Psychol, Basel, Switzerland. Aarhus Univ Hosp, Aalborg Psychiat Hosp, DK-8000 Aarhus, Denmark. Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland. Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, D-60054 Frankfurt, Germany. Univ Trier, Dept Neurobehav Genet, Inst Psychobiol, Trier, Germany. Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium. Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Ctr Appl Genom, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Gottingen, D-37073 Gottingen, Germany. Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany. Univ Duisburg Essen, Clin Child & Adolescent Psychiat, Essen, Germany. Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. Univ St Andrews, Sch Med, St Andrews, Fife, Scotland. RP Thapar, A (reprint author), Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. EM odonoyanmc@cf.ac.uk; thapar@cf.ac.uk RI Franke, Barbara/D-4836-2009; Arias Vasquez, Alejandro/E-4762-2012; Lesch, Klaus-Peter/J-4906-2013; Sonuga-Barke, Edmund/D-9137-2011; Kuntsi, Jonna/G-9750-2011; Romanos, Marcel/D-7695-2017; Renner, Tobias/I-2120-2013; Medland, Sarah/C-7630-2013; Holmans, Peter/F-4518-2015; Merwood, Andrew/F-8093-2012 OI O'Donovan, Michael/0000-0001-7073-2379; Kent, Lindsey/0000-0002-5315-3399; Martin, Joanna/0000-0002-8911-3479; Anney, Richard/0000-0002-6083-407X; Thapar, Anita/0000-0002-3689-737X; Faraone, Stephen/0000-0002-9217-3982; Stergiakouli, Evangelia/0000-0003-3586-0927; Franke, Barbara/0000-0003-4375-6572; Arias Vasquez, Alejandro/0000-0002-4786-0169; Lesch, Klaus-Peter/0000-0001-8348-153X; Langley, Kate/0000-0002-2033-2657; Medland, Sarah/0000-0003-1382-380X; Holmans, Peter/0000-0003-0870-9412; Merwood, Andrew/0000-0001-6719-9278 FU Alcobra; Shire; NIH; Eli Lilly; Janssen; McNeil; Novartis; Pfizer; Janssen-Cilag; Qbtech; King's College London from Shire; Vifor Pharma; Medice; Swedish Orphan International; Elminda; Fundacion Areces (Spain); Fundacion Dr. Manuel Camelo A.C.; Medice Pharmaceuticals; Spanish Child Psychiatry Association; Shionogi Pharma; Cipher Pharmaceuticals; German Research Society; Schwaabe; Lilly; Janssen McNeil; UCB; NeuroSigma; Shionogi; Supernus; Shire Pharmaceuticals; Wellcome Trust; Medical Research Council (U.K.); Action Research FX Dr. Buitelaar has served as a consultant, adviser, or speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myers Squibb, Schering Plough, UCB, Shire, Novartis, and Servier. Dr. Faraone has received consulting fees and support from Alcobra and Shire and support from NIH; he has received consulting or advisory board fees or participated in continuing medical education programs sponsored by Eli Lilly, Janssen, McNeil, Novartis, Pfizer, and Shire and has received royalties from Guilford Press and Oxford University Press. Dr. Sonuga-Barke has been involved in the development, implementation, and trialing of the New Forest Parenting Programme for preschool children with ADHD and has received royalties from sales of a New Forest Parent Training self-help manual; he has served as a speaker, adviser, or consultant for AstraZeneca, Flynn Pharma, Shire, and UCB Pharma, has received conference support from Shire, and has received research support from Janssen-Cilag, Shire, and Qbtech. Dr. Asherson has received payments on behalf of King's College London from Shire, Eli Lilly, Janssen-Cilag, and Vifor Pharma for advisory work, speaking, and educational and/or research grants. Dr. Steinhausen has served as an adviser and speaker for Janssen-Cilag, Eli Lilly, Novartis, Medice, Shire, and UCB; he has received unrestricted grants for postgraduate training courses or conferences and research from Janssen-Cilag, Eli Lilly, Novartis, Medice, and Swedish Orphan International. Dr. Freitag has been on speakers bureaus for Eli Lilly, Novartis, and Shire. Dr. Biederman has received research support from Elminda, Janssen, McNeil, and Shire; speaking fees from Fundacion Areces (Spain), Fundacion Dr. Manuel Camelo A.C., Medice Pharmaceuticals, and the Spanish Child Psychiatry Association; consulting fees from Shionogi Pharma and Cipher Pharmaceuticals (honoraria were paid to the Department of Psychiatry at Massachusetts General Hospital [MGH]); honoraria from the MGH Psychiatry Academy for a tuition-funded CME course; an honorarium from Cambridge University Press for a chapter publication; and departmental royalties for a rating scale used for ADHD diagnosis (paid by Eli Lilly, Shire, and AstraZeneca to the Department of Psychiatry at MGH). Dr. Rothenberger has served as an adviser, consultant, or speaker for Lilly, Shire, Medice, Novartis, and UCB/Shire; he has received research support from Shire, German Research Society, and Schwaabe and travel support and an educational grant from Shire. Dr. Banaschewski has served as an adviser or consultant for Bristol Myers-Squibb, Develco Pharma, Lilly, Medice, Novartis, Shire, and Viforpharma; he has received conference attendance support-and conference support or speaking fees from Lilly, Janssen McNeil, Medice, Novartis, and Shire, and he has been involved in clinical trials conducted by Lilly and Shire. Dr. Oades has received research funding and conference attendance support from UCB, Janssen-Cilag, and Shire. Dr. McGough has served as a consultant for Next Wave, Noven, Targacept, Theravance, and Shionogi Pharmaceuticals and has received research support from NeuroSigma, Shionogi, Supernus, and Shire Pharmaceuticals.; Supported by Wellcome Trust, the Medical Research Council (U.K.), and Action Research. Acknowledgments for the published ADHD meta-analysis data are detailed in reference 1. NR 47 TC 38 Z9 39 U1 3 U2 28 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2013 VL 170 IS 8 BP 909 EP 916 DI 10.1176/appi.ajp.2013.12081129 PG 8 WC Psychiatry SC Psychiatry GA 194DO UT WOS:000322611400015 PM 23599091 ER PT J AU Franko, DL Keshaviah, A Eddy, KT Krishna, M Davis, MC Keel, PK Herzog, DB AF Franko, Debra L. Keshaviah, Aparna Eddy, Kamryn T. Krishna, Meera Davis, Martha C. Keel, Pamela K. Herzog, David B. TI A Longitudinal Investigation of Mortality in Anorexia Nervosa and Bulimia Nervosa SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID EATING-DISORDERS; FOLLOW-UP; OUTCOME PREDICTORS; PROGNOSTIC-FACTORS; DSM-V; DEATH; RECOVERY; INTERVAL; RELAPSE; RATES AB Objective: Although anorexia nervosa has a high mortality rate, our understanding of the timing and predictors of mortality in eating disorders is limited. The authors investigated mortality in a long-term study of patients with eating disorders. Method: Beginning in 1987, 246 treatment-seeking female patients with anorexia nervosa or bulimia nervosa were interviewed every 6 months for a median of 9.5 years to obtain weekly ratings of eating disorder symptoms, comorbidity, treatment participation, and psychosocial functioning. From January 2007 to December 2010 (median follow-up of 20 years), vital status was ascertained with a National Death Index search. Results: Sixteen deaths (6.5%) were recorded (lifetime anorexia nervosa, N=14; bulimia nervosa with no history of anorexia nervosa, N=2). The standardized mortality ratio was 4.37 (95% CI=2.4-7.3) for lifetime anorexia nervosa and 2.33 (95% CI=0.3-8.4) for bulimia nervosa with no history of anorexia nervosa. Risk of premature death among patients with lifetime anorexia nervosa peaked within the first 10 years of follow-up, resulting in a standardized mortality ratio of 7.7 (95% CI=3.7-14.2). The standardized mortality ratio varied by duration of illness and was 3.2(95% CI=0.9-8.3) for patients with lifetime anorexia nervosa for 0 to 15 years (4/119 died), and 6.6 (95% CI=3.2-12.1) for those with lifetime anorexia nervosa for >15 to 30 years (10/67 died). Multivariate predictors of mortality included alcohol abuse, low body mass index, and poor social adjustment. Conclusions: These findings highlight the need for early identification and intervention and suggest that a long duration of illness, substance abuse, low weight, and poor psychosocial functioning raise the risk for mortality in anorexia nervosa. C1 [Franko, Debra L.] Massachusetts Gen Hosp, Harris Ctr Educ & Advocacy Eating Disorders, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Franko, DL (reprint author), Massachusetts Gen Hosp, Harris Ctr Educ & Advocacy Eating Disorders, Boston, MA 02114 USA. EM d.franko@neu.edu FU NIMH [R01 MH-38333, R03 MH-094832] FX Supported by NIMH grants R01 MH-38333 (to Dr. Herzog) and R03 MH-094832 (to Drs. Eddy and Herzog). NR 33 TC 48 Z9 49 U1 6 U2 62 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 AUG PY 2013 VL 170 IS 8 BP 917 EP 925 DI 10.1176/appi.ajp.2013.12070868 PG 9 WC Psychiatry SC Psychiatry GA 194DO UT WOS:000322611400016 PM 23771148 ER PT J AU Hess, DR Thompson, BT Slutsky, AS AF Hess, Dean R. Thompson, B. Taylor Slutsky, Arthur S. TI Update on Acute Respiratory Distress Syndrome and Mechanical Ventilation 2012 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACUTE LUNG INJURY; CRITICALLY-ILL PATIENTS; RANDOMIZED CONTROLLED-TRIAL; END-EXPIRATORY PRESSURE; INVASIVE PULMONARY ASPERGILLOSIS; NONINVASIVE VENTILATION; PROTECTIVE VENTILATION; RELEASE VENTILATION; BERLIN DEFINITION; FLUID-MANAGEMENT C1 [Hess, Dean R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Dept Med, Boston, MA 02114 USA. [Hess, Dean R.; Thompson, B. Taylor] Harvard Univ, Sch Med, Boston, MA USA. [Slutsky, Arthur S.] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Slutsky, Arthur S.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Slutsky, Arthur S.] Univ Toronto, Dept Med, Toronto, ON, Canada. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 71 TC 2 Z9 2 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2013 VL 188 IS 3 BP 285 EP 292 DI 10.1164/rccm.201304-0786UP PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 194GA UT WOS:000322617800009 PM 23905523 ER PT J AU Matthay, MA Anversa, P Bhattacharya, J Burnett, BK Chapman, HA Hare, JM Hei, DJ Hoffman, AM Kourembanas, S McKenna, DH Ortiz, LA Ott, HC Tente, W Thebaud, B Trapnell, BC Weiss, DJ Yuan, JXJ Blaisdell, CJ AF Matthay, Michael A. Anversa, Piero Bhattacharya, Jahar Burnett, Bruce K. Chapman, Harold A. Hare, Joshua M. Hei, Derek J. Hoffman, Andrew M. Kourembanas, Stella McKenna, David H. Ortiz, Luis A. Ott, Harald C. Tente, William Thebaud, Bernard Trapnell, Bruce C. Weiss, Daniel J. Yuan, Jason X. -J. Blaisdell, Carol J. TI Cell Therapy for Lung Diseases Report from an NIH-NHLBI Workshop, November 13-14, 2012 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE mesenchymal stromal (stem) cells; epithelial and endothelial progenitor cells; lung stem cells ID MESENCHYMAL STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; BRONCHOPULMONARY DYSPLASIA; PULMONARY-HYPERTENSION; MITOCHONDRIAL TRANSFER; RANDOMIZED-TRIAL; STROMAL CELLS; BASAL-CELLS; REGENERATION; INJURY AB The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13-14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy. C1 [Matthay, Michael A.; Chapman, Harold A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Anversa, Piero] Harvard Univ, Sch Med, Dept Anesthesia & Med, Boston, MA USA. [Bhattacharya, Jahar] Columbia Univ, Dept Med, New York, NY USA. [Burnett, Bruce K.] Duke Univ, Sch Med, Duke Translat Med Inst, Durham, NC USA. [Hare, Joshua M.] Univ Miami, Dept Med, Miami, FL USA. [Hei, Derek J.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. [Hoffman, Andrew M.] Tufts Univ, Dept Clin Sci, Cummings Sch Vet Med, North Grafton, MA USA. [Kourembanas, Stella] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [McKenna, David H.] Univ Minnesota, Dept Mol & Cellular Therapeut, St Paul, MN 55108 USA. [Ortiz, Luis A.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA. [Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Tente, William] Humacyte Inc, Res Triangle Pk, NC USA. [Thebaud, Bernard] Univ Ottawa, Dept Pediat, Ottawa, ON K1N 6N5, Canada. [Trapnell, Bruce C.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Weiss, Daniel J.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Yuan, Jason X. -J.] Univ Illinois, Dept Med, Coll Med Chicago, Chicago, IL USA. [Blaisdell, Carol J.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. RP Blaisdell, CJ (reprint author), NHLBI, NIH, 6701 Rockledge Dr,10-042, Bethesda, MD 20892 USA. EM blaisdellcj@nhlbi.nih.gov RI ortiz, luis/H-9851-2013; OI ortiz, luis/0000-0003-4510-7066 FU National Heart, Lung, and Blood Institute, National Institutes of Health FX Supported by the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 36 TC 8 Z9 8 U1 0 U2 16 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2013 VL 188 IS 3 BP 370 EP 375 DI 10.1164/rccm.201303-0522WS PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 194GA UT WOS:000322617800019 PM 23713908 ER PT J AU Amri, R den Boon, HC Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi den Boon, Hannah C. Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI The impact of adhesions on operations and postoperative recovery in colon cancer surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Intra-abdominal adhesions; Colon cancer; Complications; Stay duration; Surgery duration ID PERITONEAL ADHESIONS; GENERAL-SURGERY; COMPLICATIONS; CONVERSION; LAPAROTOMY; MORBIDITY; TIME AB BACKGROUND: Many surgeons assume that adhesions encountered during surgery negatively influence surgical outcomes. This article attempts to assess the role adhesions have on outcomes of colon cancer surgery. METHODS: Records of 1,071 consecutive patients operated for colonic adenocarcinoma (2004-2011) were reviewed. Patients were assigned to 3 groups: no adhesions, any adhesions, or dense adhesions. Multivariate regression assessed the association between adhesions and the duration of surgery and stay as well as laparoscopic conversion and complication rates. RESULTS: Adhesions were encountered in 329 (30.7%) patients; 138 (12.8%) had dense adhesions. After correction for age and comorbidities, having adhesions was associated with longer surgeries (P < .001), longer hospital stays (P = .029), a borderline significantly higher conversion rate (P = .058), and a delayed return of bowel function (P = .037). Dense adhesions had stronger associations with surgical duration (P < .001), stay duration (P < .001), and conversion (P < .001). CONCLUSIONS: Abdominal adhesions independently put patients at risk for a longer and more complicated perioperative stay after colon cancer surgery. (C) 2013 Elsevier Inc. All rights reserved. C1 [Amri, Ramzi; den Boon, Hannah C.; Bordeianou, Liliana G.; Sylla, Patricia; Berger, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Surg & Gastrointestinal Surg, Boston, MA 02114 USA. RP Berger, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Surg & Gastrointestinal Surg, Boston, MA 02114 USA. EM dberger@partners.org OI Amri, Ramzi/0000-0001-7416-6650 FU Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award) [8UL1TR000170-05]; Dutch Cancer Society; Dutch Digestive Society; Amsterdam University Funds; Fulbright Foundation FX Supported by the Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health care centers) and the Dutch Cancer Society, the Dutch Digestive Society, the Amsterdam University Funds, and the Fulbright Foundation. NR 17 TC 8 Z9 8 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD AUG PY 2013 VL 206 IS 2 BP 166 EP 171 DI 10.1016/j.amjsurg.2013.01.018 PG 6 WC Surgery SC Surgery GA 195MV UT WOS:000322707900004 PM 23561641 ER PT J AU Yeh, H Hunsicker, L AF Yeh, H. Hunsicker, L. TI Deceased Donor Liver Allocation: Cutting the Gordian Knot SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID TRANSPLANTATION C1 [Yeh, H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hunsicker, L.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. RP Yeh, H (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM hyeh@partners.org NR 6 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 2013 VL 13 IS 8 BP 1949 EP 1950 DI 10.1111/ajt.12302 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 190HM UT WOS:000322330000005 PM 23890283 ER PT J AU Jin, JO Kawai, T Cha, S Yu, Q AF Jin, Jun-O Kawai, Toshihisa Cha, Seunghee Yu, Qing TI Interleukin-7 Enhances the Th1 Response to Promote the Development of Sjogren's Syndrome-like Autoimmune Exocrinopathy in Mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; SYNDROME-LIKE DISEASE; T-CELL FUNCTION; SALIVARY-GLAND; INTERFERON-GAMMA; MOUSE MODEL; CHRONIC COLITIS; KNOCKOUT MICE; EXPRESSION; IL-7 AB Objective. Although elevated interleukin-7 (IL-7) levels have been reported in patients with primary Sjogren's syndrome (SS), the role of IL-7 in this disease remains unclear. We undertook this study to characterize the previously unexplored role of IL-7 in the development and onset of primary SS using the C57BL/6. NOD-Aec1Aec2 (B6.NOD-Aec) mouse model, which recapitulates human primary SS. Methods. For gain-of-function studies, recombinant IL-7 or control phosphate buffered saline was injected intraperitoneally (IP) into 12-week-old B6.NOD-Aec mice for 8 weeks. For loss-of-function studies, anti-IL-7 receptor alpha-chain (anti-IL-7R alpha) antibody or its isotype control IgG was administered IP into 16-week-old B6.NOD-Aec mice. Salivary flow measurement, histologic and flow cytometric analysis of salivary glands, and serum antinuclear antibody assay were performed to assess various disease parameters. Results. Administration of exogenous IL-7 accelerated the development of primary SS, whereas blockade of IL-7R alpha signaling almost completely abolished the development of primary SS, based on salivary gland inflammation and apoptosis, autoantibody production, and secretory dysfunction. IL-7 positively regulated interferon-gamma (IFN gamma)-producing Th1 and CD8+ T cells in the salivary glands without affecting IL-17. Moreover, IL-7 enhanced the expression of CXCR3 ligands in a T cell- and IFN gamma-dependent manner. Accordingly, IFN gamma induced a human salivary gland epithelial cell line to produce CXCR3 ligands. IL-7 also increased the level of tumor necrosis factor alpha, another Th1-associated cytokine that can facilitate tissue destruction and inflammation. Conclusion. IL-7 plays a pivotal pathogenic role in SS, which is underpinned by an enhanced Th1 response and IFN gamma/CXCR3 ligand-mediated lymphocyte infiltration of target organs. These results suggest that targeting the IL-7 pathway may be a potential future strategy for preventing and treating SS. C1 [Jin, Jun-O; Kawai, Toshihisa; Yu, Qing] Forsyth Inst, Cambridge, MA 02142 USA. [Cha, Seunghee] Univ Florida, Gainesville, FL USA. RP Yu, Q (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 1st St, Cambridge, MA 02142 USA. EM qyu@forsyth.org FU NIH [P30-DE-020751] FX Supported by the NIH (grant P30-DE-020751). NR 49 TC 18 Z9 20 U1 1 U2 3 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 AUG PY 2013 VL 65 IS 8 BP 2132 EP 2142 DI 10.1002/art.38007 PG 11 WC Rheumatology SC Rheumatology GA 190HD UT WOS:000322329100023 PM 23666710 ER PT J AU Carruthers, MN Miloslavsky, EM Stone, JH AF Carruthers, Mollie N. Miloslavsky, Eli M. Stone, John H. TI IgG4-related pharyngitis-an addition to the nomenclature of IgG4-related disease: comment on the article by Stone et al Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID MANIFESTATIONS C1 [Carruthers, Mollie N.; Miloslavsky, Eli M.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. RP Carruthers, MN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 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 AUG PY 2013 VL 65 IS 8 BP 2217 EP 2218 DI 10.1002/art.37998 PG 2 WC Rheumatology SC Rheumatology GA 190HD UT WOS:000322329100037 PM 23677887 ER PT J AU Fatemi, G Fang, MA AF Fatemi, Gita Fang, Meika A. TI IgG4-related pharyngitis-an addition to the nomenclature of IgG4-related disease: comment on the article by Stone et al SO ARTHRITIS AND RHEUMATISM LA English DT Letter C1 [Fatemi, Gita] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Fatemi, G (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 3 TC 3 Z9 3 U1 0 U2 1 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 AUG PY 2013 VL 65 IS 8 BP 2217 EP 2218 DI 10.1002/art.37999 PG 2 WC Rheumatology SC Rheumatology GA 190HD UT WOS:000322329100036 PM 23666890 ER PT J AU Delaney, JA Lehmann, N Jockel, KH Elmariah, S Psaty, BM Mahabadi, AA Budoff, M Kronmal, RA Nasir, K O'Brien, KD Mohlenkamp, S Moebus, S Dragano, N Winterstein, AG Erbel, R Kalsch, H AF Delaney, Joseph A. Lehmann, Nils Joeckel, Karl-Heinz Elmariah, Sammy Psaty, Bruce M. Mahabadi, Amir A. Budoff, Matt Kronmal, Richard A. Nasir, Khurram O'Brien, Kevin D. Moehlenkamp, Stefan Moebus, Susanne Dragano, Nico Winterstein, Almut G. Erbel, Raimund Kalsch, Hagen TI Associations between aspirin and other non-steroidal anti-inflammatory drugs and aortic valve or coronary artery calcification: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study SO ATHEROSCLEROSIS LA English DT Article DE Non-steroidal anti-inflammatory drugs; Aspirin; Aortic valve calcification; Coronary artery calcification; Multi-Ethnic Study of Atherosclerosis; Heinz Nixdorf Recall Study ID CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; PRIMARY PREVENTION; RISK; MORTALITY; UPDATE; HEALTH; MESA; REPRODUCIBILITY; QUANTIFICATION AB Background: The association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events. Objective: To compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcification (CAC). Methods: The relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication. Results: Mean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95% Confidence Interval (CI): 1.19-2.15) did not replicate in the HNR cohort (RR: 1.06; 95% CI: 0.87-1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95% CI: 0.91-1.29) or in the HNR cohort (RR 1.24; 95% CI: 0.87-1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in either cohort. Conclusion: Baseline NSAID use, as assessed by medication inventory, appears to have no protective effect regarding the onset of calcification in either coronary arteries or aortic valves. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Delaney, Joseph A.; Winterstein, Almut G.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Delaney, Joseph A.; Kronmal, Richard A.] Univ Washington, Sch Publ Hlth, Seattle, WA 98115 USA. [Lehmann, Nils; Joeckel, Karl-Heinz; Moebus, Susanne] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Duisburg, Germany. [Elmariah, Sammy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Psaty, Bruce M.] Univ Washington, Cardiovascular Hlth Res Unit, Dept Med, Seattle, WA 98115 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98115 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Mahabadi, Amir A.; Moehlenkamp, Stefan; Erbel, Raimund; Kalsch, Hagen] Univ Duisburg Essen, Dept Cardiol, West German Heart Ctr Essen, Duisburg, Germany. [Budoff, Matt] Harbour UCLA, Los Angeles Biomed Res Inst, Torrance, CA USA. [Nasir, Khurram] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [O'Brien, Kevin D.] Univ Washington, Dept Med, Seattle, WA 98115 USA. [Dragano, Nico] Univ Dusseldorf, Inst Med Sociol, Dusseldorf, Germany. RP Delaney, JA (reprint author), Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Bldg 29,Suite 210,Box 354922,6200 NE 74th St, Seattle, WA 98115 USA. EM jacd@uw.edu RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 FU National Heart, Lung, and Blood Institute [R01-HL071739, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169]; New Pharmacy Faculty Research Award from the American Association of Colleges of Pharmacy (Delaney); Heinz Nixdorf Foundation, Essen, Germany; Deutsche Forschungsgemeinschaft (DFG); American Association of Colleges of Pharmacy through their New Pharmacy Faculty Research Awards Program FX This research was supported by R01-HL071739 and contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, the staff, and the participants of the MESA and HNR studies for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This study was also supported by a New Pharmacy Faculty Research Award from the American Association of Colleges of Pharmacy (Delaney).; The Heinz Nixdorf Recall Study is funded by a contract with the private Heinz Nixdorf Foundation, Essen, Germany and undergoes continuous monitoring by governmental agencies (DLR) lead by the Bundesministerium fur Bildung und Forschung (BMBF). This research is also supported by the Deutsche Forschungsgemeinschaft (DFG) and by the American Association of Colleges of Pharmacy through their New Pharmacy Faculty Research Awards Program. NR 30 TC 3 Z9 3 U1 0 U2 7 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 AUG PY 2013 VL 229 IS 2 BP 310 EP 316 DI 10.1016/j.atherosclerosis.2013.05.002 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 190CZ UT WOS:000322316900007 PM 23880181 ER PT J AU Tarnoki, AD Tarnoki, DL Bogl, LH Medda, E Fagnani, C Nistico, L Stazi, MA Brescianini, S Lucatelli, P Boatta, E Zini, C Fanelli, F Baracchini, C Meneghetti, G Osztovits, J Jermendy, G Kiss, RG Preda, I Karlinger, K Lannert, A Molnar, AA Littvay, L Garami, Z Berczi, V Pucci, G Baffy, G Schillaci, G Pietilainen, KH AF Tarnoki, Adam Domonkos Tarnoki, David Laszlo Bogl, Leonie H. Medda, Emanuela Fagnani, Corrado Nistico, Lorenza Stazi, Maria Antonietta Brescianini, Sonia Lucatelli, Pierleone Boatta, Emanuele Zini, Chiara Fanelli, Fabrizio Baracchini, Claudio Meneghetti, Giorgio Osztovits, Janos Jermendy, Gyorgy Kiss, Robert Gabor Preda, Istvan Karlinger, Kinga Lannert, Agnes Molnar, Andrea Agnes Littvay, Levente Garami, Zsolt Berczi, Viktor Pucci, Giacomo Baffy, Gyorgy Schillaci, Giuseppe Pietilainen, Kirsi H. TI Association of body mass index with arterial stiffness and blood pressure components: A twin study SO ATHEROSCLEROSIS LA English DT Article DE Central blood pressure; Augmentation index; Pulse wave velocity; Hypertension; Obesity; Twin study ID ENVIRONMENTAL-INFLUENCES; MONOZYGOTIC TWINS; AORTIC STIFFNESS; AFRICAN-AMERICAN; WAVE REFLECTION; RISK-FACTORS; HERITABILITY; OBESITY; HYPERTENSION; WOMEN AB Rationale: Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown. Methods: We studied 228 monozygotic and 150 dizygotic twin pairs aged 18-82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Delta) in BMI >= 3 kg/m(2)). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph. Results: Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p < 0.001). Age-, sex-and country-adjusted heritability estimates were high for hemodynamic measures (45%-58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = -0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors (65%-77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, Delta BMI was significantly correlated with Delta brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Delta mean arterial pressure, and Delta aortic SBP (r = 0.15-0.17, p < 0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p < 0.05). Conclusion: Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Karlinger, Kinga; Berczi, Viktor] Semmelweis Univ, Dept Radiol & Oncotherapy, H-1082 Budapest, Hungary. [Bogl, Leonie H.] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Medda, Emanuela; Fagnani, Corrado; Nistico, Lorenza; Stazi, Maria Antonietta; Brescianini, Sonia] Ist Super Santa, Natl Ctr Epidemiol Surveillance & Hlth Promot, Genet Epidemiol Unit, Rome, Italy. [Lucatelli, Pierleone; Boatta, Emanuele; Zini, Chiara; Fanelli, Fabrizio] Univ Roma La Sapienza, Dept Radiol Sci, Vasc & Intervent Radiol Unit, I-00185 Rome, Italy. [Baracchini, Claudio; Meneghetti, Giorgio] Univ Padua, Sch Med, Dept Neurosci, Padua, Italy. [Osztovits, Janos; Jermendy, Gyorgy] Bajcsy Zsilinszky Hosp, Dept Internal Med 3, Budapest, Hungary. [Kiss, Robert Gabor; Preda, Istvan; Molnar, Andrea Agnes] Hungarian Acad Sci, Res Grp Inflammat Biol & Immunogenom, Budapest, Hungary. [Kiss, Robert Gabor; Preda, Istvan; Molnar, Andrea Agnes] Semmelweis Univ, H-1085 Budapest, Hungary. [Kiss, Robert Gabor; Preda, Istvan; Molnar, Andrea Agnes] Mil Hosp, Dept Cardiol, Budapest, Hungary. [Lannert, Agnes] Semmelweis Univ, Sch Pharm, H-1085 Budapest, Hungary. [Littvay, Levente] Cent European Univ, Budapest, Hungary. [Garami, Zsolt] DeBakey Heart & Vasc Ctr, Methodist Hosp, Houston, TX USA. [Baffy, Gyorgy] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Baffy, Gyorgy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Pietilainen, Kirsi H.] Helsinki Univ Cent Hosp, Obes Res Unit, Div Endocrinol, Dept Med, Helsinki, Finland. [Pietilainen, Kirsi H.] Univ Helsinki, Helsinki, Finland. [Pietilainen, Kirsi H.] Univ Helsinki, FIMM, Inst Mol Med Finland, Helsinki, Finland. RP Tarnoki, AD (reprint author), Semmelweis Univ, Dept Radiol & Oncotherapy, 78-A Ulloi St, H-1082 Budapest, Hungary. EM tarnoki2@gmail.com RI Fagnani, Corrado/J-9069-2016; stazi, maria /K-4597-2016; Lucatelli, Pierleone/R-3188-2016 OI Fagnani, Corrado/0000-0001-5771-7772; Lucatelli, Pierleone/0000-0002-7448-1404 FU Twins Days Festival committee FX We would like to acknowledge the support of Twins Days Festival committee and Stephen F. Luczek, MD for the American part of the study. We thank Sabrina Alviti and Antonio Arnofi for technical assistance and management of Italian Twin Registry data. NR 49 TC 12 Z9 14 U1 0 U2 26 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 AUG PY 2013 VL 229 IS 2 BP 388 EP 395 DI 10.1016/j.atherosclerosis.2013.05.001 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 190CZ UT WOS:000322316900019 PM 23880193 ER PT J AU Thoreen, CC AF Thoreen, Carson C. TI Many roads from mTOR to eIF4F SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE eukaryotic initiation factor 4E-binding protein 1 (4E-BP1); eukaryotic initiation factor 4F (eIF4F); mammalian target of rapamycin (mTOR); PP242; Torin1; translation ID CAP-BINDING PROTEIN; TRANSLATION INITIATION; CANCER; GROWTH; PHOSPHORYLATION; ASSOCIATION; ACTIVATION; MICE AB The process of cell growth depends on a complex co-ordinated programme of macromolecular synthesis that can be tuned to environmental constraints. In eukaryotes, the mTOR [mammalian (or mechanistic) target of rapamycin] signalling pathway is a master regulator of this process, in part by regulating mRNA translation through control of the eIF4F (eukaryotic initiation factor 4F) initiation complex. The present review discusses the role of this relationship in mTOR-regulated gene expression, and its contribution to phenotypes associated with deregulated mTOR signalling, such as cancer. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Thoreen, CC (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 250 Longwood Ave, Boston, MA 02115 USA. EM carson_thoreen@dfci.harvard.edu FU American Cancer Society FX I am supported by a postdoctoral fellowship from the American Cancer Society. NR 29 TC 13 Z9 13 U1 0 U2 8 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 2013 VL 41 BP 913 EP 916 DI 10.1042/BST20130082 PN 4 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 193LU UT WOS:000322562100019 PM 23863155 ER PT J AU Omer, AK Ziakas, PD Anagnostou, T Coughlin, E Kourkoumpetis, T McAfee, SL Dey, BR Attar, E Chen, YB Spitzer, TR Mylonakis, E Ballen, KK AF Omer, Aazim K. Ziakas, Panayiotis D. Anagnostou, Theodora Coughlin, Erin Kourkoumpetis, Themistoklis McAfee, Steven L. Dey, Bimalangshu R. Attar, Eyal Chen, Yi-Bin Spitzer, Thomas R. Mylonakis, Eleftherios Ballen, Karen K. TI Risk Factors for Invasive Fungal Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Invasive fungal disease; Allogeneic hematopoietic stem; cell transplantation; CD34(+) cell ID VERSUS-HOST-DISEASE; IDENTICAL SIBLING TRANSPLANTATION; COLONY-STIMULATING FACTOR; BONE-MARROW-TRANSPLANTATION; G-CSF; MOLD INFECTIONS; IMMUNE RECONSTITUTION; PROGENITOR CELLS; HEALTHY DONORS; HIGHER CD34(+) AB Invasive fungal disease (IFD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HCT). We performed a retrospective review of 271 adults with a hematologic malignancy undergoing allogeneic HCT to determine the incidence of and risk factors for IFD and to examine the impact of IFD on nonrelapse mortality and overall survival. We defined IFD using standard criteria and selected proven and probable cases for analysis. Diagnoses in the study group included acute leukemia (42%), non-Hodgkin lymphoma (24%), myelodysplastic syndrome (15%), chronic lymphocytic leukemia (5%), and other hematologic disorders (14%). Conditioning included reduced-intensity (64%) and myeloablative (36%) regimens. Donor sources were HLA-matched sibling (60%), matched unrelated (20%), haploidentical (12%), and cord blood (8%). A total of 51 episodes of IFD were observed in 42 subjects (15%). Aspergillus spp (47%) was the most frequent causative organism, followed by Candida spp (43%). The majority of IFD cases (67%) were reported after day +100 post-HCT. In multivariate analysis, haploidentical donor transplantation (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.49-9.77; P = .005) and grade II-IV acute graft-versus-host disease (HR, 2.55; 95% CI, 1.07-6.10; P = .03) were risk factors for the development of IFD. Conversely, higher infused CD34(+) cell dose was associated with a lower risk of IFD (HR, 0.80; 95% CI, 0.68-0.94; P = .006, per 1 x 10(6) cells/kg increase in CD34(+) cell infusion). IFD-related mortality was 33.3%. Nonrelapse mortality was significantly higher in patients who developed IFD compared with those without IFD (P < .001, log-rank test). Patients with IFD had lower overall survival (5.8 months versus 76.1 months; P < .001, log-rank test). Further studies exploring strategies to increase the infused cell dose and determine adequate prophylaxis, especially against aspergillus, beyond day +100 are needed. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Omer, Aazim K.] North Shore Med Ctr, Dept Med, Salem, MA USA. [Ziakas, Panayiotis D.; Mylonakis, Eleftherios] Brown Univ, Div Infect Dis, Warren Alpert Med Sch, Providence, RI 02912 USA. [Anagnostou, Theodora] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Coughlin, Erin; McAfee, Steven L.; Dey, Bimalangshu R.; Attar, Eyal; Chen, Yi-Bin; Spitzer, Thomas R.; Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. [Kourkoumpetis, Themistoklis] Boston Univ, Dept Internal Med, Boston Med Ctr, Boston, MA 02215 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 0 Emerson Pl,Suite 118, Boston, MA 02114 USA. EM kballen@partners.org FU Astellas Inc; T2 Biosystems FX Eleftherios E. Mylonakis received research support from Astellas Inc and T2 Biosystems. NR 61 TC 18 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2013 VL 19 IS 8 BP 1190 EP 1196 DI 10.1016/j.bbmt.2013.05.018 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 194BW UT WOS:000322607000011 PM 23747459 ER PT J AU Gadalla, SM Sales-Bonfim, C Carreras, J Alter, BP Antin, JH Ayas, M Bodhi, P Davis, J Davies, SM Deconinck, E Deeg, HJ Duerst, RE Fasth, A Ghavamzadeh, A Giri, N Goldman, FD Kolb, EA Krance, R Kurtzberg, J Leung, WH Srivastava, A Or, R Richman, CM Rosenberg, PS Codina, JSD Shenoy, S Socie, G Tolar, J Williams, KM Eapen, M Savage, SA AF Gadalla, Shahinaz M. Sales-Bonfim, Carmem Carreras, Jeanette Alter, Blanche P. Antin, Joseph H. Ayas, Mouhab Bodhi, Prasad Davis, Jeffrey Davies, Stella M. Deconinck, Eric Deeg, H. Joachim Duerst, Reggie E. Fasth, Anders Ghavamzadeh, Ardeshir Giri, Neelam Goldman, Frederick D. Kolb, E. Anders Krance, Robert Kurtzberg, Joanne Leung, Wing H. Srivastava, Alok Or, Reuven Richman, Carol M. Rosenberg, Philip S. de Toledo Codina, Jose Sanchez Shenoy, Shalini Socie, Gerard Tolar, Jakub Williams, Kirsten M. Eapen, Mary Savage, Sharon A. TI Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Dyskeratosis Congenita SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Dyskeratosis congenita; Allogeneic transplantation; Long-term survival; Pulmonary toxicity ID BONE-MARROW FAILURE; TELOMERE BIOLOGY; APLASTIC-ANEMIA; MUTATIONS; ENGRAFTMENT; DISORDERS; DISEASE AB We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita who underwent transplantation between 1981 and 2009. The median age at transplantation was 13 years (range, 2 to 35). Approximately 50% of transplantations were from related donors. Bone marrow was the predominant source of stem cells (24 of 34). The day-28 probability of neutrophil recovery was 73% and the day-100 platelet recovery was 72%. The day-100 probability of grade II to IV acute GVHD and the 3-year probability of chronic graft-versus-host disease were 24% and 37%, respectively. The 10-year probability of survival was 30%; 14 patients were alive at last follow-up. Ten deaths occurred within 4 months from transplaneation because of graft failure (n = 6) or other transplantation-related complications; 9 of these patients had undergone transplantation from mismatched related or from unrelated donors. Another 10 deaths occurred after 4 months; 6 of them occurred more than 5 years after transplantation, and 4 of these were attributed to pulmonary failure. Transplantation regimen intensity and transplantations from mismatched related or unrelated donors were associated with early mortality. Transplantation of grafts from HLA-matched siblings with cyclophosphamide-containing nonradiation regimens was associated with early low toxicity. Late mortality was attributed mainly to pulmonary complications and likely related to the underlying disease. (C) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Gadalla, Shahinaz M.; Alter, Blanche P.; Giri, Neelam; Rosenberg, Philip S.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sales-Bonfim, Carmem] Univ Fed Parana, Hosp Clin Curitiba, BR-80060000 Curitiba, Parana, Brazil. [Carreras, Jeanette; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ayas, Mouhab] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia. [Bodhi, Prasad] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Davis, Jeffrey] British Columbia Childrens Hosp, Dept Paediat, BMT Serv, Vancouver, BC V6H 3V4, Canada. [Davies, Stella M.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Deconinck, Eric] Hop Jean Minjoz, Serv Hematol D, F-25030 Besancon, France. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Duerst, Reggie E.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Fasth, Anders] Univ Gothenburg, Dept Pediat, Gothenburg, Sweden. [Ghavamzadeh, Ardeshir] Univ Tehran Med Sci, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran. [Goldman, Frederick D.] Univ Alabama Birmingham, Birmingham, AL USA. [Kolb, E. Anders] Alfred I Dupont Hosp Children, Wilmington, DE USA. [Krance, Robert] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Kurtzberg, Joanne] Duke Univ, Med Ctr, Durham, NC USA. [Leung, Wing H.] St Jude Childrens Res Hosp, Div Bone Marrow Transplantat, Memphis, TN 38105 USA. [Srivastava, Alok] Christian Med Coll & Hosp, Dept Haematol, Vellore, Tamil Nadu, India. [Or, Reuven] Hadassah Univ Hosp, Dept Bone Marrow Transplantat, IL-91120 Jerusalem, Israel. [Richman, Carol M.] Univ Calif Davis, Davis Canc Ctr, Div Hematol Oncol, Sacramento, CA 95817 USA. [de Toledo Codina, Jose Sanchez] Hosp Infantil Vall dHebron, Paediat Oncol Haematol & SCT Dept, Barcelona, Spain. [Shenoy, Shalini] Washington Univ, St Louis Childrens Hosp, St Louis, MO 63110 USA. [Socie, Gerard] Hosp St Louis, Paris, France. [Tolar, Jakub] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Williams, Kirsten M.] George Washington Univ, Med Ctr, Childrens Natl Med Ctr, Ctr Canc & Blood Disorders,Div Blood & Marro Tran, Washington, DC 20037 USA. [Williams, Kirsten M.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Eapen, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 West Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM meapen@mcw.edu RI Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Fasth, Anders/0000-0002-0033-740X; Tolar, Jakub/0000-0002-0957-4380 FU National Cancer Institute [U24-CA76518]; National Heart Lung and Blood Institute; National Institute of Allergy and Infectious Diseases, Heath Resources and Services Administration [HHSH234200637015C]; intramural program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute FX Supported by a Public Health Service grant (U24-CA76518) from the National Cancer Institute, the National Heart Lung and Blood Institute and the National Institute of Allergy and Infectious Diseases, Heath Resources and Services Administration (HHSH234200637015C) and the intramural program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (S.M.G., B.P.A., N.G., P.S.R., and S.A.S.). The opinions, findings, and conclusions or recommendations expressed herein are those of the authors and do not reflect the views of the National Institutes of Health. NR 24 TC 28 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2013 VL 19 IS 8 BP 1238 EP 1243 DI 10.1016/j.bbmt.2013.05.021 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 194BW UT WOS:000322607000018 PM 23751955 ER PT J AU Radhakrishnan, H Srinivasan, VJ AF Radhakrishnan, Harsha Srinivasan, Vivek J. TI Compartment-resolved imaging of cortical functional hyperemia with OCT angiography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; SENSORY STIMULATION; BRAIN CORTEX; RAT-BRAIN; MICROSCOPY; MICROVASCULATURE; SIGNAL; DYNAMICS AB Optical Coherence Tomography (OCT) angiography was applied to image functional hyperemia in different vascular compartments in the rat somatosensory cortex. Dynamic backscattering changes, indicative of changes in dynamic red blood cell (dRBC) content, were used to monitor the hemodynamic response. Three-dimensional movies depicting the microvascular response to neuronal activation were created for the first time. An increase in the attenuation coefficient during activation was identified, and a simple normalization procedure was proposed to correct for it. This procedure was applied to determine compartment-resolved backscattering changes caused by dRBC content changes during functional activation. Increases in dRBC content were observed in all vascular compartments (arterial, arteriolar, capillary, and venular), with the largest responses found in the arterial and arteriolar compartments. dRBC content increased with dilation in arteries but with barely detectable dilation in veins. dRBC content increased in capillaries without significant "all or none" capillary recruitment. (C) 2013 Optical Society of America C1 [Radhakrishnan, Harsha; Srinivasan, Vivek J.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Radhakrishnan, Harsha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02129 USA. RP Radhakrishnan, H (reprint author), Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. EM vjsriniv@ucdavis.edu FU National Institutes of Health [R00NS067050, EB00790, EB001954 R01]; American Heart Association [11IRG5440002]; Glaucoma Research Foundation Catalyst for a Cure 2 FX We acknowledge support from the National Institutes of Health (R00NS067050, EB00790, and EB001954 R01), the American Heart Association (11IRG5440002), and the Glaucoma Research Foundation Catalyst for a Cure 2. We thank Weicheng Wu for the rat surgery and Bruce Rosen and Maria Angela Franceschini for general support. NR 44 TC 15 Z9 16 U1 0 U2 4 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 AUG 1 PY 2013 VL 4 IS 8 BP 1255 EP 1268 DI 10.1364/BOE.4.001255 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 194GL UT WOS:000322618900002 PM 24009990 ER PT J AU Fleming, CP Eckert, J Halpern, EF Gardecki, JA Tearney, GJ AF Fleming, Christine P. Eckert, Jocelyn Halpern, Elkan F. Gardecki, Joseph A. Tearney, Guillermo J. TI Depth resolved detection of lipid using spectroscopic optical coherence tomography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID ATHEROSCLEROTIC PLAQUES; RAMAN-SPECTROSCOPY; SCATTERING MEDIA; ABSORPTION; CHOLESTEROL; ATTENUATION; MICROSCOPY; MORPHOLOGY; PROFILES; COLLAGEN AB Optical frequency domain imaging (OFDI) can identify key components related to plaque vulnerability but can suffer from artifacts that could prevent accurate identification of lipid rich regions. In this paper, we present a model of depth resolved spectral analysis of OFDI data for improved detection of lipid. A quadratic Discriminant analysis model was developed based on phantom compositions known chemical mixtures and applied to a tissue phantom of a lipid-rich plaque. We demonstrate that a combined spectral and attenuation model can be used to predict the presence of lipid in OFDI images. (C) 2013 Optical Society of America C1 [Fleming, Christine P.] Columbia Univ, Dept Elect Engn, New York, NY 10027 USA. [Eckert, Jocelyn; Gardecki, Joseph A.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Fleming, CP (reprint author), Columbia Univ, Dept Elect Engn, New York, NY 10027 USA. EM cfleming@ee.columbia.edu RI Hendon, Christine/F-8261-2016 OI Hendon, Christine/0000-0001-7318-1517 FU National Institutes of Health [R01HL093717] FX The authors would like to thank Apostolos Doukas, Bill Farinelli, and Melissa Haskell for their technical help. The project was supported in part by the National Institutes of Health (R01HL093717, NIH Diversity Supplement Postdoctoral Fellowship, Loan Repayment Award). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart Lung and Blood Institute or the National Institutes of Health. NR 40 TC 32 Z9 32 U1 2 U2 11 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 AUG 1 PY 2013 VL 4 IS 8 BP 1269 EP 1284 DI 10.1364/BOE.4.001269 PG 16 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 194GL UT WOS:000322618900003 PM 24009991 ER PT J AU Perez-Nievas, BG Stein, TD Tai, HC Dols-Icardo, O Scotton, TC Barroeta-Espar, I Fernandez-Carballo, L de Munain, EL Perez, J Marquie, M Serrano-Pozo, A Frosch, MP Lowe, V Parisi, JE Petersen, RC Ikonomovic, MD Lopez, OL Klunk, W Hyman, BT Gomez-Isla, T AF Perez-Nievas, Beatriz G. Stein, Thor D. Tai, Hwan-Ching Dols-Icardo, Oriol Scotton, Thomas C. Barroeta-Espar, Isabel Fernandez-Carballo, Leticia de Munain, Estibaliz Lopez Perez, Jesus Marquie, Marta Serrano-Pozo, Alberto Frosch, Mathew P. Lowe, Val Parisi, Joseph E. Petersen, Ronald C. Ikonomovic, Milos D. Lopez, Oscar L. Klunk, William Hyman, Bradley T. Gomez-Isla, Teresa TI Dissecting phenotypic traits linked to human resilience to Alzheimer's pathology SO BRAIN LA English DT Article DE Alzheimers disease; amyloid pathology; tau pathology; resilience; astrocytes; microglia ID OLIGOMERIC AMYLOID-BETA; PITTSBURGH COMPOUND-B; TRANSGENIC MICE; NEURONAL LOSS; MOUSE MODEL; COGNITIVE IMPAIRMENT; APOLIPOPROTEIN E4; TAU OLIGOMERS; SYNAPSE LOSS; EARLY-LIFE AB Clinico-pathological correlation studies and positron emission tomography amyloid imaging studies have shown that some individuals can tolerate substantial amounts of Alzheimer's pathology in their brains without experiencing dementia. Few details are known about the neuropathological phenotype of these unique cases that might prove relevant to understanding human resilience to Alzheimer's pathology. We conducted detailed quantitative histopathological and biochemical assessments on brains from non-demented individuals before death whose brains were free of substantial Alzheimer's pathology, non-demented individuals before death but whose post-mortem examination demonstrated significant amounts of Alzheimer's changes ('mismatches'), and demented Alzheimer's cases. Quantification of amyloid-beta plaque burden, stereologically-based counts of neurofibrillary tangles, neurons and reactive glia, and morphological analyses of axons were performed in the multimodal association cortex lining the superior temporal sulcus. Levels of synaptic integrity markers, and soluble monomeric and multimeric amyloid-beta and tau species were measured. Our results indicate that some individuals can accumulate equivalent loads of amyloid-beta plaques and tangles to those found in demented Alzheimer's cases without experiencing dementia. Analyses revealed four main phenotypic differences among these two groups: (i) mismatches had striking preservation of neuron numbers, synaptic markers and axonal geometry compared to demented cases; (ii) demented cases had significantly higher burdens of fibrillar thioflavin-S-positive plaques and of oligomeric amyloid-beta deposits reactive to conformer-specific antibody NAB61 than mismatches; (iii) strong and selective accumulation of hyperphosphorylated soluble tau multimers into the synaptic compartment was noted in demented cases compared with controls but not in mismatches; and (iv) the robust glial activation accompanying amyloid-beta and tau pathologies in demented cases was remarkably reduced in mismatches. Further biochemical measurements of soluble amyloid-beta species-monomers, dimers and higher molecular weight oligomers-in total brain homogenates and synaptoneurosomal preparations failed to demonstrate significant differences between mismatches and demented cases. Together, these data suggest that amyloid-beta plaques and tangles do not inevitably result in neural system derangement and dementia in all individuals. We identified distinct phenotypic characteristics in the profile of brain fibrillar and soluble amyloid-beta and tau accrual and in the glial response that discriminated demented and non-demented individuals with high loads of Alzheimer's pathology. Amyloid-beta deposition in the form of fibrillar plaques and intimately related oligomeric amyloid-beta assemblies, hyperphosphorylated soluble tau species localized in synapses, and glial activation emerged in this series as likely mediators of neurotoxicity and altered cognition, providing further insight into factors and pathways potentially involved in human susceptibility or resilience to Alzheimer's pathological changes. C1 [Perez-Nievas, Beatriz G.; Stein, Thor D.; Tai, Hwan-Ching; Dols-Icardo, Oriol; Scotton, Thomas C.; Barroeta-Espar, Isabel; Fernandez-Carballo, Leticia; de Munain, Estibaliz Lopez; Perez, Jesus; Marquie, Marta; Serrano-Pozo, Alberto; Frosch, Mathew P.; Hyman, Bradley T.; Gomez-Isla, Teresa] Harvard Univ, Massachusetts Gen Hosp ADRC, Boston, MA 02115 USA. [Lowe, Val] Mayo Clin & Mayo Fdn, Dept Diagnost Radiol, Rochester, MN 55905 USA. [Parisi, Joseph E.] Mayo Clin, Rochester, MN USA. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Ikonomovic, Milos D.; Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst Pittsburgh, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Klunk, William] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Klunk, William] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Gomez-Isla, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, 15th Parkman St, Boston, MA 02114 USA. EM tgomezisla@partners.org OI Klunk, William/0000-0001-5512-0251; Stein, Thor/0000-0001-6954-4477; Dols Icardo, Oriol/0000-0003-2656-8748; TAI, HWAN-CHING/0000-0003-0668-9163; SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU NIH [U01 AG016976, AG005133]; Fundacion Alfonso Martin Escudero FX This project was funded in part by NIH grant (U01 AG016976 and AG005133). IBE is recipient of a scholarship from Fundacion Alfonso Martin Escudero. NR 61 TC 56 Z9 56 U1 3 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2013 VL 136 BP 2510 EP 2526 DI 10.1093/brain/awt171 PN 8 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 190KG UT WOS:000322338000022 PM 23824488 ER PT J AU Demirtas-Tatlidede, A Schmahmann, JD AF Demirtas-Tatlidede, Asli Schmahmann, Jeremy D. TI Morality: incomplete without the cerebellum? SO BRAIN LA English DT Letter ID COGNITIVE-AFFECTIVE SYNDROME; SPINOCEREBELLAR ATAXIA; FUNCTIONAL TOPOGRAPHY; DECISION-MAKING; EMPATHY; FMRI; MIND; EMOTION; OTHERS; NEUROANATOMY C1 [Demirtas-Tatlidede, Asli] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Behav Neurol & Movement Disorders Unit, Istanbul, Turkey. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Ataxia Unit, Cognit Behav Neurol Unit, Lab Neuroanat & Cerebellar Neurobiol,Dept Neurol, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, CPZS-340,175 Cambridge St, Boston, MA 02114 USA. EM jschmahmann@partners.org FU NIMH NIH HHS [R01 MH06044] NR 46 TC 2 Z9 2 U1 1 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2013 VL 136 DI 10.1093/brain/awt070 PN 8 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 190KG UT WOS:000322338000004 PM 23645927 ER PT J AU Nechuta, S Caan, BJ Chen, WY Kwan, ML Lu, W Cai, H Poole, EM Flatt, SW Zheng, W Pierce, JP Shu, XO AF Nechuta, Sarah Caan, Bette J. Chen, Wendy Y. Kwan, Marilyn L. Lu, Wei Cai, Hui Poole, Elizabeth M. Flatt, Shirley W. Zheng, Wei Pierce, John P. Shu, Xiao Ou TI Postdiagnosis Cruciferous Vegetable Consumption and Breast Cancer Outcomes: A Report from the After Breast Cancer Pooling Project SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RANDOMIZED-TRIAL; DIETARY PATTERN; LIVING WHEL; RISK; ISOTHIOCYANATES; CHEMOPREVENTION; INDOLE-3-CARBINOL; RECURRENCE; SURVIVAL; WOMEN AB Cruciferous vegetables are a major source of glucosinolate-derived bioactive compounds such as isothiocyanates, which have been shown in animal and in vitro studies to inhibit cancer growth and progression. Few studies have investigated cruciferous vegetable intake after diagnosis and breast cancer outcomes. Using data from the After Breast Cancer Pooling Project, which includes prospective data from U. S. and Chinese breast cancer survivors, we evaluated the association of cruciferous vegetables with breast cancer outcomes. Analyses included 11,390 women diagnosed with stage I-III invasive breast cancer (1990-2006) from four cohorts. Cruciferous vegetable intake (g/day) was assessed using food frequency questionnaires (mean of 22 months postdiagnosis). Study heterogeneity was evaluated by the Q statistic; hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using delayed-entry Cox regression models stratified by study. After a median follow-up of 9.0 years, 1,725 deaths and 1,421 recurrences were documented. In pooled analyses using study-specific quartiles, cruciferous vegetable intake was not associated with breast cancer outcomes, adjusting for known clinical prognostic factors and selected lifestyle factors. HRs (95% CIs) by increasing quartiles (reference = lowest quartile) were 1.08 (0.93-1.25), 1.01 (0.87-1.18), and 1.10 (0.95-1.28) for recurrence (P-trend = 0.34) and 1.01 (0.88-1.15), 0.97 (0.84-1.11), and 0.99 (0.86-1.13) for total mortality (P-trend = 0.84). No associations were observed for subgroups defined by estrogen receptor status, stage, or tamoxifen therapy. Cruciferous vegetable intake at approximately two years after diagnosis was not associated with recurrence or mortality. Our results do not support an association between postdiagnosis cruciferous vegetable intake and breast cancer outcomes. (C) 2013 AACR. C1 [Nechuta, Sarah; Cai, Hui; Zheng, Wei; Shu, Xiao Ou] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37203 USA. [Caan, Bette J.; Kwan, Marilyn L.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Flatt, Shirley W.; Pierce, John P.] Univ Calif San Diego, Moores UCSD Canc Ctr, Canc Prevent & Control Program, San Diego, CA 92103 USA. [Chen, Wendy Y.; Poole, Elizabeth M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lu, Wei] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China. RP Nechuta, S (reprint author), Vanderbilt Univ, Med Ctr, Epidemiol Ctr, Inst Med & Publ Hlth, 2525 West End Ave,Suite 300, Nashville, TN 37203 USA. EM sarah.nechuta@vanderbilt.edu FU National Cancer Institute at the NIH [3R01 CA118229-03S1]; National Institute of Environmental Health Sciences [5K12ES015855]; National Cancer Institute [T32 CA009001]; WHEL Study (Susan G. Komen Foundation) [KG100988]; LACE Study (National Cancer Institute) [R01 CA129059]; NHS [P01 CA87969]; SBCSS [Department of Defense Breast Cancer Research Program] [DAMD 17-02-1-0607]; SBCSS [National Cancer Institute] [R01 CA118229] FX This work was supported by the National Cancer Institute at the NIH (Grant number 3R01 CA118229-03S1). S. Nechuta was partly supported by grant 5K12ES015855 from the National Institute of Environmental Health Sciences. E. M. Poole was supported by grant T32 CA009001 from the National Cancer Institute. The parent grants for each individual cohort included are as follows: WHEL Study (Susan G. Komen Foundation, #KG100988), LACE Study (National Cancer Institute, R01 CA129059), NHS (P01 CA87969), SBCSS [Department of Defense Breast Cancer Research Program (DAMD 17-02-1-0607), and the National Cancer Institute (R01 CA118229)]. NR 25 TC 5 Z9 5 U1 3 U2 17 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 AUG PY 2013 VL 22 IS 8 BP 1451 EP 1456 DI 10.1158/1055-9965.EPI-13-0446 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 195NP UT WOS:000322710100011 PM 23765086 ER PT J AU Black, JC Manning, AL Van Rechem, C Kim, J Ladd, B Cho, J Pineda, CM Murphy, N Daniels, DL Montagna, C Lewis, PW Glass, K Allis, CD Dyson, NJ Getz, G Whetstine, JR AF Black, Joshua C. Manning, Amity L. Van Rechem, Capucine Kim, Jaegil Ladd, Brendon Cho, Juok Pineda, Cristiana M. Murphy, Nancy Daniels, Danette L. Montagna, Cristina Lewis, Peter W. Glass, Kimberly Allis, C. David Dyson, Nicholas J. Getz, Gad Whetstine, Johnathan R. TI KDM4A Lysine Demethylase Induces Site-Specific Copy Gain and Rereplication of Regions Amplified in Tumors SO CELL LA English DT Article ID REPLICATION ORIGINS; NUMBER ALTERATION; DRUG-RESISTANCE; FISSION YEAST; HUMAN CANCERS; CELLS; MECHANISMS; AMPLIFICATION; INSTABILITY; INHIBITION AB Acquired chromosomal instability and copy number alterations are hallmarks of cancer. Enzymes capable of promoting site-specific copy number changes have yet to be identified. Here, we demonstrate that H3K9/36me3 lysine demethylase KDM4A/JMJD2A overexpression leads to localized copy gain of 1q12, 1q21, and Xq13.1 without global chromosome instability. KDM4A-amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase, and is not stable but is regenerated each cell division. Sites with increased copy number are rereplicated and have increased KDM4A, MCM, and DNA polymerase occupancy. Suv39h1/KMT1A or HP1 gamma overexpression suppresses the copy gain, whereas H3K9/K36 methylation interference promotes gain. Our results demonstrate that overexpression of a chromatin modifier results in site-specific copy gains. This begins to establish how copy number changes could originate during tumorigenesis and demonstrates that transient overexpression of specific chromatin modulators could promote these events. C1 [Black, Joshua C.; Manning, Amity L.; Van Rechem, Capucine; Ladd, Brendon; Pineda, Cristiana M.; Dyson, Nicholas J.; Getz, Gad; Whetstine, Johnathan R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Black, Joshua C.; Manning, Amity L.; Van Rechem, Capucine; Ladd, Brendon; Pineda, Cristiana M.; Dyson, Nicholas J.; Whetstine, Johnathan R.] Harvard Univ, Dept Med, Sch Med, Charlestown, MA 02129 USA. [Getz, Gad] Harvard Univ, Dept Pathol, Sch Med, Charlestown, MA 02129 USA. [Kim, Jaegil; Cho, Juok; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Murphy, Nancy; Daniels, Danette L.] Promega Corp, Madison, WI 53711 USA. [Montagna, Cristina] Yeshiva Univ Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Lewis, Peter W.; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA. [Glass, Kimberly] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Glass, Kimberly] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Getz, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 13th St, Charlestown, MA 02129 USA. EM gadgetz@broadinstitute.org; jwhetstine@hms.harvard.edu RI Black, Joshua/Q-2484-2015; OI Lewis, Peter/0000-0002-9816-7823 FU Ellison Medical Foundation [CA059267, R01GM097360]; NIH [U24CA143845]; Jane Coffin Childs Memorial Fund for Medical Research; MGH ECOR Tosteson Postdoctoral Fellowship; CCSG [P30CA013330]; [R01CA155202] FX We are grateful to Ravi Mylvaganam and the MGH Flow Cytometry core for assistance with the cell sorting. We thank Mo Motamedi for helpful comments on the manuscript. This work was supported by funding to J.R.W. from the Ellison Medical Foundation, CA059267 and R01GM097360. G.G. and J.K. are supported by NIH U24CA143845. J.C.B. was a Fellow of The Jane Coffin Childs Memorial Fund for Medical Research. This investigation has been aided by a grant from The Jane Coffin Childs Memorial Fund for Medical Research. N.J.D. is supported by R01CA155202. A.L.M. is supported by MGH ECOR Tosteson Postdoctoral Fellowship. C.M. is supported by CCSG P30CA013330. NR 39 TC 72 Z9 73 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD AUG 1 PY 2013 VL 154 IS 3 BP 541 EP 555 DI 10.1016/j.cell.2013.06.051 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 194JY UT WOS:000322629900009 PM 23871696 ER PT J AU Anand, P Brown, JD Lin, CY Qi, J Zhang, RL Artero, PC Alaiti, MA Bullard, J Alazem, K Margulies, KB Cappola, TP Lemieux, M Plutzky, J Bradner, JE Haldar, SM AF Anand, Priti Brown, Jonathan D. Lin, Charles Y. Qi, Jun Zhang, Rongli Artero, Pedro Calderon Alaiti, M. Amer Bullard, Jace Alazem, Kareem Margulies, Kenneth B. Cappola, Thomas P. Lemieux, Madeleine Plutzky, Jorge Bradner, James E. Haldar, Saptarsi M. TI BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure SO CELL LA English DT Article ID ELONGATION-FACTOR-B; CARDIAC-HYPERTROPHY; P-TEFB; C-MYC; SELECTIVE-INHIBITION; GENE-EXPRESSION; PROTEIN BRD4; IN-VIVO; DISEASE; STRESS AB Heart failure (HF) is driven by the interplay between regulatory transcription factors and dynamic alterations in chromatin structure. Pathologic gene trans-activation in HF is associated with recruitment of histone acetyl-transferases and local chromatin hyperacetylation. We therefore assessed the role of acetyl-lysine reader proteins, or bromodomains, in HF. Using a chemical genetic approach, we establish a central role for BET family bromodomain proteins in gene control during HF pathogenesis. BET inhibition potently suppresses cardiomyocyte hypertrophy in vitro and pathologic cardiac remodeling in vivo. Integrative transcriptional and epigenomic analyses reveal that BET proteins function mechanistically as pause-release factors critical to expression of genes that are central to HF pathogenesis and relevant to the pathobiology of failing human hearts. This study implicates epigenetic readers as essential effectors of transcriptional pause release during HF pathogenesis and identifies BET coactivator proteins as therapeutic targets in the heart. C1 [Anand, Priti; Zhang, Rongli; Artero, Pedro Calderon; Alaiti, M. Amer; Bullard, Jace; Alazem, Kareem; Haldar, Saptarsi M.] Case Western Reserve Univ, Case Cardiovasc Res Inst, Dept Med, Sch Med, Cleveland, OH 44106 USA. [Anand, Priti; Zhang, Rongli; Artero, Pedro Calderon; Alaiti, M. Amer; Bullard, Jace; Alazem, Kareem; Haldar, Saptarsi M.] Univ Hosp Case Med Ctr, Harrington Heart & Vasc Inst, Cleveland, OH 44106 USA. [Brown, Jonathan D.; Plutzky, Jorge] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Lin, Charles Y.; Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Margulies, Kenneth B.; Cappola, Thomas P.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. [Lemieux, Madeleine] Bioinfo, Plantagenet, ON K0B 1L0, Canada. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu; saptarsi.haldar@case.edu OI Lemieux, Madeleine/0000-0001-6355-8691 FU Individual Biomedical Research Award from The Hartwell Foundation; Visconsi Research Scholars Fund [NIH-K08 CA128972]; Burroughs-Wellcome Fund; Damon-Runyon Cancer Research Foundation; Richard and Susan Smith Family Foundation; Next Generation Award; U.S. Department of Defense [NIH-T32 HL105338, NIH-R01 HL105993, NIH-K08 HL105678]; [NIH-R01 DK093821]; [NIH-K08 HL086614] FX We are grateful to R. Young and P. Rahl for stimulating discussions; M. Berkeley and the late E. Fox (DFCI Microarray Core) for assistance with microarray experiments; Avery Whitlock for illustrations; and Tom Volkert, Jennifer Love, and Sumeet Gupta at the Whitehead Genome Core for assistance with genome sequencing. This research was supported by an NIH-R01 DK093821 and NIH-K08 HL086614, Individual Biomedical Research Award from The Hartwell Foundation, and the Visconsi Research Scholars Fund (S.M.H.); NIH-K08 CA128972, the Burroughs-Wellcome Fund, the Damon-Runyon Cancer Research Foundation, the Richard and Susan Smith Family Foundation, and the Next Generation Award (J.E.B.); U.S. Department of Defense (C.Y.L.); NIH-T32 HL105338 (M.A.A.); NIH-R01 HL105993 (K.B. M. and T.P.C); and NIH-K08 HL105678 (J.D.B.). Dr. Bradner is the scientific founder of Tensha Therapeutics, which is clinically translating drug-like derivatives of the JQ1 chemical probe of BET bromodomains used in this study, as cancer therapeutics. As such, the Dana-Farber Cancer Institute and Dr. Bradner have been granted minority equity in Tensha. NR 51 TC 94 Z9 94 U1 5 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD AUG 1 PY 2013 VL 154 IS 3 BP 569 EP 582 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 194JY UT WOS:000322629900011 PM 23911322 ER PT J AU Stuart, LM Boyer, L AF Stuart, Lynda M. Boyer, Laurent TI RhoGTPases - NODes for effector-triggered immunity in animals SO CELL RESEARCH LA English DT Editorial Material ID RHO-GTPASES; INNATE IMMUNITY; ACTIVATION AB A recent study published in Nature by Keestra and colleagues addresses how the immune system detects the pathogenic potential of microbes and provides evidence that one strategy involves NOD1, which monitors the activation state of the RhoGTPases that are targeted by virulence effectors produced by pathogenic microbes. Interestingly, their findings reveal striking similarities with previous observations made in flies and plants, establishing the evolutionary conservation of this detection system in the innate immune arsenal in many taxa. C1 [Stuart, Lynda M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Stuart, Lynda M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Stuart, Lynda M.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Boyer, Laurent] Ctr Mediterraneen Med Mol, INSERM, U1065, C3M, F-06204 Nice, France. RP Stuart, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM lstuart@partners.org RI Boyer, laurent/F-8921-2015 OI Boyer, laurent/0000-0002-1375-1706 FU NIDDK NIH HHS [P30 DK043351] NR 10 TC 3 Z9 3 U1 1 U2 6 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD AUG PY 2013 VL 23 IS 8 BP 980 EP 981 DI 10.1038/cr.2013.68 PG 2 WC Cell Biology SC Cell Biology GA 193QD UT WOS:000322574900004 PM 23689278 ER PT J AU Boronat, S Newberry, P Mehan, W Thiele, EA Duhaime, AC AF Boronat, Susana Newberry, Peter Mehan, William Thiele, Elizabeth Anne Duhaime, Ann-Christine TI Kluver-Bucy syndrome after unilateral frontotemporal resection in a child with tuberous sclerosis SO CHILDS NERVOUS SYSTEM LA English DT Article DE Tuberous sclerosis complex; Pediatric; Kluver-Bucy syndrome; Epilepsy surgery; Behavior ID EPILEPSY AB Kluver-Bucy syndrome (KBS) is a behavioral phenotype that appears most often after bilateral temporal damage. The main features of KBS are compulsion to examine objects orally, increased sexual activity, placidity, hypermetamorphosis (irresistible impulse to notice and react to everything within sight), visual agnosia, and problems with memory. It is more rarely reported in children than in adults. We present a case of KBS in a 2-year-old boy with tuberous sclerosis complex (TSC) after left frontotemporal resection for refractory epilepsy. This is the first KBS after unilateral temporal resection in a child, although it has already been reported in two adult cases. It also is the first case reported in a TSC patient. C1 [Boronat, Susana; Thiele, Elizabeth Anne] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Newberry, Peter] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mehan, William] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Boronat, Susana] Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Pediat Neurol, E-08193 Barcelona, Spain. [Boronat, Susana] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. RP Boronat, S (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM susboronat@gmail.com NR 15 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0256-7040 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD AUG PY 2013 VL 29 IS 8 BP 1391 EP 1394 DI 10.1007/s00381-013-2127-3 PG 4 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 185FT UT WOS:000321952500029 PM 23636147 ER PT J AU Zhang, Y Schnabel, CA Schroeder, BE Jerevall, PL Jankowitz, RC Fornander, T Stal, O Brufsky, AM Sgroi, D Erlander, MG AF Zhang, Yi Schnabel, Catherine A. Schroeder, Brock E. Jerevall, Piiha-Lotta Jankowitz, Rachel C. Fornander, Tommy Stal, Olle Brufsky, Adam M. Sgroi, Dennis Erlander, Mark G. TI Breast Cancer Index Identifies Early-Stage Estrogen Receptor-Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION SIGNATURES; MOLECULAR GRADE INDEX; ADJUVANT TAMOXIFEN; RANDOMIZED-TRIAL; PROGNOSTIC SIGNATURE; STOCKHOLM TRIAL; LETROZOLE; THERAPY; UTILITY; WOMEN AB Purpose: Residual risk of relapse remains a substantial concern for patients with hormone receptor-positive breast cancer, with approximately half of all disease recurrences occurring after five years of adjuvant antiestrogen therapy. Experimental Design: The objective of this study was to examine the prognostic performance of an optimized model of Breast Cancer Index (BCI), an algorithmic gene expression-based signature, for prediction of early (0-5 years) and late (>5 years) risk of distant recurrence in patients with estrogen receptor-positive (ER+), lymph node-negative (LN-) tumors. The BCI model was validated by retrospective analyses of tumor samples from tamoxifen-treated patients from a randomized prospective trial (Stockholm TAM, n = 317) and a multi-institutional cohort (n = 358). Results: Within the Stockholm TAM cohort, BCI risk groups stratified the majority (similar to 65%) of patients as low risk with less than 3% distant recurrence rate for 0 to 5 years and 5 to 10 years. In the multi-institutional cohort, which had larger tumors, 55% of patients were classified as BCI low risk with less than 5% distant recurrence rate for 0 to 5 years and 5 to 10 years. For both cohorts, continuous BCI was the most significant prognostic factor beyond standard clinicopathologic factors for 0 to 5 years and more than five years. Conclusions: The prognostic sustainability of BCI to assess early- and late-distant recurrence risk at diagnosis has clinical use for decisions of chemotherapy at diagnosis and for decisions for extended adjuvant endocrine therapy beyond five years. (C) 2013 AACR. C1 [Zhang, Yi; Schnabel, Catherine A.; Schroeder, Brock E.; Erlander, Mark G.] BioTheranostics Inc, San Diego, CA 92121 USA. [Jerevall, Piiha-Lotta; Sgroi, Dennis] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Jankowitz, Rachel C.; Brufsky, Adam M.] Univ Pittsburgh, Med Ctr, Div Hematol Oncol, Pittsburgh, PA USA. [Fornander, Tommy] Karolinska Inst, Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Stal, Olle] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. [Stal, Olle] Cty Council Ostergotland, Dept Oncol, Linkoping, Sweden. RP Erlander, MG (reprint author), BioTheranostics Inc, 9640 Towne Ctr Dr,Ste 200, San Diego, CA 92121 USA. EM Mark.erlander@biotheranostics.com FU Avon Foundation; NIH/National Cancer Institute; U.S. Department of Defense [BC097711]; Susan G. Komen for the Cure FX This work was supported in part by Avon Foundation (to D. Sgroi), NIH/National Cancer Institute (to D. Sgroi), The U.S. Department of Defense Breast Cancer Award BC097711 (to D. Sgroi), and The Susan G. Komen for the Cure (to D. Sgroi). NR 26 TC 46 Z9 50 U1 0 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 AUG 1 PY 2013 VL 19 IS 15 BP 4196 EP 4205 DI 10.1158/1078-0432.CCR-13-0804 PG 10 WC Oncology SC Oncology GA 193ZB UT WOS:000322598900019 PM 23757354 ER PT J AU Slingluff, CL Lee, S Zhao, FM Chianese-Bullock, KA Olson, WC Butterfield, LH Whiteside, TL Leming, PD Kirkwood, JM AF Slingluff, Craig L., Jr. Lee, Sandra Zhao, Fengmin Chianese-Bullock, Kimberly A. Olson, Walter C. Butterfield, Lisa H. Whiteside, Theresa L. Leming, Philip D. Kirkwood, John M. TI A Randomized Phase II Trial of Multiepitope Vaccination with Melanoma Peptides for Cytotoxic T Cells and Helper T Cells for Patients with Metastatic Melanoma (E1602) SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; PARAFFIN-EMBEDDED PRIMARY; IN-VIVO; CELLULAR IMMUNOTHERAPY; COOPERATIVE GROUP; PROSTATE-CANCER; TUMOR-ANTIGENS; LYMPHOCYTES-T; SIPULEUCEL-T; LYMPH-NODE AB Purpose: This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T lymphocyte (CTL) responses to a melanoma vaccine and improve clinical outcome in patients with advanced melanoma. Experimental Design: One hundred seventy-five patients with measurable stage IV melanoma were enrolled into 4 treatment groups, vaccinated with 12 MHC class I-restricted melanoma peptides to stimulate CTL (12MP, group A), plus a tetanus peptide (group B), or a mixture of 6 melanoma helper peptides (6MHP, group C) to stimulate helper T lymphocytes (HTL), or with 6 melanoma helper peptide (6MHP) alone (group D), in incomplete Freund's adjuvant plus granulocyte macrophage colony-stimulating factor. CTL responses were assessed using an in vitro-stimulated IFN-gamma ELIspot assay, and HTL responses were assessed using a proliferation assay. Results: In groups A to D, respectively, CTL response rates to 12 melanoma peptides were 43%, 47%, 28%, and 5%, and HTL response rates to 6MHP were in 3%, 0%, 40%, and 41%. Best clinical response was partial response in 7 of 148 evaluable patients (4.7%) without significant difference among study arms. Median overall survival (OS) was 11.8 months. Immune response to 6 MHP was significantly associated with both clinical response (P = 0.036) and OS (P = 0.004). Conclusion: Each vaccine regimen was immunogenic, but MHPs did not augment CTL responses to 12 melanoma peptides. The association of survival and immune response to 6MHP supports further investigation of helper peptide vaccines. For patients with advanced melanoma, multipeptide vaccines should be studied in combination with other potentially synergistic active therapies. (C) 2013 AACR. C1 [Slingluff, Craig L., Jr.; Chianese-Bullock, Kimberly A.; Olson, Walter C.] Univ Virginia, Human Immune Therapy Ctr, Dept Surg, Charlottesville, VA 22908 USA. [Lee, Sandra; Zhao, Fengmin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Butterfield, Lisa H.; Whiteside, Theresa L.; Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Leming, Philip D.] Christ Hosp, Cincinnati, OH 45219 USA. RP Slingluff, CL (reprint author), Univ Virginia, Human Immune Therapy Ctr, Dept Surg, 1352 Jordan Hall,POB 801457, Charlottesville, VA 22908 USA. EM cls8h@virginia.edu FU Eastern Cooperative Oncology Group (ECOG); Public Health Service from the National Cancer Institute, NIH [CA23318, CA66636, CA21115, CA49957, CA39229, CA104362]; Department of Health and Human Services; NIH/NCI [NIH R01 CA118386]; University of Virginia Cancer Center [NIH/NCI P30 CA44579]; UVA General Clinical Research Center [NIH M01 RR00847]; Frontier Science and Technology Research Foundation FX This study was supported by the Eastern Cooperative Oncology Group (ECOG; Principal investigator and Director of ECOG: Robert L. Comis) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA49957, CA39229, and CA104362 from the National Cancer Institute, NIH, and the Department of Health and Human Services. This study was also supported in part by NIH/NCI grant NIH R01 CA118386 (to C.L. Slingluff), by the University of Virginia Cancer Center Support Grant (NIH/NCI P30 CA44579: Clinical Trials Office, Biorepository and Tissue Research Facility, Flow Cytometry Core, and Biomolecular Core Facility); and the UVA General Clinical Research Center (NIH M01 RR00847). The ECOG Central Immunology Laboratory is supported by Frontier Science and Technology Research Foundation. GM-CSF used in the vaccine adjuvant was provided by Berlex/Genzyme. Peptides used in this vaccine were prepared with philanthropic support from the Commonwealth Foundation for Cancer Research and Alice and Bill Goodwin. Additional philanthropic support was provided by Frank and Jane Batten, the James and Rebecca Craig Foundation, George S. Suddock, Richard and Sherry Sharp, and the Patients and Friends Research Fund of the University of Virginia Cancer Center. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute managed distribution of the vaccine preparations and adjuvant to participating centers. NR 49 TC 24 Z9 24 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2013 VL 19 IS 15 BP 4228 EP 4238 DI 10.1158/1078-0432.CCR-13-0002 PG 11 WC Oncology SC Oncology GA 193ZB UT WOS:000322598900022 PM 23653149 ER PT J AU Gainor, JF Varghese, AM Ou, SHI Kabraji, S Awad, MM Katayama, R Pawlak, A Mino-Kenudson, M Yeap, BY Riely, GJ Iafrate, AJ Arcila, ME Ladanyi, M Engelman, JA Dias-Santagata, D Shaw, AT AF Gainor, Justin F. Varghese, Anna M. Ou, Sai-Hong Ignatius Kabraji, Sheheryar Awad, Mark M. Katayama, Ryohei Pawlak, Amanda Mino-Kenudson, Mari Yeap, Beow Y. Riely, Gregory J. Iafrate, A. John Arcila, Maria E. Ladanyi, Marc Engelman, Jeffrey A. Dias-Santagata, Dora Shaw, Alice T. TI ALK Rearrangements Are Mutually Exclusive with Mutations in EGFR or KRAS: An Analysis of 1,683 Patients with Non-Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID EML4-ALK FUSION GENE; CRIZOTINIB RESISTANCE; KINASE INHIBITORS; ADENOCARCINOMAS; FEATURES; IDENTIFICATION; GEFITINIB; ERLOTINIB; THERAPY; TUMORS AB Purpose: Anaplastic lymphoma kinase (ALK) gene rearrangements define a distinct molecular subset of non-small cell lung cancer (NSCLC). Recently, several case reports and small series have reported that ALK rearrangements can overlap with other oncogenic drivers in NSCLC in crizotinib-naive and crizotinib-resistant cancers. Experimental Design: We reviewed clinical genotyping data from 1,683 patients with NSCLC and investigated the prevalence of concomitant EGFR or KRAS mutations among patients with ALK-positive NSCLC. We also examined biopsy specimens from 34 patients with ALK-positive NSCLC after the development of resistance to crizotinib. Results: Screening identified 301 (17.8%) EGFR mutations, 465 (27.6%) KRAS mutations, and 75 (4.4%) ALK rearrangements. EGFR mutations and ALK rearrangements were mutually exclusive. Four patients with KRAS mutations were found to have abnormal ALK FISH patterns, most commonly involving isolated 5' green probes. Sufficient tissue was available for confirmatory ALK immunohistochemistry in 3 cases, all of which were negative for ALK expression. Among patients with ALK-positive NSCLC who acquired resistance to crizotinib, repeat biopsy specimens were ALK FISH positive in 29 of 29 (100%) cases. Secondary mutations in the ALK kinase domain and ALK gene amplification were observed in 7 of 34 (20.6%) and 3 of 29 (10.3%) cases, respectively. No EGFR or KRAS mutations were identified among any of the 25 crizotinib-resistant, ALK-positive patients with sufficient tissue for testing. Conclusions: Functional ALK rearrangements were mutually exclusive with EGFR and KRAS mutations in a large Western patient population. This lack of overlap was also observed in ALK-positive cancers with acquired resistance to crizotinib. (C)2013 AACR. C1 [Gainor, Justin F.; Kabraji, Sheheryar; Awad, Mark M.; Katayama, Ryohei; Yeap, Beow Y.; Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pawlak, Amanda; Mino-Kenudson, Mari; Iafrate, A. John; Dias-Santagata, Dora] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Varghese, Anna M.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Arcila, Maria E.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Ou, Sai-Hong Ignatius] Univ Calif Irvine, Dept Med, Orange, CA 92668 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, 32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org OI Varghese, Anna/0000-0001-5426-0885 FU U.S. NIH [5R01CA164273-02, 5P50CA090578-10]; V Foundation Translational Research Grant FX This work was supported by grants from the U.S. NIH 5R01CA164273-02 and 5P50CA090578-10, and by a V Foundation Translational Research Grant. NR 42 TC 149 Z9 154 U1 1 U2 17 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 AUG 1 PY 2013 VL 19 IS 15 BP 4273 EP 4281 DI 10.1158/1078-0432.CCR-13-0318 PG 9 WC Oncology SC Oncology GA 193ZB UT WOS:000322598900026 PM 23729361 ER PT J AU McCaffery, I Tudor, Y Deng, HJ Tang, R Suzuki, S Badola, S Kindler, HL Fuchs, CS Loh, E Patterson, SD Chen, L Gansert, JL AF McCaffery, Ian Tudor, Yanyan Deng, Hongjie Tang, Rui Suzuki, Samuel Badola, Sunita Kindler, Hedy L. Fuchs, Charles S. Loh, Elwyn Patterson, Scott D. Chen, Li Gansert, Jennifer L. TI Putative Predictive Biomarkers of Survival in Patients with Metastatic Pancreatic Adenocarcinoma Treated with Gemcitabine and Ganitumab, an IGF1R Inhibitor SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-I; CANCER RISK; FACTOR RECEPTOR; BINDING PROTEIN-3; PLASMA-LEVELS; AMG 479; INSULIN; SERUM; PTEN; LUNG AB Purpose: This planned exploratory analysis assessed the predictive nature of baseline circulating factors of the insulin-like growth factor (IGF) axis on the treatment effect of ganitumab (monoclonal antibody inhibitor of IGF-1 receptor) plus gemcitabine in a randomized phase II study in metastatic pancreatic adenocarcinoma. Experimental Design: Baseline levels of IGFs/IGF binding proteins (IGFBP) were analyzed in serum or plasma. Mutations and gene expression were analyzed in archival samples. Treatment effects between biomarker subgroups were compared for overall survival (OS). Associations of tumor markers with OS were evaluated. Results: For patients with evaluable samples, ganitumab was associated with improved OS versus placebo (HR, 0.49; 95% CI: 0.28-0.87). The treatment effect on improved OS was strong in the patient subset with higher levels of IGF-1, IGF-2, or IGFBP-3, or lower levels of IGFBP-2, but not so on the other corresponding subset. Median OS of ganitumab versus placebo in patients with higher levels of IGF-1, IGF-2, and IGFBP-3 was 16 versus 6.8 months (HR, 0.25; 95% CI: 0.09-0.67), 16 versus 5.9 months (HR, 0.24; 95% CI: 0.09-0.68), and 16 versus 6.8 months (HR, 0.28; 95% CI: 0.11-0.73), and in patients with lower IGFBP-2 levels was 12.7 versus 6.6 months (HR, 0.19; 95% CI: 0.07-0.55). Interaction between treatment and IGFs/IGFBPs in multivariate analyses suggested predictive potential for IGF-2 (P = 0.002) and IGFBP-2 (P = 0.02). KRAS mutation status and PTEN expression were not associated with OS. Conclusions: Baseline circulating factors of the IGF axis may predict OS benefit from ganitumab plus gemcitabine in metastatic pancreatic adenocarcinoma. (C)2013 AACR. C1 [McCaffery, Ian; Tudor, Yanyan; Deng, Hongjie; Tang, Rui; Patterson, Scott D.; Chen, Li; Gansert, Jennifer L.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Suzuki, Samuel; Loh, Elwyn] Amgen Inc, San Francisco, CA USA. [Badola, Sunita] Amgen Inc, Cambridge, England. [Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kindler, Hedy L.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP McCaffery, I (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. EM mccaffery.ian@gene.com FU Amgen Inc. FX The study was funded by Amgen Inc. NR 30 TC 28 Z9 29 U1 0 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 AUG 1 PY 2013 VL 19 IS 15 BP 4282 EP 4289 DI 10.1158/1078-0432.CCR-12-1840 PG 8 WC Oncology SC Oncology GA 193ZB UT WOS:000322598900027 PM 23741071 ER PT J AU Raab, PA Mackintosh, MA Gros, DF Morland, LA AF Raab, Phillip A. Mackintosh, Margaret-Anne Gros, Daniel F. Morland, Leslie A. TI Influence of Depression on State and Trait Anger in Veterans with Posttraumatic Stress Disorder SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Posttraumatic stress disorder; Anger; Major depressive disorder; Numbing; Dysphoria ID ADMINISTERED PTSD SCALE; COMBAT VETERANS; AGGRESSION; SYMPTOMS; HOSTILITY; SPECIFICITY; COMORBIDITY; THERAPY; ANXIETY; TRIAL AB Anger is one of the most important symptoms of posttraumatic stress disorder (PTSD), and is associated with many of the adverse correlates of PTSD. Researchers have proposed theories to explain the relationship between anger and PTSD, but no study to date has examined the mediating role of depression. The purpose of this study was to explore the mediating effects of current major depression disorder (MDD), as well as PTSD numbing and dysphoria symptom clusters (King et al. 1998; Simms et al. 2002) on the relationship between PTSD and anger. There were 98 participants in the study, and all were male veterans with combat-related PTSD taking part in a clinical trial. Results indicated that MDD partially mediated the relationship between PTSD and state anger, while numbing and dysphoria clusters partially mediated the relationships between other PTSD symptom clusters and trait anger. Implications for the treatment of anger in veterans with PTSD are discussed. C1 [Raab, Phillip A.; Mackintosh, Margaret-Anne; Morland, Leslie A.] Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs Pacific Isl Healthcare Syst, Pacific Isl Div, Honolulu, HI 96819 USA. [Raab, Phillip A.; Mackintosh, Margaret-Anne; Morland, Leslie A.] Pacific Hlth Res & Educ Inst, Honolulu, HI USA. [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC 29425 USA. [Morland, Leslie A.] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Raab, PA (reprint author), Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs Pacific Isl Healthcare Syst, Pacific Isl Div, 3375 Koapaka,Suite I-560, Honolulu, HI 96819 USA. EM drewraab@gmail.com OI Mackintosh, Margaret-Anne/0000-0002-2725-3177 NR 39 TC 2 Z9 2 U1 2 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD AUG PY 2013 VL 37 IS 4 BP 673 EP 679 DI 10.1007/s10608-012-9506-z PG 7 WC Psychology, Clinical SC Psychology GA 189MU UT WOS:000322272100002 ER PT J AU Alert, MD Rastegar, S Foret, M Slipp, L Jacquart, J Macklin, E Baim, M Fricchione, G Benson, H Denninger, J Yeung, A AF Alert, Marissa D. Rastegar, Sarah Foret, Megan Slipp, Lauren Jacquart, Jolene Macklin, Eric Baim, Margaret Fricchione, Gregory Benson, Herbert Denninger, John Yeung, Albert TI The effectiveness of a comprehensive mind body weight loss intervention for overweight and obese adults: A pilot study SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Article DE Obesity; Overweight; Mind body intervention behavioral intervention; Relaxation Response; Meditation ID QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; WOMEN; METABOLISM; STATEMENT; NUTRITION; BEHAVIOR; COUNCIL; STRESS AB Objectives: This pilot study evaluated the effectiveness of a comprehensive mind body intervention for weight loss in overweight and obesity and the maintenance of weight loss at 6-month follow-up. Design: Thirty-one overweight and obese employees (Body Mass Index (BMI) 28.6-47.9 kg/m(2)) from a large corporation participated in a 20-week comprehensive mind body intervention targeting weight loss. Main outcome measures: Weight, BMI, waist and hip circumference, rate pressure product (RPP), blood pressure, fasting blood glucose, cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and psychological variables were collected at baseline, post-intervention, and 6-month follow-up. Results: Using linear mixed model analyses, the intervention resulted in significant mean weight loss (-4.3 kg, 95% CI -5.8 to -2.8), decreases in BMI (-1.51, 95% CI -2.1 to -1.0), hip circumference measurement (-4.3 cm, 95% CI -6.9 to -1.5), and triglyceride levels (95% CI -33.1 to -4.8). In 6-month follow-up after intervention, statistically significant improvements in weight, BMI and waist measurement were sustained. Participants also showed positive changes in self-reported psychological indices: food-related disinhibition, and hunger both decreased significantly (p < 0.01); general self-efficacy increased (p < 0.05); positive affect increased (p < 0.001); physical function and self-esteem increased (p < 0.01); and measures of health-promoting behaviors on 4 subscales (health responsibility, physical activity, nutrition, and stress management) also showed statistically significant improvements (p < 0.001) at post-intervention and 6-month follow-up. Conclusions: This comprehensive mind body intervention showed modest effects on physical, laboratory, and psychological outcomes, both immediately following treatment and at 6-month follow-up, in overweight and obese individuals. (c) 2013 Elsevier Ltd. All rights reserved. C1 [Alert, Marissa D.; Rastegar, Sarah; Foret, Megan; Slipp, Lauren; Jacquart, Jolene; Macklin, Eric; Baim, Margaret; Fricchione, Gregory; Benson, Herbert; Denninger, John; Yeung, Albert] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02143 USA. [Yeung, Albert] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, 1 Bowdoin Sq, Boston, MA 02114 USA. EM ayeung@partners.org OI Macklin, Eric/0000-0003-1618-3502 FU Nutrition & Health Partnership Inc; Centers for Disease Control and Prevention [5R01DP000339] FX The study was supported by the non-profit organization Nutrition & Health Partnership Inc. Researchers' time was funded by Centers for Disease Control and Prevention, Grant Number 5R01DP000339. NR 23 TC 3 Z9 4 U1 1 U2 17 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0965-2299 J9 COMPLEMENT THER MED JI Complement. Ther. Med. PD AUG PY 2013 VL 21 IS 4 BP 286 EP 293 DI 10.1016/j.ctim.2013.05.005 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 194BX UT WOS:000322607100002 PM 23876558 ER PT J AU Pellicer, DL Sadow, PM Stephen, A Faquin, WC AF Pellicer, Daniel L. Sadow, Peter M. Stephen, Antonia Faquin, William C. TI Atypical squamous metaplasia in a benign cystic thyroid nodule mimicking high-grade carcinoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE thyroid; FNAB; squamous metaplasia; cyst; follicular adenoma ID NEEDLE-ASPIRATION BIOPSY; HASHIMOTOS THYROIDITIS; CYTOLOGY; APPRAISAL; CELLS; GLAND AB Squamous metaplasia (SM) occurs in a variety of thyroid conditions, both neoplastic and non-neoplastic. In a small subset of benign thyroid lesions, SM can create a diagnostic pitfall by mimicking a malignant process. Here, we describe the case of a 52-year-old male with a 1.5 cm right thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy showed markedly atypical, mitotically active epithelial cells which were suspicious for high-grade carcinoma. Resection of the nodule demonstrated a follicular adenoma with cystic changes and atypical SM of the cyst-lining component. As illustrated here, SM of the thyroid represents an important diagnostic pitfall for the cytopathologist, and should be included in the differential diagnosis of thyroid nodules, particularly those with potentially benign cystic changes. Diagn. Cytopathol. 2013;41:706-709. (c) 2013 Wiley Periodicals, Inc. C1 [Pellicer, Daniel L.; Sadow, Peter M.; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pellicer, Daniel L.; Sadow, Peter M.; Stephen, Antonia; Faquin, William C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Stephen, Antonia] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org NR 20 TC 3 Z9 3 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD AUG PY 2013 VL 41 IS 8 BP 706 EP 709 DI 10.1002/dc.22803 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 185ZT UT WOS:000322011400008 PM 22144088 ER PT J AU Kaunitz, JD Akiba, Y AF Kaunitz, Jonathan D. Akiba, Yasutada TI Wireless Telemetry and Cystic Fibrosis: Just the pHacts SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID PH C1 [Kaunitz, Jonathan D.; Akiba, Yasutada] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] West Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), West Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01 DK054221] NR 6 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2013 VL 58 IS 8 BP 2129 EP 2130 DI 10.1007/s10620-013-2714-x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 194RR UT WOS:000322650900002 PM 23748712 ER PT J AU Sauk, J Coron, E Kava, L Suter, M Gora, M Gallagher, K Rosenberg, M Ananthakrishnan, A Nishioka, N Lauwers, G Woods, K Brugge, W Forcione, D Bouma, BE Tearney, G AF Sauk, Jenny Coron, Emmanuel Kava, Lauren Suter, Melissa Gora, Michalina Gallagher, Kevin Rosenberg, Mireille Ananthakrishnan, Ashwin Nishioka, Norman Lauwers, Gregory Woods, Kevin Brugge, William Forcione, David Bouma, Brett E. Tearney, Guillermo TI Interobserver Agreement for the Detection of Barrett's Esophagus with Optical Frequency Domain Imaging SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Barrett's esophagus; Optical coherence tomography; Imaging/innovation; Upper endoscopy GI tract ID COHERENCE TOMOGRAPHY; INTESTINAL METAPLASIA; IN-VIVO; ADENOCARCINOMA; MICROSCOPY; ENDOMICROSCOPY; DYSPLASIA; BIOPSIES AB Optical frequency domain imaging (OFDI) is a second-generation form of optical coherence tomography (OCT) providing comprehensive cross-sectional views of the distal esophagus at a resolution of similar to 7 mu m. Using validated OCT criteria for squamous mucosa, gastric cardia mucosa, and Barrett's esophagus (BE), the objective of this study was to determine the inter- and intra-observer agreements by a large number of OFDI readers for differentiating these tissues. OFDI images were obtained from nine subjects undergoing screening and surveillance for BE. Sixty-four OFDI image regions of interest were randomly selected for review. A training set of 19 images was compiled distinguishing squamous mucosa from gastric cardia and BE using previously validated OCT criteria. The ten readers then interpreted images in a test set of 45 different images of squamous mucosa (n = 15), gastric cardia (n = 15), or BE (n = 15). Interobserver agreement differentiating the three tissue types and BE versus non-BE mucosa was determined using multi-rater Fleiss's kappa value. The images were later randomized again and four readers repeated the test 3 weeks later to assess intraobserver reliability. All ten readers showed excellent agreement for the differentiation of BE versus non-BE mucosa (kappa = 0.811 p < 0.0001) and for differentiating BE versus gastric cardia versus squamous mucosa (kappa = 0.866, p < 0.0001). For the four readers who repeated the test, the median intraobserver agreement (BE vs. non-BE) was high (kappa = 0.975, IQR: 0.94, 1.0). Trained readers have a high interobserver agreement for differentiating BE, squamous, and gastric cardia mucosa using OFDI. C1 [Sauk, Jenny; Kava, Lauren; Suter, Melissa; Gora, Michalina; Gallagher, Kevin; Rosenberg, Mireille; Woods, Kevin; Bouma, Brett E.; Tearney, Guillermo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sauk, Jenny; Ananthakrishnan, Ashwin; Nishioka, Norman; Woods, Kevin; Brugge, William; Forcione, David] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Coron, Emmanuel] Univ Hosp, Inst Digest Dis, Dept Gastroenterol & Hepatol, Nantes, France. [Lauwers, Gregory; Tearney, Guillermo] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Woods, Kevin] Emory Univ, Sch Med, Emory Clin Inc, Atlanta, GA 30322 USA. RP Tearney, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM jsauk@partners.org; emmanuel.coron@gmail.com; kava.lauren@gmail.com; msuter@partners.org; mgora@partners.org; kevinandrewgallagher@gmail.com; mrosenberg@partners.org; aananthakrishnan@partners.org; nnishioka@partners.org; glauwers@partners.org; Kevin.woods@emory.edu; wbrugge@partners.org; dforcione@partners.org; bbouma@helix.mgh.harvard.edu; gtearney@partners.org RI Coron, Emmanuel/K-2415-2015 FU National Institutes of Health [R01 CA103769] FX This work is supported by grants from the National Institutes of Health (R01 CA103769). NR 28 TC 16 Z9 16 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2013 VL 58 IS 8 BP 2261 EP 2265 DI 10.1007/s10620-013-2625-x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 194RR UT WOS:000322650900020 PM 23508980 ER PT J AU Pugh, MJV Marcum, ZA Copeland, LA Mortensen, EM Zeber, JE Noel, PH Berlowitz, DR Downs, JR Good, CB Alvarez, C Amuan, ME Hanlon, JT AF Pugh, Mary Jo V. Marcum, Zachary A. Copeland, Laurel A. Mortensen, Eric M. Zeber, John E. Noel, Polly H. Berlowitz, Dan R. Downs, John R. Good, Chester B. Alvarez, Carlos Amuan, Megan E. Hanlon, Joseph T. TI The Quality of Quality Measures: HEDISA (R) Quality Measures for Medication Management in the Elderly and Outcomes Associated with New Exposure SO DRUGS & AGING LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; ADVERSE DRUG EVENTS; OLDER-ADULTS; HEALTH OUTCOMES; BEERS CRITERIA; EXPLICIT CRITERIA; VETERANS; RISK; CARE; HOSPITALIZATIONS AB Clinical validation studies of the Healthcare Effectiveness Data and Information Set (HEDISA (R)) measures of inappropriate prescribing in the elderly are limited. The objective of this study was to examine associations of new exposure to high-risk medication in the elderly (HRME) and drug-disease interaction (Rx-DIS) with mortality, hospital admission, and emergency care. A retrospective database study was conducted examining new use of HRME and Rx-DIS in fiscal year 2006 (Oct 2005-Sep 2006; FY06), with index date being the date of first HRME/Rx-DIS exposure, or first day of FY07 if no HRME/Rx-DIS exposure. Outcomes were assessed 1 year after the index date. The participants were veterans who were a parts per thousand yen65 years old in FY06 and received Veterans Health Administration (VA) care in FY05-06. A history of falls/hip fracture, chronic renal failure, and/or dementia per diagnosis codes defined the Rx-DIS subsample. The variables included a number of new unique HRME drug exposures and new unique Rx-DIS drug exposure (0, 1, > 1) in FY06, and outcomes (i.e., 1-year mortality, hospital admission, and emergency care) up to 1 year after exposure. Descriptive statistics summarized variables for the overall HRME cohort and the Rx-DIS subset. Multivariable statistical analyses using generalized estimating equations (GEE) models with a logit link accounted for nesting of patients within facilities. For these latter analyses, we controlled for demographic characteristics, chronic disease states, and indicators of disease burden the previous year (e.g., number of prescriptions, emergency/hospital care). Among the 1,807,404 veterans who met inclusion criteria, 5.2 % had new HRME exposure. Of the 256,388 in the Rx-DIS cohort, 3.6 % had new Rx-DIS exposure. Multivariable analyses found that HRME was significantly associated with mortality [1: adjusted odds ratio (AOR) = 1.62, 95 % CI 1.56-1.68; > 1: AOR = 1.80, 95 % CI 1.45-2.23], hospital admission (1: AOR = 2.31, 95 % CI 2.22-2.40; > 1: AOR = 3.44, 95 % CI 3.06-3.87), and emergency care (1: AOR = 2.59, 95 % CI 2.49-2.70; > 1: AOR = 4.18, 95 % CI 3.71-4.71). Rx-DIS exposure was significantly associated with mortality (1: AOR = 1.60, 95 % CI 1.51-1.71; > 1: AOR = 2.00, 95 % CI 1.38-2.91), hospital admission for one exposure (1: AOR = 1.12, 95 % CI 1.03-1.27; > 1: AOR = 1.18, 95 % CI 0.71-1.95), and emergency care for two or more exposures (1: AOR = 1.06, 95 % CI 0.97-1.15; > 1: AOR = 2.0, 95 % CI 1.35-3.10). Analyses support the link between HRME/Rx-DIS exposure and clinically significant outcomes in older veterans. Now is the time to begin incorporating input from both patients who receive these medications and providers who prescribe to develop approaches to reduce exposure to these agents. C1 [Pugh, Mary Jo V.; Noel, Polly H.; Downs, John R.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.; Noel, Polly H.; Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Marcum, Zachary A.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Copeland, Laurel A.; Zeber, John E.] Cent Texas Vet Healthcare Syst, Temple, TX USA. [Copeland, Laurel A.; Zeber, John E.] Cent Texas Vet Hlth Care Syst, Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX USA. [Mortensen, Eric M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.; Alvarez, Carlos] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Berlowitz, Dan R.; Amuan, Megan E.] Edith Nourse Rogers Mem Vet Hosp, CHQOER, Bedford, MA USA. [Good, Chester B.] Vet Affairs Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Div Gen Med, Pittsburgh, PA USA. [Good, Chester B.] Pharm Benefits Management Serv, Dept Vet Affairs, Hines, IL USA. [Alvarez, Carlos] Texas Tech Univ, Hlth Sci Ctr, Dallas, TX USA. RP Pugh, MJV (reprint author), South Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Evidence Based Res Disseminat Implementat Ctr, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM PughM@uthscsa.edu FU VA Health Services Research and Development Service [IIR 06-062]; South Texas Veterans Healthcare System/Audie L. Murphy Division; VERDICT research program; Central Texas Veterans Healthcare System; Center for Applied Health Research FX This study was funded by VA Health Services Research and Development Service, IIR 06-062 (Dr. Pugh PI). The funding agency had no role in data collection, analysis, or manuscript development. No conflict of interest is reported for any co-authors. We also acknowledge assistance with manuscript preparation by Jeffrey Tabares, Margaret Wells, and Kathleen Franklin. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The authors acknowledge and appreciate support from the South Texas Veterans Healthcare System/Audie L. Murphy Division and the VERDICT research program, and from the Central Texas Veterans Healthcare System, Center for Applied Health Research. Data from this paper was presented at the VA Health Services Research and Development Annual Research Meeting, National Harbor, MD, July 2012. NR 49 TC 9 Z9 9 U1 0 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X EI 1179-1969 J9 DRUG AGING JI Drugs Aging PD AUG PY 2013 VL 30 IS 8 BP 645 EP 654 DI 10.1007/s40266-013-0086-8 PG 10 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 186AW UT WOS:000322014600007 PM 23645530 ER PT J AU Addington, J Stowkowy, J Cadenhead, KS Cornblatt, BA McGlashan, TH Perkins, DO Seidman, LJ Tsuang, MT Walker, EF Woods, SW Cannon, TD AF Addington, Jean Stowkowy, Jacqueline Cadenhead, Kristin S. Cornblatt, Barbara A. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Cannon, Tyrone D. TI Early traumatic experiences in those at clinical high risk for psychosis SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Article DE clinical high risk; prodrome; psychosis; risk; trauma ID CORE SCHEMA SCALES; ULTRA-HIGH-RISK; CHILDHOOD TRAUMA; SYMPTOMS; SCHIZOPHRENIA; ASSOCIATIONS; POPULATION; PARANOIA AB Aim: Several lines of evidence suggest a possible association between a history of trauma in childhood and later psychosis or psychotic-like experiences. The purpose of this study was to determine the extent of childhood trauma and bullying in young people at clinical high risk (CHR) of developing psychosis. Methods: The sample consisted of 360 individuals who were at CHR of developing psychosis and 180 age- and gender-matched healthy controls. All participants were assessed on past trauma and bullying. The CHR participants were also assessed on a range of psychopathology and functioning. Results: Individuals at CHR reported significantly more trauma and bullying than healthy controls. Those who had experienced past trauma and bullying were more likely to have increased levels of depression and anxiety and a poorer sense of self. Conclusions: These results offer preliminary support for an association between a history of trauma and later subthreshold symptoms. C1 [Addington, Jean; Stowkowy, Jacqueline] Univ Calgary, Dept Psychiat, Calgary, AB T2N 4Z6, Canada. [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [McGlashan, Thomas H.; Woods, Scott W.; Cannon, Tyrone D.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA USA. RP Addington, J (reprint author), Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada. EM jmadding@ucalgary.ca FU National Institute of Mental Health [U01MH081984, U01 MH081928, P50 MH080272, SCDMH82 101008006, R01 MH60720, U01 MH082022, K24 MH76191, MH081902, U01MH081988, U01MH082022, UO1 MH081857-05] FX This study was supported by the National Institute of Mental Health (grant U01MH081984 to Dr Addington; grants U01 MH081928, P50 MH080272, Commonwealth of Massachusetts SCDMH82 101008006 to Dr Seidman; grants R01 MH60720, U01 MH082022 and K24 MH76191 to Dr Cadenhead; grant to Dr Cannon; grant MH081902 to Dr Cannon; grant U01MH081988 to Dr Walker; grant U01MH082022 to Dr Woods; and) grant UO1 MH081857-05 to Dr Cornblatt. The NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 28 TC 28 Z9 30 U1 3 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD AUG PY 2013 VL 7 IS 3 BP 300 EP 305 DI 10.1111/eip.12020 PG 6 WC Psychiatry SC Psychiatry GA 188BS UT WOS:000322167200011 PM 23343384 ER PT J AU Abbaszadegan, MR Hassani, S Vakili, R Saberi, MR Baradaran-Heravi, A A'rabi, A Hashemipour, M Razzaghi-Azar, M Moaven, O Baratian, A Ahadian, M Keify, F Meurice, N AF Abbaszadegan, Mohammad Reza Hassani, Soolmaz Vakili, Rahim Saberi, Mohammad Reza Baradaran-Heravi, Alireza A'rabi, Azadeh Hashemipour, Mahin Razzaghi-Azar, Maryam Moaven, Omeed Baratian, Ali Ahadian, Mitra Keify, Fatemeh Meurice, Nathalie TI Two novel mutations in CYP11B1 and modeling the consequent alterations of the translated protein in classic congenital adrenal hyperplasia patients SO ENDOCRINE LA English DT Article DE Congenital adrenal hyperplasia; CYP11B1; Mutation; Protein modeling; Prenatal diagnosis ID STEROID 11-BETA-HYDROXYLASE DEFICIENCY; BETA-HYDROXYLASE DEFICIENCY; LEYDIG-CELL TUMOR; 11-HYDROXYLASE DEFICIENCY; PRENATAL-DIAGNOSIS; 21-HYDROXYLASE DEFICIENCY; NORTHEASTERN IRAN; POINT MUTATIONS; GENE; HYPERTENSION AB Mutations in the 11 beta-hydroxylase (CYP11B1) gene are the second leading cause of congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by adrenal insufficiency, virilization of female external genitalia, and hypertension with or without hypokalemic alkalosis. Molecular analysis of CYP11B1 gene in CAH patients with 11 beta-hydroxylase deficiency was performed in this study. Cycle sequencing of 9 exons in CYP11B1 was performed in 5 unrelated families with 11 beta-hydroxylase deficient children. Three-dimensional models for the normal and mutant proteins and their affinity to their known substrates were examined. Analysis of the CYP11B1 gene revealed two novel mutations, a small insertion in exon 7 (InsAG393) and a small deletion in exon 2 (DelG766), and three previously known missense mutations (T318M, Q356X, and R427H). According to docking results, the affinity of the protein to its substrates is highly reduced by these novel mutations. DelG766 has more negative impact on the protein in comparison to InsAG393. The novel mutations, InsAG393 and DelG766, change the folding of the protein and disrupt the enzyme's active site as it was measured in the protein modeling and substrate binding analysis. Molecular modeling and sequence conservation were predictive of clinical severity of the disease and correlated with the clinical diagnosis of the patients. C1 [Abbaszadegan, Mohammad Reza; Hassani, Soolmaz; A'rabi, Azadeh] Mashhad Univ Med Sci, Avicenna Res Inst, Immunol Res Ctr, Div Human Genet, Mashhad 9196773117, Iran. [Abbaszadegan, Mohammad Reza; Ahadian, Mitra; Keify, Fatemeh] Pardis Clin & Genet Lab, Mashhad, Iran. [Abbaszadegan, Mohammad Reza; Meurice, Nathalie] Translat Genom Res Inst, Phoenix, AZ USA. [Hassani, Soolmaz; Vakili, Rahim] Mashhad Univ Med Sci, Imam Reza Hosp, Dept Pediat, Mashhad 9196773117, Iran. [Saberi, Mohammad Reza; Baratian, Ali] Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad 9196773117, Iran. [Baradaran-Heravi, Alireza] Univ British Columbia, Dept Med Genet, Child & Family Res Inst, Vancouver, BC, Canada. [Hashemipour, Mahin] Esfahan Univ Med Sci, Esfahan Endocrine & Metab Res Ctr, Esfahan, Iran. [Razzaghi-Azar, Maryam] Iran Univ Med Sci, Ali Asghar Hosp, Dept Pediat, Tehran, Iran. [Moaven, Omeed] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Abbaszadegan, MR (reprint author), Mashhad Univ Med Sci, Avicenna Res Inst, Immunol Res Ctr, Div Human Genet, Mashhad 9196773117, Iran. EM abbaszadeganmr@mums.ac.ir OI Moaven, Omeed/0000-0002-0560-0457 FU Mashhad University of Medical Sciences [86426] FX This study was supported by a Grant from Mashhad University of Medical Sciences (#86426). NR 36 TC 8 Z9 9 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X J9 ENDOCRINE JI Endocrine PD AUG PY 2013 VL 44 IS 1 BP 212 EP 219 DI 10.1007/s12020-012-9861-2 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192KP UT WOS:000322483500032 PM 23345044 ER PT J AU Abbaszadegan, MR Hassani, S Vakili, R Saberi, MR Baradaran-Heravi, A A'rabi, A Hashemipour, M Razzaghi-Azar, M Moaven, O Baratian, A Ahadian, M Keify, F Meurice, N AF Abbaszadegan, Mohammad Reza Hassani, Soolmaz Vakili, Rahim Saberi, Mohammad Reza Baradaran-Heravi, Alireza A'rabi, Azadeh Hashemipour, Mahin Razzaghi-Azar, Maryam Moaven, Omeed Baratian, Ali Ahadian, Mitra Keify, Fatemeh Meurice, Nathalie TI Two novel mutations in CYP11B1 and modeling the consequent alterations of the translated protein in classic congenital adrenal hyperplasia patients (vol 44, pg 212, 2013) SO ENDOCRINE LA English DT Correction C1 [Abbaszadegan, Mohammad Reza; Hassani, Soolmaz; A'rabi, Azadeh] Mashhad Univ Med Sci, Avicenna Res Inst, Immunol Res Ctr, Div Human Genet, Mashhad 9196773117, Iran. [Abbaszadegan, Mohammad Reza; Ahadian, Mitra; Keify, Fatemeh] Pardis Clin & Genet Lab, Mashhad, Iran. [Abbaszadegan, Mohammad Reza; Meurice, Nathalie] Translat Genom Res Inst, Phoenix, AZ USA. [Hassani, Soolmaz; Vakili, Rahim] Mashhad Univ Med Sci, Imam Reza Hosp, Dept Pediat, Mashhad 9196773117, Iran. [Saberi, Mohammad Reza; Baratian, Ali] Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad 9196773117, Iran. [Baradaran-Heravi, Alireza] Univ British Columbia, Dept Med Genet, Child & Family Res Inst, Vancouver, BC, Canada. [Hashemipour, Mahin] Esfahan Univ Med Sci, Esfahan Endocrine & Metab Res Ctr, Esfahan, Iran. [Razzaghi-Azar, Maryam] Univ Tehran Med Sci, Inborn Error Metab Res Ctr EMRI, Tehran, Iran. [Moaven, Omeed] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Abbaszadegan, MR (reprint author), Mashhad Univ Med Sci, Avicenna Res Inst, Immunol Res Ctr, Div Human Genet, Mashhad 9196773117, Iran. EM abbaszadeganmr@mums.ac.ir NR 1 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X J9 ENDOCRINE JI Endocrine PD AUG PY 2013 VL 44 IS 1 BP 271 EP 271 DI 10.1007/s12020-013-9957-3 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192KP UT WOS:000322483500042 ER PT J AU Li, JJ Shan, HB Gu, MF He, L He, LJ Chen, LM Luo, GY Xu, GL AF Li, J. -J. Shan, H. -B. Gu, M. -F. He, L. He, L. -J. Chen, L. -M. Luo, G. -Y. Xu, G. -L. TI Endoscopic ultrasound combined with submucosal saline injection for differentiation of T1a and T1b esophageal squamous cell carcinoma: a novel technique SO ENDOSCOPY LA English DT Article ID CANCER; ACCURACY; EUS AB Endoscopic ultrasound (EUS) is the optimum method for investigation of early esophageal squamous cell carcinoma (ESCC). However, it is difficult to substage early ESCC as T1a or T1b. The aim of this study was to improve the staging accuracy of early ESCC by using EUS combined with submucosal saline injection (SSI). The study enrolled 15 patients with suspected early ESCC who were examined by EUS and subsequently by SSI combined with EUS. The patients then underwent endoscopic or surgical resection within 10 days. The accuracy of EUS staging (alone or following SSI) was evaluated and compared with the pathological results postoperatively. No severe complications of the SSI arose. EUS plus SSI easily distinguished the mucosa from the lesion and the submucosa because of the low-echoic saline-filled cushion in the submucosa. The accuracy of SSI combined with EUS for staging T1a or T1b was 86.7%, which was better than that using EUS alone (60.0%). C1 [Li, J. -J.; Shan, H. -B.; He, L. -J.; Chen, L. -M.; Luo, G. -Y.; Xu, G. -L.] Sun Yat Sen Univ, Dept Endoscopy, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China. [Gu, M. -F.] Sun Yat Sen Univ, State Key Lab Oncol South China, Dept Radiat Oncol, Guangzhou 510060, Guangdong, Peoples R China. [He, L.; Luo, G. -Y.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [He, L.; Luo, G. -Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Li, JJ (reprint author), Sun Yat Sen Univ, Dept Endoscopy, State Key Lab Oncol South China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China. EM lijj@sysucc.org.cn FU Science and Technology Plan Projects of Guangdong Province, P.R. China [2011B080701015] FX This study was funded by Science and Technology Plan Projects of Guangdong Province, P.R. China (Grant NO: 2011B080701015). NR 9 TC 7 Z9 8 U1 1 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD AUG PY 2013 VL 45 IS 8 BP 667 EP 670 DI 10.1055/s-0033-1344024 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 187IY UT WOS:000322112100010 PM 23807801 ER PT J AU French, JA White, HS Klitgaard, H Holmes, GL Privitera, MD Cole, AJ Quay, E Wiebe, S Schmidt, D Porter, RJ Arzimanoglou, A Trinka, E Perucca, E AF French, Jacqueline A. White, H. Steve Klitgaard, Henrik Holmes, Gregory L. Privitera, Michael D. Cole, Andrew J. Quay, Ellinor Wiebe, Samuel Schmidt, Dieter Porter, Roger J. Arzimanoglou, Alexis Trinka, Eugen Perucca, Emilio TI Development of new treatment approaches for epilepsy: Unmet needs and opportunities SO EPILEPSIA LA English DT Article DE Antiseizure therapy; Epilepsy syndromes; Antiepileptogenic therapy; Animal models ID TEMPORAL-LOBE EPILEPSY; FEBRILE CONVULSIONS; ANTIEPILEPTIC DRUGS; NATIONAL COHORT; SEIZURES; CHILDHOOD; HISTORY; INJURY; AGE AB A working group was created to address clinical "gaps to care" as well as opportunities for development of new treatment approaches for epilepsy. The working group primarily comprised clinicians, trialists, and pharmacologists. The group identified a need for better animal models for both efficacy and tolerability, and noted that animal models for potential disease-modifying or antiepileptogenic effect should mirror conditions in human trials. For antiseizure drugs (ASDs), current animal models have not been validated with respect to their relationship to efficacy in common epilepsy syndromes. The group performed an "expert opinion" survey of perceived efficacy of the available ASDs, and identified a specific unmet need for ASDs to treat tonic-atonic and myoclonic seizures. No correlation has as yet been demonstrated between animal models of tolerability and adverse effects (AEs), versus tolerability in humans. There is a clear opportunity for improved therapies in relation to dose-related AEs. The group identified common and rare epilepsy syndromes that could represent opportunities for clinical trials. They identified opportunities for antiepileptogenic (AEG) therapies in both adults and children, acknowledging that the presence of a biomarker would substantially improve the chances of a successful trial. However, the group acknowledged that disease-modifying therapies (given after the first seizure or after the development of epilepsy) would be easier to study than AEG therapies. C1 [French, Jacqueline A.] NYU, Sch Med, Dept Neurol, New York, NY 10016 USA. [White, H. Steve] Univ Utah, Dept Pharmacol & Toxicol, Anticonvulsant Drug Dev Program, Salt Lake City, UT 84112 USA. [Klitgaard, Henrik] UCB Pharma, Neurosci Therapeut Area, Brussels, Belgium. [Holmes, Gregory L.] Geisel Sch Med Dartmouth, Dept Neurol, Hanover, NH USA. [Holmes, Gregory L.] Geisel Sch Med Dartmouth, Dept Pediat, Hanover, NH USA. [Privitera, Michael D.] Univ Cincinnati, Inst Neurosci, Cincinnati, OH USA. [Cole, Andrew J.] Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. [Cole, Andrew J.] Harvard Univ, Sch Med, Boston, MA USA. [Quay, Ellinor] NYU, Sch Med, New York, NY USA. [Wiebe, Samuel] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Wiebe, Samuel] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. [Wiebe, Samuel] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Schmidt, Dieter] Epilepsy Res Grp, Berlin, Germany. [Porter, Roger J.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Porter, Roger J.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Arzimanoglou, Alexis] Univ Hosp Lyon HCL, Epilepsy Sleep & Pediat Neurophysiol Dept, Lyon, France. [Arzimanoglou, Alexis] Lyon Neurosci Res Ctr CRNL, Lyon, France. [Trinka, Eugen] Paracelsus Med Univ Salzburg, Dept Neurol, Christian Doppler Klin, Salzburg, Austria. [Perucca, Emilio] Univ Pavia, Dept Internal Med & Therapeut, I-27100 Pavia, Italy. [Perucca, Emilio] Natl Inst Neurol IRCCS C Mondino Fdn, Pavia, Italy. RP French, JA (reprint author), NYU, Sch Med, Dept Neurol, Comprehens Epilepsy Ctr, 223 E 34th St, New York, NY 10016 USA. EM Jacqueline.french@nyumc.org RI Cognitive Neuroscience, Centre for/C-7888-2011; OI French, Jacqueline/0000-0003-2242-8027 FU Epilepsy Study Consortium; Cyberonics; Eisai Medical Research; EntraPharmaceuticals; GlaxoSmithKline; Icagen, Inc.; Johnson Johnson; Marinus; Neuro-therapeutics; NeuroVista Corporation; Ono Pharma U.S.A., Inc.; Lundbeck; Pfizer; Sepracor; Sunovion; SK Life Science; Supernus Pharmaceuticals; UCB Inc/Schwarz Pharma; Upsher Smith; Valeant; Vertex; NINDS; Milken Foundation; Epilepsy Therapy Project; University of Calgary; Canadian Institutes of Health Research; European Union; Italian Medicines Agency; Italian Ministry of Health; Italian Ministry for Education, University and Research; Bial; Eisai; Medichem; Sun Pharma; Supernus; UCB Pharma; Upsher-Smith; Biogen-Idec; Medtronics; UCB; Sanofi-Aventis; FWF-Fond zur Wissenschaftsforderung, Osterreich, Jubilaumsfond der Osterreichischen Nationalbank und Red Bull; National Institute of Neurological Disorders and Stroke (NINDS); Insero Health; Janssen Pharmaceuticals, Inc.; Upsher-Smith Laboratories; Citizen's United for Research in Epilepsy; U.S. Food and Drug Administration; American Epilepsy Society; Epilepsy Foundation; Neuren; Viropharma; European Community; Novartis Pharma FX Jacqueline French serves as the president of The Epilepsy Study Consortium, a nonprofit organization. New York University, where Dr. French is employed, receives a fixed amount from the Epilepsy Study Consortium toward Dr French's salary. The money is for work performed by Dr. French on behalf of The Epilepsy Study Consortium, for consulting and clinical trial-related activities. Dr French receives no personal income for these activities. Within the last year, The Epilepsy Study Consortium received payments from the following: Cyberonics, Eisai Medical Research, EntraPharmaceuticals, GlaxoSmithKline, Icagen, Inc., Johnson & Johnson, Marinus, Neuro-therapeutics, NeuroVista Corporation, Ono Pharma U.S.A., Inc., Lundbeck, Pfizer, Sepracor, Sunovion, SK Life Science, Supernus Pharmaceuticals, UCB Inc/Schwarz Pharma, Upsher Smith, Valeant, and Vertex. Dr. French also received funding from NINDS, Milken Foundation, and the Epilepsy Therapy Project.; Samuel Wiebe holds the Hopewell professorship of clinical neurosciences research, funded by the University of Calgary, and receives research funding from Canadian Institutes of Health Research.; Emilio Perucca received research grants from the European Union, the Italian Medicines Agency, the Italian Ministry of Health, and the Italian Ministry for Education, University and Research. He also received speaker's or consultancy fees and/or research grants from Bial, Eisai, GlaxoSmithKline, Medichem, Pfizer, Sun Pharma, Supernus, UCB Pharma, Upsher-Smith, and Vertex.; Eugen Trinka has acted as a paid consultant to Eisai, Biogen-Idec, Medtronics, Bial, and UCB. He has received research funding from UCB, Biogen-Idec, Sanofi-Aventis, and speakers' honoraria from Bial, Cyberonics, Desitin Pharma, Eisai, Gerot, Bohringer, Sanofi, Medis, and UCB. He has received research grants from FWF-Fond zur Wissenschaftsforderung, Osterreich, Jubilaumsfond der Osterreichischen Nationalbank und Red Bull.; H. Steve White has received research grants and a contract from the National Institute of Neurological Disorders and Stroke (NINDS). He has also received speaker's or consultancy fees from Insero Health, Janssen Pharmaceuticals, Inc., Upsher-Smith Laboratories, UCB Pharma, and Citizen's United for Research in Epilepsy. Dr. White is also one of two scientific co-founders of NeuroAdjuvants, Inc., Salt Lake City, UT.; Michael Privitera has received grant funding from the U.S. Food and Drug Administration, the American Epilepsy Society, the Epilepsy Foundation, Eisai, UCB, and Neuren and has been a Consultant (DSMB) for Upsher-Smith and Lilly.; Alexis Arzimanoglou has received speaker's or consultancy fees from Cyberonics, Eisai, GlaxoSmithKline, UCB Pharma, and Viropharma.; He also sits on a safety monitoring board for UCB and received educational and European Community grants for which remuneration was made to University Hospital of Lyons or to a research association of his department.; Dieter Schmidt has received hospitality and speaker fees from Eisai, GSK, Novartis Pharma, Sun Pharma, and ViroPharma, in the past three years. NR 32 TC 16 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2013 VL 54 SU 4 SI SI BP 3 EP 12 DI 10.1111/epi.12294 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 193TR UT WOS:000322584900002 PM 23909849 ER PT J AU Galanopoulou, AS Kokaia, M Loeb, JA Nehlig, A Pitkanen, A Rogawski, MA Staley, KJ Whittemore, VH Dudek, FE AF Galanopoulou, Aristea S. Kokaia, Merab Loeb, Jeffrey A. Nehlig, Astrid Pitkanen, Asla Rogawski, Michael A. Staley, Kevin J. Whittemore, Vicky H. Dudek, F. Edward TI Epilepsy therapy development: Technical and methodologic issues in studies with animal models SO EPILEPSIA LA English DT Article DE Pharmacokinetics; Video-electroencephalography; Regulatory requirements; Nonpharmacological treatment; Infrastructure ID SEIZURES; PUBLICATION; INJURY; DRUGS; RATS; ILAE AB The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting practices that will enhance the uniformity, reliability, and reporting of early stage preclinical studies with animal seizure and epilepsy models that aim to develop and evaluate new therapies for seizures or epilepsies, using multidisciplinary approaches. The topics considered include the following: (1) implementation of better study design and reporting practices; (2) incorporation in the study design and analysis of covariants that may influence outcomes (including species, age, sex); (3) utilization of approaches to document target relevance, exposure, and engagement by the tested treatment; (4) utilization of clinically relevant treatment protocols; (5) optimization of the use of video-electroencephalography (EEG) recordings to best meet the study goals; and (6) inclusion of outcome measures that address the tolerability of the treatment or study end points apart from seizures. We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers. C1 [Galanopoulou, Aristea S.] Albert Einstein Coll Med, Lab Dev Epilepsy, Saul R Korey Dept Neurol, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA. [Kokaia, Merab] Univ Lund Hosp, Expt Epilepsy Grp, Div Neurol, Wallenberg Neurosci Ctr, S-22185 Lund, Sweden. [Loeb, Jeffrey A.] Wayne State Univ, Dept Neurol, Detroit, MI USA. [Loeb, Jeffrey A.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Nehlig, Astrid] Hop Necker Enfants Malad, INSERM, U663, Paris, France. [Pitkanen, Asla] Univ Eastern Finland, Dept Neurobiol, AI Virtanen Inst Mol Sci, Kuopio, Finland. [Pitkanen, Asla] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland. [Rogawski, Michael A.] Univ Calif Davis, Dept Neurol, Sch Med, Sacramento, CA 95817 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. [Whittemore, Vicky H.] NINDS, NIH, Bethesda, MD 20892 USA. [Dudek, F. Edward] Univ Utah, Sch Med, Dept Neurosurg, Salt Lake City, UT USA. RP Galanopoulou, AS (reprint author), Albert Einstein Coll Med, 1410 Pelham Pkwy South,Kennedy Ctr Rm 306, Bronx, NY 10461 USA. EM aristea.galanopoulou@einstein.yu.edu RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU AES; ILAE; CURE; Epilepsy Therapy Project; Autism Speaks FX We would like to acknowledge the invaluable advice during our proceedings by H. Steve White (University of Utah, Salt lake City, Utah), James Cloyd (Center for Orphan Drug Research, University of Minnesota, Minneapolis, Minnesota, U. S. A.), and Elisabetta Vaudano (Innovative Medicines Initiative, Brussels, Belgium). We would also like to thank the AES, ILAE, CURE, Epilepsy Therapy Project, and Autism Speaks for their financial support of the AES/ILAE Joint workshop in London (September 2012). NR 38 TC 19 Z9 19 U1 0 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2013 VL 54 SU 4 SI SI BP 13 EP 23 DI 10.1111/epi.12295 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 193TR UT WOS:000322584900003 PM 23909850 ER PT J AU Engel, J Pitkanen, A Loeb, JA Dudek, FE Bertram, EH Cole, AJ Moshe, SL Wiebe, S Jensen, FE Mody, I Nehlig, A Vezzani, A AF Engel, Jerome, Jr. Pitkanen, Asla Loeb, Jeffrey A. Dudek, F. Edward Bertram, Edward H., III Cole, Andrew J. Moshe, Solomon L. Wiebe, Samuel Jensen, Frances E. Mody, Istvan Nehlig, Astrid Vezzani, Annamaria TI Epilepsy biomarkers SO EPILEPSIA LA English DT Article DE Biomarkers; Surrogate markers; Epileptogenesis; Ictogenesis ID HIGH-FREQUENCY OSCILLATIONS; ELECTROPHYSIOLOGICAL BIOMARKERS; ORGANIZATION AB A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds. C1 [Engel, Jerome, Jr.; Mody, Istvan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Pitkanen, Asla] Univ Eastern Finland, Dept Neurobiol, AI Virtanen Inst Mol Sci, Kuopio, Finland. [Loeb, Jeffrey A.] Univ Illinois, Dept Neurol & Rehabil, Chicago, IL USA. [Dudek, F. Edward] Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA. [Bertram, Edward H., III] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Moshe, Solomon L.] Albert Einstein Coll Med, Saul R Korey Dept Neurol, Dominick P Purpura Dept Neurosci, Dept Pediat,Lab Dev Epilepsy,Montefiore Einstein, Bronx, NY 10467 USA. [Moshe, Solomon L.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Wiebe, Samuel] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Jensen, Frances E.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Nehlig, Astrid] Hop Necker Enfants Malad, INSERM, U663, Paris, France. [Vezzani, Annamaria] Mario Negri Inst Pharmacol Res, Dept Neurosci, Milan, Italy. RP Engel, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM engel@ucla.edu FU NIH; Epilepsy Therapy Project; Resnick Foundation; Oppenheimer Foundation; Milken Family Foundation; Department of Defense; UCLA Coelho Chair; INSERM; Academy of Finland; Sigrid Juselius Foundation; Citizens United for Research in Epilepsy (CURE); Fondazione Cariplo; Progretto Ministero della Salute; University of Calgary Hopewell Chair FX Original work cited by the authors was supported by grants from NIH, Epilepsy Therapy Project, Resnick Foundation, Oppenheimer Foundation, Milken Family Foundation, Department of Defense, UCLA Coelho Chair, INSERM, Academy of Finland, The Sigrid Juselius Foundation, Citizens United for Research in Epilepsy (CURE), Fondazione Cariplo, Progretto Ministero della Salute and the University of Calgary Hopewell Chair. NR 12 TC 47 Z9 49 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2013 VL 54 SU 4 SI SI BP 61 EP 69 DI 10.1111/epi.12299 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 193TR UT WOS:000322584900007 PM 23909854 ER PT J AU O'Brien, TJ Ben-Menachem, E Bertram, EH Collins, SD Kokaia, M Lerche, H Klitgaard, H Staley, KJ Vaudano, E Walker, MC Simonato, M AF O'Brien, Terence J. Ben-Menachem, Elinor Bertram, Edward H., III Collins, Stephen D. Kokaia, Merab Lerche, Holger Klitgaard, Henrik Staley, Kevin J. Vaudano, Elisabetta Walker, Matthew C. Simonato, Michele TI Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development SO EPILEPSIA LA English DT Article DE Preclinical development; Antiepilepsy therapies; Multicenter AB There is a pressing need to address the current major gaps in epilepsy treatment, in particular drug-resistant epilepsy, antiepileptogenic therapies, and comorbidities. A major concern in the development of new therapies is that current preclinical testing is not sufficiently predictive for clinical efficacy. Methodologic limitations of current preclinical paradigms may partly account for this discrepancy. Here we propose and discuss a strategy for implementing a "phase II" multicenter preclinical drug trial model based on clinical phase II/III studies designed to generate more rigorous preclinical data for efficacy. The goal is to improve the evidence resulting from preclinical studies for investigational new drugs that have shown strong promise in initial preclinical "phase I" studies. This should reduce the risk for expensive clinical studies in epilepsy and therefore increase the appeal for funders (industry and government) to invest in their clinical development. C1 [O'Brien, Terence J.] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Parkville, Vic 3052, Australia. [O'Brien, Terence J.] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3052, Australia. [Ben-Menachem, Elinor] Sahlgrens Acad, Inst Clin Neurosci, Gothenburg, Sweden. [Bertram, Edward H., III] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. [Collins, Stephen D.] NeuroTherapeut Pharma, Chicago, IL USA. [Kokaia, Merab] Univ Lund Hosp, Expt Epilepsy Grp, Wallenberg Neurosci Ctr, BMC, S-22185 Lund, Sweden. [Lerche, Holger] Univ Tubingen Hosp, Dept Neurol & Epileptol, Hertie Inst Clin Brain Res, Tubingen, Germany. [Klitgaard, Henrik] UCB Pharma, Braine Lalleud, Belgium. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. [Vaudano, Elisabetta] IMI, Brussels, Belgium. [Walker, Matthew C.] UCL Inst Neurol, London, England. [Simonato, Michele] Univ Ferrara, Dept Med Sci, Pharmacol Sect, I-44100 Ferrara, Italy. [Simonato, Michele] Natl Inst Neurosci, Ferrara, Italy. RP O'Brien, TJ (reprint author), Royal Melbourne Hosp, Dept Med, Parkville, Vic 3050, Australia. EM obrientj@unimelb.edu.au; michele.simonato@unife.it RI O'Brien, Terence/L-8102-2013; Walker, Matthew/C-1577-2008; OI Walker, Matthew/0000-0002-0812-0352; O'Brien, Terence/0000-0002-7198-8621 FU NHMRC (Australia); Royal Melbourne Hospital Neuroscience Foundation; Sanofi-Aventis; UCB; SciGen; GlaxoSmithKline; Novartis; Janssen-Cilag; German Federal Ministry of Education and Research (BMBF); German Research Foundation (DFG); European Commission; European Union (Epixchange); Italian Ministry for Research and the University; Chiesi Pharmaceuticals (Italy); Sanofi-Synthelabo; Medical Research Council (UK); Wellcome Trust; NC3Rs; Epilepsy Research UK; National Institute of Health Research (UK); UCLH; UCL biomedical research centre; Bial; Eisai Inc.; V(sic)astra G(sic)otaland Region FX Terence J. O'Brien has received research grant support from the NHMRC (Australia), the Royal Melbourne Hospital Neuroscience Foundation, Sanofi-Aventis, UCB, SciGen, GlaxoSmithKline, Novartis, and Janssen-Cilag; and speaker honorarium from Sanofi-Aventis, UCB, SciGen, GlaxoSmithKline, and Janssen-Cilag. Henrik Klitgaard is an employee at UCB Pharma. HL has received funding from the German Federal Ministry of Education and Research (BMBF), German Research Foundation (DFG), European Commission, UCB, Sanofi-Aventis, travel support or honoraria for speaker's engagement and consulting from Cyberonics, Desitin, Eisai, GlaxoSmithKline, Medtronic, Pfizer, UCB, and Valeant. Michele Simonato has received research funding from the European Union (Epixchange), the Italian Ministry for Research and the University (Prin 2010-11), GlaxoSmithKline, Chiesi Pharmaceuticals (Italy), Sanofi-Synthelabo, and Schering-Plough. Matthew C. Walker, has received research funding support from Medical Research Council (UK), Wellcome Trust, NC3Rs, Epilepsy Research UK, National Institute of Health Research (UK), UCLH and UCL biomedical research centre and European Union and speaker honorarium from UCB, GlaxoSmithKline, Viropharma and Eisai. Elinor Ben-Menachem has been a Consultant for Eisai, BIal, Lundbeck, Electrocore, Janssen Cilag, and Biocontrol. She receives research support from UCB, Bial, and Eisai Inc. and V(sic)astra G(sic)otaland Region. She is Chief Editor of Acta Neurologica Scandinavica. Edward H. Bertram III has received research funding from the National Institutes of Health. NR 6 TC 5 Z9 5 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2013 VL 54 SU 4 SI SI BP 70 EP 74 DI 10.1111/epi.12300 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 193TR UT WOS:000322584900008 PM 23909855 ER PT J AU Lubitz, SA Husser, D AF Lubitz, Steven A. Husser, Daniela TI Genomic risk scores in atrial fibrillation: predicting the unpredictable? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID COMMUNITY; COHORT C1 [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Husser, Daniela] Heart Ctr Leipzig, Dept Electrophys, D-04289 Leipzig, Germany. RP Husser, D (reprint author), Heart Ctr Leipzig, Dept Electrophys, Strumpellstr 39, D-04289 Leipzig, Germany. EM dani11@gmx.net NR 15 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2013 VL 34 IS 29 SI SI BP 2227 EP 2229 DI 10.1093/eurheartj/eht106 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 194QZ UT WOS:000322649100006 PM 23585492 ER PT J AU Kandala, J Upadhyay, GA Altman, RK Parks, KA Orencole, M Mela, T Heist, EK Singh, JP AF Kandala, Jagdesh Upadhyay, Gaurav A. Altman, Robert K. Parks, Kimberly A. Orencole, Mary Mela, Theofanie Heist, E. Kevin Singh, Jagmeet P. TI QRS morphology, left ventricular lead location, and clinical outcome in patients receiving cardiac resynchronization therapy SO EUROPEAN HEART JOURNAL LA English DT Article DE Cardiac resynchronization therapy; Left ventricular lead location; Electrical delay; QRS morphology ID BUNDLE-BRANCH BLOCK; RANDOMIZED-CONTROLLED-TRIALS; CHRONIC HEART-FAILURE; EVENT REDUCTION; ACTIVATION; IMPACT; DEFIBRILLATOR; DYSFUNCTION; PREDICTORS; DELAY AB Several studies have reported a poor outcome with cardiac resynchronization therapy (CRT) in non-left bundle branch block (LBBB) patients. Although the left ventricular (LV) lead location is an important determinant of the clinical outcome, there is scant information regarding its role in non-LBBB patients. This study sought to examine the impact of electrical and anatomical location of the LV lead in relation to baseline QRS morphology on the CRT outcome. A left ventricular lead electrical delay (LVLED) was measured intra-procedurally as an interval between QRS onset on the surface electrocardiogram (ECG) to the peak of sensed electrogram on LV lead and corrected for QRS width. The impact of the LVLED on time to first heart failure hospitalization (HFH), and composite outcome of all-cause mortality, HFH, LVAD implantation, and cardiac transplantation at 3 years was assessed. Among 144 patients (age 67 12 years, QRS duration 156 28 ms, non-LBBB 43), HFH was higher in non-LBBB compared with LBBB (43.5 vs. 24, P 0.015). Within LBBB, patients with the long LVLED (50) had 17 HFH vs. 53 in the short LVLED (50), P 0.002. Likewise in non-LBBB, patients with the long LVLED compared with the short LVLED had a lower HFH (36 vs. 61, P 0.026). In adjusted Cox proportional hazards model, the long LVLED in LBBB and non-LBBB was associated with an improved outcome. Specifically, in non-LBBB, LVLED 50 was associated with improved event-free survival with respect to time to first HFH (HR: 0.34; P 0.011) and composite outcome (HR: 0.41; P 0.019). Cardiac resynchronization therapy delivered from an LV pacing site characterized by the long LVLED was associated with the favourable outcome in LBBB and non-LBBB patients. C1 [Kandala, Jagdesh; Upadhyay, Gaurav A.; Altman, Robert K.; Orencole, Mary; Heist, E. Kevin; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Cardiac Arrhythmia Serv,Cardiol Div, Boston, MA 02114 USA. [Parks, Kimberly A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Heart Failure Serv,Cardiol Div, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Cardiac Arrhythmia Serv,Cardiol Div, Boston, MA 02114 USA. EM jsingh@partners.org OI Altman, Robert/0000-0002-1612-3561 FU Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology of the Heart Rhythm Society; Biotronik; Boston Scientific Corp.; Sorin; St Jude Medical; Medtronic, Inc. FX J.K., R. K. A., and M.O. report no significant financial disclosures. G. A. U. received salary support from the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology of the Heart Rhythm Society. E. K. H. reports Biotronik (honoraria/research grants), Boston Scientific Corp. (consultant/honoraria/research grants), Sorin (consultant/honoraria/research grants), and St Jude Medical (consultant/honoraria/research grants). T. M. reports Boston Scientific Corp. (honoraria), Medtronic, Inc. (honoraria), and St Jude Medical (honoraria). J.P.S. reports St Jude Medical (consultant/honoraria/research grants), Medtronic, Inc. (consultant/honoraria/research grants), Boston Scientific Corp. (consultant/honoraria/research grants), Biotronik (consultant/honoraria/research grants), Sorin Group (consultant/honoraria), CardioInsight, Inc. (consultant), and Respicardia, Inc. (consultant). K. A. P. Thoratec (consultant). NR 23 TC 28 Z9 29 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2013 VL 34 IS 29 SI SI BP 2252 EP 2262 DI 10.1093/eurheartj/eht123 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 194QZ UT WOS:000322649100011 PM 23571836 ER PT J AU Schnabel, RB Rienstra, M Sullivan, LM Sun, JX Moser, CB Levy, D Pencina, MJ Fontes, JD Magnani, JW McManus, DD Lubitz, SA Tadros, TM Wang, TJ Ellinor, PT Vasan, RS Benjamin, EJ AF Schnabel, Renate B. Rienstra, Michiel Sullivan, Lisa M. Sun, Jenny X. Moser, Carlee B. Levy, Daniel Pencina, Michael J. Fontes, Joao D. Magnani, Jared W. McManus, David D. Lubitz, Steven A. Tadros, Thomas M. Wang, Thomas J. Ellinor, Patrick T. Vasan, Ramachandran S. Benjamin, Emelia J. TI Risk assessment for incident heart failure in individuals with atrial fibrillation SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Atrial fibrillation; Risk score; Epidemiology; Heart failure ID EJECTION FRACTION; ONSET; SURVIVAL; CARDIOVERSION; TRENDS AB Background Atrial fibrillation (AF) is a strong risk factor for heart failure (HF); HF onset in patients with AF is associated with increased morbidity and mortality. Risk factors that predict HF in individuals with AF in the community are not well established. Methods and results We examined clinical variables related to the 10-year incidence of HF in 725 individuals (mean 73.3 years, 45% women) with documented AF in the Framingham Heart Study. Event rates for incident HF (n = 161, 48% in women) were comparable in women (4.30 per 100 person-years) and men (3.34 per 100 person-years). Age, body mass index, ECG LV hypertrophy, diabetes, significant murmur, and history of myocardial infarction were positively associated with incident HF in multivariable models (C-statistic 0.71; 95% confidence interval 0.67-0.75). We developed a risk algorithm for estimating absolute risk of HF in AF patients with good model fit and calibration (adjusted calibration chi(2) statistic 7.29; P-chi 2 = 0.61). Applying the algorithm, 47.6% of HF events occurred in the top tertile in men compared with 13.1% in the bottom tertile, and 58.4% in women in the upper tertile compared with 18.2% in the lowest category. For HF type, women had a non-significantly higher incidence of HF with preserved EF compared with men. Conclusions We describe advancing age, LV hypertrophy, body mass index, diabetes, significant heart murmur, and history of myocardial infarction as clinical predictors of incident HF in individuals with AF. A risk algorithm may help identify individuals with AF at high risk of developing HF. C1 [Schnabel, Renate B.; Rienstra, Michiel; Pencina, Michael J.; Fontes, Joao D.; Magnani, Jared W.; McManus, David D.; Tadros, Thomas M.; Wang, Thomas J.; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBIs & Boston Univ Framingham Heart Study, Framingham, MA USA. [Schnabel, Renate B.] Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Sullivan, Lisa M.; Sun, Jenny X.; Moser, Carlee B.; Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Wang, Thomas J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Mem Med Dept, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Schnabel, RB (reprint author), Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Bldg East 70 O70,Martinistr 52, D-20246 Hamburg, Germany. EM schnabelr@gmx.de RI Schnabel, Renate/F-6527-2014; OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Institutes of Health (NIH)/National Heart Lung, and Blood Institute (NHLBI) [N01-HC-25195, 6R01-NS 17950]; NIH [HL092577-01A1, 1RC1HL101056, 1R01HL102214, 1R01AG028321, 5R21DA027021, 1RO1HL104156, 1K24HL105780, HL080124, HL077477, HL71039, 2K24 HL04334]; Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-1, SCHN 1149/3-1]; Netherlands Organization for Scientific Research [825.09.020]; Evans Center for Interdisciplinary Biomedical Research ARC on 'Atrial Fibrillation' at Boston University FX Supported by National Institutes of Health (NIH)/National Heart Lung, and Blood Institute (NHLBI) contract N01-HC-25195; 6R01-NS 17950; NIH grants HL092577-01A1 (P.T.E. and E.J.B.); 1RC1HL101056; 1R01HL102214; 1R01AG028321 (E.J.B.); 5R21DA027021, 1RO1HL104156, 1K24HL105780 (P.T.E.); HL080124, HL077477, and HL71039 (R.S.V.). NIH Research career award 2K24 HL04334 (R.S.V.); Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-1 and Emmy Noether Program (SCHN 1149/3-1) (R.B.S.); M.R. is supported by a grant from the Netherlands Organization for Scientific Research (Rubicon Grant 825.09.020). This work was partially supported by the Evans Center for Interdisciplinary Biomedical Research ARC on 'Atrial Fibrillation' at Boston University (http://www.bumc.bu.edu/evanscenteribr/) NR 26 TC 20 Z9 21 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD AUG PY 2013 VL 15 IS 8 BP 843 EP 849 DI 10.1093/eurjhf/hft041 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191CS UT WOS:000322390800004 PM 23594831 ER PT J AU Rabany, L Weiser, M Levkovitz, Y AF Rabany, L. Weiser, M. Levkovitz, Y. TI Guilt and depression: Two different factors in individuals with negative symptoms of schizophrenia SO EUROPEAN PSYCHIATRY LA English DT Article DE Schizophrenia; Calgary Depression Scale (CDSS); Depression; Factor analysis; Positive and Negative Symptom Scale (PANSS) ID 2ND-GENERATION ANTIPSYCHOTICS; SCALE; HALOPERIDOL; RISPERIDONE; INSIGHT; DEFICIT AB Objective: Depression is common among schizophrenia patients and constitutes a major risk factor for suicide. Calgary Depression Scale (CDSS) is the most widely used instrument for measuring depression in schizophrenia. CDSS has never been examined in patients with predominant negative symptoms, thus possibly hindering both accurate assessment and understanding of the underlying mechanisms. The current study is the first to examine CDSS' structure in this population. Methods: We conducted Principal Component Analysis (n = 184) for the CDSS items. Thereafter, we correlated emerging factors with psychopathological, demographic and side effect variables. We assessed internal consistency and reliability of the emerging factors, as well as demographic correlations. Results: The analysis yielded two factors: depression-hopelessness and guilt. Factors distinctly correlated with separate variables. Removal of item #7 (early waking) improved internal consistency. The depression-hopelessness factor had an inverse correlation with negative symptoms, and positive correlation with neuroleptic side effects. Conclusions: CDSS structure indicated of two separate factors, i.e., depression-hopelessness and guilt, suggesting separate underlying processes. The validity of the scale might benefit from a two-fold structure and the removal/replacement of item #7 (early waking). A noteworthy inverse correlation was found between the depression factor and negative symptoms, as well as a positive correlation between depression factor and neuroleptic side effects. (C) 2012 Published by Elsevier Masson SAS. C1 [Rabany, L.] Tel Aviv Univ, Gordon Fac Social Sci, IL-69978 Tel Aviv, Israel. [Rabany, L.; Weiser, M.; Levkovitz, Y.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Rabany, L.; Levkovitz, Y.] Shalvata Mental Hlth Care Ctr, Emot Cognit Res Ctr, Hod Hasharon, Israel. [Weiser, M.] Sheba Med Ctr, Dept Psychiat, Ramat Gan, Israel. [Levkovitz, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rabany, L (reprint author), Tel Aviv Univ, Gordon Fac Social Sci, IL-69978 Tel Aviv, Israel. EM lironrab@clalit.org.il NR 26 TC 2 Z9 2 U1 2 U2 7 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD AUG PY 2013 VL 28 IS 6 BP 327 EP 331 DI 10.1016/j.eurpsy.2012.02.008 PG 5 WC Psychiatry SC Psychiatry GA 194SA UT WOS:000322651800001 PM 23021933 ER PT J AU Zon, L AF Zon, Leonard TI MAKING AND IMPROVING THE FUNCTION OF ADULT BLOOD STEM CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 42nd Annual Scientific Meeting of the International-Society-for-Experimental-Hematology-and-Stem-Cells (ISEH) CY AUG 22-25, 2013 CL Vienna, AUSTRIA SP Int Soc Expt Hematol and Stem Cells (ISEH) C1 [Zon, Leonard] HHMI Boston Childrens Hosp, Stem Cell Program, Boston, MA USA. [Zon, Leonard] HHMI Boston Childrens Hosp, Boston, MA USA. [Zon, Leonard] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zon, Leonard] Harvard Stem Cell Inst, Boston, MA USA. [Zon, Leonard] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2013 VL 41 IS 8 SU 1 BP S2 EP S2 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 199VY UT WOS:000323024800002 ER PT J AU Shaheen, NJ Hur, C AF Shaheen, Nicholas J. Hur, Chin TI Garlic, Silver Bullets, and Surveillance Upper Endoscopy for Barrett's Esophagus SO GASTROENTEROLOGY LA English DT Editorial Material ID GASTROESOPHAGEAL-REFLUX DISEASE; TEMPORAL TRENDS; UNITED-STATES; ADENOCARCINOMA; MORTALITY; CANCER; POPULATION; COHORT; RISK; ACCEPTABILITY C1 Univ N Carolina, Ctr Esophageal Dis & Swallowing, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Gastrointestinal Unit, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Shaheen, NJ (reprint author), Univ N Carolina, Ctr Esophageal Dis & Swallowing, Sch Med, CB 7080, Chapel Hill, NC 27599 USA. OI Hur, Chin/0000-0002-2819-7576 NR 26 TC 7 Z9 7 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2013 VL 145 IS 2 BP 273 EP 276 DI 10.1053/j.gastro.2013.06.028 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 194KC UT WOS:000322630600009 PM 23806540 ER PT J AU Ellinghaus, D Zhang, H Zeissig, S Lipinski, S Till, A Jiang, T Stade, B Bromberg, Y Ellinghaus, E Keller, A Rivas, MA Skieceviciene, J Doncheva, NT Liu, X Liu, Q Jiang, FM Forster, M Mayr, G Albrecht, M Hasler, R Boehm, BO Goodall, J Berzuini, CR Lee, J Andersen, V Vogel, U Kupcinskas, L Kayser, M Krawczak, M Nikolaus, S Weersma, RK Ponsioen, CY Sans, M Wijmenga, C Strachan, DP McAardle, WL Vermeire, S Rutgeerts, P Sanderson, JD Mathew, CG Vatn, MH Wang, J Nothen, MM Duerr, RH Buning, C Brand, S Glas, J Winkelmann, J Illig, T Latiano, A Annese, V Halfvarson, J D'Amato, M Daly, MJ Nothnagel, M Karlsen, TH Subramani, S Rosenstiel, P Schreiber, S Parkes, M Franke, A AF Ellinghaus, David Zhang, Hu Zeissig, Sebastian Lipinski, Simone Till, Andreas Jiang, Tao Stade, Bjoern Bromberg, Yana Ellinghaus, Eva Keller, Andreas Rivas, Manuel A. Skieceviciene, Jurgita Doncheva, Nadezhda T. Liu, Xiao Liu, Qing Jiang, Fuman Forster, Michael Mayr, Gabriele Albrecht, Mario Haesler, Robert Boehm, Bernhard O. Goodall, Jane Berzuini, Carlo R. Lee, James Andersen, Vibeke Vogel, Ulla Kupcinskas, Limas Kayser, Manfred Krawczak, Michael Nikolaus, Susanna Weersma, Rinse K. Ponsioen, Cyriel Y. Sans, Miquel Wijmenga, Cisca Strachan, David P. McAardle, Wendy L. Vermeire, Severine Rutgeerts, Paul Sanderson, Jeremy D. Mathew, Christopher G. Vatn, Morten H. Wang, Jun Noethen, Markus M. Duerr, Richard H. Buening, Carsten Brand, Stephan Glas, Juergen Winkelmann, Juliane Illig, Thomas Latiano, Anna Annese, Vito Halfvarson, Jonas D'Amato, Mauro Daly, Mark J. Nothnagel, Michael Karlsen, Tom H. Subramani, Suresh Rosenstiel, Philip Schreiber, Stefan Parkes, Miles Franke, Andre TI Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies SO GASTROENTEROLOGY LA English DT Article DE Inflammatory Bowel Disease; Whole-Exome Sequencing; Complex Disease ID GENOME-WIDE ASSOCIATION; TRANSCRIPTIONAL REPRESSOR BLIMP-1; INFLAMMATORY-BOWEL-DISEASE; T-CELL HOMEOSTASIS; SUSCEPTIBILITY LOCI; LYMPHOCYTE MIGRATION; ULCERATIVE-COLITIS; AUTOPHAGY RECEPTOR; L-SELECTIN; EXPRESSION AB BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies. METHODS: We sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems. RESULTS: We identified rare missense mutations in PR domain-containing 1 (PRDM1) and associated these with CD. These mutations increased proliferation of T cells and secretion of cytokines on activation and increased expression of the adhesion molecule L-selectin. A common CD risk allele, identified in GWAS, correlated with reduced expression of PRDM1 in ileal biopsy specimens and peripheral blood mononuclear cells (combined P = 1.6 x 10(-8)). We identified an association between CD and a common missense variant, Val248Ala, in nuclear domain 10 protein 52 (NDP52) (P = 4.83 x 10(-9)). We found that this variant impairs the regulatory functions of NDP52 to inhibit nuclear factor kappa B activation of genes that regulate inflammation and affect the stability of proteins in Toll-like receptor pathways. CONCLUSIONS: We have extended the results of GWAS and provide evidence that variants in PRDM1 and NDP52 determine susceptibility to CD. PRDM1 maps adjacent to a CD interval identified in GWAS and encodes a transcription factor expressed by T and B cells. NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD. C1 [Ellinghaus, David; Lipinski, Simone; Stade, Bjoern; Ellinghaus, Eva; Forster, Michael; Haesler, Robert; Rosenstiel, Philip; Schreiber, Stefan; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany. [Krawczak, Michael; Nothnagel, Michael] Univ Kiel, Inst Med Informat & Stat, D-24105 Kiel, Germany. [Zhang, Hu; Lee, James; Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge CB2 2QQ, England. [Goodall, Jane] Univ Cambridge, Dept Med, Ctr Math Sci, Cambridge CB2 2QQ, England. [Berzuini, Carlo R.] Univ Cambridge, Stat Lab, Ctr Math Sci, Cambridge CB2 1SB, England. [Zhang, Hu] Sichuan Univ, West China Hosp, Dept Gastroenterol, Chengdu 610064, Peoples R China. [Zhang, Hu] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610064, Peoples R China. [Zeissig, Sebastian; Nikolaus, Susanna; Schreiber, Stefan] Univ Hosp Schleswig Holstein, Dept Internal Med, Kiel, Germany. [Krawczak, Michael] Univ Hosp Schleswig Holstein, PopGen Biobank, Kiel, Germany. [Till, Andreas; Subramani, Suresh] Univ Calif San Diego, Mol Biol Sect, La Jolla, CA 92093 USA. [Till, Andreas; Subramani, Suresh] San Diego Ctr Syst Biol, La Jolla, CA USA. [Jiang, Tao; Liu, Xiao; Liu, Qing; Jiang, Fuman; Wang, Jun] BGI Shenzhen, Shenzhen, Peoples R China. [Bromberg, Yana] Rutgers State Univ, Sch Environm & Biol Sci, Dept Biochem & Microbiol, New Brunswick, NJ 08903 USA. [Keller, Andreas] Univ Saarland, Dept Human Genet, Homburg, Germany. [Rivas, Manuel A.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Rivas, Manuel A.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Rivas, Manuel A.; Daly, Mark J.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. [Skieceviciene, Jurgita; Kupcinskas, Limas] Lithuanian Univ Hlth Sci, Inst Digest Res, Kaunas, Lithuania. [Doncheva, Nadezhda T.; Mayr, Gabriele; Albrecht, Mario] Max Planck Inst Informat, D-66123 Saarbrucken, Germany. [Albrecht, Mario] Univ Med Greifswald, Inst Biometr & Med Informat, Dept Bioinformat, Greifswald, Germany. [Boehm, Bernhard O.] Univ Med Ctr Ulm, Dept Internal Med 1, Div Endocrinol & Diabet, Ulm, Germany. [Boehm, Bernhard O.] Ctr Excellence Metab Disorders Baden Wurttemberg, Ulm, Germany. [Andersen, Vibeke] Viborg Reg Hosp, Dept Med, Viborg, Denmark. [Andersen, Vibeke] Aabenraa SHS, Dept Med, Aabenraa, Denmark. [Vogel, Ulla] Natl Res Ctr Working Environm, Copenhagen, Denmark. [Kayser, Manfred] Erasmus MC Univ, Med Ctr Rotterdam, Dept Forens Mol Biol, Rotterdam, Netherlands. [Weersma, Rinse K.] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol, NL-9713 AV Groningen, Netherlands. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Ponsioen, Cyriel Y.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Sans, Miquel] Ctr Med Teknon, Serv Digest Dis, Barcelona, Spain. [Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England. [McAardle, Wendy L.] Univ Bristol, Dept Social & Community Med, Avon Longitudinal Study Parents & Children Lab, Bristol, Avon, England. [Vermeire, Severine; Rutgeerts, Paul] Univ Hosp Gasthuisberg, Div Gastroenterol, B-3000 Louvain, Belgium. [Sanderson, Jeremy D.] Guys & St Thomas Natl Hlth Serv Fdn Trust, Dept Gastroenterol, London, England. [Mathew, Christopher G.] Kings Coll London, Div Genet & Mol Med, London, England. [Vatn, Morten H.] Univ Hosp, Rikshosp, Dept Med, Oslo, Norway. [Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Buening, Carsten] Charite, Dept Gastroenterol Hepatol & Endocrinol, Berlin, Germany. [Brand, Stephan; Glas, Juergen] Univ Munich, Dept Med 2, Munich, Germany. [Glas, Juergen] Univ Munich, Dept Prevent Dent & Periodontol, Munich, Germany. [Glas, Juergen] Rhein Westfal TH Aachen, Dept Human Genet, D-52062 Aachen, Germany. [Winkelmann, Juliane] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Human Genet, Neuherberg, Germany. [Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Res Unit Mol Epidemiol, Neuherberg, Germany. [Winkelmann, Juliane] Tech Univ Munich, MRI, Inst Human Genet, D-80290 Munich, Germany. [Winkelmann, Juliane] Tech Univ Munich, MRI, Dept Neurol, D-80290 Munich, Germany. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Latiano, Anna; Annese, Vito] Casa Sollievo Sofferenza Hosp, Ist Ricovero & Cura Carattere Sci, Div Gastroenterol, San Giovanni Rotondo, Italy. [Annese, Vito] Azienda Osped Univ Careggi, Unit Gastroenterol SOD2, Florence, Italy. [Halfvarson, Jonas] Univ Orebro, Orebro Univ Hosp, Div Gastroenterol, Orebro, Sweden. [Halfvarson, Jonas] Univ Orebro, Sch Hlth & Med Sci, Orebro, Sweden. [D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden. [Karlsen, Tom H.] Oslo Univ Hosp, Rigshosp, Norwegian PSC Res Ctr, Div Canc Surg & Transplantat, Oslo, Norway. [Karlsen, Tom H.] Univ Bergen, Fac Med & Dent, Inst Med, Bergen, Norway. RP Franke, A (reprint author), Univ Kiel, Inst Clin Mol Biol, Schittenhelmstr 12, D-24105 Kiel, Germany. EM a.franke@mucosa.de RI Krawczak, Michael/A-8964-2010; Schreiber, Stefan/B-6748-2008; Latiano, Anna/R-1965-2016; Ellinghaus, David/G-4467-2012; Hasler, Robert/A-4908-2009; Wijmenga, Cisca/D-2173-2009; Zeissig, Sebastian/B-6297-2012; Nothnagel, Michael/G-6545-2014; Albrecht, Mario/B-6694-2008; Boehm, Bernhard/F-8750-2015; Mathew, Christopher/G-3434-2015; Wang, Jun/C-8434-2016; Ellinghaus, Eva/E-6490-2012; Franke, Andre/B-2151-2010; Vogel, Ulla/I-5048-2012; Wang, Jun/B-9503-2016; OI Krawczak, Michael/0000-0003-2603-1502; Schreiber, Stefan/0000-0003-2254-7771; Latiano, Anna/0000-0003-3719-2061; Albrecht, Mario/0000-0002-3103-9624; Mathew, Christopher/0000-0003-4178-1838; Wang, Jun/0000-0002-8540-8931; Ellinghaus, Eva/0000-0003-2914-3382; Franke, Andre/0000-0003-1530-5811; Nothen, Markus/0000-0002-8770-2464; Lee, James/0000-0001-5711-9385; Bromberg, Yana/0000-0002-8351-0844; Halfvarson, Jonas/0000-0003-0122-7234; , Andreas/0000-0002-5361-0895; Andersen, Vibeke/0000-0002-0127-2863; Duerr, Richard/0000-0001-6586-3905; Vogel, Ulla/0000-0001-6807-1524; Vermeire, Severine/0000-0001-9942-3019; Wang, Jun/0000-0002-2113-5874; Winkelmann, Juliane/0000-0003-2667-9691; Wijmenga, Cisca/0000-0002-5635-1614; Rosenstiel, Philip/0000-0002-9692-8828; D'Amato, Mauro/0000-0003-2743-5197 FU Deutsche Forschungsgemeinschaft (DFG) [FR 2821/2-1, Ti 640 1-1, SFB 877]; German Ministry of Education and Research through the National Genome Research Network; PopGen biobank; National Institutes of Health [GM069373, 1R01CA141743-01]; DFG [BR1912/6-1, ZE 814/4-1, ZE 814/5-1]; Else-Kroner-Fresenius-Stiftung [2010_EKES.32]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; National Institute for Health Research Biomedical Research Centre; San Diego Center for Systems Biology; University of Pittsburgh Genomics and Proteomics Core Laboratories for the ImmunoChip genotyping services; Swedish Research Council (VR) FX Supported by Deutsche Forschungsgemeinschaft (DFG) grant FR 2821/2-1 and research fellowship Ti 640 1-1, the SFB 877 subproject B9, the German Ministry of Education and Research through the National Genome Research Network, the PopGen biobank (http://www.popgen.de), and the National Institutes of Health (grant GM069373). The project received infrastructure support through the DFG Clusters of Excellence "Inflammation at Interfaces" and "Multimodal Computing and Interaction." S. Brand is supported by DFG grant BR1912/6-1 and by the Else-Kroner-Fresenius-Stiftung (stipend 2010_EKES.32). The authors acknowledge use of material from the British 1958 Birth Cohort DNA collection, funded by Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02 (http://www.b58cgene.sgul.ac.uk/). The authors also acknowledge the participation of all Cambridge BioResource subjects and staff (http://www.cambridgebioresource.org.uk/); the National Institute for Health Research Biomedical Research Centre awards to Guy's & St Thomas' National Health Service Trust/King's College London and to Addenbrooke's Hospital/University of Cambridge School of Clinical Medicine; the Wellcome Trust Case Control Consortium, a seed grant from the San Diego Center for Systems Biology (to A. Till and S. Subramani), National Institutes of Health grant 1R01CA141743-01 (principal investigator: R. H. Duerr), the University of Pittsburgh Genomics and Proteomics Core Laboratories for the ImmunoChip genotyping services, and DFG grants ZE 814/4-1 and ZE 814/5-1 (to S. Zeissig). M. D'Amato received support from the Swedish Research Council (VR). NR 32 TC 54 Z9 54 U1 2 U2 31 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 AUG PY 2013 VL 145 IS 2 BP 339 EP 347 DI 10.1053/j.gastro.2013.04.040 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 194KC UT WOS:000322630600023 PM 23624108 ER PT J AU Wang, FC Scoville, D He, XC Mahe, MM Box, A Perry, JM Smith, NR Lei, NY Davies, PS Fuller, MK Haug, JS McClain, M Gracz, AD Ding, S Stelzner, M Dunn, JCY Magness, ST Wong, MH Martin, MG Helmrath, M Li, LH AF Wang, Fengchao Scoville, David He, Xi C. Mahe, Maxime M. Box, Andrew Perry, John M. Smith, Nicholas R. Lei, Nan Ye Davies, Paige S. Fuller, Megan K. Haug, Jeffrey S. McClain, Melainia Gracz, Adam D. Ding, Sheng Stelzner, Matthias Dunn, James C. Y. Magness, Scott T. Wong, Melissa H. Martin, Martin G. Helmrath, Michael Li, Linheng TI Isolation and Characterization of Intestinal Stem Cells Based on Surface Marker Combinations and Colony-Formation Assay SO GASTROENTEROLOGY LA English DT Article DE Stemness; Differentiation; Single-Cell Sorting; Flow Cytometry Analysis ID MOUSE SMALL-INTESTINE; SELF-RENEWAL; IN-VITRO; EXPRESSION MARKS; EPITHELIAL-CELLS; LGR5; POPULATIONS; EXPANSION; IDENTIFICATION; ORGANOIDS AB BACKGROUND & AIMS: Identification of intestinal stem cells (ISCs) has relied heavily on the use of transgenic reporters in mice, but this approach is limited by mosaic expression patterns and difficult to directly apply to human tissues. We sought to identify reliable surface markers of ISCs and establish a robust functional assay to characterize ISCs from mouse and human tissues. METHODS: We used immunohistochemistry, real-time reverse-transcription polymerase chain reaction, and fluorescence-activated cell sorting (FACS) to analyze intestinal epithelial cells isolated from mouse and human intestinal tissues. We compared different combinations of surface markers among ISCs isolated based on expression of Lgr5-green fluorescent protein. We developed a culture protocol to facilitate the identification of functional ISCs from mice and then tested the assay with human intestinal crypts and putative ISCs. RESULTS: CD44(+)CD24(lo)CD166(+) cells, isolated by FACS from mouse small intestine and colon, expressed high levels of stem cell-associated genes. Transit-amplifying cells and progenitor cells were then excluded based on expression of GRP78 or c-Kit. CD44(+)CD24(lo)CD166(+) GRP78(lo/-) putative stem cells from mouse small intestine included Lgr5-GFP(hi) and Lgr5-GFP(med/lo) cells. Incubation of these cells with the GSK inhibitor CHIR99021 and the E-cadherin stabilizer Thiazovivin resulted in colony formation by 25% to 30% of single-sorted ISCs. CONCLUSIONS: We developed a culture protocol to identify putative ISCs from mouse and human tissues based on cell surface markers. CD44(+)CD24(lo)CD166(+) , GRP78(lo/-), and c-Kit L facilitated identification of putative stem cells from the mouse small intestine and colon, respectively. CD44(+)CD24(-/lo)CD166(+) also identified putative human ISCs. These findings will facilitate functional studies of mouse and human ISCs. C1 [Wang, Fengchao; He, Xi C.; Box, Andrew; Perry, John M.; Haug, Jeffrey S.; McClain, Melainia; Li, Linheng] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Scoville, David; Li, Linheng] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66103 USA. [Mahe, Maxime M.; Fuller, Megan K.; Helmrath, Michael] Cincinnati Childrens Hosp Med Res Ctr, Cincinnati, OH USA. [Smith, Nicholas R.; Davies, Paige S.; Wong, Melissa H.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Lei, Nan Ye; Martin, Martin G.] Univ Calif Los Angeles, Dept Pediat, Div Gastroenterol, Los Angeles, CA 90024 USA. [Stelzner, Matthias; Dunn, James C. Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Fuller, Megan K.; Gracz, Adam D.; Magness, Scott T.] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol Cell Biol & Physiol &, Chapel Hill, NC USA. [Fuller, Megan K.; Gracz, Adam D.; Magness, Scott T.] Univ N Carolina, Dept Surg, Chapel Hill, NC USA. [Ding, Sheng] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA. [Stelzner, Matthias] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Magness, Scott T.; Wong, Melissa H.; Martin, Martin G.; Li, Linheng] Intestinal Stem Cell Consortium, Duarte, CA USA. RP Li, LH (reprint author), Stowers Inst Med Res, 1000 East 50th St, Kansas City, MO 64110 USA. EM lil@stowers.org OI Mahe, Maxime/0000-0003-2560-193X FU Intestinal Stem Cell Consortium [U01DK085507, U01DK85525, U01DK85535, U01DK085547, U01DK85532]; Stowers Institute for Medical Research FX This research was performed as a project of the Intestinal Stem Cell Consortium, L. Li (U01DK085507), M. H. Wong (U01DK85525), M. Martin (U01DK85535), S. T. Magness (U01DK085547: SJH/STM), and the Coordinating Center J. Niland (U01DK85532). L. Li is supported in part by Stowers Institute for Medical Research. NR 36 TC 53 Z9 54 U1 4 U2 33 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 AUG PY 2013 VL 145 IS 2 BP 383 EP + DI 10.1053/j.gastro.2013.04.050 PG 34 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 194KC UT WOS:000322630600028 PM 23644405 ER PT J AU Burks, ML Kundrotas, L AF Burks, Margaret L. Kundrotas, Leon TI Unusual Colon Biopsy SO GASTROENTEROLOGY LA English DT Editorial Material ID SPIROCHETOSIS C1 [Burks, Margaret L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kundrotas, Leon] South Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Gastroenterol, San Antonio, TX USA. RP Burks, ML (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2013 VL 145 IS 2 BP E10 EP E11 DI 10.1053/j.gastro.2013.04.054 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 194KC UT WOS:000322630600005 PM 23810345 ER PT J AU Fogel, BL Vickrey, BG Walton-Wetzel, J Lieber, E Browner, CH AF Fogel, Brent L. Vickrey, Barbara G. Walton-Wetzel, Jenny Lieber, Eli Browner, Carole H. TI Utilization of Genetic Testing Prior to Subspecialist Referral for Cerebellar Ataxia SO GENETIC TESTING AND MOLECULAR BIOMARKERS LA English DT Article ID LATE-ONSET CEREBELLAR; CLINICAL-FEATURES; CARE; NEUROLOGISTS; INVOLVEMENT AB Objective: To evaluate the utilization of laboratory testing in the diagnosis of cerebellar ataxia, including the completeness of initial standard testing for acquired causes, the early use of genetic testing, and associated clinical and nonclinical factors, among a cohort referred for subspecialty consultation. Methods: Data were abstracted from records of 95 consecutive ataxia patients referred to one neurogenetics subspecialist from 2006-2010 and linked to publicly available data on characteristics of referral clinicians. Multivariable logistic and linear regression models were used to analyze unique associations of clinical and nonclinical factors with laboratory investigation of acquired causes and with early genetic testing prior to referral. Results: At referral, 27 of 95 patients lacked evidence of any of 14 laboratory studies suggested for initial work-up of an acquired cause for ataxia (average number of tests = 4.5). In contrast, 92% of patients had undergone brain magnetic resonance imaging prior to referral. Overall, 41.1% (n = 39) had genetic testing prior to referral; there was no association between family history of ataxia and obtaining genetic testing prior to referral (p = 0.39). The level of early genetic testing was 31.6%, primarily due to genetic testing despite an incomplete laboratory evaluation for acquired causes and no family history. A positive family history was consistently associated with less extensive laboratory testing (p = 0.004), and referral by a neurologist was associated with higher levels of early genetic testing. Conclusions: Among consecutive referrals to a single center, a substantial proportion of sporadic cases had genetic testing without evidence of a work-up for acquired causes. Better strategies to guide decision making and subspecialty referrals in rare neurologic disorders are needed, given the cost and consequences of genetic testing. C1 [Fogel, Brent L.; Vickrey, Barbara G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Vickrey, Barbara G.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. [Walton-Wetzel, Jenny; Browner, Carole H.] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90024 USA. [Lieber, Eli; Browner, Carole H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Browner, CH (reprint author), UCLA Psychiat & Biobehav Sci Anthropol, David Geffen Sch Med, Box 951553,347 Haines Hall, Los Angeles, CA 90095 USA. EM browner@ucla.edu FU NIMH [K08MH86297]; UCLA Committee on Research Faculty Research Grant FX The authors acknowledge the contribution of the following individuals: Stefanie D. Vassar, MS for assistance with statistical analysis, and Jacob Foreman and Kelly Hitch for assistance with data collection. Support provided by NIMH K08MH86297 (B. L. F.), UCLA Committee on Research Faculty Research Grant (C. H. B.). NR 20 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1945-0265 J9 GENET TEST MOL BIOMA JI Genet. Test. Mol. Biomark. PD AUG PY 2013 VL 17 IS 8 BP 588 EP 594 DI 10.1089/gtmb.2013.0005 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 194IH UT WOS:000322624500003 PM 23725007 ER PT J AU Sun, D Qu, J Jakobs, TC AF Sun, Daniel Qu, Juan Jakobs, Tatjana C. TI Reversible reactivity by optic nerve astrocytes SO GLIA LA English DT Article DE white matter; fibrous astrocytes; glaucoma; glial remodeling ID FIBRILLARY ACIDIC PROTEIN; ELEVATED INTRAOCULAR-PRESSURE; GANGLION-CELL DEGENERATION; SPINAL-CORD-INJURY; MOUSE MODEL; OCULAR HYPERTENSION; TRANSGENIC MICE; DBA/2J MICE; PHOSPHORYLATION SITES; AXONAL-TRANSPORT AB Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. Here, we evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling that peaked at three days, showing hypertrophy, process retraction, and simplification of their shape. This was not accompanied by any significant changes in the gene expression profile. At no time was there discernible damage to the optic axons, as evidenced by electron microscopy and normal anterograde and retrograde transport. Remarkably, the morphological remodeling was reversible. These findings underscore the plastic nature of reactivity. They show that reactivity can resolve fully if the insult is removed, and suggest that reactivity per se is not necessarily deleterious to axons. This reaction may represent very early events in the sequence that eventually leads to glial scarring. GLIA 2013;61:1218-1235 C1 [Sun, Daniel; Qu, Juan; Jakobs, Tatjana C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Jakobs, TC (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM tatjana_jakobs@meei.harvard.edu OI Jakobs, Tatjana/0000-0002-8104-9206 FU National Institute of Health [RO1 EY019703, RO1 EY13399, EY14104]; Research to Prevent Blindness; Massachusetts Lions Eye Research Fund FX Grant sponsor: National Institute of Health; Grant numbers: RO1 EY019703, RO1 EY13399, EY14104 (Core grant to MEEI); Grant sponsors: Research to Prevent Blindness, Massachusetts Lions Eye Research Fund. NR 63 TC 26 Z9 27 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-1491 J9 GLIA JI Glia PD AUG PY 2013 VL 61 IS 8 BP 1218 EP 1235 DI 10.1002/glia.22507 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 185PY UT WOS:000321983400003 PM 23650091 ER PT J AU Kim, HY Chang, YJ Chuang, YT Lee, HH Kasahara, DI Martin, T Hsu, JT Savage, PB Shore, SA Freeman, GJ DeKruyff, RH Umetsu, DT AF Kim, Hye Young Chang, Ya-Jen Chuang, Ya-Ting Lee, Hyun-Hee Kasahara, David I. Martin, Thomas Hsu, Joyce T. Savage, Paul B. Shore, Stephanie A. Freeman, Gordon J. DeKruyff, Rosemarie H. Umetsu, Dale T. TI T-cell immunoglobulin and mucin domain 1 deficiency eliminates airway hyperreactivity triggered by the recognition of airway cell death SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE TIM-1; natural killer T; apoptosis; asthma ID RESPIRATORY SYNCYTIAL VIRUS; HEPATITIS-A VIRUS; ADAPTIVE IMMUNITY; CHILDHOOD ASTHMA; GENETIC-VARIANTS; APOPTOTIC CELLS; ALLERGIC-ASTHMA; MOUSE MODEL; NKT CELLS; IN-VIVO AB Background: Studies of asthma have been limited by a poor understanding of how nonallergic environmental exposures, such as air pollution and infection, are translated in the lung into inflammation and wheezing. Objective: Our goal was to understand the mechanism of nonallergic asthma that leads to airway hyperreactivity (AHR), a cardinal feature of asthma independent of adaptive immunity. Method: We examined mouse models of experimental asthma in which AHR was induced by respiratory syncytial virus infection or ozone exposure using mice deficient in T-cell immunoglobulin and mucin domain 1 (TIM1/HAVCR1), an important asthma susceptibility gene. Results: TIM1(-/-) mice did not have airways disease when infected with RSVor when repeatedly exposed to ozone, a major component of air pollution. On the other hand, the TIM1(-/-) mice had allergen-induced experimental asthma, as previously shown. The RSV-and ozone-induced pathways were blocked by treatment with caspase inhibitors, indicating an absolute requirement for programmed cell death and apoptosis. TIM-1-expressing, but not TIM-1-deficient, natural killer T cells responded to apoptotic airway epithelial cells by secreting cytokines, which mediated the development of AHR. Conclusion: We defined a novel pathway in which TIM-1, a receptor for phosphatidylserine expressed by apoptotic cells, drives the development of asthma by sensing and responding to injured and apoptotic airway epithelial cells. C1 [Kim, Hye Young; Chang, Ya-Jen; Chuang, Ya-Ting; Lee, Hyun-Hee; Hsu, Joyce T.; DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Univ, Sch Med, Childrens Hosp, Div Immunol & Allergy, Boston, MA 02115 USA. [Kasahara, David I.; Shore, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA. [Martin, Thomas] Harvard Univ, Sch Med, Childrens Hosp, Div Resp Dis, Boston, MA 02115 USA. [Savage, Paul B.] Brigham Young Univ, Provo, UT 84602 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Umetsu, DT (reprint author), Harvard Univ, Sch Med, Div Immunol, Childrens Hosp,Karp Labs, Rm 10127,1 Blackfan Circle, Boston, MA 02115 USA. EM dale.umetsu@childrens.harvard.edu FU Boston Children's Hospital; National Institutes ofHealth (NIH); McGill University; NIH; NIH/National Institute of Allergy and Infectious Diseases; CoStim; Genentech FX J. T. Hsu has received research support from Boston Children's Hospital and has received travel support from the Pediatric Academic Societies. S. A. Shore is employed by Harvard University; has received research support fromthe National Institutes ofHealth (NIH); and has received lecture fees fromtheChristie Lecture, McGill University. G. J. Freeman has received research support fromthe NIH and has patents on TIM molecules. R. H. DeKruyff has received research support from the NIH/National Institute of Allergy and Infectious Diseases, has patents on TIM molecule function, and receives royalties from Patent licensing. D. T. Umetsu has received research support from CoStim and Genentech, has patents on TIM molecules and other molecules, and receives royalties from patents on natural killer T cells. The rest of the authors declare that they have no relevant conflicts of interest. NR 57 TC 6 Z9 7 U1 0 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2013 VL 132 IS 2 BP 414 EP + DI 10.1016/j.jaci.2013.03.025 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA 194KL UT WOS:000322631700020 PM 23672783 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2013 VL 115 IS 3 BP 295 EP 296 DI 10.1152/japplphysiol.00565.2013 PG 2 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195PF UT WOS:000322715000001 PM 23703118 ER PT J AU Januzzi, JL AF Januzzi, James L., Jr. TI ST2 as a Cardiovascular Risk Biomarker: From the Bench to the Bedside SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Biomarker; Prognosis; Heart failure; Acute myocardial infarction ID RECEPTOR FAMILY-MEMBER; DECOMPENSATED HEART-FAILURE; VENTRICULAR SYSTOLIC DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; SERUM-SOLUBLE ST2; INTERLEUKIN-1 RECEPTOR; NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT; 1-YEAR MORTALITY; PLASMA-CONCENTRATIONS AB ST2 is a member of the interleukin (IL)-1 receptor family discovered in a classical translational science fashion, and exists in two forms, a trans-membrane receptor (ST2L) as well as a soluble decoy receptor (sST2). The ligand of ST2 is IL-33, which is involved in reducing fibrosis and hypertrophy in mechanically strained tissues. In in vitro and in vivo models, ST2L transduces the effects of IL-33, while excess sST2 or abnormalities in ST2 signaling leads to cardiac hypertrophy, fibrosis, and ventricular dysfunction. Clinically, in patients with symptomatic heart failure (HF), elevated concentrations of sST2 are strongly associated with severity of the diagnosis, and powerfully predict increased risk of complications, independent of other established or emerging biomarkers. sST2 testing has also been shown to predict onset of symptomatic HF in patients with acute myocardial infarction, while in community-based subjects, sST2 values independently predict future HF, cardiovascular disease events, and mortality. C1 Harvard Univ, Sch Med, Div Cardiol, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Harvard Univ, Sch Med, Div Cardiol, Dept Med,Massachusetts Gen Hosp, 32 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Critical Diagnostics; Roche Diagnostics; Siemens; BG Medicine; Thermo-Fisher FX Dr. Januzzi has received grant support from Critical Diagnostics, Roche Diagnostics, Siemens, BG Medicine, and Thermo-Fisher. NR 38 TC 24 Z9 25 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD AUG PY 2013 VL 6 IS 4 SI SI BP 493 EP 500 DI 10.1007/s12265-013-9459-y PG 8 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 184DV UT WOS:000321868500006 PM 23558647 ER PT J AU Yanamadala, V Sheth, SA Walcott, BP Buchbinder, BR Buckley, D Ogilvy, CS AF Yanamadala, Vijay Sheth, Sameer A. Walcott, Brian P. Buchbinder, Bradley R. Buckley, Deidre Ogilvy, Christopher S. TI Non-contrast 3D time-of-flight magnetic resonance angiography for visualization of intracranial aneurysms in patients with absolute contraindications to CT or MRI contrast SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Aneurysm; Contrast; Intracranial; MRI; Pregnancy; Time of flight ID ARTERIOVENOUS-MALFORMATIONS; PREGNANCY; MEDIA; EXPOSURE; DISEASE AB The preoperative evaluation of patients with intracranial aneurysms typically includes a contrast-enhanced vascular study, such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography. However, there are numerous absolute and relative contraindications to the administration of imaging contrast agents, including pregnancy, severe contrast allergy, and renal insufficiency. Evaluation of patients with contrast contraindications thus presents a unique challenge. We identified three patients with absolute contrast contraindications who presented with intracranial aneurysms. One patient was pregnant, while the other two had previous severe anaphylactic reactions to iodinated contrast. Because of these contraindications to intravenous contrast, we performed non-contrast time-of-flight MRA with 3D reconstruction (TOF MRA with 3DR) with maximum intensity projections and volume renderings as part of the preoperative evaluation prior to successful open surgical clipping of the aneurysms. In the case of one paraclinoid aneurysm, a high-resolution non-contrast CT scan was also performed to assess the relationship of the aneurysm to the anterior clinoid process. TOF MRA with 3DR successfully identified the intracranial aneurysms and adequately depicted the surrounding microanatomy. Intraoperative findings were as predicted by the preoperative imaging studies. The aneurysms were successfully clip-obliterated, and the patients had uneventful post-operative courses. These cases demonstrate that non-contrast imaging is a viable modality to assess intracranial aneurysms as part of the surgical planning process in patients with contrast contraindications. TOF MRA with 3DR, in conjunction with high-resolution non-contrast CT when indicated, provides adequate visualization of the microanatomy of the aneurysm and surrounding structures. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Yanamadala, Vijay; Sheth, Sameer A.; Walcott, Brian P.; Buckley, Deidre; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Buchbinder, Bradley R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yanamadala, Vijay; Sheth, Sameer A.; Walcott, Brian P.; Buchbinder, Bradley R.; Buckley, Deidre; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R25 NS065743] NR 27 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD AUG PY 2013 VL 20 IS 8 BP 1122 EP 1126 DI 10.1016/j.jocn.2012.12.005 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 192QM UT WOS:000322500300015 PM 23685107 ER PT J AU Jan, TA Redjal, N Walcott, BP Sheth, SA AF Jan, Taha A. Redjal, Navid Walcott, Brian P. Sheth, Sameer A. TI Intranasal myiasis: A rare complication of transnasal skull base surgery SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Brain infection; Endoscopic; Endonasal; Maggot; Myiasis; Transnasal; Skull base AB A 57-year-old woman with a history of atypical intracranial meningioma had undergone multiple craniotomies and endoscopic skull base procedures over several years. She presented most recently with nasal discharge consisting of intranasal larvae. Isolated organisms from the nasal cavity and maxillary sinus were identified as blow fly larvae (Calliphoridae family). The patient was treated with transnasal debridement and antibiotic therapy. The organisms were successfully eradicated and she is free from further signs of infection. Intranasal myiasis is an unusual complication of anterior skull base surgery. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Jan, Taha A.] Massachusetts Gen Hosp, Dept Otolaryngol, Boston, MA 02114 USA. [Jan, Taha A.; Redjal, Navid; Walcott, Brian P.; Sheth, Sameer A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Redjal, Navid; Walcott, Brian P.; Sheth, Sameer A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD AUG PY 2013 VL 20 IS 8 BP 1178 EP 1180 DI 10.1016/j.jocn.2012.09.028 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 192QM UT WOS:000322500300033 PM 23669173 ER PT J AU Stuart, GL Moore, TM Elkins, SR O'Farrell, TJ Temple, JR Ramsey, SE Shorey, RC AF Stuart, Gregory L. Moore, Todd M. Elkins, Sara R. O'Farrell, Timothy J. Temple, Jeff R. Ramsey, Susan E. Shorey, Ryan C. TI The Temporal Association Between Substance Use and Intimate Partner Violence Among Women Arrested for Domestic Violence SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE intimate partner violence; substance abuse; alcohol use; drug use ID ALCOHOL-RELATED AGGRESSION; OF-THE-LITERATURE; RISK-FACTORS; INTERVENTION PROGRAMS; CONCEPTUAL-FRAMEWORK; COLLEGE-STUDENTS; ABUSE; DRINKING; MEN; VICTIMIZATION AB Objective: There is a paucity of research on the temporal association between substance use and intimate partner violence (TV) perpetration and victimization, especially among women arrested for domestic violence. The current study examined whether the probability of IPV perpetration and victimization increases following alcohol or drug use relative to days of no use among women arrested for domestic violence. Method: Women arrested for domestic violence and court referred to batterer intervention programs who met criteria for hazardous drinking participated in the current study (N = 105). Women who reported drinking 4 or more drinks on 1 occasion at least once per month for the past 6 months were considered hazardous drinkers. Violence and substance use were assessed with the Timeline Followback Interviews for substance use and IPV. Results: Women were more likely to perpetrate physical violence on a drinking day (OR = 10.58; 95% CI [5.38, 20.79]) and on a heavy drinking day (OR = 12.81; 95% CI [8.10, 33.57]), relative to a nondrinking day. Women were more likely to be victimized by physical violence on a drinking day (OR = 5.22; 95% CI [2.79, 9.77]) and on a heavy drinking day (OR = 6.16; 95% CI [3.25, 11.68]), relative to a nondrinking day. They were more likely to be victims of sexual coercion (OR = 6.06; 95% CI [1.19, 30.80]) on a cocaine use day relative to a nonuse day. Conclusions: Alcohol use was temporally associated with physical violence perpetration and victimization, and cocaine use was temporally associated with sexual coercion victimization, suggesting that substance use should be targeted in batterer intervention programs for women. C1 [Stuart, Gregory L.] Univ Tennessee, Dept Psychol, Dept Psychiat & Human Behav, Knoxville, TN 37996 USA. [Stuart, Gregory L.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Stuart, Gregory L.] Butler Hosp, Providence, RI 02906 USA. [Stuart, Gregory L.; Moore, Todd M.; Elkins, Sara R.; Shorey, Ryan C.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [O'Farrell, Timothy J.] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. [O'Farrell, Timothy J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Temple, Jeff R.] Univ Texas Med Branch Galveston, Dept Obstet & Gynecol, Galveston, TX USA. [Ramsey, Susan E.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Stuart, GL (reprint author), Univ Tennessee, Dept Psychol, 310C Austin Peay Bldg, Knoxville, TN 37996 USA. EM gstuart@utk.edu RI Temple, Jeff/A-7666-2009 OI Temple, Jeff/0000-0003-3193-0510 FU NIAAA NIH HHS [K24 AA019707, K24AA019707, R01 AA016315, R01AA016315] NR 56 TC 25 Z9 25 U1 0 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2013 VL 81 IS 4 BP 681 EP 690 DI 10.1037/a0032876 PG 10 WC Psychology, Clinical SC Psychology GA 190PQ UT WOS:000322353100010 PM 23647284 ER PT J AU Hansen, LO Greenwald, JL Budnitz, T Howell, E Halasyamani, L Maynard, G Vidyarthi, A Coleman, EA Williams, MV AF Hansen, Luke O. Greenwald, Jeffrey L. Budnitz, Tina Howell, Eric Halasyamani, Lakshmi Maynard, Greg Vidyarthi, Arpana Coleman, Eric A. Williams, Mark V. TI Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID PATIENTS AFTER-DISCHARGE; QUALITY IMPROVEMENT; ADVERSE EVENTS; PATIENT SAFETY; CARE; CONTINUITY; PROGRAM; SCIENCE AB BACKGROUND: Rehospitalization is a prominent target for healthcare quality improvement and performance-based reimbursement. The generalizability of existing evidence on best practices is unknown. OBJECTIVE: To determine the effect of Project BOOST (Better Outcomes for Older adults through Safe Transitions) on rehospitalization rates and length of stay. DESIGN: Semicontrolled pre-post study. SETTING/PARTICIPANTS: Volunteer sample of 11 hospitals varying in geography, size, and academic affiliation. INTERVENTION: Hospitals implemented Project BOOST-recommended tools supported by an external quality improvement physician mentor. METHODS: Pre-post changes in readmission rates and length of stay within BOOST units, and between BOOST units and site-designated control units. RESULTS: The average rate of 30-day rehospitalization in BOOST units was 14.7% prior to implementation and 12.7% 12 months later (P = 0.010), reflecting an absolute reduction of 2% and a relative reduction of 13.6%. Rehospitalization rates for matched control units were 14.0% in the preintervention period and 14.1% in the postintervention period (P = 0.831). The mean absolute reduction in readmission rates in BOOST units compared to control units was 2.0% (P = 0.054 for signed rank test comparing differences in readmission rate reduction in BOOST units compared to site-matched control units). CONCLUSIONS: Participation in Project BOOST appeared to be associated with a decrease in readmission rates. (C) 2013 Society of Hospital Medicine C1 [Hansen, Luke O.; Williams, Mark V.] Northwestern Univ, Feinberg Sch Med, Div Hosp Med, Dept Med, Chicago, IL 60611 USA. [Greenwald, Jeffrey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Inpatient Clinician Educ Serv, Boston, MA USA. [Budnitz, Tina; Maynard, Greg] Soc Hosp Med, Philadelphia, PA USA. [Howell, Eric] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Halasyamani, Lakshmi] St Joseph Mercy Hlth Syst, Ypsilanti, MI USA. [Maynard, Greg] Univ Calif San Diego, Dept Med, San Diego Sch Med, San Diego, CA 92103 USA. [Vidyarthi, Arpana] SingHealth, Healthcare Leadership Coll, Singapore, Singapore. [Vidyarthi, Arpana] Duke NUS Grad Med Sch, Singapore, Singapore. [Coleman, Eric A.] Univ Colorado, Dept Med, Denver, CO USA. RP Williams, MV (reprint author), Northwestern Univ, Feinberg Sch Med, Div Hosp Med, 211 East Ontario St,Suite 700, Chicago, IL 60611 USA. EM markwill@nmh.org FU John A. Hartford Foundation; John A. Harford Foundation; SHM FX Project BOOST was funded by a grant from The John A. Hartford Foundation. Project BOOST is administered by the Society of Hospital Medicine (SHM). The development of the Project BOOST toolkit, recruitment of sites for this study, mentorship of the pilot cohort, project evaluation planning, and collection of pilot data were funded by a grant from The John A. Harford Foundation. Additional funding for continued data collection and analysis was funded by the SHM through funds from hospitals to participate in Project BOOST, specifically with funding support for Dr. Hansen. Dr. Williams has received funding to serve as Principal Investigator for Project BOOST. Since the time of initial cohort participation, approximately 125 additional hospitals have participated in the mentored implementation of Project BOOST. This participation was funded through a combination of site-based tuition, third-party payor support from private insurers, foundations, and federal funding through the Center for Medicare and Medicaid Innovation Partnership for Patients program. Drs. Greenwald, Hansen, and Williams are Project BOOST mentors for current Project BOOST sites and receive financial support through the SHM for this work. Dr. Howell has previously received funding as a Project BOOST mentor. Ms. Budnitz is the BOOST Project Director and is Chief Strategy and Development Officer for the HM. Dr. Maynard is the Senior Vice President of the SHM's Center for Hospital Innovation and Improvement. NR 19 TC 70 Z9 70 U1 2 U2 16 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 AUG PY 2013 VL 8 IS 8 BP 421 EP 427 DI 10.1002/jhm.2054 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 196QU UT WOS:000322791400001 PM 23873709 ER PT J AU Lindenauer, PK Grosso, LM Wang, CQ Wang, Y Krishnan, JA Lee, TA Au, DH Mularski, RA Bernheim, SM Drye, EE AF Lindenauer, Peter K. Grosso, Laura M. Wang, Changqin Wang, Yun Krishnan, Jerry A. Lee, Todd A. Au, David H. Mularski, Richard A. Bernheim, Susannah M. Drye, Elizabeth E. TI Development, validation, and results of a risk-standardized measure of hospital 30-day mortality for patients with exacerbation of chronic obstructive pulmonary disease SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID QUALITY-OF-CARE; HEART-FAILURE; PERFORMANCE; OUTCOMES; COPD; MODELS; DEATH; RATES AB BACKGROUND: Despite its large clinical and economic significance, measuring and improving the outcomes of patients hospitalized for chronic obstructive pulmonary disease (COPD) is only beginning to emerge as a national priority for policy makers and payers. OBJECTIVE: To facilitate the public reporting of hospital outcomes, we developed a risk-standardized measure of hospital 30-day mortality for patients admitted with exacerbation of COPD. DESIGN: Hierarchical logistic regression model. SETTING/PATIENTS: Medicare Part A and Part B claims in a random sample of half of all admissions for patients admitted to acute care hospitals in 2008 (development cohort) and remaining 2008 admissions (validation cohort). We also assessed model performance and predictive ability in 2007 and 2009 data. MEASUREMENTS: Hospital risk-standardized 30-day mortality rates. RESULTS: The model development sample consisted of 150,035 admissions at 4537 nonfederal acute care US hospitals, with a mean unadjusted hospital 30-day mortality rate of 8.6%. The mean risk-standardized mortality rate was 8.6% and ranged from 5.9% to 13.5%. The development and validation models had good discrimination (areas under the receiver operating characteristic curve 0.72 and 0.72, respectively) and predictive ability (predicted mortality at the 1st and 10th deciles 1.5%, 23.7%, and 1.6%, 23.8%, respectively) and showed no evidence of over-fitting. CONCLUSIONS: A 30-day mortality model based on administrative claims had similar discrimination to other public reporting models and can be used to compare riskadjusted outcomes for patients with exacerbations of COPD and to track changes in outcomes over time. The high mortality and variation in rates across institutions suggest opportunities to improve quality of care. Journal of Hospital Medicine 2013; 8: 428-435. (C) 2013 Society of Hospital Medicine C1 [Lindenauer, Peter K.] Baystate Med Ctr, Ctr Qual Care Res, Springfield, MA 01199 USA. [Lindenauer, Peter K.] Baystate Med Ctr, Div Gen Internal Med, Springfield, MA 01199 USA. [Lindenauer, Peter K.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Grosso, Laura M.; Wang, Changqin; Wang, Yun; Bernheim, Susannah M.; Drye, Elizabeth E.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Wang, Changqin; Wang, Yun] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Krishnan, Jerry A.] Univ Illinois, Sect Pulm Crit Care Sleep & Allergy, Chicago, IL USA. [Krishnan, Jerry A.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. [Lee, Todd A.] Univ Illinois, Dept Pharm Practice, Chicago, IL USA. [Lee, Todd A.] Univ Illinois, Dept Pharm Adm, Chicago, IL USA. [Au, David H.] VA Puget Sound HealthCare Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Mularski, Richard A.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. [Mularski, Richard A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bernheim, Susannah M.] Yale Univ, Sch Med, Dept Internal Med, Sect Gen Internal Med, New Haven, CT 06510 USA. [Drye, Elizabeth E.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. RP Lindenauer, PK (reprint author), Baystate Med Ctr, Ctr Qual Care Res, 759 Chestnut St, Springfield, MA 01199 USA. EM peter.lindenauer@bhs.org FU MIDS [HHSM-500-2008-0025I/HHSM-500-T0001]; NIH, Department of Veterans Affairs, AHRQ, and Gilead Sciences; CMS FX Peter K. Lindenauer, MD, MSc, is the guarantor of this article, taking responsibility for the integrity of the work as a whole, from inception to published article, and takes responsibility for the content of the manuscript, including the data and data analysis. All authors have made substantial contributions to the conception and design, or acquisition of data, or analysis and interpretation of data; have drafted the submitted article or revised it critically for important intellectual content; and have provided final approval of the version to be published. Preparation of this manuscript was completed under Contract Number: HHSM-500-2008-0025I/HHSM-500-T0001, Modification No. 000007, Option Year 2 Measure Instrument Development and Support (MIDS). Sponsors did not contribute to the development of the research or manuscript. Dr. Au reports being an unpaid research consultant for Bosch Inc. He receives research funding from the NIH, Department of Veterans Affairs, AHRQ, and Gilead Sciences. The views of the this manuscript represent the authors and do not necessarily represent those of the Department of Veterans Affairs. Drs. Drye and Bernheim report receiving contract funding from CMS to develop and maintain quality measures. NR 27 TC 4 Z9 4 U1 0 U2 3 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 AUG PY 2013 VL 8 IS 8 BP 428 EP 435 DI 10.1002/jhm.2066 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 196QU UT WOS:000322791400002 PM 23913593 ER PT J AU Burke, RE Donze, J Schnipper, JL AF Burke, Robert E. Donze, Jacques Schnipper, Jeffrey L. TI Contribution of psychiatric illness and substance abuse to 30-day readmission risk SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID HOSPITAL READMISSION; MENTAL-ILLNESS; CARE; DISORDERS; MORTALITY; LITERACY; QUALITY AB BACKGROUND: Little is known about the contribution of psychiatric illness to medical 30-day readmission risk. OBJECTIVE: To determine the independent contribution of psychiatric illness and substance abuse to all-cause and potentially avoidable 30-day readmissions in medical patients. DESIGN: Retrospective cohort study. SETTING: Patients discharged from the medicine services at a large teaching hospital from July 1, 2009 to June 30, 2010. MEASUREMENTS: The main outcome of interest was 30-day all-cause and potentially avoidable readmissions; the latter determined by a validated algorithm (SQLape) in both bivariate and multivariate analysis. Readmissions were captured at 3 hospitals where the majority of these patients are readmitted. RESULTS: Of 6987 discharged patients, 1260 were readmitted within 30 days (18.0%); 388 readmissions were potentially avoidable (5.6%). In multivariate analysis, 2 or more prescribed outpatient psychiatric medications (odds ratio [OR]: 1.1, 95% confidence interval [CI]: 1.01-1.20) or any prescription of anxiolytics (OR: 1.16, 95% CI: 1.001.35) were associated with increased all-cause readmissions, whereas discharge diagnoses of anxiety (OR: 0.82, 95% CI: 0.68-0.99) or substance abuse (OR: 0.80, 96% CI: 0.65-0.99) were associated with fewer all-cause readmissions. These findings were not replicated as predictors of potentially avoidable readmissions; rather, patients with discharge diagnoses of depression (OR: 1.49, 95% CI: 1.09-2.04) and schizophrenia (OR: 2.63, 95% CI: 1.13-6.13) were at highest risk. CONCLUSIONS: Our data suggest that patients treated during a hospitalization for depression and for schizophrenia are at higher risk for potentially avoidable 30-day readmissions, whereas those prescribed more psychiatric medications as outpatients are at increased risk for all-cause readmissions. These populations may represent fruitful targets for interventions to reduce readmission risk. (C) 2013 Society of Hospital Medicine C1 [Burke, Robert E.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs Med Ctr, Hosp Med Sect, Denver, CO USA. [Burke, Robert E.] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO USA. [Donze, Jacques; Schnipper, Jeffrey L.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Donze, Jacques; Schnipper, Jeffrey L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Schnipper, Jeffrey L.] Brigham & Womens Hosp BWH Hospitalist Serv, Boston, MA USA. RP Burke, RE (reprint author), Denver VA Med Ctr, Med Serv 111, 1055 Clermont St, Denver, CO 80220 USA. EM Robert.Burke5@va.gov FU Swiss National Science Foundation; Swiss Foundation for Medical-Biological Scholarships FX Dr. Donze was supported by the Swiss National Science Foundation and the Swiss Foundation for Medical-Biological Scholarships. The authors otherwise have no conflicts of interest to disclose. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Department of Veterans Affairs. NR 26 TC 11 Z9 11 U1 3 U2 5 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 AUG PY 2013 VL 8 IS 8 BP 450 EP 455 DI 10.1002/jhm.2044 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 196QU UT WOS:000322791400005 PM 23589474 ER PT J AU Khateeb, R Gandhi, T Dhaliwal, G AF Khateeb, Rafina Gandhi, Tejal Dhaliwal, Gurpreet TI A raw deal SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID Q-FEVER; INFECTIONS; CLUSTER C1 [Khateeb, Rafina] Univ Michigan Hlth Syst, Dept Internal Med, Div Gen Med, Ann Arbor, MI USA. [Gandhi, Tejal] Univ Michigan Hlth Syst, Dept Internal Med, Div Infect Dis, Ann Arbor, MI USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Med Serv, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Khateeb, R (reprint author), 3119 Taubman Ctr,1500 E Med Ctr Dr,SPC 5376, Ann Arbor, MI 48109 USA. EM rafina@umich.edu NR 9 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD AUG PY 2013 VL 8 IS 8 BP 464 EP 467 DI 10.1002/jhm.2055 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 196QU UT WOS:000322791400007 PM 23878111 ER PT J AU Wallace, GC Haar, CP Vandergrift, WA Giglio, P Dixon-Mah, YN Varma, AK Ray, SK Patel, SJ Banik, NL Das, A AF Wallace, Gerald C. Haar, Catherine P. Vandergrift, W. Alex, III Giglio, Pierre Dixon-Mah, Yaenette N. Varma, Abhay K. Ray, Swapan K. Patel, Sunil J. Banik, Naren L. Das, Arabinda TI Multi-targeted DATS prevents tumor progression and promotes apoptosis in ectopic glioblastoma xenografts in SCID mice via HDAC inhibition SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Diallyl trisulfide; p53; Mitosis; Histone deacetylase ID PROSTATE-CANCER CELLS; MOLECULAR-MECHANISMS; GARLIC COMPOUNDS; IN-VIVO; HISTONE ACETYLATION; DIALLYL DISULFIDE; INDUCTION; NEUROBLASTOMA; LIVER; MODEL AB Glioblastoma, the most lethal brain tumor, remains incurable despite aggressive chemotherapy and surgical interventions. New chemotherapeutics for glioblastoma have been explored in preclinical models and some agents have reached the clinical setting. However, success rates are not significant. Previous investigations involving diallyl trisulfide (DATS), a garlic compound, indicated significant anti-cancer effects in glioblastoma in vitro. DATS has also been shown to inhibit histone deacetylase activity and impede glioblastoma tumor progression. We hypothesized that DATS would block ectopic U87MG tumor by multiple pro-apoptotic pathways via inhibiting histone deacetylase (HDAC). To prove this, we developed ectopic U87MG tumors in SCID mice and treated them daily with intraperitoneal injections of DATS for 7 days. Results indicated that DATS (10 mu g/kg-10 mg/kg) dose-dependently reduced tumor mass and number of mitotic cells within tumors. Histological and biochemical assays demonstrated that DATS reduced mitosis in tumors, decreased HDAC activity, increased acetylation of H3 and H4, inhibited cell cycle progression, decreased pro-tumor markers (e.g., survivin, Bcl-2, c-Myc, mTOR, EGFR, VEGF), promoted apoptotic factors (e.g., bax, mcalpian, active caspase-3), and induced DNA fragmentation. Our data also demonstrated an increase in p21Waf1 expression, which correlated with increased p53 expression and MDM2 degradation following DATS treatment. Finally, histological assessment and enzyme assays showed that even the highest dose of DATS did not negatively impact hepatic function. Collectively, our results clearly demonstrated that DATS could be an effective therapeutic agent in preventing tumor progression and inducing apoptosis in human glioblastoma in vivo, without impairing hepatic function. C1 [Wallace, Gerald C.; Haar, Catherine P.; Vandergrift, W. Alex, III; Giglio, Pierre; Dixon-Mah, Yaenette N.; Varma, Abhay K.; Patel, Sunil J.; Banik, Naren L.; Das, Arabinda] Med Univ S Carolina, Dept Neurosci Neurol & Neurooncol, Charleston, SC 29425 USA. [Wallace, Gerald C.; Haar, Catherine P.; Vandergrift, W. Alex, III; Giglio, Pierre; Dixon-Mah, Yaenette N.; Varma, Abhay K.; Patel, Sunil J.; Banik, Naren L.; Das, Arabinda] Med Univ S Carolina, MUSC Brain & Spine Tumor Program, Charleston, SC 29425 USA. [Ray, Swapan K.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC USA. [Banik, Naren L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Das, A (reprint author), Med Univ S Carolina, Dept Neurosci Neurol & Neurooncol, Charleston, SC 29425 USA. EM dasa@musc.edu FU Veteran Administration Research Program [NS-38146, NS-41088, 101BX001262]; Jerry Zucker Fund for Brain Tumor Research at the MUSC Foundation; [SC SCIRF-11-002] FX Completion of this investigation was made possible in part by these Grants (NS-38146, NS-41088, 101BX001262 [Veteran Administration Research Program], and SC SCIRF-11-002) and Jerry Zucker Fund for Brain Tumor Research at the MUSC Foundation. NR 28 TC 13 Z9 13 U1 2 U2 17 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 AUG PY 2013 VL 114 IS 1 BP 43 EP 50 DI 10.1007/s11060-013-1165-8 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 191EH UT WOS:000322395200005 PM 23754639 ER PT J AU Jiang, XY Reardon, DA Desjardins, A Vredenburgh, JJ Quinn, JA Austin, AD Herndon, J McLendon, RE Friedman, HS AF Jiang, Xiaoyin Reardon, David A. Desjardins, Annick Vredenburgh, James J. Quinn, Jennifer A. Austin, Alan D. Herndon, James E., II McLendon, Roger E. Friedman, Henry S. TI O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Temozolomide; MGMT; Primary central nervous system lymphoma; Chemotherapy; Immunohistochemistry ID NERVOUS-SYSTEM LYMPHOMA; B-CELL LYMPHOMA; PROTEIN EXPRESSION; COMPLETE RESPONSE; SALVAGE TREATMENT; GLIOBLASTOMA; CHEMOTHERAPY; METHOTREXATE; METHYLATION; RITUXIMAB AB Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O-6-methylguanine-DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized that MGMT immunohistochemistry would predict resistance to temozolomide in PCNSL. A retrospective study of newly-diagnosed and recurrent PCNSL patients treated at our institution was conducted to study the predictive value of MGMT immunohistochemistry for response to temozolomide. 20 patients who were treated with temozolomide as a single agent were identified during the study time period. 6/20 patients demonstrated a response, corresponding to an objective response rate of 30 % (95 % CI 8-52). Five patients with low MGMT level (< 30 %) showed a response to temozolomide. Only one of 10 patients (10 %) with high MGMT level (a parts per thousand yen30 %) exhibited a response to temozolomide. Small sample numbers precluded formal statistical comparisons. Two patients with complete response remain alive without progressive disease 6.7 and 7.2 years after temozolomide initiation. Immunohistochemistry can be performed on small biopsies to selectively assess MGMT status in tumor versus surrounding inflammation. MGMT analysis by immunohistochemistry may predict response to temozolomide in PCNSL and should be prospectively investigated. C1 [Jiang, Xiaoyin; Austin, Alan D.; McLendon, Roger E.] Duke Univ, Dept Pathol, Med Ctr, Durham, NC 27710 USA. [Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Desjardins, Annick; Herndon, James E., II; Friedman, Henry S.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [Vredenburgh, James J.] St Francis Hosp & Med Ctr, Hartford, CT 06105 USA. [Quinn, Jennifer A.] UNC Hosp, Chapel Hill, NC 27514 USA. RP Jiang, XY (reprint author), Duke Univ, Dept Pathol, Med Ctr, Box 3712 DUMC, Durham, NC 27710 USA. EM jiang009@mc.duke.edu OI Jiang, Xiaoyin/0000-0002-3069-3130 NR 34 TC 5 Z9 6 U1 0 U2 5 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 AUG PY 2013 VL 114 IS 1 BP 135 EP 140 DI 10.1007/s11060-013-1162-y PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 191EH UT WOS:000322395200016 PM 23686298 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Suite 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 0 Z9 0 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2013 VL 110 IS 3 BP 573 EP 574 DI 10.1152/jn.00338.2013 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 195PJ UT WOS:000322715500001 PM 23678018 ER PT J AU Furman, AC Kujawa, SG Liberman, MC AF Furman, Adam C. Kujawa, Sharon G. Liberman, M. Charles TI Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE excitotoxicity; noise-induced hearing loss; auditory nerve ID AUDITORY-NERVE FIBERS; GUINEA-PIG; CHARACTERISTIC FREQUENCY; HEARING-LOSS; CAT COCHLEA; CELL LOSS; AFFERENT; INNERVATION; SYNAPSES; MICE AB Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system. C1 [Kujawa, Sharon G.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Furman, Adam C.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Furman, Adam C.; Kujawa, Sharon G.; Liberman, M. Charles] Harvard Program Speech & Hearing Biosci & Technol, Boston, MA USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Charles_Liberman@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders [RO1 DC-00188, P30 DC-05029, R01 DC-08577, T32 DC-00038] FX This work was supported by research, core, and training grants from National Institute on Deafness and Other Communication Disorders RO1 DC-00188 (M. C. Liberman), P30 DC-05029 (M. C. Liberman), R01 DC-08577 (S. G. Kujawa), and T32 DC-00038 (A. C. Furman). NR 38 TC 130 Z9 132 U1 5 U2 42 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2013 VL 110 IS 3 BP 577 EP 586 DI 10.1152/jn.00164.2013 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 195PJ UT WOS:000322715500003 PM 23596328 ER PT J AU Costine, BA Saliga, K Seufert, C Fiorello, M Killbaugh, TJ Margulies, S Duhaime, AC AF Costine, Beth A. Saliga, Kristen Seufert, Christopher Fiorello, Marissa Killbaugh, Todd J. Margulies, Susan Duhaime, Ann-Christine TI TARGETING MITOCHONDRIA WITH CYCLOSPORIN A AFTER CORTICAL IMPACT IN AN IMMATURE LARGE ANIMAL MODEL SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 31st Annual National Neurotrauma Symposium CY AUG 04-07, 2013 CL Nashville, TN DE cyclosporin A; mitochondria; pediatric; translational C1 [Costine, Beth A.; Saliga, Kristen; Duhaime, Ann-Christine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Seufert, Christopher] Tufts Univ, Sch Med, Medford, MA 02155 USA. [Killbaugh, Todd J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Margulies, Susan] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2013 VL 30 IS 15 BP A157 EP A158 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 191WY UT WOS:000322446800298 ER PT J AU Killbaugh, TJ Costine, BA Saliga, K Byro, M Bebee, A Weeks, D Sullivan, S Ralston, J Friess, S Zuppa, A Robertson, C Propert, K Smith, C Duhaime, AC Margulies, S AF Killbaugh, Todd J. Costine, Beth A. Saliga, Kristen Byro, Melissa Bebee, Ashley Weeks, Dianna Sullivan, Sarah Ralston, Jill Friess, Stuart Zuppa, Athena Robertson, Courtney Propert, Kathleen Smith, Colin Duhaime, Ann-Christine Margulies, Susan TI IMMATURE LARGE ANIMAL TRANSLATIONAL TREATMENT TRIAL WITH MITOCHONDRIAL TARGETED PHARMACOLOGIC INTERVENTION FOR TRAUMATIC BRAIN INJURY IN CHILDREN SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 31st Annual National Neurotrauma Symposium CY AUG 04-07, 2013 CL Nashville, TN DE Cyclosporin A; mitochondria; pediatric; TBI; translational C1 [Killbaugh, Todd J.; Byro, Melissa; Bebee, Ashley; Weeks, Dianna; Sullivan, Sarah; Ralston, Jill; Zuppa, Athena; Propert, Kathleen; Margulies, Susan] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Costine, Beth A.; Saliga, Kristen; Duhaime, Ann-Christine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Friess, Stuart] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Smith, Colin] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2013 VL 30 IS 15 BP A15 EP A16 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 191WY UT WOS:000322446800025 ER PT J AU Margulies, S Killbaugh, TJ Sullivan, S Costine, BA Janesko-Feldman, K Berger, R Duhaime, AC AF Margulies, Susan Killbaugh, Todd J. Sullivan, Sarah Costine, Beth A. Janesko-Feldman, Keri Berger, Rachel Duhaime, Ann-Christine TI TIME-DEPENDENT CHANGES IN BIOMARKER LEVELS FOLLOWING BOTH DIFFUSE AND FOCAL TBI IN IMMATURE SWINE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 31st Annual National Neurotrauma Symposium CY AUG 04-07, 2013 CL Nashville, TN DE NSE; pediatric; porcine; S100B; TBI C1 [Margulies, Susan; Killbaugh, Todd J.; Sullivan, Sarah] Univ Penn, Philadelphia, PA 19104 USA. [Costine, Beth A.; Duhaime, Ann-Christine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Janesko-Feldman, Keri] Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. [Berger, Rachel] Childrens Hosp Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2013 VL 30 IS 15 BP A67 EP A68 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 191WY UT WOS:000322446800124 ER PT J AU Miller, RS Brenner, L Churchill, S Bahraini, N Price, R Skiba, V Caviness, J Mooney, S Weaver, L AF Miller, R. Scott Brenner, Lisa Churchill, Susan Bahraini, Nazanin Price, Robert Skiba, Virginia Caviness, James Mooney, Scott Weaver, Lindell TI A PHASE II, RANDOMIZED, SHAM-CONTROLLED TRIAL HYPERBARIC OXYGEN FOR POST-CONCUSSION SYNDROME: IMPACT OF INTERVENTION ON SYMPTOMS AND WELL BEING SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 31st Annual National Neurotrauma Symposium CY AUG 04-07, 2013 CL Nashville, TN DE hyperbaric oxygen; post-concussion syndrome; sham-controlled randomized trial C1 [Miller, R. Scott] US Army Med Mat Dev Act, Ft Carson, CO USA. [Brenner, Lisa; Bahraini, Nazanin] Denver VA Med Ctr, Ft Carson, CO USA. [Churchill, Susan; Weaver, Lindell] LDS Hosp, Ft Carson, CO USA. [Price, Robert] Evans Army Community Hosp, Ft Carson, CO USA. [Mooney, Scott] Eisenhower Army Med Ctr, Ft Gordon, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG PY 2013 VL 30 IS 15 BP A56 EP A56 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 191WY UT WOS:000322446800103 ER PT J AU Ritchie, CS Zulman, DM AF Ritchie, Christine S. Zulman, Donna M. TI Research Priorities in Geriatric Palliative Care: Multimorbidity SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID MULTIPLE CHRONIC CONDITIONS; RANDOMIZED CONTROLLED-TRIALS; CHRONIC HEART-FAILURE; QUALITY-OF-LIFE; PATIENT COMPLEXITY; CHRONIC DISEASES; DIABETES CARE; COMORBIDITY; IMPACT; HEALTH AB With global aging and scientific advances extending survival, the number of adults experiencing multiple chronic conditions has grown substantially and is projected to increase by another third between 2000 and 2030. Among the many challenges posed by multimorbidity, some of the most pressing include how to characterize and measure comorbid conditions, understand symptoms and illness burden, and provide person-centered care in the context of competing health care priorities and increasing complexity. In this white paper emanating from a National Institute on Aging supported conference to discuss research gaps at the geriatrics-palliative care interface, the authors review common definitions of multimorbidity; describe the association between multimorbidity and quality of life, functional status, quality of care, and health care utilization; note content and methodological gaps in multimorbidity evidence; and make recommendations regarding research priorities in this area of expanding public health impact. C1 [Ritchie, Christine S.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Ritchie, Christine S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ritchie, Christine S.] Jewish Home San Francisco, San Francisco, CA USA. [Zulman, Donna M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Zulman, Donna M.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Palo Alto, CA USA. RP Ritchie, CS (reprint author), Univ Calif San Francisco, Sch Med, 3333 Calif St,Suite 380, San Francisco, CA 94143 USA. EM christine.ritchie@ucsf.edu FU National Institute on Aging Claude D. Pepper Older Americans Independence Center at the Icahn School of Medicine at Mount Sinai [5P30AG028741]; Advanced Illness and Multimorbidity Geriatric Academic Leadership Award [K07AG31779]; National Institute for Nursing Research; Commonwealth Fund; Retirement Research Foundation; Stephen D. Bechtel Foundation through the Program for the Aging Century; career development award through Veterans Affairs Health Services Research Development [CDA 12-173] FX This work was supported by the National Institute on Aging Claude D. Pepper Older Americans Independence Center at the Icahn School of Medicine at Mount Sinai (5P30AG028741). Dr. Ritchie is supported by the Advanced Illness and Multimorbidity Geriatric Academic Leadership Award (K07AG31779); and by the National Institute for Nursing Research, the Commonwealth Fund, the Retirement Research Foundation, and the Stephen D. Bechtel Foundation through the Program for the Aging Century. Dr. Zulman is supported by a career development award through Veterans Affairs Health Services Research & Development (CDA 12-173). NR 44 TC 4 Z9 4 U1 6 U2 20 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2013 VL 16 IS 8 BP 843 EP 847 DI 10.1089/jpm.2013.9491 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 187JT UT WOS:000322114600012 PM 23777331 ER PT J AU Jackson, VA Jacobsen, J Greer, JA Pirl, WF Temel, JS Back, AL AF Jackson, Vicki A. Jacobsen, Juliet Greer, Joseph A. Pirl, William F. Temel, Jennifer S. Back, Anthony L. TI The Cultivation of Prognostic Awareness Through the Provision of Early Palliative Care in the Ambulatory Setting: A Communication Guide SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID DISCUSSING PROGNOSIS; CANCER-PATIENTS; TERMINAL ILLNESS; INFORMATION; PATIENT; TALKING; WANT; HOPE AB Early, integrated palliative care delivered in the ambulatory setting has been associated with improved quality of life, lower rates of depression, and even prolonged survival. We outline an expert practice that provides a step-wise approach to cultivating prognostic awareness in patients cared for by a palliative care clinician early in the course of the patient's disease. This approach can be used by both novice and more experienced palliative care clinicians. C1 [Jackson, Vicki A.; Jacobsen, Juliet] Massachusetts Gen Hosp, Div Palliat Care, Boston, MA 02114 USA. [Jacobsen, Juliet] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Greer, Joseph A.; Pirl, William F.; Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Back, Anthony L.] Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. RP Jackson, VA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Palliat Care, Founders 600,55 Fruit St, Boston, MA 02114 USA. EM vjackson@partners.org NR 20 TC 30 Z9 30 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2013 VL 16 IS 8 BP 894 EP 900 DI 10.1089/jpm.2012.0547 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 187JT UT WOS:000322114600019 PM 23786425 ER PT J AU Harte, CB AF Harte, Christopher B. TI The Relationship between Resting Heart Rate Variability and Erectile Tumescence among Men with Normal Erectile Function SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Heart Rate Variability; Cardiac Autonomic Function; Sexual Arousal; Erectile Tumescence; Erectile Function; Erectile Physiology ID PENILE-VAGINAL INTERCOURSE; INTERNATIONAL INDEX; AUTONOMIC FUNCTION; BLOOD-PRESSURE; FUNCTION IIEF; DYSFUNCTION; FREQUENCY; PATHOPHYSIOLOGY; PHYSIOLOGY; MORTALITY AB Introduction. Individuals with erectile dysfunction (ED) have been shown to display lower heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. No studies have explored whether HRV is predictive of erectile response among men with clinically normal erectile function. Aim. The study aims to examine associations between resting HRV and objective measures of genital response (i.e., resting penile circumference; erectile tumescence) and self-reported sexual function. Methods. The sample comprised 59 male community volunteers (mean age = 20.15 years; SD = 2.52) selected from the control conditions of two previously published studies. Participants reported erectile function in the normal range (scoring >= 26 on the International Index of Erectile Function [IIEF]) and had no history of cardiovascular disease or myocardial infarct. During a laboratory visit, self-report, anthropometric, cardiovascular, and electrocardiographic data were assessed, as well as resting penile circumference and erectile tumescence in response to viewing an erotic film. Main Outcome Measures. Resting penile responses, erectile tumescence (circumferential change via penile plethysmography), self-reported sexual function per the IIEF, and both time-domain (standard deviation of beat-to-beat [NN] intervals, square root of the mean squared difference of successive NN intervals, and percent of NN intervals for which successive heartbeat intervals differed by at least 50 msec [pNN50]) and frequency-domain (low frequency [LF], high frequency [HF], LF/HF ratio) parameters of HRV were assessed. Results. Higher-resting HF power and lower-resting LF/HF ratio were associated with greater erectile tumescence. There were marginally significant positive associations between mean NN interval and pNN50 and penile tumescence. HRV was not associated with self-reported sexual function or with resting penile circumference. Conclusions. Results suggested that, among men without ED, relatively elevated parasympathetic tone was predictive of larger erectile tumescence. Limited variance in sexual function scores may have accounted for the lack of association between HRV and IIEF scores. C1 [Harte, Christopher B.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Harte, Christopher B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Harte, CB (reprint author), VA Boston Healthcare Syst, Res Serv, 150 S Huntington Ave 116-B4, Boston, MA 02130 USA. EM christopher.harte@va.gov OI Harte, Christopher/0000-0002-8097-7369 FU National Institute of Child Health and Human Development (NICHD) [1 RO1 HD051676-01 A1] FX Portions of this work were made possible by Grant Number 1 RO1 HD051676-01 A1 to Cindy Meston from the National Institute of Child Health and Human Development (NICHD). The contents are solely the responsibility of the author and do not necessarily represent the official views of the NICHD. NR 37 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD AUG PY 2013 VL 10 IS 8 BP 1961 EP 1968 DI 10.1111/jsm.12197 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 193TW UT WOS:000322585400009 PM 23802770 ER PT J AU Bober, SL Zhou, ES Chen, B Manley, PE Kenney, LB Recklitis, CJ AF Bober, Sharon L. Zhou, Eric S. Chen, Bing Manley, Peter E. Kenney, Lisa B. Recklitis, Christopher J. TI Sexual Function in Childhood Cancer Survivors: A Report from Project REACH SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Cancer Survivorship; Young Adult; Psycho-Sexual; Pediatric Cancer ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; BRIEF SYMPTOM INVENTORY-18; YOUNG-ADULT SURVIVORS; BREAST-CANCER; UNITED-STATES; OUTCOMES; HEALTH; PREDICTORS; FERTILITY AB Introduction. Of the approximately 12,000 children and adolescents that will be diagnosed with cancer in 2013, it is expected that over 80% of them will become long-term adult survivors of childhood cancer. Although it has been well established that cancer treatment often has profound negative impact on sexual functioning, sexual functioning in adult survivors of childhood cancer is not well understood. Aim. The aim of the current study was to examine the report of sexual function in adult survivors of childhood cancer in relationship to both physical and emotional functioning. Methods. Two hundred ninety-one participants enrolled in Project REACH, a longitudinal study of childhood cancer survivors, completed questionnaires as part of an annual health survey. Main Outcome Measure. Primary outcome measures included the sexual functioning subscale of the Swedish Health-Related Quality of Life Survey, the SF-12, and the BSI-18. Results. Results indicate that 29% of young adult survivors reported two or more discrete symptoms of sexual dysfunction. Females were twice as likely to report sexual problems. Sexual problems were not related to specific types of childhood cancer treatments such as type of chemotherapy or radiation. Young adults with sexual dysfunction did report poorer functioning across the range of SF-12 subscales including physical functioning, general health, fatigue, and mental health. Conclusions. Significant sexual dysfunction is common in adult survivors of childhood cancer. A greater understanding of the particular relationship between sexual dysfunction and both physical and emotional well-being in this relatively young population is needed. Even when long-term cancer survivors are young adults and report generally good health, results underscore the need for clinicians to specifically assess sexual functioning. C1 [Bober, Sharon L.; Zhou, Eric S.; Chen, Bing; Kenney, Lisa B.; Recklitis, Christopher J.] Brigham & Womens Hosp, Dana Farber Canc Inst, David B Perini Qual Life Clin, Boston, MA 02115 USA. [Bober, Sharon L.; Zhou, Eric S.; Chen, Bing; Manley, Peter E.; Kenney, Lisa B.; Recklitis, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Manley, Peter E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Pediat Neurooncol Outcomes Clin, Boston, MA 02115 USA. RP Bober, SL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, David B Perini Qual Life Clin, 44 Binney St,D321, Boston, MA 02115 USA. EM sharon_bober@dfci.harvard.edu NR 48 TC 21 Z9 21 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD AUG PY 2013 VL 10 IS 8 BP 2084 EP 2093 DI 10.1111/jsm.12193 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 193TW UT WOS:000322585400022 PM 23679087 ER PT J AU Foering, K Chang, AY Piette, EW Cucchiara, A Okawa, J Werth, VP AF Foering, Kristen Chang, Aileen Y. Piette, Evan W. Cucchiara, Andrew Okawa, Joyce Werth, Victoria P. TI Characterization of clinical photosensitivity in cutaneous lupus erythematosus SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Dermatology Research agenda conference CY JUN 22-23, 2012 CL Washington, DC DE cutaneous lupus erythematosus; dendritic cells; immunohistochemistry; photosensitivity; polymorphic light eruption; systemic lupus erythematosus ID POLYMORPHOUS LIGHT ERUPTION; QUALITY-OF-LIFE; TERM-FOLLOW-UP; DISEASE-ACTIVITY; SEVERITY INDEX; T-CELLS; SKIN; MANIFESTATIONS; RESIDENT; LESIONS AB Background: Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. Objective: We sought to characterize self-reported PS in cutaneous LE (CLE). Methods: The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. Results: In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). Limitations: PS was inferred from patient report and not directly observed. Conclusions: Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology. C1 [Foering, Kristen; Chang, Aileen Y.; Piette, Evan W.; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Vet Affairs Med Ctr, Philadelphia Dept, Philadelphia, PA 19104 USA. [Foering, Kristen; Chang, Aileen Y.; Piette, Evan W.; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Foering, Kristen; Cucchiara, Andrew] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, PCAM Suite 1-330S,3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU National Institutes of Health [NIH K24-AR 18 02207]; National Center for Advancing Translational Research [TL1RR024133]; National Center for Advancing Translational Science [TL1TR00138]; Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This material is based upon work supported by the National Institutes of Health, including NIH K24-AR 18 02207 (Dr Werth); National Center for Advancing Translational Research TL1RR024133, which is now National Center for Advancing Translational Science TL1TR00138 (Drs Foering and Cucchiara); and Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 31 TC 10 Z9 10 U1 1 U2 4 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 AUG PY 2013 VL 69 IS 2 BP 205 EP 213 DI 10.1016/j.jaad.2013.03.015 PG 9 WC Dermatology SC Dermatology GA 186TK UT WOS:000322068100027 PM 23648190 ER PT J AU Amick, MM Clark, A Fortier, CB Esterman, M Rasmusson, AM Kenna, A Milberg, WP McGlinchey, R AF Amick, Melissa M. Clark, Alexandra Fortier, Catherine B. Esterman, Michael Rasmusson, Ann M. Kenna, Alexandra Milberg, William P. McGlinchey, Regina TI PTSD Modifies Performance on a Task of Affective Executive Control among Deployed OEF/OIF Veterans with Mild Traumatic Brain Injury SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Post-traumatic stress disorder; Attention; Brain injury; Military; Cognition; Deployment ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY PERSONNEL; LARGE-SAMPLE; HEAD-INJURY; IRAQ-WAR; ATTENTION; INFORMATION; AFGHANISTAN; INHIBITION; VOLUNTEERS AB Individuals with post-traumatic stress disorder (PTSD) show a cognitive bias for threatening information, reflecting dysregulated executive control for affective stimuli. This study examined whether comorbid mild Traumatic Brain Injury (mTBI) with PTSD exacerbates this bias. A computer-administered Affective Go/No-Go task measured reaction times (RTs) and errors of omission and commission to words with a non-combat-related positive or negative valence in 72 deployed United States service members from the wars in Iraq and Afghanistan. Incidents of military-related mTBI were measured with the Boston Assessment of Traumatic Brain Injury-Lifetime. PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Participants were divided into those with (mTBI+, n = 34) and without a history of military-related mTBI (mTBI-, n = 38). Valence of the target stimuli differentially impacted errors of commission and decision bias (criterion) in the mTBI+ and mTBI- groups. Specifically, within the mTBI+ group, increasing severity of PTSD symptoms was associated with an increasingly liberal response pattern (defined as more commission errors to negative distractors and greater hit rate for positive stimuli) in the positive compared to the negative blocks. This association was not observed in the mTBI- group. This study underscores the importance of considering the impact of a military-related mTBI and PTSD severity upon affective executive control. C1 [Amick, Melissa M.; Clark, Alexandra; Fortier, Catherine B.; Esterman, Michael; Rasmusson, Ann M.; Kenna, Alexandra; Milberg, William P.; McGlinchey, Regina] VA Boston Healthcare Syst, Translat Res Ctr Traumat Brain Injury & Stress Di, Boston, MA 02130 USA. [Amick, Melissa M.; Esterman, Michael; Rasmusson, Ann M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Fortier, Catherine B.; Milberg, William P.; McGlinchey, Regina] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Milberg, William P.; McGlinchey, Regina] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. RP Amick, MM (reprint author), VA Boston Healthcare Syst 182 JP, Translat Res Ctr Traumat Brain Injury & Stress Di, 150 South Huntington Ave, Boston, MA 02130 USA. EM melissa.amick@va.gov OI Esterman, Michael/0000-0002-9000-3920 FU RR&D TBI Center of Excellence at VA Boston Healthcare System, The Translational Research Center for TBI and Stress Disorders; VA Rehabilitation Research and Development Center [B6796-C] FX This work was supported by the RR&D TBI Center of Excellence at VA Boston Healthcare System, The Translational Research Center for TBI and Stress Disorders. We thank all of the individuals who participated in this study. We thank Dr. Gheorghe Doros for his advisement in our statistical approach. We are grateful to all members of the Human Characterization Core of TRACTS: Marge Alhquist, BS, Brad Brummett, PhD, Racheal Dayton, BS, Andrea Levine, MA, Kathleen Moriarty, BS, Lindsay Morra, BA, Roxanne Moyer, BS, Erica Scioli, PhD, Jonathan Venne, BS, Ruby Ward, BA, David Zade PhD for their expert assessment skills. We would also like to thank Walter Musto for his extraordinary recruitment efforts and Joe Degutis, PhD, Jennifer Vasterling, PhD, and Mieke Verfaellie PhD, for valuable feedback in the interpretation of our results. These findings were presented in part at the annual meetings of the International Neuropsychological Society, 2011, the International Trauma and Stress Society, 2011, the Federal Interagency Conference on TBI, 2011, and the American Psychological Association, 2012. The authors report no conflicts of interest. This research was supported by a VA Rehabilitation Research and Development Center Grant B6796-C awarded to Dr. Regina McGlinchey. NR 58 TC 7 Z9 8 U1 3 U2 20 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 AUG PY 2013 VL 19 IS 7 BP 792 EP 801 DI 10.1017/S1355617713000544 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 186CI UT WOS:000322018900006 PM 23823533 ER PT J AU Esterman, M DeGutis, J Mercado, R Rosenblatt, A Vasterling, JJ Milberg, W McGlinchey, R AF Esterman, Michael DeGutis, Joseph Mercado, Rogelio Rosenblatt, Andrew Vasterling, Jennifer J. Milberg, William McGlinchey, Regina TI Stress-Related Psychological Symptoms Are Associated with Increased Attentional Capture by Visually Salient Distractors SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Attention; PTSD; Executive function; Reaction time; Depression; Concentration ID DISORDER; PTSD; DYSFUNCTION; DEPRESSION; SURVIVORS; NETWORKS; ANXIETY; NOVELTY; TRAUMA AB Research has shown that attention can be abnormally drawn to salient threat-or trauma-related information in individuals with posttraumatic stress and related psychological symptoms. The nature of this attentional bias is thought to derive from capture of attention toward potential threat overpowering the volitional, goal-directed attentional system. However, it is unclear whether this pattern of attentional dysregulation generalizes to salient, but non-emotional types of information. Using a well-established and sensitive measure of attentional capture, the current study demonstrates that posttraumatic psychological symptom severity is associated with the capture of attention by visually salient, non-emotional distractors. Specifically, during visual search for a unique shape, the presence of a task-irrelevant but salient color singleton disrupted search efficiency, and this disruption was correlated with both posttraumatic stress disorder (PTSD) and depression symptom severity as assessed by self-report. These findings suggest that posttraumatic stress and depression may be characterized as involving a general alteration of the balance between salience-based and goal-directed attentional systems. C1 [Esterman, Michael; DeGutis, Joseph; Mercado, Rogelio; Rosenblatt, Andrew; Vasterling, Jennifer J.; Milberg, William; McGlinchey, Regina] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Esterman, Michael; Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [DeGutis, Joseph; Milberg, William; McGlinchey, Regina] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Esterman, M (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 182 JP, Boston, MA 02130 USA. EM esterman@bu.edu OI Esterman, Michael/0000-0002-9000-3920 FU VA Rehabilitation Research and Development Career Development Award; Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C] FX We thank Jeff Moher for the use of his task, as well as Monica Rosenberg and Sarah Noonan for their fruitful discussions. The present work is supported by a VA Rehabilitation Research and Development Career Development Award (to J.D.) as well as by the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C). Authors have no financial or other relationships that could be interpreted as a conflict of interest affecting this manuscript. NR 29 TC 12 Z9 12 U1 2 U2 18 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 AUG PY 2013 VL 19 IS 7 BP 835 EP 840 DI 10.1017/S135561771300057X PG 6 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 186CI UT WOS:000322018900011 PM 23803518 ER PT J AU Bateman, BT Rassen, JA Schneeweiss, S Bykov, K Franklin, JM Gagne, JJ Polinski, JM Liu, J Kulik, A Fischer, MA Choudhry, NK AF Bateman, Brian T. Rassen, Jeremy A. Schneeweiss, Sebastian Bykov, Katsiaryna Franklin, Jessica Myers Gagne, Joshua J. Polinski, Jennifer M. Liu, Jun Kulik, Alexander Fischer, Michael A. Choudhry, Niteesh K. TI Adjuvant vancomycin for antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MAJOR NONCARDIAC SURGERY; CARDIAC-SURGERY; ADMINISTRATIVE DATA; MORTALITY; DIARRHEA; DISEASE; EPIDEMIOLOGY; OPERATIONS; CEFAZOLIN; THERAPY AB Objective: The incidence of hospital-acquired Clostridium difficile infection (CDI) has increased rapidly over the past decade; patients undergoing major surgery, including coronary artery bypass grafting (CABG), are at particular risk. Intravenous vancomycin exposure has been identified as an independent risk factor for CDI, but this is controversial. It is not known whether vancomycin administered for surgical site infection prophylaxis increases the risk of CDI. Methods: Using data from the Premier Perspective Comparative Database, we assembled a cohort of 69,807 patients undergoing CABG surgery between 2004 and 2010 who received either a cephalosporin alone (65.1%) or a cephalosporin plus vancomycin (34.9%) on the day of surgery. Patients were observed for CDI until discharge from the index hospitalization. In these groups, we evaluated the comparative rate of postoperative CDI with Cox models; confounding was addressed using propensity scores. Results: In all, 77 (0.32%) of the 24,393 patients receiving a cephalosporin plus vancomycin and 179 (0.39%) of the 45,414 patients receiving a cephalosporin alone had postoperative CDI (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.95). After adjusting for confounding variables with either propensity score matching or stratification, there was no meaningful association between adjuvant vancomycin exposure and postoperative CDI (HR, 0.85; 95% CI, 0.61-1.19; and HR, 0.85; 95% CI, 0.63-1.15, respectively). Results of multiple sensitivity analyses were similar to the main findings. Conclusions: After adjustment for patient and surgical characteristics, a short course of prophylactic vancomycin was not associated with an increased risk of CDI among patients undergoing CABG surgery. C1 [Bateman, Brian T.; Rassen, Jeremy A.; Schneeweiss, Sebastian; Bykov, Katsiaryna; Franklin, Jessica Myers; Gagne, Joshua J.; Polinski, Jennifer M.; Liu, Jun; Fischer, Michael A.; Choudhry, Niteesh K.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Rassen, Jeremy A.; Schneeweiss, Sebastian; Bykov, Katsiaryna; Franklin, Jessica Myers; Gagne, Joshua J.; Polinski, Jennifer M.; Liu, Jun; Fischer, Michael A.; Choudhry, Niteesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kulik, Alexander] Florida Atlantic Univ, Boca Raton Reg Hosp, Lynn Heart & Vasc Inst, Boca Raton, FL 33431 USA. [Kulik, Alexander] Florida Atlantic Univ, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Med, Dept Anesthesia Crit Care & Pain Med,Div Pharmaco, 75 Francis St, Boston, MA 02115 USA. EM BBateman@partners.org RI Schneeweiss, Sebastian/C-2125-2013 FU National Institutes of Health [GM007592]; AHRQ; Food and Drug Administration; WHISCON LLC; Booz Co FX Supported by National Institutes of Health grant GM007592 (Dr Bateman). Dr Schneeweiss is Principal Investigator of the Brigham and Women's Hospital DEcIDE Center on Comparative Effectiveness Research and the DEcIDE Methods Center, both funded by AHRQ and of the Harvard-Brigham Drug Safety and Risk Management Research Center funded by Food and Drug Administration. Dr Schneeweiss is a paid consultant to WHISCON LLC and Booz & Co, and he is principal investigator of investigator-initiated grants to the Brigham and Women's Hospital from Pfizer, Novartis, and Boehringer-Ingelheim unrelated to the topic of this study. NR 31 TC 7 Z9 8 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 AUG PY 2013 VL 146 IS 2 BP 472 EP 478 DI 10.1016/j.jtcvs.2013.02.075 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 194LS UT WOS:000322635400035 PM 23541855 ER PT J AU Lancaster, RT Conrad, MF Patel, VI Cambria, MR Ergul, EA Cambria, RP AF Lancaster, Robert T. Conrad, Mark F. Patel, Virendra I. Cambria, Matthew R. Ergul, Emel A. Cambria, Richard P. TI Further experience with distal aortic perfusion and motor-evoked potential monitoring in the management of extent I-III thoracoabdominal aortic anuerysms SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 21-23, 2012 CL Boston, MA SP New England Soc Vasc Surg ID CEREBROSPINAL-FLUID DRAINAGE; COLLATERAL NETWORK CONCEPT; ANEURYSM REPAIR; SPINAL-CORD; CIRCULATORY ARREST; NEUROLOGIC DEFICIT; CLINICAL-TRIAL; PARAPLEGIA; OUTCOMES; RISK AB Background: Prior studies indicated improved early mortality and paraplegia rates in a small cohort of patients with type I-III thoracoabdominal aortic aneurysms (TAAs) treated with atriofemoral bypass (AFB) and motor-evoked potentials (MEVPs) when compared with a propensity-matched cohort of patients treated with the clamp and sew (CS) method, wherein epidural cooling was the principal spinal cord protective adjunct. The use of AFB/MEVP increases the complexity of TAA repair and in this study, we address whether the early benefits will be sustained when this is applied to a general population with type I-III TAAs. Methods: Consecutive patients undergoing repair of nonruptured Crawford extent I-III TAAs from 1/1987 to 12/2011 were identified. Patients were stratified according to operative approach (AFB/MEVP vs CS). Endpoints included long-term survival, and the composite outcome of perioperative death and paraplegia. A multivariate, risk-adjusted model was then created to determine if operative approach independently influenced outcome. Results: There were 485 patients (CS = 385 [79%]; AFB/MEVP = 100 [21%]). The cohorts differed in that the AFB/MEVP group was younger (65.8 +/- 12.5 years vs 70.9 +/- 9.7 years; P < .001), had more extent I/II aneurysms (66% vs 50.1%; P = .005), and had more chronic dissections (30.3% vs 18.9%; P = .018). Operative variables differed in that the AFB/MEVP cohort had longer operative times (434 +/- 112 minutes vs 324 +/- 98 minutes; P < .001) and higher blood turnover (6028 +/- 3473 mL vs 3581 +/- 3111 mL; P < .0001). There was no difference in the rate of intraoperative death (AFB/MEVP = 1.0% vs CS = 0.5%; P = .50), length of intensive care unit stay (AFB/MEVP = 9.6 +/- 8.6 days vs CS = 9.5 +/- 12.3 days; P = .95) or hospital length of stay (AFB/MEVP = 19.9 +/- 12.6 days vs CS = 21.6 +/- 23.5 days; P = .49). The composite perioperative death and paraplegia rate was lower in the AFB/MEVP cohort (7% vs 19%; P = .004). The multivariate model for predictors of the composite outcome showed that AFB/MEVP was protective (odds ratio, 0.39; 95% confidence interval, 0.17-0.9; P = .028). Long-term (4-year) survival was improved in the AFB/MEVP group as well (73 +/- 6% vs 60 +/- 3%; P = .004). Conclusions: AFB/MEVP is an independent predictor of improved perioperative death and paraplegia rates as well as long-term survival in patients undergoing repair of type I-III TAAs and is the preferred operative strategy. C1 [Lancaster, Robert T.; Conrad, Mark F.; Patel, Virendra I.; Cambria, Matthew R.; Ergul, Emel A.; Cambria, Richard P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Cambridge, MA 02138 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, 15 Parkman St Wang ACC 440, Boston, MA 02114 USA. EM rcambria@partners.org NR 41 TC 14 Z9 14 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 AUG PY 2013 VL 58 IS 2 BP 283 EP 290 DI 10.1016/j.jvs.2013.01.042 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 196FS UT WOS:000322759500001 PM 23796413 ER PT J AU Patel, VI Mukhopadhyay, S Ergul, E Aranson, N Conrad, MF LaMuraglia, GM Kwolek, CJ Cambria, RP AF Patel, Virendra I. Mukhopadhyay, Shankha Ergul, Emel Aranson, Nathan Conrad, Mark F. LaMuraglia, Glenn M. Kwolek, Christopher J. Cambria, Richard P. TI Impact of hospital volume and type on outcomes of open and endovascular repair of descending thoracic aneurysms in the United States Medicare population 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 STENT-GRAFT; AORTIC-ANEURYSMS; VALOR TRIAL; EXPERIENCE; ENDOGRAFT; DISEASES; SYSTEM AB Objective: Favorable outcomes of thoracic endovascular aortic repair (TEVAR) compared with open repair for descending thoracic aortic aneurysms (DTAs) have led to increasing TEVAR use. We evaluated the effect of case volume and hospital teaching status on clinical outcomes of intact DTA repair. Methods: The Medicare Provider Analysis and Review (MEDPAR) data set (2004 to 2007) was queried to identify open repair or TEVAR for DTA. Hospitals were stratified by DTA volume into high volume (HV; >= 8 cases/y) or low volume (LV; <8 cases/y) and teaching or nonteaching. The effect of hospital variables on the primary study end point of 30-day mortality and secondary end points of 30-day complications and long-term survival after open repair and TEVAR DTA repair were studied using univariate testing, multivariable regression modeling, Kaplan-Meier survival analysis, and Cox proportional hazards regression modeling. Results: We identified 763 hospitals performing 3554 open repairs and 3517 TEVARs. Overall DTA repair increased (P < .01) from 1375 in 2004 to 1987 in 2007. The proportion of hospitals performing open repair significantly decreased from 95% in 2004 to 57% in 2007 (P < .01), whereas those performing TEVAR increased (P < .01) from 24% to 76%. Overall repair type shifted from open (74% in 2004, the year before initial commercial availability of TEVAR) to TEVAR (39% open in 2007; P < .01). The fraction of open repairs at LV hospitals decreased from 56% in 2004 to 44% in 2007 (P < .01), whereas TEVAR increased from 24% in 2004 to 51% in 2007 (P < .01). Overall mortality during the study interval for open repair was 15% at LV hospitals vs 11% at HV hospitals (P < .01), whereas TEVAR mortality was similar, at 3.9% in LV vs 5.5% in HV hospitals (P = .43). LV was independently associated with increased mortality after open repair (odds ratio, 1.4; 95% confidence interval, 1.1-1.8; P < .01) but not after TEVAR. There was no independent effect of hospital teaching status on mortality or complications after open repair or TEVAR repair. Conclusions: The total number of DTA repairs has significantly increased. Operative mortality for TEVAR is independent of hospital volume and type, whereas mortality after open surgery is lower at HV hospitals, suggesting that TEVAR can be safely performed across a spectrum of hospitals, whereas open surgery should be performed only at HV hospitals. C1 [Patel, Virendra I.; Mukhopadhyay, Shankha; Ergul, Emel; Aranson, Nathan; Conrad, Mark F.; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Cambria, Richard P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Cambridge, MA 02138 USA. RP Patel, VI (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM vpatel4@partners.org NR 22 TC 13 Z9 15 U1 0 U2 2 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 AUG PY 2013 VL 58 IS 2 BP 346 EP 354 DI 10.1016/j.jvs.2013.01.035 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 196FS UT WOS:000322759500012 PM 23541550 ER PT J AU Geraghty, PJ Mewissen, MW Jaff, MR Ansel, GM AF Geraghty, Patrick J. Mewissen, Mark W. Jaff, Michael R. Ansel, Gary M. CA VIBRANT Investigators TI Three-year results of the VIBRANT trial of VIABAHN endoprosthesis versus bare nitinol stent implantation for complex superficial femoral artery occlusive disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID HEALTH SURVEY SF-36; BALLOON ANGIOPLASTY; RANDOMIZED-TRIAL; CLINICAL-TRIALS; CLAUDICATION; PERFORMANCE; ISCHEMIA; QUALITY; LESIONS; TESTS AB Objective: The predominant mode of bare nitinol stent failure is diffuse in-stent restenosis, and failure rates correlate to the length and complexity of the treated lesion. Addition of an expanded polytetrafluoroethylene lining to a nitinol stent frame, as found in the VIABAHN endoprosthesis, mitigates the ingrowth of intimal hyperplasia. We compared the long-term outcomes of complex superficial femoral artery disease intervention using the VIABAHN endoprosthesis to those obtained with bare nitinol stent implantation. Methods: One hundred forty-eight patients with symptomatic complex superficial femoral artery disease (TransAtlantic Inter-Society Consensus I class C and D lesions, accompanied by intermittent claudication or ischemic rest pain) were randomized to endovascular intervention using either bare nitinol stent implantation (76 patients) or nonheparin-bonded VIABAHN endoprosthesis deployment (72 patients). Patency, limb hemodynamics, and quality of life were evaluated at 1, 6, 12, 24, and 36 months following intervention. Results: The average treated lesion measured 18 +/- 8 cm in length, and 58.8% of lesions displayed segmental or complete occlusion. At 3 years, primary patency rates (defined by peak systolic velocity ratio <= 2.0 and no target lesion revascularization) did not significantly differ between patients treated with the VIABAHN stent graft and those who received a bare nitinol stent (24.2% vs 25.9%; P = .392). Stent fractures were significantly more common in bare nitinol stents (50.0%) than in the VIABAHN endoprostheses (2.6%). Primary-assisted patency rates were higher in those receiving bare nitinol stents than the VIABAHN stent graft (88.8% vs 69.8%; P = .04), although secondary patency rates did not differ between bare nitinol stent and stent graft recipients (89.3% vs 79.5%; P = .304). There were no instances of procedure-related mortality or amputation. The hemodynamic improvement and quality measures improved equally in both groups. Conclusions: The long-term outcomes of complex superficial femoral artery disease intervention using the VIABAHN endograft and bare nitinol stents are similar. Although primary patency rates are low in both study arms, excellent primary-assisted and secondary patency rates were achieved, with sustained augmentation of limb perfusion and quality-of-life measures. Patency rates diminish most rapidly in the first year after device implantation. C1 [Geraghty, Patrick J.] Washington Univ, Sch Med, Dept Surg, Vasc Surg Sect, St Louis, MO 63110 USA. [Mewissen, Mark W.] St Lukes Hosp, Aurora Cardiovasc Serv, Milwaukee, WI USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ansel, Gary M.] Riverside Methodist Hosp, Dept Med, Columbus, OH 43214 USA. RP Geraghty, PJ (reprint author), Washington Univ, Sch Med, Dept Surg, Vasc Surg Sect, 660 S Euclid Ave,Campus Box 8109, St Louis, MO 63110 USA. EM geraghtyp@wustl.edu RI Sternbergh, W. Charles/B-3227-2011 NR 18 TC 39 Z9 46 U1 0 U2 12 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 AUG PY 2013 VL 58 IS 2 BP 386 EP 395 DI 10.1016/j.jvs.2013.01.050 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 196FS UT WOS:000322759500018 PM 23676191 ER PT J AU Economopoulos, KP Martinou, E Hakimian, S Schizas, D Georgopoulos, S Tsigris, C Bakoyiannis, CN AF Economopoulos, Konstantinos P. Martinou, Eirini Hakimian, Shahrad Schizas, Dimitrios Georgopoulos, Sotirios Tsigris, Christos Bakoyiannis, Chris N. TI An overview of laparoscopic techniques in abdominal aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RETROPERITONEAL APPROACH; HYBRID PROCEDURES; SURGERY; TRIAL; GRAFT; MORTALITY; DISEASE; BYPASS AB Background: Since 1993, various laparoscopic techniques have been developed to make laparoscopic treatment of abdominal aortic aneurysms (AAAs) a possible therapeutic alternative. We aim to review all published clinical studies on laparoscopic surgery of AAAs and juxtarenal abdominal aortic aneurysms (JAAAs). Methods: A thorough search of English-language literature published between January 1966 and December 2012 was performed. Studies that reported the results of laparoscopic surgical procedures as the intended repair strategy in patients with AAAs and JAAAs were selected using specific inclusion criteria. Only case series containing more than five patients were included. Outcome measures of eligible studies were extracted, tabulated, and then analyzed cumulatively, using a purely descriptive approach. Results: Fourteen studies were included in the analysis encompassing 933 patients with AAAs (mean age, 68.5 years; age range, 46-88) averaging 55.8 mm in diameter and 96 patients with JAAAs (mean age, 71 years; age range, 50-81) averaging 57 mm in diameter. The mean follow-up was 15.3 months for the AAA cases and 32.8 months for the JAAA cases. Hand-assisted laparoscopy, in particular, had a low 30-day mortality rate, short cross-clamping and operative times, few perioperative and postoperative complications, high graft patency rates, and short length of both hospital and intensive care unit stay. Conclusions: Laparoscopic surgical procedures are a safe, feasible, and worthwhile alternative for patients with AAAs and JAAAs. Hand-assisted laparoscopy, in particular, was associated with low morbidity and mortality and short hospital and intensive care unit stay. However, the final decision regarding the best laparoscopic treatment should be left to the surgeon because of the limits of the data. C1 [Economopoulos, Konstantinos P.; Hakimian, Shahrad] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Economopoulos, Konstantinos P.; Georgopoulos, Sotirios; Tsigris, Christos; Bakoyiannis, Chris N.] Univ Athens, Dept Surg 1, Vasc Dept, Laiko Gen Hosp, Athens, Greece. [Economopoulos, Konstantinos P.; Martinou, Eirini; Schizas, Dimitrios] Soc Jr Doctors, Athens, Greece. [Martinou, Eirini] St Georges Hosp Healthcare NHS Trust, London, England. [Hakimian, Shahrad] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Economopoulos, KP (reprint author), Massachusetts Gen Hosp, Dept Surg, 65 Martha Rd,Apt 10C, Boston, MA 02114 USA. EM economopoulos@sni.gr OI Economopoulos, Konstantinos/0000-0003-4856-0405 NR 38 TC 4 Z9 5 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 AUG PY 2013 VL 58 IS 2 BP 512 EP 520 DI 10.1016/j.jvs.2013.04.059 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 196FS UT WOS:000322759500042 PM 23890444 ER PT J AU Martinez, AA Zaldivar, Y Hong, CC Alvarado-Mora, MV Smith, R Ortiz, AY Pinho, JRR Cristina, J Pascale, JM AF Augusto Martinez, Alexander Zaldivar, Yamitzel Hong, Chen Ch Viviana Alvarado-Mora, Monica Smith, Rebecca Ortiz, Alma Y. Rebello Pinho, Joao Renato Cristina, Juan Miguel Pascale, Juan TI Molecular characterisation of hepatitis B virus in the resident Chinese population in Panama City SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article DE hepatitis B; Panama; Bayesian analysis; genotype C1; genotype B2 ID BASAL CORE PROMOTER; SURFACE-ANTIGEN; EVOLUTIONARY HISTORY; GENOTYPE-F; HEPATOCELLULAR-CARCINOMA; PHYLOGENETIC ANALYSIS; GENETIC DIVERSITY; C VIRUS; PREVALENCE; MUTATIONS AB Despite the effectiveness of current hepatitis B virus (HBV) vaccines, it is estimated that 350 million individuals suffer from chronic HBV infection and more than 50% of these affected individuals live on the Asian continent. Panama is a country with a great diversity of foreign groups; the Chinese community is a large example of this phenomenon. There is an urgent need to perform studies that evaluate the prevalence and the genetic diversity of HBV in this community. This study aimed to evaluate the prevalence of HBV and its genotypes and mutant variants in the Chinese population residing in Panama. In total, 320 subjects were enrolled in the study. Forty-two subjects (13.1%) were positive for HBsAg and HBV-DNA from 18 subjects revealed the presence of genotypes B2 and C1. Secondary mutations associated with drug resistance at positions rtV207L and rtN239T of the reverse transcriptase gene were identified. Additionally, the mutation pair A1762T/G1764A was found in three samples and the mutation G1896A was detected in an HBeAg-negative subject. In conclusion, to our knowledge, this is the first study to report high HBV prevalence rates in resident ethnic Chinese in Central America and the presence of genotypes B2 and C1 in this region. C1 [Augusto Martinez, Alexander; Zaldivar, Yamitzel; Smith, Rebecca; Ortiz, Alma Y.; Miguel Pascale, Juan] Gorgas Mem Inst Hlth Studies, Panama City, Panama. [Augusto Martinez, Alexander] Acharya Nagarjuna Univ, Dept Biotechnol, Guntur, India. [Augusto Martinez, Alexander] Inst Invest Cient & Serv Alta Tecnol AIP, Clayton, Vic, Panama. [Hong, Chen Ch] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Viviana Alvarado-Mora, Monica; Rebello Pinho, Joao Renato] Univ Sao Paulo, Fac Med, Dept Gastroenterol, Lab Gastroenterol & Hepatol Trop, Sao Paulo, Brazil. [Cristina, Juan] Univ Republica, Fac Ciencias, Ctr Invest Nucl, Montevideo, Uruguay. [Miguel Pascale, Juan] Univ Panama, Sch Med, Panama City, Panama. RP Pascale, JM (reprint author), Gorgas Mem Inst Hlth Studies, Panama City, Panama. EM jpascale@gorgas.gob.pa RI Pinho, Joao/G-2850-2012; Martinez , Alexander/F-9601-2012 OI Pinho, Joao/0000-0003-3999-0489; Martinez , Alexander/0000-0002-7816-3040 FU SENACYT-PANAMA [FID09-050]; SENACYT-IFARHU FX SENACYT-PANAMA (FID09-050); AAM was supported by a fellowship from SENACYT-IFARHU. NR 51 TC 4 Z9 4 U1 0 U2 2 PU FUNDACO OSWALDO CRUZ PI RIO DE JANEIRO, RJ PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PD AUG PY 2013 VL 108 IS 5 BP 541 EP 547 DI 10.1590/0074-0276108052013002 PG 7 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 192XI UT WOS:000322520800002 PM 23903967 ER PT J AU Gavrieli, A Fragopoulou, E Mantzoros, CS Yannakoulia, M AF Gavrieli, Anna Fragopoulou, Elizabeth Mantzoros, Christos S. Yannakoulia, Mary TI Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Caffeine; Obesity; Women ID TYPE-2 DIABETES-MELLITUS; HORMONE-BINDING GLOBULIN; DECAFFEINATED COFFEE; PROSPECTIVE COHORT; CHLOROGENIC ACID; MENSTRUAL-CYCLE; TOLERANCE TEST; BLOOD-GLUCOSE; DOUBLE-BLIND; CONSUMPTION AB Objective. To examine the effects of different coffee amounts on blood glucose and insulin concentrations of healthy volunteers, and to assess potential effect modification by sex and body mass index category. Materials/Methods. Thirty-three volunteers [16 female/17 male, 16 normal-weight and 17 overweight/obese, 27.3 +/- 7.2 (19-44) y] took part in this randomized, crossover study. In the morning of each experimental day volunteers received a standardized meal along with 200 mL of water or instant coffee containing either 3 or 6 mg of caffeine/kg body weight. Blood samples were obtained and analyzed for glucose and insulin concentrations in the fasting state, immediately after meal/drink consumption and at standard time points for the next 3 h thereafter. Results. Coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample. Glucose incremental area under the curve (IAUC) was significantly different between interventions (P = .009) with both coffee amounts inducing a greater area compared to water. Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (P-IAUC = .05) and overweight/obese participants (P-IAUC = .03). Furthermore, coffee, mainly the 6 mg dose, could be lowering insulin concentrations the first 30 min after its consumption compared to water in men and overweight/obese participants. Conclusions. Coffee exerts an acute effect on postprandial glucose and insulin concentrations. This effect may be modified by sex and overweight/obese status. Future research is necessary to elucidate underlying mechanisms. (C) 2013 Elsevier Inc. All rights reserved. C1 [Gavrieli, Anna; Fragopoulou, Elizabeth; Yannakoulia, Mary] Harokopio Univ, Dept Nutr & Dietet, Athens 17671, Greece. [Mantzoros, Christos S.] VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr Boston, Div Endocrinol Diabet & Metab, Boston, MA USA. RP Yannakoulia, M (reprint author), Harokopio Univ, Dept Nutr & Dietet, Athens 17671, Greece. EM myiannak@hua.gr FU Department of Nutrition and Dietetics, Harokopio University. FX The study was supported through a research funding from the Graduate Program of the Department of Nutrition and Dietetics, Harokopio University. NR 40 TC 10 Z9 10 U1 5 U2 26 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2013 VL 62 IS 8 BP 1099 EP 1106 DI 10.1016/j.metabol.2013.02.003 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 195ED UT WOS:000322684200011 PM 23498899 ER PT J AU Moon, HS Dincer, F Mantzoros, CS AF Moon, Hyun-Seuk Dincer, Fadime Mantzoros, Christos S. TI Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Irisin; Signaling; Hippocampal neurogenesis ID ALZHEIMERS-DISEASE; SKELETAL-MUSCLE; ADULT NEUROGENESIS; EXERCISE; BRAIN; STRESS; EXPRESSION; OBESITY; AMYLIN; LEPTIN AB Aims/Hypothesis. Irisin is a novel, myocyte secreted, hormone that has been proposed to mediate the beneficial effects of exercise on metabolism. Irisin is expressed, at lower levels, in human brains and knock-down of the precursor of irisin, FNDC5, decreases neural differentiation of mouse embryonic stem cells. No previous studies have evaluated whether irisin may directly regulate hippocampal neurogenesis in mouse hippocampal neuronal (HN) cells. Methods. Hippocampal neurogenesis and irisin signaling were studied in vitro using mouse H19-7 HN cell lines. Results. We observed that cell proliferation is regulated by irisin in a dose-dependent manner in mouse H19-7 HN cells. Specifically, physiological concentrations of irisin, 5 to 10 nmol/L, had no effect on cell proliferation when compared to control. By contrast, pharmacological concentrations of irisin, 50 to 100 nmol/L, increased cell proliferation when compared to control. Similar to these results regarding irisin's effects on cell proliferation, we also observed that only pharmacological concentrations of irisin increased STAT3, but not AMPK and/or ERK, activation. Finally, we observed that irisin did not activate either microtubule-associated protein 2, a specific neurite outgrowth marker, or Synapsin, a specific synaptogenesis marker in mouse H19-7 HN cells. Conclusions/Interpretations. Our data suggest that irisin, in pharmacological concentrations, increases cell proliferation in mouse H19-7 HN cells via STAT3, but not AMPK and/or ERK, signaling pathways. By contrast, neither physiological nor pharmacological concentrations of irisin alter markers of hippocampal neurogenesis in mouse H19-7 HN cell lines. (C) 2013 Elsevier Inc. All rights reserved. C1 [Moon, Hyun-Seuk; Dincer, Fadime; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Moon, HS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM hmoon@bidmc.harvard.edu RI Moon, Hyun-Seuk/G-8576-2015 OI Moon, Hyun-Seuk/0000-0002-5216-2090 FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913]; Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1] FX The Mantzoros Laboratory was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785,79929 and 81913, and by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NR 32 TC 44 Z9 49 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2013 VL 62 IS 8 BP 1131 EP 1136 DI 10.1016/j.metabol.2013.04.007 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 195ED UT WOS:000322684200015 PM 23664146 ER PT J AU Holstila, M Virtanen, KA Gronroos, TJ Laine, J Lepomaki, V Saunavaara, J Lisinen, I Komu, M Hannukainen, LC Nuutila, P Parkkola, R Borra, RJH AF Holstila, Milja Virtanen, Kirsi A. Gronroos, Tove J. Laine, Jukka Lepomaki, Virva Saunavaara, Jani Lisinen, Irina Komu, Markku Hannukainen, Lama C. Nuutila, Pirjo Parkkola, Riitta Borra, Ronald J. H. TI Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: A validation study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Cold exposure; (18)FDG-PET; Rat ID ADULT HUMANS; OUTDOOR TEMPERATURE; 4.7 TESLA; FAT; HIBERNOMA; IDENTIFICATION; WATER; PREVALENCE; OBESITY; MEN AB Objective. The aim of this study was to evaluate and validate magnetic resonance imaging (MRI) for the visualization and quantification of brown adipose tissue (BAT) in vivo in a rat model. We hypothesized that, based on differences in tissue water and lipid content, MRI could reliably differentiate between BAT and white adipose tissue (WAT) and could therefore be a possible alternative for 18 F-Fluorodeoxyglucose Positron Emission Tomography ((18)FDG-PET), the current gold standard for non-invasive BAT quantification. Materials/Methods. Eleven rats were studied using both (18)FDG-PET/CT and MRI (1.5 T). A dual echo (in-and-out-of-phase) sequence was used, both with and without spectral presaturation inversion recovery (SPIR) fat suppression (DUAL-SPIR) to visualize BAT, after which all BAT was surgically excised. The BAT volume measurements obtained via (18)FDG-PET/CT and DUAL-SPIR MR were quantitatively compared with the histological findings. All study protocols were reviewed and approved by the local ethics committee. Results. The BAT mass measurements that were obtained using DUAL-SPIR MR subtraction images correlated better with the histological findings (P = 0.017, R = 0.89) than did the measurements obtained using (18)FDG-PET/CT (P = 0.78, R = 0.15), regardless of the BAT metabolic activation state. Additionally, the basic feasibility of the DUAL-SPIR method was demonstrated in three human pilot subjects. Conclusions. This study demonstrates the potential for MRI to reliably detect and quantify BAT in vivo. MRI can provide information beyond that provided by (18)FDG-PET imaging, and its ability to detect BAT is independent of its metabolic activation state. Additionally, MRI is a low-cost alternative that does not require radiation. (C) 2013 Elsevier Inc. All rights reserved. C1 [Holstila, Milja; Saunavaara, Jani; Komu, Markku; Parkkola, Riitta; Borra, Ronald J. H.] Turku Univ Hosp, Med Imaging Ctr Southwest Finland, FIN-20520 Turku, Finland. [Virtanen, Kirsi A.; Gronroos, Tove J.; Lepomaki, Virva; Lisinen, Irina; Hannukainen, Lama C.; Nuutila, Pirjo; Borra, Ronald J. H.] Univ Turku, Turku PET Ctr, Turku, Finland. [Virtanen, Kirsi A.; Gronroos, Tove J.; Laine, Jukka; Lepomaki, Virva; Lisinen, Irina; Hannukainen, Lama C.; Nuutila, Pirjo; Borra, Ronald J. H.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Laine, Jukka] Univ Turku, Dept Pathol, Turku, Finland. [Nuutila, Pirjo] Univ Turku, Dept Med, Turku, Finland. [Borra, Ronald J. H.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM riitta.parkkola@tyks.fi RI Nuutila, Pirjo/J-2087-2012; Saunavaara, Virva/M-5594-2016; OI Saunavaara, Virva/0000-0001-7858-5924; Borra, Ronald/0000-0001-8072-1243; Hannukainen, Jarna/0000-0002-8692-4049 FU Academy of Finland; University of Turku; Turku University Hospital; Abo Akademi University; Sigrid Juselius Foundation; Instrumentarium Research Foundation; Paulo Foundation; Finnish Medical Foundation FX This study was conducted within the Finnish Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research, which is supported by the Academy of Finland, University of Turku, Turku University Hospital and Abo Akademi University. Additionally, RJHB received personal research grants from the Sigrid Juselius. Foundation, the Instrumentarium Research Foundation, the Academy of Finland, the Paulo Foundation and the Finnish Medical Foundation. NR 31 TC 13 Z9 14 U1 1 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2013 VL 62 IS 8 BP 1189 EP 1198 DI 10.1016/j.metabol.2013.03.002 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 195ED UT WOS:000322684200021 PM 23587549 ER PT J AU Zhao, ML Gupta, V Raj, L Roussel, M Bei, M AF Zhao, Minglian Gupta, Vandana Raj, Lakshmi Roussel, Martine Bei, Marianna TI A Network of Transcription Factors Operates during Early Tooth Morphogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TATA-BINDING PROTEIN; LIM DOMAIN; SNAIL GENE; P19(INK4D) EXPRESSION; HOMEODOMAIN PROTEINS; CONFERS RESISTANCE; MULTIPLE ROLES; HOMEOBOX GENES; NEURAL CREST; CELL-CYCLE AB Improving the knowledge of disease-causing genes is a unique challenge in human health. Although it is known that genes causing similar diseases tend to lie close to one another in a network of protein-protein or functional interactions, the identification of these protein-protein networks is difficult to unravel. Here, we show that Msx1, Snail, Lhx6, Lhx8, Sp3, and Lef1 interact in vitro and in vivo, revealing the existence of a novel context-specific protein network. These proteins are all expressed in the neural crest-derived dental mesenchyme and cause tooth agenesis disorder when mutated in mouse and/or human. We also identified an in vivo direct target for Msx1 function, the cyclin D-dependent kinase (CDK) inhibitor p19(ink4d), whose transcription is differentially modulated by the protein network. Considering the important role of p19(ink4d) as a cell cycle regulator, these results provide evidence for the first time of the unique plasticity of the Msx1-dependent network of proteins in conferring differential transcriptional output and in controlling the cell cycle through the regulation of a cyclin D-dependent kinase inhibitor. Collectively, these data reveal a novel protein network operating in the neural crest-derived dental mesenchyme that is relevant for many other areas of developmental and evolutionary biology. C1 [Zhao, Minglian; Bei, Marianna] Forsyth Inst, Ctr Regenerat Dev Biol, Cambridge, MA USA. [Bei, Marianna] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bei, Marianna] Harvard Univ, Sch Med, Boston, MA USA. [Gupta, Vandana; Raj, Lakshmi] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Roussel, Martine] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Bei, M (reprint author), Forsyth Inst, Ctr Regenerat Dev Biol, Cambridge, MA USA. EM mbei@partners.org FU NIH [K22 DE 14230, RO3 DE 018415, RO1 DE 19226]; Harvard Medical School; Shiseido, Inc. FX The study was supported by funds from NIH (grants K22 DE 14230, RO3 DE 018415, and RO1 DE 19226), Harvard Medical School (Milton Fund Award), and Shiseido, Inc., to M. B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 78 TC 6 Z9 6 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2013 VL 33 IS 16 BP 3099 EP 3112 DI 10.1128/MCB.00524-13 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188VM UT WOS:000322224400004 PM 23754753 ER PT J AU Park, K Li, Q Rask-Madsen, C Mima, A Mizutani, K Winnay, J Maeda, Y D'Aquino, K White, MF Feener, EP King, GL AF Park, Kyoungmin Li, Qian Rask-Madsen, Christian Mima, Akira Mizutani, Koji Winnay, Jonathon Maeda, Yasutaka D'Aquino, Katharine White, Morris F. Feener, Edward P. King, George L. TI Serine Phosphorylation Sites on IRS2 Activated by Angiotensin II and Protein Kinase C To Induce Selective Insulin Resistance in Endothelial Cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR-I; GLYCOGEN-SYNTHASE KINASE-3; NITRIC-OXIDE SYNTHASE; RECEPTOR SUBSTRATE-1; DIFFERENTIAL ROLES; SKELETAL-MUSCLE; FATTY-ACIDS; INHIBITION; SER(307); GLUCOSE AB Protein kinase C (PKC) activation, induced by hyperglycemia and angiotensin II (AngII), inhibited insulin-induced phosphorylation of Akt/endothelial nitric oxide (eNOS) by decreasing tyrosine phosphorylation of IRS2 (p-Tyr-IRS2) in endothelial cells. PKC activation by phorbol ester (phorbol myristate acetate [PMA]) reduced insulin-induced p-Tyr-IRS2 by 46% +/- 13% and, similarly, phosphorylation of Akt/eNOS. Site-specific mutational analysis showed that PMA increased serine phosphorylation at three sites on IRS2 (positions 303, 343, and 675), which affected insulin-induced tyrosine phosphorylation of IRS2 at positions 653, 671, and 911 (p-Tyr-IRS2) and p-Akt/eNOS. Specific PKC beta 2 activation decreased p-Tyr-IRS2 and increased the phosphorylation of two serines (Ser303 and Ser675) on IRS2 that were confirmed in cells overexpressing single point mutants of IRS2 (S303A or S675A) containing a PKC beta 2-dominant negative or selective PKC beta inhibitor. AngII induced phosphorylation only on Ser303 of IRS2 and inhibited insulin-induced p-Tyr911 of IRS2 and p-Akt/eNOS, which were blocked by an antagonist of AngII receptor I, losartan, or overexpression of single mutant S303A of IRS2. Increases in p-Ser303 and p-Ser675 and decreases in p-Tyr911 of IRS2 were observed in vessels of insulin-resistant Zucker fatty rats versus lean rats. Thus, AngII or PKC beta activation can phosphorylate Ser303 and Ser675 in IRS2 to inhibit insulin-induced p-Tyr911 and its anti-atherogenic actions (p-Akt/eNOS) in endothelial cells. C1 [Park, Kyoungmin; Li, Qian; Rask-Madsen, Christian; Mima, Akira; Mizutani, Koji; Winnay, Jonathon; Maeda, Yasutaka; Feener, Edward P.; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02115 USA. [D'Aquino, Katharine; White, Morris F.] Childrens Hosp Boston, Boston, MA USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02115 USA. EM George.king@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Disease [R01DK053105] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Disease (R01DK053105). NR 42 TC 20 Z9 20 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2013 VL 33 IS 16 BP 3227 EP 3241 DI 10.1128/MCB.00506-13 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188VM UT WOS:000322224400014 PM 23775122 ER PT J AU Woo, CJ Kharchenko, PV Daheron, L Park, PJ Kingston, RE AF Woo, Caroline J. Kharchenko, Peter V. Daheron, Laurence Park, Peter J. Kingston, Robert E. TI Variable Requirements for DNA-Binding Proteins at Polycomb-Dependent Repressive Regions in Human HOX Clusters SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; RNA-POLYMERASE-II; HISTONE METHYLTRANSFERASE ACTIVITY; YIN YANG 1; TARGET GENES; DEVELOPMENTAL REGULATORS; RESPONSE ELEMENTS; ES CELLS; COMPLEXES; GENOME AB Polycomb group (PcG)-mediated repression is an evolutionarily conserved process critical for cell fate determination and maintenance of gene expression during embryonic development. However, the mechanisms underlying PcG recruitment in mammals remain unclear since few regulatory sites have been identified. We report two novel prospective PcG-dependent regulatory elements within the human HOXB and HOXC clusters and compare their repressive activities to a previously identified element in the HOXD cluster. These regions recruited the PcG proteins BMI1 and SUZ12 to a reporter construct in mesenchymal stem cells and conferred repression that was dependent upon PcG expression. Furthermore, we examined the potential of two DNA-binding proteins, JARID2 and YY1, to regulate PcG activity at these three elements. JARID2 has differential requirements, whereas YY1 appears to be required for repressive activity at all 3 sites. We conclude that distinct elements of the mammalian HOX clusters can recruit components of the PcG complexes and confer repression, similar to what has been seen in Drosophila. These elements, however, have diverse requirements for binding factors, which, combined with previous data on other loci, speaks to the complexity of PcG targeting in mammals. C1 [Woo, Caroline J.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kharchenko, Peter V.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Daheron, Laurence] Harvard Stem Cell Inst, Cambridge, MA USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM Kingston@molbio.mgh.harvard.edu FU National Institutes of Health [GM43901, HG003141, GM082798]; NRSA [GM072265] FX This work was supported by grants GM43901 and HG003141 from the National Institutes of Health for R. E. K. and C.J.W. C.J.W. was supported by NRSA GM072265. P.J.K. and P. V. K. were supported by NIH grant GM082798. NR 42 TC 17 Z9 17 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2013 VL 33 IS 16 BP 3274 EP 3285 DI 10.1128/MCB.00275-13 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188VM UT WOS:000322224400017 PM 23775117 ER PT J AU Steele, JW Ju, S Lachenmayer, ML Liken, J Stock, A Kim, SH Delgado, LM Alfaro, IE Bernales, S Verdile, G Bharadwaj, P Gupta, V Barr, R Friss, A Dolios, G Wang, R Ringe, D Protter, AA Martins, RN Ehrlich, ME Yue, Z Petsko, GA Gandy, S AF Steele, J. W. Ju, S. Lachenmayer, M. L. Liken, J. Stock, A. Kim, S. H. Delgado, L. M. Alfaro, I. E. Bernales, S. Verdile, G. Bharadwaj, P. Gupta, V. Barr, R. Friss, A. Dolios, G. Wang, R. Ringe, D. Protter, A. A. Martins, R. N. Ehrlich, M. E. Yue, Z. Petsko, G. A. Gandy, S. TI Latrepirdine stimulates autophagy and reduces accumulation of alpha-synuclein in cells and in mouse brain SO MOLECULAR PSYCHIATRY LA English DT Article DE autophagy; proteotoxicity; alpha-synuclein; therapeutics ID ALZHEIMERS-DISEASE; HUNTINGTONS-DISEASE; IN-VIVO; DIMEBON; YEAST; COGNITION; TOXICITY; BETA; PROTEINOPATHY; AGGREGATION AB Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer's disease and Huntington's disease (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including A beta 42 and gamma-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae. We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including alpha-synuclein (alpha-syn), the amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene; htt-103Q). Latrepirdine effects on alpha-syn clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wildtype mice. Latrepirdine only protected yeast against the cytotoxicity associated with alpha-syn, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of alpha-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate alpha-syn accumulation in transgenic mouse models of alpha-syn neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust proautophagic/anti-neurodegeneration compounds, which might yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy body dementia, rapid eye movement (REM) sleep disorder and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities. C1 [Steele, J. W.; Lachenmayer, M. L.; Stock, A.; Kim, S. H.; Ehrlich, M. E.; Yue, Z.; Gandy, S.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Steele, J. W.; Stock, A.; Kim, S. H.; Gandy, S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Steele, J. W.; Stock, A.; Kim, S. H.; Gandy, S.] Mt Sinai Sch Med, Mt Sinai Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Steele, J. W.] Rockefeller Univ, Lab Mol & Cellular Neurosci, New York, NY 10021 USA. [Ju, S.; Liken, J.; Ringe, D.; Petsko, G. A.] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biochem, Waltham, MA 02254 USA. [Ju, S.; Liken, J.; Ringe, D.; Petsko, G. A.] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Chem, Waltham, MA 02254 USA. [Lachenmayer, M. L.] Univ Bonn, Dept Neurol, Bonn, Germany. [Delgado, L. M.] Univ Andres Bello, Fac Ciencias Biol, Santiago, Chile. [Alfaro, I. E.; Bernales, S.] Fdn Ciencia & Vida, Santiago, Chile. [Bernales, S.; Protter, A. A.] Medivation Inc, San Francisco, CA USA. [Verdile, G.; Bharadwaj, P.; Gupta, V.; Barr, R.; Martins, R. N.] Edith Cowan Univ, Sch Med Sci, Ctr Excellence Alzheimers Dis Res & Care, Churchlands, WA 6018, Australia. [Friss, A.; Dolios, G.; Wang, R.; Ehrlich, M. E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Martins, R. N.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Crawley, WA, Australia. [Martins, R. N.] Hollywood Private Hosp, Sir James McCusker Alzheimers Dis Res Unit, Nedlands, WA, Australia. [Ehrlich, M. E.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Yue, Z.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Petsko, G. A.] Cornell Univ, Dept Neurol & Neurosci, Weill Med Coll, New York, NY 10021 USA. [Gandy, S.] James J Peters VA Med Ctr, Bronx, NY USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM samuel.gandy@mssm.edu RI Wang, Rong/A-8721-2009 FU National Institute of General Medical Sciences [T32GM062754]; Deutsche Forschungsgemeinschaft; NHMRC [APP1009295]; McCusker Alzheimer's Research Foundation [PFB-16]; Fidelity Biosciences Research Initiative; Cure Alzheimer's Fund; US Department of Veterans Affairs; NIH [P01AG10491, P50AG05138, P30 NS061777, S10 RR022415, R01NS060123, U54RR022220] FX The work in this manuscript was used in a dissertation by JWS as partial requirement for the fulfillment of the PhD degree. JWS is a trainee in the Integrated Pharmacological Sciences Training Program supported by grant T32GM062754 from the National Institute of General Medical Sciences. MLL was supported by the Deutsche Forschungsgemeinschaft. SG is a member of the Oligomer Research Consortium of the Cure Alzheimer's Fund. We acknowledge the generous support of the NH&MRC (APP1009295 to RM, GV, SG), McCusker Alzheimer's Research Foundation (RM, GV), Conicyt (PFB-16 to SB), Fidelity Biosciences Research Initiative (SJ, JL, DR, GAP), Cure Alzheimer's Fund (SG), the US Department of Veterans Affairs (SG), and the NIH (P01AG10491 to SG; P50AG05138 to Mary Sano; P30 NS061777 and S10 RR022415 to RW; R01NS060123 and U54RR022220 to ZY). We would like to thank Rosilyn Kazanjian for her gift in memory of Powel Kazanjian. We would also like to thank Loren E Khan and Justine Bonet for technical assistance in animal colony management and Dr Yun Zhong for technical support, and Dr Kostas Vekrellis (Foundation for Biomedical Research of the Academy of Athens, Athens, Greece) for generously providing the tet-off inducible alpha-syn overexpressing SH-SY5Y neuro-blastoma cell line. NR 35 TC 28 Z9 29 U1 5 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD AUG PY 2013 VL 18 IS 8 BP 882 EP 888 DI 10.1038/mp.2012.115 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 191XM UT WOS:000322448400009 PM 22869031 ER PT J AU Steele, JW Lachenmayer, ML Ju, S Stock, A Liken, J Kim, SH Delgado, LM Alfaro, IE Bernales, S Verdile, G Bharadwaj, P Gupta, V Barr, R Friss, A Dolios, G Wang, R Ringe, D Fraser, P Westaway, D St George-Hyslop, PH Szabo, P Relkin, NR Buxbaum, JD Glabe, CG Protter, AA Martins, RN Ehrlich, ME Petsko, GA Yue, Z Gandy, S AF Steele, J. W. Lachenmayer, M. L. Ju, S. Stock, A. Liken, J. Kim, S. H. Delgado, L. M. Alfaro, I. E. Bernales, S. Verdile, G. Bharadwaj, P. Gupta, V. Barr, R. Friss, A. Dolios, G. Wang, R. Ringe, D. Fraser, P. Westaway, D. St George-Hyslop, P. H. Szabo, P. Relkin, N. R. Buxbaum, J. D. Glabe, C. G. Protter, A. A. Martins, R. N. Ehrlich, M. E. Petsko, G. A. Yue, Z. Gandy, S. TI Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model SO MOLECULAR PSYCHIATRY LA English DT Article DE Alzheimer's disease; amyloid; autophagy; therapeutics ID AMYLOID-BETA LEVELS; HUNTINGTONS-DISEASE; DIMEBON; DEFICITS; AUTOPHAGY; MTOR; INHIBITION; DISCOVERY; RAT AB Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine (LAT)-stimulated amyloid precursor protein (APP) catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer's disease (AD). We utilized several mammalian cellular models to determine whether LAT regulates mammalian target of rapamycin (mTOR) and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered LAT prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with LAT led to enhanced mTOR-and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of A beta 42 and alpha-synuclein. We conclude that LAT possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying LAT effects on neurogenesis, autophagy and behavior might warranty the further study of LAT as a potentially viable lead compound that might yield more consistent clinical benefit following the optimization of its pro-neurogenic, pro-autophagic and/or pro-cognitive activities. C1 [Steele, J. W.; Lachenmayer, M. L.; Stock, A.; Kim, S. H.; Ehrlich, M. E.; Yue, Z.; Gandy, S.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Steele, J. W.; Kim, S. H.; Buxbaum, J. D.; Gandy, S.] Dept Psychiat, New York, NY USA. [Steele, J. W.; Kim, S. H.; Buxbaum, J. D.; Gandy, S.] Mt Sinai Alzheimers Dis Res Ctr, New York, NY USA. [Steele, J. W.] Rockefeller Univ, Lab Mol & Cellular Neurosci, New York, NY 10021 USA. [Lachenmayer, M. L.] Univ Bonn, Dept Neurol, Bonn, Germany. [Ju, S.; Liken, J.; Ringe, D.; Petsko, G. A.] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biochem, Waltham, MA 02254 USA. [Ju, S.; Liken, J.; Ringe, D.; Petsko, G. A.] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Chem, Waltham, MA 02254 USA. [Delgado, L. M.] Univ Andres Bello, Fac Ciencias Biol, Santiago, Chile. [Alfaro, I. E.; Bernales, S.] Fdn Ciencia & Vida, Santiago, Chile. [Bernales, S.; Protter, A. A.] Medivation Inc, San Francisco, CA USA. [Verdile, G.; Bharadwaj, P.; Gupta, V.; Barr, R.; Martins, R. N.] Edith Cowan Univ, Sch Med Sci, Ctr Excellence Alzheimers Dis Res & Care, Perth, WA, Australia. [Friss, A.; Dolios, G.; Wang, R.; Buxbaum, J. D.; Ehrlich, M. E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Fraser, P.] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [Fraser, P.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Westaway, D.; St George-Hyslop, P. H.] Univ Alberta, Ctr Prions & Prot Folding Dis, Edmonton, AB, Canada. [Szabo, P.; Relkin, N. R.; Petsko, G. A.] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. [Buxbaum, J. D.] Mt Sinai Sch Med, Dept Psychiat, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Buxbaum, J. D.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA. [Glabe, C. G.] Univ Calif Irvine, Dept Neurol, Sch Med, Irvine, CA 92717 USA. [Martins, R. N.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Crawley, WA, Australia. [Martins, R. N.] Hollywood Private Hosp, Sir James McCusker Alzheimers Dis Res Unit, Nedlands, WA, Australia. [Ehrlich, M. E.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Yue, Z.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Gandy, S.] James J Peters VA Med Ctr, Bronx, NY USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM samuel.gandy@mssm.edu RI Wang, Rong/A-8721-2009; OI Buxbaum, Joseph/0000-0001-8898-8313 FU National Institute of General Medical Sciences [T32GM062754]; Deutsche Forschungsgemeinschaft; Oligomer Research Consortium of the Cure Alzheimer's Fund; McCusker Alzheimer's Research Foundation; Conicyt [PFB-16]; Fidelity Biosciences Research Initiative; Cure Alzheimer's Fund; US Department of Veterans Affairs; NIH [P01AG10491, U01AG01483, NS045283, R01NS060123, U54RR022220, P30 NS061777, S10 RR022415, P50AG05138]; Canadian Institutes of Health Research and Alzheimer Society of Ontario; Baxter Healthcare FX The work in this manuscript was used in a dissertation by JWS as partial requirement for the fulfillment of the PhD degree. JWS is a trainee in the Integrated Pharmacological Sciences Training Program supported by grant T32GM062754 from the National Institute of General Medical Sciences. MLL was supported by the Deutsche Forschungsgemeinschaft. SG and CGG are members of the Oligomer Research Consortium of the Cure Alzheimer's Fund. We acknowledge the generous support of the NH&MRC (APP1009295 to RNM, GV, SG), the McCusker Alzheimer's Research Foundation (RNM, GV), Conicyt (PFB-16 to SB), the Fidelity Biosciences Research Initiative (SJ, JL, DR, GAP), Cure Alzheimer's Fund (SG; CGG), the US Department of Veterans Affairs (SG), the NIH (P01AG10491 to SG; U01AG01483 to PS; NS045283 to CGG, R01NS060123; U54RR022220 to ZY; P30 NS061777 and S10 RR022415 to RW; and P50AG05138 to Mary Sano), the Canadian Institutes of Health Research and Alzheimer Society of Ontario (PF), and Baxter Healthcare (PS and NRR). We would also like to thank Rosilyn Kazanjian for the gift in memory of Powel Kazanjian that supported the purchase of the Luminex xMAP100/200 system. We would like to thank Loren E Khan and Justine Bonet for technical assistance in animal colony management and Dr Yun Zhong for technical support. NR 35 TC 34 Z9 35 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD AUG PY 2013 VL 18 IS 8 BP 889 EP 897 DI 10.1038/mp.2012.106 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 191XM UT WOS:000322448400010 PM 22850627 ER PT J AU Rueckert, EH Barker, D Ruderfer, D Bergen, SE O'Dushlaine, C Luce, CJ Sheridan, SD Theriault, KM Chambert, K Moran, J Purcell, SM Madison, JM Haggarty, SJ Sklar, P AF Rueckert, E. H. Barker, D. Ruderfer, D. Bergen, S. E. O'Dushlaine, C. Luce, C. J. Sheridan, S. D. Theriault, K. M. Chambert, K. Moran, J. Purcell, S. M. Madison, J. M. Haggarty, S. J. Sklar, P. TI Cis-acting regulation of brain-specific ANK3 gene expression by a genetic variant associated with bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE ANK3; Ankyrin-G (AnkG); axon initial segment; bipolar disorder; human neurons; stem cells ID AXON INITIAL SEGMENT; GENOME-WIDE ASSOCIATION; ANKYRIN-G; RISK VARIANT; CACNA1C; CHANNELS; RANVIER; PROTEIN AB Several genome-wide association studies for bipolar disorder (BD) have found a strong association of the Ankyrin 3 (ANK3) gene. This association spans numerous linked single-nucleotide polymorphisms (SNPs) in an similar to 250-kb genomic region overlapping ANK3. The associated region encompasses predicted regulatory elements as well as two of the six validated alternative first exons, which encode distinct protein domains at the N-terminus of the protein also known as Ankyrin-G. Using RNA ligase-mediated rapid amplification of cDNA ends to identify novel transcripts in conjunction with a highly sensitive, exon-specific multiplexed mRNA expression assay, we detected differential regulation of distinct ANK3 transcription start sites and coupling of specific 5' ends with 3' mRNA splicing events in postmortem human brain and human stem cell-derived neural progenitors and neurons. Furthermore, allelic variation at the BD-associated SNP rs1938526 correlated with a significant difference in cerebellar expression of a brain-specific ANK3 transcript. These findings suggest a brain-specific cis-regulatory transcriptional effect of ANK3 that may be relevant to BD pathophysiology. C1 [Rueckert, E. H.; Ruderfer, D.; Bergen, S. E.; Purcell, S. M.; Haggarty, S. J.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet, Boston, MA 02114 USA. [Rueckert, E. H.; Ruderfer, D.; Bergen, S. E.; Purcell, S. M.; Haggarty, S. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rueckert, E. H.; Barker, D.; Ruderfer, D.; Bergen, S. E.; O'Dushlaine, C.; Luce, C. J.; Chambert, K.; Moran, J.; Purcell, S. M.; Madison, J. M.; Haggarty, S. J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Ruderfer, D.; Purcell, S. M.] Massachusetts Gen Hosp, Analyt Translat Genet Unit, Boston, MA 02114 USA. [Ruderfer, D.; Purcell, S. M.; Sklar, P.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Sheridan, S. D.; Theriault, K. M.; Haggarty, S. J.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Rueckert, E. H.; Sheridan, S. D.; Theriault, K. M.; Haggarty, S. J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Sklar, P (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM haggarty@chgr.mgh.harvard.edu; pamela.sklar@mssm.edu RI Ruderfer, Douglas/M-5795-2016; OI Ruderfer, Douglas/0000-0002-2365-386X; Bergen, Sarah/0000-0002-5888-0034; Moran, Jennifer/0000-0002-5664-4716; Haggarty, Stephen J./0000-0002-7872-168X FU Stanley Medical Research Institute; National Institute Of Mental Health [R33MH087896] FX We gratefully acknowledge the Stanley Medical Research Institute (Maree Webster) for providing RNA and tissue samples from their postmortem human brain collection and the Massachusetts General Hospital Brain Bank (Charles Vanderburg) for generously providing postmortem human brain samples. Funding was provided by the Stanley Medical Research Institute and from the National Institute Of Mental Health (R33MH087896). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of Mental Health or the National Institutes of Health. We thank Drs Tracey Petryshen and Melanie Leussis for ongoing discussions and helpful review of this manuscript, and Leslie Gaffney for editorial assistance in preparing the figures for publication. NR 36 TC 21 Z9 21 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD AUG PY 2013 VL 18 IS 8 BP 922 EP 929 DI 10.1038/mp.2012.104 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 191XM UT WOS:000322448400014 PM 22850628 ER PT J AU Logue, MW Baldwin, C Guffanti, G Melista, E Wolf, EJ Reardon, AF Uddin, M Wildman, D Galea, S Koenen, KC Miller, MW AF Logue, M. W. Baldwin, C. Guffanti, G. Melista, E. Wolf, E. J. Reardon, A. F. Uddin, M. Wildman, D. Galea, S. Koenen, K. C. Miller, M. W. TI A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus SO MOLECULAR PSYCHIATRY LA English DT Article DE genome-wide association; post-traumatic stress disorder; RORA ID MULTILOCUS GENOTYPE DATA; TRAUMA EXPOSURE; PTSD; COMORBIDITY; DEPRESSION; SCAN; VISUALIZATION; METAANALYSIS; PERSONALITY; INFERENCE AB We describe the results of the first genome-wide association study (GWAS) of post-traumatic stress disorder (PTSD) performed using trauma-exposed white non-Hispanic participants from a cohort of veterans and their intimate partners (295 cases and 196 controls). Several single-nucleotide polymorphisms (SNPs) yielded evidence of association. One SNP (rs8042149), located in the retinoid-related orphan receptor alpha gene (RORA), reached genome-wide significance. Nominally significant associations were observed for other RORA SNPs in two African-American replication samples-one from the veteran cohort (43 cases and 41 controls) and another independent cohort (100 cases and 421 controls). However, only the associated SNP from the veteran African-American replication sample survived gene-level multiple-testing correction. RORA has been implicated in prior GWAS studies of psychiatric disorders and is known to have an important role in neuroprotection and other behaviorally relevant processes. This study represents an important step toward identifying the genetic underpinnings of PTSD. C1 [Logue, M. W.; Baldwin, C.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Logue, M. W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Baldwin, C.; Melista, E.] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. [Guffanti, G.] Columbia Univ, Dept Psychiat, NYSPI, Div Child & Adolescent Psychiat, New York, NY USA. [Wolf, E. J.; Reardon, A. F.; Miller, M. W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, E. J.; Miller, M. W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Uddin, M.; Wildman, D.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Uddin, M.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Sch Med, Detroit, MI 48207 USA. [Wildman, D.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Galea, S.; Koenen, K. C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; Koenen, Karestan/K-5402-2014; OI Miller, Mark/0000-0001-6393-8563; Logue, Mark/0000-0001-9347-7892; Koenen, Karestan/0000-0003-3293-4281; Wolf, Erika/0000-0003-2666-2435 FU National Institute on Mental Health [RO1 MH079806, K01 MH076100]; Department of Veterans Affairs; [DA022720]; [DA022720-S1]; [MH088283.]; [MH093612]; [MH078928]; [P51RR000165] FX Funding for this study was provided by National Institute on Mental Health award RO1 MH079806 and a Department of Veterans Affairs Merit Review Grant awarded to MWM. MWL is funded by National Institute on Mental Health award K01 MH076100. The Detroit Neighborhood Health Study (PI: Allison Aiello) is funded by DA022720, DA022720-S1 and MH088283. KCK is funded by MH093612, MH078928, P51RR000165 NR 44 TC 60 Z9 61 U1 1 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD AUG PY 2013 VL 18 IS 8 BP 937 EP 942 DI 10.1038/mp.2012.113 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 191XM UT WOS:000322448400016 PM 22869035 ER PT J AU Maguire, CA Crommentuijn, MHW Mu, DK Hudry, E Serrano-Pozo, A Hyman, BT Tannous, BA AF Maguire, Casey A. Crommentuijn, Matheus H. W. Mu, Dakai Hudry, Eloise Serrano-Pozo, Alberto Hyman, Bradley T. Tannous, Bakhos A. TI Mouse Gender Influences Brain Transduction by Intravascularly Administered AAV9 SO MOLECULAR THERAPY LA English DT Letter ID ADENOASSOCIATED VIRAL VECTORS; GENE-TRANSFER SUPERIOR; SPINAL-CORD; DELIVERY; NEURONS; MICE; SEROTYPE; LIVER; ASTROCYTES; TISSUES C1 [Maguire, Casey A.; Crommentuijn, Matheus H. W.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Maguire, Casey A.; Crommentuijn, Matheus H. W.; Mu, Dakai; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Crommentuijn, Matheus H. W.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp,Dept Neurosurg, Amsterdam, Netherlands. [Hudry, Eloise; Serrano-Pozo, Alberto; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. EM btannous@hms.harvard.edu NR 15 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD AUG PY 2013 VL 21 IS 8 BP 1469 EP 1470 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 193RG UT WOS:000322578600003 ER PT J AU Amin, MN McLellan, JS Huang, W Orwenyo, J Burton, DR Koff, WC Kwong, PD Wang, LX AF Amin, Mohammed N. McLellan, Jason S. Huang, Wei Orwenyo, Jared Burton, Dennis R. Koff, Wayne C. Kwong, Peter D. Wang, Lai-Xi TI Synthetic glycopeptides reveal the glycan specificity of HIV-neutralizing antibodies SO NATURE CHEMICAL BIOLOGY LA English DT Article ID BETA-N-ACETYLGLUCOSAMINIDASE; CHEMOENZYMATIC SYNTHESIS; TRANSGLYCOSYLATION ACTIVITY; GLYCOSYLATION; GLYCOPROTEINS; POTENT; BROAD; RECOGNITION; OXAZOLINES; DOMAIN AB A new class of glycan-reactive HIV-neutralizing antibodies, including PG9 and PG16, has been recently discovered that seem to recognize previously uncharacterized glycopeptide epitopes on HIV-1 gp120. However, further characterization and reconstitution of the precise neutralizing epitopes are complicated by the heterogeneity of glycosylation. We report here the design, synthesis and antigenic evaluation of new cyclic V1V2 glycopeptides carrying defined N-linked glycans at the conserved glycosylation sites (Asn160 and Asn156 or Asn173) derived from gp120 of two HIV-1 isolates. Antibody binding studies confirmed the necessity of a Man(5)GlcNAc(2) glycan at Asn160 for recognition by PG9 and PG16 and further revealed a critical role of a sialylated N-glycan at the secondary site (Asn156 or Asn173) in the context of glycopeptides for antibody binding. In addition to defining the glycan specificities of PG9 and PG16, the identified synthetic glycopeptides provide a valuable template for HIV-1 vaccine design. C1 [Amin, Mohammed N.; Huang, Wei; Orwenyo, Jared; Wang, Lai-Xi] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Amin, Mohammed N.; Huang, Wei; Orwenyo, Jared; Wang, Lai-Xi] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [McLellan, Jason S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat IAVI, Neutralizing Antibody Ctr, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, Massachusetts Inst Technol & Harvard, Ragon Inst, Cambridge, MA USA. [Koff, Wayne C.] IAVI, New York, NY USA. RP Wang, LX (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. EM LWang@som.umaryland.edu FU National Institute of Allergy and Infectious Diseases (NIAID) (US National Institutes of Health (NIH) [1R21AI101035]; International AIDS Vaccine Initiative's Neutralizing Antibody Consortium; Intramural Research Program of the Vaccine Research Center, NIAID-NIH FX We thank S. Fan (University of Maryland) for providing the recombinant Endo-D and K. Moremen and Y. Xiang (University of Georgia) for providing the recombinant mouse alpha-1,2-mannosidase. This work is supported in parts by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (US National Institutes of Health (NIH) grant 1R21AI101035 to L.-X. W.), the International AIDS Vaccine Initiative's Neutralizing Antibody Consortium and by the Intramural Research Program of the Vaccine Research Center, NIAID-NIH. NR 42 TC 43 Z9 44 U1 3 U2 60 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD AUG PY 2013 VL 9 IS 8 BP 521 EP 526 DI 10.1038/nchembio.1288 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185FV UT WOS:000321952700012 PM 23831758 ER PT J AU Samuel, A Levine, H Blagoev, KB AF Samuel, Aravi Levine, Herbert Blagoev, Krastan B. TI Scientific priorities for the BRAIN Initiative SO NATURE METHODS LA English DT Article ID ACTIVITY MAP; DYNAMICS; SYSTEM C1 [Samuel, Aravi] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Samuel, Aravi] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Levine, Herbert] Rice Univ, Dept Bioengn, Houston, TX USA. [Blagoev, Krastan B.] Natl Sci Fdn, Arlington, VA USA. [Blagoev, Krastan B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Blagoev, Krastan B.] Harvard Univ, Sch Med, Boston, MA USA. [Blagoev, Krastan B.] Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Samuel, A (reprint author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. EM kblagoev@nsf.gov RI Levine, Herbert/C-1704-2008 OI Levine, Herbert/0000-0002-8819-9055 NR 9 TC 2 Z9 2 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD AUG PY 2013 VL 10 IS 8 BP 713 EP 714 DI 10.1038/nmeth.2565 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 191ZL UT WOS:000322453600016 PM 23900253 ER PT J AU Plenge, RM Scolnick, EM Altshuler, D AF Plenge, Robert M. Scolnick, Edward M. Altshuler, David TI Validating therapeutic targets through human genetics SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; SPINAL MUSCULAR-ATROPHY; RESEARCH-AND-DEVELOPMENT; HUTCHINSON-GILFORD PROGERIA; TRANSFER PROTEIN-INHIBITION; INFLAMMATORY-BOWEL-DISEASE; CORONARY-HEART-DISEASE; EXTREME PAIN DISORDER; RHEUMATOID-ARTHRITIS AB More than 90% of the compounds that enter clinical trials fail to demonstrate sufficient safety and efficacy to gain regulatory approval. Most of this failure is due to the limited predictive value of preclinical models of disease, and our continued ignorance regarding the consequences of perturbing specific targets over long periods of time in humans. 'Experiments of nature' - naturally occurring mutations in humans that affect the activity of a particular protein target or targets - can be used to estimate the probable efficacy and toxicity of a drug targeting such proteins, as well as to establish causal rather than reactive relationships between targets and outcomes. Here, we describe the concept of dose-response curves derived from experiments of nature, with an emphasis on human genetics as a valuable tool to prioritize molecular targets in drug development. We discuss empirical examples of drug-gene pairs that support the role of human genetics in testing therapeutic hypotheses at the stage of target validation, provide objective criteria to prioritize genetic findings for future drug discovery efforts and highlight the limitations of a target validation approach that is anchored in human genetics. C1 [Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Plenge, Robert M.; Scolnick, Edward M.; Altshuler, David] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Scolnick, Edward M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol & Diabet Unit, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. RP Plenge, RM (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. EM rplenge@partners.org RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 111 TC 136 Z9 138 U1 5 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD AUG PY 2013 VL 12 IS 8 BP 581 EP 594 DI 10.1038/nrd4051 PG 14 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 193QQ UT WOS:000322576700017 PM 23868113 ER PT J AU Alexander, BM Wen, PY Trippa, L Reardon, DA Yung, WKA Parmigiani, G Berry, DA AF Alexander, Brian M. Wen, Patrick Y. Trippa, Lorenzo Reardon, David A. Yung, Wai-Kwan Alfred Parmigiani, Giovanni Berry, Donald A. TI Biomarker-based adaptive trials for patients With glioblastoma-lessons from I-SPY 2 SO NEURO-ONCOLOGY LA English DT Article DE adaptive; Bayesian; biomarker; clinical trials; glioblastoma ID PROGRESSION-FREE SURVIVAL; INTEGRATED GENOMIC ANALYSIS; HIGH-GRADE GLIOMAS; CLINICAL-TRIALS; PHASE-II; RECURRENT GLIOBLASTOMA; WORKING GROUP; END-POINT; TEMOZOLOMIDE; DESIGN AB The traditional clinical trials infrastructure may not be ideally suited to evaluate the numerous therapeutic hypotheses that result from the increasing number of available targeted agents combined with the various methodologies to molecularly subclassify patients with glioblastoma. Additionally, results from smaller screening studies are rarely translated to successful larger confirmatory studies, potentially related to a lack of efficient control arms or the use of unvalidated surrogate end-points. Streamlining clinical trials and providing a flexible infrastructure for biomarker development is clearly needed for patients with glioblastoma. The experience developing and implementing the I-SPY studies in breast cancer may serve as a guide to developing such trials in neuro-oncology. C1 [Alexander, Brian M.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Alexander, Brian M.; Wen, Patrick Y.; Reardon, David A.] Harvard Univ, Sch Med, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Trippa, Lorenzo; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Yung, Wai-Kwan Alfred] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 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 NCI NIH HHS [P30 CA016672] NR 46 TC 10 Z9 10 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2013 VL 15 IS 8 BP 972 EP 978 DI 10.1093/neuonc/not088 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 191PV UT WOS:000322426000002 PM 23857706 ER PT J AU Lu-Emerson, C Snuderl, M Kirkpatrick, ND Goveia, J Davidson, C Huang, YH Riedemann, L Taylor, J Ivy, P Duda, DG Ancukiewicz, M Plotkin, SR Chi, AS Gerstner, ER Eichler, AF Dietrich, J Stemmer-Rachamimov, AO Batchelor, TT Jain, RK AF Lu-Emerson, Christine Snuderl, Matija Kirkpatrick, Nathaniel D. Goveia, Jermaine Davidson, Christian Huang, Yuhui Riedemann, Lars Taylor, Jennie Ivy, Percy Duda, Dan G. Ancukiewicz, Marek Plotkin, Scott R. Chi, Andrew S. Gerstner, Elizabeth R. Eichler, April F. Dietrich, Jorg Stemmer-Rachamimov, Anat O. Batchelor, Tracy T. Jain, Rakesh K. TI Increase in tumor-associated macrophages after antiangiogenic therapy is associated with poor survival among patients with recurrent glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE antiangiogenic therapy; glioblastoma; myeloid cells; relapse ID ANTI-VEGF THERAPY; HUMAN GLIOMAS; CLINICAL-TRIALS; BEVACIZUMAB; PROGRESSION; INFILTRATION; METASTASIS; GROWTH; CANCER; CELLS AB Antiangiogenic therapy is associated with increased radiographic responses in glioblastomas, but tumors invariably recur. Because tumor-associated macrophages have been shown to mediate escape from antiangiogenic therapy in preclinical models, we examined the role of macrophages in patients with recurrent glioblastoma. We compared autopsy brain specimens from 20 patients with recurrent glioblastoma who received antiangiogenic treatment and chemoradiation with 8 patients who received chemotherapy and/or radiotherapy without antiangiogenic therapy or no treatment. Tumor-associated macrophages were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in macrophages in the antiangiogenic-treated patients. Immunohistochemical analysis demonstrated an increase in CD68+ macrophages in the tumor bulk (P < .01) and infiltrative areas (P = .02) in antiangiogenic-treated patients. We also observed an increase in CD11b+ cells in the tumor bulk (P < .01) and an increase in CD163+ macrophages in infiltrative tumor (P = .02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumors (P = .05 and P = .05, respectively) correlated with poor overall survival among patients who first received antiangiogenic therapy at recurrence. In summary, recurrent glioblastomas showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after antiangiogenic therapy. Higher numbers of CD11b+ cells correlated with poor survival among these patients. These data suggest that tumor-associated macrophages may participate in escape from antiangiogenic therapy and may represent a potential biomarker of resistance and a potential therapeutic target in recurrent glioblastoma. C1 [Lu-Emerson, Christine; Taylor, Jennie; Plotkin, Scott R.; Chi, Andrew S.; Gerstner, Elizabeth R.; Eichler, April F.; Dietrich, Jorg; Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Ctr Canc, Boston, MA 02114 USA. [Snuderl, Matija; Davidson, Christian; Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Boston, MA 02114 USA. [Kirkpatrick, Nathaniel D.; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Duda, Dan G.; Ancukiewicz, Marek; Jain, Rakesh K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kirkpatrick, Nathaniel D.; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Duda, Dan G.; Ancukiewicz, Marek; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Steele Lab, COX 734,100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Riedemann, Lars/J-5725-2014; OI Riedemann, Lars/0000-0002-9510-1845; Huang, Yuhui/0000-0003-1985-3575; Snuderl, Matija/0000-0003-0752-0917 FU National Foundation for Cancer Research; National Institutes of Health [R01CA129371, U01CA062490, K24CA 125440A, P01CA080124, R01CA163815, R01CA159258]; Proton Beam/Federal Share Program; Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health ) [8UL1TR000170-05]; Harvard University FX This work was funded by a the National Foundation for Cancer Research grant (to R.K.J.), the National Institutes of Health (grants R01CA129371, U01CA062490, K24CA 125440A to T.T.B.; P01CA080124, R01CA163815 to R.K.J.; R01CA159258 to D.G.D.); Proton Beam/Federal Share Program (to R.K.J. and D.G.D.), and the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). NR 36 TC 36 Z9 36 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2013 VL 15 IS 8 BP 1079 EP 1087 DI 10.1093/neuonc/not082 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 191PV UT WOS:000322426000014 PM 23828240 ER PT J AU Liu, S Ren, JA Li, JS AF Liu, Song Ren, Jianan Li, Jieshou TI Response: Efficacy of Erythropoietin Combined With Enteral Nutrition for the Treatment of Anemia in Crohn's Disease SO NUTRITION IN CLINICAL PRACTICE LA English DT Letter C1 [Liu, Song; Ren, Jianan; Li, Jieshou] Nanjing Univ, Sch Med, Jinling Hosp, Dept Gen Surg, Nanjing 210008, Jiangsu, Peoples R China. [Liu, Song] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Liu, Song] Harvard Univ, Sch Med, Boston, MA USA. RP Liu, S (reprint author), Nanjing Univ, Sch Med, Jinling Hosp, Dept Gen Surg, Nanjing 210008, Jiangsu, Peoples R China. OI LIU, SONG/0000-0002-4780-9697; Ren, Jianan/0000-0002-7978-8093 NR 7 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 0884-5336 J9 NUTR CLIN PRACT JI Nutr. Clin. Pract. PD AUG PY 2013 VL 28 IS 4 BP 523 EP 523 DI 10.1177/0884533613487220 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 196JU UT WOS:000322771600015 PM 23736687 ER PT J AU Hall, SRR Jiang, YJ Leary, E Yavanian, G Eminli, S O'Neill, DW Marasco, WA AF Hall, Sean R. R. Jiang, Yajuan Leary, Elizabeth Yavanian, Greg Eminli, Sarah O'Neill, David W. Marasco, Wayne A. TI Identification and Isolation of Small CD44-Negative Mesenchymal Stem/Progenitor Cells From Human Bone Marrow Using Elutriation and Polychromatic Flow Cytometry SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE CD44; Elutriation; FACS; Mesenchymal progenitor cells; Bone marrow ID ADULT STEM-CELLS; STROMAL CELLS; CENTRIFUGAL ELUTRIATION; PROGENITOR CELLS; IN-VIVO; PRECURSORS; CD44; LEUKAPHERESIS; ENGRAFTMENT; ENRICHMENT AB The method of isolation of bone marrow (BM) mesenchymal stem/stromal cells (MSCs) is a limiting factor in their study and therapeutic use. MSCs are typically expanded from BM cells selected on the basis of their adherence to plastic, which results in a heterogeneous population of cells. Prospective identification of the antigenic profile of the MSC population(s) in BM that gives rise to cells with MSC activity in vitro would allow the preparation of very pure populations of MSCs for research or clinical use. To address this issue, we used polychromatic flow cytometry and counterflow centrifugal elutriation to identify a phenotypically distinct population of mesenchymal stem/progenitor cells (MSPCs) within human BM. The MSPC activity resided within a population of rare, small CD45(-)CD73(+)CD90(+)CD105(+) cells that lack CD44, an antigen that is highly expressed on culture-expanded MSCs. In culture, these MSPCs adhere to plastic, rapidly proliferate, and acquire CD44 expression. They form colony forming units-fibroblast and are able to differentiate into osteoblasts, chondrocytes, and adipocytes under defined in vitro conditions. Their acquired expression of CD44 can be partially downregulated by treatment with recombinant human granulocyte-colony stimulating factor, a response not found in BM-MSCs derived from conventional plastic adherence methods. These observations indicate that MSPCs within human BM are rare, small CD45(-)CD73(+)CD90(+)CD105(+) cells that lack expression of CD44. These MSPCs give rise to MSCs that have phenotypic and functional properties that are distinct from those of BM-MSCs purified by plastic adherence. C1 [Hall, Sean R. R.; Jiang, Yajuan; Leary, Elizabeth; Yavanian, Greg; Eminli, Sarah; O'Neill, David W.] NeoStem Inc, Cambridge, MA USA. [Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP O'Neill, DW (reprint author), NeoStem Inc, 420 Lexington Ave,Suite 450, New York, NY 10170 USA. EM doneill@progenitorcell.net; wayne_marasco@dfci.harvard.edu FU NeoStem, Inc. FX We thank Anthony Salerno for his enthusiastic support of this work. This study was funded by NeoStem, Inc. NR 53 TC 7 Z9 10 U1 0 U2 13 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD AUG PY 2013 VL 2 IS 8 BP 567 EP 578 DI 10.5966/sctm.2012-0155 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 195DK UT WOS:000322682300003 PM 23847000 ER PT J AU Schwaitzberg, SD Hawes, RH Rattner, DW Kochman, ML AF Schwaitzberg, Steven D. Hawes, Robert H. Rattner, David W. Kochman, Michael L. TI Novel challenges of multi-society investigator-initiated studies: a paradigm shift for technique and technology evaluation SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Review DE NOTES; Natural orifice; Comparative effectiveness; Conflict of interest; cholecystectomy AB The introduction of innovative techniques and novel technologies into clinical practice is a challenge that confronts all aspects of healthcare delivery. Upheaval from shrinking research funding and declining healthcare reimbursements now forces patients, doctors, hospitals, payers, regulators, and even health systems into conflict as new therapies struggle to find a place in the therapeutic armamentarium. The escalating costs of healthcare force all parties to consider both the medical risks/benefits as well as the economic efficiency of proposed tools and therapies. We highlight these challenges by examining the process of initiating and conducting a "society-as-investigator" clinical trial to assess the safety of the natural orifice translumenal endoscopic surgery (NOTES) approach to cholecystectomy in the context of the issues that confront technology diffusion today. C1 [Schwaitzberg, Steven D.] Cambridge Hlth Alliance, Dept Surg, Cambridge, MA 02139 USA. [Hawes, Robert H.] Florida Hosp, Orlando, FL USA. [Rattner, David W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kochman, Michael L.] Univ Penn Hlth Syst, Div Gastroenterol, Philadelphia, PA USA. RP Schwaitzberg, SD (reprint author), Cambridge Hlth Alliance, Dept Surg, 1493 Cambridge St, Cambridge, MA 02139 USA. EM sschwaitzberg@challiance.org NR 10 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD AUG PY 2013 VL 27 IS 8 BP 2673 EP 2677 DI 10.1007/s00464-012-2504-0 PG 5 WC Surgery SC Surgery GA 185IS UT WOS:000321961700003 PM 23754451 ER PT J AU Clarke, MSF Sundaresan, A Vanderburg, CR Banigan, MG Pellis, NR AF Clarke, Mark S. F. Sundaresan, Alamelu Vanderburg, Charles R. Banigan, Meredith G. Pellis, Neal R. TI A three-dimensional tissue culture model of bone formation utilizing rotational co-culture of human adult osteoblasts and osteoclasts SO ACTA BIOMATERIALIA LA English DT Article DE Bone; Rotational culture; Bone progenitor cells; SOST; BMP ID GENE-EXPRESSION; DIFFERENTIATION; CELLS; MINERALIZATION; PROLIFERATION; OSTEOPOROSIS; PATHOGENESIS; RESORPTION; MATRIX; BETA AB Living bone is a complex, three-dimensional composite material consisting of numerous cell types spatially organized within a mineralized extracellular matrix. To date, mechanistic investigation of the complex cellular level cross-talk between the major bone-forming cells involved in the response of bone to mechanical and biochemical stimuli has been hindered by the lack of a suitable in vitro model that captures the "coupled" nature of this response. Using a novel rotational co-culture approach, we have generated large (>4 mm diameter), three-dimensional mineralized tissue constructs from a mixture of normal human primary osteoblast and osteoclast precursor cells without the need for any exogenous osteoconductive scaffolding material that might interfere with such cell-cell interactions. Mature, differentiated bone constructs consist of an outer region inhabited by osteoclasts and osteoblasts and a central region containing osteocytes encased in a self-assembled, porous mineralized extracellular matrix. Bone constructs exhibit morphological, mineral and biochemical features similar to remodeling human trabecular bone, including the expression of mRNA for SOST, BGLAP, ACP5, BMP-2, BMP-4 and BMP-7 within the construct and the secretion of BMP-2 protein into the medium. This "coupled" model of bone formation will allow the future investigation of various stimuli on the process of normal bone formation/remodeling as it relates to the cellular function of osteoblasts, osteoclasts and osteocytes in the generation of human mineralized tissue. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Clarke, Mark S. F.] Univ Houston, Dept Hlth & Human Performance, Houston, TX 77204 USA. [Sundaresan, Alamelu] Texas So Univ, Dept Biol, Houston, TX 77204 USA. [Vanderburg, Charles R.; Banigan, Meredith G.] Massachusetts Gen Hosp, Harvard NeuroDiscovety Ctr, Boston, MA 02114 USA. [Pellis, Neal R.] Univ Space Res Assoc, Div Space Life Sci, Houston, TX 77058 USA. RP Clarke, MSF (reprint author), Univ Houston, Dept Hlth & Human Performance, Garrison Bldg,Room 104,3855 Holman St, Houston, TX 77204 USA. EM mclarke@central.uh.edu FU Center Director's Discretionary Fund (CDDF) at NASA-Johnson Space Center FX This work was supported by a research grant from the Center Director's Discretionary Fund (CDDF) at NASA-Johnson Space Center awarded to M.S.F.C. and A.S. NR 36 TC 6 Z9 8 U1 5 U2 27 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD AUG PY 2013 VL 9 IS 8 BP 7908 EP 7916 DI 10.1016/j.actbio.2013.04.051 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 188QD UT WOS:000322207700031 PM 23664885 ER PT J AU Crabbe, JC Spence, SE Huang, LC Cameron, AJ Schlumbohm, JP Barkley-Levenson, AM Metten, P AF Crabbe, John C. Spence, Stephanie E. Huang, Lawrence C. Cameron, Andy J. Schlumbohm, Jason P. Barkley-Levenson, Amanda M. Metten, Pamela TI Ethanol drinking in Withdrawal Seizure-Prone and -Resistant selected mouse lines SO ALCOHOL LA English DT Article DE Ethanol withdrawal; Selective breeding; Ethanol preference; Drinking in the dark; Mouse; Genetics ID ACUTE ALCOHOL-WITHDRAWAL; QUANTITATIVE TRAIT LOCI; STRAIN DIFFERENCES; MUS-MUSCULUS; INBRED MICE; RAT LINES; SEVERITY; PREFERENCE; SUSCEPTIBILITY; INTOXICATION AB Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mouse lines were bidirectionally selectively bred, respectively, to have severe or mild ethanol withdrawal handling-induced convulsions (HICs) after cessation of 3 days of ethanol vapor inhalation. Murine genotypes with severe withdrawal have been found to show low ethanol consumption, and high consumers show low withdrawal. An early drinking study with WSP and WSR mice showed modest evidence consistent with this genetic correlation, but there were several limitations to that experiment. We therefore conducted a thorough assessment of two bottle ethanol preference drinking in both replicate pairs of WSP/WSR selected lines in mice of both sexes. Greater preference drinking of WSR-2 than WSP-2 female mice confirmed the earlier report. However, in the parallel set of selected lines, the WSP-1 mice drank more than the WSR-1s. Naive mice tested for preference for sucrose, saccharin and quinine did not differ markedly for any tastant Finally, in a test of binge-like drinking, Drinking in the Dark (DID), WSP mice drank more than WSR mice and attained significantly higher (but still modest) blood ethanol concentrations. Tests of acute withdrawal after DID showed a mild, but significant elevation in handling-induced convulsions in the WSP line. These results provide further evidence that 2-bottle ethanol preference and DID are genetically distinguishable traits. Published by Elsevier Inc. C1 [Crabbe, John C.; Spence, Stephanie E.; Huang, Lawrence C.; Cameron, Andy J.; Schlumbohm, Jason P.; Barkley-Levenson, Amanda M.; Metten, Pamela] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. [Crabbe, John C.; Spence, Stephanie E.; Huang, Lawrence C.; Cameron, Andy J.; Schlumbohm, Jason P.; Barkley-Levenson, Amanda M.; Metten, Pamela] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Crabbe, JC (reprint author), Portland VA Med Ctr, Res R&D 12,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM crabbe@ohsu.edu FU NIH-NIAAA [AA10760, AA13519, AA20245, AA007468]; Department of Veterans Affairs; Department of the Army/DoD-TATRC grant [10245005.05]; Achievement Rewards for College Scientists Foundation; OHSU Graduate Research Scholar fellowship FX These studies were supported by Grants AA10760, AA13519, and AA20245 from the NIH-NIAAA; by the Department of Veterans Affairs; and by the Department of the Army/DoD-TATRC grant 10245005.05. AMB-L was supported by NIH-NIAAA grant AA007468, the Achievement Rewards for College Scientists Foundation, and an OHSU Graduate Research Scholar fellowship. NR 29 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD AUG PY 2013 VL 47 IS 5 BP 381 EP 389 DI 10.1016/j.alcohol.2013.05.002 PG 9 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 187EH UT WOS:000322099200004 PM 23809872 ER PT J AU McCarthy, MJ Fernandes, M Kranzler, HR Covault, JM Welsh, DK AF McCarthy, Michael J. Fernandes, Malcolm Kranzler, Henry R. Covault, Jonathan M. Welsh, David K. TI Circadian Clock Period Inversely Correlates with Illness Severity in Cells from Patients with Alcohol Use Disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Circadian Rhythm; Genetics; Alcohol ID GENE-EXPRESSION; ACTIVITY RHYTHMS; BETA-ENDORPHIN; FAMILY-HISTORY; SLEEP PROBLEMS; CONSUMPTION; ETHANOL; DEPENDENCE; RELAPSE; RATS AB Background: Clinical and genetic studies suggest circadian clock genes may contribute to biological mechanisms underlying alcohol use disorders (AUD). In particular, the Per2 gene regulates alcohol consumption in mutant animals, and in humans with AUD, the 10870 variant in PER2 has been associated with alcohol consumption. However, with respect to function, the molecular clock remains largely uncharacterized in AUD patients. Methods: In skin fibroblast cultures from well-characterized human AUD patients (n = 19) and controls (n = 13), we used a bioluminescent reporter gene (Per2:: luc) to measure circadian rhythms in gene expression at high sampling density for 5 days. Cells were genotyped for the PER2 10870 variant. The rhythm parameters period and amplitude were then analyzed using a case-control design and by genetic and clinical characteristics of the AUD subjects. Results: There were no differences between AUD cases and controls in rhythm parameters. However, period was inversely correlated with illness severity (defined as the number of alcohol dependence criteria met). The PER2 variant 10870 was not associated with differences in rhythm parameters. Conclusions: Our data suggest that differences in the cellular circadian clock are not pronounced in fibroblasts from AUD cases and controls. However, we found evidence that the circadian clock may be associated with an altered trajectory of AUD, possibly related to illness severity. Future work will be required to determine the mechanistic basis of this association. C1 [McCarthy, Michael J.; Fernandes, Malcolm; Welsh, David K.] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. [McCarthy, Michael J.; Fernandes, Malcolm; Welsh, David K.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [McCarthy, Michael J.; Fernandes, Malcolm; Welsh, David K.] Univ Calif San Diego, Ctr Chronobiol, San Diego, CA 92103 USA. [Kranzler, Henry R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Covault, Jonathan M.] Univ Connecticut, Sch Med, Alcohol Res Ctr, Farmington, CT USA. RP McCarthy, MJ (reprint author), Vet Affairs San Diego Healthcare Syst, 3350 La Jolla Village Dr MC 116A, San Diego, CA 92161 USA. EM mmccarthy@ucsd.edu OI McCarthy, Michael/0000-0001-6219-4945 FU Veterans Affairs Career Development Award [1IK2BX001275]; NIH [R21AA017584, R01AA021164]; Veterans Affairs Merit Award [1I01BX001146]; NIMH [R01 MH082945]; NARSAD Young Investigator Award FX MJM is supported by a Veterans Affairs Career Development Award (1IK2BX001275). JMC receives support from NIH (R21AA017584). HRK receives support from NIH (R01AA021164). DKW receives support from a Veterans Affairs Merit Award (1I01BX001146), NIMH (R01 MH082945), and a NARSAD Young Investigator Award. The funders had no role in the analysis, decision to publish, or preparation of the manuscript. NR 40 TC 9 Z9 9 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2013 VL 37 IS 8 BP 1304 EP 1310 DI 10.1111/acer.12106 PG 7 WC Substance Abuse SC Substance Abuse GA 190GV UT WOS:000322328300008 PM 23550834 ER PT J AU Rubinsky, AD Dawson, DA Williams, EC Kivlahan, DR Bradley, KA AF Rubinsky, Anna D. Dawson, Deborah A. Williams, Emily C. Kivlahan, Daniel R. Bradley, Katharine A. TI AUDIT-C Scores as a Scaled Marker of Mean Daily Drinking, Alcohol Use Disorder Severity, and Probability of Alcohol Dependence in a US General Population Sample of Drinkers SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE AUDIT-C; Alcohol Screening; Mean Daily Drinking; Alcohol Misuse Severity; Alcohol Dependence ID NATIONAL EPIDEMIOLOGIC SURVEY; PRIMARY-CARE PATIENTS; RISK DRINKING; CONSUMPTION QUESTIONS; IDENTIFICATION TEST; UNITED-STATES; METAANALYSIS; INTERVENTION; VALIDITY; IV AB Background: Brief alcohol screening questionnaires are increasingly used to identify alcohol misuse in routine care, but clinicians also need to assess the level of consumption and the severity of misuse so that appropriate intervention can be offered. Information provided by a patient's alcohol screening score might provide a practical tool for assessing the level of consumption and severity of misuse. Methods: This post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U. S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria ("AUD severity"), and the probability of alcohol dependence associated with each individual AUDIT-C score (1 to 12), after testing for effect modification by gender and age. Results: Among eligible past-year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT-C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT-C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT-C scores among younger versus older age groups. Conclusions: Results of this study could be used to estimate patient-specific consumption and severity based on age, gender, and alcohol screening score. This information could be integrated into electronic decision support systems to help providers estimate and provide feedback about patient-specific risks and identify those patients most likely to benefit from further diagnostic assessment. C1 [Rubinsky, Anna D.; Williams, Emily C.; Kivlahan, Daniel R.; Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Rubinsky, Anna D.; Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Dawson, Deborah A.] NIAAA, Lab Epidemiol & Biometry, Div Clin & Biol Res, NIH, Bethesda, MD USA. [Dawson, Deborah A.] Kelly Govt Serv Inc, Bethesda, MD USA. [Kivlahan, Daniel R.; Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Rubinsky, AD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. EM anna.rubinsky@va.gov FU U.S. Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development; Substance Use Disorders Quality Enhancement Research Initiative; Agency for Healthcare Research and Quality (AHRQ) National Research Services Award (NRSA) at the University of Washington [T32 HS013853] FX The research reported here was supported by the U.S. Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development, and the Substance Use Disorders Quality Enhancement Research Initiative. ADR was also supported by an Agency for Healthcare Research and Quality (AHRQ) National Research Services Award (NRSA) at the University of Washington (T32 HS013853). 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, the United States Government, or any of the authors' institutions. NR 49 TC 36 Z9 36 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2013 VL 37 IS 8 BP 1380 EP 1390 DI 10.1111/acer.12092 PG 11 WC Substance Abuse SC Substance Abuse GA 190GV UT WOS:000322328300017 PM 23906469 ER PT J AU Ngo, AVH Walker, CM Chung, JH Takasugi, JE Stern, EJ Kanne, JP Reddy, GP Godwin, JD AF Ngo, Anh-Vu H. Walker, Christopher Michael Chung, Jonathan H. Takasugi, Julie E. Stern, Eric J. Kanne, Jeffrey P. Reddy, Gautham P. Godwin, J. David TI Tumors and Tumorlike Conditions of the Large Airways SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE bronchial mass; large-airway abnormality; tracheal mass ID RECURRENT RESPIRATORY PAPILLOMATOSIS; RADIOLOGIC-PATHOLOGICAL CORRELATION; HUMAN PAPILLOMAVIRUS-11 DNA; SQUAMOUS-CELL CARCINOMA; FOREIGN-BODY ASPIRATION; MUCOEPIDERMOID CARCINOMA; BRONCHOGENIC-CARCINOMA; TRACHEOBRONCHIAL TREE; MULTIDETECTOR CT; WEGENERS-GRANULOMATOSIS AB OBJECTIVE. Large-airway tumors and tumorlike conditions are uncommon, but a systematic approach aids in narrowing the differential diagnosis. In this article, we describe an approach to dealing with large-airway lesions and discuss their imaging characteristics and clinical presentations. CONCLUSION. We have found it useful to separate these entities into groups on the basis of the distribution pattern (focal vs diffuse) and location (trachea vs bronchi). C1 [Ngo, Anh-Vu H.; Walker, Christopher Michael; Stern, Eric J.; Reddy, Gautham P.; Godwin, J. David] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Chung, Jonathan H.] Natl Jewish Hlth, Dept Radiol, Denver, CO USA. [Takasugi, Julie E.] Puget Sound VA Hlth Care Syst, Dept Radiol, Seattle, WA USA. [Kanne, Jeffrey P.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Walker, CM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM walk0060@gmail.com NR 50 TC 5 Z9 5 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2013 VL 201 IS 2 BP 301 EP 313 DI 10.2214/AJR.12.9043 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 188VT UT WOS:000322225400043 PM 23883210 ER PT J AU Czuczman, GJ Pomerantz, SR Alkasab, TK Huang, AJ AF Czuczman, Gregory J. Pomerantz, Stuart R. Alkasab, Tarik K. Huang, Ambrose J. TI Using a Web-Based Image Quality Assurance Reporting System to Improve Image Quality SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE image quality; quality assurance; quality control reporting; quality improvement; web-based tools ID HEALTH-CARE; RADIOLOGY AB OBJECTIVE. The purpose of this study is to show the impact of a web-based image quality assurance reporting system on the rates of three common image quality errors at our institution. MATERIALS AND METHODS. A web-based image quality assurance reporting system was developed and used beginning in April 2009. Image quality endpoints were assessed immediately before deployment (period 1), approximately 18 months after deployment of a prototype reporting system (period 2), and approximately 12 months after deployment of a subsequent upgraded department-wide reporting system (period 3). A total of 3067 axillary shoulder radiographs were reviewed for correct orientation, 355 shoulder CT scans were reviewed for correct reformatting of coronal and sagittal images, and 346 sacral MRI scans were reviewed for correct acquisition plane of axial images. Error rates for each review period were calculated and compared using the Fisher exact test. RESULTS. Error rates of axillary shoulder radiograph orientation were 35.9%, 7.2%, and 10.0%, respectively, for the three review periods. The decrease in error rate between periods 1 and 2 was statistically significant (p < 0.0001). Error rates of shoulder CT reformats were 9.8%, 2.7%, and 5.8%, respectively, for the three review periods. The decrease in error rate between periods 1 and 2 was statistically significant (p = 0.03). Error rates for sacral MRI axial sequences were 96.5%, 32.5%, and 3.4%, respectively, for the three review periods. The decrease in error rates between periods 1 and 2 and between periods 2 and 3 was statistically significant (p < 0.0001). CONCLUSION. A web-based system for reporting image quality errors may be effective for improving image quality. C1 [Czuczman, Gregory J.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. [Alkasab, Tarik K.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Imaging, Boston, MA 02114 USA. [Huang, Ambrose J.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP Huang, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM ajhuang@partners.org OI Alkasab, Tarik/0000-0002-4433-9482 NR 16 TC 1 Z9 1 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 AUG PY 2013 VL 201 IS 2 BP 361 EP 368 DI 10.2214/AJR.12.10292 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 188VT UT WOS:000322225400050 PM 23883217 ER PT J AU Nguyen, ML Gervais, DA Blake, MA Mueller, PR Sahani, DV Hahn, PF Uppot, RN AF Nguyen, My-Linh Gervais, Debra A. Blake, Michael A. Mueller, Peter R. Sahani, Dushyant V. Hahn, Peter F. Uppot, Raul N. TI Imaging-Guided Biopsy of F-18-FDG-Avid Extrapulmonary Lesions: Do Lesion Location and Morphologic Features on CT Affect the Positive Predictive Value for Malignancy? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE F-18-fluorodeoxyglucose; imaging-guided biopsy; interventional radiology; nuclear medicine; PET/CT ID POSITRON-EMISSION-TOMOGRAPHY; INTEGRATED FDG PET/CT; COLORECTAL-CANCER; ESOPHAGEAL CANCER; LIVER METASTASES; NECK MALIGNANCY; CELL-CARCINOMA; HEAD; RECURRENT; METAANALYSIS AB OBJECTIVE. The purpose of our study was to analyze the effect of lesion location and morphologic appearance on CT on the positive predictive value (PPV) for malignancy of all extrapulmonary lesions that were F-18-FDG avid on PET/CT and that were biopsied under imaging guidance. MATERIALS AND METHODS. Between January 2004 and December 2010, 227 patients underwent imaging-guided biopsy of 231 PET-positive extrapulmonary lesions with diagnostic pathologic results. The PET PPV for malignancy was retrospectively calculated and stratified according to lesion location and morphologic appearance. RESULTS. The overall PET PPV for malignancy was 72%. Inflammatory processes accounted for the majority of benign biopsy results. Lesion location significantly affected the PPV (p < 0.001). Bone (96%) and liver (90%) lesions had significantly higher PPVs for malignancy compared with other locations, whereas lymph nodes (60%) had a significantly lower PPV for malignancy. Lesions that were morphologically suspicious and morphologically benign according to CT findings alone were associated with PPVs of 74% and 57%, respectively (p = 0.05). FDG-avid subcentimeter lymph nodes (n = 8) had a PPV for malignancy of 38%. CONCLUSION. Over half of PET-avid morphologically benign-appearing lesions and one third of PET-avid subcentimeter lymph nodes were found to be malignant at biopsy, suggesting that benign morphologic appearance alone should not preclude further workup of a PET-positive lesion. Biopsies of FDG-avid lesions in liver and bone yielded high rates of true malignancy, whereas biopsies of lymph nodes yielded a lower rate of malignancy compared with other lesion locations. C1 [Nguyen, My-Linh] Harvard Univ, Sch Med, Peabody Soc, Boston, MA 02115 USA. [Nguyen, My-Linh; Gervais, Debra A.; Blake, Michael A.; Mueller, Peter R.; Sahani, Dushyant V.; Hahn, Peter F.; Uppot, Raul N.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Nguyen, ML (reprint author), Harvard Univ, Sch Med, Peabody Soc, 260 Longwood Ave, Boston, MA 02115 USA. EM mylinhnguyen@post.harvard.edu NR 31 TC 6 Z9 6 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2013 VL 201 IS 2 BP 433 EP 438 DI 10.2214/AJR.12.9166 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 188VT UT WOS:000322225400059 PM 23883226 ER PT J AU Jhaveri, K Gupta, P Elmi, A Flor, L Moshonov, H Evans, A Jewett, M AF Jhaveri, Kartik Gupta, Priya Elmi, Azadeh Flor, Lior Moshonov, Hadas Evans, Andrew Jewett, Michael TI Cystic Renal Cell Carcinomas: Do They Grow, Metastasize, or Recur? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; cystic renal cell carcinoma; growth patterns; imaging; MRI ID TERM-FOLLOW-UP; CANCER STATISTICS; CLASSIFICATION; RESECTION; MASSES; TUMORS; CT AB OBJECTIVE. The purpose of this study is to evaluate the interval growth, tumor recurrence, and metastatic disease occurrence of cystic renal cell carcinoma (RCC). MATERIALS AND METHODS. Pre- and posttreatment imaging of 47 histologically proven cystic RCCs, with at least 6 months of pretreatment imaging monitoring or at least 2 years of posttreatment imaging follow-up, or both, was retrospectively reviewed. Tumor morphologic features, preoperative growth, histologic typing and grading, and the incidence of tumor recurrence or metastasis were evaluated. Growth rate of tumors were compared among various histologic subtypes and Fuhrman grades. RESULTS. Of 47 tumors, 27 (57.5%) were clear cell RCCs, 12 (25.5%) were multilocular RCCs, and eight (17%) were papillary cystic RCCs. Overall, 26 (55.3%) tumors were graded as Fuhrman grade 2, 17 (36.1%) were Fuhrman grade 1, and one tumor was Fuhrman grade 3. Of the 26 tumors with a minimum of 6 months of pretreatment imaging monitoring, 19 (73%) did not show a significant increase in tumor size. The differences in mean growth among the Fuhrman grades and different subtypes were not statistically significant. The average duration of posttreatment follow-up was 51 months. There were no local recurrences among the 43 patients who underwent posttreatment imaging, except for one patient who had metastasis at preoperative clinical presentation. CONCLUSION. Cystic RCCs exhibit slow indolent growth, if any, and show no significant metastatic or recurrence potential, with excellent clinical outcomes. We raise the need for revisiting current imaging protocols that may involve frequent pre- and posttreatment imaging in cystic RCCs. C1 [Jhaveri, Kartik; Gupta, Priya; Flor, Lior; Moshonov, Hadas] Univ Toronto, Mt Sinai Hosp, Univ Hlth Network, Joint Dept Med Imaging, Toronto, ON M5G 2M9, Canada. [Jhaveri, Kartik; Gupta, Priya; Flor, Lior; Moshonov, Hadas] Univ Toronto, Womens Coll Hosp, Toronto, ON M5G 2M9, Canada. [Elmi, Azadeh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, Boston, MA USA. [Evans, Andrew] Univ Toronto, Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2M9, Canada. [Jewett, Michael] Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, Dept Surg Oncol,Div Urol, Toronto, ON M5G 2M9, Canada. RP Jhaveri, K (reprint author), Univ Toronto, Mt Sinai Hosp, Univ Hlth Network, Joint Dept Med Imaging, 3-957,610 Univ Ave, Toronto, ON M5G 2M9, Canada. NR 22 TC 17 Z9 20 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2013 VL 201 IS 2 BP W292 EP W296 DI 10.2214/AJR.12.9414 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 188VT UT WOS:000322225400014 PM 23883243 ER PT J AU Kalra, MK Woisetschlager, M Dahlstrom, N Singh, S Digumarthy, S Do, S Pien, H Quick, P Schmidt, B Sedlmair, M Shepard, JAO Persson, A AF Kalra, Mannudeep K. Woisetschlaeger, Mischa Dahlstroem, Nils Singh, Sarabjeet Digumarthy, Subbarao Do, Synho Pien, Homer Quick, Petter Schmidt, Bernhard Sedlmair, Martin Shepard, Jo-Anne O. Persson, Anders TI Sinogram-Affirmed Iterative Reconstruction of Low-Dose Chest CT: Effect on Image Quality and Radiation Dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE iterative reconstruction; low-dose chest CT; radiation dose reduction ID FILTERED BACK-PROJECTION; TUBE CURRENT MODULATION; REDUCTION; MDCT; ABDOMEN AB OBJECTIVE. The purpose of this study is to compare sinogram-affirmed iterative reconstruction (SAFIRE) and filtered back projection (FBP) reconstruction of chest CT acquired with 65% radiation dose reduction. SUBJECTS AND METHODS. In this prospective study involving 24 patients (11 women and 13 men; mean [+/- SD] age, 66 +/- 10 years), two scan series were acquired using 100 and 40 Quality Reference mAs over a 10-cm scan length in the chest with a 128-MDCT scanner. The 40 Quality Reference mAs CT projection data were reconstructed with FBP and four settings of Safire (S1, S2, S3, and S4). Six image datasets (FBP with 100 and 40 Quality Reference mAs, and S1, S2, S3, S4 with 40 Quality Reference mAs) were displayed on a DICOM-compliant 55-inch 2-megapixel monitor for blinded evaluation by two thoracic radiologists for number and location of lesions, lesion size, lesion margins, visibility of small structures and fissures, and diagnostic confidence. Objective noise and CT values were measured in thoracic aorta for each image series, and the noise power spectrum was assessed. Data were analyzed with analysis of variance and Wilcoxon signed rank tests. RESULTS. All 186 lesions were seen on 40 Quality Reference mAs SAFIRE images. Diagnostic confidence on SAFIRE images was higher than that for FBP images. Except for the minor blotchy appearance on SAFIRE settings S3 and S4, no significant artifacts were noted. Objective noise with 40 Quality Reference mAs S1 images (21.1 +/- 6.1 SD of HU) was significantly lower than that for 40 Quality Reference mAs FBP images (28.5 +/- 8.1 SD of HU) (p < 0.001). Noise power spectra were identical for SAFIRE and FBP with progressive noise reduction with higher iteration SAFIRE settings. CONCLUSION. Iterative reconstruction (SAFIRE) allows reducing the radiation exposure by approximately 65% without losing diagnostic information in chest CT. C1 [Kalra, Mannudeep K.; Singh, Sarabjeet; Digumarthy, Subbarao; Do, Synho; Pien, Homer; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Imaging, Boston, MA 02114 USA. [Woisetschlaeger, Mischa; Dahlstroem, Nils; Quick, Petter; Persson, Anders] Linkoping Univ, Ctr Med Image Sci & Visualizat, SE-58185 Linkoping US, Sweden. [Schmidt, Bernhard; Sedlmair, Martin] Siemens Healthcare, Forchheim, Germany. RP Persson, A (reprint author), Linkoping Univ, Ctr Med Image Sci & Visualizat, SE-58185 Linkoping US, Sweden. EM anders.persson@cmiv.liu.se RI Persson, Anders/L-1004-2013 OI Persson, Anders/0000-0002-9446-6981 FU Siemens Healthcare FX B. Schmidt and M. Sedlmair are employees of Siemens Healthcare. S. Do and H. Pien have received research grants from Siemens Healthcare. The remaining coauthors do not have any pertinent financial disclosure and had complete and unrestricted access to the data and manuscript throughout the course of the study. NR 19 TC 30 Z9 30 U1 1 U2 8 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 AUG PY 2013 VL 201 IS 2 BP W235 EP W244 DI 10.2214/AJR.12.9569 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 188VT UT WOS:000322225400008 PM 23883238 ER PT J AU Shinagare, AB Ramaiya, NH AF Shinagare, Atul B. Ramaiya, Nikhil H. TI Portal Venous Gas Secondary to Molecular Targeted Therapy Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 [Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 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 AUG PY 2013 VL 201 IS 2 BP W370 EP W370 DI 10.2214/AJR.13.10818 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 188VT UT WOS:000322225400035 PM 23883264 ER PT J AU Teng, E Leone-Friedman, J Lee, GJ Woo, S Apostolova, LG Harrell, S Ringman, JM Lu, PH AF Teng, Edmond Leone-Friedman, Judith Lee, Grace J. Woo, Stephanie Apostolova, Liana G. Harrell, Shelly Ringman, John M. Lu, Po H. TI Similar Verbal Fluency Patterns in Amnestic Mild Cognitive Impairment and Alzheimer's Disease SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Mild cognitive impairment; Alzheimer's disease; Verbal fluency; Dementia; Assessment; Cognition ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; OLDER-ADULTS; DEMENTIA; SUBTYPES; CONVERSION; AGE; EDUCATION; MCI; VARIABILITY; DISCREPANCY AB Disproportionately greater deficits in semantic relative to phonemic verbal fluency are seen in Alzheimer's disease (AD) and have been attributed to neurodegenerative changes in the temporal lobe. Amnestic (AMN) mild cognitive impairment (MCI), which often represents incipient AD, is also characterized by early temporal lobe neuropathology, but previous comparisons of verbal fluency between AD and AMN MCI have yielded mixed results. We examined semantic and phonemic verbal fluency performance in 399 individuals (78 AD, 138 AMN MCI, 72 non-amnestic MCI, and 111 cognitively normal controls). Similar verbal fluency patterns were seen in AMN MCI and AD; both groups exhibited disproportionately poorer performance on semantic verbal fluency relative to normal controls. However, relative verbal fluency indices performed more poorly than individual semantic or phonemic verbal fluency indices for discriminating AMN MCI or AD participants from normal controls, suggesting that they are unlikely to provide additional utility for predicting progression from MCI to AD. C1 [Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA. [Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Teng, Edmond; Leone-Friedman, Judith; Apostolova, Liana G.; Ringman, John M.] Univ Calif Los Angeles, David Geffen Sch Med, Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA. [Teng, Edmond; Leone-Friedman, Judith; Apostolova, Liana G.; Ringman, John M.; Lu, Po H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Lee, Grace J.] Loma Linda Univ, Dept Psychol, Loma Linda, CA 92350 USA. [Woo, Stephanie; Harrell, Shelly] Pepperdine Univ, Grad Sch Educ & Psychol, Los Angeles, CA USA. RP Lu, PH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, RNRC, 710 Westwood Plaza,Room 2-258, Los Angeles, CA 90095 USA. EM plu@mednet.ucla.edu FU NIH from the National Institute on Aging [P50 AG 16570, K23 AG 028727, K08 AG 34628]; National Institute on Aging; American Federation for Aging Research; John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation; Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation; Jim Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarkers at UCLA FX This research was supported by NIH grants from the National Institute on Aging (P50 AG 16570, K23 AG 028727 to PL and K08 AG 34628 to ET; jointly sponsored by the National Institute on Aging, American Federation for Aging Research, the John A. Hartford Foundation, the Atlantic Philanthropies, the Starr Foundation and an anonymous donor), the Alzheimer's Disease Research Centers of California, the Sidell-Kagan Foundation, and the Jim Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarkers at UCLA. NR 43 TC 5 Z9 5 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD AUG PY 2013 VL 28 IS 5 BP 400 EP 410 DI 10.1093/arclin/act039 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA 186CN UT WOS:000322019600002 PM 23752677 ER PT J AU Gradl, G Jupiter, J Pillukat, T Knobe, M Prommersberger, KJ AF Gradl, Gertraud Jupiter, Jesse Pillukat, Thomas Knobe, Matthias Prommersberger, Karl-Josef TI Corrective osteotomy of the distal radius following failed internal fixation SO ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY LA English DT Article DE Corrective osteotomy; Distal radius malunion; Initial operative treatment; Failed internal fixation ID LOW-PROFILE DORSAL; MALUNITED FRACTURES; ILIAC CREST; LOCKING PLATES; VOLAR; COMPLICATIONS; STRENGTH; OUTCOMES; CEMENT; GRIP AB The purpose of this study was to quantify the clinical and radiographic outcomes after corrective osteotomy for malunions of the distal radius following failed internal fixation. Results of 18 patients (8 women, 10 men; mean age 41 years) are presented an average of 7 years after osteotomy of a malunited distal radius fracture. We assessed active range of motion, grip strength, radiographic alignment, pain and disability. Subjective and objective data were summarized using the modified Mayo Wrist Score and the point-score system of Fernandez. Wrist motion, pain and deformity improved with the operation in all cases. The modified Mayo Wrist Score averaged 79 points. The scale of Fernandez indicated ten good, two fair and six poor results. The results of this study suggest that the operative correction of a distal radius malunion following an unsuccessful internal fixation can be achieved with outcomes comparable to those reported after initial nonoperative treatment. C1 [Gradl, Gertraud; Knobe, Matthias] Univ Aachen, Dept Trauma & Reconstruct Surg, D-52074 Aachen, Germany. [Gradl, Gertraud; Jupiter, Jesse] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Pillukat, Thomas; Prommersberger, Karl-Josef] Rhon Klinikum AG, Klin Handchirurg, D-97617 Bad Neustadt an der Saale, Germany. RP Gradl, G (reprint author), Univ Aachen, Dept Trauma & Reconstruct Surg, Pauwelstr 30, D-52074 Aachen, Germany. EM ggradl@ukaachen.de NR 31 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0936-8051 J9 ARCH ORTHOP TRAUM SU JI Arch. Orthop. Trauma Surg. PD AUG PY 2013 VL 133 IS 8 BP 1173 EP 1179 DI 10.1007/s00402-013-1779-5 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 187PS UT WOS:000322131700020 PM 23708289 ER PT J AU Bae, ON Wang, JM Baek, SH Wang, Q Yuan, H Chen, AF AF Bae, Ok-Nam Wang, Jie-Mei Baek, Seung-Hoon Wang, Qingde Yuan, Hong Chen, Alex F. TI Oxidative Stress-Mediated Thrombospondin-2 Upregulation Impairs Bone Marrow-Derived Angiogenic Cell Function in Diabetes Mellitus SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE angiogenesis inhibitors; diabetes; oxidative stress; stem cells; thrombospondin-2; human ID ENDOTHELIAL PROGENITOR CELLS; MANGANESE SUPEROXIDE-DISMUTASE; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE SYNTHASE; MICRORNA EXPRESSION; TUMOR ANGIOGENESIS; PROLIFERATION; PATHOPHYSIOLOGY; MECHANISMS; PHENOTYPE AB Objective Circulating angiogenic cells play an essential role in angiogenesis but are dysfunctional in diabetes mellitus characterized by excessive oxidative stress. We hypothesize that oxidative stress-mediated upregulation of thrombospondin-2 (TSP-2), a potent antiangiogenic protein, contributes to diabetic bone marrow-derived angiogenic cell (BMAC) dysfunction. Approach and Results BMACs were isolated from adult male type 2 diabetic db/db mice and control db/+ (C57BLKS/J) mice. In Matrigel tube formation assay, angiogenic function was impaired in diabetic BMACs, accompanied by increased oxidative stress and nicotinamide adenine dinucleotide phosphate oxidase activity. BMAC angiogenic function was restored by overexpression of dominant negative Rac1 or by overexpression of manganese superoxide dismutase. TSP-2 mRNA and protein were both significantly upregulated in diabetic BMACs, mediated by increased oxidative stress as shown by a decrease in TSP-2 level after overexpression of dominant negative Rac1 or manganese superoxide dismutase. Silencing TSP-2 by its small interfering RNA in diabetic BMACs improved BMAC function in tube formation, adhesion, and migration assays. Notably, the upregulation of TSP-2 was also found in BMACs from streptozotocin-induced type 1 diabetic mice, and normal BMACs with high glucose treatment. let-7f, a microRNA which has been related to endothelial angiogenic function, is found to play key role in TSP-2 increase, but let-7f did not directly interact with TSP-2 mRNA. Conclusions The upregulation of TSP-2 mediated by increased oxidative stress contributes to angiogenesis dysfunction in diabetic BMACs. C1 [Wang, Jie-Mei; Wang, Qingde; Yuan, Hong; Chen, Alex F.] Cent S Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Dept Cardiol, Changsha 410013, Hunan, Peoples R China. [Wang, Jie-Mei; Wang, Qingde; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Wang, Jie-Mei; Wang, Qingde; Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bae, Ok-Nam; Baek, Seung-Hoon] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA. [Bae, Ok-Nam] Hanyang Univ, Coll Pharm, Ansan, South Korea. [Baek, Seung-Hoon] Ajou Univ, Coll Pharm, Suwon 441749, Gyeonggido, South Korea. RP Chen, AF (reprint author), Cent S Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Dept Cardiol, 138 Tong Zi Bo Rd, Changsha 410013, Hunan, Peoples R China. EM afychen@yahoo.com OI WANG, JIEMEI/0000-0002-8723-4410 FU National Institutes of Health (NIH)/National Institute of General Medical Sciences [R01 GM077352]; United States Department of Veterans Affairs Rehabilitation Research & Development Merit Awards [I01RX000244, 1I01RX000652]; American Diabetes Association [7-11-BS-23]; National Science Foundation of China Key Research Project [81130004]; NIH [1R21CA158650]; Korea Research Foundation [2012R1A1A3013240]; American Heart Association [0920110G]; China Oversea Scholarship [20070320] FX This work was supported in part by National Institutes of Health (NIH)/National Institute of General Medical Sciences R01 GM077352 (to A.F. Chen), United States Department of Veterans Affairs Rehabilitation Research & Development Merit Awards I01RX000244 and 1I01RX000652 (to Dr Chen), American Diabetes Association Research Award 7-11-BS-23 (to Dr Chen), the National Science Foundation of China Key Research Project 81130004 (to Dr Chen) and NIH 1R21CA158650 (to Q. Wang). Dr Bae is the receipt of a research fund from the Korea Research Foundation (2012R1A1A3013240). J.-M. Wang the receipt of the American Heart Association Postdoctoral Fellowship 0920110G and the China Oversea Scholarship 20070320. NR 40 TC 13 Z9 14 U1 0 U2 8 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 AUG PY 2013 VL 33 IS 8 BP 1920 EP 1927 DI 10.1161/ATVBAHA.113.301609 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 188IW UT WOS:000322187600028 PM 23723366 ER PT J AU Cefalu, AB Pirruccello, JP Noto, D Gabriel, S Valenti, V Gupta, N Spina, R Tarugi, P Kathiresan, S Averna, MR AF Cefalu, Angelo B. Pirruccello, James P. Noto, Davide Gabriel, Stacey Valenti, Vincenza Gupta, Namrata Spina, Rossella Tarugi, Patrizia Kathiresan, Sekar Averna, Maurizio R. TI A Novel APOB Mutation Identified by Exome Sequencing Cosegregates With Steatosis, Liver Cancer, and Hypocholesterolemia SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE carcinoma; hepatocellular; exome; fatty liver; hypobetalipoproteinemia; familial; 1 ID FAMILIAL HYPOBETALIPOPROTEINEMIA; FATTY LIVER; APOLIPOPROTEIN-B; HETEROZYGOUS HYPOBETALIPOPROTEINEMIA; TRUNCATED FORM; IN-VIVO; SECRETION; GENE; CHOLESTEROL; POPULATION AB Objective In familial hypobetalipoproteinemia, fatty liver is a characteristic feature, and there are several reports of associated cirrhosis and hepatocarcinoma. We investigated a large kindred in which low-density lipoprotein cholesterol, fatty liver, and hepatocarcinoma displayed an autosomal dominant pattern of inheritance. Approach and Results The proband was a 25-year-old female with low plasma cholesterol and hepatic steatosis. Low plasma levels of total cholesterol and fatty liver were observed in 10 more family members; 1 member was affected by liver cirrhosis, and 4 more subjects died of either hepatocarcinoma or carcinoma on cirrhosis. To identify the causal mutation in this family, we performed exome sequencing in 2 participants with hypocholesterolemia and fatty liver. Approximately 22400 single nucleotide variants were identified in each sample. After variant filtering, 300 novel shared variants remained. A nonsense variant, p.K2240X, attributable to an A>T mutation in exon 26 of APOB (c.6718A>T) was identified, and this variant was confirmed by Sanger sequencing. The gentotypic analysis of 16 family members in total showed that this mutation segregated with the low cholesterol trait. In addition, genotyping of the PNPLA3 p.I148M did not show significant frequency differences between carriers and noncarriers of the c.6718A>T APOB gene mutation. Conclusions We used exome sequencing to discover a novel nonsense mutation in exon 26 of APOB (p.K2240X) responsible for low cholesterol and fatty liver in a large kindred. This mutation may also be responsible for cirrhosis and liver cancer in this family. C1 [Cefalu, Angelo B.; Noto, Davide; Valenti, Vincenza; Spina, Rossella; Averna, Maurizio R.] Univ Palermo, Dipartimento Biomed Med Interna & Specialist, I-90127 Palermo, Italy. [Pirruccello, James P.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pirruccello, James P.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Pirruccello, James P.; Gabriel, Stacey; Gupta, Namrata; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Tarugi, Patrizia] Univ Modena, Dept Life Sci, I-41100 Modena, Italy. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA. RP Averna, MR (reprint author), Univ Palermo, Dipartimento Biomed Med Interna & Specialist DIBI, Policlin Paolo Giaccone, Via Vespro 141, I-90127 Palermo, Italy. EM maurizio.averna@unipa.it RI Tarugi, Patrizia/D-2179-2015; OI Tarugi, Patrizia/0000-0001-6864-7853; Noto, Davide/0000-0002-5346-2829; Cefalu', Angelo Baldassare/0000-0003-1259-8284; Averna, Maurizio/0000-0003-3558-9209 FU University of Palermo; Italian Ministry of Education, University and Research [2009-RLKXPF]; Fondazione Cassa di Risparmio di Modena; Sarnoff Cardiovascular Research Foundation; Massachusetts General Hospital; Donovan Family Foundation; US National Institutes of Health [R01 HL-107816] FX This work was supported by contract grants from the University of Palermo (60% to M. R. Averna and A. B. Cefalu), Grant 2009-RLKXPF PRIN 2009 from the Italian Ministry of Education, University and Research (to M. R. Averna), the Fondazione Cassa di Risparmio di Modena (to P. Tarugi); J.P. Pirruccello was supported by the Sarnoff Cardiovascular Research Foundation. S. Kathiresan is supported by a Howard Goodman Fellowship and a Research Scholar Award from the Massachusetts General Hospital, the Donovan Family Foundation, and R01 HL-107816 from the US National Institutes of Health. NR 30 TC 25 Z9 26 U1 1 U2 5 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 AUG PY 2013 VL 33 IS 8 BP 2021 EP 2025 DI 10.1161/ATVBAHA.112.301101 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 188IW UT WOS:000322187600041 PM 23723369 ER PT J AU Borissoff, JI Joosen, IA Versteylen, MO Brill, A Fuchs, TA Savchenko, AS Gallant, M Martinod, K ten Cate, H Hofstra, L Crijns, HJ Wagner, DD Kietselaer, BLJH AF Borissoff, Julian I. Joosen, Ivo A. Versteylen, Mathijs O. Brill, Alexander Fuchs, Tobias A. Savchenko, Alexander S. Gallant, Maureen Martinod, Kimberly ten Cate, Hugo Hofstra, Leonard Crijns, Harry J. Wagner, Denisa D. Kietselaer, Bas L. J. H. TI Elevated Levels of Circulating DNA and Chromatin Are Independently Associated With Severe Coronary Atherosclerosis and a Prothrombotic State SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; coagulation; blood; chromatin; DNA; neutrophils; nucleosomes; thrombin; thrombophilia ID NEUTROPHIL EXTRACELLULAR TRAPS; DEEP-VEIN THROMBOSIS; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; DEOXYRIBONUCLEASE-I ACTIVITY; ACUTE MYOCARDIAL-INFARCTION; ARTERY-DISEASE; INNATE IMMUNITY; HISTONES; MICE; MECHANISMS AB Objective Aberrant neutrophil activation occurs during the advanced stages of atherosclerosis. Once primed, neutrophils can undergo apoptosis or release neutrophil extracellular traps. This extracellular DNA exerts potent proinflammatory, prothrombotic, and cytotoxic properties. The goal of this study was to examine the relationships among extracellular DNA formation, coronary atherosclerosis, and the presence of a prothrombotic state. Approach and Results In a prospective, observational, cross-sectional cohort of 282 individuals with suspected coronary artery disease, we examined the severity, extent, and phenotype of coronary atherosclerosis using coronary computed tomographic angiography. Double-stranded DNA, nucleosomes, citrullinated histone H4, and myeloperoxidase-DNA complexes, considered in vivo markers of cell death and NETosis, respectively, were established. We further measured various plasma markers of coagulation activation and inflammation. Plasma double-stranded DNA, nucleosomes, and myeloperoxidase-DNA complexes were positively associated with thrombin generation and significantly elevated in patients with severe coronary atherosclerosis or extremely calcified coronary arteries. Multinomial regression analysis, adjusted for confounding factors, identified high plasma nucleosome levels as an independent risk factor of severe coronary stenosis (odds ratio, 2.14; 95% confidence interval, 1.26-3.63; P=0.005). Markers of neutrophil extracellular traps, such as myeloperoxidase-DNA complexes, predicted the number of atherosclerotic coronary vessels and the occurrence of major adverse cardiac events. Conclusions Our report provides evidence demonstrating that markers of cell death and neutrophil extracellular trap formation are independently associated with coronary artery disease, prothrombotic state, and occurrence of adverse cardiac events. These biomarkers could potentially aid in the prediction of cardiovascular risk in patients with chest discomfort. C1 [Borissoff, Julian I.; Brill, Alexander; Fuchs, Tobias A.; Savchenko, Alexander S.; Gallant, Maureen; Martinod, Kimberly; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Borissoff, Julian I.; Brill, Alexander; Fuchs, Tobias A.; Savchenko, Alexander S.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Martinod, Kimberly] Harvard Univ, Sch Med, Div Med Sci, Grad Program Immunol, Boston, MA 02115 USA. [Borissoff, Julian I.; ten Cate, Hugo] Maastricht Univ, Med Ctr, Cardiovasc Res Inst, Dept Internal Med,Lab Clin Thrombosis & Hemostasi, Maastricht, Netherlands. [Joosen, Ivo A.; Versteylen, Mathijs O.; Crijns, Harry J.; Kietselaer, Bas L. J. H.] Maastricht Univ, Med Ctr, Cardiovasc Res Inst, Dept Cardiol, Maastricht, Netherlands. [Kietselaer, Bas L. J. H.] Maastricht Univ, Med Ctr, Cardiovasc Res Inst, Dept Radiol, Maastricht, Netherlands. [Hofstra, Leonard] Cardiol Ctr Netherlands, Utrecht, Netherlands. RP Borissoff, JI (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM Julian.Borissoff@childrens.harvard.edu OI ten Cate, Hugo/0000-0001-7796-4463; Martinod, Kimberly/0000-0002-1026-6107 FU Netherlands Heart Foundation; Maastricht University; Netherlands Organization for Scientific Research [825.11.019]; National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL102101] FX This work was supported by the Netherlands Heart Foundation. Dr Borissoff is a recipient of a Kootstra Talent Fellowship (2011) from Maastricht University and is supported by a Rubicon fellowship (825.11.019), granted by the Netherlands Organization for Scientific Research. Dr Wagner is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (Grant R01 HL102101). Dr ten Cate is a fellow of the Gutenberg Research College (Gutenberg University, Mainz, Germany). NR 50 TC 77 Z9 78 U1 0 U2 12 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 AUG PY 2013 VL 33 IS 8 BP 2032 EP 2040 DI 10.1161/ATVBAHA.113.301627 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 188IW UT WOS:000322187600043 PM 23818485 ER PT J AU Ahn, J Yuan, Y Parmigiani, G Suraokar, MB Diao, LX Wistuba, II Wang, WY AF Ahn, Jaeil Yuan, Ying Parmigiani, Giovanni Suraokar, Milind B. Diao, Lixia Wistuba, Ignacio I. Wang, Wenyi TI DeMix: deconvolution for mixed cancer transcriptomes using raw measured data SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; MICROARRAY DATA; COMPLEX TISSUES; PATTERNS; NORMALIZATION; EXPLORATION AB Motivation: Tissue samples of tumor cells mixed with stromal cells cause underdetection of gene expression signatures associated with cancer prognosis or response to treatment. In silico dissection of mixed cell samples is essential for analyzing expression data generated in cancer studies. Currently, a systematic approach is lacking to address three challenges in computational deconvolution: (i) violation of linear addition of expression levels from multiple tissues when logtransformed microarray data are used; (ii) estimation of both tumor proportion and tumor-specific expression, when neither is known a priori; and (iii) estimation of expression profiles for individual patients. Results: We have developed a statistical method for deconvolving mixed cancer transcriptomes, DeMix, which addresses the aforementioned issues in array-based expression data. We demonstrate the performance of our model in synthetic and real, publicly available, datasets. DeMix can be applied to ongoing biomarker-based clinical studies and to the vast expression datasets previously generated from mixed tumor and stromal cell samples. C1 [Ahn, Jaeil; Wang, Wenyi] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Ahn, Jaeil; Yuan, Ying; Diao, Lixia] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Suraokar, Milind B.; Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol Thorac Head & Neck Med O, Houston, TX 77030 USA. RP Wang, WY (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. EM wwang7@mdanderson.org FU IASLC Young Investigator Award; [1R01 CA174206-01]; [R01 CA154591]; [5P30 CA006516-46]; [NSF 3501501]; [W81XWH-07-1-0306]; [5U24 CA143883-04]; [P30 CA016672] FX J.A. is in part funded by 1R01 CA174206-01. Y.Y. is in part funded by R01 CA154591. G. P. is funded by 1R01 CA174206-01, 5P30 CA006516-46, NSF 3501501. M. S. is funded by IASLC Young Investigator Award. I. I. W. is funded by W81XWH-07-1-0306. W. W. is in part funded by 1R01 CA174206-01, 5U24 CA143883-04, P30 CA016672. NR 22 TC 17 Z9 17 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 1 PY 2013 VL 29 IS 15 BP 1865 EP 1871 DI 10.1093/bioinformatics/btt301 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 190JY UT WOS:000322337000004 PM 23712657 ER PT J AU Olson, EM Najita, JS Sohl, J Arnaout, A Burstein, HJ Winer, EP Lin, NU AF Olson, Erin M. Najita, Julie S. Sohl, Jessica Arnaout, Amal Burstein, Harold J. Winer, Eric P. Lin, Nancy U. TI Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era SO BREAST LA English DT Article DE Breast cancer; Central nervous system; HER2; Metastases; Trastuzumab ID LAPATINIB PLUS CAPECITABINE; RANDOMIZED PHASE-II; BRAIN METASTASES; MONOCLONAL-ANTIBODY; 1ST-LINE TREATMENT; WOMEN; THERAPY; EFFICACY; SAFETY; CHEMOTHERAPY AB Background: Trastuzumab is associated with improvements in overall survival (OS) among patients with HER2-positive metastatic breast cancer (MBC); however disease course and patterns of care in individual patients are highly variable. Methods: 113 HER2-positive patients diagnosed with MBC from 1999 to 2005 who received trastuzumab-based therapy were retrospectively identified to allow for a minimum of 5 years of follow-up time. Median OS and median duration of therapy were determined using Kaplan Meier methodology and group comparisons were based on the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model. Results: Median OS was 3.5 years (95% CI 3.0-4.4) from time of initiation of first therapy in the metastatic setting. On univariate analysis, central nervous system (CNS) disease at first recurrence was associated with a shorter OS compared with liver and/or lung metastases or other sites (CNS: 1.9 years CI 0.1-5.9, liver/lung: 3.2 years CI 2.5-4.2, other: 4.6 years Cl 2.7-8.0; p = 0.05), however, this was not predictive of survival outcome in multivariate analysis. CNS metastases developed in 62 (55%) patients by the time of death or last follow-up. Median duration of therapy was similar up to 6 lines of treatment, and ranged from 5.2 months to 7.2 months. Conclusions: The natural history of HER2-positive MBC has evolved with trastuzumab-based therapy with median OS now exceeding 3 years. CNS disease is a major problem with continued risk of CNS progression over time. Patients demonstrate clinical benefit to multiple lines of HER2-directed therapy. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Olson, Erin M.] Ohio State Univ, Coll Med, Arthur G James Canc Hosp, Columbus, OH 43210 USA. [Olson, Erin M.] Ohio State Univ, Coll Med, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Najita, Julie S.; Sohl, Jessica; Arnaout, Amal; Burstein, Harold J.; Winer, Eric P.; Lin, Nancy U.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Olson, EM (reprint author), B407 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43212 USA. EM Erin.olson@osumc.edu FU Genentech Inc.; National Cancer Institute [K12 CA 133250] FX NUL and EPW receive research support from Genentech Inc.; EMO is supported by Translational Grant No. K12 CA 133250 in experimental therapeutics from the National Cancer Institute. NR 26 TC 33 Z9 33 U1 0 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD AUG PY 2013 VL 22 IS 4 BP 525 EP 531 DI 10.1016/j.breast.2012.12.006 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 183FF UT WOS:000321799000024 PM 23352568 ER PT J AU Lu, D Joshi, A Wang, B Olsen, S Yi, JH Krop, IE Burris, HA Girish, S AF Lu, Dan Joshi, Amita Wang, Bei Olsen, Steve Yi, Joo-Hee Krop, Ian E. Burris, Howard A. Girish, Sandhya TI An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer SO CLINICAL PHARMACOKINETICS LA English DT Article ID POPULATION PHARMACOKINETICS; PHASE-II; RECEPTOR; AMPLIFICATION; ONCOGENE AB Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer previously treated with trastuzumab and taxane chemotherapy. It comprises the microtubule inhibitory cytotoxic agent DM1 conjugated to the HER2-targeted humanized monoclonal antibody trastuzumab via a stable linker. To characterize the pharmacokinetics of T-DM1 in patients with metastatic breast cancer, concentrations of multiple analytes were quantified, including serum concentrations of T-DM1 conjugate and total trastuzumab (the sum of conjugated and unconjugated trastuzumab), as well as plasma concentrations of DM1. The clearance of T-DM1 conjugate is approximately 2 to 3 times faster than its parent antibody, trastuzumab. However, the clearance pathways accounting for this faster clearance rate are unclear. An integrated population pharmacokinetic model that simultaneously fits the pharmacokinetics of T-DM1 conjugate and total trastuzumab can help to elucidate the clearance pathways of T-DM1. The model can also be used to predict total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic data, thereby reducing the frequency of pharmacokinetic sampling. T-DM1 conjugate and total trastuzumab serum concentration data, including baseline trastuzumab concentrations prior to T-DM1 treatment, from phase I and II studies were used to develop this integrated population pharmacokinetic model. Based on a hypothetical T-DM1 catabolism scheme, two-compartment models for T-DM1 conjugate and trastuzumab were integrated by assuming a one-step deconjugation clearance from T-DM1 conjugate to trastuzumab. The ability of the model to predict the total trastuzumab pharmacokinetic profile based on T-DM1 conjugate pharmacokinetics and various sampling schemes of total trastuzumab pharmacokinetics was assessed to evaluate total trastuzumab sampling schemes. The final model reflects a simplified catabolism scheme of T-DM1, suggesting that T-DM1 clearance pathways include both deconjugation and proteolytic degradation. The model fits T-DM1 conjugate and total trastuzumab pharmacokinetic data simultaneously. The deconjugation clearance of T-DM1 was estimated to be similar to 0.4 L/day. Proteolytic degradation clearances for T-DM1 and trastuzumab were similar (similar to 0.3 L/day). This model accurately predicts total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic data sampled at preinfusion and end of infusion in cycle 1, and in one additional steady state cycle. This semi-mechanistic integrated model links T-DM1 conjugate and total trastuzumab pharmacokinetic data, and supports the inclusion of both proteolytic degradation and deconjugation as clearance pathways in the hypothetical T-DM1 catabolism scheme. The model attributes a faster T-DM1 conjugate clearance versus that of trastuzumab to the presence of a deconjugation process and suggests a similar proteolytic clearance of T-DM1 and trastuzumab. Based on the model and T-DM1 conjugate pharmacokinetic data, a sparse pharmacokinetic sampling scheme for total trastuzumab provides an entire pharmacokinetic profile with similar predictive accuracy to that of a dense pharmacokinetic sampling scheme. C1 [Lu, Dan; Joshi, Amita; Wang, Bei; Olsen, Steve; Yi, Joo-Hee; Girish, Sandhya] Genentech Inc, San Francisco, CA 94080 USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burris, Howard A.] Sarah Cannon Res Inst, Nashville, TN USA. RP Lu, D (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. EM lu.dan@gene.com FU Genentech, Inc. FX The authors acknowledge the investigators, patients and their families who participated in these clinical trials. The authors acknowledge Jin Yan Jin, PhD, for scientific input and helpful discussions during the preparation of this report. Support for third-party editorial assistance for this manuscript, furnished by Denise Chun, Ph.D. (CodonMedical), was provided by Genentech, Inc. The clinical studies reported here were sponsored by Genentech, Inc. Dan Lu, Amita Joshi, Bei Wang, Steve Olsen, Joo-Hee Yi and Sandhya Girish are employees of Genentech, Inc., and have Roche stock/stock options. Ian E. Krop receives clinical trial support from Genentech, Inc. Howard A. Burris has no conflicts of interest to declare. NR 40 TC 16 Z9 16 U1 3 U2 29 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD AUG PY 2013 VL 52 IS 8 BP 657 EP 672 DI 10.1007/s40262-013-0060-y PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 185ZP UT WOS:000322010900004 PM 23553425 ER PT J AU Joo, MJ Sharp, LK Au, DH Lee, TA Fitzgibbon, ML AF Joo, Min J. Sharp, Lisa K. Au, David H. Lee, Todd A. Fitzgibbon, Marian L. TI Use of Spirometry in the Diagnosis of COPD: A Qualitative Study in Primary Care SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE chronic disease; diagnosis; pulmonary diseases; qualitative research ID OBSTRUCTIVE PULMONARY-DISEASE; GENERAL-PRACTICE; OFFICE SPIROMETRY; CONTROLLED-TRIAL; MANAGEMENT; ASTHMA; ACCURACY; HISTORY; RISK AB Guidelines that recommend spirometry to confirm airflow obstruction among patients with suspected COPD are not routinely followed. We conducted a qualitative study to identify attitudes and barriers of primary care physicians to performing spirometry for patients with possible COPD. We conducted four focus groups, each with three primary care physicians (PCPs) who practice in an urban, academic medical center. In general, PCPs believed that spirometry was not necessary to confirm the diagnosis of COPD. Compared to other co-morbid conditions, in a patient with a diagnosis of COPD without self-reported symptoms, COPD was not a priority during a clinic visit. This was in part due to the belief that there was lack of evidence that medication used in COPD lead to improved outcomes and that there was no point of care measure for COPD compared to other co-morbid conditions such as diabetes mellitus or hypertension. Health system barriers specific to spirometry use was not identified. In conclusion, in our sample of PCPs, there was skepticism that spirometry is warranted to diagnose and manage COPD. Availability of spirometry was not a perceived barrier. Our results explain, in part, why previous interventions to improve access to spirometry and diagnosis of COPD in primary care settings have been difficult to conduct and/or have had marginal success. Our findings strongly suggest that a first step toward increasing the use of spirometry among primary care physicians is to have them believe in its utility in the diagnosis of COPD. C1 [Joo, Min J.] Univ Illinois Hosp & Hlth Sci Syst, Dept Med, Sect Pulm Crit Care Sleep & Allergy, Chicago, IL 60612 USA. [Joo, Min J.; Sharp, Lisa K.; Fitzgibbon, Marian L.] Univ Illinois Hosp & Hlth Sci Syst, Dept Med, Sect Hlth Promot Res, Chicago, IL 60612 USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Lee, Todd A.] Univ Illinois Hosp & Hlth Sci Syst, Dept Pharm Practice, Ctr Pharmacoecon Res, Chicago, IL 60612 USA. RP Joo, MJ (reprint author), Univ Illinois Hosp & Hlth Sci Syst, Dept Med, Sect Pulm Crit Care Sleep & Allergy, 840 S Wood St,M-C 719, Chicago, IL 60612 USA. EM joo@uic.edu FU Bosch Inc.; Gilead Sciences; NHLBI [K23HL094461]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health [UL1RR029879]; Department of Veterans Affairs FX Min Joo has no conflicts of interest to disclose. Lisa Sharp has no conflicts of interest to disclose. David Au has received funding as a research consultant for Bosch Inc. and research funding from Gilead Sciences in the past three years. Todd Lee has no conflicts of interest to disclose. Marian Fitzgibbon has no conflicts of interest to disclose.; The project described was supported by Award Number K23HL094461 from the NHLBI and also supported, in part, by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1RR029879. Dr. Au was supported by the Department of Veterans Affairs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, And Blood Institute, the National Institutes of Health or the Department of Veterans Affairs. NR 23 TC 8 Z9 8 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD AUG PY 2013 VL 10 IS 4 BP 444 EP 449 DI 10.3109/15412555.2013.766683 PG 6 WC Respiratory System SC Respiratory System GA 186TX UT WOS:000322069500007 PM 23537230 ER PT J AU Jakobiec, FA Gragoudas, ES Colby, KA AF Jakobiec, Frederick A. Gragoudas, Evangelos S. Colby, Kathryn A. TI Biopsy of an Anterior Episcleral Nodule as an Aid in Managing a Ciliary Body Melanocytic Tumor SO CORNEA LA English DT Article DE episcleral nodule; ciliary body tumor; nevus; melanoma; biopsy; HMB-45; MART-1; MiTF; Ki67 ID ULTRASOUND BIOMICROSCOPY; EXTRASCLERAL EXTENSION; MELANOMA; UVEAL AB Purpose: To demonstrate the value of a diagnostic biopsy of a fixed episcleral nodule overlying a uveal mass. Method: Clinicopathologic report with immunohistochemical investigations. Results: B-scan ultrasonographic biomicroscopy disclosed in a 67-year-old man an asymptomatic placoid ciliary body tumor measuring 1.28 mm in thickness underlying a poorly pigmented, fixed episcleral nodule 0.56 mm in thickness. Biopsy of the episcleral nodule displayed benign nevus-type spindle cells with small nuclei, punctate nucleoli, no mitoses, and scattered melanophages. Immunohistochemistry demonstrated that the tumor cells were Ki67 negative (proliferation index, 0) and MART-1, HMB-45, and microphthalmia-associated transcription factor positive, all melanocytic markers. The melanophages but not the tumor cells were CD68 positive, a histiocytic marker. Conclusions: The results from biopsying an episcleral nodule can help to select among therapeutic options in managing an associated ciliary body tumor. A 1-year follow-up study and 3 sequential ultrasonographic studies in the current patient have failed to document the growth of the intraocular tumor, further confirming that it is a nevus. The excised epibulbar tumor has not recurred. C1 [Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol,Dept Ophthalmol, Boston, MA USA. [Gragoudas, Evangelos S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA. [Colby, Kathryn A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 11 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD AUG PY 2013 VL 32 IS 8 BP 1174 EP 1177 DI 10.1097/ICO.0b013e31829131f8 PG 4 WC Ophthalmology SC Ophthalmology GA 187JN UT WOS:000322114000024 PM 23676784 ER PT J AU Tjora, E Wathle, G Erchinger, F Engjom, T Molven, A Aksnes, L Haldorsen, IS Dimcevski, G Raeder, H Njolstad, PR AF Tjora, E. Wathle, G. Erchinger, F. Engjom, T. Molven, A. Aksnes, L. Haldorsen, I. S. Dimcevski, G. Raeder, H. Njolstad, P. R. TI Exocrine pancreatic function in hepatocyte nuclear factor 1 beta-maturity-onset diabetes of the young (HNF1B-MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas SO DIABETIC MEDICINE LA English DT Article ID FACTOR-1-BETA MUTATIONS; SECRETIN; INSUFFICIENCY; DISEASE; QUANTIFICATION; OSTEOPOROSIS; MRCP AB Objectives To examine the exocrine pancreatic function in carriers of the hepatocyte nuclear factor 1 beta gene ( HNF1B) mutation by direct testing. Methods Patients with HNF1B mutations and control subjects were assessed using rapid endoscopic secretin tests and secretin-stimulated magnetic resonance imaging. Seven patients and 25 controls underwent endoscopy, while eight patients and 20 controls had magnetic resonance imaging. Ductal function was assessed according to peak bicarbonate concentrations and acinar function was assessed according to peak digestive enzyme activities in secretin-stimulated duodenal juice. The association of pancreatic exocrine function and diabetes status with pancreatic gland volume was examined. Results The mean increase in secretin-stimulated duodenal fluid was smaller in patients than controls ( 4.0 vs 6.4 ml/min; P = 0.003). We found lower ductal function in patients than controls ( median peak bicarbonate concentration: 73 vs 116 mEq/L; P < 0.001) and lower acinar function ( median peak lipase activity: 6.4 vs 33.5 kU/ml; P = 0.01; median peak elastase activity: 0.056 vs 0.130 U/ml; P = 0.01). Pancreatic fluid volume outputs correlated significantly with pancreatic gland volumes ( r(2) = 0.71, P = 0.008) in patients. The total fluid output to pancreatic gland volume ratios were higher in patients than controls ( 4.5 vs 1.3 ml/cm(3); P = 0.03), suggesting compensatory hypersecretion in the remaining gland. Conclusion Carriers of the HNF1B mutation have lower exocrine pancreatic function involving both ductal and acinar cells. Compensatory hypersecretion suggests that the small pancreas of HNF1B mutation carriers is attributable to hypoplasia, not atrophy. C1 [Tjora, E.; Molven, A.; Aksnes, L.; Raeder, H.; Njolstad, P. R.] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. [Tjora, E.; Aksnes, L.; Raeder, H.; Njolstad, P. R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Wathle, G.; Haldorsen, I. S.] Haukeland Hosp, Dept Radiol, N-5021 Bergen, Norway. [Erchinger, F.] Haukeland Hosp, Voss Hosp, N-5021 Bergen, Norway. [Engjom, T.; Dimcevski, G.] Haukeland Hosp, Dept Med, N-5021 Bergen, Norway. [Molven, A.; Haldorsen, I. S.] Univ Bergen, Dept Clin Med, Bergen, Norway. [Molven, A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Njolstad, P. R.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Njolstad, PR (reprint author), Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. EM pal.njolstad@uib.no OI Haldorsen, Ingfrid S./0000-0001-9313-7564 FU Western Norway Regional Health Authority; University of Bergen; Hauke-land University Hospital; Innovest; Norwegian Research Council; Novo Nordisk Foundation; K.G. Jebsen Foundation; European Research Council AdG FX Western Norway Regional Health Authority (E.T., H.R., P.R.N.), University of Bergen (A.M., L.A., P.R.N.), Hauke-land University Hospital (E.T., G.W., T.E., F.E., I.S.H., G.D., P.R.N.), Innovest (G.W., A.M., P.R.N.), Norwegian Research Council (P.R.N.), Novo Nordisk Foundation (P.R.N.), K.G. Jebsen Foundation (A.M., P.R.N.), European Research Council AdG (P.R.N.). NR 30 TC 11 Z9 11 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD AUG PY 2013 VL 30 IS 8 BP 946 EP 955 DI 10.1111/dme.12190 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 183VB UT WOS:000321844200012 PM 23600988 ER PT J AU Joshi, G Biederman, J Wozniak, J Goldin, RL Crowley, D Furtak, S Lukas, SE Gonenc, A AF Joshi, Gagan Biederman, Joseph Wozniak, Janet Goldin, Rachel L. Crowley, Dave Furtak, Stephannie Lukas, Scott E. Goenenc, Atilla TI Magnetic resonance spectroscopy study of the glutamatergic system in adolescent males with high-functioning autistic disorder: a pilot study at 4T SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Autistic disorder; Youth; Magnetic resonance spectroscopy; Glutamate ID RAT PREFRONTAL CORTEX; ASPARTATE RELEASE; CHILDHOOD AUTISM; EVOKED GLUTAMATE; YOUNG-CHILDREN; PARIETAL; AMYGDALA; GENE; MRI; ASSOCIATION AB The pilot study aimed at examining the neural glutamatergic activity in autism. Seven adolescent males (mean age: 14 +/- A 1.8; age range: 12-17 years) with intact intellectual capacity (mean IQ: 108 +/- A 14.26; IQ range: 85-127) suffering from autistic disorder and an equal number of age- and sex-matched healthy controls underwent a two-dimensional magnetic resonance spectroscopy scan at 4T. Results indicated significantly high glutamate (Glu) levels in the anterior cingulate cortex of autistic disorder versus control subjects (paired t test p = 0.01) and a trend for lower Glu in the right medial temporal lobe, which was not statistically different between the groups (paired t test p = 0.06). These preliminary findings support the glutamatergic dysregulation hypothesis in autism and need to be replicated in a larger sample. C1 [Joshi, Gagan; Biederman, Joseph; Wozniak, Janet; Goldin, Rachel L.; Furtak, Stephannie] Massachusetts Gen Hosp, Pediat Psychopharmacol Clin & Res Program, Boston, MA 02114 USA. [Joshi, Gagan; Biederman, Joseph; Wozniak, Janet; Crowley, Dave; Lukas, Scott E.; Goenenc, Atilla] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Crowley, Dave; Lukas, Scott E.; Goenenc, Atilla] McLean Hosp, McLean Imaging Ctr, Belmont, MA 02478 USA. [Lukas, Scott E.] McLean Hosp, Behav Psychopharmacol Res Lab, Belmont, MA 02478 USA. RP Joshi, G (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Clin & Res Program, 55 Fruit St,YAW 6900, Boston, MA 02114 USA. EM Joshi.Gagan@MGH.Harvard.edu; Biederman@Helix.MGH.Harvard.edu; JWozniak@partners.org; RGoldin@partners.org; DJCrowley@McLean.Harvard.edu; sfurtak1@partners.org; SLukas@McLean.Harvard.edu; agonenc@partners.org OI Crowley, David/0000-0001-9770-4482 FU Pediatric Psychopharmacology Council Fund; Norma Fine Pediatric Psychopharmacology Fellowship Fund FX This work was supported by the Pediatric Psychopharmacology Council Fund and the Norma Fine Pediatric Psychopharmacology Fellowship Fund. NR 35 TC 20 Z9 20 U1 4 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD AUG PY 2013 VL 263 IS 5 BP 379 EP 384 DI 10.1007/s00406-012-0369-9 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 192XY UT WOS:000322522500003 PM 22986449 ER PT J AU Sonnenberg, A Boardman, CR AF Sonnenberg, Amnon Boardman, Charles R. TI How to review SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2013 VL 78 IS 2 BP 343 EP 345 DI 10.1016/j.gie.2013.01.031 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 183OC UT WOS:000321825200020 PM 23867375 ER PT J AU Larson, ER Feldman, MD Valvano, JW Pearce, JA AF Larson, Erik R. Feldman, Marc D. Valvano, Jonathan W. Pearce, John A. TI Analysis of the Spatial Sensitivity of Conductance/Admittance Catheter Ventricular Volume Estimation SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Conductivity; conductance catheter; permittivity; sensitivity; tetrapolar ID PARALLEL CONDUCTANCE; DIELECTRIC-PROPERTIES; SYSTEM AB Conductance catheters are known to have a nonuniform spatial sensitivity due to the distribution of the electric field. The Geselowitz relation is applied to murine and multisegment conductance catheters using finite element models to determine the spatial sensitivity in a uniform medium and simplified left ventricle models. A new formulation is proposed that allows determination of the spatial sensitivity to admittance. Analysis of FEM numerical modeling results using the Geselowitz relation provides a true measure of parallel conductance in simplified left ventricle models for assessment of the admittance method and hypertonic saline techniques. The spatial sensitivity of blood conductance (G(b)) is determined throughout the cardiac cycle. G(b) is converted to volume using Wei's equation to determine if the presence of myocardium alters the nonlinear relationship through changes to the electric field. Results show that muscle conductance (G(m)) from the admittance method matches results from the Geselowitz relation and that the relationship between G(b) and volume is accurately fit using Wei's equation. Single-segment admittance measurements in large animals result in a more evenly distributed sensitivity to the LV blood pool. The hypertonic saline method overestimates parallel conductance throughout the cardiac cycle in both murine and multisegment conductance catheters. C1 [Larson, Erik R.; Valvano, Jonathan W.; Pearce, John A.] Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA. [Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Feldman, Marc D.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Larson, ER (reprint author), Windmill Cardiovasc Syst, Austin, TX 78752 USA. EM Larson@ece.utexas.edu; feldmanm@uthscsa.edu; valvano@mail.utexas.edu; jpearce@mail.utexas.edu FU TLL Temple Foundation; South Texas Veterans Health Care System, San Antonio, TX, USA; Scisense Systems Inc., London, ON, Canada; Admittance Technologies, Inc. FX This work was supported in part by the TLL Temple Foundation, in part by the South Texas Veterans Health Care System, San Antonio, TX, USA, and in part by Scisense Systems Inc., London, ON, Canada. The work of Dr. M. D. Feldman, Dr. J. W. Valvano, and Dr. J. A. Pearce was supported by Admittance Technologies, Inc. Asterisk indicates corresponding author. NR 17 TC 0 Z9 0 U1 1 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD AUG PY 2013 VL 60 IS 8 BP 2316 EP 2324 DI 10.1109/TBME.2013.2256134 PG 9 WC Engineering, Biomedical SC Engineering GA 186ER UT WOS:000322025300029 PM 23559022 ER PT J AU Rigg, KK Murphy, JW AF Rigg, Khary K. Murphy, John W. TI Storylines as a Neglected Tool for Mental Health Service Providers and Researchers SO INTERNATIONAL JOURNAL OF MENTAL HEALTH AND ADDICTION LA English DT Article DE Mental health practice and research; Etiology; Storylines; Community-based approach; Risk and protective factors ID PARTICIPATORY RESEARCH; SOCIAL-INDICATORS; RISK-FACTORS; MODEL; DEPRESSION; RELEVANCE; ILLNESS AB Mental health service providers and researchers usually explain psychological/behavioral problems in terms of risk and protective factors. Although such an approach may seem empirical, and thus accurate, the manner in which patients interpret these factors is often overlooked. The result is that practitioners and researchers draw conclusions and make possible causal attributions that do not take into account the perspective of those who are studied or in care. Storylines, however, are a promising strategy to understanding mental health problems that is sensitive to the experiences and situations of people, and can bring into view more relevant details of patients' lives. This paper provides a theoretically grounded justification for the use of storylines in both mental health practice and research. Storylines are defined, while suggestions are provided for how this framework might be put into practice. A discussion is offered on how storylines might improve the design and implementation of health interventions by requiring these services to become more attuned to the lived experience of patients and the meanings they attach to common risk factors. C1 [Rigg, Khary K.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Rigg, Khary K.] Univ Penn, Penn Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Murphy, John W.] Univ Miami, Dept Sociol, Coral Gables, FL 33124 USA. RP Rigg, KK (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 4100 Chester Ave,Suite 202, Philadelphia, PA USA. EM kharyrigg@gmail.com FU Veterans Affairs Advanced Fellowship Program in Health Services Research Development FX Manuscript preparation was supported, in part, by funding received through the Veterans Affairs Advanced Fellowship Program in Health Services Research & Development. NR 49 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1874 J9 INT J MENT HEALTH AD JI Int. J. Mental Health Addict. PD AUG PY 2013 VL 11 IS 4 BP 431 EP 440 DI 10.1007/s11469-012-9426-x PG 10 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA 189DJ UT WOS:000322247000003 ER PT J AU Robins, HI O'Neill, A Mehta, M Grossman, S AF Robins, H. Ian O'Neill, Anne Mehta, Minesh Grossman, Stuart TI A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT & SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 [Robins, H. Ian] Univ Wisconsin, Carbone Canc Ctr, ECOG ACRIN Canc Res Grp, Madison, WI 53706 USA. [O'Neill, Anne] Dana Farber Canc Inst, Dept Biostat & Computat Biol, ECOG ACRIN Canc Res Grp, Boston, MA 02115 USA. [Mehta, Minesh] Univ Maryland, ECOG ACRIN Canc Res Grp, Baltimore, MD 21201 USA. [Grossman, Stuart] Johns Hopkins Canc Ctr, ECOG ACRIN Canc Res Grp, Baltimore, MD USA. RP Robins, HI (reprint author), Univ Wisconsin, Carbone Canc Ctr, ECOG ACRIN Canc Res Grp, Madison, WI 53706 USA. FU NCI NIH HHS [P30 CA006973] NR 4 TC 4 Z9 5 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 AUG 1 PY 2013 VL 86 IS 5 BP 809 EP 810 DI 10.1016/j.ijrobp.2013.03.040 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 182LI UT WOS:000321743600004 PM 23845832 ER PT J AU Bortfeld, T Marks, LB AF Bortfeld, Thomas Marks, Lawrence B. TI Hype Cycle in Radiation Oncology SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID HYPERFRACTIONATED ACCELERATED RADIOTHERAPY; CELL LUNG-CANCER C1 [Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Marks, Lawrence B.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. EM tbortfeld@partners.org NR 8 TC 2 Z9 2 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2013 VL 86 IS 5 BP 819 EP 821 DI 10.1016/j.ijrobp.2013.03.027 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 182LI UT WOS:000321743600011 PM 23845838 ER PT J AU Chinnaiyan, P Won, M Wen, PY Rojiani, AM Wendland, M Dipetrillo, TA Corn, BW Mehta, MP AF Chinnaiyan, Prakash Won, Minhee Wen, Patrick Y. Rojiani, Amyn M. Wendland, Merideth Dipetrillo, Thomas A. Corn, Benjamin W. Mehta, Minesh P. TI RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID MAMMALIAN TARGET; RAPAMYCIN; PATHWAY; TRIAL; CANCER; INHIBITION; MULTIFORME; CARCINOMA; EFFICACY; GLIOMAS AB Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m(2) per day). Everolimus was escalated from2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m(2) on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established daily dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response. (C) 2013 Elsevier Inc. C1 [Chinnaiyan, Prakash] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Radiat Oncol Expt Therapeut & Canc Imaging &, Tampa, FL 33682 USA. [Won, Minhee] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Rojiani, Amyn M.] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. [Wendland, Merideth] US Oncol Willamette Valley Canc Inst, Eugene, OR USA. [Dipetrillo, Thomas A.] Rhode Isl Hosp, Dept Radiat Oncol, Providence, RI USA. [Corn, Benjamin W.] Tel Aviv Med Ctr & Sch Med, Dept Radiat Oncol, Tel Aviv, Israel. [Mehta, Minesh P.] Univ Maryland, Dept Radiat Oncol, Baltimore, MD 21201 USA. RP Chinnaiyan, P (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol & Expt Therapeut, SRB3,12902 Magnolia Dr, Tampa, FL 33612 USA. EM prakash.chinnaiyan@moffitt.org OI mehta, minesh/0000-0002-4812-5713 FU Radiation Therapy Oncology Group [U10 CA21661]; Community Clinical Oncology Program grant National Cancer Institute [U10 CA37422]; Novartis Pharmaceuticals FX This trial was conducted by the Radiation Therapy Oncology Group and was supported by Radiation Therapy Oncology Group grant U10 CA21661, Community Clinical Oncology Program grant U10 CA37422 from the National Cancer Institute, and Novartis Pharmaceuticals. This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 21 TC 29 Z9 31 U1 3 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 AUG 1 PY 2013 VL 86 IS 5 BP 880 EP 884 DI 10.1016/j.ijrobp.2013.04.036 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 182LI UT WOS:000321743600021 PM 23725999 ER PT J AU Kim, KW Ramaiya, NH Krajewski, KM Jagannathan, JP Tirumani, H Srivastava, A Ibrahim, N AF Kim, Kyung Won Ramaiya, Nikhil H. Krajewski, Katherine M. Jagannathan, Jyothi P. Tirumani, Harsha Srivastava, Amitabh Ibrahim, Nageatte TI Ipilimumab associated hepatitis: imaging and clinicopathologic findings SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Ipilimumab; Hepatitis; Immune-related adverse events; Imaging; Pathology ID METASTATIC MELANOMA; ADVERSE EVENTS; IMMUNOTHERAPY; THERAPY AB Ipilimumab is a novel immunomodulator demonstrating promising efficacy in treatment of melanoma and other cancers. The clinical benefit from ipilimumab can be hampered by the immure-related adverse events (irAEs) caused by dysregulation of host immune system. Ipilimumab associated hepatitis is also an important irAE, however, there have been limited descriptions of its clinicopathologic and imaging characteristics. We aim to describe the clinicopathologic and imaging characteristics of 6 patients who were diagnosed as ipilimumab associated hepatitis during the ipilimumab treatment for melanoma. The clinical features of these patients were as follows: (1) severe cases with systemic symptoms and highly increased level of liver function tests (LFTs), and (2) mild asymptomatic cases with mildly increased level of LFTs. In severe cases with ALT > 1,000 IU/L, imaging findings were characterized by mild hepatomegaly, periportal edema, and periportal lymphadenopathy, while mild cases showed normal imaging findings. This spectrum of imaging findings in our series was similar to that of common causes of acute hepatitis. Among 3 cases with pathologic specimen, two cases showed severe panlobular hepatitis with prominent perivenular infiltrate with endothelialitis, suggestive of predominant injury to hepatocytes, while the other case showed mild portal mononuclear infiltrate around proliferated bile ductules, suggestive of predominant injury to bile ducts. In summary, ipilimumab associated hepatitis may demonstrate variable imaging findings according to its clinical severity, and histologically may manifest either as a predominant injury to hepatocytes (acute hepatitis pattern) or as a predominant injury to bile ducts (biliary pattern). C1 [Kim, Kyung Won; Ramaiya, Nikhil H.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Tirumani, Harsha] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Srivastava, Amitabh] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ibrahim, Nageatte] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Oncol, 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. 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 13 TC 29 Z9 29 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD AUG PY 2013 VL 31 IS 4 BP 1071 EP 1077 DI 10.1007/s10637-013-9939-6 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 190IT UT WOS:000322333600030 PM 23408334 ER PT J AU Palilla, DS Alston, TA AF Palilla, David S. Alston, Theodore A. TI Reflections on an Electrocardiogram: Inverted T Waves SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Editorial Material DE electrocardiogram; filter; myocardial ischemia C1 [Palilla, David S.; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Palilla, DS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM dpalillamd@gmail.com NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD AUG PY 2013 VL 27 IS 4 BP 819 EP 820 DI 10.1053/j.jvca.2012.03.016 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 191MW UT WOS:000322418200032 PM 22560065 ER PT J AU Herbert, MR Buckley, JA AF Herbert, Martha R. Buckley, Julie A. TI Autism and Dietary Therapy: Case Report and Review of the Literature SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE autism; dietary therapy; ketogenic diet ID SPECTRUM DISORDERS; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; CELIAC-DISEASE; KETOGENIC DIET; ANTIEPILEPTIC DRUGS; EPILEPTIC SEIZURES; GUT MICROBIOME; FOOD ALLERGY; REDOX STATUS AB We report the history of a child with autism and epilepsy who, after limited response to other interventions following her regression into autism, was placed on a gluten-free, casein-free diet, after which she showed marked improvement in autistic and medical symptoms. Subsequently, following pubertal onset of seizures and after failing to achieve full seizure control pharmacologically she was advanced to a ketogenic diet that was customized to continue the gluten-free, casein-free regimen. On this diet, while still continuing on anticonvulsants, she showed significant improvement in seizure activity. This gluten-free casein-free ketogenic diet used medium-chain triglycerides rather than butter and cream as its primary source of fat. Medium-chain triglycerides are known to be highly ketogenic, and this allowed the use of a lower ratio (1.5:1) leaving more calories available for consumption of vegetables with their associated health benefits. Secondary benefits included resolution of morbid obesity and improvement of cognitive and behavioral features. Over the course of several years following her initial diagnosis, the child's Childhood Autism Rating Scale score decreased from 49 to 17, representing a change from severe autism to nonautistic, and her intelligence quotient increased 70 points. The initial electroencephalogram after seizure onset showed lengthy 3Hz spike-wave activity; 14 months after the initiation of the diet the child was essentially seizure free and the electroencephalogram showed only occasional 1-1.5 second spike-wave activity without clinical accompaniments. C1 [Herbert, Martha R.] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Herbert, Martha R.] Massachusetts Gen Hosp, TRANSCEND Res, Boston, MA 02129 USA. [Buckley, Julie A.] Pediat Partners Ponte Vedra, Ponte Vedra Beach, FL USA. [Buckley, Julie A.] Nova SE Univ, Ft Lauderdale, FL 33314 USA. RP Herbert, MR (reprint author), Massachusetts Gen Hosp, TRANSCEND Res, Boston, MA 02129 USA. EM marthaherbertmd@gmail.com NR 87 TC 15 Z9 18 U1 6 U2 118 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD AUG PY 2013 VL 28 IS 8 BP 975 EP 982 DI 10.1177/0883073813488668 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 188MW UT WOS:000322198100003 PM 23666039 ER PT J AU Paganoni, S Wills, AM AF Paganoni, Sabrina Wills, Anne-Marie TI High-Fat and Ketogenic Diets in Amyotrophic Lateral Sclerosis SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE ketogenic; fat; diet; amyotrophic lateral sclerosis; ALS ID BODY-MASS INDEX; NUTRITIONAL-STATUS; ALS PATIENTS; AXONAL GROWTH; VITAMIN-E; MANAGEMENT; SURVIVAL; BENEFIT; RISK; HYPERMETABOLISM AB Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials. C1 [Paganoni, Sabrina; Wills, Anne-Marie] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Paganoni, Sabrina; Wills, Anne-Marie] Harvard Univ, Sch Med, Boston, MA USA. [Paganoni, Sabrina] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. RP Wills, AM (reprint author), Massachusetts Gen Hosp, Wang ACC 835,15 Parkman St, Boston, MA 02114 USA. EM awills@partners.org FU Rehabilitation Medicine Scientist Training Program [2K12HD001097-16]; NINDS/NIH; Muscular Dystrophy Association; Merck Sharp and Dohme Corp.; Asubio Pharmaceuticals; NanoDerma Ltd; Accordant Health Services FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Sabrina Paganoni is funded by the Rehabilitation Medicine Scientist Training Program (grant 2K12HD001097-16). Dr Wills receives research support from the NINDS/NIH, the Muscular Dystrophy Association, and Merck Sharp and Dohme Corp. and receives consultant payments from Asubio Pharmaceuticals, NanoDerma Ltd, and Accordant Health Services. NR 38 TC 3 Z9 4 U1 4 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD AUG PY 2013 VL 28 IS 8 BP 989 EP 992 DI 10.1177/0883073813488669 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 188MW UT WOS:000322198100005 PM 23666040 ER PT J AU Danial, NN Hartman, AL Stafstrom, CE Thio, LL AF Danial, Nika N. Hartman, Adam L. Stafstrom, Carl E. Thio, Liu Lin TI How Does the Ketogenic Diet Work? Four Potential Mechanisms SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE ketogenic diet; mechanism of action; glucose; ATP-sensitive K channel; mammalian target of rapamycin; vesicular glutamate transporters; Seizure; epilepsy ID TUBEROUS SCLEROSIS COMPLEX; TEMPORAL-LOBE EPILEPSY; RAPAMYCIN SIGNALING PATHWAY; MODIFIED ATKINS DIET; MAMMALIAN TARGET; MOUSE MODEL; CHILDHOOD EPILEPSY; ANTICONVULSANT ACTIVITY; SYNAPTIC-TRANSMISSION; CALORIE RESTRICTION AB The ketogenic diet and its newer variants are clinically useful in treating epilepsy. They can also have antiepileptogenic properties and can eventually have a role in treating other neurologic and nonneurologic conditions. Despite being nearly a century old, identifying the molecular underpinnings of the ketogenic diet has been challenging. However, recent studies provide experimental evidence for 4 distinct mechanisms that could contribute to the antiseizure and other beneficial effects of these diets. These mechanisms include carbohydrate reduction, activation of adenosine triphosphate (ATP)-sensitive potassium channels by mitochondrial metabolism, inhibition of the mammalian target of rapamycin pathway, and inhibition of glutamatergic excitatory synaptic transmission. C1 [Danial, Nika N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Danial, Nika N.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Hartman, Adam L.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Hartman, Adam L.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Stafstrom, Carl E.] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. [Stafstrom, Carl E.] Univ Wisconsin, Dept Pediat, Madison, WI USA. [Thio, Liu Lin] Washington Univ, Dept Neurol, St Louis, MO 63110 USA. [Thio, Liu Lin] Washington Univ, Dept Pediat, St Louis, MO 63110 USA. [Thio, Liu Lin] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Thio, LL (reprint author), Washington Univ, Dept Neurol, 660 South Euclid Ave,Campus Box 8111, St Louis, MO 63110 USA. EM thiol@neuro.wustl.edu FU Johns Hopkins University School of Medicine; [K08NS070931] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NND, CES, and LLT received no financial support for the research, authorship, and/or publication of this article. ALH received support from K08NS070931 and a Clinician Scientist Award from the Johns Hopkins University School of Medicine. NR 70 TC 32 Z9 36 U1 3 U2 35 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD AUG PY 2013 VL 28 IS 8 BP 1027 EP 1033 DI 10.1177/0883073813487598 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 188MW UT WOS:000322198100010 PM 23670253 ER PT J AU Thiele, EA AF Thiele, Elizabeth A. TI Implications of Dietary Therapy Into the 21st Century: Conclusion to Special Issue SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE ketogenic diet; low glycemic index treatment; epilepsy AB The concept of dietary therapy for epilepsy has played an important role in the approach to the treatment of seizures for centuriesparticularly with the development and utilization of the classic ketogenic diet over the past 90 years. Recently, there has been developing interest in the utilization of diet in other medical disorders, including autism spectrum disorders, traumatic brain injury, degenerative neurologic disorders, and cancer. As the utilization of dietary therapy expands, there are several issues that need to be addressed and better characterized to better understand the role of diet in the treatment of epilepsy and other disease. C1 [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, MGH Ctr Dietary Therapy Epilepsy, Pediat Epilepsy Program, Boston, MA 02114 USA. [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Pediat, MGH Ctr Dietary Therapy Epilepsy, Pediat Epilepsy Program, Boston, MA 02114 USA. RP Thiele, EA (reprint author), 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD AUG PY 2013 VL 28 IS 8 BP 1054 EP 1055 DI 10.1177/0883073813488827 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 188MW UT WOS:000322198100016 PM 23666037 ER PT J AU Basile, JN Bloch, MJ AF Basile, Jan N. Bloch, Michael J. TI Analysis of Recent Papers in Hypertension Initial Combination Therapy Provides More Prompt Blood Pressure Control and Reduces Cardiovascular Events But Remains Underutilized SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID RISK C1 [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Seinsheimer Cardiovasc Hlth Program, Charleston, SC 29425 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Vasc Div, Renown Inst Heart & Vasc Hlth, Reno, NV 89557 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. RP Bloch, MJ (reprint author), Univ Hlth Syst, 1500 East 2nd St,Suite 302, Reno, NV 89502 USA. EM michael@bluesprucemed.com NR 7 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD AUG PY 2013 VL 15 IS 8 BP 523 EP 525 DI 10.1111/jch.12124 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188JG UT WOS:000322188700001 PM 23889711 ER PT J AU Sands-Lincoln, M Grandner, M Whinnery, J Keenan, BT Jackson, N Gurubhagavatula, I AF Sands-Lincoln, Megan Grandner, Michael Whinnery, Julia Keenan, Brendan T. Jackson, Nick Gurubhagavatula, Indira TI The Association Between Obstructive Sleep Apnea and Hypertension by Race/Ethnicity in a Nationally Representative Sample SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID POSITIVE AIRWAY PRESSURE; RISK-FACTOR; BLOOD-PRESSURE; HEART HEALTH; CARDIOVASCULAR-DISEASE; CLINICAL PRESENTATION; ADULTS; MEN; POPULATION; PREVALENCE AB The association between obstructive sleep apnea (OSA) and hypertension by race/ethnicity has not been well characterized in a national sample. Adult participants in the 2007-2008 National Health and Nutrition Examination Survey were reviewed by self-report of sleep apnea diagnosis, snorting, gasping or stopping breathing during sleep, and snoring to derive whether OSA was probable (pOSA). Multivariable logistic regression determined whether pOSA predicted hypertension in the overall cohort, and by body mass index (BMI) group and ethno-racial strata. pOSA predicted hypertension in several groups: (1) Within BMI strata, there was a significant association among overweight individuals [odds ratio [OR], 1.82; 95% confidence interval [CI], 1.26-2.62); (2) In race/ethnicity subgroups, the association was significant among Hispanic/Latinos (OR, 1.69; 95% CI, 1.13-2.53) and whites (OR, 1.40; 95% CI, 1.07-1.84); (3) In models stratified by both race/ethnicity and BMI, pOSA predicted hypertension among overweight black/African Americans (OR, 4.74; 95% CI, 1.86-12.03), overweight whites (OR, 1.65; 95% CI, 1.06-2.57), and obese Hispanic/Latino participants (OR, 2.01; 95% CI, 1.16-3.49). A simple, self-report tool for OSA was strongly associated with hypertension, and may serve as a potential future opportunity for OSA diagnosis. (C)2013 Wiley Periodicals, Inc. C1 [Sands-Lincoln, Megan; Grandner, Michael; Keenan, Brendan T.; Gurubhagavatula, Indira] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Sands-Lincoln, Megan] Elsevier, Ctr Evidence Based Med, Philadelphia, PA USA. [Whinnery, Julia] Einstein Med Ctr, Div Cardiol, Philadelphia, PA USA. [Jackson, Nick] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Pulm Crit Care Sleep Sect, Philadelphia, PA USA. RP Sands-Lincoln, M (reprint author), Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM megsands@mail.med.upenn.edu FU NIH [T32HL07713-19]; American Heart Association [12SDG9180007]; National Heart, Lung, and Blood Institute [K23HL110216]; National Institute for Environmental Health Sciences [R21ES022931]; Institute for Translational Medicine and Therapeutics; Penn CTSA [UL1RR024134]; [RO1-OH009149] FX The authors report no specific funding in relation to this research and no conflicts of interest to disclose. With regards to grant funding, Dr Sands-Lincoln is supported by NIH grant T32HL07713-19; Dr Grandner was supported by the American Heart Association (12SDG9180007), the National Heart, Lung, and Blood Institute (K23HL110216), the National Institute for Environmental Health Sciences (R21ES022931), and a fellowship from the Institute for Translational Medicine and Therapeutics, funded by UL1RR024134 (Penn CTSA); and Dr Gurubhagavatula is funded by RO1-OH009149. NR 40 TC 9 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD AUG PY 2013 VL 15 IS 8 BP 593 EP 599 DI 10.1111/jch.12144 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188JG UT WOS:000322188700013 PM 23889723 ER PT J AU Jin, BJ Thiagarajah, JR Verkman, AS AF Jin, Byung-Ju Thiagarajah, Jay R. Verkman, A. S. TI Response to "Diffusion versus convection" SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Letter ID MUCUS C1 [Jin, Byung-Ju; Thiagarajah, Jay R.; Verkman, A. S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Jin, Byung-Ju; Thiagarajah, Jay R.; Verkman, A. S.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Thiagarajah, Jay R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Jin, BJ (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. FU NIDDK NIH HHS [R01 DK035124] NR 6 TC 0 Z9 0 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 2013 VL 142 IS 2 BP 173 EP 173 DI 10.1085/jgp.201311031 PG 1 WC Physiology SC Physiology GA 190VZ UT WOS:000322371900009 PM 23898009 ER PT J AU Li, C Shu, ZJ Lee, S Gupta, MB Jansson, T Nathanielsz, PW Kamat, A AF Li, Cun Shu, Zhen-Ju Lee, Shuko Gupta, Madhulika B. Jansson, Thomas Nathanielsz, Peter W. Kamat, Amrita TI Effects of maternal nutrient restriction, intrauterine growth restriction, and glucocorticoid exposure on phosphoenolpyruvate carboxykinase-1 expression in fetal baboon hepatocytes in vitro SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE dexamethasone; diabetes non-human primate; liver ID GENE-EXPRESSION; DEVELOPMENTAL ORIGINS; EXPERIMENTAL-MODELS; METABOLIC SYNDROME; PAPIO-HAMADRYAS; SMALL-INTESTINE; BLOOD-PRESSURE; LATE-GESTATION; RHESUS FETUS; LINKAGE MAP AB Background The objective of this study was to develop a cell culture system for fetal baboon hepatocytes and to test the hypotheses that (i) expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase-1 (PEPCK-1) is upregulated in hepatocytes isolated from fetuses of nutrient-restricted mothers (MNR) compared with ad libitum-fed controls (CTR), and (ii) glucocorticoids stimulate PEPCK-1 expression. Methods Hepatocytes from 0.9G CTR and MNR fetuses were isolated and cultured. PEPCK-1 protein and mRNA levels in hepatocytes were determined by Western blot and quantitative PCR, respectively. Results Fetuses of MNR mothers were intrauterine growth restricted (IUGR). Feasibility of culturing 0.9G fetal baboon hepatocytes was demonstrated. PEPCK-1 protein levels were increased in hepatocytes isolated from IUGR fetuses, and PEPCK-1 mRNA expression was stimulated by glucocorticoids in fetal hepatocytes. Conclusions Cultured fetal baboon hepatocytes that retain their in vivo phenotype provide powerful in vitro tools to investigate mechanisms that regulate normal and programmed hepatic function. C1 [Li, Cun; Jansson, Thomas; Nathanielsz, Peter W.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA. [Li, Cun; Jansson, Thomas; Nathanielsz, Peter W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Shu, Zhen-Ju; Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Shu, Zhen-Ju; Kamat, Amrita] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX USA. [Lee, Shuko; Kamat, Amrita] South Texas Vet Hlth Care Syst, Res Serv, Audie L Murphy Div, San Antonio, TX USA. [Gupta, Madhulika B.] Univ Western Ontario, Dept Pediat, London, ON N6A 3K7, Canada. [Gupta, Madhulika B.] Univ Western Ontario, Dept Biochem, London, ON, Canada. RP Kamat, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,MC 7875, San Antonio, TX 78229 USA. EM kamat@uthscsa.edu OI Nathanielsz, Peter/0000-0001-8410-6280 FU NIH [HD 21350]; American Heart Association; Kronos Longevity Research Institute; CTSA [UL1RR025767] FX We would like to acknowledge grant support from NIH grant HD 21350 (PWN), Grant-in-Aid American Heart Association Award (AK), Kronos Longevity Research Institute grant (AK) and CTSA grant UL1RR025767 (AK). NR 59 TC 6 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2013 VL 42 IS 4 BP 211 EP 219 DI 10.1111/jmp.12048 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 190VI UT WOS:000322369600006 PM 23600855 ER PT J AU Azizaddini, S Arefanian, S Redjal, N Walcott, BP Mollahoseini, R AF Azizaddini, Shahrzad Arefanian, Saeed Redjal, Navid Walcott, Brian P. Mollahoseini, Reza TI Adult acute calcific discitis confined to the nucleus pulposus in the cervical spine Case report SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE cervical spine; disc; calcium; adult; nucleus pulposus; congenital; trauma ID INTERVERTEBRAL-DISK CALCIFICATION; NATURAL-HISTORY; CHILDHOOD; CHILDREN AB Acute calcific discitis is a rare condition in the pediatric population and has been reported in only 2 instances in the adult population. This report describes a case of acute calcific discitis that uniquely presented in the adult cervical spine. A 22-year-old woman presented with the chief complaint of sudden-onset neck pain. Nonsurgical management, including nonsteroidal antiinflammatory drugs, provided moderate symptom relief. Radiography revealed nucleus pulposus calcification at the C2-3 level. Contrast-enhanced MRI did not reveal any additional abnormalities. Further nonsurgical management, including physical therapy and nonsteroidal antiinflammatory drugs, led to complete symptom relief within 6 months. Follow-up imaging demonstrated that the calcification had nearly resolved. Acute calcific discitis should be managed conservatively; the prognosis for a complete recovery is excellent. The pathophysiology of the disorder is yet to be elucidated, and the disorder is not exclusive to the pediatric population. C1 [Azizaddini, Shahrzad] Shahid Beheshti Univ Med Sci, Tehran, Iran. [Arefanian, Saeed] Univ Tehran Med Sci, Tehran, Iran. [Redjal, Navid; Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Redjal, Navid; Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA USA. [Mollahoseini, Reza] Univ Tehran Med Sci, Firoozgar Hosp, Dept Neurosurg, Tehran, Iran. RP Redjal, N (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, 55 Fruit St, Boston, MA 02114 USA. EM nredjal@partners.org NR 27 TC 2 Z9 2 U1 1 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD AUG PY 2013 VL 19 IS 2 BP 170 EP 173 DI 10.3171/2013.4.SPINE12906 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 187CO UT WOS:000322094700004 PM 23746089 ER PT J AU Giddon, DB Swann, B Donoff, RB Hertzman-Miller, R AF Giddon, Donald B. Swann, Brian Donoff, R. Bruce Hertzman-Miller, Ruth TI Dentists as Oral Physicians: The Overlooked Primary Health Care Resource SO JOURNAL OF PRIMARY PREVENTION LA English DT Article DE Health care delivery; Primary care; Oral physician; Dentistry ID INTIMATE PARTNER VIOLENCE; DOMESTIC VIOLENCE; PSYCHIATRIC-DISORDERS; PATIENTS ATTITUDES; MEDICAL CONDITIONS; RISK; EDUCATION; PATIENT; ABUSE; NEED AB The United States is currently experiencing a primary care shortage. One solution to improving health care is to increase the utilization of existing health care providers, particularly dentists, an opportunity that has been largely ignored. By employing mid-level providers for less complex procedures to deliver more accessible dental care at lower cost, dentists can redistribute tasks to their office workforce. They can then serve as oral physicians who can provide limited preventive primary care, including screening for chronic diseases, while continuing to oversee all dental care, whether provided by dentists or non-dentists. Thus, they could improve the health of the US population as well as increase access to dental care at lower cost, while partially alleviating the primary care shortage by filling a need for the screening aspects of primary care. C1 [Giddon, Donald B.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Swann, Brian] Cambridge Hlth Alliance, Cambridge, MA USA. [Swann, Brian; Donoff, R. Bruce] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Hertzman-Miller, Ruth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Giddon, DB (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 190 Longwood Ave, Boston, MA 02115 USA. EM donald_giddon@hms.harvard.edu NR 108 TC 5 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0278-095X J9 J PRIM PREV JI J. Prim. Prev. PD AUG PY 2013 VL 34 IS 4 BP 279 EP 291 DI 10.1007/s10935-013-0310-7 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 188CM UT WOS:000322169500006 PM 23728907 ER PT J AU Pierre, JF Heneghan, AF Meudt, JM Shea, MP Krueger, CG Reed, JD Kudsk, KA Shanmuganayagam, D AF Pierre, Joseph F. Heneghan, Aaron F. Meudt, Jennifer M. Shea, Michael P. Krueger, Christian G. Reed, Jess D. Kudsk, Kenneth A. Shanmuganayagam, Dhanansayan TI Parenteral nutrition increases susceptibility of ileum to invasion by E coli SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Parenteral nutrition; Enteroinvasion; Extra-intestinal pathogens; Escherichia coli; Secretory phospholipase A2; Paneth cells; Ex vivo; Polarized in vitro organ culture ID INDUCED BACTERIAL TRANSLOCATION; HUMAN INTESTINAL-MUCOSA; GUT-DERIVED SEPSIS; PHOSPHOLIPASE A(2); PSEUDOMONAS-AERUGINOSA; SEPTIC COMPLICATIONS; SURGICAL-PATIENTS; LYMPHOID-TISSUE; PANETH CELL; DEFENSINS AB Background: Parenteral nutrition (PN), with the lack of enteral feeding, compromises mucosal immune function and increases the risk of infections. We developed an ex vivo intestinal segment culture (EVISC) model to study the ex vivo effects of PN on susceptibility of the ileum to invasion by extra-intestinal pathogenic Escherichia coli (ExPEC) and on ileal secretion of antimicrobial secretory phospholipase A(2) (sPLA(2)) in response to the pathogen. Materials and methods: Study 1: Using mouse (n = 7) ileal tissue, we examined the effects of ileal region (proximal versus distal) and varying ExPEC inoculum concentrations on ex vivo susceptibility to ExPEC invasion and sPLA(2) secretion. Study 2: Ten mice were randomized to oral chow or intravenous PN feeding for 5 d (n = 5/group). Using the EVISC model, we compared the susceptibility of ileal tissue to invasion by ExPEC and sPLA(2) secretion in response to the pathogen. Results: Study 1: The proximal ileum was more susceptible to invasion (P < 0.0001) and secreted lower amounts of sPLA(2) (P = 0.0002) than the distal ileum. Study 2: Ileal tissue from PN-fed animals was more susceptible (approximately 4-fold, P = 0.018) to invasion than those from chow-fed animals. Ileal tissue from PN-fed animals secreted less sPLA(2) (P < 0.02) than those from chow-fed animals. Conclusions: The data illustrate EVISC as a reproducible model for studying host-pathogen interactions and the effects of diet on susceptibility to infections. Specifically, the findings support our hypothesis that PN with the lack of enteral feeding decreases mucosal responsiveness to pathogen exposure and provides a plausible mechanism by which PN is associated with increased risk of infectious complication. (c) 2013 Elsevier Inc. All rights reserved. C1 [Pierre, Joseph F.; Heneghan, Aaron F.; Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Res Serv, Madison, WI USA. [Pierre, Joseph F.; Meudt, Jennifer M.; Shea, Michael P.; Krueger, Christian G.; Reed, Jess D.; Shanmuganayagam, Dhanansayan] Univ Wisconsin, Reed Res Grp, Dept Anim Sci, Madison, WI 53706 USA. [Pierre, Joseph F.; Heneghan, Aaron F.; Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI 53706 USA. RP Shanmuganayagam, D (reprint author), Univ Wisconsin, Reed Res Grp, 1675 Observ Dr,Rm 1146, Madison, WI 53706 USA. EM dshanmug@wisc.edu FU Biomedical Laboratory Research and Development Service of the VA Office of Research and Development [I01BX001672]; National Institute of Health (NIH) Grant [R01 GM53439]; Reed Research Group Multi-donor Fund FX We would like to thank Kristin M. Kohlmann for her technical assistance with bacterial culturing and preparations, and Joseph A. Heintz for his technical assistance with electron microscopy. We would also like to thank Dr. Walter J. Hopkins (Department of Urology, University of Wisconsin School of Medicine and Public Health) for providing the ExPEC Strain-5011 that was used in our studies. This project was supported by Award Number I01BX001672 from the Biomedical Laboratory Research and Development Service of the VA Office of Research and Development.; This research was also supported by National Institute of Health (NIH) Grant R01 GM53439 and the Reed Research Group Multi-donor Fund. The contents of this article do not represent the views of the Veterans Affairs or the United States Government. NR 39 TC 10 Z9 10 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2013 VL 183 IS 2 BP 583 EP 591 DI 10.1016/j.jss.2013.01.054 PG 9 WC Surgery SC Surgery GA 182JH UT WOS:000321737300020 PM 23481564 ER PT J AU Paulson, EC Fu, XY Epstein, AJ AF Paulson, Emily Carter Fu, Xiaoying Epstein, Andrew J. TI Location and timing of care for colon cancer patients in the VA Health System SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Colonic neoplasms; Coordination of care; Veteran's Health Administration; Cancer treatment ID ADJUVANT CHEMOTHERAPY; VETERANS-AFFAIRS; BREAST-CANCER; SURVIVAL; SURGERY; QUALITY; DELAY; TIME AB Background: We sought to identify colon cancer patients within the Veterans Affairs (VA) system who experienced lengthy wait times for surgery or chemotherapy. We looked specifically at the relationship between location of treatment and timing of care. Methods: We performed a retrospective cohort study of 4635 patients diagnosed with colon cancer in the VA Health System during 2002-2010 and treated with surgery followed by chemotherapy. We used VA administrative databases, including the VA Outpatient Clinic, Patient Treatment, and Fee Basis inpatient and outpatient files. Time from diagnosis to surgery and time from surgery to initiation of chemotherapy were the primary outcome measures. Results: Patients who required referral to a hospital different from their home VA facility for surgery experienced delays in surgical intervention compared with patients treated at their home VA medical center. For patients referred outside of the VA system, this delay was almost 2 wk (13.5 d, P < 0.001). When these patients then went to another hospital for chemotherapy, they experienced further delays in care. Patients treated surgically outside the VA system who returned to the VA system for chemotherapy were more likely to initiate chemo >8 wk following surgery (OR 1.69, P = 0.01). The average adjusted time from surgery to chemotherapy for these patients compared with those treated wholly within the VA system was 11.4 d (P = 0.003). Conclusions: VA patients who require treatment at multiple hospitals for colon cancer, especially those who require surgery outside of the VA system, are more likely to experience delays in care compared with patients treated at a single hospital. Published by Elsevier Inc. C1 [Paulson, Emily Carter; Fu, Xiaoying; Epstein, Andrew J.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Paulson, Emily Carter] Univ Penn, Dept Surg, Div Colon & Rectal Surg Philadelphia, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Paulson, EC (reprint author), Univ Penn, Vet Affairs Med Ctr, Dept Surg Educ, 3900 Woodland Ave PVAMC,5th Floor, Philadelphia, PA 19104 USA. EM ecp6z@yahoo.com FU Center for Health Equity Research and Promotion (CHERP), VA Pittsburgh Healthcare System/Philadelphia VA Medical Center, VISN4 VA Healthcare Network FX This research was funded by a pilot grant from the Center for Health Equity Research and Promotion (CHERP), VA Pittsburgh Healthcare System/Philadelphia VA Medical Center, VISN4 VA Healthcare Network. NR 20 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2013 VL 183 IS 2 BP 639 EP 644 DI 10.1016/j.jss.2013.02.049 PG 6 WC Surgery SC Surgery GA 182JH UT WOS:000321737300027 PM 23522460 ER PT J AU Nichols, DP Caceres, S Caverly, L Fratelli, C Kim, SH Malcolm, K Poch, KR Saavedra, M Solomon, G Taylor-Cousar, J Moskowitz, S Nick, JA AF Nichols, David P. Caceres, Silvia Caverly, Lindsay Fratelli, Cori Kim, Sun Ho Malcolm, Ken Poch, Katie R. Saavedra, Milene Solomon, George Taylor-Cousar, Jennifer Moskowitz, Samuel Nick, Jerry A. TI Effects of azithromycin in Pseudomonas aeruginosa burn wound infection SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Burn; Burn wound; Pseudomonas aeruginosa; Thermal injury; Azithromycin; Tobramycin; Ciprofloxacin; Biofilm; Drug-drug interaction; Cystic fibrosis ID RANDOMIZED CONTROLLED-TRIAL; CYSTIC-FIBROSIS; OUTER-MEMBRANE; EFFICACY; MICE; CLARITHROMYCIN; CHILDREN; THERAPY; SEPSIS; INJURY AB Background: Cutaneous thermal injuries (i.e., burns) remain a common form of debilitating trauma, and outcomes are often worsened by wound infection with environmental bacteria, chiefly Pseudomonas aeruginosa. Materials and methods: We tested the effects of early administration of a single dose of azithromycin, with or without subsequent antipseudomonal antibiotics, in a mouse model of standardized thermal injury infected with P aeruginosa via both wound site and systemic infection. We also tested the antimicrobial effects of these antibiotics alone or combined in comparative biofilm and planktonic cultures in vitro. Results: In our model, early azithromycin administration significantly reduced wound and systemic infection without altering wound site or circulating neutrophil activity. The antimicrobial effect of azithromycin was additive with ciprofloxacin but significantly reduced the antimicrobial effect of tobramycin. This pattern was reproduced in biofilm cultures and not observed in planktonic cultures of P aeruginosa. Conclusion: These data suggest that early administration of azithromycin following burn-related trauma and infection may reduce P aeruginosa infection and potential interactions with other antibiotics should be considered when designing future studies. (c) 2013 Elsevier Inc. All rights reserved. C1 [Nichols, David P.; Fratelli, Cori; Taylor-Cousar, Jennifer] Natl Jewish Hlth, Dept Pediat, Div Pulm Med, Denver, CO 80206 USA. [Nichols, David P.; Caceres, Silvia; Malcolm, Ken; Poch, Katie R.; Saavedra, Milene; Taylor-Cousar, Jennifer; Nick, Jerry A.] Natl Jewish Hlth, Dept Med, Div Pulm Med, Denver, CO 80206 USA. [Nichols, David P.; Caverly, Lindsay; Malcolm, Ken; Saavedra, Milene; Solomon, George; Taylor-Cousar, Jennifer; Nick, Jerry A.] Univ Colorado, Sch Med, Dept Med, Div Pulm & Crit Care, Aurora, CO USA. [Kim, Sun Ho; Moskowitz, Samuel] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Nichols, DP (reprint author), Natl Jewish Hlth, 1400 Jackson St,A440, Denver, CO 80206 USA. EM nicholsd@njhealth.org FU US Department of Defense [DR080371]; NIH/NCATS Colorado CTSI Grant [KL2 TR000156]; NIAID [R01AI067653]; National Institutes of Health [1R01HL090991]; Rebecca Runyon Bryan Chair for Cystic Fibrosis; Cystic Fibrosis Foundation FX This work was supported by the US Department of Defense DR080371 to J.A.N. and D.P.N., by NIH/NCATS Colorado CTSI Grant Number KL2 TR000156 to D.P.N., and by NIAID R01AI067653 to S.M.M. Support was also provided by the National Institutes of Health (1R01HL090991), the Rebecca Runyon Bryan Chair for Cystic Fibrosis, and the Cystic Fibrosis Foundation. Contents are the authors' sole responsibility and do not necessarily represent official views of the sponsors. NR 40 TC 9 Z9 9 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2013 VL 183 IS 2 BP 767 EP 776 DI 10.1016/j.jss.2013.02.003 PG 10 WC Surgery SC Surgery GA 182JH UT WOS:000321737300043 PM 23478086 ER PT J AU Crawford, RS Albadawi, H Robaldo, A Peck, MA Abularrage, CJ Yoo, HJ LaMuraglia, GM Watkins, MT AF Crawford, Robert S. Albadawi, Hassan Robaldo, Alessandro Peck, Michael A. Abularrage, Christopher J. Yoo, Hyung-Jin LaMuraglia, Glenn M. Watkins, Michael T. TI Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/- mice SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Inflammation; Ischemia; Exercise; Skeletal muscle; Reperfusion; Cytokines; Growth factors ID PERIPHERAL ARTERIAL-DISEASE; MUSCLE REPERFUSION INJURY; SKELETAL-MUSCLE; IN-VIVO; POLY(ADP-RIBOSE) POLYMERASE; MURINE MODEL; EXPRESSION; EXERCISE; ISCHEMIA/REPERFUSION; MOUSE AB Background: We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Methods: Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Results: Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P < 0.0001). After exercise, plasma levels of vascular endothelial cell growth factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P < 0.004). The cytokines KC and MIP-2 in muscle were greater in exercised ApoE-/- mice compared with C57BL6 mice (P = 0.01). Increased poly-ADP-ribose activity and mature muscle regeneration were associated with demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P 0.01). Conclusions: Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. (c) 2013 Elsevier Inc. All rights reserved. C1 [Watkins, Michael T.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, 15 Parkman St,Suite 440, Boston, MA 02114 USA. EM mtwpp@aol.com FU National Institutes of Health [1R01AR055843]; Foundation for Advanced Vascular Research; Division of Vascular and Endovascular Surgery, Massachusetts General Hospital FX The authors acknowledge funding from the National Institutes of Health (Grant 1R01AR055843), the Foundation for Advanced Vascular Research (Wylie Scholar Award), and the Division of Vascular and Endovascular Surgery, Massachusetts General Hospital (Geneen Fund). Dr. Watkins is the Isenberg Scholar in Academic Surgery at the Massachusetts General Hospital. NR 47 TC 1 Z9 2 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2013 VL 183 IS 2 BP 952 EP 962 DI 10.1016/j.jss.2013.02.042 PG 11 WC Surgery SC Surgery GA 182JH UT WOS:000321737300068 PM 23528286 ER PT J AU Nishino, M Dahlberg, SE Cardarella, S Jackman, DM Rabin, MS Hatabu, H Janne, PA Johnson, BE AF Nishino, Mizuki Dahlberg, Suzanne E. Cardarella, Stephanie Jackman, David M. Rabin, Michael S. Hatabu, Hiroto Jaenne, Pasi A. Johnson, Bruce E. TI Tumor Volume Decrease at 8 Weeks Is Associated with Longer Survival in EGFR-Mutant Advanced Non-Small-Cell Lung Cancer Patients Treated with EGFR TKI SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Computed tomography scans; Tumor volume; Epidermal growth factor receptor mutations; Epidermal growth factor receptor tyrosine kinase inhibitors ID TYROSINE KINASE INHIBITORS; GROWTH-FACTOR RECEPTOR; RESPONSE EVALUATION CRITERIA; GUIDELINE VERSION 1.1; SOLID TUMORS; ACQUIRED-RESISTANCE; 1ST-LINE TREATMENT; RADIATION-THERAPY; PROGNOSTIC-FACTOR; OPEN-LABEL AB Background: The study investigated whether tumor volume changes at 8 weeks of therapy is associated with outcomes in advanced non-small-cell lung cancer (NSCLC) patients harboring sensitizing epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs). Methods: In 56 advanced NSCLC patients with sensitizing EGFR mutations treated with first-line erlotinib or gefitinib, tumor volumes of dominant lung lesions were measured on baseline and follow-up computed tomography, and were analyzed for association with survival. Results: Among 56 eligible patients, the median tumor volume was 17.8cm(3) (range, 1.3-172.7cm(3)) on the baseline scans. Forty-nine patients had follow-up computed tomography at approximately 8 weeks; the median tumor volume at 8 weeks was 7.1cm(3) (range, 0.4-62.3cm(3)), with the median proportional volume change of -59% (range, -90% to +91%) from baseline. The proportional volume change at 8 weeks was associated with survival (p = 0.02). Using the cutoff value of 38% volume decrease (75th percentile) at 8 weeks, patients with volume decrease more than 38% (n = 37) had a median overall survival of 43.5 months compared with 16.3 months among those with volume decrease of 38% or less (n = 12; p = 0.01). The median progression-free survival for patients with more than 38% volume decrease was 12.6 months, compared with 5.5 months for those with 38% or lesser volume decrease (p = 0.2). Conclusion: The proportional volume change at 8 weeks is associated with overall survival in EGFR-mutant advanced NSCLC patients treated with first-line EGFR-TKIs. The observation of the study, if confirmed in larger study cohorts, indicates that tumor volume analysis at 8 weeks may provide an early marker for survival, and contribute to therapeutic decision making by identifying patients who may benefit from additional anticancer therapy after 8 weeks of EGFR-TKI therapy. C1 [Nishino, Mizuki] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol & Med, Boston, MA 02215 USA. [Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Jaenne, Pasi A.; Johnson, Bruce E.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Nishino, Mizuki; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. RP Nishino, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU National Cancer Institute [1K23CA157631]; National Institutes of Health [1RO1CA114465-01, 5R21 CA11627-02]; National Cancer Institute Specialized Program of Research Excellence in Lung Cancer [2P50CA090578-06]; Genentech Inc.; Doris and William Krupp Research Fund in Thoracic Oncology; American Society of Clinical Oncology Translational Research Professorship FX The investigators were supported by 1K23CA157631 (National Cancer Institute) (MN). Grants 1RO1CA114465-01 (BEJ and PAJ) and 5R21 CA11627-02 (HH), from the National Institutes of Health, Grant No. 2P50CA090578-06 (BEJ and PAJ) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc., and by the Doris and William Krupp Research Fund in Thoracic Oncology and American Society of Clinical Oncology Translational Research Professorship. David M. Jackman serves as a Consultant for Foundation Medicine and on the Advisory Board of Genentech, and has received honararium from Chugai. Pasi A. Janne serves as a Consultant for Genentech, Roche, and OSI Pharmaceuticals; and has received post-marketing royalties from DFCI owned IP on EGFR mutations. Bruce E. Johnson serves as a Consultant for Bristol Myers, Astrazeneca, Genentech, Millenium, Pfizer, Sanofi, and Chugai; and has received post-marketing royalties from DFCI for EFGR mutation testing. The other author declare no conflicts of interest. NR 55 TC 11 Z9 11 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2013 VL 8 IS 8 BP 1059 EP 1068 DI 10.1097/JTO.0b013e318294c909 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 190IZ UT WOS:000322334300017 PM 23787800 ER PT J AU Aisner, J Manola, JB Dakhil, SR Stella, PJ Sovak, MA Schiller, JH AF Aisner, Joseph Manola, Judith B. Dakhil, Shaker R. Stella, Philip J. Sovak, Mika A. Schiller, Joan H. TI Vandetanib Plus Chemotherapy for Induction Followed by Vandetanib or Placebo As Maintenance for Patients with Advanced Non-Small-Cell Lung Cancer: A Randomized Phase 2 PrECOG Study (PrE0501) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Vandetanib; Non-small-cell lung cancer; Maintenance therapy ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; DOUBLE-BLIND; 1ST-LINE TREATMENT; III TRIAL; ERLOTINIB; CARBOPLATIN; PACLITAXEL; BEVACIZUMAB; GEMCITABINE AB Introduction: After early reports of vandetanib's efficacy in the induction setting, we evaluated the effect of combination docetaxel, carboplatin, and vandetanib, followed by maintenance therapy with either vandetanib, or placebo on progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. Methods: Patients with advanced non-small-cell lung cancer were randomized to induction docetaxel (75mg/m(2)) + carboplatin (area under the curve of 6) on day 1 of a 21-day cycle, and daily vandetanib (100mg/day orally) for four cycles, followed by daily vandetanib (300mg/day orally) or placebo until progression. Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 of 1, and no prior cytotoxic or targeted agents for advanced disease. Results: One hundred sixty-two patients were randomized; 158 began induction treatment. Fifty-eight patients began maintenance vandetanib or placebo (median, 3.5 cycles). Median PFS for patients randomized to maintenance vandetanib was 4.5 months (95% confidence interval, 3.3-5.8 months), and for patients randomized to maintenance placebo was 4.2 months (95% confidence interval, 2.8-4.9 months). An exploratory analysis showed prolonged PFS for patients randomized to vandetanib maintenance (stratified log-rank p= 0.07) as also in a multivariate model adjusting for sex and stage (p= 0.02). Differences in PFS were not observed among patients who began maintenance therapy. Toxicities were similar to other studies of these agents. Conclusion: Neither arm showed improvement over historical median PFS of 4.6 months, although patients who began maintenance and were randomized to vandetanib had somewhat better outcomes than those randomized to placebo. Given its acceptable toxicity profile, there may be a role for vandetanib in maintenance. C1 [Aisner, Joseph] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med Oncol, Canc Inst New Jersey, New Brunswick, NJ USA. [Manola, Judith B.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Dakhil, Shaker R.] Canc Ctr Kansas, Dept Med Oncol, Wichita, KS USA. [Stella, Philip J.] St Joseph Mercy Hosp, Dept Med Oncol, Ann Arbor, MI 48104 USA. [Sovak, Mika A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Dept Hematol Oncol, Dallas, TX 75390 USA. RP Manola, JB (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM jmanola@jimmy.harvard.edu FU AstraZeneca Pharmaceuticals; AstraZeneca FX Research support was provided by AstraZeneca Pharmaceuticals. AstraZeneca's support for the study included financial support for the statistical analysis (J.M.). M. S. is currently employed as a medical director for Roche. J.S. has a consultant/advisory role with and research funding from AstraZeneca. NR 29 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2013 VL 8 IS 8 BP 1075 EP 1083 DI 10.1097/JTO.0b013e3182937317 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 190IZ UT WOS:000322334300019 PM 23689430 ER PT J AU Nielles-Vallespin, S Mekkaoui, C Gatehouse, P Reese, TG Keegan, J Ferreira, PF Collins, S Speier, P Feiweier, T de Silva, R Jackowski, MP Pennell, DJ Sosnovik, DE Firmin, D AF Nielles-Vallespin, Sonia Mekkaoui, Choukri Gatehouse, Peter Reese, Timothy G. Keegan, Jennifer Ferreira, Pedro F. Collins, Steve Speier, Peter Feiweier, Thorsten de Silva, Ranil Jackowski, Marcel P. Pennell, Dudley J. Sosnovik, David E. Firmin, David TI In vivo diffusion tensor MRI of the human heart: Reproducibility of breath-hold and navigator-based approaches SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cardiovascular magnetic resonance imaging; prospective navigators; cardiac diffusion tensor imaging; cardiac diffusion-weighted imaging ID RESONANCE CORONARY-ANGIOGRAPHY; CARDIAC FIBER ARCHITECTURE; MYOCARDIAL BLOOD-VOLUME; MAGNETIC-RESONANCE; HISTOLOGICAL VALIDATION; WATER DIFFUSION; LEFT-VENTRICLE; INFARCTION; MOTION; TRACTOGRAPHY AB The aim of this study was to implement a quantitative in vivo cardiac diffusion tensor imaging (DTI) technique that was robust, reproducible, and feasible to perform in patients with cardiovascular disease. A stimulated-echo single-shot echo-planar imaging (EPI) sequence with zonal excitation and parallel imaging was implemented, together with a novel modification of the prospective navigator (NAV) technique combined with a biofeedback mechanism. Ten volunteers were scanned on two different days, each time with both multiple breath-hold (MBH) and NAV multislice protocols. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) fiber maps were created. Comparison of initial and repeat scans showed good reproducibility for both MBH and NAV techniques for FA (P > 0.22), MD (P > 0.15), and HA (P > 0.28). Comparison of MBH and NAV FA (FA(MBHday1) = 0.60 +/- 0.04, FA(NAVday1) = 0.60 +/- 0.03, P = 0.57) and MD (MDMBHday1 = 0.8 +/- 0.2 x 10(-3) mm(2)/s, MDNAVday1 = 0.9 +/- 0.2 x 10(-3) mm(2)/s, P = 0.07) values showed no significant differences, while HA values (HA(MBHday1Endo) = 22 +/- 10 degrees, HA(MBHday1Mid-Endo) = 20 +/- 6 degrees, HA(MBHday1Mid-Epi) = -1 +/- 6 degrees, HA(MBHday1Epi) = -17 +/- 6 degrees, HA(NAVday1Endo) = 7 +/- 7 degrees, HA(NAVday1Mid-Endo) = 13 +/- 8 degrees, HA(NAVday1Mid-Epi) = -2 +/- 7 degrees, HA(NAVday1Epi) = -14 +/- 6 degrees) were significantly different. The scan duration was 20% longer with the NAV approach. Currently, the MBH approach is the more robust in normal volunteers. While the NAV technique still requires resolution of some bulk motion sensitivity issues, these preliminary experiments show its potential for in vivo clinical cardiac diffusion tensor imaging and for delivering high-resolution in vivo 3D DTI tractography of the heart. Magn Reson Med 70:454-465, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Nielles-Vallespin, Sonia; Gatehouse, Peter; Keegan, Jennifer; Ferreira, Pedro F.; Collins, Steve; de Silva, Ranil; Pennell, Dudley J.; Firmin, David] Royal Brompton & Harefield NHS Fdn Trust, Cardiovasc MR Unit, London, England. [Nielles-Vallespin, Sonia; Gatehouse, Peter; Keegan, Jennifer; Ferreira, Pedro F.; de Silva, Ranil; Pennell, Dudley J.; Firmin, David] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Mekkaoui, Choukri; Reese, Timothy G.; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. [Speier, Peter; Feiweier, Thorsten] Siemens AG, Healthcare Sect, MR R&D, Erlangen, Germany. [Jackowski, Marcel P.] Univ Sao Paulo, Inst Math & Stat, Sao Paulo, Brazil. RP Nielles-Vallespin, S (reprint author), Univ London Imperial Coll Sci Technol & Med, South Kensington Campus, London SW7 2AZ, England. EM s.nielles-vallespin@rbht.nhs.uk RI Jackowski, Marcel/G-7602-2012; Cesar-Jr, Roberto/I-8222-2015; OI Gatehouse, Peter/0000-0002-0260-4719 FU NIHR Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London; National Institutes of Health [R01HL093038] FX Grant sponsor: NIHR Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London; Grant sponsor: National Institutes of Health; Grant number: R01HL093038. NR 62 TC 37 Z9 39 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2013 VL 70 IS 2 BP 454 EP 465 DI 10.1002/mrm.24488 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187OL UT WOS:000322128300018 PM 23001828 ER PT J AU Anttila, V Winsvold, BS Gormley, P Kurth, T Bettella, F McMahon, G Kallela, M Malik, R de Vries, B Terwindt, G Medland, SE Todt, U McArdle, WL Quaye, L Koiranen, M Ikram, MA Lehtimaki, T Stam, AH Ligthart, L Wedenoja, J Dunham, I Neale, BM Palta, P Hamalainen, E Schurks, M Rose, LM Buring, JE Ridker, PM Steinberg, S Stefansson, H Jakobsson, F Lawlor, DA Evans, DM Ring, SM Farkkila, M Artto, V Kaunisto, MA Freilinger, T Schoenen, J Frants, RR Pelzer, N Weller, CM Zielman, R Heath, AC Madden, PAF Montgomery, GW Martin, NG Borck, G Gobel, H Heinze, A Heinze-Kuhn, K Williams, FMK Hartikainen, AL Pouta, A van den Ende, J Uitterlinden, AG Hofman, A Amin, N Hottenga, JJ Vink, JM Heikkila, K Alexander, M Muller-Myhsok, B Schreiber, S Meitinger, T Wichmann, HE Aromaa, A Eriksson, JG Traynor, BJ Trabzuni, D Rossin, E Lage, K Jacobs, SBR Gibbs, JR Birney, E Kaprio, J Penninx, BW Boomsma, DI van Duijn, C Raitakari, O Jarvelin, MR Zwart, JA Cherkas, L Strachan, DP Kubisch, C Ferrari, MD van den Maagdenberg, AMJM Dichgans, M Wessman, M Smith, GD Stefansson, K Daly, MJ Nyholt, DR Chasman, DI Palotie, A AF Anttila, Verneri Winsvold, Bendik S. Gormley, Padhraig Kurth, Tobias Bettella, Francesco McMahon, George Kallela, Mikko Malik, Rainer de Vries, Boukje Terwindt, Gisela Medland, Sarah E. Todt, Unda McArdle, Wendy L. Quaye, Lydia Koiranen, Markku Ikram, M. Arfan Lehtimaki, Terho Stam, Anine H. Ligthart, Lannie Wedenoja, Juho Dunham, Ian Neale, Benjamin M. Palta, Priit Hamalainen, Eija Schuerks, Markus Rose, Lynda M. Buring, Julie E. Ridker, Paul M. Steinberg, Stacy Stefansson, Hreinn Jakobsson, Finnbogi Lawlor, Debbie A. Evans, David M. Ring, Susan M. Farkkila, Markus Artto, Ville Kaunisto, Mari A. Freilinger, Tobias Schoenen, Jean Frants, Rune R. Pelzer, Nadine Weller, Claudia M. Zielman, Ronald Heath, Andrew C. Madden, Pamela A. F. Montgomery, Grant W. Martin, Nicholas G. Borck, Guntram Goebel, Hartmut Heinze, Axel Heinze-Kuhn, Katja Williams, Frances M. K. Hartikainen, Anna-Liisa Pouta, Anneli van den Ende, Joyce Uitterlinden, Andre G. Hofman, Albert Amin, Najaf Hottenga, Jouke-Jan Vink, Jacqueline M. Heikkila, Kauko Alexander, Michael Muller-Myhsok, Bertram Schreiber, Stefan Meitinger, Thomas Wichmann, Heinz Erich Aromaa, Arpo Eriksson, Johan G. Traynor, Bryan J. Trabzuni, Daniah Rossin, Elizabeth Lage, Kasper Jacobs, Suzanne B. R. Gibbs, J. Raphael Birney, Ewan Kaprio, Jaakko Penninx, Brenda W. Boomsma, Dorret I. van Duijn, Cornelia Raitakari, Olli Jarvelin, Marjo-Riitta Zwart, John-Anker Cherkas, Lynn Strachan, David P. Kubisch, Christian Ferrari, Michel D. van den Maagdenberg, Arn M. J. M. Dichgans, Martin Wessman, Maija Smith, George Davey Stefansson, Kari Daly, Mark J. Nyholt, Dale R. Chasman, Daniel I. Palotie, Aarno CA North Amer Brain Expression UK Brain Expression Consortium Int Headache Genetics Consortium TI Genome-wide meta-analysis identifies new susceptibility loci for migraine SO NATURE GENETICS LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; NEURITE OUTGROWTH; DOWN-REGULATION; HUMAN-DISEASE; ASSOCIATION; EXPRESSION; PROTEIN; FAMILY; PROTEOLYSIS; POPULATION AB Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 x 10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B. C1 [Anttila, Verneri; Winsvold, Bendik S.; Gormley, Padhraig; Palta, Priit; Hamalainen, Eija; Palotie, Aarno] Wellcome Trust Sanger Inst, Cambridge, England. [Anttila, Verneri; Palta, Priit; Hamalainen, Eija; Kaunisto, Mari A.; Kaprio, Jaakko; Wessman, Maija; Palotie, Aarno] Univ Helsinki, FIMM, Helsinki, Finland. [Anttila, Verneri; Neale, Benjamin M.; Rossin, Elizabeth; Lage, Kasper; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri; Kurth, Tobias; Neale, Benjamin M.; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.; Rossin, Elizabeth; Lage, Kasper; Daly, Mark J.; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA USA. [Anttila, Verneri; Neale, Benjamin M.; Rossin, Elizabeth; Lage, Kasper; Jacobs, Suzanne B. R.; Daly, Mark J.; Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Winsvold, Bendik S.; Zwart, John-Anker] Oslo Univ Hosp, Dept Neurol, Oslo, Norway. [Winsvold, Bendik S.; Zwart, John-Anker] Univ Oslo, Oslo, Norway. [Kurth, Tobias] INSERM, Neuroepidemiol U708, Bordeaux, France. [Kurth, Tobias] Univ Bordeaux, Bordeaux, France. [Kurth, Tobias; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Bettella, Francesco; Steinberg, Stacy; Stefansson, Hreinn; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [McMahon, George; McArdle, Wendy L.; Lawlor, Debbie A.; Evans, David M.; Ring, Susan M.; Smith, George Davey] Univ Bristol, Univ Bristol Med Res Council MRC Integrat Epidemi, Bristol, Avon, England. [Kallela, Mikko; Farkkila, Markus; Artto, Ville] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. [Malik, Rainer; Freilinger, Tobias; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [de Vries, Boukje; Frants, Rune R.; Weller, Claudia M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Terwindt, Gisela; Stam, Anine H.; Pelzer, Nadine; Zielman, Ronald; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [Medland, Sarah E.; Montgomery, Grant W.; Martin, Nicholas G.; Nyholt, Dale R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Todt, Unda; Borck, Guntram; Kubisch, Christian] Univ Ulm, Inst Human Genet, D-89069 Ulm, Germany. [Quaye, Lydia; Williams, Frances M. K.; Cherkas, Lynn] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Koiranen, Markku; Pouta, Anneli; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Koiranen, Markku; Pouta, Anneli; Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. [Ikram, M. Arfan; van den Ende, Joyce; Hofman, Albert; Amin, Najaf; van Duijn, Cornelia] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Ligthart, Lannie; Hottenga, Jouke-Jan; Vink, Jacqueline M.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Ligthart, Lannie; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Wedenoja, Juho; Heikkila, Kauko; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Dunham, Ian; Birney, Ewan] European Mol Biol Lab, European Bioinformat Inst, Cambridge, England. [Schuerks, Markus] Univ Hosp Essen, Dept Neurol, Essen, Germany. [Ridker, Paul M.] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. [Jakobsson, Finnbogi] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland. [Kaunisto, Mari A.; Eriksson, Johan G.; Wessman, Maija] Folkhalsan Res Ctr, Helsinki, Finland. [Freilinger, Tobias] Klinikum Univ Munchen, Dept Neurol, Munich, Germany. [Schoenen, Jean] Univ Liege, Dept Neurol, Headache Res Unit, Liege, Belgium. [Schoenen, Jean] Univ Liege, GIGA Neurosci, Liege, Belgium. [Heath, Andrew C.; Madden, Pamela A. F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Goebel, Hartmut; Heinze, Axel; Heinze-Kuhn, Katja] Kiel Pain & Headache Ctr, Kiel, Germany. [Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Hosp Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland. [Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Med Res Ctr, Oulu, Finland. [Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children Young People & Families, Helsinki, Finland. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Alexander, Michael] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Alexander, Michael] Univ Bonn, Inst Human Genet, Bonn, Germany. [Muller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Muller-Myhsok, Bertram; Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Schreiber, Stefan] Univ Kiel, Dept Internal Med 1, Kiel, Germany. [Meitinger, Thomas] Helmholtz Ctr Munich, Inst Human Genet, Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany. [Wichmann, Heinz Erich] Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany. [Wichmann, Heinz Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, Neuherberg, Germany. [Wichmann, Heinz Erich] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany. [Aromaa, Arpo; Eriksson, Johan G.] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Dept Gen Practice, Helsinki, Finland. [Eriksson, Johan G.] Vaasa Cent Hosp, Vaasa, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Traynor, Bryan J.; Gibbs, J. Raphael] NIA, Neurogenet Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Trabzuni, Daniah; Gibbs, J. Raphael] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [Rossin, Elizabeth] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lage, Kasper] Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Pediat Surg Res Labs, Boston, MA 02114 USA. [Lage, Kasper] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Lage, Kasper] Univ Copenhagen, Ctr Prot Res, Copenhagen, Denmark. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. [Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Raitakari, Olli] Univ Turku, Turku Univ Hosp, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, Sch Publ Hlth,Dept Epidemiol & Biostat, London, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England. [Stefansson, Kari] Univ Iceland, Sch Med, Reykjavik, Iceland. RP Palotie, A (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England. EM anttila@atgu.mgh.harvard.edu; ap8@sanger.ac.uk RI Nyholt, Dale/C-8384-2013; Kubisch, Christian/F-1893-2011; Traynor, Bryan/G-5690-2010; Schreiber, Stefan/B-6748-2008; Singleton, Andrew/C-3010-2009; Medland, Sarah/C-7630-2013; Borck, Guntram/F-1868-2015; Montgomery, Grant/B-7148-2008; Meitinger, Thomas/O-1318-2015; Davey Smith, George/A-7407-2013; Trabzuni, Daniah/C-4034-2012; Kurth, Tobias/A-9243-2012; Weale, Michael/F-2587-2010 OI Anttila, Verneri/0000-0002-0073-4675; Ikram, Mohammad Arfan/0000-0003-0372-8585; Gormley, Padhraig/0000-0002-8908-6968; Williams, Frances/0000-0002-2998-2744; Stefansson, Hreinn/0000-0002-9331-6666; Dunham, Ian/0000-0003-2525-5598; Birney, Ewan/0000-0001-8314-8497; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Eriksson, Johan/0000-0002-2516-2060; Evans, David/0000-0003-0663-4621; Palta, Priit/0000-0001-9320-7008; Wedenoja, Juho/0000-0002-6155-0378; Kaunisto, Mari/0000-0002-6946-9195; Kaprio, Jaakko/0000-0002-3716-2455; Lawlor, Debbie A/0000-0002-6793-2262; Winsvold, Bendik Slagsvold/0000-0003-4171-8919; Martin, Nicholas/0000-0003-4069-8020; Kubisch, Christian/0000-0003-4220-0978; Schreiber, Stefan/0000-0003-2254-7771; Medland, Sarah/0000-0003-1382-380X; Montgomery, Grant/0000-0002-4140-8139; Davey Smith, George/0000-0002-1407-8314; Trabzuni, Daniah/0000-0003-4826-9570; Kurth, Tobias/0000-0001-7169-2620; Weale, Michael/0000-0003-4593-1186 FU Intramural NIH HHS [Z01 AG000949-02]; Medical Research Council [G1001799, G9815508, G0802462, MC_UU_12013/1, MC_UU_12013/4, MC_UU_12013/5]; NIAAA NIH HHS [K05 AA017688]; NIGMS NIH HHS [T32 GM007753]; Wellcome Trust [089062, 092731] NR 52 TC 119 Z9 119 U1 6 U2 53 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 AUG PY 2013 VL 45 IS 8 BP 912 EP U255 DI 10.1038/ng.2676 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 190WW UT WOS:000322374900015 PM 23793025 ER PT J AU Jones, DTW Hutter, B Jager, N Korshunov, A Kool, M Warnatz, HJ Zichner, T Lambert, SR Ryzhova, M Quang, DAK Fontebasso, AM Stutz, AM Hutter, S Zuckermann, M Sturm, D Gronych, J Lasitschka, B Schmidt, S Seker-Cin, H Witt, H Sultan, M Ralser, M Northcott, PA Hovestadt, V Bender, S Pfaff, E Stark, S Faury, D Schwartzentruber, J Majewski, J Weber, UD Zapatka, M Raeder, B Schlesner, M Worth, CL Bartholomae, CC von Kalle, C Imbusch, CD Radomski, S Lawerenz, C van Sluis, P Koster, J Volckmann, R Versteeg, R Lehrach, H Monoranu, C Winkler, B Unterberg, A Herold-Mende, C Milde, T Kulozik, AE Ebinger, M Schuhmann, MU Cho, YJ Pomeroy, SL von Deimling, A Witt, O Taylor, MD Wolf, S Karajannis, MA Eberhart, CG Scheurlen, W Hasselblatt, M Ligon, KL Kieran, MW Korbel, JO Yaspo, ML Brors, B Felsberg, J Reifenberger, G Collins, VP Jabado, N Eils, R Lichter, P Pfister, SM AF Jones, David T. W. Hutter, Barbara Jaeger, Natalie Korshunov, Andrey Kool, Marcel Warnatz, Hans-Joerg Zichner, Thomas Lambert, Sally R. Ryzhova, Marina Dong Anh Khuong Quang Fontebasso, Adam M. Stuetz, Adrian M. Hutter, Sonja Zuckermann, Marc Sturm, Dominik Gronych, Jan Lasitschka, Baerbel Schmidt, Sabine Seker-Cin, Huriye Witt, Hendrik Sultan, Marc Ralser, Meryem Northcott, Paul A. Hovestadt, Volker Bender, Sebastian Pfaff, Elke Stark, Sebastian Faury, Damien Schwartzentruber, Jeremy Majewski, Jacek Weber, Ursula D. Zapatka, Marc Raeder, Benjamin Schlesner, Matthias Worth, Catherine L. Bartholomae, Cynthia C. von Kalle, Christof Imbusch, Charles D. Radomski, Sylwester Lawerenz, Chris van Sluis, Peter Koster, Jan Volckmann, Richard Versteeg, Rogier Lehrach, Hans Monoranu, Camelia Winkler, Beate Unterberg, Andreas Herold-Mende, Christel Milde, Till Kulozik, Andreas E. Ebinger, Martin Schuhmann, Martin U. Cho, Yoon-Jae Pomeroy, Scott L. von Deimling, Andreas Witt, Olaf Taylor, Michael D. Wolf, Stephan Karajannis, Matthias A. Eberhart, Charles G. Scheurlen, Wolfram Hasselblatt, Martin Ligon, Keith L. Kieran, Mark W. Korbel, Jan O. Yaspo, Marie-Laure Brors, Benedikt Felsberg, Joerg Reifenberger, Guido Collins, V. Peter Jabado, Nada Eils, Roland Lichter, Peter Pfister, Stefan M. CA Int Canc Genome Consortium TI Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma SO NATURE GENETICS LA English DT Article ID MAPK PATHWAY ACTIVATION; ACUTE MYELOID-LEUKEMIA; NEURAL STEM-CELLS; NOONAN-SYNDROME; MUTATIONAL PROCESSES; ONCOGENIC MUTATIONS; SIGNAL-TRANSDUCTION; DISTINCT SUBGROUPS; HUMAN GLIOBLASTOMA; CANCER GENOMES AB Pilocytic astrocytoma, the most common childhood brain tumor(1), is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations(2). Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression(3) and often becoming a chronic disease with substantial morbidities(4). Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing (n = 73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors. New BRAF-activating changes were also observed. MAPK pathway alterations affected all tumors analyzed, with no other significant mutations identified, indicating that pilocytic astrocytoma is predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A-mutated pediatric glioblastoma with additional alterations in the NF1 gene(5). Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma. C1 [Jones, David T. W.; Kool, Marcel; Hutter, Sonja; Sturm, Dominik; Seker-Cin, Huriye; Witt, Hendrik; Northcott, Paul A.; Bender, Sebastian; Pfaff, Elke; Stark, Sebastian; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany. [Hutter, Barbara; Jaeger, Natalie; Schlesner, Matthias; Imbusch, Charles D.; Radomski, Sylwester; Lawerenz, Chris; Brors, Benedikt; Eils, Roland] DKFZ, Div Theoret Bioinformat, Heidelberg, Germany. [Korshunov, Andrey; von Deimling, Andreas] Heidelberg Univ, Dept Neuropathol, Heidelberg, Germany. [Korshunov, Andrey; von Deimling, Andreas] DKFZ, Clin Cooperat Unit Neuropathol, Heidelberg, Germany. [Warnatz, Hans-Joerg; Sultan, Marc; Ralser, Meryem; Worth, Catherine L.; Lehrach, Hans; Yaspo, Marie-Laure] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Zichner, Thomas; Stuetz, Adrian M.; Raeder, Benjamin; Korbel, Jan O.] European Mol Biol Lab, Genome Biol Unit, D-69012 Heidelberg, Germany. [Lambert, Sally R.; Collins, V. Peter] Univ Cambridge, Dept Pathol, Div Mol Histopathol, Cambridge CB2 1QP, England. [Ryzhova, Marina] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow, Russia. [Dong Anh Khuong Quang; Fontebasso, Adam M.; Faury, Damien; Jabado, Nada] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Zuckermann, Marc; Gronych, Jan; Hovestadt, Volker; Weber, Ursula D.; Zapatka, Marc; Lichter, Peter] DKFZ, Div Mol Genet, Heidelberg, Germany. [Lasitschka, Baerbel; Schmidt, Sabine; Wolf, Stephan] DKFZ, Genom & Prote Core Facil, Heidelberg, Germany. [Witt, Hendrik; Milde, Till; Kulozik, Andreas E.; Witt, Olaf; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany. [Schwartzentruber, Jeremy; Majewski, Jacek] McGill Univ, Montreal, PQ, Canada. [Schwartzentruber, Jeremy; Majewski, Jacek] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Bartholomae, Cynthia C.; von Kalle, Christof] DKFZ, Div Translat Oncol, Heidelberg, Germany. [Bartholomae, Cynthia C.; von Kalle, Christof] Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [von Kalle, Christof; Eils, Roland; Lichter, Peter] Heidelberg Ctr Personalised Oncol DKFZ HIPO, Heidelberg, Germany. [Radomski, Sylwester; Eils, Roland] Heidelberg Univ, IPMB, Heidelberg, Germany. [Radomski, Sylwester; Eils, Roland] Heidelberg Univ, BioQuant Ctr, Heidelberg, Germany. [van Sluis, Peter; Koster, Jan; Volckmann, Richard; Versteeg, Rogier] Univ Amsterdam, Amsterdam Med Ctr, Dept Oncogen, Amsterdam, Netherlands. [Monoranu, Camelia] Univ Wurzburg, Inst Pathol, Dept Neuropathol, Wurzburg, Germany. [Winkler, Beate] Childrens Univ Hosp Wurzburg, Dept Pediat Hematol & Oncol, Wurzburg, Germany. [Unterberg, Andreas; Herold-Mende, Christel] Univ Heidelberg Hosp, Dept Neurosurg, Heidelberg, Germany. [Milde, Till; Witt, Olaf] DKFZ, Clin Cooperat Unit Pediat Oncol, Heidelberg, Germany. [Ebinger, Martin] Childrens Univ Hosp, Dept Hematol & Oncol, Tubingen, Germany. [Schuhmann, Martin U.] Univ Hosp, Dept Neurosurg, Tubingen, Germany. [Cho, Yoon-Jae] Stanford Univ, Div Child Neurol, Palo Alto, CA 94304 USA. [Pomeroy, Scott L.; Ligon, Keith L.; Kieran, Mark W.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Pomeroy, Scott L.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Taylor, Michael D.] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada. [Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada. [Karajannis, Matthias A.] NYU, Langone Med Ctr, Hassenfeld Childrens Ctr Canc & Blood Disorders, New York, NY USA. [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Div Pathol, Baltimore, MD USA. [Scheurlen, Wolfram] Nurnberg Childrens Hosp, Cnopfsche Kinderklin, Nurnberg, Germany. [Hasselblatt, Martin] Univ Hosp Munster, Inst Neuropathol, Munster, Germany. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Felsberg, Joerg; Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany. [Jabado, Nada] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Paediat, Montreal, PQ H3H 1P3, Canada. RP Eils, R (reprint author), DKFZ, Div Theoret Bioinformat, Heidelberg, Germany. EM r.eils@dkfz-heidelberg.de; m.macleod@dkfz-heidelberg.de; s.pfister@dkfz-heidelberg.de RI Waha, Andreas/J-2950-2014; Schlesner, Matthias/I-4030-2013; Milde, Till/L-7755-2015; Witt, Hendrik/L-7810-2015; Eils, Roland/B-6121-2009; Pfister, Stefan/F-6860-2013; Ebinger, Martin/O-4936-2016; Korbel, Jan/G-6470-2012; Kool, Marcel/H-2541-2013; Brors, Benedikt/E-5620-2013; von Deimling, Andreas/F-7774-2013; OI Warnatz, Hans-Jorg/0000-0002-0327-9209; Kieran, Mark/0000-0003-2184-7692; Hutter, Barbara/0000-0002-9034-0329; Karajannis, Matthias/0000-0002-7151-6528; Sturm, Dominik/0000-0003-0250-1696; Schwartzentruber, Jeremy/0000-0002-6183-2092; Hovestadt, Volker/0000-0002-3480-6649; Hasselblatt, Martin/0000-0003-2707-8484; Raeder, Benjamin/0000-0002-9494-8884; Schlesner, Matthias/0000-0002-5896-4086; Eils, Roland/0000-0002-0034-4036; Pfister, Stefan/0000-0002-5447-5322; Ebinger, Martin/0000-0002-4229-8058; Korbel, Jan/0000-0002-2798-3794; Brors, Benedikt/0000-0001-5940-3101; von Deimling, Andreas/0000-0002-5863-540X; Jaeger, Natalie/0000-0002-9589-7580; Stuetz, Adrian/0000-0001-7650-3470; Zichner, Thomas/0000-0001-9848-7598 FU German Cancer Aid [109252]; German Federal Ministry of Education and Research (BMBF) [01KU1201A, MedSys 0315416C, NGFNplus 01GS0883]; German Cancer Research Center-Heidelberg Center for Personalized Oncology (DKFZ-HIPO); Max Planck Society, Genome Canada; Canadian Institute for Health Research (CIHR); Genome BC; Genome Quebec; CIHR-ICR (Institute for Cancer Research); C17; Ian's Friend Foundation; US National Institutes of Health (NIH) [RO1CA105607, P30HD018655]; Dutch Cancer Foundations KWF [2010-4713]; KIKA; Brain Tumour Charity; Pediatric Low-Grade Astrocytoma Foundation FX For technical support and expertise, we thank B. Haase, D. Pavlinic and B. Baying (EMBL Genomics Core Facility); M. Wahlers and R. Luck (EMBL High-Performance Computing Facility); the DKFZ Genomics and Proteomics Core Facility; M. Knopf (NCT Heidelberg); K. Schlangen, M. Metsger, K. Schulz, A. Nurnberger, A. Kovacsovics and M. Linser (Max Planck Institute for Molecular Genetics); S. Peetz-Dienhart and Y. Floer (University Hospital Munster); D. M. Pearson (University of Cambridge); and B. Huang, G. Zipprich, M. Heinold, R. Kabbe, A. Wittmann, L. Sieber and L. Linke (DKFZ). W. Stummer (Munster), B. Hoffmann (Munster), B. Rama (Osnabruck), H. Ebel (Hamm), H. A. Trost (Bayreuth) and U. Wildforster (Gelsenkirchen) provided detailed clinical information. We also thank GATC Biotech for sequencing services. This work was principally supported by the PedBrain Tumor Project contributing to the International Cancer Genome Consortium, funded by German Cancer Aid (109252) and by the German Federal Ministry of Education and Research (BMBF, grants 01KU1201A, MedSys 0315416C and NGFNplus 01GS0883). Additional support came from the German Cancer Research Center-Heidelberg Center for Personalized Oncology (DKFZ-HIPO), the Max Planck Society, Genome Canada and the Canadian Institute for Health Research (CIHR) with cofunding from Genome BC, Genome Quebec, CIHR-ICR (Institute for Cancer Research) and C17 (N. Jabado), Ian's Friend Foundation (M. A. K.), the US National Institutes of Health (NIH; grants RO1CA105607 and P30HD018655 to S. L. P.), the Dutch Cancer Foundations KWF (2010-4713) and KIKA (M. K.), the Brain Tumour Charity (S. R. L. and V. P. C.) and the Pediatric Low-Grade Astrocytoma Foundation (M. W. K. and K.L.L.). NR 78 TC 158 Z9 162 U1 3 U2 31 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 AUG PY 2013 VL 45 IS 8 BP 927 EP U295 DI 10.1038/ng.2682 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 190WW UT WOS:000322374900018 PM 23817572 ER PT J AU Shlipak, MG Day, EC AF Shlipak, Michael G. Day, Erica C. TI Biomarkers for incident CKD: a new framework for interpreting the literature SO NATURE REVIEWS NEPHROLOGY LA English DT Review ID CHRONIC KIDNEY-DISEASE; ATHEROSCLEROSIS MESA; PREDICTION MODELS; TREFOIL FACTOR-3; FUNCTION DECLINE; URINARY LEVELS; RISK; APOL1; NEPHROPATHY; VARIANTS AB Biomarkers are a useful tool for the investigation of chronic kidney disease (CKD), although the design, analytical tools and outcomes used in many biomarker studies are suboptimal. In part, this situation might reflect a lack of appreciation of the nature of different biomarkers. A particular biomarker could, for example, be implicated in the pathogenesis of CKD because it is a physiological risk factor for declining kidney function, an indicator of impaired kidney function, or a marker of ongoing injury within the kidney. Such risk factors enable us to understand the process of disease and to identify treatment targets. By contrast, risk markers enable us to distinguish persons who will or will not develop CKD, even though the markers themselves are not required to be modifiable by (or directly involved in) the disease process. Accurate prediction of CKD risk will probably require a combination of biomarkers of several types, however. This Review offers a conceptual framework for interpreting the results of studies evaluating biomarkers of declining kidney function and incident CKD. C1 [Shlipak, Michael G.; Day, Erica C.] San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. RP Shlipak, MG (reprint author), San Francisco Vet Adm Med Ctr, 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU National Institutes of Health, Bethesda, MD, USA [5R01AG034853-04, 5R01AG027002-07, 5R01DK087961-02] FX The authors acknowledge research grant support (M. G. Shlipak as principal investigator) from the National Institutes of Health, Bethesda, MD, USA (5R01AG034853-04; 5R01AG027002-07; 5R01DK087961-02). NR 33 TC 7 Z9 7 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD AUG PY 2013 VL 9 IS 8 BP 478 EP 483 DI 10.1038/nrneph.2013.108 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 190EL UT WOS:000322321700009 PM 23752888 ER PT J AU van Eeghen, AM Teran, LO Johnson, J Pulsifer, MB Thiele, EA Caruso, P AF van Eeghen, Agnies M. Teran, Laura Ortiz Johnson, Jason Pulsifer, Margaret B. Thiele, Elizabeth A. Caruso, Paul TI The neuroanatomical phenotype of tuberous sclerosis complex: focus on radial migration lines SO NEURORADIOLOGY LA English DT Article DE Tuberous sclerosis complex; DTI; Radial migration lines; Cognition; Epilepsy ID WHITE-MATTER; MRI FINDINGS; BRAIN; EPILEPSY; AUTISM; ABNORMALITIES; CHILDREN; IDENTIFICATION; MALFORMATIONS; IMPAIRMENT AB The contribution of radial migration lines (RMLs) to the neuroanatomical and neurocognitive phenotype of tuberous sclerosis complex (TSC) is unclear. The aim of this study was to perform a comprehensive evaluation of the neuroradiological phenotype of TSC, distinguishing RMLs from normal-appearing white matter (NAWM) using diffusion tensor imaging (DTI) and volumetric fluid-attenuated inversion recovery imaging. Magnetic resonance images of 30 patients with TSC were evaluated. The frequencies of RMLs, tubers, and subependymal nodules (SENs) were determined for every hemispheric lobe. Cerebellar lesions and subependymal giant cell tumors were counted. DTI metrics were obtained from the NAWM of every hemispheric lobe and from the largest RML and tuber. Analyses of variance and correlations were performed to investigate the associations between neuroanatomical characteristics and relationships between RML frequency and neurocognitive outcomes. NAWM DTI metrics were compared with measurements of 16 control patients. A mean of 47 RMLs, 27 tubers, and 10 SENs were found per patient, and the frequencies of these lesions were strongly correlated (p < 0.001). RML fractional anisotropy and mean diffusivity were strongly inversely correlated (p = 0.003). NAWM DTI metrics were similar to the controls (p = 0.26). RML frequency was strongly associated with age of seizure onset (p = 0.003), intelligence outcomes (p = 0.01), and level of autistic features (p = 0.007). A detailed neuroradiological phenotype is presented, showing that RMLs are the most frequent neuroanatomical lesion, are responsible for white matter DTI abnormalities, and are strongly associated with age of seizure onset, intelligence outcomes, and level of autistic features. C1 [van Eeghen, Agnies M.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. [van Eeghen, Agnies M.] Erasmus MC, Expertise Ctr Neurodev Disorders, ENCORE, Dept Neurosci, Rotterdam, Netherlands. [Teran, Laura Ortiz; Johnson, Jason; Caruso, Paul] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA. RP van Eeghen, AM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, 175 Cambridge St, Boston, MA 02114 USA. EM avaneeghen@partners.org FU Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01 NS024279] FX We are grateful for the consent of the patients and for the thorough reading of the manuscript by Susana Boronat, M. D. This study was funded by the Herscot Center for Tuberous Sclerosis Complex and NIH/NINDS P01 NS024279. NR 41 TC 13 Z9 13 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD AUG PY 2013 VL 55 IS 8 BP 1007 EP 1014 DI 10.1007/s00234-013-1184-3 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 186CZ UT WOS:000322020900012 PM 23644537 ER PT J AU Hart, JE Garshick, E Smith, TJ Davis, ME Laden, F AF Hart, Jaime E. Garshick, Eric Smith, Thomas J. Davis, Mary E. Laden, Francine TI Ischaemic heart disease mortality and years of work in trucking industry workers SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE Vehicle emissions; diesel exhaust; cardiovascular disease; cancer; public health; epidemiology; transport; particulates; health and safety; retrospective exposure assessment; statistics; exposure assessment; air pollution ID PARTICULATE MATTER EXPOSURE; LONG-TERM EXPOSURE; AMBIENT AIR-POLLUTION; MYOCARDIAL-INFARCTION; HOSPITAL ADMISSIONS; LUNG-CANCER; OCCUPATIONAL-EXPOSURE; DIESEL EXHAUST; US CITIES; MALE BUS AB Objectives Evidence from general population-based studies and occupational cohorts has identified air pollution from mobile sources as a risk factor for cardiovascular disease. In a cohort of US trucking industry workers, with regular exposure to vehicle exhaust, the authors previously observed elevated standardised mortality ratios for ischaemic heart disease (IHD) compared with members of the general US population. Therefore, the authors examined the association of increasing years of work in jobs with vehicle exhaust exposure and IHD mortality within the cohort. Methods The authors calculated years of work in eight job groups for 30?758 workers using work records from four nationwide companies. Proportional hazard regression was used to examine relationships between IHD mortality, 1985-2000, and employment duration in each job group. Results HRs for at least 1year of work in each job were elevated for dockworkers, long haul drivers, pick-up and delivery drivers, combination workers, hostlers, and shop workers. There was a suggestion of an increased risk of IHD mortality with increasing years of work as a long haul driver, pick-up and delivery driver, combination worker, and dockworker. Conclusion These results suggest an elevated risk of IHD mortality in workers with a previous history of regular exposure to vehicle exhaust. C1 [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hart, Jaime E.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Smith, Thomas J.; Davis, Mary E.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Davis, Mary E.] Tufts Univ, Dept Urban & Environm Policy & Planning, Medford, MA 02155 USA. RP Hart, JE (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM jaime.hart@channing.harvard.edu FU NIH/NCI [R01 CA90792]; NIEHS [ES00002] FX This study was supported by NIH/NCI R01 CA90792; NIEHS ES00002. NR 51 TC 7 Z9 7 U1 1 U2 18 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD AUG PY 2013 VL 70 IS 8 BP 523 EP 528 DI 10.1136/oemed-2011-100017 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 187JR UT WOS:000322114400002 PM 22992341 ER PT J AU Ning, MM Lo, EH Ning, PC Xu, SY McMullin, D Demirjian, Z Inglessis, I Dec, GW Palacios, I Buonanno, FS AF Ning, MingMing Lo, Eng H. Ning, Pei-Chen Xu, Su-Yu McMullin, David Demirjian, Zareh Inglessis, Ignacio Dec, G. William Palacios, Igor Buonanno, Ferdinando S. TI The brain's heart - Therapeutic opportunities for patent foramen ovale (PFO) and neurovascular disease SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Patent foramen ovate; PFO; Stroke; Migraine; CLOSURE I trial; RESPECT trial; Neurovascular injury; Serotonin (5-HT) ID TO-LEFT SHUNT; ATRIAL SEPTAL ANEURYSM; ISCHEMIC-STROKE SUBTYPES; OBSTRUCTIVE SLEEP-APNEA; CONTRAST-TRANSCRANIAL DOPPLER; FACTOR-V-LEIDEN; PERCUTANEOUS TRANSCATHETER CLOSURE; MIGRAINE HEADACHE RELIEF; MAY-THURNER-SYNDROME; TERM-FOLLOW-UP AB Patent foramen ovale (PFO), a common congenital cardiac abnormality, is a connection between the right and left atria in the heart. As a "back door to the brain", PFO can serve as a conduit for paradoxical embolism, allowing venous thrombi to enter the arterial circulation, avoiding filtration by the lungs, and causing ischemic stroke. PFO-related strokes affect more than 150,000 people per year in the US, and PFO is present in up to 60% of migraine patients with aura, and in one out of four normal individuals. So, in such a highly prevalent condition, what are the best treatment and prevention strategies? Emerging studies show PFO-related neurovascular disease to be a multi-organ condition with varying individual risk factors that may require individualized therapeutic approaches - opening the field for new pharmacologic and therapeutic targets. The anatomy of PFO suggests that, in addition to thrombi, it can also allow harmful circulatory factors to travel directly from the venous to the arterial circulation, a concept important in finding novel therapeutic targets for PFO-related neurovascular injury. Here, we: 1) review emerging data on PFO-related injuries and clinical trials; 2) discuss potential mechanisms of PFO-related neurovascular disease in the context of multi-organ interaction and heart-brain signaling; and 3) discuss novel therapeutic targets and research frontiers. Clinical studies and molecular mapping of the circulatory landscape of this multi-organ disease will both be necessary in order to better individualize clinical treatment for a condition affecting more than a quarter of the world's population. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ning, MingMing; Lo, Eng H.; Ning, Pei-Chen; Xu, Su-Yu; McMullin, David; Demirjian, Zareh; Inglessis, Ignacio; Palacios, Igor; Buonanno, Ferdinando S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardio Neurol Clin, Boston, MA 02114 USA. [Ning, MingMing; Lo, Eng H.; Ning, Pei-Chen; Xu, Su-Yu; McMullin, David; Buonanno, Ferdinando S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Prote Res Ctr, Boston, MA 02114 USA. [Ning, MingMing; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neuroprotect Res Lab, Boston, MA 02114 USA. [Demirjian, Zareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol, Boston, MA 02114 USA. [Inglessis, Ignacio; Dec, G. William; Palacios, Igor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA 02114 USA. RP Ning, MM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Cardio Neurol Clin, ACC-739C,55 Fruit St, Boston, MA 02114 USA. EM ning@hms.harvard.edu FU NIH/NINDS [R01- NS067139, R21-NS52498, R37-NS37074, P01-NS55104] FX Supported in part by the NIH/NINDS: R01- NS067139(Ning), R21-NS52498 (Ning), R37-NS37074(Lo), P01-NS55104(Lo). NR 173 TC 10 Z9 11 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD AUG PY 2013 VL 139 IS 2 BP 111 EP 123 DI 10.1016/j.pharmthera.2013.03.007 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 187DX UT WOS:000322098200002 PM 23528225 ER PT J AU Loftis, JM Huckans, M AF Loftis, Jennifer M. Huckans, Marilyn TI Substance use disorders: Psychoneuroimmunological mechanisms and new targets for therapy SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Addiction; Drug discovery; Inflammation; Psychoneuroimmunology; Substance use disorders; Treatment strategies ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RANDOMIZED CONTROLLED-TRIAL; ALCOHOL-DEPENDENT PATIENTS; PITUITARY-ADRENAL AXIS; TUMOR-NECROSIS-FACTOR; KILLER-CELL-ACTIVITY; HEPATITIS-C VIRUS; ETHANOL EXPOSURE; DRUG-ABUSE; METHAMPHETAMINE DEPENDENCE AB An estimated 76.4 million people worldwide meet criteria for alcohol use disorders, and 15.3 million meet criteria for drug use disorders. Given the high rates of addiction and the associated health, economic, and social costs, it is essential to develop a thorough understanding of the impact of substance abuse on mental and physical health outcomes and to identify new treatment approaches for substance use disorders (SUDs). Psychoneuroimmunology is a rapidly expanding, multidisciplinary area of research that may be of particular importance to addiction medicine, as its focus is on the dynamic and complex interactions among behavioral factors, the central nervous system, and the endocrine and immune systems (Ader, 2001). This review, therefore, focuses on: 1) the psychoneuroimmunologic effects of SUDs by substance type and use pattern, and 2) the current and future treatment strategies, including barriers that can impede successful recovery outcomes. Evidence-based psychosocial and pharmacotherapeutic treatments are reviewed. Psychological factors and central nervous system correlates that impact treatment adherence and response are discussed. Several novel therapeutic approaches that are currently under investigation are introduced; translational data from animal and human studies is presented, highlighting immunotherapy as a promising new direction for addiction medicine. Published by Elsevier Inc. C1 [Loftis, Jennifer M.; Huckans, Marilyn] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. [Huckans, Marilyn] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Loftis, Jennifer M.; Huckans, Marilyn] Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97201 USA. [Loftis, Jennifer M.; Huckans, Marilyn] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97201 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM loftisj@ohsu.edu; Jennifer.loftis2@va.gov FU NIDA/NIH [DA018165] FX This work was in part supported by NIDA/NIH grant DA018165 to the Methamphetamine Abuse Research Center (MARC) in Portland, Oregon. This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center and Oregon Health 82 Sciences University. NR 158 TC 8 Z9 8 U1 0 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD AUG PY 2013 VL 139 IS 2 BP 289 EP 300 DI 10.1016/j.pharmthera.2013.04.011 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 187DX UT WOS:000322098200009 PM 23631821 ER PT J AU Raff, H Brown, D AF Raff, Hershel Brown, Dennis TI Civil, sensible, and constructive peer review in APS journals SO PHYSIOLOGICAL GENOMICS LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; QUALITY C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Raff, Hershel] Aurora Res Fdn, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI USA. [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Raff, H (reprint author), Aurora St Lukes Med Ctr, 2801 W KK River Pky,Ste 245, Milwaukee, WI 53215 USA. EM hraff@mcw.edu NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD AUG PY 2013 VL 45 IS 15 BP 629 EP 630 DI 10.1152/physiolgenomics.00080.2013 PG 2 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 193MW UT WOS:000322564900001 PM 23695886 ER PT J AU Wang, JH AF Wang, Jia-Huai TI The sequence signature of an Ig-fold SO PROTEIN & CELL LA English DT Article ID CELL-ADHESION MOLECULES; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; SUPERFAMILY; SPECIFICITY; RESOLUTION; PROTEINS; ELEGANS; DOMAINS; COMPLEX AB Ig superfamily (IgSF) constitutes the largest superfamily in human genome. In particular, Ig-like domains are the most abundant structural module within cell surface receptors, functioning in nervous as well as immune system. Here I describe some key sequence signature of an I-set Ig-like domain from known structures of IgSF members. These signature residues define the I-set Ig-like domain, which should aid structural and functional studies of cell surface receptors. C1 [Wang, Jia-Huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Jia-Huai] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu FU NIH; Ministry of Education of China FX This work has been supported by NIH grants and the support from the Ministry of Education of China. NR 25 TC 2 Z9 2 U1 0 U2 2 PU HIGHER EDUCATION PRESS PI BEIJING PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA SN 1674-800X J9 PROTEIN CELL JI Protein Cell PD AUG PY 2013 VL 4 IS 8 BP 569 EP 572 DI 10.1007/s13238-013-3903-2 PG 4 WC Cell Biology SC Cell Biology GA 191DZ UT WOS:000322394300003 PM 23842991 ER PT J AU Ach, E Gerhardt, CA Barrera, M Kupst, MJ Meyer, EA Patenaude, AF Vannatta, K AF Ach, Emily Gerhardt, Cynthia A. Barrera, Maru Kupst, Mary Jo Meyer, Eugene A. Patenaude, Andrea F. Vannatta, Kathryn TI Family factors associated with academic achievement deficits in pediatric brain tumor survivors SO PSYCHO-ONCOLOGY LA English DT Article DE brain tumors; childhood; survivors; family environment; academic achievement; demographics ID CHILDHOOD-CANCER SURVIVORS; LONG-TERM SURVIVORS; NEUROCOGNITIVE SEQUELAE; CHILDREN; INJURY; BEHAVIOR; OUTCOMES; MEDULLOBLASTOMA; METAANALYSIS; ADOLESCENCE AB Purpose The purpose of this study is to examine whether parental education, socioeconomic status, or family environment moderate the extent of academic achievement deficits in pediatric brain tumor survivors (PBTS) relative to classmate case-controls. PBTS are known to be at risk for cognitive and academic impairment; however, the degree of impairment varies. Prior research has focused on treatment risk, and efforts to examine the protective role of family resources and relationships have been lacking. Methods Pediatric brain tumor survivors (N=164), ages 8-15 and 1-5years posttreatment, were recruited at five treatment centers in the United States and Canada. A case-control classmate, matched for age, gender, and race, was recruited for each survivor. The Wide Range Achievement Test, a demographic form, and the Family Environment Scale were administered in families' homes. Treatment data were abstracted from medical charts. Results Pediatric brain tumor survivors demonstrated lower achievement than classmate-controls in reading, spelling, and arithmetic. Parental education and socioeconomic status were associated with levels of achievement demonstrated by PBTS but did not account for discrepancies between PBTS and classmate-controls. Deficits in achievement relative to classmate-controls, across all academic domains, were greater for survivors in families lower in support and higher in conflict. These associations remained after controlling for age at diagnosis, time since treatment, and whether treatment had involved chemotherapy, focal, or whole brain radiation. Conclusions These results support the development of interventions to enhance family functioning as well as educational resources as part of intervention and rehabilitation services to optimize academic progress in children who have been treated for brain tumors. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Ach, Emily; Gerhardt, Cynthia A.; Vannatta, Kathryn] Childrens Hosp, Inst Nationwide, Columbus, OH 43205 USA. [Ach, Emily; Gerhardt, Cynthia A.; Vannatta, Kathryn] Ohio State Univ, Columbus, OH 43210 USA. [Barrera, Maru] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Kupst, Mary Jo] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Kupst, Mary Jo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Meyer, Eugene A.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. [Patenaude, Andrea F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Patenaude, Andrea F.] Harvard Univ, Sch Med, Boston, MA USA. RP Vannatta, K (reprint author), Childrens Hosp, Inst Nationwide, Ctr Biobehav Hlth, 700 Childrens Dr, Columbus, OH 43205 USA. EM Kathryn.Vannatta@nationwidechildrens.org RI Gerhardt, Cynthia/E-3109-2011; Vannatta, Kathryn/E-4237-2011 FU American Cancer Society [RSGPB-03-098-01-PBP]; National Cancer Institute [RO3 CA097740-02] FX This work was supported by awards from the American Cancer Society (RSGPB-03-098-01-PBP) and the National Cancer Institute (RO3 CA097740-02). NR 41 TC 12 Z9 12 U1 3 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD AUG PY 2013 VL 22 IS 8 BP 1731 EP 1737 DI 10.1002/pon.3202 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 186CP UT WOS:000322019800006 PM 23059621 ER PT J AU Kumar, AR Schapira, L AF Kumar, Anisha Rajeev Schapira, Lidia TI The impact of intrapersonal, interpersonal, and community factors on the identity formation of young adults with cancer: a qualitative study SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; young adults; identity; coping; normalcy ID OF-LIFE; CHILDHOOD-CANCER; PSYCHOSOCIAL CARE; SUPPORT GROUPS; SURVIVORS; ADOLESCENT AB Background The purpose of this study was to examine how young adult cancer patients make sense of their experiences with cancer. Methods Semi-structured interviews were conducted with patients at an urban tertiary care center Results The sample for this study included 15 young adult cancer survivors. The ages of the participants ranged from 18 to 30years. The sample was 67% female (n=10) and 33% male (n=5). The sample was 87% Caucasian (n=13) and 13% Hispanic (n=2). Fifty-three percent of the participants were between ages 18 and 23years (n=8), and 47% of the participants were between ages 24 and 30years (n=7). Three themes emerged from the data: intrapersonal change, interpersonal interactions, and role and identity in the hospital and the community. As they inevitably lose control in their lives, young adult patients seek to return to a familiar lifestyle that they consider as normal'. The formation of a revised identity and redefined set of norms allows the patients to regain control and express their individualism. Conclusions This study contributes to our knowledge of the experiences of young adult cancer patients and survivors. The findings serve to inform young adults, caregivers, and health professionals on coping with illness and its aftermath. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Kumar, Anisha Rajeev] Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. RP Kumar, AR (reprint author), Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. EM arkumar@post.harvard.edu FU Harvard College Research Program; Cordeiro Health Policy Summer Research Grant FX This research would not have been possible without the generous participation of the young adult patients and the immense support of the medical staff of the MGH Cancer Center. We greatly appreciate the thoughtful comments and constructive insight of Dr. Arthur Kleinman of the Department of Anthropology at Harvard University. We are also grateful to the Harvard College Research Program and the Cordeiro Health Policy Summer Research Grant for generously funding this research. NR 36 TC 5 Z9 5 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD AUG PY 2013 VL 22 IS 8 BP 1753 EP 1758 DI 10.1002/pon.3207 PG 6 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 186CP UT WOS:000322019800009 PM 23080480 ER PT J AU Rosenberg, SM Tamimi, RM Gelber, S Ruddy, KJ Kereakoglow, S Borges, VF Come, SE Schapira, L Winer, EP Partridge, AH AF Rosenberg, Shoshana M. Tamimi, Rulla M. Gelber, Shari Ruddy, Kathryn J. Kereakoglow, Sandra Borges, Virginia F. Come, Steven E. Schapira, Lidia Winer, Eric P. Partridge, Ann H. TI Body image in recently diagnosed young women with early breast cancer SO PSYCHO-ONCOLOGY LA English DT Article DE breast cancer; oncology; young women; body image; mastectomy ID QUALITY-OF-LIFE; CONTRALATERAL PROPHYLACTIC MASTECTOMY; PSYCHOSOCIAL ADJUSTMENT; PSYCHOLOGICAL IMPACT; CONSERVING SURGERY; WEIGHT-GAIN; RECONSTRUCTION; LYMPHEDEMA; SURVIVORS; HEALTH AB Objective To assess body image concerns among young women following a breast cancer diagnosis. Methods A total of 419 women with recently diagnosed stage 0-III breast cancer were surveyed following enrollment as part of a prospective cohort study of women age 40 or younger at diagnosis. Body image was assessed using three items from the psycho-social scale of the Cancer Rehabilitation Evaluation System (CARES). CARES scores range from 0 to 4, with higher scores indicative of greater image concerns. Mean CARES scores were calculated and compared between treatment groups using t-tests and analysis of variance. Multiple linear regression models were fit to evaluate the relationship between physical and psychological factors and body image. Results Mean time from diagnosis to completion of the baseline survey was 5.2months. The mean CARES score for all women was 1.28. Mean CARES scores in the mastectomy-only group (1.87) and in the mastectomy with reconstruction group (1.52) were significantly higher (p<0.0001) compared with the scores in the lumpectomy group (0.85), indicating that radical surgery was associated with more body image concerns. Radiation (p=0.01), anxiety (p=0.0001), depression (p<0.0001), fatigue (p=0.04), musculoskeletal pain symptoms (p<0.0001), weight gain (p=0.01), and weight loss (p=0.02), in addition to surgery type (p<0.0001), were all associated with more body image concerns in the multi-variable analysis. Conclusion This analysis highlights the impact of treatment, along with physical and psychological factors, on body image early in the survivorship period. Our findings provide targets for potential future intervention and may aid young women in the surgical decision-making process. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Rosenberg, Shoshana M.; Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Tamimi, Rulla M.; Ruddy, Kathryn J.; Come, Steven E.; Schapira, Lidia; Winer, Eric P.; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. [Gelber, Shari; Ruddy, Kathryn J.; Kereakoglow, Sandra; Winer, Eric P.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Borges, Virginia F.] Univ Colorado, Denver, CO 80202 USA. [Come, Steven E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ahpartridge@partners.org FU Susan G. Komen for the Cure; NIH [R25 CA92203] FX This work was supported by Susan G. Komen for the Cure and NIH R25 CA92203. NR 53 TC 32 Z9 35 U1 1 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD AUG PY 2013 VL 22 IS 8 BP 1849 EP 1855 DI 10.1002/pon.3221 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 186CP UT WOS:000322019800022 PM 23132765 ER PT J AU Linos, D Kiriakopoulos, A Petralias, A AF Linos, Dimitrios Kiriakopoulos, Andreas Petralias, Athanassios TI Patient Attitudes toward Transaxillary Robot-assisted Thyroidectomy SO WORLD JOURNAL OF SURGERY LA English DT Article ID SCAR ASSESSMENT QUESTIONNAIRE; SF-36 HEALTH SURVEY; PARATHYROID SURGERY; ENDOSCOPIC THYROIDECTOMY; INITIAL-EXPERIENCE; IQOLA PROJECT; MANAGEMENT; CARCINOMA; GASLESS AB The transaxillary robot-assisted technique constitutes an acceptable treatment option for patients requiring thyroidectomy. However, patients' attitudes toward this new technique have not yet been analyzed. A sample of 596 randomly selected patients who underwent thyroidectomy between January 2000 and March 2010 was assessed. We evaluated patients' attitudes toward transaxillary robot-assisted thyroidectomy, taking into account the validated Patient Scar Assessment Questionnaire, the SF-36 Health Survey Questionnaire, and 11 sociodemographic and surgical patient characteristics. Only 11.6 % of the patients would prefer to have been treated with the transaxillary method. Most patients had concerns that it would be a more painful procedure (39.2 %), and they expressed satisfaction with the existing esthetic outcome (29.1 %); other concerns were that the robotic approach would be of longer duration (25.4 %) and at higher cost (15.5 %). Nevertheless, the worse the appearance of the neck scar the more preferable is the new method (p = 0.025), a result that holds true irrespective of patients' physical health, the invasive procedure attained (conventional or minimal), and the presence of postoperative complications, among other characteristics. Patients diagnosed with a benign or uncertain neoplasm (p = 0.022) and younger patients (p = 0.003) held a more positive view of the new method. Patients who have undergone conventional thyroidectomy via the usual neck incision do not express a preference for the transaxillary method. The reasons given include various perceived disadvantages of the robotic procedure (increased pain, longer operative times, and higher cost). Younger patients, patients with poor appearance of their neck scar, and patients with benign thyroid pathology seem to hold a more positive attitude toward the robotic approach. C1 [Linos, Dimitrios] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Linos, Dimitrios; Kiriakopoulos, Andreas] Hygeia Hosp, Dept Surg, Athens, Greece. [Linos, Dimitrios] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Petralias, Athanassios] Athens Univ Econ & Business, Dept Stat, Athens, Greece. RP Linos, D (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dlinos@hms.harvard.edu NR 31 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD AUG PY 2013 VL 37 IS 8 BP 1959 EP 1965 DI 10.1007/s00268-013-2090-x PG 7 WC Surgery SC Surgery GA 186EA UT WOS:000322023600030 PM 23665817 ER PT J AU Engel, LC Lee, AM Seifarth, H Sidhu, MS Brady, TJ Hoffmann, U Ghoshhajra, BB AF Engel, Leif-Christopher Lee, Ashley Mingshin Seifarth, Harald Sidhu, Manavjot S. Brady, Thomas J. Hoffmann, Udo Ghoshhajra, Brian B. TI Weekly Dose Reports: The Effects of a Continuous Quality Improvement Initiative on Coronary Computed Tomography Angiography Radiation Doses at a Tertiary Medical Center SO ACADEMIC RADIOLOGY LA English DT Article DE Coronary CT angiography; radiation dose; quality improvement; process improvement ID TUBE POTENTIAL SELECTION; PITCH SPIRAL ACQUISITION; ACUTE CHEST-PAIN; DUAL-SOURCE CT; TOMOGRAPHY ANGIOGRAPHY; IMAGE-QUALITY; RADIATION-EXPOSURE; SHOOT MODE; REDUCTION; PROTOCOL AB Rationale and Objectives: Numerous protocols have been developed to reduce cardiac computed tomography angiography (cCTA) radiation dose while maintaining image quality. However, cCTA practice is highly dependent on physician and technologist experience and education. In this study, we sought to evaluate the incremental value of real-time feedback via weekly dose reports on a busy cCTA service. Materials and Methods: This time series analysis consisted of 450 consecutive patients whom underwent physician-supervised cCTA for clinically indicated native coronary evaluation between April 2011 and January 2013, with 150 patients before the initiation of weekly dose report (preintervention period: April-September 2011) and 150 patients after the initiation (postintervention period: September 2011-February 2012). To assess whether overall dose reductions were maintained over time, results were compared to a late control group consisting of 150 consecutive cCTA exams, which were performed after the study (September 2012-January 2013). Patient characteristics and effective radiation were recorded and compared. Results: Total radiation dose was significantly lower in the postintervention period (3.4 mSv [1.7-5.7] and in the late control group (3.3 mSv [2.0-5.3] versus the preintervention period (4.1 mSv [2.1-6.6] (P = .005). The proportion of high-dose outliers was also decreased in the postintervention period and late control period (exams <10 mSv were 88.0% preintervention vs. 97.3% postintervention vs. 95.3% late control; exams <15 mSv were 98.0% preintervention vs. 100.0% postintervention vs. 98.7% late control; exams <20.0 mSv were 98.7% preintervention vs. 100.0% postintervention vs. 100.0% late control). Conclusion: Weekly dose report feedback of site radiation doses to patients undergoing physician-supervised cCTA resulted in significant overall dose reduction and reduction of high-dose outliers. Overall dose reductions were maintained beyond the initial study period. C1 [Lee, Ashley Mingshin] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee, AM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM lithiumbromide@gmail.com NR 33 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 2013 VL 20 IS 8 BP 1015 EP 1023 DI 10.1016/j.acra.2013.04.012 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187DS UT WOS:000322097700014 PM 23830607 ER EF